PMID- 1283462 TI - Neonatal capsaicin treatment prevents the development of the thermal hyperalgesia produced in a model of neuropathic pain in the rat. AB - Loose ligation of the sciatic nerve with 4-0 chromic gut sutures in rats produces behavioral evidence of neuropathic pain. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating the thermal hyperalgesia produced by this model. Male Sprague-Dawley rats, treated as neonates (within 48 h of birth) with capsaicin (50 mg/kg, s.c.) or vehicle, were used at 16-18 weeks of age. Chromic gut sutures (4-0) were tied around the left sciatic nerve and withdrawal latencies of both hind paws to radiant heat were determined on postoperative days 3, 5, 10 and 20. Whereas there was a pronounced thermal hyperalgesia which lasted for up to 20 days in vehicle-treated rats, there was no evidence of thermal hyperalgesia in capsaicin-treated rats. There was no difference in baseline (pre-surgery) withdrawal latencies between the two groups. Radioimmunoassay revealed that there was a significant depletion of substance P (43.8%) and calcitonin-gene-related peptide (72.6%) in the lumbar spinal cord of neonatal capsaicin-treated rats compared to vehicle-treated rats. These results demonstrate that the chromic gut-induced thermal hyperalgesia is mediated by capsaicin-sensitive afferents and suggest that central mechanisms which process and control the reflex response to heat are different than mechanisms involved in thermal hyperalgesia. PMID- 1283463 TI - The course of HBV overinfection during NANB CAH in treatment with IFN. PMID- 1283464 TI - Purification and characterization of the major cationic kallikrein inhibitor in bovine pituitary gland. AB - The presence of two types of kallikrein inhibitor (cationic and anionic inhibitors) was demonstrated in bovine pituitary gland. These kallikrein inhibitors were separated from the homogenate of bovine posterior pituitary by successive CM-Sephadex chromatography. The major cationic inhibitor was further purified to homogeneity by affinity chromatography using porcine pancreatic beta kallikrein immobilized on Sepharose 4B and gel filtration. The complete amino acid sequence of this inhibitor was first determined, and it was shown to be a peptide of 58 residues with a calculated molecular weight of 6,511. The Ki value against bovine pituitary kallikrein was 6 x 10(-9) M. The cationic inhibitor was found to be identical with basic pancreatic trypsin inhibitor. PMID- 1283465 TI - Immunohistochemical localization of PGF2 alpha receptor in the mouse testis. AB - As a step towards understanding the role of prostaglandin F2 alpha (PGF2 alpha) in male reproductive tract physiology, a rabbit polyclonal antiserum reactive with purified PGF2 alpha receptor (PGF2 alpha-R) was produced. Here we describe the use of this anti-PGF2 alpha-R antiserum in immunohistochemical staining of mouse testis to ascertain which cell types, in vivo, possess immunoreactive PGF2 alpha-R. As an initial control Western blot analysis was performed to show that the anti-PGF2 alpha-R antiserum recognizes only one antigen in the testis, and that this molecule is similar in molecular mass (by PAGE) to the previously described, purified PGF2 alpha-R molecule. Immunohistochemical staining demonstrates that adult mouse testis contains a single subpopulation of cells with PGF2 alpha-R and that subpopulation is the interstitial or Leydig cell subpopulation. Cell and tissue types negative for immunoreactive PGF2 alpha-R include: the capsule (tunica albuginea) and subcapsular stroma, all histologic layers of the vasculature (both venules and arterioles), peritubular stroma, peritubular boundary tissue, spermatogonia, primary and secondary spermatocytes, spermatids, Sertoli cells, and spermatozoa. While the above described localization of PGF2 alpha-R is also seen in rat, there are fewer rat Leydig cells and this subpopulation appears to atrophy and stain less intensely with increasing age of the animal. Preabsorption of the PGF2 alpha-R antiserum with a corpora lutea homogenate acetone powder eliminated immunohistochemical staining of the Leydig cell subpopulation further suggesting that the antigenic determinant detected here is related to that in the ovary (PGF2 alpha-R). PMID- 1283466 TI - The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver. AB - In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect. PMID- 1283467 TI - Recent National Cancer Institute lymphoma trials of etoposide-containing combination chemotherapy. AB - Short-course prednisone/doxorubicin/cyclophospha- mide/etoposide cytarabine/bleomycin/vincristine/methotrexate (ProMACE-CytaBOM) contains the same drugs as standard ProMACE-CytaBOM but is delivered weekly for 16 weeks rather than 2 weeks out of 3 for 18 weeks. This results in a significant increase in dose intensity, ranging from 27% to 65% for all drugs. A total of 46 patients have been treated with short-course ProMACE-CytaBOM. The overall complete response rate of 91% and relapse rate of 17% compares favorably with results obtained using standard ProMACE-CytaBOM (86% and 27%, respectively). Toxicity was slightly greater with short-course therapy, but in general the regimen was well tolerated. Further dose intensification is possible in eligible patients by dose escalating myelotoxic drugs. A second strategy for augmenting the dose intensity is to deliver the drugs by continuous intravenous infusion. Infusional chemotherapy with doxorubicin/etoposide/vincristine/oral prednisone/bolus cyclophosphamide (EPOCH) results in significant antitumor activity in heavily pretreated patients with chemotherapy-resistant Hodgkin's disease and non Hodgkin's lymphomas. Complete responses or partial responses were seen in 91% of 21 evaluable patients. PMID- 1283468 TI - [Treatment of prostatic pathology with local hyperthermia. Analysis of the results of a study on 60 patients]. AB - The authors report the results of the hyperthermic treatment employed from January 1989 to April 1991 in 60 patients with BPH, PR and NP. Analysis of the results shows a determinant role for prostatitis (RC: 73.91%); the results for BPH are equally valid (RC: 56.25%). The authors used the same treatment for BPH with initially obstructive urinary symptomatology. PMID- 1283469 TI - [Sexually transmitted papillomavirus infections]. PMID- 1283470 TI - Phorbol ester induces down-regulation of CD4 molecule expression and resistance to in vitro infection by HIV1. AB - In vitro infectivity of the MT4 lymphoid cell line with human immunodeficiency virus (HIV) has been studied in correlation with the degree of expression of the CD4 molecule at the cell surface. To modulate this CD4 expression in vitro, pre incubation with phorbol myristate acetate (PMA) was used. The lowest CD4 expression was obtained after 1 to 5 hours. Thereafter, a partial re-expression of OKT4 was observed, e.g., when the incubation time with PMA was extended to 20 hours. Reverse transcriptase (RT) activity decreased and was delayed proportionally to the length of incubation of cells with PMA. This observation was confirmed by the comparable variation of cytopathic effects and of p24 antigen release in culture supernatants. The decrease in HIV infectivity hence correlated with that of OKT4 expression when PMA treatment did not exceed a few hours. By contrast, after extended treatment, infectivity remained decreased although OKT4 expression reappeared. PMID- 1283471 TI - [The regulatory role of pulmonary surfactant in macrophage metabolism]. AB - The surfactant was isolated from rat lung tissue and its effect on biosynthesis of DNA, RNA and protein as well as content of cyclic nucleotides and prostaglandins was studied in macrophages. When the surfactant was incubated simultaneously with lung macrophages within 6 hrs, an initial inhibition and subsequent activation of DNA, RNA and protein synthesis were observed. Stimulation of protein synthesis was found to follow the increase in the biosynthesis of DNA and RNA. At the same time, the surfactant induced elevation of cAMP in the macrophages within 1 hr of cultivation, while content of cGMP was decreased within 3 and 6 hrs. Content of prostaglandins E was increased in the cells and concentration of prostaglandin F2 alpha was decreased within 6 hrs. The findings suggest that the surfactant-mediated increase of DNA-induced protein synthesis was cAMP-, cGMP- and prostaglandin-dependent. PMID- 1283472 TI - Immunohistochemistry with keratin monoclonal antibodies in canine tissues: urogenital tract, respiratory tract, (neuro-)endocrine tissues, choroid plexus and spinal cord. AB - Twelve oligo- or monospecific monoclonal antibodies (MoAbs) directed against human keratin types were used in an immunohistochemical study of the canine male and female urogenital tract, the respiratory tract, the adrenal gland, the (para )thyroid gland, the choroid plexus and the spinal cord. The keratin MoAbs showed differences in staining patterns in the various epithelial tissues and the diverse epithelial cells. The kidney was characterized by a complex keratin staining pattern and the canine urothelium showed regional differences in keratin staining. Also in the female genital tract different keratin staining patterns were observed. Testicular and adrenal gland cells did not react with any of the keratin MoAbs. The keratin staining patterns in the various canine tissues showed, in addition to similarities, also distinct differences when compared to the staining patterns in corresponding tissues of other species, e.g. of man. These staining dissimilarities indicate that the reactivity patterns of the keratin MoAbs with restricted keratin immunoreactivity can not be always extrapolated from one species to another. Nevertheless, MoAbs directed against human keratin proteins can apparently be used to differentiate between various types of canine epithelia or epithelial compartments. PMID- 1283473 TI - [The content of DNA, RNA and protein and the fresh weight:DNA, protein:DNA and RNA:DNA ratios in tissue of male calves, bulls, short-scrotum bulls and oxen during the growth period]. AB - In male calves, in bulls, in short scrotum bulls and in oxen of different age the content of DNA, RNA and protein in various tissues (cerebrum, cerebellum, spinal cord, ventricles, lung, liver, cortex of the kidney, spleen, testicles, M. semimembranosus) was analysed. The fresh weight: DNA-, the protein: DNA- and the RNA: DNA-ratios were calculated. In the age of 78 weeks the short scrotum bulls had a body weight of 577 +/- 44, the bulls of 550 +/- 21 and the oxen of 462 +/- 41 kg. The testicles of the short scrotum bulls were smaller than that of the bulls. The differences in the content of DNA, RNA and protein per g tissue between male calves, bulls, short scrotum bulls and oxen of the same age were in part significant. The total content of DNA, of RNA and of protein for the 78 weeks old as well as the number of nuclei of the lung, the liver, the spleen and the testicles for the 6 and 78 weeks old animals were calculated. The biochemical parameters can be used for the characterization of the inhibition of growth of the different organs of calves and cattle by malnutrition and diseases. PMID- 1283474 TI - Topical retinoic acid treatment of photoaged skin: its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid. AB - Topical treatment with retinoic acid (tretinoin, vitamin A acid) has been reported to partly reverse signs of photodamage. To determine whether the histochemical distribution of hyaluronan (hyaluronic acid, HYA) in the epidermis and dermis and the amounts of HYA and retinoic acid in suction blister fluid were influenced by such topical treatment, 14 subjects healthy apart from moderate photodamage were instructed to treat the lateral forearm with 0.01-0.05% retinoic acid cream for 6 months. In a study of the short-term effects, another six subjects applied 0.05% retinoic acid cream for 2 weeks. After 6 months the thickness of the vital epidermis had increased by 23%. The HYA staining was based on a specific immunohistochemical method in which hyaluronan-binding protein is used. Before treatment HYA was seen as a meshwork around the cells in the upper half of the stratum spinosum. After 6 months of treatment this meshwork had increased in thickness by 31% compared with pretreatment specimens. The HYA staining was already intense in the papillary dermis before treatment and no difference was observed after 6 months' treatment. The mean concentration of HYA in blister fluid had increased significantly (43%) after 2 weeks of treatment whereas after 6 months there was no significant difference in this respect between the treated and untreated arm. The increase in the thickness of the epidermal HYA meshwork after 6 months and the blister fluid HYA after 2 weeks may indicate that HYA is involved in the epidermal change induced by topical retinoic acid therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283475 TI - Raynaud's phenomenon and intralesional bleomycin. PMID- 1283476 TI - Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism. AB - Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p < 0.05). GH peaks after GHRH+galanin were also significantly lower in hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p < 0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity. PMID- 1283477 TI - Defective stimulation of proliferation and collagen biosynthesis of human bone cells by serum from diabetic patients. AB - We studied the influence of fasting serum from nine insulin-dependent diabetic children and adolescents under insufficient metabolic control on normal human bone cells in vitro compared with serum from eight sex- and age-matched controls. Cell number 24 h after plating was significantly less under diabetic serum, indicating impaired cell attachment, spreading and initiation of cell proliferation. Cell number after five days was reduced by 1% diabetic serum, while higher serum concentrations had diverging effects on osteoblast proliferation. Collagen synthesis of human osteoblasts was significantly reduced by 8% diabetic serum compared to 8% control serum, while synthesis of non collagenous proteins was not affected. Duration of diabetes (several weeks up to 12 years) had no influence on these parameters. The serum from one patient, which was studied a second time under excellent metabolic control three months later, however, had lost its inhibitory influence on collagen synthesis of osteoblasts. The pattern of the interstitial collagen types I, III and V was not altered by diabetic serum. These results indicate that defective regulation of proliferation and collagen synthesis of osteoblasts by components present in human diabetic serum may be an important factor in the development of diabetic osteopenia. The negative influence might be explained in part by reduced levels of IGF-I and elevated levels of IGF binding protein-1 in the diabetic sera. PMID- 1283478 TI - Examination of antithyroid effects of smoking products in cultured thyroid follicles: only thiocyanate is a potent antithyroid agent. AB - We studied the antithyroid action of cigarette smoking products (nicotine, cotinine, and thiocyanate) in the physiological culture system of porcine thyroid follicles. Iodide uptake, iodine organification, de novo thyroid hormone formation, and iodide efflux were measured in the presence of 0-200 mumol/l nicotine, cotinine, or potassium thiocyanate. Nicotine and cotinine did not inhibit iodide transport or thyroid hormone formation. Thiocyanate concentrations equivalent to serum levels of smokers showed three independent antithyroid actions: (i) inhibition of iodide transport, (ii) inhibition of iodine organification, and (iii) increased iodide efflux. Inhibition of iodide transport by thiocyanate was competitive with iodide and independent of TSH concentration. Thiocyanate did not inhibit TSH mediated cAMP production or Na+K+ ATPase activity, a sodium pump for iodide transport. When 50 mumol/l thiocyanate was added 2 h after incubation with iodide or when 1 mumol/l thiocyanate was added from the beginning of incubation, iodine organification was inhibited without changing iodide transport. De novo thyroid hormone formation was clearly inhibited by 50 mumol/l thiocyanate. Thiocyanate increased iodide efflux although the degrees of iodide efflux by 10 mumol/l and 100 mumol/l thiocyanate did not differ significantly. In summary, thiocyanate, a product of smoking, has three independent antithyroid activities. The data of iodide transport kinetics suggest that thiocyanate can be an antithyroid agent particularly in iodine deficiency. PMID- 1283479 TI - Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells. AB - Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 micrograms/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 micrograms/l IGF-I and IGF-II) but increased the level of IGFBP-3 (3-10 fold at 100 micrograms/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4. PMID- 1283480 TI - [Platelet antigens]. AB - Platelet specific antigens and platelet antigens shared with other peripheral blood cells are presented. The molecular characteristics of membrane glycoproteins which are platelet specific determinants is discussed. PMID- 1283481 TI - Cytomegalovirus infection in children with blood diseases. AB - The study included 68 children aged from 1 to 16 years treated for acute leukemias and bone marrow aplasia. Cytomegalovirus antigen (CMV) was detected by immunofluorescence in urinary sediment cells and in cell cultures after their inoculation with CMV. Besides, the activity of IgG and IgM classes of antibodies against CMV was determined. Presence of one or more markers of CMV infection was demonstrated in 31 children, i.e., 45.5%. In eight children (11.7%) clinical manifestation of CMV infection were demonstrable with fever, hepatitis, pneumonia, rash. In all the children who completed the treatment with hyperimmune globulin, regression of clinical symptoms and signs of CMV infection with the elimination of virus antigen from urine was achieved. PMID- 1283482 TI - Marital discord and early child development. AB - As part of a prospective study on the neuropsychiatric development of children born at varying degrees of organic and psychosocial risk, the effect of marital discord on the cognitive and social-emotional development of 315 first-born children into two parent households was investigated. Both the children and the quality of the parental relationship were evaluated when the children were 3 months and 2 years of age. The findings show that marital discord at 3 months does not affect child performance at 3 months, or at 24 months. Marital discord at 2 years does affect the emotional well-being of the 2 year olds, i.e. it is accompanied by a significant rise in psychopathological symptoms. When the effect of the stability of marital strife from the first assessment to the second was studied, a significant increase of behaviour problems and decrease in cognitive performance was found in the group of children whose parents' marital situation had deteriorated and failed in the meantime but surprisingly not in the group with chronic discordant relationships. Conversely, poor child performance and emotional adjustment improved with a positive change in the parental relationships. Analysis shows that negative marital change goes hand in hand with a decrease in parenting skills which affect children more adversely than their counterparts whose parents had a history of marriage and child-rearing problems. Further study of the course of marital relationships and child development at the next research waves (4.5 and 8 years) will show which results are of long-term versus short-term relevance. PMID- 1283483 TI - NMDA-receptor blockers but not NBQX, an AMPA-receptor antagonist, inhibit spreading depression in the rat brain. AB - The effect of different glutamate-receptor antagonists on the induction of cortical spreading depression of Leao and of cortical anoxic membrane depolarization were investigated in the anaesthetized rat. Spreading depression (SD), elicited by mechanical stimulation of the cortical surface, was inhibited by the non-competitive N-methyl-D-aspartate (NMDA)-receptor blocker, (+-)-5 methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclo-hepten-5,10-imi ne maleate (dizocilpine or MK-801), (0.30 mumol kg-1 (0.10 mg kg-1)), and the competitive NMDA-receptor antagonists; cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755), (3.36 mumol kg-1 (0.75 mg kg-1)), D-(E)-2-amino-4-methyl-5-phosphono-3 pentenoic acid (CGP 40116), (1.20 mumol kg-1 (0.25 mg kg-1)) and its carboxylester CGP 43487, (6.30 mumol kg-1 (1.50 mg kg-1)). The alpha-amino-3 hydroxy-5-methyl-4-isoxazolepripriate (AMPA)-receptor blocker, 2,3-dihydroxy-6 nitro-7-sulfamoyl-benzo(F) quinoxaline (NBQX), administered as an intravenous dose of 29.76 and 89.29 mumol kg-1 (10 & 30 mg kg-1), which is sufficient to block seizures and protect against ischaemic brain damage, did not inhibit spreading depression. None of the drugs utilized inhibited the anoxic membrane depolarization. The data demonstrate that NMDA-receptor activation is essential for the initiation and propagation of spreading depression, while activation of AMPA-receptors is not obligatory. The observed initiation and propagation of SD, during AMPA-receptor blockade, suggest that activation of voltage-operated ion channels may contribute to release the magnesium block of the NMDA-receptor operated channel and to the initiation of SD. PMID- 1283484 TI - Relative involvement of substance P and CGRP mechanisms in antidromic vasodilation in the rat skin. PMID- 1283485 TI - Effects of nerve growth factor and acetyl-L-carnitine arginyl amide on the human neuronal line HCN-1A. AB - The HCN-1A clonal cell line, derived from the cortical tissue of a patient with unilateral megencephaly, was shown to differentiate into a mature neuronal-like state in the presence of the nerve growth factor, dibutyryl cyclic adenosine, 3',5'-monophosphate and either 1-isobutyl-3-methylxanthine or forskolin. Differentiation was assessed by measuring the percentage of cells that displayed branched, varicose processes that stained for synaptophysin. Treatment of cultures with a cocktail containing forskolin increased immunocytochemical staining for gamma aminobutyric (GABA), neurofilament protein and the nerve growth factor receptor species p75NGFR. Treatment with acetyl-L-carnitine alone had some effects on the cell morphology while acetyl-L-carnitine arginyl amide and nerve growth factor together increased the GABA content. Positive staining levels for the neurotransmitters gamma aminobutyric acid, glutamate, somatostatin, cholecystokinin and vasoactive intestinal polypeptide were measured quantitatively for HCN-1A under basal conditions. PMID- 1283486 TI - Microcephalic cerebrum with hypomyelination in the pygmy mouse (pg). AB - To determine whether somatomedin has a direct action on cerebral development instead of an indirect action of a growth hormone, we examined the central nervous system of the pygmy mouse (pg), a mutant with normal somatomedin activity. Our findings are: (A) the weights of the pg/pg cerebrum and cerebellum weighted were significantly less than those of the normal controls (pg/+), 14 and 15% less, respectively; (B) the total DNA content was reduced by 17% in the cerebrum and cerebellum of the pg/pg mouse; (C) the total RNA content was reduced in the cerebrum and cerebellum, proportional to the reduction in DNA; (D) CNPase activity was reduced selectively in the cerebrum of the pg/pg mouse by 25%; and (E) the pg/pg mice exhibited a strikingly reduced level of activity with an indistinct diurnal periodicity. Therefore, the present findings suggest that the action of somatomedin on the proliferation and maturation of glial cells might be a necessary precondition to myelin formation. PMID- 1283487 TI - Effect of hyperthermia on the antitumor actions of interferons. AB - Hyperthermia treatment has been shown to enhance the in vitro antiproliferative effects of IFN-alpha, IFN-beta, and IFN-gamma, with IFN-gamma being more strongly enhanced than IFN-alpha. The comparative effects of hyperthermia on the in vivo antitumor activities of IFN-alpha and IFN-gamma were evaluated in the murine system using both subcutaneous and intraperitoneal B16 melanoma tumor model systems. Heat-induced whole body hyperthermia, resulting in a 2 degree C rise in body temperature, was administered by incubating the mice for 8 hours in a dry incubator at 37.1 degrees C. Whole body hyperthermia was found to enhance the antitumor activity of IFN-alpha by approximately 1.0 fold and 1.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented an additive effect of hyperthermia and IFN-alpha. Hyperthermia was found to enhance the antitumor activity of IFN-gamma by approximately 2.9 fold and 2.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented a synergistic effect of hyperthermia and IFN-gamma. The results of this in vivo study confirm and extend the in vitro observation that hyperthermia more strongly enhances the antitumor action of IFN-gamma than IFN-alpha. These results may have clinical importance because they suggest that hyperthermia may be used in combination with IFN-gamma to provide a synergistically enhanced antitumor action. PMID- 1283488 TI - Determination of genome size of Haemophilus influenzae Sb: analysis of DNA restriction fragments. AB - Genomic DNA size was measured in clinical isolates of Haemophilus influenzae by Pulsed-Field Gel Electrophoresis of DNA restriction fragments. Because of the high (64%) A+T content of H. influenzae DNA, restriction enzymes that recognize sequences with at least four GC base pairs were expected to be rare cutters. Five enzymes that produced fragments greater than 200 kb in size were used to digest intact chromosomes and fragments resolved by TAFE and/or FIGE: ApaI (GGGCCC), EagI (CGGCCG), NotI (GCGGCCGC), RsrI (CGGA/TCCG), and SmaI (CCCGGG). All five had recognition sequences with at least six GC base pairs. The genomic DNA size of H. influenzae serotype b, estimated with ApaI, EagI, NotI, RsrII, and SmaI, is 1,950 kb. PMID- 1283489 TI - Staphylococcal lipase affects phagocytosis of Staphylococcus aureus by human granulocytes and monocytes. AB - The rate of immunological and non-immunological phagocytosis of staphylococci by lipase pre-treated human granulocytes and monocytes was compared. It was found that the effect of this enzyme on two types of cells is opposite. Lipase decreases phagocytosis by granulocytes and increases by monocytes. The revealed differences between phagocytosing cells studied prompted us to investigate the influence of lipase on Fc receptors on these cells (rosette EA test). The different susceptibility of Fc receptors on non-activated phagocytes to lipase was found. This could be at least partially responsible for the difference observed between phagocytic activity of granulocytes (decreased) and monocytes (increased) pretreated with staphylococcal lipase. Inactivated enzyme showed a similar effect as active enzyme in the case of granulocytes. However, inactivated enzyme had no effect on rosette formation by lipase pretreated monocytes, indicating an enzymatic effect. PMID- 1283490 TI - Transformation of Thiobacillus versutus with plasmid DNA. AB - The representative of the facultatively chemolithotrophic thiobacilli, Thiobacillus versutus has been successfully transformed for the first time with plasmid DNA. The plasmid used for the transformation study was pKK2, a derivative of the broad host range pSa plasmid conferring Km resistance being effectively expressed in T. versutus. Different methods inducing an artificial state of competence were tested. Transformants were obtained at the efficiency of about 10(3) per micrograms of DNA. pKK2 appeared to be compatible with T. versutus indigenous plasmids, but for stable maintenance it required constant selective pressure. PMID- 1283491 TI - A rapid agar-diffusion test for quantifying the toxic effects of copper on microorganisms. AB - The rapid agar diffusion test for quantifying the toxic effects of copper on microorganisms was elaborated. The assay was run in standard Petri dishes containing Czapek Solution Agar (Difco). Immediately after inoculation with the organism tested 3.2 mm diameter wells were punched in the agar. Wells were filled (20 microliters) with distilled water (control) and a range of solutions containing 128 to 4096 ppm Cu2+ (as CuSO4). After incubation (2-5 days, 26 degrees C) the diameters of Cu-inhibition zones were measured. Cu-sensitivity indices (ICu's) were calculated according to the formula: ICu = a2/(3.2-b), where: a--slope of the linear regression equation: log [Cu] (x)--inhibition zone diameter (y), b--intercept of the same equation. Additionally for characterization of Cu-sensitivity of the organism tested the predicted highest non-inhibitory Cu concentration (10c) was calculated, where: c = (3.2-b)/a. Both ICu's and adjusted average diameters of Cu-inhibition zones characterized well the Cu-sensitivity in organisms tested, as indicated by the statistical analyses. ICu's correlated very well (negative correlation) with 50% effective doses (Ed50's) of Cu2+ for mycelial growth of Cylindrocarpon destructans. The applicability of the elaborated assay in ecotoxicological studies was discussed. PMID- 1283492 TI - Effect of Penicillium expansum culture conditions on patulin production. AB - Penicillium expansum strains grown on Capek-Dox liquid medium excreted patulin to the medium. Its amount increased until day 12, then smaller amounts of the toxin were observed. Maximum patulin excretion took place at 25 degrees C, pH 6, although at 5 degrees C, pH 3 the presence of this mycotoxin was also observed. The highest amount of patulin produced was observed in medium containing fructose. PMID- 1283493 TI - Effect of preservatives on patulin production by Penicillium expansum. AB - Penicillium expansum has been grown on Capek-Dox medium using glucose and fructose as carbon source. Preservatives used in fruit processing and introduced in the medium were sorbic acid, formic acid, benzoic acid, SO2 and saccharose. Sulphur dioxide had a most inhibitory effect on mycelium growth and patulin production, formic acid concentration of 0.025% increased the amount of patulin by about 30% as compared to the culture with no preservatives. However its higher concentrations inhibited synthesis of this mycotoxin. Sorbic acid concentration of 0.1% stimulated the fungus strains examined in patulin synthesis but its highest amounts were detected using 0.0125% benzoic acid increased patulin secretion from 8 to 50% as compared to the control, depending on the strain examined. Saccharose concentration up to 50% clearly decreased patulin content in the medium until its total disappearance. PMID- 1283494 TI - Hormone refractory prostatic cancer: the role of radiolabelled diphosphonates and growth factor inhibitors. PMID- 1283495 TI - Localization of basic fibroblast growth factor (bFGF) in a metastatic cell line (AT-3) established from the Dunning prostatic carcinoma of rat: application of a specific monoclonal antibody. AB - Localization of basic fibroblast growth factor (bFGF) in a metastatic cell line, AT-3, established from the Dunning prostatic carcinoma of rat was determined by two immunological techniques using a specific monoclonal antibody against bFGF. Concentration of bFGF in cell extract was measured by sandwich radioimmunoassay (RIA) with heparin-Sepharose and 125I-labeled monoclonal antibody. bFGF concentration in the extract of AT-3 cells increased with increasing concentration of NaCl in extraction buffer. Localization of bFGF in AT-3 cells was determined by counting radioactivity of 125I-labeled monoclonal antibody binding to AT-3 cells before or after increasing permeability of the cells. The binding increased significantly by this treatment, indicating that bFGF within the cells was detected. PMID- 1283496 TI - Use of a reconstituted basement membrane to study the invasiveness of tumor cells. AB - We have used an extract of basement membranes which can be reconstituted into a biologically active gel matrix composed predominantly of collagen IV, laminin, nidogen, and heparin sulfate proteoglycan, in order to study the mechanisms involved in tumor cell invasion. When layered onto a porous filter in a Boyden chamber, the gel forms a barrier to the passage of normal cells. Malignant cells are able to cross this layer when the conditioned medium of NIH 3T3 cells is used as a chemoattractant to stimulate cell migration. A variety of human tumor cells have thus been studied in this system and we find a high correlation between their invasiveness in vitro and their malignant behavior as exhibited in vivo. We have used this in vitro invasion assay to test for factors which might inhibit tumor cell invasion. Collagenase IV is produced by malignant cells and is thought to be required for invasion. Indeed, inhibitors of this enzyme have demonstrated reduced tumor cell invasiveness. One site of five amino acids, on the B1 chain, which has been shown to promote cell adhesion, migration and binding to laminin receptor, was found to inhibit the invasion of tumor cells. In addition, factors which elevated cAMP levels were also able to suppress the invasiveness of tumor cells. These data suggest that the assay system described herein can be successfully utilized to study the invasive activity of tumor cells and those factors that may inhibit the spread of malignant cells. PMID- 1283497 TI - Studies on the pathogenesis of osteoblastic metastases by prostate cancer. PMID- 1283498 TI - Nucleolar organizer regions in prostate cancer. AB - A silver colloid technique for the staining of nucleolar organizer regions (NORs) was applied to paraffin sections of 52 clinical prostate cancers, 5 incidental carcinomas of the prostate, 12 benign prostatic hypertrophy (BPH) specimens and 7 normal prostates. The mean numbers of silver-stained NORs (AgNORs) in these lesions were 3.12 +/- 0.52 in clinical cancer, 2.65 +/- 0.64 in incidental cancer, 1.66 +/- 0.16 in BPH, and 1.76 +/- 0.22 in normal prostate. There was a statistically significant difference in agNORs numbers between cancer and benign prostatic tissues (p < 0.001). However, no significant difference was observed in AgNORs numbers between incidental and clinical carcinoma of the prostate. In clinical cancer, only poorly differentiated adenocarcinoma showed a statistically larger number of AgNORs than the well or moderately differentiated group (p < 0.02). Correlation between AgNORs numbers and clinical stage was not obvious. There was no relationship between the number of AgNORs and serum values of tumor markers such as PAP, PSA and gamma-Sm. Moreover, the AgNORs numbers did not show a relation to decreasing rates of serum marker levels during successful anti androgen therapy. If the patients with prostate cancer were divided into two groups by 2.9 of AgNORs number, the group with the smaller number of AgNORs (n = 14) was found to have a tendency towards a longer disease-stabilizing period than the larger group (n = 17). PMID- 1283499 TI - Computed tomographic evaluation of bone metastases in prostatic cancer patients. AB - This report provides new morphological insights, based on diagnostic methods, into metastases to the bone in prostate cancer patients. Lumbar CT examination is available to evaluate whether metastases are truly present or not, especially in aged patients with positive bone scans. The evaluation of response is clearer on CT. Furthermore, CT is useful not only in estimating the presence of metastases, CT also provides definite details on the extent of the metastatic condition. PMID- 1283500 TI - Radiation treatment of prostate bone metastases and the biological considerations. AB - This contribution on the biology and management of bone metastases from prostatic cancer is divided into three parts. The first details a study conducted at Stanford University on the prevention of bone metastases in the lumbar spine, in patients in whom the lumbar spine has been irradiated coincidental to the radiation treatment of the paraaortic lymph nodes. The incidence of metastases was significantly reduced in 71 patients in whom the apparently normal lumbar spine was irradiated, as compared to the incidence of metastases in 65 patients who received no lumbar irradiation. The implications of these observations on developing strategies for early, or preemptive, irradiation for bone metastases are discussed. In the second part, the optimum radiation dose and fractionation scheme for the palliation of overt bone metastases is addressed. Drawing largely from the work of Arcangeli et al., a total dose of 40-50 Gy*, fractionated at 2 Gy per day, seems to be the regimen of choice for enduring pain relief for most patients with prostatic metastases to bone. Finally, the recent utilization of strontium-89 in the palliation of advanced bone metastases is addressed. *The Gy is the current international unit of radiation. 1Gy = 100 Rad; 1cGy (centigray) = 1 Rad. PMID- 1283501 TI - Clinical course of bone metastasis from prostatic cancer following endocrine therapy: examination with bone x-ray. AB - X-ray findings of bone metastatic lesions from 81 cases of stage D2 prostatic cancer were examined before and following endocrine therapy. Untreated lesions were classified into five types; osteoblastic (15%), mixed, but mainly osteoblastic (31%), mixed, but mainly osteolytic (17%), osteolytic (10%), and undetermined with a positive bone scan (27%). Patients with two mixed types had a tendency of widely speeded areas of metastasis and elevated serum prostatic acid phosphatase. Temporal enlargement of sclerotic lesion immediately after the start of therapy did not indicate disease progression. In many cases, changes from osteolytic to osteoblastic patterns were noticed in the same lesion regardless of the effects of endocrine therapy. Remodeling to the sclerotic pattern appeared as curative changes. From these findings, it was concluded that the natural course of bone lesions showed a tendency to change from the osteolytic to osteoblastic type and relapse was often accompanied by an increase of the osteolytic type lesion. Evaluation of therapeutic effects based on remodeling, changes in number and areas of lesions, and the appearance of new lesion correlated well with prognosis. PMID- 1283502 TI - Palliative radiotherapy of bone metastasis. AB - We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months. PMID- 1283503 TI - Comparative study of prostatic carcinoma bone metastasis among Japanese in Japan and Japanese Americans and whites in Hawaii. AB - Metastatic prostate carcinomas in autopsy cases from three populations 49 cases of indigenous Japanese, 29 cases of Japanese Americans and 14 from whites in Hawaii) were compared in terms of their clinicopathological, immunohistochemical (tenascin and ras p21) and lectin binding (Helix Pomatia antigen, HPA) properties. Only the clinicopathological features were analyzed in the cases of whites in Hawaii. The results indicate that poorly differentiated carcinoma is less common, whereas distant metastasis is more frequent, in indigenous Japanese. Some of the Japanese-American cases with poorly differentiated carcinomas did not show any distant metastases. HPA and ras p21 expression are more common, but tenascin is less common in indigenous Japanese. HPA expression is more common in cases with metastasis, especially with metastasis to the bone and other organs, than nonmetastatic cases. Prostatic cancer cases in indigenous Japanese were more aggressive biologically than those in Japanese Americans, but no phenotypic differences were seen relevant to the presence or absence of bone metastases. PMID- 1283505 TI - The concentrations of GABA, 5-HIAA and HVA in the cerebrospinal fluid of children with infantile spasms and the effects of ACTH treatment. AB - Children with infantile spasms (IS) are generally treated with ACTH although little is known of the biochemical basis of the symptoms and the mechanism of this therapy. We have measured the concentrations of gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of IS children, followed the effect of ACTH treatment on these parameters and correlated CSF GABA values with the cause of IS, cranial CT findings and antiepileptic treatment. While significant differences in GABA concentrations were found between the children with IS and those with febrile seizures or nonconvulsive symptoms, these could be accounted for by age, not the disease present. The CSF GABA level was highest in the IS children with normal CT, cryptogenic cause and no antiepileptic treatment, and lowest in those with abnormal CT, symptomatic cause and antiepileptic treatment. The basal level of CSF 5-HIAA in the IS children was higher than that in the nonconvulsive children, but HVA levels did not differ. ACTH therapy did not change the CSF levels of GABA, 5-HIAA and HVA significantly. PMID- 1283504 TI - [Value of PSA in the staging of prostatic cancer]. AB - The clinical value of Serum Prostate Specific Antigen (PSA) in the staging of prostatic carcinoma was evaluated in 62 patients who underwent radical retropubic prostatectomy. Preoperative levels of PSA were compared with the final pathological stage obtained from all surgical specimens examined for capsular penetration, seminal vesical invasion and lymph node involvement. PSA level was closely correlated with the volume and the stage of the prostatic carcinoma. 93% of the patients with PSA < or = 10 ng/ml had tumor confined to the gland. All patients with PSA > 20 ng/ml had extraprostatic tumor extension (stage C or D). Patients with histologically proved prostatic carcinoma, PSA > 20 ng/ml and negative bone scan can be assumed to have extraprostatic disease and/or lymphatic involvement. Patients with PSA (drawn in the requested conditions) < or = 10 ng/ml can be considered to have organ confined disease, and can be spared a bone scintigraphy. Our study indicate an increasing role of PSA in the clinical staging of patients with prostatic carcinoma. PMID- 1283506 TI - Neuroleptic malignant syndrome-like state in a patient with Down syndrome and basal ganglia calcification. AB - We report a case of rhabdomyolysis in a 13-year-old Down syndrome patient with progressive quadriplegia, choreoathetosis and dystonia. Cranial CT demonstrated bilateral basal ganglia calcification. He experienced the sudden onset of high fever, cloudiness of consciousness, muscle rigidity and severe opisthotonus. The diagnosis was made on the basis of the marked increases in serum creatine kinase and myoglobin. There was remarkable elevation of 5-hydroxyindoleacetic acid, homovanillic acid and methoxy-hydroxyphenyl glycol in the cerebrospinal fluid during hyperpyrexia. This case exhibited almost all the diagnostic criteria of the neuroleptic malignant syndrome. It was suggested that abnormalities of monoamines in the central nervous system may be related to the pathologic etiology of this state and rhabdomyolysis. PMID- 1283507 TI - Significant factors in the disinfection and sterilization of flexible endoscopes. AB - BACKGROUND: Many nosocomial infection outbreaks have been linked to improper disinfection of the flexible endoscopes used in hospitals and clinics. The objective of this study was to evaluate the efficacy of scope disinfection with glutaraldehyde and hydrogen peroxide in manual and mechanical protocols. METHODS: Bacillus subtilis and Pseudomonas cepacia were the test organisms. Each channel in two different endoscopes was seeded and evaluated separately. Residual chemical germicide levels in the channels and in the work environment were also measured. RESULTS: Parametric analyses were carried out on log transformations of number of colony-forming units recovered. Repeated measures analysis demonstrated that both the type of disinfectant and the method of washing were significant factors for disinfection. CONCLUSIONS: Hydrogen peroxide proved to be more efficacious than glutaraldehyde for killing or removing B. subtilis in a 10 minute contact period. Automatic disinfection was more efficacious than manual disinfection for killing or removing B. subtilis in a 10-minute contact period. The channel being disinfected also proved to be a significant factor, with carbon dioxide and elevator channels the most difficult to disinfect consistently. PMID- 1283508 TI - A BamHI polymorphism in ovine wool cuticle keratin sequences. PMID- 1283509 TI - MspI and SstI RFLPs at the porcine prolactin locus (PRL). PMID- 1283510 TI - [Classical conditioning of anaphylaxis in sensitized guinea pigs]. AB - An attempt of classical conditioning of anaphylaxis by odor was carried out, using actively sensitized guinea pigs with an inhalation of ovalbumin (OA). One month after sensitization, animals were divided into the conditioned group; group C, and the unconditioned group; group U, consisted of 6 animals, respectively. Dimethylsulfied (DMS: sulfur odor), was inhaled in group C as a conditioned stimulus with OA which is an unconditioned stimulus, while only OA was inhaled in group U. Four days after these procedures, saline was inhaled in group C and DMS was solely inhaled in group U in order to equalize the total inhaled dose of OA and DMS in both groups. These sessions were repeated once a week for seven weeks. After final sessions, all animals were inhaled DMS, saline and OA separately, and blood samples were drawn after each inhalation to measure plasma histamine levels. After an inhalation of DMS only, plasma histamine levels of group C and U were 47.5 +/- 9.7 and 25.7 +/- 1.2 ng/ml, respectively. In group C, plasma histamine levels were 32.9 +/- 4.7 at the inhalation of saline and 59.0 +/- 9.2 ng/ml at OA inhalation. Plasma histamine level after an inhalation of DMS only was significantly higher in group C than that in group U (p < 0.05). These results suggest that the conditional stimulus (DMS inhalation) may induce histamine release in the absence of any antigenic stimulus and support the evidence for mast cell-neuron interaction. PMID- 1283511 TI - Heterophile antigens in serous cystadenocarcinoma of the human ovary. AB - As the aberrance of carbohydrate moieties, the appearance of heterophile antigens in human ovarian cancer tissue was studied using various heterophile antigens and antibodies together with antisera raised in rabbits by immunization with extracts of human ovarian cancer tissues. In the immunodiffusion test, rabbit antisera reacted with a heat-stable, perchloric-acid extractable antigen that was different from CEA and CA125 and possessed Hanganutziu-Deicher (HD)-type specificity in all 4 specimens of serous cystadenocarcinoma of the ovary. Furthermore, a pathologic serum with strong HD-antibody complex formed a precipitin line with one of them. In the cancer tissue, we also immunochemically demonstrated the presence of rat-erythrocyte antigens. However, other types of heterophile antigens, such as Paul-Bunnell and Forssman, were not detected. These results suggest that HD-type antigens appear in serous cystadenocarcinoma of the human ovary, one in broad distribution and some in specific cases. PMID- 1283512 TI - Rapid axonal transport velocity is reduced in experimental ethylene oxide neuropathy. AB - Chronic exposure of rats to ethylene oxide (EO) causes distal axonal neuropathy of lumbosacral primary sensory neurons. To study the pathogenesis of this neuropathy, we measured rapid axonal transport in peripheral nerves. Rats were exposed for 6 h to 500 ppm EO in a chamber three times a wk for 15 wk. Rapid axonal transport and quantitative histological alterations of peripheral nerves were studied. After [35S]methionine injection into the dorsal root ganglion, the velocity of rapid anterograde axonal transport of radioisotope-labeled protein was measured. The velocity in the rats exposed to EO was 33% less than that in control rats exposed to filtered room air. However, histological differences were slight. Morphometric studies showed that in EO-exposed rats, only the distal portions of the sural nerve had significantly greater incidental degeneration of myelinated fibers than did controls. There were significantly fewer large myelinated fibers only in the distals peroneal nerve. Therefore, a decrease in the velocity of anterograde axonal transport, related to these slight histological abnormalities of the peripheral nerve, may play a causative role in the development of the distal axonal neuropathy owing to chronic EO exposure. PMID- 1283513 TI - [Intralesional therapy with natural interferon-beta in refractory squamous epithelial cancers of the ENT area]. AB - It has been the aim of the present investigation to study the effect of intratumorally applied human fibroblast interferon (nIFN-beta; Fiblaferon 5 for the first two weeks, and Fiblaferon 3 three times a week) in a phase-II clinical trial of thirteen patients with advanced head and neck squamous cell carcinomas. All of the patients had failed established therapeutic modalities before and could not be treated by conventional procedures. nIFN-beta was injected intratumorally and its effect on tumour size was assessed by an independent, second observer as well as via CT and MR imaging. All assessments were done prior to treatment, 8 weeks after beginning treatment and at 16 weeks. Three female and ten male patients with primary tumours of the hypopharynx (n = 5), the larynx (n = 4), the oropharynx (n = 1), the glandula submandibularis (n = 1), the oral cavity (n = 1) and the oesophagus (n = 1) have undergone outpatient treatment three times a week. Tumour size showed no change in six patients while progressive disease occurred in seven cases after eight weeks of treatment. Radiological findings did not change in the nine patients continuing treatment while five showed progressive disease. There were no serious local or systemic side effects due to the intratumoral nIFN-beta treatment. The survival time was 9.73 months after the onset of nIFN-beta treatment. PMID- 1283514 TI - Rifamycins as inhibitors of retroviral reverse transcriptase from M-MuLV, RAV-2, and HIV-1. AB - 29 Rifamycins were tested for inhibition of Reverse Transcriptase (RT) as potential anti HIV drugs. Two purified commercial enzymes from M-MuLV and RAV-2 were used. Anti-RT activity was also measured on a crude lysate of HIV-1. The results show that some derivatives have interesting levels of activity on isolated M-MuLV and RAV-2 RTs, while they are less active on the RT in the crude HIV-1 lysate. The active derivatives include oximes and hydrazones, alkylaminoderivatives, open ansa-chain derivatives and derivatives carrying a modified nucleoside. PMID- 1283515 TI - Conformational analysis of receptor selective tachykinin analogs: senktide and septide. AB - The conformational behavior in solution of two receptor selective tachykinin agonists, senktide (succinyl-D-F-MeF-G-L-M-NH2) and septide (pQ-F-F-P-L-M-NH2) is described. Two dimensional cross relaxation NMR spectroscopy is used together with coupling constant data to obtain interproton distance constraints. These results are used in conjunction with semi-empirical energy computations to indicate favorable conformations. Senktide is found to have a high degree of conformational order which is attributed to rotational restriction associated with the N-methylation of phenylalanine. The lowest energy conformation in accord with the experimental interproton distances contains a beta-turn. Interproton distances indicate that septide exists as a random coil or in an extended chain conformation. Energy computations suggest that septide is primarily an extended chain with internal reorientation restricted by the proline residue. These results may be related to the selectivity of these peptides for different receptors, in that the analogs, with conformations more stable than tachykinins, are more receptor selective. PMID- 1283516 TI - An algebraic representation of RNA secondary structures. AB - This paper develops mathematical methods for describing and analyzing RNA secondary structures. It was motivated by the need to develop rigorous yet efficient methods to treat transitions from one secondary structure to another, which we propose here may occur as motions of loops within RNAs having appropriate sequences. In this approach a molecular sequence is described as a vector of the appropriate length. The concept of symmetries between nucleic acid sequences is developed, and the 48 possible different types of symmetries are described. Each secondary structure possible for a particular nucleotide sequence determines a symmetric, signed permutation matrix. The collection of all possible secondary structures is comprised of all matrices of this type whose left multiplication with the sequence vector leaves that vector unchanged. A transition between two secondary structures is given by the product of the two corresponding structure matrices. This formalism provides an efficient method for describing nucleic acid sequences that allows questions relating to secondary structures and transitions to be addressed using the powerful methods of abstract algebra. In particular, it facilitates the determination of possible secondary structures, including those containing pseudoknots. Although this paper concentrates on RNA structure, this formalism also can be applied to DNA. PMID- 1283517 TI - FTIR study of specific binding interactions between DNA minor groove binding ligands and polynucleotides. AB - The use of FTIR spectroscopy is made to study the interactions between polynucleotides and two series of minor groove binding compounds. The latter were developed and described previously as part of an ongoing program of rational design of modified ligands based on naturally occurring pyrrole amidine antibiotic netropsin, and varying the structure of bisbenzimidazole chromosomal stain Hoechst 33258. Characteristic IR absorptions due to the vibrations of thymidine and cytosine keto groups in polynucleotides containing AT and GC base pairs respectively are used to monitor their interaction with the added ligands. Although the two thiazole based lexitropsins based on netropsin structure differ in the relative orientation of nitrogen and sulfur atoms with respect to the concave edge of the molecules, they interact exclusively with the thymidine C2 = O carbonyl groups in the minor groove of the alternating AT polymer as evidenced by specific changes in the IR spectra. In the second series of compounds based on Hoechst 33258, the structure obtained by replacing the two benzimidazoles in the parent compound by a combination of pyridoimidazole and benzoxazole, exhibits changes in the carbonyl frequency region of poly dG.poly dC which is attributed to the ligand interaction at the minor groove of GC base pairs. In contrast, Hoechst 33258 itself interacts only with poly dA.poly dT. Weak or no interaction exists between the ligands and any of the polynucleotides at the levels of the phosphate groups or the deoxyribose units. PMID- 1283518 TI - Mapping of two new human B-cell epitopes on HIV-1 gp120. AB - OBJECTIVE: To map epitopes on gp120 defined by human antibodies and to examine the neutralizing activity of these antibodies. DESIGN AND METHODS: Serum from HIV 1-antibody-positive individuals was used to screen a random fragment expression library representing gp120 from the HIVIIIB clone BH10. The library was based on the pUEX1 expression vector. Serum was tested for in vitro neutralizing activity using H9 cells and the HIVIIIB isolate. RESULTS: Four different epitopes defined by human antibodies were mapped on gp120. Two of these have not previously been reported and are located within amino acids (aa) 90-100 in the C1 region and aa 355-365 in the semi-conserved region between V3 and V4. The other two are located within aa 140-145 and aa 286-309. These epitopes are situated in regions that have been shown to demarcate human epitopes. Three serum samples with neutralization titres > or = 1024 were identified. None of the purified antibody fractions defining the mapped epitopes on gp120 had any neutralizing capacity against HIVIIIB. CONCLUSIONS: This study is the first demonstration of the applicability of random fragment expression libraries for the direct screening of human serum in order to map epitopes on gp120. Two new epitopes and two previously identified epitopes were mapped in this way. However, none of the linear epitopes was defined by antibody fractions neutralizing HIVIIIB, and it was not possible to map epitopes defined by neutralizing antibodies in the serum samples capable of neutralizing HIVIIIB infection of H9 cells. Thus, it appears that the neutralizing activity of serum in this study was not due to anti-gp120 antibodies defining linear epitopes. PMID- 1283519 TI - The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study. AB - OBJECTIVE: To determine the safety and pharmacokinetics of the nucleoside analogue, 3TC. DESIGN: A Phase I, open-label, single-centre study. METHODS: Twenty asymptomatic, HIV-infected male patients with CD4 lymphocyte counts < 500 x 10(6)/l who had not received previous antiretroviral therapy completed the study. Each patient received a single intravenous dose followed by a single oral dose of 3TC. Four patients were dosed at each of five dose levels (0.25, 1.0, 2.0, 4.0 and 8.0 mg/kg). RESULTS: The most commonly reported adverse event was headache, which was generally reported to be mild. The mean bioavailability of 3TC was 82% following oral administration. The majority of the dose (approximately 70%) was excreted unchanged in the urine. CONCLUSIONS: Overall, 3TC was well tolerated following dosing, and there were no significant changes in the safety parameters measured. Phase I/II clinical trials with 3TC are ongoing to evaluate its safety, pharmacokinetics and preliminary activity. PMID- 1283520 TI - Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma. AB - OBJECTIVE: To determine the maximum tolerated dose of granulocyte-macrophage colony-stimulating factor (GM-CSF) that would reduce the severity and duration of neutropenia from combination cytotoxic chemotherapy in the treatment of AIDS related Kaposi's sarcoma (KS). DESIGN: Phase I, dose escalation. SETTING: Outpatient clinic of a university hospital. PATIENTS: HIV-seropositive patients with advanced KS. INTERVENTIONS: Combination chemotherapy consisting of adriamycin, bleomycin, and vincristine (ABV), with escalating doses of recombinant human GM-CSF (rhGM-CSF). Patients were treated for a median of six cycles (range, between two and seven cycles) of biweekly chemotherapy with GM-CSF administered in divided daily subcutaneous doses on days 2-12. Serum cytokine levels of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured before, during, and after therapy to correlate with response to therapy. RESULTS: A GM-CSF dose of 250 micrograms/m2 was well tolerated, whereas the next dose escalation, of 500 micrograms/m2, was associated with dose-limiting toxicities, including grade 3 fever, fatigue, and diarrhea. GM-CSF produced predictable cyclic increases in granulocytes, allowing for delivery of full-dose chemotherapy on schedule. All patients were HIV-p24-antigen-negative at study entry; no activation of p24 antigenemia was observed after repeat testing. Consistent changes in cytokine levels were not observed. Responses included one complete and three partial responses, and two patients with stable disease parameters. CONCLUSIONS: We conclude that GM-CSF can be administered safely to patients with AIDS-related KS receiving myelosuppressive chemotherapy, resulting in granulocytic response, without up-regulation of HIV p24 antigen levels in serum. PMID- 1283521 TI - AIDS-associated mucocutaneous Kaposi's sarcoma treated with bleomycin. AB - OBJECTIVES: To evaluate efficacy and tolerance of bleomycin in AIDS-associated mucocutaneous Kaposi's sarcoma. A previous study showed that bleomycin was effective and well tolerated in this setting. DESIGN: A non-comparative, open, prospective study. METHODS: Seventy patients were treated with 5 mg per day intramuscular bleomycin on 3 consecutive days every 2 weeks. RESULTS: Two patients achieved a complete response and 50 a partial response (overall response rate, 74%). Median time to treatment response was 4 weeks (range, 2-12 weeks) and median time to relapse 10 weeks (range, 2-36 weeks). Dose-limiting toxicity consisted of cutaneous adverse reactions. CONCLUSION: Bleomycin is active against AIDS-associated mucocutaneous Kaposi's sarcoma; relapse occurs after discontinuation of therapy. PMID- 1283522 TI - Identification of cross-reactive epitopes recognized by HIV-1 false-positive sera. PMID- 1283523 TI - [Pharmaceutical biotechnology]. PMID- 1283524 TI - Isolation of a gramicidin S hyperproducing strain of Bacillus brevis by use of a fluorescence activated cell sorting system. AB - A gramicidin S (GS) hyperproducing mutant of Bacillus brevis was isolated by using a protein-staining fluorescence dye (fluorescein isothiocyanate, FITC), and a fluorescence-activated cell sorting system (FACS). By flow cytometry (FCM) analysis after staining with FITC, higher producing cells of the wild-type had higher fluorescence signals than cells with low productivity or cells from a GS non-producing mutant. Staining with FITC did not affect the viability of cells under the conditions chosen for FCM analysis. This enabled us to recover viable cells after sorting. After wild-type cells were mutagenized with N-methyl-N' nitro-N-nitrosoguanidine, mutants with higher fluorescence than the parental strain were obtained by cell sorting. Among them, strain 18 was chosen as a GS hyperproducer; it produced 590 micrograms GS/ml compared to 350 micrograms/ml by the wild-type strain. This method has the advantage of being able to screen large numbers of cells in a short time. Furthermore, use of the fluorescence dye technique will expand the use of FACS to the improvement of other cultures that produce metabolites that do not have a specific fluorescence or strong enough fluorescence for normal cell sorting. PMID- 1283525 TI - Rapid assessment of bacterial viability by flow cytometry. AB - The ability of a flow cytometer to rapidly assess microbial viability was investigated using three vital stains: rhodamine 123 (Rh123); 3,3' dihexyloxacarbocyanine iodide [DiOC6(3)] and fluorescein diacetate (FDA). Rh123 was found to clearly differentiate viable from non-viable bacteria. The methodology for staining bacteria with this dye was optimised. Rh123 was shown to stain and discriminate several different species of viable bacteria although this was not universal. Viable cells of Bacillus subtilis were found to stain better with FDA than with Rh123. The results demonstrate the ability of flow cytometry to rapidly detect and estimate the viability of bacterial populations. PMID- 1283526 TI - Antibody epitopes sensitive to the state of human immunodeficiency virus type 1 gp41 oligomerization map to a putative alpha-helical region. AB - Two antibodies, affinity-purified from human immunodeficiency virus-positive human plasma with synthetic peptides in the region gp41(566-596), were found to recognize oligomeric gp41 more strongly than the monomeric form in an immunoblot assay. In contrast, a murine anti-gp160 monoclonal antibody, which maps within this sequence to gp41(581-596), recognized only monomeric gp41 after disruption of the oligomer with sodium dodecyl sulfate. This monoclonal anti-gp160 antibody did not recognize chemically crosslinked oligomeric gp41 that had been treated with similar conditions used to disrupt the gp41 oligomer. These results indicate that this epitope is inaccessible to binding by this antibody when gp41 is oligomeric. Cyanogen bromide cleavage of gp41 resulted in a 17-kD fragment Thr 541-Met-631. A significant proportion of this fragment was oligomeric when derived from chemically crosslinked gp41. The region Ala-566-Gln-596, within the cyanogen bromide fragment, contains the oligomerization-sensitive epitopes as well as two lysine residues available for crosslinkage. This region is relatively conserved and has the propensity to form an amphipathic alpha-helix. PMID- 1283527 TI - Early changes of urinary amylase isoenzymes in diabetes mellitus. AB - The altered excretion of isoenzymes of amylase in urine was used as an early indicator of the loss of electric charges in the glomerular basement membrane, in 202 juvenile-onset insulin-dependent diabetic patients, compared with the pattern of excretion in 51 normal subjects matched for age and sex. Diabetics showed an increased excretion of salivary amylase. The salivary to pancreatic amylase ratio in urine (S/P ratio) was always below 1 in control subjects, but was elevated in 33.2% of diabetics, although microalbuminuria was present in only 26.2% of diabetic patients. The concentrations of other proteins in urine were within the reference ranges in nearly all patients, indicating that the kidney was not seriously affected. The increased salivary amylase excretion was not due to changes in the plasma concentration of any of the isoamylases, but to a real increase in excretion, as its fractional excretion in relation to creatinine clearance was clearly increased (1.0 +/- 0.7 vs. 1.52 +/- 1.99, p < 0.05), and the ratio of their clearances was also increased (0.35 +/- 0.18 vs. 0.49 +/- 0.61, p > 0.05). Moreover, the prevalence of altered S/P ratios was higher than the prevalence of microalbuminuria (36.6% vs. 18.8% of patients in the first decade of evolution of insulin-dependent diabetes mellitus). Altered S/P ratios were most prevalent in the first decade, whereas microalbuminuria was most prevalent in the second decade of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283528 TI - Alpha 1-microglobulin (protein HC): features of a promising indicator of proximal tubular dysfunction. AB - alpha 1-Microglobulin (protein HC) is a stable urinary indicator protein which reflects acute and chronic dysfunctions of the proximal renal tubule. High urinary concentrations were found to be indicative of tubular drug toxicity, interstitial nephritis or chronic renal failure. The protein is synthesized by liver cells and readily associates with serum immunoglobulin A. Only the free form is filtered through the glomerulus and is reabsorbed by proximal tubular cells. The exact physiological function of this member of the new superfamily of lipocalins is still unknown, but there are indications that alpha 1-microglobulin (protein HC) may serve as an excretion vehicle for fluorescent, charge heterogeneous substances of unknown nature. Additionally, it seems to be associated with the humoral and cellular immune response. PMID- 1283529 TI - Masking the cryptodeterminant on the 54-kilodalton mouse sperm surface antigen. AB - Previously, we reported that the epitope of a 54-kDa sperm surface sialoglycoprotein on the flagellum is masked by sialic acid residues. The epitope is referred to as a hidden determinant or cryptodeterminant. This paper reports the manner in which the epitope is masked as evaluated qualitatively and quantitatively by means of SDS-PAGE/immunoblots (Western blot) and ELISA. Immunoblotting with four specific monoclonal antibodies to the 54-kDa sialoglycoprotein--T21 (IgM), MC71 (IgG1), MC81 (IgM), and MC91 (IgM)- demonstrated that not only IgM but also IgG antibody MC71 and the Fab fragment MC71 are masked. Quantitative evaluation with ELISA to compare the antibody titration curves of the masked and unmasked antigens on sialidase-treated and untreated sperm, respectively, indicated that sialidase caused the antibody binding ability of the epitopes to increase to a different level for each antibody. There were 32-256-, 8-16-, 16-, and 2-4-fold increases in binding to T21, MC71, MC81, and MC91 antibodies, respectively. These results suggest that the antigen-masking through the cryptodeterminant does not depend upon the subtype or the molecular mass of the antibody, but upon the biochemical nature of the epitope region that is closely related to the sialic acid. The mechanism and physiological roles of the antigen-masking are discussed. PMID- 1283530 TI - Distribution of beta 1 integrin subunit in rat seminiferous epithelium. AB - We have studied the presence and distribution of beta 1 integrins in the seminiferous epithelium of prepubertal and adult rats. Our immunofluorescence data show that in the adult the antibody recognizes specific areas localized around the heads of elongating and maturing spermatids and above spermatogonia at stages I-VII. The following were found to be negative: a) areas adjacent to spermatogonia at stages IX-XIV and adjacent to spermatocytes and to round spermatids; b) spermiated spermatozoa. In the prepubertal rat, positive tubules are first apparent around Day 17 of age. Immunofluorescence and immunoprecipitation studies show that Sertoli cell monolayers from 3-wk-old rats express beta integrins in vitro. PMID- 1283531 TI - Polyclonal antibodies against the rat NK1 receptor: characterization and localization in the spinal cord. AB - We have developed antibodies against the NK1 receptor and have investigated its cellular distribution. Rabbit polyclonal antibodies were generated against peptide (19-32) of the rat brain NK1 receptor. They were very specific to the NK1 site as shown by ELISA against various epitopes of NK1, NK2 and NK3 receptors and by immunoblotting of proteins from bacteria transfected with rat brain NK1 receptor cDNA and from rat cortex. Determining how immunostained NK1 receptors are distributed in the rat spinal cord made it possible to identify the cellular structures on which NK1 receptors are located and where they form synapses with SP terminals. In the superficial layers of the dorsal horn, the NK1 receptors appeared mainly of dendritic nature and were, like SP, abundant. In the deep layers of the dorsal horn and in the ventral horn, they were associated mostly with cell bodies. PMID- 1283532 TI - Chronic NO synthase inhibition fails to protect hippocampal neurones against NMDA toxicity. AB - Since nitric oxide (NO) is supposed to mediate excitotoxicity in various brain structures, the effects of two NO synthase inhibitors were studied on rat hippocampal lesions induced by the focal injection of N-methyl-D-aspartate (NMDA). Although both drugs (NG-nitro-L-arginine methyl ester: L-NAME and L-NG nitroarginine: L-NOARG) were given twice daily for 4 days before NMDA injection, at doses which are known to profoundly inhibit NO synthase activity, no significant decrease of NMDA-induced damage could be observed. These results do not confirm the current hypothesis of a NO involvement in NMDA toxicity at least on hippocampal neurons, in vivo. PMID- 1283533 TI - Accelerated expression of cholecystokinin gene in the brain of rats rendered tolerant to morphine. AB - Results from behavioural studies have shown that central cholecystokinin octapeptide (CCK-8) is a powerful antagonist against opioid effects and that an increased release of central CCK-8 plays an important role in the mechanisms of tolerance to morphine analgesia. No information is available concerning the rate of biosynthesis of CCK-8 in response to chronic morphine administration. Blot hybridization experiments made in the present study revealed a marked increase in preproCCK mRNA in the brain of rats receiving chronic morphine treatment for 1, 3 and 6 days, showing an increment of 52% (p < 0.05), 62% (p < 0.05) and 97% (p < 0.01) respectively. The results suggest that an acceleration of the expression of the CCK gene during long-term morphine treatment might constitute one of the mechanisms for morphine tolerance. PMID- 1283534 TI - U-50,488H into A10 reduces haloperidol-induced elevations of accumbens dopamine. AB - Injections of kappa (k) opioid agonists into the A10 ventral tegmental area (VTA) induce behavioral inhibitions and decreased interest in incentive stimuli, behavioral changes indicative of decreased mesolimbic dopamine (DA) transmission. In seeming contrast, three separate laboratories have recently reported that intra-VTA injections of k agonists do not affect nucleus accumbens septi (NAS) basal levels of extracellular DA. In the present experiment, we investigated whether intra-VTA injections of a k agonist would decrease pharmacologically stimulated increased levels of extracellular NAS DA. It was found that intra-VTA injections of the k agonist U-50,488H significantly attenuated haloperidol induced elevations of DA, as measured by in vivo microdialysis. PMID- 1283535 TI - The trophic effect of beta-amyloid 25-35 peptide is not mediated by NK1 or bombesin receptors. AB - beta-Amyloid peptide and spantide have previously been described to have trophic effects on hippocampal neurones in vitro. We report here that bombesin and [Pro9] substance P also show a neurotrophic effect on cultured hippocampal neurones. The neurotrophic effect of spantide or a beta-amyloid fragment containing amino acids 25 to 35 was not blocked by addition of the NK1 receptor agonist, substance P or the nonpeptide NK1 antagonist, RP 67580. For the bombesin-related peptides, the antagonist [Tyr4-DPhe12]-bombesin also provokes a trophic response, but the agonist alytesin and the antagonist [Leu13-psi-(CH2NH) Leu14]-bombesin have no effect on neurite growth. These results suggest that the observed trophic responses are unlikely to be mediated by a classical NK1 or bombesin receptor. PMID- 1283536 TI - Modulatory role of substance P on gonadotropin and prolactin secretion in the rabbit. AB - Substance P (SP) is present in large quantities in the brainstem and hypophysiotropic areas of the brain, but its roles in gonadotropin and prolactin secretion are controversial. The aim of this study was to measure luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) release from the pituitary after either intracerebroventricular (ICV) injection or infusion of SP or its C- and N-terminal fragments in intact (INT) and ovariectomized (OVX) conscious rabbits. A single injection of SP into the 3rd cerebral ventricle (3CVT) in INT and OVX rabbits augmented plasma LH concentrations, especially when SP was applied during the initial phase of an LH peak. Injection of SP during the declining phase of LH release was not effective. Injection of SP into the 3CVT was followed by increased plasma PRL concentrations in OVX but not in INT rabbits. Both SP 1-11 and SP 1-7 failed to alter LH, FSH, and PRL secretion when the peptides were slowly infused into the 3CVT, although ICV infusion of SP 6-11 did cause a delayed increase in LH release. The results support a stimulatory role of SP on LH and prolactin release. The results further indicate that although the stimulatory effect of SP on LH is ovarian steroid independent, in the absence of ovarian steroids, SP is stimulatory only during the rising phase of an LH pulse. A dual role of SP-ergic transmission in modulating LH secretion is discussed. PMID- 1283537 TI - [Palliative interventions]. AB - The German Gastric Cancer TNM Study included 1335 patients, of whom 657 (49.2%) underwent palliative surgery. The rate of resection was 50.6%. Postoperative complications occurred twice as often after palliative resectional surgery than after non-resectional procedures. In contrast, operative mortality rates did not differ. The median time of survival was 3 months after non-resectional procedures and 11 months after palliative resections. A considerable restriction of the quality of life occurred 2-3 months before death in both patient groups. Therefore, patients with non-resectional surgery hardly profit from the operation. PMID- 1283538 TI - [Conservative, palliative therapy of malignant pleural mesothelioma]. AB - No effective conventional therapy for malignant pleural mesothelioma has yet been described. Radiotherapy does not increase median survival, but there is a palliative analgesic benefit. Chemotherapy with a different regimen in 182 patients led to a median survival time of 12 months. In comparison to an untreated historical group of 142 patients, there is an advantage in survival of 5 months. Additional surgical treatment has not prolonged the life expectancy. The percentage of long-time survivors was 5.5%. PMID- 1283539 TI - [Conservative therapy of malignant pleural effusion]. AB - The nonsurgical treatment of malignant pleural effusion is palliative in principle. This aim must be achieved with a minimum of side effects and risks to the patients. Before treatment, a clear histologic diagnosis must be made. Thoracoscopy offers a fast and safe result with a more than 90% reliability. Systemic cytotoxic treatment and local procedures are available. Using pleurodesis, talkum is clearly superior to tetracycline in achieving a very low recurrence rate. The median survival in 287 patients was 9 months. PMID- 1283540 TI - [Pelvic multivisceral resection from the viewpoint of gynecology]. AB - The pelvic exenteration procedure must be considered a multimodal therapeutic concept from a humanistic-medical point of view. Careful patient selection, radical resection of all tumor-infiltrated organs, complete interdisciplinary organ reconstruction, and optimal perioperative management including full psychosomatic rehabilitation are mandatory. This concept should only be realized in medical centers with highly sophisticated infrastructures. PMID- 1283541 TI - Activation of Ca(2+)-dependent currents in cultured rat dorsal root ganglion neurones by a sperm factor and cyclic ADP-ribose. AB - The effects of intracellular application of two novel Ca2+ releasing agents have been studied in cultured rat dorsal root ganglion (DRG) neurones by monitoring Ca(2+)-dependent currents as a physiological index of raised free cytosolic Ca2+ ([Ca2+]i). A protein based sperm factor (SF) extracted from mammalian sperm, has been found to trigger Ca2+ oscillations and to sensitize unfertilized mammalian eggs to calcium induced calcium release (CICR). In this study intracellular application of SF activated Ca(2+)-dependent currents in approximately two-thirds of DRG neurones. The SF induced activity was abolished by heat treatment, attenuated by increasing the intracellular Ca2+ buffering capacity of the cells and persisted when extracellular Ca2+ was replaced by Ba2+. In addition, activity could be triggered or potentiated by loading the cells with Ca2+ by activating a series of voltage-gated Ca2+ currents. Ca(2+)-activated inward current activity was also generated by intracellular application of cyclic ADP-ribose (cADPR), a metabolite of NAD+, which causes Ca2+ release in sea urchin eggs. This activity could also be enhanced by loading the cells with Ca2+. The cADPR induced activity, but not the SF induced activity, was abolished by depleting the caffeine sensitive Ca2+ store. Ruthenium red markedly attenuated SF induced activity but had little action on cADPR induced activity or caffeine induced activity. Our results indicate that both SF and cADPR release intracellular Ca2+ pools in DRG neurones and that they appear to act on subtly distinct stores or distinct intracellular Ca2+ release mechanisms, possibly by modulating CICR. PMID- 1283542 TI - Automated multiple peptide synthesis. AB - A fully automated instrument for multiple simultaneous peptide synthesis was constructed to provide large numbers of peptides for immunological research. The synthesis is performed in a flow-through mode with the conventional solid supports contained in 48 individual reaction columns. The instrument is based on a commercial autosampler equipped with a motor-driven syringe for accurate delivery of reagents and a robot arm carrying a dispenser needle. Dedicated software was developed to compile overlapping peptides from a given protein sequence and to control all functions of the robot. In situ activation by BOP was chosen as the optimized chemistry protocol. The peptides are cleaved from the resin in the reactors used for synthesis, thus minimizing handling. Performance of the instrument was demonstrated by synthesis of overlapping 14-mer peptides derived from the sequence of HIV reversed transcriptase. A second mode of operation allows the synthesis to be carried out on the surface of polyethylene pins. Peptides derived from the sequence of human TNF were synthesized using this method and used to characterize antibodies raised against the intact protein. PMID- 1283543 TI - Heterosexual transmission of hepatitis C virus in family groups without risk factors. PMID- 1283544 TI - Colony-stimulating factor (CSF)-dependent growth of two leukemia cell lines. AB - The progressive accumulation of leukemic cells in acute myeloblastic leukemia (AML) results from the self-renewal capacity of leukemic blast progenitors. The growth of leukemic blast progenitors is supported by growth factors and colony stimulating factors (CSFs) have been shown to stimulate this phenomenon in vitro. After repeated subculture of leukemic cells obtained from a patient with AML M4 in the presence of recombinant G-CSF, a cell line dependent on G-CSF was established. This cell line, designated OCI/AML1a, does not respond to GM-CSF, interleukin-3 (IL-3), IL-1 or stem cell factor as well as G-CSF. The stimulatory effect of G-CSF on OCI/AML1a cells is almost completely blocked by monoclonal anti-G-CSF antibody. With G-CSF added in the culture, the OCI/AML1a cell line has been growing exponentially for over 5 years now. Another cell line, with growth dependent on IL-3, has also been established from a patient with chronic lymphocytic leukemia in the acute phase. This cell line TMD2 does not respond to G-CSF, GM-CSF, IL-1, or stem cell factor and anti-IL-3-antibody blocks the stimulatory effect of IL-3 on these cells. Receptors for IL-3 have been found on the surface of TMD2 cells. Although the TMD2 cell line is not derived from AML, the novel character of IL-3-dependency provides useful information for the study of the role of growth factor(s) in leukemic cell proliferation. These two CSF dependent cell lines are expected to be excellent models for the investigation of the precise mechanism by which G-CSF and IL-3 stimulate the growth of leukemic cells. PMID- 1283545 TI - The prognostic significance of the CD34 antigen in acute myeloid leukaemia. AB - The prognostic value of CD34 expression on leukaemic blast cells was assessed in 38 patients with acute myeloid leukaemia. Nineteen patients had more than 10% CD34 positive blast cells. Median survival for the CD34 positive patients was 125 days and for the CD34 negative patients the median survival has not yet been reached at day 575 (p = 0.06). Of those patients who received intensive chemotherapy, CD34 positive patients (n = 13) had a median survival of 150 days while for CD34 negative patients (n = 14) the median survival has not yet been reached (p = 0.01). Adjustment for age and pre-existing myelodysplastic syndrome did not affect the correlation of CD34 positivity with survival (p = 0.02). Over the period of observation (median 10 months, range 2-19 months) the relative risk of death was 5 times greater for the CD34 positive patients. This study suggests that CD34 expression is an adverse prognostic marker, independent of age and pre existing myelodysplasia. PMID- 1283546 TI - The clinical significance of cytokines and soluble forms of membrane-derived activation antigens in the serum of patients with Hodgkin's disease. AB - In a search for specific serum markers with prognostic impact in Hodgkin's Disease (HD), we evaluated the clinical significance of several cytokines (IL-1 beta, IL-2, IL-3, IL-6, G-CSF, GM-CSF, TNF-alpha) and soluble forms of membrane derived antigens (sCD4, sCD8, sCD23, sCD25, sCD30) in the serum of patients with untreated HD. Elevations of three groups of serum factors were observed: Firstly, elevations of the hematopoietic cytokines GM-CSF (detected in 39%), IL-6 (57%) and IL-3 (13%), which occurred simultaneously in the majority of the cases; secondly, simultaneous elevations of the inflammatory cytokines TNF-alpha and IL 1 beta (detected in 7%); and finally, elevations of membrane-derived activation antigens sCD8, sCD25, and sCD30. While the cytokine levels did not correlate with other obvious parameters, the membrane-derived activation antigens sCD8, sCD25 and sCD30 were associated with a poor prognosis. Only sCD30 correlated with disease activity and holds promise for the follow-up of patients in remission. Further investigations of these parameters at the cellular level might help to elucidate the enigmatic biology of HD. PMID- 1283547 TI - The current position of allogeneic and autologous BMT in multiple myeloma. AB - The projected outcome of allogeneic BMT for myeloma based on the EBMT data is as follows: for patients transplanted after first line therapy there is a 30% risk of transplant related death, a 55% chance of being alive at 5 years and a 35% chance of being alive in complete remission at 5 years. If BMT is performed later in the course of the disease, the risk of transplant related death is increased and the chance of long term relapse-free survival correspondingly reduced. Conversely, ABMT has a low mortality risk, but there is currently no evidence that ABMT using unpurged marrow can produce long term cure as no series has shown any evidence of a plateau in remission duration. The early results of maintenance interferon are encouraging but longer follow-up is needed to determine whether the proportion of patients in continuing remission at 5 years will approach that seen after allogeneic BMT. Early results of peripheral blood stem cell transplantation are also encouraging but longer follow-up is required. It remains extremely important when comparing results of ABMT with chemotherapy alone to compare similar patient groups, bearing in mind that patients who have autologous transplantation in first response are by definition responders with good performance status and without significant renal failure. In order to address this problem in a prospective manner, a randomised study has been planned by the EORTC in collaboration with the EBMT. In this study, patients with adequate renal function will be randomised at diagnosis to chemotherapy followed by either autologous BMT or continuing chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283548 TI - Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia. PMID- 1283549 TI - Clinical applications of haemopoietic growth factors. PMID- 1283550 TI - Down regulation of stem cell colony formation by purified CD8 lymphocytes and CD8 conditioned medium: potential importance for bone marrow transplantation in leukemia. AB - A methodology for selection of the CD8 cell subset from the peripheral blood and bone marrow mononuclear cells was developed using anti-T8 (CD8) antibody and magnetic microspheres coated with anti-mouse IgG. Following optimization of antibody:cell binding ratio and microsphere:cell ratios, CD8(+)-cells in the peripheral blood and bone marrow were effectively removed, with an overall final recovery of 34.9% +/- 8.6%, and 56% +/- 8.5% respectively with complete recovery of stem cells and very little contamination with effector cells. CD8(+)-depleted cell preparations demonstrated a 3-4 fold increase in CFU-C and CFU-E colony formation over non-depleted preparations when stimulated with G-CSF, GM-CSF or IL 3 and erythropoietin. The largest increase in colony formation was evident when IL-3 was used to stimulate colony formation. Purified autologous CD8+ T-cells or culture supernatant from in vitro cultures of purified autologous CD8+ T-cells added back to CD8 depleted preparations, induced 20%-90% suppression of CFU-C and CFU-E colony formation in a dose dependent manner. Colony formation by CD34+ cells, purified by anti CD34 antibodies and magnetic microspheres, were also inhibited by either pure CD8(+)-cell populations or CD8-culture supernatant. Preliminary fractionation studies indicate that the inhibitory factor is a protein of > 50 kd. In contrast, when purified autologous CD4+ cells were added to purified CD34+ stem cells, an increase (< 50%) in colony formation was observed. These results, taken together, suggest that CD8+ T-cells are negative effectors of normal hematopoiesis whereas CD4+ T-cells function as positive effectors. PMID- 1283551 TI - Multidrug resistance in acute leukemia: a conserved physiologic function. AB - Native resistance to conventional chemotherapy remains an important cause of treatment failure in the adult acute leukemias. Delineation of cellular mechanisms of drug resistance therefore represents a prerequisite to the development of more effective treatment strategies. The multidrug resistance (MDR) phenotype represents one such mechanism of resistance with direct clinical relevance. This phenotype occurs normally in certain mammalian tissues, and is detectable in tumor cell lines selected for resistance to naturally occurring antineoplastics. The mdr1 gene or its glycoprotein product, P-glycoprotein, is detected with high frequency in secondary acute myeloid leukemia (AML) and poor risk subsets of acute lymphoblastic leukemia. In prospective studies in AML, MDR overexpression is an independent determinant of response to treatment and overall survival with conventional-dose induction regimens. Investigations of mdr1 regulation in normal hematopoietic elements has shown a pattern which corresponds to its regulation in acute leukemia, explaining the linkage of mdr1 to specific cellular phenotypes. Therapeutic trials are now in progress to test the ability of various MDR-reversal agents to restore chemotherapy sensitivity in high-risk acute leukemias. PMID- 1283552 TI - Patient-controlled analgesia for older adults. AB - Use of patient-controlled analgesia (PCA) was compared with nurse-administered intermittent intramuscular (IM) injections of morphine in older adults during their postoperative recovery. Data analyses indicated that the PCA and IM groups did not differ in pain intensity, pain distress, and satisfaction. The PCA group had significantly less sleep disturbance from pain than the IM group. Neither group was considered to have acceptable pain management. PMID- 1283553 TI - The postoperative pain experience: a description based on the McGill Pain Questionnaire. AB - In surgical nursing practice, postoperative pain is of particular concern because of its documented effect on recovery and behaviors associated with recovery. Yet, little is known about the nature of this pain, other than its intensity. In this study, a description of the nature of the postoperative pain experience was generated from analysis of patient responses to the McGill Pain Questionnaire in four nursing intervention studies. The combined sample included 246 adult cholecystectomy patients. Patient descriptions of pain on the third postoperative day suggest a circumscribed sensory experience of moderate intensity. Sensory descriptors selected reflect two levels of noxious stimulation, one at the deeper somatic level (e.g., throbbing, stabbing, cramping, pulling, and burning) and one at a more superficial level (e.g., pricking, sharp, pinching, itching, sore, and tender). Descriptors of deeper pain tended to reflect greater intensity. The overall experience was characterized by 16 descriptors, selected by more than 30% of the sample and reflecting sensory, affective, and evaluative dimensions of the pain experience. Comparison of the findings from this combined sample drawn from hospitals in the northeastern United States were remarkably similar to those reported by Taenzer in Canada. The descriptors selected support, extend, and validate the kind of "sensation information" needed in preoperative instruction used in nursing practice and for abdominal surgery and can be useful in the assessment and management of postoperative pain. PMID- 1283554 TI - Educational technology: the basics and beyond. PMID- 1283555 TI - Slow potentials activated by afferent and direct stimulation in spinal interneurons of laminae III-V. AB - Stimulation of hairy skin afferent fibers and/or direct depolarizing current injection initiates persistent changes in membrane potential (slow potentials), lasting up to 1 min or longer, in some deep dorsal horn neurons. Intracellular staining with horseradish peroxidase shows that these cells are interneurons, suggesting that slow potentials modulate moment-to-moment impulse transmission in local spinal circuits. PMID- 1283556 TI - Substance P stimulates IL-1 production by astrocytes via intracellular calcium. AB - There is increasing evidence that local substance P (SP) exacerbates peripheral inflammations, partly by stimulating production of inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). SP may play similar roles in certain central nervous system inflammations. Multiple sclerosis plaques, for example, form around veins which are innervated by unmyelinated SP containing fibers, and astrocytes in multiple sclerosis plaques stain for SP. We tested whether SP could stimulate IL-1 and TNF alpha production by cultured astrocytes and whether calcium was the second messenger in this process. We found that both SP and the calcium ionophore A23187 raised intracellular calcium ([Ca2+]i) and stimulated IL-1 production in astrocytes. SP also nonsignificantly increased TNF alpha production by astrocytes. Treatment with dibromo BAPTA/AM, an intracellular calcium buffer, blocked SP-induced IL-1 production. These findings indicate that SP induces IL-1 production by astrocytes and uses calcium as a second messenger. Our results indicate local SP may play a role in multiple sclerosis and certain other central nervous system inflammations. PMID- 1283557 TI - Evidence that [3H]glutamate binding sites are masked by biologically relevant endogenous factor on cell membranes of frog spinal cord. AB - We identified the possible endogenous factor effective to modulate the binding of [3H]-labeled excitatory amino acid agonists and antagonists in the 100,000 x g supernatant of Triton X-100 (0.01%)-treated cell membranes from frog spinal cords. The factor inhibited the binding of [3H]glutamate to Triton X-100-treated cell membranes, to which the binding capacity of [3H]glutamate increased much more than that to intact cell membranes. The binding capacities of [3H]AMPA (an AMPA type agonist) and [3H]CPP (an NMDA type antagonist) to cell membranes remained low by Triton treatment, but they were enhanced significantly by the addition of the factor. The effect of the factor on the [3H]kainate binding was hardly observable. The factor may provide key information on receptor structures and the classification of receptor types concerning excitatory amino acids in the mammalian central nervous system. PMID- 1283558 TI - Numerous SP-positive pyramidal neurons in cat neocortex are glutamate-positive. AB - An immunocytochemical technique that allows visualization of two antigens in the same neuron was used to verify the possibility that some neocortical pyramidal neurons contain both glutamate (Glu) and substance P (SP) immunoreactivity. The results show that a large fraction of SP-positive pyramidal neurons are also Glu positive, and indicate that in a small population of cortical neurons a fast excitatory synaptic transmitter and a slow peptidic modulator coexist. PMID- 1283559 TI - Impact of a galanin antagonist on exogenous galanin and natural patterns of fat ingestion. AB - The peptide galanin (GAL) has a potent stimulatory effect on fat ingestion after administration into the hypothalamic paraventricular nucleus (PVN). This study examined a newly synthesized GAL antagonist, M40, in two separate experiments involving: (1) PVN injections of M40 alone in freely feeding animals, to investigate the importance of endogenous GAL receptor activity in determining natural patterns of fat ingestion, and (2) PVN injections of M40 in combination with exogenous GAL, to determine whether endogenous GAL receptors mediate this peptide-induced response. The results demonstrate that PVN injection of M40 by itself dose-dependently (2-108 pmol) reduces spontaneous ingestion of the fat diet. This phenomenon is robust, behaviorally specific and opposite to that induced by GAL itself. Moreover, the stimulatory effect of PVN-injected GAL on fat ingestion can be blocked by prior PVN administration of M40 at relatively low doses (2-6 pmol), indicating that M40 is a potent antagonist of GAL receptors in the hypothalamus. Together, these results provide the first evidence for the existence of endogenous GAL receptors in mediating the action of exogenous GAL in the hypothalamus. They also constitute a crucial step in demonstrating a physiological function of these PVN GAL receptors in controlling natural patterns of fat ingestion. PMID- 1283560 TI - Axonal flow blockade induces alpha-CGRP mRNA expression in rat motoneurons. AB - Axonal flow of motoneurons was blocked in the sciatic nerve by the application of vinblastine at a low concentration (100 microM) not considered likely to cause axonal degeneration. The number of motoneurons expressing alpha-calcitonin gene related peptide (CGRP) mRNA was significantly increased by vinblastine application, while the expression of beta-CGRP mRNA was not influenced. These findings suggest that the synthesis of these two peptides is differentially regulated and that alpha-CGRP mRNA is possibly down-regulated by unknown factor(s) which normally undergo retrograde transport from the periphery. PMID- 1283561 TI - Decrease of enkephalins in cerebellum during Wobbler mouse motoneuron disease. AB - The Wobbler mouse possesses an inherited motoneuron disease, which expresses itself primarily at cervical spinal levels and in cranial motor nuclei. Cell degeneration is sporatic and negligible in other motor regions of the brain (e.g., cerebellum, corpus striatum). However, enkephalin concentrations are consistently lower in the Wobbler cerebellum throughout the motoneuron disease, whereas substance P concentrations are significantly higher late in the disease compared with the normal phenotype littermates. The data imply that early changes in enkephalin (also shown for leucine enkephalin in the spinal cord and brainstem) may be important to the etiology of the Wobbler disorder. Like the late increase of substance P, this may reflect a yet-to-be described response to parent cell degeneration in the raphe nuclei. TRH remained unchanged in Wobbler cerebellum and corpus striatum, wherein the other peptides studied herein also maintained similar concentrations to the normal phenotype littermates. PMID- 1283562 TI - Differential projections to the superior collicular layers from the perihypoglossal nuclei in the cat. AB - The primary objective of the present study is to demonstrate the presence of a projection to the superficial layers of the superior colliculus (SC) from the perihypoglossal nuclei, specifically from the nucleus intercalatus (INT) in the cat. Iontophoretic application of WGA-HRP into the perihypoglossal complex produced orthogradely labeled terminals in the SC contralaterally forming two bands: one is in the superficial gray layer, and the other in the intermediate gray layer. The superficial band was evenly distributed in the upper portion of the superficial gray layers (layers II1-2) and the deeper band existed in the intermediate gray layer (layer IV) being arranged in a discontinuous manner. Injections of the tracer into the superficial layers of the SC yielded retrogradely labeled cells only in the rostral part of the contralateral INT; by contrast, the injection confined to the deep layers produced labeling of cells exclusively in the nucleus prepositus hypoglossi (PH). Thus, the INT and the PH each project separately to the functionally different superficial and intermediate layers of the SC, respectively. On the basis of the present anatomical findings, it is suggested that the perihypoglossal nuclei as a whole contribute not only to the oculomotor but also to the visuosensory regulatory function in the SC. PMID- 1283563 TI - Intrathecal oxymetazoline does not produce neurotoxicity in the spinal cord of the rat. AB - To determine if intrathecal (i.t.) oxymetazoline (OXY) induces histological evidence of spinal neurotoxicity, male, Sprague-Dawley rats (300-450 g; implanted with an i.t. catheter) were treated with i.t. saline or 100 nmol OXY twice daily for 3 days, or 200 or 300 nmol OXY once daily for 3 days. Spantide (D-Arg1, D Try7,9, Leu11-substance P; 0.067 nmol = 0.1 microgram, 0.167 nmol = 0.25 microgram or 0.334 nmol = 0.5 microgram) or capsaicin (0.164 mumol = 50 micrograms), given as a single i.t. injection, were used as positive controls. Animals were killed 12 h after the last injection of saline or OXY, and 72 h after spantide or capsaicin. Spinal cord sections (L1 and adjacent segments) were examined by light microscopy for changes in gross morphology, substance P-like immunoreactivity (SP-IR) and calcitonin gene related peptide-like immunoreactivity (CGRP-IR). All doses of i.t. OXY produced antinociception (tail flick ED50 = 53.7 nmol, paw pressure withdrawal ED50 = 93.3 nmol). Rectal temperature decreased by 1.5-2.4 degrees C up to 12 h after 100 nmol of i.t. OXY. There were no signs of inflammation or necrosis, and no detectable loss or damage to either spinal afferents or motor neurons as judged by SP-IR and CGRP-IR structures in spinal cords of OXY-treated animals (all doses) as compared to i.t. saline controls. Spantide (0.1 microgram) had no antinociceptive or neurotoxic effect; 0.25 microgram induced irreversible loss of the TF reflex and transient hind limb paralysis; 0.5 microgram induced irreversible loss of TF and PP responses, permanent hind limb paralysis, bladder and bowel dysfunction. The spinal cords from these animals showed signs of extensive necrosis, cavitation, and haemorrhage in the ventral horn accompanied by a loss of CGRP-IR motor neurons. Capsaicin-treated rats exhibited a permanent loss of the TF but not the PP response and a marked reduction of SP-IR spinal afferents in the dorsal horn. It is concluded that i.t. OXY produces antinociception in the rat with no detectable spinal neurotoxicity as assessed by parameters which are sensitive to the neurotoxins, spantide and capsaicin. PMID- 1283564 TI - [Inhibition by pentoxifylline of procoagulant activity produced by endotoxin active monocytes]. AB - When appropriately stimulated, monocytes are able to initiate blood coagulation through the membrane expression of tissue factor. This procoagulant activity is thought to play a role in activating coagulation in response to inflammatory stimuli in vivo. We found that pentoxifylline, a methylxanthine derivative already reported to regulate some monocyte functions, inhibits the procoagulant activity developed by monocytes in vitro in response to endotoxin. This effect was accompanied by an early increase in intracellular levels of cyclic AMP and was mimicked by compounds that induce an increase in cyclic AMP levels. These results suggest that the suppressive effect of pentoxifylline occurs at least in part via an increase in intracellular cyclic AMP levels. PMID- 1283565 TI - X-inactivation in girls with Rett syndrome. AB - Cytogenetic studies have been carried out on a series of nine girls with Rett syndrome, six of their mothers and nine normal female controls. No abnormality of the X-chromosome has been observed in any subject. X-inactivation studies using various methods of detecting the timing of individual band replication were performed. The overall pattern seen was essentially the same in all subjects, but in the patients with Rett syndrome there may be an alteration in the timing of the X-inactivation process in the region Xp11.3 or 4-->Xp21. PMID- 1283566 TI - Analysis of CA/GT microsatellite polymorphism in IVS8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a study of Italian CF families. AB - Forty-six CF Italian patients and their parents were screened for a highly polymorphic microsatellite consisting of a variable number of CA/GT repeats in intron 8 of the CFTR gene. A strong degree of association was found between alleles 2 and 6 and the CF mutation delta F508. Moreover, considering the haplotypes at the closely linked locus D7S23 and the microsatellite's alleles, a strong linkage disequilibrium was again found for delta F508 and also for non delta F508 CF chromosomes and the eight commonest haplotypes (B2, B6, C7, A6, A7, B7, D2 and D7). These data, compared with those described in the Spanish population, further support the common origin of the delta F508 mutation in Southern European populations. PMID- 1283567 TI - Quantification of the in vitro activity of some compounds with spermicidal activity. AB - The in vitro spermicidal activity of the commonly used surfactant spermicides and the antiseptic chlorhexidine, were quantified in a statistically reproducible manner, using donor semen and image capture analysis. The spermicidal activity was expressed as the ED50 under defined assay conditions. Using these parameters, the order of spermicidal activity was: Menfegol > nonoxynol-9 approximately benzalkonium chloride > sodium docusate > chlorhexidine. These differences were statistically significant. PMID- 1283568 TI - A comparative study of allergenic and potentially allergenic enzymes from Dermatophagoides pteronyssinus, D. farinae and Euroglyphus maynei. AB - The presence of the enzymatically active allergens equivalent to Der p I (cysteine protease), Der p III (serine protease) and amylase in extracts of Dermatophagoides pteronyssinus, D. farinae and Euroglyphus maynei was determined using appropriate enzymatic techniques. Biochemical equivalents of all three allergens were present in each extract studied. Studies also showed that the mite extracts contained a variety of other biochemically active enzymes including trypsin, chymotrypsin, carboxypeptidase A and B, glucoamylase and lysozyme. Marked differences in the relative concentrations of some of these enzymes in different mite extracts were observed, particularly trypsin and carboxypeptidase A. The enzymes were physicochemically similar to equivalent enzymes from vertebrate and invertebrate sources. Chromatofocusing studies of faecal extracts derived from D. pteronyssinus and D. farinae showed that several isoforms of each enzyme were present. The data indicated that there were more trypsin isoforms, with pI over a wider range, in extracts prepared from D. pteronyssinus. Proteases and carbohydrases were also found in extracts prepared from faecally enriched material suggesting that they were endoperitrophic and associated with mite digestion. The data suggest that not only are the group I, III and amylase allergens a consistent feature of most pyroglyphid dust mites but also that other proteases and carbohydrases present in mite faeces are allergenic. PMID- 1283569 TI - Metabolism of a new HIV-1 reverse transcriptase inhibitor, 3-[2-(benzoxazol-2 yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (L-696,229), in rat and liver slices. AB - L-696,229 is a potent and specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and is currently undergoing clinical evaluation. In vivo metabolism in rats was investigated using an intravenous bolus dose of 5 mg/kg [3H]L-696,229. The amount of radioactivity eliminated in bile and urine over a period of 6 hr was 60 and 22%, respectively. Radiochromatographic analysis of the bile and urine showed that L-696,229 was metabolized rapidly and completely to several common metabolites. Sequential oxidation at the alpha position of the 5-ethyl group to an acetyl moiety, aromatic hydroxylation of the benzoxazole group (position C4', C6', or C7'), and subsequent sulfate conjugation were the major metabolic pathways as determined by the application of enzymatic hydrolysis, FAB-MS, and 1H- and 13C-NMR spectroscopies. The in vitro metabolism of this 2-pyridinone derivative with rat liver slices resulted primarily in hydroxylation at the 6-methyl and 5-ethyl groups. The 6-hydroxymethyl- and 5 alpha-hydroxyethyl analogs were also inhibitors of HIV-1 reverse transcriptase. PMID- 1283570 TI - Comparative efficacy, safety and pharmacokinetics of verapamil SR vs verapamil IR in hypertensive patients. AB - The antihypertensive effects of the regular immediate release formulation of verapamil (verapamil IR) and the newer sustained release formulation of verapamil (verapamil SR) were compared in Hispanic patients with untreated essential hypertension. Verapamil IR was given in 3 divided doses (80 or 160mg 3 times daily) and verapamil SR was given either as a single daily dose of 240mg or as 240mg every 12 hours. With both formulations there was a significant reduction in systolic (SBP) and diastolic blood pressure (DBP); a greater lowering of BP was observed with verapamil 480 mg/day than with 240 mg/day. With verapamil SR 480 mg/day, 91% of patients had reductions in SBP and DBP greater than 20 and 15mm Hg, respectively. In addition, 83% of patients reached normotension. With the lower dose (240mg once daily), 83% of patients had decreases in DBP greater than 10mm Hg and 73% of patients achieved normotension. Comparable effects were achieved with verapamil IR. With verapamil IR there was a more rapid fall in BP which peaked 3 to 4 hours postdose, whereas with verapamil SR a more gradual and sustained BP reduction was observed. Only small changes in heart rate (HR) were observed with verapamil IR and verapamil SR. For verapamil SR, the mean increase in HR was 5 beats/min (to 80 beats/min) and the mean decrease in HR was 13 beats/min (to 62 beats/min). Both verapamil SR and verapamil IR prolonged the PR interval of the ECG. An equal degree of PR prolongation was observed with 240 and 480 mg/day. The incidence of side effects (headache, palpitations, dizziness and flushing) was dose dependent, decreased with continuous treatment and was much higher with verapamil IR than with verapamil SR. Steady-state plasma verapamil concentrations were monitored. Compared with verapamil IR, verapamil SR produced a more gradual rise and a more sustained elevation of plasma verapamil and norverapamil concentrations. Comparable trough verapamil concentrations (Cmin) were observed with verapamil IR (98 micrograms/L) and SR (81 micrograms/L); morning Cmin verapamil concentrations were higher than daytime Cmin values. The normalised area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) were 10 to 20% greater for verapamil IR than SR. The 2-fold increase in oral dose produced a 2.2- and 2.4-fold increase in AUC for verapamil IR and SR, respectively, associated with a 20% reduction in metabolism to norverapamil. Fasting increased the rate and extent of absorption of verapamil.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1283571 TI - Use of cell culture for optimisation of direct antiatherogenic therapy with verapamil. AB - The potential of verapamil to prevent atherogenesis induced by atherogenic serum in cell culture was investigated. Smooth muscle cells were cultured from human aortic intima and incubated with blood serum from patients with coronary artery disease. Only serum causing a significant rise in total cholesterol content in cultured cells during a 24-hour incubation period was used. The addition of verapamil to cells decreased serum-induced cholesterol accumulation. The maximum antiatherogenic effect of verapamil in vitro was recorded at 10(-5) to 10(-4) mol/L. Blood serum obtained from patients before and after oral verapamil administration was added to cultured cells. The atherogenic potential of serum obtained after verapamil administration was significantly lower than the predose value. To optimise direct antiatherogenic therapy with verapamil, the minimum dose that produced the maximum effect was established as 30 to 40mg. Using a 40mg dose, the maximum effect of oral verapamil was observed 3 hours after administration. A second 40mg dose was given 5 hours after the first dose, when the blood serum atherogenic potential was about 40% of the predose value and rising. This second dose maintained the atherogenic potential of serum at about 40%. Thus, to decrease atherogenic potential of serum and to maintain it at a low level, verapamil should be administered at a dose of 40mg 5 times daily with a 4- to 5-hour interval between doses. PMID- 1283572 TI - Vascular calcium overload. Physiological and pharmacological consequences. AB - Pronounced vascular calcium overload, especially of compliance arteries, is an important aspect of aging, and of various age-related vascular diseases such as hypertension and atherosclerosis. The development of new drugs specifically aimed at attenuating the evolution and/or pathological consequences of vascular calcium overload is hindered by the paucity of animal models available. Although several laboratory animals exhibit vascular calcium overload, this evolves slowly and is far less marked than in man. Nevertheless, Fleckenstein and associates (1989) suggested a suitable animal model involving the treatment of young rats with vitamin D3 and nicotine; such treatment produces pronounced vascular calcium overload within a few weeks. This paper describes the cardiovascular effects of such treatment, and our preliminary attempts to pharmacologically modify vascular calcium overload and its cardiovascular consequences. PMID- 1283573 TI - Arterial calcinosis, chronic renal failure and calcium antagonism. AB - A progressive rise in arterial calcium content is the most characteristic age associated alteration in the arterial wall and the decisive factor in arteriosclerotic degeneration. Experimental studies have demonstrated that calcium antagonists can prevent or retard the development of arterial calcinosis associated with vitamin D overload, hypertension or alloxan-induced diabetes. Although similar effects are more difficult to observe in humans, they have been demonstrated in patients with coronary artery disease and in patients with end stage renal disease, which is characterised by an acceleration of the normal arterial aging process. PMID- 1283574 TI - Use of ambulatory blood pressure monitoring in the management of antihypertensive therapy. AB - The recent development of ambulatory blood pressure (ABP) monitoring techniques has improved recording of blood pressure in therapeutic trials and in the clinical setting. The application of ABP differs according to which of these 2 applications is being considered. In therapeutic trials, a placebo control is required. The large quantity of precise data acquired with ABP monitoring allows the study of a limited number of patients; it also allows individual study of patients with a 'white coat' response (i.e. elevated blood pressure in response to examination by the clinician). Analysis of data from ABP monitoring may include the following: comparison of mean blood pressure values over 24 hours, daytime or night-time, or over any other selected time period; 24-hour blood pressure profiles, or analysis hour-by-hour, giving true chronotherapy, and providing data regarding the wearing-off of a drug effect or loss of therapeutic control; analysis of blood pressure at particular times, such as on waking; or specific examination of nonresponders. In individual patients, ABP monitoring should be reserved for specific indications. It can be used before initiation of treatment to confirm the necessity for treatment, especially in the context of hypertension at rest or the 'white coat' effect. With established treatment, ABP monitoring can be used in patients with resistant hypertension, in severe hypertension to examine loss of blood pressure control over time or inversion of the day/night cycle, and in patients with a specific illness, e.g. diabetes, in order to obtain the lowest blood pressure readings possible. Examination of these factors assists clinicians to accurately decide upon the timing and frequency of antihypertensive therapy. PMID- 1283575 TI - Can the coronary atherosclerotic process be influenced by calcium antagonists? AB - Cell culture experiments and various animal models have shown that calcium antagonists can inhibit atheroma development. A number of antiatherosclerotic mechanisms have been proposed and the promising results of these in vitro and animal experiments prompted clinical trials. Retrospective analyses indicated that verapamil might retard disease progression and the development of new stenoses. Prospective clinical studies, however, have revealed no effect by calcium antagonists on pre-existing coronary stenoses (> or = 20%) and it is suggested that the study duration (2 to 3 years) may have been too short and that advanced stages of atheromatous disease are not influenced by calcium antagonists. Current data suggest that only early stages of coronary atheromatosis may be affected by treatment with calcium antagonists; however, optimum drug, dosage and suitable patients are yet to be defined. PMID- 1283576 TI - Preliminary clinical experience with calcium antagonists in atherosclerosis. Verapamil in Hypertension Atherosclerosis Study Investigators. AB - Animal experiments have shown that the administration of calcium antagonists can prevent or slow the progression of atherosclerosis by inhibiting calcium overload and interfering with lipid metabolism and deposition. These encouraging results have prompted clinical trials to evaluate the effects of calcium antagonists (dihydropyridines and diphenylalkylamines) on atherosclerotic plaque formation. In patients with coronary heart disease, several studies have already shown that calcium antagonists can have a positive effect on plaque evolution, while in hypertensive patients no such study has been published to date. The Verapamil in Hypertension Atherosclerosis Study is an ongoing multicentre randomised double blind parallel group trial comparing the antihypertensive efficacy of verapamil SR 240 mg/day with that of chlorthalidone 25 mg/day in 1464 patients with essential hypertension aged 40 to 65 years. In a randomised subgroup of patients (n = 550), who will be followed up for 3 years, B-mode ultrasonography is being employed to evaluate the effects of the 2 drugs on carotid wall thickness and carotid plaque development. Ultrasonographic evaluations are performed at baseline, after 3 months, and 1, 2 and 3 years after a standardised protocol to determine intimal-medial thickness in 4 segments of the extracranial carotid tree. The most interesting result to date is the high incidence of carotid alterations, with plaques present in 35% and arterial wall thickening in 31.8% of the 311 asymptomatic hypertensive patients processed so far. A preliminary evaluation of the antihypertensive efficacy of the trial medications after 6 months of double-blind treatment indicates a 63.5% response rate to monotherapy and a 7.8% drop-out rate because of drug inefficacy or intolerance. PMID- 1283577 TI - Quality of life in the treatment of hypertension. The effect of calcium antagonists. AB - The effects of calcium antagonists on psychological well-being, cognitive function, activity and physical symptoms in hypertensive patients are reviewed. Effects on these aspects of quality of life appear to differ according to whether a dihydropyridine calcium antagonist such as nifedipine is employed or verapamil, which is a phenylalkylamine derivative. Nifedipine has been associated with a self-assessment of impaired cognitive function in 2 clinical trials. Nifedipine was also associated with more symptomatic complaints than both atenolol and verapamil in different studies. The problems with nifedipine centred on oedema, flushing and palpitations. Verapamil was associated with constipation. Compared with other classes of antihypertensive drugs, the position of calcium antagonists with respect to the maintenance of patients' quality of life is presently unclear. Verapamil has been associated with improved quality of life compared with propranolol (a beta-blocker) and nifedipine. Verapamil appears to have similar effects on quality of life as atenolol and the angiotensin converting enzyme (ACE) inhibitor, captopril. The position of nifedipine remains unclear. PMID- 1283578 TI - Does a reduction in left ventricular hypertrophy reduce cardiovascular morbidity and mortality? AB - Left ventricular hypertrophy is an important risk factor for sudden death and other cardiovascular morbidity and mortality irrespective of the level of arterial blood pressure. Left ventricular hypertrophy, i.e. an increase in wall thickness at the expense of left ventricular volume, is an adaptive mechanism observed in patients with long standing arterial hypertension. Severe left ventricular hypertrophy is associated with a reduction in left ventricular compliance, impaired coronary reserve, ventricular ectopy, and impaired contractile function. Left ventricular hypertrophy can be reduced by antihypertensive therapy; however, not all antihypertensive agents have the same effect on left ventricular hypertrophy despite their similar effects on arterial blood pressure. Angiotensin converting enzyme (ACE) inhibitors appear to be the most powerful agents for reducing left ventricular hypertrophy, followed by the nondihydropyridine calcium antagonists. In addition to reducing left ventricular mass and arterial blood pressure, certain calcium antagonists also improve left ventricular filling, suppress ventricular ectopy, and maintain or enhance contractile function. However, despite these beneficial effects, it is not known whether the risk of cardiovascular morbidity and mortality can be prevented or reduced by specific antihypertensive agents. PMID- 1283579 TI - Choosing the correct drug for the individual hypertensive patient. AB - With the availability of a wide selection of antihypertensive drugs acting by different mechanisms, it should be possible to match the requirement of individual patients with the pharmacological and clinical properties of an appropriate agent. Although the concept of stepped-care therapy is now largely outdated, therapy must be initiated with one agent. Diuretics remain a first choice option in the elderly and in Black patients, as do calcium antagonists. In patients with ischaemic heart disease or enhanced adrenergic drive, beta-blockers are preferred. Calcium antagonists or ACE inhibitors are finding increasing use as initial therapy when quality of life is important and metabolic neutrality is required. The choice of antihypertensive agent may be limited by adverse effects, e.g. pedal oedema with nifedipine, constipation with verapamil, and cough with ACE inhibitors. Certain advantages are evident for both calcium antagonists and ACE inhibitors. Calcium antagonists are more likely to be effective first-line therapy than ACE inhibitors in Black patients, in those with a high salt intake, in patients with Raynaud's disease, and when angina pectoris is present. ACE inhibitors are preferred for use in combination with diuretic agents, and in the presence of congestive heart failure or low salt intake. Combination therapy between these 2 drug classes is finding increasing acceptance because of its many theoretical advantages, and may provide a means of maximising benefit. PMID- 1283580 TI - Ambulatory blood pressure monitoring. AB - This paper reviews the evidence that, in patients with hypertension, end-organ damage correlates more closely with blood pressure values obtained by ambulatory blood pressure monitoring than with those obtained by conventional sphygmomanometry. However, ambulatory blood pressure monitoring is not suitable for routine use in the clinical setting because of a lack of standard reference values and data regarding the prognostic significance of this method. Ambulatory blood pressure values are reproducible and this method avoids the so-called placebo effect; thus, this method is useful in clinical studies investigating the efficacy and duration of action of antihypertensive drugs. Data from 1 study in which hypertensive patients were treated with slow release verapamil 240 mg, enalapril 20 mg, nitrendipine 20 mg and placebo, given once daily for 8 weeks according to a double-blind parallel group design, showed that mean 24-hour ambulatory blood pressure was reduced by all 3 drugs compared with placebo. Verapamil and enalapril showed similar antihypertensive efficacy and both drugs reduced night-time blood pressure more effectively than nitrendipine. PMID- 1283581 TI - Calcium overload--an important cellular mechanism in hypertension and arteriosclerosis. AB - Arterial hypertension and arteriosclerosis are dramatic consequences of vascular calcium overload. Acute intracellular calcium overload of vascular smooth muscle cells produces hypercontractility. Hypertension develops if a general increase in systemic arteriolar tone leads to a rise in peripheral flow resistance. Moreover, progressive elevation of calcium destroys the structural integrity of the arterial and arteriolar walls. Thus, in various animals models, calcium overload initiates lesions of an arteriosclerotic character. Interestingly, conventional human coronary plaques also represent a calcium-dominated type of arteriosclerosis. With the advent of specific calcium antagonists, the pathogenic effects of calcium overload and its deleterious consequences have become, for the first time, accessible to therapeutic intervention. Accordingly, adequate treatment with calcium antagonists prevents calcium overload and can thereby protect arteries and arterioles from functional disturbances and structural damage. In spontaneously hypertensive rats, specific calcium antagonists of the verapamil, nifedipine and diltiazem type normalise blood pressure (BP) by reducing transmembrane calcium influx into vascular smooth muscle cells. However, in addition to controlling BP, these drugs also act as tissue protective agents. The long term effects of calcium antagonists such as verapamil in experimental hypertension include the prevention of severe arteriosclerosis, myocardial hypertrophy, and malignant nephrosclerosis. In humans, the antihypertensive efficacy of verapamil is well documented. Further clinical studies have yet to evaluate the antiarteriosclerotic and tissue protective potential of verapamil in humans. PMID- 1283582 TI - Secondary prevention with calcium antagonists after acute myocardial infarction. AB - Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival and preventing reinfarction, nevertheless demonstrated pronounced differences between the 3 drugs. Nifedipine had no effect on reinfarction or death. Diltiazem had no overall effect but prevented first reinfarction or cardiac death (cardiac events) in patients without heart failure, and increased cardiac events in patients with heart failure before randomisation. Verapamil prevented first reinfarction or death (major events); the most pronounced effect was found in patients without heart failure before randomisation. Verapamil did not have detrimental effects in patients treated for heart failure before randomisation. Differences between trials and between drugs explaining the different clinical findings are evaluated. PMID- 1283583 TI - Cardiac hypertrophy and aortic compliance after calcium channel antagonism in hypertension. AB - Calcium antagonists are potent vasodilators. They improve arterial compliance by their action at the level of the large arteries. Several experimental and clinical studies have shown decreases of varying magnitudes in hypertension induced cardiac hypertrophy after long term treatment. It appears that the mechanisms of this reduction in cardiac mass are complex. As arterial compliance is one of the determinants of left ventricular hypertrophy in hypertension, it may be considered that an improvement in cardiac mass can result not only from the blood pressure reduction but also from the increase in arterial compliance associated with calcium antagonist treatment in essential sustained hypertension. PMID- 1283584 TI - Regional myocardial blood flow and coronary reserve in hypertensive patients. The effect of therapy. AB - Patients with essential arterial hypertension demonstrate abnormal vasodilator capacity either during increased cardiac metabolic demand or during pharmacological vasodilation. Structural and functional damage to the coronary microcirculation has been proposed as one of the major causes of impaired coronary reserve in this disease. To assess the role of microvascular impairment in regional myocardial blood flow (MBF), 27 patients with essential hypertension were evaluated by dynamic positron emission tomography (PET) at rest, during atrial pacing and after dipyridamole infusion and compared with 13 healthy subjects. All patients had normal coronary arteries, 17 had moderate to severe hypertension and 10 had mild hypertension. Baseline mean MBF of 0.97 +/- 0.25 ml/min/g was significantly increased to 1.60 +/- 0.38 during atrial pacing and 2.35 +/- 0.95 after dipyridamole infusion (p < 0.01); however, mean flow during atrial pacing and after dipyridamole infusion was significantly lower than in healthy subjects (2.15 +/- 0.73 and 3.71 +/- 0.86 ml/min/g, p < 0.05 and p < 0.01, respectively). The MBF response to atrial pacing and dipyridamole infusion was similarly depressed in patients with mild and severe hypertension. The study was repeated after 6 months of antihypertensive treatment with the calcium antagonist verapamil or the angiotensin converting enzyme (ACE) inhibitor enalapril in a subgroup of 20 patients as part of a randomised, single-blind clinical trial. This study is still in progress; the initial 16 patients treated with verapamil or enalapril showed an obvious improvement in MBF values during atrial pacing and after dipyridamole infusion after 6 months of therapy (mean MBF: 2.10 +/- 0.64 and 2.99 +/- 1.63 ml/min/g, respectively, p < 0.05 vs pretreatment values). In conclusion, obvious impairment of MBF during atrial pacing and after dipyridamole infusion was observed in hypertensive patients with normal coronary arteries and this appeared unrelated to the severity of hypertension. Therapy with verapamil or enalapril improved coronary reserve and MBF response to an increase in myocardial oxygen demand. PMID- 1283585 TI - The J-curve. The importance of gradual reduction of blood pressure. AB - Even if the treatment goal in hypertension is 'the lower the better', it is obvious that blood pressure (BP) cannot be reduced without reaching a point at which organ perfusion may become compromised and where mortality and morbidity will increase rather than decrease. In 1979, a 5-fold increase in myocardial infarction among patients whose diastolic BP was reduced to below 95mm Hg was reported. In 1987, these results were confirmed, and a J-shaped relationship between diastolic BP and death from myocardial infarction in those patients with evidence of ischaemic heart disease at entry into the trial was shown. In recent years, several studies have demonstrated this J-shaped curve with a J-point between 85 and 91mm Hg. However, all the data were obtained in retrospective analyses of a small number of patients and prospective properly designed studies are necessary before changing our treatment criteria. The Behandla Blodtryck Battre Study fulfils these criteria and preliminary results demonstrate that it is possible to achieve a further reduction in BP in well controlled hypertensive patients without increasing the incidence of side effects. PMID- 1283586 TI - Is salt restriction necessary in hypertensive patients treated with calcium antagonists? AB - A moderate restriction of salt intake is recommended as a nonpharmacological approach to reducing high blood pressure, and can be used as an adjuvant to antihypertensive drug treatment. Noncompliance with a salt-restricted diet is the main limitation to this therapeutic approach. Evidence to date has shown that hypertensive patients treated with a calcium antagonist may not require a salt restricted diet to achieve target blood pressure reductions. Further long term studies are required to confirm this. PMID- 1283587 TI - Risk-benefit aspects of antihypertensive drugs. AB - Several long term trials using traditional antihypertensive therapy with diuretics and beta-blockers have shown that antihypertensive therapy reduces the overall risk of cardiovascular complications. However, even after several years of therapy the cardiovascular risk in hypertensive patients cannot be lowered to that in the normotensive population. Antihypertensive therapy can reduce the incidence of cerebrovascular complications in patients with hypertension by about 65%. However, the effect of such therapy in preventing coronary events has been disappointing, as these events are 3 to 4 times more common than cerebrovascular complications in hypertensive patients. It is now apparent that adverse pharmacological effects of diuretics and beta-blockers on lipid metabolism persist for many years. Thus, treatment with these agents constitutes a new risk factor for coronary heart disease and may, at least in part, explain the failure of traditional antihypertensive therapy to reduce the incidence of myocardial infarction and sudden death as effectively as that of cerebrovascular accidents. On the other hand, titration of these antihypertensive agents to the lowest possible dose in order to avoid metabolic alterations and subjective adverse effects has frequently resulted in the administration of subtherapeutic doses, particularly for hydrochlorothiazide. Until comparative long term clinical trials with older and newer antihypertensive agents and morbidity and mortality as end points are completed, the debate on first-line drugs for antihypertensive treatment will not be satisfactorily resolved. PMID- 1283588 TI - Swiss hypertension treatment programme with verapamil and/or enalapril in diabetic patients. AB - The purpose of the present study was to assess the efficacy and tolerability of diuretic-free antihypertensive therapy with a calcium antagonist and/or an angiotensin converting enzyme (ACE) inhibitor in patients with diabetes mellitus. 54 hypertensive [blood pressure (BP) above 140/90mm Hg] patients with diabetes mellitus type 1 (n = 7) or 2 (n = 47) and normal serum creatinine levels (mean 82 +/- 6 mumol/L) received either verapamil or enalapril after a 2-week washout and a 4-week placebo phase. If BP remained elevated, both agents were combined. Verapamil or enalapril alone normalised diastolic BP (to less than 90mm Hg) in 36 patients; verapamil decreased BP from 159/98 to 147/87mm Hg (n = 19, p < 0.001) and enalapril decreased BP from 166/99 to 146/88mm Hg (n = 17, p < 0.001). In 18 patients who remained hypertensive after 10 weeks of monotherapy, a combination of both drugs decreased BP from 169/104 to 151/90mm Hg (p < 0.001). Overall, 87% of patients achieved a target BP response at 30 weeks. Urinary albumin as related to creatinine excretion (UAE; micrograms albumin:mg creatinine) was on average not significantly changed after verapamil or enalapril treatment, alone or combined. Nevertheless, in patients with initial microalbuminuria, UAE decreased (p < 0.05) during enalapril treatment. Serum potassium, total lipids, high density lipoprotein cholesterol, low density lipoprotein cholesterol, glycosylated haemoglobin, serum C peptide and fructosamine levels were not significantly modified by treatment. Subjective tolerability of the drugs was also generally good. Thus, in hypertensive patients with diabetes, a diuretic free therapy based on the calcium antagonist verapamil or the ACE inhibitor enalapril, alone or combined, can effectively decrease BP without adversely affecting carbohydrate and lipid metabolism. PMID- 1283589 TI - The effect of sustained release verapamil on glucose metabolism in patients with non-insulin-dependent diabetes mellitus. PMID- 1283590 TI - Effects of treatment with verapamil SR and captopril on the lipid profile of hypertensive patients. AB - The potential beneficial effects of antihypertensive drugs on cardiovascular morbidity and mortality may be compromised by their adverse effects on serum lipid levels. In our study we compared verapamil and captopril and evaluated their effects on blood pressure and on serum lipid and lipoprotein levels, with particular attention to lipoprotein(a) [Lp(a)]. 20 hypertensive patients were treated with sustained release verapamil 240mg once daily or captopril 25mg twice daily for 3 months in a double-blind randomised study. Diastolic blood pressure was reduced from 100 +/- 3mm Hg to 87 +/- 6mm Hg (p < 0.01) and from 100 +/- 5mm Hg to 92 +/- 7mm Hg (p < 0.05) in the verapamil and captopril groups, respectively. Small but significant changes in serum lipid levels were noted: total cholesterol was reduced from 6 to 5.8 mmol/L (verapamil) and from 6.1 to 5.9 mmol/L (captopril); low density lipoprotein (LDL) cholesterol was reduced from 4 to 3.8 mmol/L (verapamil) and from 4.2 to 3.9 mmol/L (captopril); apolipoprotein C-III was reduced from 0.3 +/- 0.07 to 0.2 +/- 0.06 mmol/L (9.7 +/ 2.5 to 9.2 +/- 2.3 mg/dl) [verapamil] and from 0.2 +/- 0.1 to 0.2 +/- 0.09 mmol/L (9.1 +/- 3.7 to 8.3 +/- 3.4 mg/dl) [captopril]; apolipoprotein A-II increased only with verapamil (p < 0.02). Lp(a) levels showed only minor changes in individual patients. In conclusion, in our study verapamil and captopril were effective antihypertensive agents and did not adversely effect the lipid profile. PMID- 1283591 TI - Sodium intake does not influence the effect of verapamil in hypertensive patients with mild renal insufficiency. AB - Information is limited regarding the efficacy of antihypertensive drugs in patients with hypertension associated with renal insufficiency. To address this question, a group of 14 outpatients with essential hypertension and mild renal insufficiency received slow release verapamil 240 mg/day for 14 days after a 4 week washout period. Patients were randomly assigned to a low (4 g/day) or high (11 g/day) salt diet, and crossed over to the alternative diet after 7 days. 24 Hour blood pressure monitoring was performed at the end of the washout period and after 7 and 14 days during verapamil treatment. Verapamil induced a significant fall in mean 24-hour blood pressure that was similar for patients on both diets (p < 0.01). As expected, natriuresis increased significantly during high sodium intake (p < 0.01), and bodyweight fell significantly when sodium intake was reduced (p < 0.05). Meanwhile, serum creatinine and creatinine clearance remained stable. These results indicate that the antihypertensive effect of verapamil is independent of sodium intake even in the presence of mild renal insufficiency. PMID- 1283592 TI - Is renal protection with calcium antagonists possible? AB - Organ protection is the main goal in the treatment of high blood pressure. Consequently, this protective capacity should be one of the main characteristics of any drug used in the treatment of hypertension. A renal protective agent should protect the kidney from intrinsic renal vasoconstrictors and exogenous agents, and should also protect, or at least delay, the decline in renal function in the presence of renal insufficiency, by mechanisms other than increasing glomerular filtration pressure. Verapamil protects mesangial cells from the reduction in surface area induced by endothelin in vitro. In human subjects, it minimises the renal impairment provoked by the administration of cisplatin, and in mice it protects superficial cortical blood flow from the vasoconstriction elicited by cyclosporin. Finally, verapamil may protect from glomerulosclerosis as a result of its capacity to inhibit mesangial cell replication. PMID- 1283593 TI - Patterns of cytodistribution of prosomal antigens on the vimentin and cytokeratin networks of monkey kidney cells. AB - Prosomes were found as mRNA-associated ribonucleoprotein particles (RNP) and cofactors of untranslated (ribosome-) free mRNP. Previous data have shown the presence of prosomal networks in the cytoplasm of PtK1 and HeLa cells and their superposition onto the intermediate filaments (IF) of cytokeratin type but little if any of vimentin type. Here it is shown that in LLC-MK2 cells various prosomal antigens are present on both, vimentin and cytokeratin networks, individual prosomal antigens superposing to variable degrees onto the IF subnetworks. Some prosomal antigens in variable relative concentrations were also observed in the nuclei of these cells. We suggest the existence of prosomal subnetworks specific for each prosomal antigen superposing to a variable extent onto the IF of both types. PMID- 1283594 TI - Ventricular rhythm disturbances in the normal heart. PMID- 1283595 TI - Characterization of heterotypic adherence between transformed human lymphoblastic cells and marrow stromal cells: VCAM-1 is a ligand for one of the leukemia cell adhesion proteins. AB - Marrow stromal cells are important in normal myelopoiesis and support growth of leukemia/lymphoma (LL) cells in vitro. We have previously described the heterotypic adherence of a human B-lymphoblastic cell line (UTMB-460) to marrow stromal cells (MSC). We have extended these observations to a human T lymphoblastic cell line (CEM) and characterized the heterotypic adherence of B- and T-lymphoblastic cell lines to human MSC. Electron microscopy demonstrated UTMB-460 cells were in very close apposition to the MSC, but no specific intercellular junctions were noted. Under the conditions employed, these MSC express extracellular fibronectin, collagen types I and IV, intracellular laminin, and vimentin, but no factor VIII-R antigen. In addition, the MSC had receptors for the lectin Ulex europaeus agglutinin I. UTMB-460 and CEM cells do not adhere to extracellular matrix (ECM) proteins secreted by the MSC, i.e., fibronectin, collagen types I, III, or IV, or laminin. Monoclonal antibodies (MoAbs) against CD11a, CD11b, CD18, and CD54 and a polyclonal anti-human fibronectin antibody do not inhibit attachment of either B- or T-lymphoblastic cells to MSC. Peptides GRGES and GRGDS did not inhibit adherence of UTMB-460 and CEM cells to MSC. In contrast, the anti-vascular cell adhesion molecule (VCAM)-1 MoAb (4b9) caused significant inhibition (p < 0.01) of the adherence of both UTMB 460 and CEM cells to normal human MSC monolayers. These data suggest: (1) that MSC to which lymphoblastic cells adhere are specialized mesenchymal cells; (2) that the membrane interactions between T- and B-lymphoblastic cells and MSC involve close apposition of cell membranes of MSC and the lymphoblastic cells; (3) that the heterotypic adherence between B- and T-lymphoblastic cell lines (UTMB-460 and CEM) and MSC does not involve the RGD recognition sequence of the integrin family, the B2 leukocyte integrins, CD44, LAM-1, or the ECM proteins examined; and (4) that VCAM-1 may at least be partially responsible for heterotypic adherence between human MSC and B- and T-lymphoblastic cells. PMID- 1283596 TI - Extracellular matrix stimulation of guinea pig megakaryocyte proplatelet formation in vitro is mediated through the vitronectin receptor. AB - We have used an in vitro culture system to study the role of extracellular matrix (ECM) in the fragmentation of guinea pig bone marrow megakaryocytes (MK) and the formation of proplatelet fragments from these cells. Proplatelet formation is stimulated by culturing the cells on a hydrated type I collagen gel in the presence of serum. MK express integrin proteins alpha 5, alpha 6, beta 1, and the alpha v beta 3 complex as demonstrated by immunofluorescence. A monoclonal antibody, LM 609, to the alpha v beta 3 vitronectin receptor blocked proplatelet formation, whereas the monoclonal antibodies to the beta 1, alpha 5, and alpha 6 integrin proteins did not inhibit proplatelet formation. The tetrapeptide Arg-Gly Asp-Ser (RGDS) inhibits proplatelet formation; however, there was no inhibition by the fibronectin receptor-specific peptide GRGDdSP. The fibrinogen gamma chain peptide HHLGGAKQAGDV, which binds to the platelet membrane glycoprotein complex IIb-IIIa but not to the vitronectin receptor (VnR), did not inhibit proplatelet formation, nor did two different laminin peptides. In the absence of serum, 5.7% of MK spontaneously formed processes or fragmented. The addition of 50 micrograms/ml of vitronectin to serum-free cultures increased proplatelet formation to 21.5% of the MK, equal to cultures with 10% serum. Stimulation of proplatelet formation by vitronectin in serum-free cultures was inhibited by LM 609. Antibody staining with anti-bovine vitronectin antibody showed that MK contain intracellular vitronectin. These data show that guinea pig MK express alpha 5, alpha 6, beta 1, and alpha v beta 3 integrins. However, only the MK vitronectin receptor and its interaction with vitronectin plays an essential role in proplatelet formation in vitro. PMID- 1283597 TI - Characterization of a muscle-associated antigen from Wuchereria bancrofti. AB - A recombinant clone, WbN1, isolated from a genomic expression library of Wuchereria bancrofti and showing restricted specificity at the DNA level (Southern and PCR analyses) for Wuchereria bancrofti and Brugia malayi has been previously described. Sequence analysis of WbN1 indicated that it had notable similarity to myosin. Further characterization using in situ hybridization has localized the mRNA in the muscle of the adult parasite and in the microfilariae. Rabbit polyclonal antiserum, raised against the recombinant WbN1 fused to the maltose-binding protein, recognized a 200-kDa polypeptide in immunoblots containing B. malayi antigen extracts. The same antibody also recognized myosin extracted from Brugia pahangi, Onchocerca volvulus, and Caenorhabditis elegans. Localization using the rabbit antiserum revealed the presence of the antigen in the adult muscle tissue and in the microfilariae; the same antibody inhibited the binding of a monoclonal antibody 28.2 (directed toward MHC B of C. elegans myosin) to the recombinant WbN1 antigen and also to purified C. elegans myosin. Based on homology data, structural location, competitive ELISA, and immunoblot we conclude that WbN1 is related to myosin or a similar myofibrillar protein. PMID- 1283598 TI - E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro. AB - Endothelial cells respond to several cytokines by a rapid increase in expression of the adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM 1), followed by a gradual decline. The fate of these molecules, which was so far unknown, was studied. Specific sandwich ELISA for the detection of soluble (s)E selectin and sICAM-1 were developed. In supernatant, centrifuged 3 hr at 100,000 g to remove microparticles, from human umbilical vein endothelial cells (HUVEC) activated with tumour necrosis factor (TNF), interleukin-1 (IL-1) or lipopolysaccharide (LPS), E-selectin and ICAM-1 molecules could be detected. Biochemical analysis revealed that sE-selectin migrated as a band of approximately 94,000 MW. The amount of soluble adhesion molecules released was directly correlated with cell surface expression. Maximal release of E-selectin was observed 6-12 hr after activation of HUVEC and decreased to below detection limit 24 hr after activation. After activation, release of ICAM-1 gradually increased with ICAM-1 cell surface expression, and reached a plateau after 24 hr, which was constant for 3 days. Since E-selectin and ICAM-1 are highly expressed at inflammatory sites, the resulting high concentrations of released E-selectin and ICAM-1 may affect interactions of leucocytes with endothelial cells. The physiological role, however, of the release of E-selectin and ICAM-1 remains to be elucidated. PMID- 1283599 TI - B-T lymphocyte interactions in experimental autoimmune myasthenia gravis: autoantibody mediated up-regulation of the response of acetylcholine receptor specific T lymphocytes. AB - Twenty-six monoclonal antibodies of five different isotypes and reactive against distinct parts (alpha, beta, gamma, delta-subunits) of the nicotinic acetylcholine receptor (AChR) from Torpedo californica were screened for their capacity to enhance activation of AChR-specific CD4+ autoreactive T cells. The T cell line (LR) used in this study recognized an epitope (98-116) on the alpha subunit of Torpedo AChR. Four monoclonal antibodies bearing a gamma 2b isotype and recognizing an epitope on the Torpedo AChR alpha-subunit, especially the main immunogenic region (MIR), were able to enhance T-cell activation in a dose response manner. Four further gamma 2b isotype monoclonal antibodies, recognizing epitopes other than the AChR alpha-subunit, had no effect. Monoclonal antibodies of other isotypes (IgM, IgG1, IgG2a, IgG2c), irrespective of their subunit specificity, were unable to influence the T-cell response. Thus, the enhancement requires a IgG2b isotype, and both the antibody and the T-cell recognize an epitope on the same subunit. We have previously shown that AChR-specific B cells are directly able to present antigen to AChR-specific T-cell lines in a privileged way. The present data demonstrate that B cells are also capable of enhancing indirectly the immunogenicity of autoantigens via their humoral antibodies. PMID- 1283600 TI - Systemic lupus erythematosus murine monoclonal DNA-binding antibodies recognize cytoplasmic and nuclear phosphorylated antigens that display cell cycle redistribution in HEp-2 cells. AB - The immunological basis for the production of autoantibodies characteristic of systemic lupus erythematosus (SLE) against a wide range of antigens remains obscure. The specificity of (NZB x NZW)F1 (BWF1) or MRL/Mp-lpr/lpr (MRL/lpr) mouse monoclonal antibodies (mAb) was examined by immunofluorescence, immunoblotting and immunoprecipitation techniques. Using non-synchronized HEp-2 cells as substrate, the murine mAb were classified by indirect immunofluorescence into five groups on the basis of their staining patterns of subcellular components in interphase and mitotic stages of the cell cycle. The nature of the antigens recognized by the murine lupus was assessed by immunoblotting experiments in total, cytoplasmic and nuclear cell extracts from HEp-2 cells. The six antibodies used recognized in total cell extracts a range of polypeptides with apparent molecular weights from 25,000 to 210,000. Three polypeptides of 130,000, 110,000 and 45,000 MW were recognized by all six antibodies in both nuclear and cytoplasmic extracts. Immunoprecipitation of total cellular extracts labelled with [35S]methionine showed almost the same pattern as obtained in the immunoblotting assay. The labelling in vivo of HEp-2 cells with [32P], followed by the immunoprecipitation of the [32P]cell lysate showed that these mAb recognized phosphorylated proteins. The progressive decrease in reactivity of these mAb following treatment with higher concentrations of alkaline phosphatase in both [32P]cell lysate or nitrocellulose membranes indicates that these mAb recognize phosphorylated epitopes. PMID- 1283601 TI - The distribution of IgE plasma cells in lymphoid and non-lymphoid tissues of high IgE responder rats: differential localization of antigen-specific and 'bystander' components of the IgE response to inhaled antigen. AB - Repeated exposure of high-IgE responder rats to antigen-containing aerosols stimulates IgE responses which last for several weeks, and are eventually terminated with the onset of immunological tolerance. Studies on the distribution of total and antigen-specific IgE plasma cells and IgE mRNA during antibody production, identified the lymph nodes draining the lower respiratory tract as the primary site for initiation of the IgE response to inhaled antigen; subsequently the response seeded to mucosa-associated lymph nodes but not to central lymphoid organs. A vigorous 'bystander' IgE response (approx. x 10 the specific response) was also observed, but this was restricted to areas directly draining sites of deposition of inhaled antigen, including non-lymphoid respiratory mucosal tissues. Despite the rapid termination of the specific IgE response after the fourth week of exposure, the bystander component persisted. These results are discussed in relation to the role of cognate/non-cognate T-B interactions in the IgE response to inhaled antigens, and the relative susceptibility of each component to T-cell regulation in vivo. PMID- 1283602 TI - Diversity of anti-HLA-DR antibodies elicited by distinct anti-idiotypic monoclonal antibodies recognizing idiotopes co-expressed by the immunizing monoclonal antibody. AB - Analysis at the clonal level of the idiotypic network has identified differences in fine specificity between antigen-binding anti-anti-idiotypic (anti-anti-id) monoclonal antibody (mAb) and the original mAb as well as among antigen-binding anti-anti-idiotypic (anti-id) mAb. However, the diversity of humoral immune responses elicited by anti-id mAb recognizing idiotopes co-expressed on the immunizing mAb has not been analysed. Since this information may contribute to our understanding of the role of anti-id antibodies in the generation of diversity in the course of an immune response, we have compared the fine specificity and idiotype profile of two subsets of anti-HLA-DR mAb generated with the anti-id mAb F5-444 and F5-830. The latter mAb recognize idiotopes co expressed in the antigen-combining site of the immunizing anti-HLA-DR1,4,w14,w8,9 mAb AC1.59. These investigations showed that: (1) the two subsets of anti-HLA-DR mAb overlap only partially in their reactivity patterns with HLA-DR+ cells; (2) both subsets of anti-HLA-DR mAb recognize spatially close epitopes; (3) each subset of anti-HLA-DR mAb has unique reactivity patterns with soluble HLA-DRw16 and DRw17 antigens; and (4) each subset of anti-anti-id mAb displays a distinct idiotype profile. The subtle differences in the fine specificity and idiotype profile of the two subsets of anti-HLA-DR mAb suggest that anti-id antibodies may play a role in the generation of diversity in the course of a humoral immune response. PMID- 1283603 TI - Identification of an immunodominant B-cell epitope in bovine type II collagen and the production of antibodies to type II collagen by immunization with a synthetic peptide representing this epitope. AB - Using epitope scanning of 272 short, synthetic peptides representing the amino acid sequence of the CB-11 peptide of type II collagen, we have shown that five strains of rat, immunized with type II collagen, produce antibodies to a region 37-45 amino acids from the amino end of CB-11 peptide. Antibodies to this region always gave the highest binding values suggesting that it is an immunodominant region. Wistar rats immunized with a synthetic peptide representing this region, coupled to keyhole limpet haemocyanin, produced antibodies to this peptide which could still be detected at 1:4000 to 1:8000 dilution but none developed clinical arthritis. All sera also showed binding of antibodies to denatured bovine type II collagen but not to native type II collagen, keyhole limpet haemocyanin or to bovine serum albumin by ELISA. Sera from peptide-immunized rats were examined for antibody binding to the 272 short peptides of the CB-11 peptide and to the synthetic peptides representing shortened forms of the immunodominant region and forms of it with substituted amino acids. These results showed that the antibodies in the peptide-immunized rats were not identical to those produced to that peptide by rats immunized with type II collagen but may represent subpopulations of them. These findings suggest caution in interpreting the role of antibodies to individual peptides in arthritis induction without knowledge of their fine specificity. PMID- 1283604 TI - The use of GM-CSF in AIDS. AB - Hematopoietic growth factors may mitigate the cytopenias that frequently complicate HIV disease or its treatment. Clinical and in vitro studies have indicated the ability of granulocyte-macrophage colony-stimulating factor (GM CSF), granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) to overcome the myelosuppression of HIV or many of the drug therapies used in the care of HIV-infected individuals. In addition, neutrophil or monocyte functional abnormalities observed in AIDS patients may be improved by the use of GM-CSF. Issues which may distinguish the use of hematopoietic growth factors in AIDS as compared with in other clinical settings include: 1) interaction of the growth factor with other cytokines which are aberrantly expressed, 2) direct effects of the growth factor on the replicative activity of HIV, and 3) potential interactions of the growth factor with other concurrently administered medications. This review focuses on the potential roles and limitations of growth factor use in AIDS and reviews the clinical studies using GM-CSF in HIV-infected individuals. PMID- 1283605 TI - Induction of neointima formation by platelet derived angiogenesis fraction in a small diameter, wide pore, PTFE graft. AB - Enhancement of endothelialization and patency of a small diameter (2 mm), wide pore, PTFE graft was attempted by coating the luminal surface with a platelet derived angiogenesis fraction (PDAF) and implanting it in a rat model. PDAF was delivered to the grafts by combining it with a carrier polymer. PDAF-treated grafts were initially implanted in the retroperitoneum for 21 days followed by removal of one for histology and in situ end to side bypass to the infrarenal aorta for the other. Vascularized grafts were examined at 14 days for patency and 100 days for patency and histology. Significant differences were noted in transmural ingrowth of capillaries and tissue at 21 days post implantation in PDAF-treated versus untreated grafts. Similarly, near significance was noted in capillary ingrowth and significance was noted in tissue ingrowth at 100 days in PDAF-treated grafts. Despite favorable trends particularly early in the time course, no significant differences in graft patency, endothelialization, or hydroxyproline content was demonstrated between PDAF-treated and untreated grafts. Results of this preliminary study are encouraging for further study of PDAF-treated PTFE grafts and the potential that rapid vascularized neointima formation results improved in graft patency rates. PMID- 1283606 TI - Post-antibiotic effect of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin for Pseudomonas cepacia. AB - The post-antibiotic effects (PAE) of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin were studied for ten strains of Pseudomonas cepacia isolated from patients with cystic fibrosis. Antibiotic concentrations used for exposure were either the MIC of each agent for the sensitive isolates or the recommended sensitivity breakpoint concentrations for the resistant isolates. After 2 h of exposure, cultures were rapidly diluted 1000-fold to eliminate the antibiotic. Out of the ten isolates, there were eight sensitive to ceftazidime, six to ciprofloxacin, six to imipenem, nine to piperacillin and five to tobramycin. All antibiotics tested demonstrated PAE for some isolates of P. cepacia, however, each antibiotic failed to produce a PAE for at least one isolate. The mean PAE was 1.35 h for ceftazidime, 2.38 h for ciprofloxacin, 2.39 h for imipenem, 2.16 h for piperacillin and 1.77 h for tobramycin. Imipenem demonstrated PAE of > or = 0.5 h for all sensitive isolates tested; ceftazidime, piperacillin, ciprofloxacin and tobramycin demonstrated PAE of > or = 0.5 h for 6/8, 8/9, 5/6 and 2/5 sensitive isolates, respectively. These data indicate that several antibiotics have significant (> or = 0.5 h) PAE for isolates of P. cepacia. PMID- 1283607 TI - Investigation of the role of Von Korff fibers during murine dentinogenesis. AB - The existence and significance of Von Korff fibers during early dentinogenesis are still very controversial. The purpose of the present study was to re-examine the questions of the existence, nature and significance of Von Korff's fibers using light microscopy and immunohistochemistry. Specimens were obtained from 3 days-old CD-I mice and mandibles were carefully dissected under constant irrigation and immediately fixed in 10% neutral buffered formalin for light microscopy. Sections were treated or not with collagenase prior to silver staining. For immunohistochemistry, specimens were fixed in 95% ethanol and embedded in paraffin. Sections were reacted with goat anti-human-bovine type I or type III collagen and a rhodamine (RITC) labelled rabbit anti-goat IgG was then reacted as a secondary antibody. Slides were then examined under a Zeiss II photomicroscope equipped with epifluorescence. Our results have confirmed the presence of argyrophilic material concentrated at the periphery of the dental papilla and stretching from the subodontoblastic layer to the future dentino enamel junction. The distribution of type III collagen was very similar to the distribution of the silver staining at the cervical loop area. Type I collagen distribution was different and concentrated in areas where odontoblasts were fully differentiated. Our study showed that Von Korff fibers are not artefactual. We have established the presence of an apical compartment containing type I collagen fibers and a basal compartment containing type III collagen to explain the image of continuous silver staining crossing the entire thickness of the odontoblast layer. PMID- 1283608 TI - Langerhans cell dynamics in human gingiva during experimentally induced inflammation. AB - The changes in the number of Langerhans cells within the gingiva during a 21 day experimental gingivitis episode were investigated immunohistochemically. Monoclonal antibodies to CD1a (specific for Langerhans cells and thymocytes) and HLA-DR (class II major histocompatibility antigens - (MHC)) were used to identify Langerhans cells within gingival biopsies taken on days 0, 7, 14 and 21. HLA-DR antibody stained dendritic cells within the oral epithelium which were morphologically identical to the CD1a+ Langerhans cells. Class II MHC LC numbers rose and plateaued between day 7 and 14 then decreased to baseline by day 21. As plaque accumulated and initial inflammation developed there was an increase in the number of CD1a+ Langerhans cells which peaked at day 7 and stayed high (day 14). As inflammation developed there was a statistically significant decrease in the number of CD1a+ Langerhans cells by day 21 (p = 0.028). The initial increase, followed by a decrease in CD1a+ Langerhans cells as inflammation developed, suggests that migration of Langerhans cells occurs within the gingival epithelium and this may represent an important early event in the gingival immune response to plaque. PMID- 1283609 TI - Effects of culture passages on collagen immunostaining in human dental pulp and gingival fibroblasts. AB - In this study, a scanning microscopic computer-assisted image analysis system was used for the immunocytochemical characterisation of collagen types I, III and V in normal human fibroblasts from pulp and gingival explants, using specific purified antibodies and peroxidase labeling. The culture conditions were standardized in order to evaluate simultaneously the expression of the three antigens in four different culture passages of the two fibroblast types. The optical density values of immunostaining intensities were quantified, the integrated optical density per cell was calculated, and the results were analyzed by a variance test. It was found that all three collagen types were present in the tissues, and in both gingival and pulp fibroblasts after three to nine culture passages. A non-parametric statistical analysis of the staining intensity variances revealed significant differences between antigenic levels depending on the tissue origin of the fibroblasts and an effect of culture passages. The results seemed to justify application of this technique at the light microscope level for the evaluation of collagen production, the principal function of fibroblasts, but the tissue origin and number of culture passages should be taken into consideration for in vitro biocompatibility testing of dental materials. PMID- 1283610 TI - Projections to the inferior colliculus from the dorsal column nuclei. An experimental electron microscopic study in the cat. AB - The projections from the dorsal column nuclei (DCN) to the inferior colliculus (IC) were investigated in cats by means of electron microscopy. The DCN were destroyed unilaterally by electrocoagulation and the animals survived 3 or 4 days. A variable number of degenerating synaptic boutons were observed bilaterally in the IC-external nucleus and in the intercollicular area. The greatest number of degenerating terminals was encountered in the rostral portions of the IC-external nucleus and in the intercollicular area contralateral to the DCN lesion. In these regions some series of ultrathin sections the degenerating boutons comprised 6-13% of the entire synaptic bouton population of the examined area. In the caudal portion of the contralateral IC-external nucleus the number of degenerating boutons greatly diminished and the latter showed a patchy distribution. Ipsilateral to the DCN lesion the number of degenerating terminals was low, and a more substantial number was found only in the rostroventral portion of the IC-external nucleus and in the intercollicular area. The degenerating synaptic boutons displayed markedly diverse patterns of alterations. Most often was the dark (electron-dense) degeneration pattern, followed by the filamentous degeneration. More rare were the light (electron-lucent) degenerating boutons, and a very limited number of terminals displayed pinocytotic degeneration changes. The DCN boutons contained round and oval synaptic vesicles and terminated mainly on proximal dendritic trunks, followed by the perikarya of the efferent neurons, and smaller, distal dendrites. Rarely the degenerating terminals contacted dendritic spines, and no contacts were found with the small (interneuronal) perikarya and with other vesicle containing profiles. The axodendritic contacts were asymmetrical and the axosomatic--from the intermediate type. In agreement with previous light microscopic data, the present findings demonstrate the existence of substantial excitatory projection from the DCN to the polysensory nuclei of the IC that integrate converging auditory and tactile information, and are involved in acoustico-motor behavior. PMID- 1283611 TI - Symbolic play development in toddlers with expressive specific language impairment (SLI-E). AB - Twenty toddlers with expressive specific language impairment (SLI-E) and 20 toddlers with normal language development were compared in their symbolic play development. The groups did not differ in amount of engagement with the toys or in functional conventional play behaviors. However, the children with SLI-E displayed less decentered play (use of play schemes with a doll or another person), less well-developed sequential play, and fewer occurrences of symbolic play transformations (use of a neutral object or an absent object to carry out pretending). The provision of structure in the form of thematically related toy sets, instructions, and modeling did not reduce the discrepancy between demonstrated play behaviors of toddlers with SLI-E and their normally developing peers. Three possible explanations for this discrepancy are considered: a "stylistic" difference in play, a developmental lag in symbol use, or a deficit in retrieval of stored symbolic representation. PMID- 1283612 TI - Spoken and written language relationships in language/learning-impaired and normally achieving school-age children. AB - Students with language/learning impairment (LLI) and three groups of normally achieving children matched for chronological age, spoken language, and reading abilities wrote and told stories that were analyzed according to a three dimensional language analysis system. Spoken narratives were linguistically superior to written narratives in many respects. The content of written narratives, however, was organized differently than the content of spoken narratives. Spoken narratives contained more local interconnections than global interconnections; the opposite was true for written narratives. LLI and reading matched children evidenced speaking-writing relationships that differed from those of the age- and language-matched children in the way language form was organized. Further, LLI children produced more grammatically unacceptable complex T-units in their spoken and written stories than students from any of the three matched groups. The discussion focuses on mechanisms underlying the development of speaking-writing differences and ramifications of spoken-language impairment for spoken and written-language relationships. PMID- 1283613 TI - Contextual and linguistic correlates of intelligibility in children with developmental phonological disorders. AB - Listeners' glosses of children's intended words provided data for two studies of the potential influence of selected contextual and linguistic variables on word intelligibility. Several regularities associated with the occurrence of unintelligible words were identified. In Study I, intelligibility outcomes were associated with utterance length and fluency, word position, intelligibility of adjacent words, phonological complexity, and grammatical form. In Study II, intelligibility outcomes were associated with phonological complexity, syllabic structure, and grammatical form. Discussion considers the implications of these and other regularities associated with the occurrence of unintelligible words for a comprehensive perspective on the utterance-to-utterance intelligibility deficits of children with phonological disorders of unknown origin. PMID- 1283614 TI - Symbol vocabulary and the focus of conversations: augmenting language development for youth with mental retardation. AB - Communication devices designed to augment the language development of individuals with severe cognitive disabilities and little or no functional speech typically contain primarily nouns because they seem easiest to acquire and evaluate. In this study, the effect of a more diverse vocabulary was assessed. Systematic observations of the use of computerized speech-output devices by 12 youth with moderate or severe mental retardation and severe spoken language disability and by their partners were made over a 2-year period. Social-regulative symbols (e.g., "please," "I'm finished") were used as soon as they were introduced, and their availability expanded the focus of conversations both at home and at school. Implications for conceptualizing variation in early language use and for the design of language intervention programs are discussed. PMID- 1283615 TI - Effects of configuration on the paired-associate learning of blissymbols by preschool children with normal cognitive abilities. AB - Translucency appears to be a potent variable in the learning of Blissymbols by preschool children with normal cognitive abilities. Complexity does not appear to influence learning for these individuals when there is a concurrent condition of high translucency. However, a condition of high complexity seems to enhance the learnability of Blissmbols having low translucency. For the present experiment, an attempt was made to determine if symbol configuration affects the learning of highly complex Blissymbols that bear little relationship to their referents. A paired-associate learning paradigm was used to present 30 Blissymbols to 20 cognitively normal preschool children. These symbols were evenly divided into superimposed and nonsuperimposed groups. Results indicated that the children learned more superimposed symbols than their nonsuperimposed counterparts. The implications of this finding for the teaching of Blissymbols are discussed. PMID- 1283616 TI - Interactions of lithium with the adrenergic system in electrically-stimulated guinea pig myenteric plexus isolated preparations. Actions of a phosphodiesterase inhibitor. AB - The possible involvement of lithium in the mechanism of action of norepinephrine has been studied in electrically-stimulated preparations isolated from guinea pig myenteric plexus. Results show that concentrations of lithium above 0.5 x 10(-2) M significantly inhibit the norepinephrine effect. The results obtained when preparations were preincubated with alpha-adrenergic blocking agents (phenoxybenzamine and phentolamine) suggest a beta-adrenergic action of lithium since these substances induced 74% and 37% inhibition of the lithium effects, respectively. When preparations were preincubated with beta-adrenergic blocking agents (propranolol, toliprolol, atenolol and sotalol) the action of lithium was unchanged. A phosphodiesterase inhibitor also led to 50% inhibition of the lithium effects. These results, together with the fact that the adenylate cyclase cAMP system is linked directly to the beta-adrenoceptors, suggest that the inhibitory action of lithium on norepinephrine, in this preparation, is related to its beta-adrenergic action, which agrees with the results obtained in brain by other authors. PMID- 1283617 TI - The effect of hypoxia on brain edema--the promoting effect of superimposed hypercapnia or hypertension. AB - The effects of hypoxia and superimposed hypercapnia or hypertension during hypoxia on brain tissue water content, pH, and electric activity were studied in Sprague-Dawley and stroke-prone spontaneously hypertensive rats. Auditory brainstem responses and sensory evoked potentials were recorded during the experiment as the indices for cerebral oxygen metabolism. The brains were removed immediately, 1 day, and 2 days after hypoxic insult for gravimetric study. The brain water content increased in all groups on the 1st and 2nd days after hypoxia. The percentage change from the control water content increased only on the 1st day in hypoxic rats. In contrast, it increased on both the 1st and 2nd days after hypoxia in hypercapnic or hypertensive rats. The evoked potentials of hypoxic and hypercapnic-hypoxic rats showed that peak latencies were prolonged significantly during hypoxia and recovered 1 and 2 days after hypoxia. The brain tissue pH decreased during hypoxia and recovered after hypoxia. This study suggests that brain edema develops within 2 days of hypoxic insult and that superimposed hypercapnia or hypertension promotes the brain edema. PMID- 1283618 TI - Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma. AB - Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-beta, 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3 nitroso ure a hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-beta intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas. PMID- 1283619 TI - Prognostic factors in patients surviving for more than 1 or 5 years after removal of metastatic brain tumors. AB - Favorable and unfavorable prognostic factors were identified in 28 patients surviving for more than 1 year after surgery for metastatic brain tumor and 18 patients surviving for more than 5 years. A high incidence of favorable factors, including neurological grade and location of the brain lesion, indicated significance in the prognosis. A low incidence of favorable factors, including tumor-free interval and presence or absence of extracranial tumor, indicated little significance to the prognosis. PMID- 1283620 TI - Suprachiasmal carotid-ophthalmic artery aneurysm--report of two cases. AB - Two rare suprachiasmal carotid-ophthalmic artery aneurysms, one large and one giant, were discovered incidentally. The patients had no visual disturbances. Angiography showed superomedial projection of the sac. The aneurysms were clipped via an ipsilateral pterional approach. A suprachiasmal carotid-ophthalmic artery aneurysm is indicated when preoperative angiography reveals a superomedial carotid-ophthalmic artery aneurysm without visual disturbances. Direct surgery to clipp a suprachiasmal aneurysm should be carried out to prevent rupture of these frequently large aneurysms. PMID- 1283621 TI - Subfrontal schwannoma--case report. AB - A rare case of subfrontal schwannoma occurred in a 33-year-old male with the chief complaint of headache. Computed tomography demonstrated a low-density mass in the subfrontal region. Magnetic resonance imaging indicated the mass extension into the ethmoidal sinus. The tumor was totally removed via a subfrontal approach. The histological diagnosis was schwannoma. The most likely origin of the tumor is the meningeal branches or anterior ethmoidal nerve. PMID- 1283622 TI - Abnormal continuous flow in giant intracranial aneurysm detected by transcranial Doppler sonography--case report. AB - Transcranial Doppler sonography demonstrated a huge, non-thrombosed intracranial aneurysm in a 62-year-old male preoperatively as abnormal continuous flow, which disappeared after aneurysmal neck clipping. Transcranial Doppler sonography is very useful to assess hemodynamics in the parent artery and the dome of the aneurysm. PMID- 1283623 TI - Aneurysm of the cervical internal carotid artery associated with Marfan's syndrome--case report. AB - An aneurysm of the internal carotid artery associated with Marfan's syndrome occurred in a 23-year-old female with a 2-year history of a pulsating lesion in the left neck, which progressively increased in size. Left carotid angiography demonstrated a giant saccular aneurysm at the origin of the internal carotid artery. The aneurysm was excised and end-to-end anastomosis performed without postoperative morbidity. PMID- 1283624 TI - Contralateral development of acute subdural hematoma following surgery for chronic subdural hematoma--case report. AB - An unusual case of acute subdural hematoma developed after drainage of chronic subdural hematoma in a 71-year-old male. The acute subdural hematoma was located over a membranous layer in the subdural space similar to the outer membrane of the chronic subdural hematoma. Intraoperatively, bleeding from the bridging vein and oozing from the superior sagittal sinus were observed. The membranous layer probably separated from the dura mater following decompression after drainage of the contralateral hematoma, and this separation then damaged the bridging vein and superior sagittal sinus, resulting in the acute subdural hematoma. PMID- 1283625 TI - Papillary craniopharyngioma of the third ventricle--case report. AB - A papillary craniopharyngioma localized in the third ventricle occurred in a 45 year-old male. The clinical presentation was unusual and the neuroradiological appearance resembled a choroid plexus papilloma of the third ventricle. The tumor originated from the right anterolateral wall of the third ventricle, forming a discrete mass with prominent papillae formation. The tumor was totally removed by a transcallosal approach without neurological or endocrinological sequelae. PMID- 1283626 TI - Malignant fibrous histiocytoma in the skull--case report. AB - A 45-year-old male presented with a large calvarial mass caused by a malignant fibrous histiocytoma arising primarily from the frontal bone and extending into the intracranial space. Magnetic resonance imaging revealed a well-demarcated, mottled enhanced bulky tumor with several low-signal separations. He underwent extensive tumor and bone removal, followed by radiation therapy. Histological examination showed pleomorphic spindle cells in a storiform pattern. The tissue stained positive for alpha-1-antitrypsin and alpha-1-antichymotrypsin by immunohistochemical techniques. PMID- 1283627 TI - Variant forms of galanin isolated from porcine brain. AB - In a peptide concentrate, prepared from acid extracts of porcine brain, several galanin-like immunoreactive peptides were detected and two of these were purified. Characterization of the peptides by sequence analysis, mass spectrometry, and capillary zone electrophoresis identified them as a N terminally nine residue elongated form of galanin, preprogalanin(24-61) amide, and as an N-terminally four residue truncated form of galanin corresponding to preprogalanin(37-61) amide. The former finding suggests that the removal of the signal peptide in preprogalanin occurs by enzymatic cleavage between glycine-23 and leucine-24. The presence of truncated galanin might refer to a mechanism, where galanin is inactivated by removal of functionally important amino acid residues from the N-terminus. PMID- 1283628 TI - Orofacial pain increases mRNA level for galanin in the trigeminal nucleus caudalis of the rat. AB - The changes of preprogalanin mRNA levels in the superficial dorsal horn neurons (laminae I and II) of the trigeminal nucleus caudalis in response to orofacial pain induced by the injection of 5% formalin into the lips of rats was investigated and compared to those of preproenkephalin A mRNA and preprodynorphin mRNA in the same region by means of in situ hybridization histochemistry. Rapid and marked increases of preprogalanin and preprodynorphin mRNA were observed on the side of the injection, but the increase of preproenkephalin A mRNA level was less pronounced than that of the other two mRNAs, indicating that these peptides have different roles in the dorsal horn analgesic mechanism and that galanin, in addition to opioid peptides, may have a highly specific role in this mechanism. PMID- 1283629 TI - Circulating neuropeptide Y in dog plasma consists of multiple peptide fragments. AB - Neuropeptide Y-like immunoreactivity (NPY-LI) in dog plasma was characterized and quantified using three extraction methods (Sep-Pak:acetonitrile, HCl:ethanol, and ethanol). Sep-Pak extraction yields the best recovery and preserves the integrity of the peptide. Oxidized NPY is not generated during blood collection. Using two antisera of different specificities, at least three peptide forms in normal dog arterial and venous plasma were detected. A peptide with retention times similar to oxidized NPY or peptide YY is the major component of plasma NPY-LI under basal conditions, but NPY(1-36) predominates during sympathetic stimulation. The mature peptide in dog plasma is similar to human NPY. The antiserum ABII provides a more accurate measure of circulating NPY(1-36) and its oxidized form. The antiserum ABI is useful for detecting NPY-like fragments. PMID- 1283630 TI - Selective labeling of alpha- or epsilon-amino groups in peptides by the Bolton Hunter reagent. AB - Incorporation of N-succinimidyl-3(4-hydroxyphenyl) propionate (Bolton-Hunter reagent) or its 125I-labeled derivative into peptides can be selectively directed towards either alpha- or epsilon-amine functions by modifying the pH of the reaction. Acylation of alpha-amino groups is favored at pH 6.5 whereas epsilon amino groups react more readily at pH 8.5. We have taken advantage of this result to prepare two new 125I-labeled analogues of substance P and neurotensin that bind selectively and reversibly to their respective receptors. The method described here is of general interest and can be used to incorporate various reporter groups into peptide structures. PMID- 1283631 TI - Regulation of galanin secretion from pituitary cells in vitro by estradiol and GHRH. AB - The effects of estradiol and growth hormone-releasing hormone (GHRH) on galanin release from anterior pituitary cells were examined in vitro. 17-beta-Estradiol (0.001-10 nM) increased galanin secretion from anterior pituitary cells in a concentration-dependent manner. Estradiol (10 nM) increased galanin release 300 and 600% from pituitary cells of ovariectomized and male rats, respectively. Immunocytochemical studies demonstrated that estradiol (10 nM) increased the number of galanin-containing cells twofold after 4 days in culture. Growth hormone-releasing hormone (1 and 10 nM) increased and SRIF (1 and 10 nM) decreased galanin release from pituitary cells of ovariectomized and male rats. We conclude that estradiol increases galanin release by a direct effect on pituitary cells, in part by increasing the number of pituitary cells synthesizing galanin. In addition, GHRH stimulates galanin release when estradiol levels are low. PMID- 1283632 TI - The role of rigid oesophagoscopy in oesophageal carcinoma. AB - The efficacy and safety of rigid oesophagoscopy in diagnostic and therapeutic settings in a consecutive series of 404 patients with oesophageal carcinoma were studied and compared to that for flexible oesophagoscopy in the same group. In addition, we examined the same parameters in a smaller group who had undergone radiotherapy with subsequent malignant stricturing. We performed 328 rigid procedures and 118 flexible procedures in a single regional surgical referral unit over a 7 year period. The combined perforation rate was 1.3%, with an overall mortality of 1% from 446 procedures. We conclude that rigid oesophagoscopy in the presence of carcinoma retains an important diagnostic and therapeutic role which can be achieved with low incidence of perforation in high risk patients. PMID- 1283633 TI - Prenatal diagnosis of spina bifida aperta after first-trimester valproate exposure. AB - In the context of a prospective study on the adverse effects of anti-epileptic drugs on fetal outcome, we evaluated our experience with prenatal diagnosis by ultrasonography and alpha-fetoprotein (AFP) determination in amniotic fluid. We compared these results with AFP values in maternal serum obtained prior to amniocentesis. From November 1985 to July 1990, amniocentesis at 16-18 weeks of gestation was performed in 267 pregnancies of 237 different women using anti epileptic drugs. Among 92 pregnancies with maternal valproic acid use, five (including one concordantly affected monozygotic twin-pair) were terminated because of a spina bifida aperta, all prenatally diagnosed by AFP determination and acetylcholinesterase electrophoresis in amniotic fluid. The maternal serum AFP level was raised (> or = 2.5 multiples of the median (MOM) for singleton pregnancies and > or = 4.5 MOM for twin pregnancies) in only two of these five affected pregnancies. We emphasize that maternal serum AFP levels may be unreliable for prenatal screening for fetal neural tube defects in women taking valproate and recommend that amniocentesis and fetal ultrasound examination should be offered directly. PMID- 1283634 TI - Prospective intervention trial of a screening protocol to identify fetal trisomy 18 using maternal serum alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin. AB - Two prenatal centres in New England, routinely using a screening protocol for fetal Down syndrome that included maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG) measurements in combination with maternal age, adopted a separate screening protocol for trisomy 18. That protocol identified a pregnancy as being at high risk when AFP, uE3, and hCG measurements all fell at or below specified cut-offs (0.75, 0.60, and 0.55 multiples of the median, respectively), regardless of maternal age. Among the first 19,491 women screened, 98 (0.5 per cent) were found to have values which placed them in the high-risk category. Four of these women were subsequently found not to be pregnant. In two others, samples from non-pregnant individuals were found to have been incorrectly submitted for analysis in place of the samples from the pregnant women. All of the remaining 92 women were counselled and offered amniocentesis and fetal karyotyping. Eighty-eight (96 per cent) accepted. Karyotypes or birth outcomes were available on all 92 pregnancies. Six cases of trisomy 18 and one case of Turner syndrome were identified by karyotype. One case of trisomy 18 was identified for every 14 unaffected pregnancies offered amniocentesis. In the present prospective study, an estimated 85 per cent of the cases of trisomy 18 were identified. However, given the small number of cases (six), the 95 per cent confidence interval for the detection rate is broad (40-95 per cent). PMID- 1283635 TI - Synaptic connections of physiologically identified geniculocortical axons in kitten cortical area 17. AB - Single geniculocortical axons were recorded in the cortical white matter of kittens and adult cats by using micropipettes filled with horseradish peroxidase (HRP). Of 41 axons recovered in 4-5 week old kittens, three well-filled axons arborized in area 17; the remainder were incomplete or arborized in area 18. One axon had Y-like physiological properties, two were X-like. They were recovered from two 34-day-old kittens. All three axons formed clustered arborizations, mainly in layer 4A. Electron microscopic (EM) analysis of 50 boutons from kitten and 38 boutons from adult controls revealed that the boutons from kitten made synapses more frequently on spines (91% of targets) than did the boutons from the adult (71%). One X-like axon in kitten also had a collateral projection that made synapses in layer 1; this has not been seen in adult cats. In overall extent, the axons from kitten fell within the adult range. PMID- 1283636 TI - Reciprocal role of the inward currents ib, Na and i(f) in controlling and stabilizing pacemaker frequency of rabbit sino-atrial node cells. AB - Experiments and computations were done to clarify the role of the various inward currents in generating and modulating pacemaker frequency. Ionic currents in rabbit single isolated sino-atrial (SA) node cells were measured using the nystatin-permeabilized patch-clamp technique. The results were used to refine the Noble-DiFrancesco-Denyer model of spontaneous pacemaker activity of the SA node. This model was then used to show that the pacemaker frequency is relatively insensitive to the magnitude of the sodium-dependent inward background current ib, Na. This is because reducing ib, Na hyperpolarizes the cell and so activates more hyperpolarizing-activated current, i(f), whereas the converse occurs when ib, Na is increased. The result is that i(f) and ib, Na replace one another and so stabilize nodal pacemaker frequency. PMID- 1283637 TI - Different channel-gating properties of two classes of cyclic GMP-activated channel in vertebrate photoreceptors. AB - We report that two types of cGMP-activated channel coexist in the photoreceptor plasma membrane, with the most commonly encountered class appearing broadly similar to the channel reported in previous patch-pipette experiments. However, we find that flickering of this channel between the open and closed states is so rapid that a discrete single-channel conductance cannot unequivocally be resolved; the occurrence of flickering is largely independent of membrane voltage and of the presence of cytoplasmic Ca2+ or Mg2+. In recordings from the inner segment we occasionally find a second class of cGMP-gated channel, with activity resembling that reported for cloned channels. This channel does not flicker, but instead exhibits distinct open-close transitions. Our results suggest that the predominant form of channel in vivo differs significantly from cloned channels, and that its gating properties are not as simple as reported previously. PMID- 1283638 TI - Poisson sampling-based inference for single ion channel data with time interval omission. AB - Patch-clamp recording allows investigations of the gating kinetics of single ion channels. Statistical analysis of kinetic data can enhance our understanding of channel gating at a molecular level. Experimental channel records suffer from time interval omission, i.e. failure to detect brief channel openings and closings. It is important to incorporate this phenomenon into statistical analyses of ion channel data. When time interval omission is ignored, the method of maximum likelihood can usually be used to estimate gating parameters from a single channel record. However, it is far more difficult to apply this method when time interval omission is incorporated. We present an alternative approach to parameter estimation based on Poisson sampling. A simulated homogeneous Poisson process is superimposed onto the channel record and inference is based on the numbers of points in successive open and closed sojourns, rather than on the sojourn times themselves. We describe the method for the two-state Markov model C<-->O, although it is applicable to more general models. Computer-simulated data are used to demonstrate the efficacy of the method. Modifications of the method are discussed briefly. PMID- 1283639 TI - Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. AB - To cast light on the subunit composition of native NMDA-type glutamate receptors, four cloned subunits of the NMDA receptor have been expressed, in pairs, in Xenopus oocytes, and their single-channel properties have been measured. The conductances of the channels, and their characteristic patterns of sublevel transitions, turn out to be useful diagnostic criteria for subunit composition. The NR1-NR2A and NR1-NR2B combinations (which have identical TM2 sequences) are very similar to each other. Both have 50 pS openings and brief 40 pS sublevels (in 1 mM external Ca2+), with similar mean lifetimes and frequencies. They also show close quantitative resemblance to the channels of hippocampal CA1 and dentate gyrus cells and of cerebellar granule cells, except that the NR1-NR2A combination has a lower glycine sensitivity than the native channels. In contrast, the NR1-NR2C combination produces a channel with 36 pS and 19 pS conductances of similar (brief) duration; these closely resemble the 38-18 pS channels that have previously been observed in large cerebellar neurons in culture (together with 50 pS channels). PMID- 1283640 TI - Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. AB - The NMDA class of glutamate receptors have the unique property of binding some agonists, including glutamate, for a very long period of time. One manifestation of this is that brief (1 ms) application of glutamate (1 mM) produces a slowly decaying current, the major component of which has a time constant of approximately 200 ms. Application of glutamate at low concentrations allows identification of groups ('superclusters') of openings in the data record that probably correspond to a single period during which one or more molecules of glutamate are bound to the receptor, i.e. a single activation of the channel. The length of such superclusters is long on average (74 ms); the longest component of the distribution has a duration of approximately 300 ms, and comprises about 25% of the area. However, aligning many superclusters to obtain an average current reveals that the decay is mainly fast; the major component has a time constant of around only 5 ms. It is shown that incorporation of a distribution of first latencies (from the time of the jump to the first opening) can explain at least part of this discrepancy. PMID- 1283641 TI - A combination of human alpha 1 and beta 1 subunits is required for formation of detectable GABA-activated chloride channels in Sf9 cells. AB - The baculovirus expression system was used to produce alpha 1 and beta 1 subunits of the human GABAA receptor in Sf9 cells. In cells infected with both alpha 1 and beta 1 recombinant viruses, GABA elicited an outwardly rectifying chloride current that was blocked by bicuculline and potentiated by pentobarbitone. GABA did not produce detectable currents in cells infected with either alpha 1 or beta 1 recombinant viruses alone. In these cells, and in control (non-infected) Sf9 cells, pentobarbitone depressed the leakage current (Ki = 55 microM). Fluorescently labelled monoclonal antibodies to the alpha 1 subunit showed greater amounts of the alpha 1 subunit in cells infected with only the alpha 1 recombinant virus than in cells co-infected with the alpha 1 and beta 1 recombinant viruses. Fluorescence of the plasma membrane was seen in cells co infected with the alpha 1 and beta 1 recombinant viruses, but was absent in cells infected with only the alpha 1 recombinant virus. It was concluded that the alpha 1 subunit normally interacts with the beta 1 subunit to be transported to the plasma membrane in Sf9 cells. PMID- 1283642 TI - [The autistic child, his thoughts, his body and his images. Or the footprint of a step not yet taken]. AB - The author studies the autistic mind through the concept of image. This concept is differentiated from the processes of representing (and mainly self representation), figuration and communication. The author then discusses different aspects of the image: mental image, mirror image and physical image. Finally is discussed the narcissistic or objectal polarity of image production in the autistic child and the author argues that in these cases the transformation from the original to the primary level is essentially disturbed. PMID- 1283643 TI - Biochemical and morphological alterations in the lungs and livers of mice following exposure to polluted air in a traffic tunnel. AB - The air in the Lin-Shen tunnel in Taipei is heavily polluted due to heavy traffic. To elucidate the biologic effects of air pollution, we studied the biochemical alterations of Polycyclic aromatic hydrocarbons metabolic enzymes and histological changes in the livers and lungs in experimental mice under long-term and short-term exposure to the tunnel air. The concentrations of 16 Polycyclic aromatic hydrocarbons in the air were measured by HPLC, and the mutagenicity of the extract of air particulates was assayed by the Ames test. We found that the benzo(a)pyrene hydroxylase and cytochrome P-450 in the livers and nitroreductase in the lungs of the 30-day exposed animals were significantly increased as compared to the unexposed control (p < 0.005). The nitroreductase in the liver also increased but not significantly. The lungs of long-term (6 mo.) exposed mice showed anthracosis, chronic inflammation, and emphysema (10/10). The livers of the experimental animals did not show significant alteration. A whitish circular nodule appeared on the liver surface of one mouse (1/10). Microscopically, the nodule showed necrosis and hyperchromatic cells around the central vein. It is concluded that the polluted air in the traffic tunnel has evident biohazardous effects on the lungs and livers of mice under the experimental conditions. PMID- 1283644 TI - [Benign prostatic hypertrophy: the therapeutic options]. AB - BPH is a very diffuse condition among males increasing in incidence with the age. This explains the large interest in the evaluation of the different strategies concerning BPH treatment. The gold standard has still to be considered the transurethral resection of the prostate which all the other treatments must be compared to. More recently as alternatives to the invasive therapy, so called minimally invasive treatments have been proposed (thermotherapy, prostate dilatation, intraprostatic stents) whose real significance is not completely evaluable yet. As far as medical treatment is concerned, phyto-therapeutic agents have been partially replaced by different substances (alfa- blockers; 5-alfa reductase blockers) that are expected to have a promising future. PMID- 1283645 TI - Endothelin, vasopressin, and substance P like immunoreactivity in cultured and intact epithelium from rabbit trachea. AB - BACKGROUND: The control of airways reactivity is essential to our understanding of disease processes such as asthma. Many studies have examined the neural control of the airways, but more recently there has been evidence to show that the epithelium lining the airways may influence airways reactivity. METHODS: Rabbit tracheal epithelial cells were dispersed with enzymes, grown in primary culture and fixed. Tissue from intact tracheas was also sampled and fixed. Localisation of the vasoactive substances endothelin-1, arginine-vasopressin, and substance P was investigated by immunolabelling techniques. RESULTS: Scattered immunolabelling to endothelin-1, arginine-vasopressin, and substance P was found throughout the cultures (with < 20% of cells staining positively to each antibody). At the ultrastructural level this immunoreactivity was found in the cytoplasmic matrix. In addition, immunoreactivity of intact tissue to endothelin 1, arginine-vasopressin, and substance P was examined and positively staining cells were found to be scattered through the epithelium. CONCLUSIONS: The presence of these vasoactive substances within the epithelium lining the airways supports the view that epithelial cells may provide an additional mechanism in the control of airways reactivity. PMID- 1283646 TI - Nodular lesions of the liver in multiple myeloma: a role for cytoadhesion molecules? AB - Two patients with multiple myeloma and in vivo macroscopic nodular lesions of the liver are presented. The clinical aspects of this very unusual condition are briefly reviewed. In particular, the expression on neoplastic plasma cells of the cytoadhesion molecules CD56 and CD11a, which are involved in the cellular process of recirculation and homing, suggests a possible role for such markers in this atypical localization of the disease. PMID- 1283647 TI - Epirubicin, methotrexate and bleomycin (EMB) in the treatment of recurrent epidermoid cancer of the head and neck. AB - During the period May 1989 to November 1990, at the "O. Alberti" Radium Institute of Brescia's General Hospital, 35 patients affected by epidermoid head and neck carcinoma were treated every 28 days with the salvage chemotherapy regimen EMB (epirubicin, 50 mg/m2 i.v. day 1; methotrexate, 40 mg/m2. i.v. days 1, 18; bleomycin, 10 mg/m2 i.v. days 4, 11, 18). Sixteen patients had been previously treated with surgery, 15 with radiotherapy and 4 with chemotherapy. Six patients (Group A) received only 1 cycle of chemotherapy because of disease progression and subsequent death. In another 15 patients (Group B) it was possible to administer 2 cycles of EMB, and 9 of them showed local disease progression and died. Among the remaining 6 patients, evaluated as PR, 1 refused further therapy and 5 were amenable to a previously impossible radiotherapy (4 of them are still alive). Fourteen patients received 3 or more cycles of EMB (Group C): 8 subjects showed progression and died; 1 reached CR and is alive without any evidence of tumor; 5 are in PR (3 of them underwent subsequent radiotherapy and 1 chemotherapy with CDDP). Out of 35 patients, 12 (34%) reached a favorable response (CR or PR) and 8 (22%) are still alive. As regards toxicity, the following adverse events were recorded (< or = 2 Miller's scale): leukopenia (8.5%), thrombocytopenia (5.7%), anemia (14.2%), stomatitis (5.7%), vomiting (5.7%), alopecia (8.5%), and fever (11.4%). It can be concluded that the EMB regimen is very well tolerated and shows good effects in the treatment of patients with relapsed head and neck carcinoma. PMID- 1283648 TI - Making research work for you. The how-to of a poster session. PMID- 1283649 TI - [Treatment of apoplexy with hypervolemic hemodilution]. PMID- 1283650 TI - [Palliative therapy of central bronchial carcinoma]. PMID- 1283651 TI - [Vibration therapy in gynecology]. PMID- 1283652 TI - [Calcium antagonists--determination of current status and therapeutic significance]. AB - The important group of drugs known as calcium antagonists is surveyed from a clinico-pharmacological viewpoint. The recently introduced substances are presented in a detailed manner. Common features and differences in pharmacodynamics and pharmacokinetics of the individual calcium antagonists are explained and their differential therapeutic use in the treatment of chronic cardiovascular diseases is discussed. The article also reports on drug interferences, contraindications and possible extensions of indications. An assessment is made of results achieved so far when applying calcium antagonists in the treatment of chronic cardiovascular diseases and in the prevention of arteriosclerosis. PMID- 1283653 TI - [Results of prostatectomy in the treatment of obstructive benign prostatic hypertrophy]. AB - Aimed to evaluate the results of surgery in patients with obstructive prostatic hypertrophy, we studied the clinical and flow measure results from 51 patients undergoing prostatectomy (31 TUR, and 20 retropubic prostatectomies). It was shown that prostatectomy significantly improved the irritation (63% of patients), and most importantly, the obstructive (89%) symptoms. Peak flow increased in 100% of patients while maximum flow percentile in 92% of patients. Post-operative results showed no correlation to the patients' age, duration of evolution or severity of urinary symptoms, weight of prostate removed or histology of the prostate. Our results were compared with those obtained with other therapeutical options, and it was demonstrated that prostatectomy (both retropubic and RUT) are, clinically and urodynamically, the most effective procedure in the treatment of obstructive prostate hypertrophy. PMID- 1283654 TI - [First results of our experience with the Fabian's prosthesis]. AB - Report on our experience with Fabian's prothesis as alternative therapy to benign prostate hyperplasia (B.P.H.) surgery. Throughout 1990 ten patients with various surgical contraindications were implanted the above device. In spite of the series small size (10 patients) and short follow-up (4 to 11 months), we believe the 70% good results obtained is very encouraging and can either be of help to banish the ominous indwelling vesical catheter, a permanent evidence of Urologists' failure in the prostate obstructive disease, or it will allow us to relief patients with B.P.H. non-secondary to other more aggressive therapies. PMID- 1283655 TI - Assessment of sperm cell membrane integrity in the horse. PMID- 1283656 TI - Codfish allergy in adults. Identification and diagnosis. AB - Ten adult patients with a medical history of immediate allergic reactions following ingestion of minute amounts of codfish were examined together with 27 control subjects (8 nonatopics, 7 pollen allergics, and 12 suffering from atopic dermatitis) all regularly ingesting codfish without experiencing reactions. All 37 subjects were evaluated by skin prick test, RAST, and histamine release test in order to determine the value of these commonly used diagnostic tests. The results were compared to titrated, oral, double-blind, placebo-controlled food challenges (DBPCFCs) with fresh codfish undertaken in the 10 patients, whereas all control subjects were classified as challenge-negative according to their questionnaires. Totally, 7 of 10 medical histories were confirmed by DBPCFC, and in these most of the reported symptoms proved reproducible. Oropharyngeal itching and swelling occurred as the first symptom, always preceding the onset of any accompanying symptom. For identification of DBPCFC-positive subjects, skin prick test and RAST proved to be the most sensitive tests (7/7), and all tests showed specificities of 90-97%. The skin prick test still seems reliable but does not, however, exclude the need for DBPCFC. PMID- 1283657 TI - Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits. AB - Histamine release (HR) studies were performed in 40 birch pollen-allergic patients (positive case history, positive SPT, positive birch pollen-specific serum IgE: RAST > or = 3) with (n = 20, A) and without (n = 20, B) fruit hypersensitivity, and 10 nonatopic volunteers (C). Several fruit allergens were used and characterized by protein determination and immunoblot techniques. Dose dependent HR (apple peel = apple pulp > peach = cherry) was demonstrated in both allergic groups, but to a higher extent in patients with fruit allergy (P < 0.01). Increased basophil sensitivity to birch pollen was found in the group with fruit allergy (P < 0.001). Strong correlations between the mediator response induced by several fruits indicate common allergens within the extracts. We conclude that fruit-related symptoms require not only high specific serum IgE, but a strong cellular sensitization to birch pollen allergens together with an increased cellular reactivity to fruit allergens. PMID- 1283658 TI - Effect of astemizole on antigen-mediated histamine release from the blood of patients with allergic rhinitis. AB - The main objective of this study was to test the effectiveness of astemizole in vitro in blocking the release of histamine from blood of patients with allergic rhinitis. The results of this investigation indicated that astemizole inhibited allergen-mediated histamine release from blood basophils of patients with this allergic disorder. The inhibition by astemizole (33-156 mumol) was immediate, requiring no pre-incubation of the cells, and was dose-dependent, with maximal inhibition of about 91%. The relatively high potency of astemizole in inhibiting the immunologic release of histamine may provide an additional measure in the treatment of allergic rhinitis with this H1-receptor antagonist. PMID- 1283659 TI - Histamine release in immediate-type hypersensitivity reactions in intact human skin measured by microdialysis. A preliminary study. AB - The purpose of this study was to evaluate the application of a microdialysis technique for measurement of interstitial histamine levels in intact human skin. Three allergic subjects were investigated. Single dialysis fibers were glued to nylon tubings and inserted in forearm skin by means of a fine cannula. Dialysis fibers were inserted in triplicate and perfused with isotonic saline at a rate of 3 microliters/min. After a period of 2 h a 60-microliters base-line period was established. Then the patients were skin prick tested (SPT) with allergen in duplicate and a single saline control. Dialysate was collected in consecutive 30 microliters fractions. Histamine concentration in the dialysate was analyzed with a glass fiber fluorescence assay. Median base-line histamine level was 4 (range 4 7) ng/ml. Following allergen SPT, dialysate histamine concentration increased to 81 ng/ml (74-128), with maximum values 10-20 min after SPT. Intraindividual coefficient of variation on peak histamine levels was 18.9%. No histamine increase was seen following saline SPT. We consider microdialysis to be a valuable method for assessment of allergic mechanisms in intact human skin. PMID- 1283660 TI - Contact allergy to budesonide contained in a nasal spray. AB - We describe a case of contact allergic sensitization to budesonide in a nasal spray used in the treatment of allergic rhinitis. No cross-sensitivity to other topical corticosteroids was found. PMID- 1283661 TI - [Comparison of the effects of epsilon-aminocaproic acid and aprotinin on intra- and postoperative bleeding in heart surgery]. AB - Excessive bleeding during and after cardiac surgery with cardiopulmonary bypass is a real problem in this kind of surgery. The use of prophylactic high doses of aprotinin (APROT) reduces blood loss in this context but this treatment is expensive. Some investigators have advocated that epsilon-aminocaproic acid (EACA), a cheaper antifibrinolytic drug, could reduce blood loss in cardiac surgery. The goal of this prospective study was to determine if EACA is as effective as APROT for this clinical condition. Sixty patients undergoing elective surgery for cardiac disease were randomly allocated to one of the two groups. Drugs were administered after induction of anesthesia at a dose of 2.10(6) UIK in the APROT group or 5 g in the EACA group. The same dose was added to the priming of the cardiopulmonary bypass circuit. Until the skin closure the patients received 5.10(5) UIK/h of APROT or 2 g/h of EACA. Bleeding during and after surgery was not different between the two groups. No complication, directly due to the treatment administered, was observed. EACA seems to be as effective as APROT to reduce intra and post cardiac surgery blood loss. EACA has the advantage of being cheaper (treatment is approximately 200 times cheaper), therefore allowing a wider use. PMID- 1283662 TI - The changing pattern of infantile intussusception in northern Nigeria: a report of 47 cases. AB - Infantile intussusception is not rare in Africa, but was reported to be relatively uncommon. This retrospective review of 47 infants with the diagnosis of intussusception included 38 boys and nine girls. Surprisingly, the clinical presentation is at variance with previous reports and beliefs about intussusception in tropical Africa, but is similar to those from Europe and North America. Contrary to expectation, about 70% of infants presented with the classical clinical picture of intussusception with the complete features of vomiting, 'colicky abdominal pain', blood mucoid stools and palpable abdominal mass. The other 30% presented with various combinations of the components of the tetrad. The small bowel was the leading point in 30 infants and the colon in 17. Of the small bowel variety, the two main types were the ileo-ileal and the ileocolic, while the ileocaecal and the various types of colo-colic intussusception were of large bowel origin. Morbidity was minimal. There were four deaths. Intussusception in this series differs in many respects from previous experience in Zaria. PMID- 1283663 TI - Evaluation of malto-dextrin/glycine oral rehydration solution. AB - The efficacy and safety of malto-dextrin/glycine-based oral rehydration solution (ORS) when compared with the glucose-based oral rehydration solution (WHO) was evaluated in a randomized double-blind clinical trial. Thirty-one subjects and 31 controls were studied. The mean values of the ORS intake, stool output, duration of diarrhoea, urine output, weight gain and serum electrolytes were comparable in both the study and the control groups (p > 0.05). It was found that the malto dextrin/glycine ORS offered no therapeutic advantage over the standard glucose ORS (WHO). In view of the accidental preponderance of children of significantly lower nutritional status among the control group (p < 0.05), it is likely that the efficacy of malto-dextrin/glycine ORS might actually be less than that of the glucose ORS. PMID- 1283664 TI - Is cow's milk suitable for the dietary supplementation of rural Gambian children? 1. Prevalence of lactose maldigestion. AB - To define the age-related prevalence of lactose maldigestion (LM), 218 children aged 13-72 months from a rural Gambian village were studied using a lactose breath hydrogen test. There was a significant rise in LM from 21% to 76% between the 2nd and 3rd-5th years of life (p < 0.001). Only eight children had diarrhoea within 2 weeks before the test. Diarrhoea and abdominal discomfort followed in only seven children (3%). There was no difference in mean time of introduction of supplementary diet or cessation of breastfeeding between children aged 12-36 months with lactose digestion and LM. There was a greater proportion of children with normal lactose digestion than with LM in those still receiving breast milk (85% vs 15%), and a greater proportion of LM in the fully weaned group (63% vs 37%) (p < 0.001). There was no relation between weight-for-age or weight-for height and the ability to digest lactose. The ability to digest lactose is lost in the majority of children during the 2nd year, coincident with the cessation of breastfeeding, but is not a major factor associated with growth failure thereafter. PMID- 1283665 TI - Is cow's milk suitable for the dietary supplementation of rural Gambian children? 2. Patterns of cow's milk intake. AB - Cow's milk has been advocated as a source of supplementary diet for children in many parts of the developing world. The frequency and forms of cow's milk intake and the factors regulating its availability and consumption by 507 children aged up to 6 years in three Gambian villages were measured. Nineteen per cent of mothers did not give cow's milk to their children. Of 413 children taking cow's milk, 41% consumed it only once a week, 32% two to four times a week, 19% once a day and 8% more than once a day. Eighty per cent of children took both fresh and sour milk. Forty-one per cent of infants up to 1 year old received cow's milk at some time. There was a decrease with age in the proportion of children taking fresh milk and a rise with age in the proportion taking sour milk alone (p < 0.001) and both forms of milk. Only 2% of children were reported to have an adverse reaction to fresh cow's milk. The main factors affecting intake were the availability of money and milk. The consumption of cow's milk in early life is common and free of adverse effects. When it is available, it should be used to supplement the diet of the weaned child. PMID- 1283666 TI - Purulent meningitis in children: outcome using a standard management regimen with chloramphenicol. AB - We report a prospective study of 108 children aged from 2 weeks to 10 years with purulent meningitis admitted to the children's wards of Port Moresby General Hospital, 105 of whom were treated with a standard management regimen using chloramphenicol (given intramuscularly initially) as the only antibiotic. The case fatality rate of 16.7% and the apparently low morbidity rate were felt to be very satisfactory in a high risk population. The medical officers' compliance with the standard antibiotic regimen was good, but was disappointing for the use of anticonvulsants. The presence of convulsions before admission or at any time in the illness, coma on admission, and a history of illness of more than 3 days duration prior to admission were strongly associated with death. We believe phenobarbitone should be given prophylactically to children less than 2 years of age who have meningitis. Further improvements in outcome are likely to be achieved not by changes in antibiotic policy but by improving early diagnosis and basic supportive care, and by preventing convulsions. PMID- 1283667 TI - Indications for lumbar puncture in children presenting with convulsions and fever of acute onset: experience in the Children's Emergency Room of the University of Benin Teaching Hospital, Nigeria. AB - A total of 522 children, aged 1 month to 6 years, who presented with convulsions and fever of acute onset at the Children's Emergency Room of the University of Benin Teaching Hospital over a 1-year period, were prospectively evaluated. Bacterial meningitis was diagnosed in 22 (4.2%) on bacteriological and/or biochemical evidence. The causative organisms were cultured from the CSF in 13 (Neisseria meningitidis = 7, Streptococcus pneumoniae = 5 and Haemophilus influenzae = 1) and identified by Gram stain only in three (Gram-positive diplococci = 2 and Gram-negative diplococci = 1). No organisms were identified in the CSF of six of the children with meningitis. The prevalence of meningitis declined sharply after 6 months of age. Six of the children with bacterial meningitis lacked classical meningeal signs but had other indications for lumbar puncture. The following were significantly associated with meningitis: age under 6 months; focal or multiple seizures; absence of a past or family history of seizures; unrousable coma; and an extracranial focus of infection. It is concluded that bacterial meningitis occurs in a good proportion of children, even beyond infancy, with convulsions associated with fever of acute onset, and that decision on the need for lumbar puncture should be guided by clinical features such as age and the presence of complex febrile seizures. PMID- 1283668 TI - Screening for glucose-6-phosphate dehydrogenase deficiency can prevent severe neonatal jaundice. AB - Infants with the severe variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop hyperbilirubinaemia sufficiently severe to cause kernicterus and death, acute haemolysis on exposure to oxidant stress, congenital non-spherocytic haemolytic anaemia and, rarely, increased susceptibility to bacterial infection. In spite of these potential problems, G6PD deficiency is often not included among screening programmes for inherited disorders. In a comprehensive screening and educational programme, we tested around 34,000 infants for G6PD deficiency. Of the total group, 18.4% (24.5% boys and 11.8% girls) were deficient. Forty-two of the 6246 (0.67%) G6PD-deficient infants required exchange transfusion. None of them developed kernicterus. By contrast, of 4755 infants who had not been screened because they were born at home, three developed kernicterus. In addition, four G6PD-deficient infants had developed kernicterus in the 20-month period prior to the screening programme. None of the hyperbilirubinaemic infants had blood group incompatibility or any other identifiable cause of hyperbilirubinaemia. To avoid this disastrous result, we believe that neonatal screening for G6PD deficiency, together with a comprehensive education programme, is advisable in those parts of the world where the severe variant of G6PD deficiency is prevalent. PMID- 1283669 TI - Acquired immunodeficiency syndrome: education exposure, knowledge and attitude of Nigerian adolescents in Calabar. AB - The knowledge of and attitude to acquired immunodeficiency syndrome (AIDS) of 738 secondary school youths in Calabar were studied by questionnaire in March 1991. Most (92%) of the adolescents had heard about AIDS, largely through the mass media (79-85%), with parents and teachers contributing in less than 40%. About 30% did not know that AIDS exists in Nigeria. Most of them knew that promiscuity, blood transfusion and sharing injection needles and syringes are the major modes of transmission, but a number still incriminate toilet seats, eating utensils, hand-shaking and kissing. Only 31% were aware that condoms provide protection. For self-protection the youths prefer abstinence (45%) and confinement to one sex partner (19%). Only 3.6% would adopt the use of condoms. To prevent the spread of AIDS, the youths prescribe isolation (37%), treatment (34%), and killing (14%) of diagnosed cases. Most youths (77%) will stop seeing friends and 63% will reject relatives who develop AIDS. The study reveals that while general awareness of AIDS is fairly good, detailed knowledge is riddled with misconceptions and confusion. It is recommended that physicians in the community should assist in disseminating accurate information, with the support of parents, teachers and the youths themselves. PMID- 1283670 TI - Preterm infants with patent ductus arteriosus: treatment with an enteral preparation of indomethacin. AB - Forty-one preterm infants with a mean gestational age and birthweight of 29.7 weeks and 1322 g, respectively, were treated with an enteral preparation of indomethacin for the closure of haemodynamically significant patent ductus arteriosus. The indomethacin was prepared by diluting the content of the commercially available 25-mg indomethacin capsule with lactose by the method of trituration. The mixture was suspended in solution form just prior to administration to the infants. The ductus arteriosus was successfully closed in 29 infants, giving an overall success rate of 71%. The response to treatment was considered satisfactory, except for infants whose birthweights were less than 750 g. Only two infants (5%) developed major complications, both in the form of ileal perforation. As the outcome of treatment with this enteral preparation of indomethacin was comparable with that of the intravenous preparation reported in previous studies, it would be an acceptable alternative to the intravenous preparation in areas where the latter is not available or considered expensive. PMID- 1283671 TI - Rett syndrome in South Africa. AB - Rett syndrome is a fairly recently recognized neurodevelopmental disorder of unknown aetiology that affects exclusively girls in whom early development is apparently normal but by the age of 6-18 months autistic behaviour and dementia, apraxia of gait, stereotypic repetitive hand movements, seizures and deceleration of head growth occur. Except for one Brazilian case, all previous reported cases have been from the northern hemisphere. We report three children (two Indian and one African) with the clinical features of Rett syndrome and believe these to be the first documented cases in Indian and African children in the southern hemisphere. More widespread knowledge of this syndrome is required, especially in developing countries, in order to prevent unnecessary and costly investigations, and to help families deal effectively with this important syndrome. PMID- 1283672 TI - Giant lipoblastoma: a case report. AB - A Nigerian boy presented to the paediatric surgical unit of this institution with what appeared to be a malignant congenital mesenchymal neoplasm of the right axilla. The mass was lipofibromatous and invaded local structures. Excision was complete. The specimen weighted 4 kg. Histological features were those of a lipoblastoma. Following excision, he had a neurological deficit involving the 4th and 5th cervical neural segments which persisted till he was lost to follow-up 2 years later. PMID- 1283673 TI - The association of household pollutants and socio-economic risk factors with the short-term outcome of acute lower respiratory infections in hospitalized pre school Nigerian children. AB - In a 9-month study of acute lower respiratory infections (ALRI), the short-term prognostic implications of socio-economic and household risk factors were examined in 103 hospitalized pre-school Nigerian children. Seventy-nine (77%) subjects were potentially exposed to the combustion products of kerosene stoves, 16 (16%) to wood smoke and five (5%) to the products of cooking gas combustion. Only 17 subjects (17%) were exposed to household cigarette smoke. A highly significant association (p < 0.005) was shown between household cooking fuel and the outcome of hospitalization: five (63%) of the eight who died were potentially exposed to wood smoke. The duration of hospitalization was only significantly associated with paternal income (p < 0.05). None of the other domestic risk factors was significantly related to outcome or duration of admission. These findings suggest an association between an adverse outcome of ALRI and domestic exposure to wood smoke. While the hospital-based source will not allow definite conclusions, the present findings underscore the need for community-based studies. The implications for future strategies of ARI control are discussed, with suggestions. PMID- 1283674 TI - Bacteraemia in severely malnourished children. AB - During a 2-year period, 792 severely malnourished children (kwashiorkor, marasmus and marasmic kwashiorkor) were hospitalized (14.8% of all admissions). Community acquired bacteraemia was recorded in 7.7% and nosocomial bacteraemia in 2.2% of malnourished children. The relative risk for bacteraemia on admission was 1.6 (95% confidence interval [CI] 1.3-1.9) and 2.0 for nosocomial bacteraemia (95% CI 1.4-3.0) in malnourished children as compared with well nourished children. Bacteraemia was 3.5 times more common in children with kwashiorkor than in marasmic children. Gram-negative enteric aerobes were isolated 2.6 times more frequently from malnourished than from well nourished children. The relative risk of death in malnourished children with bacteraemia was 2.5 times that of malnourished children without bacteraemia. Thirty-six per cent of deaths in children with kwashiorkor were related to bacteraemia. This study emphasizes the increased risk of bacteraemia in malnourished children, particularly those with kwashiorkor, and the impact on mortality. PMID- 1283675 TI - Plasma levels of mebendazole in children with hydatid disease. AB - The plasma levels of mebendazole in children with hydatid cyst disease were measured with high pressure liquid chromatography. In 24 children who received mebendazole orally in a dose of 50 mg/kg, the mean (SD) level 4 hours later was 25.76(9.81) ng/ml (87.6(33) nanomole/l). This result was similar to those in most adult series. During more prolonged treatment, the plasma level 4 hours after the dose of the drug rose significantly with respect to the initial level (p < 0.05). PMID- 1283676 TI - Neonatal and post-neonatal onset of early congenital syphilis: a report from Mozambique. AB - Congenital syphilis (CS) has been and continues to be a principal public health problem in developing countries. Despite the wide experience acquired, physicians still have problems in diagnostic evaluation. We report 145 cases of CS at the Central Hospital, Maputo, emphasizing the differences in clinical features and in the results of serological and X-ray examinations between the neonatal and post neonatal age groups. In the post-neonatal age group, the clinical expression of CS is mostly overt. It is commonly recognized that manifestations of CS in the neonatal age group are often poor or negative, yet a relevant percentage of CS that we report were fully symptomatic. In the neonatal age, the Venereal Disease Research Laboratory (VDRL) test in the mother and characteristic osteochondritic lesions on X-ray examination of the long bones help to make the diagnosis; in the post-neonatal age group, the VDRL test in the child is more often positive than in the mother and X-ray examination shows most periostitic lesions. PMID- 1283677 TI - Pyogenic liver abscess causing acute Budd-Chiari syndrome. AB - Acute Budd-Chiari syndrome caused by compression of the inferior vena cava by a space-occupying lesion in the liver is rare in children. We report a case where the compression was due to a large staphylococcal abscess in the right lobe of the liver. A high index of suspicion in such a case ensures early intervention and saves life. PMID- 1283678 TI - Hyponatraemia and the inappropriate ADH syndrome in pneumonia. AB - We studied serum sodium, plasma osmolality and urinary sodium and osmolality on days 1, 3 and 5 of hospitalization of 100 children aged from 1 month to 12 years admitted with a diagnosis of pneumonia. Hyponatraemia (serum sodium concentration < or = 130 mmol/l) was found in 31 patients at the time of admission. The probable cause of hyponatraemia in 94% of cases was the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Symptoms and signs indicative of severe pneumonia were two to three times more frequent and the mean duration of tachypnoea, chest-wall retraction and hospital stay about one and a half times longer in children with hyponatraemia. Four children died (two on day 1, one on day 5 and one on day 8); all four had a serum sodium concentration < or = 125 mmol/l which persisted until death. Of the remaining 27 hyponatraemic children, serum sodium concentrations returned to normal on day 3 in 26, while in one hyponatraemia persisted until day 7. The recovery from hyponatraemia showed a good correlation with improvement in clinical signs of respiratory distress. The SIADH occurred in about one-third of the children hospitalized for pneumonia, and was associated with a more severe disease and a poorer outcome. Perhaps fluid restriction in these cases may improve the outcome. PMID- 1283679 TI - Increase in total serum triglyceride and phospholipid in kwashiorkor. AB - Fasting serum lipids in children presenting with protein-energy malnutrition were studied in comparison with those of sex- and age-matched well nourished controls. There was no difference in serum total cholesterol between malnourished and well nourished children. However, serum triglyceride and phospholipid concentrations were significantly higher in children with kwashiorkor or marasmic kwashiorkor than in well nourished controls. It appears that serum concentrations of triglycerides and phospholipids increase with increasing severity of malnutrition, and that fasting serum triglyceride and phospholipid concentrations above 3 mmol/l are jointly predictive of a poor prognosis in malnourished children. PMID- 1283680 TI - Nutritional pattern and eco-physiology of Hortaea werneckii, agent of human tinea nigra. AB - The life cycle of Hortaea werneckii includes yeast-like, hyphal and meristematic growth. The preponderance of each form of propagation can be influenced by environmental conditions. The clinical entity 'tinea nigra' is explained by ecological similarities between supposed natural niches and human hyperhydrotic skin. The species is recognizable by assimilation of lactose, nitrate and nitrite, no or little growth with L-lysine, cadaverine, creatine and creatinine, and tolerance of 10% NaCl. It generally does not grow at 36 degrees C. PMID- 1283681 TI - Role of prostanoids in the inflammatory reaction and their therapeutic potential in the skin. AB - Vasodilatory prostaglandins (PG), contributing to the inflammatory reaction, have gained considerable attention. It is becoming apparent that PG have pharmacological effects traceable to biological activities distinct from smooth muscle relaxation. The data from pharmacological experiments presented here indicate the diverse action of vasodilatory PG analogues in the skin of laboratory animals. Nocloprost, a stable PGE2 analogue, induced erythema in intact skin of rats when applied topically and inhibited in the same dose range an irritant-induced inflammatory reaction in the ears of mice. Iloprost, a stable PGI2 analogue, showed proinflammatory activity after local application by enhancing the leukotriene B4 induced cell infiltration in the skin of mice. The attenuation of the spreading of ear necrosis in mice, on the other hand, indicates an anti-ischemic therapeutic potential of iloprost. Research in the past has elucidated the influence of PG on the vascular component of inflammation, but the role of PG on the cellular component of inflammation is less clear. The diverse effects of PG in skin indicate the need for a better understanding of their local actions. PMID- 1283682 TI - The Hopkins Lupus Pregnancy Center: 1987-1991 update. AB - The course of pregnancy in patients with systemic lupus erythematosus is not known. The Hopkins Lupus Pregnancy Center has followed 64 patients (74 pregnancies) prospectively since 1987. Patients are seen monthly and clinical and pregnancy-related data collected, with particular emphasis on the occurrence of lupus flare. Flare rate during pregnancy was 1.63 per person-year, compared to 0.64-0.65 after delivery or in non-pregnant patients. Flare did not influence pregnancy outcome. Low serum C3 or C4 and high anticardiolipin antibody predicted pregnancy loss, and prednisone dose, aspirin use, diastolic second trimester blood pressure, C3 at first visit, and race predicted preterm birth. Maternal flare and preterm birth are important risks in lupus pregnancy. The latter can be predicted from maternal pregnancy data. PMID- 1283683 TI - Effects of muscarinic receptor agonists and antagonists on rat brain serotonergic activity. AB - The effects of some muscarinic M1 and M2 receptor agonists and antagonists on rat brain serotonergic activity was assessed by noting their effects on the levels of 5-hydroxytryptamine (5-HT) and its major metabolite, 5-hydroxyindole acetic acid (5-HIAA), estimated by a high pressure-liquid chromatographic (HPLC) technique. The muscarinic M1 receptor agonists, arecholine and McN-A-343, and the M2 receptor agonists, gallamine and AF-DX 116, induced a dose-related decrease in the concentrations of both 5-HT and 5-HIAA. On the contrary, scopolamine and the selective M1 receptor antagonist, pirenzepine, increased the levels of the amine and its metabolite. The anti-cholinesterase agent, physostigmine, and the putative M2 receptor agonist, carbachol, induced a dose-related dual effect, with the smaller doses decreasing and the higher doses increasing 5-HT and 5-HIAA concentrations. The results indicate that an inverse relationship exists between the cholinergic and serotonergic neurotransmitter systems in the rat brain due to the likely presence of muscarinic heteroreceptors on serotonergic neurones. The data also indicates that though physostigmine and carbachol may function as M2 receptor agonists, they lose their receptor specificity on dose increment. PMID- 1283684 TI - Repeated batch cultivation of rBHK cells on Cytodex 3 microcarriers: antithrombin III, amino acid, and fatty acid metabolic quotients. AB - Anchorage-dependent human antithrombin III-producing recombinant baby hamster kidney (rBHK) cells were cultivated on Cytodex 3 microcarriers in repeated batch mode. During a 3-month experiment four different low-serum (0.025% fetal bovine serum) or serum-free medium formulations were evaluated for (a) the initial growth phase of cells and (b) the subsequent production phase, whereby two free fatty acid (FFA) supplements were examined with respect to their growth-promoting and product-formation-enhancing properties. Selected nutrient and (by)product consumption and production rates (including those for antithrombin III, amino acids, and fatty acids) are reported. The calculated metabolic quotients reflect the prevailing slow growth conditions (mu approx. 0.06 day-1) associated with microcarrier cultures. Specific antithrombin III productivities vary significantly as a function of the feed medium supplementation with FFA. PMID- 1283685 TI - [A case of primary intracranial malignant melanoma showing leptomeningeal dissemination]. AB - A 28-year-old woman was hospitalized in drowsy state with signs of increased intracranial pressure. CT scans revealed diffuse increased density with marked enhancement in the subarachnoid space, as well as ventricular dilatation. V-P shunt operation was performed to control intracranial pressure. Repeated cytological examinations of CSF couldn't determine the tumor origin. CT scan of thoracic spine showed a cystic tumor in its dorsal aspect. T2-weighted MRI revealed multiple spotty low intensity, specific to melanin granules, throughout the whole spine. Her thoracic spine was explored, and the intradural tumor was partially removed. Histopathological examination revealed the tumor cell which had dark nucleus with conspicuous nucleolus and cytoplasmic granules. These findings were compatible with malignant melanoma. Her general condition were deteriorated progressively and she died about 5 months after her admission. Postmortum examination showed diffuse leptomeningeal invasion of dark tumor throughout the entire central nervous system, and metastasis to peritoneum and omentum via V-P shunt system. Histopathological examination proved the tumor to be malignant melanoma. Electrone microscopic examination also revealed melanosome in the cytoplasm. Primary intracranial malignant melanoma is divided in two groups, nodular type and leptomeningeal type. In the latter type, early diagnosis is very difficult, just as in our case, because only a little tissue specimen can be obtained. In a case of leptomenigeal carcinomatosis, possibility of primary malignant melanoma, though rare, should always be kept in mind, and specific staining such as Fontana-Masson's staining should be tried. PMID- 1283686 TI - Evaluation of a microcarrier process for large-scale cultivation of attenuated hepatitis A. AB - Microcarrier culture was investigated for the propagation of attenuated hepatitis A vaccine in the anchorage-dependent human fibroblast cell line, MRC-5. Cells were cultivated at 37 degrees C for one to two weeks, while virus accumulation was performed at 32 degrees C over 21 to 28 days. The major development focus for the microcarrier process was the difference between the cell and virus growth phases. Virus antigen yields, growth kinetics, and cell layer/bead morphology were each examined and compared for both the microcarrier and stationary T-flask cultures. Overall, cell densities of 4-5 x 10(6) cells/ml at 5-10 milligrams beads were readily attained and could be maintained in the absence of infection at either 37 degrees C or 32 degrees C. Upon virus inoculation, however, substantial cell density decreases were observed as well as 2.5 to 10-fold lower per cell and per unit surface area antigen yields as compared to stationary cultures. The advantages as well as the problems presented by the microcarrier approach will be discussed. PMID- 1283687 TI - Three-dimensional reconstruction of a complex of human alpha 2-macroglobulin with monomaleimido Nanogold (Au1.4nm) embedded in ice. AB - Cysteine 949 and glutamine 952 are known to be part of the thiol ester site of each of the four subunits of human alpha 2-macroglobulin (alpha 2M). The hydrolysis of this thiol ester bound to methylamine results in the incorporation of the amine and liberation of a free sulfhydryl group that can be specifically labeled. Therefore, a high-resolution marker specific for the sulfhydryl groups, the monomaleimido Nanogold (Au1.4nm) cluster was used to bind this amino acid. After cryoelectron microscopy, a three-dimensional reconstruction of the alpha 2M Nanogold conjugates (alpha 2M-Au1.4nm) was achieved, revealing the internal location of the thiol ester sites in the transformed alpha 2M molecules. From this study we propose three possible locations for the cysteine 949. PMID- 1283688 TI - Competition of Mn2+ and Zn2+ with 59Fe2+ and 59Fe3+ for the plasma membrane receptors from lactating mouse mammary gland. AB - Nonlabeled MnCl2 and ZnSO4 compete with 59Fe(2+)-ascorbate and 59Fe2(3+)O3 for transport binding sites situated on the plasma membranes of lactating mouse mammary gland cells. The binding was found to be a process reaching saturation. The heterologous competition used here ruled out the participation of transferrin and to propose that Fe, Mn, and Zn are transported from blood to milk by a mechanism involving one receptor during lactation. Further experiments are necessary to establish the details of the transport mechanism. PMID- 1283689 TI - Tissue antioxidant status in streptozotocin-induced diabetes in rats. Effects of dietary manganese deficiency. AB - Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn deficient or Mn-sufficient diets for a total of 12 wk. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copper-zinc superoxide dismutase (CuZnSOD) in kidney, in the non diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H2O2-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time and interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient. PMID- 1283690 TI - Studies of the interaction between boron and calcium, and its modification by magnesium and potassium, in rats. Effects on growth, blood variables, and bone mineral composition. AB - Two experiments were performed to confirm that boron interacts with calcium, and that this interaction can be modified by dietary magnesium and potassium in the rat. Upon manipulating the dietary variables listed above, it was found that under certain conditions, boron and calcium deprivation similarly affected several variables; for example, they both could be made to elevate plasma alkaline phosphatase activity and to depress femur calcium concentration. Under some dietary conditions, both boron and calcium deprivation affected some variables related to blood or iron metabolism. However, the effects of dietary boron and calcium on spleen weight/body weight ratio, hematocrit, and femur iron concentration generally were not similar. Femur copper, magnesium, phosphorus, and zinc also were affected by an interaction between boron and calcium under some dietary conditions. The findings show that there is a relationship between boron and calcium, but they do not clearly indicate the nature of the relationship. However, the data suggest that boron and calcium act on similar systems in the rat. PMID- 1283691 TI - The effect of time of introduction of a high-fructose, low-copper diet on copper deficiency in male rats. AB - The purpose of the present study was to compare the time of introduction of the high-fructose low-copper diet on the expression of copper (Cu) deficiency. Weanling male rats were randomly assigned to either a diet containing 62.7% fructose or starch, and 6.0 (F+Cu) or 0.6 (S-Cu) microgram Cu/g diet, respectively, for either 1, 2, or 3 wk before being transferred to a diet containing fructose and inadequate in copper (F-Cu). At week 10, body weight and relative heart size of rats initially consuming the F + Cu diet was inversely related to the week placed on the F-Cu diet, but not for those initially consuming S-Cu. Hematocrit, hepatic Cu concentration and RBC superoxide dismutase activity were significantly lower in rats initially consuming S-Cu when compared to those fed F + Cu. Mortality was greatest in rats switched to the F-Cu diet at weeks 1 and 2 when compared to those switched at week 3 regardless of the type of diet initially consumed. Plasma cholesterol, triacylglycerols, and blood urea nitrogen concentrations were not significantly altered by the type of diet initially consumed or by the time of introduction of the F-Cu diet. It was concluded that changing rats to a F-Cu diet at 1, 2, or 3 wk after weaning did not significantly improve some of the characteristic signs associated with Cu deficiency, but the later that the F-Cu diet was introduced after weaning the greater the chances for survival. PMID- 1283693 TI - Serum nickel levels of diabetic patients and healthy controls by AAS with a graphite furnace. AB - In this study, serum nickel levels of diabetic patients and healthy controls were determined by AAS with a graphite furnace. The serum nickel concentrations were found to be 1.15 +/- 1.89 micrograms/L in healthy controls and 0.82 +/- 0.74 microgram/L in diabetics. There was, however, no statistically significant difference between the two groups (p = 0.13). The relationship of nickel levels to diabetes type and duration, diabetic complications and treatment, sex, age, and heredity was investigated. However, again no significant differences were found, nor was there any correlation between serum nickel levels and blood sugar, HBa1c, fructosamine, sialic acid levels, and age. PMID- 1283692 TI - Zirconium. An abnormal trace element in biology. AB - The action of Zirconium (Zr) on biological systems presents an enigma. It is ubiquitous, being present in nature in amounts higher than most trace elements. It is taken up by plants from soil and water and accumulated in certain tissues. The entry into animal systems in vivo is related to the mode of exposure and the concentration in the surrounding environment. Retention is initially in soft tissues and then slowly in the bone. The metal is able to cross the blood brain barrier and is deposited in the brain and the placental barrier to enter milk. The daily human uptake has been known to be as high as 125 mg. The level of toxicity has been found to be moderately low, both in histological and cytological studies. The toxic effects induced by very high concentrations are nonspecific in nature. Despite the presence and retention in relatively high quantities in biological systems, Zr has not yet been associated with any specific metabolic function. Very little information is available about its interaction with the compounds of the genetical systems, such as nucleic acids. Apparently, the metal is neither an essential nor toxic element in the conventional sense. However, the increasing exposure to this element through its increasing use in new materials and following radioactive fallout, has increased the importance of the study of its effects on living organisms. The tetravalent nature of the ionic state and the high stability of the compounds formed are important factors that need to be considered, as also the accumulation of this element in the brain, reminiscent of the relationship between Al3+ and Alzheimer's disease. PMID- 1283694 TI - Effects of excess selenomethionine on selenium status indicators in pregnant long tailed macaques (Macaca fascicularis). AB - Forty pregnant long-tailed macaques were treated daily for 30 d with 0, 25, 150, or 300 micrograms selenium as L-selenomethionine/kg body weight. Erythrocyte and plasma selenium and glutathione peroxidase specific activities, hair and fecal selenium, and urinary selenium excretion were increased by and were linearly related to L-selenomethionine dose. Hair selenium was most sensitive to L selenomethionine dose, with an 84-fold increase in the 300 micrograms selenium/(kg-d) group relative to controls (r = 0.917). Daily urinary selenium excretion (80-fold, r = 0.958), plasma selenium (22-fold, r = 0.885), erythrocyte selenium (24-fold, r = 0.920), and fecal selenium (18-fold, r = 0.911) also responded strongly to L-selenomethionine. Erythrocyte and plasma glutathione peroxidase specific activities increased 154% and 69% over controls, respectively. Toxicity was associated with erythrocyte selenium > 2.3 micrograms/mL, plasma selenium > 2.8 micrograms/mL, and hair selenium > 27 micrograms/g. Plasma, erythrocyte, and hair selenium concentrations may be useful for monitoring and preventing the toxicity of L-selenomethionine administered to humans in cancer chemoprevention trials. PMID- 1283695 TI - Selenium in Hungary. The rock-soil-human system. AB - Selenium (Se) status of Hungarian rock-soil systems has been poorly investigated. The goal of this study was to get general information on the main features of Se geochemistry, and to have a brief look into the human Se status in Hungary, developing an appropriate method for a forthcoming systematic regional investigation. A multistage program was applied: 1. stream sediment sampling; 2. investigation of rock-soil profiles typical in Hungary; and 3. extraction of mobile Se fractions from soils. Human serum samples from apparently healthy blood donors residing in both urban and rural areas were collected from three districts in Hungary. It was concluded that Hungarian rock-soil systems, especially the acid igneous rocks and the widely distributed young sediments (loess and sand formations) with most of the agricultural activity, are low in Se, and the mean serum Se level of the blood samples were also low. PMID- 1283696 TI - Prevention of post dural puncture headache with epidural-administered dextran 40. PMID- 1283697 TI - Two modes of homologous C3 deposition on Ramos Burkitt's lymphoma cell substrains co-expressing DAF (CD55), CD59, and CR2 (CD21), and on cells lacking them. AB - We established decay-accelerating factor (DAF)/CD59-positive and -negative substrains of a human B cell line, Ramos, R(DAF+/CD59+) and R(DAF-/CD59-) respectively. Unexpectedly, treatment of R(DAF+/CD59+) cells with Mg2(+)-EGTA serum resulted in efficient C3 deposition, while treatment of R(DAF-/CD59-) cells did not. All six substrains of R(DAF-/CD59-) cells were CR2-negative, and treatment of the cells with M177 [a membrane cofactor protein (MCP) cofactor blocking antibody] and/or acidic buffer only minimally affected the extent of C3 deposition. However, when R(DAF-/CD59-) cells were pretreated with M177 followed by incubation with low conductivity (3 mS) Mg(2+)-EGTA-serum, C3 deposition leading to effective cytolysis was provoked. On the other hand, all seven R(DAF+/CD59+) substrains were CR2-positive and could potentially induce C3 autoactivation without cytolysis under physiological conditions. Both M177 and pH again minimally affected the extent of C3 deposition. However, conductivity altered the sensitivity to C3: at under 3.0 mS, R(DAF+/CD59+) cells became almost insensitive to alternative pathway-mediated C3 deposition. Anti-CR2 partially inhibited C3 deposition on R(DAF+/CD59+) cells and C3 deposition was abrogated on the CR2-lacking R(DAF-/CD59-) cells, suggesting that CR2 was associated with the deposition of C3. These results, together with the finding that fluid phase activation of complement did not enhance C3 deposition, suggest that there are two distinct modes of spontaneous homologous C3 deposition on human lymphoma cells. In one case, CR2 or its related molecules participates in C3 deposition overcoming the protective function of DAF/MCP and this type of C3 deposition is maximized under physiological conditions. In the other case, C3 deposition is induced by another homologous C3 activator that becomes functional under low conductivity conditions and the absence of DAF/MCP. These two modes of homologous alternative pathway activation would explain the reported instances of spontaneous C3 deposition on human B lymphoid cell lines (under physiological conditions in the presence of DAF/MCP) and on paroxysmal nocturnal hemoglobinuria erythrocytes (under low conductivity conditions in the absence of DAF/MCP). PMID- 1283698 TI - Agonist-antagonist interactions in the skin: comparison of effects of loratadine and cetirizine on skin vascular responses to prick tests with histamine and substance P. AB - The skin vascular responses (weal, flare, blood flow measurements) elicited by intradermal administration by pricking of histamine (HS) and substance P (SP) were evaluated 6 h after a single intake of anti-H1 agents displaying different activity profile on skin tests at currently recommended dosages (loratadine 10 mg, cetirizine 10 mg) as compared to placebo (P). The weal and flare response and the increases of blood flow occurring in the usual flare area after HS and SP were almost completely abolished by cetirizine. Inhibition of HS- and SP-induced weal and flare reactions was less marked after loratadine and blood flow in the expanding flare after HS and SP showed significant fluctuations over time. In view of the present results and of data obtained in previous experiments with intradermal injection of agonists, we hypothesize that mode of administration of agonists significantly influences the size of the residual weal after anti-H1 agents. We demonstrate that SP weals induced by pricking are largely inhibited by a potent H1 blockade which supports the view that this phenomenon, as well as the SP-flare, is due to SP-induced histamine liberation. We also, for the first time, report on fluctuations recorded at the edge of the developing flare with laser Doppler flowmetry early after prick testing with a weak H1 blockade. This opens up new avenues in dynamically testing H1-receptor occupancy in vivo and in situ in human skin. PMID- 1283699 TI - Influence of age and gamma irradiation on the proliferative activity in regenerating rat liver. AB - The effect of aging (2-14 months) and total body irradiation (5.7 Gy of gamma radiation) on liver regeneration was investigated in rats 30 h after partial hepatectomy. Exposure of rats to irradiation 30 min before partial hepatectomy caused latent injury in the remaining liver cells. During the course of liver regeneration this became manifested as a delay in increasing the nucleic acid concentration and content and liver weight and, furthermore, as inhibition of the increase in the mitotic index and cellularity and pronounced increase in the frequency of chromosome aberrations in the postmetaphase. The pattern of age related changes during liver regeneration was the same as that after irradiation, so that the differences between irradiated and nonirradiated animals became smaller with age. PMID- 1283700 TI - Mycobacterium malmoense type II bacteraemia contributing to death in a patient with AIDS. PMID- 1283701 TI - The use of octadecyl-bonded microparticulate silica in the separation of free and bound fractions during saturation analysis of vitamin D metabolites. AB - The use of octadecyl-bonded microparticulate silica to separate free and bound fractions during the saturation analysis of 25-hydroxyvitamin D and 1,25 dihydroxyvitamin D has been investigated. A slurry of octadecyl-bonded silica in an appropriate incubation buffer was prepared and used in parallel with a conventional dextran-coated charcoal suspension in several assay procedures. Standard curves, non-specific binding and plasma values were compared. A competitive protein binding assay for 25-hydroxyvitamin D and two radioreceptor assays and one radioimmunoassay for 1,25-dihydroxyvitamin D were investigated. In most cases the octadecyl-bonded silica preparation gave the more favourable results; its action was rapid, time- and temperature-independent, and it produced low non-specific binding and higher B0 values in all the assays examined. It was in our hands easier to use than dextran-coated charcoal. The use of octadecyl bonded silica is recommended as an efficient agent for the separation of free and bound fractions in the saturation analysis of vitamin D metabolites. PMID- 1283702 TI - Anticancer strategies involving the vasculature: vascular targeting and the inhibition of angiogenesis. AB - Progress in our understanding of tumour angiogenesis and an appreciation of the marked differences between quiescent and proliferating endothelium are revealing new strategies for anticancer therapy. This article outlines these strategies and critically assesses their chances of success. PMID- 1283703 TI - Activation of platelet concentrate during preparation and storage. AB - This review will discuss how stored platelets become activated and will examine their ability to function and survive in vivo, posttransfusion. Experimental methods which have been shown to alter platelets during storage will be detailed. Using beta-thromboglobulin (beta-TG) and surface adhesion receptors as markers, investigators have examined the activation changes in platelet concentrates during preparation and storage. Resuspension of the platelet pellet after isolation of platelet-rich plasma appears to play a major role in producing platelet activation and beta-TG release during preparation. However, there is a significant amount of interdonor variability in platelet activation even at this early stage of storage. Over 5 days of storage, platelets release approximately 50% of their beta-TG contents. Furthermore, between 40% and 60% of the platelets express the alpha-granule membrane protein, P-selectin (GMP-140), during storage, which is also indicative of platelet activation. These activation changes correlate to some degree with platelet recovery posttransfusion but clearly do not explain the full lesion of platelet storage. The surface density of two platelet membrane receptors, glycoproteins (GP) Ib and IIb/IIIa, also change with activation, although in opposite directions. Platelet surface GPIb decreases initially with storage and then recovers, perhaps due to its relocation to the platelet surface from an intracellular pool. In contrast to GPIb, mean platelet surface GPIIb/IIIa increases slightly during storage, probably as a consequence of platelet activation and release of alpha-granule GPIIb/IIIa to the surface. Some hypotheses are offered regarding how these activated platelets can continue to circulate after transfusion. Further exploration of the platelet storage lesion will hopefully provide needed answers and thus permit better treatment of hemostatic disorders in the future. PMID- 1283704 TI - Changes in platelet membrane glycoproteins during blood bank storage. AB - The literature on membrane glycoprotein changes occurring during platelet storage is reviewed. Technical problems which may have biased reports are clarified, and the consensus of current studies is established. The membrane alterations that occur during blood bank storage are reminiscent of the surface changes which result from platelet secretion: an increased surface concentration of GP IIb-IIIa and GMP-140, and the appearance of platelet membrane microparticles in the supernatant plasma. The clinical importance of these changes is unknown. Future directions for research on the structure and function of stored platelets are discussed. PMID- 1283705 TI - Matrix-assisted laser desorption/ionization mass spectrometry of nucleic acids with wavelengths in the ultraviolet and infrared. AB - A number of different matrices have been tested and compared for ultraviolet and infrared (UV and IR) matrix-assisted laser desorption/ionization (MALDI) of oligodeoxyribonucleotides and mixtures thereof, as well as ribonucleic acids (tRNA from yeast and rRNA from E. coli). A new technique for removing alkali cations from nucleic acid samples during sample preparation on the sample support is demonstrated. The amount of oligonucleotide sample consumed during a typical measurement in IR-MALDI-MS was determined. PMID- 1283706 TI - Temporal differentiation and migration of substance P, serotonin, and secretin immunoreactive enteroendocrine cells in the mouse proximal small intestine. AB - Precise spatial interrelationships exist between substance P, serotonin, and secretin containing enteroendocrine cells in the gastrointestinal tract of mice. In the proximal small intestine these products are coexpressed in various combinations in single enteroendocrine cells along the crypt to villus axis in a pattern that suggests the sequential expression of substance P, serotonin, and secretin. In this report we use bromodeoxyuridine (BrdU) and multilabeling immunohistochemistry to define the temporal and spatial interrelationships between substance P, serotonin, and secretin immunoreactive cells in the mouse proximal small intestine. Our findings demonstrate the sequential expression of substance P, serotonin, and secretin in a population of upwardly migrating enteroendocrine cells and, furthermore, identify a population of crypt associated cells coexpressing substance P and serotonin that fails to traverse this pathway. The lack of secretin immunoreactive cells in the crypts suggests that local factors present in the crypts and/or on villi regulate secretin expression. The combined use of BrdU and multilabeling immunohistochemistry provides a method for defining enteroendocrine cell differentiation pathways throughout the gastrointestinal tract. PMID- 1283707 TI - [Lymph node metastasis in lobular breast cancer--an immunohistochemical study]. PMID- 1283708 TI - [Behavioral characteristics of homo- and bisexuality affecting the prevalence of HIV infection]. PMID- 1283709 TI - [Clinico-epidemiological analysis of the cases of HIV infection in the north western region of Russia]. AB - The paper provides an epidemiological characterization of HIV infection spread in a Russia's large region with more than 10 million people. The epidemiological findings show that the significant onset of HIV infection occurred among the population in this region in mid 1988. Homosexuals and bisexuals are prevalent among the HIV-infected, sexual contact is the main mode of HIV transmission. In addition to delivery of HIV infection from foreign countries, there are cases of local transmission. The clinical evidence indicates that most HIV-infected people are asymptomatic. Herpes viruses, Mycobacteria tuberculosis, Toxoplasma and fungi are common among causative agents of AIDS-related infections. PMID- 1283710 TI - [Clinical manifestations and the problems of classification of HIV infection]. AB - The clinical manifestations and some immunological parameters (CD4 lymphocytes, CD4/CD8 ratio, IgM, IgA, IgG levels, skin test) were examined in 226 adult patients (148 males and 78 females) infected with HIV. These included 58 (26%) asymptomatic patients with seropositive test, 109 (48%) with the only clinical manifestation generalized lymphadenopathy; 54 (24%) with AIDS-related infections, 5 (2%) with AIDS. A subsequent follow-up of 3 months to 3 years demonstrated that AIDS developed in 7 patients, 9 died. The period of infection with HIV and death ranged from 1.5 to 9 years. The signs of cell immunodeficiency were found in 70% of the examinees. Recommendations are given on the classification of HIV infection. PMID- 1283711 TI - [Hemostatic disorders in patients with HIV infection]. AB - Impaired hemostasis was studied in 50 adult patients with HIV infection. The blood coagulative potential, the number and functional activity of platelets were examined. Platelet aggregation and secretion were shown to change earlier than thrombocytopenia developed and clinical signs of HIV infection appeared. The disturbance in the plasma section of hemostasis are due to concurrent opportunistic diseases and infections. PMID- 1283712 TI - [Immunologic changes in the process of the treatment of children with HIV infection using azidothymidine]. PMID- 1283713 TI - [HIV infection: a case of progressive encephalopathy and Pneumocystis carinii pneumonia in a child]. PMID- 1283714 TI - [Pneumocystis carinii infection in a HIV infection department]. AB - To determine the prevalence of Pneumocystis carinii in the HIV-infection department, a simultaneous survey was made of 33 HIV-infected patients at various stages of the disease, of close relatives that were nursing the patients in the unit (n-7), and of medical staff of the department (n-20). Patients with toxic infections who were on another floor of the same hospital and medical students were examined as a control group. For detection of P. carinii antigen, smears from the deep airways were tested in the immunofluorescence. P. carinii was detected in 87.7% of HIV-infected patients, in 71.4% of their relatives and in 80.0% of the medical staff, in 16.6% of control patients and 27.7% of students. The main type of the infectious process in pneumocystosis is its carriage; 2 patients at a stage of relapses (IIIB) that corresponds to AIDS were recorded as having pneumocystis pneumonia. PMID- 1283715 TI - [AIDS--the global problem of the century. Prospects of the development of AIDS research]. PMID- 1283716 TI - [Clinico-experimental study of mental processes in men with HIV infection]. AB - A total of 55 males aged 19.5 to 62 years who were infected with HIV were examined psychopathologically+ and neuropsychologically by A.R. Luria's methods. Twenty-one of these patients were homosexuals. Syphilis was recorded in 34.7% in this group. Lymphadenopathy was the major clinical sign of HIV infection. Symptoms of organic involvements+ of the central nervous system were revealed by a psychopathological method. Neuropsychological studies detected dysfunction of the right cerebral hemisphere, particularly in a group of homosexuals suffering from syphilis. PMID- 1283717 TI - [Comparative analysis of functional activity of peripheral blood phagocytes in HIV-infected patients and in those with recurrent herpes simplex]. AB - The functional activity of peripheral phagocytes were comparatively studied in 14 HIV-infected patients and 28 patients with chronic Herpes simplex viral infection. The two groups exhibited lowered adhesive capacity of phagocytes, impaired production and excretion of active oxygen metabolites. In addition, the patients with chronic Herpes simplex infection showed much elevated levels of myeloperoxidase and acid phosphatase, which indicated its compensatory pattern. The HIV infected had no enhanced enzymatic activity. One cannot rule out that these differences in the functional activity of phagocytes are associated with different effects of viral peptides on the cellular wall of phagocytes. PMID- 1283718 TI - [Tumor necrosis factor-alpha and interleukin-1beta in the blood plasma of patients with HIV infection]. AB - The paper presents examination findings of 67 HIV-infected patients: 32 children aged 2.5 to 16 years and 35 adults aged 21 to 46 years. The proportion of patients with higher alpha-tumor necrosis factor and interleukin-1 beta increased with progression of the disease, the two parameters being higher in the children than in the adults. A correlation was found between the appearance of cytokines in the plasma and some clinical signs, such as fever, weight loss, anemia, neurological disorders. A parallel study of the patients' immunograms indicated significant correlations between the degree of impairments in the composition of lymphocyte subpopulations and the appearance of plasma cytokines. PMID- 1283719 TI - [Detection of Mycoplasma and its antibodies in the blood of HIV-positive patients and in healthy persons]. AB - The comparative study of HIV-positive and clinically healthy persons has indicated that the antigens of M. pneumoniae, M. fermentans and U. urealyticum are encountered nearly twice more frequently in the blood of HIV-infected patients than in that of healthy individuals. Mycoplasma antibodies are detected in HIV-positive persons 12 times more frequently than in healthy ones. Among the HIV-infected persons there are those who have simultaneously antigens of some Mycoplasma species. PMID- 1283720 TI - [The immunoenzyme test system for detection of HIV-1 antigens based on using immune polyclonal anti-HIV serum and monoclonal antibodies against gene GAG HIV-1 proteins]. AB - The paper describes the enzyme immunoassay system for detection of human immunodeficiency virus antigens, which is based on the use of rabbit anti-HIV antibodies and monoclonal antibodies to HIV-1 gene proteins gag. The system may be useful in the examination of laboratory and clinical samples to reveal both free and conjugated antigens in the composition of immune complexes. The sensitivity of the assay system under development is 0.5 ng/ml at 100% specificity. PMID- 1283721 TI - [Peptides from the principal neutralizing and CD4-binding domain: similar immunoreactive properties and structure pattern]. AB - The human immunodeficiency virus (HIV) proteins gp120 and gp41 are the principal immune target in HIV infection. One of the most important trends in the study of AIDS is linked to the mapping of sites involving in the binding to the cell receptor CD4 and in the induction of virus-neutralizing antibodies (VNA). Recent studies have revealed that gp120 as the major domain contains inducing type specific BNA (PND) and a binding region with CD4 (CD4-BR). PND is located in the hypervariable loop of gp120 (residues 301-336 for a BRU strain), and CD4-BR is in the conservation area (residues 410-450). By using the synthetic fragments from these areas (BRU and MN strains) and HIV-infected persons' sera, the authors established that the immune response to PND and CD4-BR is somewhat interrelated: there is a synchronized response of HIV antibodies to peptides from the two regions in ELISA (r = 0.82). For analysis of this phenomenon, experiments with cross-linked immunoreactivity of rabbit antisera to peptides from PND and CD4-BR with homologous and heterologous peptides were performed by applying three control peptides from HIV and hepatitis B virus. It has been found that there is a cross reactivity between rabbit anti-PND (MN, BRU) and anti-CD4-BR abs. Peptide homological analysis revealed common structural elements for PND and CD4-BR despite significant differences in their proposed functions. There is a large amount of positively charged aa within both PND and CD4-BR which may be involved in gp120-CD4 interaction. Acetylation of Lys residues resulted in complete loss of peptide reactivity. PMID- 1283722 TI - [Expression of HIV-1 tat gene under the control of P 7,5 KD vaccinia virus promoter in CV-1 cells]. AB - The transient expression of the HIV-1 gag genes and a HIV-1 ++trans-activator protein (tat)-encoded was made in cultured CV-1 cells. In recombinant plasmids, the gag gene was under the control of HIV-1 ++trans-activator sequence (tar) and the tat gene was under the control of a 7.5-kd vaccinia promoter. Transactivation of gag gene expression, which was stimulated by a tat gene expression product, was observed in the presence of wild vaccinia virus. The transaction was immunologically evaluated from the binding to monoclonal anti-p17 and anti-p24 antibodies. The findings lead to the discussion whether the regulatory proteins of HIV-1 can express in vaccinia virus vectors. PMID- 1283723 TI - [Study of antigenic structure of HIV-1 protein p24 using monoclonal antibodies]. AB - During the experiments 4 murine and 3 rat hybridomas producing monoclonal antibodies (MAb) against the protein p24 of human immunodeficiency virus type 1 (HIV-1) have been obtained. Using the immunoblotting technique, it was established that all the species of MAb reacted with the same viral proteins which are derivatives of gag gene--p24 and p55. The properties of MAb have been studied in competitive binding. Their ability of binding to different fragments of the gag protein produced by the recombinant plasmids in E. coli cells have been investigated in ELISA. The analysis of the findings suggests that the HIV-1 protein p24 contains at least 3 antigenic epitopes. All species of MAb reacted with 3 different HIV-1 strains and 2 HIV-1 isolates, but failed with 2 different HIV-2 strains. The only MAb NS5E4 can be used as an immunosorbent in the antigenic capture reaction. PMID- 1283724 TI - [Persistent viruses in serological diagnosis of HIV infection]. AB - Specific antibodies to persistent viruses (CMV, EBV, HBV) were detected by ELISA in groups of HIV-infected patients and persons showing indefinite results of the immunoblotting test for HIV-1 antigens, on the one hand, and in HIV-seronegative donors and patients with clinical manifestations of viral infection (CMVI) on the other. The findings indicate that the persons with indefinite immunoblotting test results show elevated blood CMV and HBV antigen levels than in the matched group of seronegative donors. This fact suggests that persistent viral infections might involve in the formation of an indefinite pattern when the sera were tested for HIV. The patients whose sera behaved in such a way represent a clinical risk group for HIV infection and call for further follow-up. PMID- 1283725 TI - [Epidemiology of HIV infection and the organization of anti- epidemiologic measures in the USSR 1987-1991]. PMID- 1283726 TI - The effects of purified 25-kDa lipase from a clinical isolate of Pseudomonas cepacia in the lungs of rats. AB - Nanogram quantities of a 25-kDa lipase purified from culture supernatants of Pseudomonas cepacia 90ee, a sputum isolate from a cystic fibrosis (CF) patient, were placed in the lungs of healthy rats. The resulting pathological changes included large amounts of proteinaceous exudate, the accumulation of polymorphonuclear leukocytes and red blood cells, and disorganization of alveolar structure. Pseudomonas cepacia 90ee immobilized in agar beads was also placed in the lungs of rats in a model of chronic infection. This resulted in bronchopneumonia and a milder inflammatory response than that elicited by the purified enzyme. PMID- 1283727 TI - Electrophoretic analysis of heterogeneous lipopolysaccharides from various strains of Vibrio vulnificus biotypes 1 and 2 by silver staining and immunoblotting. AB - Lipopolysaccharides (LPS) of 11 strains of Vibrio vulnificus biotypes 1 and 2, isolated from an eel farm, and of 10 reference strains, were examined by SDS polyacrylamide gel electrophoresis coupled with silver staining and immunoblotting. LPS samples were obtained from whole-cell lysates, outer membrane fragments, and extracellular products. By silver staining, only a diffuse band of low-molecular weight could be visualized in all cases except for a biotype 1 strain isolated from water. However, immunoblotting with antisera obtained against strains of biotypes 1 and 2 from eels allowed visualization of multiple O polysaccharide chains. All biotype 2 strains, independently of their origins, belonged to the same serotype and presented the same LPS profile, whereas eel isolates of biotype 1 were serologically identical and different from the rest of tested strains of biotype 1. This is the first report of LPSs with a ladder-like structure in Vibrio vulnificus. PMID- 1283728 TI - Differentiation between parasystole and reentry in concealed bigeminy. AB - There are two different theories to explain the mechanism of concealed bigeminy: one is '2:1 concealed reentry'; the other is 'irregular parasystole.' Two exemplary cases of the even-number variant of concealed bigeminy are presented. In case 1, the mechanism can be explained by an irregular parasystole due to a modulated parasystole; however, findings during temporary sinus arrest caused by vagal stimulation indicate that this case is not governed by a parasystole, but by a 2:1 concealed reentry. In case 2, the mechanism can be explained by a 2:1 concealed reentry without parasystole; however, findings during temporary sinus arrest indicate that this case is governed by an irregular parasystole due to a type-I second-degree entrance block. Thus, in cases of concealed bigeminy without pure ectopic cycles, it does not seem easy to explain the mechanism of concealed bigeminy on the theory of a modulated parasystole. PMID- 1283729 TI - An ultrastructural study of the effects of topical tretinoin on microcomedones. AB - It has been hypothesized that topical tretinoin prevents inflammatory acne lesions by loosening follicular impactions (microcomedones) and clearing the follicular canal of retained keratin. To lend support to this hypothesis, 15 volunteers applied 0.1% tretinoin cream once daily for 12 weeks to one side of the face and an emollient cream to the other side. During the 12-week treatment period, samples of microcomedones were obtained using the follicular biopsy technique. By 6 weeks, the number of microcomedones was reduced approximately 50% from baseline on the side treated with tretinoin and approximately 80% at the end of the study. Only a minimal reduction in the number of microcomedones was seen on the emollient side, even after 12 weeks of application. Morphologic examination showed a progressive loss of the cohesiveness of the microcomedones and ultrastructural alterations in the epithelial cells treated with tretinoin. The microcomedones changed from well-developed keratinous plugs containing many bacteria to a few wispy layers of keratin containing few bacteria. This study confirms the microcomedolytic activity of tretinoin and provides evidence that this activity is associated with changes in the differentiation of the follicular epithelial cells. PMID- 1283730 TI - Administration of human recombinant insulin-like growth factor-I to patients following major gastrointestinal surgery. AB - OBJECTIVE: The aim was to study the pharmacokinetic parameters and biological activity of a single dose of human recombinant IGF-I (rhIGF-I) administered to patients following major gastrointestinal surgery. DESIGN: A double blind placebo controlled externally randomized study of 30 patients; the study commencing 24 hours after major colonic or gastric surgery. MEASUREMENTS: After a baseline blood sampling day, IGF-I (40 micrograms/kg by single subcutaneous dose, n = 20) or placebo (n = 10) was administered and serum and urine samples collected over the ensuing 72 hours. Serum IGF-I, IGF-II, IGF binding proteins (IGFBP-1, IGFBP 3), GH and insulin were measured by radioimmunoassay. Serum IGF bioactivity was assessed using a validated porcine cartilage bioassay. Serum and urinary electrolytes were measured by standard methodology. RESULTS: Serum immunoreactive IGF-I levels peaked at 4 hours following injection of IGF-I (1.09 +/- 0.12 U/ml mean +/- SEM), remained elevated for 15 hours and returned to basal levels by 24 hours after injection. IGF bioactivity was increased by 57% 6 hours after IGF-I injection. Mean levels of IGFBP-1 and IGFBP-3, IGF-II and GH were unaffected by IGF-I administration. Insulin levels were suppressed at 30 minutes following injection of IGF-I compared with the placebo group (16.9 +/- 3.0 mU/I vs 32.3 +/- 7.1, P = 0.02); thereafter, there were no differences in insulin levels. The mean change in serum creatinine following IGF-I (-6.3 +/- 3.0 mmol/l) was significantly different from that in the control group (+7.2 +/- 6.2, P = 0.03). Creatinine clearance rose from a mean of 71.6 +/- 7.5 ml/min to 83.2 +/- 7.6 ml/min after IGF-I treatment (P = 0.02). In the IGF treated patients, cholesterol levels consistently fell (-0.20 +/- 0.05 mmol/l); this was not observed in the placebo group (+0.20 +/- 0.14, P = 0.006). Basal serum potassium levels in the IGF treatment group (4.1 +/- 0.1 mmol/l) fell to 3.8 +/- 0.1 at 4 hours (P = 0.002) and 3.6 +/- 0.1 at 10 hours (P = 0.001) returning to a level of 4.0 +/- 0.1 (P = 0.293) at 24 hours after injection. There were no other observed differences in serum or urinary electrolytes or serum free fatty acids and triglycerides. Pharmacokinetic parameters derived from baseline adjusted IGF-I measurements revealed a slow absorption of the administered dose with a Tmax of 5.0 +/- 0.43 hours and an elimination half-life of 10.8 +/- 1.2 hours. The computed volume of distribution was 0.33 +/- 0.05 I/kg and the clearance on average 25 ml/min. CONCLUSION: A single subcutaneous dose of IGF-I normalized circulating IGF-I levels in post-operative patients, was well tolerated and without side-effects. IGF bioactivity was increased and associated with a fall in serum cholesterol, potassium and creatinine levels and a rise in creatinine clearance. Further long-term studies are now required to assess the anabolic effects of rhIGF-I in this type of patient group. PMID- 1283731 TI - Galanin inhibits tolbutamide-stimulated insulin secretion in the perfused pig pancreas. AB - The neuropeptide galanin is known to inhibit insulin secretion in a variety of species. However, controversies exist regarding its action on insulin secretion in the perfused pig pancreas, since both inhibitory and stimulatory effects have been described. We therefore perfused the isolated porcine pancreatico-duodenal block with galanin (100 nmol/l) in the presence of 5 or 15 mmol/l glucose or with 5 mmol/l glucose and 10 mumol/l tolbutamide. We found that at this dose level, galanin did not affect insulin secretion stimulated by glucose alone. In contrast, galanin clearly suppressed tolbutamide-stimulated insulin secretion. Hence, we conclude that galanin has a weak influence on insulin secretion in the pig pancreas, being unable to inhibit glucose-stimulated insulin secretion at the dose level of 100 nmol/l. However, when active, galanin clearly inhibits insulin secretion also in the pig pancreas. PMID- 1283732 TI - Comparison of top and bottom loading of a dextran gradient for rat pancreatic islet purification. AB - Rat pancreatic islet yields obtained with dextran gradient purification were compared after suspending the digest into either the top or the bottom layer of the gradient. A 5-layer discontinuous gradient was used, which consisted of 16 ml 31% dextran as bottom layer, overlayered with 25%, 23%, 20% and 11% dextran (4 ml each). When the digest of 1 rat pancreas was suspended into the top layer of the gradient, the total number of islets obtained from the 11-20, 20-23 and 23-25% interfaces was 862 +/- 38, 240 +/- 39 and 54 +/- 5, respectively. From this gradient, also 1409 +/- 81 islets were retrieved from the bottom layer (i.e., exocrine pellet). In contrast, when the pancreas digest was suspended into the bottom layer of the gradient, 1964 +/- 63, 435 +/- 42, and 177 +/- 34 islets were obtained from the successive interfaces, and only 50 +/- 20 islets from the exocrine pellet. The total islet volume obtained from the two uppermost interfaces was 3.46 +/- 0.31 microliters after top-loading, and 4.93 +/- 0.16 microliters after bottom-loading (n = 7, p < 0.01). When the islets retrieved from one bottom loaded gradient were transplanted into either 1 (n = 6) or 2 (n = 9) diabetic recipients, glucose levels normalized in all instances. We therefore conclude that a bottom-loaded dextran gradient separates islets from exocrine tissue effectively, resulting in significantly higher islet yields than obtained with a top-loaded dextran gradient. PMID- 1283733 TI - Antibacterial properties of investigational, new, and commonly used antibiotics against isolates of Pseudomonas cepacia in Michigan. AB - Microdilution antimicrobial susceptibility testing was performed with 73 isolates of Pseudomonas cepacia collected from the sputum of patients throughout Michigan with cystic fibrosis. Susceptibility testing was done using new and investigational antibiotics (loracarbef, cefixime, cefpirome, desacetyl cefotaxime, cefpodoxime, cefmetazole, cefepime, cefprozil, and fleroxacin) and commonly used antibiotics (ceftazidime, mezlocillin, piperacillin, ciprofloxacin, tobramycin, and amikacin). Ceftazidime was the most active antibiotic, and 91.8% of isolates were susceptible to it with MIC50 and MIC90 values of < or = 4 and 16 micrograms/ml, respectively. For mezlocillin, piperacillin, and ciprofloxacin 84.9, 89 and 39.7% of the isolates, respectively, were mostly moderately susceptible. Loracarbef, cefixime, cefprozil, cefmetazole, cefepime, fleroxacin, cefpodoxime, tobramycin, and amikacin did not show activity against P. cepacia. For cefpirome and desacetylcefotaxime 24.7 and 60.3% of the isolates, respectively, were moderately susceptible. Both MIC50 and MIC90 were > 32 micrograms/ml for cefpirome and 32 and > 64 micrograms/ml for desacetylcefotaxime. PMID- 1283734 TI - Vital dye analysis of cranial neural crest cell migration in the mouse embryo. AB - The spatial and temporal aspects of cranial neural crest cell migration in the mouse are poorly understood because of technical limitations. No reliable cell markers are available and vital staining of embryos in culture has had limited success because they develop normally for only 24 hours. Here, we circumvent these problems by combining vital dye labelling with exo utero embryological techniques. To define better the nature of cranial neural crest cell migration in the mouse embryo, premigratory cranial neural crest cells were labelled by injecting DiI into the amniotic cavity on embryonic day 8. Embryos, allowed to develop an additional 1 to 5 days exo utero in the mother before analysis, showed distinct and characteristic patterns of cranial neural crest cell migration at the different axial levels. Neural crest cells arising at the level of the forebrain migrated ventrally in a contiguous stream through the mesenchyme between the eye and the diencephalon. In the region of the midbrain, the cells migrated ventrolaterally as dispersed cells through the mesenchyme bordered by the lateral surface of the mesencephalon and the ectoderm. At the level of the hindbrain, neural crest cells migrated ventrolaterally in three subectodermal streams that were segmentally distributed. Each stream extended from the dorsal portion of the neural tube into the distal portion of the adjacent branchial arch. The order in which cranial neural crest cells populate their derivatives was determined by labelling embryos at different stages of development. Cranial neural crest cells populated their derivatives in a ventral-to-dorsal order, similar to the pattern observed at trunk levels. In order to confirm and extend the findings obtained with exo utero embryos, DiI (1,1-dioctadecyl-3,3,3',3' tetramethylindo-carbocyanine perchlorate) was applied focally to the neural folds of embryos, which were then cultured for 24 hours. Because the culture technique permitted increased control of the timing and location of the DiI injection, it was possible to determine the duration of cranial neural crest cell emigration from the neural tube. Cranial neural crest cell emigration from the neural folds was completed by the 11-somite stage in the region of the rostral hindbrain, the 14-somite stage in the regions of the midbrain and caudal hindbrain and not until the 16-somite stage in the region of the forebrain. At each level, the time between the earliest and latest neural crest cells to emigrate from the neural tube appeared to be 9 hours.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1283735 TI - Requirement of c-kit for development of intestinal pacemaker system. AB - A discovery that the protooncogene encoding the receptor tyrosine kinase, c-kit, is allelic with the Dominant white spotting (W) locus establishes that c-kit plays a functional role in the development of three cell lineages, melanocyte, germ cell, and hematopoietic cell which are defective in W mutant mice. Recent analyses of c-kit expression in various tissues of mouse, however, have demonstrated that c-kit is expressed in more diverse tissues which are phenotypically normal in W mutant mice. Thus, whether or not c-kit expressed outside the three known cell lineages plays a functional role is one of the important questions needing answering in order to fully elucidate the role of c kit in the development of the mouse. Here, we report that some of the cells in smooth muscle layers of developing intestine express c-kit. Blockade of its function for a few days postnatally by an antagonistic anti-c-kit monoclonal antibody (mAb) results in a severe anomaly of gut movement, which in BALB/c mice produces a lethal paralytic ileus. Physiological analysis indicates that the mechanisms required for the autonomic pacing of contraction in an isolated gut segment are defective in the anti-c-kit mAb-treated mice, W/Wv mice and even W/+ mice. These findings suggest that c-kit plays a crucial role in the development of a component of the pacemaker system that is required for the generation of autonomic gut motility. PMID- 1283736 TI - Caprine beta-mannosidosis: regional differences in deficits of CNS myelin proteins. AB - Caprine beta-mannosidosis is an autosomal recessive disorder characterized by marked deficiency of beta-mannosidase activity, accumulation of oligosaccharides, and pathologic changes involving prominent dysmyelination. The myelin deficits show marked regional variation, with spinal cord mildly affected and many brain regions severely affected by morphologic criteria. In this study, levels of myelin basic protein (MBP) and proteolipid protein (PLP) were measured by immunoblotting in samples prepared from spinal cord, brainstem and cerebral hemispheres of normal and affected goats at 2-4 days (newborns) and 2-4 weeks of age. In affected goats, total levels of MBP in spinal cord were normal, while PLP levels were 60-70% of normal at both ages. In contrast, PLP and MBP in brainstem and cerebral hemispheres were severely decreased at both ages, with levels of PLP 10-13% and MBP 25-29% of normal in newborns, and generally more reduced at 2-4 weeks. When myelin fractions were isolated on 0.32/0.85 M sucrose gradients, yields were about 38 and 25% of normal in spinal cord at the two ages, but less then 3% of normal in brainstem. Yields of myelin-like fraction were decreased as well, but to lesser extents than yields of myelin. Myelin from spinal cord had a normal composition with regard to PLP and MBP content, while the myelin fraction from brainstem was markedly deficient in both proteins. This suggests formation of myelin with a very abnormal composition in brainstem, or inclusion of large amounts of membranes other than myelin in this fraction. The more severe deficits in brainstem and cerebral hemispheres compared to spinal cord are consistent with morphologic observations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283737 TI - A rat monoclonal antibody specific for murine type 1 pneumocytes. AB - A rat monoclonal antibody (MAb), 411-52, that binds specifically to murine pulmonary alveolar type 1 cells was developed. The cell-binding specificity of MAb 411-52 was assessed by light microscopy on immunoperoxidase-labeled tissue sections, electron microscopy on immunogold-labeled tissue blocks, and by flow cytometric analysis and fluorescence-activated cell sorting of immunofluorescently labeled cells enzymatically dissociated from murine lungs. The epitope recognized by MAb 411-52 was first detected in immunoperoxidase stained sections of neonatal lungs of mice approximately 3 weeks after birth. In adult mice, the MAb 411-52-directed, immunoperoxidase-staining pattern was uniform throughout the lung parenchyma, was restricted to the luminal surfaces of alveoli, and was absent from type 2, endothelial, and interstitial cells, as well as from the epithelial cells of conducting airways. Electron microscopic analysis of immunogold-labeled lung tissue confirmed the type 1 cell binding specificity of MAb 411-52. Analysis by multiparameter, laser flow cytometry indicated that MAb 411-52 binds to 4.6 +/- 0.5% (mean +/- SD) of enzymatically dissociated cells from the lungs of normal adult mice. The absence of immunogold-labeling of type 2 cells suggested that the epitope recognized by MAb 411-52 might be a differentiation marker for the type 1 cell phenotype. With this MAb and standard immunohistochemical techniques, it is possible to visualize directly type 1 cells in paraffin sections. PMID- 1283738 TI - The contrast sensitivity function in low vision. AB - The contrast sensitivity of 51 low vision patients (95 eyes) showed a substantial decrease in all spatial frequencies. The peak contrast sensitivity was shifted to 1 C/D from the normal 3-4 C/D. The high-frequency cut off is correlated to the visual acuity positively. Of the 33 patients, the preferred eye was the eye with better peak sensitivity in 28 patients (84%), while the preferred eye was the eye with better visual acuity in 22 patients (66%). It seems that the peak sensitivity is more important than visual acuity in determining eye preference. It provides a useful information for the clinician to determine which eye to train with low vision aids. Forty patients among 46 patients (87%) with RFN (Recognized Frequency Number) > or = 3 are able to read No.5 reading card, while 5 patients among 5 patients with RFN < 3 are not able to read No.5 reading card. The contributions of CSF to the low vision are evaluated. PMID- 1283739 TI - Cloning of a type I keratin from goldfish optic nerve: differential expression of keratins during regeneration. AB - We report the cDNA sequence and predicted amino acid sequence of a novel type I keratin, designated as GK50, and show that keratin expression in the goldfish optic nerve is highly complex. The GK50 protein is one of at least three type I keratins expressed in goldfish optic nerve based on both antibody reactivity and blot-binding to the type II keratin ON3. After optic nerve crush in situ hybridization shows a localized increase in GK50 mRNA expression in the crush zone. This is in contrast to ON3 mRNA which shows a localized increase that is limited to the proximal and distal margins of the crush zone, suggesting a diversity of keratin expression in different cell types of the goldfish optic nerve. PMID- 1283740 TI - Cytokeratin 14 expression in rat liver cells in culture and localization in vivo. AB - Rat liver epithelial cells (LECs) are non-parenchymal proliferating cells that readily emerge in primary culture and can be established as cell lines, but their in vivo cell(s) of origin is unclear. We reported recently some evidence indicating that the LEC line, T51B, contains two cytokeratins (CKs) equivalent to human CK8 and CK14 respectively. T51B cells also contain vimentin assembled as a network of intermediate filaments distinct from that of the CKs. In the present study, we examined the expression of CK14 gene in various LEC preparations and a Triton-resistant rat skin cytoskeletal fraction, and then assessed its usefulness as an LEC specific marker in the liver. Northern and Western blot analyses with cDNAs and antibodies for CK8, CK14, CK18 and vimentin confirmed that rat hepatocytes express CK8 and CK18 genes only, whereas T51B cells express CK8, CK14 and vimentin genes in the absence of CK18. CK14 was also present in LECs derived as primary from embryonic-day 12 rat liver and secondary cultures from 4-day-old rat liver. Primary cultures of oval cells isolated from 3'-methyl-4 dimethylaminoazobenzene (3'-Me-DAB) treated rat liver (an enriched source of biliary epithelial cells) contained CK14 mRNAs which were slightly shorter than those in LECs. The analyses of CK5 (the usual partner of CK14) gene expression using specific cDNA and antibody clearly demonstrated its absence in LECs. In situ double immunolocalization analyses by laser scanning confocal microscopy showed that CK14 was not present in hepatocytes (HES6+ cells) and was expressed in some biliary epithelial (BDS7+ cells). CK14-positive cells were also found in the Glisson's capsule. However, CK14-positive cells of the portal region were vimentin negative, whereas those of the Glisson's capsule were vimentin positive. Our results suggest that CK14 gene expression is part of the differentiation program of two types of LECs and that this differential CK14 gene expression can be used as a new means to type LECs in culture and in vivo. PMID- 1283741 TI - Characterization of an endothelial protein in the developing rabbit kidney. AB - A new protein (EnPo 1 antigen) abundant on endothelial cells and glomerular podocytes has been characterized by means of the mouse monoclonal antibody EnPo 1. Following electrophoretical separation of rabbit kidney homogenates EnPo 1 recognized a protein with a molecular weight of 110 kDa and an isoelectric point of 5.9 in Western blots. Using immunohistological techniques, the EnPo 1 antigen has been localized in high concentrations on glomerular podocytes of different developmental stages. Furthermore, the EnPo 1 antigen was expressed on endothelial cells of all adult rabbit organs tested so far. Detailed analysis of neonatal rabbit kidney revealed the abundance of EnPo 1 antigen on both differentiated vessels as well as on immature endothelial cells and endothelium of the microvasculature. Thus, for the first time a marker for in situ investigations of angiogenic processes within the mammalian kidney is available. Analysis of kidney cryosections by confocal laser scan microscopy revealed a direct connection between mature and differentiating vessels in the outer kidney cortex. Furthermore, two differentially organized cell populations discriminated by their EnPo 1 binding pattern were localized in the embryonic renal cortex. Morphologically, these cells were not distinguishable from other mesenchymal cells. PMID- 1283742 TI - Modification of the in vitro cytotoxicity of hydrogen peroxide by iron complexes. AB - The effect of a range of iron chelates on the cytotoxicity of H2O2 was studied on a mammalian epithelial cell line. Iron complexes which were internalised enhanced the cytotoxicity of H2O2 measured by delayed thymidine incorporation. Iron complexed to 8-hydroxyquinoline (Fe/8-HQ) potentiated the cytotoxicity of 50 microM by 38% and Fe/dextran by 23%. Pre-exposure of cells to Fe/dextran at 4 degrees C did not result in any potentiation of H2O2-induced cytotoxicity which we ascribe to failure of the Fe/dextran to be endocytosed at low temperature. Iron complexes which are slowly taken up or remain extracellular protected the cells from H2O2-induced cytotoxicity. Thus, Fe/EDTA inhibited the cytotoxicity of 50 microM H2O2 by 33%; Fe/ADP by 80% and Fe/ATP by 88%, suggesting mutual extracellular detoxification. PMID- 1283743 TI - Conformational study of a peptide epitope shows large preferences for beta-turn conformations. AB - The conformational preferences of the 7-residue peptide Glu-Val-Val-Pro-His-Lys Lys was investigated using a global search algorithm, namely the Electrostatically Driven Monte Carlo (EDMC) method, and the ECEPP/2 potential energy function. This particular sequence corresponds to the N-terminal portion of a 19-residue peptide antigen whose three dimensional structure, when complexed to a cognate antibody, was reported recently. As a result of this study a series of low-energy conformations were identified showing a common folding pattern with residues Val-3, Pro-4, His-5 and Lys-6 forming a beta turn. A comparison of the computed conformations with the one determined by X-ray crystallography in the antibody-antigen complex reveals marked similarities. In most of the cases rms deviations smaller than 1.1 A were found for the backbone atoms of the four residues forming the turn. These results suggest that the recognition process is accomplished in this case through the interaction of the antibody with relatively stable conformers of the antigenic peptide. PMID- 1283744 TI - [Therapeutic endoscopy today. Implantation of endoprostheses in the upper digestive tract and hepatobiliary system]. PMID- 1283745 TI - [Therapeutic endoscopy today. Laser therapy of the upper and lower digestive tract]. PMID- 1283746 TI - [What is the importance today of determining blood sedimentation rate in addition to measuring so-called acute phase proteins?]. PMID- 1283747 TI - DP epitope mapping by using T-cell clones. AB - To determine whether a correlation exists between the genomic HLA class II DP DNA polymorphism and cell surface expression and to detect the DP epitopes responsible for alloreactivity, anti-DP T-cell clones were generated against new PLT blank RFLP DPa and DPb-defined specificities. The clones were tested on the 10th IHWS B-LCLs and on local panel cells. Oligotyping of the tested cells made it possible to (a) correlate the DPa specificity with the DPB1*0402 specificity and (b) split DPb into DPB1*1001 and DPB1*1401. By comparing DNA sequences of the second exon to panel reactivity, the epitopes responsible for DPB1*1001 and 1401 were defined and attributed to beta-chain residues contributing to peptide selection inside the HLA groove. However, DNA sequences could not explain anti DPa allospecificity, indicating that another structure not yet definable may be involved. PMID- 1283748 TI - Mutagenesis around residue 176 on HLA-B*0702 characterizes multiple distinct epitopes for anti-HLA antibodies. AB - Preformed antibodies against HLA-A,B,C molecules cause hyperacute rejection of transplanted allogeneic tissues. To understand better the molecular basis of hyperacute rejection, narrowly reactive anti-HLA-B*0702 monoclonal antibodies have been studied. Previous epitope mapping studies of these monoclonal antibodies by mutating B*0702 have conflicted with antibody-blocking studies. To resolve these discrepancies, we mutated B*0702 residues around the antigenically important residue 176, and measured anti-B*0702 antibody binding. Antibody MB40.2 binding is abrogated by mutations at residues 169, 180, and 182, close to residue 176 in the primary structure. However, MB40.2 binding is not affected by 12 other B*0702 mutations close to residue 176 in the tertiary structure. This suggests that MB40.2 may recognize a sequential B*0702 epitope including residues between positions 169-182. Antibody BB7.1 binding requires B*0702 alpha 2-domain residues 166 and 169. Competition for B*0702 residue 169 explains why MB40.2 and BB7.1 crossblock. Because BB7.1 binding also requires B*0702 alpha 1-domain residues, BB7.1 may contact both alpha-helices, straddling the B*0702 peptide-binding groove. Previous results showed that both MB40.2 and MB40.3 binding require B*0702 residues 176/178. However, MB40.3 binding is not affected by any of 15 other mutations near residue 176. This suggests that MB40.3 does not contact residues 176/178; rather, residues 176/178 appear to affect MB40.3 binding by subtly influencing B*0702 conformation. Thus, monoclonal antibodies influenced by a defined B*0702 region around residue 176 appear to recognize three different types of epitopes. This suggests that human alloantibodies also recognize diverse types of HLA epitopes. PMID- 1283749 TI - Anticonvulsant alone in the relief of cancer pain. PMID- 1283750 TI - Octreotide in the management of inoperable gastrointestinal obstruction in terminal cancer patients. PMID- 1283751 TI - Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides. AB - Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis. PMID- 1283752 TI - Virus-like particles with reverse transcriptase activity associated with Kawasaki disease. AB - To investigate the etiologic agent associated with Kawasaki disease (KD), we initially established a cocultivation system using concanavalin A (Con A) stimulated lymphoblastoid cells obtained from each retrovirus-seronegative individual's peripheral blood mononuclear cells (MNCs) cocultivated with each of 1) 40 patients with KD, 2) 10 patients with other viral infection and skin rash, and 3) 10 age- and sex-matched normal controls. Five major findings suggested that virus-like particles with reverse transcriptase (RT) activity are associated with KD. First, RT activity appeared significantly higher on day 12 after the onset of fever in the KD patients than in those with other viral infections and normal controls (dTMP incorporation: 3,645 +/- 248 vs. 434 +/- 50 vs. 412 +/- 46 cpm, P < 0.0001). Second, the RT activity was not endogenous, because the Con A stimulated lymphoblastoid cells were obtained from the individuals who were negative for retrovirus. Third, virus-like particles (80-100 nm in diameter) by electron microscopy were found in the concentrated pool supernatants of particulate fraction containing RT activity subjected to sucrose density gradient, obtained from KD patients. Fourth, the viral product, a 31.4 kilodalton molecule, was detected by SDS-PAGE after internal labelling (methionine-S35) and density gradient centrifugation. Fifth, using a "retrovirus universal pol gene region" as a primer and the RT-PCR method, a retrovirus-specific band was detected in the cocultivated supernatants obtained from four KD and one AIDS patients but not in patients with rubella or in healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283753 TI - Serum hepatitis C virus (HCV)-RNA and response to alpha-interferon in anti-HCV positive chronic hepatitis. AB - Hepatitis C virus (HCV) replication was assessed before and during alpha interferon (IFN) treatment in 22 anti-HCV positive patients with posttransfusion or sporadic chronic hepatitis (CH). Eleven patients were "responders" and 11 patients "non-responders" to IFN. Thirteen anti-HCV negative healthy subjects and five anti-HCV negative patients with autoimmune CH served as controls. Serum HCV RNA was detected by the polymerase chain reaction (PCR) in all untreated anti-HCV positive patients but in none of the anti-HCV negative subjects. PCR primers from the 5'-noncoding (NC) region were more sensitive than primers from a non structural (NS5) region in detecting HCV-RNA (21/22, 95% vs. 7/22, 32%, respectively). Positive strand HCV-RNA titre and positivity rate for the negative strand were similar in responders and non-responders before IFN treatment, as well as anti-c100-3 titre by enzyme-linked immunosorbent assay (ELISA), and anti 5-1-1, anti-c33c, anti-c22 positivity rate by immunoblot assay (RIBA). HCV-RNA positivity by both NC and NS primers was more frequent before IFN among responders. During IFN treatment, serum HCV-RNA was detectable, mostly at low titres, in 1 (NC positive) of the 11 responders and in 9 (4 NS positive and 5 NC positive) of the 11 non-responders. Among the four non-responders who were NS positive during IFN, three were NC positive before IFN. Serum HCV-RNA was always found in our post-transfusion or sporadic anti-HCV positive patients with CH. Viraemia generally decreased during IFN treatment, but no available HCV markers clearly distinguished responders from non-responders before IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283754 TI - Expression of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein in normal salivary glands and primary salivary gland tumors. AB - The distribution of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein was studied in 38 primary salivary gland tumors. S 100 protein, a useful marker of myoepithelial cells, was demonstrated in some benign tumors. Carcinoembryonic antigen expression was consistently positive in adenoid cystic carcinoma. Demonstration of epithelial membrane antigen helped to confirm the epithelial nature of some neoplastic cells. Alpha fetoprotein was not expressed in any of the cases examined. No correlation was found between immunopositivity and tumor behavior in the present series. PMID- 1283755 TI - Electrophoretic detection of salivary alpha-amylase activity. AB - Fresh samples of human whole saliva containing approximately 20-40 micrograms protein were analyzed using SDS-polyacrylamide slab gel electrophoresis systems. More than 20 protein bands were revealed by Coomassie Brilliant Blue R 250 staining. Some of the protein bands were shown to be glycoprotein-positive with PAS (periodic acid-Schiff) reagent. The protein bands with alpha-Amylase activity appeared within a molecular weight range of 120,000-180,000, which is 2 to 2.8 times higher than the normal molecular weight reported for alpha-Amylase from parotid saliva, and showed positive staining with PAS reagent. These results show that the alpha-Amylase in whole saliva appears to exist in a macromolecular form which is not dissociated in the presence of sodium dodecyl sulfate (SDS). PMID- 1283756 TI - Insecticide poisoning in pregnancy. A case report. AB - A 25-year-old multigravida drank an organochlorine insecticide in an attempt to commit suicide at 16 weeks of pregnancy. This resulted in the death of twin fetuses and vaginal bleeding. The pregnancy was terminated using gemeprost, syntocinon and later surgical evacuation of the uterus. She developed respiratory arrest after the fetuses were aborted and also after surgical evacuation. On both occasions, she was intubated and mechanically ventilated. We believe that organochlorine insecticides may be fetocidal. In addition, surges in blood levels may occur during termination of pregnancy, delivery or evacuation of retained products of conception. PMID- 1283757 TI - [Assessment of air pollution health effects on respiratory organs]. AB - During the past three decades, industrial expansion in Japan has been remarkable, resulting in a numerous number of chemical substances got synthesized. Unfortunately, our living environment has concomitantly been polluted with such substances released through industrial activities and our daily lives, and health injuries have occasionally occurred in the human population. Although the critical conditions in the 1960s were overcome by the countermeasures we took, the potential for environmental pollution still remains. In the present social and economical situation, the management of environmental pollutants should be decided depending upon more quantitative and predictive evaluation of their health effects. In this paper the author tries to evaluate the relation of air pollution to chronic bronchitis, bronchial asthma and pulmonary cancer from a quantitative point of view. PMID- 1283758 TI - Role of cyclic AMP in prostaglandin-induced modulation of acetylcholine release from the myenteric plexus of guinea pig ileum. AB - Prostaglandins (PGs) have modulatory effects on spontaneous and nicotine-induced release of acetylcholine (ACh) from the myenteric plexus of guinea pig ileum. To determine whether cyclic AMP is involved in the mechanisms of these effects, we studied ACh release under conditions that inhibit PG synthesis. Indomethacin (IND), a cyclooxygenase inhibitor, inhibited ACh release concentration dependently. The effect of the maximally inhibitory concentration of IND (2.8 microM) on nicotine-induced ACh release were reversed concentration-dependently by PGE2, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and 8-bromo cyclic AMP. These compounds caused concentration-dependent reversal of the inhibition of spontaneous ACh release by IND, but their concentrations for restoration of spontaneous release were higher than those for restoration of nicotine-induced release. The effects of PGE2 and forskolin or IBMX were not additive in reversing the inhibition of nicotine-induced ACh release by IND. Neither forskolin nor 8 bromo cyclic AMP alone had any significant effect on either release. These results showed that increase in the level of cyclic AMP in myenteric cholinergic neurons restored ACh release from the tissue whose PG level had been lowered by IND and indicated that endogenous PGs may modulate the level of intraneuronal cyclic AMP. PMID- 1283759 TI - [Chronic obstructive lung disease: does accompanying arrhythmia have any clinical significance?]. AB - Clinical significance of cardiac arrhythmias in patients with advanced and stable chronic obstructive pulmonary disease was assessed 22-24 hour Holter monitoring revealed supraventricular and ventricular arrhythmias in all 65 patients. There was a great variation of arrhythmia quality and quantity in the study group. Among others, 1808 complex ventricular extrasystoles in 33 patients and 302 episodes of nonsustained ventricular tachycardia in 19 patients were recorded. No sustained symptomatic ventricular arrhythmias were observed. We found no correlation between the intensity of ventricular and supraventricular extrasystoles and clinical parameters as assessed by echocardiography, spirometry and gasometry. However, patients with complex ventricular arrhythmias had larger right ventricular diameter in echocardiography. Of 65 studied patients, 14 (21%) died during follow-up ranging from 1 month to 3.2 years, mean 12.2 months. Two outpatients died suddenly. These 14 patients had larger right ventricle and left atrial dimension, more pronounced PaO2 decrease as well as lowered FEV1 as compared to the survivors. No differences in the incidence of cardiac arrhythmias were noted. Summarizing, despite the great prevalence of cardiac arrhythmias in patients with advanced stable COPD we found no life-threatening ventricular arrhythmias during approximately 1500 hours of holter monitoring. Cardiac arrhythmias seem not to influence the prognosis in these patients. PMID- 1283760 TI - [Extra-parasystole, "jumping" contractions and their concurrence with the Wolff Parkinson-White syndrome]. PMID- 1283761 TI - Introduction: the metabolic cardiovascular syndrome. AB - During the last few years new knowledge concerning risk factors for cardiovascular diseases (CVD) has emerged. Many of these are metabolically interrelated. The clustering of a variety of metabolic disorders in individuals prone to develop CVD has led to the launching of the so-called metabolic cardiovascular syndrome (MCVS). At the XIIIth Scandinavian Congress of Cardiology in Oslo, Norway, on June 1991, a satellite symposium was arranged on the MCVS. The present supplement comprises articles written by the symposium speakers, who are all experts in various fields of relevance to the MCVS. In addition, Per Bjorntorp, Stevo Julius, and Arne Westheim were invited to contribute articles to make the coverage of the topic more complete. The present introduction summarizes some of the clinical and biochemical features characteristic of the MCVS, with a special reference to the multiplicity of biochemical changes. The possibilities for at least three basic disorders being of primary or causal importance in different individuals are stressed. These are chronic sympathetic overactivity, insulin resistance, and central or visceral obesity. By including the related changes in the hemostatic systems with "hypercoagulability" and "hypofibrinolysis," whereby the importance of thrombosis for the clinically often dramatic complications of the MCVS is stressed, the more specific name atherothrombogenic syndrome (ATS) has been proposed. The non-pharmacological treatment of the syndrome with low-caloric diet and physical exercise is emphasized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283762 TI - The metabolic cardiovascular syndrome. Satellite to the XIIIth Scandinavian Congress of Cardiology. Oslo, Norway, June 5, 1991. Proceedings. PMID- 1283763 TI - Carbohydrate metabolism, insulin resistance, and metabolic cardiovascular syndrome. AB - Insulin resistance is seen in several pathophysiological conditions, such as obesity, diabetes mellitus, and essential hypertension. This means that a greater than normal amount of insulin is needed to give a normal biological response. A major biochemical defect in insulin resistance seems to be a defect in the intracellular nonoxidative metabolism of glucose in muscle cells. However, in many individuals, there is also increased hepatic glucose output. The result of insulin resistance in individuals with normal insulin-secreting capacity is hyperinsulinemia, a potential risk factor for cardiovascular disease. PMID- 1283764 TI - Hypertension and the metabolic cardiovascular syndrome: special reference to premenopausal women. AB - It has been proposed that hyperinsulinemia may not constitute a cardiovascular risk in women, and that the metabolic risk profile is less apparent in women than in men. In two different studies, we have assessed the interrelationship between classical coronary risk factors in women with untreated essential hypertension and looked for possible hypertensive-normotensive differences. Hypertensive women (HT1, 156 +/- 2/98 +/- 1 mm Hg, n = 18) in study I turned out to be overweight and had nearly three times higher fasting serum insulin levels than the normotensive control subjects (NT1, 118 +/- 3/77 +/- 2 mm Hg, n = 9). HT1 women with a body mass index (BMI) above 25 kg/m2 had significant higher insulin levels than HT1 women with a BMI less than 25 kg/m2, and when adjusting for BMI the hypertensive-normotensive difference in insulin levels was lost. In HT1 women, the serum insulin level correlated positively to the BMI and triglycerides. In study II, insulin was positively associated with the systolic blood pressure in HTII women (150 +/- 3/99 +/- 1 mm Hg, n = 29), and a negative correlation appeared between the glucose/insulin ratio and the systolic as well as diastolic blood pressure. No difference was observed in BMI and insulin between HTII and NTII women (121 +/- 3/79 +/- 1 mm Hg, n = 18). In HTII women, plasminogen activator inhibitor (PAI-1) levels were higher and the euglobulin clot lysis time prolonged compared to NTII women. PAI-1 was positively correlated to insulin and triglycerides and negatively to high-density lipoprotein (HDL) cholesterol in HTII women. Strong associations between potential cardiovascular risk factors seem to be present even in untreated women with mild hypertension, with insulin being correlated to hypertension, BMI, fibrinolytic activity, triglycerides, and HDL cholesterol. PMID- 1283765 TI - Lipoproteins, lipases, and the metabolic cardiovascular syndrome. AB - High levels of plasma triglycerides and very-low-density lipoproteins and low levels of high-density lipoproteins are consistently found in the metabolic cardiovascular syndrome. These changes are exaggerated postprandially. In the liver, synthesis and secretion of triglyceride-rich particles are increased. In addition, the removal capacity of plasma triglycerides is decreased, due to downregulation of lipoprotein lipase in skeletal muscles by hyperinsulinemia. Resistance to insulin-stimulated glucose uptake is believed to be the main pathogenetic factor. However, increased flux of free fatty acids from abdominally localized adipose tissue must also be considered when discussing pathogenesis. Treatment is primarily nonpharmacological, with diet and increased physical activity. PMID- 1283766 TI - Abdominal fat distribution and the metabolic syndrome. AB - Recent studies have indicated that the waist/hip circumference ratio (WHR), an index of abdominal fat distribution, is a risk factor for cardiovascular disease and diabetes, in parallel with other previously established risk factors. Obesity, without taking fat distribution into account, seems to be associated with WHR in its relationship to the metabolic risk factors for these diseases. The important component of the WHR is probably the mass of visceral fat. This cluster of phenomena constitute what has recently been called the metabolic syndrome or syndrome X. Visceral fat mass is probably increased by a multiple endocrine aberration, where steroid hormones are important. This seems to cause insulin resistance by direct effects on the periphery, which may be amplified by the metabolism of the enlarged visceral adipose tissues. PMID- 1283767 TI - Hypercoagulability and reduced fibrinolysis in hyperlipidemia: relationship to the metabolic cardiovascular syndrome. AB - Hypercholesterolemia is seen as an important risk factor for coronary artery disease (CAD), as the incidence of CAD is strongly correlated with the level of serum cholesterol in epidemiological studies. However, hypercoagulability and reduced fibrinolytic capacity, often seen in survivors of myocardial infarction, are associated with hypertriglyceridemia (possibly concomitant with low levels of high-density lipoprotein cholesterol) and not with increased levels of total or low-density lipoprotein cholesterol. The important role of thrombogenesis in CAD is supported by the fact that initial high levels of plasma fibrinogen, coagulation factor VII (VIIc), and plasminogen activator inhibitor (PAI-1) are all independent risk factors for CAD or recurrent myocardial infarction as found in multivariate analyses of epidemiological studies. Furthermore, high plasma levels of VIIc and PAI-1 are associated with hypertriglyceridemia, reduced glucose tolerance, overweight, and hyperinsulinemia. The contribution of thrombogenic risk factors to the metabolic cardiovascular syndrome (MCVS) is thus established. Diet intervention is preferable for the normalization of hypercoagulability and hypofibrinolysis associated with MCVS. In familial combined hyperlipidemia, however, and especially with concomitant thromboembolic disease, diet alone is often not sufficient, and drug treatment with anticoagulants and/or lipid-lowering drugs may be necessary. PMID- 1283768 TI - The sympathetic nervous system may modulate the metabolic cardiovascular syndrome in essential hypertension. AB - The association between blood pressure and coronary artery disease may be caused by a concurrence of atherogenic biochemical abnormalities in hypertensive patients, i.e., the metabolic cardiovascular syndrome (increased total cholesterol, triglycerides, and insulin; decreased high-density lipoprotein (HDL) cholesterol; and insulin resistance, glucose intolerance, and blood platelet dysfunction). There are numerous reports of sympathetic nervous system overactivity in hypertensive subjects that could be of importance for the pathophysiology of the high blood pressure. Plasma catecholamines have metabolic hormonal effects at concentrations slightly above low normal resting levels. Even transiently and certainly chronically raised plasma catecholamine levels may cause biochemical abnormalities. Catecholamines may raise total cholesterol, triglycerides, and insulin, decrease HDL cholesterol, and cause insulin resistance and glucose intolerance, and recent evidence supports an in vivo influence of epinephrine on blood platelets, causing dysfunction in hypertensive subjects. Thus, the sympathetic nervous system may modulate the metabolic cardiovascular syndrome in essential hypertension. Hypertensive subjects may respond to environmental stimuli with larger sympathoadrenal responses than normal subjects. Furthermore, emotional stress has been associated with coronary artery disease. Thus, the metabolic hormonal effects of catecholamines, by causing the metabolic cardiovascular syndrome, may be the crucial link between "stress" and cardiovascular disease. PMID- 1283769 TI - Early association of sympathetic overactivity, hypertension, insulin resistance, and coronary risk. AB - Whereas this review is based on the available evidence, interpretation of the data is entirely hypothetical and subjective. To a large degree the review reflects our long-standing fascination with the role of the sympathetic overactivity in hypertension. The basic tenet is that sympathetic overactivity in hypertension may lead to a number of secondary changes, all of which are conductive to coronary heart disease. We also propose that insulin resistance and hypertension are associated through an underlying hemodynamic abnormality and again find good evidence for a possible role of sympathetics in the genesis of such hemodynamic changes. Future research in our laboratory will be oriented toward experimental testing of various aspects of the proposed sympathetic overactivity/hypertension/insulin resistance hypothesis. PMID- 1283770 TI - Physical activity and the metabolic cardiovascular syndrome. AB - Hyperinsulinemia, lipid abnormalities, and impaired fibrinolytic capacity may accompany hypertension, and comprise the metabolic cardiovascular syndrome. They are all independent risk factors for coronary artery disease. Lifestyle modifications can reduce the coronary artery risk. Physical activity has been shown to improve insulin sensitivity, reduce hypertriglyceridemia, improve fibrinolytic capacity, and reduce the blood pressure. A sedentary lifestyle is associated with increased mortality compared to a physically active lifestyle. Hypertensive patients, who often have other atherothrombogenic risk factors, should be encouraged to undertake physical activity as an adjuvant to other nonpharmacological interventions as well as to pharmacological treatment. PMID- 1283771 TI - The metabolic cardiovascular syndrome: syndrome X, Reaven's syndrome, insulin resistance syndrome, atherothrombogenic syndrome. AB - A short review of the metabolic cardiovascular risk syndrome (MCVS) is given. Traditionally, cardiovascular risk has been associated with three so-called "main" risk factors; hypercholesterolemia, hypertension, and smoking. In addition, the association between diabetes and cardiovascular disease has been known for many years in clinical medicine. Primarily, these risk factors have been regarded separately as independent factors, although epidemiological studies showed intercorrelations between them. However, it is now well accepted that relatively few at-risk individuals have only one risk factor, and in many cases a whole "symphony" of factors play together to create what we might call an individuals' risk profile. As an example, very often essential hypertension has been regarded as a disease in itself, which can be successfully treated just by lowering the blood pressure by drugs. When such a strategy obviously failed, the association of elevated blood pressure with dyslipoproteinemia and impaired glucose tolerance attracted more attention, particularly when it was realized that many antihypertensive drugs affected risk in MCVS in a possible negative way. The most important etiologic factor of MCVS is (besides genetics) an excessive caloric intake compared to what the individual spends in physical activity. In the clinical setting, the most important findings of MCVS are central obesity, dyslipoproteinemia with low high-density lipoprotein (HDL) cholesterol, hypertension, reduced insulin sensitivity in peripheral tissues, and increased thrombogenicity. The reduced insulin sensitivity leads to a compensatory increase in beta-cell insulin production, and thereby hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283772 TI - Effects of intracerebral iloprost injections on motor activity and chemically induced seizures in rats. AB - The effects of iloprost, a chemically stable analog of prostacyclin, on motor activity, pentylenetetrazol (PTZ)- and strychnine (ST)-induced seizures were studied in rats. Depression on motor activity was observed after a 500 ng/icv dose. Thus, both spontaneous locomotor activity and exploratory behavior were significantly reduced. While iloprost was ineffective against ST-induced seizures, it produced dose-dependent inhibition of PTZ-induced seizures. ED50 (95% confidence limits) value of iloprost for the suppression of clonic convulsions induced by PTZ was 224.96 (100.43-504.00) ng/icv. Anticonvulsive effect of iloprost was significantly potentiated by clonazepam pretreatment. In this case ED50 of iloprost was 39.40 (23.88-65.01) ng/icv. Unilateral iloprost injections into substantia nigra pars reticulata in a relatively lower dose range (0.5-2.0 ng/ic) also dose-dependently inhibited PTZ-induced seizures. In comparison to other prostanoids iloprost seems to have more potent and selective anticonvulsive activity against PTZ-induced seizures without marked motor depressant action in rats. It is further suggested that antiseizure effect of iloprost might be mediated by GABAergic inhibitory mechanisms. PMID- 1283773 TI - Identification of Oklahoma isolate as a strain of Pseudomonas pseudomallei. AB - Based on the morphological, physiological, biochemical and nutritional characteristics, cellular fatty acid and lipid composition, ubiquinone-8 as the major respiratory quinone, guanine-plus-cytosine content of DNA, DNA-DNA homology value, and sequence alignment of 16S rRNA nucleotides, Oklahoma isolate was reidentified as a strain of Pseudomonas pseudomallei. PMID- 1283774 TI - Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. AB - Based on the 16S rRNA sequences, DNA-DNA homology values, cellular lipid and fatty acid composition, and phenotypic characteristics, a new genus Burkholderia is proposed for the RNA homology group II of genus Pseudomonas. Seven species in this group were transferred to the new genus. Thus seven new combinations, Burkholderia cepacia (Palleroni and Holmes 1981), Burkholderia mallei (Zopf 1885), Burkholderia pseudomallei (Whitmore 1913), Burkholderia caryophylli (Burkholder 1942), Burkholderia gladioli (Severini 1913), Burkholderia pickettii (Ralston et al 1973) and Burkholderia solanacearum (Smith 1896) were proposed. PMID- 1283775 TI - [Enzyme immunoassay stability of alpha tumor necrosis factor in plasma and serum]. AB - With an enzyme immunoassay (ELISA) the stability of tumor necrosis factor alpha (TNF-alpha) has been determined in serum and plasma with and without addition of a protease inhibitor (Aprotinin, Trasylol) 24 hours, as well as seven days after blood collection. It has been observed, that after blood collection the concentration of TNF-alpha decreases first and increases again six hours, (+4 degrees C) respectively twelve hours (-20 degrees C) later. Reasons for that might be: The active form of TNF-alpha is a trimer, the presence of TNF-binding proteins, the presence of TNF-antibodies. Furthermore it has been found, that TNF alpha has the highest stability in plasma at -20 degrees C and -70 degrees C. The addition of Aprotinin had no significant influence on the stability. PMID- 1283777 TI - [Correlation between labeling index by proliferating cell nuclear antigen (PCNA) staining and growth rate in nude mice: preliminary report]. PMID- 1283776 TI - [The cellular and lysosomal fragility of pancreatic acinar cells after ligation of pancreatico-biliary duct in the rat and the protective effects of nafamostat mesilate]. AB - To explore the changes of exorine pancreas in the early stage after ligation of pancreatico-biliary duct (PBD) in rat, we evaluated the changes of serum amylase levels, pancreatic water content as well as the changes of subcellular distribution of cathepsin B in the acinar cells. We also evaluated the lactic dehydrogenase (LDH) discharge from dispersed acini as an index of cellular fragility and cathepsin B leakage from lysosomes as an index lysosomal fragility in vitro study as well as the protective effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT 175) in this model. After ligation of PBD, the serum amylase levels and pancreatic water content, increased significantly compared with those of the control group, but returning to the normal levels at 18 hours. The redistribution of cathepsin B in acinar cells was found and both the cellular and lysosomal fragility increased significantly compared with those of the control groups, shown their peak changes at 12 hours after ligation of PBD. But continuous intravenous administration of FUT 175 (2mg/mg.hr) remarkably attenuated all the parameters. These results indicate the important roles of lysosomal enzyme and lysosomal fragility in the pathogenesis of acute pancreatic injuries in this modes, and the clinical usefulness of FUT 175 in the treatment acute pancreatitis. PMID- 1283778 TI - [Histamine decrease the permeability of an endothelial cell monolayer to dextran: preliminary report]. PMID- 1283779 TI - G-protein mediating the slow depolarization induced by FMRFamide in the ganglion cells of Aplysia. AB - Application of FMRFamide (Phe-Met-Arg-Phe-NH2) induced a slow depolarization in neurons of the Aplysia abdominal ganglion. In voltage-clamped cells, FMRFamide induced a slow inward current that increased when the membrane was depolarized beyond -85 mV, showing a negative slope conductance. However, this inward current never reversed to outward current when hyperpolarized beyond the equilibrium potential for K+. The FMRFamide-induced response was markedly augmented in Ca(2+) free media, but depressed in Na(+)-free media. It was unaffected by a change in external potassium. Intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) significantly depressed the FMRFamide response in a dose-dependent way. Injection of cholera toxin (CTX) which did not cause any current response, selectively and irreversibly blocked the FMRFamide response. Neither 3' deoxyadenosine, an inhibitor of adenylate cyclase, nor H-8, an inhibitor of cyclic adenosine 3',5'-monophosphate (cyclic AMP)-dependent kinase, depressed the FMRFamide response. 3-Isobutyl-1-methylxanthine (IBMX) did not augment the FMRFamide response appreciably. The FMRFamide response was not occluded at all by a relatively large injection of 8-bromo-cyclic AMP. It was concluded that the FMRFamide response is produced by the opening of the voltage-dependent Na(+) channels via activation of a certain CTX-sensitive G-protein which is different from conventional "Gs" that activates adenylate cyclase. PMID- 1283780 TI - Enzymatic inactivation of tachykinin neurotransmitters in the isolated spinal cord of the newborn rat. AB - A mixture of peptidase inhibitors increased the magnitude of the saphenous nerve evoked slow depolarization of a lumbar ventral root and prolonged the similarly evoked inhibition of monosynaptic reflex (MSR) in the isolated spinal cord of the newborn rat in the presence of naloxone. The saphenous nerve-evoked MSR inhibition was curtailed by a tachykinin antagonist, GR71251, and after the treatment with GR71251, the peptidase inhibitor mixture no more prolonged the MSR inhibition. The present results suggest that enzymatic degradation plays a role in the termination of action of tachykinins released from primary afferents in the newborn rat spinal cord. The results provide a further support for the notion that tachykinins serve as neurotransmitters in the spinal cord of the newborn rat. PMID- 1283781 TI - Synovial sarcoma: a new approach to the histological classification and a comparison with malignant mesothelioma. Immunohistochemical study with anti mesothelial cell serum. AB - Routine paraffin-embedded sections from synovial sarcomas in 70 patients were stained immunohistochemically with monoclonal anti-cytokeratin antibody and serum against mesothelial cells. Positive reactions occurred in the epithelioid cells of biphasic tumors only. On the ground of the reaction with anti-mesothelial serum a hypothetical scheme of cell differentiation in synovial sarcoma was set up. PMID- 1283782 TI - Aspiration biopsy of the breast tumors. Analysis of diagnostically difficult cases. AB - In this paper the authors described those of the breast fine needle aspirates which were difficult for interpretation e.g. clear-cut differentiation between benign and malignant character of the lesion could not be made. There were 40 such cases (1.96%) out of 2332 breast tumors biopsied between 1987-1989. In the cases that proved to be malignant on histology the authors described cytological features which speak in favour of malignancy. In the group of smears which proved to be benign on histology the authors described the features that imitate atypia and should not be misdiagnosed as malignant. The described criteria may be of some help in cytological diagnosis of breast masses. PMID- 1283783 TI - Acute myelosclerosis--morphological and clinical analysis of the case. A review of literature. AB - A rare case of acute myelosclerosis has been described in a 20-year-old man. Based upon literature data and our own studies a clinical and morphological analysis of the case was presented. The pathogenesis of the disease was also discussed. PMID- 1283784 TI - Atypical (mild) forms of dihydropteridine reductase deficiency: neurochemical evaluation and mutation detection. AB - We investigated two patients with an atypical (mild) form of dihydropteridine reductase (DHPR) deficiency. Both responded to the loading test with tetrahydrobiopterin; their plasma phenylalanine levels were lowered from 278 mumol/L to 85 and 48 mumol/L and from 460 mumol/L to 97 and 36 mumol/L after 4 and 8 h, respectively. In one of the patients, a combined loading test with phenylalanine followed by tetrahydrobiopterin was also carried out and showed a profile typical for DHPR deficiency. The phenylalanine hydroxylation rate was calculated to be 43 and 87%, 4 and 8 h after cofactor administration, respectively. Diagnosis was confirmed by the absence of DHPR activity in the patient's erythrocytes. In cultured fibroblasts, residual activity of 4 and 10%, respectively, was found. Excretion of urinary pterins was essentially normal, and the biopterin to neopterin ratio in cerebrospinal fluid was increased. Although in both patients cerebrospinal fluid homovanillic acid was found to be normal, and 5-hydroxyindoleacetic acid was substantially reduced, there was no sign of neurologic alterations until the age of 2 y. However, one of the patients recently developed deceleration of head growth, whereas psychomotor development continued to be normal for age. Using the chemical cleavage method on the amplified cDNA, mismatches of T to G at nucleotide 659 and of G to A at nucleotide 475, respectively, were identified. These results also demonstrate that screening for tetrahydrobiopterin deficiency by urinary pterin analysis alone can miss some newborns with mild DHPR deficiency and that all children with tetrahydrobiopterin defects need full neurochemical evaluation together with analysis of the enzyme activity. PMID- 1283785 TI - [Rhabdoid tumor of the neck]. AB - Three pediatric cases of malignant rhabdoid tumor of the neck are described. Clinical data and imaging findings (US, CT and MRI) are stressed. The mass was well defined, containing punctate calcifications in two cases and encasing the vessels in two other cases. Two patients were treated with a chemotherapy regimen according to MMT 89 SIOP protocol, one had chemotherapy and radiotherapy. Two children died of progressive disease; the remaining child who had complete surgical removal of the tumor is on remission 17 months after diagnosis. PMID- 1283786 TI - Prenatal detection of 45,X/46,XX/47,XXX mosaicism through amniocentesis: mosaicism confirmed in cord blood, amnion, and chorion. AB - Sex chromosome mosaicism in amniotic fluid cells poses a serious dilemma in prenatal diagnosis. Chromosome analysis of 56 primary clones of amniocytes revealed three distinct cell lines. Nine cells (16.1 per cent) demonstrated a 45,X karyotype, 11 cells (19.6 per cent) a 47,XXX karyotype, and the remaining 36 cells (64.3 per cent) had a modal number of 46 chromosomes (46,XX). Cytogenetic evaluation of 100 cells from cord blood, amnion, and chorion following delivery confirmed this triple mosaicism. However, the distribution of the three karyotypes in the pre- and postnatal samples was not found in the same proportions. The cord blood had the most similar frequency to that of the amniotic fluid sample, while the chorion had a significantly increased frequency of 47,XXX cells (41 per cent) and a decreased frequency of 45,X cells (2 per cent). Physical examination of the infant at birth revealed no discernible phenotypic abnormalities. Parental karyotypes were normal. This case highlights the difficulty in determining whether a prenatally detected abnormality will be associated with postnatal phenotypic deviation. PMID- 1283787 TI - Non-radioactive assay of AFP, hCG, and uE3 from dried blood specimens: a low-cost alternative for maternal screening for trisomy 21. PMID- 1283788 TI - Ion involvement in memory formation: the potential role of astrocytes. PMID- 1283789 TI - The role of polyphosphoinositides in agonist-evoked release of vasoactive factors from astrocytes. PMID- 1283790 TI - Hepatic encephalopathy: a disorder in glial-neuronal communication. PMID- 1283791 TI - Effects of monoamine transmitters on neurons and astrocytes: correlation between energy metabolism and intracellular messengers. PMID- 1283792 TI - Role of astrocytes in ionic and volume homeostasis in spinal cord during development and injury. PMID- 1283793 TI - Vitronectin modulates glycosaminoglycan dependent reactions of protein C inhibitor. AB - Protein C inhibitor (PCI), a glycosaminoglycan (GAG) dependent serine protease inhibitor, inhibits its target proteases by forming SDS-stable 1:1 complexes. GAGs alter target enzyme specificity of PCI in such a way that e.g. urokinase (uPA) is the preferred target enzyme in the presence of GAGs while in their absence preferentially tissue kallikrein (TK) complexes are formed. The effect of the GAG-binding adhesive glycoprotein vitronectin (Vn) on the GAG-stimulated inhibition of uPA by PCI was studied using an amidolytic assay. In the presence of heparin, Vn protected uPA from inhibition by PCI in a dose-dependent manner with respect to both, Vn- and heparin-concentration. Vn also was active when heparin was replaced by low-molecular weight heparin or heparan sulfate, respectively. In the absence of GAGs, Vn had no effect on the inhibition of uPA by PCI. In a similar system, Vn was far less effective in modifying the inhibitory function of heparin on the inhibition of TK by PCI. When equimolar concentrations of radiolabelled uPA and TK were incubated with PCI in the presence of heparin, only complexes of PCI with uPA were detectable. Addition of Vn reduced this complex formation, whereas, in contrast, complexes of PCI and TK appeared. These results indicate that Vn modulates both, the activity and specificity of PCI and suggest different structural heparin-requirements for the PCI/uPA versus PCI/TK interaction. PMID- 1283794 TI - A new staining technique for the identification of Cryptosporidium oocysts in faecal smears. PMID- 1283795 TI - Embryotoxicity and neurotoxicity in rats associated with prenatal exposure to DURSBAN. AB - DURSBAN (DB; active ingredient chlorpyrifos) is a widely-used organophosphate insecticide. The teratogenic and neurotoxic potential of DB was evaluated in rats in utero by exposing embryos on days 0-7 or days 7-21 of development. These prenatal exposures to DB (0.03, 0.1 or 0.3 mg chlorpyrifos/kg, ip) induced physical abnormalities and embryotoxicity. Rat pups which had been exposed to 0.3 mg chlorpyrifos/kg prenatally demonstrated significant behavioral neurotoxicity on postnatal day 16 in the rotorod test compared to time-matched saline-infused litters. Exposure to DB on postnatal day 3, 10 or 12 also caused neurotoxicity as evaluated by the rotorod test. Our studies suggest prenatal exposure to relatively low concentrations of DB may be associated with embryotoxicity, fetal lethality and behavioral neurotoxicity. PMID- 1283796 TI - Effects of acute ethanol administration on regional serotonin turnover. AB - Numerous studies show the role of biogenic amines in the effects of ethanol. The present work analyzed the effect of an acute sedative-hypnotic dose of ethanol (4 g/kg) on the levels of tryptophan, serotonin (5-HT) and 5-hydroxyindol-acetic acid (5-HIAA), the serotonin synthesis rate and the 5-HIAA elimination rate in several regions of the brain. The 5-HT synthesis rate was not enhanced by ethanol administration, despite increases in brain tryptophan, 5-HT and 5-HIAA, which were primarily in the medulla-pons. The increased indole levels could be due to inhibition of 5-HIAA elimination from the brain. PMID- 1283797 TI - [Sudeck's disease]. AB - The treatment of Sudeck's atrophy is not easy since there is a constant risk of relapse into the inflammatory stage. The earlier the diagnosis is established, the higher is the likelihood that treatment will be successful. As a rule, dystrophic lapses can be avoided by the use of prophylactic measures, even in patients at risk. Here, the cooperation with the pain therapist or anaesthesiologist is required. I am convinced that, by early infusion treatments or drug therapy for the sedation of sympathetic hyperexcitability, improvements in results can be achieved. It stands to reason that psychological guidance for the patient must be taken into due account. PMID- 1283798 TI - Incubation chambers for the staining of ultrathin sections. An in situ technique especially suited for immunocytochemistry. AB - The preparation and use of incubation chambers for staining of ultrathin sections is described. As an example the immunogold staining is given which can be carried out in these devices in a more simple manner than normally possible, and with good results as shown by electron microscopy. PMID- 1283799 TI - Cytokeratin and vimentin heterogeneity in human cornea. AB - The body of information on cytokeratin expression in non-epithelial and epithelioid cells is steadily increasing. In this immunocytochemical study using a panel of monoclonal cytokeratin antibodies, we regularly observed cytokeratins no. 8 and 18 together with vimentin in the corneal endothelium of the human eye, but the antibodies exhibited a heterogeneous reactivity pattern. In fetal eye specimens, cytokeratins were already present at the 10th week of gestation, and disappeared at about the 22th week of fetal development. Corneal and conjunctival epithelial cells in the same specimens usually showed uniform cytokeratin 8 and 18 expression, beside the well documented presence of corneal and squamous epithelium type cytokeratins. In 2 of our 7 cases of adults, cells coexpressing cytokeratin and vimentin were observed in the corneal epithelium. The data provide another example of modulation of cytokeratin and vimentin expression, in which simplistic rules cannot be applied. PMID- 1283800 TI - Localization of NADPH diaphorase, a histochemical marker for nitric oxide synthase, in the mouse spinal cord. AB - NADPH diaphorase-reactive neurons and fibres are present within the entire spinal cord. Moderately to strongly stained neurons were found in the dorsal horn, in particular in lamina III, as well as around the central canal. A dense accumulation of stained neurons was localized in putative preganglionic sympathetic and parasympathetic nuclei. The somatic motor neurons of the ventral horn were found unlabelled. In view of the recently established identity of NADPH diaphorase with nitric oxide synthase, these results suggest that nitric oxide is involved in sensory and autonomic information processing in the spinal cord. PMID- 1283801 TI - Characterization of two porcine proinsulin reactive monoclonal antibodies by immunostaining of beta-cells in pancreatic sections of different species. AB - Murine monoclonal antibodies against porcine proinsulin were generated by somatic cell hybridization. As detected by radioimmunoassay, 2 monoclonal antibodies KSPI14D4 and KSPI13G10 showed a strong binding to 125I-labelled porcine proinsulin but not to insulin. The species specificity of these 2 monoclonals was found to be different as shown by indirect immunofluorescence using sections of Bouin-fixed pancreata of different species. The KSPI14D4 recognized the proinsulin of pig, mouse, man, cattle, rat, dog, and cat but not that of guinea pig, whereas the KSPI13G10 bound to porcine proinsulin only. From these results it is concluded that KSPI14D4 effectively recognizes a wide-spread epitope located in one of the insulin-C-peptide junctions of the proinsulin molecule, whereas KSPI13G10 is directed to a species-specific epitope of the porcine connecting peptide. PMID- 1283802 TI - Brain filament proteins in primary cultures derived from chick embryos early in development. AB - Brain filament expression and neurofilament post-translational modifications (phosphorylations) were studied in primary cultures derived from whole 3-4 day chick embryos. After 2-3 days in culture, neurofilament-positive cells formed neuronal aggregates connected by bundles of neurites in a distinctive pattern similar to that observed in cultures derived from embryonal rat brain and neonatal rat cerebellum. Aggregates and neuritic bundles were stained with several monoclonal antibodies reacting with phosphorylated neurofilament epitopes. With two monoclonal antibodies reacting with phosphorylated forms of the high molecular weight neurofilament subunit, staining was only observed after 8 and 10 days in vitro. There was a major difference between rat and chicken with respect to astrocyte differentiation in culture. In chicken, the flat cells surrounding the neuronal aggregates remained constantly GFAP-negative throughout the whole experimental period (10 days). GFAP-positive cells were first observed within the neuronal aggregates on day 8 in vitro. PMID- 1283803 TI - Perinatal morphine exposure alters peptidergic development in the striatum. AB - It has been reported that perinatal exposure to opiates affects mRNA synthesis, body growth and brain development in mammals, including humans. We have observed that morphine administration in drinking water during the perinatal period alters peptide development in the striatum of the rat. There is a marked increase in substance P and met-enkephalin content, the latter is maintained even at 30 days postnatally. The transient increase or earlier maturation of substance P content is correlated by a more precocious axon terminal organization as revealed by immunocytochemical staining. The increased metenkephalin content is correlated by a higher abundance of preproenkephalin A mRNA and this correlation is particularly evident at 15 days postnatally. At earlier times both northern blotting and in situ hybridization techniques fail to show any significant difference between control and morphine exposed rats, likely because the peptide content is not very different in the two groups or at least the gap is not as wide as at later times. PMID- 1283804 TI - Influence of cryopreservation on viability and nutritional microcirculation of islets of Langerhans. AB - Isolated pancreatic islets of Syrian golden hamsters were cryopreserved for 1 and 10 weeks, respectively. Following thawing islet mass was found more than 90%. Analysis of viability of these islets by dithizone staining revealed 94 +/- 4% (1 week cryopreservation) and 96 +/- 3% (10 weeks cryopreservation) positively stained islets. After implantation into dorsal skin-fold chambers of syngeneic animals, intravital fluorescence microscopy (5% FITC-dextran, i.v.) showed a regular microvascular network 10 days after implantation. The total diameter of the microvascular network was found similar in cryopreserved islets (day 10: 420.8 +/- 55.2 microns (1 week preservation) and 406.5 +/- 25.2 (10 weeks preservation)) as compared to non-preserved controls (day 10: 411.7 +/- 53.9 microns). Therefore we conclude that cryopreservation of hamster islet isografts for 1 and 10 weeks, respectively, does not alter viability as well as the potential for revascularization. Cryopreservation seems to be an adequate technique for long time storage prior to free transplantation. PMID- 1283805 TI - Serum protein concentrations in Plasmodium falciparum malaria. AB - In patients with uncomplicated Plasmodium falciparum infection cytokine-mediated serum protein levels of C-reactive protein (CRP), coeruloplasmin (COE), beta 2 microglobulin (B2M), alpha 1-acid glycoprotein (AAG), alpha 1-antitrypsin (AAT), haptoglobin (HPT), prealbumin (PRE), retinol binding protein (RBP), albumin (ALB) and transferrin (TRF) were measured in an endemic area of the Amazonian rain forest. Semi-immune (SI) and nonimmune (NI) patients were investigated. In both patient groups the serum concentrations of CRP, COE and B2M were elevated on admission. In addition AAG and AAT concentrations were increased in NI patients compared to control subjects. Significantly lower serum concentrations of HPT, PRE, RBP, ALB and TRF were seen in both patient groups during the acute phase of the disease, and were more pronounced in NI patients. After a 28-day follow-up, AAT and B2M were normal in SI patients but HPT, AAT and B2M were still significantly altered in NI patients. PMID- 1283806 TI - [Observation of the posterior urethra by transrectal linear ultrasonography]. AB - Transrectal linear ultrasonography was performed on 59 male patients with dysuria, and voiding movement of the posterior urethra was observed with a videomonitor. Uroflowmetry was performed simultaneously, and the results were compared with those obtained in a previous study. On the image synchronized with maximum flow rate, the diameter of the bladder neck, and the center of the prostatic urethra were measured as parameters and the correlation with maximum flow rate, average flow rate, and residual urine rate, was examined. The forward movement of the ventral side of the posterior urethra was found to play a more important role in the opening of the posterior urethra, than the opening of the bladder neck, and the width of the prostatic urethra to play a more important role in the efficiency of urination than the width of the bladder neck. PMID- 1283807 TI - [A case of staphylococcal enterocolitis caused by methicillin resistant Staphylococcus aureus]. AB - Recently, the frequency of methicillin resistant Staphylococcus aureus (MRSA) infection has been increasing. We experienced a case of postoperative enterocolitis due to MRSA. The patient was an 81-year-old male with benign prostatic hypertrophy. Urine leakage from the penrose drain tube appeared 1 day after suprapubic prostatectomy. We had used intravenous infusion of antibiotic agents including cefodizine (CDZM), imipenem (IPM/CS) and cefmetazol (CMZ). He developed severe diarrhea, high fever, oliguria, leg edema and ascites 24 days after the operation. MRSA was detected from his feces. Toxic shock syndrome toxin I (TSST-I) was produced by this bacteria the coagulase type of which was type II. The patient was treated with oral vancomycin (1 g/day), to which this bacteria showed sensitivity and the patient showed, improvement, including symptoms, leucocytosis and serum CRP level 12 days after administration of vancomycin. PMID- 1283808 TI - Acute phase proteins in "small for dates" babies. II. Haptoglobin, transferrin, alpha-1-feto protein, alpha-1-acid glycoprotein and caeruloplasmin levels. AB - Haptoglobin, transferrin, alpha-1-feto-protein (AFP), alpha-1-acid glycoprotein (AAGP) and caeruloplasmin levels were estimated in 14 "small for dates" (SFD) and 31 "appropriate for dates" (AFD) babies by the single radial immunodiffusion method. The mean caeruloplasmin levels was observed to be significantly reduced in the SFD babies when compared with the AFD babies (t = 3.4582, P < 0.02). None of the other 4 acute phase proteins showed any significant differences in mean concentration between the SFD babies and the controls. The diminished caeruloplasmin levels observed in SFD babies agrees with previous reports in post natal undernutrition. Our findings of no significant differences in the other 4 acute phase proteins between SFD and AFD babies are however at variance with previous observations of elevated levels of AFP, haptoglobin and AAGP and reduced levels of transferrin in malnourished infants. PMID- 1283809 TI - Clinical, hematological, and molecular features in Sicilians with Hb S-beta thalassemia. AB - The clinical, hematological, and molecular features of 81 patients with Hb S-beta thalassemia and relatives from 76 unrelated families are reported. We analyzed the beta-thalassemia mutations and the beta S haplotypes in all patients and detected 6 different beta-thalassemia alleles: codon 39 (C-->T) (39 cases), IVS-I 1 (G-->A) (12 cases), IVS-II-1 (G-->A) (4 cases), IVS-I-6 (T-->C) (6 cases), IVS I-110 (G-->A) (14 cases), and IVS-II-745 (G-->C) (6 cases). Eighty patients had haplotype #19 or the Benin type and one had haplotype #17 or the Cameroon type. The type of beta-thalassemia allele had the greatest influence on the phenotypic expression; this was observed for patients with Hb S-beta-thalassemia and for simple beta-thalassemia heterozygotes. The mild IVS-I-6 (T-->C) mutation produced borderline abnormal erythrocytic indices and Hb A2 levels in heterozygotes. Overall, there was a milder expression in beta(S) beta(+) patients (only 7.7% presented severe disease) than in those with the beta(S)beta(0) condition (22.6% had the severe form of the disease). PMID- 1283810 TI - Clinical course and molecular characterization of a compound heterozygote for sickle hemoglobin and hemoglobin Kenya. AB - We describe a 25-year-old black woman who presented with a long history of anemia requiring transfusions during childhood and adolescence. Molecular analysis revealed her to be a compound heterozygote for the sickle mutation and the approximately 22.7 kb deletion associated with hemoglobin Kenya. This patient's clinical course was more severe than previously reported for the Hb S/Hb Kenya genotype, a probable consequence of concomitant iron deficiency. PMID- 1283811 TI - Treatment of phenothiazine-induced agranulocytosis with recombinant granulocyte colony-stimulating factor. PMID- 1283812 TI - Foregoing life-sustaining treatment for adult, developmentally disabled, public wards: a proposed statute. AB - This Article proposes a procedure for making decisions to forego life-sustaining treatment for adult, developmentally disabled, public wards who are not competent to make health care decisions. Few commentators or cases address the special considerations involved in making life-sustaining treatment decisions for this patient population. The proposal attempts to fill this gap with a patient centered process that allows decisionmakers, without prior judicial approval, to forego life-sustaining treatment for adult, developmentally disabled, public wards who have been reliably diagnosed with specific medical conditions. PMID- 1283813 TI - Chimeric rat Na,K-ATPase alpha 1/alpha 3* isoforms. Analysis of the structural basis for differences in Na+ requirements in the alpha 1 and alpha 3* isoforms. AB - Na,K-ATPase molecules containing the alpha 1, alpha 2*, and alpha 3* isoforms expressed in HeLa cells exhibit a two- to threefold difference in their K0.5 for Na+ (alpha 1 = alpha 2* < alpha 3*). To investigate the structural basis for this difference, chimeric alpha 1/alpha 3* isoform cDNAs were constructed and expressed in HeLa cells. Na,K-ATPase containing each alpha isoform chimera was analyzed for its Na+ dependence properties. Results of these experiments do not reveal a region in the alpha 1 or alpha 3* isoform that is clearly responsible for the apparent affinity for Na+. It is possible that molecular interactions involving amino acids that span virtually the entire Na,K-ATPase molecule contribute to the determination of this parameter. PMID- 1283814 TI - Constraints on models for the folding of the Na,K-ATPase. AB - We have attempted to bring together in graphic fashion the available evidence on the structure of the Na,K-ATPase and the H,K-ATPase. There appears to be much room for modification of the existing models for transmembrane folding. More sites on each side of the membrane need to be identified. Whether these will be antibody epitopes, sites of covalent modification, or tags inserted by mutagenesis is less important than that there be many of them and that each be verified by alternative approaches. If any single principle has emerged from the study of the topography of membrane proteins, it is that it is easy to reach conclusions too soon. PMID- 1283815 TI - Epitope mapping by deletion mutants reveals the transmembrane topology of the plasma membrane Ca2+ pump. PMID- 1283816 TI - Monoclonal antibodies and the identification of functional regions of the Na+,K(+)-ATPase. PMID- 1283817 TI - Gene regulation by Ca2+ ATPases. Evidence from the use of thapsigargin, a specific inhibitor of intracellular membrane Ca2+ ATPases. PMID- 1283818 TI - The Alzheimer's amyloid precursor is cleaved intracellularly in the trans-Golgi network or in a post-Golgi compartment. PMID- 1283819 TI - Interactions of monocrotophos and quinalphos with Anabaena torulosa isolated from rice soil. AB - The interaction of insecticide combinations of monocrotophos and quinalphos on Anabaena torulosa, by the criteria of absorbance (OD) and packed cell volume (PCV) of the culture, content of chlorophyll a, phycocyanin, carotenoids, total protein, DNA and RNA, heterocyst differentiation and nitrogen fixation, were assessed. In general, monocrotophos and quinalphos, in combination, interacted significantly yielding three different responses viz., additive, antagonistic or synergistic. The nature of the interaction found with OD and PCV was nearly the same for a particular concentration of the insecticides. However, no consistent interaction was observed with respect to carotenoids and phycocyanin. The three types of interaction were noticed for total protein, DNA and RNA. Interestingly, the insecticide combinations at lower concentrations yielded all interaction responses for heterocyst frequency and nitrogenase activity. But, higher concentrations, in combination, resulted in synergism for heterocyst differentiation and nitrogen fixation. PMID- 1283820 TI - Specific incorporation of kinetin into eukaryotic and prokaryotic transfer ribonucleic acid molecules. AB - We show that kinetin, a non-natural product with strong cytokinin activity, is incorporated into prokaryotic and eukaryotic tRNAs in the exchange reaction catalysed by a putative tRNA-kinetin transglycosylase. We also show that kinetin is specifically incorporated into E. coli tRNA(Tyr) and most probably at position 37. To our knowledge, this is the first report of a nucleic acid base exchange reaction occurring at this position. PMID- 1283822 TI - Malaria in the Americas. PMID- 1283821 TI - Physiological activities of S-(1,2-dicarboxyethyl)glutathione as an intrinsic tripeptide present in liver, heart and lens. AB - S-(1,2-Dicarboxyethyl)glutathione (DCE-GS, CAS 1115-52-2) found in rat liver, heart and lens in considerable amounts, showed an anti-inflammatory effect, which was evaluated by testing the inhibition of the experimental conjunctival edema of rats. An intravenous injection (3 mg/kg) prior to the carrageenan injection prevented the conjunctive edema formation by up to 30%. This peptide also inhibited the histamine release from rat mast cells induced by the compound 48/80. The peptide was added to the mast cells before addition of the compound 48/80 and an inhibition of the histamine release up to 96% at a 1 mmol/l concentration occurred. Furthermore, it displayed an antianaphylactic effect in rats using antibody against chicken egg albumin. An injection of the peptide (30 mg/kg) prior to the antigen administration inhibited color deposition up to 43%. Analogues or derivatives of DCE-GS were synthesized and tested for those inhibitory activities. However, there was no other peptide having stronger effects than DCE-GS and little structure-activity relationship among them. PMID- 1283823 TI - Tobacco or health: status in the Americas. PMID- 1283824 TI - The social model of health practices. PMID- 1283825 TI - [Complex studies of virology, microbiology, biochemistry and epidemiology in the adults of a semi-closed community vaccinated against influenza with the inactivated NIVGRIP vaccine intranasally]. AB - A study was conducted on the specific and non specific immunomodulator effects of the inactivated vaccine NIVGRIP. The results revealed the seroconversion of HAI antibodies against influenza and mumps viruses and the reduction of viral and microbial flora of the pharynx. The kinetics of some proteins specific to the acute stage (siderophiline antitrypsin, microglobulin, complement C1q and C2 factors, C reactive protein and fibronectin) was also investigated and significant quantitative modifications were noticed in vaccinated subjects. The mean illness duration (acute respiratory disease) was three times as short in vaccinated subjects as in controls. PMID- 1283826 TI - Coexpression of vimentin, cytokeratin and S-100 in monomorphic adenoma of salivary gland; value of marker studies in the differential diagnosis of salivary gland tumours. AB - An unusual coexpression of glial fibrillary acid protein (GFAP), keratin and vimentin occurs in pleomorphic adenoma of salivary gland. We designed this study to see if coexpression of the markers was also present in monomorphic adenoma of the salivary gland and whether monomorphic adenoma could be distinguished from other salivary gland tumours by marker studies. Immunocytochemical markers were used on fine needle aspiration samples from four cases of monomorphic adenoma, two cases of oncocytic adenoma, three cases of adenoid cystic carcinoma and four cases of pleomorphic adenoma. While positivity for cytokeratin, vimentin and S 100 was consistently found in all cases of monomorphic adenoma, only cytokeratin was expressed in adenoid cystic carcinoma. In pleomorphic adenoma, GFAP, cytokeratin and vimentin were coexpressed while in cases of oncocytic adenoma none of the markers was localized. Thus, it appears that by using a combination of GFAP, cytokeratin, vimentin and S-100 a distinction between these neoplasms may be possible. However, a larger study is needed to establish the usefulness of this approach. PMID- 1283827 TI - Inhibitory effect of substituted dextrans on MCF7 human breast cancer cell growth in vitro. AB - Substituted dextrans can reproduce some of the properties of heparin and can thus be used to alter cellular growth. We studied the effect of heparin (H108), dextran (D), carboxymethylbenzylamide dextran (CMDB) and carboxymethylbenzylamide sulfonate dextran (CMDBS) on the growth of human mammary cells of the MCF7 tumor line. The cells were cultured in minimum Eagle's medium containing 2% fetal calf serum without biopolymer, or with increasing concentrations of H108, D, CMDB or CMDBS. Growth curves were accurately based on cell counting using a Coulter counter. Cell distribution in the various phases of the cycle was analyzed by flow cytometry. Dose-dependent growth inhibitory effects (400-4000 micrograms/ml) were observed. The effect on MCF7 tumor cells was most apparent with CMDBS. The percentage of cells in the S phase decreased with preferential blocking in the G0/G1 phase. Pre-clinical studies can be anticipated as there is an absence of in vivo toxicity. PMID- 1283828 TI - Bleomycin but not its derivatives inhibits the in vivo shedding of a rat tumor associated antigen. AB - Rat fibrosarcoma (KMT-17) cells and their in vitro clone, 10% FCS A3 cells, shed a tumor-associated antigen (TAA), CE7, from the cell surface under growth promoting conditions. We treated cells with the antitumor agent bleomycin (BLM) and its analogs peplomycin and liblomycin in vitro and in vivo in an attempt to increase expression of this antigen and induce an antitumor response. Although all three agents enhance antigen expression in vitro, proportionate to their direct antiproliferative effects, only BLM enhances antigen expression in vivo. The in vivo regulation of CE7 expression appears not to be related to the direct cytotoxic effects of the antitumor agents but rather to the immuno-augmenting effects of BLM. PMID- 1283829 TI - Immunohistochemical investigation on the presence of chondroitin sulfate in calcification nodules of epiphyseal cartilage. AB - Chondroitin sulfate localization in mouse epiphyseal cartilage was studied using CS-56 monoclonal antibody immunospecific for the glycosaminoglycan portion of the molecule. For light and fluorescence microscopy, decalcified specimens were embedded in paraffin, Lowicryl, or were frozen and cryostat-sectioned, and the antigen-antibody reaction was demonstrated by treating sections with IgM peroxidase, IgM-alkaline phosphatase, or IgM-fluorescein conjugates. For electron microscopy, decalcified and undecalcified specimens were embedded in Lowicryl; ultrathin sections from undecalcified specimens were decalcified by flotation on EDTA; sections from both types of specimens were treated with IgM-immunogold conjugate for demonstration of CS-56 reaction. Before immunoreaction, part of all decalcified sections were digested with Streptomyces or testicular hyaluronidase. Control sections were treated with either mouse and goat non-immune serum, or mouse monoclonal antiserum to human dendritic reticulum cells. Both light and electron microscopy show CS-56 reaction with cytoplasmic components of maturing and hypertrophic chondrocytes. Under the light microscope, immunoreaction was not visible in calcified matrix, and was visible in uncalcified matrix only after hyaluronidase digestion. Under the electron microscope, it was evident both in uncalcified and calcified matrix, although the latter showed few immunogold particles, usually placed on areas which appeared incompletely calcified. Gold particles were chiefly distributed at the periphery of calcification nodules and fully calcified matrix. These results show that CS-56, besides reacting with cytoplasm of maturing and hypertrophic chondrocytes, binds to crystal ghosts and other components of cartilage matrix, immunoreactivity decreasing as calcification increases. This suggests that chondroitin sulfate molecules are either degraded during calcification, or segregated into macromolecular complexes, or both degraded and segregated. The second possibility is supported by the increase of immunosensitivity induced by hyaluronidase digestion. PMID- 1283830 TI - Immunohistochemical and electron microscope studies of rat islets of Langerhans one month after adult thymectomy. AB - Ultrastructural and quantitative immunocytochemical studies of rat pancreata were carried out 1 month after adult thymectomy. The proportions of insulin-, glucagon , and somatostatin-immunoreactive cells in the pancreas were estimated on paraffin sections using the unlabelled peroxidase-antiperoxidase method. Relative islet volume, islet size and number were determined on hematoxylin and eosin stained sections. A moderate increase of the islet volume on account of size was found in the pancreas of the thymectomized rats. The proportion of insulin immunoreactive cells was also elevated. Ultrastructural studies showed a rich supply of secretory granules in most beta-cells. Mixed beta-endocrine-acinar cells were often observed. Mitotic figures were found in single beta-cells. The blood glucose level was in the normal range. The findings suggest a moderate stimulation of beta-cell secretory activity after thymectomy which is not associated with elevated blood glucose levels. PMID- 1283831 TI - Nerve growth factor receptor immunoreactivity in non-nervous structures of the adult rat brain. AB - The non-neuronal distribution of nerve growth factor receptors (NGFr) in the adult rat brain was investigated immunohistochemically using an anti-NGFr monoclonal antibody (192-IgG). In addition to the neurons known to be NGF dependent or containing NGF binding-sites, a moderate to strong NGFr immunoreactivity was observed in several non-nervous tissues such as the ependymal cells, the epithelial cells of the choroid plexus, the leptomeninge and the cerebral blood vessels. Vascular immunoreactivity for NGFr occurs in the adventitia and muscular layers of the large arteries (circle of Willis) and, apparently, in all the wall layers of the intermediate or small (pial-arachnoid) arteries. The present results provide direct evidence for the presence of non neuronal NGFr in the brain of adult rats, and suggest a possible involvement of NGF in roles other than those classically thought. PMID- 1283832 TI - GFAP-immunoreactive perivascular glia in the chick optic tectum. AB - Immunocytochemical staining of the glial fibrillary acidic protein (GFAP) was utilized to characterize the processes of the astrocytes enveloping the vessel wall in the central nervous system. The study was carried out in the mesencephalic lobes of 18 and 20 incubation-day chick embryos and of 20 day chickens. A perivascular GFAP positivity was mainly detectable in the vessel portions running within the tectum white layers, while it was scarce, or absent, in the grey ones. The perivascular GFAP negativity in the tectum cellular layers was not considered result of the absence of astrocytic endfeet since our previous electronmicroscopical studies evidenced an almost complete perivascular astrocytic ring throughout the tectum layers at hatching time. Present data rather suggest that the expression of the GFAP-made intermediate filaments in developing astrocytes might be controlled by the surrounding microenvironment. PMID- 1283833 TI - Brain natriuretic peptide (BNP)-like immunoreactivity in the central nervous system of the crested newt. AB - The distribution of brain natriuretic peptide (BNP)-like immunoreactivity (ir) was studied in the brain of a urodele amphibian, the crested newt Triturus carnifex Laur. BNP-like immunoreactive neurons were found mainly in the caudal hypothalamus (retro- and supra-chiasmatic areas) and in the preoptic area. A widespread innervation throughout the brainstem as far as the spinal cord was also observed. By double immunostaining (after section incubation with a-BNP and a-tyrosine hydroxylase-TH-antibodies), close topographical relationships between BNP-like and TH-like immunoreactive neurons within the hypothalamus were found. PMID- 1283834 TI - Comparative study of glial fibrillary acidic protein (GFAP)-like immunoreactivity in the retina of some representative vertebrates. AB - A polyclonal glial fibrillary acidic protein (GFAP) antiserum was used to study the distribution of GFAP-like immunoreactivity in the retina of adult vertebrates (teleosts, amphibians, reptiles, birds and mammals). GFAP-positive Muller cells were demonstrated in all the species studied, although with different degrees and patterns of immunoreactivity. In nonmammalian vertebrates, Muller cells were the only immunoreactive retinal elements. The staining was located throughout the retina of the species examined, with the exception of the rabbit, which exhibited regional variability in the expression of GFAP. The data indicate that GFAP expression in retinal Muller cells is a common feature of a wide variety of adult vertebrate species. PMID- 1283835 TI - On the expression of cytokeratins and their distribution in some rabbit gland tissues. AB - The composition and distribution of cytokeratins were studied in a series of exocrine and endocrine glands in the rabbit, by means of anti-human monoclonal antibodies. Rabbit cytokeratins are known to be homologous to those in man, and their in situ distribution was also found to be similar. In acinic cells of the exocrine glands, only cytokeratins 8 and 18 were detected, whereas in ductal cells 1, 5, 10, 11 and 13, 19 were also present. The myoepithelial cells surrounding acini and basal duct cells were stained with the antibodies directed against cytokeratins 13 and 1, 5, 10, 11. Among the endocrine glands, a higher reactivity was observed in the thyroid gland and pancreatic islets, while pituitary and adrenal gland often remained unstained. Although the expression of cytokeratins was found to be almost homogeneous in each glandular cell type, a certain variability was observed, depending on the organ examined and the treatment carried out. PMID- 1283836 TI - An immunohistochemical study of the distribution of ABH antigens in human submandibular glands at the light and electron microscopic levels. AB - The distribution of blood group antigens ABH in submandibular glands was studied at light and electron microscopy levels by applying ImmunoGold Silver Staining (IGSS) and post-embedding ImmunoGold (IGS) methods, respectively. In IGSS treated samples, a cytoplasmic and a surface form of antigen localization were discernible in the glandular parenchyma. The former was restricted to most mucous cells and to scattered serous cells: A and B antigens were demonstrated in mucous cells of A and B type glands, while H antigen appeared in most mucous and occasional serous elements regardless of the blood type of donors. The latter appeared as a strong H reactivity on cell surfaces of serous acini and ducts regardless of the patient blood type. The IGS method was applied both on non osmicated samples embedded in LR White resin and on osmicated, Epon embedded samples. In non-osmicated tissues, antigen labelling was revealed in secretory granules and cell surfaces. Positive secretory granules were found in most mucous cells and occasional serous, intercalated, and striated duct cells. A and B antigens weakly reacted in mucous cells of A and B type glands, respectively, while strong H reactivity was seen in mucous, serous, intercalated and striated duct cells of glands of all types. Surfaces labelled with H antigen were found on both lumenal and basolateral membranes of striated ducts in glands of all types. IGS method applied on osmicated, Epon embedded samples, selectively revealed blood group antigens in secretory granules of serous cells but not in the apical vesicles of striated ductal cells. Cell surfaces were completely unreactive. PMID- 1283837 TI - Role of mast cells in health: daily rhythmic variations in their number, exocytotic activity, histamine and serotonin content in the rat thyroid gland. AB - A chronobiologic transverse study on rat thyroid has been carried out to investigate whether mast cells and their content in biogenic amines normally undergo daily variations and whether these are related to circadian activity of the gland. The mean number of mast cells per microscopic field presents daily variations ranging from 10.9 +/- 3 to 14.6 +/- 3.8 in males and from 8.4 +/- 1.9 to 14.8 +/- 3 in females: these variations show a circadian trend in both sexes, with a 12 hrs period and two peaks at about 11:10/23:10. The mean percentage of degranulated mast cells per microscopic fields shows daily variations ranging from 51 +/- 11 to 60.4 +/- 14.2 in males and from 49.8 +/- 12.5 to 58.3 +/- 13.6 in females; these variations present a circadian rhythm with a 24 hrs period and a mean peak at 02:00. The histamine content of the gland varies in 24 hrs from 20.93 +/- 1.19 micrograms/g w w to 38.08 +/- 1.7 micrograms/g w w, without any sex-related difference: these variations show a rhythmic trend with a 12 hrs period and two peaks at 09:10/21:10. Serotonin content of thyroid presents circadian variations from 15.98 +/- 0.83 to 23.23 +/- 0.61 micrograms/g w w, with a 12 hrs period and two peaks at 04:20/16:20. Whereas the variations of mast cell exocytosis and of serotonin content seem to be chronobiologically linked to circadian variations of gland activity, evaluated on the basis of free and total tetraiodothyronine serum levels, the variations of mast cell number appear to be related to those of thyroid and blood histamine. The present data support the hypothesis that mast cell activity should not be considered as only linked to inflammation or allergic responses. PMID- 1283838 TI - Enzyme immunoassay for prostate-specific antigen and its diagnostic application in prostate cancer. AB - The purpose of this study was to develop a reliable screening test for prostate cancer. Monoclonal antibodies specific to the prostate-specific antigen (PSA) were generated with an improved hybridoma technique. The hybrid cells were initially cultured in a semisolid medium containing methylcellulose and later transferred to a liquid medium for further subculture. Thirty-six out of a total 1,250 recovered colonies were shown to exhibit a high affinity to PSA by radioimmunobinding assay. Eight hybrid cell lines which secreted either IgG1 or IgG2a antibodies of a high affinity and specificity were established for evaluation. The association constants between PSA and these monoclonal antibodies were shown to range from 1 x 10(9) to 5 x 10(9) M-1. From the results of a matrix cross-matching procedure, pairs of monoclonal antibodies were identified and the corresponding epitopes assigned, and most of them could also be paired with rabbit anti-PSA in a typical sandwich enzyme immunoassay. The designated EIA procedure was performed over 90 minutes at room temperature in a two-stage incubation protocol with a sensitivity of 0.4 ng/mL. The EIA kit was shown to have little cross-reactivity with thyroid stimulating hormone, alpha-fetoprotein, carcinoembryonic antigen and prostate acid phosphatase. Preliminary evaluations with clinically defined patients' sera revealed that proper selections of antibody pairs in sandwich immunoassays are crucial to the adequate performance of the EIA kits. PMID- 1283839 TI - Modulation of extracellular matrix glycoproteins production by in vitro interacting conditions between rat colonic fibroblasts and tumoral cells. AB - Mixed cultures of fibroblasts with rat colon carcinoma cell lines were used to investigate the production of extracellular matrix glycoproteins. Tumoral cells were shown to influence their production in different ways depending on the cell clone (PROb cells which in vivo produce progressive tumors and REGb cells which produce regressive ones) but also on the relative proportions of stromal and tumoral cells. When fibroblasts were predominant, the REGb cells containing mixture produced higher levels of all protein studied as compared with the PROb cells containing system. When the situation was reversed in favor of tumoral cells, REGb cells containing cocultures still produced more fibronectin, laminin and undulin, but the difference with PROb ones was reduced. On the opposite, cocultures enriched with PROb cells made more entactin and SPARC and approximately equal amounts of tenascin. PMID- 1283840 TI - In vitro angiogenesis in fibrin matrices containing fibronectin or hyaluronic acid. AB - Angiogenesis involved numerous interactions between extracellular matrix and endothelial cells which may exhibit changes in actin filament distribution. Using an in vitro model, capillary endothelial cells were grown in fibrin matrix containing fibronectin or hyaluronic acid. Actin filament distribution, nucleus localization and cell morphology were observed. Preliminary study showed the formation of tube-, branche- and capillary-like structures within fibrin. In the presence of both fibrin and fibronectin, cells with actin filament stress fibers were more spreading than those in fibrin. In the presence of hyaluronic acid, tubes were limited in extension into the fibrin. In addition, the study of co localization of nucleus and actin filaments showed different cell behaviours. Migratory cells seem to arrange in parallel to each other and a capillary-like structure may be formed at the proximal extremity of this cell pattern. PMID- 1283841 TI - Selective beta 1 and beta 2 adrenoceptor blockade on epinephrine-induced arrhythmias in halothane anaesthetized dogs. AB - Beta 2 as well as beta 1 adrenoceptors have been recognized in the heart of vertebrates. They mediate a positive chronotropic action of catecholamines. We compared the effect of selective beta 1 and beta 2 adrenoceptor antagonists on the genesis of halothane-epinephrine arrhythmias in dogs. The arrhythmogenic dose (AD) of epinephrine was increased in the presence of l-metoprolol, a selective beta 1 antagonist (8.40 +/- 1.13 micrograms.kg-1 x min-1; mean +/- SEM), compared with control value (2.62 +/- 0.56) (P < 0.05). In contrast, ICI-118,551, a selective beta 2 antagonist, did not change the AD (2.36 +/- 0.43). Adding ICI 118,551 to l-metoprolol did not affect the AD of epinephrine in the presence of l metoprolol alone (6.34 +/- 0.74 vs 8.40 +/- 1.13). These results suggest that selective beta 1 blockade is effective in preventing halothane-epinephrine arrhythmias, but selective beta 2 blockade is not. PMID- 1283842 TI - [The influence of acupuncture on interleukin 2 interferon-natural killer cell regulatory network of kidney-deficiency mice]. AB - The influence of acupuncture on IL2-IFN-NKC regulatory network was investigated, experiments were performed on kidney-deficiency mice received the treatments of acupuncture of "Zusanli" point. The results showed that the interleukin: (IL:), natural killer cell (NKC) activity and interferon (IFN) from the kidney deficiency mice were lower than that from the normal mice. Acupuncture increased the levels of all the IL2 and NKC activity, acupuncture promoted Newcastle disease virus (NDV) inducing the IFN of kidney-deficiency mice, but also induced the IFN directly. The results suggests that acupuncture could make positive adjustment to IL2-IFN-NKC regulatory network. It provided new theoretical basis for the principles of acupuncture theory on IL2-IFN-NKC regulatory network put forward in recent years. PMID- 1283843 TI - Recombinant human G-CSF and retinoic acid in synergistically inducing granulocyte differentiation of human promyelocytic leukemic cells. AB - The effects of recombinant human G-CSF (rhG-CSF) and retinoic acid (RA) were studied on the proliferation and differentiation of HL-60 cells and human acute myeloid leukemic cells. Synergistic effect on granulocyte differentiation was observed when HL-60 cells and primary acute promyelocytic leukemic cells were cocultured with RA plus rhG-CSF. rhG-CSF combined with RA increased more significantly the percentage of mature cells than RA alone and greatly increased NBT reduction activity (P < 0.001). These results suggested that proliferated effect of rhG-CSF on leukemic cells may be important for inducing differentiation of myeloid leukemic cells. But this effect might expose the patients to the risk of acute myeloblastic leukemia if G-CSF was used alone. However, RA could not only rule out the latter situation but retain former merit as well. The authors suggest that the combined use of G-CSF with RA is probably a new approach to the treatment of leukemia. PMID- 1283844 TI - Pseudomonas pseudomallei and melioidosis in China. AB - Though melioidosis has been reported since 1912, it is still a new problem for most Chinese physicians and medical scientists. Because of the lack of understanding and clinical experiences in melioidosis, none had been reported until 1990 in the mainland of China. In view of China's open policy and health work the natural foci of Pseudomonas pseudomallei in South China, ie. Hainan, Guangdong and Guangxi Provinces, should be given sufficient concern. Efforts should be made in training physicians in the endemic areas to improve their knowledge about the disease and to avoid misdiagnosis. PMID- 1283845 TI - [Distribution of bone morphogenetic protein in human bone and tooth germs: analysis of specificity of monoclonal antibody against bone morphogenetic protein]. AB - A cell strain stably secreting monoclonal antibody against BMP was obtained by hybridoma technique. The monoclonal antibody specifically reacted with the cells of human bone and tooth germs on paraffin embedded tissue sections. Immunohistochemical staining shows that BMP is distributed along collagen fibres in normal bone, also exist in osteoid tissue of new bone, in osteoblasts and in the cells of bone marrow. BMP may be found in human tooth germs such as in predentin, in the cells of outer and inner enamel epithelium, in the cells of dental sac generating alveolar bone. The results demonstrate that generation and growth of human bone and development of tooth germs have relation to BMP. The results at the molecular level prove that some antigenic determinants of human and bovine BMP are the same. BMP function activity inhibition test suggests that this antibody may block the function group of BMP. The ability of the monoclonal antibody to detect antigen and to inhibit generation of new bone makes it potentially useful in purification of BMP and in treating osteosarcoma and other bone tumors. PMID- 1283846 TI - Preclinical and clinical pharmacology of vinca alkaloids. AB - Vinca alkaloids, including vinblastine, vincristine, vindesine and vinorelbine, are widely used antineoplastic drugs, either as single agents or in combination with other drugs. The mechanism of action of these cell cycle-dependent agents is the inhibition of tubulin polymerisation into microtubules. Numerous studies have been conducted in animals and humans, using various in vivo and in vitro models, to investigate the pharmacological behaviour of this class of antitumour drug. Studies in cellular pharmacology demonstrate that vinca alkaloids are transported by multiple mechanisms, including passive diffusion and energy- and temperature dependent active transport systems. Moreover, active efflux of drug is involved in the P-glycoprotein-mediated multidrug resistance to vinca alkaloids. This phenomenon may be modulated, in vivo and in vitro, by calcium antagonists and calmodulin inhibitors. The clinical pharmacokinetics of vinca alkaloids after intravenous bolus injection, continuous infusion and oral administration are characterised by a large apparent total volume of distribution, high total plasma clearance and long terminal elimination half-life. Biliary excretion is the main elimination pathway, with low urinary excretion. Pharmacokinetic parameters of vinca alkaloids are time- and dose-dependent, and large inter- and intra individual variabilities have been observed. Human hepatic P-450IIIA cytochromes are involved in the metabolism of vindesine, vinblastine and probably other vinca alkaloids. Therefore, the possibility of drug-drug interactions must be considered when coadministering drugs in combination cancer chemotherapy. Development of newer semisynthetic analogues of vinca alkaloids and conjugation of vinca alkaloids with monoclonal antibodies may result in derivatives with increased antitumour activity and less clinical toxicity. PMID- 1283847 TI - Systemic therapy of advanced breast cancer. AB - Many cytotoxic agents have demonstrated activity in advanced breast cancer, the more active agents being cyclophosphamide and the anthracyclines doxorubicin and epirubicin. Combinations of drugs are generally superior to single agents in terms of response rate, duration of response and survival. The treatment of advanced breast cancer can be continued either until treatment failure, or for a limited time from either initiation of therapy or from the observation of complete response. Although these are issues of significant concern, data from randomised trials are limited, and so the question of optimal treatment duration remains open. Randomised trials comparing regimens that differ by a dose intensity factor of less than 2 have failed to demonstrate significant differences in efficacy between the dose levels. With higher doses, as applied in combination with colony-stimulating factors and bone marrow transplantation, response rates seem to increase, but whether this translates into improved survival has not yet been answered by the results of randomised trials. Approximately 30% of patients respond to endocrine therapy. From the results of randomised trials, which have compared the efficacies and toxicities of different endocrine modalities including combined endocrine therapy, single-agent tamoxifen is generally considered as the preferred first-line treatment, leaving progestins and aromatase inhibitors as alternatives for second-line endocrine therapy in responders. In the majority of trials, chemotherapy combined with endocrine therapy has given improved response rates compared with chemotherapy alone, but the differences have not generally been translated into prolonged survival with combined modalities. This gives rise to the question of the optimal sequence of chemotherapy and endocrine therapy, a subject needing further evaluation in future trials. PMID- 1283848 TI - A review of the antitumour activity of vinorelbine in breast cancer. AB - The use of vinorelbine 30 mg/m2/week as a single-agent treatment in advanced breast cancer has achieved response rates of > 20% as second-line treatment and 40 to 50% as first-line treatment. The major toxicity of the drug is reversible neutropenia; 35 to 50% of treated patients have grade IV neutropenia. The agent did not induce thrombocytopenia and proved mildly emetogenic and neurotoxic. Activity was confirmed in combination with fluorouracil or doxorubicin, when response rates ranging from 60 to 74% were achieved. Thus, vinorelbine appears to be a promising agent in the treatment of advanced breast cancer. PMID- 1283849 TI - The current and future place of vinorelbine in cancer therapy. AB - Vinorelbine is a new semisynthetic vinca alkaloid that differs chemically from vinblastine by a substitution of the catharanthine moiety. The antitumour activity of vinorelbine against murine tumours, human malignant cell lines and human tumour xenografts in nude mice is evidence of its powerful cytostatic activity against all tumour types. Phase I and phase II studies of intravenous vinorelbine, administered weekly as a single agent or in combination chemotherapy, have been conducted since 1985. Results suggest that vinorelbine has high activity in non-small cell lung cancer (with an overall response rate of 33 to 65%), breast cancer (overall response rate of 46 to 78%) and cisplatin resistant ovarian carcinoma (over-all response rate of 16% and 35% with single agent and combination therapy, respectively). In Hodgkin's disease, vinorelbine as a single agent demonstrates high activity, with overall responses ranging from 34 to 90%. Recent phase II studies assessing vinorelbine administered by continuous infusion or orally show promising response rates; however, further trials are needed to validate these preliminary results. PMID- 1283851 TI - Vinorelbine. A review of its antitumour activity in lung cancer. AB - Vinorelbine is a new semisynthetic vinca alkaloid. Data from in vitro and in vivo preclinical studies suggest that vinorelbine is active in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). There are at present no clinical data on the activity of vinorelbine in patients with SCLC. The response rate with single-agent vinorelbine in patients with NSCLC was 30% overall in two phase II studies including a total of 153 patients; all responses were partial. Response rates of 14 and 33%, respectively were observed in 2 randomised studies, with 1 response of 41 being complete. Vinorelbine is among the most active single drugs in the treatment of NSCLC, but comparative studies with other vinca alkaloids are lacking. Combinations of vinorelbine with cisplatin have shown response rates of 28 to 33% in 2 studies. The drug is well-tolerated in patients with NSCLC. Leucopenia is a dose-limiting factor, while peripheral neurotoxicity does not appear to be a problem. PMID- 1283850 TI - Current options in the treatment of non-small cell lung cancer. AB - Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in industrialised countries, with an overall 5-year survival rate of less than 10%. Good patient performance status is associated with a significantly improved prognosis, whereas the presence of metastases, particularly to the bone or liver, is associated with a poor outcome. Disease staging has largely been standardised using the tumour, node, metastasis (TNM) system, and also provides significant prognostic information. More recently, several biomarkers have been identified in patients with NSCLC, although their prognostic relevance remains to be established. Surgery, when feasible, is the treatment of choice in patients with NSCLC. However, most patients present with locally advanced disease that is not completely resectable. The use of combination chemotherapy regimens has generally been restricted to patients with metastatic, recurrent or unresectable disease, and several relatively active drugs that are generally used in combination have been identified. Combination chemotherapy either alone, or with surgery and/or radiotherapy, has produced some improvements in response rates and, in the neoadjuvant setting, has allowed complete resection in an increased number of patients with otherwise marginally resectable disease. There is also evidence that this approach may increase both disease-free interval and survival time. Thus, the most active chemotherapy regimens (generally those including cisplatin and a vinca alkaloid) appear to provide some benefit in patients with advanced non-small cell lung cancer, but the identification of more active combinations remains a priority. PMID- 1283852 TI - Benign prostatic hyperplasia: antecedents and natural history. PMID- 1283853 TI - A gel of glycosaminoglycans lining the anterior and posterior chambers in man: histochemical evidence at light and electron microscopy levels. AB - A thin mucous layer covers the ciliary body and iris epithelium and becomes thicker in the anterior chamber where it covers the anterior surface of the iris, the chamber angle and corneal endothelial surface. It is especially thick at the chamber angle, where it adopts a meniscus shape with the concavity towards the anterior chamber. Cetylpiridinium chloride along with glutaraldehyde was used to precipitate this layer of mucous substance lining the anterior and posterior chambers of the human eye. The staining of the precipitate by cationic dyes suggests that glycosaminoglycans are main components. The specific characterisation with anti-hyaluronic acid monoclonal antibody labelled with colloidal gold reveals the presence of hyaluronic acid in the precipitate. Long unbranched hyaluronic acid molecules may form the skeleton of a gel able to trap and hold virtually any other macromolecule suspended in the aqueous humour. A possible role of such a gel in the regulation of aqueous humour outflow is discussed. PMID- 1283854 TI - Occlusion of the central retinal artery and ocular neovascularisation: an indirect association? AB - Ocular neovascularisation is recognised as an uncommon complication of central retinal artery occlusion (CRAO) but has been associated most frequently in those patients suffering from carotid artery occlusive disease. We report the finding of neovascularisation after CRAO in a group of 8 patients, who have presented over the previous 6 years. Four showed no evidence of atherosclerotic carotid disease and only 2 were diabetic. Although the group numbers are necessarily small, it is suggested that these cases support the assertion that ocular neovascularisation may occur following CRAO in the absence of any underlying and predisposing ischaemic or inflammatory condition. PMID- 1283855 TI - Acidic fibroblast growth factor accelerates the healing of acetic-acid-induced gastric ulcers in rats. AB - Acidic fibroblast growth factor (aFGF) was evaluated for the healing of acetic acid-induced gastric ulcers in rats. The effect of aFGF on angiogenesis in the gastric ulcer bed was determined by the carmine dye infusion method, while its effect on gastric acid secretion was assessed in chronic gastric fistula rats. Oral treatment with aFGF, in the presence of heparin, reduced (ED50 value = 30.2 micrograms/kg/day) the acetic-acid-induced gastric ulcer area, when assessed 1 week later. aFGF was about 1,333-fold more potent than famotidine for healing such ulcers. At a dose of 200 micrograms/kg/day, aFGF increased the carmine density 3-fold and correspondingly reduced (80%) the gastric ulcer area. Thus, the ulcer healing effect of this agent involves angiogenesis in the gastric ulcer bed. This effect of aFGF appears to be unrelated to an inhibition of gastric acid secretion, as it was ineffective in chronic gastric fistula rats. In summary, oral aFGF significantly accelerates the healing of experimental gastric ulcers in rats. It may be a potent and effective agent for the treatment of peptic ulcers in humans. PMID- 1283856 TI - Hodgkin's disease: summary of twenty years' experience. AB - BACKGROUND: A retrospective analysis on HODGKIN'S DISEASE (HD) was finalized to see if changing the management and therapy during the years we improved the cure rate of lymphomas and reduced the incidence of side effects due to therapy. Up to twenty years' experience was based in two major therapeutic periods: the first included patients observed between 1970 and June 1980 and the second between July 1980 and December 1987. Significant differences between the two periods were the reduction of splenectomies as staging procedure, the reduction of radiation dose and extension and the sequential use of MOPP/ABVD instead of MOPP alone. METHODS: The analysis included all patients observed over the twenty years under study by looking to the differences concerning response to therapy, survival, relapse-free survival and major consequences due to therapy, namely death not directly related to lymphoma. 377 pts entered the first period and 193 the second one with a minimum follow-up of 4 years. RESULTS: Significant differences were recorded on CR rate, 80.9% vs 90.5%, respectively (p = 0.0024) and deaths in CR, 15.1% vs 2.6%, respectively (p = 0.000). The overall survival shows a probability of 60% and 83% at 11 years for the first and the second group, respectively (p = 0.000) being the probability of survival of 50% at 20 years for the first group of pts. The probability of being in remission is similarly of 79% and 78%, for the first and second group, respectively. The risk of death in remission accounting all causes not related to lymphoma shows a 17% probability vs 6% at 11 years (p = 0.006) for the first and second group, respectively, being 38% for the former group at 20 years. The most frequent single cause of death in remission was secondary leukemia which was recorded in 14 pts on the group of pts observed between 1970 and 1980, all splenectomized and treated by MOPP and extensive radiotherapy. CONCLUSIONS: The modifications of therapy of HD have produced improvements concerning the prognosis of pts; these improvements are due mainly to the reduction of late side effects such as acute leukemia and second solid tumor, and to the increase of remission rate and cure rate of the lymphoma. PMID- 1283857 TI - A simple radioassay for detection of antithyroglobulin autoantibodies. AB - Radioassay technique for detection of anti-thyroglobulin autoantibodies (ATA) in serum samples using protein-A rich Staphylococcus aureus as an immune complex separating agent was comparable (r = 0.99; n = 42; P < 0.001) to that evaluated with anti-human gammaglobulin (AHGG). The inter- and intra-assay coefficient of variations were lower (7.4 and 2.2% respectively) using Staph. aureus as compared to that observed with AHGG (10.4 and 4.7% respectively). A highly significant correlation was observed (r = 0.53; n = 71; P < 0.001) between per cent bound radiolabel thyroglobulin in radioassay and log reciprocal titre of ATA by haemagglutination method. Radioassay scored more number of positive sera as compared to haemagglutination method for normal controls (6 vs 1; n = 46) and patients of thyroid diseases (151 vs 70; n = 238). Due to the relatively poor stability of tracer on storage larger inter-assay coefficient of variations were observed with the radiolabelled preparations older than 10-12 days. The radioassay method evaluated is sensitive, reproducible and useful in detecting presence of anti-thyroglobulin autoantibodies. PMID- 1283858 TI - Stimulation of hepatic protein synthesis in response to Mikania cordata root extract in carbon tetrachloride-induced hepatotoxicity in mice. AB - The effect of Mikania Cordata root extract was evaluated on the rate of hepatic protein synthesis in vivo in CCl4-induced liver damage. Pretreatment with the root extract (100 mg/kg, once daily for successive 5 days) showed a marked enhancement in the levels of hepatic DNA, RNA and protein content that were adversely affected with CCl4 treatment in the experimental mice. Increase in the total protein mass, fractional rate of protein synthesis (% of protein synthesized/day), total rate of protein synthesis (fractional rate x protein mass), ribosomal capacity (RNA/protein), ribosomal efficiency (rate/ribosome) and high turnover rate of protein (protein/DNA) in response to the pretreatment of the root extract in hepatic tissue indicated the tissue repair leading to a functional improvement of the hepatocytes that were disorganised with CCl4 intoxication. PMID- 1283859 TI - Effect of fungicides on the production of amylase by Rhizopus oryzae. AB - Seven fungicides (Brassicol), captan, Dithane M-45, Fytolan, Parasan, Sulfex and Thiram) were tested for their effect on the production of amylase enzyme by Rhizopus oryzae. The activity of amylase was determined by cup-plate method. All the fungicides were found inhibitory for the synthesis of amylase. Out of these, Parasan was the most effective causing hundred percent inhibition at 0.025% concentration. No amylase production was recorded when Thiram, Fytolan, Brassicol, Captan and Dithane M-45 were used at 0.5, 1.5, 2.0, 2.0, and 2.0% concentration respectively. Sulfex was found to be less effective, as hundred percent inhibition of amylase production has not been recorded even at 3.0% concentration. PMID- 1283860 TI - Inhibition of nitric oxide synthesis improves survival in a murine peritonitis model of sepsis that is not cured by antibiotics alone. AB - Inhibition of nitric oxide synthesis was investigated in a murine model of advanced sepsis in which antibiotic therapy alone did not improve survival. Seven hours after receiving a lethal intraperitoneal challenge with live Escherichia coli, mice were given either NG-monomethyl-L-arginine (L-NMMA) intravenously, imipenem-cilastatin subcutaneously or a combination of both. L-NMMA (3-300 mg/kg) or imipenem-cilastatin (10 or 50 mg/kg) given alone did not improve survival; co administration of L-NMMA and either 10 or 50 mg imipenem-cilastatin/kg improved survival significantly. These findings suggest that nitric oxide contributes to the morbidity associated with advanced sepsis and that nitric oxide synthase inhibition may improve the efficacy of conventional antimicrobial treatment of severe infections. PMID- 1283861 TI - Effects of a nitric oxide synthase inhibitor on non-cholinergic junction potentials in the circular muscle of the guinea pig ileum. AB - Intracellular microelectrodes were used to record junction potentials from the circular muscle cells of the guinea pig ileum in vitro at 37 degrees C in a modified Krebs solution containing nifedipine (1-2 microM) and hyoscine (1 microM). Transmural nerve stimulation, using volleys of three pulses at 50 Hz, produced a complex response consisting of an inhibitory junction potential (IJP) followed by a prolonged depolarization. Following the addition of the nitric oxide synthase inhibitor NG-nitro-L-arginine (NOLA, 100 microM) the amplitude of the IJP (recorded 10 mm aboral to the stimulating electrodes) was increased by approx. 10% (n = 4). The further addition of apamin (250 nM) abolished the IJP revealing a non-cholinergic excitatory junction potential (EJP). In other experiments (n = 8), preparations were treated with apamin then subjected to substance P desensitization (500 nM, > 20 min). Transmural nerve stimulation now produced a triphasic response (recorded 1 mm aboral to the stimulating electrodes) consisting of: (a) an initial hyperpolarization (approx. 5 mV) lasting about 1 s; followed by (b) a depolarization reaching a peak (approx. 7 mV less negative than the RMP) approx. 2 s after nerve stimulation; and finally (c) a small (approx. 3 mV) hyperpolarization. The addition of NOLA reduced all three phases by 80-90% (n = 8). The subsequent addition of L-arginine (5 mM) partially reversed these effects (n = 3). Conditioning hyperpolarization up to 20 mV increased the amplitude of the NOLA-sensitive IJP and EJP. Further conditioning hyperpolarization reduced the amplitude of the IJP and enhanced the amplitude of the EJP. Large conditioning hyperpolarizations (> 60 mV) reduced the amplitude of both the IJP and EJP. An estimation of the membrane conductance changes occurring during the initial hyperpolarization and depolarization suggest that it was either unchanged or increased. During large conditioning hyperpolarizations in the absence of nerve stimulation, the membrane potential was unstable and began to show spontaneous oscillations (up to 30 mV, every 4-5 s) resembling slow waves. These experiments indicate that NO, or a related compound, appears to mediate the nerve induced apamin-resistant IJP and substance P- and hyoscine resistant EJP in the circular muscle of the guinea pig ileum. PMID- 1283862 TI - Pancreatic enzymes in chronic renal failure and transplant patients. AB - The aim of the present study was to determine the frequency and degree of elevated serum levels of Total Amylase (TA), Pancreatic Amylase (PA), and Lipase (L) activity in patients with chronic renal failure (CRF) on conservative therapy; CRF on periodical hemodialysis (HD); in renal transplant (RT) and in a control Group (C). Mean values were significantly higher in all groups than Group C for TA (p < 0.005), PA (p < 0.0001) and L (p < 0.0001). A statistically significant correlation was found between TA and L vs creatininemia values in CRF patients, but only up to a certain level (creatininemia < 6 mg %) (p < 0.03 and p < 0.05), above which there was no correlation. The enzyme most frequently over the maximum normal limit was PA, both in the total CRF group (51%), in the hemodialysis patients (65%), and in the RT patients (55%); but only a few patients had values two times higher than the normal limits: 15% in the total CRF, 14% is the hemodialysis, and 10% in the RT groups, respectively. These results suggest that the increase in serum pancreatic enzyme during chronic renal pathology is slight but frequently occurs. It is possible that in these patients together with the renal excretion impairment there could also be some subclinical pancreatic damage; its genesis could also depend on the pharmacological treatment used (diuretics, immunosuppressive drugs) commonly adopted in these pathologies. PMID- 1283863 TI - Evaluation of surgical risk in palliation and resection of pancreatic cancer. Perspective study and tables to calculate the risk. AB - High morbidity and mortality rates are reported for bypass and resective surgery of pancreatic cancer. In a retrospective study we correctly predicted the postoperative course in 88% of the patients who underwent bypass surgery and 83% of those who had a resection for pancreatic cancer. Before starting with clinical application of this scoring system, we undertook a prospective study to confirm its predictive value. Sixty-seven consecutive patients with pancreatic cancer were included: 42 patients underwent bypass surgery and 25 pancreatic resections. The operative mortality was 14% for palliative surgery and 0% for resective surgery. Surgical team and nurses were totally unaware of the predicted risk. The preoperative forecast proved to be correct in 81% of bypass surgery and in 88% of resective surgery, although surgical mortality had decreased from 21 to 14% for bypass surgery and from 17 to 0% for resective surgery. Tables are included to calculate the surgical risk for each of 162 combinations of the risk factors considered in the predictive model (81 for bypass surgery and 81 for resective surgery). Calculation of surgical risk is important when evaluating different treatments for pancreatic cancer are available. PMID- 1283864 TI - Histological pancreatitis in end-stage renal disease. AB - To clarify a possible cause of hyperamylasemia in end-stage renal disease (ESRD), histological studies were performed on the pancreatic glands of twenty-seven autopsied patients with ESRD who had received long-term hemodialysis. The findings were compared with those in a similar number of age-matched control subjects. Histological evidence of pancreatitis was found in 51.9% of the ESRD patients as compared with 14.8% in the controls (p < 0.005). The pancreatitis was chronic in nature in 85.7% of the ESRD patients showing changes of pancreatitis. Secretin administration to an additional group of twelve patients with ESRD induced an elevation in the activities of both total and P-type serum amylase in only one patient. These findings suggest that although histological pancreatic alterations are common in patients with ESRD, they are probably not responsible for the P-type hyperamylasemia frequently found in such patients. PMID- 1283865 TI - [Diagnosis of pancreatic neoplasms by analysis of tumor markers and pancreatic enzymes]. PMID- 1283866 TI - [Screening of pancreatic neoplasms (discussion)]. PMID- 1283867 TI - Education and communication: a professional response. PMID- 1283868 TI - "Gray areas" in the final OSHA bloodborne pathogens standard. PMID- 1283869 TI - Infectious diseases in dentistry: answers to ten legal (or illegal?) questions. PMID- 1283870 TI - Update on disinfection of impressions, prostheses, and casts. ADA 1991 guidelines. PMID- 1283871 TI - Pediatric dental patients' perceptions of personal protective equipment. PMID- 1283872 TI - Hepatitis B and available vaccines. PMID- 1283873 TI - A matter of ethics. PMID- 1283874 TI - Dead birds and dead fish. PMID- 1283875 TI - Genetic control of bone remodeling. AB - Biological research related to orthodontics naturally leads to two general areas. One is the investigation of craniofacial growth and development in normal and abnormal circumstances, attempting to understand the etiological basis for the development of malocclusion or dentofacial deformity. The other concerns developing an understanding of the basic mechanisms involved in tooth movement during orthodontic therapy. This paper reviews ongoing research in both areas. PMID- 1283876 TI - Targeted drug delivery. AB - Achieving adequate dosage of a drug to be effective, without crossing the line into toxicity, can be a problem. This paper reviews ongoing research into methods of delivering drugs only to diseased tissue or cells, minimally affecting surrounding tissue. In particular, the author discusses encapsulating drugs in liposomes (artificial phospholipid microcapsules) which will only bind to certain cells. PMID- 1283877 TI - Growth factors in bones and teeth. AB - Human bone contains an abundance of polypeptide growth factors. These growth factors stimulate the proliferation and activity of bone cells and can stimulate bone formation. Data from this laboratory and others suggest that bone growth factors may act to couple bone formation to resorption to maintain bone mass during remodeling. Research is underway to study these growth factors in bones and teeth, and their possible roles in both the pathogenesis and the treatments of osteoporosis and dental diseases. PMID- 1283878 TI - Shape changes due to functional appliances. AB - Functional appliances are now routinely used in orthodontic treatment to correct anteroposterior skeletal discrepancies, based on the assumption that existing functional patterns can be modified to yield a new morphological pattern. However, the mechanisms by which this correction occurs remain in dispute as current measurement procedures, primarily mathematical, do not adequately describe shape changes. This paper introduces a new measurement method, Fourier descriptors, to clinical dentistry. PMID- 1283879 TI - The role of integrin adhesion receptors in gingival wound healing. AB - Integrins, a family of cell adhesion receptors, play an important part in wound healing. These complex macromolecules are defined, and their roles explored. PMID- 1283880 TI - More about HA. PMID- 1283881 TI - HA disagreement. PMID- 1283882 TI - Artists & dentistry through the ages. PMID- 1283883 TI - The literary value of a toothache. PMID- 1283884 TI - Esotropia following posterior superior alveolar nerve block. AB - Adequate use of local anesthetics is an important phase of modern dentistry. Regardless of the care used in administration of local anesthetics, unusual reactions can occur. A case is presented in which posterior superior alveolar administration of two percent Lidocaine 1/100,000 epinephrine resulted in medial rotation of the orbit (esotropia). PMID- 1283885 TI - A life-threatening, spontaneous, periodontitis-induced infective endocarditis. PMID- 1283886 TI - HA conclusions misleading? PMID- 1283887 TI - The effects of adenine and dimethyl sulfoxide on the mouse pancreas. AB - The authors have studied the effects of dimethyl sulfoxide (DMSO) on the plasma alpha-amylase activity in mice that sustained a pancreatic injury induced by an oral administration of adenine. In mice given a 5% solution of DMSO as drinking water for 3 d prior to the administration of adenine (175 mg/kg), and also drank this DMSO solution until the end of the experiment, hyperemia of the pancreas was observed and the level of plasma alpha-amylase activity became significantly higher than the level seen in the control mice. A pathological examination also revealed vacuolation and zymogenic degranulation. Further, the plasma alpha amylase activity level increased only in mice given this 5% DMSO solution, and no increase was noted in mice given a 3% or a 1% DMSO solution for drinking water. Further, the pancreatic lipid peroxide level of mice given this 5% DMSO solution was significantly higher than the level seen in the control group. Based on the above results and associated data, it is thought that an oral administration of adenine can induce a pancreatic injury in the mouse, and that this injury is sustained with the assistance of DMSO. PMID- 1283888 TI - Mexiletine and disopyramide suppress ventricular premature contractions (VPC) irrespective of the relationship between the VPC and the underlying heart rate. AB - The effects of mexiletine (300 mg/day, 24 patients) and disopyramide (300 mg/day, 20 patients) on ventricular premature contractions (VPCs) were studied using a 24 hour ambulatory electrocardiogram. The VPC frequency was evaluated as a function of the underlying heart rate (HR). The VPC-HR correlation was classified into 2 major types, depending on whether the frequency of the VPC increased with the increased HR (positive type) or not (nonpositive type). The effects of the drugs were assessed based on the VPC-HR correlation and on the percent reduction of the VPC frequency. Mexiletine and disopyramide significantly decreased the frequency of the VPCs of both the positive and nonpositive types. Each drug was assumed to be effective when the percent reduction of the VPC frequency exceeded 70%. Mexiletine (300 mg/day) was 58.5% effective in positive type patients and 33.3% effective in nonpositive type patients, with a total efficacy of 45.8%. Disopyramide was effective in 50% of total cases with 44.4% in positive type patients and 54.5% in nonpositive type patients. However, the efficacy of these drugs on the 2 different types of VPCs was the same statistically. The findings strikingly contrasted those obtained with diltiazem and atenolol, which predominantly suppressed VPCs of the positive type which share similar characteristics with a triggered activity in vitro. We conclude that the mode of action of class I antiarrhythmics on the VPCs differs from that of class II or IV antiarrhythmics, as viewed from the VPC-HR relationship, and that the difference probably comes from the different arrhythmogenesis for positive and nonpositive types of VPCs, in addition to the different electrophysiological actions of mexiletine and disopyramide. PMID- 1283889 TI - Assembly of 100 nm periodic fibrils (type VI collagen) in human infant corneal stroma. AB - An experimental model for the age-related changes in the extracellular matrix of the human cornea was developed. Human infant corneal stroma in which no long spacing collagen occurred naturally was treated with 20 mM adenosine triphosphate (ATP). The ATP-treated cornea was observed and compared with nontreated control specimens by electron microscopy. Numerous 100 nm periodic fibrils which resembled long-spacing collagen were formed by the treatment. These experimentally formed fibrils appeared to attract and aggregate the collagen fibrils with D-periodicity, which indicated a connection between type VI and type I collagen. By ruthenium red staining, the cross-bands of the 100 nm periodic fibrils were positively stained, indicating that glycosaminoglycans or proteoglycans were involved in the formation of these fibrils. PMID- 1283890 TI - Effects and distribution of intravitreally or subretinally injected silicone oil identified in rabbit retina using osmium tetroxide method. AB - Silicone oil was injected into the eyes of 28 rabbits. Utilizing the specific affinity of osmium tetroxide for lipids, the pathological features and histochemical localization of silicone oil within the retina were studied. This osmium tetroxide technique makes it possible to identify the presence of silicone oil particles in the ocular tissues. It was demonstrated that in eyes with silicone oil injected into the vitreous cavity or subretinal space, silicone oil was detected in the inner retinal layer and in phagocytes in the vitreous cavity but not in the outer retinal layer, retinal pigment epithelium and choroid. In addition, prominent subretinal and epiretinal proliferation with abundant phagocytes containing silicone oil particles were noted in the eyes with subretinal injection of silicone oil through an artificial retinal break. This study suggests that when injected subretinally silicone oil induces excessive subretinal and epiretinal proliferation. PMID- 1283891 TI - [Landau-Kleffner syndrome]. AB - The Landau-Kleffner syndrome is characterized by the combination of acquired aphasia and epilepsy. Disturbances appear at an age between 2 and 7 years. The prognosis of epilepsy is favourable, but the outcome of aphasia is different. A 15-year old boy is described as one who is totally unable to communicate through speech even 11 years after onset of aphasia. Diagnostics, aetiology, pathophysiology and new therapeutic possibilities of the syndrome are discussed. PMID- 1283892 TI - [The EEG of patients with tetralogy of Fallot with and without hypoxemic seizures]. AB - Electroencephalograms were recorded of 135 children with TOF. They were normal in 51%, slightly disturbed in one-third, and severe disorders were seen in 16% of patients. Although not statistically significant, cyanotic spells tend to be associated with more severe impairment of the bioelectrical brain function. As far as patients develop additional neurological complications, these result in severe electro-encephalographic changes. Thus, electroencephalographic findings suggest early corrective surgery. PMID- 1283893 TI - Castration-like effects on the human prostate of a 5 alpha-reductase inhibitor, finasteride. AB - Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BPH) and prostate cancer. 5 alpha-Reductase deficiency in humans, an experiment of nature, is an uncommon genetically transmitted disorder in which prostate size remains very small throughout adult life. A 5 alpha-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trials in patients with BPH to statistically decrease prostate size and improve clinical symptoms in comparison to placebo controls. In the untreated BPH prostate, tissue levels of dihydrotestosterone (DHT) and testosterone (T) averaged 4.2 and 0.2 ng/g, respectively. Following one week of finasteride therapy, T levels rose to a mean of 1.32 ng/g while DHT levels decreased to 0.62 ng/g. These values contrast with values in prostate tissue from surgical castrates in which DHT and T values average 1.14 ng/g and 0.1 ng/g, respectively. If we use the relative binding affinity of T and DHT to the androgen receptor as a criterion of biological androgen potency, T would appear to be one-fourth as potent as DHT. Using this 1:4 ratio to convert prostatic T to a biologically equivalent amount of prostatic DHT, the total biologically active DHT equivalent in the prostate following one week of finasteride averages 0.95 ng/g compared to a mean of 1.14 ng/g in surgical castrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283894 TI - Chemoprevention strategies for prostate cancer: the role of 5 alpha-reductase inhibitors. AB - Prostate cancer is a major health problem for the aging male population. Despite hormonal dependence, the inevitable emergence of androgen insensitive tumors, which have a dismal prognosis, highlights the need to develop prevention strategies such as chemoprevention. An acceptable agent must interfere with either the process of carcinogenesis or tumor growth, and have minimal toxicity. In clinical studies, 5 alpha-reductase inhibitors have been shown to suppress serum and intraprostatic levels of dihydrotestosterone, an important promoter of prostate cancer, leading to reduction in prostate size and suppression of glandular cell activity as measured by prostate specific antigen secretion. In addition, 5 alpha-reductase inhibitors have demonstrated an excellent safety profile and tolerability in 12 month controlled clinical trials. No significant metabolic effects have been observed in gonadotropin secretion, spermatogenesis, serum lipids or glucose tolerance. The efficacy and safety of 5 alpha-reductase inhibitors in studies to date, combined with the androgen dependence of tumor production, strongly supports investigating their use for chemoprevention of prostate cancer. PMID- 1283895 TI - Prostate-specific antigen and diagnosing early malignancies of the prostate. AB - Prostate-specific antigen is a kallikrein-like serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. Prostate-specific antigen is also present in the serum and can be measured reliably by several different assays. Although the protein is prostate-specific, it is not prostate-cancer-specific. As a result, benign conditions such as benign prostatic hyperplasia, prostatitis and infarction, as well as prostatic intraepithelial neoplasia, can be associated with elevated serum levels of prostate-specific antigen. Approximately 25% of men with benign prostatic hyperplasia have an elevated serum value of prostate specific antigen, whereas 35% to 40% of patients with organ-confined prostate cancer have a level within the reference range. Prostate-specific antigen can identify some cancers not detectable by digital rectal examination; alternatively, this examination can identify cancers not detectable from the serum prostate-specific antigen concentration. Thus, the most complete evaluation of the prostate gland is achieved when both the prostate-specific antigen value and the digital rectal examination are used. The density and the rate of change of serum prostate-specific antigen are new concepts to improve the ability of prostate-specific antigen to detect early prostate cancer. Preliminary results are encouraging, but additional studies are required to determine the true usefulness of these new variables. Thus, in 1992, determination of the prostate specific antigen value is a valuable new tool for the practicing physician and will be instrumental in our campaign to diagnose clinically significant prostate cancer at an early, curable stage. PMID- 1283896 TI - Quantitative morphometric analysis of the microcirculation in prostate carcinoma. AB - Many neoplasms have been shown to induce capillary neovascularization and this may correlate with aggressive behavior. We investigated the phenomenon of neovascularity in benign and malignant prostatic tissue. Microvessel profiles and tissue sections were visualized by antibodies to Factor VIII and standard immunohistochemical techniques, and quantified utilizing the Optimas computerized image analysis system. Microvessel density was compared in benign and cancerous portions of 15 radical prostatectomy specimens. Fourteen of 15 cases demonstrated significantly higher vascular density in the area of carcinoma as compared with benign tissue (ratio = 2.02, p < 0.001). Distribution of microvessels within malignancy was random, whereas it was restricted primarily to the periglandular space in benign tissue. Among 20 men undergoing radical retropubic prostatectomy, there was a correlation between the vessel density and the pathologic stage. No patient with organ-confined carcinoma or cancer penetrating (but not perforating) the capsule had microvessel density greater than 156 microvessels/mm2. In contrast, six of 15 men with more advanced pathologic stage exceeded this arbitrary threshold. These data demonstrate both increased vascularity of prostatic carcinoma as compared with benign tissue, and a further correlation between pathologic stage and vascularity. Microvessel density may be useful as a prognostic indicator. PMID- 1283897 TI - The role of digital rectal examination, transrectal ultrasound, and prostate specific antigen for the detection of confined and clinically relevant prostate cancer. AB - In a study population, can digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) (monoclonal) effectively detect the majority of clinically relevant cancer? If this is possible, the remaining patients could then be considered for chemopreventive protocols. The American Cancer Society/National Prostate Cancer Detection Project (ACS/NPCDP) had a cancer detection rate of 2.4% for its initial year utilizing PSA, DRE and TRUS. TRUS and PSA detected 73% more cancer than DRE alone. TRUS detected a greater percentage of cancers than DRE (85% vs. 64%). PSA was > or = 4 ng/ml for 66% of prostate cancer patients; 11% of cancer patients had PSA < 2 ng/ml. PSA decision levels based on gland volume detected a subgroup at the 95th percentile that had a nine-fold increased risk for cancer. In a separate study differentiating benign prostatic hypertrophy (BPH) and cancer, we found 0.12 +/- 0.13 ng/ml/gm for serum PSA (sPSA)/gm BPH. This study proved that predicted PSA (pPSA) = gland volume x 0.12; this equation also functioned at the 95th percentile for any individual patient. Individual patient assessment: 1. Entry level PSA = 2 ng/ml. 2. Those patients with PSA > 2 ng/ml have TRUS determination of gland volume (performed by technician). 3. pPSA = gland volume x 0.12. If sPSA > pPSA then: 4. (sPSA-pPSA)/2 = predicted volume (cc) of cancer; 5. 3 square root of volume of cancer = mean diameter (cm) of cancer. Thus, these results should detect the majority of clinically relevant cancer (> 0.5 cc). PSA combined with TRUS and DRE can identify high risk groups for cancer. PMID- 1283898 TI - A retrospective analysis of immunohistochemical staining in identification of poorly differentiated round cell and spindle cell tumors--results, reagents and costs. AB - Immunohistochemistry has rapidly established a significant role in diagnostic pathology. We use immunohistochemistry as an adjunct to morphological diagnosis and employ a "panel approach" to the classification of poorly differentiated tumors. This retrospective analysis was conducted to examine the efficacy of such an approach, using, as an example, the two most common categories of poorly differentiated tumors, namely, the poorly differentiated round cell tumors and spindle cell tumors. Five hundred and fifty-seven consecutive cases of such tumors, collected over a two-yr period, had been subjected to immunohistochemical staining because specific or definitive categorization of the tumor was not possible on the basis of the examination of hematoxylin and eosin stained sections. The clinical history, gross and microscopic findings, as well as the results of immunohistochemical stains were analyzed. Immunohistochemistry allowed a definitive diagnosis to be assigned in 420 cases (75.4%). It was particularly useful in identifying malignant melanoma of both epithelioid and spindle types and distinguished between melanoma, lymphoma and poorly differentiated carcinoma in 126 cases of such lesions occurring in adult lymph nodes. It was also useful in identifying tumors in small biopsies where poor cytomorphological preservation or small size precluded accurate categorization. The application of appropriately chosen panels of antibodies tailored to a narrow list of differential diagnoses helped to identify myogenous, vascular, nerve sheath and fibrocystic lesions among the group of spindle cell tumors. Immunohistochemistry provided definitive diagnoses in 70% of round cell tumors and 92% of spindle cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283899 TI - Rare earth metal ions for unprecedentedly fast RNA hydrolysis. AB - Adenylyl(3'-5')adenosine (ApA) and uridyl(3'-5')uridine (UpU) are hydrolyzed at unprecedentedly large rates by rare earth metal ions at pH 8, 30 degrees C. With 0.01 M Tm(III), the half-lives are 10 min and 51 min, respectively. Potentiality of these ions as catalytic center of artificial ribonuclease is proposed. PMID- 1283900 TI - Stability difference between DNA and RNA mini-hairpins containing two G-C pairs. AB - The deoxyribonucleotide fragments, d(GCGAAAGC) and d(GCGAAGC) form extraordinarily stable mini-hairpin structures containing only two G-C pairs. In contrast, the corresponding ribonucleotide fragments, r(GCGAAAGC) and r(GCGAAGC) are not so stable, although they also form mini-hairpin structures. The stability difference between these DNA and RNA mini-hairpins was examined by NMR studies and the molecular mechanics calculations, and by comparing with the stability of several sequence variants. Their stability was deduced to vary delicately depending on helical patterns formed by DNA (B form) and RNA (A form) structures. PMID- 1283901 TI - Properties of hammerhead-type RNA enzyme derivatives which contain a G-to-I replacement in the loop region. AB - Three hammerhead-type ribozyme derivatives containing a G-to-I replacement in the loop regions were chemically synthesized and their properties were examined. All three complexes showed a markedly reduced RNA-cleaving activity. NMR studies suggested that the complex with mutation at the third guanosine of the longer internal loop region has the greatest influence on the conformation of the loop regions. PMID- 1283902 TI - 15N and 13C labeling of Escherichia coli tRNAs toward the NMR analysis. AB - Escherichia coli tRNAs were labeled with stable isotope 15N in vivo. Three species of tRNA, tRNA(Glu), tRNA(Lys) and tRNA(Ile), were purified by an HPLC system and their NMR spectra were observed. In heteronuclear 1H-15N multiple or single quantum coherence (HMQC or HSQC) spectra, the crosspeaks corresponding to NH3 of U and NH1 of G can be distinguished clearly since their 15N chemical shifts are significantly different from each other. Thus, this combination of 15N labeling and the proton detected heteronuclear experiments are useful for the signal assignment and the conformational analysis of tRNAs. Furthermore, C1'- selective 13C-labeling of nucleotides was examined in vivo in order to resolve the H1' signals of tRNAs. By using a newly constructed E. coli mutant strain, the isotopic enrichments of more than 90% at C1' and of less than 10% for other ribose carbons were achieved. PMID- 1283903 TI - In vitro study of E. coli tRNA identity elements. AB - Various tRNA transcripts were constructed to study the identity elements of E. coli tRNAs (Arg, Lys, Ala, Trp, Thr, Gly, Ser, Asn, Cys, His). Anticodon are involved in the identity elements in these tRNA species except the case of tRNA(Ala) and tRNA(Ser). Especially, the second and third positions of the anticodon are the recognition sites of E. coli tRNA(Arg), tRNA(Lys) and tRNA(Thr) for their cognate aminoacyl-tRNA synthetases. Discriminator base is an identity determinant of the above examined tRNAs except tRNA(Thr) and tRNA(Ser). In some cases, acceptor stem (Thr, Gly, His) and variable pocket (Arg, Ala) are considered to be the recognition elements. PMID- 1283904 TI - Evolution from semi-tRNA to tRNAs, rRNAs and an early peptide-synthesizing RNA molecule. AB - tRNA was found to have emerged by tandem duplication of a ca. 37-base RNA ("semi tRNA"). The most ancestral anticodon was "(5')CCA(3')". The peptidyltransferase (PT) region of 23S rRNA was concluded to be a 5S rRNA homologue. Important evidences were obtained for elucidating that the RNA transcript from the Bacillus subtilis (BSU) trrnD operon is a relic of an early peptide-synthesizing ribozyme. PMID- 1283905 TI - Substitution of non-catalytic stem and loop regions of hammerhead ribozyme with DNA counterparts only increases KM without sacrificing the catalytic step (kcat): a way to improve substrate-specificity. AB - In elucidating structure-function relationships and stabilizing ribozymes in vivo, several chimeric RNA/DNA ribozymes and substrates were chemically synthesized. Measurements of kinetic parameters revealed that the maximally deoxyribonucleotide-substituted ribozyme (DRDRD32) gained the highest catalytic activity reaching the kcat value of > 10 min-1, the highest value ever reported for hammerhead-type ribozymes. Since these chimeric ribozymes are more stable than the wild-type all-RNA ribozymes in vivo and they also possess higher substrate-specificity, they are considered to be better candidates for antiviral therapeutic agents. PMID- 1283906 TI - Inhibitory effects of 2'-deoxy-5-styryluridine 5'-triphosphate analogs on retroviral reverse transcriptase and eukaryotic DNA polymerases. AB - Some sugar modified analogs of 2'-deoxy-E-5-styryluridine triphosphates were synthesized and examined for their inhibitory effects on eukaryotic DNA polymerases and HIV-1 reverse transcriptase. Among these compounds, 3'-azido 2',3'-dideoxy-E-5-styrylUTP (6) and 2',3'-dideoxy-E-5-styrylUTP (7) showed remarkable inhibitory effects on reverse transcriptase. The mode of action and the influence of the substituent at C-5 of 2',3'-dideoxyUTP analogs will be described. PMID- 1283907 TI - The 6-azauridine analogues possessing sedative and hypnotic effects. AB - Pharmacological effects of 6-azauridine (4) analogues were evaluated using hypnotic activity, pentobarbital (PB)-induced sleep prolongation and locomotor activity as indices. Compound 4, N3-benzyl- (10), N3-o-xylyl- (11), N3-m-xylyl- (12), N3-p-xylyl- (13), N3-alpha-phenylethyl-substituted 6-azauridine (14) exhibited hypnotic activity and PB-induced sleep prolongation, whereas N3-alkyl substituted analogues (methyl-, ethyl-, n-propyl-, n-butyl- and allyl substitution) did not. Compound 4 and xylyl analogues (11-13) significantly decreased locomotor activity of mice by i.c.v. injection and produced motor incoordination. The results indicate that 4 and its benzyl related analogues, but not alkyl analogues have depressant effects on the central nervous system (CNS). PMID- 1283908 TI - RNA-RNA and RNA-DNA ligation with the sTobRV(+) hammerhead ribozyme. AB - The sTobRV(+) ribozyme consists of a small catalytic domain and two wing sequences(1). By changing its wing sequences, the ribozyme can cleave many different RNAs in a site-specific manner, functioning as an RNA restriction enzyme(1). Although relatively strong ligase activity is known to be associated with sTobRV(+) RNA(2,3), the sTobRV(+) ribozyme itself has been claimed to have no ligase activity. Here, we show the evidence that the sTobRV(+) ribozyme has the ability to rejoin its digestion products at low temperatures such as 4 degrees C. In contrast, little or no ligation product can be produced at 50 degrees C, the temperature giving the maximum digestion activity. The ligation reaction requires Mg++ ion. The first substrate (P1, see Fig.1), possessing 2',3' cyclic phosphate, must be RNA, but the second substrate (P2), required to have 5'OH, can be replaced by DNA counterparts, equal to or longer than dimer, thus making it possible to generate RNA-DNA chimeric molecules. We also show the resultant RNA-DNA chimera to be digestable by the sTobRV(+) ribozyme. RNase digestion indicates the phosphodiester linkage thus generated to be exclusively 3'-5'. PMID- 1283909 TI - Application of L-DNA to the study of the specific DNA recognition mechanism of bleomycin. AB - The hexadeoxynucleotide analog, L-d(CGCGCG) composed of L-deoxyribose was synthesized and clearly shown to have the same conformation and dynamic properties with natural D-d(CGCGCG) except for chirality with CD spectra. This unnatural hexanucleotide was not cleaved by bleomycin, an antitumor DNA cleaving drug, but was able to bind to the DNA binding domain of bleomycin to a similar extent with the natural one. These results strongly suggest the importance of the other moiety than the DNA binding domain for the specific DNA recognition of bleomycin. Thus, L-oligonucleotides are useful for the study of DNA-drug interactions. PMID- 1283910 TI - Does RNA hydrolysis involve rate-limiting formation of the pentacoordinate intermediate or rate-limiting decomposition? Phenyl ester of adenosine 3' phosphate as a novel probe. AB - The rate-limiting step of enzymatic and non-enzymatic hydrolysis of RNA has been experimentally determined by use of phenyl ester of adenosine 3'-phosphate as a novel probe. Alkaline hydrolysis of RNA involves rate-limiting decomposition of a pentacoordinate intermediate, and any catalyst, either enzymatic or non enzymatic, should promote the decomposition step. PMID- 1283911 TI - Cross-ligation and exchange reaction of RNA catalyzed by hairpin ribozymes. AB - The catalytic domain in the minus strand of the satellite RNA of tobacco ringspot virus (sTobRV(-)) assumes a hairpin-like secondary structure. This ribozyme catalyzes a cross-ligation reaction between substrate RNAs of different lengths. We constructed ribozymes to probe the activities of ligation and RNA fragment exchange. PMID- 1283912 TI - OligoDNA-oligoamine hybrid for facile and sequence selective hydrolysis of RNA. AB - Oligoamines as catalytic sites for RNA hydrolysis are attached to 5'-end of [dT]16 using urethane bond. The [dT]16-pentaethylenehexamine hybrid promptly hydrolyzes poly[A] at pH 8, 50 degrees C. Definite importance of the complexation between the poly[A] and the [dT]16 moiety is confirmed by a marginal hydrolysis of poly[C]. Hydrolytic catalysis is ascribed to intramolecular acid-base cooperation of two or more amino residues in the oligoamines. PMID- 1283913 TI - High-performance separation of polynucleotides by capillary gel electrophoresis. AB - Capillary gel electrophoresis was applied to the high speed separation of DNA and RNA. Factors affecting resolution and speed were optimized for the single base resolution of polynucleotides. Polynucleotides up to 350 bases were completely resolved within 38 min under optimum conditions. PMID- 1283914 TI - Characterization of four-stranded DNA and RNA fragments. AB - We have investigated the structures formed by deoxyribo- and ribooligonucleotides containing guanine-rich sequences. Inter- and intrastrand guanine tetrads are not only more stable in the presence of K+ than they are in the presence of Na+, but also more compact. PMID- 1283915 TI - Kinetic studies of the interaction of synthetic RNAs with quinacrine and its analogs. AB - Temperature-jump relaxation method has been used to study the interaction of synthetic RNAs with quinacrine (QAC) and its analog. Two relaxation times were observed. The dependence of relaxation times on the RNA concentration and optical properties of the RNA-dye complexes suggests that (1) QAC binds to poly (rA).poly(rU) through two bimolecular reactions including isomerization from one complex form to another and (2) the 2-methoxy group of the acridine ring plays a significant role in the isomerization. PMID- 1283916 TI - Conformational features of the four successive non-Watson-Crick base pairs in RNA duplex. AB - A tridecaribonucleotide, r(UGAGCUUCGGCUC) doesn't form hairpin or interior loop and forms a double helix of 12 base pairs including the four successive nonstandard base pairs, U.G-U.C-C.U-G.U, in the crystal. Non-Watson-Crick base pairs, G.U and U.C are nicely incorporated in RNA duplex maintaining the regular A-form backbone. There exist the good overlapping between base pairings, U.G and U.C, so as to stabilize the nonstandard base pair track. Hydrogen bond networks involving water molecules in the major and minor grooves to stabilize this mismatch base pairing array, are observed and its conformational features are described. PMID- 1283917 TI - Fluorescence resonance energy transfer between specific-labeled sites on DNA. AB - Fluorescence resonance energy transfer on DNA has been studied for the estimation of distances between specific sites. Two kind of fluorophores, donor and acceptor, were incorporated on double-stranded DNA via phosphorothioate linkage (Sp, Rp, or racemic mixture). The thermal stability of labeled DNA's was slightly dependent on the stereochemical orientation of fluorophore, however all of the duplex structures were stable under the conditions for fluorescence study. The distances between donor and acceptor fluorophores, estimated from fluorescence energy transfer, generally agreed with the expected distance in a B-type DNA for the limiting distance. PMID- 1283918 TI - Spectroscopic studies of the interaction of synthetic RNAs with quinacrine and its analogs. AB - The interaction of synthetic RNAs with quinacrine (QAC) and its analogs has been studied by absorption, fluorescence and circular dichroism (CD) measurements. The results indicate that the 2-methoxy group of the acridine ring plays an important role in the appearance of the new absorption band upon binding of QAC to poly (rA).poly(rU). PMID- 1283919 TI - Origin of sequence specific cleavage of DNA by bleomycins. AB - A new DNA photocleaving agent which contains bleomycin A2's DNA binding portion and its mono- and terthiazole analogues have been designed and synthesized, and their DNA binding mode and cleavage base specificity have been studied. The photoactive p-nitrobenzoyl group attached at the end of molecules cleaves DNA on UV irradiation. All the oligo-thiazole compounds exhibited high sequence specificity in DNA scission. The bithiazole derivative did not cleave DNA at or near 5'-GpT-3' or 5'-GpC-3' as expected from widely believed DNA binding mechanism of the antibiotics. PMID- 1283920 TI - [Lipid peroxidation and proteinase inhibitors in experimental osteoarticular tuberculosis]. AB - Changes in lipid peroxidation parameters (LP), antioxidant system and proteinase inhibitors were studied at different evolutionary stages of experimental osteoarticular tuberculosis in 30 rabbits. All stages of the process were characterized by LP activation which in animals of all groups (except rabbits having the acute stage of arthritis) is accompanied by compensatory increase of superoxide dismutase and ceruloplasmin activity. Deficiency of superoxide dismutase found in the acute stage of arthritis with a growth of LP activity shows its inadequate production at a given stage of articular inflammation. Decrease in alpha 1-proteinase inhibitor activity at the stage of osteitis with reactive synovitis can be caused by the influence of LP products. The importance of this mechanism in the inhibition of alpha 1-proteinase inhibitor, together with reduction in its production at the acute stage of arthritis, cannot be ignored. The results obtained make it possible to recommend further study of the perspectives of antioxidants use in osteoarticular tuberculosis. PMID- 1283921 TI - Therapeutic imagery enhanced by hypnosis. AB - This paper has reviewed the history of using imagery as a powerful change and healing agent in humans. It has been a rather underused technique in the practice of Western medicine and psychiatry. I hope that the specific examples and techniques described herein will stimulate and motivate the reader to adopt them in their clinical practice and creatively develop new strategies and techniques applicable in other fields such as sports, the arts, education, and the human life cycle. PMID- 1283922 TI - Autoradiographic localization of 125I-galanin binding sites in the blowfly brain. AB - The localization of porcine galanin (pGAL) binding sites in the brain of the blowfly Phormia terraenovae was investigated by autoradiography using the following radioiodinated ligands: pGAL 1-29 (two isoforms), pGAL 15-29 and rat (r) GAL 1-29. The different porcine radioligands bound specifically with the following intensity: 125I-[Tyr26]-pGAL15-29 > > 125I-[Tyr26]-pGAL1-29 > > 125I [Tyr9]-pGAL1-29. With rat galanin 125I-[Tyr9]-rGAL1-29 no specific binding could be shown. In addition, displacement of 125I-[Tyr26]-pGAL1-29 was tested with pGAL 1-29, pGAL 1-22 and pGAL 15-29 (at 0.1 nM-1 microM). A gradual displacement was achieved with increasing concentrations of pGAL 1-29 and pGAL15-29, whereas no displacement with pGAL 1-22 was detected. The results indicate that the C terminal portion of pGAL is important for binding in the blowfly. The pGAL binding sites were localized in synaptic neuropils of the central body, the antennal lobes, the optic lobes, the pars intercerebralis and the subesophageal ganglion, all of which contain GAL-like immunoreactive neural processes. PMID- 1283923 TI - Tolerance induction to an alloepitope involves antibodies interacting with the T cells activated by the alloepitope. AB - Hyperimmunization of BALB/c mothers with Ab1 (BALB/c anti-C57BL/6) antibody can alter the T-cell repertoire of the syngeneic offspring called BALB/c-p-Ab1. The latter are rendered tolerant to specific alloantigens and are therefore resistant to graft-versus-host disease (GVHD), when challenged 24-48 hours after birth with allogeneic spleen cells. These offspring appear to express cell structures recognized by hyperimmunized mothers and which are presumably the T-cell counterparts of Ab2. Our data suggest that tolerance induction in our mouse model may be modulated by an idiotype network acting during foetal life. The factor modifying the foetal cell repertoire is identified as Ab2 (BALB/c anti-Ab1) antibody transplacentally transmitted from mother to foetus, which seems to carry an "image" of the GVHD-inducing alloepitope and can induce a "GVHD-like" syndrome when passively injected intraperitoneally in normal BALB/c newborn mice. PMID- 1283924 TI - Expression of decay-accelerating factor on synovial lining cells in inflammatory and degenerative arthritides. AB - The decay-accelerating factor (DAF) is a complement regulatory cell surface protein that protects cells from complement-mediated lysis. We analysed synovial tissue biopsies from patients with chronic arthritides for the presence of DAF using immunohistochemistry. DAF was expressed in the synovial lining cell layer both in rheumatoid arthritis (RA) and in osteoarthritis (OA). DAF was also on vascular endothelial cells of synovial tissue. A significant correlation was found between the expression of DAF and of HLA-DR in the lining layer, suggesting that DAF may be induced during a local inflammatory response. In addition, C5b-9 terminal complement complexes were found in several DAF-positive cases, suggesting that complement activation might, in itself, induce DAF expression. We propose that the occurrence of DAF may represent a physiological mechanism for local complement regulation in synovial tissue. PMID- 1283925 TI - Expression of a novel family of epitopes on small intestinal mucins in colorectal cancers, adjacent and remote mucosa. AB - We describe the production, immunochemical and immunohistochemical characterization of monoclonal antibodies (MAbs) raised against the oncofetal small intestinal mucin antigen (SIMA). Four MAbs, reacting with distinct neuraminidase-sensitive SIMA epitopes, were shown to define a novel differentiation-associated relationship of SIMA epitopes within the normal small intestinal villus. Using Swiss rolls of 15 entire colorectal cancer resections, inappropriate expression of SIMA epitopes was detected in all cancers, in adjacent transitional mucosa and remote morphologically normal mucosa, extending as far as resection margins (73%). SIMA expression, whether preexisting or reactive to the tumor, may predispose to malignant change and tumor recurrence. PMID- 1283926 TI - Expression of MUC1 and MUC2 mucins by human tumor cell lines. AB - The secretion and nature of mucins produced from a panel of recently available new gastric and colon carcinoma cell lines (LIM1839, LIM1215, LIM1863, LIM1899, LIM2099, LIM2405, LIM2408, LIM2412, LIM2463), as well as other colon (LS174T, HT29, HT29-SB, COLO533, COLO206), breast (T47D, MCF-7, BT20, ZR75-1) and ovarian (COLO316) tumor cell lines, was investigated. ELISA and Western blotting of the culture supernatants with novel anti-MUC1 and anti-MUC2 monoclonal antibodies (MAbs) specific for mucin core proteins showed their secretion by most of these cell lines. In addition, mucins produced by these cell lines expressed the tumor associated carbohydrate detected by MAb 3E1.2 (glycolylsialyl-Tn, mammary serum antigen or MSA) and the Tn or T antigens reactive with lectin SSA-M. SSA-M detected MUC1 or MUC2 captured by MAbs BC2 or CCP58, while 3E1.2 only detected MUC1-associated carbohydrate, indicating that the MAb may react with a conformationally dependent epitope, or that the sialyl/glycolyl-transferases involved in MSA production may be sequence specific. In addition, the BC2/SSA-M and CCP58/SSA-M assays detected mucins in some samples which were not detected by BC2/BC2 or CCP58/CCP58 dual determinant assays, indicating that this format may be more appropriate for the detection of tumor-associated mucins in body fluids. These new cell lines and assays should be of use in the investigation of mucin core proteins, particularly LIM2463 and LIM1839 which express significant quantities of both MUC1 and MUC2. PMID- 1283927 TI - Determination of optimum cutoff levels of plasma des-gamma-carboxy prothrombin and serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma using receiver operating characteristic curves. AB - Optimum cutoff levels for plasma des-gamma-carboxy (abnormal) prothrombin (DCP) and serum alpha-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases. PMID- 1283929 TI - A microcorrosion cast study for analyzing a new method of indirect myocardial revascularization. AB - In order to study the process of angiogenesis a free skeletal muscle flap was transplanted onto the myocardium of the dog. A microvascular anastomosis with the internal mammary artery (IMA) provided the blood flow to the free graft. In 6 dogs, a myocardial infarction of the anterior wall was induced in order to produce a tissue injury. Four weeks later the skeletal muscle flap was transplanted onto the area of infarction in two dogs with its pars anterior in contact with the heart. In two dogs, the muscle was grafted with its pars posterior, i.e. the muscle fascia between the heart and the graft. In two other dogs, the flap was transplanted with its pars anterior in contact with the heart onto a healthy myocardium. Two animals with infarction were left as controls. Eighteen weeks later a microcorrosion cast was prepared from the hearts with the muscle flap. This evidenced neoangiogenesis in the heart only after transplantation of the graft with its pars anterior onto the myocardium whether it was ischemic or not. The intact muscle fascia, though, inhibited sprouting of vessels. In the controls no angiogenic activity was noted. Results are discussed with regard to the probable origin of the neovessels. PMID- 1283928 TI - Immunohistochemical detection of double-stranded-RNA-dependent protein kinase (p68) with a novel monoclonal antibody TJ4C4. A case report of an AIDS-associated Kaposi's sarcoma treated with alpha-interferon. AB - Double-stranded RNA (dsRNA)-dependent protein kinase (p68) has been shown to be induced by alpha-interferon (IFN-alpha) in mammalian cells. It binds to dsRNA, and is believed to be a factor in the control of both cellular and viral protein synthesis. This report describes the use of a new monoclonal antibody (MAb) TJ4C4, to monitor levels of p68 in a patient with AIDS-associated Kaposi's sarcoma. Using a novel immunoperoxidase/iron staining method, we examined formalin-fixed, paraffin-embedded biopsies prior to, and 4 months after the initiation of IFN therapy. Immunostaining showed low levels (1+ staining) of p68 in the pretreatment tissue, whereas a marked increase (4+ staining) was noted during interferon treatment. This staining suggests an increased level of intracellular p68 expression. This patient has subsequently remained on IFN-alpha therapy and is alive with no evidence of Kaposi's sarcoma, 6 1/2 years after diagnosis. The use of MAb TJ4C4 will greatly facilitate the study of p68 kinase in clinical tissues, and may provide a way to monitor the effects of IFN therapy. PMID- 1283930 TI - Paraganglioma metastatic to the kidney: diagnosis by computed tomography-guided Biopty gun and special stains. PMID- 1283931 TI - [Effectiveness of local prostaglandin instillations in tubal pregnancy in relation to preoperative beta-HCG level]. AB - 33 patients with tubal pregnancy and beta-HCG level less than 2500 mIU/ml were treated with local, laparoscopic Prostaglandin-injection. Re-operation was not necessary and beta-HCG fell to undetectable levels in 73% (p = 0.05). Serial beta HCG correlated poorly with outcome. In patients with an increasing beta-HCG success was limited to 55% (p = 0.59). In contrast patients with falling or stable beta-HCG values had success rates of 85.7% (p = 0.22) and 83.5% (p = 0.30) respectively. Our data suggests there may be a clinical advantage to the use of prostaglandin-injection for the conservative management of early ectopic pregnancy. However the utility of preoperative serial beta-HCG values in predicting success showed a trend, without reaching statistical significance. PMID- 1283932 TI - [Value of experimental and clinical methods on the effectiveness and side effect profile of anti-arrhythmia agents]. AB - The suppression by antiarrhythmic drugs of ventricular premature beats, pairs and salvos is frequently not associated with a suppression of ventricular tachycardia or fibrillation in the same patient. The evaluation of antiarrhythmic drugs must therefore distinguish between antiectopic, anti-reentry and anti-fibrillatory efficacy. Clinical methods such as Holter monitoring and programmed electrical stimulation which only allow the validation of anti-ectopic or anti-reentry efficacy present a major problem in the evaluation of antiarrhythmic drugs. Anti fibrillatory drug efficacy cannot be evaluated by clinical methods. PMID- 1283933 TI - [Combination anti-arrhythmic drug therapy]. AB - Antiarrhythmic treatment with single agents is often ineffective and can be limited by dose-dependent side-effects. Therefore, combinations of antiarrhythmic drugs in smaller and well-tolerated doses are advocated in cases refractory to single antiarrhythmic drugs. Basically, substances belonging to the same electrophysiologic class should not be combined. A combination of beta adrenoreceptor blockers with class I antiarrhythmic drugs may be effective, mainly in cases in which the arrhythmia is dependent on adrenergic stimulation. As shown in our study, the combination of class III and I B-substances can be useful in some cases, from the electrophysiological and clinical points of view. Among the successful combinations of this type are amiodarone and mexiletine, sotalol and mexiletine, and sotalol and tocainide. In patients refractory to amiodarone alone or to a combination with mexiletine, the combined treatment with amiodarone and class-I-C drugs such as flecainide and encainide prolongs the cycle length of ventricular tachycardia, but does not suppress induction of ventricular tachycardia during programmed stimulation. Combination therapy with amiodarone and encainide is associated with a remarkable incidence of proarrhythmic effects. Nevertheless, a combination of antiarrhythmic drugs improves efficacy of therapy in selected patients. However, a close monitoring is mandatory because of the risk of proarrhythmia. PMID- 1283934 TI - [Autoantibodies against the beta 1-adrenergic receptor in myocarditis and dilated cardiomyopathy: localization of two epitopes]. AB - Sera of patients with myocarditis and dilated cardiomyopathy contain stimulatory autoantibodies directed specifically against the beta 1-adrenergic receptor. The binding of the antibodies could be localized to either the first or the second extracellular loop of the beta 1-adrenoceptor. In 73% of the cases investigated the antibodies recognized the second extracellular loop. The agonistic effects of the antibodies were abolished by beta-adrenergic antagonists. Furthermore, the antagonists were able to remove the antibodies from their binding sites. PMID- 1283935 TI - An unusual cause of factitious mineralocorticoid excess. AB - The presence of hypokalaemia in hypertensive patient must prompt a search for increased mineralocorticoid activity. We describe and discuss the observation of a patient with biological markers of hypermineralocorticoidism, despite low plasma and urinary aldosterone levels, and suppressed plasma renin activity. This typical syndrome of apparent mineralocorticoid excess was secondary, in our patient, to prolonged administration of a mineralocorticoid-containing nasal spray. PMID- 1283936 TI - Alpha-fetoprotein-producing immature mediastinal teratoma showing rapid and massive recurrent growth in an adult. AB - A case of immature mediastinal teratoma in a 43-year-old Japanese man is reported. The tumor, which was multicystic with solid zones and measured 12 x 6 x 8 cm, arose in the anterior mediastinum. The serum alpha-fetoprotein (AFP) level was elevated to 5,114 ng/ml before surgery. Histologically, the solid zones showed an admixture of irregular glands lined by columnar or cuboidal epithelium set in a spindle cell stroma, some foci of primitive neural tissue, and scattered small nests of hepatoid cells. Immunohistochemically, the hepatoid cells and epithelia lining some of the cysts showed a strongly positive reaction for AFP. Eight months after surgery, the patient died of respiratory failure caused by a rapidly growing massive recurrent tumor, which measured 40 x 24 x 13 cm, in the left thoracic cavity. However, the elevated serum AFP level had been decreasing during the course of the recurrence in response to chemotherapy. The recurrent tumor showed remarkable proliferation of loose mesenchymal tissue without primitive neural tissue. These findings suggest that immature mediastinal teratoma in adults is highly malignant, and that non-AFP-producing mesenchymal tissue played a critical role in forming the rapidly growing massive recurrent tumor in the present case. PMID- 1283937 TI - [Effect of thyroxine on lung maturation in rabbit fetuses]. AB - The material comprised 11 pregnant rabbits and 95 fetuses stemming from these rabbits. On the 27-th day of pregnancy laparotomy was performed and 1 microgram of thyroxin was administered to the amniotic sac of each fetus in one uterine horn. The fetuses in the second uterine horn, considered as control group, received 0.9% NaCl into their amniotic sac. On the 28-th day cesarean section was carried out, the fluid was collected, the fetuses were taken out, they were weighed and after the lapse of 45 minutes sacrificed by decapitation. The isolated lungs of the fetuses and the amniotic fluid provided the material for further studies. In the amniotic fluid, the content of lecithin and sphingomyelin was determined by thin-layer chromatography. The lungs of fetuses furnished material being used for accomplishing the following types of investigations: determination of mass weight of the wet lungs, and lungs mass after drying, biochemical examination--lecithin and sphingomyelin content in lung homogenates by thin-layer chromatography; histological examination: hematoxylin and eosin stainings by PAS method, argentation by Perdrau method, oil red, toluidine blue stainings as well as electron microscope examination. It has been disclosed that thyroxin administered into the amniotic sac accelerates the fetal lung maturation in rabbits, expressed by higher content of lecithin and by higher ratio of lecithin to sphyngomyelin in fetal lung homogenates at biochemical examinations; it exerts positive effect on the body mass of fetuses and the fetal lung mass, but it fails to influence the lung hydration degree, the sphyngomyelin content in lung homogenates as well as the content of lecithin in the amniotic fluid. The results of histological examination under light microscope have revealed that the lungs of rabbit fetuses in thyroxin group displayed in 70% morphological maturation. The fetal lungs from the control group hardly in 21.1% showed complete maturation. In electron microscopy the fetal lungs in thyroxin group demonstrated more advanced maturation than in the control group, the interalveolar septa were constructed of smaller number of cells, there was a larger number of mature pneumocytes of II type with more abundant lamellar structures, in the alveolar lumen the surfactant appeared markedly more profusely. PMID- 1283939 TI - [Seasonal fluctuations of substance P and vasoactive intestinal peptide concentrations in nasal secretions of patients with nasal allergy to Japanese cedar pollen]. AB - Substance P (SP) and vasoactive intestinal peptide (VIP) concentrations in nasal secretions and plasma from patients with nasal allergy to Japanese cedar pollen and healthy volunteers were measured from Jan to Dec, 1991 using EIA established by us. Simultaneously, the numbers of airborne pollens of Japanese cedar and cypress were counted, and the relation to the SP and VIP concentrations in nasal secretions from the patients with nasal allergy to Japanese cedar pollen was studied. The mean SP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 81.9 +/- 48.4 fmol/mg protein, which was significantly higher than that in the non pollination season (30.4 +/- 14.7 fmol/mg protein) (p < 0.01). Likewise, the mean VIP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 14.2 +/- 10.4 fmol/ml protein, which was significantly higher than that in the non-pollination season (4.2 +/- 3.0 fmol/mg protein) (p < 0.01). The SP and VIP concentrations in nasal secretions from the healthy volunteers were not affected by the scattering of pollens. The SP and VIP concentrations in plasma from the patients and the healthy volunteers were not affected by the scattering of pollens. PMID- 1283938 TI - Oxidative destruction of biomolecules by gasoline engine exhaust products and detoxifying effects of the three-way catalytic converter. AB - Aqueous solutions of engine exhaust condensation products were derived from cars powered by diesel or four-stroke gasoline engines (with and without three-way catalytic converter). The cars were operated on a static test platform. Samples of the different exhaust solutions accumulated in a Grimmer-type distillation trap (VDI 3872) during standard test programs (Federal Test Procedure) were incubated with important biomolecules. As indicators of reactive oxygen species or oxidative destruction, ascorbic acid, cysteine, glutathione, serum albumin, the enzymes glycerinaldehyde phosphate dehydrogenase and xanthine oxidase, and the oxygen free-radical indicator keto-methylthiobutyrate were used. During and after the incubations, oxygen activation (consumption) and oxidative destruction were determined. Comparison of the oxidative activities of the different types of exhaust condensates clearly showed that the exhaust condensate derived from the four-stroke car equipped with a three-way catalytic converter exhibited by far the lowest oxidative and destructive power. PMID- 1283940 TI - Modulation of gastric mucosal calcium channel activity by sucralfate. AB - A gastric mucosal calcium channel complex was isolated from solubilized epithelial cell membranes by affinity chromatography on wheat germ agglutinin. The complex following reconstitution into phosphatidylcholine vesicles exhibited an active 45Ca2+ uptake and responded to calcium channel activator, BAY K8644, and the antagonist, PN200-110. The uptake of 45Ca2+ was inhibited by an antiulcer agent, sucralfate, which at 100 micrograms/ml evoked maximal inhibitory effect of 52%. The channel complex on epidermal growth factor (EGF) binding in the presence of ATP showed an increase in tyrosine phosphorylation of 55 and 170kDa proteins, and the vesicles containing the phosphorylated channels displayed a 48% greater 45Ca2+ uptake. The phosphorylation process was inhibited by sucralfate, which also interfered with the binding of EGF to calcium channel protein. The results indicate that sucralfate has the ability to protect the cellular integrity from calcium imbalance. PMID- 1283941 TI - [Control of anesthetic vapors pollution using a closed circuit apparatus: efficiency and limitations]. PMID- 1283942 TI - [Evaluation of the bactericidal activity of a new disinfectant (Virkon)]. PMID- 1283943 TI - [Control of an automatic apparatus for the sterilization of medico-surgical endoscopes]. PMID- 1283944 TI - [The smoking habit: influence of social factors in an urban area and in a rural area]. PMID- 1283945 TI - [Animal bites in the city of Cagliari, 1985-1989]. PMID- 1283946 TI - [Control of the diffusion of viral hepatitis in detention and penal institutions: a problem not to be underrated]. PMID- 1283947 TI - [Prevalence of anti-HCV in the personnel of diverse health centers]. PMID- 1283948 TI - [Immunologic prevention of tetanus in the emergency service: preliminary investigation in 2 hospitals in Lazio and Abruzzo]. PMID- 1283949 TI - [Environmental diffusion of Legionella and of cases of legionellosis]. PMID- 1283950 TI - [Indoor air quality in a university didactic center: interdepartmental complex "A. Vallisneri". Evaluation of the conditions and the methodological experiences]. PMID- 1283951 TI - A new approach to the study of ovarian follicles by scanning electron microscopy and ODO maceration. AB - The ultrastructure of the follicle-oocyte complex in rodents and humans was revealed by high resolution scanning electron microscopy (SEM) following the Osmium-DMSO-Osmium maceration method (TANAKA and NAGURO, 1981). In primary follicles, the majority of oocyte organelles such as mitochondria and Golgi complex components are concentrated in a juxtanuclear area. In particular, many spherical mitochondria are oriented all around the nucleus. After maceration of the ooplasm matrix, most of these mitochondria appear intermingled with numerous microtubules (MT) and associated with many Golgi vesicles. Such a nuclear polarization of organelles, essential to the oocyte metabolism, might depend upon a MT activity. MT might guide mitochondria to gather in the perinuclear region and further maintain their close associated to the nuclear envelope. A similar relationship among microtubules, vesicular Golgi complex and mitochondria has been also observed when, in maturing oocytes, these organelles migrate and gather in other areas of the ooplasm. A pattern common only to human developing follicles appears in the occurrence of long microvilli projected from follicle cells deep into the oocyte. These unusual microvilli running within the ooplasm are surrounded by several vesicles of the Golgi complex and endoplasmic reticulum, and often end close to the nucleus. In the antral follicle, the microvilli of corona cells, directed toward the oocyte (after their full exposure through the chemical dissolution of the zona pellucida matrix) are extremely numerous (up to 70/cell), long (up to 7/10 microns) and tortuous. They resemble epididymal stereocilia, may be ramified and possess bulbous tips. In contrast, oocyte microvilli are thin and short.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283952 TI - Cellular and microvascular changes of the ovarian follicle during folliculogenesis: a scanning electron microscopic study. AB - In order to study the three-dimensional topographic arrangement of the oocyte and zona pellucida, follicular cells and follicle microvasculature, this study applied alkali maceration methods for tissue exposure, the ruthenium red detergent method for the extracellular matrix visualization, and the vascular corrosion cast technique to rabbits, guinea-pigs and mice ovaries at different stages of follicular development. Macerated samples showed a gradual differentiation of the oocyte surface. This, in primordial follicles, appeared rather smooth, but, with the follicular development, displayed a gradual increase of blebs and microvilli. The latter widely covered the surface of oocytes contained in large or mature follicles. The outer surface of the zona pellucida showed numerous fenestrations, whereas the inner one was smooth. The ruthenium red-detergent method permitted a well detailed view of the filamentous texture of the zona pellucida. The three-dimensional distribution of the contacts between oocyte and neighbouring follicular cells was clearly evaluated in macerated samples. Follicular cells of primary follicles were characterized by their short cytoplasmic processes reaching the oocyte surface. In secondary follicles, these processes issued secondary processes. In larger follicles, the secondary processes of the corona cells were much longer and thinner, and took a tortuous course to reach the oocyte surface, which ran among the numerous oocyte microvilli. This microvillous arrangement greatly increases contact between the oocyte and corona cells, and suggests a coordinated reciprocal control of the activities of both cell types. These data also showed that the spongy and filamentous nature of the zona pellucida is closely dependent upon the temporal differentiation and enormous increase in number of follicular cell projections and their ramifications. Maceration revealed the theca cells surface. In smaller follicles these appeared as fusiform cells which resembled fibroblasts. In larger or mature follicles, many theca cells differentiated to possess morphological features of steroidogenic cells. In addition, these cells delimited a series of intercellular communicating lacunae, continuous with wide pericapillary spaces. The gradual differentiation of the follicle towards a structure having an endocrinal role was further emphasized in vascular corrosion casts. A simple microvascular net made of thin capillaries supplying primary follicles was seen to transform into an elaborate sinusoidal network made of thick permeable capillaries, supplying mature follicles. PMID- 1283953 TI - Mouse/human chimeric anti-HIV-1 gp120 antibody to the principal neutralizing determinant: tolerability and pharmacokinetics in cynomolgus monkeys, Macaca fascicularis. AB - In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47,439 in HIV-1 infected individuals, it was administered to Macaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47,439/kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T1/2 alpha of 14.2 h (range 11.8-19.3 h) and a mean T1/2 beta of 172.6 h (range 137.2-220.5h). Following four successive antibody infusions serum concentrations of CGP 47,439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients. PMID- 1283954 TI - Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis. AB - Collagen induced arthritis is an experimental animal model of inflammatory polyarthropathy that has many features of human rheumatoid arthritis. Type II collagen is the major matrix protein of hyaline cartilage and is a sequestered protein which can be presented as an autoantigen under certain conditions. To induce CIA, type II collagen is injected intradermally with complete Freund's adjuvant. Susceptibility to CIA is dependent on the presence of the trimolecular complex: 1) the arthritogenic epitope on the type II collagen; 2) a class II MHC molecule on the accessory cell presenting the arthritogenic epitope; and 3) T cells expressing specific V beta chains in their TCRs. Complement and other non MHC background genes also may play a role in susceptibility to CIA. Both cell mediated and humoral immunity are involved in the pathogenesis of CIA. To date immunotherapies that have modulated CIA include use of anti-class Ii antibodies, anti-lymphokines, and monoclonal antibodies directed against specific cellular markers. All of these therapies are able to modulate disease to some extent but lack the specificity and efficacy to make them practical for widespread use in human disease. Most promising, is the use of monoclonal antibodies directed against specific V beta TCR subsets. This is potentially a very specific and effective therapy because it will affect only the cells involved in disease while leaving the host otherwise immunocompetent. Therapies on the horizon include the use of synthetic peptides with sequences homologous to various regions on the TCR, immunotoxins, and superantigens to modulate the immune response and ameliorate disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283955 TI - ConA induced changes in energy metabolism of rat thymocytes. AB - The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K(+)-ATPase, Ca(2+)-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K(+)-ATPase with about 20% each of total oxygen consumption, while Ca(2+)-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In contrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation. PMID- 1283956 TI - [Beta-adrenoblockers in the reorganizing of the food center of the hypothalamus under the influence of substance P]. AB - An ability of substance P (15 nmol intracerebroventricularly) to transform functional properties of the hypothalamic feeding center manifested in escape reaction in response to threshold electrical stimulation of this motivation center in rabbits. Beta-adrenergic antagonists inderal and obsidan (0.25, 0.5 mg, respectively) injected intravenously were found to restore feeding elicited by electrostimulation of the hypothalamic feeding center. However, escape reaction, elicited from the feeding center under substance P was found unchanged after intravenous administration of 0.25 mg kalipsol. The data obtained suggested an important role of beta-adrenergic mechanisms in substance P transformation of the functional properties of the hypothalamic feeding centre. PMID- 1283957 TI - [The effect of pentagastrin and substance P on the gastric parietal glandulocytes]. AB - Investigations on dogs show that substance P suppresses pentagastrin gastric acid secretion. This effect is abolished by acetylcholinesterase block by calimin. The results indicate that pentagastrin and substance P participate in cholinergic regulation of gastric acid secretion. PMID- 1283958 TI - [The dynamics of the extinction of brain cellular biosynthesis at different times after death]. AB - The paper presents experimental data on RNA synthesis in neuronal, glial, endothelial cells of a dying organism. Under certain conditions it is possible to define labelled cells in the majority of the brain cells within post-death hours 1-4. This fact proves that genome is still functioning. Endothelial cells possess higher vital capacity. CNS neurons are capable of synthesizing RNA within the period of up to 4 hours after death of the organism. PMID- 1283959 TI - Low incidence of pulmonary Pseudomonas cepacia infection in Danish cystic fibrosis patients. PMID- 1283960 TI - The school nurse's role: early intervention with preschool children. AB - With the advent of PL99-457, preschoolers are increasingly appearing in the educational system. The school nurse must have an understanding of the basis for early entrance of these children and methods by which they obtain entry. This article focuses on the diagnosis of developmental delay in preschool children and identifies some of the specific roles and functions involving the school nurse. PMID- 1283961 TI - Heterogenous distribution of peptide-containing nerve fibres within the circular muscle layer of the human pylorus. AB - The distribution of nerve fibres immunoreactive for vasoactive intestinal polypeptide (VIP), substance P (SP), methionine-enkephalin (ENK), calcitonin gene related peptide (CGRP) and neuropeptide Y (NPY) within the circular muscle layer was examined histochemically in the human pylorus, adjacent antrum and duodenum. Longitudinal cryostat sections of the pyloric and surrounding regions were stained by an indirect immunofluorescence method, and the total length of each type of peptide-containing fibre per unit sectional area (micron/mm2) was measured using an image-analysing system. The narrow region of the circular muscle layer bordering the submucosa in the pylorus contained a rich supply of VIP, SP, ENK and CGRP immunoreactive fibres; VIP fibres were most prominent with less SP and ENK fibres and moderate amounts of CGRP. These peptide-containing nerve fibres were more dense than in the pyloric circular muscle, the longitudinal muscle layer and also the adjacent muscle layer. NPY-immunoreactive fibres were sparsely distributed throughout the pyloric region. These results suggest that the inner edge of the circular muscle, lying adjacent to the submucosa and densely innervated with peptide-containing fibres, may be a characteristic feature of the human pyloric sphincter. PMID- 1283962 TI - Protein hydration in aqueous solution. AB - Proton nuclear magnetic resonance was used to study individual molecules of hydration water bound to the protein basic pancreatic trypsin inhibitor (BPTI) and to the nonapeptide oxytocin in aqueous solution. The experimental observations are nuclear Overhauser effects (NOE) between protons of individual amino acid residues of the protein and those of hydration water. These NOEs were recorded by two-dimensional (2D) and three dimensional (3D) NOE spectroscopy (NOESY) in the laboratory frame, and by the corresponding experiments in the rotating frame (ROESY). The studies show that there are two qualitatively different types of hydration sites. Four water molecules in the interior of the BPTI molecule are in identical locations in the crystal structure and in solution. Their NOEs with the protein protons are characterized by large negative cross-relaxation rates sigma NOE, which indicates that the residence times of the water molecules in these hydration sites are longer than ca. 10 ns. Additional experiments with extrinsic shift reagents established an upper limit of 20 ms at 4 degrees C for these residence times. Surface hydration of both the globular protein BPTI and the flexibly disordered polypeptide oxytocin is by water molecules with residence times in the subnanosecond range, as evidenced by small positive sigma NOE values observed for their NOEs with nearby polypeptide protons. Short residence times prevail for all surface hydration sites, independent of whether or not they are occupied by well ordered, X-ray observable water in the protein single crystals. PMID- 1283963 TI - Ion channels in the regulation of growth hormone secretion from somatotrophs by somatostatin. PMID- 1283964 TI - Activated protein kinase C directly phosphorylates the CD34 antigen in acute lymphoblastic leukemia cells. AB - The precursors of all blood cell lineages are contained within the 1-3% of bone marrow cells which express the CD34 antigen, and this population can reconstitute the hematopoietic system of lethally irradiated animals and humans. A potential regulatory role for the CD34 antigen in progenitor cell function and differentiation was indicated by our recent findings that the CD34 antigen can be phosphorylated in vivo to high stoichiometry in primitive CD34+ cell-lines by activated protein kinase C. To exclude the possibility that these effects were restricted to cell-lines, we have performed similar experiments on fresh cells from a patient with drug-resistant acute lymphoblastic leukemia. Similar to our previous findings, we found the CD34 antigen to be hyperphosphorylated in lymphoblasts labeled in the presence of active phorbols. The same peptides which were hyperphosphorylated in phorbol-stimulated cell-lines were also phosphorylated in phorbol-stimulated lymphoblasts. These data indicate that CD34 is a substrate molecule for PKC in fresh CD34+ lymphoblasts and underline the role of modulators of PKC activity in the biology of primitive leucocytes. PMID- 1283965 TI - Autoantibody activity and V gene usage by B-cell malignancies. AB - Autoreactive B cells account for a substantial part of the B-cell repertoire. They frequently secrete polyspecific natural autoantibodies, which probably bind with low affinity to the different antigens they recognize and which express germinal genes. The role of this pre-immune repertoire still remains to be defined but it has been suggested that it participates in the elimination of cell breakdown products, serves as a first barrier of defense or acts as a template upon which antigen driven selection and somatic recombinations could induce the emergence of high affinity induced antibodies. The present study, reviews the evidence favouring the idea that this autoreactive B-cell repertoire, which expresses a restricted set of V genes, frequently undergoes malignant transformation. This evidence arises from the study of the autoantibody activity and V gene usage in three different models of B-cell malignancies namely monoclonal immunoglobulins; chronic lymphocytic leukemia; and follicular non Hodgkin's lymphomas. PMID- 1283966 TI - Comparison of two methods for concentrating CD34+ cells from patients with acute non-lymphocytic leukemia. AB - The aim of the present study was to compare two different methods for obtaining CD34+ cells from the peripheral blood or the bone marrow of patients with acute non-lymphocytic leukemia (ANLL). Twenty-two samples, obtained from 19 patients, were density cut (Ficoll-Hypaque 1.077) and, after incubation with My10 antibody, separated by panning or by immunomagnetic beads. Immunomagnetic beads provided a significantly better separation than panning, either in terms of concentration of CD34+ cells (85.5 +/- 11.6% vs. 55.7 +/- 25.0%, p = 0.003) or in terms of depletion of CD34+ cells (3.9 +/- 8.0% vs. 30.9 +/- 26.3%, p = 0.008). This was consistent with the virtually complete depletion of colony forming cells (CFC) in the CD34 negative fraction and the recovery of virtually all the CFC in the positive fraction in the samples separated by immunomagnetic beads. In conclusion, separation by immunomagnetic beads can allow collection of nearly pure CD34+ and CD34- cell populations from patients with ANLL, thereby facilitating the study of the biological characteristics of these cell populations. Moreover the method is less time consuming than panning and is not toxic to the CFC. PMID- 1283967 TI - [Alpha fetoprotein levels in the serum and bronchoalveolar lavage fluid in patients with lung cancer and other diseases of the respiratory system]. AB - Concentration of alpha-fetoprotein (AFP) may be increased in some type of lung cancer. In the study concentration of AFP was evaluated in serum and broncho alveolar lavage fluid (BALF) in patients with lung cancer. The values of concentration were compared with results obtained from patients with other diseases of the respiratory tract. Examinations were performed in 14 patients with lung cancer, 12 with sarcoidosis, 23 with chronic obstructive bronchitis and 16 with acute bronchitis. Liver pathology was excluded according to biochemical analytical tests. In all patients bronchofibroscopy was performed and BALF was obtained in routine way. Concentration of AFP in serum and BALF was determined by immuno-assay technique. In performed examinations non significant increase of AFP concentration was determined in serum and BALF of patients with lung cancer. However, obtained values were increased twice than in patients with acute bronchitis. Moreover, it was noticed that in patients with chronic obstructive bronchitis the AFP concentration was the highest, especially in the group treated by steroids. The study indicates that evaluation of AFP concentration is out of value in diagnosis and differentiation of lung cancer. It seems to be necessary to continue the examinations for explanation a role of steroids in inflammatory process and increase of AFP concentration. PMID- 1283968 TI - [Reactivity of pulmonary mast cells and peripheral blood basophils in patients with sarcoidosis and bronchial asthma]. AB - We have studied the sensitivity of pulmonary mast cells and blood basophils in patients with sarcoidosis and bronchial asthma. The cells were induced in vitro with anti-IgE. The histamine releasing from mast cells and basophils was high in both examined groups of patients. The histamine releasing from mast cells in patients with sarcoidosis was 27.8-47.1% and in asthmatic patients 42.8-58.9%. The histamine releasing from basophils was 38.2-57.9% and 41.0-62.1%, respectively. The high sensitivity of mast cells of patients with sarcoidosis may suggest that these cells play an essential role in pathology of this disease. PMID- 1283969 TI - Comparison of the vasoconstrictor responses induced by endothelin and phorbol 12,13-dibutyrate in bovine cerebral arteries. AB - The vascular effects of endothelin-1 (ET-1) were compared with those elicited by phorbol 12,13-dibutyrate (PDB), an activator of the protein kinase C (PKC), to analyze the involvement of this enzyme on ET-1 responses. PDB and ET-1 caused slow-developing contractions (sustained and transient, respectively), which were reduced by the PKC inhibitor, staurosporine (1 and 10 nM). Only the contractile effects evoked by ET-1 were reduced in Ca-free medium and by the Ca channel antagonist, nifedipine (1 microM), and increased by the Ca channel agonist, BAY K 8644 (10 nM). PDB (10 and 30 nM) preincubation reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT; 0.01, 0.1 and 1 microM) in a way dependent on phorbol concentration and preincubation time, whereas ET-1 (1 nM) increased the contractile response to 5-HT (0.1 microM). Furthermore, PDB (0.1 microM) also reduced the responses elicited by ET-1 (30 microM) and vice versa. ET-1 (0.1 microM) induced transient translocation of PKC activity from the cytosol to the membrane, which was less than that produced by PDB (0.1 microM). Electrical stimulation induced [3H]noradrenaline (NA) release, which was increased by PDB (10 and 100 nM) and not affected by ET-1 (10 nM). These results indicate: (1) the responses induced by PDB and ET-1 were independent and dependent on extracellular Ca, respectively; (2) PKC is involved in NA release and 5-HT responses, but mainly in desensitization of these responses, and (3) PKC is activated by ET-1 and is implicated in vascular actions of ET-1, but other mechanisms, such as the activation of ET-1 receptors and opening of dihydropyridine-sensitive Ca channels also appear to be involved. PMID- 1283970 TI - CRF-like immunoreactivity selectively labels preganglionic sudomotor neurons in cat. AB - Immunohistochemical and neuronal tracing methods were used in cats to determine which type of postganglionic sympathetic neuron is innervated by preganglionic neurons which contain corticotrophin releasing factor-like immunoreactivity (CRF LI). Preganglionic neurons with CRF-LI have their cell bodies at two restricted levels of the spinal cord and terminate in the stellate and lower lumbar ganglia. CRF-LI terminal baskets in stellate and lumbar ganglia surrounded cell bodies, 96 99% of which showed no tyrosine hydroxylase (TH)-LI (presumptive cholinergic neurons). Calcitonin gene-related peptide (CGRP)-LI was used to label the cholinergic ganglion cells which innervate sweat glands: 96-99% of those were confirmed as lacking TH-LI, while the remainder showed weak staining. Every one of over 6000 CRF-LI terminal baskets counted in 4 stellate and 6 lumbar ganglia was found to surround a cell body with CGRP-LI; conversely, 81-86% of the cell bodies showing CGRP-LI were surrounded by CRF-LI terminal baskets. In 3 cats, the retrograde tracer fluorogold was used to label postganglionic neurons projecting to the paw pads (a population which includes both cholinergic sudomotor neurons and noradrenergic vasoconstrictor neurons). Between 26 and 38% of the retrogradely labelled ganglion cells were surrounded by CRF-LI terminal baskets. We conclude that in cats, preganglionic sympathetic neurons with CRF-LI are sudomotor in function. PMID- 1283971 TI - Effect of substance P on respiratory rhythm and pre-inspiratory neurons in the ventrolateral structure of rostral medulla oblongata: an in vitro study. AB - The pre-inspiratory (Pre-I) neurons which fire in the pre- and usually also during the post-inspiratory phase are located in the ventrolateral structures of the rostral medulla. They are suggested as primary rhythm generating neurons for respiration. These have been studied in isolated brainstem-spinal cord preparations from newborn 0-5-day-old rats. We have found that application of substance P (SP) enhanced the respiratory rhythm as measured by C4 ventral root and pre-I neuronal activities. Furthermore, the effect of SP was dependent on basal respiratory rate. An increase of the Pre-I and C4 burst rate by SP was clearer when the basal respiratory rhythm was somewhat lower. Moreover, long lasting depression of respiratory rate after the application of the alpha 2 agonist clonidine was reversed by SP. On the other hand, an inhibitory effect appeared in preparations with a higher basal respiratory rate, while the Pre-I burst rate tended to increase during SP perfusion. During chemical synaptic transmission blockade by perfusion with low Ca2+, high Mg2+ solution, a pre-I burst retained or completely blocked was found to be enhanced or reactivated by SP perfusion. The results suggest a direct postsynaptic action of SP, which could strongly stimulate burst generating properties of Pre-I neurons. PMID- 1283972 TI - Morphine induces an increase in extracellular serotonin in the rat diencephalon. AB - The effect of systemic morphine on extracellular serotonin (5-HT) in the diencephalon of unanesthetized, unrestrained rats was investigated by in vivo microdialysis coupled to high performance liquid chromatography with electrochemical detection. Administration of morphine resulted in a dose dependent increase in extracellular 5-HT. Significant increases were first seen at a dose of 5 mg/kg, and a maximal increase occurred at 10 mg/kg. This increase was blocked by pretreatment with naltrexone, indicating that the effect of morphine on 5-HT was mediated by opiate receptors. Morphine also had a significant effect on extracellular 5-hydroxyindoleacetic acid (5-HIAA), leading to a gradual increase across a range of doses. The effect of morphine on 5-HT was compared to effects of morphine on nociception and catalepsy. Increases in 5-HT and 5-HIAA were first detected at doses that were analgesic but too low to elicit catalepsy. Consistent with many reports that opioids cause an increase in synthesis and turnover of 5-HT in the rat forebrain, the present results provide more direct evidence that 5-HT release is increased after morphine administration. PMID- 1283973 TI - [A preliminary approach to pathological and biochemical changes of the lungs injured by domestic pingyangmycinum]. AB - Two hundred male mice, weighing 18-24g, were randomized into four groups. A model of lung injury was established in mice by intratracheal administration of a single dose of domestic pingyangmycinum (Bleomycin A5). The dose-effect relationship for different doses of pingyangmycinum (0.05, 0.1, 0.2 mg) on the lung injury, and the change of hydroxyprolin (Hyp), ceruloplasmin (CP), angiotensin converting enzyme (ACE), superoxide dismutase (SOD) in mice were investigated. The results showed that the pathological changes of alveolitis and pulmonary interstitial fibrosis were more severe, and mortality of the mice was increased when pingyangmycinum dose was increased. During 2-6 weeks of this experiment, Hyp, CP, ACE and SOD in serum and Hyp in lung tissue were increased in different degrees. However, the activity of SOD in lung tissue was decreased. The possible mechanism of this lung injury is also discussed. PMID- 1283974 TI - [Coexpression of intermediate filaments in notochords and chordomas and its significance in the histogenesis and diagnosis of chordoma]. AB - Six chordomas, ten fetal notochords and eight adult notochords were stained for keratin, vimentin, GFAP, desmin, CEA, EMA and s-100 protein. Coexpression of four kinds of intermediate filaments was common in fetal notochords and chordomas. According to the histologic and immunohistochemical characteristics, chordoma may originate from the ectopic remnants of undegenerated notochord during the embryonic stage. The chordoma consists of two cell types; nonvacuolated and physaliphorous cells, and exhibits the potentiality of multidirectional differentiation. The coexpression of different types of intermediate filaments could explain the morphological transformation of chordoma. PMID- 1283975 TI - [The abnormal cytokeratin expression in HBV-caused hepatitis, early-cirrhotic and cirrhotic livers, its mechanism and significance]. AB - An ABC immunohistochemical study of the expression of cytokeratin (CK19 and CK18) was carried out in 315 cases of HBV-caused hepatitis, early-cirrhotic and cirrhotic livers. It was shown that hepatocytes in 73% of chronic active hepatitis (CAH) (80/110) and 81% of early-cirrhotic and cirrhotic livers (117/144) expressed CK19 (the abnormal CK expression), which could be of help in differentiating CAH from chronic persistent hepatitis, subtype CAH (mild, moderate to severe type) and in determining the activity of early-cirrhotic and cirrhotic livers. The abnormal CK expression was shown to be closely related to the activity of liver disorders. The CK19 expression in hepatocytes had the closest relations with the piece-meal necrosis of hepatocytes, isolation of hepatocytes into groups by connective tissue, and fibrosis. It is suggested that CK19 expression may be one of the local reactions to the piece-meal necrosis of hepatocytes. PMID- 1283976 TI - [Clinical and pathological features of primary hepatocellular carcinoma in 26 patients survived over 10 years after operation]. AB - The clinical and pathological features of primary hepatocellular carcinoma (PHC) in 26 patients who had survived over 10 years after operation were analyzed. The results were as follows: 84.62% (22 patients) were detected by AFP screening, 80.77% (21 patients) were in clinical stage I, 76.96% (20 patients) were younger than 45 years of age. Serum AFP of all patients turned negative within 2 months after operation. The tumor diameters ranged from 1.2 cm to 15 cm, and solitary tumors accounted for 80.77% (21 patients). All tumors were encapsulated and infiltrated by lymphocytes. Cirrhosis was found only in 9 cases (34.62%). The positive rates of HBsAg and HBcAg were 80% and 15% respectively in hepatic tissues surrounding the carcinoma. These results suggest that good prognosis or long survival is related to early detection, younger age of the patient, solitary tumor, better encapsulation, mild injury of the surrounding liver tissues, and rapid negative turning of AFP after operation. PMID- 1283978 TI - JSB versus giemsa stain: an evaluation. PMID- 1283977 TI - Influence of low doses of BrdU and estimation of spontaneous SCE in CHO chromosomes: three-way differential staining and an immunoperoxidase method. AB - The influence of low doses of 5-bromodeoxyuridine (BrdU) on the occurrence of sister chromatid exchanges (SCEs) during the first cell cycle, when unsubstituted DNA templates replicate in the presence of the halogenated nucleoside (SCE1) has been assessed in third mitosis (M3) Chinese hamster ovary (CHO) cells showing three-way differential (TWD) staining. In addition, lower concentrations of BrdU, not detectable by Giemsa staining, have been tested by a high resolution immunoperoxidase method (anti-BrdU monoclonal antibody) and SCEs were scored in second mitosis (M2) cells. Our findings was a dose-response curve for SCE1 that allows an estimated mean spontaneous yield of 1.32/cell per cell cycle by extrapolation to zero concentration of BrdU. On the other hand, when the total SCE frequency corresponding to the first and second rounds of replication (SCE1 + SCE2) found in M3 chromosomes was compared with the yield of SCEs scored in M2 cells grown in BrdU at doses lower than 1 microM no further reduction was achieved. This seems to indicate that SCEs can occur spontaneously in this cell line, though the estimated frequency is higher than that reported in vivo. PMID- 1283979 TI - Effects of calmodulin inhibitors on amylase secretion from rat pancreatic acini. AB - To investigate the role of calmodulin in stimulus-secretion coupling in pancreatic acinar cells, we studied the effects of W-7, a calmodulin inhibitor, and KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CaM kinase II), on amylase secretion from rat pancreatic acini. Calmodulin inhibitor (W-7, 100 microM) and Ca2+/CaM kinase II inhibitor (KN-62, 10 microM) reduced amylase secretion stimulated by cholecystokinin (CCK) or carbachol. W-7 and KN-62 also inhibited amylase secretion stimulated by both calcium ionophore (A23187) and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA). To clarify the role of calmodulin in the interaction of intracellular mediators, pancreatic acini were permeabilized with streptolysin O. Following permeabilization, amylase secretion was stimulated by submicromolar free Ca2+, and this Ca(2+)-dependent amylase secretion was enhanced by guanosine 5'-[gamma thio]triphosphate (GTP gamma S), TPA or cyclic adenosine 3',5'-monophosphate (cAMP). W-7 and KN-62 had no effects on amylase secretion stimulated by Ca2+ alone, but inhibited the enhancement in Ca(2+)-dependent amylase secretion by GTP gamma S, TPA or cAMP. These data suggest that calmodulin plays an important role in Ca(2+)-dependent amylase secretion from pancreatic acinar cells and in the interaction between Ca2+ and other intracellular messengers. PMID- 1283980 TI - Sero-surveillance of transmissible hepatitis B & C viruses in asymptomatic HIV infection in haemophilics. AB - In a group of 37 haemophilics, 9 (24.3%) were seropositive for human immunodeficiency virus (HIV), while 9 (24.3%) and 10 (27%) were positive for hepatitis B virus (HBV) and hepatitis C virus (HCV) respectively. Haemophilics who were HIV seropositive had higher prevalence of HBV and HCV. Seropositivity for HIV was more in patients with severe haemophilia A who required frequent factor VIII replacement. The need for long term surveillance of voluntary blood donors for transfusion associated viruses like HIV, HBV and HCV, is emphasized. PMID- 1283981 TI - Effects of growth hormone administration in addition to gonadotrophins in normally ovulating women and polycystic ovary syndrome (PCO) patients. AB - Follicular fluid sex-steroids, insulin-like growth factor-I (IGF-I), IGF-I binding protein (IGF-I-BP) and epidermal growth factor were investigated in patients with polycystic ovaries and normally ovulating women, following ovulation induction with gonadotrophins or growth hormone plus gonadotrophins. Growth hormone supplementation enhanced the ovarian response to gonadotrophins, and significantly increased follicular fluid IGF-I in both groups, without affecting follicular fluid epidermal growth factor; growth hormone supplementation significantly decreased follicular fluid androstenedione in both groups. PMID- 1283982 TI - The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP 1) in the pathogenesis of polycystic ovary syndrome. AB - The objective of this study was to elucidate the relationship and role of insulin like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), insulin and luteinizing hormone (LH) in the pathogenesis of polycystic ovary syndrome (PCOS). In a pilot study, serum concentrations of IGF-1 were determined in women with PCOS (n = 10), hypopituitarism (n = 12) and normal controls (n = 10). In the main study, serum concentrations of IGF-1, IGFBP-1, insulin and LH in women with anovulation associated (n = 23) and not associated (n = 47) with PCOS were determined. Serum concentrations of IGF-1 were not different in women with PCOS, anovulatory non-PCOS and healthy women but were low in those with hypopituitarism. Mean serum IGFBP-1 in PCOS (33.8 +/- 21.2 micrograms/l) was decreased compared with anovulatory non-PCOS (60.0 +/- 22 micrograms/l) (P = 0.0001), and correlated negatively with insulin concentrations (r = -0.67, P = 0.0006). Patients with PCOS could be separated into those with high LH and those with high insulin levels. It was concluded that women with PCOS have normal serum IGF-1 concentrations but IGFBP-1 levels, regulated by insulin, are low. Hyperinsulinaemia and raised LH are independently capable of stimulating ovarian androgen production. Growth factors may have an important role in the pathogenesis of PCOS. PMID- 1283983 TI - Recurrence of hyperthyroidism in multinodular goiter after long-term drug therapy: a comparison with Graves' disease. AB - The chance of permanent remission after prolonged drug therapy was investigated in 41 patients with toxic multinodular goiter. For purposes of comparison a group of 41 patients with Graves' disease was also studied. After euthyroidism was achieved all patients received a combination of thionamide and thyroxine for at least 12 months. The minimum follow-up period was 2 yr. Relapse of thyrotoxicosis occurred in 95.1% of patients with toxic multinodular goiter and 34.1% of patients with Graves' disease (p < 0.001). It is concluded that for patients with toxic multinodular goiter early radioiodine therapy or surgery is preferred since prolonged drug therapy seldom produces permanent remission. PMID- 1283984 TI - Antithyroid drug and Graves' hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission. AB - OBJECTIVE: To investigate the significance of treatment with antithyroid drugs longer than 12 months on lasting remission in Graves' hyperthyroid patients, and to study clinical and laboratory parameters of prognostic value. PATIENTS: Fifty two untreated Graves' hyperthyroid patients were assigned at random to two therapeutic groups. They were treated with carbimazole during 12 and 24 months in Group I (n = 28) and Group II (n = 24), respectively. MEASUREMENTS: Serum levels of FT4, T3, sTSH and TSH receptor antibody (TRAb) were measured before starting treatment and at regular intervals during treatment and follow-up after drug withdrawal. We compared the relapse rate in both groups of patients, at short (2 yr) and long-term (5-yr) periods after drug withdrawal. Also, we compared clinical and biochemical parameters between patients who stayed in remission and who had relapse. RESULTS: At the end of the short-term period, relapse had occurred in 13 (46.4%) Group I patients and in 13 (54.1%) Group II patients, p = 0.36. At the end of the long-term period, relapse had occurred in 24 (85.7%) Group I and 20 (83.3%) Group II patients, p = 0.78. No difference could be observed between patients who had stayed in remission and who had suffered relapse, within the 5-yr follow-up period regarding to goiter size, frequency of ophthalmopathy, TSH and TRAb levels. CONCLUSIONS: The high relapse rate observed could be due to high iodine intake in our country. In this study and in a review of the available data, we have been unable to find any rational basis for courses of antithyroid drugs longer than twelve months for the treatment of Graves' hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1283985 TI - A calcium conducting channel akin to a calcium pump. AB - Calcium conducting channels were studied in blebs of sarcoplasmic reticulum described by Stein & Palade (1988). The calcium channels had at least three conductance states (70 pS, 50 pS and 37 pS) and were weakly selective for calcium ions, with a permeability ratio Ca2+ to K+ of about 3.4. The open probability of the channel was strongly voltage dependent, decreasing at positive membrane voltages. 10 microM ryanodine and 5 microM ruthenium red had no effect on this channel; neither did millimolar concentrations of ATP, Mg2+, caffeine, and Ca2+, implying that the calcium conducting channels are not ryanodine receptors. Several calcium pump inhibitors--namely, vanadate, AlF4-, reactive red 120, and cyclopiazonic acid--had obvious effects on the calcium conducting channels, suggesting that the calcium conducting channel of SR membrane blebs is some form of the SR calcium pump. PMID- 1283987 TI - Ophthalmology and mythology. PMID- 1283986 TI - Calcium-independent K(+)-selective channel from chromaffin granule membranes. AB - Intact adrenal chromaffin granules and purified granule membrane ghosts were allowed to fuse with acidic phospholipid planar bilayer membranes in the presence of Ca2+ (1 mM). From both preparations, we were able to detect a large conductance potassium channel (ca. 160 pS in symmetrical 400 mM K+), which was highly selective for K+ over Na+ (PK/PNa = 11) as estimated from the reversal potential of the channel current. Channel activity was unaffected by charybdotoxin, a blocker of the [Ca2+]-activated K+ channel of large conductance. Furthermore, this channel proved quite different from the previously described channels from other types of secretory vesicle preparations, not only in its selectivity and conductance, but also in its insensitivity to both calcium and potential across the bilayer. We conclude that the chromaffin granule membrane contains a K(+)-selective channel with large conductance. We suggest that the role of this channel may include ion movement during granule assembly or recycling, and do not rule out events leading to exocytosis. PMID- 1283988 TI - [Regulation of vascular tone by nitric oxide (NO) derived from endothelium and nerve]. PMID- 1283989 TI - [The role of endothelial function in the pathogenesis of coronary spasm in humans]. PMID- 1283990 TI - [Metabolic regulation of the cardiac gap junctional current flow- electrophysiological and magnetic resonance studies]. PMID- 1283991 TI - Immunohistochemical study of the histogenesis of esophageal carcinosarcoma. AB - In order to clarify the histogenesis and the direction of differentiation of spindle-cell and sarcomatous components of esophageal carcinosarcoma, 20 cases of the disease were reviewed histologically and immunohistochemically using the avidin-biotin-peroxidase complex method with monoclonal and polyclonal antibodies to various keratins, vimentin, desmin, muscle specific actin and S-100 protein. A gradual transition between carcinomatous and spindle cell sarcomatous components was present histologically in all 20 cases. Positive immunoreactivity for keratins was found in carcinomatous areas in all cases. Spindle cells in the transitional areas were positive for keratins in nine cases and for vimentin in five. Two cases demonstrated trace positive reactions to both keratin and vimentin in the same areas of transitional spindle cells between carcinomatous and sarcomatous components. The sarcomatous component showed an immunohistochemically positive reaction for vimentin in ten cases and for desmin in two. In one of the 20 cases, chondrosarcomatous cells were seen which showed a positive reaction to S-100 protein but were negative to keratin. The findings strongly suggested that neoplastic epithelial cells may show dedifferentiation to transforming spindle cells and also disdifferentiation to non-epithelial sarcoma like chondrosarcoma and leiomyosarcoma. PMID- 1283992 TI - Immunohistochemical detection of Pneumocystis carinii in transbronchial lung biopsy specimens: antigen difference between human and rat Pneumocystis carinii. AB - Transbronchial lung biopsy specimens, from three patients with non-AIDS-related Pneumocystis carinii pneumonia (PCP) and rat lung tissue in which PCP was induced by the administration of dexamethasone, were studied to determine the diagnostic usefulness of an immunohistochemical method using commercially available anti Pneumocystis monoclonal antibody, 3F6, on formalin-fixed, paraffin-embedded tissue. PC was consistently stained a bright red color and unambiguously identified in all three human lung specimens, but not stained in lung tissues at autopsy from patients with various fungal pneumonias. In contrast, PC was weakly stained in PCP-induced rat lungs. The present study indicates human PC and rat PC to be antigenically different in terms of the existence of the 82 kilo-dalton (kD) antigen against which 3F6 is directed. PMID- 1283993 TI - Comparison of various assay systems for prostate-specific antigen standardization. AB - To avoid confusion between serum prostate-specific antigen (PSA) values among various assay systems, clinical studies on the possibility of conversion among detection values were performed. The assay kits used for the PSA comparisons were MARKIT-F PA, MARKIT-M PA, EIKEN PA, PA test WAKO, Ball ELSA PSA, E-Test Tosoh II PA, PROS-CHECK PSA, DELFIA PSA and TANDEM-R PSA. Using each kit, the standards attached to each assay system were detected, and 142 sera samples from benign hypertrophies or prostate cancers were assayed for serum PSA values. By detecting the standards for each kit, slopes were obtained which were almost identical to those obtained from original assay system. The coefficients of correlation among the PSA detection systems, using patients' sera, were very high, and linear regression lines were also obtained. The results suggest that almost identical serum PSA values may be detected either by multiplying by a coefficient to bring it to the standard or using the conversion formula. PMID- 1283994 TI - Malignant sex-cord stromal tumor of the testis: report of a case with special reference to its unusual intracytoplasmic substructures. AB - A case of malignant sex-cord stromal tumor (gonadal stromal tumor) in the left testis of a 42-year-old man with no sign of hormonal abnormality is reported. Histologically, a large portion of the tumor was composed of solid nests of round cells with a moderate amount of eosinophilic cytoplasm, but some areas contained small spaces somewhat resembling Call-Exner bodies and/or the follicular structures of granulosa cell tumors. In general, however, the tumor cells did not show a clear-cut differentiation into either Sertoli cells or granulosa cells. The tumor, because of its high mitotic rate, lymphatic, venous and capsular invasion, and metastasis to the para-aortic lymph nodes, was considered to be malignant. We simply designated this tumor, therefore, as a malignant sex-cord stromal tumor. An ultrastructural study revealed unique intracytoplasmic bodies composed of multiple stacks of tubular structures which superficially mimicked annulate lamellae. No lipid droplets, Reinke's crystalloids or Charcot-Bottcher filaments were seen. The rarity of the tumor and the presence of unusual substructures prompted us to report the case. PMID- 1283995 TI - T-cell hybridomas recognizing the envelope proteins of Semliki forest virus: their sensitivity to endo/lysosomal protease and the antigenicity. AB - Eight T-cell hybridomas were established from the draining lymph node of C3H mice immunized with Semliki forest virus (SFV). Six of them showed specificity toward viral-structure protein E2, while the remaining two clones included one with specificity to an other structural protein E1 and the other with specificity to C. The production of IL-2 by the E2 protein-specific T-cell hybridomas in the presence of SFV was suppressed by treating the antigen-presenting cells (APC) with ammonium chloride raising pH of the acidic compartments. It was found also that treatment of APC with a thiol protease inhibitor, leupeptin or E64, resulted in a reduced response of some of the E2-specific T-cell hybridomas. The E2 protein of SFV proved to be resistant at pH 7.0, and sensitive at pH 5.0 to in vitro cathepsin B treatment. In contrast, the E1 and C proteins proved to be resistant to both pH values. These results indicate that the thiol protease, probably cathepsin B, works as one of the enzymes group involved in antigen processing. PMID- 1283996 TI - [A new approach to the intraoperative diagnosis of cholangitis and to the choice of surgical procedure in operations on the bile ducts]. AB - The authors have developed a prompt and informative method for assessment of the depth and reversibility of the morphofunctional changes in the common bile duct (CBD) wall with the use of staining by hematoxylin basic, fuchsin-picric acid. Four types of the morphologic changes in CBD wall, which characterize the different degree of reversibility, were established. Depending of presence of these types, the corresponding surgical tactics is recommended. PMID- 1283997 TI - Effects of sodium butyrate on the expression of sodium channels by neuronal cell lines derived from the rat CNS. AB - We have studied the effects of sodium butyrate on cell morphology and the expression of mRNAs encoding voltage-gated sodium channels in five neuronal cell lines, B35, B50, B65, B103 and B104, all derived from the rat CNS. The cells were grown in medium supplemented with 2.5 mM sodium-n-butyrate and examined daily by phase-contrast microscopy. Sodium butyrate caused slowing of cell division and the formation of longer and more highly branched cytoplasmic processes than were present in untreated cells. Expression of sodium channel mRNA was analysed by PCR with primers that allow the transcripts encoding the different types of sodium channel to be distinguished according to the lengths of the PCR products. The identity of the PCR products was confirmed by restriction enzyme digestion. Southern blotting and hybridization with internal radiolabelled probes. Prior to sodium butyrate treatment, expression of sodium channel mRNA was largely restricted to B50 and B104 cells: B50 cells showed expression of rat brain types I and II sodium channel and B104 cells expressed rat brain type III sodium channel. After treatment for 5 days with sodium butyrate, sodium channel mRNA was detected in all five cell lines. In addition to type I and type II sodium channel, B50 cells expressed rat brain type III sodium channel. These three types of sodium channel were also expressed by B35, B65 and B103 cells. Even after butyrate treatment, B104 cells expressed only type III sodium channel. The treatment also induced expression of rat skeletal muscle SkM1 sodium channel in B35 cells but only trace amounts in the other neuronal cell lines. PMID- 1283998 TI - The lipooligosaccharide immunotype as a virulence determinant in Neisseria meningitidis. AB - We have studied the antigenic (immunotype) and physical characteristics of the lipooligosaccharide (LOS) of epidemiologically related Neisseria meningitidis case (36) and carrier (76) isolates associated with a virulent clone of meningococci (ET-5 complex). LOS immunotypes were determined by dot blotting using immunotype specific monoclonal antibodies and physical characteristics were determined from silver stained SDS-PAGE following proteinase K digestion. The genetic similarity of the different isolates was confirmed by analysis of the restriction fragment length polymorphisms. An association between LOS immunotype expression and invasive disease was found; 97% of case isolates expressed the L3,7,9 immunotype, of which 13% additionally expressed the L1,8,10 determinant. The LOS immunotypes of carrier strains were much more heterogeneous. The predominant immunotype was L1,8,10 (70%) and only 24% expressed L3,7,9 alone. Genotypically related case isolates from Norway (6) and Austria (18) expressed the L3,7,9 immunotype with similar frequency to the U.K. isolates. The combination of LOS immunotype and capsule expression appears to be related to the virulence of these meningococcal strains. PMID- 1283999 TI - Conserved regulatory mechanisms of tyrosinase genes in mice and humans. AB - In vertebrates, melanin production is restricted to pigment cells. This cell type specific melanogenesis is considered to involve cell type-specific expression of the tyrosinase gene. Recently, there have been several reports that sequences in the 5' flanking region of the mouse tyrosinase gene are responsible for cell type specific expression of the transgene in mice. As the first step in the study of the evolution of the regulatory mechanisms for tyrosinase gene function in vertebrates, we constructed a fused gene, hg-Tyrs-J, which includes a 1.0-kb 5' flanking sequence of the human tyrosinase gene fused with mouse tyrosinase cDNA. By introducing the fused gene into fertilized eggs of albino mice, we obtained two mice that exhibited pigmentation in the skin and eyes and established a transgenic line from one of them. Further analyses revealed that the transgene was expressed cell type-specifically in these transgenic mice. We conclude, therefore, that the 1.0 kb 5' upstream region of the human tyrosinase gene contains conserved cis-elements essential for cell type-specific expression of the tyrosinase genes in mice and humans. Results of our study may provide a clue to elucidate the evolutionary process of regulatory mechanisms of the tyrosinase gene. PMID- 1284000 TI - Cleft lips and palates: a multidisciplinary approach. AB - Families of infants born with congenital defects such as cleft lip, cleft palate, and combinations of these often grasp with accepting the condition. Nurses can help facilitate acceptance by parents and families and play a key role in the management and habilitation of these children. PMID- 1284001 TI - Extinguishing burn injuries through public awareness. PMID- 1284002 TI - A molecular semiotic view of biology. Interferon and 'homeokine' as symbols. AB - A term "homeokine" was introduced as a generic name covering cytokines and protein hormones which serve the purpose of intercellular communication within the animal body for homeostasis and ontogenetic development. The homeokine system, in its complex way of functioning, seems to be analogous to another communication system, human language. Individual homeokine molecules are likened to words; they have meanings and are viewed as symbols, representing those conditions or events inside and outside the body which are relevant to homeostasis. Extending this view, any protein and other molecule can be considered to take on the character of sign, when integrated into a purposive system of higher hierarchy, because the molecule then represents a meaning relative to the system as a whole that is lacking in the isolated state. Living systems with their biological macromolecules as semantic units are constructed upon the principle of double articulation, just like human languages with words as the semantic units. The structure and function of a molecule (of protein and any other substance) are associated with each other, with various degrees of arbitrariness, as are the expression and the content of a sign in general. Namely the activities or the sign functions of biological molecules are determined by the organized system they belong to, and not vice versa. PMID- 1284003 TI - Transurethral prostatectomy compared with incision of the prostate in the treatment of prostatism caused by small benign prostate glands. AB - In a prospective, randomized study 60 patients with prostatism caused by small prostate glands (estimated weight < 20 g) had either transurethral prostatectomy (TURP, n = 31) or transurethral incision of the prostate (TUI, n = 29). Operating time and blood loss were significantly less in the group that underwent TUI. There were no differences between the groups in number of days with an indwelling catheter or days in hospital after operation. Eight patients in the TUI group required further operation, as did four in the TURP group, one of whom was discharged with a permanent indwelling catheter. In addition one patient developed a urethral stricture. Nine of the failures of treatment occurred within the first month. Fifty-one patients were followed up at 3 months and 47 were also seen at 12 months. Both operations significantly improved symptom scores and maximum flow rates compared with preoperatively, but the improvement in maximum flow rate was significantly better in the TURP group than in the TUI group. At 12 months TURP had also improved micturition time and voided volume, which TUI had not. Neither operation caused any significant change in sexual activity or erective potency postoperatively. Retrograde ejaculation was, however, seen in more than half of the patients in the TURP group, and only one in the TUI group. We recommend TUI for the treatment of prostatism caused by small prostate glands in patients who want to preserve normal ejaculation or are at poor surgical risk. PMID- 1284004 TI - Transcervical prostatectomy in perspective. AB - In a prospective study, 175 consecutive patients were included in transcervical prostatectomy. The results of the operation were evaluated by the mean weighted score and the postoperative morbidity. Although, urethral catheter was routinely removed on the second postoperative day, there was no evidence of suprapubic urinary fistula, clot retention or incontinence of urine noticed in any patient. Recatheterisation was required only in 2 patients for atony of the bladder muscles. Apart from wound infection in 3.4%, there was no other morbidity encountered with this technique. It is encouraging that about 77% of the patients went home before the fifth postoperative day and only one patient died on the second day. The merits of this technique have been highlighted in perspective with other studies reported in the literature. PMID- 1284005 TI - [The efficacy of propaphenol in extrasystole in patients with ischemic heart disease]. PMID- 1284006 TI - [The clinical importance of determining the endorphin level]. PMID- 1284007 TI - [Changes in antiproteolytic activity in the blood and cervical mucus after superovulation stimulation]. AB - The function of proteins, peptides, proteases and inhibitors of proteases in modulations of regulation mechanisms of gonadotrophins during the development of ovarian folicles has not been fully explained up to now. We can see difference reactions of ewes to superovulation stimulations in oestrous and anoestrous periods as shown by the variation of the antiproteolytic activity of blood plasma and cervical mucus. Trypsin is used as a model for serine protease, and trypsin inhibitory activity (TIA) was measured from the reduced rate of trypsin hydrolysis of the chromogenic substrate N-alpha-tosyl-L-arginine-4-nitroanilide (TAPA, Bartik et al., 1974). Full hydrolytic activity was determined as a change in absorbency at 405 nm = 1.0 after ten-minute incubation at 25 degrees C and pH = 8.1, and inhibition was expressed in percentage of full activity. Statistical analyses were performed by Student's t-test. Twenty-three ewes in anoestrus and twenty-eight ewes in oestrus were included in this experiment. They were of the Slovak Merino breed, two to three years old, with the mean live weight of thirty to forty kg. The ewes were treated with Ageline vaginal sponges (20 mg chlorsuperlutin/sponge) to provide for synchronization of ovarian activity, in the interval of eleven to twelve days. After removal of sponges, the ewes were stimulated for superovulation as shown in Tab. I. Heparinized blood plasma samples were stored at -25 degrees C. Low molecular TIA activities were determined in HClO4--treated blood plasma. Samples of cervical mucus were taken on cotton-wool tampons which were evaluated in 0.2 M Tris-HCl buffer, pH = 8.1. Figs. 1-6 shows TIA changes in blood plasma and cervical mucus on particular days. Fig. 7 shows the mean values of controls (I-initial) after synchronization (A) and after stimulation (S). TIA changes were different in anoestrous and oestrous periods. Differences in TIA changes in blood plasma and cervical mucus in oestrous period suggested certain local regulation mechanisms of synthesis and/or secretion of this activity in the cervix. Some values of TIA were maximum at the time of expected heat or ovulation and may be some of the factor(s) which influenced fertility of females after superovulation stimulations. PMID- 1284008 TI - [A field table-suitcase for the surgical nurse]. PMID- 1284009 TI - Developing a poster for disseminating research findings. AB - One of the goals of research should be the dissemination of research findings. Presentation of research findings to an audience of interest can be accomplished through formal or informal presentations at professional conferences or on a departmental level, publication in a variety of professional journals, and presentation as a poster session. Poster presentations attract an audience of similar interest, permit interaction and clarification of the research process and findings by the researcher, allow creative expression in presentation, and help to build collegial relationships with others who hold similar interests. Posters are also a way for educators to present the research findings of others that answer specific clinical questions or provide a means of staff development. A well-designed poster gives the viewer a concise overview of the research problem/purpose, research methodology, sample, results, and implications. Since the less formal poster presentation is viewed as less intimidating to some researchers and conference participants, posters may provide a more relaxed atmosphere in which the exchange of information takes place. PMID- 1284010 TI - Cerebellar connections of the ventral lateral geniculate nucleus in the rat. AB - The connections between the deep cerebellar nuclei and the ventral lateral geniculate nucleus (LGv) were investigated in rats using orthograde and retrograde transport of horseradish peroxidase. Following injections into the deep cerebellar nuclei there was orthograde transport to the contralateral medial LGv and adjacent zona incerta. Injections restricted to LGv consistently labelled a small cluster of cells in the contralateral posterior interposed nucleus. Injections into regions surrounding LGv produced distinctively different patterns of orthograde and retrograde labelling. PMID- 1284011 TI - Cytokinetic studies on the aortic endothelium and limb bud vascularization in avian embryos. AB - Cytokinetic studies on the aortic endothelium using the BrdU/anti-BrdU-method were carried out on 2.5- to 6-day chick and quail embryos. The mitotic activity of the aortic endothelium is related temporally to the age of the avian embryo and spatially to the embryonic region where the aorta originates. The mitotic activity of the aortic endothelium decreases with increasing age of the embryos. In the limb buds, however, the mitotic rate of the aortic endothelial cells increases independently of the age of the embryo. This increase in the mitotic activity of the aortic endothelium at the appropriate levels coincides with the vascularization of the outgrowing limb buds. We concluded therefore that the aortic endothelium probably supplies endothelial cells for the formation of limb vessels at this stage. Thus our results suggest that angiogenesis (sprouting of capillaries from pre-existing vessels) takes place during limb vascularization in avian embryos. On the other hand, immunohistochemical studies with QH-1 or MB-1 antibody show, beside a capillary network in the central core of the wing bud, individual immunolabelled cells of mesenchymal character within the primarily avascular subectodermal region from the onset of vascularization onwards. We suggest that these cells have partly to be regarded as endothelial precursor cells, which have differentiated in situ from the local limb mesenchyme, and which will contribute to the developing vascular plexus. This means that not only angiogenesis, but also vasculogenesis (in situ from mesenchymal precursors differentiated endothelial cells) appears to be involved in limb vessel formation. PMID- 1284012 TI - The effect of saffron on intracellular DNA, RNA and protein synthesis in malignant and non-malignant human cells. AB - Extract of saffron (Crocus sativis) has previously been shown to inhibit colony formation and cellular DNA and RNA synthesis by HeLa cells in vitro. In order to compare the sensitivity of malignant and non-malignant cells to saffron, we examined the effect of the extract on macromolecular synthesis in three human cell lines: A549 cells (derived from a lung tumor), WI-38 cells (normal lung fibroblasts) and VA-13 cells (WI-38 cells transformed in vitro by SV40 tumor virus). We found that the malignant cells were more sensitive than the normal cells to the inhibitory effects of saffron on both DNA and RNA synthesis. There was no effect on protein synthesis in any of the cells. PMID- 1284013 TI - Goyrand of Aix. PMID- 1284014 TI - Lessons in Dupuytren's disease. PMID- 1284015 TI - Scientific comment. Basic science of Dupuytren's disease. AB - At a cellular level, the major phenomenon in Dupuytren's contracture is an increase in proliferating fibroblasts, rather than an alteration in the type of fibroblasts. The collagen and glycosaminoglycan changes observed in the tissues of Dupuytren's contracture are likely to be secondary to changes in fibroblast density. Oxygen free radicals released from narrowed microvessels and from the fibroblasts themselves may play a role in stimulating fibroblast proliferation. Messina's experiments with continuous distraction and the success of limited fasciotomy indicate a role for physical forces in the pathogenesis of Dupuytren's contracture. The mechanism whereby physical events stimulate biochemical changes are undetermined, but preliminary investigations suggest that electrical fields and ion channels may be important. The future of Dupuytren's contracture rests with the delineation of these chemical and physical processes and their application and rigorous testing in the clinical setting. PMID- 1284016 TI - Open palm technique for Dupuytren's disease. A five-year follow-up. AB - One hundred and seven patients presenting 140 localizations of Dupuytren's disease were operated upon by a single surgeon before 1985, according to a modified Mac Cash procedure combining a Bruner approach and open transverse digital and/or palmar incisions. All surgery was performed under axillary block on an out-patient basis. A striking feature is the absence of complications such as haematoma, skin necrosis or infection. In the early post-operative follow-up (mean 105 days), the average angular improvement was 79.5% in all patients. Among the 107 patients, 54 (for a total of 67 localizations) were specifically reviewed with an average follow-up of 5.6 years. Improvement averaged 74% in 83.5% of digits. In the remaining 16.5%, the lack of extension averaged 31 degrees. Some factors had a negative effect on final results: early age of onset, major involvement of the PIP joint, localization at fifth ray level. The recurrence rate (41%, 23% of which severe) is identical to other reports on limited fasciectomy. A good indication is therefore a patient older than 50, and the method provided low postoperative morbidity and pain, associated with acceptable results. PMID- 1284017 TI - A natural history of Dupuytren's contracture treated by surgical fasciectomy: the influence of diathesis (76 hands reviewed at more than 10 years). AB - Fifty-six patients (51 males and 5 females) were reviewed more than 10 years after surgical fasciectomy for Dupuytren's disease (average 12 years 7 months). 76 hands were operated upon (20 bilateral cases) for a total of 137 fingers (out of 152 affected digits). The average pre-operative score based on Tubiana's classification was of 4.28. To-date, at maximum follow-up time, it is of 2.45. 34 recurrences occurred before re-operation (i.e. 45%), whereas at maximum follow up, 74% of hands are still defective, although only 22% cause functional impairment. The method of improvement ratio classifies patients into two categories: satisfactory results and failures. This original method of qualification emphasizes three negative factors: recurrences, initial severity of disease, and failure to achieve full finger extension post-operatively. Results as a whole are in accordance with those mentioned in literature. Improved results depend on early surgery for severe cases, which must therefore be diagnosed at an early stage. Surgery often sets back the disease, without curing it. Further efforts in fundamental research on the etiology of this disease will be needed. PMID- 1284018 TI - A mid-term review of the results of dermofasciectomy for Dupuytren's disease. AB - Clinical involvement of the palmar and digital skin by Dupuytren's disease occurs frequently. A review of 40 rays in 32 patients who had consecutively undergone dermofasciectomy is presented. The average follow-up period was 38 months, with a minimum of 24 months. Four out of the 40 rays developed recurrent nodule formation limited to the proximal or distal graft insets but there was no recurrent cord formation, suggesting better disease control than by fasciectomy alone. Full thickness graft to resurface the defect has been surprisingly complication-free. PMID- 1284019 TI - Dermofasciectomy: a long term review. AB - Thirty-two dermofasciectomies in 24 cases were reviewed with an average of thirteen years for follow-up. These were compared with the same patients followed up ten years earlier. A marked increase in extension of the disease from 24% to 79% was noted. The recurrence rate has remained constant at 47% and only two recurrences were found under the skin graft. This procedure must, therefore, remain the operation of choice in the management of aggressive Dupuytren's disease. PMID- 1284020 TI - Compartment syndrome of the scapula. Definition on clinical, neurophysiological and magnetic resonance data. AB - Compartment syndromes of the scapula and pelvic girdle have received scant attention in the literature. In 1938, Comolli first described a clinical sign which he considered specific to fracture of the scapula. We report data on two patients, one presenting with prolonged pressure on the posterior surface of the scapula and the other with symptoms associated with scapular fracture. In one of these patients we were able to measure pressures around the scapula, perform neurophysiological assessment of nerve function and produce magnetic resonance images of the area. In the other case, surgical exploration revealed an established ischaemic contracture of the infraspinatus muscle within its compartment. These findings suggest that the muscles around the scapula are vulnerable to the development of compartment syndrome. PMID- 1284021 TI - Ultrasonography of the normal and abnormal antenatal development of the upper limb. AB - The degree of severity of congenital deformities of the hand, as well as any coexisting congenital anomaly should be evaluated especially if there is a possibility of therapeutic termination of pregnancy. This may be relatively easy in the case of some major malformations which affect the neurological or intellectual capacity of the child. It is however more difficult in the presence of predominantly motor anomalies, and with distally based anomalies of the upper limb which may be amenable to later reconstructive surgery. PMID- 1284022 TI - Forty-eight glomus tumours of the hand. Retrospective study and four-year follow up. AB - We report a series of 48 glomus tumours of the hand, which have been reviewed with an average follow-up of 4.5 years (2-14). The tumour was nearly always sited in the distal digit, para-ungual (22 cases), more rarely subungual or under the pulp, with an even distribution among the fingers. Diagnosis was made preoperatively in 37 of 47 tumours of the digits, based on clinical features: consistent eliciting of pain by touch, less often by chill and occasionally accompanied by vasomotor phenomena. The pain and therefore the tumour could be accurately located with the tip of a pencil (Love's sign); these symptoms are abolished by inflation of a tourniquet proximally (Hildreth's sign). In 40% of cases a small defect in the distal phalanx is visible on plain radiographs, as well as an enlargement of the subungual tissues when the tumour is dorsal. The surgical approach was usually para ungual, in a sub-periosteal plane. Tumours were small (3.3 mm) and rarely multiple (3 cases). In 46 cases the pain was relieved quickly and definitively. Two true recurrences occurred after 5 years, without a satisfactory explanation. Except for those cases with transungual approach, there was no aesthetic compromise. We maintain that careful clinical assessment provides the diagnosis in most cases. Plain radiographs, lateral and comparative, are useful. MRI scan may occasionally prove of diagnostic value. The lateral ungual approach permits complete excision and healing. Recurrence is rare. PMID- 1284023 TI - Idiopathic avascular necrosis of the scaphoid. A case report. AB - A single case of non-traumatic, idiopathic avascular necrosis of the carpal scaphoid is presented. It permits an informative correlation of clinical evolution. X-ray appearance, MR-imaging, macroscopic aspect and histological findings. PMID- 1284024 TI - Combined second toe and partial nail transfer from the big toe by means of an exteriorized pedicle. AB - The hand of a three-year old girl was reconstructed by means of a bilateral second toe transplantation following traumatic amputation of all five digits. In a second operation, aimed at reconstructing the index finger, the nail apparatus of the big toe was transferred to the thumb as an "island flap" based on a pedicle from the second toe. The thumb was subsequently lengthened enabling a three-fingered hand to be obtained with only minimal functional impairment of the feet. The authors suggest an original technique allowing transfer of the second toe and of the big toe nail in only one operative stage. The technique of leaving the pedicle exteriorized during transplantation (autonomization) facilitates positioning of the nail onto the recipient site and eliminates subsequent problems of commissural retraction. PMID- 1284025 TI - A palmar plaque and flexor tenosynovitis in a patient with sarcoidosis. AB - Involvement of the soft tissues of the hand by sarcoidosis is rare. We report a patient with sarcoidosis who presented with a large subcutaneous plaque of the palm and flexor tenosynovitis of the middle finger. PMID- 1284026 TI - The role of fibroblast growth factors and related oncogenes in tumor growth. PMID- 1284027 TI - Angiogenesis: a mechanism by which oncogenes and tumor suppressor genes regulate tumorigenesis. PMID- 1284028 TI - The ubiquitous transactivator Zfp-38 is upregulated during spermatogenesis with differential transcription. AB - We describe the complete nucleotide sequence of a full length cDNA clone encoding a new mouse zinc finger protein gene, Zfp-38 and localize it on chromosome 5 by the interspecific backcross analysis. The N-terminal domain of the Zfp-38 protein (64 kDa) contains 358 amino acids and the C-terminal domain of 197 residues encodes 7 zinc fingers. We also present evidence that Zfp-38 is a strong transcriptional activator. The transactivation domain was localized in the non finger region and a fusion protein containing 112 amino acid residues from this region of the Zfp-38 and the DNA binding domain of the yeast Gal 4 protein, very efficiently transactivated the expression of a reporter CAT plasmid, harboring the Gal4 target site. By in situ hybridization and northern blotting technique, the Zfp-38 transcript can be detected at a highly elevated level during spermatogenesis. Its expression accompanies the progression from pachytene spermatocytes to round spermatids. The undifferentiated spermatogonia or the haploid elongated spermatid and the spermatozoa do not show any detectable level of the transcript. Interestingly, other tissues express low levels of a slightly shorter transcript with a different 5' end as determined by RNase protection. The presence of both a transcriptional activating domain and 7 DNA binding zinc fingers, coupled with the cell type(s) specific expression pattern, suggests that Zfp-38 has the potential to regulate transcription during spermatogenesis. PMID- 1284029 TI - The cloning and characterization of a localized maternal transcript in Xenopus laevis whose zygotic counterpart is detected in the CNS. AB - We have cloned a cDNA (xlan4) from a Xenopus laevis oocyte cDNA library whose cognate mRNA is localized in the animal pole region of full grown oocytes. The cDNA can be translated in vitro to produce a predicted size protein of 35 kDa and, is also expressed in E. coli as a fusion protein. The conceptual protein encoded by the xlan4 cDNA is 17.5% proline rich and possesses several PEST sequences found in proteins with short half-lives. The xlan4 mRNA is 2.6 kb and during early development its titer decreases until the neurula stage after which it begins to reaccumulate. Northern blots on dissected embryos and in situ hybridization revealed that the zygotic expression is limited to the dorsal axial structures consisting primarily of the CNS. UV irradiation of the vegetal pole region immediately following fertilization that produces ventralized embryos results in a loss of zygotic xlan4 expression. In the adult, xlan4 mRNA is limited primarily to the brain. The presence of this mRNA in animal pole region which contributes to the future neural cell lineages suggests that this gene product may function either in the specification of neural cell types or in a neural specific function. PMID- 1284030 TI - Effects of calcium channel agonism by Bay-K-8644 on ventricular fibrillation threshold of isolated heart. AB - The hypothesis tested was that enhanced entry of calcium into cardiac cells would increase the susceptibility to ventricular fibrillation as measured by the ventricular fibrillation threshold (VFT) of the isolated perfused rat heart. Bay K-8644 was used as a calcium-channel agonist. There was a biphasic effect with a maximal increase in left ventricular systolic pressure and oxygen uptake at a concentration of 10(-7) M. The same concentration caused a major reduction in the VFT. The bell-shaped pattern of fall of the VFT was inversely related to the effect on LV developed pressure. The changes in VFT could be dissociated from those on myocardial metabolites. Although Bay-K-8644 increased the heart rate, reduction of the VFT could also be obtained in paced hearts. The addition of ryanodine, an agent known to interrupt intracellular recycling of calcium through the sarcoplasmic reticulum, was able to abolish approximately half the effect of Bay-K-8644 on the VFT. Therefore, increased entry of calcium via the calcium channel is able to reduce VFT, acting in part through enhanced recycling of calcium through the sarcoplasmic reticulum. PMID- 1284031 TI - Collateral formation after repeated transient dearterialization of the rat liver. AB - Hepatic artery ligation is used for the palliation of patients with malignant liver tumours. Collaterals are developed rapidly and could to some extent explain why the growth is affected for only a short period. With intermittent dearterialization, collaterals seem to be avoided and possibly a more extended effect should be expected. The most efficient period of dearterialization to avoid collaterals was studied in this experiment. Five groups of rats were treated with daily repeated transient dearterializations for 0 (n = 3), 60 (n = 6), 120 (n = 6), 180 (n = 6) and 240 minutes (n = 6) respectively for 5 days and compared to another group (n = 3) that was permanently dearterialized. After treatment, celiac angiograms were obtained. All hepatic arteries were reliably occluded and patent after 5 days of daily blockades in all but two rats. There were no collaterals demonstrable on the angiograms in the first four groups after 5 days of intermittent obstruction of the arterial blood flow to the liver. After 240 minutes of dearterialization as well as after collaterals developed and were clearly demonstrated on the angiograms after six days. Liver enzymes were normal even after 4 hours of dearterialization. Repeated occlusions of the hepatic artery was reliably achieved with the implantable minioccluder. Repeated, transient dearterializations for 1, 2 or 3 hours could be performed without development of collaterals and without damage to the liver. PMID- 1284032 TI - Pulmonary injury in acute experimental pancreatitis correlates with elevated levels of free fatty acids in rats. AB - Since some authors have stated a certain role for so-called "free fatty acids" (FFA) in the pathogenesis of AP and the subsequent systemic complications we tried to find possible correlations between FFA, pancreatitis and lung injury using a rat model. AP was induced by intraductal infusion of two different concentrations of glycodeoxycholic acid (GDOC 17 mmol and 34 mmol). An equal number of animals had only cannulation of the pancreatic duct without infusion and served as controls (GDOC-control). In another experimental model iv.-infusion of oleic acid (OA) was used to create severe lung injury comparable to human ARDS. In this model control animals received iv.-infusion of saline solution only (SAL). At 2, 6, 12, 24 and 48 hours the animals were sacrificed and blood was collected for determination of FFA, amylase and pO2. The pancreas and lungs were removed for histologic examination and the lungs were weighed. GDOC-34 animals developed severe pancreatitis with hemorrhage and necrosis. Histology of the lungs showed edema, inflammatory infiltrates, hemorrhage and thickening of the alveolar membrane in GDOC-34 rats as well as in OA-animals. In contrast, there was only pancreatic edema until 24 hours in the GDOC 17 group and less severe histological changes in the lungs. Amylase, FFA, pO2 and lung weight were directly influenced by the different kinds of treatment. Furthermore, FFA correlated positively with the levels of amylase and lung weight and negatively with pO2. Infusion of OA alone also caused an increase in levels of amylase with pancreatic edema and focal necroses in some animals. These results show that it was possible to create different degrees of severity of AP which was in concordance with different degrees of morphologic changes and dysfunction in the lungs. FFA values correlated significantly with the clinical course as well as with increasing amylase, lung weight and decreasing pO2. PMID- 1284033 TI - [Bleomycin emulsion for intralesional instillation in advanced oropharyngeal carcinomas. A case report on local bleomycin application]. AB - Local therapy of head and neck cancer using a special bleomycin emulsion as an intratumoral applicarted cytotoxic agent is not established in regular antitumor therapy. It's use only is supposed to be regarded as an "ultima ratio" possibility when other usual methods like surgery, radiotherapy or systemic cytostatic therapy have failed. The procedure of intralesional bleomycin emulsion application will be described and the advantages and disadvantages will be discussed by means of a long-term case report. PMID- 1284034 TI - Contrasting effects of interferon gamma and interleukin 4 on responses of human vascular endothelial cells to tumour necrosis factor alpha. AB - Tumour necrosis factor alpha (TNF-alpha) and interleukin 4 (IL-4) selectively synergise in inducing expression of the mononuclear cell adhesion receptor VCAM-1 (vascular cell adhesion molecule-1) on human umbilical vein endothelial cells (HUVEC), which results in increased adhesiveness of HUVEC for T lymphocytes. This process may be crucial for adherence of circulating lymphocytes prior to their passage from the blood into inflammatory tissues. IL-4 also amplifies production of interleukin 6 (IL-6) and monocyte chemotactic protein-(MCP-1) from TNF-alpha activated HUVEC. In the present study we demonstrate that IL-4 enhances production of granulocyte-macrophage colony-stimulating factor (GM-CSF) from TNF alpha-stimulated HUVEC. Moreover, using cultured adult saphenous vein and umbilical artery endothelial cells, we show identical effects of IL-4 on TNF alpha-induced responses to those observed with endothelial cells of foetal origin. Additionally, we report here that TNF-alpha and interferon gamma (IFN gamma) synergise in the induction of both the lymphocyte adhesion receptor VCAM 1, and the TNF-alpha-inducible neutrophil adhesion receptor intercellular adhesion molecule-1, on all three endothelial cell types studied. In contrast, we found that GM-CSF secretion by endothelial cells treated with IFN-gamma plus TNF alpha was markedly decreased when compared to the response induced by TNF-alpha alone. These results suggest that the combined actions of several cytokines, acting sequentially or in concert, may exert differential effects on activation and accumulation of circulating lymphocytes at sites of inflammation. PMID- 1284035 TI - Derivation of a monoclonal anti-murine IL-4 antibody specific for an epitope expressed on denatured molecules. AB - Monoclonal antibodies to interleukin 4 (IL-4) were generated by immunization with recombinant IL-4 and screening by binding to IL-4 adsorbed to plastic surfaces. Three antibodies were obtained that scored well in this assay and one, 13E1, was studied in detail. It was very effective in detecting IL-4 by Western blotting whereas a neutralizing anti-IL-4 antibody, 11B11, was 50-100-fold less sensitive as a detecting agent. Sequential immunoprecipitation and biosynthetic labelling studies indicated that the 11B11 and 13E1 epitopes are largely expressed on different forms of IL-4. 13E1 was able to detect cytosolic IL-4 both by immunohistochemical and flow cytometric analysis of fixed cells. This was routinely successful in an insect cell line (Sf9) expressing large amounts of IL 4 as a result of infection with a recombinant 'IL-4 baculovirus'. Although stimulated D10 cells could also be shown to express IL-4 in their cytosol, positive results were not obtained in all such studies and we have failed to detect IL-4 production by normal T cells using this method. This antibody may have substantial value in detecting IL-4 by Western blots and as a tool to analyze the biosynthesis of IL-4. With suitable improvement in sensitivity, it also may prove valuable in the detection of IL-4 in the cytosol of individual cells. PMID- 1284036 TI - Serum granulocyte colony-stimulating factor levels in umbilical cord blood of normal full-term neonates. AB - We measured granulocyte colony-stimulating factor (G-CSF) levels in cord blood of 59 normal full-term neonates immediately after birth and the subsequent changes in G-CSF levels of 16 cases by our modified enzyme-linked immunosorbent assay (ELISA) for G-CSF. Ten out of 59 cases examined (17%) showed G-CSF levels in cord blood after delivery between 20 and 57 pg/ml, although in the remaining cases, the G-CSF levels were below 20 pg/ml, which was our minimal detection level. A direct relationship between G-CSF levels and white blood cell count, absolute granulocyte numbers in cord blood, gestation age or weight was not observed. Although G-CSF levels in cord blood after delivery remained below 20 pg/ml in 5 cases out of 16 tested, those in the remaining 11 cases (69%) subsequently became elevated after delivery. The peak G-CSF level in cord blood after delivery ranged from 26-364 pg/ml, and the time of it was between 4.5 and 18 h. As G-CSF level per wet weight of placenta was high (124 x 29 pg/ml), these subsequent elevations of G-CSF in cord blood after delivery may result from a gradual influx from the placenta. PMID- 1284037 TI - [Monoaminoxidase activity and serotonin metabolism in the brain of rats during latent inhibition]. AB - The monoamine oxidase (MAO) activities and the concentrations of 5-HT and 5 hydroxyindoleacetic acid were investigated in four brain regions in rats during the acquisition of latent inhibition in one-trial passive avoidance task. 5-HT metabolism was not altered in the hippocampus. Changes of 5-HT metabolism were found in the frontal cortex during testing of latent inhibition and were accompanied by lowering of MAO activity. No change of 5-HT metabolism was observed in this structure at the stage of pre-exposition to conditioned stimulus. 5-HT metabolism was activated at the stage of pre-exposition to conditioned stimulus in the amygdala and striatum and was maintained on high level, in these structures during testing of latent inhibition. The data presented here indicate that serotoninergic system in various brains regions is specifically involved in the formation of different stages of latent inhibition. PMID- 1284038 TI - [Emoxipin as an inhibitor of angiogenesis]. AB - The effect of emoxypin on angiogenesis in rabbit cornea in aseptic inflammation induced by intracorneal implantation of a piece of quartz and on the development of the vessels of the chick embryo yolk sac was studied. 1% emoxypin pipetted thrice a day for 10-14 days inhibited corneal neovascularization and reduced the formation of new blood vessels. We observed an inhibitory effect on the development of vascular bed of the embryo yolk sac on incubation hour 64-72. The drug affected neither general growth of the embryos no the number of somites. PMID- 1284039 TI - [The immunodiagnosis of thrombocyte membrane glycoprotein deficiencies: Glanzmann's thrombasthenia, Bernard-Soulier syndrome and GMP-140 protein deficiency]. AB - Immunological methods were developed for the diagnosis of platelet membrane glycoprotein (GP) deficiencies. The number of membrane GP on platelet surface was determined as the binding of 125I-labeled monoclonal antibodies (mAB) directed against individual platelet GP. Total amount of GP in platelet lysate was assessed by immunoblotting with specific polyclonal antibodies. Methods were applied for patients with different thrombocytopathies. Binding of mAB VM16a, directed against GP IIb-IIIa was strongly decreased in patients with Glanzmann's thrombasthenia (0.5-14.5% of normal) and binding of anti-GP Ib mAB VM16d--in patient with Bernard-Soulier syndrome (0.5% of control) indicating the deficiencies of corresponding GP. In patient with gray platelet syndrome binding of both antibodies was not decreased but even increased. It was shown by immunoblotting that platelets from the patient with gray platelet syndrome contained normal amount of GP IIa, but strongly decreased amount of GMP-140 (14.5% of control)--membrane GP of platelet--granules. PMID- 1284040 TI - The zonal expression of alpha-fetoprotein transgenes in the livers of adult mice. AB - The developmental regulation of the alpha-fetoprotein (AFP) gene in liver results in high-level expression in the fetus, followed by dramatic transcriptional repression after birth. We have examined the mouse AFP gene for transcriptional control sequences that may be involved in its postnatal repression in liver. We showed previously that removal of a DNA region between positions -250 base pairs (bp) and -838 bp of the AFP gene resulted in the persistence of expression of an AFP minigene in the postpartum liver of transgenic mice (Vacher and Tilghman, Science 250:1732-1735, 1990). This study examines the distribution of these transgene transcripts in liver using in situ hybridization. We show that there is a zonal distribution of minigene transcripts in the adult livers of these animals. Hepatocytes surrounding the central veins express high levels of minigene transcripts, while hepatocytes in the intermediate and portal areas contain few, if any, transcripts. Quantitative RNAse protection analysis shows a decrease in transgene RNA levels after birth, consistent with repression in all but a small subset of hepatocytes. These results indicate that repression in the pericentral hepatocytes is dependent upon the presence of a cis-acting, negative regulatory domain, which is located between the enhancers and the proximal promoter of the AFP gene. In contrast, this domain is not essential for complete repression of AFP transgenes in the intermediate zone and periportal hepatocytes. PMID- 1284041 TI - [Prognostic factors, late relapse and outcome of patients with aggressive malignant lymphoma: long term results of LNH-80 protocol]. AB - The 100 patients with aggressive malignant non Hodgkin lymphoma treated with the LNH-80 regimen were evaluated for long-term survival and quality of life. The LNH 80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two patients are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. Factors adversely correlated with response in multivariate analysis were poor performance status, bone marrow involvement and the presence of more than one extranodal site. Factors adversely correlated with survival were age, high grade subtypes, and bone marrow involvement. The fifty-two long-term responders were evaluated for quality of life parameters such as working ability, sexual function, fertility and absence of long-term sequelae. Of the 41 patients who worked before disease, 66% had resumed their normal job and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) considered having mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had a second neoplasia. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity. PMID- 1284042 TI - Poly(L-lysine)-conjugated oligonucleotides promote sequence-specific inhibition of acute HIV-1 infection. AB - Previously, we have reported that conjugation of antisense oligonucleotides to poly(L-lysine) (PLL) lowers their inhibitory concentration in several biological models. We have now tested these conjugates for inhibition of human immunodeficiency virus type 1 (HIV-1) replication. PLL-conjugated oligonucleotides complementary to the translation initiation site of Tat protein protect cells from the cytopathic effect of HIV-1 in acute infection assays. The EC50 of conjugates is approximately 0.15 microM, which represents a strong reduction in concentration as compared to nonconjugated oligonucleotides (EC50 = 20 microM). In contrast with most reports in the literature, we have observed sequence specific antiviral effects with PLL conjugates. This was particularly noteworthy in antiviral experiments performed with HIV-1 isolates presenting heterogeneity in the 5' end of the tat mRNA sequence. Two mismatches at the target site were sufficient to reduce very significantly the antiviral activity of the conjugates but did not modify the effect of nonconjugated oligonucleotides. Unlike free oligonucleotides, PLL-conjugated ones do not interfere with virus penetration and/or reverse transcription as demonstrated by polymerase chain reaction (PCR) analysis of viral DNA. PMID- 1284043 TI - Potentiation of radiation lethality in mouse melanoma cells by mild hyperthermia and chloroquine. AB - To test the hypothesis that radiosensitization by combined mild hyperthermia and chloroquine may be increased by the presence of melanin in treated cells, Cloudman melanotic mouse melanoma S91/6 cells, and the amelanotic S91/amel cells were incubated during a 3 h post-irradiation period with 0.03 mM chloroquine at 41 degrees C. A considerable increase in radiation lethality was observed (radiation potentiation factor > 1.6) in both cases. Addition of 0.1 mM isobutyl methyl xanthine (IBMX), a promoter of melanin synthesis, to the growth medium of S91/6 cells 10 days before irradiation, did not further increase the lethality of radiation followed by combined heat and chloroquine treatment. Under these conditions, toxicity to unirradiated cells was slight. On the other hand, 10 microM chloroquine showed similar toxicity to unirradiated B-16 mouse melanoma cells, but did not increase radiation lethality. Factors other than melanin content therefore play a role in the potentiation of radiation lethality by mild hyperthermia and chloroquine. PMID- 1284044 TI - [Effect of immunosuppressants FK506 and rapamycin on the function of progesterone receptor: protein "p59-HBI", intersection between immunology and endocrinology?]. AB - In the absence of hormonal ligand, inactive, heterooligomeric, 8-10S steroid receptor complexes include a p59 protein (apparent M(r) approximately 59 kDa) bound to th heat shock protein hsp90 (apparent M(r) approximately 90 kDa), which itself binds to the ligand binding domain LBD of the receptor molecule, p59 is thus an hsp binding immunophilin HBI, which, through its interaction with a chaperone, may intervene in several cellular functions. We report that, in cell free experiments at 0 degrees C, FK506 and rapamycin do not release p59 nor hsp90 from the 9.5S rabbit uterus progesterone receptor, suggesting that the binding of p59 to hsp90 does not interfere with the rotamase site of HBI. There is no "transformation/activation" of the receptor, but an up to 2 fold increase in progesterone agonist and antagonist binding to the receptor is observed. It is suggested that a functional interaction between HBI and receptor activity may be mediated by hsp90. PMID- 1284045 TI - The application of immunocytochemistry in diagnosis of meningeal carcinomatosis in a patient with unknown primary site. AB - A 55-year-old female with meningeal signs was suspected to have carcinomatosis meningitis based on cytospin cytology study of cerebrospinal fluid (CSF) with Wright stain. There was no primary site of any malignancy which could be identified as the source of metastasis. Immunochemical staining for cytokeratin and carcinoembryonic antigen on suspicious large immature cells in the CSF gave positive results and confirmed the malignant nature of her disease. Intrathecal chemotherapy with methotrexate and whole brain irradiation then eradicated the symptoms rapidly. Immunocytochemistry was considered to be a very powerful diagnostic tool in management of this patient. PMID- 1284046 TI - Systemic and regional oxygen uptake and lactate flux in endotoxic dogs resuscitated with dextran and dopexamine or dextran alone. AB - We examined how volume resuscitation with and without dopexamine, a potent beta 2 adrenergic and dopaminergic agonist, would affect O2 uptake (VO2), O2 delivery (DO2), and lactate metabolism in whole body, skeletal muscle, and gut of 18 anesthetized dogs after they were infused for 1 hr with 2 mg/kg endotoxin. Six dogs were then infused with dextran for 2 hr at 0.5 ml/kg/min (DEX); another six were given the same volume with 12 micrograms/kg/min dopexamine (DPX); and a third group received no treatment (NT). After endotoxin, all animals were hypotensive; cardiac output decreased 30%; and DO2 to whole body, skeletal muscle, and gut were at or below critical for VO2. DO2 was raised above critical in whole body and gut of DEX and DPX but not in muscle of DPX, which produced lactate. Whole body DO2 approached preendotoxin level by 2 hr in DEX and DPX but stayed near critical in NT. At that time, gut VO2 was higher in DPX than in DEX or NT, and lactate efflux became less than in DEX. Vascular reactivity was present in the gut at the end of the experiment in six of six DPX studies, in four of six DEX studies, and in none of the NT studies. These results suggest that resuscitation with dopexamine + dextran after induction of endotoxic shock may be more beneficial than dextran alone, particularly for the gut mucosa. PMID- 1284047 TI - Inhibition of histamine release and pressure increase induced by endothelin (ET 1) in isolated rat kidneys treated with propionyl carnitine. AB - Endothelin-1 (ET-1) is an amino peptide produced by endothelial cells with a potent vasoconstrictor activity; this effect is regulated by a release of other endogenous vasal factors. Recent studies have demonstrated that endothelin is capable of releasing from different tissues, and particularly from perfused organs such as spleen and kidney, many vasal factors and prostanoids. The present study investigates whether perfusion with a solution of endothelin-1 in rat isolated kidney can induce the release of histamine, another vasal factor (until now not investigated in relation with endothelin-1) and whether treatment with propionyl carnitine, a compound with vasoprotecting activity, inhibits this release. This research demonstrates that histamine released by rat kidney perfused with endothelin is lowered if previously treated with propionyl carnitine. This effect of propionyl carnitine can be considered to be another important factor in a complex mechanism involved in its vasoprotective and cardiovascular action. PMID- 1284048 TI - Chemotherapeutic approaches to human immunodeficiency virus infections. AB - Since the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immune deficiency syndrome (AIDS), various attempts have been made to control this fatal disorder. In the replicative cycle of HIV, several steps have been identified as attractive targets for antiviral chemotherapy. Sulfated polysaccharides can block the virion binding to the CD4 receptor. 2',3' Dideoxynucleosides including 3'-azido-3'-deoxythymidine (AZT) act as potent inhibitors of reverse transcriptase after intracellular phosphorylation. Only AZT and 2',3'-dideoxyinosine are available so far for the treatment of AIDS and AIDS related complex. Non-nucleoside reverse transcriptase inhibitors of HIV-1 and viral protease inhibitors are the new classes of compounds that are now extensively studied. These compounds may add a new dimension to the prospects of anti-AIDS chemotherapy. PMID- 1284049 TI - False positive reaction of heat-inactivated sera in enzyme-linked immunosorbent assay for antibody to hepatitis C virus. AB - Specimens were heated at 56 degrees C or 62 degrees C to analyze the mechanisms of false positive reactions in the Ortho enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to hepatitis C virus (HCV). The highest correlation was obtained between the difference in HCV antibody titer of 56 degrees C-heated and native sera and IgG concentration. Monoclonal IgG gammopathy sera developed marked increases in the titer by preheating. However, slight increases after preheating were observed in monoclonal IgA gammopathy sera. Similar increases in the titer by preheating were also demonstrated in immunoglobulin products containing IgG. Direct bindings of denatured IgG with C100-3 and 5-1-1 antigens were shown in recombinant immunoblot assay (RIBA). These results could show the participation of denatured IgG in the false positive reaction in Ortho-HCV-ELISA. Caution is necessary in evaluating the anti-HCV antibody titers of heat-inactivated sera. PMID- 1284050 TI - Management of malignant germ cell tumours of ovary. AB - Ten patients of the advanced malignant germ cell tumours of the ovary were treated by cisplatin based combination chemotherapy after initial conservation surgery. Eight patients completed course containing cisplatinum, vinblastine and bleomycin. Five patients (62.5%) achieved CR while 2 (25%) attained PR. One patient died due to tumour lysis and respiratory infection. Rest two patients did not turn up in follow up. Long term follow up indicates above regimen to be highly effective. However poor performance status, advanced stage of disease and post operative gross residual disease were poor prognostic factors in our patients. PMID- 1284051 TI - Alpha-fetoprotein production by rhabdomyosarcoma of the urinary bladder. AB - Alpha-fetoprotein has emerged as a useful diagnostic tool for hepatic tumour and tumours of germ cell origin. However, isolated case reports of association of this tumour marker with tumours of the lung and non-germ cell tumours of the ovary are reported. We present a case of a Rhabdomyosarcoma, a generally non secretory tumour that showed raised levels of AFP in serum and reacted positively for the same in a PAP technique for AFP. Cross striations were visible in many cells on II & E stained sections. PMID- 1284052 TI - Fine needle aspiration cytology in the diagnosis of prostatic enlargements. AB - One hundred patients with enlarged prostate were subjected to fine needle aspiration cytology and histopathologic examination of prostate. The results have been found encouraging. The cytodiagnostic accuracy rate was 99 p.c. in identification of benign or malignant nature of the lesions and 94 p.c. in cytologic specific diagnosis (exactly similar to histopathologic diagnosis). The technique was simple, rapid, economical, reliable, easy to repeat and highly suitable for outpatients. The procedure can routinely be adopted in places where facilities for preparation of paraffin section do not exist or when quick diagnosis is required. PMID- 1284053 TI - Plasmodium falciparum invades human red cells via a parasite produced glycosidase. AB - This report describes that P. falciparum produces a neuraminidase like activity on invasion into erythrocytes in culture on the basis of biochemical and immunological investigations. This activity in turn modifies the surface glycoprotein receptors of red cells and may be of help in the inhibition of further invasion by merozoites. The characterization of this enzyme activity may help elucidate the mechanism of cerebral malaria. PMID- 1284054 TI - A search for immunocontraceptive agent from marine sources--role of antispermatheca globulin of Telescopium telescopium on fertility regulation in male rat. AB - Polyclonal antisera were developed in rabbits against 'spermatheca', the reproductive gland of T. telescopium, a marine mollusc. The gland contains spermatozoa. Antisera and its IgG fraction (ASTG) indicated common antigenic determinants by immunodiffusion and had titer values 81920 and 1280 against crude antigen extract. Cycling female rats when exposed to passively immunized male rats with different doses of ASTG, had reduction in implantation sites and litter size. Females had pseudopregnancy when exposed to higher doses of immunized males and had normal cycle after 20 days in average. ASTG in male rats caused decrease in weight of the reproductive glands, alteration in sperm concentration, motility and morphology, formation of multinucleated giant cells and vacuoles leading to arrest of spermatogenesis and reduction in seminiferous tubular diameter. The effects were dose dependent with reversible infertility. The results indicate presence of a common antigenic determinants which cross-react with vertebrates and existence of common relation through phylogenetic evolution and their immune responses. PMID- 1284055 TI - Effect of lysine residue modification of ovine luteinizing hormone by heterobifunctional crosslinking reagent SPDP on subunit-subunit association, receptor binding and biological activity. AB - The increasing use of heterobifunctional crosslinking agent in the design of hormone-carrier conjugates for selective targeting or inducing immune response against the hormone has prompted us to study the effect of epsilon-NH2 group modification of oLH-subunit, their recombination, immunoreactivity, receptor binding and biological activity. The epsilon-NH2 groups of oLH alpha and oLH beta subunits were modified by using SPDP. The SPDP modified oLH alpha derivatives hybridize to native OLH beta as judged by RP-HPLC analysis. The sequential modification of alpha and beta subunits led to progressive reduction in immunoreactivity and receptor binding activities. The steroidogenic potential of oLH beta.SPDP.alpha oLH recombinant was relatively comparable. The modification of six or more epsilon-NH2 groups in oLH alpha although recombine fully with native oLH beta but failed to react to anti-oLH antibody. Moreover, steroidogenic activity was also abolished. Introduction up to four SPDP groups in oLH alpha compromised immunological and biological activities but further addition of two more SPDP groups completely abolished antibody reactivity, receptor binding and steroidogenic activity indicating the importance of later two -NH2 groups in the receptor recognition and steroidogenic potential. PMID- 1284056 TI - Termination of pregnancy in mice following antiserum administration to modified chicken riboflavin carrier protein. AB - Rabbit antibodies to native riboflavin carrier protein (RCP), are to a large extent directed towards conformational epitopes and antibodies to disulphide bond reduced carboxymethylated RCP (RCM-RCP) are towards sequential epitopes. The major cyanogen bromide (CNBr) fragments and tryptic fragments of RCM-RCP interact with both antiserum to RCM-RCP and RCP. Passive immunization of pregnant mice with antibodies to RCM-RCP results in bioneutralization, leading to termination of pregnancy. Recently, a major tryptic fragment of RCM-RCP (24 +/- 2 kd) which could assume conformation at the antibody combining site of native RCP, obtained following mild trypsinization has been identified [Natraj et al. J. Biosci, 15 (1990) 341]. Rabbit antibodies to RCM-RCP treated with trypsin generated antibodies of low titer which interacted with RCM-RCP as well as RCP. The interaction of this antibody with RCP was of high affinity and could be displaced with RCP. The bioneutralizing ability of the antibody was demonstrated by its ability to cause termination of pregnancy in mice. PMID- 1284058 TI - Close correlation between hepatitis C virus serology and polymerase chain reaction in chronically infected patients. AB - To determine whether the persistent presence of antibodies to recombinant antigens of the hepatitis C virus (HCV) corresponds to the presence of hepatitis C virus RNA in the same serum, 85 anti-HCV positive patients were studied by the polymerase chain reaction (PCR). The focus of the research was on patients with chronic hepatitis. Eighty- three patients were found to be positive by PCR; only two were negative. In addition, liver biopsies taken from seven patients positive for anti-HCV were shown to contain HCV-specific RNA. Sera collected from three patients suspected to have NANB hepatitis on the basis of clinical symptoms were negative both for HCV antibodies and HCV RNA. The correlation between HCV antibody positivity and detection of HCV RNA was 97.6%. PMID- 1284057 TI - Hepatitis C virus infection in patients with acute hepatitis B. AB - The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied using a second-generation ELISA test in 121 patients with self-limiting acute hepatitis B, including 63 intravenous drug addicts (IVDA). Within the first month after the onset of illness, 47.1% of the patients were anti-HCV positive, this figure reaching 52.1% six months later. The prevalence in the sixth month was significantly higher in the IVDA (93.6%) than in the non-IVDA (6.9%) (p < 0.00001). Among the IVDA, anti-HCV was more frequent in those with (100%) than in those without hepatitis delta virus (HDV) coinfection (84.6%) (p = 0.004). Of the 63 anti-HCV positive patients, 36 (57.1%) continued to exhibit abnormal transaminase levels for more than six months, while this was not observed in anti HCV negative patients. These results show a high prevalence of infection by hepatitis C virus (HCV) in IVDA with acute B hepatitis. As a rule, infection by HCV occurred prior to the hepatitis B infection, although occasionally simultaneous infections were observed. HCV appears to be the agent responsible for chronic liver disease in patients with acute B hepatitis who become HBsAg negative. PMID- 1284059 TI - Characterization of a neutralizing monoclonal antibody to the external glycoprotein of HIV-1. AB - The major neutralizing epitope on the external glycoprotein of HIV-1 was studied with an envelope-specific monoclonal antibody and with a human serum positive for antibodies to HIV-1 proteins, both of which were able to neutralize virus infectivity. The monoclonal antibody reacted specifically with gp120 from HIV 1IIIB, and was shown to neutralize infection of CEM cells by cell-free virions, and inhibited the formation of syncytia normally observed when uninfected cells are cocultured with HIV-1-infected cells. Similar neutralization of viral infection and inhibition of syncytia formation was also demonstrated by the HIV-1 antibody-positive human serum. By examining a number of overlapping peptides from a region of HIV-1 gp120 known to contain a neutralizing epitope, this epitope was localized between amino acids 307 and 320 (V3 loop) in the external glycoprotein molecule. The monoclonal antibody did not interfere with the binding of gp120 to CD4, or with the subsequent step of CD4-induced shedding of gp120 from the viral envelope. However, it blocked the proteolytic cleavage of the V3 loop by thrombin, suggesting that the antibody may be inhibiting the interaction of the loop with other membrane-bound proteins. PMID- 1284060 TI - Enzyme and immunohistochemical assessment of myocardial damage after ischaemia and reperfusion in a closed-chest pig model. AB - The usefulness of different enzyme and immunohistochemical stains to distinguish reversible and irreversible myocardial cell injury after experimental coronary artery occlusion of varying duration and reperfusion with or without superoxide dismutase as adjunct was investigated. Biopsies or parts of the infarcted and non infarcted area were rapidly frozen and sectioned in series for enzyme and immunohistochemical evaluation. Sections were stained for the demonstration of phosphorylase, myofibrillar ATPase and mitochondrial oxidative enzymes and also with periodic acid-Schiff, alizarin red S and routine histological stains. Other sections in series were stained with antibodies against fibronectin and the intermediate filament proteins desmin and vimentin. In 49 biopsies a blind quantitative estimation of the area stained for fibronectin, phosphorylase and alizarin red S was performed and evaluated statistically. Phosphorylase, periodic acid-Schiff, fibronectin and alizarin red S allowed delineation of affected myocardium after 30 min of ischaemia followed by reperfusion whereas with the other stains, affected myocardium was readily detectable only after 60 or 90 min of ischaemia followed by reperfusion as well as after 24 h of ischaemia without reperfusion. The immunostaining for fibronectin was very distinct and inversely related to the phosphorylase activity. We show that fibronectin is an excellent marker for damaged cells and that these positively stained myocytes are necrotic as confirmed ultrastructurally. Using alizarin red S as a marker of calcium accumulation in myocytes, a marked discrepancy was observed between the area of fibronectin-containing myocytes and that of myocytes stained by alizarin red S. Calcium accumulation in mitochondria is thus not a prerequisite for myocyte necrosis but does occur only in some of the irreversibly damaged cells. Of special interest is the finding that there was a significant reduction of intracellular calcium in pigs where superoxide dismutase had been used as an adjunct at reperfusion, thus supporting the theory that free radicals do play a role during reperfusion of ischaemic myocardium. PMID- 1284061 TI - T-cell receptor beta usage by 35 different antigen-specific T-cell clones restricted by HLA-Dw4 or -Dw14.1. AB - We studied whether antigen-specific T cells being restricted by the very similar HLA-Dw4 and/or -Dw14.1 molecules might demonstrate homogeneities in parts of their TCR. TCCs were generated from three individuals who were all HLA-Dw4/Dw14.1 heterozygous. Thirty-five TCCs specific for PPD or TT and restricted by HLA-Dw4 and/or -Dw14.1 were selected for TCR beta gene sequencing. We found that 19 different V beta genes from 13 V beta families were expressed by these TCCs. Thus, it seems that many different TCRV beta genes may be used by TCCs restricted by these HLA molecules. For PPD-specific TCCs, a possible biased usage of V beta 8, as well as possible preferential usage of a CDR3 motif, were found. PMID- 1284062 TI - Cytomegalovirus- and interferon-related effects on human endothelial cells. Cytomegalovirus infection reduces upregulation of HLA class II antigen expression after treatment with interferon-gamma. AB - Cultured human umbilical vein endothelial cells (HUVEs) were infected with human cytomegalovirus (HCMV) strain AD169. Up to 50% HUVEs proved to be positive for HCMV early nuclear antigens 24 hours after inoculation with virus. Following infection kinetics of surface expression of HLA class I and II, intercellular adhesion molecule (ICAM-1) and endothelial lymphocyte adhesion molecule (ELAM-1) on HUVEs were investigated by means of flow cytometry. A slight increase in HLA class I expression was observed, whereas expression of HLA class II (DR, DP, DQ) antigens was not induced by infection with HCMV. Furthermore, when compared with uninfected cells treated with interferon-gamma (IFN-gamma), reduced enhancement of HLA-DR expression was conspicuous in HCMV-infected cells treated with IFN gamma. There is evidence that only a portion of HUVE is affected in its ability to upregulate HLA class II antigens. While expression of ICAM-1 was found to be enhanced between 8 and 20 hours after infection with a maximum at 12 hours after infection, no modulation of ELAM-1 was seen. PMID- 1284063 TI - Sperm surface proteins after capacitation. Expression of vitronectin on the spermatozoan head and laminin on the sperm tail. AB - Several integrins recognize as ligands proteins containing the Arg-Gly-Asp (RGD) sequence, such as fibronectin, vitronectin, and laminin. It has been previously demonstrated that oligopeptides containing the RGD sequence competitively inhibit both the adhesion of hamster and human sperm to zona-free hamster eggs and their subsequent penetration. In addition, the appearance of fibronectin on the surface of living human spermatozoa after capacitation has been demonstrated. In this work, it is shown that spermatozoa incubated overnight under capacitating conditions, but not fresh spermatozoa, also display the RGD-containing proteins vitronectin and laminin. Whereas the expression of fibronectin does not appear to be localized to any specific region of the sperm surface, laminin is present solely on the sperm tail, and vitronectin was detected mostly as an equatorial band on the sperm head. The percent of capacitated spermatozoa within each ejaculate reacting with antivitronectin antibodies (51% to 94%) was similar to that observed with antifibronectin antibodies (72% to 100%) in a series of fertile donors, and in a series of infertile men (7% to 98% for vitronectin versus 5% to 100% for fibronectin). In contrast, the percent of spermatozoa displaying laminin was lower, ranging from 2% to 42% for fertile donors and from 5% to 34% for infertile donors, and was unrelated to the expression of fibronectin or vitronectin. The time of appearance of both fibronectin and vitronectin when spermatozoa were incubated under capacitating conditions varied for different sperm donors, suggesting a difference in the process of their expression between different men. The specificity of antivitronectin antibody binding to human spermatozoa was demonstrated by competitive inhibition with purified human vitronectin. That there was no immunologic reaction between the antivitronectin antibodies used and fibronectin was demonstrated both by the failure of free fibronectin to inhibit antivitronectin antibody binding to spermatozoa, and by Dot blot analysis. A partial cross-reaction of the polyclonal antivitronectin antibody with fibronectin was shown by Western blot analysis, but this phenomenon was not present when the monoclonal antivitronectin antibody was used. In addition, both fibronectin and vitronectin could be extracted from capacitated spermatozoa solubilized in Chaps buffer, as shown by Dot blot and Western blot analysis. These observations suggest that vitronectin and fibronectin expressed on the surface of capacitated human spermatozoa could act as a ligand for specific receptors on the egg, and play a role in sperm-oolemmal adhesion. PMID- 1284064 TI - Clinical application of epidermal growth factor in ocular surface disorders. PMID- 1284065 TI - Cytokine mapping in human keratinocytes and keratinocyte cell line by reverse transcriptase-polymerase chain reaction (RT-PCR) method. PMID- 1284066 TI - Proteins of the cornified envelope. AB - The cornified envelope of keratinocytes is an insoluble structure formed beneath the plasma membrane at the base of the stratum corneum. It is made by cross linking precursor proteins by a membrane-associated transglutaminase. Using the cornified envelope of cultured human keratinocytes as the immunogen, we obtained a number of monoclonal antibodies which stained epidermis in a variety of ways. The peripheral staining pattern has been associated with several envelope precursors and this has been confirmed by western blots. A mouse IgM monoclonal antibody directed against epidermal basal cell hemidesmosomes was also discovered. By immunofluorescence, the monoclonal antibody produced a strong linear staining of the basement membrane zone and a polar cap on trypsin dissociated epidermal basal cells. By immunoelectron microscopy, immunoreactants were present in the attachment plaques of hemidesmosomes on guinea pig esophagus. However, no protein reactive with the antibody was detected. This study suggests that an antigen associated with the basal cell hemidesmosomes may be incorporated in the cornified envelope. PMID- 1284067 TI - Keratohyalin, trichohyalin and keratohyalin-trichohyalin hybrid granules: an overview. AB - Filaggrin and trichohyalin are the two major intermediate filament associated proteins which interact with keratin filaments in the skin. These two proteins initially accumulate in cytoplasmic granules called keratohyalin or trichohyalin granules which provide prominent morphological hallmarks of differentiation in the epidermis and the inner root sheath of hair follicles, respectively. The contents of each of these granules are modified and subsequently released into the cytoplasm of the fully mature cells where they function in the role of aggregating keratin filament bundles. We are beginning to identify several important aspects relative to the unique biological functions of both filaggrin and trichohyalin during the late stages of keratinocyte differentiation. This overview summarizes recent work on these proteins and will also highlight the existence of novel cytoplasmic granules, keratohyalin-trichohyalin hybrid granules, in dorsal tongue epithelia. PMID- 1284068 TI - Cystatin alpha is one of the component proteins of keratohyalin granules. PMID- 1284069 TI - Control of the distribution of hemidesmosome components in cultured keratinocytes: Ca2+ and phorbol esters. AB - DJM-1 cells (a human squamous cell carcinoma cell line) grown in low Ca2+ medium did not form cell-cell junctions of desmosome-keratin intermediate filament (KIF). When they were shifted to normal (high) Ca2+ medium, rapid translocation of desmoplakins from the cytosol to the plasma membrane to form desmosomes and reorganization of 180 kd-hemidesmosome proteins were induced almost simultaneously. In correlation with these morphological responses, the Ca2+ shift caused a breakdown of inositol phospholipids, a formation of diacylglycerol (DAG) and inositol trisphosphate (IP3), protein kinase C (PKC) activation, and Ca2+ influx. 12-0-tetradecanoylphorbol-13-acetate (TPA)-treatment of low Ca(2+)-grown DJM-1 cells also caused desmosome formation in association with PKC activation. These TPA effects were cancelled with PKC inhibitors, 1-(5-isoquinolinylsulfomyl) 2-methylpiperazine (H7) and staurosporine. Treatment with other PKC-activating agents, phorbol-12,13-butyrate (PDBu) and diaoctanoylglycerol (DOG), also induced desmosome formation. TPA-treatment of normal Ca(2+)-grown cells collapsed the organized distribution of the 180 kd-hemidesmosome protein and appeared to detach this protein from the cell-matrix adhering sites. This effect was also inhibited by H7. These results suggest that PKC activation plays important roles in upregulation of cell-cell junctions and downregulation of cell-matrix junctions in association with differentiation of keratinocytes. PMID- 1284070 TI - Regulation of epidermal keratin expression by retinoic acid and thyroid hormone. AB - In the epidermis, retinoic acid (RA) is known to regulate the gene expression of keratins, the intermediate filament proteins of epithelial cells. We have cloned the upstream regulatory regions of three human epidermal keratin genes, K5, K10, and K14, and engineered DNA constructs in which these regions drive expression of the CAT reporter gene. By co-transfecting the constructs into various epithelial cell types along with the vectors expressing the nuclear receptors for RA and thyroid hormone (T3), we have shown that RA and T3 directly regulate expression of these three keratin genes through the action of their nuclear receptors. In this paper, we review our previous results to stress that RA has a dual effect on keratin expression in epidermis: both direct and indirect. We also analyze the DNA sequences upstream from those three RA-regulated keratin genes and identify the clusters of degenerate consensus half-site motifs, which may comprise the putative retinoic acid recognition elements (RAREs). Furthermore, our recent results concerning the regulation of K5 and K14 expression by the RA receptor are also shown; these confirm our predictions regarding the location of the RAREs in epidermal keratin genes. PMID- 1284071 TI - Evidence of differentiated keratin peptide (K1) in cultured human squamous cell carcinomas: demonstration of generality by three different approaches. AB - The largest keratin peptide (K1, 68KD) has not been detectable in cultured human squamous cell carcinomas. However, quite recently, the K1 peptide was clarified to be present in two kinds of cultured HSC by using a low salt aqueous solution, rather than the high salt and Triton X-100 employed by many previous researchers (Biochem. Biophys. Res. Commun., 182, 1440-1445, 1992). To determine whether this phenomenon is common or not in cultured HSCs, I further demonstrated the K1 peptide by extracting it with two different buffers and by 2D-PAGE, immunological techniques, and Northern blot analysis, using another kind of HSC. Until now, keratin extraction has been done using high salt/Triton X-100 solution, during which K1 peptide may be removed because it has developed an affinity with the buffer. Many investigators may have therefore overlooked it. PMID- 1284072 TI - Inactivation of keratin genes by gene targeting: a perspective. AB - Recent technological advances in experimental molecular genetics have provided an opportunity for determining the function of any gene including those which are important in different epithelia. This report summarizes some recent results of experiments utilizing gene targeting technology to determine the function of intermediate filaments and emphasizes both the problems and the potential of applying this technology to problems in dermatology. PMID- 1284073 TI - In vitro keratin expression of hair cells. AB - Human hair follicles were isolated from the scalp by dispase and collagenase treatment and dispersed into a cell suspension by trypsin. These cells proliferated well and could be subcultured 7 to 8 times. The medium used was MCDB 153 HAA medium further supplemented with some amino acids, hydrocortisone, insulin, EGF, and bovine brain extract. The concentration of Ca++ was adjusted to 0.1 mM. Immunohistochemically, these cells were proved to possess keratins specific to hair forming cells. PMID- 1284074 TI - Dysregulated expression of cellular adhesion molecules in autoimmune-prone mice. AB - The expression of various cell adhesion molecules on lymphocytes and endothelial cells was examined. The strong expression of CD44 antigen on abnormal double negative T cells of lymph nodes was characteristic in MRL-lpr mice. The accumulation of abnormal double negative T cells in swelling lymph nodes was also predominant in MRL-lpr mice; this may result from augmented binding of lymphocytes to endothelial cell surfaces of lymph nodes, possibly due to the failure of Mel-14 antigen shedding from abnormal lymphocyte cell surface. The expression of VCAM-1 antigen was detected in endothelial cell surface of lymph nodes in MRL-lpr mice, which also explains the accumulation of lymphocytes in lymph nodes. However, the expression of VLA-4 antigen on lymphocytes which interact with VCAM-1 on endothelial cells was not significantly different between MRL-lpr and MRL(-)+ mice. PMID- 1284075 TI - Analysis of expression and soluble form of intercellular adhesion molecule-1 in malignant melanoma. AB - The effects of interferon (IFN) on the expression of ICAM-1 in human melanoma cell lines and the shedding of ICAM-1 into spent media were investigated using an indirect binding assay and a double determinant immunoassay (DDIA). While IFN increased the level of expression of ICAM-1 on melanoma cell lines, the susceptibility to IFN differed according to cell line. The enhancing effect of IFN-gamma was concentration-dependent, and it exceeded those of IFN-alpha and IFN beta. Shedding of ICAM-1 into spent media was detected effectively, and the results agreed well with the expression of ICAM-1 on melanoma cells. Immunostaining of the surgically removed melanoma lesions was positively correlated with the thickness of the primary lesion. The expression of ICAM-1 in primary melanoma lesions was inversely correlated with the disease-free interval. The circulating ICAM-1 with stage 4 melanoma patients significantly exceeded that of stage 1-3 melanoma patients. These observations suggest that ICAM-1 in its soluble form may play an important role in host immunities and may be useful in evaluating the prognosis of patients with melanoma. PMID- 1284076 TI - Transitory elevation of serum amylase levels after restorative proctocolectomy. AB - The incidence of postoperative hyperamylasaemia was evaluated in 70 patients who underwent staged restorative proctocolectomy. On the 14th postoperative day, 27 of 70 patients after total colectomy showed hyperamylasaemia, and the serum amylase returned to normal on the 30th postoperative day. Three out of 37 after ileoanal anastomosis and 8 out of 70 after stoma closure showed elevation of serum amylase postoperatively. Total colectomy might have a possible role in the postoperative increase of serum amylase. None of these patients had any obvious clinical evidence of postoperative pancreatitis. In 7 patients showing significant elevation of serum amylase levels (over 1000 IU), this was due predominantly to the pancreatic isoenzyme. This transitory elevation of serum amylase did not seem to be altered by the administration of therapeutic agents for pancreatitis. These observations suggest that postoperative hyperamylasaemia without clinical evidence of pancreatitis is very common after total colectomy, and that postoperative hyperamylasaemia itself does not necessarily require treatment. PMID- 1284077 TI - Ionic mechanisms of transient inward current in the absence of Na(+)-Ca2+ exchange in rabbit cardiac Purkinje fibres. AB - 1. Membrane currents were measured with a two-microelectrode technique in voltage clamped rabbit cardiac Purkinje fibres under conditions known to cause intracellular calcium overload and to eliminate or minimize Na(+)-Ca2+ exchange. 2. Increasing [Ca2+]o from 2.5 to 5 mM or above and substituting external sodium with either sucrose, choline or Li+ induced an oscillatory transient inward current (TI) which peaked 200-300 ms after repolarization from a previous depolarizing pulse. The TI quickly disappeared upon return to normal Tyrode solution. Both the rate and configuration of action potentials of Purkinje fibres also returned to control upon return to Tyrode solution after 30 min of high Ca2+ exposure, if the Ca2+ concentration was 30 mM or less. 3. The TI in Na(+)-free solution was Ca2+ dependent. Either zero or low (2.5 mM) [Ca2+]o, or replacement of [Ca2+]o by BaCl prevented induction of the TI current upon repolarization from a previous depolarizing pulse. 4. In the presence of 30 mM-CaCl2 and with choline chloride as the substitute for NaCl, TI had a distinct reversal potential (Erev) of -25 mV. The time-to-peak TI, either inward or outward, did not shift significantly with change in voltage. Both inward and outward TI were simultaneously abolished by exposure to 1 microM-ryanodine, suggesting they were both activated by transient release of Ca2+ from the sarcoplasmic reticulum. The occurrence of TI in the absence of [Na+]o is not compatible with an electrogenic Na(+)-Ca2+ exchange mechanism. The existence of a clear-cut reversal potential suggests that an ionic channel may be responsible for the TI under these conditions. 5. Both the magnitude of peak TI and the Erev were affected by changes of CaCl2 concentration. (i) Under steady-state conditions, peak inward TI was significantly increased when the [Ca2+]o was elevated from 5 to 15 mM. The peak TI in the outward direction was significantly increased when [Ca2+]o was elevated from 15 to 30 mM; however, the difference in peak inward TI at 15 and 30 mM [Ca2+]o was small. (ii) Clear-cut reversals of TI were found at Ca2+ concentrations of 10 mM (Erev = -19.5 mV) or greater, and elevation of [Ca2+]o to 20, 30, 50 and 105 mM shifted the Erev to more negative potentials. (iii) In the presence of 5 mM [Ca2+]o the inward TI declined to zero at about -30 mV, and test voltages between -55 and +5 mV failed to reveal a distinct outward TI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284078 TI - Stretch-activated anion currents of rabbit cardiac myocytes. AB - 1. Stretch-activated anion currents were studied in sino-atrial and atrial cells using the whole-cell patch clamp technique. With continuous application of positive pressure (5-15 cmH2O) through the patch clamp electrode, the cell was inflated and the membrane conductance was increased. 2. Voltage clamp steps revealed that the stretch-activated currents had time-independent characteristics. The increase in membrane conductance was reversible on subsequent application of negative pressure to the electrode. 3. The reversal potential of the stretch-activated currents was shifted by 60 mV for a 10-fold change in intracellular Cl- concentration, while it was unaffected by replacement of Na+ in the extracellular solution by N-methyl-D-glucamine. Cell superfusion with Cl(-)-deficient solution (10 mM Cl-) reduced the amplitude of outward current. These findings indicate that the stretch-activated conductance is Cl- selective. 4. The sequence of anion permeability through the stretch-activated conductance was determined to be I-(1.7) > NO3-(1.5) > Br-(1.2) > Cl-(1.0) > and F-(0.6). SCN- appeared to be more permeant than I-. 5. The stretch-activated conductance was reduced by the Cl- channel blockers, 4,4'-dinitrostilbene-2,2' disulphonic acid disodium salt, 4-acetamido-4'-isothiocyanatostilbene-2,2' disulphonic acid or anthracene-9-carboxylate (9-AC). Administration of furosemide or bumetanide had no effect. 6. The stretch-activated Cl- current was recorded even though intracellular Ca2+ ions were chelated by including 10 mM EGTA in the pipette solution. Neither the specific peptide inhibitor of cyclic AMP-dependent protein kinase (50 microM), nor the non-selective blocker of protein kinases, H-7 (20 microM), was effective in reducing the stretch-activated Cl- current, suggesting that the stretch-activated Cl- current is a novel type of cardiac Cl- current, which shows a different modulatory mechanism from that of other cardiac Cl- currents. PMID- 1284079 TI - Volume-regulatory Cl- channel currents in cultured human epithelial cells. AB - 1. During osmotic swelling, cultured human small intestinal epithelial cells (Intestine 407) exhibited activation of large Cl- currents under the patch-clamp whole-cell configuration. The volume-sensitive Cl- conductance was independent of intracellular Ca2+ and cyclic AMP. 2. The anion permeability sequence of the current was SCN- > I- > Br- > Cl- > F- > gluconate-, corresponding to Eisenman's sequence I. 3. Cl- currents were instantaneously activated by command pulses in a range of -120 to +45 mV. At potentials more positive than +50 mV the current showed a time-dependent inactivation. This inactivation was accelerated by increased depolarization. The instantaneous current-voltage relationship rectified in the outward direction. 4. A stilbene-derivative Cl- channel blocker, 4-acetamido-4'-isothiocyanostilbene (SITS), inhibited the Cl- current at micromolar concentrations. SITS facilitated inactivation at positive potentials. Outward currents were more prominently suppressed by SITS than inward currents. The concentrations required for 50% inhibition (IC50) of outward and inward currents were 1.5 and 6 microM, respectively. The outward and inward currents were equally inhibited by a carboxylate analogue Cl- channel blocker, 5-nitro-2 (3-phenylpropylamino)-benzoate (NPPB) or diphenylamine-2-carboxylate (DPC) at higher doses (IC50 = 25 for NPPB or 350 microM for DPC). Inactivation kinetics at large depolarizations was not affected by NPPB or DPC. 5. The Cl- current was blocked by an unsaturated fatty acid, arachidonic acid (IC50 = 8 microM). Arachidonic acid was still effective in the presence of inhibitors of lipoxygenase (nordihydroguaiaretic acid, 10 microM), cyclo-oxygenase (indomethacin, 10 microM) and protein kinase C (polymyxin B, 30 microM). The Cl- current was also sensitive to another cis unsaturated fatty acid, oleic acid, which is not a substrate for oxygenases. A trans isomer of oleate, elaidic acid, and a saturated fatty acid, palmitic acid, were ineffective. 6. Single Intestine 407 cells exposed to a hypotonic solution showed a regulatory volume decrease after initial osmotic swelling. The volume regulation was abolished by SITS, NPPB, arachidonate and oleate, but not by elaidate and palmitate. 7. It is concluded that outwardly rectifying Cl- channels, which are sensitive to arachidonic acid, are activated upon osmotic swelling and involved in the subsequent cell volume regulation. PMID- 1284080 TI - Resting membrane potential and potassium currents in cultured parasympathetic neurones from rat intracardiac ganglia. AB - 1. Whole-cell K+ currents contributing to the resting membrane potential and repolarization of the action potential were studied in voltage-clamped parasympathetic neurones dissociated from neonatal rat intracardiac ganglia and maintained in tissue culture. 2. Rat intracardiac neurones had a mean resting membrane potential of -52 mV and mean input resistance of 850 M omega. The current-voltage relationship recorded during slow voltage ramps indicated the presence of both leakage and voltage-dependent currents. The contribution of Na+, K+ and Cl- to the resting membrane potential was examined and relative ionic permeabilities PNa/PK = 0.12 and PCl/PK < 0.001 were calculated using the Goldman Hodgkin-Katz voltage equation. Bath application of the potassium channel blockers, tetraethylammonium ions (TEA; 1 mM) or Ba2+ (1 mM) depolarized the neurone by approximately 10 mV. Inhibition of the Na(+)-K+ pump by exposure to K(+)-free medium or by the addition of 0.1 mM ouabain to the bath solution depolarized the neurone by 3-5 mV. 3. In most neurones, depolarizing current pulses (0.5-1 s duration) elicited a single action potential of 85-100 mV, followed by an after-hyperpolarization of 200-500 ms. In 10-15% of the neurones, sustained current injection produced repetitive firing at maximal frequency of 5 8 Hz. 4. Tetrodotoxin (TTX; 300 nM) reduced, but failed to abolish, the action potential. The magnitude and duration of the TTX-insensitive action potential increased with the extracellular Ca2+ concentration, and was inhibited by bath application of 0.1 mM Cd2+. The repolarization rate of the TTX-insensitive action potential was reduced, and after-hyperpolarization was replaced by after depolarization upon substitution of internal K+ by Cs+. The after hyperpolarization of the action potential was reduced by bath application of Cd2+ (0.1 mM) and abolished by the addition of Cd2+ and TEA (10 mM). 5. Depolarization activated outward K+ currents were isolated by adding 300 nM TTX and 0.1 mM Cd2+ to the external solution. The outward currents evoked by step depolarizations increased to a steady-state plateau which was maintained for > 5 s. The instantaneous current-voltage relationship, examined under varying external K+ concentrations, was linear, and the reversal (zero current) potential shifted in accordance with that predicted by the Nernst equation for a K(+)-selective electrode. The shift in reversal potential of the tail currents as a function of the extracellular K+ concentration gave a relative permeability, PNa/PK = 0.02 for the delayed outward K+ channel(s).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284081 TI - Intracellular cations modulate noradrenaline-stimulated calcium entry into smooth muscle cells of rat portal vein. AB - 1. The action of noradrenaline (NA, 10 microM) was studied in single patch clamped smooth muscle cells of rat portal vein where free internal Ca2+ concentration in the cell (Ca2+i) was estimated using the emission from the dye Indo-1. 2. In the presence of 50 microM D600, a blocker of voltage-dependent Ca2+ channels, NA applied to the cell evoked an initial peak in Ca2+i followed by a smaller sustained rise. The initial rise in Ca2+i was associated with the activation of Ca(2+)-dependent Cl- channels. 3. The maintained rise in Ca2+i induced by NA was enhanced by increasing the external Ca2+ concentration and was abolished in Ca(2+)-free solution. The transient rise was resistant to the absence of external Ca2+. 4. Following the transient rise in Ca2+i induced by NA, the mechanisms extruding and/or sequestering cytoplasmic Ca2+ were stimulated. This stimulation was measured during the sustained rise in Cai and was maintained for a few seconds after NA was removed. 5. Unlike the transient rise in Ca2+i, the sustained rise in Ca2+i produced by NA was affected by changing the cell membrane potential. 6. Changing the Na+ gradient showed that the Na(+)-Ca2+ exchange was not involved in the sustained rise in Ca2+i. 7. The sustained increase in Ca2+i produced by NA was modulated by intracellular cations. This phase could be observed with 130 mM Na+ or 130 mM K+ in the pipette solution, but was severely reduced when the only cation in the intracellular solution was Cs+ and abolished with NMDG (N-methyl-D-glucamine) or TEA. However, inclusion of only 10 mM Na+ or 50 mM K+ in the pipette solution was sufficient to obtain a sustained rise in Ca2+i of maximal amplitude, similar to that obtained with 130 mM Na+i or 130 mM K+i during NA application. 8. In portal vein smooth muscle cells, NA induced a two-phase increase in Ca2+i similar to the two phases which have been previously observed upon muscarinic receptor activation by carbachol in intestinal smooth muscle. The transient rise was due to Ca2+ store release whereas the sustained rise was due to an increased Ca2+ entry into the cell down its electrochemical gradient, but not through voltage-dependent Ca2+ channels. The Ca2+ permeability pathway involved in the sustained rise in Ca2+i induced by NA was modulated by the intracellular cations. PMID- 1284082 TI - The antiatherogenic effects of amlodipine: promise of preclinical data. AB - Atherosclerosis is a complex and multifactorial disease, the endpoint of which is the formation of a calcified plaque. Intermediate events include intimal injury, smooth muscle cell proliferation and migration, macrophage infiltration, lipid accumulation and excess formation of ground substance. To determine whether the newly developed, long-acting calcium antagonist, amlodipine, slows the development of atherosclerotic lesions under experimental conditions, young New Zealand white rabbits were fed on a diet of 2% cholesterol plus 1% peanut oil for up to 12 weeks. Half the rabbits received 1 or 5 mg amlodipine/kg body weight/day. Amlodipine caused a significant and dose-dependent reduction in lesion formation in the thoracic aorta. At the same time thoracic aorta Ca2+ and cholesterol content were maintained at near normal levels, despite the raised plasma cholesterol levels. The protective effect of amlodipine persisted throughout a treatment period of 12 weeks, indicating the absence of tachyphylaxis. PMID- 1284083 TI - Effects of niacin on bleomycin-induced increases in myeloperoxidase, prolyl hydroxylase, and superoxide dismutase activities and collagen accumulation in the lungs of hamsters. AB - It has been shown that lung nicotinamide adenine dinucleotide (NAD) depletion accompanies bleomycin (BL)-induced lung fibrosis in the hamster and that treatment with niacin (NA), a precursor of NAD, was found to attenuate lung fibrosis caused by this agent. Niacin was used in the present study to investigate changes in some biochemical parameters and enzymes involved in the development of BL-induced lung fibrosis in the hamster. Niacin (500 mg/kg, IP), or an equivalent volume of saline (SA, IP), was given daily 2 days prior to intratracheal instillation of BL (7.5 U/5 mL/kg) or SA and everyday thereafter throughout the study. Hamsters were killed at 1, 4, 7, 10, and 14 days after the BL or SA instillation and their lungs processed for various biochemical assays. Hydroxyproline content and superoxide dismutase (SOD) activity in SABL treated animals were significantly (P < or = 0.05) elevated at 7 and 10 days, peaking at 14 days to 161 +/- 11% and 159 +/- 11% of the SASA treated animals, respectively. Although the hydroxyproline level of NABL treated animals was significantly elevated at 7 and 10 days and peaked at 14 days to 123 +/- 8% of the NASA control, these values were significantly lower than the SABL treated animals at the corresponding times. The lung SOD activity of NABL groups was significantly higher at 4 days but significantly lower at 10 and 14 days than the SABL groups at the corresponding times. Prolyl hydroxylase (PH) activity and total lung calcium in SABL treated groups were significantly elevated compared to SASA treated groups starting at 4 days, with PH peaking at 10 days to 163 +/- 13% and calcium peaking at 7 days to 148 +/- 8% of SASA treated groups. The NABL treated animals displayed a significant elevation in PH activity at 4 days only (132 +/- 15%), while the calcium content in this group was significantly increased at 4 and 14 days compared to NASA treated animals. However, the activity of PH in the NABL treated animals was significantly lower than the SABL treated animals at 7, 10, and 14 days. The calcium content of the NABL group was significantly lower than the SABL group at 7 and 10 days. The thiobarbituric acid reactive substance equivalents (TBARS) content and myeloperoxidase (MPO) activity were significantly elevated at all time points in SABL groups as compared to SASA groups, with peak elevation of TBARS to 160 +/- 9% at 4 days and MPO to 268 +/- 40% at 1 day.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284084 TI - Tryptophan and serotonin metabolism in familial erythrophagocytic lymphohistiocytosis. AB - Reduced concentrations of tryptophan and 5-hydroxyindoleacetic acid (the major CSF metabolite of serotonin) were found in the cerebrospinal fluid of two children with familial erythrophagocytic lymphohistiocytosis. This was associated with elevated cerebrospinal fluid neopterin concentrations indicating increased macrophage activity within the central nervous system. In one child, cytotoxic therapy induced a complete clinical remission and an increase of tryptophan and 5 hydroxyindoleacetic acid concentrations to normal; during a subsequent relapse, concentrations of these analytes again fell below normal. In the other child, in whom therapy produced only a transient improvement, tryptophan and 5 hydroxyindoleacetic acid concentrations remained low and the child died. It is likely that increased activity of indoleamine 2,3-dioxygenase induced by the activation of macrophages was responsible for the disturbance in serotonin and tryptophan homeostasis within the brain. Excessive tryptophan catabolism and the disturbance of serotonin turnover may play a role in the aetiology of the neurological symptoms seen in familial erythrophagocytic lymphohistiocytosis. PMID- 1284085 TI - Immune proteins in peripheral tissue fluid-lymph in patients with filarial lymphedema of the lower limbs. AB - Immune proteins and cytokine concentrations and activity were measured in skin tissue fluid-lymph and blood serum of patients with lower leg filarial lymphedema. High levels of lymph gamma-globulins, alpha-1-acid glycoprotein and IgG lymph/serum ratio were found. Lymph from filarial patients had an elevated lymph stimulatory effect on blood mononuclear cell culture with phytohemagglutinin. There was also a high concentration and activity of IL-1 beta but gamma-interferon was not detected. The deranged pattern of immune proteins and high activity of IL-1 suggest persistence of an ongoing local inflammatory process despite the absence of overt dermatitis. The high tissue-lymph IL-1 concentration and activity may signify a cytokine network promoting keratinocyte and fibroblast proliferation commonly seen on skin histology in patients with filariasis. PMID- 1284086 TI - Ventricular beat classifier using fractal number clustering. AB - A two-stage ventricular beat 'associative' classification procedure is described. The first stage separates typical beats from extrasystoles on the basis of area and polarity rules. At the second stage, the extrasystoles are classified in self organised cluster formations of adjacent shape parameter values. This approach avoids the use of threshold values for discrimination between ectopic beats of different shapes, which could be critical in borderline cases. A pattern shape feature conventionally called a 'fractal number', in combination with a polarity attribute, was found to be a good criterion for waveform evaluation. An additional advantage of this pattern classification method is its good computational efficiency, which affords the opportunity to implement it in real time systems. PMID- 1284087 TI - [The effect of occupational environment on the development of skin lesions in workers at a tableware porcelain plant]. AB - This work reports on the skin diseases which occur among the workers of the ceramic industry. The most frequently observed diseases were: dermatomycosis, eczema as a result of wear, and allergic diseases. Nickel, and also cobalt, turpentine, paraphenyldiamine and detergents were the main allergens. Mycotic infection was observed primarily among the workers using common bathrooms. PMID- 1284088 TI - [The isolation of ribosomes from Acholeplasma and the study of their physicochemical characteristics]. AB - Ribosomes are produced from Acholeplasma laidlawii PG-8 and A. laidlawii var. granulum str. 118. It is proved as possible to use the standard method of differential centrifugation for isolation of mollicute ribosomes. The physico chemical properties of acholesplasma ribosomes are studied. The protein content for A. laidlawii PG-8 amounted to 39.6%, rRNA content--60.4% and for A. laidlawii var. granulum--39.1 and 60.8%, respectively. The RNA: protein ratio equals 1.5:1, the ratio of optic density indicates at 260 and 280 nm--2, that is peculiar to treated preparations of ribosomes. Sedimentation coefficient of acholeplasma ribosomes is 70S. The produced preparations of acholeplasma ribosomes can be used subsequently for creating the system of translation in vitro to study the biosynthesis processes of mollicute protein. PMID- 1284089 TI - [The agglutinability of cholera O-monoclonal immunoglobulins]. AB - A set of 10 monoclonal antibodies specific for vibrio species and of 5 monoclonal antibodies specific for serovar (Ogawa) was studied. These monoclonal antibodies were directed toward V. cholerae O1 antigen in agglutination reaction and on slide plates. Monoclonal antibodies agglutinating typical strains of cholera vibrios with titration range from 1: 6000 to 1: 25,000 were selected. MA were revealed to interact with cholera vibrio strains with reduced agglutinability. The set of agglutinating O monoclonal immunoglobulins was developed for laboratory identification of cholera O1 vibrios. PMID- 1284090 TI - [The effect of the acid exopolysaccharide produced by the causative agent of melioidosis on macrophage function]. AB - Acid exopolysaccharide of the melioidosis agent, isolated from the slime of alysogenic strain of Pseudomonas pseudomallei SVBDO-141 inhibits the capture of sheep erythrocytes--55Fe by mouse peritoneal macrophages. Administration of the sheep erythrocytes--55Fe, sensibilized by acid exopolysaccharide was proved not to have an antiphagocytic effect. Inhibition of phagocytic macrophagal activity depends on the conditions of isolation of acid exopolysaccharide. PMID- 1284091 TI - Structure and function of inhibitory glycine receptors. PMID- 1284092 TI - Theoretical perspectives on ion-channel electrostatics: continuum and microscopic approaches. PMID- 1284093 TI - [Plasma histamine levels after the administration of atracurium or pancuronium in patients undergoing general anesthesia]. AB - OBJECTIVES: To compare the release of histamine induced by atracurium and pancuronium. MATERIAL AND METHODS: We studied 20 patients ASA III undergoing vascular surgery under etomidate anesthesia. Patients were randomly treated with either 0.5 mg/kg of atracurium or 0.1 mg/kg of pancuronium as muscle relaxant agents. Plasma histamine concentration, heart rate, arterial blood pressure, PaO2, and PaCO2 were measured at the basal state and 1.2 and 5 min after administration of the muscle relaxant drug. RESULTS: Plasma histamine concentration at baseline were 0.691 +/- 0.6 ng/ml in the atracurium group and 0.756 +/- 0.612 ng/ml in the pancuronium group. These levels raised up to 2.748 +/- 6.278 ng/ml (atracurium) and 2.553 +/- 5.454 ng/ml (pancuronium). These differences were not statistically significant. The course of the remaining parameters studied in these patients was also comparable between the two groups. There were no clinical manifestations associated with the release of histamine. CONCLUSIONS: Plasma levels of histamine after administration of atracurium were not significantly different from those induced by pancuronium. PMID- 1284094 TI - [The value of Neupogen in neutropenia]. PMID- 1284095 TI - Identification and characterization of a parasite antigen in the circulating immune complexes of Onchocerca volvulus infected patients. AB - A PEG-ELISA was used to demonstrate parasite specific immune complexes in a significant proportion (25/26) of Onchocerca volvulus infection sera from Sierra Leone. The parasite antigen was detected using a peroxidase-conjugated rabbit serum raised to the bovine parasite O. gibsoni. Controls including European control serum, endemic control serum and Rh+ sera gave consistently low readings. Characterization of the parasite component in the immune complexes by Western blotting demonstrated a heat stable antigen of M(r) 46,000. This antigen was not present in the circulating immune complexes (CIC) prepared from patients with Wuchereria bancrofti infection, but a cross-reactive molecule of the same size was weakly recognized in the CIC of Loa loa and Mansonella perstans infected patients. No association between the level of parasite specific CIC and clinical disease was observed in the O. volvulus patients. PMID- 1284096 TI - [Comparative sensitivity of different solid-phase immunoassays for detecting HBsAg and anti-HCV in blood]. AB - The sensitivities of seven methods of enzyme-immunoassay for HBsAg detection, as well as of twelve immunoassays for detecting antibody to HCV, were compared, in an attempt to evaluate the need for an official technical validation of such methods prior to its commercialization in Spain. Significant differences were seen for the sensitivities of these methods, which may influence the proficiency of blood bank screening for HBsAg and anti-HCV for preventing cases of post transfusional viral hepatitis. As a conclusion, it is recommended to establish legal regulations for pre-marketing validation of such assays in Spain, as well as to take the results obtained in these evaluation studies as the basis for selecting those tests which may be more convenient for screening purposes at the blood banks. PMID- 1284097 TI - [The first days following heart transplantation]. PMID- 1284098 TI - [A cytophotometric study of the RNA and glycogen content of human hepatocytes at different stages in the development of traumatic disease]. AB - Absorption and fluorescent cytophotometry techniques were applied to studies of RNA, glycogen and its fractions in hepatocytes of patients with hard mechanic trauma, both with and without endointoxication. For measuring RNA and glycogen contents, slides were stained by gallocyanin-chromalum or underwent fluorescent PAS-reaction, respectively. The repeated aspiration biopsy material was used for investigation of RNA and glycogen contents in dynamics. A quick increase in RNA content took place at the first stage (within the first 3 days) of traumatic illness of both the groups of patients. At the second stage of illness the hepatocyte RNA content in patients without endointoxication was seen to decrease to the initial level, whereas that in patients with endointoxication increased from the initial level by 36%. At different stages of illness the total glycogen content is changed insignificantly in the course of illness, but its labile fraction decreases to 70% of the total glycogen in patients with endointoxication. The increase of hepatocyte synthetic activity and the maintenance of the normal glycogen level may suggest a sufficient compensatory possibility of the liver, in spite of a high functional load under endointoxication. PMID- 1284099 TI - [The level of chromosomal DNA methylation in mice in the early stages of embryogenesis studied by the action of restriction endonucleases on the chromosomes]. AB - The degree of genome methylation was estimated on chromosomal slides of mouse zygotes, morulae and embryos of 10 day of gestation using in situ digestion with restriction endonucleases MspI and HpaII. The chromosome preparations of all the embryo stages were made by the same method. The degree of methylation was evaluated by the appearance of chromosomes after digestion and by staining with the Giemsa stain. At the zygote stage, both maternal and paternal genomes are more methylated than chromosomes of the next stages of development. The paternal genome is more methylated than maternal. The homologous chromosomes of morulae and 10 day embryos were identical and the pattern of G-banding was formed. PMID- 1284100 TI - Clinical chemistry profile data for Hispanics, 1982-84. AB - This report presents descriptive data for clinical chemistry profiles by age and sex. This information is from the Hispanic Health and Nutrition Examination Survey, a sample survey of selected groups of civilian noninstitutionalized Hispanic persons residing in the United States. The survey was conducted during 1982-84. PMID- 1284101 TI - RNA delivery in Saccharomyces cerevisiae using electroporation. AB - An efficient delivery method for introducing in vitro synthesized RNA into yeast has been developed using electroporation. Spheroplast preparation, electroporation, and subsequent expression analysis can be accomplished within a single day. The use of introduced mRNA constructs avoids any complications due to nuclear regulation and is particularly suited for cytoplasmic regulatory studies. Moreover, this technique is useful for introducing those RNAs that cannot be made in vivo, such as poly(A)- mRNAs or RNAs with base modifications. We demonstrate that the Escherichia coli GUS gene and the firefly Luc gene are both excellent reporter genes for RNA electroporation. PMID- 1284102 TI - High-performance capillary electrophoresis of SDS-protein complexes using UV transparent polymer networks. AB - This paper demonstrates the use of UV-transparent replaceable polymer networks for the separation of SDS-protein complexes on the basis of molecular weight. First, the use of linear (i.e. non-cross-linked) polyacrylamide is shown to provide molecular separation of SDS-protein complexes. A study reveals such columns to yield significantly greater lifetime than cross-linked gels because of the flexibility of the noncovalently attached polymer chains. However, column lifetime was still found to be limited (approximately 20-40 injections), and detection at 214 nm was problematical because of the absorbance of polyacrylamide. UV-transparent polymer networks of dextran and PEG were substituted for polyacrylamide with successful molecular weight sieving of SDS protein complexes at 214 nm. Due to their low to moderate viscosities, these networks could be routinely replaced leading to the possibility of hundreds of injections with a single column. Migration time reproducibilities of 0.5% RSD or less were found with replacement of the network. Using dextran, calibration plots of peak area vs concentration of standard protein were linear over the range of 0.5 microgram/mL up to at least 0.25 mg/mL. Furthermore, plasma samples could be directly utilized because of the strong solvating power of SDS. Rapid separation of protein mixtures are demonstrated with these UV-transparent polymer networks. PMID- 1284103 TI - Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis. AB - Levels of soluble IL-2 receptors, IL-6, soluble CD23, soluble CD14 and ECP (eosinophilic cationic protein) were measured as markers of T-cell, B-cell, monocyte and eosinophilic leucocyte activation in 26 patients with atopic dermatitis (AD) on admission to (A) and at discharge from (D) the Department of Dermatology in Zurich. The serum levels of sIL-2R, IL-6, sCD23, sCD14 and ECP were significantly elevated in AD patients in comparison with the normal values of healthy donors. A significant decrease in sIL-2R (p = 0.0093) and in sCD14 (p = 0.0134) levels was demonstrated between A and D, correlating with the improvement in the skin intensity score (SIS). In addition, a significant correlation of the sCD14 levels and the SIS at A was demonstrated (p = 0.0415). These results also incriminate monocytes in the pathogenesis of AD, indicating that, besides sIL-2R and ECP, SCD14 could also be a possible marker for the disease activity. PMID- 1284105 TI - [Transurethral thermotherapy in prostatic adenoma]. AB - Microwave thermotherapy is considered to be an alternative to conventional surgical treatment of benign prostatic hyperplasia (BPH). Our initial experience of the first six months shows this technique has achieved objective improvement of the symptoms and uroflowmetry, as well as a significant reduction of postmicturition residual urine. It carries a minimal morbidity, no mortality and has permitted recovery of micturition in over 90% of the patients with urinary retention. PMID- 1284104 TI - Epidermal growth in the skin equivalent. AB - The skin equivalent (SE) has been validated as a model for studies on proliferation of keratinocytes. SEs were prepared from normal skin by implanting punch biopsies on dermal equivalents consisting of fibroblasts in a collagen matrix. The outgrowths were measured by planimetry. An immunohistochemical investigation with antibodies against markers associated with proliferation was performed on frozen sections from SEs during outgrowth at 3-6 days (SE6) as well as after completion of outgrowth at 21 days (SE21). Biopsies from normal controls and from uninvolved and involved skin in psoriatic patients were also studied. The antibodies used were Ki-67, cytokeratin 8.12, and antibodies against the receptors for epidermal growth factor (EGFr) and transferrin (TFr). The increase in area was linear during the first 7 days of culture and usually reached the edges of the dermal equivalent at this time. In SE6 TFr was expressed in the basal part of the outgrowth while the other markers were not observed. In SE21 and in psoriasis there was abundant epidermal staining of Ki-67-positive nuclei and cytokeratin 8.12 was detected in the suprabasal part of the epidermis. EGFr and TFr were seen in the basal layer in SE21. In the psoriatic lesions these receptors were found both in the basal and suprabasal layers. The lack of proliferation markers in SE6 indicates that the initial increase in the area of keratinocytes is due to migration from the punch biopsies. Increased cell proliferation is present in SE21, a finding in common with psoriasis and wound healing. The skin equivalents should therefore be an appropriate model for studies on these phenomena. PMID- 1284106 TI - Congenital sensory neuropathy with anhidrosis (hereditary sensory neuropathy type IV). AB - Hereditary sensory neuropathies comprise a group of rare childhood diseases which are classified into four types. We present a Greek boy 11 years old with hereditary sensory neuropathy type IV (congenital sensory neuropathy with anhidrosis) whom we have followed up and studied during the last seven years. Our patient presented for the first time with recurrent hyperthermic episodes without sweating, and lack of pain sensation from the first months of life. Insensitivity to pain and thermal stimuli had resulted in burns on the extremities and self mutilation of the tongue, lips and fingertips. When he was five and seven years old respectively he had two painless fractures of the ankles which led to insoluble orthopedic problems. He also suffered from mental retardation, which was obvious from his first years of life. Sweat gland investigations showed significant hypohidrosis or anhidrosis although the sweat glands were normal microscopically. Hereditary sensory neuropathy type IV, although rare, is important for dermatologists because it must be differentiated from other anhidrotic syndromes, and in view of the poor prognosis of the condition. PMID- 1284107 TI - [Histochemical detection of hepatic iron. A comparative study of four stains]. AB - Due to its specificity and easiness, Perls' stain is widely used in the histochemical assessment of liver iron content. However, it can underestimate slight iron overload, which can hamper screening for genetic hemochromatosis, especially in young people. The aim for the present study was to compare Perls' stain to three other specific iron stains (Tirmann-Schmeltzer (TRM); Hukill and Putt (HPT); Perls with Diaminobenzidine (DAB)), biochemical liver iron concentration (LIC) being used as the reference. 1) There is a significant difference between number of stained cells with TRM or DAB, compare with Perls' stain (p < 0.05). 2) Correlation (r) between histological assessment (T) and LIC was 0.39 for Perls' stain, 0.64 for TRM 0.53 for HPT and 0.64 for DAB. These data suggest that Perls' stain is not the most sensitive method for the assessment of slight iron overload. Tirmann-Schmeltzer's stain and Perls plus dAB should be preferred, especially in the screening of early liver siderosis. PMID- 1284108 TI - [Problems in characterizing KL1, broad-spectrum anti-keratin antibody]. PMID- 1284109 TI - Modulation of gastric mucosal calcium channels activity by platelet-derived growth factor. AB - A dihydropyridine-sensitive gastric mucosal calcium channels were isolated from the solubilized epithelial cell membranes by affinity chromatography on wheat germ agglutinin. The channels following labeling the calcium antagonist receptor site with [3H]PN200-100 were reconstituted into phospholipid vesicles which exhibited active 45Ca2+ uptake as evidenced by La3+ displacement assays. The uptake of calcium was independent of sodium and potassium gradients indicating the electroneutral nature of the process. The channels responded in a dose dependent manner to dihydropyridine calcium antagonist, PN200-110, which at 0.5 microns exerted maximal inhibitory affect of 66% on 45Ca2+ uptake, while a 52% enhacement in 45Ca2+ uptake occurred with a specific calcium channel activator, BAY K8644. On platelet-derived growth factor (PDGF) binding in the presence of ATP, channel protein showed an increase in tyrosine phosphorylation of 55 and 170 kDa calcium channel proteins. Such phosphorylated channels following reconstitution into vesicles displayed a 78% greater 45Ca2+ uptake. The results demonstrate the importance of PDGF in the regulation of gastric mucosal calcium uptake. PMID- 1284110 TI - Identification of novel adhesion proteins in mouse peritoneal macrophages. AB - When mouse peritoneal macrophages were made to adhere firmly on glass surface and then removed by sequential treatment with hypotonic triethanolamine and Nonidet P 40, a set of proteins were found to be left behind at the sites of adherent cells. Such glass-adherent proteins were detected as round or ellipsoidal patches of autofluorescence under a confocal laser microscope, and visualized ultrastructurally as aggregates of narrow threads of unique loop structures which were composed of linearly aligned particles of 22 +/- 2 nm in diameter. Lithium dodecylsulfate-polyacrylamide gel electrophoresis of the glass-adherent proteins showed two major bands, 12 kDa and 14 kDa, which always co-existed in any different sample. The polyclonal antibody raised against these two proteins specifically stained the glass-adherent proteins in situ. The adhesion of macrophages to glass was significantly blocked with Fab fragments of the antibody. The in situ cross-linking experiment suggested that these two proteins might be closely associated with each other to form complexes. Hence, these proteins can be reasonably considered to be responsible for non-specific adhesion of macrophages to glass. PMID- 1284111 TI - Computer-assisted analysis of the structure of regular branched polysaccharides containing 2,3-disubstituted rhamnopyranose and mannopyranose residues on the basis of 13C NMR data. AB - A computer-assisted approach to the analysis of the structure of branched polysaccharides that contain 2,3-di-O-glycosylated alpha-rhamnopyranose and alpha mannopyranose residues is based on evaluation of the 13C NMR spectra, using glycosylation effects and their deviations from additivity (delta delta values) at the branch points. This approach, in combination with monosaccharide and methylation analysis data, has been verified on a series of bacterial polysaccharides of known structure. PMID- 1284112 TI - Structure of the O-antigen of Escherichia coli 0119 lipopolysaccharide. AB - The structure of the O-polysaccharide component of the lipopolysaccharide produced by Escherichia coli 0119 was determined by the use of methylation analysis, periodate oxidation, 1D and 2D nuclear magnetic resonance spectroscopy, and mass spectrometric methods. The O-polysaccharide was found to be a high molecular weight polymer of a repeating pentasaccharide unit composed of D mannose, D-galactose, L-rhamnose, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido 2,3-dideoxy-3-formamido-D-rhamnose residues (1:1:1:1:1) and had the structure: [formula: see text] PMID- 1284113 TI - Structures of the glycopeptidolipid antigens of serovars 25 and 26 of the Mycobacterium avium serocomplex, synthesis of allyl glycosides of the outer disaccharide units and serology of the derived neoglycoproteins. AB - The pentasaccharide hapten released from the glycopeptidolipid (GPL) antigen of M. avium serovar 26 has been characterized as O-(2,4-di-O-methyl-alpha-L fucopyranosyl)-(1-->4)- O-beta-D-glucopyranosyluronic acid-(1-->4)-O-(2-O-methyl alpha-L-fucopyranosyl)-(1-->3)-alpha-L- rhamnopyranosyl-(1-->2)-6-deoxy-L-talose. The allyl glycosides of the outer glycosyl and glycobiosyl units of this hapten have been synthesized, the latter by a route involving oxidation of the corresponding D-glucopyranose derivative. Conjugation of allyl glycosides to protein by ozonolysis and reductive coupling afforded neoantigens (neo 26-1 and 26-2), both of which interacted with antibodies to M. avium serovar 26. The terminal sugar residue of the pentasaccharide hapten of the serovar 25 GPL had been shown to have the galacto configuration on the basis of 1H-13C NMR correlation spectroscopy, but absolute configurational assignment for the sugar awaited the synthesis, as for neo 26, of two glycobiosyl NGPs bearing the terminal sugar in the D and L enantiomeric forms, respectively. Only the glycobiosyl NGP bearing the terminal sugar as the D-enantiomer interacted with antibodies to M. avium serovar 25, thus providing evidence for the absolute configuration of the sugar, and showing that the complete oligosaccharide hapten has the structure, O-(4-acetamido-4,6-dideoxy-2-O-methyl-alpha-D- galactopyranosyl)-(1-->4)-O-beta-D-glucopyranosyluronic acid-(1-->4)-O-(2-O methyl-alpha-L-fucopyranosyl)-(1-->3)-O-alpha-L- rhamnopyranosyl-(1-->2)-6-deoxy L-talose. PMID- 1284114 TI - Influence of corticosterone acetate on the spleen in intact and ovariectomized rats. AB - Increasing evidence of the interaction of glucocorticoids and ovarian steroids prompted the current study. Effects of exogenously administered corticosterone acetate (3.5 mg/100 g b.w/day for one week) were examined on splenic nucleic acids, protein, lactate, and on lactate dehydrogenase (LDH) specific activity and its isozymes in ovariectomized and ovary-intact Wistar rats (65-75 days old). Ovariectomy resulted in no significant change in the parameters studied except DNA which increased significantly. The administration of corticosterone to these rats did not produce any remarkable change in the ovariectomy caused increase in splenic DNA content. Nevertheless, it decreased the ratio of heart type subunits (H)/muscle type subunits (M) [H/M] of LDH isozymes. In the case of ovary-intact rats, corticosterone produced an increase in the concentration of splenic lactate but a decrease in the H/M ratio. Exogenously administered corticosterone exerts selective synergistic interaction with ovarian hormones on splenic lactate. The specific activity of LDH and the concentrations of RNA and protein remained unchanged during the interaction between ovarian hormones and corticosterone. PMID- 1284115 TI - Usefulness and limitation of measurement of insulin-like growth factor binding protein-3 (IGFBP-3) for diagnosis of growth hormone deficiency. AB - To analyze the utility of insulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay for diagnosis of growth hormone deficiency (GHD) we measured IGFBP-3 in sera from normal children, short children and patients with GHD. The sensitivity (true positive ratio) of IGFBP-3 for complete GHD (cGHD) was 93%, while the specificity (true negative ratio) for normal short children (NS) was 88%. In contrast, the sensitivity of IGFBP-3 for partial GHD (pGHD) was only 43%. The poor discrimination between patients with pGHD and NS may be the result of their relatively similar GH level, as compared to cGHD, or due to the limitations of GH stimulation tests. The specificity of IGFBP-3 for NS was excellent in children of all ages: less than 10 years old (87%) and older than 10 (88%). However, sensitivity for GHD was good for children less than 10 years old (84%) but poor for children older than 10 (64%). IGFBP-3 may be less sensitive for diagnosing GHD in older children because IGFBP-3 levels may also increase during puberty due to mechanisms independent of the GH-IGF-I axis. PMID- 1284116 TI - Anti-hepatitis C virus antibodies amongst Italian homo-bisexual males. AB - The authors report on an anti-hepatitis C virus antibody (HCV Ab) prevalence (6.9%) in 622 homo-bisexual males from Northern Italy, voluntarily attending an HIV and STDs screening program in the period 1984-89. The anti-HCV antibody prevalence shows a significant correlation with: i) presence of serological markers for HBV (O.R. = 3.12, 95% C.I. = 1.53-6.52) and HIV (O.R. = 12.09; C.I. = 6.52-22.52) infection; ii) a stable relationship with an anti-HCV antibody positive partner (O.R. = 7.79; 95% C.I. = 2.50-23.90); iii) more than twenty different male partners per year (O.R. = 2.55; 95% C.I. = 1.17-5.66). These data demonstrate the existence of a sexual transmission of HCV among homosexuals. This route might contribute in maintaining endemic levels of HCV infection in the homo bisexual population and it might represent an important way of spreading the virus in the general population too. PMID- 1284117 TI - [Hemodynamic and neuroendocrine profile of 2 different cardiovascular responses in vasodepressor syncope induced by the head-up tilt test]. AB - BACKGROUND: Syncope in apparently healthy subjects is usually attributed to a vasovagal reaction. However, a vagal cardio-inhibitory component is not always associated with a vasodepressor component in causing syncope: in fact, increases in heart rate, arterial pressure and plasmatic levels of catecholamines frequently precede loss of consciousness. METHODS: Prolonged 60 degrees head-up tilt table test (HUTT) was performed in 50 healthy subjects (27 male, 23 female - mean age 37.2 years) with recurrent syncope of vasodepressor or unknown origin. The upright-tilt test lasted 45 minutes: every minute of HUTT we measured heart rate (HR) and systolic (SBP) and diastolic blood pressure (DBP); at set intervals we took a blood sample to determine epinephrine (EP) and norepinephrine (NEP) levels. RESULTS: In patients with positive HUTT (42%) we observed a vaso-vagal response (10 patients) characterized by a sharp drop in SBP and DBP (> 50% of the basal values) and bradycardia (< 40 bpm) and/or sinus node arrests, and a hyperchronotropic-vasodepressor response (11 patients) characterized by a considerable increase in HR (> 60%) and simultaneous drop in SBP and DBP (> 30% of the basal values), and a large increase in plasmal EP (+881.9%). CONCLUSIONS: According to the Authors, vasovagal response is mainly due to a reflex reaction originating from the cardiac stretch-receptors, whereas hyperchronotropic vasodepressor response is mainly due to psychic stress and anxiety provoked by prolonged and forced posture during HUTT. The high levels of adrenergic activity and plasmal EP cause the excessive chronotropic response and the vasal effects of the syndrome. Due to the induction of a state of anxiety and its postural effects, HUTT is a useful provocative tool for complete evaluation of young patients with syncope of vasodepressor origin. We treated the patients differently, depending on how they responded to HUTT. Those with a vaso-vagal response were treated with alpha-sympathomimetic agents (ethylephrine or mydodrine) and those with a hyperchronotropic-vasodepressor response received non selective beta-blockers. None of our patients had syncope recurrences during a mean follow-up of 12.3 months. Only two patients complained of dizziness; in one of them, symptomatology was abolished by an alpha-sympathomimetic beta-blocker association. PMID- 1284118 TI - Bactericidal activity of two IgG2a murine monoclonal antibodies with distinct fine specificities for group B Neisseria meningitidis capsular polysaccharide. AB - To analyze the fine specificity of the protective IgG response for the capsule of group B Neisseria meningitidis (Men B) induced after immunization with live bacteria, two specific IgG2a monoclonal antibodies (mAb) have been generated from hyperimmunized Balb/c and NZB mice (101C11 and 30H12). They specifically recognize in direct and competitive binding assays the capsular polysaccharides of Men B and Escherichia coli k1 on condition that the length of the polysaccharidic chain is sufficient to make a conformational structure (more than 15 monomers of alpha (2-->8) linked N-acetyl neuraminic acid). They do not interact with group A and group C Neisseria meningitidis polysaccharides in ELISA. A chemical derivative of the Men B polysaccharide, the N-propionylated Men B polysaccharide, considered as mimicking a unique bactericidal epitope on the surface of Men B is recognized by 101C11 but not by 30H12. The two mAb have, in vitro, a specific bactericidal activity against live Men B which do not seem serotype specific. Moreover, the killing of Men B mediated by 30H12 can be neutralized by an anti-idiotypic mAb (216F11) generated from A/J mice, immunized with polymerized 30H12. These data show that at least two distinct bactericidal epitopes exist on the surface of the Men B capsule. PMID- 1284119 TI - Enhanced production of monoclonal antibodies against zona pellucida-free, unfertilized mouse oocytes by intrasplenic immunization. AB - Monoclonal antibodies were obtained by intrasplenic insertion of a total of 40-50 zona pellucida-free, unfertilized mouse oocytes into each mouse. The oocytes were prepared by a combined enzyme-mechanical method without impairing the fertility of the oocyte or inducing parthenogenesis. Of a total of 1063 hybrids obtained, 15 yielded supernatants with positive reactions to unfertilized oocytes. Tests for preimplantation stage specificity demonstrated that 9 of the supernatants detected antigen epitopes in unfertilized oocytes only. The other supernatants showed positive reaction patterns to various embryonal stages of the preimplantation period. Two supernatants recognized materials in the culture medium shedded by zona pellucida-free oocytes. Thus, by applying intrasplenic immunization, the production of antibodies against zona pellucida-free mouse oocytes is enhanced. The procedures described outline a rational way of selecting antibodies of interest for research in the mechanism of fertilization. PMID- 1284120 TI - Generation of monoclonal antibodies against a human T cell receptor beta chain expressed in transgenic mice. AB - The generation of a panel of monoclonal antibodies specific for different variable (V) regions of human T cell receptors will be of great importance in the study of T cell-mediated diseases. However, relatively few such reagents exist, due in part to the poor immunogenicity of TcRs on the surface of human T cells. We have employed a strategy in which T cells from a transgenic mouse line expressing a human V beta 3 C beta 1 TcR were used to immunise syngeneic conventional mice to generate two monoclonal antibodies specific for human T cell receptors. Binding of antibody JOVI.3, which stained approximately 5% of human peripheral blood CD3 positive T cells, correlated with the expression of the human TcR V beta 3 gene segment. Antibody JOVI.1 recognised a determinant on the majority of TcRs, staining 50-75% of peripheral blood T cells and T cell lines expressing different V beta regions. Some TcRs, however, failed to react with this antibody. Both antibodies immunoprecipitated detergent-solubilised TcR molecules and were capable of inducing proliferation of peripheral blood T cells. PMID- 1284121 TI - Equine tumor necrosis factor alpha: cloning and expression in Escherichia coli, generation of monoclonal antibodies, and development of a sensitive enzyme-linked immunosorbent assay. AB - We describe the production and purification of recombinant equine tumor necrosis factor alpha (rETNF alpha), generation and characterization of murine monoclonal antibodies (Mabs) and rabbit polyclonal antibodies (Pabs) against ETNF alpha, and development of a sensitive enzyme-linked immunosorbent assay (ELISA). Genomic derived DNA sequences encoding mature ETNF alpha were reconstructed by the polymerase chain reaction (PCR) and oligonucleotide-directed mutagenesis and were cloned into the vector pFLAG-1 for expression in Escherichia coli. rETNF alpha was purified by anti-FLAG immunoaffinity chromatography and then used as immunogen for production of murine Mabs and rabbit Pabs. Three Mabs (6H4, 9B10, and 12F6) were obtained from one fusion. All three Mabs recognized rETNF alpha on western blots. Mabs 6H4 and 9B10 recognized similar epitopes on rENTF alpha and neutralized both rETNF alpha and native ETNF alpha (nETNF alpha) in a WEHI cell cytotoxicity assay. A sensitive ELISA was developed using Mab 6H4 and biotin labeled rabbit Pabs. The ELISA was shown to detect levels of ENTF alpha as low as 100 pg/ml and was used to demonstrate the induction of ETNF alpha in horses with experimental endotoxemia. The rETNF alpha, antibodies, and ELISA developed in this report should be useful tools for studies of TNF-mediated diseases in horses. PMID- 1284122 TI - A monoclonal antibody (IID510g52) for the determination of functional domains within integrin cell surface receptors. AB - Monoclonal antibodies against cell surface receptors can be useful for the study of structural and biochemical features involved in protein interactions underlying platelet adhesion and aggregation. We report here the characterization of a monoclonal antibody, IID510g52 (hereafter referred to as IID5), which has been selected based on its specific binding properties against the platelet membrane glycoprotein IIIa. Characterization of the reactive epitope, including evolutionary conservation and identification of related IID5 target antigens in tumor cells, suggest that the IID5 epitope is implicated in the ligand-binding function of integrin receptors. Indeed, we show that this MoAb acts as a potent inhibitor of platelet aggregation and cell adhesion. Taken together, these results indicate that such a monoclonal may be a strategic tool for better understanding multiple integrin-mediated adhesive reactions, as well as the determination of interacting recognition sites. PMID- 1284123 TI - Antigen specificity and cross-reactivity of fifteen monoclonal antibodies against porcine pancreatic alpha-amylase II and its AB and C domains. AB - Highly productive hybridoma secreting mabs specific for porcine alpha-pancreatic amylase II were established. Fifteen clones were selected. The mabs produced (KD = 1.68-11.2 nM) were checked for cross-reactivity with six heterologous antigens, namely porcine pancreatic alpha-amylase I, barley amylase, human pancreatic alpha amylase, Taka amylase and triose phosphate isomerase, using direct ELISA assay; mabs were classified within seven groups: in a few groups mabs cross-reacted with a single heterologous antigen either porcine pancreatic amylase I (6 mabs) or barley amylase (2 mabs) or human pancreatic amylase (3 mabs). Two other groups cross-reacted with two heterologous antigen either porcine I and human or porcine I and barley. Only one mab out of fifteen cross-reacted in direct ELISA binding to all amylases and triose phosphate isomerase. Using sandwich ELISA test only three mabs were found to bind porcine amylase II present at high concentration. Results consistent with direct porcine amylase binding were obtained from binding inhibition assays. Analysis by the additivity test allowed to find that 3 mabs, B10.10, B1.11, C6.4 recognize distinct epitopes while the epitopes for the other pairs tested are either overlapping or at least close to each other. Finally mabs binding specifically either to the AB or to the C domain fragment or to both fragments have been obtained. PMID- 1284124 TI - Monoclonal antibodies to human thyroglobulin: evaluation of immunoreactivity. AB - We have earlier reported production and characterization of monoclonal antibodies (MAbs) to human thyroglobulin (h-tg). In the present study H10 I MAb was evaluated for its immunoreactivity towards different forms of tg and various human thyroid tumours. The specificity of H10 I MAb was validated by the absence of cross reaction with tri-iodothyronine (T3) Thyroxine (T4) and human gamma globulins. Sodium-dodicyl-sulphate polyacrylamide gel electrophoresed (SDS-PAGE) immunoblot of h-tg on the nitrocellulose membrane revealed multiple immunoreactive bands on reaction with polyclonal antibody (PAb) in comparison with total lack of reactivity with H10 I MAb. The absence of immunoreactivity of H10 I MAb was demonstrated with SDS treated, Dithiothreitol (DT) treated and heat denatured tg using dot immunobinding technique. However, the H10 I MAb was able to react with tg treated with unfolding agents such as urea and guanidine hydrochloride. All the treated forms of tg were equally recognized by PAb. The immunoreactivity of the oxidized/reduced tg towards H10 I MAb was markedly reduced (60.0%) as compared to that obtained with native tg. It appears that H10 I MAb is directed towards conformational epitope involving sulphydryl bonds. Immunohistochemically, a comparable immunoreactivity between PAb and MAb was observed with normal thyroid tissues, follicular thyroid tissues, Hurthle cell carcinoma tissues and poorly differentiated thyroid tumor tissues using immunoperoxidase staining. The sections from papillary carcinoma tissue (thyroid as well as metastatic lymph node) exhibited intense immunoreactivity with PAb. Thyroglobulin present on these sections was not recognized by H10 I MAb. Nonetheless, H10 I MAb was able to detect tg in follicular differentiation wherever present. The absence of immunoreactivity of H10 I MAb in papillary carcinoma strongly suggests that this neoplasm produces tg which is antigenically different from the protein present in the normal tissue. The reactivity of H10 I MAb with metastatic lymph node of an unknown primary origin suggests its usefulness in the identification of prevalent metastasis of differentiated thyroid carcinoma other than papillary type. PMID- 1284125 TI - Epitope specificity of monoclonal antibodies against Newcastle disease virus: competitive fluorogenic enzyme immunoassay. AB - A test to determine the epitope specificity of monoclonal antibodies (MCA) was developed for hybridoma clones producing antibodies against Newcastle disease virus (NDV). The virus was first immobilized on nitrocellulose membranes of Millititer HA plates. Dilutions of MCA were then added, singly, or simultaneously in pairs, and bound antibody was quantitated with alkaline phosphatase-labelled detector antibody and a fluorogenic substrate, 4-methylumbelliferyl phosphate (4 MUP). Fluorescence count was measured fluorometrically. Additivity indices were calculated and plotted against dilutions of paired MCA. Antibodies that recognized identical epitopes displayed non-additivity at saturating antibody dilutions, followed by partial additivity and by total additivity at low, non saturating dilutions. In contrast, MCA that recognized distinct epitopes exhibited total additivity throughout the curve. MCA that exhibited partial additivity were interpreted as competing for overlapping shared epitopes, or, distinct epitopes in close proximity, resulting in steric hinderance. PMID- 1284127 TI - Variability of muscle fibre composition and fibre size in the horse gluteus medius: an enzyme-histochemical and morphometric study. AB - To determine the variability in fibre types and fibre sizes in the equine gluteus medius muscle, biopsy specimens were removed from 5 sites, at 4 different depths, within the right and left muscles of 3 Andalusian stallions. The percentage, lesser fibre diameter and cross-sectional area of the various fibre types were measured systematically in myosin ATPase and NADH-tetrazolium reductase-stained, serial cryostat sections of these multiple samples. Significant differences in muscle fibre type composition were recorded, with a lower percentage of type I fibres (high myosin ATPase activity at pH 4.5) being observed towards superficial regions of the muscle and a greater percentage towards the deep areas. Type II B fibres (moderate myosin ATPase activity at pH 4.5), including both II B nonoxidative (low NADH-TR activity) and II B oxidative (moderate NADH-TR activity), displayed the opposite tendency, and the percentage of type II A fibres (low myosin ATPase activity at pH 4.5) did not change with depth. Types I and II A fibres in the deep regions were larger than superficially, whereas the II B fibres in the deep regions were smaller than in the superficial parts of the muscle. The results also imply that type I fibres tend to be larger than type II fibres in the deep regions. The size of type I fibres is more homogeneous in the deep parts than in the superficial regions of the muscle, while II B fibres vary more in size in the peripheral portions than in deep regions. A single biopsy taken from the gluteus medius muscle of the horse is therefore a poor representative of the whole muscle and care should be exercised in sampling and interpreting data obtained from limited biopsy of this muscle. The pattern of variation in fibre types and fibre sizes between the different depths of the muscle probably reflect different functional demands on the gluteus medius muscle. PMID- 1284126 TI - Effect of phorbol ester and cytokines on matrix metalloproteinase and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines. AB - The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) on matrix metalloproteinases (MMP) and metalloproteinase inhibitors was studied in a variety of human cell lines. Expression of the mammalian collagenase (MMP-1), 72 kD gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), 92-kD gelatinase/type IV collagenase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was assessed by zymography and Northern blot analysis. MMP-2 and TIMP-2 activities were refractory to TPA, IL-1 and TNF alpha treatment in most of the cell lines. In contrast, MMP-3, MMP-9 and TIMP-1 activities were markedly stimulated by TPA in most of the tumor cell lines and human umbilical vein endothelial cells (HUVEC), whereas the fibroblast lines were minimally stimulated or unresponsive to TPA. The MMP-3, MMP-9 and TIMP-1 stimulation in response to IL-1 and TNF-alpha treatment was detected in some of the tumor cell lines and HUVEC. The increase in activity was less marked than in TPA. A breast carcinoma cell line, MDA-MB-231, which did not express MMP-2, had high expression of MMP-3 and MMP-9 which were unaffected by TPA and cytokine treatment. Northern blot analysis of MMP and TIMP mRNA expression reflected the zymogram findings for most of the cell lines. TPA-mediated stimulation of MMP-1 was similar to that of MMP-3 and MMP-9. Exceptions were the fibroblast cell lines which showed either a much more marked mRNA response of MMP-9 to TPA than observed at protein level, or a high constitutive MMP-9 mRNA when MMP-9 activity was not detectable by zymography. TPA-mediated stimulation of MMP-9 and TIMP-1 activity was blocked by staurosporine, an inhibitor of protein kinase C (PKC). A non-PKC-activating phorbol ester, 4 alpha-phorbol-12,13-didecanoate, did not stimulate MMP-9 and TIMP-1 activity. TPA treatment caused the increased expression of c-fos containing AP-1-specific binding activity in selected tumor cell lines. This activity was maximal at 6 h. An association was observed between AP-1 binding activity and increased expression of MMP-1, MMP-3 and MMP-9, which possess TPA-responsive elements (TRE). TPA-sensitive MMPs and TIMP-1 were variably stimulated by biologically relevant cytokines, such as IL-1 and TNF alpha.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284128 TI - Immunocytochemical localisation of substance P in vagal ganglion cells and pericellular arborisations in the monkey. AB - The quantitative cell count showed the presence of about 20,000 ganglion cells with associated satellite elements in the nodose ganglion in the monkey. Among these closely packed cells, at least one-third were substance P (SP) immunoreactive, ranging from faint or moderate to intense staining. Substance P immunoreactivity (SP-IR) was localised in the cell bodies and their long extending neurites. Ultrastructural study showed that SP-IR was not associated with any particular organelles or inclusions. A striking feature of the nodose ganglion was the occurrence of SP-positive pericellular arborisations associated with about 0.5% of the ganglion cells which were almost exclusively SP-negative. The pericellular arborisation displayed diverse morphological forms from a simple tortuous fibre to complex glomerular networks or plexuses encircling the soma of SP-negative ganglion cells. The varicose nerve fibres forming the pericellular arborisations appeared to terminate as 'boutons' contacting the soma of the ganglion cells. Electron microscopic study demonstrated the close spatial relation between the SP-IR profiles and the ganglion cell but there was no direct synaptic contact. In some instances, the SP-IR profiles containing agranular and dense-cored vesicles penetrated the cytoplasm of satellite cells, almost reaching the surface of the soma of the ganglion cell. The sources of origin of the nerve plexuses in the pericellular arborisation were either from the small and sparsely distributed jugular ganglion cells which were intensely SP-IR or from the intrinsic SP-IR nodose ganglion cells. The possibility that the efferent neurons in the dorsal motor nucleus of the vagus could also contribute to the pericellular arborisation was also considered. The function of the pericellular arborisations may be related to the modulation of the SP-deficient ganglion cells with which they associate through the release of SP and probably by way of the satellite cells. PMID- 1284129 TI - On the physiological significance of tumor necrosis factor-alpha in the human amniotic fluid. AB - Tumor Necrosis Factor (TNF)-alpha and Interleukin (IL)-1 beta levels have been measured in 16 weeks gestation amniotic fluids and mother's sera. Detectable levels of TNF-alpha were found in amniotic fluids, while IL-1 beta was absent. No cytokines were detected in mother's sera. The possible role of TNF-alpha as growth factor for fetal hematopoietic cells is discussed. PMID- 1284130 TI - Simultaneous appearance of a unique common epitope in fetal colon, skin, and biliary epithelial cells. A possible link for extracolonic manifestations in ulcerative colitis. AB - The tissue distribution of a previously identified M(r) 40 K epithelial autoantigen in ulcerative colitis was examined in situ in the fetal tissue by immunocytochemical method, using an immunoglobulin M (IgM) monoclonal antibody (7E12H12). Fetal-autopsy tissue from 9 to 19 weeks of development (11-21 gestational weeks) gestations, including specimens of colon (20 specimens), skin (19), small intestine (12), gallbladder (15), liver (20), spleen (20), kidney (3), urinary bladder (3), and umbilical cord/placenta (25) were examined. 7E12H12 reactive epitope appeared first in a few colonic epithelial cells at 10 weeks of gestation. By 11 weeks, 7E12H12 reactivity was clearly evident in most of the colonic epithelial cells. Goblet-cell reactivity was evident from 15 weeks of gestation. Enterocytes lining the small intestine from all the specimens were negative. In the skin, earliest immunoreactivity was evident in the basal layer of epidermis at 10 weeks of development, and by 11 weeks, the staining was intense and localized exclusively to squamous epithelial cells of the epidermis. The immunoreactivity in the fetal gallbladder mucosa was also evident earliest at 11 weeks of development. The staining was distinct in the mucosal epithelial cells, and localized along the periphery of the cells and in the apical areas. None of the other tissue specimens reacted with 7E12H12. These results demonstrate that the 7E12H12 reactive epitope is novel, is shared by colon, skin, and biliary epithelium, and appears more or less simultaneously in the three organs at 10 to 11 weeks of development of the fetus. A possible link of this crossreactive protein or proteins in the immunopathogenesis of ulcerative colitis, sclerosing cholangitis, and pyoderma gangrenosum is discussed. PMID- 1284131 TI - Synergistic effect of 1,25-dihydroxyvitamin D3 and retinoic acid in inducing U937 cell differentiation. AB - We examined the effects of retinoic acid (RA), 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3), and its synthetic analogue, 22-oxa-1,25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, 1,25-(OH)2D3 did not inhibit cellular growth, but increased CD 14-positive cells. Simultaneous addition of 1,25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD14 expression. With regard to [Ca2+]i, however, 5 days' incubation with either of them increased the basal [Ca2+]i level and induced U937 cells to respond to formyl-methionyl-leucyl phenylalanine (FMLP). When the cells were incubated with both 10(-6) M RA and 10( 8) M 1,25-(OH)2D3, basal [Ca2+]i was higher and FMLP caused a greater increase in [Ca2+]i than when only RA or 1,25-(OH)2D3 was added. These data suggest that RA and 1,25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. The 22 oxa-1,25-(OH)2D3 induced CD14 expression, basal [Ca2+]i increase and [Ca2+]i response to FMLP, but did not cause cellular growth inhibition in U937 cells, and in these points, 22-oxa-1,25-(OH)2D3 exhibited no significantly different effects from 1,25-(OH)2D3. Thus, 22-oxa-1,25-(OH)2D3 has the same potent activity as 1,25 (OH)2D3 in inducing differentiation of U937 cells. PMID- 1284132 TI - Abnormal glycosylation of hemopexin in arthritic rats can be blocked by bindarit. AB - Induction of arthritis in rats with Freund's complete adjuvant was accompanied by a distinctive alteration of concanavalin A (Con-A) reactivity in their serum proteins in which the concentrations of selected Con-A reactive proteins were significantly higher when compared to healthy rats. To assess if the observed increase in Con-A reactivity of specific serum proteins reflects an increase in carbohydrate moieties in these proteins in addition to an increase in their protein concentrations, a heme binding serum glycoprotein, hemopexin, also an acute phase reactant, was selected as a marker protein. Hemopexin was purified to apparent homogeneity from pools of serum samples derived from rats with yeast induced inflammation, a monospecific polyclonal antibody was prepared and was used for immunoblot analysis. It was noted that the concentration of hemopexin increased in rats with adjuvant induced arthritis; however, its concentration fell to normal levels after administration with a newly synthesized drug, bindarit, (2-[(1-benzyl-indazol-3-yl)methoxy]-2-methyl propionic acid, C19H20N2O3. Hemopexin was micropurified individually from healthy rats, adjuvant induced arthritic rats, and adjuvant arthritic rats treated with bindarit, cleaved with a Glu-C endopeptidase, Staphylococcus aureus protease V8, and the resultant peptide fragments resolved by SDS-PAGE and examined by silver staining, Coomassie blue staining, and lectin blots using Con-A. It was subsequently noted that hemopexin isolated from adjuvant induced arthritic rats showed a significant increase in Con-A reactivity in selected peptide fragments and that such an increase in glycosylation could be reversed to a pattern similar to healthy rats following treatment with bindarit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284133 TI - Immunologic effects in patients with psoriatic arthritis treated with cyclosporine A. AB - Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections. PMID- 1284134 TI - [Reconstruction of glomerular tufts--observation of mesangiolysis induced by anti thymocyte serum]. AB - The reconstruction process of the glomerular capillary structure following mesangiolysis induced in rats by anti-thymocyte serum (ATS) was investigated for three months. Cystic ballooning change of the glomerular tufts was remarkable four days after the administration of ATS, which was followed by inflammatory cell infiltration, and hypercellularity in mesangial area was observed one week later. Glomerular tufts were gradually reconstructed thereafter, leaving focal and segmental sclerotic or adhesive lesions. In the periphery of the ballooning area, a large vascular lumen was subdivided into smaller capillary lumina by endothelial and mesangial bridging, which resembled to the process in the fetal glomerulogenesis. The endothelial cells in mesangiolysis connected one another by junctional complexes and formed new capillary structure. The mesangial cells got in touch with the endothelial cells by mesangial bridging. In the proliferative lesion, endothelium-like cells could be recognized by immunostaining and had fenestrae with diaphragmatoid structure without mature basement membrane in the initial stage on electron microscopic observation. Interstitial-typed collagen fibers were found in the proliferative lesion, and they still existed in the focal segmental sclerotic lesion in the late stage of the experiment. The glomerular basement membrane (GBM) was seen to be reformed by fusing the original GBM with the newly synthesized one covering subendothelial space, where mesangial cells were interposed. Endothelial cells, endothelial-mesangial interaction and extracellular matrix formation seemed to play an important role in reconstruction of the glomerular tufts after mesangiolysis induced by ATS. PMID- 1284135 TI - [The use of kontrikal in treating unstable stenocardia by specialized first-aid teams]. AB - The paper presents the results of unstable angina pectoris treatment in 121 patients who received or did not receive (65 and 56 patients, respectively) contrykal in a dose of 20,000 units as an adjuvant to standard treatment (analgetics, tranquilizers, vasodilators). All the patients were admitted to cardiological departments. The comparative assessment of the data favours contrykal infusions in emergency prehospital care of developing unstable angina pectoris. The drug produces a cardioprotective effect reducing the risk of macrofocal myocardial infarction. PMID- 1284136 TI - A solid phase extraction technique for the isolation and identification of opiates in urine. AB - A quantitative method was developed for the simultaneous analysis of morphine, codeine, hydromorphone, hydrocodone, and oxycodone in urine by gas chromatography/mass spectrometry. Samples were hydrolyzed with beta-glucuronidase and then extracted by solid phase extraction on Bond Elute Certify cartridges at pH 6.8. Nalorphine was used as the internal standard. The opiates were analyzed by full-scan electron impact GC/MS after derivatization with acetic anhydride pyridine. The standard curves for all five drugs were linear between 50 and 1000 ng/mL, with correlation coefficients exceeding 0.99. Coefficients of variation were less than 7%. The method was applied to the analysis of postmortem urines positive by EMIT opiate assay, and the effect of the hydrolysis procedure on recovery of each drug was measured. The results indicate that the hydrolysis procedure is effective in increasing the recovery of all five drugs from urine. The described method enables the laboratory to identify the five opiates most commonly encountered in forensic and clinical laboratories. Its sensitivity for all five drugs is well below GC/MS cutoffs for codeine and morphine employed in NIDA laboratories, and it provides for conclusive full-scan drug identification. PMID- 1284138 TI - Insulin sensitivity: cardioprotection vs. metabolic disorders. Workshop held in Hamburg, Germany, May 1, 1992. PMID- 1284137 TI - Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. AB - Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease. PMID- 1284139 TI - Determination of insulin sensitivity: methodological considerations. AB - During the past decade, it became obvious that in contrast to defective insulin secretion in type I diabetes, defective insulin action (insulin resistance) is the most pertinent feature of type II diabetes. In addition, it has been known for a long time that obesity and insulin resistance are closely linked. Recently, hypertension also has been shown to often coincide with insulin resistance, although any causal relationships are still hypothetical. Last, several widely used pharmacological drugs such as diuretics, adrenergic blockers, and angiotensin-converting enzyme inhibitors may influence insulin sensitivity. Therefore, growing interest has emerged to most accurately measure insulin sensitivity. Although considerable knowledge has accumulated as to the actual mechanisms of insulin-dependent glucose transport, the signal transduction pathway of insulin remains poorly understood. When insulin sensitivity is measured, it is the overall glucose uptake that is quantified under controlled conditions. Other actions of insulin, such as the transport of ions, (e.g., sodium and potassium), synthesis of insulin-like growth factor-binding proteins, translocation of transporter proteins, and regulation of enzyme activities, are much more difficult to quantify. Of the many approaches used to quantify insulin action, the euglycemic hyperinsulinemic clamp technique has emerged as the most reliable tool, fulfilling clinical and scientific demands equally. In combination with tracer methodology and calorimetry, a detailed view into the quantitative aspects of insulin action at different target cells is possible. Whether insulin resistance extends to other known actions of insulin in addition to those on glucose metabolism remains open to debate. PMID- 1284140 TI - What is the clinical significance of insulin resistance? AB - Insulin resistance is a frequent phenomenon and a marker of increased risk for non-insulin-dependent diabetes mellitus (NIDDM) and atherosclerosis. According to recent estimations, not only individuals with obesity, NIDDM, and impaired glucose tolerance (IGT) but also one fourth of the "healthy" glucose tolerant and the majority of the hypertensive population are insulin resistant. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. The initial defect can be directly measured by glucose clamp and other sophisticated techniques; the clinical syndrome may be derived from a network of related variables known to be associated with reduced insulin action. Because neither clamps nor serum insulin screenings will be available on a widespread basis, early diagnosis based on clinical criteria is crucial. A new interpretation of the "thrifty" genotype hypothesis may explain why insulin resistance, which formerly apparently represented an advantage in the evolutionary selection process, is such a frequent phenomenon. Improvement of impaired insulin action as a therapeutic principle may play a future central role in an integrated lifestyle approach of primary prevention of noncommunicable diseases such as NIDDM, hypertension, and atherosclerosis. PMID- 1284141 TI - Effects of nonpharmacological intervention on insulin sensitivity. AB - Hyperinsulinemia and insulin resistance have been implicated to play a role in the development of hypertension and to contribute to the increased risk for cardiovascular disease in diabetic, obese, hypertensive, and normotensive salt sensitive humans. Reviewed herein are the effects of nonpharmacological measures, including exercise, weight loss, diet, and changes in lifestyle, on insulin resistance. Based on the evidence from both experimental and clinical studies, regular exercise, moderate weight reduction, and a low-fat, high-carbohydrate, high-fiber diet can markedly improve insulin sensitivity. The possible mechanisms involved are discussed. Because these nonpharmacological measures have also been shown to lower blood pressure and correct dyslipidemia, they can contribute substantially to the reduction of major cardiovascular risk factors and should be implemented in all patients who may be at risk for cardiovascular disease. PMID- 1284142 TI - Angiotensin-converting enzyme inhibitors and insulin sensitivity: metabolic effects in hypertension, diabetes, and heart failure. AB - Angiotensin-converting enzyme (ACE) inhibitors are established in the treatment of hypertension and heart failure; both conditions are complicated by resistance to insulin-mediated glucose disposal. The defect in essential hypertension is both tissue and pathway specific, i.e., confined to nonoxidative (glycogen synthetic) routes of intracellular glucose utilization in skeletal muscle, whereas heart failure and non-insulin-dependent diabetes mellitus (NIDDM) are associated with more widespread abnormalities of carbohydrate and lipid metabolism. Thus, the mechanisms of the insulin resistance in hypertension, NIDDM, and heart failure are fundamentally different, so metabolic responses to drug therapy may not be the same in all insulin-resistant states. There have been conflicting reports about the effects of ACE inhibitors on insulin sensitivity and glycemic control. A number of studies, both with captopril and with enalapril, have shown small increases in insulin sensitivity, and there is evidence that this is due to enhanced glucose uptake into skeletal muscle. The interpretation of these studies, however, is often compromised by poor trial design, lack of full placebo data, various indirect measurements of insulin sensitivity, and heterogeneous patient populations in whom the biochemical mechanisms of insulin resistance (and drug responses) may not be the same. Overall, there probably is a modest class effect of ACE inhibitors that enhances insulin-mediated glucose disposal; the mechanism of this effect is likely to be a combination of increased muscle blood flow, local renin-angiotensin system blockade, and elevated kinin levels. PMID- 1284143 TI - Effects of antihypertensive treatment with beta-blockers on glucose metabolism. AB - The beneficial effects of beta-blockers on morbidity and mortality in both essential hypertension and diabetes mellitus have been demonstrated in several antihypertensive trial. Recently, negative side effects of beta-blockers on glucose metabolism have been suggested that could limit their wide-spread use. However, on detailed analysis, any side effects of beta 1-selective beta-blockers on glucose metabolism do not appear to be relevant for clinical practice and hence do not restrict the use of these agents as first-line antihypertensive drugs in diabetic and nondiabetic patients. PMID- 1284144 TI - Influence of diuretics, calcium antagonists, and alpha-blockers on insulin sensitivity and glucose tolerance in hypertensive patients. AB - Treatment with thiazide diuretics causes impaired glucose tolerance, biochemical diabetes, and insulin resistance. The effect of diuretics on glucose tolerance is clearly dose-related. Spironolactone does not impair glucose tolerance, even at high dosage, but differences among other diuretics could be due to comparisons at doses that are not equal. Diuretic-induced changes in glucose metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs even when relatively low doses of thiazide are combined with potassium-sparing agents. The effects of diuretics on glucose homeostasis are in large part and probably entirely reversible. These disturbances of glucose metabolism have been detected only by detailed biochemical testing, and their clinical relevance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In nondiabetic subjects, diuretics rarely cause or trigger a serious hyperosmolar nonketotic diabetic syndrome. Otherwise, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long term. Evidence from large outcome trials suggests that biochemical diabetes, glucose intolerance, and insulin resistance do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes unless their use is essential. Otherwise, a low dose of thiazide remains as excellent choice for first-line antihypertensive therapy. Dihydropyridine calcium antagonists, diltiazem, and verapamil appear to have no important effects on glucose homeostasis. There is very limited evidence that selective alpha antagonists increase insulin sensitivity. The importance of metabolic differences between drug classes will be established only by comparative outcome trials with coronary events as the end point. PMID- 1284145 TI - Beta-blockers: primary and secondary prevention. AB - Coronary heart disease is the most frequent cause of death in Western, industrialized countries. Coronary risk factors are prevalent in such countries and sometimes combine to constitute the so-called syndrome X--hypertension, central obesity, serum lipid and clotting disturbances, and insulin resistance. beta-Blockers, unlike calcium antagonists, have proved highly effective in secondary prevention of myocardial infarction. If present at the time of the myocardial infarction, beta-blockers (unlike calcium antagonists and diuretics) probably decrease mortality 1 month later. Early intervention (within 12 h) of chest pain with intravenous beta-blockers results in a 15% reduction in cardiovascular mortality at 1 week. Later intervention (3-28 days) with oral non ISA beta-blockers results in a 30% reduction in mortality after 1 year; ISA containing beta-blockers are probably less effective (less decrease in heart rate). Hydrophilicity/lipophilicity of beta-blockers is unimportant in terms of decreased mortality. Primary prevention of myocardial infarction, unlike stroke, in hypertensive patients has been disappointing, possibly due to treatment induced biochemical/lipid changes or inappropriate lowering of diastolic blood pressure in high-risk subjects (J-curve effect). beta-Blockers should be first line therapy for hypertensive patients up to the age of 65 years, particularly men (and nonsmokers) as Q-wave myocardial infarction is significantly decreased by beta-blockers and significantly increased by diuretics. However, in elderly hypertensive subjects, beta-blockers have not significantly decreased myocardial infarction (unlike stroke), whereas diuretics have. The effects of beta-blockers and diuretics on heart size (and thus coronary flow reserve) in the elderly may be important. Thus, beta-blockers should be second-line therapy for the elderly hypertensive individual but first-line if overt ischemia (e.g., angina or recent myocardial infarction) also is present. In patients with angina but normal blood pressure, beta-blockers tend to decrease and calcium antagonists increase cardiovascular events. Thus, beta-blockers are highly effective agents in the secondary prevention of myocardial infarction and are moderately effective in primary prevention of myocardial infarction in hypertensive patients (particularly men) under the age of 65 years. PMID- 1284146 TI - New antihypertensive agents: benefit of treatment. AB - Large-scale end-point trials have demonstrated that antihypertensive treatment reverses the risk of stroke attributable to high blood pressure and probably reduces the incidence of myocardial infarction. Despite this major achievement in therapeutics, substantial goals still need to be achieved. Thus, there is a need for improvement in existing antihypertensive agents in terms of greater blood pressure-lowering efficacy and improved impact on coronary heart disease in younger subjects. There is also a pressing need for a reduction in adverse effects. The incidence of these far exceeds the potential benefit of treatment. Last, the costs of therapy are assuming growing importance in the face of tight financial constraints on health care systems throughout the world. PMID- 1284147 TI - Hypertension and insulin resistance. AB - Insulin resistance and hyperinsulinemia is now recognized in non-insulin dependent diabetes, essential hypertension, obesity, atherosclerotic heart disease, dyslipidemia, heart failure, and in heavy smokers. Several mechanisms have been proposed to explain hyperinsulinemia, insulin resistance and its relationship to hypertension; reduced sodium excretion, activation of the sympathetic nervous system, increased activity of the sodium/hydrogen pump, and stimulation of cellular growth. Some of the nonpharmacological methods to control hyperinsulinemia are of benefit in the management of hypertension, most notably weight loss, exercise program, and reduced salt intake. High-fiber and reduced protein diets also reduce hyperinsulinemia. Thiazide diuretics can result in insulin resistance, and insulin secretion may be inhibited, possibly associated with concomitant hypokalemia. beta-Blockers result in some reduction of glucose tolerance and mask some of the features of hypoglycemia. Angiotensin-converting enzyme (ACE) inhibitors and alpha-receptor blockers do not effect insulin resistance; probably the same is true for calcium antagonists. Although the effect on risk factors should not be discounted, it is the effect of treatment on hard end points, cerebrovascular accidents, myocardial infarction, or death that is most important. Evidence in hypertension is at present restricted to diuretics and beta-blocking drugs. PMID- 1284148 TI - Gallopamil: cardiovascular scope of action of a highly specific calcium antagonist. AB - According to Fleckenstein's original classification, gallopamil represents a prototype of highly specific calcium antagonists of Group A. Its large scope of cardiovascular effects is lastly based on one and the same mechanism of action: inhibition of transmembrane calcium influx into myocardial, cardiac pacemaker, and vascular smooth muscle cells. Thereby, in experimental studies that use electrophysiological, biochemical, isotopic, and histological techniques, gallopamil reduced calcium-dependent myocardial contractility and oxygen consumption; dampened nomotopic and ectopic cardiac pacemaker activity; exerted pronounced vasodilator effects; and protected myocardial cells from calcium overload-induced necrotization. The effects of gallopamil on myocardium, cardiac pacemakers, and vasculature are quantitatively comparable, surpassing those of verapamil by approximately one order of magnitude. Further clinical studies must demonstrate to what extent humans will benefit from the experimentally proven cardiovascular potential of gallopamil. PMID- 1284149 TI - New experimental and clinical results on calcium antagonism. Proceedings of the 2nd International Gallopamil Symposium. Paris, November 8-9, 1991. PMID- 1284150 TI - Effect of gallopamil on cardiac sarcoplasmic reticulum. AB - We investigated the effect of gallopamil on cardiac sarcoplasmic reticulum (SR) function. Heavy SR was prepared from bovine ventricular muscle. Oxalate-supported calcium uptake was stimulated by gallopamil at concentrations ranging from 10 to 300 nM, whereas higher concentrations were ineffective. Peak stimulation averaged 25-30% of control calcium uptake and was observed at free calcium concentrations ranging from 1 to 6 microM. Calcium uptake is actually the difference between active calcium transport by SR calcium-adenosine triphosphate (calcium-ATPase), and passive efflux through SR calcium-release channels. In the presence of 300 microM of ryanodine, a blocker of SR channels, calcium uptake increased by 43% under control conditions, but not further stimulation was produced by gallopamil. SR calcium-ATPase was not affected by gallopamil. Similar results were obtained when oxalate-supported calcium uptake was determined with use of unfractionated homogenate obtained from rat hearts. We conclude that gallopamil acts on SR calcium-release channels and reduces the probability of channel opening and/or channel conductivity. The dose-response curve is bell shaped, and the maximum effect, which corresponds to 65% of the maximum effect of ryanodine, is achieved at therapeutic concentrations. Such action might contribute to the beneficial effect of gallopamil in the treatment of myocardial ischemia. PMID- 1284151 TI - Calcium antagonism and norepinephrine release in myocardial ischemia. AB - In myocardial infarction, adrenergic stimulation of the heart is thought to cause cell damage and malignant arrhythmias. In rat hearts as well as in human cardiac tissue, ischemia induces norepinephrine (NE) release, which results in micromolar catecholamine concentrations in the interstitial space of the ischemic myocardium. It has been found that local metabolic, rather than centrally evoked NE release, plays the crucial role in excess adrenergic activation of the ischemic myocardium. NE release in ischemia is nonexocytotic and has been characterized as a two-step process. (a) Induced by energy deficiency, NE escapes from its storage vesicles and accumulates in the axoplasm. (b) NE is transported across the plasma membrane into the extracellular space via the neuronal NE carrier (uptake1), which has reversed its normal transport direction because of increased intracellular sodium concentration. NE release induced by ischemia is independent of the presence of calcium in the extracellular space and is not altered by blockade of N-type (neuronal) calcium channels. Furthermore, modulation of protein kinase C does not interfere with NE liberation in the ischemic myocardium. This independence of extracellular calcium, calcium entry into the neuron, and protein kinase C activity is in contrast to the strong calcium dependence of exocytotic transmitter release, which is found under physiological conditions. On the basis of these findings, it was unexpected that calcium antagonists such as gallopamil, verapamil, diltiazem, felodipine, and nifedipine suppress ischemia-induced NE release. The most potent effect was found for gallopamil with a concentration of 50% inhibition (IC50) of 300 nmol/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284153 TI - Calcium antagonists and experimental myocardial ischemia reperfusion injury. AB - A number of previous studies have reported that administration of calcium antagonists reduces acute ischemic injury in a variety of experimental models. More recently, however, it has been suggested that the beneficial effects of reperfusing the ischemic myocardium might be blunted by the paradoxical occurrence of a specific form of reperfusion-mediated injury. Although the ultimate mechanisms responsible for this phenomenon have not been completely elucidated, it has been suggested that oxygen radical generation, neutrophil activation, and calcium overload, may all contribute to the development of myocardial damage in postischemic hearts. Several experimental studies suggest that, in addition to their well-known effects on ischemic injury, calcium antagonists may variably affect these mechanisms of reperfusion-mediated cell damage. In particular, evidence has been provided that suggests these drugs may inhibit oxygen radical-mediated peroxidation of membrane lipids and may also reduce activation of stimulated neutrophils. Furthermore, calcium-channel blockers might also prevent calcium overload in reperfused hearts, and they might interfere with reperfusion injury indirectly, secondary to a reduction in the severity of ischemia. From the experimental data available it can be speculated that calcium antagonists might contribute to reducing oxygen radical damage following reflow. At the same time, these drugs may allow the extension of the time window of reperfusion therapy, thus further expanding the benefits of thrombolysis. PMID- 1284152 TI - Effect of gallopamil on neutrophil function: experimental and clinical studies. AB - The purpose of the study was to investigate whether gallopamil interferes with neutrophil activation. In vitro, gallopamil caused a dose-dependent reduction in phorbol myristate acetate-stimulated superoxide anion production by neutrophils as measured by the superoxide dismutase inhibited reduction of cytochrome C [concentration of 50% inhibition (IC50) = 9.5 x 10(-6) mol/L]. Furthermore, gallopamil reduced the platelet-activating factor-induced loss of neutrophil deformation, which was assessed by filtrometry (IC50 = 4.3 x 10(-6) mol/L). The effect of gallopamil was assessed in 24 patients during elective balloon angioplasty. Gallopamil (0.4 mg) or placebo (double-blind conditions) was administered by intracoronary application during the 10-min interval between the first two balloon inflations. In the placebo group, blood samples obtained simultaneously from the coronary sinus and from the femoral artery revealed an increase in the proportion of activated neutrophils in the coronary sinus blood after the second balloon inflation [nitro blue tetrazolium (NBT) score, NBT test: 15 +/- 9% relative coronary sinus and arterial blood difference, p < 0.05]; these changes in NBT score were similar to those after the first balloon inflation. In the gallopamil-treated group, however, significant arterial and coronary sinus blood differences in NBT scores were not found after the second balloon inflation. Gallopamil may, thus, attenuate the local neutrophil activation during balloon angioplasty. PMID- 1284154 TI - Abnormal coronary vasomotion in ischemic heart disease. AB - Myocardial ischemia has long been thought to be caused by only critical arteriosclerotic plaques, which are the most obvious single denominators of ischemic cardiac syndromes. The author argues that just because other transient and dynamic mechanisms are more elusive than atherosclerotic plaques, we should not presume them to be unimportant. He reviews the work of his group and others, which suggests that dilation and constriction can occur at the site of coronary artery stenoses and in distal coronary vessels. Clinical and angiographic findings and the possible pathophysiological causes of vasomotor dysfunction that may modulate residual coronary flow in patients with chronic stable, unstable, and variant angina, and syndrome X are reviewed. Only when these mechanisms are more fully understood will it be possible to develop specific therapy. PMID- 1284155 TI - Intracoronary gallopamil during percutaneous transluminal coronary angioplasty. AB - The present study was designed to investigate the effect of the calcium-channel antagonist gallopamil on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). Twenty-four adult patients with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) were randomly assigned to receive gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralization of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease, or renal failure were excluded from the study. PTCA was performed with use of at least two balloon inflations, each of 2 min in duration. Gallopamil (0.4 mg) or placebo (0.9% sodium chloride) was administered during the 10-min interval between the two inflations. For determination of myocardial lactate and hypoxanthine release, blood samples were taken simultaneously from the great cardiac vein and the femoral artery before and immediately after each inflation. Electrocardiogram changes were analyzed by measuring ST-segment deviations (80 ms after the J point) and maximal T-wave deviations of the leads I, II, III, and V2, V4, and V6. The most sensitive leads for identification of myocardial ischemia in the LAD area were V2 and V4. If compared to the first balloon inflation, the degree of ST-segment/T-wave changes induced by the second inflation was significantly reduced only in the presence of gallopamil. Furthermore, if compared to placebo, ischemia-induced lactate and hypoxanthine release was decreased in the presence of gallopamil. These results suggest that intracoronary application of gallopamil attenuates myocardial ischemia during PTCA. PMID- 1284156 TI - Reduction of myocardial ischemia by gallopamil: a dual-isotope study with thallium-201 and iodine-123 phenylpentadecanoic acid. AB - The present study was performed for characterizing the effect of chronic oral treatment with the calcium antagonist gallopamil on regional myocardial perfusion and free fatty acid utilization in poststenotic human myocardium. Twenty-two patients with angiographically documented coronary artery disease and stable angina pectoris underwent consecutive dual-isotope studies following simultaneous injection of 80 MBq thallium-201 and 200 MBq iodine-123 phenylpentadecanoic acid (IPPA) during a symptom-limited stress test. Radionuclide studies were performed after 1 week of placebo treatment (baseline), 4 weeks after oral treatment with 50 mg of gallopamil t.i.d. and again after 1 week of double-blind treatment with gallopamil or placebo. As compared to baseline, initial (poststress) uptake of both tracers in poststenotic myocardial segments was significantly improved after 4 weeks of treatment with gallopamil [thallium-201, +9.0%; p < 0.001; 95% confidence interval (CI), 4.3-13.6%; IPPA, +11.8%; p = 0.003; 95% CI, 4.2-19.3%]. Poststenotic IPPA-clearance was likewise significantly increased (+28.2%; p < 0.001; 95% CI, 12.4-44.0%) indicating a considerably enhanced myocardial fatty acid oxidation after treatment. In the final double-blind phase, myocardial uptake of both tracers as well as IPPA clearance remained enhanced in the subgroup of patients receiving gallopamil and returned to baseline values in patients receiving placebo. Thus, in poststenotic myocardium, chronic treatment with gallopamil provokes an improvement of both regional myocardial perfusion (as demonstrated by an increased tracer uptake in poststress scintigrams) and regional myocardial fatty acid utilization (as demonstrated by an increased uptake and clearance of IPPA). PMID- 1284157 TI - Diastolic ventricular dysfunction in noncomplicated acute myocardial infarction: the influence of gallopamil. AB - The goal of this study was to assess the effect of gallopamil on left ventricular (LV) diastolic function early after acute myocardial infarction (AMI). Gallopamil was compared with placebo and atenolol in two different groups of patients. Study patients, 2 days after experiencing their first AMI, in Killip class I and stable sinus rhythm, were randomized in a crossover, double-blind sequence to receive (a) gallopamil (50 micrograms/kg over 5 min) or placebo (i.v. 10-ml bolus, with a time interval of 90 min); and (b) gallopamil (50 micrograms/kg over 5 min) or atenolol (5 mg over 5 min), with a time interval of 24 h. Group I and group II consisted of 28 patients (26 men and 2 women; mean age 55 +/- 9 years) and of 14 patients (13 men and 1 woman; mean age 56 +/- 10 years), respectively. All the patients were treated with thrombolysis within 6 h from the onset of symptoms. Doppler echocardiographic examinations were performed as follows: at baseline (B) and 15 min after administration of gallopamil bolus and placebo bolus, in group I; at baseline before gallopamil (BG) and atenolol (BA), and 15 min after each bolus in group II. The following echo-Doppler parameters were calculated, at each examination: the early and late transmitral peak velocity ratio (E/A), the early and late velocity integral ratio (Ei/Ai), the peak filling rate normalized to mitral stroke volume (nMPFR), and the LV isovolumic relaxation time (IVRT), which was normalized to an 800-ms R-R cycle length in the patients in group II. Mean blood pressure (MBP) and heart rate (HR) were also measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284158 TI - Exercise-induced symptomatic and asymptomatic myocardial ischemia in patients with severe coronary artery disease: focus on the efficacy and safety of gallopamil. AB - Symptomatic and asymptomatic episodes of transient myocardial ischemia are well known risk factors in patients with coronary artery disease. In a single-blind, randomized, and placebo-controlled study, the efficacy and safety of gallopamil was studied during a 1-week treatment period in 25 patients with high-grade coronary artery stenosis and frequent, exercise-induced episodes of myocardial ischemia. Eighteen patients were men, and seven patients were women; the mean age +/- SD was 59 +/- 7 years. After a 1-week run-in period (days 1-7), all patients were treated with gallopamil 50 mg t.i.d. (days 8-14) and placebo t.i.d. (days 15 21) or vice versa. Twenty-four-hour Holter monitoring, exercise testing, and adverse effects were controlled at days 7, 14, and 21. During the run-in period, all patients suffered a mean of 5.9 +/- 2.9 episodes of transient myocardial ischemia, mean ischemic duration was 38 +/- 29 min/day. Gallopamil increased exercise tolerance from 7.9 to 9.8 min (+24%, p < 0.05) and resulted in reduction of the weekly usage of short-acting nitrates by 45% compared to placebo. During 24-h Holter monitoring, mean heart rate at the onset of ST-segment depression increased from 106 to 118 beats/min (p < 0.05). The frequency of daily ischemic episodes was reduced after gallopamil administration from 6.1 to 3.9 episodes/day (-37%, p < 0.05), the total ischemic burden decreased for symptomatic episodes by -54% (p < 0.05) and for asymptomatic episodes by 29% (p < 0.05). Gallopamil modified the circadian distribution of ischemic episodes by modifying the morning peak of transient myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284159 TI - Combined gallopamil and isosorbide-5-mononitrate in "mixed" angina pectoris. AB - The efficacy of combining gallopamil and isosorbide-5-mononitrate (IS-5-MN) was evaluated in 15 patients with "mixed" angina and documented coronary artery disease who participated in a 4-week, double-blind, double-dummy, crossover, placebo-controlled trial. After the first week of the placebo phase (single blinded), all patients received in three different weeks IS-5-MN 20 mg three times daily, gallopamil 50 mg three times daily, and the same dosages of IS-5-MN and gallopamil three times daily. Exercise tolerance, and peak values of heart rate, systolic blood pressure, double product (DP/100), and ST-segment were evaluated with a treadmill test at the end of each phase. The improvement in exercise tolerance obtained by the combination of the two drugs was significantly greater (p < 0.01) than that achieved by IS-5-MN but not that by gallopamil monotherapy (NS). This effect was accompanied by significant (p < 0.05) reduction (-61%) in ST-segment and significant (p < 0.05) increment (+8%) in peak heart rate only after administration of the combination of the two drugs. The number of ST-depression (ST-) > 1 mm or ST-elevation (ST+) episodes on 24-h Holter monitoring lasting > or = 1 min were also noted in all patients at the end of each phase of the trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284160 TI - Clinical evaluation of calcium-antagonist drugs. AB - Calcium-antagonist drugs are therapeutic agents of first choice in patients with coronary artery disease. We have reviewed a number of clinical trials in which the safety and efficacy of calcium blockers have been tested and discuss the established clinical effects of these compounds, which range from relief of angina and improved quality of life (both in patients with ischemia due to reduction in coronary flow and in patients with ischemia due to increased O2 demand) to a favorable effect on the course of coronary atherosclerosis and, finally, (at least for some of these agents) to an improvement in prognosis. PMID- 1284161 TI - Slow-release gallopamil in patients with stable effort angina. AB - Gallopamil (GSR) is a new calcium-channel blocker. The anti-ischemic activity of GSR was investigated in 12 patients with stable angina of effort, with fixed ischemic threshold (variations < 15%). After a 7-day washout period, patients were randomized to receive treatment with either GSR 100 mg or placebo twice daily for 7 days. Patients underwent maximal symptom-limited exercise test, 10 W/min on a bicycle, during washout (twice) and after the end of each treatment period. Patients were studied by electrocardiogram and the cuff method for determining systolic blood pressure. After treatment with GSR, ischemic and anginal thresholds were increased for at least 12 h in comparison with placebo (ischemic threshold: GSR 663 +/- 37, placebo 571 +/- 36, p < 0.01; anginal threshold: GSR 708 +/- 32, placebo 646 +/- 38, p < 0.05). Rate-pressure product was not changed at the same levels of exercise, but it was significantly increased during exercise at ischemic threshold. In conclusion, GSR possesses an anti-ischemic and antianginal activity lasting at least 12 h. This activity seems due to an increase of coronary blood flow to ischemic areas. PMID- 1284162 TI - Slow-release gallopamil evaluated by exercise test and long-term electrocardiography. AB - The effects of slow-release gallopamil (100 mg b.i.d.) were studied on exercise induced ST-segment depression as well as on spontaneous myocardial ischemia detected by long-term electrocardiography (ECG) monitoring for 48 h in 26 patients with coronary artery disease and angina pectoris. Eight patients had to be excluded (because of paroxysmal atrial fibrillation in four patients, development of unstable angina pectoris in three patients, and frequent ventricular premature beats in one patient). In the remaining 18 patients, gallopamil led to an increase of work load (W x min) evaluated by bicycle ergometry, paralleled by an increase of exercise duration until the occurrence of ST-segment depression of > or = 0.1 mV in the nonblinded part of the trial. The number of spontaneous episodes of myocardial ischemia during long-term ECG recording, ranging from 0 to 14 during control, decreased in patients with two or more episodes during control, paralleled by a decrease in the total duration of ischemic episodes and a decrease in the ischemic score (duration of episodes x maximal ST-segment depression). During long-term ECG monitoring, we observed asymptomatic episodes of spontaneous second degree atrioventricular block of the Wenckebach type in three patients. No other adverse effects of slow-release gallopamil were observed. Therefore, these preliminary results of the non-blinded protocol confirm the anti-ischemic effects of slow-release gallopamil given 100 mg b.i.d.; however, these promising results will have to be confirmed in the consecutive double-blind, placebo-controlled part of the trial. PMID- 1284163 TI - Efficacy and tolerability of slow-release gallopamil in patients with stable exercise-inducible angina pectoris. AB - The anti-ischemic properties and tolerability of a slow-release formulation (SR) of gallopamil were investigated in 118 patients with exercise-inducible ST segment depression and stable angina pectoris in this double-blind, randomized, placebo-controlled, multicenter study. After a placebo run-in period (A) of 2-7 days and a 7-day open therapy period (B) with gallopamil SR, the patients were randomized to a double-blind 7-day period (C) to receive placebo or gallopamil SR 100 mg twice a day. Each patient was submitted to gradual upright bicycle ergometry and electrocardiography (ECG) at rest on the last 2 days of each period at 6 and 12 h postadministration (p.a.) In period C, exercise time and exercise tolerance remained significantly prolonged at 6 and 12 h after gallopamil SR administration in comparison with the placebo values. Additionally the sum of ST segment depression and maximal ST-segment depression were significantly reduced by gallopamil SR at 6 h p.a. as were the frequency of angina attacks and nitroglycerin consumption. Four patients were withdrawn from the study because of gallopamil-related adverse events, which, however, were not serious. Constipation was noted in 2.5% of the patients. These data suggest that gallopamil SR is effective in reducing exercise-inducible ST-segment depression and increasing exercise tolerance with no serious adverse effects in patients with stable angina pectoris. PMID- 1284164 TI - Demonstration of specific neuronal cell groups in rat brain by beta-galactosidase enzyme histochemistry. AB - beta-Galactosidase activity as illuminated by the indigogenic X-gal staining method has been used to demonstrate the presence of genetically modified cells carrying the reporter gene lacZ, coding for the E. coli enzyme. Endogenous activity has been assumed to be minimal since the pH optimum for the mammalian enzyme is 3.5-5.5, while the pH optimum for the E. coli enzyme (and thus of the staining procedure usually employed) is 7.3. Background staining has been reported to be limited to pericytes and a few specific neuronal cell groups. In contrast, our investigations of normal rat brain anatomy demonstrate that many specific neuronal cell groups possess endogenous beta-galactosidase activity when staining is performed at physiological pH. This suggests that background staining of endogenous beta-galactosidase activity in the rat brain has been underestimated. In addition, such specific activity would afford an additional means of identification and illustration of these cells. PMID- 1284166 TI - HRP reacted with the chromogen o-tolidine produces whole-cell reaction product at light and electron microscope levels: negative effects of sucrose and Golgi staining on benzidine reactions. AB - Studies of pathway microcircuitry often require electron microscope analysis. To facilitate these analyses, methods for labeling cells in their entirety are extremely useful. Furthermore, such a method would be most useful if the label would be completely confined by the cell membrane so that second labels for synapse identification could be used. No existing method reliably and repeatably produces this kind of a result. In seeking to develop such a method, a seldom used chromogen for horseradish peroxidase (HRP) was found which produced superlative results for light and electron microscope analysis. o-Tolidine (3,3' dimethylbenzidine) reacted with HRP produces a very electron-dense reaction product distributed uniformly throughout the cytoplasm and nucleoplasm; membranes are unobscured so that mitochondria, lysosomes, Golgi apparati and endoplasmic reticula are well defined. The reaction product extends into cellular processes of all sizes, including processes with cell bodies not within the plane of section, and is easily visualized at even the lowest electron microscope magnification. The HRP reaction product is completely confined by the cell membrane, thus terminals presynaptic to labeled cells remain distinct. However, the o-tolidine/HRP reaction product is negatively affected by exposure to oxidizers. In tissue exposed to sucrose before or after being reacted with o tolidine, the HRP reaction product is less electron dense and is found only in lysosomes outside the nucleus or occasionally in proximal cellular processes. The o-tolidine/HRP reaction product is similarly affected when exposed to potassium dichromate for Golgi staining. For some other benzidine compounds, the chromogen/HRP reaction product is also negatively affected by exposure to these chemicals. Therefore, o-tolidine is a superior chromogen for HRP, labeling cells with details similar to that found for cells intracellularly injected with HRP. PMID- 1284165 TI - Voltammetric monitoring of brain extracellular levels of serotonin, 5 hydroxyindoleacetic acid and uric acid as assessed by simultaneous microdialysis. AB - We have previously developed a microcomputer-assisted curve-fitting method for measuring the components of the mixed electrochemical signals recorded by differential normal pulse voltammetry in the living brain. It was initially used for resolution of the dopamine and dihydroxyphenylacetic acid components of the catechol signal (peak 2). This report shows how it can be applied to analysis of the indoleamine/uric acid (UA) components of the more complex peak 3. The voltammogram is modeled as a mixture of 3 normal curves of known parameters corresponding to the oxidation of UA, 5-hydroxyindoleacetic acid and serotonin, which is solved by non-linear iterative procedures. Performance was assessed by treatments with drugs having well-known effects on the substances monitored, pargyline and allopurinol, and by the chromatographic analysis of microdialysates collected simultaneously from the contralateral side. PMID- 1284167 TI - Protective effect of zinc acexamate on experimental gastric ulcers: a histochemical study. AB - The antiulcerogenic effect of zinc acexamate on gastric ulcers induced by reserpine and changes in the morphology of gastric mucosa were studied in rats by histochemical methods. Histochemistry revealed that zinc acexamate preserved reserpine-depleted neutral and acid glycoproteins. ATPase reaction remained strong in nearly normal periglandular capillaries. The reaction intensity of SDH and NADH2-tetrazolium reductase, and the number and size of the DH-positive parietal cells were decreased, illustrating the decline of energy metabolism involved in acid secretion. The decreased height and weaker staining of the pyroninophile chief cell layer corresponded to the lower amount of RNA, an indirect indicator of pepsinogen synthesis. The significant correlation indices "r" between the severity of gastric lesions and histochemical parameters of the defensive (glycoproteins and microvascular ATPase) and aggressive factors (parietal cell DH and chief cell RNA) confirmed the pathogenic effect of reserpine and the protection provided by zinc acexamate. These findings confirm the multifactorial mechanism of action described for zinc acexamate in several previous works. PMID- 1284168 TI - Metaphor as illness: postmodern dilemmas in the representation of body, mind and disorder. AB - The search for a synthesis bridging the gap between materialist and idealist approaches in anthropological theory has been invigorated by recent efforts to develop a critical medical anthropology. Not limited to integrating class analysis and cultural interpretation, the "mindful body" paradigm also aims at empowering the ill, whose experience is denied by biomedical and psychiatric categories that locate disease either in the body or in the mind, and treat them separately from one another and independently of social context. However, missing from the "mindful body" discourse is a reflexive awareness of its contextual grounding in both popular and biomedical discourses of illness, with which it exchanges meanings and from which it borrows dominating power. The case of cancer as a metaphorized illness and a pathologized trope is used to illustrate this process. PMID- 1284169 TI - Medical anthropology and the depths of human experience: contributions from psychoanalytic anthropology. PMID- 1284170 TI - The effect of aflatoxin B1 exposure on serotonin metabolism: response to a tryptophan load. AB - Semi-chronic exposure of ICR male Mice to Aflatoxin B1 (AFB1) in non-toxic doses decreased brain serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) and catecholamines without altering tryptophan (TRP) or tyrosine (TYR) levels. A TRP load (300 mg/kg, i.p. x 2 hours) slightly increased brain TRP levels while causing a slight decrease in 5-HT and 5-HIAA in control animals. A TRP load in AFB1 treated mice increased brain 5-HT and 5-HIAA. The TRP load caused a further reduction in brain catecholamines without altering TYR levels. Exposure to AFB significantly increased lung TRP levels without altering 5-HT or 5HIAA levels. TRP loading increased lung TRP concentrations in control mice. However, in AFB1 treated mice the increase was not significantly elevated above the level caused by AFB1 treatment alone. Lung 5-HT or 5-HIAA levels in control or AFB1 treated mice are not significantly altered by TRP loading. These experiments demonstrate that AFB1 alters brain and lung TRP metabolism. PMID- 1284171 TI - Effect of vitamin C administration in modulating some biochemical changes in arthritic rats. AB - Two phases of arthritis, acute phase (four days after adjuvant inoculation) and chronic phase (21 or 29 days after adjuvant inoculation) were studied in male rats. The effect of administration of vitamin C in a daily oral dose of 50 mg/kg body wt for four and 21 days starting on the day of adjuvant inoculation and for 7 days starting 21 days after adjuvant inoculation against these phases of arthritis was demonstrated. Results showed that prolonged administration of vitamin C (21 days) increased the lowered serum sulphydryl (SH-groups) to prearthritic values while it decreased the elevated level of blood glutathione (GSH) of arthritic rats. However, neither (four-day) nor seven-day treatment with vitamin C exerted any significant changes in these parameters. The results showed also a slight significant increase in the level of erythrocyte superoxide dismutase activity (SOD) [1.15.1.1] upon seven-day treatment with vitamin C. Meanwhile, four-, 21- or seven-day treatment with vitamin C produced no significant change in the elevated levels of serum ceruloplasmin (Cp) and alpha 2 macroglobulin (alpha 2-M) of arthritic rats. However, 21-day and 7-day administration of vitamin C has improved the lowered A/G ratio in these animals. The improvement in these parameters after prolonged administration of vitamin C was explained in the light of the antioxidant property of this vitamin and suggests a beneficial role for it in the treatment of arthritis. PMID- 1284172 TI - [Adhesion of lymphocytes to allogenic endothelium. Four different pathways]. AB - Lymphocyte adhesion to allogeneic endothelium is a critical step in graft rejection. To further characterize the expression and the regulation of adhesion molecules involved in this process, we stimulated endothelial cells with Interleukin 4 or tumor necrosis factor alpha (TNF alpha) and blocked lymphocyte adhesion to stimulated-endothelial cells with monoclonal antibodies. We demonstrated that lymphocytes bound endothelial cells by at least four adhesion pathways: a) a LFA 1/ICAM 1 dependent pathway on TNF alpha-stimulated endothelial cells, b) a LFA 1 dependent/ICAM 1 independent pathway on unstimulated or IL 4 stimulated endothelial cells, c) a VLA 4/VCAM 1 dependent pathway on unstimulated and stimulated-endothelial cells, d) a CD 2 dependent/LFA 3 independent pathway on IL 4 and TNF alpha-stimulated endothelial cells. PMID- 1284173 TI - [T CD57+ lymphocytes in kidney transplanted patients. Phenotypic and functional study]. AB - Phenotypic analysis showed a significant increase of CD3+/CD57+ lymphocyte subpopulation in 88 kidney-transplanted patients when compared with non transplanted patients. No clear correlation was found between the increase of this cell subpopulation and renal function, immunosuppressive regimen, and allogenic or viral stimuli, when each of these factors was considered. Conversely, there was a significant correlation between the proportion of CD3+/CD4+/CD57+ cells and the post-transplant follow-up period. Finally, functional study of CD3+/CD57+ cells suggested that they have suppressive properties, in vitro. PMID- 1284174 TI - [Amplification of a circulating CD4+CD7- T lymphocytes subset in kidney transplantation]. AB - A minor subset of CD4+ T-cells (10 +/- 4 percent) that does not express the CD7 antigen is detectable in normal individuals. These CD4+CD7- T-cells have lower proliferative capacities than autologous CD4+CD7- T-cells. We observed an expansion of CD4+CD7- peripheral T-cells in 45 kidney transplant recipients. The CD4+CD7- TL expansion (23 +/- 20 percent was observed in both short term (< 6 months, n = 20) and long term transplanted patients (> 3 years, n = 25). These results significantly differed from those observed in patients on dialysis (10 +/ 4 percent, P < 0.002). The percentages of CD4+CD7- TL in kidney recipients are significantly correlated with the percentages of CD4+CD57+ and CD8+CD57+ T-cells subsets. A three-color immunofluorescence analysis indicated that 75 percent of the CD4+CD7- TL express the CD57 molecule contrasting with those in normal individuals (0.3 percent). Purified CD4+CD7- T-cells from kidney recipients have lower proliferative responses after PHA, CD2 and CD3 stimulations than autologous CD4+CD7+ TL. The proliferative response is partially restored by the addition of anti-CD28 moAb or IL2. We have highlighted, in kidney recipients with good graft function, an expansion of CD4+CD7- T lymphocytes which could be associated with CD4+ T-cell anergy and tolerance. PMID- 1284175 TI - [A proposal of the essential elements for teaching the process of nursing care and its application to the surgical patient]. AB - Greater dynamism is advocated in the teaching-learning process of Nursing Care by proposing essential skills which are both logical and specific, necessary and sufficient, to provide people (healthy or diseased), the family and the community with more efficient and quicker nursing cares. The theoretical foundations of the invariants proposed are stated and a description is given of the operational method for evaluating students' case discussions by using a measuring scale in a surgical patient with hydric, electrolytical and acid-basic unbalance. The results reached are satisfactory since 50% of the students were evaluated as "very high". Continuation of the study with other groups of students is recommended. PMID- 1284176 TI - [Changes in the blood glucose of revascularized patients in the immediate postoperative period]. AB - Variability in glycaemia in revascularized patients in the immediate postoperative period was studied in order to determine the presence of hyperosmolar hyperglycaemia coma, ketogenic and non-ketogenic, and the relation with hemodynamic changes. It was found that 15 patients (9.2%) from the Arteriology Service and two patients (7.1%) from the Diabetes Angiopathy Service had a non-ketogenic hyperglycaemic hyperosmolar coma and there was no ketogenic hyperglycaemic hyperosmolar coma. There were 32 patients (16.8%) with hemodynamic changes who had mild and moderate hyperglycaemia in the immediate postoperative period. PMID- 1284177 TI - Effect of benzodiazepines on tryptophan binding to rat hepatic nuclei. AB - This study evaluates whether or not some of the benzodiazepines would influence the binding of L-tryptophan to rat hepatic nuclei or nuclear envelopes. Previous publications have indicated that binding of L-tryptophan to hepatic nuclear envelope proteins was saturable, stereospecific, and of high affinity. In this study, we investigated whether some of the benzodiazepines would influence L tryptophan binding to rat hepatic nuclei or nuclear envelopes as assayed by in vitro L-(5-3H) tryptophan binding. Our results indicate that the addition of chlordiazepoxide, diazepam, prazepam, flurazepam, nordazepam, N desalkylflurazepam, temazepam, oxazepam, lorazepam, or 4-chlorodiazepam has little influence on the L-(5-3H) tryptophan binding to hepatic nuclei in vitro. However, the addition of demoxepam, the N-desalkylated compound of chlordiazepoxide, caused marked competition with 3H-tryptophan binding to hepatic nuclei in vitro. When chlordiazepoxide (1 mg/100 g body weight) is administered intraperitoneally 20 min before killing, the isolated hepatic nuclei reveal decreased specific L-tryptophan binding compared to controls. Also, rats pretreated with chlordiazepoxide intraperitoneally before tube-feeding L tryptophan revealed diminished tryptophan-induced hepatic nuclear RNA efflux and protein synthesis. Our results suggest that chlordiazepoxide, possibly by itself or through a metabolite, can act to affect hepatic nuclear binding of L tryptophan and to inhibit the stimulatory effect of L-tryptophan on hepatic protein synthesis. PMID- 1284178 TI - N-nitrosoheptamethyleneimine-induced pulmonary and esophageal carcinogenesis and effects of concomitant treatment with bleomycin in rats. AB - The combination effects of bleomycin with N-nitrosoheptamethyleneimine (NHMI) or dihydroxy-di-N-propylnitrosamine (DHPN) on pulmonary carcinogenesis were investigated. Male F344 rats were given NHMI (20 or 40 ppm) or DHPN (200 ppm) in the drinking water and intraperitoneally injected with bleomycin (1 mg/kg) once a week for 18 weeks and then killed at week 24. Many rats treated with NHMI died before the termination of the experiment due to toxicity or development of advanced esophageal carcinomas, considered to be the main cause of death. Detailed histological examination performed on rats killed at week 24 revealed no statistically significant effects of bleomycin on NHMI or DHPN induction of neoplastic lesions in the lung or esophagus, although pulmonary carcinomas were only found in two rats treated with NHMI plus bleomycin. Under the present experimental conditions, NHMI exerted stronger carcinogenic activity in the esophagus than in the lung, and no obvious modifying effects of simultaneously administered bleomycin were evident on NHMI- or DHPN-induced pulmonary carcinogenesis. PMID- 1284179 TI - Severe cutaneous hypersensitivity reactions during treatment of tuberculosis in patients with HIV infection in Tanzania. AB - Concurrent infection with HIV-1 and Mycobacterium tuberculosis is increasingly common in East Africa. In the past, a drug regimen consisting of 2 months of intramuscular streptomycin plus 12 months of isoniazid and thiacetazone has been used in tuberculosis control programs with acceptable efficacy and low incidence of adverse reactions. Anecdotal reports of increasing cases of Stevens-Johnson syndrome prompted a 2 month prospective search for cases of severe cutaneous hypersensitivity reactions at Muhimbili Medical Centre in Dar es Salaam, Tanzania. Five such patients were admitted to a single ward during this time, 4 of whom were HIV-seropositive and all of whom were being treated with isoniazid and thiacetazone. These findings have implications for the management of tuberculosis in East Africa and perhaps other countries with high prevalence of both HIV-1 and tuberculosis. PMID- 1284180 TI - [Congenital hepatoblastoma: a case report]. PMID- 1284181 TI - [The mapping of the neurons that participate in the innervation of the body wall of the edible snail]. AB - In the paper are presented the results of the experiments with the retrograde staining of the left-side cutaneous nerves of the pedal ganglia of the snail Helix lucorum. The somata of neurons which sent processes forming the studied nerves were revealed with the help of nickel and cobalt ions precipitation by the rubeanic acid. A lot of nerve cells including some command neurons were found in all the ganglia excluding the buccal ones. Especially large amount of neurons was stained in the ipsilateral pedal, pleural, and parietal ganglia. PMID- 1284182 TI - [New identified nerve cells in the edible snail Helix pomatia related to the generation of pacemaker activity]. PMID- 1284183 TI - [The structural organization of the snail sensory systems]. AB - In the paper are reviewed the author's data on the structure of peripheral nervous system of the body wall, gravitational organs--statocysts, eyes, and organs of distant chemoreception--ommatophors, or posterior head tentacles, of the snails Helix vulgaris and Helix pomatia. Localization in the CNS of central parts of the main sensory systems is shown and some structural characteristics of them are described. The data on the organization of the procerebrum which takes part in processing of information from the receptors of the head tentacles are presented. By some morphological features the procerebrum may be considered as one of the highest associative centers of the snails. The data under consideration were obtained by means of silver impregnation by Golgi, retro- and anterograde infusion of CoCl2, horseradish peroxidase and Lucifer yellow into the nerves, as well as by means of a number of other classical histological techniques. PMID- 1284184 TI - [The facilitation of defensive reactions during food consumption in the snail helix: the participation of glucose and gastrin/cholecystokinin-like peptide]. AB - Molecular and cellular mechanisms of the interrelations between the feeding and defense behaviour were studied in a snail Helix lucorum. The dynamics of defense reactions was investigated in snails with different levels of feeding motivation. Defense reactions were suppressed in hungry snails, while 15-20 min after the beginning of food intake they were facilitated. The facilitation depended on a duration of starvation. Injection of 0.5 ml of 5 mM glucose solution (up to the glucose level in the haemolymph of a food satiated snail, 1.6-2.0 mM) or injections of 20-30 ng of synthetic analogues of the gastrointestinal peptides (pentagastrin of octapeptide cholecystokinin, CCK-8) facilitated the defense reaction in a hungry snail. Parameters of the facilitation were similar to those in the period of food intake. Activity of the command neurons of defense behaviour (L-PPL1) after the carrot juice application to the lip of a semi-intact preparation from a hungry snail was glucose-dependent. Similar glucose-dependent changes of L-PPL1 activity were found after CCK-8, but not FMRFamide application during the perfusion with 0.5 mM glucose. L-PPL1, but not L-PPa2-3 neurons were most sensitive to glucose and CCK-8 level changes in the Ringer solution. Adaptive significance of the behavioural phenomena as well as glucose and gastrin/CCK-like peptide participation in these processes are discussed. PMID- 1284185 TI - [The cholinoreceptors of the neurons in the edible snail: their identification and plasticity and its regulation by opioids and second messengers]. AB - In the paper is presented the review of author's own data on the cholinoreceptors of identified Helix neurons and the regulation of their plasticity. The review contains the following parts: cholinoreceptors identification, their coupling with ionic channels, identification of opioid receptors, modulation of cholinoreceptors by opioids, plasticity of cholinoreceptors, modulation of their plasticity by the second messengers, second messengers involved in a modulation of cholinoreceptors' plasticity by the opiate kappa-agonist bremazocine. PMID- 1284186 TI - Erythrocytes as carriers of ricin A chain: effects on the erythrophagocytic cells. PMID- 1284187 TI - Use of fluorescent probes for describing the process of encapsulation by hypotonic dialysis. PMID- 1284188 TI - Induction of mucosal and serum immune responses to a specific antigen of periodontal bacteria. AB - The dynamics of the host immune response to periodontal bacteria not only may be informative from the standpoint of specific mucosal protection to these pathogens, but also may reveal the capacity of the mucosal immune response to provide protection of the host. To this end, we have examined the immune response to chromatographically purified fimbriae of P. gingivalis administered orally or systemically with liposomes and adjuvant in BALB/c mice, high responders to this antigen. Oral administration of P. gingivalis fimbriae clearly enhanced the fimbriae-specific salivary IgA response. ELISPOT analysis revealed that significant numbers of fimbriae-specific IgA SFC were seen in lamina propria and mesenteric lymph nodes but not in Peyer's patches of mice immunized orally. In contrast, antigen-specific IgM and IgG SFC were seen mainly in the circulating blood mononuclear cells. On the other hand, subcutaneous injection of fimbriae with GM-53 also raised the fimbriae-specific IgG followed by IgM and IgA responses in serum, and both IgA and IgG responses in saliva. Oral immunization was less effective than subcutaneous injection in terms of the serum antibody response. However, the salivary antibody level of mice injected subcutaneously was similar to that of mice immunized orally. In the subcutaneously immunized mice, fimbriae-specific SFC were detected in the spleen, blood, and brachial lymph nodes by ELISPOT assay. Fimbriae-specific IgM SFC appeared earlier and antigen-specific IgG SFC were seen later. These results show that the combined use of fimbriae together with the adjuvant results in sharply increased IgA responses in saliva and IgG responses in serum. In summary, it is clear that the nature of the host's antibody response in serum and mucosal secretions is distinct, and depends on the route of antigen administration, the use of adjuvant and/or liposomes, and the temporal phase of the humoral immune response following various immunization regimes. PMID- 1284189 TI - Canatoxin triggers histamine secretion from rat peritoneal mast cells. AB - Canatoxin, a toxic protein present in the seeds of Canavalia ensiformis, induces the secretion of serotonin, dopamine and insulin through activation of the lipoxygenase pathway. The purpose of the present study was to verify if canatoxin causes histamine release from rat peritoneal mast cells and to perform a detailed study of this phenomenon. Our results indicate that canatoxin is capable of activating mast cells to release histamine. The process is time- and concentration-dependent, occurs without cell damage and requires metabolic energy as well as the presence of divalent cations (Ca2+ and Mg2+). Optimal release occurs at 37 degrees C and at physiological pH. Extremes of temperature (0 degree C and 45 degrees C) inhibit the process. We conclude that canatoxin induces histamine release from rat peritoneal mast cells by an active secretory process. PMID- 1284191 TI - Substance P as a potent stimulator of sneeze responses in experimental allergic rhinitis of guinea pigs. AB - Substance P was examined for sneeze-inducing activity and its involvement of sneeze responses in experimental allergic rhinitis. Substance P, dripped into a nostril of guinea pigs, at concentrations of 100 pM and above induced sneezing in a dose-dependent fashion. The activity of substance P was not affected by the previous subcutaneous injections of capsaicin that depleted substance P in nerve fibers. Histamine induced sneezing at concentrations of 30 mM and above and the activity was reduced by capsaicin treatment. The frequency of antigen-induced sneezing was proportional to the substance P content in nasal mucosa of sensitized guinea pigs treated with increasing doses of capsaicin; correlation coefficient 0.91. These results suggest that substance P plays an important role as a stimulator of sneeze responses in experimental allergic rhinitis in guinea pigs. PMID- 1284190 TI - The effects of histamine, pyrilamine, cimetidine, and ranitidine on secretion of lingual lipase and amylase from rat von Ebner's glands. AB - Minced von Ebner's glands of rat tongue were incubated in vitro with histamine and histamine receptor antagonists. At various time intervals, media and homogenates of the tissue were assayed for lingual lipase and amylase activity and percentage secretion calculated. Histamine elicited moderate secretion (approximately 10%) of lingual lipase and amylase. In contrast, pyrilamine, an H1 receptor antagonist, elicited > 60% secretion. There were statistically significant differences between the percentage secretion of lingual lipase and amylase for basal secretion, as well as for histamine- and pyrilamine-evoked secretion above basal. The H2 receptor inhibitors, cimetidine and ranitidine, stimulated secretion of only amylase, but not lingual lipase. When combined with histamine, these antagonists partially inhibited only the secretion of histamine evoked lingual lipase, but not amylase. The differences in percentage secretion between the two enzymes indicate that exocytosis may not be the only process involved in protein secretion. The anomalous effects of the H1 and H2 receptor antagonists necessitate a more detailed characterization of the receptors of von Ebner's glands. PMID- 1284192 TI - Suppressive effects of E3330, a novel quinone derivative, on tumor necrosis factor-alpha generation from monocytes and macrophages. AB - E3330 [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid], a novel synthesized hepatoprotective compound, has suppressive effects on tumor necrosis factor-alpha (TNF-alpha) generation from monocytes/macrophages in vitro. E3330 (1-100 microM) reduced lipopolysaccharide (LPS, 10 mg/ml or 1 microgram/ml)-induced TNF-alpha generation from rat resident and Propionibacterium acnes (P. acnes)-elicited peritoneal macrophages, rat and human monocytes, rat Kupffer cells, and splenic mononuclear cells in a concentration dependent manner. E3330 also (1-100 microM) suppressed TNF-alpha generation stimulated with egg-albumin immune complex in rat P. acnes-elicited peritoneal macrophages. Northern blot analysis showed that LPS-induced expression of TNF alpha messenger RNA (mRNA) in human blood monocytes was suppressed by E3330. These findings indicate that E3330 has a suppressive effect on TNF-alpha generation from monocytes/macrophages, regardless of origin or species, and this effect is based in part on the suppression of TNF-alpha mRNA expression. PMID- 1284193 TI - Thermodynamic theory of active membranes. PMID- 1284194 TI - Knowledge about developmental screening in mothers attending a maternal and child health clinic in Singapore. AB - A study of knowledge about Developmental Screening in mothers was done among 200 Singapore mothers attending a Maternal and Child Health Clinic from February to March 1990. They were requested to answer a set of questions pertaining to their knowledge on the Developmental Screening session and their reason for attending the session. They were also asked whether they had attended any health education talks given by the nurses in the clinic. Seventy-three out of 200 (36.9%) knew what the appointment given was for. Mothers with secondary education were almost three times and mothers with tertiary education were five-and-a-half times more likely to possess the correct knowledge than a mother with primary education. Wives of husbands from Social Classes I and II were more knowledgeable (83% and 54%) than those in lower social classes (32% and 25%). Mothers with older children were more knowledgeable than those with children age six weeks. Mothers of one child four-and-a-half years old were more knowledgeable than those with one child age six weeks. Twelve out of 27 (44%) of mothers of one child age six weeks did not know what Developmental Screening was about whereas all mothers with four-and-a-half year old children knew what Developmental Screening was about. Only 88 (44%) mothers had attended health education talks. There was no discernible difference in knowledge of Developmental Screening between those mothers who attended talks and those who did not (35% vs 40%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284195 TI - Renal tubular function of cadmium exposed workers. AB - The kidney is considered the critical organ following long term occupational or environmental exposure to cadmium. Tubular dysfunction in the form of low molecular weight proteinuria is the earliest manifestation of cadmium nephrotoxicity. The current acceptable critical concentration of cadmium in the urine is 10 ug Cd/g creatinine. The aim of this paper is to identify the presence of tubular dysfunction among workers with less than 10 ug Cd/g creatinine. The exposed group of 92 workers were from a nickel-cadmium battery factory. The control group of 122 workers were factory and sedentary office workers with no known history of exposure to nephrotoxic agents. The urinary excretion of N acetyl-D-glucosaminidase (NAG), beta-2-microglobulin (beta 2m) and alpha-1 microglobulins (alpha 1m) were measured from morning spot urine samples. The age, sex and race adjusted NAG and alpha 1m showed increasing trend with rising urinary cadmium levels. Levels were significantly raised when the urinary cadmium was above 5 ug Cd/g creatinine. A similar trend was seen with increasing length of exposure. Renal tubular dysfunction is present among cadmium exposed workers with levels below the current critical concentration. PMID- 1284196 TI - Vimentin expression in benign and malignant lesions in the human mammary gland. AB - The distribution pattern of vimentin in mammary gland lesions, including benign lesions (36 cases) and adenocarcinomas (40 cases), was studied with the use of a monoclonal antibody. In myoepithelial cells of mastopathy, the positive vimentin staining was seen in 6 cases (33.3%). Gynecomastia showed strong vimentin expression in myoepithelial cells. Fibroadenomas (14 cases) expressed positive vimentin staining in 8 cases (57.1%) with various staining intensities in myoepithelial cells. Lactating mammary gland tissue was positive for vimentin staining in narrow myoepithelium. In adenocarcinoma, positive reactions in tumor cells were found in 17 cases (41.2%) of solid tubular, 12 cases (33.3%) of papillo-tubular, and 11 cases (54.5%) of scirrhous carcinomas. The staining intensity for vimentin was weak in modified myoepithelial cells and neoplastic cells. Malignant cells in mammary carcinomas with vimentin reactivity usually expressed keratin staining; thus a co-expression of vimentin and keratin was found in mammary carcinomas. PMID- 1284197 TI - Enhancement by androgen of the angiogenic ability of androgen-responsive Shionogi carcinoma 115. AB - The effects of various steroids on the induction of angiogenesis by androgen responsive Shionogi carcinoma 115 (SC115) were investigated by implanting a piece of a SC115 tumor tissue into a rabbit cornea together with a pellet containing each steroid (250 micrograms) and by examining neovascularization from the limbus. SC115 tumor tissues induced neovascularization in 42% corneas in the absence of steroids, and in 31, 63, 80 and 4% in the presence of estradiol-17 beta, progesterone, testosterone and dexamethasone, respectively. Only testosterone significantly increased the percentage of corneas with neovascularization, while dexamethasone significantly decreased it. Testosterone itself induced no neovascularization, and dexamethasone also inhibited neovascularization induced by acidic fibroblast growth factor. The present results suggest that androgen increases the secretion of an angiogenic factor(s) by an androgen-responsive SC115 tumor, while dexamethasone inhibits angiogenesis induced by the angiogenic factor(s). PMID- 1284198 TI - Immunohistochemistry in stage FIGO III cervical cancer: prognostic value of tumor associated antigens and intermediate filaments. AB - The prediction of prognosis in cervical carcinomas solely by histological examination is doubtful. Our study was undertaken to evaluate whether Cytokeratin 5D3, Cytokeratin high molecular weight (HMW), Cytokeratin AE1/AE3, Carcinoembryonic Antigen (CEA) and CA 19.9 could have a prognostic value in primarily irradiated stage FIGO III cervical cancer. We investigated 45 pretreatment punch biopsies of cervical cancer stage FIGO III. All patients underwent a combined standardised primary irradiation treatment. In the cases with expression of Cytokeratin AE1/AE3 survival was significantly better than in cases without expression. The expression of CEA also had a significantly positive effect on survival. The best prognosis was found in cases with coexpression of AE1/AE3 and CEA (Wilcoxon p = 0.006, log-Rank p = 0.03). The other investigated tumor associated antigen and intermediate filaments did not correlate with survival. The application of Cytokeratin AE1/AE3 and CEA allows a prediction of prognosis in patients with stage FIGO III cervical cancer undergoing irradiation treatment. PMID- 1284199 TI - Squamous cell carcinomas, an immunohistochemical and ultrastructural study. AB - Fourty-seven squamous cell carcinomas (SCCs) were studied by light microscopy, immunohistochemistry and electronmicroscopy. Nineteen percent (9 cases) of SCCs in different locations were immunoreactive for CAM5.2 and three poorly differentiated SCCs did not express cytokeratins 6 and 18. No cases were positive for c-erbB2 protein. p53 protein overexpression was found in malignant cells in 40% of the primary tumours and in 60% of the lymph node metastases. Four poorly differentiated SCCs expressed vimentin and in these cases the tumour cells had accumulations of less dense intermediate filaments in cytoplasm. PMID- 1284200 TI - Partial characterization of protein tyrosine kinases in human lymphoid cells. AB - We have examined several aspects of protein tyrosine kinase (PTK)-activity in the cytosolic and membrane fractions of both normal and malignant lymphoid cells. The expression of the PTK-encoding oncogenes fes, abl and src, was investigated with the use of antibodies generated to their respective gene products. These antibodies recognized proteins in all cell types examined, most frequently in both the cytosolic and the membrane fraction. PTKs were partially characterized by FPLC. PTK-activities of column fractions were assayed using a non-radioactive dot blot assay. Cytosolic and membrane fractions showed FPLC patterns with a constant as well as a variable part in both normal and malignant cells, suggestive of PTKs with specialized functions in normal cell growth and transformation. Lastly, using antibodies to phosphotyrosine, we found that cytosolic fractions contained the majority of proteins phosphorylated at tyrosine in all cell types. Normal peripheral blood lymphocytes and B-lymphoma cells showed a great similarity in tyrosine phosphorylation pattern, while in tonsillar lymphocytes a clearly different pattern was found. These methods further characterize PTK-activities in lymphoid cells, and the results give evidence that PTKs in normal and malignant cells have both similar and different aspects. PMID- 1284201 TI - Chemosensitivity testing of xenografted squamous cell carcinomas of the head and neck region. AB - Eight squamous cell carcinomas from the head and neck region were established as xenograft lines in nude mice and tested for their sensitivity to the antineoplastic drugs bleomycin and cisplatin. Tumor volume, histology, DNA flow cytometry and mitotic activity were used as parameters. One out of the 8 tumours appeared to be highly sensitive to bleomycin, while three other tumours were sensitive to both bleomycin and cisplatin. These observations are in good correlation with the reported data in patients. All chemosensitive tumours showed regrowth after the cytotoxic drug treatment had been completed. No change was seen in the chemosensitivity of other features of the regrown tumours, not even after repeated exposure to the drugs. Comparison of the tumour volume with the other parameters applied indicated that the tumour volume of squamous cell carcinomas was not always a reliable parameter for testing chemosensitivity, because of the important contribution of keratin to the tumour volume. It is concluded that additional parameters such as histological examination, DNA flow cytometry or mitotic activity are necessary in order to draw reliable conclusion on xenografts with a large avital component. In addition, DNA flow cytometry has proved to be very useful for the rapid screening of drug sensitivity. PMID- 1284202 TI - MDR hamster cells exhibiting multiple altered gene expression: effects of dexniguldipine-HCl (B859-35), cyclosporin A and buthionine sulfoximine. AB - An actinomycin D selected, multidrug-resistant (MDR) hamster CHO subline showed strong expression of the P-glycoprotein and sorcin genes together with several other alterations such as a: (i) reduced growth rate, (ii) lowered topoisomerase II, (iii) lowered glutathione-S-transferase-P gene expression, and (iv) the emergence of a 15.5 kDa protein. Besides high resistances to adriamycin, actinomycin D, and vincristine, we observed a lowered sensitivity towards bleomycin, a rather hydrophilic drug usually not involved in P-glycoprotein associated MDR. Moreover, the MDR subline showed a pronounced collateral (enhanced) sensitivity towards the sterically pure dihydropyridine anticancer drug dexniguldipine-HCl (B859-35) preventing its characterization for MDR modulation here. At a non-cytotoxic dose (10 microM) the immunosuppressive cyclic peptide cyclosporin A completely abolished the resistance to vincristine, partially reversed the resistance to teniposide and strongly enhanced the sensitivity towards bleomycin, while not influencing the drug sensitivities of the parental cell line. Buthionine sulfoximine (BSO), an agent depleting cellular glutathione levels, distinctly increased the sensitivity towards teniposide at nontoxic doses (50 microM) exclusively in the MDR subline, while it did not alter vincristine or bleomycin cytotoxicity. PMID- 1284204 TI - Medial canthal keratinisation (MCK): a diagnostic sign of ocular cicatricial pemphigoid. PMID- 1284203 TI - Morphology and intermediate filament composition of human mammary epithelial cells treated with stable butyrate derivative. AB - A new stable butyrate derivative monobut-3 was previously shown to inhibit proliferation and promote differentiation in human mammary established cell lines. The present study on monobut-3's effects on mammary epithelial cells cultured from human non-malignant and malignant breast tissues demonstrated pronounced morphological alterations suggestive of cellular differentiation. In addition, some degree of architectural differentiation was also evident in treated primary cultures. Monobut-3 did not affect the expression of vimentin and cytokeratin 18 when assessed in human breast cell lines expressing one or both types of intermediate filaments. However, it did induce expression of cytokeratin 19, characteristic of fully differentiated mammary cells, in one of the two cell lines devoid of this cytokeratin subtype. Furthermore, the network of intermediate filaments was often more largely extended in cells treated with monobut-3 than in untreated ones. These results indicate that monobut-3 can induce subtle changes in intermediate filaments which may contribute to its ability to promote differentiation in human mammary cells. PMID- 1284205 TI - Distribution of neuropeptides in rat pterygopalatine ganglion: light and electron microscopic immunohistochemical studies. AB - The distribution and quantity of neuropeptides in the rat pterygopalatine ganglion were studied by using complete serial paraffin sections of the ganglion immunostained with antiserum against several neuropeptides. The pterygopalatine ganglion, composed of 4932 +/- 291 (mean +/- SD) neurons, was triangular in shape with a tapering caudal tail. The most commonly found peptide in neurons was vasoactive intestinal polypeptide (VIP) (99.0%), followed by neuropeptide Y (NPY) (54.1%) and enkephalin (10.5%). The rostro-ventromedial and caudal parts of the ganglion where intensely VIP-immunoreactive neurons predominate project to the nasal mucosa, while the rostro-dorsolateral part of the ganglion where NPY immunoreactive neurons predominate projects to the Harderian gland. The coexistence of VIP/NPY (47.4%), VIP/NPY/enkephalin (6.6%) or VIP/enkephalin (3.9%) in the ganglionic neurons was recognized. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicosities formed synaptic contacts with the somatic spine or soma, which confirmed that the reflex arch, composed of axon collaterals of trigeminal ganglionic neurons and parasympathetic ganglionic neurons, operates through direct synapses. Enkephalin-immunoreactive varicosities, which were probably derived from parasympathetic preganglionic neurons, also made synaptic contact with the somatic spine. PMID- 1284206 TI - [Spontaneous motor activity in mice overloaded with iron-dextran]. AB - We studied the spontaneous motor activity and the levels of iron in brain (frontal cortex and striatum) and liver of mice overloaded with iron dextran. Two groups of mice injected intraperitoneally with two different doses of iron and the control group were used. We found a significant increase in the spontaneous motor activity only for the experimental group treated with the highest dose of iron. In frontal cortex and striatum the concentration of iron did not augment in the experimental groups. However, in liver we detected a highly significant rise in the iron content of both experimental groups. Our results suggest that the increase in the spontaneous motor activity observed in mice injected with the highest dose is not directly caused by changes in the iron concentration in the brain. PMID- 1284207 TI - Determining the neuronal connectivity of Golgi-impregnated neurons: ultrastructural assessment of functional aspects. AB - The combined light and electron microscopic analysis of Golgi-impregnated neural tissue is a potent tool for determining the connectivity of neural networks within the brain. In the experimental paradigms commonly applied in these studies, the Golgi-impregnated neurons are typically examined as the postsynaptic neuronal components. The structural characteristics and the pattern of distribution of their synaptic connections with other groups of identified neurons are analyzed. Due to the high power of resolution of the Golgi-electron microscopic technique, the ultrastructural analysis of Golgi-impregnated neurons can be expanded to elucidate activity-dependent structural alterations in their cytoarchitecture. These structural alterations can then be correlated under different physiological conditions with changes in the functional efficacy of the subcellular neuronal components. PMID- 1284208 TI - Quantitative aspects of synapses on Golgi-impregnated neurons. AB - With the classical Golgi techniques, numerous types of neurons can be distinguished in the cerebral cortex, each with a specific dendritic geometry and pattern of axonal ramifications. In the present review we describe two techniques which allow quantification of synapses on identified neurons: (1) Golgi-rapid impregnation-gold toning-electron microscopy, and (2) Golgi-Kopsch impregnation gold toning-electron microscopy in combination with staining of the tissue with ethanolic phosphotungstic acid (E-PTA). Both techniques were applied on neurons in the visual cortex of young and adult rabbits. By means of rotating and tilting specimens in the electron microscope, the nondistinctive ultrastructure of obliquely sectioned synapses can be circumvented, leading to precise estimates of asymmetrical vs. symmetrical synapses without complete reconstruction of the neuron. PMID- 1284209 TI - [Cryopreservation of erythrocytes with hydroxyethyl starch--already a procedure in routine clinical practice?]. PMID- 1284210 TI - [Cryopreservation of human erythrocytes with hydroxyethyl starch (HES)--Part 1: The procedure]. AB - Although the efficacy of hydroxyethyl starch (HES) as a cryoprotectant for human red blood cells (HRBC) was demonstrated in 1967, no clinical application has evolved so far. In contrast to glycerol, which has been widely used for this purpose, HES offers the advantage of being nontoxic if administered intravenously. Being also a plasma substitute, HES in combination with HRBC can normalize blood volume as well as oxygen transport in the case of extended blood loss. This may be of importance for autologous blood supply for elective surgery and for disaster treatment plans. For a volume of 40 ml, the optimal combination of important parameters [e.g. cooling rate 200-250 K/min, warming rate 400 K/min, hematocrit 40%, HES concentration 12% (w/w)] has led to a survival after thawing in terms of saline stability of 93 +/- 1% (n = 10). Additionally, the age prior to cryopreservation (0-3 days) had an influence on postthaw survival, but at least 90% survival can be obtained if the samples are washed 3-5 times before freezing. PMID- 1284211 TI - [Cryopreservation of human erythrocytes with hydroxyethyl starch (HES)--Part 2: Analysis of survival]. AB - Red blood cells (RBC) were obtained from 5 whole blood units by centrifugation and were purified using a simple washing procedure. Hematocrit and HES concentration in the 108-ml samples to be frozen were adjusted to 40% (v/v) and 12% (w/w), respectively. Cooling was performed by submerging into liquid nitrogen using containers to generate a flat sample geometry (3 mm thickness). After thawing in a shaking water bath, HES and free hemoglobin were removed in a simple washing step. To investigate the influence of the resuspension medium, the RBC were transferred into freshly drawn autologous plasma and into Locke's solution. Survival after thawing in terms of saline stability reached 86.3 +/- 2.3%. The cryopreservation procedure caused no major changes with regard to osmotic fragility, 2,3-DPG or intracellular Na+ and K+. ATP was reduced by 16%, but this had completely recovered after 3 h resuspension in autologous plasma. Some morphological changes present after thawing (e.g. stomatocytes, echinocytes) also recovered after 1.5 h. In conclusion, those RBC which survived the preservation process can be considered to be fully viable with regard to the parameters investigated. PMID- 1284212 TI - [The characteristics of the HIV isolated from HIV-infected persons and AIDS patients on the territory of the CIS]. AB - HIV strains were isolated from HIV-infected patients and AIDS patients in CIS. A total of 81 HIV isolates were obtained. The isolates were identified by using immunofluorescence and enzyme immunoassay, by determining the activity of reverse transcriptase, immunoblot, electron microscopy, polymerase chain reaction. Of the 81 isolates 79 were HIV-1 and 2 HIV-2. The strains differed in their infectivity, the kinetics of virus antigen accumulation, and the spectrum of susceptible cell lines. The viruses isolated may be assigned as two groups: high and low infective. The biological properties of the national HIV isolates were shown to be similar to the prototype HIV strains isolated elsewhere. PMID- 1284213 TI - [The possibilities of using immunological indices as criteria for determining the stage of HIV infection and the disease prognosis]. AB - The authors studied the immune status of 14 HIV-infected patients, 6 of whom had lymphadenopathy, 4 were diagnosed as having AIDS-related complex and 4, a full blown AIDS. Analysis of laboratory findings showed that of predictive value are serum levels of immunoglobulin B, a CD4 cell count less than 200, reduced populations of CD20 and CD16 lymphocytes, and a depressed response to pokeweed mitogen. Based on the clinical manifestations and laboratory results, three stages characterizing the immune system in HIV infection have been identified. PMID- 1284214 TI - [The expert diagnosis of HIV infection by radioimmunoprecipitation]. AB - Using a panel of sera from HIV-infected persons and donors, the authors showed that radioimmunoprecipitation assays compare favourably with immunoblotting assays. With radioimmunoprecipitation, cross reactions were observed between HIV 2 antigens and HIV-2 antibodies, and that the nature of cross reactivity differs from that observed with immunoblotting. Potentials of radioimmunoprecipitation assays as a confirmatory test for use with sera that have given indeterminate results in immunoblotting assays and contradictory results in enzyme immunoassays are examined. PMID- 1284215 TI - [The factors that affect the results of the serological diagnosis of HIV infection and the screening for anti-HIV]. AB - The laboratory diagnosis of HIV infection and screening for anti-HIV have determined the factors that influence the results of studies performed by ELISA and Western immunoblot. The factors include sensitivity and specificity of the test systems used, storage conditions of and transportation conditions for serum, errors of procedures for reactions, etc. Correlation is between the inactivation of the sera studied and the initial antibody titers during their storage at elevated temperatures. To obtain more valid results of HIV infection serodiagnosis it is necessary to use some test systems differing in the principles of setting up a reaction. PMID- 1284217 TI - [The choice of primers for polymerase amplification in the diagnosis of HIV infection]. PMID- 1284216 TI - [The methodological aspects in enhancing the efficacy of the epidemiological surveillance of HIV infection]. AB - Using a systems approach, the authors examined the main principles underlying an expert-based system for epidemiological surveillance over HIV infection. The principle objective is to control the processes which precede the occurrence of new infected cases and further spread of HIV infection. Accordingly, the system should address the following: epidemiological diagnosis and prediction of HIV incidence and spread, development of optimal preventive anti-epidemiological measures, research into how the infection spread. This should incorporate a database which is made by the hierarchic principle: the parameters of higher levels include those of lower level. So that the highest level would include two main integral estimates characterizing the risk of HIV from the outside (the first estimate) and the risk of HIV infection (the second estimate). PMID- 1284218 TI - [Biotechnical systems--new potentials for research in hygiene]. AB - The authors have worded the main assumptions of the present-day trends in hygienic studies based on the feedback biotechnical systems. It is suggested that biocontrol may be exercised on the basis of automated diagnosis of the hygienically significant conditions of the body. Concrete examples of deciding the indicated problems are reviewed. The principal advantage of the approach suggested lies in the perfection of the methodology of hygienic regulations on the basis of a direct effect of self-regulation of the body on the estimation of the concrete body-medium system. PMID- 1284219 TI - [Reverse transcriptase inhibitors and the therapy of HIV infection]. AB - Azidothymidine (retrovir) and didesoxyinosine, which represent nucleoside agents, are major remedies in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). The paper describes the molecular mechanism of their action. It implicates that triphosphates of these nucleosides selectively suppress the activity of reverse transcriptase (RNA-dependent DNA polymerase) of HIV by a termination mechanism. This results in effective inhibition of HIV reproduction and recovery of lymphocyte count and yields marked therapeutical benefits. The new generation anti-HIV agents are nucleoside-based phosphonates which were discovered by Russian investigators in 1987. The agents having a significant anti-HIV activity are low toxic. Emphasis is made on combined therapy of HIV infection, which holds much promise. PMID- 1284220 TI - [Methodological aspects in the theory of the setting of hygienic standards for pesticides in food products]. PMID- 1284221 TI - [The evaluation of the mutagenic hazard of atmospheric air pollution for an urban population]. AB - The authors describe the results of a genetic monitoring made in three towns of the Ukraine, which differ in the levels of polluted atmospheric air. Spontaneous abortions (SA) were selected as an index for genetic health of the population. The total number of CA, which were detected by primary documentation in the studied towns, the number of SA in early periods of pregnancy, and the incidence of SA, probably, of mutagenic origin, which is determined by multi-variance analysis, are greater in the contaminated towns than in comparatively pure towns. The findings suggest that the achieved level of atmospheric air pollution in some towns of the Ukraine is genetically significant. PMID- 1284222 TI - [Disordered integration of the immune and nervous systems in exposure to adverse environmental factors]. AB - Exposure to adverse environmental factors can result in the impaired relationships between the immune and nervous systems and hence increase autonomic properties of immunocompetent cells. This impairment may underlie some diseases associated with abnormal immunity. To have knowledge on the ways of restoring the integrative connections between the above systems will help maintain human health, augment its potential as a creator of the noosphere. PMID- 1284223 TI - [Disorders of the heart rhythm]. PMID- 1284224 TI - [The participation of prostanoids in the realization of the cardioprotective, antistressor and anti-arrhythmic effects of enkephalins]. AB - It has been established that preliminary administration of D-Ala2-Leu5-Arg6 enkephalin, D-Met2-Pro5-enkephalinamide, and D-phenylalanine to experimental animals prevents a stress-induced increase of the content of thromboxane in the blood plasma and myocardium and induces a rise of the level of prostacyclin, PGF2 and PGE in the heart and blood plasma. The authors hold that the changes in the level of prostanoids may mediate cardioprotective and anti-stressor rather than antiarrhythmic effects of enkephalins. PMID- 1284225 TI - [The neurohumoral mechanisms of adaptation to cryoinjury (frostbite)]. PMID- 1284226 TI - [Pancreatic juice peptides as possible regulators of reparative processes in the pancreas in acute and chronic pancreatitis]. AB - The experiments were performed on 34 dogs. The subcutaneous injection of boiled pancreatic juice was established to increase the survival of dogs in acute destructive pancreatitis (p < 0.001) and to decrease the specific volume damage to acinar (p < 0.01) and interstitial (p < 0.05) pancreatic tissue. It was also shown that boiled pancreatic autojuice exerted the therapeutic effect in chronic pancreatitis complicated by pancreatic fistulas. Five peptide components with a molecular mass from 4168 D to 1000 were discovered in the canine boiled pancreatic juice by liquid high pressure chromatography. Fractions with a molecular mass between 2187 and 1348 D were found to correspond to biologically active peptides, in particular to somatostatin. It is assumed that the therapeutic effect of boiled pancreatic juice used in acute pancreatitis may be due to somatostatin. Apparently pancreatic juice may turn an efficient therapeutic agent in acute pancreatitis and pancreatic fistulas. PMID- 1284227 TI - [The ajoene blockade of integrin-dependent processes in an HIV-infected cell system]. AB - Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide, isolated from extracts of garlic (Allium sativum) has been previously shown to inhibit platelet aggregation by inactivating allosterically the platelet integrin, GP IIb/IIIa. The structural and functional similarity of integrins led the authors to suggest that ajoene may also inhibit adhesive interactions and fusion of leukocytes. Synthetic stereoisomers of ajoene synthesized by the authors exhibited equal antiaggregatory activities (IC100 approximately 50 microM for platelets; IC100 approximately 10 microM for fMLP-stimulated neutrophils). Racemic ajoene inhibited the fusion of H9 cells with HIV-infected H9:RF cells (IC50 approximately 45 microM; 16 h of incubation) and also exhibited a degree of antiviral activity (IC50 approximately 5 microM as assessed by inhibition of HIV 1/CEM/Lav 1 Bru replication in CEM13 cells; m. o. i. 0.1; 72 h). A considerable increase in the latter became evident when the compound was administered in aliquots of 50 microM per 12 h of incubation (inhibition by 30%; total concentration 0.25 microM; 72 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284228 TI - [The trends in the management reorganization of medical science under market economy conditions]. PMID- 1284229 TI - Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia. AB - This article attempts correlating changes in cellular energy metabolism, acid base alterations, and ion homeostasis in ischemia and other conditions. It is emphasized that loss of ion homeostasis, with thermodynamically downhill fluxes of K+, Ca2+, Na+, Cl-, and H+, occurs because energy production fails and (or) ion conductances are increased. In ischemia, energy failure is the leading event but, in hypoglycemia, activation of ion conductances is what precipitates energy failure. The initial event is a rise in K+ e, at least in part caused by activation of K+ conductances modulated by Ca2+ or ATP/ADP ratio. Secondarily, this leads to release of excitatory amino acids and massive activation of unspecific cation (and anion) conductances. Production of H+ occurs in states characterized by energy failure (ischemia and hypoxia) or by alkalosis (hypocapnia and ammonia accumulation). H+ equilibrates between intra- and extra cellular fluid via nonionic diffusion of lactic acid, and transmembrane fluxes of H+ or HCO3- via ion channels. Since the relationship between lactate and either pHi or pHe is linear, there are no abrupt pH shifts explaining why hyperglycemia worsens ischemic damage. The reversible insults seem to induce a sustained stimulation of H+ extrusion from cells giving rise to intracellular alkalosis and extracellular acidosis. PMID- 1284230 TI - Astrocytes, as well as neurons, express a diversity of ion channels. AB - The electrophysiologist's view of brain astrocytes has changed markedly in recent years. In the past astrocytes were viewed as passive, K+ selective cells, but it is now evident that they are capable of expressing voltage- and ligand-activated channels previously thought to be restricted to neurons. The functional importance of most of these ion channels is not understood at present. However, from studies of astrocytes cultured from different species and brain regions, we learned that like their neuronal counterparts astrocytes are a heterogeneous group of brain cells showing similar heterogeneity in their ion-channel expression. Not only are subpopulations of astrocytes within areas of the brain equipped with specific sets of ion channels but, furthermore, regional heterogeneity is apparent. In addition, astrocyte ion channel expression is dynamic and changes during development. Some ion channels are only expressed postnatally, yet others appear to be expressed only during certain stages of development. Interestingly, the expression of some astrocyte channels, including Na+, Ca2+, and some K+ channels, appears to be controlled by neurons via mechanisms that are presently unknown. Some studies suggest roles for astrocyte channels in basic cell processes such as cell proliferation. Thus, although the role of some astrocyte channels remains unclear, our understanding of astrocyte physiology is starting to take shape and points towards roles of ion channels not involved in electrogenesis. PMID- 1284232 TI - Molecular mechanisms of open-channel blockade in nicotinic acetylcholine receptors of autonomic ganglia neurons. AB - The results of recent attempts to estimate the dimensions of ionic channels in nicotinic acetylcholine receptors of sympathetic and enteric ganglia neurons are reviewed. The channel dimensions, obtained from comparison of the sizes of the open-channel blocking molecules with their blocking activities, are 6.1 x 8.3 A (1 A = 0.1 nm) in both sympathetic and enteric ganglia. None of the competitive ganglionic blockers fit within this channel size. In addition, a chemical structure that binds the open-channel blockers in ganglionic nicotinic acetylcholine receptors is suggested to be formed by serine and threonine residues, as found by comparing the differences between the structures of the neuronal and muscle nicotinic acetylcholine receptors with the differences in their pharmacology. PMID- 1284231 TI - Aminergic and peptidergic elements and actions in a cardiac parasympathetic ganglion. AB - Correlated histochemical, immunocytochemical, and electrophysiological experiments have been undertaken to identify putative neurotransmitter neuromodulator substances in cells and fibers in the parasympathetic cardiac ganglion of the mudpuppy, Necturus maculosus, and to determine the action of these agents on the properties of the parasympathetic postganglionic neurons. The mudpuppy cardiac ganglion contains two neuron types: large parasympathetic postganglionic neurons and smaller intrinsic neurons initially identified as small intensely fluorescent cells. We have shown that the postganglionic neurons contain both acetylcholine and a galanin-like neuropeptide. Also, we have demonstrated that the intrinsic neurons contain a number of different biogenic amines such as dopamine and serotonin, as well as neuropeptides including a substance P-like peptide and a galanin-like peptide. The results of these studies indicate that the anatomical and histochemical organization of the mudpuppy cardiac ganglion is more complex than that seen in other amphibians and is very similar to that found in most mammalian species. Previously, we showed that galanin has actions that make it of interest as a potential inhibitory neurotransmitter in the mudpuppy cardiac ganglion. Galanin hyperpolarizes and decreases membrane excitability in most parasympathetic neurons. Here we show that galanin initiates membrane hyperpolarization by activating a voltage- and time-dependent potassium conductance. We also present the initial results of ongoing studies which indicate that calcitonin gene-related peptide can depolarize some of the parasympathetic neurons as well as evidence that serotonin initiates depolarization in many parasympathetic neurons. This serotonin-induced depolarization consists of an initial transient depolarization followed by a longer, more slowly developing depolarization. Action potential activity is stimulated during the initial period of depolarization, but depressed during the later, slow depolarization. The results of these electrophysiological experiments suggest that many of the bioactive substances that have been identified in the different cells and nerve fibers within the cardiac ganglion affect the excitability of the postganglionic neurons. In conclusion, we suggest that the results of the studies summarized in this review demonstrate that the cardiac ganglion in the mudpuppy is not simply a relay station. Rather, the cardiac ganglion has a complex organization and exhibits a diversity of physiological responses, indicating that it very likely is another site of integration for control of cardiac function. PMID- 1284234 TI - Myelin associated glycoproteins confer heterophilic adhesion properties to an immortalized optic nerve derived cell line. AB - We have transfected an immortalized optic nerve-derived cell line with the cDNA's encoding the two isoforms of MAG. Our aim was to assess whether expression of L MAG (72 KDa) and S-MAG (67 KDa) in these cells confer adhesion properties when a suspension of single cells is allowed to aggregate. The selected cell lines expressed MAG mRNAs and proteins of the appropriate molecular size, and the proteins were targeted correctly to the plasma membrane. Both L-MAG and S-MAG expressing transfectants exhibited enhanced self-adhesive properties, aggregating with faster kinetics and forming larger aggregates than MAG-negative control cells. The interaction appears to be mostly heterophilic since MAG+ and MAG- cells which were labeled with a fluorescent probe bound equally well to pre aggregated MAG+ transfectants and their interaction was blocked by monoclonal anti-MAG antibodies. A further finding which supports the role of MAG in adhesion was the observation that MAG was preferentially localized at the junctions between cells, in confluent cultures. PMID- 1284233 TI - Inhibition of neutrophil priming and tyrosyl phosphorylation by cepharanthine, a nonsteroidal antiinflammatory drug. AB - Receptor-mediated superoxide (O2.-)-generation and tyrosyl phosphorylation of neutrophil proteins, such as 58, 65, 84, 108 and 115 kDa, were enhanced by priming cells with granulocyte colony stimulating factor (G-CSF) [Akimura, K. et al. Arch. Biochem. Biophys. 298: 703-709, 1992]. To elucidate the possible involvement of tyrosyl phosphorylation of neutrophil proteins in the enhancing mechanism of O2.- generation, the effect of cepharanthine, a biscoclaurine alkaloid that inhibits phorbol 12-myristate 13-acetate (PMA)- and receptor mediated O2.- generation, on the priming of human peripheral neutrophils (HPPMN) was studied. Both enhancement of formyl-methionyl-leucyl- phenylalanine (FMLP) mediated O2.- generation and tyrosyl phosphorylation of some neutrophil proteins, i.e., 115, 108 and 84 kDa proteins, by HHPMN after treatment with G-CSF were strongly inhibited by cepharanthine in a concentration- and treatment-time dependent manner. In contrast, inhibition of PMA-mediated O2.- generation by cepharanthine was weak and independent of treatment time. These results suggest that cepharanthine might inhibit the priming step of neutrophil activation concomitantly with its inhibition of the tyrosyl phosphorylation of some neutrophil proteins that might underlie the mechanism for priming of neutrophils with G-CSF. PMID- 1284235 TI - Diagnostic value of analysis of cystatin C and protein HC in biological fluids. AB - Cystatin C, a 13 kDa-protein, is produced by most nucleated cells and is catabolized by the renal tubular cells after passing the glomerular filter. It belongs to the family 2 of the cystatin superfamily of proteins. The function of cystatin C is to regulate the activity of cysteine proteinases and cystatin C seems to be the main cysteine proteinase inhibitor of most investigated human biological fluids. Its normal level in plasma is 0.8-2.5 mg/l, in cerebrospinal fluid 4-14 mg/l and in urine 0.03-0.3 mg/l. The production rate of cystatin C is remarkably constant and its plasma concentration can therefore be used as a reliable measure of the glomerular filtration rate (GFR). Indeed, the cystatin C plasma concentration is more closely correlated to the GFR than the plasma levels of creatinine and all other investigated low molecular weight proteins, including beta 2-microglobulin and retinol binding protein. Protein HC, alias alpha 1 microglobulin, is produced by the liver as a 27 kDa-glycoprotein. It belongs to the lipocalin superfamily of hydrophobic ligand binding proteins and more than 50% of the normal plasma amount of protein HC is present as a high molecular weight HC-IgA complex carrying antibody activity. The plasma concentration of free protein HC is, in contrast to that of HC-IgA, mainly determined by the GFR. The normal values for the plasma concentrations of HC-IgA and free protein HC are 36-620 mg/l and 14-26 mg/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284236 TI - Utility of filtration markers to monitor the quality of glomerular function. AB - Diabetes mellitus can lead, along the years of its course, to chronic renal failure in a high proportion of cases. An early risk-indicator of later diabetic nephropathy is the presence of microalbuminuria, but it usually takes about fifteen to twenty years to appear. Before that, no clinical signs can disclose the underlying alterations of glomerular basement membrane that will eventually bring forth overt nephropathy. The usefulness of the altered excretion of isoenzymes of amylase as an early marker of the glomerular charge selectivity was tested in 202 juvenile onset insulin-dependent diabetics, compared with 51 normal subjects matched for age and sex. The diabetic patients studied showed increased excretion of salivary amylase into urine. The salivary to pancreatic amylase ratio of concentrations in urine was always below 1 in normal subjects, and was increased over 1 in 33.2% of diabetics, although microalbuminuria was present only in 26.2% of patients. The excretion of other proteins was within reference values in the majority of cases, indicating that the kidney was not seriously affected in those patients. Moreover, the altered salivary to pancreatic amylase ratio in urine was more prevalent than microalbuminuria (36.6% vs 18%) in the first decade of the evolution of the diabetes. These results indicate that the ratio of excretions of both isoamylases into urine is a more sensible and earlier marker of altered glomerular charge barrier for anionic proteins. PMID- 1284237 TI - Spatially restricted expression of fibroblast growth factor receptor-2 during Xenopus development. AB - The fibroblast growth factors (FGFs) play a role in Xenopus laevis embryonic development, particularly in the induction of ventral-type mesoderm. We have isolated a full-length cDNA from Xenopus that we have designated Xenopus fibroblast growth factor receptor-2 (XFGFR-2), with significant amino acid sequence similarity to the previously described bek gene (FGFR-2). We expressed the XFGFR-2 cDNA in COS1 cells and showed that it functions as an FGF receptor by binding radiolabeled FGF-2. RNA gel blot analysis demonstrates that unlike Xenopus fibroblast growth factor receptor-1 (XFGFR-1), XFGFR-2 mRNA expression begins during gastrulation and continues through early tadpole stages. Whole mount in situ hybridization demonstrates that XFGFR-2 mRNA is localized to the anterior neural plate in early neurula stage embryos. Later in development, XFGFR 2 expression is found in the eye anlagen, midbrain-hindbrain boundary and the otic vesicle. In addition, XFGFR-2 transcripts are expressed in animal caps in a manner that is independent of mesoderm-inducing factors. These results indicate that XFGFR-2 may have a role in development that is distinct from that of XFGFR 1. PMID- 1284238 TI - Timing of neuronal death following successive blockade of protein synthesis and axoplasmic transport in the axonal target territory. AB - Neurons in the isthmo-optic nucleus (ION) of chick embryos can withstand a substantial cycloheximide-induced reduction in protein synthesis in their target territory, the retina, at the very time when their survival is known to depend on a retrograde signal from the latter. We here test the hypothesis that this resistance to the cycloheximide injection might be due to the accumulation in the ION of a reserve of retina-derived trophic molecules (or of resulting second messengers). Following an intraocular injection of cycloheximide at E15 to deplete the hypothetical reserve in one ION, both eyes received injections of colchicine (which blocks axoplasmic transport) at E16. The resulting time course of cell death was very similar in the two IONs, which refutes the hypothesis. The most plausible alternative is that there is a reserve of trophic substance in the retina capable of maintaining the ION for about 1 day. PMID- 1284239 TI - Endogenous and exogenous alpha-fetoproteins as differential markers of cultured neonatal mouse Schwann cells and fibroblasts. AB - alpha-Fetoprotein (AFP) and AFP-gene transcripts were demonstrated in vitro in Schwann (S) cell and fibroblast (F) cell cultures of neonatal mouse origin. All S and F cells of primary cultures and of established cell lines expressed the AFP gene. AFP mRNA was detected by an in situ hybridization technique using a 35S-AFP cDNA probe. AFP was localized by immunocytoperoxidase labelling using purified anti-AFP antibodies. The amounts of stained endogenous AFP, estimated semiquantitatively, were about 3-fold higher in S cells than in F cells. After incubating the cultures with exogenous mouse AFP, both S and F cells showed significant ability to take up the protein; the amount of internalized protein was found to be higher in F cells than in S cells. Moreover, the uptake of AFP fluorescein conjugates (FITC-AFP), estimated quantitatively by fluorometry, also gave higher values for F cells. The cytoplasm of F cells exhibited a characteristic fluorescence pattern, strongly illuminated and dispersed grains; the cytoplasm of S cells was regularly labelled. If exogenous FITC-AFP uptake could be used to distinguish labelled F cells from S cells (with application for identification and selection of F cells), the immunocytochemically stained endogenous AFP could allow S cells to be distinguished from F cells (using the dilutions of antibodies still staining the S cells but which lead to the absence of F-cell labelling). The two procedures, which can be used independently or together, may constitute differential markers for S cell and F cultures in, i.e., nerve regeneration of neurofibroma studies using the model of mixed S and F culture also containing other types of cells. PMID- 1284240 TI - Ultrastructural localization of basic lysine-rich proteins during the nucleologenesis in preimplantation bovine embryos. AB - The process of nucleologenesis was examined in preimplantation bovine embryos by using ethanolic phosphotungstic acid (E-PTA) at the electron microscopic level. E PTA binds basic lysine-rich proteins and thus makes possible detection of their localization and distribution. In blastomere nuclei of 2-, 4- and early 8-cell embryos, only nucleolus precursor body/bodies (NPBs) appear, being formed from a mass which is homogeneously stained with E-PTA. In cow embryos, the whole nucleologenesis is situated in the 8-cell stage. During the following step of nucleologenesis, the NPB with a big central area (named NPB vacuole) is formed. Fibrillar mass around the central vacuole is intensively stained, especially in the regions in close vicinity to the central vacuole. Many clumps of E-PTA positive, regularly dispersed material are found inside the vacuole. The next step of nucleologenesis is characterized by the presence of NPB with secondary vacuoles that are also filled with clumps of E-PTA-positive material. Small, intensively stained areas are visible at sites that are probably identical with those where a dense fibrillar component is formed. Until the end of the 8-cell stage, as well as in the morula and early blastocyst, typical fibrillogranular nucleoli are present. These nucleoli have 3 basic components--fibrillar centres (FC), dense fibrillar components (DFC) and granular components (GC) which stain with different increasing intensity. FC and DFC show a strong (particular) reaction while the GC are stained to a lesser degree. In all examined stages of embryonal development, the E-PTA positivity was found within the perinucleolar chromatin and on the clumps of heterochromatin. An analogical localization of basic and acidic regulatory proteins in the examined developmental stages is discussed. PMID- 1284241 TI - A novel panel of monoclonal antibodies against beta-galactosidase of Escherichia coli and its versatility for detection of recombinant expression products. AB - A panel of seven mouse monoclonal antibodies (BG-O1 - BG-07) raised against beta galactosidase (beta-gal) from E. coli was characterized in respect of their binding to beta-gal and to fusion proteins. The antibodies were beta-gal specific, recognized six different antigenic determinants on beta-gal molecule and some of them inhibited catalytical activity of the enzyme. The antibodies reacted with C-terminal beta-gal fusion proteins in the native state as well as after Western blotting. BG-02 antibody was successfully used for immunofluorescence detection of cells transfected with vectors containing the lacZ gene. PMID- 1284242 TI - [Changes in the serological indices of the immune status of workers in contact with raw foodstuffs contaminated by mycotoxins]. AB - The immune status was estimated in workers engaged into the grain processing and exposed to constant hazards of the industrial environment (contact with the goods contaminated by mycotoxins). Studies revealed in workers the certain changes of serum Ig, complement fractions, proteins of the acute phase of inflammation. The importance of immunologic changes as criteria for adequate prophylactic measures was stressed. PMID- 1284243 TI - Growth in malnutrition related to gastrointestinal diseases: coeliac disease. AB - Coeliac disease in children is frequently associated with a slow growth rate. This observation may be linked to the malabsorption that occurs in these patients; however, the underlying mechanism remains unknown. To better understand this phenomenon, we have studied the growth patterns of 153 patients with coeliac disease for 2-9 years. Gastro-intestinal biopsies were performed before and after gluten exclusion. In a second group of 79 children, somatostatin levels and binding properties in the plasma and jejunal mucosa were measured. In a third group of 40 patients we measured insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGF-BP3) levels. We found that in children diagnosed before 2 years of age weight was the most affected growth parameter. In children diagnosed after this age, height was more affected. Suppression of gluten intake induced an acceleration of growth velocity. Although plasma levels of somatostatin were not significantly altered, somatostatin concentrations in the jejunal mucosa of patients in the active phase of the disease were significantly elevated (p < 0.05). Children with coeliac disease exhibited significantly lower levels of IGF BP3 when compared to patients with normal stature and growth velocities. In contrast, these patients showed an increase in IGF-BP3 levels after gluten exclusion from the diet. PMID- 1284244 TI - Immunofluorescence detection of the vimentin epitope in chromatin structures of cell nuclei and chromosomes. AB - We describe immunofluorescence detection of the vimentin epitope, recognized by monoclonal antibody VI-01, in chromatin structures of eukaryotic cell nuclei and chromosomes. The approach used is based on increased sensitivity of 5 bromodeoxyuridine (BrdU)-substituted DNA to UV irradiation-induced crosslinking of DNA with proteins in vivo, by which the proteins interacting with chromosomal DNA can be immunovisualized in situ. PMID- 1284246 TI - The primary structure of porcine aminoacylase 1 deduced from cDNA sequence. AB - A cDNA encoding the complete amino acid sequence of aminoacylase 1 (N-acylamino acid aminohydrolase, ACY-1) [EC 3.5.1.14], a dimeric metalloprotein having two Zn2+ in the molecule, which catalyzes the deacylation of N-acylated L-amino acids except L-aspartic acid, has been isolated from porcine kidney lambda gt10 cDNA library and sequenced. From sequence analysis of the cDNA and the N- and C terminal amino acid analyses of the purified protein, it is deduced that porcine kidney ACY-1 consists of two identical subunits (M(r) 45,260), each of which consists of a single chain of 406 amino acids with acetylalanine at the N terminus. A cDNA encoding porcine liver ACY-1 was also cloned. The amino acid sequence deduced from the nucleotide sequence of the cDNA from porcine liver was identical to that deduced for porcine kidney ACY-1. Northern blot analysis suggested that ACY-1 is more highly expressed in kidney than in liver. Comparison of the amino acid sequence of porcine ACY-1 with those of other Zn2+-binding metalloenzymes showed no significant homologies in either the overall sequence or the consensus sequences for the metal binding sites. This indicates that ACY-1 is a new type of metalloprotein. PMID- 1284247 TI - Isolation of cDNA for bovine stomach 155 kDa protein exhibiting myosin light chain kinase activity. AB - Two proteins with myosin light chain kinase activity and electrophoretic molecular weights of 155,000 and 130,000 were each isolated from bovine stomach smooth muscle [Kuwayama, H., Suzuki, M., Koga, R., & Ebashi, S. (1988) J. Biochem. 104, 862-866]. The 155 kDa component showed a much higher superprecipitation-inducing activity than the 130 kDa component, when compared on the basis of equivalent myosin light chain kinase activity. In this study, we isolated a cDNA for the entire coding region of the 155 kDa protein. The deduced amino acid sequence revealed a high degree of similarity to those of chicken and rabbit smooth muscle myosin light chain kinases. Multiple motifs, such as three repeats of an immunoglobulin C2-like domain, a fibronectin type III domain, and unusual 20 repeats of 12 amino acids were detected in the sequence. Part of the amino-terminal sequence was similar to that of the actin- and calmodulin-binding domain of smooth muscle caldesmon. These observations suggest that the 155 kDa protein has additional functions other than its enzymatic activity. Two mRNAs of 6.0 and 2.6 kb in length in the bovine stomach smooth muscle RNAs were hybridized with cDNA probes. The 2.6-kb RNA probably encodes telokin, which is the carboxyl terminus of smooth muscle myosin light chain kinase. mRNAs with identical lengths were also detected in bovine aorta. PMID- 1284245 TI - Differential expression of insulin-like growth factors I and II (IGF I and II), mRNA, peptide and binding protein 1 during mouse palate development: comparison with TGF beta peptide distribution. AB - Development of the mammalian secondary palate involves a series of epithelial mesenchymal interactions: during one of these, a mesenchymal signal specifies regionally distinct palatal epithelial differentiation. Extracellular matrix molecules and soluble growth factors may be involved in this signalling process. In this study, we have mapped the expression of the genes for insulin-like growth factors (IGF I and II), the peptides they encode, and the IGF binding protein 1 (IGF BP-1) during murine palatogenesis (embryonic days (E) 12-15). IGF-I gene expression was below detectable levels in the craniofacial region at all ages. IGF-I peptide was at the threshold of immunocytochemical detection and widely distributed in the palatal mesenchyme, decreasing in staining intensity from E12 to E14. By contrast, IGF-II mRNA was intensely localised in several tissues. IGF II gene expression within the forming palate was developmentally regulated. In the vertical palatal shelves (E12 to E13) IGF-II gene expression was absent. On early E14, in the horizontal prefusion palate, significant expression was present in the palatal mesenchyme, but not the epithelium. Once palatal fusion had occurred, mesenchymal expression fell rapidly to undetectable levels. IGF-II mRNA was next detectable in the secondary palate on late E15 at sites of membranous bone formation. By contrast to the mRNA distribution, IGF-II peptide was localised predominantly in the palatal epithelia (particularly the nasal and medial edge epithelia) but also in the mesenchyme of the E14 prefusion palate. Significantly, the IGF binding protein had a similar distribution pattern to the IGF-II peptide. At all ages, the developing tongue myotubes labelled heavily for IGF-II mRNA, protein and binding protein. These data suggest that IGF-II may play a localised paracrine role during murine palatogenesis, perhaps in the mesenchymal signalling of epithelial differentiation. IGF-II may also serve to coordinate the development of the tongue and palate. The distribution of IGF-II peptide was very similar to that of TGF-beta, suggesting a possible interactive role of these growth factors during palate development. Finally, evidence that the IGF-II gene is imprinted (Ferguson-Smith et al. 1991) and may be the target for uniparental disomy in the human Beckwith Wiedemann syndrome (Henry et al. 1991), which is characterised by the overgrowth of tissues (especially the tongue) expressing IGF II in the embryo, indicates the necessity of reanalysing human cleft palate families for disruption (including uniparental disomy) of the genes encoding IGFs, their receptors and binding proteins. PMID- 1284248 TI - Molecular cloning and partial characterization of a novel collagen chain, alpha 1(XVI), consisting of repetitive collagenous domains and cysteine-containing non collagenous segments. AB - In an effort to identify new members of the collagen family, we screened a human placenta cDNA library with a collagenous probe. A novel 3.7 kb cDNA was identified encoding an open reading frame of 1,186 amino acids and containing a termination codon. The predicted polypeptide consists of 9 repetitive collagenous (stretches of Gly-X-Y) and several non-collagenous segments. Two cysteinyl residues separated by two amino acid residues (Cys-X-X-Cys) are regularly located in the N-terminal region of each non-collagenous segment. The deduced amino acid sequence described above is distinct from those of known types of collagen. Therefore, this novel collagen chain is designated alpha 1(XVI). Northern blot analysis revealed an alpha 1(XVI) mRNA of 5.2 kb, indicating that the overlapping cDNA clones isolated in this study covered nearly three-fourths of the mRNA. As a tool for further study on the expression of type XVI collagen, we prepared an antibody against the nonadecapeptide CFLSLERPRAEEARGDNSE, derived from the putative translation product of the cDNA. In immunoblot analysis, the antibody recognized a 160 kDa protein, which was bacterial collagenase-sensitive. Immunohistochemical stainings of human placental tissues with anti-peptide antibody revealed a positive reaction with amnion, the membranous tissue lining the amniotic cavity. The gene of alpha 1(XVI) chain, COL16A1, is mapped on the short arm of human chromosome 1 (1p13-p34). PMID- 1284249 TI - Importance of tyrosine phosphatases in the effects of cell-cell contact and microenvironments on EGF-stimulated tyrosine phosphorylation. AB - We have compared the EGF responses of A431 cells when grown as monolayers at a variety of cell densities or as multicellular spheroids in order to investigate the effects of cell contact and 3-dimensional structure on signal transduction. Proliferation of the A431 squamous carcinoma cell line grown in our laboratory was unaffected by EGF when grown in monolayer culture. As 3-dimensional, multicellular spheroids, however, growth was stimulated by EGF. The maximum volume attainable in the presence of EGF was more than 30 times that in its absence. EGF-dependent tyrosine phosphorylation was compared under these conditions by immunohistochemistry and Western blotting. In initial experiments using published procedures, tyrosine phosphorylation was density-dependent in monolayers and undetectable in spheroids. However, the density-dependence was abolished by the addition of high concentrations of protein tyrosine phosphatase inhibitors (1 mM Zn++ and VO4(3)-). The density dependence of EGF-stimulated tyrosine phosphorylation in monolayers was, therefore, largely the result of changes in phosphatase activity rather than kinase. Using high concentrations of phosphatase inhibitors, phosphotyrosine was clearly visible by immunohistochemistry in the outermost cells of spheroids, but it was still not visible in the spheroid center. The lack of response within the spheroid was not related to the presence of EGF receptor nor diffusion of EGF. In companion experiments, we showed that staining for EGF receptor was present homogeneously throughout the spheroid and that EGF penetrated to its center under the conditions of the experiment. Thus, although an increase in tyrosine phosphatase activity was a major factor affecting tyrosine phosphorylation in the outer cells, other factors were important in the inner cells. We concluded that an increase of tyrosine phosphatase activity was the most important component of the adaptation of the EGF signal transduction system to high cell density in monolayer cultures. In spheroids, tyrosine phosphatases are also enhanced, but other factors, such as autocrine synthesis of TGF-alpha and possibly the cellular distribution of EGF receptors and cell shape, play a role. PMID- 1284250 TI - Regulation of programmed death in erythroid progenitor cells by erythropoietin: effects of calcium and of protein and RNA syntheses. AB - Erythropoietin (EPO) retards DNA breakdown characteristic of programmed cell death (apoptosis) and promotes survival in erythroid progenitor cells. The mechanism by which EPO inhibits programmed death is unknown. In the well characterized model of glucocorticoid-treated thymocytes, activation of a Ca2+/Mg(2+)-sensitive endonuclease and new protein and RNA syntheses have been found necessary for apoptosis. We examined the effects of EPO on the free intracellular calcium ion concentration ([Ca2+]i), and the roles of Ca2+ and RNA and protein syntheses on DNA cleavage in erythroid progenitor cells. The murine model of erythroid differentiation using Friend leukemia virus-infected proerythroblasts (FVA cells) was used. EPO did not affect the [Ca2+]i in FVA cells. Decreasing [Ca2+]i by extracellular Ca2+ chelation with EGTA facilitated DNA breakdown. Increasing [Ca2+]i with the calcium ionophore 4-bromo-A23187 increased DNA cleavage; however, DNA fragments generated by high [Ca2+]i were much larger than those seen in the absence of EPO or presence of EGTA. Increased [Ca2+]i also inhibited DNA breakdown to small oligonucleosomal fragments characteristic of cells cultured without EPO. However, no concentration of ionophore protected the high molecular weight DNA as did EPO. Cycloheximide inhibited DNA breakdown in a dose dependent manner in cultures lacking EPO, but two other protein synthesis inhibitors, pactamycin and puromycin, did not prevent DNA breakdown. Inhibition of RNA synthesis with actinomycin D did not prevent DNA breakdown. Cells with morphological characteristics similar to those reported in other cells undergoing programmed death accumulated in EPO-derived cultures. These studies demonstrate that although DNA cleavage and morphological changes are common to apoptotic cells, the roles for Ca2+ and protein and RNA syntheses are not universal and suggest that apoptosis can be regulated by different biochemical mechanisms in different cell types. PMID- 1284251 TI - Influence of atrial fibrillation on coagulo-fibrinolytic markers in patients with cerebral infarction. AB - To examine the influence of atrial fibrillation (Af) on stroke onset, we measured the plasma D-dimer level, thrombin antithrombin III complex and plasmin alpha 2 antiplasmin complex (PAP) in 46 stroke patients with Af and 87 stroke patients without Af. These marker levels were significantly higher in Af patients with stroke than in those without stroke (n = 16), and thus do not seem to be affected by Af alone. Abnormal values were also more frequent in acute Af stroke patients with visible occlusion of the major cerebral artery than in those without Af. The D-dimer and PAP levels in all Af stroke patients in the younger-aged patients (< or = 64 years) were significantly higher than those without Af, but not noted in the older-aged group (> or = 75 years). These results suggest that the D-dimer and PAP levels in younger-aged patients with Af indicate the existence of cerebral emboli due to Af. PMID- 1284253 TI - Long-term prostacyclin--treatment acts on the DNA and RNA content of rat gastric (antral and fundic) mucosa dose-dependently. AB - The changes in gastric (antral and fundic) mucosal DNA and RNA contents were investigated in long-term (80 days) treatment of rats with orally administered prostacyclin. Prostacyclin caused a dose-dependent, significant increase of the DNA levels in both parts of the gastric mucosa together with a significant thickening of the fundic mucosa. The observed changes (decrease) of the RNA/DNA ratio in the fundic as well as antral mucosa, are interpreted as a sign of accelerated cell renewal, i.e. hyperplasia. PMID- 1284252 TI - [Biochemical indices of liver function in workers from repair brigades in chemical plants "Organika-Azot" in Jaworz]. AB - In order to assess the functional state of the liver in 45 repair service workers of a chemical plant producing pesticides the serum concentration and electrophoretic pattern of proteins, the concentration of bilirubin and the activity of alkaline phosphatase, gamma-glutamyl- transpeptidase, alanine and aspartate aminotransferase, and lactic and malic dehydrogenase were determined. As compared to 35 healthy controls, not exposed to noxious chemicals, a significantly lower serum protein concentration with higher percentage of gamma globulins and lower albumins and alpha 2-globulins were observed, the serum alanine and aspartate aminotransferase activities were significantly elevated. Ultrasound examination of the hepatic structure revealed liver steatosis in 11 (24.4%) workers. The results of our study point to a discrete lesion of the liver. PMID- 1284254 TI - CSF 5-HIAA as a predictor of treatment response in trichotillomania. AB - Trichotillomania is characterized by chronic hair-pulling resulting in noticeable hair loss. In a preliminary study, cerebrospinal fluid (CSF) measures in 8 medication-free, female, trichotillomania patients were compared to those of matched, normal controls. There was no difference between patients and controls in measures of CSF cortisol, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). CSF measures did not correlate with measures of trichotillomania symptomatology. However, degree of response to treatment with serotonin re-uptake inhibitors significantly correlated with baseline CSF 5-HIAA. This suggests that central serotonin turnover is specifically relevant to treatment response to serotonin re-uptake inhibitors in trichotillomania. PMID- 1284255 TI - Antiviral agents in the treatment of chronic viral hepatitis. PMID- 1284256 TI - [Anti-HCV antibodies against the structural and nonstructural antigens of hepatitis C in people seropositive in the second generation test]. AB - Forty six anti-HCV repeatable positive (the 2nd generation Abbott EIA test) adults, among which 26 were blood donors and 19 were patients with chronic hepatitis, were tested using Abbott HCV EIA Supplemental Assay. The test renders possible to conduct separate investigation antibodies against structural and nonstructural antigens of HCV. In 44/45 (97.8 per cent) cases was an agreement of the results with the 2nd generation test. In the most of cases (80 per cent) both types of antibodies were present. However, in 20 per cent of blood donors the antibodies against structural HCV antigen were not present whereas all the chronic hepatitis patients had these type of antibodies. PMID- 1284257 TI - [Ophthalmic zoster in clinical material from the clinic of infectious diseases PAM in Szczecin during 1985-1989]. AB - Clinical course, early and late complications as well as treatment of ophthalmic zoster in 70 hospitalized patients are presented. Authors pay the attention to early treatment (general and topical) with Zovirax in prevention of ocular complications. PMID- 1284258 TI - [Molecular mimicking. A very conservative nature and astute microbes]. PMID- 1284260 TI - [Concentration of prealbumin, ceruloplasmin, alpha-macroglobulin and haptoglobin in blood serum of patients with chronic non-A, non-B hepatitis treated with hemodialysis for chronic renal failure]. AB - In 25 patients with chronic renal failure, treated with haemodialysis (13 patients with chronic non-A, non-B hepatitis, and 12 cases without evidence of hepatocellular damage), and in 20 healthy persons, blood serum concentrations were determined of prealbumin, ceruloplasmin, alpha 2-macroglobulin, and haptoglobin. It was found that the concentrations of these proteins in both subgroups of patients were not significantly different. The concentration of prealbumin was higher, and that of alpha 2-macroglobulin and haptoglobin was significantly lower in comparison with healthy subjects. PMID- 1284259 TI - [The effect of starvation on mast cell functional activity and on the content of microsomal cytochromes in the liver]. AB - Histamine secretion and ATP levels were measured in mast cells from the abdominal and pleural cavities of Wistar rat males (250-300 g) which had been starving for 2-4 days. Food deprivation had no effect on histamine levels and secretion in exposure to substance 48/80. ATP concentration got reduced from starvation day 2. Food deprivation for 2 days led to decline in the content of cytochromes P-450, P 450B, in the ratio P-450B/P-450L, but had no effect on rat liver cytochrome B5. 4 day starvation did not entail further changes. PMID- 1284261 TI - [Diagnostic value of prostatic specific antigen (PSA) in comparison to prostatic acid phosphatase (PAP) in prostatic cancer and adenoma]. AB - The diagnostic value of the tumour markers: PSA, PAP and AcP was studied before treatment in 379 men (47 with prostatic cancer--PC, 306 with benign hyperplasia- PBH, and 26 healthy subjects--control group CG). PSA was determined by the enzymoimmune method, and the phosphatases were evaluated by the spectrophotometric method. Raised level of PSA was found in PBH--the highest value--23.3 ng/ml. After accepting the cutting off values (1.9 ng/ml and 23.3 ng/ml), even in 93% of patients with PC, the level of PSA exceeded the second of those values. A significant growing tendency was found of PSA together with the degree of clinical progression of PC (in stages C and D--in 100% of patients). PSA, as compared with the phosphatases, is a much more sensitive biochemical marker, exceeding them many times in sensitivity. PMID- 1284262 TI - [Quality of life as a catch phrase and promoter in the pharmaceutical industry]. AB - Quality of life (QL) is an expression of the degree to which a tumor patient is satisfied and copes with his life and the therapy which is being administered. QL is influenced by physical, psychological and social factors as well as by time. During the individual course of a malignant disease and its therapy, changes in QL need to be assessed with the appropriate "measuring instruments". Once the quality of the data has been assured, comparisons can be made with respect to the influence of alternative therapies on QL. This is where "promotional" information from the pharmaceutical industry can be emphasized; QL degenerates to a useless term, however, if it is used indiscriminately and without proper validation of the data. A new concept, i.e. QUALYs (= Quality Adjusted Life Years), has originated in the USA, which attempts to add a dimension of currency value to the term LQ. PMID- 1284263 TI - Evaluation of expanded polytetrafluoroethylene (e-PTFE) and autogenous fascia lata in frontalis suspension. A comparative clinical study. AB - Ptosis palpebrae superioris is mainly treated by frontalis suspension with autogenous fascia lata. In this study we evaluated the potential of an expanded polytetrafluoroethylene (ePTFE) soft tissue patch to function as a frontalis sling in 13 patients with ptosis palpebrae superioris. Functional and cosmetic results and the satisfaction of the patients were scored positive or negative and statistically compared with 13 patients in whom fascia lata was used. The mean follow-up was ten months. Although no complications occurred in either group the patients in the ePTFE group were less satisfied (p < 0.01) and showed inferior functional (p < 0.05) and cosmetic results (p < 0.01) as compared to the fascia lata group. Histological analysis of an explanted piece of ePTFE revealed that tissue ingrowth into the patch was lacking, which might have led to poor anchorage and subsequently a recurrence of the ptosis. We believe that ePTFE is not the material of first choice in frontalis suspension. PMID- 1284264 TI - Long-term experiences with the two-stage palatoplasty with regard to the development of maxillary arch. AB - From our data on 46 patients operated on by one surgeon in 1961 and 1962 who were regularly examined up to adulthood, it may be concluded that the growth results of the two-stage palatoplasty, when the second stage is done before the patient is 7 years of age, are almost identical to the results of one-stage palate repair performed at the age of 3 to 4 years. However, a greater orthodontic effort is needed to achieve a properly aligned dentoalveolar arch with the two-stage palatoplasty. PMID- 1284266 TI - Extracorporeal tissue transfer for salvage replantation. AB - The author reports the use of extracorporeal tissue transfer technique for salvaging severed digits of the hand which are unfit for replantation. The technique of extracorporeal tissue transfer has been reported by us earlier. In this paper its use has been extended for salvaging five non replantable digits in two cases. PMID- 1284265 TI - An extensive defect on the tibia covered by a free cross flap using m. latissimus dorsi. AB - Using a clinical case, the authors demonstrate the technique of covering an extensive tibial defect unmanageable, due to blood supply to the limb and extent of the defect, by conventional methods. The required amount of tissue was provided by a flap obtained from m. latissimus dorst transferred to the site of defect as a free cross flap. PMID- 1284267 TI - The neck collar--a treatment of hypertrophic burn scars of the neck region. A clinical study. AB - Hypertrophic burn scars of the neck region are disfiguring and cause functional disturbances such as itchiness, tenderness, blistering or even contractures. Since 1970 the Burns Unit in Copenhagen has treated hypertrophic scars of the neck with a special soft neck collar as a routine. This pressure treatment is controlled in the Jobst day-clinic by a team consisting of a surgeon, physiotherapist, occupational therapist and a nurse. The clinical results of 17 cases are reported and commented on. PMID- 1284268 TI - Growth and development of the face in complete unilateral cleft lip and palate during prepubertal and pubertal periods. AB - Roentgencephalometry was used for the assessment of the growth and development of the face during prepubertal and pubertal periods in children with complete unilateral cleft lip and palate treated with the same methods. The first series included 16 boys and 15 girls, the second series consisted of 15 boys and 15 girls examined repeatedly at the beginning and at the end of the follow-up period. There were no definite differences in the growth rate of the face between the two periods of age. Therefore, the deterioration of overjet during puberty could be due to the depletion of the compensation and adaptation mechanisms after the previous orthodontic treatment rather than to the enhanced growth rate. As compared to other facial dimensions a lower growth rate showed during both periods the length of the anterior base, the depth of the maxilla and in particular the height of the upper lip. Developmental changes of variables of shape and position proceeded similarly during both periods of age. An exception represented the rotation of the mandible and the inclination of upper incisors. During the prepubertal period the lower jaw showed a very slight posterior rotation, while during puberty an anterior growth rotation was present. A rapid improvement of the proclination of upper incisors was attained only during the prepubertal period. It was accompanied by an improvement of overjet. However, during the period of puberty there was a renewed deterioration of overjet. A marked retrusion of the maxilla developed already in the prepubertal period. During both periods occurred an identical impairment of sagittal jaw relations and of the upper lip prominence, accompanied by a flattening of the facial profile and reduction of the nasolabial angle. The prominence of the nose increased, the angle of the cranial base remained unchanged. Intersexual differences were not demonstrated in any studied characteristics. PMID- 1284269 TI - Ethical problems in burn injury in the past decade. AB - As a result of the increasing numbers of disasters and constant advances in medical care technology allowing survival of critically ill patients by using an interdisciplinary approach to comprehensive therapy, the past decade has seen the emergence of ethical problems related to burn injury. The study discusses the issue of sorting out patients from the point of view of providing emergency care and transport as well as from the point of view of psychologic care and palliative therapy. The quality of life and prolonged suffering of elderly individuals is another major issue as well as, last but not least, ethical and moral obstacles encountered in clinical research carried out in the critically ill where the potential of misuse is greater than in other groups of patients. The role played by ethical committees and by integrity of the research project coordinator are highlighted. PMID- 1284271 TI - Compendium of position statements on the nurse's role in end-of-life decisions. American Nurses Association Center for Ethics and Human Rights Task Force on the nurse's role in end-of-life decisions. PMID- 1284270 TI - The use of ozonotherapy in the nose correction operations. AB - Positive results of application of ozonotherapy in rhinoplasty are described. 25 patients were administered ozone intravenously for 3 days prior to operation and days post-operatively, resulting in a significant reduction in post-operative complications duration as compared with the control group consisting of 20 patients who were not administered ozonotherapy. PMID- 1284272 TI - [Chromosomal determinant of Streptomyces hygroscopicus with positive influence on resistance to bialaphos controlled by the bar gene]. AB - Streptomyces hygroscopicus ATCC21705 is an organism producing bialaphos, a promising ecologically safe antibiotic of peptide nature. An unknown determinant was cloned within the 1.4-kb SsH fragment of chromosomal DNA of S. hygroscopicus. Its presence along with the bar gene in the hybrid plasmid PVGB21 increased expression of the phenotype resistance to bialaphos in the recipient strain of S. lividans TK 64. Plasmid PVG B22 carrying the isolated SsH fragment did not provide resistance to the antibiotic. Transcription from the cloned fragment was revealed by RNA-DNA hybridization. It was shown that the cloned determinant had a positive action on bar gene transcription correlating with a significant increase in the activity of N-acetyltransferase in the mycelium of the transformant pVG B21. PMID- 1284273 TI - RNase protection assays and RNA gel blots: a direct comparison of sensitivity. AB - RNase protection assays are commonly thought to be a more sensitive means of detecting and quantitating specific mRNAs than are RNA gel blots (Northern blots). We have directly compared the sensitivity of these two approaches by assaying for known amounts of in vitro synthesized beta-glucuronidase mRNA. With the probes and protocols employed here, the ability to detect a specific mRNA was similar whether RNase protection or RNA gel blot analyses were performed. PMID- 1284274 TI - Direct reverse transcription--polymerase chain reaction from whole blood without RNA extraction. AB - A simple, fast, efficient method of direct reverse transcription-polymerase chain reaction (RT-PCR) from whole blood without RNA extraction is described. After the erythrocytes in a few microliters of fresh blood were destroyed and removed, the total RNA was released from the leukocytes by means of water treated with diethyl pyrocarbonate. The solution was used as RNA template and directly introduced in the RT-PCR. Following this method, which is called direct RT-PCR, three different cDNA fragments were successfully amplified with three different pairs of primers, respectively. Meanwhile, the direct RT-PCR was compared with the RT-PCR from the extracted total RNA template. The results showed no obvious difference. PMID- 1284275 TI - Three-dimensional structures of the human alpha 2-macroglobulin-methylamine and chymotrypsin complexes. AB - The three-dimensional structures of chymotrypsin- and methylamine-treated negatively stained human alpha 2-macroglobulin have been determined by weighted back projection from electron microscope data. Projections of the reconstructions show good concordance with two-dimensional averages of both stained and frozen hydrated molecules. The reconstructions reveal that the H-shaped front projection of the molecule is related to the smaller ellipsoidal end view by a rotation of 90 degrees about the crossbar (minor axis) of the H. This finding is in agreement with tilt studies. The reconstruction of the alpha 2-macroglobulin-methylamine reveals an hour-glass shaped void which is filled by the two proteinase molecules in the reconstruction of alpha 2-macroglobulin-chymotrypsin. Protein plugs which appear to block the exterior entrances to the cavity may function to prevent access of proteins to the encapsulated proteinase and serve to block its escape. Extensive thresholding of each reconstruction leaves a "backbone" consisting of two side-by-side rod-like structures, suggesting that this is the arrangement of the two protomeric units which form the molecule. Both structures show some departure from the expected symmetry. The asymmetries are robust features of the reconstructions and may reflect structurally asymmetric features of the transformation from the native to the chymotrypsin-treated form of the molecule. PMID- 1284276 TI - Frequency of common colds and serum levels of sICAM-1 (CD54), sLFA-3 (CD58) and sIL-2R (CD25). AB - Epidemiologic case-control studies have suggested an inverse relationship between past medical history of frequency of common colds and subsequent cancer risk for various sites. One hypothetical explanation for this finding may be that there are unknown differences in immune responsiveness between patients developing cancer and healthy individuals. The present study examines the relationship between the frequency of common colds and a) plasma levels of sICAM-1/CD54, sLFA 3/CD58 and sIL-2R/CD25 which are believed to modulate activation of immune responses, and b) cell-mediated immunity in vivo as determined by Multitest Merieux. The investigation was conducted as a correlation study amongst a healthy group of individuals from the general population in Germany. We found a statistically significant inverse relationship between frequency of common colds and levels of sCD58 and, partially, sCD54. No association was found between levels of sCD25 and results of Multitest Merieux. PMID- 1284277 TI - Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients. AB - Endotoxin (lipopolysaccharide, LPS) has the property of inducing tolerance to its own biological effects. This phenomenon has been extensively studied in animal models but only few studies exist on the regulation in humans. Here we describe experiments designed to determine the cytokine regulation and cellular changes in humans during induction of LPS tolerance after repeated LPS injections. Intravenous administration of purified LPS Salmonella abortus equi to cancer patients induces high amounts of circulating tumor necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte colony stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF). Repeated injections of LPS at daily intervals resulted in a marked downregulation of the cytokine response and in the case of TNF-alpha, IL-8, G-CSF, and M-CSF the cytokine response was reduced to baseline levels. In contrast, significant increases in serum IL-6 were detected up to day 5 of repeated LPS injections. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes, followed by a marked granulocytosis. The drop in WBCs remained unaltered throughout the 5 day course of repeated LPS injections whereas the granulocyte overshoot recovery diminished gradually. When PBMCs of the cancer patients were restimulated ex vivo a marked enhancement of the capacity to produce TNF-alpha, IL-113, and IL-6 occurred, which is in contrast to the decreasing TNF-alpha serum levels obtained in vivo. In parallel, a shift in monocyte subpopulations from CD14+/CD16- to CD14+/CD16+ cells was observed. The data provide evidence that different mechanisms are implicated in the cytokine downregulation following repeated LPS injections to cancer patients. Furthermore, PBMCs from LPS tolerant patients do not demonstrate a reduction in their capacity to produce cytokines. PMID- 1284278 TI - [A method for isolating a complex epoxide-containing antigen and its use for the diagnosis of allergic diseases]. AB - Specific complex antigen, based on human serum albumin and epichlorhydrine was proved to be useful in the diagnosis of individual hypersensitivity to the epoxide pitches and epichlorhydrine. Lymphocytes' blast transformation with 3H timidine was proved to be the most sensitive reaction in the use of specific complex antigen during the diagnosis. The stated immune reaction can be used for the diagnosis of allergy before the clinical manifestations. PMID- 1284279 TI - [The comparative characteristics of the cytochemical indices of the peripheral blood neutrophils in the separate administration of organochlorine and organophosphate pesticides against a background of dynamic loading with different intensities]. AB - Cytochemical parameters of peripheral neutrophils were studied in the experimental pattern of combined action of chlorine and phosphorus containing organic pesticides and different levels of dynamic physical strain. Studies revealed the protective effect of the minimal physical strain and aggravating effect of the moderate and maximal strain leading to the depressed aerobic oxidation and increased anaerobic glycolysis. PMID- 1284280 TI - A pilot study of ChlOPhEPP-B--a weekly regimen for patients with untreated advanced or recurrent Hodgkin's disease. AB - Twenty-five patients with either previously untreated advanced Hodgkin's disease (HD) or with relapsed disease were treated with an intensive weekly chemotherapy regimen (ChlOPhEPP-B) in which the myelosuppressive combinations of epirubicin and chlorambucil, and procarbazine and etoposide alternated at two-week intervals, interspersed with vincristine and prednisolone and then vincristine, prednisolone and bleomycin in a four-week cycle. Of the previously untreated patients (n = 14), 12 (86 per cent) showed a complete response (CR); in the previously treated patients (n = 11), CR was achieved in five (46 per cent). Toxicity was predictable and not evidently more severe than with more standard regimens. Neutropenia leading to treatment delay and/or dose reduction was seen in 11 patients (44 per cent) but severe neutropenia (WHO grade 4) was documented in only six patients (24 per cent) for a cumulative total of nine treatment weeks (1.8 per cent of the total treatment time). Dose reductions for neutropenia were applied in relation to 11 of the 379 weekly treatment points (2.9 per cent). Delays in treatment, for any reason, averaged 3.65 weeks per patient. The study demonstrated the feasibility of a more intensive weekly multidrug schedule. This approach may be applicable in the treatment of advanced HD and represents a further option in the strategy of treating relapsed disease. PMID- 1284281 TI - A tiaramide derivative, 5-chloro-3-(4 hydroxypiperadinocarbonylmethyl)benzothiazoline-2-one (HPR-611), a potent inhibitor of anaphylactic chemical mediator release--a distinctive feature from disodium cromoglycate. AB - Effects of a tiaramide derivative, 5-chloro-3-(4 hydroxypiperadinocarbonylmethyl)benzothiazoline++ +-2-one (HPR-611), on anaphylactic chemical mediator release from rat peritoneal exudate cells (RPEC), guinea pig lung fragments (GPLF) and human lung fragments (HLF) were investigated in comparison with those of tiaramide and disodium cromoglycate (DSCG). HPR-611 at 10(-6) - 10(-4) g/ml showed a concentration-dependent inhibition of the histamine release from RPEC regardless of its pretreatment time. Tiaramide also inhibited the release with slightly less potency than HPR-611. The treatment of DSCG 1 min before antigen challenge markedly prevented the release but the inhibitory potency was clearly deteriorated by prolongation of the pretreatment time. Tiaramide tended to influence the anaphylactic release of histamine from GPLF with only 20% inhibition of the release at either 10(-5) or 10(-4) g/ml, whereas HPR-611 at 10(-5) and 10(-4) g/ml significantly suppressed the release in a concentration-dependent fashion. DSCG was not effective on that even at higher concentrations. Anaphylactic release of not only histamine but also immunoreactive leukotriene B4 (i-LTB4) and i-LTC4 from HLF was markedly inhibited by 10(-8) - 10(-4) g/ml of HPR-611. Tiaramide inhibited the release to a somewhat less extent than HPR-611, while nominal or no inhibitions by DSCG were found. From these results, it is clearly apparent that anti-allergic actions of HPR-611 are quite different from those of DSCG. PMID- 1284282 TI - Prostate adenocarcinoma using Gleason scores correlates with prostate-specific antigen and prostate acid phosphatase measurements. AB - To evaluate a relationship between Gleason scores of histopathology of prostate carcinoma and concurrent serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) values, 65 men with prostate carcinoma were studied. These patients' cumulative Gleason scores were obtained by totaling the primary and secondary patterns, resulting in two groups: 42 patients received high (6-10) and 23 received low (2-5) Gleason scores. Serum PSA and PAP values were measured by radioimmunometric assay 1 to 7 days before surgical procedures or biopsy for prostate carcinoma. Mean serum PSA for patients in the high Gleason score group was 134.39 ng/mL (normal range: 0 to 4), and the mean serum PSA for patients in the low Gleason score group was 23.62 ng/mL. Mean serum PAP for patients with high scores was 28.08 ng/mL (normal range: 0 to 5), and the mean serum PAP for patients with low scores was 18.19 ng/mL. Patients with high Gleason scores showed significantly greater elevation of serum PSA than those with low Gleason scores (P = .047), using two samples to test for groups having unequal variants. Prostate acid phosphatase levels of patients with high scores were not significantly higher than the levels in patients with low scores (P = .60). These results indicate that PSA levels but not PAP levels correlate with Gleason scores. PMID- 1284283 TI - Effect of neutralizing monoclonal antibodies on Hantaan virus infection of the macrophage P388D1 cell line. AB - The effect of neutralizing monoclonal antibodies (N MAbs) on Hantaan virus infection of macrophages was investigated using P388D1 cells, a murine macrophage cell line. MAbs to the G1 protein (G1b) and the G2 protein (G2a and G2c) neutralized viral infectivity in P388D1 cells. N MAbs to G1b showed much higher neutralizing potency than those to G2a and G2c. With each N MAbs, two distinct effects were observed: neutralization of viral infectivity occurring at high concentrations and enhancement of that at low concentrations. Non-neutralizing MAbs, on the other hand, showed only enhancement of viral infectivity even at high concentrations without any inhibitory effects. The Fab fragments of N MAbs showed neither neutralizing nor enhancing activities. However, when the virus-Fab complexes were reacted with the anti-Fab antibodies, both neutralization and enhancement of viral infectivity were restored depending on the dose of Fab fragments. These results indicate that Hantaan virus infection of P388D1 cells is mediated by the Fc portion of the antibodies and neutralization is dependent on the concentration of N antibodies bound bivalently to the neutralization site on the virion. PMID- 1284284 TI - Differential distribution of a carbohydrate epitope (Y) on human salivary gland cell membranes. AB - Monoclonal antibody 303 (mAb 303) reacts with the high molecular weight agglutinin present in human saliva. Its reactivity is periodate sensitive, and it has been shown to recognize the Y epitope. Immunogold labeling of thin sections of human parotid and submandibular glands with mAb 303 showed reactivity in secretory granules of serous acinar, intercalated and striated duct cells (Takano et al., 1988). We now report that the apical and basolateral membranes of salivary acinar and duct cells are labeled by mAb 303, but not myoepithelial cells, endothelial cells and other mesenchymal cells. Gold particles were confined to acinar and duct cell membranes even when myoepithelial cells were directly adjacent, suggesting that the epitope resides on a membrane glycoprotein and that the label does not represent secreted agglutinin bound to the cell surface. Although myoepithelial cells are thought to differentiate from epithelial stem cells, the present results indicate that substantial compositional differences exist between the membranes of myoepithelial cells and other salivary parenchymal cells. Earlier studies also showed that mAb 303 labels normal pancreatic acinar cells and certain salivary (pleomorphic adenoma) and mammary (lactating adenoma) tumors (Bogert et al., 1988). This antibody thus may be a useful reagent for characterizing the origin of exocrine gland-derived cell cultures and neoplastic cells. Further, localization studies may provide insight into the role of the Lewis blood group-related epitope in secretory cells. PMID- 1284285 TI - Viral inhibition of the interferon system. AB - In response to interferon (IFN), cells develop an antiviral state in which the replication of a wide spectrum of RNA and DNA viruses is inhibited. Viruses have evolved a variety of mechanisms to inhibit the production and action of the interferons. Interferon action may be blocked by inhibition of the post-receptor signalling pathway, which prevents the expression of a number of proteins with antiviral properties. Other viruses prevent the action of specific, interferon induced antiviral systems. In particular, the action of the dsRNA-dependent protein kinase (DAI) is inhibited by a variety of different viruses, indicating the fundamental importance of this enzyme to the antiviral response. PMID- 1284286 TI - Specific interactions of pancreatic amylase at acidic pH. Amylase and the major protein of the zymogen granule membrane (GP-2) bind to immobilized or polymerized amylase. AB - Regulated secretory proteins are thought to be sorted in the trans-Golgi network towards the secretory granule via acidic aggregation. In the exocrine pancreas, amylase is one of the major zymogens. It is a basic protein of pI 8.6 and does not precipitate in acidic conditions. To identify the mechanism by which amylase aggregates in the acidic cisternae of the pancreatic trans-Golgi network, we have developed an in vitro model in which amylase was fixed to plastic microtiter plates. The fixed amylase was probed with two ligands: amylase itself and GP-2, the major protein of the zymogen granule membrane. Biotinylated amylase bound to fixed amylase in a strict pH-dependent manner with optimal binding between pH 5.0 and 5.7. The affinity of binding was in the nanogram range (Kd approximately 20.0 ng/mL) at pH 5.5. Acid binding of amylase was not reversible by incubation at neutral pH, nor could it be displaced by native amylase. GP-2 binding to fixed amylase was also pH dependent with optimal binding between pH 5.0 and 5.7. As for amylase, it was not reversible by incubation at neutral pH. GP-2 binding sites on fixed amylase appeared to be different from those of biotinylated amylase. While native and biotinylated amylase did not bind to GP-2, polymerized amylase precipitated GP-2 at acidic pH. Taken together these data suggest that slight modifications are sufficient to reveal on the amylase molecule binding sites for GP-2 and for amylase itself. These new binding capacities acquired at acidic pH could be involved in the cascade of reactions that lead to the in vivo formation of the immature secretory granule. PMID- 1284287 TI - Pharmacological doses of insulin equalize insulin receptor phosphotyrosine content but not tyrosine kinase activity in plasmalemmal and endosomal membranes. AB - Following insulin administration to intact rats, the insulin receptor kinase activity of subsequently isolated cell fractions was significantly augmented. Of interest was the observation that the endosomal insulin receptor tyrosine kinase displayed four- to six-fold greater autophosphorylation activity than that of plasma membrane. Surprisingly, the endosomal insulin receptor tyrosine kinase displayed a decrease in beta-subunit phosphotyrosine content compared with that seen in the plasma membrane. These observations prompted the suggestion that insulin receptor tyrosine kinase phosphotyrosine dephosphorylation mediated by an endosome-specific phosphotyrosine phosphatase(s) yields activation of the endosomal insulin receptor tyrosine kinase. In a previous study we examined the effect of subsaturating doses of injected insulin. In this work we evaluated insulin receptor tyrosine kinase activity and phosphotyrosine content in plasma membrane and endosomes after a receptor-saturating pharmacological dose of insulin (150 micrograms/100 g body weight). At this dose the phosphotyrosine content per receptor was reduced compared with that seen earlier at insulin doses of 1.5 and 15 micrograms/100 g body weight. Endosomal insulin receptor tyrosine kinase was greater than that seen at the lower nonsaturating insulin doses. Furthermore, endosomal insulin receptor tyrosine kinase activity exceeded that of the plasma membrane, despite retaining about the same phosphotyrosine content per receptor. These data are consistent with the view that insulin receptor tyrosine kinase activity may be regulated by a particular pattern of phosphotyrosine content on the beta-subunit wherein both activating and inhibitory phosphotyrosine residues play a role. PMID- 1284288 TI - Modulation of cytokeratin and actin gene expression and fibrillar organization in cultured rat hepatocytes. AB - Intermediate filaments of rat hepatocytes are composed of cytokeratins 8 and 18 (CK8 and CK18, respectively). Recent work from our laboratory has indicated a close relationship between the synthesis of these cytokeratins, their organization into intermediate filaments, and the promotion of growth and differentiation of cultured rat hepatocytes by insulin, epidermal growth factor, and dexamethasone. In the present study, we examined the mRNA expression, level of protein synthesis, and fibrillar distribution of cytokeratins 8 and 18 and actin in hepatocytes, isolated from normal and dexamethasone-injected rats and cultured as monolayers or spheroids in the presence of insulin, or from normal rat hepatocytes, cultured as monolayers in the presence of dexamethasone, insulin, and dimethyl sulfoxide. The CK8 mRNA level was lower in hepatocytes isolated from noninjected rats and cultured as either monolayers or spheroids, than in those from dexamethasone-injected rats. However, the CK18 mRNA level varied in a manner that was different from that of CK8 mRNA, showing that the modes of expression of the two genes were independent. The various changes in hepatocyte culture conditions led to variations in albumin mRNA levels that largely followed those observed in CK8 mRNA levels. In the case of actin, the amount of mRNAs varied from relatively high levels in hepatocyte monolayers to extremely low levels in hepatocyte spheroids, even though in both cases the cells were isolated from dexamethasone-injected rats. These changes in mRNA levels did not necessarily correlate with changes in the synthesis of cytokeratins 8 and 18, and actin. Changes in culture conditions induced a major reorganization in the distribution of cytokeratin intermediate filaments and actin filament between the region near the surface membrane and the cytoplasm. The most divergent patterns in cytokeratin intermediate filaments and actin filament distributions were observed between hepatocytes cultured as spheroidal aggregates and as monolayers in the presence of dimethyl sulfoxide. The former condition resulted in patterns of cytokeratin and actin gene expression and fibrillar organization that best matched those in situ. In the latter condition, inappropriate patterns were obtained, in spite of the fact that dimethyl sulfoxide treated hepatocytes are known to exhibit survival and functional activities equivalent to that of hepatocyte spheroids. These results demonstrate for the first time that the survival and functional activity (i.e., albumin production) of rat hepatocytes in vitro is not necessarily correlated with a particular pattern of cytokeratin and actin gene expression and fibrillar arrangement. PMID- 1284289 TI - The production of hybridoma cell line secreting monoclonal antibodies against Xanthomonas campestris pv. oryzae and its application in the classification of strains. AB - By the fusion of mouse myeloma cells (SP2/0-Ag14) and spleen cells derived from BALB/c mice immunized with the preparation of Xanthomonas campestris pv. oryzae Ks-6-6, Os-213, Yz-32 and Yz-24, we obtained 12 hybridoma cell lines secreting monoclonal antibodies. None of the McAbs cross-reacted with the other varieties of plant pathogenetic and non-pathogenetic bacteria. The McAbs could distinguish three variant serotypes of strains. Antibody titers of ascites were about 1:10(3) 1:10(6) when measured by ELISA method. The McAbs could differentiate 6 epitopes. Based on the epitopes, the 63 strains of X. campestris pv. oryzae we collected were grouped into nine groups. PMID- 1284290 TI - Overexpression of rnc gene and purification of RNaseIII. AB - The reason for low content of RNaseIII in E. coli is that RNaseIII has a negative feedback action on its own synthesis by cutting off the transcripts of its own gene, rnc, at 5'-terminal. On this basis, the scheme for overproduction of RNaseIII was designed. The 5'-flanking sequence of rnc gene transcribing to form a secondary structure which could be degraded by RNaseIII was removed, and the whole coding sequence, including the translational initiation signal, was reserved and put under the control of lambda PL promoter. The constructed plasmid pCR21, which contain the recombined rnc gene, overproduced RNaseIII, which covered over 65% of the total cell protein and formed inclusive bodies in E. coli after induction at 42 degrees C. By using the characteristics of solubility of the protein, electrophoretic pure RNaseIII was obtained with a simple procedure, including lysis of the bacterial cells, washing precipitates of the lysate repeatedly at low temperature and low salt concentration, and dissolving and passing through Q-Sepharose FF column in high salt concentration at room temperature. The yield of purified RNaseIII was 10-12 mg per 100 ml culture, and lambda sib transcripts were cut at special sites. RNaseIII possessing the activity of binding ATP is reported. PMID- 1284291 TI - [Structural and functional properties of type A GABA receptors in the central nervous system of mammals]. PMID- 1284292 TI - Isolation of 2 novel RFLP markers and their localization at 2q35 by microdissection and subsequent enzymatic amplification. AB - We previously constructed a chromosome 2q-specific genomic library and isolated a number of microclones. In the present study, we first analyzed with Southern hybridization whether any of the microclones represent restriction fragment length polymorphisms (RFLPs), and then tried to map RFLP markers physically, using the recently developed chromosome microdissection/enzymatic amplification method. Of 13 clones analyzed, two were RFLP markers; a clone, pM2C83, showed a four-allele MspI RFLP, and the other, pM2C8, a two-allele RsaI RFLP. In order to assign the two polymorphic markers, two chromosomal segments, 2q32-q35 and 2q35 qter, on the chromosome 2 from a karyotypically normal person were microdissected, and the DNA from each segment was amplified with the polymerase chain reaction (PCR) using marker sequence-specific primers. With this method, both of the clones were assigned to 2q35. These two RFLP markers must be useful for linkage analysis of genetic diseases whose loci are at around 2q35. PMID- 1284293 TI - Parent-specific expression of a human keratin 18/beta-galactosidase fusion gene in transgenic mice. AB - Insertion of a human keratin 18 (K18)-bacterial beta-galactosidase (LacZ) fusion gene into mice has led to a unique transgenic line in which expression of the transgene is subject to unusual germ line-specific, genomic imprinting effects. Fetal expression of the LacZ reporter gene depends on the gender of the transmitting parent, with appropriate expression in liver after maternal inheritance, and ectopic expression in retina and mesodermal tissues after paternal inheritance. This tissue-specific imprinting pattern is superimposed upon a basic expression pattern which is unaffected by parental inheritance. Insertion of the transgene has led to a recessive-lethal phenotype, with no parent-of-origin effects on viability, suggesting that the transgene has not inserted into an imprinted region of the genome. HpaII and HhaI methylation sensitive restriction sites within the bacterial LacZ reporter gene are completely methylated when activity of the maternally inherited transgene is detected in the fetal liver, and not methylated when the paternally inherited transgene is silent. Thus DNA methylation of LacZ is correlated with maternal inheritance and may be implicated in the genomic imprinting mechanism as others have suggested. However, in contrast to the commonly found correlation of expression and low DNA methylation, the LacZ gene was expressed in fetal liver when fully methylated. This result may imply the existence of negative regulatory activities that recognize the unmethylated LacZ gene. PMID- 1284294 TI - Immunoperoxidase labelling of previously stained tissue sections: application in oral histopathology. AB - We have investigated by the avidin-biotin peroxidase technique a wide variety of recognized cellular antigens in paraffin sections of both normal and pathological material which have been previously stained with hematoxylin and eosin. The intensity of peroxidase reaction was adequate to permit the diagnosis and the background of the immunoreaction minimal. This technique therefore, appears useful either for retrospective analysis of cellular antigens or when limited unstained material is available. PMID- 1284295 TI - [Epidermoid carcinoma of the oral cavity: a histopathological study of 85 cases]. AB - In 85 cases of intraoral squamous cell carcinoma we have carried out a descriptive and statistical analysis of 8 parameters or morphological aspects: structural growth pattern, degree of keratinization, differentiation or similarity, nuclear pleomorphism, frequency of mitoses, inflammatory response, number of eosinophils and vascular invasion. We have found that in 65% of the cases there was a cord type growth pattern, and 51% evidenced a maximum degree of keratinization. The neoplastic cells were characterized by a moderate differentiation and pleomorphism, 69% and 73% respectively, there being 1-3 mitoses/8 fields in 54% of the cases. We did not find very marked differences between degrees 1, 2, and 3 of inflammatory response (39%, 25%, 33% respectively). We observed vascular invasion in only 8.5% of the cases. The average value of intratumoral and peritumoral eosinophils was 18 and 37. PMID- 1284296 TI - Trying to overcome residual disease after bone marrow transplantation for hematologic malignancies. AB - Relapse after marrow transplantation occurs despite total body irradiation and high doses of chemotherapy used to prepare the recipient. Recurrence rate is particularly high after autologous transplantation. In order to eliminate minimal residual disease persistent after marrow grafting, immunotherapy is currently being explored as a treatment modality that is non-cross-reactive with radiation and chemotherapy. This review describes first clinical results on the use of interferons and interleukin-2 in marrow transplant recipients as well as attempts to induce graft-versus-leukemia effects. PMID- 1284297 TI - [Slowly progressive dysarthria and impaired language function--a case report]. AB - A 68-year-old right-handed woman was admitted to Tokyo Metropolitan Geriatric Hospital because of slowly progressive dysarthria and writing disability over 2 year period. On admission, severe dysarthria was observed, but no dysphagia. The dysarthria mostly resembled a type of pseudobulbar palsy, although it was associated with effortful speech production. An oro-facial apraxia was also found. She could name objects, and could understand spoken words correctly. Examination using the Western Aphasia Battery showed diminution of word fluency, impaired repetition and perseveration and writing errors. On the Wechsler Adult Intelligence Scale-R verbal IQ was 100 and performance IQ was 87. These scores did not suggest any significant degree of general intellectual deterioration. Wisconsin card sorting test disclosed mild frontal dysfunction. Magnetic resonance imaging showed cortical atrophy in the bilateral frontal and temporal lobes. Measurements of regional cerebral metabolic rate by 18F-FDG-PET demonstrated decreased uptake in the latero-dorso-inferior area of the bilateral frontal lobes, especially on the left side. The present case showed slowly progressive dysarthria and progressive aphasia without generalized dementia, and without typical aphasia. These symptoms are speculated to be related to the atrophy in the bilateral frontal and temporal lobes shown by MRI and the decreased metabolic rate in the left dominant bilateral frontal lobes on PET study. The pathologic process responsible for these lesions remains obscure. PMID- 1284298 TI - [Gene expression regulation. Principles and methods]. PMID- 1284299 TI - Endothelin-1 inhibits the vasodilation induced by substance P in isolated porcine ophthalmic artery. AB - The vasoconstrictor effect of endothelin-1 is long-lasting and slow in onset, suggesting that this peptide may be involved with long-term vascular responses. Substance P, a quick-acting, vasodilatory tachykinin present in sensory nerves, may be released by trigeminal fibres and thereby participate in the regulation of vascular tone in the head. Given the potential role of vasoregulatory peptides in the ocular-forehead circulation in the pathophysiology of vascular headaches, the interactions between substance P and endothelin-1 over time were studied in isolated porcine ophthalmic artery. Substance P-induced relaxation of precontracted artery segments was significantly diminished by endothelin-1, despite the fact that endothelin-1 itself had no further significant contractile effect on these arteries. It is also noteworthy that the observed reduction of substance P-induced relaxation occurred much more rapidly than the onset of endothelin-1-induced contraction in relaxed porcine ophthalmic artery. The results suggest an inhibitory synergism between endothelin-1 and substance P in this vascular bed. PMID- 1284300 TI - [Comparison between nuclear DNA and histologic grade of prostatic carcinoma]. AB - DNA nuclear ploidy determined by flow cytometry was evaluated from prostate tissue in 51 patients with prostatic cancer who had undergone radical prostatectomy. DNA ploidy pattern was diploid in 46% and aneuploid in 54% of tumors. DNA ploidy was compared to histological tumor grading. 92 Aneuploidy was found in 0% of the tumors with Gleason score between 2 and 4 in 62% between 5 and 7 and in 50% between 8 and 10. Our results suggest there is no relationship between the two parameters. PMID- 1284301 TI - Conversion of Mobitz type II AV block to 1:1 AV conduction by premature ventricular beats. AB - Preliminary experiments in a canine model of Mobitz type II atrioventricular (AV) block showed improvement of conduction after premature ventricular beats. In this investigation, the authors studied the mechanism(s) responsible for this response. In vivo studies were performed in 16 anesthetized dogs. Block was induced by ischemia after septal artery occlusion or by mechanical trauma. Two pairs of plunge electrodes were inserted in the proximal and distal His bundle. An electrode catheter was positioned at the level of the aortic root to provide an overall view of His bundle activation. Bipolar pacing was performed from the high right atrium, right ventricular outflow tract, and proximal and distal His bundle. Infra-nodal 2:1 AV block was consistently induced at an atrial rate of 238 +/- 21 beats/min. In 15 dogs a narrow time window (10-60 ms; mean, 32 +/- 6 ms) was found during which premature beats resulted in transient (2-11 beats; n = 9) or persistent (n = 8) restoration of 1:1 AV conduction. Retrograde penetration of the site of block, that is, Hb, was found even when the anterograde impulse was blocked, demonstrating the asymmetric nature of anterograde versus retrograde conduction. In vitro studies were performed in the same hearts. Intracellular recordings were obtained in the damaged His bundle and proximal right bundle. The site of block showed frequent displacements along the bundle. The introduction of a retrograde stimulus during 2:1 block restored 1:1 anterograde conduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284302 TI - Structure of G-CSF: significance of the sugar chain. AB - 1. The carbohydrate chain protects rhG-CSF from polymerization and/or conformational alterations associated with physicochemical changes, elevation of pH or temperature fluctuations. 2. The carbohydrate chain of rhG-CSF prevents loss of its biological activity in normal human serum by inhibiting proteinase activity. 3. These facts indicate that the carbohydrate chain of rhG-CSF has a markedly important role in maintaining the stability of the protein itself as well as in effecting the exertion of its biological activity. PMID- 1284303 TI - Pathophysiological roles of G-CSF. PMID- 1284304 TI - Clinical use of recombinant human G-CSF. Aplastic anemia (AA) and myelodysplastic syndromes (MDS). PMID- 1284306 TI - Effects of granulocyte-colony-stimulating factor in neutropenic AIDS-patients. PMID- 1284305 TI - Recombinant granulocyte colony-stimulating factor (rG-CSF) in HIV patients with zidovudine related neutropenia. PMID- 1284307 TI - The clinical use of RHG-CSF for malignant lymphomas. PMID- 1284308 TI - A randomised vehicle controlled multicenter dose finding phase. II. Study of glycosylated rhuG-CSF in 121 patients after bone marrow transplantation. PMID- 1284309 TI - G-CSF mobilised progenitor cells in autologous transplantation: in vitro and in vivo aspects. AB - G-CSF administration leads to significant elevation in the levels of circulating progenitor cells. Infusion of these cells after high-dose chemotherapy is associated with accelerated platelet engraftment that has a considerable impact in shortening thrombocytopenia and reducing need for platelet transfusions. PMID- 1284310 TI - Inward rectification of acetylcholine-elicited currents in rat phaeochromocytoma cells. AB - 1. Currents elicited by acetylcholine (ACh) were studied in the rat phaeochromocytoma cell line, PC12, using patch-clamp techniques. 2. Whole-cell ACh-elicited currents are inwardly rectifying and intracellular Mg2+ can play a role in determining the extent of whole-cell current rectification. Increasing the intracellular Mg2+ concentration, [Mg2+]i, augmented the rectification. The effects of increased [Mg2+]i on the whole-cell current can be explained by the block of receptor channels by Mg2+. 3. In the nominal absence of internal divalent cations, however, a substantial degree of rectification remains. This rectification is probably not due to divalent cations, as buffering the external Mg2+ concentration to 50 microM and the internal concentration to nominally 0 Mg2+ did not reduce the rectification. The remanent rectification was not due to block by the main permeant cation, Na+. Using K+ or Cs+ as the main monovalent cation inside the cell did not diminish the rectification. Neither replacing the pH buffer, HEPES, with phosphate buffer nor increasing the intracellular pH removed the rectification. 4. For ACh receptor channels in excised patches, the voltage dependence of the probability of being open (Popen) stemmed mainly from the voltage dependence of the channel burst duration. The channel opening rate was relatively voltage independent. The weak voltage dependence displayed by the channel burst duration was insufficient to account for the reduced whole-cell outward current at positive potentials. The mean burst duration of the channel did not have a simple logarithmic relationship with voltage. 5. In the absence of intracellular Mg2+, the instantaneous current-voltage relationship for whole-cell currents was linear suggesting that the I-V relationship of single channels in perfused cells is linear and does not contribute to the rectification of the whole-cell current. 6. In perfused cells, receptor channels had a low steady state probability of being open at positive potentials compared to channels in excised patches. Voltage jumps to positive potentials revealed a process in perfused cells which could account for the low Popen. Relaxations of agonist induced current at +40 mV had a large, exponentially decaying component that quickly closed channels (rate constant, tau, approximately 400 microseconds). The mechanism responsible for this decay could explain the rectification that remains in the absence of intracellular divalent cations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284311 TI - Effect of nitro-L-arginine on endothelium-dependent hyperpolarizations and relaxations of pig coronary arteries. AB - 1. Endothelium-dependent relaxation is caused by an endothelium-derived relaxing factor (EDRF) identified as nitric oxide (NO). Our objective was to test whether one or several distinct endothelium-dependent relaxing factors exist. 2. In pig coronary arteries, a hyperpolarization accompanied by the relaxation caused by high concentrations of substance P (SP) and bradykinin (BK). 3. To examine the role played by nitric oxide and prostacyclin in the endothelium-dependent relaxations and hyperpolarizations caused by SP and BK on pig coronary arterial strips, the production of NO was inhibited by NG-nitro-L-arginine (L-NNA) and the production of prostacyclin was inhibited by indomethacin, while monitoring smooth muscle membrane potential and isometric tension. 4. Indomethacin had no effect on resting isometric tension nor on SP and BK relaxations of strips precontracted by prostaglandin F2 alpha. 5. L-NNA contracted arterial strips with intact endothelium, without changing the membrane potential of smooth muscles. 6. The inhibitor shifted to the right the concentration-response curve of kinins by 0.2 nM SP and 20 nM BK. It inhibited the maximal relaxations and hyperpolarizations by 30%. 7. The results show that, in pig coronary arteries, EDRF (NO) mainly controls the basal tension, whereas other factor(s) play(s) an important role in hyperpolarizations and relaxations caused by the kinins. PMID- 1284312 TI - Ca(2+)-activated and voltage-gated K+ currents in smooth muscle cells isolated from human mesenteric arteries. AB - 1. Smooth muscle cells were enzymatically isolated from arteries dissected from mesenteric fat removed from patients undergoing routine surgery. The whole-cell patch clamp technique was used to characterize the potassium (K+) currents and passive electrical properties of these cells, using high-K(+)-containing pipette solutions with either 0.2 mM EGTA or 10 mM EGTA and 10 mM BAPTA. 2. Cell capacitance, which is proportional to membrane surface area, was normally distributed around a value of 46 pF, and independent of artery size between 0.4 and 3.6 mm. The mean membrane potential measured under current clamp was -44.1 +/ 1.9 mV (n = 52). 3. Cells dialysed with 0.2 mM EGTA in order to weakly buffer intracellular Ca2+ demonstrated a noisy outward current with an apparent threshold near -30 mV, upon which were superimposed spontaneous transient outward currents (STOCs). In the presence, but not the absence, of extracellular Ca2+, this current was potentiated if the holding potential was depolarized into the voltage range between -40 and +50 mV. This potentiation had a bell-shaped potential dependency which reflected the activation of voltage-gated Ca2+ channels in these cells. 4. The noisy current was blocked by externally applied tetraethylammonium (the dissociation constant, Kd = 0.85 mM), as were STOCs. This current was also reduced by about 40% by 8 nM charybdotoxin, and was transiently potentiated by 10 mM caffeine. The characteristics of this current therefore suggested that it was carried by large-conductance Ca(2+)-activated K+ channels. 5. Dialysis of human mesenteric arterial cells with 10 mM EGTA and 10 mM BATPA was not able to completely suppress the Ca(2+)-activated current, and reduced by approximately 50% the amplitude of the outward current recorded at positive potentials. 6. Depolarization of strongly Ca(2+)-buffered cells in the presence of 30 mM TEA to block Ca(2+)-activated K+ channels revealed a residual outward current which had both transient and sustained components. These were blocked by 4-aminopyridine (4-AP) with a similar efficiency (Kd was 1.04 and 1.16 mM at +60 mV for transient and sustained current, respectively), but the voltage ranges over which they inactivated, and their rates of recovery from inactivation, were significantly different. 7. The transient and sustained currents had different sensitivities to external Ca2+ and Cd2+ ions. Ca2+ (5 mM) significantly reduced the amplitude and shifted the voltage dependency of inactivation of the transient but not the sustained component of the outward current. Cd2+ (0.2 mM) reduced the transient current by about 30% without affecting the sustained component amplitude.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284314 TI - [Serum lipoprotein (A) in patients with myocardial infarction and aortoarteritis]. AB - To elucidate the physiological role of lipoprotein (a), a new independent atherosclerosis risk factor, the levels of lipoprotein (a) and 5 proteins of an acute phase were measured in acute (myocardial infarction, n = 21) and chronic (non-specific aortoarteritis, n = 15) tissue lesions. Blood was taken for analysis from patients with myocardial infarction when they were admitted to hospital for anginal attacks and then 4 times during a month and from patients with aortoarteritis at the stage of exacerbation 1 month before and after therapy. The findings indicate that in acute and chronic tissue lesions, there is a change in blood lipoprotein (a) levels, which is largely similar to that in the levels of acute phase proteins. One cause of such changes may be an increase in the synthesis of apolipoprotein (a) that is identical to that of other glycoproteins--acute phase proteins--in the reaction of the acute phase and then in the regeneration of damaged tissues. PMID- 1284315 TI - [The role of neurotransmitters in psychiatric pathology]. PMID- 1284313 TI - A novel large-conductance Ca(2+)-activated potassium channel and current in nerve terminals of the rat neurohypophysis. AB - 1. Nerve terminals of the rat posterior pituitary were acutely dissociated and identified using a combination of morphological and immunohistochemical techniques. Terminal membrane currents were studied using the 'whole-cell' patch clamp technique and channels were studied using inside-out and outside-out patches. 2. In physiological solutions, but with 7 mM 4-aminopyridine (4-AP), depolarizing voltage clamp steps from different holding potentials (-90 or -50 mV) elicited a fast, inward current followed by a slow, sustained, outward current. This outward current did not appear to show any steady-state inactivation. 3. The threshold for activation of the outward current was -30 mV and the current-voltage relation was 'bell-shaped'. The amplitude increased with increasingly depolarized potential steps. The outward current reversal potential was measured using tail current analysis and was consistent with that of a potassium current. 4. The sustained potassium current was determined to be dependent on the concentration of intracellular calcium. Extracellular Cd2+ (80 microM), a calcium channel blocker, also reversibly abolished the outward current. 5. The current was delayed in onset and was sustained over the length of a 150 ms-duration depolarizing pulse. The outward current reached a peak plateau and then decayed slowly. The decay was fitted by a single exponential with a time constant of 9.0 +/- 2.2 s. The decay constants did not show a dependence on voltage but rather on intracellular Ca2+. The time course of recovery from this decay was complex with full recovery taking > 190 s. 6. 4-AP (7 mM), dendrotoxin (100 nM), apamin (40-80 nM), and charybdotoxin (10-100 nM) had no effect on the sustained outward current. In contrast Ba2+ (200 microM) and tetraethylammonium inhibited the current, the latter in a dose-dependent manner (apparent concentration giving 50% of maximal inhibition (IC50) = 0.51 mM). 7. The neurohypophysial terminal outward current recorded here corresponds most closely to a Ca(2+)-activated K+ current (IK(Ca)) and not to a delayed rectifier or IA like current. It also has properties different from that of the Ca(2+)-dependent outward current described in the magnocellular neuronal cell bodies of the hypothalamus. 8. A large conductance channel is often observed in isolated rat neurohypophysial nerve terminals. The channel had a unit conductance of 231 pS in symmetrical 150 mM K+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284316 TI - [Suicidal behavior: clinical considerations]. PMID- 1284317 TI - Reversal of hypotension induced by Vibrio vulnificus lipopolysaccharide in the rat by inhibition of nitric oxide synthase. AB - Intravenous infusion of Vibrio vulnificus lipopolysaccharide (LPS) (1 mg/kg body wt) in rats caused a dramatic drop in mean arterial pressure within 10 min and a further decline in mean arterial pressure and heart rate which lead to death between 25 and 70 min. Rats treated with LPS followed 10 min later by the intravenous infusion of NG-monomethyl-L-arginine (L-NMMA, 20 mg/kg body wt) showed an initial drop in mean arterial pressure owing to the LPS infusion, followed by a transient rise in mean arterial pressure which lasted for approximately 40 min after the infusion of L-NMMA. The pressure values then remained level for at least 150 min post-LPS infusion. Control rats treated with equivalent volumes of saline infusion showed stable values of mean arterial pressure and heart rate. Additional control rats receiving L-NMMA alone showed the transient rise in mean arterial pressure, followed by a return to the baseline values. The results indicate that the symptoms of endotoxic shock resulting from V. vulnificus LPS may result in part from the stimulation of the activity of nitric oxide synthase. Inhibition of nitric oxide synthase by L-NMMA is a possible treatment for toxic shock induced by V. vulnificus. PMID- 1284318 TI - [Pneumocystis carinii pneumonia: laboratory diagnosis]. AB - We worked with 51 samples, 7 bronchoalveolar lavages (BAL) and 44 sputa (S) of 31 AIDS patients with clinical and radiographic symptoms compatible with Pneumocystis pneumonia. With the aim of finding a specific sensitive methodology for the diagnosis of Pneumocystis carinii, we evaluated 4 coloration techniques (silver methenamine, its modification without gold chloride, toluidine blue and Giemsa). 35% of the patients studied were positive. P. carinii were observed in 18% of the 44 sputa. We observed that the analysis of a single sputum sample (S) has a very low sensitivity and that the processing of two or more samples is necessary since only one of the 14 patients who had sent a single sample was found P. carinii positive, while in the remaining ten who had sent more than one (S) sample, the microorganism was detected in 50%. 4 of the 7 BAL were positive. 4 BAL were preceded by the analysis of an (S) sample: in two cases the results were negative while BAL allowed us to make the diagnosis, thus demonstrating its greater efficacy. To enhance sensitivity each sample was centrifuged until exhaustion and 10 slides were prepared for coloration with the final sediment. The four techniques employed were specific and all the Pneumocystis pneumonia patients responded to the treatment. Silver methenamine, its modification without gold chloride, and toluidine blue were very sensitive, in contrast to of Giemsa. The stain to be chosen is either silver methenamine, or its modification, because both achieve the best contrast, allowing optimum P. carinii identification. We suggest the implementation of some of these techniques in laboratory routine. PMID- 1284319 TI - The prevalence of the indirect hemagglutination test for melioidosis in children in an endemic area. AB - The indirect hemaglutination test for melioidosis was studied in 295 children who live in the northeastern part of Thailand. Sixty-seven children (22.7%) were healthy children who came to the well baby clinic. Two hundred and twenty-eight children (77.3%) came to the hospital because of some illnesses other than melioidosis. Eighty-three percent of the children had an IHA titer of at least 1:10 or greater. Twenty-two percent had an IHA titer of 1:80 or greater. The prevalence of positive IHA titer and the mean titer were higher in the older age group. The age of children should be considered when interpreting IHA titer for milioidosis. PMID- 1284320 TI - Experimental omento-myelo-synangiosis. AB - In 18 cats the omentum was mobilized, transposed, and placed directly upon the pia mater of the spinal cord. Within 2 months, vascular anastomoses developed at the omento-spinal cord interface and, as demonstrated by India ink perfusion, communicated widely with the cord's intramedullary vessels. Light and scanning electron microscopy (SEM) of the interface revealed the development of a "fibrous coat" of Goldsmith in continuity with the edges of the dura mater. It consisted mainly of a matrix of collagen fiber and fibroblasts, well vascularized with sinusoids, capillaries, arterioles and venules. The sinusoids, as identified by SEM, were present in both the fibrous coat and adjacent omentum, were lined with attenuated endothelium, and had multiple communications. The possible significance of the sinusoidal formation is discussed in this report. PMID- 1284321 TI - Study of bovine herpesvirus type 1 strains with monoclonal antibodies. AB - Fourteen strains of bovine herpesvirus type 1 (BHV-1, IBRV) representing all three groups of BHV-1 (BHV-1.1, BHV-1.2, BHV-1.3) were studied by ELISA using 106 monoclonal antibodies (Mabs) produced against BHV-1. On the basis of the ELISA, the Mabs could be divided into three groups. The first group (40 Mabs, 38%) reacted with all strains, the second group (43 Mabs, 41%) with the respiratory and genital strains (BHV-1.1 and BHV-1.2) while the third group (23 Mabs, 22%) only with the respiratory strains. Only 5 out of the antibodies neutralized respiratory and genital strains, and none of them neutralized the encephalitogenic strains (1.3). Three Mabs selected from each of the 3 groups, and the above five neutralizing strains were studied by Western blot. Antibodies of groups 1 and 3, and two neutralizing antibodies bound to a 90k protein (gpIII), whereas members of group 2 and 3 neutralizing antibodies reacted with a 74k and a 130k protein (both gpl). The results indicate that reactivity with monoclonal antibodies is as suitable for the classification of BHV-1 strains as is restriction endonuclease (RE) analysis but it cannot distinguish between subgroups within the groups. PMID- 1284322 TI - [Cardiovascular complications of interferon]. AB - Interferon, a fairly recent drug, is used in some cancers and other diseases. The adverse effects include cardiotoxicity which was recognized from phase-I trials. Some of these complications are very common and not serious at the dose levels administered: transient hypotension at the beginning of the treatment, atrial extrasystole. Other effects are less common and not dangerous: low-level conduction impairment or reversible hypertension as the authors recalled. There are also a much more serious forms of toxicity which may be life-threatening, one of which seems to be dose-dependent and consists of the onset of cardiomyopathy, which is usually reversible when treatment is stopped, the other is uncontrollable and usually occurs in high-risk cardiac patients from the first few injections and results in sudden death induced by acute coronary artery failure and/or serious ventricular arrhythmia. The physiopathology of this cardiotoxicity remains unknown, but as it is known to exist, rigorous cardiological monitoring of all patients receiving this treatment is necessary. PMID- 1284323 TI - Investigation of the solid- and solution-phase binding reactivities of continuous epitopes recognized by polyclonal guinea-pig anti-recombinant bovine growth hormone antisera. AB - We have used the technique of multiple pin peptide synthesis to identify three major continuous epitopes in the recombinant bovine (rb) GH molecule. We have synthesized these peptides, residues 24-40, 139-152 and 179-189, as N-terminally acetylated, C-terminal amides and confirmed their reactivity in a standard solid phase ELISA. Subsequently, for epitope 139-152, we have synthesized a peptide affinity column and used this to isolate antibodies with this epitope specificity from whole antiserum. In addition, we demonstrate that under native conditions in a liquid phase RIA, these antibodies will precipitate [125I]rbGH. Further, peptide 139-152 itself also cross-reacts in an rbGH RIA inhibiting binding by up to 20%. Our data suggest that during the immune response to rbGH in guinea-pigs a substantial part of the B-cell response is directed to the 139-152 region and that this part of the protein is a native epitope. PMID- 1284324 TI - Role of autocrine and paracrine factors in thyroid follicle growth. AB - Basic fibroblast growth factor (bFGF), insulin like growth factor I and II and transforming growth factor beta (TGF-beta) are assumed to be of importance in the paracrine and autocrine regulation of thyroid growth and function. Using in vitro cultures of isolated intact porcine thyroid follicles, we here present data that support a possible autocrine action of bFGF on proliferation, a possible explanation for the observed potentiation of EGF-stimulated growth by IGF-I, and results on the release and regulation of release of TGF-beta. For growth experiments, thyroid follicles (2 x 10(5) cells) were incubated for 6 days followed by cell counting. For the analysis of EGF binding sites, follicles were preincubated with and without IGF-I (10 ng/mL) for 48 h at 37 degrees C, incubated with 125I-EGF (5 nCi/well) and unlabeled EGF (0.1-500 ng/mL) for 24 h at 4 degrees C (2 x 10(5) cells/well); binding characteristics were calculated from Scatchard analysis. The TGF-beta bioactivity in untreated and acid treated media conditioned with thyroid follicles for 3 days (2 x 10(7) cells) was analyzed with a bioassay using mink lung epithelial cells. Basic FGF (0.1-1 ng/mL) dose-dependently stimulated the proliferation of thyroid follicles up to 135.0 +/- 6.1%; this effect was additive with IGF-I (10 ng/mL) but not with EGF (2 ng/mL). The IGF-I (10 ng/mL) just moderately increased proliferation (128.3 +/ 16%), but potentiated EGF (1 ng/mL)-stimulated growth (from 183.0 +/- 11.0% to 314.0 +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284325 TI - Proceedings of the international symposium: goitrogenesis. Munich, December 5-6, 1991. Part 2. PMID- 1284326 TI - Effects of pineal-derived indolic compounds and of certain neuropeptides on the growth processes in the thyroid gland. AB - The aim of the present study was to examine the effects of melatonin (Mel) and of pinealectomy (PX) [in a long-term experiment in vivo - 10 weeks], as well as of Mel and N-acetylserotonin (NAc-5HT) [in experiments ex vivo in vitro and in vitro], on the rat thyroid growth processes. Additionally, the incubations in vitro of rat thyroid lobes with 3H-thymidine, in the presence of TSH, vasoactive intestinal polypeptide (VIP), VIP-antagonist ([4Cl-D-Ph6, Leu17]VIP), somatostatin (SS), all the substances used separately or jointly in combinations, were performed. It was shown that: (a) Mel--administered in late afternoon injections--decreased, while PX increased examined indices of thyroid growth in vivo, (b) Mel--administered in s.c. implanted pellets--reversed the inhibitory effect of Mel injections, (c) in experiments ex vivo in vitro and in vitro, the inhibitory effect of Mel revealed only for the lowest applied dose/concentration of the hormone, (d) NAc-5HT showed no effect, (e) VIP decreased 3H-thymidine incorporation into DNA of thyroid lobes in vitro and enhanced the inhibitory effect of SS on the process in question, (f) VIP-antagonist failed to reverse the inhibitory action of VIP on the thyroid growth. PMID- 1284327 TI - Selenium supply regulates thyroid function, thyroid hormone synthesis and metabolism by altering the expression of the selenoenzymes Type I 5'-deiodinase and glutathione peroxidase. AB - Selenium supply appears to be insufficient in several regions of Europe as indicated by analysis of plasma and tissue selenium content and measurements of selenium dependent glutathione peroxidases (GPx). Selenium deficiency alters both thyroid hormone synthesis and tissue specific activation by 5'deiodinase isoenzymes. Human and rat Type I 5'deiodinase have been identified as selenoprotein containing selenocysteine in its active site. Regulation of selenium dependent expression of Type I 5'deiodinase occurs at the transcriptional and posttranscriptional level and a cellular hierarchy of selenite incorporation was found for Type I 5'deiodinase over GPx in LLC-PK1 kidney cells. The role of other newly discovered selenoproteins for thyroid hormone synthesis, activation, and action has to be investigated. PMID- 1284328 TI - Iodine and goiter involution. AB - Iodine administration, although efficient in goiter treatment or prevention, is also responsible for adverse effects such as cell necrosis or thyroiditis. These two effects were reproduced in iodide-treated goitrous mice. Morphological observations strongly suggest that thyroid cell death results from an excessive production of free radicals, which initiates lipid peroxidation. This hypothesis is strengthened by the facts that the thyroidal concentration of malonic dialdehyde, a stable product of lipid peroxidation, is increased, and that necrosis is partially prevented by free radicals scavengers. Epithelial necrosis is associated to an inflammatory reaction. The infiltrate is mainly made of cells expressing class II molecules of major histocompatibility complex (macrophages and dendritic cells), but also of T lymphocytes. However, this inflammation, which varies among mouse strains, is transient and it is not amplified or maintained by administration of cytokines, IFN gamma or TNF alpha, known to induce class II expression on thyrocytes. PMID- 1284329 TI - Further studies on the antigoitrogenic action of iodoarachidonates. AB - Previous studies have shown that iodoarachidonates (IAs) prevent goiter production in rats. In the present studies we show that both IL-d and IL-w (IAs bearing the iodine atom at the positions 6 and 14, respectively), cause a significant involution of preformed goiter. This effect was evident when IAs were administered either orally or via i.p., although the first one required larger doses to obtain the same degree of inhibition. No changes were observed in serum protein, urea, cholesterol, cholinesterase, T3 or T4. In vitro studies with FRTL 5 cells showed that both IAs inhibit iodide and alpha-AIB uptake, as well as ATPase activity. PMID- 1284330 TI - The role of iodine and thyroid cell growth. AB - The autoregulatory effects of iodide on thyroid growth and function are discussed to be mediated by iodinated derivatives of essential fatty acids (EFA), esp. iodolactones. We now reevaluated the effect of iodide on proliferation of isolated porcine thyroid follicles by determination of cell counts and investigated the effects of pretreatment of the follicles with arachidonic acid (AA, C 20:4 n6) in comparison to docosahexaenoic acid (DHA, C22:6 n3). Growth experiments were performed in multi-well culture plates and cell counts were determined after 6 d of incubation. EGF (5 ng/ml) significantly stimulated thyroid cell proliferation (151 +/- 6%; Mean +/- SD vs. basal control, 100 +/- 8%). 2.5 microM of iodide, added 24 h before EGF, had a weak stimulatory effect (168 +/- 9%) whereas higher concentrations of iodide (5-80 microM) exerted significantly dose-dependent inhibitory effects (117 +/- 1% at 80 microM of KI) which could be abolished with 500 microM of methimazole (155 +/- 11% at 80 microM of KI). Isolated porcine follicles showed a rapid uptake of EFA (25 microM) measured by specific tracer activity in the ethanol/acetic acid extracts of follicles (1.60 +/- 0.48 mumol EFA/ml follicle/24 h). Treatment with DHA (100 and 300 microM) significantly enhanced the inhibitory effect of 10 microM of iodide on thyroid follicle proliferation (84 +/- 2% and 45 +/- 4%) in contrast to follicles pretreated with AA (100 +/- 8% and 60 +/- 8%). These results demonstrate the biphasic effect of iodide on thyroid growth which can be abolished by inhibition of iodide organification with methimazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284331 TI - Treatment of iodine deficiency goiter with iodine, levothyroxine or a combination of both. AB - During recent years several studies have been published comparing different ways of pharmacological treatment of a goiter due to iodine deficiency. These studies usually were performed with 300 to 500 micrograms of iodine, 100 to 150 micrograms levothyroxine, or a combination of in most cases 100 micrograms levothyroxine and 100 micrograms iodine. The largest data have been accumulated in 166 patients with in most cases diffuse goiter. Group A (n = 61) received 150 micrograms levothyroxine per day, group B (n = 50) 400 micrograms iodine per day and group C (n = 55) a combination of 75 micrograms levothyroxine and 200 micrograms iodine per day. During the eight months of therapy, in all three groups a significant and comparable mean decrease in goiter size was documented ( 32.1% in group A, -37.3% in group B and -38.7% in group C [n.s. between the three groups]). Striking differences between the three groups are evident in the changes of basal and thyrotropin releasing hormone (TRH) stimulated thyrotropin (TSH). In group A, after eight months a sharp and significant decrease of TSH occurred (from 1.2 mU/l to 0.4 mU/l; mean; p < 0.05), while in group B TSH showed only a minor decrease (from 1.3 mU/l to 0.9 mU/l) and remained significantly higher compared to both, group A and C (p < 0.01). Similar changes were documented when the TSH after TRH administration was calculated. It is concluded, that all three therapeutic approaches are effective for goiter reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284332 TI - Determinants of outcome in sporadic nontoxic goiter. AB - The author points out that natural history of sporadic nontoxic goiter (SNG) is characterized by increasing thyroid volume, nodularity and autonomy of function leading to hyperthyroidism in 13-16% of the patients after a medium follow-up of circa 12 years. Successively, the author reports and discusses the effectiveness and the outcome of the therapeutical modalities used for SNG: thyroidectomy, thyroid hormones and radioactive iodine. PMID- 1284333 TI - Interactions between the immune system and the thyroid. Regulatory networks in health and disease. AB - Hashimoto's thyroiditis, primary myxedema and Graves' disease are thyroid disease that are due to autoimmune reactions towards thyroidal antigens such as thyroid peroxidase (TPO), thyroglobulin (Tg) and the TSH receptor. Thyrocyte destruction in Hashimoto's thyroiditis and primary myxedema is caused by TPO- and Tg-specific lymphocytes and autoantibodies, thyrocyte stimulation in Graves' disease is caused by antibodies stimulating the TSH receptor, thyroid atrophy in primary myxedema is caused by antibodies blocking the TSH receptor, or a yet unknown thyroid growth receptor. The above listed thyroid autoimmune diseases are familial (genetically determined), and due to defects in the immunoregulatory mechanisms that should normally control excessive thyroid autoimmune reactivity. This control towards thyroidal antigens (tolerance) can be broken by professional antigen presenting cells, such as the dendritic cells. It is now known that thyroid autoimmune diseases are indeed initiated by dendritic cells: dendritic cells are present in low number in normal thyroids, but accumulate very early in thyroids that are later affected by thyroid autoimmune disease. Dendritic cells are also present in the normal anterior pituitary and in this gland they are known as the (folliculo) stellate cells, the regulators of growth and function of the surrounding pituitary-endocrine cells. It is discussed whether the influx and clustering of dendritic cells in the thyroid observed during early autoimmune thyroid disease is meant for the regulation of growth and function of the thyrocytes thus linking a putative early endocrine disturbance to the initiation of thyroid autoimmune disease. PMID- 1284334 TI - Use of FRTL-5 for the study of thyroid antibodies involved in goitrogenesis. AB - Some authors have suggested a role of autoimmunity in the pathogenesis of iodine deficiency disorders (IDD). For this purpose we have searched for thyroid adenylate cyclase stimulating antibody (TSAb) and thyroid growth stimulating antibody (TGSAb) in patients with endemic goiter (EG) and endemic cretinism (EC). Immunoglobulins G preparations (IgGs) were tested in FRTL-5 cells. TSAb were calculated as percent of cAMP increase over basal production and TGSAb were expressed as percent of increase of 3H-thymidine incorporation and DNA content in FRTL-5 cells. Our results show that IgGs from goitrous patients were devoid of TSAb and TGSAb activities, while in the same conditions IgGs from patients with Graves' disease had the ability to stimulate cAMP production and 3H-thymidine incorporation in FRTL-5 cells. These data argue against a direct role of TSAb and TGSAb in the pathogenesis of IDD. PMID- 1284335 TI - Involvement of the immune system in iodine deficient goiter. AB - Iodine deficient goiters were studied by immunohistochemistry and showed extensive presence and typical arrangement of dendritic cells, known to have excellent antigen presenting capacity. These cells were positive for all MHC class II epitopes and for ICAM-1. Epithelial follicle lining cells were also seen to be class II positive but lacked ICAM-1. Thyroglobulin seemed not to be iodinated at the C-terminal hormogenic site, as shown by reactions with monoclonal antibodies. Iodine therapy, as well as thyroxine therapy were effective in reducing thyroid size. Both forms of therapy were found to decrease the pretreatment levels of circulating thyroid growth stimulating immunoglobulins (TGI). PMID- 1284336 TI - Gi alpha-1 expression in the human thyroid is regulated by TSH: loss of regulation in thyroid autonomous adenoma. AB - The molecular mechanisms underlying the development of endocrine active thyroid tumors are poorly understood. These tumors produce excess thyroid hormone, which then suppresses TSH (thyroid stimulating hormone) production. In the present report, we show that the expression of Gi alpha-1 is under control of TSH in the normal human thyroid. In contrast Gi alpha-1 escapes TSH control in autonomous adenoma and thus is constitutively expressed. Since receptor-mediated activation of Gi controlled pathways is known to elicit a proliferative response in several cell types, we propose that in thyroid adenomas the unregulated constitutive expression of Gi alpha-1 is causally related to the autonomous growth. PMID- 1284337 TI - Simultaneous determination of 6-azacytidine, 6-azauridine, arabinoside cytosine and arabinoside uracil in blood by liquid chromatography. PMID- 1284338 TI - The hare parotid gland: ultrastructure and histochemistry of acinar and ductal cells. AB - The parotid gland of the hare Lepus europaeus was studied by electron microscopy. The parenchyma consists of secretory areas (acini) and ductal segments (intercalated, striated and excretory ducts). Acinar cells showed a marked heterogeneity due to the presence of secretory granules characterized by different size, electron-density and degree of membrane merging in addition to the occurrence of flattened and dilated rough endoplasmic reticulum. Acinar cells had variable affinity for PAS and PA-TCH-SP staining but were HID- and LIT-TCH-SP negative. Intercalated duct cells lacked secretory granules. Striated ducts were lined by four cell types namely light cells, dark cells, vacuolated cells, and typical striated cells. Excretory ducts showed some scalloping on the apical region of the light cells. PMID- 1284339 TI - Run charts. PMID- 1284341 TI - [Intracavitary urology and extracorporeal shock wave lithotripsy: a workshop discussion]. PMID- 1284340 TI - [Effects of combination chemotherapy of ovarian cancer in vitro]. AB - To investigate the effects of combination chemotherapy on ovarian cancer in vitro, we observed the sensitivity of tumors to different drugs by incorporation assay of tritium thymidine (3H-TdR). The results revealed that the drugs and their sensitive degrees varied from tumor to tumor. Whether the combination of the drugs is synergism or sometimes only enhances toxicity depends on the difference of individuals. We suggest that in vitro anti-cancer drug sensitivity test could be applied in selection or determination of chemotherapy protocol. PMID- 1284342 TI - Human immunodeficiency virus in gestational trophoblastic neoplasias--is it a poor prognostic risk factor. AB - Three cases of HIV infection with choriocarcinoma are presented. One case had prolonged chemotherapy without remission, the second had remission only after combining hysterectomy with chemotherapy and the third who had extensively metastatic disease in the presence of other low risk factors are reported. HIV infection may predispose patients to extensive metastatic choriocarcinoma and influence the course of treatment. We propose that HIV infection be considered a poor prognostic risk for gestation trophoblastic neoplasias. PMID- 1284343 TI - [The effect of substance P on histamine-stimulated gastric juice release and bile formation]. AB - The substance P was shown to be able to increase the level of histamine-induced stomach secretion and the debit of free hydrochloric acid in dogs. This peptide increases the volume velocity of the choleresis and the content of bile acids and protein in the bile. The substance P alters the range of the bile acids as well. PMID- 1284344 TI - [Comparative studies on LH/CG receptor from rat testes and hCG-binding protein from Pseudomonas maltophilia by antibodies against the hCG-binding protein]. AB - An indirect immunoprecipitation experiment was developed to characterize the antigenic determinants of the hCG-binding protein and the rat testicular LH/CG receptor. The hCG-binding protein preincubated with 125I iodo hCG was immunologically precipitated by the antibodies against the hCG-binding protein in the presence of goat anti-rabbit IgG. Similarly, the LH/CG receptor solubilized with 1% triton X-100 from the rat testes was also immunoprecipitated by the antibodies. Furthermore, the antibodies did not inhibit the binding of 125I iodo hCG to the hCG-binding protein or to the solubilized rat testicular LH/CG receptor. From these results it can be concluded that there exists the sharing of antigenic determinants between the hCG-binding protein from Pseudomonas maltophilia and the LH/CG receptor from the rat testes and that the antibodies specifically recognize the antigenic determinants outside the hCG-binding sites on the rat testicular LH/CG receptor. Therefore, the antibodies against the hCG binding protein are of potential applications to studies on structure and function of the mammalian LH/CG receptors. PMID- 1284345 TI - [A randomized control trial of isovolemic hemodilution therapy in cor pulmonale]. AB - The hemorheologic properties are obviously abnormal in patients with cor pulmonale (CP), presenting as high hematocrit (HCT), hyperviscosity and hyper viscoelasticity. Twenty patients suffering from CP with polycythemia were randomized into either an isovolemic hemodilution (IHD) group or control group. In the IHD group, 10 patients were treated by routine therapy combined with IHD. The other 10 patients in the control group were treated by routine therapy only. The results demonstrated that after treatment in IHD group, all viscoelasticity property parameters except eta p were decreased significantly. Oxygen delivery, oxygen transport capacity, and stroke volume and cardiac output were increased. Mean pulmonary artery pressure and total pulmonary resistance were decreased. However, in the control group only HCT and eta 0.512 were decreased after treatment. The viscosity and eta' of the whole blood in IHD group were decreased more markedly than those in the control group. IHD was well tolerated in most of the patients. There were no complications or side effects. Thus, IHD is a safe, effective and acceptable therapy, and it may play a role in the treatment of cor pulmonale. PMID- 1284346 TI - Utilization of the Boyden chamber to further characterize in vitro migration and invasion of benign and malignant human prostatic epithelial cells. AB - In the present study, we assessed various tissue culture conditions on the motility and invasiveness of benign and malignant prostatic epithelial cells using the Boyden chamber system. In DME and RPMI-1640 media, benign human prostatic epithelial cells were unable to penetrate through a basement-membrane coated filter. However, the prostatic carcinoma cell lines, PC3 and DU145, showed a significant frequency of invasion under those conditions. When cultured in the low-calcium WAJC 404 medium, benign prostatic epithelial cells efficiently penetrated through the basement-membrane-coated filter. PC3 and DU145 cells showed an attenuated capability to invade when cultured in WAJC 404 medium. The effect of extracellular calcium on the behavior of these cells in the Boyden chamber was further evaluated by gradual addition of calcium chloride in WAJC 404 medium. These studies showed that the number of benign prostatic epithelial cells penetrating through the filter decreased as the calcium ion concentration increased. Conversely, the number of PC3 cells invading through the filter increased as calcium ion concentration was increased to 0.4 mM and decreased at higher calcium ion concentrations. These results suggest that the extracellular calcium concentration is one of the factors which may affect cell behavior in the Boyden chamber system. PMID- 1284347 TI - Effect of injury on pulpal levels of immunoreactive substance P and immunoreactive calcitonin gene-related peptide. AB - Neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P are present in dental pulp in relatively high concentrations. Previous studies have demonstrated that the staining density of immunoreactive CGRP (iCGRP) changes in dental pulp after tissue injury. This study evaluated injury-related changes in levels of both immunoreactive CGRP (iCGRP) and immunoreactive substance P (iSP) in dental pulp using radioimmunoassays. After pulpal exposure, iSP levels decreased to about 10% of baseline values, while iCGRP levels decreased to about 45% of baseline measures. After dentin exposure with acid etch, iSP levels decreased to about 10 to 20% of baseline measures, while iCGRP levels decreased to 60% of baseline values. For both forms of injury, iSP decreased to a greater extent than did iCGRP levels. Collectively, these findings indicate that pulpal neuropeptides undergo dynamic, injury-specific, and peptide-specific responses following trauma to dental pulp. PMID- 1284349 TI - [Narcotic analgesics. Part III. Total and partial agonists of opiate receptors]. PMID- 1284348 TI - An in vitro method to evaluate regulation of neuropeptide release from dental pulp. AB - Although pulpal neuropeptides such as calcitonin gene-related peptide and substance P may mediate neurogenic inflammation, little is known about the regulation of neuropeptide release from dental pulp. This article describes an in vitro method for superfusing dental pulp which permits the study of mechanisms regulating the release of immunoreactive CGRP (iCGRP). Tissue extracts from bovine dental pulp dilute in parallel to authentic calcitonin gene-related peptide and substance P peptide standards when assayed by radioimmunoassay. Pulpal levels of iCGRP were 17-fold greater than levels of immunoreactive substance P. Administration of a potassium pulse evoked a significant release of iCGRP from dental pulp (155 +/- 21 fmol/g/9 min) as compared with iCGRP spontaneously released from concurrent control chambers (18 +/- 11 fmol/g/9 min). The in vitro superfusion of pulp tissue may serve as a useful method for identifying peripherally acting drugs which modulate nociceptor secretory activity and for determining their mechanisms of action. PMID- 1284351 TI - [Development of a system for cloning a DNA fragment, containing the determinant of resistance to actinomycin for Streptomyces chrysomallus No.2--a producer of actinomycin C]. AB - To study the modes of actinomycin biosynthesis and the mechanism responsible for resistance to the antibiotic producing S. chrysomallus No. 2, the authors undertook an examination and studies into the cloning system for gene(s) of resistance to actinomycin from a S. chrysomallus No. 2 actinomycin C producer and the cloning of a S. chrysomallus No. DNA fragment to the actinomycin-sensitive Streptomyces Sp. 26-115 H-I on the vector plasmid pIJ702. The cloning gave rise to actinomycin-resistant strains. The character of actinomycin resistance is inheritable in a steady fashion. PMID- 1284350 TI - [The extracellular ionic environment and bone metabolism. In vitro study of the role of chloride]. AB - Controversies surround the view that the blood-bone ionic equilibrium is controlled by ionic changes at a so called "bone membrane" that display a pump leak mechanism able to maintain a concentration gradient for chloride in addition to that for calcium, sodium and potassium. On the other hand it is known that a chloride-bicarbonate transport is active at bone cells membrane to control cytosolic pH. We tested the hypothesis that a modification of the chloride concentration of the culture medium, as well as a block of the chloride bicarbonate transport by an anionic channels blocker, in an experimental model that keeps intact the bone membrane, may influence the bone cells activity and that the influence may be quantitatively different to that previously observed in isolated bone cells. The experimental model is the intact fetal rat limb bone, cultured for 24 hours in a simplified medium at different chloride concentrations obtained by substituting chloride with isethionate. Alkaline phosphatase activity released in the medium was measured as a marker of osteoblasts activity. By progressively reducing the chloride concentration from 117 mM to 29 mM, alkaline phosphatase activity was found unchanged. By dramatically reducing the medium chloride concentration to the range 14-0 mM, alkaline phosphatase activity was significantly (p = 0.0002) inhibited by 31.58%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284352 TI - [Properties of intracellular virus-specific ribonucleoproteins containing negative and positive hepatitis A virus RNA]. AB - The characteristics of the intracellular virus-specific nucleocapsids containing either a negative or a positive RNA strand were studied. The immunosorption of nucleocapsids by the monoclonal antibodies against the three epitopes of NP protein failed to reveal any antigenic difference between the negative strand or positive strand-containing nucleocapsids. On the other hand, the sensitivity of virus-specific RNA in the nucleocapsids to digestion by the pancreatic ribonuclease proved to be lower for the positive strand-containing nucleocapsids. PMID- 1284353 TI - The final week. PMID- 1284354 TI - Appointed to the post. PMID- 1284356 TI - Automatic measurement of hemoglobin F in blood obtained from patients with hemoglobin E/E and beta-thalassemia/hemoglobin/E. AB - This paper presents an automated determination of hemoglobin (Hb) F in Hb E/E disease using Hi-Auto A1c. Blood specimens collected in Bangkok were frozen, and sent to Japan by air mail for the determination. The automatically determined values showed a high correlation with the values obtained by the classical alkali denaturation method. Hb E/E cases showed 4.24 +/- 1.75% of Hb F. On the other hand, Hb, Hct, MCV and MCH in the disease samples were lower than in the controls, but higher than those of beta-thalassemia/HbE disease. From the results it was concluded that Hb E/E could be differentiated from beta-thalassemia/HbE by combination of Hb F value and MCH or Hb in CBC. PMID- 1284355 TI - [Changed levels of substance P and somatostatin in HIV-positive children]. AB - Substance P (sP) and Somatostatin (SOM), so as other neuropeptides can modulate neurologic and immunologic functions. sP has been described to enhance both in vitro and in vivo immunoglobulin synthesis. On the contrary, SOM has an inhibitory effect on the same activity. The modulating effect is more evident on IgA isotype. Hypergammaglobulinemia and in particular high levels of IgA is a common finding in pediatric AIDS and an imbalance among regulatory effects of neuropeptides might be suggested. In order to evaluate the plasma levels of sP in pediatric AIDS we studied 15 children with HIV infection (status P2), 10 seronegative children born to HIV positive mothers and 10 healthy children of the same age. All the HIV positive children had high plasma levels of IgG and IgA. The plasma level of sP was extremely higher in HIV positive children while no significant difference was found between seronegative children born to HIV positive mothers and healthy children. SOM was decreased in HIV positive children when compared to control groups but a significant difference was not reached. It might be supposed that HIV infection, through a dysregulation among neuropeptides interferes on immune functions and in particular on IgA synthesis. On the other hand it might be suggested that the imbalance between sP and SOM depends on the viral infection of immune cells since it has been demonstrated that SOM and other neuropeptide are synthesized by lymphoid tissue. Further studied relevance of neuropeptide disorders in pediatric AIDS. PMID- 1284357 TI - Red blood cell and platelet induced differentiation of endothelial cells into capillary-like structure. AB - We cultivated endothelial cells of human umbilical vein origin in the presence of red blood cells and platelet-rich plasma, and observed the phenomena which occurred in the petri dish under phase contrast microscopy. Many small particles were observed after an overnight incubation. We washed the dish two times, then added thrombin to the dish. The network of thread-like strands appeared within 10 to 20 minutes of the addition, and at the same time the small particles adhered on the surface of the strands, swelled and fused gradually to cover the surface of the strands completely. Within 30 to 60 minutes the network of the strands changed into a capillary-like structure. These phenomena were not observed if we omitted red blood cells or platelet-rich plasma. Studies by transmission electron microscopy revealed that the inner surface of the lumen of the structure was covered with cells. The cells isolated from the lumen by trypsin grew to confluence in the conventional culture medium, and showed vWF antigen on their surface. These observations indicated that the method described is useful for in vitro study of angiogenesis. PMID- 1284358 TI - Reconstruction of neural networks is organized by co-existence of various signal molecules or input activation in Helix pomatia L. AB - The overlapping neural networks consisting of multifunctional neurons were shown to take part alternatively in regulation of various visceral functions or behaviour. The reconstruction of the neural networks was shown to be a function of input activation or transmitter cocktail used at the vicinity of the neurons. In rearrangement of neural networks acetylcholine (Ach), serotonin (5HT) and molluscan neuropeptide, FMRFamide were found to be effective. The modulation occurs at the level of ion channels and at least three different types, namely the Ca-, delayed K- and the unspecific cation channels were shown to be responsible for it. The modulatory action of low molecular weight neurotransmitters and peptides was more often directed to the same species of ion channels, but the maximum of channel activation can appear at different voltage ranges. The modulation of afferent and efferent pathways by signal molecules can assure the mosaic-like functioning of the units of neural networks. PMID- 1284359 TI - Somatotopic representation of the head areas in the cerebral ganglion of the snail Helix pomatia. AB - This study gives a detailed description of the central representation of the head regions in the cerebral ganglion after parallel nickel-lysine and cobaltic-lysine backfilling of different pairs of cerebral nerves. The backfilling of the cerebral nerves demonstrate different groups of labelled neurons in the cerebral ganglion as in the procerebrum, mesocerebrum, metacerebrum, as well as in the pleural, pedal and commissural lobes of the postcerebrum. Each head area except the anterior and posterior tentacle is represented in each labelled cell group. The tentacles are not represented in the mesocerebrum and the pedal lobe of the post-cerebrum. The different head areas in the procerebrum, metacerebrum and the pleural lobe are represented in fronto-caudal a somatotopic order. PMID- 1284360 TI - Immunohistochemical and ultrastructural study of the enteric nervous system of earthworm, Lumbricus terrestris L. AB - Light and electronmicroscopic data reveal the presence of a well developed nerve plexus in the gut of the earthworm. The plexus contains subepithelial solitary nerve cells and fibers and an extensive neuropil among the muscle cells. There are two types of nerve cells in the enteric plexus. The first type contains mainly dense-core vesicles, and exhibits glyoxylic-acid induced fluorescence. Since none of these cells showed serotonin immunoreactivity, they are probably noradrenergic or dopaminergic. The second type contains large dense granules, suggesting that these cells are peptidergic (neurosecretory). A part of these cells are substance P immunoreactive, however no NPY, CGRP, or proctolin immunopositive cells were found. Ultrastructurally seven types of nerve fibers can be distinguished in the neuropil. Their distribution shows great variability within parts of the enteric canal. The observation that only two types of nerve cells are located within the gut makes it probable that some of the axons are extrinsic. According to immunohistological studies they may come from the stomatogastric system or from the segmental nerves. This is further supported by the fact that there is a well-developed subepithelial serotoninergic plexus in the fore-gut. Two types of neuromuscular junctions can be visualized in the muscular layer. The first type, representing a phylogenetically earlier form, exhibits wide junctional gap and pre- or postjunctional membrane thickening. The second type is the close contact. There are significantly more junctions observed in the fore-gut than in other parts of the gut. PMID- 1284361 TI - Activation of a divalent cation-conducting channel in heart ventricle muscle cells of the snail Lymnaea stagnalis by the molluscan cardioactive peptide FMRFamide. AB - Ion channels with characteristics of Ca2+ channels have been found in isolated heart ventricle cells of the snail Lymnaea stagnalis. Although spontaneous Ca2+ or Ba2+ currents were seen only occasionally, spontaneous inward Na+ currents were readily observed in the absence of patch pipette Ca2+ between membrane potentials of -100 mV and +20 mV. These currents were blocked by 2 mM Ni2+, 2 mM Co2+ and 10 microM Ca2+. The channels usually ceased conducting within a few minutes after seal formation with the patch pipette and could not be re-activated with depolarizing voltage steps. However, at the cell's resting potential, 10(-8) to 10(-6) M of the molluscan cardioactive peptide FMRFamide or its analogue FLRFamide2+ applied to the cell membrane away from the patch pipette, induced unitary Ba2+ currents or, in the absence of Ca2+ in the patch pipette, Na+ currents. This suggests that a secondary messenger is involved in the FMRFamide induced activation of these channels rather than a direct activation of a channel receptor complex by the peptide. PMID- 1284362 TI - Vital staining with 5(6)-carboxyfluorescein in the feeding system of Lymnaea and the selective photoinactivation of the filled neurones. AB - Lymnaea feeding interneurones were stained with 5(6)-carboxyfluorescein by cutting the nerves containing their axons. They were located under low-intensity blue light and were healthy with normal pharmacology. The interneurones were selectively killed by high-intensity blue light. PMID- 1284363 TI - Calcium transients in snail neurones. PMID- 1284364 TI - [Palliative treatment with an endoluminal prosthesis for obstruction of the esophagus and the cardia]. AB - Between December 1984 and September 1991, a total of 68 palliative esophageal intubations were performed in 57 patients. The mean age was 64 years, there were 40 males and 17 females. The more frequent causes of esophageal obstruction were malignant tumors of the esophagus (49%), lung (23%) and cardia (19%). Total dysphagia (24.5%), dysphagia to liquids (47%) and esophagotracheal aspiration (14%) were present in these patients. In 65% of patients insertion of the prosthesis was the first attempt at palliation, in the remaining patients it followed the failure of another type of palliation. The decision to palliate esophageal obstruction was established preoperatively in 86% of patients, in the remaining 14% it was decided at the time of surgery. The intubation by pulsion (Atkinson) [1] was successful in 57% of patients and by traction (Celestin) [2] in 86% of patients. The associated morbidity was 36% for the Atkinson prosthesis and 13% for the Celestin prosthesis, although the latter required a laparotomy. The in hospital mortality was 12.5%. The mean survival was 85 days. A normal or semi-solid diet was tolerated by over 60% of patients following intubation. Palliation of esophageal obstruction by intubation improves the quality of life but is associated with a high morbidity. PMID- 1284365 TI - The effect of isoprinosine treatment on histamine release from murine peritoneal mast cells. AB - The study was undertaken to examine the effect of isoprinosine treatment on in vitro histamine release from peritoneal mast cells. The experiments were done on mice which received isoprinosine orally, at a dose of 50 or 100 mg per kilogram of body weight per day, in divided doses, every 8 hours, for a period of 1-9 days. After isoprinosine treatment, there was a significant decrease of in vitro Con A-induced histamine release from mast cells. This inhibitory effect was observed in both tested groups. In the second experiment, with mice sensitized with egg albumin, the treatment with isoprinosine gave also a significant inhibition of anaphylactic histamine release from mast cells, as compared with that of control without isoprinosine treatment. Results of both experiments suggested that isoprinosine may have some inhibitory effect on mast cell activation. PMID- 1284366 TI - Seleno-organic compounds induce interferon and tumor necrosis factor in human but not in rat or mouse lymphoid cells. AB - The seleno-organic compounds are highly active in several anti-inflammatory assays performed in mice and rats. However, they differ from the classical non steroidal anti-inflammatory drugs including indomethacin despite the fact that both types of drugs are inhibitors of prostaglandins and leukotrienes. Furthermore, ebselen and analogs are potent anti-oxidants in many animal cell cultures. The toxicity of the drugs is low because selenium in their structure is not bioavailable. We have discovered that the seleno-organic compounds induce interferon gamma (IFN-gamma), IFN-alpha, tumor necrosis factor alpha (TNF-alpha) and other cytokines in human peripheral blood leukocytes (PBL). Furthermore, the action of the drugs and PHA or Con A was synergistic. However, ebselen and analogs were found to be inactive as the cytokine inducers in cultured rat or mouse lymphoid cells. In contrast to their effects in human PBL, the drugs even inhibited the production of IFN-gamma after stimulation with PHA or Con A. The inhibition was dose dependent. We suggest that the induction of IFN by ebselen and analogs is species specific and it may depend on interaction of the drugs with a specific receptor and/or signal-transducing system present in human but not in some animal cells. PMID- 1284367 TI - Histamine secretion from human mesenteric and adenoidal mast cells. AB - Human mast cells were obtained from adenoids and mesentery by enzymatic dispersion of the tissues with the enzyme collagenase. The digestion of the tissues resulted in a cell suspension which contained 1-2% mast cells. 37.3% (adenoids) and 33.4% (mesentery) of total histamine initially present in the tissues was recovered in the dispersed cell suspensions. More than 90% of the cells were viable. The adenoidal mast cells could be sensitized passively in vitro with homologous reaginic serum and released histamine after challenge with specific antigen. Both populations of mast cells were sensitive to the action of anti-human IgE; the reversed anaphylaxis with anti-IgE was higher in mesenteric mast cells. Both examined mast cell populations were sensitive to the challenge with polymyxin B, concanavalin A and ionophore A23187, however, histamine release was only up to 10% and 20% for adenoidal and mesenteric cells, respectively. Only mesenteric mast cells responded to the action of compound 48/80. Histamine release, induced by polymyxin B, was rapid (maximal release within 5 min), maximal in the presence of 3 mM extracellular calcium ions (but also occurred in the absence of the cation). PMID- 1284368 TI - Failure of myocardial inactivation: a clinical assessment in the hypertrophied heart. AB - BACKGROUND: Abnormal intracellular calcium handling is observed in hypertrophied cardiac muscle and in end-stage heart failure muscle. This abnormal calcium handling results in prolongation of the calcium transient and in a biphasic calcium transient with prominent late component. In the present studies, the mechanical correlates of abnormal calcium handling were investigated in the hypertrophied human left ventricle by analysis of: 1) isovolumic left-ventricular relaxation kinetics after drastic left-ventricular unloading in patients with severe aortic stenosis after sequential balloon aortic valvuloplasty-arterial vasodilation; and 2) morphology of the diastolic left-ventricular pressure signal in patients with aortic stenosis and hypertrophic cardiomyopathy. METHODS AND RESULTS: Drastic left-ventricular unloading in patients with severe aortic stenosis by sequential aortic valvuloplasty-arterial vasodilation resulted in a slow and dyssynchronous left-ventricular relaxation pattern, as evident from a prolongation of the time constant of left-ventricular pressure decay from 46.6 +/ 12.5 to 73.2 +/- 23.3 ms (p < 0.01), and from the development of a convex downward negative dP/dt upstroke pattern. Abnormal diastolic left-ventricular pressure wave forms consisting of continuous left-ventricular pressure decay throughout diastole and/or a secondary pressure rise in mid-diastole were observed in patients with aortic stenosis and with hypertrophic cardiomyopathy. Postextrasystolic potentiation caused further slowing of this abnormal diastolic left-ventricular pressure decay, as evident from the decrease in phase of the first harmonic of a Fourier transform applied to the diastolic left-ventricular pressure wave. When an abnormal diastolic left-ventricular pressure wave form was observed at rest or after postextrasystolic potentiation, a simultaneously recorded left-ventricular monophasic action potential signal revealed the occurrence of delayed afterdepolarizations. CONCLUSIONS: The mechanical correlates of abnormal calcium handling or of inactivation failure in the hypertrophied human left ventricle consist of slow and dyssynchronous left ventricular isovolumic relaxation after left-ventricular unloading and of diastolic left-ventricular aftercontractions, which hinder left-ventricular filling and which are accompanied by delayed afterdepolarizations. PMID- 1284369 TI - Growth factors, growth factor response elements, and the cardiac phenotype. AB - Fibroblast growth factors (FGF) and type beta-1 transforming growth factor (TGF beta 1) are pleiotropic regulatory peptides which are expressed in myocardium in a precise developmental and spatial program and are up-regulated, in the adult heart, by ischemia or a hemodynamic burden. The accumulation of trophic factors after aortic banding supports the hypothesis that autocrine or paracrine pathways might function to mediate, in part, the consequences of mechanical load. Our laboratory has demonstrated that cardiac muscle cells are targets for the action of peptide growth factors and, more specifically, that modulation of the cardiac phenotype by basic FGF (bFGF) and TGF beta 1 strongly resembles the induction of fetal cardiac genes--including skeletal alpha-actin (SkA), beta-myosin heavy chain, and atrial natriuretic factor--which are characteristic of pressure overload hypertrophy. Unexpectedly, and despite effects like those of bFGF on five other cardiac genes, acidic FGF (aFGF) was found to repress, rather than stimulate, SkA transcription in neonatal cardiac muscle cells. The proximal 200 nucleotides of a heterologous SkA promoter were sufficient for basal tissue specific transcription, for induction by bFGF, and for inhibition by aFGF. Thus, both positive and negative regulation by peptide growth factors can be localized to the proximal SkA promoter. Full promoter activity required each of three CC[A/T]6GG motifs similar to the serum response element (SRE) for activation of the c-fos proto-oncogene, as previously shown for SkA transcription in a skeletal muscle background. The most proximal SRE, SRE1, was sufficient in the absence of other SkA promoter sequences for efficient tissue-specific expression in cardiac myocytes (versus cardiac fibroblasts), and was stimulated by bFGF to the same extent as the full-length promoter and endogenous gene. Despite its ability to repress the SkA promoter, aFGF had no significant effect on SRE1. Both FGFs up regulated the canonical fos SRE, to a comparable degree. Thus, SRE1 can discriminate between signals generated in cardiac myocytes by bFGF and aFGF. In cardiac myocyte extracts, two predominant proteins contact SRE1: serum response factor (SRF) and a second protein, F-ACT-1. Thus, serum response factor and F-ACT 1 are candidate trans-acting factors for basal transcription of the SkA gene in cardiac muscle cells and for induction of SkA by bFGF and, potentially, other trophic signals. PMID- 1284370 TI - Molecular structure and mechanisms of action of cyclic and linear ion transport antibiotics. AB - As a direct result of the vision, determination, and magnetic personality of Yuri Ovchinnikov a collaboration between the Shemyakin Institute of Bioorganic Chemistry and the Medical Foundation of Buffalo was begun in the early 1970's. The collaboration generated valuable insight into the structural basis for the capture, transport, and release of ions by ion transport antibiotics and the basis for the ion selectivity of these compounds. The collaboration produced dozens of joint publications on the structure and function of cyclic and linear ion transport antibiotics, fostered fruitful exchange visits between scientists in the two Research Institutes and has been a major source of creativity in my scientific career and those of many of my colleagues in Buffalo. This review summarizes major accomplishments of the collaboration. PMID- 1284371 TI - Thyroid neoplasms. Can we do any better with quantitative cytology? AB - The differential diagnosis of thyroid neoplasms by routine cytology presents major difficulties. We therefore looked for measurable nuclear parameters that could be generated from Feulgen-stained smears obtained by fine needle aspiration biopsy (FNAB). These parameters would then be used to differentiate between benign and malignant lesions. Seventy-six patients whose cold thyroid nodule was surgically excised after FNAB and examined by a pathologist were used in this study: 56 benign, 18 malignant and 2 atypical adenomas. A set of 3,662 cells from the 33 benign cases was compared with the set of 1,712 cells from the 11 malignant nodules. Discrimination between the two populations was based on four nuclear features ranked according to their discriminating power. The first ranked was a textural parameter, followed by a densitometric and finally two other textural parameters. The rate of nuclei that could be regarded as benign was computed for each case using the ranked parameters. The average rate for the 33 benign cases was 85% (50.2 = 100%, set at the 95% confidence interval). In a prospective study of the 32 remaining patients, sensitivity and specificity were, respectively, 92% and 88%, which were higher than those obtained by conventional cytology. PMID- 1284372 TI - Computer-aided S-phase fraction determination in DNA static cytometry in breast cancer. A preliminary methodologic study on cytologic material. AB - This methodologic study was performed on a single-cell-cycle breast carcinoma to evaluate the feasibility of computer-aided S-phase fraction determination in DNA static cytometry. The investigation was performed on Feulgen-stained cytologic material in which the total optical density values of 1,000 consecutive, randomly selected nuclei were analyzed (MultiCycle software). A good correlation in the S phase fraction value with flow cytometry was obtained when the G2/G1 ratio was fixed at 1.95, when the histogram data points were smoothed at least once and the coefficient of variation of the G2 peak was the same as that of G0-G1 or when a first-order S-phase polynomial model was used. The percentages of nuclei in G0-G1 and G2 were somewhat similar to those obtained with flow cytometry. The greatest discrepancy with flow cytometry was observed in the value of the coefficient of variation of the G0-G1 peak of the static cytometric data: it was at least twice as great. It always remained high despite the software options used. As for the influence of the sample size in the S-phase calculation, the software was also run on samples of 600 and 200 nuclei. When the G2/G1 ratio was fixed at 1.95, the data obtained from 600 nuclei did not differ from those obtained with 1,000 nuclei, whereas an analysis on 200 nuclei showed a substantial variation. The software also allowed calculation of the ratio of the G0-G1 peak of the neoplastic population against that of the diploid reference (DNA index), the value of which in flow cytometry was 1.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284373 TI - New techniques for three-dimensional data analysis in histopathology. AB - This paper describes two three-dimensional (3D) analytical techniques based on 3D mathematical morphology that have been found useful in quantifying the 3D spatial distribution of S-phase cells in a tubular tumor of the human breast. One technique is based on determining the normalized radial distribution of the S phase cells with respect to the central axis of the tumor. The other technique is a novel extension of the polyhedra of Voronoi to quantify the distribution. The Voronoi polyhedron of a given S-phase cell nucleus is that polyhedron of minimal volume defined by planes all of which are perpendicular bisectors of the vectors extending from the given cell to all other S-phase cells in the tumor. Methods are demonstrated for generating these polyhedra and for histogramming their volumes. An illustration is given of using the histogram to sort the S-phase cells according to their 3D positional relationships. Displays showing the sorted cells in 3D and their associated Voronoi polyhedra are provided. PMID- 1284374 TI - Prevalence of hepatitis C virus antibody among Korean adults. AB - To estimate the prevalence of hepatitis C virus (HCV) infection among Korean adults and to present the putative route of HCV transmission among them, serum samples from 4917 adults older than 20 years of age were tested for antibody to HCV (anti-HCV), and histories of blood transfusion and other pertinent information were obtained by self-administered questionnaires. The overall prevalence of anti-HCV was 1.7%; prevalence was 1.4% in subjects with normal levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), 3.3% in those with slightly elevated and 5.9% in those with markedly elevated levels of the enzymes. The prevalence of anti-HCV increased with increasing age (P < 0.01), but was not associated with blood transfusion. The present study suggests that the prevalence of HCV infection was 1.4% and that the major routes of HCV transmission may be other than blood transfusion in healthy Korean adults. PMID- 1284375 TI - [Substance P in human vocal cords]. PMID- 1284376 TI - [A case of hepatocarcinoma preceded by several years by "isolated" increase in alphafetoprotein]. AB - Hepatocarcinoma (HCC), the most frequent malignant hepatic neoplasia, is sometimes difficult to diagnose at an early stage since the symptoms may be attributed to concomitant hepatic cirrhosis. The assay of alpha-fetoprotein associated with an ultrasound examination of the hepatic parenchyma is an important screening tool for high-risk patients. Ultrasound examination is considered the most sensitive method and alpha-fetoprotein is a supplementary diagnostic tool. Elevated alpha-fetoprotein only occasionally precedes morphological anomalies and even in these cases the neoplastic aspect emerges within a short period of time. The case reported here illustrates the "astronomic" increase of alpha-fetoprotein in a high-risk patient for HCC (positive HBsAg cirrhosis) without the manifest appearance of any instrumental or histological data confirming the presence of the tumour for two years. When the tumour was identified in instrumental tests it had spread throughout the entire hepatic parenchyma in a form which could no longer be treated using any form of therapy. The case reported here emphasizes the diagnostic value of alphafetoprotein in high-risk patients for HCC, even in the prolonged absence of all other data regarding neoplastic transformation. PMID- 1284377 TI - Production and characterisation of a human monoclonal thyroid peroxidase autoantibody. AB - A human-mouse hybridoma has been produced by fusion of Hashimoto thyroid lymphocytes with the mouse myeloma line X63-Ag8.653. The cloned hybridoma secreted 2.5 micrograms per 10(6) cells per day of an IgG kappa thyroid peroxidase (TPO) autoantibody (2G4) with high affinity (2.5 x 10(9) molar-1) and specificity for human TPO. 2G4 did not react with lactoperoxidase, horseradish peroxidase or human myeloperoxidase or with porcine TPO or with human thyroglobulin. Plastic tubes coated with 2G4 bound about 50% of 125I-labelled human TPO added and the binding was inhibited by IgGs prepared from 18/18 TPO autoantibody-positive sera. This indicated that all 18 sera contained autoantibodies which recognised the same (or closely related) epitope as 2G4. Plastic tubes coated with IgGs from different TPO autoantibody-positive patient sera also bound 125I-labelled TPO but inhibition by 2G4 in this system was not complete. This suggested that the sera contained at least 2 types of TPO autoantibodies, with only one type of autoantibody reactive with the same epitope as 2G4. PMID- 1284378 TI - Lymphocytes utilise sialylated surface molecules to accumulate in developing lesions of autoimmune encephalomyelitis. AB - The accumulation of desialylated radiolabelled normal spleen cells and non neuroantigen specific CD4 T-lymphocytes was measured in the lumbosacral spinal cord of Lewis rats with autoimmune encephalomyelitis (EAE) induced with myelin basic protein in Freund's adjuvant. The labelled cells were preincubated with sialidase and thoroughly washed prior to intravenous injection into rats exhibiting early clinical signs of EAE. Four hours later, the rats were killed and blood and spinal cord samples were radioassayed. Compared with untreated cells, desialylation markedly reduced the accumulation of both normal spleen cells and memory T-lymphocytes in the spinal cord, despite similar levels of cells being present in the blood. In another experiment, the accumulation of desialylated, macrophage-depleted spleen lymphocytes was measured during the onset, recovery and short-term "relapse" phases of acute EAE. Again, compared with controls the accumulation of desialylated lymphocytes was always significantly less, despite similar numbers of cells in the circulation. Lastly, intravenous injections of sialidase produced delayed onset of both clinical and histological signs in rats with passively-transferred EAE. These data confirm and extend previous findings, using a different animal model, that sialyl residues on the lymphocyte surface are important to the accumulation of such cells at inflammatory sites in the central nervous system. The possible relevance of these findings to human demyelinating disease is discussed. PMID- 1284380 TI - The role of intermediate filaments in early Xenopus development studied by antisense depletion of maternal mRNA. AB - The effects of depleting a maternal cytokeratin mRNA on the developing embryo are described. Cytokeratins are members of the intermediate filament family of cytoskeletal proteins, and are expressed in a cortical network of the superficial cytoplasm of the oocyte. After fertilisation, a new cortical network is built up, which comes to occupy only the most superficial cells of the blastula. The maternal cytokeratin mRNA is abundantly translated, both during oogenesis, and during oocyte maturation and after fertilisation. Depletion of the mRNA results in depletion of the cortical filaments at the blastula stage and leads to gastrulation abnormalities. We discuss the various possible control experiments required for antisense oligo depletion studies and the implications of these results for cytokeratin function. PMID- 1284379 TI - Autoantibodies to the Ro/SSA antigen are conformation dependent. I: Anti-60 kD antibodies are mainly directed to the native protein; anti-52 kD antibodies are mainly directed to the denatured protein. AB - Recent studies have shown that Ro/SSA autoantigen is heterogeneous and the autoanti-Ro/SSA response is correspondingly heterogeneous. There are two isoform families; the 60 kD forms and the 52 kD forms. We studied the antigenic difference between the native and denatured Ro/SSA isoforms and found that the autoanti-Ro/SSA response to the native 60 kD antigen is quite homogeneous. All anti-Ro/SSA sera recognize the native kD antigen regardless of the reactivities to the 60 kD band on the Western blot. Surprisingly, no anti-Ro/SSA sera without anti-La/SSB reacts with the native 52 kD Ro/SSA, although sera with both precipitating anti-Ro/SSA and anti-La/SSB can immunoprecipitate the native 52 kD antigen. Anti-Ro/SSA sera exist which react exclusively with the native 60 kD Ro/SSA protein (10/43, 23%) while no anti-Ro/SSA sera have been found which react exclusively with the denatured 52 kD Ro/SSA antigen. In sera with anti-Ro/SSA precipitins alone, only antibody to the denatured 52 kD Ro/SSA molecule is found! In sera with anti-Ro/SSA and anti-U1 RNP precipitins, no antibody to either native or denatured 52 kD Ro/SSA is found, while in sera with both anti-Ro/SSA and anti-La/SSB precipitins, antibodies to both the native and denatured forms of 52 kD Ro/SSA are present. These data suggest that the anti-Ro/SSA response to the 60 kD molecule is driven by the native 60 kD Ro/SSA molecule while the molecular identification of the antigen drive in the anti-52 kD Ro/SSA response is unknown. PMID- 1284381 TI - Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer associated antigens in human colon cancer cells. AB - Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19 9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells. PMID- 1284383 TI - National Advisory Committee on Immunization (NACI). Statement on influenza vaccination for the 1992-93 season. PMID- 1284384 TI - Cholera in the Americas. PMID- 1284382 TI - Measurement of uptake and incorporation of nucleic acid precursors by preimplantation mouse embryos after development in vivo and in vitro. AB - PURPOSE: To assay DNA and RNA synthesis by developing mouse embryos in vitro and in vivo, we measured the uptake and incorporation of 3H-thymidine and 3H-uridine by morulae and blastocysts. We also evaluated the effect of adding EDTA to the culture medium on the uptake and incorporation of nucleic acid precursors by blastocysts. RESULTS: Thymidine and uridine incorporation increased after morulae developed into early blastocysts both in vitro and in vivo. However, the rates of uptake and incorporation were significantly lower by embryos grown in vitro than by those grown in vivo. The ratios of incorporation to total uptake were similar in embryos grown in vitro and in vivo. EDTA (100 microM) added to the culture medium significantly increased the incorporation of uridine into RNA by blastocysts grown in vitro (P < 0.01) but did not increase the total uptake of uridine. CONCLUSION: These observations showed that both DNA and RNA synthesis increased during the early development of preimplantation embryos and that those activities were reduced in embryos undergoing development in vitro. The results also suggested that through the mechanism of EDTA effect in embryo culture remains unknown, it appeared to reduce the retardation of RNA synthesis by embryos cultured in vitro through a selective stimulation of uridine incorporation. PMID- 1284385 TI - [The diagnostic value of erythrocyte polyamines (EPA) in prostatic adenocarcinoma (PA): apropos of 100 patients]. AB - Spermidine and spermine are ubiquitous polyamines which are intensely metabolised in the prostate. Polyamines are involved in the processes of proliferation and differentiation of normal and neoplastic cells. As the erythrocyte levels of these polyamines are correlated with the intratumoral levels, we assayed EPA in 45 controls, 66 patients with benign prostatic hypertrophy and 100 patients with prostatic cancer. Erythrocytic polyamines are markers of proliferation and prostatic metastases and can be used to distinguish between hormone-sensitive and hormone-resistant patients. Although non-specific, polyamines constitute circulating markers of the state of tumour proliferation of a given patient and definitely have a prognostic value which needs to be evaluated by further studies. PMID- 1284386 TI - [Progression after radical prostatectomy of cancer of the prostate: prognostic criteria and the role of PSA in monitoring]. AB - Progression after radical prostatectomy, evaluated by a rise in plasma PSA and/or the appearance of a pelvic nodule positive on biopsy and/or the presence of bone metastases confirmed by bone scan, was studied in a series of patients with prostatic cancer with a follow-up of between 6 months and 5 years. The progression-free survival rate was 86% at 1 year and 60% at 5 years. A progression-free survival rate and the relative risk of progression were established on the basis of the morphological characteristics (anatomical stage, tumour volume, seminal vesicle invasion, condition of the prostatic capsule and lymph nodes, positive resection margins at the apex) and histological features (Gleason's score) of the cancer, allowing determination of the influence of prognostic criteria on the outcome. The positive resection margins at the apex were due to preservation of the nervi erigentes. The preservation of the neurovascular pedicles may not be justified in the case of a tumour confined to the prostatic apex. PMID- 1284387 TI - [Benign and malignant Brenner tumor of the ovary: a clinicopathological and immunohistochemical study]. AB - The clinicopathological and immunohistochemical features of 7 cases of benign and malignant Brenner tumor of the ovary, including 5 benign and 2 malignant tumors are described. Microscopically, all of the benign cases were composed of both epithelial nest and fibrous stroma. Two cases of the malignant Brenner tumor showed that the histologic features resembled the structure of non-keratinized squamous carcinoma or transitional cell carcinoma. Immunohistochemistry showed that tumor cells of the epithelial nest were keratin and EMA positive in 7 cases; CEA-positive in 5 cases; and negative in 2 cases of benign Brenner tumor. The results indicated that Brenner tumor is an epithelial neoplasm in nature. The diagnostic criteria and histogenetic origin are discussed. PMID- 1284388 TI - [Sarcomas of the uterus: immunohistochemical characterization and diagnosis]. AB - Pathologic findings and immunohistochemical characterizations of 18 cases of uterine sarcomas were studied. In endometrial stromal sarcoma (ESS), 5 out of 10 cases had ovarian sex cord-like pattern and 4 out of 10 cases had smooth muscle differentiation. Immunohistochemical findings showed vimentin, desmin and cytokeratin positive in 9/10, 6/10, 2/10 cases respectively which reflects that ESS may differentiate into both epithelium and muscle components morphologically. In malignant mixed Mullerian tumors (MMT), its carcinomatous structure may be positive about vimentin, and its sarcomatous structure may be positive to the epithelium markers, which indicates that both the sarcoma and carcinoma structures have possibly a common origin. It is considered to be of value for the diagnosis of MMT, if the tumor has differentiated both epithelium and mesoderm components or to be positive to myoglobin, NSE* in immunoreaction, accompanying with the morphologic characterizations of the tumor. PMID- 1284389 TI - [The inhibitory effects of catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and DNA polymerases]. AB - Catechin derivatives including (-)-epicatechin gallate (ECG), (-) epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and green tea extract (GTE) were found to inhibit the activities of cloned human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), duck hepatitis B virus replication complexes reverse transcriptase (DHBV RCs RT), herpes simplex virus 1 DNA polymerase (HSV-1 DNAP) and cow thymus DNA polymerase alpha (CT DNAP alpha). EGCG and ECG were shown to be very potent inhibitors of HIV-1 RT. According to the IC50 values for HIV-1 RT, these compounds can be ordered as EGCG 0.0066 mumol/L > ECG 0.084 mumol/L > GTE 0.1 microgram/ml > EGC 7.2 mumol/L. DHBV RCs RT was the least sensitive to these compounds. Kinetic study showed that EGCG exerts a mixed inhibition with respect to external template inducer poly (rA).oligo (dT) 12-18 and a noncompetitive inhibition with respect to substrate dTTP for HIV-1 RT. Bovine serum albumin significantly reduced the inhibitory effects of catechin analogues and GTE on HIV-1 RT. In tissue culture GTE inhibited the cytopathic effect of coxsackie B3 virus, but did not inhibit the cytopathic effects of HSV 1, HSV-2, influenza A or influenza B viruses. PMID- 1284390 TI - [The application of monoclonal antibodies (McAbs) against human serum IgA in single radial immunodiffusion (SRID)]. AB - Among many McAbs to human IgA, two McAbs (A1A10 and A1C9) against two determinants were selected and mixed. They formed opaque precipitation rings with IgA in agarose containing 2% PEG 6000. SRID with our mixed McAbs or PcAbs was used to determine serum IgA concentration in 40 undiluted serum specimens: a comparison of the two showed similar results, with a correlation coefficient of 0.9493 (P < 0.001). We conclude that mixed McAbs A1A10 and A1C9 can replace PcAbs in SRID for the measurement of human total serum IgA. PMID- 1284391 TI - Photosensitivity of 8BrcGMP-induced conductance in ROS-excised patches. AB - Inside-out patches from ROS plasma membranes contain the basic enzymes of the phototransduction cascade. Similar to a native photoreceptor cell, such patches are capable of responding to light, the effect of which suppresses the cGMP activated current. Photoresponses are observed only in the presence of GTP, whereas ATP essentially accelerates the current recovery to a dark level. Photoresponses are also observed in the presence of 8BrcGMP. Phosphodiesterase (PDE) hydrolyzes 8BrcGMP two orders of magnitude slower than cGMP, so the light inhibition of the 8BrcGMP-induced current cannot be accounted for by PDE activation. It seems that activity of cGMP-gated channels depends not only on cGMP concentration, but is additionally controlled by some other regulatory mechanisms. PMID- 1284392 TI - [Hepatocellular adenoma with a high level of alpha fetoprotein. Apropos of a case observed in the Central hospital of Yaounde, Cameroon]. AB - The authors report a case of a young girl aged 23 years, suffering from hepato cellular adenoma associated with a high level of alpha-foeto-protein. The patient after having been operated recovers and the level of alpha-foeto-protein returns to normal. PMID- 1284393 TI - Optical principles of loupes. AB - The use of magnification to improve precision in dental procedures goes back more than a century. However, inadequate understanding of the optical principles employed in the various types of dental loupes can lead to poor fit and adjustment and, eventually, unnecessary eye strain. Eye movement, depth of field, working distance, illumination, crossover point and exit pupil are defined and discussed relative to choosing dental loupes. PMID- 1284394 TI - The anterior single-tooth implant restoration. AB - Placing an anterior single-tooth implant requires thorough planning, informed abutment selection and precise surgical technique. Planning procedures are outlined; abutments, including UCLA's non-segmented, Nobelpharma's single-tooth, CeraOne and non-rotational, implant innovations' pre-angled and non-rotational and DIA's anatomic, are described, with indications and contraindications; and placement considerations are discussed. PMID- 1284395 TI - Precision attachment removable partial dentures. AB - Although added preparations and skill are required to provide precision attachment removable partial dentures, more favorable esthetics and load distribution may outweigh the disadvantages. Basic design principles, categories (intracoronal, extracoronal, stud, bar and plunger) and selection of precision attachments are reviewed. PMID- 1284396 TI - Microscopes in endodontics. AB - The introduction of microscopes in clinical and surgical endodontics is fairly recent. Potential applications, including removal of fractured instruments, localizing calcified canals, soft tissue management and root-end procedures, are reviewed. PMID- 1284397 TI - [The role and therapeutic use of interferons in leishmaniasis (a review of the literature)]. PMID- 1284398 TI - Rapid identification of Actinobacillus actinomycetemcomitans based on analysis of 23S ribosomal RNA. AB - Actinobacillus actinomycetemcomitans is a key microorganism in the pathogenesis of several different forms of periodontal diseases. Identification of this bacterium from clinical specimens may often be complicated by the fact that the colony morphology on TSBV selective medium closely resembles that of Haemophilus aphrophilus and a key differentiating characteristic, catalase reaction, may be variable. Recent genetic studies have shown that the 23S ribosomal RNA molecule is split into two smaller forms in A. actinomycetemcomitans, but is intact in H. aphrophilus. Based on this finding, we describe a new, rapid method for identifying A. actinomycetemcomitans in which single colonies isolated from culture on TSBV agar in 5% CO2 in air are lysed, electrophoresed on 1.5% submarine agarose gels and visualized by staining with ethidium bromide. Using this assay, A. actinomycetemcomitans can be easily distinguished from morphologically similar colonies such as H. aphrophilus strains by differences in 23S rRNA within 2 h. PMID- 1284399 TI - [Biological actions and therapeutic perspectives of double stranded polyribonucleotides: a reappraisal]. AB - Double-stranded polynucleotides, which are composed of two complementary homopolyribonucleotides containing no genetic information, are synthetic molecules capable of mimicking the action of natural double-stranded RNA or viral RNA on cells. Double-stranded polyribonucleotides act as an alarm system alerting the cell to the presence of an external aggression, e.g. a viral attack. In addition, polyribonucleotides have a more active function in that they trigger cell defense processes through activation of a family of genes, of which some encode cytokines, activation of cytoplasmic enzymes involved in antiviral mechanisms or signal transduction, and activation of nonspecific immune responses. Double-stranded polyribonucleotides containing one mismatched base pair per helix have been found to be especially interesting. The best known example is poly(I).poly(C12U), also called ampligen. Poly(I).poly(C12U) is capable, in experimental models, of limiting the development of viruses (including HIV), reducing tumor growth, eliminating metastases, and, according to one report, preventing steady declines in T-cell counts in HIV-positive patients. Therapeutic doses used in the USA as an experimental drug induced little toxicity. In vitro, poly(I).poly(C12U) acts synergistically with interferon, interleukin 2 or AZT, suggesting that these latter drugs may be effective in lower, less toxic doses when used in combination with poly(I).poly(C12U). The therapeutic activity of poly(I).poly(C12U) holds promise. More extensive prospective studies of this agent are warranted. PMID- 1284400 TI - Intraovarian regulation: the IGF-I example. AB - A large body of information now supports the existence of an intraovarian system of insulin-like growth factors (IGFs) replete with ligands, receptors, and binding proteins. The intraovarian IGF system is most likely concerned with the amplification of gonadotrophin hormonal action, other potential regulatory roles remaining speculative at this time. There is every reason to believe that work in the next few years will yield the insight necessary to establish whether or not IGFs are truly indispensable to ovarian function; this remains to be demonstrated through selective ablation of ovarian IGF-I gene expression and the examination of the impact of such manipulation on reproductive potential. PMID- 1284401 TI - [Modulation of ion channel in T lymphocyte activation]. PMID- 1284402 TI - [Effects of amiodarone on kinetics of procainamide and its major metabolite disposition in rabbit]. AB - The effects of steady state amiodarone on the kinetics of procainamide (PA) and its major metabolite, acetylprocainamide (NAPA), disposition in rabbits were examined. When PA was given alone, the pharmacokinetic parameters alpha, beta, Kmo, K1m.V1.V-1m, were 0.20 +/- 0.04, 0.016 +/- 0.003, 0.027 +/- 0.01, and 0.043 +/- 0.02 min-1, respectively. When PA was given in combination with amiodarone, the corresponding values were 0.37 +/- 0.08, 0.0059 +/- 0.002, 0.0096 +/- 0.004, and 0.016 +/- 0.003 min-1, respectively. The results indicated that the disposition kinetics of both PA and NAPA were significantly changed by steady state amiodarone. PMID- 1284403 TI - [Early biological markers of anaphylactoid reactions occurring during anesthesia]. AB - Three markers of in vivo histamine release, i.e. plasma histamine and tryptase, and urinary methylhistamine, were assessed using sensitive radioimmunoassays in 18 patients who had experienced an adverse reaction to an anaesthetic agent. Controls were obtained from 35 patients following a general anaesthetic, which included a muscle relaxant, and who remained free from any adverse reaction. A first blood sample was obtained from all 18 patients a mean 25 +/- 26 min after the reaction, and a second one in thirteen a mean 120 +/- 65 min after the reaction. Ten patients had had a life-threatening reaction. Plasma histamine levels were increased in all these cases, and tryptase concentrations in 9 out of 10. Urinary methylhistamine rarely reached pathological levels (4 out of 10). Skin tests were positive in the four tested patients. Plasma histamine concentration was still high in 8 cases thirty minutes after the reaction, and remained increased for more than 2 h in two patients. Among the other eight patients with a moderate reaction, 3 had high histamine levels, with normal or weakly increased tryptase concentrations, and normal urinary methylhistamine. Two of these patients had positive skin tests. There were no abnormal findings in any of the investigations carried out in the other five patients, except for a slightly positive skin test to atracurium in one patient. Plasma histamine had a higher sensitivity than tryptase levels. Methylhistamine concentrations were only rarely of interest. There were no false positives with the three investigated markers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284404 TI - Combined bromodeoxyuridine immunohistochemistry and Masson trichrome staining: facilitated detection of cell proliferation in viable vs. infarcted myocardium. AB - Cells in the S-phase of the cell cycle can be identified in tissue sections by immunohistochemical localization of the thymidine analogue bromodeoxyuridine (BrdU). Generally, a single counterstain is used to visualize the underlying tissue; however, interpretation of morphologic detail is often difficult. We have utilized BrdU to localize proliferating cells in myocardium exposed to angiogenic mitogens. To facilitate identification of labelled nuclei in the context of infarcted vs. viable myocardium, BrdU immunohistochemistry was followed by a modified Masson trichrome stain. The time of exposure to the counterstains and the wash protocol were re-revised, permitting clear identification of the labelled brown nuclei against a background of red viable myocardium vs. blue infarct. The combined technique also provides color contrast suitable for computer-based image analysis. PMID- 1284405 TI - Golgi method without osmium tetroxide for the study of the central nervous system. AB - A variant Golgi technique was developed that consisted of substituting osmium tetroxide with formaldehyde as the initial fixative in intracardiac perfusion, along with the addition of glacial acetic acid to the chromating fluid. This procedure avoids disposal of dangerous waste substances into the environment. Other advantages include 1) reduction of cost, danger to lab workers, and risk of disruption of the tissue slices during their handling by eliminating the osmium tetroxide, 2) clear tissue background, 3) greater quantity of impregnated neurons than in the classical procedure, with distinct morphological details easily identified even in gross sections and 4) reduction in processing time. PMID- 1284406 TI - Anti-centromere antibody and CREST syndrome in patients with primary biliary cirrhosis. AB - Anti-centromere antibodies (ACA) in 41 sera from patients with primary biliary cirrhosis (PBC) were analyzed by an immunoblotting method and the correlation between the presence of ACA and the clinical features in these PBC patients was studied. In 10 of 16 ACA-positive PBC patients, one or more clinical features of CREST syndrome (PBC-CREST) were found. Statistical differences were observed in age at disease onset, serum levels of IgM and total bilirubin and titer of anti M2 antibody, between PBC-CREST patients and the PBC patients without CREST symptoms (PBC-non CREST). By immunoblotting analysis, three major epitopes of ACA were identified at 18 kD, 80 kD and 140 kD polypeptides. The 18 kD polypeptides were detected in all 16 ACA-positive PBC patients. From these results, it is suggested that ACA-positive PBC-CREST patients can be separated from ACA-negative PBC-CREST and PBC-non CREST patients. PMID- 1284407 TI - Primary mediastinal diffuse large cell lymphoma initially presented with pericardial infiltration. AB - A 33-year-old Japanese woman visited our hospital with progressive dyspnea. A chest roentgenogram and a chest computed tomogram revealed a mediastinal tumor and pericardial effusion. Ultrasound cardiography revealed the existence of cardiac tamponade. She was successfully treated with emergency pericardial drainage, thoracocentesis and chemotherapy. The histological diagnosis of diffuse large B cell lymphoma was established with the tumor specimen obtained by transcutaneous fine needle aspiration biopsy and through immunohistochemical analysis. This is a rare case of primary mediastinal diffuse large cell lymphoma with initial presentation of a symptom related to pericardial effusion. PMID- 1284408 TI - Polysaccharide storage myopathy associated with recurrent exertional rhabdomyolysis in horses. AB - A polysaccharide storage myopathy is described in nine Quarterhorses, Quarterhorse crossbreds, American Paints and Appaloosa horses which had a history of recurrent exertional rhabdomyolysis. Muscle biopsies were characterized by high muscle glycogen concentrations with up to 5% of type 2 muscle fibers containing inclusions which stained positively with the periodic acid Schiff (PAS) stain. The inclusions were classified as an acid mucopolysaccharide, based on their histochemical staining characteristics. Ultrastructural studies revealed that the inclusions were composed of beta glycogen particles interspersed among arrays of filamentous material. In addition, many type 2 fibers contained multiple subsarcolemmal vacuoles. These vacuoles stained lightly with eosin and did not stain positively with PAS. Centrofascicular atrophy and necrosis of scattered type 2 fibers were present in biopsies from some horses. No glyco(geno)lytic enzyme deficiencies were identified using a biochemical screening test for anaerobic glycolysis. Attempts to measure branching enzyme activities in both affected and control samples were unsuccessful, employing methods developed for human muscle. The polysaccharide accumulation in these horses may represent a hereto yet undefined metabolic disorder of skeletal muscle. PMID- 1284409 TI - [Neurohormonal regulation of the development and regenerative processes of bone and cartilage tissues]. AB - Neurohumoral regulation of cartilaginous and osseous tissues was investigated in different stages of ontogenesis. It has been shown that these tissues are targets practically for all hormones produced by the body. The reciprocal reaction of osseous and cartilaginous tissues to different concentrations of hormones was estimated. It has been also demonstrated that the action of hormones in these tissues manifests itself in accordance with the general regularities and that their effects are strictly specific for the test target tissues. An opinion is advanced about the breach of the endocrine situation in the body as a risk factor of the development of dystrophic processes in cartilages. PMID- 1284410 TI - [Hereditary (dysplastic) diseases of the joints]. AB - Using the intentional procedures to reveal systemic semantic interrelations between different phenomena that form the causative-sequential chain in joint diseases of dysplasia genesis and assuming the pathology theory laws as a basis, applying the methodologies of different interdisciplinary sciences and the technology of cognitive simulation, the conceptual model "joint dysplasia- dysplasia arthrosis" was developed. This model depicts the characteristic features of joint dysplasia. The use of the model permitted one to base and describe a group of inherited (depressional) diseases of joints as an independent scientific orthopedo-arthrological problem. The application of the conceptual model confirmed its high cognitive and reforming role. Using this model on a knee joint new syndromes of dysplasia have been described; the system of roentgenometric diagnosis of dysplasia anomalies and new methods of surgical intervention have been elaborated; the foundation has been laid of prophylactic surgery aimed at the exclusion or at the minimizing of the risk of gonarthrosis in persons suffering from different inherited syndromes. PMID- 1284411 TI - [Stress and the body]. AB - The paper deals with new data on the influence of stress on the neurophysiological, hematological, cardiological, hormonal and trophic processes occurring in the body of man and animals. Experimental emotional stresses which offer an opportunity to effectively explore systemic stressful reactions are described. It is shown that neurogenic stress plays the pathogenic role in the onset of blood disorders, in activation of the adrenergic system, and in disorders of the conduction system of the heart. Emphasis is laid on the processes of dystrophy and destruction in osseous and cartilaginous elements of the bones and joints. The author base the role of emotional stress (according to P. K. Anokhin) in the genesis of diseases of motion organs (osteochondrosis, arthrosis, parodontosis). PMID- 1284412 TI - [Pathological changes induced by environmental chemical pollutants in tissues of the locomotor system]. AB - The most widespread contaminants that accumulate in the environment due to the activity of man are mercury, lead, phenol and sulphur compounds. They have a harmful effect on the body and to an even greater extent on its progeny. A study was made of structural and functional changes in supporting (hyaline cartilage, bone) and hemopoietic (bone marrow) tissues under conditions of lead and phenol poisoning of albino rats and guinea pigs. The methods applied were histochemistry, historadiography, and electron microscopy. It has been established that lead can be accumulated by tissues (particularly by cartilage and bone), inducing disorders of plastic and energy metabolism in the cell. This is attended by the growth delay, osteoporosis and inhibition of normal and reparative osteogenesis. The toxic effect of phenol on the cells manifests by inhibition of the enzymic activity; there is evidence of disturbance of oxidative phosphorylation and of the mechanisms of specific biosynthesis and energy metabolism in the cells. Under conditions of phenol intoxication the chondrocytes and osteoblasts show disorders in the biosynthesis of collagen and sulphated glycosaminoglycans with an evident disproportion of their macromolecules in the cartilage and bone matrix. PMID- 1284413 TI - [New approaches to developing drugs with cartilage protective properties]. AB - The conjuncture and technological analysis was made of the current status and approaches to further development of the drugs--chondroprotectors on the basis of glycosaminoglycans. The concept of the goal-oriented search of the new type of drugs for the treatment of diseases of joints and other pathologies was worded on the basis of the systematization and summarization of the reported data and the results of own investigations. This concept rests on the current views of biochemistry of the nature of metabolism and the mechanisms of its regulation. The approach suggested lies in obtaining specific products--protein fragments (polypeptides) that contain oxidized functional groups not found, as a rule, under natural conditions in normal physiological state. The conversion of protein fragments to a higher degree of oxidation means the conversion to the metabolic state in which the possibility of regulating disturbed metabolism is provided. In order to realize the given approach, it is proposed that the oxidation-hydrolytic modification of human placenta may be performed with the aid of chlorine dioxide or direct synthesis. The results of studying the physicochemical and pharmacological properties of the products obtained are presented. Animal experiments have demonstrated a powerful hitherto unknown pharmacotherapeutic action in a dose of 0.3 mg/kg, namely chondroprotective, resolving, reparative, antiinflammatory, antioxidant, analgesic, antistress, and immunotropic. The regulatory mechanism of the action of the substances obtained is suggested. PMID- 1284414 TI - [Coxarthrosis: clinical aspects, diagnosis and treatment]. AB - Based on a large clinical material the authors analyze the causes of the development of secondary coxarthrosis, suggest new methods of the surgical treatment of the disease, worked out at the Pathology Clinic of Large Joints, Prof. M. I. Sitenko Kharkov Research Institute of Orthopedics and Traumatology, with regard to the shortcomings of the common treatment methods. The term "hyperplastic coxarthrosis" is introduced, the treatment method for that pathology is offered. The problem of further studies and of the design of new methods for the treatment of chronic nonspecific coxitis is under discussion. PMID- 1284415 TI - [Lumbar spondylarthrosis]. AB - The results are presented of pathomorphological studies and clinical examinations of 572 patients with lumbar zygo-apophyseal joint arthrosis using arthrography, intraarticular treatment- and- diagnostic blockades, intracutaneous joint denervation and surgical treatment of arthrogenous lumbar canal stenosis. Based on the data obtained, the pathogenetic classification of lumbar spondyloarthrosis has been elaborated and presented in the given paper. PMID- 1284416 TI - [Current status and prospects of studying vertebrogenic diseases of the peripheral nervous system]. PMID- 1284417 TI - [Angiography in the differential diagnosis of mono-oligo-arthritides in children and adults]. AB - The results of the use of angiography in the diagnosis of chronic mono oligoarthritides are summarized. The author provides the data on 113 patients aged 2 to 50 years, in whom the diagnosis was confirmed histologically. Describes the angiographic appearance of synovial sarcoma, pigmented villonodular synovitis, juvenile chronic arthritis, juvenile rheumatoid arthritis, tuberculous gonitis, chondromatosis, chondroblastomas, post-traumatic synovitis, hemangiomas, and reactive synovitis in the articular form of osteoid osteoma. The use of angiography improved the radiodiagnosis of mono-oligoarthritides by 45.8%. The conclusion is made that in accordance with indications, angiography may be used as a modality in the system of all-round examination of patients suffering from chronic mono-oligoarthritides. PMID- 1284418 TI - [Contact radiotherapy of rheumatoid arthritis]. AB - The authors have devised a method of contact radiotherapy with open radionuclides (198Au) to be used in the treatment of patients suffering from rheumatoid arthritis. Indications for therapy have been defined. In 360 patients suffering from rheumatoid arthritis, radioactive colloid gold was administered to the affected joints. The therapeutic effect was slow in development. The best clinical results were recorded at month 12. Considerable improvement was noticed in 70% of the patients, improvement in 20%, and in 10% of the patients, no therapeutic effect could be recorded. Good effect was ascertained in patients with X-ray Stage I and II disease (70%). PMID- 1284420 TI - [Restoration of movement in the joints with the aid of a hinge-distraction apparatus]. AB - The device described presents an external hinge which is fixed by transosseous wires and reproduces as far as possible the normal kinematics of the joint. By removing all load from the joint surfaces and maintaining a constant predetermined space between them, the apparatus eliminates friction, prevents pain and muscle spasm, and minimizes abnormal mobility (or instability). It also permits gradual and controlled reduction of old traumatic or congenital dislocations or contractures. Once the bones are in proper relationship, the apparatus permits graduated, controlled, nearly frictionless motion about the correct axis so that a good range of motion is restored and joint surfaces of the proper shape are formed. Finally, ununited fractures close to the joint surface may be immobilized while joint motion is permitted. Experience gained with the apparatus has shown that the method described is physiological and not difficult, complications associated with its use being rare and not serious. The good results obtained with the use of the apparatus warrant its wider application. PMID- 1284419 TI - [Joint prosthetics using carbon implants]. AB - A group of "Intost" materials based on carbon were developed by the I. M. Sechenov Moscow Medical Academy jointly with the Research Institute of Graphite. After experimental studies the materials were authorized for use in clinical practice for implantation. A concept of the design of endoprostheses of the joints from "Intost" was developed, on the basis of which unipolar combined endoprostheses of the hip joint (127 cases), metatarsophalangeal articulation (27 cases), humeral and metacarpophalangeal articulations (two cases each), and condyles of the tibia (5 cases) were made and applied in clinical practice. A detailed analysis is given of ten years of experience gained with the use of the combined unipolar endoprosthesis of the hip joint manufactured from "Intost-1" and "Intost-3". Long-term beneficial results were obtained in 95% of patients. Endoprosthesis is recommended for the treatment of fractures and false joints of the neck of the femur in elderly and senile patients. PMID- 1284421 TI - [Recombination (regroupings), an important mechanism of quantitative changes in live systems]. AB - In natural phenomena a new quality may occur not only in the course of qualitative changes but also by means of different recombinations (regroupings) of the elements that constitute a system, without any change in their number. Different versions of such regroupings are discussed. Recombination (conformation) changes, widely spread in live nature in particular, are of paramount importance, playing a role in the realization of a wide range of adaptation reactions of the body. PMID- 1284422 TI - [Changes in creatine kinase activity and protein spectrum of the developing muscle culture treated with creatine phosphate]. AB - A study was made of the influence of creatine phosphate (CP) on creatine kinase activity and the total protein status of the primary chicken myoblast culture. It has been established that the two-hour exposure of the developing culture in the presence of 2 and 4 mM CP is accompanied by the lowering of the content of water extractable protein and a considerable increase of creatine kinase activity. Meanwhile the total activity of the enzyme rises in the non-differentiated and falls in the differentiated one. Electrophoretic analysis has shown CP to produce not only quantitative but also deep qualitative changes in the myoblast protein spectrum. It is assumed that the changes revealed are nonspecific. PMID- 1284423 TI - [Systemic concepts of real complexity of the organization of the joints]. AB - Cognitive problems arising in arthrology due to discrepancies of analytical means of high complexity as regards the object under examination are analyzed. The use of systemic analysis opens up possibilities of overcoming these difficulties since it permits one (a) to understand specific conformities to natural laws caused by the integrity of the locomotor apparatus and its joints organization, thus affording one to reveal connections between the structure, metabolism, blood supply and joint function in health and disease; (b) to overcome difficulties in interdisciplinary mutual understanding and realization of various knowledge integration on the basis of systemic simulation of the integral object; (c) to arm arthrology with the methodology of task force and goal-oriented planning and organization of multidisciplinary all-round investigations on the basis of integral vision and theoretical analysis of large-scale problems. PMID- 1284424 TI - Synthesis and secretion by mouse 3T3 cells of an inhibitor of cell growth (mIGFBP 3): correlation with cell proliferation. AB - Our results show that stimulation by serum of dense cultures of 3T3 cells rapidly induced increased synthesis of a growth inhibitor (mIGFBP-3) capable of binding IGF. mIGFBP-3 was secreted by stimulated cells immediately after its synthesis, and accumulated in the medium. Accumulation of mIGFBP-3 in the medium increased, as a function of growth factor (bFGF, PDGF, insulin) concentrations and time. bFGF was the best stimulatory factor for both DNA synthesis and accumulation of mIGFBP-3 in the first 24 h of incubation. DNA synthesis was arrested after 48 h of incubation with bFGF when accumulation of mIGFBP-3 was maximal. Since we showed that mIGFBP-3 is able to inhibit bFGF stimulation of DNA synthesis in mouse fibroblasts, it is possible that the accumulation of mIGFBP-3 induces a feedback regulation of cell growth. PMID- 1284425 TI - Changes in the ribonucleoprotein constituents of the nucleus during the differentiation of muscle cells in the chick embryo. AB - The ribonucleoprotein components of the nucleus of chick embryo muscle cells in different stages of development were studied by electron microscopic quantitative stereology. The changes of the constituents were related with the appearance of the innervation by means of silver impregnation for light microscope. The numerical density of the perichromatin granules (PCG) is low in mononuclear cells and myotubes. It is noteworthy that the frequency of the PCG does not change during the transition of the cells in mitotic cycle to postmitotic myoblasts and during myofibril differentiation. However, there is an important increment in this parameter when the motor nerve fibers arrive at the muscle and the synaptic contacts are established. This change is correlated with appearance, or at least with a great increase, of the importance of posttranscriptional controls of the expression of some genes. The augmentation in the frequency of PCG is not accompanied by alterations of the abundance of total RNP particles, in close resemblance with the phenomena occurring in neuroblast during the differentiation of synaptic endings. The variations of the nucleolar volume coincide with the changes in rRNA synthesis. PMID- 1284426 TI - Studies of the molecular biology of parathyroid hormone-like peptide. AB - Molecular biology techniques have been used to examine alternative splicing of the PLP gene, interspecies homology of PLP, the genetic relationship of PLP and PTH. Molecular biology approaches can also be successfully employed to examine both the regulation of PLP production and its function both in emulating PTH and in non PTH-related actions. PMID- 1284427 TI - Cystatin C based peptidyl diazomethanes as cysteine proteinase inhibitors: influence of the peptidyl chain length. AB - The peptidyl diazomethanes Cbz-Gly-CHN2, Boc-Val-Gly-CHN2, H-Leu-Val-Gly-CHN2, Cbz-Leu-Val-Gly-CHN2 and Cbz-Arg-Leu-Val-Gly-CHN2, with peptidyl portions modelled after the proposed cysteine proteinase interacting N-terminal segment of human cystatin C, were synthesized. Their efficiency as cysteine proteinase inhibitors was tested against papain, human cathepsin B and bovine cathepsin B. All, except Cbz-Gly-CHN2, were found to be irreversible inhibitors of the tested enzymes. Each addition of an amino acid residue to their peptidyl portions resulted in an increased inhibition rate of all three enzymes. These data suggest that the arginyl residue of the tetrapeptidyl diazomethane, and also the corresponding arginyl residue in native cystatin C, interact with a S4 substrate pocket subsite of both papain and cathepsin B. The most efficient inhibitor, Cbz Arg-Leu-Val-Gly-CHN2, inhibited papain and cathepsin B with rate constants of the same order of magnitude as those for L-3-carboxy-trans-2,3-epoxypropionyl leucylamido-(4-guanidin o)butane (E-64). The high water-solubility of Cbz-Arg-Leu Val-Gly-CHN2 allowing it to be dissolved to molar concentrations without use of non-physiological additives, makes it suitable for in vitro and in vivo cysteine proteinase inhibition studies. PMID- 1284428 TI - Beta-lactams: a new class of conformationally-rigid inhibitors of gamma aminobutyric acid aminotransferase. AB - A structural similarity of several monobactams (2-4), 3-aminonocardicinic acid (6), 6-aminopenicillanic acid (7), 7-aminocephalosporanic acid (8), and 7 aminodesacetoxycephalosporanic acids (9, 10) to gamma-aminobutyric acid (GABA) and to known inhibitors and substrates of GABA aminotransferase is described. Because of this, the above-mentioned compounds were tested as competitive inhibitors and as inactivators of pig brain GABA aminotransferase. All of the compounds were competitive inhibitors of GABA aminotransferase. On the basis of the inhibitory potency of these conformationally-rigid GABA analogues it is hypothesized that GABA is bound at the active site with its amino and carboxylate groups in a syn orientation. None of the compounds inactivates GABA aminotransferase. These beta-lactam analogues represent the first examples of a new class of inhibitors of GABA aminotransferase. PMID- 1284429 TI - Inhibition of human alpha-, beta- and gamma-thrombin by mono-, bis-, tris- and tetra-benzamidine structures: thermodynamic study. AB - The inhibitory effect of mono-, bis-, tris- and tetra-benzamidine structures (benzamidine, DAPP, TAPB and TAPP, respectively) on the catalytic properties of human alpha-, beta- and gamma-thrombin (alpha-, beta- and gamma-thrombin, respectively) was investigated (between pH 2.0 and 7.0, I = 0.1 M; T = 37.0 +/- 0.5 degrees C). The affinity of DAPP, TAPB and TAPP for alpha- and beta-thrombin is higher than that found for benzamidine association around neutrality, converging in the acidic pH limb; in contrast, benzamidine, DAPP, TAPB and TAPP show the same value of the association inhibition constant (Ki; M-1) for gamma thrombin over the whole pH range explored. On lowering the pH from 5.5 to 3.0, the decrease in affinity for benzamidine binding to alpha-, beta- and gamma thrombin, as well as for DAPP, TAPB and TAPP association to gamma-thrombin reflects the acidic-pK shift, upon inhibitor binding of a single ionizing group. On the other hand, values of Ki for DAPP, TAPB and TAPP binding to alpha- and beta-thrombin appear to be modulated by the acidic-pK shift, upon inhibitor association, of two equivalent proton-binding residues over the same pH range. By considering molecular models of the serine proteinase:inhibitor complexes, the observed binding behaviour of benzamidine, DAPP, TAPB and TAPP to alpha-, beta- and gamma-thrombin has been related to the inferred stereochemistry of the enzyme:inhibitor contact region(s). PMID- 1284430 TI - Effects of 4-hydroxyandrost-4-ene-3,17-dione and its metabolites on 5 alpha reductase activity and the androgen receptor. AB - The steroidal aromatase inhibitor, 4-hydroxyandrost-4-ene-3,17-dione (4OHA) and its metabolites, 4-hydroxytestosterone (4OHT), 3 beta,17-dihydroxy-5 alpha androstan-4-one (metabolite A) and 3 alpha, 17-dihydroxy-5 beta-androstan-4-one (metabolite B) were evaluated as inhibitors of the human prostatic 5 alpha reductase enzyme and for binding to the rat prostatic androgen receptor. 4OHA and 4OHT were weak inhibitors of 5 alpha-reductase with IC50 values of 15-29 microM. Metabolites A and B had no significant inhibitory activity. 4OHA and metabolites A and B bound weakly to the androgen receptor. The binding affinities (RBA) relative to mibolerone (RBA = 100) were 0.085, 0.485 and 0.016, respectively. However, 4OHT (RBA = 75) was a more potent binder than the endogenous androgen 5 alpha-dihydrotestosterone (RBA = 66). The ability of these metabolites, in particular 4OHT, to bind to the androgen receptor may explain the in vivo androgenic activity of 4OHA. PMID- 1284431 TI - Irreversible inhibition of thymidylate synthase by pyridoxine (B6) analogues. AB - Three vitamin B6 analogues have been synthesized and tested as inhibitors of thymidylate synthase. The compounds are: 4',5'-dichloro-, 4',5'-dibromo- and 4',5'-diiodo-pyridoxine. All three analogues inhibited the enzyme irreversibly. The kinetic data for the chloro- and bromo-analogues showed that a limiting rate of inhibition is approached as the inhibitor concentration is increased, which indicates that a reversible enzyme:inhibitor affinity complex is formed prior to the irreversible reaction. 4',5'-Dibromo-pyridoxine exhibited a greater binding affinity (lower Ki) for thymidylate synthase than 4',5'-dichloro-pyridoxine, and it also reacted faster to irreversibly inhibit the enzyme. The presence of the substrate dUMP (10 microM) completely protected thymidylate synthase from inhibition. These data suggest that the halogenated vitamin B6 analogues are active site-directed inhibitors of thymidylate synthase, which first bind reversibly to the catalytic site and then react irreversibly with the enzyme. PMID- 1284432 TI - 5838-DNI, a deoxyribonuclease inhibitor produced by Streptomyces sp. strain no. A 5838. AB - 5838-DNI, an inhibitor of deoxyribonuclease (DNase) II from porcine spleen was produced by Streptomyces sp. strain No. A-5838. The structure of 5838-DNI was shown to be 1,4,4a,5,12,12a-hexahydro-4,4a,11,12a-tetrahydroxy-3,8-dimethoxy-9- methoxycarbonyl-10-methyl-1,5,12-trioxo naphthacene. Although similar in structure to tetracenomycin C, which is an antibiotic against Gram-positive bacteria, 5838-DNI has different antibacterial activity. 5838-DNI was distinguished from 5923-DNI, a previously reported DNase II inhibitor, in inhibitory activity against each enzyme. 5838-DNI showed dependency of inhibition on pH and temperature, and inhibited phosphodiesterase I in a competitive manner. These data suggest that 5838-DNI is the first reported example of an inhibitor of microbial origin which is able to inhibit DNase II and phosphodiesterase I. PMID- 1284433 TI - Novel inhibitors of enkephalin-degrading enzymes. IV: Structure-activity relationships within the penicillins as enkephalinase inhibitors. AB - A range of penicillins have been examined as competitive reversible inhibitors of enkephalinase (neutral endopeptidase; EC 3.4.24.11). Carfecillin (Ki = 0.18 microM) was the most potent inhibitor in the series, whereas cloxacillin (27.5 microM), ampicillin (41.0 microM), nafcillin (58.7 microM) and carbenicillin (158 microM) had moderate potency and benzyl penicillin (885 microM), mezlocillin (473 microM) and azlocillin (556 microM) were weak inhibitors. Structure-activity relationships within the series have been rationalised from a consideration of molecular graphics analysis of the match between receptor binding groups with thiorphan as well as log P values. PMID- 1284434 TI - Purification and characterization of invertase inhibitors from Dioscorea rotundata tuber. AB - Three invertase inhibitors (A), (B) and (C) from Dioscorea rotundata tuber were resolved on DEAE-cellulose ion exchanger. Two of the inhibitors, (B) and (C), were proteins and homogenous on polyacrylamide gels Mr 21,000 +/- 85 and 26,982 +/- 40/36,307 +/- 50 respectively. The inhibitors (B) and (C) were inactivated at 60 degrees C and had activity-pH optima at 5.2 and 6.4 respectively. (B) and (C) were non competitive inhibitors of invertase from yam and other sources. PMID- 1284435 TI - Increased urinary excretion of urine protein 1 induced by L-arginine monohydrochloride. PMID- 1284436 TI - Sex- and age-dependent reference values of alpha-1-microglobulin in urine. PMID- 1284437 TI - Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse. AB - Intrathecal injection of N-methyl-D-aspartate (NMDA) induces a short duration hyperalgesia in mice. An inhibitor of nitric oxide synthase (NOS), N omega-nitro L-arginine methyl ester (L-NAME), administered either systemically or intrathecally, blocked the NMDA-induced hyperalgesia. This effect was partially reversed by the NOS substrate, L-arginine. Intrathecal hemoglobin mimicked the effects of L-NAME. Intrathecal injection of the NO-donating compounds, sodium nitroprusside (SNP) and hydroxylamine, resulted in a hyperalgesia that lasted 3 h and was reduced by coadministration of hemoglobin. Thus, nitric oxide production appears to mediate NMDA-induced hypersensitivity and may contribute to other forms of centrally induced hyperalgesia. PMID- 1284438 TI - Neonatal nerve growth factor treatment alters the preganglionic innervation pattern of rat superior cervical ganglion. AB - We treated rat pups with nerve growth factor (10 micrograms/animal/day s.c.) over postnatal days 1-7. Subsequent adult neuron numbers and tyrosine hydroxylase content in superior cervical ganglion were normal, but preganglionic inputs, as gauged from ganglionic choline acetyltransferase, were reduced. In parallel, intraganglionic axon terminals containing calcitonin gene-related peptide, but not those containing substance P, were increased in number. We postulate that neonatal nerve growth factor stimulates sprouting of ingrowing axons that have entered the ganglion soon after birth and that this represses subsequent establishment of cholinergic preganglionic synapses. PMID- 1284439 TI - Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. AB - The distribution of nitric oxide synthase (NOS) immunoreactivity was investigated in the guinea-pig small intestine. There were many immunoreactive nerve cell bodies in the myenteric plexus but very few in submucous ganglia. NOS immunoreactivity was not found in non-neuronal cells except for rare mucosal endocrine cells. Abundant immunoreactive nerve fibres in both myenteric and submucous ganglia, and in the circular muscle, arose from myenteric nerve cells whose axons projected anally along the intestine. NOS immunoreactivity coexisted with VIP-immunoreactivity, but not with substance P immunoreactivity. We conclude that nitric oxide synthase is located in a sub-population of enteric neurons, amongst which are inhibitory motor neurons that supply the circular muscle layer. PMID- 1284440 TI - Ultrastructural studies of medullary synaptic inputs to vasopressin immunoreactive neurons in the supraoptic nucleus of the rat hypothalamus. AB - Direct projections from the A1/C1 catecholaminergic cell group in the caudal ventrolateral medulla oblongata to neurons containing vasopressin (VP) in the supraoptic nucleus (SON) were studied electron microscopically by a double labeling technique which combines anterograde tracing after injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the A1/C1 cell group with VP immunocytochemistry. WGA-HRP-labeled axon terminals originating from neurons in the A1/C1 cell group were found to make synaptic contacts with VP immunoreactive cell bodies and dendrites in the SON, most often forming axo dendritic synapses. This indicates that VP-containing neurosecretory neurons in the SON receive monosynaptic catecholaminergic input from the A1/C1 cell group. PMID- 1284441 TI - Restricted origin and distribution of projections from the lateral to the medial septal complex in rat and guinea pig. AB - The origin and distribution of projections from the lateral to the medial septal complex were studied at the light- and electron-microscopical level in the rat and the guinea pig, with the use of sensitive anterograde tracing techniques. Injections in the lateral septal complex resulted in only weak to moderate labeling in the medial septal nucleus. In contrast, injections in all but the ventral subdivision of the lateral septal complex labeled restricted terminal arborizations in the angular portions of the vertical diagonal band. Analyses at the electron-microscopical level indicated that these fibers form both symmetrical and asymmetrical synapses with dendrites and somata, but not with axons. These findings are discussed in the light of a presumed functional circuit from the hippocampal formation, via the lateral septal complex, to cells in the medial septal complex that originate projections to the hippocampal formation. PMID- 1284442 TI - Phosphorylation sites on tau by tau protein kinase I, a bovine derived kinase generating an epitope of paired helical filaments. AB - Tau protein kinase I (TPKI) isolated from bovine brain has been determined to phosphorylate tau at four distinct sites by detecting modified Ser and Thr residues with protein sequencer. Ser199, Thr231, Ser396 and Ser413 were all found to have been phosphorylated by TPKI (numbering of amino acids was done in relation to the longest human tau [Neuron, 3 (1989) 519-526]). These phosphorylations generate an epitope of PHF (paired helical filaments) and eliminate the recognition of tau by the monoclonal antibody, tau-1. These results suggested that TPKI might be responsible for at least some of the phosphorylation of tau to induce PHF formation. PMID- 1284443 TI - Met-enkephalin-Arg6-Gly7-Leu8- and substance P-containing projections from the nucleus preopticus medianus to the paraventricular hypothalamic nucleus. AB - The nucleus preopticus medianus (POMe) is known to be important for the regulation of fluid balance and cardiovascular control. Direct projections from the POMe to the paraventricular hypothalamic nucleus (PVN), where vasopressin containing neurons exist, were examined in the rat using immunohistochemistry combined with a retrograde tract tracing method. After injection of WGA-HRP colloidal gold into the PVN, many neurons were retrogradely labeled in the POMe; some of them were immunoreactive to Met-enkephalin-Arg6-Gly7-Leu8 (mE8) or substance P (SP). The results indicate that mE8- and SP-immunoreactive neurons in the POMe send their axons to the PVN. PMID- 1284444 TI - Apparent anterograde transport of basic fibroblast growth factor in the rat nigrostriatal dopamine system. AB - Five hours after the stereotaxic injection of approximately 1 ng of [125I]basic fibroblast growth factor (bFGF) into rat substantia nigra (SN), small but consistent amounts of radioactivity were found in the ipsilateral striatum (CP). None was found in the ipsilateral thalamus or contralateral CP, SN or thalamus. The amount found in the ipsilateral CP was very markedly reduced in rats injected 5-7 days after 6-hydroxydopamine-induced lesions of the nigrostriatal dopaminergic tract but was unaffected by prior kainic acid lesion of the CP. No radioactivity was found in the ipsilateral SN 5 h after injections of similar amounts of radioactive bFGF into the CP. These results are consistent with anterograde transport of bFGF in the dopaminergic nigrostriatal tract. PMID- 1284445 TI - Nitric oxide synthase and GABA colocalize in lamina II of rat spinal cord. AB - A dense plexus of fibers in the substantia gelatinosa contains nitric oxide synthase (NOS). Using electron microscopic double-labeling immunocytochemistry for NOS combined with GABA or glutamate, we find that all NOS-positive terminals in this region also contain GABA but are not enriched in glutamate. In an attempt to verify that NOS-positive terminals do not originate from primary afferents, we combined NOS immunocytochemistry with anterograde tracing from the sciatic nerve. An intrinsic spinal origin for the NOS-positive plexus is suggested. The results are discussed in the light of the possible involvement of nitric oxide in hyperalgesia. PMID- 1284446 TI - Histochemical demonstration of NADPH-diaphorase activity, a marker for nitric oxide synthase, in neurons of the rat pancreas. AB - To clarify the role of nitric oxide (NO) in the pancreas, we histochemically investigated NADPH-diaphorase, a marker for NO synthase, in the rat pancreas. NADPH-diaphorase activity was localized in the neurons and endothelium of vessels. The nerve fibers with NADPH-diaphorase activity were observed in both the exocrine and the endocrine pancreas associated chiefly with the vascular systems. Most nerve cell bodies (98.5%) within the pancreatic parenchyma showed strong activity for this enzyme. These results suggest that NO may participate in the hemodynamic control of the pancreas and in the neuronal regulation of pancreatic exocrine and endocrine functions. PMID- 1284447 TI - [Tenascin in breast carcinoma: distribution and significance]. PMID- 1284448 TI - [Pharmacokinetics of procainamide and its metabolite depending on acetylator phenotype]. AB - Procainamide (Pa) and its active metabolite--N-acetylprocainamide (NAPA)- pharmacokinetics was studied in 12 healthy volunteers in relation to acetylation phenotype. Acetylation phenotype was determined with sulphadimidine test. Blood serum levels of PA and NAPA were determined 0.5; 1.0; 1.5; 2.0; 3.0; 4.0; 8.0; and 12 hours following a single oral dose of 500 mg. Blood levels of both PA and NAPA were assayed with immunofluorescence polarization technique (FPIA), using TDx apparatus manufactured by Abbott. Pharmacokinetic parameters were calculated with the aid of pharmacokinetics independent of the model principles. All results were analysed statistically (AWOA). It was found that PA and NAPA pharmacokinetics depends on acetylation phenotype. Blood serum PA levels were higher in slow acetylators during the whole follow-up whereas NAPA levels were lower. Blood serum PA levels in rapid acetylators were decreased while NAPA levels were increased. Acetylation phenotype determined in sulphadimidine test confirmed bimodal procainamide acetylation. PMID- 1284449 TI - Laryngeal hyperplastic lesions, follow-up study and application of lectins and anticytokeratins for their evaluation. AB - A retrospective study of 878 biopsy specimens from 692 patients with laryngeal hyperplastic aberrations was performed according to the Kambic-Lenart classification. Special attention was focused on 88 patients with persistent or recurring disease. In these carcinoma developed in 17 (2.4%) patients, 12 (1.7%) of whom had had atypical hyperplasia. We therefore propose that the term precancerosis, which so definitely implies cancer, should be replaced with the expression risky epithelium where nothing is determined in advance, but a careful follow-up of the patients is imperative. In particular cases of laryngeal hyperplastic lesions, mainly in abnormal and in atypical hyperplasias when the tissue specimens are cut tangentially, the exact identification and position of individual epithelial cells is essential. In such cases histochemical and immunohistochemical methods yield more precise evaluation. Lectins and cytokeratins provide good markers of epithelial maturation. These results contribute to a more useful evaluation of laryngeal hyperplastic lesions, crucial for the choice of adequate therapy. PMID- 1284450 TI - Tenascin in reactive lymph nodes and in malignant lymphomas. AB - Tenascin is an extracellular matrix protein which accumulates in the stroma of various malignant and some benign neoplasms. This has been verified in several immunohistochemical studies. The distribution of tenascin immunoreactivity in lymphatic tissues and neoplasias, however, has not been thoroughly studied. In this investigation we analyzed tenascin immunoreactivity in several benign and malignant lymphatic lesions, including both Hodgkin's and non-Hodgkin's lymphomas. In benign lymph nodes, faint reticular immunoreactivity could be observed in the lymphatic tissue. In benign reactive hyperplasias, a stronger reticular pattern of tenascin immunoreactivity was observed in the interfollicular and medullary areas, while the lymphoid follicles contained only a few positive fibers. A similar immunoreactivity was observed in malignant follicular lymphomas. In diffuse lymphomas, a diffuse meshwork of positively stained fibers was seen. This was also the case for the three cases of Hodgkin's disease of the lymphocyte-predominance nodular subtype. There was no difference in the intensity of the immunoreactivity between benign and malignant disorders. However, in Hodgkin's disease of the nodular sclerosis and lymphocyte-depletion subtypes, a much more pronounced immunoreactivity could be observed in the fibrous septa and the cords. This suggests that the tumor cells are possibly capable of synthesizing growth factors which stimulate fibroblasts to synthesize tenascin. The results indicate that tenascin does not accumulate in the stroma of malignant lymphoid neoplasms with the exclusion of some subtypes of Hodgkin's disease. The distribution of tenascin immunoreactivity in lymphatic tissue is similar to that of the reticular fibers suggesting that the molecules are associated with these structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284451 TI - Effects of testosterone, and testosterone plus estrogen, in the castrated rat ventral prostate--histopathological and immunocytochemical studies. AB - The effects of testosterone (T) and 17 beta-estradiol (E2) on the prostate of castrated rats were investigated by histopathological and immunocytochemical procedures. A significant increase in prostatic weight occurred after 6 weeks treatment with T alone and in combination with E2. The greatest increase in prostatic weight occurred after the administration of T plus E2. Histopathologically, glandular hyperplasia of the prostate was noted, and the number of bromodeoxyuridine (BrdU)-positive cells showed a significant increase over that induced by testosterone alone. PMID- 1284452 TI - [A differential approach to the surgical treatment of liver hemangiomas]. AB - Treatment results and indications for surgery were analysed in 50 cases of hepatic hemangioma versus pattern of hemangiomatosis and size, site and extent of tumor. Surgery was performed in 41 (82%) patients. Radical surgery was possible and justified in as few as one-third of them. Palliative treatment including ligation and roentgen-endovascular occlusion of the hepatic artery and its branches, local ferromagnetic embolization of tumor and suturing and sclerotherapy of hemangioma were performed in 28 cases. End results were analysed in 33 cases followed up to as long as 8 years posttreatment. The extent and type of surgery for hepatic hemangioma should be different for each of the four patterns of the disease identified. PMID- 1284453 TI - [An immunohistochemical method for detecting carcinogenic adducts with DNA]. PMID- 1284454 TI - [Palliative operations in pancreatic cancer]. AB - A procedure of transcutaneous draining of bile ducts through a guided replaceable drain using the gallbladder and formation of cholecystostomy and cholecystohepatico-, gastro entero- and enteroenteroanastomoses is suggested for palliation of pancreatic cancer patients. The procedure offers a good clinical effect assuring a significantly longer survival as compared to standard palliative operations used for pancreatic cancer treatment. PMID- 1284455 TI - [The treatment of nonorganic neoplasms of the lesser pelvis]. AB - In 1967-1989, 330 patients with non-visceral tumors of the small pelvis (children -110 and adults--220) were registered. One hundred and five patients, 17 children included, presented with benign tumors whereas 225 (children--93 and adults--132) -with cancer. Absolute and relative, local and general contraindications to surgery were outlined. The most important criteria are the extent of tumor, patient's status, equipment and surgical skills. Tumors were approached through 9 different accesses depending on their size and site. Surgery wat performed in 242 patients, viz. 89.5% of patients with benign tumors and 65.7% of those with cancer. The percentage of operated children (37.6%) was much lower than that of adults (85.6%) since the former presented with more advanced tumors. Radical surgery was performed in 192 (79.3%) patients; benign tumors were removed in 86.7% whereas cancer--in 44.9%. Complications were encountered in 56.2% of cases, bleeding being the most frequent one (47.0%). Lethality following radical surgery was 3.1%. Radiation and chemotherapy alone proved ineffective. Complex treatment assured better clinical course. One-ten-year survival rate in adults with malignant tumors was 51.2%-31.8%. As few as 17.2% of children survived one year whereas only 6.5%-2 years which points to more aggressive clinical course of malignant non-visceral tumors of the small pelvis in children. PMID- 1284456 TI - [The characteristics of the combined and complex treatment of colloid rectal cancer]. AB - The effectiveness of combined (surgery + radio- or chemotherapy) or complex treatment for colloidal cancer of the rectum was evaluated in 180 patients with such tumors which included mucinous adenocarcinoma, mucinous cancer and signet ring cell cancer. Five-year survival rate in 49 patients treated with adjuvant chemo- and/or radiotherapy (39.9 +/- 9.1%) did not differ significantly from that in cases undergoing surgery alone (39.1 +/- 4.7%) (p > 0.05). PMID- 1284457 TI - [The expression of cytokeratin No. 17 in squamous cell cancer of the cervix uteri: an immunohistochemical study of 19 cases]. AB - Monoclonal antibodies E3 against cytokeratin No. 17 were used for immunohistochemical examination of samples from 19 squamous-cell carcinomas of the uterine cervix and 10 cases of squamous-cell metaplasia of the endocervix. The above antibodies selectively labelled reserve cells of the cervical canal mucosa, basal layer of mature metaplastic epithelium and parabasal and basal cells of immature metaplastic squamous epithelium. In large-cell keratinizing, non-keratinizing and small-cell carcinomas, the expression of cytokeratin No. 17 revealed tendency to basal orientation and was in many respects similar to that in metaplastic squamous epithelium. It was suggested that all the squamous-cell carcinomas studied originated from reserve (metaplastic) cells. PMID- 1284458 TI - Studies on the mechanism of action of the antiparkinsonian drugs memantine and amantadine: no evidence for direct dopaminomimetic or antimuscarinic properties. AB - The effects of the antiparkinsonian drugs amantadine and memantine and of the noncompetitive NMDA receptor antagonist MK-801 were studied in the model of the electrically evoked release of [3H]dopamine and [3H]acetylcholine in slices of the rabbit caudate nucleus in vitro. In the [3H]dopamine release model, high concentrations (> 10 microM) of the drugs investigated showed a marked increase in spontaneous 3H-efflux, with the following order of potency: memantine > MK-801 > amantadine. The spontaneous 3H-efflux induced by 50 microM memantine was diminished by pargyline (10 microM), but was insensitive to the presence of tetrodotoxin (0.3 microM), or nomifensine (1 microM), or to the omission of Ca2+ in the superfusion medium; in the absence of nomifensine it consisted mainly of 3H-metabolites of dopamine. The latter findings indicate that the memantine induced spontaneous 3H-efflux is unrelated to the firing of striatal interneurons but point to a direct releasing effect of memantine on dopaminergic storage granules. On the other hand, the electrically evoked release of [3H]dopamine seemed to be unaffected by memantine, was only slightly reduced by amantadine but significantly inhibited by MK-801. In the model of the electrically evoked release of [3H]acetylcholine, only MK-801 (> 50 microM) showed significant inhibitory effects, both on spontaneous and evoked overflow of [3H]acetylcholine; the effects of memantine and amantadine were negligible. Since only high concentrations of amantadine and memantine (exceeding those which, according to the literature, may be reached in vivo) showed effects in the present in vitro dopamine and acetylcholine release models, it is concluded that the clinical efficacy of these antiparkinsonian drugs is most probably unrelated to an enhancement of dopaminergic transmission as suggested from earlier in vitro and in vivo findings. The higher activity of MK-801 in the present model and the recent observation that both memantine and amantadine bind--although with lower affinity--to an MK-801 binding site in the NMDA receptor-linked ion channel, suggest a possible involvement of striatal NMDA receptors in the antiparkinsonian effects of these drugs. PMID- 1284459 TI - Differences in cardiodepressant effects of halothane and isoflurane after inotropic stimulation in guinea-pig papillary muscles. AB - The effects of halothane and isoflurane on action potentials and force of contraction were studied in guinea-pig isolated papillary muscles in order to investigate the cardiodepressant action of the anesthetics in the presence of clinically relevant inotropic drugs. In control conditions, equipotent concentrations of the two volatile anesthetics depressed force of contraction to a similar degree. Halothane (2%) slightly shortened the action potential duration, whereas isoflurane (2.8%) did not influence the shape of the action potential. The muscles were then treated with three different inotropes, digitoxin, amrinone and 3-isobutyl-1-methylxanthine (IBMX) prior to exposure to the anesthetics. After pretreatment with digitoxin and amrinone, halothane was significantly more cardiodepressant than isoflurane. With IBMX, no difference in negative inotropic effect was observed. Neither volatile anesthetic significantly changed the action potential duration after pretreatment with the inotropic drugs. We suggest that halothane is more cardiodepressant than isoflurane in the presence of drugs which enhance force of contraction both by an increase in calcium influx and calcium release because it impairs force of contraction not only via inhibition of the calcium current but also via interference with calcium release. PMID- 1284460 TI - [Familial polymorph ventricular extrasystole associated with Pierre Robin syndrome]. AB - In a family of 9 persons over 3 generations, 6 had incessant polymorphic ventricular extrasystoles, often in salves, resembling unsustained bidirectional ventricular tachycardia. Ventricular repolarisation was abnormal with giant U waves. Five persons had suffered syncopes. All had a facial abnormality: one woman had a complete Pierre Robin syndrome with mandibular hypoplasia, glossoptos and cleft palate; in the other cases, minor forms were observed, with micrognathia and ogival palate. Two patients had bone abnormalities of the feet with total agenesis of the last 2 phalanges of several toes. This familial polymorphic ventricular extrasystole with repolarisation abnormalities has many features in common with the congenital long QT syndrome; associated with the Pierre Robin syndrome and bone abnormalities of the extremities it would seem to be a new multiple congenital abnormalities syndrome. PMID- 1284461 TI - [Specific disorders of mental development]. PMID- 1284462 TI - Three separate epitopes on human IFN-alpha variants defined by monoclonal antibodies and their role in the binding to receptors. AB - Two monoclonal antibodies (mAbs) designed 9-1-1 and 2-2-1, produced by murine hybridoma clones, raised to recombinant IFN-alpha 2c and one mAb, designed 3A3-2, raised to recombinant IFN-alpha 88, have been characterized with respect to neutralization of IFN antiviral and antiproliferative activities. The regions of IFN molecule which these antibodies are directed against have been defined by analyzing cross- reactivity with four IFN-alpha subtypes (IFN-alpha 88, IFN-alpha 2a, IFN-alpha 2b, IFN-alpha 2c) and two fragments of IFN-alpha 88. An analysis of cross-reactivity patterns with IFN-alpha 88 and IFN-alpha 2c indicated that 3A3-2 mAb was directed to an epitope on IFN-alpha 88 not overlapping with epitopes of other mAbs, however its localization was not exactly defined. The epitope recognized by 9-1-1 mAb was present on IFN-alpha 88 and IFN-alpha 2c, and also was not overlapping the epitopes of other mAbs. Using another variant IFN-alpha 2a, containing Lys instead of Arg at position 23, for competitive binding study it was shown that Arg 23 was implicated in the epitope recognized by 9-1-1 mAb. The competition study with IFN-alpha 88 fragments allowed to locate the epitope recognized by 2-2-1 mAb between amino acid residues 51 and 166. The epitope blocking test indicated that 2-2-1 mAb was directed to an epitope overlapping that of previously reported for mAb NK-2, located around Glu at position 113.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284463 TI - [Formation of a parallel RNA-RNA duplex in vivo in Escherichia coli cells]. PMID- 1284464 TI - Effect of cardiac or heart-lung transplantation on the quality of life of the paediatric patient. AB - Despite the increase in the use of heart and heart-lung transplantation as methods of treatment for children with end stage heart or lung disease, there is little documented research about the psychological implications of such procedures or about the effects of transplantation on quality of life. Twenty eight children were studied before and 3 months after heart or heart-lung transplantation and compared with 28 normal children. Developmental and cognitive function were within the normal range, although performance was at a significantly lower level on a number of parameters compared with the normal group. There were no significant changes in any of the developmental or cognitive parameters after transplantation. Pre-operatively the prevalence of problem behaviour at home was significantly higher in the transplant group compared with the normal group, but there was a significant reduction in the prevalence of problem behaviour following transplantation. Early postoperative findings indicate an improvement in quality of life after heart or heart-lung transplantation but longer term follow-up is now necessary. PMID- 1284465 TI - Assessing the symptoms, anxiety and practical needs of HIV/AIDS patients receiving palliative care. AB - We report the work of two community teams who care for people with AIDS/HIV related illness, the characteristics of patients referred, and the impact of the teams on four aspects of quality of life. Data was collected on 140 patients (85 St. Mary's Home Support Team, 55 Bloomsbury Community Care Team) who were referred to and remained in the care of these teams until death. All patients were male, mean age 37.9 years, 116 were homosexual. Most referrals were from genito-urinary medicine clinics (48%) or AIDS wards (41%). There was a wide range of reasons for referral. At referral 62% were in hospital and 35% at home. Mean time in care was 31 weeks 5 days. Fifty-seven per cent died in hospital, 22% at home and 21% in a hospice. The Support Team Assessment Schedule (STAS), consisting of 17 items of care, was used by the teams to measure aspects of quality of life. Throughout care until death four STAS items: pain control, symptom control, patient anxiety and practical aid are reported in detail. Symptom control was a commonly severe problem at referral and although the teams had some success in improving this item it remained a serious problem throughout care. Patient anxiety, also a commonly severe problem at referral, improved significantly throughout care. Pain control was less commonly severe at referral and improved significantly throughout care. Practical aid, in contrast, was rarely a severe problem at any stage of care. PMID- 1284466 TI - Three novel mutations in the cystic fibrosis gene detected by chemical cleavage: analysis of variant splicing and a nonsense mutation. AB - We have used the chemical cleavage mismatch technique to screen for mutations in the cystic fibrosis gene. Analysis of exons 10 and 11 in the first nucleotide binding fold led to the detection of several described mutations and two novel mutations, V520F and C524X. V520F results from a G-->T nucleotide substitution changing a valine to a phenylalanine residue, while C524X (a nonsense mutation), results from a C-->A transversion. A third novel mutation, Q1291H (G-->C), at the last nucleotide of exon 20, would substitute a histidine residue for glutamine. Further study, involving RNA based PCR, revealed that Q1291H was also a splice mutation. Both correctly and aberrantly spliced mRNAs are produced from the Q1291H allele. The incorrectly spliced product results from the use of a nearby cryptic splice site 29 bases into the adjacent intron. PMID- 1284468 TI - A new missense mutation (R1283M) in exon 20 of the cystic fibrosis transmembrane conductance regulator gene. PMID- 1284467 TI - Isolation of a new gene from the distal short arm of the human X chromosome that escapes X-inactivation. AB - A gene, designated GS1, was identified by its association with a CpG island approximately 100 kb telomeric to the steroid sulfatase (STS) locus on the distal short arm of the human X chromosome. Both cDNA and genomic clones of the GS1 gene have been isolated and characterized. The cDNA clone detects a 2.3 kb transcript in human placenta and fibroblasts, and may encode a protein of 214 amino acid residues. Although sequences homologous to GS1 cDNA are present on chromosomes 1, 20, X, and Y, the functional GS1 gene is on the X chromosome. The GS1 gene appears to be non-essential, as there are no obvious clinical differences between STS deficient patients with point mutations in the STS gene, and patients with a deletion of the STS and GS1 genes. The GS1 gene is expressed from mouse-human cell hybrids containing active or inactive human X chromosomes, indicating that it escapes X inactivation. Characterization of GS1 genomic clones revealed that the gene consists of 4 exons spanning over 105 kb, with its transcriptional direction opposite to that of the STS gene. The isolation and characterization of a new gene which escapes X inactivation from distal Xp is of interest as it adds to our understanding of the structural organization of the human X chromosome and may help in providing clues regarding the mechanism of X-inactivation. PMID- 1284469 TI - Dinucleotide repeat polymorphism for the hexabrachion gene (HXB) on chromosome 9q32-34. PMID- 1284470 TI - Identification and developmental expression of the Xenopus laevis cystic fibrosis transmembrane conductance regulator gene. AB - An amphibian homologue of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene has been isolated from Xenopus laevis by polymerase chain reaction (PCR) amplification. The 4455bp sequence encodes a predicted polypeptide of 1485 amino acids which has an overall homology at the amino acid level of 77% identity and 88% similarity with human CFTR. Comparison of these evolutionarily diverse CFTR sequences has structure-function implications. Investigation of the expression of the Xenopus gene during early stages of development (Stages 1-48), using RNAase protection assays and PCR analysis of total Xenopus RNA, shows CFTR mRNA to be present at the very earliest stages of development, including the oocyte and blastula stages, with increasing amounts during subsequent development. The identification of mRNA for a CFTR homologue in the Xenopus oocyte and early stages of development has implications for its biological role. PMID- 1284471 TI - A nonsense mutation in exon 4 of the cystic fibrosis gene frequent among the population of the Reunion Island. PMID- 1284472 TI - Tetranucleotide repeat polymorphism at the human myelin basic protein gene (MBP). PMID- 1284473 TI - AvaII RFLP of human keratin 10 (KRT-10) detected by PCR. PMID- 1284474 TI - Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome. AB - Laron syndrome is an autosomal recessive condition characterized by resistance to growth hormone. We sought to determine the molecular basis of this condition in an Ecuadorean population with a high incidence of affected individuals. Growth hormone receptor gene sequences from an obligate heterozygote were amplified by the polymerase chain reaction and screened for mutations using denaturing gradient gel electrophoresis. Only exon 6 revealed homo- and heteroduplexes on denaturing gradient gels. Sequencing revealed a substitution of guanine for adenine in the third position of codon 180 that did not change the amino acid encoded. Sequencing of the exon 6-exon 7 splice junction from RNA-polymerase chain reaction amplified cellular RNA of an affected individual revealed that the substitution activates a 5' splice site 24 nucleotides upstream from the normal exon 6-intron 6 boundary. Splicing in two probands' lymphoblasts occurred virtually exclusively at the abnormal 5' splice site created by the codon 180 substitution. Exon 6 sequences from 38 patients and 47 relatives were amplified and analyzed by sequencing or dot-blot hybridization with allele-specific oligonucleotides. The substitution was detected in 74 of 76 Laron syndrome patients' GH-receptor alleles. All 26 parents and 12 of 21 unaffected siblings were heterozygous for this mutation. It was absent in 61 unrelated unaffected control individuals. We conclude that the codon 180 nucleotide substitution probably causes Laron syndrome as translation of the observed, abnormally spliced growth hormone receptor transcript would lead to the synthesis of a receptor protein with an 8 amino acid deletion from the extracellular domain. PMID- 1284475 TI - Lethal perinatal osteogenesis imperfecta due to a type I collagen alpha 2(I) Gly to Arg substitution detected by chemical cleavage of an mRNA:cDNA sequence mismatch. AB - A single base mismatch was detected by a chemical cleavage method in heteroduplexes formed between patient mRNA and a control collagen alpha 2(I) cDNA probe in a case of osteogenesis imperfecta type II. The region of the mRNA mismatch was amplified using the polymerase chain reaction, cloned and sequenced. A heterozygous point mutation of G to C at base pair 1,774 of the collagen alpha 2(I) mRNA resulted in the substitution of glycine with arginine at amino acid position 457 of the helix. Type I collagen of alpha 1(I)- and alpha 2(I)-chains from the patient migrated slowly on electrophoresis due to increased levels of posttranslational modification of lysine. The parents' fibroblast collagen did not contain the mRNA mismatch and the collagens showed normal electrophoretic behaviour. Two-dimensional electrophoresis of the CNBr peptides from the patient's collagen confirmed the excessive posttranslational modification of the alpha 1(I)- and alpha 2(I)-chains in the CNBr peptides N-terminal to the mutation due to disruption of the obligatory Gly-X-Y triplet repeat of the helix. The mutation led to reduced procollagen secretion and helix destabilization as evidenced by a decreased thermal stability. These data lend further support to the accumulating evidence that type I collagen alpha 2(I) glycine substitution mutations result in the same spectrum of clinical severity as those in the alpha 1(I)-chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284476 TI - Complete mutation detection using unlabeled chemical cleavage. AB - We have developed a strategy for the complete detection of point mutations, small insertions and deletions by chemical cleavage based on the methodology of Cotton et al. (1988). The technique was extended by the development of a nonisotopic cleavage product detection system using silver staining after gel electrophoresis. The complete mutation detection was achieved by use of mutant and wild-type DNAs in equimolar quantities in duplex formation, thus any mismatches that are resistant to chemical cleavage (e.g., some T.G mismatches) are easily detected by cleavage of the complementary heteroduplex (e.g., A.C mismatch). With such a strategy mutant DNAs can be screened for mutations and polymorphisms. The advantages of complete unlabeled mutation detection are considerable. PMID- 1284477 TI - Identification of a frameshift mutation (1609delCA) in exon 10 of the CFTR gene in seven Spanish cystic fibrosis patients. PMID- 1284478 TI - Missense variation of the CFTR gene codon 507. PMID- 1284479 TI - Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for response to therapy with partial exchange transfusions. PMID- 1284480 TI - Successful targeting of the mouse cystic fibrosis transmembrane conductance regulator gene in embryonal stem cells. AB - We wish to construct a mouse model for the human inherited disease cystic fibrosis. We describe here the successful targeting in embryonal stem cells of the murine homologue (Cftr) of the cystic fibrosis transmembrane conductance regulator gene, as the first critical step towards this end. The targeting event precisely disrupts exon 10, the site of the major mutation in patients with cystic fibrosis. The targeted cells are pluripotent and competent to form chimaeras. PMID- 1284481 TI - Expression of the whey acidic protein in transgenic pigs impairs mammary development. AB - The whey acidic protein has been found in milk of mice, rats, rabbits and camels, and its gene is expressed specifically in mammary tissue at late pregnancy and throughout lactation. A characteristic of whey acidic protein is the 'four disulfide-core' signature which is also present in proteins involved in organ development. We have generated six lines of transgenic pigs which carry a mouse whey acidic protein transgene and express it at high levels in their mammary glands. Transgenic sows from three lines could not produce sufficient quantities of milk to support normal development of healthy offspring. This phenotype appears to be similar, if not identical, to the milchlos phenotype exhibited by mice expressing whey acidic protein transgenes. Mammary tissue from post-partum milchlos sows had an immature histological appearance, which was distinct from that observed during normal development or involution. Expression of the whey acidic protein transgene was found in mammary tissue from sexually immature pigs from milchlos lines, but not in sows from lines that appeared to lactate normally. We suggest that precocious synthesis of whey acidic protein impairs mammary development and function. Impaired mammary development due to inappropriate timing of whey acidic protein expression is consistent with the notion that proteins with the 'four-disulfide-core' signature participate in tissue formation. PMID- 1284482 TI - Disruption of the cystic fibrosis transmembrane conductance regulator gene in embryonic stem cells by gene targeting. AB - We have successfully disrupted the cftr (cystic fibrosis transmembrane conductance regulator) gene at its endogenous locus in embryonic stem cells by gene targeting. We are using a double replacement strategy to introduce subtle mutations into exon 10. We report here the first step of creating a null mutation by insertion of a functional hprt (hypoxanthine phosphoribosyl transferase) mini gene into exon 10 of the cftr gene. Targeted embryonic stem cell clones were identified by PCR screening and confirmed by Southern blot analysis. One of the cftr targeted clones has been injected into recipient blastocysts and shown to contribute to chimaeras. The targeted clones will now be used as the starting point for a second gene targeting step to remove the hprt gene in exon 10 with the concomitant introduction of the delta F508 mutation or other mutations. PMID- 1284484 TI - [Effect of LDL oxidation on the immunoreactivity of human apolipoprotein B]. PMID- 1284485 TI - [Hepatitis C virus infection in hemodialysis patients]. AB - To study whether HCV infection is present in dialysis patients and the status of antibody responses to HCV viremia, 16 patients undergoing hemodialysis were assayed for anti-HCV by ELISA and RIBA. A high incidence of anti-HCV (13/16) was found. All the 16 patients were studied for HCV viremia by 'nested' PCR and 10 were HCV RNA positive. Altogether 14 were anti-HCV and/or HCV RNA positive, which indicates that the incidence of HCV infection is high in hemodialysis patients, at least in some units. Cloning, sequencing of the PCR products showed high homology among isolates, with 91% homology to that of Japanese strains. It is important to study anti-HCV/HCV RNA in dialysis patients. PMID- 1284483 TI - Expression of human serum albumin in the milk of transgenic mice. AB - We have tested the feasibility of producing large quantities of human serum albumin (HSA) in the milk of transgenic livestock by generating transgenic mice as a model system. The sheep beta-lactoglobulin (BLG) 5'-regulatory promoter sequences were used to support expression of BLG or HSA in transgenic mice. Transgenic animals generated from the entire BLG gene including 3, 5.5 or 10.8 kb of 5'-sequences demonstrated that 3 kb of 5'-sequences were sufficient to support high levels of expression of BLG, and that the longer 5'-sequences did not improve upon the levels of expression. As such, the 3 kb 5'-sequences were used to drive expression of HSA in BLG-HSA constructs. HSA was not detectably expressed in eight transgenic lines generated from a BLG-HSA construct containing the HSA cDNA. Two transgenic lines of 26 generated, using five different constructs, with an HSA minigene possessing the first intron expressed HSA in their milk. One of these expressed HSA at high levels (2.5 mg ml-1) and has stably transmitted this ability to its progeny. A high percentage of transgenic mouse lines (four of six) generated from a vector containing an HSA minigene possessing introns 1 and 2 expressed HSA in their milk at levels which ranged from 1 to 35 micrograms ml-1. In a similar trend, levels of expression of HSA by transfected tissue culture cells from BLG-HSA vectors containing an introduced SV40 enhancer were low with the HSA cDNA, increased with the HSA minigene with intron 1 and increased further with the minigene containing introns 1 and 2. This study demonstrates that high levels of HSA can be expressed in the milk of transgenic animals, that introns of the HSA gene play a role in its expression and that transfected cell lines may be used to quickly evaluate the relative expression efficiencies of various vector constructs intended for future transgenic evaluation. PMID- 1284486 TI - Oxytocin actions on voltage-dependent ionic channels in pregnant rat uterine smooth muscle cells. AB - The effects of oxytocin, a uterotonic polypeptide hormone, on the voltage dependent slow calcium, fast sodium, and potassium channel currents were studied using whole-cell voltage clamp of freshly isolated cells from late pregnant (18 21 day) rat myometrium. The calcium current was rapidly inhibited by oxytocin (about 25% inhibition at 20 nM) in a dose-dependent manner, and this inhibitory effect was completely reversible by washout. However, inhibition was not observed when barium was used as the charge carrier. Sodium current and potassium current were not modified by oxytocin, thus sodium and potassium currents may not play important roles in oxytocin-induced augmentation of uterine contraction. It is concluded that oxytocin stimulates uterine contraction by mechanisms other than augmentation of the voltage-dependent calcium current, e.g., by release of Ca from sarcoplasmic reticulum (by inositol triphosphate) or by activation of a receptor-operated Ca channel. The inhibition of the slow calcium current may be induced by the elevation of [Ca]i. PMID- 1284487 TI - [Effect of combined therapy with selective beta 1- and alpha 1-adrenergic agonists upon postprandial hypotension in patients with progressive autonomic failure]. AB - Food ingestion increases mesenteric blood flow, and then results in a decrease of total vascular resistance (VR). Postprandial hypotension (PPH) may be caused by a lack of compensatory increase in cardiac output (CO) together with a lack of reflex peripheral vasoconstriction to the decrease in total VR. In order to increase CO and VR, we orally administered both denopamine 10 mg (a selective beta 1-adrenergic agonist) and midodrine HCl 4 mg (a selective alpha 1-adrenergic agonist) to six patients with progressive autonomic failure (AF). PPH was well prevented by concomitant administration of both denopamine and midodrine HCl 30 min before oral ingestion of 75 g of glucose, i.e., CO and portal blood flow as well as VR in the lower legs increased. These hemodynamic reactions after oral ingestion of 75 g of glucose were very similar to those in the control subjects. The marked increase in heart rate after drug administration may be the result of cardiac supersensitivity in patients with AF. Combined oral administration of both denopamine and midodrine HCl is a safe and useful management of PPH in patients with AF. PMID- 1284489 TI - Inhibitory effects of insulin-like growth factor-binding proteins on steroidogenesis by human granulosa cells in culture. AB - The effects of insulin-like growth factor-binding proteins (IGFBPs) 1 and 3 on steroidogenesis by human granulosa cells has been examined. Both IGFBP-1 and IGFBP-3 produced a dose-related inhibition of IGF-I-stimulated oestradiol accumulation in granulosa cell-conditioned medium with complete reversal of the effects of IGF-I in the presence of a molar excess of binding protein. IGFBPs 1 and 3 also exerted a small (25-40%) but significant and consistent inhibition of oestradiol secretion in response to follicle-stimulating hormone (FSH) alone. The progesterone response to IGF-I was inhibited by IGFBPs 1 and 3 but there was no effect on FSH-stimulated progesterone production. These data support the concept of a physiologically important intraovarian IGF system in the human ovary and demonstrate an unequivocally inhibitory effect of IGFBPs 1 and 3 on IGF-I stimulated granulosa cell steroidogenesis. PMID- 1284488 TI - Retinotopic order is surprisingly good within cell columns in the cat's lateral suprasylvian cortex. AB - The retinotopic map in the striate-recipient region of the cat's lateral suprasylvian cortex (referred to here as the lateral suprasylvian area (LS)) has generally been described as quite disorderly. The disorder is commonly attributed to receptive field scatter within cell columns, reflecting the very large size of receptive fields. However, scatter within columns has never been investigated. In the experiments reported here, we examined the receptive field scatter of cells in columns, and also the scatter of a limited sample of their afferents arising from areas 17 and 18. To measure post-synaptic receptive field scatter, electrode penetrations were made parallel to columns in LS, with the electrode approaching from the medial side, traversing the suprasylvian gyrus and emerging into the suprasylvian sulcus. In all 13 such penetrations, receptive fields were clustered together despite their large size. Their centers were scattered over a region that occupied on average less than 20% of the largest field in the column. In contrast, in columns in areas 17 and 18 receptive field centers reportedly are dispersed over regions about equal to the largest of the fields (Hubel and Wiesel 1962, 1965, 1974). The scatter of afferents' receptive fields was assessed anatomically by measuring the overlap between patches of different anterograde tracers in LS. These patches represented terminal labeling from two adjacent or overlapping tracer injections in area 17. While a large degree of overlap would be predicted if afferents have substantial scatter, we found the overlap to be small unless the two injection sites themselves were highly overlapping. Scatter in afferents' receptive fields was measured more directly by physiological recording. In previous experiments, cells in LS were silenced by the local injection of kainic acid, and responses were recorded from axon terminals arising from areas 17 and 18 (Sherk 1989). We examined the receptive field scatter in three penetrations made approximately normal to the cortical surface. Scatter was modest, much less than predicted by the size of post-synaptic receptive fields. Because the degree of receptive field scatter for postsynaptic cells in LS was similar to that of inputs from areas 17 and 18, the scatter of these inputs might be entirely responsible for that seen postsynaptically. Postsynaptic receptive field scatter, on the other hand, was too small to explain the reported disorder in the map in LS. PMID- 1284490 TI - Rat Sertoli cell clusterin, alpha 2-macroglobulin, and testins: biosynthesis and differential regulation by germ cells. AB - Clusterin, alpha 2-macroglobulin and testins are three novel Sertoli cell proteins whose physiological functions may be related to cell-cell interactions in the seminiferous epithelium of the testis. We have demonstrated the biosynthesis of clusterin, alpha 2-macroglobulin, and testins by Sertoli cells in vitro using pulse-chase labeling analysis. For clusterin, two precursors with an apparent molecular weight (M(r)) of 72,000 (PH) and 66,000 (PL) were detected in the Sertoli cell cytosol in addition to the alpha (M(r) 43,000) and beta (M(r) 35,000) subunits of the mature protein. However, the precursors were not secreted into the medium since only the alpha and beta subunits of clusterin were detected. For alpha 2-macroglobulin and testins, no precursor molecules were detected either in the Sertoli cell cytosol or culture medium. The polarized secretory pattern of these proteins and their regulation by follicle stimulating hormone (FSH) and testosterone (T) were examined using a bicameral culture chamber that mimics the in vivo physiological conditions. Clusterin was secreted almost exclusively into the apical chamber of the bicameral culture unit with an apical:basal ratio of 30:1. In contrast, alpha 2-macroglobulin and testins had an apical:basal ratio of 1:1 and 1.5:1, respectively. Thus, the polarized secretory pattern for clusterin is different from alpha 2-macroglobulin and testins. It was noted that FSH and T, the known Sertoli cell regulators, did not affect the secretion of either clusterin or alpha 2-macroglobulin. Due to the morphological intimacy between Sertoli cells and germ cells in the adluminal compartment of the testis, the effects of germ cell-conditioned medium were investigated. Addition of germ cell-conditioned medium (1-30 micrograms protein) to the apical chamber of the bicameral culture unit caused a dose-dependent inhibition of clusterin and testins apical secretion and a slight but statistically significant stimulation of their basal secretion. In contrast, the secretion of alpha 2-macroglobulin by Sertoli cells was stimulated both apically and basally. These observations suggest that germ cell-conditioned medium contains a biological factor(s) that differentially regulates the bidirectional secretion of Sertoli cell proteins. These studies therefore reveal the complicated regulatory processes involved in cell-cell interactions in the seminiferous epithelium. PMID- 1284491 TI - Atrial natriuretic peptide effects in AtT-20 pituitary tumour cells. AB - Whether atrial natriuretic peptide (ANP)-evoked inhibition of corticotrophin releasing factor (CRF)-stimulated ACTH secretion was also manifest in ACTH secreting AtT-20 pituitary tumour cells was investigated. ANP stimulated increases in cGMP accumulation at concentrations of the peptide above 10(-8) M which indicates the presence of the ANP receptors on these cells. CRF stimulated a concentration-dependent increase in ACTH secretion from AtT-20 cells which was unaffected by ANP, 8-bromo-cGMP, or sodium nitroprusside (SNP). Calcium stimulated a concentration-dependent increase in ACTH secretion from electrically permeabilised cells which was unaffected by co-incubation with cGMP but potentiated by cAMP. These results reveal the presence of ANP receptors on AtT-20 cells but suggest that an incomplete expression of the stimulus-secretion coupling mechanisms for ANP, at some point after cGMP production, prevents the effects of natriuretic peptides upon ACTH secretion being manifest in these cells. PMID- 1284492 TI - Steroidogenesis-inducing protein interacts with transforming growth factor-beta to stimulate DNA synthesis in rat granulosa cells. AB - We have examined the effects of steroidogenesis-inducing protein (SIP), previously isolated from human follicular fluid, on the synthesis of DNA by granulosa cells isolated from diethylstilbestrol-primed immature rats. SIP alone had no effect but in conjunction with transforming growth factor-beta (TGF-beta) there was an increase in [3H]thymidine incorporation into granulosa cell DNA. The increase in [3H]thymidine into DNA was due to an increase in the number of labeled granulosa cells as assessed by autoradiography. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) interfered with the ability of SIP and TGF-beta to promote DNA synthesis. Previously, we reported that the growth-promoting action of follicle-stimulating hormone (FSH) on rat granulosa cells in vitro was dependent on TGF-beta, and EGF inhibited the actions of FSH plus TGF-beta on [3H]thymidine incorporation into DNA. Since the dependency of SIP on its interactions with TGF-beta and the ability of EGF to interfere with the process were similar to the properties reported for FSH, this raised the possibility that the actions of SIP were mediated through the accumulation of intracellular cAMP. However, when the hypothesis was tested, SIP had no effect on cAMP levels in the presence or absence of TGF-beta, under conditions in which FSH stimulated cAMP accumulation. In conclusion, DNA synthesis in rat granulosa cells is dependent on the presence of TGF-beta. In the presence of TGF-beta, FSH or SIP, acting through cAMP-dependent and cAMP independent mechanisms respectively, can recruit more cells to enter the cell cycle and initiate DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284493 TI - Nitric oxide as a signal in thyroid. AB - It is now well established that agonist activation of the PIP2/calcium cascade in the thyroid results in the enhancement of cGMP accumulation presumably by activation of the soluble guanylate cyclase. In many tissues the physiological signal controlling soluble guanylate cyclase is nitric oxide (NO) and its synthesis from arginine is controlled by the intracellular Ca2+. In this report we show results that suggest that NO may be the intermediate of the cGMP response to the activation of the PIP2/calcium cascade. In dog thyroid slices, incubation with carbamylcholine or A23187 increases significantly free intracellular Ca2+ levels and the cGMP content of the slices. NG-Monomethyl-L-arginine (NMMA), a competitive inhibitor of arginine for nitric oxide synthase, inhibited these cGMP responses but not the action of sodium nitroprusside which activates soluble guanylate cyclase directly. The inhibition was relieved by arginine. Methylene blue, which blocks the activation of soluble guanylate cyclase by NO, also decreased the three stimulatory effects. NMMA and methylene blue also decreased the basal levels of cGMP. NO may therefore be an important autocrine and paracrine factor in thyroid. PMID- 1284494 TI - Are ionic fluxes of pancreatic beta cells a target for gastric inhibitory polypeptide? AB - Gastric inhibitory polypeptide (GIP), an incretin candidate, is suggested to amplify the glucose-induced insulin secretion. To evaluate its mode of action we examined whether GIP affects 86Rb+ efflux, 45Ca2+ uptake or efflux, and intracellularly recorded electrical activity of mouse pancreatic islets. GIP (5 nM) neither inhibited 86Rb+ efflux at 3 mM glucose nor modulated 86Rb+ efflux that was inhibited by 5.6 mM glucose or stimulated by the calcium ionophore A23187. 45Ca2+ uptake was increased by GIP in the presence of 16.7 mM which was not observed at 3 or 11 mM glucose. GIP elevated 45Ca2+ efflux from islets, but did not modify 45Ca2+ efflux when a virtually Ca2+ free medium was used. Electrical activity of beta cells induced by 16.7 mM glucose was significantly increased by 5 nM GIP. It is concluded that the amplification of insulin release by GIP is based on the effect of GIP on Ca2+ uptake. PMID- 1284495 TI - Characterization of insulin-like growth factor binding proteins secreted by cultured bovine theca and granulosa cells. AB - Insulin-like growth factor binding proteins (IGFBPs) secreted by bovine granulosa and theca interna cells cultured in the presence of different luteinizing factors -insulin (2 micrograms/ml), forskolin (10 microM), or a combination of the two were examined and characterized. Direct binding of [125I]IGF to the conditioned media was compared to progesterone production under these different treatments. In theca cells, maximal secretion of IGFBPs was achieved using forskolin alone, whereas maximal progesterone production was induced by the insulin+forskolin treatment. In contrast, maximal secretion of both IGFBPs and progesterone in granulosa cells was achieved using forskolin alone. IGFBP species secreted by the two cell types under the different treatments were detected by ligand blotting. Conditioned media from theca cells in serum-free medium collected on the seventh day of culture exhibited three bands of 34, 40 and 44 kDa when treated with insulin or forskolin. The intensity of the 40-44 kDa complex was enhanced and a 21 kDa band appeared when cells were treated with a combination of insulin plus forskolin. Conditioned media of granulosa cells stimulated with insulin or forskolin exhibited 21, 27, 29, 34 and 40-44 kDa bands. Treatment with insulin+forskolin greatly increased the intensity of a 40-44 kDa complex. A similar shift towards high molecular weight binding proteins was observed when these media were analyzed by high-performance liquid chromatography gel filtration. These findings substantiate the secretion of IGFBPs by bovine theca and granulosa cells and show it to be dependent on culture treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284497 TI - Early neurochemical changes in the autonomic neuropathy of the gut in experimental diabetes. AB - Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes. PMID- 1284496 TI - Stimulation of testosterone production by atrial natriuretic peptide in isolated mouse Leydig cells results from a promiscuous activation of cyclic AMP-dependent protein kinase by cyclic GMP. AB - The aim of this study was to examine the possibility that atrial natriuretic peptide-stimulated testosterone production by mouse Leydig cells results from an activation of cAMP-dependent protein kinase (kinase A) by cGMP. In these cells, both 8Br-cGMP and 8Br-cAMP could stimulate testosterone production, though the latter was approximately 50-fold more potent. Following the stimulation of the cells with the atrial peptide, a dose-related decrease in the cellular protein bound cAMP accompanied by a concomitant increase in the protein-bound cGMP was observed. The steroidogenesis stimulated by both human chorionic gonadotrophin (hCG) and atrial peptide was inhibited in a dose-dependent manner by a cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate, Rp-isomer (RpcAMPS). In a cell-free [3H]cAMP binding assay, we have shown that unlabelled cGMP and RpcAMPS could competitively inhibit the [3H]cAMP binding, confirming that cAMP, RpcAMPS and cGMP could bind to the same binding protein. Finally, in a cell-free kinase A assay system, we have demonstrated that in lysates prepared from either atrial peptide or hCG-stimulated cells, the cellular kinase A was activated to an equal extent. We conclude from the data obtained that cGMP can bind to the cAMP-binding sites of kinase A and thereby brings about a promiscuous activation of this kinase. This appears to be an underlying mechanism by which atrial peptide hormone is able to stimulate the steroidogenesis in mouse Leydig cells. PMID- 1284498 TI - Peptide alterations in autonomic diabetic neuropathy prevented by acetyl-L carnitine. AB - Autonomic neuropathy and gastrointestinal problems are among the most common complications of diabetes. In this report it is shown that a possible correlation between the two disorders might exist, since diabetes causes a profound alteration of the peptidergic innervation of the gut. It is reported that 14 weeks after diabetes induction with alloxan the levels of substance P and methionine-enkephalin are markedly reduced throughout the intestine, while vasoactive intestinal polypeptide content is dramatically increased. Therefore the enteric innervation of diabetic animals is completely disorganized, with some systems undergoing atrophy and others undergoing hypertrophy. Treatment of diabetic animals with acetyl-L-carnitine prevents the onset of the marked peptide changes described above. The results suggest a potential for acetyl-L-carnitine in the treatment of autonomic neuropathies. PMID- 1284499 TI - Acetyl-L-carnitine prevents substance P loss in the sciatic nerve and lumbar spinal cord of diabetic animals. AB - Diabetic neuropathy is a disease of peripheral nerves, characterized by axonal atrophy and degeneration that might be preceded by a marked impairment of axonal transport and by a reduced conduction velocity. Sensory nerves are particularly susceptible to diabetes. In the present report it is shown that experimental diabetes in rats causes a significant reduction of the content of the pain related neuropeptide substance P in sciatic nerve and lumbar spinal cord. Such a loss of substance P is fully prevented by acetyl-L-carnitine treatment. The neuroprotective pharmacological effect is selective and takes place without significant changes of hyperglycaemia and without modifications of the reduced rate of body growth typical of diabetic animals. PMID- 1284500 TI - Intraspinal degenerative atrophy caused by sciatic nerve lesions prevented by acetyl-L-carnitine. AB - Peripheral nerve lesions cause retrograde changes in the spinal cord, involving initially the descending serotoninergic pathways and later the substance P sensory input and methionine-enkephalin interneurons. Within 48 h after sciatic nerve resection there is a significant increase of 5-hydroxyindoleacetic acid in the lumbar spinal cord with no changes of serotonin metabolism in the cell body areas. The immunocytochemical analysis of the spinal cord shows that 20 days after nerve lesion there is a loss of substance P-positive boutons in the laminae I and II of the dorsal horn in the lumbar segment. Such a morphological change is correlated by radioimmunoassay for substance P and methionine-enkephalin, that reveals a significant loss of both peptides. Treatment with acetyl-L-carnitine prevents the early 5-hydroxyindoleacetic acid increase and the reduction of peptide content observed 20 days after lesioning the sciatic nerve. These data suggest that treatment with acetyl-L-carnitine exerts a neuroprotective activity preventing the retrograde changes triggered by peripheral nerve lesions. PMID- 1284502 TI - [The efficiency of surgical treatment of patients with malignant tumors of nasal cavity and paranasal sinuses]. AB - In the years 1966-80, 96 patients with malignant tumors of nasal cavity and paranasal sinuses were surgically treated in the Department of Otolaryngology, Medical University in Cracow. Out of 29 patients with macro and microscopic radical surgical treatment, 11 (37.9%) survived 5 years. The remained 62 patients, considering non-radical surgical treatment, have been additionally treated by full course of irradiation. Out of this group 34 (54.8%) survived 5 years. These data suggest that indications for additional irradiation should be extended. PMID- 1284501 TI - [Immunotherapy of brain tumors]. PMID- 1284503 TI - Renal carcinoma (RC): regulation of antitumoral immune responses. AB - Advanced renal cell carcinoma (RCC) is almost completely resistant to conventional therapeutic approaches such as chemotherapy or radiotherapy. There is growing evidence that few patients may be cured from metastatic RCC by immunotherapy. Unlike 20 years ago, current immunotherapeutic regimens are set up with pure drugs, such as recombinant cytokines. Immunotherapy interferes with a complicated network of cellular immune effectors, e.g., T-lymphocytes, macrophages and natural killer cells. The activity of immune effectors cells is regulated and fine-tuned by a variety of cytokines, e.g., interleukins and interferons which are produced predominantly by the immune effector cells themselves. It is reasonable to expect that in the near future more patients will benefit from immunotherapy for RCC as the knowledge on regulation of the immune response to tumors is rapidly increasing. PMID- 1284504 TI - Mycobacterial adherence and BCG treatment of superficial bladder cancer. AB - The importance of adherence of BCG (Bacillus Calmette Guerin) to the bladder wall as an initiator of the processes leading to the BCG-induced antitumor activity is still controversial. A study was initiated addressing this subject by an experimental procedure modulating BCG adherence using pretreatment with pentosan polysulphate (PPS), a polysulphated polysaccharide with glycosaminoglycan (GAG) like properties and reported bacterial antiadherence properties to the bladder mucosa. Furthermore, PPS is applied as a drug to treat chronic and radiation induced cystitis. It was reasoned that application of PPS during BCG treatment may prevent cystitis, a common side effect. However, nothing is known about a potential interaction of PPS with the effectiveness of BCG treatment. The results obtained with guinea pigs receiving prior to each of the 6 weekly instillation with BCG-RIVM (1 x E7 cfu) an intravesical pretreatment with 10 mg PPS in 1 ml for 0.5 hours indicated an enhancement of the PPD skin reaction, inflammatory response and number of iliac lymph nodes cells after instillation 6 compared to non-pretreated animals. These results, contrary to the expected, were supported by the indication of an increased binding of [3H]uracil-labeled BCG to the bladder after PPS pretreatment. To explain these results, the binding of PPS to the bladder wall and BCG were quantitated spectrophotometrically with DMB (dimethylmethylene blue). After administration of 40 g, 80 g, and 10 mg in appropriate volumes into the rat, guinea pig & human bladder 0.9 +/- 0.3, 4.3 +/- 1.1g, and 5.7 +/- 1.8 mg PPS (n > 5) were recovered respectively, showing a strong adherence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284505 TI - Retrograde factors in peripheral nerves. AB - The relationship between the neuron and its target is explored and the possible mechanisms for achieving correct connections are analysed. The most plausible mechanism is the presence of a retrograde intra-axonal message from the target to the neuronal cell body. The molecular form of the message and the mechanisms to achieve this signal transduction are discussed and it is proposed that there are two types of neurotrophic factors. One has a short-acting second messenger, itself incapable of surviving for the time required for transport to the cell body and thus requiring the transport of the message-generating complex to the cell body. The other has a long-lasting second messenger complex which is well able to survive the transport to the cell body so that there is no need for the transport of the neurotrophic factor itself. Thus all neurotrophic factors do not themselves require retrograde axonal transport and such non-transportable factors may generate intricate messages due to associations of signal transduction molecules via binding sites such as phosphorylated tyrosines and the src homology domain 2. PMID- 1284506 TI - [Projections from lamina V of the cerebral cortex to the dorsomedial thalamic nucleus and neighboring nuclei]. AB - The laminar projections from the cerebral cortex to the mediodorsal thalamic nucleus and adjacent thalamic nuclei were studied by means of the horseradish peroxidase (HRP) retrograde axonal transport method. A possible correlation was found between the connectivity arising from layer V of the cerebral cortex, and the rich-acetylcholinesterase (AChE) regions within the subcortical structures under study. This suggests the possibility that layer V of the cerebral cortex in Alzheimer's disease is initially affected and subsequently those rich-AChE subcortical regions with which it is connected. PMID- 1284507 TI - [Biochemical and immunochemical analyses of the protein components of the cell wall in group-A streptococci isolated by a sparing chemical method]. AB - To study the protein components of the cell wall of group A streptococci, type M 29, a special preparative method was developed (extraction with 1 M hydroxylamine solution, pH 6.0, and subsequent purification). Altogether six protein fractions were obtained. The isolated proteins were found to be a heterogeneous group of molecules, consisting of 25-40 individual proteins with molecular weights ranging between 13 and 94 kD. The study of the protein fractions thus obtained in the immunodiffusion test with rabbit antiserum to the initial protein preparation revealed that these proteins contained type-specific components, 3-6 type nonspecific protein antigens common with protein antigens of M 1 and M 12, as well as one protein antigen common with type M 1. Fc receptor was shown to be absent. The detected type-nonspecific protein antigens were partially separated by ion-exchange chromatography and some of them could be purified from the admixtures of nucleic acids and group-specific polysaccharide. PMID- 1284508 TI - [Advances in AIDS vaccines]. PMID- 1284509 TI - [Stewart-Treves syndrome. Treatment with bleomycin]. PMID- 1284510 TI - DNA synthesis of plasmids in Escherichia coli. PMID- 1284511 TI - Gel electrophoresis and the structure of RNA molecules. PMID- 1284512 TI - Introductory epidemiological remarks on the EURODIAB program. PMID- 1284513 TI - The HLA system and insulin dependent diabetes: recent findings and prospects for disease prediction. AB - Our knowledge of the genetics of insulin dependent diabetes (IDDM), and in particular the HLA system, has gained considerable expansion thanks to the application of molecular biology. The genetic susceptibility to the disease is linked to the HLA region, particularly at DQ-alpha and DQ-beta chain genes. Particular amino acid other than aspartic acid in position 57 of the DQ beta chain and the presence of an arginine in position 52 of the DQ alpha chain and to how these markers can be used to identify subjects at risk for developing IDDM. The identification of such subjects may be useful for the development of strategies aimed to prevent the disease and in addition may offer a new insight into population screening. PMID- 1284514 TI - Natural history and prediction of type 1 diabetes. PMID- 1284515 TI - Immunointervention in insulin dependent diabetes: implications for the epidemiology of the disease. PMID- 1284516 TI - EURODIAB project 1989: registry for type 1 diabetes mellitus in Lombardy. PMID- 1284517 TI - The EURODIAB experience in Lazio. PMID- 1284518 TI - High incidence of type 1 diabetes in Sardinia. Gruppo Collaborativo per l'Epidemiologia dell'IDDM in Sardegna. PMID- 1284519 TI - Role of toxic ingredients in silicone oils in the induction of increased corneal endothelial permeability. AB - Silicone oils may induce pathological changes in corneas or retinas by unknown mechanisms but the effects are probably related to certain specific components. Low molecular weight compounds have been implicated in the induction of toxic tissue reactions. Several of these components, that occur as contaminants or by products in crude silicone oils, were tested for their ability to alter corneal endothelial permeability. In vitro inulin/dextran permeability was measured after one week of in vivo exposure to a non-toxic oil to which various low molecular weight components were added. At least 75% of the anterior chamber volume was replaced with oil +/- additives. A long-chain silanol-terminated polydimethylsiloxane (1000 cps) at 2 mg/ml, tetramethyl-ammonium siloxanolate (a catalyst) at 1 mg/ml and a mixture of a series of linear compounds (MM through MD10M) each at 10 mg/ml all caused a large corneal endothelial permeability increase. A mixture of two short-chain silanol-terminated compounds was less damaging, as was a mixture of a cyclic series. Evidently certain compounds can induce toxic effects on the corneal endothelium whereas other compounds are much less toxic. The linear series and the catalyst, that induce corneal endothelial changes, have been shown to occur in silicone oils. PMID- 1284520 TI - Induction of experimental proliferative vitreoretinopathy in the rabbit eye by intravitreal injections of fibroblast growth factor. PMID- 1284521 TI - Effects of Gingko biloba extracts in a model of tractional retinal detachment. PMID- 1284523 TI - Drug-exposed infants and children: living with a lethal legacy. PMID- 1284522 TI - [The role of polyene fatty acids in the development of acute inflammation in rats]. AB - The effect of n6 and n3 polyunsaturated fatty acids (PUFA) on development of acute inflammation in rats has been studied. During 4 weeks male Wistar rats (initial weight 140-150 g) were on feed containing as lipid component 6% butter and 3% fish oil obtained from Sardinops sagax melanosticta (n3 PUFA-diet). The development of paw oedema induced by subplantar injection of dextran or carrageenan inhibited when the animals were on diet where prevailed n3 PUFA. In contrast, the state of paw oedema, caused by intraperitoneal administration of egg white was similarly high in rats given both n6 and n3 PUFA. PMID- 1284524 TI - Determining the need for speech-language intervention services for infants and toddlers. PMID- 1284525 TI - Genetics in disorders of language. AB - As is typical in science, early work in an area is bound to have weaknesses. Therefore, it is not unexpected that the extent to which conclusions can be drawn from the current research on the genetics of DLD is limited. These limitations stem from the use of heterogeneous samples, the use of overly broad phenotypes, survey rather than objective test data, and only a few studies looking beyond simple familiarity. Future research is in progress that attempts to correct for these weaknesses. Still, some practically useful information can be gleaned from the work done thus far. First, we can now hypothesize something about the pathway from gene to DLD phenotype. Much of DLD, like RD, may be a manifestation of early genetic effects on the structural development of the brain (e.g., Plante, Swisher, and Vance, 1991; Plante, 1991; Molfese and Betz, 1988). However, consequences of these genetic effects for language development can still be modified by environmental events (e.g., treatment). Furthermore, genetic effects do not act in isolation and they are not necessarily static. A number of genetic and non-genetic events in the course of development may positively or negatively modify the disorder (e.g., Tomblin, 1989, Tallal et al., 1991; Molfese and Holcomb, 1989). A related point is that there is evidence for genetic heterogeneity in DLD. That different modes of transmission have been put forth by different authors, suggests that a variety of genetic forms of DLD may exist. This idea is further supported by noting that DLD is a common outcome of a number of clinical syndromes having very different genetic bases (e.g., Williams syndrome, Down syndrome, fragile X, etc.; Siegel-Sadewitz and Shprintzen, 1982; Bellugi et al., 1991). This does not rule out the possibility that a majority of nonsyndromic DLD is due to one or a few major genes, however. Finally, there is also evidence for behavioral heterogeneity in DLD. The data suggest that the genes for DLD are variably expressed. For example, in families selected through a DLD proband, a number of different language-related problems have been noted. Furthermore, when a globally defined DLD individual is examined closely, it is common to find a collection of symptoms, sometimes spanning all the major domains of language (Weiss and Lillywhite, 1981). Overall, the data and concepts presented in this article suggest that the clinician should take careful family histories of clients and, when doing so, attempt to ascertain the specific symptoms that family members other than the client exhibit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284526 TI - Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines. AB - Human and rat cDNAs to Clara Cell 10 kDa protein (CC10) have been previously isolated. Comparison of the amino acid sequences showed that CC10 is homologous to rabbit uteroglobin. Here we present further evidence that human CC10 is the human counterpart of rabbit uteroglobin. We have isolated the gene and have mapped its genomic localization to chromosome 11q11-qter. Sequence analysis of the 5'-flanking region reveals that the homology between the human and the rabbit gene starts at the first exon/intron boundary and extends up to -1.4 kb. A second region of 0.74 kb from -1.77 to -2.51 kb in the human 5'-flanking gene region is homologous to rabbit sequences that include four progesterone receptor binding sites which have been implicated in progesterone regulation of rabbit uteroglobin gene expression in endometrium. Sequence alignment of this region on the nucleotide level shows that only two weak progesterone receptor binding sites are partially conserved. In addition, close inspection of the human and rabbit promoters reveals that the estrogen responsive element and two recently identified cis elements of the rabbit promoter located between -177 and -258 bp are also absent in the human uteroglobin promoter. Despite these differences in the 5'-flanking regions of the genes, we report that the human uteroglobin mRNA is expressed in a human cell line of endometrial origin indicating that human uteroglobin is expressed in the uterus like its rabbit homologue. Thus, it appears that human uteroglobin is not only a marker for lung Clara cells but also an endometrial differentiation marker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284528 TI - Identification of genes using oligonucleotides corresponding to splice site consensus sequences. AB - The identification of genes in genomic DNA presents challenging technical difficulties. We show here the feasibility of using short oligonucleotides based on the consensus sequences surrounding intron-exon junctions to detect random phage and cosmid clones containing genes both through the analysis of DNA blots and by direct screening. Three degenerate oligonucleotides, a 10-mer corresponding to the 5' splice junction and a 9-mer and a 15-mer corresponding to the 3' splice junction, were tested on the known intron-exon boundaries of the cloned human proteolipid protein (PLP) gene at hybridization and washing temperatures appropriate to their length and composition. All predicted hybridizations were observed. The oligonucleotides were also used to identify random genomic plasmid and cosmid clones containing putative intron-exon junctions; the presence of genes in these clones was supported by RNA blot analysis and by cross-hybridization to DNA from other species. This technique should facilitate the identification of genes for inherited diseases by positional cloning studies and will assist in the identification of genes in random clones for the human genome project. PMID- 1284527 TI - Characterization of the human HOX 7 cDNA and identification of polymorphic markers. AB - cDNA clones for a human HOX 7 gene obtained with homologous clones of Drosophila were used in human gene mapping studies. The human cDNA clone was isolated from a library constructed from human embryonic craniofacial material. The sequence of the cDNA demonstrates significant homology with mouse HOX 7. A search for RFLPs identified MboII and BstEII variants. A CA dinucleotide repeat with 5 alleles was also identified and allowed placement of HOX 7 into a defined linkage map. Evidence for linkage disequilibrium was found with markers tested. These results place the human HOX 7 gene in a defined position on 4p. PMID- 1284529 TI - Detection of novel and rare mutations in exon 4 of the cystic fibrosis gene by SSCP. PMID- 1284530 TI - A serine to proline substitution (S1255P) in the second nucleotide binding fold of the cystic fibrosis gene. PMID- 1284531 TI - G27X: a novel mutation in exon 2 of the CF gene. PMID- 1284532 TI - EcoRV RFLP of the desmin (DES) gene and MspI RFLP of the villin (VIL1) gene on human chromosome 2. PMID- 1284533 TI - Alu polymorphism in the human type I Keratin (KRT14) gene. PMID- 1284534 TI - Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium. AB - Cystic fibrosis is the most common autosomal disorder in the Caucasian population. Since the description of the major mutation of this disease in 1989, over 150 of additional mutations have been identified in the CFTR gene. This update summarizes the different mutations identified and reported before March 15 by members of the international Cystic Fibrosis Genetic Analysis Consortium. The report includes information on DNA sequence variations found in the gene. PMID- 1284535 TI - A cystic fibrosis allele encoding missense mutations in both nucleotide binding folds of the cystic fibrosis transmembrane conductance regulator. AB - German cystic fibrosis (CF) chromosomes were screened for molecular lesions in exon 20 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by chemical cleavage of mismatch. An 3884G-to-A transition was detected in two patients which leads to an exchange of a serine by an asparagine in the Walker motif A of the second nucleotide binding fold. The affected serine residue is evolutionarily strongly conserved among the pro- and eukaryotic members of the protein superfamily of traffic ATPases. The two S1251N alleles were linked to the benign missense mutation F508C which is located in another conserved region of CFTR, the center region of the first nucleotide binding fold. Both patients with the complex allele F508C-S1251N are carrying delta F508 on the other CF chromosome and are suffering from severe pulmonary and gastrointestinal CF disease. Although F508C has been classified as a neutral sequence variation because of its discovery in healthy delta F508 gene carriers, it may nevertheless influence CFTR dysfunction caused by the S1251N mutation. PMID- 1284537 TI - Screening for cystic fibrosis mutations in southern France: identification of a frameshift mutation and two missense variations. AB - In the search for mutations in the cystic fibrosis gene in patients from the Mediterranean area, we have analysed exons 4, 9, 10, 19, and 21 by the single strand conformation polymorphism (SSCP) technique in 50 patients with at least one non-delta F508 chromosome. Ten samples demonstrated a shifted band, four in exon 19 and six in exon 21. Sequencing of the PCR fragments has led to the identification of three new sequence alterations, two in exon 19 (3737 delA and I1234V), and one in exon 21 (N1303H). We also analysed the frequency of two known intronic polymorphisms in front of exon 19 (C to A change at nucleotide 3601-65) and exon 21 (G to A change at position 4006-200). PMID- 1284536 TI - A sequence variation in intron 17B of the cystic fibrosis transmembrane conductance regulator gene. PMID- 1284538 TI - Four new mutations of the CFTR gene (541delC, R347H, R352Q, E585X) detected by DGGE analysis in Italian CF patients, associated with different clinical phenotypes. AB - The delta 508 mutation accounts for about 53% of the molecular defects causing cystic fibrosis (CF) in Italy. The numerous additional mutations detected so far are all relatively rare, and about 30% of CF chromosomes carries unknown mutations in our patients. In order to identify the non-delta F508 mutations causing CF in our population, we performed GC-clamped denaturing gradient gel electrophoresis (DGGE) on 9 exons of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a sample of 86 Italian CF patients carrying unknown mutations on at least one chromosome. Direct sequencing of 17 samples showing an altered electrophoretic mobility allowed the identification of four new mutations (541delC, R347H, R352Q, and E585X), five mutations already known (G85E, I148T, G178R, 1078delT, and R347P), and one rare variant (1898 + 3A-->G). The strategy based on GC-clamped DGGE represents an efficient and rapid approach for mutation detection for those genetic diseases, such as CF, in which a large number of rare molecular defects has been described. PMID- 1284539 TI - Cystic fibrosis patients with mutation 1949del84 in exon 13 of the CFTR gene have a similar clinical severity as delta F508 homozygotes. AB - The majority of the identified cystic fibrosis (CF) mutations are very uncommon in the total patient population, making the correlation between the clinical presentation and the molecular alterations difficult. The largest deletion that has been described so far in CF is of 84 bp in exon 13, which corresponds to the regulatory (R) domain of the CF transmembrane conductance regulator (CFTR) protein. We have analysed 340 Spanish CF patients for this deletion, named 1949del84, and found three further compound heterozygous patients for mutations 1949del84 and delta F508, and one for 1949del84 and an unknown mutation. Evaluation of the clinical data in these patients suggests that this in-frame deletion, when associated with delta F508, has a similar disease severity to that of delta F508 homozygous patients. PMID- 1284540 TI - Characterization of an intron 12 splice donor mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. AB - Cystic fibrosis, the most common lethal genetic disease in the white population, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Analysis of DNA from a pancreatic insufficient patient by chemical mismatch cleavage and subsequent DNA sequencing led to the identification of a potential splice mutation in the CFTR gene. A transition of the invariant guanosine to adenosine (1898 + 1G > A) was found at the splice donor site of intron 12. To determine the effect of this mutation on the patient's CFTR transcripts, RNA from the nasal epithelium was reverse transcribed and amplified by the polymerase chain reaction (RT-PCR). Direct sequencing of the PCR products revealed that the transcript from the chromosome with the 1898 + 1G > A mutation had skipped exon 12 entirely, resulting in a joining of exons 11 and 13. Deletion of exon 12 results in the removal of a highly conserved region which encodes the Walker B consensus sequence of the first nucleotide-binding fold of CFTR. PMID- 1284541 TI - Identification of a new splicing mutation (406-1 G-C) in the CFTR gene. PMID- 1284542 TI - Identification of a novel nonsense mutation (L88X) in exon 3 of the cystic fibrosis transmembrane conductance regulator gene in a native Korean cystic fibrosis chromosome. PMID- 1284543 TI - delta F508 cystic fibrosis mutation appears very infrequently in the Greek Cypriot community of Cyprus. PMID- 1284545 TI - No CFTR: are CF symptoms milder? PMID- 1284544 TI - Observations on the interleukin-6 and acute phase protein profiles in the disease course of patients with lupus erythematosus. AB - In vitro models have shown that interleukin-6 (IL-6) is the main dominator of the stimulation of the full spectrum of acute phase proteins. This study describes IL 6 levels in relation to levels of acute phase proteins in 15 systemic lupus erythematosus (SLE) patients, with special attention given to those patients with increased serum levels of IL-6. Three episodes with elevated levels of IL-6 were observed in a period shortly after a flare-up of SLE, in three of the 15 patients. In one of these three patients a clear increase in the C-reactive protein (CRP) level, preceded by an IL-6 increase, was observed. In the other two patients, CRP levels remained unchanged. It is speculated that, next to IL-6, another signal is operative or needed for the start of an acute phase reaction. However, influences of the disease itself or of the administered therapy cannot be excluded as the cause of the described discrepancy between IL-6 and acute phase protein profiles in these two SLE patients. PMID- 1284546 TI - Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q. AB - We investigated the molecular genetics of epidermolytic hyperkeratosis (EHK), a dominant disorder characterized by epidermal blistering, hyperkeratosis, vacuolar degeneration and clumping of keratin filaments. Based on this pathology, we have excluded by linkage analysis several candidate genes for the disease; in contrast, complete linkage was obtained with the type II keratin, K1, on 12q11 q13. Linkage in this region of chromosome 12 was confirmed using several other markers, and multi-locus linkage analyses further supported this location. Keratins are excellent EHK gene candidates since their expression is specific to the suprabasal epidermal layers. In the pedigree studied here, a type II keratin gene, very probably K1, is implicated as the site of the molecular defect causing EHK. PMID- 1284547 TI - No way out. PMID- 1284548 TI - Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland. AB - Misprocessing and mislocalization of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) has been described for the major CF-causing mutation (delta F508) in heterologous expression systems in vitro. We have generated monoclonal antibodies (mAbs) to CFTR with the aim of localizing the protein and its CF variants in vivo. Of the tissues where CFTR was observed, only the sweat gland is readily available and does not undergo secondary changes due to CF disease pathology. Sweat ducts from CF patients homozygous for delta F508 did not show the typical apical membrane staining seen in control biopsies. This demonstrates that the biosynthetic arrest and intracellular retention of delta F508 CFTR initially observed in vitro does occur in vivo and emphasizes the need to focus efforts on understanding the mislocalization. PMID- 1284549 TI - Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. AB - Large-scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns-Sayre syndrome or isolated ocular myopathy who harboured a sub-population of partially deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially-encoded polypeptides were found in affected muscle fibres, but while many COX-deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely. PMID- 1284551 TI - [Multifactorial urodynamic study of 115 patients with dysuria and benign prostatic hypertrophy]. AB - Discriminant analyses based on preoperative urodynamic parameters have proved inaccurate in predicting functional results after prostatectomy. To investigate the cause of this failure, we studied a group of 115 patients consecutively referred for prostatism and selected for prostatic surgery only on clinical criteria and flow rate. A preoperative urodynamic work-up was performed, including cystometry and urethrometry. The patients were reexamined 2 months postoperatively and underwent control uroflowmetry. All preoperative urodynamic data were computed simultaneously using principal component analysis and canonical discriminant analysis. The significance of the diagrams obtained with these multifactorial analyses was more closely examined than in previous studies. The results of classification by the discriminant function demonstrating the best combination of preoperative urodynamic variables resulted in 44% of patients being correctly rated. Examination of the diagrams showed that the major cause of failure in previous studies was the great variety of urodynamic conditions in men with prostatism, which indicates a need for multifactorial interpretation of the results of urodynamic explorations. PMID- 1284550 TI - Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. AB - Non-insulin-dependent (type II) diabetes mellitus (NIDDM) is characterized by hyperglycaemia and insulin resistance, and affects nearly 5% of the general population. Inherited factors are important for its development, but the genes involved are unknown. We have identified a large pedigree in which NIDDM, in combination with a sensorineural hearing loss, is maternally inherited. The maternal inheritance and the observed decrease in mitochondrial enzyme activities of the respiratory chain indicate a genetic defect in the mitochondrial DNA. An A to G transition was identified at nucleotide 3,243, a conserved position in the mitochondrial gene for tRNA(Leu)(UUR). This mutation cosegregates with the disease in this family and is absent in controls, and indicates that a point mutation in mitochondrial DNA is a pathogenetic factor for NIDDM. PMID- 1284552 TI - [Therapeutic indications and complementary explorations in benign prostatic hypertrophy: significance of simultaneous recordings]. AB - Dysuria due to obstruction by benign prostatic hypertrophy causes an increase in the bladder work and constitutes the origin of alterations in the bladder wall. Although initially reversible, the progression towards fibrosis makes recovery increasingly incomplete the longer the treatment is delayed. The detection and evaluation of increased bladder work in the presence of early obstruction allows treatment to be instituted early in the natural history of the disease. Although clinical examination may be suggestive of bladder neck obstruction, it is neither characteristic of the bladder repercussions nor sufficient to define a population at risk. Similarly, voiding urethrography, uroflowmetry or cystomanometry, taken separately, are unable to assess bladder work early in the disease. However, bladder work can be studied by recording the voiding intravesical pressure (measured by a suprapubic catheter) in relation to the urine flow (measured by uroflowmetry). By studying the variations in voiding pressure in relation to initiation of micturition, a parameter can be defined which is useful for the therapeutic indication: the PVOP (pre-voiding opening pressure of the bladder neck), which is able to distinguish 2 mechanisms of obstruction: "compression" characterised by a raised PVOP, as in the case of benign prostatic hypertrophy, and "stenosis", with an unchanged PVOP, as in the case of urethral stricture. Re evaluation after prostatectomy shows a return to normal of the PVOP. The difficulty of routinely inserting a suprapubic catheter has led to the development of indirect approaches, particularly voiding hydrodynamic morphological or transrectal ultrasonographic methods. PMID- 1284553 TI - [Keratinizing desquamative malpighian metaplasia of the kidney pelvis. Report of a case]. AB - We report a case of keratinizing desquamative squamous metaplasia (KDSM) of the kidney pelvis. The etiopathogenic and diagnostic aspects of this rare pathology are discussed. Absence of relationship between KDSM and the carcinoma of Upper Urinary Tract, allows to suggest a conservative management. PMID- 1284554 TI - [Prostatic growth factors and benign hypertrophy of the prostate. Current knowledge and perspectives]. AB - The importance of growth factors in prostatic regulation has been demonstrated for several years. These "prostatic" growth factors are ubiquitous polypeptides which are not specific to the prostate. To date, three principal families of growth factors appear to be potentially involved in the development of benign prostatic hypertrophy: Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Transforming Growth Factor beta (TGF beta). The FGF and TGF beta families probably play a central role in the pathogenesis of benign prostatic hypertrophy. A better definition of the respective roles of growth factors and androgens in the control of prostatic growth opens up prospects for the future in the field of basic treatment of benign prostatic hypertrophy. PMID- 1284555 TI - [Benign hyperplasia of the prostate: an overview of the treatment options]. PMID- 1284556 TI - [Early diagnosis of prostatic cancer with digital rectal examination, PSA determination, and endorectal echography. Correlations with the morphologic diagnosis in 200 consecutive cases]. AB - The proposal of an early diagnosis of prostate cancer through mass screening with digital rectal examination (DRE), transrectal ultrasound (TRUS) and serum tumor markers remains controversial: there is no high risk population. No study has proven that mass screening reduces the mortality from prostate cancer. However, when clinical and biological data give arguments for the presence of a cancer, every patient requires a prostate biopsy. We have studied the Positive Predictive Value (PPV) of each test in a selected population: 200 men over 50 years of age in which rectal examination or PSA assay was suspicious were investigated. Without any reference to the prostate volume, we considered that the PSA level was "suspicious" when it reached 3 times the upper reference value, or 12 ng/ml. DRE was suspicious in 73%, comprising 50% with prostate carcinoma. PSA assay was suspicious in 65%, comprising 61% with prostate carcinoma. 88% of cancers had a suspicious DRE or PSA assay. TRUS was suspicious in 89%, comprising 45% with prostate carcinoma. Ultrasound guided core biopsies were performed in each case, and allowed a positive diagnosis in 42% of cases, whereas bilateral fine-needle cyto-aspirates were positive in 87% of histologically proven carcinomas. Cytology alone was positive in 3 patients with negative biopsies. Both results show that the PPV of a suspicious DRE associated with an elevated PSA level is 84%. An increased PSA level is correlated with a cancer in 61%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284557 TI - Do the pharmacodynamics of the nonsteroidal anti-inflammatory drugs suggest a role in the management of postoperative pain? AB - Until recently, nonsteroidal anti-inflammatory drugs (NSAIDs) were regarded as weak analgesic agents with a potent antiplatelet effect that severely limited their perioperative usefulness. However, the recent development of injectable NSAIDs has stimulated a re-evaluation of the potential role of this class of drugs in postoperative pain management. In general surgery, NSAIDs have been shown to be effective analgesics when administered after surgery, as judged by either a reduction in pain scores and/or by an opioid sparing effect. Parenteral NSAIDs alone, notably ketorolac and diclofenac, may be adequate or even preferred analgesic agents after minor surgery. In dental surgery, NSAIDs produce greater initial analgesia than steroids, although the latter produce greater suppression of swelling and less functional loss. NSAID pretreatment results in only modest suppression of swelling compared with placebo. These data suggest that the acute analgesic effects of NSAIDs in oral surgery and probably other models result from suppression of a nociceptive process, rather than a generalised anti-inflammatory effect. This view challenges the traditional association between inhibition of prostaglandin synthesis and the therapeutic effects of these drugs. The variety of NSAIDs leads to a range in half-lives from short, e.g. diclofenac (1 h), intermediate, e.g. ketorolac (5h), to long, e.g. tenoxicam (60h), which has implications for both convenience of the dosage regimen and drug accumulation. For some racemic NSAIDs (e.g. ibuprofen), metabolic 'activation' of the inactive R-enantiomer to the active S-enantiomer occurs. Renal dysfunction may increase both the plasma concentration and body residence time of NSAIDs, thereby increasing the risk of adverse effects. The concomitant effects of anaesthesia have not yet been studied. The principal concern regarding the use of perioperative NSAIDs is the risk of decreased haemostasis and wound healing. Although it has been found that NSAIDs prolong bleeding times in patients, values generally remain below the upper limits of those in generally healthy patients. Healing of gastrointestinal anastomoses may be compromised by NSAID administration but corneal healing and bone remodelling are not. There is a need for further research into the potential for renal side effects with NSAIDs in the perioperative setting, where the effects of anaesthesia and surgery may increase the risk of side effects, particularly in elderly patients. The main benefits of NSAIDs derive from opioid sparing (e.g. reduction in perioperative nausea and vomiting and improvement in ventilation), although some studies allude to an enhanced quality of analgesia from the combination compared with either NSAID or opioid alone. The question of pre- vs postinjury treatment with NSAIDs remains unresolved. PMID- 1284558 TI - Efficacy of nonsteroidal anti-inflammatory drugs in the management of postoperative pain. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are very effective for the management of acute postoperative pain. These agents can be used in combination with opioid analgesics and local anaesthetics for the relief of severe postoperative pain, when the combination results in reduced narcotic requirements and improved analgesia compared with opioids and/or local anaesthetics. NSAIDs have been shown to be effective in a wide variety of postoperative pain states, including thoracotomy, major orthopaedic surgery such as hip arthroplasty, upper and lower abdominal surgery and minor outpatient surgery. The benefits of combining NSAIDs with opioid analgesics in the immediate postoperative period include not only improved analgesia but also the benefits associated with narcotic sparing (improved respiratory function, reduction in nausea and vomiting, reduced sedation) and there is a suggestion that NSAIDs may improve not only the quality but also the speed of recovery. By adding the NSAIDs to a routine analgesic armamentarium the goal of preventing or eliminating postoperative pain, rather than treating or reducing postoperative pain, is achieved. To use these agents more effectively, further research is required to distinguish the differences between the various NSAIDs, the optimal dosage schedules and route of administration, and, finally, the cost-effectiveness and impact on the quality and speed of postoperative recovery of NSAIDs. PMID- 1284560 TI - Are perioperative nonsteroidal anti-inflammatory drugs ulcerogenic in the short term? AB - It is well documented that long term treatment with nonsteroidal anti inflammatory drugs (NSAIDs) increases the risk of peptic ulcer and that gastroduodenal mucosal erosions can be demonstrated in volunteers within 1 week of treatment initiation. However, long term studies in nonsurgical patients have not documented gastroduodenal complications within the first week of treatment. Cumulative data from controlled studies of perioperative (> or = 48 hours and < or = 7 days) treatment with NSAIDs do not suggest an increased risk of gastroduodenal complications (such as bleeding/perforation) within this time frame. We conclude that the otherwise well documented gastrointestinal side effects of prolonged treatment with NSAIDs should not hinder short term NSAID treatment for improved analgesia after surgery. PMID- 1284559 TI - Potential renal, haematological and allergic adverse effects associated with nonsteroidal anti-inflammatory drugs. AB - The major benefits of the perioperative administration of nonsteroidal anti inflammatory drugs (NSAIDs) are related to the ability of these agents to provide analgesia without cardiovascular or respiratory depression. However, there are several possible adverse effects of NSAIDs. All NSAIDs reduce the synthesis of prostaglandins by the kidneys, but their administration in the perioperative period appears to have little potential for renal toxicity when adequate hydration is maintained and renal function is not dependent on renal prostaglandins. However, NSAIDs may cause impairment of renal function in patients with conditions such as hypovolaemia, congestive cardiac failure, or hepatic cirrhosis, since renal function in these patients may be dependent on the vascular effects of prostaglandins. Platelet aggregation is inhibited by the administration of NSAIDs, and most studies of their haematological effects report that NSAIDs are associated with an increase in bleeding times. In patients with normal haemostatic function before NSAID administration, almost all indices of coagulation remain within the normal range after NSAID treatment. Most studies of perioperative blood loss have reported no significant difference between the effects of NSAIDs and placebo in this regard. The incidence of major allergic reactions in the general population appears to be small with NSAIDs. Overall, NSAIDs appear to be safe and well tolerated drugs with a valuable role to play in the treatment of postoperative pain. PMID- 1284562 TI - Differential analgesic effects of aspirin-like drugs. AB - Tissue damage, including that due to surgical manipulation, results in 2 distinct but connected changes in the pain perception pathway. Firstly, cells disintegrate at the site of tissue damage and release mediators, including prostaglandins. These mediators transform fine nerve endings, particularly high-threshold mechanoceptors, into nociceptors. In other words, fine nerve endings that are not normally activated by mechanical pressure or temperature changes become very sensitive and are depolarised after minor mechanical or thermal changes. Secondly, in the central nervous system (CNS) and, particularly, in the dorsal horn of the spinal cord, reflex activity is increased, metabolic activity of the neuronal cells is enhanced and, chronically, major rearrangements of mediator production and electrical activity of the dorsal horn cells may be observed. Both types of change contribute to the well known phenomenon of hyperalgesia, which is regularly observed in connection with tissue damage, including that produced by surgical manipulation. It has been shown that aspirin-like drugs reduce the enhanced nociceptor activity in damaged tissue, probably as a result of prostaglandin synthesis inhibition. Recently, there have been indications that these drugs may have an additional mechanism of action in the spinal cord or higher parts of the CNS. Using the pure enantiomers of flurbiprofen in pharmacodynamic experiments in the rat, we have observed that the R- and S enantiomers may exert differential analgesic effects. The R-enantiomer, which does not inhibit cyclo-oxygenase in vitro, was almost as effective as the S enantiomer, which does inhibit prostaglandin synthesis in different models of pain and nociception.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284563 TI - Rubella virus strains show no major antigenic differences. AB - To determine whether antigenic differences occur among rubella virus strains, five wild-type strains of rubella virus isolated in the UK, the USA, and in Japan between 1964 and 1987 and four attenuated vaccine strains were compared employing a panel of 28 monoclonal antibodies in neutralization, haemagglutination inhibition, enzyme immunoassay, and indirect immunofluorescence assays. No antigenic differences were detected which confirms that rubella vaccines will protect against circulating strains and that rubella antigens used in serological tests for screening and diagnosis will detect antibodies induced by all strains. PMID- 1284561 TI - Cardiovascular risks and benefits of perioperative nonsteroidal anti-inflammatory drug treatment. AB - Prostaglandins participate in the regulation of blood pressure in normotensive and hypertensive subjects; vascular tone is subject to the continuous relaxing influence of endogenous vasodilating prostaglandins. Prostaglandin I2 (PGI2; prostacyclin), probably the most important physiological modulator of vascular tone, decreases blood pressure together with a concomitant increase in cardiac output and a reduction in systemic vascular resistance secondary to peripheral vasodilation. In addition, vasodilation within the splanchnic, pulmonary and coronary vascular beds has been observed, with increased blood flow through the mesenteric, renal and coronary vascular beds. These changes in regional blood flow have been associated with the inhibition, by PGI2, of the vasoconstrictor response to sympathetic nervous stimulation and pressor hormones [noradrenaline (norepinephrine), angiotensin II]. However, other prostaglandins, such as prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), induce coronary vasoconstriction and have different effects on pulmonary artery blood pressure because of their effect on pulmonary vascular resistance. Nonsteroidal anti inflammatory drugs (NSAIDs; e.g. indomethacin) have been reported to induce hypertension parallel to a fall in cardiac output, suggesting that the underlying mechanism is an increase in systemic vascular resistance. In animal models these agents reduced regional blood flow in the ischaemic myocardium, with a corresponding increase in infarct size. Ibuprofen, which inhibits prostaglandin synthesis to a lesser extent than indomethacin, did not exert systemic or coronary haemodynamic effects. NSAIDs also provide protection in shock models but may exacerbate haemodynamic derangements and decrease survival in acute hypovolaemic hypotension. To what extent do NSAIDs and opioids influence cardiovascular status during the postoperative course and analgesic therapy? Continuous infusion of NSAIDs for analgesia had no major haemodynamic effects. Also, there were insignificant changes in indices of left heart function (cardiac output, stroke volume) and the systemic circulation (mean arterial pressure, systemic vascular resistance) following intravenous ketorolac injections, whereas cardiac output and mean arterial pressure decreased after administration of morphine. The pulmonary circulation was unaffected by ketorolac administration, whereas morphine administration induced an increase in pulmonary vascular resistance. Indices of right and left cardiac work were decreased by morphine. Thus, ketorolac produces fewer haemodynamic effects than morphine, although it is possible that some of the effects of morphine may result from morphine-induced histamine release. NSAIDs may be seen as a worthwhile gain with respect to morphine in clinical situations when hypotension is disadvantageous or when reduction in afterload is not a specific therapeutic aim. PMID- 1284564 TI - Growth and morphological changes in the small and the large intestine in piglets during the first three days after birth. AB - Growth and morphological changes in the small and the large intestine of piglets were examined during the first three days after birth. There was a 72% increase in small intestinal weight, virtually all of which occurred during the first day and was due primarily to a 115% increase in the weight of the mucosa. Associated with the tissue weight gain there was a 24% increase in small intestinal length, a 15% increase in small intestinal diameter, a 33-90% increase in villus height and a 14-51% increase in villus diameter, during the first day. The cellular population in the small intestinal mucosa, as indicated by its DNA content, increased progressively with age, and at three days had increased by 84-154%. The percentage increase in mucosal DNA content was highest in the duodenum, intermediate in the jejunum and lowest in the ileum. Histological features and tissue protein contents revealed a transient epithelial cellular swelling related to intracellular accumulation of protein on the first day. Protein accumulation was evident in the jejunum and ileum but not in the duodenum. The positions of the nuclei in the epithelial cells suggested that on the first day protein absorption was at a more advanced stage in the jejunum and the proximal ileum than in the distal ileum. Large intestinal weight increased by 33% during the first day and had doubled by the third day, and this weight gain was due to both mucosal and non-mucosal tissue growth. Villus-like structures were observed in the caecum and the proximal colon in piglets at birth and one day after birth but not in piglets three days after birth. It is speculated that such villus-like structures may have a functional significance during the transition to complete dependence on oral nutrition in newborns. PMID- 1284565 TI - Contribution of Ca(2+)-induced Ca2+ release to the [Ca2+]i transients in myocytes from guinea-pig urinary bladder. AB - 1. Smooth muscle cells from guinea-pig urinary bladder were studied at an extracellular Ca2+ concentration ([Ca2+]o) of 3.6 mM and 36 degrees C. Fluorescence of Indo-1 was used to monitor the cytosolic calcium concentration ([Ca2+]i) and its changes ([Ca2+]i transients) induced by step membrane depolarizations. 2. During a 6 s depolarization step from -60 to 0 mV [Ca2+]i increased from a resting 118 +/- 22 nM to 1150 +/- 336 nM and decayed to a sustained level of 295 +/- 62 nM. The experiments were designed to evaluate the contribution of the release of intracellularly stored Ca2+ to components of the depolarization-induced [Ca2+]i transient, i.e. 'phasic', which decayed during a maintained depolarization step, and 'tonic' which constituted the sustained elevation of [Ca2+]i above resting level. 3. A short (1 s) application of 10 mM caffeine mimicked the phasic component. After wash-out of caffeine, the subsequent depolarization induced a [Ca2+]i transient with reduced peak, the degree of suppression depending on the interval between wash-out of caffeine and depolarization. The phasic component of the depolarization and the caffeine induced [Ca2+]i transients were not additive but saturative. 4. The phasic component was largely abolished in the continuous presence of 10 mM caffeine. It was also abolished by a 10 min cell dialysis of 10 microM ryanodine from the pipette solution and was strongly reduced by dialysis of 5 microM thapsigargin. Changes of the tonic component of the depolarization-induced [Ca2+]i transient were much less pronounced with all three interventions. 5. The tonic component of the depolarization-induced [Ca2+]i transient was increased when [Ca2+]o was elevated briefly before a depolarization close to 0 mV, whereas the phasic component was not significantly changed. Similarly, brief application of 1 microM Bay K 8644 increased the tonic component several-fold without modifying significantly the phasic component. 6. It is concluded that depolarization induced influx of Ca2+ through L-type Ca2+ channels induces the release of Ca2+ from intracellular caffeine-sensitive stores which constitutes the major part of the phasic component. Ca2+ release superimposes on the effects of Ca2+ influx through L-type Ca2+ channels, the non-inactivating part of which constitutes the tonic component of the [Ca2+]i transient. Since the two processes interact, a dissection by simple subtraction is not possible. PMID- 1284566 TI - The effect of caged calcium release on the adaptation of the transduction current in chick hair cells. AB - 1. Intracellular Ca2+ concentration ([Ca2+]i) was raised by photolysis of a caged calcium compound, nitr-5, and its effects on the mechano-electrical transduction (MET) current were studied by a whole-cell patch electrode voltage clamp technique in dissociated hair cells of a chick. Nitr-5 was loaded into the hair cell by incubation with the membrane-permeable form of the compound (nitr-5 AM). 2. Photolysis of nitr-5 by ultraviolet (UV) light irradiation induced outward currents at -50 mV when recorded with a KCl-based intracellular medium without Ca2+ chelating compounds. The average amplitude of the photo-activated outward current was 115 +/- 82 pA (mean +/- S.D., n = 5). 3. The MET current generated at -50 mV showed a decay after step displacement of the hair bundle. This adaptation was accelerated after UV exposure of the cell. The adaptation was further accelerated by hyperpolarization of the membrane and was eliminated in 20-100 microM Ca2+ extracellular media. 4. The displacement-response relationship was shifted towards the positive direction after the UV irradiation. 5. The recovery of the transducer current after step displacement of the hair bundle was accelerated after UV irradiation, for both the inward-going MET current recorded at -50 mV and the outward-going MET current at +54 mV. However, the adaptation was not observed at positive membrane potentials even after the photolysis of nitr-5. 6. The extent of MET current decay was reduced or disappeared in 20-100 microM Ca2+ extracellular media and the offset time course was prolonged at the membrane potential of -50 mV. The current decay was not observed even after the photo-release of intracellular Ca2+ in 50-100 microM Ca2+ extracellular media. 7. These results (paragraphs 3-6) suggest that the MET current adaptation is accelerated by the increase of [Ca2+]i, and that Ca2+ ions entering through MET channels are essential in the development of adaptation. 8. The adaptation of the MET current was reversibly reduced in a dihydrostreptomycin (DHSM, 20-50 microM) medium. The time course of the adaptation changes lagged the changes in the MET current amplitude. 9. The adaptation developed or disappeared with a delay of 10 20 s after the introduction of either the normal-Ca2+ (2.5 mM) or the low-Ca2+ (50-100 microM) extracellular medium, respectively. These delays in the development and the subsidence of adaptation suggest a presence of a Ca2+ buffer site intracellularly between the adaptative site and the MET channel. PMID- 1284567 TI - Potentiation of inositol trisphosphate-induced Ca2+ mobilization in Xenopus oocytes by cytosolic Ca2+. AB - 1. The ability of cytosolic Ca2+ ions to modulate inositol 1,4,5-trisphosphate (Insp3)-induced Ca2+ liberation from intracellular stores was studied in Xenopus oocytes using light flash photolysis of caged InsP3. Changes in cytosolic free Ca2+ level were effected by inducing Ca2+ entry through ionophore and voltage gated plasma membrane channels and by injection of Ca2+ through a micropipette. Their effects on Ca2+ liberation were monitored by video imaging of Fluo-3 fluorescence and by voltage clamp recording of Ca(2+)-activated membrane Cl- currents. 2. Treatment of oocytes with the Ca2+ ionophores A23187 and ionomycin caused a transient elevation of cytosolic Ca2+ level when cells were bathed in Ca(2+)-free solution, which probably arose because of release of Ca2+ from intracellular stores. 3. Membrane current and Fluo-3 Ca2+ signals evoked by photoreleased InsP3 in ionophore-treated oocytes were potentiated when the intracellular Ca2+ level was elevated by raising the Ca2+ level in the bathing solution. 4. Responses to photoreleased InsP3 were similarly potentiated following activation of Ca2+ entry through voltage-gated Ca2+ channels expressed in the plasma membrane. 5. Ca(2+)-activated membrane currents evoked by depolarization developed a delayed 'hump' component during sustained photorelease of InsP3, probably because Ca2+ ions entering through the membrane channels triggered liberation of Ca2+ from intracellular stores. 6. Ba2+ and Sr2+ ions were able to substitute for Ca2+ in potentiating InsP3-mediated Ca2+ liberation. 7. Gradual photorelease of InsP3 by weak photolysis light evoked Ca2+ liberation that began at particular foci and then propagated throughout, but not beyond that area of the oocyte exposed to the light. Local elevations of intracellular Ca2+ produced by microinjection of Ca2+ acted as new foci for the initiation of Ca2+ liberation by InsP3. 8. In resting oocytes, intracellular injections of Ca2+ resulted only in localized elevation of intracellular Ca2+, and did not evoke propagating waves. 9. The results show that cytosolic Ca2+ ions potentiate the ability of InsP3 to liberate Ca2+ from intracellular stores. This process may be important for the positive feedback mechanism underlying the generation of Ca2+ spikes and waves, and for interactions between the InsP3 pathway and Ca2+ ions entering cells through voltage- and ligand-gated channels. PMID- 1284568 TI - Intracellular pathways triggered by galanin to induce contraction of pig ileum smooth muscle cells. AB - 1. In order to determine the intracellular mechanisms by which galanin induces contraction of isolated smooth muscle cells from pig ileum, we examined the effects of external Ca2+, relaxing agents, pertussis toxin and forskolin on the galanin-induced contraction and compared these effects to those observed on the cholecystokinin derivative CCK8-induced contraction. 2. Galanin induced a concentration-dependent cell contraction. The maximal contraction (24.5 +/- 2.1% of the length of resting cells) was observed at 1 nM of galanin. When cells were incubated in the simultaneous presence of concentrations of galanin (10 fM) and CCK8 (1 pM) which were ineffective alone, or galanin (10 fM) and acetylcholine (100 pM), a synergistic action was observed corresponding to a submaximal contraction. 3. Incubation of cells in Ca(2+)-free medium caused a significant decrease in galanin- but not in CCK-induced contraction. Nifedipine, a Ca2+ channel blocker, provoked a concentration-dependent inhibition of galanin-induced contraction while it had no effect on the contraction induced by CCK8. 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin. 5. When cells were pre-incubated for 3 h in the presence of 200 ng/ml of pertussis toxin, the contraction induced by galanin was abolished while the CCK-induced contraction remained unchanged. On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction. 6. These results indicate that galanin induces a concentration-dependent contraction of pig ileum smooth muscle by a direct myogenic effect. This effect of galanin involves the activation of a pertussis toxin-sensitive G protein, which results in an influx of Ca2+ into the cell. This intracellular pathway is insensitive to the relaxing effect of cAMP. PMID- 1284570 TI - [Interferon theory of schizophrenia]. AB - The author presents a literature review of the eventual role of interferon in the etiopathogenesis of schizophrenia. Research material is presented of 20 chronic schizophrenic patients treated with Hu-alpha which seems to substantiate the beneficial effects of this substance in some cases which are resistant to current treatment methods. PMID- 1284571 TI - [Influences of the products of immune response on the functions of nervous and endocrine systems]. PMID- 1284569 TI - Caffeine-induced release and reuptake of Ca2+ by Ca2+ stores in myocytes from guinea-pig urinary bladder. AB - 1. Voltage-clamped isolated smooth muscle cells from guinea-pig urinary bladder were studied with 3.6 mM extracellular Ca2+ at 36 degrees C. The fluorescence of the Ca(2+)-sensitive dye Indo-1 was used to monitor the cytosolic calcium concentration ([Ca2+]i) and its changes ([Ca2+]i transient). Fast application of caffeine (10 mM) to the cell was used to release the intracellular Ca2+ from a 'caffeine-sensitive Ca2+ store'. 2. At the holding potential -60 mV, a short (1 s) caffeine application increased [Ca2+]i within less than 1 s from the resting 118 +/- 22 nM to 1490 +/- 332 nM. Following the caffeine wash-out, [Ca2+]i fell from this peak to a subresting level of 47 +/- 12 nM, i.e. an 'undershoot' of [Ca2+]i occurred. Subsequent caffeine-induced [Ca2+]i transients had attenuated peaks suggesting that the caffeine-sensitive Ca2+ store had lost a part of the releasable Ca2+. 3. In the continuous presence of caffeine, [Ca2+]i decayed from its peak to control resting [Ca2+]i values. The wash-out of caffeine following prolonged (10-30 s) treatment also resulted in [Ca2+]i undershoot. Subsequent caffeine-induced [Ca2+]i transients were largely abolished as if the caffeine sensitive Ca2+ store had lost a large part of releasable Ca2+. During the undershoot, hyperpolarization to -100 mV did not affect [Ca2+]i. In most cells studied, recovery of [Ca2+]i from the undershoot to the resting level required depolarizations inducing Ca2+ influx through L-type Ca2+ channels. 4. Block of plasmalemmal Ca(2+)-ATPase (PMCa) with extracellular La3+ (3 mM) did not modify the decay of the [Ca2+]i transients induced by depolarization or by a 1 s caffeine application suggesting that decay rate of both is not limited by PMCa rate. La3+ abolished the undershoot of [Ca2+]i. In the continuous presence of caffeine, La3+ largely prevented the decay of [Ca2+]i. 5. When the depolarizing steps from -60 to 0 mV (160 ms duration) were applied during the period of [Ca2+]i undershoot, the half-time of decay of the corresponding [Ca2+]i transients was up to three times faster than in control. Repetitive depolarizations restored the rate of decay and [Ca2+]i recovered to the resting value. Both processes recovered along a similar time course. 6. Application of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX; 0.1 mM) or of 8-Br-cAMP (0.1 mM) did not mimic the above caffeine effects suggesting that stimulation of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCa) by cAMP dependent phosphorylation is not the underlying mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284572 TI - [Channel-forming activity at planar lipid bilayer of the membrane active polypeptide B form venom of Bungarus fasciatus]. AB - Using planar lipid bilayer formed by lecithin and cholesterol (20 and 5 mg/ml respectively in N-decane) the channel-forming activity of the membrane active polypeptide B(BMAP B) from the venom of Bungarus fasciatus was investigated. Under the existence of a voltage or a salt concentration gradient between two sides of the bilayer, unit conductance fluctuation and a decrease in steady state resistance accompanying BMAP B incorporation and channel formation were observed. By measuring the reversal potential in an asymmetric solution, the selectivity of the BMAP B-channel was estimated having a value of PK/PC1 = 1.4. Divalent cations, such as Ba2+, Ca2+ inhibited the channel activity as they did in biomembranes. These data might provide an explanation for the depolarizing effect of the membrane active polypeptide on the native membranes. PMID- 1284574 TI - The fate of "small twins": a four-year follow-up study of low birthweight and prematurely born twins. AB - This follow-up study of twins includes 35 families from the Stockholm area. One section concerns the physical and mental development of the twins. The other sections compare the development of the children with their parents' expectations of them and the parents' feelings about the delivery. Seven twin pairs (20%) in the total group were born before 37 complete gestational weeks. Thirty-seven of the twins weighed less than 2,500 g at birth; of these, 23 (9 boys and 14 girls) weighed less than 2,500g, although they were born after 37 gestational weeks. At four years of age, 22 of the 68 twins still showed some impairment of locomotor, language/speech and emotional development, as assessed by the Griffiths Mental Development Scales. All the prematurely born and small-for-date infants were in this group. There also seems to be a relationship between developmental problems and the mother's negative or ambivalent expectations concerning the twin pregnancy. PMID- 1284573 TI - [The effect of chemical agents on lysosome fusion with phagosomes and on the F actin content in murine peritoneal macrophages]. AB - The influence of natural and synthetic polyamines, phalloidin, cytochalasin D, vinblastine, colchicine, puromycin, chlorpromazine, urea, glutaraldehyde, and ethanol on the phagosome-lysosome fusion and the content of F-actin in murine peritoneal macrophages has been studied. Fluorescent phallotoxin FITC-phalloidin was used to stain F-actin. Natural polyamines (spermine, spermidine, putrescine), phalloidin, ethanol (0.1 M) stimulated the phagosome-lysosome fusion and increased the mid-content of F-actin in macrophages. Cytochalasin D, vinblastine, colchicine, puromycin, chlorpromazine, urea, glutaraldehyde, ethanol (0.15 and 0.2 M) inhibited this process and decreased the mid-content of F-actin. Possible mechanisms of the interconnection of cytoskeleton and the phagosome-lysosome fusion are discussed. PMID- 1284575 TI - [Modulation of 3,4-diaminopyridine-evoked norepinephrine release from rat hippocampal slices by activation of alpha 2-adrenoceptor]. AB - The effects of the alpha 2-adrenoceptor agonist clonidine and antagonist yohimbine were investigated on 3,4-diaminopyridine(DAP)-evoked [3H]norepinephrine ([3H]NE) release from rat hippocampal slices in the presence and absence of extracellular Ca2+. The slices were preincubated with [3H]NE and superfused in the presence of desipramine 1 mumol.L-1.[3H]overflow was evoked by addition of DAP 100 mumol.L-1 for 10 min to the superfusion medium. Clonidine and yohimbine inhibited and enhanced the 3,4-DAP-evoked [3H]NE release in a concentration dependent manner both in the presence and absence of extracellular Ca2+. The effect of yohimbine was abolished by clonidine and was additive with the effect of ruthenium red. In the presence of extracellular Ca2+ the clonidine effect was not altered by addition of omega-conotoxin GVIA 0.1 mumol.L-1 or by removal of extracellular Ca2+, suggesting that the Ca2+ entry was not involved in the modulatory mechanisms of DAP-evoked [3H]NE release by activation of alpha 2 receptor. In the absence of extracellular Ca2+ the clonidine effect was reduced by the presence of ruthenium red 10 mumol.L-1, supporting the hypothesis that alpha 2-adrenoceptor activation might affect the intracellular mechanism of Ca2+ homeostasis. PMID- 1284576 TI - Poliomyelitis immunity status in Italian and foreign subjects. PMID- 1284577 TI - Vaginal birth after caesarean section: further contribution to counteract caesarean section epidemic. PMID- 1284578 TI - [Precursors of arterial hypertension in childhood]. PMID- 1284579 TI - [Biologically active substances in nonalcholic beverages. I. The survey and statistical study of consumption in a group of young people]. PMID- 1284580 TI - [The epidemiology of HIV infections and the guidelines for prevention interventions at the school level]. PMID- 1284581 TI - [The capacity of staphylococci to metabolize citrate]. PMID- 1284582 TI - [The typing of environmental strains of Aeromonas spp]. PMID- 1284583 TI - [Microclimate studies on the operating rooms of a Rome hospital]. PMID- 1284584 TI - [The disinfection of endoscopes and the relative hygienic problems]. PMID- 1284585 TI - [The standardization of a "dot-blot" method for the molecular identification of enterovirus in environmental samples using cDNA probes]. PMID- 1284586 TI - [The effect of polymeric modification on the biological activity of pancreatic ribonuclease]. AB - The effect of modification of dextran on pharmacokinetic properties of pancreatic RNAse and on its ability to suppress the proliferation of cells has been studied. It has been shown that the basic contribution to biological activity of polymer form of RNAse is making by azo-bonds which are forming in the process of chemical bonding of the protein with dextran support. PMID- 1284587 TI - [Effects of prostatic massage on serum levels of prostatic acid phosphatase and specific antigen]. AB - We studied the influence of prostatic massage on the seric levels of acid prostatic phosphatase (PAP) and prostatic specific antigen (PSA) before and 1, 24 and 48 h after the examination. Three groups of patients were studied: 13 patients with prostatic benign hypertrophy (PBH), six patients with metastatic prostate carcinoma and 10 control patients (urinary lithiasis). We observed a significant elevation of both seric markers 1 h after prostatic massage in the PBH and control groups. In both groups, seric marker levels returned to normal values within 24 h with PAP and 48 h with PSA. We recommend to assay serum PSA and PAP with an interval of at least 48 h after rectal digital examination. PMID- 1284588 TI - [Experimental study on tea in inhibiting mutational specificity of 6 antineoplastic drugs]. AB - According to the principles of SOS response, the authors tested the mutational specificity of tea and its inhibitory effects to the mutational specificity of 6 antineoplastic drugs by using the method of mutational and anti-mutational synchronous test. The results revealed that the tea had no mutational toxicity but anti-mutation effect. It also had the inhibitory effect on mutational toxicity of 6 antineoplastic drugs, including Mitomycin C, Bleomycin, Fluorouracil, Cisdiaminodichoroplatinum, Arabinosylcytosin and Mustargen. These results have provided referential basis for further study on anti-cancer effect and clinical use of tea. PMID- 1284589 TI - Point-mutational MspI and Ile-Val polymorphisms closely linked in the CYP1A1 gene: lack of association with susceptibility to lung cancer in a Finnish study population. AB - In this study of 87 lung cancer patients, 23 patients with lung disease other than cancer, and 121 healthy controls, no association was found between the MspI restriction fragment length polymorphism (RFLP) of the CYP1A1 gene and lung cancer risk. In the lung cancer population, histological type, smoking, and occupational histories were also examined with respect to increased lung cancer risk. No association was found between the MspI RFLP in the CYP1A1 gene and any of these variables. This is in contrast to the results of an earlier report describing an association between the rare genotype m2m2 and susceptibility to lung cancer in a Japanese population; but another study in Norway found no such association. It is evident that, in the Nordic population, MspI polymorphism in the CYP1A1 gene does not indicate individual susceptibility to lung cancer. We also studied a new point mutation which has recently been closely linked to the MspI restriction site polymorphism in a Japanese study population. This mutation results in an isoleucine-valine amino acid replacement in the heme binding region of human CYP1A1. We obtained a similar linkage in our study, so the discrepancy between the Japanese and the Nordic MspI RFLP findings cannot be based on a different degree of linkage between these two point mutations. PMID- 1284590 TI - Prostate-specific antigen levels and subsequent prostate cancer: potential for screening. AB - Prostate-specific antigen levels are increased in men with prostatic disease, including prostate cancer, and have been used clinically to monitor the response of prostate cancer to therapy. More recently, prostate-specific antigen levels, usually in combination with digital rectal examination or transrectal prostatic ultrasonography, have been suggested to be useful for the detection of prostate cancer. To evaluate the association between a single serum prostate-specific antigen level and the subsequent development of prostate cancer, we measured serum levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. Levels of prostate-specific antigen were significantly higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis in the cases. The level of prostate-specific antigen decreased with increasing time to diagnosis. The mean level for prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 micrograms/liter compared to 2.4 micrograms/liter for controls (P = 0.002). The mean level for cancer cases diagnosed in years 4 through 6 following blood sampling was 9.6 micrograms/liter compared to 1.3 micrograms/liter for controls (P = 0.0002). The sensitivity and specificity of a prostate-specific antigen level > or = 4 micrograms/liter up to 3 years prior to the time of clinical diagnosis were both 75% and up to 6 years were 67% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284591 TI - Racial differences in prostate-specific antigen levels in patients with local regional prostate cancer. AB - Prostate cancer is a significant health problem for blacks. The incidence and mortality rates are higher in blacks than in whites; blacks often present with a higher stage. Prostate-specific antigen (PSA) is a very useful serum marker in prostate cancer. We analyzed data from a cohort of 161 patients to determine whether there were any racial differences in PSA levels prior to treatment in local-regional prostate cancer. The immunoradiometric method was used to determine the PSA values. The mean PSA levels were significantly higher in blacks than in whites (P = 0.022), and the difference remained significant in multivariate analysis after adjusting for stage and grade (P = 0.020). However, when analyzed further, the difference was statistically significant in one hospital (P = 0.001) and not in another (P = 0.493). Thus, our results are not unequivocal, but our data do suggest that racial differences in PSA levels not accounted for by tumor stage or grade may exist. Assuming that the data truly reflect a racial difference, the cause(s) of this difference remains to be determined. It may exist because, within each clinical stage, blacks are presenting with a higher tumor cell burden, or it may be indicative of more aggressive biological behavior. The possibility that racial differences are due to socioeconomic factors was considered by estimating median income level from zip code of residence; although a correlation between socioeconomic status and PSA level was found, racial differences remained borderline significant (P = 0.055) after adjusting for income level (in addition to stage and grade). PMID- 1284592 TI - Cloning and mapping of the alpha-adducin gene close to D4S95 and assessment of its relationship to Huntington disease. AB - The genetic defect underlying Huntington's disease (HD) has been mapped to 4p16.3. Refined localization using recombinant HD chromosome analysis and allelic association analyses have identified two distinct candidate regions. Using a cDNA hybrid selection procedure we have cloned the gene for alpha-adducin, a subunit of a cytoskeletal protein crucial for spectrin-actin membrane plasticity. This gene maps to the proximal 2.2 Mb candidate region within 20 kb of D4S95. Alleles of markers at this locus have been shown to exhibit significant linkage disequilibrium with HD. A 4 kb alpha-adducin transcript was identified which is abundantly expressed in the caudate nucleus, the site of major neuronal loss in HD. Sequencing of the brain alpha-adducin cDNA from two HD patients and an age matched control did not detect any sequence alterations specific to HD. However, we identified in brain cDNA of both patients and control samples, two alternately spliced brain exons, not previously described in the erythrocyte cDNA. A 93 bp exon is inserted in frame between codon 471 and 472 while a 34 bp exon inserted within codon 621 disrupts the frame and introduces a stop codon after 11 novel amino acids. The mapping of the adducin gene adjacent to D4S95 and its pattern of expression, as well as its potential for distinct alternately spliced variants, reinforces the necessity to accurately assess the role of the expression of this gene in the pathogenesis of HD. PMID- 1284593 TI - Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12). AB - Abasic (AP) sites in DNA are produced spontaneously and by many genotoxic agents. The repair of such damages is initiated by AP endonucleases, which are evidently ubiquitous. We employed the recently cloned cDNA, APE, that encodes the major human AP endonuclease, to isolate large genomic fragments that contain the intact APE gene. The sequence of 3 kb encompassing APE was determined (GenBank Accession No. M99703). The APE gene contains four small introns (ranging 130 to 566 bp) and five exons, the first of which is untranslated. The 0.5 kb of DNA sequence upstream of APE did revealed only a possible CCAAT box, but no other regulatory sites or a TATA box, consistent with the constitutive expression of AP endonuclease activity observed in other studies. The location of APE in the human genome was mapped to chromosome 14, bands q11.2-12, by fluorescence in situ hybridization of metaphase cells with DNA from the genomic clones and subclones. Although this locus has not been associated causally with genetic diseases of DNA repair, some translocations that affect 14q11.2-12 could compromise APE and lead to genetic instability. PMID- 1284594 TI - Genetic linkage of autosomal dominant neovascular inflammatory vitreoretinopathy to chromosome 11q13. AB - Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an inherited eye disease characterized by retinal and iris neovascularization, abnormal retinal pigmentation, anterior chamber and vitreous inflammation, cystoid macular edema, vitreous hemorrhage, and traction retinal detachment. Some of these clinical features are shared by more common, potentially blinding, conditions including diabetic retinopathy, uveitis, and retinitis pigmentosa. Elucidation of the molecular pathogenesis of ADNIV has the potential to provide insight into the mechanisms of these common disorders. One hundred and sixteen members of an eight generation family affected with ADNIV were examined. A combination of slit lamp biomicroscopy, ophthalmoscopy, and electroretinography was used to establish the diagnosis and 34 family members were found to be affected. Blood samples were obtained from thirty-three of these individuals and nine spouses and used for chromosome linkage analysis with denaturing gradient gel and short tandem repeat polymorphisms. Two markers that map to chromosome 11q13 were found to be significantly linked to the ADNIV phenotype. There were no recombinants between the disease phenotype and marker D11S527 and multipoint analysis yielded a maximum LOD score of 11.9 centered on this marker. PMID- 1284595 TI - Molecular isolation and characterization of an expressed gene from the human Y chromosome. AB - Using a positional cloning approach, we have isolated an expressed gene from a flow-sorted Y chromosome cosmid library. The isolation of this gene was based on the identification of the Y-231 cosmid that contains CpG rich sequences (HTF islands) in its human insert. The Y-231 cosmid was capable of detecting a 1.3 kb transcript in poly (A)+ RNA samples from human testis. Several cDNA clones were isolated from a human testis cDNA library constructed in lambda gt10. In addition, DNA-mediated gene transfer and restriction enzyme mapping experiments demonstrated that two functional transcriptional units are present within the Y 231 cosmid. DNA sequencing analysis showed that the largest cDNA clone contains 1075 bp of unique sequence and a poly (A) track at the 3' end of the corresponding mRNA. An open reading frame of 762 bp that encodes a predicted protein of 253 amino acids with a calculated molecular weight of 28.9 kD was identified. The Y-231 structural gene encompasses approximately 2.7 kb of genomic sequence and contains six exons that are interrupted by five introns. The Y-231 gene shares very high (97%) identity at the DNA level to a previously described Y specific gene, testis specific protein Y-encoded (TSPY) gene, suggesting the possibility that these two genes are related, if not identical. However, the TSPY gene has been postulated to be intronless. Further PCR and RT-PCR analyses of these two genes and their transcripts have provided evidence supporting the hypothesis that they are the same gene and are members of a Y-specific repeated gene family containing intronic sequences. The Y-231 (TSPY) gene is conserved in the male genome and expressed in the testis of the chimpanzee, suggesting that it may play an important role in the physiology of this organ in man and the great ape. PMID- 1284596 TI - The genomic organization of a novel regulatory myosin light chain gene (MYL5) that maps to chromosome 4p16.3 and shows different patterns of expression between primates. AB - Myosin participates in a varying repertoire of cellular functions ranging from cytokinesis, receptor capping and secretion to sarcomere contraction. In vertebrates this functional complexity is achieved through the regulated expression of gene families encoding isoproteins for each of the myosin subunits. We report here the identification and characterization of a gene (MYL5) that encodes a novel regulatory myosin light chain isoprotein and maps 700 kb from the human chromosome 4p telomere. Identical cDNAs have been isolated from human adult retina and fetal muscle cDNA libraries. A full length 519 bp open reading frame was identified in the cDNA sequence encoding a predicted protein of 173 residues. Sequence analysis of a 5.6 kb genomic region that encodes these cDNAs revealed the presence of 7 exons which span 4 kb. Expression of this gene has been detected in human adult retina, cerebellum, basal ganglia and fetal skeletal muscle. Whereas Northern analysis fails to detect transcription of this gene in human adult skeletal muscle it reveals an abundant transcript in monkey skeletal muscle. Phylogenetic comparison of the predicted proteins primary structure to those of related myosin light chains from Drosophila, rat and human reveal evolutionarily conserved structural motifs important for both calcium binding and phosphorylation. PMID- 1284597 TI - Mutation R468W of the iduronate-2-sulfatase gene in mild Hunter syndrome (mucopolysaccharidosis type II) confirmed by in vitro mutagenesis and expression. PMID- 1284598 TI - [The coupling of phosphoinositide metabolism sensitive to ACTH with the adenylate cyclase system in the synaptosomes]. AB - The effect of cAMP on the phosphoinositide metabolism increased by the ACTH, was studied in the rat brain synaptosomes. The data obtained suggest that a coupling of the phosphoinositide metabolism and the adenylate cyclase system occurs under these conditions. PMID- 1284599 TI - [Health and navigation in New Spain]. PMID- 1284600 TI - Cancer Incidence in Five Continents. Population-at-risk. PMID- 1284601 TI - Cancer Incidence in Five Continents. Age-specific and standardized incidence rates. PMID- 1284602 TI - Cancer Incidence in Five Continents. Classification. PMID- 1284603 TI - Cancer Incidence in Five Continents. Techniques of registration. PMID- 1284604 TI - Cancer Incidence in Five Continents. Coding practices. PMID- 1284605 TI - Cancer Incidence in Five Continents. Processing of data. PMID- 1284606 TI - Cancer Incidence in Five Continents. Comparability and quality of data. PMID- 1284607 TI - Cancer Incidence in Five Continents. Cumulative rate and cumulative risk. PMID- 1284608 TI - Cancer Incidence in Five Continents. Comparison between registries: age standardized rates. PMID- 1284609 TI - Cancer Incidence in Five Continents. Age-standardized incidence rates, four-digit rubrics, and age-standardized and cumulative incidence rates, three-digit rubrics. PMID- 1284610 TI - Effect of reducing agents on proteolytic and keratinolytic activity of enzymes of Microsporum gypseum. AB - The effect of sodium sulphite, cysteine, glutathione, mercaptoethanol and dithioerythritol (0.1-10 mmol l-1) on the activity of proteases of Microsporum gypseum was studied using azocasein, cross-linked bovine serum albumin and keratin as substrates. With the substrate without disulphide bonds (casein) no stimulation was found, and reducing agents inhibited proteolysis in most cases. With the remaining two substrates, all substances enhanced the activity of proteases probably through the cleavage of the substrate disulphide bonds. Sulphite was more effective than the four used thiols and enhanced the activity against serum albumin up to 3.2 times and against keratin up to 2.9 times. Using sulphitolysed sheep wool, keratinolytic activity increased after sulphitolysis of more than 20% of disulphide bonds. With the fully sulphitolysed wool the activity increased 43 times. The obtained results support the author's hypothesis on keratin degradation by sulphite excretion prior to attack by fungal proteases. Stimulation of proteolysis and keratinolysis by cleavage of disulphide bonds is not specific for dermatophytic proteases because trypsin and pronase behaved similarly in the experiments. PMID- 1284612 TI - Antibodies to neuropeptides as alternatives for peptide receptor antagonists in studies on the physiological actions of neuropeptides. PMID- 1284611 TI - [Changes of luminol-dependent chemiluminescence of rabbit peripheral blood leukocytes during incubation with a specific allergen during the development of Arthus phenomenon]. AB - The authors studied luminol-dependent chemiluminescence of rabbit peripheral blood leukocytes during the development of Arthus' phenomenon. Samples with a specific allergen were previously incubated. It was established that in this type of allergic reactions the intensity of leukocyte chemiluminescence was determined by the concentration of the allergen with which they were incubated. Small doses of the allergen stimulate and large doses inhibit it. The inhibition is linked with the direct effect of the allergen on the cells and is not attended with diminution of their viability. PMID- 1284613 TI - Synexin (annexin VII) and membrane fusion during the process of exocytotic secretion. PMID- 1284614 TI - [The clinical picture and treatment of gallbladder cancer complicated by jaundice]. PMID- 1284616 TI - Corneal Langerhans cells and ocular immunology. PMID- 1284615 TI - Inhibition of S-antigen-induced experimental autoimmune uveoretinitis by active immunization against anti-idiotypic antibody to an S-antigen epitope. AB - Experimental autoimmune uveoretinitis (EAU) was induced in rnu/+ rats by one injection of retinal S-antigen (S-Ag) in complete Freund's adjuvant. Immunization of rats, before the S-Ag challenge, with a polyclonal antibody directed at the monoclonal antibody (mAb) S2D2, prevented the development of EAU in rats at clinical and histological levels. Lymph node cells from rats hyperimmunized with this anti-idiotype (anti-Id) S2D2 antibody were stimulated in vitro by anti-Id S2D2, S-Ag, and mAb S2D2. These findings suggest that anti-S2D2 antibody acts as an internal image at the T-cell level for the epitope of S-Ag recognized by mAb S2D2 (epitope S2). From these results, it appears that cells bearing receptors for the internal image of the epitope S2, which is not pathogenic when injected emulsified in adjuvants, are able to inhibit S-Ag-induced EAU. PMID- 1284617 TI - [Pain and stress: biological protection]. AB - The biological methods of animal organism protection, the role of stress and the nociceptive signals, the hierarchy of defence mechanism--from the autonomic reflexes, neuroendocrine regulations, emotional reactions and expressions up to peculiar to the human being intellectual safeguard have been considered. The latest data on the role of tachykinins in transmission have been examined. The discovery of mediator function of "substance P" (SP), other related peptides, which coexists and realizes from the primary afferents and other terminals of SP containing, capsaicin-sensitive neurons--opened a new chapter in the neurobiology and medicine. The necessity to support the medico-biological (fundamental) experiments by the modern society is grounded. PMID- 1284618 TI - [An electrophoretic analysis of human glycoprotein hormones and their subunits]. AB - Stability of heterodimers of human glycoprotein hormones with gonadotropic and thyrotropic activities in sodium dodecylsulfate (SDS) under non-reducing conditions at low temperature permits to resolve the native molecules of these hormones in SDS-PAG and to distinguish from their dissociated subunits by electrophoretical mobility. The analysis of dimers and alpha-, beta-subunits in one polyacrylamide gel allows to detect certain human glycoprotein hormones and to study some of their physico-chemical properties. Using two polyclonal antisera against human LH and FSH by the Western blot immunoassay it was shown that heterodimers as well as alpha and beta subunits after SDS-PAGE retain antigenic activity of native hormones. The method gave possibility to characterize the specificity of the given sera to different glycoprotein hormones. PMID- 1284619 TI - Study on the formation of neural network in the tongue of Gallus domesticus (White Leghorn) as revealed by cholinesterase technique. AB - The neural network in the tongue of Gallus domesticus was visualized using a cholinesterase technique. The network of acetylcholinesterase positive nerve fibres was formed by the tortuous myelinated as well as non-myelinated, preganglionic and postganglionic nerve fibres. The network was closely associated with a chain of acetylcholinesterase positive ganglia, the nerve fibres of the fungiform, filiform, circumvallate and foliate papillae and with the fibres of the neural terminal network. PMID- 1284620 TI - Bradykinin inhibition of cyclic AMP accumulation in D384 astrocytoma cells. Evidence against a role of cyclic GMP. AB - The present studies were performed in order to examine the possible role of cyclic GMP-stimulated phosphodiesterase (cGMP-PDE) activity in the inhibitory action of the inflammatory peptide bradykinin on cyclic AMP (cAMP) accumulation in D384 cells. Bradykinin decreased the forskolin-stimulated cAMP accumulation in the presence of the phosphodiesterase inhibitor rolipram, and caused a transient 50% rise in cellular cGMP in the presence of the nonselective PDE inhibitor 3 isobutyl-1-methylxanthine (IBMX). Both basal and bradykinin-stimulated cGMP accumulation were about 8 times higher in the presence of IBMX than in the presence of rolipram. Sodium nitroprusside, which caused a 20-70-fold increase in cGMP levels reduced forskolin stimulated cAMP accumulation, whereas hydroxylamine, which maximally caused a 16-fold increase in cGMP, did not. 8 bromo-cGMP or dibutyryl cGMP had no effect on cAMP accumulation induced by forskolin. The inhibitory effect of nitroprusside was totally reversed by blocking the soluble guanylate cyclase activity by methylene blue treatment; however, the inhibitory action of bradykinin on cAMP accumulation was not changed by this treatment. Additionally, inhibition of nitric oxide synthesis, which is known to be regulated by Ca2+ and in turn stimulates cGMP production, by N omega nitro-L-arginine (L-NAME) treatment did not alter the inhibitory effect of bradykinin on forskolin-induced cAMP accumulation. These results indicate that large increases in cGMP may regulate cAMP via cGMP-PDE whereas the small increase induced by bradykinin is insufficient and that cGMP is not involved in the inhibitory action of bradykinin on cAMP levels in D384 cells. PMID- 1284622 TI - Acidic fibroblast growth factor delays in vitro ischemia-induced intracellular calcium elevation in gerbil hippocampal slices: a sign of neuroprotection. AB - Using microfluorometry, effects of acidic fibroblast growth factor (aFGF) on the in vitro ischemia-induced intracellular calcium elevation were investigated in gerbil hippocampal slices at 35 degrees C. When slices were superfused with hypoxic and glucose-free medium, the mean latency of the in vitro ischemia induced calcium elevation was 209 +/- 51 s. The addition of aFGF in medium (25 micrograms/l) delayed the calcium elevation throughout the experiments: the mean latency was 541 +/- 94 s. This retardation in calcium elevation may be indicative of neuroprotective nature of aFGF. PMID- 1284621 TI - Production and secretion of nerve growth factor by clonal striated muscle cell line, G8-1. AB - Two specific methods, Northern blot analysis using a 50 nucleotides probe to the conserved region of the nerve growth factor (NGF) gene, and enzyme immunoassay using a monoclonal biotinylated rat anti-NGF IgG-avidin conjugated peroxidase system, were used to demonstrate the production and secretion of NGF by mouse striated muscle cell line G8-1. Calcium ionophore, A23187 (0.1-1 microM), forskolin (0.1-100 microM) and dibutyryl cyclic AMP (0.1-10 mM) strongly decreased the secretion of ir-NGF. The level of NGF mRNA was decreased by veratridine, A23187, forskolin and cyclic AMP but not by cyclic GMP. Consequently, we conclude that the secretion of NGF molecules paralleled the changes of NGF mRNA levels in the cells induced by all agents tested. Carmamylcholine also decreased the level of NGF mRNA. Immunoblot analysis suggested that denatured ir-NGF molecules exist in a higher molecular weight form (22 KDa) than those of mouse submaxillary gland (13 KDa). Both Ca(2+)- and cAMP mediated mechanisms contribute to the decreased production of NGF mRNA in the cells and the consequent inhibition of secretion of NGF molecules. Finally, molecular cloning of NGF of G8-1 cells was conducted and confirmed the structure of the gene that consists of 1, 3, and 4 exons deleting exon 2. Thus, G8-1 NGF is derived from transcript B. PMID- 1284623 TI - Behavioural, biochemical and histological effects of trimethyltin (TMT) induced brain damage in the rat. AB - To assess the nature and extent of behavioural, biochemical and histological changes induced by trimethyltin (TMT), rats were treated with a single injection of TMT over a dose range of 6, 7 and 8 mg/kg i.p. Behavioural observations were performed at a minimum of 21 days after the administration of TMT. The behavioural consequences of TMT were hyperactivity in the open-field test, increased locomotor activity and deficits in passive and active avoidance behaviour, T-maze alternation and Morris Water Maze behaviour. The behavioural changes were dose dependent and were accompanied by a degree of pathological damage to the hippocampal pyramidal cells which was particularly apparent at the highest dose. The main biochemical effects of TMT involved deficits in the serotonergic and GABA-ergic systems and a decrease in M1 and M2 binding sites in the hippocampus. These results suggest that the toxic interaction of TMT with the hippocampus and other limbic brain regions may be responsible for its effect on learning and memory. PMID- 1284624 TI - Acidic fibroblast growth factor prevents death of hippocampal CA1 pyramidal cells following ischemia. AB - Ischemic insult induces neuronal death in the CA1 subfields of the hippocampus which are designated generally as the most vulnerable brain region. Recent studies have shown that acidic and basic fibroblast growth factors are potent trophic factors that support the survival of neurons in many brain regions including the hippocampus. Here we demonstrate that continuous infusion of acidic fibroblast growth factor into the lateral cerebral ventricles beginning 2 days before ischemia prevents the death of the CA1 pyramidal cells in the hippocampus of gerbils. Furthermore, delayed continuous administration of acidic fibroblast growth factor starting 5 min after ischemia is equally protective. The results suggest a possible physiological function for acidic fibroblast growth factor in the normal support of hippocampal CA1 pyramidal cells and neurons in some other brain regions in considering the broad spectrum of responsive neurons. PMID- 1284625 TI - Dinucleotide repeat polymorphism in the human fibroblast growth factor acidic (FGFA) gene on chromosome 5. PMID- 1284626 TI - Skipping of exon 5 as a consequence of the 711 + 1 G-->T mutation in the CFTR gene. PMID- 1284627 TI - Identification of a new frameshift mutation and a duplication polymorphism in the CFTR gene in the Algerian population. PMID- 1284628 TI - RFLP detected by a genomic probe from the human X-linked proteolipid protein gene, PLP. PMID- 1284630 TI - Two MspI polymorphisms within the APC gene. PMID- 1284629 TI - An MspI RFLP in the human ARNT gene, encoding a subunit of the nuclear form of the Ah (dioxin) receptor. PMID- 1284631 TI - Canine systemic lupus erythematosus. II: Antinuclear antibodies. AB - The frequency and the specificities of antinuclear antibodies (ANAb) were studied in dogs with systemic lupus erythematosus (SLE) and compared to those found in normal dogs and in dogs with various infectious diseases. Whole ANAb were detected by immunofluorescence. Anti-double-stranded DNA Ab were found in only 2% of SLE dogs, whereas anti-single-stranded DNA Ab were present in 21.4% of SLE dogs and in 26.8% of dogs with infectious disease. Antihistone Ab were frequently observed in SLE dogs (71%) and are essentially directed against trypsin-resistant epitopes of H3, H4 and H2A. The Western blots of nuclear extracts of HeLa cells were recognized mainly by type 1 Ab (30%, reacting with bands of 43, 36, 35, 34, 30 and 27 kDa) and by anti-Sm Ab (12%) associated with anti-RNP Ab. Anti-SSA and anti-SSB Ab were rare. PMID- 1284632 TI - Idiotypes of DNA-binding antibodies: recent advances. PMID- 1284633 TI - An inter-laboratory idiotype assay validation study. PMID- 1284634 TI - An idiotype systems update. PMID- 1284635 TI - The molecular biology of anti-DNA antibodies and their idiotopes. PMID- 1284636 TI - Consideration of the transgenic and other approaches to studying DNA antibodies and their idiotypes. PMID- 1284637 TI - Idiotypes, antibodies and immunopathology. PMID- 1284638 TI - Anti-DNA idiotype network: therapeutic considerations. PMID- 1284639 TI - Detection of over 98% cystic fibrosis mutations in a Celtic population. AB - We have conducted a large systematic study of 365 cystic fibrosis (CF) chromosomes in a Celtic population from Brittany, France, in which we have been able to identify more than 98% of the cystic fibrosis gene mutations. We detected 19 different CFTR mutations located in 9 exons. Eleven of these mutations have not been described previously and nine of them are presented in this study. The denaturing gradient gel electrophoresis strategy we have used, can be applied to other populations suggesting that population screening for CF on a large scale might be possible. PMID- 1284640 TI - Human cystic fibrosis transmembrane conductance regulator directed to respiratory epithelial cells of transgenic mice. AB - Human cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in transgenic mice under the control of transcriptional elements derived from the human surfactant protein C (SP-C) gene. The hCFTR mRNA was expressed in lungs and testes: in the lung, we found hCFTR mRNA in bronchiolar and alveolar epithelial cells, and CFTR protein in respiratory epithelial cells. While the level of expression of hCFTR mRNA varied, hCFTR mRNA and protein were detected in pulmonary epithelial cells of several lines. Lung weight, morphology, somatic growth and reproductive capacity were not altered by expression hCFTR in lung and testes of the transgenics. Our findings suggest that hCFTR can be safely transferred to lung epithelial cells for CF therapy. PMID- 1284641 TI - Cystic fibrosis mice. PMID- 1284642 TI - Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. AB - An important issue for in vivo gene therapy for cystic fibrosis (CF) is the percentage of cells within the CF airway that will require correction. In this study, we mixed populations of a CF airway cell line expressing either the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA (corrected cells) or a reporter gene in defined percentages. As few as 6-10% corrected cells within an epithelial sheet generated C1-transport properties similar to sheets comprised of 100% corrected cells. Cell-cell coupling may serve as the mechanism for amplification of the functional effects of corrected cells. These data suggest that in vivo correction of all CF airway cells may not be mandatory. PMID- 1284643 TI - Two steps closer to gene therapy for cystic fibrosis. PMID- 1284645 TI - Opening the gates on ion channel diseases. PMID- 1284644 TI - The murine pallid mutation is a platelet storage pool disease associated with the protein 4.2 (pallidin) gene. AB - Pallid is one of 12 independent murine mutations with a prolonged bleeding time that are models for human platelet storage pool deficiencies in which several intracellular organelles are abnormal. We have mapped the murine gene for protein 4.2 (Epb4.2) to chromosome 2 where it co-localizes with pallid. Southern blot analyses suggest that pallid is a mutation in the Epb4.2 gene. Northern blot analyses demonstrate a smaller than normal Epb4.2 transcript in affected pallid tissues, such as kidney and skin. This is the first gene defect to be associated with a platelet storage pool deficiency, and may allow the identification of a novel structure or biological pathway that influences granulogenesis. PMID- 1284646 TI - [Bacterial flora of two sources of natural mineral waters; characterization by restriction patterns of the genes coding for ribosomal RNA; specificity and biological stability]. AB - The bacterial flora of natural mineral waters was analysed using ribosomal ribonucleic acid gene restriction patterns in addition to customary identification techniques. Two springs were studied between 1989 and 1990 and six water samples per source were examined. Among the 206 bacterial strains collected at the spring, 91 (49%) were identified at species level using the API system and 99 representative strains from the two sampling points were selected for ribosomal ribonucleic acid gene restriction analysis. Forty six patterns were detected without common patterns to two springs. The bacterial association of each mineral water has a specific character (100% of specific patterns) shown by a series of patterns, not common to the other spring. This bacteriological specificity is preserved over a marked period of time, as, for each source, a great number of characteristics patterns was repeatedly found. PMID- 1284647 TI - [Is it possible to predict the anti-arrhythmic effect of beta blockers based on various relations between premature ventricular beat and the preceding cardiac cycle?]. AB - The aim of our study was to correlate betablocker effects on premature ventricular beats (PVBs) with different patterns between PVB frequency and cardiac cycle. The computer program we used correlates each PVB to the preceding cycle length in a 24-hour electrocardiogram recording. The arrhythmic patterns obtained were defined as tachycardia-dependent, indifferent and bradycardia dependent. We selected 51 patients (39 males, 12 females, mean age 52 years) with different cardiac diseases, all in sinus rhythm, with > 25 PVBs/h, characterized by PVB stability and reproducible pattern in 2 Holter monitoring recorded at a 3 5 day interval. A tachycardia-dependent pattern (TDP) was demonstrated in 20 patients; 22 patients showed an indifferent pattern (IP) and 9 a bradycardia dependent pattern (BDP). A third Holter monitoring was performed 4-5 days after nadolol administration (80 mg/day). Nadolol caused a 87.7% PVB suppression in TDP patients (p < 0.001), a 34.8% PVB reduction in IP patients (p < 0.01) and a 36.3% increase in BDP patients (NS). The different effect of nadolol on these groups was highly significant (chi 2 30.9; p < 0.0001). These results indicate that pattern definitions is useful in identifying PVB subsets which are likely to be improved, or not, by betablockers. PMID- 1284648 TI - The angiogenesis inhibitor beta-cyclodextrin tetradecasulfate inhibits ecto protein kinase activity. AB - The growth of new blood vessels plays an important role in the pathogenesis of several diseases including cancer, diabetes, and arthritis. Beta-cyclodextrin tetradecasulfate, when administered with an appropriate steroid inhibits angiogenesis, and can stimulate angiogenesis when given alone. The regulation of angiogenesis is not well understood, and the mechanism of action of beta cyclodextrin tetradecasulfate is similarly not well defined. Ecto-protein kinase activity that utilizes extracellular ATP has recently been reported on several types of cells. Human neutrophils appear to possess two distinct ecto-protein kinase activities; one that phosphorylates exogenous substrates including vitronectin and basic fibroblast growth factor, and one that phosphorylates endogenous cell-surface proteins. This report shows that beta-cyclodextrin tetradecasulfate inhibits the phosphorylation of the exogenous substrates casein, vitronectin (the major ecto-protein kinase substrate in serum), and basic fibroblast growth factor by human neutrophil ecto-protein kinase activity. In contrast, beta-cyclodextrin tetradecasulfate had no effect on the phosphorylation of endogenous cell-surface proteins by the neutrophil ecto-protein kinase activity. Ecto-protein kinase activity that was inhibited by beta-cyclodextrin tetradecasulfate was also detected on porcine aortic and human umbilical vein endothelial cells. The effects of beta-cyclodextrin tetradecasulfate on ecto protein kinase activities may play a role in its effects on angiogenesis. PMID- 1284649 TI - Application of monoclonal antibodies to blood grouping of mixed body fluids. PMID- 1284650 TI - Pathophysiological significance of brain acidic fibroblast growth factor. AB - The acidic fibroblast growth factor (aFGF) in rat cerebrospinal fluid (CSF) increased 1000 times in the 2 hr period after food intake, or intraperitoneal (IP) or intracerebroventricular (ICV) glucose infusion. It diffused into the brain parenchyma and was taken up into neurons in the hypothalamus, hippocampus, etc.... aFGF is produced in the ependymal cells and released into CSF in response to increased glucose. ICV application of aFGF dose dependently inhibits, and anti aFGF antibody facilitates food intake. IP injection of glucose 2 hr before a task that combined acquisition with passive avoidance significantly increased retention of avoidance by mice tested 24 hr later. In a Morris water maze task, IP glucose injection 2 hr before a first trial block reduced time to find and climb onto a platform hidden just below the water surface. These facilitation by glucose of affective and spatial memory were abolished by pretreatment with anti aFGF antibody applied ICV. Continuous ICV infusion of aFGF into rats also significantly increased the reliability of passive avoidance for several days. The memory facilitation by aFGF was significantly attenuated by CA1 neuron death in the hippocampus caused by 5 min ischemia of the brain, in gerbils. After food intake, centrally-released aFGF reaches the hippocampus and facilitates memory, while peripherally released cholecystokinin reaches the endings of the afferent vagal nerves in the portal vein and changes the vagal nerve activity, which modulates hippocampal activity, to lead to memory facilitation. This, however, is blocked by vagotomy below the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284651 TI - Human CD8+ T cell clone regulates autologous CD4+ myelin basic protein specific T cells. AB - Normal human CD8+ T cell clones were co-isolated from the same culture wells as CD4+ T effector cell clones specific for myelin basic protein (MBP). Microcultures from which the CD8+ clones were isolated initially proliferated weakly to whole MBP and to an MBP peptide spanning residues 90-170. This pattern of response was similar to strongly proliferating wells that yielded CD4+ T cell clones specific for the 90-170 peptide. After repeated stimulation, however, no response to MBP or MBP 90-170 was detected, even though the number of cells increased after stimulation. Phenotyping and TCR analyses revealed the presence of two CD8+, CD4-, IL-2R+ T cell isolates that expressed a single V beta gene (V beta 17) that differed from the CD4+ isolates that uniformly expressed V beta 14. One of these CD8+ clones (C9) inhibited the antigen-driven proliferation of an autologous MBP 90-170 reactive clone but not an autologous clone specific for Herpes simplex virus (HSV), without affecting MHC non-restricted mitogen responses of the same clones. Moreover, C9 did not inhibit heterologous CD4+ T cell clones specific for MBP 1-38 or 90-170. A culture supernatant of the CD8+ clone showed the same pattern but lower levels of inhibition. C9 had mild cytolytic activity when incubated at high ratios with an autologous MBP-specific CD4+ clone. Lysis was blocked completely by anti-MHC class I antibodies, but not by anti-MHC II antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284652 TI - A study of mast cells in autoimmune NZB/W F1 mice: possible relationship between mast cells and increased vascular permeability in the thymus of NZB/W F1 mice. AB - We examined the possible relationship between thymic mast cells and increased vascular permeability in the thymus of autoimmune NZB/W F1 mice. Light microscopic observation of tissue sections showed that non-autoimmune BDF1 mast cells increased with age. In contrast, autoimmune NZB/W F1 mast cells did not increase in the thymic parenchyma at the age of 9 weeks. However, NZB/W F1 mast cells resumed the age-associated increase from the age of 12 weeks and exceeded the number of BDF1 mast cells at the age of 30 weeks. Blood histamine levels of 9 week-old NZB/W F1 mice were higher than those of BDF1 mice of comparable age. Furthermore, peritoneal mast cells of NZB/W F1 mice were more sensitive to compound 48/80 than those of BDF1 mice. Increased blood histamine levels of NZB/W F1 mice seem to be due to the enhanced histamine release from mast cells. These results suggest a possible correlation between the high histamine levels by degranulation of mast cells and increased vascular permeability in the thymus of NZB/W F1 mice. PMID- 1284653 TI - Characterization of a lipopolysaccharide encoded by a recombinant Shigella sonnei plasmid in Escherichia coli K-12. AB - The genetic information to synthesize the S-specific region of Shigella sonnei phase I lipopolysaccharide (LPS) is localized on a 180 kb plasmid which is lost quite readily. A recombinant plasmid derivative remaining stable in the bacteria was shown to determine the S-specific region of the LPS which is completely identical with that of a S. sonnei phase I strain following transfer in Escherichia coli K-12. However, the length control in polysaccharide biosynthesis is lost at least partially. PMID- 1284654 TI - Antigen-antibody interactions: elucidation of the epitope and strain-specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K. AB - The C-terminal region of Pseudomonas aeruginosa strain K (PAK) pilin comprises both an epitope for the strain-specific monoclonal antibody PK99H, which blocks pilus-mediated adherence, and the adherence binding domain for buccal and tracheal epithelial cells. The PK99H epitope was located in sequence 134-140 (Asp Glu-Gln-Phe-Ile-Pro-Lys) by using a single alanine replacement analysis on the 17 residue synthetic peptide corresponding to the PAK C-terminal sequence 128-144. Indeed, a 7-residue peptide corresponding to this sequence was shown to have a similar binding affinity to that of the native conformationally constrained (disulfide bridged) 17-residue peptide. This epitope was found to contain two critical residues (Phe137 and Lys140) and one nonessential residue (Gln136). Interestingly, the peptide, Phe-Ile-Pro-Lys, which constitutes the four most important side chains for antibody binding did not bind to PK99H. It was of interest to investigate the structural basis of the strain-specificity of PK99H utilizing naturally occurring pilin sequences. Therefore, all different residues found in the sequence corresponding to the PK99H epitope of the four other strains (PAO, CD4, K122-4, and KB7) were substituted one at a time in the PAK sequence and the changes in binding affinity of these analogs to the antibody PK99H were determined by competitive ELISA. The strain-specificity of PK99H for strains PAO, K122-4, and KB7 can be explained by the accumulated sequence changes in these strains, and at least two amino acid changes were required to explain the strain-specificity of PK99H. Similarly, cross-reactivity of PK99H with CD4 can be explained by the fact that there was only one side chain responsible for decreasing binding affinity compared to the PAK sequence. PMID- 1284655 TI - [Influence of histaglobin therapy on skin tests and clinical symptoms in patients with atopic bronchial asthma]. PMID- 1284656 TI - A single nucleotide change within a plant virus satellite RNA alters the host specificity of disease induction. AB - Some RNA plant viruses contain satellite RNAs which are dependent upon their associated virus for replication and encapsidation. Some cucumber mosaic virus satellite RNAs induce chlorosis on any of several host plants, including either tobacco or tomato. The exchange of sequence domains between cDNA clones of chlorosis-inducing and non-pathogenic satellite RNAs delimited the chlorosis domain for both tobacco and tomato plants to the same region. Site-directed mutagenesis of one nucleotide (149) within this domain changed the host plant specificity for a chlorotic response to satellite RNA infection from tomato to tobacco. Within the chlorosis domain, three conserved nucleotides are either deleted or altered in all satellite RNAs that do not induce chlorosis. Deletion of one of these nucleotides (153) did not affect satellite RNA replication but rendered it non-pathogenic. Thus, two single nucleotides have been identified which play central roles in those interactions between the virus, its satellite RNA and the host plant, and together result in a specific disease state. PMID- 1284657 TI - Differential response of maize catalases and superoxide dismutases to the photoactivated fungal toxin cercosporin. AB - Many fungi of the genus Cercospora produce a light-induced, photoactivated polyketide toxin called cercosporin. In the presence of light an excited form (triplet state) of the toxin molecule is produced which, depending on the reducing potential of the environment, reacts with molecular oxygen to produce singlet oxygen and/or superoxide radicals. In this paper a system is presented for analysis of antioxidant defense gene response using purified cercosporin under conditions demonstrated to favor superoxide formation. Under the assay conditions employed, changes in total catalase activity, as well as individual isozyme protein levels generally mirrored the changes observed in corresponding steady-state RNA levels in response to applied cercosporin. In contrast, while transcript accumulation for most maize superoxide dismutases increased dramatically, both total superoxide dismutase activity and individual isozyme protein levels remained constant in all toxin treatments. In one case, the analyses indicated that there are two distinct transcripts that hybridize with a gene-specific probe for Sod3. These two transcripts responded differentially to applied toxin (levels of the larger transcript increased while the smaller decreased), whereas corresponding steady-state levels for the SOD-3 isozyme proteins remained constant. This suggests that protein turnover might play a role in the response of these SODs to activated oxygen species. PMID- 1284658 TI - Historical perspectives of collagen diseases. PMID- 1284659 TI - [The role of substance P in the modulation of myotension in paralyzed limbs after spinal transsection on rats]. AB - It is a common clinical observation that stretch reflex excitability increases progressively after spinal transsection in man, and causes many severe complications. The purpose of the present study was to investigate the role and mechanism of substance P (SP) on the spinal reflex following spinal cord transsection. We first observed the changes of spontaneous electromyography (EMG) recorded in the paralyzed limbs of spinally transsected rats, and found that the EMG amplitude increased progressively within 40 days. The results were as follows: 1) Spontaneous EMG increased significantly following intrathecal injection of 1 microgram capsaicin, and the sensitivity of EMG to capsaicin increased progressively with time. But this effect could be partly blocked by pretreatment with SP antiserum. 2) Spontaneous EMG increased significantly following intrathecal injection of SP. Yet the time course was relatively short and the amplitude of EMG was lower. These results indicate that SP in the spinal dorsal horn participates in the regulation of myotension, and it is suggested that to decrease SP content in the spinal dorsal horn or block the afferent fibers of dorsal roots might be an effective therapy to reduce the hypermyotension caused by spinal cord injury, multiple sclerosis or other reasons. PMID- 1284660 TI - Biological Functions of Acute Phase Proteins and Regulation of their Synthesis. Proceedings of a satellite symposium of the 8th International Congress of Immunology. Krakow, August 19-22, 1992. PMID- 1284661 TI - The acute phase response: overview and evidence of roles for both transcriptional and post-transcriptional mechanisms. PMID- 1284662 TI - Regulation of the rat alpha 2 macroglobulin gene by interleukin 6 and leukemia inhibitory factor. PMID- 1284663 TI - Modulation of acute phase protein synthesis by cellular growth and differentiation factors. PMID- 1284664 TI - Interferon-gamma regulates alpha 2-macroglobulin and alpha 1-antichymotrypsin expression on the pretranslational level in HepG2 cells. PMID- 1284665 TI - Adrenal hormones and the regulation of acute phase protein synthesis. PMID- 1284666 TI - Cytokine, cytokine receptors and glucocorticoid network controlling N glycosylation of acute phase proteins in vitro. PMID- 1284667 TI - Human inter-alpha-inhibitor family in acute inflammation: simultaneous synthesis of positive and negative acute-phase proteins. PMID- 1284668 TI - Role of alpha 1-microglobulin in immune response and inflammation. PMID- 1284669 TI - Fetuin--a new acute phase protein in the adult and in the fetus. PMID- 1284671 TI - Extrahepatic synthesis of acute phase proteins and their functions. PMID- 1284670 TI - Serum acute phase proteins in neuroblastoma children at diagnosis and during the clinical treatment. A preliminary report. PMID- 1284672 TI - Communication effects of prenatal alcohol exposure. AB - This paper surveys the literature on prenatal alcohol exposure. The focus is on studies of speech, language, and communication skills evidenced by children diagnosed with fetal alcohol syndrome and fetal alcohol effects. Concomitant physical, behavioral, intellectual, and learning patterns are reviewed. Symptoms presented by alcohol-exposed children are compared to those seen in other developmentally delayed children. Future needs in areas of identification, assessment, and treatment are discussed. PMID- 1284673 TI - Effects of trigeminal neurotransmitters on piglet pial arterioles. AB - We investigated effects of calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) on pial arterioles in newborn pigs. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Initial diameters were approximately 100 microns. Calcitonin-gene related peptide dilated pial arterioles by 22 +/- 8% at 10(-9)M and by 34 +/- 6% at 10(-8)M (n = 8), and this response was not significantly altered by prior administration of indomethacin (5mg/kg, iv) (n = 6) or administration of NG-methyl-L-arginine (5mg/kg, iv, and 10(-3)M in CSF) (n = 10). Substance P dilated arterioles at 10( 10)M through 10(-5)M (maximal response = 23 +/- 3%) (n = 6), and this response was unaffected by indomethacin administration (n = 6). In contrast, NG-methyl-L arginine blocked much of the pial arteriolar dilation to SP. Unlike the other two peptides, NKA did not change pial arteriolar diameter. Radioimmunoassay determinations indicated that cerebrospinal fluid levels of 6-keto-prostaglandin F1 and prostaglandin E2 did not change appreciably during application of CGRP or SP. We conclude that CGRP and SP but not NKA are dilator stimuli in the piglet pial circulation. Dilation by CGRP probably involves direct activation of receptors on vascular smooth muscle, while SP probably partially dilates pial arterioles via release of an endothelium-dependent relaxing factor. PMID- 1284674 TI - Determination of hemoglobin Bart's in alpha thalassemia traits by two-site immunoradiometric assay. I. Purification of hemoglobin Bart's and preparation of specific anti-Hb Bart's. AB - This research report describes methods for the preparation of hemolysate and the isolation and purification of hemoglobins Bart's, A, A2, E, F and H. Procedures for the preparation of anti-Hb Bart's by injecting purified Hb Bart's into rabbits is indicated in the time schedule. The rabbit antisera were evaluated by antigen-antibody reaction in agar gel. Although the antiserum reacted with Hb Bart's but not with Hb A, A2,E and H, it also cross-reacted with Hb F. After the rabbit antisera were absorbed with Hb F, the antisera were highly specific because it only reacted with Hb Bart's. The purified specific anti-Hb Bart's was labelled with radioactive 125I by chloramine-T method. After passing through Sephadex G-100 column, the 125I labelled specific anti-Hb Bart's was obtained in the first peak. This radioactive labelled anti-Hb Bart's was ready to use in the two-site immunoradiometric assay. PMID- 1284675 TI - Cerebral abscesses due to Pseudomonas pseudomallei. AB - Two cases of cerebral abscesses caused by Pseudomonas pseudomallei are reported. The first case, a 51-year-old women had a sudden onset of progressive right hemiparesis and right facial palsy and died within 7 days. Postmortem examination disclosed brain abscess in association with disseminated infection outside the central nervous system. The second case, a 9-year-old boy displayed cerebral abscesses as an isolated manifestation. Recovery occurred after treatment with ceftazidime. Review of the ten case reports of cerebral melioidosis revealed that the lesion occurred in patients of all ages and was more common in men than in women. The frontoparietal lobe was the most common location. Fever, headache, and hemiparesis were frequent clinical manifestations while seizures, ataxia were uncommon. CT scanning, serum antibody titer along with hemoculture were useful investigate tools. The importance of early diagnosis and prompt treatment is emphasized for this fatal but treatable disease. PMID- 1284676 TI - [Renal adenocarcinoma with secretion of renin, simulating a oncocytoma. Apropos of a case in a pregnant woman with histological and immunohistochemical study]. AB - The authors report a new case of primary renin-secreting renal carcinoma in a pregnant woman. The clinical, radiological and pathological findings mimicked an oncocytoma and the diagnosis was confirmed by immunohistochemical study. PMID- 1284677 TI - Early ontogeny of the vagus nerve: an analysis of the medulla oblongata and cervical spinal cord of the postnatal rat. AB - Retrograde transport of cholera toxin conjugated with horseradish peroxidase in the postnatal rat has revealed remarkable features of dendritic fields of vagal motor neurons in the medulla oblongata and cervical spinal cord during the period of early development (0-10 days). At birth, vagal motor neurons in the dorsal motor nucleus of the vagus, nucleus ambiguus, nucleus retroambigualis, nucleus dorsomedials and the spinal nucleus of the accessory nerve are small with relatively few, unbranched processes. The span of the dendritic tree is much smaller than that found in adult animals. By the postnatal Day 2 there are marked changes in the soma as well as in the dendritic tree of these neurons. There is dispersion of the cell bodies within the neuropil as well as an expansion of the total area of the brain stem occupied by these motor neurons and their dendritic processes which show extensive growth and branching. By postnatal Day 3 the most extensive proliferation of these neurons is seen and appears to represent the peak of dendritic growth of vagal motor neurons such that the area occupied by the dendritic tree of a single neuron is three times that seen in an adult rat. This proliferation gradually decreased during the subsequent seven days of early development (i.e. Days 4-10) so that by Day 10 the dendritic span of vagal motor neurons was reduced to about twice the adult size. This growth progressively decreased from Days 10 to 30 at which time adult levels were reached. Ultrastructural examination of these horseradish peroxidase labeled dendrites showed a positive correlation between the number of dendritic processes and the number of axo-dendritic synapses. This was accompanied by an increase in the number of identifiable synaptic junctions. These morphological complexities observed during the period of early development of vagal motor neurons indicate that the vagus nerve undergoes dramatic changes during the period of early development including the establishment of numerous synaptic contacts between vagal afferents and efferents in the brainstem. A number of these changes occur in developing dendritic fields of vagal motor neurons during the first three days of neonatal life. It is reasonable to assume that developmental abnormalities during this "critical period" could produce significant functional changes in the pattern of respiration as well as in the control of airway smooth muscle. PMID- 1284678 TI - c-fos mRNA in mouse brain after MPTP treatment. AB - The neurotoxin, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a transient increase of mRNA for the immediate-early gene c-fos in the mouse brain. The c-fos mRNA level is MPTP dose-dependent and is evident in all brain regions tested including striatum, hypothalamus, cortex, hippocampus, cerebellum and midbrain. There are regional differences in the time-course for the rise of c-fos mRNA. Pretreatment with deprenyl, a selective monoamine oxidase B inhibitor, pargyline, a nonselective monoamine oxidase inhibitor, or mazindol, a dopamine uptake transport inhibitor, does not prevent the c-fos mRNA increase, suggesting that the elevation is due to the action of MPTP and not its neurotoxic metabolite MPP+. PMID- 1284679 TI - Calcium-ganglioside interactions and synaptic plasticity: effect of calcium on specific ganglioside/peptide (valinomycin, gramicidin A)-complexes in mixed mono- and bilayers. AB - A controlled exchange of calcium between the extracellular space (mM Ca2+) and the neuroplasm (microM Ca2+) is considered to be an essential prerequisite for almost every stage of neuronal activity. Our research interest is focused on those compounds, which due to their physico-chemical properties and localization within the synaptic membrane might fulfill the task as neuromodulators for functional synaptic proteins. Because of this specific binding properties towards calcium and their peculiar interactions with calcium in model systems gangliosides (amphiphilic sialic acid containing glycosphingolipids) are favorite candidates for a functional involvement in synaptic transmission of information. In this study we used monolayers to investigate the molecular packing and surface potential at the air/water interface, the interaction of gangliosides with the depsipeptide valinomycin (= monovalent ion carrier), and its influenceability by calcium. Furthermore we looked at calcium effects on the single channel conductance and mean channel life-time of the monovalent ion channel gramicidin A in mixed PC/ganglioside bilayers. In pure ganglioside monolayers the addition of 0.01 mM Ca2+ induces monolayer condensation, a rise in collapse pressure (= higher film stability), a shift of phase transition (= change of conformation), and a more negative head group potential (change of electric properties). In mixed ganglioside-valinomycin monolayers the addition of Ca2+ causes phase separation and/or aggregate formation between the ganglioside and the peptide. Single channel conductance fluctuations as well as mean channel life-time were analyzed for gramicidin A incorporated into binary mixed black lipid membranes of negatively charged gangliosides (GM1, GD1a, GT1b, GMix) and neutral lecithin (DOPC) in different molar ratios. At monovalent electrolyte concentrations up to < 250 mM CsCl the single channel conductance was significantly larger in the negatively charged mixed DOPC/ganglioside membranes than in the neutral DOPC membrane. Additionally, in the presence of gangliosides the mean channel life time is increased. The addition of calcium (0.05 mM) induced a reduction of single channel conductance of gramicidin A in DOPC- and mixed DOPC/ganglioside membranes. These physico-chemical data in connection with new electromicroscopical evidences for a precise localization of calcium, a calcium pump (Ca(2+)-ATPase), a clustered arrangement of gangliosides in synaptic terminals, and biochemical results with regard to activatory nature of exogenous gangliosides for neuronal protein phosphorylation and ATPases, support the hypothesis of a modulatory function of gangliosides in synaptic transmission. PMID- 1284680 TI - Functional interactions of ligand cofactors with Escherichia coli transcription termination factor rho. II. Binding of RNA. AB - The rho protein of Escherichia coli interacts with the nascent RNA transcript while RNA polymerase is paused at specific rho-dependent termination sites on the DNA template, and (in a series of steps that are still largely undefined) brings about transcript termination at these sites. In this paper we characterize the interactions of rho with RNA and relate these interactions to the quaternary structure of the functional form of rho. We use CD spectroscopy and analytical ultracentrifugation to determine the binding interactions of rho with RNA ligands of defined length ([rC]n where n > or = 6). Rho binds to long RNA chains as a hexamer characterized by D3 symmetry. Each hexamer binds approximately 70 residues of RNA. We show by ultracentrifugation and dynamic laser light scattering that, in the presence of RNA ligands less than 22 nucleotide residues in length, rho changes its quaternary structure and becomes a homogeneous dodecamer. The dodecamer contains six strong binding sites for short RNA ligands: i.e., one site for every two rho protomers. The measured association constant of these short RNAs to rho increases with increasing (rC)n length, up to n = 9, suggesting that the binding site of each rho protomer interacts with 9 RNA nucleotide residues. Oligo (rC) ligands bound to the strong RNA binding sites on the rho dodecamer do not significantly stimulate the RNA-dependent ATPase activity of rho. Based on these features of the rho-RNA interaction and other experimental data we propose a molecular model of the interaction of rho with its cofactors. PMID- 1284681 TI - Crystallization of proton channel peptides. AB - Crystals have been grown of two similar peptides that form ion-conducting channels in diphytanoyl phosphatidylcholine bilayers. These crystals were grown by slow evaporation of the organic solvent, 2,2,2-trifluoroethanol. Crystals of one of the peptides have been characterized by X-ray diffraction, and X-ray data have been measured to 2.3 A resolution. Earlier it was proposed that the ion conducting channels formed by these peptides consist of four peptides associated as a parallel alpha-helical tetramer. On the basis of the space group and unit cell dimensions of the crystals, a packing scheme for the peptide is proposed that is consistent with a tetrameric channel. PMID- 1284682 TI - Biotechnology in transfusion medicine. AB - In an overview, this paper summarizes the new possibilities based on biotechnology, such as monoclonal antibodies and genetic engineering. Examples are given where these new techniques are already used in transfusion work. In addition, some perspectives for the future in relation to these techniques are given. PMID- 1284683 TI - Automated blood component preparation with the Opti system: three years' experience. AB - Removal of buffy coat from the red cell preparations reduces the content of microaggregates and leukocytes and decreases transfusion side effects. However, buffy coat removal is difficult to standardize when performed manually. An automated method using a new type of plastic container system, the Optipac, and a new type of device, the Optipress, greatly improves blood component production. An initial hard centrifugation of the original whole blood provides the best results, leaving approximately 20 ml of plasma and 0.5 x 10(9) leukocytes per unit of red cells suspended in 100 ml of an additive solution (SAG-M). Improved quality and standardization of the products, reduced technician time and better working conditions for the technician are the major advantages as compared to traditional manual technique. PMID- 1284684 TI - [Reduction of leukocytes and loss of erythrocytes in production of erythrocyte concentrates using the "top and bottom" principle, a comparison between the equipment combinations Biopack-U/Biotrans Separator and Optipac/Optipress]. AB - Using four different centrifugation methods, we compared the combinations of top and bottom bags and blood component separators made by Biotrans and Baxter. Compared with the cell counts of the donated blood, there remained 25% of the leukocytes and 88% of the red blood cells in the red cell preparations following application of the Biotrans system; the respective values for the Baxter system were 20% leukocytes and 85% red cells. The results were not influenced by the centrifugation method used. Thus, febrile nonhemolytic transfusion reactions and immunization against leukocyte antigens can be avoided by neither system. PMID- 1284685 TI - Improvement of the separation of blood by modification of separators Optipress and Biotrans Separator. AB - By use of the new top-and-bottom bag system and automatic separators the quality of red cell concentrates (RCC) and fresh frozen plasma (FFP) could be markedly improved. Simultaneous preparation of storable single-donor platelet concentrates (PC) resulted, however, in too high losses of red cells and plasma. Through modification of the pressure plate of the separators and variation of the residual buffy coat (BC) volumes we tried to optimize the separation in this respect. In a second study we tried to establish the preparation of platelet-rich plasma (PRP) using top-and-bottom bag systems and automatic separators. MATERIALS AND METHODS: 1st study: 149 whole-blood units (Biopack U, quadruple systems) were separated into components either with Optipress (Opt, n = 58) or with Biotrans Separator (Bio, n = 91). To Optipress additional plates, 3-6 mm thick, were attached and the residual BC volume was varied by different adjustments of the distance screw. The Biotrans Separator was used with a plane pressure plate as well as with a modified plate having a transverse groove; the residual BC volume was adjusted to 50-120 ml. 2nd study: 15 whole-blood units were separated into PRP and RCC either using the Optipress (standard version, n = 5) or the Biotrans Separator (alternating opening of clamps, standard plate, n = 10). RESULTS AND CONCLUSIONS: 1st study: Both separations could be improved. The loss of red cells was significantly lower in case of the Biotrans Separator: Bio 15.6%, Opt 25.9%, p < 0.001. Other separation parameters showed no relevant difference between both separators. 2nd study: By use of the Biotrans Separator significantly less platelets could be separated (Bio 75.1 x 10(9), Opt 87.0 x 10(9), p < 0.05), but the PRP clearly was contaminated with less leukocytes (Bio 51.0 x 10(6), Opt 458.9 x 10(6), p < 0.01). The contamination of the RCC with leukocytes (about 20%) was markedly improved in both methods when compared with conventional preparations. The mean loss of red cells was 12.8% in both methods. PMID- 1284686 TI - [Procedure for production of leukocyte depleted erythrocyte and thrombocyte concentrates (PRP method) using top and bottom bags, Optipress automated separators and a computer controlled Cryofuge 6000]. AB - PRP methods for production of WBC-poor red blood cell (RBCC) and platelet concentrates (PC) are investigated using top-and-bottom bags and Optipress separators. A standard centrifugation method (profile A) and 2 methods (profiles B and C) for a computer run centrifugation using 21 (profile B) or 19 (profile C) varying time segments and g numbers. An MS-DOS-compatible personal computer runs a Cryofuge 6000. 500 ml fresh whole blood are collected in triple and/or quadruple top-and-bottom blood bags. Samples of 163 blood donors, 163 RBCCs and 161 PCs are analyzed by a Coulter Counter T 540. Blood smears of 5 RBCCs made by profile B are evaluated. Mean WBC contamination of RBCCs produced by profiles A, B and C is found to be lower than 5 x 10(8)/RBCC. None of the 5 blood smears can be counted out completely. The full number of 100 WBCs is not detected. All WBCs found are polymorphous nuclear cells. Mononuclear cells (MNC) are not evident. PCs produced by profile B contain a mean platelet yield of (76.4 +/- 21.2) x 10(9)/PC and a WBC contamination of (1.2 +/- 0.7) x 10(7)/PC. The PCs of profile B differ significantly (p < 0.001) from those of profile A and profile C. The results show a high quality of RBCC and PC produced by PRP methods using top-and bottom blood bags and Optipress separators. Employing a computer run centrifuge, PC and RBCC contain a similar WBC contamination compared with concentrates produced by buffy coat methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284687 TI - [Differentiation of leukocytes in thrombocyte concentrates by APAAP staining]. AB - The preparation of platelet concentrates (PC) from pooled buffy coats has raised concern as to whether activation of lymphocytes might take place during the period of storage. Therefore it appears to be essential to investigate the degree of leukocyte contamination and identify the subtypes of these cells. Especially lymphocytes are of relevance as they may induce either a mixed lymphocyte reaction (MLR), the production of cytokines or a graft-versus-host reaction. As the number of leukocytes is very low we adopted the alkaline phosphatase antialkaline phosphatase (APAAP) technique to determine the composition of leukocytes. We used mouse monoclonal antibodies to specifically stain T lymphocytes, B lymphocytes, monocytes, HLA-DR-positive cells and NK cells. All subtypes could easily be identified and their relative amounts were determined. In samples from 15 PCs the percentages of T lymphocytes, B lymphocytes, monocytes, NK cells and HLA-DR-positive cells was 40.3, 6.4, 18.9, 7.2 and 17.1% of total leukocytes, respectively. The standard deviation ranged between 2 and 5%. We highly recommend this technique, which is a very sensitive method to determine leukocyte contamination in PC. PMID- 1284688 TI - [Hepatitis C virus antibodies in patients and the normal population]. AB - With regard to the controversial issue of a reduction of transfusion-associated infections by non-remunerated donations, epidemiological data on the prevalence of HIV-1, HIV-2 and hepatitis C virus (HCV) are of particular interest in our country. We investigated four sample categories: (1) healthy employees and workers from Hamburg; (2) hemodialysis patients; (3) hemato-oncological patients, and (4) blood donors, and tried to differentiate between the three disputed vectors of community-acquired (sexually or pregnancy-transmitted), nosocomial and transfusion/transplantation-associated HCV infections. We conclude from our results that--prior to the implementation of blood screening--our carefully selected 'paid blood donors' conferred no higher HCV risks than the general (working) population (0.66 vs. 0.82% HCV antibody prevalence). Besides transfusions/transplantations, significant nosocomial risks apparently exist in hemodialysis units (21.0 vs. 9.5% HCV seroprevalence in polytransfused patients). Preventive measures, e.g. separate dialysis machines for HCV-positive patients, seem to be advisable. PMID- 1284689 TI - [Comparison of erythrocyte concentrations of ATP, ADP, AMP and 2,3-BPG in storage of five different additive solutions and in serum]. AB - In this study, we compared the ability of serum and of 5 additive solutions for the liquid storage of red blood cells to preserve the cellular contents of 2,3 BPG and the adenylate nucleotides ATP, ADP and AMP. As to the adenylates, PAGGS-M showed the best results. However, the difference to SAG-M was significant only after 7 weeks. On the other hand, serum appears to be the best medium for the conservation of 2,3-BPG. Between the 1st and 3rd week of storage, the decrease of 2,3-BPG was somewhat slower in PAGGS-M and SAG-M compared with the other 3 additive solutions. PMID- 1284690 TI - [Oxygen affinity and regeneration capacity of SAG-M and PAGGS-M stored erythrocytes]. AB - In order to estimate the leftward shift of the oxygen dissociation curve of hemoglobin following storage of red blood cells (rbc) in the additive solutions SAG-M and PAGGS-M, respectively, we performed blood gas analyses after equilibrating the cells with a gas mixture containing 4% of O2 and 5% of CO2 at pH 7.4 and 37 degrees C. Additionally, we took advantage of these nearly physiological conditions to measure the recovery of the hemoglobin function in vitro. We observed a good correlation between 2,3-BPG and p50 (i.e. the oxygen tension, at which hemoglobin is half-saturated with oxygen). Within the first 3 weeks of storage, the 2,3-BPG content fell to one fifth of its original value, whereas the p50 declined from 26.6 to about 20 mm Hg. Compared to fresh cells, rbc stored for longer than 3 weeks will thus deliver 30% less oxygen to the myocardium. The rbc's ability to restore these parameters remained unchanged throughout 7 weeks of storage. PMID- 1284691 TI - [Lymphocytograms in relation to storage time of CPDA1 whole blood concentrates]. AB - Immunocompetent cells have been shown to be effective in immunosuppression after blood transfusion. The analysis of leukocytes by electronic cell counter and of lymphocyte subsets by flow cytometry in stored whole blood revealed a decay of granulocytes within the first day of storage. T-lymphocyte subpopulations and natural killer cells continuously decrease over the time of storage, whereas B lymphocytes are very stable during the first 2 weeks. After 4 weeks lymphocyte subsets had decreased by the following values: total lymphocytes 46.0%, CD3+ 78.3%, CD4+ 80.1%, CD8+ 81.3%, CD19+ 65.9%, CD16/56+ 74.8% and CD3/DR+ 89.5%. Therefore leukocyte removal should be achieved as soon as possible after collection. PMID- 1284692 TI - Hemotherapy in neonatology. AB - The intensive care of very immature preterm infants is of special significance in the treatment of neonates with blood and blood components. A new, practicable transfusion concept has been developed for this group with its high and often acute need of hemotherapeutic measures: 30-ml packs containing packed red cells of blood group 0 Rh neg, free of 'immune' anti-A/B and anti-CMV-free, or deep frozen fresh plasma of blood group AB. This concept has the advantages of simplified pretransfusional serology, reduced blood requirement with simplified storage, fresher stored blood due to more rapid turnover, reduced risk of infection through reduction in number of donors per patient, implying a reduced strain on patients and personnel, and the opportunity provided by the reduced thawing time and the eliminated risk of error to commence therapy immediately after the decision. PMID- 1284693 TI - [Determining clinical effectiveness of plasmapheresis thrombocyte preparations]. AB - Automated plasmapheresis with Haemonetics-Ultralite plasma collecting system was tested to prepare platelet-rich plasma. 19 patients with bone marrow aplasia/hypoplasia received 112 platelet-rich plasma. The efficiency of platelet transfusions was determined by corrected count increment (CCI) and resonance thrombography in correlation to the clinical situation of patients. Fever and chemotherapy did not impair the values 1 h after transfusion, but the 24-hour CCI showed a reduced survival of the transfused platelets in this group. The CCI was 11.3 1 h after transfusion and 9.5 1 day after transfusion in the patient group without any factor reducing the efficiency of transfusion. In this group, the resonance thrombography significantly improved 1 and 24 h posttransfusion compared to pretransfusion. The results demonstrate an acceptable clinical efficiency of platelet-rich plasma. PMID- 1284694 TI - [Leukocyte depletion, a comparison of the "Leukotrap in-line" filter system with a sterile added 4-bag Speacell-R-500-A filter system]. AB - Leukocytes in RBC preparations have a variety of immunologic effects in transfused patients. Not only their elimination at time of transfusion but before storage seems to be advantageous. Filtration with the Leukotrap system at the day of preparation led to an overall reduction of leukocytes of 82.2%, i.e. an average of 5.4 x 10(8) leukocytes/RBC concentrate. Filtration with a Sepacell R 500 A eliminated 99.0% of leukocytes, 3.4 x 10(7) cells remained per blood unit. The determination of lymphocyte subpopulations by flow cytometry after filtration with the Leukotrap system showed a more effective adsorption of B cells than of T and natural killer cells. PMID- 1284695 TI - [Permselect--a new substance for leukocyte elimination]. AB - Permselect particles consisting of purified plant cell wall ghosts obtained from the biomass of a suspension culture of Chenopodium album L. show a very high efficiency for leukocyte binding. A package containing 1 g dry Permselect eliminates 99-100% of leukocytes from 80 ml of fresh blood, preserved whole blood, or red blood cell concentrates. At comparable conditions Permselect shows a higher efficiency of leukocyte binding than commercial filter material (cotton, cellulose acetate). The vitality parameter of filtered erythrocytes and their stability during storage were not altered. The data are discussed with respect to causality of leukocyte binding to the pectin-containing surface of the cell wall particles. PMID- 1284696 TI - [Filtration of buffy coat-free erythrocyte suspensions in additive solution]. AB - Buffy coat-free red cell concentrates in SAG-M (RCC) were produced by BAT system (leukocyte content 132 x 10(6)/RCC). They were stored for 4 weeks and filtered by Erypur Optima (E), Sepacell R 500 B (S) und PALL RC 50 TM (P). Leukocyte depletion was very effective (E: 0.56 x 10(6)/RCC; S: 0.36 x 10(6)/RCC; P: 0.55 x 10(6)/RCC) but hemolysis was remarkable (E: 301 +/- 195; S: 127 +/- 123; P: 368 +/- 256 mg/RCC). Therefore preparation of two RCC per filter was only acceptable with S. In S and P loss of red cells was tolerable (E: 90.5; S. 41.8; P: 38.2). In contrast, E should be rinsed with sodium chloride at the end of the preparation. In E and S filtration times were short without additional pressure (E: 6.6 min; S: 4.7 min; P: 20.3 min). We conclude from our results that the use of buffy coat-free red cell concentrates in additive solution considerably reduces the problems of filtration, e.g. storage interval, leukocyte reduction, hemolysis, filtration flow. Despite this, bedside filtration is not recommended because quality assurance is necessary. PMID- 1284697 TI - [Production of rejuvenated and stable, leukocyte depleted erythrocyte concentrates using the heated centrifugation method]. AB - We report on an alternative to filtration for the preparation of leukocyte-poor red cell concentrates (LP-RCC). It is based on the method of Schneider. Using RCC with buffy coat it is comparably effective in leukocyte reduction [98.3 +/- 1.0%, (3.7 +/- 2.6) x 10(6) leukocytes] and more effective in platelet reduction (96.9 +/- 2.5%). Addition of PAGGS-M before heating (30 min, 37 degrees C) as well as after preparation significantly reduces hemolysis (free hemoglobin, LDH, HBDH) and improves the quality of the LP-RCC (ATP, 2,3-DPG) during storage for 24 h after preparation. LP-RCCs prepared with PAGGS-M after 6-day storage show still better quality than before preparation and about the same quality as LP-RCCs 24 h after conventional preparation with saline solution. In conclusion, by use of PAGGS-M and sterile docking LP-RCCs of adequate quality for 6-day storage can be prepared, improving the supply of the patients concerned. PMID- 1284698 TI - New-generation RIBA hepatitis C strip immunoblot assays. AB - Second-generation hepatitis C virus (HCV) ELISAs are currently in use in Europe and have been submitted for approval in the United States. These new assays contain additional antigens from the putative nucleocapsid and NS-3 regions of the HCV genome in addition to the c100-3 antigen present in first-generation ELISAs. A supplementary test, the second-generation RIBA HCV strip immunoblot assay (2-RIBA HCV SIA) has also been developed. The strip immunoblot assay uses four recombinant HCV antigens [5-1-1 (NS-4), c100-3 (NS-4), c33c (NS-3), and c22 3 (NS-3) (nucleocapsid)] slot blotted on nitrocellulose. Screening of random volunteer blood donors with the Ortho second-generation HCV ELISA (ORTHO HCV 2.0 ELISA) indicates that a substantial change in the repeat reactive donor population is observed with the new test. Two notable features of this change are: (1) A large number of samples reactive in the 2-RIBA HCV SIA for the second generation antigens, c33c and c22-3, are detected by the ORTHO HCV 2.0 ELISA; (2) the percentage of ORTHO HCV 2.0 ELISA reactive specimens found indeterminate (reactive for only one HCV antigen) by the 2-RIBA HCV SIA is higher than in first generation HCV ELISAs (approximately 25 vs. 5%). In addition, ORTHO HCV 2.0 ELISA repeat reactive, 2-RIBA HCV SIA indeterminate samples are dominated by reactivity to c22-3 instead of c100-3, which is the case for first-generation HCV ELISA repeat reactive samples. Resolution of 2-RIBA HCV SIA indeterminate samples as either containing anti-HCV antibodies or not, is important in both diagnostic and blood screening environments, especially where donor notification is required. Our approach to resolution of these troublesome samples evolved from initial work with HCV peptides. Early studies with an experimental strip immunoblot assay containing 5 peptides from the nucleocapsid, E2 (NS-1), NS-4, and NS-5 regions of the viral genome indicated that peptides from the nucleocapsid and NS-4 regions of the genome could provide additional evidence for the presence of anti-HCV antibodies with good specificity, but other peptides suffered from poor specificity. In addition, no immunoreactive peptide from the NS-3 (c33c) region of the virus is available, presumably because the major epitope(s) of this key second-generation antigen is a conformational determinant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284699 TI - [Effect of leukocyte depleting polyester filters on thrombocytapheresis concentrates]. AB - We studied platelet loss, leukocyte depletion, T/B cell ratio, platelet morphology and platelet function (aggregation, hypotonic shock reaction, retention and retraction) prior to and after filtration through two different polyester filters (Sepacell PL-5A, Pall PL100) as well as the posttransfusional platelet increment 1 h after transfusion in 8 pairs of single-donor platelet concentrates (Cobe Spectra, Fresenius AS 104). Leukocyte depletion was effective (>99.9%) and platelet loss acceptable in both filters, all tests showing no indication of a diminished platelet function by filtration. PMID- 1284700 TI - [Effect of storage duration and irradiation dose on in vitro aggregation of thrombocytes]. AB - We studied the influence of storage (1-5 days) and gamma irradiation (0, 25, 50, 100 Gy) on the in vitro aggregability of stored platelets. Platelet aggregation was measured using the method of Born and Breddin and the aggregating agents ADP, collagen, ristocetin and arachidonic acid. With increasing time of storage the ADP-, collagen- and ristocetin-induced platelet aggregation was significantly diminished. On the other hand, the irradiation even with 100 Gy had no additional effect. PMID- 1284701 TI - [Graft versus host disease with fatal outcome after administration of filtered erythrocyte concentrates]. AB - Transfusion-associated graft-versus-host disease (TA-GVHD) resulting from the engraftment of competent lymphocytes contained in blood products has been well described in immunocompromised patients and more recently in immunocompetent patients. Prophylactic irradiation of blood products prior to transfusion is the most efficient way to prevent TA-GVHD. Standard blood bank measures to reduce mononuclear cell contamination in red blood cell units, such as freezing, washing and filtration, may reduce the number of viable lymphocytes to prevent immunizations. However, it is unknown whether the depletion of leukocytes with these techniques would decrease the risk of TA-GVHD. In this report we describe the first case of TA-GVHD following transfusion of filtrated red blood cells given to a patient receiving cytotoxic therapy for Hodgkin's disease. PMID- 1284702 TI - Decreased formation of the complement component C4A in leukocyte-depleted stored whole blood. AB - As reported earlier, factors of the complement cascade get activated in CPD-A1 stabilized whole blood. While leukocyte depletion inhibited partially the activation of C4, it had no effect on C3a concentrations. Therefore cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even though the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities, like activation of platelets which may lead to hypercoagulability and thrombosis. PMID- 1284703 TI - Age-dependent regeneration of plasma proteins after donor plasmapheresis. AB - To analyze age-dependent effects of a plasma donation on the regeneration of plasma proteins, two groups of first-time plasma donors were selected (< 25 and > 50 years). The regeneration kinetics of different plasma proteins until 3 weeks after donation was followed up. It can be concluded that a single plasma donation has an age-dependent effect on regeneration, especially on the prolonged regeneration of cholinesterase and immunoglobulins. PMID- 1284704 TI - [Effect of plasma and plasma components on lymphocyte transformation]. AB - Blood transfusions have an immunosuppressive effect on the recipient and induce changes of several immunological parameters. We therefore studied the effect of homologous and autologous fresh plasma, fresh-frozen plasma, heparinized plasma, as well as the influence of i.v. immunoglobulins on the MLC- and mitogen-induced lymphocyte transformation. We conclude from our study that, besides unspecific mechanisms, an unknown plasma factor enriched in the immunoglobulin fraction suppresses the MLC- and mitogen-induced T-cell immune response. PMID- 1284705 TI - The role of lipoproteins in inactivation of endotoxin by serum. AB - Lipopolysaccharide (LPS)-induced release of cytokines from human monocytes can be prevented by previous interference of serum with LPS. This inactivation is a function of lipoproteins. Here we show that low-density lipoproteins as well as high-density lipoproteins can inactivate LPS. The effects of heparin and EDTA on LPS inactivation by serum are also described. PMID- 1284706 TI - Prevention of cytomegalovirus infection after organ transplantation with passive immunization. An analysis of 6 randomized clinical trials. AB - We performed a meta-analysis of 6 randomized clinical trials to study the efficacy of passive immunization against CMV in solid organ transplantation. The results indicate that passive immunization against CMV prevents (fatal) CMV disease in CMV seronegative recipients of a CMV seropositive allograft, even when treated with additional immunosuppression in case of rejections. Passive immunization with anti-CMV immunoglobulin preparations did not reduce the incidence of CMV infection or disease in CMV seropositive recipients. PMID- 1284707 TI - [Evaluating the safety with reference to intravenous tolerance of immunoglobulins]. AB - The section 'Plasmatic Blood Constituents' of DGTI (German Society for Transfusion Medicine and Immunohematology) performed four ACA (anticomplementary activity) ring tests with human immunoglobulins for intravenous application (IVIG). The laboratories carrying out the analyses presented relatively consistent ACA results for IVIG commercial preparations that were obtained by means of the ACA method elaborated based on these tests. The tolerance trials evaluating the IVIGs solely by means of in vitro tests are not sufficient to serve as safety controls since there is no clear correlation existing between the ACA values and their compatibility in the animal model (rat). PMID- 1284708 TI - The 'critical hematocrit': a figure differing from patient to patient. AB - In my opinion, the problem of a 'critical hematocrit' can be summarized in five contentions: First, it is inadmissible to label any single hemoglobin or hematocrit value as being generally acceptable, the reason being, second, that the adequate values differ between patients and sometimes also between various stages of their individual course--for instance during the intra- and the postoperative period. Third, a hemoglobin or hematocrit within the normal range constitutes a natural buffer against encroachments upon the oxygen supply from non-Hb causes. Intentional manipulation of this buffer requires a careful assessment of potential benefits vs. risks. Fourth, a patient in otherwise perfect condition tolerates a hemoglobin or hematocrit below 10 g/dl or 30%, respectively, down to approximately 8 g/dl or 25%- but tolerance is not necessarily equivalent to an optimum. And fifth, the patient most dependent on his 'hemoglobin buffer' is the individual who has to overcome troubles without the monitoring facilities of an intensive care unit, for instance in the peripheral hospital equipped only for primary care. PMID- 1284709 TI - [Critical hematocrit from the viewpoint of the clinician]. AB - The hazards of homologous blood transfusions have been controlled but not eliminated by modern blood banking methods. In addition to the possibility of transmission of infectious diseases, blood transfusion has been reported to induce immunosuppression and thereby impair the host resistance of surgical patients. Experimental and clinical research, particularly in cardiac surgery, have encouraged physicians to accept postoperative anemia. The influence of hemodilution on oxygen supply to the tissues was found to be an increase of local oxygen tension. When hematocrit is progressively lowered under normovolemic conditions, blood cell flux per time and tissue unit is maintained at a hematocrit level as low as 20 vol% as a result of an increase of red blood cell velocity. An increasing number of cardiac operations have been performed upon patients belonging to Jehova's witnesses, inducing an average hematocrit of 11 vol% during extracorporeal circulation. The outcome of these patients was similar to that of patients having received blood transfusion in order to elevate oxygen supply. Some recent studies in critically ill patients demonstrate the importance of oxygen consumption as an important criterion in estimating the effect of oxygen transport. It seems to be proven that, in presence of cardiovascular stability, elevation of the hemoglobin level above 9 g/dl does not result in an increase of oxygen utilization. In accordance with the topical literature we suggest that during the perioperative period a hemoglobin level of 8.5 g/dl will become an accepted transfusion trigger. Particular patients will tolerate even much lower levels. PMID- 1284710 TI - [The critical hemoglobin value in the therapy of chronic anemia]. AB - Adequate oxygen delivery to the tissues can usually be assured until the hemoglobin concentration falls below 7-8 g/dl in patients with chronic anemia provided their compensatory mechanisms are not impaired. Such a reduction of hemoglobin concentration is usually tolerated without symptoms at rest. Under increased physical activity or by an underlying impaired function of the lung or the cardiovascular system, adaptation to anemia may not be sufficient. For this reason the impact of anemia and the resulting hypoxemia must be assessed by determining oxygen needs at various levels of physical activity. The clinical assessment for adequate oxygenation of tissues can be sufficiently estimated by simple parameters as tachycardia, dyspnea etc. Benefits from replenishing O2 carrying capacity by transfusion must be always balanced against transfusion associated risks. Below a hemoglobin concentration of 7 g/dl oxygen transport is impeded and transfusions are necessary to avoid jeopardizing the patient by additional stressful illnesses such as fever. PMID- 1284711 TI - [The critical hemoglobin/hematocrit value in obstetrics]. AB - During pregnancy, there are characteristics changes in the hemoglobin and hematocrit values. Compared with the norm for nonpregnant women, there is an increase in the total number of erythrocytes and in the plasma volume. An overproportional increase of the latter results in hydremia. The normal physiologic range for hemoglobin during pregnancy is 11.5-13.0 (13.5) g/dl; anemia is, by definition, present when the values are under 11 g/dl and is quite common in pregnancy. Since it is caused almost exclusively (95%) by iron deficiency, iron therapy or routine iron supplementation can influence its incidence. Values outside the norm range are associated with complications during pregnancy and with growth retardation of the fetus. PMID- 1284713 TI - [Perioperative blood coagulation problems in children]. AB - During childhood preoperative coagulation diagnosis is performed to prove or to rule out an inborn coagulation disorder or an acquired von Willebrand disease. The coagulation system of the newborn differs considerably from that of the adults as well as the time in which the single parameters reach adult values. Reducing the coagulation screening to the determination of aPTT and Quick test neglects severe hemostaseological disorders easily, such as von Willebrand disease which is often observed in childhood and often combined with normal aPTT values. Sometimes children affected with hypertrophy of the adenoids have temporary aPTT prolongations combined with normal values for the other coagulation parameters possibly due to lupus inhibitors. When children with deficiencies of coagulation factors need high doses of coagulation concentrates, the number of laboratory controls may be reduced by determination of recovery and the half-life period some time before. PMID- 1284712 TI - [The critical hemoglobin value in newborn infants, infants and children]. AB - The optimum and critical hemoglobin concentrations are determined by the oxygen demand of the tissues and several oxygen transport parameters (i.e., blood flow, arterial oxygen saturation, oxygen affinity of hemoglobin, and the critical venous oxygen pressure). Most of the oxygen transport parameters change markedly during the first weeks after birth. Oxygen consumption and cardiac output in neonates are three times those of adults on a body weight basis. Due to the high oxygen affinity of fetal hemoglobin, the oxygen unloading capacity of hemoglobin in neonates is about 50% less than in adults. From oxygen transport parameters and oxygen consumption we have calculated the optimum and the critical hemoglobin concentrations for preterm and full-term neonates during the first weeks after birth. A hemoglobin concentration of 15 g/dl appears optimal for preterm and full term infants at birth as well as for adults. The calculated minimum acceptable hemoglobin concentration is 6 g/dl for children and adults, 12 g/dl for preterm infants and 11 g/dl for full-term neonates at birth. Due to the postnatal decrease in oxygen affinity, the minimum acceptable hemoglobin concentration decreases by approximately 1 g/dl/week for the first 5-6 weeks until the minimum value of 6 g/dl for children and adults is reached. The minimum hemoglobin concentration should be 2 g/dl higher in patients who require increased oxygen or suffer from other serious disorders. A minimum hemoglobin concentration of 10 g/dl is recommended in children with leukemia or other oncological disease. In infants and children with chronic hypoxemia (cyanotic congenital heart disease) the minimum hemoglobin concentration should be increased by the percentage of arterial oxygen desaturation. PMID- 1284714 TI - [Diagnostic strategies for detection of the von Willebrand syndrome]. AB - The von Willebrand disease (vWD) is the most severe coagulopathy. Because of the complex biochemical structure of the von Willebrand factor (vWF), a great number of types and subtypes of the vWD were found. A screening of vWD can only be done by examining the bleeding time, the ristocetin cofactor activity (risto) and by an immunological determination of the vWF concentration. Examinations of 200 patients with a bleeding tendency showed that the ratio vWF/risto < 0.7 indicates a high probability for an abnormal multimeric structure of vWF. The exact determination of the vWD subtype then has to be done by a SDS-agarose gel electrophoresis. In 16.8% of our patients we found a decreased vWF concentration in the platelets. These patients showed normal plasmatic coagulation factors, but a bleeding tendency and a prolonged bleeding time. For diagnosis of vWD the bleeding time, immunological determination of the vWF and the risto should be done first. If a ratio vWF/risto < 0.7 or a prolonged bleeding time with a bleeding tendency is found, the separation of the vWF multimers into plasma and platelets and the determination of the vWF concentration in platelets should be carried out for an exact diagnosis of vWD. PMID- 1284715 TI - [Autologous blood donation and erythropoiesis]. AB - Autologous blood donation before elective surgery has been widely endorsed as good transfusion practice. Although only 6% of patients undergoing elective orthopedic surgery are unable to donate 3 autologous units, 40% cannot donate 4 units because they become anemic. According to the results of our study this must be due to different problems of bone marrow dynamics, which cannot be overcome by unselected use of human recombinant erythropoietin. PMID- 1284716 TI - [Preoperative autologous blood donation in heart surgery patients: laboratory parameters with oral iron substitution]. AB - In this study we analyzed some hematologic parameters of 228 autologous blood donors at a cardiosurgic clinic. The standard schedule of drawing autologous blood at our clinic is 4 units whole blood (450 ml) and 1 unit plasma (750 ml) for a time of 5 weeks under iron substitution (equivalent to 240 mg Fe). In younger women this kind of drawing blood leads to an unacceptable decrease of hemoglobin concentration. The preoperative autologous blood donation results in an increase of erythropoiesis on the day of clinical admittance. The best parameters to supervise the hematologic situation of the outpatient autologous blood donors are the hemoglobin concentration and the hematocrit. PMID- 1284717 TI - [Hemoglobin follow-up of orthopedic autologous blood transfusion patients]. AB - Patients undergoing autologous donation prior to elective orthopedic surgery show better Hb values during the perioperative period compared to those without autologous donation, all patients in both groups receiving no homologous transfusion. The widely assumed improvement of Hb regeneration during the postoperative period according to an erythropoiesis stimulated by preoperative autologous donation is not supported by our data. PMID- 1284718 TI - [Combination of a simple hollow fiber system with leukocyte filter for production of leukocyte depleted erythrocyte concentrates and plasma]. AB - Leukocyte-depleted red cell concentrate (RCC) and plasma were separated by a hollow fiber filter system combined with a leukocyte filter without any additional devices. The RCC with 100 ml additive solution had a weight of 329 g; hematocrit was 0.55, free hemoglobin 16 mg/dl; leukocytes were (0.6 +/- 0.6) x 10(9)/l. The plasma (268 g) contained 5.4 g/dl of total protein, and only a few blood cells; clotting factor VIII activity 75%, all satisfying the guidelines. PMID- 1284719 TI - [Cryopreservation of erythrocytes with hydroxyethyl starch. In vitro results leading to an autologous retransfusion model in the dog]. AB - Although the effectiveness of hydroxyethyl starch (HES) as a cryoprotectant for human red blood cells (HRBC) is well known, no clinical application has evolved so far. In contrast to glycerol HES has the advantage of causing no hemolysis per se. This offers the opportunity of a one-step procedure without a time consuming postthaw washing procedure prior to transfusion. In this study the in vitro results obtained with red blood cells from 8 dogs (DRBC) are reported and compared to HRBC (n = 5). It turned out that DRBC had a similar 2,3-DPG and a lower ATP content. Postthaw survival in terms of saline stability differed markedly (67 +/- 6 and 86 +/- 2%, respectively). DRBC were more susceptible to hypotonic stress than HRBC. Nevertheless, after cryopreservation 91% (HRBC) and 92% (DRBC) of the original 2,3-DPG were found in the thawed RBC concentrates. PMID- 1284720 TI - Cryopreserved autologous platelet transfusions in alloimmunized patients with acute leukemia. AB - Autologous platelets of 5 alloimmunized patients with acute leukemia in remission were cryopreserved with 5% dimethylsulfoxide in liquid nitrogen and retransfused in the following therapy-induced thrombocytopenic phase. The mean platelet recovery after freezing, thawing and washing was 85 +/- 6%. The mean corrected 1 hour increment in platelet counts was 11 (4-27) x 10(9)/l, i.e. 61% in comparison with fresh platelet transfusions in other patients. In vivo function of frozen platelets was documented by improvement of the posttransfusion bleeding time. Cryopreserved autologous platelets function hemostatically and can be used even for completely refractory patients and thus permit curative antileukemic therapy. PMID- 1284721 TI - [Rheologic studies before and after therapeutic cytapheresis and plasma exchange treatment]. AB - Changes in rheological properties of human blood before and after platelet pheresis were measured in patients with myeloproliferative diseases as well as in a control group of platelet donors. Although the subjective feeling of the patients during measurement did improve, a better rheological situation could not be demonstrated by the rheological parameters used. A reduction of platelets does not influence the viscosity of whole blood or of plasma. On the other hand, the viscosities of whole blood and plasma differed significantly before and after plasma-pheresis in patients with monoclonal gammopathies. The control group comprised patients without hyperviscosity syndrome and did not show any change in rheological parameters. PMID- 1284722 TI - Two years serial lymphocytapheresis of progressive hyperleukocytosis in a patient with a non-Hodgkin's lymphoma. AB - A patient with non-Hodgkin's lymphoma was treated by ambulant lymphocytapheresis once a month over a period of 2 years and 8 months. The cytoreductive effect resulted in a decrease of white blood cells from 410/nl to 130/nl. The patient tolerated the procedure, which lasted 3-4 h, without any side effects. He could be kept in good condition by monthly apheresis. So lymphocytapheresis is a means to reduce hyperleukocytosis in patients with non-Hodgkin's lymphoma. PMID- 1284723 TI - [Therapeutic thrombocytapheresis in patients with myeloproliferative diseases with the cell separators Fresenius AS 104 and Cobe Spectra: biocompatibility and safety]. AB - We studied biocompatibility, safety and efficiency of the two cell separators AS 104 (Fresenius) and Spectra (Cobe) during therapeutic thrombocytaphereses. Although some patients have very high platelet levels and coagulation as well as circulatory equilibrium is easily disturbed, no important activation of coagulation or complement was observed. In respect to patient's safety both cell separators performed very well. PMID- 1284724 TI - [Hemorheologic findings in hyperviscosity syndrome and their modification by plasmapheresis]. AB - A patient suffering from refractory immunocytoma was treated with therapeutical plasmapheresis. To estimate the hemorheological risk during and at the end of the therapy, hemorheological measurements were performed. Hematocrit, aggregation index, filtration index, plasma viscosity, colloid osmotic pressure and protein concentrations were analyzed. The efficiency of the plasmapheresis treatment is demonstrated by the reduction of the plasma viscosity from 5.5 to 2.3 mPa (57% reduction) and of the filtration index from 43.9 to 29.7 (32% reduction). The colloid osmotic pressure decreased from 3.4 to 2.5 kPa (26% reduction), plasma protein concentration from 106 to 86 g/l (19% reduction) and IgM concentration from 100 to 82 g/l (18% reduction), while the albumin concentration remained constant. PMID- 1284725 TI - Selection of unrelated bone marrow donors: does the current procedure warrant complete MHC class II identity? AB - Bone marrow transplantation from unrelated donors is being used increasingly for the treatment of patients with leukemia and several other hematologic disorders. Selection of unrelated bone marrow donors currently relies on serological HLA identity and negative mixed lymphocyte reactions between donor/recipient pairs. As serological HLA-DP typing is not feasible, we used the HLA-DPB1 oligonucleotide typing method to investigate whether the current selection procedure can guarantee complete MHC class II identity. In 40 consecutive patients, one third (62/193) serologically HLA-A, -B, -C, -DR and -DQ identical donors were found to be MLC-negative with a relative response below 5%. HLA-DPB1 oligonucleotide typing of these MLC-negative donors revealed that again only one third (20/62) was also identical for DP with their presumptive recipients. In the majority of pairs a disparity in graft-versus-host direction or in host-versus graft direction of at least one allele was seen. These data indicate that, in spite of the strict MLC criteria used, the current procedure did not warrant complete MHC class II identity. This implies that oligotyping for DPB1 can improve matching and should be introduced for typing of volunteers. PMID- 1284726 TI - [11th International Histocompatibility Workshop 1991: Personal data for the Multiple Sclerosis Study]. AB - In our multiple sclerosis (MS) study as a part of the 11th IHWS we HLA-typed 6 MS families with 9 patients and defined the complement polymorphisms (BF, C2, C4) of these families. The aims of the study were the definition of the MS susceptibility gene and the investigation of the involvement of other factors in the etiopathogenesis of MS. The MS study of the IHWS demonstrated a strong association with HLA-DRw15 and -DWw6 in a Caucasian population. The heterozygous C2 deficiency in our family PD1 linked with the haplotype A25 B18 DR2 BFS C4A4 C4B2 confirmed by complement titration may express the participation of complement factors in the etiopathogenesis of MS resulting in immunogenetic heterogeneity of MS. Analysis of the 3 MS pairs of sisters shows the linkage of HLA with the assumed MS susceptibility gene. This could not be confirmed in the whole MS family study of the 11th IHWS. PMID- 1284727 TI - [Attempts in developing a standardized test system of immunologic reactivity]. AB - Stimulation of lymphocytes with mitogens and antigens is an established model for in vitro testing of immunoreactivity. Due to the great variability of blastogenic response the interpretation of these results is difficult. Our results suggest that multivariate experiments and statistics improve the interpretation. PMID- 1284728 TI - [Strong and weak histocompatibility antigens and immune response]. AB - In blood samples of 88 healthy donors various red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 14 different mitogens and antigens. Cluster analysis confirmed by t test and F test defined 3 distinct clusters of lymphocyte reactivity. Cluster 1 in 70% [relative risk (r.r.) 109, p < 0.001] and cluster 3 in 92% (r.r. 33, p < 0.01) showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens. Our data suggest that the patterns of both red cell and HLA antigens play a major role in defining immunoreactivity. PMID- 1284729 TI - Abbott HCV EIA 2nd generation: a new screening assay. AB - An enzyme immunoassay for the detection of antibodies against structural and nonstructural domains of the hepatitis C virus (EIA-2) was compared to a first generation test (EIA-1) that can only detect antibodies against one nonstructural antigen (c100). EIA-2 revealed elevated detection rates as assessed in high risk and patient populations as well as lower repeat reactive rates in volunteer blood donors. Research test systems proved an increase in apparent specificity. PMID- 1284730 TI - [Gene amplification with PCR and sequence specific HLA oligonucleotide typing]. AB - Genetic polymorphism in the HLA class II region has been identified by the analysis of the polymerase chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant typing kit enables HLA typing independent of gene expression and quality of lymphocytes. One of the advantages of this technique is that the definition of splits is much better than typing by serology. PMID- 1284731 TI - One year's experience with two different image analysis systems for automated reading of the contrast fluorescence test. AB - We have tested two different personal-computer-based color image analysis systems for automated reading of the microlymphocytotoxicity test (LCT) for HLA-A,B,C typing and screening. Over 17,000 single LCT reactions were prepared using the simultaneous double fluorescent variant of the LCT (contrast fluorescence test, CFT). All tests were read visually by experienced laboratory staff members. For digital image analysis, an automated scanning system was used. The reactions were first recorded on a videotape recorder using a color (CCD) videocamera und subsequently analyzed with the two different image analysis systems by specifically developed programs. Good correlation (r = 0.89) of the score values assigned by digital image analysis with the visual tray reading was obtained. Since also the other main performance characteristics of the prototype system were acceptable for routine application, we may conclude that digital image analysis is a feasible and very interesting new technique for automated evaluation of the LCT. PMID- 1284732 TI - [Automated measurement of cell destruction with the Patimed System in comparison with conventional HLA typing]. AB - HLA molecules serve as identity markers for immunocompetent cells which respond to pathogens and transplant tissue antigens to distinguish self from non-self. The continuous discovery of new HLA polymorphisms which are associated with various diseases or are involved in graft rejection continuously increases the number of HLA antigens which need to be identified for each individual. We defined the HLA class I and HLA class II antigens with the NIH standard microcytotoxicity system and compared the results with those obtained using the commercially available automated Patimed system. Our results show that serological identification of HLA antigens with the Patimed system is reliable. It can be recommended for routine as well as for research purposes. PMID- 1284733 TI - ABO-incompatible bone marrow transplantation. AB - In the past 10 years 201 HLA-identical bone marrow transplantations (BMT) were performed with major ABO incompatibility in 41 (20%) and minor ABO incompatibility in 35 (18%) patients. ABO compatibility between donor and recipient showed no influence on granulocyte and platelet recovery after BMT. Erythrocyte reconstitution was significantly (p < 0.01) delayed for about 1 week in major ABO-incompatible BMT. In addition, a pure red cell aplasia lasting for 2 5 months occurred in 6 out of 21 blood group 0 patients who received transplants of group A. The rate of graft rejection, incidence of graft-versus-host disease as well as the leukemic relapse rate were similar in ABO-compatible and ABO incompatible BMT. The probability of a 10-year survival after BMT is independent of ABO compatibility between donor and recipient. PMID- 1284734 TI - [Isoagglutinins after bone marrow transplantation with minor ABO incompatibility]. AB - Sera of 22 patients after BMT with blood group change from A to 0 were investigated. Early after BMT 59% of the patients developed a temporary anti-A whereas late after BMT none of the patients tested showed isoagglutinins against A even though the red blood cells were of type 0 and anti-B was present. The onset of these anti-A isoagglutinins correlated with production of leukocytes by the donor BM and is regarded as a sign of GvHR. Late after BMT a permanent immunological tolerance to the A antigen of the recipients' old blood group seems to exist. PMID- 1284736 TI - Immune-haemolytic anaemia (IHA) after solid organ transplantation due to rhesus antibodies of donor origin: report of 5 cases. AB - During a 3-year period we observed 5 patients who developed IHA after transplantation of solid organs (4 kidneys, 1 liver) due to irregular anti erythrocyte antibodies of donor origin (4 times anti-D, once anti-D+C). The onset of acute haemolysis was usually within 2-3 weeks after transplantation; however, 1 patient developed acute haemolysis as late as day 116 after renal transplantation. The course of the clinical and serological signs (DAT positive, 'auto'-antibodies in serum and eluate) was typical and self-limited in all cases, the function of the transplanted organ was usually not affected. All patients could be managed by transfusion of antibody-compatible blood. The administration of azathioprine (1 case) did not seem to have any beneficial effect. The causative antibodies could be demonstrated retrospectively in the serum of 1 donor. Another donor had no detectable irregular anti-erythrocyte antibodies at the time of transplantation, suggesting a secondary immune response of transplanted lymphatic tissue in this case. Both recipients of a kidney from this donor developed IHA. Serum samples of the 2 other donors were not available for investigation. We suggest that a sensitive screening for irregular anti erythrocyte antibodies in the donor's serum should be performed before any transplantation of solid organs. If such antibodies are found, organs should only be used after irradiation. However, as our experiences show, this cannot prevent IHA in each case. Once haemolysis develops, the correct serological diagnosis and the transfusion of antibody-compatible red blood cells are most important. PMID- 1284735 TI - [Acquired autoimmune hemolytic anemia after liver transplantation by "auto"-anti A and "auto"-anti-P1]. AB - A 47-year-old man (group A) received a cadaver liver from a group 0 donor. On day 8 after the transplant the recipient developed severe immune hemolysis and showed a positive direct antiglobulin test due to two antibodies (anti-A and anti-P1) of transplant donor origin. The possible mechanisms involved in "autoantibody" formation in the recipient are discussed. PMID- 1284737 TI - [Comparative study of antibody identification in the gel centrifugation test (ID Microtyping System), solid phase antiglobulin test (Solidscreen Capture R, Ready ID) and tube test]. AB - The gel centrifugation test (ID Microtyping System)--a new method for antibody screening--was compared with solid phase systems (Solidscreen, Capture R, Ready ID) and the conventional tube test. 141 different antibodies were tested and the results were compared. The ID Microtyping System identified 138 (98%) of all antibodies, the tube test 110 (78%), Capture R 86 (61%), Ready ID 79 (56%) and Solidscreen 75 (53%). The results in identification of all antibodies except cold agglutinins (n = 107) were: in the ID Microtyping System 98% (105), tube test 76% (82), Capture R 70% (75), Ready ID 68% (73) and Solidscreen 61% (65). PMID- 1284738 TI - [Superiority of the gel centrifugation method (ID System) in detection of erythrocyte antibodies]. AB - We report on the direct comparison of gel centrifugation technique and tube testing for antibody (AB) screening (ABS) under controlled routine conditions. 3,000 blood samples were screened for AB by gel centrifugation (ID-System, bromelin 37 degrees C and room temperature, indirect antiglobulin test with LISS) and a sensitive tube test (T; bromelin two-phase test 37 degrees C/room temperature and indirect antiglobulin test with 22% bovine albumin) in parallel. By ID significantly more relevant and potentially hemolytic AB (51 vs. 35 AB/1.7 vs. 1.2%) could be detected: anti-E 4, anti-C 1, anti-D 4, anti-CW 2, anti-C 2, anti-Jk (a) 2, anti-Jk (b) 1. 11 of these even remained negative in tube test when retested with increased sensitivity and taking additional (homozygous) test cells. In addition, naturally occurring but rarely hemolytic AB (35 vs. 23 AB/1.2 vs. 0.8%) were also more frequently detectable by ID: anti-Le (a) 6, anti-Le (b) 2, anti-P1 6. In contrast, only two AB were only positive in T: anti-Le (a) 1, anti-Le (ab) 1. The main disadvantage of ID was its frequent positivity (7.7 vs. 4.3%) due to irrelevant cold AB (anti-I, anti-HI, anti-H) and unspecific factors. This can be partly reduced by omission of the bromelin test at room temperature (ID 3.0%, T 1.5%) as the detection of relevant AB is not affected. The frequency of naturally occurring AB was still the same as in T (0.7%) when bromelin at room temperature was omitted in both techniques. Further advantages of ID are simplicity, small volumes of sera and reagents and easy evaluability. PMID- 1284739 TI - [Positive direct antiglobulin test (DAGT) using the gel system]. AB - In the gel test system the direct antiglobulin test (DAGT) shows a considerably higher sensitivity than in the tube test. Some 40% of gel test positive DAGTs prove to be negative when tested in the tube system. Most of the (auto )antibodies detected by gel test DAGT appear to be bound integrally to the patient's own red cells and therefore are of questionable importance in view of future blood transfusions. The high sensitivity of the gel test DAGT certainly is of interest but implicates unwanted additional work for the immune hematological laboratory. PMID- 1284740 TI - [Examination of a Berlin blood donation branch for antibodies to hepatitis C virus with the anti-HCV test and for circulating HCV-RNA using polymerase chain reaction]. AB - Hepatitis C virus (HCV) is responsible for the majority of cases of transfusion related hepatitis. We performed a first-generation anti-HCV EIA in 665 repeat and 168 first-time blood donors from Berlin. 4.7 and 4.2%, respectively, showed at least one indeterminate or positive result. We further looked for HCV genome in the plasma of 20 donors with reactive anti-HCV-EIA doing a polymerase chain reaction (nested PCR). The control group consisted of 20 patients with chronic hepatitis C. The PCR was negative in all examined blood donors, but was positive in 17 of 20 controls. These findings raise the question, if a positive anti-HCV test correlates with infectiosity. PMID- 1284742 TI - Human monoclonal antibodies for the differentiation of RhD categories. AB - With the introduction of human monoclonal antibodies against antigens of the Rh system it was possible to solve a series of problems as, for instance, the permanent availability of reagents. Another problem, the classification of D categories with a panel of specific monoclonal antibodies, also might be solved by the production of such antibodies. Especially the classification of cat. VI cells is of great importance. Here we are presenting a panel of 5 human monoclonal antibodies useful for the definition of Rh-D categories. The antibodies are designated as BS221, BS227, BS228, BS230 and BS231. By positive or negative reactions with expected category cells it is possible to determine the corresponding category. All cat. VI cells of a defined panel could be identified. Of particular interest is the antibody BS221 due to its reactivity with cat. VI cells. The fact, however, that BS221 misses the detection of some cat. VI cells indicates a further subdivision of cat. VI. PMID- 1284741 TI - Results of the DGTI workshop on the evaluation of the reactivity of monoclonal anti-D. AB - All D+ samples were detected by all monoclonal antibodies (mabs) without any problem. Very few of the 3,000 D- samples showed a +/- to ++ reaction with some of the IgG type mabs using the Coombs technique. It is still open whether these are specific reactions with weakly positive samples, which were negative with polyclonal sera. IgM type mabs detected up to 100% of the Du samples dependent on the Rh phenotype and the technique used (CCDuee > CcDuee > ccDuEe). Most of the CCDuee samples reacted very strongly and should no longer be regarded as Du. PMID- 1284743 TI - [Anti-M after transfusion as an indication of a genetic variant of the MN locus]. AB - We report a case of an anti-M antibody (titer 128) and MN red blood cells (RBC) in a 76-year-old female German patient. In our case, however, RBC showed weak reactions to human anti-M compared with strong reactions using rabbit anti-M. Papain treatment destroyed the RBC reactivity to human anti-M whereas the strong reactivity to rabbit anti-M was unchanged. This pattern was also demonstrable in the patient's son and grandson. Our results indicate the existence of a rare allele at the MN locus in this family. PMID- 1284744 TI - [Liberation of the T-antigen in bacteremia]. AB - Many microorganisms are able to produce neuraminidase, which can uncover the T antigen on red blood cells and cause hemolysis. We studied T activation in 224 patients with positive blood cultures. Only those patients were included who had real bacteremia according to clinical parameters and microbiological results. None of our patients showed T transformation. We conclude that T activation is a rare or a very passing phenomenon which has less importance in routine diagnosis of sepsis. PMID- 1284745 TI - [Detection of platelet-specific alloantigens in 400 unselected blood donors]. AB - Antibodies against platelet specific alloantigens cause neonatal alloimmune thrombocytopenia, posttransfusion purpura, and they are sometimes found in polytransfused patients. In the last few years, new alloantigens were discovered in addition to the Zw-, Bak-, and Ko-alloantigens. In order to obtain representative data for the frequency of all platelet alloantigens in the European population, we typed 400 blood donors of our institution. No significant differences between our findings and data already published were found for the antigens of the HPA-1, -2, -3, and -5 systems; however, no HPA-4b (Yuka)-positive and no Naka-negative individual was found among the 400 blood donors tested. The Siba and HPA-2b antigens proved to be identical. The 'low-frequency' alloantigen Sra was not identified among the 400 individuals tested. PMID- 1284746 TI - [Clinical and serologic studies in 34 patients with post-transfusion purpura]. AB - Posttransfusion purpura (PTP) is a rare transfusion reaction characterized by a severe bleeding tendency and thrombocytopenia which occurs approximately 1 week after transfusion of platelet-containing blood components in patients previously immunized against platelet alloantigens. 34 cases of PTP were studied. Our patients were all female with a mean age of 60.8 years (35-78 years, n = 32). The inciting blood components were whole blood (4) or red cell concentrates (28). The interval between transfusion and onset of purpura ranged from 2 to 14 days with a clear maximum at 7 and 8 days. In 11 of 13 patients (85%) transfusion was accompanied by febrile, nonhemolytic transfusion reactions. Hemorrhagic symptoms lasted 9.4 days (3-37 days, n = 16). The mean minimal platelet count was 7.1 x 10(3)/microliters [(0-28) x 10(3)/microliters, n = 29]. The platelet count rose to over 50 x 10(3)/microliters after 13.9 days (2-61 days, n = 26), over 100 x 10(3)/microliters after 17.0 days (3-75 days, n = 22). In 1 patient, PTP led to death due to intracranial hemorrhage. 22 patients were treated with corticosteroids, 20 patients with intravenous immunoglobulins (IVIG), 17 of these patients received both. Therapy with IVIG was successful in 14 of 19 patients, whereas platelet transfusions (n = 18) were not able to evaluate the platelet count. Serological analysis showed that antibodies against the HPA-1a antigen either alone (18), in combination with HLA antibodies (12) or with anti-HPA-5b (1) were responsible in 91.2%, while antibodies against other platelet antigens were rarely implicated. In elution experiments HPA-1a antibodies could be eluted from the autologous HPA-1a-negative platelets. We suppose that these antibodies had a pseudo-specificity and were involved in the destruction of the patients' own platelets. PMID- 1284747 TI - [Heparin-associated thrombocytopenia: successful therapy of patients after prospective selection of a compatible heparinoid with the heparin-induced platelet activation test]. AB - Diagnosis of HAT type II and treatment of thromboembolic complications in these patients are difficult. Recently we have developed the heparin-induced platelet activation (HIPA) assay which allows a rapid confirmation of the tentative diagnosis of HAT type II. In vitro studies with sera of 25 patients revealed cross-reactivity to the LMW heparins Fragmin, Fraxiparin and Clexane whereas a LMW heparinoid, Org 10172 (Orgaran), did not. In a prospective study this heparinoid was selected for 10 HAT patients, for whom further parenteral anticoagulation was required. In 7 of these patients who received LMW heparins prior to laboratory investigations low platelet counts persisted under treatment with LMW heparins and 2 patients developed additional thromboembolic complications. Upon treatment with Org 10172 platelet counts normalized in 9 patients, in 1 patient thrombocytopenia was unrelated to parenteral anticoagulation, in 1 patient platelet count normalized after discontinuation of Org 10172. We conclude that the HIPA assay allows the laboratory diagnosis of HAT type II and the selection of a compatible heparin or heparinoid for further parenteral anticoagulation. PMID- 1284748 TI - Case report: acute renal failure, thrombocytopenia and nonhemolytic icterus probably caused by mefenamic acid (Parkemed)-dependent antibodies. AB - A 65-year-old, previously healthy man developed acute renal failure, severe thrombocytopenia and hepatic icterus after a small dose of mefenamic acid (Parkemed). Drug-dependent antibodies reacting against platelets could be identified as the most probable cause for this acute and rapidly reversible disorder. A concomitant hemolytic reaction was not observed and accordingly no drug-dependent red cell antibodies could be demonstrated. The drug-specific antibodies were found only during the acute phase using the platelet immunofluorescence test and a solid-phase immunoassay but not with the monoclonal antibody specific immobilization of platelet antigens assay. After discontinuation of the drug the patient steadily improved and fully recovered until day 22 after admission and drug removal. The clinical course strongly suggests that drug-dependent antibodies against mefenamic acid and/or its metabolites reacting by immune complex mechanism were responsible not only for the thrombocytopenia but also for the renal and hepatic failure. PMID- 1284749 TI - [Development of HLA antibodies in thrombocyte substitution with cell separator products]. AB - In a retrospective study we investigated the development of HLA antibodies in patients who received platelet concentrates from cell separators. 118 hematological/oncological patients from the Frankfurt University Clinics were investigated. They received between 4 and 66 platelet concentrates for the duration of 30 months. All patients had a negative antibody screening on admission. 31% developed either transient (15%) or permanent (16%) lymphocytotoxic antibodies. The increasing number of platelet transfusions did not correlate with the development of HLA antibodies, but the appearance of these antibodies seemed to be dependent on the disease. Permanent antibodies appeared in 8% of patients with acute leukemia, whereas 38% of patients suffering from CL, lymphoma, MDS and myeloma produced antibodies. Some patients (18) received granulocyte transfusions as well. It is striking that 11% of these patients developed permanent and 28% transient HLA antibodies. There exist no data about recent transfusions or previous pregnancies. To lower the rate of sensitization in patients with diseases such as CL, lymphoma, MDS and myeloma, it should be discussed whether leukocyte-depleted platelet concentrates should be given to these patients. PMID- 1284750 TI - Detection of antibodies to HCV: comparison of a c100-3 EIA and the 2nd generation EIA. AB - The reactivity of 558 serum specimens in Abbott 1st and 2nd generation EIAs was compared. A significant increase in HCV seropositivity was especially found in high risk groups such as hemophiliacs (57.7 vs. 73.1%), IVDA (54.5 vs. 61.8%), HIV positives (21.8 vs. 25.5%) or patients on dialysis (15.7 vs. 16.9%). Reactivity of all sera which only reacted in the 2nd generation EIA was 'confirmed' by using supplemental research assays. In contrast, sera which were highly reactive in the c100-3 assay but could not be confirmed by Neutralization Assay were weakly positive or negative in the 2nd generation test. PMID- 1284751 TI - [Clinical importance of granulocyte-specific antibodies]. AB - Clinical and laboratory data of 184 patients with immune neutropenia were evaluated. They suffered from autoimmune neutropenia (n = 165), alloimmune neonatal neutropenia (n = 18) and from transfusion-associated lung injury (n = 1). Autoimmune neutropenia was predominantly found in patients below 3 years. Patients were usually affected by benign bacterial infections. The peripheral blood count showed normal or diminished leukocyte counts with median absolute neutrophil counts of 285 cells/microliters. Bone marrow examination revealed in 60% of the cases a hypercellular marrow with a shift to the left. In 36% the bone marrow was normal and in 4% a hypocellular marrow was found. Spontaneous remission occurred in all newborns and, so far, in 4 patients with autoimmune neutropenia. Symptomatic treatment of the infections was sufficient in most of the patients. PMID- 1284752 TI - [Clinical aspects of prenatal prevention of rhesus incompatibility]. AB - The postnatal treatment with anti-D immunoglobulin to prevent rhesus sensitization is successful in about 90% of all rhesus-negative mothers at risk. Failures derive mostly from large fetomaternal hemorrhages during the last months of pregnancy. Studies from Canada, Great Britain and Sweden have shown that the injection of an additional dosage of anti-D during the 28th to 34th week of pregnancy results in a further 90% reduction of the failure rate. Although there is only a limited number of cases of hemolytic diseases in the newborn, the cost effect ratio of this prophylactic treatment calculated for the Federal Republic of Germany shows not only a medical but also an economic benefit. PMID- 1284753 TI - [New possibilities in diagnosing hemolytic disease of newborn infants]. AB - The diagnosis and management of HDN relies on measurement of maternal anti-D, amniotic fluid analysis and fetal blood sampling by chordiocentesis. However, amniocentesis and chordiocentesis have substantial risks of fetomaternal hemorrhage and subsequent increase in maternal anti-D. In addition to quantitation the functional activity of maternal anti-D has been determined by measuring the interaction of red blood cells sensitized by maternal serum in monocyte-monolayer assays. We assessed the functional activity of anti-D by titration of the sensitized red blood cells using selected sera with rheumatoid factor (RF) as human anti-IgG. First experiments using monoclonal anti-D showed a good correlation between erythrophagocytosis and RF titers. The bilirubin-protein ratio in amniotic fluid may be of great value in predicting the severity of HDN, as shown in 94 cases with severe and 39 cases with moderate disease. Amniotic fluid analysis is complicated by the presence of hemoglobin; we developed a computer program to solve this problem. To improve the serological diagnosis of ABO incompatibility, we measured IgG-anti-A, B in 1,392 maternal and newborn sera applying a sensitive gel test with Coombs serum. Furthermore, we determined the hemolytic activity of anti-A, B by microscopic observation of the morphological changes of red blood cells. PMID- 1284754 TI - SLP assay: a rapid assay for detection of red blood cell antibodies in the serology of pregnancies. AB - A rapid manual test for the detection of red cell antibodies called SLP assay has been developed and compared with the sensitivity of the antiglobulin assay. Acid soluble proteins (SLP) from human leukocytes cause aggregation of human red blood cells. SLP represents a group of proteins consisting of 5 fractions of different positively charged macromolecules, which are able to reduce the negative charge of the red cells. Reduction of the negative charge results in a nonspecific hemagglutination of different strengths, depending on the SLP fractions used. This hemagglutination can be reversed by neutralizing the SLP with heparin. In the case of blood group-antibody-mediated aggregation the hemagglutination is nonreversible despite neutralization with heparin and remains stable for several hours. Because of the high sensitivity of the SLP assay all blood group antibodies from the IgM type as well as from the IgG type are detectable even in low concentrations. The sensitivity of the SLP assay is comparable to the antiglobulin assay. PMID- 1284755 TI - [Specificity and incidence of erythrocyte antibodies in pregnant patients with intrauterine transfusions for fetal erythroblastosis]. AB - The specificity and frequency of irregular erythrocyte alloantibodies in serum obtained from 85 pregnant women managed by a total of 480 intrauterine transfusions for treatment of fetal erythroblastosis was examined over a 4-year observation period. 138 alloantibodies reactive in the indirect antiglobulin test were detected. Their specificities were widespread. The frequency of non-anti-D alloantibodies primarily responsible for fetal immunohemolysis confirmed by elution from fetal red cells increased to 8% compared with studies performed in the 70s. 16 (19%) patients developed additional alloantibodies after onset of intrauterine transfusion therapy. Regarding the fact of the high incidence of secondarily induced alloantibodies, the high prevalence of antibody mixtures and the occurrence of rare alloantibodies against blood group antigens with weak immunogenic potency, we concluded that many of the patients were 'high responders'. Therefore the role of fetomaternal transplacental hemorrhage induced by invasive intrauterine examination methods and transfusions is discussed here. It obviously has to be considered as the main cause of the immunohematologic complications. PMID- 1284756 TI - [Incidence of the detection of erythrocyte antibodies in relation to screening test cells]. AB - A variety of antibody screening tests are available to detect immunization in patients' sera. However, antibodies can be observed only if corresponding antigens are present on test cells used by an antibody screen. By comparing available test cell kits of different manufacturers we revealed various specificities of antigens present or absent on these cells. Using by an antibody screen Wr(a+), Co(b+) and Kp(a+) test cells additionally to available test cells, we detected in 1000 sera of patients 13 anti-Wr(a) and 1 anti-Co(b) besides 17 antibodies with different specificities. PMID- 1284757 TI - [Granulocyte-specific and HLA antibodies in pregnancy: incidence and clinical value]. AB - Postpartum sera of 1,016 unselected women were examined for granulocyte-specific and HLA antibodies. A total of 11 out of 1,016 sera (1.1%) were only reactive with neutrophils. Cytotoxic HLA antibodies were detected in 24%, noncytotoxic HLA antibodies in 4.8% of the sera. All antibodies belonged to the IgG 1 and IgG 3 subclasses. NA1 and NB1 specificity were each determined in one serum, two sera contained NA2-specific antibodies. After 1 year all antibodies were no more detectable. As none of the newborns from immunized mothers developed neutropenia, the incidence of alloimmune neonatal neutropenia seems to be lower than 0.1%. PMID- 1284758 TI - [Neonatal isoimmune thrombocytopenia by anti-GP IIb/IIIa]. AB - Neonatal alloimmune thrombocytopenic purpura is caused by maternal platelet specific alloantibodies which react on fetal platelets with the corresponding antigen. We describe a 30-year-old female patient with type I Glanzmann thrombasthenia who developed an isoantibody against the platelet GP IIb/IIIa complex before or during pregnancy. The platelet count in the male newborn was 35 x 10(9)/l, but there were no signs of cerebral hemorrhage. Following infusion of 2 g/day i.v. IgG on 3 consecutive days, platelet counts rose to normal values. An isoantibody reacting with the GP IIb/IIIa complex of all platelet donors tested was found in the maternal serum using the MAIPA assay. Thus, immune-mediated neonatal thrombocytopenia may be caused by platelet isoantibodies against GP IIb/IIIa as well as by platelet-specific alloantibodies and by maternal autoantibodies. PMID- 1284759 TI - [Effects of an infusion pump with peristaltic mechanism of action on various blood components in vitro]. AB - Apart from a slight hemolysis at very low flow rates, the peristaltic infusion pump IVAC 560 has no harmful effects on blood components such as packed red cells, whole blood, platelet concentrates and fresh frozen plasma. So it may be a convenient option to perform volume processed transfusions. PMID- 1284760 TI - [Decreasing the risk of post-transfusion non-A, non-B hepatitis by anti-HCV screening]. AB - In May 1990 a specific enzyme immunoassay (EIA) for NANBH was developed by recombinant DNA technology which detects antibodies to a virus called hepatitis C virus (HCV). The anti-HCV EIA was manufactured by Ortho Diagnostic Systems with recombinant antigens from Chiron Corp. based on extraction from high infectious titer chimpanzee plasma RNA after transcription into cDNA. We tested the anti-HCV prevalence of blood donors and hemodialysis patients. The anti-HCV prevalence with the first generation test was 0.52% (Ortho), 0.87% (Abbott) in blood donors and 4.16% in hemodialysis patients. The second generation anti-HCV test (Abbott) with improved sensitivity and specificity comprises 0.25% repeated anti-HCV positive blood donors and 8.2% anti-HCV-positive hemodialysis patients. PMID- 1284761 TI - Biocompatibility of synthetic oxygen carriers and fluorosurfactants. AB - A system for testing the biocompatibility of synthetic oxygen carriers is described including tests of hemolysis, complement activation and proliferation of cell lines or lymphocytes. Of 17 surfactants tested in this system, 6 were compatible in all tests while the other compounds showed individually differing patterns of incompatibility. We conclude that, in order to conduct a meaningful screening, a series of different assays has to be applied. Addition to our system of further assays covering cytokine induction and phagocytosis should be attempted. PMID- 1284762 TI - [Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes]. AB - In a retrospective analysis we assessed the data of 46 patients with myelodysplastic syndromes (MDS), who had received more than 50 blood transfusions during the course of disease. The number of units given ranged from 50 to 155 (mean 79). 20 patients (RA n = 4, RARS n = 12, RAEB n = 1, RAEB/T n = 2, CMML n = 1), followed up between 8 and 108 months (mean survival time 39.4 months), developed a secondary hemochromatosis. More than 40% of the patients showed signs of heart failure, in some cases accompanied by cardiac arrhythmias. 11 patients also suffered from hepatopathy and 5 developed diabetes mellitus. Secondary hemochromatosis was particularly common in patients with RARS. Refractory congestive heart failure secondary to hemochromatosis was the cause of death in 14 patients, whereas none died from hepatic insufficiency. We conclude that the risk of secondary hemochromatosis should not be neglected in polytransfused patients with MDS. In some cases, particularly those with favorable prognostic features of MDS, it may shorten life expectancy. The availability of a new oral iron chelator (1,2-dimethyl-3-hydroxypyrid-4-one or L1) offers a promising and practicable approach to prevent this complication. PMID- 1284763 TI - [Prevalence of lupus anticoagulant, autoimmune hemolysis, thrombocytopenia and disorders of platelet function in unselected patients with SLE]. AB - Prevalence of lupus anticoagulant (LA) in patients with systemic lupus erythematosus (SLE) and clinical manifestations vary widely between different clinical series. We investigated the relation between LA, autoimmune hemolytic anemia (AIHA), thrombocytopenia and platelet dysfunction in 80 unselected patients with SLE. AIHA was found in 6 patients (7.5%) and thrombocytopenia in 10 patients (12.5%), which was not related to platelet aggregation abnormalities. Compared to controls, patients with SLE showed significantly prolonged aPTT and kaolin clotting time (KCT), but platelet aggregation induced by both collagen and thrombin was not impaired. LA activity as defined by Rosner et al. (index for LA/ICA) was found in 15 patients (18.9%). Only 7 of these patients showed a positive platelet neutralization test (Triplett) and 9a positive tissue thromboplastin inhibition test (Schleider). In our SLE patients 23.7% have suffered from at least one thrombotic complication. In patients with LA activity thromboembolic complications were increased (p < 0.05). Thrombocytopenia was found in 6% of LA-negative but in 20% of LA-positive patients. PMID- 1284764 TI - [Electronic data processing-assisted serial automation of current methods in blood group serology]. AB - The introduction of special centrifugable racks with a transparent bottom into the conventional typing of blood groups in glass tubes facilitates the simultaneous work on and reading of a maximum of 32 complete ABO, Rhesus and Kell typings in one series. As a result of the facts that it is unnecessary to label the individual tubes and that the pipetting of serum and erythrocyte suspensions is done automatically and through the unmistakable classification of the samples by means of bar-coding, the manual work is reduced to about 50%. This modified typing method combines the advantages of the conventional typing method in glass tubes with the advantages of an efficient microplate technique. There is no qualitative loss in the implementation and reading of the analysis. PMID- 1284765 TI - Detection of antibodies to hepatitis C virus in blood donors and their relationship to surrogate markers. AB - Stored serum samples from 7,179 nonselected blood donors were tested for anti-HCV using Ortho EIA first generation. Results were compared to data acquired by anti HBc testing and ALT levels found in routine testing. 24 donors (0.33%) were repeatedly reactive with Ortho HCV EIA, 230 (3.20%) were anti-HBc-positive and 138 (1.92%) had raised ALT levels > or = 36 IU/l. A low correlation was found between HCV antibody screening with EIA and surrogate testing. When tested in addition with the Abbott HCV EIA, 20 of the 24 Ortho EIA-positive subjects showed a positive reaction. In the Abbott neutralization test 13 of these 20 (65%) were reactive. 8 (33.33%) of the 24 Ortho-EIA-positive donors were positive in the two antigen-RIBA (first generation), 8 were indeterminate and 8 were nonreactive. The neutralization test and the RIBA can be used as supplementary tests fo further analyze HCV-EIA-positive specimens. PMID- 1284766 TI - [Sex and age specific GPT limit values in blood donors]. AB - Excluding blood donations with elevated serum ALT from transfusion is only justified under the assumption that these more frequently transmit unrecognized hepatitis infections. The distribution of such infections in the donor population (with respect to age and sex) should be similar to that of hepatitis B and C, respectively. The prevalence of the latter two infections among our blood donors is the same in both sexes. The exclusion rate, however, is 3-4 times higher for men if equal ALT limits are applied. We therefore determined which ALT limits would give equal exclusion rates for donations of male and female blood donors in order to balance the risk of unrecognized hepatitis in blood donations from the two sex groups. In a second step, we also took each donor's age group into account and determined individual ALT limits for different age and sex groups. PMID- 1284767 TI - [Distribution of the incidence of SGPT activity in blood donors]. AB - Predonation SGPT (ALT) testing was performed in 5,706 blood donors (3,944 male, 1,762 female) with the Reflotron system. The values of SGPT activities (IU/l; 25 degrees C) are not normally distributed, whereas the log10 SGPT distribution is largely Gaussian (the arithmetic mean log10 +/- SD for female donors is 0.98 +/- 0.14 and for male donors 1.08 +/- 0.16, the antilog of the mean log10 9.5 and 12.1 IU/l, respectively). In the following the impact of SGPT testing at various exclusion levels on the percentage of deferred donors is shown: (1) female: cutoff level > 18.0 IU/l (mean log10 +2.0 SD) 2.8%, > 19.5 IU/l (+2.25 SD) 2.1%, > 21.1 IU/l (+2.5 SD) 1.8% and > 24.8 IU/l (+3.0 SD) 1.2% deferment. (2) male: cutoff level > 25.2 IU/l (mean log10 +2.0 SD) 2.7%, > 27.6 IU/l (+2.25 SD) 2.3%, > 30.3 IU/l (+2.5 SD) 1.4% and > 36.4 IU/l (+3.0 SD) 0.8% deferment. Using the current cutoff value of > 45 IU/l (according to German regulations, 1987) only 0.2% female (with SGPT > mean log10 +4.5 SD) and 0.3% male (with SGPT > mean log10 +3.5 SD) donors would be excluded. These findings demonstrate that different SGPT exclusion levels for men and women are necessary and that the current cutoff value of > 45 IU/l does not exclude donors who should better be rejected. PMID- 1284768 TI - The discovery of the NANB hepatitis virus by gene technology. PMID- 1284769 TI - [Etiology of increased SGPT activity in blood donors]. AB - From all blood donors screened within a given period of 6 months for SGPT (ALT) immediately before donation, 166 (141 male, 25 female) were found to have SGPT activities above our cutoff value of > 28 IU/l (25 degrees C). In order to define the characteristics of these blood donors they were asked for detailed medical history followed by a thorough physical examination and further serologic and biochemical testing. Factors associated with elevated SGPT activity included daily alcohol consumption (82 donors), infections associated with abnormal DCs (23), therapy with hepatotoxic drugs (8), infections that had been treated with antibiotics (6), strenuous physical exercises (5), body building supported by anabolics (2), acute HBV infection (1), acute HCV infection (1), alcohol/drug abuse and positive test for anti-HCV antibodies (1), anti-CMV positivity with absolute and relative lymphocytosis (1). In 36 cases factors that could have been associated with an increased SGPT activity were not verified. A critical valuation of the presently accepted cutoff value of 45 IU/l (25 degrees C) is given. PMID- 1284770 TI - [High precision, reproducibility and practical application of modified alanine aminotransferase determination with the microtiter plate]. AB - In order to improve the alanine aminotransferase (ALT) assay by using microtiter plates, a new 96-channel multiple syringe of high precision and incubation chambers with precise regulation of the temperature operated by computer were developed. In accordance with the recommendation of the German Society of Clinical Chemistry for the optimized standard method, the ALT assay was modified for the procedure at 25 degrees C. The modification was comparable with the best conventional methods which, however, are very time-consuming. The ALT assay has the advantages of the microtiter plate, e.g., secure sample identification, on line documentation and reduction of costs and time for the analysis. PMID- 1284771 TI - [Kinetic measurement of GPT with the microtiter plate]. AB - Experiences with a kinetic method for measurement of SGPT in microtiter plate using an automatic sample processing device and Medusa software (Biotest) were evaluated. The correlation coefficient in parallel assessment of samples in a clinical routine laboratory was found to be 0.935 (p < 0.0001). The correlation coefficient comparing the internal standard dilution with actual recordings was found to be 0.999 (p < 0.0001). Automated screening of SGPT in microtiter plates seems thus to be reliable as well as feasible in blood bank routine. PMID- 1284772 TI - [Diagnosis of the presence of SGPT in blood donors]. AB - Presampling determination for hemoglobin has been pursued for a long time, but now it is becoming possible to examine further parameters such as SGPT (ALT). The SGPT predonation testing is best performed with the Reflotron system (Fa. Boehringer Mannheim) since whole blood samples drawn into capillary tube can be used. Between 1985 and 1988 1.35-1.75% of an average of 22,000 whole blood donations were found to have SGPT levels above the accepted cutoff (> 30 IU/l, 25 degrees C). The cost per test using the UV kinetics and the overall expenses of unusable collections were compared with the cost of SGPT predonation testing. An average of DM 20,000.-per year has been saved. Therefore prescreening of SGPT in blood banking is a highly cost-effective approach. PMID- 1284773 TI - [ALAT (GPT) screening with the microtitration plate]. AB - Sera of donors with values above the controls have been retested by the optimized standard method at 37 degrees C. 103 of 420 sera which had to be retested also showed elevated ALT in the optimized standard method. Therefore we conclude that the ALT microplate test used is suitable as screening test in blood donors. PMID- 1284774 TI - Recombinant antigens in viral diagnosis. AB - DNA fragments coding for a variety of different viral antigens have been cloned and expressed in Escherichia coli. Selected purified recombinant antigens were used for detection of specific antibodies by means of the ELISA technique. This approach has been used for the development of four different ELISAs for the detection of HIV- and EBV-specific antibodies. PMID- 1284776 TI - Treponema pallidum membrane protein A ELISA: a new test for screening and diagnosis of syphilis. AB - A new ELISA test system for screening antibodies directed against Treponema pallidum is presented. The ELISA is based on a recombinant DNA-derived T. pallidum membrane protein A (TmpA). It makes the production of the kit easier as it abandons the necessity to culture T. pallidum in living animals. The specificity and sensitivity of the ELISA are comparable with those of the TPHA and FTA-ABS. The test gives only a positive result when there are antibodies against the TmpA antigen and, therefore, it gives in screening (e.g. blood donors) no false-positive reaction in persons who, due to an old well-treated infection, have a so-called serological scar. As these donors are noninfective, they should be concerned as negative in syphilis screening. PMID- 1284775 TI - [Follow-up of blood donors with indeterminate reaction to anti-HIV 1/2 EIA or isolated detection of antibodies to HIV-1 core antigens (anti-p24)]. AB - Over a period of 20 months we identified 10 voluntary blood donors with indeterminate reactions in anti-HIV 1/2 EIA tests. Western blot (WB) patterns of 6 of these 10 donors showed isolated core antibodies (anti-p24), in 4 cases WB patterns were negative. After a median follow-up period of 58 weeks (range 12-93) we have not seen a case of typical seroconversion. PMID- 1284777 TI - [Prevalence of Borrelia burgdorferi antibodies in Hamburg blood donors]. AB - One thousand regular blood donors of the Department of Transfusion Medicine at the University Hospital in Hamburg were screened for antibodies against the Lyme disease spirochete, B. burgdorferi. 7.2% were initially reactive in the enzyme immunoassay, 37.5% of which were confirmed by immunoblot. The seroprevalence of anti-B. burgdorferi antibodies thus is 2.7% in Hamburg blood donors. 25 of 27 positive donors received a physical exam, which did not reveal any symptoms of acute or chronic Lyme disease. 24 of these 25 donors were tested for B. burgdorferi-specific DNA in urine by polymerase chain reaction, which came out negative in all cases. Introduction of B. burgdorferi antibody screening is not regarded an effective means to prevent transfusion-transmitted Lyme disease. PMID- 1284778 TI - [Infections with Borrelia burgdorferi in Wurzburg blood donors: antibody prevalence, clinical aspects and pathogen detection in antibody positive donors]. AB - The prevalence of antibodies against Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, was determined in a group of blood donors from the Wurzburg area (Southern Germany). 26 of 472 donors (5.5%) tested positive in a hemagglutination test. When performing immunoblots only 13 donors (2.7%) gave rise to B. burgdorferi-specific antibodies. 9 of them were examined in more detail by anamnesis, physical examination, determination of inflammation parameters of the blood and polymerase chain reaction (PCR) analysis of urine. All persons were asymptomatic for Lyme borreliosis. One of 4, who remembered a tick bite, actually had suffered from an erythema migrans 5 years ago. Another one had been affected by fever, headaches and pains in the limbs, arthralgia and motoric disorder in both hands 6 months before examination. Analysis of the blood did not provide any evidence of an acute infection. In the urine of 2 donors we detected B. burgdorferi-specific DNA by PCR. No seroconversion due to blood transfusion could be observed, when 9 recipients of blood products provided by the 13 seropositive donors were serologically reexamined. PCR analysis of urine samples of 5 recipients was also negative. PMID- 1284780 TI - Physicochemical characterization of Escherichia coli. A comparison with gram positive bacteria. AB - Eight Escherichia coli strains were characterized by determining their adhesion to xylene, surface free energy, zeta potential, relative surface charge, and their chemical composition. The latter was done by applying X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (IR). No relationship between the adhesion to xylene and the water contact angles of these strains was found. Three strains had significantly lower surface free energies than the other strains. Surface free energies were either obtained from polar and dispersion parts or from Lifshitz-van der Waals and acid/base parts of the surface free energy. A correlation (r = 0.97) between the polar parts and the electron-donor contributions to the acid/base part of the surface free energy was found. The zeta potentials of all strains, measured as a function of pH (2-11), were negative. Depending on the zeta potential as a function of pH, three groups were recognized among the strains tested. A relationship (r = 0.84) was found between the acid/base component of the surface free energy and the zeta potential measured at pH = 7.4. There was no correlation between results of XPS and IR studies. Data from the literature of XPS and IR studies of the gram-positive staphylococci and streptococci were compared with data from the gram-negative E. coli used in this study. It appeared that in these three groups of bacteria, the polysaccharide content detected by IR corresponded well with the oxygen-to-carbon ratio detected by XPS. PMID- 1284779 TI - Effect of a phorbol ester on basic surface properties of trichomonads. AB - The effect of nanomolar concentrations of 12-O-tetradecanoilphorbol-13-acetate (TPA) on the cell surface of the urogenital parasitic protozoa Trichomonas vaginalis and Tritrichomonas foetus was evaluated by means of measurements of the parasites' surface tension, electrokinesis, lectin agglutination tests, and adhesion to inert substrates. TPA-treated parasites had their adhesion increased to both plastic and glass substrates. This was accompanied by increases in the parasites' net negative surface charge and also by changes in their surface tension. The lectin agglutination assays suggest that the increase in surface negativeness may be related in some extent to alterations in the oligosaccharide composition. Successive treatment of the microorganisms with TPA and sphingosine, a well-known competitive inhibitor of the phorbol ester active site, depressed the tendency of trichomonads to exhibit a phenotype of activated cells. PMID- 1284781 TI - Evidence for lymphocyte chemotaxis toward monocytes during PHA-induced aggregation in vitro. AB - An important, early phenomenon during the development of immune cell interactions in vitro is the formation of multicellular aggregates. We have developed a quantitative assay to determine the kinetics of multicellular aggregate formation within a heterotypic population of cells on a flat surface. This assay follows the time rate of change in the value of an aggregation index for cells in undisturbed culture. For an initial, well-separated population of cells, the index is a minimum and remains at this value if the cells do not move and interact. By contrast, for conditions that promote active cell movement followed by interaction, the index value increases with time. The index, which reflects cells' relative spatial distributions, is an "indirect enumeration" of the number of cells within aggregates as a function of time. We used this index to follow the aggregative behavior of a population of freshly isolated human peripheral lymphocytes and monocytes. Previous studies have shown that monocytes are centrally located within aggregates and that lymphocytes move to surround monocytes. In order to test if lymphocyte movements are random or directed prior to interactions with monocytes, we formulated a simple model to describe changes in the expected number of cells in an "idealized aggregate" as a function of time. A comparison of the model curves with curves generated from the changes in the aggregation index shows that the best fit derives from a model that involves directed movement of lymphocytes toward monocytes. These results suggest that monocytes produce a chemoattracting agent for lymphocytes for these experimental conditions. PMID- 1284782 TI - Characterization of eukaryotic cell surfaces prior to and after serum protein adsorption by X-ray photoelectron spectroscopy. Fibroblasts, HELA epithelial, and smooth muscle cells. AB - Elemental surface concentration ratios N/C,O/C, and P/C of fibroblasts, HELA epithelial cells, and smooth muscle cells, prior to and after washing in the absence or presence of serum proteins, were determined by X-ray photoelectron spectroscopy. Cell surfaces appeared to adsorb hardly any serum proteins, and the relatively high P/C, as compared to N/C and O/C, elemental surface concentration ratio indicated that the cell surfaces consisted mainly of the phospholipid bilayer, with little or no proteins present. The lack of adsorption of serum proteins to the cell surfaces seems at odds with the common notion that cells require adhesive proteins in order to adhere and spread. However, the adsorption behavior of cellularly produced proteins may be completely different, particularly since they seem to be able to displace adsorbed serum proteins from biomaterials surfaces. Interestingly, only HELA epithelial cells (a tumor cell line) appeared to adsorb a very small amount of proteins. PMID- 1284783 TI - Surface charge and hydrophobicity of wild and mutant Crithidia fasciculata. AB - Surface charge of wild-type Crithidia fasciculata and three drug-resistant mutants (TR3, TFRR1, and FUR11) was studied by direct zeta-potential determination and ultrastructural cytochemistry. Surface tension was also investigated by measurements of the advancing contact angle formed by the protozoa monolayers with drops of liquids of different polarities. The individual zeta potential varies markedly among the C. fasciculata cells. The wild and FUR11 mutant strains displayed lower negative surface charge (-12.5 and -9.5 mV, respectively) as compared with the TR3 (-14.8 mV) and TFRR1 (-14.7 mV) mutant strains. Binding of cationized ferritin (CF) was observed at the cell surface of wild and mutant strains of C. fasciculata. Neuraminidase treatment reduced the negative surface charge in the TFRR1 and TR3 mutants in about 37 and 29%, respectively, whereas no significant change was observed with the wild and FUR11 mutant strains. These findings suggest that sialic acid residues are the major anionogenic groups on the surface of C. fasciculata. The density of sialic acid residues per cell in wild and mutant strains of C. fasciculata falls in a range of 1.4 x 10(4) to 3.6 x 10(4). Marked differences of hydrophobicity were also observed. For example, the TFRR1, FUR11, and TR3 drug-resistant mutant strains showed higher contact angle values (55.4, 54.2, and 49.3, respectively) than the wild-type (35.6), as assessed by alpha-bromonaphtalene. PMID- 1284784 TI - Ion flow through biomembranes. Physical theory explains its high sensitivity. AB - Numerous biomembranes exhibit a sensitivity to changes in electrical potential greater than predicted as possible from the classical application of the Boltzmann relation, a phenomenon which has long defied explanation, the actual sensitivity of some Na+ channels being many times greater than the classical limit. This paper explains, using a minimum of mathematics, how the very rapid gating effect of adsorbed Ca2+ (or other impermeable divalent cations) can directly affect the conductance of channels, and thus interact with the electric field within the channel to produce a change in the potential across the channel's gate much greater than the change in the membrane potential, with a corresponding change in the fraction of open conformational gates and change in conductance. These results are not in conflict with the Boltzmann relation, the necessary energy being made available from the total potential difference across the membrane by a long unrecognized stochastic process; the full mathematical theory is given in cited references. PMID- 1284785 TI - Depth profiling of the elemental surface composition of the oral microorganism S. salivarius HB and fibrillar mutants by X-ray photoelectron spectroscopy. AB - X-ray photoelectron spectroscopy (XPS) on microbial cell surfaces requires freeze drying of cells, and as a result, the cell surface appendages flatten out on the cell surface and form a collapsed fibrillar mass. At present, it is unclear how the density, length and composition of these fibrils influence the elemental surface composition as probed by XPS. The sampling depth of XPS can be varied by changing the electron take-off angle. In this article, we made a depth profiling of the collapsed fibrillar mass of Streptococcus salivarius HB and fibril deficient mutants by angle-dependent XPS. Methylamine tungstate negative staining and ruthenium red staining followed by sectioning revealed distinct classes of fibrils with various lengths on each of the strains. Interpretation of the angle dependence of the oxygen/carbon (O/C) and phosphorus/carbon (P/C) surface concentration ratios of these strains was difficult. However, the angle dependence of the nitrogen/carbon (N/C) surface concentration ratio could be fully interpreted: N/C did not vary with sampling depth on a bald strain, S. salivarius HBC12 and on S. salivarius HB7, a strain with a dense array of fibrils of uniform length. N/C decreased with sampling depth in case of a sparsely fibrillated strain, S. salivarius HBV51 and eventually reached the value observed for the bald strain, HBC12. A high N/C at small sampling depth was observed for S. salivarius HB with protruding, protein rich fibrils. We conclude that elemental depth profiling of microbial cell surfaces by XPS can be interpreted to coincide with structural and biochemical information on the cell surface as obtained by electron microscopy and can therefore be considered as a useful technique to study structural features of cell surfaces in combination with electron microscopy. PMID- 1284787 TI - Studies on the quantification of proteoglycans by the dimethylmethylene blue dye binding method. Specificity, quantitation in synovial lavage fluid, and automation. AB - The dimethylmethylene blue (DMMB) dye-binding technique is widely used for the quantification of sulfated glycosaminoglycans (sGAG) and proteoglycans. We conducted further studies on this technique in our laboratory and found that concentrations of DNA and RNA in excess of 20 micrograms/ml interfered negatively with the detection of sGAGs; interference was eliminated by using DNase and RNase. Hyaluronan at 40 micrograms per ml did not interfere with the detection of sGAG. However, because of the higher concentrations of hyaluronan in synovial lavage fluid, it was necessary to treat this fluid with Streptomyces hyaluronidase in order to quantify sGAG. The DMMB assay was automated with a laboratory work station and compared to the standard method. PMID- 1284786 TI - Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor. AB - Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/ 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected. PMID- 1284788 TI - Evaluation of combined assays of serum ferritin, alpha-1-antitrypsin and alpha fetoprotein in liver cancer. AB - Serum ferritin (SF), alpha-1-antitrypsin (AAT) and alpha-fetoprotein (AFP) were examined preoperatively in 66 patients with intrahepatic space-occupied lesions revealed by B-real time ultrasonography. Elevated SF levels (> 300 micrograms/L in males and > 180 micrograms/L in females), AAT levels (4.2 g/L), and AFP levels (> 20 micrograms/L) were shown in 84%, 71% and 66% respectively of 55 patients with liver cancer. Combined analysis indicates that if all the three tests are negative, liver cancer can be essentially excluded; and positive AFP can rule out hepatic hemangioma. So combined assays of SF, AAT and AFP are valuable in the diagnosis and differential diagnosis of liver cancer. PMID- 1284789 TI - Rapid immunostaining of live nerve for identification of sensory and motor fasciculi. AB - Six New Zealand white rabbits were anesthetized with pentobarbital, and sciatic nerves were exposed and cut at the mid thigh. Both proximal and distal ends were incubated directly with Blue-SAb in a micropipe of 5 mm diameter covering the nerve trunk ends for 30 minutes at room temperature. After removal of the micropipe, the nerve ends were washed with physiological saline. Blue-stained fasciculi, i.e., sensory fasciculi were seen among unstained ones under the operating microscope. This method requires no histological sections. Neural cells of the spinal cord and ganglion were cultured in RPM11640 medium containing Bright Blue. The growth and metabolism of the neural cells were tested by MTT assay and their morphology was observed. Statistical difference between the experiment and control groups was determined, indicating that Bright Blue had no effect on the neural cells and their repairing power. This rapid immunostaining technique offers a good approach for the identification and accurate coaptation of sensory fasciculi in peripheral nerve repair. PMID- 1284790 TI - [An immunohistochemical study of occult micrometastases in regional lymph nodes of patients with stage I non-small cell lung carcinoma]. AB - 739 regional lymph nodes from 94 patients with stage I non-small cell lung carcinoma (NSCLC) were studied by immunohistochemistry. These lymph nodes, contained no metastasis as assessed by conventional histopathology, were recut. A series consecutive sections from the original blocks were immunostained with polyclonal and monoclonal antibodies to keratins, carcinoembryonic antigen (CEA) and human milk fat globulin membrane antigen (HMFG-2). Single tumor cells or small clusters of tumor cells, not visible on routine examination, were readily detected. The actual number of lymph nodes that contained occult tumor cells was 123 (16.6%) from 53 patients (56.4%). The majority of 102 immunostaining positive nodes were distributed in the hilar (29%) and peribronchial (25%) regions. Our data indicate that: 1. a series consecutive sections and immunohistochemistry may greatly increase the diagnostic yield of occult micrometastases in lymph nodes. 2. the high incidence of occult metastases in NSCLC may be of importance in relation to their rapid dissemination and high death rate. 3. the high frequency of occult nodal metastases in NSCLC raises questions in regard to our presently used criteria for staging, prognosis and treatment of ostensibly stage I disease. 4. perhaps resections of hilar and peribronchial lymph nodes will have an important clinical significance in prevention of wide dissemination of tumor cells. PMID- 1284791 TI - [The production and identification of partial serogroup--specific monoclonal antibodies against leptospires hebdomadis serogroup]. AB - Hebdomadis is one of the major serogroups found in China. In Sichuan, this serogroup appears to have a close relationship with local outbreak of leptospirosis. BALB/c mice were immunized intrasplenically with outer envelope of serogroup Hendomadis serovar hebdomadis strain 245. Spleen cells were fused with SP2/0 myeloma cells, two monoclonal antibodies Af2 and Bb2 were produced by hybridoma technique. McAb Af2 and McAb Bb2 were identified to be IgG1 and IgG3 by immunodiffusion respectively. Specificities of these two McAbs were determined by MAT; both reacted to 8 serovars (hebdomadis, nona, kambale, kremastos, worsfoldi, jules, maruborincana) of Hebdomadis serogroup. The agglutination titres of McAb Af2 and McAb Bb2 were 1:640-1:2,500,000 and 1:320-1:2,500,000, respectively. The two McAbs did not agglutinate with serovar kabura of Hebdomadis serogroup, they did not agglutinate with 11 serovars of Sejroe serogroup, 4 serovars of Mini serogroup, 18 representive serovars of L. interrogans in 18 serogroups, L. biflexa strain Patoc I and Leptonema illini. So it was found that McAb Af2 and McAb Bb2 showed partial serogroup specificity for Hebdomadis by agglutination. PMID- 1284792 TI - [Radioimmunoassay of serum and CSF myelin basic protein and its application to patients with acute cerebrovascular accident]. AB - Myelin basic protein (MBP) was measured in the serum and CSF of patients with acute cerebrovascular disease (CVD, 34 cases), demyelinating disorders (DMD, 30 cases) and other neurological diseases (OND, 26 cases) by using a double antibody radioimmunoassay (RIA). Patients with acute CVD had a mean serum MBP concentration and positivity rate much higher than those with DMD and OND. The differences were significant (P < 0.05). In CSF, MBP levels in patients with acute CVD and patients with DMD were significantly greater than those in OND patients (P < 0.05). The results also show that there was a linear relationship between the CSF MBP levels and the serum MBP levels in patients with acute CVD (r = 0.72, P < 0.01), but no such relationship in patients with DMD and OND. The amount of serum MBP was also significantly correlated to the severity of acute CVD, to the level of consciousness disorder and limb paralysis, and to the extent and site of the cerebral lesion at CT-scan (P < 0.05). This study shows that the measurement of brain specific MBP in serum as a marker of cerebral damage may have clinical value in the diagnosis and prognosis of patients with CVD. PMID- 1284793 TI - [Alpha 2 megaloglobulin inhibits the activation of rabbit platelet by Chinese Agkistrodon acutus venom]. AB - An in vitro study of alpha 2-mengaloglobulin (alpha 2MG) in the inhibition of the activation of washed rabbit platelet by Chinese Agkistrodon acutus venom (CAAV) was reported. Results showed that CAAV induced aggregation rate of washed rabbit platelet was positively related to the CAAV concentration, and the maximal aggregation rate was 43.8 +/- 9.9% at the concentration of 100 micrograms/ml. Meanwhile the release of serotonin (5-HT) and platelet factor 4(PF4) from the platelet reached maximum at the CAAV concentrations of 0.81 +/- 0.07 microgram/ml and 39.08 +/- 2.78%, respectively. Platelet aggregation and the release of 5-HT and PF4 induced by CAAV could be inhibited by the addition of 0.25% alpha 2 MG into the platelets both 1 minute before and 1 minute after the addition of CAAV. When alpha 2 MG was added to the platelets 1 minute prior to the addition of CAAV, the platelet aggregation and the ultrastructural changes which could be induced by CAAV were not observed, and the morphology of the rabbit platelets was the same as that of the normal counterparts. PMID- 1284794 TI - The mossy fiber terminals in the hippocampal formation of Callithrix jacchus: comparative and evolutionary considerations. AB - The distribution of mossy fiber terminals in the regio inferior of the hippocampus of Callithrix jacchus was studied by means of Timm's method. The topographic distribution of Timm-positive zones in the hilus, in the suprapyramidal and intrapyramidal areas of the CA3 subfield is described. A Timm positive reaction in intragranular strips and supragranular zones, the presence of Timm-negative zones in the infragranular border of the fascia dentata were found in this species. A comparison between mossy fiber distribution in Callithrix jacchus and that in human was carried out in an attempt to identify interspecies differences in the mossy fiber system in the hippocampus of primates. The hypothesis of a possible functional relevance of the supra- and intrapyramidal mossy fiber terminals on the control of hippocampal pyramidal neurons is expressed. PMID- 1284795 TI - Study of neovascularization of the jejunal graft--a new animal model. AB - The development of a new rabbit model for study of neovascularization of the jejunal graft is described. The relationship between stripping of the serosal membrane and the speed of the neovascularization process was analyzed. The results demonstrate that the visceral peritoneum acts like a physical barrier, retarding the formation of the new nutrient blood supply from recipient bed to the jejunal graft. PMID- 1284796 TI - Functional abnormalities of circulating natural killer cell subpopulations in patients with dilated cardiomyopathy. AB - We investigated abnormalities in natural killer (NK) cells in the myocardium and circulating blood of 38 patients with idiopathic dilated cardiomyopathy (DCM), 18 patients with hypertrophic cardiomyopathy, 8 patients with primary amyloidosis, and 12 age-matched normal control subjects. Immunohistochemical staining of myocardial biopsies revealed a significantly greater number of CD57-positive NK cells in patients with DCM than that in controls (3.7 +/- 2.7 v.s. 1.9 +/- 1.6, p < 0.05). The New York Heart Association functional class, left ventricular ejection fraction, myocardial fiber diameter, and interstitial fibrosis volume fraction did not differ significantly between the DCM patients who died within five years of diagnosis and the 31 surviving DCM patients. However, there were significantly fewer CD57-positive NK cells in patients who died than in surviving patients (p < 0.05). There were no significant differences in the peripheral NK cell activity or the number of NK subset cells between the 16 patients with DCM (n = 16) and the 12 age-matched normal controls. In normal controls, the number of some NK cell subpopulations (CD16+, CD57+, CD16+ CD57+, and CD8+ CD57+ cells) were positively correlated with NK cell activity. In patients with DCM, there was no correlation between the number of NK cell subpopulations and NK cell activity. Our findings indicate that functional abnormalities exist in NK cell subpopulations in patients with DCM, and that these abnormalities may be related to the pathogenesis of DCM. PMID- 1284797 TI - Impact of serum concentration of the medium and fasting on the imprintability of the insulin receptors of Chang liver cells. AB - When the cells of the Chang cell line came into interaction with a hormone (insulin) an imprinting-like phenomenon took place. The binding capacity of the receptors strengthened and this feature was transmitted to the descendant generations. The quality of the nutrient medium influenced the development of imprinting, when the cells were maintained in a medium containing 2% serum it was more difficult to evoke imprinting than in case the cells were kept in a medium containing 10% serum. If the cells were cultured kept in Tyrode (physiological) solution for 24 hours the possibility to evoke imprinting was lost. Difference could be observed between the behaviour of receptors in nuclear membrane and that of receptors in the plasma membrane; i.e. changes were more dynamic in the plasma membrane. PMID- 1284798 TI - Intravenous urography pre-prostatectomy: an evaluation of its use. AB - The pre-operative intravenous urograms of 120 consecutive patients who had prostatectomy for benign prostatic hypertrophy (BPH) were studied. Of these, seventy-eight patients (65%) had normal intravenous urograms (IVU) while 42 patients had abnormal IVU. In this study serum creatinine above 2.0mg% and Blood urea above 35mg% proved valuable indices for possible selection of patients with BPH likely to show significant obstructive disease on IVU. This is not only cost saving, but also reduces unnecessary radiation to the patients. PMID- 1284799 TI - [The influence of paraquat on cell cycle--analysis of cell kinetics using DNA/BrdU staining]. AB - We examined the in vitro and in vivo effects of paraquat on the cell cycle. After we exposed paraquat to the cultured cell (MDCK), we examined cell kinetics by flow cytometry with BrdU-PI double staining. And we administered paraquat intravenously to the rats, we collected and separated rat's liver and pulmonary cells, and we examined the cell kinetics by same method. Consequently our study found that the cells in the S-phase were noted to be abundant, and we suggested that paraquat apparently arrested the cell cycle at S time, and that DNA damage was importance in the mechanism of paraquat toxicity. PMID- 1284800 TI - Presence and significance of some antibodies/autoantibodies in patients with acute myocardial infarction and idiopathic dilated cardiomyopathy. AB - By using ELISA technique we determined the anti-myosin, actin, collagen type I and IV, cholesterol and phosphotyrosine proteins antibodies in sera from patients with acute myocardial infarction and idiopathic dilated cardiomyopathy. In idiopathic dilated cardiomyopathy we found a significant increase in five out of six types of antibodies tested. The patients with acute myocardial infarction reveal high levels of anti-myosin antibodies only. Our results suggest that some of the autoantibodies studied by us have a prognostic value and could be involved in maintaining cardiac dysfunctions. PMID- 1284801 TI - [The regeneration of hematopoietic and connective tissues]. AB - The data are summarized on comparative investigations by the author and co workers concerning regenerative process in hemopoietic and connective tissues of representatives of molluscs, cyclostomes, fishes and mammals. In gastropods, a regeneration stimulus strikingly increases the volume of amebocyte reproduction foci in the pericardium (primitive organ of hemopoiesis), accelerates the amebocyte yield into the peripheral blood and induces the appearance of DNA synthesizing cells in the latter. The stimulation of precursor cell reproduction in hemopoietic organs and the acceleration of their maturation and yield into the peripheral blood are common processes in the regeneration response for hemopoietic systems of mammals, fishes and cyclostomes. In contrast to fishes and cyclostomes, adult mammals show the absence of dividing (DNA-synthesizing) cells and mature segmentonuclear granulocytes demonstrate neither RNA nor protein synthesis. In all forms studied, the stromal type cells of hemopoietic nature (fibroblast-like, fixed macrophages, etc.) are a constant and continuously renewed component of connective tissue and play a considerable role in its regeneration. PMID- 1284802 TI - Inhibition of choline efflux results in enhanced acetylcholine synthesis and release in the guinea-pig corticocerebral synaptosomes. AB - Synthesis and release of [3H]acetylcholine ([3H]ACh) were measured in synaptosomes from the guinea pig cerebral cortex after preloading with [3H]choline ([3H]Ch). We demonstrate here that inhibition of choline (Ch) efflux results in an increase in acetylcholine (ACh) synthesis and release. Our findings are as follows: (1) inhibition of [3H]Ch efflux by hemicholinium-3 (HC-3) (100 microM), increased the levels of both the released (116% of control) and the residing (115% of control) [3H]ACh. (2) The muscarinic agonist, McN-A-343 (100 microM), which was previously shown to inhibit Ch efflux, also increased the released (121% of control) and the residing (109% of control) [3H]ACh. (3) Omission of Na+ ions (which are required for Ch transport) from the incubation medium had similar effects to those observed with McN-A-343 and HC-3. These results suggest inverse relationships between Ch efflux on one hand, and ACh synthesis and release on the other hand. (4) Depolarization with 50 mM K+, or with the K+ channel blocker, 4-aminopyridine (100 microM), also increased the total level of [3H]ACh (113 and 107% of nondepolarized synaptosomes, respectively). However, whereas conditions that inhibit Ch transport such as HC 3, McN-A-343 and "no sodium" increased both the residing and the released [3H]ACh depolarization with high K+ or 4-aminopyridine reduced the residing (79 and 87% of control, respectively) and increased only the released [3H]ACh (182 and 148% of control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284803 TI - Substance P like-immunoreactivity release from enterochromaffin cells of rat caecum mucosa. Inhibition by serotonin and calcium-free medium. AB - Location, endogenous contents, and release of Substance P like-immunoreactivity were investigated in the rat caecum, using Immunohistochemistry and RadioImmunoAssay. Our immunohistochemical results indicate that Substance P was present both in the neuromuscular and mucosal compartments of this intestinal structure. However, detection of the peptide in the enterochromaffin cells of the mucosa remained very difficult. That may be explained by the very low endogenous contents of Substance P detected in the mucosa, using RIA. As we have already described a serotonin release from rat caecum mucosa, we show, now, that Substance P like-immunoreactivity may be released from the same structure. This release was stable, calcium-dependent, inhibited by serotonin, and not influenced by the chemical depolarization. Our data demonstrate an active release of Substance P like-immunoreactivity from intestinal mucosa, in the rat caecum. It seems that the endogenous pool of Substance P like-immunoreactivity is involved as a functional pool. The mechanisms responsible of this release seem to be different than that observed for the serotonin release. Substance P like immunoreactivity may be released in precise physiological conditions, or even, in pathological conditions. PMID- 1284804 TI - Comparison of solution structures of mutant bovine pancreatic trypsin inhibitor proteins using two-dimensional nuclear magnetic resonance. AB - Structural perturbations due to a series of mutations at the 30-51 disulfide bond of bovine pancreatic trypsin inhibitor have been explored using NMR. The mutants replaced cysteines at positions 30 and 51 by alanine at position 51 and alanine, threonine, or valine at position 30. Chemical shift changes occur in residues proximate to the site of mutation. NOE assignments were made using an automated procedure, NASIGN, which used information from the wild-type crystal structure. Intensity information was utilized by a distance geometry algorithm, VEMBED, to generate a series of structures for each protein. Statistical analyses of these structures indicated larger averaged structural perturbations than would be expected from crystallographic and other information. Constrained molecular dynamics refinement using AMBER at 900 K was useful in eliminating structural movements that were not a necessary consequence of the NMR data. In most cases, statistically significant movements are shown to be those greater than approximately 1 A. Such movements do not appear to occur between wild type and A30A51, a result confirmed by crystallography (Eigenbrot, C., Randal, M., & Kossiakoff, A.A., 1990, Protein Eng. 3, 591-598). Structural alterations in the T30A51 or V30A51 mutant proteins near the limits of detection occur in the beta loop (residues 25-28) or C-terminal alpha-helix, respectively. PMID- 1284806 TI - Antigen F1 from Yersinia pestis forms aqueous channels in lipid bilayer membranes. AB - Antigen F1 is a protein of 17 kDa produced by Yersinia pestis when it is cultured at 37 degrees C. When incorporated into planar lipid bilayer membranes this protein induces fluctuations on membrane conductance typical of the formation of ionic channels. These fluctuations reveal two distinct unitary conductance sizes, one in the range of 800 to 1400 pS and the other in the range of 140 to 600 pS. Zero current potential measurements in the presence of a salt gradient show that the channel is not significantly ion selective. The reversal potential measured in the presence of 0.5 M KCl on the cis side and 0.1 M KCl on the trans side was 3.58 +/- 3.98 mV (N = 7). The non-selectivity of the channel, in addition to its large conductance, suggests that it forms large aqueous pores. The present results, taken together with other data showing that antigen F1 inhibits the activity of phagocytic cells, suggest that antigen F1 acts by forming aqueous pores in the membrane of these target cells. PMID- 1284805 TI - Constraints imposed by protease accessibility on the trans-membrane and surface topography of the colicin E1 ion channel. AB - The surface topography of a 190-residue COOH-terminal colicin E1 channel peptide (NH2-Met 333-Ile 522-COOH) bound to uniformly sized 0.2-micron liposomes was probed by accessibility of the peptide to proteases in order (1) to determine whether the channel structure contains trans-membrane segments in addition to the four alpha-helices previously identified and (2) to discriminate between different topographical possibilities for the surface-bound state. An unfolded surface-bound state is indicated by increased trypsin susceptibility of the bound peptide relative to that of the peptide in aqueous solution. The peptide is bound tightly to the membrane surface with Kd < 10(-7) M. The NH2-terminal 50 residues of the membrane-bound peptide are unbound or loosely bound as indicated by their accessibility to proteases, in contrast with the COOH-terminal 140 residues, which are almost protease inaccessible. The general protease accessibility of the NH2-terminal segment Ala 336-Lys 382 excludes any model for the closed channel state that would include trans-membrane helices on the NH2-terminal side of Lys 382. Lys 381-Lys 382 is a major site for protease cleavage of the surface-bound channel peptide. A site for proteinase K cleavage just upstream of the amphiphilic gating hairpin (K420-K461) implies the presence of a surface-exposed segment in this region. These protease accessibility data indicate that it is unlikely that there are any alpha-helices on the NH2-terminal side of the gating hairpin K420-K461 that are inserted into the membrane in the absence of a membrane potential. A model for the topography of an unfolded monomeric surface bound intermediate of the colicin channel domain, including a trans-membrane hydrophobic helical hairpin and two or three long surface-bound helices, is proposed. PMID- 1284807 TI - Some pharmacological properties of prolonged administration of Ukrain in rodents. AB - Some pharmacological properties of Ukrain administered intraperitoneally (i.p.) once daily for three months in mice and rats of both sexes were studied. A three month treatment with Ukrain significantly depressed the spontaneous locomotor activity and did not affect the motor coordination of mice and rats of both sexes. Ukrain did not affect the body weight gain as well as the mass of internal organs; the exception was an increase in the mass of the spleen in rats. Biochemical studies indicated that a three month treatment with Ukrain depressed the whole brain dopamine (DA) concentrations and did not affect the noradrenaline (NA) concentrations. Long-term administration of Ukrain showed no characteristic changes in the concentrations of 5-hydroxytryptamine (5-HT) and 5 hydroxyindoleacetic acid (5-HIAA) in the whole brain. The observed changes after three months' treatment with Ukrain are similar in mice and rats of both sexes. PMID- 1284809 TI - [Medical topics: alleviation of pain and anxiety of cancer patients at their terminal stage]. PMID- 1284808 TI - A cDNA clone representative of a novel splicing pattern of the D. melanogaster dunce gene. AB - The D. melanogaster dunce gene is involved in both the learning and memory processes of the fly. The gene encodes for a cAMP-specific phosphodiesterase, a function playing a central role in the regulation of the intracellular cAMP level. Molecular cloning of dunce has so far not been completely achieved, although it is known that the gene encodes a large set of RNAs and has a complex organization, extending for more than 140 kilobases and containing several genes within its introns. Here we report the isolation and the characterization of 21/7, a cDNA clone representative of a novel dunce splicing pattern. The nucleotide sequence of this clone led to the identification of a dunce exon included in at least one transcript so far uncharacterized. PMID- 1284810 TI - [Molecular biological analysis of cystic fibrosis--a model example for the strategy of "reverse genetics"]. AB - The elucidation of the basic defect causing cystic fibrosis (CF) is a paradigm for the application of "reverse genetics" to the analysis of human genetic disease. Following this strategy, linkage analysis localized the responsible gene for CF on chromosome 7. Chromosome mediated gene transfer and chromosome walking and jumping led to the isolation of the CFTR-gene and its cDNA. A major 3 bp deletion mutation (DeltaF508) and more than 100 other mutations of this gene have been identified as molecular basis of cystic fibrosis. The CFTR-amino acid sequence, obtained by conversion of the cDNA-sequence, indicates that CFTR belongs to a group of integral membrane transport proteins (ABC-proteins). The normal cAMP-stimulated chloride-transport, lacking in CF-cells is restored by transfer and expression of CFTR-cDNA-recombinants in these cells. CFTR is most likely itself a chloride channel. The molecular identification of this gene has already led to substantial advances in diagnosis and prevention of this disease. New therapeutic approaches by pharmacological means or gene therapy are expected from the further molecular and functional analysis of the CFTR-gene. PMID- 1284811 TI - [Hepatitis C virus and renal transplant]. PMID- 1284812 TI - [The treatment of advanced gastric cancer: total gastrectomy "extended" as needed]. AB - Extended resections do play a definite role in the surgical approach to advanced gastric malignancy. Local extension of distant spread of the tumor is no longer to be considered as a contraindication to aggressive surgery based on the evidence that even for palliation, extensive operations, when feasible, have proved to be beneficial in preventing complications related to the natural history of the disease. Over a nine-year period 105 patients with gastric cancer were surgically treated. Out of the 88 patients undergoing tumor excision, 53 were submitted to total gastrectomy (there were 35 males and 18 females, mean age 63 years). This procedure was considered potentially curative in 37 cases and palliative in 16. In 8 of the patients treated with palliation. An extensive procedure, including splenectomy in 7 cases (1 of which with concomitant distal pancreatic resection) and a colonic resection in 1 case, was undertaken. Alimentary continuity following total gastrectomy was restored by jejunal interposition (Mouchet-type reconstruction) in 3 cases, Roux-en-Y esophagojejunostomy in 7 and simple: end-to-side esophagojejunostomy (Sweet and Allen-type) in 6. No postoperative complications have occurred and mean survival time was 8 months with a maximum of 20 months in a patient with a good nutritional status and quality of life (Karnofsky index 78%) who developed no complications related to tumor recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284813 TI - Development of an African-American role model intervention to increase breast self-examination and mammography. AB - Minorities and indigent populations have low participation rates in breast cancer education and screening programs, and suffer from higher morbidity and mortality. Attitudes, norms, and values of such populations are best addressed by breast cancer patients of the same race and cultural background who serve as role models. This article describes the development and pilot study of an intervention program using role models as part of a "Witness" presentation. Programs were held in participants' local African-American churches and community centers. The organization of the program was based on an educational model (4MAT) that identified learning styles and brain hemisphere dominance. Preliminary results with 78 African-American women indicate that the program design is effective in reaching low-income, less-educated African-American women who did not believe themselves to be at high risk for breast cancer. Three-month follow-up demonstrated a significant increase in the practice of BSE and 19% had a mammogram. PMID- 1284815 TI - [The effect of convaflavin on lipid peroxidation in the heart in experimental thyrotoxicosis]. AB - The effect of convaflavin in doses of 30 and 45 mg/kg on lipid peroxidation in the heart was studied in white rats with experimental thyrotoxicosis. A noticeable decrease of the concentration of diene conjugates and malonic dialdehyde was revealed as was activation of catalase and peroxidase under the influence of convaflavin administered in a dose of 45 mg/kg. PMID- 1284814 TI - Carbohydrate binding properties of the envelope glycoproteins of human immunodeficiency virus type 1. AB - Here, we confirm and extend our previous findings on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein N-acetylglucosaminyl binding properties. We show the occurrence of saturable, temperature, pH, and calcium dependent carbohydrate-specific interactions between recombinant precursor gp160 (rgp160) and two affinity matrices: D-mannose-divinylsulfone-agarose, and natural glycoprotein, fetuin, also coupled to agarose. Binding of rgp160 to the matrices was inhibited by soluble mannosyl derivatives, alpha-D-Man17-BSA and mannan, by beta-D-GlcNAc47-BSA and by glycopeptides from Pronase-treated porcine thyroglobulin, which produces oligomannose and complex N-linked glycans. Glycopeptides from Endoglycosidase H-treated thyroglobulin partially inhibited rgp160 binding, as did the asialo-agalacto-tetraantennary precursor oligosaccharide of human alpha 1-acid glycoprotein for binding to fetuin-agarose. beta-D-Glucan and beta-D-Gal17-BSA had no or only limited effect. Also, surface unit rgp120 specifically interacted with fetuin-agarose and soluble fetuin, but in the latter case with a twofold reduced affinity relative to rgp160. After affinity chromatography, rgp160 was specifically retained by the two matrices and eluted by mannan in both cases, while rgp120 was not retained by fetuin-agarose but only eluted as a significantly retarded peak, which confirms its specific but weak interaction. Thus, rgp160 interacts with both oligomannose type, and the mannosyl core of complex type N-linked glycans, and its gp120 region plays a role in this interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284817 TI - The effect of therapy with selected immunomodulators on interleukin-2 production by peripheral blood lymphocytes. PMID- 1284818 TI - Attempts to demonstrate changed reactivity to histamine in laboratory animals after repeated and increasing doses of staphylococcal vaccine. PMID- 1284816 TI - [The effect of sodium salicylate and phenobarbital on the anti-arrhythmia properties of novocainamide and acetylnovocainamide]. AB - CaCl2 and aconitic models of arrhythmias were reproduced in experiments with rats. Sodium salicylate was found to decrease the preventive effect of ecetylnovocainamidum and increased the effect of novocainamidum on ECG changes. Sodium salicylate diminished the preventive effect of acetyl-novocainamidum by elevating myocardial Na+ concentrations, favoured the decrease in myocardial K+ levels, eliminated the preventive effects of novocainamide and acetylnovocainamide by altering myocardial energy metabolism in CaCl2-induced arrhythmia and improved the preventive effect of acetyl-novocainamide on these parameters in aconitic arrhythmia. PMID- 1284819 TI - Specific and non-specific aspects of desensitization using the method of Besredka: experimental sensitization and desensitization of guinea pigs with ovalbumin and bovine serum. PMID- 1284820 TI - Histamine release after nasal challenge with anti-IgE and Staphylococcus aureus in patients with allergic rhinitis. PMID- 1284821 TI - The influence of bacterial antigens on HRF release in patients with chronic obstructive bronchitis. PMID- 1284822 TI - Mediator release and its reinforcement: new aspects of microorganisms in asthma. PMID- 1284823 TI - Modulation of IgE-mediated basophil histamine release by various cytokines. PMID- 1284824 TI - Microbial antigens and cytokines cause type I allergic reactions in AIDS patients. In vitro studies of basophil histamine release. PMID- 1284825 TI - [Surgical procedure in an extensive un-operable decaying breast cancer]. AB - The article indicates necessity of palliative surgical treatment of ulcerating and decaying breast cancers. Ulceration and decay of tumour of the breast make worse the quality of life of the afflicted. The operation like simple mastectomy liquidates the threat of haemorrhage and prevent intoxication from decaying tumour. In the period from 1977 to 1991 year the group of 1075 women with breast cancer were operated. In this number there were 44 women with decaying breast cancer. Sometimes there are difficulties in closing of the operative wound, when women with very extensive tumour ulceration are treated and then reconstructive methods are needed (transposition of a simple skin flap from the opposite breast, a latissimus dorsi myocutaneous flap or omental transposition from the abdomen to the chest wall). All these operated women survived the operation and left surgical ward. PMID- 1284826 TI - Intraventricular administration of substance P induces unattached Purkinje cell dendritic spines in rats. AB - Substance P was infused in the lateral ventricles of twenty Lewis rats for twenty days. The animals under the influence of the substance P demonstrated grooming of the head, the body and the forepaws. On the twentieth day the animals were sacrificed and the cerebellar cortex was processed for electron microscopy. The ultrastructural analysis revealed that although the granule cells, the parallel fibers and the systems of the afferent fibers were intact, numerous unattached Purkinje cell dendritic spines were seen embedded in the soma of the astrocytes, demonstrating postsynaptic differentiation. Numerous unattached spines of the secondary and tertiary dendritic branches of the Purkinje cells were also seen in the molecular layer surrounded by astrocytic sheath. Free unattached spines were also seen not surrounded by any astrocytic process, which did not demonstrate any postsynaptic specialization. The development of unattached Purkinje cell dendritic spines, in an otherwise intact cerebellar cortex, following the intraventricular administration of substance P, suggests that it may act as local growth factor, enforcing the preprogrammed-capability of the Purkinje cells in developing new synaptic surfaces. PMID- 1284827 TI - Developmental screening--a review. PMID- 1284828 TI - [Tissue plasminogen activator, its inhibitor and other parameters of fibrinolysis in blood of patients operated for mild hypertrophy of the prostate]. AB - An increased blood fibrinolytic activity manifested by increased tissue plasminogen activator (t-PA) and decreased tissue plasminogen activator inhibitor (PAI-1) and increased FDP levels are seen in 40 patients with mild hypertrophy of prostate. Surgical treatment increased blood fibrinolytic activity manifested in the increase in t-PA, decrease in PAI-1, shortening of ELT, increase in FDP, and decrease in plasminogen and 2-AP activities. Blood fibrinolytic activity was the highest immediately after surgery with tendency to the gradual normalization. Positive ethanol test and decrease in thrombocyte count indicate and activation of blood clotting system induced by the tissue thrombo-elastins released during surgery. Subclinical DCI with the secondary increased fibrinolysis activation is present in patients with mild hypertrophy of the prostate both prior to and after surgery. PMID- 1284829 TI - [Value of alpha subunit assay in pituitary pathology]. AB - We evaluated serum alpha-subunit concentrations in 72 patients bearing pituitary adenomas. We conclude that: 1) alpha-subunit hypersecretion is found in all patients with TSH secreting pituitary adenoma (n = 10). Two patients have a predominant secretion of alpha-subunit as compared to TSH secretion. 2) As concerns gonadotropin secreting pituitary adenomas (n = 3), all patient have elevated serum alpha-subunit levels with increased FSH and LT concentrations in 2 cases and 1 case respectively. 3) In prolactinomas (n = 14), alpha-subunit concentrations are not significantly different from that of normal subjects. 4) In 11 acromegalic patients, alpha-subunit hypersecretion is found in 2 patients only with GH-alpha and GH-PRL-alpha secreting pituitary adenomas. 5) Among 34 patients with nonsecreting adenomas, 8 have elevated alpha-subunit concentrations (24%). Positive immunocytochemical staining is found in 70% most often with gonadotropins (55%). Only a few pituitary tumors with positive alpha-subunit immunocytochemical staining have elevated serum alpha-subunit levels. At least, the measurement of basal circulating alpha-subunit levels is very useful in the follow-up of patients with nonsecreting adenomas. In our study, medical treatments including bromocriptine and somatostatin analogues have been found effective in patients with alpha-subunit hypersecretion. Further investigations are necessary to prove if such treatments could control tumoral growth and could prevent recurrences. PMID- 1284830 TI - Immuno-histological characterization of OVS1 and OVS2 monoclonal antibodies recognizing human ovarian mucinous cystadenocarcinoma. AB - OVS1 and OVS2 monoclonal antibodies (MAbs) were established by fusing murine myeloma cell line NS1/1-Ag4-1 with mouse spleen cells immunized with fresh human ovarian mucinous-cystadenocarcinoma tissue. The selection of the MAbs was assayed by an immuno-histological (streptavidin-biotin) staining of the specific antigen antibody reaction localized on frozen sections of the same tumor. Other paraffin sections and established cell lines were also screened by immuno-histological staining in order to characterize the specificity and sensitivity of these two MAbs. OVS1 MAb showed 96% specificity and 67% sensitivity to mucinous cystadenocarcinoma with no cross reactions to normal tissue, benign tissue, other cancers, or any established cell lines. OVS2 MAb revealed only 8% specificity but 78% sensitivity to mucinous cystadenocarcinoma, however, a cross reaction to some normal and benign tissues or other cancers was shown. The data suggested that OVS1 and OVS2 MAbs could be used in combination to detect ovarian mucinous cystadenocarcinoma. PMID- 1284831 TI - Use of endotoxin antigens in enzyme-linked immunosorbent assay for the diagnosis of P. pseudomallei infections (melioidosis). AB - An enzyme-linked immunosorbent assay (ELISA) with endotoxin preparations of P. pseudomallei as antigen was developed for detection of IgG antibodies specific to melioidosis. Forty-seven sera of bacteriologically confirmed melioidosis patients, 55 non-melioidosis sera and 50 sera of healthy blood donors from non endemic areas were subjected to this assay in comparison with indirect hemagglutination assay (IHA). The data were treated by receiver operating characteristics analysis. The sensitivity, specificity and accuracy in this ELISA were 95.7%, 94.2%, and 94.7%, respectively, with cut-off value of OD = 0.312 at 490 nm. Meanwhile, those in IHA were 81.0%, 91.4%, and 88.1%, respectively, with a cut-off value of > or = 1:160. From these results, the ELISA was judged to be more reliable than IHA as the seroassay for diagnosis of melioidosis. PMID- 1284832 TI - Immunolocalization of smooth muscle-like cells in the quail ovary. AB - We localized alpha-smooth muscle actin (alpha-SMA) in the quail ovary, using the peroxidase-anti-peroxidase technique. Special attention was paid to the influence of fixation on the immunoreactivity of the antigen. The immunostaining of alpha SMA largely depended on the nature of the fixative. The antigen could most successfully be localized in ovaries fixed in Carnoy's fluid. We also localized alpha-SMA and desmin in semi-thin glycol methacrylate sections of the pre ovulatory follicle, using the immunogold-silver staining method. The sections were pretreated with Lugol's iodine or sodium metaperiodate to enhance the immunoreactivity. alpha-SMA was demonstrated in the cells of the chordae, the tunica albuginea, and the theca externa of each follicle. These structures were inter-connected, forming an ovarian suspensory apparatus. The thecal cells of prelampbrush follicles also expressed alpha-SMA. In the wall of the pre-ovulatory follicle, desmin was found in the cells of the chordae and the tunica albuginea, and in a few cells of the theca externa. In the theca interna, desmin, and sometimes alpha-SMA, was observed in cells adjacent to the endothelium of sinusoids, which are probably pericytes. Our results support the hypothesis that in birds the ovarian follicles possess a thecal contractile system, that is presumably involved in the ovulatory process. PMID- 1284833 TI - Does microwave irradiation have other than thermal effects on histological staining of the mammalian CNS? A light microscopical study of microwave stimulated staining under isothermal conditions in man and rat. AB - The question whether or not microwave irradiation exerts other than thermal effects on histological staining is still a matter of controversy. The present study was undertaken to reveal or reject such a so far hypothetical non-thermal irradiation effect. A device was developed, which enables exposure of histological sections or tissue pieces to microwave irradiation under isothermal conditions, i.e. with synchronous removal of the internal heat produced. Three classical neuroanatomical staining methods were tested on human and rat CNS. As control, identical procedures were performed without simultaneous microwave irradiation. The experiments were performed at three different temperature levels ranging from 5 to 50 degrees C. In none of the cases studied was a light microscopically appreciable difference observed between the microwave and non microwave versions of a stain at the same temperature. The hypothesis of a separate non-thermal effect of microwave irradiation on histological staining is therefore rejected. PMID- 1284834 TI - FK506 reverses adriamycin resistance in a multidrug-resistant human leukemia cell line. AB - We have examined the effect of FK506 on the Adriamycin sensitivity of the multidrug resistant human chronic myelocytic leukemia cell line (K562/ADM). In K562/ADM cells, 1.0 microgram/ml FK506 reversed the resistance of Adriamycin, and increased the IC50 value for Adriamycin up to 17 fold. However, IC50 value for the parent cells (K562) increased only 1.5 fold. By cell cycle analysis, the accumulation in late S-G2M phase was confirmed on K562/ADM cells, treated with 1.0 microgram/ml FK506 and low-dose of Adriamycin. Cyclosporin A (CsA) could also restored the Adriamycin sensitivity in the K562/ADM cells, as previously reported. 1.0 microgram/ml FK506 as well as CsA significantly increased radioactive Adriamycin accumulation in K562/ADM cells and blocked [3H]azidopien photoaffinity labeling of P-glycoprotein. These results suggest that 1.0 microgram/ml FK506 could reverse the Adriamycin resistance in a MDR human leukemia cells through the interaction with P-glycoprotein. PMID- 1284835 TI - Francis Burian--founder of the treatment of facial clefts in Czechoslovakia. AB - Prof. F. Burian, the founder of Czechoslovak Plastic Surgery, belonged to the world-wide scale among the most prominent pioneers of this field. His main interest and professional concern was devoted to the problems of facial clefts. The present communication reviews the gradual development of surgical repair of cleft lip and palate from the early twenties to the late fifties at the Department for Plastic Surgery in Prague, headed by Prof. F. Burian. PMID- 1284836 TI - Configuration of facial profile in adults with cleft lip with or without cleft palate. AB - X-ray cephalometric studies were carried out in 114 adult males with cleft lip and with or without cleft palate. According to the type and extent of the cleft they were subdivided into 4 groups and were compared with a control group of 50 normal males matched in age. Investigated were the parameters of the skeletal and soft facial profile. The results showed that cleft lip alone is associated with deviations of local character concerning only soft tissues within the oronasal region. The ascertained deviations included a flattening of the nose, reduction of the height, concavity and prominence of the upper lip, increased height of the upper lip vermilion and a more horizontal slope of the columella leading to a reduction of the nasolabial angle. Cleft lip and palate was associated with deviations of global character related predominantly to the extent of retrusion of the upper and lower jaw. The skeletal profile was altered and its deviations were reflected by changes of the soft profile. Of the deviations of soft tissues per se were most important the flattening of the nose and reduction of the height and thickness of the upper lip, which underlined the presence of retrocheilia. Maxillary retrusion was more marked in complete than in incomplete unilateral clefts, while mandibular retrusion and maxillary dentoalveolar retroinclination were more marked in bilateral than in unilateral clefts. Occlusion was always impaired. In unilateral involvement, especially in complete clefts the more horizontal slope of the columella resulted in a marked reduction of the nasolabial angle. Incomplete clefts, similarly as cleft lip alone were not associated with a reduction of thickness of the upper lip and showed an increase of the vermilion height. Because of the persisting protrusion of the premaxilla bilateral clefts were accompanied by only a slight flattening of the skeletal profile and by an excessive nasal depth after the prolongation of the columella. The nasolabial angle was unchanged. The concavity of the upper lip was reduced in complete unilateral and bilateral clefts. Certain characteristics of the oronasal region disclosed a similarity between incomplete cleft lip and palate (in unilateral involvement) and cleft lip alone, however global deviations (due to skeletal changes) were identical with those recorded in complete clefts. PMID- 1284837 TI - Configuration of facial profile in adults with isolated cleft palate. AB - X-ray cephalometry was used for the assessment of the configuration of the skeletal and soft tissue profile in 81 adult males with isolated cleft palate. They were assessed in three subgroups, i. e. with complete and incomplete clefts and with clefts of the soft palate alone and were compared with a matched group of controls consisting of 50 normal males, as well as with the situation in the earlier examined series with unilateral cleft lip and palate. In isolated cleft palate both the upper and lower jaws were retruded. The maxilla was most markedly retruded in incomplete clefts and most slightly in clefts of the soft palate alone, while the mandible showed the smallest degree of retrusion in complete clefts. The configuration of the skeletal profile was similar as in unilateral cleft lip and palate, yet positive overjet was on the average restored in all types of isolated cleft palate. A more favourable configuration of the profile was present in patients with cleft soft palate alone, in the absence of an impairment of sagittal jaw relations. Changes in the configuration of the soft profile were due mainly to skeletal deviations. The retrusion of skeletal framework of the middle face was to a large degree masked by the larger thickness of the upper lip, in complete clefts also of the lower lip. Therefore the prominence of the upper lip was only slightly impaired and slight flattening of the face occurred only in complete clefts. The more horizontal slope of the columella resulted in a reduction of the nasolabial angle. Some deviations from the described pattern occurred in clefts of the soft palate alone (steeper slope of the upper lip with an unchanged nasolabial angle, normal thickness of the upper lip a. o.). The findings are suggestive of a differing facial physiognomy in isolated cleft palate. PMID- 1284838 TI - Late results of the surgical treatment in unilateral complete cleft lip and palate. Occlusal and craniofacial characteristics. AB - Sixty-one UCLP patients at 17-20 years of age treated surgically in childhood by M. Krauss were invited for check-up examination to evaluate their occlusal and craniofacial characteristics. Dental study casts were used to determine the dental arch widths and lengths according to Moorrees points and to classify the occlusion according the descriptive and numerical methods. Conventional distances and angles were measured on 45 radiographs. The maxillary canine arch width was smaller by 4 mm than those of the control group, while the maxillary molar arch width did not differ significantly from the normal value. In contrary, the mandibular molar arch width was considerably greater in the studied group than in the control one. The frequency of anterior crossbite was 7%, the lateral crossbite on the cleft side 30%, bilateral crossbite 26% and the crossbite in all segments 16%. In 21% of cases, no crossbite was observed. These results were confirmed by occlusal scoring. The cephalometric analysis showed a decreased maxillary horizontal length and maxillary protrusion angle when compared with the control group, while the anterior upper facial height and incisor inclination angles did not differ significantly. The midface constituted in men 42.5% and in women 42.6% of the total face height. PMID- 1284839 TI - Skin necrosis, a rare complication of coumarin therapy. AB - Coumarin congeners are frequently being prescribed in vascular surgery. The complication most often seen in haemorrhage. A less known complication is necrosis of skin and soft tissues. This rare complication is potentially lethal. The etiology is unclear, a relation with protein C deficiency seems likely. Early treatment with vitamin K and heparin may prevent the skin necrosis. After necrosis has occurred, surgical intervention is usually necessary. PMID- 1284840 TI - Multiple uses of the free radial forearm flap. AB - Presenting clinical cases, the authors show the variety of possible uses of the free radial forearm flap. They employ this sensory flap at sites of increased load such as the area of the planta pedis and in thumb reconstruction. Other potential uses include oesophageal and penile reconstruction. PMID- 1284841 TI - The technique of osteosynthesis in replantations of the upper limb. AB - The authors present their experience in osteosynthesis in replantations in the area of the wrist in 19 patients. For osteosynthesis they use external fixation device, type Poldi 7, which guarantees the stability not only during the microsurgical procedure but also over the whole period of healing. They point out the importance of the resection of both bones ends, i.e. the resection of the comminuted zone, as well as the importance of an extensive fasciotomy. In all patients but one healing was achieved without infection. The authors consider external fixation for the method of choice in the replantation in the wrist area. PMID- 1284842 TI - Use of Becker's prosthesis in breast reconstruction. AB - The method of breast reconstruction using a submuscular permanent expander is rapid and simple, imposing minimal stress on the patient. Using it, it is possible to obtain good shape and size of the reconstructed breast; the ptotic position remains to pose a problem. This modality is useful especially in bilateral involvement and in all patients with a concomitant disease or another risk factor. PMID- 1284843 TI - RecBCD protein as a representative of Escherichia coli DNA helicases. PMID- 1284844 TI - Staphylococcal L-asparaginase: catabolic repression of synthesis. AB - The regulation mechanism of production of staphylococcal L-asparaginase was investigated. The role of cAMP in regulation of its synthesis was confirmed. Production of L-asparaginase from S. aureus NCTC 4135 was inhibited by all carbon sources, mono- and disaccharides added to the growth medium. The strongest inhibition was caused by saccharose and maltose, whereas weaker by galactose, lactose, mannitol and mannose. It was found that exogenous cAMP in the presence of carbon sources stimulated synthesis of the investigated enzyme. PMID- 1284845 TI - Proteinases of Streptomyces fradiae. II. Specificity. AB - It has been shown that extracellular proteinases synthesized by a keratinolytic strain of S. fradiae are characterized by diversified activity in the decomposition of both proteins and synthetic substrates. Among the six proteinases isolated, apart from the ones dominating and having relatively low specificity, there are two enzymes characterized by narrow catalytic abilities- extremely similar to those of trypsin. These proteinases intensively degraded all the trypsin substrates studied, but they were inactive or showed slight activity toward others. They were also highly sensitive to such specific inhibitors of trypsin as TLCK, SBTI and TIO. PMID- 1284847 TI - Isolation and screening of glucose oxidase producing microorganisms from natural sources. AB - Among 1486 mould strains isolated from natural sources (screened for extracellular glucose oxidase) only 119 (Aspergillus and Penicillium) showed this enzyme activity. As the best glucose oxidase producer, A. niger 0-1 was isolated from decaying tree. The dynamics of glucose oxidase synthesis in A. niger 0-1 during its culture by submerged method show that the intracellular activity of this enzyme is 10-times higher than its extracellular level. Some properties of the crude glucose oxidase preparation, isolated from the postculture liquids by lyophilization, were examined. PMID- 1284846 TI - Proteinases of Streptomyces fradiae. III. Catalytic and some physico- chemical properties of keratinolytic proteinase. AB - It has been shown that keratinase--proteinase PIV, the main enzyme of the proteolytic system of S. fradiae, is characterized by high effectiveness in its action on AcAla3OMe--exceeding elastase in catalytic effectiveness several times. This proteinase also cleaves ester and amide bonds formed by the residues of aromatic and basic amino acids, but with a lower effectiveness than chymotrypsin or trypsin. It has also been shown that proteinase IV is a typical serine enzyme highly sensitive to DFP, acting in strongly alkaline pH (about 11.2), with molecular weight 24 kDa and does not contain cysteine. PMID- 1284848 TI - Relationship between citric acid production and accumulation of phytate-degrading enzymes in Aspergillus niger mycelia. AB - The ability of eight strains of Aspergillus niger to produce citric acid by the solid surface method were found to correlate with their capabilities to synthesize intracellular enzymes which degrade phytates (phytase and acid phosphatase). Another high correlation was observed between phytase and acid phosphatase activities bound to the cell walls of mycelia. PMID- 1284849 TI - Comparison of dentrification by Paracoccus denitrificans, Pseudomonas stutzeri and Pseudomonas aeruginosa. AB - The course of denitrification of nitrate, nitrite and both compounds together by static cultures of Paracoccus denitrificans, Pseudomonas stutzeri and Pseudomonas aeruginosa was studied. These strains represent three different types of denitrification: 1. reduction of nitrate to gaseous nitrogen without accumulation of nitrite (P. denitrificans); 2. partial accumulation of nitrite in growing cultures during reduction of nitrate to gaseous nitrogen (P. aeruginosa) and 3. two-phase denitrification that includes reduction of nitrates at the very beginning of the process, and then, after depletion of the former, the reduction of nitrates to gaseous nitrogen (P. stutzeri). These observations differ from the results reported in the literature and possible reasons are discussed. PMID- 1284850 TI - [Etiopathogenesis of chronic liver diseases detected and evaluated using immunologic tests]. PMID- 1284852 TI - Myelin palingenesis. 1. Electron microscopical localization of myelin/oligodendrocyte proteins in multilamellar structures by the immunogold method. AB - The issue of the capacity of mature oligodendrocytes to remyelinate naked axons has not been totally resolved. The impression is that for this to happen, oligodendrocytes have to undergo cell division. We are interested in providing an answer to the question: can oligodendrocytes myelinate more than once? To address this question, we are using a model system consisting of pure cultures of postmyelination oligodendrocytes. We have previously shown that these cells have plasticity and are able to regenerate, but for this to occur they need a signal. In vitro, this signal is provided by interaction with a positively charged substratum and a serum factor(s). Over time in culture, without cell division, oligodendrocytes assemble multilamellar structures that ultrastructurally resemble myelin. We have named this process myelin palingenesis--rebirth--to distinguish it from remyelination. In order to ascertain the significance of the regenerative process observed in vitro and its predictive value as to the capabilities of oligodendrocytes to ensheathe axons, we undertook an ultrastructural and immunocytochemical characterization of the multilamellar membranes to assess whether they contain all the myelin-characteristic proteins, i.e., myelin basic protein, proteolipid protein, 2',3'-cyclic nucleotide 3' phosphodiesterase and myelin-associated glycoprotein. We have used antibodies against these proteins as immunocytochemical probes in conjunction with the immunogold method at the electron microscopic level. Oligodendrocyte cultures were processed for electron microscopy. Blocks were serially sectioned parallel to the culture plate at 0.09-micron spacings. Staining of cells was done prior to embedding. Analysis of these micrographs brought to light the existence of membrane-membrane interaction between multilamellar structures; this is reminiscent of the interactions observed in situ between myelinated axons. We have found that the membranous structures possess all the myelin-characteristic proteins. Furthermore, based on the accessibility of these proteins to the antibodies, e.g., whether or not permeabilization was required, we can surmise that these proteins are incorporated into the membranous structures with the same orientation as in myelin. These results, in conjunction with our earlier work, show that mature oligodendrocytes stripped of their myelin are able to regenerate and reassemble multilamellar membranes that have all the myelin proteins. It remains to be proven that when provided with axons, these oligodendrocytes will generate typical myelin. PMID- 1284851 TI - Cognitive effects of mild head injury in children and adolescents. AB - A comprehensive review of recent neuropsychological studies of mild head injury (MHI) involving children and adolescents is presented. The seminal work of Rutter and his colleagues is reviewed. An alternative conceptualization of MHI as proposed by various researchers is elaborated and further research investigating the cognitive sequelae of MHI is reviewed. MHI is discussed within the context of development and information processing models. Finally, the sequelae of MHI are reviewed with respect to academic functioning. Methodological problems inherent in studies of MHI are identified and discussed. The studies reviewed here support the conclusion that both the cognitive and emotional consequences of MHI should receive serious evaluation. PMID- 1284853 TI - Carbohydrate moieties of myelin-associated glycoprotein, major glycoprotein of the peripheral nervous system myelin and other myelin glycoproteins potentially involved in cell adhesion. AB - The myelin-associated glycoprotein (MAG) and the major glycoprotein of the peripheral nervous system myelin (P0) are two members of the family of cell adhesion molecules (CAMs). A role in cell adhesion of the carbohydrate moiety of these molecules has been attributed to the presence of N-glycans bearing the HNK 1 carbohydrate epitope. On the other hand, it has been suggested that these glycoproteins could be ligands of an endogenous mannose-binding lectin present in myelin, the cerebellar soluble lectin (CSL). In order to further document the heterogeneity of the glycans of these two CAMs, we have used several probes: an anti-carbohydrate antibody of the HNK-1 type, called Elec-39, the plant lectin concanavalin A (ConA), and the endogenous lectin CSL involved in myelin compaction. This study shows that CSL binds to a small proportion of the polypeptide chains of MAG found in adult CNS of rats and man and the polypeptide chains of P0 molecules from adult human and rat sciatic nerve. For MAG from adult rat brain, the binding of CSL is restricted to glycans of polypeptide chains which could be separated from the others according to their solubility properties. These MAG molecular entities react also with the Elec-39 antibody and with ConA. These results confirm that P0 and MAG are heterogeneous in their carbohydrate moieties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284854 TI - [Alveolar macrophages and granuloma formation]. AB - We measured intracytoplasmic free calcium ion concentration ([Ca3+]i) of alveolar macrophages (AMs) in order to elucidate the mechanism(s) of lipopolysaccharide (LPS)-hyperresponsiveness of AMs in patients with sarcoidosis at the second messenger level. Resting [Ca2+]i was higher in patients with sarcoidosis than in normal subjects. [Ca2+]i increase responses were also elevated in patients with sarcoidosis when AMs were stimulated with either anti-CD14 (a LPS/LPS-binding protein complex receptor) antibody, anti-CD64 (Fc gamma receptor I), antibody or platelet activating factor. After incubation with interferon-gamma, resting [Ca2+]i and increase in [Ca2+]i induced by anti-CD14 antibody stimulation were higher in patients with sarcoidosis as compared with values before incubation. Thus, these data suggest that activation of AMs at the second messenger level induced by IFN gamma, at least in part, accounts for LPS-hyperresponsiveness in sarcoidosis. PMID- 1284855 TI - [Lipopolysaccharide binding protein enhances intratracheally administrated lipopolysaccharide-induced acute lung inflammation via a CD14 receptor]. AB - We examined the role of lipopolysaccharide binding protein (LBP) in the airspace and the CD14 receptor on alveolar macrophages in TNF alpha production and neutrophil (PMN) sequestration in lungs induced by intratracheal injection of lipopolysaccharide (LPS). LPS alone (Salmonella minnesota wild-type; 20 ng) or LPS + LBP complex [LPS (20 ng) + rabbit LBP (500 ng); preincubated for 30 min at 37 degrees C] was injected intratracheally into isolated rabbit lungs perfused with lactate-Ringer-albumin solution. Human PMN (5 x 10(7)) were added to the perfusate after 2 hr perfusion. Samples of lung perfusate were collected every 30 min for 180 min, after which bronchoalveolar lavage (BAL) was also performed. TNF alpha concentration in the perfusate and BAL fluid were determined using a bioassay with L-929 fibroblasts. PMN accumulation in the lung was determined by myeloperoxidase assay of the lung homogenate. LPS alone did not significantly increase TNF alpha production or PMN accumulation in lungs, whereas LPS/LBP complex increased TNF alpha concentration in the perfusate and PMN accumulation. Intratracheal injection of anti-CD14 antibody (40 micrograms) with LPS/LBP complex prevented TNF alpha production and subsequent PMN sequestration. We conclude that LBP in the airspace enhances the effect of LPS on TNF alpha production via a CD14-dependent pathway, and this subsequently contributes to PMN sequestration in the lungs. Airspace accumulation of LBP secondary to increased vascular and epithelial permeability may play a critical role in the development of septic shock and lung injury by promoting TNF alpha production via a CD14 dependent mechanism. PMID- 1284856 TI - [The extravasation of vesicant drugs: a report of experience]. PMID- 1284857 TI - Heparin-binding (fibroblast) growth factors are potential autocrine regulators of esophageal epithelial cell proliferation. AB - A serum-free culture system supplemented with neural tissue extract for normal human esophagus was applied to the culture of mouse esophageal epithelium. Similar to mouse mesenchyme and skin epithelium, esophageal epithelial lines (MEE) emerged after serial culture. The cells had an apparent unlimited life span, but retained morphology and other characteristics of normal epithelial cells. A screen for growth factors that stimulated growth of MEE cells in the absence of neural extract revealed that epidermal growth factor (EGF) and heparin binding (fibroblast) growth factors (HBGF) were most effective. An HBGF-like activity was apparent in extracts of rapidly proliferating, but not quiescent MEE cells at low or confluent densities. A cloned cell line (MEE/C8) was selected from MEE cell cultures in the absence of neural extract. MEE/C8 cells proliferated independent of either EGF or HBGF at rates equal to MEE cells, cell extracts exhibited HBGF-like activity at all stages of proliferation, and the cells formed invasive tumors in syngenic hosts. The HBGF-like activity present in extracts of tumorigenic MEE/C8 cells had properties similar to HBGF-1 (acidic fibroblast growth factor). PMID- 1284858 TI - Allogeneic bone marrow transplantation for malignant hematologic disorders in children. AB - In the present study we carried out allogeneic bone marrow transplantation (BMT) in 14 leukemia children with high risk prognostic factors. Six patients with acute nonlymphocytic leukemia (ANLL), four with acute lymphocytic leukemia (ALL), two with chronic myelogenous leukemia (CML), and two with myelodysplastic syndrome (MDS). Among these patients, six with ANLL, two with ALL, one with CML and one with MDS were alive in complete remission 8 to 58 months post-BMT. Four patients died of relapse (one with ALL, and one with MDS), and chronic GVHD (one with ALL and one with CML). In six patients recombinant granulocyte colony stimulating factor (rG-CSF) was used to shorten the period of granulocytopenia. The mean time of recovery to granulocyte count of 500/mm3 was 13.2 days in the rG CSF+ group, being 15.9 days faster than that in the rG-CSF- group. In light of these results, allogeneic BMT is shown to be a choice of treatment for leukemia children with high risk prognostic factors and rG-CSF may be an effective reagent to prevent infectious episodes in BMT. PMID- 1284859 TI - Mechanisms for appearance of no-flow areas in tumor microvascular bed. AB - In order to elucidate the mechanism for appearance of no-flow areas (areas where tumor blood flow temporarily cease), we directly observed the process of tumor induced neovascularization and measured pressure change in a feeding vessel (starting vessel) which supplies blood to the tumor vascular network. Total length of tumor vascular network from one starting vessel increased exponentially as the tumor increased in size exponentially. The pressure of the starting vessel increased from approximately 40 cmH2O to 120 cmH2O with enlargement of the tumor size. As soon as the pressure of the starting vessel reached a plateau, however, there was a rapid increase in low-flow or no-flow areas in places within the tumor. We considered that no-flow areas were produced by the imbalance between the pressure elevation of a starting vessel and the enlargement of the vascular network from that vessel. PMID- 1284860 TI - Beyond three: MCH nurses' assessment leads to early interventions. AB - This study reports the results of a one year trial of a comprehensive developmental assessment, including vision and hearing screening, of three to four year olds in one municipality. Initial results indicated that over 50% of the 790 children assessed had no identifiable problems, this increased a further 15% after retesting. One hundred and eighty-seven children were referred to a variety of agencies, mainly for vision and audiological reassessment. One hundred and thirty-five referrals for further investigation were for children whose problems were confirmed and appropriately managed. PMID- 1284861 TI - Enhanced learning produced by injection of neurokinin substance P into the region of the nucleus basalis magnocellularis: mediation by the N-terminal sequence. AB - The effect of unilateral injection of the neurokinin substance P (SP) and of certain N- or C-terminal SP-fragments into the region of the nucleus basalis magnocellularis (NBM) on inhibitory avoidance learning was investigated. Rats with chronically implanted cannulae were tested on a one-trial uphill avoidance task. Immediately after the training trial, rats were injected with 0.74 pmol SP or equimolar dosed SP(1-7), DIME-C7, or SP(7-11). Control groups included vehicle injected rats and a group given an injection of SP(1-7) 5-h after the trial. When tested 24 h later, rats treated with SP or SP(1-7), but not with DIME-C7 or SP(7 11), exhibited longer step-up latencies than vehicle-treated controls. The retention latencies for rats in the SP(1-7) 5-h delay group did not differ from those of vehicle-injected animals, ruling out proactive effects of SP(1-7) on performance. The results show that SP facilitates retention of an inhibitory avoidance response when injected into the NBM. Furthermore, the amino acid sequence that encodes this effect may be located in the N-terminal part of the SP molecule. PMID- 1284862 TI - Plasticity of the sympathetic nervous system innervating the cerebral arteries in rats. AB - In order to investigate the neuroplasticity of the peripheral sympathetic nervous system innervating the cerebral blood vessels, we observed and traced the sprouting nerve fibers originating in the contralateral superior cervical ganglion (SCG) into the previously denervated cerebral arteries following unilateral excision of the SCG and/or decentralization of the contralateral SCG in young rats (4 weeks old). These nerve fibers were labeled anterogradely with wheat germ agglutinin-horseradish peroxidase or stained immunohistochemically with anti-tyrosine hydroxylase antibody. Eight weeks after the right SCG excision, reinnervating nerve fibers originating in the contralateral ganglion formed a circular pattern of nerve plexus only on the wall of the main cerebral arteries of the circle of Willis in the ganglionectomized side. However, the decentralization of the contralateral SCG, which was performed simultaneously with a unilateral SCG excision, prevented the nerve sprouting into the denervated regions. Unilateral decentralization of SCG itself failed to affect their distribution pattern or their density of nerve fibers originating in the ganglion. It is concluded that in the young rat the outgrowth of the sympathetic nerve fibers into the denervated cerebral arteries was strongly impeded by the disconnection of ganglion cells from the central nervous system, while the decentralization alone could not affect the innervation pattern of the postganglionic fibers which have been already built-up in the cerebral arterial system. PMID- 1284863 TI - Signals that induce sprouting in the central nervous system: sprouting is delayed in a strain of mouse exhibiting delayed axonal degeneration. AB - This study evaluates whether CNS sprouting is initiated by signals related to the degeneration of presynaptic axons. We evaluate the time course of sprouting of cholinergic septohippocampal fibers after unilateral entorhinal cortex (EC) lesions in a substrain of mice carrying a mutation which leads to a substantial delay in the onset of Wallerian degeneration. We first verified that axonal degeneration resulting from EC lesions was delayed in mutant mice using silver staining techniques (the Fink-Heimer method). Cholinergic sprouting was then evaluated using a histochemical technique for acetylcholinesterase (AChE) in mutant mice and normal controls. In normal control mice, both axonal degeneration and cholinergic sprouting occurred with a time course that was comparable to that described in rats. Argyrophilic degeneration debris was prominent by 4 days postlesion, and increases in AChE staining in the molecular layer of the dentate gyrus were well developed by 10 days. In mice carrying the "Ola" mutation, however, argyrophilic degeneration debris was not detectable at 4 or 6 days postlesion, began to appear in the dentate gyrus by 8 days postlesion, but did not become prominent until 12 days. Increases in AChE staining in the molecular layer of the dentate gyrus were not detectable even at 12 days postlesion, but developed gradually after 14 days. These results demonstrate that the signals which initiate at least one form of CNS sprouting are related to the degeneration of presynaptic axons. PMID- 1284864 TI - Monoclonal antibodies against potato virus A--competitive binding tests. AB - Six mouse monoclonal antibodies (MoAbs) against potato virus A (PVA) were tested. One of them (PVA 534) reacted only with complete virions and was apparently specific for epitopes dependent on quaternary structure. MoAb PVA 328 recognized the virus antigen only after its dissociation into subunits. MoAb PVA 328 must have reacted with a cryptotope of the antigen. MoAb PVA 151 and 290 appeared to be conformation independent and reacted with exposed regions on native virus particles as well as on the surface of dissociated coat protein subunits. Two other MoAbs (PVA 187 and 634) did not recognize subunits or the virions adsorbed directly to the microtiter plate. This seems to be an evidence of metatope existence. The results of competitive binding tests combined with the reaction patterns of individual MoAbs to different potyviruses indicate that the MoAbs are specific for 6 distinct epitopes. PMID- 1284865 TI - Herpes simplex virus type 2 and pseudorabies virus associated growth factors and their role in the latency in vitro. AB - A putative herpes simplex virus type 2 (HSV-2) growth factor (HSGF-2) was detected in a crude extract from virus infected mouse embryo cells. This factor, similar to previously described pseudorabies virus (PRV) associated growth factor (PRGF) was shown to have ability to morphologically transform non-transformed cells and to repress the transformed phenotype of transformed cells. Both activities could be neutralized with two, out of seven monoclonal antibodies directed against glycoprotein B of HSV-2. Both PRGF and HSGF-2 were detected in human embryo lung cells latently infected with PRV or HSV-2 either at 41 degrees C, or in the presence of phosphonoacetic acid. Human alpha-2 interferon, when present in medium of latently infected cells enhanced the production of both HSGF and PRGF. On the contrary, when latently infected cells were treated with 5 azacytidine the synthesis of both PRGF and HSGF-2 was completely blocked and the virus reactivated from latency replicated to higher titers than in non-treated cells. The role of PRGF and HSGF-2 in the establishment, maintenance and reactivation of latency, as well as in cellular transformation is discussed. PMID- 1284866 TI - Determination of antibodies to non-structural and structural adenovirus antigens by ELISA. AB - We evaluated possibilities to analyze serum antibodies to non-structural (peptides derived from adenovirus E1b protein) and structural (hexon) adenovirus antigens by ELISA. Synthetic dodecapeptides covering a putative A-gliadin cross reactive antigenic determinant of the E1b protein were used. The aminoterminus of the peptides appeared to be important for antibody binding but the exact sequence of a possible common B-cell epitope within the peptides remained open. Coupling of the peptides to a carrier protein was essential for ELISA analyses of serum antipeptide antibodies. IgA antibodies to both adenovirus derived E1b peptides and hexon antigen could be detected already two weeks after the onset of an acute adenovirus infection, while antipeptide IgG antibodies were seen in a restricted number of patients only. PMID- 1284867 TI - Preparation and characterization of the monoclonal antibodies against Japanese encephalitis virus. AB - Six mouse monoclonal antibodies (MoAbs) against Japanese encephalitis virus (JEV) were prepared and analyzed with indirect immunofluorescence assay (IFA), enzyme linked immunosorbent assay (ELISA), haemagglutination inhibition test (HI), neutralization test (NT), antibody dependent cell mediated cytotoxicity (ADCC) assay, antigenic site specific analysis and relative affinity measurement. These MoAbs could be divided into three classes by indirect immunofluorescence cross reactivity among four flaviviruses, 2H4, 2F2, and nG2 were type specific; 2D2 and mC3 were subgroup specific; and mG9 was family specific. 2H4 and 2F2 had higher neutralization activity, 2D2 and mC3 had the function of inducing ADCC effect, mG9 had higher titer in HI. The six MoAbs recognized five antigenic sites on JEV envelope glycoprotein, 2H4 and 2F2 recognized the same or very similar antigenic site and their relative affinity was ranked as: nG2 > 2H4 > 2D2 > mG9 > 2F2 > mC3. PMID- 1284868 TI - Common and different antigenic properties of the rabies virus glycoprotein of strains SAD-Vnukovo and Pitman-Moore. AB - Two fixed rabies virus strains, SAD-Vnukovo and Pitman-Moore (PM) were used as combined immunogens for the generation of hybridomas secreting specific monoclonal antibodies (MoAbs). The obtained hybridomas were primarily screened by an ELISA for production of MoAbs to antigen of SAD-Vnukovo strain. Six positive clones were established. A panel of MoAbs has been characterized according to reactivity in immunofluorescence, immunoblot, ELISA and neutralization tests. All MoAbs were positive in immunofluorescence when cells infected with the SAD Vnukovo strain were used. By immunoblot, four MoAbs showed specificity for the viral glycoprotein of both SAD-Vnukovo and PM rabies strains. This pattern of reactivity indicated the existence of shared conformation-independent epitopes located on the related antigens. However, in ELISA, the tested MoAbs did not recognize viral glycoproteins of the PM strain. This indicates, that the different strain-specific conformations of the native glycoprotein determine the accessibility of the common linear determinants for respective antibodies. Only one antibody, with conformation-dependent glycoprotein specificity, was capable to neutralize the CVS strain of rabies virus. PMID- 1284869 TI - Synthesis of 23 K acute-phase protein by HBV genome carrying PLC/PRF/5 human hepatoma cells. AB - Elevated synthesis of 23 K protein by human hepatoma PLC/PRF/5 cells was observed after their treatment with conditioned medium from concanavalin A stimulated peripheral-blood monocytes. Increased amount of this protein was first determined 4 hr after the treatment and its maximal level was reached 48 hr later. The role of the 23 K protein remains so far unknown. PMID- 1284870 TI - Platelet-derived growth factor is angiogenic in vivo. AB - PDGF receptors have recently been found to be expressed in microvascular endothelium in vivo under circumstances of endothelial cell activation and angiogenesis suggesting that PDGF may have a direct effect on endothelial cells. We have tested the angiogenic activity of PDGF-AA and -BB homodimers in the chick chorioallantoic membrane in vivo. PDGF-BB was found to consistently induce an angiogenic response whereas PDGF-AA was less active. Morphological analyses revealed that there was little inflammation associated with this response but an increase in vessel density suggested a direct effect of PDGF on embryonic chorioallantoic endothelial cells. In vitro, PDGF-BB was found to be more potent than PDGF-AA in stimulating the chemotaxis of rat brain capillary endothelial cells. This is consistent with a direct effect of PDGF on endothelial cells. Thus, this novel angiogenic activity of PDGF has implications for several developmental and pathological events in which PDGF, particularly the B-chain, is expressed. PMID- 1284871 TI - Insulin-like growth factor-1 stimulates proliferation of myeloid FDC-P1 cells overexpressing the human colony-stimulating factor-1 receptor. AB - Retrovirally expressed human CSF-1 receptor can induce CSF-1-dependent growth of IL-3-dependent hemopoietic cells FDC-P1. Here we show that expression of the human CSF-1 receptor also allowed FDC-P1 cells to grow in response to Insulin like Growth Factor-1 (IGF-I). The authentic receptor for IGF-I was identified by affinity cross-linking and binding analysis on both control (infected with a neo vector) and CSF-1 receptor expressing FDC-P1 cells. DNA and RNA analysis of these cells and of five clones of IGF-I responsive cells demonstrated that the IGF-I receptor gene was not rearranged nor was it abnormally expressed in IGF-I responsive cells. These results suggest that myeloid cells over-expressing CSF-1R (c-fms protooncogene product) might have a proliferative advantage over normal myeloid cells in a physiological situation, independently of the presence of CSF 1 or the capacity of the cells to respond to CSF-1. This would indicate a possible role for c-fms in human neoplasia. PMID- 1284872 TI - HLA matching: a comparison of conventional and molecular approaches. AB - 1. The UNOS national sharing program has produced a 5-fold increase in the number of compatible transplants since 1987. 2. Transplants with 0 broad HLA-antigen mismatches had 87% 1-year graft survival and an 18-year half-life, essentially the same result as with conventional matching. 3. Equally impressive results were obtained with public determinant matching: 1-year graft survival ranging from 84 to 88% and a half-life of 12-15 years. 4. Increasing the number of matched determinants improved the results but reduced the number of compatible recipients identified. 5. Less than 10% of the current transplants have 0 public determinants mismatched. This fraction could be increased to 66% with local sharing and to over 90% with national sharing. 6. The results for cadaver transplants would approach those of related kidneys if compatible grafts were transplanted at the 90% rate obtainable with molecular matching. PMID- 1284873 TI - Results of chemotherapy plus external reirradiation in the treatment of locally advanced recurrences of nasopharyngeal carcinoma. AB - Between 1982 and 1991, 16 patients with recurrent cancer of the nasopharynx were treated with chemotherapy (CT) and radiotherapy (RT). All patients had received prior RT (45-69, 30 Gy). According to rTNM there were three rT2, one rT3 and 12 rT4. 5 patients were N1. Reirradiation (12-46 Gy, mean: 28) started 3-4 weeks after CT (2-6 cycles of different combinations), but 2 cases involved concomitant therapy. Out of 16 patients 7 had complete response (CR) (43.7%), 7 partial response and 2 no response. Statistically significant prognostic factors for obtaining CR were time of relapse and response to initial CT. Median duration of CR was 22+ months (9-64+). Failures at primary site occurred in 3 patients, 2/2 of those receiving CT without platinum compounds and 1/5 of other ones, with statistically significant difference in local recurrence free-survival between the two groups. Two- and 3-year actuarial overall survival were 28% and 10%. Rates of disease-free survival were 17% and 8%, respectively. The acute toxicity was generally mild. No central nervous system damage or radiation-induced myelitis were observed in survivors. PMID- 1284875 TI - [Substance P and the resistance of biological motivations to ethanol]. AB - Ability of the substance P to enhance the tolerance of feeding and defence motivations of ethanol was studied in rabbits. Ethanol led to disintegration of central mechanisms of both feeding and escape responses elicited by a threshold electrical stimulation of lateral and ventromedial hypothalamic centres. Subsequent i.v. administration of the substance P restored the effects of midbrain RF on the motivational centres. The inhibitory effect of the dorsal hippocampus and the facilitatory effect of the midbrain RF on excitability of the lateral hypothalamus, are also restored. The data obtained suggest that the substance P is able to increase a tolerance of the central mechanisms of biological motivations of ethanol. PMID- 1284874 TI - Salivary flow and composition in lymphoma patients before, during and after treatment with cytostatic drugs. AB - To investigate the effect of modern, intensive chemotherapy on salivary flow rate and composition, 79 patients suffering from Hodgkin's disease or non-Hodgkin lymphoma were studied before, during and after administration of cytostatic drugs. 49 patients (mean age 49.9 years, 30 men, 19 women) completed the 1-year study. All patients who received radiotherapy or medication other than cytostatics were excluded. The results showed no marked differences in stimulated salivary flow rates, buffering capacities and amylase and total protein concentrations between the beginning and the end of the 12 month trial. However, significant increases in albumin secretion into saliva and salivary lysozyme concentrations were observed. Total salivary IgG, IgA and IgM concentrations decreased significantly during the cancer therapy but values returned to the baseline levels after termination of treatment. Despite the well-known cytolytic effect of anticancer drugs, chemotherapy need not therefore be permanently detrimental to saliva. PMID- 1284876 TI - [The localization of the neurons in the cat stellate ganglion]. AB - Localisation of HRP-labelled neurons in the stellate ganglion was studied. The neurons in the ganglion seem to be organised according to the topic principle. PMID- 1284877 TI - What constitutes a specialty? PMID- 1284878 TI - [An etiological study on fulminant viral hepatitis]. AB - Viral markers were studied in 79 cases of viral hepatitis with hepatic failure. The results were shown as follows: 8 cases were positive for anti-HAV IgM (10.12%); 76 cases positive for HBsAg or anti-HBc IgM (96.20%) and 41 cases positive for anti-HCV antibodies (51.89%). Among those with anti-HCV positive, 35 cases were co-infected with HBV, 5 cases with HAV and/or HCV, only one was infected with HCV alone 2 cases were HD-Ag positive (2.52%) and one not identified (1.27%). With the reference of clinical findings, patients co-infected with HBV/HCV or anti-HBc IgM positive were more critical and usually entail higher mortality. In cases with HCV co-infections, the positive HBV replication markers seems to be reduced. Hepatic failure without HBV replicative markers had a high rate of hepatic coma as well as poor outcome. PMID- 1284879 TI - Serosurveillance for Pseudomonas pseudomallei infection in Thailand. AB - A nation-wide survey was conducted to see the prevalence of serosensitivity to Pseudomonas pseudomallei antigens by indirect hemagglutination (IHA) and indirect immunofluorescent assay (IFA) for IgG and IgM. Serum samples were collected from blood donors in eight selected areas and bacteriologically confirmed melioidosis patients in Ubon Ratchathani province. The distribution patterns of antibody titers were compared among the survey areas with cut-off points set at 1:160 for IHA, 1:4 for IFA-IgM and 1:32 for IFA-IgG. These cut-off points were decided by ROC (Receiver Operating Characteristics) analysis. The specificity (% true negative reactions) of each serological test in the general population differed significantly among survey areas, possibly reflecting the extent of inapparent infection in each community. IFA was more successful than IHA in differentiating between negative from positive reactions. The survey classified the areas into endemic (Khon Kaen, Ubon Ratchathani), transported (Bangkok), and non-endemic (other provinces) types. PMID- 1284880 TI - Serosurveillance for double infection with Pseudomonas pseudomallei in tuberculous patients. AB - The serosensitivity to Pseudomonas pseudomallei antigen in pulmonary tuberculous patients was surveyed in Ubon Ratchathani Province, a melioidosis-endemic and tuberculosis-prevalent area in Thailand. Indirect hemagglutination assay (IHA) and indirect immunofluorescent assay (IFA) for IgM and IgG were employed for the measurement of antibody levels, with cut-off points set at 1:160, 1:8, and 1:32, respectively. Retrospective protocol survey of clinical data was also conducted. From these studies, however, no evidence was obtained to show that tuberculous patients have a disposition to acquire double-infected with P. pseudomallei and to develop melioidosis. The serosensitivity was never higher than that of the general population of the province as represented by healthy blood donors, nor related with the clinical severeness. Tuberculosis and melioidosis appear to be mutually independent diseases without showing interrelated prevalence in the endemic area. PMID- 1284881 TI - [Enhancing the reparative potentials of the cellular structures in the hypothalamus by the preliminary adaptation of animals to hypoxia and stress]. AB - Effects of preliminary adaptation of rats to hypoxic hypoxia and short-term stress environments on the dynamics of the repair changes of RNA and proteins in the cellular structures of supraoptic (SON) and paraventricular (PVN) nuclei of hypothalamus are studied. Adaptation to hypoxia and short-term stresses is found to increase the potential of protein-synthetizing system of neuro- and gliocytes of SON and PVN. It prevented a marked decrease in the RNA and proteins contents during a post-stress period and increased an intensity of the repair processes in the nuclei being tested. Experimental findings are indicative of a heterochronic pattern of repair processes in hypothalamic neurosecretory structures which to a great extent can be related with their potentials to rearrange the intracellular metabolism for maximum functional maintenance during stresses. PMID- 1284882 TI - False positive stress ECG: ST-depression due to ventricular premature contractions unrecognized by the computer programme. PMID- 1284883 TI - [Drug treatment of chronic ventricular arrhythmia]. AB - The treatment of chronic ventricular arrhythmias depends on the severity and tolerance of the arrhythmia. Extrasystoles, even repetitive, in the healthy heart, are usually respected when asymptomatic or treated with betablockers in first intention when symptomatic. These drugs should also be proposed for patients with ischemic heart disease and non-sustained ventricular tachycardia, a situation in which Class I antiarrhythmics should be avoided. The prevention of sustained ventricular tachycardial may be empirical, with betablockers and/or amiodarone, or guided by the results of pharmacological tests during endocavitary electrophysiological studies. PMID- 1284884 TI - [Post-transfusion non-A, non-B hepatitis: towards risk zero]. PMID- 1284885 TI - [Immunological parameters in the differential diagnosis of ascites secondary to peritoneal carcinomatosis, hepatic cirrhosis, and congestive heart failure]. AB - As a contribution to the study of ascites in patients with liver cirrhosis, congestive heart failure and peritoneal carcinomatosis evaluate in serum and ascites the concentrations of alphafetoprotein, carcinoembryonic antigen and fibronectin, they might suggest a diagnosis for the basic pathology. Forty-seven patients were studied, from whom 23 with cirrhosis, 17 peritoneal carcinomatosis and 7 with congestive heart failure. We conclude that: a) none of the tools usually employed in the analysis of ascitic fluid alone can make the base pathological process responsible for producing ascites; b) fibronectins were more useful for differential diagnosis between cirrhosis and carcinomatosis; c) alpha fetoprotein and carcinoembryonic antigen were not useful for the definition for differential diagnosis. PMID- 1284886 TI - The immunogenetics of immune senescence. AB - Immune senescence is characterized by a dysregulation of the immune system. With respect to humoral immunity, aging is associated with an increased level of many autoantibodies and a decreased antibody response to most foreign antigens. This observation reflects a decreased capacity to activate antibody production by CD5 negative B cells despite a normal or increased capacity to generate antibodies produced by the CD5-positive B cells. A similar dysregulation of cell-mediated immunity is manifested by an altered balance in cytokine production by T cells from old as compared to young subjects. Thus, the production of interleukin-2 (IL 2), IL-3 and granulocyte-macrophage colony-stimulating factor by T cells from old subjects is decreased although the production of IL-4, IL-5 and IL-6 is undiminished or actually increased. PMID- 1284887 TI - Cystic fibrosis mice have arrived! PMID- 1284888 TI - CFTR nonsense mutations G542X and W1282X associated with severe reduction of CFTR mRNA in nasal epithelial cells. PMID- 1284889 TI - A novel frame-shift mutation in exon 4 of the cystic fibrosis gene (435insA) demonstrates the ambiguity of restriction analysis for mutation screening. PMID- 1284891 TI - USAN Council. List No. 340. New names. Lenograstim. PMID- 1284890 TI - An EcoRI RFLP at the human insulin-like growth factor binding protein 2 gene (IGFBP2). PMID- 1284892 TI - [Major complications after open prostatectomy: management and prevention]. AB - From Jan. 1976 to Dec. 1989, 829 patients with benign prostatic hyperplasia (BPH) were treated. Open prostatectomy was performed successfully in 571 patients. Secondary hemorrhage was observed in 21 patients (3.7%), bladder neck or posterior urethral stricture in 10 (1.7%), and temporary incontinence in 21 (3.7%). No operative mortality was noted. The pathogenesis, management and prevention of those complications were detailed with review of the literatures. Effective hemostasis, proper enucleation of the enlarged gland and meticulous reconstruction of the bladder neck are claimed to be the key points in reducing complications and increasing cure rate in the treatment of BPH with open prostatectomy. PMID- 1284893 TI - [The importance of fixation in immunohistochemistry: distribution of vimentin and cytokeratins in samples fixed in alcohol and formol]. AB - The fixation in ethanol or formalin for trypsin digestion in immunohistochemical detection of cytokeratins and vimentin was assessed in a case of ovarian cystadenofibrocarcinoma. Superior reactivity for both markers was achieved in ethanol-fixed sections, even in samples stocked up to 60 days. Cytokeratin reaction in formalin-fixed sections was better when trypsin was used. However, this digestion was deleterious to vimentin detection. These data are presented to alert surgeons and oncologists on the relevance of fixation of specimens suspicious for neoplasia, since different epitopes may require different fixatives and the inadequate choice in the operative room may impart difficulties when immunohistochemistry is necessary. PMID- 1284894 TI - Comparative study of adenoviruses with monoclonal antibodies. AB - The obtainment of monoclonal antibodies for adenovirus species 4(Ad4) is described. The specificities of selected monoclonal antibodies were determined by means of viral neutralization test in cell culture, immunofluorescence and Enzyme Linked Immunosorbent Assay (ELISA), in the presence of the following species of human adenovirus: 1, 2, 5 (subgenus C), 4 (subgenus E), 7 and 16 (subgenus B) and 9 (subgenus D). Two monoclonal antibodies species specific to adenovirus 4 (1CIII and 3DIII) and one monoclonal antibody that cross reacted with adenovirus species 4 and 7 (2HIII) were obtained. PMID- 1284895 TI - [Thermostability of rabies vaccine, type Fuenzalida & Palacios, for human use]. AB - Ten lots of Fuenzalida & Palacios type antirabies vaccine for human use, produced at the Instituto Butantan (Sao Paulo, Brazil) were stored at temperatures of 45, 37, 28 and 2-8 degrees C. The potency of each lot was determined in samples taken at varied time intervals using the NIH method and lots presenting antigenic values > or = 0,3 were considered satisfactory for use. After 2 hours at 45 degrees C the antigenic value of one out of 10 lots tested was found to be less than the minimum required value. At 37 degrees C all lots maintained satisfactory antigenic values until the third day of storage, whilst at 28 and 2-8 degrees C the potency was fully maintained, respectively for 10 and 360 days. At the ideal temperature of 2-8 degrees C, 100% of the tested vaccines maintained the minimum required antigenicity for a longer period (16 months) than the expiration time of 6-12 months usually recommended for this type of biological produced in Latin American and Caribbean countries. Thus, the obtained data suggested that in countries still producing Fuenzalida & Palacios type vaccine, the expiration tim could be extended to 16 months, what could prevent the unnecessary discarding of products still in useful condition. PMID- 1284896 TI - Immunoelectrophoretic study on common antigens of Sao Lourenco da Mata and Belo Horizonte strains of Schistosoma mansoni adult worms and Biomphalaria snails. AB - Immunoelectrophoretic studies on common antigens were carried out by using rabbits sera immunized against Sao Lourenco da Mata and Belo Horizonte strains of Schistosoma mansoni adult worms and antigens of Biomphalaria glabrata pigmented (Jaboatao--PE); B. glabrata albino (Belo Horizonte--MG) and B. straminea (Sao Lourenco da Mata, PE). Furthermore, the reverse approach was proceeded, namely, sera anti Biomphalaria snails produced in rabbits were tested against both strains of Schistosoma adult worm antigens. The analysis of the common antigens between the SLM strains of S. mansoni adult worm and B. glabrata pigmented showed 8 to 9 precipitin bands, 3 bands with B. glabrata albino and only 1 band with B. straminea crude extracts. On the other hand, the BH strain of S. mansoni adult worm antisera produced 6 to 7 bands with B. glabrata pigmented, 5 bands with B. glabrata albino and 1 band with B. straminea antigenic extract. Biomphalaria snails crude extracts were fractionated by Sephadex G-100 column and three fractions were collected from each snail strain. The fractions were tested with anti SLM and BH strains of S. mansoni adult worm sera by immunoelectrophoresis. The common antigens fractionated from Biomphalaria snails crude extracts and those found for both strains of S. mansoni adult worm mostly existed in the first fraction and they were estimated to have molecular weight over 158,000 daltons. In our laboratory, it was found a relationship between the antigenic similarities and experimental infection rates of S. mansoni towards Biomphalaria snails so that more bands were seen with increasing infection rates of S. mansoni. PMID- 1284897 TI - Bacteriocin-like antagonism in Yersinia enterocolitica. AB - A total of 121 Yersinia enterocolitica O3 isolates from patients with gastroenteritis and 37 Y. enterocolitica reference strains with different O antigens were tested for bacteriocine production and sensitivity. By using cross streaking method strains belonging to serogroups of O5; O7,8; O7,13; O11; O11,23; O13,27; O17; O19,8 and O34 produced bacteriocin-like substances. None of the Y. enterocolitica O3 strains produced bacteriocin-like material and most of them were uniformly sensitive against the bacteriocin-like material produced by strains of serogroups O7,8; O7,13; O13,27 and O19,8. By sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) significant differences were demonstrated in the whole cell protein patterns of Y. enterocolitica reference strains belonging to different serogroups in the range of 33-47 kilodalton (kDa). Out of the ten examined bacteriocin-like material producer strains only one strain harboured a plasmid of about 60 megadalton (MDa). PMID- 1284898 TI - [Patient rights in clinical experimentation and medical practice]. PMID- 1284899 TI - [Antibodies against the rubella virus, cytomegalovirus and Toxoplasma gondii in a sample of women of childbearing age]. PMID- 1284900 TI - [Anti-HCV antibodies in i.v. drug-dependent prisoners under serological surveillance for HIV]. PMID- 1284901 TI - [The possible risks of transmission of hematogenous viroses in a prison community]. PMID- 1284902 TI - [The qualitative control of milk as food by the determination of lipopolysaccharides and bacterial ATP]. PMID- 1284903 TI - [The health and hygiene aspects in the management of dialysis services]. PMID- 1284904 TI - [The environmental conditions of an operating room: the problems and proposals]. PMID- 1284905 TI - General principles of laboratory methods for virus detection in environmental samples. PMID- 1284906 TI - Food as enteric viruses vehicle. PMID- 1284907 TI - [Current research trends in the hygiene field: a 5-year review of 4 Italian journals in the field]. PMID- 1284908 TI - [The effect of glycosaminoglycans in the pulmonary interstitial fibrosis development]. AB - The pulmonary interstitial fibrosis was caused by injecting Bleomycin into mouse trachea. After the injection, the volume of glycosaminoglycans (GAG) in bronchoalveolar lavage fluid and lung tissues was increased. The observation of histochemical stain and electron microscope showed that the distribution of GAG in lung tissues was varied at different time after the injection, and related to the volume of collagen proteins and the formation of pulmonary interstitial fibrosis. PMID- 1284909 TI - [The effect of mexiletine on theophylline pharmacokinetics in patients with bronchial asthma]. AB - Reported side effects of mexiletine, a useful drug for managing premature ventricular contractions (PVC) and ventricular tachycardia (VT), are gastrointestinal symptoms including nausea and vomiting. Theophylline, a bronchodilator, also causes similar gastrointestinal symptoms with its frequency proportional to the increases in its serum concentration. The occurrence of gastrointestinal symptoms is known to increase in combination therapy of mexiletine and theophylline. However, the pharmacokinetic interaction between mexiletine and theophylline has not been clarified. We, therefore, investigated the effects of mexiletine on theophylline pharmacokinetics. Three patients with bronchial asthma complicating PVC and/or VT (one male and 2 females, aged 70.0 +/ 13.1 years) were studied. All patients were given prophylactic theophylline anticipatory for asthmatic attacks, which was followed by oral administration of mexiletine, 200-300 mg daily, for PVC and/or VT. The serum theophylline concentrations in 3 cases were increased from 13.8 to 25.3 micrograms/ml, from 14.6 to 27.8 micrograms/ml, and from 10.4 to 15.4 micrograms/ml, respectively, after the administration of mexiletine. However, significant decreases in theophylline clearance were observed after the administration of mexiletine by 46, 47 and 35%, respectively. (p < 0.05) With a decrease in theophylline dosage, the serum theophylline concentrations decreased, and gastrointestinal symptoms resolved. Theophylline is metabolized mainly in the liver through an oxidative reaction of p-450 enzyme, however, its metabolism is affected by many factors, such as medications and complications. The results of this study indicated that mexiletine decreases the theophylline clearance by inhibiting the p-450 oxidative reaction to theophylline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284910 TI - [Recent trend in G-CSF therapy and clinical laboratory tests]. AB - Granulocyte colony-stimulating factor (G-CSF) has strong leukopoietic activity and it is used for patients with leukopenia during leukemia chemotherapy. However, some leukemia cells show a high affinity to G-CSF and are driven to proliferative phase. In our laboratory, we developed two testing methods. 1) Flow cytometric method on G-CSF susceptibility of leukemia cells using FITC-labeled G CSF, and 2) Immunohistochemical method for detecting the ratio of cells driven from dormant phase to proliferative phase by G-CSF with anti-PCNA antibody and Ki 67 antibody. In MDS patients G-CSF administration induced an increase of cells in proliferative phase. The patients treated with cytosine arabinoside following G CSF showed hematologically good improvement. A new mode of therapy using G-CSF in combination with other cytokines or antileukemic agents will be developed in the near future for treatment of leukemia patients. PMID- 1284912 TI - [The effects of retinoic acid and recombinant human granulocyte colony stimulating factor on alkaline phosphatase activity of HL-60 cells]. AB - We examined alkaline phosphatase (ALP) activity in the HL-60 cell induced by retinoic acid (RA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF induced a small but significant increase of NBT-reducing ability and ALP activity of the HL-60 cells. Among various inducers of cell differentiation, 1,25(OH)2D3 and dimethylsulfoxide (DMSO) caused the increase of the NBT-reducing ability and the suppression of ALP activity induced by rhG-CSF, while RA enhanced both of them. Protein kinase C inhibitors (H-7 and staurosporine) but not a protein kinase A inhibitor (HA1004) significantly suppressed the ALP activity induced by the simultaneous treatment with RA and rhG CSF. PMID- 1284911 TI - [Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human central nervous tumors]. AB - A silver colloid staining technique for identifying nucleolar organizer region associated proteins (Ag-NORs) was applied to 17 primary gliomas and 16 meningiomas. These comprised 8 glioblastomas, one pleomorphic xanthoastrocytoma, 8 benign astrocytoma, 10 nonrecurrent meningiomas and 6 recurrent meningiomas, in which the mean number of Ag-NORs' per nuclei, were 3.37, 2.34, 2.57, 2.16 and 2.80 respectively, identifying significant differences among these groups. Ag NORs of four giant cell glioblastomas showed low numbers of Ag-NORs, suggesting better prognosis. In spite of the time consuming and complicated counting method Ag-NORs is reproductive and useful as a tool for estimating the proliferating potential of various brain tumors, and appears to widely applicable in clinical laboratories. PMID- 1284913 TI - [The clinical usefulness of a new (the second generation) antibody to hepatitis C virus]. AB - To clarify the clinical usefulness of a second generation antibody to hepatitis C virus (anti-HCV-2), we tested the anti-HCV-2 by enzyme immunosorbent assay (Imucheck HCV Ab) in comparison to the first generation antibody (anti-HCV-1). Serum samples were obtained from the patients with acute hepatitis, chronic liver diseases, alcoholic liver disease and autoimmune liver diseases. Furthermore, both antibodies were tested in serum samples from individuals in a hyperendemic area of non-A, non-B hepatitis. Anti-HCV-2 was detected earlier than anti-HCV-1 in acute type C hepatitis. The prevalence of anti-HCV-2 was higher than that of anti-HCV-1 in acute and chronic non-A, non-B liver diseases. However, prevalence of anti-HCV-2 was not increased in patients with non-viral liver disease such as pure alcoholic liver disease and autoimmune liver diseases. The HCV-infection rate was increased to about 40% by detection of anti-HCV-2 in individuals in hyperendemic area of non-A, non-B hepatitis. Thus, the assay of anti-HCV-2 is very useful to detect actual HCV infection. The accuracy and sensitivity of anti HCV-2 were higher than those of anti-HCV-1. PMID- 1284914 TI - [The significance of the determination of AFP-isoform in the early diagnosis of hepatocellular carcinoma]. AB - To evaluate the significance of the determination of the AFP-isoform in the early diagnosis of hepatocellular carcinoma (HCC), the AFP-isoform was determined in 48 patients with HCC and in 53 patients with liver cirrhosis, using the lectin electrophoresis of AFP by antibody-affinity blotting technique. 1. The HCC-type AFP-isoform was detected in 44 of the 48 patients with HCC, 2. In about 30% of the patients with HCC, the HCC-type AFP-isoform appeared 3-10 months before the graphic diagnosis of HCC, 3. In about 60% of the patients with liver cirrhosis found to have the HCC-type AFP-isoform, HCC developed within one year. Thus, the serial determination of the AFP-isoform in patients with liver cirrhosis was considered very useful for the early diagnosis of HCC. PMID- 1284915 TI - [Coagulation and fibrinolysis in pregnancy]. AB - We studied on coagulation and fibrinolysis systems during pregnancy by measuring plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), fibrinogen/fibrin degradation products (FDP), plasminogen (PLG) and antithrombin III (AT-III). Ninety seven pregnant, 5 post delivery and 32 nonpregnant women aged from 20 to 52 years old were included in this study. Plasma concentrations of TAT and PIC in nonpregnant women were 3.38 +/- 1.02 micrograms/l and 0.65 +/- 0.24 micrograms/ml, respectively. TAT gradually increased with the progression of pregnancy and rapidly decreased after the delivery. Whereas PIC and AT-III concentrations did not change significantly during pregnancy. Fibrinogen, PLG and FDP concentrations changed similarly as TAT. Eight pregnants whose plasma PIC concentrations elevated more than 1.0 micrograms/l were further examined. In 6 women out of them (71.5%), FDP concentrations were elevated. In this particular group of subjects, however, they delivered normally without complications such as toxemia. These observations suggest that, at least, a hypercoagulative state progresses with pregnancy, being normalized after the delivery. Although we could not find the relationship between the hypercoagulation and clinical complications such as thrombosis and toxemia of pregnancy, present findings suggest that special caution should be paid on the pregnants whose TAT and FDP levels are elevated. PMID- 1284916 TI - [Detection of anti-HCV antibody, anti-GOR antibody and autoantibodies in sera of patients with non-A, non-B liver diseases]. AB - Anti-HCV antibody, anti-GOR antibody and autoantibodies were measured in sera of 41 patients with non-A, non-B liver diseases. Anti-HCV antibody (C100-3) was positive in 73.1% of the patients. On the other hand, anti-GOR antibody, rheumatoid factor, anti-ssDNA antibody and anti-dsDNA antibody was positive in 56%, 26.8%, 12.1% and 2.4% of the patients, respectively. In 70.7% of the patients, at least one of these four antibodies was positive. No relationship was observed in both positive rate and antibody titers among these different antibodies. On the other hand, positive rates of anti-HCV and anti-GOR antibody were higher in patients with persistently elevated serum ALT. Anti-GOR antibody appears to be a kind of autoantibody since it recognizes liver cell protein which has amino acid sequence partly similar to an epitope of HCV protein. Therefore, it could be speculated that the frequent appearance of antibodies against self constituents may be related to the chronic inflammation of the liver induced by HCV infection. PMID- 1284917 TI - [Primary adenocarcinoma of the duodenum: a clinical case and review of the literature]. AB - A case of primary duodenal adenocarcinoma recently observed gives the Authors the chance to review the literature. Diagnosis is often delayed because symptomatology is usually vague and non specific, a fact that is even more in contrast with diagnostic techniques, which, on the contrary, are handy and easily performed (endoscopy, duodenography). Surgical resection is the only proposable treatment while no local and distant diffusion has yet showed, otherwise the operation is limited to a digestive and/or biliary derivation. Anyhow, prognosis remains severe. PMID- 1284918 TI - [Carcinoma of the gallbladder. Our experience]. AB - A series of 11 patients (3 males and 8 females, mean age 63.4 yrs.) suffering from gallbladder cancer has been reviewed. Authors' purpose in reviewing their experience was to identify factors either in patient characteristics or treatment, that may influence statistic data. Symptoms, signs, laboratory and imaging studies were uniformly unhelpful in determining the diagnosis. Early diagnosis at a stage amenable to surgical excision remains the only therapeutical possibility. PMID- 1284919 TI - Blockade of potassium or calcium channels provokes modifications in TRH-induced TSH release from rat perifused pituitaries. AB - The aim of the present study was to determine the functional relationship between blockade of potassium or calcium channel activity and the initial burst of TSH secretion in response to TRH. Perifused rat pituitary fragments were stimulated by a 6-min pulse of physiological concentration of TRH (10 nM) in the presence or absence of pharmacological blockers of K+ or Ca2+ channels. Blockade of Ca(2+) activated K+ channels with TEA (10 mM and 30 mM), apamin (200 nM), or charybdotoxin (50 nM) completely or partially blunted TRH-induced TSH release. By contrast, blockade of voltage-dependent K+ channels with 4-aminopyridine (4-AP) (500 microM) or with dendrotoxin (DTX) (350 nM) significantly increased TSH response. Moreover, blockade of T-type voltage-sensitive Ca2+ channels (VSCC) with NiCl (3 mM) or with diphenylhydantoin (100 microM) significantly (P < 0.01) reduced TSH response to TRH, whereas blockade of L-type Ca2+ channels with verapamil (50 microM) was ineffective. Our results suggest that secretion of TSH in response to nanomolar concentrations of TRH is correlated with stimulation of Ca(2+)-activated K+ channels, and inhibition of 4-AP-and DTX-sensitive voltage dependent K+ channels; furthermore TSH response seems to depend on the activation of T-type VSCC. PMID- 1284920 TI - [Use of bacterial toximeters with separate cell cultures for continuous water monitoring]. AB - Two commercially available bacterial toxicity monitors are compared. As test organisms pure cultures of Pseudomonas putida are used in both systems. The bacteria are grown continuously in turbidostatic ("Toxalarm", LAR, Berlin, Germany) or chemostatic ("Stiptox-norm", Siepmann und Teutscher, Gross-Umstadt, Germany) regulated cultures in a selective culture medium in nonsterile devices. Toxic substances can be detected by continuously working bacterial respiration tests. Oxygen consumption is the measuring parameter. The bacterial test suspension is mixed continuously in a fixed proportion with air-saturated test water in a measuring cell. The separate culturing of the bacteria and the carrying out of the tests ensures that neither the bacterial culture is endangered by toxic substances nor the sensitivity can be changed by poison adaptation. Results of "Toxalarm"-tests with several chemicals (e.g. Atrazine, Lindane, 2-Nitro-phenol, Sodiumpentachlorophenolate) are presented. The registration of an alarm event (River Rhine) by "Stiptox-norm" is shown. PMID- 1284921 TI - [A biotest for water monitoring based on delayed fluorescence of algae]. PMID- 1284922 TI - [Valve movement of the mussel Dreissena polymorpha as a monitoring system for bodies of water]. AB - A new biological "early warning system" for continuous water control is presented that is based on the valve movements of the freshwater mussel Dreissena polymorpha. For two groups of up to 42 mussels, both the percentage of open mussels and the number of valve movements during a time interval are used to describe the activity behaviour of the zebra mussel. A main prerequisite of such a biomonitor should be the knowledge of the "normal" behaviour in correlation to changing environmental conditions. Preliminary results in Dreissena demonstrate the influence of the temperature, the daily cycle of light and the food concentration on both characteristics of the activity pattern. During toxicity tests, the mussels reacted significantly within 3-30 minutes after the addition of a toxicant. This was normally observed by both the decrease of the percentage of open mussels and the increase of the number of valve movements. Therefore--and against the background of the well-known "normal" behaviour--reliable limits for the detection of a harassing event can be defined. First experiments with Pentachlorophenol, Lindane, Atrazine and 2-Nitrophenol demonstrated to some extent a higher sensitivity compared to other "early warning systems". PMID- 1284923 TI - Circannual analysis of pineal gland indoles and vasotocin-like immunoreactivity in male rats kept on constant photoschedules and temperature. AB - Levels of vasotocin-like immunoreactivity (iVT) and the indoles serotonin (5HT), 5-hydroxyindole acetic acid, N-acetyl-serotonin (NAS) and melatonin were measured over 24-hour periods at monthly intervals in the pineal gland of male rats kept under constant laboratory conditions of photoperiod and temperature. The 8- to 10 fold increase in pineal iVT, which occurred during mid-August, was not related to variations over the 24-hour light:dark (L:D) cycle. Tryptophan and 5HT exhibited seasonal variations over the 24 h L:D cycle with a single peak during the winter months. Twenty-four-hour levels of NAS tended to increase during the fall and spring. Seasonal effects on indole metabolism were further suggested by a marked decline during the fall in the correlation between NAS versus melatonin in individual pineal glands. Positive correlations between 5HT versus NAS and 5HT versus melatonin tended to be significant only during the summer months. These data suggest that environmental cues other than photo-period and temperature can regulate pineal neuroendocrine functions. PMID- 1284924 TI - Pertussis toxin stimulates the secretion of [Met5]-enkephalin and the expression of proenkephalin A mRNA in bovine adrenal medullary chromaffin cells. AB - [Met5]-Enkephalin (ME) secretion and the expression of proenkephalin A (proENK) mRNA were studied following long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to pertussis toxin. Treatment with pertussis toxin for 24 h increased the secretion of ME in a concentration- and time-dependent manner. The magnitude of ME secretion continued to increase with time in the presence of pertussis toxin. The intracellular concentration of ME in the pertussis toxin treated group was not significantly different from controls, suggesting that elevated levels of ME secretion result from increased biosynthesis of ME rather than from release of stored ME. Prolonged (24 h) stimulation of BAMC cells with pertussis toxin also increased proENK gene expression. Pretreatment with nimodipine (a calcium channel blocker) and calmidazolium (a calmodulin antagonist) inhibited both the secretion of ME and the increase in proENK mRNA levels induced by pertussis toxin, while the intracellular calcium antagonist dantrolene and the protein kinase C inhibitors sphingosine and H7 [1-(5 isoquinolinylsulfonyl)-2-methylpiperazine] were ineffective in blocking pertussis toxin-induced responses. Forskolin (an adenyl cyclase activator) and isobutyl methyl xanthine (a phosphodiesterase inhibitor) increased both ME secretion and proENK mRNA levels; pertussis toxin synergistically increased the secretion of ME with these cyclic AMP-elevating agents but had only an additive effect with these agents on the level of proENK mRNA. Our results suggest that a pertussis toxin sensitive G protein may tonically regulate the secretion of ME as well as the level of proENK mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284925 TI - The virology and serology of hepatitis: an overview. AB - At least five viruses are recognised as causes of acute hepatitis which, in some instances, can develop into chronic disease. The viruses of hepatitis A (HAV) and hepatitis E (HEV) are spread predominantly by the faecal-oral route, whereas hepatitis B, C and D viruses (HBV, HCV and HDV) are spread by blood and other body fluids. The incubation period ranges from about four weeks for HAV to three months for HBV. The diagnosis mainly depends on the detection of various serological markers. The control of infection in the United Kingdom has been facilitated by the introduction of vaccines for HAV and HBV and screening blood for HBV and HCV. Good hygiene and sanitation, the availability of sterile equipment, and measures to modify the behaviour of high-risk groups such as injecting drug users, are also important in the prevention and control of viral hepatitis. PMID- 1284926 TI - The epidemiology and control of hepatitis A. AB - Hepatitis A virus (HAV) infection is endemic in developing countries and remains a public health problem elsewhere. A total of 7430 cases was notified in England and Wales in 1991. Children and young adults were most frequently affected. Risk factors include travel to countries of high endemicity, contact with an infected person and shellfish consumption. Person-to-person spread is common within families, closely knit communities and schools (especially nurseries). The provision of safe water and sanitary disposal of faeces are prerequisites for control of HAV throughout the world. In developed countries, human normal immunoglobulin (HNIG) is used for post-exposure prophylaxis and is given to those travelling abroad prior to possible exposure. Recommendations for the use of hepatitis A vaccine have have recently been made but it is expensive. Further studies on risk factors for infection, and on the efficacy of hepatitis A vaccine in outbreak control, are needed. PMID- 1284928 TI - Food poisoning at a wedding reception. PMID- 1284927 TI - The diagnosis and management of viral hepatitis. AB - Recent developments make it possible to identify the causative virus in most cases of acute and chronic viral hepatitis. Improvements in supportive care and the availability of hepatic transplantation have considerably reduced mortality for the fulminant forms of acute viral hepatitis, and advances in antiviral therapy have led to the possibility of cure for some patients with chronic viral hepatitis and improvement for many others. Algorithms are presented as a guide to the diagnosis and management of acute and chronic viral hepatitis. PMID- 1284929 TI - Food poisoning at a religious event. PMID- 1284930 TI - Food poisoning in two homes for the elderly. PMID- 1284931 TI - A pilot study of dried blood spot testing for HIV antibody in neonates. AB - An unlinked anonymous HIV antibody study of neonates, using surplus dried blood spots on Guthrie cards, was introduced as a means of estimating the prevalence of HIV infection in childbearing women. From March 1990 to February 1992, blood spots from 14,520 infants were tested for anti-HIV, using an HIV IgG antibody capture particle-adherence test; only one sample gave a confirmed positive reaction. This type of study involves no interference in routine care and can be operated without difficulty in a district general hospital setting where neonatal metabolic screening is performed. PMID- 1284932 TI - Performance assessment of neonatal dried blood spot testing for HIV antibody. AB - A study was undertaken to assess the performance of laboratories participating in the UK unlinked anonymised neonatal screening programme for the detection of HIV antibody. A coded panel of 100 contrived dried blood spots prepared form well characterised anti-HIV-1 and anti-HIV-2 positive sera and an anti-HIV negative serum was distributed to eight testing centres. Fifty-one out of 52 anti-HIV-1 positive samples were identified by all eight laboratories: five laboratories identified all 52 specimens. Only one laboratory detected all four anti-HIV-2 positive spots. None of the laboratories reported a seronegative spot as reactive. The sensitivity of anonymised neonatal anti-HIV-1 screening was deemed satisfactory in all participating laboratories but the margin of sensitivity was insufficient to allow pooling of dried blood spot eluates before testing. Technical modifications would be necessary to increase sensitivity for anti-HIV-2 were HIV-2 infection to be reported more frequently in the UK. Performance assessment of the screening programme should be repeated at regular intervals. PMID- 1284933 TI - Legionnaires' disease surveillance: England and Wales, 1991. AB - One hundred and eleven cases of legionnaires' disease were reported in England and Wales in 1991, a smaller total than in any year since reporting began in the late 1970s. Four cases were hospital acquired and a further nine may have been associated with a hospital stay. Nosocomial legionellosis remains a cause for concern. Fifty-two cases were associated with travel abroad. PMID- 1284934 TI - 'COVER' (cover of vaccination evaluated rapidly): 23. PMID- 1284935 TI - The surveillance and control of campylobacter infection. AB - Campylobacter jejuni and C. coli are the most commonly reported bacterial causes of enteritis in man in the United Kingdom. The reported incidence of campylobacter infection varies with place and time. Its epidemiology differs from that of salmonella: campylobacters do not multiply on food, secondary spread is rare, and infections peak at the end of May (salmonellas peak in July). Known sources of infection include poultry, milk, water, pets and other domestic animals. Campylobacters are widespread in the environment, and in domestic and wild birds and mammals. About 10% of infections reported in the UK are acquired abroad. The application of preventive measures can be effective in reducing the incidence of infection and its not inconsiderable financial burden. PMID- 1284936 TI - A case of ciprofloxacin-resistant typhoid fever. PMID- 1284937 TI - Vero cytotoxin-producing Escherichia coli O 157 in the United Kingdom. AB - A total of 226 cultures of Vero cytotoxin-producing Escherichia coli O 157 isolated from humans was received by the PHLS Laboratory of Enteric Pathogens during the six month period January to June 1992. A record monthly total of 122 isolates was received in June. Ten phage types (PT) were identified during this period; PT 2 (45%) and PT 49 (21%) predominated. In addition, 27 human sera with antibodies to E. coli O 157 lipopolysaccharide (LPS) were examined from other cases during this period, making a total of 253 cases of infection associated with E. coli O 157. PMID- 1284938 TI - Listeriosis surveillance: 1991. AB - A total of 130 cases of listeriosis was reported in England, Wales and Northern Ireland in 1991. This represents a slight increase on the 1990 total of 118 reports but a marked decline compared with the peak incidence of reporting of 291 in 1988, which was part of an upsurge of cases between 1987 and mid 1989. Two epidemiological features of note in 1991 were the reappearance of a late summer autumn peak in cases (commonly seen prior to 1987) and an increase in the number of reports among younger patients and children. The decline in listeriosis observed during the second half of 1989, which followed government health warnings about the consumption of pate, and the continued low level of reporting since 1989 may be due to the disappearance of a common food source. However, in the light of the recent outbreak of listeriosis in France it is important that diagnostic vigilance and warnings about high risk foods are maintained. PMID- 1284939 TI - The laboratory diagnosis of mycobacterial disease. AB - The diagnosis of mycobacterial disease still relies heavily on conventional microscopy and culture techniques. More modern methods, such as the Bactec 460 radiometric system and the Roche biphasic system, are becoming available but are not yet widely used. Non-culture methods eg, using molecular biology techniques or gas liquid chromatography, are being developed but are currently the province of research and reference laboratories. Disease caused by species other than Mycobacterium tuberculosis poses problems of diagnosis and treatment. These other species can be identified by comparatively simple techniques but, as they are widely distributed in the environment, deciding between casual contamination and true infection can be difficult. Although such infections are not a major problem in numerical terms, the variable response of patients to treatment means that conventional sensitivity testing is of little assistance, and it is necessary to seek evidence of synergy in drug combinations for the effective treatment of these infections. PMID- 1284940 TI - Leprosy surveillance. PMID- 1284941 TI - Food safety: the HACCP approach to hazard control. AB - The Hazard Analysis Critical Control Point (HACCP) approach is becoming increasingly recognised as a valuable means of identifying and controlling hazards in the food production process, and thereby ensuring that food reaching the consumer is safe. The central feature of HACCP analysis is the determination of critical control points (CCPs)--those stages in the process which must be controlled to ensure the safety of the product. Once identified, a monitoring system is set up for each CCP to ensure that correct procedures are maintained and actions taken if CCP criteria are not achieved. The chief advantage of HACCP is that it is proactive; it aims to prevent problems occurring. Although HACCP is most readily applied to manufacturing processes, attempts are being made to adapt the system to other sectors of the food industry, such as catering. PMID- 1284943 TI - Cholera update. PMID- 1284942 TI - Exposure to hepatitis B virus: guidance on post-exposure prophylaxis. PHLS Hepatitis Subcommittee. AB - This paper summarises the views of the PHLS Hepatitis Subcommittee on prophylaxis after exposure to known and potential sources of hepatitis B virus (HBV) at work and in the community, and expands on the guidance on hepatitis B immunisation and the prevention of occupational exposure to blood given elsewhere. It defines significant exposure and gives guidance on incident recording, risk assessment, testing and storage of incident-related blood specimens and follow-up. It recommends that HBV prophylaxis should be determined by assessment of the likely infectivity of the source and of the HBV status of the person exposed. PMID- 1284945 TI - Computer viruses: prevention is better than cure. PMID- 1284944 TI - Global surveillance of tuberculosis. PMID- 1284946 TI - Legionnaires' disease in Corfu. PMID- 1284947 TI - Salmonella mikawasima. PMID- 1284948 TI - The viral causes of AIDS. PMID- 1284949 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1284950 TI - The diagnosis of SRSV infection. PMID- 1284951 TI - A nosocomial outbreak of parvovirus B19 infection. PMID- 1284952 TI - Vitamin D3, its receptor and regulation of epidermal keratin gene expression. AB - Among extrinsic modulators of keratinization are certain hormones and vitamins, which makes them potentially important pharmacological tools for treatment of keratinization disorders. Vitamin D3 and vitamin A, and their metabolites, promote and inhibit keratinization, respectively. We have shown that retinoic acid, via its nuclear receptor, directly suppresses the expression of the keratin genes which are markers of keratinocyte differentiation. Here we present evidence that 1,25(OH)2 vitamin D3 and its nuclear receptor do not directly regulate keratin gene expression. Co-transfection of a vector expressing the nuclear receptor for vitamin D3 with responder DNA constructs containing keratin gene promoters had no effect on the level of activity of keratin gene promoters either in the presence or in the absence of vitamin D3. We conclude that vitamin D3, unlike retinoic acid, modifies keratin synthesis indirectly, by changing the differentiation phenotype of the keratinocyte. PMID- 1284953 TI - Changes in type I keratin expression associated with HPV16 transformation of human epidermal keratinocytes. AB - We have used immunoblotting to compare expression of type I keratins in two strains of normal human epidermal keratinocytes (v and u) and their HPV16 transformed derivatives (vp and up). The levels of keratins 14 and 17 were similar in all four cell strains, whereas keratins 18 and 19 were more abundant in vp and up than in the normal parental keratinocytes. Keratin 13 was more abundant in the transformed cells than in the parentals; in addition, expression in v was higher than in u, and expression in vp was higher than in up, suggesting strain-specific variation in expression. Keratin 16 was the only keratin to be more highly expressed in v and u than in vp and up; this is consistent with the reduced capacity of the transformants for stratification and terminal differentiation. Double-label immunofluorescence of vp and up showed that more cells expressed involucrin than keratin 16. We conclude that HPV16 transformation results in marked changes in keratin expression. The increased expression of keratin 18, a keratin that is normally expressed in simple epithelia, fits well with reports of increased keratin 18 expression in invasive squamous cell carcinomas of skin and other keratinocyte-derived tumours. PMID- 1284954 TI - Patterns of phenotypic expression of human junctional, gingival and reduced enamel epithelia in vivo and in vitro. AB - Epithelia differ regionally in their patterns of phenotypic expression. The junctional epithelium (JE) that attaches the oral mucosa to the teeth is a unique tissue that shows a pattern of differentiation unlike other oral epithelia and forms basal lamina against the non-vital tooth surface. The mechanisms that establish this unusual phenotype and the developmental origin of this epithelium are both uncertain. The formation of JE by downgrowth of the oral gingival epithelium (OGE) during tooth eruption has been suggested but morphological studies indicate that it may be derived from the reduced enamel epithelium (REE) that covers the crown of the unerupted tooth. These epithelia of potential origin differ in their developmental histories: intrinsic differences between them could thus significantly influence the phenotype of an epithelium formed from them. The patterns of phenotypic expression of specimens of dissected JE, OGE and REE, and of cell cultures of these epithelia grown under standardized conditions, were examined (1) by immunocytochemistry using monoclonal antibodies with specificity for individual cytokeratins, vimentin and ICAM-1, and (2) by two-dimensional SDS PAGE and immunoblotting. The results indicated that, in vivo, OGE expressed keratin markers typical of differentiating mucosal epithelium; JE and REE, in contrast, lacked expression of most such markers but expressed keratins typical of simple epithelia together with some undefined keratin peptides. All epithelia showed changes in vitro but OGE remained different from JE and REE. OGE lost expression of the differentiation markers K1, K10 and K13; it acquired some expression of K19, but less than JE and REE. Cultures of JE and REE retained some expression of ICAM-1 and K8 and K18, and consistently acquired high levels of vimentin expression. These findings indicate that differences persist in standardized culture conditions and that these are apparently of an intrinsic nature. They support a concept of the origins of JE from REE and suggest that the unusual in vivo phenotype of JE results partly from intrinsic differences acquired during its development. PMID- 1284955 TI - Irreversible inhibition of transglutaminases by sulfonium methylketones: optimization of specificity and potency with omega-aminoacyl spacers. AB - Sulfonium methylketones, of structure Cbz-Phe-NH(CH2)nCOCH2S+ (CH3)2, n > 2, are specific and potent inactivators of transglutaminases. The length of the -(CH2)n spacer moiety, n = 1-5, is a critical determinant for both the specificity and potency of the inactivator. The dipeptidyl analog Cbz-Phe-Gly-(CH2)nS+ (CH3)2, n = 1, is a more powerful inactivator of the thiol proteinase cathepsin B, k/K > 3 x 10(5) M-1 min-1, than of transglutaminases, ki(app)/Ki(app) < 1.5 x 10(4) M-1 min-1. In contrast, the gamma-aminobutyryl analog, n = 3, is a very potent transglutaminase inactivator with ki(app)/Ki(app) = 3.1 x 10(6) M-1 min-1, but does not inactivate cathepsin B. In cell studies, the gamma-aminobutyryl and epsilon-aminohexyl analogs inhibited the transglutaminase-mediated process of ionophore-induced cross-linked envelope formation by human malignant keratinocytes and the order of potency was related to that found for enzyme inhibition. The sulfonium methylketones, in equilibrium with the resonance stabilized ylides, are chemically inert towards glutathione under ambient conditions demonstrating the potential utility of this novel class of transglutaminase inhibitors for the study of enzyme inhibition in cellular environments. PMID- 1284956 TI - Inactivation of gamma-aminobutyric acid aminotransferase by various amine buffers. AB - It is hypothesized that buffers capable of forming a Schiff base with the PLP of gamma-aminobutyric acid aminotransferase (GABA-AT) may lead to denaturation and inactivation of the enzyme. On the basis of this hypothesis three new methods for the selective destruction of GABA-AT in GABAse (a commercial bacterial source of a mixture of GABA-AT and succinic semialdehyde dehydrogenase [SSDH]) and from pig brain are described: (1) dialysis against a primary or secondary amine buffer; (2) gel filtration with a primary or secondary amine buffer as eluent; (3) inactivation with gabaculine followed by dialysis or gel filtration with pyrophosphate buffer. The SSDH activity in GABAse, which remains unchanged by all of these methods, may then be used in a coupled assay to measure the activity of GABA-AT from different sources. These results also suggest that the use of primary and secondary amine buffers should be avoided when inhibitors are being tested with GABA-AT. PMID- 1284957 TI - Studies on aldose reductase inhibitors from fungi. I. Citrinin and related benzopyran derivatives. AB - The fungal metabolites, citrinin (4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6- oxo-3H 2-benzopyran-7-carboxylic acid) and DHMI (3,4-dihydro-6-methoxy-3,7-dimethyl-1H-2 benzopyran-8-ol), as well as certain synthetic derivatives, have been evaluated for aldose reductase inhibitory activity using a rat lens enzyme preparation. Citrinin and its reduction product, dihydrocitrinin, were found to have significant activity (IC50 approximately 10 microM), whereas the other compounds were 3-10 times less potent. Kinetic studies showed that citrinin was not an irreversible inhibitor of the enzyme, as might be expected of a quinone methide. Spectroscopic (NMR) evidence is presented for the existence of citrinin predominantly in the form of its hemi-acetal in aqueous solutions, suggesting that it is this benzo[c]pyran derivative which interacts with the enzyme, rather than the quinone methide form. PMID- 1284958 TI - Hydroperoxidic inhibitor of horse liver alcohol dehydrogenase activity, tightly bound to the enzyme-NAD+ complex, characteristically degrades the coenzyme. AB - The strong inhibition of horse liver alcohol dehydrogenase (HLAD) by p methylbenzyl hydroperoxide (XyHP) is only transient, XyHP behaves also as a pseudo-substrate of the enzyme and in the presence of NAD+, is degraded by HLAD to (as yet unidentified) non-inhibiting products while the NAD+ is converted to a derivative similar to the "NADX", originally observed in an analogous reaction of HLAD with hydrogen peroxide. The apparent KM for XyHP is approximately 10(4) times smaller than that for H2O2. The catalytic constant kcat for HLAD degradation of XyHP is two orders of magnitude less than that for ethanol dehydrogenation. XyHP inhibits both directions of the alcohol-aldehyde interconversion with equal potency. The first step of the inhibition mechanism is a tight binding of XyHP to the binary HLAD-NAD+ complex. PMID- 1284959 TI - 4-(Aminomethyl)-1-aryl-2-pyrrolidinones, a new class of monoamine oxidase B inactivators. AB - Both 4-(aminomethyl)-1-phenyl-2-pyrrolidinone (4a) and 4-(aminomethyl)-1- (methoxyphenyl)-2-pyrrolidinone (4b) hydrochlorides were synthesized via a six step sequence, which represents a general approach to 1,4-disubstituted 2 pyrrolidinones. Both of these compounds inactivated monoamine oxidase B and represent the first in a new class of monomamine oxidase inactivators. PMID- 1284960 TI - Ferrocenopapain, an organometallic protein formed by site-specific inactivation of papain using chloroacetylferrocene. AB - Papain is rapidly, specifically and irreversibly inactivated by chloroacetylferrocene in a time-dependent, two-stage process which involves initial, physical complexation between the enzyme and the organometallic reagent followed by chemical reaction. The kinetics of the process show saturation kinetics with respect to inactivator concentration. The modification occurs with a 1:1 stoichiometry and the degree of loss of enzymatic activity is directly reflected in the loss of thiol groups in the active-site that are accessible to Ellman's reagent. The modification is faster at higher pH. The ferrocenium ion of the modified papain can be generated at low pH by anaerobic treatment with ferric nitrate and shows a 180 percent increased lifetime at pH 3.3 compared to the acetylferrocenium ion under identical conditions. The spectral properties of the ferrocenopapain indicate that the ferrocene is in an unusual environment at the protein active-site and the implications of this are discussed. PMID- 1284961 TI - Time-dependent inhibition of pea cotyledon diamine oxidase by some hydrazides. AB - The inhibition of diamine oxidase (EC 1.4.3.6) from pea cotyledons (PDAO) by some hydrazides has been studied. It was found that PDAO is inhibited in a time dependent manner at pH = 7.0 by the hydrazides of acetic, benzoic, nicotinic, isonicotinic, picolinic and 3,4-dihydro-4-oxophtalazine-1-carboxylic acids, by 1 (carboxymethyl)trimethylammonium chloride hydrazide (Girard's reagent T), 1 (carboxymethyl)pyridinium chloride hydrazide (Girard's reagent P) and oxalic acid dihydrazide. The inhibition was partially reversible. Rate constants for enzyme inactivation were in the range 0.29-1.95 min-1. The hydrazides give apparent noncompetitive inhibition at pH = 7.0, but for isonicotinic hydrazide, this changes to competitive inhibition at pH = 8.0. Apparent inhibition constants (K1APP) for the hydrazides with PDAO are in the range 0.005-1.5 mmol l-1. PMID- 1284962 TI - Observations on the conformational changes in the structure of a cell surface protease, followed by its ability to be recognised by competitive and non competitive inhibitors. AB - Lung tumour cells possess a cell surface protease which can be inhibited by a cytoplasmic protein inhibitor extracted from these cells. The dissociation of this enzyme-inhibitor complex on the surface of tumour cells in sections treated with 10(-4) M sodium dodecyl sulphate has been studied. The dissociation of the inhibitor and regain of enzymic activity was followed by the use of a fluorescent probe which binds to the active centre of the cell surface enzyme in a competitive manner. PMID- 1284963 TI - Additional peptidyl diazomethyl ketones, including biotinyl derivatives, which affinity-label calpain and related cysteinyl proteinases. AB - Calpain, the calcium-activated cysteinyl proteinase, can be irreversibly inactivated by peptidyl diazomethyl ketones in which the peptide portion contains a penultimate leucine residue. Some new derivatives of this type have been synthesized and examined for their rates of inactivation of chicken gizzard and human platelet calpain. Two derivatives containing a C-terminal biotin residue, Biot-Aca-Leu-TyrCHN2 and Biot-Aca-Leu-Leu-TyrCHN2, have also been prepared in the expectation that their application to the study of the function of calpain and related proteases will prove fruitful. PMID- 1284964 TI - Exploring the hexokinase glucose binding site through correlation analysis and molecular modeling of glucosamine inhibitors. AB - A series of N-substituted glucosamines has been designed, synthesized, and tested as inhibitors of yeast hexokinase. All derivatives exhibited competitive inhibition kinetics with respect to glucose. Quantitative structure-activity relationships were derived from the resulting inhibition data. The most significant equation demonstrated the existence of highly specific steric effects for the seven meta-substituted benzoylglucosamines included in the relationship. Molecular modeling of potential complexes between the inhibitors and the hexokinase substrate binding site strongly suggests that the steric effects arise from potential contacts with two amino acid residues lying in the region occupied by the amide substituents. PMID- 1284965 TI - Cholinesterase studies with (R) (+)- and (S)(-)-5-(1,3,3-trimethylindolinyl)-N-(1 phenylethyl)carbamate. AB - A limited number of carbamates have been found useful for treatment of cholinergic symptoms with pyridostigmine and physostigmine being the main focus. In recent years 5-(1,3,3-trimethylindolinyl)N,N-dimethylcarbamate (I) has received considerable attention in the Chinese literature for a similar role. We report on the first synthesis of stereoisomers of an analog of (I). The isomers prepared were (R)(+)-5-(1,3,3-trimethylindolinyl)-N-(1-phenylethyl)carbamate (II) and (S)(-)-5-(1,3,3-trimethylindolinyl)-N-(1-phenylethyl)carbamate (III). The pKa value for each isomer was 6.8. Eel acetylcholinesterase inhibition studies were carried out at 25.0 degrees C over the pH range of 6.0 to 9.0. They reflect the first pH profiles using enantiomorphs of a cholinesterase inhibitor. The inhibition potencies for (II) and (III) over the range examined were similar. At pH 7.60 the ki for II = 7.38 x 10(3) M-1 min-1 (SD = 398) and for (III) the ki = 6.67 x 10(3) M-1 min-1 (SD = 355). In accord with the findings of Wilson and Bergmann20 on physostigmine our results indicate that the protonated form of (II) and (III) is the more potent inhibitor. PMID- 1284966 TI - Biochemical characterisation of a pancreatic elastase inhibitor from the leech Hirudinaria manillensis. AB - The jawed leech, Hirudinaria manillensis is closely related to Hirudo medicinalis, both belonging to the same family Arhynchobdellida. From Hirudo, two potent peptide inhibitors, hirudin (a thrombin inhibitor) and eglin (an elastase/chymotrypsin inhibitor) have been characterised in detail. During our studies to isolate thrombin inhibitor from the leech Hirudinaria a potent inhibitor, analogous to eglin, was also detected. Results indicate that this inhibitor, which we have named 'GELIN', is significantly different from eglin. Gelin was isolated and purified to homogeneity by ion exchange chromatography and reverse phase HPLC. The isoelectric point of Gelin was estimated to be 4.55, in contrast to 6.45 for eglin. The molecular weight of Gelin was similar to eglin, as estimated by SDS-PAGE. Amino-terminal sequence analysis of the first 29 residues show no sequence homology with eglin or any other serine protease inhibitors. Circular dichroism studies showed that the secondary structure of Gelin has no helix, 58% beta sheets and 42% random structures compared to 19% helix, 56% beta sheets and 25% random structures in eglin. Like eglin, Gelin inhibits elastase, cathepsin G and chymotrypsin but has little or no activity towards plasmin, thrombin, pepsin and trypsin. These data suggest that the elastase inhibitors from these two species of leech are fundamentally different in structure, indicative of independent evolutionary origin. PMID- 1284967 TI - Observations on the inhibition of serum and cell surface enzymes by eicosapentaenoic acid. AB - The relationship between serum and tumour cell surface proteolytic enzymes and the development of muscle breakdown in cancer cachexia has been studied in a murine model of the condition (MAC16). The surface of the MAC16 tumour cells carried a proteolytic enzyme referred to as guanidinobenzoatase (GB). Serum from mice also contained an enzyme (referred to as MSE) which cleaved the trypsin inhibitor 4-methylumbelliferyl-p-guanidinobenzoate as a true substrate, but there was no relationship with weight loss or the presence or absence of tumour and the level of this serum enzyme. Polyunsaturated fatty acids (PUFAs) were shown to be inhibitors of MSE at microM concentrations and one PUFA, eicosapentaenoic acid (EPA) was found to be a non-competitive inhibitor of both MSE and GB. The effect of EPA was specific since other proteolytic enzymes, trypsin, esterase and tissue plasminogen activator were unaffected by concentrations inhibiting GB and MSE. MSE and GB are two different enzymes which possess some common properties. However, GB is likely to be significant for tumour development since MSE is also found in normal mouse serum. PMID- 1284968 TI - Some 1-, and 3-substituted 3-(4'-aminophenyl)pyrrolidine-2,5-diones as selective inhibitors of aromatase. AB - 1-Alkyl-3-(4'aminophenyl)pyrrolidine-2,5-diones (7,R = C3H7-C7H15) are potent inhibitors of aromatase in vitro, the 1-hexyl (Ki = 62nM) being about 100-fold more potent than aminoglutethimide (AG), and more selective in their ratio of aromatase:CSCC inhibitory potency. The 1-pentyl, 1-hexyl and 1-heptyl derivatives are more stable to liver microsomal metabolism in vitro than AG possibly due to inhibition of the liver cytochrome P450s. 1,3-Dialkyl-3(4' aminophenyl)pyrrolidine-2,5-diones (9) have been synthesised by a novel method. Although the higher homologues (di-pentyl and di-hexyl) are more potent in vitro as inhibitors of aromatase than AG, they are less active than their 1-alkyl counterparts with the same alkyl substituent. PMID- 1284969 TI - Inhibition of human synovial beta-glucuronidase by steroidal compounds. PMID- 1284970 TI - Blood serum angiotensin-converting enzyme, alfa2-macroglobulin and triglycerides in patients with diabetes. AB - Blood serum activity of ACE, alfa2-macroglobulin as well as triglycerides concentration was determined in 90 patients with diabetes and in 40 healthy persons. Taking into account criteria established by WHO the patients with diabetes were divided into two groups. The first group consisted of 32 patients with diabetes of type I (juvenile one); the second group consisted of 58 patients with diabetes of type II (adult one). It was found that blood serum level of all tested parameters is statistically increased (p < or = 0.001) in comparison with control group. In patients with diabetes of type I the level of alfa2 macroglobulin and ACE was higher than in those with diabetes of type II. The serum contents of triglycerides in both groups of patients was comparable. No correlation between parameters determined in patients with diabetes was found. PMID- 1284971 TI - [Variants of the Kato-Katz method used in the diagnosis of experimental schistosomiasis]. PMID- 1284972 TI - Evidence for commissurally projecting parvalbumin-immunoreactive basket cells in the dentate gyrus of the rat. AB - The fluorescent retrograde tracer, fluorogold, was used to identify commissurally projecting neurons in the hippocampus and dentate gyrus. After injection of fluorogold into the hippocampus, the contralateral hippocampus was evaluated for fluorogold-immunoreactive or fluorescent neurons. In addition to observing labeled hilar neurons and CA3 pyramidal cells that previously have been reported to send commissurally projecting axons to the contralateral hippocampus, the authors unexpectedly found a population of fluorogold-labeled cells in the granule cell layer with the morphology and location of GABA-immunoreactive basket cells. Immunocytochemical staining revealed that all fluorogold-labeled cells of the granule cell layer were immunoreactive for parvalbumin. However, not all parvalbumin cells, shown previously to be a subset of GABA neurons, were fluorogold-labeled. The association between fluorogold transport and parvalbumin immunoreactivity was unique for these cells of the granule cell layer. In the adjacent hilus, relatively few of the many fluorogold-labeled cells were parvalbumin- or GABA-immunoreactive. These results (1) identify a population of presumed inhibitory neurons that apparently form commissural projections; (2) document that all of these cells contain the calcium-binding protein parvalbumin; and (3) indicate that the vast majority of commissurally projecting hilar neurons are neither parvalbumin- nor GABA-immunoreactive. PMID- 1284973 TI - Tracing of axonal connections by rhodamine-dextran-amine in the rat hippocampal entorhinal cortex slice preparation. AB - In order to demonstrate axonal connections preserved in rat temporal cortex slices the authors used rhodamine-dextran-amine as a tracer. The slices contained the neocortical areas Te2 and Te3, the medial and lateral entorhinal cortices (MEC and LEC), the subicular regions, and the dentate gyrus and hippocampus proper. Rhodamine-dextran-amine crystals were placed by microinjection into a given area. Following this local lesioning the dye was permitted to diffuse and migrate intraaxonally in antero- and retrograde directions for about 8 hours. The slices were then formaldehyde-fixed and analyzed by fluorescence microscopy. Most of the known connections within and between the entorhinal cortex and the hippocampus and dentate gyrus were preserved in the slice preparation, provided that the slices were cut with a near horizontal orientation corresponding to plates 99-108 in Paxinos and Watson (1986). Only the lateral perforant path between the LEC and the hippocampus could not be followed to its full extent. The authors conclude that most aspects of the intrinsic synaptic organization of the temporal lobe can be reliably studied in hippocampal-entorhinal cortex slice preparations. PMID- 1284974 TI - Lesion-induced synapse reorganization in the hippocampus of cats: sprouting of entorhinal, commissural/associational, and mossy fiber projections after unilateral entorhinal cortex lesions, with comments on the normal organization of these pathways. AB - This study evaluates whether three forms of sprouting occur in the hippocampus of the cat following unilateral entorhinal cortex (EC) lesions: (1) sprouting of projections from the EC contralateral to the lesion; (2) sprouting of the commissural/associational system; and (3) sprouting of mossy fibers. Tract tracing techniques were used to define the normal organization of the entorhinal cortical projection system, the commissural/associational (C/A) systems, and the mossy fiber projections in normal cats. The same techniques were then used to evaluate whether there were changes in these projections in animals with long standing unilateral EC lesions. The projections from the entorhinal cortex were evaluated autoradiographically following injections of 3H proline into the entorhinal area. The projections of the C/A system were traced using the Fink Heimer technique after lesions of the hippocampal commissures, and by using autoradiographic techniques after injections of 3H proline into the hippocampus. The distribution of mossy fibers was evaluated using the Timm's stain. The results reveal that unilateral lesions of the EC in cats lead to the same sorts of sprouting that have been described in rats. There is: (1) an increase in the density of the crossed projection from the surviving EC to the contralateral dentate gyrus that had been deprived of its normal EC inputs; (2) an expansion of the terminal field of the C/A projection system into portions of the molecular layer of the dentate gyrus normally occupied by EC projections; and (3) an increase in supragranular mossy fibers in some animals. The mossy fiber sprouting was especially prominent when the lesions encroached upon the hippocampus. The studies also reveal additional details about the normal organization of hippocampal pathways in cats. The most important points are: (1) there is a crossed projection from the entorhinal cortex to the contralateral dentate gyrus; and (2) there is a complex laminar organization of the commissural and associational terminal fields in the molecular layer of the dentate gyrus that appears to be related to the point of origin of the projections along the septotemporal axis of the hippocampus. This heretofore unrecognized aspect of the laminar organization of C/A terminations has important implications for the temporal competition hypothesis, which has been advanced to account for the development of these afferent systems. PMID- 1284975 TI - Mossy cell axonal projections to the dentate gyrus molecular layer in the rat hippocampal slice. AB - The ipsilateral associational pathway connects different septotemporal levels of the dentate gyrus. Neurons of the dentate hilus project hundreds of micrometers from the cells of origin to the inner molecular layer. The authors hypothesized that mossy cells, the major cell type of the hilus, also project locally to the inner molecular layer. Within a 400 microns slice, mossy cells were (1) recorded intracellularly while the inner molecular layer was stimulated to test for antidromic responses, and (2) labeled with biocytin and examined with light and electron microscopy for axonal projections into the molecular layer. The authors found that mossy cells can be antidromically activated by inner molecular layer stimulation and that axonal projections to the molecular layer can be visualized within a 400 microns hippocampal slice. In 13 of 19 intracellularly labeled and electrophysiologically characterized mossy cells, collaterals could be traced into the molecular layer. These results suggest that mossy cells contribute to the ipsilateral associational pathway and also participate in local recurrent circuitry to influence granule cell activity. PMID- 1284976 TI - Region-specific age effects on AMPA sensitivity: electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1. AB - The effects of aging on the responsiveness of hippocampal neurons to iontophoretic application of L-glutamate and AMPA were studied in vitro. There were no effects of age on neuronal responses to L-glutamate; however, CA1 pyramidal cells of old rats, but not granule cells in the fascia dentata, showed both a smaller reduction in extracellularly-recorded synaptic responses following application of AMPA (presumably mediated by depolarization), and smaller extracellular "DC" fields (measured by subtracting the DC potentials at the dendrite and soma following AMPA application in the dendrites). To examine the cellular bases of this age-related alteration in AMPA sensitivity, two additional electrophysiological approaches were used: (1) measurement of the amplitude ratios of extracellular EPSP and fiber potential components of the Schaffer collateral-CA1 response; (2) measurement of intracellularly recorded unitary EPSPs and quantal analysis of their fluctuations. The interpretations that would be placed on four hypothetical possible outcomes of such experiments are outlined and assessed in relation to the experimental data. The pattern of results obtained in the present experiments supports the following conclusions: In old rats, individual Schaffer collateral synapses do not appear to have altered AMPA receptor properties, as neither the mean size of the unitary synaptic response nor the apparent quantal size differs between age groups; however, the data do support the conclusion that there are fewer synapses per Schaffer collateral branch in old versus young CA1 pyramidal cells. PMID- 1284977 TI - Bv: a distinct category of B sub-group among Chinese blood donors in Hong Kong. AB - During the period 1984-1989, a total of 46 examples of Bv phenotype were encountered out of a total of 567,210 donors, giving an incidence of 1 in 12,330 among the Chinese in Hong Kong. The Bv determinant corresponds to the portion of the B antigen that is present on rabbit red cells, and gives a negative reaction with polyclonal anti-B reagents absorbed with rabbit red cells that still react with B3. Some potent monoclonal anti-B reagents confirm the absence of a B epitope from Bv red cells even by adsorption and elution techniques. The failure of some monoclonal anti-B reagents to detect Bv demonstrates the need to select or blend monoclonal anti-B reagents for use in typing Oriental bloods. Cell conversion techniques failed to convert O cells to B cells using Bv serum with the appropriate substrate, whereas sera from most of the other B variants were capable of doing so. The Bv phenotype, therefore, represents a distinct category of B subgroups that is easily distinguishable from B3 and other B variants. PMID- 1284979 TI - Differences in the characteristics of human monoclonal and polyclonal anti-D as revealed by immunochemical investigations: human monoclonal antibodies share specificities with natural antibodies. AB - To determine the basis of the tissue cross-reactions shown by some human monoclonal anti-Rh D antibodies, we have investigated the tissue reactivities of 48 further human monoclonal antibodies (mAb) against D and other Rh antigens, and compared them with those of normal and anti-D sera and immunoglobulin preparations, and affinity-purified polyclonal anti-D antibodies. Although we were unable to detect any tissue reactivities associated with the D-binding fraction of polyclonal antisera or prophylactic immunoglobulin, the non-erythroid cell types identified by the tissue-reactive human anti-Rh mAb of both IgM and IgG class were those recognized by antibodies present in both normal and anti-D sera. These results indicate: (a) that the tissue specificities of human anti-Rh mAb are similar to those of natural antibodies, and (b) that there are immunochemical differences between polyclonal and monoclonal anti-D antibodies, at least of IgG class, which may be relevant to the use of the latter in the prevention of haemolytic disease of the new-born by immune prophylaxis. PMID- 1284978 TI - Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia. AB - Eighteen cases of alloimmune neonatal neutropenia (ANN) were analysed for their clinical and serological properties. Pregnancy was normal in all cases, but a 50% incidence of abortion is recorded. With the exception of two premature babies, all newborns were delivered at term. Omphalitis and mild infections of the skin were predominantly present. None of the new-borns died by overwhelming sepsis. The average duration of neutropenia was 11 weeks (range 3-28 weeks). Intravenous IgG therapy was followed by transient remission in 2 of 4 affected newborns. Antibody differentiation revealed in five sera NA1-, in four sera NA2- and in two sera NB1-specific antibodies. In two sera only HLA antibodies were detectable. Complement activating antibodies were determined in 72% of the sera. Screening for granulocyte-specific antibodies in 1016 postpartum sera of unselected women revealed a total of 11 sera (1.1%) reacting selectively with granulocytes, but only four (0.4%) were directed against a known granulocyte-specific antigen. None of the new-born of mothers alloimmunized to granulocyte antigens developed neutropenia, which suggests an incidence of ANN below 0.1%. PMID- 1284980 TI - Serum concentration of alpha-2-macroglobulin, alpha-1-antitrypsin and alpha-1 antichymotrypsin [correction of alpha-2-antichymotrypsin] in patients with Hodgkin's disease. AB - In twenty four patients diagnosed with Hodgkin's disease we have determined several antiproteases. Our findings have shown the decrease of concentration of alpha-2-macroglobulin and increase of alpha-1-proteinase inhibitor and alpha-1 antichymotrypsin. The observed changes were statistically significant p < 0.001. We did not find any correlation between the concentration of inhibitors and the clinical stage of carcinoma and histopathological data. The determination of the level of antiproteases in patients with cancer disease may be assumed to reflect partly at least the capability of anticancer mechanism in the host. PMID- 1284981 TI - [Granulosa cell tumor with liver metastasis treated with partial hepatectomy and chemotherapy. Report of a case]. AB - A patient with granulosa cell tumor recurrence 14 years after primary resection, was treated with partial hepatectomy and adjuvant chemotherapy (vinblastine, cisplatin and bleomycin). She achieved complete remission and is free of disease 18 months after treatment. PMID- 1284983 TI - Antibody to hepatitis C virus in 1,305 Italian multiply transfused thalassaemics: a comparison of first and second generation tests. Cooleycare Group. PMID- 1284982 TI - The effect of glycosylation trimming enzyme inhibitors on monoclonal antibody recognition of alpha-sialoglycoprotein epitopes. AB - The human erythrocyte membrane contains four sialoglycoproteins, denoted alpha, beta, gamma and delta (also known as glycophorins A, C, D and B respectively), of which alpha-sialoglycoprotein (alpha-SGP) is the most predominant species. The extracellular portion of alpha-SGP is heavily glycosylated with approximately 15 O-linked carbohydrate side-chains and a single N-linked group. We have used inhibitors of carbohydrate trimming enzymes to investigate the contribution of this single N-glycan moiety towards the recognition of a range of antibody binding sites on alpha-SGP. Two erythromyeloid cell lines, K562 and HEL, were cultured in the presence of these inhibitors and altered binding of antibodies to epitopes adjacent to the N-glycan was observed. Digoxigenin-coupled lectins were used to stain cytocentrifuge preparations and Western blots of cell lysates in order to confirm that modification of N-linked carbohydrate side-chains had been achieved. We suggest that the N-glycan side chain of alpha-SGP has a role in conferring conformational stability upon epitopes which lie in its vicinity. PMID- 1284984 TI - Antibody binding to blood group antigens in relation to temperature: scanning electron microscopy of immunogold-labelled erythrocytes. AB - Binding patterns of mouse monoclonal antibodies (mAb) to P1, Pk, N, I, H, Y or A antigens were visualized in the backscatter electron imaging mode of a scanning electron microscope by indirect immunogold labelling. Experiments were performed at room temperature (RT) and at 4 degrees C. In experiments with anti-P1 and anti Pk, clusters of immunolabelling particles dominated the immunolabelling pattern much more at RT than at 4 degrees C. By contrast, no clustering was seen with anti-N, even at RT. Clustering was also observed at RT with anti-I, anti-H and anti-Y, and on some Ax and A3 cells with anti-A, but was much reduced at 4 degrees C. Immunolabelling was stronger at 4 degrees C than at RT with all mAb except anti-N and anti-A. The results indicate that glycolipid blood group antigens are more mobile in the membrane of intact erythrocytes at RT than at 4 degrees C, and that the cells bind more antibodies to such antigens at 4 degrees C than at RT. We suggest that antigen immobilization in the cold will reduce cross-linking of antigens and hence increase the number of antibody molecules needed for epitope saturation, leading to increased binding of antibody in the cold. This may be the main reason for cold-enhanced agglutination with human blood group antibodies. PMID- 1284985 TI - [Specific odor component produced by Mycobacterium lepraemurium on Ogawa yolk medium]. AB - When Mycobacterium lepraemurium is grown on the 1% Ogawa yolk medium, it produces a specific odor. This odor was not observed in other easily cultivable acid-fast bacilli. Therefore, identification of the components responsible for the specific odor produced by M. lepraemurium was attempted. The odor components were extracted for overnight with sterilized and distilled water from the Ogawa yolk medium on which M. lepraemurium had been cultivated for two months. The odor components in the extract was adsorbed on refined charcoal. After washing with distilled water for three times, the charcoal was dried. Then the odor components were eluted from the charcoal with ethanol and the eluate was condensed under nitrogen gas flow at 40 degrees C. The condensate was analyzed by Gas Chromatography-Mass-Spectrum (GC-MS). Phenylethanol and phenylacetic acid were identified as major odor components. A mixture of authentic phenylacetic acid, its methyl and ethyl esters, smelled similar to the odor of cultivated medium of M. lepraemurium. Thus, phenylacetic acid was identified as the key odor component produced by M. lepraemurium. When initial isolation culture of M. lepraemurium from murine leproma was cultivated on the Ogawa yolk medium by adding phenylacetic acid, growth inhibition was brought by the compound. PMID- 1284986 TI - [Modification of Harada's method for rapid staining of mycobacteria]. AB - Harada employed periodic acid-carbol pararosaniline and periodic acid-methenamine silver stain for demonstrating chromophobic bacilli which do not get stained with conventional carbol fuchsin or counter stain. This staining method takes considerable time for complete oxidation with periodic acid. We have succeeded in reducing the oxidation time by using hydrogen peroxide treatment prior to periodic acid and with the use of acidified sodium hydrogen sulfite treatment before carbol pararosaniline stain. We also found that in methenamine silver stain, combined use of semicarbazide and microwave treatment can shorten the whole staining time up to four hours without losing ito sensitivity. PMID- 1284987 TI - Hepatitis C virus in Pune, India. PMID- 1284988 TI - Some biological properties of the human amniotic membrane interferon. AB - Human amniotic interferon was investigated to define the species specificity of its antiviral action and to compare its anti-cellular and NK cell stimulating activities with those of other human interferons. The antiviral effect was titrated in bovine (RV-IAL) and monkey (VERO) cells. Amniotic interferon exhibited, in bovine cells, 5% of the activity seen in monkey cells, while alpha interferon displayed 200%. No effect was detected with either beta or gamma interferon in bovine cells. Daudi cells were exposed to different concentrations of various interferons and the cell numbers were determined. The anticellular effect of the amniotic interferon reached its peak on the third day of incubation. Results suggested a higher activity for alpha and gamma interferons and a lower activity for beta when compared to amniotic interferon. Using total mononuclear cells as effector cells and K 562 as target cells in a 51Cr release assay, it was demonstrated that low concentrations of amniotic interferon consistently stimulated NK cell activity in cells derived from several donors, the results indicating a higher level of activity with this interferon than with alpha and beta interferons. PMID- 1284990 TI - Antigenic differences among Leishmania amazonensis isolates and their relationship with distinct clinical forms of the disease. AB - Immunoblot analysis was used to investigate antigenic differences among clinical isolates of Leishmania amazonensis and their role in the etiology of the disease. Western blots of promastigote homogenates were analyzed with either monoclonal antibodies (MAbs) specific for the L. mexicana complex (M-4, M-6, M-9, and M-11) or polyclonal sera from L. amazonensis infected patients with the various forms of clinical disease. In the case of the MAbs, no significant variation was observed among the strains of L. amazonensis, isolated from cases of cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffuse cutaneous leishmaniasis (DCL), visceral leishmaniasis (VL) or post kala-azar dermal leishmaniasis (PKDL), in either the relative mobility (Mr) or the quantitative amount (intensity) of the antigenic determinants. In the case of the sera of the infected patients, the patterns of antigenic reactivity of these strains revealed that, despite showing the presence of shared antigens, differences were observed between some of the antigenic components of the various isolates of L. amazonensis that were recognized by a single serum. Differences were also demonstrated between the antigenic determinants of a single isolate of L. amazonensis that were recognized by the different patients' sera. No apparent association was consistently found, however, between the Mr components identified in these isolates and the clinical form of the disease or the geographical area of isolation. In addition, the spectrum of antigens recognized by the sera from patients with the same clinical form were not identical; although in some instances, similar Mr antigens were shared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1284989 TI - Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria. AB - In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weight ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection, in parallel to the parasitaemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen induced) stimulation of antigen-specific cells rather than a generalized non specific (mitogen-induced) triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that the polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation. PMID- 1284991 TI - Susceptibility of Simulium (Chirostilbia) pertinax Kollar, 1832 (Diptera, Simuliidae) to Bacillus thuringiensis var. israelensis in an atypical breeding habitat. PMID- 1284992 TI - [Role of interferon in neuropsychiatric diseases]. PMID- 1284993 TI - [Experimental approaches to treatment of prostatic adenoma with the luliberin analog surfagon]. AB - Therapeutic efficacy of surfagon, an analog of LH-RH which was injected subcutaneously at a daily dose of 100 micrograms/kg for 30 days, was investigated in ACI male rats with induced prostatic adenoma. This drug was shown to be effective proceeding from a morphological study and measurement of the prostate. Measurement of blood testosterone levels by radioimmunoassay showed a decrease in this level in rats, treated with surfagon, i. e. a therapeutic effect of the drug in prostatic adenoma was accompanied by a decrease in the level of androgens. PMID- 1284994 TI - Pivotal role of hepatocellular regeneration in the ultimate hepatotoxicity of CCl4 in chlordecone-, mirex-, or phenobarbital-pretreated rats. AB - Our earlier histomorphometric and biochemical studies suggested that the progressive phase of the interactive toxicity of chlordecone (CD) + CCl4 involves suppression of hepatocellular regeneration. The objective of the present work was to correlate hepatocellular regeneration with CCl4 (100 microliters/kg)-induced hepatotoxicity in rats maintained for 15 days on a normal (N) diet, relative to the regenerative response in rats maintained on a diet containing either 10 ppm CD, 225 ppm phenobarbital (PB), or 10 ppm mirex (M). Hepatocellular regeneration was assessed by measuring DNA and 3H-thymidine (3H-T) incorporation, followed by autoradiographic analysis of liver sections. Hepatotoxicity was assessed by measuring plasma transaminases (aspartate and alanine) followed by histopathological observations of liver sections for necrotic, swollen, and lipid laden cells. Lethality studies were also carried out to assess the consequence of hepatotoxicity on animal survival. Dietary 10 ppm CD potentiated the hepatotoxicity of CCl4 to a greater extent than PB or M, as evidenced by elevations in plasma enzymes. Although the serum enzymes were significantly elevated in PB rats in contrast to the slight elevations in N and M rats, they returned to normal levels by 96 hr. However, serum enzyme elevations in CD rats were progressive with time until death of the animals. Actual liver injury by CCl4 was greater in PB- than in CD-pretreated rats, as evidenced by histopathological observations. A 100% mortality occurred in CD-pretreated rats at 60 hr after CCl4 administration, whereas no mortality occurred in either N-, M , or PB-pretreated rats, indicating recovery from liver injury. Hepatocellular nuclear DNA levels were significantly decreased starting at 6 hr after CCl4 administration to CD-pretreated rats, but not in M- or PB-pretreated rats. 3H-T incorporation into nuclear DNA as well as percentage of labeled cells showed a biphasic increase in N rats: 1 at 1-2 hr, and the other at 36-48 hr after CCl4 administration. However, only 1 peak of 3H-T incorporation at 36-48 hr was observed in the CD + CCl4 combination, which was also significantly lower when compared to that observed after the M or PB + CCl4 combination treatments. These findings suggest that there is recovery in N-, PB-, or M-pretreated rats from CCl4-induced injury by virtue of the stimulated hepatocellular regeneration and tissue repair.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1284995 TI - [Neurological lesions of the premature infant]. PMID- 1284996 TI - [The prognosis of prematurity]. PMID- 1284997 TI - Effects of tracer, volume, osmolarity and infection on fluid kinetics during CAPD. AB - A review is given on various aspects of using the disappearance rate of intraperitoneally administered macromolecules for the determination of fluid kinetics in CAPD patients. The rationale and mathematics for the calculation of transcapillary ultrafiltration and of indirect measurement of lymphatic absorption are described. A comparison is made between autologous haemoglobin, human albumin and dextran 70. Dextran 70 appeared most useful; one brand of human albumin increased solute transport. Lymphatic absorption was higher after the installation of a 3-litre dialysate volume than after a 2-litre one, and also higher during peritonitis than after recovery from infection. A gradual increase in intraperitoneal volume, as obtained with glucose 3.86% dialysate, had no apparent effect on the disappearance rate of dextran 70. It is concluded that intraperitoneally administered dextran 70 is a clinically useful marker for the description of fluid kinetics in CAPD patients under various conditions. PMID- 1284998 TI - Use of the disappearance rate for the estimation of lymphatic absorption during CAPD. AB - Several studies are discussed which investigated the usefulness of the disappearance rate of macromolecules from the peritoneal cavity for estimating convective fluid loss from the peritoneal cavity into the peritoneal lymphatic system. It is shown that dextrans are removed from the peritoneal cavity by a size-independent process at a mean rate of 1.37 +/- 0.15 ml/min, whereas the clearance from blood to dialysate of dextrans is size-dependent. The fluid removal rate estimated by the difference in bidirectional transport of inulin (1.79 +/- 0.38 ml/min; p < 0.0005) was of the same order of magnitude as has been found using the removal rate of macromolecules from the peritoneal cavity. Also, the role of local accumulation of macromolecules was studied during continuous administration of dextrans. No differences were found in the dextran disappearance rate before and after saturation of the peritoneal interstitium with dextran (1.1 +/- 0.6 vs. 1.0 +/- 0.4 ml/min). During a study using a hypoosmotic solution we calculated a net transcapillary backfiltration of fluid, whereas the dextran removal rate was in the same order of magnitude as found using commercially available dialysate. In our opinion, the disappearance rate of macromolecules is an estimate of convective fluid loss from the peritoneal cavity into the peritoneal lymphatic system. PMID- 1284999 TI - New concepts in the investigation and treatment of prostatic hyperplasia. PMID- 1285000 TI - Differentiating the language disorder in dementia from dysphasia--the potential of a screening test. AB - A considerable amount of information is now available about the way in which senile dementia of the Alzheimer type (SDAT) affects language performance. Speech and language therapists may have the requisite knowledge to work in the field, but they have few assessment materials to facilitate improved differential diagnosis between language breakdown in dementia and dysphasia. This study highlights the differential diagnostic potential of a short screening test with a weighted scoring system. The best discriminatory effect was in the areas of action picture description, verbal description and confrontation naming. Neither age nor sex appears to have a significant effect on results, and re-test results contribute little to the test's discriminatory power in terms of differential diagnosis between the two groups. The possibilities for future test usage and development are discussed. PMID- 1285001 TI - The influence of endotracheal bleomycin administration on phospholipid composition of rat lung surfactant. AB - The influence of intratracheal bleomycin instillation (10 mg x kg-1) on lung surfactant phospholipids in rats after 7 and 14 days from drug administration was evaluated. It was stated that bleomycin causes a great fall in phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol content, both in extra- and intracellular pool of surfactant. The data thus presented evidenced that intratracheal bleomycin administration caused a profound changes in the lipid composition of rat lung surfactant. PMID- 1285002 TI - The influence of endotracheally administered bleomycin on hydroxyproline content and collagenase and elastase activity in rat lungs. AB - The effect of endotracheal administration of bleomycin (10 mg x kg-1) on hydroxyproline content, and on collagenase and elastase activities in rat lungs was investigated. A significant increase in lung tissue hydroxyproline content on 7th day after bleomycin administration was observed. Similar rise in this amino acid level in bronchoalveolar lavage was observed, however, on 14th day after the drug administration. Collagenase activity was lowered by 17% and 36%, respectively. No changes in elastase activity were found. These data suggest that bleomycin cause the lung fibrosis by restraining the collagenase activity. PMID- 1285003 TI - Studies on tachykinin (neurokinin) receptor coupled with inositol phospholipid hydrolysis and salivation in rat salivary glands. AB - 3H-substance P binding to the membranes of rat salivary glands was studied. The Kd and Bmax values were found to be 0.34 nM and 141 fmole/mg protein respectively using established natural occurring tachykinins to displace the binding. The rank order of potency was identified as substance P > neurokinin A > neurokinin B. These natural occurring tachykinins stimulate inositol phospholipid hydrolysis in slices of rat salivary glands, and the rank order of potency was also substance P > neurokinin A > neurokinin B. When salivation was induced by natural occurring tachykinins and acetylcholine (via i.v. route) in anesthetized rats with doses eliciting equivalent salivating responses, atropine blocks acetylcholine- as well as neurokinin B-, but not substance P- or neurokinin A-induced salivation. Based on the results mentioned above, we make a tentative conclusion that multiple receptor subtypes of neurokinins may exist in rat salivary glands. The neurokinins B receptor subtype is likely located presynaptically in the cholinergic nerve endings, whereas substance P and/or neurokinin A receptor subtypes may exist in the glandular tissue. The salivation induced by these neurokinins is likely through the activation of receptors, which are coupled to phosphatidylinositol turnover pathway. PMID- 1285004 TI - Characterization of some biochemical properties of bradykinin-induced cAMP and cGMP formation in guinea pig ileum. AB - One of the receptor-mediated events, cyclic nucleotide, i.e. cAMP and cGMP formation induced by bradykinin in guinea pig ileum was investigated in this report. Bradykinin, similar to acetylcholine, produced a rapid rise in the levels of cAMP and cGMP in the ileum. The absolute amount of these cyclic nucleotides induced by the same dosages (10(-8) to 10(-6) M) of bradykinin was greater in cAMP than in cGMP. This increase in cyclic nucleotides was dependent upon the presence of calcium in the medium. Addition of EGTA (0.1 mM) in a calcium free medium resulted in a significant reduction of the levels. The elevation of cAMP and cGMP levels induced by bradykinin in the ileum could not be blocked by either atropine (an anticholinergic agent) or propranolol (a beta-adrenergic blocker). Both of these blockers did not alter the basal levels of two cyclic nucleotides. However bradykinin-induced cAMP formation could be completely blocked by either indomethacin (a prostaglandin synthesis inhibitor) or dexamethasone (a phospholipase A2 inhibitor), This, however, was not true in the case of bradykinin induced cGMP formation. Additionally, both blockers did not create a significant change in the basal levels of these cyclic nucleotides. Bradykinin induced cAMP formation in the ileum was indicated by observed results to likely occur through an indirect process, i.e. the formation and release of prostaglandin in the cell, whereas bradykinin-induced cGMP formation did not. The elevation of these cyclic nucleotides in the cells was observed to be related to the movement of calcium ion across the cell membrane. PMID- 1285006 TI - Veratridine-induced intoxication: an in vitro model for the characterization of anti-ischemic compounds? AB - Due to the complexity of ischemia-induced cellular dysfunction many different pharmacological approaches have been tested to improve cellular ischemia resistance. However, despite the importance of [Na+]i for ischemia-induced dysfunction, only very few studies have investigated the contribution of the Na+ channel to ischemia-induced failure of intracellular ion homeostasis. Since an activation of Na+ channels by veratridine also results in a failure of intracellular ion homeostasis, the veratridine- and ischemia-induced alterations of cellular function were compared. Moreover, despite the difference in the electrophysiological changes induced by veratridine and ischemia, the possible involvement of a slowly inactivating, less selective Na+ channel in both veratridine- and ischemia-induced cellular dysfunction is discussed. As a conclusion it is suggested that veratridine intoxication could be a helpful in vitro method for the characterization of putative anti-ischemic compounds. PMID- 1285005 TI - The motor actions of natural neurokinins and their specific agonists on the gastrointestinal tract of the rat. AB - Neurokinins (NK) are a group of peptides that share a common C-terminal and play an important role in control of the motor functions of the mammalian gut. Neurokinin receptors such as NK1, NK2 are certainly present in any segment of gut, whereas the NK3 receptors are probably present in the ileum of the Guinea pig and duodenum of the rat. We measured gastrointestinal responses with natural NK and their very specific agonists to determine the probable receptors in the stomach and small intestine of Sprague-Dawley rats. After overnight fasting, the rats were intubated with a catheter to feed saline liquid meal that contained 10% charcoal. Simultaneously, various doses of NK ranged selected from 10(-10) and 10(-7) mol kg-1 included substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [Nle10]-NKA4-10, senktide, and vehicle were intraperitoneally injected. At 15 min after being fed test meal, the rats were sacrificed. Then we removed entire gut including the stomach to measure the total length of small intestine and transit length of the charcoal, from which the transit ratio was calculated. In comparison with ratios of rats treated with vehicle, the inhibited transit ratios for charcoal were seen among SP at 10(-10) mol kg-1, NKA at 10( 10) and 10(-7) mol kg-1, [Nle10]-NKA4-10 at 10(-7) mol kg-1, and senktide at all doses except 10(-8) mol kg-1. Enhanced transit ratios were seen for septide at the doses 10(-8) and 10(-7) mol kg-1. Likewise the mean total intestinal lengths of rats if they received various treatments of peptides except that rats treated with NKB had somewhat diminished length than those of vehicle-treated rats. Some natural NK and their very specific receptor agonists mainly inhibited rat gastrointestinal charcoal transits. We suggest the probable presence of NK1, NK2 and NK3 receptors in the small intestine and stomach including pylorus of the rat. PMID- 1285007 TI - Pardaxin-stimulated calcium uptake in PC12 cells is blocked by cadmium and is not mediated by L-type calcium channels. AB - Pardaxin is an excitatory neurotoxin which triggers neurotransmitter release as a result of voltage-dependent pore formation within the neuronal membrane. We have used several pharmacological manipulations of calcium influx to characterize pardaxin pore activity in PC12 cells in culture. Pardaxin stimulates the uptake of radioactive calcium into PC12 cells in a dose dependent fashion (ED50 of 0.4 microM). This stimulation is partially inhibited by nifedipine, a blocker of L type calcium channels. Effective blockade of pardaxin stimulation was produced by the inorganic calcium channel blockers cadmium (IC50 of 10 microM) and nickel (2 mM). Homologous down regulation of L-calcium channels by the agonist Bay K-8644, inhibited the subsequent stimulation of calcium uptake by this drug, but not by pardaxin. A fluorometric analysis of pardaxin pore formation in unilamellar large liposomes indicates pardaxin pores are blocked by cadmium (10-200 microM). These data distinguish between pardaxin pores and L-type calcium channels in PC12 cells. We suggest pardaxin as a pharmacological ionophore tool to modulate neuronal calcium homeostasis and neurotransmitter release. PMID- 1285008 TI - RNA metabolism during the sexual differentiation of rat hypothalamus. AB - Modifications in the basal molecular biology parameters (total concentrations of RNA, DNA, proteins, rRNA, tRNa, free and polysomal bound poly-A+ mRNA) have been determined daily in the growing hypothalamus of male and female rats from day 1 to day 8 after birth. Changes observed in the parameters studied in this work occurred mainly in the first 48 h after birth. In males tRNA and free mRNA (f mRNA) contents decreased from day 1 to day 2 and then their concentrations remained more or less constant. Total mRNA significantly decreased from day 1 to day 3 and showed a further significant decrease from day 6 to day 8. Polysomal bound-mRNA (b-mRNA) decreased from day 1 to day 3, then increased to day 6, and finally decreased once more from day 6 to day 8. The b-mRNA/f-mRNA, mRNA/rRNA and mRNA/total RNA ratios showed a bimodal behavior with a first peak on day 2, and a second, smaller peak, on days 6-7. The changes observed in the females on the first 2-3 days of life were the inverse of those observed in the males, most of the parameters studied showed a sharp increase from day 1 to day 2 or to day 3 and then a drastic decrease. The only exception to this behavior was the b-mRNA/f mRNA ratio which showed a small decrease from day 1 to day 2, followed by a continuous increase from day 2 to day 8. b-mRNA concentrations, after the sharp decrease from day 2 to day 3 of life, increased from day 3 to day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285009 TI - Integration, expression and germ-line transmission of foreign growth hormone genes in medaka (Oryzias latipes). AB - Gene constructs consisting of human growth hormone (hGH) gene driven by promoter/regulatory sequence of mouse metallothionein (mMT), viral thymidine kinase (vTK), rat cholecystokinin (rCCK), or chicken beta-actin (cBA) gene were injected into the cytoplasm of fertilized medaka eggs via the micropyle. More than 49% of the injected embryos survived at hatching. Up to 26% of the survivors showed integration of the introduced gene construct, as determined by polymerase chain reaction analysis and subsequent confirmation by Southern blot hybridization of the genomic DNA. A significant fraction of F1 progeny, derived from crosses between transgenic founders and the nontransgenic individuals, inherited the transgene. Expression of hGH gene was also observed in some of the P1 founders and F1 transgenic progeny carrying mMT-hCG or cBA-hGH gene. Furthermore, the growth performance of the P1 mMT-hGH and cBA-hGH transgenic founders and F1 cBA-hGH F1 transgenic progeny was significantly greater than their full sibling, nontransgenic individuals. In addition to the microinjection experiment, a gene construct containing the long-terminal repeat (LTR) sequence of avian Rous sarcoma virus (RSV) and rainbow trout (rt) GH2 cDNA was introduced into embryos of medaka by electroporation using an exponential decay electroporator. Approximately 70% of the electroporated embryos survived at hatching, and 20% of the survived individuals integrated RSVLTR-rtGH2 cDNA into their genomes. These two techniques will greatly enhance the ability to study regulation of gene expression in transgenic animals during differentiation and development. PMID- 1285010 TI - Predictive markers for hepatitis C antibody ELISA specificity in Australian blood donors. AB - The hepatitis C antibody reactivity rate in 91,748 blood donors tested using the ORTHO HCV C-100 ELISA system was 0.51%. Specificity of ELISA positive reactions was measured using a recombinant immunoblot assay (RIBA). The aim of this study was to identify markers in ELISA positive donors which were predictive of a RIBA positive result. Samples from 430 ELISA positive donors were tested by the first generation RIBA, RIBA-1, which incorporates two HCV peptides C-100 and 5-1-1. Fifty-five per cent (236) were positive and 19% (83) indeterminate. Multivariate analysis of gender, age, HCV ELISA OD ratio, alanine aminotransferase (ALT) status and hepatitis B core antibody (anti-HBc) status identified age, magnitude of HCV ELISA OD ratio and anti-HBc status as the only independent predictors of a positive RIBA-1 result. The relative odds of being RIBA-1 positive were 4.6-fold (95% CI 1.3-16.4) higher among donors aged 25-34 years compared with donors less than 25 or greater than 44; 6.1-fold (2.1-17.9) higher if the donor was anti-HBc positive and 273.4-fold (30.9-2417) higher if the HCV ELISA OD ratio was greater than 5.98 compared to those with a ratio less than 1.77. Seventy-eight of the 83 RIBA-1 indeterminates were tested on the second generation RIBA, RIBA-2, which includes two additional HCV peptide, C22 and C33c. Thirty-one per cent (24) were positive and 41% (32) were negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285011 TI - Specificity and sensitivity of first and second generation anti-HCV ELISA in a low prevalence population. AB - Specificity and sensitivity of the second generation enzyme immunosorbent assay for hepatitis C antibodies were calculated from data on 208,554 blood donors screened with either the first or the second generation tests (ELISA I, ELISA II) or both (4,639 donors). The second generation ELISA was no more specific than the first generation test in this low-prevalence blood donor population (specificity 99.7% vs 99.6%). Most of the donors (93.5%) who were found to be reactive using ELISA II were negative or indeterminate according to a supplemental test, the second generation recombinant immunoblot assay (RIBA II). The second generation ELISA was found to be more sensitive than the first. It identified all 16 donors who were positive according to RIBA II during screening with ELISA I. The latter found only 13 out of 30 donors (43%) who were positive according to RIBA II during screening with ELISA II. If the number of RIBA II positive donors found during the first year of screening with ELISA I (74, 0.024%), and the number of RIBA II positive but ELISA I negative donors found during screening with ELISA II, are taken into consideration it can be estimated that the added sensitivity due to using ELISA II is about 40%. PMID- 1285012 TI - Transmission of HCV infection by RIBA indeterminate and positive blood units. AB - A retrospective study was carried out on the recipients of 73 units of blood from 53 donors found reactive for anti-HCV. The donors were screened with anti-HCV enzyme-linked immunosorbent assay (ELISA C-100) and reactivity was confirmed with the first generation recombinant immunoblot assay (RIBA I). Fifty-two patients were recipients of blood from donors reacting as RIBA I 'indeterminate' and 21 of blood from RIBA I 'positive' donors. Only three recipients (5.8%) from 'indeterminate' donors were anti-HCV positive indicating that such donors are very seldom infectious. Eleven (52.4%) recipients from 'positive' donors had antibodies to HCV, indicating that not all RIBA-positive donors are necessarily infectious. Pretransfusion samples of the seropositive recipients were unavailable. All samples were analyzed with the first generation ELISA and with either the second-generation ELISA or RIBA (RIBA II) in order to evaluate test sensitivity. RIBA II was more sensitive than RIB I. One RIBA I indeterminate donor was positive by RIBA II. His recipient had antibodies to HCV. Twelve RIBA I indeterminate and three RIBA I positive donors were negative by RIBA II. All their recipients were anti-HCV negative. The second-generation ELISA was also shown to be more sensitive than ELISA C-100. The second-generation ELISA detected six confirmed anti-HCV positive recipients who were negative by ELISA C-100. PMID- 1285013 TI - Viruses, chemotherapy and immunity. AB - An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression. The interdependence of host immunity with antiviral efficacy is underscored by the increased antiviral drug resistance in persons with advanced degrees of chronic immunosuppression, related to the higher level of viral replication and viraemia which occurs in the absence of an effective host immune response. Further definition of the precise mechanisms of these interactions should facilitate the rational design of antiviral agents and immunomodulatory therapies to improve treatment of viral infections. PMID- 1285014 TI - [The use of gentian violet for staining Trypanosoma cruzi in tissue]. PMID- 1285015 TI - Identification of a diverged octamer binding site important in the B cell specific expression of the CD20 gene. PMID- 1285016 TI - Corticosteroids are transcriptional regulators of acute inflammation. PMID- 1285017 TI - N-acetyl-cysteine is a potent suppressor of human immunodeficiency virus transcription in persistently infected cells. PMID- 1285018 TI - Immunohistochemical study on antigenic phenotype of Langerhans cell histiocytosis. AB - Immunohistochemical study on 26 cases of Langerhans cell histiocytosis (LCH) using several leukocyte antibodies in addition to traditionally used markers (S 100 protein and peanut agglutinin) revealed that the proliferating cells of LCH expressed UCHL1, MT1 as well as classically known positivity for S-100 protein, HLA-DR and peanut agglutinin but were negative for OPD4. In comparison to S-100 protein peanut agglutinin (PNA) using a two stage method produced weaker staining and positively stained cells were sparse. Also in this study, a small proportion of proliferating cells in LCH was observed to be reactive for both myeloid/macrophage antigens (KPI, MAC 387 and lysozyme) and Langerhans cell marker (S-100 protein), verifying the existence of a hybrid form of histiocytes. PMID- 1285019 TI - Impact of endothelial activation on fibrinolysis and local proteolysis in tissue repair. PMID- 1285020 TI - Accumulation of type 1 plasminogen activator inhibitor and vitronectin at sites of cellular necrosis and inflammation. PMID- 1285021 TI - Regulation of plasminogen activation in rat cell lines. AB - The regulation of plasminogen activators (PA) and their inhibitors (PAI) in the rat cell lines: HTC and L2 was studied. HTC plasminogen activator inhibitor type 1 (PAI-1) production was stimulated by dexamethasone, serum factors and insulin; that of tissue-type plasminogen activator (tPA) by cAMP raising agents. Retinoic acid, butyrate, phorbol ester and endotoxin did not affect net PA/PAI activity elaborated by HTC. L2 cells produced tPA, which production was stimulated by retinoic acid, phorbol myristate acetate, butyrate and cAMP; serum factors blunted their response, whereas in the synthetic serum substituting medium Ultraculture and with cocktail Ultroser the action of tPA stimulators was enhanced. PMID- 1285022 TI - Fibrin-specific fibrinolysis. PMID- 1285023 TI - Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1, and VCAM-1: pathological significance. PMID- 1285024 TI - Lysis of platelet-rich thrombi: the role of PAI-1. PMID- 1285025 TI - [Efficiency of inhibitors (phenylethanol, nalidixic acid, sodium azide)in the isolation of strictly anaerobic bacteria from a polymicrobial specimen]. AB - The efficacy of inhibitors (PEA, Ac Nal, Az de Na) in the isolation of strict anaerobes in polymicrobial sample. The efficacy of three inhibitors to select strict anaerobic bacteria in the polymicrobial sample had been studied. First step: The most frequent anaerobes encountered in the infections are isolated in the agar Columbia containing the different inhibitors. This step allowed us to check the inhibition of the germ we have to isolate. Next step: polymicrobial mixtures were made. The composition of which is very similar to the samples we receive in the laboratory. The swarming Proteus is the facultative anaerobic germ which gives us difficulties when isolating strict anaerobic bacteria. Then, the different mixtures were isolated separately in the agar in which the inhibitors were added. The plates containing Azide of Na and PEA gave us the best results. PMID- 1285026 TI - [Optimization of culture conditions for the production of Salmonella typhi O and H antigenic suspensions]. AB - A Behring's production protocol of antigenic suspensions O and H of Salmonella typhi has been studied. The object of this study has been the Search of optimal conditions of cultivation and their exploitation on fermentor. A fermentation using the I.P.A culture medium has been realized to compare its results with that obtained using Behring's culture medium (B.C.M). The optimal cultivation conditions obtained are a waving rate of 400 tr/mn, a pH of 7.6 and an important air flow. Relating to nutritious constituents, the adequate glucose concentration is about 8g/1 and it seems better to replace meat extract by yeast extract. Comparatively to I.P.A culture medium, one of the most important advantage of Behring's culture medium modified reside in the conservation of the antigenicity of Salmonella typhi. PMID- 1285027 TI - [Epidemiology of salmonella infections in Algeria. Evolution of the salmonella serovars isolated from 1986 to 1990]. AB - The serovars evolution of 3340 Salmonella strains isolated from 1986 to 1990 in Algeria have been studied. Among Salmonella responsible for typhoid-paratyphoid fevers, 98% are S. typhi; the prevalence of this serovar is observed every year. Among the other Salmonella, 50 different serovars have been isolated from 1986 to 1990. The predominant serovars change every year but 98% out of the total belong to 8 groups of Kauffmann White scheme; the most frequent are: groups O: 6, 7-O: 8 O: 4 and O: 9. PMID- 1285028 TI - Macroscopic and microscopic imaging of stable iodine (127I) in the thyroid. AB - The purpose of this review is to describe the two imaging methods which allow direct estimation of stable iodine (127I) within thyroid gland either in vivo by X-ray fluorescence or in vitro by secondary ion mass spectrometry (SISM) microscopy. X-ray fluorescence of thyroid is mainly used for the estimation of thyroid iodine content (TIC) in human pathophysiology. Although its measurement has little revelance for routine explorations of thyroid function, this is a valuable method for understanding complex pathophysiological conditions such as hyperthyroidism without radioactive uptake, the fate of irradiated glands or the thyroid adaptation to iodine overload. On the other hand, SIMS microscopy which combines the phenomena of secondary ion emission and mass spectrometry, makes possible the quantitative mapping of 127I on tissue section. This technique is able to characterize the functional activity of thyroid tissue without prior administration of radioiodine by measuring 127I concentration within the thyroid follicles. Furthermore, SIMS microscopy can be used to determine the extent to which exogeneous iodine affects the regulation of iodine within the thyroid follicles. Both methods were used to evaluate the quantitative changes in thyroid 127I induced by amiodarone overload. TIC measurements shows that hyperthyroidism occurred only in patients who increased their iodine stores, while the patients who developed hypothyroidism had low iodine stores. These data demonstrate that the mechanisms by which subjects who become hypothyroid under amiodarone iodine overload differ from those of subjects who remain euthyroid or become hyperthyroid: iodine organification is blocked in hypothyroid patients and increased in the euthyroid and hyperthyroid patients. The SIMS microscopy data obtained in mice demonstrated that the thyroid response to amiodarone is related to dietary iodine intake leading to an increase in iodine stores in iodine deficient mice and a decrease in iodine supplemented mice. These results could explain that hyperthyroidism with high thyroid iodine content occurred in areas with low thyroid iodine intake and hypothyroidism with low thyroid iodine content in areas with a supplemented iodine diet. PMID- 1285029 TI - Effect of a single oral dose of L-thyroxine (150 micrograms) on serum thyroid hormone and TSH concentrations in clinically euthyroid goitrous patients. AB - Serum TT4, FT4, TT3, FT3 and TSH, concentrations were measured before and 0.5, 1, 2, 3, 4, 5 hours after a single oral dose of L-T4 (150 micrograms) in 21 clinically euthyroid goitrous patients on a long-term therapy program. The mean basal TT4 concentration, 8.85 +/- 0.52 micrograms/dl (mean +/- se), increased significantly at the second hour (10.04 +/- 0.52 micrograms/dl, p < 0.001) and reached the highest value at the third hour (10.35 +/- 0.55 microgram/dl, p < 0.001). Subsequently the mean serum TT4 concentration remained elevated until the fifth hour (10.20 + 0.60 microgram/dl, p < 0.001). The mean basal value of FT4 concentration, 8.66 +/- 0.40 pg/ml, increased significantly at 30 minutes (9.19 +/- 0.40 pg/ml, p < 0.01) and reached the highest value at the third hour (11.81 +/- 0.56 pg/ml, p < 0.001). The mean basal serum FT3 concentration, 3.56 +/- 0.10 pg/ml, increased significantly 30 minutes (3.72 +/- 0.11 pg/ml p < 0.05) after L T4 administration; the mean serum FT3 concentration was significantly higher than the basal level and 1 and 2 hours as well, and reached the highest value at the third hour (3.86 +/- 0.09 pg/ml). The mean serum TT3 concentration did not show any significant change at any time. The mean basal TSH value (2.73 +/- 0.42 microUI/ml) declined progressively. At 30 minutes it decreased significantly (2.29 +/- 0.38 microUI/ml, p < 0.01) and reached the lowest value at the fifth hour (1.39 +/- 0.26 microUI/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285030 TI - Age influence on clinical features in hospitalized thyroid patients: dissimilarity between clinical and laboratory findings in adulthood. A retrospective study. AB - To evaluate the influence of age on clinical findings of thyroid disease, the records of 209 consecutive hospitalized patients with hyperthyroidism (n = 109) or hypothyroidism (n = 100) over a ten year period (1979 to 1988) were retrospectively reviewed. Patients included 51 males and 158 females, aged 21-99 years. Control euthyroid subjects (n = 70) were selected in the same age range and for similar non-thyroid illness as patients. Patients and controls were sorted by age decade of life. For each group a clinical index was calculated on the basis of 10 symptoms and 10 signs most frequently observed in thyroid disease. With increasing age, the occurrence rate of the clinical manifestations of thyroid disease decreased in patients while it increased in controls. This opposite evolution was less marked in hypothyroidism than in hyperthyroidism and was independent of biological parameters which remained stable whatever the age of patients and controls. Specific clinical features were identified for hyper- and hypothyroidism but none of them had sensitivity higher than 60% except goiter in hyperthyroid patients aged 61-80. In conclusion, a clinical diagnosis of thyroid disease is difficult in aged subjects because there are only a few specific features and their frequency is low. Therefore, in subjects over 60 years, we advocate performance of thyroid biochemical screening. PMID- 1285031 TI - Hyalinizing trabecular adenoma. AB - A case is presented of hyalinizing trabecular adenoma in a 54-year-old Japanese female. The patient underwent a hemithyroidectomy for the diagnosis of thyroid carcinoma. An intraoperative frozen section diagnosis was medullary carcinoma. Hematoxylin and eosin stained permanent sections from the surgical specimen, a well encapsulated 3.0 x 2.0 x 1 cm nodule, also led us to suspect medullary carcinoma, but immunohistochemical staining for thyrocalcitonin, CEA, and thyroglobulin showed that it was a hyalinizing trabecular adenoma. PMID- 1285032 TI - Recurrent laryngeal nerve palsy after thyroid and parathyroid surgery. Experience from Lund University. AB - All cases undergoing neck operation for thyroid or parathyroid disease at Lund University Hospital, Lund, over a 7 year period were examined with indirect laryngoscopy pre- and postoperatively for the determination of the true incidence of operatively induced palsy of the recurrent laryngeal nerves. A total of 1.048 patients were operated; 810 females and 238 males. At 439 operations, bilateral neck exploration was performed; hence, 1.487 nerves were at risk for complications. It was found that immediate postoperative recurrent laryngeal nerve palsy was induced in 72 patients (= 4.8% of nerves at risk). In 44 of these patients, the palsy was temporary and disappeared within 6 months. Therefore, a total of 28 patients developed permanent nerve palsy postoperatively. In 5 of these operations, the nerve was intentionally divided, yielding a true incidence of permanent accidental postoperative nerve palsy of 1.6% of nerves at risk. PMID- 1285033 TI - Thyroid stimulating immunoglobulins are not influenced by smoking in healthy subjects. AB - In view of the increasing suggestion of an effect of cigarette smoking on thyroid disease and in particular Graves' ophtalmophathy we investigated thyroid stimulating immunoglobulins in relation to smoking habits in healthy subjects. No difference between smokers and non-smokers could be demonstrated, therefore, our study does not support the previously suggested altered immunologic surveillance of the thyroid in cigarette smokers. PMID- 1285034 TI - Is standard 555 MBq 131I-therapy of hyperthyroidism ablative? AB - The effect of a standard 555 MBq 131I dose in ablating the thyroid gland was investigated in 116 consecutive hyperthyroid patients. Fifty-one had Graves' disease, 50 a multinodular toxic goitre and 15 had a solitary toxic nodule. 555 MBq 131I was given regardless of size or type of the gland and severity of the disease. Within one year after this dose hypothyroidism was induced in 41% of patients with Graves' disease, but in only 13% with a solitary toxic adenoma, and 6% with a multinodular gland. Forty-eight percent of the patients with a multinodular gland, 33% with Graves' disease and 13% with a solitary toxic nodule were still hyperthyroid. Since this so called ablative treatment only accomplishes hypothyroidism in 26/116 (23%) of our patients and results seem unpredictable 131I treatment adjusted according to gland size and type aiming at achieving euthyroidism could be contemplated. PMID- 1285035 TI - Inadequacy of the WHO classification of the thyroid gland. AB - In order to evaluate the reproducibility of the WHO classification of goitre, the observer variation was estimated as kappa coefficients. Three observers independently inspected and palpated the thyroid gland of 53 patients twice and assessed the thyroid according to the five grades of the WHO classification. The thyroid volume was also measured by ultrasonography. We found kappa values from 0.15 to 0.70 in the interobserver study, and from 0.02 to 0.89 in the intraobserver study. Considerable overlap between the five grades was demonstrated when the assessments were related to volume estimated by ultrasonography. Description of the thyroid gland according to the WHO classification is inaccurate and not reproducible and is therefore of limited value. PMID- 1285036 TI - Full-blown hypothyroidism associated with vitiligo and acropachy. Report of one case. AB - During the first two years after the onset of hypothyroidism, a patient with spontaneous primary myxedema developed thyroid acropachy. Fifteen years before the diagnosis of thyroid disease, he had patchy vitiligo of the face. There were high serum levels of antibodies against thyroglobulin (anti-Tg) and microsomal antigen (anti-M) were present, while the serum levels of antibodies against the second antigen of the colloid and the cell-surface antigen fell within the normal range. Moreover, antibodies to gastric parietal cells, adrenocortical cells or pancreatic islets in the serum were not present. Concerning the immuno-genetic pattern of our patient, his HLA system did not appear to confirm the well documented prevalence in whites with autoimmune disorders of an antigen specificity positive for the locus DR3. PMID- 1285037 TI - Long term therapy with a new liquid L-thyroxine preparation: bioequivalence with L-T4 tablets. AB - Seventy-four euthyroid patients with nodular goiter (55) or primary hypothyroidism (19) were selected for long term treatment with a new preparation containing L-T4 in solution (Tiroxen, Laboratori Baldacci, Pisa, Italy). Each patient underwent, before or after receiving the L-T4 in solution, long term treatment with L-T4 in tablet form at the same dose. The serum concentrations of TSH, TT4, TT3, FT4 and FT3 were measured basally and during therapy with each of the two L-T4 preparations (liquid and tablet). In the golter group, mean serum TSH concentration was 1.4 microUI/ml basally, while it was 0.47 microUI/ml following both L-T4 tablet therapy and L-T4 solution administration. Mean basal TSH value was significantly different from the two values on the therapy (p < 0.001 in each instance). Mean basal serum TT4 concentration was 8.2 +/- 0.25 microgram/dl basally while it was 9.9 +/- 0.28 microgram/dl (p < 0.001) on L-T4 tablet therapy and 9.7 +/- 0.26 (p < 0.001) on L-T4 solution administration. Mean basal serum concentration of TT3, FT4, FT3 was not significantly different from the value on the therapy, either with L-T4 tablet or with L-T4 solution. In the hypothyroid patients the high mean basal serum TSH concentration (23.6 microUI/ml) returned to normal similar values on L-T4 tablet therapy (0.96 microUI/ml; p < 0.01) and on L-T4 solution administration (1.24 microUI/ml; p < 0.01). The serum TSH concentration value during L-T4 therapy varied from unmeasurable level to 3.5 microUI/ml during the tablet administration and to 4.8 microUI/ml during the solution administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285038 TI - Relation between thyroid status and ferritin metabolism in rats. AB - Rats were made hypo and 'hyperthyroid' with propylthiouracil (PTU) and L Thyroxine (L-T) respectively. The hypo and hyperthyroid status in these rats were confirmed by serum level of T4 and T3. Liver iron was significantly increased in both the hypo and hyperthyroid animals. However, liver ferritin synthesis rate was reduced by 36% in hypothyroid rats, and elevated by 38% in hyperthyroid ones. A similar trend was seen in liver ferritin concentration. Further, serum transaminases were elevated only in animals of the hyperthyroid group. It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron. Thus, the raised serum ferritin in hyperthyroid patients may be partially attributed to increased ferritin synthesis in the liver and its possible leakage into circulation. PMID- 1285039 TI - Prevalence of thyroid abnormalities in patients with rheumatoid arthritis. AB - The prevalence of thyroid abnormalities was determined in 131 patients: group I = rheumatoid arthritis, 68 patients, group II = systemic immunological diseases (IIa Sjogren's syndrome, n = 6; IIb other rheumatic autoimmune disease, n = 17), group III = other rheumatic diseases n = 13 and control group (n = 27). Thyroid abnormalities (hypo, hyperthyroidism, nodular goiter) were frequent: 33.8% in group I, 100% in group IIa, 11.7% in group IIb. Hypothyroidism was present in 19.1% (group I), 50% (group IIa). 6% (group IIb). Autoimmune thyroiditis was found in 16.2% in group I, 100% in group IIa, 11.7% in group III. Thyroid diseases are frequent in patients with rheumatoid arthritis. Therefore thyroid tests might be performed in patients with rheumatoid arthritis. PMID- 1285040 TI - Scanning tunnelling microscopy observations of biomolecules on layered materials. AB - Scanning tunnelling microscopy (STM) has been performed on the reverse transcriptases of the human immunodeficiency virus (HIV-1) and the moloney murine leukaemia virus (MuLV). The biological molecules are adsorbed on n-type semiconducting MoTe2. The p66 (66 kD) subunit of the RT of HIV-1 is imaged by STM. Both STM and processed transmission electron microscopy (TEM) data show a spherical and horseshoe-like shape of external diameter ca. 65 A, depending on the angle of observation. The STM results show a larger diameter which is related to the curvature radius of the tip of the probing needle. The RTs of HIV-1 and MuLV exhibit a circular hole of ca. 20 A diameter in accordance with structure predictions and functioning considerations. The surface-molecule interaction is discussed in terms of the electronic properties of the semiconductor surface including the influence of small defect sites at the layered crystal surface. PMID- 1285041 TI - Location of the granulocyte-specific antigen LAN on the Fc-receptor III. AB - This report investigates the location of the binding site of a recently described granulocyte-specific alloantibody, designated LAN, which causes alloimmune neonatal neutropenia. The LAN antigen is shown to be situated on the Fc-receptor III (FcRIII). PMID- 1285042 TI - A controlled trial of intra-operative autologous transfusion in cardiothoracic surgery measuring effect on transfusion requirements and clinical outcome. AB - We carried out a prospective, controlled trial of intra-operative autologous transfusion (IOAT) in cardiac surgery using the Haemonetics Cellsaver 4, to determine the effects on transfusion requirements and early clinical outcome. Intra-operative autologous transfusion in unselected patients resulted in a reduction in the use of red cells in patients undergoing first-time operations (IOAT median 3 units, controls median 4 units, P = 0.0023), with no difference in the use of other blood products. Post-operative haemoglobin was higher in IOAT patients (IOAT 11.6 g/dl +/- 1.1 versus controls 11.2 g/dl +/- 0.98, P < 0.001). There is therefore the potential for a further reduction in homologous blood use in the IOAT group. There was no difference in early clinical outcome in the two groups; in particular the incidence of coagulopathies was not influenced by IOAT. The routine use of IOAT would add substantially to the cost of these operations. The decision to use it must therefore be based on an assessment of the value of the reduction in risk to the patient achieved by a small reduction in homologous donor exposures. PMID- 1285044 TI - [Influence of 5.7-dihydroxytryptamine on electro-acupuncture analgesia and substance P level in central nervous system of the arthralgic rats]. AB - The relation between electroacupuncture (EA) analgesia (A) and substance P (SP) level in the brain stem (BS) and lumbar spinal cord (LSC) of arthralgic rats was investigated. The rats were divided into three groups: 1)5.7-dihydroxytryptamine (5.7-DHT) + EA, 2) vehicle (V) + EA, and 3)5.7-DHT. All the animals were induced arthralgesia by injecting Freund's adjuvant 7 days after cisterna injection of 5.7-DHT or vehicle. The SP level in the BS and LSC was determined by RIA. The results indicated that in V + EA group the EA could prolong tail flick latency by 39.6%, but in other two groups did not. The SP level in LSC of V + EA group (179.1 +/- 11.5 pmol/g) was higher than that in the 5.7-DHT + EA (135.9 +/- 9.3pmol/g) and 5.7-DHT (125.8 +/- 10.0 pmol/g) groups. It suggested that both EA and arthralgia could activate the descending 5-HTergic inhibitory system to inhibit the release of SP in LSC. When the 5-HTergic system was destroyed by 5.7 DHT, the EAA was attenuated, and the SP level in LSC was lowered due to its release was decreased by EA and arthralgia. PMID- 1285043 TI - U.K. multicentre study on blood donors for surrogate markers of non-A non-B hepatitis. Part I: Alanine transferase and anti-HBc testing. AB - Blood samples from 9,215 blood donors in three U.K. centres (North London, Bristol and Manchester) were tested for their alanine aminotransferase (ALT) level and the presence of anti-HBc and anti-HCV. This paper presents the results of the ALT and anti-HBc tests. The prevalence of ALT > 45 IU/l was 3.1% overall (North London 3.06%, Bristol 4.56% and Manchester 1.97%). Manchester results were skewed by the methodology used for ALT measurement, highlighting the need for standard test methods. Anti-HBc was detected using the Wellcome enzyme immunosorbent assay (EIA) and confirmatory testing was performed using a radioimmunoassay (RIA) and the Corecell haemagglutination assay. Repeat reactive rates were 0.9, 0.79 and 0.94% for North London, Bristol and Manchester, respectively, with an overall rate of 0.9%. The confirmed positive rate was 0.73, 0.53 and 0.65% for the three centres with an overall rate of 0.63%. Donors with an ALT > 45 IU/l, or with confirmed anti-HBc, were interviewed with a medical questionnaire for risk factors. The major contributing factors in donors with a raised ALT were alcohol consumption and obesity. PMID- 1285046 TI - [Effect electroacupuncture on the neurogenic inflammation]. AB - The neurogenic inflammation caused by antidromic stimulation of the saphenous nerve was taken as an index of peripheral release of substance P. Electroacupuncture could reduce the plasma extravasation from the neurogenic inflammation by 69.7%, but electroacupuncture per se did not cause obvious plasma extravasation. In rats pretreated with capsaicin the plasma extravasation could be markedly reduced, in consistent with the reduction of substance P-like immunoreactivity in dorsal horn. It is referred that electroacupuncture might block the conveying the signals induced by nerve stimulation along the C-fibers and the axo-axonal reflex, leading to the reduction of peripheral release of substance P. Besides the mediation by different central structures, acupuncture might have direct effects on regulating peripherally the release of some inflammatory and painful mediators. PMID- 1285045 TI - [Ultrastructure identification of raphe-spinal serotonergic pain modulating system in rats]. AB - 5,6-dihydroxytryptamine was microinjected into the nucleus raphe magus (NRM) of rats. The sections of upper cervical segments were processed for immunoreactive substance P (SP). The degenerated axon terminals and immunoreactive fibers were identified by electron microscopy. The results show that the degenerated axon terminals and immunoreactive positive dendrites and axons were found in the laminae I and II of the dorsal horn. The electron-dense axon terminals were in contact with unlabelled dendrites, some also in contract with immunoreactive dendrites. In lamina II, one of degenerated axon terminals as a center was contacted by several unlabelled axonal boutons. SP labelled terminals were synapsed with unlabelled dendrites and dendritic spine; in addition, unlabelled axo-axonal synapse was found in lamina II. These results suggest that 5-HT axon terminals from NRM directly innervate SP and non-SP neurons in the laminae I and II. PMID- 1285047 TI - Principles of flap prefabrication. AB - Clinical flap prefabrication can be classified according to the basic technique of plastic surgery used for the prefabrication. There are currently three methods: (1) delay or expansion; (2) grafting; and (3) vascular induction by staged transfer. Illustrative cases are given to point out the advantages and indications for each method. A fourth, still experimental, method is based on cell biology advances that are looming on the horizon and may have revolutionary future clinical applications. PMID- 1285048 TI - Thrombosis and antithrombotic therapy in microvascular surgery. AB - Thrombosis in microsurgery can either totally or partially reduce the perfusion to the free tissue transfer. Total occlusion normally occurs at or near the microvascular anastomosis, while microscopic vasospasm in the distal microcirculation can account for malperfusion and wound healing problems. The mechanisms of the anastomotic and microcirculatory responses to thrombosis are discussed. Drug therapy for each risk zone is identified, and a rationale for therapy is given. PMID- 1285049 TI - Signaling between the extracellular matrix and the cytoskeleton: tyrosine phosphorylation and focal adhesion assembly. PMID- 1285050 TI - Role of alpha V integrins and vitronectin in human melanoma cell growth. PMID- 1285051 TI - Glycosylation-dependent cell adhesion molecule 1: a novel mucin-like adhesion ligand for L-selectin. PMID- 1285052 TI - Quantitative determination of selectin-carbohydrate interactions. PMID- 1285053 TI - Mediation and inhibition of cell adhesion by morphoregulatory molecules. PMID- 1285054 TI - Cadherins and the morphogenesis of epithelial tissues in Xenopus embryos. PMID- 1285055 TI - The effect of enalapril on cardiac arrhythmias in patients with congestive heart failure. AB - The purpose of the study was to evaluate the effect of enalapril on the frequency of ventricular premature beats in patients with congestive heart failure. The study group consisted of 30 patients with a mean age of 47 +/- 0.6 years with chronic congestive heart failure (NYHA classes III and IV) due to primary dilated cardiomyopathy and cardiomyopathy in the course of ischaemic heart disease. Initial therapy with digitalis and diuretics was supplemented with enalapril at a dose of 5-20 mg daily. Initially and at three months after enalapril, the following parameters were evaluated: NYHA functional class, the presence of premature ventricular beats in 24-hour ECG recording and left ventricular function by echocardiography. The scheduled therapy was completed by 23 patients; in 5 patients, the intake was discontinued because of hypotension, one patient died after 14 days due to worsening heart failure, and one patient was submitted for pacemaker implantation. Clinical improvement manifesting itself by a shift to lower NYHA classes was found in 20 patients. A reduced number of premature ventricular beats was observed in 52% of the patients. Termination of cardiac arrhythmias, especially of complex beats, was parallel to the circulatory improvement. PMID- 1285056 TI - Anti-hypertensive treatment with magnesium-aspartate-dichloride and its influence on peripheral serotonin metabolism in man: a subacute study. AB - Dichlormagnesium-aspartate-hydrochloride was given to 12 patients with mild hypertension in antihypertensive indication at a dose of 10.5 mmol Mg2+/day for 3 months. Blood pressure normalized (from 161.7 +/- 3.4/95.8 +/- 0.8 mmHg to 140.4 +/- 4.0/81.7 +/- 0.9 mmHg, after the third month (p < 0.01). While no changes in Mg2+ concentration in serum were observed in patients with normomagnesaemia, in hypomagnesaemic patients vS-Mg level normalized. Renal excretion of Mg2+ increased: from 3.41 +/- 0.36 before to 5.7 +/- 0.57 mmol Mg2+/24 h after treatment, p < 0.01. Mean plasma serotonin (5HT) concentration showed no changes, although a trend towards an increase in platelet 5HT content was observed. Elevated pre-treatment plasma 5-hydroxyindole acetic acid (5HIAA) concentrations normalized (from 137.29 +/- 20.3 to 78.96 +/- 31.64 nmol/l after the third month, p < 0.05). These findings point to a platelet-stabilizing effect of Mg2+. Fractional excretion of 5HIAA increased (from 1.42 +/- 0.27 to 5.4 +/- 1.22 after treatment, p < 0.01) while mean urinary 5HIAA excretion remained unchanged. It is deduced that a) total body 5HT and 5HIAA production was not affected; b) a long term supplementation of Mg2+ stimulates the transport of 5HIAA in proximal tubules and, probably, intrarenal 5HIAA synthesis. A functional block in 5HT metabolism under Mg2+ treatment is anticipated. Thus, Mg2+ supplementation has renal and extrarenal effects that are important in treating hypertension and its complications. PMID- 1285057 TI - [An experimental study model of human neo-angiogenesis. Heterotopic graft of the cornea in nude mice]. AB - Two grafting methods were devised to transplant heterotopically human corneas to nude mice. Half of them were secured on the mesenterium, enclosed in a small intestine ring; the others were stitched to the anterior abdominal muscles after removal of a muscular disc. We used theses procedures to implant 13 human corneas: 7 according to the first technique and 6 tho the second one. Most of the corneas observed from Day 3 to Day 90 remained transparent along the whole grafting period. The grafts were surgically removed from Day 3 to Day 90 and submitted to an histological examination. It was not observed any morphological changes, versus normal human cornea and especially none neovascularization. These observations are fully in agreement with the persistent transparency of the corneas. With this model, many experimental studies in vivo on human corneas can be planed and conducted without any ethical restriction. PMID- 1285058 TI - [A new method for transurethral prostatic commissurotomy]. AB - Based on the principles of Shafik's prostatic commissurotomy, we have developed a new transurethral prostatic commissurotomy, which is characterized by cutting, layer by layer and section by section, the urethral mucosa, the bladder muscle layer and the prostate tissue within combined part of the urethra and prostate and by cutting the prostatic capsule with electrocoagulation. The comparison of clinical objective indexes has proved that the method is applicable to high risk patients with prostate hyperplasia and neck contracture leading to urethral obstruction after TURP. PMID- 1285059 TI - Expression of ABO blood-group antigenic determinants identified by monoclonal antibodies B7H4 and D1E8 in normal human tissues and organs. AB - Human blood group antigens are genetically determined structures of undefined nature found not only in red blood cells but also in various tissues. Monoclonal antibodies against A and B human blood group antigens (B7H4 and D1E8) were obtained. Their tissue compatibility was tested in 11 different normal human organs taken from people with A1 and B blood group phenotypes. The antigen antibody reaction was visualized using the indirect immunoperoxidase technique. The results of the study showed that the antibodies B7H4 and D1E8 react specifically with the tissue blood group antigens in healthy subjects. The findings obtained in most of the tested organs were in accord with those described by other researchers. Differences were found only in the stomach, urothelium, the lungs and the thyroid gland. A possible explanation of the results is the difference in the epitopes recognized by the monoclonal antibodies used by us and the blood group antibodies applied by other researchers. It is suggested that the monoclonal antibodies against the human blood group antigens A and B obtained by us could be used to establish suspected modification of ABH antigens in the process of oncogenesis. PMID- 1285060 TI - Autoreactive T cells in multiple sclerosis. PMID- 1285061 TI - Antigen-specific tolerance as a therapy for experimental autoimmune encephalomyelitis. AB - The effects of neuroantigen-specific tolerance on the induction and effector stages of EAE were examined. Tolerance induced by the i.v. injection of syngeneic splenocytes coupled with purified neuroantigens or encephalitogenic peptides of MBP and PLP using ethylene carbodiimide was extremely effective in both prevention and treatment of acute and relapsing forms of EAE in Lewis rats and SJL/J mice. The unresponsiveness is rapidly-induced, dose-dependent, long lasting, efficient, MHC class II-restricted, and exquisitely antigen-specific. This procedure targets only effector cells bearing clonotypic receptors specific for the autoantigen/autoepitope and thus does not depend upon the autoimmune response being dominated by a restricted T cell repertoire. Moreover, it does not require that the response to the autoantigen be dominated by recognition of a specific epitope(s) within a particular autoantigen, or even the identification of the specific autoantigen. The results also demonstrate the usefulness of peripheral tolerance induced by antigen-coupled syngeneic splenocytes for identifying the fine specificity of autoimmune T cell responses which appear to change during the progression of relapsing EAE. Thus, this technique offers major advantages over many other currently employed immunoregulatory strategies and is therefore relevant for establishment of therapeutic protocols for the antigen specific treatment of human T cell-dependent autoimmune disorders. PMID- 1285062 TI - EAE: a model for immune intervention with synthetic peptides. AB - The cellular and molecular requirements for the autoimmune disease EAE are being defined in increasing detail through intense scrutiny of critical autoantigenic peptides, class II MHC molecules, and alpha beta TCRs involved in the disease process. This study has led to novel immunotherapeutic approaches, many of which are based on the administration of synthetic peptides. Since short peptides are understood to be the minimal antigenic units bound by MHC molecules for recognition by T cells, they are attractive experimental tools for finely modulating specific immune responses. It is clear that a large number of defined peptides can dramatically influence the course of EAE. Table IV lists a number of potential mechanisms which may mediate disease prevention. Increasing evidence supports the idea that prevention of autoimmune disease can result from MHC blockade by peptides which competitively bind to class II molecules. However, for some peptides such as the perplexing partial agonist Ac1-11[4A], the mechanism by which these precisely defined units act is not yet fully understood. Numerous hurdles hinder immediate clinical application of peptide-based immunotherapy. Nevertheless, the knowledge gained by probing experimental autoimmunity with defined peptides promises to inspire original and practical approaches to treating human autoimmune disease. PMID- 1285063 TI - Myelin specific, autoaggressive T cell clones in the normal immune repertoire: their nature and their regulation. PMID- 1285064 TI - Comparison of Hoechst 33342 and propidium iodide as fluorescent markers for sperm fusion with hamster oocytes. AB - Hamster oocytes were loaded with the DNA dyes Hoechst 33342 or propidium iodide. Oocytes incubated in 10 mumol Hoechst 333421(-1) showed intracellular fluorescence within 10-20 s of exposure, as did hamster and guinea-pig spermatozoa. Impaled oocytes to which acrosome-intact hamster spermatozoa were bound before injection of Hoechst 33342 showed dye transfer to adhering spermatozoa within 2 min of injection. Oocytes loaded passively with Hoechst 33342 showed dye transfer to bound, acrosome-intact hamster spermatozoa within 10 min. On ultra-structural examination, no bound, acrosome-intact hamster spermatozoa (n = 311) were found to be fused. By contrast, oocytes incubated with 10 mumol propidium iodide l-1 showed no intracellular fluorescence after 2 h, although in approximately 50% of oocytes, fluorescence developed rapidly in the first polar body. Oocytes injected with propidium iodide showed intracellular fluorescence but no dye transfer to bound, acrosome-intact hamster spermatozoa. Oocytes impaled on pipettes containing propidium iodide showed no dye transfer to unlabelled oocytes with which they were brought into contact, whereas in similar experiments using Hoechst 33342 detectable dye transfer to an adjacent oocyte occurred within 10 min. Oocytes loaded with propidium iodide transferred propidium iodide to fusion-competent guinea-pig spermatozoa during in vitro fertilization. Normally, between 20 and 40 spermatozoa bound per oocyte, and the percentage of spermatozoa showing dye transfer varied between 0 and 41%. Dye transfer occurred within 5-45 min. Only those nuclei that showed propidium iodide transfer subsequently decondensed, suggesting that dye transfer is correlated with fusion. The presence of fused spermatozoa was confirmed by ultrastructural examination of oocytes. In separate experiments, hamster and guinea-pig spermatozoa showed detectable fluorescence from propidium iodide within 20 s of osmotic rupture or membrane stripping by detergent, suggesting the lag in dye transfer to sperm nuclei during fertilization reflects a delay in sperm-oocyte fusion following adhesion. This evidence suggests that Hoechst 33342 could be an unreliable marker for sperm-oocyte fusion in fertilization because of its capacity for passive movement from oocyte to spermatozoon. This problem can be overcome using oocytes injected with propidium iodide. With this technique, it was possible to show that fusion-competent guinea-pig spermatozoa that are held in pipettes will fuse with hamster oocytes when placed mechanically against the oocyte surface. PMID- 1285065 TI - Characterization of equine zona pellucida glycoproteins by polyacrylamide gel electrophoresis and immunological techniques. AB - This study was designed to explore the composition of the equine zona pellucida (EZP) by one- and two-dimensional polyacrylamide gel electrophoresis (1D- and 2D PAGE), silver staining and immunoblotting techniques. Antral follicles palpable on frozen-thawed equine ovaries were aspirated with a needle and syringe, and the resultant follicular fluid, cellular material and oocytes were pooled. Oocytes were placed in Petri dishes, moved by narrow-bore pipette to droplets of phosphate-buffered saline (PBS) and mechanically cleaned of cumulus cells. The EZP from these collected oocytes was solubilized, and then analysed by 1D- and 2D PAGE. Silver stained 2D-PAGE of the EZP revealed the presence of three EZP glycoprotein families of apparent molecular mass ranges of 93-120 kDa, 73-90 kDa and 45-80 kDa. Immunoblot analysis of EZP glycoproteins resolved by 2D-PAGE using rabbit antisera against pig zonae pellucidae (R alpha HSPZ) confirmed the presence of three EZP glycoprotein families and established the existence of common epitopes between equine and porcine ZP glycoproteins. Further immunodetection using 2D-PAGE-separated glycoproteins illustrated that the 45-80 kDa family is recognized by the monoclonal antibody R5, developed against the porcine ZP glycoprotein of molecular mass 55-120 kDa. Guinea-pig antiserum against endo-beta-galactosidase-treated rabbit ZP 55 kDa glycoprotein (R55K), which specifically recognizes the rabbit ZP glycoprotein with the lowest molecular mass, also recognized the EZP 45-80 kDa glycoprotein family. Guinea-pig polyclonal antisera developed against total heat-solubilized rabbit ZP (GP alpha HSRZ) recognized the 73-90 kDa EZP glycoprotein family exclusively. After heat solubilization and treatment of EZP with endo-beta-galactosidase to remove polylactosaminoglycans, silver stained 1D-PAGE again demonstrated the presence of three glycoproteins with apparent molecular masses of 60, 75 and 90 kDa. The partially deglycosylated 60 kDa equine glycoprotein is recognized on immunoblot by the monoclonal antibody R5; the 75 kDa EZP glycoprotein is recognized by GP alpha HSRZ; and all three EZP glycoproteins separated by 1D-PAGE are recognized by R alpha HSPZ. These data add further support to the concept of cross-species zona pellucida glycoprotein antigenicity. PMID- 1285066 TI - [Anaphylactic shock due to modified fluid gels: 2 case reports]. AB - Colloid solutions can give severe anaphylactic accidents. We are reporting two cases from our department. FIRST CASE: a sixty eight years old man perfused with Plasmion solution (Gelatin plasma substitute) before spinal anesthesia, presented sudden hypotension and diffuse skin rush. Second case: a twelve years old girl, receiving a Plasmion solution to correct a hypovolemic shock in I.C.U, presented a severe bronchospasm and a worsening of the hypotension. These accidents are explained by immunologic reactions or by direct histamine release. Their incidence is between 0.01 and 0.8 percent depending on the used solution. They are prevented by an antihistaminic premedication for the gelatin plasma substitutes and by an haptenic inhibition for Dextran (polysaccharide plasma substitutes). The new colloid solutions, based on hydroxyethylstarch, seems to give much less allergic reactions. PMID- 1285067 TI - Immunohistochemical determination of complement activation in joint tissues of patients with rheumatoid arthritis and osteoarthritis using neoantigen-specific monoclonal antibodies. AB - Murine monoclonal antibodies specific for neoepitopes expressed by C9 incorporated into membrane attack complexes and by membrane-bound C3b and iC3b have been prepared and characterised. These reagents were used to determine the extent and locus of complement activation in synovial-tissues obtained from patients with rheumatoid arthritis and osteoarthritis. In the four rheumatoid arthritis patients there was extensive deposition of C3 activation products and C5b-9 complexes onto the synovial membrane and the pattern of deposition of both neoantigens in serial tissue sections was very similar. There was less extensive staining for C3 and, particularly, C9 neoepitopes on the apical surface of vessel endothelia. In two of four osteoarthritic patients a similar pattern of C3 and C9 neoepitope deposition was found; in the remaining patients no C5b-9 could be located. Synovial vessel walls, but not synovial cells, from both groups of patients stained extensively for the complement regulatory protein CD59. In synovial membranes from patients with osteoarthritis, C9 appeared to be present predominantly in SC5b-9 complexes whereas in rheumatoid arthritis patients no evidence of S-protein incorporation into membrane attack complexes could be demonstrated, suggesting that in rheumatoid arthritis there is damage to the synovial membrane as a result of complement activation and C5b-9 deposition. PMID- 1285068 TI - Various responses of lymphocytes to Epstein-Barr virus in patients with common variable immunodeficiency. AB - The responses of lymphocytes to Epstein-Barr virus (EBV) were investigated in five patients with common variable immunodeficiency (CVID). In three patients with CVID in whom the percentages of CD20+ cells and CD21/EBV receptor+ cells were markedly reduced, PBMCs and/or B cells did not respond (or scarcely) to EBV. This may be due to reduction of B cell numbers or reduction of EBV receptor bearing cells. In one patient with CVID in whom the percentages of CD20+ cells and CD21/EBV receptor+ cells were mildly reduced, PBMCs and/or B cells responded well to EBV and secreted immunoglobulin (Ig). This result shows that the patient's B cells with EBV receptors are sufficient to transduct EBV-signals into the nucleus and to respond to EBV. In another patient in whom the percentages of CD20+ cells and CD21/EBV receptor+ cells were not reduced, PBMCs mildly responded to EBV and scarcely secreted Ig. This result shows that the patient's B cells with EBV receptors may not be sufficient to transduct EBV-signals into the nucleus and to respond to EBV. PMID- 1285069 TI - Protooncogenes in the regulation of normal hematopoiesis. An antisense approach. PMID- 1285071 TI - Myelin-deficient mutant mice. An in vivo model for inhibition of gene expression by natural antisense RNA. PMID- 1285070 TI - Therapeutic applications of antisense DNA in the treatment of human leukemia. PMID- 1285072 TI - Gene inhibition of HIV-1 replication. A comparative and mechanistic study. PMID- 1285073 TI - Design, synthesis and assay of tetrapeptide-acridine mimics of ribonuclease. PMID- 1285074 TI - In vitro effect of levamisole on the neutrophil activity in rainbow trout (Oncorhynchus mykiss). AB - An in vitro immunization and cultivation method for fish spleen organ section was used to investigate the effects of levamisole on the neutrophil activity. After 10 days of culture with either 50 micrograms/ml, 25 micrograms/ml, 5 micrograms/ml or no levamisole in the media, the nonspecific defense reactions were measured by determining the metabolic activity of neutrophils by using the nitroblue tetrazolium test, and phagocytic and adherence indexes by incubating the fish cells with suspensions of formalin-killed Staphylococcus aureus. Elevations were found in nonspecific cellular defense in the 5 micrograms/ml levels of levamisole. The 25 micrograms/ml levels instigated a slight elevation in nonspecific cellular defense and the 50 micrograms/ml levels suppressed all indicators, whether levamisole was given alone or combined with Yersinia ruckeri O-antigen or DNP-Ficoll. These antigens are themselves nonspecific cellular defense stimulators, and a synergistic effect was evident when combined with 25 micrograms/ml and 5 micrograms/ml levels of levamisole. PMID- 1285075 TI - Advisory Committee on Medical Training. Report and Recommendations on Undergraduate Medical Education. PMID- 1285076 TI - [Physicians and health promotion in Italy: the initial results of a sampling study]. PMID- 1285077 TI - Alcohol, smoking and body mass index in a sample of adults from the general population. PMID- 1285078 TI - [The prevention of traveler's malaria: current findings]. PMID- 1285079 TI - [The bacteriological and virological characteristics of the sea and estuarine waters along the Tyrrhenian coast]. PMID- 1285080 TI - [Medical-veterinary collaboration in the field of zoonoses]. PMID- 1285081 TI - [The microbiological profiles of rabbits, pigeons and game in the province of Ferrara]. PMID- 1285082 TI - Similar distribution of insulin-like growth factor binding proteins-1, -2, -3 in human fetal tissues. AB - The actions of insulin-like growth factors (IGFs) are modulated by several specific binding proteins (IGF BPs). Since the anatomical distribution of IGF BPs is likely to dictate IGF bioavailability we used immunocytochemistry to localize IGF BP-1, -2, and -3 in early second trimester human fetal tissues. Primary antisera were directed against hIGF BP-1, bIGF BP-2 and hIGF BP-3 respectively, and showed less than 5% cross-reaction with heterologous IGF BP species. The distribution of immunopositive staining was similar for each IGF BP in many tissues being prominent in the epithelial lining of the gut, kidney and lung; in epidermis, adrenal cortex and pancreatic endocrine tissue; and in association with membranes of skeletal muscle fibres and cardiocytes. Unlike IGF BP-1 -2, IGF BP-3 was barely detectable in liver and absent from epiphyseal chondrocytes. Conversely, IGF BP-3 alone was visualized within neurons of the cerebral cortex. The co-distribution of IGF BPs in many human fetal tissues suggests that they may co-ordinately regulate IGF bioavailability in target tissues and modify IGF: receptor interactions. PMID- 1285083 TI - Membrane perforation by Entamoeba histolytica: structural implications derived from the sequence of the pore-forming peptide. AB - The pore-forming peptide amebapore is considered crucial for the cytolytic activity of E. histolytica. Isolation and subsequent molecular cloning of the peptide allowed predictions as to its secondary structure, most of which were confirmed by experimental data. Here, a computer-aided approach is applied to identify, within the peptide, highly amphipathic helical segments predicted to interact with biological membranes. Two putative alpha-helices fulfill the criteria of membrane-seeking domains and in this respect resemble small lytic peptides of various origins. PMID- 1285085 TI - Sequence and structure of the galactose adherence lectin of Entamoeba histolytica. PMID- 1285084 TI - Cloning and partial characterization of an antigen detected on membrane surfaces of non-pathogenic strains of Entamoeba histolytica. AB - A novel and unique mAb (318-28) which specifically interacts with a 60 kDa antigen that is found only on the surfaces of non-pathogenic (NP) strains of E. histolytica has been recently characterized. The antigen appears to be present also on (NP) cyst forms of amebas but was not detected on any of the various (P) strains tested. It was also not found on other Entamoeba species such as Moshkovskii, Laredo, Huff, Coli, Gingivalis, or Invadens. Clinical trails for the differentiation of (P) and (NP) amebas directly from stools using this mAb are in progress. Cloning of the gene encoding for the (NP)-specific antigen was achieved after screening with mAb 318-28 a lambda gt11 expression library of NP strain SAW 1734R. No sequence homology to any known protein was found in data bases. PMID- 1285086 TI - A rapid colorimetric assay with the tetrazolium salt MTT and phenazine methosulfate (PMS) for viability of Entamoeba histolytica. AB - A rapid colorimetric assay for viability of E. histolytica trophozoites using the tetrazolium salt MTT and phenazine methosulfate (PMS) was developed. The MTT is normally reduced by dehydrogenases of viable cells and transformed to formazan, a colored compound; the reaction is catalyzed by PMS. Trophozoites of E. histolytica were incubated in the presence of MTT and PMS during 15, 30, 45, 60 and 75 min, at 37 degrees C. Trophozoites killed by heat or cold were used as controls. The formazan produced into the cells was extracted with isopropanol-HCl and the optical density (OD) was measured at 570 nm. There was a linear relation between the number of viable trophozoites and the OD570 (r2 = 0.98). The trophozoites killed by cold or heat did not reduce MTT. The optimal time of incubation with MTT/PMS was 45 min. The MTT/PMS assay for determining viability of E. histolytica trophozoites is reproducible, rapid and easy to perform and it could be useful to study cytotoxicity and susceptibility to drugs. PMID- 1285087 TI - Structural organization of chromatin during the cell cycle of Entamoeba histolytica trophozoites. AB - The nuclear division of E. histolytica trophozoites was analyzed by using specific stains for DNA, with the aim to define the sequential changes of chromatin during its life cycle. Furthermore, we characterized the internal structural arrangements of microtubules in the microtubular organizing center (MTOC) and determined the number of chromosomes and its association with the spindle. The MTOC is formed by multiple microtubule-nucleating centers, that are involved in the displacement of DNA during nuclear division. We found the existence of a single MTOC in one pole of the nucleus at early anaphase. Our results lead us to propose a new hypothesis in which it is suggested that metaphase corresponds to the arrangement of condensed DNA bodies, or "chromosomes" around the MTOC and, through the assembly of microtubules, one set of uncondensed chromatin is displaced to the opposite pole of the nucleus, while the other remains condensed and associated to the original MTOC. We observed six chromosomes in our preparations, corroborating previous observations (2,3). Whether or not a new MTOC is formed during nuclear division remains to be clarified. PMID- 1285088 TI - Modulation of acetylcholine receptor channel by a polar component isolated from toxic Ostreopsis lenticularis extracts. AB - Methanol extracts obtained from O. lenticularis clones are toxic to mice and inhibit acetylcholine-induced contractions in frog skeletal muscle. Chromatographic fractionation of extracts produced two major fractions with different retention times. Single channel recordings in myocyte membrane patches exposed to more polar fraction showed the appearance of acetylcholine-activated channels whose mean current amplitude was nearly half that of the controls. Channel open times under control and experimental conditions were similar. Thus, this dinoflagellate fraction reduces the ionic conductance of nicotinic receptor channels without altering their lifetime. PMID- 1285089 TI - Advanced techniques: developing quality drawings. AB - Just like writing, developing ideas for illustrating your articles is a skill you can learn. With creativity, planning, and a cooperative relationship with a graphic artist you can include drawings that enhance your reader's appreciation of every publication you write. PMID- 1285090 TI - A survey of invasive Haemophilus influenzae infections. AB - A survey of invasive H. influenzae infections has been underway in six regions of England and Wales since September 1990. In the first year, there were 433 cases of which 362 (84%) were due to H. influenzae type b (Hib). The majority of Hib infections were in children aged less than 5 years; there being an annual incidence of 26.4/100,000 in this age group. Meningitis occurred in 56% of cases of Hib infection. The results confirm previous evidence of the need to incorporate Hib vaccination into the childhood immunisation schedule. The ongoing survey data will provide useful information to assess the impact of an Hib immunisation programme. PMID- 1285091 TI - An outbreak of hepatitis A. PMID- 1285092 TI - Hospital-acquired cryptosporidiosis. PMID- 1285093 TI - Raw eggs and body builders. PMID- 1285094 TI - Voluntary testing to measure HIV prevalence in sexually transmitted disease clinics. AB - Voluntary HIV testing was used to study the extent of HIV-1 infection in patients attending sexually transmitted disease (STD) clinics in England and Wales between 1985 and 1990. Homosexual and bisexual men and 10-20% of heterosexual men and women were invited to complete a study record and have an HIV-1 antibody test. The rate of newly diagnosed HIV-1 infection was higher in homosexual and bisexual men than in heterosexual clinic attenders. It was also higher in patients attending clinics in the South East compared with those attending clinics in other regions. From 1988 onwards, HIV infection was identified in heterosexual men and women who did not report behavioural risk factors associated with increased risk of HIV transmission. In the early years of the study, the proportion that agreed to complete a study record and have an HIV-1 antibody test was high in all groups. This proportion declined in those attending clinics in the South East, particularly among heterosexual men and women, less than 50% of whom agreed to take part in the study in 1989 and 1990. The decline in acceptance rate made voluntary testing unsuitable for monitoring trends in HIV infection. Unlinked anonymous HIV testing, which minimises the effect of participation bias, has become the method of choice for monitoring the prevalence of HIV infection. PMID- 1285095 TI - Methicillin-resistant Staphylococcus aureus in England and Wales. AB - Methicillin-resistant Staphylococcus aureus (MRSA) were detected soon after the introduction of methicillin in 1960, and reports of their isolation increased up to 1971. Changes in antibiotic usage were associated with a fall and then, in the early 1980s, a further rise in the number of reports. This article reviews the various surveys that have been conducted to establish the frequency, distribution and strain varieties of MRSA. The first strain to be recognised as epidemic (ie, affecting more than one hospital), was defined by phage typing and antibiogram, confirmed with molecular typing, and designated EMRSA-1. It was first detected in 1981 and became progressively more widespread until it began to decline in 1987. Only three health regions reported this strain in the first quarter of 1991. EMRSA-2 has remained restricted to the South East and South West Thames regions. EMRSA-3 appeared in the South East Thames region in 1987 and has since spread, being reported from eight health regions in the first quarter of 1991. At least 11 other strains of MRSA affecting more than one hospital have been detected and ten endemic strains (restricted to single hospitals) have been identified. Imported strains of MRSA, often introduced following the repatriation of road traffic accident victims, may include strains with epidemic potential and local spread has followed importation in at least two incidents. Continued surveillance of epidemic MRSA strains and the search for simple and widely applicable markers, such as unusual antibiotic resistance patterns or biochemical features, are needed for the prompt application of control measures. PMID- 1285096 TI - Hazardous incidents and immunity to hepatitis B. AB - In the period March 1989 to October 1990, Leeds Public Health Laboratory received reports of 2975 needlestick and similar incidents involving National Health Service staff where there was a risk of transmission of hepatitis B virus. Despite an active immunisation programme in the hospitals where staff worked, 50% of those involved showed no evidence of immunity. In reviewing their immunisation programmes, health authorities should take account of those groups of staff who are at risk of exposure and ensure that all those included in the programme are encouraged to take up the offer of immunisation. PMID- 1285097 TI - The epidemiology of pertussis in the Republic of Ireland. AB - Epidemiological data on pertussis in the Republic of Ireland have been gathered annually since 1941. However, no detailed analysis of these data has, until now, been carried out. Fifteen epidemics occurred between 1941 and 1989, an average of one per 3.1 years, which is similar to epidemic intervals observed elsewhere. After the introduction of a vaccine in the 1950s, annual pertussis notifications declined, from 175 per 100,000 in 1956 to 7.6 per 100,000 in 1972. Following adverse publicity in 1973, uptake of the vaccine fell to 30% in 1976. Although uptake has increased again in recent years, it has levelled out at only 40-45% and large epidemics of pertussis occurred in 1985 and 1989. At the same time, mortality from pertussis has fallen to almost negligible levels. Most cases occur in children more than one year of age. Changes in the vaccination schedule could have a major impact on the incidence of the disease in the Republic of Ireland. However, if a further decline in the incidence of the disease is to be achieved, parents have to be persuaded of the benefits of pertussis vaccination. PMID- 1285098 TI - Communicable disease in New Zealand. AB - Communicable diseases remain a major problem in New Zealand; one which often only comes to the attention of management when an outbreak occurs and health care dollars are required for disease control. Hepatitis B and rheumatic fever remain the two diseases that place New Zealand in the developing nation league. Overall, the impact on mortality is low (only 5% in the 1-14 year age group) as is the impact on potential years of life lost. Morbidity figures are not known with any degree of accuracy as they are dependent on a notification system acknowledged to be deficient and hospital discharge data which include only a fraction of cases for a few serious diseases. The main preventive action hinges on the childhood immunisation programme which has undergone recent change. The true impact of environmental hygiene measures, health promotion and education has not been evaluated. PMID- 1285099 TI - Antibiotic-resistant pneumococci in the United Kingdom. AB - Pneumococcal pneumonia and meningitis remain common infections with significant morbidity and mortality. For many years, penicillins or cephalosporins, erythromycin and chloramphenicol have been the mainstay of chemotherapy for these and other pneumococcal infections. Resistance to these antimicrobial agents has increased worldwide and resistant pneumococci are now isolated with increasing frequency in the United Kingdom. This article reviews the results of antimicrobial susceptibility and serotyping studies carried out over the last five years on UK isolates of Streptococcus pneumoniae referred to the Streptococcus and Antibiotic Reference Laboratories of the Division of Hospital Infection for serotyping or confirmation of antibiotic resistance. During this period there has been a marked increase in the referral of pneumococcal isolates resistant to one or more of the antimicrobials commonly used for treatment. The implications for antimicrobial therapy and vaccination policy are discussed. PMID- 1285100 TI - Hepatitis A and travel abroad: a study of notifications in Birmingham. AB - One hundred and seventy-two cases of viral hepatitis A (or 'infective hepatitis' or 'infective jaundice' judged to be viral hepatitis A) were notified in Birmingham in the 15 months from January 1990 to March 1991. Forty patients had travelled abroad in the three months prior to onset, 30 of whom had been to the Indian subcontinent. A survey of general practitioners attending to patients going abroad indicated that human normal immunoglobulin (HNIG) was rarely given to intending travellers, whereas other recommended immunisations often were. Furthermore, a sizeable proportion of travellers did not attend their general practitioners prior to departure. Interventions aimed at encouraging attendance, and the administration of HNIG prior to travel to endemic areas, could reduce the incidence of hepatitis A substantially, particularly in areas with a large population of Asian origin. PMID- 1285101 TI - Giardiasis--a cause of travellers' diarrhoea. AB - A surveillance programme using postal questionnaires was set up to monitor giardiasis in Bristol. Ninety-seven questionnaires were returned from 117 index cases in the first year. Cases appeared to fall into one of three main groups, namely, pre-school children (23 cases), those who travel abroad (22 cases had travelled in the month prior to the onset of their symptoms), and those who engaged in recreational water use prior to the onset of their illness (44 out of 66 cases aged 10 years or more). Routine surveillance data can indicate important routes of transmission of giardiasis in the local community. PMID- 1285102 TI - 'COVER' (cover of vaccination evaluated rapidly): 21. PMID- 1285103 TI - Heterosexually acquired HIV-1 infection: cases reported in England, Wales and Northern Ireland, 1985 to 1991. AB - By the end of 1991, there had been 417 reports of AIDS and 1620 reports of HIV-1 infection in persons in England, Wales and Northern Ireland who probably acquired their infection through sexual intercourse between men and women. Between 1986 and 1991, the proportion of AIDS cases attributable to heterosexual transmission increased from 2% to 14% and of diagnosed HIV-1 infections from 4% to 23%. Reported HIV-1 infections inadequately reflect the extent of infection as only individuals choosing to be tested can be reported. HIV-1 infection acquired during heterosexual intercourse may be the result of transmission from partners who were infected by routes other than heterosexual transmission (first generation transmission) or of transmission from infected partners who were themselves infected through heterosexual intercourse (second generation transmission). Of the 417 cases in which AIDS was acquired through heterosexual intercourse, 42 (10%) were categorised as due to first generation transmission, 328 (79%) as second generation transmission--abroad, and 47 (11%) as second generation transmission--UK. Transmission categories could be allocated to 1438 of the 1620 reports of HIV infection: 17% were categorised as first generation, 74% as second generation--abroad, and 9% as second generation--UK. Heterosexual transmission of HIV infection is increasing, both in individuals acquiring their infection abroad as well as those who become infected in the United Kingdom. PMID- 1285105 TI - Vaccine efficacy in a measles immunisation programme. AB - During a measles outbreak in Northern Ireland (between October 1988 and March 1989) it was noted that a proportion of cases had occurred in children who had previously been vaccinated against measles. A study was, therefore, set up to provide a rapid estimate of vaccine efficacy. Vaccine efficacy was calculated to be 94% (95% confidence limits, 91% to 96%). Investigation of the computerised records at 31 December 1991 revealed that 94% of children in the study cohort had received measles vaccine. As vaccination coverage increases, a higher proportion of cases of measles will, inevitably, have a history of vaccination. PMID- 1285104 TI - Second generation heterosexual transmission of HIV-1 infection. AB - Reports of 217 HIV-1 infected persons have been investigated. Initially, 122 were described as having no identified risk of HIV infection and 95 were described as probably infected through heterosexual intercourse. The sexual partners of 34 of these 95 cases were reported as having acquired their infection heterosexually in the UK but information on the risk status of the sexual partners of the remaining 61 cases was lacking. Telephone follow-up through microbiologists and clinicians resulted in the recategorisation of 132 cases. Interviews were conducted with 22 HIV infected heterosexuals without a major risk for HIV infection, either in themselves or their sexual partners, and who had no evidence of heterosexual exposure outside the UK. Interviews confirmed the categorisation of 15 cases (9 male, 6 female) as due to second generation HIV-1 infection ie, infection acquired through heterosexual intercourse in the UK with a partner who also became infected through heterosexual intercourse. A possible chain of transmission is described involving three of these 15 cases. PMID- 1285106 TI - Meningococcal infections in England and Wales: 1991. AB - There were fewer reports of cases of meningococcal infection in England and Wales during 1991 than in 1990. The number of isolates received at the Meningococcal Reference Laboratory decreased by 102 (7%), largely due to fewer strains being received from South West Thames, North East Thames and North Western regions. Group C infections showed a greater decrease than group B, with 16% fewer strains reported in 1991 than in 1990. Eight per cent of the strains received during 1991 showed reduced susceptibility to penicillin (MIC > 0.16mg/l). PMID- 1285107 TI - A survey of emergency penicillin treatment for meningitis. AB - The case fatality rate for meningococcal meningitis has changed little in recent years. A study of persons admitted to hospital in Bristol with suspected meningitis found that only five of the 41 cases admitted in 1991 were given penicillin prior to admission. Possible reasons for this include lack of awareness of the need, reluctance to give injections to children, uncertainty about dosage, failure to carry injectable penicillin and diagnostic uncertainty. PMID- 1285108 TI - Control of meningococcal disease. PMID- 1285109 TI - A pseudo-outbreak of cryptosporidiosis. PMID- 1285110 TI - High prevalence of tuberculin sensitivity. PMID- 1285111 TI - A water contamination incident. PMID- 1285112 TI - Nosocomial transmission of tuberculosis in AIDS care centres. AB - Outbreaks of tuberculosis in centres for the care of patients with AIDS, including outbreaks involving drug-resistant strains of Mycobacterium tuberculosis, have been reported from a number of countries and present special problems. Transmission of infection may be facilitated by procedures commonly used with AIDS patients, and recognition of the diagnosis in an infectious case may be delayed. Although no similar outbreaks have been identified in the United Kingdom, it may be timely to review the policy and procedures used in this country in the light of experience elsewhere. PMID- 1285113 TI - Campylobacter surveillance. PMID- 1285114 TI - Pseudobacteraemia and contaminated ESR bottles. PMID- 1285115 TI - Immunisation against Haemophilus influenzae type b. PMID- 1285116 TI - The diagnosis of hepatitis A in travellers. PMID- 1285117 TI - Salmonella typhimurium DT 49. PMID- 1285119 TI - Sporadic cases of meningococcal disease in schools. PHLS Meningococcal Infections Working Group. PMID- 1285118 TI - Supplies of pneumococcal vaccine. PMID- 1285120 TI - Hepatitis B associated with an acupuncture clinic. PMID- 1285121 TI - Surveillance of Clostridium difficile infection. PMID- 1285122 TI - Hepatitis B and health care workers. PMID- 1285123 TI - Poliomyelitis update. PMID- 1285124 TI - The global problem of malaria. PMID- 1285126 TI - Translational control by poly(A) elongation during Xenopus development: differential repression and enhancement by a novel cytoplasmic polyadenylation element. AB - One characteristic of oocyte maturation and embryogenesis in Xenopus laevis is the activation of translationally repressed (masked) maternal mRNAs by cytoplasmic poly(A) elongation. At maturation, poly(A) elongation is controlled by two cis-acting elements in the 3'-untranslated regions (UTRs) of responsive mRNAs, the hexanucleotide AAUAAA and the cytoplasmic polyadenylation element (CPE), consisting of UUUUUAU or other similar sequences. To investigate poly(A) elongation and translational activation during embryogenesis, we have focused on Cl2 RNA, a representative transcript that undergoes these processes. By injecting radiolabeled Cl2 RNA into fertilized eggs and allowing development to proceed, we found that maximal polyadenylation of this RNA is reached by the 4000-cell blastula stage and that it requires two cis-acting elements, the hexanucleotide AAUAAA and a novel CPE, which is dodecauridine. Interestingly, a shortening of the distance between the two elements changes the timing of maximal polyadenylation to the four-cell stage. The injection of a chloramphenicol acetyl transferase (CAT)-Cl2 chimeric RNA into fertilized eggs not only results in embryonic polyadenylation of the transcript but also 5- to 15-fold more CAT activity compared with eggs injected with CAT RNA or CAT-Cl2 chimeric RNA that is prevented from undergoing poly(A) elongation by a mutation in the polyadenylation hexanucleotide. However, eggs injected with a CAT-Cl2 chimeric RNA that is preadenylated but that cannot undergo further poly(A) elongation contain no more CAT activity than eggs injected with the same RNA without a poly(A) tail, suggesting that the process of poly(A) elongation, and not poly(A) tail length, is important for translation. Finally, we show that precocious poly(A) elongation of Cl2 RNA during oocyte maturation is prevented by a large "masking" element that includes the dodecauridine CPE. The dual role of the CPE in both repression and activation of poly(A) elongation is discussed. PMID- 1285125 TI - U1 snRNP targets an essential splicing factor, U2AF65, to the 3' splice site by a network of interactions spanning the exon. AB - A description of cellular factors that govern alternative splicing of pre-mRNA is largely incomplete. In the case of the rat preprotachykinin gene, splicing of the alternative exon E4 occurs by a poorly understood mechanism in which exon selection is under the positive control of U1 snRNP. Because the binding of U1 snRNP to the 5' splice site of E4 is coincident with the selection of the 3' splice site of E4, this mechanism would appear to involve interactions that bridge across the exon. In this work, a UV cross-linking strategy was used to identify possible RNA-protein interactions involved in the proposed exon-bridging model. Of particular interest is a prominent 61-kD protein, p61, that binds to the 3' splice site of E4 in a manner that is clearly facilitated by a downstream 5' splice site and U1 snRNP particles. The identity of p61 is the essential splicing factor U2AF65, on the basis of copurification and selective binding to polypyrimidine tracts. These results indicate a model in which exon selection is positively regulated by the communication of U1 snRNP and U2AF65. That is, a natural deficiency in binding U2AF65 to the 3' splice site that leads to exon skipping might be overcome by a mechanism in which U1 snRNP facilitates the binding of U2AF65 through a network of template-directed and exon-bridging interactions. PMID- 1285128 TI - [Synthesis, structure and function of alpha-fetoproteins and their importance in medicine]. AB - Alpha-fetoprotein (AFP) is a specific glycoprotein which is synthesised in the fetal liver and released into the blood stream together with the closely related protein, albumin. It has been proposed that AFP functions as a carrier of essential fatty acids to certain developing cells and as a possible immunosuppressor. In man its synthesis is under the strict and complicated control of transcription of a single gene on chromosome 4. The concentration of AFP in fetal serum is greatest at about 13 weeks gestation and then decreases up to birth. During pregnancy AFP passes into the amniotic fluid and also across the placenta, so that the concentration of AFP in maternal serum increases during pregnancy in a characteristic way. Greater than normal increases may indicate certain pathological states in the fetus. Serum concentrations of AFP in the newborn infant decrease rapidly to reach levels typical for adults (< 10 micrograms/L) usually by the end of the first year. Raised concentrations of serum AFP appear in a large proportion of patients with primary hepatoma and in a smaller percentage of patients with other malignant diseases (tumours of the testis, ovary, bronchi, gastrointestinal tract). In addition, increases in serum AFP are found in other illnesses accompanied by damage to hepatocytes in the liver (hepatitis, cirrhosis etc.). Certain differences in the structure of the oligosaccharide portion of the molecule have been shown between AFP synthesized by benign or by malignant cells and between AFP synthesised by hepatocytes or by cells of endodermal origin. These differences have been used as an aid in the diagnosis of liver diseases where serum AFP is elevated. Since AFP is not strictly specific for a certain type of carcinoma, its determination is primarily used in medicine for monitoring the effects of therapy and surgery on the course of malignant conditions which initially showed increased levels of serum AFP. PMID- 1285127 TI - Ribosomal protein L4 and transcription factor NusA have separable roles in mediating terminating of transcription within the leader of the S10 operon of Escherichia coli. AB - Ribosomal protein L4 of Escherichia coli autogenously regulates both transcription and translation of the 11-gene S10 operon. Transcription regulation occurs by L4-stimulated premature termination at an attenuator hairpin in the S10 leader. This effect can be reproduced in vitro but depends on the addition of transcription factor NusA. We show that NusA is required to promote RNA polymerase pausing at the termination site; such paused transcription complexes are then stabilized further by r-protein L4. The L4 effect is observed even if the protein is added after the NusA-modified RNA polymerase has already reached the pause site. Genetically separable regions of the S10 leader are required for NusA and L4 action: The attenuator hairpin is sufficient for NusA-dependent pausing, but upstream elements are necessary for L4 to prolong the pause. PMID- 1285129 TI - Herbal medicine "sho-saiko-to" induces in vitro granulocyte colony-stimulating factor production on peripheral blood mononuclear cells. AB - The herbal medicine "Sho-saiko-to (Xiao-Chai-Hu-Tang)" has been used in China for about 3000 years for the treatment of pyretic diseases. This medicine is now available as one of the prescribing drugs approved by the Ministry of Health and Welfare of Japan, and has also been widely used for patients with chronic viral liver disease as one of biological response modifiers in the field of Japan's Western Medicine. However, its mode of action has not been fully described. In the present in vitro study, we added "Sho-saiko-to" (TJ-9, Tsumura, Tokyo) to the culture of peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers, and observed a dose-dependent increase in the production of granulocyte colony-stimulating factor (G-CSF). The same experiment was conducted using other herbal medicines "Dai-saiko-to" (TJ-8) and "Saiko-keishi-to" (TJ-10) which showed similar effects, or "Sho-seiryu-to" (TJ-19) which consists of very different compounds and shows different efficacy. The increases of G-CSF production were similar when "Sho-saiko-to" (TJ-9) or one of the 2 reference drugs (TJ-8 and 10) was added, whereas the increase when the control drug "Sho seiryu-to" (TJ-19) was added, was quite small. This result shows that G-CSF induction is not a common effect of herbal medicines, but a specific effect of TJ 8, 9, and 10. Among these 3 drugs the increase produced by "Sho-saiko-to" was the largest. Based on this result, we conclude that administration of "Sho-saiko-to" may be useful not only for the treatment of chronic liver disease, but also for malignant diseases and acute infectious diseases where G-CSF is efficacious. PMID- 1285130 TI - Natural killer cell frequency and function in patients with monoclonal gammopathies. AB - We evaluated the frequency and the functional activity of peripheral blood mononuclear cells (PBMCs) with natural killer (NK) cell phenotype in patients with monoclonal gammopathies. CD16+ and CD56+ PBMCs were strongly increased in monoclonal gammopathies of undetermined significance (MGUS) and multiple myeloma (MM). Furthermore, increased frequency of CD16+/CD3+ PBMCs was found in 7/15 patients with MGUS, indicating that T lymphocytes with NK-like phenotype are expanded in at least a subset of these patients. However, despite the increased frequency of PBMCs with natural killer phenotype, the functional NK activity was as comparable in both MGUS and MM patients as in normal individuals. The discrepancy between the expansion of circulating NK cells and the normal NK activity in patients with monoclonal gammopathies requires further investigation. However, at least in some MGUS patients, this discrepancy could be accounted for by the expansion of PBMCs with the rare phenotype CD16/CD3 which have been reported not to mediate significant NK activity. PMID- 1285131 TI - [Endoscopic surgery in neoplasms of Vater's ampulla]. AB - Twenty patients with tumors located in the ampulla of Vater underwent an endoscopic papillo-sphincterectomy. Four of them were palliative procedures and 16 were curative. The patients complaints were: obstructive jaundice, pain on the right hypochondrium, digestive hemorrhage or neoplastic syndrome. The mean age was 72.6 years ranging from 54 to 87. Ten were males and 10 females. The overall mean survival was 36.2 months (S.E.+ - 5.6) ranging between 9 and 50 months. The actuarial survival 18 months after the procedure was 63.5% (S.E.+ - 13%). The survival correlated with the macroscopic shapes according to Tasaka. A comparative analysis was made between the results obtained with palliative endoscopic surgery and radical open surgery. PMID- 1285132 TI - The British Paediatric Surveillance Unit: activities and developments in 1990 and 1991. AB - The British Paediatric Surveillance Unit is a joint undertaking of the British Paediatric Association, the PHLS Communicable Disease Surveillance Centre and the Department of Epidemiology at the Institute of Child Health, London. It provides an active case reporting system which aims to facilitate the surveillance of rare childhood infections and other conditions. Cards with a menu of up to twelve reportable disorders are sent monthly to more than 1100 paediatricians throughout the United Kingdom and Ireland. The average response rate is 90%. Reported cases are followed up according to study protocols. Since its inception in 1986, the Unit has facilitated the study of a wide range of disorders, including HIV infection and AIDS, Reye's syndrome, Kawasaki disease, congenital rubella, neonatal herpes, congenital toxoplasmosis and acute rheumatic fever, and the number of new applications for surveys has increased in 1992-3. Several European paediatric organisations have expressed interest in setting up similar schemes in their own countries. PMID- 1285133 TI - Influenza surveillance in England and Wales: November 1991-June 1992. PMID- 1285134 TI - The epidemiology of pertussis in England and Wales. AB - Recovery in the uptake of whole-cell pertussis vaccine from 30% in 1978 to 91% in 1992 has resulted in a major reduction in the incidence of pertussis and in the proportion of cases occurring in pre-school children. This has been accompanied by a decline in pertussis mortality rates, with no deaths reported since September 1990. Seventy-four per cent of the 50 fatal cases reported since 1980 have been infants under one year of age, demonstrating the importance of completing primary immunisation as early as possible after birth. There is no evidence, as yet, that introduction of the accelerated immunisation schedule in June 1990 has reduced the proportion of cases occurring in infants, suggesting that the decline in mortality during the last two years is largely due to indirect protection provided by the current high level of vaccine-induced herd immunity. If 90% coverage is sustained and there is no significant waning of immunity with age, the circulation of Bordetella pertussis should be sufficiently reduced to interrupt the four year epidemic cycle for the first time in the United Kingdom. The hypothesis that vaccine-induced immunity has a serotype specific component is supported by recent changes in serotype prevalence which have followed the increase in vaccine coverage. Given the successful reinstatement of whole-cell vaccine in the UK immunisation programme, the case for replacing it with a new acellular preparation will require careful evaluation. PMID- 1285135 TI - Serotype specificity of vaccine-induced immunity to pertussis. AB - Two large epidemics of pertussis occurred in Britain during 1977-79 and 1981-83, following a decline in vaccine uptake in the mid-1970s. Serotype 1,3 predominated during both epidemics but serotypes 1,2 and 1,2,3 constituted 32% (243 of 769) of the isolates from unvaccinated children compared with only 10% (9 of 86) of the isolates from vaccinated children (p < 0.005). Whole-cell vaccines, although effective against infection with all serotypes, have a higher efficacy against serotypes 1,2 and 1,2,3 than against serotype 1,3. These data suggest that not only should acellular vaccines contain agglutinogens specific for each serotype but trials should demonstrate efficacy against all three serotypes. PMID- 1285136 TI - The surveillance of communicable disease in the European Community. AB - This article summarises the existing international structures in Europe which collate data produced by surveillance systems in individual countries. The surveillance of influenza, tuberculosis, and other infections in Europe is undertaken by the World Health Organisation (WHO), the European Community (EC), and national and international organisations set up to study specific diseases. The surveillance of foodborne infections, rabies, travel-associated legionellosis and AIDS/HIV is undertaken by WHO collaborating centres or WHO/EC programmes. Research into immunisation and sexually transmitted diseases other than HIV is carried out through EC concerted action programmes. The Maastricht treaty, if ratified, may lead to changes in the way communicable disease surveillance is undertaken in the EC. PMID- 1285137 TI - Food safety: action to protect the consumer. AB - Food safety issues have been headline news frequently in recent years. A review of food legislation was started in 1984 and led to the Food Safety Act 1990. This Act, which may prove to be the last major piece of independent British food law, provides food authorities with new powers to prevent the distribution of contaminated food and ensure that proper practices are being carried out by food businesses, and establishes a registration system for food businesses. Other developments include a new system for the inspection of food premises and plans to introduce a requirement for hygiene training for food handlers. The process of European harmonisation will require a further series of changes--forthcoming proposals provide for quality standards for laboratories, and more frequent inspection requirements covering a wide range of products. PMID- 1285138 TI - Advice for travellers. PMID- 1285139 TI - Surveillance of HIV infection by voluntary testing in England. AB - Eighteen laboratories, which together provide primary HIV antibody testing for 43% of the population in England, collaborated in a study to record epidemiological information for all individuals voluntarily tested by them over a five year period. From the 184,113 individuals who had a first test during the study period, it is estimated that 1 in 12 adults in London, and 1 in 50 outside London have been voluntarily tested for HIV since testing became widely available in 1985. The majority of those tested were individuals whose perceived risk was heterosexual exposure. Infection in this group was concentrated in individuals whose partner had an identified risk and in those who had lived in or visited Africa. The rise in antibody prevalence observed in the latter group during 1990/91 may have been partly due to infection recently acquired in the UK. Antibody prevalence in heterosexuals without a high risk partner or a history of exposure abroad also rose during the study period, suggesting a recent increase in transmission through casual heterosexual exposure in the UK. The study also provided strong evidence of continuing high risk behaviour among homosexual men, particularly in the younger age groups. Homosexuals aged under 30 years and living in London had the greatest risk of acquiring HIV infection since 1988. PMID- 1285140 TI - From the briefcase to the bookshelf: information sources for communicable disease control. PMID- 1285141 TI - 'COVER' (cover of vaccination evaluated rapidly): 22. PMID- 1285142 TI - Listeriosis surveillance. PMID- 1285143 TI - Pilgrimage to Mecca (Hajj) 1992. PMID- 1285144 TI - Tumbu fly infestation. PMID- 1285145 TI - Salmonella enteritidis PT 8 and turkey meat. PMID- 1285146 TI - Salmonella typhimurium DT 203 update. PMID- 1285147 TI - Corynebacterium diphtheriae, skin ulcers and travel abroad. PMID- 1285148 TI - Regulation of HIV testing kits. PMID- 1285149 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285150 TI - Rotavirus surveillance and cluster detection. PMID- 1285151 TI - Salmonella typhimurium DT 141. PMID- 1285152 TI - Issue of human normal immunoglobulin. PMID- 1285153 TI - Leishmaniasis and the Arabian Gulf. PMID- 1285154 TI - Hepatitis A vaccine. PMID- 1285155 TI - Q fever in the Isle of Wight. PMID- 1285156 TI - Dysentery due to Shigella infection. PMID- 1285157 TI - Cryptosporidium surveillance. PMID- 1285158 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285159 TI - Measles surveillance. PMID- 1285160 TI - Salmonella saint-paul. PMID- 1285161 TI - HIV infection in a surgeon. PMID- 1285162 TI - Occupational exposure to HIV and use of zidovudine. PMID- 1285163 TI - Influenza surveillance. PMID- 1285164 TI - Antibiotic-resistant pneumococci. PMID- 1285165 TI - Swine influenza. PMID- 1285166 TI - Non-toxigenic Corynebacterium diphtheriae var gravis. PMID- 1285167 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285168 TI - Congenital toxoplasmosis. PMID- 1285170 TI - Guinea-worm disease. PMID- 1285169 TI - Transmission of HIV infection in the health care setting. PMID- 1285171 TI - A case of cutaneous diphtheria. PMID- 1285172 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285173 TI - Influenza update. PMID- 1285174 TI - Clostridium difficile infection in Manchester. PMID- 1285176 TI - Infant HBV immunisation. PMID- 1285175 TI - Water contamination incident. PMID- 1285177 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285178 TI - Virological surveillance of influenza A. PMID- 1285179 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285180 TI - Salmonella typhi in tower hamlets. PMID- 1285181 TI - Vaccine associated poliomyelitis. PMID- 1285183 TI - Influenza update. PMID- 1285182 TI - Clostridium difficile in London and Staffordshire. PMID- 1285184 TI - Salmonella typhimurium DT 203 in West Yorkshire. PMID- 1285185 TI - A nosocomial outbreak of Streptococcus pneumoniae infection. PMID- 1285186 TI - Influenza. PMID- 1285187 TI - An outbreak of foodborne Shigella sonnei infection. PMID- 1285188 TI - Methicillin-resistant Staphylococcus aureus (MRSA). PMID- 1285189 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285190 TI - Laboratory-acquired meningococcal infection. PMID- 1285192 TI - Travel-associated cholera. PMID- 1285191 TI - Shellfish-associated illness. PMID- 1285193 TI - Early intervention program (EIP)--the Indian experiences. PMID- 1285194 TI - Early intervention program for high risk babies--use of infant motor screen. PMID- 1285195 TI - Regulation of muscle gene expression in Crustacea over the moult cycle. AB - Muscle growth in Crustacea may occur during specific stages of the moult cycle, focused around ecdysis when the old cuticle is shed and the new cuticle expands. In order to determine the moult stages in which sarcomeric proteins are synthesized and the regulatory factors involved, actin mRNA levels have been measured in the muscles of two crustaceans. These levels have been followed throughout the moult cycle and in response to passive stretch of walking leg muscle in vivo and to exogenous ecydsteroids applied to muscle preparations in vitro. Actin mRNA levels in both claw and leg muscles were elevated during the pre and postmoult stages of the moult cycle. However, varying patterns of expression are found in claw and leg muscle at specific stages of pre and postmoult. There was no increase in actin mRNA expression in extensor leg muscles in vitro after 6 hours exposure to elevated premoult levels of ecdysteroids. Immobilization of intemoult walking legs to maintain the extensor muscle in continuous passive stretch did not result in increased levels of actin mRNA after 5 days. These results are discussed in relation to the regulation of muscle growth over the moult cycle and to the molecular processes which may be responsible for controlling muscle protein synthesis. PMID- 1285196 TI - The cytoplasmic translational inhibitory RNA of chick embryonic muscle: cloning and sequence of a subspecies which is antisense RNA. AB - A cytoplasmic translation inhibitory ribonucleoprotein (iRNP), about 10-12S in size and containing a heterogeneous class of RNA (iRNA) in the 60-140 nucleotide size range, has been previously isolated from 13-14 day old chick embryonic leg and breast muscle. Both iRNA and iRNA are potent inhibitors of mRNA translation in vitro. A cDNA library for iRNA was prepared in pUC18 vector. The 114 nucleotide insert of one clone was subcloned in pBluescript vector. The in vitro transcript of this insert (only the 5'-3' orientation and not the reverse orientation) showed inhibition of muscle poly(A)+ mRNA translation in vitro. The derived sequence of the iRNA indicates that it is a new sequence in which 27 nucleotides at the 3' and 5' ends can form base paired stem. Hybridization experiments and sequence analysis indicate that this iRNA has complementary (antisense) sequence to a highly conserved domain of the 28S eukaryotic rRNA and to a 5' leader segment of a muscle mRNA. These results suggest that iRNA mediated translational inhibition may act as a novel mechanism of controlling cellular mRNA levels in embryonic muscle and thus, acts in conjunction with the transcriptional control of myogenesis. PMID- 1285197 TI - Isolation and functional comparison of Dmyd, the Drosophila homologue of the vertebrate myogenic determination genes, with CMD1. AB - We have isolated a cDNA clone, called Dmyd for Drosophila myogenic determination gene, from a 0-16 hour Drosophila embryo library that encodes a protein with structural and functional characteristics similar to the members of the vertebrate MyoD family (Paterson et al 1991). Dmyd encodes a polypeptide of 332 amino acids with 82% identity to MyoD in the 41 amino acids of the putative helix loop-helix region and 100% identity in the 13 amino acids of the basic domain proposed to contain the essential recognition code for muscle specific gene activation. The gene is unique and maps to 95A/B on the right arm of the third chromosome. Low stringency hybridizations indicate Dmyd is not a member of a multigene family, similar to MyoD in vertebrates. Dmyd is a nuclear protein in Drosophila, consistent with its role as a nuclear gene regulatory factor, and is proposed to be a transiently expressed marker for a unique subset of muscle founder cells. We have used an 8kb promoter fragment from the gene, which contains the first 55 amino acids of the Dmyd protein, joined to lac Z to follow myogenic precursor cells into muscle fibers using antibodies to beta galactosidase and Dmyd. Unlike the myogenic factors in vertebrate muscle cells, Dmyd appears to be expressed at a much lower level in differentiated Drosophila muscles so it cannot be followed continuously as a muscle marker. This is reflected in the loss of expression of Dmyd RNA in 12-24 hour embryos, a major period of early myogenesis, as well as in the undetectable level of the nuclear antigen in primary cultures of embryonic and adult Drosophila muscle. Functional differences between Dmyd and CMD1 are described and explained in terms of a model which may give insight to the nature of homo and heterodimer formation in the bHLH family of proteins. PMID- 1285198 TI - Histamine dependence of pentagastrin-stimulated gastric acid secretion in rats. AB - Does gastrin stimulate gastric acid secretion by direct action on oxyntic cells, by releasing histamine, or by being potentiated by histamine? Previous studies in the mouse pointed to gastrin-regulated histamine release. Guinea pig and rat are well known to vary in their sensitivity to histamine. Therefore, the effects of histamine and pentagastrin were compared quantitatively on isolated, lumen perfused, stomach preparations from these species in the absence and presence of histamine H2-receptor blockade. The loss of potency of histamine in the rat was mirrored by a loss of potency of pentagastrin consistent with the idea that pentagastrin acts by releasing histamine. In the rat, a well-defined pentagastrin curve was obtained in the presence of histamine H2-receptor block as though pentagastrin acts both directly on the oxyntic cell and indirectly by releasing histamine. It was not necessary to invoke a potentiating interaction between histamine and pentagastrin at the oxyntic cell; the two effects appeared simply to add. Potentiation was observed, however, between other combinations of stimuli, for example, between vagal nerve and pentagastrin stimulation. The physiological consequences of these results are discussed. PMID- 1285200 TI - [Endoscopic palliative treatment of malignant bile duct obstruction by endoprosthesis]. AB - Endoscopic positioning of a large biliary endoprosthesis has become a well codified procedure for palliative treatment of primary or metastatic malignant bile duct obstruction. Authors' experience, regarding 47 patients treated by this technique from February 1992, is reported. Furthermore, either absolute or site related per cent rate of successful positioning of endoprosthesis, efficacy of procedure, early and late complications and mean survival are reported. Results confirm the effectiveness of the procedure in reducing jaundice resulting from malignant bile duct obstruction and low complication rate; early detection and treatment of prosthetic obstruction with subsequent cholangitis, that is the most important factor responsible for death, depend upon close collaboration between physician and endoscopist. PMID- 1285199 TI - Regulation of histamine release from oxyntic mucosa. AB - The regulation of histamine release from oxyntic mucosa is complex because of two potential sources of histamine: mast cells and enterochromaffin-like (ECL) cells. A gastrin-responsive histamine pool was identified in the rat oxyntic mucosa two decades ago, but these ECL cells from the rat have not yet been isolated or characterized in vitro. In vivo studies in canine and human mucosa have been more difficult because of the high content of histamine in mast cells. Using enzyme dispersed canine oxyntic mucosal cells, we have studied regulation of histamine release from a mast cell-depleted fraction prepared by sequential elutriation and density gradient. Histamine-like immunoreactivity was demonstrated, using peroxidase-anti-peroxidase immunohistochemistry. After short-term culture, histamine was released in response to gastrin, cholecystokinin, carbachol, and forskolin. Somatostatin potently and effectively inhibited the response to gastrin. The cultures used for these studies also contained somatostatin cells, and, furthermore, the response to gastrin was enhanced by incubation with monoclonal antibodies to somatostatin. The latter findings suggested that somatostatin was acting in these cultures by a paracrine route. This pattern contrasts with that obtained in previous studies of canine oxyntic mucosal mast cells. PMID- 1285201 TI - Palliation of malignant bile duct obstruction: our experience with endoscopic 14 French prostheses. AB - We evaluated the efficacy of wide 14F endoprostheses endoscopically placed in en patients with malignant extrahepatic bile duct stenosis. Large-bore stents were successfully placed in all patients. There were no early complications. Stent clogging occurred in two patients after one month and after three months in another patient. Seven patients remained free of symptoms after a mean follow-up period of 4.5 months. PMID- 1285203 TI - Salmonella java and tropical aquaria. PMID- 1285204 TI - Sexually transmitted diseases and HIV infection. PMID- 1285202 TI - [Endoscopic recanalization with alcohol in the treatment of dysphagia of neoplastic origin]. AB - Nineteen patients with dysphagia were treated by endoscopic injection of ethanol, to induce tumoral necrosis. Dysphagia was present in patients with inoperable, unresectable or recurrent esophagogastric cancer. Prior treatment, patients had a mean dysphagia grade of 3.22. After the first session, they had a mean of 2.05. An optimum dysphagia grade mean was 1.47. The period intertreatment was X 45 days. There were no complications associated with the method. The results suggest this therapy is a good palliative procedure that, in a short time and with a low cost, can improve the life quality in selected patients. PMID- 1285205 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285206 TI - Changes in the supply of childhood vaccines. PMID- 1285207 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285208 TI - Progression of the AIDS pandemic. PMID- 1285209 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285211 TI - New guidelines on HIV testing and partner notification. PMID- 1285210 TI - Hepatitis A prophylaxis for haemophiliac patients and other recipients of pooled plasma products. PMID- 1285212 TI - Surveillance of Haemophilus influenzae type b infection. PMID- 1285213 TI - AIDS and HIV-1 infection in the United Kingdom: monthly report. PMID- 1285214 TI - Ventricular arrhythmias in aortic valve disease before and after surgery. AB - In order to evaluate the incidence and prognostic value of ventricular arrhythmias in patients with aortic valve disease, 24 hour ambulatory electrocardiographic recordings were obtained in 374 patients without coronary artery disease (aortic stenosis n = 194, aortic regurgitation n = 103, combined aortic stenosis and regurgitation n = 77). Following aortic valve replacement, repeat recordings were obtained in a subgroup of 96 patients at 13 +/- 4 days and 18 +/- 7 months. Ventricular arrhythmias were classified in all cases according to Lown and were compared with clinical, echocardiographic and hemodynamic data. Preoperatively, ventricular premature beats were observed in 329 patients (88%), and were found to be frequent (>30 ventricular premature beats/hour) in 83 (22%). Multiformity was found in 105 (28%), couplets in 75 (20%) and ventricular tachycardia in 45 (12%). The occurrence of ventricular arrhythmias was not related to the type or severity of the valve lesions. Patients with severe ventricular arrhythmias (Lown class 3 or 4: 36.5%) had a higher ventricular wall thickness (interventricular septum thickness 14.2 +/- 1.8 mm vs. 11.9 +/- 2.0 mm, p < 0.01, a higher LV mass (178 +/- 32 g/m2 vs. 142 +/- 35 g/m2, p < 0.001) and a lower left ventricular ejection fraction (48% +/- 9% vs. 56.5% +/- 10%, p < 0.001); while in patients with aortic regurgitation a higher end-diastolic LV volume (224 +/- 38 ml/m2 vs. 178 +/- 42 ml/m2, p < 0.02) and a higher end systolic LV diameter (56 +/- 7 mm vs. 46 +/- 8 mm, p < 0.02) were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285215 TI - Correlation of epidermal growth factor receptor and c-erbB2 oncogene product to known prognostic indicators of colorectal cancer. AB - Both epidermal growth factor receptor (EGFr) and the oncogene product of c-erbB2 have been shown to be expressed by human malignancies, and in some cases to relate to clinical outcomes. This study investigates the correlation between the presence of these receptor proteins and known prognostic indicators of colorectal cancer. Indirect immunoperoxidase staining of 32 freshly frozen surgical specimens revealed an overall expression of EGFr and c-erbB2 of 43% and 38%, respectively. A significantly higher rate of EGFr expression was found in tumours of more advanced stage (Dukes C and D), poor differentiation and those exhibiting vascular and lymphatic invasion. The presence of the c-erbB2 protein did not correlate with any of these variables. Expression of these molecules appeared to be independent and positive staining for both receptors occurred in only 19% of cases. EGFr may play a future role as a prognostic tool in colorectal cancer. PMID- 1285216 TI - Differential immunoreactivity of her-2/neu oncoprotein in prostatic tissues. AB - To investigate HER-2/neu oncoprotein immunoreactivity, monoclonal antibody TA1 immunohistochemical examination of flash-frozen radical prostatectomy specimens was performed (n = 35). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or prostatic intraepithelial neoplasia (PIN), as well as prostatic carcinoma (CaP). HER-2/neu oncoprotein immunoreactivity in BPH tissues was not significantly different than that for the PIN basal cell layer (P = 0.10) or for the PIN luminal cells (P = 0.17). There was significantly more HER-2/neu oncoprotein immunoreactivity in BPH than in areas of CaP (P < 0.001). There was no significant difference in the amount of immunoreactivity present in PIN basal cells when compared to the PIN luminal cells (P = 0.49). Both the PIN basal cells and luminal cells stained for the HER-2/neu oncoprotein to a higher degree than cells in the CaP areas (P < 0.001 in both cases). HER-2/neu oncoprotein immunoreactivity is present at a significantly higher degree in BPH and PIN than in malignant prostatic epithelium. PMID- 1285217 TI - Is the relationship between angiogenesis and metastasis in breast cancer real? AB - The suggested link between angiogenesis in breast cancer and metastasis remains unsubstantiated. We tested this relationship in primary breast carcinomas from 37 patients with a median follow-up 9.5 years (Cohort 1) and 50 patients with a median follow-up of 1.5 years (Cohort 2). Angiogenesis was assessed by counting vessel density after immunohistochemical staining of vascular endothelium for factor VIII. Patients were grouped according to whether metastasis (defined as spread to axillary lymph nodes, distant sites or both) had occurred. The mean +/- SD scores in Cohort 1 when metastasis was absent and present, respectively, were 15.6 +/- 4.9 (n = 21) and 14.1 +/- 3.7 (n = 16). In Cohort 2 the scores were 15.4 +/- 5.8 (n = 26) and 14.5 +/- 4.9 (n = 24). There was no significant difference between these scores in either cohort. Multivariate analysis demonstrated lymph node involvement (P < 0.001) and tumour size (P < 0.001) but not angiogenesis score (P > 0.05) to predict distant metastasis. This evidence argues against any prognostic significance of angiogenesis in breast carcinoma. PMID- 1285218 TI - [Ex situ-in vivo hepatic resection. Technique and initial results]. AB - Extracorporeal liver surgery has been proposed with the aim to increase the resectability rate in patients with advanced tumors. In order to avoid the inherent section of the hepatic pedicle we propose ex situ-in vivo liver surgery. The surgical procedure comprises complete mobilization and exteriorization of the liver which is rocked on the axis of the porta hepatis following section of the hepatic veins. Protection of the liver parenchyma against prolonged ischemia is obtained through cold portal perfusion (UW solution) and the use of an heat exchanger on which liver resections and vascular procedures are performed. The procedure also encompasses the use of veno-venous bypass during liver vascular exclusion. This procedure was performed in 2 patients with tumoral invasion of the 3 main hepatic veins and in 1 patient whose hemangioma was surrounding the hepatocaval confluence. Duration of hypothermic ischemia was 205, 225 and 230 minutes respectively. Postoperative course was uneventful in the 3 cases with an hospital stay of 25, 28 and 18 days. Ex situ-in vivo liver surgery allows completion of a surgical treatment in patients whose tumor appears unresectable with the use of conventional technics. This procedure may constitute an alternative to liver transplantation in highly selected cases. PMID- 1285219 TI - Antibody-directed therapy of multidrug-resistant tumor cells. AB - The major obstacle to effective cancer chemotherapy is the resistance of tumor cells to cytostatic agents. Tumor cells frequently express a multidrug-resistance (MDR) phenotype. In an effort to devise new strategies to overcome MDR, antibody directed approaches for the eradication of MDR cells have been developed. Experimental data have shown that multidrug-resistant tumor cells can be efficiently killed by monoclonal antibodies, immunotoxins, or bispecific antibodies. The current experimental results indicate that an antibody-directed therapeutic approach to eradication of MDR cells might be a promising adjunct to conventional chemotherapy of cancer patients. PMID- 1285220 TI - [The surgical treatment of cancer of the proximal extrahepatic bile ducts]. PMID- 1285221 TI - Deficiency of CD4+CD45RA+ lymphocytes in patients with glioblastoma multiforme. PMID- 1285222 TI - Endolaparoscopic palliation of pancreatic cancer. AB - Two patients with advanced pancreatic cancer were palliated for both duodenal and biliary obstruction without laparotomy. The techniques of endoscopic biliary stent and laparoscopic gastrojejunostomy are described. This combination achieved rapid palliation with minimum morbidity. Patients with advanced pancreatic cancer and a limited life expectancy benefit greatly from the shortened hospital stay and convalescence this manner of treatment offers. PMID- 1285223 TI - Sexually transmitted diseases in England and Wales: 1981-1990. AB - Data provided by genito-urinary medicine clinics, microbiology laboratories and other reports reveal a consistent picture of the epidemiology of sexually transmitted diseases in England and Wales during the 1980s. The number of new cases increased by 21% between 1981 and 1990; most of this increase being due to genital herpes, genital warts and 'non-specific genital infection' (including that due to Chlamydia trachomatis). The increase in attendance rates for new cases was much higher for women (37%) than for men (2%) during the last decade, with the former experiencing more sequelae. Gonorrhoea and syphilis declined steadily until 1989 but cases of gonorrhoea have increased since then, especially in homosexual males. These data emphasise the need for renewed efforts toward the prevention and control of sexually transmitted diseases, particularly among adolescents, women and homosexual men. PMID- 1285224 TI - 'COVER' (cover of vaccination evaluated rapidly): 20. PMID- 1285225 TI - Bacterial infection and human cancer: association or causation? AB - Environmental factors such as diet, industrial pollution, smoking and viruses account for some 80% of cancers and more than one-quarter of all non-accidental deaths. Little attention has been paid to the relationship between bacterial infection and cancer but there is growing evidence to support this link. For some sites, such as stomach and colorectum, the evidence is relatively strong, whereas for others, such as biliary tract and bladder, it is more circumstantial. PMID- 1285226 TI - Illness associated with eating oysters. PMID- 1285227 TI - Occupationally acquired zoonotic infections. PMID- 1285228 TI - Legionnaires disease in Grimsby. PMID- 1285229 TI - Salmonella panama in the West Midlands. PMID- 1285230 TI - Toxins associated with Japanese shellfish. PMID- 1285232 TI - Escherichia coli O 157. PMID- 1285231 TI - A choice of typhoid vaccines. PMID- 1285233 TI - Vancomycin-resistant enterococci. PMID- 1285234 TI - Echovirus surveillance. PMID- 1285235 TI - ICD-10. PMID- 1285236 TI - Listeriosis in France. PMID- 1285237 TI - Malaria deaths in the United Kingdom. PMID- 1285238 TI - Typhoid fever in east London. PMID- 1285239 TI - Immunisation against infectious disease: 1992 edition. PMID- 1285240 TI - Two space-time Salmonella clusters. PMID- 1285241 TI - Changes at the Central Public Health Laboratory. PMID- 1285242 TI - Salmonella kedougou and cooked meats. PMID- 1285243 TI - Benign prostatic hyperplasia. Its natural history, epidemiologic characteristics, and surgical treatment. AB - Benign prostatic hyperplasia is a nonmalignant enlargement of the prostate that is due to both epithelial and stromal hyperplasia. Although the exact origin of this condition is not well defined, it is thought to arise as microscopic nodules in the periurethral tissue of the prostate gland as early as the late '20s. With advancing age and the presence of androgens, this histologically identifiable hyperplastic tissue progresses to a macroscopic state, which is a palpably enlarged prostate. This enlarged prostate causes clinically significant obstruction of the bladder outlet in many men, necessitating therapeutic intervention. Currently, prostatectomy is the standard treatment with successful long-term results. Nevertheless, much information has become available recently on its indications, outcomes, associated morbidity and mortality, and effect on quality of life. Because of these findings as well as the rising healthcare costs and the desire among patients to avoid surgery if possible, there is much enthusiasm for developing less expensive, less invasive, but effective treatments for symptomatic benign prostatic hyperplasia. To appreciate the tremendous advances being made with regard to the treatment of benign prostatic hyperplasia, it is necessary to have a complete understanding of the disease process itself and its traditional therapies. This clinical report provides a comprehensive review of the natural history, epidemiologic characteristics, and outcomes of both open and transurethral surgery for benign prostatic hyperplasia. PMID- 1285244 TI - Urinary trypsin inhibitory activity for the diagnosis of bacterial infection: a prospective study in 690 patients. AB - OBJECTIVES: During the acute phase response, interleukin-1 induces production of inter-alpha-trypsin inhibitor. The measurement of urinary trypsin inhibitory activity which results from the effects of inter-alpha-trypsin inhibitor degradation products is easy, quick and inexpensive. We conducted a prospective study to investigate its value as a diagnostic tool in comparison with C-reactive protein. METHODS: Comparisons were made in 690 consecutive patients at admission to a department of internal medicine. RESULTS: The level of urinary trypsin inhibitory activity was significantly higher in patients with bacterial infection (mean = 123 IU/g creatinine) than in patients with either viral infection (34 IU), cancer (50 IU), elevated erythrocyte sedimentation rate without infection (45 IU), miscellaneous non-inflammatory diseases (27 IU) or in non-organic controls (19 IU) (Dunnet's test, p << 0.01). The receiver operating characteristic curve showed that sensitivity and specificity of urinary trypsin inhibitory activity were higher than those of C-Reactive protein for the diagnosis of bacterial infection. For levels > or = 60 IU, sensitivity was 75% and specificity 89%. Urinary trypsin inhibitory activity levels fell within 2 days in patients treated for acute bacterial infection. CONCLUSION: Urinary trypsin inhibitory activity could be a useful marker of bacterial infection particularly in patients with fever of unknown origin and/or elevated erythrocyte sedimentation rate. PMID- 1285245 TI - Antibodies to non-structural hepatitis C virus antigens: a link with liver disease activity? AB - OBJECTIVES: The aim of our study was to evaluate the aetiopathogenetic role of hepatitis C virus (HCV) in the genesis of chronic liver disease and hepatocellular carcinoma and the relationship between presence of circulating antibodies against non-structural HCV antigens and disease activity. METHODS: Using a new enzyme-immunoassay capable of detecting, either separately or together, circulating antibodies to structural and non-structural hepatitis C virus antigens, we tested 208 chronic hepatitis B surface antigen (HBsAg) carriers and 144 patients suffering from chronic liver disease. RESULTS: Among the chronic HBsAg carriers with normal transaminase activity, there were 4% who proved to be anti-HVC positive, compared with 14.5% among those with high serum transaminase. Among subjects with chronic liver disease, 20% of patients with chronic persistent hepatitis, 54% with chronic active hepatitis, 35% with liver cirrhosis and 47% with hepatocellular carcinoma proved to be anti-HCV positive. With regard to the aetiology of liver disease, 13% and 25% of chronic HBV infected patients, with or without anti-delta virus superinfection respectively, had anti-hepatitis C virus antibody. This prevalence was 22% among alcoholic liver disease and 89% among patients with cryptogenic liver diseases. The percentage of subjects with circulating antibodies against non-structural HCV proteins was higher among HBsAg chronic carriers with raised alanine aminotransferase and among patients with chronic active hepatitis and hepatocellular carcinoma. CONCLUSIONS: Many subjects with chronic liver disease have circulating anti-HCV antibodies. Anti-HCV positive subjects, especially those with antibodies to non-structural antigens, are more frequently found among patients with aggressive liver diseases. Among HBsAg chronic carriers the prevalence of anti-HCV was lower in "healthy carriers" and HBeAg positive rather than in HBeAg negative subjects with high alanine aminotransferase. We therefore suggest that there may be a relation between HCV replication, activeness of the liver disease and presence of antibodies to non-structural viral antigens. PMID- 1285246 TI - Neonatally administered capsaicin induces functional disturbances in the carotid afferent pathway to the nucleus tractus solitarius. AB - The effect of neonatal capsaicin treatment on chemo- and/or barosensory input to the medulla was studied in 35-40-day-old rats. By means of responses evoked in the nucleus tractus solitarius by stimulating the ipsilateral sinusal nerve, the excitability of slow-conducting carotid afferent fibers and the effect of substance P microinjection into the fourth ventricle were evaluated. Neonatal capsaicin resulted in reduced amplitude of the late component of the evoked responses, increased chronaxie values in the strength-duration paradigm, and increased sensitivity of evoked responses to the inhibitory effect of intracerebroventricular administered substance P. The results indicate that capsaicin given early in life leads to functional disturbances of chemo- and/or barosensory input to the nucleus tractus solitarius, involving both the slow conducting primary afferents and the receptors for substance P of the second order cells of the sensory pathway. PMID- 1285247 TI - 1-Phenyl-3-trimethylaminopropyl carbodiimide: a new inhibitor of thymidylate synthase. AB - Thymidylate synthase (EC 2.1.1.45) from methotrexate-resistant Lactobacillus casei was inactivated by 1-phenyl-3-trimethylaminopropyl carbodiimide (PTC), 1 phenyl-3-dimethyl aminopropyl carbodiimide (PDC), and 1-ethyl-3-dimethyl aminopropyl carbodiimide (EDC). In the presence of excess PTC, the inactivation followed pseudo-first order kinetics; the second order rate constant was approximately 200 M-1min-1 at 30 degrees C. The rate of inactivation by PTC was faster than that by either PDC or EDC. Concentrations of the substrate dUMP greater than 0.15 mM, or of the product dTMP greater than 1.6 mM completely protected the enzyme from inactivation by PTC, but 10 mM dUrd provided very little protection. The rate of inactivation of EDC was reduced by only 40% in the presence of 50 mM dUMP. Nucleophiles (sulfanilic acid, glycine methyl ester, or glycine ethyl ester) had no effect on the rate of inactivation by PTC. The complete inactivation of thymidylate synthase by PTC was accompanied by the incorporation of approximately 2 mols of 14C-PTC per mol of enzyme. Although carbodiimides normally modify carboxyl groups in proteins, results from sulfhydryl group titrations and from reversible modification of sulfhydryl groups by methyl methanethiosulfonate suggest that two of the four cysteine residues of thymidylate synthase were modified by PTC. PMID- 1285248 TI - Kinetics and mechanism of proteinase-binding of pregnancy zone protein (PZP). Appearance of sulfhydryl groups in reactions with proteinases. AB - Proteinase binding by pregnancy zone protein (PZP), an alpha-macroglobulin involves bait region cleavages, association of dimeric-PZP into tetrameric and reaction of internal gamma-glutamyl-beta-cysteinyl thiol esters of PZP with proteinase side chains. The product is an equimolar enzyme-PZP(tetramer) covalently linked complex with four free sulfhydryl groups. The kinetics of the appearances of sulfhydryl groups during the reaction of PZP with chymotrypsin has been investigated using stopped-flow and conventional mixing techniques over a broad concentration range. Thiol ester cleavages followed double exponential decays corresponding with two steps. The faster one resulted in the appearance of three sulfhydryl groups with an observed rate constant, k(obs) = k1.1 + k1.2 delta E, dependent on the excess concentration of chymotrypsin, delta E, and k1.1 = 0.03 s-1 and k1.2 = 4 x 10(4) M-1 s-1. The last sulfhydryl group appeared in a slower step, with similar concentration dependence and k2.1 approximately 0.003 s 1 and k2.2 approximately 5 x 10(3) M-1s-1. Covalent binding of the enzyme apparently was simultaneous with the faster thiol ester cleavage step. Based on these and previous results a model of the reaction mechanism of the proteinase binding reaction of PZP is proposed. It consists of four major steps: (i) Bait region cleavage of PZP-dimers by the enzyme, (ii) fast association of enzyme PZP(dimer) species with native PZP or with another enzyme-PZP(dimer) compound resulting in release of one of the associated enzyme molecules (iii) reaction of an average of three thiol esters of the enzyme-PZP(tetramer) intermediate with the associated internal enzyme molecule or with an external one. In this step one enzyme molecule becomes covalently linked to the PZP-(tetramer), three sulfhydryl groups appear and the enzymic activity of the bound enzyme molecule decreases to the level of that of the final complex. (iv) Hydrolysis of the last thiol ester and in the presence of excess enzyme, degradation of enzyme-PZP(tetramer) complexes and formation of fragments some of which are the size of PZP(dimer) with enzyme bound. PMID- 1285249 TI - Inhibitory effect of aryl thienyl-ketones and -thioketones on arachidonic acid induced malondialdehyde formation in human platelets: biological data and molecular modelling. AB - A series of anti-thrombotic aryl thienyl-ketones and -thioketones was assayed in vitro for their inhibitory effect on malondialdehyde (MDA) production induced by arachidonic acid in human platelets. For several compounds MDA formation was strongly inhibited indicating that the anti-platelet target was situated on the cyclooxygenase pathway. A comparison between the inhibition constant Ki and the IC50 values revealed competitive inhibition kinetics. The molecular structure of one active compound was analysed by X-ray diffraction and theoretical calculations to provide information on its electronic and lipophilic properties. PMID- 1285250 TI - Inhibition of gastric H+, K(+)-ATPase by quercetin. AB - The effects of the naturally occurring flavonoid, quercetin, on gastric H+, K(+) ATPase were investigated. Quercetin inhibited hog gastric H+, K(+)-ATPase and K(+)-stimulated p-nitrophenyl phosphatase (K(+)-pNPPase) activity in a dose dependent manner with IC50 values of 2.3 microM, and 6.0 microM respectively. The inhibition of H+, K(+)-ATPase by quercetin is competitive with ATP and is noncompetitive with K+. The steady-state phosphorylation level of the enzyme was also dose-dependently reduced by quercetin with an IC50 value of 4.5 microM. These results suggest that quercetin reduces the phosphorylated enzyme level by competition with ATP, and thereby inhibits the H+, K(+)-ATPase activity. PMID- 1285252 TI - Algebraic least squares estimates of inhibitor constants. AB - When the data has a constant coefficient of variation, appropriately weighted least squares estimates of the parameters for competitive inhibition in both enzyme and binding experiments can be obtained algebraically. The algorithms are presented and justified. PMID- 1285251 TI - The role of fibrin fibrils in the dissociation of a cell surface protease inhibitor complex and evidence for the recapture of the inhibitor protein. AB - Colonic epithelial cells possess a cell surface protease referred to as guanidinobenzoatase (GB). Active GB can be located by the fluorescent active site directed competitive inhibitor 9-amino acridine (9AA) followed by fluorescence microscopy. The cell surface GB can be transferred to fibrin fibrils, which have a higher affinity for GB than the cell surface. The cytoplasm of colonic epithelial cells contains a protein which inhibits membrane bound GB, forming a latent form of GB or GB-inhibitor complex. This complex can also be dislodged from the epithelial cell surface due to the high affinity of fibrin for GB, with the consequent dissociation of the enzyme-inhibitor complex and solubilisation of the inhibitor. This use of fibrin has led to the demonstration of the transfer of a selective inhibitor protein from one cell surface (the donor) to a second cell surface (the target). PMID- 1285253 TI - Some amines as inhibitors of pea diamine oxidase. AB - The inhibition of pea diamine oxidase (DAO; EC 1.4.3.6) by some amines and chelating agents has been studied. Ethylenediamine (competitive, Ki = 5.2 mmol.l 1), cis-1,2-diaminocyclohexane (noncompetitive, Ki = 2.9 mmol.l-1) and trans-1,2 diaminocyclohexane (competitive, Ki = 3.6 mmol.l-1) are weak inhibitors whereas diethylenetriamine (noncompetitive, Ki = 7.2 mumol.l-1), triethylenetetraamine (partial noncompetitive, Ki = 0.57 mumol.l-1) are potent inhibitors. The chelating agents 1,10-phenanthroline (Ki = 0.031 mmol.l-1), and 2,2'-bipyridyl (Ki = 0.058 mmol.l-1) are noncompetitive inhibitors. The pH-inhibition profile for the inhibitors indicates that the protonated forms are the active species. PMID- 1285254 TI - The conformational analysis of serine protease inhibitors and its applications for drug design. PMID- 1285255 TI - Direct recovery and molecular analysis of DNA and RNA from soil. AB - A simple method for the recovery of DNA and direct detection of nif and Tn5 sequences in soil has recently been presented by Selenska and Klingmuller. On the basis of that method we have developed a procedure for the recovery and separation of DNA and RNA from the same soil sample. A 550 bp sequence from the Kmr gene of Tn5 was identified by PCR amplifications in total DNA and RNA, isolated from soil inoculated with a nitrogen-fixing Enterobacter agglomerans 19 1-1, which carries this transposon. Hence, not only the presence of the Kmr gene of Tn5 but also its expression (mRNA synthesis) in the analyzed environmental samples was detected. The authenticity of the products of PCR amplifications of DNA and mRNA was confirmed by the PhotoGene hybridization technique. PMID- 1285256 TI - Lethal effect of a bait for Rhodnius prolixus (Hemiptera: Reduviidae), the vector of Chagas' disease, containing hexachlorocyclohexane (HCH), under laboratory conditions. AB - The lethal effect of a bait containing an aqueous hexachlorocyclohexane (HCH) suspension at the concentration of 1g/l and maintained at room temperature was studied in the laboratory over a period of 12 weeks. The suspension was placed in a latex bag hanging inside a 1000-ml beaker tightly covered with nylon netting, and left there with no changes for 85 days. Sixteen groups of R. prolixus bugs, consisting on average of 30 specimens each, were successively exposed to the bait and observed at different intervals for one week each. The mortality rate was 100% for all groups, except for the 16th, whose mortality rate was 96.7%. As the groups succeeded one another, mortality started to occur more rapidly and was more marked at the 6- and 24-h intervals. Later tests respectively started at 6:00 a.m. and 6:00 p.m. showed that diurnal and nocturnal periodicity in the offer of food had no effect on mortality. First- and 2nd- instar nymphs and adults male were more sensitive and 5th- instar nymphs were more resistant to the active principle of the bait. PMID- 1285258 TI - [Interferon, interferon inducers, human papillomavirus infection]. PMID- 1285257 TI - [The tumor markers CEA, AFP and CA125 in patients with endometrial carcinoma]. AB - The plasma concentration of CEA, AFP and CA125 in 54 women with endometrial carcinoma and 12 with atypical hyperplasias, were investigated. In 20 of the patients the tumor markers were studied again 11 months after the surgical treatment. Elevation of CEA, AFP and CA125 levels was found in the third, and especially in the forth phase of the illness. Essential similarities between the histological differentiation and the levels of the tumor markers were not observed. The supposition was that the study of the CEA, AFP and CA125 is not a reliable criterion for the early diagnosis of the endometrial carcinoma. They have a prognostic significance only in patients of the second clinical phase after a surgical treatment. It is recommended two of the markers to be used, mostly CEA and CA125 and the study to be performed several times. PMID- 1285259 TI - [Our experience in the prenatal echographic diagnosis of spinal dysraphism in the fetus]. AB - The investigation consists of 141 cases of prenatal diagnosing structural and chromosomal anomalies of the fetus. Seventeen of the cases, quoted above, concern spinal dysraphism (spina bifida, occipital meningocele, meningoencephalocele). It has been made an analysis of ultrasound signs at this group of defects which turned out the most useful for the definite diagnosis. According to the literary survey and author's experience are formed two main groups of indices at echo sounding study--direct and indirect. There have been considered the technics of echoscopy in searching the signs of different terms of pregnancy. It has been made a partial comparison of the reliability in the two groups ultrasound signs with this in biochemical diagnosis of spinal dysraphism in the fetus. PMID- 1285260 TI - [Effect of dietary protein levels on the genesis of repair tissue in rats]. AB - The objective of this study was to verify if the diet protein level affects the genesis of the repair tissue in rats submitted to a poly-chloro-vinyl (PVC) sponge implantation, as well as to analyse the possible alterations in the synthesis of the mucopolysaccharides acids (glucosaminoglycans) by the histophotometry technique. Forty five Wistar weanling male rats, at 21 days of age, were divided into three experimental groups; the groups were fed diets al 6%, 15% and 40% protein level from casein source, during at 69 days period. The animals which received the low protein diet (6%) presented an inhibition in the evolution and maturation of the granulation tissue mainly in the 4th, 7th and 10th days after the sponge PVC implantation. It was also observed that there was less infiltration of the inflammatory cells, less fibroblasts proliferation, reduction of the collagen fibers synthesis, neovascularization decreased and an inhibition of the mucopolysaccharide acids synthesis. PMID- 1285261 TI - [Strategy for monitoring and implementing methods for correcting child growth and development in rural areas of Sonora. Mexico]. AB - An appropriate health technology to facilitate child growth and development in a rural area is presented and documented. Because mother's adequate behavior related to child's care does not produce immediate behavioral or physical changes it is necessary to create a long term social system of consequences. This was achieved joining a longitudinal measurement system with a program to train mothers to identify and deal with health and development issues. During four years, data were collected on weight-length development and morbidity twice a year and simultaneously skills were taught to diagnose treatment and prevent growth and development problems. After the third session child development and anthropometry data became the base of a system to assess maternal behavior, providing consequences for links in the behavior chains associated with child care. This system made organization and participation of the community in primary health care programs more likely, which implied a better score in each child growth and development chart. PMID- 1285262 TI - Some humoral immunological aspects of the rheumatoid arthritis correlated with the ultrastructural changes of the rheumatoid synovial fluid. AB - We performed serologic and synovial investigations in rheumatoid (Latex 1/1280, 1/640, negative and Waaler Rose 1/1024, 1/512, negative), non-rheumatoid and control lots. The immunological results were correlated with ultrastructural changes found in the synovial fluid (SF) at the same titres of rheumatoid factor (RF). The pathologic values of the circulating immune complexes (CIC) (mean = 108.05 U), IgM (mean = 420 UI/ml), IgG (mean = 355.36 UI/ml), and anti-collagen II antibodies (mean = 558.6 U) were present at high titres of RF (Latex 1/1280, Waaler Rose 1/1024). These cases had also major ultrastructural changes of the nucleus and cytoplasm. We inferred from this the implication of the immune factors in the etiology and pathology of the Rheumatoid Arthritis (RA). The high, titres of RF were correlated with pathologic values of the C-reactive-protein (CRP) (mean = 13.31 mg%) and alpha-1-acid glycoprotein (A-1-GA) (mean = 158.3 mg%). The decline of the complement fraction C3 from the synovial fluid in RA confirms the immune character of the rheumatoid synovitis and may be useful in the diagnosis process. The significantly lower concentrations of the protease inhibitors alpha-1-anti-trypsin (A-1-AT) (mean = 165.1 mg%) and alpha-2 macroglobulin (A-2-M) (mean = 129.6 mg%) in synovial fluid suggest a diminution of the anti-proteasic activity due to local immune conflict. PMID- 1285263 TI - Glomerular permeability to macromolecules in gentamicin-treated rats. AB - 1. To determine the effect of gentamicin on the functional properties of the glomerular barrier, 44 Wistar rats received daily doses of 80 mg/kg body weight for 6 days. Glomerular permeability to neutral dextrans and albumin was evaluated by day 6 and albuminuria was determined on the 1st, 3rd and 5th days of treatment. 2. Treatment induced an intense increase in albuminuria from 74 micrograms/24 h to 11.5 mg/24 h on the 5th day of treatment (N = 11). This increase was associated with the presence of large amounts of albumin in elements of the glomerular filter and in the apical region of the proximal tubular cells (N = 4). Fractional clearances of neutral dextrans having molecular radii in the range of 18-41 A were not significantly different in control (N = 5) and gentamicin-treated rats (N = 7). 3. These results show that gentamicin, a polycation at pH 7.4, produces an increase in the glomerular permeability to negatively charged macromolecules in rats, probably due to interaction of the polycation with negative changes in the glomerular filter. PMID- 1285264 TI - Calcium currents in solitary hair cells isolated from frog crista ampullaris. AB - Some properties of Ca2+ currents in hair cells isolated from frog semicircular canals by enzymatic or mechanical treatment were studied by using the whole-cell configuration of the patch-clamp technique. After blocking the large outward K+ currents by substituting Cs+ for K+ and adding tetraethylammonium to the pipette filling solution, voltage- and time-dependent inward currents were clearly detectable in the presence of 4 mM Ca2+ in the extracellular solution. Ca2+ current was recruited at test potentials more positive than -60 mV, showed a rapid activation, and exhibited no inactivation during 150-ms depolarizing pulses. The maximal amplitude was attained at about -20 mV, with an average value of about 80 pA. When Ca2+ in the extracellular solution was replaced with Ba2+, the magnitude of inward currents increased about twofold. Ba2+ currents were blocked more effectively by Cd2+ than by Ni2+, were suppressed by 0.5 microM omega-conotoxin, and were virtually unaffected by amiloride. The dihydropyridine Bay K 8644 caused a marked voltage-dependent increase in inward currents. The present data suggest that hair cells from frog crista ampullaris are endowed with a homogeneous population of Ca2+ channels having several properties similar to those described for neuronal L channels. Since these channels are recruited in a range of potentials close to the resting level, it is suggested that they subserve the control of both resting and evoked transmitter release from the basal pole of the hair cells. PMID- 1285265 TI - Organization of afferent projections to the ventral and dorsal regions of the cat lateral vestibular nucleus: an HRP study. AB - Topical organization of afferent projections to Deiters' nucleus originating from cortical, subcortical, brainstem, and spinal cord structures has been revealed in the cat by microiontophoretic injection of horseradish peroxidase (HRP) into the ventral (NVLV) and dorsal (NVLD) regions of the nucleus and subsequent study of retrograde axonal transport of the enzyme. Differences between afferent inputs to the ventral and dorsal parts of the nucleus, considered as representative of the forelimb and hindlimb regions of the structure, have been observed. The trajectories of labeled fiber systems of the nucleus mentioned have been described. Computer reconstruction of the cat lateral vestibular nucleus (NVL) according the contours drawn from frontal sections of the brain has been carried out. PMID- 1285266 TI - [The laparoscopic management of ectopic pregnancy]. AB - Twenty-five ectopics pregnancies were treated successfully by laparoscopic approach from november 1990 to april 1992. The technics used were: salpingostomy, salpingectomy and taking out trophoblastic tissue exclusively. At the present time, two out of eight women who have wanted become pregnant, have delivered a healthy babies. We concluded that the ectopic pregnancy is efficiently managed by laparoscopy with advantages such as: minimal scar, short time in the hospital, quickly return to total activity, low costs, etc. PMID- 1285267 TI - [The treatment of ectopic pregnancy with local and intramuscular methotrexate or expectant management]. AB - Ten patients with ectopic pregnancy, probably non complicated, diagnosed by transvaginal sonography and serial determinations of subunit B of human chorionic gonadotrophin, were treated with a single injection of methotrexate intraovular (5 cases), intramuscular (3 cases) or with expectant management. We obtained clinical resolution and undetectable hormone levels in seven patients and three underwent additional surgery. PMID- 1285268 TI - Human antibodies to dengue and yellow fever do not react in diagnostic assays for hepatitis C virus. AB - Hepatitis C virus (HCV) is a recently described causative agent of the great majority of post-transfusion non A-non B hepatitis and is classified within the Flaviviridae family. Due to a high prevalence of anti-HCV and other flaviviruses circulating in Brazil, such as dengue and yellow fever, we investigated the possibility of serological cross-reactivity between these viruses. Different panels of human sera positive for dengue type 1 (9 cases) and type 2 (7 cases) from 6 patients naturally infected with yellow fever and from 94 adults vaccinated against the 17D strain of yellow fever were tested against HCV antigens used in diagnostic assays. Two enzyme immunoassay systems were tested: one, an in-house test using recombinant antigens from core, NS3 and NS5 regions of the HCV genome (Research Foundation for Microbial Disease of Osaka University, Japan); and another, using synthetic peptides representing immunodominant epitopes of structural core and non-structural NS4 and NS5 HCV regions (INNOTEST HCV Ab, Innogenetics, Belgium). A line immunoassay (INNO-LIA HCV Ab, Innogenetics, Belgium) was used as a confirmatory test. In this, HCV antigens are coated as discrete lines on a nylon strip with plastic backing. Besides 4 control lines on each strip, a total of 6 HCV lines are present: line A consists of several NS4 epitopes, line B consists of several NS5 epitopes and lines C-F contain several core epitopes. This test not only confirms but differentiates antibodies to hepatitis C virus. No positive results were detected with these tests, indicating that hepatitis C infection can be evaluated by current assays in regions where flaviviruses are endemic. PMID- 1285269 TI - Cytomorphological and immunocytochemical evaluation of fine needle aspirates from high grade non-Hodgkin's lymphomas. AB - 1. Fine needle aspirates from ten patients with high-grade malignant non Hodgkin's lymphomas were analyzed by cytomorphology and immunocytochemistry. 2. The following morphologic diagnoses were made: lymphoblastic lymphoma (3 cases), Burkitt's lymphoma (3 cases), mixed small and large cell lymphomas with predominance of large cells (2 cases), and centroblastic lymphoma (2 cases). Immunocytochemistry showed a B-cell phenotype in five cases and a T-cell phenotype in four. One case of lymphoblastic lymphoma was negative for the T and B cell markers used. 3. The results of histological and immunohistochemical analyses performed on surgical biopsies from 8 patients confirmed the morphological diagnosis in all cases. Two cases of Burkitt's lymphoma were submitted only to cytological and immunological diagnosis. 4. The high diagnostic accuracy of combined cytomorphology and immunocytochemical assessment of fine needle aspirate samples validates the use of the technique in the diagnostic work up of high-grade non-Hodgkin's lymphomas. PMID- 1285271 TI - Double dens invaginatus of molarized maxillary central incisors, premolarization of maxillary lateral incisors, multituberculism of the mandibular incisors, canines and first premolar, and sensorineural hearing loss. AB - Molarization and premolarization of anterior teeth have never been reported before. Double dens invaginatus is an extremely rare condition. We describe an affected female who had developmental delay and congenital progressive sensorineural hearing loss. Double dens invaginatus of molarized maxillary central incisors and premolarized maxillary lateral incisors were present. In addition, multituberculated mandibular incisors, canines, and first premolar were observed. Histologically, tooth structure was unremarkable. Family history of dental abnormalities and hearing loss was denied. Clinical and radiographic examinations were those performed when the patient was 7 and 13 years old. The basic defect is postulated to be of mesenchymal origin. PMID- 1285270 TI - [Plasma levels of MHPG, HVA and total 5-HIAA in depression. Preliminary study]. AB - This study was aimed at assessing monoamine catabolites plasma levels in depressed patients and healthy volunteers. Plasma levels of 3-methoxy-4 hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) of 21 control subjects and 26 depressed patients (according to DSM III-R criteria) were measured at baseline (day 0) and day 4, day 7, day 30 of prescribed antidepressant treatment. The clinical assessment, at baseline as well as during treatment, used the Hamilton depression rating scale and the BPRS. Our data show the interest of these results in predicting response. The respondent patients showed a significant decrease in plasma MHPG level at J7, contrary to non-respondent patients. Moreover, a positive correlation between plasma levels of MHPG and HVA before any prescribed antidepressants was found only with respondent patients. The lack of correlation for non-respondent patients can suggest that the relationships between this monoamine systems should be disrupted in these patients. Significant relationships appear between clinical symptoms and plasma catabolites, allowing us to consider new physiopathological aspects of the depressive picture. The 3 monoamines seemed involved in sleep disorders. Perturbations of norepinephrine and serotonin metabolism could intervene in suicidal ideation and behaviour. Motor activity was associated with a modification in dopamine and serotonin metabolism. Moreover significant correlations were observed between items referring to thought content and monoamine plasma catabolites such as MHPG and blunted affect, 5-HIAA and obsessions, HVA and guilt feelings, devalorization and without hope items.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285272 TI - Autosomal recessive Silver-Russell syndrome. AB - Six children (5 male, 1 female) of normal first cousin Arab parents were found to have Silver-Russell syndrome. Manifestations included intrauterine and postnatal growth retardation, lateral asymmetry, relatively large head, small triangular face with prominent ears, clinodactyly of the fifth fingers, disproportionate toes, and normal psychomotor development. Intrafamilial variability was minimal. Parental consanguinity and affected siblings of both sexes strongly suggest autosomal recessive inheritance. Similar cases from literature are briefly reviewed. PMID- 1285273 TI - In vivo effects of OK-432, inosine pranobex and its salt components on macrophage subpopulations in spleen and peritoneum of mice during the primary humoral immune response. AB - Subsets of macrophages (BM 8-, la- and esterase-positive subtypes) in the spleen and the peritoneum of mice were affected differently by immunomodulators during the humoral immune response. I.p. application of inosine pranobex (INPX), as well as of its salt moiety (DIPPACBA) and its dimethylaminopropanol (DIP) and acetamidobenzoic acid (PACBA) components, increased the number of nonspecific esterase-bearing cells in the peritoneum on day 3. INPX and DIPPACBA stimulated the la+ macrophage on day 3, DIPPACBA the BM 8+ macrophage only on day 1 and DIP on day 5. In spleen, DIP and PACBA had marked effects on the la+ subset in addition to a marginal effect on the BM 8+ phenotype on day 1. DIPPACBA also influenced the BM 8+ macrophage slightly on day 1. In contrast, the microbial product OK-432 stimulated BM 8+ and la+ macrophages in spleen markedly on day 1, but only marginally on days 3 and 5. However, it exerted a strong effect on both subtypes in peritoneum on days 3 and 5. OK-432 was found to be without any influence on esterase-bearing macrophages. The results show that the heterogeneity of macrophages is not only represented by subset markers, but also by their susceptibility to immunomodulators in different organs and stages of the immune response. PMID- 1285274 TI - Food allergy as a cause of rhinitis and/or asthma. AB - We studied the histories of patients who had visited our Department during the last 5 years, presenting food allergy with exclusively respiratory symptoms (18.5%). We studied the correlation between IgE levels and the histamine release test and the type of food implicated. Seventy-seven percent of patients presented sensitization to one food, and 23% presented polysensitization. We found that foods such as snails and eggs have a strong predilection for the bronchial tree as the shock organ. High total IgE was found in 85.2% of patients. The histamine release test was positive in 66% of cases. We conclude that this is a highly sensitive method for the in vitro diagnosis of food allergy. PMID- 1285275 TI - Furosemide inhibits in vitro histamine release induced by antigens and anti-IgE. AB - We used 56 samples of heparinized blood of patients with asthma and/or allergic rhinitis, which were stimulated with Dermatophagoides pteronyssinus or gramineous pollen and anti-IgE in order to study the effect of furosemide on histamine release in basophils. At the same time, blood samples incubated in furosemide in different concentrations (2.5 microM to 1.49 mM) were also subjected to the same stimuli. Results showed a linear and dose-dependent inhibition of histamine release for antigens (r = 0.96; p < 0.01) and anti-IgE (r = 0.95; p < 0.05), reaching 95% at maximum inhibition. These results support the hypothesis that furosemide may act on mastocytes and basophils, thus inhibiting the release of histamine and other mediators. PMID- 1285276 TI - Analysis of gastrinomas by immunohistochemistry and in situ hybridization histochemistry. AB - Gastrinomas from 25 patients were examined by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISH). Most patients (84%) presented with the Zollinger-Ellison syndrome. Six had multiple endocrine neoplasia type I (MEN-I). Twelve patients (48%) had duodenal primaries and 11 of 12 of these had metastases to regional lymph nodes and/or liver in spite of the small sizes of the primary tumors (mean size of 0.9 cm). Five patients had pancreatic gastrinomas and eight patients had metastatic tumor in regional lymph nodes or liver at surgery but a primary was not found. IHC and ISH analyses showed that all cases were positive for gastrin protein and 24 of 25 (96%) expressed gastrin mRNA that was easily detected in formalin-fixed, paraffin-embedded tissue sections. Both benign and malignant tumors expressed alpha subunit of human chorionic gonadotropin protein (alpha-HCG). However, only malignant gastrinomas (29%) expressed adrenocorticotropic hormone protein or proopiomelanocortin (POMC) mRNA. ISH and Northern hybridization analysis revealed that chromogranin A mRNA was the most common member of the chromogranin/secretogranin (Cg/Sg) family which was expressed in both benign and malignant gastrinomas. These results indicate that duodenal gastrinomas are common in both sporadic and MEN-1-associated cases, and small duodenal primaries may be associated with extensive regional lymph node and liver metastases. Expression of ACTH/POMC protein and mRNA was consistently associated only with malignant gastrinomas while gastrin protein, gastrin mRNA and Cgs/Sgs mRNAs were readily detected in both benign and malignant gastrinomas. PMID- 1285277 TI - Localization of Mycobacterium avium-intracellulare within a skin lesion of bacillary angiomatosis in a patient with AIDS. AB - We report a 39-year-old man who had AIDS and who presented with an unusual cutaneous vascular lesion, which was clinically thought to be Kaposi's sarcoma. Histologically, the lesion was characterized by capillary proliferation and a mixed inflammatory infiltrate that included numerous histiocytes. The lesion was found to contain slender intracellular acid-fast bacilli, as well as plump extracellular Warthin-Starry-positive bacilli. The acid-fast bacilli were confirmed to be Mycobacterium avium-intracellulare by subsequent positive blood cultures for this organism. To further investigate the lesion, polymerase chain reaction DNA amplification and sequencing was performed, and the lesion was found to contain DNA sequences identical to those previously established for the agent of bacillary angiomatosis. The lesion is thought to represent a lesion of bacillary angiomatosis with secondary involvement by M. avium-intracellulare. PMID- 1285278 TI - [Ventricular extrasystole and coronary disease: to treat or not to treat?]. AB - The prognostic significance of ventricular premature beats (VPB) and their proper management are still a subject of controversy, particularly since during the last few years a number of publications have raised doubts as to the effectiveness and safety of antiarrhythmic drugs. An appropriate assessment of the VPB must consider: 1) electrocardiographic characteristics. 2) Associated symptoms. 3) Presence or absence of underlying disease, and 4) Ventricular function (VF). On this basis VPB may be classified as "Benign" (isolated; asymptomatic; mild or absent cardiopathy, and preserved VF); "Hazardous" (presence of complex VPB; with or without symptoms, and recognized organic heart disease), and "Malignant" (complex VPB and ventricular tachyarrhythmias; symptomatic cardiac disease, and compromised VF). Antiarrhythmic drugs are indicated for "Hazardous" and "Malignant" VPB. However, selection and efficacy must be documented by objective testing (Holter, stress, plasma levels). When utilized in well defined groups of patients, with reduction in the hourly number of VPB (more than 50-70%) and mainly of complex forms, there is clear benefit in terms of long-term survival, including coronary disease and congestive heart failure. PMID- 1285280 TI - Rat stem-cell factor induces splenocytes capable of regenerating the thymus. AB - Cytokine regulation of prethymic T-lymphoid progenitor-cell proliferation and/or differentiation has not been well-defined, although much is known of cytokine regulation of hemopoietic stem- and progenitor-cell development. Here we use a recently identified hemopoietic growth factor, stem-cell factor (SCF) (a form of the c-kit ligand), and a transplant model of thymocyte regeneration to assess the effect of SCF on the in vivo generation of prethymic, thymocyte progenitor-cell activity. We show that recombinant rat SCF (rrSCF164) administered to weanling rats selectively induces an increase in thymocyte progenitor activity in the spleens of treated rats as compared to rats treated with vehicle, polyethylene glycol (PEG)-conjugated rat albumin, or recombinant human granulocyte colony stimulating factor (rhG-CSF). These data demonstrate that administration of SCF in vivo affects extrathymic-origin thymocyte regenerating cells and may influence, directly or indirectly, early prethymic stages of T-cell lymphopoiesis in addition to its known effect on early stages of myelopoiesis and erythropoiesis. PMID- 1285279 TI - Studies on the extraction of DesPro(2)-Val15-Leu17-aprotinin from the culture broth of a recombinant Saccharomyces cerevisiae. AB - The application of an aqueous two-phase system is described for the extraction of DesPro(2)-Val15-Leu17-aprotinin from yeast culture supernatant, using native chymotrypsin as affinity ligand. The interaction is driven by hydrophobic forces and leads to the accumulation of the aprotinin-chymotrypsin complex in the salt rich (bottom) phase of a polyethyleglycol/salt system. The complex may be dissociated at low pH values. The separation of the recombinant aprotinin and the protease required chromatographic processes, which proved difficult to interface with the affinity extraction. PMID- 1285281 TI - Structure-function relations in schizophrenia: brain morphology and neuropsychology. PMID- 1285282 TI - [Urodynamic study of obstructive uropathy due to benign prostatic hyperplasia]. AB - Urodynamic examinations in patients with obstructive uropathy due to prostatic adenoma before and after prostatectomy were done over a 6-year-period (1981-1988) at the Department of Urology, Pula Medical Centre. In a comparative group of 30 healthy examinees and in 125 patients with obstructive uropathy as a result of benign prostatic hypertrophy, a maximal uroflowmetry and flow volume measurement were also performed. Control urodynamic studies were done 12 weeks after prostatectomy in 112 patients, and in 102 patients after 12 months. Preoperative and postoperative mean values of maximal uroflow were comparable. The aim of these urodynamic investigations is to estimate their value for a more complete and precise diagnosis of prostatism, and to determine, by urodynamic flow measurement before and after surgery, an outcome of prostatectomy in removal of prostatism symptoms and for urine flow improvement. Eighty-six patients underwent then open surgery, and 38 were operated transurethrally. The benign hypertrophy diagnosis was confirmed by histological analysis in all patients. PMID- 1285283 TI - Autoimmunity. AB - The immune system has evolved to protect an organism from the pathogens that invade it but the effector mechanisms involved in mediating this protection are potentially lethal to the host itself. Consequently it is essential that they are not elicited by the host's own tissues and, because biochemically self and non self are very similar, the immune system has had to develop an exquisite capability to distinguish relatively minor differences. There has been considerable progress recently in understanding how this discrimination is achieved although many questions remain. The problem is important in that the mechanisms that ensure self tolerance occasionally fail. The consequences of this failure are the autoimmune diseases, many of which afflict Man. This article reviews what is known about the way that the immune system normally avoids self reactivity and how breakdown in self tolerance can occur. PMID- 1285284 TI - [Patient rehabilitation after a palliative operation for cancer of the large intestine]. PMID- 1285285 TI - Changes in the nucleic acids and protein content of the ovaries in relation to a short and long photoperiod in a freshwater catfish Heteropneustes fossilis (BL). PMID- 1285286 TI - The effect of graded single oral doses of prostacyclin on the nucleic acid content of rat gastric mucosa. AB - Graded single oral doses of prostacyclin significantly enhance in dose-dependent manner the DNA and RNA content of rat gastric fundic mucosa, - resulting in a decreased RNA/DNA ratio. This latter phenomenon is convincing sign of new cell formation. In the antral region no significant changes could be encountered but the RNA content showed a tendency-like elevation, evoking an elevated RNA/DNA ratio, which corresponds to de novo protein synthesis. The diversity of the noted changes gives further evidence to the tenet the antral and the fundic gastric mucosa of the rat reacts differently toward external stimuli. PMID- 1285287 TI - [The dynamics of the reparative regeneration of the rat epidermis exposed to lysylproline]. AB - Under study was the spatial distribution of mitotic activity (MA) of the rat epidermis in the process of reparative regeneration of the skin for a distance of 6 mm aside from the wound margin, as well as the action of lysyl-proline (LP) on the process which is a product of natural decay of collagen. The wound was made by cutting a skin flap (0.5 x 3 cm) from the area of the back. A teflon ring was introduced through the incision in the cranial direction at a distance of 3 cm. Control animals were given 1 ml of the isotonic solution of sodium chloride injected in the hole of the ring, for experimental animals the solution additionally contained 20 mkg of LP. Healing of the wound in control and experimental animals had the features generally corresponding to the regularities established earlier. It was also found that mitotic activity was growing irregularly forming waves. During 11 days of observations these waves sometimes came nearer to the center of the wound, sometimes moved away. The influence of LP manifested itself in the waves of MA reaching the wound center 1 day earlier, and the approximation and divergence of the waves were smoother, MA was higher and epithelialization of the wound surface also came 1 day earlier. Since the contraction of the wound in experimental animals was also more rapid (activization from the 3rd day), a conclusion can be made of the stimulating influence of LP on the course of the reparative regeneration of the epidermis observed as long as 1.5 weeks after a single injection of LP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285288 TI - [The intermediate nerve system]. AB - A comparative-embryological study (223 fetuses of man, cat, dog, albino rat and mole) has established a similarity in the development and structure of the intermediate nerve in mammalia. The nerve under study represents a complex structural-functional system. Its afferent component includes a geniculate ganglion, a nucleus of the solitary tract, root, peripheral branches. A superior salivary nucleus, a root, pterygopalatine, submandibular, sublingual and auricular (in man) parasympathetic ganglia of the head, peripheral branches. The intermediate nerve fibers are included as additional sources in branches of other cranial nerves, vegetative ganglia and plexuses being spread on a considerable territory of the head. The intermediate nerve is an isolated anatomical structure and deserves being detached into a separate pair of cranial nerves. PMID- 1285289 TI - [The morphofunctional characteristics of the vascular bed of the lymph nodes]. AB - By means of silver nitrate impregnation and ATPase methods the distribution of all links of the lymph node vascular bed has been investigated. Structure of the blood capillary wall has been studied electron microscopically; they are defined as capillaries of the I type, that is having a continuous endothelial and basal layers and a small diameter. An essential amount of ribosomes is specific for blood capillary endothelium in the lymph nodes. A dendrite-like ramification of the portal veins is described, dichotomic--for the cerebral arteries, as well as the distribution of cortical arteries and arterioles. The postcapillary venules are found to localize around the lymphoid noduli and in the paracortical zone. Morphological bases for better exchange between blood and lymph are demonstrated in the cortex of the lymph node. Morphological signs of littoral cells of the lymphatic sinuses have been investigated and a conclusion is made on similarity in the structure of the lymphatic sinus wall and the wall of the lymphatic capillaries. Tight structural interrelations have been stated to exist between the wall of the lymph node blood vessels, its stroma and the wall of the lymphatic sinuses. PMID- 1285290 TI - [Flat preparations of the tunica intima of the major blood vessels (a review of new possibilities)]. PMID- 1285291 TI - [The cytoarchitectonic characteristics of field 17 of the occipital area of the human cerebral cortex in the right and left hemispheres]. PMID- 1285292 TI - [The topical organization of the nuclear projections of the amygdaloid body, the ventral tegmental field and the substantia nigra into the striopallidum of the cat]. AB - The work has generalized and compared results of studying the topical organization of projections of the amygdaloid body, ventral tegmental area and substantia nigra in the extrapyramidal system of the cat's brain. Methods of retrograde axon transport of horseradish peroxidase and fluochrome were used. In the basal ganglia the limbic and motor areas were found with prevailing projections from structures belonging to the limbic system or from the formations bearing a relation to motor activity. Parallel with this, in considerable areas of the basal ganglia there occur overlapping projection fields of the axons belonging to neurons of the both structures. This fact as well as the widely represented in the striopallidal system divergence of axons of neurons belonging to many structures are discussed in association with the hypothesis of the interaction of the limbic and motor systems in the basal ganglia. General features found in the topical organization of projections from the structures under investigation onto the striopallidum nuclei and specific features for each of the nuclei are discussed in connection with similar and different manifestations of behavioral reactions or clinical disturbances in neurological diseases. PMID- 1285294 TI - [The symbolism of food]. PMID- 1285293 TI - Platelet-derived growth factor gene expression in the kidney of malignant hypertension. AB - To examine the pathogenetic role of platelet-derived growth factor (PDGF) in hypertensive kidney damage, we studied the gene expression of PDGF A-chain and B chain in an animal model of malignant hypertension. Experimental malignant hypertension induced by unilateral nephrectomy combined with deoxycorticosterone and salt loading in the spontaneously hypertensive rat resulted in severely elevated blood pressure and renal histological damage, characterized by necrotizing vasculitis. Using reverse transcription-polymerase chain reaction analysis followed by Southern blot analysis, we observed that PDGF B-chain gene expression was increased in the kidney of experimental malignant hypertension and was correlated with the severity of glomerular damage, while PDGF A-chain gene expression was unaffected. Antihypertensive treatment with manidipine reduced glomerular damage and a decreased gene expression of PDGF B-chain. These results suggest that PDGF B-chain may have a role in mediating hypertensive kidney damage. PMID- 1285295 TI - Microcalorimetric evaluation of the effects of methotrexate and 6-thioguanine on sensitive T-lymphoma cells and on a methotrexate-resistant subline. AB - Isothermal microcalorimetry was used in order to continuously monitor and quantitatively assess the action of two antineoplastic drugs, methotrexate (MTX) and 6-thioguanine (6-TG), on a human T-lymphoma cell line, CCRF-CEM. The results with MTX were compared with data from experiments with a MTX-resistant subline, CEM/MTX. The slope of the power-time curve after drug injection relative to that obtained during unperturbed growth, was used to construct dose-response curves. The normal cell line was characterized by a D50 value (i.e., the dose producing half the maximal response) of 0.05 microM for MTX and 0.38 microM for 6-TG. For the MTX-resistant subline the D50 value was 8 microM of MTX. Comparisons of the continuous power-time curves showed the inhibitory effect of 6-TG to be faster than that of MTX. PMID- 1285296 TI - The lateral separation of contacts on erythrocytes agglutinated by polylysine. AB - The form of contact seam (whether a continuous parallel seam or membranes in spatially periodic contact) has been characterized for normal and for neuraminidase pretreated human erythrocytes following adhesion in solutions of polylysine in the molecular mass range 10-225 kDa at concentrations from 0.5 to 1.0 mg/mL. The adhesion contact seam was spatially periodic for all normal control cells in polylysine. The lateral separation of contacts decreased from 1.6 to 0.8 microns as the concentration of 225 kDa polylysine was increased threefold from the adhesion threshold value. The separation distance did not change further even at high polymer concentrations that increased the electrophoretic velocity to positive values over twice the modulus of the velocity of control cells. The probability of cell adhesion decreased at these high polymer concentrations. The lateral contact separation increased and cell adhesion decreased for cells pretreated with neuraminidase. Cell adhesion did not occur when neuraminidase reduced the cell electrophoretic velocity modulus by 30%. Following neuraminidase pretreatments that allowed a small amount of adhesion, the cell contact seam was continuous rather than spatially periodic. The results show that a procedure that increases (e.g., polymer concentration increase) or decreases (e.g., enzyme removal of polycation crosslinking site) attraction leads to shorter (to a limiting value) or longer lateral contact separation, respectively. PMID- 1285297 TI - Influence of glutaraldehyde fixation of cells adherent to solid substrata on their detachment during exposure to shear stress. AB - In order to determine the response of fixed and nonfixed cells adherent to a solid substratum to shear stress, human fibroblasts were allowed to adhere and spread on either hydrophilic glass or hydrophobic Fluoroethylene-propylene (FEP Teflon) and fixed with glutaraldehyde. Then, the cells were exposed to an incrementally loaded shear stress in a parallel plate flow chamber up to shear stresses of about 500 dynes/cm2, followed by exposure to a liquid-air interface passage. The cellular detachment was compared with the one of nonfixed cells. In case of fixed cells, 50% of the adhering cells detached from FEP-Teflon at a shear stress of 350 dynes/cm2, whereas 50% of the adhering, nonfixed cells detached already at a shear stress of 20 dynes/cm2. No fixed cells detached from glass for shear stresses up to at least 500 dynes/cm2. More than 50% of the nonfixed cells were detached from glass at a shear stress of 350 dynes/cm2. Furthermore, the shape and morphology of fixed cells did not change during the incrementally loaded flow, in contrast to the ones of nonfixed cells, which clearly rounded up prior to detachment. PMID- 1285298 TI - Kinetics of interleukin-2 induced changes in rigidity of human natural killer cells. AB - The success of adoptive immunotherapy is dependent in part on the successful delivery of effector cells to the tumor and the expression of cellular activities, such as adhesion, extravasation, and cytotoxic activity of the effector cells in the tumor. The structural rigidity of the effector cell is an important determinant of these functions. The present study was designed to quantify the changes in cellular rigidity and cytotoxic activity of human natural killer (NK) cells in the presence or absence of interleukin-2 (IL-2). Micropipet aspiration was used to measure the resistance of NK cells to an imposed external deformation. Homogeneous suspensions of NK cells were activated with 1000 U/mL of recombinant IL-2 in vitro and tested for cellular rigidity from 0 to 96 h post stimulation. The IL-2 activated cells increased their rigidity within 24 h and maintained it at this level for 96 h. Prolonged incubation of cells in IL-2 (14 d) resulted in a consistently high rigidity, which was further increased on starvation of the cells from IL-2. The increased rigidity of these cells was maintained throughout 96 h of IL-2 deprivation, although significant relaxation of rigidity was observed between 48 and 96 h. The relaxation of rigidity was associated with an increase in the number of nonviable cells. Reintroduction of IL-2 for 24 h to a culture of NK cells depleted of IL-2 for 48 h did not restore the cells to the pre-depletion level of rigidity. Cytotoxic activity of the activated NK cells following removal of IL-2 decreased to about 60% of the control activity within 24 h and continued through 72 h post-deprivation. These findings suggest that the initial activation of human NK cells by IL-2 will produce a relatively rapid increase in rigidity that may cause entrapment of these cells in small capillaries in vivo and that removal of IL-2 will produce an additional increase in rigidity, which is associated with decreased functional activity. PMID- 1285300 TI - Development of inhibitors of reverse transcriptase and protease as therapeutics against HIV infection. PMID- 1285299 TI - Morphology of cell-substratum adhesion. Influence of receptor heterogeneity and nonspecific forces. AB - Many cell types modulate growth, differentiation, and motility through changes in cell substrate adhesion, including regulation of focal contact formation. Clustering of cell surface adhesion receptors is an essential early step in the development of focal contacts, and thus may influence cell physiology. In this paper, we present a theoretical framework to examine how cell surface chemistry affects receptor clustering. Our one-dimensional tape-peeling model couples the equations of mechanical equilibrium for a cell membrane with kinetic receptor ligand binding relations. We considered two distinct model scenarios: Adhesion mediated by multiple receptor-ligand interactions of different length and specific binding of a single receptor type occurs in the presence of van der Waals attraction and nonspecific repulsion. In each case, nonuniform (wave-like) membrane morphologies are observed in certain parameter ranges that support the clustering of adhesion receptors. The formation of these morphologies is described in terms of a balance of membrane stresses; when cell-surface potential as a function of separation distance is symmetric between two potential energy minima, nonuniform morphologies are obtained. Increases in the chemical binding energy between receptor and ligand (e.g., increases in ligand density) or decreases in the membrane rigidity result in smaller wavelengths for nonuniform interfaces. Additionally, we show wave-like geometries appear only when the mechanical compliance of receptor-ligand bonds is within an intermediate range, and examine how the mobility of "repellers"--glycocalyx molecules that exert a nonspecific repulsive force--influences membrane morphology. We find fully mobile repellers always redistribute to prevent nonuniform morphologies. PMID- 1285301 TI - Inhibitors of HIV-1 reverse transcriptase and fidelity of in vitro DNA replication. AB - Mechanisms of the effects of the dTTP analogues 3'-azido-3'-deoxythymidine 5' triphosphate (AZTTP) and 3'-amino-3'-deoxythymidine 5'-triphosphate (NH2 TTP) upon the HIV-1 reverse transcriptase (RT) are discussed. These compounds block the RT in vitro and do so by different kinetic mechanisms. Infidelity of replication is a hallmark of the HIV-1 RT, and replication errors by the enzyme on RNA and DNA templates are discussed. The enzyme's infidelity has ramifications for inhibition: On the one hand, the propensity to produce mutations enhances the ability of the virus to escape inhibitors whereas on the other hand, the infidelity of the reverse transcriptase may allow the development of imaginative inhibitor strategies. PMID- 1285302 TI - Specific HIV-1 reverse transcriptase inhibitors. PMID- 1285303 TI - Emergence of mutant HIV reverse transcriptase conferring resistance to AZT. PMID- 1285304 TI - Inhibitors of HIV-1 protease. AB - The human immunodeficiency virus (HIV), the etiological agent for the acquired immune deficiency syndrome (AIDS), is a retrovirus which makes use of a virally encoded aspartic protease to perform specific proteolytic processing of two of its gene products in order to form active enzymes and structural proteins within the mature virion. Accordingly, specific, exogenous inhibition of the HIV-1 protease is thought to be a viable approach for the development of novel therapeutics for the treatment of AIDS. Indeed, this hypothesis has been validated in virally-infected cell culture with synthetic inhibitors of HIV-1 protease. This chapter reviews the current status of the development of inhibitors of this enzyme. PMID- 1285305 TI - Reverse transcriptase--a general discussion. PMID- 1285306 TI - Correlations between the in vitro and in vivo activity of anti-HIV agents: implications for future drug development. AB - Some 10 years after the first recognition of acquired immunodeficiency syndrome (AIDS) as a new syndrome, we have identified a number of molecular targets to interrupt the replicative cycle of human immunodeficiency virus (HIV), the causative agent. A number of dideoxynucleosides have been identified as having anti-HIV activity in vitro, and several of these have been found to have clinical activity in patients. In contrast, while a number of agents have been found to block viral binding to the target cell in vitro, these agents have generally not shown clear-cut evidence of clinical activity. Agents which act at a variety of steps in the HIV replicative cycle are now under development, and it is likely that we will have an increased armamentarium to fight this disease in the near future. PMID- 1285307 TI - [Dissection of the ascending aorta (type A): diagnostic aspects, surgical treatment and long-term follow-up]. AB - Aortic replacement is the treatment of choice and improves the natural history of dissections involving the ascending aorta. Forty patients (23 male), aged 49.4 years, have been operated at the hospital Clinico de la Universidad Catolica. Twenty six presented with acute dissections. Angiography conformed the dissection in 63.3% and computed axial tomography in 84.6% of patients; lately, transesophageal echocardiography has become the most sensitive diagnostic method. Twenty three patients (57.5%) were subjected to emergency operations and 17 to semielective procedures. In 24 patients (60%) ascending aorta was replaced and in 16 a composite graft was used. Operative mortality was 27.5%. Univariate analysis showed that the period in which the operation was performed and the presence of limb ischemia were the only independent predictors of operative mortality. Long term follow up was achieved in 26 patients (89.6%). Actuarial 5 year survival without considering operative mortality was 87.9%. It is concluded that patients with acute dissections involving the ascending aorta should be operated as soon as the imaging diagnosis is complete and, since this is a palliative procedure, a close follow up is required for early detection of complications. PMID- 1285309 TI - Immunohistochemical analysis of GH-producing adenomas--with special emphasis on plurihormonality of individual tumor cells by double staining. AB - Forty-four human growth hormone (GH)-producing adenomas were investigated immunohistochemically for the concomitant localization of GH, prolactin (PRL), and glycoprotein hormone alpha subunit. Immunoreactivity for GH, PRL, and the alpha subunit was found in 44, 37, and 36 cases, respectively. By double immunohistochemical staining, 24 of 27 cases showed colocalization of GH and alpha subunit, with the numbers of tumor cells showing double staining varying from case to case. The colocalization of GH and alpha subunit was noted in some normal pituitary cells. In adenoma cells, the colocalization of GH and PRL, and PRL and alpha subunit, was observed in 9 and 12 cases, respectively. The normal pituitary gland showed only occasional colocalization of GH and PRL, or PRL and alpha subunit. We found that GH-producing adenomas are plurihormonal at the individual tumor cell level, with coexpression of GH-alpha subunit, GH-PRL, and PRL-alpha subunit. The colocalization of GH and alpha subunit may be an expression of a subpopulation of normal anterior pituitary cells (with GH-alpha subunit coexpression), but the more frequent coexpression of GH-PRL may be pathological, accompanying tumorigenesis of the anterior pituitary cells, in which a pituitary-specific transcriptional factor, pit-1, may play a role. PMID- 1285308 TI - CD4 subsets in IgA nephropathy. AB - CD45RA+ (2H4+) and CD45RA-(CD29, 4B4+) antigenic expressions, recognized as a suppressor inducer and a helper inducer, respectively, on CD4+ and T alpha 4+ cells (Fc alpha receptor bearing CD4 T cells) were measured by three color flow cytometry in patients with IgA nephropathy (IgAN). The 4B4+ subsets of CD4 and T alpha 4 T cells were increased significantly in the patient group compared with the control group. The level of the 2H4+ subset did not differ between the two groups. No significant correlation was observed between the increase in the 4B4+ subset and disease severity, as estimated by measuring the proteinuria, levels of serum creatinine and immunoglobulins (Igs) or renal tissue damage. It was concluded that 4B4+ CD4+ and 4B4+ T alpha 4+ subsets might be involved in the mechanism of immunopathogenesis of IgA nephropathy. PMID- 1285311 TI - [Specificity of psychomotor therapy]. PMID- 1285310 TI - Rheumatoid factors from patients with rheumatoid arthritis react with beta 2 microglobulin. PMID- 1285312 TI - [Kurt Goldstein: from aphasia to linguistics]. AB - The authors try to take into account Kurt Goldstein's contribution on the subject of aphasia. They introduce the significance of the phenomenological approach of the language leading them toward the structuralist theme. PMID- 1285314 TI - Plasmodium falciparum CS protein--prime malaria vaccine candidate: definition of the human CTL domain and analysis of its variation. AB - Studies in mice have shown that immunity to malaria sporozoites is mediated primarily by cytotoxic T lymphocytes (CTL) specific for epitopes within the circumsporozoite (CS) protein. Humans, however, had never been shown to generate CTL against any malaria or other parasite protein. The design of a sub-unit vaccine for humans relies on the epitopes recognized by CTL being identified and polymorphisms therein being defined. We have developed a novel technique using an entire series of overlapping synthetic peptides to define the epitopes of the Plasmodium falciparum CS protein recognized by human CTL and have analyzed the sequence variation of the protein with respect to the identified CTL epitopic domain. We have demonstrated that some humans can indeed generate CTL against the P. falciparum CS protein. Furthermore, the extent of variation observed for the CTL recognition domain is finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways can be found to increase immune responsiveness, then a vaccine designed to stimulate CS protein-specific CTL activity may prevent malaria. PMID- 1285313 TI - Calcium permeability and modulation of nicotinic acetylcholine receptor-channels in rat parasympathetic neurons. AB - Neuronal nicotinic acetylcholine (ACh)-activated currents in rat parasympathetic ganglion cells were examined using whole-cell and single-channel patch clamp recording techniques. The whole-cell current-voltage (I-V) relationship exhibited strong inward rectification and a reversal (zero current) potential of -3.9 mV in nearly symmetrical Na+ solutions (external 140 mM Na+/internal 160 mM Na+). Isosmotic replacement of extracellular Na+ with either Ca2+ or Mg2+ yielded the permeability (Px/PNa) sequence Mg2+ (1.1) > Na+ (1.0) > Ca2+ (0.65). Whole-cell ACh-induced current amplitude decreased as [Ca2+]0 was raised from 2.5 mM to 20 mM, and remained constant at higher [Ca2+]0. Unitary ACh-activated currents recorded in excised outside-out patches had conductances ranging from 15-35 pS with at least three distinct conductance levels (33 pS, 26 pS, 19 pS) observed in most patches. The neuronal nicotinic ACh receptor-channel had a slope conductance of 30 pS in Na+ external solution, which decreased to 20 pS in isotonic Ca2+ and was unchanged by isosmotic replacement of Na+ with Mg2+. ACh-activated single channel currents had an apparent mean open time (tau 0) of 1.15 +/- 0.16 ms and a mean burst length (tau b) of 6.83 +/- 1.76 ms at -60 mV in Na+ external solution. Ca(2+)-free external solutions, or raising [Ca2+]0 to 50-100 mM decreased both the tau 0 and tau b of the nAChR channel. Varying [Ca2+]0 produced a marked decrease in NP0, while substitution of Mg2+ for Na+ increased NP0. These data suggest that activation of the neuronal nAChR channel permits a substantial Ca2+ influx which may modulate Ca(2+)-dependent ion channels and second messenger pathways to affect neuronal excitability in parasympathetic ganglia. PMID- 1285315 TI - Molecular mechanisms and biological importance of Plasmodium falciparum erythrocyte rosetting. AB - Rosetting, i.e. the spontaneous binding of uninfected to malaria infected erythrocytes and endothelial cytoadherence may hinder the blood flow and lead to severe Plasmodium falciparum malaria. Falciparum isolates obtained from unconscious patients all form rosettes and/or express a significantly higher mean rosetting rate than isolates from patients with uncomplicated malaria. Furthermore, sera of patients with cerebral malaria are devoid of anti-rosetting activity while sera from patients with mild disease carry high levels of anti rosetting antibodies. The presence of anti-rosetting antibodies also seems important for the efficient interaction of rosetting infected rbc and leukocytes. Two parasite derived rosetting ligands of Mr 22K and Mr 28K named "rosettins", have been found on the surface of rosetting infected erythrocytes. CD36 has in at least some strains of parasites been found to function as a rosetting receptor on the uninfected erythrocyte. Heparin disrupts rosettes of P. falciparum in vitro and inhibits the sequestration of rosetting cells ex vivo. In conclusion, rosetting seems a crucial factor in the development of cerebral malaria and treatment of patients with anti-rosetting substances might become an effective adjunct in the treatment of severe malaria. PMID- 1285316 TI - Epitope recognition in histone H1 by SLE autoantibodies in the presence of a DNA ligand. AB - To investigate the specificity of anti H1 antibodies peptides from the N- and C domain of H1 and the synthetic oligonucleotide (AT)6 were complexed. Circular dichroism (CD) spectroscopy indicated that the free peptides H1(1-16), H1(204 218) and C(121-210) in low salt buffer assume a random structure but become helical when bound to the oligonucleotide. The structured and unstructured H1 fragments were then analyzed by enzyme linked immunosorbent assay (ELISA) with anti-H1 antibodies in sera from patients with systemic lupus erythematosis (SLE) and with the monoclonal anti-H1 antibody MRA-12 derived from MLR lpr/lpr autoimmune mice. Binding of these antibodies to H1(204-218) and C was inhibited to a level of 50% when these H1 peptides were complexed with (AT)6. When the same antibody was tested with H1 fragment GC(34-210), attachment to oligonucleotide (AT)6 did not influence antibody binding. Competition studies with liquid phase GC and C antigen against solid phase GC and C indicated that liquid phase GC was more efficient in displacing antibody binding reactivity than liquid phase C. The displacement effect of both liquid phase antigens was greatest against solid phase C. We conclude that anti-H1 autoantibodies are directed against an epitope located near the junction of the G- and C-domain which is exposed and not masked when H1 is bound to DNA. PMID- 1285317 TI - Levels of CD5+ B cells are not increased in probands or relatives in a family study of primary Sjogren's syndrome. AB - Levels of CD5+ B lymphocytes were assayed in a large family study of Primary Sjogren's syndrome. There was no significant difference in CD5 expression by index cases or their relatives when compared to controls. No association between CD5 expression, serological abnormalities or HLA haplotype was found and, furthermore, no evidence of linkage with HLA was observed. There was, however, variation in the expression of CD5+ B cells between the families. Levels in spouses were lower and reached statistical significance. The role for genetic and environmental factors influencing CD5 expression is discussed. Any genetic influence does not appear to involve the HLA region or genes in linkage disequilibrium. PMID- 1285318 TI - Autoantigens in thyroid and islet autoimmunity: similarities and differences. PMID- 1285319 TI - Analysis of hemoglobin gamma chain in patients with Cooley's anemia in Taiwan. AB - The beta-like globin gene cluster, consisting of five genes and a pseudogene, is located on chromosome 11 and is arranged in the order 5'-epsilon-G gamma-A gamma phi beta-delta-beta-3'. With the fast and sensitive method of high-performance liquid chromatography (HPLC) in the gradient mobile system, we studied the G gamma values of fetal hemoglobin in 34 patients with Cooley's anemia, 100 normal adults and 100 newborns. There were 84 newborns with a mean G gamma value of 67.41 +/- 2.37%, 15 newborns with a G gamma value of 83.45 +/- 1.92% and one newborn with a G gamma value of 100%. Because the medium value of 67.41% and 100% is near the value of 83.45%, we speculate that there are different g gene genotypes; that is, the group with a G gamma value of 100% has a genotype of G gamma-G gamma/G gamma-G gamma, the group with a G gamma value of 83.45% has a genotype of G gamma-G gamma/G gamma-A gamma, and the group with a G gamma value of 67.41% has a genotype of G gamma-A gamma/G gamma-A gamma. The G gamma value for normal adults was 41.84 +/- 20.91%. While the G gamma values for patients with Cooley's anemia were divided into two groups, 56.23 +/- 6.55% and 80.60 +/- 3.05%. There was no case having a G gamma value of 100%. Our results suggest that the expression of the gamma gene in Cooley's anemia is similar to that of the newborns. PMID- 1285320 TI - Effect of dexamethasone, dimethylsulfoxide and sodium butyrate on a human hepatoma cell line PLC/PRF/5. AB - The effects of agents which are known to be differentiation inducers on a human hepatoma cell line PLC/PRF/5 were investigated. Dexamethasone (DEX), sodium butyrate (SB) or dimethylsulfoxide (DMSO) were examined. They all reduced cell proliferation but differ from each other in effect on the secretion of alphafetoprotein (AFP) and hepatitis B surface antigen (HBsAg), changes in morphology and RNA transcription. SB changed the cell from polygonal into a fibroblast-like type and decreased AFP secretion. DMSO decreased the cell size and changed AFP secretion in the same manner as SB. DEX changed the cell into a larger size, as well as increased AFP secretion. HBsAg secretion and also HB virus DNA transcription was enhanced by 3 agents. AFP and myc gene transcriptions were reduced by SB but DMSO reduced only AFP. Albumin gene transcription was enhanced by SB and DEX. These results indicate that the decrease of PLC/PRF/5 proliferation is induced through different mechanisms by these 3 agents. PMID- 1285322 TI - Tumor targeting with monoclonal antibodies. Advances in the applications of monoclonal antibodies in clinical oncology. May 4-6, 1992, Porto Carras, Greece. Proceedings. PMID- 1285321 TI - Expression of a Chlamydia anticarbohydrate single-chain antibody as a maltose binding fusion protein. AB - A single-chain antibody fragment has been constructed for an antibody that binds to the Chlamydia specific carbohydrate structure of the lipopolysaccharide. Single-chain protein was expressed and secreted into the periplasmic space of E. coli as a fusion protein with the maltose binding protein. The fusion protein was purified in one step by virtue of its ability to bind to maltose. In a sandwich ELISA, the eluted protein bound Chlamydia lipopolysaccharide, which demonstrates that the single-chain protein domain will function as part of a fusion protein. The expression of maltose binding fusion proteins into the periplasmic space could be used for production of other single-chain antibodies or protein fragments requiring appropriate folding and disulfide bond formation. PMID- 1285323 TI - Human immune response to monoclonal antibody-enzyme conjugates in ADEPT pilot clinical trial. AB - The human immune response to monoclonal antibody-enzyme conjugates has been studied in patients included in the pilot clinical trial of ADEPT. Each patient received murine monoclonal anti-CEA antibody fragments (A5B7-F(ab')2, conjugated to bacterial enzyme, carboxypeptidase G2 (CPG2) followed by a galactosylated monoclonal anti-CPG2 antibody (SB43), 36-48 h after the conjugate. Some patients were also given a dose of 131I-labeled conjugate (4-8 mg, 7-15 mCi) for blood clearance and gamma camera image studies. All patients studied developed human antimouse antibodies (HAMA) and anti-CPG2 antibodies within 10 d after a single course of treatment with the conjugate. In most cases, IgM response was detected at 7 d after the conjugate followed by the IgG response 14 d later. In one patient, HAMA and anti-CPG2 antibodies of the IgG type could still be detected at 10 mo after treatment. Anti-CPG2 antibodies in serum of one patient were found to inhibit CPG2 activity in vitro. Generation of neutralizing antibodies limits the use of repeat cycles of ADEPT in patients. Use of immunosuppressive agents may allow a useful time window for several ADEPT cycle treatments by delaying the appearance of HAMA and anti-CPG2 antibodies. Patients given cyclosporin A before and during ADEPT are currently being studied for HAMA and anti-CPG2 response. PMID- 1285325 TI - Immunotoxins to human small-cell lung cancer. AB - Ricin A chain ITs directed against a variety of the common cell-surface antigens associated with SCLC exerted selective toxic effects on SCLC cell lines. The potency of the cytotoxic effects matched or exceeded that previously reported for ricin A chain ITs directed against identical or similar antigens on other types of carcinoma, suggesting that SCLC may be uniquely sensitive to this type of IT. PMID- 1285324 TI - Rational immunotherapy with ribonuclease chimeras. An approach toward humanizing immunotoxins. AB - Members of the pancreatic ribonuclease (RNase) family have diverse activities toward RNA that could cause them to function during host defense and physiological cell death pathways. This activity could be harnessed by coupling RNases to cell binding ligands for the purpose of engineering them into cell-type specific cytotoxins. Therefore, the cytotoxic potential of RNase was explored by linking bovine pancreatic ribonuclease A via a disulfide bond to human transferrin or antibodies to the transferrin receptor. The RNase hybrid proteins were cytotoxic to K562 human erythroleukemia cells in vitro with an IC50 around 10(-7) M, whereas > 10(-4) M of native RNase was required to inhibit protein synthesis. Cytotoxicity required both components of the conjugate since excess transferrin or ribonuclease inhibitors added to the medium protected the cells from the transferrin-RNase toxicity. Importantly, the RNase conjugates were found to have potent antitumor effects in vivo. Chimeric RNase fusion proteins were also developed. F(ab')2-like antibody-enzyme fusions were prepared by linking the gene for human RNase to a chimeric antitransferrin receptor heavy chain gene. The antibody enzyme fusion gene was introduced into a transfectoma that secreted the chimeric light chain of the same antibody, and cell lines were cloned that synthesized and secreted the antibody-enzyme fusion protein of the expected size at a concentration of 1-5 ng/mL. Culture supernatants from clones secreting the fusion protein caused inhibition of growth and protein synthesis toward K562 cells that express the human transferrin receptor but not toward a nonhuman derived cell line. Since human ribonucleases coupled to antibodies also exhibited receptor mediated toxicities, a new approach to selective cell killing is provided. This may allow the development of new therapeutics for cancer treatment that exhibit less systemic toxicity and, importantly, less immunogenicity than the currently employed ligand-toxin conjugates. PMID- 1285326 TI - Optimum combination of targeted 131I therapy and total-body irradiation for treatment of disseminated tumors of differing radiosensitivity. AB - 131I is the radionuclide most commonly used in biologically targeted radiotherapy at the present time. Microdosimetric analysis has shown that microtumors whose diameters are less than the beta-particle maximum range absorb radiation energy inefficiently from targeted radionuclides. Micrometastases of diameters < 1 mm are likely to be spared if targeted 131I is used as a single modality. Because of this, combined modality therapy incorporating targeted 131I, external beam total body irradiation (TBI), and bone marrow rescue has been proposed. In this study, the minimum necessary TBI component is shown to depend on the radiosensitivity of the tumor cells. The analysis shows that the TBI component, to achieve radiocurability, increases directly with tumor radioresistance. For the most radiosensitive tumors, a whole-body TBI treatment dose 2 x 2 Gy is calculated to be obligatory, whereas practical arguments exist in favor of higher doses. For more radioresistant tumors, the analysis implies that a TBI treatment delivery of 5 x 2 Gy is obligatory. In all situations, external beam TBI appears to be an essential factor in providing reasonable probability of cure of disseminated malignant disease. Reasonable prospects of tumor cure by combination strategies incorporating 131I exist for the more radiosensitive tumor types (e.g., neuroblastoma, lymphoma, leukemia, myeloma, seminoma), but more resistant tumors are unlikely to be curable at present. Superior targeting agents, and the possible use of panels of different radionuclides, may be necessary to achieve high cure probabilities for less radiosensitive tumor types. PMID- 1285327 TI - The clinical significance of HAMA in patients treated with mouse monoclonal antibodies. AB - Twenty-four patients were analyzed for the development of HAMA (human antimouse antibodies) after being treated with repeated doses (200-500 mg) of the mouse monoclonal antibody (MAb) 17-1A. All patients developed anti-17-1A IgG antibodies, and most of them also developed IgM antibodies. In only two patients could immune complexes be demonstrated. Allergic reactions were rare (1.9%). In an extended study, a further 19 patient were analyzed for an idiotypic response. Forty-one out of 43 patients developed antiidiotypic antibodies (ab2), and 20 of these also anti-anti-idiotypic antibodies (ab3). Ab3+ patients responded significantly better (p = 0.01) and survived longer (p < 0.001) compared to ab3- patients. In this study, we showed that MAb 17-1A could be repeatedly given on a safe basis. The development of high titers of HAMA did not cause significant clinical problems when further repeated infusions of MAb 17-1A were given. The development of an idiotypic response also indicate that the induction of HAMA might be beneficial and not harmful to the patient. PMID- 1285328 TI - The p53 tumor suppressor gene. A preliminary clinical study in breast cancer patients. AB - p53 was originally considered to be a nuclear oncogene, but several convergent lines of research have indicated that the wild-type gene functions as a tumor suppressor gene negatively regulating the cell cycle. Mutations in the p53 gene have been detected in many tumor types and seem to be the most common genetic alterations in human cancer. In this preliminary study, sera of 92 patients (pts) with breast disease were analyzed for the presence of the mutant p53 protein (mp53) with a selective immunoenzyme assay employing a monoclonal antibody (PAb 240) specific for the majority of mammalian m p53 but not for the wild-type protein. Of the 10 patients with benign breast disease, only two (20%) showed detectable m p53 levels in the serum. In the breast cancer group, sera from 7 of the 30 pts (23%) without lymph node involvement were positive for m p53, as were 7 out of the 45 pts (15%) with metastatic lymph nodes and 1 out of the 7 pts (14%) with disseminated disease. The specificity of m p53 assay evaluated in 20 healthy controls was 100%. These preliminary results showed that serum positivity for m p53 is not related to breast disease extension. Further studies to assess the utility of m p53 as a possible prognosis factor in breast cancer are currently in progress. PMID- 1285329 TI - Use of the multipin peptide synthesis technique for the generation of antipeptide sera. AB - The multipin peptide synthesis technique has been used to map antigenic sites of proteins (1,2). Antibodies raised to the whole protein are screened on pin synthesized overlapping octapeptides homologous with the protein of interest, and the peptides that bind antibodies clearly identify the epitopes. What is described in this study is a method using pin-synthesized peptides to generate specific antibodies to many peptides. Cleavable linkers have been developed (3) that, used together with the multipin peptide synthesis technique, allow the synthesis and cleavage of many thousands of peptides into aqueous solutions at physiological pH. This technique is useful for assays requiring peptides in solution, e.g., mapping of T-cell determinants. A technique has been developed for the cleavage of many peptides from pins and simultaneous coupling to immunogenic carriers (4). The conjugates produced are suitable for the generation of antipeptide antibodies. This procedure is illustrated using several 15 amino acid long peptides (15-mers), homologous with the sequence of a model antigen, myohemerythrin (MHr). The resulting antipeptide sera generated were tested by ELISA for titer and specificity on pin-synthesized peptides and beta-amide peptides and the protein antigen coated to microtiter plates. PMID- 1285330 TI - Phase I imaging study of Hodgkin's disease and non-Hodgkin's lymphomas with radiolabeled antibody to eosinophil peroxidase. PMID- 1285331 TI - c-myc coded oncoprotein for immunotargeting. Oropharyngeal and other tumors at S.N. Medical College, Agra, India. PMID- 1285332 TI - Regulated secretion and purification of recombinant antibodies in E. coli. AB - A plasmid for optimized protein expression of recombinant Fv antibodies (pOPE) in E. coli was used to express the variable domains of the murine monoclonal antibody HD39 specific for the human B-cell surface antigen CD22. The production of Fv antibodies by pOPE can be regulated over a wide range by varying the IPTG concentration. Antibodies that can discriminate between secreted and nonsecreted Fv antibody fragments were used to show that secretion is the limiting step for the production of functional Fv antibodies. IPTG concentrations above 20 microM increased the total antibody production, but did not yield larger amounts of secreted Fv antibodies. The addition of five histidines to the C terminus facilitates an easy single-step enrichment procedure based on immobilized metal affinity chromatography. PMID- 1285333 TI - Recombinant human monoclonal antibodies. Basic principles of the immune system transferred to E. coli. AB - To produce human monoclonal antibodies in bacteria, a gene repertoire of IgM variable regions was isolated from human peripheral B lymphocytes by the polymerase chain reaction. Alternatively, synthetic antibody genes with random hypervariable regions are being generated that may provide libraries of even higher complexity. For the selection of specific monoclonal antibodies from these libraries, we have developed two E. coli vector systems that facilitate the surface display of an antibody physically linked to its own gene. The phagemid pSEX encodes a fusion protein of an antigen binding domain (Fv-antibody) with the docking protein (pIII) of filamentous phages. Specific antibody genes can therefore be enriched by antigen affinity chromatography. The plasmid pAP1 encodes a fusion protein of an Fv-antibody with a bacterial cell-wall protein. Bacteria carrying this plasmid express functional Fv-antibodies tightly bound to their surface. This should enable the selection of single cells with a fluorescence-assisted cell sorter (FACS) using labeled antigen or by adsorption to immobilized antigen. These vectors permit three major principles of the antibody response to be mimicked in E. coli: 1. Generation of a highly complex antibody repertoire; 2. Clonal selection procedures for library screening; and 3. The possibility of increasing a given affinity by repeated rounds of mutation and selection. PMID- 1285334 TI - Radiolabeled octreotide. What lessons for antibody-mediated targeting? AB - Octreotide is a synthetic analog of the peptide hormone somatostatin (SMS). A wide variety of tumors express enhanced numbers of SMS receptors, notably neuroendocrine tumors and lymphomas, but also some of the more common adenocarcinomas. Octreotide contains only eight amino acids, some of which are in the (D) configuration in order to enhance the stability of the molecule in vivo. Tyrosine and DTPA-containing analogs of octreotide have been synthesized and labeled with iodine-123 and indium-111, respectively, with the intention of targeting SMS receptor-containing tumors for diagnostic purposes. Both radiopharmaceuticals demonstrate a high sensitivity and specificity for these tumors, indicating a clinical role for these agents in management of these diseases. Lessons can be learned from the success of these agents when designing improved antibody-based molecules. Tumor uptake of radiolabeled octreotide is very rapid, occurring within minutes of administration. Blood clearance is also rapid, such that tumors are soon visible even in areas of high blood background. An interesting finding has been the differences between the pharmacokinetics of the iodinated and indium-labeled species. Although the majority of 123I-Tyr3 octreotide undergoes hepatobiliary excretion, 111In-DTPAPhe1-octreotide is eliminated predominantly by the kidneys. These results suggest that the smallest possible antibody-like tracers are likely to have advantages over native immunoglobulins and conventional Fab-like fragments. PMID- 1285336 TI - Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement. AB - Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE) whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF), a 70 kDa glycoprotein attached to the membrane of NHuE by a GPI anchor. IgG2a mAb anti-human DAF (IA10) immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre incubated with NHuE and inhibited their resistance to complement-dependent killing in vitro. Incubation of schistosomula with erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNHE) or SRBC, which are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polypeptide(s) present on the surface of the worm. PMID- 1285335 TI - Tegumental proteins of Schistosoma mansoni: complex biomolecules and potent antigens. AB - The passive transfer of monoclonal antibodies, direct vaccination and in vitro assays have all shown that antigens associated with the tegumental membranes of Schistosoma mansoni are capable of mediating protective immune responses against the parasite in animal models. Furthermore, the principal antigens are highly antigenic during natural infection in man and stimulate strong humoral and cellular responses although, at present, their role in mediating protective immune responses in man remains equivocal. This presentation will review the current state of knowledge of the structure and expression of the major antigenic tegumental proteins of the schistosome and will attempt to relate the relevance of their structural features to possible function both in terms of protective immunity and the parasite's ability to survive within the definitive host. A focus will be the recent advances that have been made in the identification of means of anchoring of the antigenic proteins to the tegumental membrane. In addition, the implications of the structural complexity of the tegumental proteins in terms of their possible utility in vaccination and diagnosis will be considered. PMID- 1285337 TI - The influence of cell culture and storage conditions on HIV-1 infectivity and fusogenic activity. AB - We have previously demonstrated that acidic medium inhibits the replication of HIV-1. The present study was designed to examine the effects of other growth conditions and infection of fibroblasts by coculture with HIV infected lymphoid cells. Several lymphoblastoid cell lines normally grown in RPMI-1640 were grown in Eagle's MEM. These cells supported virus replication to higher titres than did RPMI-1640. Peak viral titres were achieved within 24-48 h after newly infected or chronically infected cells were placed in fresh medium. When virus was stored in liquid medium either frozen or at higher temperatures, virus titres were retained for several months while frozen but decreased upon storage at 4 degrees C or higher. If cells were passaged after trypsinization in Ca(++)-depleted medium, then a decreased susceptibility of cells for HIV-1 by 2 log10 at 24 h post infection was observed. Infectivity of cell-free and cell-associated HIV-1 was measured using syncytium formation, reverse transcriptase activity and p24 antigen. No fusion between HIV-1 infected CD4+ lymphoblasts and CD4- fibroblasts was observed but HIV-1 infected lymphoid cells, even in the absence of syncytium formation, exerted a strong toxic effect on fibroblasts. This study extends previous findings that medium acidity was inhibitory to virus replication and survival. Thus, conditions for study of HIV must be well controlled in buffered medium so that misleading results are not obtained regarding virus multiplication and possibly regarding transmission to and pathogenesis in CD4- cells. PMID- 1285338 TI - Antigenic relationships among the members of adenovirus subgenera determined by monoclonal antibodies. AB - Epitope composition of human adenovirus (AV) serotype 13 (subgenus A), 19, 26 and 27 (subgenus D), as well as 41 (subgenus F) was studied with 23 selected monoclonal antibodies (MAbs) raised against different hexon types. With the help of three panels of MAbs great differences were shown in the epitope structure of subgenus D hexons. Comparing two AV13 strain hexons (a prototype strain and an intermediate strain), it was shown that the epitopes recognized by the MAbs were present in different combinations even on strains of the same serotype. Therefore the epitope composition of the subgenus D hexons seems to be heterogeneous. PMID- 1285339 TI - Immunodetection of keratin proteins in oral epithelial neoplasms. AB - Immunoperoxidase technique was used as an adjunct to routine Haematoxylin and Eosin Staining to assess the pattern of distribution and intensity of Keratin in Oral epithelial neoplasms. The specimens of papillomas, verrucous carcinomas and squamous cell carcinomas were studied. The broadly reactive polyclonal antikeratin antibodies were reacted with formalin fixed paraffin embedded sections. The staining of keratin proteins was found to be dependent upon the degree of differentiation of the tumour. It was observed that the pattern of keratin distribution was regular in papillomas while it was disturbed in verrucous carcinomas and squamous cell carcinomas. PMID- 1285340 TI - Endocrine events prior to puberty in heifers: role of somatotropin, insulin-like growth factor-I and insulin-like growth factor binding proteins. AB - We have utilized active immunization against growth hormone releasing factor (GRF) to investigate relationships among somatotropin (ST), insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP) and ovarian function in heifers. Active immunization against GRF (GRFi) has been demonstrated to abolish episodic release of ST and decrease serum concentrations of IGF-I. In initial experiments investigating onset of puberty, breeds of heifers differing in growth rate and reproductive traits (Angus, Charolais and Simmental) were immunized against GRF or served as controls (immunized against carrier protein, human serum albumin, HSAi). GRFi decreased rate of muscle and skeletal growth, but increased deposition of adipose tissue. In Angus and Charolais, but not Simmental heifers, GRFi at 6 mo of age significantly delayed onset of puberty beyond 18 mo of age. Retrospective analyses of serum IGF-I revealed that GRFi heifers reaching puberty at a normal age had greater pre-treatment (6 mo of age) IGF-I than GRFi heifers in which puberty was delayed. Collectively, these results strongly indicate that the bovine hypothalamic-hypophyseal-ovarian axis is particularly sensitive to changes in metabolism at or near 6 mo of age. Another series of experiments tested the hypothesis that lowering serum IGF-I via GRFi initially at 3 mo of age would increase the percentage of Angus and Simmental heifers not reaching puberty. Three mo old Angus and Simmental heifers were assigned to GRFi (n = 18), HSAi (n = 14) or received no treatment (controls, n = 16). HSAi and GRFi heifers were unilaterally ovariectomized (ULO) at 6 mo of age. As anticipated, GRFi at a younger age increased percentage of heifers not reaching puberty; over 75% of control and HSAi heifers reached puberty by 14 mo of age compared to 22% of GRFi heifers. Serum and follicular fluid (FFL; follicles < or = 4 mm) concentrations of IGF-I were suppressed by GRFi. Serum, but not FFL concentrations of IGF binding protein-2 (IGFBP-2) were greater in GRFi than in HSAi heifers. GRFi delayed puberty apparently by suppressing follicular growth because number of follicles < or = 7 mm was significantly lower in GRFi than in HSAi heifers. In conclusion, active immunization against GRF at 3 or 6 months of age delays puberty in beef heifers. Delayed puberty was preceded by suppression of follicular growth, and decreased concentrations of IGF-I in serum and follicular fluid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1285341 TI - Intracellular potentials of visceronociceptive neurons in posterior group of thalamic nuclei and its labeling with HRP intracellularly in cat. AB - The intracellular potentials (ICP) of 42 visceronociceptive neurons related to stimulating greater splanchnic nerve (SPL) in Posterior group of thalamic nuclei (PO) were investigated. We analyzed the electrophysiological features, such as amplitude of resting potentials and action potentials of the neurons. Following acquisition of electrophysiological data, (HRP) was injected into 3 neurons, whose responses were inducted by stimulating SPL (related neurons) and able to be inhibited by morphine intravenously. Two neurons revealing spontaneous discharges but are not able to evoke response by stimulating SPL (non-related neurons), also were stained by HRP. Two kinds of neurons, related and non-related ones, display different dendrite branching patterns. PMID- 1285343 TI - Management of premature ventricular contractions. PMID- 1285342 TI - Transbronchial biopsy in sarcoidosis: the role of immunohistochemical analysis for granuloma detection. AB - In this study 27 transbronchial biopsy specimens obtained from patients with clinical and/or laboratory features suggestive for sarcoidosis were analysed with conventional morphology and immunohistochemistry comparing the sensitivity and reproducibility of the two methods. A limited panel of monoclonal antibodies recognizing epitopes resistant to conventional fixation and embedment procedures were used (CD45R0, CD68, anti-cheratin, anti-collagen IV). All specimens were independently observed by two different pathologists. On the basis of the recognition of bona-fide noncaseating granulomas, 9 cases were uniformly judged as positive, 10 cases as negative, but 8 cases were considered doubtful. Immunohistochemical analysis reliably demonstrated the presence of epithelioid cells in 3 of these cases and absence in 5. These data suggest that the use of a limited immunohistochemical analysis can significantly improve histological diagnosis of sarcoidosis on small transbronchial biopsies using conventional routine material. PMID- 1285344 TI - Intraobserver and interobserver reproducibility of the FAB classification in acute leukaemia. AB - Intraobserver and interobserver reproducibility of FAB classification for acute leukaemia was assessed using the modified criteria of the FAB classification. Leishman stained peripheral smear and May Grunwald Giemsa stained bone marrow smears from 72 cases of acute leukaemia were used for this purpose. Cytochemical stains used were peroxidase, PAS and Sudan black B. Intraobserver and interobserver concordance/discordance was calculated. Kappa statistic was used to correct the chance expected agreement. Intraobserver and interobserver concordance was 76% which improved to 91% when cytochemistry was included. Lymphocytic/Nonlymphocytic concordance was 87.5% and 90% respectively for intraobserver and interobserver groups. PMID- 1285345 TI - Tissue plasminogen activator expression in endothelial cells exposed to cyclic strain in vitro. AB - The effects of cyclic strain on the production of tissue plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI-1) by cultured endothelial cells (EC) were examined. Human saphenous vein EC were seeded in selective areas of culture plates with flexible membrane bottoms (corresponding to specific strain regions) and grown to confluence. Membranes were deformed by vacuum (-20 kPa) at 60 cycles/min (0.5 s strain alternating with 0.5 s relaxation in the neutral position) for 5 days. EC grown in the periphery were subjected to 7-24% strain, while cells grown in the center experienced less than 7% strain. The results show a significant increase in immunoreactive tPA production on days 1, 3 and 5 compared to day 0 in EC subjected to more than 7% cyclic strain. There was no significant elevation of tPA in the medium of EC subjected to less than 7% strain. tPA activity could only be detected in the medium of EC subjected to more than 7% cyclic strain. PAI-1 levels in the medium were not significantly different in either group. In addition, immunocytochemical detection of intracellular tPA and messenger ribonucleic acid (mRNA) expression of tPA (assessed by the reverse transcriptase polymerase chain reaction utilizing tPA specific sense and antisense primers) was significantly increased in EC subjected to more than 7% cyclic strain. We conclude that a 60 cycles/min regimen of strain that is greater than 7% can selectively stimulate tPA production by EC in vitro and may contribute to the relative nonthrombogenicity of the endothelium in vivo. PMID- 1285346 TI - A porcine model for adipose tissue-derived endothelial cell transplantation. AB - The transplantation of endothelial cells represents a technology which has been suggested for applications ranging from improvement in function of implanted vascular devices to genetic therapy. The use of microvascular endothelial cell transplantation has seen increased use both in animal studies as well as clinical use. This report describes our techniques for the isolation and establishment of initial cultures of microvascular endothelial cells derived from porcine fat. A variety of anatomic sites within the pig were evaluated to determine the appropriateness of different sources of fat for endothelial cell isolation. The properitoneal fat was determined to be optimal due to the predominance of endothelium in this tissue and the ease of isolation of microvascular endothelium following collagenase digestion. The study of endothelial cell transplantation in the porcine model is now possible using the methods described for adipose tissue derived microvessel endothelial cell isolation. PMID- 1285347 TI - [Thrombotic thrombocytopenic purpura]. PMID- 1285348 TI - [Symptomatic treatment of pain in cervico-facial cancers]. AB - Pain is frequent in patients presenting cervico-facial cancers. It can be acute or persistent, or present at the morbid entity known as chronic pain. The specific anatomical site and the often poor environment explain that the physical disability related to pain is increased by multiple psychosocial problems. Multidisciplinary care management by several actors is required and can be facilitated by a simple decision-making model. The schema presented can be used to prompt discussion and criticism. It needs constant improvement and extensions in order to reach a consensual attitude towards this king of suffering but also towards other situations of pain care management frequently encountered in cancer patients as well as those with other pathologies. PMID- 1285350 TI - Neovascular glaucoma and intraocular pressure: I. Pathogenesis of increased intraocular pressure and therapy (a review of historical and current therapeutic modalities). AB - The pathogenesis of neovascular glaucoma is summarized. Elevation of intraocular pressure is mostly associated with mechanical obstruction of the anterior chamber angle by the fibrovascular membrane, as well as with an enhanced ultrafiltration from the newly formed vessels. Drug therapy is insufficient. Standard filtering surgery is unsatisfactory with regard to the control of intraocular pressure and hemorrhagic complications. The drainage implants appear to be promising. Panretinal photocoagulation is unfavorable due to turbidity of the optical media. Favorable therapeutical results were achieved with cryosurgical techniques, namely panretinal cryocoagulation, combined with cyclocryocoagulation. Cyclocryocoagulation alone accounts for a high percentage of complications and therapeutical results are not convincing. PMID- 1285349 TI - Self-expanding mesh stent for endoscopic palliation of rectal obstructing tumors: a preliminary report. AB - The endoscopic insertion of self-expanding mesh stents in four patients affected by obstructing rectal malignant tumors is reported. The preliminary experience shows that, in the short term, normal defecation was achieved, with no complications. Longer follow-up is necessary to evaluate the duration and the quality of the palliative effect. PMID- 1285351 TI - Identification of uncultured microorganisms: expanding the spectrum of characterized microbial pathogens. AB - The combination of enzymatic nucleic acid amplification techniques with 16S rRNA based molecular phylogeny has brought about a new approach to the identification of microbial pathogens that can not be cultivated in the laboratory. The applications of this experimental approach to bacillary angiomatosis and to Whipple's disease have revealed the presence of two previously uncharacterized organisms. These results suggest the existence of a far greater microbial diversity among human pathogens than has been so far appreciated with culture dependent methods. PCR-based studies of aquatic environmental microbial communities have already reached similar conclusions. As a result, new and provocative questions are raised concerning the association of amplified 16S rRNA sequences with diseased tissue. The answers must await the results of further investigations and the expansion of sequence data bases. PMID- 1285352 TI - Screening Moroccan infants using the Wolanski Gross Motor Evaluation: a pilot study. AB - The purpose of this study was to examine the possibility of using the Wolanski Gross Motor Evaluation (WGME), to effectively screen Moroccan infants for motor disabilities. Additionally, the appropriateness of Polish norms for use with Moroccan children was considered. One hundred and twenty subjects, 15 females and 15 males from four age groups (three, six, nine and 12 months), were recruited from well-baby clinics in Marrakech. Subjects were tested for gross motor maturity using the WGME. Differences were found in the sequence of skill acquisition between the Polish norms and the Moroccan sample in sitting, standing, and rolling skills. Differences were also found in the rate of development between the Moroccan and Polish infants. No differences were found between Moroccan females and Moroccan males in the rate of motor development. Results from this study indicate that the grids used to score the WGME are not applicable to Moroccan infants, and would need to be modified for use with a Moroccan population. PMID- 1285353 TI - Angiofollicular lymph node hyperplasia: a comparison of unicentric, multicentric, hyaline vascular, and plasma cell types of disease by morphometric and clinical analysis. AB - A morphometric and clinical analysis of 47 cases of angiofollicular lymph node hyperplasia (AFLH) demonstrated morphometric differences between plasma cell (28 cases) and hyaline vascular (19 cases) AFLH. Twenty-one AFLH cases were unicentric, and 26 cases were multicentric. Plasma cell types of AFLH, defined by standard morphologic and objective morphometric assessment, were associated with systemic clinical and laboratory abnormalities. Unicentric or hyaline vascular AFLH was amenable to surgical therapy, and multicentric or plasma cell AFLH without neuropathy was amenable to steroid treatment or chemotherapy with good prognoses. Multicentric or plasma cell AFLH with neuropathy was associated with resistance to steroids and chemotherapy and with a poor prognosis. PMID- 1285354 TI - Expression of vimentin in proliferating and damaged bile ductules and interlobular bile ducts in nonneoplastic hepatobiliary diseases. AB - Biliary epithelial cells express characteristically cytokeratin in their cytoplasm in normal and diseased livers. The present study disclosed that vimentin was frequently expressed in the cytoplasm of proliferating and damaged bile ductules and interlobular bile ducts, while their normal counterparts were negative for vimentin. Although this expression itself seemed nonspecific to any of the hepatobiliary diseases examined, bile ductules and interlobular bile ducts were frequently positive in chronic cholestatic and necroinflammatory liver diseases. In biliary epithelial cells, vimentin was localized around the nucleus or in the subnuclear regions, when present. Immunoelectron microscopically, reaction products for vimentin and for cytokeratin were found on bundles of intermediate filaments in the cytoplasm of biliary epithelial cells. The former was found mostly in the paranuclear and subnuclear regions, while the latter detected around the desmosomes, in addition to the paranuclear cytoplasm. Vimentin and cytokeratin were also seen together under immunoelectron microscopy on the same intermediate filaments. It seems likely that aberrant expression of vimentin in bile ductules and interlobular bile ducts and heterogeneous antigenic expression of intermediate filaments in the same biliary epithelial cells may be related to proliferation of, reorganization of, or damage to the ductular and ductal biliary cells in a variety of hepatobiliary diseases. PMID- 1285355 TI - Paranuclear blue inclusions in metastatic undifferentiated small cell carcinoma in the bone marrow. AB - Paranuclear blue inclusions (PBIs) are frequently identified within metastatic undifferentiated small cell carcinoma (SCC) cells on air-dried bone marrow aspirates stained with Wright's stain. To determine the sensitivity and specificity of this finding, 116 bone marrow aspirates containing metastatic neoplasms were evaluated for the presence and frequency of PBIs. Bone marrow specimens included 47 cases of metastatic SCC of the lung, 13 cases of large cell lymphoma, 19 cases of neuroblastoma, five cases of small, noncleaved cell lymphoma, seven cases of rhabdomyosarcoma, three cases of Ewing's sarcoma, three cases of other sarcomas, and 19 cases of non-small cell carcinoma (adenocarcinoma). PBIs were identified in 40 of 47 (85%) cases of SCC and their frequency varied from 0 to 24% of tumor cells among different cases. In approximately half the cases of SCC, PBIs were identified in 1 to 4% tumor cells; and in eight cases, PBIs were present in 5% or more of tumor cells. PBIs were also identified in two of seven (29%) cases of rhabdomyosarcoma and one case of malignant peripheral nerve sheath tumor, but they were not seen in Ewing's sarcoma, small non-cleaved cell lymphoma, large cell lymphoma, neuroblastoma, or non-small cell carcinoma. In addition, PBIs were not seen in alcohol-fixed, Papanicolaou-stained cytology specimens containing SCC. Ultrastructurally, PBIs may represent phagocytized nuclear/cellular material. PBIs are a feature of small cell carcinoma on air-dried, cytologic material stained with Romanowsky type stains. Their presence may provide diagnostic information with regard to the differential diagnosis of metastatic SCC in the bone marrow. Future studies evaluating non-bone marrow Wright's stained fine-needle aspiration specimens are needed to determine if PBIs are useful in distinguishing SCC from other poorly differentiated tumors in the cytology laboratory. PMID- 1285356 TI - Inhibition of tobacco nitrite reductase activity by expression of antisense RNA. AB - A tobacco nitrite reductase (NiR) cDNA and its corresponding gene were isolated from cDNA and genomic libraries. An NiR antisense mRNA was expressed in transgenic tobacco under the control of a double 35S promoter. Transformants were obtained on a medium containing ammonium as the sole source of nitrogen. One plant growing normally on ammonium but displaying drastically reduced development and chlorotic leaves when grown on nitrate as the sole source of nitrogen was studied further. This plant accumulated nitrite fivefold over wild-type level and showed reduced amounts of ammonium (11% wild-type level), glutamine (19%), and total protein (8%). NiR mRNA and activity were below detectable levels. Under these conditions, nitrate reductase (NR) activity and mRNA were overexpressed, suggesting that N-metabolites resulting from nitrate reduction are responsible for the repression of the expression of the NR gene, independently from the presence or absence of a functional NR protein. PMID- 1285358 TI - [Pancreatic endocrine tumor with metastases and increase of alpha-fetoprotein. A case report]. AB - The authors report the case of a 48 years old man presenting a pancreatic islet cell carcinoma (gastrinoma) with liver, nodes and peritoneal metastases, associated with an elevated alpha-fetoprotein (AFP) concentration. Incomplete remission was first obtained with a chemotherapy using Streptozotocin combined with 5-Fluorouracil, in association with a Somatostatin analogue (SMS 201-995). But when relapses occur, another chemotherapy was not so effective. Serum gastrin and AFP levels had the same evolution and appear to have the same interest to follow the course of the disease. PMID- 1285357 TI - [Occurrence of an epidermoid bronchial carcinoma 8 years after a small cell carcinoma treated with only 3 courses of chemotherapy]. AB - A case of squamous cell bronchial carcinoma developed 8 years after treatment of a small cell carcinoma is reported. Three hypotheses may be put forward to explain this sequence of events: either a squamous cell line was selected from within an initially mixed tumour, or the small cell carcinoma differentiated into a squamous cell carcinoma, or a second primary tumour developed independently. All this is purely speculative, but the long doubling time implied by the first two hypotheses would be in favour of a second primary tumour. PMID- 1285359 TI - Monitoring the efficacy of temephos application and use of fine mesh nylon strainers by examination of drinking water containers in guineaworm endemic villages. AB - Application of temephos in unsafe water sources for destroying cyclops, the intermediate hosts of guineaworm, and distribution of fine mesh nylon strainers for promoting prophylaxis against guineaworm are accepted methods of guineaworm control in different endemic countries. The existing methods of monitoring the efficacy of these guineaworm control methods are not fully informative. Examination of drinking water stored at household levels for presence of cyclops with or without Dracunculus larvae can provide information on the efficacy of these control/prophylactic methods, besides serving as a means of interpersonal health education to the community. This paper presents observations carried out in two villages in peninsular India in 1991, which revealed that while in one village complete absence of cyclops from stored water containers was attributable to the use of temephos in the village and straining of drinking water, in the other village, with no temephos application, 15.6 per cent of containers contained varying numbers of cyclops in them. Implications of these observations for guineaworm eradication activities are discussed. PMID- 1285360 TI - The response of regulatory peptides to moderate hypoglycaemia of short duration in type 1 (insulin-dependent) diabetes mellitus and in normal man. AB - The changes in plasma gastrin-releasing peptide (GRP), arginine vasopressin (AVP), neuropeptide Y (NPY), corticotropin releasing hormone (CRH), galanin, ACTH, cortisol, delta sleep-inducing peptide (DSIP), adrenaline, noradrenaline and pancreatic polypeptide (PP) were measured after 5 and 15 minutes of acute insulin-induced moderate hypoglycaemia (2.0 mmol/l) in 10 patients with Type 1 diabetes mellitus with no autonomic neuropathy and in 10 healthy subjects. Plasma catecholamine and PP levels rose in both groups in response to hypoglycemia and the secretory response of ACTH was lower in the diabetic subjects (p < 0.01). GRP concentrations increased during hypoglycaemia (p < 0.01) while a reduction in AVP occurred at the start of hypoglycaemia (p < 0.001). The plasma AVP concentrations were higher in the diabetic group compared with those in the normal group (p < 0.05). The NPY concentrations were higher in the normal subjects (p < 0.05) but no change in the mean level occurred in either group during hypoglycaemia. No group differences or changes in mean plasma concentrations were found for galanin, DSIP and CRH. These observations support the view that regulatory peptides, if involved in glucose homeostasis, may rather have a modulatory effect than a direct action in restoring normoglycaemia. PMID- 1285361 TI - [Acute-phase proteins in colorectal cancer]. PMID- 1285362 TI - [Biochemical profile of Senegalese women on oral contraceptives]. AB - By its many advantages, pills are one of the most used methods in the world and in Senegal. On the other hand, exist side effects which can limit their utilization. Our study concern 35 women using between 12 and 36 months mini pills, which might produce low side effects. In our users, biochemical parameters are modified but not pathologic. By our results, we think that in the following 5 or 10 years, these alterations might increase; so, we raise the alarm and propose a biological following up of the oral contraceptive users. PMID- 1285363 TI - Child health surveillance. Surveillance of the child under 5. AB - 1. General health checks should be made at the following times as outlined in these guidelines: Initial neonatal assessment 7-10 day check, 6-week check, 7-9 months: general examination with particular attention to hearing and vision, 18 24 months: check with special attention to gait, speech and understanding, 36-42 months: general examination and developmental assessment, 2. Parental concern over a child's special senses should be carefully followed up and investigated. 3. Immunization schedules are as follows: 0-2 months: Neonatal BCG (variable depending upon local public health policy and countries of origin of local residents) 2 months: 1st diphtheria, tetanus, pertussis (DTP) and polio, Hib 3 months: 2nd DTP and polio, Hib 4 months: 3rd DTP and polio, Hib 12-18 months: MMR 4 years: Preschool DT and polio There are very few contra-indications. 4. Failure to thrive may be caused by infection, a metabolic problem or emotional factors. It is most commonly revealed by: poor weight gain over a period of time rapid weight loss. These guidelines are in two parts. The first part outlines a programme of surveillance which we hope all general practitioners will find helpful. The second part is more applicable to practices which organize their own child health clinics. PMID- 1285364 TI - The silence of the X. PMID- 1285365 TI - Submucosal glands are the predominant site of CFTR expression in the human bronchus. AB - We have used in situ hybridization and immunocytochemistry to characterize the cellular distribution of cystic fibrosis (CF) gene expression in human bronchus. The cystic fibrosis transmembrane conductance regular (CFTR) was primarily localized to cells of submucosal glands in bronchial tissues from non-CF individuals notably in the serous component of the secretory tubules as well as a subpopulation of cells in ducts. Normal distribution of CFTR mRNA was found in CF tissues while expression of CFTR protein was genotype specific, with delta F508 homozygotes demonstrating no detectable protein and compound heterozygotes expressing decreased levels of normally distributed protein. Our data suggest mechanisms whereby defects in CFTR expression could lead to abnormal production of mucus in human lung. PMID- 1285366 TI - Histamine release and SOD, allopurinol and ranitidine pretreatment in haemorrhagic shock in the rat. AB - Histamine release have been demonstrated in haemorrhagic shock. There are some observations that oxygen free radicals can cause histamine release. Oxygen free radicals play a role in the pathogenesis of gastric mucosal lesions. The goal of this study was to determine whether ranitidine or SOD and allopurinol pretreatment modify the histamine release during and after the haemorrhagic shock in the rat. In the anaesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The shed blood was reinfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, histological grading was made. Blood samples taken from the carotid artery were examined by radioimmunoassay (IMMUNOTECH) to determine the plasma histamine level. Plasma histamine level did not change significantly during the preparative surgery, but there was a significant increase of histamine level by the end of shock period. After the reinfusion of the blood the plasma histamine remained essentially at the same level for five min. Oxygen free radicals did not cause an important histamine release. By the end of the experiment the histamine level decreased dramatically. Ranitidine, allopurinol and SOD pretreatment provided significant protection against the gastric mucosal lesions. Allopurinol and SOD did not influence significantly the histamine level. Ranitidine caused significant histamine release immediately after the injection and every histamine value was significantly higher in this group except for the final value which was lower than the control one. The oxygen free radicals were not found as endogenous histamine releasers in this study. PMID- 1285367 TI - Cholinergic neurons are involved in the effect of substance P on the circular muscle of the guinea pig small intestine. AB - The mode of action of the excitatory neuropeptide substance P was studied on the circular muscle of the guinea pig ileum in vitro. Atropine or tetrodotoxin strongly inhibited substance P-induced phasic contractions. The atropine resistant part of the circular response was blocked by tetrodotoxin. A newly developed method for quantitative evaluation revealed a rightward displacement of the substance P concentration-response curve, as well as a strong depression of the maximum effect, in the presence of atropine. These results indicate that cholinergic (and probably also non-cholinergic) excitatory neurons mediate phasic contractions due to substance P. The tonic component of the substance P-induced contraction was slightly reduced by atropine. PMID- 1285368 TI - The effect of somatostatin, gabexate mesilate and dextran 40 on the microcirculation in sodium taurocholate-induced pancreatitis. AB - In vivo microscopy was performed to assess the effect of dextran 40, gabexate mesilate and somatostatin on the microcirculation in sodium taurocholate-induced pancreatitis in rats. Intraductal infusion of 0.4 ml of a 4% solution of sodium taurocholate decreased capillary blood flow, induced capillary stasis and increased vascular permeability in the head of the pancreas. Dextran 40, gabexate mesilate and somatostatin improved capillary blood flow in the initial phase of acute pancreatitis significantly and prevented stasis in 5 of 9, 3 of 8 and 7 of 10 (p < 0.05) cases. Only dextran 40 reduced the increase of vascular permeability. Decrease of capillary blood flow, capillary stasis and vascular permeability changes are important factors contributing to the pathogenesis of sodium taurocholate-induced pancreatitis. Dextran 40, gabexate mesilate and somatostatin exert a beneficial effect on the microcirculatory changes in this model of acute pancreatitis. PMID- 1285369 TI - Antiinflammatory effect of a protein kinase C inhibitor (K-252a) on the development of the dextran-induced paw edema in the rat (preliminary results). AB - The effect of a metabolite of Nocardiopsis sp. as a protein kinase C inhibitor from microbial origin was investigated on the onset and development of dextran induced paw edema in the rat. It was published that this compound (K-252a) interferes with histamine release from mast cells, while dextran-induced paw and nose edema are induced by vasoactive agents, like histamine etc., released from the disrupted mast cells. The antiinflammatory effect of the K-252a is effectuated by the inhibition of protein kinase C. Groups of male Wistar rats with 180-200 g b.w. were used; each group consisted of 10-10 rats. The following groups were consisted: rats given orally DMSO (control), rats given 1 mg/kg, or 3 mg/kg b.w. of K-252a dissolved in DMSO and given p.o. one hour before dextran injection. Dextran (BDH Chem. LTD, molW: 200.000, England) was injected intraperitoneally in 10% solution, in a dose of one ml/100 g b.w. Volume of the hind leg was measured by a mercury plethysmometer. Time-sequence of the edema was followed. Increase in volume of hind leg paw was related to its 0-min volume in %. Results were analyzed by the Kruskal-Wallis-test. Edema of the legs and noses appeared in each of the control rats in one hour. The 1 mg/kg dose of K-252a retarded the appearance of the edema by 1 hour, the 3 mg/kg dose, however, prevented its onset for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285370 TI - Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P. AB - In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response. PMID- 1285371 TI - [Blood conservation in heart surgery]. PMID- 1285372 TI - The incompatibility complex of H. plasmids. AB - This review deals with the general properties of the very large transfer thermosensitivity R. factor belonging to the H. incompatibility complex. This group is of particular interest not only because their temperature sensitivity transfer system but also for the number as well as distinctive resistance determinants being accumulate by them, and their prevalence in Salmonella serotypes and in other Gram-negative non-pathogenic bacteria both in man and animals. PMID- 1285373 TI - [Upper digestive hemorrhage in acute pancreatitis]. AB - We proposed to investigate the following parameters regarding upper gastrointestinal hemorrhage occurring in the patients with acute pancreatitis: incidence, form of manifestation, severity, correlated to the clinical and morpho pathological form of acute pancreatitis, cause (direct causality or morbid association). The study was carried out on the inpatients of the internal medicine and surgery units over a period of one year. For sake of accuracy the study also included the cases submitted to necropsy over a period of 5 years. The practical experience has revealed that though gastrointestinal bleeding is not a frequent complication--9.1% in the patients with acute pancreatitis and 36.3% of the necropsied cases--it is often severe, which imposes the early recognition for its adequate management. PMID- 1285374 TI - [Chromo-colposcopic images during oral contraception]. AB - The Authors report chromocolposcopic pictures with AZEA (Azure 2 + alcohol soluble eosine + ethanol) and related histologic pictures in six women under oral contraception. Columnar epithelium develops violet or blue-violet areas histologically corresponding to endocervicitis. Aceto-white epithelium develops reddish color in case of medium-mature metaplasia, brown-violet in case of mature metaplasia, lilac in case of superficial koilocytosis on metaplasia. Native epithelium appears dark brown, or yellow-brown in case of koilocytosis. PMID- 1285375 TI - The communicative Effectiveness Index: its use with South African stroke patients. AB - The functional communication of a group of 28 South African stroke patients was examined using the Communicative Effectiveness Index (CETI). It was translated into Afrikaans, Sotho and Zulu and administered to the significant others of 22 aphasic patients with left hemisphere damage and 6 patients with right hemisphere damage. Results were related to the results of standardized language testing and to case history factors such as cultural factors and time since onset. The CETI was readministered in the case of eight of the aphasic subjects after a mean period of six months in order to assess its sensitivity to recovery. Results showed that the CETI seems applicable across different language groups, that it is sensitive to change across time as well as sensitive to the communication disorders resulting from both right and left hemisphere damage. Further it appears to correlate well with overall level of severity. It does not appear to differentiate patients in terms of time since onset. Its potential use as a relatively culture free assessment tool in the South African context is discussed. PMID- 1285376 TI - Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 16 non-Japanese cases. AB - Kabuki make-up (Niikawa-Kuroki) syndrome has been described mainly in Japanese patients. In this paper we report sixteen new cases from Europe and North America, suggesting that Kabuki make-up syndrome may be more common outside of Japan than supposed. Their features are compared with those of the Japanese patients and most of our findings are similar to those previously reported. The facial phenotype is specific and easily recognizable, regardless of ethnic origin. Postnatal growth retardation and mild mental retardation are confirmed to be cardinal manifestations of the syndrome. Skeletal anomalies were present in all cases but most of the radiological changes were non-specific. The specificity of metacarpophalangeal pattern profile is not confirmed. Conversely, dermatoglyphic analysis is helpful in the diagnosis of this condition. Two differences have emerged between the Japanese patients and those in this study. Firstly, two-thirds of the patients in this series had significant neurological dysfunction other than mental retardation. Secondly, joint hypermobility appears more common in non-Japanese patients. Confirmation of these findings requires further studies. PMID- 1285377 TI - [Effect of acute and chronic administration of L- thyroxine and methimazole on blood levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in plasma of rats]. AB - The effects of hyperthyreosis induced by the administration of thyroxine and hypothyreosis induced by the administration of methimazole on the levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in low-platelet blood plasma have been studied in Wistar rats. Thyroxine administration (120 micrograms/kg/24 h, intraperitoneally) lasting 7 days caused a decrease in serotonin concentration by 38 per cent. The level of this amine in rats receiving thyroxine during three months was elevated by almost three times. Tryptophane concentration did not change following thyroxine administration. Methimazole administration lasting 14 days (oral dose 15 mg/kg/24 h) caused an increase in tryptophane concentration by 34 per cent and in serotonin concentration by 24 per cent. Long-term hypothyreosis induced by methimazole administration lasting three months caused an 39 per cent increase in tryptophane and 38 per cent increase in serotonin concentration. Neither hyperthyreosis induced by thyroxine administration nor hypothyreosis induced by methimazole++ caused any changes in the concentration of 5-hydroxyindoleacetic acid. The importance of serotonin in pathogenesis of clinical symptoms accompanying the states of deficit or excess of thyroid hormones needs further elucidation. PMID- 1285378 TI - Clinical applications of radioimmunoassay of the alpha-subunit of glycoprotein hormones. AB - The radioimmunoassay of alpha-subunit adapted in our laboratory was widely evaluated. Three different antisera (anti-pituitary alpha-subunit, anti-alpha-TSH and anti-alpha-hCG), the labelled preparations of pituitary alpha-subunit and alpha-hCG, and cross-reactivity with intact glycoprotein hormones (MRC standards of LH, FSH, hCG and TSH) were tested for their potential influence on the results of the assay. The basal levels of alpha-subunit were measured in 48 healthy young men, 48 normally menstruating women, 33 menopausal women, 37 pregnant women and 70 patients with pituitary adenoma. In addition a possibility of pulsatile secretion of alpha-subunit was investigated in 9 healthy young women, the ranges of alpha-subunit concentrations found were as follow (means +/- SD): 1.2 +/- 0.4 micrograms/l--in young men, 1.1 +/- 0.4 micrograms/l--in young women, 3.2 +/- 0.7 micrograms/l--in postmenopausal women, 1-54 micrograms/l--in pregnant women, and between 2.6 and 44.0 micrograms/l in 14 of 70 patients with pituitary adenoma. There were good correlations of results for 3 different antisera and their cross reactivity with LH, FSH, hCG and TSH were just as low. In conclusion, the alpha subunit assay appears clinically useful and should be widely applied in routine endocrinological diagnostics. PMID- 1285379 TI - [Alcohol decreases the alpha subunit, LH and testosterone secretion in response to LH-RH]. AB - In our previous study we showed that alcohol disturbed the circadian rhythms of LH, testosterone and its conversion to DHT. To determine the effect of LH-RH on pituitary-gonadal function before and after alcohol, 11 male volunteers aged 24 29 years (mean 25.5) were investigated. Blood for hormonal estimations was withdrawn before and 20, 30, 60, and 120 min after LH-RH. In every case, the LH RH test was performed twice: 6 hours after placebo and, a week later, 6 hours after alcohol administered orally, in dose of 1.0 g/kg bw. The LH, FSH, alpha subunit and testosterone concentrations were measured with radioimmunological methods. RESULTS: It was shown that alcohol significantly inhibited LH (p < 0.05), alpha-subunit (p < 0.02) and testosterone (p < 0.001) response to LH-RH stimulation, but not that of FSH. PMID- 1285380 TI - Recent advances in the mechanism of action of cyclosporine and FK506. AB - The immunosuppressants cyclosporine and FK506 (tacrolimus) are extremely potent inhibitors of T-lymphocyte activation. Recent studies have shown that these agents are actually prodrugs that become active only when bound to specific members of the cyclophilin or FK506 binding protein receptor gene families. The cyclosporine-cyclophilin or FK506-FK506 binding protein receptor complexes interact with a key component of the T-cell antigen receptor signal transduction pathway, the calcium-calmodulin-dependent phosphoprotein phosphatase calcineurin. The drug-receptor complexes inhibit the phosphatase activity of calcineurin and thereby prevent transcriptional activation of the interleukin-2 gene. PMID- 1285381 TI - Peripheral blood stem cell mobilization by chemotherapy with and without recombinant human granulocyte colony-stimulating factor. AB - Chemotherapy can serve as a stimulus for mobilizing hematopoietic progenitor cells to the peripheral blood for harvest via leukapheresis. Mobilized peripheral blood stem cells (PBSC) support rapid hematologic reconstitution after bone marrow aplasia induced by intensive myelosuppressive treatments. Our purpose was to develop effective mobilization regimens allowing collection of large quantities of PBSC. We administered high-dose cyclophosphamide (HDC, 4 gm/m2) or cyclophosphamide (4 gm/m2) plus etoposide (600 mg/m2) (HDCE) in a nonrandomized, sequential fashion to 94 patients with breast cancer, lymphoma, and other malignancies with collection of PBSC via leukapheresis during white blood cell (WBC) recovery from nadir counts. Each apheresis product was analyzed for total nucleated cell number, granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Twenty-four additional patients with comparable pretreatment characteristics received HDCE plus recombinant human granulocyte colony stimulating factor (HDCE+G) after chemotherapy through the end of apheresis. Patients receiving HDC were matched for age, sex, and disease but were more heavily pretreated. HDCE was superior to HDC in mean daily CFU-GM and CD34+ yield (p < 0.05), even when groups were adjusted for performance status and amount of prior therapy. HDCE+G led to 3.7 times more CFU-GM and 4.7 times more CD34+ cells than HDCE. Target PBSC yield, defined as > 20 x 10(4) CFU-GM/kg and >4 x 10(8) cells/kg, was achieved by 92% of HDCE+G patients after a median of three aphereses, 56% of HDCE patients after five aphereses, and 16% of HDC patients after six apheresis (p < 0.0001). Prior chemotherapy inversely correlated with the quantity of PBSC harvested regardless of regimen utilized. Our results demonstrate effective chemotherapy regimens for harvesting hematopoietic progenitors in a diverse patient population. HDCE+G produced the highest number of progenitors, suggesting that increasing dose intensity and adding rhG-CSF enhances mobilization. Correlation between cumulative CD34+ and CFU-GM allows real-time flow cytometric analysis of the number of aphereses required to harvest target numbers of PBSC. PMID- 1285382 TI - Defining a therapeutic dose of peripheral blood stem cells. AB - Peripheral blood stem cells (PBSC) are now used extensively to provide rapid and durable hematopoietic reconstitution following supralethal myeloablative therapies. A major clinical issue is the quantitation of the cells responsible for reconstitution. We review here published reports of transplants using the measurement of mononuclear cells and granulocyte-macrophage colony-forming units (CFU-GM) to quantitate PBSC. In addition, we present data from three institutions where hematopoietic recovery is correlated with doses of CFU-GM or CD34+ cells. These data suggest doses of 20 x 10(4) CFU-GM or 2 x 10(6) CD34+ cells/kg body weight that provide rapid engraftment of neutrophils and platelets. PMID- 1285383 TI - On the immunopathology of multiple sclerosis lesions. AB - Active chronic multiple sclerosis (MS) lesions contain numerous T-200 and leukocyte function associated antigen (LFA)-1-positive infiltrating cells. Macrophages at the lesion edge are stained for immunoglobulins (Ig), Class I and Class II major histocompatibility complex (MHC) antigens, for interferon (IFN) alpha and for the beta-2 integrin adhesion molecule gp 150/95. In the periplaque area, numerous CD2, CD4, and CD8 positive T cells and cells reactive for the CD45RO phenotype of memory cells and for gamma/delta T cell receptors are located between MHC-positive glial cells. White matter at the edge is diffusely stained for intercellular adhesion molecule (ICAM)-1 and LFA-3. Remote from lesions, labeling for Class II MHC, ICAM-1 and LFA-3 was enhanced on some endothelial and glial cells. These findings indicate that adhesion molecules are involved in the formation and possibly also in the reactivation of MS lesions. PMID- 1285384 TI - Reduced CD4-CD8 T cell ratios in patients with Wegener's granulomatosis. AB - All of the patients with Wegener's granulomatosis (WG), whom we studied, exhibited abnormalities in lymphocyte subsets. We used two-color immunofluorescence flow cytometry to examine the lymphocyte subset alterations. WG group showed a decrease in the percentage of CD4+ cells and an increase of CD8+ cells. Within the NK cell family, functionally unidentified CD8+57+ cells were markedly increased in number. The disproportion of these lymphocyte subsets (CD4+ decreases, CD8+57+ increases) was similar to that seen in Acquired Immunodeficiency Syndrome (AIDS) and AIDS related complex (ARC). PMID- 1285385 TI - Protein folding pathways determined using disulphide bonds. AB - The best-characterized model pathway of protein folding, that of disulphide bond formation in the small protein BPTI, has been questioned recently. A reinvestigation of that pathway, using alternative methods, concluded that the intermediates with non-native disulphide bonds accumulated to lower levels than previously had been observed. On this basis, a revised pathway was proposed that simply omitted those intermediates. Even if totally correct, however, the new observations are not inconsistent with the important characteristics of the original pathway and even confirmed many of them. Certain crucial observations that were the experimental basis for the original pathway were ignored, and these observations invalidate the revised pathway. PMID- 1285386 TI - [Chlormadinone Acetate Reference Standard (Control 881) of National Institute of Hygienic Sciences]. AB - Chlormadinone acetate was tested for the preparation of the "Chlormadinone Acetate Reference Standard (Control 881)". Analytical data obtained were as follows: loss on drying, 0.00%; infrared spectrum, 1740, 1715, 1658, 1604, 1587, 1256, 1244 cm-1; ultraviolet spectrum, lambda max = 284 nm; absorbance, E1cm1% (284 nm) = 539-549; optical rotation, [alpha]D20: -12.1 degrees; melting point, 214.6 degrees C; thin-layer chromatography, contaminants were not detected until 300 micrograms; high-performance liquid chromatography, one contaminant was detected. On the basis of the above results, this material was authorized as the National Institute of Hygienic Sciences Reference Standard (Control 881). PMID- 1285388 TI - [Receptors of glycoprotein hormones]. PMID- 1285387 TI - [Lectin reactivity in the kidney of newborn rat compared to adult rat]. AB - The distribution of binding sites for 13 lectins with different specificities was studied in adult and new-born rat kidney tissue by staining paraffin sections with the ABC method. Various segments of the uriniferous tubule in both rats showed differential affinity for lectins. None of these lectins showed any reactivity with the immature developmental components of kidney like S-shaped bodies and mesonephric blastema. In the new-born rat kidney, the reactivity of 4 lectins (DBA, PNA, SBA and WGA) on the proximal tubules was very weak compared with the adult rat. Seven lectins (RCA-I, BSL-I, WGA, UEA-I, PHA-E, PSA, LCA), which stained the glomerulus of adult rats, failed to react with glomerular turf in new-born rat kidneys. On the contrary, 4 lectins (RCA-I, WGA, UEA-I and PHA-E) out of these 7 lectins stained the surface of podocyte in the new-born kidney. Colloidal iron stained glomerular turf in adult rats also showed less reactivity in immature glomerulus. These results suggested that changes in lectin binding reactivity are associated with the development and the differentiation of the rat kidney. PMID- 1285389 TI - MHC class II determinants on peripheral blood monocytes from newly diagnosed IDDM patients. AB - The expression of MHC class II determinants (HLA-DR, HLA-DP and Ia7) on peripheral blood monocytes (OKM1+ cells) was studied in 20 children with newly diagnosed IDDM. Monocytes of 10 children with IDDM and familial predisposition showed a statistically significant increase of HLA-DR expression when compared to control group (10 healthy children). There were no significant differences concerning Ia7 expression. HLA-DP expression was similar in all studied groups. PMID- 1285390 TI - [Contemporary views on treatment with thyrostatic drugs for hyperthyroidism associated with Graves' disease]. PMID- 1285392 TI - [Focused extracorporeal pyrotherapy. Initial experimental results]. AB - The objective of this study was to develop an apparatus allowing the generation of a high temperature (exceeding 80 degrees C) in a precise focus (20 mm x 2 mm) by means of extracorporeal elastic waves. The treatment time at high temperatures is brief and administered in sequences of 4 to 7 seconds. In vitro studies on blocks of polyurethane demonstrated melting of the plastic at the focal point. Studies on plastic spheres introduced into the bladder of the pig demonstrated melting of the sphere without any alteration in the tissues in the wave path. Studies of cellular viability of bladder carcinoma cultures demonstrated a significant difference after 48 hours between the non-treated control group and the group of cells submitted to high temperatures. This technique, called Pyrotherapy, should be promising if the preliminary results are confirmed. PMID- 1285391 TI - [The correlation between the level of prostate-specific antigen and prostate gland volume in the early diagnosis of prostatic cancer]. AB - One hundred and eighty six patients (Pts) presenting with either an abnormal per rectum examination (P.R. suggestive of prostatic cancer (P.Ca) (excluding stage T3) or a prostatic specific antigen (P.S.A.) level greater than or equal to 2.5 ng/ml (radioimmunoassay) were submitted to transrectal ultrasonography (T.R.U.) using a 7 MHz transducer. The prostatic volume (Vol.P) was systematically calculated during T.R.U. and correlated with the P.S.A. level. Six systematic multiple ultrasound-guided biopsies (S.M.U.B.) were performed in the 2 prostatic lobes (3 per lobe) regardless of the result of T.R.U. In the 111 patients in whom the S.M.U.B. were negative, a highly significant correlation (p < 0.001) was observed between the serum P.S.A. level (y) and the prostatic volume (Vol.P): y = (4.13 +/- 0.15 Vol.P) +/- 8.43. In the 75 Pts with P.Ca, the P.S.A./Vol.P correlation was significantly different (p < 0.05) from the straight line of regression with the previous standard deviation. A similar difference in correlation (p < 0.05) was observed in the sub-group of 14 Pts with P.Ca despite normal P.R. and T.R.U. These results suggest: 1) that there is a correlation between the Vol.P measured by T.R.U. and the P.S.A. level in patients with negative S.M.U.B. 2) that the absence of correlation is highly suspicious of P.Ca and requires S.M.U.B. 3) that there is a 15% incidence of P.Ca in the sub-group of Pts with normal P.R. and T.R.U. which are only detected by the raised P.S.A. not correlated with the volume of the prostate. PMID- 1285393 TI - [Screening for Down syndrome in the fetus using maternal blood samples]. PMID- 1285394 TI - [Structure and function of ion channels]. PMID- 1285395 TI - [Receptors and mediators in nerve cells]. PMID- 1285396 TI - Differences in the K(+)-channels opened by cromakalim, acetylcholine and substance P in rat aorta and porcine coronary artery. AB - 1. The effects of acetylcholine and substance P on the efflux of 86Rb+ and 42K+ from rat aorta and pig coronary artery, respectively, were compared with those of the K+ channel opening agent, cromakalim. 2. In rat aorta preloaded with 86Rb+ and/or 42K+, acetylcholine produced transient, concentration-dependent increases in the efflux rate coefficients of these tracers (maximum approximately 35%). These effects were abolished by endothelial cell removal. 3. Donor/acceptor experiments with rat aorta suggested that at least some of the efflux of 86Rb+ seen in the presence of acetylcholine was not derived from the endothelium, but came from the smooth muscle itself. 4. Acetylcholine (10 microM)-induced 86Rb+ efflux was reduced by tetraethylammonium (TEA, 10 mM) to 33% and ouabain (300 microM) to 54% of control. Preincubation with Ba2+ (100 microM) did not significantly inhibit acetylcholine-induced efflux. 5. Acetylcholine-induced 42K+/86Rb+ efflux was unaffected by preincubation with glibenclamide (10 microM). In contrast, the 42K+/86Rb+ efflux induced by cromakalim was inhibited by glibenclamide (50 nM) by 50%. 6. Acetylcholine (0.3-10 microM)-induced inhibition of phenylephrine (1 microM)-induced tone was abolished by endothelial cell removal but unaffected by glibenclamide. Cromakalim-induced relaxations were endothelium-independent and were inhibited by glibenclamide in a concentration dependent manner. 7. LG-monomethyl L-arginine (L-NMMA, 250 microM) produced a significant (37 +/- 14%) inhibition of acetylcholine-induced 86Rb+ efflux whereas DG-monomethyl L-arginine was without effect. In the tissue bath L-NMMA inhibited relaxations produced by acetylcholine (0.3-10 microM), but was without effect on responses to cromakalim. 8. In the pig coronary artery, substance P induced an endothelium-dependent efflux of 86Rb+ and 42K+, which was unaffected by preincubation with glibenclamide (10 microM) or L-NMMA (250 microM). 9. The present study shows that acetylcholine and substance P each open K(+)-channels in arterial smooth muscle. However, the insensitivity of the stimulated 86Rb/42K+ efflux to inhibition by glibenclamide suggests that the K(+)-channel opened by these agents is different from the K(+)-channel opened by cromakalim. In addition, the inability of L-NMMA to inhibit fully the acetylcholine- and substance P-stimulated 86Rb+ efflux suggests that in rat aorta and pig coronary artery the endothelium-derived hyperpolarizing factor(s) (EDHF) is different from endothelium-derived relaxing factor (EDRF). PMID- 1285397 TI - Interference of BN 52021, an antagonist of PAF, with different forms of active anaphylaxis in the guinea-pig: importance of the booster injection. AB - 1. BN 52021, an antagonist of platelet activating factor (PAF), was inactive against bronchoconstriction in guinea-pigs sensitized with low amounts of ovalbumin (OA) injected twice, at a 14 day interval and challenged i.v. 7 days later. 2. Serum IgG titers increased for 7 weeks after the booster injection at day 14 and returned to low levels at day 96. 3. Administered by the intratracheal (i.t.) route at 1 mg, BN 52021 failed to inhibit bronchoconstriction induced by the i.t. administration of OA to guinea-pigs tested 7, 28, 56 and 84 days after the booster injection, even when the titers of circulating IgG had declined with time. BN 52021 was also inactive against bronchoconstriction in guinea-pigs boosted at day 98 and tested 7 days later and against contractions and thromboxane (Tx) B2 and histamine release induced by OA-challenged parenchymal lung strips from the boosted guinea-pigs. 4. Sensitized unboosted guinea-pigs displayed reduced IgG serum titers. Used 21 or 70 days after the sensitizing injection, they did develop bronchoconstriction upon the i.t. instillation of OA, which was blocked by BN 52021. The latter also inhibited OA-induced contractions of lung parenchymal strips from these unboosted guinea-pigs. 5. When boosted and non-boosted guinea-pigs received OA i.t. and bronchoalveolar lavage fluid was collected 10 min later, the number of eosinophils increased markedly in boosted, but not in non-boosted guinea-pigs. 6. The booster injection of antigen thus modifies the response of the lung and PAF appears to be relevant for antigen induced bronchoconstriction in unboosted animals, but loses its major role following the booster injection. PMID- 1285398 TI - Selectivity of Ca2+ channel blockers in inhibiting muscular and nerve activities in isolated colon. AB - 1. Potency and efficacy of nifedipine, verapamil and diltiazem and of Bay K 8644 in modifying propulsion and nerve or smooth muscle activities have been compared in the guinea-pig isolated distal colon. Both the neuronal and muscular effects of Ca2+ channel blockers seem to develop at concentrations that are devoid of any significant effect apart from that on Ca2+ channels. 2. Nifedipine, verapamil and diltiazem were all able to impair propulsion, resting and stimulated acetylcholine (ACh) release and smooth muscle contractility in a concentration dependent way. However, some degree of selectivity for neuronal and muscular effects could be observed. Nifedipine was more than 500 fold more potent than verapamil in relaxing musculature but less than twice as potent in reducing ACh release. On the other hand, verapamil was the most efficacious Ca2+ channel blocker tested in inhibiting ACh release, its effects being inversely correlated to the external Ca2+ concentration, and completely abolished by Bay K 8644. 3. By comparing the potencies exhibited by each drug against peristaltic reflex, smooth muscle contractility and ACh release, verapamil proved to be almost as potent in slowing the peristaltic reflex as in reducing ACh release, while nifedipine was about 100 fold more potent against the peristaltic reflex than against ACh release, but nearly equal against the peristaltic reflex and smooth muscle tone. Therefore, interference with cholinergic neurotransmission is likely to play a major role in the antipropulsive effect of verapamil, while peristaltic reflex impairment by nifedipine is likely to be dependent on inhibition of smooth muscle. 4. A facilitatory effect of Bay K 8644 on both the efficiency of the peristaltic reflex and the nonadrenergic, non-cholinergic (NANC) nerve-mediated relaxation could be observed at concentrations at least 10 fold lower than those required to affect ACh release or smooth muscle. 5. It is concluded that the effects of Ca2+ channel blockers on neurotransmitter release may be relevant to their effects on the gastrointestinal motor function. PMID- 1285399 TI - In vitro characterization of prostanoid EP-receptors in the non-pregnant human myometrium. AB - 1. Prostaglandin receptors of the PGE type have been characterized in the non pregnant human myometrium in vitro according to the scheme of Coleman et al. (1984) by use of the agonists PGE2, sulprostone, rioprostil, AY23626, butaprost, misoprostol, 16,16-dimethylprostaglandin E2, enprostil and iloprost, and, the antagonist AH6809. 2. All prostanoids tested were active in non-pregnant human myometrium either as stimulators and/or inhibitors of spontaneous activity or both. Biphasic responses to PGE2 indicate that at least two receptor types of the EP-receptor exist, one mediating relaxation and the other mediating contraction. 3. Further evidence for the EP-receptor mediating excitation and relaxation was provided by the action of the EP2-/EP3-receptor selective prostanoids rioprostil, AY23626 and misoprostol, and the EP1-/EP2-receptor selective agonist 16,16 dimethylprostaglandin E2. 4. Butaprost, an EP2-receptor selective agonist, produced potent inhibition of spontaneous activity in the tissue which was generally longer-lasting than that evoked by the natural prostanoid PGE2. 5. The EP1-/EP3-receptor selective agonist sulprostone and the EP3-receptor agonist enprostil produced potent contractile responses supporting the presence of contractile EP3-receptors in the non-pregnant human myometrium in vitro. 6. The EP1-/IP-receptor selective agonist, iloprost, produced mixed responses in non pregnant human myometrium. The contractile response was inhibited by the EP1 receptor antagonist AH6809. However, responses to the EP1-/EP3-receptor selective agonist sulprostone were unaffected by AH6809 which may indicate that only a small population of EP1-receptors is present. 7. Therefore it would seem that a heterogeneous population of EP-receptors is present in the non-pregnant human myometrium. PMID- 1285400 TI - Blood serotonin (5-HT) level and 24 hrs urinary excretion of 5 hydroxyindoleacetic acid (5-HIAA) in patients with active liver cirrhosis and in patients with hepatic encephalopathy. PMID- 1285401 TI - [Evaluation of the consequences of hepatic artery embolization under experimental conditions]. AB - The experiments were performed in the healthy mongrel dogs aged 5 to 8 years whose body weight ranged from 10-20 kg. Just after the coeliac arteriography the hepatic artery was embolized. The dogs were divided into 2 groups because of the application of two different embolizing materials. Spongostan was used as the embolizing material in group I consisting of 7 dogs. In group II consisting of 5 dogs the embolizing material was absolute ethyl alcohol with urogranic acid. The symptoms of the postembolization syndrome were observed in all dogs after the embolization for 1-5 days. In most dogs the transient increase of the aminotransferase activity was observed while the results of thymol turbidity test and bilirubin levels in serum were not significantly changed. In dogs of group II the clinical picture after the embolization was clearly more severe. The anatomo- and histopathological examinations in dogs after the hepatic artery embolization were carried out. In group I no hepatic changes were found macroscopically. In the histopathological studies of liver the numerous, tiny foci of coagulative necrosis with the resorptive reactions were noticed. In group II multifocal deliquescent necrosis in the liver, numerous, small perivascular and extravascular foci of coagulative-deliquescent necrosis with the inflammatory and the resorptive reactions were noted. PMID- 1285402 TI - Mobilized blood stem cells: immunophenotyping and functional characteristics. AB - High levels of peripheral blood stem cells (PBSC) can be collected from patients with hematopoietic malignancies or solid tumors after high-dose chemotherapy and/or growth factors. Rapid, complete, and durable hematopoietic reconstitution has been observed in patients who have been transplanted with PBSC after conditioning with supralethal myeloablative therapy. We will review the recent data concerning the immunophenotype and functional capacities of mobilized blood stem cells. PBSC seem to be comprised of a mixture of primitive and committed hematopoietic progenitors and are not that different from bone marrow-derived stem cells. PMID- 1285404 TI - The CD34 antigen: structure, biology, and potential clinical applications. AB - The diversity of function of mature circulating blood cells is reflected in their respective complements of cell-surface molecules and receptors. Although monoclonal antibodies have been instrumental in the identification and characterization of many cell-surface molecules on mature hematopoietic cells, the CD34 antigen represents to date, the only molecule, similarly identified, whose expression within the blood system is restricted to a small number of primitive progenitor cells in the bone marrow. Although its precise function remains unknown, the pattern of expression of the CD34 structure suggests that it plays an important role in early hematopoiesis. The availability of CD34 antibodies has greatly aided the development of techniques for the enrichment of primitive progenitor cells for studies of hematopoiesis in vitro. Additionally, the use of CD34 antibodies for the 'positive selection' of hematopoietic stem/progenitor cells represents and alternative strategy to 'negative selection' or purging for the large-scale manipulation of bone marrow cells prior to transplantation. The availability of pure populations of the most primitive hematopoietic progenitor cells may also facilitate the development of genetic techniques for the repair of specific blood cell disorders. In this article, we review the biology of the CD34 molecule and assess some of the roles for CD34 antibodies in immunopathology and for progenitor/stem cell purification in clinical applications. PMID- 1285403 TI - Use of lectins for characterization and purification of human bone marrow cells that express CD34. AB - The binding of lectins to nucleated cells from human bone marrow was studied in a search for markers that can be used to subdivide further immature hemopoietic cells that are characterized by their expression of CD34. Low-density bone marrow cells were indirectly labeled with biotinylated lectins and streptavidin-R phycoerythrin (SA-RPE) together with FITC-labeled monoclonal anti-CD34. Four parameter flow cytometric analysis was then performed and list mode data analyzed. Of the 21 lectins tested, only a few showed differential staining of CD34+ versus CD34- cells. These include soybean agglutinin (SBA) and Ulex europaeus agglutinin I (UE). Lycopersicon esculentum (LE) and Erythrina cristigalli (EC) reacted preferentially with, respectively, CD34+ and CD34- cells, suggesting their usefulness in some method to enrich for CD34+ cells. This possibility was tested by passing cells labeled with biotinylated lectins over a column containing streptavidin-coated beads. CD34+ cells could be enriched > 10 fold by competitive (sugar) elution of LE-labeled cells from the column. Similarly, depletion of biotinylated EC-labeled cells by passage through the streptavidin column enriched CD34+ cells several fold. The results of these studies document the reactivity of a large panel of lectins with subpopulations of nucleated bone marrow cells and indicate that certain lectins could possibly be used for development of cell separation procedures aimed at the selective enrichment of cells that express CD34. PMID- 1285405 TI - Report on the European Workshop on Peripheral Blood Stem Cell Determination and Standardization--Mulhouse, France, February 6-8 and 14-15, 1992. PMID- 1285406 TI - "In the Spirit of Caring": a programmed learning experience with marionettes to poster mental health in the classroom. PMID- 1285407 TI - Role of placenta in women in the circumpolar region in the metabolism of the serum hemoglobin of the fetus. PMID- 1285408 TI - Substance P levels are decreased in lesional skin of atopic dermatitis. AB - There is increasing evidence that neuropeptides (NP) such as substance P (SP) and vasoactive intestinal polypeptide (VIP) are involved in the pathogenesis of atopic dermatitis (AD). Vasoactive intestinal polypeptide levels were found to be significantly elevated in lesional skin of AD as compared to controls. We evaluated by radioimmunoassay the SP content in whole skin homogenates from chronic lichenified lesions of patients with AD. The levels of SP were significantly decreased in lesional skin from AD patients as compared to control skin (0.25 +/- 0.03 vs. 0.97 +/- 0.24 pmol/g tissue, p < 0.01). The diminished SP levels as opposed to increased VIP concentrations could be consistent with different roles of these NP as modulatory agents in the mechanisms associated with AD. PMID- 1285410 TI - Increased expression of ICAM-1, E-selectin, and VCAM-1 by cultured human endothelial cells upon exposure to haptens. AB - Contact allergens induce several accessory signals which promote the activation of antigen-specific T cells. One of these signals is the increased expression of adhesion molecules on antigen-presenting cells and endothelial cells. Epicutaneous application of non-toxic doses of 2,4-dinitrofluorobenzene (DNFB) onto the skin of non-sensitized individuals elicited progressive staining for ICAM-1 on dermal microvascular endothelial cells. To elucidate the question of whether contact allergens can act directly on endothelial cells to elevate their expression of surface structures that bind leukocytes, confluent monolayers of human umbilical vein endothelial cells were incubated with the contact allergens NiSO4, CoSO4 or DNFB. The ICAM-1, E-selectin and HLA-DR expression were quantified by immunofluorescence flow cytometric analysis. Furthermore VCAM-1, E selectin and ICAM-1 transcription were demonstrated by Northern blot hybridization. Constitutive ICAM-1 expression on HUVEC increased similarly to that obtained after LPS (20 micrograms/ml) stimulation after 4 and 24 hours of incubation with 1 or 2 mM NiSO4 or CoSO4, respectively. Pulse-stimulation with 100 or 500 nM DNFB resulted in a modest but significant increase of ICAM-1 positive cells. E-selectin and VCAM-1 were not expressed on untreated HUVEC; 4 to 6 hours exposure to nickel sulfate and LPS resulted in a potent induction of E selectin and VCAM-1 expression. DNFB and PMA had no significant influence on VCAM 1 expression. None of the tested contact allergens was capable of inducing HLA-DR expression on EC at 48 to 72 hours. Enhanced expression of adhesion molecules may be an important early unspecific mechanism for induction and elicitation of a contact dermatitis. PMID- 1285409 TI - Evidence that filopodia outgrowth is a common final pathway for fibroblast growth inhibition in vitro. AB - To identify events associated with fibroblast growth inhibition, the effect of two known inhibitors, interferon-alpha and all-trans retinoic acid, on the growth and surface morphology of cultured fibroblasts was examined. Interferon-alpha administered at seeding reduced both growth rate and saturation density; all trans retinoic acid reduced only saturation density. However, both negative growth modulators were associated with an increase in filopodia outgrowth and an increase in intracellular filamentous actin in a time course corresponding to onset of growth inhibition by these agents. In combination with earlier findings, these data suggested that, regardless of etiology, cultured fibroblast growth restriction is mediated in part by an actin-dependent outgrowth of filopodia that augment intercellular contact. PMID- 1285412 TI - The ELAM-1 ligand sialosyl-Le(X) is present on Langerhans cells isolated from stratified epithelium. AB - In this study we show the expression of the newly identified carbohydrate ligand, sialosyl-Le(X) on Langerhans cells. The receptor for sialosyl-Le(X) is the endothelial leukocyte adhesion molecule-1 (ELAM-1) present on activated endothelial cells. Using flow cytometry, Langerhans cells were selected due to positivity for an antibody against CD1a and low orthogonal light scatter. The CD1a antigen stained by the OKT6 antibody is considered a maturational marker of Langerhans cells in agreement with the specific labeling of dendritic cells in the epithelium only. Double immunostaining (OKT6/anti-sialosyl-Le(X)) using flow cytometry and immunohistochemistry demonstrated that almost all OKT6-positive cells in normal stratified epithelium expressed sialosyl-Le(X). Conversely, by immunohistochemistry of oral epithelium with acute inflammation, additional dendritic cells negative for OKT6 were found to express sialosyl-Le(X). In addition, sialosyl-Le(X)-positive but not OKT6-positive dendritic cells were found in the submucosa. These findings indicate that the carbohydrate antigen sialosyl-Le(X) is expressed earlier than the CD1a antigen in the maturation of the Langerhans cell lineage. Future studies should aim at investigating the importance of adhesion between sialosyl Le(X) and ELAM-1 in epithelial recruitment of Langerhans cells. PMID- 1285413 TI - Immunity, microbial pathogenesis, and immunophilins: finding the keys, now where are the locks? AB - The discovery and clinical use of the immunosuppressants cyclosporin A, FK506, and rapamycin have greatly advanced solid organ and bone marrow transplantation. Though active as antibiotics against a variety of pathogens, their utility has been severely limited by toxicity. Research on the immunophilins, the major binding proteins of these drugs, has given new insights into protein folding and transport as well as mediators of signal transduction in mammalian cells. Microbial immunophilins may also have direct relevance to the intracellular survival of important human pathogens. Defining the mechanisms of enhanced virulence generated by these proteins holds great promise for understanding both the fundamental pathogenesis of these organisms and the immune response generated against them. Such an understanding may provide novel targets for the design of anti-infective agents as well as assist in the development of future immunosuppressives. PMID- 1285411 TI - Diet-induced dermatitis response of hairless rats to systemic treatment with cyclosporin A (Sandimmun), cyclosporin H and FK506. AB - Weaned hairless rats were fed a diet deficient in fat, magnesium and folacin. After approximately 1 week, an erythematous dermatitis developed which was associated with extreme generalized pruritus. Scratching led to excoriations and hemorrhagic crusting. The acute stage (pruritic rash) resolved after several days and was followed by sporadic non-itching relapses. Subsequent to the onset of symptoms, rats were treated orally, once daily for 3 days with CyA, CyH or FK506. The immunosuppressants CyA and FK506 caused a dose-dependent inhibition of symptoms in contrast to CyH. The immediate clinical response was associated with changes in blood histamine, white blood cell counts and histological parameters. Since CyH is known to lack immunosuppressive activity, these results may indicate that the cutaneous changes induced by the nutritional deficiency are associated with immunological abnormalities. The results may also indicate mechanisms influenced by CyA and FK506 but not by CyH; for example, release of chemical mediators from inflammatory cells. PMID- 1285414 TI - [A new tachykinin receptor revealed by substance P analogues in the guinea pig ileum]. AB - [Pro9]SP and septide have been described as selective agonists for the SP receptor (NK-1 type). These two peptides contract with a great efficacy the guinea-pig ileum, but unexpectedly septide was practically devoid of affinity for the NK-1 site labelled by 3H-[Pro9]SP. Like septide, SP analogues like SP-O-CH3, [Apa9-10]SP and [Pro9,10]SP share the same peculiar properties. In addition, the contracting activity of these peptides is not explained by an interaction with NK 2 or NK-3 sites. GR 71,251, a compound which has been described as NK-1 antagonist, was more potent in inhibiting the septide- and the [Apa9-10]SP- than the [Pro9]SP-evoked contracting responses. Altogether, these results suggest that septide, SP-O-CH3, [Apa9-10]SP and [Pro9,10]SP exert their high contracting activity in the guinea-pig ileum by acting on a new type of tachykinin receptor. PMID- 1285415 TI - [Development, during ontogenetic development of gymnotids, of substance p expression in tuberous organs (electroreceptors)]. AB - The evolution of the neuropeptidic expression of Substance P has been investigated with immunohistochemistry in the cutaneous electroreceptors, tuberous organs, during ontogenetic development of Apteronotus leptorhynchus. In the present data, antiSP antiserum has been applied to serial sections of Apteronotus leptorhynchus larvae obtained from several egg layings. Larvae were taken during development from hatching up to one hundred days old. SP immunoreactivity appeared just after hatching, in the epidermal zones which give rise to cutaneous sense organs. Four days after hatching, the tuberous organs are differentiated and immunoreactivity was observed in these organs, in both sensory cells and accessory cells. From day 30 after hatching, there was a regular decrease in the number of tuberous organs showing labelled accessory cells, and one hundred days later only 8% of tuberous organs had immunoreactive accessory cells. The adult accessory cells were no longer labelled with anti-SP antiserum. The results showed that in Apteronotus leptorhynchus, the epidermal structures which give rise to the cutaneous sensory organs were immunoreactive at a very early stage of development; this suggests that SP could have an effect upon their differentiation. PMID- 1285416 TI - Effect of established and putative anxiolytics on extracellular 5-HT and 5-HIAA in the ventral hippocampus of rats during behaviour on the elevated X-maze. AB - One of the proposed mechanisms of action for the anxiolytic effects of the benzodiazepines is via a decrease in central serotonergic neurotransmission. The aim of this study was to combine in vivo microdialysis in the rat with behaviour on the elevated X-maze to determine changes in 5-HT release in the ventral hippocampus with concomitant measurement of behaviour. Twenty minutes exposure to the elevated X-maze resulted in an increase in extracellular 5-HT in the ventral hippocampus with no change in extracellular 5-HIAA. Restricting the rat to either the open or the closed arms produced an increase in extracellular 5-HT, however the increase in 5-HT when restricted to the open arms was not significantly greater than that on the closed arms. Forty minutes pretreatment with diazepam (2.5 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus and had an anxiolytic profile over 5 min and 20 min exposures of the rats to the X-maze. Diazepam had no effect on basal 5-HT levels before exposure to the X-maze but reduced extracellular 5-HT levels when the animal was returned to the holding cage. Forty minutes pretreatment with the .5 HT1A receptor partial agonist ipsapirone (1 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus but did not produce behaviour different from vehicle controls after 5 or 20 min periods on the X maze.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285417 TI - Uremic syndrome revisited: a pathogenetic role for retained endogenous inhibitors of nitric oxide synthesis. PMID- 1285418 TI - New models for the mechanism of transcription elongation and its regulation. PMID- 1285420 TI - The origin of P elements in Drosophila melanogaster. AB - The P family of transposable genetic elements is thought to be a recent addition to the Drosophila melanogaster genome. New evidence suggests that the elements came from another Drosophila species, possibly carried by parasitic mites. The transposition mechanism of P elements involves DNA gap repair which may have facilitated their rapid spread through D. melanogaster worldwide. These results provide new insight into the process of a transposon's invasion into a new species and the potential risk of extinction such an invasion might entail. PMID- 1285419 TI - Structural biology of cell surface interactions. PMID- 1285421 TI - Thy-1, the enigmatic extrovert on the neuronal surface. AB - Thy-1 is a small glycoprotein of 110 amino acids which, folded in the characteristic structure of an immunoglobulin variable domain, are enchored to the plasma membrane via a glycophosphatidylinositol (GPI) tail (Fig. 1). It is a major component of the surface of various cell types, including neurons, at certain stages of their development. These qualities doubtlessly appeal to certain cognoscenti, but it is not clear why they would raise Thy-1 to the status of a favourite molecule. Indeed, few scientists readily admit to having a favourite. We study individual molecules because science is rooted in specific observations; but we do so in order to discover mechanisms of general importance. A molecule's appeal is dependent on its ability to reveal novel aspects of how nature works. Thy-1 has been unusual in this respect. It was the first lymphocyte surface antigen shown to be restricted to a functional subset of lymphocytes (T cells in the mouse), a finding crucial to the development of cellular immunology; it was one of the first cell surface molecules to be sequenced and indicated the importance of immunoglobulin domains and GPI anchors as structural motifs; it has been pivotal in studies demonstrating that GPI-anchored molecules are able to signal across the membrane they do not span. Thy-1 has revealed this much, however, with the charm of an adroit stripper: it has always promised glimpses of things more exciting than that displayed. In particular, the function of this molecule has never emerged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285422 TI - Fetuin--an old friend revisited. AB - Bovine fetuin, the first fetal protein to be described, has recently been shown to be a species homologue of a well known human plasma protein--alpha 2HS glycoprotein (alpha 2HS). The fetuins are now known to be members of the cystatin superfamily. The structural properties of the six fetuins that have been fully sequenced are compared. Despite the structural homology of these proteins, their described properties in the literature make them appear to be quite different. The diverse in vitro properties claimed for fetuin/alpha 2HS are reviewed. In vivo, fetuins are involved in the acute phase response. In development, in all species studied so far, fetuins are present in a specific cell population that forms the developing neocortex. The possible functional significance of this distribution is discussed. PMID- 1285423 TI - The selectin family of carbohydrate-binding proteins: structure and importance of carbohydrate ligands for cell adhesion. AB - Protein-carbohydrate interactions have been found to be important in many steps in lymphocyte recirculation and inflammatory responses. A family of carbohydrate binding proteins or lectins, termed selectins, has been discovered and shown to be involved directly in these processes. The three known selectins, termed L-, E- and P-selectins, have domains homologous to other Ca(2+)-dependent (C-type) lectins. L-selectin is expressed constitutively on lymphocytes, E-selectin is expressed by activated endothelial cells, and P-selectin is expressed by activated platelets and endothelial cells. Here, we review the nature of the carbohydrate determinants in tissues recognized by these selectins. The expression of specific sialylated, fucosylated and sulfated carbohydrates in activated endothelium and high endothelial venules promotes interactions with L selectin on leukocyte surfaces. In contrast, E- and P-selectins recognize specific carbohydrate determinants related to sialyl Le(x) antigen on neutrophil and monocyte surfaces. The discovery of the selectins has generated excitement among glycoconjugate researchers that other carbohydrate-binding proteins and their cognate ligands will be found to function in regulating many types of cellular interactions. PMID- 1285424 TI - Myelin P0-protein, more than just a structural protein? AB - The protein P0 has long been proposed to be responsible for the compact nature of peripheral myelin through interactions of both its extracellular and cytoplasmic domains. Recent studies support such a role for P0's extracellular region while more precise mapping of its adhesive domains are ongoing. As P0 is a member of the immunoglobulin gene superfamily and perhaps bears the closest similarity to the ancestral molecule of this whole family, these studies may also have more general implications for adhesive interactions. In addition, although long believed to be purely an inert, structural molecule, P0 has been reported to promote neurite outgrowth, which suggests a more dynamic role for this interesting molecule. PMID- 1285425 TI - [Vibrio cholerae can be encountered even at home]. PMID- 1285426 TI - [Serotonin metabolism in the framework of aggression and violence]. PMID- 1285427 TI - [Aphasia in adults]. PMID- 1285428 TI - [The use of botulinum toxin in neurology]. PMID- 1285429 TI - [Desmoplastic tumor in the abdominal cavity--"new" small-cell tumor in young subjects]. PMID- 1285430 TI - [1991 Nobel Prize to scientists studying ion channels]. PMID- 1285431 TI - [How harmful are anti-interferon antibodies?]. PMID- 1285432 TI - [Urinary retention]. PMID- 1285433 TI - [Is the Finnish heritage of disease disappearing?]. PMID- 1285435 TI - Comparison of intensities between doubly charged ions [M + 2H]2+ and singly charged ions [M + H]+ of gramicidin S by electrospray mass spectrometry. AB - The reason why the intensity of doubly charged ions [M + 2H]2+ of gramicidin S is higher than that of singly charged ions [M + H]+ in electrospray is investigated by ion evaporation theory. As a result of comparison between the total free energies of extracting [M + 2H]2+ and [M + H]+ from a charged droplet to infinity, it is found that the total free energy of [M + 2H]2+ is estimated to be lower than that of [M + H]+. This clearly supports the experimental result. In addition, the importance of the electrostatic contribution in electrospray is demonstrated by showing the result that the total free energy of [M + 2H]2+ without electrostatic contribution is higher than that of [M + H]+. PMID- 1285434 TI - The effect of galanin on growth hormone-releasing factor and somatostatin release from median eminence fragments in vitro. AB - Galanin has been reported to stimulate secretion of GH in humans and rats. Thus, to investigate whether the effect of galanin on GH release is the result of either a stimulation of GH-releasing factor (GRF) and/or an inhibition of somatostatin (SRIF) release, we have evaluated the action of galanin on the release of SRIF and GRF from median eminence (ME) fragments in vitro. The MEs from adult male rats were incubated in Krebs-Ringer bicarbonate-glucose buffer, pH 7.4, at 37 degrees C, in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. Medium was discarded and replaced by medium containing various concentrations of galanin (10(-10)-10(-7) M). Galanin stimulated SRIF and GRF release in a dose-related manner. This effect was significant at concentrations varying from 10(-8) to 10(-7) M. To determine the mechanism by which galanin stimulated SRIF and GRF release, MEs were incubated with pimozide (dopaminergic blocker), phentolamine (alpha-adrenergic blocker) or naloxone (opioid blocker), at concentrations of 10(-6) M, and the effect of galanin was then evaluated. Phentolamine and naloxone did not alter the stimulatory effect of galanin, but when galanin was tested with pimozide, the galanin-induced release of SRIF and GRF was blocked. To determine whether the effect of galanin is mediated through D 1 and/or D-2 dopamine receptors, selective antagonists of D-1 (SCH 23390) and D-2 receptors (domperidone) were used (10(-7) M) in the presence of galanin (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285436 TI - Differential inhibition of the activities of reverse transcriptase and various cellular DNA polymerases by a traditional Kampo drug, sho-saiko-to. AB - A traditional Kampo drug, Sho-saiko-to, composed of several herb extracts, differentially inhibited the activities of reverse transcriptase and human cellular DNA polymerase alpha and beta. Reverse transcriptases from murine leukemia virus and human immunodeficiency virus were inhibited by over 80% and 50%, respectively, in the presence of 100 micrograms/ml Sho-saiko-to, whereas DNA polymerase alpha was much less sensitive to inhibition by this drug than were the reverse transcriptases. DNA polymerase gamma was not inhibited by this drug at concentrations of up to 500 micrograms/ml. Only DNA polymerase beta was moderately inhibited by Sho-saiko-to. Thus, it has been shown that the inhibition by Sho-saiko-to is relatively specific for reverse transcriptase and that the drug contains as yet unidentified inhibitory substance(s) for reverse transcriptase. PMID- 1285437 TI - Tropical health and quarantine notes. PMID- 1285438 TI - Nonradioactive in situ hybridization with digoxigenin. PMID- 1285439 TI - Stretch-sensitive ion channels: an update. PMID- 1285440 TI - Amino acid receptor channels in taste cells. PMID- 1285441 TI - The diversity of bitter taste signal transduction mechanisms. PMID- 1285442 TI - The role of calcium in hair cell transduction. PMID- 1285443 TI - The utility of CD20 and CD43 in subclassification of low-grade B-cell lymphoma on paraffin sections. AB - To identify phenotypic differences among the low-grade lympho-proliferative disorders in paraffin-embedded tissue, we studied 49 cases. All 22 follicular small cleaved cell lymphomas (FSC) were CD43 negative and CD20 positive. In contrast, of 20 small lymphocytic lymphomas (SL), 90% were CD20 positive, 85% were CD43 positive, and 75% were positive for both. Of three lymphomas of intermediate differentiation (IDL), two were CD20 positive and two were CD43 positive. All four monocytoid B-cell lymphomas were positive for CD20 and 50% (two cases) were positive for CD43. Some 86% of 14 chronic lymphocytic leukemias (CLL) (on cytospins) were positive for CD43; all nine of the CLL studied for CD20 were positive and 89% (8/9) expressed both antibodies CD5 expression (on frozen sections or cytospin preparations) was compared to CD43 in 21 cases of SL and CLL. Some 77% were positive for both CD5 and CD20. All seven of the CD5-positive SL also expressed CD43. The antibody MT2 was also examined with the following results: FSC, 16/20 (80%) positive; SL, 18/19 (94%) positive; MBC, 3/3 positive; and ILL, 2/3 positive. All 56 cases tested were CD45RO (UCHL1) negative. We conclude that CD43 is expressed on most cases of low-grade lymphoproliferative disorders with the exception of FSC. Its pattern of expression seems similar to CD5; however, unlike CD5, CD43 can be studied in formalin-fixed tissue. MT2 is not helpful in distinguishing among these lesions. PMID- 1285444 TI - Modification of tumor ploidy level via the choice of tissue taken as diploid reference in the digital cell image analysis of Feulgen-stained nuclei. AB - We studied the influence of five cell nucleus populations taken as diploid standards with respect to the normalization of a human breast carcinoma. Four normal human tissues (lymphocytes, thyroid, liver, and bladder specimens) were taken as external standards, while the normal breast cells "contaminating" the tumor were taken as the internal diploid standard. Nuclear size and nuclear DNA assessments were performed by means of a cell image processor computing the parameters on Feulgen-stained nuclei from fresh imprint smears fixed in an ethanol-formalin-acetic acid mixture. Our results demonstrate that the choice of normal tissue as the diploid standard markedly influences the ploidy level of breast carcinoma. Normalization according to the lymphocytes led to our obtaining a major hyposextaploid G0-G1 DNA peak in the breast cancer. Using thyroid and liver cells as a standard, we obtained a major pentaploid and sextaploid G0-G1 peak, respectively. Using bladder cells or the normal contaminating breast cells within the tumor, we obtained a major tetraploid G0-G1 peak. Finally, the normalization of the normal bladder cells against the liver cells led to our obtaining a near triploid bladder specimen. The reverse feature was also observed, e.g., the obtaining of biologically nonsensical hypodiploid liver cells after normalization against the normal bladder cells. Such postnormalization variations in ploidy level depend upon the mean nuclear size and the mean nuclear DNA content of the normal tissue taken as diploid standard.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285445 TI - Correspondence re: Shah IA, Schlageter M-O, Stinnet P, Lechago J: Cytokeratin immunohistochemistry as a diagnostic tool for distinguishing malignant from benign epithelial lesions of the prostate. Mod Pathol 4:220, 1991. PMID- 1285446 TI - [Rhythmic pneumatic compression of the limb as a contributing element of postoperative deep vein thromboembolism prophylaxis in patients after orthopedic surgery]. AB - A combined prophylaxis against postoperative deep venous thrombosis comprising of sequential pneumatic limb compression using RMP I/K apparatus and lysine or dextran 70.000 administration was of applied in 34 patients after total hip arthroplasty. In 14 cases lysine was the drug, dextran was used in remaining ones. Prophylaxis was evaluated by impedance plethysmography. No case of postoperative deep venous thrombosis was reported. PMID- 1285447 TI - Donizetti and the music of mental derangement: Anna Bolena, Lucia di Lammermoor, and the composer's neurobiological illness. AB - The composer Gaetano Donizetti, who died in a state of mental derangement due to neurosyphilis, created some of opera's greatest scenes of psychosis. His letters reveal the clinical progression of his neurobiological illness, which was confirmed by autopsy. One can hypothesize that the composer's brain disease, which led to his psychosis and death, may have had an influence on his ability to create the powerful and unforgettable scenes of psychosis in his operas. In Anna Bolena, he captured in musical and dramatic terms Anne Boleyn's historically corroborated mental disorder during her imprisonment in the Tower of London. Sixteen years after having composed Anna Bolena, Donizetti himself would be locked up, against his will, in a mental institution. In Lucia di Lammermoor, Donizetti portrayed a girl given to hallucinations who, in her unforgettable "mad" scene, comes on stage, a pathetic embodiment of a human being in the throes of psychosis. Thirteen years after Lucia's premiere, Donizetti would die, psychotic and paralyzed, of untreated neurosyphilis. Studying Donizetti's neurosyphilis and the portrayals of psychosis in his operas can help one to appreciate the pain of human beings trapped in the prison of a brain subjected to the devastation of mental derangement. PMID- 1285448 TI - Obstetrical events that shaped Western European history. AB - Taking into account that marriage, the family as a social unit, and concepts of legitimacy developed to ensure the devolution of property and that, when these concepts apply in a society based on hierarchically organized monarchies, they also involve the devolution of power, this essay furnishes examples of dislocations in such devolutions, in terms of familiar incidents in western European history. That Jane Seymour died in childbirth but her son Edward VI survived long enough to ensure the stability of the Church of England is the first example. The infertility of Mary Tudor, when married to Philip II of Spain, prevented the formation of an Anglo-Spanish dynasty that would have been Roman Catholic is the second example of such a dislocation. Likewise, the infertility of Charles II's wife, Catherine of Braganza, led to the succession of James II, a practicing Roman Catholic, whose attempts to undermine the Church of England led to the Glorious Revolution of 1788 and the preservation of English Protestantism. Another example is the death in 1817 of Princess Charlotte, in childbirth, which led to the scramble of George III's aging sons to marry and beget an heir to the throne. The only success led to the birth of the future Queen Victoria, whose dynastic competence remains unquestionable, but who herself had some passing involvement with obstetrical developments. Finally, the delivery of Kaiser Wilhelm II, who sustained a brachial plexus injury that produced Erb's palsy of the left arm, is considered, and the question of intrapartum fetal hypoxia is raised as a hypothesis, in addition to the mechanical trauma and its effect on his personality. PMID- 1285449 TI - Politics and pellagra: the epidemic of pellagra in the U.S. in the early twentieth century. AB - The epidemic of pellagra in the first half of this century at its peak produced at least 250,000 cases and caused 7,000 deaths a year for several decades in 15 southern states. It also filled hospital wards in other states, which had a similar incidence but refused to report their cases. Political influences interfered, not only with surveillance of the disease, but also in its study, recognition of its cause, and the institution of preventive measures when they became known. Politicians and the general public felt that it was more acceptable for pellagra to be infectious than for it to be a form of malnutrition, a result of poverty and thus an embarrassing social problem. Retrospectively, a change in the method of milling cornmeal, degermination, which began shortly after 1900, probably accounted for the appearance of the epidemic; such a process was suggested at the time, but the suggestion was ignored. PMID- 1285450 TI - The discovery of the body: human dissection and its cultural contexts in ancient Greece. AB - In the first half of the third century B.C, two Greeks, Herophilus of Chalcedon and his younger contemporary Erasistratus of Ceos, became the first and last ancient scientists to perform systematic dissections of human cadavers. In all probability, they also conducted vivisections of condemned criminals. Their anatomical and physiological discoveries were extraordinary. The uniqueness of these events presents an intriguing historical puzzle. Animals had been dissected by Aristotle in the preceding century (and partly dissected by other Greeks in earlier centuries), and, later, Galen (second century A.D.) and others again systematically dissected numerous animals. But no ancient scientists ever seem to have resumed systematic human dissection. This paper explores, first, the cultural factors--including traditional Greek attitudes to the corpse and to the skin, also as manifested in Greek sacred laws--that may have prevented systematic human dissection during almost all of Greek antiquity, from the Pre-Socratic philosopher-scientists of the sixth and fifth centuries B.C. to distinguished Greek physicians of the later Roman Empire. Second, the exceptional constellation of cultural, political, and social circumstances in early Alexandria that might have emboldened Herophilus to overcome the pressures of cultural traditions and to initiate systematic human dissection, is analyzed. Finally, the paper explores possible reasons for the mysteriously abrupt disappearance of systematic human dissection from Greek science after the death of Erasistratus and Herophilus. PMID- 1285451 TI - On medicine and politics. AB - This paper explores the relationship between medicine and politics, between medical management of the human body and governmental management of the body politic. It argues that the increasing complexity both of society and of governmental administration of society in the modern age has made it impossible completely to separate medicine from politics. It demonstrates that, along with great potential for social benefit, "medico-politics" brought with it great danger; much harm has been done purportedly to heal the body politic. The paper concludes by suggesting a way for physicians to minimize this danger. PMID- 1285452 TI - Medicine in Mississippi. AB - Adequate health care represents an issue that has always troubled rural America. From the earliest days of this country, affordable and quality health care has often been harder to find for those who those to live on the farm or in a small town or any place off the beaten path than it has for residents in urban areas. The State of Mississippi has undertaken an intensive program to widen access to health care--and, especially, to preventive health measures--by utilizing fully all available financial resources, including private foundations, by encouraging increased cooperation from our physicians and hospitals in caring for patients insured by Medicaid, and by involving the community in emphasizing the use of health care practitioners in delivering inexpensive but effective support to our rural population. PMID- 1285453 TI - [Adverse drug effects and the liver]. PMID- 1285454 TI - [Idiopathic chronic inflammatory bowel diseases]. PMID- 1285455 TI - [Sleep apnea. Pathophysiology, diagnosis, therapy]. PMID- 1285456 TI - [Roentgenologic loosening after endoprosthesis implantation in the hip joint- early and late signs]. PMID- 1285457 TI - [Surveillance of the incidence of diabetes mellitus in a rural area of Mecklenburg-Vorpommern]. PMID- 1285458 TI - [Analysis of studies of ambulatory morbidity in Germany with special reference to disease classification]. PMID- 1285459 TI - [Case from general practice (4): a stuporous elderly female]. PMID- 1285460 TI - [Johann Philipp Hagen (1734-1792). Comments on his career as a Berlin obstetrician and teacher of midwifery]. PMID- 1285461 TI - [Possibilities and limits of medical graphology. Determination of current status and perspectives (I)]. AB - As is generally known, the writing movement reacts in a sensitive manner to numerous diseases, medications, stimulants and environmental poisons, as well as to psychic and physical influences. This reaction can occur quite early in the process. Therefore, laboratory data and the physical examination can be supplemented by the handwriting. The graphological analysis is particularly helpful in the following ways: early diagnosis, documenting the course of the disease, evaluating treatment, psychological relationships as well as the problems of old age. This review, presented in three parts, intends to demonstrate to the physician simple and time-saving possibilities, as well as analytical methods, that are most likely to promise success. This needs to be done by a competent graphologist.-Prejudices against graphological methods and exaggerated expectations will be reduced if proper information is presented. PMID- 1285463 TI - [Conventional roentgen functional diagnosis--videodensitometry. 4. Conventional roentgen videodensitometry exemplified with peri-cardiac vessels]. AB - It is possible to record movement-parameters by means of roentgen videodensitometry of the great central vessels as well the pulmonary artery as the thoracic aorta visible in fluoroscopic image (provided by videorecorder). We could noninvasively measure pre-ejection periods (PEP) for the right heart (PEP f) as well for the left heart (PEP g) by synchronous electrocardiography for each cardiac action and for each examination process. It is important to form a quotient between PEP f and PEP g in the individual case. First findings in patients with cardiac septal defects (with and without right heart block and pulmonary hypertension) show characteristic quotients and figures of the curves. In cases with electrocardiographic left heart block the elongated PEP g can be stated in graduated form. Further investigations on the mechanic interaction between the right and left heart, especially in cases of disorders in the heart conduction system, might be of interest. PMID- 1285462 TI - [What does general practice hypertension mean?]. AB - White coat hypertension means an isolated blood pressure elevation during conventional measurement in the doctor's office, while blood pressure is in the normal range outside the office over 24 hrs. The incidence is about 20-25% of all "hypertensives" identified in the office. Patients with white coat hypertension show no increased blood pressure variability outside the office, and they do not seem to be more anxious regarding psychological testing as compared with hypertensives. The white coat effect is very specific for the situation in the doctors office. The effect is more pronounced in younger and female patients. However, also in isolated systolic hypertension in the elderly the white coat effect is present to a substantial amount. Under dynamic exercise there is no different hemodynamic response in patients with white coat hypertension as compared with normotensives. Differences are however observed with regard to posture and under isometric exercise. So far, white coat hypertension seems to be a benign and harmless condition not related to an increased cardiovascular risk, which must not be treated. PMID- 1285464 TI - [Postmenopausal osteoporosis from the viewpoint of the gynecologist]. AB - Prophylaxis of postmenopausal osteoporosis is of major importance if estrogen replacement therapy is considered. Assessment of clinical symptoms, (standardized) x-ray analysis, and bone densitometry contribute to the final diagnosis. Incidence of osteoporotic fractures is rising due to alterations in life style and dietary habits. One out of three to four women eventually suffer from osteoporosis in the European countries, United States and Japan. Prevention of postmenopausal osteoporosis is achieved by adequate estrogen replacement therapy carried out for years, maintaining peripheral estradiol concentrations of 220 pmol/l. Doses of 2 mg estradiol or 0.625 mg of conjugated estrogen or 50-100 micrograms percutaneous estradiol/day are equally effective for prevention. The additional administration of a progestogen may be of specific value to increase the antiresorptive effect of estrogens. We distinguish between estrogen replacement in a cyclic or continuous way combined with a sequential or continuous progestogen in women with intact uterus. PMID- 1285465 TI - [Mining medicine in the 18th century. On the 250th anniversary of the birthday of Ignaz von Born (1742-1791)]. AB - Ignaz von Born (1742-1791) improved several technical and methodical approaches to mining and was thus instrumental in creating the prerequisites for reducing certain professional miner's diseases. Among these diseases, lead or saturnine poisoning (colica saturnina) caused by lead monoxide PbO, also known as litharge, was much dreaded (a 17th-century physician from Goslar wrote a treatise on "Lithargyrii fumo noxio morbifico, vulgo dicto 'pit cat'"); a miner's disease associated with phthisis and pareses of a then unknown etiology; and in some cases even with hookworm disease that was much later recognised as yet another professional disease of miners. During this era a new professional image of a mining engineering physician developed, with several of these doctors trying to go beyond merely curative measures: they aimed at achieving meaningful prevention that involved standard measures and behavioural patterns on the one hand and improvements in the professional mining procedure on the other. PMID- 1285466 TI - [Failure to lend aid by the physician]. PMID- 1285467 TI - [Diagnosis of brain death]. AB - From the medical, the juridical as well as the theological point of view brain death represents the death of an individual. According to the German Chamber of Physicians, acute brain damage with coma, absence of all brainstem reflexes and apnoe allows the diagnosis of cerebral death, if repetition of the physical examination after distinct time intervals documents the irreversibility of this state. Additional investigations such as EEG, evoked potentials (BAEP), transcranial doppler sonography, brain scintigraphy or cerebral angiography allow to shorten this period if electrocortical silence, absence of waves 3-5 of BAEP or the cessation of cerebral perfusion has been proven. Strict observation of these criteria is mandatory for the diagnosis of brain death. PMID- 1285468 TI - [Management of the organ donor]. AB - Brain death is associated with loss of hypothalamic, pituitary and brain stem function resulting in apnea, bradycardia and hypotension, poikilothermia, and diabetes insipidus. In order to preserve body functions mechanical ventilation is continued with the aim to maintain an arterial partial pressure of oxygen of more than 100 mmHg. Previous fluid restrictions and the application of diuretics during the treatment of high intracranial pressure frequently result in dehydration. Progressive vasodilation may induce severe hypotension and fluid replacement with cristalloids and if necessary colloids may be called for until the central venous pressure reaches 10 cm H2O. Continuous substitution of potassium and the use of hypotonic solutions such as glucose 5% may avoid hypokalaemia and hypernatraemia, respectively. Inotropic support with dopamine (5 10 micrograms/kg.min) or adrenaline (0.01-0.1 micrograms/kg.min) may be needed to maintain normal mean arterial blood pressure (65 mmHg). Polyuria (5000 ml/24 h) can be treated by continuous intravenous infusion of antidiuretic hormone (0.5-2 10 U/h). Hypothermia must be prevented by warming all fluids (37 degrees C) and covering the patient with heat saving blankets. PMID- 1285469 TI - [Organ preservation]. AB - For organ preservation in Europe the Euro-Collins-, UW- and HTK-solution are preferred. While the HTK-solution is mainly used for heart preservation, the UW solution has shown its advantages for longterm preservation of kidney, liver and pancreas. With regard to renal preservation the HTK-solution provides a higher buffer capacity. According to experimental and theroretical considerations the content of glucose in the Euro-Collins-solution does not seem to correspond to the current state of knowledge. In order to obtain a sufficient primary function renoprotective measurements have proven their efficacy, in addition to an optimal method of organ preservation. Especially in case of suboptimal donors the preservation time should be kept as short as possible. PMID- 1285470 TI - [Immunosuppression after organ transplantation]. AB - Immunosuppression after organ transplantation is based on pharmacologic interventions using steroids, azathioprin, sandimmun and anti-T-cell-globulins. During the induction-period the use of a high-dose combination-therapy guaranties a low incidence of rejection episodes. However infective complications may predominate. In the long-term phase the results of different immunosuppressive protocols are similar in respect to patient- and graft survival. This circumstance promotes the possibility to perform an individualised immunosuppression, which compiles to the personal demands of the graft recipient. PMID- 1285471 TI - [Organ transplantation in childhood]. AB - Organ transplantation in children has to consider the development of the children. One limitation is the organ size of orthotopic transplanted organs as liver, heart and lung. The activation of unspecific immune response in the pediatric recipients is a risk of rejection episodes especially in infants. The experiences of the Medical School Hannover with 203 pediatric renal recipients and with 117 pediatric liver recipients are reported. Congenital disorders with chronic organ insufficiency frequently lead to growth retardation and cardiovascular complications already before transplantation and determine the long term outcome especially in renal transplantation. PMID- 1285472 TI - [Conservative therapy of liver failure]. AB - Hepatic failure is characterized by decreasing liver function involving synthesis, regulation and detoxification. In most cases, acute liver failure results from acute viral hepatitis. Furthermore, intoxications or metabolic decompensation can cause fulminant hepatic failure. Chronic liver failure is defined as progressive decline in liver function in previously existing liver disease, mostly liver cirrhosis. Clinical manifestation of both acute and chronic hepatic failure is determined by hepatic encephalopathy and severe disturbance of the hemostatic system. Causal therapy does not exist; the inducing agent or reason should be eliminated. The major supportive strategy comprises removal of toxic metabolites from the intestine and stabilization of the hemostatic system. As prognosis of both acute and chronic liver failure is very poor, orthotopic liver transplantation represents the ultima ratio therapy. PMID- 1285473 TI - [Indications and results of liver transplantation]. AB - More than 20,000 human liver transplantations have been performed world-wide. The procedure has become universally accepted by hepatologists and applied most broadly for numerous indications in end-stage liver disease. Most common indications for transplantation are benign liver diseases, leading to cirrhosis and/or liver failure. In non-resectable tumor stages liver transplantations have been less frequently performed. The main problem remains to define the "best timing" for the operation. The disease stage will influence the incidence of perioperative complications, postoperative mortality and survival after transplantation. Liver transplantation should be considered, before chronic liver disease reaches its final stage and extra-hepatic liver-related organ complications determine the course. "Ultima ratio" decisions in very late disease stages will leave the patient with only a small chance of surviving. High tumor recurrence rates and inferior survival figures after liver transplantation in malignant liver diseases necessitate a restrictive indication policy in such patients. Probably neoadjuvant chemotherapy in conjunction with liver transplantation will expand the therapeutic modalities in unresectable situations. PMID- 1285474 TI - [Experimental and clinical islets transplantation. Current status]. AB - 25 years have passed since the first enzymatic isolation of islets of Langerhans from the rat pancreas. During this period of time, it could be demonstrated that transplantation of syngeneic islets intraportally into streptozoticin-treated diabetic recipients (rat, mouse) does not only guarantee long term normoglycemia but inhibits also typical late complications of the disease. Allogeneic islets, however, exhibit strong immunogenicity (rejection within a few days) which can be overcome by various immunomodulating in vitro measures of the islets before transplantation. Isolated islets have been successfully transplanted also in larger animals as dogs and pigs, when transplanted in an autologous or allogeneic system. In human diabetes the success rate of islet transplantation up to now is low and cannot be compared with the results in experimental diabetes. The reasons are manyfold: islet damage due to long ischemia time, low number of islets, low purity, lack of diagnostic markers which indicate rejection, autoimmune destruction. The fact that in the meantime a few patients remain insulin independent after a single islet transplant with the maximum of 2 years indicates however that this method in principle may serve as a tool for the treatment of diabetes. This is underlined by several advantages compared to pancreatic organ transplantation as low risk of the procedure for the recipient and the possibility of repeated transplantation. In addition, in the future xenotransplantation of (porcine) islets might be feasible. PMID- 1285475 TI - [Pancreas transplantation]. AB - The results of pancreatic transplantation improved markedly during the last years. Transplantation of the pancreas together with the kidney is the most common treatment of Type I-diabetic patients. At present different surgical techniques are used for the handling of the exocrine secretion of the gland. However, each technique has its own advantages and disadvantages. A successful pancreatic transplantation provides a normal glucose metabolism in the majority of the patients. This leads to an improvement of the peripheral and autonomic neuropathy. Clinical observations suggest a beneficial effect on diabetic retinopathy and peripheral microcirculation. More long-term-results are mandatory to assess the preventive effect of pancreatic transplantation on the development of late diabetic complications. Timing of pancreatic transplantation has a major influence on the course of secondary complications. There is no need for further dietary restrictions or exogenous insulin replacement, so that a better quality of life can be achieved. PMID- 1285476 TI - [Heart transplantation--indications and results]. AB - Heart transplantation has become a standard procedure in the treatment for irreversible heart failure. Criteria for both recipients and donors have been extended. One year survival now reaches 81%. In the immediate postoperative course patients are endangered by infection. In the long-term course coronary artery disease of the transplanted heart becomes the most serious problem. Alteration of liver and kidney function due to chronic medication as well as malignancies and hypertension also occur. In case of chronic transplant failure retransplantation may be indicated. Acute cardiac failure before transplantation nowerdays can be treated by mechanical circulatory assist devices. PMID- 1285478 TI - [Corneal transplantation]. AB - In contrast to organ transplantations corneal grafts are tissue transplantations with the advantage of a minority of immune stimulating cells. The incidence of allograft rejections is greater in penetrating grafts than in lamellar grafts because of endothelial immune reactions. The decompensation of the graft is caused by the damage of the endothelial layer. The influence of HLA-A, -B and -DR matching is proven in case of vascularised cornea or of repeated perforating keratoplasty. The introduction of the immunosuppressive therapy with Ciclosporin A was successful in maintaining a clear graft. PMID- 1285477 TI - [Lung transplantation]. AB - In the past 10 years, three different types of lung transplantation were introduced into clinical practice, the combined transplantation of the heart and both lungs (HLTx), unilateral single lung transplantation (SLTx), and bilateral sequential lung transplantation (DLTx). At present, the indications for the various procedures have not been ultimately defined. Through 1991, a total of about 1,100 HLTx, 460 SLTx, and 160 DLTx was performed worldwide. One- und 3-year survival rates amount to 75-60% resp. in HLTx, to 80-70% resp. in SLTx, and to 70 60% resp. in DLTx. In our own experience with 24 HLTx, 32 SLTx, and 18 DLTx patients, global survival rates at one and 3 years are 85 and 80%, resp. The vast majority of surviving patients is able to lead a near normal life both physically and socially. PMID- 1285479 TI - [Bone marrow transplantation. Overview and personal results]. AB - Main indications for allogeneic bone marrow transplantation are severe aplastic anemia, severe combined immunodeficiency, acute leukemia and chronic myeloid leukemia. In standard risk situations survival rates are 50 to 80%. The probability of disease-free survival after bone marrow transplantation is depending on the stage of disease. If possible bone marrow transplantation should be performed early, not in advanced disease when conventional measures failed. Main problems are therapy-related organ toxicity, rejection, graft-versus-host disease and a long lasting risk of infection. Usually histocompatible relatives of the patients are selected as marrow donors. Bone marrow transplantation using unrelated donors is under investigation. Autologous transplantations with cryopreserved marrow are performed in acute leukemia, malignant lymphomas and some solid tumors, but prospective studies comparing transplantation and conventional therapeutic procedures are still missing. PMID- 1285480 TI - [The gynecologist and hysterectomy]. AB - Often it is postulated by mass media that too much hysterectomies would be performed by gynaecologists. Hysterectomy is today a relatively safe routine intervention. This may tempt to a generous indication. Elective hysterectomy has been looked at critically. Two factors play an important role, firstly the position of the women to her uterus, i. e. how does the women settle down her fertility in her life and secondly the position of the gynaecologist, which will be transmitted from him to the patient cousciously or instinctively. Then our position to alternative methods like endometrial ablation by hysteroscopic laser coagulation or laser assisted or pelviscopic hysterectomies has been demonstrated. PMID- 1285481 TI - [Subjective complaints and hormonal reactions in the first 6 weeks after hysterectomy]. AB - Hormone profiles (estradiol, testosterone, FSH, LH) and typical estradiol deficiency phenomena were investigated prospectively in the first 6 weeks after hysterectomy (n = 50) and after additional bilateral adnexectomy (n = 17). In the second group estradiol was replaced transdermally from the 2nd postoperative day (estradiol patch, 0.05 mg daily). In the 1st group 34% of patients showed a significant decrease in estradiol, 28% of patients a significant decrease in testosterone on the 3rd postoperative day which was no longer demonstrable after 6 weeks. In the second group no decrease in hormone levels was found. So the estradiol patch can replace estradiol to a sufficient degree and in particular physiologically even after bilateral oophorectomy Subjective complaints improved in both groups. Psychosomatic influence also seems to be of importance. PMID- 1285482 TI - [Secretion of hCG by mononuclear cells--a specific and essential reaction in pregnancy?]. AB - Mononuclear cells in peripheral blood secrete immunoreactive hCG (ir-hCG) when they are stimulated in in-vitro culture with the proteinkinase C - activator phorbol-myristat-acetate (TPA). We examined the ir-hCG secretion in 61 fertile and 191 pregnant women and 38 men. Mononuclear cells of pregnant women secrete after TPA stimulation significantly more ir-hCG than mononuclear cells on non pregnant but fertile women. This effect can be detected as early as 23rd days of a menstrual cycle which is accompanied by conception and persisted over the entire duration of a pregnancy. Maximal effects were observed in the 7th to 19th and 30th to 34th weeks of pregnancy. An artefact caused by adhesive serum-hCG could be excluded. The elevated potential of the mononuclear cells to be stimulated remained intact for about 14 days after termination of a normal pregnancy in the first trimester. An ir-hCG secretion similar to that seen in nonpregnant women was found in patients with early abortion. The possible physiological importance of the in-vivo secretion of beta-HCG during pregnancy is discussed. PMID- 1285483 TI - [The limits of hormone substitution in pollutant exposure and fertility disorders]. AB - Heavy metals and chloro-organic compounds can influence female fertility at every phase of reproduction. They may induce hormonal disorders, preventing ovulations and pregnancies. They can also result in abortions and fetal malformations. For this reason, the urinary excretion of heavy metals was measured after oral load with the chelating agent dimercaptopropanesulfonate (Dimaval) in women with hormonal irregularities. In addition, blood was examined for various polychlorinated compounds (polychlorinated biphenyls - PCB -, hexachlorocyclohexane - HCH -, pentachlorophenole - PCP -, hexachlorobenzol - HCB -, dichlordiphenyltrichloroethane - DDT -, dichlorodiphenylethane - DDE -, tetrachlorodiphenylethane - DDD -). Mercury contaminations were seen most commonly and correlated significantly with the number of amalgam fillings and with the release of mercury while chewing. The latter was demonstrated with the so-called chewing-gum test. Women with hormonal disorders or alopecia had, on the average, the highest mercury excretion during the wash-out test. Cadmium excretion was pronounced for the following groups of women: those with technical professions, those suffering from thyroid dysfunctions, and those with habitual abortions and uterine fibroids. With increasing age, pesticide concentrations of the blood rose significantly. Women with endometriosis and with antihyroidal antibodies had significantly higher PCB values. Despite therapeutic intervention, fewer women with elevated DDT/DDE/DDD values conceived when compared to those with lower values. alpha-HCH concentrations were often elevated in women with uterine fibroids. With increasing PCP levels pregnancies often ended in abortion. Results of this investigation indicate that women with hormonal irregularities or specific fertility disorders should be examined for heavy metal and pesticide contamination prior to hormone treatment. PMID- 1285484 TI - [Results of postoperative radiotherapy with iridium-192 in patients with ovarian cancer]. AB - While the surgical and chemotherapeutic therapy is an established procedure for the treatment of ovarian cancer, the role of radiotherapy is not quite clear. We investigated whether the recurrence rate concerning the vaginal cuff and pelvis in ovarian cancer patients can be reduced by postoperative irradiation with afterloading technique. In retrospective analysis 20 patients with ovarian cancer, stage I-IV, received radiological contact therapy with 192-Iridium 2 x 7.5 Gy in 0.5 cm tissue depth after surgical and chemotherapeutic treatment. A control group of 20 patients with similar oncological parameters was formed. In both groups a local recurrence occurred in 6 women, which was confirmed clinically, histologically and by diagnostic devices. After 2 years, 6 of the irradiated patients survived and 11 of the control group. The results show, that the irradiation of the vaginal cuff, as applied in endometrial carcinoma, will not reduce local recurrence rate of ovarian cancer. PMID- 1285485 TI - [Use of xylocaine in placing afterloading applicators in the gynecologic area--a simplified and analgesic method]. AB - The afterloading contact therapy is an established method in the therapy strategies of extended gynecological malignancies. Unfortunately, the manipulations of application are painful in many cases. The results of the present paper suggests, that the pretherapeutic application of Lidocain (Xylocain) may decrease in pain symptomatic significantly. This findings have relevance for ambulant afterloading contact therapy. PMID- 1285486 TI - [Rare site of malignant melanoma]. AB - Primary melanoma of the vagina is a rare tumor associated with a poor prognosis. We report on a 82 years old woman with a malignant melanoma of the vagina. The treatment performed was the removal of the vaginal tumor and a hemivulvectomy followed by a chemotherapy over 6 month. A recurrence of the tumor and the development of metastases in the brain and in the lungs was observed 3 weeks after the end of the chemotherapy. The patient expired 10 month after the primary treatment. PMID- 1285488 TI - [Is lymphography before therapy of invasive cervix cancer a mandatory diagnostic procedure?]. PMID- 1285487 TI - [Systemic lupus erythematosus in puerperium]. AB - Systemic LE is a rare complication in puerperium. A case of an acute exacerbation post partum is reported. The described case brings to attention the fact, that behind febrile conditions in puerperium could stand SLE. PMID- 1285489 TI - [Which CTG changes necessitate fetal microblood examination and which CTG changes necessitate induced labor or cesarean section without microblood examination?]. PMID- 1285490 TI - Granulovacuolar degeneration in the hippocampal cortex of aging and demented patients--a quantitative study. AB - The occurrence and topographic analysis of granulovacuolar degeneration (GVD) in the hippocampal cortex of mentally normal controls (75 cases) and patients with Alzheimer's dementia (AD; 17 cases which included Alzheimer's disease and senile dementia of Alzheimer type), multi-infarct dementia (MID; 16 cases), Pick's disease (PD; 5 cases) and atypical dementia [5 cases; non-Alzheimer, non-Pick dementia with Fahr's syndrome (NANPDF)] were investigated. GVD was rarely found in control cases below the age of 60 years. In elderly normal brains, the statistically most representative ranking order of predilection for GVD (in decreasing severity) was: in the 60 s, CA1 > prosubiculum > CA2 (no GVD was found in the CA3 and CA4); in the 70 s, CA1 > prosubiculum > CA2 > CA3 > CA4; in the 80 s, CA1 > prosubiculum > CA2 > CA3 > CA4; in the 90 s, CA1 > prosubiculum > CA2 > CA3 > CA4. In the brains of demented patients, the rank order for GVD was: for AD, CA1 > CA2 > CA3 > prosubiculum > CA4; for MID, CA1 > prosubiculum > CA2 > CA3 > CA4; for PD, CA1 > CA2 > CA3 > prosubiculum > CA4; and for atypical dementia (NANPDF), CA1 > CA2 > prosubiculum > CA3 > CA4. The similarity of the predilection to ranking order was noted both in normal aged subjects and in MID as well as both in AD and in PD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285491 TI - Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil. AB - It has not been discussed whether transient forebrain ischemia of 5-min duration, which is a model frequently used to evaluate pharmacological protection against ischemic injury, is an optimal model in the CA1 field of this animal whose brain temperature is maintained at normothermic levels. The temperature of the brain during an ischemic insult strongly affects the extent of the resulting neuronal injury. If the brain temperature is not regulated, it usually falls in the gerbil by 2 degrees-4 degrees C during 5-min ischemia. However, the brain temperature during ischemic insult was not regulated in many previous studies. In the present study, the effects of transient (1 to 5 min) forebrain ischemia on the development of neuronal degeneration in hippocampal regions of the gerbil whose brain temperature was maintained at 37 degrees C were examined. In the CA1 field of the hippocampus, transient ischemia of 3- and 4-min duration caused almost the same maximal damage (88%-91% neuronal loss) as observed in the gerbils subjected to 5-min ischemia. Transient ischemia of 2- and 2.5-min duration provoked substantial neuronal damage in 25% and 55% of experimental gerbils, respectively. These results indicate that 5-min bilateral forebrain ischemia is more than is necessary to examine ischemia-induced neuronal degeneration in hippocampal CA1 field of the gerbil whose brain temperature is maintained at normothermic levels. In the normothermic gerbil brain, an ischemic period of 3-min already induces extensive neuronal death in the CA1 and, thus, constitutes a sensitive model to evaluate faint protective effects of drugs against ischemic injury in the normothermic gerbil. PMID- 1285492 TI - Evidence that neurofibrillary tangles undergo glial modification. AB - Ghost tangles, neurofibrillary tangles (NFTs) emerging into extracellular space, appear to be subjected to some microglial association in addition to an invasion of astrocytic processes. Our findings lead us to speculate that the NFTs undergo structural and immunocytochemical modification. Electron microscopic observation of the NFTs in the vascular region indicated either the discharge of NFTs into the vessel or formation of NFTs in the astrocytic end-foot. PMID- 1285493 TI - Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases. AB - Head trauma has been associated with the occurrence of Alzheimer's disease and plays a clear role in the etiopathogenesis of the boxers encephalopathy referred to as dementia pugilistica. Neurofibrillary tangles (NFT), one of the pathological hallmarks of Alzheimer's disease are observed in very high densities in the brains of former professional boxers suffering from dementia pugilistica. In Alzheimer's disease, NFT display striking regional and laminar distribution patterns that have been correlated with the localization of neurons forming specific corticocortical connections. In dementia pugilistica cases, NFT were concentrated in the superficial layers in the neocortex, whereas in Alzheimer's disease they predominated in the deep layers. Thus, the association cortex of brains from dementia pugilistica patients demonstrated an inverse NFT distribution as compared to Alzheimer's disease. This finding suggests that a more circumscribed population of cortical pyramidal neurons might be affected in dementia pugilistica than in Alzheimer's disease. PMID- 1285494 TI - Developmental alteration of serotonin neurons in the raphe nucleus of rats with methylazoxymethanol-induced microcephaly. AB - Prenatal exposure of pregnant rats to methylazoxymethanol acetate (MAM), an anti mitotic agent, on day 15 of gestation induces severe microcephaly in the offspring. The present study first investigated a developmental alteration of serotonin (5HT) neurons immunohistochemically in the dorsal and median raphe nuclei in serial sections in both control and microcephalic rats (MAM-rats) at 35 days of age. 5HT-immunoreactive neurons in the MAM-rats were reduced in number and irregularly distributed in the dorsal and median raphe nuclei compared with those in the control. The dendrites of neurons in these nuclei in the MAM-rats were very short and twisted. A follow-up observation on the development of the cerebral cortex at 5, 9 and 28 days of age was performed using Nissl-stained preparations, which revealed a disorganized cell arrangement in the cerebral cortex of the MAM-rats at the very early postnatal period. Furthermore, the distribution of 5HT-immunoreactive fibers into the cerebral cortex was also examined using brains of 28 days of age. In MAM-rats of this age, abnormally tortuous 5HT-immunoreactive fibers were observed in the cerebral cortex. 5HT neurons in the raphe nuclei are known to project their ascending axons widely into the entire cortical area during the 1st postnatal week. Thus, the association of disorganized cortical cell arrangement and the hyperdense and tortuous distribution of 5HT-immunoreactive fibers in the cerebral cortex support the idea of target-dependent secondary degeneration of 5HT neurons in the dorsal and median raphe nuclei of the MAM-rats. PMID- 1285496 TI - Mapping of neurofibrillary degeneration in Alzheimer's disease: evaluation of heterogeneity using the quantification of abnormal tau proteins. AB - A biochemical mapping of neurofibrillary degeneration was performed in Brodmann areas of the brains of five patients with senile dementia of the Alzheimer type (AD). To quantify the degenerating process, we used an immunoblot method with antibodies directed against the abnormally phosphorylated tau proteins named Tau 55, 64 and 69, known to be early and reliable markers of the degenerating process in AD. The detection intensities were assessed using a numerical rating scale for each area and scores were grouped by lobe. In all cases, the detection of Tau 55, 64 and 69 was positive in all areas except in primary visual cortex (area 17) for two patients. The detections were especially strong in temporal neocortical and limbic areas and were higher in associative cortex than in primary sensory cortex. Scores from the occipital and frontal lobes differed strongly between patients as compared to the uniform degree of detection in the limbic, temporal and parietal lobes. Despite a relatively identical duration of the disease and an apparently global involvement of the cerebral cortex, the distribution of neurofibrillary degeneration in AD varies significantly across cortical areas and displays striking heterogeneity patterns along the rostrocaudal axis. The immunodetection of abnormal tau proteins using the Western blot method may provide complete and rapid quantitative data of the degenerating process in AD. PMID- 1285495 TI - Nuclear and mitochondrial changes of muscle fibers in AIDS after treatment with high doses of zidovudine. AB - Zidovudine (formerly azidothymidine) is a potent inhibitor of the human immunodeficiency virus (HIV) reverse transcriptase and represents the first approved drug showing clinical efficacy in HIV-associated diseases. However, considerable toxicity causing macrocytic anemia, neutropenia, and myopathy has been reported, with severe mitochondrial alterations as a special feature of this myopathy. The mitochondrial changes are consistent with the fact that zidovudine acts as an inhibitor of the mitochondrial gamma-polymerase. Electron microscopically, we could confirm the presence of severely altered mitochondria in a 32-year-old male, who developed a necrotizing myopathy after daily administration of 1,000 mg zidovudine over a period of 15 months. In addition, there were even more severe nuclear changes that, for the most part, have not been documented electron microscopically in HIV-related myopathy either with or without zidovudine treatment, especially in non-necrotic and non-regenerating fibers. Since various in vitro studies have shown interference of zidovudine with nuclear DNA metabolism even in human cell lines, we assume that the nuclear changes that we observed are at least in part related to zidovudine treatment. PMID- 1285497 TI - Ibotenic acid-induced calcium deposits in rat substantia nigra. Ultrastructure of their time-dependent formation. AB - The excitotoxin ibotenic acid (IBO) induces local calcium deposits upon injection into rat substantia nigra. Their formation has been investigated at the ultrastructural level in a time course study from 2 days to 8 weeks survival. Potassium bichromate stain was used to visualize pathological calcium accumulation. Two days after IBO application, reaction product for calcium was observed in mitochondria of degenerating perikarya and dendrites, but not in axons, boutons or glia. Four days after the lesion, calcium stain was found, in addition, in a seemingly free form in a few dendrites, especially those still contacted by intact boutons and not sequestrated by invading glia. Two days later, most of these calcium-accumulating dendrites were separated by astroglia from their synaptic partners. At the border between glia and dendrite a fibrillar matrix was formed which further accumulated calcium. During the following weeks this matrix enlarged stepwise and was infiltrated with calcium, thus giving a picture resembling the annual growth rings of trees. The evolving bodies incorporated smaller deposits in their vicinity, finally representing the large concretions seen at the light microscopic level from the 4th postoperative week onward. Similarities and dissimilarities of these observations with the results from other ultrastructural studies on excitotoxin lesions are detailed. It is suggested that the different outfit of neuronal subpopulations and of glia with ligand-gated and metabotropic glutamate receptors in the single brain region, as well as the local response repertoire of glial cells towards the excitotoxic injury with the subsequent formation of a calcium-accumulating matrix provide the molecular basis for the formation of calcium deposits. PMID- 1285498 TI - Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. AB - The understanding of delayed hippocampal death as a therapeutic window for post ischemic treatment of the brain has led to numerous investigations focusing upon underlying cellular mechanisms and pharmacological potentials in gerbils and rats. Nevertheless, studies on the occurrence of delayed neuronal death in the human brain have been singular and dealt with only small files of patients. To complement these limited data, in the present study 26 adult patients with a history of a single cardiac arrest were included. Following successful resuscitation, individual survival ranged from less than 1 h to 186 days (mean = 11 days). The severity of the resultant ischemic injury in hippocampus CA1, among Purkinje cells, or in frontal neocortex, respectively, was quantified by direct counting of necrotic neurons. Additionally, hippocampal specimens were immunostained for neuron-specific enolase. The data obtained demonstrate the occurrence of delayed neuronal death in human hippocampus and, in a minor form, in cerebellar Purkinje cells. This is in contrasts to the immediate manifestation of ischemic neuronal necrosis in the neocortex. Unlike previous findings in experimental animals and in humans, the delay of CA1 cell death could be defined as lasting about 7 days following cardiac arrest. Moreover, the immunohistochemical results indicate delayed neuronal recovery in CA1, which in the time course reciprocally corresponds to delayed manifestation of hippocampal neuronal death. Interpretation of the results must consider the lack of information about the exact individual duration of cardiac arrest and resuscitation, as well as missing data concerning pre-ischemic physiological variables. PMID- 1285499 TI - Desmin and vimentin as markers of regeneration in muscle diseases. AB - Localization and distribution of desmin and vimentin have been studied in different neuromuscular disorders using monoclonal antibodies. We have demonstrated that vimentin, although virtually absent in normal human muscle fibers, is expressed in regenerating fibers in different neuromuscular disorders. Moreover, these fibers showed a strong positivity with desmin antibodies. In normal muscle fibers desmin is only localized at Z-line level. These results suggest that desmin and vimentin may be over-expressed during muscle regeneration processes, probably because of their importance in the structural organization of the sarcomere. PMID- 1285500 TI - Histopathological effects of intracerebral injections of human recombinant tumor necrosis factor-alpha in the rat. AB - Human recombinant tumor necrosis factor-alpha (rTNF-alpha) was administered to normal Fischer 344 rats by stereotaxic intracerebral (IC) injection. Animals received a single injection of either 6 x 10(4) U rTNF-alpha or excipient in their right parietal lobe. Others received three consecutive daily injections of either 6 x 10(4) U rTNF-alpha or excipient to examine effects of higher accumulative doses. Histological examination of the brain revealed that both single and multiple IC injections of rTNF-alpha triggered an immigration of circulating leukocytes into the site of TNF-alpha injection. After one injection, this cell population was composed mainly of macrophages and neutrophils. Maximal leukocytic influx occurred by 48 h and was composed mostly of neutrophils which were limited to the injection site and perivascular space. Quantitation of the inflammatory reaction by measurement of tissue myeloperoxidase levels supported these histological observations. One day after multiple rTNF-alpha injections, leukocytic adhesion to endothelium, vascular cuffing and leukocytic infiltration into the neuropil was observed at levels comparable to those seen 3 days following a single rTNF-alpha injection. We conclude that while one or more IC injection(s) of 6 x 10(4) U rTNF-alpha was well tolerated in normal rats, at this dose the cytokine triggers a pronounced leukocytic infiltration at the site of injection. These results support a role for TNF-alpha as a mediator in inflammatory responses within the central nervous system. PMID- 1285501 TI - The inhibition of lymphocyte blastogenesis by asparaginase: critical role of glutamine in both T and B lymphocyte transformation. AB - L-Asparaginase has long been used in the treatment of acute lymphoblastic leukemia or malignant lymphoma in childhood. To determine cell type specific sensitivity to this drug, the L-asparaginase-mediated inhibition of blastogenesis of human peripheral T or B lymphocytes was compared. The rate of incorporation of [3H]-thymidine into the DNA of either T lymphocytes due to phytohemagglutinin (PHA) or B lymphocytes due to Staphylococcus aureus Cowan I (SAC) was measured by the addition of Escherichia coli L-asparaginase in the medium. The blastogenic response of either T or B lymphocytes was also determined in medium depleted of exogenous asparagine and/or glutamine, both of which are hydrolyzed by this enzyme. The in vitro blastogenesis of either human T lymphocytes due to PHA or B lymphocytes due to SAC was inhibited by the inclusion of asparaginase in the medium. The deprivation of exogenous asparagine did not have any inhibitory effect on the blastogenic response of both T and B lymphocytes to each mitogen. On the other hand, the glutamine concentration in the culture medium provided a critical influence on the proliferative response of T and B lymphocytes. The rate of incorporation of [3H]-thymidine into DNA was increased markedly as the concentration of glutamine was increased from 2(-7)-2 mmol/l. It is concluded that the mechanism of inhibition of PHA- or SAC-stimulated lymphocyte blastogenesis by L-asparaginase is not asparagine deprivation but glutamine deprivation. Glutamine, which is the most abundant amino acid, is thought to have an important role in the immune response of lymphocytes. PMID- 1285502 TI - Treatment of Kawasaki disease using the intravenous aspirin anti-inflammatory effect of salicylate. AB - Serum salicylate concentrations were measured in 60 patients with acute phase Kawasaki disease (KD), who were treated with intravenous aspirin (IVASP), to evaluate its anti-inflammatory effect in the treatment of KD. Patients with serum salicylate concentrations > or = 150 micrograms/ml showed shorter durations of fever (7.1 +/- 2.0 vs 10.4 +/- 6.6 days; P < 0.05), shorter durations of positive serum C-reactive protein (14.6 +/- 4.5 vs 22.3 +/- 10.6 days; P < 0.01) and lower incidences of coronary arterial involvements (0/10 vs 6/24; P < 0.05) than did patients with serum salicylate concentrations < 150 micrograms/ml. Significant linear correlations were recognized between daily IVASP dosage and serum salicylate concentrations (r = 0.73; P < 0.01), and between serum salicylate concentrations and serum free salicylate concentrations (r = 0.82; P < 0.01). These correlations did not differ between the presence and absence of coronary arterial involvements. Based on these findings we concluded that a beneficial anti-inflammatory effect in the treatment of KD is achieved when the serum salicylate concentration is > or = 150 micrograms/ml, and that such concentrations could be achieved by increasing the daily IVASP dosage to 100 mg/kg per day or more. PMID- 1285503 TI - Disodium cromoglycate in the treatment of bronchopulmonary dysplasia. AB - Bronchopulmonary dysplasia (BPD) has become the most common form of chronic lung disease in the neonate. Recently, we have experienced a severe case of BPD and examined the effect of disodium cromoglycate (DSCG) on BPD. The gestational age and birthweight of the patient were 27 weeks and 1,000 g, respectively. Although RDS subsided after surfactant replacement therapy, the arterial-alveolar oxygen tension ratio (a/APO2) gradually decreased and FiO2 increased with age, respectively, and pure oxygen supplementation was eventually required after 67 days of life. The DSCG treatment was commenced at 80 days of life. After 6 days of the inhalation therapy, a/APO2 gradually increased. After 10 days of the treatment, the baby was extubated. While the baby was intubated, intratracheal lavage fluid samples were obtained. Eosinophilic cationic protein (ECP) and polymorphonuclear (PMN) elastase concentrations were determined. ECP and PMN elastase concentrations of intratracheal lavage fluids gradually decreased with the DSCG treatment. These results may indicate that DSCG has led to an improvement of pulmonary function and facilitated weaning from mechanical ventilation in an infant with BPD. PMID- 1285504 TI - The 11q- syndrome with mosaic partial deletion of 11q. AB - A female child with mosaic partial deletion of 11q is reported. At 1 month of age she was presented with cogenital glaucoma, trigonocephaly and multiple minor anomalies. She exhibited growth retardation and the typical phenotype of 11q- syndrome. G-banding analysis failed to show any abnormality, although subsequent high resolution banding revealed the abnormal karyotype 46,XX,del(11)(q23.3 q24.2)/46,XX,del(11)(q23.3 q25). This case is a second case of mosaic 11q- syndrome and her karyotype suggests that the region of 11q23.3-11q24.2 is critical in 11q-syndrome. Congenital glaucoma has never been reported as a complication of 11q- syndrome. PMID- 1285505 TI - Successful collection of peripheral blood stem cells from an infant with acute lymphoblastic leukemia using the Haemonetics V50. AB - Peripheral blood stem cells (PBSC) were collected using the Haemonetics V50 from an 8 month old infant weighing 7.8 kg suffering from acute lymphoblastic leukemia in the first complete remission. Leukapheresis was performed according to an exchange transfusion procedure by the two arm method using only a single lumen Broviac catheter. No problem occurred in the patient during this procedure except for a reduction (by half) of the initial platelet count. This method enables one to collect PBSC very safely, even from infants, in a manner that is painless for patients. PMID- 1285506 TI - Two children with bromate intoxication due to ingestion of the second preparation for permanent hair waving. AB - We report two children who suffered from sodium bromate intoxication due to ingestion of the second preparation for permanent hair waving (the second permanent preparation). One child suffered from gastrointestinal symptoms only. The other exhibited slight acute renal insufficiency. Results of the histological examination of the kidney in the sick child with acute renal insufficiency showed sporadic epithelial separation of the proximal tubuli under light microscopy. In addition, we could demonstrate more clearly epithelial separation and unbroken tubular basement membranes under electron microscopy (EM). To our knowledge, this is the first report of EM findings in this disease. The mechanism of epithelial injuries by bromate is not clear. PMID- 1285507 TI - Neonatal adrenal hemorrhage detected antenatally. AB - This report describes two cases of neonatal adrenal mass detected antenatally by routine ultrasound (US) examination of pregnant women. Case 1 was recognized by the fetal US at 31 weeks gestation. The mass, located near the right upper pole of the kidney, was echolucent on US examination. A serial US of the mass showed changes of the internal echoes from a cystic lesion to a mixed lesion, and finally to a hyperechogenic lesion due to a neonatal adrenal hemorrhage (NAH). At 33 days, laparotomy was performed, and the pathological finding revealed an NAH owing to the mass bleeding into the adrenal cyst. Case 2 was also detected by fetal US just before birth. The mass of the right upper pole of the kidney was hyperechogenic on US examination. The baby clinically deteriorated after birth because of hypovolemia owing to NAH. A serial US of the mass showed the change from a hyperechogenic to a cystic lesion. Four months later, the mass spontaneously resolved. From the US spectrum, the mass was diagnosed as NAH. These are the second known cases of NAH detected before birth in Japan. PMID- 1285508 TI - Survival rate of extremely low birthweight infants and its effect on the amendment of the Eugenic Protection Act in Japan. AB - Because of the increasing survival rate of extremely low birthweight infants in recent years, the viability limit in the Eugenic Protection Act in Japan was amended from 24 to 22 completed weeks of gestation. The Japan Pediatric Society's survey on the outcome of infants born in 1990 focused on infants born before 24 weeks gestation and less than 500 g. The survival rates of infants born in 23, 22 and before 22 weeks gestation overall at 511 hospitals throughout Japan were 43/118 (36%), 3/36 (8%) and 0/8 (0%), respectively. Of 16 infants, none weighing less than 400 g at birth survived but 16 (12%) of 50 infants between 400 and 499 g survived. Up-to-date statistical data is essential to the amendment of the concept of viability and subsequent ethical decision-making on extremely low birthweight infants. PMID- 1285509 TI - Surfactant replacement therapy in premature babies with respiratory distress syndrome: factors affecting the response to surfactant and comparison of outcome from 1982-86 and 1987-91. AB - The impact of surfactant therapy on chronic lung disease remains uncertain. During the past decade (1982-91), over 300 babies with respiratory distress syndrome (RDS) weighing 501-2,500 g at birth were consecutively treated with surfactant-TA at our neonatal intensive care unit. Data on 95 RDS babies treated in the first 5 year period (Period 1, 1982-86) were compared with those on 158 RDS babies treated in the second 5 year period (Period 2, 1987-91). Overall respiratory improvement was better in Period 2 than in Period 1. In Period 2, surfactant therapy converted 98% of the babies with moderate/severe RDS to those with 'near normal' lung by 72 hr post-treatment. In Period 2, 95% of the surfactant-treated babies weighing 501-1,750 g at birth survived, 97% of which required no supplemental oxygen at 40 weeks corrected gestational age. Increased survival rate in the surfactant-treated babies during the past decade has not been followed by a parallel increase in chronic lung disease. The severity of the initial pulmonary disease per se was not the significant risk factor for chronic lung disease. Several other variables affecting the response to surfactant therapy and outcome have been identified by stepwise logistic regression analysis and include factors related to perinatal events such as birth asphyxia and infection, and other complications of prematurity. PMID- 1285510 TI - High frequency oscillation. AB - The current state of high frequency oscillation (HFO) in Japan is reviewed. The discussion is focused on the following: (i) the repeated application of short duration SI (sustained inflation) is effective in recruiting lung volume and increasing PaO2; (ii) HFO can prevent the formation of granulocytes related to lung injury; and (iii) HFO does not increase the risk of severe complications such as air leaks, bronchopulmonary dysplasia or intraventricular hemorrhage. PMID- 1285511 TI - Pulmonary surfactant apoprotein-A in neonates with different respiratory disorders. AB - A serial determination of pulmonary surfactant apoprotein-A (SP-A) was made on tracheal aspirates from seven intubated infants with different types of respiratory failure in the first week of life. A two-site immunoassay with monoclonal antibodies was adopted to determine the SP-A concentration. The concentrations of albumin in the same samples were also assayed, and these data were expressed as the ratio of SP-A to albumin (SP-A/albumin ratio), and evaluated against clinical data such as the arterial-alveolar oxygen tension ratio (a/APO2) or ventilatory index. In infants with respiratory distress syndrome, the SP-A/albumin ratio was initially low, and increased gradually in the first few days of life with the improvement of a/APO2 and ventilatory index. The complication of pulmonary hemorrhage due to patent ductus arteriosus (PDA) resulted in a temporary decrease in the ratio. The infant with transient tachypnea of the newborn showed higher concentration from the first day of life and, in the course of PDA without pulmonary hemorrhage, the ratio did not decrease. The cases of congenital pneumonia showed the SP-A/albumin ratio remaining low while the infection was evident. These data suggest that the SP A/albumin ratio of the tracheal aspirate can be used for the quantitative and qualitative evaluation of endogenous pulmonary surfactant in newborn infants with different respiratory disorders. PMID- 1285512 TI - Determination of serum unbound bilirubin for prediction of kernicterus in low birthweight infants. AB - Serum unbound bilirubin concentrations (UBC) and serum total bilirubin concentrations (TBC) were measured serially in 138 low birthweight (LBW) infants treated with phototherapy for non-hemolytic hyperbilirubinemia. We attempted to assign the suitable critical UBC levels for predicting bilirubin encephalopathy into two different birthweight groups: a very low birthweight (VLBW) group (birthweight < 1,500 g) and an LBW group (birthweight between 1,500 g and 2,499 g). Twelve infants were diagnosed as 'at risk' for kernicterus, of whom 11 had signs of acute bilirubin encephalopathy and received exchange transfusion. One VLBW infant had neurological sequelae at a 3 year follow-up, although exchange transfusion was not carried out because of low TBC. Sensitivity and specificity for predicting kernicterus were calculated at different UBC levels between 0.6 microgram/dl and 1.5 micrograms/dl and TBC levels between 8 mg/dl and 26 mg/dl. The receiver-operating characteristic (ROC) curves plotted for UBC as a predictor of kernicterus were clearly shifted up and to the left compared with the curves for TBC in the VLBW and LBW groups. Thus, the UBC measurement may well provide a more rational basis for evaluating the risk of kernicterus in LBW infants. The optimal cut-off points were derived from these curves. In the VLBW group, the sensitivity was 100% and the specificity was 96% for a UBC of 0.8 microgram/dl, and 80% and 64% for a TBC of 11 mg/dl. In the LBW group, the sensitivity was 100% and the specificity was 98% for a UBC of 1.0 microgram/dl and 71% and 78% for a TBC of 16 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285513 TI - Postnatal growth curves of very low birthweight Japanese infants. AB - To construct standard growth curves for Japanese infants of very low birthweight, longitudinal data provided by 47 neonatal centers in Japan were reviewed. Data were collected on the growth of infants admitted to those units during 1986 and 1987 and who survived beyond 3 years of age. A total of 379 singleton infants, who were free of neurological sequelae and appropriate for gestational age, were enrolled. Those whose birthweights were more than 600 g and less than 1,500 g were grouped into nine weight categories separated by increments of 100 g. Data on the increase in weight and head circumference were compiled and analyzed until more than half the infants in each weight category had been discharged from each site. Growth curves of bodyweight and head circumference in the nine groups were constructed using polynomial regression analysis to define the curve of best fit. With increasing prematurity, significant trends of greater weight loss (P < 0.05), longer time to reach the lowest weight (P < 0.01) and a longer time to regain birthweight (P < 0.01) were observed. In addition, there was a significantly higher incidence of chronic lung disease in such groups (P < 0.0001). Growth curves were characterized by the average clinical profiles in each of the nine groups. We believe that these data will be useful in evaluating the growth of very low birthweight infants being cared for in modern neonatal intensive care units in Japan. PMID- 1285514 TI - Prevention of perinatal transmission of hepatitis B virus carrier state. AB - By means of passive and active immunization with hepatitis B immunoglobulin and hepatitis B vaccine, 396 of 407 babies born to hepatitis B antigen-positive carrier mothers, were protected from establishing the hepatitis B virus (HBV) carrier state during a follow-up period of 12 months or longer. Four infants developed the HBV carrier state before the completion of the immunoprophylaxis schedule, and another seven developed the state after the completion of the schedule. Seroconversion of anti-HBc was observed in 26.8% of the successfully protected infants. In Japan a nationwide program to prevent the vertical transmission of HBV with these procedures was established in 1986, and so liver diseases due to HBV are expected to be eliminated in the near future. PMID- 1285515 TI - Oxygen and reduced umbilical blood flow trigger the first breath of human neonates. AB - The mechanism triggering the first breath of human neonates is still unclear. In order to investigate the role of oxygen and umbilical blood flow in the onset of the first breath, a total of 20 rat and rabbit fetuses were studied. All five rat fetuses delivered in a nitrogen chamber did not commence breathing of their own accord, whereas all five rabbit fetuses delivered in oxygenated fluorocarbon fluid commenced their own breathing, suggesting that contact with oxygen rather than release from submergence is more crucial in the initiation of the first breath. PMID- 1285516 TI - Epidemiology of neonatal chronic lung disease in Japan. AB - A nationwide survey on the epidemiology of chronic lung disease (CLD) of the newborn was conducted. Questionnaires were sent to 391 level II and III neonatal centers in Japan and the registration of infants born in 1990 with chronic lung disease was requested. CLD was defined as an oxygen requirement greater than that obtainable in room air at 28 days after birth, with symptoms of persistent respiratory distress and a hazy or emphysematous and fibrous appearance on chest X-ray. A total of 301 neonatal centers (77.0%) responded and 50,290 infants at these centers were registered. Of these, 97% survived the first month and 1,135 of 48,762 neonatal survivors developed CLD. The mortality of infants with CLD was 6.2%. Survival rates at 28 days of age increased consistently with birthweight. Survival at 28 days of age in infants below 1,000 g at birth was 73.7%, but the rate was 93.9% in infants weighing 1,000-1,499 g. The incidence of CLD was inversely proportional to birthweight. Approximately one quarter of neonatal survivors with a birthweight below 1,500 g and approximately half of extremely small infants ( < 1,000 g) developed CLD. The analysis of CLD infants showed that 28.2% of them had a history of respiratory distress syndrome (RDS) and a typical fibrous appearance on chest X-ray (Type I), while 29.3% also had a history of RDS but had an atypical X-ray appearance (Type II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285517 TI - Effect of mean airway pressure on bronchial mucosal blood flow in rabbits with oleic acid-induced injury. AB - The effects of mean airway pressure (MAP) on bronchial mucosal blood flow at the carina in nine anesthetized adult rabbits undergoing high frequency ventilation were studied. The animals were given oleic acid to diminish lung compliance and to exclude the influences of increasing MAP on systemic venous return. Mucosal blood flow decreased significantly when MAP exceeded 14 cmH2O. Mucosal blood velocity tended to decrease as higher levels of MAP were applied. Mucosal blood volume decreased significantly when MAP exceeded 20 cmH2O. Hemodynamics, arterial blood gas values and pH were not changed significantly. Our data demonstrate that bronchial mucosal blood flow decreases at high levels of MAP even if cardiac output remains constant. Hence this decrease of bronchial mucosal blood flow may be due to the transmission of pressure to submucosal bronchial capillaries. PMID- 1285518 TI - [13C] breath test of medium-chain triglycerides and oligosaccharides in neonates. AB - It is suitable to examine the utilization of carbohydrates and fats using stable isotope-labelled substrates in neonates because of their non-radioactivity. Administering medium-chain triglycerides (MCT) and oligosaccharides is of use in enteral nutrition for a patient with a limited water intake such as a neonate. In this study, the oxidation of MCT and maltose administered orally as an energy supplement in neonates has been examined using a stable isotope-labelled breath test. Five normal term neonates and five growing preterm infants were given [13C] trioctanoin orally and three growing preterm infants were given [13C]-glucose and [13C]-maltose orally. The [13C] enrichment in carbon dioxide was analyzed by isotope ratio mass spectrometry, and oxidation rates over 6 hr and 12 hr respectively, were calculated. The oxidation rates for [13C]-octanoin after 6 hr were 46.2 +/- 3.6% in preterm infants and 53.5 +/- 13.8% in normal neonates, respectively (no significant difference), and 58.4 +/- 9.4% and 52.8 +/- 6.0% for [13C]-glucose and [13C]-maltose, respectively (not significant). The results demonstrate that orally administered MCT and maltose are oxidized sufficiently in preterm infants. PMID- 1285519 TI - [Renal angiomyolipoma: study of 39 patients and general review]. AB - Between 1969 and 1991, 39 patients totalling 48 renal units with renal angiomyolipoma (RAMP) were diagnosed and treated in the Urology Service of the Hospital La Paz. In 5 patients, RAMP was part of a tuberous sclerosis, and was isolated in the remaining ones. RAMP was symptomatic in 32 cases (32/48 = 66.6%), 10 with Wundrelich's syndrome, and in 24 cases (24/48 = 50%) was larger than 4 cm. In the first cases of our series, clinical diagnosis through renal arteriography was achieved in 33% (5/14) cases; later, with the arrival of ultrasound and CAT, pre-operative diagnosis was possible in 88% (30/40) of cases. There was also 2 periods with regard to treatment, the initial one with predominance of radical surgery and the present one of observation and/or conservative surgery depending on size as well as signs and symptoms. Overall, 23 nephrectomies, 2 partial nephrectomies and 6 tumorectomies were performed, while there has been 17 cases (with no histological confirmation) treated with conservative approach and followed-up with ultrasound and CAT. With an average follow up of 8.4 years (range: 0.5-20 years), there has been no local or metastatic relapse of RAMP. There was one case of lymphatic affection which was explained as evidence of RAMP's multifocal condition and not as an indication of malignancy. In 3 patients, histological examination revealed coexistence of RAMP and renal carcinoma; 2 of these patients who underwent nephrectomy are free of disease; the third patient, treated with conservative surgery (tumorectomy), showed renal carcinoma relapsed after 2 years and had it removed. RAMP's incidence, histogenesis, diagnostic methods and treatment criteria are discussed. PMID- 1285520 TI - [Urologic complications in renal transplantation: our experience with 200 cases]. AB - Urinary tract complications continue to be a major cause of morbidity in renal transplant patients. This paper is a review of the urological complications developed in in 200 renal transplants performed in our service over a 10-year period, from January 1980 to December 1989, with a follow-up of at least 1 year. We include a total of 29.5% urological complications, subdivided in two sections each corresponding to a distinct period during which different procedures were used in the renal transplantation unit. The report includes an analysis of the complications' etiopathogenic, diagnostic and therapeutic factors. PMID- 1285521 TI - [Epidemiology of urologic pediatric emergencies in our hospital, 1990]. AB - The article's objective is to study the epidemiological patterns which define the paediatric urological emergencies within the area of influence of our hospital. To this end, 187 protocols of the paediatric emergencies attended by the urologist in 1990 were retrospectively reviewed. The most frequently observed pathologies were balanitis-phimosis, acute scrotum and genito-urinary injuries. A clear relationship of the type of disease to the patient's age and treatment, as well as some time-related variations were observed. About 40% of all cases could had been treated at a non-emergency outpatient clinic. PMID- 1285522 TI - [Cystolysis. Supratrigonal denervation]. AB - CI is an entity with obscure etiopathogenesis and difficult to manage. This essay contributes three cases, out of a series of 25, were cytolisis was performed. Results after six months follow-up are very encouraging, since pain has disappeared in all cases and pollakiuria has been radically reduced. PMID- 1285523 TI - [Endourologic treatment of tumor of the upper urothelium: results and clinical course]. AB - Presentation of 31 patients with suspected diagnosis of upper urothelium tumour seen between 1986 and 1991. In agreement with our study protocol and the endourological treatment followed in this type of tumours, there were eight false positive, which were excluded. Five cases were treated by retrograde ureterorenoscopy while in the remaining 18 cases the anterograde percutaneous approach was used. A review of both the aspects of endourological treatment and the evolution of these patients during that period is included. PMID- 1285524 TI - [Supernumerary kidney with ectopic ureteral opening to the vagina associated with horseshoe kidney]. AB - Contribution of one case of supernumerary kidney with ureter ectopically opened to vagina associated to horseshoe kidney. Supernumerary kidneys are extremely unusual entities, there being only about 70 cases described in the international literature. This is the first case where it is found associated to horseshoe kidney. PMID- 1285525 TI - [Seminal vesicle cyst and ipsilateral renal agenesis: frequent association]. AB - Presentation of a new case of cyst of the seminal vesicle in one patient with ipsilateral renal agenesis, stressing the frequency of this association. The cyst become evident following confirmation of renal agenesis, and presented an unusual communication to the bladder due to previous surgery (transurethral resection). This diagnosis was only suspected in the computerized tomography and cystoscopy and later confirmed by deferentovesiculography. The relevance of exploring any possible dysplasia of the seminal tract in the presence of renal agenesis is stressed. From an embryological point of view, the close relationship during development of both urinary and reproductive systems appear to explain the coexistence of these two anomalies. The primary symptoms of the condition, including the unspecific ones, as in the present cases, are discussed. Differential diagnosis from other deep pelvic cysts is referred. Following a literature review and based in our personal experience, already published, our views on the different embryological, clinical, diagnostic and therapeutic considerations are established. PMID- 1285526 TI - [Bladder endometriosis]. AB - Endometriosis is the ectopic location of the endometrium. It is quite unusual to find endometrium foci within the vesical cavity, this experience representing only 1-2% of all possible locations. This paper contributes one vesical endometriosis in a 35 year old woman endoscopically diagnosed because of a solid tumour with surface bluish bullae or cysts. We used Gestrima, in dosage of 2.5 mg twice weekly, as adjuvant treatment to endoscopic surgery with complete objective response. PMID- 1285527 TI - [Paravesical tumor of adrenal gland residues]. AB - Presentation of one case of ectopic suprarenal tissue residues' tumour found at paravesical level. The singularity of this diagnosis, unless hormonally active, or when very large in size, as well as its various locations is recalled. Ultrasound, CAT and hormone characterization are the mainstays to achieve clinical diagnosis. Surgery is always the course adopted. Only when such an option is unsuitable, drugs are used to block the steroidogenesis. PMID- 1285528 TI - [Subcapsular hematoma after ESWL]. AB - Contribution of 2 cases of post-ESWL subcapsular haematoma in patients with HBP. One of them underwent surgical drainage. In the second case a more conservative attitude was followed. Review of related literature. PMID- 1285529 TI - [Prostatic syndrome as presentation form of non-Hodgkin's lymphoma]. AB - Description of one case of a 66 years old patient who developed prostatic syndrome with obstructive renal insufficiency. The ultrasound study showed the existence of a large prostatic mass diagnosed by means of a biopsy as a non Hodgkin lymphoma. The thoraco-abdominal computerized tomography ruled out the presence of distant adenopathy while bone marrow biopsy did not show lymphoma infiltration. Subsequently, the patient was given polichemotherapy following a CHOP scheme. After 6 cycles, a second CT was performed that showed disappearance of the previously described prostatic mass. Chlorambucil was given as maintenance therapy. The patient remains asymptomatic and disease-free nine months after discontinuing the polichemotherapy. PMID- 1285530 TI - [Renal angiomyolipoma in childhood: a clinical case]. AB - The renal angiomyolipomas are unusual benign tumors which more than 50 per cent, are associated with tuberous sclerosis or intestinal linphangiomatosis. They can be discovered in a radiologic study by chance or to be associated with flank and abdominal pain and hematuria. The ultrasonographic imagen is characteristic and its management is conservative. PMID- 1285531 TI - [Post-natal development of interstitial Leydig cells in rat testicle]. AB - The existence of different stages of postnatal activities in Leydig's cells, as demonstrated in hormone studies, appears to be fully admitted. Such occurrence should have repercussions on the population of those elements primarily entrusted with their production, either in the number of elements or their activities. The present article studies Leydig's cells rate in Wistar rats over the postnatal stage, from birth to adulthood. During this postnatal stage, Leydig's cells population does not actually disappear. There is a decrease immediately after birth and up to the age of 21 days when gonadal drop occurs in this species, and from there on a considerable increase takes place for in a two-month period they multiply by ten. On the other hand, it is highly surprising the great speed of testicle growth up to the age of 60 days, reaching maximum size at 90 days. The increase is due to the growth of the tubular compartment. PMID- 1285533 TI - Evaluation of the use of transported chilled stallion semen in Sweden, 1987-1991. PMID- 1285532 TI - Equine artificial insemination in Central and East Europe. PMID- 1285534 TI - Use of frozen stallion semen in Europe. PMID- 1285535 TI - Cryopreservation of stallion spermatozoa. PMID- 1285537 TI - Influence of conservation method on the motility and morphology of stallion semen (an international project). PMID- 1285536 TI - Automated analysis of stallion semen post-thaw motility. PMID- 1285539 TI - Sperm morphology in stallions in relation to fertility. PMID- 1285538 TI - Evaluation of the stallion for breeding. PMID- 1285540 TI - Evaluation of cryopreserved semen: an alternative assay. PMID- 1285541 TI - Current practical use of a glasswool/Sephadex filtration technique of frozen stallion semen. PMID- 1285542 TI - Infectious agents in equine semen. PMID- 1285543 TI - Techniques for collection and storage of stallion semen with minimal secondary contamination. PMID- 1285544 TI - Sperm production in the stallion. PMID- 1285545 TI - Ultrasonography: a new diagnostic tool in stallions with genital tract infection? PMID- 1285546 TI - Interactions between sperm packaging, gas environment, temperature and diluent on fresh stallion sperm survival. PMID- 1285547 TI - Drugs for impotence. PMID- 1285548 TI - AZT is a dangerous abbreviation. PMID- 1285549 TI - Update on otitis media. Part 1. Epidemiology and pathophysiology. PMID- 1285550 TI - Understanding mail order pharmacy users. PMID- 1285551 TI - Users' perceptions of mail-service pharmacy. AB - This survey studied the satisfaction of university employees with the mail service pharmacy option of their major health insurance provider. Nearly 92% reported good or excellent satisfaction with the mail order service. Of the 76.5% who reported receiving drug information brochures with some or all of their prescriptions, 91.5% rated the information excellent or good. When asked what sources they used to get additional information, 31.2% used a mail service pharmacist. These data suggest that mail order pharmacies, which have increased volume 50% per year since 1981, can expect to maintain and expand their market share. All pharmacy sectors should use this information to determine ways to enhance their competitive position. PMID- 1285552 TI - One pharmacist's work for AIDS patients. PMID- 1285553 TI - The realities of managed health care and pharmacy practice. PMID- 1285554 TI - Prospects for controlled-delivery systems. AB - Americans seem to view medical progress as a citizen's entitlement. They expect, and researchers expect to seek, cures for acquired immunodeficiency syndrome (AIDS), Alzheimer's disease, cancer, and other deadly or incapacitating diseases. Both the public and researchers also seem undaunted by the cost. CDS technologies and biotechnology drugs are making this expectation possible. Still, CDSs may not dispel public resentment over the high cost--and profit--of discovering otherwise welcomed new healing molecules. As noted by 1988 Nobel laureate in medicine, Sir James Black: "I think both the press and industry have failed to communicate to the public that behind every little pill is a vast amount of high technology...." With increasing use of and satisfaction from CDSs, more of these mechanisms, covering a broadening spectrum of uses, will be marketed. Because these products are taken less often, patient compliance is expected to increase. As more CDSs are introduced, dispensing frequency will decline and the complexity of prescription drugs will increase. Pharmacists can take advantage of this trend by expanding their activities in the management their patients' medication use. PMID- 1285555 TI - Computer planning, budgeting, and financial control. PMID- 1285556 TI - The clinical evaluation of balance disorders. PMID- 1285557 TI - Assessment and treatment of adenotonsillar hypertrophy in children. PMID- 1285558 TI - Obstructive sleep apnea: therapeutic alternatives. PMID- 1285559 TI - Pediatric endoscopy: anesthesia and surgical techniques. PMID- 1285560 TI - The management of peritonsillar abscess in the 90s: an update. PMID- 1285561 TI - Tricholemmal cysts of the head and neck. AB - PURPOSE: Tricholemmal cysts, sometimes termed pilomatrixomas, are benign skin neoplasms. This study was undertaken to evaluate the clinical experience with management of pilomatrixomas at a large, referral-based university hospital. PATIENTS AND METHODS: The records of patients treated at the UCLA Medical Center were reviewed retrospectively. Patients treated during the years 1966 to 1991 inclusive were reviewed for details of the clinical course. All pathology slides were confirmed histologically. RESULTS: Pilomatrixoma was confirmed in 53 patients. Of these, 29 patients (55%) had pilomatrixoma isolated to the head and neck region. All were treated with surgical excision. One patient (3%) experienced recurrence due to inadequate initial excision. Subsequent re-excision resulted in a cure. CONCLUSION: Tricholemmal cysts present as solitary, painless, slow-growing cutaneous nodules often resulting in discoloration of the overlying skin. Simple excision cures this benign neoplasm, and recurrences are rare. Fine needle aspiration biopsy may aid in the diagnostic workup. PMID- 1285562 TI - Water precautions in children with tympanostomy tubes. AB - PURPOSE: The necessity and effectiveness of taking precautions around water with children who have tympanostomy tubes is a source of some controversy among otolaryngologists. This study was undertaken to survey the practice standards of otolaryngologists treating these children. MATERIALS AND METHODS: A total of 1,266 board-certified otolaryngologists practicing (mean 14.8 years in practice) in the southern and eastern United States were surveyed to determine current recommendations. RESULTS: Among those surveyed, 13.1% forbid children with tympanostomy tubes from swimming, whereas 3.1% feel that no water precautions are needed. Limitations are placed in the depth of swimming by 68% and the type of swimming water by 18%. The most commonly recommended form of protection is the use of ear plugs, which is favored by 53.4%. Liberalization of recommendations concerning the need for water precautions was noted by 79% of respondents who cited personal experience as the single most influential factor. An overwhelming percentage of respondents indicated they would be willing to alter their current practice based on new information generated from a clinical trial. CONCLUSION: This survey demonstrates that diversity of opinion does exist among otolaryngologists relative to their recommendations for water precautions after placement of tympanostomy tubes. This survey demonstrates the need for a prospective randomized clinical trial designed to address this issue. PMID- 1285564 TI - Radiation osteitis of the facial bones. PMID- 1285563 TI - Lipid and volume analysis of neck drainage in patients undergoing neck dissection. AB - PURPOSE: We seek to establish normative values for the volume of postoperative neck drainage from patients undergoing ablative oncologic procedures that include a neck dissection and to analyze neck drainage for lipid content to establish guidelines that may be helpful in identifying chylous fistula when this diagnosis is not clinically straightforward. PATIENTS AND MATERIALS: Neck drainage obtained through continuous suction percutaneous drainage catheters was evaluated following 23 neck dissections performed on 19 patients. In every case, either radicle or modified type I neck dissection was performed. The volume of drainage was quantitated on a day-to-day basis. In a separate group of 27 patients undergoing neck dissection, neck drainage was compared with serum levels of triglyceride, cholesterol, and chylomicron content. RESULTS: The mean duration of neck drainage was 5 days. Maximum drainage (160 mL) was noted on the first day and dropped daily to less than 10 mL by the fifth postoperative day. A statistically significant difference between serum and neck drainage triglyceride and cholesterol content was observed in nearly all cases. Neck drainage fat content was lower than that noted in serum in nearly all cases. Chylomicron content of 4% was encountered in neck drainage. CONCLUSIONS: This study provides normative data on lipid content of neck drainage. With only a rare exception, the triglyceride and cholesterol levels are higher in the serum than in the neck drainage. A triglyceride level of 100 mg/dL seems to be the upper limit of normal (mean plus 1 standard deviation). A low level of chylomicron (> 4%) is consistent with normal healing and may be due to breakdown of fatty tissue. PMID- 1285565 TI - Laryngeal manifestations of Goldenhar syndrome. PMID- 1285566 TI - Allergy to latex. PMID- 1285568 TI - Reduced nonspecific bronchial reactivity and decreased airway response to antigen challenge in atopic asthmatic patients treated with the inhaled leukotriene D4 antagonist, L-648,051. AB - We studied the effect of the inhaled leukotriene D4 antagonist, L-648,051, on antigen-induced bronchoconstriction and nonspecific bronchial reactivity. Ten males with mild atopic asthma completed a double-blind, randomized, two-period, placebo-controlled cross-over study. For a 7-day period patients inhaled either placebo or 6 mg of L-648,051 four times daily. Bronchial reactivity to methacholine was measured at base line (day 1) and after 6 days, treatment (day 7). On day 8, after inhaling 6 mg of the antagonist (or placebo), the patients were challenged by inhaled antigen; they received an additional 6 mg of the antagonist (or placebo) 3 h later. Pulmonary function (forced expiratory volume in 1 s, FEV1) was measured serially through an 8-h post-antigen challenge. Nonspecific airway reactivity was again measured on day 9. Compared to placebo, L 648,051 treatment diminished the methacholine reactivity, on both day 7 (NS) and on day 9 (P < 0.05). In addition, the immediate and late bronchial responses to antigen challenge on day 8 were attenuated in the patients when treated with L 648,051. In the immediate phase (0-3 h postchallenge), the airway response was significantly reduced at all recordings between 20 min and 1 h postchallenge. In the late phase (3-8 h postchallenge), the pulmonary response was also reduced. However, the reduction was statistically significant only at the 5-h recording. The results suggest that sulfidopeptide leukotrienes are of importance for nonspecific airway reactivity, and that leukotriene D4 is a significant mediator in the immediate asthmatic reaction. PMID- 1285567 TI - IgE levels in faecal extracts of patients with food allergy. AB - IgE levels in faecal extracts (Copro-IgE levels) were investigated in food allergy (FA) patients before and after the challenge test administration of food allergens. IgE levels were measured by time-resolved fluoroimmunometric assay. In addition, the effects of administration of oral sodium cromoglycate (SCG) on the Copro-IgE levels were studied. Copro-IgE levels in patients with FA, who were placed on an elimination diet, did not differ from those of healthy children. After a challenge test immediate symptoms of urticaria and wheezing were observed in all FA patients. Copro-IgE levels in each patient increased markedly within 24 h of the challenge test. Moreover, FA patients treated orally with SCG showed neither the increase in Copro-IgE levels nor any remarkable symptoms after the challenge. Our results suggest that the increased Copro-IgE levels may be a specific consequence of the local immune response to food allergen stimulation in the gut mucosa. PMID- 1285569 TI - Histamine-induced inhibition of neutrophil chemotaxis and T-lymphocyte proliferation in man. AB - Histamine inhibits in vitro human neutrophil chemotaxis and T-lymphocyte proliferation via H2 receptors. The aim of this study was to verify these inhibitory effects of histamine in man in vivo. Healthy volunteers were challenged with histamine by intravenous (1 mg), subcutaneous (1 mg) and inhalatory (2.4 mg) routes. Venous blood was taken before and at different times after challenge. Neutrophil chemotaxis was studied by the Boyden assay and T lymphocyte proliferation by counting H3-thymidine incorporation in cultured mononuclear cells. Plasma histamine was measured by radioimmunoassay. Histamine infusion caused transient systemic symptoms as well as a significant decrease of neutrophil chemotaxis (mean - 26% +/- 6) and of PHA-pulsed T-lymphocyte proliferation (mean - 16% +/- 6) 4 h after histamine challenge. Subcutaneous injection of histamine caused only a significant decrease of neutrophil chemotaxis (mean - 24% +/- 15) 4 h after injection. Histamine inhalation was well tolerated and caused a significant depression of neutrophil chemotaxis (mean - 40% +/- 15) and of T-lymphocyte proliferation (mean - 27% +/- 6) 2 and 4 h after the challenge. Histamine challenges were always accompanied by a rapid and transient rise in plasma histamine. Inhalation of an H2 agonist (impromidine) but not of an H1 agonist (betahistine) caused a decrease of neutrophil chemotaxis and of T-lymphocyte proliferation. Oral pretreatment with an H2 antagonist (cimetidine) before histamine inhalation prevented histamine-induced decrease of neutrophil chemotaxis and T-lymphocyte proliferation, whereas astemizole, an H1 antagonist, had no effect. In conclusion, during the few hours following administration, exogenous histamine in man causes a depression of neutrophil chemotaxis and T-lymphocyte proliferation via H2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285570 TI - Elevated levels of peripheral-blood, naturally occurring aliphatic polyamines in bronchial asthmatic patients with active symptoms. AB - The levels of peripheral-blood, naturally occurring aliphatic polyamines, such as putrescine, spermidine, and spermine, from 21 bronchial asthmatic patients (11 atopics and 10 nonatopics) were measured by postcolumn derivatization high performance liquid chromatography analysis. None of the patients, except the 44 year-old woman in the case report below, were given prednisolone, and they were instructed to take only regular medication during the tests. Blood was drawn from the patients in a fasting state, and the polyamine levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Nine (5 atopics and 4 nonatopics), 6 (3 atopics and 3 nonatopics), and 4 (3 atopics and 1 nonatopic) out of 20 patients, when they had relatively mild asthmatic attacks, showed higher putrescine, spermidine, and spermine levels, respectively, than those of normal healthy control subjects. The levels of peripheral blood polyamines from a 44-year-old atopic bronchial asthmatic woman, who was admitted to the hospital with severe asthmatic attacks, were measured serially, and the putrescine and spermidine levels were found to be elevated during the asthmatic attacks, returning to normal levels in parallel with the clinical course. These data may suggest a role for naturally occurring aliphatic polyamines in bronchial asthma. PMID- 1285571 TI - Diurnal variation of urinary histamine and 1-methylhistamine excretion in healthy children. AB - In order to establish a noninvasive method of monitoring immediate hypersensitivity reactions in children, we studied the diurnal variation of urinary histamine and 1-methylhistamine excretion and the influence of food intake in a group of 14 healthy nonatopic children (aged 2-16 years). Histamine and 1-methylhistamine in spontaneous urine samples were determined by radioimmunoassay. Mean variation of 2-h intervals was much higher for urinary histamine than for 1-methylhistamine (45% of base-line level versus 24%). There was no circadian rhythm or influence of food intake. The short half-life of histamine released into blood circulation may be the main reason for the higher variation of histamine excretion. In children, urinary 1-methylhistamine is less influenced by diurnal variation and is therefore more suited to monitor immediate hypersensitivity reactions than urinary histamine itself. PMID- 1285572 TI - Clinical atopy and associated factors in primary-school pupils. AB - To investigate potential risk factors for clinical atopy in childhood, we obtained cross-sectional data from a cohort of 1376 8-year-old pupils. Parental atopy (hay fever, asthma, eczema), gestational age, maternal smoking habits, and the child's history of asthma, hay fever, and eczema were ascertained by questionnaire. Combining the history and the result of a skin prick test using seven aeroallergens, we defined the child's atopic diseases. Of the population evaluated, 25.4% were categorized as atopic (10.2% allergic asthma, 17.3% eczema, 6.9% hay fever). As compared with the clear nonatopics (40.2%), parental atopic diseases were more prevalent in each of the atopic groups. Significant associations of the parents' and child's disease were obvious for eczema and hay fever. Low gestational age (LGA) was more frequent in children with any atopy or with an allergic asthma (odds ratio (OR) 1.7; 95% confidence interval (CI) 1.02 2.97; OR 2.8; 95% CI 1.5-5.4). Hay fever and allergic asthma occurred less frequently in girls (OR 0.5; 95% confidence interval 0.3-0.8; OR 0.6; 95% CI 0.4 0.9). In conclusion, our data underline the importance of parental atopy for the clinical outcome in the offspring. In addition, LGA appears to be a risk factor for allergic asthma and for general atopy in later life. PMID- 1285573 TI - Occupational asthma in a hairdresser caused by persulphate salts. AB - Persulphate salts, which are common constituents of hair bleaches, have occasionally been reported to cause occupational asthma in hairdressers. We describe the clinical and immunological studies carried out in a hairdresser who developed cutaneous and respiratory symptoms, about 1 year after being employed in a hairdressing salon. Skin prick tests with 1:5 w/v potassium and sodium persulphate extracts were positive in our patient at 15 min and negative in control subjects. The European standard contactans (ECDRG) and a battery of hairdressing agents were patch tested with positive result to KATHON CG (isothiazolinone). The methacholine-inhalation test showed airway hyperresponsiveness. Bronchial provocation test with a 1:50 w/v potassium persulphate extract elicited a nonimmediate asthmatic reaction, followed by recurrent nocturnal fall in FEV1 lasting up to 3 days after the test. Plethysmography results revealed air trapping caused by a marked increase of airway resistance 3 h after the specific bronchial challenge. Histamine release test was not conclusive, and the determinations of specific IgA, IgM, IgG and IgG subclasses by EIA and IgE by RAST against persulphate salts were negative. PMID- 1285574 TI - Micellar catalysis in flow injection systems: the nitrosation reaction. AB - The use of aqueous micellar carrier streams in flow injection is shown to catalyse on-line reactions and thereby improve the sensitivity relative to non micellar systems. The effect of several different micellar systems on the nitrosation reaction of N,N-diethylaniline in acidic solution was investigated. The mechanism of the micellar enhancement is discussed and the sensitivities of the method in both aqueous and micellar media are compared. The presence of the cationic surfactant, cetyltrimethylammonium bromide, is shown to improve the sensitivity of the analysis. The effect of the micellar solution on the dispersion characteristics of the system was also studied. The greater viscosity of the micellar phase increases dispersion for non-reacting systems, but when monitoring a reaction product the increased reaction rate can counteract this and the micellar carrier can show less over-all dispersion than the aqueous carrier. PMID- 1285575 TI - Determination of thiocyanate in human saliva and urine by ion chromatography. AB - A simple ion-chromatographic method has been developed for the determination of trace amounts of thiocyanate in human saliva and urine. Thiocyanate separation and detection were carried out on an ODS column coated with cetyldimethylamine and by an ultraviolet detector, respectively. Citrate solution (1 mmol l-1) was used as the mobile phase. Thiocyanate was clearly separated from many organic and inorganic anions found in saliva and urine samples. The analytical results obtained by the proposed method agreed with those of the Fe(3+)-thiocyanate spectrophotometric method. Thiocyanate concentrations in the saliva and urine of smokers were found to be significantly higher than those of non-smokers. PMID- 1285576 TI - High-performance liquid chromatographic determination of fatty acid binding proteins in rat liver with fluorescence detection. AB - A highly sensitive, simple and reproducible method for the quantitative determination of fatty acid binding protein in rat liver by post-column high performance liquid chromatography with fluorescence detection is presented. Fatty acid binding protein in rat liver cytosols is separated by gel-permeation column chromatography, which is followed by fluorescence detection. The detection makes use of the fluorescence enhancement observed when a fluorescent fatty acid probe, dansylundecanoic acid, binds to fatty acid binding protein. The method is rapid, simple to perform and highly sensitive. The method was applied to the determination of fatty acid binding protein in liver from control and hypolipidaemic drug treated rats. PMID- 1285577 TI - Determination of femtomole concentrations of catecholamines by high-performance liquid chromatography with peroxyoxalate chemiluminescence detection. AB - A highly sensitive method for determination of the plasma catecholamines, norepinephrine (NE), epinephrine (E) and dopamine (DA) is described. The method consists of the extraction of the catecholamines, using 3,4-dihydroxybenzylamine as internal standard, from plasma with alumina (5 mg), followed by a reversed phase column separation, on-column fluorogenic derivatization with ethylenediamine (ED) and post-column peroxyoxalate chemiluminescent reaction detection utilizing bis[4-nitro-2-(3,6,9-trioxadecyl-oxycarbonyl)phenyl] oxalate (TDPO) and hydrogen peroxide. In order to optimize the reaction conditions for high-performance liquid chromatography to obtain highly sensitive detection, the effects of changing reagent compositions on the chemiluminescence yield were investigated. The following are the optimized conditions. Eluent, a mixture of 50 mmol l-1 potassium acetate (pH 3.20)-50 mmol l-1 potassium phosphate (pH 3.20) acetonitrile (90.15 + 4.85 + 3 v/v/v) containing 1 mmol l-1 sodium hexanesulfonate (40 degrees C) and flow rate, 0.5 ml min-1. Fluorogenic reagent solution, 105 mmol l-1 ED and 175 mmol l-1 imidazole in acetonitrile-ethanol (90 + 10 v/v) and flow rate, 0.25 ml min-1. Reaction coil (15 m x 0.5 mm i.d.) heated at 80 degrees C. Chemiluminogenic reagent solution, 0.25 mmol l-1 TDPO, 150 mmol l-1 hydrogen peroxide and 110 mmol l-1 trifluoroacetic acid in dioxane-ethyl acetate (50:50 v/v) and flow rate, 1.4 ml min-1. The detection limits for all the catecholamines were 1 fmol (signal-to-noise ratio at 2). The standard deviations of the method for the determination of NE, E and DA added to rat plasma (2.5 nM) were 3, 3 and 4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285578 TI - [A case of multiple arteriovenous fistulae in a postphlebitic syndrome of longterm evolution]. AB - Authors report a case of a 77-years-old man who, after an accident of traffic on 1968, presented a left ileo-femoral deep venous thrombosis. Consequently, the patient suffered and important postphlebitic syndrome, with several varicose packs which were treated by surgical procedure in other centre. During several years, patient presented severe trophic diseases. Seventeen years after the beginning of his pathology, and during an angiologic examination, multiple arteriovenous fistulas at the left ileofemoral area have been shown. An skeletalization was impossible because of the severe ulcerations of the leg; so a left iliac arterial ligature and a Dacron Banding in primitive iliac artery, reducing a 50% the diameter, were made. The postoperative result was excellent, with an spectacular reduction of the fistulous communications and a complete remission of the cutaneous ulcerations. PMID- 1285579 TI - [Intraoperative iliac angioplasty and distal revascularization: is it an efficacious method in the high-risk patient?]. AB - The fact that iliac femoro-popliteal areas are both simultaneously interested in some high risk patients, frequently is cause of several problems in the indication of the surgical treatment. So, we have decided to practice an iliac Angioplasty peroperatively as a method of iliac revascularization in association with the surgical repairment of the femoro-popliteal area. Results of 20 patients with 23 surgical procedures during a period of two years is reported. PMID- 1285580 TI - [Arterial embolisms in the upper and lower limbs: a clinical review]. AB - A clinical review about the subjects is made. Percentages and comparisons between lower and upper limbs were established. Correlation with statistics from other authors are presented. PMID- 1285581 TI - [The epidemiology and cost/effectiveness analysis of diabetic angiopathy in vascular surgery]. PMID- 1285582 TI - [Hemodynamic bases for the automated quantification of the degree of obstruction in the peripheral arteries of diabetic patients]. AB - In order to improve in the early diagnosis of an arterial occlusion, we proposed the bases of an automatized system that allows to recognize the hemodynamic features of diabetic patients in different stadiums of their disease. Fifty-four patients with type-II diabetes were studied. We recorded the arterial flow curves in the bilateral femoral, popliteal, pedia and tibial-posterior arteries from all of our patients. In the distal arteries from patients with hemodynamics disturbances, we found normal values of the variants measured: maximal systolic speed flow (Max A), maximal diastolic speed flow (Max D), Peurcelot's resistance (RP), pulsatility index (PI) and spectral band (SB). PMID- 1285584 TI - [Physical capacity and some determining factors in the patient with the postphlebitic syndrome]. AB - 40 limbs from normal persons and 32 limbs from patients with postphlebitic syndrome were studied. The latter group was classified according to the phlebography in partial and total recanalized postphlebitic groups. The research was carried out with a strain gauge plethysmograph and an ergometric bicycle. The patients showed the greater values of the venous volume, the maximal venous outflow and the rate of venous refilling, specially, the patients with total recanalized postphlebitic syndrome; this suggest a greater degree of venous valve insufficiency and a loss of the viscoelastic properties of venous vascular wall. The peripheral resistance was greater in the postphlebitic groups and it suggests a higher sympathetic nervous tone. The physical working capacity was lower in the postphlebitic patients and no relation was observed between it and the plethysmographic parameters. PMID- 1285583 TI - [The functional effect of internal carotid TEA on ocular hemodynamics]. AB - Fifteen patients with a stenosis of the internal carotid artery superior than a 70% were studied in order to analyze the effects of TEA on the ocular hemodynamics. Analysis was made by ophthalmodynamography and electrofunctional studies. An improvement of the ocular hemodynamics was found, particularly by ophthalmodynamography and visual evoked potentials. PMID- 1285585 TI - [Should Ofuji's papuloerythroderma be considered an individual entity?]. PMID- 1285586 TI - [Cleavage fragments of C3 and of dermo-epidermal junction of normal human skin]. AB - Recently, we have demonstrated the presence of C3dg deposits, a cleavage fragment of the third component of complement, on the basement membrane zone (MB) of normal human skin. These C3dg deposits are specific, isolated and not restricted to stratified squamous epithelia. Their origin is not thought to be due to passive incorporation of circulating C3dg within selected MB. Conversely, human keratinocytes are able to synthesize and secrete C3 and could represent a local source for these C3dg deposits. In situ production of C3 by epidermal cells could play a role in local inflammatory reactions. Similarly, a C3dg binding site(s) in selected basement membrane may account for the accumulation of C3-containing immune complexes in such tissues in pathological conditions. PMID- 1285587 TI - [Chronicity and diagnostic doubts of Melkersson-Rosenthal syndrome. Analysis of developing ways in 5 cases]. AB - In order to demonstrate the variability of the muco-cutaneous and neurovegetative signs and symptoms of Melkersson-Rosenthal syndrome (MRS), we report the cases of five out of 80 patients suffering from this complex oro-facial syndrome. In the majority of our patients the major symptoms, and in particular recurrent labial or intraoral swellings and/or facial palsy, did not occur simultaneously, which delayed the definite diagnosis of either complete or incomplete type of MRS. However, more than 80 p. 100 of our patients complained of various relapsing cranio-facial neurovegetative troubles that constitute the so-called minor symptoms of MRS, whereas a history or sequelae of facial palsy were found in only 35 p. 100 of our patients followed up for years or decades. In patients with solitary facial palsy or oro-facial oedemas as the initial symptom of putative MRS, the uncovering of concomitant minor symptoms proves to be helpful for substantiating the recognition of incomplete MRS. Thus, in questionable cases of MRS attention should be paid to seemingly incidental disturbances of the cranio facial neurovegetative system (e. g., relapsing disorders of lacrimation, sweating, migraine-like headache) forming minor but characteristic hints to incomplete or unusual cases of MRS. PMID- 1285588 TI - [Narrow-band UVB phototherapy (Philips TL01 lamps) in psoriasis]. AB - The authors report the results of an open study conducted on 53 patients with psoriasis treated by narrow-band UVB phototherapy, using Philips' TL01 lamp. With a simple procedure which did not require MED determination this treatment gave satisfactory results in 92 p. 100 of the cases, with mild burns in only 9 p. 100. The morphological type of psoriasis (patchy, guttate or nummular) had no influence on the therapeutic result, but the degree of infiltration of the lesions and their location on the lower limbs proved to be a factor of relative resistance. In most patients the results were obtained in 20 sessions with a mean cumulative dose of 20.19 +/- 2.7 J/cm2. Some patients had an additional treatment of 6 sessions. The results obtained with Philips' TL01 lamp were as satisfactory as those obtained with the conventional UVB lamps, but the TL01 lamp seemed to be easier to handle and better tolerated, which gives them some advantages over the latter. PMID- 1285589 TI - [Ofuji's papuloerythroderma: efficacy of interferon-alpha]. PMID- 1285590 TI - [Cutis marmorata telangiectatica congenita: crossed limb dimelia]. AB - We report a case of localized cutis marmorata telangiectatica congenita involving the right upper limb and the left lower limb. This is a rare distribution, with only one case in the literature. The patient, a 22-month old boy, showed no other abnormality. PMID- 1285591 TI - [Superficial disseminated porokeratosis with dermal amyloidosis]. AB - A case of non-actinic disseminated superficial porokeratosis with dermal amyloid deposits in a 53 year-old-man is reported. The lesions of the trunk and arms were typical, but annular lesions of the ankles were lichenoid. The amyloid deposits were present under the cornoid lamella in the typical lesions and absent in the annular lesions. The different clinical variants of porokeratosis are discussed. The origin of amyloidosis is debated; it seems to be epidermic, due to degeneration of the keratinocytes. The secondary cutaneous amyloidosis is usually described in association with epithelial tumors or psoriasis, but exceptionally with porokeratosis. PMID- 1285592 TI - [Acne and enthesiopathy during anti-epileptic treatment]. PMID- 1285593 TI - [Calcifying panniculitis]. AB - We report a case of calcifying panniculitis which occurred in a 67-year old woman suffering from chronic renal failure and primarily involved anticoagulant injection sites. Calcifying panniculitis is a rare condition belonging to the spectrum of calciphylaxis first described by Selye in 1962. This disease seems to imply necessarily a specific morbid background including renal failure together with calcium-phosphate metabolism impairment. Following the action of a so-called "challenger" (in the present case calcium heparinate [Calciparine], a subcutaneously administered anticoagulant drug), the lesions start as painful subcutaneous nodules soon turning into plaques of necrosis. The area involved mainly includes the abdomen and thighs, due to the preferential distribution of fat and the classical use of such regions for subcutaneous injections. In our patients, histological examination disclosed an initial involvement of subcutaneous fat vessels mimicking mediacalcosis, soon followed by calcium phosphate deposits within interadipocyte spaces. An electron microscopy study confirmed the presence of calcium crystals within the cytoplasms of some connective tissue cells and the extracellular matrix. From a review of the literature, it seems reasonable to normalize the calcium-phosphate product by reducing hyperparathyroidism as a first therapeutic step. Then, wide surgical excision of the necrotic areas should be performed to rule out any possibility of self worsening of the lesions and provide the best chance of healing without superinfection. The use of diphosphonates on pathophysiological grounds is discussed. PMID- 1285594 TI - [Erythroderma induced by teicoplanin]. AB - We report the case of a 38-year old man who developed erythroderma during treatment with teicoplanin for staphylococcal septicaemia. The clinical symptoms, which included high fever, shock and erythroderma, were suggestive of staphylococcal toxic shock. After teicoplanin was withdrawn and replaced by vancomycin the disease followed a favourable course. The reintroduction test was positive. This case illustrates the problems associated with the diagnosis of erythroderma in intensive care patients and confirms that it is possible to prescribe vancomycin in cases with allergic reaction to teicoplanin. PMID- 1285595 TI - [Fixed pigmented erythema caused by chlormezanone]. PMID- 1285596 TI - [A case for diagnosis dating from 1786]. PMID- 1285597 TI - [Adie's syndrome and "coup de sabre" scleroderma]. PMID- 1285598 TI - [Concerning the article: Bullous pemphigoid with negative direct immunofluorescence, does it exist? (Ann Dermatol Venereol 1992; 119:11-17)]. PMID- 1285600 TI - [A case for diagnosis: Crocker's dermatitis repens]. PMID- 1285599 TI - [Concerning the article: Confluent progressive hypomelanosis of the melanodermic junction. (Ann Dermatol Venereol 1992;119:19-24)]. PMID- 1285601 TI - [A case for diagnosis: zinc deficiency]. PMID- 1285602 TI - [Management of Gougerot-Sjogren syndrome]. PMID- 1285603 TI - [Photography in dermatologic practice]. PMID- 1285604 TI - [Systemic mastocytosis]. PMID- 1285605 TI - [Donor-recipient lung volume matching in double lung transplantation. Value of left lower lobe graft]. AB - For double lung transplantation, lung volume matching is easier comparing the predicted total lung capacities of the donor and recipient and the recipient's true TLC. The major concern in the inability to close the chest when the donor lungs are too large. The technique reported of left lower lobe implantation during bilateral single lung transplantation might be of great value in patients with small lung volume. PMID- 1285606 TI - [Establishment of a bank of cryopreserved valve homografts and clinical use in ninety-two patients]. AB - Good long-term results obtained with homologous valve grafts, specially for correction of congenital cardiac defects, prompted us to create a local cryopreserved homograft bank. A 5-year experience is described, including indications for harvesting, techniques of preparation, cryopreservation and thawing. During this period, 195 homografts entered the bank and 92 were used. Among these 92 clinical cases, 74 consisted of right ventricular outflow tract reconstruction (47 valved conduit and 27 monocusp bearing patch) and 17 were left ventricular outflow tract reconstructions (11 free hand aortic valve and 6 aortic root replacement). Only one case was a tricuspid replacement with a stented homograft. Short-term results, with these homografts, are satisfactory and are compared with long-term results reported in the literature. The authors insist on using very thorough techniques and constant quality control. New developments should include viability control and immunological studies. PMID- 1285607 TI - [The internal mammary artery binds more 125I-albumin than the aorta]. AB - The internal mammary artery is currently the arterial replacement of choice for coronary artery bypass grafts. The authors studied the permeability of the vessel wall of the internal mammary artery and the ascending aorta in 12 patients undergoing coronary artery bypass grafts by comparing the 125I-albumin binding profiles. Their results suggest that albumin crosses the internal mammary artery more easily than in the aorta. PMID- 1285608 TI - [Traumatic rupture of the aortic isthmus revealed by acute obstruction of the descending thoracic aorta]. AB - A traumatic transection of the upper descending thoracic aorta, undiagnosed, was complicated on the tenth day by an acute obstruction of the descending thoracic aorta. The upper body hypertension resulted in generalised convulsions and cardiac failure with pulmonary oedema. The lower body ischemia resulted in paraplegia, acute ischemia of the lower limbs, liver failure and anuria. An emergency revascularisation of the lower body was achieved by axillary-bifemoral bypass. The improvement of the clinical status allowed complete repair of the aortic transection two days after the extra-anatomic revascularisation. This case emphasizes the severity of the cases with impaired blood flow to the lower body and the benefit of the extra-anatomic bypass in pathology of the upper descending thoracic aorta when complete repair of the aortic transection is associated with an extremely high risk. PMID- 1285609 TI - [Traumatic double rupture of the isthmic aorta. Apropos of an unrecognised case successfully treated by two-stage surgery]. AB - The authors report the case of a 33 year old patient, who underwent an emergency repair of a traumatic tear of the thoracic aorta, after a car accident. This operation was carried out with femoro-femoral cardiopulmonary bypass support. Associated lesions were traumatic tear of the left diaphragm repaired through left thoracotomy during repair of the aorta, rupture of the liver and multiple fractures of the left superior limb. Postoperative course was marked by liver hemorrhage and septicemia. Orthopedic treatment of the various fractures was performed. The course of thoracic lesions was uneventful. An aneurysm of the aortic isthmus was revealed during venous digital subtraction angiography routinely performed 60 days after surgery. The patient was reoperated with femoro femoral bypass support. A second incomplete tear of the aorta, missed during the first operation was discovered 3 cm above the suture of the first one. This lesion was easily repaired and the post-operative course was uneventful. The value of systematic control angiography after aortic traumatic repair is emphasised. PMID- 1285610 TI - [Postoperative acute aortic dissection. Apropos of two cases]. AB - Aortic dissection after cardiac surgery is a rare complication. The prognosis is often poor: 33-78% of mortality. The study of two cases out of 2100 patients operated upon during the last three years, and the review of the literature, allows to recall the mechanism, the anatomic origin and the different surgical techniques. Early diagnosis is essential. Some preventive techniques may reduce the incidence of the iatrogenic dissections. PMID- 1285611 TI - [Total anomalous pulmonary venous return in a 61 year-old adult]. AB - The authors report a case of total anomalous pulmonary venous return successfully treated by surgery in a 61 year-old man. This case is unusual because of the late discovery of this congenital malformation which is usually rapidly fatal in the absence of surgical correction. This prolonged survival can be explained by the large atrial septal defect and the absence of obstruction, to pulmonary venous return and associated malformations. Surgical repair is essential to prevent the development of irreversible lesions of the right side of the heat and the pulmonary arterial bed. PMID- 1285612 TI - [Radiation-induced sternal tumors: value of myocutaneous flap of the latissimus dorsi]. AB - Two patients treated by radiotherapy, one 13 years previously for Hodgkin's thymoma and the other 10 years previously for breast cancer, presented with a radiation-induced sternal tumour. The first case had undergone manubriectomy for fibrosarcoma complicated by dehiscence of the skin wound one year prior to referral to our unit: she presented with a haemorrhagic ulcerated recurrence. The lesions were widely excised (skin defect: 13 x 13 cm). The second patient underwent "en bloc" cutaneo-osteomyopericardectomy with omentoplasty onto the pericardium and sternal prosthesis (skin defect: 12 x 7 cm). These tumours are rare, but the radiation-induced skin damage requires wide excision. In both cases, the skin defect was easily repaired by means of a latissimus dorsi myocutaneous flap. PMID- 1285613 TI - [Lobectomy extended to the main bronchus in the treatment of bronchial cancer (seventy-three cases)]. AB - Sleeve allow excision of bronchial carcinoma in patients not able to functionally tolerate pneumonectomy. Our series consists of 73 patients operated over the last thirty years. Implantation of the bronchus was treated either by wedge resection or by complete resection followed by reimplantation. This procedure was performed for respiratory functional reasons in 39 cases (53%), on principle in 27 cases (37%) and in palliative indications in 7 cases (10%). The high perioperative mortality (6.8%) and morbidity (20%) were related to bronchovascular complications which were eliminated over the last decade. Local recurrences (23%) were more frequent than following conventional resections. On the other hand, the survival, 80% at one year, 62% at 2 years, 54% at 3 years and 39% at 5 years, related more to metastatic dissemination than to local recurrence, was comparable to that of the control group of pneumonectomised patients. This procedure gave identical results in terms of survival, but should be reserved for patients with respiratory failure due to the increased risk of local recurrence. PMID- 1285615 TI - [Endobronchial neurogenic tumors]. AB - Endobronchial neurogenic tumours are exceptional and little known. The authors report two cases of such tumours: a neurofibroma of the right main bronchus in a 32 year old man and a schwannoma of the left main bronchus in a 10 year old child. Pneumonectomy was necessary in both cases due to destruction of the pulmonary parenchyma distal to the obstruction. The incidence of this type of tumour is estimated to be between 0.2 and 4%. They may be either schwannomas or neurofibromas, the discovery of which always raises the problem of the possible association of von Recklinghausen's disease malignant forms, neurogenic sarcomas or malignant schwannomas may also be encountered. The diagnosis is based on endoscopy which reveals the tumour and allows biopsy. Treatment of these essentially benign tumours should be conservative, provided the diagnosis is made early, prior to parenchymal destruction. The prognosis is poor in the malignant forms and chemotherapy may be useful in malignant schwannomas. PMID- 1285614 TI - [Non-malignant esophagotracheal fistulas in adults. Experience with 35 cases]. AB - Esophagotracheal fistula always constitutes a serious, life-threatening complication. Fistulae occurring during medical intensive care with mechanical ventilation are currently the most frequent. Their diagnosis was strongly suspected by clinical examination of the patient, but was always confirmed by endoscopy which revealed their exact site in relation to the vocal cords or carina, essential information for the choice of incision when it is decided to perform surgery. Twenty-five patients were treated medically. Treatment was always combined with gastrointestinal resting, control of gastro-oesophageal reflux and broad-spectrum systemic antibiotics. There were 19 deaths and 6 fistulae closed spontaneously. Three of these 6 patients developed a secondary tracheal stenosis, 2 of which were treated surgically by resection-anastomosis. Ten fistulae were closed surgically with a good long-term result. The indication for surgery was essentially based on the patients general and infectious status and on his or her respiratory autonomy. Technically, we always combined direct suture of the two organs with interposition of muscular or pleural tissue. PMID- 1285617 TI - [Injection of collagen in recurrent paralysis after thoracic surgery]. AB - The author describes a new technique of treatment of recurrent laryngeal nerve paralysis by intra-cordal injection of collagen after thoracic surgery. After description of the collagen used and the technique of injection, the author presents the results. It is a new method, simple, efficient, well tolerated, giving patients a voice, and treating their swallowing troubles. PMID- 1285616 TI - [Pseudotumoral thoracic actinomycosis with lung and brain metastases. Apropos of a case. Review of hundred thirty one cases in the literature]. AB - One particular case of thoracic actinomycosis is reported. The patient presented with a neurological picture mimicking a metastasis, as chest radiogram and CT Scan indicated a primary pulmonary tumor. Diagnosis of actinomycosis was overlooked and final diagnosis was based on direct microscopy of lung tumor, which required a thoracotomy, without any resection. Antibiotic treatment with penicillin was successful as the cerebral lesion was completely cured within 2 months and the thoracic lesion reduced 2/3rd volume within the same delay. The importance of correct handling of tissue specimens and adequate informations to the microbiologist are emphasized. Another point of interest is that good clinical results can be expected from prolonged antibiotic treatment. Surgery must be reserved for diagnosis if no other means has been effective, for failure of medical treatment or for acute complications. PMID- 1285618 TI - [Value of limited resections in the surgical treatment of lung cancers]. AB - From 1969 to 1990, 88 limited lung resections were performed for the treatment of malignant lung tumours. These operations consisted of 73 typical resections (29 segmentectomies, 15 bisegmentectomies, 23 middle lobectomies, 6 lingulectomies) and 15 atypical resections. In 15 cases, they were completed by lymph node dissection. These operations were performed in patients with a mean age of 55.8 years (range: 24 to 76). The ventilatory functional status contraindicated wider resection in only 7 cases. The immediate postoperative mortality (7 cases, i.e. 8%) and the postoperative complications observed in 29.6% of cases were higher than those observed after wide resections, but do not constitute a specific argument in the indication for partial resection. Histological examination of the operative specimens revealed 80 primary lung cancers (42 squamous carcinomas, 28 adenocarcinomas, 8 anaplastic and unclassifiable tumours, 1 bronchiolo-alveolar tumour and 1 malignant carcinoid tumour). The primary nature of the tumour could not be definitely confirmed in the other 8 patients (history of head and neck neoplasm in 7 cases and bladder carcinoma in 1 case). The survival according to TNM stage, histological nature of the tumour, positivity of the resection margins and intraoperative tumour effraction was identical to that associated with lobectomies. PMID- 1285619 TI - [Forgotten mediastinal goiter: seven cases]. AB - The authors relate their experience with 7 cases of mediastinal goiter residual to a subtotal thyroidectomy for substernal goiter. The differential diagnosis with ordinary recurrence was based on the absence of connection with the cervical remnant. The reasons for surgical decision-making was mediastinal compression in 4 patients, hyperthyroidism in 1 patient and absent diagnosis in 1 patient; surgery was systematic in 1 asymptomatic patient. Sternal splitting incision was required in 6 patients: alone in 3, associated with cervical incision in 3 others; excision by an exclusively cervical route was possible in one patient. No malignancy was discovered. Postoperative outcome was uncomplicated in all patients. The residual goiter has the same clinical and paraclinical presentation as the ordinary intrathoracic goiter; treatment should be principally surgical for the same reasons. Nevertheless, for this mediastinal tumor, sternum-splitting incision will be required in most cases. PMID- 1285620 TI - [Cystic tumor of the mediastinum of digestive origin. Apropos of a new case. Diagnostic and pathogenic hypotheses]. AB - An incidental discovery of a posterior and inferior mediastinal cyst-like opacity allowed us to diagnose a pulmonary sequestration in a 45-year old woman. The operative findings showed an hour-glass tumor of the inferior mediastinum with an abdominal prolongation attached by a stalk onto the top of the stomach. These findings made us change our diagnosis in favour of an abdomino-thoracic gastric duplication. This new hypothesis was not confirmed by the results of the pathological report which revealed two kinds of tissue; intestinal in the abdomen and broncho-pulmonary in the chest. Two diagnoses where then proposed: complex hamartoma or mediastinal bronchogenic cyst. The pathogenic interpretation in such cases is still very controversial. English authors are prone to classify them as broncho-pulmonary foregut malformations. Macroscopic and microscopic data of the specimen led us to consider our case-report to be a foregut malformation. PMID- 1285621 TI - [Prophylaxis of infectious endocarditis]. PMID- 1285622 TI - [Early hospital discharge after uncomplicated myocardial infarction: strategies]. AB - Considerable advances have been seen in recent years in the diagnostic and therapeutic management of myocardial infarction. Furthermore, approximately 50% of patients hospitalised for a myocardial infarction have shown no evidence of any complication by the 3rd day of the disease. With this in mind, the authors show that early discharge from hospital at the end of the first week is possible in perfect safety for the majority of these patients, most often treated by thrombolysis, based upon precise knowledge of the severity of arterial disease and of left ventricular function, and the detection of any residual ischemia or possible rhythm disturbances. Only patients with three vessel disease have a higher risk of residual angina and should theoretically be excluded from such programmes. Ambulatory rehabilitation is an essential adjuvant, contributing to a faster return to work and a decrease in health care costs. PMID- 1285623 TI - [Left ventricular relaxation and hypertension. Effect of captopril on gamma angiographic parameters]. AB - In order to evaluate the action of captopril on left ventricular filling in hypertension, 14 hypertension (158 +/- 10/101 +/- 5 mmHg) patients aged 51 +/- 6 years were investigated by Technetium 99m gamma-angiography. The time/activity curve was used to determine the maximum filling rate (MFR) and maximum filling time (MFT) of the ventricle before and after treatment with captopril (mean dose : 44 +/- 26 mg/day for 7 months). Blood pressure was significantly lowered by treatment and there was a decrease in left ventricular mass from 128 +/- 17 to 118 +/- 15 g/m2 (p = 0.07). Maximum filling rate was accelerated by treatment from 2.27 +/- 0.57 to 2.57 +/- 0.43 VTD . s-1, p = 0.005). This variation was due essentially to half of the patients, suggesting an "all or nothing" type response. Maximum filling time did not vary. The basic question raised by this type of study is to know whether the improvement in the available relaxation parameter, MFR, was associated with actual improvement in filling, which is the true aim. Although the explanations offered for the observed findings are hypothetical, taking into account of all the trial data together with the morphological data provided by echocardiography suggests that captopril does have an actual and hemodynamically significant action on filling. PMID- 1285624 TI - [Slow ventricular tachycardia caused by naftidrofuryl overdose (naftidrofuryl and ventricular tachycardia)]. AB - Treatment with intravenous naftidrofuryl may be complicated by ventricular arrhythmias. A case of slow ventricular tachycardia occurring in a 65-year-old man with a dilated cardiomyopathy following an accidental overdose of naftidrofuryl (2 x 200 mg ampules in 250 ml of 5% glucose solution in 2 hours) prescribed for complicated arterial disease of the lower limbs is reported. This sustained ventricular tachycardia converted spontaneously after several hours. This case emphasises the risk of arrhythmogenic effects of this drug and indicates the need for careful monitoring when it is used intravenously in patients with underlying heart disease. PMID- 1285625 TI - [Primary leiomyosarcoma of the pulmonary artery. Apropos of a case. Review of the literature]. AB - A 59-year-old woman hospitalised because of dyspnea and a heart murmur in a context of pyrexia was found to have evidence of obstruction of the pulmonary arterial system, clearly defined by ultrasonography, catheterisation and angiography and Imatron scan. The particular feature of this fifth reported case of pulmonary artery leiomyosarcoma is its documentation by transesophageal ultrasonography and tumor biopsy during catheterisation. Surgery with partial excision of the tumor was followed by survival for 6 months, bearing in mind the absence of chemo- or radiosensitivity of this type of tumor. Cases from the literature are reviewed. PMID- 1285626 TI - [Cerebral abscess disclosing congenital heart disease]. AB - Cerebrovascular accidents and brain abscesses are the most worrisome complications of cyanogenic cardiac lesions in infants and young children, but remain rare in the adult. The authors report the case of a brain abscess which led to the subsequent discovery of a congenital cardiac malformation consisting of a ventricular septal defect and moderate pulmonary valve stenosis. Complete correction of the cardiac lesions was carried out three months after neurosurgical treatment (needle biopsy/drainage). PMID- 1285627 TI - [False aneurysm of the left ventricle during the acute phase of myocardial infarction: diagnosis by transesophageal echocardiography]. AB - The authors report a case of myocardial infarction complicated by a false aneurysm of the posterior wall of the left ventricle, the diagnosis of which was confirmed, for the first time, by transesophageal echocardiography (TEE) which provided better definition of the anatomical features of the lesion: visualisation of the particularly wide neck (5 cm) and the site of rupture of the myocardium; demonstration of the presence in the false aneurysm with a thin pericardial wall of a large thrombus of different acoustic density, itself overlain by swirling whorls. Colour Doppler combined with TEE clearly showed the acceleration of flow at the neck and its slowing in the newly formed cavity. Once the diagnosis was made, the patient rapidly underwent surgery with a successful outcome. The quality of the images obtained without risk by TEE suggests the important role which this investigation could play in the future in the diagnosis of certain mechanical complications of myocardial infarction. PMID- 1285628 TI - [Arteriovenous fistula following surgery of intervertebral disk]. AB - Vascular damage during intervertebral disc surgery is uncommon. It sometimes leads to the formation of an arteriovenous fistula and about one hundred cases have been reported in the literature. The diagnosis is often early, with signs of venous hypertension predominating. The authors report a case of arteriovenous fistula presenting late as apparently primary congestive cardiac failure. The mechanisms of this condition were demonstrated during preoperative instrumental manoeuvres. Surgical correction is the only treatment alternative. Repair must be arterial and venous, most often using prosthetic material. This generally enables total and permanent recovery, but overall mortality in pathology of this type is not nil. PMID- 1285629 TI - [Right ventricular dysplasia]. AB - Arrhythmogenic right ventricular dysplasia is responsible for ventricular tachycardia affecting an apparently healthy heart. It can sometimes lead to sudden death, which may be the presenting symptomatology of the disease. It results from fibro-adipose infiltration of the free wall of the right ventricle, and sometimes of the septum, possibly secondary to myocarditis. The prognosis depends upon the quality of the left ventricle. If it is healthy, the only risk is that of arrhythmia. Treatment using anti-arrhythmic drugs is most often effective and, with proper management, the prognosis is good and the risk of sudden death eliminated. If the left ventricle is abnormal, there is the risk that dysplasia associated with arrhythmia will progress to right then congestive cardiac failure in the context of a dilated idiopathic cardiomyopathy with ventricular tachycardias originating on the right side. Arrhythmogenic right ventricular dysplasia is a notable cause of sudden death in athletes. Routine screening of such individuals is justified, as is that of those with high risk occupations (locomotive and vehicle drivers, etc.). PMID- 1285630 TI - [Combination of oral administration of cibenzoline and digoxin in patients with supraventricular arrhythmia]. AB - Chronic co-administration of digoxin and several antiarrhythmic drugs increases digoxin plasma levels. To determine the effects of the administration of oral cibenzoline on digoxin plasma levels and its effects on clinical and electrocardiographic parameters, we conducted a prospective multicenter study in 22 cardiac patients with a mean age of 66 +/- 12 years (39-85), who were on long term digoxin therapy (0.25 mg once daily for at least 2 weeks) and who required oral cibenzoline therapy in the prevention of recurrence of symptomatic atrial tachyarrhythmias. Cibenzoline was given for 4 weeks at a dose of 130 mg twice daily in patients aged less than 70 years (group I, n = 15) and this dosage was reduced by half in patients over 70 years of age (group II, n = 7). Evaluation of the effects of this combination on clinical and electrocardiographic tolerability as well as the drawing of blood samples for assay of cibenzoline and digoxin took place before and after 4 weeks treatment with cibenzoline. The digoxin plasma levels were (mean +/- sem) 0.96 +/- 0.1 ng.ml-1 before cibenzoline administration and remained unchanged after 4 weeks of combination therapy (1.0 +/- 0.1 ng.ml 1), p > 0.05. Digoxin plasma levels in group I varied from respectively 0.8 +/- 0.1 ng.ml-1 (0.5-1.7) to 0.8 +/- 0.1 ng.ml-1 (0.4-1.5) and in group II from 1.2 +/- 0.2 ng.ml-1 (0.6-2) to 1.4 +/- 0.3 ng.ml-1 (0.7-2.5). This therapy was well tolerated in 16 patients out of 21 evaluable patients (76%) and there was no significant change in vital signs during the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285631 TI - [Efficacy and tolerance of propafenone in the prevention after a year of recurrent atrial arrhythmia. Results of a multicenter study of 114 patients]. AB - One hundred and fourteen patients were included in an open multicenter trial of the prevention of atrial arrhythmias by propafenone and of the tolerability of this anti-arrhythmic agent after a year. The study population was divided into two groups: group I of 45 patients with only runs of arrhythmias and group II of 69 patients with a stable arrhythmia. Patients were seen again after 2 weeks, 3 and 6 months and 1 year. Holter records were obtained routinely in group I and at 6 months in group II. Treatment was stopped for inefficacy in 30 patients (10 of group I, 20 of group II), for intolerance in 10 patients (5 in each group) and for both in 3 patients (1 in group I, 2 in group II). Propafenone was considered to be effective and well tolerated in 55 per cent of patients, this success rate being identical in the two groups. Effectiveness persisted in a stable fashion at 1 year in those patients who responded initially. PMID- 1285632 TI - [Findings of bile duct ultrasonography in 100 patients with AIDS in black Africa]. AB - A systematic study of bile ducts by abdominal echotomography on 100 African patients affected by AIDS disease has showed 11 bile ducts abnormalities (7 alithiasic cholecystitis and 6 inflammatory cholangitis, associated in 2 cases). The patients studies showed several associated infections, particularly a pulmonary tuberculosis and/or extra-pulmonary. The etiology of bile ducts attack has not been formally specified: lack of Cryptosporidium at the stools parasitologic exam, but presence of several opportunistic germs, or no, in the several samples (blood, cerebrospinal fluid, stools, expectoration). PMID- 1285633 TI - [Exudative enteropathy in disseminated lupus erythematosus]. AB - We present the case of a young woman with a protein-losing enteropathy occurring in the context of systemic lupus erythematosus. This rare complication has limited gastro-intestinal manifestations and must be systematically looked for when hypoalbuminemia occurs in the absence of a lupus nephritis. High dose corticosteroids therapy (> or = 1 mg/kg/day of prednisone) usually leads to recovery, and should be the first treatment attempted. If this treatment is ineffective, bolus injections of methylprednisolone (1 g/day for three days) may be recommended. Immunosuppressive therapy should be given only if the above treatments are ineffective, or in case of cortico-dependency. PMID- 1285634 TI - [Bacterial ecology of the digestive tract and defense of the body]. AB - The indigenous microflora of the upper digestive tract is poorly developed and consists of microorganisms in transit, originating in the oro-pharynx. Aerobic bacteria, mainly streptococci, predominate. In the normohydrochloric stomach, the mean fasting bacterial concentration is 10(3)-10(4)/ml gastric juice. In the small intestine, levels of up to 10(5) bacteria/ml contents are reached. The essential mechanism which maintains this relative sterility of the upper digestive tract is the gastro-intestinal transit and in particular the interdigestive migrating motor complex. In the terminal ileum, a zone subject to relative stasis, the intraluminal bacterial population rises to 10(8)/ml in one third of subjects, with the appearance of enterobacter and strict anaerobes. In the colon, a zone of physiological stasis, the number of microorganisms per ml of contents is 10(8)-10(9) on the right side and 10(10)-10(12) on the left side. The dominant flora is strictly anaerobic and the subdominant flora optionally aero anaerobic, consist mainly of Enterobacter, Streptococci and Lactobacilli. The balance between the species of microorganisms in the colonic ecosystem and its stability results primarily from microbial antagonisms. The barrier flora, consisting of groups of anaerobes, either prevent the implantation of exogenous microorganisms (drastic barrier) or limit it to the subdominant flora (permissive barrier). The repression of the subdominant flora by the dominant flora prevents the subdominant flora from spreading to the mesenteric ganglia and then the whole body. Rupture of the barrier flora by a wide-spectrum antibiotic may permit the local multiplication of a pathogenic organism (C. difficile, Salmonella), or the spread of an opportunist organism (Klebsiella pneumoniae). PMID- 1285635 TI - [Digestive lesions in acute intestinal infections]. PMID- 1285637 TI - [Should travelers' diarrhea be prevented and/or treated?]. AB - The prevention of traveller's diarrhea should be limited to the evaluation of drinking water, the avoidance of certain foods and careful hygiene of the hands. Although their efficacy is somewhat controversial in this context, these precautions at any event reduce the risk of acquiring other feco-orally transmitted diseases. Because of the increasing resistance of the bacteria responsible and their multiplicity, early treatment of any actual case of traveller's diarrhea is preferable to prophylactic antibiotics. Therapeutic indications vary according to the severity of traveller's diarrhea and the general condition of the patient. Travellers must be aware of these considerations before their departure. PMID- 1285636 TI - [Food poisoning outbreaks: an epidemiological study]. AB - The occurrence of foodborne disease outbreaks (FDO) is increasing in industrialized countries. Most of these outbreaks (2/3) are notified from restaurants and other commercial establishments but more and more from households. Salmonella is the major agent of FDO, especially S. enteritidis for five years. However, its role may be overestimated because inadequate microbiological techniques routinely performed. Despite recent progress, several outbreaks still go unnoticed. Every outbreak should be early investigated, with methodical collection of clinical, bacteriological and food data, followed by statistical analysis. Once identified the responsible pathogen, the contaminated food, the source of contamination and the bacterial growth enhancing factors, rapid control measures can prevent further epidemics. Compulsory notification of all FDO to the public health services is the condition for the reliability of a national surveillance programme. PMID- 1285638 TI - [Action of acetorphan, an enkephalinase inhibitor, in acute diarrhea]. PMID- 1285639 TI - [The intraluminal transport of vitamin B12]. AB - Since the existence of vitamin B12 was suggested by Castle in the first few decades of this century, vitamin B12 has been the subject of many studies which have proved the high complexity of its assimilation by the organism. Over the last few years the marked progress in functional digestive exploration methods and the physical and the chemical characteristics of biological molecules have revived the established idea of the vitamin's intraluminal transit. Our recent studies have been concentrated on the bilio-duodenopancreatic stage of the vitamin B12 transport. In nature, vitamin B12 is only exceptionally met in its free form, it is always associated with a binder. Like a ball being passed from one player to another it moves between binders. Alimentary vitamin B12 released from its protein complexes by culinary preparation and gastric secretions, is combined with haptocorrin. In the duodenum the transfer of B12 on intrinsic factor is due to partial degradation of haptocorrin by pancreatic enzymes and intraluminal pH balance. Then combined with intrinsic factor the vitamin can be caught by the ileal receptor. The partial degradation haptocorrin joins vitamin B12 analogs from excreted bile or synthesized by the intestinal microorganisms. PMID- 1285640 TI - The Lipomycetaceae, a model family for phylogenetic studies. AB - The Lipomycetaceae (Endomycetales) are known from the genera Dipodascopsis, Lipomyces and Zygozyma with budding anamorphic states in Myxozyma. The family is easily recognized culturally and physiologically but is phenotypically and ecologically extremely diverse. This natural taxon is phylogenetically distinct from the Saccharomycetaceae, but probably related to the Dipodascaceae. The possible evolution of the lipomycetaceous anamorphs is discussed. PMID- 1285641 TI - Evidence for, and taxonomic value of, an arachidonic acid cascade in the Lipomycetaceae. AB - By using specific inhibitors of the lipoxygenase and cyclo-oxygenase pathways, arachidonic acid metabolites with similar sensitivities towards these inhibitors as in humans, were detected in Dipodascopsis uninucleata. The taxonomic value of aspirin sensitive arachidonic acid metabolites in the Lipomycetaceae was next assessed. No metabolites of which the production is inhibited by aspirin were detected in strains representing the following species: Lipomyces starkeyi, Lipomyces kononenkoae, Lipomyces tetrasporus, Myxozyma melibiosi, Myxozyma mucilagina, Myxozyma kluyveri, Waltomyces lipofer, Zygozyma oligophaga and Zygozyma arxii. The detection of such aspirin sensitive arachidonic acid metabolites in representative strains of Lipomyces anomalus and the genus Dipodascopsis, emphasises the isolated position of these taxa in the genus Lipomyces and the family Lipomycetaceae, respectively. Finally using long chain fatty acid analyses, electrophoretic karyotyping and other phenotypic characters, a phylogenetic scheme is proposed for some genera in the Lipomycetaceae. PMID- 1285643 TI - Clavispora opuntiae and other yeasts associated with the moth Sigelgaita sp. in the cactus Pilosocereus arrabidae of Rio de Janeiro, Brazil. AB - Clavispora opuntiae was the prevalent yeast associated with the feeding sites of Sigelgaita sp. larvae in the cactus Pilosocereus arrabidae. Also associated with this habitat were Candida sonorensis, Pichia cactophila, Pichia barkeri, Candida sp. A, Geotrichum sp., Geotrichum sericeum and the yeast like organisms Prototheca zopfii and Acremonium sp. Atypical yeast biotypes that may represent new species of Pichia, Sporopachydermia and Candida were isolated. Mating types of Clavispora opuntiae were at a ratio 70 h- to 3 h- and reduced levels of sporulation suggested low pressure for sexual reproduction in this habitat. Sigelgaita sp. probably was not an important vector for Clavispora opuntiae because it was not isolated from an adult or eggs of this moth. PMID- 1285642 TI - Myxozyma neotropica sp. nov. (Candidaceae)--a new yeast species from Costa Rica. AB - Two strains of an undescribed, soil-borne species of the genus Myxozyma were recovered. They differ from other accepted species of this genus in their carbon assimilation pattern, mol% G+C and low extent of DNA complementary. A description of the new species, Myxozyma neotropica, and a key to the species accepted in the genus are given. PMID- 1285644 TI - Evaluation of two unstructured mathematical models for the penicillin G fed-batch fermentation. AB - The mathematical model for the penicillin G fed-batch fermentation proposed by Heijnen et al. (1979) is compared with the model of Bajpai & Reuss (1980). Although the general structure of these models is similar, the difference in metabolic assumptions and specific growth and production kinetics results in a completely different behaviour towards product optimization. A detailed analysis of both models reveals some physical and biochemical shortcomings. It is shown that it is impossible to make a reliable estimation of the model parameters, only using experimental data of simple constant glucose feed rate fermentations with low initial substrate amount. However, it is demonstrated that some model parameters might be key factors in concluding whether or not altering the substrate feeding strategy has an important influence on the final amount of product. It is illustrated that feeding strategy optimization studies can be a tool in designing experiments for parameter estimation purposes. PMID- 1285645 TI - Characterization of a novel enzyme, N6-acetyl-L-lysine: 2-oxoglutarate aminotransferase, which catalyses the second step of lysine catabolism in Candida maltosa. AB - A novel aminotransferase catalyzing the second step of lysine catabolism, the oxidative transamination of the alpha-group of N6-acetyllysine, was identified and characterized in the yeast Candida maltosa. The enzyme was strongly induced in cells grown on L-lysine as sole carbon source. Its activity was specific for both N6-acetyllysine and 2-oxoglutarate. The Km values were 14 mM for the donor, 4 mM for the acceptor and 1.7 microM for pyridoxal-5-phosphate. The enzyme had a maximum activity at pH 8.1 and 32 degrees C. Its molecular mass estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis was 55 kDa. Since the native molecular mass determined by gel filtration was 120 kDa, the enzyme is probably a homodimer. PMID- 1285646 TI - High-affinity oxygen uptake by Bifidobacterium bifidum. AB - Oxygen uptake by washed cell suspensions of Bifidobacterium bifidum DSM 20082 was studied by using spectrophotometric measurements of the degree of oxygenation of added myoglobin as a measure of the concentration of dissolved O2. The absorbance changes during consumption of O2 in a closed reaction vessel were analysed by computer to obtain estimates of the changes in dissolved O2 concentration with time. These were then used to calculate the rate of O2 uptake as a function of the dissolved O2 concentration. The cell suspensions showed Michaelis-Menten kinetics with an apparent Km value of 0.06 microM O2. Cell-free extracts contained a soluble NADH oxidase activity with a stoichiometry corresponding to the reduction of O2 to H2O and with a high affinity for O2. PMID- 1285648 TI - Mechanism of chlorpromazine binding by gram-positive and gram-negative bacteria. AB - Chlorpromazine forms charge-transfer complexes with xanthene dyes in bacteria. These complexes permit the differentiation of Gram-positive and Gram-negative bacteria in both light and polarization microscopy. The birefringence induced by the charge-transfer complex might explain the molecular basis of bacterial staining. The charge-transfer complexes formed between chlorpromazine and xanthene dyes accumulate in the bacterial cell, mainly inside the bacterial cell wall. The complexes give the cells a color, which depends on the chemical composition of the staining structure, and in particular the polysaccharides of the cell wall in bacteria. Metachromatic granules were seen inside Gram-positive bacteria after chlorpromazine and rose bengal staining. Although the nature of these granules remains unclear, this type of binding may have a role in the inhibition of biochemical processes in the bacterial cells. PMID- 1285647 TI - Dimorphism in Benjaminiella poitrasii: cell wall chemistry of parent and two stable yeast mutants. AB - In the dimorphic zygomycetous fungus Benjaminiella poitrasii, the cell wall compositions of mycelial phase (M), yeast phase (Y) and its yeast form mutants (Y 2 and Y-5) were studied. Chitosan was abundant in M-phase (26.6%) whereas lesser amounts were present in Y-phase (17.3%) and in mutants Y-2 (19.6%) or Y-5 (17.3%). Although chitin was present as a smaller fraction of the total glucosaminoglycan in each of different cell wall preparations, it was almost 3 times more prevalent in M-phase than the Y-phase cells. Cross-linking studies among the various cell wall components in B. poitrasii, suggest linkages among mannans and proteins and glucans and glucosaminoglycans. PMID- 1285649 TI - Effects of some tricyclic psychopharmacons and structurally related compounds on motility of Proteus vulgaris. AB - A simple test for the evaluation of drugs interfering with bacterial motility was established with Proteus vulgaris. With this model, promethazine, 7-hydroxy chlorpromazine, imipramine, 7,8-dioxochlorpromazine and acridine orange were shown to exert significant motility and swarming inhibitory action on Proteus vulgaris strains at subinhibitory concentrations. Quinidine enhanced the antimotility effect of promethazine. The antimotility effect of promethazine was synergized by proton pump inhibitors omeprazole and abscissic acid, but antagonized by extracellular potassium and sodium ions. PMID- 1285650 TI - Pathophysiology of cutaneous inflammation. AB - For the better part of the past century, dermatologists have regarded the skin primarily as a large protective coat. Epidermal keratinocytes were highlighted for their production of keratins and lipids, which contributed to the structural integrity and barrier formation of skin. This "saran-wrap" perspective of skin mentioned keratinocytes only in cutaneous inflammatory reactions as passive targets for damaging diffusion products of infiltrating leukocytes. However, sufficient compelling in vitro and in vivo evidence is rapidly accumulating to support the novel perspective that epidermal keratinocytes can initiate and actively participate in the perpetuation of numerous cutaneous inflammatory reactions that involve a highly diverse array of inciting agents. This presentation emphasizes the keratinocyte and highlights the dynamic immunomodulatory capacity of this overlooked epidermal cell. PMID- 1285652 TI - Peptides and cytokines. AB - In the last decade a number of proteinaceous inflammatory mediators have been structurally characterized. Two of these mediators, tumor necrosis factor alpha (TNF alpha) and Interleukin 1 alpha and beta (IL-1), have pleiotropic properties. Both cytokines are now known to be potent inducers of a number of cell-selective chemotactic cytokines, which belong to a novel superfamily of structurally related low-molecular-weight proteins. One of the most prominent members is termed "IL-8" and represents a neutrophil-selective attractant, whereas another one called "monocyte chemotactic protein 1 (MCP-1)" is a monocyte-selective chemotaxin. Other members seem to be selective chemotaxins for other leukocyte types and subsets. These chemotactic cytokines are produced by a variety of different cells under appropriate stimulation conditions. Large amounts of IL-8 have been detected in scales of psoriatic lesions and may be of importance in explaining predominant neutrophil infiltration in psoriatic lesions. Regulation of gene expression and/or release of these chemotactic cytokines may occur by IL 1 receptor antagonists or soluble TNF-alpha-receptors. So far, natural antagonists to these chemotactic cytokines have not been described; however, pharmacological inhibition of its gene expression and/or release is possible. PMID- 1285651 TI - The role of complement-derived mediators in inflammatory skin diseases. AB - The complement system represents an important nonspecific skin defense mechanism. Its activation leads to the generation of products that not only help to maintain normal host defenses but also mediate inflammation and tissue injury. Proinflammatory products of complement include large fragments of C3 with opsonic and cell-stimulatory activities (C3b and C3bi), low molecular weight anaphylatoxins (C3a, C4a, and C5a), and membrane attack complex. Among them C5a or its degradation product C5a des Arg seems to be the most important mediator because it exerts a potent chemotactic effect on inflammatory cells. Intradermal administration of C5a anaphylatoxin induces skin changes quite similar to those observed in cutaneous hypersensitivity vasculitis that occurs through immune complex-mediated complement activation. Complement activation is involved in the pathogenesis of the inflammatory changes in autoimmune bullous dermatoses. In pemphigus complement activation by pemphigus antibody in the epidermis seems to be responsible for the development of characteristic inflammatory changes termed eosinophilic spongiosis. In bullous pemphigoid (BP) interaction of basement membrane zone antigen and BP antibody leads to complement activation that seems to be related to leukocytes lining the dermoepidermal junction. Resultant anaphylatoxins not only activate the infiltrating leukocytes but also induce mast cell degranulation which facilitates dermoepidermal separation and eosinophil infiltration. Similar complement activation seems to play a more direct role in the dermoepidermal separation noted in epidermolysis bullosa acquisita and herpes gestationis. Anaphylatoxin generation via the alternative pathway activation under light irradiation is implicated in the development of the immediate erythematous phototoxic reactions induced by such well-known chemicals as porphyrin, chlorothiazide, demethylchlortetracycline, and chlorpromazine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285653 TI - Therapy with topical corticosteroids. AB - Therapy with topical corticosteroids has improved greatly in recent years due to both advanced understanding of their mode of action and awareness of their side effects, as well as newly developed derivatives with specifically designed pharmacological properties. Paradoxically, the fear of using corticosteroids has increased on the part of the public during the same period. Treatment of inflammatory or neoplastic skin disorders with topical corticosteroids can be both successful and safe only if certain points are clarified before it is begun. These include (a) specific diagnosis, (b) choice of strength of the compound needed for control of the disease, (c) time schedule for length of therapy and planned patient visits, and (d) choice of vehicle adequate to the skin lesion. Topical corticosteroids of different potency are available today; one can classify these into four groups (weak, medium, strong, very strong) and use them in a patient-tailored treatment. When large areas are to be treated, systemic side effects must be taken into consideration, and compounds that are degraded quickly after absorption are recommended. Finally, the corticophobia of many patients must be addressed by careful information to ensure compliance. Using these guidelines, treatment with corticosteroids is highly effective, easy to use by the patient, and allows a maximum of safety. PMID- 1285655 TI - Future modalities. PMID- 1285654 TI - Steroids versus nonsteroids in the treatment of cutaneous inflammation: therapeutic modalities for office use. AB - Inflammatory skin diseases are often treated successfully with topical substances alone. The basic prerequisites for proper treatment are that the specialist has a good knowledge of the products available, their active substances and bases and their relative properties and actions, as well as precise indications for and effects of long-term use. Treatment should be individualized, and best results are usually achieved with a two-phase schedule, beginning mainly with administration of steroids followed by application of nonsteroid products, such as, in psoriasis, anthralin, coal tar, and calcipotriol. PMID- 1285656 TI - [Asymptomatic ischemia and sudden death]. PMID- 1285657 TI - [The dynamic morphology of the endothelial cells of aortocoronary vessels cultured in vitro]. AB - The morphologic and functional meaning of the endothelial cell, as the first cellular element between blood and tissues, has been investigated since the earliest histological knowledge of the vascular tree. Although there have been multiple attempts for its study, through different biological branches, very little has been comprehended in its dynamic biology, due to technical difficulties and to the apparent simplicity of this extraordinary cellular type. In this research we pretend to establish a morphodynamic pattern of the endothelial cells from the aortocoronary segment, using the particular advantages of tissue culture. Our results, have been obtained through careful observations with light microscopy under different optical systems and the help provided by spaced microcinematography. Our results showed the reality of the images in the different cellular phenomena, particularly, endocytotic pinocytosis, the dynamic of the cellular membrane, and the cell-cell linkages established in vitro. PMID- 1285658 TI - [The primary outcome in transluminal coronary angioplasty: the recent experience of the Instituto Nacional de Cardiologia (1991-1992)]. AB - Percutaneous balloon coronary angioplasty had a slow start in Mexico, and until recently only a relatively small number of procedures have been performed. Since March 1991, the Instituto Nacional de Cardiologia has state-of-the-art fluoroscopic imaging and easy access to a variety of balloon coronary angioplasty catheters and accessories. Under these conditions, an increasing number of PTCAs have been performed (221 procedures in an initial 15 month period). The primary results of PTCA in this patient population is presented as a reference source for results of PTCA in our population. Indication for PTCA was stable angina in 31%, unstable angina in 64% and AMI in 5%. Forty-two percent of the procedures were for multivessel PTCA, with a total of 355 lesions approached (1.6 segments per patient). There were 34% type A, 51% type B and 15% type C lesions. Mean percent stenosis was reduced from 81% to 29% (p < 0.001). There was a 94% success rate in type A lesions, 89% in type B and 77% in type C lesions. Six patients required urgent CABG (2.7%), thirteen had a myocardial infarction (5.9%) and mortality was 1.35% (including one patient with cardiogenic shock who had a noncomplicated failure and had a late in-hospital death). We conclude that with adequate support and equipment, angioplasty results compare favorably to those reported by more experienced groups in developed nations. Also, the necessary number of procedures for the maintenance of competence in PTCA can be done in our country. PMID- 1285660 TI - [The long-term follow-up of 1000 patients with a valve replacement by the prosthesis of the Instituto Nacional de Cardiologia Ignacio Chavez]. AB - The long-term follow-up of patients with bioprosthetic valves manufactured at the Instituto Nacional de Cardiologia Ignacio Chavez is presented. From February 1983 to May 1990, 1068 patients were operated and 1252 valves were replaced. Eighty two percent had rheumatic heart disease with one or more injured valves. In 17% it was a replacement of a failing valve. Seventy three percent of the patients had a low or medium-low socioeconomical status. There were 176 perioperative deaths in the first month after the operation and 150 patients were lost to follow-up. The rest (740) are the subject of this report. Mortality associated with valve related complications had a probability of 0.74 +/- 0.05, it had a significative increase after month 70th, with a 88% survival at that time. The functional class in the whole group improved 90%, with confidence limits for binomial distribution between 85 and 97%. There was also a significant reduction in heart enlargement. There were 161 prosthesis dysfunctions due to valve calcification or rupture, 50 were replaced. Twenty-three patients had hemolysis, and 19 infective endocarditis. There were 6.5% with systemic embolism in spite that only one half of those in which there was an indication, different of the valve replacement, received anticoagulant medication. The use of this prosthesis is on economical and medical satisfactory solution for the problem of a great number of our population of patients. PMID- 1285659 TI - [The usefulness of electrophysiology in a patient undergoing cardiomyoplasty]. AB - The cardiomyoplasty is a new surgical procedure that uses a skeletal muscle electrostimulated in order to reinforce or even substitute partially the cardiac muscle. We present the electrophysiology aspects in a patient with dilated cardiomyopathy that underwent cardiomyoplasty. First the latissimus dorsi muscle was prepared with a neurostimulant ITREL II. During the surgical procedure a dual chamber pacemaker mode DDD brand CPI was placed. After three months, ablation radiofrequency of the AV node was performed in order to control the atrial fibrillation that caused heart failure. By means of the AV block we obtained synchrony between the ventricular stimulation and the latissimus dorsi muscle, and by this the patient improved. Using the modern pacemakers and radiofrequency we can control the bradyarrhythmias as well as the tachyarrhythmias frequent in patients with dilated cardiomyopathy, increasing the success rate of cardiomyoplasty. PMID- 1285662 TI - [Percutaneous valvuloplasty in tricuspid valve stenosis]. AB - This report describes the first successful case of tricuspid valve stenosis by percutaneous double balloon valvuloplasty in Mexico. The gradient decreased from 5 to 0 mmHg, with an increase in valve area by echocardiography and improvement of the jugular vein pulse and disappearance of symptoms. The feasibility of the balloon percutaneous valvuloplasty was demonstrated unequivocally. PMID- 1285661 TI - [The thickness/radius ratio (h/r) of the left ventricle in pure mitral insufficiency]. AB - We studied 11 patients with severe mitral regurgitation (MR). With 2-D echocardiogram we could obtain the septal and posterior wall thickness, left ventricular internal dimensions and ventricular function. With parasternal short axis view we calculate the h/r ratio (left ventricular thickness/radius). The results were compared with normal values: we found important left atrial and ventricle dilatation with significative difference from the normal values (P < 0.001), the diastolic and systolic h/r ratio was significative lower than the normal values (P < 0.005): the systolic wall stress was significative higher in relation to normal values (P < 0.001). We conclude that patients with severe (MR) initially have an important ventricular dilatation but no hypertrophy despite volume overload. The possible explanation is that in early stages of the disease, the afterload of the left ventricle is low and does not trigger the development of hypertrophy. The hypertrophy appears only when the systolic stress is high secondary to myocardial failure. The excessive dilatation of the left ventricle probably damages the myocardial fibers by excessive stretch. This mechanism probably explains the poor late surgical evolution of patients with mitral prosthesis. This we propose that the optimal surgical timing for such patients is when the systolic wall stress elevates over the normal limits, because this is an early sign of myocardial failure. PMID- 1285663 TI - [The prevention of postinfarction left ventricular dilatation by captopril]. AB - Thirty patients admitted to the ICCU with a first myocardial infarction (MI) of any localization, with left ventricular dysfunction revealed by echo-Doppler ejection fraction (EF) < 40%, where randomly divided in three groups of ten: GROUP 1 who was treated with captopril 25 mg orally between the 5th and 7th day post MI, and sustained until the end of the study. GROUP 2 received nifedipine, 10 mg capsules t.i.d. also started between days 5 and 7 post MI. GROUP 3 as a control group was treated conventionally, according to the ICCU routine. The treatment was maintained during 12 months. All patients had a second echo-Doppler at the 5th day post MI to confirm the EF criteria. Also left ventricular end systolic and end-diastolic diameters were measured. At the 5th day post MI and before the drug administration, a low level treadmill stress test was performed in all patients. Subsequently a maximal stress test (Bruce protocol) was done at the first month and at 6 and 12 months of the study. The results showed a significant increase EF in patients of GROUP 1 from an average basal value of 38 +/- 2 to 54 +/- 5 at six months (p < 0.01) and to 60 +/- 3 at 12 months (p < 0.005). The increments observed in patients of GROUP 2 and 3 were more modest; only the 12 month value in GROUP 3, from a basal figure of 41 +/- 3 to 50 +/- 4, had a p < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285665 TI - [Transesophageal atrial stimulation: a technic with the pentapolar catheter electrode]. AB - The objective of the present study was to employ a transesophageal atrial pacing (TAP) technique that would permit the use of the lowest possible currents for consistent atrial capture (CAC) and a more accurate recording system. An electrode catheter containing five poles (E1 to E5) spaced 22 mm apart was constructed, with pole E1 being the most cranial one. The catheter was introduced nasally into the esophagus of eleven adult healthy volunteers, and five unipolar intraesophageal leads were recorded and analyzed until the tracings obtained with E2, E3 and E4 showed P waves of the highest potentials, when the catheter was fixed in place. An electric generator specially constructed for TAP was used. CAC was attempted with each of the 20 stimulating bipoles formed by the permutations of the five poles of the fixed catheter. The least voltage needed for CAC in each individual was always detected in at least one of the six stimulating bipoles formed by the permutations involving poles E2, E3 and E4. Thus, in the population studied as a whole, the minimum voltage range needed to obtain TAP was between 5 and 15 V (mean 11.2 +/- 3.0 V), which was tolerated quite well by the individuals. Pulse durations of more than 10 ms did not lead to use of significantly lower voltages for CAC. Six simultaneous tracings were used during and after TAP, and at least one of them recorded intraesophageal or esophago thoracic bipolar leads. PMID- 1285664 TI - [The incidence of Trypanosoma cruzi antibodies in patients with dilated myocardiopathy at the Instituto Nacional de Cardiologia Ignacio Chavez]. AB - Our objective was to measure the incidence of humoral immune response against Trypanosoma cruzi among patients with a definitive diagnosis of dilated cardiomyopathy at the Instituto Nacional de Cardiologia "I. Chavez" over a year. Thirty seven patients were collected, 15 of them (40%) had antibodies against T. cruzi in two different tests, indirect immunofluorescence and ELISA, the presence of IgG antibody was confirmed through Western blot. There was not differences in clinical picture of cardiomyopathy nor on paraclinical studies. However, there was a significant difference in regard socio economical indexes between the group with positive anti T. cruzi antibodies. They had a predominant rural origin, poor housing and were aware of the vector bug. Also they recalled primary infection in their childhood--American trypanosomiasis could be on important etiologic factor for dilated cardiomyopathy in our country. PMID- 1285666 TI - [Platelet antiaggregants in cardiopathies]. PMID- 1285667 TI - [The detection of viable myocardium with thallium-201]. PMID- 1285668 TI - [The problems of angioplasty in Mexico]. PMID- 1285669 TI - Propranolol-induced hyperreactivity in guinea-pig lung parenchyma strips: possible role of histamine. AB - In vivo and in vitro studies have demonstrated that beta-adrenoceptor blockers enhance the airway smooth muscle contraction to antigen, but the mechanisms are not fully understood. In the present work, we corroborated that propranolol (3.9 x 10(-6) M, 30 min incubation) induces hyperreactivity to antigenic challenge (cumulative concentration-response curve to ovalbumin, 0.01 to 100 micrograms/ml) in lung parenchyma strips from sensitized guinea-pigs. This hyperreactivity was enhanced by indomethacin (3.2 x 10(-5) M) and was unaffected by the lipoxygenase/cyclooxygenase inhibitor phenidone (1 x 10(-4) M). However, the histamine H1 receptor antagonist pyrilamine (1 x 10(-6) M) reduced the potentiation effect of propranolol. These results suggest that bronchoconstrictor prostaglandins, thromboxane A2 and leukotrienes, are not involved in the propranolol-induced lung parenchyma strips hyperreactivity to antigen in vitro, and that histamine may account, at least in part, for such propranolol effect. PMID- 1285671 TI - Spiperone-induced endothelium-dependent relaxation of porcine coronary artery: an investigation into the underlying mechanism. AB - In pig coronary artery rings contracted by the thromboxane analogue U 46619 (9,11 dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F 2 alpha), spiperone induced a relaxation which, at 30 mumol/l, corresponded to a complete reversal of the U 46619-induced contraction. The concentration-response curve for spiperone was bell-shaped. The second phase, i.e. the reduction of the relaxant effect (at concentrations above 30 mumol/l) was due to a contractile effect which was the only response in (1) endothelium-denuded arteries, (2) arteries treated with gossypol or methylene blue, or (3) arteries not precontracted with U 46619. Suramin and reactive blue 2 antagonized the relaxing effect, whereas metitepine, spiroxatrine, propranolol, idazoxan, flupenthixol, atropine and 8 phenyltheophylline did not. The endothelium-independent contraction was not reduced by metitepine. In strips of arteries with intact endothelium, incubated with [3H]adenosine and subsequently superfused with physiological salt solution containing dipyridamole, spiperone evoked an increase in tritium overflow above basal efflux. The present results are compatible with the hypothesis that spiperone releases ATP from the pig coronary artery. ATP, in turn, seems to activate endothelial P2 purinoceptors, leading to the release of endothelium derived relaxing factor (NO) with a subsequent vascular relaxation. PMID- 1285670 TI - Pharmacological profile of a new 5-hydroxytryptamine2 receptor antagonist, DV 7028. AB - The pharmacological profile of DV-7028, a pyrido triazine derivative, showed that it is a potent and selective 5-hydroxytryptamine (5-HT)2 receptor antagonist. DV 7028 bound to 5-HT2 receptors in rat brain membranes with a Ki value of 22 nM and caused shifts to the right of the concentration-contraction curves to 5-HT in rat thoracic aorta and canine femoral arteries, which are attributed to activation of 5-HT2 receptors. The compound was highly active by oral administration (0.1-10 mg/kg) based on blockade of the 5-HT-induced pressor responses in pithed rats. In contrast, DV-7028 had no affinity for 5-HT1A, 5-HT1B and 5-HT1D receptors. The affinity of the compound was 14-26 times greater for the 5-HT2 receptors when compared to 5-HT1C, adrenergic alpha 1, dopamine D2 and histamine H1 receptors. In human platelets, DV-7028 attenuated the aggregation induced by collagen and inhibited the amplifying effect of 5-HT with collagen on platelet aggregation. Furthermore, a 10-day toxicity study revealed that DV-7028 was a safe compound which did not produce lethality at repeated oral doses of 800 mg/kg/day in rats. These results indicate that DV-7028 is a selective and potent 5-HT2 receptor antagonist which is orally active and safe. PMID- 1285673 TI - Effects of buprenorphine on respiratory and cardiovascular functions during hypoxia in anaesthetized rabbits. AB - Respiratory and cardiovascular variables were studied in 10 anaesthetized rabbits, before and after buprenorphine i.v. injections (cumulative doses of 5 to 100 micrograms/kg). In normoxic conditions, buprenorphine induced hypoventilation, due to a decrease in respiratory rate, and bradycardia: mean maximum modifications in ventilation (-17%) and heart rate (-7%) were obtained with buprenorphine 10 and 100 micrograms/kg, respectively. Isocapnic hypoxia, produced by the inhalation of a gas mixture containing 10% O2 in nitrogen for 5 min, provoked a mean 44% increase in base line ventilation and a mean 15% decrease in heart rate. The ventilatory response to hypoxia was not significantly modified by buprenorphine on an average; large decreases in hypoxic drive could still be observed in 3 out of 10 animals with buprenorphine 5 and 10 micrograms/kg. Buprenorphine enhanced hypoxia-induced bradycardia: a mean maximum decrease in heart rate (-29%) was reached with 10 micrograms/kg of this opioid. PMID- 1285672 TI - Effects of nilvadipine on regional cerebral blood flow and skin blood flow in anesthetized cats. AB - The effects of an intravenous injection of the novel calcium channel blocker, nilvadipine, on the relative regional cerebral blood flow and relative regional skin blood flow were studied in anesthetized cats using the laser-Doppler method. The effects of nilvadipine were compared with those of nicardipine hydrochloride (nicardipine). Nilvadipine and nicardipine both increased the relative regional cerebral blood flow dose-dependently, in spite of their hypotensive effect. At a dose of 32 micrograms/kg, nilvadipine and nicardipine increased the relative regional cerebral blood flow by 61 +/- 8% and 25 +/- 10% of the predrug value, respectively, 15 min after administration. At this time, both drugs induced a comparable degree of hypotension: -18 +/- 3% of the predrug value for nilvadipine and -25 +/- 2% for nicardipine. After nilvadipine, the relative regional cerebral blood flow enhanced by 45 +/- 10% 180 min after drug administration, whereas after nicardipine, it returned to the predrug value within 60 min. In contrast, the increase in relative regional skin blood flow produced by nilvadipine (32 micrograms/kg) and nicardipine (32 micrograms/kg) was 23 +/- 15% and 32 +/- 8% of the predrug value, respectively, 5 min after drug administration. The effect of nicardipine on the relative regional skin blood flow, compared with that of control, was significantly higher. These results indicate that nilvadipine exhibits a pronounced and longer-lasting effect on the relative regional cerebral blood flow, compared with the relative regional skin blood flow, and that its action on the relative regional cerebral blood flow is more potent than that of nicardipine. PMID- 1285674 TI - Cardiotoxic effects of high doses of cyclophosphamide in albino rats. AB - A histopathological study of cyclophosphamide-induced cardiotoxicity has been conducted in 43 Swiss albino rats. Multiple interstitial myocardial haemorrhage, multifocal myofibre necrosis, inflammatory reaction, vascular changes, pericarditis and valvulitis, mainly in the heart ventricles, have been observed. Previous results have suggested that cyclophosphamide directly damages the vascular endothelium, followed by the extravasation of blood containing high levels of the drug, and resulting into a toxic damage of the muscle cells. Our results are in favor of this hypothesis. PMID- 1285675 TI - Nicotinic receptors in healthy and ischemic heart with special reference to the Bezold-Jarisch reflex. PMID- 1285676 TI - Studies on mercury-induced myotonia in the mouse diaphragm. AB - Muscle contracture and myotonia of mouse diaphragm, induced by HgCl2, were studied. HgCl2 induced myotonia of mouse diaphragm only on condition that the Hg2+ contracture was inhibited by 0.005-0.01 mM NaCN. A higher concentration of 0.05 mM NaCN abolished both the Hg2+ contracture and Hg2+ myotonia. This finding suggests that the Hg2+ contracture masked the Hg2+ myotonia which was less sensitive to the inhibitory action of NaCN. This differential inhibitory action of NaCN on Hg2+ contracture from Hg2+ myotonia implies a possibility that NaCN antagonized the actions of HgCl2 not only through a simple chemical interaction. Hg2+ myotonia was characterized by an increase in contractile amplitude and a prolongation of contractile duration which were associated with stimulus-bound repetitive action potentials and an increase in membrane input resistance. A low Cl- medium as well as a Cl- channel blocker (9-anthracene carboxylic acid) not only by themselves induced myotonia, but also antagonized Hg2+ myotonia. Thus, Hg2+ appeared to mimic the Cl- channel blocker in inducing myotonia through a blockade of the Cl- channel. K+ channel blockers (4-aminopyridine, uranyl nitrate and tetraethylammonium chloride), as well as low (0.25 mM) Ca2+ Krebs, augmented Hg2+ myotonia while ATP-sensitive K+ channel blockers (tolbutamide and glibenclamide) antagonized Hg2+ myotonia (in the presence of NaCN). Since glibenclamide did not affect myotonia induced by a Cl- channel blocker, it was suggested that glibenclamide inhibited the Hg2+ myotonia through an interaction either directly or indirectly with NaCN on the sarcolemma. All of these findings suggest that K+ channels (delayed rectifier and Ca(2+)-activated K+ channel) functionally cooperated with the Cl- channel of the sarcolemma in the regulation of the skeletal muscle contraction. In this study, K+ channel blockers synergistically cooperated with Cl- channel blockers in inducing myotonia of the mouse diaphragm, while an ATP-sensitive K+ channel blocker exerted only an opposite effect on NaCN. Ca2+ appeared to play an important role in regulating the ionic channel activities, especially the Cl- channel, since low Ca2+ markedly potentiated not only Hg2+ but also low Cl- in inducing myotonia. PMID- 1285677 TI - Serous cutaneous glands of the western spade-foot toad Pelobates cultripes (Amphibia, Anura): an ultrastructural study on adults and juveniles. AB - The venom glands of the western spade-foot toad Pelobates cultripes were studied under light and electron microscopes. The glands exhibit the structural patterns usual in anurans, including the typical secretory syncytium. The peripheral cytoplasm contains a single row of nuclei and secretory organelles related to proteosynthesis. The inner cytoplasm is filled with large vesicles holding a thin product which originates from the merging of smaller ones containing a thicker material derived from the Golgi apparatus. The appearance and maturation of P. cultripes venom have been compared with patterns of biosynthesis and secretory evolution described in serous cutaneous glands of several anuran species. Following these criteria, the traditional trends in the terminology and classification of serous glands in anuran skin are discussed and reviewed. PMID- 1285679 TI - The development of the caeca in the chick embryo. Morphometric and morphological remarks. AB - Quantitative aspects of the organogenesis of the chick embryo caecum (proximal and distal tracts) were investigated from the 8th to the 15th day of incubation. Histological sections were studied by means of a computerized morphometric system and a semiautomatic digital system (Videoplan 2). The total area of sections, of the lumen, the caecal wall and its components (subserous stratum, muscle layer, lamina propria, epithelium) and the thickness of the epithelium and muscle layer were measured. The mean +/- S.E.M. of the obtained values was calculated. The percentage of shrinkage, due to histological procedures, was calculated for each day considered. The mean values for each day of incubation were modified on the basis of the shrinkage percentage. The differences between the mean values of the areas of the proximal and distal tract were statistically evaluated. Exponential curves and the r coefficient were determined in order to evaluate the general growing pattern of the mean area of the caecal wall components as a function of age. The obtained results demonstrate that there are some differences between the proximal and distal tract of the caecal anlage in the growth pattern of the wall components. In the proximal caecal tract, the lamina propria showed the highest growth rate, while in the distal tract, the caecal wall component the subserous stratum did. Moreover, the caecal anlage showed different developmental behaviour from the ileum, duodenum and colon in the same chick embryo. PMID- 1285678 TI - Morphological observations on the glands of the oesophagus and stomach of adult Rana esculenta and Bombina variegata. AB - Examination of serial sections of the oesophagus and stomach of Rana esculenta and Bombina variegata revealed that oesophageal peptic glands were only present in Rana, where gastric glandular cells performed only one functional role, represented by HCl production. In contrast, in Bombina the gastric glands were mainly of oxynticopeptic cells with dual oxyntic and peptic roles, reflected morphologically by distinct different areas of their cytoplasm. During activity of the oxynticopeptic cells cytoplasmic differences were reduced because the tubular profiles, carrying HCl, and zymogen granules emerged at the cell apex. PMID- 1285680 TI - Comparative anatomical and ultrastructural features of the sensory papillae in the tongue of hibernating bats. AB - The papillae of the tongue dorsal surface of the insectivorous, hibernating bats (Vespertilionidae and Rhinolophidae), whose function is mainly sensorial, consist of two circumvallate papillae, two foliate papillae, located at the side edges at the glossopalatine arch, and numerous fungiform papillae. The circumvallate and foliate papillae are characterized not only by their position, but also by presence of several taste buds which open through the external orifice of the gustatory canal into the cavity of the vallum, or furrow, which divides the two folds of the lingual mucosa. The fungiform papillae (extremely numerous on the whole dorsal surface) are characterized by an unusual arrangement (along 3 oblique lines on the anterior two-thirds and predominantly on the middle line of the tongue body) and by the presence of only one to three taste buds which open on the heavily keratinized dorsal epithelial surface. The taste buds are made up of sensory cells with a light or dark matrix; their apical cytoplasmic expansions are not found beyond the middle part of the gustatory canal, in contrast with the circumvallate and foliate papillae which protrude from the orifice of the gustatory pore. Comparisons with the papillae of other types of bats and Insectivora and evaluations of the morphological characteristics and their functional values (unusual areas of distribution of the papillae, apical cytoplasmic expansions and behaviour of microfolds observed under SEM) have been made in different environmental conditions and nutritional habits, with attention to the mechanical events in the course of feeding. PMID- 1285682 TI - History of the anatomy of the funiculus umbilicalis in mammals. AB - The authors, based on a bibliographic search, present a brief survey of the history of the anatomical aspects of the funiculus in mammals, including the evolution of their interpretation and their relationship with the evolution of scientific and technological approaches to their study. PMID- 1285681 TI - The innervation of the lingual papillae of the buffalo. A histochemical and immunohistochemical study. AB - The neural structures of the lingual papillae of the buffalo tongue were studied by means of neurohistological and immunohistochemical techniques and by the Ruffini gold chloride impregnation method. The circumvallate papillae were found to be richly innervated; the conical and filiform papillae were poorly innervated; and the innervation of the fungiform and lenticular papillae was intermediate. The following neural structures were identified: myelinated and non myelinated fibers, free nerve endings and encapsulated end organs, lamellated corpuscles, Ruffini-like endings, and ganglia containing few cell bodies. Brain derived neurofilament and the S-100 proteins were found in the majority of these structures. These findings indicate that the innervation of the lingual papillae of the buffalo is fairly well developed. It appears to be similar to that of cattle. PMID- 1285683 TI - The microvasculature of the lingual mucosa in Capra hircus. AB - The microvasculature of the lingual mucosa of the goat was studied by SEM using microvascular corrosion casts. A complex microcirculatory system was observed to supply the large number of papillae, which had a wide structural variety. Generally, the organization of the vascular network in the lingual papillae was found to be influenced by the nature of the microcirculation in the lamina propria. Another characteristic feature noted was the presence of numerous valves in the venules situated in the lamina propria. They were oriented toward the broader side of the venules and probably control the rapid outflow of blood. This in turn most probably leads to an increased mucosal blood supply, which might sustain both mechanical and gustatory functions. PMID- 1285684 TI - Microscopical aspects of root resorption of human deciduous teeth. AB - In order to obtain detailed information on the tissue changes which occur during physiological root resorption, 52 human deciduous teeth at various stages of resorption were studied under light microscopy. The early stage of root resorption was defined as resorption of not more than one third of the root length; the late stage was defined as resorption of more than one third. A close topographical interrelationship was found among che sites of pressure of the permanent tooth, the extent of root resorption and the types of tissue changes. Linear resorption (which reflects suspension or marked slowing down of resorption) and redeposition of hard tissue were more pronounced at the early stage of resorption, while lacunar resorption was more pronounced at the late stage. There were pronounced haemorrhagic and inflammatory infiltrates within the pulp at the late stage of resorption and the subodontoblastic cells disappeared as the infiltrates took over the tooth. False denticles were found frequently, especially at the early stage of resorption. Unexpectedly, acellular cementum was found to be deposited against secondary dentine at the cuspidal tip of the pulp chamber of seven teeth, independently of any sign of resorption nearby. These data indicate that: 1) the pressure exerted by a permanent tooth is the most important factor in the differentiation of odontoclasts. 2) the extent of lacunar (i.e., active) resorption correlates directly with the resorption rate, which is higher at the late stage of root resorption. 3) inflammation is a consequence, rather than a cause, of resorption; it may lead to the loss of subodontoblastic cells and a consequent decrease in the ability of the pulp cells to replace damaged odontoblasts. 4) the pulp of the deciduous tooth might be cementogenic in some way, given that about 13% of the samples were found to be so. PMID- 1285685 TI - On the presence and ultrastructure of valves in the lymphatic vessels of the canine ovary. AB - The origin and course of the intraovarian lymphatic vessels were examined by means of histologic studies of the gonads of pubertal female dogs. The small vessels that were present in the cortex near the follicles and corpora lutea flowed into an anastomotic network located at the margins of the medulla. Vessels of larger caliber were found to originate from the medulla and to reach the hilum by an approximately rectilinear pathway. In concordance with their previous findings in other species, the authors identified numerous semilunar valves in the lymphatic vessels of the cortex. Their ultrastructure is described. PMID- 1285686 TI - [Meta-analysis of therapeutic trials of primary prevention in ischemic cardiopathies by hypocholesteremic treatment]. AB - The prevention of lipid-related coronary risk by lipid lowering drugs or diet has been the object of several therapeutic trials. This meta-analysis comprises the 6 available primary prevention trials (representing 30,695 subjects). There was an overall reduction of non-lethal infarcts (-26%) and coronary events (-18%) in the treatment groups. There was a tendency to less coronary deaths (-10%), though not statistically significant, and no difference in mortality due to all causes was observed. Some questions remain unanswered about the fact that the reduced incidence of ischaemic heart disease did not affect global mortality. This fact could be explained by an inadequate duration of treatment or follow-up, to an effect limited to chronic infarction or to eventual unidentified adverse effects (the meta-analysis does not show any significant differences in mortality due to cancer or accidental death). PMID- 1285688 TI - [The "duration of administration" factor in studies of clinical pharmacology of hypolipemic drugs]. AB - Clinical pharmacological trials of lipid lowering drugs should first of all indicate the duration of interruption of previously used lipid lowering drugs. The duration of interruption should be at least 4 weeks for inhibitors of HMG CoA reductase, 6 weeks for a second generation fibrate or a resin and over 6 months for probucol. In order to obtain the maximum therapeutic effect, a 4 week treatment period is sufficient for a HMG CoA reductase inhibitor or a resin. On the other hand, this period is longer for a fibrate and a 6 week treatment period is to be preferred with this family of drugs. The efficacy of probucol on the lipid fractions can only be assessed after several months' therapy. In future, a more accurate classification of patients with respect to their physiopathology should provide a better evaluation of the comparative efficacy of the different lipid lowering drugs. PMID- 1285687 TI - [Mechanism of action of antilipemic drugs]. AB - The study of the modes of action of lipid lowering drugs is important in order to evaluate their effects on the different lipid fractions and their possible secondary effects. These studies include: direct and indirect measurements of cholesterol absorption, the measurement of the principal enzymatic activities implicated in lipoprotein metabolism, especially those of lipases which play a fundamental role in the metabolism of particles rich in triglycerides and the inverse transport of cholesterol, and, finally, the measurement of intracellular enzyme activities. These last analyses are generally much more complex. Despite recent advances in all these investigative techniques, the mechanisms of action of many lipid lowering drugs remain obscure. Many have indirect modes of action like the inhibition of hydroxymethyl-glutaryl CoA by the fibrates and the mechanisms of action of the most recently introduced drugs are more complex than usually described. All these factors are important because the development of atherosclerosis depends on qualitative variations of the lipoproteins. PMID- 1285689 TI - [Methodology of phase II clinical trials of hypocholesteremic drugs: which criteria?]. AB - Phase II is crucial in drug trials: during this period the first patients are exposed to the drug and the results influence the continuation of the development and the success of later trials. This stage is fundamental in lipid lowering drugs considering the costs of development and potential benefits for public health. The choice of pertinent criteria for the design of a lipid lowering drug trial depends on the analysis of data acquired during previous large scale trials. These criteria should demonstrate the potential of the tested drug and the best conditions of its administration. It is especially at this stage that the drug dosage optimising the efficacy/tolerance ratio should be determined. Analysis of large scale prevention trials indicates LDL-cholesterol as the principal criterion. It is related to coronary risk in the major trials of lipid lowering drugs. A reduction of LDL-cholesterol gives a good numerical estimate of the expected reduction of cardiovascular risk. It is then possible to formulate the hypotheses required for the design of these trials, in particular to calculate the size of the treatment group required. The total cholesterol should also be measured above all because of the large amount of data correlating it with cardiovascular risk. The HDL-cholesterol and triglycerides should also be taken into account even though some of the data concerning these parameters is controversial. The discrimination obtained by measuring HDL-cholesterol is without any doubt crude, and future criteria should enable more accurate and rapid evaluation of lipid lowering activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285690 TI - [Methodology of phase III clinical trials of hypocholesteremic agents. Do any reliable substitution criteria exist?]. AB - Pathological events such as myocardial infarction or cardiac death due to hypercholesterolaemia are easily quantified and reliable parameters for assessing the value of lowering the serum cholesterol. However, these events are relatively rare during Phase III clinical trials, the duration of which does not exceed 1 year. To solve this problem, intermediary or substitute criteria have to be used which are predictive of cardiovascular complications related to this pathology. Substitute criteria such as total cholesterol LDL-cholesterol and HDL-cholesterol have been validated by epidemiological and/or clinical studies which have established their predictive value. These primary and secondary prevention trials and regression studies have been analysed. The possibility of more sensitive predictive values of certain lipid fractions and particles is discussed. PMID- 1285691 TI - [Primary prevention trial. Methodological problems]. AB - Primary prevention trials are the best method of demonstrating the true value of medical intervention to correct abnormalities of lipid metabolism. A large number of patients must be followed up for a long period and this explains the complexity of the logistic problems which are encountered. However, these trials must conform to the classical guide lines of all clinical trials: an accurate definition of the study population, a principal criterion of adjustment which satisfies the golden rule "One question, one study". PMID- 1285693 TI - [Mediterranean nutrition: a model for the world?]. AB - The protection of Mediterranean populations against ischaemic heart disease has been recognised ever since the "Seven Countries" Study by Keys. It is probably related to the life style and, in particular, to the dietary habits of these populations. The Mediterranean diet is characterised by a certain frugality, a low intake of saturated animal fats contrasting with a high but reasonable intake of mono or polyunsaturated fatty acids, slow carbohydrates, fresh vegetables rich in antioxidating vitamins, fish and wine. These dietary habits have been shown to improve the lipid profile (not only lowering LDL-cholesterol but also raising the HDL-cholesterol), platelet activity and to reduce the phenomena of lipoperoxidation. The roles played by garlic and onions are controversial. Nevertheless, at pharmacological dosages, they have cholesterol lowering, fibrinolytic and antiaggregant effects. These dietary habits, which have been proved to be beneficial, should therefore be preserved in our country. PMID- 1285692 TI - [Evaluation of acquired data on long-term risk of hypolipidemic treatments]. AB - At present, it is very difficult, if not impossible, to draw reliable conclusions about the long-term risks of lipid lowering therapy. Many so-called "long-term" trials only cover a few years of treatment, comparative studies versus placebo are very rare and the notification of acute events in the context of pharmacovigilance does not provide information about the long-term risk. However, analysis of large scale primary or secondary prevention trials, the Lipid Research Clinics study with cholestyramine, the Helsinki cardiological study with gemfibrozil, the Coronary Drug Project with clofibrate and nicotinic acid, has not shown any significant differences between the treatment and control groups, in particular with regards to the prevalence of malignant disease. These reassuring observations contradict those of the WHO study with clofibrate: a significant increase in the incidence of cancer, especially gastrointestinal, is observed in the treatment group. Therefore, despite the absence of confirmed long term clinical or biological adverse effects of lipid lowering drugs (apart from the WHO clofibrate study), the physician must remain vigilant, especially as the long-term risks are difficult to assess. PMID- 1285694 TI - [Methodological problems of prevention/regression trials of atherosclerosis]. AB - Animal models of atherosclerosis have improved our understanding of the pathogenic mechanisms involved in the formation of the atherosclerotic plaque. However, extrapolation of these data to the clinical situation is difficult. In addition, evaluation of the prevention or regression of atherosclerosis raises methodological problems. Although improved techniques provide a better evaluation of the extension of the plaques and their functional consequences, a number of points remain undecided: when to intervene, in which patients and how to extrapolate the results. A standardisation of the methods of evaluation of the atherosclerotic plaque is essential as is the fact that the benefit observed should be a reduction in cardiovascular complications and not simply the progression or regression of an angiographic lesion. PMID- 1285695 TI - [Technique for measuring the atheroma volume in men]. AB - The evaluation of the impact of therapy on the evolution of atherosclerotic lesions or restenosis after angioplasty requires the use of techniques of vascular imaging. The reference invasive method is digital angiography although it does not provide data on the arterial wall thickness. This parameter can be approached however by intravascular ultrasound imaging, a technique which has a number of important practical limitations. Of the non-invasive techniques available, Doppler ultrasonography is the only one that can be used in clinical trials. Nuclear magnetic resonance imaging is the object of much research and is without doubt the technique of the future. The choice of model of atherosclerosis influences that of the imaging technique: cineangiography for coronary arteries, digital angiography or Doppler ultra sonography for lower limb arteries and Doppler ultrasonography for the carotid arteries. Interpretation of angiography is now performed quantitatively by videodensitometry. Interpretation of other techniques should be performed by a second independent observer and "blinded" with respect to the order in which the investigations were performed and to the treatment administered. The criteria of judgment may be qualitative (progression, stabilisation, regression) or quantitative, the latter having a number of advantages over the former. Of the quantitative criteria, the percentage stenosis, though widely used, does not fully answer the question posed, and neither does the diameter of the stenosis. The volume of the arterial lumen calculated from videodensitometric data would seem to be the best, by its sensitivity and additivity, current angiographic parameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285696 TI - [Hypolipidemic treatment after myocardial infarction]. AB - Treatment of hyperlipidaemia is even more important after than before myocardial infarction. Currently available data should be confirmed by larger studies including women and lasting over 10 years. Analysis of the results would be facilitated by studying comparable groups with respect to left ventricular function and severity of the coronary disease. The total serum cholesterol should optimally be under 2 g/l and the LDL-cholesterol under 1.30 g/l. However, coronary artery disease is a multifactorial condition and the correction of only one predisposing factor, albeit a major one, is not sufficient for effective prevention. PMID- 1285697 TI - [Evaluation of anti-atheromatous properties of calcium channel inhibitors]. AB - Calcium is involved in several biochemical atherogenesis processes and its activity is antagonised in cell and animal experimental models by all classes of slow channel calcium inhibitors. However, the doses required in animals to slow the development of atherosclerotic lesions are above therapeutically acceptable doses in man. The clinical relevance of their anti-atherosclerotic activity in the few clinical studies undertaken is difficult to assess because of the variable criteria of judgment used. PMID- 1285698 TI - [Inhibitors of angiotensin-converting enzyme and processus of intima proliferation in atherosclerosis]. AB - The renin angiotensin system is a negative feed-back system of blood pressure control. A number of concordant experimental and clinical results indicate that the angiotensin family has a trophic effect on the vessel wall. These properties of the angiotensins favorise the proliferation of the cells which make up the vessel wall and also amplify the vascular dysfunction in the absence of the inhibitory regulations. Angiotensin converting enzyme inhibitors could be a valuable therapeutic method of counteracting these deleterious effects on the composition and function of the vessel wall. PMID- 1285699 TI - [Atheroma and antithrombotic agents]. AB - The clotting factors are thought to play a part in the development of atherothrombosis, not only in the formation of occlusive thrombosis but also in the progression of vessel wall lesions. Activated platelets participate in thrombus formation and stimulate the proliferation of smooth muscle cells via the growth factor that they liberate. Many therapeutic trials have been carried out with different platelet-inhibiting drugs and some have show a preventive effect on occlusive events. The role of platelet anti-aggregants in the prevention of vessel wall lesions is more difficult to demonstrate. Activation of the coagulation system or a defect in the fibrinolytic system result in the accumulation of intravascular and intraparietal fibrin. The increases in plasma concentration of factors such as the fibrinogen, factor VII, a fibrinolytic inhibitor, PAI-1, are considered to be markers of coronary risk. The preventive effect of low-dose vitamin K antagonists which reduce factor VII activity and the effect of metformin which counteracts insulin resistance and reduces PAI-1 concentrations, are at present under trial. Some platelet antiaggregants and lipid lowering drugs reduce fibrinogen, factor VII and PAI-1 concentrations. Results of therapeutic trials of these molecules are eagerly awaited. PMID- 1285700 TI - [Atheroma and fish oils]. AB - The reduction in cardiovascular mortality and morbidity observed over the last decade may be considered to be largely the result of the prevention of lipid disorders. The beneficial effects of diet and increased consumption of unsaturated fatty acids on ischaemic heart disease is a generally accepted concept. The low death rate from coronary artery disease amongst Greenland eskimos who eat a lot of fish has been confirmed by epidemiological studies of other large fish eating populations like the Japanese. The results reported by Bang and Dyerberg have been confirmed by the Zutphen study undertaken by Kromhout in the Netherlands. Fish oil act by the intermediary of the omega-3 fatty acids. Fish oil is rich in high unsaturated omega-3 fatty acids, the most important one being eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). On the basis of epidemiological studies and clinical and experimental observations, it would appear that the consumption of marine polyunsaturated fatty acids has at least a preventive effect on phenomena of atherosclerosis and thrombosis. Their efficacy on the regression or stabilisation of the atheromatous plaque has not been demonstrated. The sites of action are multiple: decreased platelet aggregation; inhibition of thromboxane A2 production; reduction of triglyceride and VLDL concentration; improved blood rheology; action on the endothelium and proliferation of the intimal cells, vascular tone and vasomotricity. The importance of cardiovascular mortality and the hopes raised by clinical and epidemiological trials justify the pursuit of complementary studies on the efficacy and modes of action of marine polyunsaturated omega-3 fatty acids. PMID- 1285701 TI - [Vascular action of prostaglandins: atheroma, vasoconstriction and ischemia]. AB - Prostaglandins seem to be involved in all stages of the atheromatous process, especially coronary artery disease. This condition is associated with decreased prostacyclin synthesis. Prostacyclin, by the intermediary of cAMP, regulates cholesterol metabolism in the smooth muscle cell by mobilising intracellular cholesterol. Thromboxane is liberated in great quantities in acute coronary syndromes such as myocardial infarction (especially when fibrinolysis is performed) and unstable angina. It is also found in high concentrations in coronary sinus blood during stress tests inducing transient ischaemia in patients with stable angina. There is a relationship between the degree of ischaemia and plasma concentrations of thromboxane whereas prostacyclin levels remain unchanged, causing an imbalance between these two substances during ischaemia. Thromboxane is also responsible for the acute pulmonary vasoconstriction induced by the neutralisation of heparin by protamine. The introduction of molecules modifying the synthesis of these prostaglandins or inhibiting their effects by specifically blocking their receptors should open up new therapeutic possibilities. PMID- 1285702 TI - [Evaluation of trials on regression of atheromatous lesions with hypolipemic drugs]. AB - Experimental studies have demonstrated regression of atheromatous lesions with diet and lipid lowering drugs. In order to confirm these results clinically, reliable angiographic methods of analysis must be developed along two lines: quantitative by consensus between independent "blinded" experts, qualitative by digitalizing radiological images. Given the reproducibility of these methods, a variation of 17 to 20% in the size of the atheromatous plaques should be required to affirm a change. Five studies have been performed in patients with atherosclerosis associated with variable degrees of hyperlipidaemia and compared with a control group. NHLBI type II: 59 out of 146 patients with type II hyperlipoproteinaemia were treated with cholestyramine for 5 years with reduction of the progression of > 50% stenosis but no evidence of regression (6%). CLAS: 80 out of 160 coronary patients were treated with cholestipol and nicotinic acid for 2 years and a reduction of progression and a regression of lesions were observed in 16% of cases. Nikkila: 28 coronary patients with hyperlipidaemia were given clofibrate or nicotinic acid for a 7 year period, stabilising the evolution but with no signs of regression. FATS: 74 of 120 coronary patients with apolipoprotein B concentrations of over 1.25 g/l were given lovastatine cholestipol or nicotinic acid-cholestipol for 2.5 years: regression of coronary lesions was observed in 32 to 39% of cases depending on the treatment administered. Olsson: reported the same results for femoral atheroma with treatments associating fenofibrate and nicotinic acid: 20% regression and reduction of progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285704 TI - Dosimetry Workshop: extremely-low-frequency electric and magnetic fields. AB - A workshop on the dosimetry of extremely-low-frequency fields was held to assess current knowledge in this field and to develop a set of recommendations for new research that meets the needs of health risk assessment, in particular, the assessment of cancer risk. The workshop was sponsored by the Electric Power Research Institute and was held on March 20-22, 1991, in Carmel, California. Major topics of the workshop were microdosimetry of induced electric fields, scaling of induced fields among biological systems from cells to humans, and the problem of defining a biologically effective "dose." A number of research recommendations were developed, the most important of which are to (1) characterize the natural background electric and magnetic fields in tissues and near cells, (2) improve experimental exposure geometries to allow accurate characterization of induced fields in samples, (3) design experiments to distinguish between electric and magnetic field mechanisms, (4) develop standard in vitro biological systems with reproducible and well-established responses to fields, and (5) develop definition of dose with respect to fields at the primary site of interaction. PMID- 1285703 TI - [Trials of primary prevention by diet or hypolipidemic treatment]. AB - The experimental demonstration of a causal relationship between serum cholesterol and coronary artery disease has been confirmed by primary prevention trials. Four trials have fulfilled the methodological criteria of this type of research. Three of them have involved lipid lowering drugs (clofibrate, cholestyramine and gemfibrozil) and the fourth a diet low in saturated fats. They were undertaken in middle aged hypercholesterolemic men and offered 9 out of 10 chances of demonstrating a significant reduction in the prevalence in ischaemic heart disease if it existed. The serum cholesterol of the treatment groups was on average 8 to 13% lower to that of the control groups. In the 4 trials, the prevalence of severe coronary events, infarction and sudden death, was significantly reduced (relative reduction of 19 to 47%). The reduction in individual risk was proportional to the reduction in serum cholesterol. In 2 trials, this reduction was related to variations in the opposite directions of the LDL and HDL cholesterol: a reduction of 1% in LDL-cholesterol reduced the risk by 2% and an increase of 1% of HDL-cholesterol reduced it by 2 to 4%. None of the trials were designed to evaluate the effect of intervention on mortality. In one of them (clofibrate), all cases of mortality were temporarily increased during the trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285706 TI - Macroscopic dosimetry of power-frequency electric and magnetic fields. PMID- 1285705 TI - Magnetite in human tissues: a mechanism for the biological effects of weak ELF magnetic fields. AB - Due to the apparent lack of a biophysical mechanism, the question of whether weak, low-frequency magnetic fields are able to influence living organisms has long been one of the most controversial subjects in any field of science. However, two developments during the past decade have changed this perception dramatically, the first being the discovery that many organisms, including humans, biochemically precipitate the ferrimagnetic mineral magnetite (Fe3O4). In the magnetotactic bacteria, the geomagnetic response is based on either biogenic magnetite or greigite (Fe3S4), and reasonably good evidence exists that this is also the case in higher animals such as the honey bee. Second, the development of simple behavioral conditioning experiments for training honey bees to discriminate magnetic fields demonstrates conclusively that at least one terrestrial animal is capable of detecting earth-strength magnetic fields through a sensory process. In turn, the existence of this ability implies the presence of specialized receptors which interact at the cellular level with weak magnetic fields in a fashion exceeding thermal noise. A simple calculation shows that magnetosomes moving in response to earth-strength ELF fields are capable of opening trans-membrane ion channels, in a fashion similar to those predicted by ionic resonance models. Hence, the presence of trace levels of biogenic magnetite in virtually all human tissues examined suggests that similar biophysical processes may explain a variety of weak field ELF bioeffects. PMID- 1285707 TI - Electromagnetic field dosimetry: issues relating to background, noise, and interaction mechanisms. PMID- 1285708 TI - Estimates for ELF effects: noise-based thresholds and the number of experimental conditions required for empirical searches. AB - Interactions between physical fields and biological systems present difficult conceptual problems. Complete biological systems, even isolated cells, are exceedingly complex. This argues against the pursuit of theoretical models, with the possible consequence that only experimental studies should be considered. In contrast, electromagnetic fields are well understood. Further, some subsystems of cells (viz. cell membranes) can be reasonably represented by physical models. This argues for the pursuit of theoretical models which quantitatively describe interactions of electromagnetic fields with that subsystem. Here we consider the hypothesis that electric fields, not magnetic fields, are the source of interactions, From this it follows that the cell membrane is a relevant subsystem, as the membrane is much more resistive than the intra- or extracellular regions. A general class of interactions is considered: electroconformational changes associated with the membrane. Expected results of such as approach include the dependence of the interaction on key parameters (e.g., cell size, field magnitude, frequency, and exposure time), constraints on threshold exposure conditions, and insight into how experiments might be designed. Further, because it is well established that strong and moderate electric fields interact significantly with cells, estimates of the extrapolated interaction for weaker fields can be sought. By employing signal-to-noise (S/N) ratio criteria, theoretical models can also be used to estimate threshold magnitudes. These estimates are particularly relevant to in vitro conditions, for which most biologically generated background fields are absent. Finally, we argue that if theoretical model predictions are unavailable to guide the selection of experimental conditions, an overwhelmingly large number of different conditions will be needed to find, establish, and characterize bioelectromagnetic effects in an empirical search. This is contrasted with well-established chemical dosimetry, which is much simpler. Because of the large number of possible electromagnetic field conditions, we also conclude that in vitro studies, rather than in vivo studies, should be emphasized in studies aimed at discovering and characterizing mechanisms for bioelectromagnetic effects. PMID- 1285709 TI - Bioelectric background fields and their implications for ELF dosimetry. AB - Electrically active cells, such as those comprising nerve, muscle, or bone, produce ELF currents not only across themselves but also in the surrounding tissue including the tight extracellular spaces between cells. An analysis based on "cable models" of neurons or muscle cells is herein used to estimate those extracellular (or "pericellular") current densities. In order to explore frequency bands the neural or muscle action potentials are represented by a Fourier series of sine wave components. The results of this analysis suggest that endogenous currents in, or near, nerve and muscle are far stronger (higher density) than currents likely induced by exogenous ELF fields--such as 1 microT, 60 Hz magnetic fields. This holds true even for "higher harmonics" including those at or near 60 Hz. PMID- 1285710 TI - Endogenous ionic currents and DC electric fields in multicellular animal tissues. AB - Through the use of the non-invasive vibrating probe technique for detecting extracellular ionic currents developed in 1974 [Jaffe and Nuccitelli: J Cell Biol 63:614-628, 1974], embryonic currents have been detected in a wide range of animal systems (recently reviewed in [Nuccitelli, Noninvasive Techniques in Cell Biology. New York: Wiley-Liss, 1990, pp 273-310]. In four of these studies, the corresponding electric field has been measured within the animal tissue. Such measurements of internal electric fields are quite challenging because they involve the insertion of microelectrodes into the developing tissue along specific regions of current flow. This paper reviews the evidence for endogenous transembryonic currents and dc electric fields in animal systems and provides the range of values for such physiological fields. These data should provide a guide to the range of imposed electric field strengths that could influence normal biological functions in living organisms. PMID- 1285711 TI - Experimental macroscopic dosimetry for extremely-low-frequency electric and magnetic fields. AB - Environmental and laboratory exposure to electric and magnetic fields (EMF) in the extremely-low-frequency range (ELF) produces electrical quantities that interact directly with the exposed biological system on a scale small compared to the size of the human body but large with respect to cellular dimensions. The purpose of this paper is to describe these macroscopic electrical quantities and their characterization through measurements on living systems and experimental models. Electric field exposure results in a total induced current, surface electric fields, internal electric fields, and internal currents. Magnetic field exposure results in internal magnetic field, internal electric fields, and internal currents. Basic properties of fields and matter determine the methods by which these quantities can be measured. Quantification or dosimetry for these parameters on a macroscopic basis can be directed to the whole body, a cross section across the body, a local surface area, or a local volume. Models of varying degrees of sophistication have been used to establish spatial distributions of external fields and internal fields and currents. PMID- 1285712 TI - Methodological approaches to EMF microdosimetry. PMID- 1285713 TI - Microelectrode measurements of low frequency electric field effects in cells and tissues. AB - The average intensities of electric fields induced into tissue can be calculated if the morphology and conductivities of the tissue are known, and such values provide one estimate of dosage for a given field exposure level. However, the microanatomical structures of living tissue, which include gap junctions, tight junctions, highly charged cell coats, and extracellular matrices, as well as complex cell shapes, precludes a detailed characterization of the field and current distribution near the cells which are actually responding to the electric fields. This suggests that a more useful electric field dose metric may be one based on an induced physical effect on the cells. Electric fields have at least three distinct physical effects on cells: the normal plasma membrane potential will be altered; the ionic currents and ion distributions at the extracellular surface will be modified; and mechanical forces will be imposed at the cell surface. Each of these effects can, in principle, be measured through the application of specific microelectrode techniques. Here, the feasibility of using various intracellular and extracellular recording methods to obtain dosimetric values, as well as the contribution these measurements could make to our understanding of electric field interactions with biological tissue, are discussed. PMID- 1285714 TI - Voltage-sensitive dyes: measurement of membrane potentials induced by DC and AC electric fields. AB - Dye indicators of membrane potential have been available for the past 15 years and have been employed in numerous studies of cell physiology. Since the cell membrane is a likely primary site for the cascade of events resulting in a biological response to electromagnetic fields, methodologies for monitoring the membrane voltage will be critical. This laboratory has developed a series of dyes by using theoretical molecular orbital calculations to predict electrochromic structures. The spectra of electrochromic dyes are altered via a direct coupling of the molecular electronic states with an electric field. This mechanism has the advantage of providing both high temporal and high spatial resolution because the effect is instantaneous and is localized to the level of individual indicator molecules. It therefore can have significant advantages over traditional microelectrode techniques because fast changes in potential can be monitored simultaneously over many different regions of a biological preparation. We have used these dyes to monitor membrane potentials induced by both DC and AC electric fields. In a series of studies with a model membrane system, a spherical lipid bilayer, we showed that the potential develops on the membrane in good agreement with a time-dependent solution to Laplace's equation. Cell membranes can also be stained with voltage sensitive dyes. In experiments with dc fields, we are able to map the variation of the induced membrane potential along the surface of the cell by employing digital video fluorescence microscopy. We can also use the fluorescence microscope to detect membrane potential induced by ac fields by using a phase-sensitive detection scheme to extract the corresponding change in the light intensity from the fluorescent indicator. The technology can be extended to more complex biological preparations and can be used in conjunction with other optical techniques such as those which monitor intracellular ion concentrations. It may, therefore, prove highly valuable for the elucidation of biological responses to electromagnetic fields. PMID- 1285715 TI - Factors affecting neural stimulation with magnetic fields. AB - High amplitude magnetic field pulses produced by coils external to the body have been used for medical diagnosis since the mid-1980s to stimulate motor neurons in the brain cortex and peripheral nerves. While successful applications have since blossomed, it has only been during the last three years that quantitative dosimetric data have become available. The factors affecting neural stimulation can be divided into three categories broadly related to the characteristics of (i) the stimulus, (ii) the neuron, and (iii) the induced electric field as related to the configuration of the stimulating coil. The stimulus, in the case of magnetic field stimulation, has the form of an exponentially decaying pulse with a small overshoot of the opposite polarity. Physical and electrical properties of a neuron affect its electrical stimulation. Dosimetric considerations are limited to the linear model describing the threshold phenomena, where passive electrical properties and the cable model provide a reasonable approximation of neuron behavior. The electromagnetic variable responsible for stimulation is the spatial derivative of the induced electric field along the neuron axis. This paper examines the factors involved in eliciting threshold excitation of motor neurons by magnetic fields. The description of various factors is largely based on published data except for the analysis of the electromagnetic stimuli induced by various coils. PMID- 1285716 TI - Dosimetric extrapolations of extremely-low-frequency electric and magnetic fields across biological systems. PMID- 1285717 TI - Dosimetry of extremely-low-frequency magnetic fields. AB - Extrapolation of quantitative measurements across biological systems requires knowledge of field-organism interaction mechanisms. In the absence of such knowledge, one can only indicate which parameters would be important under some plausible assumptions that still lack experimental proof. In the first part of the paper it is assumed that biological effects of low intensity, extremely low frequency magnetic fields are caused by the electric fields which they induce. It is shown that detailed knowledge of electrical properties on a microscale is important to predict effects that may be due to local current density, electric field strength, surface charge distribution, and mechanical forces. In the second part of the paper, it is shown that all proposed mechanisms for direct interaction between alternating magnetic fields and cells involve also the magnitude and direction of a simultaneously present static magnetic field. Reviewed are "cyclotron resonance," quantum mechanical effects on ions weakly bound to proteins, nuclear magnetic resonance, and recent progress in magneto chemistry dealing with effects of magnetic fields of a few hundred microtesla on chemical reactions that involve free radicals. PMID- 1285718 TI - Dose-response implications of the transient nature of electromagnetic-field induced bioeffects: theoretical hypotheses and predictions. AB - Data in the literature imply that the relationship between exposure and bio effect involves more than a simple time integral of the field strength to which the living system has been subjected. Windows--ranges in which the system exhibits enhanced sensitivity--have been reported for power (or field strength), frequency, and the duration of the exposure. In this paper we show that such isolated window effects can be accounted for by recognizing the transient character of the response of the biological system. The principal assumption here is that the direct effect of the field is to increase the rates of production and degradation of mRNA or proteins. In this paper we review and extend the mathematical model that quantifies this. The model predicts that, for a given field strength, certain optimum relatively short duration exposures cause significantly larger bio-effects than exposure for much longer or much shorter times. The thinking embodied in the model should provide a framework for obtaining a meaningful working definition of "effective dose" and for predicting the response of subjects to environmental electromagnetic fields. It should help in deciding the relevant variables in the design and analysis of epidemiological studies. PMID- 1285719 TI - Regulation of cell cycle and growth control. AB - The potential biological effects of electric and/or magnetic fields on cells and tissues must be addressed systematically within a context of perturbations in cell cycle control. Such studies should not be pursued in an isolated manner but as a component of the fundamental relationship between proliferation and differentiation, the multi-step process by which structural and functional properties of specialized cells, tissues, and organs progressively develop. It is necessary to quantitatively establish the influence of electric and magnetic fields on the integrated signalling mechanisms which transduce regulatory information for 1) control of the proliferative process and 2) down-regulation of proliferation associated with the initiation of gene expression that mediates the development and maintenance of phenotypic properties characteristic of differentiated cells. We will present an overview of our current understanding of regulatory mechanisms that control proliferation and cell specialization in normal diploid cells with emphasis on rate limiting steps that may be the basis for biological perturbations by electric and magnetic fields. Addressing such questions in normal diploid cells is essential since the loss of growth control in transformed and tumor cells is accompanied by an abrogation of developmental regulatory mechanisms that are functionally coupled to proliferation. PMID- 1285720 TI - Numerical and analytical methods to determine the current density distributions produced in human and rat models by electric and magnetic fields. AB - Some numerical and analytical methods used to estimate the internal electric fields and current densities produced within human and animal models by low frequency electric and magnetic fields are surveyed. A major goal of such modeling is the design of laboratory experiments on cellular systems or animal models to produce a dosage comparable to that experienced by humans in a particular situation. Specific comparisons are made between the results of ellipsoidal approximations and finite-difference methods applied to irregularly shaped, homogeneous, human and rat models for applied 60 Hz electric (10 kV/m) and magnetic (10(-4) T) fields. For scaling purposes, the induced current densities in various parts of the body are compared for rat and human models for both types of field. In addition, the current density distribution induced in rectangular culture dishes by applied magnetic fields is also described. The extension of these methods to inhomogeneous models and localized sources may not be simple. PMID- 1285721 TI - Numerical dosimetry at power-line frequencies using anatomically based models. AB - We have used the finite-difference time-domain (FDTD) method to calculate induced current densities in a 1.31-cm (nominal 1/2 in) resolution anatomically based model of the human body for exposure to purely electric, purely magnetic, and combined electric and magnetic fields at 60 Hz. This model based on anatomic sectional diagrams consists of 45,024 cubic cells of dimension 1.31 cm for which the volume-averaged tissue properties are prescribed. It is recognized that the conductivities of several tissues (skeletal muscle, bone, etc.) are highly anisotropic for power-line frequencies. This has, however, been neglected in the first instance and will be included in future calculations. Because of the quasi static nature of coupling at the power-line frequencies, a higher quasi-static frequency f' may be used for irradiation of the model, and the internal fields E' thus calculated can be scaled back to the frequency of interest, e.g., 60 Hz. Since in the FDTD method one needs to calculate in the time domain until convergence is obtained (typically 3-4 time periods), this frequency scaling to 5 10 MHz for f' reduces the needed number of iterations by over 5 orders of magnitude. The data calculated for the induced current and its variation as a function of height are in excellent agreement with the data published in the literature. The average current densities calculated for the various sections of the body for the magnetic field component (H) are considerably smaller (by a factor of 20-50) than those due to the vertically polarized electric field component when the ratio E/H is 377 ohms. We have also used the previously described impedance method to calculate the induced current densities for the anatomically based model of the human body for the various orientations of the time-varying magnetic fields, namely from side to side, front to back, or from top to bottom of the model, respectively. PMID- 1285722 TI - Microscopic dosimetry of extremely-low-frequency electric and magnetic fields. PMID- 1285723 TI - Some engineering models for interactions of electric and magnetic fields with biological systems. AB - The objective of this paper is to review some of the fundamental mechanisms for the interaction of electric and magnetic fields with biological systems at variable levels of field strengths and to examine several possible ways by which weak fields may influence these systems. We begin with a review of the basic equations by which electric or magnetic fields interact with biological fluids and follow it with a look at the effects of inserting a simple cell membrane. The initial starting points are the force equations on charged particles and dipoles. We examine their effects on current flow, the orientation of long-chain molecules, and the forces which can be exerted by particles of magnetite on membranes. This is followed by a very simple model for the effects of a cell membrane on the overall current distribution and a model for current flow through a membrane. Some sources of nonlinearities which might serve as mechanisms for converting weak electrical signals from one frequency to a more biologically significant frequency are described. Additionally, three models by which a biological system may extract weak signals from noise are presented. The first of these is the injection-locking of oscillating processes where the signal-to-noise ratio may be less than unity. The second is parametric amplification which allows the external signal and the biological process to be at different frequencies and where stability requirements on the external pump frequency discriminates against the noise. The third approach is to examine a computer model for a neural network which can be trained to identify a 60 Hz field at signal-to-noise ratios much less than one. The key to each of these models for possible interactions of magnetic fields with biological systems is the long-term coherence of the signal with respect to the noise. Finally, we briefly examine the possibility of using scanning force and tunneling microscopes to give a better description of the characteristics of the cell surface. PMID- 1285724 TI - Assessment of conduction properties and thermal noise in cell membranes by admittance spectroscopy. AB - Advances in the speed of signal processing enable application of a Fourier synthesized function as a small perturbation (1 mV) superposed on voltage clamp steps to rapidly (< 1 sec) acquire cell membrane complex driving-point functions (impedance or admittance) in several frequency bands ranging from 1 Hz to 10 kHz. Curve fits of admittance models to these data yield a complete quantitative linear description of membrane conduction systems and their kinetics. Furthermore, the rate constants between microscopic states of an ion channel can be calculated from conductance parameters derived from model curve fits of membrane admittances. Additionally, the power spectrum of membrane thermal noise is obtainable from impedance determinations by use of the Nyquist relation. Consequently, rapid driving-point function determinations provide the most complete macroscopic assessment of membrane conduction properties presently available. Admittance determinations of the potassium conduction system in squid giant axon and the potassium conducting "inward rectifier" in snail neuron are used to illustrate the above points. PMID- 1285725 TI - Oral caffeine augmentation of ECT. PMID- 1285726 TI - Urinary lactose as an index of lactation performance. PMID- 1285727 TI - Vitamin A levels and severity of measles. New York City. AB - Recent studies show that vitamin A levels decrease during measles and that vitamin A therapy can improve measles outcome in children in the developing world. Vitamin A levels of children with measles have not been studied in developed countries. We therefore measured vitamin A levels in 89 children with measles younger than 2 years and in a reference group in New York City, NY. Vitamin A levels in children with measles ranged from 0.42 to 3.0 mumol/L; 20 (22%) were low. Children with low levels were more likely to have fever at a temperature of 40 degrees C or higher (68% vs 44%), to have fever for 7 days or more (54% vs 23%), and to be hospitalized (55% vs 30%). Children with low vitamin A levels had lower measles-specific antibody levels. No child in the reference group had a low vitamin A level. Our data show that many children younger than 2 years in New York City have low vitamin A levels when ill with measles, and that such children seem to have lower measles-specific antibody levels and increased morbidity. Clinicians may wish to consider vitamin A therapy for children younger than 2 years with severe measles. Additional studies of vitamin A in measles and other infectious diseases, and in vaccine efficacy trials, should be done. PMID- 1285728 TI - Long-term follow-up of acute partial transverse myelopathy. AB - We carried out a prospective, long-term, combined clinical and MRI follow-up study on 15 patients hospitalized at the Montreal Neurological Institute between 1985 and 1988 with a diagnosis of acute partial transverse myelopathy of unknown etiology. Twelve of the 15 (80%) developed clinically definite or lab-supported definite multiple sclerosis (MS) by the end of a mean follow-up period of 38.5 months. The presence of CNS periventricular white matter lesions by cranial MRI at onset increased the likelihood of development of MS to 93%. PMID- 1285729 TI - Is a woman responsible for being pregnant? Another discussion about the morality of abortion. PMID- 1285730 TI - Pelvic pain without pelvic organs. AB - We report on 4 patients with persistent, severe pelvic pain unresponsive to removal of the bladder, uterus, ovaries and fallopian tubes. Of the patients 3 had a diagnosis of interstitial cystitis and 1 had voiding dysfunction. We conclude that severe pelvic pain may not be responsive to the elimination of pelvic organs and alternative organ-preserving therapies should be considered. PMID- 1285731 TI - High-dose chemotherapy with autologous bone marrow transplantation for the treatment of metastatic breast cancer. AB - PURPOSE: This review was undertaken to examine the evidence of effectiveness of high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) for the treatment of metastatic breast cancer and to compare the magnitudes of the benefits and harms of HDC/ABMT with those of conventional doses of chemotherapy. DESIGN: Published studies were reviewed and analyzed. RESULTS: No randomized controlled trials have been published that evaluate HDC/ABMT. Only one internally controlled study has been conducted; it demonstrated that HDC/ABMT and conventional treatment have virtually identical outcomes. Comparisons of uncontrolled clinical series are confounded by patient selection and other biases. Gross comparisons indicate that, compared with conventional-dose chemotherapy, HDC/ABMT achieves (1) higher complete response rates (36% v 8%), (2) higher overall response rates (70% v 39%), (3) similar median response durations (8 months v 9.6 months), (4) similar median survival durations (16 months v 16.6 months), and (5) similar overall survival rates (eg, 43% 2-year survival v 39%). Observations of cases with longer-term disease-free survival are promising but not conclusive. High-dose chemotherapy with ABMT has a higher treatment-related mortality rate (5% to 15% v 1%), a high rate of nonmortal toxicity (approximately 30%), and a high rate of side effects (approaching 100%). CONCLUSIONS: Firm conclusions are not possible because of the lack of controlled studies and the presence of numerous biases. However, the existing evidence does not demonstrate that HDC/ABMT is superior to conventional-dose chemotherapy for the treatment of metastatic breast cancer. Randomized controlled trials are needed. PMID- 1285733 TI - Possible association of malignant hyperthermia with sevoflurane anesthesia. PMID- 1285732 TI - Disseminated candidiasis due to amphotericin B-resistant Candida albicans. AB - Although development of resistance in Candida albicans to amphotericin B is considered rare, C. albicans was persistently recovered from a 28-year-old man after a prolonged course of broad-spectrum antimicrobial therapy for a pancreatic abscess. Determination of the MICs of drugs for C. albicans in Sabouraud broth revealed MICs of 2.5 mg/l amphotericin B, greater than 40 mg/l ketoconazole, 2.5 mg/l miconazole, and greater than 40 mg/l 5-fluorocytosine. Synergy testing revealed a MIC of 0.3 mg/l amphotericin B in the presence of 2.5 mg/l 5 fluorocytosine. When intravenous 5-fluorocytosine was added to the patient's antifungal regimen, achieving levels of 125 mg/l, negative blood cultures resulted for the first time. This suggests there may be a clinical use for in vitro synergy testing as an adjunct to guide antifungal therapy for fungemia due to amphotericin B-resistant C. albicans. PMID- 1285734 TI - 'Post mortem identification of a body by use of dental evidence'. PMID- 1285735 TI - Mandatory drug testing: boon for public safety or launch of a witch-hunt? PMID- 1285736 TI - Glue ear and grommets. PMID- 1285737 TI - Prediction of mortality in patients with cystic fibrosis. AB - BACKGROUND: The majority of patients with cystic fibrosis die in early adulthood of lung disease. Lung transplantation is a treatment option for patients with advanced pulmonary disease, although the waiting period for organs may be as long as two years. Our purpose was to determine whether the risk of death due to respiratory failure could be predicted one or two years in advance on the basis of pulmonary function, blood gas levels, and nutritional status. METHODS: The study cohort consisted of 673 patients followed between 1977 and 1989. In each patient, pulmonary function, blood gas levels, nutritional status, and vital status were assessed between 1977 and 1987. Cox proportional-hazards regression analysis was used to compute the relative risk of death within one or two years after particular measurements. The effects of age and sex on mortality were also included in the analysis. RESULTS: One hundred ninety patients (28 percent) died during the study period. Overall, patients with a forced expiratory volume in one second (FEV1) less than 30 percent of the predicted value, a partial pressure of arterial oxygen below 55 mm Hg, or a partial pressure of arterial carbon dioxide above 50 mm Hg had two-year mortality rates above 50 percent. Among the laboratory measurements, the FEV1 was the most significant predictor of mortality, but age and sex were also significant in predicting risk. After adjustment for age and sex, the relative risk of death within two years was 2.0 (95 percent confidence interval, 1.9 to 2.2) for each decrement in the FEV1 of 10 percent below the predicted value. Among patients with the same FEV1, the relative risk of death was 2.0 (95 percent confidence interval, 1.5 to 2.6) in patients 10 years younger than other patients, and 2.2 (1.6 to 3.1) in female patients as compared with male patients. CONCLUSIONS: Patients with cystic fibrosis should be considered candidates for lung transplantation when the FEV1 falls below 30 percent of the predicted value. Female patients and younger patients may need to be considered for transplantation at an earlier stage. PMID- 1285738 TI - Resistance to injection: 1991 RD Lawrence Lecture. PMID- 1285739 TI - Angiomyolipoma of the kidney: a clinical enigma in diagnosis and management. AB - Renal angiomyolipomas are uncommon benign tumours which clinically mimic renal cell carcinoma. They have characteristic features on ultrasound and CT scanning which may enable their diagnosis preoperatively. We review our experience of six cases of renal angiomyolipoma. These cases highlight the difficulties in making a preoperative diagnosis despite the use of modern scanning. We advocate conservative resection when the diagnosis is made preoperatively and when technically possible, but radical nephrectomy should be performed if there is a possibility of a carcinoma. PMID- 1285740 TI - No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study. AB - PURPOSE: The purpose of this study is to evaluate the risk of acute vascular events in patients receiving cisplatin-based chemotherapy for testicular cancer. PATIENTS AND METHODS: A questionnaire assessing cardiovascular toxicity was distributed to all participants in the Testicular Cancer Intergroup study and details of toxicity from the chemotherapy flow sheets were reviewed. Patients with pathologic stage I testicular cancer were registered on to the study and observed after retroperitoneal lymphadenectomy. Patients with pathologic stage II disease were randomized to receive two postoperative courses of adjuvant cisplatin-based chemotherapy or observation. Any patient who had disease recurrence after observation or adjuvant therapy was given four cycles of cisplatin-based chemotherapy. RESULTS: Review treatment-related toxicity for those patients receiving adjuvant chemotherapy (n = 97) or chemotherapy for recurrent disease (n = 83) showed no cases of acute cardiovascular toxicity. The median follow-up period after study enrollment was 5.1 years; 459 questionnaires were mailed and 270 were returned. The percent return was equal among the observed adjuvant and recurrent groups (59%, 54%, and 64%). There was a significant increase in the incidence of extremity paresthesias in the two groups receiving chemotherapy. Fatal myocardial infarction was reported in two patients in the observation group and one nonfatal infarction was reported in the adjuvant treatment group. No patient in any group reported an incidence of stroke. Three patients in the observation group and one patient in the recurrent group experienced a thromboembolic event. CONCLUSION: Despite sporadic case reports suggesting a causal association between chemotherapy for testicular cancer and acute vascular events, this retrospective analysis provides no evidence of an increased risk for subsequent cardiovascular disease in this patient population. PMID- 1285741 TI - The problem with futility. PMID- 1285742 TI - The use of intrasite gel in healing open sternal wounds. PMID- 1285744 TI - Legal standards for an appropriate education in the post-Rowley era. AB - In 1982 the U.S. Supreme Court held than an appropriate education under the Individuals with Disabilities Education Act was one that was formulated in accordance with the Act's procedures and that conferred some educational benefit on students with disabilities. Initially, the lower court applied this terminology strictly and approved any proposed individualized education program that conferred even minimal educational benefit. However, later courts began to take a more liberal approach and held that the educational program must confer some meaningful benefit. A careful reading of the Supreme Court's 1982 decision indicates that this recent approach is consistent with Congress's and the Court's intent. The Court never intended to establish one test of appropriateness since it recognized that some flexibility was needed to determine what would be appropriate for a diverse population of students with disabilities. PMID- 1285743 TI - Ethnic differences in family factors related to early drug initiation. AB - The literature on family predictors of substance use for the general population is reviewed and compared to findings for three specific ethnic groups: black, white and Asian Americans. Rates of substance use initiation are examined in a sample of 919 urban 5th-grade students. Ethnic differences on measures of family predictors are examined and significant ethnic differences are found on several of these factors. Finally, separate regressions for black, white and Asian American youths of family factors on the variety of substances initiated examine ethnic similarities and differences in predictors. The results demonstrate significant differences by ethnicity in family management practices, involvement in family activity, sibling deviance, parental disapproval of children's drinking and family structure. The regression equations identified unique as well as common predictors of the variety of substances initiated by the end of 5th grade. Implications of the results are discussed. PMID- 1285745 TI - Retroclival arachnoid cyst. AB - Retroclival arachnoid cyst is a rare mass lesion, with only seven cases previously reported in literature. MR is the imaging modality of choice in its evaluation and in its differentiation from epidermoid cyst. The case reported here was surgically proved and had an uncharacteristic MR signal intensity that was higher than that of cerebrospinal fluid due to previous hemorrhage. PMID- 1285746 TI - Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. AB - BACKGROUND: Effective hand-washing can prevent nosocomial infections, particularly in high-risk areas of the hospital. There are few clinical studies of the efficacy of specific hand-cleansing agents in preventing the transmission of pathogens from health care workers to patients. METHODS: For eight months, we conducted a prospective multiple-crossover trial involving 1894 adult patients in three intensive care units (ICUs). In a given month, the ICU used a hand-washing system involving either chlorhexidine, a broad-spectrum antimicrobial agent, or 60 percent isopropyl alcohol with the optional use of a nonmedicated soap; in alternate months the other system was used. Rates of nosocomial infection and hand-washing compliance were monitored prospectively. RESULTS: When chlorhexidine was used, there were 152 nosocomial infections, as compared with 202 when the combination of alcohol and soap was used (adjusted incidence-density ratio [IDR], 0.73; 95 percent confidence interval, 0.59 to 0.90). The largest reduction with chlorhexidine was in gastrointestinal infections (IDR, 0.19; 95 percent confidence interval, 0.05 to 0.64). When chlorhexidine was available, the rates of nosocomial infection declined in each of the ICUs, and health care workers washed their hands more often than when alcohol and soap were used (relative risk, 1.28; 95 percent confidence interval, 1.02 to 1.60). The total volume of alcohol and soap used was 46 percent that of chlorhexidine (P less than 0.001). CONCLUSIONS: A hand-disinfection system using an antimicrobial agent (chlorhexidine) reduces the rate of nosocomial infections more effectively than one using alcohol and soap. The improvement may be explained at least in part by better compliance with hand-washing instructions when chlorhexidine was used. PMID- 1285747 TI - The use of aspirin in ischemic heart disease. PMID- 1285748 TI - Changes in community psychiatry during the past 50 years. PMID- 1285749 TI - The Disability Support Pension and the "new maths". PMID- 1285750 TI - Bovine spongiform encephalopathy and risk to health. PMID- 1285751 TI - Glove powder as a contact allergen. PMID- 1285752 TI - Histopathological changes in the coeliaco-mesenteric ganglia of horses with 'mal seco', a grass sickness-like syndrome, in Argentina. AB - 'Mal seco' is a grass sickness-like syndrome of horses in Argentina. A histopathological study was made of the coeliaco-mesenteric ganglia of four horses with 'mal seco' and of four horses that died from other causes. The severity and extent of the lesions found in the horses with 'mal seco' was greatest in the two with the shortest clinical course. Degenerative changes consisted mainly in the loss of Nissl substance, cytoplasmic vacuoles, neuronophagia, intercellular and intracytoplasmic eosinophilic bodies, and pyknotic and eccentric nuclei. The coeliaco-mesenteric ganglia of the control horses had no histological lesions. The histological lesions in the horses with 'mal seco' were very similar to those described in the coeliaco-mesenteric ganglia of horses with grass sickness in Europe and it is suggested that 'mal seco' and grass sickness may be the same disease. PMID- 1285753 TI - Validating the SF-36 health survey questionnaire: new outcome measure for primary care. AB - OBJECTIVES: To test the acceptability, validity, and reliability of the short form 36 health survey questionnaire (SF-36) and to compare it with the Nottingham health profile. DESIGN: Postal survey using a questionnaire booklet together with a letter from the general practitioner. Non-respondents received two reminders at two week intervals. The SF-36 questionnaire was retested on a subsample of respondents two weeks after the first mailing. SETTING: Two general practices in Sheffield. PATIENTS: 1980 patients aged 16-74 years randomly selected from the two practice lists. MAIN OUTCOME MEASURES: Scores for each health dimension on the SF-36 questionnaire and the Nottingham health profile. Response to questions on recent use of health services and sociodemographic characteristics. RESULTS: The response rate for the SF-36 questionnaire was high (83%) and the rate of completion for each dimension was over 95%. Considerable evidence was found for the reliability of the SF-36 (Cronbach's alpha greater than 0.85, reliability coefficient greater than 0.75 for all dimensions except social functioning) and for construct validity in terms of distinguishing between groups with expected health differences. The SF-36 was able to detect low levels of ill health in patients who had scored 0 (good health) on the Nottingham health profile. CONCLUSIONS: The SF-36 is a promising new instrument for measuring health perception in a general population. It is easy to use, acceptable to patients, and fulfils stringent criteria of reliability and validity. Its use in other contexts and with different disease groups requires further research. PMID- 1285754 TI - Barcelona's asthma epidemics: clinical aspects and intriguing findings. PMID- 1285755 TI - Leprosy vaccine. PMID- 1285756 TI - Glutaraldehyde dilution in an automatic washer. PMID- 1285758 TI - Osteopathy: the 'orthodox' alternative. PMID- 1285757 TI - Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease? PMID- 1285760 TI - 'Orthodontic relapse'. PMID- 1285759 TI - Eye care in general practice. PMID- 1285761 TI - Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. PMID- 1285762 TI - If A-B does not predict heart disease, why bother with it? A clinician's view. AB - Ray asks the question: 'If A-B does not predict heart disease, why bother with it?' (British Journal of Medical Psychology, 64 (1) 1991). Having worked for several years in prevention of heart attack recurrence, I am inclined to agree with his conclusion that the construct is a trail which should now be abandoned. Grief, hostility and social isolation, fear and work demands have each been implicated in heart disease independently of Type A. PMID- 1285763 TI - Acute leukemia with t(8;21) can express T-lineage-associated markers. PMID- 1285764 TI - Cardiac rehabilitation programmes: are women less likely to attend? PMID- 1285765 TI - Treatment of natal cleft sinus. PMID- 1285766 TI - Renal transplantation in tuberous sclerosis. PMID- 1285767 TI - Frequency of citation and outcome of cholesterol lowering trials. PMID- 1285768 TI - Validating the SF-36. PMID- 1285769 TI - Human milk banks. PMID- 1285770 TI - Back testing devices. PMID- 1285771 TI - Intramuscular vitamin K and childhood cancer. PMID- 1285772 TI - The transient voltage surge suppressor. PMID- 1285774 TI - Radiation damage to mouse skin and oesophagus. PMID- 1285773 TI - Rapid tranquillisation. PMID- 1285775 TI - Long-term beds for children? PMID- 1285776 TI - Remains identification by frontal sinus radiographs. PMID- 1285777 TI - Angiostrongylus cantonensis. PMID- 1285778 TI - Gitelman syndrome and hypocalciuria. PMID- 1285779 TI - Integrating psychology into nursing practice. PMID- 1285780 TI - Depletion of glutathione in normal and malignant human cells in vivo by L buthionine sulfoximine: possible interaction with ascorbate. PMID- 1285781 TI - Re: Decrease in renal vascular resistance in University of Wisconsin solution preserved kidney transplants. PMID- 1285782 TI - Survival rates with coronary artery disease for black women compared with black men. AB - OBJECTIVE: To evaluate the influence of gender on the prognosis of coronary heart disease among black patients. DESIGN: Cohort study based on a consecutive sample from a hospital registry, with a mean follow-up of 4 years. SETTING: An inner city public hospital in Chicago, Ill. PATIENTS: The study included 1719 consecutive black patients (780 men and 939 women) who had any one of the following events: cardiac catheterization for presumed coronary heart disease, hospitalization for acute myocardial infarction, or coronary artery bypass grafting. RESULTS: Hospital and operative mortality rates following acute myocardial infarction and coronary artery bypass grafting were similar between the two sexes. The relative risks for cardiac death in women vs men were 0.88 (95% confidence interval [CI], 0.60 to 1.28), 0.79 (95% CI, 0.53 to 1.17), and 0.79 (95% CI, 0.34 to 1.85) for coronary artery disease, acute myocardial infarction, and coronary artery bypass grafting, respectively, after adjusting for age, history of diabetes, hypertension, angina pectoris and myocardial infarction, number of diseased vessels, and ejection fraction. Compared with patients of the same sex with normal angiograms, relative risk estimates were 5.0, 10.1, and 6.3 for women and were 1.8, 4.0, and 2.0 for men in the same three groups of patients, respectively. CONCLUSIONS: Survival with coronary artery disease in black women is similar to that observed in black men, but relative to members of the same sex without the disease, the prognosis for women is considerably worse than for men. PMID- 1285783 TI - "Futility" as a criterion in limiting treatment. PMID- 1285784 TI - Use of psychoactive drugs in nursing homes. PMID- 1285785 TI - Correction: calcium-channel blockers in primary pulmonary hypertension. PMID- 1285786 TI - Underestimation of the incidence of mental retardation. PMID- 1285787 TI - A note on the calculation of expected survival, illustrated by survival of liver transplant patients by B.L. Thomsen, N. Keiding and D.G. Altman, Statistics in Medicine, 10, 733-738 (1991) PMID- 1285788 TI - Mandatory testing for AIDS is no guarantee. PMID- 1285789 TI - White cell reduction in platelet concentrates. PMID- 1285790 TI - Treatment of water intoxication with mannitol. PMID- 1285791 TI - Role of 17 beta-estradiol and tamoxifen in induction of endometrial carcinoma in experimental animal model: nude mice. PMID- 1285792 TI - Oral versus intravenous caffeine augmentation of ECT. PMID- 1285793 TI - Caloric requirements for weight maintenance: a British viewpoint. PMID- 1285794 TI - Amobarbital interview for catatonic patients. PMID- 1285796 TI - More on epidural fentanyl analgesia. PMID- 1285795 TI - Propofol in cardiac catheterization. PMID- 1285797 TI - Through the canopy glass: a comparison of injuries in naval aviation ejections through the canopy and after canopy jettison, 1977 to 1990. PMID- 1285799 TI - The Disability Support Pension and the "new maths". PMID- 1285798 TI - Expression of a chimeric CaMV 35S Bacillus thuringiensis insecticidal protein gene in transgenic tobacco. AB - Insecticidal transgenic tobacco plants containing a truncated Bacillus thuringiensis cryIA(b) crystal protein (ICP) gene expressed from the CaMV 35S promoter were analyzed for ICP gene expression under field and greenhouse conditions over the course of a growing season. We present new information on temporal and tissue-specific expression of a CaMV 35S/cryIA(b) gene. Levels of cryIA(b) protein and mRNA were compared in both homozygous and hemizygous lines throughout plant development. Levels of ICP mRNA and protein increased during plant development with a pronounced rise in expression at the time of flowering. Homozygous ICP lines produced higher levels of ICP than the corresponding hemizygous lines. ELISA analysis of different tissues in the tobacco plant showed ICP gene expression in most tissues with a predominance of ICP in older tissue. All transgenic ICP tobacco lines which were studied in the field and greenhouse contained 400 ng to 1 microgram ICP per gram fresh weight in leaves from the mid section of the plant at flowering. The amounts of ICP produced by field lines were directly comparable to levels observed in greenhouse-grown plants. PMID- 1285800 TI - Change "DNR" to "GPC". PMID- 1285801 TI - Speciation events. PMID- 1285802 TI - Anal sex and AIDS. PMID- 1285803 TI - Coping with toxic pulses. PMID- 1285804 TI - Visual evoked potentials and intracranial pressure. PMID- 1285805 TI - ERS annual congress. Vienna, Austria, August 29-September 3, 1992. Abstracts. PMID- 1285806 TI - Western blotting is a sensitive technique for the detection of anti-PlA1. AB - Western (immuno-) blotting was evaluated as a technique for anti-PlA1 detection, using untreated and chloroquine or low pH-treated platelets. Chloroquine-treated platelet membranes generated the cleanest blots, giving end-point titres of 4000 16,000 for three different anti-PlA1 sera. These titres were between three and eight doubling dilutions higher than those obtained in solid phase, ELISA or indirect immunofluorescence tests. Nitrocellulose strips used for blotting could be stored for at least six months at room temperature without significant loss of PlA1 activity. However, immunoblotting still failed to detect anti-PlA1 in the sera of four of fivePl (A1-) women whose infants were born with neonatal thrombocytopenia of probable alloimmune origin. PMID- 1285808 TI - Draft: Professional education in audiology position statement. Ad Hoc Committee on Professional Education in Audiology. PMID- 1285807 TI - (1-Sar, 8-Ile) angiotensin II in the treatment of inhalation injury: a pilot study. AB - The patients were three men and two women with moderate to severe inhalation injury. Each patient received immediate fluid therapy and all required intubation for respiratory management. At some time between 24 and 72 hours after the injury, the synthetic angiotensin analogue (1-Sar, 8-Ile) angiotensin II was infused at a rate of 100 ng/kg/min for 10 minutes, 200 ng/kg/min for another 10 minutes, and 300 ng/kg/min for 30 minutes. The mean (+/- SD) PaO2 increased from 80.8 +/- 26.9 mmHg before to 89.8 +/- 27.3 mmHg after the infusion (P < 0.05) and the PaCO2 decreased from 42.4 +/- 8.3 to 39.6 +/- 7.9 mmHg (P < 0.05). A transient pressor response was noted in all patients. The results suggest that this angiotensin II analogue may be of benefit in the treatment of inhalation injury and other types of acute lung injury. PMID- 1285809 TI - Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification. AB - The ability to identify large numbers of yeast artificial chromosomes (YACs) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). We describe a method of preparing region-specific single stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region. PMID- 1285810 TI - Distribution of filipin-sterol complexes in the bloodstream form of Trypanosoma brucei gambiense. AB - The polyene antibiotic, filipin, was used as a probe for demonstrating sterols in the plasma membrane of Trypanosoma brucei gambiense. Three different regions of the continuous plasma membrane over the cell body proper, flagellar pocket, and flagellum, were compared as to density and distribution of the filipin-sterol complexes by freeze-fracture method. The density of the complexes was highest in the cell body membrane and lowest over the flagellar pocket. The filipin-sterol complexes in the cell body membrane were distributed homogeneously on both the protoplasmic and exoplasmic faces except in the zone of flagellar attachment. This junctional zone showed a linear, complex-poor region. In the flagellar membranes, a line of complex-poor regions was observed along the juncture of the flagellum to the cell body. At the neck of the flagellar pocket, the membranes of the flagellar pocket and flagellum were closely opposed, with few filipin-sterol complexes on either membrane. At the base of the flagellar shaft, the complexes were completely lacking on both faces. Based on these observations, the zones of juncture observed in T.b. gambiense seems to be similar in ultrastructure to mammalian cell junctions, such as tight, gap, septate junctions and desmosomes, which show a nearly complete absence of the filipin-sterol complexes. PMID- 1285811 TI - [Collection of anti-HBs hyperimmune plasma: stimulation by Genhevac B in weakly immunized donors]. AB - The need for anti HBs globulin is still important in spite of the development of the HBs vaccination. Twenty-two plasma donors, immunized against Hepatitis B virus (HBV) with titers of anti HBs between 100 and 6,000 milli International Units per ml (mUI/ml), received two injections of Genhevac B Pasteur at a one month interval, and a third injection two months later whenever the answer was still under 6,000 mUI/ml, which is the minimum necessary in order to obtain a specific globulin compatible with the National Standard (100 UI/ml) from plasma fractions. In this programme, no severe adverse reaction was documented, and the mean rate of anti HBs rose from 1,322 to 35,173 mUI/ml, with a mean multiplying factor of 20.2. This result was reached after the first injection in "responders"; the third injection did not increase the titer in "non responders". The titer was still above 6,000 mUI/ml after six months in all the donors with more than 1,500 mUI/ml before vaccination. This limit is suggested to select plasma donors for vaccination, and a booster injection could be proposed every six months. PMID- 1285813 TI - Classification of accidents in the Arctic. A suggestion for adaptation of the Nordic classification for accident monitoring. AB - Since 1980 the Nordic Medico-Statistical Committee (NOMESCO) has supported the development of the Classification for Accident Monitoring. The objective of the Classification is to provide the foundation for accident prevention. In agreement with the purpose of NOMESCO to establish comparable medical statistics in the Nordic countries, it is considered how the Nordic Classification might be adapted to conditions in Arctic areas, in order also to facilitate accident prevention in these areas. The Classification is multiaxial and describes place of occurrence, injury mechanism, activity (of victim), products involved in accidents, and information of special relevance to traffic accidents and occupational accidents. The hierarchical build-up of the coding system allows subspecification of the variables mentioned above, thus enabling the system to contain such information which is suggested for Arctic areas, and at the same time preserving the comparability of data at an aggregated level. Further development is suggested in a plan of work. PMID- 1285812 TI - [Role of the ABO system in transplants and grafts]. AB - The structures and locations of the glucidic molecules in the ABO system vary according to the tissues, ontogenesis and individuals. Although their physiological role is not well established, they are considered as very important factors in transplantations. When the ABO identity is not taken into account, hyperacute, acute, and chronic rejections, or hemolysis and tolerance phenomenon may occur but the incidence of these problems varies according to the tissues. In ABO minor mismatch, the transplantation is always possible, but is associated with worse long term graft survival, except for bone marrow. In ABO major mismatch, the frequency of hyperacute rejections remains the main problem, although the frequency is nil for bone marrow, very low for the liver, quite important for the kidney, and high for heart transplantations. Thus, the ABO group barrier is not absolute but must still be taken into account for allogenic transplantations. PMID- 1285814 TI - Fatal non-intentional injuries in Greenland. AB - Accidents are one of the main killers in Greenland, responsible for 16% of deaths but 34% of potential years of life lost (PYLL). During 1968-89, 1310 deaths from accidents were recorded, equivalent to a mortality rate of 118 per 100,000 person years-more than six times higher than in Denmark. There was a decreasing secular trend but only for certain types of accidents. Mortality rates were considerably higher in indigenous Greenlanders than in Danes, higher in males than in females and higher in settlements than in towns. Most accidents were related to the Greenlandic life style with drowning and boat accidents responsible for 45% of all fatal accidents, and injuries due to fire, cold, firearms or bites of dogs responsible for 23%. In certain age groups and in particular in females, at least 60% of the fatal accidents were alcohol related. PMID- 1285816 TI - National registration of accidents in Iceland. AB - Community based registration of accidents has been employed in Iceland from 1987. A form developed in the emergency ward at the city Hospital of Reykjavik has been used for the registration. The following issues have been registered: the type and the seriousness of the injury, treatment, place of accident and time of accident. Health centres in Iceland have been computerized from 1976. At the time being about half of the health centres participate in the registration with the information included in the form as the source. Every health center has its well defined district. The accidents among the inhabitants in each district is registered, while accidents among other people, e.g. tourists, is registered separately. At this moment 183,000 out of a total number of 259,000 inhabitants are covered by the registration, i.e. 71% of the population. In 1989 the frequency of accidents was 198 per 100,000 inhabitants. 26% of the accidents occurred at home, 11% at work, 9% during physical activity, 6% was traffic accidents, whereas the same proportion occurred at school. This registration system has been created as a result of annual conferences on accidents arranged by the Director General of public health since 1984. Representatives for the following parties have been invited; medical doctors working in hospitals and health centres, clinical nurses, physiotherapists, the National Insurance Service, other insurance companies, rescue and ambulance personal, fire departments, the Automobile Association, the communication Council. Local communities members of the parliament, voluntary organizations, e.g. Red Cross, the Sea Rescue Service and the Aviation Board. This activity has stimulated measures aiming at preventing accidents in several local communities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285815 TI - Accident toll in a Norwegian Spitsbergen mining community. AB - The coal mining community of Longyearbyen suffered a total loss of 84 persons in fatal accidents during the 40-year period from 1950 to 1989. Up to the beginning of the 1970's the great majority of injuries causing death were related to coal mining. In the 20-year period from 1970-1989 14 people died in occupational accidents. 24 were killed during off-work hours. The male population, averaging, 776 individuals through the observation period, run a risk of being involved in a fatal leisure-time accident nearly 3 times that of age-matched groups on the Norwegian mainland. Potential years of life lost for the Spitsbergen group were estimated to be of a magnitude 2.6 times that of the mainland. The females are even worse off with a risk of having a fatal accident which is 18 times higher. Occupational deaths in the mines were nearly 2 times as frequent as in the mines on the Norwegian mainland. We have moved a long way towards the control of fatal occupational accidents. The rise in non-occupational fatal injuries means, however, that the overall safety gain is meagre. PMID- 1285817 TI - Injuries in the Alaskan Arctic. AB - In recent years, the State of Alaska has developed a Trauma Registry data collection system on injuries which result in hospitalization or death. All 25 acute care hospitals in Alaska have agreed to participate in this Trauma Registry. Data are presented from this registry on injuries which occurred between March 1988 and December 31, 1990 in the North Slope Borough, the Northwest Arctic Borough, and the Norton Sound Region. Causes of death and serious injury are presented and comparisons made among regions and between Natives (primarily Inupiat Eskimos) and non-Natives. Use of firearms accounted for the majority of fatalities (32%), while falls were the most reported injury (19%). Trauma Registry Data can be used to target high risk groups and activities for the development and evaluation of prevention programs. This database also is used for quality assurance reviews of patient care and outcomes. PMID- 1285818 TI - Epidemiology of injuries in northern areas. AB - Traumatic injuries are among the leading causes of death in Alaska and the arctic. Intentional injuries (homicide and suicide) and unintentional injuries (motor vehicle crashes, drowning, aviation crashes, alcohol and other drugs) cause 29% of all deaths and 53% of all years of potential life lost (YPLL) in Alaskans. Mortality and morbidity rates due to injuries remain higher among Alaska Natives than other racial groups. The occupational fatality rate in Alaska (33 deaths per 100,000 workers) is the highest in the United States and is largely due to the large number of deaths among commercial fishermen, airplane pilots, sailors, truck drivers, and loggers. Effective injury control and prevention efforts are hampered by lack of adequate surveillance systems. Injury research and public health control measures are unfocused, lack continuity, and are undersupported. PMID- 1285819 TI - Accidents in the north. Some aspects on snowmobile accidents and moose-car collisions. AB - Snowmobile accidents and moose-car crashes are typical accidents in Northern Sweden. In this region there is about 1 snowmobile/10 inhabitants. The present paper combines previously published studies. The studies on snowmobile accidents are based on a material comprising all 61 fatally injured snowmobile drivers from the four northern counties of Sweden during the period 1973-1987. The helmet usage was analyzed in two clinical study populations including 200 injured from the county of Vasterbotten from two periods 1979-1980 and 1985-86. Of the fatally injured (median age 32 years) 86% were driving under the influence of alcohol with a mean blood alcohol concentration of 0.17 g/ml. Serious head injuries were uncommon among persons driving without a helmet in the clinical material. Only in about 6% of the cases an open face helmet would probably have had an injury reducing effect. Drunken driving is an important etiological factor for fatal snowmobile accidents. Preventive measures must include information that the Traffic Temperance Law also applies to snowmobile riding. A helmet law for snowmobile riders does not seem to be motivated from the injury reduction point of view. According to official Swedish police statistics more than 400 car occupants are injured annually in crashes with a moose. The crash mechanism is special. Because of its long legs the body of the moose hits directly against the windshield, windshield pillars and front roof. During a period of three years 154 injured passenger car occupants were treated in the hospitals in Umea and Skelleftea. Of both the front and rear seat occupants 80% suffered laceration injuries from glass or glass splinters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285820 TI - Prevention of accidents in reindeer herding work. AB - In the northern part of Finland we have about 450,000 reindeer and their raising gives work to about 3,500 reindeer herders. In this study data on the occupational accidents of herders were collected by two questionnaires with an interval of 2 years. Based on the surveys of accident risks in various work phases 34 preventive measures were developed and information about them was passed on to the herders between the questionnaires. Most of the accidents occurred in the late autumn during slaughtering, gathering for separation and during separation work. The main causes of accidents were the slaughtering knife (30%) and the reindeer itself (25%). The most serious accidents were caused by snowmobiles and other terrain vehicles. The recommended preventive measures mostly dealt with the environment of permanent working places, personal protection and working habits. The follow-up questionnaire showed that the herders had implemented on an average 5.8 preventive measures. The incidence rate of accidents also decreased during the 2 years from 21 to 12 accidents/1000 working days. In conclusion these results show that it is possible to develop measures preventing accidents and to improve the safety in reindeer herders' work. PMID- 1285821 TI - Snowmobile accidents in Lapland. AB - It is assumed that there are about 30,000 snowmobiles in Lapland. In 12 health centers and in all three hospitals the snowmobile accidents were analyzed in 1990. There were 290 accidents reported. Seventy-two percent were leisure time accidents. The accidents occurred typically in the afternoon during the weekend in the spring. Most accidents took place in the woods by driving into a barrier. Half of the injuries were on extremities, especially on legs. Eighteen % were head injuries and 11% thorax injuries. According to the Abbreviated Injury Scale classification most injuries were of class 1 and 2. There were 5 deaths. Thirty one % of the injured persons had a helmet. From 1991 the use of the helmet is compulsory. The registration of snowmobiles is important and it should be implemented in Finland. The snowmobile is a significant cause of accidents in Lapland today and preventive measures are urgent. PMID- 1285822 TI - Accidents in the Arctic. A psychological point of view. AB - The aim of this paper is to discuss the influence of arctic conditions on the occurrence of accidents especially from the point of view of the interaction between environment, activity and man. Special attention is paid to risk assessment, risk taking and risk compensation. According to the danger factor theory frostbites should be extremely common in arctic regions, but in reality serious frostbites appear rarely in accident statistics. This finding supports the interactive accident theories. Instead cold can be a contributing factor in accident and injury causation and the effect of cold is most often indirect. Frostbites can occur e.g. as a result of an accident, losing one's way because of darkness, snow storm etc., wet clothes, unexpected temperature changes, disease attack, alcohol-induced reasons such as immobility or excess risk taking etc. Temperatures below and above +20 degrees C increase unsafe behavior. In the Arctic it is impossible to remove all the potentially dangerous factors, because many typical features of working and living conditions are regulated by natural forces, the seasons etc. This makes accurate risk assessment and prediction especially important in accident prevention. If the person does not recognize the situations in which the risk factors exist, he/she cannot implement precautionary steps at the right moment and hence cannot avoid risks. Moreover, if better and safer machines, equipment and tools get people to take greater risks, the accident situation can even become worse. PMID- 1285824 TI - Occupational safety and health training in Alaska. AB - We have eleven years of experience delivering a wide variety of worker education programs in cross-cultural settings to reduce the levels of occupational fatalities and injuries in Alaska. We published an instructional manual and informational poster for workers, on Alaska's "Right-To-Know" law regarding chemical and physical hazards. The "Job Hazard Recognition Program" curriculum for high school students has received national acclaim for being proactive in dealing with worker safety education before the student becomes a member of the work force. Adult educational programs and materials have been designed to include less lecture and formal presentation, and more practical "hands on" and on-the-job experience for specific trades and hazards. New industry specific manuals deal with hazardous waste reduction as a method to reduce harm to the employee. Difficulty in getting instructors and training equipment to rural locations is dealt with by becoming creative in scheduling classes, using locally available equipment, and finding regional contacts who support the overall program. Alternative approaches to funding sources include building on regional long-term plans and establishing complementary program objectives. PMID- 1285823 TI - Safety in the use of four-wheeled all-terrain vehicles in Finland. AB - The aim of this study was to ascertain the use of four-wheeled all-terrain vehicles in Finland and estimate the safety in driving a four-wheeler. According to the importers there are about 3,000 four-wheelers in use in Finland. A questionnaire was sent to the owners of four-wheelers (n = 185), in which questions were asked about their use, protection used when driving, accidents that had occurred and suggestions for developing four-wheelers. One hundred three answers (response rate 56%) were received. The respondents reported minor injuries (15%) and dangerous situations: the four-wheeler had fallen over (35%) and the driver had fallen off the four-wheeler (20%). The accidents and dangerous situations were concentrated to occupational users who drove a lot in poor terrain. Four-wheeler driving was estimated to be more dangerous than snowmobile driving. According to the answers the most efficient measures to improve safety would be the use of a safety helmet and high boots when driving as well as the enforcement of an age limit for the driver. The technical properties of the four wheelers could also be developed e.g. the leg room, foot board and protective roll bar. PMID- 1285825 TI - Ergonomic design of machinery for use in the cold. A review based on the literature and original research. AB - The main purpose of this paper is to identify some important problems associated with ergonomics of the human-machine-task-environment system under cold conditions. Practical examples of stress, strain and accident risks based on the literature and original research are given, and needs and possibilities for improving the ergonomic design of machinery are described. The awareness of designers to the demands set by cold conditions should be increased. Both the need for better operability and the need for better maintainability of machinery in the cold argue for the development of a new, systematic engineering design methodology. PMID- 1285826 TI - Work in the cold--an information and research program in occupational health. AB - Hundreds of thousands of employees work in the cold. The problems concerning cold are, to a great extent, well known. There are also good suggestions about how to deal with these problems. This project deals with: Cold stress, as an important risk factor for medical illness; the problems concerning clothing and equipment; how to change the snowmobile into a modern low risk piece of equipment: international standardization usable in the field; different approaches for information to reach and be used by the workers and their chiefs. PMID- 1285827 TI - Protective clothing against cold--performance standards as method for preventive measures. AB - Survival, function and comfort in the cold are dependent on a rational and cautious use of protective measures to reduce and control heat losses. International standards are now available for establishing a basis for the rational assessment of protection requirements and the subsequent selection of appropriate clothing. Protection requirements may be readily calculated by the IREQ-index (ISO/TR-11079), which specifies required resultant clothing insulation for given conditions. Performance of selected clothing ensemble can be tested by measuring the insulation value on a moveable, thermal manikin according to prEN 342. Similarly, performance of protective gloves against cold may be tested with a heated hand model (prEN-511). It is important to emphasize that the outlined procedure should only be applied as a guide-line for action. Due to considerable individual variation in capacities, preference and demand, room must be available for behavioral adjustments, as well as clothing must be flexible enough to accommodate these adjustments. PMID- 1285828 TI - Purification and characterization of CeqI restriction endonuclease. AB - CeqI, a type II restriction endonuclease, an isoschizomer of EcoRV was purified to apparent homogeneity by a combination of salt precipitation, ion exchange, dye affinity and hydrophobic interaction chromatographies. The crude enzyme was present in the form of large aggregates that could be pelleted by high speed centrifugation. The enzyme was not associated with cellular membranes, though non ionic detergents lowered the apparent size of the aggregates. The purified enzyme also showed a tendency to form large molecular mass (66-600 kDa) complexes under physiological conditions, in the absence of cleavable DNA. The enzyme formed smaller complexes in the presence of DNA and non-ionic detergents and dissociated into subunits (and undergoes reversible loss of activity) in the presence of high concentrations of salts. According to SDS gel electrophoresis and sedimentation analysis the molecular mass of the monomer 32 +/- 2 kDa. The enzyme had a rather broad PH optimum, extending into the alkaline range and lost specificity and activity in buffers below pH 6. PMID- 1285829 TI - Modulating luminol-dependent chemiluminescence of neutrophils by flavones. AB - The effect of 14 flavones on luminol-dependent chemiluminescence of neutrophils was studied in vitro. Chemiluminescence was used in this study as an indicator for the production of a reactive oxygen species by neutrophils, stimulated by phorbol myristate acetate. While flavone-8-acetic acid, and most of the compounds tested, inhibited chemiluminescence, flavone and its 5-hydroxy-7-methoxy derivatives enhanced it by up to 150%. The most active inhibitors of photon emission were the glycosides. These results indicate that lipophilicity and some structural determinants modulate the chemiluminescent capacity of neutrophils. PMID- 1285830 TI - Acid DNase activities in peripheral, mononuclear blood cells: a possible parameter to detect proliferating cell populations. AB - After electrophoresis in DNA-containing polyacrylamide gels, two acid DNase activities can be detected in peripheral, mononuclear cells of the human blood. One of these acid DNase activities correlates with cell proliferation; its isoelectrical point is at pI 7.4. By means of this DNase activity, a quantity of less than 1% leukemic cells can be detected. The increased acid DNase activity can indicate the proliferation of malignant cell populations and possibly the proliferation of cell populations during immunological reactions. PMID- 1285831 TI - Disturbing GTP-binding protein function through microinjection into the visual cell of Limulus. AB - We have tested the action of three agents microinjected into the ventral nerve photoreceptor of Limulus on the electrical response to dim light. 1. A monoclonal antibody (mAb 4A) against the G alpha subunit of frog transducin reduces the size of the receptor current to 60%, suggesting an interaction with G alpha in the Limulus photoreceptor. 2. Injection of Clostridium botulinum ADP ribosyltransferase C3 reduces the size to 46%; latency is not affected. The results imply that small GTP-binding proteins play a functional role in photoreception of invertebrates. 3. Injection of GDP-beta-S reduces dose dependently the size of the receptor current to 15% and prolongs the latency to 200%, presumably by reducing number and rate of G-protein activations. PMID- 1285833 TI - The biology of wound healing. AB - Wound healing is a complex biological process. A thorough knowledge of normal wound healing is of utmost importance for the clinicians who are involved in the care of patients with open wounds. It is imperative for every clinician who is involved in wound care to know the process which prevents, minimizes and eliminates those factors which adversely affect wound healing. PMID- 1285832 TI - Two phases of ferricyanide reductase activity in Ehrlich cell plasma membranes. AB - Ehrlich cell plasma membrane vesicles have a ferricyanide reductase activity that shows two phases. These two phases were kinetically characterized. Evidence is presented for a differential effect of trypsin on both phases. PMID- 1285834 TI - Documentation of skin using photography. PMID- 1285835 TI - Case study: traumatic pressure sore of the left lateral malleolus. AB - JB, a 62 year old male, was facing potential amputation of his lower left leg following traumatic injury in the left malleolar area. Previous treatments over an approximate six week period had not improved the wound condition. A sodium chloride impregnated dressing, Mesalt Sterile Sodium Chloride Impregnated Dressing, was tried as a last resort prior to amputation of the lower leg. Three weeks of therapy with this dressing documented dramatic improvements in wound size, odor, amount of drainage, type of drainage, surrounding skin condition and appearance of the wound bed. The simplicity of the treatment regimen facilitated care of the wound by nursing home staff, home care personnel and JB's son. After 17 weeks of therapy, the wound was completely healed and amputation avoided. PMID- 1285836 TI - Hold that tube ... cost effectively! PMID- 1285837 TI - Reevaluate your practice regarding pain and infection control: a personal experience teaches valuable lessons. PMID- 1285838 TI - Contact dermatitis in leg ulcer patients. PMID- 1285839 TI - Structural studies on bio-active compounds. Part 21. Acid-promoted debenzylations in antitumour 2,4-diamino-5-[4-(N-alkylbenzylamino)-3-nitrophenyl]-6-ethylp yrimidines. AB - Methylbenzoprim and ethylbenzoprim undergo debenzylation in hydrochloric acid. Two reaction mechanisms are proposed to explain this reaction, both of which involve a neighbouring group participation by the nitro group ortho to the tertiary amine fragment. The physical stability of dihydrofolate reductase inhibitors in the benzoprim class may influence the choice of a clinical candidate. PMID- 1285840 TI - Crystal structure determination at 2.3 A of recombinant human dihydrofolate reductase ternary complex with NADPH and methotrexate-gamma-tetrazole. AB - The crystal structure of the methotrexate-gamma-tetrazole (MTXT)-NADPH ternary complex with recombinant human dihydrofolate reductase (DHFR) has been determined and refined to R = 15.9% for 7003 data from 10.0 to 2.3 A resolution for the R3 lattice. Interpretation of difference Fourier electron density maps revealed that the cofactor NADPH is bound in an extended conformation, and the closest contact between cofactor and inhibitor is 3.1 A, between N(5) of the MTXT pteridine ring and the nicotinamide C(4) which transfers a hydride during the enzyme-catalyzed reaction. As in other DHFR complexes, MTXT is interpreted as protonated at N(1) by Glu-30, and the 2-amino group is hydrogen bonded to a structurally conserved water which also interacts with Glu-30 and Thr-136. The 4-amino group of MTXT hydrogen bonds to the carbonyl of Ile-7 and the phenolic hydroxyl of Tyr-121, and the alpha-carboxylate forms a salt bridge with the conserved Arg-70. In this structure, the amide carbonyl forms two hydrogen bonds with Asn-64 and a water molecule, whereas the gamma-tetrazole ring does not interact directly with the enzyme. The largest changes in the secondary structure on formation of the ternary complex involve the fold of a flexible loop near residues 40-46, and to a lesser extent the helical region near residues 102-109 and the beta-sheet regions near residues 71-75 and 157-159. PMID- 1285841 TI - [Allergic asthma to latex, proven by a bronchial provocation test]. AB - The authors report the case of a female cook who develops contact urticaria associated with rhinitis and asthma-type dyspnea when using rubber gloves in the course of her work. Allergy to latex was confirmed by a PRICK-test with latex, the presence of specific IgE in the serum, and the onset of contact urticaria after putting on gloves. A latex glove was rinsed with 10 cc of distilled water and the resulting solution, used as a spray, brought on a bronchospasm in the first two minutes. This bronchial provocation test proves that latex can cause asthma-type dyspnea when work involves contact with the substance. The speed of onset and intensity of the respiratory symptoms observed show that such a provocation test must be carried out with extreme care in patients with a marked sensitivity to latex. The future lies in the possibility of easily standardizing the latex protein concentration in order to be able to administer progressive doses without any systemic risk. This case draws attention to the probably underestimated possibility of latex-induced asthma in all subjects who are brought into repeated contact with latex, whatever their profession. PMID- 1285842 TI - [Anaphylaxis caused by carboxymethylcellulose: report of 2 cases of shock from injectable corticoids]. AB - Two cases of anaphylactic shock are reported, occurring after intra-articular injections of corticosteroids, containing carboxymethylcellulose (CMC), benzylic acid, polysorbate 80, and merthiolate. Skin tests and leukocyte histamine release are positive to CMC and negative to the other substances including the corticosteroids: prednisolone acetate and cortivazol . No cross-reactivity with hydroxypropylcellulose was demonstrated. These tests lead to incriminate CMC in these patients. Anaphylaxis to CMC seems exceptional, though CMC is widely used in agro-alimentary and pharmaceutical industries, as well as hydroxypropylcellulose. In one case, the possibility of a sensitization by CMC as a food additive is discussed, insofar as the patient has a fixed eruption which has been suspected to be owed to intolerance to food additives. PMID- 1285843 TI - Autoimmune features in atherosclerotic ischemic cardiomyopathy. AB - An high frequency of antimitochondrial autoantibodies has been reported in subjects affected with primary cardiomyopathies and it has been hypothesized that they could be involved in the pathogenesis of these diseases. In order to find out whether such autoantibodies could on the contrary represent an epiphenomenon of myocardial cell damage, we searched for antimitochondrial (AMA), antinuclear (ANA) and antismooth-muscle (SMA) non-organ specific autoantibodies in a group of 50 subjects (47 females and 3 males), over 65 years of age, affected with ischemic cardiomyopathy (ICM) due to atherosclerosis, a condition resembling other cardiomyopathies as it concerns ultrastructural aspects of myocardial tissue. The frequency of the autoantibodies tested in our patients resulted quite similar to that occurring in our healthy elderly control subjects (AMA: 14% vs 5.7%; ANA: 28% vs 23%; SMA: 12% vs 11.4%) and in normal aged population. On the basis of our data, the myocardial cell damage "per se" does not seem to influence significatively the production of non-organ specific autoantibodies. PMID- 1285845 TI - [Inhalation therapies for asthma in children]. PMID- 1285844 TI - [Poor tolerance of exertion during sports and bronchial hyperreactivity]. AB - 135 sportsmen and women, 55 girls, 80 boys, aged from 7 to 30 years, from various sports, who complained of bad tolerance of exertion were examined with an exercise test and isocapnic spontaneous hyperventilation. 61, about 45%, during a hyperventilation test had a fall of V.E.M.S. greater than or equal to 20%, showing bronchial hyperreactivity. After three tests, this fall index was greater than or equal to 50%. 68% of the positive responses were seen in boys and 2/3 of the subjects with a positive response were atopics. No other argument could be maintained from the questioning or clinical history to predict the positive or negative character of the hyperventilation (age, sporting level, symptoms, previous asthma or asthmatic, allergy). H.S.V.I. of the chests of a sporting population that complains of exertion intolerance, therefore allows verification of an H.R.B. assessment of its severity and to follow evolution after treatment. PMID- 1285846 TI - Calorimetric study of thermal denaturation of type I human placenta collagen. AB - The thermal denaturations of type I human placenta collagen were studied in different aqueous solutions in the temperature range from 274 to 345 K by differential scanning calorimetry. The thermodynamic parameters of denaturational process were accurately. The average temperature of denaturation of the collagen Td is 47.1 degrees C, and the denaturational enthalpy delta Hd is 8.43 kJ per mole of residue in salt-free aqueous solution at pH 3.7. The linear relationship of delta Hd with Td has been obtained for the various collagens studied. The various factors concerning the stabilization of collagen structure of the Sigma collagen have been demonstrated. The dominant factors are hydrogen bonding and the participation of water molecules in the collagen structure. It is concluded from the thermodynamic evidence obtained that the water-carbonyl model is preferable to other models. By means of calculating the van't Hoff enthalpy of the collagen denaturation, the number and the size of cooperative blocks of the Sigma collagen have been evaluated. Its molecule contains five cooperative blocks, each having 600 residues or so. The type I human placenta collagen is a multi-domain protein. PMID- 1285847 TI - Crystallographic refinement of trichosanthin at 2.6A resolution. AB - The molecule model of trichosanthin has been rebuilt by using the electron density map improved by the solvent flatten and in accordance with the primary structure put forward by Collins. The crystallographic refinement of two trichosanthin molecules (3828 nonhydrogen atoms) in an asymmetric unit has been carried out by means of the restrain least-square procedure and diffraction data to a resolution of 2.6 A. The results are: an R factor 0.223 and the r.m.s. deviation of the bond length = 0.023 A. The new molecular model is in good agreement with the electron density map calculated with the coefficient 2Fo-Fc. PMID- 1285848 TI - Disulfide containing proteins denatured in 6 mol/L guanidinium chloride are not completely unfolded. AB - The unfolded states of serum albumin, lysozyme and ribonuclease denatured in GuHCl with their disulfide bridges intact or reduced and carboxyamidomethylated have been compared by their circular dichroism, second-derivative and difference spectra in the ultraviolet region. Results obtained indicate that although the secondary structures of denatured proteins with intact disulfides are largely destroyed, they still have considerable ordered conformation even in 6 mol/L guanidinium chloride as indicated by the differences in the extents of exposure of the aromatic residues compared to the denatured proteins without the native disulfide bonds. PMID- 1285849 TI - Study of the RNA splicing defect in the common Chinese beta-thalassemia gene, IVS II nt. 654 C-->T by using mRNA/PCR. AB - With direct sequencing of the amplified cDNA, we analysed the transcript and mRNA splicing defect in a common Chinese beta-thalassemia mutant (IVS-II nt. 654 C- >T). The result shows that this mutant gene would not only produce abnormally processed beta-globin mRNA, but also transcribes a small amount of normally spliced mRNA, hence leading to beta+ thalassemia. The method described herein provides a simple and sensitive approach to the studies of gene expression and molecular defects in genetic diseases at transcriptional level. PMID- 1285850 TI - Etiological implication of autoantibodies to zona pellucida in human female infertility. AB - PROBLEM: Autoantibodies to zona pellucida (ZP) have been implicated as a cause of infertility in woman by three lines of clinical and laboratory evidence. METHOD: First, positive anti-zona activities, as assessed by the passive hemagglutination reaction (PHAR) using bovine red blood cells sensitized with porcine zona antigen, were detected in 45 of 1,872 serum samples collected from infertile women, but in only three (two nonpregnant and one pregnant) of 592 serum samples from control subjects. Their incidence in 320 women with unexplained infertility (5.6%) was much higher than that in 1,552 women with infertility of known cause (1.7%, P < 0.01), which was comparable to the incidence observed in 193 age matched fertile nonpregnant and pregnant women (1.5%, P < 0.05). None of the serum samples from 292 age-matched adult men and 100 children of between 5 and 10 years old gave a positive PHAR. Second, follow-up study for a minimum of 2 years with treatment revealed that no pregnancy occurred in 11 infertile women with a consistently positive PHAR, and only three pregnancies in 19 infertile women with a fluctuating positive PHAR. Third, three of seven serum samples from women who gave a consistently positive PHAR produced strong immunofluorescence reactions on human ZP even after adsorption with porcine and human AB blood cells. Pre exposure of human ZP to the sera showing positive immunofluorescence, including that of one patient undergoing an in vitro fertilization program, greatly diminished the number of spermatozoa of normal quality that bound to and penetrated across human ZP. CONCLUSIONS: The observed high incidence of anti-zona activities and long-term resistancy to treatment in women with unexplained infertility may be closely correlated with inhibition of sperm-egg interaction by anti-zona autoantibodies produced in these women. PMID- 1285851 TI - Anti-sperm antibodies in the male: detection and clinical impact. PMID- 1285852 TI - Analysis of T-lymphocyte subsets after phytohemagglutinin stimulation in normal and type 1 diabetic mothers and their infants. AB - PROBLEM: Our aim was to investigate the immunological status of diabetic pregnancy, which is an overlap of diabetic immunity abnormalities and the immunological modifications normally occurring during pregnancy. METHOD: We studied lymphocyte subpopulations and lymphokine production, after 96 h of phytohemagglutinin (PHA) stimulation, from normal and Type I diabetic pregnant women at delivery time and from the respective cord blood. RESULTS: Peripheral blood mononuclear cells (PBMC) from both normal and Type I diabetic mothers showed an increase in CD8+ and a decrease in CD4+ cells compared to the respective cord blood mononuclear cells (CBMC). Moreover, Type I PBMC showed a lower number of "activated" CD3+ DR+ cells and a higher number of CD8+ CD25+ cells with respect to normal women, which may reflect the dysregulatory pattern due to the autoimmune condition. Type I CBMC showed a big increase in the number of CD4+ Leu8+ cells, a cell subpopulation characterized by inhibitory activity. Finally, as regards lymphokine release in culture supernatants, type I diabetes seemed to be associated with an over-production of IL1 and IL6, although the latter increase is less evident in CBMC cultures. CONCLUSIONS: The present study shows that diabetic pregnancy is associated with major alterations of cell mediated immunity leading to a state of immunodepression. Moreover, our study suggests that the maternal immunological status influences fetal immunity, as demonstrated by the increase in the number of regulatory cells and by the altered pattern of lymphokine production (IL1 and IL6) by lymphocytes derived from diabetic CBMC. The latter phenomenon perfectly mirrors maternal PBMC characteristics. PMID- 1285853 TI - Effect of labor on lymphocyte subsets in full-term neonates. AB - PROBLEM: To determine the effect of labor on lymphocyte subsets in full-term neonates. METHOD OF STUDY: Cord blood obtained at delivery from full-term neonates, six born vaginally and six born by elective Cesarean section, was analyzed for lymphocyte subsets. Monoclonal antibodies, immunofluorescence, and flow cytometry were utilized to determine the lymphocyte phenotype frequencies in these neonates. These frequencies were compared by mode of delivery and to adult peripheral blood reference ranges using a two-tailed Student's t-test, P < 0.05. RESULTS: A profile of significantly elevated T (CD2, CD3) and helper cells (CD4) and depressed Natural Killer cells (CD16, CD56) is characteristic of term Cesarean section neonates. Significantly depressed frequency of T cells (CD2, CD3) and helper T cells (CD4) and elevated Natural Killer cells (CD16, CD56) is characteristic of vaginally delivered neonates. CONCLUSIONS: The mode of delivery affects the lymphocyte subset frequencies in full-term neonates. PMID- 1285854 TI - Development and distribution of the white blood cells within various structures of the human menstrual corpus luteum examined using an image analysis system. AB - PROBLEM: Emerging evidences suggest that immunoendocrine interactions play definitive roles during development and regression of the human menstrual corpus luteum (hmCL). We have studied the distribution of immune cells within individual structures of hmCL during various stages of its development. METHOD: Immunoperoxidase-stained ultra-thin frozen sections were evaluated using light microscopy fitted with an image analysis system. RESULTS: The results suggest that monocytes/macrophages and MHC class II positive cells are the most prominent immune cells within the hmCL throughout its whole lifespan. Both cell types are concentrated within the trabeculae. In addition, MHC class II positive cells are abundant also within the granulosa-luteal layer. T helper/inductor (Th/i) and T cytotoxic/suppressor (Tc/s) cells were detected only in minor amounts within the thecal trabeculae of mature tissue. CONCLUSIONS: Possible links between the occurrence and functional roles of the immune cells studied are discussed. PMID- 1285855 TI - Identification of lymphocyte subsets in the human fallopian tube. AB - PROBLEM: Immunohistochemical investigations for the detection of lymphocyte subsets in the human oviduct have been performed. Knowledge about local immunity especially cell-mediated immunity, in the fallopian tube has been, up to now, limited. As an essential structure for the human reproduction process, the tubal mucous membrane is exposed to a variety of antigens. METHOD: A total number of 20 tubal biopsies obtained from fertile women during gynecological operations like tubal ligations or hysterectomy were examined by the immunoperoxidase technique. Seven specimens were obtained during the proliferative phase, ten during the secretory phase and three during a caesarean section with tubal ligations. RESULTS: It could be established that the presence of lymphocytes in the oviductal mucous membrane is physiological. These cells can be identified by their typical immunohistochemical patterns. There were no significant differences of the type and number of lymphocytes in the mucosa within the phases of menstrual cycle. The dominant cell types in the tubal mucosa were the CD3+ and CD8+ lymphocytes. CONCLUSIONS: It can be suggested that the lymphocytes in the tubal mucosa may involved in the process of immune tolerance, which could realize the transport of sperms and blastocysts through the oviduct under normal conditions without activation of local immune mechanisms. The lymphoid tissue of the oviduct is a specialized form of mucosal-associated lymphoid tissue (MALT). PMID- 1285856 TI - The leukocytic reaction of the human uterine cervix. AB - PROBLEM: Sperm interaction with the immune system of the human cervix is poorly understood. METHOD: The leukocytic response of the human cervix to sperm was examined in a closely monitored patient population (N = 10), using monoclonal antibody cell identification techniques. Baseline data were collected from both cervical mucus and smears sampled before treatment by donor insemination. Donor insemination was timed to coincide with ovulation by monitoring plasma LH concentrations twice daily. Following insemination the numbers of leukocytes were recorded in cervical mucus and smear samples taken over a 24-h period relative to the time of treatment. Controls treated with "pure sperm," seminal plasma, cryopreservative, and cervical smearing alone were also included in the study. RESULTS: Only those women treated with sperm cells exhibited substantial elevations in leukocyte numbers following inseminations. Additionally, serial cervical smearing induced an inflammatory response of the cervix. In all the women, the neutrophil was the predominant leukocyte of the cervix both during the baseline and treatment periods (median values ranged from 77 to 86%). Macrophages, T-helper lymphocytes, and T-suppressor lymphocytes were also detected, but only in low numbers (2-10.6%). Two patients and one control ("pure sperm") became pregnant during their study cycle. CONCLUSIONS: We conclude that the leukocytic reaction is a physiological response of the cervix to sperm, the function of which remains to be established. PMID- 1285857 TI - Quantitative and qualitative changes in the intraepithelial lymphocyte population in the uterus of nonpregnant and pregnant sheep. AB - PROBLEM: Previous studies have revealed the presence of a unique population of CD45R+ granulated cells in the sheep uterine epithelium. In the present study, dramatic changes in this cell population and in the nongranulated lymphocytes in the uterine and endometrial glandular epithelium of non-cycling, cycling, pregnant, and postparturient sheep are described. In noncycling and cycling sheep, the granules in the granulated intraepithelial cells were small. From days 55 to 134 of pregnancy, the granules in these cells were large, and there was a significant increase (P < 0.01) in the proportion of this cell population in the uterine epithelium but not in the endometrial glandular epithelium located in the deeper region of the stroma. The number of these cells declined dramatically (P < 0.01) from 2 to 15 days after parturition. Both the tissue distribution and the time of activation of these cells suggests they are different from the granulated lymphocytes described in placentae of mice and man. CONCLUSIONS: It is concluded that this unique population of granulated cells is derived from lymphocytes, and that these cells become metabolically active from mid- to late-pregnancy and may play a physiological role during pregnancy or birth. In contrast, the number of nongranulated intraepithelial lymphocytes were suppressed throughout pregnancy and they probably do not play a role in pregnancy. PMID- 1285858 TI - Proceedings of the International Conference on Rheumatic Diseases in Pregnancy. May 17-22, 1992, Jerusalem, Israel. PMID- 1285859 TI - Physiologic adaptations of pregnancy. AB - Normal pregnancy changes include physiologic anemia, leukocytosis, and thrombocytopenia. Cardiac rate and stroke volume increase, vascular resistance falls, and creatinine clearance markedly rises. Thyroid binding globulin and cortisol binding globulin both increase, as do complement proteins and fibrinogen, the latter resulting in a normally high erythrocyte sedimentation rate. Estrogen and progesterone rise dramatically. Low back pain, hip and sacroiliac complaints are common. The cytolytic activity of natural killer (NK) cells is decreased, as are adhesion and chemotaxis of phagocytic cells. Antibody responses are normal. CD4 cells proportionately decrease. A large number of circulating proteins suppression lymphocyte proliferation, and T-cell interleukin 2 (IL-2) production may be suppressed. In studies of pregnant patients, controls must include normal pregnant women. PMID- 1285860 TI - Cytokines considered critical in pregnancy. AB - Cytokines considered critical in pregnancy include interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma, granulocyte macrophage colony stimulating factor (GM-CSF), and colony stimulating factor (CSF 1). They affect blastocyst attachment, trophoblast outgrowth, implantation, proliferation of cells isolated from placentas, proliferation of trophoblast cell lines, and percent fetal resorption in spontaneously aborting mice. Cytokines also affect chorionic gonadotrophin and progesterone production by trophoblast. Cytokine effects vary with concentration, route of administration, and timing of secretion. PMID- 1285861 TI - Immune recognition at the maternal-fetal interface: overview. AB - Trophoblast antigens at the maternal-fetal interface that are capable of stimulating maternal immune responses have been studied. Candidates are blood group I and P, HLA, Fc gamma-receptors, TLX, and phospholipids. Antigens I and P on trophoblast have been implicated in pregnancy loss but incompatible i,p mothers are rare. HLA-G is expressed on cytotrophoblast; however, no evidence for HLA-G allotypy or maternal responses to these molecules exists, although HLA-G has been implicated in recruitment of suppressor T cells. Receptors for IgG (Fc gamma-RI, Fc gamma-RII and Fc gamma-III) are present on trophoblast but allotypy is limited to the NA1-NA2 antigen system associated with Fc gamma-RIII on neutrophils. Maternal Fc-gamma R blocking antibodies have been linked to pregnancy success. The TLX alloantigen system was described by using xenogeneic antisera. Idiotype-antiidiotype regulated maternal responses to TLX are proposed as necessary for successful pregnancy. Several putative TLX monoclonal antibodies (Mab) recognize a regulator of complement activation called MCP (membrane cofactor protein, or CD46). Mab to MCP do not exhibit allotypy. Syncytial and cytotrophoblastic membranes are rich sources of MCP. Preliminary data suggest that a conformational site induced by C3b (iC3) binding to MCP may be responsible for TLX allotypy. Certain pregnancy loss patients produce antiphospholipid antibodies (aPA). Some investigators believe that aPA recognize a plasma protein cofactor, beta 2 GPI and not phospholipid per se. We produced three Mab specific for beta 2 GPI, one of which fails to recognize beta 2 GPI bound to phospholipid [corrected].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285862 TI - Ontogeny of T lymphocyte function in the neonate. AB - T cell precursors are first detected in the thymus at eight weeks of gestation. By 15 to 20 weeks of gestation, T-cell precursors expressing alpha beta and gamma delta T-cell receptors are present in the thymus in numbers relatively similar to those found in postnatal life. However, recent data suggest that T-cell receptor diversity is more limited during fetal and neonatal life than in adults. Additionally, the functional capacity of T cells in the fetus and neonate is immature, in that neonatal T cells express a limited repertoire of lymphokines in response to activation. Specifically, the production of the lymphokines, interferon-gamma and interleukin-4, which participate in the maturation of cytotoxic cells, activation of macrophages, and the maturation and modulation of B cell function and isotype expression, is reduced more than tenfold compared to cells from adults. This appears to result primarily from the lack of memory T cells in the fetus and neonate, reflecting their antigenic naivete. The difference in lymphokine expression is due to diminished transcription of these genes in neonatal T cells in response to activation. Preliminary data indicate that differences in essential promoter elements regulating transcription of these lymphokine genes plays a role in their differential expression in T cells. PMID- 1285863 TI - The effects of sex hormones on the immune system in pregnancy. AB - The immune system is affected by sex steroids. Immunoglobulin synthesis, T-cell subsets, and a variety of cytokines are targets for sex steroids. Hormonal variations are found in patients with rheumatic diseases. These variations include the hydroxylation of estrone and the oxidation of testosterone, both of which are altered in rheumatic disease. These changes are magnified in the pregnant state. More estrogen metabolites of the C-16 variety can bind to cells (lymphocytes and erythrocytes) and his reaction is accelerated in pregnancy. The role of the catechol estrogens is discussed. These compounds may be important to some of the vasospastic symptoms seen during pregnancy in patients; moreover, oxidation of testosterone to weak androgens is found in women with systemic lupus erythematosus (SLE). Overall, interesting observations and conclusions will evolve from a better understanding of sex hormone metabolism and its effects on the immune system in pregnancy. PMID- 1285864 TI - Glucocorticoid therapy for rheumatic diseases: maternal, fetal, and breast feeding considerations. AB - Glucocorticoids form the mainstay of therapy for many rheumatic diseases, especially systemic lupus erythematosus (SLE). Prednisone is the drug of choice, because it has been well described during the pregnancy and is the primary drug for maintenance therapy or to induce a remission. Principles for prescribing glucocorticoids would apply during pregnancy, recognizing that many effects of rheumatic disease and long-term therapy are similar to physiologic changes of pregnancy. Particular attention should be placed on screening for pregnancy induced glucose intolerance, hypertension, and delayed fetal growth. Although animal studies suggest an increased risk of oral clefts associated with glucocorticoids, several human studies have failed to demonstrate teratogenic or toxic effects. Nevertheless, rare cases of transient fetal adrenal suppression have been reported, so all infants should be monitored in the nursery. Breast feeding is safe, with clinically insignificant amounts of the drug being concentrated in breast milk. PMID- 1285865 TI - NSAIDs: maternal and fetal considerations. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) gained popularity in the late 1970s. Inhibition of prostaglandin synthesis with indomethacin has been reported to be effective for prevention of labor and for treatment for symptomatic polyhydramnios. Concern about its possible constrictive effect on the fetal ductus arteriosus has limited its use in pregnancy. Maternal indomethacin therapy has also been associated with reduction in urine production in the fetus and with oligohydramnios. Obstetricians have discouraged pregnant women from taking analgesic doses of aspirin, mainly because of the availability of paracetamol (acetaminophen), which causes less gastric irritation, but also because of fear of maternal and fetal hemorrhage and of possible premature closure of the ductus. These fears largely derive from studies on patients taking large doses and from extrapolation from other NSAIDs. The likelihood that treatment with 60-75 mg/day of aspirin markedly reduces the incidence of preeclampsia and fetal intrauterine growth retardation makes it important to reexamine its use. This review describes the pharmacology and pharmacokinetics of aspirin with particular reference to pregnancy and considers teratogenesis, prolongation of pregnancy and labor, maternal bleeding, fetal and neonatal bleeding, possible effects on the ductus arteriosus and pulmonary circulation, and possible nonspecific effects on intelligence and breast feeding and acute toxicity in the neonate. PMID- 1285866 TI - Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. AB - Active rheumatic disease may necessitate the treatment of pregnant and lactating patients with disease modifying (DMARD) or immunosuppressive drugs. This review summarizes data from the literature, and attempts to give some recommendations. Possible teratogenic effects of gold, penicillamine, and chloroquine are still disputed. As long as the issue is not settled, it seems prudent to stop using these agents as soon as pregnancy is diagnosed. Hydroxychloroquine has been used by some rheumatologists for treating pregnant patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) without malformations detected in the neonates. Sulphasalazine does not increase the rate of congenital abnormalities. Selected case reports have not shown any teratogenicity of cyclosporine A so far. However, the drug may cause fetal retardation. The use of standard doses of azathioprine does not increase the risk of congenital anomalies. By contrast, the antitumor agents cyclophosphamide, chlorambucil, and methotrexate are possibly teratogenic when given during early pregnancy, but may be less harmful in late pregnancy. Data on the excretion of DMARD and the cytostatic drugs are sparse. Because of insufficient data, breast feeding is not recommended in patients on antimalarials, penicillamine, cyclosporine A, and cytostatic drugs. Intramuscular gold and sulphasalazine seem to impose no major risk on the nursing infant. PMID- 1285868 TI - The effect of cyclophosphamide pulses on fertility in patients with lupus nephritis. AB - The effect of cyclophosphamide pulse therapy given in relatively small doses (10 mg/kg per pulse) in 17 females with lupus nephritis has been studied. Four females developed menopause; in one transient amenorrhea occurred. No changes in menstrual cycle were noted in the other 11 females, four of whom subsequently delivered five normal babies. These data suggest the relative safety of small doses of cyclophosphamide pulse therapy on gonadal function in females under age 40 years. PMID- 1285867 TI - The use of low dose aspirin in pregnancy. AB - Pregnancy-induced hypertension (PIH) in general and preeclampsia in particular are major causes of maternal and perinatal morbidity. Data from our studies and from a number of prospective controlled trials have suggested that aspirin in doses of 60-150 md/day during the second and third trimester reduces the risk of PIH and improves maternal and neonatal outcomes. The number of patients enrolled in these studies is relatively small. However, meta-analysis of existing trials suggests that low dose aspirin reduces the risk of PIH and severe low birth weight. Although no maternal or neonatal adverse effects associated with aspirin were observed, the use of aspirin in the third trimester has been reported to cause hemostatic abnormalities in both mother and neonate. Other complications associated with prostaglandin synthetase inhibitors include premature closure of the ductus and neonatal primary pulmonary hypertension. The use of aspirin in the first trimester is not associated with increased risk of structural malformations. On the basis of these findings and pending the results of ongoing large-scale randomized multicenter trials, we suggest that daily low dose aspirin (1 to 2 mg/kg/day) be recommended only for select women at high risk for developing PIH and its associated complications. PMID- 1285869 TI - Condition specific antepartum testing: systemic lupus erythematosus and associated serologic abnormalities. AB - Antepartum fetal surveillance is well established in the optimal management of any pregnancy complicated by maternal systemic lupus erythematosus and/or its associated serologic abnormalities. Our experience in antepartum surveillance of the "lupus pregnancy" from 1980 to 1988 is reviewed. An overall perinatal mortality rate of 6.06% compares favorably to the total intrauterine death rate range usually reported for this disease. PMID- 1285870 TI - Fetal echocardiography in the assessment of lupus pregnancies. AB - Fetal echocardiography is the most sensitive tool in detecting the earliest possible changes of the cardiovascular system related to maternal lupus. The institution of aggressive therapy at that time may still be able to reverse the process before permanent fetal cardiac injury occurs. Experience with this technique is described. PMID- 1285871 TI - Umbilical and uterine artery flow velocity waveforms in pregnant women with systemic lupus erythematosus treated with aspirin and glucocorticosteroids. AB - Pregnancy in systemic lupus erythematosus (SLE) is at high risk to the mother and fetus. Impaired utero-placental perfusion may increase fetal loss and intrauterine growth retardation. We assessed the changes in impedance to blood flow in the umbilical and uterine arteries in five patients with SLE treated with low dose aspirin and corticosteroids, using Doppler ultrasound longitudinally throughout pregnancy. Blood flow velocity waveforms of the umbilical and uterine arteries were studied by transabdominal and transvaginal Doppler ultrasound, respectively. Resistance index (RI) was measured every two to four weeks from week 10 to term, and the values obtained were compared to those of normal pregnancies. All five patients delivered uneventfully. One neonate was delivered at 36 weeks (2550 g) and one neonate was growth retarded (1900 g at 38 weeks). Three women delivered at 39 weeks (3585 g, 2850 g, and 2800 g). Most umbilical artery RI values obtained throughout pregnancy were above the 95th percentile of normal pregnancies. The highest values of RI of the umbilical artery were assessed in the case of fetal growth retardation. However, most measurements of RI of the uterine artery were under the 95th percentile of normal. The improved pregnancy outcome in patients with SLE treated with aspirin and corticosteroids seems to correlate with their normal uterine artery flow velocity wave forms. PMID- 1285872 TI - Early Doppler studies in lupus pregnancy. AB - The management of 56 pregnancies in 54 patients is presented, 52 with systemic lupus erythematosus and two patients with primary antiphospholipid syndrome. All underwent serial Doppler blood flow studies of the umbilical and uterine arteries from 14 weeks of gestation. Drug therapy was directed at disease activity and the fetus and mother monitored intensively to identify optimum time for delivery. End diastolic blood flow (EDF) studies were compared with anticardiolipin antibodies (aCL) and the lupus anticoagulant (LAC) to predict outcome of pregnancy in terms of mortality, Caesarian delivery, hypertension, and gestation. The absence of end diastolic blood flow predicted Caesarian delivery more accurately. The presence of EDF and the absence of aCL was consistent with a normotensive pregnancy. The presence of LAC was the best of the three in predicting fetal demise. PMID- 1285873 TI - Vascular events in placentae and organ allografts. AB - This investigation explores the transplantation analogy of placentae with allografted human organs. Biopsies of cardiac and renal allografts and placentae were studied immunocytochemically with antibodies to components of the immunological, coagulational, anticoagulational, and fibrinolytic systems. Cellular rejection of cardiac and renal allografts was identified by infiltrating lymphocytes and macrophages. This was accompanied by vascular damage characterized by loss of endothelial anticoagulant pathways, vascular deposits of fibrin, and depletion of arterial tissue plasminogen activator (tPA). Failing allografts, including placentae from abnormal pregnancies, demonstrated coagulation/fibrinolytic changes consistent with vascular rejection, regardless of the presence of cellular infiltrates. An IgM autoantibody to allogeneic endothelium was associated with vascular protection. Its presence in cardiac and renal transplant biopsies was associated with an absence of fibrin deposits, and its absence was associated with vascular damage. Atherosclerosis commonly was identified in allograft biopsies (including placentae from abnormal pregnancies). These changes were shown in serial biopsies of transplanted hearts to be preceded by or associated with diminished IgM autoantibody, impaired endothelial anticoagulant pathways, vascular fibrin deposits, and depleted arterial reactivity for tPA. These results indicate the transplantation analogy of pregnancy should be viewed more specifically as vascular smooth muscle cell and endothelial responses to as yet unidentified microenvironmental stimuli. PMID- 1285874 TI - Overview of lupus pregnancies. AB - Pregnancy in patients with systemic lupus erythematosus (SLE) requires consideration of 5 major issues: (1) What is the risk to the mother? (2) What is the risk to the fetus? (3) What is the effect and treatment of antiphospholipid antibody? (4) What is the risk of neonatal lupus? (5) Stability of the family unit, particularly in the events of maternal disability or death, should be discussed by all parties when a pregnancy is planned. Consistency of measurement criteria, standardized treatment protocols, and long-term follow-ups are needed in the future. PMID- 1285875 TI - Activation of the complement pathway: comparison of normal pregnancy, preeclampsia, and systemic lupus erythematosus during pregnancy. AB - To evaluate a flare of systemic lupus erythematosus (SLE) during pregnancy and to differentiate it from diseases of pregnancy, serological parameters are often utilized. However, there are conflicting reports regarding the merit of conventional measurements of complement and activation products. While in normal pregnancy the levels of serum C3, C4, and CH50 gradually rise, a decline in these levels occurs during the course of pregnancy in selected SLE patients. There is controversy regarding whether such falls represent decreases in the overall synthesis of complement or activation, the former theory being supported by a report of normal levels of the C1s-C1 inhibitor complex. During normal pregnancies, increases of complement split products, such as plasma C3a, may occur, and these correlate positively with elevations of C3. In pregnancies complicated by lupus, increases of C3a are often accompanied by a decline in total C3 and CH50. In a minority of non-SLE patients, preeclampsia has been associated with elevations of a variety of complement split products. Ba, C3a, C4d, SC5b-9, indicating activation of both the classical and alternative pathways. The CH50 levels tend to remain normal in these patients. In contrast, elevations of complement split products frequently accompany disease flares in patients with SLE. A high ratio of CH50/Ba may differentiate patients with preeclampsia from those with active SLE. A decline in conventional measures of C3, C4, or CH50 which is accompanied by elevations of complement split products appears to differentiate a lupus flare from non-SLE diseases of pregnancy. PMID- 1285876 TI - A study of 100 high risk lupus pregnancies. AB - Certain subgroups of lupus patients and those with circulating antiphospholipid antibodies (aPL) in particular, suffer a high rate of fetal loss. Over the past 4 years, we have prospectively studied 100 pregnancies in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome. In addition to conventional methods of monitoring SLE and fetal development, we have also used Doppler flow assessment of placental perfusion from the 14th wk of pregnancy onward. Patients with the antiphospholipid syndrome and previous history of thrombotic events were treated with daily heparin (10,000 IU) and low-dose aspirin (75 mg). Those without a history of thrombosis were treated with low-dose prednisolone, azathioprine, or hydroxychloroquine. Pregnancy loss was reduced from 81.3% in 101 previous pregnancies to 36.8% in 100 pregnancies managed by us. None of the patients who received hydroxychloroquine throughout the pregnancy presented fetal malformations. Careful management and close monitoring of the lupus pregnancy has substantially improved fetal outcome. PMID- 1285878 TI - The effect of systemic lupus erythematosus on pregnancy and pregnancy outcome. AB - This review provides an analysis of reports published since 1980 on the effect of systemic lupus erythematosus (SLE) on pregnancy and pregnancy outcome. The question whether pregnancy increases clinical flares and the severity of flares in patients with SLE during pregnancy has not been resolved because of difficulty in defining exacerbations of SLE and of preeclampsia. An analysis of major detailed reports indicates that maternal complications are reduced in patients who are in clinical remission prior to the onset of pregnancy compared with women with persistent disease activity. Complications are observed in 30%-50% of patients with inactive disease at onset of gestation. After exclusion of spontaneous abortions during the first trimester, fetal survival was 85%-90% in most reported case series. The best outcomes were reported in patients with inactive disease at onset of pregnancy. It seems likely that some maternal complications and fetal wastage in this population are related to anticardiolipin antibodies. PMID- 1285877 TI - Previous pregnancy outcome is an important determinant of subsequent pregnancy outcome in women with systemic lupus erythematosus. AB - Women with systemic lupus erythematosus (SLE) have increased adverse pregnancy outcomes. The reasons for these problems include maternal disease, clinical or serologic activity, medication use, and residual organ impairment from prior disease flares. In retrospective studies, pregnancy data are often treated cross sectionally, with births rather than mothers as the unit of analysis. Multiple pregnancies from the same mother may be highly correlated with each other. In an unmatched retrospective study, the first two pregnancy outcomes in lupus patients with anticardiolipin antibody (anti-CL IgG or IgM isotype) (cases N = 47) and without anticardiolipin antibody (controls, N = 125) were assessed according to birth order. A good outcome was defined as a full-term (> 38 weeks) live birth without neonatal complications. All other pregnancy outcomes were considered adverse outcomes. Therapeutic abortions and ectopic or molar pregnancies were excluded. Both cases and controls with an adverse outcome in their first pregnancy had at least a 50% chance of another adverse outcome in their second pregnancy. Cases with a late miscarriage (fetal loss at 14 to 20 weeks' gestation) in their first pregnancy had the highest risk, 80%, of an adverse outcome in their second pregnancy. Both previous pregnancy loss and anti-CL antibody status should be considered in the analysis of pregnancy outcomes in women with SLE. PMID- 1285879 TI - Pregnancy course and complications in patients with systemic lupus erythematosus. AB - Among 165 patients with systemic lupus erythematosus (SLE), we observed 21 pregnancies in 19 patients since 1987. The mean duration of disease at the time of pregnancy was 4.5 +/- 3 years. All but three patients required immunosuppressive treatment before and during pregnancy. The effect of pregnancy on the course of SLE was studied. Severe disease exacerbations were rare and largely confined to patients with renal involvement. Most patients showed elevated titers of dsDNA antibodies during pregnancy but clinical activity of disease was usually mild. Complement C3 decrease appeared to be the most sensitive marker for pregnancy-related complications. The detection of antibodies to phospholipids was frequent during pregnancy in contrast to a low prevalence before and after pregnancy. Their presence could be associated with intrauterine growth retardation. Preterm delivery before the 37th week of pregnancy had to be performed in the majority of patients. None of the patients experienced abortion although three patients had to delivered in the 29th week of pregnancy because of increasing symptoms of pre-eclampsia. Two of these children died and the third child suffered from intracranial hemorrhage in the early postpartum period. Our data demonstrate that successful pregnancy outcome was related to a gestational age of more than 32 weeks, making careful monitoring and appropriate therapeutic management necessary. PMID- 1285880 TI - Antiphospholipid antibodies: method of detection. AB - Antiphospholipid antibody, measured by enzyme-linked immunosorbent assay (ELISA) or by radioimmunoassay, and the lupus anticoagulant represent similar but different tests. The ELISA is now well standardized. It is at least partly, and possibly primarily, dependent on the presence of a cofactor, beta 2-glycoprotein I. Tests for both antiphospholipid antibody by ELISA and lupus anticoagulant should be performed in patients suspected of having this syndrome. PMID- 1285881 TI - Antiphospholipid antibodies: proposed mechanisms of action. AB - Antiphospholipid antibodies (APA) are a family of immunoglobulins that react with anionic phospholipids, or anionic phospholipids-protein complexes. Recent evidence would support the latter definition. Lupus anticoagulants (LA) inhibit in vitro phospholipid dependent coagulation tests [e.g., activated partial thromboplastin time (APTT), prothrombin time (PT), and dilute Russell viper venom time (dRVVT)]. This inhibition appears to be specific for reagent phospholipids. The addition of freeze-thawed platelets or activated platelets will result in correction of the LA-induced abnormality. Anticardiolipin antibodies (ACA) are related to LA but appear to be distinct. ACA are detected by solid phase assays (ELISA, RIA) and require a plasma cofactor: beta 2 Glycoprotein-I (beta 2 GPI). ACA and LA activities can be separated in individual patient plasmas by affinity chromatography. In some instances they are of differing isotypes. Preliminary evaluation of beta 2 GPI in coagulation assays suggests it may function as a cofactor for LA activity. Recent work also suggests human prothrombin may represent a necessary cofactor for in vitro LA activity. Paradoxically, patients with LA/ACA may sustain thromboembolic events involving both venous and arterial sites. The prothrombotic properties of LA/ACA have not been satisfactorily characterized. A number of proposals have been reported, including inhibition of prostacyclin (PGI2) generation by endothelial cells, decreased activity of the protein C system, impaired fibrinolysis, and inhibition of beta 2GPI. Among these various hypotheses, down regulation of the protein C system appears most plausible. Also, LA/ACA may interfere with the phospholipase A2-phospholipid substrate complex involved in the generation of arachidonic acid from membrane phospholipids. PMID- 1285882 TI - Treatment of patients with antiphospholipid antibodies during pregnancy. AB - Most authors agree upon the causal association between antiphospholipid antibodies [lupus anticoagulant (LAC) and/or anticardiolipin antibodies] and adverse pregnancy outcome. Placental insufficiency, caused by thrombosis, infarction and maldevelopment, is thought to be the main cause of fetal loss in patients with LAC. Therapy given thus far to prevent fetal loss can be divided into (1) immunosuppression by corticosteroids, azathioprine, or intravenous gamma globulin (IVGG), (2) anti-aggregants to overcome imbalance of thromboxane/prostacycline production in patients with LAC, and (3) anticoagulants to neutralize the possible impairment of clotting inhibitor systems. Different therapeutic success rates have been reported by various authors who used the same combination of therapy. We report the results of different therapy regimens in 154 pregnancies in 31 women with LAC. These patients suffered from SLE with LAC or from APLA syndrome and experienced either recurrent miscarriages or thromboembolic phenomena in the past. With no therapy there were seven (6.8%) live births and 95 (93.2%) failures. Various combinations of corticosteroids, anti-aggregants and anticoagulants were used for treatment. Of 52 treated pregnancies, 27 (51.9%) were successful. Sixteen (69.1%) of 23 pregnancies treated by all three modalities ended in live births. Four of these successful pregnancies occurred after failure of treatment by prednisone and anti-aggregants only. In order to minimize osteoporosis caused by the combination of steroids and heparin, we have used warfarin in the second trimester and have lately substituted low molecular weight heparin for heparin. In the absence of a therapeutic schedule predicated on a large prospective study, therapy during pregnancy in patients having LAC should be individualized according to their obstetric and medical history.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285883 TI - Induction of experimental primary and secondary antiphospholipid syndromes in naive mice. AB - In the current series of experimental studies we show that anticardiolipin antibodies (ACA) are pathogenic: Infusion of serum ACA to the tail vein of naive mice induces experimental antiphospholipid syndrome (APLS) characterized by thrombocytopenia, prolonged aPTT, and recurrent fetal resorptions. Similar experimental APLS is induced by active immunization with serum as well as with natural human monoclonal ACA. APLS is also associated with low fecundity rate. The experimental APLS models were employed to demonstrate the efficacy of aspirin, low molecular heparin, and interleukin-3 preventing recurrent fetal loss. In another experiment, immunization with human monoclonal anti-DNA antibody was followed by the induction of APLS secondary to experimental systemic lupus erythematosus (SLE). In all studies, IgGs were found to be more pathogenic than IgMs ACA. These studies confirm the autoimmune nature of APLS. PMID- 1285884 TI - Pregnancy and rheumatoid arthritis: an overview. AB - The literature concerning the relationship of rheumatoid arthritis (RA) to pregnancy is reviewed. The amelioration of RA during pregnancy is a complex process. No specific factor that causes amelioration and is amenable to therapeutic intervention has been identified. Either RA is associated with lower fertility/fecundity, or pregnancy induces a protective effect against the development of the disease. The biological mechanism of these findings is not established. PMID- 1285885 TI - Remission of rheumatoid arthritis during pregnancy and maternal-fetal class II alloantigen disparity. AB - Rheumatoid arthritis (RA) is an autoimmune disorder known to be associated with specific class II genes. Although it has been known since 1938 that the majority of women with RA experience disease improvement or remission during pregnancy, the reasons remain unknown. Pregnancy represents an immunologic challenge and maternal immune recognition of the semi-allogeneic fetus occurs as part of normal pregnancy. We hypothesized that maternal immune response to fetal HLA antigens might be associated with the effect of pregnancy on arthritis activity. To test this hypothesis, we studied HLA antigens in mother-child pairs comparing maternal fetal HLA antigen sharing for pregnancies where arthritis improved with those where disease was active. No significant difference was observed in the two groups for class I HLA antigens. Fetal-maternal disparity for HLA-DR and HLA-DQ antigens was observed significantly more frequently in pregnancies with remission or improvement compared with those in which disease was active. These observations suggest that maternal immune response to fetal paternally-inherited class II HLA antigens may be important in RA remission observed during pregnancy. PMID- 1285886 TI - Parity status and the development of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is one of a number of autoimmune diseases with a marked female excess in incidence, particularly during the reproductive years. It is of interest to investigate whether reproductive factors are important in determining susceptibility to RA. However, difficulties in dating the pathological onset of the disease can make it difficult to distinguish between the reproductive influence history on disease and the influence of (subclinical) disease on reproduction. In women with RA compared to controls, there is no excess of being unmarried. Most but not all studies, show an increase in nulliparity, whereas parity rates in fertile RA women are unchanged. There is an increased rate of onset postpartum, particularly in the first three months after delivery. There is no unifying biological explanation for these epidemiological findings, and it is likely that the apparently obvious link between reproductive experience and pregnancy is complex. PMID- 1285888 TI - The effect of pregnancy on ankylosing spondylitis, psoriatic arthritis, and juvenile rheumatoid arthritis. AB - It has long been established that rheumatoid arthritis improves during pregnancy. The gestational course of other inflammatory arthritides like ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile rheumatoid arthritis (JRA) has been less well studied. The present review summarizes the results of our retrospective and prospective studies on the interaction between these diseases and pregnancy. The results showed clear differences for their gestational course. Patients with PsA improved or even remitted in 80% of the pregnancies, whereas 80% of the AS patients had unaltered or aggravated disease symptoms. The 20% of AS patients who markedly improved while pregnant all had AS with accompanying diseases like psoriasis, ulcerative arthritis, or small joint arthritis. Quiescent JRA was not reactivated by pregnancy, and active disease at conception ameliorated in about 60%. Fetal outcome was not adversely affected by AS, PsA, or JRA nor did there occur serious intercurrent diseases during pregnancy. In AS and PsA patients delivery was mainly uncomplicated. Sequelae of JRA were a frequent cause for cesarean section in JRA patients. A postpartum flare during the first 3 months after delivery occurred in about 90% of the AS pregnancies, 70% of the PsA pregnancies, and about 50% of the JRA pregnancies. PMID- 1285887 TI - Estrogens and rheumatoid arthritis. AB - Epidemiological and immunological evidence has suggested that female sex hormones may play a role in the etiology and course of autoimmune diseases such as rheumatoid arthritis (RA). In this review the present clinical data with regard to estrogens and RA are discussed, with emphasis on the possible preventive effect of oral contraceptives on the incidence of RA and on the possibility of using estrogens as adjuvant therapy in RA. It is concluded that oral contraceptives may mitigate or postpone the onset of RA slightly, but that estrogens are not able to alleviate the symptoms of RA. Presently there is no evidence to promote the use of estrogens in preventing or treating RA in females. PMID- 1285889 TI - Pregnancy and scleroderma. AB - Scleroderma is a rare disease with a marked female excess in incidence. The pattern of age of onset, together with the effects of the disease, are such that the majority of women with scleroderma experience pregnancy prior to diagnosis. There are three questions of interest: (1) Does pregnancy adversely affect the prognosis of scleroderma? Isolated case reports suggest that renal disease, and in particular hypertensive crises, are associated with pregnancy in the absence of any renal abnormality before pregnancy. However, such events are rare. (2) Does scleroderma adversely affect either fertility or the outcome of pregnancy? Women with established scleroderma, again in case series, have a high rate of spontaneous miscarriage which is not found consistently in epidemiological studies. Prematurity and low birth rates are more frequent problems. (3) Does reproductive history influence disease and particularly Raynaud's phenomenon may antedate diagnosis by many years and might influence reproductive outcome, in general reproductive outcome is similar to that seen after diagnosis, although fertility appears to be reduced. PMID- 1285890 TI - Mapping of the familial Mediterranean fever gene to chromosome 16. AB - Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever, synovitis, peritonitis, or pleurisy. Some patients eventually develop systemic amyloidosis. The biochemical cause of the disease is unknown. We have conducted a genome-wide search for the FMF locus using 125 different DNA markers and mapped the FMF gene to the short arm of chromosome 16. The study was performed on 35 Israeli families primarily of North African and Iraqi origin. For the five markers D16S82 (p41-1 Sacl), D16S80 (24-1 Taq1), D16S84 (pCMM65 Taq1), D16S83 (pEKMDA2-1 Rsal), and HBA (5'HVR Rsal) we obtained maximum lod scores of 2.72 (theta = 0.08), 10.34 (theta = 0.04), 9.66 (theta = 0.050, 9.35 (theta = 0.03), and 14.31 (theta = 0.08), respectively. Multipoint analysis with HBA and D16S84 defined as a fixed loci gave a maximum lod score of 19.86 centromeric to D16S84. Crossovers defined by these markers place the FMF gene in an area of approximately 5 cM between D16S80 and D16S84. Other genes mapped to this area (16p13.3) include phosphodiesterase IB (PDE1B), hydroxyacyl-glutathione hydrolase (HAGH), phosphoglycolate phosphatase (PGP), and the gene that causes adult polycystic kidney disease (PKD1). None of these genes bear an obvious pathophysiological relationship to FMF. Using additional markers from this region we hope to localize more precisely the FMF gene and to offer the possibility of prenatal diagnosis in selected cases. Our ultimate goal is to isolate and characterize the FMF gene. PMID- 1285891 TI - The effect of pregnancy on renal function in amyloidosis of familial Mediterranean fever. AB - The effect of pregnancy on kidney function was studied in 29 pregnancies of 17 patients with familial Mediterranean fever (FMF) and amyloidosis. Pregnancy associated deterioration of renal function occurred in seven patients who had advanced renal disease at conception, marked by serum creatinine > or = 1.5 mg/dl or urine protein > or = 2 g/24 h. This finding suggests that the severity of renal disease at conception may predict the fate of kidney function during pregnancy and puerperium. PMID- 1285892 TI - Colchicine treatment in conception and pregnancy: two hundred thirty-one pregnancies in patients with familial Mediterranean fever. AB - The effect of maternal use of colchicine on fetuses is unknown. The children of 116 women with Familial Mediterranean Fever (225 completed pregnancies) were studied. There was no unusual frequency of fetal abnormality among women taking colchicine before or during pregnancy. Colchicine treatment does not apparently harm mother or child. PMID- 1285893 TI - Diffuse infiltrative lymphocytosis syndrome in children and adults infected with HIV-1: a model of rheumatic illness caused by acquired viral infection. AB - Certain maternal/infant pairs, as well as other high-risk adults, develop a host response HIV-1 infection characterized by circulating and tissue infiltrative CD8 T-cell lymphocytosis, termed Diffuse Infiltrative Lymphocytosis Syndrome (DILS). DILS primarily occurs in the salivary glands, lungs, renal interstitium, and gastrointestinal tract. DILS differs from Sjogren's syndrome in the degree of salivary gland enlargement, high frequency of extraglandular manifestations, paucity of autoantibodies, and distinct immunogenetic associations. Salivary gland B-cell lymphoma is a complication common to both conditions. The circulating CD8 T cells in DILS have a memory phenotype. Egress into target tissues involves adhesion molecule receptor-ligand interactions, apparently in response to the local presence of HIV-1. Immunogenetic predisposition involves interaction between both MHC classes I and II loci. This disease appears to reflect a specific host response that leads to persistence of monocyte-tropic, rather than T-cell-tropic, HIV-1 strains, in an analogous fashion to Visna Maedi virus disease in sheep. The development of DILS in children appears to be regulated in a dominant fashion by maternally or paternally inherited MHC class II alleles in response to transplacentally or perinatally acquired maternal HIV-1 strains. PMID- 1285894 TI - Nocturnal low back pain in pregnancy: polysomnographic correlates. AB - Thirteen women in late stages of pregnancy underwent a polysomnographic study. Eight women (61%) complained of mild nocturnal back pain or back discomfort. Five women (39%) did not complain of nocturnal back pain. The two groups did not differ in total bed time, total sleep time, sleep latency, and wake after sleep onset (WASO). A significant decrease in rapid eye movement (REM) sleep and an increase in stage 2 were observed in the pain group. The same group had a statistically significant decrease in the basal O2 saturation level. The pain group also spent a longer time sleeping in the supine position. We hypothesize that a prolonged stay in the supine position leads to obstruction of the vena cava. In the presence of inadequate collateral circulation, increased pressure and venostasis in combination with a decrease in basal oxygen saturation may lead to hypoxemia, compromise the metabolic supply of the neural structures, and result in pain. It appears, therefore, that the vascular system plays an important role in the pathogenesis of pain. The role played by the disturbed sleep architecture in the production of pain remains to be established. It is possible that the changes observed in sleep architecture result from pain rather than contribute to pain production. PMID- 1285895 TI - Problem areas of the rheumatic mother. AB - The extent to which women with rheumatic diseases are disabled in caring for their children is unknown. Fifty-seven women with rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or systemic lupus erythematosus, all of whom had children under 6 years of age born during the disease, were interviewed. Patients with different diseases differed in their disabilities, but lifting, carrying, transporting, and bathing the child were difficult for most patients. Attention to these problem areas is necessary in the care of young mothers with rheumatic illness. PMID- 1285897 TI - Neonatal lupus syndromes. AB - Neonatal lupus is a model of passively acquired autoimmunity in that immune abnormalities in the mother lead to the production of antibodies that cross the placenta and injure the developing fetus. Congenital complete heart block (CCHB), a permanent manifestation of neonatal lupus, is detectable after 18 wk gestation. Transient manifestations include cutaneous, hepatic, and hematologic abnormalities that occur at variable frequency. To date, there is a universal association of CCHB with maternal antibodies to SSA/Ro-SSB/La ribonucleoproteins, detectable by high ratio monomer:crosslinker SDS-immunoblot. Intriguingly, cardiac disease and often other manifestations are not present in the mother, raising the hypothesis that there is differential expression and/or accessibility of SSA/Ro-SSB/La antigens in fetal vs. adult tissues. CCHB may be a final consequence of a more widespread inflammatory response in the heart, including the existence of an associated myocarditis. In contrast to the in utero onset of CCHB, skin lesions generally become apparent after birth. Ultraviolet exposure may be an initiating factor and exacerbate an existing rash. Several studies have documented the predominance of DR3 alleles in mothers of affected offspring, frequently associated with the extended haplotype A1,B8. Available evidence suggests that fetal genetic differences in the major histocompatibility complex (MHC) do not influence susceptibility. The recommended clinical approach includes obstetric and rheumatologic management of both the fetus identified with CCHB and the fetus with a normal heart beat but at high risk of developing CCHB. Fetal echocardiogram is essential in diagnosing and following disease and may suggest the presence of an associated myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285896 TI - Target antigens of the SSA/Ro and SSB/La system. AB - The SSA/Ro and SSB/La antigens are polypeptides which serve as autoantigens in systemic lupus erythematosus and Sjogren's syndrome. The SSA/Ro contains two major isoforms of 60 kD and 52 kD. The former is the main native antigen while the latter is a major autoantigen in its denatured form. The SSB/La is a single phosphorylated protein of 48 kD. Recently a new protein of 46 kD, termed calregulin, was suggested as an additional component of the SSA/Ro antigens. However, extensive investigations failed to confirm its relation to the SSA/Ro system. Based on molecular techniques and cDNA cloning of these antigens, it was demonstrated that the 60 kD protein is capable of binding RNA and DNA molecules, suggesting a regulatory role in transcription for this antigen. The 52 kD polypeptide contains multiple zinc finger motifs and its sequence is homologous to the mouse rptl protein, which is a T-cell regulating peptide. The SSB/La is associated with precursors of 5S RNA and tRNA, implying that it has a role in the synthesis and maturation of RNA polymerase III transcripts. The 60 kD and 52 kD SSA/Ro components may be associated within the cell. The SSA/Ro and SSB/La may also be in complex in some points of the cell cycle. PMID- 1285899 TI - Autoantibodies in normal and abnormal pregnancy. AB - Abnormal autoimmune function has been associated with reproductive failure for decades. In fact, all medical conditions historically associated with pregnancy loss (and on occasion infertility) are now recognized to have an autoimmune etiology. It is therefore quite surprising that only less than a decade ago a correlation between the presence of abnormal autoantibodies and pregnancy loss was reported for the first time. Since reproductive failure, similar to other abnormal autoimmune states, is not a monoclonal event, we have established that affected patients demonstrate polyclonal autoantibody abnormalities including a variety of nonorganospecific as well as organspecific autoantibody groupings. For example, patients with repeated pregnancy loss will exhibit abnormal levels of anti-phospholipid antibodies (PA). In normal pregnancy natural autoantibodies do not follow the standard immunoglobulin (Ig) pattern, characterized by a decrease in levels despite a probably mild increase in production, which is excessively compensated by the vasodilatation of pregnancy. PA, especially, demonstrate a mild increase during pregnancy, though levels only in the peripartal period may reach abnormally high titers (in comparison to nonpregnant controls). This dichotomy between total Ig and natural autoantibodies is interesting since it suggests that autoantibodies may be under distinct control. In fact, we have suggested that this observed elevation of autoantibodies may be the result of an antigenic stimulus by self-like antigen, represented by the maternal growth of the parasitic fetus. In abnormal pregnancies, especially those associated with maternal hypertension and fetal growth retardation (IUGR), autoantibody levels do reach highly abnormal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285898 TI - Neonatal lupus erythematosus in offspring of mothers with experimental systemic lupus erythematosus. AB - Neonatal lupus erythematosus (NLE) syndrome is a result of the transfer of autoantibodies produced by the mother, across the placenta, to the fetus. NLE is characterized by a transient dermatitis, a variety of systemic and hematological abnormalities, and isolated cases of congenital heart block. The latter has been reported to be due to the presence of autoantibodies specific to La (SS-B) and/or Ro (SS-A). As female mice with experimental SLE, induced by immunization with the monoclonal anti-DNA 16/6 Id, produce a variety of autoantibodies including anti Ro and anti-La antibodies, we examined the relevance of NLE in the murine system. Offspring of SLE-afflicted BALB/c mothers possessed antibody titers to the 16/6 Id, ssDNA, and nuclear extract, which gradually declined until reduced to normal levels by day 60 after delivery. Antibody titers in the sera of the mothers remained elevated throughout this period. Electrocardiograms were recorded from groups of neonates from mothers with experimental SLE. The results indicated that a high percentage of the offspring had defects in their conduction system including first, second, and third degree heart block; significant bradycardia; and wide QRS complex. Normal patterns were observed in offspring of healthy mothers. Experiments done with mice that were exposed to SLE-related autoantibodies early in their development indicated that offspring to mothers with experimental SLE were neither protected nor more susceptible to disease induction by the 16/6 Id. PMID- 1285900 TI - Immune reproductive failure: effect of nonspecific immunostimulation in mouse model. AB - There is much evidence that pregnancy loss may be immunologically mediated. Failure of the maternal immune system to actively support the pregnancy may be responsible for its demise. Potentiation of immune functions has been attempted in humans; however, the success of immunotherapy is still not clear. Thus immunotherapy experiments in mouse models are important. Nonspecific immuno stimulation with complete Freund adjuvant (CFA) was shown in our laboratory to reverse the tendency to fetal loss in the CBA/J X DBA/2J mouse combination. CFA elevates the non-T lymphocyte population, decreases T-cell secreted lymphokines, and enhances macrophage-secreted monokines. However, a relationship between these changes and a beneficial effect of CFA on reproductive performance has to be proved. Information obtained from nonspecific immunopotentiation in the CBA/J DBA/2J model may contribute the assessment of nonspecific immunotherapy in humans. PMID- 1285901 TI - Immune features in complete Freund adjuvant-treated CBA/J mouse model. AB - Immunostimulation with complete Freund adjuvant (CFA) reverses the tendency to fetal loss in the CBA/J x DBA/2J mouse. First attempts to understand the mechanisms underlying this effect were to evaluate phenotypic and functional changes in the lymphocytic cell population after immunopotentiation. We demonstrated that treatment with CFA leads to diminished responses of maternal splenocytes towards paternal alloantigens and this low response cannot be improved with exogenous interleukin-2. Lymphocytes derived from spleen, para aortic draining lymph nodes and placenta significantly suppress maternal response to paternal antigens. The effect of low fetal resorption rate is followed by marked elevation of asialo GM-1 and HNK-1-positive cells but not followed by any change of the L3T4 or Lyt-2-positive lymphocyte population in either the spleen or in draining lymph nodes. L3T4 and Lyt-2-positive cells have not been found in the placenta. An important feature was marked elevation of Mac-1-positive cells in the placentas of CFA-treated animals. The relevance of these findings to CFA induced fetal protection is still under investigation. PMID- 1285903 TI - Immunological factors in infertility. AB - Immune infertility can result from destruction of gametes by antisperm antibodies (ASA) or anti-ovary antibodies, by inhibition of sperm-zona pellucida binding by ASA, or by prevention of embryo cleavage and early development. Condoms, immunosuppressive therapy, sperm processing, and intrauterine insemination have been widely applied, but with controversial results. PMID- 1285902 TI - Immunotherapy of habitual abortion. AB - Many cases of habitual abortion have been assumed to be due to hyporesponsiveness to the spouse's antigens encountered in pregnancy. Immunization by paternal leukocytes has been used to potentiate the immune response and prevent further miscarriages. This treatment has been highly controversial in terms of efficacy, mode of action, and side effects. More recently immunoglobulin has been used as passive immunization for similar indications. In our experience immunotherapy is effective; 80% of patients have subsequent live births. The most significant results are seen in patients with five or more abortions, in whom 66% of subsequent pregnancies develop normally compared to 20% in a control group. We have used antipaternal complement-dependent antibody (APCA) production after immunization as a marker of immune response. APCA correlates with beneficial outcome in the next pregnancy. APCA may also be associated with cytokines, which may enhance embryonic and trophoblast development. Immunoglobulin may similarly provide the relevant antibodies or cytokines. At present a large scale meta analysis is being performed to confirm or refute the efficacy of this treatment. This meta-analysis may resolve the controversy. PMID- 1285905 TI - Activity of a NAAG-hydrolyzing enzyme in brain may affect seizure susceptibility in genetically epilepsy-prone rats. PMID- 1285904 TI - The ontogeny of hippocampal local circuits and focal epileptogenesis. AB - Our understanding of the pathophysiological mechanisms underlying the childhood epilepsies is rudimentary at this time. However, results of recent studies in animal models have lead to a number of important hypotheses concerning age dependent alterations in seizure susceptibility. In area CA3 of hippocampus it appears that during a critical period when this brain area is particularly prone to electrographic seizures, an overabundance of recurrent excitatory synapses may exist. At the same time the synapses themselves appear to be functionally different than their mature counterpart. Age-dependent differences in the properties of postsynaptic NMDA receptors seem to contribute to enhanced seizure susceptibility. In recent years significant progress has been made in unravelling the fundamental processes that underlie the formation of connections between developing neurons. Over-production of early-formed axon collaterals appears to be common-place in the CNS. Moreover, the selection of appropriate patterns of connectivity appear to be dependent in large part on the patterning of neurophysiologic activity. In this regard the NMDA receptor seems to play a pivotal role in synapse consolidation. Based on these observations and the central role recurrent excitation appears to play in hippocampal seizures, it seems entirely plausible that excessive abnormal neuronal discharging that occurs during seizures early in life could result in the consolidation of abnormal numbers of recurrent excitatory synapses. This miswiring of hippocampal networks might be responsible for the marked seizure susceptibility into adulthood and might even contribute to complex partial epilepsy in individuals with a history of childhood seizures. PMID- 1285907 TI - Perspectives on early brain development and the epilepsies. PMID- 1285906 TI - Cloning, sequence and chromosomal localization of MK6, a murine potassium channel gene. PMID- 1285908 TI - Chronic models of cortical epilepsy: experimental manipulations leading to long term reorganization of local neocortical circuitry. PMID- 1285909 TI - An overview and perspective on the potential relevance of neuronal growth to the development of epilepsy and epilepsy-related disturbances. PMID- 1285910 TI - Migration disturbances in epilepsy. PMID- 1285911 TI - Regional changes in immediate early gene expression following focally-evoked limbic motor seizures. PMID- 1285912 TI - NMDA receptor-dependent epileptogenesis in developing inferior colliculus. PMID- 1285913 TI - Granule cell disorganization in the dentate gyrus: possible alterations of neuronal migration in human temporal lobe epilepsy. PMID- 1285914 TI - Granule cell dispersion in relation to mossy fiber sprouting, hippocampal cell loss, silent period and seizure frequency in the pilocarpine model of epilepsy. PMID- 1285915 TI - The possible pathological importance of dysgenesis, heterotopia and other cellular displacements in the brain. PMID- 1285916 TI - Developmental differences in the neurobiology of epileptic brain damage. PMID- 1285917 TI - Transcription of class II MHC gene by interferon-gamma in FRTL-5 cells. AB - The intracellular mechanism by which interferon-gamma induces the expression of class II major histocompatibility complex (MHC) antigen in nonlymphoid cells is not clear. The effect of recombinant rat interferon-gamma (IFN-gamma), and cycloheximide on the expression of class II MHC gene was studied using the techniques of immunocytochemical staining and northern blot analysis. IFN-gamma induced de novo transcription of class II MHC gene and class II MHC antigen expression on the cell surface. Cycloheximide did not inhibit IFN-gamma-induced class II MHC antigen expression in a dose-dependent manner indicating translational blockade. These results suggest that IFN-gamma induces class II MHC antigen expression via de novo transcription of class II MHC gene leading to synthesis of new class II MHC molecule. PMID- 1285918 TI - Clinicopathologic and immunophenotypic study of non-Hodgkin's lymphoma in Korea. Lymphoreticular Study Group of the Korean Society of Pathologists. AB - This study sponsored by the Lymphoreticular Study Group of the Korean Society of Pathologists was carried out to provide nationwide data about the histopathologic immunophenotypic features of malignant lymphomas in Korea. Two hundred and ninety Non-Hodgkin's lymphoma (NHL) among 312 malignant lymphomas collected from three representative areas in Korea were histologically reclassified. Two hundred and fifty three cases were immunohistochemically studied. T-cell lymphoma comprised 35.2% of NHL in this study and showed a quite comparable incidence to that of Japan and China, but it was much higher than in Western countries. A very low prevalence rate of the follicular variety (4.0%) and a higher propensity of primary extranodal involvement (60%) are additional characteristics of NHL in Korea. The most common histologic subtype of B cell lymphoma was diffuse large cell type, whereas the most common subtype of T cell lymphoma was diffuse mixed small and large cell type. PMID- 1285920 TI - Nonoperative management of persistent sciatic artery aneurysm--a case report. AB - A patient with a sciatic artery aneurysm, which is so rare that only 31 cases have been reported in the literature to date, was treated successfully with transcatheter arterial embolization (TAE) alone. Potentially risky and difficult surgery was avoided. This was the first trial with a good result. TAE alone is simple, safe and effective method for the treatment of sciatic artery aneurysm either in incomplete type or in complete type with adequate collateralization. PMID- 1285919 TI - A clinicopathologic study on the diffuse malignant lymphoma--a morphologic and immunophenotypic analysis in 62 patients at Harbor-UCLA Medical Center. AB - In order to compare the prognoses of patients with diffuse malignant lymphomas on the basis of histology and immunophenotypes, we retrospectively studied 62 cases of diffuse lymphoma arising in lymph nodes. We also evaluated the reactivity patterns of monoclonal antibodies (MoAb) LN1, LN2 and LN3 to determine the criteria for making a differential diagnosis in B cell lymphomas. The immunologic phenotypes were determined by the avidin biotin peroxidase complex method, using frozen or paraffin fixed tissues. The majority (66.3%) were B cell with the remaining 20.9% being T cell and 12.9% were non-B, non-T cell lineage. Immunological heterogeneity was found especially in the mixed small and large cell and the immunoblastic lymphomas. There was no significant difference between B- and T-cell lymphomas with respect to survival and death (P > 0.05). Histologically 79% (49/62) of the lymphoma was large cell and 21% (13/62), small cell lymphoma. There was a difference in prognosis between low, intermediate and high-grade of lymphomas. However there were no significant differences among the subtypes of the diffuse aggressive lymphomas. Factors associated with poor prognosis were advanced stages (P < 0.025) and histology of the malignant lymphomas. MoAb LN1, LN2 and LN3 gave positive staining in 83.3%, 91.7% and 60% of B cell lymphomas, respectively. The most common phenotypic pattern in B cell lymphomas was LN1+, LN2+, LN3+/-, suggestive of follicular center cell origin. As a panel, phenotypic patterns of MoAb LN1, LN2 and LN3 may be useful in differentiation of follicular center cell lymphoma from others. PMID- 1285921 TI - Inflammatory bowel disease in children--clinical, endoscopic, radiologic and histopathologic investigation. AB - This paper reviews our five years' clinical experience (1987 to 1991) of 22 patients with inflammatory bowel disease (IBD). There were 12 patients with Crohn's disease and 10 patients with ulcerative colitis. The mean age at diagnosis was 8.7 years (2 to 14 years). Clinical impressions before referral were chronic diarrhea in 11, irritable bowel syndrome in 5, colon polyp in 4, lymphoma in 3, intestinal tuberculosis in 2, amoebic colitis in 2, ulcerative colitis in 2 children and other diseases. The mean interval from the onset of symptoms to the diagnosis of IBD was 18 months. Diagnosis of Crohn's disease was delayed for more than 13 months in 8 (67%), whereas that of ulcerative colitis was delayed for more than 13 months in 4 (40%). Diarrhea (50%), abdominal pain (36%) and rectal bleeding (36%) were the three most frequent presenting complaints of IBD. Moderately severe abdominal pain was a more common chief complaint in Crohn's disease (58%) than in ulcerative colitis (10%). Hematochezia (90% vs 17%) and moderately severe diarrhea (90% vs 75%) were more common gastrointestinal manifestations in ulcerative colitis than in Crohn's disease. The associated extraintestinal manifestations were oral ulcer in 7, arthralgia in 11 and arthritis in 4, skin lesions in 2, eye lesions in 2 and growth failure in 9 patients. Of 12 children with Crohn's disease, granuloma was found in 5, aphthous ulcerations in 8, cobble stone appearance in 8, skip area or asymmetric lesions in 6, transmural involvement in 7, and perianal fistula in 3. Among 10 children with ulcerative Colitis, there were crypt abscess in 8, granularity or friability in 10 and rectosigmoid ulcerations with purulent exudate in 8 children. The main sites of involvement in children with Crohn's disease were both the small and large bowels in 7 (58%), small bowel only in 2 (16%), and colon only in 3 (25%). Terminal ileum involvement was seen in 75% of Crohn's disease cases. The main sites of involvement in children with ulcerative colitis were total colon in 4 (40%), up to the splenic flexure in 2 (20%), rectosigmoid in 3 (30%) and rectum only in one (10%). Medical treatment including sulfasalazine, and systemic or topical steroid was administered initially in most patients. Seven of 12 patients with Crohn's disease and 2 of 10 patients with ulcerative colitis were operated on.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1285922 TI - Modification of adriamycin-induced cytotoxicity by recombinant human interferon gamma and/or verapamil in human stomach cancer cells. AB - Recombinant human-interferon-gamma (rH-IFN-gamma) and verapamil (VRP), either alone or in combination, were evaluated in MTT assay for their modification effects on adriamycin-induced cytotoxicity against MKN-45, human stomach adenocarcinoma cells. VRP as a single agent did not inhibit the survival of MKN 45 at doses of up to 5.0 micrograms/ml. The survival of MKN-45 was inhibited by rH-IFN-gamma dose-dependently and further inhibited by the addition of VRP. However, the maximum growth inhibition of MKN-45 in any combination treatment with rH-IFN-gamma and VRP was less than 50% except in the highest concentration combinations (% survival: 47.9% at 10(4) U/ml of rH-IFN-gamma and 3.0 micrograms/ml of VRP). Adriamycin caused a concentration-dependent cytotoxicity and its cytotoxicity was significantly enhanced by the addition of rH-IFN-gamma and further enhanced by the combined use of rH-IFN-gamma and VRP. The modification effects of rH-IFN-gamma and VRP on adriamycin-induced cytotoxicity were evaluated in terms of modification index (MI), demonstrating that rH-IFN gamma significantly increased in adriamycin-induced cytotoxicity and that the combined use of rH-IFN-gamma and VRP enhanced the adriamycin-induced cytotoxicity to a greater extent than did rH-IFN-gamma alone: MI values at 10(2) U/ml and 10(3) U/ml of rH-IFN-gamma were 1.7 and 3.1, respectively; those at 1.5 micrograms/ml and 3.0 micrograms/ml of VRP in the presence of 10(3) U/ml of rH IFN-gamma were 4.4 and 6.0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285923 TI - Nosocomial pneumonia in medico-surgical intensive care unit. AB - Cases of hospital acquired pneumonia occurring during the 1st 12 months of Medico Surgical ICU (Intensive care unit, MSICU) in operation were evaluated retrospectively to determine its incidence, common causative pathogens, outcome and radiological patterns with the new hospital setting providing a unique relatively aseptic environment. Among the 920 admitted patients, 73 episodes of nosocomial pneumonia on 63 patients were identified and the incidence rate was 7%. The most common pathogens were Pseudomonas. Staphylococcus, Serratia, and Enterobacter in the order of frequency of occurrence, and the gram-negative pathogens comprised 70%. Nosocomial pneumonia was more common after use of antibiotics due to such pathogens as Enterobacter, Acinetobacter, and Candida which caused poor outcome. Enterobacter had the greatest tendency to be related with poor outcome and Serratia the least. Overall mortality was 25%. Bronchopneumonia was the most common type of pneumonia caused by any pathogen except Acinetobacter which caused a mixed type of nosocomial pneumonia. PMID- 1285924 TI - MR imaging of the internal carotid artery in ischemic cerebrovascular disorders- clinical and angiographic correlation. AB - This study was intended to correlate the appearance of the cavernous segment of the carotid artery on MR images with the presence of significant stenosis or occlusion of the cervical carotid artery as seen on angiograms in 37 patients with cerebrovascular disorders who had brain MRI and arteriography. Three patients demonstrated an isointense signal within the carotid artery's cavernous segment, correlating with complete carotid occlusion as seen angiographically. Ten patients had variable signal intensity and/or luminal narrowing in the carotid siphon; seven of these findings correlated with angiographic evidence of carotid occlusion, while carotid branch occlusion was seen angiographically in the other three. The demonstration of normal signal void within a normal appearing cavernous segment of the internal carotid artery in the remaining 24 patients correlated with an absence of significant stenosis within the cervical segment in 21 patients. In the remaining three, significant disease of the internal carotid artery was found. Isointensity or luminal irregularity within the intracranial carotid artery can indicate complete occlusion or slow flow. The presence of normal flow void in the intracranial segment does not exclude significant abnormality of the cervical segment of the carotid artery. PMID- 1285925 TI - Pediatric gastric volvulus--experience with 7 cases. AB - Gastric volvulus, organoaxial or mesenterioaxial, is a rare condition in infancy and childhood. We experienced 7 cases of pediatric gastric volvulus, consisting of 3 cases of secondary gastric volvulus due to left diaphragmatic eventration or paraesophageal hernia and 4 cases of idiopathic gastric volvulus. Of 7 cases, five were organoaxial in type and two were mesenterioaxial. The main symptoms of secondary gastric volvulus were vomiting and respiratory difficulty whereas those of idiopathic gastric volvulus were abdominal distension and weight loss with or without failure to thrive. It may be suspected on plain abdominal radiographs and usually confirmed by upper gastrointestinal series. Upper gastrointestinal series in organaxial volvulus demonstrated characteristic findings such as reversal of the greater and lesser curvatures and two air-fluid levels. In mesenterioaxial volvulus, the stomach was rotated into inverted position with pyloroantral obstruction showing a beak appearance. The three patients with secondary volvulus underwent repair of associated defect with or without gastropexy and the 3 patients with idiopathic volvulus underwent anterior gastropexy or gastrostomy. In those with idiopathic gastric volvulus, there was no obvious cause such as laxity of the perigastric ligaments. The operative results were satisfactory except for the three patients with idiopathic gastric volvulus whose abdomen remained distended regardless of weight gain. PMID- 1285926 TI - 'Pauci-immune' rapidly progressive glomerulonephritis associated with systemic vasculitis. AB - 'Pauci-immune' glomerulonephritis has been recognized as an important cause of rapidly progressive glomerulonephritis. The paucity of immune deposits can be separated from the other two major immunohistologic variants of crescentic glomerulonephritis, ie, antiglomerular basement membrane (GBM) antibody-mediated and immune complex-mediated glomerulonephritis. Here we describe the case of a 42 year-old woman with pauci-immune' glomerulonephritis and vasculitis presenting as rapidly progressive renal failure with characteristic pathologic and immunohistologic findings. And in this case, despite oliguria and rapid deterioration of renal function, the renal function recovered partially and continued to be stabilized with a favourable response to hemodialysis and combined system immunosuppressive therapy. PMID- 1285927 TI - Primary non-Hodgkin's malignant lymphoma of the vulva--a case report. AB - A case of primary non-Hodgkin's malignant lymphoma of the vulva which occurred in a 68-year-old woman is presented. Non-Hodgkin's malignant lymphoma is infrequently involved in the female genital tract. Moreover, primary vulvar involvement of this tumor is very rare. To date only 6 cases have been reported in the literature. To our knowledge this is the first reported case of a non Hodgkin's malignant lymphoma of the vulva in Korea. PMID- 1285928 TI - Swimming headache followed by exertional and coital headaches. AB - Seven patients who developed a similar headache syndrome are described. They first developed severe, exploding headaches while swimming, and subsequently experienced less severe headaches during physical exertion. They also developed headaches during sexual activity, which were similar to the previous headaches brought on by swimming. Majority of them were women in their thirties or forties. These symptoms were gradually subsided with or without medication after several weeks or months. The possible pathogenesis of this headache syndrome is discussed. PMID- 1285929 TI - Microphthalmos with cyst--case presentation. AB - The author has experienced a case of microphthalmos with large orbital cyst in a 4 months old female, that was found at the time of birth. To facilitate fitting a cosmetic prosthesis, the microphthalmos with cyst was removed surgically. On serial section I could find an area of discontinuation of the sclera that was suspected to be the defective closure of the embryonic cleft. Some aberrant retinal tissue was found in the wall of the cyst, and markedly disorganized ocular tissue forming a tumor-like mass filled the microphthalmic eyeball. In view of these histopathologic findings I could draw the conclusion that developmental failure of the embryonic eyeball and consequential proliferation of the embryonic neuroepithelial cells occurred at an early developmental stage causing the formation of microphthalmos with cyst. PMID- 1285930 TI - Autoimmune oophoritis--a case report. AB - A case is described of an autoimmune oophoritis that was diagnosed unexpectedly after a hysterectomy and bilateral salpingo-oophorectomy had been performed on the suspicion of ovarian cysts. The patient was a 43-year-old multiparous woman who presented with vaginal bleeding and lower abdominal pain which she had had for one month. Grossly, the ovaries were enlarged and multicystic. The cysts measured up to 3.0 cm. The major histological change was a lymphoplasmacytic infiltrate in close relation to the theca interna of developing, cystic and atretic follicles, but sparing the primordial follicles. The infiltrate increased in density with the follicular maturation and culminated against the corpus luteum. With involution of the developing follicles, the inflammatory infiltrate subsided to some extent. The proportion of the plasma cells increased with the density of the infiltrates. Immunohistochemical study of the ovarian mononuclear cell infiltrate revealed a mixture of B- and T-lymphocytes. The plasma cells were polyclonal. These histological features of the present case are typical of autoimmune oophoritis although the presence of autoantibodies and hormonal level in the patient's serum were unknown. This case may be identified as in the early active stage of autoimmune oophoritis. PMID- 1285931 TI - Spinal epidural granulocytic sarcoma preceding acute myelogenous leukemia. AB - A rare case of spinal epidural granulocytic sarcoma (GS) preceding acute myelogenous leukemia is described. A 10-year-old boy presented with lower leg weakness. The initial diagnosis was a histiocytic lymphoma, and he was treated accordingly. No evidence of bone marrow involvement was found at that time. The correct diagnosis of epidural GS was made possible in retrospect by using immunoperoxidase staining for lysozyme fourteen months later when the patient showed the full-blown features of leukemia. This rare tumor should be considered in the differential diagnosis of an epidural mass with cord compression in patients with or even without acute leukemia, because early diagnosis followed by appropriate combined chemotherapy and radiation may obviate surgical intervention and eventually prevent leukemic transformation. PMID- 1285932 TI - Antibodies as molecular probes in neurobiology. Identification of chemically defined neurons and synapses in tissues and tissue cultures. AB - Immunocytochemical localization of 5-hydroxytryptamine (5-HT) in the nervous system and aggregate tissue cultures was performed employing an antibody to 6-OH 1,2,3,4-tetrahydro-beta-carboline. A number of immunochemical and biochemical tests with the antigen and the antibody and some procedural changes in the methodology applied for immunolocalization revealed the anti-5-HT-like affinity of the antibody, if applied in paraformaldehyde-fixed tissues. Studies in the hypothalamus, striatum, brainstem, spinal cord, and pineal gland show the complexities of the serotoninergic system. Ultrastructural immunocytochemistry with the preembedding technique reveals that 5-HT synapses are of the asymmetric type. The presynaptic element contains clear, round, small vesicles, with some large dense-core vesicles. The contacts are made with the somata and primary, secondary dendrites or with spines of non-5-HT neurons. Presynaptic dendrites are found in the n. raphe dorsalis, contacting non-5-HT dendrites. Double immunocytochemical methods demonstrated contacts of 5-HT fibers on enkephalin containing neurons of the spinal trigeminal nucleus and on somatostatin containing neurons of the medullary reticular formation. In vitro studies of cultured mesencephalic neurons were performed with the method of aggregating cultures. Such development of a miniature organized nerve tissue was followed up to 35 d in culture. Organization of the neuropil and synaptogenesis was studied using standard electron microscopy. The differentiation of neurons and astrocytes was studied using antibodies to 5-HT and GFAP. Serotonin immunoreactivity could be observed in neuronal bodies and processes at light microscope level as early as the fourth day of culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285934 TI - Trophic factor effects on cholinergic innervation in the cerebral cortex of the adult rat brain. AB - The cholinergic pathway ascending from the nucleus basalis magnocellularis (NBM) to the cortex has been implicated in several important higher brain functions such as learning and memory. Following infarction of the frontoparietal cortical area in the rat, a retrograde atrophy of cholinergic cell bodies and fiber networks occurs in the basalocortical cholinergic system. We have observed that neuronal atrophy in the NBM induced by this lesion can be prevented by intracerebroventricular administration of exogenous nerve growth factor (NGF) or the monosialoganglioside GM1. In addition, these agents can upregulate levels of cortical choline acetyltransferase (ChAT) activity in the remaining cortex adjacent to the lesion site. Furthermore, an enhancement in cortical high affinity 3H-choline uptake and a sustained in vivo release of cortical acetylcholine (ACh) after K+ stimulation are also observed after the application of neurotrophic agents. Moreover, these biochemical changes in the cortex are accompanied by an anatomical remodeling of cortical ChAT-immunoreactive fibers and their synaptic boutons. PMID- 1285933 TI - Comparative biochemical pharmacology of central nervous system dopamine D1 and D2 receptors. AB - The biochemical properties of central nervous system (CNS) dopamine (DA) D1 and D2 receptors were examined using the specific antagonists [3H]SCH23390 and [3H]raclopride, respectively. There is a different participation of sulfhydryl ( SH) and disulfide (-SS-) groups in the binding site and/or coupling to second messenger systems of D1 and D2 receptors. The ionic studies with [3H]SCH23390 showed slight agonist and antagonist affinity shifts for the D1 receptor. On the other hand, the D2 receptor is very sensitive to cations; even if lithium and sodium influence specific [3H]raclopride binding in a similar manner, there appear to be quantitative differences between these two ions that cannot be explained by surface charge mechanisms. The distribution of D1 and D2 receptors was heterogenous in both species, with the greatest densities in the neostriatum, where the highest concentrations of DA and metabolites were measured. Regions with low endogenous DA content (cerebral cortex and hippocampus) had lower densities of DA receptors. Furthermore, these binding sites were differentially localized within the various regions, and there were substantially more D1 than D2 receptors. The functional significance and heterogeneities in the distribution of D1 and D2 receptors can be related to dopaminergic innervation and turnover. PMID- 1285935 TI - Structural and functional crosstalk between acetylcholine receptor and its membrane environment. AB - Nicotinic acetylcholine receptor (AChR) is a transmembrane protein belonging to the superfamily of rapid, ligand-operated channels. Theoretical models based on thermodynamic criteria assign portions of the polypeptide chains to the lipid bilayer region. From an experimental point of view, however, the relationship between the two moieties remains largely unexplored. Current studies from our laboratory are aimed at defining the structural, dynamic, and functional relationship between membrane lipids and AChR. We are particularly interested in establishing the characteristics of and differences between the lipids in each leaflet of the bilayer and the belt or "annular" lipids immediately surrounding AChR and the bulk bilayer lipids. We are also interested in determining the possible implications of lipid modifications on AChR channel properties. Toward these ends, fluorescence and other spectroscopic techniques, together with biochemical analyses and patch-clamp studies, are currently being undertaken. Correlations can be established between structural aspects of phospholipid packing in the immediate perimeter of AChR and other properties of these annular lipids revealed by dynamic spectroscopic and molecular modeling techniques. Lipid compositional analyses of the clonal muscle cell line BC3H-1 and chemical modification studies have been carried out by incubation of intact cells in culture and of membrane patches excised therefrom with liposomes of different lipid composition. These studies have been combined with electrophysiological measurements using the patch-clamp technique, with the aim of determining the possible effects of lipids on the channel properties of muscle-type AChR. A variety of experimental conditions, involving polar head and fatty acyl chain substitution of phospholipids and cholesterol incorporation, are being assayed in the BC3H-1 cells. PMID- 1285936 TI - Comparative effects of nitrendipine and hydrochlorothiazide on calciotropic hormones and bone density in hypertensive patients. AB - The effects of the calcium antagonist nitrendipine and the diuretic hydrochlorothiazide on plasma calciotropic hormone concentrations and lumbar bone density were compared during the treatment of hypertension in a randomized, double-blind, 8 week parallel study, followed by a 52 week open label study. There were 32 subjects with stable essential hypertension (sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg without medication) without evidence of renal insufficiency or active heart disease. They were randomly assigned to receive either 10 mg nitrendipine twice daily or 50 mg hydrochlorothiazide daily. In order to reach and maintain target blood pressure (diastolic blood pressure < or = 95 mm Hg) during the open label period, the nitrendipine dose was titrated up to 30 mg twice daily, and additional antihypertensive drugs, of differing classes, were added as necessary. Blood samples were analyzed for concentrations of calcium, parathyroid hormone, and calcitonin, and lumbar bone density was determined by dual photon absorptiometry, at the baseline and at 24 and 52 weeks of antihypertensive drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285938 TI - In vivo and in vitro effects of isradipine on cytosolic Ca2+ concentration in erythrocytes from spontaneously hypertensive rats. AB - Cytosolic Ca2+ concentration ([Ca2+]i) was investigated in erythrocytes from spontaneously hypertensive rats (SHR) and their normotensive controls (WKY), after an acute treatment with the Ca2+ antagonist isradipine. Blood samples were obtained from conscious rats and [Ca2+]i measured with fura-2. The [Ca2+]i was higher in SHR than in WKY erythrocytes (P < .05). Isradipine administration had no effect on WKY [Ca2+]i, but reduced that of SHR to WKY levels after 1 h. In vitro, isradipine dose-dependently decreased [Ca2+]i only in SHR (P = .006). The reduction by isradipine of the elevated [Ca2+]i in SHR suggests the presence of a greater dihydropyridine-sensitive Ca2+ influx in the SHR erythrocyte. PMID- 1285937 TI - Comparison of ambulatory and clinic blood pressure and heart rate in older persons with isolated systolic hypertension. AB - We compared the blood pressure (BP) measurements obtained with a random-zero sphygmomanometer and an ambulatory BP monitor in older persons with isolated systolic hypertension at one site of the multicenter, randomized, double-blind clinical trial, the Systolic Hypertension in the Elderly Program (SHEP) randomized clinical trial. The subjects were community-dwelling elderly participants with isolated systolic hypertension enrolled in the SHEP study and already receiving stable doses of double-blind medication (n = 35 for active treatment group; n = 32 for placebo group). We measured seated (clinic) BP obtained with a random-zero sphygmomamanometer, pulse rate, and BP and heart rate measurements obtained with an ambulatory BP monitor (average 24 h, daytime, and nighttime BP and heart rate). Across treatment groups clinic and ambulatory systolic BPs were not significantly different, but the placebo group had higher ambulatory, but not clinic, diastolic BPs. Within each treatment group (active treatment and placebo) there were no significant differences between clinic and average 24 h, daytime, or nighttime ambulatory systolic BPs. There were also no significant differences between clinic diastolic BP and average 24 h, daytime, or nighttime ambulatory diastolic BPs in the active treatment group, but in the placebo group average 24 h diastolic BP obtained by the ambulatory monitor was 4.6 mm Hg higher than clinic diastolic BP (P = .001). The average 24 h heart rate was 6 to 7 beats/min higher as measured by the ambulatory monitor compared to clinic pulse (P < .01). In the placebo group of this study, average 24 h ambulatory diastolic BPs were consistently higher than clinic diastolic BPs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285939 TI - Decreased insulin-sensitive Ca2+ transport in cultured vascular smooth muscle cells from spontaneously hypertensive rats. AB - To investigate the role of insulin on Ca2+ regulation of vascular smooth muscle cells (VSMC) in hypertension, the effect of insulin on Ca2+ transport and intracellular free calcium concentration ([Ca2+]i) was measured in cultured VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake as well as [Ca2+]i in quiescent cultured VSMC. The stimulatory effects of insulin were completely inhibited by diltiazem, and partially by H-7, TMB-8, and 5-N,N(hexamethylene)amiloride (HMA), but not by W-7 or trifluoroperazine. Insulin-sensitive 45Ca uptake of SHR VSMC was significantly smaller than that of WKY VSMC. Insulin-sensitive increase in [Ca2+]i of SHR VSMC was also smaller than that of WKY VSMC. It is concluded that insulin increases 45Ca uptake, leading to an increase in [Ca2+]i, presumably through the voltage-dependent Ca2+ channel, intracellular Ca2+ release, or protein kinase C mediated mechanisms in cultured VSMC. A blunted response of insulin-sensitive Ca2+ uptake and [Ca2+]i in SHR VSMC suggests the differential regulation of Ca2+ transport in response to insulin in primary hypertension. PMID- 1285940 TI - Effect of amlodipine on mesangial cell proliferation and protein synthesis. AB - Mesangial cells in the glomerulus have several important physiological functions, as has been demonstrated by past research. Platelet derived growth factor, thrombin, endothelin, and angiotensin II have all been shown to affect mesangial cell growth and protein synthesis. First generation Ca channel blockers also have a definite effect on mesangial cell proliferation. We investigated whether the effects of a second generation Ca channel blocker, amlodipine, were similar. Amlodipine was found to inhibit hyperplasia and hypertrophy in mesangial cells. PMID- 1285941 TI - Leisure time physical activity and insulin resistance in young obese students with hypertension. AB - To investigate the hypothesis that insulin resistance plays a role in the etiology of hypertension and hyperlipidemia, we measured serum lipid levels, the fasting glucose/insulin ratio, and the insulin response to oral glucose (GTT) in a group of young obese subjects (n = 21) with hypertension and normal glucose tolerance and in normotensive subjects (n = 36) with normal glucose tolerance, matched for age and body mass index. Leisure time physical activity was evaluated by a questionnaire outlining three levels of physical activities during leisure time. Subjects with hypertension had higher fasting serum insulin (19 +/- 2 v 13 +/- 1 microU/mL, P < .01) and lower fasting glucose/insulin ratio (5.3 +/- 0.2 v 7.1 +/- 0.5 mg/dL/microU/mL, P < .01) than normotensive subjects. Subjects with hypertension had higher peak serum insulin and lower plasma glucose area/insulin area ratio in response to glucose (1.8 +/- 0.2 v 2.4 +/- 0.2 mg/dL/microU/mL, P < .05) than normotensive subjects. Serum total cholesterol, low-density cholesterol, and triglycerides were higher in the obese hypertensive subjects than in obese normotensive ones. Blood pressure correlated with either fasting serum insulin, fasting glucose/insulin ratio, or glucose area/insulin area ratio during GTT. The level of leisure time physical activities was lower in obese hypertensive subjects than in obese normotensive ones. There were significant correlations between the levels of physical activity and the fasting plasma glucose/insulin ratio (r = 0.371, P < .01) or the fasting serum insulin concentration (r = -0.282, P < .05). The study provided evidence that a low level of leisure time physical activity is associated with insulin resistance and resultant hyperinsulinemia, which are the key metabolic abnormalities that link hypertension, obesity, and hyperlipidemia in young subjects. PMID- 1285942 TI - Sustained hypertension in the rat induced by chronic blockade of nitric oxide production. AB - It is well established that acute systemic blockage of L-arginine conversion to nitric oxide by NW-nitro-L-arginine methyl ester (L-NAME) and other substituted analogs of L-arginine produces vasoconstriction and elevates the blood pressure. The present study in rats reports that chronic L-NAME injections (185 mumol/L/kg body weight, intraperitoneally; every 12 h) for 4 days produces sustained arterial hypertension which is fully and rapidly reversed by acute administration of excess L-arginine. The magnitude of the hypertension is not different between L-NAME treated rats fed normal or high sodium diets. The results from this simple experimental model suggest that chronic blockade of nitric oxide synthesis results in sustained arterial hypertension that is not enhanced by sodium loading. PMID- 1285944 TI - Beyond diagnosis of left ventricular hypertrophy in patients with essential hypertension. PMID- 1285943 TI - Angiotensin converting enzyme inhibition of renin system activity induces reversal of hypertensive target organ changes. Do these effects predict a reduction in long-term morbidity? PMID- 1285945 TI - Gene therapy for hypertension. PMID- 1285946 TI - A note about Khoury et al's "The early morning rise in blood pressure is mainly related to ambulation". PMID- 1285947 TI - Sodium intake and salt sensitive hypertension. PMID- 1285948 TI - Opposite effects of rough and gentle handling with repeated saline administration on c-fos mRNA expression in the rat brain. AB - The rough handling with repeated saline administration (1.2 ml/kg s.c. for 7 days) enhanced cortical c-fos mRNA expression in the rat brain after a single saline stimulation (1.2 ml/kg s.c.) due to increasing baseline c-fos mRNA levels, whereas the gentle handling with repeated saline administration declined c-fos mRNA expression after a single injection due to decreasing the baseline of c-fos mRNA levels. These two types of handling with the repeated injection led to diametrically opposite results on c-fos mRNA expression after a single stimulation. Neither two types of handling with repeated saline injections affected the net increment of c-fos mRNA induction after a single stimulation, therefore, the effects of handling with repeated treatment on c-fos mRNA expression might be independent of the effects of a single saline stimulation. The present study suggests that c-fos mRNA induction after a single stimulation might be affected by the types or intensities of handling and that care must be taken to estimate c-fos mRNA induction. PMID- 1285950 TI - MK-801 induced stereotypies in rats are decreased by haloperidol and increased by diazepam. AB - The effects of haloperidol and diazepam were investigated on stereotypies (wall contacts and turn rounds) induced by the non-competitive NMDA antagonist MK-801 in rats. Haloperidol (0.03, 0.10, 0.25 and 0.40 mg/kg body weight) caused a dose dependent antagonism whereas diazepam (3.0 and 5.0 mg/kg) caused a dose-dependent agonism of the stereotypies induced by 0.30 mg/kg MK-801 (all drugs given intraperitoneal). Conversely, diazepam (5.0 mg/kg) given alone reduced significantly the number of spontaneous wall contacts and turn rounds. The paradoxial stimulation of MK-801 induced stereotypies by diazepam could be explained by a shift between positive and negative corticostriatothalamic feedback loops envolving GABAergic neurons in favour of the former. PMID- 1285949 TI - Muscarinic cholinergic receptor-mediated modulation on striatal c-fos mRNA expression induced by levodopa in rat brain. AB - To clarify the interactions between dopamine receptors and muscarinic cholinergic receptors by which neurotransmitters may affect genetic responses, we studied the effects of the muscarinic cholinergic agonist, carbachol, and the muscarinic cholinergic antagonist, trihexyphenidyl, on levodopa-induced c-fos messenger RNA (mRNA) expression in rat striatum. Animals were administered levodopa (levodopa with one-tenth dosage of carbidopa), carbachol or thrihexyphenidyl alone or administered in combination as levodopa (100 mg/kg) + carbachol, or levodopa+trihexyphenidyl given as a single bolus. Levodopa given alone increase the expression of c-fos mRNA. Although carbachol or trihexyphenidyl alone was ineffective in inducing c-fos mRNA, the combination of levodopa and carbachol (> or = to 0.1 mg/kg) significantly suppressed the induction of c-fos mRNA as compared with levodopa given alone. The combined administration of levodopa and trihexyphenidyl showed a trend toward an additive effect on the induction of c fos mRNA vs levodopa alone. These findings suggest that the muscarinic cholinergic system may modulate the levodopa-induced c-fos mRNA expression which then regulates the expression of other mRNAs. PMID- 1285951 TI - Gamma-aminobutyrate aminotransferase activity in brains of schizophrenic patients. AB - The activity of gamma-aminobutyrate aminotransferase (GABA-T) was estimated in twelve regions of brains from 22 control subjects and 6 cases with schizophrenia. In the controls, no significant correlation was found between the enzyme activity and age or postmortem interval (PMI) in any of the brain regions studied. In experiments on rat brains, the enzyme activity decreased about 20% during the first 2 hours of storage at room temperature and at 4 degrees C but remained steady thereafter. A similar initial decline in activity in the human brain material cannot be excluded. In the human brains, a slightly lower activity was found in the group below 75 years (n = 8) when compared with the group above 75 years (n = 8). A tendency to higher activities was found in female brains (n = 10) compared with male brains (n = 12). No significant difference in the enzyme activity was found between schizophrenic brains, in any of the regions studied, when compared to controls, matched for age, sex and PMI. PMID- 1285952 TI - Radius of curvature as a novel diagnostic tool for facial esthetics. PMID- 1285953 TI - Detection of tumor necrosis factor in gingival crevicular fluid. PMID- 1285955 TI - Educational programs at Northwestern 1991-92. PMID- 1285954 TI - Effect of starting notch diameter on fracture toughness. PMID- 1285956 TI - The effect of size characteristics of alveolar cleft defects on bone graft success: a retrospective study. PMID- 1285957 TI - Temporal evaluation of juvenile and adolescent skeletofacial growth rates. PMID- 1285958 TI - Coronariographic significance of heart rate variation related to ischemic episodes in patients undergoing peripheral vascular surgery. AB - OBJECTIVES: To evaluate the characteristics of myocardial ischemia during daily life and their coronariographic significance in a group of patients with proven coronary artery disease undergoing peripheral vascular surgery. SETTING: Department of Cardiology--Central Hospital--Lisbon. METHODS: In 14 patients undergoing peripheral vascular surgery and in whom coronariography revealed coronary significative lesions, Holter monitoring was performed during a 24-hour period. Two groups of ischemic episodes were considered: Group A constituted by 44 episodes detected in patients with left main or three vessel disease and group B by 12 episodes detected in patients with one ot two vessel disease. In each group the ischemic parameters were studied. RESULT: The incidence of myocardial ischemia was 64%. Statistically significant differences were observed between group A and B concerning the mean heart rate variation from two minutes before the onset of ST-segment depression to its onset (2.39 bpm vs 8.75 bpm; p < 0.05), from the onset of ST-segment depression to its maximal depression (4.43 bpm vs 16.67 bpm; p < 0.001) and from two minutes before St-segment depression to its maximal depression (6.82 bpm vs 25.4 bpm; p < 0.00001). No differences were found in duration and maximal ST-segment depression. CONCLUSION: Particular characteristics of heart rate variation related to the ischemic episodes seem to have a relation with the severity of coronary artery disease in patients undergoing peripheral vascular surgery. PMID- 1285959 TI - The usefulness of continuous vectorcardiography in patients with myocardial infarction and unstable angina. PMID- 1285961 TI - [The use of diuretics in heart insufficiency in the elderly]. AB - The kidney function alterations with age and on congestive heart failure, are reviewed as the pharmacocynetic and pharmacodynamic of the diuretics on old patients with this syndrome. The therapeutic importance of hiposodic diet was considered. The reasons for the susceptibility of old people to diuretics and the criteria for the choice of the diuretic on this age, are reviewed. So are the most important adverse effect of diuretics on old people and the contra indication for the use of these drugs on elderly. The importance of hypocalaemia on old people and how to prevent or correct it are considered. The haemodynamic risks of an excessive diureses are reviewed. Finally, we propose some recommendations about the use of diuretics on the elderly. PMID- 1285960 TI - Late arrhythmic events and patency of the infarct-related coronary artery in survivors of acute myocardial infarction. AB - In the present study we evaluated the influence of intravenous thrombolysis and patency of the infarct-related coronary artery on both markers of ventricular electrical instability and incidence of late arrhythmic events after acute myocardial infarction (AMI). Ninety one patients surviving a first AMI who consecutively performed coronary angiography were enrolled in the present study; 44 patients (48%) received thrombolysis, 47 patients (52%) were treated conventionally. Of 91 patients, 90 (99%) had signal-averaged electrocardiogram (SAECG), and 40 (44%) programmed ventricular stimulation. No significant difference was observed between thrombolytic-treated and control group in late potential rate, SAECG determinants and ventricular arrhythmia inducibility. Of 91 patients, 40 (44%) had occlusion of the infarct-related artery: of these, 15 (37%) had late potentials compared with 5 of 51 patients (9%) with a patent artery (p < 0.01). Mean left ventricular ejection fraction was not significantly different between the two groups (0.50 +/- 0.15 vs 0.55 +/- 0.12; p = NS). No significant difference was present between the two groups of patients with regard to inducibility of sustained ventricular tachyarrhythmias, however an odds ratio of 3.5 was observed in the group with a closed vessel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1285962 TI - [Two cases of endomyocardial fibrosis in Mozambique]. AB - This essay describes two cases of Endomiocardial Fibrosis with right ventricular dominance studied in Mozambique. The clinical, radiological, echocardiographic and patological findings are in accordance with other descriptions of same disease, seen in others countries. PMID- 1285963 TI - [Dilated myocardiopathy: value of isotopic studies for its clinical characterization]. PMID- 1285964 TI - Endothelium disfunction in coronary artery disease. PMID- 1285965 TI - The role of endothelial dysfunction in restenosis. PMID- 1285966 TI - [A surgical technique for high aortic occlusions]. AB - The authors analyze the technical aspects of aortic prosthesis in 37 patients with atherosclerotic, high occlusions of the aorta. The upper occlusion limit in this abnormality is shown to have two X-ray variants. Thoracophrenolumbotomy is considered to be the best access for proximal anastomosis in aortic prosthesis. The traditional operation technique for this abnormality has some disadvantages, the main limit of which is the necessity of shifting a patient from place to place for proximal and distal anastomoses. This makes the operation in these severe patients longer. The authors have proposed a novel procedure for aortic prosthesis by employing a special roller. The latter eliminates the necessity of shifting the patient from place to place during surgery, cuts surgical time by more than 2 hours, allows one to follow asepsis more carefully. PMID- 1285967 TI - [The use of polytetrafluoroethylene vascular prostheses (Gore-Tex) for subclavian pulmonary anastomosis in children with tetralogy of Fallot]. AB - The paper provides the results of a modified subclavian pulmonary anastomosis by employing Gore-Tex vascular prostheses in 91 babies with Fallot's tetrad whose age was 10 days to 32 months and weight was 3.6 to 15 kg. In 89 patients, the operation was performed by using a prosthesis, 4-6 mm in diameter, without crossing the subclavian artery, whereas in 2 patients, this was done by lengthening the crossed short subclavian artery. In the early postoperative period, 2 (2.2%) patients died, anastomosis thrombosis requiring a reoperation, occurred in 3 (3.3%) patients; other non-fatal complications were observed in 8 (8.8%) patients. A clear-cut effect of the operation was seen in all patients. SaO2 rose from 54 +/- 18 to 80.0 +/- 8%. In the long-term (6-60 months) postoperative periods, a total of 77 patients were examined: anastomosis function proved to be impaired in 4 (5.2%), all the vascular prostheses, 6 mm in diameter, were patent up to 60 months of surgery. The thrombosis probability for anastomosis, 5 mm in diameter, was 5% during 12 months of operation and 16% during 24-60 months. Three patients needed therapeutical management of heart failure. Other serious complications, including deformity of the pulmonary artery or upper extremity, were not found in the examinees. In the palliative treatment of Fallot's tetrad, subclavian pulmonary anastomosis via the Gore-Tex vascular prosthesis can be the method of choice in the first-year-old infants and has some substantial advantages over the classical Blelock-Taussig anastomosis. PMID- 1285968 TI - [Methods of plastic surgery of the renal arteries in children with vasorenal hypertension]. AB - The work deals with the management of vasorenal hypertension in children and adolescents. The Bakulev Institute of Cardiovascular Surgery had 185 children with arterial hypertension from 1965 to 1990. Their ages ranged from 12 months to 17 years. The vasorenal genesis of hypertension was caused by fibromuscular dysplasia (FMD) of the renal arteries in 61 patients, unspecific aortoarteritis (UAA) in 39, hypoplasia of the abdominal aorta, kidneys, and renal arteries in 22 patients, supernumerary renal arteries were found in 7 patients. A total of 119 operations were carried out on 106 patients. Operations and one-stage revascularization of the kidneys and alimentary organs were performed on 22 patients, isolated reconstruction of the renal arteries on 51 patients. Among 99 patients with stenoses and aneurysms of the renal arteries 13 were treated by nephrectomy (11.3%). The postoperative mortality was 0.9%. A hypotensive effect was not produced in the immediate postoperative period in 5 patients with UAA (4.6%) and in one patient with, FMD (0.9%). Six operations were performed in late term periods after the first operative interventions: 2 for aneurysm of autovenous grafts, 2 for restenosis of the renal arteries, and 2 for stenosis of the aorta distal to the primary site of reconstruction in UAA. Three patients died in the late-term periods. The stability of good operative results was highest in congenital hypoplasia of the aorta--100%. A favorable effect of the operation persists in 89.6% of patients with FMD of the renal arteries. The stability of the effect is lowest (75%) in UAA. PMID- 1285969 TI - [The treatment of critical valvular stenosis of the pulmonary artery by the balloon valvuloplasty method in patients in the first 3 years of life]. AB - The work generalizes the experience of the Bakulev Institute of Cardiovascular Surgery in balloon valvuloplasty of valvular pulmonary stenosis in 58 children of the first 3 years of life: 8 were 1 to 6 months of age, 10 were 7 to 12 months of age, 18 were 13 to 24 months old, and 22 were 25 to 36 months old. Cyanosis was found in 27 of them. As the result of balloon valvuloplasty, the systolic pressure gradient between the right ventricle and the pulmonary artery reduced from 114.7 +/- 12.6 to 31.4 +/- 7.2 mm Hg in children under 1 year of age, from 143 +/- 12.6 to 40.1 +/- 8.3 mm Hg in children aged from 1 to 3 years. In patients with cyanosis, saturation of arterial blood with oxygen increased to 92%. The late-term results were studied in follow-up periods of 6 to 36 months in 35 patients, by means of catheterization and angiocardiography in 15 of them. Analysis showed balloon valvuloplasty to be effective. Balloon valvuloplasty was repeated in 5 patients with critical stenosis because a hemodynamic effect was not achieved by the first dilatation. PMID- 1285970 TI - [Cardiac abscesses]. AB - The paper analyzes the experience in treating 75 patients with cardiac abscesses of various sites. Abscesses complicated the natural history of infectious endocarditis in all patients. The clinical features of cardiac abscesses are shown to be related to the stage of the destructive process. Echocardiography, follow-up analysis of ECH, PhCG and overall clinical data are demonstrated to play a role in their diagnosis. The paper discusses the specific features of surgical intervention into the heart if abscesses are present. Out of 75 patients who have been operated on for abscessing infectious endocarditis, 53 have had an operation and survived. PMID- 1285971 TI - [Characteristics of the blood flow in the vertebral artery before and after the surgical treatment of the proximal segment of the subclavian artery]. AB - The features of the blood flow in the vertebral artery were studied by ultrasonic dopplerography with functional test for reactive hyperemia in 52 patients. The authors claim this to be an objective screening method allowing the sequelae of occlusion of the vertebrosubclavian segment to be studied and providing information for establishing the diagnosis and appraising the efficacy of reconstructive operations. PMID- 1285972 TI - [Schemes for implanting shovel pumps for assisted circulation]. AB - The authors propose a design of an axial shovel pump for extracorporeal circulation. They show how to introduce it into various cardiovascular segments and make a comparative assessment of its efficacy in relation to the type and severity of heart failure, surgical access, and treatment policy. PMID- 1285973 TI - [Age and dyslipidemia as risk factors in transcutaneous transluminal angioplasty]. AB - The paper outlines the analysis of immediate and late outcomes of transcutaneous transluminal angioplasty (TTA) in 147 patients with atherosclerosis obliterans of the lower extremities. The study has revealed that age and dyslipidemia as TTA risk factors fail to affect the immediate outcomes in the early postoperative period. There is a positive correlation of the reocclusion time after TTA and the age and lipid metabolic disturbances in patients with atherosclerosis obliterans of the lower extremities in long-term periods. The paper provides strong evidence for that it is essential to correct dyslipidemias in order to make TTA results better in these patients. PMID- 1285974 TI - [A comparative evaluation of myocardial protection based on criteria not associated with the quality of myocardial conservation]. AB - Based on the rich clinical material (405 patients), the authors have assessed the most common blood and crystalloid cardioplegic techniques by applying the criteria which do not apply to those of myocardial protection adequacy. Differences have been found between the methods in the volumes of blood loss, the number of patients operated on without utilizing donor blood, terms of aortic occlusion at one-stage operative interventions, recovery of cardiac performance after aortic occlusion. The differences found are essential in choosing the type of cardioplegia by taking into account the individual traits of each surgical intervention and an operating surgeon's opinions. PMID- 1285975 TI - [Surgical tactics in pleural empyema with regard to the use of a carbon dioxide laser and argon plasma]. AB - The authors analyze the experience gained in treating 30 patients with acute and 23 with chronic pleural empyema. The management policy identified the following points. Laser thoracoscopic necrectomy and empyemic cavity sanitation are indicated in acute destructive pulmonitis. A combination of temporary bronchial occlusion and laser treatment of the empyemic cavity and bronchopleural fistula should be performed after debridement of a destructive pulmonitis area from necrotic tissues. Radical treatment of chronic pleural empyema should be better conducted in the early periods by employing a plasma scalpel at all the stages of surgical intervention for hemostasis, aerostasis and sterilization of the operation field. PMID- 1285977 TI - [Diagnosis and treatment of complex closed chest injuries]. AB - The results of treatment of 256 patients with complicated closed chest injury are discussed. Multiple fractures of the ribs were found in 178, closed pneumothorax in 127, pneumohemothorax in 71, isolated hemothorax in 55, and rupture of the diaphragm in 3 patients. Most patients received nonoperative treatment, 5 patients (6.1%) needed emergency thoracotomy. Early drainage of the pleural cavity, endoscopic (thoracoscopy, bronchoscopy) methods of treatment, mechanical stabilization of floating rib fractures made it possible to improve the results and reduce the terms of treatment. Two (0.8%) persons died from shock and cardiopulmonary insufficiency. PMID- 1285976 TI - [Parasternal mediastino-pleuroscopy in the diagnosis of diffuse lesions of the lungs]. AB - A procedure for parasternal mediastinopleuroscopy (PMS) has been proposed for biopsy of pulmonary tissue and intrasternal lymph nodes. A surgical technique of intervention is described in the paper. PMS was performed in 81 patients with diffuse lesions of the lungs and the disease was morphologically verified. The clinical and X-ray diagnosis was found to be incoincident with their final morphological diagnosis after PMS had been performed in 48 out of 81 patients. To obtain an informative biopsy specimen needed for a morphological diagnosis, biopsies of the lung and lymph nodes should be taken in all cases. Complications occurred in 2 patients. These included bleedings from the intercostal arteries, which required vascular ligation. PMID- 1285978 TI - [Emergency repeated operations for lung cancer]. AB - A total of 43 patients with surgical complications developed after planned surgeries for cancer of the lung were followed up in the Thoracal Oncological Clinic, Cancer. Research Center, Russian Academy of Medical Sciences, in 1981 1990. Emergency repeated operations for complications were performed in 23 (53.4%) of them. Bronchial suture insufficiency after various pulmonary resections occurs in 2.4% of cases in 25 out of 1030 patients). Intrapleural hemorrhages after resection of the lung result from technical errors of a surgeon during mobilization of the lung or lymphadenectomy (in 10 out of 14) and they are infrequent during treatment of pulmonary or lobal blood vessels (in 4 out of 14). Impaired seal of lung parenchymal sutures, which needs active surgical policy, was seen in 2 out of 1030 patients with lung resection. Our clinical material shows that chylothorax as a complication of pulmonectomy is associated with a rare left-sided location of the thoracic lymph duct. In pulmonary cancer, active surgical policy has advantages over conservative therapy: the mortality was 8.0% (2 out of 25) and 25.9% (7 out of 27), respectively. Conservative therapy of patients with bronchial suture insufficiency is preferable after pulmonectomy. Emergency repeated operations in the early period are preferable in these complication after pulmonectomy. PMID- 1285979 TI - [The invasion of a tumor into the bronchial wall in central cancer of the lung]. AB - The paper analyzes histological findings of a number of bronchial sections made proximal the visible margins of a tumor in 54 patients operated on for central cancer of the lung. In coincidence of micro- and macroscopic limits of the extension of tumor cells was revealed in 29 (53.7%) patients. Statistical analysis revealed that the extension of tumor invasion obeys the exponential law of distribution. Probability of detecting tumor cells at various distances from the visible margin of the tumor was found. The findings suggest that one may predict that tumor cells can remain in the bronchial stump depending on the level of its elimination. PMID- 1285980 TI - [Complications of phlebosclerosing therapy, their prevention and treatment]. PMID- 1285981 TI - [Prosthesis of the incompetent mitral valve with preservation of the subvalvular structures]. PMID- 1285982 TI - [Buchwald's operation in the surgery of atherosclerosis obliterans]. AB - Analyzing the world's experience in the surgical management of hyperlipidemias and their own results, the authors make an assessment of Buchwald's operation used in the surgery for atherosclerosis obliterans. The major disadvantage of partial ileac bypass is that there is no prognosis of the operation and its complication. Based on the pathophysiological mechanisms of implementation of Buchwald's operation, the authors have developed a mode of pharmacological simulation of a partial bypass which allows one to predict the effect of the impending intervention and to avoid unjustified operations. The unique procedure also enables the indications for simultaneous interventions to be defined. Ten partial ileac bypass surgeries made by the authors are comprehensively analyzed. Taking into account, the authors propose to choose a treatment of patients with hyperlipidemia and atherosclerosis on an individual basis and to do away with the routine indications for partial ileac bypass surgery. PMID- 1285983 TI - [Correction of an aortic coarctation combined with a false aortic aneurysm in an infant]. PMID- 1285985 TI - [A gigantic echinococcal cyst simulating a spontaneous pneumothorax]. PMID- 1285984 TI - [The surgical treatment of tachyarrhythmia in a patient with occlusive disorders of the magistral vessels]. PMID- 1285986 TI - [Annuloplasty of the tricuspid valve with a controllable semi-ring under the control of transesophageal echocardiography]. AB - The paper analyzes the first clinical experience with a novel procedure of tricuspid annuloplasty with a controllable semiring under the control of transesophageal echocardiography in 6 patients with tricuspid dysfunction and those with mitral and tricuspid valvular diseases. The application of intraoperative transesophageal echocardiography makes it possible to control both the degree of mitral regurgitation and the severity of right atrioventricular stenosis. This echocardiography may serve a method for plastic correction of the tricuspid valve. PMID- 1285987 TI - [Cytogenetic diagnosis of brain tumors]. PMID- 1285988 TI - [Immune defense mechanism in the central nervous system--role of microglia and astrocytes]. PMID- 1285989 TI - [Benign brainstem encephalopathy with truncal ataxia--a clinical study of 3 cases]. AB - Three cases (case 1, female, aged 30; case 2, male, aged 32; case 3, male, aged 34) of benign brainstem encephalopathy with truncal ataxia were reported. Two patients had prodromal symptoms Neurological examination revealed truncal ataxia in all cases. As additional neurological signs, anisocoria, mydriasis, nystagmus, ptosis, transient opsoclonus, and facial palsy were seen. There was neither drowsiness nor myoclonus in the three cases. On laboratory examinations, cold agglutination test revealed significant elevation in two cases. The examination of cerebrospinal fluid showed a moderate rise of proteins in one case, but did not revealed pleocytosis in any of the cases. Magnetic resonance imaging of one patient revealed an area of high intensity in the left pontine tegmentum by T2 weighed imaging. The prognosis for all these cases was good, and the reappearance of neurological signs was not present until now. Our cases were different from brainstem encephalitis (Bickerstaff's encephalitis) because of an absence of disturbed consciousness and no pleocytosis in the cerebrospinal fluid. Our cases were also different from "myoclonus-opsoclonus syndrome" because of an absence of myoclonus. We discussed a possibility of a new clinical syndrome which we call "benign brainstem encephalopathy with truncal ataxia". PMID- 1285990 TI - [High-field-strength magnetic resonance imaging and SPECT of multiple system atrophy]. AB - Two cases of multiple system atrophy (MSA) showing similar abnormalities by magnetic resonance (MR) imaging and SPECT are reported. The clinical diagnoses of the two cases were striatonigral degeneration (SND) and sporadic olivopontocerebellar atrophy (OPCA). In addition, one case of sporadic OPCA without parkinsonism was used for comparison. The MR images were obtained using a 1.5-T MR system and included spin-echo transverse sections with T1-weighted images (TR = 450 ms and TE = 15 ms) and T2-weighted images (TR = 2500 ms and TE = 90 ms). The T1-weighted images demonstrated atrophy of cerebellum and pons, with increased signal intensity in the bilateral putamen. The T2-weighted images demonstrated decreased signal intensity in the putamen, as reported recently. SPECT demonstrated reduced uptake in the celleberum, basal ganglia and frontal lobe cortex. The putaminal changes evident on T1-weighted images may have resulted from deposition of pigments such as neuromelanin and lipofuscin, related to parkinsonism. Both T1- and T2-weighted MRI seem to be useful clinical diagnosis of MSA. PMID- 1285991 TI - [Pathogenesis of hyponatremia observed in the treatment of acute subarachnoid hemorrhage]. AB - The cause of hyponatremia following subarachnoid hemorrhage (SAH) has been understood as an inappropriate secretion of antidiuretic hormone (SIADH). Whereas, water restriction for the management of this condition sometimes induces a severe dehydration, resulting in vasospasm. To clarify the pathogenesis of hyponatremia following SAH, we measured the daily sodium and water balance with the plasma concentration of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in seventeen cases after subarachnoid hemorrhage. Although the patients received an adequate amount of fluid (more than 4080ml/day; daily average in seventeen cases) and sodium (more than 277 mEq/day; daily average in seventeen cases), eight out of the seventeen cases showed transient hyponatremia of a slight degree beginning on 8.8 days after SAH. ANP values were elevated markedly in fifteen out of the seventeen cases, remaining high during the first two weeks following SAH. ADH values were elevated remarkably in eight out of the seventeen cases. However, these values declined immediately to a normal range within two days following SAH. PRA were increased or came within the normal range, suggesting the lack of water retention. Overall sodium balance and water balance did not differ significantly between hyponatremia cases and normonatremia ones, whereas, sodium balance in acute phase was significantly negative, associated with marked natriuresis in patients with hyponatremia. These correlations suggested that hyponatremia after SAH is the result of natriuresis by an increased ANP rather than ADH. In conclusion, a greater replenishment of water and sodium is required to avoid hyponatremia with dehydration. This technique may be helpful for the prevention of vasospasms following SAH. PMID- 1285992 TI - [A case of steroid psychosis associated with betamethasone]. AB - Psychotic side effects of steroids have been observed at relatively high frequency if mild cases, such as euphoria, are included, while it has been said that incidences differ among kinds of steroids. We reported a case developing severe schizophrenia-like symptoms following the treatment with betamethasone although this drug is believed to be rarely involved in steroid-induced psychosis, and its psychotic side effects have been rarely reported. When betamethasone was administered for progressive peripheral facial paralysis at a mean daily dose of 7mg, psychotic symptoms appeared from the 15th treatment day. Psychosis began with interrupted appearance of excitation, autism, and misanthropia. Although the steroid was gradually decreased in dose because of abatement of facial paralysis, not only psychotic symptoms were aggravated, but also appeared hallucination. Thus the steroid was withdrawn before the scheduled date while its dose was gradually decreased, and haloperidol was administered. Psychotic symptoms were gradually eliminated and completely disappeared about 40 days after onset. PMID- 1285993 TI - [Acoustic neurinoma associated with facial neurinoma--a case report]. AB - A 38-year-old man developing slowly progressive left facial paresis was admitted to our hospital. The clinical diagnosis of "adhesive arachnoiditis was made. The first operation was performed in December 1987, and his symptom disappeared postoperatively. Three years later, left facial paresis recurred together with trunkal ataxia. A computed tomography and magnetic resonance image revealed two tumors located at the left cerebellopontine angle region and in the left middle cerebral fossa. These two tumors were thought to arise in the different cranial nerve. Under the clinical diagnosis of acoustic neurinoma associated with facial nerve neurinoma, the two step-operation was designed for total removal of the tumor in December 1990 and January 1991. Intraoperative finding confirmed that these two tumors had the different origin. Pathologic diagnosis was compatible with neurinoma. This patient had no family history of "Neurofibromatosis". PMID- 1285994 TI - [A case of Castleman's disease with a variable neuropsychiatric symptomatology]. AB - A case of 44-year-old woman who had shown psychiatric symptoms before and during the course of Castlemans' disease was presented. For four years, she first suffered from a paranoid-hallucinatory state and then a depressive one episodically. In the course of the latter, severe anemia developed. She was diagnosed as Castleman's disease, because the increased serum level of gamma globulin and interleukin-6 (IL-6), and multiple lymphomata were evidenced. A paranoid-hallucinatory state relapsed about one year later from this episode. At last, some bulbar and cerebellar symptoms, and a delirium suddenly occurred. The ischemic changes at the level of the pons and midbrain were revealed by the magnetic resonance imaging (MRI) examination. It is certainly that both neurological and psychiatric symptoms were related to the lesions. This ischemic lesions may have resulted from the anoxia secondary to the severe anemia and/or hyperviscosity syndrome in the disease. On the other hand, the increased serum level of IL-6 as well as the ischemic lesions might have caused psychiatric symptoms in this case, as the interferone which is one of the analogues of IL-6, is known to induce emotional and behavioral symptoms. PMID- 1285996 TI - [Brainstem glioma with supratentorial meningeal dissemination--a case report]. AB - We present a very rare case of 7 year-old-girl who had a pontine glioma with supratentorial meningeal involvement. She complained severe headache with meningeal irritation. She showed fluctuating cranial nerve impairment of the both abducens and glosopharyngeal nerves but no signs of weakness or facial paresis. She also reported two episodes of generalized convulsion with unconsciousness during admission. MRI disclosed a hypointensity intrinsic brainstem mass with an enhancing exophytic component in the prepontine cistern and a sharp contrast uptake is disclosed in the left-meninges of the supratentrial structures. An open biopsy was performed and diagnosed as a high grade astrocytoma. PMID- 1285997 TI - Dermatology Nursing Scope of Practice and Dermatology Nursing Standards of Clinical Nursing Practice. DNA standards and certification committee. PMID- 1285998 TI - DNA proudly introduces Dermatology Nursing Scope of Practice and Dermatology Nursing Standards of Clinical Nursing Practice documents. PMID- 1285999 TI - Dermatology Nursing Standards of Clinical Nursing Practice: ensuring a level of competency. AB - Nursing can take charge of its professional practice by setting standards of clinical practice based on nursing expertise. Standards of Dermatology Clinical Nursing Practice can ensure competency and improve the quality of clinical care and consumer decision making. PMID- 1285995 TI - [A case of malignant melanoma with orbital metastasis which caused the first symptoms]. AB - A thirty-four-year-old man was admitted to our hospital because of the disturbed visual acuity and pain on the eye movement of the right eye. He had prominent right eye and CT-scan and MRI of the brain disclosed a tumor which could be obviously distinguished from the extraocular muscles, optic nerve and the bulb of eye in the retrobulbar region. On operation we identified dark-red solid tumor which was 3.0cm in diameter, and diagnosed it malignant melanoma pathologically. Because postoperative study detected amelanotic melanoma in the white patch on the right upper extremity, this right orbital tumor was considered to be the metastasis of it from the right upper extremity. Metastatic malignant melanoma of the skin to the orbit is very rare, while most of the eye-associated malignant melanoma originates from uveal tract, special choroid, and conjunctiva. This case was the 26th case of these in the world and the first case in Japan, furthermore the 4th case in the world whose first symptoms were caused by the orbital metastasis. PMID- 1286000 TI - Dermatology Nursing Standards of Clinical Nursing Practice: what does it mean to our professional practice? AB - Standards of care and professional performance are the backbone of dermatology nursing practice as well as the basis for professional growth and development. The goal of developing Dermatology Nursing Standards of Clinical Nursing Practice is to gain formal recognition for the practice of dermatology nursing. PMID- 1286002 TI - What's your assessment? Lichen planus. PMID- 1286001 TI - Management of rosacea. AB - Rosacea is a skin dysfunction affecting a large number of individuals. The cause is unknown and there is no known cure. Once the condition is recognized, however, much can be done to reduce the extent and impact of this disease. PMID- 1286003 TI - The drug research process. AB - The Department of Dermatology at the Washington Hospital Center conducts research on drugs and products for various drug companies prior to their approval by the Food and Drug Administration. The purpose of this article is to describe this interesting and rewarding process which can give dermatology nurses the opportunity to assist patients who might not have found effective or affordable treatment for their condition. PMID- 1286004 TI - Support group for persons with albinism. PMID- 1286005 TI - Centriole modification in human aortic endothelial cells. AB - The structure of centrioles in endothelial cells of embryonic (22-24 weeks old) and definitive (2, 14-17, and 30-40 years) human aorta in situ and also in aortic endothelial cells dividing in organ and cell cultures (donor age 30-40 years) was studied. It was found that in the endothelial cells from definitive aorta the lengths of mother centrioles vary from 0.5 to 2 microns, whereas the length of daughter centrioles remains constant (0.4-0.5 microns). The distal part of the cylinder of long mother centrioles consists of microtubule doublets. In aorta of donors 30-40 years old in multinucleated cells and in one of 30 single-nucleated cells analyzed, C-shaped long centrioles were seen. These centrioles exhibit a doublet organization along all their length. Mitotic cells in organ and cell culture had a nonequal structure of spindle poles: at one pole, the long mother centriole was seen, while at the other a mother centriole of standard size was found. In such cells of organ culture long centrioles make contact with the remnant of primary cilia until the end of anaphase. In cell culture mitotic cells are also observed containing C-shaped centrioles. In these cells the number of mother centrioles is odd and their number is not equal to the number of daughter centrioles. The possible mechanism for transformation of endothelial centrioles and its role in the control of cell-cycle progression are discussed. PMID- 1286006 TI - Hydrogen bonding of iron-coordinated histidine in heme proteins. AB - The hydrogen-bonding motifs of the proton on the N delta atom of iron-coordinated histidine residues in heme proteins have been classified into three categories: (1) Those in which the hydrogen-bond acceptor is either an amino acid residue (serine) directly adjacent to the histidine or a carbonyl group of the polypeptide chain less than five residues away from the histidine; (2) those in which the hydrogen-bonding acceptor is a carbonyl group of the polypeptide backbone associated with an amino acid residue 8 to 17 residues away from the histidine; and (3) those in which the hydrogen-bonding acceptor is an exogenous water molecule or an amino acid residue located far from the histidine in the amino acid sequence. Some biological functions are defined by this classification, whereas others span all classes. PMID- 1286007 TI - The rigidity of bacterial flagellar filaments and its relation to filament polymorphism. AB - We determined and correlated the rigidity of Salmonella typhimurium, Escherichia coli, and Rhizobium lupini flagellar filaments representing various structural and polymorphic states (plain, complex, straight, superhelical, and right- and left-handed). Persistence length, from which the filament's rigidity and other parameters (Young's modulus, bending force constant, buckling persistence length, flexural deformation, and flexural time) were derived, was determined from electron micrographs of isolated, negatively stained filaments. Outer diameters and radii of strong intersubunit connectivity were determined from three dimensional image reconstructions and radial mass density profiles from scanning transmission electron microscopy. All filaments appear to be highly rigid with no evident correlation with their helical sense or superhelicity. The complex filament of R. lupini is rigid to the extent that it becomes brittle. The overall flexibility of the flagellum seems to stem mainly from the hook and not from the filament. Polymorphism is probably related to the propelling properties and hydrodynamic shape of the filament rather than to its rigidity. PMID- 1286008 TI - X-ray solution scattering studies on vinblastine-induced polymers of microtubule protein: structural characterisation and effects of temperature. AB - We report here on X-ray solution scattering and electron microscopy studies of microtubule protein in the presence of the antimitotic drug, vinblastine. In buffer conditions used for microtubule assembly, vinblastine caused the formation of coil-like structures. The coils appeared to be made up of two protofilaments. Details of the structure and behaviour of coils in solution were obtained from interpretation of their solution scattering patterns. Upon increasing temperature from 4 to 37 degrees C the pitch of the coils increased from 25.92 to 26.96 nm. However, little change was observed in their mean diameters (38.46 and 38.45 nm, respectively). Increasing the temperature also favoured increased formation and/or elongation of the coils. The effect of temperature on the pitch was fully reversible. Vinblastine-induced assembly of pure tubulin also showed the formation of coils. However, these coils appeared to consist of only one protofilament. Their mean diameters (38.35 nm) were similar to those of the coils formed from microtubule protein. PMID- 1286010 TI - Mastalgia mostly merits masterly inactivity. PMID- 1286009 TI - Configuration of interdomain linkers in pyruvate dehydrogenase complex of Escherichia coli as determined by cryoelectron microscopy. AB - The dihydrolipoyl transacetylase (E2p) component of the pyruvate dehydrogenase complex (PDC) of Escherichia coli is a multidomain polypeptide comprising a catalytic domain, a domain that binds dihydrolipoyl dehydrogenase (E3-binding domain), and three domains containing lipoic acid (lipoyl domains). In PDC 24 subunits of E2p associate by means of interactions involving the catalytic domains to form the structural core of PDC. From cryoelectron microscopy and computer image analysis of frozen-hydrated isolated E2p cores it appears that the lipoyl domains are located peripherally about the core complex and do not assume fixed positions. To further test this interpretation the visibility of the lipoyl domains in electron micrographs was enhanced by specifically biotinylating the lipoic acids and labeling them with streptavidin. In agreement with the studies of native, unlabeled E2p cores, cryoelectron microscopy of the streptavidin labeled E2p cores showed that the lipoic acid moieties are capable of extending approximately 13 nm from the surface of the core. Localization of the E3-binding domains was accomplished by cryoelectron microscopy of E2p-E3 subcomplexes prepared by reconstitution in vitro. Frequently an apparent gap of several nanometers separated the bound E3 from the surface of the core. The third component of PDC, pyruvate dehydrogenase (E1p), appeared to bind to the E2p core in a manner similar to that observed for E3. These results support a structural model of the E2p core in which the catalytic, E3-binding, and three lipoyl domains are interconnected by linker sequences that assume extended and flexible conformations. PMID- 1286011 TI - Clinical evaluation of murmurs in pregnancy. PMID- 1286012 TI - Cyclical breast pain--some observations and the difficulties in treatment. AB - This paper describes a retrospective study of the clinical aspects and treatment of 566 women with cyclical breast pain over a seven-year period. Figures for the effectiveness of simple treatments including some homeopathic drugs are reported. The article concludes that reassurance is the fundamental treatment. Good responses are obtained from simple and safe drugs (oil of evening primrose, vitamin B6) with minimal side-effects. The use of stronger hormone drugs such as tamoxifen and danazol was only necessary in a small proportion of patients and resulted in a higher incidence of side-effects. PMID- 1286013 TI - Peripheral arterial thrombosis related to commercial airline flights: another manifestation of the economy class syndrome. AB - Venous thromboembolism is a well recognised complication of air travel, particularly on long haul flights. This has been attributed to relative immobility in cramped surroundings and to dehydration secondary to alcohol consumption and low cabin humidity. Under these conditions thrombosis at other sites would be expected, and indeed myocardial ischaemia is the commonest emergency in commercial flights. Peripheral arterial thrombosis, however, is not reported, even in comprehensive reviews of flying related medical emergencies. We report on three patients who developed acute lower limb ischaemia following long haul air flights. PMID- 1286014 TI - Use of the Hickman catheter for central venous access in patients with haematological disorders. AB - Hickman catheters were inserted for access in the management of 70 patients with haematological disorders. Twelve patients received a second and one patient a third catheter. The resultant 16,283 catheter-day experience is reviewed. The complication rate was 0.28 per 100 catheter days. Sepsis in the form of catheter related septicaemia (CRS) and exit site infection was responsible for 72% of complications. Staphylococcus epidermidis was the commonest organism isolated from cases of CRS. Patients receiving broad spectrum antibiotics on the day of catheter insertion were significantly less prone to catheter failure due to CRS or exit site infection (P = 0.008). The Hickman catheter is a useful and reliable method of maintaining central venous access, but prospective randomised trials are required to evaluate the role of prophylactic antibiotics in reducing the incidence of CRS. PMID- 1286015 TI - The incidence of delayed pneumothorax as a complication of subclavian vein catheterisation. AB - Delayed pneumothorax after subclavian vein catheterisation is a poorly recognised complication which can result hours or days after the catheter placement. We present our experience, during a three-year prospective study of 318 patients with 343 catheter placements in the subclavian vein. Seven patients (2.2%) developed pneumothorax immediately after the subclavian vein catheterisation. Two patients (0.6%) developed delayed asymptomatic pneumothorax that was recognised 48 and 72 hours after the catheter placement. The importance of recognition and treatment of this complication is obvious in patients with a central venous catheter, especially when they are to be operated under general anaesthesia and/or mechanical respiratory support. PMID- 1286016 TI - The selective use of fine catheter peritoneal cytology and laparoscopy reduces the unnecessary appendicectomy rate. AB - The effect of a management protocol incorporating the selective use of fine catheter peritoneal cytology (FCPC) and laparoscopy on the unnecessary appendicectomy rate was studied in adult patients (> or = 16 years) treated at one district general hospital over an 11-month period. Appendicectomy was performed on 62 adult patients managed according to this protocol, six (10%) of whom had a histologically normal appendix and no other acute condition requiring surgery. A further 57 patients underwent appendicectomy after standard clinical assessment and investigation without the use of FCPC or laparoscopy. Nineteen (33%) of these patients had a histologically normal appendix removed, with no other acute condition requiring surgical treatment. The selective use of FCPC and laparoscopy significantly reduced the unnecessary appendicectomy rate from 33% to 10% (chi 2 = 10.0, P < 0.005). The more widespread use of these techniques in patients with suspected appendicitis is therefore recommended. PMID- 1286017 TI - Nicotinamide treatment in subjects at high risk of developing IDDM improves insulin secretion. AB - Nicotinamide (NCT) has been shown to be effective in preventing the onset of type 1 diabetes mellitus (IDDM) in mice with non-obese diabetic (NOD) and beta cell damage, mediated by the diabetogenic agents including streptozotocin. NCT therapy in man has been shown to have a beneficial effect on the remission phase of IDDM, and its use is safe. In this open pilot trial we therefore studied the effect of oral NCT administration on insulin secretion rate and islet-cell antibody (ICA) titres in IDDM high risk subjects. NCT (25 mg/10 kg bw) was administered in 6/13 high risk patients identified by a family screening programme. Those subjects tested after eight months without treatment showed a decreasing secretion in comparison to onset baseline (56,1 +/- 37.8 versus 35,5 +/- 12.2), whereas the treated subjects showed an increasing insulin secretion after treatment (26 +/- 10 versus 50.2 +/- 26.6), in spite of ICA persistence. Statistical analysis shows an increased insulin secretion in the treated group versus the untreated group (chi 2 = 3.899, P = 0.048). No side-effects were observed. We conclude that NCT may repair beta-cell function in high risk subjects too if damage is not too severe; furthermore, the effect seems not to be mediated by an immune mechanism. PMID- 1286018 TI - Acute gastroenteritis: effect on nutritional status. AB - Anthropometric measurements were performed on admission and at four weeks post discharge on 25 adults referred to hospital with acute gastroenteritis. There was a significant change in weight (P < 0.001) and mid-arm circumference (P < 0.05), but no change in skinfold thickness, arm muscle area or arm fat area. The results suggest that weight change during acute gastroenteritis is more a consequence of dehydration than of malnutrition. PMID- 1286019 TI - Patient satisfaction in an urban accident and emergency department. AB - The aim of this study was to assess patients' opinions about their experience of attending an urban Accident and Emergency department. They were given a questionnaire designed to demonstrate any shortcomings in the delivery of care which required corrective actions. Just over half (50.8%) the patients responded, 411 (95%) of whom recorded satisfaction with the outcome of their visit (P = 0.0001). There was significant correlation between patient satisfaction and waiting time to see the doctor (P = 0.003), the doctor's explanation about management (P = 0.02), and total time spent in the department (P = 0.01). A total of 120 patients (27.8%) did not receive any explanation from the nurse about what was going to happen, and 267 (61.6%) received no information about possible delay. These factors did not significantly influence patients' satisfaction with the outcome, but they need to be addressed as they will obviously lead to an improved service. PMID- 1286020 TI - Too many rectal examinations? A survey of nursing management of constipation in elderly patients. AB - A survey of nursing practices for the diagnosis and management of constipation in elderly patients in a Department of Medicine for the Elderly showed that up to 100 patients each week were subjected to unsupervised digital rectal examination. This procedure may be distressing to the patients and is probably unnecessary. We question whether this is acceptable or desirable practice. PMID- 1286021 TI - Fine needle aspiration cytology of palpable breast lesions. AB - Fine needle aspiration cytology is a safe diagnostic technique for breast cancer and can identify certain benign lesions, which can be excised without affecting surrounding tissue. The combination of experienced operator and cytologist can yield high sensitivity and specificity, together with important prognostic information. PMID- 1286022 TI - Prophylactic drainage of cholecystectomy: analysis of current views. AB - Despite extensive literature on the merits of prophylactic drainage of cholecystectomy this issue remains extremely controversial. According to tradition most surgeons feel safer placing a drain either routinely or selectively in the gallbladder fossa. On the other hand, some surgeons do not employ drainage at all and even advise against it. If the data in the literature is carefully and critically analysed, no superiority of a particular practice can be concluded with certainty; however, conclusions are often misleading as they usually reflect opinions rather than facts based on data. This article does not attempt to condemn drainage or non-drainage, but rather draws attention to the fact that opinions in this respect have been largely based on equivocal data or invalid conclusions. PMID- 1286023 TI - Autologous blood transfusion today. AB - Autologous blood transfusion--the transfusion to a patient of his or her own blood--is increasingly being recognised as a useful adjunct to traditional transfusion practice. The reasons include fears of disease transmission, the potential adverse effects on the recipient's immune system of transfused donor blood, and logistical factors. The three main techniques of autologous transfusion are: (i) pre-deposit, in which patients donate blood over a period of time in preparation for elective surgery; (ii) pre-operative isovolaemic haemodilution, in which blood is removed immediately before surgery and volume replacement is given, the blood being reinfused post-operatively; and (iii) salvage transfusion--the collection of blood shed at surgery or in similar circumstances, which is reinfused immediately or after concentration and purification. All three techniques can help to improve the safety of transfusion and economise on scarce supplies of donor blood. PMID- 1286024 TI - Babington's syndrome--setting the record straight. AB - Mrs FM walked slowly to Guys Hospital on 5th July 1945. She had to walk slowly, for she had been increasingly breathless with exertion of late. She was to attend Ear, Nose and Throat Outpatients, and after some initial delays she was ushered in to see the consultant, Mr TB Layton. He had been appointed to the staff of Guys Hospital in 1912. He then served in the Great War, was twice mentioned in dispatches, and won the DSO. He claimed to be the first British officer to enter Jerusalem when it was taken by Allenby's forces. In a word he was a character; and much loved (Figure 1). PMID- 1286025 TI - The value of serological tests for syphilis in atypical genital ulcer disease. AB - A 45-year-old heterosexual man presented with phimosis three weeks after arriving in this country from India. Examination under anaesthesia and circumcision revealed a large ulcer on the ventral aspect of the penis around the fraenum. Histopathological examination of a biopsy taken from the ulcer revealed granulation tissue with inflammatory cell infiltrate. Specific and non-specific serological tests for syphilis carried out four weeks after the initial presentation showed high titres. The importance of serological tests for syphilis in genital ulcer disease, especially in atypical presentations, is discussed. PMID- 1286026 TI - Unsuspected factors in 'self-limiting' ailments. AB - An unsuspected subtotally perforated eardrum treated with wax softening drops shows how clinical findings do not always correlate with symptoms or history. Attention is drawn to the dilemma posed by delegating matters such as diagnosis and prescribing which have been considered to be purely in the medical sphere. PMID- 1286027 TI - Steatorrhoea and sub-total villous atrophy complicating mefenamic acid therapy. AB - We report a case of steatorrhoea and sub-total villous atrophy, occurring during therapy with mefenamic acid. The patient recovered on cessation of the drug while continuing a normal diet. PMID- 1286028 TI - Ileal haemangiopericytoma and von Recklinghausen's disease. AB - Haemangiopericytoma is an uncommon tumour of vascular pericytes which usually arises in deep subcutaneous tissues or the retroperitoneum. There are few reports in the English literature of haemangiopericytoma arising in the ileum. Von Recklinghausen's disease, a condition of autosomal dominant inheritance with a prevalence of 1 in 3000, is often associated with tumours of neural origin. Tumours of non-neural origin also occur in Von Recklinghausen's disease but haemangiopericytoma has not been described. We report on a patient with Von Recklinghausen's disease presenting with massive haemorrhage from an ileal haemangiopericytoma. PMID- 1286029 TI - An unusual presentation of polymyalgia rheumatica with severe muscle weakness. AB - An 83-year-old woman suddenly developed profound weakness of proximal and distal muscles in both upper limbs. Electromyography revealed abnormal changes but serum creatine kinase was normal. The weakness responded dramatically to steroid therapy. These unusual features of polymyalgia rheumatica are discussed. PMID- 1286030 TI - Dressler's syndrome presenting as acute pneumonitis. AB - An elderly man developed acute pneumonitis three weeks after a myocardial infarction treated with streptokinase. The differential diagnoses are discussed and a short review of lung disease in the post-myocardial infarction syndrome is presented. PMID- 1286031 TI - Malignant melanoma of the parotid gland. AB - We report a case which demonstrates pitfalls in the management of a parotid gland mass and highlights behaviour of malignant melanoma that is not widely appreciated. The danger of assuming a benign histological diagnosis of such a mass and the subsequent delay of definitive surgery is demonstrated. Metastases within the parotid gland are not uncommon, melanoma being one of the commonest sources. A search should always be made for a primary tumour in the head, neck and chest. This can be made exceptionally difficult by the uncommon phenomenon of spontaneous regression of the primary melanoma. PMID- 1286032 TI - The fruits of organization. PMID- 1286033 TI - Impact of biologically closed electric circuits (BCEC) on structure and function. AB - The basis of our physical world is electrical. The unified Electromagnetic field can appear to us as particles, i.e., matter, at certain densities of wavelengths. A close interrelation therefore exists between matter and electric energy. This knowledge is extensively utilized in technology. Various tools and instruments are electrically powered, utilizing the exceedingly important principle of closed electric circuits. Corresponding closed electric circuits and functions also exist in biology but are more sophisticated and complex. Unfortunately, these aspects are almost unrecognized. The principle of Biologically Closed Electric Circuits (BCEC) and some of their structural and functional effects are described. The Vascular-Interstitial Closed Circuit (VICC) is one specific BCEC system. It functions as a circulatory system in addition to the mechanical circulation. Its efficiency partly depends on its capacity to provide bidirectional transport of ions. The VICC is an in vivo electrophoretic dielectrophoretic system that is powered by metabolic energy or injury currents. A VICC activation leads to transports of metabolites, new structuring and healing of an injured tissue. Examples are also presented of the process of healing. An abnormal, e.g., prolonged activation of VICC may also induce pathology. Neoplastic formation of cells and tissue can also be healed by the use of artificially applied electrophoresis or an artificially applied electric field as will be described. Our world once developed from electrical energy. This is probably the reason why the BCEC systems make primary differences between nonbiological and biological matter. PMID- 1286035 TI - Van Gogh and the life chart. AB - Adolf Meyer originally devised the life chart in order to chronologically document a person's major life events and significant illness experiences over his or her life span. It is the purpose of this report to update Meyer's life chart through the presentation of the life events and illnesses of the famous artist Vincent Van Gogh. Van Gogh's life illustrates significant early (predisposing) life stresses, as well as clusterings of stressful (precipitating) life events occurring proximal to the occurrence of his several illnesses. Through the use of a life chart an understanding of why an individual becomes ill at a particular time in their life is enlarged. In addition, a systematic basis for formulating prognosis becomes available. PMID- 1286034 TI - Low-dimensional chaos maps learning in a model neuropil (olfactory bulb). AB - Quantification of a chaotic system can be made by calculating the correlation dimension (D2) of the data that the system generates (Packard et al., 1980). The D2 algorithm, however, requires stationarity of the generator, a feature that biological data rarely reflect (Mayer-Kress et al., 1988). So we developed the "point correlation dimension" (PD2), an algorithm that accurately tracks D2 in linked data of different dimensions (Carpeggiani et al., 1991). We now present a mathematical argument that, for stationary data, individual PD2s converge to D2 and we demonstrate that the algorithm rejects contributions made by bursts of noise. Data were obtained from the surface of the olfactory bulb of the conscious rabbit (64 electrodes, 640 Hz each, 1.3 sec epochs) before and after presentation of a novel or habituated odor. D2 could be calculated in only 1 of 10 novel-odor trials, whereas PD2 could be calculated in all. Both algorithms indicated that a novel odor evokes a spatially uniform dimensional increase. The PD2 uniquely exhibited the dimensional decreases that occur during inspiration and the gradients of mean dimension present during the nonstimulated control state. These control gradients remained unchanged without odor experience, but showed spatially specific PD2 increases following odor habituation. It is interpreted that, 1) the PD2 is sensitive, accurate, and appropriate for dimensional assessment of biological data, 2) that during analysis of unfamiliar information a single global process is transiently evoked in the neuropil, and 3) after experience multiple spatially specific processes tonically map the sites of learning. PMID- 1286036 TI - Confessions of a neobehaviorist. PMID- 1286037 TI - Reflections on human Pavlovian decelerative heart-rate conditioning with negative tilt as US: alternative approaches. AB - The negative-tilt preparation that has been reported since the late seventies is a specific form of Pavlovian conditioning that is of scientific interest and has potential applications. In this paper I reflect on the usefulness, to the development of this preparation, of two approaches to Pavlovian conditioning. One approach is the older S-R learning, stimulus-substitution paradigm exemplified by learning texts of the sixties. The other is the modern, Tolman-like view, according to which the phenomenon of Pavlovian conditioning is "now described as the learning of relations among events so as to allow the organism to represent its environment." The three assumptions encapsulated by this approach are: (a) that only CS-US contingency relations are learned; (b) that teleological modes of explanations are adequate; (c) that the representational theory of knowledge is sound. Concerning Pavlovian conditioning in general, questions been raised in the literature for all three assumptions; they have not been adequately answered. Regarding the specific problem of developing the human Pavlovian heart-rate decelerative conditioning with negative tilt as the US, I suggest that the cognitive approach has been much less helpful than the older, S-R, stimulus substitution paradigm. Nevertheless, other literature clearly indicates that the cognitive, S-S approach has generated considerable interest and research, especially in preparations like the conditioned emotional response (CER), which are CS-IR ones in the sense that the effects on the CR are assessed indirectly through measuring an indicator or instrumental response (IR).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286038 TI - Extinction instead of incubation following classical aversive conditioning in dogs. AB - Two dogs received a single paired classical conditioning trial, with tone CS and 12 mA shock US. Both dogs then showed a conditioned blood pressure increase in response to the nonreinforced CS, which extinguished with additional nonreinforced presentations. The CR showed spontaneous recovery four days later, but reextinguished with additional nonreinforced presentations. The results were interpreted as not supporting Eysenck's theory of "incubation" following one trial aversive conditioning. PMID- 1286039 TI - Conditional reflexes as related to hypnosis and hypnotic techniques. AB - Hypnosis has never been adequately explained in terms of conceptual framework of most schools of psychotherapy. The psychoanalytic concept that it consists of submission and surrender of important ego functions to the therapist does not explain all observed facts. During my wartime studies and since, I have been impressed by the observation that the patient's ego is by no means powerless and defenseless, even during a deep state of trance, i.e., in states of trance sufficiently deep to eliminate awareness of painful body injuries (1965). Erickson (1954) has shown on many occasions that in resistant subjects one of the best ways to induce trance is to encourage the patient to resist as much as he can. Haley (1963) has pointed out in detail that at the beginning of any hypnotic relationship there evolves a subtle battle for "one-upmanship." These observations certainly show that surrender in the psychological sense is by no means an aspect of even the most successfully induced trance states. PMID- 1286040 TI - Cancer research in central Europe: living under a bubble. PMID- 1286042 TI - Combined-modality therapy in the treatment of local-regional esophageal cancer. PMID- 1286041 TI - Nutrition and cancer: background and rationale of the European Prospective Investigation into Cancer and Nutrition (EPIC). AB - The development of epidemiological research on diet and cancer during the last decades is discussed. Apart from some consistent data on the protection against several cancers conferred by a diet rich in fruits and vegetables, the results provided by retrospective case-control studies on diet and cancer remain contradictory on many important issues, and primarily on the relation between diet and breast cancer. The rationale is presented for setting up large prospective cohort studies combining epidemiological and laboratory methods in order to expand the presently limited knowledge of the role of nutrition and related factors in cancer etiology. The main features of the European Prospective Investigation into Cancer and Nutrition are outlined. The study is being carried out in seven European countries and it will collect data on diet, other lifestyle and environmental factors, anthropometry as well as biological samples in a cohort of about 400,000 healthy European adults. The subjects will be followed up to investigate the incidence of and mortality from cancer in relation to epidemiological data and biochemical markers. PMID- 1286043 TI - Adjuvant therapy of primary breast cancer. 4th International Conference on Adjuvant Therapy of Primary Breast Cancer St. Gallen, Switzerland. PMID- 1286044 TI - Chemotherapy-induced anemia in patients with primary lung cancer. AB - To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05). PMID- 1286045 TI - A combination of mitoxantrone, etoposide and prednisone in elderly patients with non-Hodgkin's lymphoma. AB - From January 1988 to December 1991, 55 elderly patients (14 pretreated and 41 previously untreated) with non-Hodgkin's lymphoma (NHL) entered a prospective study to evaluate the feasibility of a combination of mitoxantrone (7-9 mg/m2), VP 16-213 (150 mg, 2-hour infusion on day 1, and 200 mg per os on days 3 and 5) and low-dose prednisone (25 mg days 1-5) (MVP regimen), recycling every 21-28 days. The median age was 75 (range 64-93). All but 4 pretreated patients had intermediate- or high-grade lymphomas. Complete remissions were obtained in 22 of 40 (55%) evaluable previously untreated patients, and partial remissions in 10 (2 of these obtained complete remissions after radiotherapy), for an overall response rate of 80%. The median duration of response was 12 months. At 24 months the overall survival was 52% and the relapse-free survival was 31%. Of 14 pretreated patients complete remissions were obtained in 4 (29%) and partial remissions in 3. Granulocytopenia and fever were the most important side effects; two patients contracted bronchopneumonia and one of them died. Other toxicities were mild. We conclude that this combination chemotherapy is effective as first line and salvage treatment in elderly patients with intermediate- and high-grade NHL, and that it is feasible on an outpatient basis, with manageable toxicity. PMID- 1286046 TI - Adult lymphoblastic lymphoma: high incidence of central nervous system relapse in patients treated with the Stanford University protocol. AB - Twelve adult patients with non-leukaemic lymphoblastic lymphoma were treated with combination chemotherapy and central nervous system prophylaxis according to the protocol developed at Stanford University. Despite strict adherence to the Stanford protocol, 4 of 12 patients relapsed in the CNS, all with meningeal disease. Only four of the 12 patients are in continuing complete remission 6 to 88 months from the completion of induction therapy. These results are inferior to those previously reported for this regimen, and fail to confirm the high rate of control of CNS disease. PMID- 1286047 TI - Prospective study with combined low-dose chemotherapy and zidovudine in 37 patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma. French-Italian Cooperative Study Group. AB - The French-Italian Cooperative Study Group included patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma (NHL), defined as those with performance status (PS) > or = 3 and/or opportunistic infections (OI), in a prospective study with a 50% reduced-dose combination chemotherapy regimen: CHVmP-Vincristine-bleo (cyclophosphamide 300 mg/m2 i.v. day 1, doxorubicin 25 mg/m2 i.v. day 1, teniposide 30 mg/m2 i.v. day 1, prednisone 20 mg/m2 per os days 1-5, vincristine 2 mg i.v. day 15, and bleomycin 10 mg i.v. day 15), given every 21 days for eight cycles, and concomitant zidovudine 500 mg per os per day. The aims of this combined treatment were to reduce bone marrow toxicity and infectious complications related to chemotherapy (with a low-dose chemotherapy regimen), and to control the HIV and related infectious complications (with zidovudine therapy). Thirty-seven patients entered this prospective study. At the time of the NHL diagnosis, 41% of the patients had asymptomatic HIV infection, 27% had ARC and 32% had already had CDC-defined diagnoses of AIDS. The median CD4+ cell count was 35 mm3. Only 29 patients are evaluable for response, since 8 received only one cycle of chemotherapy. Fifteen of 29 (52%) patients obtained objective responses, with only 4 (14%) achieving complete remissions (CR) of 1, 4, 14 and 29+ months. Three (16%) CRs were achieved in 19 evaluable patients included in the study because of poor PS, and only one CR was observed in 10 evaluable patients with histories of OI, either alone or with poor PS. The most common side effect was bone marrow toxicity with 2 related toxic deaths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286048 TI - Cyclophosphamide, doxorubicin and fluorouracil (CAF) plus depo-buserelin in the treatment of premenopausal women with metastatic breast cancer. AB - A phase II study was undertaken to assess the effect of CAF plus depo-buserelin, as first-line treatment, in premenopausal women with breast cancer. Of 66 patients entered 60 are eligible and evaluable; their median age was 45, estrogen receptor (ER) was positive in 9, negative in 11 and unknown in 40. The median disease free interval (DFI) was 11 months. Metastatic sites were visceral in 14, bone in 34 and soft tissue in 37. Twenty-nine patients had metastatic disease of one site, while 31 had 2-4 sites. An objective response of 82% was documented (29 complete responders and 20 partial responders). Median time to treatment failure was 11.5 months and median survival 37 months. Most commonly encountered side effects attributable to CAF were alopecia, nausea and vomiting, leucopenia and thrombocytopenia. Side effects attributable to buserelin were hot flashes. After one cycle baseline mean serum estradiol fell from premenopausal levels to postmenopausal levels. This study showed that CAF plus buserelin is well tolerated, with a very high response rate in selected premenopausal patients with advanced breast cancer. PMID- 1286049 TI - Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa. AB - Sixteen patients received a high-dose chemotherapy regimen consisting of carboplatin (1600 mg/m2) and cyclophosphamide (6000 mg/m2) as daily two-hour infusions over four days (CC). All but two of them also received thiotepa (480 mg/m2) in eight 30-minute infusions given every 12 hours (CTC). Bone marrow and/or peripheral stem cell (PSC) reinfusions took place 72 hours after the last course of chemotherapy. The major toxicity was bone marrow suppression, the duration of which was markedly reduced in the patients receiving PSC reinfusions. Non-hematological toxicity was relatively mild and consisted of nausea and vomiting, minor mucositis and skin rashes. All but one patient had mild and completely reversible elevations of serum ALAT and/or LDH levels. One patient, who had received full-dose chemotherapy despite a creatinine clearance of 56 ml/min, developed significant toxicity consisting of transient cyclophosphamide associated pancarditis, reversible neurotoxicity and partially reversible hearing loss and renal function impairment. There were no toxic deaths. In view of the high carboplatin dose, the CTC regimen may be particularly suitable for use in the salvage treatment of germ cell cancer. Since CTC causes no serious organ toxicity, further studies to determine its suitability for double or even triple transplantation programs are warranted. PMID- 1286050 TI - Etoposide (E) + epirubicin (E) + cisplatin (P) combination chemotherapy (EEP) in advanced gastric cancer: negative impact on clinical outcome. Spanish Cooperative Group for GI Tumor Therapy (T.T.D.). AB - One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy. The response rate was higher (30%) in patients on EEP than in those treated with FEM (p = 0.05). Severe leukopenia, anemia, alopecia and infection were significantly more frequent on EEP. In addition, because of its intrinsic toxicity, EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen, more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy. The median time to progression and median survival for EEP FEM were 2.08-3.4 and 4.2-7.9 months, respectively. Our data do not support the use of EEP chemotherapy in patients with AGC. PMID- 1286051 TI - Enantiomer-specific effects of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. AB - BACKGROUND AND OBJECTIVE: This investigation was designed to determine whether the effects on the cell firing rate (CFR) at the nucleus tractus solitarius (NTS) and on the cardiovascular system, which are associated with a toxic dose of bupivacaine, have an enantiomer-specific component. METHODS: Adult Sprague-Dawley rats were anesthetized with chloral hydrate, and a femoral artery and vein were cannulated. After the cranial surface was exposed, a 3-mm hole was drilled 2 mm caudal and 1.5 mm lateral with respect to lambda for placement of a 1-microns tungsten microelectrode. Cells of the NTS were located 6-6.5 mm from the brain surface, and CFR was continuously recorded. Lead II electrocardiogram and arterial blood pressure were also recorded. Twenty-four animals received either d or l-bupivacaine (2 mg/kg) in random order. RESULTS: Cell firing rates decreased from 21 +/- 13 to 0 +/- 0 impulses/second (p < 0.001) at 34 +/- 15 seconds after the injection of d-bupivacaine. Cell firing rates decreased from 22 +/- 17 to 2 +/- 4 impulses/second (p < 0.01) at 68 +/- 45 seconds after injection of l bupivacaine. In addition to the decreases in blood pressure and heart rate that were found, all animals exhibited an inversion in electrical axis beginning within 2-3 seconds after bupivacaine administration. Mild bradycardia was noted in four of the animals receiving the l-bupivacaine, whereas severe bradycardia was observed in all animals receiving d-bupivacaine. Most important, this severe bradycardia was accompanied by progressive hypotension. In addition, all animals receiving d-bupivacaine became apneic and died, whereas all animals receiving l bupivacaine continued to breathe and all but two of the animals survived. CONCLUSIONS: Data in the current report support the hypothesis that effects of bupivacaine on neurons of the NTS and on the cardiovascular system have an enantiomer-specific component. PMID- 1286052 TI - Effect of local anesthetic concentration on capillary blood flow in human skin. AB - OBJECTIVES: The objective of this study was to evaluate and compare the effect of lidocaine, mepivacaine, and bupivacaine on capillary blood flow in humans over therapeutic and subtherapeutic concentrations. METHODS: The effect of each treatment in eight unmedicated male volunteers was measured in a randomized, controlled, double-blind comparison. Each participant received subcutaneous injections (total, 14), at separate sites on the abdomen, consisting of 0.2 ml lidocaine (0.05%, 0.5%, 1%, and 2%), mepivacaine (0.05%, 0.5%, 1%, and 2%), bupivacaine (0.025%, 0.25%, 0.5%, and 0.75%), saline, or saline with epinephrine (5 micrograms/ml), and at an additional site a needle stick was performed and no injection made. Cutaneous blood flow was measured with a laser Doppler capillary perfusion monitor before and for 60 minutes after these interventions. RESULTS: The maximum increase in cutaneous blood flow was 277 +/- 141% to 511 +/- 136% (mean +/- SE) after lidocaine, 124 +/- 110% to 316 +/- 155% after mepivacaine, and 242 +/- 193% to 725 +/- 198% after bupivacaine. The increase in blood flow depended on local anesthetic concentration: low concentrations induced minimal changes, whereas higher concentrations caused great increases in cutaneous blood flow. Injection of saline or needle stick alone increased cutaneous blood flow 285 +/- 237% and 260 +/- 121%, respectively. CONCLUSIONS: Our findings indicate that the trauma of needle stick or saline injection produces a significant increase in cutaneous capillary blood flow. Injection of clinically useful concentrations of bupivacaine and lidocaine produced even greater increases in capillary blood flow, indicating a vasodilatory effect. Injection of the lowest concentrations of lidocaine and bupivacaine caused flow to increase to a magnitude similar to that after injection of saline. In contrast, clinically useful concentrations of mepivacaine do not increase capillary blood flow to a greater extent than saline, and lower concentrations tend to blunt the increase in blood flow, indicating a mild vasoconstrictor effect. PMID- 1286054 TI - Patient-controlled analgesia with epidural meperidine after elective cesarean section. AB - BACKGROUND AND OBJECTIVES: We report the first controlled analysis of the use of patient-controlled epidural meperidine. This randomized, prospective study compares the efficacy and safety of patient-controlled epidural meperidine to conventional intramuscular meperidine for the management of postoperative pain after elective cesarean delivery. METHODS: After delivery, 60 patients were randomly assigned to receive either conventional intramuscular meperidine therapy or epidural meperidine by a patient-controlled analgesia pump, which was programmed to deliver bolus doses in addition to a continuous background infusion. RESULTS: Patients in the patient-controlled epidural analgesia group used significantly less meperidine in the first 24 hours after surgery (p < 0.05) and had significantly lower visual analog pain scores (p < 0.05) from three hours postoperatively until study completion at 24 hours. Patients in the patient controlled epidural analgesia group ambulated sooner (19 +/- 7.8 versus 29.2 +/- 2.2 hours, p < 0.005) and cared for their infants earlier (4.6 +/- 0.9 versus 8.1 +/- 6.8 hours, p < 0.05) than patients receiving intramuscular meperidine. One patient developed a respiratory rate of four breaths per minute, 25 minutes after receiving 75 mg epidural meperidine in the operating room. This was treated with intravenous naloxone. No other serious side effects occurred in either group. Both groups were similar with regard to minor intraoperative and postoperative side effects. CONCLUSIONS: Patient-controlled epidural meperidine after cesarean delivery more effectively manages postoperative pain than conventional intramuscular use. The technique is preferred by both patients and nursing staff and can be used in the ward setting with appropriate organization and education. Respiratory depression, if it occurs, should present early after epidural bolus administration. PMID- 1286053 TI - Skin blood flow after intradermal injection of ropivacaine in various concentrations with and without epinephrine evaluated by laser Doppler flowmetry. AB - BACKGROUND AND OBJECTIVES: Skin blood flow changes after intradermal injection of ropivacaine in various concentrations with or without epinephrine were investigated using laser Doppler flowmetry. METHODS: Twenty-three non-smoking, healthy, young male volunteers participated. Four test sites were used on each forearm (volar surface) in a randomized, double-blind study. Recordings were made at 20, 40, 60, and 90 minutes after intradermal injection (0.1 ml, 30-gauge needle). Injections of saline and 1% lidocaine and an untreated area served as controls. In Series 1, various concentrations of ropivacaine (1%, 0.5%, 0.375%, 0.125%, and 0.063%) were injected. RESULTS: The data from this series showed a dose-response relationship: 1% ropivacaine provoked an increase in skin blood flow similar to saline; 0.5% and weaker concentrations of ropivacaine showed a reduction in flow compared to saline, this being more pronounced with the weakest solutions (0.125% and 0.063%). In Series 2, injection of 1:200,000 (5 micrograms/ml) epinephrine alone and injections of ropivacaine in various concentrations (1%, 0.5%, and 0.25%) with addition of epinephrine were carried out. Injection of epinephrine alone showed a flow almost as low as at the untreated control sites. Ropivacaine epinephrine injections were followed by a lower skin blood flow compared to saline, but the flow was significantly larger compared to the effect of epinephrine itself at the 20-minute recording. CONCLUSION: The combination of ropivacaine and adrenaline did not accentuate but instead diminished the vasoconstrictive effect of epinephrine. PMID- 1286055 TI - Distribution of 3H-morphine after lumbar epidural administration in unanesthetized rabbits. AB - BACKGROUND AND OBJECTIVES: This study focused on the distribution of 3H-morphine in the spinal cord, roots, urine, and blood, after epidural administration in rabbits. METHODS: Under nitrous oxide, halothane, and oxygen endotracheal anesthesia, the cisterna magna of New Zealand albino rabbits was cannulated for cerebrospinal fluid sampling, and catheters were placed in the lumbar epidural space. Through the epidural catheter, 200 pmol of 3H-morphine contained in 500 microliters of 1.3 mM (0.21 mg) morphine was injected. Arterial blood and cisternal CSF were sampled at 0, 5, 15, 30, 45, 60, 90, and 120 minutes after injection. Animals were killed with intravenous pentobarbital at the end of 120 minutes (n = 3), 6 hours (n = 4), and 12 hours (n = 2). In each animal the brain, spinal cord, spinal roots, liver, kidneys, and urinary bladder were removed. RESULTS: The injection site over the cord was identified and all tissues were immediately frozen at -70 degrees C. Two-mm thick cross-sections, were taken from every centimeter of the spinal cord. Radioactivity in the series of sections was determined by scintillation spectroscopy. At 2 hours, 4.2% +/- 1.1% of the injected radioactivity was recovered, and at 6 hours 1.6% +/- 0.6% was recovered. Radioactivity was concentrated mainly around the lumbar injection site, and it decreased as the distance increased from the injection site and coincided with elapsed time after the injection. CONCLUSION: Multiple linear regression analysis of radioactive labels showed the significant effect of time, distance from the injection site, and the time-distance interaction on the distribution of 3H morphine in the spinal cord (p < 0.0001 for time and rostral and caudal distance from the injection site; and p < 0.0001 for interaction between time and distance.) A major portion of the injected radioactivity was recovered in the urine and a small amount in other tissues and body fluid: bladder, liver, spinal roots, kidney, plasma, and cerebrospinal fluid. PMID- 1286056 TI - Thoracic paravertebral block in chronic postoperative pain. AB - BACKGROUND AND OBJECTIVES: Chronic postoperative pain in thoracic dermatomes is common. The most frequently used methods of pain relief in this area are posterior multidermatomal intercostal nerve or thoracic epidural blocks. Compared with these methods, thoracic paravertebral block may have some advantages. Usually only one injection is needed, and the use of larger volumes of local anesthetic (up to 25 ml) results in widespread unilateral analgesia including sympathetic block without the potential risk of hypotension and motor block associated with epidural block. METHODS: We retrospectively analyzed 281 thoracic paravertebral blocks performed for chronic postoperative pain (post-thoracotomy and postmastectomy) from 1986 to 1990 in our pain clinic. RESULTS: In post thoracotomy group, patients were without pain for at least a month after 58% of the blocks; in 30%, the effect lasted for at least two months; in 8%, more than four months and, in 3%, more than five months. In 88% of patients with postmastectomy pain, the achieved pain relief with thoracic paravertebral block was less than a month. No severe complications occurred. CONCLUSIONS: Thoracic paravertebral block proved to be a reliable and safe technique for unilateral pain relief in chronic post-thoracotomy pain. PMID- 1286057 TI - When to remove an epidural catheter in a parturient with disseminated intravascular coagulation. AB - BACKGROUND AND OBJECTIVES: Pain from labor and delivery is often attenuated with epidural anesthesia. A complication of indwelling epidural catheters is intraspinal hematoma. The development of a bleeding diathesis can worsen complications markedly. CONCLUSIONS: Frequent assessment of neurologic status is important until the underlying cause of the coagulopathy can be treated and the bleeding resolves. If there is no indication of intraspinal bleeding, we recommend removing the catheter because of potential catheter migration. If bleeding is occurring around the catheter insertion site and possibly in the epidural or subarachnoid space, the catheter may be left in place to tamponade the insertion site. In cases of intraspinal hematoma, which can cause neurologic deficits, immediate decompression surgery is needed. PMID- 1286058 TI - Osteitis condensans ilii misdiagnosed as post-epidural block backache. PMID- 1286059 TI - Cauda equina syndrome, continuous spinal anesthesia and repeated spinal block. Is there a relationship? PMID- 1286060 TI - Self-reactive T cells are present in the peripheral lymphoid tissues of cyclosporin A-treated mice. AB - Cyclosporin A (CsA) prevents most immature thymocytes from progressing to a mature phenotype and blocks the deletion of T cells that express self-specific TCR in the small population of cells that achieve maturity. The latter effect may explain the paradoxical observation that this immunosuppressive drug can induce autoimmunity in irradiated rodents and humans if administered while new T cells are developing in the thymus. This study shows that the repopulation of the periphery with mature T cells is delayed in irradiated CsA-treated mice, presumably because CsA blocks T cell development in the thymus. The peripheral repertoire of these mice contained self-reactive IL-2 producing T cells that could be detected in a sensitive limiting dilution assay. In addition, self reactive T cell hybridomas were isolated from the IL-2 receptor+ population present in CsA-treated mice. One of these hybridomas expressed a TCR V beta chain that is normally expressed on thymocytes that are deleted via recognition of self antigens. Despite the presence of self-reactive T cells that had escaped clonal deletion, CsA-treated mice rarely developed lethal autoimmune disease, implying that a peripheral mechanism of tolerance can prevent the onset of autoimmune disease. PMID- 1286061 TI - Activation of B lymphocytes by NK cells. AB - The ability of NK cells to induce differentiation of B lymphocytes to IgM secretion in vitro has been investigated. Homogeneous preparations of NK cells obtained from IL-2 propagated splenocytes from SCID mice were found to have the ability to induce resting B lymphocytes to proliferate and secrete significant amounts of IgM. The induction is greatly enhanced by the presence of both IL-2 and IL-5 and does not require T lymphocytes or adherent cells in the responding population. Cell contact between the two populations is not necessary suggesting that the effect is mediated by soluble factor(s) which can be produced even by irradiated NK cells. Because the activity cannot be replaced by either r-tau-IFN or tumor necrosis factor-alpha or inhibited by antibodies to these lymphokines, a novel NK cell-derived factor(s) may be involved. The implications of this interaction between NK cells and B lymphocytes are discussed. PMID- 1286062 TI - Interleukin 10 inhibits allogeneic proliferative and cytotoxic T cell responses generated in primary mixed lymphocyte cultures. AB - The effects of IL-10 on the generation of alloreactivity in primary mixed lymphocyte cultures (MLCs) were investigated. IL-10 inhibited in a dose-dependent fashion the alloantigen-induced proliferative responses. The suppressive effect was maximal when IL-10 was added at the beginning of the cultures, suggesting that it acts on the early stages of T cell activation. The proliferative responses were enhanced in the presence of a neutralizing anti-IL-10 mAb, indicating that endogenously produced IL-10 suppresses proliferation in primary MLC. The inhibitory effects of IL-10 were observed irrespective of whether irradiated allogeneic peripheral blood mononuclear cells, purified monocytes or freshly isolated B cells were used as stimulator cells. The proliferation of both the CD4+ and CD8+ T cell subsets was inhibited to a similar extent. The reduced proliferative responses were only minimally restored by high concentrations of exogenous IL-2, indicating that the effects of IL-10 are not exclusively due to inhibition of IL-2 synthesis. Furthermore, the production of IL-2, interferon (IFN)-gamma, IL-6, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-alpha in primary MLCs was diminished by IL-10 and enhanced in the presence of anti-IL-10 mAb. The strongest effects were observed on the production of IFN-gamma. Although IL-10 reduces the proliferative responses, the ratios of CD3+CD4+ and CD3+CD8+ T cells remained the same in IL-10 treated and control cultures, yet the percentages of activated CD3+ T cells, as judged by CD25 and HLA-DR expression, were consistently reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286063 TI - Identification of single amino acid substitutions in the staphylococcal nuclease protein that enhance and diminish T cell clone recognition of naturally processed peptides. AB - It has been inferred that residue changes that affect T cell recognition of synthetic peptides will have a similar effect in the intact protein. However, since small peptides do not require antigen processing it is possible that residue changes in synthetic peptides will not have an equivalent effect in the intact protein. Mutant proteins of staphylococcal nuclease (Nase) and 15mer synthetic peptides with corresponding substitutions were compared to determine if residue changes within an immunodominant epitope have an effect on the generation of naturally processed peptides. Five different substitutions in the synthetic peptide resulted in loss of reactivity of individual Nase-specific clones. When the same single amino acid changes were made in the intact protein, the naturally processed peptides were also unable to stimulate the Nase-specific clones. However, two other substitutions in the synthetic peptide were stimulatory for a T cell clone even though the same changes in the intact protein were non stimulatory. These results suggest that certain residue changes affect recognition of the naturally processed peptide but not the synthetic peptide with the same amino acid change. In addition, these results demonstrate that the effects of amino acid substitutions in synthetic peptides on T cell recognition may not always reflect the effects of these substitutions in the intact protein. Substitutions located outside Nase-specific T cell epitopes were also examined. Thirty different mutant proteins were all stimulatory. Moreover, a number of these mutants proteins were 50- to 100-fold more efficient in their stimulatory capacity than the native Nase protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286064 TI - Induction of protective CD8+ T lymphocytes by an attenuated Listeria monocytogenes actA mutant. AB - We tested the ability of an attenuated actA mutant of Listeria monocytogenes to induce protective immunity in mice. This mutant can enter and multiply in the cytosol of the infected host cell, but is deficient in actin-dependent cell-to cell spread. It was found to be of attenuated virulence for inbred C3H mice: the LD50 after i.v. injection was 1000-fold higher than that of the wild-type strain. Mutant bacteria multiplied up to the fourth day in the liver, but only for 1 day in the spleen. A single infection with the maximum sublethal dose of the actA mutant induced long-lasting immunity; the LD50 of virulent wild-type L. monocytogenes increased 100-fold and growth of wild-type L. monocytogenes was controlled in liver and spleen of these mice. The presence of Listeria-reactive T cells in spleen of C3H mice infected 7 days previously with the actA mutant was monitored, through their ability to protect naive syngeneic recipients against wild-type L. monocytogenes. Protection was mainly conferred by Thy-1+ CD8+ T lymphocytes; depletion of CD4+ T cells had no significant effect on the level of transferred protection. Such attenuated mutants may be used to develop live vector vaccines for delivery of heterologous proteins into the cytosol, thereby favoring the induction of a CD8+ T cell response. PMID- 1286065 TI - Threshold tolerance in H-2Kb-specific TCR transgenic mice expressing mutant H 2Kb: conversion of helper-independent to helper-dependent CTL. AB - To evaluate the role of the structure of the class I molecule and associated peptide(s) in intrathymic selection and tolerance, mice expressing as a transgene (tg) a TCR specific for the H-2Kb alloantigen were crossed with mice expressing the mutant class I molecule H-2Kbm1 or H-2Kbm8. In H-2k/k TCR tg mice (in a situation of exclusive positive selection), peripheral tg TCR expressing (Ti+) CD8+ T cells showed high, suboptimal, and an absence of reactivity for H-2Kb, H 2Kbm1, and H-2Kbm8, respectively. In the peripheral lymphoid organs of TCR tg H 2k/k, H-2k/bm8, H-2k/bm1, and H-2k/b mice respectively, the tg TCR was expressed on T cells with decreasing intensity of surface CD8. Thymic subpopulations of TCR tg mice presented a pattern of negative selection with decreasing intensity from H-2k/b to H-2k/bm1 and H-2k/bm8. This suggests that a weak interaction between the TCR and H-2Kbm8 exists which partially results in negative, but not in positive, intrathymic selection. Results further indicate that expression of H 2Kbm8 does not induce tolerance to H-2Kb. In H-2k/bm1 mice, the peripheral Ti+ CD8lo cells express two distinct types of 'threshold' tolerance in vitro: (i) they generate cytotoxic T lymphocytes (CTL), in the presence of exogenous IL-2, which fail to respond to H-2Kbm1 but remain reactive to H-2Kb; and (ii) they do not make significant titers of IL-2 and do not significantly proliferate in response to H-2Kb, unlike the Ti+ CD8+ T cells from H-2k/k TCR tg mice which respond efficiently. These results show that tolerance is induced up to a level of non-reactivity within a given MHC environment: for the same TCR, CTL reactivity to H-2Kbm1 is totally lost, whereas CTL reactivity to H-2Kb is only slightly reduced. Additionally, proliferation and IL-2 production by Ti+ CD8+ cells in response to H-2Kb were strongly affected in H-2k/bm1 mice. Thus, in H 2k/k mice the Ti+ CD8+ cells behave as helper-independent, whereas in H-2k/bm1 mice CD8+ cells expressing the same TCR behave as helper-dependent CTL. PMID- 1286066 TI - Inhibition of tumor growth by histoincompatible cells expressing interleukin-2. AB - Murine tumor cells engineered to express IL-2 have been shown to be rejected by the syngeneic host, which is then protected against a subsequent tumorigenic challenge. To assess whether IL-2 has to be produced by the tumor cells themselves, or whether its local delivery would be sufficient to promote such beneficial effects, the syngeneic tumor cells were co-inoculated with allogeneic or xenogeneic cells secreting IL-2, selected after gene transfection. In several murine systems, it was observed that this is an efficient approach for controlling the growth of the syngeneic tumor. However, animals which rejected the tumor were not protected against a subsequent challenge. Several lines of evidence indicate that NK cells play a major role in tumor rejection induced by the IL-2 expressing histoincompatible vector cells. Thus, while local delivery of IL-2 in the vicinity of a tumor might not be sufficient to promote a systemic long-term specific antitumor immune response, it can control the growth of the primary syngeneic tumor. These experiments demonstrate the feasibility of using genetically engineered histoincompatible cells (which are rejected by the host's immune system) as a transient delivery system in vivo. PMID- 1286067 TI - Treatment of burns with skin substitutes. AB - More than 2 million persons sustain thermal injuries in the United States annually (Monafo and Crabtree, 1985) and more than 10,000 burn victims die (Collini and Kealey, 1989). The principal factors affecting mortality are the total area burned and the area of third degree (full thickness) burns (Tompkins et al., 1985) with wound sepsis being the leading cause of mortality. Early aggressive excision and immediate covering of the wounds improve survival (Herndon and Parks, 1986). Various biological and synthetic substrates have been employed to replace the injured skin. Most of these provide a permeability barrier which substitutes for the epidermal function of the lost skin. An ideal skin replacement should also provide a substitute for dermis, which provides both support and stability for the epidermal replacement and prevents wound contraction. The dermal and epidermal replacement should be firmly integrated by a complete basement membrane zone (BMZ). PMID- 1286068 TI - Contact hypersensitivity reaction to ovalbumin in newborn guinea pigs from maternally sensitized animals. AB - An animal study was conducted to elucidate the role of ovalbumin (OA) in the development of eczematous lesions in intrauterine sensitized newborns. Four groups of pregnant guinea pigs were used: group A, immunized by oral administration of 1% OA in drinking water until parturition; group B, immunized by intradermal injection of OA with Freund's complete adjuvant; group C, immunized by both methods; and group D (control), not immunized. The newborn guinea pigs of each group were patch tested with 10% OA in white petrolatum. Positive reactions were seen in the newborns of groups B and C, but not in those in groups A and D. By enzyme-linked immunosorbent assay and passive cutaneous anaphylaxis, a high titre of OA-specific IgG was detected in the group B and C newborns. The number of positive patch test reactions decreased concomitantly with the decline of specific IgG. Histologically, eczematous changes were observed in the positive reaction sites. Many OA antigen-bearing Langerhans cells were found by the immuno-double labelling technique. Immuno-electron microscopic findings revealed the presence of OA antigens as well as IgG molecules on the cytoplasmic membranes of Langerhans cells. Our studies demonstrated that maternal sensitization with OA can induce an eczematous reaction in the newborns to OA patch testing under the presence of high levels of OA-specific IgG in the serum. From these findings it is suggested that IgG plays an essential role in the development of contact hypersensitivity reaction to OA. PMID- 1286069 TI - Genetic nature of vitiligo. AB - Four hundred vitiligo patients and 100 non-vitiliginous controls were studied to find out the prevalence of vitiligo in relatives of patients and controls. The difference was found to be statistically highly significant. The data reflected that there is some genetic mechanism involved in the etiology of vitiligo. Respective relatives of all forms of the disease in the vitiligo group showed a clear preponderance compared to controls. There was clustering of affected relatives in vitiligo cases compared to controls. The ratio of affected and unaffected siblings with unaffected parents or one parent affected, the ratio in the children of probands, the ratio in children of affected paternal and maternal grandparents of probands, suggest the polygenic nature of vitiligo. PMID- 1286070 TI - Malignant blue nevus: a report of eight cases. AB - Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision. PMID- 1286071 TI - Flow cytometric analysis of pig epidermal keratinocytes: effects of tape stripping. AB - Tape stripping is a dynamic in vivo model for the induction of synchronized keratinocyte proliferation. We investigated the cell kinetics of pig epidermis by DNA-flow cytometric analysis, which was compared with [3H]thymidine incorporation mitotic counts and 2-[3H]-deoxy-D-glucose uptake. The stripping was standardized and confirmed histologically by the observation of complete removal of horny layer. Following the stripping, the proportion of cells in S-phase showed no remarkable change until 12 h. This was followed by a spike-like increase in the S phase cells, the peak of which was reached at 24 h. This gradually decreased and returned to basal levels by 48 h. The cells in G2/M fraction initially decreased; the lowest value was obtained at 12 h. This was followed by a marked increase in the G2/M fraction, the peak of which was at 36 h. The keratinocytes in G2/M fraction gradually returned to basal levels by 96 h. [3H]Thymidine uptake and mitotic counts were mostly parallel with the data of the flow cytometric analysis, suggesting the latter as being a reliable system for cell kinetic analysis. The glucose uptake initially decreased (at 6 h following the stripping) and then increased at 24 h. Histologically the stripped epidermis regained its horny layer almost completely by 72 h following the stripping; this was occasionally accompanied by a moderate acanthotic change thereafter. PMID- 1286072 TI - Mathematical assessment of the spatial distribution of Langerhans cells in guinea pig epidermis. AB - Two mathematical indexes, Hopkins-Skellam index (HSI) and Morisita index (MI), were applied to assess the distribution of ATPase-stained epidermal Langerhans cells (ELC) in the guinea pig skin. To our knowledge, this is the first report in which the degree of regularity has been expressed numerically by computation based on theoretical equations. The regularity of ELC in the normal skin was confirmed by the value of HSI (P < 0.0001). In the topical steroid applied skin, the number of ELC decreased significantly but the value of HSI was similar to that of the normal skin; while in the ultraviolet B (UVB) exposed skin, both number of ELC and regularity of ELC distribution decreased significantly. The graph of MI for the UVB exposed skin clearly showed that the distribution of ELC had local clumps. The two indexes, HSI and MI have been quite useful for determining the regularity of ELC. These indexes may have a wide application to other cells. PMID- 1286073 TI - Influence of phenobarbital on ECoG phenomena induced by metrazol in rats during ontogenesis. AB - Effect of phenobarbital (PhB, 20 and/or 40 mg/kg) on epileptic ECoG phenomena induced by metrazol was studied in acute experiments in rats aged 7, 12, 18, 25 and 90 days. Fractionated administration of metrazol (20 mg/kg i.p. each 300 s) was used to quantify the effects of PhB. First signs of metrazol action (sharp elements and/or rhythmic metrazol activity) were not reliably influenced by PhB. On the contrary, the latency of the first EEG seizures as well as of the first generalized EEG seizures was prolonged and thus a dose necessary for their elicitation was increased in all age groups. These differences reached statistical significance in 12-, 18- and 25-day-old rats. A lack of effect of PhB against the rhythmic metrazol activity supports the adequacy of this activity as a model of human absences. Differences between the development of antiepileptic and hypnotic effects of PhB (described earlier) suggest two different mechanisms of action. PMID- 1286074 TI - Sensitivity of the generator of spontaneous motility in chick embryos to the acute and chronic administration of MPTP. AB - The acute and chronic effect of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) on spontaneous motor activity and its development was studied in chick embryos. 1. From the 13th day of incubation, the acute effect of MPTP (30 mg/kg e.w., up to 60 min after administration) consisted in significant depression of spontaneous motility. From the 17th day, the effect of MPTP in supraspinal compartments of the CNS also began to participate in this depression. 2. The subacute effect of MPTP (up to 24 h after a single dose) was lethal for 11-day old embryos. Conversely, in older embryos resting motility partly recovered, with signs of an inverse correlation to the embryo's age. The final effect, however, consisted in absolute failure of the hatching process 3. The chronic effect of MPTP (3.57 mg/kg e.w./24 h, from the 4th to the 16th day of incubation) led to a developmental reduction of spontaneous motor activity, chiefly from the 8th to 12th day of incubation. 4. The interaction of nialamide (25 mg/kg e.w.), a blocker of monoaminooxidase produced disparate results with the effect of MPTP in young and old embryos. PMID- 1286075 TI - Antidiuretic activity of terlipressin (triglycyl-lysine vasopressin)--role of pressure natriuresis. AB - Terlipressin (triglycyl-lysine vasopressin TP), a "hormonogen" analogue, was introduced in gastroenterology for its low and protracted vasopressor action, reducing bleeding from gastrointestinal tract. Its antidiuretic activity, estimated originally in ethanol-anaesthetized rats (Sawyer's method) was claimed to be equally low and protracted. We performed several series of antidiuretic tests on conscious rats (Burn's method) with the following results. TP in low doses of 0.05-1.0 micrograms/kg exhibited typical dose-dependent antidiuretic effect. In the dose of 0.2 micrograms/kg, the dynamics of urine and sodium excretion did not differ from that after equivalent dose of lysine vasopressin and equipotent dose of DDAVP. The antidiuretic potency of TP (estimated by parallel line assay) was 175.0 U/mg. TP in doses of 5.0 and 20.0 micrograms/kg exhibited limited diuresis and marked natriuresis. High osmolality and sodium content were present in all portions of excreted urine. The discrepancy between previous and our results concerning antidiuretic activity of TP and the role of pressure natriuresis for overall renal action of TP are discussed. PMID- 1286076 TI - Effect of cisplatin, carboplatin and stobadine on lipid peroxidation of kidney homogenate and phosphatidylcholine liposomes. AB - The effects of the nephrotoxic, anticancer agents cisplatin (CDDP) and carboplatin (CBDCA), and the free radical scavenger, stobadine, were investigated on lipid peroxidation (LPO) of rat kidney homogenates and phosphatidylcholine (PC) liposomes. Kidney homogenates were incubated in air at 37 degrees C for 6-48 h and lipid peroxidation was detected spectroscopically as absorbance (533 nm) of the thiobarbituric acid-malondialdehyde (TBA-MDA) complex. CDDP (0.3-10 mmol.l-1) increased LPO of the homogenate. CBDCA decreased the TBA-MDA absorbance, yet was found to interfere with MDA, TBA and/or with the TBA-MDA complex. Thus when CBDCA is involved, the TBA-MDA method for detection of LPO is not suitable. Stobadine (0.1 mmol.l-1 and 1 mmol.l-1) inhibited LPO either in the control homogenate and in the homogenate where peroxidation was increased by CDDP. The effect of CDDP and CBDCA on peroxidation of PC liposomes was monitored as oxygen consumption using a Clark-type oxygen electrode. CDDP increased but CBDCA decreased the rate of oxygen consumption during the peroxidation of liposomes induced by FeSO4. The results suggest that the effects of CDDP and CBDCA on LPO may be linked with their nephrotoxicity. PMID- 1286077 TI - Effect of propylthiouracil on liver regeneration in rats after partial hepatectomy. AB - The effect of propylthiouracil (PTU) on the growth activity of intact liver and liver regenerating after partial (65-70%) hepatectomy (PH) was studied in rats. PTU (Propycil, Kali-Chemie, FRG) was dissolved in drinking water (1 g PTU per litre) and this was given to the rats, as their sole source of fluids, three days before PH and then up to the end of the experiment. In rats given PTU, marked inhibition of liver DNA synthesis and the mitotic activity of hepatocytes was found after PH. This effect was potentiated to some extent by partial inanition of the experimental animals given PTU, as demonstrated in a paired feeding test in control rats. PTU inhibition of DNA synthesis in intact and regenerating liver also took effect in thyroidectomized rats, even with substitution (thyroid hormone) therapy. The experiments demonstrated that the effect of propylthiouracil on DNA synthesis in the liver is mediated primarily by way of its direct effect on the liver. PMID- 1286078 TI - Acute pneumonia reversibly inhibits hypoxic vasoconstriction in isolated rat lungs. AB - Pneumonia was induced in rats by instillation of carrageenin (0.5 ml of 0.7% solution) into the trachea. Three or four days after instillation, the lungs were isolated, perfused with blood of healthy rat blood donors, and ventilated with air + 5% CO2 or with various hypoxic gas mixtures. Pulmonary vascular reactivity to acute hypoxic challenges was significantly lower in lungs of rats with pneumonia than in lungs of controls. The relationship between O2 concentration in the inspired gas and Po2 in the blood effluent from the preparation was shifted significantly to lower Po2 in lungs with pneumonia compared to control ones. These changes were not present in rats allowed to recover for 2-3 weeks after carrageenin instillation. We suppose that blunted hypoxic pulmonary vasoconstriction may contribute to hypoxaemia during acute pulmonary inflammation. Decreased Po2 in the blood effluent from the isolated lungs with pneumonia implies significant increase of oxygen consumption by the cells involved in the inflammatory process. PMID- 1286079 TI - Effect of recombinant bovine somatotropin (somidobove) in a sustained release vehicle on plasma somatotropin level and lactational performance of dairy cows. AB - The effects of administration of recombinantly derived bovine somatotropin (somidobove) in a sustained-release vehicle on the profiles of concentrations of bovine somatotropin (bST) in the blood plasma and on the milk yield of dairy cows of three herds were examined. Cows (36-87 days post partum) were treated subcutaneously with recombinant bST at 28-day intervals. In control animals, basal concentrations of bST averaged 1.4 ng.ml-1 in first-calf heifers and 1.5 ng.ml-1 in multiparous cows. In somidobove treated first-calf heifers, the concentration of bST was increased to 10.7, 14.5, and 27.0 ng.ml-1 at 24 h postinjection and in multiparous cows to 6.6, 11.0, and 11.7 ng.ml-1 on day 2 postinjection of 320, 640, and 960 mg of somidobove, respectively. On day 8 postinjection the average plasma bST levels of both parity groups are similar (on the average 3.4, 8.6, and 12.5 ng.ml-1 for three doses of somidobove respectively) and for the two highest doses being still significantly increased. During the 2nd week postinjection plasma bST concentration declined returning to control levels on day 15 postinjection. Somidobove-treated first-calf heifers produced 10.9, 16.7 and 17.9% and multiparous animals 25.5, 24.2 and 32.5% more milk than the controls when given 320, 640 and 960 mg somidobove, respectively. The cyclic pattern in milk yield within each 28-day injection interval was observed consistently in all herds. The milk yield increased to a maximum between day 4 to 8 postinjection and then slowly declined. Milk composition was not affected by somidobove treatment. PMID- 1286080 TI - Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis. AB - An impairment of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of prostaglandin synthesis inhibitors (PGSIs), indomethacin or diclofenac, was observed. Morphological examination of the gastrointestinal tract and the estimation of blood loss into its lumen in animals treated with diclofenac did not show serious damage such as haemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation. PMID- 1286081 TI - Effect of acute alcohol treatment on dopamine concentration in corpus striatum of rats: a voltammetric study. AB - A voltammetry technique has been used to determine changes in dopamine release in the rat corpus striatum after two doses of ethanol administration. The dopamine oxidation current reached a maximal value at 30 min after the first alcohol dose with a subsequent decrease towards the initial level at 60 min and kept to the basal level with a statistically insignificant oscillation. When a second dose of alcohol was applied at 60 min, it was followed by a decrease of the dopamine oxidation current peak to 50% of the initial value after another 60 min observation. The results resemble the known effect of alcohol on human behaviour (excitation followed by depression). PMID- 1286082 TI - Effects of clonazepam on picrotoxin-induced convulsions. AB - The convulsant effects of four doses of picrotoxin (PX)-2, 3, 4, and 6 mg/kg s.c. were evaluated in the first part of the study. The 4-mg/kg dose, which elicited minimal seizures in all animals, generalized tonic-clonic (major) seizures in 75% of rats and fatal outcome in 69% of rats, was chosen for the second part, i.e. for testing the anticonvulsant action of clonazepam (Rivotril Roche, 0.1 or 1 mg/kg i.p.). Clonazepam exhibited a dose-dependent action against PX-induced seizures, being more efficient against major than against minimal seizures. PMID- 1286083 TI - Morphometric analysis of coated vesicles in developing rat muscle spindles. AB - The incidence of coated vesicles under sarcolemmal surfaces of equatorial, juxta equatorial and polar regions in developing and adult spindles of the rat soleus muscle was examined by quantitative morphometry of transverse ultrathin sections. Coated vesicles were more numerous: 1) under primary sensory endings than under other types of neuromuscular contacts; 2) under the appositional sarcolemma between neighbouring intrafusal fibres than under free surfaces of the sarcolemma; and 3) in developing than in mature spindles. Factors such as location and age of the animal often interacted to produce an additive effect on the incidence of coated vesicles. Although there was a high incidence of coated vesicles at the postsynaptic surface under sensory terminals of bag2 fibres in 18 and 19 day gestational embryonic rats, it peaked in 4 day postnatal animals. The high incidence of coated vesicles at sensory endings supports the view that coated vesicles mediate neurotrophic interactions between afferents and intrafusal fibres during the critical late gestation and early postnatal time period, as sensory axons first contact their target fibres and exert a maximal directing influence on the differentiation of intrafusal fibre types. In addition, the preferential localization of coated vesicles under appositional rather than free surfaces of developing intrafusal fibres in 0-4 day rats suggests that they play a role in the transport of active substances among intrafusal fibres exhibiting different stages of maturity. PMID- 1286084 TI - Voltammetrically determined differences in changes evoked by KCl microinjections on catecholamine levels in the reticular formation and corpus striatum of the rat. AB - Using a microelectrode with carbon filaments and the voltammetric technique, changes evoked in the catechol oxidation current (CA.OC) and multiple unit activity (MUA) by microinjection of 3-5 microliters 0.5 mol.l-1 KCl were studied in the reticular formation (RF) of the medulla oblongata of anaesthetized rats; the effect of KCl stimulation of the RF and corpus striatum (S) on the CA.OC in these structures was compared. The microinjection of KCl in the vicinity of the working electrode in the RF caused depression of MUA which began 2-3 s after administration, persisted for up to 6 min after and then diminished, reaching control values within 9 min. The voltammetric signal was first recorded in the 1st min after microinjection, when there was an evident decrease in the CA.OC value (59% of the control value); this effect reached its maximum 7 min after administration (a mean drop to 23% of the control), while at the end of the experiment (i.e. after 24 min) CA.OC values had risen to 45-80% of the control value. The response in the S had a biphasic character, however. Immediately after the microinjection (1st min), the mean CA.OC value rose to 626% of the control, while in the second phase (3-10 min) it was seen to fall below the control values (means 21-63% of the control). The differences in the changes evoked by K+ depolarization in the concentration of catecholamines in the RF and S microenvironment are discussed from the aspect of the existence of different pools of the transmitter and other regional differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286085 TI - Vestibular system galvanization in man: the effect of stimulation field changes on the angle of body mass centre displacement. AB - During monopolar monoaural galvanization the absolute value of body mass centre displacement angle did not depend on the stimulation electrode position. The angle value was always close either to 0 degrees or to 180 degrees (i.e. in the latero-lateral direction). However, some fine angle differences between different electrode positions occurred and they were statistically significant in two cases. During monoaural bipolar stimulation the body mass centre moved practically in all directions (for all four used electrode positions) and the angles formed a more or less coherent rosette in the range of 0 degrees-360 degrees. PMID- 1286086 TI - Different degrees of lipid peroxidation in the CNS of young and adult rats exposed to short-term hypobaric hypoxia. AB - The authors studied the effect of short-term (20 min) hypobaric hypoxia at simulated altitudes of 7000 and 9000 m on the peroxidation of lipids in the cerebral cortex, subcortical formations, medulla oblongata and cerebellum of the laboratory rat. In 5- and 21-day-old rats, increased lipoperoxidation was recorded in all the studied regions of the brain. Differences were observed in sensitivity to the degree of hypoxia. In 5-day-old rats the response to both exposures was the same, but in 21-day-old animals exposure at 7000 m stimulated peroxidation in the cerebral cortex only (at 9000 m in all the parts of the CNS examined). In 35-day-old and adult rats, changes in the malondialdehyde concentration were likewise found after exposure at 9000 m, but not in every compartment (in 35-day-old rats in the cerebral cortex and subcortical formations and in adult rats in the cerebral cortex). In young rats, 30 and 60 min after exposure to hypoxia the malondialdehyde concentration was still higher than in older animals. PMID- 1286087 TI - Transformation of blood monocytes to multinucleated giant cells in vitro: are there any differences between malignant and nonmalignant states? AB - Blood monocytes (BMs) from 139 subjects (70 malignant melanoma patients, 31 breast cancer patients, 38 healthy controls) were cultured for at least 7 days. The formation of multinucleated giant cells (MGCs), which was checked during the whole time of culture, was observed in all cases. By the seventh day MGCs represented 25-50% and during the second and third month more than 90% of all cells. Lymphokines and/or concanavalin A stimulation (16-34 cases respectively) of BMs was performed as well. This stimulation greatly accelerated MGC formation. There were no differences either in spontaneous or in stimulated fusion between the different groups compared. PMID- 1286088 TI - The human thermoregulation range within the neutral zone. AB - A mathematical and physical model of thermoregulatory mechanisms has been derived and experimental data are presented for the elements of the model. The thermoregulatory range within the neutral zone has been analyzed by regression analysis of the experimental data. The optimal globe temperature and the adaptational shifts in temperature for winter and summer are also given. PMID- 1286089 TI - Contribution to the problems of volume parameters of the left heart ventricle of patients with ischaemic heart disease. AB - The authors studied some methodological questions associated with evaluation of the X-ray of the left ventriculogram (VTG). On the basis of their results they suggest that, in addition to the usual comprehensive volume parameters of the left ventricle (EDVI, ESVI, and EF), further indices, obtained either by drawing the cardiac contour frame-by-frame (norm dV/dtmin), or by dividing the diastole into halves or thirds (the indices norm FF 1/2 or norm FF 1/3), should be used. These indices allow more sensitive differentiation of patients with impaired left ventricular function. PMID- 1286090 TI - Age dependence of the utilization of different quality proteins in animal experiments. AB - Male rats aged 45, 85, 145 and 270 days (daily body mass increments on an optimal diet containing casein were 6.73, 2.88, 0.53 and 0.31 g respectively) were fed 15 days ad libitum on a diet with a nutrient content physiological for their age, in which the protein source was milk casein (ratio of essential to nonessential amino acids E/N = 0.79, compensation coefficient K = 14) or wheat gluten (E/N = 0.30, K = -8). In the case of gluten, net protein utilization (NPU) fell markedly in rapidly growing animals aged 45 and 85 days (33 and 30% more than with casein), indicating that without essential amino acid compensation, gluten is inadequate for animals of this age, whose organism requires fully ensured proteosynthesis for growth and development. In adolescence and adulthood (145 and 270 days), the utilization of proteins is not dependent on their quality (the decrease in NPU 13 and 12%--is nonsignificant). That means that a smaller amount of essential amino acids, including the limiting amino acid in uncompensated protein, is sufficient for the maintenance and renewal of organs and tissues, i.e. for proteosynthesis. The activation of gluconeogenesis (phosphoenolpyruvate carboxykinase activity in the liver) after the intake of plant protein confirms the effect of proteins on catabolic processes. PMID- 1286091 TI - Comparison of two approaches to measurement of electrical impedance of glass microelectrodes designed for evaluation of temperature changes in biological tissues. AB - We proposed a temperature sensitive microelectrode for rapid measurements of temperature at the cellular level. In principle, the electrical impedance of the tip of the microelectrode changes with temperature. We designed an impulse measurement system (STEP) sensitive to the above changes of impedance. The system is based on a presettable negative input impedance of the current to a voltage converter. We compared the efficiency of the new STEP with the currently used RAMP system. We found following advantages of the STEP system: i) the danger of high voltage oscillations which could mechanically destroy the microelectrode tip is eliminated; ii) this system provides the opportunity to set the maximum sensitivity of the system according to the measured temperature interval. Moreover, the STEP method makes it possible to measure the resistance by using a sinusoidal stimulation signal which has to be preliminarily compensated by a rectangular signal. The shortest sampling period of the new system represents 0.1 ms with a resolution higher than 0.1 K and sensitivity better than 30 mV/K. PMID- 1286092 TI - Effect of short-term ethanol intake on antibody-dependent cell-mediated cytotoxicity (ADCC) in rats. AB - The present study was designed to evaluate the effect of short ethanol intake on ADCC activity in blood and spleen mononuclear cells. Wistar rats were fed a standard diet and drank 0.1 M ethanol solution for three days. Glucose and water controls were used in this experiment. Increased ADCC activity was found in ethanol consuming rats in the blood and spleen as compared to both controls. Our findings support the assumption that ADCC may play an important role in liver disease of alcoholics. PMID- 1286093 TI - Effect of tubocurarine on the central generator of embryonic spontaneous motility. AB - The continuous administration of d-tubocurarine (6.5 +/- 0.4 mg/kg e.w./24 h) to chick embryos from the 4th to the 12th day of incubation had a positive effect on defects produced in the development of spontaneous motility either by decentralization of the spinal cord or by chemical phenobarbital depression, or by a combination of both experimental factors. In normal embryos, d-tubocurarine had no effect on the development of spontaneous motility. PMID- 1286094 TI - High sensitivity of PHHC rat to dietary cholesterol. AB - The Prague Hereditary Hypercholesterolaemic (PHHC) rat is a strain of the Wistar rat very sensitive to dietary cholesterol. The dynamics of changes in serum and liver lipids and lecithin: cholesterol acyltransferase (LCAT) were studied immediately after the switch to a high cholesterol diet. Immediate cumulation of free and esterified cholesterol in the liver after the increase in alimentary cholesterol intake is supposed to be the regulating step leading to a subsequent increase in serum cholesterol concentration. Activity of LCAT was negatively correlated to the concentration of free cholesterol in the liver, very early after the cholesterol diet was introduced, a possibility of a down regulation of enzyme synthesis similarly to the regulation of synthesis of cholesterol in hepatocytes was observed. PMID- 1286095 TI - Biliary amino acid excretion in rats before and after bilateral nephrectomy. AB - In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics. PMID- 1286096 TI - Increase of slow periodic modulation of EEG in a patient with Alzheimer's disease. AB - The recently described slow oscillations of amplitude of theta and alpha waves of the EEG (with a frequency below 0.08 Hz) in healthy subjects are attributed to the autonomic nervous system with control at the brain stem level. In the present pilot study, the slow brain rhythms were analyzed in a patient with Alzheimer's disease and were compared to a healthy subject. Dynamic analysis of the EEG was performed using time-frequency mapping which gives simultaneous time and frequency representation of the brain signal. This method comprises a transform of the filtered EEG signal into its analytic form and application of the Wigner distribution modified by time and frequency smoothing. It has been shown that the envelope of both theta and alpha activities oscillates at 0.04 Hz and 0.07 Hz in the healthy subject and at 0.03 Hz and 0.06 Hz in a patient with Alzheimer's disease. The amplitude of the slow oscillations of theta activity was substantially higher in the patient with Alzheimer's disease as compared with the healthy subject. It is being proposed that the increase of slow brain rhythms in the patient with Alzheimer's disease reflects an abnormal activity of the autonomic nervous system. However, the underlying pathophysiological mechanisms need to be further studied. PMID- 1286097 TI - Single potassium channels of human glioma cells. AB - Single potassium channels in the membrane of human malignant glioma cells U-118MG were studied using the technique of patch clamp in cell-attached and inside-out configurations. Three types of potassium channels were found which differed from each other under conditions close to physiological in their conductance and gating characteristics. The lowest-conductance channel (20 pS near the reversal potential) showed a mild outward rectification up to 45 pS at positive voltages and spontaneous modes of high and low activity. At extreme values of potentials its activity was generally low. The intermediate conductance channel had an S shaped I-V curve, giving a conductance of 63 pS at reversal, and a low and voltage independent opening probability. The high-conductance (215 pS) channel was found to be activated by both membrane potential and Ca2+ ions and blocked by internal sodium at high voltages. The current-voltage curves of all three channel types displayed saturation. PMID- 1286098 TI - Influence of light regimen and time of year on circadian oscillations of insulin and corticosterone in rats. AB - Male SPF bred Wistar rats were adapted to natural light (N) and to a 12:12 h (light-dark) artificial light (A) regimen in the course of the year. The rats were analyzed at 3 h intervals during 24 h approximately at the time of the vernal and autumnal equinox and at the winter and summer solistice. Serum insulin circadian oscillations depended on the season, being different in various light regimens. The mesors were the highest during summer, the lowest during winter in both regimens. The external acrophases of insulin in the N differed from those in the A group, contrary to the computative ones. The annual mean of serum insulin concentration was lower in the N than in the A group. The circadian oscillations of corticosterone were influenced primarily by the time of year. The mesors were the highest during summer, lower in winter and spring in N and A group. The computative acrophases were similar in both groups in all seasons except spring. The external acrophase was similar in both regimens during the year. The response of insulin, a major anabolic hormone, to various light regimens during the day and year was different from that of corticosterone, a major hormone of the stress reaction. PMID- 1286099 TI - The effect of various photoperiods on daily oscillations of serum corticosterone and insulin in rats. AB - The effect of various photoperiods on circadian rhythms of chosen parameters was investigated in laboratory rats. SPF male Wistar rats were adapted for six weeks to artificial light-dark cycles (LD 8:16, 12:12, 16:8). The light was switched on at 07.00 h in all regimens. The rats were killed at 3-hour intervals within 24 h, the serum concentration of corticosterone, insulin, glucose, food and water intake was determined. The external and computative acrophases of corticosterone varied in every photoperiod being dependent on the duration of light, the mesor values decreased in LD 16:8 in comparison with other photoperiods. The external acrophase of insulin was located 4 h after light onset in LD 8:16 and 12:12, in LD 16:8 one hour before light onset. The mesor values were approximately equal in all photoperiods. The circadian rhythms of glucose were similar in all regimens. Circadian variation of food and water consumption culminated at the same time in all regimens, the amount of food consumed in light increased with the light duration. Various photoperiods remarkably influenced circadian oscillations of corticosterone and in part food and water intake which could be considered as photoperiodic traits. PMID- 1286100 TI - Effect of prostaglandin E2 on the ductus arteriosus in the newborn rat. An ultrastructural study. AB - A patent ductus arteriosus (DA) was maintained in newborn rats (Wistar strain) by administering prostaglandin E2 (PG E2) in doses of 15 micrograms.kg-1 at 30 min intervals up to 300 min after birth. In the control animals, the DA was functionally closed 300 min after birth. The lumen was blocked by clustered endothelial cells at various stages of degeneration. Elastic membranes of the media had disintegrated into irregular fragments and the smooth muscle cells were contracted. Cytoplasm excrescences formed on their surface as a result of contraction protruded as hernias into adjacent muscle cells and into endothelial cells. The smooth muscle cells degenerated. The administration of PG E2 inhibited contraction of the smooth muscle cells and so also the development of degenerative changes; 300 min after birth the DA was fully patent, the elastic membranes were structurally intact, regularly organized and continuous. The smooth muscle cells had the character of synthesizing cells with richly developed granular endoplasmic reticulum. The intima and its endothelial lining were likewise free from structural changes. The ultrastructural image of the wall of the DA correspondent to the state 10 min after birth, when the DA was fully patent. The administration of PG E2 did not induce any ultrastructural changes indicative of injury to the wall of the DA. PMID- 1286101 TI - Critical quantum content for shortening of endplate currents in the frog skeletal muscle. AB - The decay time of endplate currents was followed during progressive lowering of quantum content of endplate responses by reduced Ca2+. A certain critical value of about 100 quanta was found, when the decay of endplate currents remained constant even though the quantal content was reduced further. PMID- 1286103 TI - Resetting of the mammalian circadian clock through lowering of the amplitude: rat pineal N-acetyltransferase rhythm as a model. AB - During resetting of the mammalian circadian clock, not only phase of the clock is shifted, but amplitude of overt rhythms driven by the clock may be temporarily reduced or even abolished. The present paper is aimed to elucidate the mechanism of amplitude reduction of the overt circadian rhythm in the rat pineal N acetyltransferase (NAT). The rhythm has two phase markers, namely the time of the evening NAT rise and that of the morning decline. When the phase relationship between both markers is compressed drastically, the NAT rise may occur just close to or at the time of the decline and consequently the NAT rhythm with a full amplitude cannot be expressed. Such a compression may occur in two ways: either animals are subjected to a considerable advance in the light onset which phase advances the morning NAT decline and at the same time phase delays the evening NAT rise, or they are subjected to a considerable delay in the light offset, which primarily phase delays more the NAT rise than the decline. While in the former case the phase markers move in opposite directions, in the latter case they move in the same direction, but to a different extent. The data suggest a complex structure of the underlying clock. PMID- 1286102 TI - Non-quantal acetylcholine release after cholinesterase inhibition in vivo. AB - After anticholinesterase treatment in vivo, depolarization of the postsynaptic muscle fibre membrane by about 4 mV develops due to non-quantally released acetylcholine from the motor nerve terminal. This conclusion was supported by experiments with the curarization of diaphragm slices from anticholinesterase treated mice during intracellular microelectrode recordings. PMID- 1286104 TI - Differential sensitivity of the brain ATP-dependent and GTP-dependent succinyl CoA synthetase to vanadium ions. Developmental aspects. AB - We have recently found that both vanadate and vanadyl inhibit ATP-dependent succinyl-CoA synthetase (A-SCS) solubilized from the rat brain mitochondria. Aim of the present study was to estimate a proportion of A-SCS to G-SCS in adult and 5-day-old rat brain and their susceptibility to vanadium ions. The G-SCS to A-SCS ratio of 5-day-old brains was by 196% higher than that in adults. This is in accordance with previous observation that G-SCS is high in tissues metabolizing ketone bodies. Both G-SCS and A-SCS differ in their susceptibility towards vanadium ions. A-SCS of adult brain was more sensitive to vanadate (IC 50 1.6.10( 5) mol.l-1) than was G-SCS (IC 50 6.2.10(-5) mol.l-1). On the contrary G-SCS was more sensitive to vanadyl (IC 50 3.5.10(-4) mol.l-1) than was A-SCS (IC 50 9.0.10(-4) mol.l-1). Also autophosphorylation of G-SCS a-subunit was more resistant to vanadate than A-SCS. In contrast to the adult SCS forms, almost equal susceptibility of A-SCS and G-SCS to vanadyl and vanadate was observed in infant brains. The results suggest some structural (functional) differences between two SCS forms in adults and also between infant and adult G-SCS. PMID- 1286105 TI - Morphological changes of the presynaptic and postsynaptic element in excitatory synapses during kindling. AB - In a previous study of a kindling model using stimulation of the entorhinal cortex we found a redistribution of synaptic vesicles into the close vicinity of the active zone of synapses of Type I (Gray 1959) in the hippocampal gyrus dentatus. In this paper, ultrastructural studies of the same model are being continued using planimetry of the synaptic apparatus. A significant increase of the postsynaptic apparatus, area enlargement by 53%, increase of the perimeter by 28% and shape irregularity are being reported. No changes in shape or in size have been demonstrated in presynaptic structures or in the morphology of presynaptic mitochondria. These findings are discussed in relation to increased functional readiness of the synapses as signs of active reconstruction of the synaptic apparatus. PMID- 1286106 TI - Evaluation of endothelium loss by in vitro vessel perfusion using millipore filters. AB - Endothelial loss of isolated rabbit femoral artery and renal artery was evaluated during in vitro vessel perfusion. Desquamated endothelial cells were captured on millipore filters from the perfusion solution outflow of the vessel in 3 intervals lasting 5 minutes each. In the first 5 minutes of perfusion the endothelial loss was 1,289.2 +/- 166.5 cells: in the interval after a 30 minute perfusion 4,967.9 +/- 1,428.3 cells were caught on the filters, 3.9 times more than in the first interval. During and after the 2 minutes air bubble perfusion the endothelial catch was 5.5 times greater as compared to the second interval with the average of 27,473 +/- 6,209.6 cells. The present method of quantification of the endothelial cell loss in the in vitro vessel perfusion experiment makes it possible to obtain informations about the actual state of the endothelial lining and to contribute to more precise evaluation of the modulatory effect of the endothelium on vessel reactivity to pharmacological agents. PMID- 1286107 TI - Hypoxia and fatty acids in immature nervous tissue in the rat. AB - In experiments on 2-day-old rats (Wistar strain, our own breed), we studied the effect of altitude hypoxia (9000 m, 60 min) on the proportion of individual fatty acids in the brain (the cortex+the diencephalon+the cranial third of the mesencephalon). We found that hypoxia significantly altered the proportion of the various fatty acids, with a significant increase in the proportion of group n-3 polyenoic fatty acids at the expense of saturated and monoenoic acids. The results fully confirm the conception that one of the most important mechanisms responsible for the high resistance of new born mammals to oxygen deficiency is the ability of immature nervous tissue to activate, in particular, elongation (the elongation of fatty acids) and/or lipogenetic processes. PMID- 1286108 TI - Motion-reversal visual evoked responses. AB - Motion-reversal visual evoked responses (VERs) have remarkable waveform variability. In our opinion this is caused by the alternative predominance of either motion or pattern-onset/offset related components. The motion dependent component of motion-reversal VER closely resembles motion-onset VER (main negative peak with the latency of about 170 ms), the first positive peak (with the latency of about 100 ms) corresponds to the pattern-onset component and the second non-constant positive peak (with the latency of about 130 ms) seems to be identical with the pattern-offset positivity. The differences in expression of these components are dependent on some stimulus characteristics (mainly on the contrast of a structure, velocity of motion, retinal localization of the stimulus) and on substantial differences in the sensitivity of subjects to motion stimulation. PMID- 1286109 TI - Hypoventilation after acute phrenicotomy of the urethane anaesthetized rats. AB - The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i.p.); other 8 rats were sham operated (SX). Ventilation, PaCO2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in PaCO2 compared with the control values and with that in the SX rats. The increase in PaCO2 was accompanied by an increase in the peak amplitude of the iEMG to 155 +/- 18% of control values after PX and to 228 +/- 33% 4 hours later. Despite the augmented EMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm. PMID- 1286110 TI - Effect of sialoadenectomy on stomach lesions induced by indomethacin and ethanol in relation to gastric vascular permeability, the gastrin level and HCl secretion in rats. AB - Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF. PMID- 1286112 TI - Different effects of oestradiol benzoate and norethisterone on the blood flow and mineral content in rat bones. AB - In three experiments (2 on females, 1 on males), we determined the blood flow in the tibia and the distal part of the femur, together with cardiac output (by means of 85Sr-microspheres), tibial bone density and tibial ash weight related to bone volume. We found that 1) the bone blood flow always fell significantly after oestradiol benzoate, 2) no change occurred after norethisterone in doses corresponding to those of oestradiol benzoate, but the blood flow showed a tendency to fall after doses one order higher (it decreased significantly in one case only), 3) the density of the tibia and tibial ash weight related to bone volume rose nonsignificantly after oestradiol benzoate, but fell (mostly statistically significantly) after norethisterone. The lowering of the bone mineral indexes in rat bones after norethisterone is a surprising and potentially significant finding requiring further verification. PMID- 1286111 TI - The effect of administration of estradiol and testosterone on body growth of young male rats. AB - The influence of estradiol and testosterone on body growth of young male Wistar rats was investigated. In the first experiment, estradiol was given to intact ad libitum fed male rats at 32, 37 and 42 days of age. Moreover, two untreated groups of animals were used: one was fed restrictedly according to the food intake of animals receiving estradiol and another was fed ad libitum. The animals were sacrificed at 47 days of age. Both untreated groups of animals achieved significantly higher body weight and length of tibia than estradiol treated animals. Also the growth of the tail of untreated animals was more intensive than that of estradiol treated animals. In the second experiment, estradiol was given to intact ad libitum fed male rats at 30, 35 and 45 days of age. Moreover, testosterone was given to a half of these animals at 45, 50 and 55 days of age. The animals were sacrificed at 60 days of age. Administration of testosterone significantly increased the growth of the tail and tibia in comparison to the animals which did not receive testosterone after estradiol administration. The results of the present study show that the inhibitory effect of estradiol on body growth of young male rats is not only the result of decreased food intake and that testosterone can improve the skeletal growth of male rats altered by previously given estradiol. PMID- 1286114 TI - Protective effect of ascorbic acid in high altitude hypoxia in the rat. AB - Control (physiological saline treated) and ascorbic acid (AA) treated (1 mg.g-1 b.w. one hour before exposure) 18-day-old rats were exposed for 1 hour to high altitude in a hypobaric chamber and the mean lethal altitudes were calculated. AA displayed a protective effect, so that in two identical experiments the mean lethal altitude was 10,900 and 10,150 m in controls, while it was 11,500 and 11,450 m in AA treated animals. PMID- 1286113 TI - Acute toxicities of 2-dialkylaminoalkyl-(dialkylamido)-fluoro-phosphates. AB - Toxicities expressed as LD50 values of 2-dialkylaminoalkyl-(dialkylamido) fluorophosphates for rats and mice (i.m. administration) were determined. Rats were more sensitive to these compounds than mice: LD50 values varied from 17 (rats) to 1222 (mice) micrograms/kg. LD50 values at different routes of administration (i.v., i.m., s.c., p.o. and p.c.) for one derivative of this group, 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate, were determined. Depending on the route of administration, LD50 values varied from 11 (i.v.) to 190 (p.o.) micrograms/kg for rats and from 27.6 (i.v.) to 222 (p.o.) micrograms/kg for mice, respectively. Percutaneous toxicity in rats only (LD50 = 1366 micrograms/kg) was determined. PMID- 1286115 TI - Syphilis: new diagnostic directions. PMID- 1286117 TI - Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population. AB - A retrospective study was performed in a department of genitourinary medicine to determine the prevalence and clinical features of urethral and cervical infection with Neisseria meningitidis among patients being screened for sexually transmitted diseases. During the 28 month period of the study 11 isolates (from 10 patients) of N. meningitidis were identified from 5571 urethral cultures from homosexual men (0.2%). This compares with an isolation rate of 4.7% for N. gonorrhoeae; 1.2% samples screened for chlamydial antigen were positive. There were no isolates from 8992 urethral cultures from heterosexual men or 15,976 cervical cultures. Eight of the cases identified had features of urethritis at diagnosis; 6 were diagnosed initially as non-specific urethritis (NSU) and 2 as gonorrhoea on the basis of microscopy of a urethral smear. Eight of the 10 patients were treated with amoxycillin and/or a tetracycline, and all but one had a clinical and microbiological cure. In the study population the prevalence of N. meningitidis infection was low and restricted to homosexual men; however, it may be associated with symptoms. PMID- 1286116 TI - The role of maternal syphilis, gonorrhoea and HIV-1 infections in spontaneous abortion. AB - The role of the human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) as risk factor for spontaneous abortion was investigated in a case-control study in Nairobi, Kenya. Cases (n = 195) were women admitted with clinical signs and symptoms of spontaneous abortion, before 20 weeks of gestation. Patients with induced or clinically septic abortion were excluded. Controls were unselected pregnant women in their second or third trimester (n = 195). Spontaneous abortion was independently associated with maternal HIV-1 antibody (14.4% versus 6.2%; adjusted odds ratio, 2.3; 95% confidence interval, 1.1-4.8), with maternal syphilis seroreactivity (6.8% vs 2.1%, adjusted odds ratio, 4.3; 95% confidence interval 1.2-15.6), and with vaginal colonization with group B streptococci (15.6% vs 5.2%; adjusted odds ratio, 3.2; 95% confidence interval, 1.5-6.7). No significant association was found between maternal infections with gonococci and genital mycoplasmas, and spontaneous abortion. PMID- 1286118 TI - The impact of HIV disease on an Irish prison population. AB - Between January 1987 and January 1991, 168 known HIV-infected prisoners have been incarcerated in Dublin's Mountjoy prison. This figure constitutes 16.6% of the total HIV-infected population in the Republic of Ireland over the same period. One hundred and forty-one (84%) of these prisoners have attended the Department of Genitourinary Medicine, St James's Hospital, Dublin. This group displayed considerable morbidity from HIV-related disease. Respiratory tract infection was the most frequent complication seen. Much additional morbidity was directly attributable to intravenous drug use. A survey of a representative group of inmates revealed that 64.7% were diagnosed HIV-positive in prison. The mean length of time spent incarcerated since the diagnosis of HIV infection was 38.9 months. Twenty-nine of 34 individuals who answered a questionnaire were imprisoned for drug-related crimes and 32 of 34 prisoners admitted to parenteral drug use within the prison. As the HIV epidemic unfolds in Dublin, increasing numbers of prisoners with symptomatic HIV disease will spend time incarcerated in Mountjoy prison. This will pose a considerable burden on prison and hospital medical services alike. PMID- 1286119 TI - Gonorrhoea: signs, symptoms and serogroups. AB - Over 19 weeks, 104 male patients attending a genitourinary medicine clinic with gonococcal urethritis were asked to complete a questionnaire detailing symptoms. Sixty-seven questionnaires were duly completed. The examining nurse documented signs. Ninety-one isolates of Neisseria gonorrhoeae were serogrouped and auxotyped, 55 of these were from patients who had completed a questionnaire. Patients presented earlier if they had a past history of gonorrhoea (p = 0.02). The serogroup of N. gonorrhoeae did not influence the amount of discharge, the presence of meatal inflammation, dysuria or penile tip irritation or the delay in presentation after appearance of discharge. Auxotype AHU was not associated with asymptomatic gonorrhoea. PMID- 1286120 TI - Prevalence of urogenital Chlamydia trachomatis infection in El Salvador. II. Gynaecology outpatients. AB - The prevalence of urogenital infection caused by Chlamydia trachomatis was examined in 100 non-pregnant women with cervicitis, and 100 healthy women, in San Salvador City, El Salvador. Pharmacia Chlamydia EIA test was used for the detection of chlamydial antigen in urethral and cervical specimens from all the women. Direct immunofluorescence was used for confirmative tests on the EIA positive and the negative gray zone samples. C. trachomatis antigen was detected in 28% of the women with cervicitis compared with 5% in the group of healthy women (P < 0.001). The cervicitis group were also screened for Neisseria gonorrhoeae which was isolated from 12% of them. One strain out of 12 was beta lactamase producing (PPNG). Five per cent of the women with cervicitis had simultaneous C. trachomatis and N. gonorrhoeae infections. PMID- 1286121 TI - Sexual behaviour amongst travellers: a study of genitourinary medicine clinic attenders. AB - Two hundred and fifty attendees at two London genitourinary medicine clinics were asked to complete an anonymous self-administered questionnaire, enquiring about sexual behaviour whilst abroad. Two hundred and forty-three questionnaires were evaluable. In the study group there were 116 women, and 127 men (62 heterosexuals and 65 homosexuals). Ninety women, 53 heterosexual men and 53 homosexual men had travelled abroad over the preceding 6 months. Of these 18 (20%) of women, 26 (51%) of heterosexual men and 19 (36%) of homosexual men had sex with a local foreign contact on holiday. Although both heterosexual and homosexual men were statistically more likely to have sex abroad with a local inhabitant, women were more likely to have unprotected sexual intercourse with a local partner. This has important implications for the spread of sexually transmitted disease including hepatitis B and HIV. PMID- 1286122 TI - Treatment of anogenital warts in genitourinary clinics in England and Wales. AB - A questionnaire on the treatment of anogenital warts was sent to 150 consultants in genitourinary medicine, 78 (52%) were returned completed. A wide range of treatments were used; podophyllin was the commonest first line treatment of multiple penile (60.3%), perianal (57.7%) and vulval (61.5%) warts. Cryotherapy was a popular choice for intrameatal warts (65.3%), small numbers of vulval warts (33.3%) and as second line therapy for penile (35.9%) and perianal (33.3%) warts. Vaginal warts were treated with podophyllin (39.7%) or cryotherapy (29.5%). Various combinations of podophyllin, trichloroacetic acid and cryotherapy were used (2.6%-24.3%) although there is no evidence this offers benefit over single therapy. Podophyllin is frequently used despite side effects, a poor clearance rate and in vaginal warts, difficult access. Initial therapy with more time consuming procedures such as cryotherapy or electrocautery may be of benefit to selected patients. PMID- 1286123 TI - Atypical presentations of herpes simplex virus infection. PMID- 1286124 TI - An inguinal bubo caused by Mycobacterium chelonae abscessus. PMID- 1286126 TI - Aids literature index. PMID- 1286125 TI - Survey of attitudes of a sexually transmissible diseases clinic staff to the proposed creation at that clinic of a comprehensive sexual health centre. PMID- 1286127 TI - Characterization of sulphoalkyl ether derivatives of beta-cyclodextrin by capillary electrophoresis with indirect UV detection. AB - A capillary electrophoresis method which characterizes the degrees of substitution of heterogeneous sulphoalkyl ether beta-cyclodextrin derivatives is described. The separation is based on the different electrophoretic mobilities observed from changes in the overall charge of the molecule as a result of substitution. Individual peaks of the electropherogram then provide a measure of each degree of substitution of the present beta-cyclodextrin. Detection of these beta-cyclodextrin derivatives is performed by indirect UV detection. PMID- 1286128 TI - Pharmacokinetics of 2-(alpha-thenoylthio)-propionylglycine (TTPG) in healthy volunteers--an oral dose-proportionality investigation. AB - The dose linearity of 2-(alpha-thenoylthio)-propionylglycine (TTPG) pharmacokinetics after a single oral administration at three different TTPG doses (180, 540 and 1080 mg) was evaluated in 12 healthy volunteers according to an open, randomized, cross-over study with a 1-week wash-out period between each administration. The duration of the study, for each subject, was 4 weeks. Plasma concentration and urinary excretion of TTPG and its two systemic metabolites, namely propionylglycine (tiopronin) and thiophenecarboxylic acid (TCA) were assayed by a previously well validated HPLC method. Due to differences in the physical and chemical properties of these compounds, two assays were needed, one to measure TTPG and TCA as such, and one to measure derivatized tiopronin. Both used UV detection. TTPG, tiopronin and TCA were quickly detected in plasma, suggesting that the drug administered is rapidly absorbed and biotransformed, in part, in the systemic circulation into the two metabolites noted above. Time-to peak for all three analytes showed a trend to increase with increasing doses of TTPG, being: 0.42, 0.40 and 0.67 h (P < 0.01) with TTPG; 0.53, 0.47 and 0.73 h (P < 0.05) with TCA; and 1.33, 2.13 and 2.58 h (P < 0.01) with tiopronin. Cmax showed the opposite behaviour with values (ng ml-1) normalized to the dose of 540 mg: 1235, 905 and 513 (P < 0.001) with TTPG; 888, 547 and 383 (P < 0.001) with TCA; and 7290, 6950 and 5170 (P < 0.01) with tiopronin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286129 TI - Gold concentrations in blood fractions of patients with rheumatoid arthritis treated with Myocrisin. AB - Gold levels in the plasma and blood cells of patients treated with the gold drug Myocrisin (sodium aurothiomalate) were determined by atomic absorption spectrometry. There is a correlation between whole blood gold and plasma gold concentrations which is different for smokers and non-smokers. Most cellular gold is associated with the membrane and is present in concentrations approximately equivalent to the number of reactive sulphydryl groups on the exofacial surface of the cell. Since gold would be expected to react with SH groups and since these groups are vital for cellular function, a possible role for gold in modifying cellular metabolism is indicated. PMID- 1286130 TI - Photodegradation kinetics under UV light of aztreonam solutions. AB - A photodegradation study of aztreonam solutions exposed to UV irradiation showed that the major product of degradation was the anti-isomer together with some unidentified products. This result was similar to that obtained with cefotaxime and it is postulated that this would be generally true of compounds containing an alkoxyimino group. PMID- 1286131 TI - Supercritical fluid chromatography of selected oestrogens. AB - The separation of selected oestrogens (oestrone, equilin, alpha-oestradiol, beta oestradiol and d-equilenin) using capillary supercritical fluid chromatography (SFC) was studied. Three different stationary phases (SB-methyl-100, SB-biphenyl 30 and SB-cyanopropyl-50) were studied for the separation of the compounds. A baseline separation of the oestrogens was achieved on a SB-cyanopropyl-50 column using a carbon dioxide density gradient at an oven temperature of 73 degrees C. Typical analysis time on a 7 m column was 21 min. Retention times of each oestrogen decreased with an increase in either mobile phase density or oven temperature. Accuracy and precision of the SFC method were in the 1-5.5% range. The SFC method was applied to three different dosage forms containing oestrogens. PMID- 1286132 TI - Degradation of dacarbazine in aqueous solution. AB - The effects of initial concentration (0.05-5.0 mg ml-1, 2.5 x 10(-4)-0.025 M) (pH 1-13), buffer concentration (0.01-0.075 M), light, antioxidants and co-solvents on the degradation of dacarbazine in aqueous solution were investigated at 37 degrees C. Liquid chromatography was used to monitor the degradation of dacarbazine as well as the appearance of degradation products. The kinetics of hydrolysis of dacarbazine in the dark were pseudo first-order and independent of the initial concentration of the drug. The degradation of dacarbazine was accelerated by light and at low concentration proceeded by pseudo zero-order kinetics. The pH-rate profiles showed that both the photolytic and the hydrolytic reactions were dependent on the ionization state of the molecule. The main degradation product of both hydrolysis and photolysis was detected by liquid chromatography and confirmed by mass spectrometry to be 2-azahypoxanthine. PMID- 1286133 TI - The identification of related substances in triamcinolone acetonide by means of high-performance liquid chromatography with diode array detector and mass spectrometry. AB - A study of an HPLC method for the analysis of related substances in triamcinolone acetonide is described. Several systems of solvents and samples of different lots and preparative origins were examined and a rapid-scanning diode array UV detector (DAD) was particularly useful. With the proposed technique it was possible to identify 9 alpha-bromo desonide as a principal impurity, which was present in all examined samples of triamcinolone acetonide. This identification was rendered possible by the investigation of the second derivative of the UV spectra and by means of study of the mass spectrum. Furthermore, it was possible, primarily on the basis of the spectrophotometric data, to formulate reliable hypotheses on the possible identification of 9 beta, 11 beta-epoxide of the desonide which was present at very low levels and to exclude the presence of 11 deoxy-9(11)-unsaturated desonide. The presence of the above-mentioned related substances was explained considering the scheme of synthesis described in the literature. The spectrophotometric characteristics of the studied compounds and the limits of applicability of the present procedure are discussed. PMID- 1286134 TI - Simultaneous determination of simvastatin and its hydroxy acid form in human plasma by high-performance liquid chromatography with UV detection. AB - Simvastatin (SV), an analogue of lovastatin, is the lactone form of 1',2',6',7',8',8a'-hexahydro-3,5-dihydroxy-2',6'-dimethyl-8'(2'',2''-di met hyl 1''-oxobutoxy)-1'-naphthalene-heptanoic acid (SVA) which lowers plasma cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase. A fast, simple and accurate method for determining SV and SVA concentrations in human plasma has been developed and validated for use in the analysis of plasma samples from patients and healthy volunteers. This method involves an extraction procedure using a mixture of acetonitrile-water and reversed-phase high performance liquid chromatography with UV detection. The procedure was linear from 20 to 1000 ng ml-1 for SV and from 25 to 1000 ng ml-1 for SVA, respectively. The method was accurate with relative errors of 5.0, 2.1 and 3.2% for human plasma controls containing 50, 250 and 500 ng ml-1 of SV, respectively. The corresponding precision was 2.3, 1.8 and 1.0% (RSD%). Similarly, relative standard deviations less than 2.3% and relative errors of less than 5.2% were obtained from human plasma controls containing SVA at identical concentrations. The method is suitable for pharmacology and pharmacokinetic studies of simvastatin. PMID- 1286135 TI - Discrimination of bovine and porcine insulin by higher-order derivative UV spectroscopy. PMID- 1286136 TI - Triglyceride, high density lipoprotein, and coronary heart disease. AB - The National Institutes of Health Consensus Development Conference on Triglyceride, High Density Lipoprotein, and Coronary Heart Disease brought together experts in lipid metabolism, epidemiologists, and clinicians as well as other health care professionals and the public to address the following questions: (1) is the relationship of high triglyceride and/or low HDL cholesterol with coronary heart disease causal? (2) Will reduction of high triglyceride and/or elevation of HDL cholesterol help prevent coronary heart disease? (3) Under what circumstances should triglycerides and HDL cholesterol be measured? (4) Under what circumstances should active intervention to lower triglyceride and/or raise HDL cholesterol be considered in high risk individuals and the general population? (5) What can be accomplished by dietary, other hygienic, and drug treatments? (6) What are the significant questions for future research? Following two days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel concluded that (1) existing data provide considerable support for a causal relationship between low HDL and CHD; however, with respect to TG data are mixed and the evidence on a causal relationship is incomplete; (2) initial TG and/or HDL levels modify benefit achieved by lowering low density lipoprotein cholesterol (LDL-C); however, evidence from clinical trials is insufficient to draw conclusions about specific benefits of TG and/or HDL altering therapy; (3) HDL-C measurement should be added to total cholesterol measurement when evaluating CHD risk in healthy individuals provided accuracy of measurement, appropriate counseling, and followup can be assured; (4) there is general agreement with the Adult Treatment Panel (ATP) guidelines that LDL-C is essential in cardiovascular risk assessment, as well as that persons with elevations of LDL-C greater than 150 mg/dl refractory to nondrug therapies may require drug treatment; (5) there is a strong consensus that hygienic approaches (diet, exercise, smoking cessation, weight loss) should be employed to lower TG and/or raise HDL; there is no consensus for the use of drug treatment in patients with borderline hypertriglyceridemia and low HDL-C levels in the presence of a desirable LDL-C level. PMID- 1286137 TI - The diminution of liver glutathione content and changes in activities of antioxidant enzymes in long-term acetaldehyde poisoning. AB - The effect of acetaldehyde administration for 4 weeks on antioxidant protection systems was investigated in liver of rats. Liver SOD activity was decreased from control value 542.4 U/g of tissue to 411.2 U/g of tissue in experimental group (24% decrease). GSH-Px activity was practically unchanged and liver CAT activity was significantly decreased (35%). Sulfhydryl compounds in liver non-proteins following ACH treatment were decreased from 4.22 mumol/g of tissue in control group to 2.86 mumol/g of tissue (23%). Furthermore acetaldehyde treatment caused significant increase in MDA level in liver (78% increase). PMID- 1286138 TI - Fibrin stabilizing factor activity of the skin carcinoma. AB - Activity of fibrin stabilizing factor and contents of sulphydryl group in the homogenate of malignant skin carcinomas (melanoma, spinocellular carcinoma, basal cell carcinoma, fibromyoma, liposarcoma) is higher than in the homogenate of benign neoplasm (lipoma, papilloma) and in the homogenate of the normal skin. Fibrin stabilizing factor activity and contents of sulphydryl group in the blood serum of subjects with malignant skin carcinomas is slightly lower than in the blood serum of subjects benign neoplasm and in healthy subjects. PMID- 1286139 TI - The effect of quercetin and lithium ions on platelet aggregation. AB - Quercetin inhibited aggregation of porcine blood platelets induced by collagen (IC50 = 0.2 mM), ADP (IC50 = 0.5 mM), thrombin (IC50 = 0.02 mM) and ionophore A23187 (IC50 = 1.5 mM). Preincubation of platelets with 10 mM LiCl abolished the inhibitory effect of quercetin on the aggregation of these cells induced by thrombin. Lithium ions per se caused potentiation of the aggregation of platelets induced by thrombin. Neither potentiation of aggregation by Li+, nor the abolishing of the inhibitory effect of quercetin by Li+ was observed when platelets were activated by ionophore A23187. Since lithium ions inhibit activity of enzymes degradating inositol phosphate, the obtained results can be interpreted to mean that quercetin affect platelet aggregation by the inhibition of inositol phosphates production. PMID- 1286140 TI - AMP deaminase from porcine blood platelets, regulation by adenine nucleotides, phosphate and by Na+ and K+ ions. AB - Porcine blood platelets contain a relatively high amount of AMP deaminase (14.4 U per 10 11 cells). The enzyme showed sigmoidal behaviour as a function of AMP concentration with a S0.5 value (substrate concentration required for half maximum velocity) of 3.6 and 4.0 mM in the presence of Na+ and K+ respectively. MgATP and MgADP at micromolar concentration activated the enzyme. Activation by saturating MgATP and MgADP in the presence of Na+ or K+ converted the rate versus substrate plots to hyperbolic with a dramatic decrease of S0.5. Phosphate at milimolar concentrations inhibited the enzyme and this inhibitory effect was totally reversed as the concentrations of MgATP and MgADP rised to physiologically high levels. Na+ and K+ activated the enzyme in the absence of MgATP and MgADP. Both cations largely enhanced the Vmax with Na+ being more potent. A comparison of the kinetic behaviour of the enzyme in vitro with the metabolite concentrations in vivo suggest that a substantial regulation can occur through changes in AMP and Na+ concentrations. PMID- 1286141 TI - Direct muscular neurotization as a method of treatment of irreparable nerve injuries. AB - Authors have presented of 12 patients with irreparable nerve injuries treated by direct motor nerve implantation into muscle belly (direct muscular neurotization). Results were evaluated in Sunderland scale. Motor function of the neurotized muscles following 12 months from operation was in range of between M3 and M4. PMID- 1286142 TI - The serum immunoglobulins level in maxillofacial bacterial infections. AB - The IgG, IgA and IgM levels in the serum of 23 patients with maxillofacial bacterial infections were determined. The high IgG level noted on admission further increased in the serum of 14 patients with acute inflammation and decreased in the serum of 10 patients with a chronic course. The level of IgM in the serum of patients with acute inflammation was higher than in the patients with chronic inflammation and decreased in both groups on the 7th day of treatment. The IgA level was high on admission in both groups and fell on the 7th day of treatment. Our results suggest that analysis of the serum level of IgG, IgA and IgM may be of diagnostic and prognostic value in the treatment of maxillofacial bacterial inflammation. PMID- 1286143 TI - The results of laminectomy and laminoplasty in cervical myeloradiculopathy. AB - The authors present the results of laminectomy and laminoplasty in 20 patients with cervical myeloradiculopathy according to the JOA score. Improvement was noted in 74% of the patients after laminoplasty and in 70% of the patients after laminectomy. On the whole decompression is a good method of treatment in this kind of disease. PMID- 1286144 TI - [Mechanical characteristics of biological soft tissue]. AB - In a detailed study mechanical properties of tendons, muscles, nerves, blood vessels and skin of just slaughtered pigs have been investigated in nearly stationary stress tests. Tensile tests have produced tensile strength, ultimate stress and their appropriate strains, Young's modulus and the work up to fatigue of samples. In hysteresis tests the deformation work has been determined as a function of numbers of stress cycles. The hysteresis decrease with the number of stress cycles and approaches asymptotically to cero. By preconditioning of tendons, nerves and blood-vessels to steady state significant differences of strain at tensile strength and of Young's modulus have been established. Moreover for nerves the tests have revealed significant deviations of tensile strength. Bruise tests have been carried out with muscle tissue. For the described setup the limit force can be specified, at which pathological changes appear. Subsequently conducted histological investigations have demonstrated this. In dynamical bruise tests there appeared no pathological changes in muscle tissue in spite of higher transmitted energy. PMID- 1286145 TI - [Tensile strength studies of self-cutting titanium osteosynthesis screws]. AB - The tapping screws of the Medicon Osteosynthese System applied in the jaw and facial area were checked for their mechanical sturdiness. Screwing tests with bones and aluminium were carried out. The minimum fracture moment, the moment transferrable by the screw slot and the required moment for a tight seat of the Osteosynthese plate on the bone surface were calculated. The screws and plates are of titanium alloy TiA16V4 (US standard) for implantats. In a sample taken at random of test screws the fracture moments were measured and examined. All the screws support considerable loads and the fracture moments are almost 20% higher that the minimum fracture moment for TiA16V4 screws specified in DIN 267, part 18. PMID- 1286147 TI - EEG classification by learning vector quantization. AB - EEG classification using Learning Vector Quantization (LVQ) is introduced on the basis of a Brain-Computer Interface (BCI) built in Graz, where a subject controlled a cursor in one dimension on a monitor using potentials recorded from the intact scalp. The method of classification with LVQ is described in detail along with first results on a subject who participated in four on-line cursor control sessions. Using this data, extensive off-line experiments were performed to show the influence of the various parameters of the classifier and the extracted features of the EEG on the classification results. PMID- 1286146 TI - [Exposure of surgical/orthopedic operating room personnel to monomer vapors during the use of bone cements--review of the literature and report of experiences]. AB - PMMA bone cements are used for the fixation of artificial joint replacements. During their application in the operating theater, a small amount of the monomer evaporates. Operating room staff and surgeons are often not adequately informed about the negative properties and the effects on health of these vapours. Basic information about monomers and their toxicity, and safety regulations have been compiled. On the basis of present knowledge, the authors do not regard the repeated use of bone cement throughout the course of a day to represent a hazard to health. PMID- 1286148 TI - Distance distribution in a dye-linked oligonucleotide determined by time-resolved fluorescence energy transfer. AB - Fluorescence energy transfer is potentially a useful technique for obtaining structural and dynamic information on duplex and branched DNA molecules suitably labeled with donor and acceptor dyes. We have assessed the accuracy and limitations of FET measurements in nucleic acids with respect to the localization of the dyes and the flexibility of the dye-DNA linkages. A nine base-pair duplex oligonucleotide was synthesized with donor and acceptor dyes linked at the opposing 5' termini by alkyl chains. A careful analysis of the fluorescence decay of the donor revealed that the donor-acceptor distance in this molecule was not well defined, but was described by a rather broad distribution. The mean donor acceptor distance and the distribution of distances have been recovered from the donor decay. Orientational effects on energy transfer have been included in the analysis. The implications of these findings for FET measurements in nucleic acids are considered. PMID- 1286149 TI - A computational and experimental study of the bending induced at a double-triple helix junction. AB - We have studied the conformation of a 17 base-pair homopyrimidine.homopurine triple helix formed on a fragment of duplex DNA derived from Simian Virus SV40. Gel retardation assays indicate that an 80 base-pair fragment has an altered conformation when the triple helix is formed, which is most likely to result from an induced bend in the DNA. Investigation of the detailed conformation of the double helix-triple helix junctions has been performed by means of molecular modelling. Bending on the 5' and 3' sides of the third strand oligonucleotide are not located at equivalent positions with respect to the junctions, which is explained in terms of base stacking. The junction effects on DNA structure, induced by the requirement for cytosine protonation in the Hoogsteen-bonded strand to form CGC+ base triplets, are also discussed. PMID- 1286150 TI - Unique and independent parameters (UIP) formulation for thermodynamic models of complex protein-ligand systems. AB - A method for reformulating the thermodynamic (delta G) description of complex equilibria is presented. The purpose of this reformulation is to take a system of N complexes which is completely defined by N delta Gs, and recast it in terms of a new set of N delta Gs. This reformulation is an extension of the concept of interaction energy (J. Wyman, Adv. Protein Chem. 19 (1964) 223-286). The new delta Gs obtained by this reformulation reflect the intrinsic properties of the binding sites and the hierarchical nature of potential interactions between them. A simple set of rules are developed which allow for the description of complex protein-ligand binding schemes and these rules are used to derive schemes for hemoglobin O2 binding. This reformulation represents the foundation for the theoretical description of the coupling of energy in protein-ligand systems as illustrated by the theoretical analysis of allosterism in a dimeric protein presented in the following paper. This reformulation also provides the foundation for the analysis of data pertaining to complex equilibria. PMID- 1286151 TI - Thermodynamic model of cooperativity in a dimeric protein: unique and independent parameters formulation. AB - A model of the cooperative interaction of ligand binding to a dimeric protein is presented based upon the unique and independent parameters (UIP) thermodynamic formulation (Gutheil and McKenna, Biophys. Chem. 45 (1992) 171-179). The analysis is developed from an initial model which includes coupled conformational and ligand binding equilibria. This completely general model is then restricted to focus on conformationally mediated cooperative interactions between the ligands and the expressions for the apparent ligand binding constant and the apparent ligand-ligand interaction constant are derived. The conditions under which there is no cooperative interaction between the ligands are found as roots to a polynomial equation. Consideration of the distribution of species among the various conformational states in this general model leads to a set of inequalities which can be represented as a two dimensional plot of boundaries. By superimposing a contour plot of the value of the apparent ligand-ligand interaction constant over the plot of boundaries a complete graphical representation of this system is achieved similar to a phase diagram. It is found that the parameter space homologous to Koshland-Nemethy-Filmer type of model is most consistent with both positive and negative cooperativity in this model. The maximal amount of positive and negative cooperativity are found to be simple functions of Kc, the equilibrium constant associated with the change of a subunit and ligand from the unligated to ligated conformation. It is shown that under certain limiting conditions the apparent allosteric interaction between ligands is equal to the conformational interaction between subunits. The methods presented are generally applicable to the theoretical analysis of thermodynamic interactions in complex systems. PMID- 1286152 TI - Different superstructural features of the complexes between spermine and the light responsive elements of the two pea genes rbcS-3A and rbcS-3.6. Gel electrophoresis and circular dichroism studies (Biophysical Chemistry 44 (1992) 99-112). PMID- 1286153 TI - Introduction: new anticancer drug design and discovery based on advances in molecular oncology. PMID- 1286154 TI - Potential therapeutic targets in multistep oncogenesis. AB - There are three important considerations in the development of novel drug therapies: firstly, whether a suitable target can be accurately defined; secondly, does the target allow discrimination between normal cells and tumour cells; and thirdly, how easily could the tumour cells acquire resistance? This article will concentrate on two of the genetic alterations most commonly associated with multistep tumourigenesis, and discuss their potential as therapeutic targets with respect to the considerations above. PMID- 1286155 TI - Drugs active against growth factor and oncogene phosphatidylinositol signalling pathways. AB - Increased knowledge of growth factor and oncogene intracellular signalling presents us with unique opportunities to develop new classes of antiproliferative drugs. The degeneracy of intracellular signalling may allow normal cells to be relatively unaffected by drugs that inhibit just one signalling pathway. Oncoproteins themselves have proved difficult to target and the drugs lack selectivity. More success has come with drugs targeted against other components of signalling pathways. Two examples of such classes of drugs are given. The ether lipid anticancer drugs inhibit intracellular signalling at multiple points; phosphatidylinositol phospholipase C, protein kinase C, intracellular Ca2+ release and phosphatidylinositol-3'-kinase. D-3-deoxy-3-substituted myo-inositols and phosphatidylinositols are a new class of growth inhibitory compounds that appear to act as antagonists of myo-inositol signalling. PMID- 1286156 TI - Protein kinase C modulation. AB - PKC-modulators represent valuable additions to the arsenal of anti-tumor agents. They act as antiproliferative agents and are useful in overcoming drug-resistance by inhibiting mdr-mediated drug efflux. They increase the cytotoxicity to platinum complexes (and other DNA-damaging agents), probably by interfering with drug-induced detoxification and repair mechanisms. PKC-modulators are potentially active in overcoming ras-induced cis-platinum-resistance by antagonizing p21ras functions. PMID- 1286157 TI - Modulation of adenylate cyclase signalling. AB - Adenylate cyclase via production of cyclic AMP (cAMP) can transduce dual signals, positive and negative, on cell growth and differentiation. Such dual signals are transmitted by RI and RII cAMP-binding receptor proteins respectively, the regulatory subunits of cAMP dependent protein kinases. The growth stimulatory RI and inhibitory RII are in a strict balance to maintain normal cells, and departure from such balance can cause a great variety of human diseases, including cancer. Experimental approaches using site-selective cAMP analogues, antisense oligodeoxynucleotides, and gene transfer have shown that restoration of the normal balance of RI/RII provides a biological means to the suppression of malignancy. PMID- 1286158 TI - Tyrosine kinase inhibitors. AB - Tyrosine kinases are associated with the cytoplasmic domains of growth factor receptors as well as oncoproteins and many have the potential to cause transformation if mutated or hyperexpressed. Tyrosine kinases therefore represent an excellent target for the development of cancer drugs. A large number of inhibitors have now been identified and many show promising cytostatic activity, particularly using in vitro models. Some in vivo activity has been reported. Progress with various structural classes is reviewed. It is not clear whether specific or broad spectrum tyrosine kinase inhibitors should be developed as potential anticancer drugs. It does seem likely, however, that tyrosine inhibitors will enter clinical trial in cancer patients. PMID- 1286159 TI - Pharmacological probes of Ras function. AB - Numerous approaches toward anti-ras drugs are being explored. Efforts range from cell-based assays which screen fermentation products to more structural or mechanism-based in vitro screening and design. For the mechanism-based approaches, extensive research efforts on the function and regulation of the ras oncogene protein have identified potential points of intervention, including protein expression, membrane localization, guanine nucleotide activation, and interaction with effector systems. PMID- 1286160 TI - Antisense oligonucleotides. AB - Growing evidence indicates that antisense oligodeoxynucleotides can specifically inhibit gene expression thereby providing an essential tool for understanding gene function and the potential to affect abnormal cell proliferation. Because oncogene activation is intimately involved in tumour initiation and progression, down-regulation of oncogene expression is associated with a selective or a preferential inhibition of tumour as compared to normal cell proliferation. Even though numerous studies attest the short-term in vitro efficacy of antisense oligodeoxynucleotides as inhibitors of tumour growth, the use of these compounds as therapeutic agents awaits a more rigorous demonstration of their long term effects and favourable pharmacological properties. PMID- 1286161 TI - A fundamental role for cell cycle regulation in the chemosensitivity of cancer cells? AB - The majority of clinically effective anticancer drugs inhibit some aspect of the machinery responsible for DNA replication and chromosome segregation. Drug action also arrests cells at defined points in the cell cycle called checkpoints. These checkpoints ensure that subsequent cell cycle events are inhibited until the inflicted damage is repaired. The fidelity of checkpoint control and susceptibility of cells to apoptosis while repair is underway may be important factors in the success of chemotherapy. We discuss these concepts and focus particularly on possible applications to improved antitumor therapy with DNA damaging agents. PMID- 1286162 TI - Induction of apoptosis--new targets for cancer chemotherapy. AB - Many anticancer agents induce an active cell death process, apoptosis, in sensitive tumour cells. Elucidation of molecular mechanisms underlying apoptosis may shed light on why some tumour cells survive chemotherapy, and may identify new targets for anticancer agents whose effects are not tightly linked to proliferative status. The signal transduction events which initiate apoptosis are unclear. A change in cytosolic calcium is generally assumed to be a key signal for apoptosis although the evidence for this is not conclusive. Other putative signal transducers which may modulate apoptosis are protein kinase C and cAMP. Genes which induce apoptosis in response to such signals are largely unidentified, but certain oncogenes, notably bcl-2, act to delay or suppress apoptosis in several cell types. PMID- 1286163 TI - Introduction: apoptosis in the immune system. PMID- 1286164 TI - Glucocorticoid-induced apoptosis in the thymus. AB - Destruction of thymus cells was one of the earliest observed properties of adrenal glucocorticoids. The cells affected are primarily immature, CD4/CD8 double-positive lymphocytes. This process has been clearly shown in vivo and in vitro to be apoptosis, as characterized by cell shrinkage, membrane alterations, nuclear collapse and chromatin fragmentation into oligonucleosomes. Glucocorticoid-induced thymocyte death requires new mRNA and protein synthesis. A beginning has been made in identifying the genes involved in thymocyte apoptosis. A case is made for the death of unselected thymocytes in vivo being regulated by endogenous glucocorticoids. PMID- 1286165 TI - Activation-induced apoptosis in lymphoid systems. AB - Lymphocytes become activated when antigen receptors on the cell surface are cross linked, or when they are exposed to agents that mimic this signal. Although such activation is usually associated with the production of immune mediators (e.g. antibodies, cytokines) and entry into the cell cycle, it can alternatively lead to death via apoptosis. This activation-induced apoptosis was first observed in developing lymphocytes and has been proposed as a mechanism for negative selection, by which immature cells with potential for autoreactivity are eliminated from the maturation pathway. Activation-induced apoptosis has also been observed in normal, mature lymphocytes under some conditions, and this may account for the phenomena of peripheral deletion, in which mature T cells are eliminated upon exposure to high doses of antigen. It may also be an important mechanism whereby CD4+ T cells are depleted in HIV+ individuals. Although the phenomenon of activation-induced apoptosis is not understood, recent studies have begun to implicate specific signal transduction pathways and gene products in the process. Among the latter is the c-myc proto-oncogene, which paradoxically can play an essential role in several forms of apoptosis, including that induced by activation of lymphocytes. PMID- 1286166 TI - Induction of apoptosis in cells of the immune system by cytotoxic stimuli. AB - Apoptosis is a physiological mode of death where the dying cell plays an active part in its own demise, which contrasts sharply with what is seen in necrosis. In the present paper I have shown that when cells of the immune system are exposed to a range of cytotoxic agents, such as the RNA synthesis inhibitor actinomycin D, the DNA polymerase inhibitor aphidicolin or the topoisomerase I inhibitor campthothecin, they rapidly undergo cell death via apoptosis. This is characterized by DNA fragmentation to yield the now hallmark ladder pattern of death by this mechanism. All of these agents are capable of inducing apoptosis irrespective of what phase of the cell cycle a cell is in. These studies also indicate that apoptosis can occur in immune cells without recourse to macromolecular synthesis. PMID- 1286167 TI - Apoptosis in cytotoxic T lymphocytes and their targets. AB - Cytotoxic T lymphocytes have been useful not only in understanding immune responses but also in providing valuable insights into the biology and mechanism of apoptosis. In this article two examples of apoptosis directly related to cytotoxic T lymphocyte biology are discussed. These are apoptosis of activated cytotoxic T cells as a result of antigen clearance and subsequent growth factor deprivation and apoptosis of target cells following interaction with cytotoxic T lymphocytes. PMID- 1286169 TI - Aesthetic and economic incentives for inlay and onlay restorations. PMID- 1286168 TI - The bcl-2 oncogene and apoptosis. AB - The bcl-2 oncogene is activated as a consequence of the t(14;18) chromosomal translocation in human follicular lymphomas. Bcl-2 functions to inhibit apoptosis in a variety of in vitro and in vivo experiments, suggesting interference with a central mechanism of apoptosis. The bcl-2 protein is associated with the inner mitochondrial membrane, however, the biochemical function of bcl-2 is unknown. Transgenic mice which overexpress bcl-2 provide evidence for bcl-2's role in memory B cells and thymic education as an intracellular survival factor. Additional regulators of apoptosis, such as the p53 tumor suppressor gene, may be altered in human cancers as one step in tumorigenesis. PMID- 1286170 TI - A pin-assisted retention technique for resin-bonded restorations. AB - The value of pins for auxiliary retention has been demonstrated many times. The use of pins with resin-bonded restorations allows for improved aesthetics and less tooth reduction while increasing resistance to dislodging forces. Clinical and technical procedures for resin-bonded bridges with pin-assisted retention are presented. PMID- 1286171 TI - Forced eruption for anterior aesthetics. PMID- 1286172 TI - Implant positioning for periodontal, functional, and aesthetic results. AB - Implant positioning requires the adherence to a very precise protocol in order to achieve the best periodontal, functional, and aesthetic results. In this article, the authors discuss the step-by-step procedure, including pre-implant study, transfer techniques, implant positioning, gingiva grafts, and post-implant hygiene. PMID- 1286173 TI - Chairside computer-generated ceramic restorations: the Cerec third generation improvements. AB - Cerec chairside computer-generated ceramic restorations have well passed a five year clinical observation period with convincing clinical success. The new system COS 2.1 allows an essentially automatic design of inlays, the construction of 3/4 and 4/5 cusp protection onlays, and individually-shaped aesthetic laminate veneers. The new E-drive grinding increases the machining capacity by factor 3 to 4, reduces edge roughness by 50%, and doubles machining precision. Cementation gap width at the cervical margin is 37-48 microns in normal-depth preparations and 54-76 microns in deep cavities. It is the purpose of this article to review the third generation improvements of this method. PMID- 1286174 TI - OSHA's occupational exposure to bloodborne disease standard. PMID- 1286175 TI - Implants and the lack of prosthetic readiness. PMID- 1286176 TI - Implant team: problems and solutions with osseointegrated implants. AB - The concept of an implant team, in which the implants are placed by the periodontist or oral surgeon and the prosthetic procedures are performed by a restorative dentist, provides a system of checks and balances. A team concept may minimize the potential for failure and provide an environment of cooperation that can lead to even better success, with a minimum of difficulty and fewer complications. In this author's experience, a wide variety of avoidable problems may become evident in the implant restorative area. This article examines some of the more common problems and provides suggestions for solutions. PMID- 1286177 TI - Root coverage: a comparison of techniques: the free gingival graft versus the subepithelial connective tissue graft. AB - This past decade has seen the goals of periodontal surgery undergo much refinement. Gingival recession is a frequent concern to both the clinician and patient. Regeneration of the lost gingival tissues is now an achievable goal. This article reviews and compares two techniques currently employed for predictable root coverage. PMID- 1286178 TI - Aesthetic all-porcelain anterior restorations. AB - The translucence of all-porcelain restorative materials very closely resembles that of natural teeth, thereby enabling the nearest possible emulation of natural teeth. Because of this quality and the suitability for bonding, all-porcelain has become the choice material for anterior jackets, three quarters, and veneers. In this article, the author uses actual cases to substantiate and illustrate her evaluation. PMID- 1286179 TI - Interim report of Sino-Monica-Beijing for the years 1985-1989. AB - Interim results of Sino-Monica-Beijing for the 5 year period 1985-1989 are reported. The cardiovascular disease (CVD) risk factors increased between the surveys carried out in 1984-1985 and 1988-1989, especially blood cholesterol and body mass index. PMID- 1286180 TI - Outcome among untreated hypertensives in the general population in Taiwan. AB - The outcome of untreated hypertension was investigated in a population of 17,713 persons in southern Taiwan who were aged 15 or over when they had taken part in a blood pressure survey in 1963. In the 27-year follow-up period, 55.8% of the overall mortality was comprised of those who were found to be hypertensive (as defined by WHO) in 1963, 31.3% by borderline hypertensives, and 22.6% by normotensives. The 27-year mortality rate due to stroke was much higher in hypertensives than in normotensives (11.4% vs 1.8%, respectively). The 5-year survival rates for mild, moderate and severe hypertensives were 89.9%, 82.7% and 72.3%, respectively, and the 20-year rates were 60.2%, 37.2% and 25.2%, respectively. The causes of death were also recorded: among hypertensives, stroke accounted for 23.2% of all deaths of known cause, cancer 20.5%, cardiovascular disease 21.7%, respiratory disease 11.8%, and other causes 22.9%. From the results, it is concluded that obvious differences in mortality and cause of death exist between untreated hypertensives and normotensives. PMID- 1286181 TI - Therapeutic effect of andriol on serum lipids and apolipoproteins in elderly male coronary heart disease patients. AB - The elevated estradiol/testosterone (E2/T) ratio had been proved to be a risk factor for coronary heart disease (CHD) in elderly males and to exert an adverse effect on lipid metabolism. We conducted a randomized cross-over study to determine the effect of Andriol, a new androgenic preparation, on plasma lipids and apolipoproteins. The results showed a significant difference in most parameters between patients receiving Andriol and the control group: in the former, serum T level was elevated significantly (P < 0.001), E2 level was unchanged (P > 0.05) and the E2/T ratio was reduced (P > 0.05). Blood levels of total cholesterol (TC) and triglyceride (TG) were lowered dramatically (P < 0.001) and high density lipoprotein cholesterol (HDL-ch) was raised (P < 0.05), but apolipoprotein-AI (APO-AI) and B (APO-B) levels remained unchanged. No obvious side effect was observed in those who took Andriol. PMID- 1286182 TI - The effect of IH764-3 on fibroblast proliferation and function. AB - The effect of IH764-3, a potent component isolated from Salvia miltiorrhiza, on the proliferation and function of cultured fibroblasts was studied. It was found that the fibroblast growth curve had a dose-dependent relationship with IH764-3 concentration. The incorporation of 3H-TdR and 3H-proline into fibroblasts was significantly inhibited by IH764-3, and calmodulin, fibronectin and thrombospondin contents in the test group were obviously lower than those in the control group. Flow cytometry showed that in the IH764-3-treated group, the percentage of cells in G0/G1 phase was higher than that in the control. Electron microscopic observation (TEM and SEM) showed that in the treated group, collagen secretion was decreased. All of these results indicate that IH764-3 exerts a direct inhibitory effect on fibroblast proliferation and affects their ability to synthesize collagen. PMID- 1286183 TI - [14C]-glucose metabolism of Oncomelania snails. AB - To elucidate the importance of glucose metabolism in Oncomelania snails, uniformly labelled D (14C)-glucose [(U-14C)-glucose] has been used as a tracer for observing glucose uptake, incorporation into macromolecules and the activity of enzymes involved in its metabolic pathway. Radioactivity of Oncomelania increased with time of exposure (3, 6, 12 and 24 h) to [(U-14C)-glucose] solution. In snails treated with 2 ppm bromoacetamide for 24 h, the radioactivity of soft tissues was markedly less than that of normal snails. Oncomelania can synthesize glycogen from absorbed glucose, and the absorbed (U-14C)-glucose may be incorporated into nucleic acid, protein and lipid, with 14CO2 excreted as an end metabolic product. 6-phosphoglucose dehydrogenase and 6-phosphogluconate dehydrogenase activities were demonstrated by the reduction of NADP and determination of 14CO2 from (1-14C)-glucose, respectively. The results indicate that there exists a phosphopentose pathway in Oncomelania. PMID- 1286184 TI - The role of endotoxin in the pathogenesis of experimental multiple system organ failure: a preliminary report. AB - In this study, an animal model of multiple system organ failure (MSOF) in rabbits, engendered by feeding E. coli prior to severe hemorrhagic shock, was used for the purpose of investigating 1) the relationship between lipopolysaccharide (LPS) and MSOF, and 2) the effectiveness of Re-LPS antiserum in preventing MSOF. The results showed that endotoxemia occurred very early, and its degree correlated well with that of organ dysfunction. Re-LPS antiserum administration abated the toxic effects and lowered the incidence of MSOF. These results suggest that sequential analysis of circulating LPS levels may be useful for the early diagnosis of MSOF, and that gut-derived endotoxin might play an important role in the pathogenesis of experimental MSOF. PMID- 1286185 TI - The stress distribution of the lumbar spine and disc degeneration. AB - A three-dimensional finite element model of the lumbar motion segment was developed to study the effect of disc degeneration upon stress distribution in the lumbar spine. The results showed that after degeneration of the intervertebral disc, the stress distribution and load transmission of the lumbar spine are significantly changed. It is concluded that these changes provide a biomechanical basis for understanding the etiology of spinal canal stenosis and nerve root entrapment. PMID- 1286186 TI - How the degenerate signal is recognized and delivered in the course of protein translocation across biological membranes. AB - Protein translocation across a membrane is generally directed by a degenerate signal peptide encoded in the nascent polypeptide chains. Effective signal recognition and the subsequent traversal of the polypeptide chain through the membrane are ensured by the mechanism of cotranslational translocation and/or by chaperone molecules which universally bind to nascent polypeptides and keep them under-structured and translocation-competent. In order to decipher the degenerate signal with a high degree of fidelity, the cells seem to have evolved a multistep signal recognition and relay mechanism, by which a weak, less-specific interaction between individual signal peptides and a defined signal recognition factor can take place, while the highly specific signal delivery can be achieved by only allowing the correct, effective signals to pass through all check-points along the relay cascade. In addition, a "double recognition" and energy-dependent "proof-reading" mechanism may be involved in single steps of such weak-bond interactions. PMID- 1286187 TI - Fever, chest pain, left abdominal pain, shock. PMID- 1286188 TI - Hemophilic blood cyst--a case report. AB - We report a case of hemophilic blood cyst in a patient with human immunodeficiency virus (HIV) infection. The pathogenesis, diagnosis and treatment are discussed, and neither inflammatory changes nor pathological cells were seen in the numerous histological sections obtained surgically. PMID- 1286189 TI - A new immunohistochemical method to demonstrate DNA-synthesizing cells in human stomach cancer tissues. PMID- 1286190 TI - [Difficulties in communication with dying patients]. PMID- 1286191 TI - [Ethical discussions in professional health care journals]. PMID- 1286192 TI - [Care of severely ill and dying patients]. PMID- 1286193 TI - [A report on death with dignity]. PMID- 1286194 TI - Influence of storage on signal transduction pathways and platelet function. AB - The use of platelet concentrates in prophylactic and therapeutic transfusions has increased considerably. The design of suitable storage bags and improvements in procurement, processing, and storage practices have contributed significantly to the quality of stored platelets and their increased shelf life. There continues to be activation of platelets during procurement of blood, shipment, processing, and storage. By using appropriate preventive measures, inhibitors of platelet activation and protectants, platelet activation can be minimized. Although platelets seem to recover from initial activation and function normally, their in vitro response varies depending on the degree of activation occurring during preparative procedures. By and large, response to weak agonists diminishes rapidly during aging in storage. Further studies are essential to determine the reason for the development of this acquired defect. The normal response of stored platelets to a potent agonist such as thrombin suggests that signal generation and transduction mechanisms are not significantly compromised during storage. Epinephrine-mediated membrane modulation may contribute significantly to their improved in vivo performance during transfusions. PMID- 1286195 TI - Contribution of perfusion techniques to the evaluation of the hemostatic effectiveness of platelet concentrates. AB - Perfusion systems allowing the morphometric analysis of platelet interactions with vessel subendothelium under flow conditions have been applied to evaluate the quality and function of stored platelets. Studies performed in vitro indicate that despite the existence of storage lesions, platelets in concentrates stored for up to 5 days retain their ability to interact with the subendothelium. Perfusion studies ex vivo with nonanticoagulated blood from anemic thrombocytopenic patients have shown the critical hemorrheological role of red blood cells facilitating platelet interactions with subendothelium. Similar studies performed on severely thrombocytopenic patients who received transfusions of platelets stored at 4 degrees C indicate that incompletely viable platelets can contribute to primary hemostasis through procoagulant mechanisms. The latter results suggest that storage lesions which contribute to impairment of platelet function may result in enhancement of platelet procoagulant activities. Perfusion techniques have contributed to the evaluation of the hemostatic effectiveness of platelet concentrates. These techniques will provide a useful model to test the impact of new storage technologies on platelet hemostatic function. PMID- 1286196 TI - Effect of additive solutions on platelet biochemistry. AB - Use of a synthetic medium for resuspension and storage of platelets has several advantages. In addition to the opportunity to save plasma, the use of a synthetic medium offers better possibilities for obtaining platelet products by automatic component processing in a more cost-effective and convenient manner. A synthetic medium also has the potential to avoid transfusion reactions caused by noncompatible plasma proteins and to improve platelet quality, which will lessen the number of units needed in transfusion. Platelets produce a substantial amount of lactic acid by metabolism of glucose. Thus, risk of pH fall is a major problem which platelet additive solutions must address. Two approaches have been used: (1) use of a glucose-free medium, and (2) use of a glucose-containing medium with a buffer system to neutralize the production of lactic acid. Using various synthetic media described in the literature, studies described in this paper suggest that some glucose is needed in the final suspending medium in order to obtain satisfactory maintenance of platelet quality during 5 days of storage. With the presence of acetate in the additive solution, platelet respiration is increased and glycolysis substantially decreased; therefore, with 10-20% of CPD plasma carryover, sufficient glucose may be present in the final suspending medium to last for 5 days of storage. In addition, phosphate in the additive solution markedly enhances platelet glycolysis, and inhibitors of platelet activation reduce platelet metabolic activity and improve platelet viability and function. PMID- 1286197 TI - Review: the platelet storage lesion: possible role of plasticizers? PMID- 1286198 TI - Ultrastructural changes in stored platelets. AB - A wide variety of lesions develop in blood platelets stored in vitro for long periods of time. Most of them reflect activation and damage caused by lack of gas exchange across the wall of the container and a fall in pH below 6. Newer bags facilitate O2/CO2 exchange and maintain a neutral pH. As a result, most of the lesions reflecting acidic damage or destruction have disappeared. Some storage lesions persist, however. Formation of platelets resembling doughnuts occurs in the first 24 or 48 hours after collection and concentration. They are infrequent in currently used bags. Giant alpha granules resulting from fusion of normal sized organelles, however, are not rare. They appear as early as 4 to 5 days, even under the best conditions, and increase in frequency up to 14 days. The basis for their development remains obscure. PMID- 1286199 TI - The role of membrane lipid in the platelet storage lesion. AB - Because of their hemostatic and structural importance and their chemical and physical lability, membrane lipids are likely to be involved in the development of the platelet storage lesion. Chemical analysis using the new method of high performance liquid chromatography with laser light scattering detection (HPLC LLS) reveals platelet lipid to be composed of more than 22 individual components, the most abundant of which are phosphatidylcholine (PC), phosphatidylethanolamine (PE), cholesterol (C), sphingomyelin (SM), phosphatidylserine (PS), and phosphatidylinositol (PI). Surprisingly, an asymmetric distribution of these lipids is maintained in the resting platelet with PS concentrated in the inner leaflet of the plasma membrane. The exposure of PS may be important in platelet activation because of its powerful procoagulant effect. Studies of the effect of blood bank storage on platelet lipid composition have repeatedly shown a steady loss of all components, which may be temperature dependent. Studies of platelet factor 3 activity and flow cytometry of stored platelets have revealed the lipid is lost through the process of microvesiculation. Coupled to this storage induced depletion of platelet lipid is a loss of more than half of the potential capacity of lipid-dependent platelet functions by day 5. The most likely underlying mechanism for this loss of lipid mass and functional capacity is lipid peroxidation, a process that could be blocked with antioxidants. Lipid peroxidation may also interfere with other membrane constituents such as glycoprotein IIb/IIIa and the aminophospholipid-specific translocase. Thus, lipid peroxidation should be a major focus in studies aimed at preventing or reversing the platelet storage lesion. PMID- 1286200 TI - Identification of yolk platelet-associated hydrolases in the oocytes of Rhodnius prolixus. AB - The yolk platelets from Rhodnius prolixus, a blood-sucking bug, are composed mostly of vitellin and here are shown to contain at least two hydrolytic enzymes, a phosphatase and a cathepsin D-like proteinase. Both the proteinase and the phosphatase have an acid pH optimum. No hydrolytic activity was observed under alkaline or neutral conditions. Among several proteinase inhibitors tested, only pepstatin could abolish vitellin breakdown in vitro. The proteinase appears to be bound to the yolk platelet membranes. The phosphatase activity, using p nitrophenyl phosphate as substrate, was enhanced after disruption of the platelet membrane by Triton X-100. This activity could be inhibited by tartrate but not by p-cloromercuribenzoate. PMID- 1286201 TI - The effect of pinealectomy on circadian plasma melatonin levels in house sparrows and European starlings. AB - We determined 24-hr plasma melatonin profiles in intact, sham-pinealectomized, and pinealectomized European starlings (Sturnus vulgaris) and house sparrows (Passer domesticus) in a light-dark (LD) cycle and in constant darkness (DD). In the intact and sham-pinealectomized birds of both species, a melatonin rhythm was found, with low levels during the day and high levels during the night. Pinealectomy abolished the nighttime peak of melatonin in both species; hence, levels were low at all times sampled. This uniform response of plasma melatonin to pinealectomy contrasts with the differential response of circadian activity rhythms to pinealectomy for these two species. In DD, locomotor activity in pinealectomized house sparrows is usually arrhythmic, whereas in starlings a rhythm usually persists. This suggests that in the latter species free-running circadian rhythms are not necessarily dependent on a rhythm in plasma melatonin. The same is true for the synchronized activity rhythm observed in pinealectomized birds of both species in LD, as well as for the damped rhythm that persists in pinealectomized house sparrows following an LD-to-DD transfer. The results are consistent with the hypothesis that the pineal and its periodic output of melatonin constitute only one component in a system of at least two coupled pacemakers. They also suggest that there are species differences in the relative role played by the pineal and other pacemakers in controlling circadian rhythms in behavior. PMID- 1286202 TI - Circadian feeding and locomotor rhythms in pigeons and house sparrows. AB - Feeding and locomotor activities were measured simultaneously in homing pigeons (Columba livia) and house sparrows (Passer domesticus). Feeding, as well as locomotor activity, was found to be regulated by a circadian clock in both of these species. Implantation of melatonin-filled capsules or exposure to constant light abolished feeding and locomotor rhythms in both species. Removal of the pineal gland from pigeons did not abolish either rhythm, whereas pinealectomy abolished both feeding and locomotor rhythms in house sparrows. Although feeding rhythms were generally more robust than locomotor rhythms in both of these species, different feeding and locomotor free-running periods were not observed within any individual pigeon or house sparrow. These results are consistent with the hypothesis that each of these species has a single pacemaker that regulates the timing of feeding and locomotor activity, but they do not rule out the possibility that separate clocks regulate these behaviors. PMID- 1286203 TI - Light pulses induce "singular" behavior and shorten the period of the circadian phototaxis rhythm in the CW15 strain of Chlamydomonas. AB - While measuring action spectra for phase-shifting the circadian clock of Chlamydomonas, we observed that light pulses started near the phase response curve (PRC) "breakpoint" caused a reduction of the amplitude of the phototactic rhythm and two unexpected effects: (1) nonmonotonic fluence response curves (FRCs), and (2) shortening of the period of the subsequent free-running rhythm. The reduction of the rhythm's amplitude is dependent upon both the fluence and wavelength of the light pulse. The results are consistent with the amplitude being dependent upon the perceived "strength" of the stimulus, and with the nonmonotonic FRCs and reduced amplitude reflecting a light-induced change of the pacemaker's state variables to a region of the phase plane close to the "singularity." The period change that is evoked by single stimuli exhibits novel characteristics: large changes in period and a phase specificity that correlates with "singular" behavior. These period changes also appear to be a function of the stimulus strength, but indirectly; the magnitude of the period change is most strongly correlated with the magnitude of the light-induced phase shift. These results are interpreted in the context of limit cycle models of circadian clocks, and are used to suggest new tactics for measuring action spectra of light-induced clock resetting. PMID- 1286205 TI - Sleep and waking have a major effect on the 24-hr rhythm of cortical temperature in the rat. AB - The relationship between the time course of cortical temperature (TCRT) and sleep wake alternation was investigated by correlation analyses and a computer simulation. The data for these analyses were collected in 10 rats in a 4-day experiment (LD 12:12), during which vigilance states and TCRT were determined for consecutive 8-sec epochs. On day 1 baseline recordings were obtained; on day 2 the animals were sleep-deprived; and days 3 and 4 served as recovery days. The correlation analyses revealed that the alternation of sleep and waking accounted for 84% of the variance of TCRT when analyzed for hourly intervals. The residual variance displayed a 24-hr periodicity with an amplitude of 0.15 degrees C. Similar results were obtained in a separate data set of a 2-day experiment, which consisted of a baseline day (LD 12:12) and a day with constant darkness. The periodicity of the residual variance of TCRT can therefore be considered to represent the circadian temperature rhythm not masked by the vigilance states. In the computer simulation, the time course of TCRT was simulated on the basis of the sequence of the vigilance states with an 8-sec time resolution. It was assumed that TCRT increases during waking and rapid-eye-movement (REM) sleep according to an exponential saturating function, and decreases exponentially during non-REM sleep. The simulations could account for 88-93% of the variance of TCRT. We conclude that in the rat, the major part of the variation of TCRT is accounted for by vigilance states, whereas a minor part can be attributed to a direct effect of the circadian pacemaker. PMID- 1286204 TI - Photoperiod modulates pubertal shifts in behavioral responsiveness to testosterone. AB - This study examined the effect of photoperiod on pubertal maturation of steroid dependent reproductive behaviors in male European ferrets (Mustela putorius furo). In the first experiment, levels of neck gripping, mounting, and pelvic thrusting in gonadally intact prepubertal (PRE) ferrets were compared with those of adults that had undergone puberty either while housed in short days (8 hr light/16 hr darkness per day; SD), or after transfer from SD to long days (18 hr light/6 hr darkness per day; LD) at 12 weeks of age. Both LD and SD adults demonstrated significantly greater amounts of neck gripping and mounting than PRE males. In addition, a significantly greater proportion of adults in both SD and LD displayed at least one incidence of the three behaviors compared to PRE ferrets. There were no statistically significant differences in behavior of the gonadally intact LD and SD adults. In the second experiment, dose-response curves for behavioral responses to subcutaneous injections of 0, 0.5, 1.25, 2.5, 5, and 10 mg/kg testosterone propionate (TP) in oil were generated in castrated PRE, SD, and LD males. The lowest dose of TP elicited significantly greater amounts of all three behaviors in LD adults than in PRE ferrets. In addition, levels of mounting and thrusting elicited by the lowest dose of TP were significantly greater in LD adults than in SD adults. These data indicate that pubertal activation of male sexual behavior in male ferrets is accompanied by a pubertal increase in responsiveness to the behavioral effects of testosterone. Furthermore, the degree of behavioral responsiveness of adult ferrets to testosterone is modulated by environmental photoperiod experienced during reproductive maturation. PMID- 1286206 TI - Behavioral inhibition of circadian responses to light. AB - Circadian locomotor rhythms in rodents may be synchronized by either photic or nonphotic events that produce phase shifts of the rhythm. Little is known, however, about how these two types of stimuli interact to produce entrainment. The well-characterized circadian photic response of the golden hamster was examined in situations where a short light pulse and locomotor activity, a nonphotic event, occurred simultaneously. Light-induced phase advances were attenuated when animals were active during light exposure. The results show that circadian responses to light depend upon the environmental situation in which the light is given, and call into question the implicit assumption in circadian rhythm research that phase shifting and entrainment to light-dark cycles depend simply on photic activation of well-known retinofugal pathways. Moreover, since light therapy is becoming an important component in the treatment of circadian based disorders in humans, the results emphasize the need for evaluation of the behavioral aspects of light therapy protocols. PMID- 1286207 TI - Electrospray mass spectrometry of Malayan pit viper (Calloselasma rhodostoma) venom. AB - A high-performance liquid chromatography protocol has been developed for the analysis of snake venoms. This system has been used to isolate eight fractions from Malayan pit viper (Calloselasma rhodostoma) venom. The fractions have been analysed using electrospray mass spectrometry. A number of major components were found with masses ranging from 13,670 to 22,750 Da. PMID- 1286208 TI - A novel derivatization method for peptides to increase sensitivity and backbone fragmentation in liquid secondary-ion mass spectra. AB - Derivatization is used to increase both negative-ion sensitivity and positive-ion sequence information in the liquid secondary-ion mass spectra (LSIMS) of a series of peptides. The derivatization method involves acylation with pentafluorobenzoyl fluoride in a single-step reaction, and the reaction mixture is applied directly to the probe tip for analysis. Acylation takes place at the unprotected N terminus, tyrosine, and lysine. The derivatives exhibit increased signal-to-noise ratio for [M-H]- ions, especially where there is not already an acidic amino acid residue in the peptide. In positive-ion LSIMS, the N-terminal group acts to retain the charge at the N-terminus, simplifying the fragmentation by producing N terminal fragment ions. It also increases positive-ion fragmentation, sometimes very dramatically, making sequence determination more straightforward. The simplicity of the process, together with the enhancements it provides, make this a generally useful method for obtaining peptide structural information. PMID- 1286209 TI - Application of fast-atom bombardment mass spectrometry for sequencing of a hemoglobin fragment, naturally occurring in human cerebrospinal fluid. AB - Recent studies have revealed the presence of a new group of opioid peptides, the hemorphins, in the human pituitary as well as in human cerebrospinal fluid. The hemorphins are structurally related to sequence segments residing in the beta, delta, gamma or epsilon-chains of hemoglobin. In this study we have applied fast atom bombardment mass spectrometry (FAB-MS) to elucidate the sequence of a hemorphin fragment isolated from the cerebrospinal fluid of patients with cerebrovascular bleedings. The FAB-MS was used in conjunction with carboxypeptidase Y digestion and results indicated that this procedure proved to be a powerful tool for rapid sequence determination. The recovered peptide was thus found to be identical with the sequence 32-41 of the above mentioned hemoglobin chains. PMID- 1286210 TI - Determination on the microscale of plasmatic lactic acid as its t butyldimethylsilyl derivative by stable-isotope dilution using capillary gas chromatography/mass spectrometry. AB - A new sensitive and precise method for the determination of lactic acid in plasmatic microsamples (50 microL) has been developed. Lactic acid was directly extracted from plasma by ethyl acetate in acidic conditions, and analysed as its di-t-butyldimethylsilyl derivative by capillary gas chromatography/electron impact mass spectrometry (GC/MS). The internal standard was a previously synthesized deuterated compound, 3-[2H]-(2R)-lactic acid. The method gives good reproductibility and precision, the overall standard deviation being better than 3%. The GC/MS assay was in good agreement with the enzymatic determination. PMID- 1286211 TI - N-cadherin transcripts in Xenopus laevis from early tailbud to tadpole. AB - Cadherins are Ca(++)-dependent cell adhesion molecules which play a key role in morphogenesis and histogenesis. Two mRNAs clones (8 and 9) corresponding to two N cadherin pseudo-allelic genes are present in Xenopus laevis. We report here that these transcripts share a highly homologous coding region but diverge in the non coding region. We have determined the pattern of N-cadherin expression at the mRNA level by in situ hybridization with a riboprobe complementary to the EC5 domain of Xenopus N-cadherin clone 8. This part of the sequence is the least conserved in the cadherin gene family, minimizing the risk of cross-hybridization to other cadherins. N-cadherin transcripts are not detectable in the first stages of development. Expression first appears in the neural plate and reaches its maximum level in the CNS at tailbud stage. From early tadpole, it diminishes, so that a very weak signal is detected in the premetamorphic frog brain. N-cadherin expression is not uniform within the CNS, with some areas such as the roof of the rhombencephalon and the olfactory bulbs expressing higher levels of the transcripts. N-cadherin is present in several mesodermal derivatives such as the notochord, the pronephros, and the heart. It is, however, virtually absent from the myotomes and appears in skeletal muscles at later stages of differentiation. All placodes express high levels of N-cadherin. The non-neural ectoderm and the endoderm are always negative. In the brain and the heart, high levels of hybridization are observed with probes corresponding to both copies of the N cadherin pseudo-allelic genes in their 5' non-coding region, indicating that both alleles are transcribed. PMID- 1286212 TI - Diffusion or autocatalysis of retinoic acid cannot explain pattern formation in the chick wing bud. AB - We have collected several experimental data of pattern duplications due to the ZPA transplantation or application of retinoic acid on the developing chick limb bud. We have compared these data with the predictions of models based on diffusion or autocatalysis of retinoids. It turns out that these models cannot comprehensively explain the data. More specifically, retinoic acid cannot be either diffusing from a ZPA source or participate in an autocatalytic gradient formation. PMID- 1286213 TI - EMA: a developmentally regulated cell-surface glycoprotein of CNS neurons that is concentrated at the leading edge of growth cones. AB - To identify cell-surface molecules that mediate interactions between neurons and their environment during neural development, we used monoclonal antibody techniques to define a developmentally regulated antigen in the central nervous system of the mouse. The antibody we produced (2A1) immunolabels cells throughout the central nervous system; we analyzed its distribution in the developing cerebral cortex, where it is expressed on cells very soon after they complete mitosis and leave the periventricular proliferative zone. Expression continues into adult life. The antibody also labels the epithelium of the choroid plexus and the renal proximal tubules, but does not label neurons of the peripheral nervous system in the dorsal root ganglia. In dissociated cell culture of embryonic cerebral cortex, 2A1 labels the surface of neurons but not glia. Immunolabeling of neurons in tissue culture is particularly prominent on the edge of growth cones, including filopodia and the leading edge of lamellipodia, when observed with either immunofluorescence or freeze-etch immunoelectron microscopy. Immunopurification with 2A1 of a CHAPS-extracted membrane preparation from brains of neonatal mice produces a broad (32-36 kD) electrophoretic band and a less prominent 70 kD band that are sensitive to N-glycosidase but not endoglycosidase H. Thus the 2A1 antibody recognizes a developmentally regulated, neuronal cell surface glycoprotein (or glycoproteins) with complex N-linked oligosaccharide side chains. We have termed the glycoprotein antigen EMA because of its prominence on the edge membrane of growth cones. EMA is similar to the M6 antigen (Lagenaur et al: J. Neurobiol. 23:71-88, 1992) in apparent molecular weight, distribution in tissue sections, and immunoreactivity on Western blots, suggesting that the two antigens are similar or identical. Expression of EMA is a very early manifestation of neuronal differentiation; its distribution on growth cones suggests a role in mediating the interactions between growth cones and the external cues that guide them. PMID- 1286214 TI - Fogarty's life, Fogarty's contributions. PMID- 1286215 TI - Placebo. PMID- 1286216 TI - Tuberculosis. PMID- 1286217 TI - Health for peace: John E. Fogarty's vision American leadership in health care and international biomedical research. A 25th year perspective. PMID- 1286218 TI - Weighing community and individual needs: use of placebos in clinical testing. PMID- 1286219 TI - Recent trends in clinical immunology. PMID- 1286220 TI - Questionnaire surveys of cases of tick bite and Lyme borreliosis in hunters in Hokkaido with reference to detection of anti-Borrelia burgdorferi antibody. AB - An epidemic of Lyme borreliosis on Hokkaido island, Japan, was surveyed by questionnaire in 587 hunters. The 308 returns (52.4%) revealed episodes of tick bite (usually 2 or more) in 210 cases. Skin rashes appeared in 164 cases. Associated itching, pain, etc., but not skin rash, were more frequent after 2 or more tick bite. Previous determinations of anti-Borrelia burgdorferi antibody titers in these subjects and in controls suggested an association with outdoor activities other than hunting, and among 33 cases of dermatological symptoms and 23 of articular symptoms, 4 and 2, respectively, were antibody-positive. Most of these antibody-positive subjects had suffered tick bite at least twice, but had had no antibiotic treatment. Three subjects with joint disorders were antibody positive. These findings suggested that the many hunters exposed to Borrelia burgdorferi frequently carried latent infections, and that some had latent form of arthritis, dermatitis and other disorders. PMID- 1286221 TI - Higher cortical dysfunction, antiphospholipid antibodies and neuroradiological examinations in systemic lupus erythematosus. AB - We performed neuropsychological tests to investigate higher cortical dysfunction in 21 patients with systemic lupus erythematosus (SLE). We also measured antiphospholipid antibodies (APA), performed brain computed tomography (CT), and obtained a single photon emission CT (SPECT) to measure regional cerebral blood flow (rCBF) in order to elucidate a possible relationship between APA and higher cortical dysfunction. Higher cortical dysfunction was noted in as many as 16 (76%) out of 21 cases. APA were positive in 8 (38%) out of 21 cases. Although the relationship between APA and higher cortical dysfunction was not significant, patients positive for lupus anticoagulant (LA) were found to have higher cortical dysfunction. Brain CT revealed at least one abnormality in 6 cases (29%) but none had a localized lesion, SPECT disclosed a reduced rCBF in 9 cases (43%). The findings on brain CT and SPECT were unrelated to higher cortical dysfunction. PMID- 1286222 TI - Cardiovascular and sympathetic nervous responses to mental stress in hyperthyroid patients. AB - We measured the cardiovascular and sympathetic nervous responses to mental stress in subjects with hyperthyroidism. Ten hyperthyroid subjects and 10 age- and sex matched normal subjects performed mental arithmetic. At rest, the heart rate was higher in hyperthyroid subjects than in normal subjects, but systolic blood pressure, plasma norepinephrine, and epinephrine concentrations did not differ between the two groups. Systolic blood pressure and heart rate during stress, and the changes in blood pressure and in plasma epinephrine concentration from rest to stress, were higher in hyperthyroid subjects than in normal subjects. Therefore, cardiovascular and adrenal responses to mental stress were abnormally high in subjects with hyperthyroidism. PMID- 1286223 TI - Response to oral corticosteroid in patients with chronic obstructive pulmonary disease. AB - We studied the effect of 30 mg of prednisolone on 29 Japanese patients with chronic obstructive pulmonary disease (COPD). The mean value of the baseline forced expiratory volume in one second (FEV1; mean +/- SEM) was 1.14 +/- 0.12 l (46.9 +/- 3.9% pred) and the FEV1 following the steroid trial was 1.30 +/- 0.12 l (53.7 +/- 4.3% pred). Post-trial FEV1--baseline FEV1/predicted FEV1 was 6.8 +/- 1.9%. Five patients (17%) had more than a 15% increase in FEV1 as a percentage of predicted FEV1. Post-trial FEV1/baseline FEV1 was 117.3 +/- 4.3%, and 12 patients (41%) had more than a 20% increase in FEV1 after the trial. Acute bronchodilator response to beta-agonist correlated positively with the response to corticosteroid. Baseline spirometries, blood eosinophil counts, serum IgE levels, sputum eosinophil counts, family history of asthma, and history of paroxysmal dyspnea did not vary across responders and non-responders. Patients with severe COPD should be treated to achieve the best possible pulmonary functions indicated by a steroid trial within the limit of acceptable levels of adverse effects. PMID- 1286224 TI - Malignant lymphoma in the mesentery with immune thrombocytopenia. AB - A 69-year-old man was referred to our hospital for further evaluation of an abdominal mass. After admission, he was suspected of having a malignant mesenteric tumor. Laboratory data disclosed thrombocytopenia with increased levels of platelet-associated immunoglobulin G. On surgery, the tumor involved the ileal mesentery, invading the urinary bladder and mucosal surface of the terminal ileum. The diagnosis of mesenteric lymphoma with immune thrombocytopenia was made. Complete remission was obtained after surgery and the subsequent three courses of combination chemotherapy. However, thrombocytopenia still persisted. This rare presentation is discussed with a review of the available literature. PMID- 1286225 TI - Inherited heterozygous protein C deficiency and dysfunctional protein S with recurrent venous thrombotic diseases: a study of three generations of a Japanese family. AB - We describe a rare occurrence of a family affected with venous thrombosis, exhibiting a protein C (PC) deficiency and dysfunctional protein S (PS). The propositus and his father developed recurrent venous-thrombosis. Their PC deficiency was characterized by low levels of both antigen and activity, and their dysfunctional PS was suggested by low PS activities despite the presence of normal free PS antigen. Over three generations, six family members had a PC deficiency, and three had both a PC deficiency and a dysfunctional PS. The mode of inheritance of PC deficiency appears to be autosomal dominant. PMID- 1286226 TI - Isolated IgA deficiency accompanied by autoimmune thyroid disease. AB - Selective immunoglobulin (Ig) A deficiency is reported to occur in 1 in 16,000 in Japan and has been reported to be complicated with various autoimmune diseases. A 49-year-old woman was diagnosed as having autoimmune thyroid disease. Her serum IgA, IgM and IgG were revealed to be 4.1, 154 and 1930 mg/dl, respectively. Severe skin eruption which occurred with 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU), was relieved by reducing MMI to 15 mg/day and administering anti-allergic drugs. Although the influence of IgA deficiency on autoimmunity and allergy still remains unclear, this is a report of IgA deficiency associated with autoimmune thyroid disease. PMID- 1286227 TI - Hypersensitivity pneumonitis induced by Shiitake mushroom spores. AB - Hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores was demonstrated in a 38-year-old woman. Symptoms of cough, nausea and malaise, and clinical findings of cyanosis, bibasilar crackles, reduced lung volumes, hypoxemia, leukocytosis, elevated ESR, positive C-reactive protein, and bilateral diffuse reticulonodular shadows on chest roentgenogram improved after the patient was removed from exposure. Alveolitis was demonstrated by transbronchial lung biopsy, as well as an increase in lymphocytes in bronchoalveolar lavage. Serum precipitins and specific IgG antibodies to an extract of Shiitake mushroom spores, but not to other common molds or mushroom body, were detected in serum. Provocative inhalation test with the extract of mushroom spores caused the same clinical symptoms and signs as experienced in the workroom. This is the first report of typical hypersensitivity pneumonitis induced by Shiitake mushroom spores. Mushroom spores as well as thermophilic actinomycetes must be considered a causative agents for mushroom worker's lung. PMID- 1286228 TI - Increased interleukin-6 activity in cardiac myxoma with mediastinal lymphadenopathy. AB - We report a case of cardiac myxoma with mediastinal lymphadenopathy which seems to be a very rare feature. Laboratory examination revealed high level of interleukin-6 (IL-6) activity in serum. Interestingly, after removal of cardiac myxoma, mediastinal lymphadenopathy disappeared on the chest CT and the level of serum IL-6 was decreased. These findings suggest that IL-6 which was probably derived from myxoma, may have played an important role in the development of lymphadenopathy. PMID- 1286229 TI - Brain tumor in a pedigree of cancer family syndrome. AB - Brain tumors have not been previously described as a cancer found in cancer family syndrome (Lynch Syndrome II). Astrocytoma found in the 24-year-old son of a proband of cancer family syndrome with an unusual aggregation of transitional cell cancer is reported. The possibility of brain tumors as a rare spectrum of neoplasms in cancer family syndrome is discussed. PMID- 1286231 TI - Renal artery aneurysm: the significance of abdominal bruit and use of color Doppler. AB - A case of renal artery aneurysm is presented. The patient had no hypertension and no signs of arteriosclerosis obliterans or aortitis syndrome, except for abdominal bruit. A saccular aneurysm, 1 cm in diameter, was demonstrated by two dimensional and color Doppler ultrasound and documented by angiography. The aneurysm was embolized by a steel coil. The abdominal bruit, though uncommon, is a very important bed-side sign of renal artery aneurysm, if the patient exhibits no arteriosclerosis obliterans or aortitis syndrome. Ultrasound Doppler is very useful in screening for aneurysm. PMID- 1286230 TI - Hashimoto's thyroiditis in HTLV-I carriers. AB - We describe two HTLV-I virus carriers who have biopsy-proven Hashimoto's thyroiditis. The first patient, a 64-year-old female, has had goiter and hypothyroidism since the age of 56. The second patient, a 66-year-old male, developed hyperthyroidism and goiter at the age of 44, but at present he is hypothyroid. Both patients are positive for anti-thyroid antibodies and anti-HTLV I virus antibody. Findings of the thyroid biopsy specimens were consistent with Hashimoto's thyroiditis. These data suggest that Hashimoto's thyroiditis develops in HTLV-I carriers who have no clinical evidence of HAM/TSP. PMID- 1286232 TI - Fatal abdominal thorotrast granuloma. AB - We report a case of fatal abdominal thorotrast granuloma seen in a 65-year-old man who had undergone a femoral angiography of thorotrast with some accidental extravasation 49 years previously. As the thorotrast granuloma gradually increased in size, it caused ureteral obstruction, venous thrombosis, and perforation of the urinary bladder and rectum. Symptomatic abdominal thorotrast granuloma is quite rare and this is the first reported case of the granuloma associated with perforation through the urinary bladder and rectum. PMID- 1286233 TI - Essential thrombocythemia developing into refractory anemia and complicated by acute myeloid leukemia. AB - We report a case of essential thrombocythemia (ET) that climaxed in acute myeloid leukemia after developing into refractory anemia. The male patient had ET that was stable for 8 years on carboquone therapy. However, at the age of 72 years he developed an acute terminal illness that was characterized by severe pancytopenia, circulating myeloblasts, extensive bone marrow infiltration by myeloblasts, and an abnormal karyotype [46, XY, t(8q-; 20q+)]. He subsequently died of severe bilateral pneumonia and heart failure. This case suggests that ET may be similar to polycythemia vera; progression to leukemia is unusual except after chemotherapy. Therefore, treatment of patients with asymptomatic ET may not be advisable. PMID- 1286234 TI - Rhabdomyolysis accompanying thyroid crisis: an autopsy case report. AB - Rhabdomyolysis is occasionally associated with metabolic disorders such as diabetic coma, severe electrolyte disturbances and myxedema coma. We describe rhabdomyolysis accompanying thyroid crisis. A 50-year-old man with Graves' disease developed rhabdomyolysis, congestive heart failure and hepatic failure during the course of thyroid crisis and then died of acute renal failure. Postmortem examination revealed rhabdomyolysis in the cardiac and psoas muscles, old myocardial infarction, hepatic centrilobular necrosis, renal cortical necrosis, and follicular hyperplasia in the thyroid. Circulatory collapse and dehydration under excessive hypermetabolic state presumably suppressed the source of energy and oxygen for muscle cells, leading to cellular damage. PMID- 1286235 TI - Paraganglioma associated with hypoglycemia. AB - A 63-year-old female had frequent attacks of palpitations with sweating and occasional loss of consciousness for 7 years before admission. These symptoms and documented hypoglycemia (blood glucose: 46 mg/dl) suggested insulinoma, but computed tomography demonstrated a retroperitoneal tumor which was diagnosed as a paraganglioma by histological examination of the resected specimen. PMID- 1286236 TI - Ocular vitamin therapy. A review and assessment. AB - Vitamin therapy for diseased conditions of the eye has regained momentum in the United States, especially for the treatment of age-related macular degeneration. This review looks at the potential effects of vitamin therapy as it relates to everyday primary eye care practice. The discussion covers the generalities of vitamins, their actions, and potential toxicities. In addition, specific attention is paid to the ocular conditions that have been proposed as benefiting from oral and topical vitamin therapies. The analysis is made on a clinicopathological basis rather than being drawn from anecdotal accounts and unsubstantiated claims. PMID- 1286237 TI - Liability and ophthalmic drug use. AB - Ophthalmic drug use has been an aspect of optometry for more than two decades. Although utilization of these drugs has produced significant changes in the clinical and legal responsibilities of optometrists, the liability posture of the profession has remained unaltered. Studies of malpractice claims against optometrists and ophthalmologists have demonstrated that ophthalmologists are much more likely to be charged with negligence for adverse drug reactions and that drug-related malpractice claims are not a liability issue for optometrists. Based on the experiences of both professions, this paper describes the adverse effects of common ophthalmic drugs, with emphasis on those drug reactions that have resulted in litigation. PMID- 1286238 TI - Chemical treatment of verrucae. AB - Viral warts such as verrucae vulgaris, verrucae plana, and cutaneous horns, when located in close proximity to the eye, can be the cause of chronic, mild conjunctivitis. Removal by chemical cautery using bichloroacetic acid, or by simple excision for pedunculated verrucae, can produce a welcome reduction in symptoms. Chemical cautery may also be employed for the cosmetic treatment of xanthelasma. The proper techniques for cautery and for excision, as well as the evaluation of patients for complications, are discussed. PMID- 1286239 TI - Co-management of patients with glaucoma. PMID- 1286240 TI - A review of common ophthalmic antibacterial and corticosteroid-antibacterial combination drugs. AB - The use of antibacterial agents and corticosteroid-antibacterial combinations are essential to the practice of primary care optometry. In this paper we review common antibacterial drugs available for the treatment of ocular infection or prophylaxis, and offer some clinical guidelines for their use. Corticosteroid antibacterial combination drugs, used primarily to suppress ocular inflammation, are also discussed, and the distinctions between common drugs are described. PMID- 1286241 TI - New antibacterial drugs for topical ophthalmic use. AB - Three new antibacterial drugs have recently been approved for topical ophthalmic use. Ciprofloxacin (Ciloxan) and norfloxacin (Chibroxin) are fluoroquinolones with very broad activity spectra; both have been found to be safe and effective for the treatment of conjunctivitis. Ciprofloxacin, in the commercially available concentration (0.3%), has also been found to be a safe and effective treatment for corneal ulcers. Trimethoprim-polymyxin B (Polytrim) is a new combination product that has been used successfully for the treatment of conjunctivitis. Use of these three new drugs will significantly enhance the ability of the primary care clinician to treat bacterial infections of the cornea and conjunctiva. PMID- 1286243 TI - [Competence sharing between health insurance and medical service]. AB - The borderlines between the areas of competence of the German compulsory health insurance authorities and their Medical Service can be drawn as follows: 1. The German compulsory health insurance body is legally obliged to clarify the facts concerning a patient and his illness. It is therefore imperative for the health insurance body to prepare the ground in each individual case in such a manner that the case in question can be entrusted to a doctor called upon to write an expertise, but the final decision in respect of the insurance coverage rests exclusively with the health insurance body. 2. The Medical Service system is component for helping to find the fact that must be known before the administrative procedure to arrive at a decision is initiated. The expertise given by the Medical Service is a decision help invaluably important on the grounds of specialist knowledge, knowledge of facts and experience gathered from medical practice. Wherever the borderlines of such competencies are overstepped, there is a risk of errors occurring in the expertise and in the administrative decisions based thereon. Such sources of error can be eliminated only if both parties know and accept their limitations and also do not expect the other side to cross these boundaries. PMID- 1286242 TI - Topical carbonic anhydrase inhibitors: a new perspective in glaucoma therapy. AB - Oral carbonic anhydrase inhibitors have been used extensively in the treatment of all types of glaucoma. These agents reduce intraocular pressure by suppressing the rate of aqueous humor formation. Despite their efficacy as ocular hypotensive agents, these agents are not always used for protracted therapy because of significant systemic side effects. Consequently, topically active carbonic anhydrase inhibitors have been a goal of glaucoma researchers for many years. Recently, a new class of carbonic anhydrase inhibitors has entered clinical trials as ocular hypotensive agents. The thienothiopyran-2-sulfonamides, consisting of compounds MK-927, MK-417, and MK-507, are being actively investigated. These agents possess both lipid and aqueous solubility, thereby allowing intraocular penetration through both the cornea and the sclera. They are all potent inhibitors of the human carbonic anhydrase II isoenzyme found in the nonpigmented epithelium of the ciliary body. Preliminary results indicate the order of potency is 2% MK-507 > 1.8% MK-417 > 2% MK-927. Maximum diurnal intraocular pressure reduction generally requires administration of these agents three times daily. Up to a 26.2% reduction in intraocular pressure occurs following multiple-dose therapy with 2% MK-507 given three times a day. These new topical carbonic anhydrase inhibitors appear to be tolerated extremely well; relatively minor ocular side effects, including transient stinging, burning, and tearing, have been frequently reported. In contrast to oral carbonic anhydrase inhibitors, no significant systemic side effects have been documented during clinical testing. Topical carbonic anhydrase inhibitors will probably be marketed in the near future, thus culminating many years of research effort. These agents may provide a safe, effective means of reducing aqueous humor production and intraocular pressure without producing significant systemic side effects. PMID- 1286245 TI - [Health and urban renewal: experiences with the "Healthy Kreuzgassen Quarter- with reference to Vienna--healthy city]. AB - In the context of the WHO-project "Vienna-Healthy City" problems concerning health promotion in an urban renewal district were examined. On that occasion planners and physicians practised intersectoral collaboration. Some of the results, especially the answers of the occupants of two blocks concerning health, environment and health promotion are presented and discussed. PMID- 1286244 TI - [Psychology in the context of medical expert assessment]. AB - One of the tasks of the Medical Service of the compulsory health insurance system in Germany is to conduct follow-up examinations if an employee has been unfit for work for a prolonged period. This involves problems of expertise that are discussed in the present article from the viewpoints of definition, problems and psychological skill in the handling of each individual case. Good interaction between all the parties concerned proves to be an important factor to ensure sociomedical effectivity and to relieve tensions. PMID- 1286246 TI - [Hepatitis A, hepatitis B--incidence of inpatient cases]. AB - The incidence of hepatitis A, treated at hospitals in Austria in the year 1990, was 4,3/10(5) (n = 326), of hepatitis B 3,47/10(5). In hepatitis A the highest incidence was observed in children (5-9 years: 14.3/10(5)). Two peaks were observed in hepatitis B; 20-24 years: 5.93/10(5) and 60-64 years: 3.84/10(5). Both disease had the highest incidence in the district of Vorarlberg (hepatitis A 12.4/10(5), hepatitis B 6.86/10(5)), the lowest in the district of Burgenland (0.37/10(5) and no case of hepatitis B). PMID- 1286247 TI - [Fatality in diabetic coma during foreign travel]. AB - The case history and the autopsy findings of a 44-year-old women who died shortly after her flight to Khartoum (Sudan) in a hospital is presented. The clinical diagnosis in Africa was "shock caused by gastroenteritis". The body was embalmed thoroughly and brought back to Germany. The autopsy was performed just prior to the cremation (according to "section 3 Abs. 2 Nr. 2 Feuerbestattungsgesetz"). Morphological findings (nodular glomerulosclerosis and glycogen nephrosis with Armanni-Ebstein-cells) and postmortem biochemical analyses of vitreous humour led to the diagnosis of a hyperglycaemic coma. The fatal course might have been prevented by sufficient health information to the patient (who suffered from type 1 diabetes); the diagnostic errors in the hospital could have easily been avoided by careful anamnesis and diagnostic procedures. PMID- 1286248 TI - [The federal communicable disease law and refuse disposal from hospitals and medical practices]. AB - Several laws and guidelines on the disposal of waste from hospitals and practice differentiate between diverse types of waste. The LAGA instruction sheet lists five types: type A = hospital waste, type B = medical waste, type C = infectious waste, type D = chemical waste, and type E = human pathological material. Especially the basis of differentiation between medical and infectious waste is the list of notifiable infectious diseases according to section 3 of the Federal Law on Epidemic diseases. Section 10a confines the list to contagious infectious diseases. However, some tropical epidemics and endemic infectious diseases are not taken into account. On the other hand, the list includes a few harmless childhood and other diseases. There is not scientific evidence that wastes of this kind have led to infections in the community. Therefore, the Federal Law on Epidemic Diseases does not seem to be a suitable basis for the differentiation between medical and regulated medical wastes. PMID- 1286249 TI - [Cryptosporidium parvum and Giardia lamblia--incidence in surface and drinking water--significance and detection]. AB - Cryptosporidium parvum and Giardia lamblia are protozoan parasites which can cause gastroenteritis in man and animal. Surface water and drinking-water play an important role in transmission of the disease. The parasites can be detected by extensive and time-consuming procedures only. In this paper we describe a new way to isolate C. parvum and G. lamblia from water by a modification of essential steps of the original method of Rose. The new method applies the separation by flow centrifugation, the purification by different filters and the parasite isolation by percoll density gradient centrifugation. The modified method allows reproducible and by 20% increased recovery rates of cysts. Due to this fast and easy technique this procedure can be integrated in routine examinations. PMID- 1286250 TI - [Data protection and data access (I): federal data protection law and the social welfare code with reference to carrying out occupational medicine epidemiologic studies in Germany]. AB - The regulations applicable to research in occupational epidemiology are the federal data protection (confidentiality) law (BDSG), the social welfare code (SGB), medical professional secrecy regulations and the federal statistics law (BStatG). The SGB, medical professional secrecy, and BStatG codes take precedence over BDSG rulings. This paper discusses BDSG and SGB. Medical professional secrecy and BStatG will be the topic of another publication (Datenschutz and Datenzugang II). The BDSG permits processing and utilization of personal data only if 1. this is permitted by BDSG or a law with higher priority, or 2. if the individual concerned has given her or his informed consent. According to the BDSG private research institutes can have access to personal data collected within non public institutions only via section 28 (2) without consent of the individual. The "research paragraph" section 40 governs the processing and utilisation of personal data by research institutions. As a rule, the SGB permits access to epidemiological data sources only with the informed consent of the individuals concerned. The exception is section 75 SGBX. This paragraph permits disclosure of personal data without the individual's consent by the relevant public institution only if public interest considerably outweighs the private concerns. To our knowledge, however, this clause has had no practical significance. The concept of "informed consent" is discussed in detail, including the requirements for a legal form for informed consent. The legal codes of the BDSG, professional secrecy, and BStatG permit the transfer of personal data if the individuals concerned remain anonymous. This paper deals in detail with the concept of "anonymity".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286251 TI - [Drug-assisted treatment of substance dependence (Drug and Alcohol Symposium, Basel 1992)]. AB - The report on the symposium is an interim account of the treatment of drug addiction in Switzerland. The spread of drugs could not be halted by prohibition. The ideal of a drug-free society does not seem to be translatable into reality. Hence, it is unrealistic to set up continence or sobriety as a goal in the treatment of all addicts, for a proportion of drug dependents or addicts is bypassed or not addressed at all. New approaches based on pharmaceuticals an assisting medication, combined with a diversified allocation of drugs, are under discussion. PMID- 1286252 TI - [Social medicine aspects of persistent somatoform pain disorder]. AB - Persistent somatoform pain disorder is a mental disease the symptom of which- namely, physical pain--cannot be satisfactorily explained by physical findings. This is a frequently occurring disease. But it is often not identified or at least not recognised at an early stage. This leads to negative effects on the patient (e.g. chronification) and on the national social welfare system (for example, costs can mount up to thousands of million DM for medical and social welfare measures). To reduce these problems as far as possible, it is imperative to recognise the disease at an early stage. In particular, those doctors who are mainly engaged in the medical treatment of organs must be familiar with the possibility of functional pain arising from psychic factors, and they must be able to identify it in individual cases, at least as a tentative diagnosis. PMID- 1286253 TI - [Courses in health education as interventions in industry]. AB - Following a brief overview of approaches to workplace health promotion and more specifically of health education courses the paper describes the objectives, contents and methods of a new health course for workers at elevated health risk. This course was developed as part of a comprehensive workplace intervention programme. It comprises three consecutive modules, coping with stress, nutrition, and fitness, each consisting of five 75-minute lessons. Due to intervals of several months between the modules the whole course takes about a year. Course objectives are to improve awareness of own health-related life-style, to mobilise health resources and to develop potentials for health action. Instructional methods include teaching of relevant knowledge, exchange of experience, observational tasks as well as practical exercises. PMID- 1286254 TI - [Secondary data analysis within the scope of occupational medicine epidemiology]. AB - The analysis of large administrative data sets plays an important role in occupational epidemiology in Germany. In this article, examples of such data sets and their use in epidemiologic investigations are presented. The validity of administrative data is discussed. PMID- 1286255 TI - [Basic requirements of documentation in school preadmission examination]. AB - Health screening, health counselling, promotion of pupils and health reporting are the principal marks of school doctor's precautionary health care examinations. The appropriate documentation form must meet the basic requirements of the pupil, of the medical officer and of the evaluation programme. The general concept is realized in three steps: first, definition of the contents, second, operationalisation of the individual items and third, the definition of conventional documenting. PMID- 1286256 TI - [Role of the psychiatrist in the methadone program. Experiences from Frankfurt am Main]. PMID- 1286257 TI - [Legionella and other bacteria in air humidifiers and cooling systems of air conditioning units--a survey]. AB - Air humidifiers using cold water and cooling towers of air-conditioning systems provide the best settings for the growth of bacteria. Hence, we investigated 90 water samples for humidifiers and 15 water samples from cooling towers of hospitals, authorities, schools, and factories. The colony forming units/ml at 20 degrees C and 36 degrees C, the biological activity of added biocidal substances, and the occurrence of legionella were determined. About 90 percent of the samples showed no activity of the biocidal substance added, suggesting the uselessness of such substances. Furthermore, they exercised neither an influence on the CFU of the water samples nor on the occurrence of legionella. Legionella were isolated in 7 per cent of the humidifiers investigated, in 3 per cent of air conditioned buildings, respectively. 13 per cent of the cooling towers contained legionella. The risk of infection by air conditioning systems, humidifiers, cooling towers, and other emitters of infections agents should be controlled by the public health service. PMID- 1286258 TI - [Public health evaluation of pollutants in soil--metals in soil of child playgrounds]. PMID- 1286259 TI - [Toxic adverse effects of oxygen therapy in patients with chronic obstructive bronchitis]. AB - Seventy-eight patients aged 16-78 (48 males and 30 females) in whom COB ran with respiratory insufficiency stage II and III (51 and 27 patients, respectively) and cor pulmonale stage II-A, II-B and III (28, 26 and 8 patients, respectively) received normal-pressure oxygen for 10 min. Posttreatment examinations were performed for pulmonary function, acid and alkaline reactions, oxygen metabolism and blood flow rate. The frequency and intensity of PaCO2 rise in COB patients on oxygen therapy are shown to correlate with severity of restrictive respiratory insufficiency (RRI) and hypoxemia, to relate to reduced capacity of oxygenated hemoglobin for CO2 transport, being independent of the lost hypoxemic stimulus on the respiratory center. Elevated PaCO2 in COB patients on oxygen therapy is not a contraindication to its administration, though dictates its short duration (10-15 min 1-2 times an hour). Complete intolerance to oxygen therapy arose in 5.1% of the COB patients with manifest RRI (VC of due VC being 21.1 +/- 4.13%) and hypoxemia (% HBO2 being 52.6 +/- 8.01%). In effective treatment these patients diminished RRI and restored tolerance to oxygen therapy. PMID- 1286260 TI - [Zinc metabolism in duodenal ulcer]. AB - Zinc concentrations were measured in blood and gastroduodenal mucosa of patients with duodenal ulcer in remission and exacerbation. These were found reduced in plasma but elevated in gastroduodenal mucosa. Healing of the ulcer lesion was associated with positive shifts in zinc metabolism which recovered normal values in ulcer remission. It is concluded that plasma and gastroduodenal levels of zinc reflect the stage of the pathological process in peptic ulcer. PMID- 1286261 TI - [The use of CO2-laser and blood loss during mastectomy]. AB - The problem of radical treatment of breast cancer which largely contributes nowadays to overall cancer incidence in female population is far from being solved. In view of the significance of surgical treatment of breast cancer, the study was initiated to clear up relations between blood loss and kind of surgery. Three groups of patients were assessed for blood loss: subjected to standard mastectomy, modified mastectomy and mastectomy with application of CO2-laser. The blood loss reached 351.2 +/- 11.2 ml, 303.0 +/- 10.8 ml and 155.0 +/- 12.4 ml, respectively. The results evidence the advantage of CO2-laser application in mastectomy in respect to reducing blood loss. PMID- 1286263 TI - [T-cell immunity and immunomodulators in the comprehensive treatment of diffuse toxic goiter]. AB - Age-specific and related to DTG severity lowering of T-lymphocyte count, active and autologous T-lymphocyte number, thymic serum activity were found in 83 DTG patients. These shifts made justified the use of immunomodulator tactivin in 32 DTG patients. The drug was administered in daily subcutaneous doses (1 ml of 0.01% solution) for 5 days. As a result, the T-cell immunity returned to normal values. The highest response occurred in young subjects with moderate hyperthyroidism. Because a single tactivin course failed to bring up a persistent effect, repeat courses are needed to achieve good clinical and immunologic responses. PMID- 1286262 TI - [Specific IgE antibodies in brucellosis]. AB - Specific IgE antibodies and sensitization were assessed in patients with brucellosis in various forms. IgE antibodies were determined with enzyme immunoassay which demonstrated high specificity and sensitivity with conjugate against IgE antibodies in 509 serum samples. Specific IgE antibodies were present in most patients with acute, subacute or chronic brucellosis. Their synthesis seems to be a normal component of humoral immunity in response to brucellosis agent invasion. Allergy in brucellosis seems to arise without participation of the IgE antibodies as there is no correlation between the antibodies levels, the response to Burnet's allergic test and specific leukocytolysis activity. PMID- 1286264 TI - [Current aspects of the problem of chromaffin tumors]. PMID- 1286265 TI - [Isolated thrombosis of the mesenteric branches of the portal vein]. PMID- 1286266 TI - [Outcome of degenerative-dystrophic lesions in the large joints of the lower extremities]. PMID- 1286267 TI - [Acute diseases of the fatty appendages of the appendix]. PMID- 1286268 TI - [New methods for diagnosing pyoinflammatory complications of postoperative wounds]. PMID- 1286269 TI - [Cerebrovascular aspects of antihypertensive therapy]. PMID- 1286270 TI - [Short- and long-term results of the surgical treatment of recurrent goiter]. PMID- 1286271 TI - [Results of Solter's pelvic osteotomy in the treatment of congenital hip dislocation in children]. PMID- 1286272 TI - [Urgent immunocorrection in crush syndrome]. PMID- 1286273 TI - [Elimination of risk factors in prophylactic examinations of hypertensive patients]. PMID- 1286274 TI - [In vivo analysis of the morphofunctional state of myocardial blood supply in ischemic heart disease]. AB - The patency of coronary arteries and morphofunctional features of myocardial microhemocirculation were studied in 40 males with coronary heart disease (CHD) aged 36-59 using intravital coronary angiography, intraoperative left ventricular biopsies assessed electron-microscopically and by semithin sections. In spite of various impairment of the coronary arteries, there was similar clinical presentation. It was found that in addition to atherosclerosis stenosing the main subepicardial vessels in CHD, there appeared a peripheral barrier for the tissue circulation with defective permeability of the myocardial microvessels. Intramyocardial vascular disorders were characterized by noticeable changes in blood rheology, reactivity of resistive vessels and angiosclerosis. The role of multifactor endothelial deformities rose significantly as well as of extravasal compression of the microvessels in interstitial edema and sclerosis, in affected cardiomyocytes. Moreover, the permeability of the histohematic barrier came to be destroyed. The above changes can be considered as reversible, irreversible and amenable to correction. The findings led the investigators to the conclusion on a role of the dysfunction of the intramyo cardial vascular bed as an essential mechanism of CHD pathogenesis responsible for realization of the functional factors. PMID- 1286275 TI - [Occupational traumas in meat processing factories]. PMID- 1286277 TI - [A case of unusual course of erythremia]. PMID- 1286276 TI - [Adenomatous esophageal polyp associated with Barrett's syndrome]. PMID- 1286279 TI - [Pharmacologic approach to the treatment of cancer pain]. PMID- 1286278 TI - [Sarcoidosis and malignant tumors]. PMID- 1286280 TI - [Exogenous drug-induced allergic alveolitis]. PMID- 1286282 TI - A rationale for analytical methodology development. PMID- 1286281 TI - [Forgotten pages of the history of hypnosis in Russia]. PMID- 1286283 TI - Mixed-bed polymeric o-nitrobenzophenone reagents for the on-line derivatization of amines in high performance liquid chromatography. AB - Several polymer-bound o-nitrobenzophenone reagents containing different detector sensitive tags have been combined in the same reactor for the on-line derivatization of amine samples. The formation of multiple derivatives allows numerous opportunities for quantitation from the same injection, and also allows improved identification from the retention times of the multiple derivatives. Changing the reaction conditions changes the ratio of the products formed, so that changes in the ratio of peak heights and areas can also be used for analyte identification. In this work, propylamine was derivatized in acetonitrile on line, precolumn. Changing the reaction conditions, of reaction time, temperature, solvent, presence of catalyst and the components of the reactor, changed the ratio of the derivatives formed. These changes in product formation with changing reaction conditions were applied to the identification and quantitation of amphetamine and methamphetamine in urine. The drugs were identified by the retention times of their derivatives, the ratio of the peak areas of the derivatives and the change in the ratios after changing reaction conditions. Each derivative was also used for quantitation of levels of spiked concentrations of amphetamine and methamphetamine, with relative errors less than 8%. PMID- 1286284 TI - An automated method for the determination of a new potential antiepileptic agent (CGP 33101) in human plasma using high performance liquid chromatography. AB - An automated analytical method utilizing laboratory robotics has been developed and validated for quantifying concentrations of a new antiepileptic drug candidate (CGP 33101) in human plasma. The robotic system aliquots the biological sample, adds the internal standard (CGP 23901) and pH 12 buffer, extracts the compounds from the basified matrix into an organic phase (methyl-t-butyl ether:dichloromethane, 2:1) and concentrates the extracts for reversed-phase, high performance liquid chromatographic (HPLC) analysis. The robotic system is directly interfaced with the HPLC system. Separation is achieved on a Hypersil 3 microns C18 column (4.6 x 50 mm) with ultraviolet detection of the analytes at 230 nm. Specificity was demonstrated by the lack of interfering peaks at the retention times for both the drug and internal standard. Recovery and reproducibility assessments indicated good accuracy (overall mean relative recovery of 102.7%) and precision (coefficient of variation of 4.4 to 7.7%) for CGP 33101 over the concentration range of 50-4000 ng/mL. The limit of quantification (LOQ) is 50 ng/mL. The method has been successfully applied to a clinical study in which normal volunteers received single oral doses of 400-1200 mg of this new drug candidate. PMID- 1286285 TI - A selective HPLC/RIA for dexamethasone and its prodrug dexamethasone-21 sulphobenzoate sodium in biological fluids. AB - A combined high performance liquid chromatography/radioimmunoassay procedure is described for the simultaneous determination of dexamethasone (DEX) and its prodrug dexamethasone-21-sulphobenzoate sodium (DSS) in plasma. After precipitation of the plasma proteins by acetonitrile, the protein-free supernatant was injected onto a C18 reversed phase liquid chromatographic system and DSS- and DEX-containing fractions were collected. Hydrolysis of DSS by 0.01 N NaOH, followed by fractions extraction of both hydrolysed DSS and DEX fractions with ethyl acetate allowed the use of a dexamethasone-specific radioimmunoassay for the selective determination of both compounds. The method is accurate and reproducible (intraday variability for DSS and DEX < 6%, interday variability for DEX 14%), allowing quantification of DEX and DSS as low as 0.3 ng/mL and 0.7 ng/mL, respectively. PMID- 1286287 TI - A high performance liquid chromatographic method for the determination of albuterol enantiomers in human serum using solid phase extraction and chemical derivatization. AB - A high performance liquid chromatographic method was developed for the simultaneous assay of R(-)- and S(+)-albuterol in human serum. The assay involves solid phase extraction as a sample clean-up step and derivatization of racemic albuterol to its diastereomeric thioureas with 2,3,4,6-tetra-O-acetyl-alpha-D glucopyranosyl isothiocyanate. Chromatographic separation was accomplished under isocratic conditions using an octadecylsilane column and a mobile phase consisting of 29:71 acetonitrile:distilled water containing 0.1% triethylamine, pH 4.0 (adjusted with concentrated phosphoric acid) at a flow rate of 0.8 mL/min. The diastereomers were detected using a fluorescence detector set at 223 nm excitation and no emission filter. Racemic bamethane was used as internal standard. Drug to internal standard peak-height ratios were linear over a 2-20 ng/mL range for each enantiomer. The limit of detection of each analyte was 1.0 ng/mL (S/N = 3). PMID- 1286286 TI - Measurement of recombinant interferon levels by high performance immunoaffinity chromatography in body fluids of cancer patients on interferon therapy. AB - The technique of high performance immunoaffinity chromatography was used to measure the levels of recombinant interferon in chronic lymphocytic leukaemia patients enrolled in a phase II recombinant interferon clinical trial. The technique employed a short high pressure chromatography column packed with minute glass beads which had monoclonal antibody, directed against recombinant alpha interferon, immobilized to their surface. This system was used to measure interferon levels in a variety of different human body fluids. A good correlation was found when interferon levels, detected by chromatographic separation, were compared to levels obtained by a conventional radioimmunoassay. PMID- 1286288 TI - Determination of MDL 201,012 at femtomole/millilitre levels in human plasma by liquid chromatography with electrochemical detection. AB - A sensitive and selective liquid chromatographic method to quantitate MDL 201,012 in human plasma was developed and validated. MDL 201,012 (I), diethyl-MDL 201,012 (internal standard, II) and desmethyldiol-MDL 201,012 (masking agent, III) were isolated from basified plasma (2 mL) by solid phase extraction using Bond-Elut C 18 cartridges. Endogenous components were selectively removed prior to eluting the analytes from the sorbent. Components were separated using on-line LC column switching with a cyanopropyl precolumn and a phenyl analytical column. The analytical column effluent was monitored electrochemically at a glassy carbon electrode at a potential of +1025 mV vs. Ag/AgCl. Peak-height ratios were proportional to the amount of MDL 201,012 added to plasma over the range 125-7500 pg/mL MDL 201,012. Absolute recovery of MDL 201,012 from human plasma was > 94% across the calibration range. The minimum quantitation limit was 125 pg/mL. Assay precision (%RSD) ranged from 5.2 to 13% based on the analysis of quality control standards containing 125, 250, 500, 1000, 2500, 5000 and 7500 pg/mL MDL 201,012. Corresponding assay accuracy (% relative error) was +/- 8.5%. The method has been successfully used to quantitate MDL 201,012 in samples from acute dose tolerance studies in human volunteers. PMID- 1286289 TI - Solid phase extraction and simultaneous high performance liquid chromatographic determination of antipyrine and its major metabolites in urine. AB - A reversed phase gradient high performance liquid chromatographic method utilizing solid phase extraction has been described for the simultaneous determination of antipyrine (AP), 4-hydroxyantipyrine (4-OHAP), norantipyrine (NorAP) and 3-hydroxymethylantipyrine (3-OHMAP) in human urine after hydrolysis with beta-glucuronidase. The C-18 sorbent cartridges were conditioned and urine samples were applied, washed with 1 x 4 mL of phosphate buffer and eluted with 3 x 100 microL of 20% v/v of acetonitrile in methylene chloride. The eluent was evaporated to dryness, reconstituted in 100 microL phosphate buffer and injected. The calibration ranges were 2.0-250 micrograms/mL (AP), 2.5-250 micrograms/mL (NorAP), 2.0-250 micrograms/mL (3-OHMAP) and 5.0-500 micrograms/mL (4-OHAP) with regression coefficients of 0.998 or greater. Specificity was indicated by the absence of interferences in chromatogram of blank urine from normal as well as cirrhotic patients. The average recovery was 86.7% for AP, 90.5% for NorAP, 85.2% for 4-OHAP and 74.2% for 3-OHMAP. The within-assay precision as indicated by the reproducibility of the assayed spiked urine was less than 9% in all cases and the between-assay precision was less than 12%. The method was applied to studies on antipyrine metabolism in stable cirrhotic patients. Following administration of a single oral dose of about 1000 mg to nine stable cirrhotic patients and eight age matched healthy volunteers, the cumulative account excreted in the urine up to 48 h for AP and the three metabolites was comparable to other literature reports. PMID- 1286290 TI - Analysis of chlortetracycline by high performance liquid chromatography with postcolumn alkaline-induced fluorescence detection. AB - A high performance liquid chromatographic method for the analysis of chlortetracycline (CTC) using postcolumn fluorescence detection has been developed. After chromatographic separation of CTC on a polystyrene divinylbenzene copolymer column, a highly fluorescent derivative isochlortetracycline (iso-CTC) was formed postcolumn in an on-line reaction coil with the addition of 25% NaOH (w/v). Chromatographic separation was achieved on a PRP-1 column, 15 cm x 4.6 mm, with 27:73 acetonitrile:0.2% perchloric acid (v/v), at 1.0 mL/min. Fluorescence derivatization was achieved by the on-line addition of 25% NaOH (w/v), at a flow rate of 0.2 mL/min, into the column eluant in a post column reaction coil. The reaction coil was 9 m of teflon (1/16 in o.d., 0.3 mm i.d.) knitted into a six-sided coil. The fluorescent derivative was detected at lambda ex 355 nm and lambda em > 389 nm. Using this method after a simple sample cleanup, CTC can be detected in milk at 0.04 micrograms/mL, which is comparable to that obtained by microbiological assays. The detection method was linear between 0.02 micrograms/mL and 4 micrograms/mL. Because of the chromatographic separation, the method is more selective than microbiological assays and more sensitive than ultraviolet detection. With the chromatographic system described, the keto tautomeric forms of CTC and 4-epi-CTC are separated in a system which minimizes their formation on-column. In acidic aqueous organic solutions, the keto tautomer of CTC is the only product formed to any significant amount. PMID- 1286292 TI - Sexuality and HIV/AIDS. PMID- 1286293 TI - Cinderella and the four learning theories. AB - This paper explores the underlying assumptions about teaching, learning and knowledge as it relates to the four learning theories--behaviourist, cognitive, humanist and critical. The assumptions of these four theories are exposed with metaphorical adaptive use of the Cinderella story. It is this author's intention to provoke discussion and arouse interest regarding the four approaches to teaching and learning. PMID- 1286291 TI - Robotic solid phase extraction and high performance liquid chromatographic analysis of ranitidine in serum or plasma. AB - A fully automated assay for the analysis of ranitidine in serum and plasma, with and without an internal standard, was validated. It utilizes robotic solid phase extraction with on-line high performance liquid chromatographic (HPLC) analysis. The ruggedness of the assay was demonstrated over a three-year period. A Zymark Py Technology II robotic system was used for serial processing from initial aspiration of samples from original collection containers, to final direct injection onto the on-line HPLC system. Automated serial processing with on-line analysis provided uniform sample history and increased productivity by freeing the chemist to analyse data and perform other tasks. The solid phase extraction efficiency was 94% throughout the assay range of 10-250 ng/mL. The coefficients of variation for within- and between-day quality control samples ranged from 1 to 6% and 1 to 5%, respectively. Mean accuracy for between-day standards and quality control results ranged from 97 to 102% of the respective theoretical concentrations. PMID- 1286294 TI - Nurses personally and professionally are having to cope with a rapidly changing social, cultural and political environment. PMID- 1286295 TI - Computers and nurses. AB - This paper will consider some of the reasons why nurses must become computer literate and be both aware of, and able to use, information technology. There are advantages for nurses in professional standing, research opportunities and assistance with management problems. Without nursing involvement the use of computers will be imposed on nurses, and it is possible that such an imposition could limit nursing autonomy, exclude nurses from decision making and increase the nurse's workload without benefit. There is a rapid expansion of information and its electronic storage and processing. Are we as nurses aware of the implications of this? Do we really want to know about it? And are we ready to cope with the changes it could make in the way we practice? These are essential questions for curriculum planners now. PMID- 1286296 TI - Saying goodbye: a case study about the experience of hysterectomy. PMID- 1286297 TI - "I honestly thought I was going to die". PMID- 1286298 TI - Community based nurse case managers: a model to meet New Zealand's changing health care needs. AB - Policy-makers are concerned to find ways to improve the quality, accessibility and continuity of care, contain costs and ultimately to reduce the rate of institutionalisation. The health reform in New Zealand proposes to open up the way for nurses to be more extensively and effectively involved in primary and community based care in order to meet these needs. The role of nurses as community based nurse case managers in the United States is reviewed and demonstrates very clearly not only is the quality of health care enhanced but also the client and fiscal outcomes improved. The challenge from the reform is for nurses to see the opportunities and to take the initiative before it is taken by other disciplines. PMID- 1286299 TI - Reintroducing Miss Margaret Macnab. Born: 1900. Interview by Helen Gilmour-Jones. PMID- 1286300 TI - [Internal peritonealization in abdominal hysterectomy. Intermediate analysis of a multicenter study after 126 cases]. PMID- 1286301 TI - [Experiences with 5,648 laparoscopies]. PMID- 1286302 TI - [Selective metastasis surgery of lymph node metastases with gamma probe after marking with tumor-associated radioactive antibodies]. PMID- 1286303 TI - [Significance of primary complete tumor removal for the follow-up of breast cancer]. PMID- 1286304 TI - [Diagnosis of benign and malignant vulvar changes]. PMID- 1286305 TI - [The quality of life of breast cancer patients. Report of a prospective follow-up study]. PMID- 1286306 TI - [Immunohistochemical search for lymph node metastases in females with surgically treated cervix cancer]. PMID- 1286307 TI - [Prognostic significance of tumor markers in cervix cancer]. PMID- 1286309 TI - [p53 protein in patients with Figo stage III cervix cancer]. PMID- 1286308 TI - [Serum tumor markers SCC, TATI and TPS: value in follow-up of females with cervix cancer]. PMID- 1286310 TI - [Screening for endometrial cancer by Mi-Mark cytology and vaginal ultrasound]. PMID- 1286311 TI - [Reduced lymph drainage after pelvic lymph node excision]. PMID- 1286312 TI - [Experiences with primary, papillary serous peritoneal cancer]. PMID- 1286313 TI - [Fallopian tube cancer--an Austrian multicenter study]. PMID- 1286314 TI - [Prolapse of the amputated vaginal canal: correction using fixation to the promontorium]. PMID- 1286315 TI - [Experiences with hysterectomy per surgical pelviscopy]. PMID- 1286316 TI - [Phase contrast microscopy in gynecologic practice]. PMID- 1286317 TI - [Conization non in sano]. PMID- 1286318 TI - [Ligation of the internal iliac artery in hemorrhage after conization]. PMID- 1286319 TI - [Effect of inflammatory stromal reaction on the value of rectal sonography in assessment of parametrial infiltration of cervix cancer]. PMID- 1286320 TI - [Case report of primary irradiated melanoma of the cervix uteri]. PMID- 1286321 TI - [Ovarian metastases of extragenital cancers]. PMID- 1286322 TI - [Treatment of stress incontinence with Burch colposuspension]. PMID- 1286323 TI - [Incontinence operations in patients with hypotonic urethra]. PMID- 1286324 TI - [Urinary tract infections in patients with incontinence problems]. PMID- 1286325 TI - [Treatment of stress incontinence in total prolapse of the uterus]. PMID- 1286326 TI - [Successful use of the erbium-Yag laser in an IVF program]. PMID- 1286327 TI - [Herpes genitalis in Austria. Results of a representative survey]. PMID- 1286328 TI - [1989-1991 indications for Cesarean section in a high risk maternity hospital]. PMID- 1286329 TI - [HELLP syndrome--an indication for Cesarean section]. PMID- 1286330 TI - [Effects of a 60 minute interval increase in oxytocin-induced uterine contraction on the rate of Cesarean sections in comparison with 20 minute interval increases]. PMID- 1286331 TI - [Neopterin (in urine) in patients with pre-eclampsia]. PMID- 1286332 TI - [Rupture of the pregnant uterine horn in uterus bicornis unicollis with survival of mother and child]. PMID- 1286333 TI - [Antithrombin III in pregnancy-induced hypertensive diseases]. PMID- 1286334 TI - [Prenatal therapeutic possibilities in nonimmune hydrops (NIHF)]. PMID- 1286335 TI - [Neuron-specific enolase in newborn infants with and without pathology]. PMID- 1286336 TI - [Surgical-radiological therapy concept in vulvar cancer]. PMID- 1286337 TI - [Prognostic factors in invasive squamous epithelial cancer of the vulva]. PMID- 1286338 TI - [The value of tumor markers in vulvar cancer]. PMID- 1286340 TI - [Cesarean section as a controversy in obstetrics]. PMID- 1286339 TI - [Gmunden--on the medical history of the former royal salt manufacturing city]. PMID- 1286341 TI - [Cesarean section at the Innsbruck University Gynecologic Clinic]. PMID- 1286342 TI - [Obstetrics with low incidence of Cesarean section]. PMID- 1286343 TI - [Breech presentation in primiparous patients: indications for primary Cesarean section?]. PMID- 1286344 TI - [The newborn infant after Cesarean section]. PMID- 1286345 TI - [Quality assurance and Cesarean section. Comments on the WHO recommendations]. PMID- 1286346 TI - [Maternal mortality in Cesarean section]. PMID- 1286347 TI - [Change in indications for Cesarean section]. PMID- 1286348 TI - [The significance of pathologic Doppler findings for Cesarean section indications]. PMID- 1286349 TI - [Psychological aspects of Cesarean section]. PMID- 1286350 TI - [The effect of psychological preparation for delivery on the incidence of Cesarean section]. PMID- 1286351 TI - [Delivery in status post sectio 1976-1991]. PMID- 1286352 TI - [Is palpation of the healed section scar after previous Cesarean section with subsequent vaginal delivery necessary?]. PMID- 1286353 TI - [Cesarean section in premature labor between the 26th and 32d week of pregnancy]. PMID- 1286354 TI - [Vaginal ultrasound in prevention and early detection of cancer]. PMID- 1286355 TI - ["Actually, I should be happy". Post-partum depression]. PMID- 1286356 TI - [Is vaginal delivery at term in pregnant patients with disorders of carbohydrate metabolism a goal?]. PMID- 1286357 TI - [Experiences with pregnancies in HIV-positive females]. PMID- 1286359 TI - [Inhibition of spontaneous uterine contractions by naftidrofuryl]. PMID- 1286358 TI - [Low-dose aspirin in prevention and therapy of hypertension in pregnancy]. PMID- 1286361 TI - [Vaginal ultrasound in diagnosis of interstitial pregnancy]. PMID- 1286360 TI - [Effect of prenatal diagnosis of psychological adjustment of pregnant patients: experiences in management of pregnant patients with fetal abnormalities]. PMID- 1286362 TI - [Doppler blood flow studies in ectopic pregnancy before and after prostaglandin instillation: a follow-up of therapy]. PMID- 1286363 TI - [Physiologic blood flow of the ovary: endosonographic color Doppler blood flow analysis]. PMID- 1286364 TI - Tourette's syndrome and creativity. PMID- 1286365 TI - Hospital twinning in Europe. PMID- 1286366 TI - Can animals teach us medicine? PMID- 1286367 TI - Ghosts, visions, and voices. PMID- 1286368 TI - Geoffrey Rose's big idea. PMID- 1286369 TI - The ups and down of bungee jumping. PMID- 1286370 TI - Sir Austin Bradford Hill and the progress of medical science. PMID- 1286371 TI - Sir Wilfred Grenfell: an athletic missionary. PMID- 1286372 TI - The Amazons within: women in the BMA 100 years ago. PMID- 1286374 TI - Themistocles Gluck: an unrecognised genius. PMID- 1286373 TI - Princess Vera Gedroits: military surgeon, poet, and author. PMID- 1286375 TI - Doctors differ over the German crown prince. PMID- 1286376 TI - Sitting for your portrait. PMID- 1286377 TI - Dickens and doctors: vignettes of Victorian medicine. PMID- 1286378 TI - The ward round. PMID- 1286379 TI - The Physicians' Duel. PMID- 1286380 TI - A surgeon in Yugoslavia in the Second World War. PMID- 1286381 TI - Two nineteenth century surgeons. PMID- 1286382 TI - Learning surgery in Paris. PMID- 1286383 TI - Paintings of a nineteenth century operating theatre. PMID- 1286384 TI - Why Londoners have low death rates from ischaemic heart disease and stroke. AB - OBJECTIVE: To explain the low death rates from cardiovascular disease in London. SETTING: London and the other counties of England and Wales. SUBJECTS: Women living in London during 1901-10 and people in London dying during 1968-78. RESULTS: At the beginning of the twentieth century young women aged 15-34 in London had remarkably low death rates, largely because of low rates for tuberculosis and other infectious diseases and low mortality during childbirth. Their low death rates contrasted with the high rates in girls under 15 years. CONCLUSIONS: Large numbers of young women had migrated into London from agricultural counties in southern England and went into domestic service, where the diet was usually very good. Recent findings suggest that a mother's nutrition and health has a major effect on the risk of cardiovascular disease in the next generation. The low cardiovascular mortality in London is consistent with this, and contrasts with the high mortality from other common diseases. PMID- 1286386 TI - The transformation of maternal mortality. PMID- 1286385 TI - Socioeconomic differentials in mortality: evidence from Glasgow graveyards. PMID- 1286387 TI - Noise and the classical musician. AB - OBJECTIVES: To test the hypothesis that noise exposure may cause hearing loss in classical musicians. DESIGN: Comparison of hearing levels between two risk groups identified during the study by measuring sound levels. SETTING: Symphony orchestra and occupational health department in the west Midlands. MAIN OUTCOME MEASURES: Hearing level as measured by clinical pure tone audiometry. RESULTS: Trumpet and piccolo players received a noise dose of 160% and 124%, respectively, over mean levels during part of the study. Comparison of the hearing levels of 18 woodwind and brass musicians with 18 string musicians matched for age and sex did not show a significant difference in hearing, the mean difference in the hearing levels at the high (2, 4, and 8 KHz) audiometric frequencies being 1.02 dB (95% confidence interval -2.39 to 4.43). CONCLUSIONS: This study showed that there is a potential for occupational hearing loss in classical orchestral musicians. PMID- 1286389 TI - Music making. PMID- 1286388 TI - Mozart's scatological disorder. PMID- 1286391 TI - The practical physics of hearing aids. PMID- 1286390 TI - Medicine--the hearing profession? PMID- 1286392 TI - Does earwax lose its pathogens on your auriscope overnight? AB - OBJECTIVES: To describe the organisms cultured from general practitioners' auriscope earpieces; and to explore general practitioners' perceptions of the possibility of cross infection from contaminated auriscope earpieces and of how their auriscope earpieces are cleaned. DESIGN: Microbiological survey of auriscope earpieces in two general practices and a semistructured questionnaire sent to 105 general practitioners. SETTING: General practitioners served by one district general hospital microbiology laboratory in the north of England. RESULTS: Organisms were cultured from 41 (93%) of 44 auriscope earpieces, of which 14 (32%) carried potential pathogens; four (9%) were heavily contaminated. Of the 85 (81%) general practitioners who responded, 72 (85%) believed that contaminated auriscope earpieces could cause serious infection, 66 (78%) did not clean earpieces between patients, and 70 (82%) thought that patients would mind if they knew that dirty earpieces were used. CONCLUSIONS: Almost a third of auriscope earpieces were contaminated by pathogenic bacteria. Although general practitioners suspected this, most did not ensure that a clean earpiece was used for each patient. PMID- 1286393 TI - Stethoscopes as possible vectors of infection by staphylococci. PMID- 1286394 TI - O little wolves of Leeuwenhoek. PMID- 1286395 TI - Could mannequins menstruate? PMID- 1286396 TI - How to gain weight by looking up. PMID- 1286398 TI - Holy spirit? An unusual cause of pseudomonal infection in a multiply injured patient. PMID- 1286397 TI - An unusual case of neuropathic ulceration. PMID- 1286399 TI - That sinking feeling. PMID- 1286401 TI - A father's worst nightmare. PMID- 1286400 TI - Convulsions at Christmas. PMID- 1286402 TI - To children with love. PMID- 1286403 TI - Medicinal plants: another man's poison. PMID- 1286404 TI - Confessions of a Benedictine drinker. PMID- 1286405 TI - [Academic eulogy of Professor Jean Bobon, titulary member]. PMID- 1286406 TI - [Determination of level of expansion and incidence of rupture of abdominal aortic aneurysms]. AB - We studied 114 patients (out of a cohort of 797 consecutive patients admitted with abdominal aortic aneurysm) who were denied any immediate operation because of patient's refusal, high surgical risk, or small transverse diameter as assessed by CT scanning and ultrasonography. All patients not operated on, underwent from two to six repeated examinations during an average follow-up period of 16.8 months (range, 3 to 132). Forty-seven patients (41.2%) were subsequently operated on electively because of marked increase of transverse diameter of the aneurysm (n = 44) or for other reasons (n = 3), with a death rate of 0%. Eighteen other patients underwent emergency operation for leaking or ruptured aneurysms, and there were five deaths. The incidence of rupture was clearly related to the final diameter value, rising from 0% in aneurysms less than 40 mm to 22% in large size aneurysms (> or = 50 mm). Among the 49 patients not operated on, one died of rupture before operation and five of causes unrelated to the disease. Using individual serial measurements, we determined the linear expansion rate of the aneurysm, which proved to be related to initial diameter values: 5.3 mm/year for diameters less than 40 mm (n = 49), 6.9 mm/year in the 40 to 49 mm group (n = 41), and 7.4 mm/year for diameters of 50 mm or more (n = 24). We also fitted an exponential model to the patient data and determined in each case an "exponential" expansion rate expressed in year-1. The overall mean was equal to 0.129 year-1, and individual values were found to be independent of initial diameter size. The superiority of the exponential model over the linear model was shown to be statistically significant. Our study confirms that expansion of aneurysms is related to initial diameter values and shows that the time evolution of the disease process can be adequately described by an exponential model. It also suggests that rupture of aneurysms is not only related to their size but also to their rate of expansion. PMID- 1286407 TI - [Academic eulogy of Professor Gaston Patriarche, titulary member]. PMID- 1286408 TI - [Trans-laparoscopy surgery, a passing fashion or progress?]. AB - Since the first laparoscopic cholecystectomy performed in 1987 by Philippe Mouret in Lyon (France), there has been a real revolution in the field of visceral surgery: more and more operations are performed by this mini-invasive surgical method: lithiasis of the common bile duct, Nissen and Heller procedure, truncal vagotomies, abdominal and thoracic, supra-selective vagotomies, hernia, appendectomy, band sections during intestinal occlusion, resection of the colon and rectum, oesophagectomies ... In Belgium, more than 3,000 cholecystectomies have been listed in a national registry in which the modalities and complications of this laparoscopic approach have been scrutinized. During the years to come, there will be an important technological development which will make this procedure easier, safer and quicker. Consequences of this new approach cannot completely be foreseen but there are some drawbacks: possible simplification of well established surgical techniques in order to facilitate the laparoscopic approach, causing a deterioration of the long term results, teaching and training difficulties for young and older surgeons, very costly equipment. PMID- 1286409 TI - [Soft tissue ossification: mechanism]. AB - Three experiments: cardiac ligature, subcutaneous implantation of glass diaphragm and regenerated calcaneus tendon transplantation, produce new bone with marrow. The mechanism proceeds in two steps: 1) after trauma or local irritation, mesenchymal fibroblasts enter in division; this young population remains fibrous indefinitely; 2) those young reactive cells, submitted to local oxygen deficiency, build new substances called "stress proteins". Under anoxia, a potent stressor, transplanted new calcaneus tendon ossifies and marrow develops in its core. No immigrant cells participate in this ossicle as it is rejected in a foreign host. Ectopic ossification is an active phenomenon, young fibroblast population building its own inductor, quite different from passive osteogenesis in which inductive message is produced outside the responsive cell. Fracture repair proceeds by an osteogenic reaction from both periosteum and marrow. A third factor is delivered by the cortex: osteogenin or BMP inductor. A fourth osteogenic factor is to be considered: "autoinduction by local stress anoxia". PMID- 1286410 TI - [Academic eulogy of Professor Jean Hamburger, honorary foreign member]. PMID- 1286411 TI - [Protecting man and environment]. PMID- 1286412 TI - [European Organization for Research and Treatment of Cancer (EORTC): objectives, realizations and future perspectives]. AB - The objectives and realizations of the EORTC are described. The activities of the treatment branch are centralized at the EORTC Data Center located in Brussels. Approximately 6000 patients are included every year within clinical trials run by EORTC, involving active participation of more than 2000 physicians distributed in 350 institutions in Europe. 80% of patients included in EORTC trials are located in EC countries. Recently, new cooperative groups have been created in order to study cancers in elderly, tumors related to AIDS as well as invasive fungal infections in cancer patients. New perspectives and further developments include cost evaluations of new therapeutic modalities in oncology as well as quality of life of cancer patients. Furthermore, EORTC promotes the creation of a meta analysis unit. A fellowship program to allow training of medical doctors and statisticians at the EORTC Data Center including scientists coming from Eastern and Central Europe is also encouraging. Every year, EORTC activities lead to at least 40 publications and more than 80 scientific communications allowing rapid diffusion of the results of researches performed. PMID- 1286413 TI - The assessment of carotid and vertebral arteries: a comparison of CFM duplex ultrasound with intravenous digital subtraction angiography. AB - The use of duplex ultrasound with colour flow mapping is compared with that of intravenous digital subtraction angiography (IVDSA) in the investigation of carotid and vertebral artery disease. Ninety-nine carotid and vertebral arteries were examined independently by IVDSA and ultrasound for location and degree of disease in 30 men (mean age 58) and 20 women (mean age 53). For purposes of comparison the carotid tree was divided into six segments. In 46% of cases no disease was detected by either modality. In 36% of cases where disease was found, ultrasound found mild disease in arteries reported as normal by IVDSA. Both modalities detected the six cases of total occlusion found in the study. IVDSA underestimated five cases of major disease found by ultrasound at the bifurcation or in the bulb. Overall agreement in grading vessel segments was good, with 74.5% in complete agreement and 90.3% grading stenoses to within +/- 25% of the other modality. There was good qualitative agreement in the findings for vertebral arteries. In four patients conventional arteriography was also available for comparison. PMID- 1286414 TI - Comparison of a subjective and a quantitative assessment of the neonatal chest radiograph. AB - The aim of this study was to assess if quantitative classification of the chest radiograph appearance at 7 days predicted chronic oxygen dependency (oxygen dependency beyond 8 weeks of age) more accurately than did subjective classification at 28 days of age. Thirty preterm infants, median gestational age 27 weeks, who had chest radiographs taken for clinical purposes at 7 and 28 days of age, were recruited into the study. The 7-day chest radiograph was scored according to the lung volume, presence of opacification, interstitial changes, pulmonary interstitial emphysema and cystic elements. The range of chest radiograph scores was from 0-18, a score of 18 indicating the most abnormal appearance. The 28-day chest radiograph was classified as Type I or Type II chronic lung disease (CLD), according to the presence or absence, respectively, of coarse reticulation. The median chest radiograph score at 7 days of the 30 infants was 5 (range 2-14). In predicting chronic oxygen dependency, a chest radiograph score of 5 at 7 days had 83% sensitivity and 75% specificity, but a diagnosis of Type II CLD at 28 days of age had only 67% sensitivity and 67% specificity. We conclude that a quantitative assessment of the chest radiograph appearance at 7 days is more useful than a subjective assessment at 28 days of age. PMID- 1286415 TI - Myocardial damage following coronary bypass surgery: assessment with antimyosin antibody uptake. AB - To assess the role of 111In antimyosin antibody (AbAm) in the delineation of myocardial damage following coronary bypass surgery, we studied 51 consecutive patients who underwent coronary surgery, 27 of whom had a history of prior myocardial infarction. All patients underwent a diagnostic protocol comprising: (1) 99Tcm pyrophosphate (PYP) and AbAm injection 48 h after surgery (AbAm imaging 24 and 48 h post-injection) (myocardial/background and myocardial/lung ratios were obtained respectively from the computer image); (2) Radioimmunoassay (RIA) serum CK-B levels from samples obtained immediately before surgery, and 24 and 48 h later; (3) clinical and ECG follow-up. Twenty-five patients showed positive AbAm studies, 10 had positive PYP images, and 21 had CK-B levels above normal limits at 24 h. One patient with abnormal AbAm, PYP and CK-B studies had new Q waves on the ECG after surgery. This patient was considered to have sustained a peri-operative myocardial infarction. The large number of positive AbAm studies probably reflects myocardial damage frequently associated with coronary bypass surgery. PMID- 1286416 TI - Computed tomographic appearances of the pelvis following hindquarter amputation. AB - Bilateral and midline symmetry of the normal pelvic anatomy is an aid to the interpretation of computed tomographic (CT) examinations. Following hindquarter amputation (HQA) or partial hemipelvectomy (PHP) the normal anatomical relationships are disturbed. The CT examinations of 15 patients who had undergone either an HQA or a PHP for an advanced musculoskeletal malignancy are reviewed. The new "normal" anatomy revealed displacement of the bladder and small bowel to the side of surgery in one third of patients, more commonly in the PHP cases. There were varying degrees of wasting of the ipsilateral musculature, gluteus maximus muscle flap, erector spinae and psoas muscles, etc., because of partial denervation and disruption of their origin or insertion. Recurrent tumour was identified in eight of 10 cases in which it was clinically suspected prior to the CT examination. Invariably the recurrence arose within the muscle flap at the resection margin. Bone involvement by direct tumour spread was present in three cases. Pitfalls in differentiating recurrent tumour from scar tissue are discussed. PMID- 1286417 TI - Assessment of mammographic film processor performance in a hospital and mobile screening unit. AB - In contrast to the majority of mammographic breast screening programmes, film processing at this centre occurs on site in both hospital and mobile trailer units. Initial (1989) quality control (QC) sensitometric tests revealed a large variation in film processor performance in the mobile unit. The clinical significance of these variations was assessed and acceptance limits for processor performance determined. Abnormal mammograms were used as reference material and copied using high definition 35 mm film over a range of exposure settings. The copies were than matched with QC film density variation from the mobile unit. All films were subsequently ranked for spatial and contrast resolution. Optimal values for processing time of 2 min (equivalent to film transit time 3 min and developer time 46 s) and temperature of 36 degrees C were obtained. The widespread anomaly of reporting film transit time as processing time is highlighted. Use of mammogram copies as a means of measuring the influence of film processor variation is advocated. Careful monitoring of the mobile unit film processor performance has produced stable quality comparable with the hospital based unit. The advantages of on site film processing are outlined. The addition of a sensitometric step wedge to all mammography film stock as a means of assessing image quality is recommended. PMID- 1286419 TI - Does myodil introduced for ventriculography lead to symptomatic lumbar arachnoiditis? AB - Although there is a substantial body of evidence implicating Myodil or Pantopaque as a cause of lumbar arachnoiditis, assessment of the clinically based evidence is complicated by the additional potentially causative factors present in a high proportion of cases. These include pre-existing spinal pathology, traumatic lumbar puncture and surgery. The aim of this retrospective study was to attempt to ascertain whether Myodil introduced via ventricular catheter was associated with subsequent development of symptomatic lumbar arachnoiditis. In 222 patients in whom clinical records were reviewed there was no excess of back pain following ventriculography compared to the general population. Myodil ventriculography does not appear to be a major cause of symptomatic lumbar arachnoiditis. Several unavoidable problems with the methodology of this study are discussed. PMID- 1286418 TI - The influence of needle size on post-myelography headache: a controlled trial. AB - This study aimed to test the hypothesis that the use of fine rather than larger calibre needles for myelography reduces the incidence of post-procedural headache. 160 patients were randomized in a prospective controlled trial of 22 gauge versus 26 gauge needles. The incidence and overall severity of headache as measured at 1, 4 and 21 days after myelography was not significantly different in the two groups. PMID- 1286420 TI - Clearance of iopamidol, a non-ionic contrast medium, by CAPD in patients with end stage renal failure. AB - In normal healthy subjects radiographic contrast media are cleared by the kidneys with a half-life of approximately 2 h and a total body clearance of 8 l/h. The mechanism of contrast clearance has not been previously investigated in chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A study was undertaken to investigate the pharmacokinetics of a non-ionic water soluble radiographic contrast medium (iopamidol) in 10 patients stabilized on CAPD. All patients (eight male, two female) aged 22-68 years (median 53 years) had injection of 30 ml of iopamidol 300 via a forearm vein to investigate subclavian vein patency following previous cannulation for haemodialysis. Venous blood samples, CAPD dialysate and urine were collected for seven days post injection. The mean plasma half-life was 37.9 h (SD 10.6) (range 24.1-57.2 h) for the CAPD patients and was greatly prolonged in comparison to healthy subjects. The total body clearance of iopamidol was also greatly reduced (0.377 l/h). CAPD removed an average of 53.6% of the administered dose (range 36.3-80.8%) whilst an average of 26.9% was excreted in the urine (range 1.3-56.3%). The combined renal and dialysate clearance was up to 93% of the administered dose over the period of the study. There is therefore some evidence for a small extra renal clearance of iopamidol in end-stage renal failure patients. This study has shown for the first time that patients with end-stage renal failure undergoing CAPD have significantly delayed elimination of contrast medium. This should be taken into consideration when extensive or prolonged investigations using contrast medium are proposed. PMID- 1286421 TI - Influence of radiologist grade on fluoroscopic patient dose. AB - The effect of radiologist grade on patient dose during fluoroscopic barium studies was assessed over a one-year period in a large teaching hospital using area-kerma measurements made with a Diamentor M2 system. The number of studies investigated was 164 for barium swallows, 274 for barium meals and 1288 for barium enemas. The patient's AP thickness was assessed at the abdominal level from a formula combining the patient's estimated height and weight. For each study there was no significant change in AP thickness as a function of radiologist grade. For all barium studies there was a trend for both the screening time and the patient dose to fall to a minimum for the grades third year registrar/first-year senior registrar. From this group to consultant level the dose and screening time rose. PMID- 1286422 TI - Comparison of the effect of different reference data on Lunar DPX and Hologic QDR 1000 dual-energy X-ray absorptiometers. AB - We have investigated whether the Lunar DPX (software 3.4) and Hologic QDR-1000 dual-energy X-ray absorptiometers have comparable normal reference databases for the spine and femur of white UK and USA subjects. After conversion for systematic differences in absolute bone density values between the two systems, the reference databases were very similar for the spine in young subjects, but there were clear differences in the femur databases of young females and males of all ages. These differences were confirmed by comparing the percent age-matched and young values determined by the two systems for subjects scanned on both systems. Thus the diagnosis and management of a patient could differ, depending on the system used for the bone density measurements. PMID- 1286423 TI - Sialography using a paediatric intravenous cannula. PMID- 1286424 TI - Primary leiomyosarcoma of the superior vena cava with massive thrombosis treated by local fibrinolysis. PMID- 1286425 TI - Hodgkin's disease--a very late recurrence. PMID- 1286426 TI - Dural venous sinus thrombosis following myelography: demonstration by magnetic resonance imaging. PMID- 1286427 TI - Lethal micromelic facial bones sclerosis dysplasia. PMID- 1286428 TI - Non-endoscopic per oral biliary stent insertion. PMID- 1286429 TI - Yolk sac tumour of the testis in childhood. PMID- 1286431 TI - Acronyms in bone densitometry. PMID- 1286430 TI - Case of the month. Fit and ... well. PMID- 1286432 TI - Latent image fading and mean glandular dose in mobile mammographic screening. PMID- 1286433 TI - La langue et les Levres: cross-language influences on bimodal speech perception. AB - Previous research in speech perception has yielded two sets of findings which are brought together in the present study. First, it has been shown that normal hearing listeners use visible as well as acoustical information when processing speech. Second, it has been shown that there is an effect of specific language experience on speech perception such that adults often have difficulty identifying and discriminating non-native phones. The present investigation was designed to extend and combine these two sets of findings. Two studies were conducted using six consonant-vowel syllables (/ba/, /va/, /alpha a/, /da/, /3a/, and /ga/ five of which occur in French and English, and one (the interdental fricative /alpha a/) which occurs only in English. In Experiment 1, an effect of specific linguistic experience was evident for the auditory identification of the non-native interdental stimulus by French-speakers. In Experiment 2, it was shown that the effect of specific language experience extends to the perception of the visible information in speech. These findings are discussed in terms of their implications for our understanding of cross-language processes in speech perception and for our understanding of the development of bimodal speech perception. PMID- 1286434 TI - Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat. AB - To examine the neurotoxic effects of domoic acid, an amnesic shellfish toxin, electroencephalographic and behavioural experiments were conducted on 38 rats. Injection of domoic acid (0.5-1.0 mg/kg intravenously, or 0.04-0.08 microgram intraventricularly) caused seizure discharges in the hippocampus, tonic-clonic convulsions, and death within a few days. Convulsions and ensuing death were prevented by diazepam. Animals pretreated with diazepam (5 mg/kg, ip) tolerated intraventricular dose of domoic acid 0.4 microgram, but showed a loss of pyramidal neurons mainly in the CA3, CA4, and a part of CA1 areas of the dorsal hippocampus. Learning of a radial maze task was severely impaired in naive rats after intraventricular injection of domoic acid (and diazepam, ip). In the animals previously trained on the maze task, domoic acid interfered with relearning of the same task. These effects appear similar to those of kainic acid and are analogous to the symptoms observed in humans who ingested mussels tainted with domoic acid. PMID- 1286435 TI - Tobacco control: politicking for prevention! PMID- 1286436 TI - Recent developments and current issues in health care in Canada. 1967. PMID- 1286437 TI - The nature and principles of public health. PMID- 1286438 TI - Forty year trends in Canadian tobacco sales. AB - Despite high taxes, the price of tobacco products continues to be a "bargain" for smokers. This paper presents trends since 1950 in real tobacco price index, per capita real disposable income, smoking prevalence, and sales of cigarettes and fine-cut tobaccos. In addition, an "effective tobacco price index", which is the ratio of the real tobacco price index to per capita (age 15+) real disposable income, indexed to a base year (1950) is discussed. This index gives the price of tobacco products as a fraction of real disposable income. The data indicate that, in 1991, the "effective tobacco price" is only 78% of 1950 values. PMID- 1286439 TI - Restrictions on smoking: changes in knowledge, attitudes and predicted behaviour in metropolitan Toronto from 1983 to 1988. AB - To describe recent changes in knowledge, attitudes and behaviour with regard to restrictions on smoking, we compared the findings of population-based surveys conducted in Metropolitan Toronto in 1983 and 1988. In both surveys identical questions and similar data collection procedures were used. There were no changes in knowledge scores regarding the health effects of active smoking or environmental tobacco smoke (ETS), nor in smoking behaviour. In contrast, there were marked changes in attitudes. The population favoured more restrictions on smoking, including prohibition in specific locations, and there was greater support for restrictions on sales and advertising, for differential insurance rates favouring nonsmokers, and for higher taxes on cigarettes. Fewer 1988 respondents reported smoking among their associates and more reported being bothered by others' smoking. The implications for public health education and policy development are discussed. PMID- 1286440 TI - The impact of the decreased prevalence of smoking in Canada. AB - Using data on the prevalence of smoking among different age and gender groups, we estimated the impact of the prevalence of smoking on the present and future mortality of Canadians. In 1989, the life expectancy of male smokers at the age of 45 was 7 years less than non-smokers, among female smokers life expectancy was 4 years less than non-smokers. The total number of smoking-attributable deaths from all causes was estimated for every decade from 1969 to 2019. A decrease in smoking prevalence from 1989 levels to 10% overall in 1999 would result in 15,000 and 6,000 fewer smoking-attributable deaths among women and men, respectively. Continuing the existing pattern of smoking among men and women will result in an increase in the total number of smoking-attributable deaths among women and an increase in the smoking-attributable deaths from lung cancer in both sexes. PMID- 1286441 TI - Survey of smoking prevalence among Canadian nursing students and registered nurses. AB - Patterns of tobacco use are described for members of the Canadian Nurses Association, and students enrolled in the graduating classes of Canadian nursing schools outside Quebec. Seventeen percent of the RNs and 30% of students reported being current smokers. Forty-six of RNs and 10% of students started smoking in nursing school. Although RNs' smoking rates are lower than in any previous survey, students' rates remain high. Smoking prevention and cessation programs are needed in educational institutions. PMID- 1286442 TI - Validation of a survey instrument to measure the extent to which physician and dentist office environments discourage smoking. AB - The health professional's office environment has been identified as one of the potential influences on smoking behaviour of patients. This study compared characteristics of office smoking policies and environments of 30 physicians and 30 dentists using both telephone survey and site visit. The site visit was considered the 'gold standard'. The sequence of interview presentation was randomly reversed for half the physicians and half the dentists to control for order effects. Kappa estimates and two-way Analysis of Variance were used on categorical and continuous variables, respectively. The results show there was a high agreement between the two modes of surveying. Physicians and dentists do not differ in level of agreement and in the consistency of responses obtained by telephone and site visit. We conclude that a telephone survey is a valid method to obtain smoking-related information from health professional offices. PMID- 1286443 TI - Recent trends in lung cancer among Canadians ages 25-44. PMID- 1286444 TI - Smoking and oral health in older adults. AB - This paper examines the relationship between smoking and oral health in older adults. The data are taken from a cross-sectional study of oral health and treatment needs among persons aged 50 years and over living independently in four Ontario communities. Data were obtained from 907 subjects. Half of these reported a history of smoking and one fifth were current smokers. Current smokers were more likely to have lost all their natural teeth than those who had never smoked. Among those retaining one or more natural teeth, current smokers had fewer teeth, fewer functional units, more crown surfaces with decay and more decayed root surfaces. Periodontal indicators showed that the extent and severity of periodontal disease were more marked among current smokers when compared with those who had never smoked. Current smokers also showed a higher prevalence of mucosal disorders and needed more dental treatment. Regression analysis suggested that the links between smoking and oral disorders differ according to the disease in question. PMID- 1286445 TI - A comparison between instructional experience and performance of teachers and nurses delivering a smoking prevention program. AB - This paper focuses on the implementation evaluation strategy of a smoking prevention program and examines differences in instructional experience and implementation of the grade six curriculum in relation to provider type. Arbaseline, nurses (n = 40), compared with teachers (n = 39), reported (a) less previous classroom teaching experience, (b) greater reliance on lecturing and audio/visual materials, (c) less use of small group classroom activities, and (d) less confidence using small group and role playing methods in the classroom. More nurses than teachers believed smoking to be a significant problem in the schools. Nurses had less confidence than teachers in their ability to teach the smoking prevention curriculum. Nonetheless, behavioural observation indicated that nurses implemented the curriculum more completely. However, teachers, at least those who received workshop training, showed some evidence of greater utilization of teaching styles thought to be desirable. PMID- 1286446 TI - Modifiable cardiac risk factors of smoking, elevated serum cholesterol and hypertension: a community survey. AB - This descriptive study assessed the prevalence, perceptions and practices of community residents concerning three risk factors most commonly associated with coronary heart disease: smoking behaviour, hypertension and elevated blood cholesterol/dietary factors. One thousand questionnaires were randomly mailed to residents with a response rate of 48.1%. Results indicated that residents identify smoking and dietary factors as major risks for the development of heart disease. Although the prevalence of hypertension and the frequency of blood pressure screening was similar to other provincial and community surveys that investigated cardiac behaviours, differences were found with the prevalence of smoking behaviour, the frequency of blood cholesterol screening, and knowledge and practices of dietary behaviour. As a result of the study, target groups have been identified and programs have been recommended to meet community needs. PMID- 1286447 TI - Measuring alcohol abuse in the community: consumption, binge-drinking, and alcohol-related consequences ("alcoholism"). AB - This study reported and compared community health indicators for the measurement of alcohol abuse. Using data from the 1989 Hamilton-Wentworth Health Survey, similar rates were found for four differing definitions of alcohol abuse: 1) drinking everyday (5.7%, 95% confidence limit (CL) = 3.8-7.7%), 2) drinking at least 14 drinks in the past seven days (12.1%, 95% CL = 9.2-15.1%), 3) frequent binging on 10 drinks or more (9.4%, 95% CL = 6.9-11.8%), and 4) "alcoholism" as defined by the Michigan Alcoholism Screening Test (MAST) (7.4%, 95% CL = 5.1 9.7%). Binging on five drinks or more occurred frequently (37.0, 95% CL = 32.8 41.1%). All indicators of alcohol abuse from the survey were significantly higher for males as compared to females (p < 0.05), and demonstrated varying distributions by age. Estimates of drinking consumption based on the sale of alcoholic beverages in the community were also examined and found to estimate consumption levels nearly double that of the self-reported survey data. Relevance to public health planning and monitoring is discussed. PMID- 1286448 TI - The experience of an occupational health centre during a prolonged work stoppage. AB - We describe the experience of the occupational health centre at the Sarnia Division of Dow Chemical Canada prior to, during and after a work stoppage of seven months duration. A descriptive analysis was performed of the occupational health case load during the work stoppage compared to the same period one year earlier. Total visits as well as those for dermatologic, upper respiratory, musculoskeletal and those associated with a non-occupationally related situation (e.g., sunburn) exceeded normal frequencies during the first ten weeks of the work stoppage. In particular, there was a peak number of visits during the first two weeks when a 'lock-in' prevented employees from visiting their own physicians except for emergency situations. In the Discussion section, recommendations are outlined to lessen the chance of adverse health effects in workers responsible for operating a chemical plant during a work stoppage. PMID- 1286449 TI - Occupational health nursing in Canada: its social foundation and future. AB - Our purpose in examining the social foundation of occupational health nursing is to better determine the future direction of the profession and its impact on a diverse workforce. Part of what makes up the profession of occupational health nursing is found in its definition: a process that is determined by the interaction between the occupational health nurse, worker, work and workplace; its goal is to assist the worker to achieve his or her optimal level of functioning, primarily through health education, health promotion, prevention of disease and injury and crisis intervention. Much of occupational health nursing is also based on its history and the traditions that have been established. A true understanding, then, of what occupational health nursing's future can be comes from a solid understanding of the history of the profession. As social trends in the past affected the profession, so will they in the future. PMID- 1286450 TI - Intestinal parasite control. PMID- 1286451 TI - Blood lead levels in children. PMID- 1286452 TI - Awkwardness and pimples: health promotion in its adolescence. PMID- 1286453 TI - Outcomes management to create a data base for advanced nursing practice. PMID- 1286454 TI - The clinical nurse specialist as a consultant for play on the pediatric bone marrow transplant unit. AB - A theory of consultation is reviewed and the practical ways in which to implement the consultation role of the pediatric CNS are discussed. A case study is presented to facilitate understanding of the role of the CNS as a consultant in medical play on a pediatric bone marrow transplant unit. PMID- 1286455 TI - Emergence, reinvestment, and renewal. PMID- 1286456 TI - Moving on: recovering from the death of a spouse. AB - Grieving is a complex multidimensional process in response to loss. The grief work involved in coping with a loved one's death does not end when the loved one dies. Rather, the grief work continues through a series of recovery stages. Six stages of recovery--loss, protest, searching, despair, reorganization, and reinvestment--are illustrated and discussed using a case study that highlights a wife's recovery from the death of her husband. Recognition of the stages of grief recovery after a death are significant for health care professionals so that bereavement support may be provided throughout the entire recovery process. PMID- 1286457 TI - A metaphysical journey in a comatose state. AB - This paper is about the intense experience of being in the hospital in a comatose state resulting from an aneurysm with a massive brain hemorrhage and two subsequent surgeries. The event begins with a premonition of what will happen from a street name. The experience of brain surgeries, along with the fine care of the nurses, left me with a truly memorable impression. This paper describes the various feelings and strong emotions that I experienced while in a comatose state. It suggests that a patient in a comatose state can exist in a deep state of emotions close to ecstasy. The paper concludes with gratefulness to all the people who followed me step by step on this journey. PMID- 1286458 TI - "It all began with one little idea". PMID- 1286460 TI - Effectiveness of the CNS as educator and discharge planner. PMID- 1286459 TI - Increasing practice-based research: doctorally prepared clinical nurse specialists may be the answer. AB - The CNS role is proposed as an expert practitioner, educator, consultant, and research within a specialty area. The role, as originally envisioned, was to bridge the gap between practice and research. The research component of the role is frequently given the least emphasis in actual practice. This is problematic for a practice discipline building its scientific base. Many have proposed collaborative practice models to remedy this situation. This paper proposes that a CNS, prepared at the doctoral level, may be the more appropriate solution. Because CNSs maintain a strong practice base, they directly observe problems in the practice setting. With the appropriate research preparation, doctorally prepared CNSs can be in a position to solve clinical problems and advance the science of nursing. PMID- 1286461 TI - Observing the present, envisioning the future. PMID- 1286462 TI - A community health nursing curriculum and Healthy People 2000. AB - The School of Nursing at the University of Alabama at Birmingham recently revised its graduate level community health nursing curriculum based on the priority areas and health objectives in Healthy People 2000. Health priority areas are presented as class topics and provide direction for the students' fieldwork. This paper provides background on the national strategy used to develop the national health objectives, suggestions on how nursing can be at the forefront of influencing the health of the nation, and specifics involved in implementing a community health nursing curriculum using the year 2000 health objectives. PMID- 1286463 TI - Leadership through teamwork. PMID- 1286464 TI - Increasing the impact of the clinical nurse specialist through activity in a shared governance organization. AB - For the CNS frustrated by traditional placement in an organization, participation in a shared governance organization increases opportunities to improve nursing practice and staff satisfaction. CNSs provide nursing expertise and leadership skills for specific committees as they assist staff nurses in meeting committee objectives. The authors also propose the use of a shared governance organization committee structure as a mechanism for CNSs to increase meaningful interaction with staff nurses and influence their professional development. Their model displays four pathways for CNS-staff nurse interaction through shared governance organization activities: examination of the goals of the profession, evaluation of personal needs and goals, assessment of the characteristics of one's work, and transmission of information. The support provided by the CNS in dealing with these issues increases the staff nurses' sense of a "professional self" and, it is postulated, enhances job satisfaction, decision making, and commitment to the organization's goals. PMID- 1286465 TI - Are consultation notes always necessary? PMID- 1286467 TI - Second license for advanced nursing practice? PMID- 1286466 TI - The art of the consultation note. AB - Inherent in the consultation process is the ability to communicate effectively, yet little emphasis is placed on written communication through consultation notes. The art of writing a consultation note is learned primarily through trial and error or by master/apprentice relationships with senior practitioners. This paper reviews the types of consultations in which advanced practitioners are involved and presents a format for preparing a comprehensive consultation note. PMID- 1286468 TI - Value of Holter monitoring in patients with the long QT syndrome. AB - The idiopathic long QT syndrome (LQTS) is an infrequently occurring disorder. It has major clinical impact as patients are prone to syncope, ventricular tachyarrhythmias and sudden arrhythmogenic cardiac death. This paper reports the value of ambulatory electrocardiogram (ECG) monitoring as a diagnostic tool to establish the diagnosis of LQTS. 14 patient with idiopathic LQTS were studied. The results were compared to those of 14 age- and sex-matched healthy control individuals. A 24-hour ambulatory ECG tracing was obtained in each individual. 5/14 patients with LQTS had pathological findings during ambulatory ECG monitoring (2 patients with episodes of torsade de pointes tachycardia, 2 patients with T-wave alternans and 1 patient with bradycardia due to an intermittent SA block), whereas all control persons had normal ambulatory ECG recordings (p < 0.03). Thus, ambulatory ECG recordings may contribute significant diagnostic information in patients with suspected LQTS. PMID- 1286469 TI - Reduced left ventricular diastolic asynchrony after captopril in single vessel coronary artery disease. AB - Impaired left ventricular diastolic function is often found preceding systolic functional abnormality in coronary artery disease. To assess whether captopril improves diastolic function, radionuclide ventriculography was performed before and 1 h after captopril administration in 10 stable effort angina patients with severe isolated stenosis of the left anterior descending coronary artery and in 8 controls. Resting global peak filling rate (PFR) was significantly (p < 0.05) reduced in association with significantly (p < 0.01) increased left ventricular diastolic asynchronous index (delta t) in patients with angina pectoris. Neither global PFR nor regional cardiac function was affected by captopril, although delta t was significantly (p < 0.05) reduced from 70 +/- 18 (SD) to 51 +/- 25 ms in patients with angina pectoris. A significant (p < 0.01) correlation was observed between percentage changes in peak ejection rate and in PFR in all subjects. Thus, captopril improves left ventricular asynchrony in patients with stable angina, although global diastolic function affected by systolic function remains unchanged. PMID- 1286470 TI - Ibopamine as a valuable adjunct and substitute for dopamine in bridging therapy before heart transplantation. AB - Ibopamine is an active dopamine analogue leading to improved renal perfusion and afterload reduction in heart failure. This report describes casuistic experiences in patients with severe heart failure awaiting heart transplantation. All patients could be stabilized, intravenous catecholamines be discontinued, and diuretics be reduced. Six of seven patients could be successfully transplanted. No major side effects were noted. Thus ibopamine can be a suitable adjunct for patients with endstage heart failure. PMID- 1286472 TI - Characteristics and prognosis of patients with acute myocardial infarction in relation to whether they were treated in the coronary care unit or in another ward. AB - The characteristics and the prognosis in 921 consecutive patients with acute myocardial infarction (AMI) admitted to one single hospital are described and related to whether they were treated in the coronary care unit or not. Patients treated in the coronary care unit (n = 779) had a 1-year mortality rate of 26% as compared with 41% for patients treated in general wards (n = 115; p < 0.001) and 74% for patients treated in the intensive care unit (n = 27; p < 0.001). Patients treated outside the coronary care unit had a different risk factor pattern including a higher age and a higher prevalence of a previous cardiovascular disease. Independent clinical risk indicators for death among patients in the coronary care unit were in order of significance, high age (p < 0.001), arrhythmia on admission (p < 0.01), acute congestive heart failure on admission (p < 0.01) and a history of diabetes mellitus (p < 0.05). In patients treated in general wards, the only risk indicator for death was a history of congestive heart failure. PMID- 1286471 TI - Placebo treatment in congestive heart failure. AB - In order to evaluate the effect of placebo treatment in congestive heart failure, we retrospectively studied 24 patients with moderately severe congestive heart failure who participated in heart failure treatment trials performed over the past 10 years in the Ohio State University Heart Failure Research Laboratory. Placebo-treated patients from 4 placebo-controlled trials comprised the placebo treatment group (n = 15), while one natural course-controlled trial provided patients for the non-placebo control group (n = 9). Changes in symptoms, left ventricular function and exercise duration were assessed following an 8-week course of therapy. Chronic placebo therapy resulted in an 81-second improvement in exercise duration which was statistically significant when compared to pretreatment baseline and to the duration achieved by the nonplacebo control group. Clinically, functional class improved significantly by 27% above baseline only for the placebo treatment group. Indices of left ventricular function did not change for either group. The salient feature of this study is that the placebo treatment effect, while believed to exist in congestive heart failure, has never been demonstrated in a manner which controlled for the natural course and variability of the disease process. The operative components of the placebo effect remain unknown, and further investigation will be necessary to elucidate the underlying mechanisms involved. However, the importance of this phenomenon lies not only with the response to and effects of placebo therapy but also in the role that the placebo effect plays in what is generally presumed to be the predominant responses, effects and benefits of active drug therapy. PMID- 1286474 TI - Kinetics of technetium-99m-Sestamibi and thallium-201 in a transient ischemic myocardium animal model: insight into the 'redistribution' phenomenon. AB - This study was designed to determine the redistribution potential for technetium 99m (99mTc)-hexakis-2-methoxy isobutyl isonitrile (99mTc-Sestamibi) as compared to thallium-201 (201Tl) in a transiently ischemic swine heart model. The left anterior descending coronary artery (LAD) was totally occluded for 10 min. One minute prior to the release of the LAD, 99mTc-Sestamibi, 201Tl and a set of 95Nb radiolabeled microspheres (15 microns) were injected. A second set of 51Cr radiolabeled microspheres was injected prior to sacrifice in order to document reflow. Animals were sacrificed at different times post-LAD release (ranging from 1 min to 4 h). The left ventricle was sectioned into 0.2- to 0.5-gram pieces for the gamma spectroscopic counting of the 99mTc-Sestamibi, 201Tl and radiolabeled microspheres. Linear regression analysis of radiotracer localization versus microsphere-determined regional myocardial blood flow (rMBF) demonstrates an initial slight filling in of 99mTc-Sestamibi into transiently ischemic zones, with subsequent stable kinetics up to 4 h (i.e., it does not further redistribute). In comparison, the ischemic to normal ratios for 201Tl activity increase progressively in a time-dependent manner. These differences between 99mTc-Sestamibi and 201Tl might be explained on the basis of their blood clearance kinetics and/or their net clearance from normal and ischemic zones of the heart. It is concluded that 99mTc-Sestamibi is a stable and reliable indicator for rMBF over time, and that the lack of normalization of 99mTc Sestamibi into transient ischemic zones will necessitate two separate injections for differentiation between ischemia and persistent defects. PMID- 1286473 TI - Continuous vectorcardiography in patients with chest pain indicative of acute ischemic heart disease. AB - To assess the clinical usefulness of continuous on-line vectorcardiography (VCG), we studied 61 patients admitted to the coronary care unit (CCU) with chest pain, supposedly ischemic. Continuous VCG was performed for 24 h, monitoring QRS vector difference (QRS-VD), ST-change vector magnitude (STC-VM) and ST vector magnitude (ST-VM) measured 20 and 60 ms after the termination of the QRS complex. The patients were divided into four groups based on the final diagnosis; group A, 15 patients with normal exercise tests and extracardiac causes of chest pain; group B, 15 patients with unstable angina; group C, 15 patients with non-Q-wave myocardial infarction (MI); group D, 16 patients with Q-wave MI. Treatment was given according to a normal routine. Of 31 patients with MI, 16 received treatment with streptokinase. Groups A and B showed no significant permanent changes in QRS-VD, STC-VM or ST-VM. However, group B showed a higher occurrence of transient episodes (duration: 2 min-6 h) of a significant change of QRS-VD by > 15 microVs and of STC-VM, ST-VM 20 and ST-VM 60 by > 0.1 mV. Groups C and D showed both permanent changes and transient episodes for the studied vector parameters. Transient episodes were significantly fewer in group D than in group B. In patients with MI, the permanent change of vector parameters evolved more rapidly and reached a plateau earlier in those treated with streptokinase (QRS VD: 178 +/- 82 vs. 293 +/- 100 min, p < 0.001; ST-VM 20: 142 +/- 75 vs. 293 +/- 89 min, p < 0.005). The magnitude of the end value for QRS-VD correlated with infarct size estimated by the maximal value of creatine kinase (r = 0.89; p < 0.001). We conclude that in patients admitted to the CCU with chest pain, continuous VCG monitoring early differentiates patients suffering from ischemic heart disease (IHD) from patients without IHD. It also differentiates patients with unstable angina from patients with MI. PMID- 1286475 TI - The value of chest pain during the exercise tolerance test in predicting coronary artery disease. AB - The predictive power of 10 common exercise test parameters compared with coronary angiography was studied. Only the exercise electrocardiogram (EXECG), maximal rate pressure product (MAXRPP), and exercise chest pain (EXCP) contributed unique predictive information with the emergence of two interactions involving EXCP (EXCP.EXECG and EXCP.MAXRPP). IN CONCLUSION: (1) EXCP appears to be a more serious finding only in those higher risk individuals with either a positive EXECG or lower MAXRPP; (2) EXCP and its interactions may help discriminate between anginal and nonanginal, exertional chest pain, and (3) the contradictory results found when EXCP was allowed to interact may explain conflicting results in previous multivariate models regarding the predictive significance of EXCP. PMID- 1286476 TI - Influence of ocular tropicamide on exercise testing. AB - This study was aimed to evaluate the effects of tropicamide 0.5% eye drops on cardiovascular parameters during exercise testing. The study group included 154 healthy subjects (mean age: 44.7 +/- 8 years). The subjects were divided into three groups according to the size of the pupils at the onset of exercise: A: pupils not dilated (n = 27), B: pupils partially dilated (n = 90) and C: pupils widely dilated (n = 37). They were compared to 66 healthy controls (age 43.8 +/- 8) who did not receive the drops. Rest and exercise parameters were affected in groups A and B, while the results of group C resembled those of the controls: (a) resting heart rate -66.7, 66.6, 70.9 and 69.3, respectively (p = 0.03); (b) heart rate at 50 and 100 W - 104, 107, 110 and 111 (p = 0.01) and 131, 131, 137, 139, respectively (p = 0.01); and (c) peak systolic blood pressure - 192, 186, 183, 175; respectively (p = 0.004). Reanalyzing the data by scoring of visual impairment gave identical results. As a whole, the study group achieved higher work loads than the controls (126 vs. 119 W; p = 0.03). We conclude that the instillation of ocular tropicamide has definite effects on cardiovascular parameters, both at rest and during exercise. Mainly, patients showed a lower heart rate at the initial levels of exercise. However, at symptom-limited level, tropicamide does not influence a patient's ability to achieve the target heart rate, and stress testing results are not altered by the drug. PMID- 1286477 TI - Right atrial myxoma presenting with recurrent episodes of pulmonary embolism. AB - We observed a right atrial myxoma presenting with recurrent episodes of pulmonary embolism, the diagnosis of which was made approximately 2 years after the initial symptoms appeared. We emphasize the importance of prompt recognition and subsequent surgical treatment of cardiac myxoma because embolism by tumor fragments is a potentially fatal complication of this condition. PMID- 1286478 TI - Percutaneous balloon mitral valvotomy in pregnancy using the Inoue balloon catheter. AB - Percutaneous balloon mitral valvotomy (PBMV) using the Inoue balloon catheter was performed successfully in 2 patients with severe mitral stenosis refractory to medical treatment during pregnancy. Because of its unique design and ease of manipulation, we recommend the Inoue balloon catheter for performing PBMV in selected patients with mitral stenosis during pregnancy, as procedure and fluoroscopy times can be significantly shortened. PMID- 1286479 TI - Antiphospholipid antibodies in mitral valve prolapse. PMID- 1286480 TI - Morbidity from congestive and hypertrophic cardiomyopathy in the Minneapolis-St. Paul metropolitan area: 1979-1984. PMID- 1286481 TI - Effect of smoking on the oxidative processes of cardiomyocytes. AB - The effect of prolonged (14 days) passive smoking on the respiration of isolated cardiomyocytes in rabbits using various substrates (pyruvate, glutamate, succinate) was studied. The endogenous respiration of cardiomyocytes was not affected whereas stimulated respiration as well as the ratio of stimulated to endogenous respiration significantly decreased. These results complement previous studies in which the effect of smoking on the metabolic processes of heart muscle mitochondria was measured. In conclusion, prolonged smoking may provoke myocardial dysfunction and in this way may contribute to the development of heart failure in chronic smokers. PMID- 1286482 TI - Effect of pacing on epinephrine-stimulated atrial natriuretic factor release. AB - Previous in vitro studies showed that epinephrine stimulation can induce atrial natriuretic factor (ANF) release only form the right atrium but not from the left. In addition, sinus node has been shown to play an important role in the release of ANF. In vitro studies were done in isolated left and right rat atria to determine if pacing can induce the left atria to release ANF during epinephrine stimulation. ANF concentrations in the perfusate were measured by a radioimmunoassay method. Epinephrine increased ANF release in the right atria (from 6.3 +/- 0.8 to 10.8 +/- 0.9 pg/min/mg), but not in the unpaced left atria (4.2 +/- 0.4 and 4.2 +/- 0.3 pg/min/mg). However, when the atria were paced, ANF release rose in both the left (from 6.2 +/- 0.5 to 11.5 +/- 1.4 pg/min/mg) and right (from 8.4 +/- 1.15 to 16.6 +/- 1.8 pg/min/mg) atria with epinephrine addition. These results suggest that atrial contraction and tension play an important role in epinephrine-stimulated ANF release. PMID- 1286483 TI - Effects of cloricromene on ischemia-reperfusion myocardial damage in the rabbit. AB - Cloricromene, a compound with several biological activities which suggest a therapeutic role in thrombosis or ischemic disease, has been studied for its effects on the extension of myocardial damage and the production of oxygen free radicals during periods of ischemia and reperfusion. In twenty rabbits the left anterior descending coronary artery (LAD) was occluded and cloricromene (3.6 micrograms/kg/min; n = 10) or placebo (n = 10) were continuously infused. After 50 min the artery was reopened and after 20 min of reperfusion a biopsy was obtained from the anterior wall of the heart in the LAD area and from the posterior wall (control myocardium) prior to sacrifice. Both samples were used for chemiluminescence measurement (free-radical production) and ultrastructural studies. In the placebo group all rabbits showed ST-segment changes during ischemia and reperfusion arrhythmias, while in the cloricromene group there were transient ST elevations in 4 animals which reverted at higher infusion rates of the drug. The chemiluminescence values were 18,017 +/- 1,956 and 8,583 +/- 918 cpm/mg protein (p < 0.001) in the anterior and posterior walls of the left ventricle, respectively, for the placebo group, and 7,767 +/- 992 and 8,333 +/- 832 cpm/mg protein (NS), respectively, for the cloricromene group. The ratio between the anterior and posterior wall was 2.27 +/- 0.37 for the placebo group versus 0.95 +/- 0.11 for the cloricromene group (p < 0.001). In ultrastructural studies, the anterior wall in the placebo group showed irreversible myocyte injury and infarction as well as mitochondrial damage. Samples from the cloricromene-treated group showed, in general, preservation of myocyte architecture or minor signs of injury. These results illustrate clearly the protective effect of cloricromene during damage induced by ischemia and reperfusion in the rabbit. PMID- 1286484 TI - Endometriosis: recurrence and retreatment. AB - Endometriosis, a condition in which endometrial tissue sheds and becomes attached to extrauterine sites, appears to be a progressive or recurrent disease. Although there are a variety of treatment options, the only cure for endometriosis is total abdominal hysterectomy with bilateral oophorectomy. For women who wish to preserve fertility, however, this is not a desirable choice. Because the symptoms of endometriosis suggest a hormonal relationship, pharmacologic management entails inducing anovulation. A concern of both physicians and patients is recurrence of endometriosis after initial response to therapy. Whether symptoms represent recurrent disease or progression of preexisting implants is still unknown. A repeat course of therapy with danazol, a synthetic androgen, may be tried for retreatment of endometriosis. Another option is the progestins. Conservative surgery (ie, laparoscopy) is also an option, but often must be repeated for pain control; combination pharmacologic/surgical therapy, although in widespread use, is not without disadvantages and requires further investigation. PMID- 1286485 TI - The effects of immune globulin on endotoxemia. AB - Ten patients (mean age, 40 years; 2 women) with endotoxemia received 2.5 gm of immune globulin daily for 4 days or 5 gm daily for 2 days. In all patients, plasma endotoxin levels decreased to normal levels (< or = 9.8 pg/ml) within a mean of 3.2 days after starting immune globulin treatment, and body temperatures decreased to < 37 degrees C within 4.5 days. In 10 antibiotic-treated (control) patients with endotoxemia who did not receive immune globulin, plasma endotoxin levels declined to normal levels in 6 and their body temperatures dropped to normal levels within 5.0 days; no changes in body temperature were noted in the 4 patients whose plasma endotoxin levels did not decrease. PMID- 1286486 TI - Comparison of etodolac and diclofenac in osteoarthritis of the knee. AB - This study compared the efficacy and safety of etodolac, a new nonsteroidal anti inflammatory drug of the pyranocarboxylic class, with that of diclofenac in patients with osteoarthritis of the knee. A total of 172 patients entered this double-blind, parallel study and were randomly assigned to receive etodolac 600 mg/day (n = 85) or diclofenac 150 mg/day (n = 87) for 8 weeks. Both treatment groups showed a statistically significant reduction in pain at the second week and significant improvement (P < or = 0.05) from baseline in all efficacy assessments for the remainder of the study. Seventeen (20%) patients in the etodolac group and 21 (24%) patients in the diclofenac group reported at least one adverse event. Seven (8%) patients treated with etodolac and eight (9%) of those receiving diclofenac withdrew prematurely from the trial. One diclofenac treated patient had a significant increase in alanine aminotransferase at the final evaluation. The results of this study indicate that etodolac was well tolerated and as effective as diclofenac in relieving the signs and symptoms of osteoarthritis. PMID- 1286487 TI - Glyburide versus glipizide in the treatment of patients with non-insulin dependent diabetes mellitus. AB - Thirty-four adults with non-insulin-dependent diabetes mellitus were randomly assigned to receive either oral glyburide or oral glipizide in a multicenter comparative trial. Fasting blood glucose and hemoglobin A1c (HbA1c) were assessed at the beginning of the titration phase, the beginning of maintenance therapy, and the end of maintenance therapy. Maintenance therapy lasted approximately 3 months. The initial mean total dose of glyburide (5.4 mg) was significantly lower than that of glipizide (10.6 mg) (P = 0.04) and remained significantly lower at the beginning of maintenance therapy (7.8 mg versus 15.3 mg; P < 0.01) and at the end of the trial (10 mg versus 16.8 mg; P = 0.05). Although significant differences were not detected for fasting blood glucose or HbA1c, patients received higher total doses of glipizide compared with glyburide at the middle and final evaluations to maintain the fasting blood glucose between 3.9 and 10 mmol/L and HbA1c at < 9%. No serious adverse reactions were observed in any patient. These results indicate that doses of glipizide required to maintain blood glucose between 3.9 and 10 mmol/L and HbA1c at < 9% increased over time. Seventy-five percent of patients receiving glyburide were controlled with once daily dosing compared with 29.4% of those treated with glipizide. Both glyburide and glipizide provide safe and effective treatment for patients with non-insulin dependent diabetes mellitus, but more patients will benefit from once-daily therapy with glyburide. PMID- 1286488 TI - Effects of manidipine and delapril on serum lipids, lipoproteins, and apolipoproteins in patients with mild to moderate essential hypertension: a randomized trial with one-year follow-up. AB - Forty-five patients with mild to moderate essential hypertension were randomly assigned to receive 10 to 40 mg of manidipine HCl or 15 to 60 mg of delapril daily for 12 months. In the manidipine-treated group were 13 women and 5 men (mean age, 48.2 years) and in the delapril-treated group 11 women and 11 men (mean age, 53.7 years). Blood samples were taken at baseline and after 6 and 12 months of treatment and again at 2 months after treatment discontinuation. Significant reductions in blood pressure were observed in both treatment groups. The reduction in diastolic blood pressure was significantly greater in the manidipine-treated patients than in the delapril-treated patients; no significant between-groups differences in systolic blood pressure were noted. Heart rate increased significantly in the manidipine group. No changes in serum levels of total cholesterol, triglycerides, and high-density and low-density lipoprotein cholesterol were noted during or after treatment. In the manidipine group, a small but significant decrease in apolipoprotein (apo) A-I and an increase in lipoprotein(a) were found at 6 months and a significant increase in apo A-II and apo E at 12 months; in the delapril group a significant decrease in apo A-I was found at 6 months. The results indicate that both manidipine and delapril are lipid-neutral antihypertensive drugs, since neither drug greatly affected serum lipid metabolism. PMID- 1286489 TI - Effects of temperature, solution composition, and type of container on the stability and absorption of carmustine. AB - The stability and absorption of carmustine were studied comparatively in glass flasks and Stedim 6 bags. Stedim 6 is a new, multilayer, polyethylene-lined film. When stored at room temperature (22 degrees C +/- 2 degrees C) in the dark, carmustine decomposed in 5% dextrose solution and more so in 0.9% sodium chloride solution. When stored at 4 degrees C +/- 0.5 degrees C, the losses were identical in the glass flasks and Stedim 6 bags (about 11% after 72 hours). As long as they are kept in the dark at 4 degrees C, carmustine admixtures can be prepared up to 48 hours before administration, in either dextrose or sodium chloride isotonic solutions, and stored in either glass flasks or Stedim 6 bags. PMID- 1286490 TI - Enoxacin in the treatment of typhoid fever. AB - Enoxacin 400 mg twice daily was given orally to 40 patients who had Salmonella typhi- or Salmonella paratyphi-positive blood or bone marrow cultures. One patient was switched to parenteral therapy within 48 hours of study enrollment, but the remaining 39 patients were given enoxacin for 10 to 14 days. All 39 patients were cured by enoxacin, even though 23 (58.9%) strains were resistant to cotrimoxazole and 16 (41%) strains were multiply resistant to ampicillin, chloramphenicol, and cotrimoxazole. No adverse events necessitated the interruption of therapy. In this study, enoxacin was well tolerated and efficacious in the treatment of typhoid fever. PMID- 1286491 TI - Hypercoagulable state in patients with hypercholesterolemia: effects of pravastatin. AB - Molecular markers of the coagulation system and the effects of pravastatin on lipid levels and the coagulation markers were studied in 48 patients (mean age, 55 years) with hypercholesterolemia (plasma total cholesterol levels > 280 mg/dl). Each patient received 10 mg of pravastatin daily for 3 months. Plasma total cholesterol and low-density lipoprotein cholesterol levels decreased significantly during treatment and high-density lipoprotein cholesterol levels increased significantly. Above-normal plasma levels of thrombin-antithrombin III complex, fibrinopeptide A, FDP-D-dimer, plasminogen activator inhibitor-I, and thrombomodulin were found in the patients before treatment; each of these was reduced significantly during treatment. The findings suggest the presence of a hypercoagulable state in hypercholesterolemia and that pravastatin might prevent the hypercoagulable state by reducing hypercholesterolemia. PMID- 1286493 TI - Milestones in clinical pharmacology. Opium and its derivatives. PMID- 1286492 TI - Enalapril and verapamil in the treatment of isolated systolic hypertension in the elderly. AB - A prospective, investigator-blinded, randomized study was conducted to compare the efficacy and tolerability of enalapril and verapamil in the treatment of isolated systolic hypertension in elderly patients. Of the 115 patients who completed the study, 58 received enalapril and 57 verapamil. The goal of treatment was a systolic blood pressure < 160 mmHg and a reduction of at least 20 mmHg below baseline. The initial daily dose of enalapril was 5 mg, and of verapamil 240 mg. The dosage was titrated upward until the goal blood pressure was achieved. At the end of the titration period, systolic and diastolic blood pressures were significantly decreased (P < 0.001) in both patient groups. Blood pressure remained significantly decreased (P < 0.001) in both groups during the 8 week maintenance treatment period. There were no significant differences between groups. Two patients in the enalapril group and nine patients in the verapamil group were withdrawn from the study because of adverse effects. The results of this study demonstrate that enalapril and verapamil are well tolerated and effective in the treatment of isolated systolic hypertension in the elderly. PMID- 1286494 TI - Assessing health-related quality of life: application to drug therapy. AB - There is growing awareness among the principal stakeholders in health care that health outcomes data should be used in the evaluation of medical care interventions. Health-related quality of life is a patient-reported health outcome that is gaining increasing attention. In fact, in certain diseases, quality of life may be the most important health outcome to consider in assessing treatment efficacy. Quality of life is a construct commonly viewed as having several dimensions or domains. Although the terminology may differ depending on the author, the basic dimensions of health-related quality of life are physical status and functioning, emotional/psychological status, social functioning, and disease- or treatment-related symptomatology. There are a number of methodologic issues in the measurement of quality of life that must be carefully considered when designing a study or evaluating existing research. These issues include general or disease-specific measures, index or profile outcome measures, dimensions measured, relative importance of dimensions, reliability of the measure, and validity of the measure. This paper provides a brief overview of health-related quality of life and its measurement in the context of drug therapy. PMID- 1286495 TI - Reversal of central nervous system effects by flumazenil after intravenous conscious sedation with midazolam: report of a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group I. AB - Flumazenil, a benzodiazepine antagonist, reverses the residual central nervous system effects of benzodiazepines. In this US double-blind, multicenter study, the efficacy of flumazenil was compared with that of placebo in antagonizing the effects of midazolam, a benzodiazepine used to induce intravenous conscious sedation. The mean dose of flumazenil was 0.7 mg, administered intravenously. At 5 minutes posttreatment, 82% of 131 flumazenil-treated patients, compared with 15% of 65 placebo-treated patients, demonstrated complete reversal of sedation. In 85% of patients who responded to flumazenil, this reversal of sedation was maintained throughout the 180-minute observation period. Psychomotor performance returned to prestudy levels 5 minutes posttreatment in 87% of the flumazenil treated patients, compared with 28% of the placebo-treated patients. At the doses administered, flumazenil was less effective in reversing midazolam-induced amnesia, with only 60% of patients demonstrating partial recovery of memory. It was, nevertheless, more effective than placebo. Flumazenil was well tolerated. Dizziness (10%) and nausea (9%) were the most frequently reported adverse effects. Results of this study demonstrate that flumazenil antagonizes the central nervous system effects of midazolam after intravenous conscious sedation. PMID- 1286496 TI - Reversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids: a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II. AB - The efficacy and safety of flumazenil in antagonizing the central effects of the benzodiazepine midazolam was demonstrated in patients in whom conscious sedation was induced with midazolam plus an opioid (fentanyl, meperidine, or morphine). In a double-blind, multicenter study, 240 patients were administered flumazenil postoperatively at an average intravenous dose of 0.7 mg (7 ml) and 114 patients were administered an average dose of 9 ml placebo. Complete reversal of sedation was observed in 80% of flumazenil-treated patients and 30% of placebo-treated patients 5 minutes posttreatment. In 87% of patients who responded to flumazenil, the level of alertness was maintained throughout the 180-minute observation period. Midazolam-impaired psychomotor performance returned to normal 5 minutes posttreatment in 80% of the flumazenil-treated patients and 28% of the placebo treated patients. Flumazenil was less effective in reversing midazolam-induced amnesia, with only 70% of flumazenil-treated patients (and 15% of placebo-treated patients) able to recall the picture shown them at the 5-minute assessment, and fewer patients able to recall pictures shown at later times. Flumazenil was well tolerated, although adverse effects were reported slightly more often than in the placebo group. The most frequent adverse events in both groups were dizziness and nausea. Vital signs were not affected. PMID- 1286497 TI - Reversal of central benzodiazepine effects by flumazenil after conscious sedation produced by intravenous diazepam. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group I. AB - Flumazenil is a competitive benzodiazepine antagonist that rapidly reverses the residual effects of benzodiazepines following intravenous conscious sedation. In a double-blind, multicenter study, postoperative patients who had been sedated with intravenous diazepam were randomly allocated to receive intravenous doses of flumazenil (0.4 mg to 1 mg) or placebo. Levels of sedation and psychomotor impairment were evaluated prestudy, at baseline, and at 6 intervals from 5 to 180 minutes posttreatment. A global evaluation of effectiveness was made at the 5 minute assessment, and memory was assessed at the 180-minute assessment. Flumazenil (mean dose: 0.73 mg [7.3 ml]) was significantly more effective than placebo (mean dose: 8.9 ml) in reversing sedation, psychomotor impairment, and amnesia within 5 minutes after the start of administration. At the 5-minute posttreatment assessment, 84% of 102 flumazenil-treated patients (compared with 42% of 52 placebo-treated patients) experienced complete reversal of sedation. Ninety-two percent of 93 flumazenil-treated patients (compared with 41% of 46 placebo-treated patients) had normal psychomotor function. Reversal of amnesia at the 5-minute assessment was achieved in 75% of 101 flumazenil-treated patients and in 20% of 51 placebo-treated patients. Statistically significant differences between flumazenil and placebo were also observed at the 15-minute assessment. Thereafter there were no significant differences between the two treatment groups. Most (70%) flumazenil-treated patients exhibited no recurrence of sedation during the 180-minute assessment period. The most frequent adverse reaction in the flumazenil group was dizziness (6%). There were no serious adverse experiences related to the test drug. Flumazenil provided prompt, controlled reversal of residual effects, especially sedation, in the majority (84%) of patients recovering from intravenous conscious sedation induced by diazepam. For most (70%) of these flumazenil-treated patients, the reversal was maintained throughout the 180-minute assessment. PMID- 1286498 TI - Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group II. AB - The efficacy and safety of a new benzodiazepine antagonist, flumazenil, were assessed in a double-blind multicenter study. Flumazenil (mean dose, 0.76 mg) or placebo (mean dose, 8.9 ml) was administered intravenously to 130 and 67 patients, respectively, who had been given diazepam in conjunction with an opioid (fentanyl, meperidine, or morphine) for the induction and maintenance of intravenous conscious sedation for diagnostic or therapeutic surgical procedures. The group assessable for efficacy comprised 122 patients treated with flumazenil and 64 patients given placebo. After 5 minutes, 80/115 (70%) flumazenil-treated patients, compared with 21/63 (33%) placebo-treated patients, were completely awake and alert, as indicated by a score of 5 on the Observer's Assessment of Alertness/Sedation Scale. Ninety-five percent of patients in each group who attained a score of 5 at the 5-minute assessment showed no loss of alertness throughout the 180-minute assessment period. Flumazenil-treated patients also performed significantly better on the Finger-to-Nose Test and the recall of pictures shown at the 5-minute assessment. Flumazenil was well tolerated, with no serious adverse effects reported. Thirty-nine (30%) of flumazenil-treated patients, compared with 17 (25%) of placebo-treated patients had one or more drug related adverse experiences. The most common adverse effects were nausea and vomiting in the flumazenil group and nausea and injection-site pain in the placebo group. Flumazenil was found to promptly reverse sedation induced by diazepam in the presence of opioids. PMID- 1286499 TI - Effect of intravenous flumazenil on reversal of the central effects of midazolam used with short-acting opioids for general anesthesia in hospitalized patients: report of a multicenter, double-blind clinical study. The Flumazenil in General Anesthesia in Hospitalized Patients Study Group I. AB - Midazolam, a short-acting benzodiazepine central nervous system (CNS) depressant widely used for the induction and maintenance of general anesthesia, is often supplemented with short-acting opioids for general anesthesia. Administered postoperatively, flumazenil, a specific benzodiazepine antagonist, reverses the CNS sedative effects of midazolam. In a double-blind clinical trial in hospitalized patients, flumazenil, administered postoperatively at an average intravenous dose of 0.89 mg (range: 0.4 mg to 1 mg), was more effective than placebo in reversing sedation and other residual effects of benzodiazepines in patients recovering from general anesthesia induced by midazolam (mean dose 29 mg) in conjunction with fentanyl (mean dose 0.4 mg) or sufentanil (mean dose 0.056 mg). Five minutes posttreatment, 87 (83%) of 124 flumazenil-treated patients and 6 (10%) of 60 placebo-treated patients had attained the criterion response for reversal of sedation. Of these patients, 60% in the flumazenil group, compared with 100% in the placebo group, retained their degree of alertness throughout the 3-hour observation period. Between-group differences were significant until 60 minutes posttreatment, when the effect of the benzodiazepines had spontaneously waned in the placebo group. The Physician's Global Efficacy Rating, providing an overall measure of efficacy 5 minutes after test drug administration, was good or excellent for 86% of the flumazenil-treated patients, as compared with 7% of the placebo-treated patients evaluated. Measurements of psychomotor function and memory also showed significant between group differences. Flumazenil, compared with placebo, was not associated with a substantially greater frequency of operative-site pain. These results demonstrate that the efficacy and safety of flumazenil were not compromised by the addition of a short-acting opioid to the anesthetic regimen. PMID- 1286500 TI - Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia and use of a long-acting opioid in hospitalized patients: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Hospitalized Patients Study Group II. AB - A double-blind clinical trial was conducted to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist, in 146 hospitalized patients, who had had general anesthesia induced by midazolam and a long-acting opioid. Ninety eight patients received flumazenil and 48 received placebo. Administered postoperatively at a mean intravenous dose of 0.84 mg (range: 0.2 mg to 1 mg), flumazenil reversed benzodiazepine-induced sedation to a greater extent than did placebo. At 5 minutes posttreatment, 61 (76%) of 80 flumazenil-treated patients and 7 (18%) of 40 placebo-treated patients had attained a score of 4 or 5 on the Observer's Assessment of Alertness/Sedation Scale, indicating that they were drowsy or fully awake and alert. This level of arousal was maintained for the full 180-minute posttreatment assessment period in 79% of flumazenil-treated patients. Between-group differences in mean change from baseline in level of alertness were statistically significant (P < 0.01) until 60 minutes posttreatment, when the spontaneous recovery of placebo-treated patients resulted in declining intergroup differences. The global efficacy rating (based on the physician's general impression of the effectiveness of the reversal of sedation 5 minutes after test drug administration) was good or excellent in 64 (80%) of the 80 flumazenil-treated patients and 5 (13%) of the 40 placebo-treated patients evaluated. Flumazenil, compared with placebo, was not associated with an increased frequency of operative-site pain, and no serious adverse effects of this benzodiazepine antagonist were reported. The most frequent adverse experiences in both treatment groups were nausea, shivering, and operative-site pain. Vomiting, dizziness, and injection-site reactions were also reported in > or = 5% of patients treated with flumazenil. PMID- 1286501 TI - Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia in outpatients premedicated with an opioid and a muscle relaxant: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Outpatients Study Group II. AB - Flumazenil was studied in a double-blind multicenter trial to confirm its efficacy and safety in antagonizing the central effects of benzodiazepines after general anesthesia (midazolam, short-acting narcotic, nitrous oxide) with muscle relaxants and selected potent volatile anesthetics as needed. One hundred seventy two outpatients were randomly assigned to receive either flumazenil or placebo titrated to the point of reversal of sedation or a maximum dose of 1 mg of flumazenil or 10 ml of placebo. The test drug was given intravenously (0.2 mg flumazenil or 2 ml placebo) at 1-minute intervals. Tests of alertness, psychomotor function, and memory were conducted prestudy and at baseline before the administration of flumazenil and at 5-, 15-, 30-, 60-, 120-, and 180-minute intervals after administration. The changes from prestudy or baseline scores were analyzed to compare differences between treatment groups. Seventy-five percent of the 105 flumazenil-treated patients and 14% of the 55 placebo-treated patients who met the qualifications for efficacy evaluations obtained a criterion level of response as measured by the Observer's Assessment of Alertness/Sedation Scale. Most (76%) patients who were alert at 5 minutes maintained their level of wakefulness throughout the 180-minute observation period. All 172 patients were included in evaluations of safety. Fifty percent of 113 flumazenil-treated patients and 31% of 59 placebo-treated patients reported one or more adverse experiences. The most frequently reported were nausea, vomiting, and dizziness. Only 6 adverse effects in the flumazenil group and 1 in the placebo group were considered severe; the remainder were mild or moderate. None were considered serious or potentially serious. Postoperative administration of flumazenil (mean dose, 0.85 mg) safely provided a prompt, controlled reversal of the sedative and psychomotor effects of midazolam in most patients. PMID- 1286502 TI - Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia in outpatients: a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Outpatients Study Group I. AB - In a US double-blind, multicenter study, flumazenil, a benzodiazepine antagonist, administered postoperatively in a mean intravenous dose of 0.67 mg (range, 0.2 to 1 mg), was superior to placebo in reversing sedation and other central nervous system effects of benzodiazepines in outpatients recovering from general anesthesia induced by midazolam, fentanyl or sufentanil, and nitrous oxide. Within 5 minutes after administration of flumazenil, sedation was reversed in 94% (87 of 93) of flumazenil-treated patients, compared with 13% (6 of 46) of placebo treated patients. The criterion response (Observer's Assessment of Alertness/Sedation Scale score of 4 or 5) that was achieved at 5 minutes was maintained in 79 (93%) of 85 patients throughout the 180-minute observation period. Psychomotor performance, measured by the Finger-to-Nose Test, was rated as normal at 5 minutes posttreatment for 77% (71 of 92) of flumazenil-treated patients, and 4% (2 of 46) of placebo-treated patients. The reversal of amnesia, as determined by the Picture Recall Test was less consistent. Patients given flumazenil did not experience more pain at the operative site or require more analgesic medication than did those given placebo. Nausea (flumazenil 24%; placebo 15%), dizziness (flumazenil 12%; placebo 2%), and vomiting (flumazenil 10%; placebo 9%) were the most frequent adverse effects in each group. In conclusion, flumazenil provided prompt arousal from benzodiazepine-induced sedation and was well tolerated. PMID- 1286503 TI - Treatment of benzodiazepine overdose with flumazenil. The Flumazenil in Benzodiazepine Intoxication Multicenter Study Group. AB - Flumazenil, a specific benzodiazepine antagonist, was evaluated as adjunctive therapy in the management of benzodiazepine overdose. Thirteen emergency departments enrolled 326 patients in this double-blind, placebo-controlled trial; 162 patients were randomly allocated to receive flumazenil (maximum dose, 30 ml, providing 3 mg of flumazenil), and 164 were allocated to receive placebo (maximum dose, 30 ml). A successful response was the attainment of a score of 1 or 2 on the Clinical Global Impression Scale (CGIS), denoting a very much improved or much improved status, 10 minutes after the start of intravenous administration of the test drug. Among those patients whose drug screen revealed the presence of benzodiazepines, 75 (77%) of 97 patients given flumazenil and 13 (16%) of 83 given placebo attained such a response. The mean CGIS score at 10 minutes for benzodiazepine-positive patients treated with flumazenil was 1.95 versus 3.58 for those given placebo. As determined by the Neurobehavioral Assessment Scale, 61% of patients who initially responded became resedated; in these patients, the effect of flumazenil lasted a median of 90 minutes. At the investigator's discretion, patients who did not achieve a criterion response in the double-blind trial could receive open-label flumazenil, titrated as in the double-blind phase. Among the benzodiazepine-positive patients, 9 (53%) of 17 patients from the flumazenil group responded to the additional flumazenil, and 58 (81%) of patients previously given placebo responded. Safety was assessed in all 326 patients given the test drug. The most frequent adverse experiences after the administration of flumazenil were agitation (7%), vomiting (7%), abnormal crying (4%), and nausea (4%); these effects were observed with a lower frequency in the placebo group. Serious adverse experiences were reported in 4 patients; these included seizures and cardiac arrhythmias. Of the 3 patients with seizures, 2 had ingested large doses of cyclic antidepressants in addition to the benzodiazepine. The toxicology screen for 1 of the 2 showed 1900 ng/ml of amoxapine and 900 ng/ml of nortriptyline; the toxicology screen for the other, who also had ventricular tachycardia, showed 1928 ng/ml of loxapine and 301 ng/ml of amoxapine. The results of this study confirm published reports of the efficacy of flumazenil in reversing benzodiazepine-induced sedation in patients with benzodiazepine overdose. This was accomplished irrespective of the presence of coingested drugs. Flumazenil is not recommended for patients with serious cyclic antidepressant poisoning or those who use benzodiazepines therapeutically to control seizure disorders. When used as recommended, however, flumazenil has been shown to have an acceptable safety level. PMID- 1286504 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1286505 TI - Cellular origin of the rapidly exchangeable calcium pool in the cultured neonatal rat heart cell. AB - Calcium in the myocardial cell is highly compartmentalized and in the cultured neonatal rat heart cells over 66% of the exchangeable calcium exchanges extremely fast (t1/2 < 1 s). The goal of the present study was to investigate, in the intact cell, the locus of this pool. By comparing myoblasts and fibroblasts and their respective plasma membranes, it is concluded that in the intact myocyte a significant fraction of the large lanthanum displaceable calcium pool is attributable to intracellular components, not present in the fibroblast. At least 30% of the lanthanum displaceable pool resides intracellularly, as is shown with the use of the drugs nifedipine, ryanodine and thapsigargin. It is proposed that the diadic subsarcolemmal junctional region represents a significant locus for the pool. PMID- 1286506 TI - Dental care and Chicago's working poor. PMID- 1286507 TI - Bringing dentistry to those in need. PMID- 1286508 TI - Preoperative evaluation of the dental patient. PMID- 1286509 TI - Financial turning point. PMID- 1286510 TI - The Americans with Disabilities Act: The other ADA. PMID- 1286511 TI - What a difference a patient makes. PMID- 1286512 TI - Asepsis and sterilization: an old topic brought to life. PMID- 1286513 TI - State and Federal Disability Acts: an overview. PMID- 1286514 TI - Do you know your ADA? PMID- 1286515 TI - Mutual funds for the long haul. PMID- 1286516 TI - Communications Committee. PMID- 1286517 TI - Down's syndrome and the thyroid. PMID- 1286518 TI - Hormonal management of prostate cancer. AB - In advanced disease, androgen deprivation remains the usual treatment. The completion of current trials is awaited to confirm whether total androgen blockade will prolong survival. To make further advances in treatment the fundamental biology of the prostate cell, benign or malignant, and its relationship to endocrine manipulation, must be understood. This may then lead to an understanding of clonal escape mechanisms in transformed cells and the clinical correlate of escape, relapse. PMID- 1286519 TI - Morbidity in patients on L-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH. AB - OBJECTIVE: Patients on L-thyroxine with a 'suppressed' TSH (< 0.05 mU/l) were compared to those in whom TSH was detectable but not elevated (0.05-4.0 mU/l), with regard to morbidity data. DESIGN: Biochemical data from Tayside Thyroid Register was matched to hospital admissions data obtained from Health Board Statistics. PATIENTS: The patients were identified from those registered on the computerized Tayside Register. MEASUREMENTS: Serum T4 and TSH assays, clinical assessment scores, and admission records with regard to ischaemic heart disease, overall fractures, fractured neck of femur and breast carcinoma. RESULTS: Over one year, 1180 patients on thyroxine replacement had clinical and biochemical assessment; 59% had a suppressed TSH and 38% 'normal' TSH. Patients with a suppressed TSH exhibited higher median serum thyroxine levels (146 nmol/l, range 77-252 vs 119 nmol/l, 58-224; P < 0.001). Patients under the age of 65 years on L thyroxine had an increased risk of ischaemic heart disease compared to the general population (female 2.7 vs 0.7%, P < 0.001; male 6.4 vs 1.7%, P < 0.01), but the risk was no different between those with suppressed and normal TSH. There was no increase in risk for overall fracture, fractured neck of femur or breast carcinoma in those on thyroxine with suppressed or normal TSH. CONCLUSION: Patients under the age of 65 years on L-thyroxine had an increased risk of ischaemic heart disease. There was no excess of fractures in patients on L thyroxine even if the TSH is suppressed. PMID- 1286520 TI - Circadian changes in pulsatile TSH release in primary hypothyroidism. AB - OBJECTIVE: We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism. DESIGN: In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured. SUBJECTS: Nine patients with overt primary hypothyroidism, seven patients with subclinical hypothyroidism and 16 healthy controls. MEASUREMENTS: Computer-assisted analysis by the Desade and Cluster programs. RESULTS: Both computer-assisted programs revealed an increased TSH pulse amplitude in both overt and subclinical hypothyroidism versus controls (Desade: 36.9 +/- 31.4 (mean +/- SD) (P < 0.001) and 2.8 +/- 1.9 (P < 0.001) vs 0.4 +/- 0.2 mU/l; Cluster: 25.6 +/- 25.1 (P < 0.001) and 2.4 +/- 1.4 (P < 0.001) vs 0.4 +/- 0.2 mU/l). TSH pulse frequency remained unchanged with approximately 10 pulses/24 hours. A highly significant correlation was found between the mean 24-hour TSH concentration and the TSH pulse amplitude in all controls and patients but not to TSH pulse frequency. The nocturnal TSH surge was absent in six out of nine patients with overt primary hypothyroidism. The deficient nocturnal rise of TSH in primary hypothyroidism vs controls (22 +/- 51 vs 82 +/- 41%, P < 0.001), was associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency. CONCLUSIONS: Mean 24-hour TSH pulse amplitude is increased in primary hypothyroidism, but TSH pulse frequency remains unchanged. The decrease of the nocturnal TSH increase in primary hypothyroidism is associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency. PMID- 1286521 TI - Circadian rhythm and pulsatility of parathyroid hormone secretion in man. AB - OBJECTIVE: We wished to investigate the circadian rhythm and pulsatility of parathyroid hormone (PTH) secretion in man, as conflicting results have been published. DESIGN AND PATIENTS: To investigate the circadian rhythm during daytime, we sampled (a) peripheral blood at hourly intervals in 12 healthy young men from 0900 h until 1700 h. For observation of pulsatility, we sampled (b) peripheral blood at 1-minute intervals for 1 hour in three healthy men and three healthy women (mean 27.7 years, range 21-56 years) and (c) at 1-minute intervals for 30 minutes in 21 patients with surgically confirmed primary hyperparathyroidism (pHPT). MEASUREMENTS: The serum levels of intact PTH were measured by two-site immunoradiometric assay and special care was taken to reduce intra-assay variability, especially at the normal PTH concentration. In series (a), ionized calcium, total calcium and phosphate were also determined. RESULTS: A circadian rhythm during daytime was found for intact PTH in healthy men and women with a nadir at 0930 h and a peak in the afternoon. Ionized calcium and total calcium (protein-adjusted) decreased and phosphate increased in the afternoon. These changes were all statistically significant (P < 0.02). Pulsatility of PTH: Statistical cluster analysis of the data showed no pulsatility either in healthy persons or in patients with primary hyperparathyroidism. In two healthy women and one healthy man slight changes of longer duration were discovered, but no complete pulses. In five patients with primary hyperparathyroidism, larger differences between the highest and lowest concentrations of intact PTH were found, but no complete pulses. CONCLUSIONS: Our data show a significant circadian rhythm during daytime of intact PTH and only minor changes from minute to minute. The alterations in PTH-levels occurred at longer time intervals in healthy persons. In some patients with primary hyperparathyroidism, decreases of PTH-levels were found. The circadian rhythm of PTH may be due to slight changes in calcium or phosphate concentration. PMID- 1286522 TI - The effects of opioid blockade and GnRH administration upon luteinizing hormone secretion in patients with anorexia nervosa during the stages of weight loss and weight recovery. AB - OBJECTIVE: We examined the functional status of the hypothalamic-opioid system involved in LH secretion and the pituitary LH sensitivity and reserve in patients with anorexia nervosa were studied during body weight loss and weight recovery. We measured the temporal relationship between weight recovery, expression of hypothalamic-opioid activity and pituitary GnRH responsiveness, and resumption of ovulatory cycles. DESIGN: Five patients with anorexia nervosa were prospectively studied during weight loss and amenorrhoea, subsequently when they reached their ideal body weight but still remained amenorrhoeic and thereafter every 6 months until resumption of ovulatory cycles; one patient was studied only during weight loss, two during ideal body weight and amenorrhoea and one during ideal body weight and ovulatory cycles. Blood was sampled every 10 minutes over a 16-hour period on two alternate days. On study day 1 (control day), patients received two sets of saline infusion every 6 hours and one saline bolus at the beginning of the seventh hour; on study day 3 (experimental day), they received a saline infusion during the first 6 hours, an intravenous bolus of naloxone (20 mg) at the beginning of the seventh hour and then a continuous naloxone infusion (1.6 mg per hour) during the ensuing 6 hours. Pituitary LH sensitivity and reserve were assessed on both study days by the subsequent administration of 5 and 95 micrograms of GnRH 4 hours before the completion of each sampling period. Patients in ideal body weight and ovulatory cycles as well as five normal menstruating women included in the study for comparative purposes, were studied during the midluteal phase of a cycle. MEASUREMENTS: LH, oestradiol and progesterone were determined by radioimmunoassay. Areas under the LH curve were calculated by the trapezoid method; LH pulse detection was carried out by the program Cluster. RESULTS: Naloxone administration to patients with anorexia nervosa in the weight loss phase, did not significantly modify their serum LH levels nor the characteristics of its pulsatile secretion. Administration of the opioid blocker induced a significant increase in serum LH concentrations only in those patients in ideal body weight and amenorrhoea who resumed ovulatory cycles within the 6 months following the last study as well as in patients with an ideal body weight and ovulatory cycles and in normal controls. All patients and subjects who responded to naloxone administration exhibited significant increases in the area under the LH curve, mean LH pulse amplitude and peak area. Patients in ideal body weight and amenorrhoea who did not resume ovulatory cycles within the 6 months following the study days, did not respond to naloxone administration. There were no significant correlations between the magnitude of LH response to naloxone administration and the baseline levels of serum oestradiol and progesterone. All patients exhibited significant pituitary LH responses to both GnRH doses, regardless of the stage of the disease; however, the pituitary responsiveness shown by patients in ideal body weight was significantly higher than that presented by patients in weight loss. There were no significant differences between the responses to GnRH exhibited by patients in ideal body weight and amenorrhoea who responded to naloxone administration and those shown by patients in the same clinical condition but who were insensitive to opioid blockade. CONCLUSIONS: The re-establishment of hypothalamic-opioid inhibitory activity involved in LH secretion in patients with anorexia nervosa during the phase of weight gain predicts imminent restoration of ovulatory cycles. Pituitary LH response to exogenous GnRH during weight recovery does not accurately predict the outcome of the disease regarding reinitiation of menstrual cycles; however, it might be an indicator that the normal function of the hypothalamic-pituitary axis is being restored. PMID- 1286523 TI - The empty sella: results of treatment in 76 successive cases and high frequency of endocrine and neurological disturbances. AB - OBJECTIVE: We assessed the frequency of endocrine or neurological disturbances and the results of surgery in patients with empty sella, diagnosed with cisternography and/or computerized tomography scanning. DESIGN AND PATIENTS: Analysis of hospital records of 76 successive patients (73 primary, three secondary empty sella) from a single institution. MEASUREMENTS: Clinical and neuro-ophthalmological evaluation. Serum PRL, GH, TSH, LH, FSH, T4, T3 by radioimmunoassay. Diagnosis of empty sella with cisternography and/or computerized tomography scanning (n = 69), or discovered at surgery (n = 7). RESULTS: Patients with empty sella had: headache (69.7%), visual disturbances (34.2%), cerebrospinal fluid rhinorrhoea (11.8%), endocrine disturbances (51.4%, including hyperprolactinaemia, acromegaly, Cushing's syndrome). A pituitary tumour was discovered in two patients, in seven other ones it was suspected but not found at surgery. Transsphenoidal packing of empty sellas was done in 56 cases, with 7.1% post-operative complications. With surgery there was improvement of headache in 71%, of visual disturbances in 46%. Cerebrospinal fluid rhinorrhoea (discovered at surgery in four other patients) was not resolved by the first operation in six out of 13 patients. In 20 patients without surgery, headache improved in 64.6%. CONCLUSIONS: The empty sella is frequently associated with a variety of neurological and endocrine disturbances, which is contrary to conventional belief. Cerebrospinal fluid rhinorrhoea is not a rare complication and it may be difficult to treat. Some cases of empty sella may be due to partial pituitary apoplexy. Autoimmunity may have existed in other cases. Surgery may be useful in many patients, but a judicious selection is needed because it entails complications and non-operated patients may improve spontaneously. PMID- 1286524 TI - Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group. AB - OBJECTIVE: Dopamine agonists have a well established place in the treatment of hyperprolactinaemic disorders but their use is associated with a high incidence of adverse effects. We have investigated the biochemical efficacy and side-effect profile of a range of doses of the novel, long-acting dopamine agonist, cabergoline, in suppressing prolactin (PRL) in hyperprolactinaemic women. DESIGN: Multicentre, prospective, randomized, placebo controlled and double blind. PATIENTS: One hundred and eighty-eight women with hyperprolactinaemia secondary to microprolactinoma (n = 113), idiopathic disease (n = 67), empty sella syndrome (n = 7) or following failed surgery for a macroprolactinoma (n = 1). MEASUREMENTS: Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function. RESULTS: Patients received either placebo (n = 20) or cabergoline 0.125 (n = 43), 0.5 (n = 42), 0.75 (n = 42) or 1.0 mg (n = 41) twice weekly for 4 weeks. The five treatment groups were comparable in age (mean 31.8, range 16-46 years), diagnosis, previous therapy, and pretreatment serum PRL. PRL was suppressed to below half the pretreatment level in 5, 60, 90, 95 and 98% and normalized in 0, 30, 74, 74 and 95% of patients taking placebo or cabergoline 0.125, 0.5, 0.75 or 1.0 mg twice weekly respectively (Armitage's test, chi 2 = 39.3, P < 0.01). Cabergoline therapy (all doses) restored menses in 82% of the amenorrhoeic women not previously treated with dopamine agonists. Adverse events were recorded in 45% of patients in the placebo group and in 44, 50, 50 and 58% of those taking 0.125, 0.5, 0.75 and 1.0 mg cabergoline twice weekly (Armitage's test, P > 0.05). Over 95% of reported symptoms were relatively trivial, most frequently transient nausea, headache, dizziness, fatigue and constipation. More severe adverse events, interfering significantly with the patients' lifestyle, occurred in 13 (7.7%) patients taking cabergoline; treatment withdrawal was necessary in only one case. No adverse effects were detected on blood pressure or haematological or biochemical parameters. CONCLUSIONS: We have shown a linear dose-response relationship for cabergoline in the treatment of hyperprolactinaemia in the range 0.125-1.0 mg twice weekly, with normalization of PRL in up to 95% of cases and acceptable tolerability throughout the dose range. PMID- 1286525 TI - Immunoreactive inhibin levels during ovarian stimulation may predict granulosa cell maturity. AB - OBJECTIVE: The aim of the study was to assess whether the immunoreactive inhibin response to ovarian stimulation in polycystic ovarian syndrome was of predictive value for the outcome of ovulation induction. DESIGN: Daily injections of purified FSH (Metrodin, Serono Laboratories, UK) were administered for the purpose of inducing development and ovulation of a single follicle. PATIENTS: All patients had anovulatory infertility secondary to polycystic ovarian syndrome and were resistant to clomiphene citrate. MEASUREMENTS: Alternate day serum samples were obtained for measurement of gonadotrophins, sex steroids and inhibin by radioimmunoassay. Alternate day ovarian ultrasound scans were carried out to monitor follicular development. RESULTS: There was a high incidence of multiple follicular development (MFD) (10.2 +/- 7.1 (standard deviation) follicles). There was a close relationship between the number of follicles on the day of the ovulatory trigger and serum oestradiol (E2) levels (R = 0.97, P < 0.001). This relationship was not seen with serum immunoreactive inhibin levels (R = 0.31). The cycles were divided into two groups depending whether there was or was not MFD (more than five follicles > 7 mm in diameter on day of hCG administration). The MFD group had 15.6 +/- 8.5 follicles and the non-MFD group 3.2 +/- 1.6 follicles. There was no difference in the circulating E2 concentration (pmol/l) per follicle between the two groups (non-MFD cycles, n = 6,345 +/- 28.9; MFD cycles, n = 8, 308 +/- 40.29). However, the immunoreactive inhibin concentration (U/ml) per follicle was lower, P < 0.001, in the MFD group (4.3 +/- 1.6 vs 6.9 +/ 0.5). The maximum and mean follicle diameter were lower, P < 0.01, in the MFD group (maximum follicle size 16.5 +/- 3.9 vs 21.2 +/- 1.5 mm, mean follicle size 11.5 +/- 2 vs 14.9 +/- 2.3). When individual cycles were examined E2 and immunoreactive inhibin secretion rose in parallel in cycles with less than five follicles with a rapid rise occurring when the follicles reached about 12 mm in diameter. In cycles where there was MFD there was a disparity between E2 and immunoreactive inhibin secretion with E2 levels rising 4.3 +/- 1.4 days before immunoreactive inhibin levels. CONCLUSION: These data suggest that in cycles where there are multiple small follicles, E2 secretion is maintained whereas immunoreactive inhibin secretion is substantially lower. Thus, in view of the disparity between E2 and immunoreactive inhibin secretion evident in the MFD group, measurement of immunoreactive serum inhibin concentration may be a better indicator of granulosa cell maturity. Immunoreactive inhibin secretion may occur only from healthy mature follicles. PMID- 1286526 TI - Human chorionic gonadotrophin contributes to the bioactivity of Pergonal. AB - OBJECTIVE: We examined batch variation in the LH-like bioactive content of Pergonal and determined whether hCG contributes to this. DESIGN: Random selection of three batches of Pergonal, consisting of three ampoules in each batch. MEASUREMENTS: The LH content in each ampoule was determined by radioimmunoassay (R-LH), immunoradiometric assay (I-LH) and in vitro Leydig cell bioassay (B-LH) using the urinary hMG International Standard 70/45. Human chorionic gonadotrophin was determined by immunoradiometric assay (I-hCG) using the hCG IRP 75/537. The isohormone content of each batch was examined by chromatofocussing over the range pH 4.5-7.0 and the fractions collected were assayed for LH and hCG content. The variability in potency between batches was assessed by single factor analysis of variance. RESULTS: The gonadotrophin content of each batch (IU/ampoule, mean +/- SEM, n = 3 ampoules) was R-LH (40.9 +/- 0.5, 40.8 +/- 0.2, 39.3 +/- 0.7, P > 0.15), I-LH (39.0 +/- 1.5, 28.3 +/- 0.8, 36.9 +/- 3.3, P < 0.001), B-LH (27.3 +/- 0.3, 12.0 +/- 0.9, 19.3 +/- 0.9, P < 0.001) and I-hCG (16.4 +/- 0.7, 11.7 +/- 0.2, 10.5 +/- 0.5, P < 0.001). The chromatofocussing recoveries below pH 5.5 expressed as a percentage of the total amount of analyte eluted from the column and collated for all three batches of Pergonal were (mean % +/- SD, n = 3 batches) R-LH (58.4 +/- 4.0), I-LH (41.3 +/- 7.5), B-LH (81.4 +/- 2.8) and I-hCG (87.8 +/- 3.7). CONCLUSIONS: There was significant batch variation in the I-LH, B LH and I-hCG (P < 0.001) but not the R-LH (P > 0.15) content of Pergonal. More than 80% of the total B-LH recovery chromatofocussed below pH 5.5 and corresponded to the region of highest I-hCG (> 87%) and lowest I-LH (< 42%) recovery. This was highly suggestive of hCG contributing to the LH-like bioactivity of Pergonal. PMID- 1286527 TI - Non-autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism. AB - A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life-threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid-region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non-calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set-point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient. PMID- 1286528 TI - Thyroid abscess complicating subacute thyroiditis: a consequence of steroid therapy? AB - A patient with subacute thyroiditis developed a thyroid abscess after drainage of a pilonidal abscess. An infective focus in a patient with subacute thyroiditis on steroids should be treated aggressively with adequate antibiotic cover. PMID- 1286529 TI - Effect of potassium infusion on renal function in ANF-transgenic mice. AB - Transgenic mice expressing an ANF fusion gene in the liver were used to study renal function before and during an intravenous KCl load. These animals are characterized by a 10- to 20-fold elevation in plasma ANF concentration, and by a reduction in arterial blood pressure by 20-30 mm Hg, compared to nontransgenic littermates. Before the KCl infusion, renal excretions of fluid, sodium, potassium, and chloride were not different from corresponding values in the nontransgenic sibling mice. Glomerular filtration rates were slightly lower in the transgenic animals. During the KCl infusion, diuresis, saluresis, and kaliuresis were found in both groups. However, salt and water excretion, but not potassium excretion, were significantly greater in the transgenic group. In a separate series, plasma aldosterone concentrations were significantly higher in the transgenic, compared to the nontransgenic mice. These data are interpreted as indicating that antinatriuretic mechanisms, including aldosterone-dependent sodium reabsorption in the cortical collecting tubule, can counteract the effect of ANF to inhibit sodium reabsorption in the medullary duct system, thus allowing maintenance of salt balance. Furthermore, a reduced tubular flow rate at the aldosterone-sensitive site would ensure normal potassium excretion despite the elevated mineralocorticoid level. During KCl infusion, the known increase in tubular delivery of salt and water to the duct would allow full expression of the downstream ANF effect, accounting for the relatively greater diuresis and saluresis in the transgenic mice. We conclude that both renal and adrenal actions of ANF can be rendered ineffective by countervailing mechanisms, suggesting an explanation for the apparent lack of biological activity of endogenously elevated plasma NAF in some disease states. PMID- 1286530 TI - Definition of a small chromosomal rearrangement on chromosome 11p14 by molecular cytogenetics in situ hybridization. AB - Chromosomal in situ hybridization allows the detection and the definition of single copy DNA segments of very small size. In a particular case, we demonstrate the inactivity of this molecular cytogenetic technique. In this case, karyotype analysis revealed a chromosome 11p+. In situ hybridization of probes PBGD, D11S29, NCAM, and ETSI located at 11q23-qter shows that the extra chromosomal material on chromosome 11p+ is a duplication of the 11q23-qter region. PMID- 1286531 TI - Evidence for T lymphocyte reactivity to the 65 kilodalton heat shock protein of mycobacterium in active Crohn's disease. AB - The role of mycobacterial heat shock proteins (Hsp) of the 65 kilodalton Hsp family as a possible factor governing cell-mediated immune responses, leading to chronic mucosal inflammation, was examined. Purified peripheral blood mononuclear cells (PBMC) from patients with CD and ulcerative colitis (UC), and from healthy and disease controls were stimulated in culture with a highly purified, recombinant 65 kilodalton Hsp (rHsp65) of M. bovis BCG for 5 d. Cultures were then pulsed with 3H-thymidine for 24 h and uptake determined by liquid scintillation. We found that PBMC from patients with active CD exhibited a significant proliferative response to the soluble rHsp65 as compared with normal controls. In contrast, the proliferative responses of PBMC from patients with inactive CD, inactive and active UC, pancreatitis and cecal carcinoma were found to be not different from controls. Purified T cells or non-T cells of PBMC in the absence of antigen-presenting cells from active CD patients exhibited a lack of proliferative responses to the rHsp65 stimulation in culture. The data indicate an aberrant sensitization of T cells to the 65 kilodalton mycobacterial Hsp in a specific type of IBD, and thus may provide an important clue for the etiopathogenesis of Crohn's disease. PMID- 1286532 TI - A pilot study of steroid withdrawal followed by oral acyclovir in the treatment of chronic type B hepatitis. AB - Ten patients with chronic type B hepatitis were treated for four weeks with a rapidly tapered dose of oral prednisone (initial dose, 40 mg/d) followed by two weeks of no therapy followed by four weeks of oral acyclovir (600 mg/d). Liver biochemistry, HBsAg, HBeAg, DNA-polymerase and HBV-DNA levels in serum were determined prior to, during and for six months following therapy. The mean age +/ SD of the study population was 33 +/- 15 years (range 18-58). Nine of the patients were male. Four patients were Caucasian and six of Southeast Asian origin. Three patients were homosexual, all HIV antibody negative. The mean ALT level prior to treatment was 89 +/- 62 IU/L (range: 30-214). During the six month post-treatment follow-up period, 5/8 (63%) patients became DNA-P negative and 6/10 (60%) HBV-DNA negative. One responder reverted to DNA-P positive (final response, 50%) and another to HBV-DNA positive (final response, 50%) prior to completion of the study. Patients were more likely to become DNA-P or HBV-DNA negative if they had elevated pre-treatment ALT values and low levels of DNA-P and HBV-DNA. HBeAg became undetectable in 3/10 (30%) individuals, one of whom reverted to positive at the end of the follow-up period (final response, 20%). All patients remained HBsAg positive. Mild fatigue, which occurred in four individuals, was the most common side effect. The results of this study suggest that a controlled clinical trial of oral prednisone/acyclovir is warranted in the treatment of adults with chronic type B hepatitis. PMID- 1286533 TI - The quality of medical science. AB - Is the quality of science aimed at understanding and treating disease inferior to more basic investigations of basic biology, or does the different quality of medical science reflect a distinct nature? This duality in the meaning of quality is central to any critique of the quality of medical science. The nature of medical science, which deals with the dysfunction of integrated genetic, epigenetic, environmental, or stochastic phenomenon, is distinct from that of basic science which seeks to describe discrete biological processes. In physical sciences it is generally accepted that there are practical boundaries between disciplines such as quantum physics, thermodynamics, and chemistry even though, in theory, such investigations are related. In meteorology, the development of chaos theory establishes that there are even theoretical limits to the ability to predict large scale processes from their essential, constituent processes. So too, the quality of medical science may be distinct from that of basic biology. PMID- 1286534 TI - Prospects for academically trained pediatricians in academic medicine. AB - There is widespread concern about the commitment and ability of physicians to enter careers in academic medicine. We studied MEDLINE citations by 150 academically trained pediatricians to determine whether they remained in academic medicine and to assess the nature of their contribution. We identified 2098 citations by 122 of the 150 individuals which reflected substantive involvement in clinical and basic research. Most individuals published their first papers within three years after residency and thereafter exhibited a stable level of productivity. Individuals who published prior to completing residency were most likely to enter academic medicine and achieve a high level of productivity. These reassuring data suggest that individuals who pursue an academic track may assume the traditional role of the physician scientist, and suggest measures which may be taken to attract more physicians to academics. PMID- 1286535 TI - Twenty years of randomized clinical trials of manipulative therapy for back pain: a review. AB - Manipulative therapy has been one of the most intensively studied approaches to back pain management. This paper reviews 20 years of randomized clinical trials of manipulative therapy, and addresses the following issues: for what condition were these patients treated? What was the population studied, and were workers included? Was a specific technique, spinal manipulation, or a more global approach the object of the trial? Finally, were there long-term outcome measures? The 21 randomized clinical trials reviewed here provide some indication that manipulative therapy offers some positive short-term results; it is not clear at this point whether long-term effects of the treatment have been adequately evaluated. Lack of specificity in the description of samples makes it impossible to conclude on the benefit of spinal manipulation for workers. Whether manipulation is solely responsible for the changes mentioned in these studies, independently of the global approach put forth by its practitioners, is also an open question that awaits further study. PMID- 1286537 TI - Mission and accountability of academic health science centres. PMID- 1286536 TI - Brighter prospects for academic medicine. PMID- 1286538 TI - Challenging consults: application of principles of physiology and biochemistry to the bedside. A case with marked hyperglycemia. PMID- 1286539 TI - Correlation of morphometric analysis of pancreatic islets and diabetes in spontaneously diabetic BB/W rats. AB - Morphometric analysis of pancreatic islets was performed on BB/W rats, which were divided into moderately diabetic and severely diabetic as well as normoglycemic during four months of observation. In normoglycemic rats, total islet area occupied 1.2% of total pancreatic tissue area with a mean area of 19,000 microns2 per islet. Total pancreatic area was markedly decreased to 22% and 10% in moderately and severely diabetic rats, respectively, compared with that of normoglycemic rats. Mean islet area of moderately and severely diabetic rats decreased to 28% and 25% per islet that of normoglycemic rats, respectively, in which severely diabetic rats showed variable sizes of islets. Concomitant morphometric analysis of renal glomeruli showed decreasing sizes of glomeruli in severely diabetic rats whereas number of glomeruli in renal cortex increased in severely diabetic rats compared with normoglycemic rats. Moderately and severely diabetic states were also studied by I.V. glucose and insulin tolerance tests in regard to plasma glucose and insulin levels compared with normoglycemic rats. During months of observation severely diabetic rats had their total islet area reduced to 10% that of normoglycemic rats as a result of cell mediated immune destruction of islets. And concomitant reduction of glomeruli may be a part of diabetic glomerulopathy. Yet, diabetic rats were normotensive. The degree of water intake, urine volume, urine glucose, urine protein and albumin was also correlated with the degree of diabetes. This study further provides the feasibility of using diabetic BB/W rats for diabetic conditions and their complications. PMID- 1286540 TI - Prediction of insulin dependent diabetes mellitus in non-obese diabetic mice by the endogeneous tumor necrosis factor-alpha level. AB - The non-obese diabetic (NOD) mouse is an animal model of human insulin dependent diabetes mellitus (IDDM). In this strain, the serum concentration of tumor necrosis factor-alpha (TNF alpha) after OK432 (a streptococcal preparation) stimulation is much lower than in any other non-diabetic control strain. Female NOD mice which have a higher incidence of diabetes have significantly lower TNF alpha level (6.5 +/- 4 U/ml, mean +/- SEM) than do male NOD mice (21 +/- 5 U/ml) (P < 0.02) which have lower incidence of diabetes. On the basis of these results, we designed a prospective study to evaluate the relationship between the serum TNF alpha concentration and the incidence of diabetes in individual male NOD mice. Mice were studied until 30 weeks of age. During this period four of eight mice with a low TNF alpha level (TNF alpha < or = 1.1 U/ml) became diabetic, whereas none of eighteen mice with a high TNF alpha level (TNF alpha > 1.1 U/ml) developed overt diabetes. These results indicate that by measuring of endogeneous TNF alpha level after stimulation by OK432, one could predict IDDM in male NOD mice. PMID- 1286541 TI - Insulin, glibenclamide or metformin treatment for non insulin dependent diabetes: heterogenous responses of standard measures of insulin action and insulin secretion before and after differing hypoglycaemic therapy. AB - Using carefully selected relatively non-obese non insulin dependent diabetic patients, we were not able to show differences in standard measures of insulin production or insulin action between patients treated with a long acting crystalline zinc insulin, with glibenclamide, or with metformin for a six week period. All three drugs were hypoglycaemic, but a fall in basal hepatic glucose output measured by the 3H3 glucose technique was only seen in those patients who had an initial fasting plasma glucose above 12.0 mmol/l, irrespective of treatment. PMID- 1286542 TI - Influence of blood glucose levels on peripheral lymphocytes in patients with diabetes mellitus. AB - Abnormalities in lymphocyte subpopulations in patients with type 1 diabetes have been reported previously. To evaluate the effect of blood glucose levels on peripheral lymphocyte concentrations we studied the proportion and phenotypic composition of the T-cell population in 7 patients with type 1 and in 12 patients with type 2 diabetes at hospitalization because of metabolic dysregulation and in a period of restored control. Both the number of CD-4 and CD-8 positive cells increased significantly (p < 0.05), although no change in the CD-4:CD-8 ratio was observed. After restoring metabolic control there was a significant rise in the mean number of total lymphocytes (1760 +/- 759 x 10(6)/ml vs 2385 +/- 889 x 10(6)/ml, p < 0.05). The number of total lymphocytes increased in all patients but one. It is concluded that metabolic control can influence immunological parameters such as numbers of peripheral lymphocytes of various phenotypes. PMID- 1286543 TI - Growth hormone levels in the basal state and after thyrotropin-releasing hormone stimulation in young type 1 (insulin-dependent) diabetic patients with severe retinopathy. AB - Sixteen young patients with type 1 diabetes mellitus and rapidly progressive severe retinopathy were examined regarding serum levels of growth hormone before and after the i.v. administration of 200 micrograms thyrotropin-releasing hormone (TRH). Serum IGF I, HbA1c, blood pressure, urinary albumin, and serum creatinine levels were also measured. The control group consisted of type 1 diabetic patients matched for age, duration of diabetes and metabolic control with no or minimal background retinopathy. The results show that basal growth hormone levels were above normal in both groups, and that there was a paradoxical increment in growth hormone levels after TRH stimulation (p < 0.05) in patients with severe retinopathy, but the values did not differ from patients with background retinopathy. IGD I levels were normal in all patients but one, and no differences were seen between the two groups. HbA1c, serum creatine, blood pressure, and urinary albumin levels were similar in the groups but patients with severe retinopathy were treated with more insulin (p < 0.001). Thus, neither abnormal growth hormone levels, nor IGF I, seems to be associated with the development of severe retinopathy in young type 1 diabetic patients. PMID- 1286544 TI - Delayed replication of human umbilical vein endothelial cells in high glucose is corrected by L-tyrosine. AB - Human umbilical vein endothelial cells (HUVEC) cultured in high glucose exhibit delayed replication and colchicine-resistant microtubules. Tubulin dysfunction and stabilization, brought about by acetylation of the NH2-terminal residues, loss of the C-terminal tyrosine and binding of microtubular-associated proteins (MAPs) may be involved in the above phenomenon. The effects of L-tyrosine on HUVEC replication in high glucose were tested and the hypothesis that non enzymatic glycosylation might impair tubulin depolymerization was also checked by growing the cells in the presence of L-glucose, which binds to intracellular proteins but remains metabolically inactive. After 18 days in culture, the number (mean +/- SEM, n = 7) of HUVEC grown in 28.0 mmol/l D-glucose (435.7 +/- 59.1 x 10(3)) was lower than in 5.6 mmol/l D-glucose (818.3 +/- 75.2 x 10(3)), p < 0.0001. The addition of L-tyrosine 1.7 mmol/l corrected such growth inhibition (623.3 +/- 81.7 x 10(3)), p < 0.0001 vs. D-glucose 28.0 mmol/l, but the cells recovered were less numerous than in physiological glucose alone (p = 0.016). The addition of L-tyrosine to D-glucose 5.6 mmol/l (731.0 +/- 63.2 x 10(3)) did not modify the cell number significantly. HUVEC in extra L-glucose (687.4 +/- 72.0 x 10(3)) were less numerous than in 5.6 mmol/l D-glucose, p = 0.028, but more than in D-glucose 28 mmol/l, p < 0.0001, and were not modified by the addition of L tyrosine (729.4 +/- 67.1 x 10(3)). HUVEC grown in physiologic and high glucose exhibited specific immunofluorescence for acetylated tubulin and MAPs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286545 TI - A comparison of four methods for assessing in vivo beta-cell function in normal, obese and non-insulin-dependent diabetic man. AB - Several methods of varying complexity are available for the measurement of in vivo insulin secretion in man. No study has previously compared these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared four methods for measuring insulin secretion in man: Hyperglycaemic clamp (Hy), Minimal model (MIN), shortened intravenous glucose tolerance test (IVGTT) and continuous infusion of glucose with model assessment (C.I.G.M.A.). Seventeen subjects with varying degrees of insulin sensitivity were studied. Seven normal (BMI 22.5 +/- 1.5 kg/m2), five obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomised fashion, on separate days. First (PSI) and second phase (PSII) rate constants (MIN); incremental insulin secretion 0-10 mins (Hy delta I) and steady state insulin levels from the last 30 minutes (Hy120-150) from the hyperglycaemic clamp; 3 minute insulin concentration and incremental area under insulin secretion curve 0-10 min (IVGTT) and beta-cell function (%) from C.I.G.M.A. were used as indicators of insulin secretion. Each index of insulin secretion could detect an overall difference between the groups. Insulin secretion in normals and obese was similar but significantly increased compared to NIDDM. In normals PSI correlated with C.I.G.M.A. (Rs = 0.92, p < 0.02) and Hy120-150 (Rs = 0.82, p < 0.05). IVGTT0-10 correlated with PSII (Rs = 0.83, p < 0.05), HY delta I (Rs = 0.84, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.001). In obese PSII correlated with C.I.G.M.A. (Rs = 0.91, p < 0.05), Hy delta I (Rs = 1.0, p < 0.02) Hy120-150 (Rs = 0.92, p < 0.05) and IVGTT3 min Rs = 1.0, p < 0.02). In addition Hy delta I also correlated with C.I.G.M.A. (Rs = 0.92, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.02). In NIDDM Hy delta I correlated with C.I.G.M.A. (Rs = 0.91, p < 0.005). When all subjects from the three groups were combined, significant positive correlations were obtained between each index of insulin secretion. In conclusion we have demonstrated that: (a) C.I.G.M.A., IVGTT, Minimal model and hyperglycaemic clamp can provide similar overall results for, in vivo, beta-cell function in man. (b) Significant positive correlations were obtained between each index of insulin secretion when all subjects were combined. (c) Using the above methodologies insulin secretion in normal and obese appears similar but significantly increased compared to NIDDM subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1286546 TI - Pancreastatin inhibits insulin secretion from isolated rat islets: studies on its mechanism of action. AB - The peptide pancreastatin is known to inhibit insulin secretion. To study its mechanism of action, we examined the effects of pancreastatin on 45Ca(2+)- and 86Rb(+)-efflux from isolated rat islets. We found that glucose (8.3 mmol/l) stimulated insulin secretion was totally abolished by pancreastatin (100 nmol/l). It is known that glucose reduces the 86Rb(+)-efflux and increases the 45Ca(2+) efflux from prelabelled islets, which reflects its action on the K(+)- and Ca(2+) permeabilities. We found that pancreastatin reduced the glucose-stimulated increase in 45Ca(2+)-efflux without affecting the 86Rb(+)-efflux. This shows that pancreastatin inhibits the action of glucose on Ca(2+)-channels, without influencing the closure of K(+)-channels induced by the sugar. The results indicate that pancreastatin does not inhibit insulin secretion by hyperpolarizing the B-cells, but rather that the peptide inhibits insulin secretion by inhibiting the glucose-stimulated B-cell Ca(2+)-uptake that evolves by depolarization. PMID- 1286547 TI - Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo controlled study with nitrendipine in borderline hypertensive patients with IDDM type diabetes mellitus. AB - Twenty-nine IDDM patients with borderline hypertension were randomly allocated to placebo or nitrendipine treatment. Nitrendipine was given orally at a dosage of 20 mg once daily over 4 weeks. Stimulated platelet thromboxane formation at rest and after standardized, non exhausting exercise was measured by standard methods. In addition, plasma levels of platelet factor 4 and aggregation responses to collagen and ADP were determined. In the treatment group thromboxane formation after stimulation with collagen (0.3 and 1.0 micrograms/ml) and 1 mM arachidonic acid (AA) was reduced in the resting state. Exercise induced change of thromboxane synthesis in response to 1.0 micrograms/ml collagen was significantly lower as compared to placebo (p < 0.05). In parallel, PF4 plasma levels were significantly lowered (p < 0.05). Whole blood aggregation after collagen stimulation (1.0 micrograms/ml) was reduced after 4 weeks of nitrendipine treatment, but ADP (5 microM) induced aggregation was not. These effects of nitrendipine were not seen in platelet rich plasma. In conclusion long-term nitrendipine treatment may inhibit collagen dependent platelet activation in the blood of diabetic patients with borderline hypertension. PMID- 1286548 TI - Maternal postprandial blood glucose levels influence infant birth weight in diabetic pregnancy. AB - Relationships between maternal glycaemia and neonatal birth weight were studied prospectively in 14 tightly controlled pregnant women with pre-existing type 1 diabetes mellitus. Maternal glycaemia throughout pregnancy was determined from daily self blood glucose (BG) monitoring with memory meters and fortnightly fructosamine (Fr) and glycated haemoglobin (HbA1) measurements. Mean non-fasting BG and mean HbA1 throughout pregnancy correlated strongly (Spearman rank) with birth weight (0.64 and 0.73 respectively), as did mean second trimester non fasting BG (0.54), HbA1 (0.7) and Fr (0.64) and mean third trimester HbA1 (0.65), whereas mean fasting BG showed no significant correlations with birth weight at any age of pregnancy. The disparity between the strong correlation of non fasting BG with birth weight and the poor correlation of fasting BG suggests that postprandial as opposed to basal glycaemia significantly influences foetal growth and neonatal size. PMID- 1286549 TI - Significance of 3HOH generation from D-[2-3H]glucose. AB - The significance of 3HOH generation by cells exposed to D-[2-3H]glucose is reevaluated. It is proposed that such a metabolic variable, rather than being taken as an index of D-glucose phosphorylation, may provide information on the extent of D-glucose 6-phosphate and D-fructose 6-phosphate interconversion in the reaction catalyzed by phosphoglucoisomerase. In order to reach such an information, the total production of 3HOH from D-[2-3H]glucose needs to be corrected for that attributable to either the catabolism of D-[1-3H]fructose 1,6 bisphosphate or the circulation of D-[2-3H]glucose 6-phosphate in the pentose phosphate pathway. A method is introduced which allows for such a correction. PMID- 1286550 TI - Antipyretic therapy in the febrile child. AB - General principles of thermoregulation, the pathophysiology of fever, controversies concerning the use of antipyretic therapy, and nonpharmacologic and pharmacologic treatments commonly used for antipyresis in the pediatric population are reviewed. Several arguments can be made for not ameliorating the febrile response. Fever is an important diagnostic and prognostic clinical sign that may have beneficial effects for the host. In addition, body temperatures of < or = 41 degrees C (105.8 degrees F) are relatively harmless. Reasons for treating fever include patient discomfort, the potential for adverse sequelae, the possibility of seizures, and the possibility that fever could affect the pharmacokinetic profiles of drugs. Nonpharmacologic treatment for fever includes environmental measures to enhance dissipation of body heat and sponging. Aspirin and acetaminophen are the agents used most frequently for antipyresis in pediatric patients. However, aspirin use in children with a viral illness has been associated with development of Reye's syndrome. As a result, its use in children has declined in the United States. Acetaminophen is relatively free of adverse effects and is considered first-line pharmacologic antipyresis therapy. Ibuprofen suspension should be considered as second-line antipyretic therapy. Combination therapy with acetaminophen and aspirin may be considered if the patient fails to respond to other nonpharmacologic and pharmacologic therapies; however, combination therapy may result in increased risk of drug toxicity, increased probability of adverse reactions, and increased risk of intoxication. Aspirin, acetaminophen, and ibuprofen are equally effective for antipyresis in pediatric patients. However, because acetaminophen is the safest medication, it is currently the therapy of choice. PMID- 1286551 TI - Toxicity of rapidly infused concentrated intravenous immune globulin. PMID- 1286552 TI - Pharmacokinetics of ondansetron in patients receiving cisplatin therapy. PMID- 1286553 TI - Removal of ethosuximide and phenobarbital by peritoneal dialysis in a child. PMID- 1286554 TI - Criteria for use of theophylline (aminophylline) in inpatients and outpatients with pulmonary disease. PMID- 1286555 TI - Cefpodoxime marketing approved by FDA. PMID- 1286556 TI - Evolution in indications for blood component transfusion. AB - Indications for blood components are changing but continue to be based on a combination of clinical assessment and laboratory data. In the perioperative setting, some decisions must be made before laboratory data are available. To prevent the inappropriate usage of blood components, prophylactic or expectant treatment should be limited. In red cell transfusion, physiologic indices of oxygen utilization may soon supplement hemoglobin/hematocrit levels in clinical decision making. Less progress has been made in transfusion for hemostasis. Well designed clinical studies are needed to answer remaining questions; in the interim, nationally accepted guidelines are available to assist clinicians in their decisions. PMID- 1286557 TI - Donor screening. AB - The primary goals of donor screening are to protect the recipient and safeguard the donor. These goals are accomplished through a variety of techniques, the most important of which is the donor medical history interview. This article reviews all elements of predonation donor screening, including donor education, the medical history interview, and the confidential unit exclusion procedure. Specific guidelines, including a proposed national uniform donor medical history questionnaire, are provided for all aspects of donor screening. PMID- 1286558 TI - Safety in transfusion practices. Red cell compatibility testing issues. AB - Pretransfusion compatibility testing, if performed properly, helps to maximize the effectiveness of transfusion therapy and to minimize the risk of hemolytic transfusion reactions. Each laboratory should select the procedures and protocols that are best suited to meet their patient care and institutional needs. Quality assessment monitoring of the elements of compatibility testing helps to ensure a high level of safety for patients receiving transfusion therapy. PMID- 1286559 TI - Safety in transfusion practices. Preventing infectious complications. AB - The benefits of transfusion therapy must always be weighed against the unavoidable chance of an infectious complication. Strategies to minimize the infectious risks inherent in the use of human blood and blood components can be categorized under four general headings: donor selection, testing, appropriate use, and follow-up and reporting of complications. The application of these strategies in the context of their role in the prevention of some of the infectious complications of transfusion therapy is discussed in this article. PMID- 1286560 TI - Leukocyte-reduced blood components in transfusion medicine. Current indications and prospects for the future. AB - Transfusion medicine is a rapidly evolving specialty, and efforts are ongoing to improve the safety and quality of blood component therapy. Leukocytes are known to be the cause of numerous adverse effects of transfusion therapy, and their removal from red cells and platelet components may be desirable in a variety of clinical settings. The various complications of transfusion that can be attributed to contaminating leukocytes and the benefits of leukocyte depletion are addressed in this article. Laboratory as well as clinical data are summarized. PMID- 1286561 TI - Immunosuppressive effects of blood transfusion. AB - Various in vitro studies, animal models, and retrospective investigations suggest that blood transfusion modulates the immune system. Not all studies, however, support this trend. This article provides a balanced presentation of the issues surrounding the concept of the immunosuppressive effects of blood transfusion. PMID- 1286562 TI - Special issues in transfusion medicine. AB - This article reviews four controversial aspects of transfusion practices: the clinical circumstances, survival, and complications of massive transfusion; specific problems related to neonatal transfusion practices and the surgical support of the small child, including the appropriate age for red cells to be transfused, cytomegalovirus transmission, and the reduction in homologous donor exposures; the clinical presentation, incidence, and prevention of transfusion associated graft-versus-host disease; and the biochemistry, function, genetics, and clinical indication for replacement therapy of antithrombin III. PMID- 1286563 TI - New testing approaches in transfusion medicine. AB - A revolution has occurred in the availability of molecular diagnostic technology in the last decade. We are just now beginning to bridge the gap between research and the availability of rapidly licensed clinical assays. Many of these new technologies will be useful in the general practice of transfusion medicine. Some of these techniques may be discarded as impractical. However, many of these methods should prove to be useful in clinical transfusion research and diagnosis. PMID- 1286564 TI - Limiting homologous blood exposure. AB - Successful limitation of homologous blood transfusion may necessitate multiple strategies and advance planning. Preoperative and intraoperative autologous blood collection may have to be supplemented with hemostatic pharmacologic agents. The use of cytokines is increasing. More efficient use of directed donors can have an important role in blood use. As these expensive and time-consuming techniques become available, a major challenge will be to determine which patients may benefit from or really need them. PMID- 1286565 TI - Inactivation of microbial contaminants of blood components. AB - Despite the low risk of transfusion-transmitted infection currently present in the blood supply, processes to inactivate contaminating viruses and bacteria may improve the safety of transfusion even further. A variety of techniques, using both physical and chemical processes, are being explored. Particularly promising is adaptation of the solvent/detergent technique (already in use for plasma derivatives) to plasma for transfusion. Inactivation of viruses in cellular components may require a combination of techniques, possibly including leukocyte depletion filtration, photoactive compounds, and subsequent washing. Concerns about potential toxicity of the agents employed and retention of component efficacy after treatment and storage remain unresolved, however. PMID- 1286566 TI - Redefining and expanding quality assurance. AB - To meet the current standards of excellence necessary for blood establishments, we have learned from industry that a movement toward organization-wide quality assurance/total quality management must be made. Everyone in the organization must accept responsibility for participating in providing the highest quality products and services. Quality must be built into processes and design systems to support these quality processes. Quality assurance has been redefined to include a quality planning function described as the most effective way of designing quality into processes. A formalized quality planning process must be part of quality assurance. Continuous quality improvement has been identified as the strategy every blood establishment must support while striving for error-free processing as the long-term objective. The auditing process has been realigned to support and facilitate this same objective. Implementing organization-wide quality assurance/total quality management is one proven plan for guaranteeing the quality of the 20 million products that are transfused into 4 million patients each year and for moving toward the new order. PMID- 1286567 TI - Legal issues in transfusion medicine. Is blood banking a medical profession? AB - In legislation concerning the transfusion of AIDS, the issue of whether blood banking is a profession has become extremely important. The status of blood banking determines how blood center actions will be judged and what liability rules will be applied. The issue was recently hotly argued in the high courts of Colorado and Florida. The courts' decisions impact not only on the outcome of other lawsuits regarding the transfusion of AIDS against blood banks, but also on the way blood bank practices will be made in the future. PMID- 1286568 TI - Regulatory and legislative issues in transfusion medicine. AB - The nation's blood supply is safer than ever following the implementation of more restrictive donor screening and additional tests for infectious agents. As a result of the AIDS crisis, however, there is a heightened awareness that blood transfusion is not an entirely benign therapy. As blood banking practices continue to undergo close scrutiny by members of Congress, regulators, and the American public, blood banks and transfusion services are striving to communicate effectively their efforts to ensure the provision of quality blood components and services. PMID- 1286569 TI - The fourth dimension. Management of the postmodern clinical laboratory. AB - The clinical laboratory has undergone historic changes over the past decade. The Clinical Laboratory Improvement Amendments of 1988 are the regulatory acknowledgement of the technological revolution that has occurred. Challenged to meet increasingly diverse medical needs while facing cost restraints, managerial leadership will replace technical leadership in the clinical laboratory. Ignored for half a century by most American industries, total quality management has been invoked as the embodiment of systems engineering and group decision making in the postmodern clinical laboratory. The matrix organization, workload recording, and productivity measuring are cost-effective applications of total quality management in the clinical laboratory. PMID- 1286570 TI - Changes in serum erythropoietin levels during chemotherapy for lung cancer. AB - Serial serum erythropoietin (EPO) levels were measured in 12 adult lung cancer patients during cancer chemotherapy. In major cases, EPO levels increased significantly after chemotherapy while the hemoglobin (Hb) remained at initial levels. EPO fell gradually or rapidly to initial levels after a peak, although the patients were anemic. The increase of EPO levels was linearly related to the decrease in Hb (y = 17.48x + 1.003). The mechanism of the rapid increase of EPO is not simply explained by anemia, but might be related to new synthesis, corresponding to depressed bone marrow. PMID- 1286571 TI - Simple method for measuring the antibiotic concentration required to kill adherent bacteria. AB - A simple method was developed for measuring the antibiotic susceptibility of bacteria adherent to plastic surfaces. Staphylococcus aureus cells adhered to the bottom of a 96-well plastic tissue culture plate were incubated in serially diluted antibiotic solutions. After a 24-hour-incubation the solutions were removed, and fresh medium without antibiotics was added to each well. The viability of the cells was judged by their growth after a further 24-hour incubation. The antibiotic concentration required to kill adherent bacteria was far higher than that required for planktonic cells, although we used bactericidal drugs; beta-lactam, quinolone, and aminoglycoside antibiotics. The tolerance demonstrated by adherent cells is likely to play a role in the difficulties encountered in the chemotherapy of biofilm infections. PMID- 1286572 TI - Beta-lactamase expression and cross-resistance to beta-lactam antibiotics in a nosocomial population of Enterobacter. AB - This study sought to quantitatively describe the spectrum of constitutive and inducible beta-lactamase activity present in a tertiary care center's population of Enterobacter species. beta-Lactamase activity in the absence and presence of 2 recognized beta-lactamase-inducing antibiotics, cefoxitin and imipenem, was measured. The Enterobacter cloacae (n = 35) population was strikingly bimodal, expressing 'all-or-none' cross-resistance to beta-lactams (except imipenem) corresponding to the baseline level of beta-lactamase expression. E. aerogenes (n = 14) displayed a less dichotomous pattern of resistance, and MICs of beta-lactam antibiotics were less strongly related to the magnitude of enzyme activity. We conclude that our nosocomial population of E. cloacae, like strains rendered resistant to beta-lactams in vitro, is largely dependent upon beta-lactamase as a mechanism of this resistance. Furthermore, we document the presence of a large subpopulation of beta-lactam-susceptible isolates possessing inducible beta lactamase and therefore subject to selection for enzyme derepression. PMID- 1286573 TI - In vitro activity of amphotericin B, hamycin and their novel water-soluble compounds against pathogenic yeasts. AB - Twenty-eight pathogenic isolates, 4 each of Candida albicans, C. lusitaniae, C. parapsilosis, Cryptococcus neoformans, Torulopsis glabrata and Trichosporon beigelii were tested for their in vitro sensitivity to amphotericin B (AmB), hamycin (HA) and their novel water-soluble compounds, namely JAI-AmB (oral and injectable; patents pending) and JAI-HA (Jaimycin Inc., Walnut Creek, Calif., USA), using a standard double-dilution broth (1 ml/tube) procedure. The 2 novel compounds, namely JAI-AmB and JAI-HA, contain one twenty-fifth (w/w) of the AmB and HA, respectively. Results showed that the minimal inhibitory concentrations (MICs) of AmB for all species, except C. lusitaniae and Tr. beigelii (3.125-6.25 micrograms/ml), were 0.195-1.56 micrograms/ml. The values of JAI-AmB (oral) for C. albicans, C. parapsilosis, Cr. neoformans and To. glabrata ranged from 0.78 to 25 micrograms/ml. The MICs of JAI-AmB (oral) for the other yeasts were 100 micrograms/ml. All of the yeasts yielded higher MICs (3.125-100 micrograms/ml) against JAI-AmB (injectable) than the JAI-AmB (oral) preparation. Except for C. parapsilosis (MICs 25-100 micrograms/ml), all of the other species showed greater sensitivity to the parent HA (0.195-100 micrograms/ml) than AmB. The values for JAI-HA ranged from 0.195 to 100 micrograms/ml for all isolates, except C. tropicalis (100 micrograms/ml). Based on our in vitro findings, in vivo efficacies of JAI-AmB and JAI-HA should be carried out. PMID- 1286574 TI - Incidence of beta-lactamase production among out patient clinical isolates in Middle Eastern countries and their antibiotic susceptibilities. Middle Eastern Study Group. AB - In a multicenter survey in seven Middle Eastern countries, 1,827 clinical isolates from patients with community-acquired infections (outpatients) were examined for both production of beta-lactamase and their susceptibility to commonly prescribed antibiotics. Of these isolates, 63% were gram-negative and 37% were gram-positive organisms. beta-lactamase was produced by 65% of all isolates, representing 61 and 75% of gram-negative and gram-positive organisms, respectively. Using standardized disk susceptibility testing, high rates of resistance were observed among gram-negative and gram-positive organisms, respectively, for penicillin (86 and 75%), ampicillin (67 and 66%) and amoxicillin (58 and 52%). Resistance to tetracycline and co-trimoxazole were also seen, but to a lesser degree. Susceptibility of these organisms towards the cephalosporins cepharadine, cephalexin and cefadroxil ranged from 30 to 70%, which appears to correlate fairly closely with the prevalence of beta-lactamase production. Cefuroxime inhibited about 94 and 79% of gram-positive and gram negative organisms, respectively, regardless of the production of beta-lactamase. These data are valuable since antibiotic therapy is usually instituted on a best guess principle against the most likely potential pathogens. PMID- 1286575 TI - In vitro activity of meropenem and other agents against oral bacteria. AB - The susceptibility of 106 oral bacteria to meropenem, a new carbapenem antimicrobial, penicillin V, tetracycline and metronidazole was assessed by an agar dilution method. Meropenem was the most effective of the antimicrobials, with all strains tested being inhibited at < or = 1 mg/l. A number of strains were resistant to penicillin V, particularly Bacteroides gracilis, and tetracycline resistance was widespread amongst the streptococci tested. Metronidazole was extremely effective against obligate anaerobes. The results of this study suggest that meropenem has potential for use in the treatment of serious head and neck infections. PMID- 1286576 TI - Studies on the antibiotic transfer into the bile of canines with different bile duct pressures. AB - There have been many studies on the transport of antibiotics into the bile; however, these studies have not taken the bile duct pressure into consideration. The bile duct pressure of the patient with acute obstructive cholangitis is high, and after drainage of the bile, the pressure is not always decreased to the normal range. We studied the effects of the bile duct pressure on the antibiotic (flomoxef sodium) transfer into the bile using beagles after creating the model of acute obstructive cholangitis. Our results showed that sufficient bile flow after drainage is important for the antibiotic transport, and, moreover, the bile acid concentration which may be related to the bilirubin concentration is also highly considerable. PMID- 1286577 TI - Experimental evaluation of preventive and therapeutic potentials of lysozyme. AB - Therapeutic efficacy and preventive role of egg white lysozyme was evaluated in three types of murine ascitic tumours, namely sarcoma 180, Ehrlich's carcinoma, and Dalton's lymphoma. Lysozyme treatment produced regression of tumour growth and improved the life expectancy of the host. Growth of tumour cells treated in vitro with lysozyme prior to transplantation was also affected. In addition, lysozyme was found to have a preventive effect when administered to normal mice. The antitumour activity, therapeutic and preventive, of lysozyme seems to be due to its action on the tumour cell surface as well as on the host-mediated immune response. PMID- 1286578 TI - Effect of tetrahydrouridine on metabolism and transport of 1-beta-D arabinofuranosylcytosine in human cells. AB - Deamination of cytosine arabinoside (ara-C) by cytidine deaminase is the main mode of inactivation of this drug which can be responsible for ara-C resistance. The present study was undertaken to determine the effect of tetrahydrouridine (THU; a potent inhibitor of cytidine deaminase) on ara-C transport and metabolism in human cells. A rapid transport of ara-C into freshly isolated hepatocytes and an increased intracellular accumulation of the unchanged drug were observed in the presence of 50 micrograms/ml THU. THU inhibited the intracellular deamination of ara-C by 80% and slowed elimination of the compound extracellularly. The intracellular ara-C concentrations achieved after incubation with 1 micrograms/ml ara-C plus 50 micrograms/ml THU are similar to those attained with ara-C (10 micrograms/ml) alone. Treatment of leukemic K562 cells with the combination of THU (50 micrograms/ml) and ara-C (1 micrograms/ml) led to an augmentation of intracellular ara-C triphosphate formation up to twofold. PMID- 1286579 TI - Two cases of disseminated toxocariasis in compromised hosts successfully treated with mebendazole. AB - Two cases of disseminated (hepatosplenic, pulmonary and in 1 case also cerebral) toxocariasis in compromised hosts-1 with malignancy (mycosis fungoides) and 1 on chronic corticosteroid treatment due to autoimmune disease--are reported. Besides fungi, also other unusual pathogens (of parasitic origin), especially in cancer, shall be considered. PMID- 1286580 TI - [A comparison between nasotracheal and orotracheal intubation in treating chronic obstructive pulmonary disease complicated by respiratory failure]. AB - Endotracheal intubation and mechanical ventilation were given to 100 COPD patients complicated by respiratory failure from Dec. 1977 to May 1990. Among them 42 were intubated through mouth. The tubes were kept from 1 to 6 days. In only 8 cases (19.0%) the tubes could be withdrawn according to the criterion, and 25 patients (59.0%) were tracheostomized. Nasotracheal intubation were given to 58 patients. The tubes were kept from 1 to 220 days and could be withdrawn in 39 cases (81.0%), with an incidence higher than that in patients intubated orotracheally (P < 0.01). Tracheostomy mas given to 6 patients intubated nasotracheally (10.3%), being fewer than in patients intubated through mouth (P < 0.01). Although the tubes have been kept for longer time, the duration of hospitalization was not prolonged. PMID- 1286581 TI - [Perfusion lung scan in unexplained pulmonary hypertension]. AB - Thirty-two patients were diagnosed as unexplained pulmonary hypertension by clinical history, physical examination, hemodynamics, pulmonary angiography and perfusion lung scanning. The findings of pulmonary scans in twenty patients (62.5%) showed patchy heterogeneous perfusion defects, which suggested chronic silent pulmonary thromboembolism (CSPT) and in twelve cases (37.5%) demonstrated normal or equally diffuse radionuclide scattering due to primary pulmonary hypertension (PPH). This result corresponded with the pathological data in some of the relevant references. Pulmonary perfusion scan is a noninvasive, safe and simple procedure for determining whether CSPT or PPH is the causative factor in patients with unexplained pulmonary hypertension. PMID- 1286582 TI - [Nosocomial pneumonia: a report of 372 cases]. AB - Three hundred seventy-two cases of hospital-acquired pneumonia occurring during a 4-year period were reviewed. It was found that the annual incidence of the pneumonia was 1.44% which ranked first in the incidence of nosocomial infections at this institution. Most of the patients had suffered from primary severe underlying diseases with immunosuppression of different degrees. A variety of factors such as antibiotic and steroid therapy, operation, intensive care, endotracheal intubation, tracheostomy, chemotherapy and radiotherapy predisposed to the acquisition of this pneumonia. Most frequent etiologic agents for hospital acquired pneumonia were Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. The overall mortality rate was 25.3%. However, deaths associated with Pseudomonas aeruginosa and Staphylococcus aureus are particularly high, with rates of 70.6% and 66.7% respectively. The incidence, mortality, pathogenesis, diagnosis, treatment and prevention of the disorder were discussed briefly. PMID- 1286583 TI - [Correlation among electrocardiogram, important risk factors of coronary artery diseases and coronary lesion in patients with chest pain]. AB - Clinical and angiographic data from 103 patients with chest pain were evaluated to determine their correlation with ST-T abnormality in resting electrocardiogram. Univariate analysis suggested that male sex, hypertension, old myocardial infarction, severe coronary lesion, multiple vessel lesion and left ventricular wall motion abnormality significantly increase the likelihood of ST-T abnormality. Multivariate analysis suggested that male sex, hypertension and left ventricular wall motion abnormality were significant independent predictors of abnormal ST-T. It is essential to improve the electrocardiographic accuracy of diagnosing CAD so as to help clinical doctors in preventing and treating this disease. PMID- 1286584 TI - [Tumor necrosis factor and interleukin 6 in hepatitis C virus infection]. AB - Tumor necrosis factor (TNF) was determined with ELISA in 72 patients with hepatitis C and hepatitis B virus infections. Interleukin 6 (IL-6) was determined at the same time. TNF and IL-6 were significantly increased in patients with hepatitis C virus infections when compared with normal subjects and hepatitis B patients. There was a significant positive correlation between TNF and IL-6. It is suggested that increased TNF and IL-6 may play an important role in pathogenesis of hepatitis C virus infection. PMID- 1286585 TI - [Detection of anti-dsDNA-F(AB')2 antibody and evaluation of its clinical significance]. AB - Purified anti-dsDNA antibody was obtained from the serum of patients with systemic lupus erythematosus by affinity-column chromatography. Anti-dsDNA F(ab')2 fragment (idiotype) was prepared from digested anti-dsDNA antibody with pepsin. We have developed a sensitive and specific method for detection anti dsDNA-F(ab')2 antibody. Our result revealed that low titer of anti-dsDNA was observed in patients with active stage of systemic lupus erythematosus. PMID- 1286586 TI - [Effects of various recombinant human hematopoietic growth factors on proliferation of blast cells in acute myeloid leukemia in vitro]. AB - In vitro proliferative response of the blast cells from 21 AML patients to hematopoietic growth factors (IL-3, GM-CSF, G-CSF and MCSF) was investigated. Proliferation of AML cells in the majority of cases was induced or promoted by one or more CSFs, among which the stimulation of IL-3 was the most effective. Spontaneous proliferation of the blast cells was also observed in half of the cases and could be inhibited as well as promoted by some CSFs. It is suggested that in vitro proliferation of AML cells varies from patient to patient and that CSF plays important roles in leukemogenesis. PMID- 1286587 TI - [Associations between plasma insulin and high blood pressure]. AB - We studied the relationship between plasma insulin level and hypertension in 510 cases with normal glucose tolerance and impaired glucose tolerance. In nonobese group (BMI < 25kg/m2), plasma insulin was higher in those with hypertension than those with normal blood pressure (P < 0.0001). There was no correlation between diastole blood pressure and plasma insulin; multiple regression analysis showed that fasting plasma insulin was significantly associated with systolic blood pressure after controlling age, BMI and plasma glucose level (beta = 0.27, P = 0.0078). The result suggested that age, BMI and plasma insulin level were independent risk factors of hypertension. In obese group (BMI > 25kg/m2), blood pressure was significantly associated with age and BMI, there was no association between blood pressure and plasma insulin level. PMID- 1286588 TI - [Oxygen-independent microbicidal mechanisms of neutrophils]. PMID- 1286589 TI - [Long-term effects of intracerebral implantation of adrenal medulla in the treatment of parkinsonism]. AB - 24 patients with parkinsonism received intracerebral autotransplantation of adrenal. Follow-up for 1-4 years showed that the long-term effectiveness was 70.8%, and the substantial effectiveness 41.7%. The patients with no improvement or deterioration after some improvement comprised 20.8%. The operative mortality rate was 8.3%. Possible factors influencing the effectiveness were analysed, and how to improve the survival rate of the implanted chromaffin cells was also discussed. PMID- 1286591 TI - [Transaxillary approach first rib resection for thoracic outlet syndrome]. AB - From 1981 to 1991, 26 patients with thoracic outlet syndrome were treated by transaxillary first rib resection. Investigation of its indications, modes and results showed that this is one of the ideal methods of treatment for thoracic outlet syndrome. PMID- 1286590 TI - [Congenital absence of vein valves of the lower extremities]. AB - Sixteen patients with congenital absence of venous valves in the deep veins of 18 lower limbs are reported. The disease limbs characterized by venous hypertension is frequently seen in teen-agers. Venographically, no valve is to be found in the deep venous system. Conservative treatment may be tried in those without pigmentation and ulcer formation in the goiter area. However, valvular reconstructive operation of the deep veins is the effective method of treatment. PMID- 1286592 TI - [Successful replantation of circularly severed palm and multiply severed fingers. A case report]. AB - Replantation of a circularly severed palm, partially severed middle finger and completely severed ring and small fingers was done successfully in one patient. Two palmar arteries, 5 digital arteries, 3 dorsal palmar veins, 9 dorsal digital veins were anastomosed. Vein transplantation was carried out to repair the ulnar digital artery defect of the middle finger. Severe swelling after arterial thrombosis was noted on the 7th day and was eliminated by the use of urokinase. All the replanted parts survived with good functional results. Precise anastomosis, prevention and treatment of thrombosis, early exercises were essential to the survival of fingers and functional recovery of hand. PMID- 1286593 TI - [Cavernomas of the central nervous system]. AB - 18 cases of pathological cavernoma of the central nervous system were reported. The took 11.25 per cent of verified vascular malformations in our department in the same period. 15 cases located intracranially, and 3 cases were within the vertebral canal. Repeated small amount hemorrhages in the lesions were the major cause of the clinical symptoms of these patients. MRI was the most reliable method for making a correct diagnosis of cavernomas before operation. Cavernomas usually had clear border and surrounded with gliotic tissues, so that extirpation of tumor with microsurgical technique was the best choice. PMID- 1286594 TI - [A study on origin of the hyperplastic synovial lining cells in rheumatoid arthritis]. AB - The one of striking microscopic feature is synovium hyperplasia in rheumatoid arthritis. The origin of the hyperplastic synovial lining cells in RA remains unsettled. Two marked monoclonal antibodies and two marked antisera are used to run the immunohistochemical study. Our finding revealed that synovial lining cells bear marks for blood monocytes. It is suggested that the increased synovial lining cells population appear to derive from bone marrow. Besides, the results of immunoelectron microscopy showed that synovial lining cells of type A and type C express HLA-DR antigen. HLA positive dendritic cells are distinctly more frequently seen in RA synovium than in that of osteoarthritis. PMID- 1286595 TI - [Effect of glutamine and glutamine-dipeptide enriched amino acid solution on rat small bowel mucosa regeneration]. AB - To mine the effects of glutamine and it's dipeptide enriched nutrition solution on the gastro-intestinal structure and protein metabolism, 40 male Wistar rats were studied for 8 days. The rats were randomly divided into four groups: sham operation group, standard amino acid solution group, glutamine enriched group and glutamine dipeptide enriched group. Observation parameters were: weight change; serum AA profile analysis; computerized morphometric analysis of mucosa thickness and villus height; total nitrogen balance; and liver, kidney functional results. The data were managed by multiple sample comparison methods (ANOVA of Statview 512 software) on Macintosh PC. Significant level was put on P < 0.05. The results showed that significant differences of body weight, serum glutamine level, nitrogen balance, intestinal mucosa thickness and villus height were found between the control and study groups. No significant difference in liver and kidney function was found. Gln-Ala dipeptide had same effects as free glutamine did. PMID- 1286596 TI - [A clinical investigation of rHuIFN alpha-1 in the treatment of herpes simplex virus keratitis]. AB - A double blind clinical investigation on the treatment of 100 cases of HSV keratitis with rHuIFN alpha-1 and acyclovir instillations was carried out in 8 institutions in Beijing and elsewhere. Both eyedrops proved about equally effective with cure rates of 88.1% and 82.9% respectively. Until recently, 128 cumulative cases of various types of HSV keratitis treated with rHuIFN alpha-1 demonstrated a cure rate of 82.0%, indicating that topical rHuIFN alpha-1 was an effective nonspecific remedy for HSV keratitis. PMID- 1286598 TI - [A preliminary report of epikeratophakia for the treatment of myopia]. AB - Since 1987, 9 cases of high myopia were treated by epikeratophakia with concave corneal lenses shaped by a rapid method on a self-made cryolathe. After the surgery, all patients showed reduced degrees of myopia and astigmatism, with marked improvement in uncorrected visual acuity. The corrected visual acuity was the same as preoperative in 3 cases and improved in 6 cases. No serious complications occurred. PMID- 1286597 TI - [Treatment of severe Mooren's ulcer with cyclosporin A eyedrops]. AB - 16 patients (21 eyes) with severe progressive Mooren's ulcer unresponsive to medical or surgical therapy were treated with 0.5% cyclosporin A (CsA) eyedrops. 15 eyes showed remarkable amelioration within 12 days, and 11 eyes completely healed without side effects in an average 1.3 months. The total effective rate was 83.3%, with no recurrence in a follow-up of 12-19 months. Whole-blood levels of CsA were determined by high pressure liquid chromatography to average 28.95 ng/ml in 7 random patients. Autoimmunity was believed to be an important factor in the pathogenesis of Mooren's ulcer, and the efficacy of topical CsA was attributable to the local depression of ocular immunopathological reactions. PMID- 1286599 TI - [Evaluation of penetrating keratoplasty for the treatment of keratoconus]. AB - 22 cases (26 eyes) of keratoconus were performed penetrating keratoplasty and followed up 0.5-5 years. The disease was effectively controlled. The rate of graft transparency was 100%, and the immune rejection rate was 7.7%. Corrected vision was 0.4 or better in 23 cases after the operation. The authors regard keratoplasty the best choice for treatment of keratoconus. PMID- 1286600 TI - [An immunohistochemical study of Langerhan's cells (LC), T-cells and the HLA antigen in human cornea]. AB - The distribution of Langerhan's cells (LC), T-cell subsets, and HLA system in 12 normal and 7 morbid corneas, including 4 of suppurative corneal ulcer and 3 of uveogenic endophthalmitis, were investigated with monoclonal antibodies. The results revealed that a small amount of LC and T-cell subsets were present in the limbal region of normal corneas, while large numbers of LC and OKT4+ were observed in the corneas of suppurative ulcer. HLA-ABC antigens were expressed on the epithelial cells and keratocytes of the normal corneas, while the HLA-DR antigens were expressed on the surface of LC at the limbus. PMID- 1286601 TI - [Recovery of corneal sensitivity following keratoplasty and corneal diseases]. AB - Corneal sensitivity (CS) was tested in 201 eyes with clear plastic grafts and in 193 eyes with corneal diseases, using the Cochet-Bonnet Aesthesiometer. After keratoplasty, the CS returned to normal in 40.0% and 50.0% of the eyes with non HSK in 5-6 years and 7-22 years respectively, while only 17.2% of the eyes with HSK showed normal CS in 7-22 years postoperative. The corneas of HSK patients were markedly hypoesthetic all over, whereas in non-HSK patients, the corneal hypoesthesia involved only the morbid area. The examination of CS is useful in the diagnosis of corneal diseases and evaluation of nerve regeneration after keratoplasty. PMID- 1286602 TI - [The clinical significance of following up the differential light threshold in glaucoma]. AB - The correlation of the differential light threshold changes in the Bjerrum area to the glaucomatous visual field defects that followed was studied prospectively by the Humphrey Field Analyzer. Of 42 early glaucomatous eyes without field defects, 24 developed reproducible glaucomatous field defects in 2.5 years of follow-up. The agreement in location between the field defects and the meridian of highest light threshold elevation was remarkable (87.0%), and a mean 5 dB decline in local light sensitivity predicted ensuing field defect development. Thus, the discovery of glaucomatous field defects with automated Humphrey perimetry could be 1-2 years earlier than with Goldmann perimetry. PMID- 1286603 TI - [The exfoliation or pseudo-exfoliation syndrome]. AB - The exfoliation or pseudo-exfoliation syndrome (PE) is very rare in China. The clinical and histopathologic features in 13 patients were that the loss of pigment at the pupillary ruff and dense pigmentation on the trabecular meshwork were early signs easily overlooked, and the dandruff-like particles at the pupillary margin and greyish white ring at the anterior periphery of the lens were typical findings. Histopathologic study demonstrated that the PAS-positive amorphous material under light microscopy were fibrils in structure and accumulated at various sites in the anterior segment of the eye. PMID- 1286605 TI - [Family investigation and clinical genetic analysis of a large pedigree with congenital stationary night blindness]. AB - A large pedigree of congenital stationary night blindness (CSNB) was investigated by both the family method and the family history method, and the diagnosis was confirmed by dark adaptation and full-field electroretinogram tests. There were 57 affected members of 7 successive generations in the pedigree which showed typical autosomal dominant inheritance with a complete gene penetrance. Based on this study and other sources, the genetic aspect and the clinical manifestations of CSNB, especially the characteristics of dark adaptation and electroretinogram, were discussed. PMID- 1286604 TI - [Clinical applications of MRI in ophthalmology]. AB - Magnetic resonance imaging (MRI) of the normal eyeball and orbital tissues is introduced, along with the MRI manifestations in 39 patients comprising 6 cases of intraocular and 29 cases of intraorbital disorders, and 4 cases of vascular diseases. The advantages and limitations of MRI in ophthalmology are discussed. It appears that MRI is more sensitive than ultrasonic B-scan or CT. PMID- 1286606 TI - [The effect of dosage on oral fluorescein angiography of the fundus]. AB - 105 patients were orally given fluorescein of different dosage and concentration for fundus angiography. The results indicated that the dosage of 30mg/kg at 2% concentration produced more distinct angiograms. PMID- 1286607 TI - [A clinical study of vertical saccadic eye movements]. AB - The authors studied the vertical saccadic movements of 12 patients with vertical paretic strabismus (< 6 degrees) by Scott's method, comparing the saccade of the paretic muscle with that of its antagonist. The results showed that the former was reduced in amplitude by 15%-50%, averaging 31.5%, and improved to 0%-25%, averaging 8.1%, after operations. The authors proposed that a difference of saccadic amplitude over 15% between a muscle and its antagonist indicated presence of muscle paresis. Besides, the methods of assessing saccadic movements were discussed. PMID- 1286608 TI - [An experimental study of gentamycin delivery into cornea and aqueous humor from the collagen corneal shield]. AB - Collagen corneal shields immersed in 13.33 mg/ml gentamycin solution for 5 minutes were placed in rabbit eyes and the gentamycin concentrations in the cornea and aqueous humor were determined with radioimmunoassay. The results were compared with those achieved by soft contact lens, subconjunctival injection, and frequent instillations. It was found that (1) 1 and 3 hours after application, the collagen corneal shield produced significantly higher concentration of gentamycin in the aqueous than did the other methods, and in the cornea than did the contact lens or instillations; and (2) 6 hours after application, the antibiotic level in the cornea dropped lower than that by subconjunctival injection, but still 15-30 times higher than the bactericidal concentration. PMID- 1286609 TI - Responses of the ticks Amblyomma hebraeum and A. variegatum to known or potential components of the aggregation-attachment pheromone. III. Aggregation. AB - Ten known or potential components of the aggregation-attachment pheromone (AAP) of the ticks Amblyomma hebraeum and A. variegatum, as well as mixtures of these components, extracts of prefed males and live prefed males, were tested as aggregation stimulants. In field assays, laboratory-reared unfed male and female ticks were released 20 cm downwind of CO2/pheromone release sites; the numbers of ticks that aggregated at the release sites were recorded after 30 min. In A. variegatum, aggregation was induced by methyl salicylate, o-nitrophenol, 2,6 dichlorophenol, phenylacetaldehyde and some mixtures containing these compounds; a strong aggregation response was induced by an extract of five prefed males A. variegatum and a weak response was induced by an extract of 50 prefed males of A. hebraeum. In A. hebraeum, aggregation was induced by phenylacetaldehyde, mixtures of compounds that included phenylacetaldehyde, extracts of 50 prefed males of A. hebraeum or A. variegatum and 50 live prefed males of A. hebraeum. In A. variegatum, aggregation was inhibited if compounds that do not occur naturally in the AAP of the species were included in mixtures. In A. hebraeum, phenylacetaldehyde appeared to act as an arrestant for ticks that had been attracted to release sites by other compounds. PMID- 1286610 TI - Responses of the ticks Amblyomma hebraeum and A. variegatum to known or potential components of the aggregation-attachment pheromone. IV. Attachment stimulation of nymphs. AB - Ten known or potential components of the aggregation-attachment pheromone (AAP) of the ticks Amblyomma hebraeum and A. variegatum, as well as a mixture of these components and extracts of prefed males of the two species, were tested as attachment stimulants for nymphs. Unfed nymphs were confined in linen bags on the ears of rabbits that had been treated with the test compounds, mixture or extracts; the numbers attached were recorded after 24 h. In A. hebraeum, attachment was induced by four compounds (2-methyl propanoic acid, methyl salicylate, o-nitrophenol and salicylaldehyde), the mixture and extracts from both species. In A. variegatum, attachment was induced by three compounds (methyl salicylate, o-nitrophenol and salicylaldehyde), the mixture and extracts from both species. Methyl salicylate and o-nitrophenol are primary components of the AAP of both A. hebraeum and A. variegatum. 2-methyl propanoic acid is a species specific attachment stimulant for A. hebraeum. Salicylaldehyde, a phenolic compound, is not a naturally occurring AAP component. Nymphs of both species respond to fewer attachment stimulants than the adults and, as shown by their respective host ranges, are less dependent on the AAP in the regulation of attachment than the adults. PMID- 1286612 TI - Xenopus maternal RNAs from a dorsal animal blastomere induce a secondary axis in host embryos. AB - The initial steps of dorsal axis formation are controlled by localized maternal determinants in Drosophila, and a similar process has been proposed in Xenopus. The present study demonstrates that there are axis-inducing RNA molecules located in a specific dorsal midline, animal blastomere (D1.1) of the 16-cell-stage embryo. This blastomere, although in the animal hemisphere at cleavage stages, populates most of the dorsal lip of the blastopore, the region of Spemann's organizer, during gastrulation, and is the major progenitor for dorsal mesodermal tissues. Cytosol from this blastomere causes ventral cells to take a more dorsal fate. RNA from this blastomere induces a secondary axis when injected into ventral blastomeres and restores the dorsal axis in UV-irradiated embryos. In Xenopus, activin beta B, goosecoid and Xwnt-8 RNAs can ectopically induce a dorsal axis; however, none is a maternal transcript. Therefore, the D1.1 blastomere probably contains dorsal determinant(s) that are either maternal members of these gene families, or other presently unknown molecule(s). Regardless of the identity of the determinant(s), this study presents the first indication that Xenopus maternal RNAs in the dorsal animal hemisphere are able to organize the dorsal axis. PMID- 1286611 TI - The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. AB - Mutations in the gene ced-4 block almost all of the programmed cell deaths that normally occur during Caenorhabditis elegans development. We have cloned the ced 4 gene using a ced-4 mutation caused by the insertion of the transposon Tc4. When microinjected into a ced-4 animal, a 4.4 kb DNA fragment derived from the wild type strain and corresponding to the region of the Tc4 insertion in the mutant ced-4(n1416) rescues the Ced-4 mutant phenotype. The ced-4 gene encodes a 2.2 kb RNA transcript. This mRNA is expressed primarily during embryogenesis, when most programmed cell deaths occur. The Ced-4 protein, as deduced from cDNA and genomic DNA clones, is 549 amino acids in length. Two regions of the putative Ced-4 protein product show some similarity to known calcium-binding domains. PMID- 1286613 TI - Primary culture of single ectodermal precursors of Drosophila reveals a dorsoventral prepattern of intrinsic neurogenic and epidermogenic capabilities at the early gastrula stage. AB - We have analyzed the development in vitro of individual precursor cells from the presumptive truncal segmental ectoderm of the Drosophila embryo to study the intrinsic component in the determination of cell fate. For each cultured cell, the original position within as well as the developmental stage of the donor embryo were known. Cells removed from the ventral neurogenic region develop neural clones. Cells from the dorsal ectoderm and from the dorsalmost part of the ventral neurogenic ectoderm develop epidermal clones. These two classes of clones differ with respect to their division pattern, adhesiveness, cell morphologies and the expression of cell-specific markers. Mixed neural/epidermal clones were obtained from a fraction of precursors at almost all dorsoventral sites. We conclude that, at the onset of gastrulation, precursor cells of the truncal segmental ectoderm already have the capability to develop as either neuroblasts or epidermoblasts in the absence of further cell interactions. At the same time, positional cues distributed along the dorsoventral axis equip precursors with intrinsic preferences towards the neural or epidermal fate, thus defining a prepattern of high neurogenic preferences ventrally, and high epidermogenic preferences dorsally. It is likely that this prepattern is involved in defining the extent of the ventral neurogenic and dorsal epidermogenic regions of the ectoderm. The roles of intrinsic capabilities versus extrinsic influences in the regulation of the characteristic pattern of segregation of the two lineages are discussed. PMID- 1286614 TI - The presence of hepatocyte growth factor in the developing rat. AB - Hepatocyte growth factor (HGF), a heparin-binding polypeptide mitogen, stimulates DNA synthesis in adult rat and human hepatocytes and in several other cells of epithelial origin. Recently, it was determined that scatter factor (SF), a protein that has been shown to cause the dispersion and migration of epithelial cells in culture, is identical to HGF. Moreover, the receptor for HGF was identified as the product of the proto-oncogene, c-MET, a tyrosine kinase containing transmembrane protein. c-MET expression has been reported in a variety of adult and embryonic mouse tissues. Similarly, we and others have demonstrated that HGF is expressed in various adult rat and human tissues. In the present study, the tissue distribution of HGF during rat development was determined by immunohistochemistry using an HGF-specific polyclonal antiserum. Between day 12 and day 19, immunoreactivity for HGF was present in various locations such as hematopoietic cells, somites, squamous epithelium of the esophagus and skin, periventricular germinal matrix of the brain, bronchial epithelium, renal collecting tubules and chondrocytes. After day 19, HGF immunoreactivity was also present in the pancreas, submaxillary glands and neural tissues. In addition to immunolocalizing HGF in tissue sections, bioreactive and immunoreactive HGF was extracted and purified from rat fetuses. Other studies demonstrated the presence of HGF and c-MET mRNA in total fetal rat, and in fetal and neonatal rat liver. Addition of purified HGF to fetal and neonatal rat liver cultures enriched for hepatocytes stimulated DNA synthesis up to six-fold over controls. These findings strongly suggest a pivotal role for this potent regulator of growth and development. PMID- 1286615 TI - The Drosophila cdc25 homolog twine is required for meiosis. AB - We have identified a second cdc25 homolog in Drosophila. In contrast to string (the first homolog identified in Drosophila) this second homolog, twine, does not function in the mitotic cell cycle, but is specialized for meiosis. Expression of twine was observed exclusively in male and female gonads. twine transcripts are present in germ cells during meiosis, and appear only late during gametogenesis, well after the end of the mitotic germ cell divisions. The sterile Drosophila mutant, mat(2)synHB5, which had previously been isolated and mapped to the same genomic region as twine (35F), was found to carry a missense mutation in the twine gene. This missense mutation in twine abolished its ability to complement a mutation in Schizosaccharomyces pombe cdc25. Phenotypic analysis of mat(2)synHB5 mutant flies revealed a complete block of meiosis in males and severe meiotic defects in females. PMID- 1286616 TI - Biological and molecular correlates between induced dedifferentiation and spore germination in Dictyostelium. AB - When developing cultures of Dictyostelium discoideum are disaggregated at any time prior to cell wall formation and challenged to reinitiate development, amoebae will progress through the original sequence of morphogenetic stages, but the second time through they will do so in roughly one-tenth the original time, a process known as 'rapid recapitulation'. However, if disaggregated cells are suspended in nutrient medium, they enter a program of dedifferentiation during which they lose the capacity to rapidly recapitulate after an 80 minute lag period in a process known as 'erasure'. Here we show that cells that have completed the morphogenetic program and emerge from spore coats in the process of germination have also erased. In addition, the germination-specific 270 gene family is expressed during induced dedifferentiation in a unique fashion, and a germination-defective mutant exhibits a dramatic delay in erasure without concomitant defects in the program of gene regulation accompanying induced dedifferentiation. These results suggest for the first time that induced dedifferentiation and spore germination share some common processes in converting cells from a developmental to vegetative state. PMID- 1286617 TI - Induction of vasculogenesis and hematopoiesis in vitro. AB - Despite a large number of investigations of embryonic vascular development, in particular in avian embryos, the conditions under which the endothelial and hematopoietic cell lineages emerge remain unknown. As we demonstrate here, both endothelial and hematopoietic cells can be induced by treatment of dissociated quail epiblast with fibroblast growth factors in vitro. These cells aggregate in characteristic blood islands. In long-term culture, the induced endothelial cells gave rise to vascular structures in vitro, i.e. vasculogenesis. No induction was observed in the absence of fibroblast growth factors, and other growth factors like TGF-beta, TGF-alpha and EGF were not capable of inducing blood island formation. Thus, the dissociated quail epiblast provides a remarkably simple test system to investigate cell lineage diversification in higher vertebrates. PMID- 1286618 TI - Determination of epithelial half-somites in skeletal morphogenesis. AB - The segmental body plan of vertebrates arises from the metameric organization of the paraxial mesoderm into somites. Each mesodermal somite is subdivided into at least two distinct domains: rostral and caudal. The segmental pattern of dorsal root ganglia, sympathetic ganglia and nerves is imposed by differential properties of either somitic domain. In the present work, we have extended these studies by investigating the contribution of rostral or caudal-half somites to vertebral development using grafts of multiple somite halves. In both rostral and caudal somitic implants, the grafted mesoderm dissociates normally into sclerotome and dermomyotome, and the sclerotome further develops into vertebrae. However, the morphogenetic capabilities of each somitic half differ. The pedicle of the vertebral arch is almost continuous in caudal half-somite grafts and is virtually absent in rostral half-somite implants. Similarly, the intervertebral disk is present in rostral half-somite chimeras, and much reduced or virtually absent in caudal somite chimeras. Thus, only the caudal half cells are committed to give rise to the vertebral pedicle, and only the rostral half cells are committed to give rise to the fibrocartilage of the intervertebral disk. Each vertebra is therefore composed of a pedicle-containing area, apparently formed by the caudal half-somite, followed by a pedicle-free zone, the intervertebral foramen, derived from the rostral somite. These data directly support the hypothesis of resegmentation, in which vertebrae arise by fusion of the caudal and rostral halves of two consecutive somites. PMID- 1286619 TI - Molecular gradients along the proximal-distal axis of embryonic insect legs: possible guidance cues of pioneer axon growth. AB - It has been proposed that gradients of environmental cues direct the proximal growth of pioneer axons in embryonic insect legs. Hybridoma techniques have been used to produce 3 monoclonal antibodies (mAbs) that bind to components associated with the basal lamina/extracellular matrix that are non-uniformly distributed along the proximal-distal axis of cockroach legs at the time of pioneer axon growth. Two of these mAbs, PROD-1 and PROD-2, label the proximal parts of the leg more intensely than the distal ends. The other mAb, DIP-1, has the reverse pattern of binding with the distal parts of the leg labeled more intensely. The graded distribution of these antigens only occurs just prior to and during the growth period of the Ti1 pioneer axons. Western blot analyses and immunoprecipitations have identified the protein antigens recognized by these mAbs. The spatial and temporal distributions of these molecules in the legs and the CNS make them good candidates for environmental guidance cues of pioneer axon growth. PMID- 1286620 TI - Ontogeny of calbindin-D28K and calbindin-D9K in the mouse kidney, duodenum, cerebellum and placenta. AB - The appearance of the calcium-binding proteins (CaBP-D28K and CaBP-D9K) in embryonic mice tissues was determined using a sensitive immunohistochemical assay. CaBP-D28K first appears in myenteric nerve plexuses of the duodenum on day E15, in duodenal villus cells on day E16, in Purkinje cells of the cerebellum on day E19, in cells of the mesonephric duct on day E11 and in the metanephric duct on day E12. CaBP-D9K first appears in enterocytes of the duodenum on day E18, in trophoblastic giant cells (TGC) of the placenta on day E10, and in the metanephric duct on day E15. A differential time of appearance and colocalization of the two CaBPs is demonstrated in the embryonic mouse kidney, suggesting either that vitamin D does not control both CaBPs in the foetus or that the vitamin D control is unequal. The early appearance and location of CaBP-D9K in TGCs may suggest that these cells play an important role in transplacental transfer of calcium. PMID- 1286621 TI - Cytoarchitectural development of the human dentate nucleus: a Golgi study. AB - Golgi-stained sections of the human cerebellar dentate nucleus (DN) at various gestational ages were examined to study the dendritic proliferation and maturation of the DN neurons. Bipolar cells were seen at 14-15 weeks. By 19-20 weeks, three cell types were identifiable: bipolar, hemispheric and pyriform. The cells of the dorsomedial region matured earlier than those of the ventrolateral region. In addition to the above cell types, multipolar and nuclear boundary cells were observable at 24-25 weeks. The five cell types persisted during subsequent development. At no stage of development was any neuronal organizational pattern apparent. A remarkable dendritic proliferation occurred at 27-28 weeks. Spines and filiform processes were seen at 34 weeks of intrauterine life. PMID- 1286622 TI - First appearance of orthogonal arrays of particles in Muller cell membranes depends on retina maturation. AB - A freeze-fracture analysis was undertaken to investigate both the appearance of orthogonal arrays of particles (OAP) in the Muller cell endfoot membrane at the retina-vitreous border and the endfoot size during development of two avian species. Chickens and pigeons have a common length of development until hatching (21 days), but differ in maturation velocity. In the chicken, the first OAP appear in the central retina at embryonic day 18 (E18), in the peripheral retina at E19. The OAP density increases rapidly. In the pigeon, the first OAP appear 6 days after hatching when the eyes are opened. In both species, the size of endfeet is maximal when the OAP first appear and is reduced thereafter. In the chicken, during the time up to adulthood both the mean endfoot size and the retina area increase 6-fold suggesting that the number of endfeet remains constant during growth of their individual area. In the pigeon, after an initial increase of mean endfoot area this decreases until adulthood, despite continuous growth of the eye. This strongly suggests that during retina growth the number of Muller cell endfeet increases. It is concluded that these alterations of Muller cell membranes reflect some functional aspects of retina maturation. PMID- 1286623 TI - Naturally occurring degrading events in axon terminals of the dentate gyrus and stratum lucidum in the spiny mouse (Acomys cahirinus) during maturation, adulthood and aging. AB - The naturally occurring dynamics of presynaptic axon terminals were investigated in the dentate gyrus and stratum lucidum of the spiny mouse (Acomys cahirinus) during maturation, adulthood and aging. A sensitive and selective silver-staining technique was applied to analyze neuronal lysosome accumulation (LA), indicating synaptic degradation during development. LA was quantified by counting silver grains in the inner third and outer two thirds of the molecular layer, granular layer, and the infragranular layer of the dentate gyrus, and in the strata oriens, pyramidale, lucidum and radiatum of the medial and distal regio inferior on postnatal days 21, 28, 95, 730, and 1,460. In young and adult animals, LA was most abundant within the inner molecular layer. When animals grew older, LA densities obviously decreased in the inner molecular layer but increased in the outer molecular layer. Within the stratum lucidum only the distal regio inferior showed an extremely high LA density on postnatal day 21, dramatically decreasing thereafter and reaching adult low values during the first postnatal month. By electron microscopy in the inner molecular layer we found LA in large synaptic boutons and small terminals both with distinct synaptic contact zones. Degrading presynaptic profiles may further accumulate dense bodies, zones with completely disorganized cytoplasm, and lamellarly organized whorled membrane debris. In the distal regio inferior comparable phenomena were observed in typical mossy fiber boutons. Despite these degrading events, no electron-dense degenerating terminals were found. These results on naturally occurring nondegenerative synaptic degradation are discussed with current concepts of synaptic turnover and remodelling in the developing, adult and aging brain. PMID- 1286624 TI - Glycoprotein processing is required for completion but not initiation of oligodendroglial differentiation from its bipotential progenitor cell. AB - The role of N-linked glycoproteins in the development of oligodendroglia has been studied in a culture system that initially contains the progenitor cell for oligodendroglia and type 2 astrocytes. The progenitor cells, derived from mixed glial primary cultures of newborn rat cerebrum, were studied under culture conditions that we have shown previously to induce oligodendroglial differentiation. Castanospermine was used to inhibit processing of N-linked glycoproteins by its inhibitory action on glucosidase I, the enzyme responsible for the initial trimming of glucose residues from the glucosylated high mannose core oligosaccharide derived from the dolichol pathway. Exposure to castanospermine had no effect on the initial commitment of the progenitors to oligodendroglial differentiation, i.e. 95% of both control and castanospermine treated cells became galactocerebroside (GC) positive. However, the developmental inductions of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glycerol-3 phosphate dehydrogenase (GPDH) and the elaboration of a network of fine interconnecting processes were prevented by the castanospermine exposure. No effect of castanospermine on cell number was observed. A major effect of the inhibitor on glycoprotein processing was manifested by an accumulation of high mannose glycoproteins, of abnormal oligosaccharide structure, compatible with the inhibition of glucosidase I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286625 TI - Establishment of a culture system for the study of oligodendroglial development: complementary effects of boiled serum and astrocyte extract. AB - Mixed glial primary cultures derived from neonatal rat brain were used to isolate the progenitor glial cell with the capacity to differentiate into oligodendroglia or type 2 astrocytes depending on the culture medium. Subcultures composed primarily of this progenitor were utilized, first, to study the regulation of oligodendroglial differentiation by two factors added to chemically defined medium (CDM), i.e. boiled fetal calf serum (FCS) and cellular extract of type 1 astrocytes, and, second, to devise culture conditions that would cause the progenitor cells to differentiate virtually exclusively along oligodendroglial lines (judged by immunologically identified expression of galactocerebroside; GC) and with high specific and total activity of the oligodendroglial enzymes, 2',3' cyclic nucleotide 3'-phosphohydrolase (CNP) and glycerol-3-phosphate dehydrogenase (GPDH). Addition of untreated FCS to CDM of the progenitors resulted in 6 days in richly cellular, mixed glial cultures composed of slightly more GFAP-positive astrocytes than oligodendroglia. Addition of boiled FCS to CDM of the progenitors resulted in 6 days in cultures composed almost exclusively (95%) of GC-positive cells and with high specific activity of CNP. This effect of boiled serum, compared to untreated serum, was related to virtual elimination of astrocytes, in the presence of continued differentiation to GC-positive oligodendroglia. Addition of type 1 astrocyte extract as well as boiled FCS to CDM was necessary to generate high specific activity of GPDH. Additionally, the total number of oligodendroglia increased 2-fold when astrocyte extract as well as boiled FCS was added to the CDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286626 TI - Lack of cell density-dependent changes in gangliosides of rat primary culture neurons. AB - Cell density-dependent changes in neuronal gangliosides, primarily relating to neurite outgrowth under dense to sparse conditions, were examined at cell seeding densities over an 8-fold range. During the first 24 h of incubation, the dissociated fetal rat neurons showed characteristic protrusion of neurites as a function of cell density. Ganglioside and protein contents per the same cell numbers were higher in dense cultures than sparse ones. However, the ganglioside pattern was essentially unchanged from dense to sparse culture, showing a predominance of GD3 and GT1b. The biosynthetic activity of gangliosides, as estimated by the incorporation of 3H-labeled N-acetyl-D-mannosamine, a precursor of sialic acid, was similar at various cell densities, with the labeling of b series gangliosides predominating. The expression of neuronal gangliosides was monitored by indirect immunofluorescence using anti-GM1 antibody, but was found to be poor. A2B5 antigen, which was mainly identified as GT1b, appeared to be readily expressed on cell surfaces in sparse cultures. In contrast, the highly polysialylated form of the neural cell adhesion molecule (NCAM-H) was fully expressed on both the neurites and cell soma at various cell densities. The results suggest that the polysialic acids in NCAM have more important roles in neurite outgrowth than gangliosides, since the composition and synthesis of gangliosides are not affected by cell seeding density. PMID- 1286627 TI - Circumcision in women. PMID- 1286628 TI - The risk of medical complications after female circumcision. AB - The medical complications of the practice of circumcision were studied in 290 Somali women between ages of 18-54. Thirty-nine percent of the interviewed women had experienced significant complications after circumcision, most commonly haemorrhage, infection or urinary retention. Thirty-seven of the women reported a late complication of circumcision. Among these complications were dermoid cyst at the site of the amputated clitoris, urinary problems such as pain at micturition, dribbling urine incontinence and poor urinary flow. Forty of the women had experienced problems at the time of menarche and ten of them were operated because of haematocolpos. Most of the married women of the study sample were defibulated naturally by their husbands. PMID- 1286629 TI - Audit of hysterectomies at the Aga Khan Hospital, Nairobi: justification of operative indications. AB - An audit of 381 hysterectomies performed over a 5 year period (1986-1990) was carried out. In order to assess justification of the indication for hysterectomy pre-operative diagnoses were divided into two groups: those potentially confirmable by pathologic study and those not potentially confirmable by pathologic study. Out of the 273 cases studied in the first group, 246 (90.1%) were justified, while out of the 108 cases studied in the second group, 82 (75.9%) were justified. An overall 86% justification rate was observed. Adenomyosis as a histopathologic finding was seen more commonly in Asian than African patients (P < 0.005). Morbidity rate was 20% and there were no mortalities. The procedure in general was considered safe and justified. PMID- 1286630 TI - Tumours of the eye and orbit in Ibadan. AB - Four hundred and forty ocular and orbital tumours seen in Ibadan over 11-year period (1980-1990) are reviewed. Three quarters of the 252 patients who had enucleation had malignant neoplasms, of which 55% were retinoblastomas. The mean age of patients with retinoblastomas (3.2 years) was less than that of patients with carcinoma and malignant melanomas (47 years). Malignant melanomas were rare neoplasms in Ibadan. The commonest orbital lymphoma was Burkitt's lymphoma. Only 24% of the enucleated eyes had inflammatory conditions, of which 38% gave a positive history of trauma. Inflammatory lesions were the commonest benign ocular diseases accounting for 33% of these latter cases. Postmeasles keratitis was a significant associated finding in these patients. PMID- 1286631 TI - Post-operative management of pterygium in Jos, Nigeria--comparison of antibiotics, steroids and opticrom. AB - Eighty six patients with a total of 125 pterygium-affected eyes were treated by surgical excision and one of three post-operative topical, medical adjuvants- antibiotics, steroids or Opticrom--to try and control the recurrence rate. The result showed that opticrom 2% ophthalmic drops was most effective in controlling pterygium recurrence. Steroids proved more effective than antibiotics. PMID- 1286632 TI - Observations on the epidemiology of plague in Tanzania during the period 1974 1988. AB - Field and commensal rodents and shrews were live-trapped from selected areas in each of the six zones of the Republic, namely North-eastern, Eastern, Central western, South-western, Southern and Seaports. The captured animals, small ruminants, humans and small carnivores were serologically tested for specific plague antibodies, using the Passive haemagglutination (PHA) and Passive haemagglutination Inhibition (PHAI) techniques. Taxonomic studies and population densities of rodents and their ectoparasasites were carried out. A total of 5638 animals were captured and 79.9% of them were tested for plague. Of those tested, 2.4% contained agglutinating plague antibodies at serum dilutions of 1:20 and above. The positive rodents were found in Lushoto, Mbulu, Chunya and Monduli districts, as well as at Tanga seaport. These include R. rattus, M. natalensis, A. niloticus and Otomys spp. A total of 7480 human, 293 carnivorous and 425 small ruminant sera were also tested for plague. Seven (2.4%) of the carnivores were positive at serum titres of 1:20-1:80. All the small ruminants were negative. Likewise, 1.4% of the tested human sera contained specific plague antibodies at titres ranging from 1:20-1:60. Out of 6480 fleas collected from the captured small mammals, 5476 were identified. Of these, 34.5%, 20.4%, and 17.8% were X. brasiliensis, D. lypusus and X. cheopis respectively. It was generally concluded that plague was still endemic in several parts of the country, that some foci were active, and that there was a potential risk of accidental introduction and/or transfer of the disease into or out of the country. Establishment and maintenance of surveillance services and facilitating research and control programmes of the disease were recommended. PMID- 1286633 TI - Sources of intra-operative bacterial colonization of clean surgical wounds and subsequent post-operative wound infection in a Nigerian hospital. AB - The incidence of postsurgical clean wound infection in 101 consecutive operations was 1.98%. Staphylococci were the predominant bacteria cultured from the anterior nares of the patients and attending surgical personnel--and were found to colonize the wounds. The nasal carriage rates of Staphylococcus aureus amongst the patients and surgical staff were 12.1% and 17.% respectively. Group III and non-typeable (NT) S. aureus strains accounted for about 65% of S. aureus isolates cultured from the anterior nares. A low incidence of nasal carriage of S. aureus isolates correlated with low incidence of wound sepsis. The operating room air seemed considerably contaminated but this did not reflect in high incidence of postsurgical wound sepsis. Our results suggest patients microflora and operating room air were the major sources of intra-operative bacterial colonization of wound at this centre. PMID- 1286634 TI - The role of the laboratory in a Chlamydia control programme in a developing country. AB - The laboratory components of a Chlamydia trachomatis disease control programme for a developing country are reviewed. Early diagnosis of chlamydial infections is the most cost effective means of preventing the long term sequelae of trachoma, pelvic inflammatory disease, ectopic pregnancy and infertility, which are now a major public health burden to the health care system in developing countries. Public health strategies are required to establish both a co-ordinated limited system of laboratory services, and to promote the diagnosis and treatment of disease syndromes in the absence of laboratory support. Laboratory tests for the specific diagnoses of chlamydial infections requiring different levels of expertise and equipment can be instituted within settings appropriate to the resources and technical expertise available. Emphasis is given to appropriate cost effective utilization of laboratory testing. PMID- 1286635 TI - A prospective study of 110 Ethiopians with thyrotoxicosis. AB - One hundred and ten Ethiopian thyrotoxic patients were studied between February 1986 and January 1991 in a weekly endocrine clinic of Tikur Anbessa Teaching Hospital (TATH) in Addis Ababa, Ethiopia. This gives an incidence of 22 patients per year. There were 14 males and 96 females (M:F = 1:7). Fifty three patients (48.2%) had Graves' hyperthyroidism, 37 (33.7%) toxic multinodular goitre (TMNG), 14 (12.7%) toxic adenoma, 4 (3.6%) Jodbasedow phenomenon and 2 (1.8%) had thyroiditis. The mean age was 29.2 +/- 9.8 (+/- S.D.) years for Graves' cases, 49.0 +/- 10.9 years for TMNG cases and 46.4 +/- 15.9 years for toxic adenoma cases. The clinical presentation was similar to other reported series. The majority (88.7%) of Graves' patients were below 40 years while 75.7% of TMNG patients were over 40 years of age; this is in keeping with the observed younger age incidence of Graves' hyperthyroidism and older age incidence of TMNG. All patients responded to propylthiouracil therapy and no major side effect was recognized. Nine patients underwent sub-total thyroidectomy of whom one became hypothyroid a year later. One became toxic after a year, while 6 remained euthyroid 3 years after the surgery; the other patient did not return subsequently. The result of this study shows that thyrotoxicosis is not a rare condition in Ethiopia. PMID- 1286636 TI - The first ten years of heart surgery in Kenya--aspirations, dilemmas and possibilities. AB - This paper looks at the beginnings of cardiac surgery in Kenya with relevant clinical data as well as the overall historical background to various cardiovascular operations which preceded formal establishment of the Thoracic and Cardiovascular Surgical Unit at the Kenyatta National Hospital. Similar activities in other hospitals in Nairobi and elsewhere in Kenya have been excluded. The Unit separated from general surgical wards in January 1973. By the end of 1983, a total of 208 open heart operations had been done by various teams in the Unit. A number of other heart operations were also undertaken. Those done before that decade are also highlighted back to 1950. The many problems that the Unit faced and still faces are also identified in this paper and the dream of making it a Centre of Excellence revisited. PMID- 1286637 TI - Salivary gland tumours in Kenya. AB - Four hundred and seventeen tumours of salivary glands in Kenya were analysed. There is no evidence of higher incidence of salivary tumours than in non-African countries. The pattern of distribution differed from that of western countries, but in conformity with most African series showed a low proportion of tumours of the parotid gland and high proportion of tumours in the submandibular gland and the palate. The involvement of the palate by salivary gland tumour is very prominent in the African series and particularly more so in the females. Malignant tumours of the palate and parotid glands were frequent but were lower than those reported in other African series. On the other hand malignant salivary gland tumours of the submandibular glands while lower than those of the western countries, were higher than those of other African series. PMID- 1286638 TI - Inflammatory pseudotumour of the liver: a case report. AB - A case of inflammatory pseudotumour of the liver is reported. Together with a brief review of inflammatory pseudotumours we also present the clinical picture and pathologic findings of this very rare tumour-like condition with only 31 cases quoted in the medical literature. We also discuss the difficulty of making a correct diagnosis of the condition. PMID- 1286639 TI - Murder during sleep-walking. AB - The issue of criminal responsibility is no easy matter to resolve at times. One such instance is offered by the case of the sleep walker who commits a violent act in the course of his sleep. However, sleep-walking disorder has not received much professional attention. In this article the author reports one case of sleep waking disorder (Somnambulism) in which murder was committed in cold blood. PMID- 1286640 TI - The effect of nocotiana tabacum (snuff) on blood pressure and pulse rate of Nigerians. AB - Nutritional and environmental factors are now known to affect the blood pressure and pulse rate of man. The present study investigated the effect of nicotiana tabacum on these parameters. Thirty-three male Nigerians (20-68 years) living in Calabar, Nigeria were used for this study. The subjects were treated at three different periods with snuff containing varied concentrations of Natron (0.5g and 10g/100g of snuff) and their systolic and diastolic pressures as well as pulse rate were measured at intervals of 30 minutes up to a maximum of 90 minutes. Each subject served as his own control. There were significant and time-dependent increases in the parameters measured. In addition, the increases were more marked in the absence of Natron than in its presence. PMID- 1286641 TI - Phantom pregnancy at Muhimbili. AB - This is a case report on phantom pregnancy at Muhimbili. Relevant factors pertaining to personality of the patient, the experienced psycho-social stresses, the medical history and possible causes of symptom formation culminating in pseudocyesis are looked into and discussed. PMID- 1286642 TI - Rat bite fever: a case report of a Kenyan. AB - Rat bite fever has not been reported from Kenya previously. A case of 17 year old Kenyan male who was diagnosed to have rat bite fever after a bite of domestic rat is described. The history, clinical features and demonstration of spirillum like organisms from a thick blood film suggest infection due to spirillum minus. The patient recovered completely after a course of penicillin and gentamicin. PMID- 1286643 TI - Vitamins for newborn infant formulas: a review of recommendations with emphasis on data from low birth-weight infants. PMID- 1286644 TI - Parenteral nutrition: an update. PMID- 1286645 TI - Prophylaxis of allergic disease--is it worthwhile? PMID- 1286646 TI - Energy requirements and energy expenditure in infancy. PMID- 1286647 TI - Aluminium in infant feeding: is it a problem? PMID- 1286648 TI - Bone mineralization and growth. PMID- 1286649 TI - Lipids in human milk: a model for infant formulae? PMID- 1286650 TI - Nutrition in early life and later outcome. PMID- 1286651 TI - Iron deficiency in infancy; easy to prevent--or is it? AB - Despite major advances in our knowledge of iron nutrition in infancy, iron deficiency remains a significant problem in the UK. The precise size of the problem is unknown, but there appears to be a higher risk amongst certain ethnic groups. Nutritional iron deficiency appears after the age of 6 months and is undoubtedly linked to inappropriate feeding practice. High bioavailability of iron in weaning foods is of paramount importance in preventing iron deficiency, whether using family foods or commercially available products, and further information about different foods and diets is needed. The long-term detrimental effect on mental development makes prevention of iron deficiency a high priority public health objective for the 1990s. PMID- 1286652 TI - Conserving breasts and relationships. PMID- 1286653 TI - Mastectomy versus breast conservation surgery: mental health effects at long-term follow-up. AB - Between 1984 and 1989, 129 Stage 1 and Stage 2 breast cancer patients were entered into a behavioral study in Pittsburgh. Approximately 70% of these patients had elected to have breast conservation (lumpectomy) surgery, with the remainder choosing mastectomy. Using the Profile of Mood States, a measure of perceived social support, and Karnofsky ratings of physical functional status, patients were assessed 3 to 5 days following surgery and again 3 and 15 months following surgery. The data were analyzed using a repeated-measures analysis of covariance, adjusting for aggressiveness of chemotherapy. Compared to mastectomy patients, patients who received breast conservation surgery were rated as more functional by observers, but they perceived themselves as having less energy and less emotional support, especially over the first 3 months of the recovery period. Because there is accumulating evidence that emotional support may act as a stress buffer in various populations and may have survival value, these findings may be particularly troublesome. This study shows that breast conservation surgery is not a psychosocial panacea. Patients whose breasts are spared, especially younger patients, have psychological symptoms that appear acutely worse in the short run and, in the end, are similar to those of patients who elect to have mastectomies. Therefore, patients choosing lumpectomies are not necessarily psychosocially better off than those electing to have mastectomies. Additionally, these patients, particularly younger patients, may require greater social support and potential mental health interventions than they seem to be receiving. PMID- 1286654 TI - Acute exercise: buffering psychosocial stress responses in women. AB - We evaluated the experimental hypothesis that an acute bout of aerobic exercise (AE) serves as a buffer to psychosocial stress responses in low to moderate physically fit women. Forty-eight (24 White, 24 Black) 25- to 40-year-old women participated in two counterbalanced experimental conditions: an attention control and a 40-min bout of AE at 70% heart rate (HR) reserve. The attention control and AE treatments were followed by (a) 30 min of quiet rest, (b) exposure to mental and interpersonal threat, and (c) 5 min of recovery. Blood pressure (BP) and HR were monitored at baseline, during the stressors, and throughout recovery. Self reported distress was assessed before each stressor and upon completion of the recovery period. The results provided clear evidence that exercise dampens BP reactivity to psychosocial stress. Additionally, compared with the attention placebo control, AE reduced both the frequency and intensity of anxiety-related thoughts that occur in anticipation of interpersonal threat and challenge. PMID- 1286655 TI - Health beliefs and promotion of HIV-preventive intentions among teenagers: a Scottish perspective. AB - Beliefs concerning the spread of the human immunodeficiency virus (HIV) and preventive behaviors were examined in a sample of 351 sexually active Scottish teenagers. A postal questionnaire, including measures of variables specified by the health belief model (HBM) and preventive intentions, was employed. The relation between HBM measures and reported endorsement of HIV-preventive intentions was investigated. Results indicated that, in general, respondents intended to use condoms with new sexual partners. The majority also intended to carry condoms if they thought they might have sex with a new partner and to ask potential partners about their previous sexual history. Multiple-regression analyses showed that measures of health beliefs, gender, age, sexual experience, and previous condom use accounted for 17.8% to 24.3% of the variance in reported preventive intentions. Perceived barriers to preventive behaviors were found to be important predictors. However, the overall pattern of results raised questions concerning the adequacy of the HBM as a model of the determinants of HIV preventive intentions, and the need for an extended model is discussed. Separate analyses were conducted for men and women and for 16- and 18-year-olds, and the implications for modeling intention formation in these subgroups are considered. The relevance of these findings to HIV-preventive campaigns is also discussed. PMID- 1286656 TI - Changing knowledge and attitudes about skin cancer risk factors in adolescents. AB - We examined knowledge, attitudes, and behaviors related to skin cancer, sun exposure, sunscreen use, and use of tanning booths in 903 female and 800 male adolescents. The effectiveness of a brief, school-based intervention designed to increase teens' knowledge and preventive attitudes about skin cancer was also evaluated. Females, older students, and those with high-risk skin types were most likely to use sunscreen and to take precautions. However, overall level of protection was low. Intentions to take precautions were associated with levels of perceived susceptibility to skin cancer, attitudes about the benefits of sun exposure, skin type, and sex. Beyond intentions, sunscreen use was associated with perceived susceptibility and skin type. The one-session, school-based intervention significantly increased knowledge and perceived susceptibility to skin cancer but not behavioral intentions. PMID- 1286657 TI - On becoming involved with drugs: modeling adolescent drug use over time. AB - We tested a model of the process of becoming involved with drugs during junior high. The sample included 698 students who were not using alcohol, cigarettes, or marijuana during Grade 7 (T1); the follow-up data points were 12 and 15 months later (T2 and T3). The final model, which predicted 72% of the variance in drug use at T3, provides support for hypotheses drawn from both social and cognitive theories. Weak familial and school attachments fostered use by increasing the likelihood of exposure to pro-drug social influences (drug use offers); weak bonds with school also directly affected cognitive motivations (lower resistance self-efficacy [RSE] and more positive outcome expectancies). In turn, social influences at T1 played a dominant role in initial use at T2, but cognitive motivations were also significant. At T3, prior use assumed the most prominent position. Drug-specific measures of RSE and expected use directly affected later use of that substance. The results indicate that both generic and drug-specific effects are needed to explain adolescent drug use. Implications for prevention programs are discussed. PMID- 1286658 TI - The stages and processes of exercise adoption and maintenance in a worksite sample. AB - We applied the model of the stages and processes of change to exercise adoption and maintenance. This model has shown promise in advancing theory and treatment of the addictions and other negative health behaviors, but there have been few systematic attempts to apply the model to positive health behaviors, such as exercise adoption. Questionnaires dealing with the stages and processes of exercise change were developed and administered to a sample of 1,172 participants in a worksite health promotion project. The sample was split randomly into halves for (a) initial model development and testing and (b) confirmatory measurement model testing. Additional model confirmation was obtained by examining the hierarchical structure of the processes of change and by conducting Stage x Process analyses. Results suggest that the underlying constructs derived from smoking cessation and other addictive behaviors can be generalized to exercise behavior. Understanding the stages and processes of exercise behavior change may yield important information for enhancing exercise adoption, adherence, and relapse prevention at both individual and public health levels. PMID- 1286659 TI - An educational test of health behavior models in relation to emergency helping. AB - This study used a true experimental design to evaluate the quality and occurrence of emergency helping behavior among university first-aid students in response to a supplemental educational unit designed to improve bystander helping. The educational unit addressed the inhibitors of emergency helping behavior within the framework of bystander behavior models and was delivered using several behavior modification strategies. Using chi-square analysis, it was found that the 43 treatment students exposed to the supplemental unit responded appropriately to a simulated emergency more often than 41 similar control students not exposed to the unit (32.6% vs. 7.3%, p = .004) and that the effect was confined primarily to women (p = .001). Future emergency care education incorporating similar theory-based educational strategies might improve trained bystander responsiveness and thus enhance the efficiency of prehospital care. Theoretical and future research implications are discussed. PMID- 1286660 TI - Patterns of social desirability and anger in young men with a parental history of hypertension: association with cardiovascular activity. AB - We identified, via cluster analysis, subgroups of young men with a parental history of hypertension (PH+) who differed in their profiles of need for approval, covert experience of anger, and extent to which they express anger when provoked. The PH+ subgroup with high need for approval and low anger acknowledgment scored higher on denial but lower on measures of angry temperament and overt display of anger than did the PH+ subgroup with low need for approval and high anger acknowledgment or men without a parental history of hypertension (PH-). Moreover, the PH+ subgroup with high need for approval and low anger acknowledgment manifested significantly higher stressor-induced blood pressure (BP) responsivity than did the other two groups. Possible relations between parental history status, need for approval, anger, BP reactivity, and essential hypertension are discussed. PMID- 1286661 TI - Stages of readiness to quit smoking: population prevalence and correlates. AB - We examined the population prevalence and correlates of stages in smokers' readiness to quit, using data from 1,048 smokers recruited in a self-weighting, multistage, systematic clustered area sample from 0.44% of South Australian dwellings, with an 89% response rate. Smokers in the precontemplation stage comprised 24.1% of the sample, smokers in the contemplation stage comprised 47.2%, and smokers in the preparation stage comprised 28.7%. No sociodemographic variables (i.e., age, sex, marital status, educational level) were found to be significant independent predictors of membership in the different stages. The five significant independent predictors of being in the precontemplation stage (vs. the contemplation stage) were (a) having a higher confidence of quitting, (b) seeing fewer health risks associated with smoking, (c) not having made an attempt to quit, (d) seeing quitting as more difficult, and (e) smoking 25 or more cigarettes a day. The two significant independent predictors of being in the contemplation stage (vs. the preparation stage) were (a) having lower confidence of quitting and (b) not having tried to quit. We discuss implications for the understanding of smoking behavior in populations and also consider how cessation campaigns might address the factors associated with different stages of readiness to quit. PMID- 1286662 TI - Relation of level of exercise, age, and weight-cycling history to weight and eating concerns in male and female runners. AB - We examined the association between level of exercise and degree of weight preoccupation in a large sample of male and female runners, as well as risk factors posited to influence weight and eating concerns in the general population. Subjects were 2,459 males and 1,786 females who had completed a questionnaire on weight and eating concerns in a national running magazine. Eight percent of the males and 24% of the females had symptomatic scores on the Eating Attitudes Test (EAT). Exercise level, defined as weekly running mileage, was positively associated with excessive weight and eating concerns in males but not in females. Both sexes with a history of weight cycling were more likely to have symptomatic EAT scores than those with no such history. These results highlight the importance of studying these concerns in males as well as females and of examining the role of exercise level and weight-cycling history in the development of serious weight preoccupations. PMID- 1286663 TI - Human cerebrospinal fluid protein database: edition 1992. AB - Two-dimensional electrophoresis maps of human cerebrospinal fluid proteins are presented in the form of labeled images. 931 protein spots are identified in spinal fluid from a normal volunteer. Distinct spots that represent variants of the same protein, especially posttranslational modifications, are estimated to reduce the 931 different spots to < 200 different proteins. 248 spots of 29 protein groups have been identified and are indicated on enlargements of specific gel regions. The distribution of protein abundance, mass, charge and shape characteristics of these normal 931 spinal fluid spots are graphically profiled. Analysis of the shape parameter "vertical height: width ratio" reveals that a ratio > 3.5 correlates with glycoproteins, enabling their identification simply by image analysis. Proteins that are not present on the normal map, but appear in spinal fluid in patients with schizophrenia and Creutzfeldt-Jakob disease are illustrated on additional maps. PMID- 1286664 TI - The gene-protein database of Escherichia coli: edition 5. AB - The gene-protein database of Escherichia coli is both an index relating a gene to its protein product on two-dimensional gels, and a catalog of information about the function, regulation, and genetics of individual proteins obtained from two dimensional gel analysis or collated from the literature. Edition 5 has 102 new entries--a 15% increase in the number of annotated two-dimensional gel spots. The large increase in this edition was accomplished in part by the use of a new method for expression analysis of ordered segments of the E. coli genome, which has resulted in linking 50 gel spots to their genes (or open reading frames) and another 45 to specific regions of the chromosome awaiting the availability of DNA sequence information. Communication of information from the scientific community resulted in additional identifications and regulatory information. To increase accessibility of the database it has been placed in the repository at the National Center for Biotechnology Information (NCBI) at the National Library of Medicine under the name ECO2DBASE. It will be updated twice yearly. This edition of the gene-protein database is estimated to contain entries for one-sixth of the protein-encoding genes of E. coli. PMID- 1286665 TI - Workshop on two-dimensional gel protein databases. AB - A workshop on two-dimensional gel electrophoresis (2-DE) protein database, organized by the Committee on Data for Science and Technology (CODATA) of the International Council of Scientific Unions Task Group on Biological Macromolecules, was held at the CODATA Secretariat in Paris on March 9, 1992. Eleven scientists from eight different countries represented various aspects of 2 DE analysis--namely, cellular protein database development and protein microsequencing methodologies. The purpose of the workshop was to explore means of integrating the rapidly expanding body of information on 2-DE resolved proteins from different laboratories. A major proposal emanating from the workshop was the establishment of an intermediary or "relational" 2-DE gel protein database. This intermediary database, which would catalogue pertinent information on 2-DE resolved proteins (experimental source, 2-DE loci, biological information, etc.) could be an adjunct to, and accessed through, the existing international protein sequence databanks. It would function as a pointer for researchers to the individual 2-DE protein databases where primary and more specialized 2-DE data would be housed. PMID- 1286666 TI - The human keratinocyte two-dimensional gel protein database (update 1992): towards an integrated approach to the study of cell proliferation, differentiation and skin diseases. AB - The master two-dimensional gel database of human keratinocytes currently lists 2980 cellular proteins (2098 isoelectric focusing, IEF; and 882 nonequilibrium pH gradient electrophoresis, NEPHGE) many of which correspond to posttranslational modifications. About 20% of all recorded proteins have been identified (protein name, organelle components, etc.) and they are listed in alphabetical order together with their M(r), pI, cellular localization and credit to the investigator(s) that aided in the identification. Also, we have listed 145 microsequenced proteins that are recorded in this database. As an aid in localizing the polypeptides we have included blow-ups of the master images (IEF, NEPHGE) displaying all the protein numbers. In the long run, the master keratinocyte database is expected to link protein and DNA sequencing and mapping information (Human Genome Program) and to provide an integrated picture of the expression levels and properties of the thousands of proteins that orchestrate various keratinocyte functions both in health and disease. PMID- 1286667 TI - Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. AB - Microsequencing of proteins recovered from two-dimensional (2-D) gels is being used systematically to identify proteins in the master human keratinocyte 2-D gel database. To date, about 250 protein spots recorded in human 2-D gel databases have been microsequenced and, of these, 145 are recorded in the keratinocyte database under the entry partial amino acid sequence. Coomassie Brilliant Blue stained protein spots cut from several (up to 40) dry gels were concentrated by elution-concentration gel electrophoresis, electroblotted onto PVDF membranes and digested in situ with trypsin. Eluting peptides were separated by reversed-phase HPLC, collected individually and sequenced. Computer search using the FASTA and TFASTA programs from Genetics Computer Group indicated that 110 of the microsequenced polypeptides shared significant similarity with proteins contained in the PIR, Mipsx or GenEMBL databases. Only 35 polypeptides corresponded to hitherto unknown proteins. Peptide sequences of all 145 proteins are listed together with their coordinates (apparent molecular weight and pI) in the keratinocyte database. PMID- 1286668 TI - Mouse liver protein database: a catalog of proteins detected by two-dimensional gel electrophoresis. AB - Alterations in the abundance or structure of mouse liver proteins are being studied using two-dimensional gel electrophoresis (2-DE) to build a database of protein changes correlating with exposure to ionizing radiation or toxic chemicals. Thus far, studies have included the analysis of proteins from the offspring of exposed parents or from the exposed individuals themselves. In order to characterize and identify proteins found altered by such exposures, sex- and strain-related differences in protein patterns have been analyzed, and the subcellular locations of a large portion of the mapped proteins have been determined. As part of these studies, data are collected and stored using a variety of computer hardware and software tools that allow the accumulation of information on the origin of samples, gel identification, experiment description, and protein similarities and differences. This accumulation of information constitutes the mouse liver protein database. Relational database software is used to tie the different facets of the database together so that the results of a variety of experiments can be compared and interrelated. The database optimizes the information obtained from 2-DE gel sets by allowing use of the data for many purposes, including monitoring of gel resolution to ensure the collection of high quality data and correlation of protein effects induced by different agents. This first edition of the Argonne National Laboratory mouse liver protein database lays the foundation for future work and communication that should elucidate the significance of observed protein effects as possible markers of exposure to toxic agents. PMID- 1286669 TI - Human liver protein map: a reference database established by microsequencing and gel comparison. AB - This publication establishes a reference human liver protein map obtained with immobilized pH gradients. By microsequencing, 57 spots or 42 polypeptide chains were identified. By protein map comparison and matching (liver, red blood cell and plasma sample maps), 8 additional proteins were identified. The new polypeptides and previously known proteins are listed in a table and/or labeled on the protein map, thus providing a human liver two-dimensional gel database. This reference map can be used to identify protein spots on other samples such as rectal cancer biopsies. PMID- 1286670 TI - Inhibition of lipid deposition in the hypercholesterolemic rat by clentiazem, a calcium channel blocker. AB - We studied the effects of clentiazem, a calcium channel blocker (1) on the accumulation of lipid in the aorta, (2) on the level of plasma lipids, and (3) on the number of adherent intimal monocytes and foam cells. Seventy Wistar rats were assigned to one of the following groups: (1) regular diet, (2) an atherogenic diet consisting of regular chow with 2% cholesterol, 1% cholic acid, and 0.5% thiouracil (CCT), (3) CCT supplemented with 5 mg/kg/day clentiazem, and (4) CCT with 25 mg/kg/day clentiazem. Animals were sacrificed after 6 or 12 weeks of diet. Aortas were studied by light microscopy after staining with oil red O (ORO) and/or hematoxylin. ORO staining was quantified in both abdominal and thoracic regions of the aorta. The aortas of the clentiazem groups demonstrated significantly less ORO staining than CCT diet controls in thoracic aorta after 6 weeks and abdominal aorta after 12 weeks. There was no significant difference in the plasma lipid concentrations. The clentiazem-treated groups had fewer numbers of adherent monocytes and foam cells. We conclude that clentiazem inhibits lipid deposition in cholesterol-fed rats without lowering plasma lipid concentrations and that the number of intimal monocytes and foam cells is decreased in the presence of this calcium antagonist. PMID- 1286671 TI - Quantitative alteration of some aortic intima proteins in fatty streaks and fibro fatty lesions. AB - Proteins from grossly and histologically normal human aortic intimas and human aortic intima with fatty streaks or fibro-fatty lesions were extracted with 9 M urea mixture. Protein extracts were mixed with an internal absorbance calibrator (carbonic anhydrase) and subsequently separated by two-dimensional gel electrophoresis, silver stained, and quantitated by a laser beam densitometer. The vascular-origin proteins actin, tropomyosin-like proteins, tubulin, glycoprotein G35, and two myosin light chains were present in the highest amounts in normal aortic intima (27-year-old male). Quantitation of vascular-origin proteins in aortic intima with a fibro-fatty lesion from the same subject showed a slight decrease in relative amount of these proteins as compared to the normal intima. Several polypeptides (P15, P18, P60, P110b) and plasma-derived proteins not observed in the normal intima were found in fibro-fatty lesion (albumin, haptoglobin beta-chain, fibrinogen beta-chain, alpha 1-HS-glycoprotein). Other proteins which were present in very low amounts in the normal intima (transferrin, alpha 1-antitrypsin, apolipoprotein A-1, P56, P190) were found to be major proteins of intima with fibro-fatty lesion. Differences in relative amount of plasma-derived and vascular-origin proteins between normal intima and intima with fatty streaks, studied in a large number of specimens from 38 thoracic intimas and 18 paired abdominal intimas (16-34 years old) were less prominent. Statistically significant increases of the albumin/actin ratio were found in fatty streaks as compared to paired normal intimas as well as in the mean value of albumin/actin ratio in the group of fibro-fatty lesions (mean = 6.1) as compared to the group of fatty streaks (mean = 1.7) or normal intima (mean = 0.7). Several lesion unique proteins were observed; however, the frequency of the occurrence of these proteins in 41 specimens with lesion was low. No significant differences were observed in intima protein pattern and quantities of selected intima proteins between paired thoracic and abdominal aortas. PMID- 1286672 TI - Glucose and glucose analogs modulate collagen metabolism. AB - Patients with diabetes often develop complications involving collagen-containing connective tissues. Previous in vitro studies have demonstrated that glucose inhibits collagen fibril formation and subsequent cross-linking. Collagen with diminished cross-linking is more susceptible to collagenolytic degradation. This may underlie the decreased collagen levels. To test this hypothesis, D-glucose and its two analogs, L-glucose and 2-deoxy-D-glucose, were used in chick calvaria organ cultures to examine parameters of collagen metabolism. L-Glucose is not used by the cell and functions as an extracellular glucose-like molecule, while 2 deoxy-D-glucose inhibits normal D-glucose uptake by blockading the glucose transport mechanism. Each of these three sugars had the ability to inhibit collagen fibril formation. D-Glucose stimulated collagen synthesis; L-glucose had no effect; and deoxyglucose inhibited collagen synthesis. D-Glucose was able to reverse the inhibitory effect of deoxyglucose. D-Glucose did not change levels of degradation of newly synthesized collagen while both L-glucose and deoxyglucose stimulated collagen degradation. When glucose transport was inhibited by deoxyglucose, collagen degradation was further enhanced. We suggest that decreased collagen levels in the connective tissues of diabetics may result from a combination of inhibition of collagen fibril formation and subsequent cross linking, as well as increased collagen degradation. PMID- 1286673 TI - Microvascular changes in rat glomeruli as a consequence of small differences in selenium exposure. AB - This paper evaluates the effect of small differences in selenium exposure, within the safe range, on the glomerular vascular tufts of rats fed high-sucrose diets. In the first experiment male Wistar rats were housed in galvanized cages and were provided sucrose-based diets to induce a mild chronic insult to the microcirculation. One group of rats received the diet prepared to contain 0.10 mg Se/kg and another group 0.21 mg Se/kg. To assure that the galvanized metal cages were not influencing the results of the experiment this protocol was repeated in a second experiment wherein rats were housed in stainless steel cages. The levels of Se used supported normal activity of the long-term indicator of Se sufficiency, erythrocyte glutathione peroxidase. In both experiments rats fed diets containing 0.21 mg Se/kg had larger Bowman's capsules (P < 0.01) and vascular tufts (P < 0.01). Vascular tufts from these rats also contained a higher proportion of open capillary lumen (P < 0.01), contained less cytoplasmic and extracellular material (P < 0.001), and had larger nuclei (P < 0.001) than those fed 0.10 mg Se/kg. A third study was designed to determine if the selenium dependent differences in nuclear size were indicative of this being a site of incorporation. Year-old rats subjected to the same protocol as those in the second experiment were given 75Se, by injection into the femoral vein, to label the sites of incorporation. Glomeruli were purified and subjected to subcellular fractionation. Ninety percent of the radioactivity was associated with the crude nuclear fraction. Purification of the crude nuclear fraction demonstrated that the radioactivity was associated with the nuclei. PMID- 1286674 TI - The study of G6PD in erythrocyte and lens in senile and presenile cataract. AB - The G6PD activity of erythrocytes in 113 male patients with senile and presenile cataract and 86 controls, and G6PD activity of lens in 30 patients with senile cataract and 42 controls were reported. The cataractous group had higher frequency of G6PD deficiency and lower average G6PD level in erythrocytes and lenses, but without statistical significance. The frequency of G6PD deficiency of erythrocytes in presenile cataractous group was higher than that of senile cataractous group but with no statistical significance too. However, the average G6PD level of erythrocytes in presenile cataractous group was lower than that of senile cataractous group and with statistical significance (P < 0.05). The G6PD activity of lenses only presenile in the cortex and have a positive correlation with that of erythrocytes. There was a case with deficiency of G6PD both of erythrocytes and cataractous lenses in both eyes. The results indicate that the deficiency of G6PD might be one of the cataractous pathogenetic factor for presenile cataract. Measurement of G6PD activity of erythrocytes among population might be of significance in finding the risk factor for cataract. PMID- 1286675 TI - Purification of bovine interphotoreceptor retinoid-binding protein and its uveitogenicity in Lewis rats. AB - Interphotoreceptor retinoid-binding protein, IRBP, not only functioning as a shuttle to carry the retinoid between photoreceptor cells and pigment epithelium, but also inducing experimental autoimmune uveoretinitis (EAU), was purified by ConA Sepharose affinity chromatography from the fractions containing IRBP obtained in the course of ion-exchange chromatography by which the bovine retinal S-antigen was purified. This much simplified method allows more rapid purification of the two kinds of protein. EAU was successfully induced with injecting 50 micrograms of IRBP emulsified with Freund's complete adjuvant into the right hind footpads of Lewis rats. It was characterized by panophthalmia or endophthalmia with the severest damage in the posterior retina. Lymphocytes, mononuclear and polymorphonuclear cells were found to be the inflammatory cells of infiltration, with lymphocytes being predominant. PMID- 1286676 TI - Epidemiology of glaucoma in Asia-Pacific. AB - Primary open angle glaucoma is the second most important cause of permanent blindness in the Asia Pacific region. Thus it is very important to identify epidemiological and other risk factore which are associated with open angle glaucoma. The risk for glaucoma optic nerve damage increases with the age and with the level of the intraocular pressure. In this paper, I will highlight our study of several risk factors for development of the open angle glaucoma like (1) elevated intraocular pressure, (2) myopia, (3) suspicious large optic disc cup, (4) cupping with disc haemorrhages and (5) nerve fibre defect. The general and systemic conditions which are implicated as risk factore are (1) family history of glaucoma, (2) increase in age, (3) diabetes mellitus, (4) cardio vascular conditions like central retinal vein occlusion etc. (5) the endocrine disorders with increased thyroid and increased cortico steroids responsiveness in patients with glaucoma will be discussed. PMID- 1286677 TI - Complications and management of the filtration bleb. AB - Filtration surgery is the commonest operation performed for closed angle or open angle glaucoma when medical treatment or laser trabeculoplasty has failed to control the intraocular pressure. It is characterized by the formation of an artificial drainage fistula between the anterior chamber and subconjunctival space. The successful operation is evidenced by the appearance of a subconjunctival filtration bleb which in turn depends on the patency of this pathway. Despite numerous modification, the procedure trabeculectomy first described by Sugar in 1961 and later on popularized by Watson and Cairns in 1968 is the most popular filtration surgery performed nowadays. It is a safe, relatively easy operation which carries a success rate of around 76% to 84% with a small complication rate. Repeat filtration surgery, however, is often less successful, making a successful initial surgery critically important. A successful outcome of filtration surgery can be enhanced by preoperative preparation, meticulous technique with modification for individual case, and early identification and prompt treatment of the complications arisen. PMID- 1286678 TI - Advances in management of retinoblastoma. AB - Retinoblastoma is a highly malignant intraocular tumor of children that requires accurate diagnosis to prompt treatment. This article reviewed clinical, pathological and follow-up data on 1 147 cases of retinoblastoma registered in Japan from 1975 to 1982. It is obvious that the prognosis of children with retinoblastoma has improved remarkably in recent years. The current advances in the management of the retinoblastoma were discussed. PMID- 1286679 TI - The prevention of blindness--past, present and future. AB - Prevention of blindness is the most important aim of ophthalmology. Prevention of blindness is related to many factors. It is related to many factors, such as science and technology, economy and social behavior. There are worldwide activities by WHO, NGOs and other functions to promote the prevention of blindness in the world. More than 90% of blind population lives in developing world. Cataract is the top causes of blindness which is curable. Onchocerciasis is an endemic disease in west Africa and central America. Onchocerca Control Project (OCP) was formed in 1974 under WHO for the control of oncocerciasis by the funds of developed countries. The control of vector (simulium) as well as new drug are giving the the project the prospect of success in eradicating the disease, thus preventing the blindness by diseases. The situation on blindness by trachoma, childhood blindness, glaucoma, diabetes will be discussed. The progress of molecular genetics of eye disease may open the gate for prevention of blindness by these disease in future. PMID- 1286680 TI - The electrophysiology in idiopathic senile macular hole. AB - Of 12 patients with idiopathic senile full-thickness macular hole, 3 had bilateral involvement, 9 had monocular macular hole. Flash ERG and pattern VEP were performed in the bilateral eyes of all patients. The abnormal rate of the pattern VEP was 93.3% when we used 15' checkboard stimulus, the changes of the VEP appeared as delayed latencies, reduced amplitudes or malformation of P100. The abnormal rate of the flash ERG was 53.3%, showing primary characteristics of reduced amplitudes of cone response b-wave. There was statistically significant difference between the abnormal rates of the VEP and the ERG (P < 0.05). The halo diameters of the macular hole were significantly related to the latencies of P100 (P < 0.01), but there was no correlation between the hole diameter and the latencies of P100. In 9 fellow eyes which did not form macular hole, 3 eyes had the abnormal pattern VEP, including one eye having formed macular cyst. The results show that, in idiopathic senile macular hole, the pattern VEP provides more functional information than does the ERG, and prompts the importance of close follow-up of fellow eye. PMID- 1286681 TI - Use of perfluorocarbon liquids in complicated retinal detachments. AB - We now have an additional tool to help in managing complicated retinal detachments. We look forward to the day when we can leave the liquid without having to remove it because of the possibility of ocular complications. PMID- 1286682 TI - Branch retinal vein occlusion and its management. AB - The natural course of Branch Retinal Vein Occlusion is determined by the site and completeness of the occlusion, the integrity of arterial perfusion to the affected sector and the efficiency of the developing collateral circulation. Most patients with tributary vein occlusion have some capillary fall out and microvascular incompetence in the distribution of the affected retina and vision is significantly compromised in over 50% of patients who have either chronic macular oedema or ischemia involving the perifoveolar arcades. Retinal and capillary vasoproliferation with or without intraretinal or preretinal membrane formation are common sequelae, where inner retinal ischemia is extensive and vitreous hemorrhage is often a distinct threat to vision. Treatment of the sequelae of vein occlusion are largely centered on laser photocoagulation to diseased retina to limit fluid accumulation and abolish preretinal and papillary neovascularization. Vitrectomy and retinal detachment procedures are occasionally required in patients with uncontrolled vitreous hemorrhage and retinal membrane formation which threatens the integrity of the macula. A small proportion of patients with vein occlusion subsequent to vasculitis require medical therapy. PMID- 1286683 TI - Detection of gene alteration for color vision defects by polymerase chain reaction. AB - According to the fact that the abnormalities of visual pigment genes were always involved in the changing of the exon 5, two oligonucleotide primers were designed to amplify the exon 5 of red pigment gene and green pigment gene. After electrophoresis of the PCR products digested with Rsal or Sau3A, the DNA fragments from the exon 5 of red pigment gene (RPG) and green pigment gene (GPG) were separated since there are different restriction endonuclease sites. On the other hand, we analyzed the exon 5 related fragment by Southern blot hybridization with probe out of the 3' end of the fourth intron of green pigment gene. The results of PCR are consistent with nucleic acid hybridization. PCR technique will be of value in prenatal evaluation and genetic counselling. PMID- 1286684 TI - [A decrease in cardiac sensitivity after ischemia to a change in the extracellular concentration of calcium ions]. AB - Reperfusion of the heart 30 min. after ischemia causes slight recovery of contractility and content of macroergic compounds in the myocardium tissue. Recovery of perfusion by the hypercalcium medium (0.05 mol/l) improves metabolism of the myocardium 30 min after ischemia. However, further perfusion by solution with physiological content of Ca2+ is followed by the development of the myocardium contracture, essential decrease in extracellular concentration of ATP and phosphocreatine. An increase in the extracellular sodium concentration and addition of macroergic compounds (ATR, phosphocreatine) adenosine, when reperfusing the heart by hypocalcium solution, improve the postischemic state of the myocardium and protect it from injuries during the following recovery of physiological Ca2+ content in the extracellular medium. PMID- 1286685 TI - [The topological characteristics of rat myocardial reactivity to noradrenaline, acetylcholine and a change in the electrostimulation frequency]. AB - Dose-dependent effects of noradrenaline (10-7-10-6M), acetylcholine (10-8-3x10 6M) and stimulation rate (0.2-2.0 Hz) were obtained in experiments on myocardium preparations of the right and left atria and ventricles in rat. Three types of topological differences of the rat myocardium reactivity were observed: between the atria and ventricles (A/V), between the right and left atria and ventricles (R/L), between the right atrium (RA) and other cardiac chambers. A/V differences were most pronounced in the reactivity to acetylcholine (the atria were more reactive), the highest R/L differences were observed in the reactivity to noradrenaline (the myocardium of the right chambers was more reactive). RA reactivity greatly exceeded reactivity of other myocardial preparations to all three test influences. Topological peculiarities of chrono-inotropism permit supposing, that inotropic effects of rate changes in vivo are able to compensate, to some extent, the regional nonuniformity of cholin- and adrenergic regulatory inotropic effects. PMID- 1286686 TI - [The anticonvulsive action of the intranigral administration of the delta sleep inducing peptide]. AB - It is shown that injection of delta sleep-inducing peptide (DSIP) into the substantia nigra reticular part (SNrp) suppresses generalized convulsive activity induced in rats by picrotoxin and corazol injection but exerts no influence on the strichnine-induced seizures. The analogous DSIP injection causes the antiepileptic action in rats kindled through picrotoxin injections. The DSIP intranigral anticonvulsant action is blocked by naloxon and enhanced by haloperidol and yohimbin. It can be concluded that DSIP anticonvulsant action may be realized due to activation of SNrp-dependent opioid mechanisms and suppression of dopaminergic ones. PMID- 1286687 TI - [The mechanisms of the formation of cardiogenic afferent effects after the development of local immune damage to the heart]. AB - Sensitivity of cardiac receptors to several substances after local immune heart damage and the nature of cardiogenic influences on the circulation were studied in acute experiments o anesthetized dogs. The depressor reflexes from the heart were shown to disappear during 30 min. after immune heart damage, and vagal afferent impulse activity decreased. After immune heart damage, cardiac sympathetic afferent fibres were more sensitive to endogenous biological substances than to vagal ones. The sympathetic cardiac afferent system is found to be more sensitive to chemical agents, which is a decisive factor in formation of cardiogenic influences on the circulation during pathological processes in the heart. PMID- 1286688 TI - [The effect of different gas mixtures under increased pressure on the self stimulation reaction of rabbits]. AB - Self-stimulation of rabbits in heliox at high pressure was decreased. That effect was potentiated by rapid compression. Addition of 2% or 6% nitrogen to heliox exerted no influence on the self-stimulation behavior. PMID- 1286689 TI - [Seasonal changes in the functional characteristics of the thrombocytes in inhabitants of the territories of Ukraine and Cuba]. PMID- 1286690 TI - [The central mechanism of the immunomodulating action of vasopressin and its structural analogs]. AB - It is shown that the effect of neuropeptides depends on the dose and their structure. Considerable immunostimulation is observed after administration of [8 arginine]vasopressin and des-9-glucine-[8-arginine]vasopressin as against the control. This stimulation is prevented by the preliminary heloperidol blockade of dopaminergic receptors, i.e. it is dopamine-dependent. At the same time, injection of tetrapeptide vesopressin-(2-5) induces deep immunosuppression in all the applied doses. The peptide immunosuppression is shown to be a result of interaction with another neuromediator (serotoninergic); it has no effect under preliminary cuproheptadine blockade of C-2 serotonin postsynaptic receptors. The immunomodulating effect of the neuropeptides studied is central one and is realized via the hypothalamus-hypophysis complex. PMID- 1286691 TI - [An analysis of the mechanism of the effect of intragastric calcium and magnesium on the release of gastrin and insulin in dogs]. AB - The experiments have been carried out on four intact awake dogs to study the influence of intragastric introduction of deionized water, 5 mmol/l of calcium and magnesium chloride solutions in a dose of 3 ml/kg on release of gastrin and insulin into blood. It is stated that during the first 4 min after infusion of deionized water the release of gastrin decreases by 89 +/- 32 conventional units (c.u.), CaCl2 exerts a more pronounced inhibitory effect (168 +/- 36 c.u.), while MgCl2, on the contrary, increases the gastrin release by 398 +/- 92 c.u. Atropin (0.03 mg/kg, subcutaneous injection, 10 min before infusion) absolutely takes away the gastrin-stimulating effect of magnesium, but it has almost no influence on the gastrin-inhibitory effect of calcium. The latter can be taken away by 62% by ornid (5 mg/kg subcutaneously, 20 min before infusion). Preliminary anaesthesia of the stomach mucosa by trymecain or novocain absolutely remove the effect of both calcium and magnesium. Insulin release remained significantly unchanged in any series of experiments. PMID- 1286692 TI - [The ultrastructural changes in the glomeruli and juxtaglomerular apparatus at different periods of endotoxic shock]. AB - It is shown that after endotoxin injection the ultrastructural changes in the glomeruli can favour development of the acute renal insufficiency. In the initial and intermediate periods of the endotoxin shock the granular and agranular forms of juxtaglomerular cells hyperfunction, respectively, are revealed as well as an increase of renin activity in plasma. At the stage of the late endotoxemia ultrastructural alterations are stabilized. The juxtaglomerular cells synthesize and accumulate secretory granules, but renin activity in plasma decreases almost to the initial level. PMID- 1286693 TI - [The effect of long-term bed-rest head-down-tilt hypokinesia on the functional properties of the human neuromuscular apparatus]. AB - An influence of 120-days antiorthostatic (-6 degrees) hypokinesia (ANOH) on the functional properties of human m. triceps surae (TS) was investigated. After ANOH the maximal force and the maximal voluntary contraction of TS decreased on the average by 45.5% and 33.7%, respectively, and the maximal twitch response force- by 36.7% (P < 0.05-0.01). The value of force deficit increased on the average by 60.2% (P < 0.001), while a relative increase of the TS force contraction decreased in response to pair irritation (P < 0.05-0.01) as well as the velocity properties of TS after ANOH (P < 0.05-0.001). The rate of absolute (c.u.) tension development fell significantly in response to electrical nerve irritation and during voluntary contraction, while the force-velocity muscle properties according to relative (%) parameters remained unchanged. The fatiguability index of TS constituted the average 0.61 +/- 0.02 after ANOH as against 0.80 +/- 0.03 prior to it (P < 0.05). It is postulated the alterations of contractile properties of TS are due both to atrophic processes, muscle length change, condition of sarcoplasmic reticulum and to changes in the state of the central nervous system. PMID- 1286694 TI - [The dynamic accumulation of a low-molecular physiologically active depressor factor and its biological effects in hemorrhagic shock]. AB - A low-molecular factor (800-1000 D) was isolated from the blood serum of dogs using selective ultrafiltration. That factor was taken in various terms of the hemorrhagic shock development. Biological activity of the factor was determined in experiments on isolated hearts of dogs and lymphoid cells. It is found that the above factor decreases the contractile function of the isolated heart, disturbs energy formation, inhibits the antibody-forming function of the spleen as well as possesses a cytolytic effect on lymphocytes of the peripheral blood lympho-nodes and thymus. PMID- 1286695 TI - [An analysis of the scientific publications of the A. A. Bogomolets Institute of Physiology of the Academy of Sciences of Ukraine]. AB - Scientific publications from three sectors of the Institute have analyzed for the period since 1979 till 1988 inclusive. The analysis is based on data of annual reference books Science Citation Index (SCI) and lists of publications of each researcher of the Institute. It is shown that with almost equal numerical strength of researchers and similar number of publications the sector of molecular physiology contributed 43.6% to cited works 48.2% of these works are included into database of SCI. Such indices for the sectors of neurophysiology and physiology of visceral systems accounted for 33%, 33.4% and 23.4, 18.4% respectively. It is of interest that 47.5% of references to the cited works of the molecular physiology sector were made by foreign scientists and self-citation constituted 17.4%, while for the other sectors such indices had a reverse relationship. The problem on objectification of estimation of research is under discussion. PMID- 1286696 TI - [The action of specific antimembrane antibodies on the tonic tension and contractile phases of the heart muscle in rats]. AB - Antibodies specific to rat myocardial sarcolemma inhibit phasic contractions and promote an increase in tonic tension of isolated strips of the cardiac muscle in rat. These results indicate that antibodies induce accumulation of intracellular free Ca2+. Analysis of the authors' data and those from literature suggests that specific antibodies inhibit Na(+)-K(+)-pump activity of the cardiac muscle in rat. This conclusion is confirmed by analogy of effects of ouabaine, the well known inhibitor of Na(+)-K(+)-pump, on the rat cardiac muscle. PMID- 1286698 TI - [The effect of an electromagnetic field on the indices of conditioned reflex activities in rats]. AB - The formation of defensive conditional reflexes in rats exposed to 10 cm electromagnetic field of different power densities during 4-months-long experiment has been studied. Stability of conditional reflectory reactions for the whole period of exposure is shown. The after-exposure period is characterized by the prevalence of excitatory processes. PMID- 1286697 TI - [The prevention of the development of myocardial contracture in the "calcium paradox" by action on Na-Ca metabolism]. AB - The effect of artificial high sodium gradient on the rate of the myocardium contracture development during "calcium paradox" was studied in the experiments on the isolated heart of Langendorf-perfused rats. It is stated that artificial creation of a high sodium gradient decreases the rate of the myocardium contracture development. Exogenous nucleotides, activators of Na, K-ATPase, and their precursors intensified the protective action of the hypersodium medium. Phosphocreatine (100 mmol/l) had no protective effect during the "calcium paradox". However, under conditions of the high sodium gradient phosphocreatine efficiently prevented development of the contracture during the "calcium paradox". It is important to note that under analogous conditions creation of high osmosity of the solution adding 12 mmol/l of saccharose does not protect the heart from development of the myocardium contracture. PMID- 1286699 TI - [A new method for cannulation of the common bile duct in an experiment]. AB - The proposed method of common biliary duct cannulation is simple, easily performed and permits studying bile hydrodynamics biligenesis for a necessary time. Tightness of the system is completely preserved after removal a choledochostomical tube. Walls of the invaginated stump of the cystic duct are swiftly abated as a result of hydrostatic pressure and cover its gap. The presence of purse string kapron suture in a stump orifice creates an obstacle to deinvagination. Good reparation properties of serous and subserous membranes, covering the biliary duct, promote rapid closing of stoma. Effectiveness of the proposed method of common biliary duct cannulation by means of the invaginated stump of the cystic duct is confirmed by the smooth postoperative course and absence of a biliary fistula after the tube removal. PMID- 1286700 TI - [The hordox correction of excessive proteolytic activity and the sialic acid content of the blood under an emotional influence on rabbits]. AB - The influence of the acute emotional stress on the activity of proteolysis and content of free sialic acids in the blood under usual conditions and after the preliminary introduction of gordox has been studied in the experiment on rabbits. It is established that the parallel rise of their levels under stress reflects degradation of glycoproteins and fragments containing sialic acids under the influence of the increased activity of proteinases. Gordox, together with the inhibition of excessive activation of proteolysis, prevents the rise of the level of sialic acids under the influence of the stress action. The conclusion is made that it is expedient to use inhibitors of proteolytic enzymes for prevention of cellular lesions in stress. PMID- 1286701 TI - Would taming the T-cell quieten the eye? PMID- 1286702 TI - Duke-Elder Lecture: new concepts on the role of autoimmunity in the pathogenesis of uveitis. PMID- 1286703 TI - The effect of retinal autoantigens and their peptides on the inhibition of experimental autoimmune uveitis. AB - Experimental autoimmune uveitis is an immune-mediated inflammation of the retina and uveal tract. Such inflammation can be induced in eyes of experimental animals by inoculating them with retinal autoantigens. This animal model of uveitis closely resembles idiopathic uveitis in humans and lends itself ideally for the study of mechanisms involved in the aetiopathogenesis of uveitis and for the evaluation of methods used to control or prevent immune-mediated intraocular inflammation. In this study we used the retinal proteins S-antigen, interphotoreceptor retinoid binding protein and some synthetic peptides of S antigen to modulate the immune response of Lewis rats. Following immunomodulation these animals did not develop uveitis when challenged with the retinal proteins. The discovery of small, non-pathogenic peptides of retinal antigens that down regulate the immune response has relevance in developing strategies for immune intervention in human uveitis. PMID- 1286704 TI - Sympathetic ophthalmia: visual results with modern immunosuppressive therapy. AB - Sympathetic ophthalmia is a rare bilateral panuveitis that follows penetrating injury to one eye. The use of systemic corticosteroids has transformed the prognosis, and good acuity in the sympathizing eye can now be achieved. The use of immunosuppressive drugs, such as cyclosporin and azathioprine, in combination with the steroids, allows control of the intraocular inflammation at a much lower steroid dose, with concomitant reduction in the systemic side effects that accompany the use of systemic steroids. PMID- 1286705 TI - Passing the DVLC field regulations following bilateral pan-retinal photocoagulation in diabetics. AB - Twenty-one diabetics who had had bilateral retinal panphotocoagulation preserving a visual acuity sufficient to pass the Driver and Vehicle Licensing Centre (DVLC) requirements were assessed with regard to their ability to satisfy the DVLC visual field requirements. Of the 19 patients treated with the laser alone, 17 met the requirements for a licence to drive a private vehicle. The use of the Xenon photocoagulator and large total burn area following laser was found to be associated with an increased risk of DVLC field test failure. Adequate PRP with 200 micron burns appeared to induce neovascular regression and be compatible with passing the DVLC field regulations in many patients. Panphotocoagulation of patients with early proliferative retinopathy using 200 micron burns does not appear to jeopardise a driving licence. Guidelines for laser treatment in diabetic retinopathy aimed at preserving the driving field are presented. PMID- 1286706 TI - Spontaneous relieving retinotomies in diabetic silicone filled eyes. AB - We describe in six patients the delayed occurrence of inferior tractional retinal detachments following epiretinal reproliferation 4 to 5 months after vitrectomy and silicone oil tamponade for diabetic related retinal detachments. The epiretinal traction was spontaneously relieved by the occurrence of large inferior tension breaks which subsequently enlarged and coalesced to form retinotomies. This process appears to be relatively benign as it remains limited to the peripheral retina, and in all six patients the posterior retina has remained attached for a minimum of 12 months follow up, with improved central visual acuity. PMID- 1286707 TI - Criteria for intravitreal antibiotics during surgical removal of intraocular foreign bodies. AB - Published opinion supports the early use of prophylactic antibiotics soon after presentation of a potentially contaminated intraocular foreign body (IOFB) in the posterior segment, preferably within 12 hours of trauma when the visual acuity is still good. Recommended treatment includes topical, subconjunctival, parenteral and especially intravitreal antibiotic therapy to reduce the chance of endophthalmitis. Intravitreal therapy should include gentamicin with vancomycin or clindamycin to cover Bacillus spp., since this organism is responsible for half the endophthalmitis cases and produces beta-lactamase giving resistance to penicillins and cephalosporins. Intravitreal therapy is important because systemic and topical antibiotics do not penetrate the globe in sufficient concentration to control a fulminant infection associated with damaged tissue. Early therapy is essential, as delaying treatment until endophthalmitis occurs is less likely to save useful vision. All vitreous aspirated, plus pus if present, and the IOFB should be cultured for bacteria and fungi to identify pathogens and gain antibiotic sensitivities. The prevention of IOFB-associated endophthalmitis requires early recognition of the IOFB and enthusiastic antibiotic therapy at the time of its removal. PMID- 1286708 TI - Aqueous kinetics of sisomicin sulphate. AB - Sisomicin sulphate is a new-generation aminoglycoside with a broad spectrum of antimicrobial activity that includes Pseudomonas aeruginosa. It is superior to gentamicin against indole-negative Proteus and some resistant strains of Pseudomonas. The ocular pharmacokinetics of sisomicin have not been explored. We used the agar diffusion technique of microbial assay to determine the aqueous penetration and bioavailability of a subconjunctivally placed standard dose of 20 mg/0.4 ml of sisomicin sulphate in 20 human volunteers undergoing elective cataract surgery. A peak concentration of 16.4 mg/l was found in the aqueous humour 78 minutes after injection, which is 65 times the minimum inhibitory concentration for Pseudomonas. The antibiotic was bioavailable up to 1203 minutes after injection in a concentration of 0.9 mg/l, which easily covers the minimum inhibitory concentration of Staphylococcus aureus and Pseudomonas. The antibiotic disappears from the aqueous humour at the 1434 minute interval (approximately 24 hours). The elimination half-life (t1/2 of sisomicin was determined to be 5.16 hours (K = 0.134/hour) and the aqueous clearance was 2.87 microliters/min. PMID- 1286709 TI - Stereopsis and ageing. AB - This study reports the prevalence of defective stereopsis in an elderly population. Of 728 individuals over the age of 65 who attempted a Frisby stereotest, only 27% had full stereopsis and 29% had no stereopsis. In the elderly population defective stereopsis is a common finding in the absence of any other ocular morbidity. The prevalence of defective stereopsis increased with age. This finding was noted as a part of a survey of eye health of elderly people living in an inner city. The finding was not associated with any symptoms. The significance of this finding is discussed. PMID- 1286710 TI - Retinopathy of prematurity: a prospective study. Review at six months. AB - A cohort of infants of birthweight < or = 1700 g studied prospectively for retinopathy of prematurity (ROP) has been reviewed at 6 months corrected age and the findings related to the neonatal data. The overall incidence of strabismus was 6.4% (30/468), rising from 3.1% (7/229) without ROP to 29.2% (7/24) with stage 3. Strabismus and fusional ability were significantly related to presence and severity of ROP, and abnormal neonatal cranial ultrasound findings. Binocular visual acuity was measured in 340 infants between 20 and 40 weeks corrected age. Eight were subnormal, all due to neurological problems. For the remainder, despite falling within the normal range, there was a significant trend (p < 0.001) for lower acuities with increasing ROP severity. Cycloplegic refraction on 387 infants revealed, with increasing ROP severity: 1, a significant trend towards myopia; 2, increased magnitude of astigmatism; 3, alteration of the astigmatic axis; 4, increased incidence of anisometropia. For the first three categories there was an insignificant trend between no ROP and stage 2, reaching significance only between stage 2 and 3. The predominant axis of astigmatism in infants without ROP was between 60 degrees and 120 degrees, but with ROP there was a significant trend away from this direction. PMID- 1286711 TI - The mersilene covered intraorbital implant. AB - The most widely used material for covering spherical intraorbital implants is sclera. Mersilene mesh is an alternative substance combining the advantages of permanent implant cover with low rates of infection and ready availability. We describe our experiences in the use of Mersilene mesh covered intraorbital implants in 14 patients. Our findings suggest that Mersilene mesh could be considered as a possible alternative choice of material for covering intraorbital implants. PMID- 1286712 TI - The National Cataract Surgery Survey: I. Method and descriptive features. AB - The National Cataract Surgery Survey is a prospective cross-sectional survey of surgery for age-related cataract within the National Health Service. It is the first national study of cataract surgery in the United Kingdom providing clinical data. This is the first in a series of papers and describes a profile of the characteristics of patients admitted for cataract surgery that includes: demography, referral sources, presence of co-existing ocular pathology, level of visual impairment on admission and waiting time for surgery. A profile of the process of the surgical procedure for 1990 is also described: number of operations performed, type of admission, type of anaesthetic, cataract extraction and intraocular lens and the grade of surgeon performing the procedure. PMID- 1286713 TI - Results of intraocular lens implantation in paediatric aphakia. AB - Intraocular lenses were implanted in 16 eyes of 13 patients with congenital cataract, and visual progress was plotted using a preferential-looking technique. Initial surgery was by lens aspiration with preservation of the posterior capsule, and subsequent posterior capsulotomy without anterior vitrectomy. Poly HEMA posterior chamber lenses were used, usually as a primary procedure but in four cases as a secondary procedure after contact lens failure. No serious complications were encountered. Most eyes achieved a very significant visual improvement, and none were worse than preoperatively. Residual refractive error was highly unpredictable, but did not exceed 6 dioptres. The importance of rigorous occlusion therapy is stressed. With close follow-up, this procedure offers an effective and safe method for the correction of unilateral paediatric aphakia, and, in selected cases only, for bilateral aphakia. PMID- 1286714 TI - The newer generation intraocular lens power calculation formulae in anterior chamber implants. AB - One hundred and fifty-one eyes with anterior chamber implants and a best corrected visual acuity of at least 6/12 were studied to compare the predictive accuracies of the newer generation intraocular lens power calculation formulae. There was no statistically significant difference between the predictive accuracies of the SRK (Sanders-Retzlaff-Kraff), SRK II, SRK/Theoretical (SRK/T) and Holladay formulae. All these four formulae were more accurate than the Binkhorst II formula. PMID- 1286715 TI - Peripheral corneal oedema following cataract extraction (Brown-McLean syndrome). AB - We describe the clinical features of 21 eyes of 15 patients who developed peripheral bullous corneal oedema following cataract extraction. The peripheral oedema was asymptomatic in all cases and was only noted at a review examination. Although the onset of the peripheral oedema was probably delayed for several years after surgery, it was not documented to progress in any patient or to involve the central cornea. Endothelial specular microscopy did not reveal any endothelial features that are specific for this condition, but confirmed that the central endothelial cell density can be as high as 2150 cells/mm2 in the presence of peripheral corneal decompensation. Despite the surface irregularity resulting from the peripheral corneal oedema 12 patients (18 eyes) continued to wear contact lenses to correct their aphakia. PMID- 1286716 TI - Suitability for day case cataract surgery. AB - Areas of concern about day case surgery are highlighted. A group of 442 patients underwent cataract surgery with lens implant. They were randomly allocated to day case or inpatient groups. Questionnaires were used to assess opinions about day case cataract surgery and how patients felt they would manage. None of the areas of concern were actually a problem. Difficulties encountered by patients and clinicians in the postoperative period are discussed. Most patients appear suitable for day case surgery provided they are well informed. PMID- 1286717 TI - The effect of electromagnetic stimulation of the posterior parietal cortex on eye movements. AB - The posterior parietal cortex probably plays a central role in the sensorimotor transformations needed to make an accurate saccadic eye movement to a visual target. In an attempt to disrupt the normal programming of saccades, we magnetically stimulated the posterior parietal cortex in human volunteers, 80 ms after a small target moved 5 degrees horizontally from the centre of a VDU screen. Saccadic eye movements were recorded and experimental trials were compared with control, unstimulated trials. Magnetic stimulation was triggered in 70% of the trials selected randomly. The main effects of stimulation were: increased divergence of the eyes before each saccade, greater latency of saccade onset, and a tendency to undershoot the target. These results support the hypothesis that the posterior parietal cortex is involved in the programming of accurate saccades to visual targets. PMID- 1286718 TI - Hypertropia following insertion of inferiorly sited double-plate Molteno tubes. AB - The use of double-plate Molteno tubes is well established in the management of intractable glaucoma, particularly in eyes that may have had previous surgical procedures, often involving the superior conjunctiva with subsequent subconjunctival scarring. As it is frequently the case that the area of least scarring is inferiorly, we have sited the tubes there but have found that, although this usually provides good control of intraocular pressure, successful drainage of aqueous has been associated with the development of hypertropia due to upward displacement of the globe by fluid encapsulated around the plates. We report a retrospective study of 16 eyes undergoing inferiorly sited double-plate Molteno tubes, in which 9 eyes developed significant hypertropia at a mean time after insertion of 3.5 months. Mean degree of hypertropia was 9.8 prism dioptres. The management of this complication is discussed. PMID- 1286719 TI - A comparison of the OKP visual field screening test with the Humphrey field analyser. AB - In order to determine the loss of retinal sensitivity detectable by oculokinetic perimetry (OKP), we tested 27 eyes of 27 persons with glaucoma and 32 eyes of 32 patients with ocular hypertension with the OKP screener and with a central threshold test on the Humphrey analyser. The threshold at eight locations on the OKP chart between 12.5 degrees and 15 degrees from fixation was compared with the corresponding Humphrey perimetric thresholds. Seventeen eyes from 17 patients with glaucoma failed the OKP screening test by not seeing the target at one or more locations. The mean light sensitivity threshold at points seen on OKP screening was -5.8 dB (SD 4.6 dB) from aged-matched normals (AMN), whereas points missed had a mean threshold -16.1 dB (SD 9.3 dB) from AMN. The sensitivity and specificity with which OKP testing differentiated normal points from abnormal ones in Humphrey testing was 82.5% and 80% respectively, with a threshold criterion of -12 dB from AMN. Ten eyes from 10 patients with glaucomatous defects and all of the ocular hypertensive eyes gave normal responses on the OKP screening test. The glaucomatous eyes that passed were characterized by less severe defects on the Humphrey than those who failed in terms of mean deviation (0.02 < p < 0.05) or corrected pattern standard deviation (0.01 < p < 0.02). Four of the glaucomatous eyes to pass had a nasal step as the primary field defect. None of those to fail failed only on points within 10 degrees of fixation. We suggest further modification of the OKP screening chart to improve its efficiency. PMID- 1286721 TI - Deterioration in the accuracy of the pulsair non-contact tonometer with use: need for regular calibration. AB - The Pulsair non-contact tonometer (Keeler Pulsair: Keeler UK) has been shown to be a versatile instrument particularly suitable for screening for raised intraocular pressure. Although demonstrated to be accurate initially when compared to the Goldmann applanation tonometer no study has examined its long term accuracy. Comparisons of three Pulsair tonometers with different degrees of usage with the Goldmann tonometer are described. Measurements were obtained from 64, 116, and 223 eyes in three separate comparative studies. Correlation coefficients of between 0.78 and 0.90 were obtained, the least used instrument being significantly more accurate than the two more extensively used instruments. Taking the Goldmann tonometer as the standard tonometer, and the aim to detect intraocular pressures of greater than 21 mmHg, sensitivities of 40%, 48%, and 85% for the three Pulsair tonometers respectively were shown. The Pulsair tonometer appears liable to a long-term drift in accuracy with use, and we suggest that provision is made for the regular re-calibration of the instrument. PMID- 1286720 TI - Sezolamide: additivity to timolol twice daily. AB - Sezolamide, a potent topical carbonic anhydrase inhibitor previously known as MK 417, was studied to determine its ocular hypotensive activity in patients with elevated intraocular pressure while on continuing therapy with topical timolol. This was a three-centre, double-masked, randomised, placebo-controlled, parallel study in 36 patients with bilateral primary open angle glaucoma or ocular hypertension on therapy receiving 0.5% timolol twice daily, with a morning intraocular pressure greater than or equal to 22 mmHg in both eyes 2-4 hours following an 8 a.m. dose of timolol. Sezolamide 1.8% or placebo twice daily was added to treatment with timolol on the evening of day 1 and continued for 2 weeks. Twelve-hour diurnal curves were performed before the study on day 1 (timolol alone) and on day 15. Intraocular pressure measurements were also taken on days 2 and 8 at 8 a.m. and 9 a.m. Patients who received timolol and sezolamide showed additional intraocular pressure reductions from day 1 (timolol alone) of 8.0 to 15.5%, which were significant at all times. At hours 1, 2, 4 and 8 the reductions in intraocular pressure observed in the group receiving sezolamide and timolol were significantly greater than those in the group receiving timolol and placebo. PMID- 1286722 TI - Living with a scanning laser ophthalmoscope. PMID- 1286723 TI - Management of orbital cellulitis. PMID- 1286725 TI - Effect of constant magnetic field on the liver of guinea pig. Electron microscopic studies. AB - Twenty guinea pigs were exposed 1 hour daily, for 3 to 7 weeks to constant magnetic field (CMF), the induction of which was 0.005 T, and 0.3 T. Hepatocytes were examined in semithin sections with light microscope and TEM. The negative photographic plates of the TEM were analyzed and measured with densitometer. It was shown that CMF of the induction 0.005 T and 0.3 T exhibited structural changes in hepatocytes, primarily in mitochondria. PMID- 1286724 TI - Neurotoxic effect of vincristine on ultrastructure of hypothalamus in rabbits. AB - The neurotoxic side-effects are a striking accompaniment of the therapy with vincristine (VCR). Data concerning the influence of VCR on the central nervous system are controversial. In the present study a schedule of VCR treatment was employed to develop the neurotoxic side effects in New Zealand rabbits. In all treated animals neurons were primarily and most severely affected cells. Most of them underwent degeneration. The consecutive stages of the increasing condensation of chromatin and cytoplasm of these cells were observed. Degeneration of the synaptic connections and secondary changes in myelin sheaths of degenerating axons were found. Debris of some death cells were localized intracellularly or as typical apoptotic bodies ingested by some glial cells. Astroglia underwent swelling and their processes separated dying neurons from the surroundings. All the results lead to conclusion that the VCR treatment concomitant with neurotoxic symptoms may affects regions of CNS lacking of blood brain barrier. Neurons are most vulnerable cells of the brain parenchyma. The changes induced in neurons by the drug are characteristic in many aspects to those described in many cells undergoing apoptosis. PMID- 1286726 TI - The monoclonal antibody (MAB) CD 68 allows the immunocytochemical identification of macrophages in primary and metastatic brain tumors in paraffin embedded tissues. AB - While using the MAB CD 68 applied to paraffin embedded tissue specimen, macrophages could be marked in 31 primary brain tumors of glial origin and in 17 metastatic tumors from which 7 were carcinomas of the lung, 5 carcinomas of the breast, 2 from the digestive tract and 3 were clear cell carcinomas of the kidney. Despite quantitative differences between the primary and metastatic tumors in all specimen examined macrophages were found. The macrophages were localized within the tumor tissue, at the periphery of the tumor and its surroundings. In some cases cells with an intensive staining reactions were visible in blood vessel walls. No correlation between the type of tumor and intensity of macrophages infiltration has been found, however there were quantitative differences between primary and metastatic tumors. PMID- 1286727 TI - Genetic changes in Morris hepatoma 7777 cells. AB - Analysis of genetic changes in Morris hepatoma 7777 is described. Three different approaches were applied: DNA and chromosome transfection, karyotype analysis, and Southern hybridization modified by use of PFGE. Changes in the genome of tested cells were identified by PFGE and chromosome transfection. This supports the statement that PFGE is a useful method in transformed cell genome analysis. PMID- 1286728 TI - A model of Ph' positive chronic myeloid leukemia-blast crisis cell line growth in immunodeficient SCID mice. AB - A human Philadelphia-chromosome positive chronic myeloid leukemia-blast crisis (CML-BC) cell line BV173 proliferated in the hematopoietic tissues, infiltrated various organs and caused the death of immunodeficient SCID mice. Leukemia spreading was assessed with diminished number of bone marrow cells and caused splenomegaly. The leukemic colonies grew from single cell suspension of bone marrow, spleen and peripheral blood. Bcr-abl m-RNA was detectable in bone marrow, spleen, peripheral blood, liver, lungs and brain. Dying mice demonstrated severely hypoplastic bone marrow, splenomegaly and massive metastases in the liver and kidneys. The survival time of animals was dependent on the number of inoculated leukemia cells. PMID- 1286729 TI - Anchorage-dependent growth factor(s) produced by rat sarcoma (XC) cells. AB - The autocrine growth factor(s) was isolated from serumfree conditioned medium of rat sarcoma (XC) cells. Autocrine activity was enriched by ultrafiltration using Amicon YM 10 membrane, extraction with 1 M acetic acid and partially purified (650-fold) by chromatography on Bio-Gel P-100 and P-60. The final recovery of the autocrine factor(s) was 4 micrograms from 1800 ml of the conditioned medium (a yield of 6%). The factor(s) with molecular weight 6-10 kDa was heat and acid stable but inactivated by trypsin and dithiothreitol. It stimulated anchorage dependent (but not anchorage-independent) growth of XC cells as well as untransformed, established lines of rat (NRK) and mouse (3T3) cells. The results obtained may suggest that autocrine factor(s) produced by XC cells can be one of EGF-like or/and insulin-like growth factors. PMID- 1286730 TI - Malaria in the WHO Southeast Asia region. PMID- 1286731 TI - Selection of permethrin resistance in the malaria vector Anopheles stephensi. AB - The laboratory strain of Anopheles stephensi, a well-known urban malaria vector, was selected with permethrin, a synthetic pyrethroid at LD90 level up to five generations. The selection resulted in the development of resistance in F5 generation to the tune of 13-fold to permethrin and cross-resistance to the tune of 7-fold to cypermethrin, 9-fold to alphamethrin, and 10-fold to deltamethrin. The development of cross-resistance to 4% DDT was also noticed. The susceptibility status against 5% malathion was maintained throughout the five generations. The synergistic effect of piperonyl butoxide with permethrin did not overcome the development of resistance. The development of resistance showed a significant relationship between hatchability and different generations. PMID- 1286732 TI - Hepatic changes in P. falciparum malaria. AB - Liver function tests were performed in 165 hospitalized patients suffering from P. falciparum malaria with complications. Serum bilirubin was found increased in 33 patients, and 22 of them had unconjugated hyperbilirubinaemia. Serum alanine aminotransferase was increased in 5 patients, but only to mild to moderate levels. Serum alkaline phosphatase was increased in 11 patients, gamma-glutamyl transpeptidase in 3 patients. Serum total protein and albumin were significantly decreased but these were considered more as indicator of acute phase response. Liver cell necrosis was observed in one patient, and oedema and mononuclear cell infiltration in two patients. Though hepatomegaly and mild elevation of enzymes can be observed in a significant proportion of patients, involvement of liver leading to acute hepatitis or liver cell necrosis is a relatively uncommon complication in P. falciparum malaria. PMID- 1286733 TI - A longitudinal study to monitor chloroquine-resistant P. falciparum malaria in Bokajan and Manja PHC areas of Karbi Anglong District, Assam. AB - In-vivo as well as in-vitro studies were carried out at regular intervals from 1979 to 1988 to monitor chloroquine resistance in P. falciparum in Bokajan and Manja PHC of Karbi Anglong district, Assam. The results showed no significant change in resistance status in the area. Intensified antivector measures, withdrawal of chloroquine pressure and prompt detection and treatment of P. falciparum cases with alternative drugs helped bring down the higher grades of resistant parasites by 1984, which however could not be maintained. The results of in-vitro tests correlated well with those of in-vivo tests. The Karbis seemed to have better immunity against the strain of P. falciparum than the non-Karbis residing in the area. However, there was no difference in the rate of sensitive and resistant cases detected amongst the two groups. PMID- 1286734 TI - Matrix based approach for identification of Indian anophelines. PMID- 1286735 TI - Breeding habits of Anopheles stephensi Liston in an area of Calcutta. PMID- 1286736 TI - Report of three cases of P. falciparum showing moderately high parasitaemia. PMID- 1286737 TI - Decisions for Norplant programs. PMID- 1286738 TI - A comparative study of a new food supplement, ViviScal, with fish extract for the treatment of hereditary androgenic alopecia in young males. AB - A controlled, randomized, double-blind, parallel-group study compared the effects of ViviScal (a new food supplement incorporating special marine extracts and a silica compound) with those of a fish extract in the treatment of young males with hereditary androgenic alopecia. The pretreatment histological diagnosis was alopecia with a mild to moderate perifollicular inflammation zone. The study consisted of 20 subjects who received two tablets of ViviScal once daily and 20 who received two tablets of fish extract once daily for 6 months. The mean patient age and mean duration and severity of baldness compared well between the two groups. Most patients had been treated with long-term topical 2% minoxidil for 1 year or more prior to the study. At baseline and after 6 months' treatment, a biopsy was taken for histological examination. A non-vellus hair count was performed at baseline and after 2, 4 and 6 months. In the fish extract treatment group three patients withdrew from the study before the fourth month due to lack of therapeutic effect. After 6 months' treatment, patients receiving ViviScal showed a mean increase in non-vellus hair of 38% compared with a 2% increase in the fish extract treatment group (P < 0.0001). In the ViviScal group, 19 (95%) subjects showed both clinical and histological cure, whereas none treated with fish extract showed any clinical or histological difference after 6 months' treatment (P < 0.0001). In both groups, a minimal decrease in the erythemal index was observed. In conclusion, ViviScal appears to be the first highly active treatment for androgenic alopecia in young males. PMID- 1286739 TI - The effect of a single oral morning dose of nizatidine and ranitidine on intragastric pH under basal conditions and after pentagastrin stimulation. AB - A comparison was made of the antisecretory activity of orally administered nizatidine and ranitidine by measuring intragastric pH under basal conditions and during and after pentagastrin stimulation. Intragastric pH values were measured with a bipolar glass electrode in 10 patients with healed duodenal ulcers treated with nizatidine or ranitidine according to a randomized single-blind design. The antisecretory activity of the two drugs was similar during the 4 h of monitoring following drug administration. Nizatidine, however, showed a more rapid inhibitory action than ranitidine, producing a significantly greater increase in pH with respect to basal values during pentagastrin infusion. In the period following infusion the pH values observed with ranitidine were higher than with nizatidine, but not significantly so. Under these experimental conditions, therefore, the antisecretory activity of nizatidine was shown to be more rapid than that of ranitidine and equally effective. PMID- 1286740 TI - In vitro evaluation of plasticizer activity on the growth and metabolism of chick embryo fibroblasts and on the development of chick embryo lungs. AB - Administration of di(2-ethylhexyl) phthalate (DEHP) to primary cultures of chick embryo fibroblasts brought about a decrease in cell proliferation rate after 48 h and an inhibition of both DNA and protein synthesis measured by [3H]thymidine and [3H]leucine, respectively, after 48 h. The growth of chick embryo lung rudiments in vitro was also depressed by DEHP treatment. Lung rudiment were smaller in DEHP treated embryos after 6 days' treatment. These results indicate that DEHP has a cytostatic effect on embryonic cells and tissues. PMID- 1286741 TI - Effects of nicergoline on calcium and magnesium deposition in the central nervous system tissues of rats maintained on low-calcium diets. AB - Reduction of calcium intake leads to the mobilization of calcium and magnesium from the bone pool and to calcium deposition in the soft tissues, especially in the central nervous system (CNS). The effects of 10 alpha-methoxy-1,6 dimethylergoline-8 beta-methanol 5-bromonicotinate (nicergoline), an ameliorator of cerebral circulation and metabolism, on the deposition of calcium and magnesium in the CNS, heart, liver, kidney, muscle, abdominal aorta and bones were studied in rats maintained on standard and low-calcium diets. Rats were fed the following diets for 90 days: standard calcium (12.5 g/kg); standard calcium with 60 mg/kg nicergoline; low-calcium (30 mg/kg); and low-calcium with 60 mg/kg nicergoline. The presence of nicergoline did not affect blood chemistry but magnesium concentrations in the liver were significantly (P < 0.05) higher in rats fed standard diet with nicergoline. Magnesium concentrations in the occipital cortex, pons, cerebellum, liver, kidney, muscle and femur of nicergoline-treated rats fed low-calcium diet were significantly (P < 0.01-0.05) higher compared with those in the corresponding controls, whereas the calcium concentrations in the femur of nicergoline-treated rats fed both standard and low calcium diets were significantly (P < 0.05) higher than those in the corresponding controls. In general, nicergoline tended to preserve the calcium content in the bone of rats fed a standard diet. Nicergoline may be implicated in calcium metabolism in rats fed low-calcium diets and may activate cerebral metabolism through the maintenance of magnesium concentrations in the CNS and soft tissues. PMID- 1286742 TI - Agranulocytosis during treatment with fluconazole. AB - Fluconazole, a new effective triazole antifungal agent, has been reported to cause fewer adverse reactions than amphotericin B. A patient who was diagnosed as having agranulocytosis and thrombocytopenia after treatment with fluconazole was investigated and recovered after withdrawal of the antifungal therapy. This case suggests the need for careful haematological observation during the treatment with fluconazole. PMID- 1286743 TI - International symposium on the first steps towards an international harmonization of veterinary biologicals: 1993 and free circulation of vaccines within the E.E.C. Ploufragan, France, 14-16 January 1992. Proceedings. PMID- 1286745 TI - The procedure for marketing authorization for veterinary medicinal products derived from biotechnology in the European community. PMID- 1286744 TI - Development of a recombinant vaccinia-rabies vaccine for oral vaccination of foxes against rabies. AB - To improve both safety and stability of the vaccines used in the field to vaccinate foxes against rabies by the oral route, a recombinant vaccinia virus, expressing the immunizing G protein of rabies virus (VVTGg RAB-26D3 187 X P strain) has been developed. The c-DNA corresponding to the glycoprotein of the ERA strain of rabies virus has been inserted into the thymidine kinase (TK) gene of the vaccinia virus (Copenhagen strain). The efficacy of this recombinant strain was tested by the oral route, primarily in foxes. The duration of immunity conferred by the VVTGg RAB, a minimum of 12 months in cubs and 18 months in adult animals, corresponds to the length of protection required for fox vaccination in the field. VVTGg RAB innocuity was tested in foxes and in domestic animals as well as in numerous wild animal species that could compete with the red fox in consuming vaccine baits in Europe. During a minimum of 28 days post vaccination, neither clinical signs nor lesions were observed in any of the vaccinated animals. Moreover no transmission of immunizing amounts of the recombinant occurred in the red fox or the other species tested. To study the stability of the vaccine strain, baits containing the vaccine were placed in the field. Despite considerable variations of environmental temperatures, the VVTGg RAB titre remained stable after one month in the field. Since all the baits are taken within one month, it can be assumed that most of the animals taking the baits are effectively vaccinated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286746 TI - Rabies vaccines for veterinary use: difficulties in establishing potency acceptability thresholds. AB - The variability of a control test is sometimes difficult to assess. In fact this variability should be considered as a common basis of any biological test. The example of the NIH or PER test is given for veterinary rabies vaccines. The same acceptability threshold is accepted by everybody, both producers and control laboratory. But biological variability should induce the producers to determine a "working acceptability threshold" higher than the conventional one. This safety margin should be determined by the producer to counterbalance the variability of the test both in the producer and control laboratories so that most batches submitted to the official control are accepted. On the other hand, control laboratories should fulfil two "fair" requirements: reveal their flow charts and their margin of error to allow the producer to make the needed adjustments; reduce as far as possible the uncertainty of control tests by using the most accurate statistical interpretation to allow the producers to establish a "working acceptability threshold" not too much higher than the official one. PMID- 1286747 TI - Control methods and thresholds of acceptability for antibrucella vaccines. AB - Protection against brucellosis involves both cellular and humoral effectors not yet fully appreciated. Living or killed vaccines can protect against the infection itself or only against abortion. For official controls, vaccines (or new procedures of vaccination) must first be characterized pharmacologically and tested for innocuity. Protection must be tested on natural hosts with a reference vaccine (S19 or Rev. 1) by the agreed method which reproduces the natural infection and measures immunity in toto. Control and vaccinated females are challenged by the conjunctival route at mid-pregnancy under standard conditions (strain, dose) to measure the resulting infection by bacteriological analysis of excretion at parturition and of infection in target organs at slaughter. Results are principally expressed by the infection rate which should be +/- 95% in the control group. In the new vaccine group the rate should be equivalent to, or lower than, the reference vaccine group. To be statistically valid, at least 30 animals per group are required. For routine controls, laboratory models using guinea pigs, not well standardized, inaccurate and expensive, have long been proposed. The mouse model, extensively studied and standardized, should now be preferred to the guinea pig model. In the mouse model, residual virulence of a living vaccine is estimated by the time required by 50% of the mice to eradicate the strain from their spleen (Recovery Time 50%). Immunogenicity is measured by the ability of mice to restrict their splenic infection after a virulent i.p. challenge at a dose (B. abortus 544; 2 x 10(5) cfu) chosen in order that all mice were still infected 15 days post challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286748 TI - Establishing an acceptability threshold for equine influenza vaccines. AB - Shortcomings in the original methods (based on haemagglutination of erythrocytes) used to measure potency of equine influenza vaccines and antibody responses stimulated by vaccines, coupled with the lack of a reliable challenge system in the target species, has hindered progress in identifying the antigenic content required to provide protection. Reliable methods are now available for measuring the haemagglutinin (HA) content of vaccines and the antibody responses they elicit. The development of challenge systems in the target species has allowed antibody levels consistent with protection to be identified under experimental conditions. Comparison of vaccine performance under experimental conditions and in the field suggests that exposure to a nebulised virus aerosol provides a realistic challenge for the assessment of equine influenza vaccines. PMID- 1286749 TI - Control of manufacture--principles and purposes. AB - The control of manufacture is centred on the assessment of the operation based on information supplied by the manufacturer and on detailed physical inspection. The purpose of controlling manufacture is to ensure, as far as practicable, that products are manufactured within premises, and by processes and personnel, of such standard that the quality of the final product is assured. The required standards are written in the "Guide to Good Manufacturing Practice for Medicinal Products", and its several supplementary guidelines, so in practical terms the purpose of inspection is to assess compliance with these guidelines. It is usual, however, for manufacturers' premises and practices not to comply with the guidelines in all respects. There is therefore a need to make judgements on the significance of, and risks associated with, these discrepancies. It is necessary to consider potential problems in the context of the overall manufacturing process, bearing in mind the nature of the products involved. A decision as to what remedial actions are required, and over what time-scale, is then made. PMID- 1286750 TI - Control of manufacture--the EC point of view. PMID- 1286751 TI - Inspection of veterinary biologics in the United States. AB - Inspection of veterinary biologics in the United States (U.S.) has changed significantly over the years since the Virus-Serum-Toxin Act (V-S-T) was passed by the U.S. Congress in 1913. At first, government inspectors were appointed to every production location, observing the preparation, testing and initial shipment of veterinary biologics. In the 1950s, a new plan was developed to provide a more scientific basis of inspection. Over a 10-year period, a programme to test finished products at the National Veterinary Services Laboratories and a new procedure for inspecting facilities and products was implemented. Our current programme retains our extensive pre-licensing review of products, labeling, facilities and personnel and adds the new inspection system of random checking of finished batches, unannounced in-depth inspections, control of product batches and post-licensing monitoring. This combination of activities ensures that pure, safe, effective and economical veterinary biologics are available for use in the U.S. PMID- 1286752 TI - Licensing veterinary biologics in the United States. AB - The authority for the regulation of veterinary biologics in the United States is provided in the Virus-Serum-Toxin Act, enacted in 1913 and amended in 1985. The Act authorizes the Secretary of Agriculture to prescribe regulations governing the preparation and marketing of veterinary biologics shipped into, within, or from the United States. The veterinary biologics program carries out the mandate to ensure that all veterinary biological products under the U.S. jurisdiction are pure, safe, potent, and efficacious. The program is based on licensing, inspection, and testing. Establishment licensing defines the production facilities, manufacturing practices, and the responsible person. Product licensing defines the product, the method of production, and testing requirements; it also assures product purity, safety, potency, and efficacy. Biologics production is based on the Master Seed concept, in which a master parental stock is the source of all seed materials for production. The final product may not be more than five serial passages removed from the Master Seed. Host animal immunogenicity is demonstrated by statistically valid host animal vaccination and challenge studies using the minimum level of antigen at the highest level of passage. Potency tests are correlated to host animal immunogenicity and are conducted on each serial of product prior to release for marketing to assure efficacy. Conditional licensing procedures that assure purity, safety and a reasonable expectation of efficacy are used to provide products for emergency conditions, limited markets, local situations, or other special circumstances. Licensing for further manufacturing permits two or more licensees to work together in the production of a product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286753 TI - Control of product batches (before and after registration). The German approach. AB - At present, batch control is performed after a product is licensed. The range of batch control tests and the detailed description of these tests are fixed for every product during the respective authorization procedure. In an increasing number of cases it also seems necessary to test the prelicensing batches, which are used in the clinical trials for efficacy and safety. The batch control performed in the Paul-Ehrlich-Institute consists of the control of the batch protocols and the practical control of product samples. The practical testing includes purity, efficacy and safety of the batch. Considerable quality differences occur from one batch to another, even when the batch-to-batch consistency is documented during the authorization procedure. Moreover, without previous indication to the state authority, the authorized control tests are frequently modified by the producer or are not performed for each batch. Some examples of these occurrences are presented. In addition it is necessary to bear in mind that the production of vaccines and sera needs biological seed materials, the quality of which can never be so uniform in the way chemical substances normally are. Since most of the incidents which occur when using vaccines and sera are batch-related and not product-related, the continuous batch control by state authorities is considered to be necessary. PMID- 1286754 TI - Control of product batches (before and after registration). The British approach. AB - In the United Kingdom, some pre-registration testing of immunological products is carried out. However, this is normally not extensive. Usually the tests are laboratory tests undertaken to verify results obtained by the manufacturer or quality controller. For many years, routine post-registration testing of batches of immunological products has been carried out. However, this has ceased and had been replaced by a new system known as the Quality Assurance/Quality Control (QA/QC) scheme. The new scheme is designed to provide the Veterinary Medicines Directorate (VMD) with assurance of the continuing quality of batches of immunological products. The basis of the scheme is a system of inspection of companies' quality control facilities and procedures, every eight months, by staff with appropriate microbiological qualifications and experience. Before an inspection is carried out, the company must provide detailed documentation on the facilities and the quality control procedures used for each product. This provides the inspector with the background information for the inspection and discussions with the company. PMID- 1286755 TI - Control of product batches (before and after registration). The French approach. AB - The issue of investigation into vaccine files and control in general has always been a delicate one. There are considerable economic and medical interests. The supervisor should not then thwart a step towards progress and should not appear as an economic brake. Yet he should guarantee to the users a certain quality in the marketed biological products. According to these principles, recommendations have been formulated to indicate tests that should be realized by manufacturers and related in files of request for Marketing Authorization. Consequently the level of requirements may seem quite high in France. But partners involved in the investigation of files and in vaccine controls as well as those who are concerned with the marketing of new biological products should guarantee their quality. In addition to investigating the file, controls are undertaken in France by State laboratories which specialize in a particular species. They are also applied research laboratories. These controls aim at checking the manufacturers' results. In France no systematic control is undertaken on successive vaccine batches before marketing. Controls are undertaken at random if information coming from users gives rise to suspicion about a vaccine or batch of vaccines which are causing problems. However systematic controls should be undertaken by a private or State laboratory for imported batches. In future, only control results will probably be required. However batch-to-batch controls are undertaken by a state laboratory for rabies vaccines and tuberculin. In conclusion, in France we favour controls before Marketing Authorization together with high specifications for manufacturers. State batch-to-batch control is not undertaken since present means do not encourage such a procedure, the interest of which are not obvious; furthermore, this procedure remains very restricting for manufacturers. PMID- 1286756 TI - Control of product batches (before and after registration). The Belgian approach. AB - A review is given on the registration procedure and controls of veterinary vaccines in Belgium. An obligatory registration procedure was installed in 1969, and has since been modified several times. The Belgian approach for control of veterinary vaccines before and after registration is explained. Controls before registration are often carried out exclusively by the manufacturer and are described in the registration file. Controls may, however, also be carried out by an independent laboratory if the manufacturer so desires. In general, the procedures described in a national or European Pharmacopoeia must be applied if a monograph is available. Batch control after registration is carried out by the manufacturer. When manufactured in Belgium, controls on the finished product must also be carried out by the Institute of Hygiene for viral vaccines and some selected bacterial vaccines (e.g. anthrax). In addition, all batches of imported vaccines are subject to controls both by an officially accepted laboratory and by the Institute of Hygiene, the first to be paid by the importer, the second free of charge. Batch controls include homogeneity of the batch, labelling, storage conditions and also identity of active component(s), safety, sterility, absence of extraneous agents and potency. The potency test described in the original registration file must be used for batch control. PMID- 1286757 TI - Testing of veterinary biologics in the United States. AB - The National Veterinary Services Laboratories (NVSL) in Ames, Iowa, are responsible for the confirmatory testing of veterinary biologics produced in the United States and regulated by the United States Department of Agriculture. There were 22.101 serials of biological products produced and submitted to the NVSL during fiscal year (FY) 1991 (October 1, 1990, to September 30, 1991). All serials were tested by the manufacturer; and 2.086 (9.44 percent) were also tested by the NVSL for purity, safety, or potency of at least one component. Of the serials tested, 97.84 percent were found to be satisfactory. The total number of tests conducted during FY 1991 was 4.283. The criteria for establishing test rates and test methods are discussed. In addition to the testing of finished biological products, the NVSL tested 129 bacterial or viral master seeds and 31 master cell stocks during FY 1991 for identity and freedom from extraneous bacterial and viral agents. These master seeds and master cell stocks will be used to make future biological products. PMID- 1286758 TI - The cost of quality assurance/quality control. AB - Good Manufacturing Practice Guidelines have an inherent philosophy to maintain high standards and to promote uniformity within trading areas. Reaching these standards in some countries and maintaining them in others is costly. The Cost of Quality is regarded as a significant indicator of business performance. Quality costs are increasing as demands for improved accuracy and precision are made on the industry. The paper also details actual costs for validating a modern biological production facility and establishing biological quality control facilities. Bench mark quality control testing costs for a typical large and small animal vaccine are given. PMID- 1286759 TI - FEDESA's point of view: quality, application to IVMPs (immunological veterinary medicinal products). PMID- 1286760 TI - The FEDESA's point of view. PMID- 1286761 TI - The future European system for the free circulation of veterinary vaccines in Europe. AB - Although Community legislation has only recently been extended to cover veterinary biologicals, these products are fully covered by the recent Commission proposals for the free movement of medicinal products after 1992. The proposals are based on more than 25 years of harmonization of national regulations and more than 10 years' experience of coordinating national decisions on individual medicinal products. The proposals envisage the establishment of two new Community authorization procedures: a centralized procedure based on a single scientific evaluation of the highest possible quality to be undertaken within a new European Medicines Evaluation Agency, leading to a binding EEC-wide decision, with the possibility of limited exceptions to take account of differences in disease status in the Member States; a decentralized procedure based on the concept of mutual recognition of national decisions, with binding Community arbitration in the event of a dispute. To provide the Community institutions with the scientific and technical resources necessary to operate these new procedures, the proposals also provide for the establishment of a European Medicines Evaluation Agency. PMID- 1286762 TI - Veterinary vaccines in an economic and sociopolitical context. The viewpoint of the veterinary pharmaceutical industry. PMID- 1286763 TI - Presentation of the EEC directive (81/852)--quality. AB - The EC directive 81/852 has been revised to include a number of parts setting out the information to be included in applications for marketing authorizations for veterinary immunological products. Part 6 contains the details of the quality aspects which must be addressed by the applicant. It is divided into sections and provides the applicant with the structure and layout to be used for the presentation of the information in the dossier. The applicant must provide sufficient detail to allow the competent authority to assess the quality of the product, including aspects such as batch-to-batch consistency and the risk of contamination of batches with extraneous agents. Thus the dossier must contain details of the starting materials, the method of manufacture, and the controls and tests on the starting materials and intermediate and finished products. The details of the blending and composition must be included. Limits of acceptance should be provided. Procedures used such as inactivation and purification steps and quality control tests should have been shown to be appropriate and the results of the validation studies must be presented. The information supplied must be accompanied by results obtained from batches manufactured by the method described. A justification of the proposed shelf-life of the product must be made with supporting evidence from real-time stability studies. PMID- 1286764 TI - Some remarks on the efficacy of vaccines for veterinary use. PMID- 1286765 TI - Presentation of the directive 81/852/EEC (92/18) safety testing. AB - The aim of the directive is to define tests to be done by a manufacturer which are capable of providing as precise information as possible about the properties of the biological products concerning safety. These tests have to be done in the target species and the dose used should be that quantity of the product recommended for use and containing the maximum titre of potency. The samples for safety testing should be taken from a batch produced according to the manufacturing process. The vaccine is tested in normal conditions at the recommended dose and by each recommended route of administration to animals of each species and category it is intended to vaccinate. Objective criteria have to be recorded to measure possible adverse general and local effects. But tests in abnormal conditions of use may be necessary, such as administration of an overdose or repeated administration of one dose. Effects on reproductive function and progeny have to be studied as well as investigations which may be required in some cases to evaluate a possible adverse effect on the immunological function of the vaccinated animal. Special requirements seem to be appropriate for live vaccines: to evaluate the spread of the vaccinal strain from vaccinated to unvaccinated animals including, if necessary, wild species; to determine whether the vaccinal strain can disseminate in the vaccinated organism; to check for the absence of reversion to virulence of live stains especially for conventional vaccines. Field studies can therefore provide complementary information about safety. PMID- 1286766 TI - Technical requirements of veterinary vaccines for registration--FEDESA's point of view. PMID- 1286767 TI - Current USDA procedures for licensing biotechnology-derived veterinary biologicals. AB - The establishment of appropriate procedures for regulating the commercialization of biotechnology products is an international issue which has been debated extensively in many countries. This paper will discuss the current procedures that have been established for the regulation of biotechnology-derived veterinary biologicals within the United States Department of Agriculture (USDA) and more specifically within Biotechnology, Biologics, and Environmental Protection (BBEP) of the Animal and Plant Health Inspection Service (APHIS). These procedures implement recent BBEP regulatory policy that has been developed to ensure risk based regulation and avoid excessive restrictions that might curtail the development of biotechnology products. PMID- 1286768 TI - The American manufacturer's view on the EEC texts and harmonization. AB - In a world that has become increasingly smaller with the aid of modern air travel, computers and facsimile machines, the European Community's efforts toward harmonization are applauded by the Animal Health Institute, representing the major U.S. manufacturers of veterinary biological products. The new and proposed directives and guidelines are based on the latest technology and help ensure that only high-quality safe and effective veterinary biologicals are registered in the European Community. These new legislations are, however, significantly different from the current United States (USDA) licensing requirements. The USDA requirements are designed to ensure the safety and efficacy of veterinary biologicals licensed in the United States and have been effective in doing so. Among major differences between EEC and USDA requirements are the EEC requirements for GLP safety tests, GMP for manufacturing, with increased measures for the prevention of cross-contamination, duration of immunity data, and raw material specifications in excess of those required in the United States. Very tight deadlines for implementing these requirements have been established. In the spirit of international harmonization and with the goal of reducing or preventing potential trade barriers, the AHI would like to propose the formation of an international working group consisting of FEDESA, AHI, CVMP, USDA and other international industry and government officials. It is suggested that annual meetings be held in conjunction with either FEDESA or AHI meetings. Issues to be dealt with include standardization of test requirements, time lines for implementation and other issues that could reduce or prevent trade barriers without adversely affecting product quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1286769 TI - The role of the European Pharmacopoeia. PMID- 1286770 TI - The role of the Office International des Epizooties in the standardisation of biologicals. AB - The Office International des Epizooties (OIE) is the World Animal Health Organisation created in 1924 in Paris. The following activities have been started in order to promote standardisation of biologicals: a) preparation of the OIE Manual of Standards for Diagnostic Tests and Vaccines; b) organisation of Reference Laboratories for diseases of Lists A and B; c) establishment, in cooperation with WHO, FAO and IAEA, of international standards for diagnostic tests with particular reference to the ELISA. The Manual will be distributed worldwide in 1992 and 1993 and this will contribute to an internationally unified approach to diagnosis and immunoprophylaxis, in other words to international harmonisation of veterinary biologicals. It is planned that future OIE Reference Laboratories, now being organised, will supply the necessary standards. PMID- 1286771 TI - The issue of new generation vaccines. Hierarchy of the risk. PMID- 1286772 TI - Regulation of Drosophila neural development by a putative secreted protein. AB - The Drosophila strawberry (sty) locus was isolated by P-element insertion mutagenesis in a screen for mutations affecting eye development. Analysis of the mutant phenotype and the putative expression pattern of the sty gene suggested that it has multiple functions. Mutations in the sty gene lead to irregular spacing of ommatidia, an increase in the number of photoreceptor cells, as well as abnormal axonal projections to the lamina and disrupted structure of the optic lobes in the adult fly. The sty mutation also causes abnormal head involution, a change in a number of sensilla in the antennomaxillary complex in the embryonic stage and abnormal morphogenesis of the maxillary palp and wings in later stages. We examined the presumptive expression of the sty gene during development by histochemical staining for lacZ expression from enhancer trap elements inserted within the sty gene. During embryogenesis, expression of lacZ showed a segmental pattern in the ectoderm and in the nervous system. In the eye imaginal discs, lacZ was expressed in photoreceptor cells beginning a few rows posterior to the morphogenetic furrow. The lacZ was also expressed in the wing disc. In the adult, lacZ was expressed in the retina and lamina. We cloned the sty gene by P-element tagging and found that it encodes a putative secreted protein containing a cysteine-rich region similar to the epidermal growth factor (EGF) repeat. On the basis of the loss of functional phenotype, the expression pattern and the predicted structure of its product, we propose that sty encodes a diffusible protein acting as a signal involved in lateral inhibition within the developing nervous system and also as a factor involved either directly or indirectly in axonal guidance and optic lobe development. PMID- 1286773 TI - Modulation of the invasive phenotype of human colon carcinoma cells by organ specific fibroblasts of nude mice. AB - We examined whether fibroblasts from subcutaneous, colon or lung tissues of nude mice influence the invasive potential of highly metastatic human colon carcinoma KM12SM cells. Primary cultures of nude mouse fibroblasts from skin, lung and colon were established. Invasive and metastatic KM12SM cells were cultured alone or with fibroblasts. Growth and invasive properties of the KM12SM cells were evaluated as well as their production of gelatinase activity. KM12SM cells were able to grow on monolayers of all three fibroblast cultures but did not invade through skin fibroblasts. The conditioned media of KM12SM cells cocultured with skin, colon or lung fibroblasts were examined for the presence of type IV collagenase (gelatinase). KM12SM growing on plastic and on colon or lung fibroblasts produced significant levels of latent and active forms of 64 kDa type IV collagenase, whereas KM12SM cells cocultivated with nude mouse skin fibroblasts did not. In contrast, human squamous cell carcinoma A431 cells produced significant levels of collagenase type IV when cocultured with nude mouse skin fibroblasts, a tissue they invaded and completely penetrated. Incubation of KM12SM cells in serum-free medium containing recombinant human interferon-beta (fibroblast interferon) was associated with significant reduction in gelatinase activity. Since the production of type IV collagenase by human colon cancer cells is specifically inhibited by mouse skin fibroblasts but not by colon or lung fibroblasts the data suggest that organ-specific fibroblasts can influence the invasive and metastatic properties of KM12SM cells. PMID- 1286774 TI - Differential and stage dependent effects of retinoic acid on chondrogenesis and synthesis of extracellular matrix macromolecules in chick craniofacial mesenchyme in vitro. AB - Retinoic acid (RA) is well known to be a potent teratogen and induces a variety of facial defects in vivo, but at concentration levels lower than those that cause facial defects, RA seems to play an important role in normal facial development. In a previous study, we demonstrated the ability of RA to stimulate chondrogenesis in vitro in HH stage 23/24 chick mandibular (MND) but not frontonasal (FNP) mesenchyme cultured in a serum-free medium. The present study furthers these results by examining the effects of RA on chondrogenesis of chick facial mesenchyme at earlier embryonic stages and the effects on cell proliferation and synthesis of specific extracellular matrix macromolecules at stage 23/24. MND and FNP cells were cultured as micromasses for 4 days in defined media. As described previously, chondrogenesis in stage 23/24 MND cells was significantly enhanced by concentrations of RA of 0.1-1 ng/ml; however, at all earlier stages examined (18 to 22) RA at these concentrations had no significant effect. Higher concentrations of the retinoid inhibited chondrogenesis in MND cultures from all stages tested. Cells of the FNP from all stages displayed no significant change in chondrogenesis below 1 ng/ml RA and a dose dependent inhibition at higher concentrations. Thus RA's promotional effects in the face are not only tissue specific (MND), but also stage-dependent (HH 23/24). The specific effects of RA on matrix production and cell proliferation of stage 23/24 MND and FNP cells was examined by analysis of 35S sulfate, 3H thymidine and 3H proline incorporation. Analysis of 35S sulfate incorporation into sulfated proteoglycans confirmed that concentrations of RA of 0.1-1 ng/ml stimulated cartilage matrix production in MND but not FNP cultures. Above this level of RA, 35S sulfate incorporation was reduced in both. Likewise, 3H proline incorporation into collagenous protein, and to a lesser extent non-collagenous proteins, was stimulated by low levels of RA in MND, but not FNP cultures. Higher concentrations of the retinoid in either MND or FNP cultures did not lower collagen production, undoubtedly due to stimulation of non-chondrogenic cells within the population. This indicates that levels of RA as high as 100 ng/ml cause phenotypic change rather than cell death. This last point is corroborated by the analysis of 3H thymidine uptake in the cultures which was only transiently modified in most. The data indicate that cell proliferation occurred even in the presence of high RA levels. PMID- 1286775 TI - Identification of a short nuclear lamin protein selectively expressed during meiotic stages of rat spermatogenesis. AB - The nuclear lamina is a karyoskeletal structure located at the nuclear periphery and intimately associated with the inner nuclear membrane. It is composed of a multigene family of proteins, the lamins, which show a conspicuous cell type specific expression pattern. The functional role of lamins has not been definitively established but available information indicates that they are involved in the organization of nuclear envelope and interphase chromatin. Spermatogenesis is characterized, among other features, by stage-specific changes in chromatin organization and function. These changes are accompanied by modifications in the organization and composition of the nuclear lamina. In previous experiments we have determined that rat spermatogenic cells express a lamin closely related, if not identical, to lamin B1 of somatic cells; whereas rat somatic lamins A, C, D and E were not detected. Considering that chromatin reorganizations during spermatogenesis may be directly or indirectly related to changes of the nuclear lamina we have decided to further investigate lamin expression during this process. Here we report on the identification of a 52 kDa protein of the rat which, according to immunocytochemical and biochemical data, appears to be a novel nuclear lamin. Using meiotic stage-specific markers, we have also demonstrated that this short lamin is selectively expressed during meiotic stages of spermatogenesis. PMID- 1286776 TI - Distribution of hyaluronan in the mouse endometrium during the periimplantation period of pregnancy. AB - The tissue distribution of stromal hyaluronan (HA) in the periimplantation mouse uterus was studied histochemically using a biotin-labelled HA-binding complex from cartilage proteoglycan. HA is present around proliferating stromal cells in both the pregnant and pseudopregnant mouse uterus prior to their differentiation into the decidualized phenotype. Decidualization is accompanied by clearance of HA from the extracellular matrix (ECM). This clearing is part of an intrinsic developmental program of the differentiating deciduum. A specific embryonic signal from the implanting conceptus is not required for this phenomenon to occur, since a similar response could be induced in deciduoma produced by artificial stimulation of a receptive uterus. Clearing of HA from the antimesometrial stroma is consistent with the hypothesis that the HA-negative decidual cell may be involved in restricting the invasion of trophoblast cells during embryo implantation. Retention of HA within angiogenic regions of the decidua basalis implies a functional role for this molecule in placental vascularization. PMID- 1286777 TI - Developmental regulation of class I major histocompatibility complex antigen expression by equine trophoblastic cells. AB - Between days 36-38 of pregnancy equine trophoblastic cells of the chorionic girdle migrate and form endometrial cups. Just prior to invasion, the chorionic girdle cells express high levels of polymorphic, paternally inherited, major histocompatibility complex (MHC) class I antigens. Their descendents, the mature, invasive trophoblast cells of the endometrial cups, however, express low or undetectable levels of MHC class I antigens by day 44 of pregnancy. Experiments with MHC compatible pregnancies, the study of residual chorionic girdle cells that had failed to invade the endometrium and remained on the surface of a conceptus, and the study of chorionic girdle cells recovered on days 34-36 of pregnancy and then maintained in vitro for up to 24 days strongly suggest that the reduction of MHC class I antigen expression by mature invasive trophoblast cells of the endometrial cups is developmentally regulated. This phenomenon does not appear to be induced by a maternal antibody response or by other uterine factors acting after the chorionic girdle trophoblast cells invade the endometrium. PMID- 1286778 TI - Ascorbate independent differentiation of human chondrocytes in vitro: simultaneous expression of types I and X collagen and matrix mineralization. AB - In this study we describe the collagen pattern synthesized by differentiating fetal human chondrocytes in vitro and correlate type X collagen synthesis with an intracellular increase of calcium and with matrix calcification. We show that type II collagen producing fetal human epiphyseal chondrocytes differentiate in suspension culture over agarose into hypertrophic cells in the absence of ascorbate, in contrast to chicken chondrocytes which have been shown to require ascorbate for hypertrophic differentiation. Analysis of the collagen synthesis by metabolic labeling and immunoprecipitation as well as by immunofluorescence double staining with anti type I, II or X collagen antibodies revealed that type X collagen synthesis was initiated during the third week. After 4 weeks culture over agarose we identified cells staining for both type I and X collagen, indicating further differentiation of chondrocytes to a new type of 'post hypertrophic' cell. This cell type, descending from a type X collagen producing chondrocyte, is different from the previously described 'dedifferentiated' or 'modulated' types I and III collagen producing cell derived from a type II collagen producing chondrocyte. The appearance of type I collagen synthesis in agarose cultures was confirmed by metabolic labeling and immunoprecipitation and challenges the current view that the chondrocyte phenotype is stable in suspension cultures. An increase in the intracellular calcium concentration from 100 to 250 nM was measured about one week after onset of type X collagen synthesis. First calcium deposits were detected by alizarine red S staining in type X collagen positive cell nodules after 4 weeks, again in the absence of ascorbate. From these observations we conclude a sequence of events ultimately leading to matrix calcification in chondrocyte nodules in vitro that begins with chondrocyte hypertrophy and the initiation of type X collagen synthesis, followed by the increase of intracellular calcium, the deposition of calcium mineral, and finally by the onset of type I collagen synthesis. PMID- 1286779 TI - [Cardiac rhythm and arrhythmia in prolonged space flights]. PMID- 1286780 TI - [Individual features of psychophysiologic functions of first-year schoolchildren during adaptation to school]. PMID- 1286781 TI - [Brain mapping using point distribution of EEG-rhythms]. PMID- 1286782 TI - [Early components of subcortical visual evoked potentials in tests with omission of the expected stimulus]. PMID- 1286783 TI - [Illusion of visual target movement as affected by electric vestibular stimulation]. PMID- 1286784 TI - [Parameters of the functional state of athletes' cardiovascular system in distance diving]. PMID- 1286785 TI - [Topographic mapping of cerebral electric activity. Methodologic aspects]. PMID- 1286786 TI - [Variants of reactions of the blood coagulation system to graduated physical exercise]. PMID- 1286787 TI - [Functional significance of parameters of EEG spatial-temporal organization in patients with cranial-cerebral trauma]. PMID- 1286788 TI - [Frequency-spectral analysis and topographic mapping of brain electric activity in acute disorders of cerebral circulation]. PMID- 1286790 TI - [Informative value of various approaches to EEG mapping in the investigation of human psychic activity]. PMID- 1286789 TI - [Topographic EEG-mapping in child psychiatry]. PMID- 1286791 TI - [Spatial organization of EEG in right-handed and left-handed subjects during voluntary movements]. PMID- 1286792 TI - [Diagnostic significance of individual quantitative EEG changes during mental strain]. PMID- 1286793 TI - [Perception of music by healthy and depressed people]. PMID- 1286794 TI - [Functional organization of the human and left hemispheres in man during directed attention]. PMID- 1286795 TI - [Genetic relationships between European and Transcaucasian mice of the genus Apodemus Kaup]. AB - Genetic relations between four European mice species of the genus Apodemus (Apodemus sylvaticus, A. flavicollis, A. microps and A. falzfeini) and five Transcaucasian ones (A. mystacinus, A. microps, and the forms No 2, 3p, 3f) were studied for 37 biochemical loci. Close genetic relations were demonstrated between the mice of subgenus Sylvaemus and A. mystacinus. A. microps and A. falzfeini from the Caucasus were shown conspecific to these species from the Ukraine and the presence of the two new different species--the form No 2 and 3p in the Caucasus was established. PMID- 1286796 TI - [Molecular-genetic analysis of tandem repeats in intron 6B of the CFTR gene in various populations and in cystic fibrosis patients]. AB - Frequencies of hexa- and heptatandem tetrameric repeats in Russian slavonians from the North-Western part of the country were found to be 0.19 and 0.81, respectively, with the frequency of heterozygotes estimated as 0.31. Similar values of allelic frequencies were found for uzbek and azerbaijan populations (0.24 and 0.76; 0.22 and 0.78, respectively). These data assess the existence of genetic equilibrium of both alleles in the populations studied. Hexa TTR is present twice more often in the CF chromosomes than hepta TTR common for normal chromosomes. Absolute genetic disequilibrium of both TTR alleles was observed for CF chromosomes bearing the F508 mutation. The latter was exclusively detected in a conjunction with hexa TTR allele. Combined application of the F508 test and TTR alleles assay significantly increased the number of totally informative CF-high risk families, and thus might be highly beneficial for a subsequent prenatal diagnosis of CF. PMID- 1286797 TI - [Structure of phenotypic variability in readiness potential in 6-7 year-old children]. AB - This report is a part of a larger project, the major purpose of which is a longitudinal study of developmental changes in genetic control of variation in Bereitshaft potentials (BP). 15 pairs of MZ and 15 pairs of DZ twins aged 6-7 years participated in the BP study. 2 second epochs of EEC time-locked to the movement were digitized off-line at 500 Hz (DAS-16G "Metrabyte"), for 1500 msec, prior to and 5000 msec after movement. A complex BP waveform with the positive components was discovered in young children. We fitted four basic models to the twin data for each of the BP in F3, F4, C3, C4. Since the models (VA, EW) in F3, F4, C3 and (EB, EW) in C4 fit very well and cannot be improved markedly by adding the most important alternative parameters, we conclude that variation of BP of F3, F4, C3 is best explained by a very simple genetic model, and variation of BP of C4 is best explained by a simple environmental model. PMID- 1286798 TI - [Molecular nature of beta-thalassemia in Tajikistan: a four base pair deletion in codons 41-42 of the beta-globin gene]. AB - Thirty tajiks, whose relatives had beta-thalassemia traits (revealed in previous investigations by determination of the HbA-2 and HbF levels) were selected to screen beta-thalassemia mutations. DNA samples from each individual were subjected to the PCR (polymerase chain reaction) to amplify the 635 bp beta globin gene fragment. One additional band was detected in three samples after the amplified fragment underwent electrophoresis in 2% agarose gel and the EtBr was stained, and two additional ones were revealed by 6% PAAGE and staining of the EtBr. All additional bands migrated more slowly than appropriate 635 bp fragment. It is supposed that additional bands are heteroduplexes formed from the wild type chains and mutated chains carrying a deletion or insertion. The 4 bp deletion of the 41-42 (-tctt) was detected after the direct sequencing of the amplified fragments. This mutation is common among Chinese but it was not revealed in the Middle Asia populations. The mutation can be easily screened using the PCR and electrophoresis in 2% agarose gel or PAAG of the amplified beta-globin gene fragments. PMID- 1286799 TI - [Mapping of the focus of action of the lethal allele of the ecslt76 gene using genetic mosaics]. AB - Using gynandromorph the fate map of Drosophila melanogaster blastoderm was constructed. The focus of the lethal allele lt76 of the ecs gene was localised in two map sites. The site localized in the anterior part gives rise to the anterior region of the nervous system, and head. The latter covers the blastoderm anlages which are involved in the development of abdomen, and the genital imaginal disc. Interaction between two systems controlling morphogenesis is under debate. PMID- 1286800 TI - [Effect of mei mutations on the processes occurring in the double super-unstable system at the yellow and scute loci in Drosophila melanogaster]. AB - The influence of meiotic mutations on the mutation changes in the double super unstable system in the yellow and scute loci of Drosophila melanogaster was studied. The mei-41D5 and mei-218 mutations changed the spectrum and frequency of mutagenesis in males of the y2nsscme strain, in contrast to the postulate that meiotic mutations do not interfere with male recombination in D. melanogaster. These mutations also changed the frequency and spectrum of mutagenesis in females. In particular, they inhibited mutagenesis at early stages of ovogenesis. Meiotic conversion did not change specifically by mei mutations. At the same time, the mei-41D5 mutation increased all recombination processes in meiosis. The results obtained indicated the involvement of genetic recombination in mutation changes occurring in the double super-unstable system. Therefore, the latter may be successfully used in studies of the role of different genes and their products in recombination. PMID- 1286801 TI - [Genetic control of meiotic recombination in yeast]. AB - A review of research on genetic control of meiotic recombination is presented. The genes controlling different stages of meiotic recombination were revealed. Possible relationship of the gene products with the process of genetic recombination is under discussion. PMID- 1286802 TI - Recombination between the X and Y chromosomes and the Sxr region of the mouse. AB - The Sxr (sex-reversed) region that carries a copy of the mouse Y chromosomal testis-determining gene can be attached to the distal end of either the Y or the X chromosome. During male meiosis, Sxr recombined freely between the X and Y chromosomes, with an estimated recombination frequency not significantly different from 50% in either direction. During female meiosis, Sxr recombined freely between the X chromosome to which it was attached and an X-autosome translocation. A male mouse carrying the original Sxra region on its Y chromosome, and the shorter Sxrb variant on the X, also showed 50% recombination between the sex chromosomes. Evidence of unequal crossing-over between the two Sxr regions was obtained: using five markers deleted from Sxrb, 3 variant Sxr regions were detected in 159 progeny (1.9%). Four other variants (one from the original cross and three from later generations) were presumed to have been derived from illegitimate pairing and crossing-over between Sxrb and the homologous region on the short arm of the Y chromosome. The generation of new variants throws light on the arrangement of gene loci and other markers within the short arm of the mouse Y chromosome. PMID- 1286803 TI - Electrofusion of mouse embryos results in uniform tetraploidy and not tetraploid/diploid mosaicism. AB - Some previous attempts to produce tetraploids experimentally have resulted in a proportion of treated embryos becoming 2n/4n mosaics at a frequency which may be as high as 20%, when using cytochalasin B as a fusigenic stimulus and cytogenetic techniques to identify putative tetraploid embryos. To investigate the possible occurrence of 4n/2n mosaicism, tetraploid embryos were produced by electrofusion, a process which allows adjacent blastomeres at the 2-cell stage to fuse following exposure to electric field pulses. Embryos used for electrofusion were hemizygous for a transgene consisting of approximately 1000 copies of the mouse beta-globin gene. After in situ hybridization, one hybridization signal is expected per diploid genome. Tetraploid cells in 7.5-, 8.5-, 9.5- and 10.5-day-old conceptuses were distinguished from diploid cells by performing in situ hybridization on histological sections. The frequency of nuclei with two hybridization signals in the 'hemizygous' tetraploid embryos was compared to diploid embryos which were either hemizygous or homozygous for the beta-globin transgene. Comparison of the frequency of nuclei with two hybridization signals between tissues of 'hemizygous' tetraploid conceptuses and homozygous diploid conceptuses showed no significant difference, which implies that the tissues in the tetraploid conceptuses were uniformly tetraploid. No evidence was found to suggest that electrofusion results in 2n/4n mosaicism. PMID- 1286804 TI - The time of detection of recessive visible genes with non-random mating. AB - Expressions for the probability and average time of detection of a recessive visible gene in populations where there is partial selfing or partial full-sib mating are presented. A small increase in the proportion of inbred matings greatly reduces the average time until detection and increases the proportion detected. Unless the proportion of inbred matings or the population size is very small, the time and proportion detected are approximately independent of the population size. PMID- 1286805 TI - Estimating effective population size from samples of sequences: a bootstrap Monte Carlo integration method. AB - We would like to use maximum likelihood to estimate parameters such as the effective population size N(e) or, if we do not know mutation rates, the product 4N(e) mu of mutation rate per site and effective population size. To compute the likelihood for a sample of unrecombined nucleotide sequences taken from a random mating population it is necessary to sum over all genealogies that could have led to the sequences, computing for each one the probability that it would have yielded the sequences, and weighting each one by its prior probability. The genealogies vary in tree topology and in branch lengths. Although the likelihood and the prior are straightforward to compute, the summation over all genealogies seems at first sight hopelessly difficult. This paper reports that it is possible to carry out a Monte Carlo integration to evaluate the likelihoods approximately. The method uses bootstrap sampling of sites to create data sets for each of which a maximum likelihood tree is estimated. The resulting trees are assumed to be sampled from a distribution whose height is proportional to the likelihood surface for the full data. That it will be so is dependent on a theorem which is not proven, but seems likely to be true if the sequences are not short. One can use the resulting estimated likelihood curve to make a maximum likelihood estimate of the parameter of interest, N(e) or of 4N(e) mu. The method requires at least 100 times the computational effort required for estimation of a phylogeny by maximum likelihood, but is practical on today's work stations. The method does not at present have any way of dealing with recombination. PMID- 1286806 TI - Do Eve's alleles live on? AB - Consider a random sample of genes at a locus, drawn from a population evolving according to the infinitely many, neutral, alleles model. The sample will have a most recent common ancestor gene, which we shall call 'Eve'. The probability distribution, for the number of genes of oldest allelic type in a sample, is known and has a neat form. Rather less is known about the distribution for the number of genes in the sample which are of the same allelic type as Eve possessed. If the latter number is positive, then these genes are automatically of the oldest type in the sample. But Eve may have no non-mutant descendants in the sample; then, the oldest allele will be a mutant arising in a line of descent after Eve. The paper studies the number of non-mutant descendants from Eve, its distribution and moments. It seems that there may be few neat results. In large samples, the proportion of genes of Eve's type has an approximate beta-like density, together with a discrete probability atom at zero, if the mutation rate parameter is low. Extinction of the allele of even the population's common ancestor is possible, but not certain, and bounds are obtained for its probability. Some comments are made about the applications and implications of the results for human mitochondrial DNA. PMID- 1286807 TI - Surgical anatomy and dynamics in face lifts. PMID- 1286808 TI - The superficial musculoaponeurotic system: a clinical evaluation after 15 years of experience. PMID- 1286811 TI - Stretching and tissue expansion for face lift. PMID- 1286809 TI - The sub-SMAS and subperiosteal rhytidectomy of the forehead and middle third of the face: a new approach to the aging face. PMID- 1286812 TI - Adipoaspiration and "filling" in the face. PMID- 1286810 TI - Problems and variations in cervicofacial rhytidectomy. PMID- 1286813 TI - Face lifts in male patients. PMID- 1286814 TI - Fibrin glue in face lifts. PMID- 1286815 TI - Injectable collagen, chemical peeling and dermabrasion as an adjunct to rhytidectomy. PMID- 1286816 TI - New possibilities for facial nerve repair. PMID- 1286817 TI - Hypoglossal-facial nerve anastomosis. PMID- 1286818 TI - Muscle transposition for facial reanimation. PMID- 1286819 TI - Reanimation of paralyzed eyelids. PMID- 1286821 TI - Management of established facial palsy. PMID- 1286820 TI - Ancillary aids in the treatment of facial paralysis. PMID- 1286822 TI - Pathophysiology and assessment of the chronically paralyzed face. PMID- 1286823 TI - Facial lipotransplant surgery. PMID- 1286824 TI - Use of Mersilene mesh in nasal augmentation. PMID- 1286825 TI - Homographic cartilage in facial implantation. PMID- 1286826 TI - Injectable collagen. PMID- 1286827 TI - Facial augmentation with rolled mesh material. PMID- 1286828 TI - Injectable silicone: previous use and current status. PMID- 1286829 TI - The etiology of neonatal septal deviations. PMID- 1286830 TI - Primary and secondary nasal bone grafting after major facial trauma. PMID- 1286831 TI - Comparison of osteotomy techniques in the treatment of nasal fractures. PMID- 1286832 TI - Present day treatment of nasal fractures: closed versus open reduction. PMID- 1286833 TI - Growth of the deviated septum and its influence on midfacial development. PMID- 1286834 TI - Soft tissue trauma over the nose. PMID- 1286835 TI - Preface. Fracture of the nasal bones. PMID- 1286836 TI - Changes in superoxide dismutase and catalase in aging heat-shocked Drosophila. AB - We have examined the age-dependent expression of CuZn superoxide dismutase (SOD) and catalase (CAT) in Drosophila melanogaster following heat shock. Quantitative northern blot analysis was performed after heat shock on 2-, 23- and 49-day-old flies, using a 0.48 kb Sal1 EcoR1 fragment of the Drosophila SOD cDNA and a 1.4 kb fragment of the human catalase cDNA. Heat shock induction was monitored with a 5.4 kb DNA fragment of the Drosophila hsp70 gene. After exposure to 37 degrees C for 30 min and 60 min, the level of SOD RNA in young flies was elevated above that of nonstressed conditions. Changes in the transcription of SOD gene with age paralleled the expression of hsp70 RNA. The SOD RNA was elevated in heat-shocked middle aged (23-25 days old) flies compared to young Drosophila (2 days old), then it decreased in 49-50-day-old flies. The relative expression of CAT RNA did not change with age or after heat shock. Enzymatic activities of these two antioxidant enzymes were evaluated in nondenaturing polyacrylamide electrophoresis gels. SOD migrates on this gel as three different electromorphs. These were designated as fast, intermediate and slow migrating bands. The most intense activity was associated with the fast band in these flies. In the absence of heat shock, there was an age-dependent decrease in the intermediate, but not in the slow or fast bands. Heat shock does not affect the intensity of the fast band in young or old flies, however; in middle aged flies, there is a shift in this band toward the slow position. No change was detected in the activity of catalase with age or heat shock, although flies of all ages exhibited a shift toward a faster-migrating electromorph with increasing time of heat shock. This effect was also observed in flies fed H2O2 and is more pronounced in insects fed higher concentrations. These results are discussed in relation to the role of these antioxidant enzymes in protecting against age-induced oxidative stresses. PMID- 1286837 TI - [Evaluation of central speech disorders using objective criteria: a psychophysiologic contribution to the discussion of the neural plasticity hypothesis]. AB - Examinations of aphasic patients by using cognitive tasks were based on the hypothesis that semantically evoked potentials correlate to the processing of information in the different speech processing of information in the different speech processing areas. It was found that patients with Broca aphasia generated synchronization potentials in the Wernicke area in contrast to Wernicke patients. We suppose a correlation between the timing in sensorial speech processing areas and the generation of synchronization potentials. PMID- 1286838 TI - [Dysphonia following strumectomy with normal respiratory movement of the vocal cords]. AB - Voice function was phoniatrically investigated pre- and postoperatively in 66 patients undergoing thyroidectomy. Postoperatively we found a disturbance of the voice in 25 patients (43%), though there was a normal function of the recurrent laryngeal nerve. Typical symptoms were a reduced average pitch of the speaking voice, a lowering of the upper and the lower limit of the range of pitch, a lower volume and a fast fatigue of the voice. Eight times the voice remained reduced, even 6 months postoperatively. The cause is not seen in a neural lesion but in a disturbance of the prelaryngeal musculature. The frequency of the voice changes emphasizes the importance of the phoniatric examination, especially in patients who need their voice professionally. PMID- 1286839 TI - Characterization of the electroglottographic waveform: a primary study to investigate vocal fold functioning. AB - To objectify the vocal fold functioning we opted for a method of processing the electroglottographic (EGG) signal. This study with 7 normal and 12 pathological voices presents the results of measurements over the chest register as a function of voice intensity and frequency. Reproduction measurements show that at least 5 measurements per intensity/frequency pair are needed to get a reasonable estimation of the EGG parameters. The averaged results over about 20 measurements in the chest register showed differences for some parameters for subjects in the most different categories. To get more consistent results we recommend to improve the measurement protocol and adjust the parameters. PMID- 1286840 TI - Transitional determinacies. AB - In classic generative grammar a distinction is drawn between linguistic 'competence' and linguistic 'performance', the former referring to linguistic knowledge, the latter to how linguistic knowledge is used. However, this controversial differentiation obscures the additional dichotomy between linguistic knowledge for production and linguistic knowledge for recognition. In this article it is shown that production and recognition differ, that recognition is not simply the inverse of production, and that the derivation of production from recognition and recognition from production require a small set of generalizable 'transitional determinacies'. Secondly, it is shown that transitional determinacies explain the difference between 'overt' and 'covert' recognition recently observed in prosopagnosics, patients unable to recognize familiar faces. Prosopagnosics and normals are found to differ in their transitional determinacies, such that prosopagnosics require more binders (precisors) for covert recognition than normals. In general, it is concluded that transitional determinacies are as necessary to the theory of grammar as determinacies themselves. PMID- 1286841 TI - Sound spectra in cleft palate patients with a Sanvenero-Rosselli and modified Honig secondary velopharyngeal flap. AB - The averaged sound spectra produced by cleft patients with a Sanvenero-Rosselli (SR, n = 4) and modified Honig (MH, n = 4) velopharyngeal flap were compared with each other and with the spectra produced by 4 healthy controls. Each subject produced 16 sound spectra; the total number of spectra was 432. The results indicated that the averaged sound spectra produced by MH patients resembled more closely the spectra produced by healthy controls, while the spectra by SR patients differed from those of MH patients and controls. It was concluded that the differences in the averaged spectra of SR and MH patients reflected differences in the region of the oral cavity, particularly the oropharynx rather than the region of the nasopharynx. The results of this preliminary study indicate that this topic is worth further studies. PMID- 1286842 TI - Perceptual comparison of neoglottal, oesophageal and normal speech. AB - The sex, normality, intelligibility, rate, rhythm and intonation of 44 neoglottal, oesophageal and normal speakers have been judged by a panel of 10 trained listeners. It was found that the sex of the alaryngeal speakers was perceived correctly much less reliably than that of the normal speakers. Neoglottal speakers were rated more normal and intelligible than oesophageal speakers. The speaking rate of neoglottal speakers was judged not to be significantly different from that of normal speakers. Neoglottal speakers were considered more fluent and to have better intonation than the other alaryngeal speakers. Thus neoglottal speakers were found, on average, to be as good as or better than good oesophageal speakers in each of the respects of which judgements were made. PMID- 1286843 TI - [Importance of the EEG in early and differential diagnosis of dementia of the Alzheimer type]. AB - The development of new parameters in the quantitative evaluation of EEG provides new diagnostic opportunities for the clinician. Reviewing all published papers on EEG and dementia over the last 10 years revealed 30 out of 428 studies discussing EEG alterations in relation to the severity of the disease. This approach provides useful information for early and differential diagnosis of dementia. Besides a generalised slowing-down represented by an increase of delta and theta and a decrease of alpha and beta in the frequency spectrum (also characterised by a reduction of the peak frequency), the topography of the alterations changes depending on the severity of the disease. For instance, the alpha activity loses its normally occipital orientation. In early stages of the disease, it is measured parietally ("anteriorized"). In advanced stages, the activity is equally distributed over the scalp. Some studies found significant alterations even in early stages of the disease, most pronounced in theta and beta activity, making the EEG a useful tool for the early diagnosis of dementia. But studies on the differential diagnostic value are lacking. The value of EEG could be improved after parameters like the EEG segmentation or the traditional parameters combined with cognitive stimulation have been sufficiently evaluated. PMID- 1286844 TI - [Electroencephalographic findings in dementia diseases]. AB - Even if generally the EEG cannot yield specific pointers that are typical for a special pattern of dementia, it is nevertheless meaningful and helpful to perform routine EEG in demented patients. EEG is the functional additional examination that does not place any stress on the patient and is easy to perform at a low cost (1). As a functional diagram the EEG reflects the electrical processes taking place in the cerebral cortex, yielding an excellent image of the cerebral functional state. Assessment of the EEG is done in accordance with internationally standardised criteria. Particular attention is directed at a slowing-down of the background activity, the occurrence and extent of scattered theta and delta waves, their topographical distribution and the development of pathological EEG characteristics during recording (44). Update spectral analysis EEG procedures, i.g. the possibility to calculate power spectra for the individual EEG frequency bands and their topographic distribution, it may be possible in the near future to further improve differentiation between normal and pathological EEG findings. The functional dynamic aspect of the EEG is its particularly strong point in the differential diagnostic clarification of dementia patterns. By repeated EEG recordings, i.e. by close follow-up, and by relating the electrophysiological findings to the clinical pattern, reliable pointers are obtained for the extent of the activity of the process underlying the dementia pattern. EEG is predestined like no other method to enable early detection of rapid changes in cerebral function thanks to its easy operation and unlimited repeatability. The occurrence of parenrhythmic theta and delta waves in the EEG reflects in a special manner the acuity of an organic basic process. In this way EEG enables differentiation between acute and chronic processes of cerebral damage. Over and above this, correlation with the relevant clinical findings makes it possible to differentiate between reversible states of dementia and irreversible defect syndromes and hence also to point to the long-term outcome. Finally, the occurrence of certain patterns of findings or the identification of characteristic wave forms allows essential differential diagnostic pointers and definitions. PMID- 1286845 TI - [Neurologic concomitant diseases in Crohn disease]. AB - Disturbances of the central and peripheral nervous system in Crohn's disease can be directly or indirectly caused by the disease itself or by the treatment. The first mentioned disturbances are very seldom. Cerebral arterial and venous thromboses can be attributed to hypercoagulation. Malabsorption of vitamin B 12 or folic acid can lead to a subacute combined degeneration of the spinal cord, sometimes in combination with a polyneuropathy and an encephalopathy. Spinal abscesses very seldom occur. An opticusneuropathy can be caused either by vasculitis or by a lack of vitamin A and/or vitamin B. Polyneuropathies in Crohn's disease which are not induced by drugs are manifested as mononeuritis multiplex or as symmetrical sensory neuropathy. An autoimmune process is being discussed as the probable cause of there diseases. In some cases large doses and prolonged administration of metronidazole can lead to cerebral dysfunctions with state of confusion, alterations of consciousness, cerebral convulsions and cerebellar syndrome. Most of these symptoms disappear rapidly after this drug is not longer administered. In long-term administration of metronidazole 10-50% of the patients develop a sensory polyneuropathy with a total dosis of at least 22.5 g, but mostly above 60 g. After the use of metronidazole is stopped, it takes a substantial period of time until there is a full recovery from the symptoms. PMID- 1286846 TI - Noninvasive approaches to pain control in terminal illness: the contribution of psychological variables. AB - Pain is a common problem for patients with terminal illnesses. The major efforts to control pain for these patients have focused on the appropriate uses of analgesic medication to reduce the sensory aspect of the pain experienced. There are a number of studies in the chronic pain literature, however, that have implicated the important role of a number of psychological factors in the maintenance and exacerbation of pain. Among the most important variables identified are expectancy, anxiety, perceived controllability, self-efficacy, symptom preoccupation, operant conditioning, classical conditioning, and observational learning. In this paper, these psychological variables are examined and their applicability to patients who have pain associated with terminal illnesses is discussed as well as the implications of these variables for complementary treatment with analgesic medications are described. PMID- 1286847 TI - Pain relief using cutaneous modalities, positioning, and movement. AB - Positioning, movement, and certain cutaneous modalities may be easily used by all caregivers, including the family, to bring comfort and pain relief to terminally ill patients with pain. For such patients, these techniques are most appropriately used in addition to pharmacologic control of pain. Patients themselves may use some of the cutaneous modalities with minimal assistance from others, thereby promoting a sense of independence. Other techniques may be performed by family and friends, providing them with the assurance that they are assisting a loved one. The techniques presented here can be readily used in the home or hospital setting and are relatively low risk, simple, and inexpensive. This paper presents specific guidelines for patients and caregivers in relation to the use of superficial massage, superficial heat and cold, menthol application to skin, transcutaneous electrical nerve stimulation (TENS), positioning, and movement. Because of their simplicity and ease of use, these techniques tend to be overlooked. However, taking the time to introduce these techniques to patients and families often results in a significant contribution to the comfort of the dying patient. PMID- 1286848 TI - Involvement of families in pain control of terminally ill patients. AB - Pain associated with terminal illness is an extremely stressful problem for the patient as well as family members. Helping family members cope increases their effectiveness as caregivers and improves their own quality of life. Conversely, improving the patient's ability to cope decreases stress on other family members. Optimal treatment of pain in the terminally ill may be conceptualized and administered from a family perspective. Methods for helping families of terminal pain patients cope are organized around a theme of enhancing feelings of control and self-efficacy. Control over pain and related problems may be maximized by providing education, improving decision making and assertiveness skills, and by teaching specific techniques for pain and stress management, including proper analgesic use, progressive relaxation, imagery, distraction techniques, and time management. These techniques are described from a family perspective in this paper. PMID- 1286849 TI - The role of patient education in cancer pain control. AB - Patient education should be a central component of pain control regimens for cancer patients. Few systematically developed and carefully evaluated pain control patient education programs have been reported. Patient education for cancer pain control should include five phases: assessment, goal setting, selection of educational strategies, implementation and reassessment. Each of these phases should be included to maximize the goals of pain prevention and pain relief. PMID- 1286850 TI - Facilitating the use of noninvasive pain management strategies with the terminally ill. AB - In this paper a number of issues that appear to transcend the range of noninvasive interventions described in this volume are examined. Specifically, we raise the important issue of barriers to treatment. Among those discussed are patients', their significant others', as well as health care providers' conceptualizations of and biases regarding pain and pain control. We emphasize that it is important not only to focus on the details of the specific techniques described but also on how most effectively to present information. We note that it is important to customize any noninvasive intervention to the specific needs of the patient and their significant others. We provide some suggestions as to how this might be accomplished. Finally, we discuss some attitudes and beliefs held by health care providers that may inhibit their use of the full range of noninvasive techniques that are available for managing pain. PMID- 1286851 TI - Cancer pain: a multidimensional perspective. AB - Cancer pain has traditionally been studied from a unidimensional/medical model. However, limitations of the medical model have led researchers to the development of multidimensional models of cancer pain. The current manuscript describes a multidimensional model of cancer pain with six components: physiological, sensory, affective, cognitive, behavioral and sociocultural. Research relevant to each component of the model is reviewed with an emphasis on future research directions. PMID- 1286852 TI - Assessment of the terminally ill patient with pain: the example of cancer. AB - Efforts to understand pain associated with terminal illness have been guided traditionally by the biomedical model in which psychological and environmental factors are considered incidental and not causally significant influences of pain. More recent conceptualizations of pain, however, recognize that pain can be affected by a variety of factors including mood, beliefs about pain, past learning, as well as physical perturbations. This development has led to assessment strategies that are more comprehensive, multidimensional, and less singularly aligned with a biomedical model. The greatest amount of attention to pain among the terminally ill has focused on cancer patients. Thus, in this paper we will describe a comprehensive, multi-dimensional assessment of cancer pain. Information regarding cancer and cancer pain is first presented and then a strategy for comprehensively assessing cancer pain is outlined. Recent developments in the assessment of cancer pain are briefly reviewed. PMID- 1286853 TI - The cognitive behavioral perspective on pain management in terminal illness. AB - Cognitive Behavioral Therapy (CBT) can be an effective non-medical treatment for the alleviation of pain-related suffering in patients with advanced disease. CBT offers a common-sense theoretical model and a variety of rational and pragmatic techniques that are easy for both patients and health professionals to understand and practice. The perspective emphasizes two ideas: that pain and suffering are not the same, and that patients can exercise substantial personal control over their thoughts, feelings, and behavior. Suffering is a feeling of pervasive personal destruction, whereas pain is a sensory stimulus that does not necessarily imply general personal disintegration. CBT teaches patients to practice relaxation and active coping skills to increase pain tolerances, and to modify thoughts and attitudes that increase the perception of personal disintegration. Even in the most advanced stages of a terminal illness patients can practice these skills and experience themselves as active agents that can reduce their suffering and enhance their sense of well-being. PMID- 1286854 TI - Hypnosis and related techniques in pain management. AB - Hypnosis has been used successfully in treating cancer patients at all stages of disease and for degrees of pain. The experience of pain is influenced not only by physiological factors stemming from disease progression and oncological treatment, but also from psychosocial factors including social support and mood. Each of these influences must be considered in the successful treatment of pain. The successful use of hypnosis also depends upon the hypnotizability of patients, their particular cognitive style, their specific motivation, and level of cognitive functioning. While most patients can benefit from the use of hypnosis, less hypnotizable patients or patients with low cognitive functioning need to receive special consideration. The exercises described in this chapter can be successfully used in groups, individual sessions, and for hospice patients confined to bed. Both self-hypnosis and therapist guided hypnosis exercises are offered. PMID- 1286855 TI - On the closing of Loyola University School of Dentistry. PMID- 1286856 TI - The closing of Loyola University School of Dentistry. PMID- 1286857 TI - Mandatory continuing education to start. PMID- 1286858 TI - Will there be enough trained dental auxiliaries? PMID- 1286859 TI - Illinois dentist helps his homeland. PMID- 1286860 TI - Treating your practice like a business. PMID- 1286861 TI - How to make your retirement dreams a reality. PMID- 1286862 TI - Dyclonine hydrochloride--a topical agent for managing pain. PMID- 1286863 TI - Evolving world of health care costs. PMID- 1286864 TI - A common sense approach to practice valuation. PMID- 1286865 TI - Sjogren's syndrome. PMID- 1286866 TI - Why volunteer for dentistry. PMID- 1286867 TI - Phage display technology in antibody engineering: design of phagemid vectors and in vitro maturation systems. PMID- 1286868 TI - Theoretical and practical aspects of antigenized antibodies. PMID- 1286869 TI - Mono- and bivalent antibody fragments produced in Escherichia coli: engineering, folding and antigen binding. PMID- 1286870 TI - Engineered antibodies as pharmacological tools. AB - The ability to engineer the antibody molecule has now progressed to the stage where one can realistically contemplate creating a pharmacologically useful targeting molecule comprising a single-chain, minimal antibody combining site together with a domain that imparts a second functionality. It will certainly be possible in the near future to adjust the fine specificity and affinity of the antibody domain, either by in vitro selection methods or by site-directed mutagenesis based on structural criteria. The functional domain could be an enzyme, a toxin, or any other protein that suits a pharmacological purpose. In this review I have illustrated these directions primarily by summarizing work from my laboratory and those of my collaborators. The review covers single point mutations in the heavy chains of digoxin-specific antibodies that either strikingly diminish or strikingly enhance recognition of a small feature of the antigen, the position 12 OH moiety in the steroid nucleus. The principles for constructing a minimal, single-chain antigen-binding domain based on one of the digoxin-specific antibodies are also outlined, as are the principles for incorporating such domains into fusion proteins. Finally, as a practical application of antibody-targeted enzymes, the construction and evaluation of an anti-fibrin antibody-single-chain urokinase fusion protein is examined. This protein has enhanced potency and specificity both in vivo and in vitro, and it offers the promise of increased therapeutic efficacy as well as diminished toxicity. PMID- 1286871 TI - Building antibodies from their genes. PMID- 1286872 TI - Engineering antibodies for therapy. AB - Success in the generation of an antibody-based therapeutic requires careful consideration of the binding site, to achieve specificity and high affinity; of the effector, to produce the desired therapeutic effect; of the means of attachment of the effector to the binding site; production of the end product; and the response made by the patient to the administered compound. Each of these areas is receiving attention by antibody-engineering techniques. The number of potentially useful monoclonal antibodies developed over the last 10 years, and currently in clinical trials or preregistration, is now being increased by these engineered newcomers. It will be interesting to see over the next few years how many of these antibodies, and of which kind, emerge as products. PMID- 1286873 TI - Therapeutic human antibodies derived from PCR amplification of B-cell variable regions. AB - Despite advances in the in vitro immunization of human B cells (Borrebaeck et al. 1988) and the development of immunodeficient mice (McCune et al. 1988) for the reconstitution of the human immune system ex vivo, immortalization of antigen specific human B cells remains the limiting step in the generation of human monoclonal antibodies. Typically this is performed with the aid of Epstein-Barr virus transformation followed by subcloning, confirmation of antigen binding and hybridization of the B lymphoblasts to a suitable fusion partner such as GLI-H7. This general approach is effective and widely used; however, it is time-consuming with erratic results. These were the immediate reasons we and others devised methods to directly obtain the variable regions from small numbers of human B cells (Larrick et al. 1987). The success of the PCR-based approach is illustrated above. In the present studies we successfully captured and stably produced antibodies from the V regions of two potent human anti-tetanus antibodies secreted by heteromyelomas that were too unstable for scale-up production. Although further preclinical evaluation of these antibodies is in progress, results to date indicate that the recombinant antibodies produced in myeloma based cell lines or CHO cells are equivalent in binding specificity and activity to the native heteromyeloma-derived antibodies. Recent studies from this laboratory indicate that effective anti-tetanus protection will require a cocktail of anti-tetanus antibodies. Details of this work will be the subject of a future communication (Lang et al., in preparation). PMID- 1286874 TI - Genetically-engineered antibodies: tools for the study of diverse properties of the antibody molecule. PMID- 1286876 TI - Adjuvant arthritis pretreatment with type II collagen and Mycobacterium butyricum. AB - A treatment previous to adjuvant arthritis induction has been performed with type II collagen (CII) or Mycobacterium butyricum (Mb), which is the inducer of the pathology. Pretreatment was administered in two different ways: a) subcutaneously or intradermally 14 days before arthritis induction, and b) intravenously 3 days before induction. In order to relate the change in inflammation to the corresponding antigen immune response, serum antibodies and delayed type hypersensitivity (DTH) against CII or Mb were studied. Pretreatment with s.c. CII 14 days before induction produced slight protection against arthritis and significantly delayed its onset; systemic inflammation showed good positive correlation with anti-CII antibodies. The CII administered i.v. 3 days before arthritic challenge did not significantly modify the inflammatory process. The use of i.d. subarthritogenic doses of Mb 14 days before induction protected a high percentage of the animals from the posterior arthritic challenge; this protection was accompanied by high anti-Mb antibody titers and DTH reaction. When Mb was given i.v. 3 days before induction, a partial protection of inflammation was observed; arthritis was milder and its onset was delayed. These changes were accompanied by reduced humoral and cellular response to Mb. PMID- 1286875 TI - Auto-MHC class II-reactive T cell line obtained from MRL/+ mice suffering from lpr-GVHD. II. Analyses of functional characteristics of T cell line by in vivo administration. AB - Functional characteristics of an autoreactive (I-Ek-restricted) T cell line (l/+ T1), previously established from MRL/M(p-)+/+(MRL/+) mice with lpr-GVHD, were analyzed in vivo. Intravenous injection of l/+ T1 cells to non-irradiated H-2k (MRL/+ or AKR) mice (but not H-2d mice) induced enhanced spontaneous proliferation of recipient spleen cells; this was also I-Ek self-restricted. This augmented self-reactivity seemed to be mediated by recipient L3T4+ T cells, since few l/+ T1 cells were detected in the spleen cells of l/+ T1-injected AKR mice by cell surface marker analyses, and the treatment of the spleen cells with anti-Thy 1.1 antibody (Ab) or anti-L3T4 Ab plus complement abolished this enhanced spontaneous proliferation. The production of IgM rheumatoid factor (RF) in AKR mice and IgG RF in MRL/+ mice increased, although no enhancement of anti-ssDNA Ab production was observed. Judging from both spleen B cell proportion and serum Ig levels, autoantibody induction by the injection of l/+ T1 cells was not associated with polyclonal B cell activation. When lethally irradiated B10 congenic mice were used as recipients, B10. BR mice showed elevated levels of IgM anti-ssDNA and IgM RF 1 wk after l/+ T1 cell injection; it is likely that lethal irradiation causes autoantigens, particularly DNA, to be exposed. These findings suggest that the autoreactivity of l/+ T1 cells can be transferred to recipient L3T4+ T cells via T-T interaction or the immunological network, and that increased autoreactivity induces autoantibody production in the presence of autoantigen stimulation. In contrast to the stimulatory effects observed in AKR and MRL/+ mice, MRL/Mp-lpr/lpr(MRL/lpr) mice showed a different response to the injection of l/+ T1 cells; spontaneous proliferation of spleen cells and autoantibody production were not enhanced, and suppression of the mitogen responses was observed. It is discussed that lpr-GVHD may be due to these unusual features of MRL/lpr mice. PMID- 1286877 TI - Sensitization of allo-specific T lymphocytes in vivo: role of antigen-presenting cells. AB - The migratory behavior of antigen-presenting cells was investigated in vivo. Purified murine splenic dendritic cells and splenic and peritoneal macrophages were labelled and injected subcutaneously in the hind foot-pads of mice and monitored for seven days. In the first 24 h, a small quantity of label was recovered from popliteal but not inguinal lymph nodes with radioactive (111In oxine and 3H-uridine) but not fluorescent (1,1'-dioctadecyl 3,3,3'3' tetramethylindocarbocyanine perchlorate and fluorescein isothiocyanate) labelling of the antigen-presenting cells. Chemical fixation of the injected antigen presenting cells had no effect on the detection of label in the popliteal lymph nodes, suggesting that it was unlikely to be due to active cellular migration. Label recovery from hind feet declined with time over the seven day period and was independent of the label type. Essentially the same observations were made whether the antigen-presenting cells were syngeneic or allogeneic to the injected mice and irrespective of the type of antigen-presenting cell used. However, allogeneic antigen-presenting cells, which did not migrate to the draining lymph nodes, successfully primed T lymphocytes in these lymph nodes as shown by a secondary in vitro mixed leukocyte reaction. Again, chemical fixation of the injected antigen-presenting cells had no effect on their ability to prime allogeneic T lymphocytes in the draining lymph nodes. These experiments suggest that, during experimental allo-sensitization via the subcutaneous route, indirect priming of allogeneic T lymphocytes may be a dominant pathway. PMID- 1286878 TI - Immunosuppressive effects induced by the polysaccharide moiety of some bacterial lipopolysaccharides. AB - The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization resulted in a significant increase in the antibody response. Such enhancement may be due mainly to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed; however, B cell mitogenicity of the LPS molecule also may be involved. By contrast, treatment with LPS at the time of immunization with SSS-III induces significant suppression of the SSS-III-specific antibody response; such suppression is not induced by LPS or lipid A derived from Escherichia coli and Salmonella minnesota, and is independent of the capacity of LPS to activate B cells polyclonally, an activity generally attributed to the lipid A fraction of LPS. Studies conducted with the LPS of P. aeruginosa indicated that the suppression induced is T cell dependent and mediated by the polysaccharide (PS) fraction of LPS; it appears to be due-at least in part-to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. The significance of these findings to the pathogenesis of certain gram negative infections is discussed. PMID- 1286879 TI - The influence of dietary fat on the interaction of lymphocytes with high endothelial venules. AB - The specific adherence of lymphocytes to high endothelial venules (HEV) represents the first step in the lymphocyte emigration from blood into most lymphoid tissues. The interaction of lymphocytes with HEV exhibits a remarkable organ specificity, which appears to be mediated by complementary receptors on both recirculating lymphocytes (homing receptors) and tissue-specific HEV (vascular addressins). The expression of homing receptors varies and depends on factors such as lymphocyte subtype, stage of activation and maturation. As these receptors are glycoproteins, which are anchored in the cell membrane, it can be envisaged that their position and function are determined by the overall composition of the cell membrane itself. In this study we investigated the significance of dietary fat concentration and saturation for the interaction between lymphocytes and HEV. In addition to these functional studies, the expression of homing receptors in combination with T and B cell markers were analyzed. Using immunohistochemistry the effect on the presence and characteristics of lymphocytes and HEV in situ was studied. Changes in the dietary fatty acid composition resulted in an altered ability of T and B cells to adhere to HEV, without affecting their binding preference. The changed adhesion patterns seemed to be associated with alterations in the expression of adhesion molecules, that are essential for the lymphocyte migration. The latter observation might in turn be explained by the observed modifications in the fatty acid composition of the lymphocytes. These results suggest a role for the fatty acid composition of the nutrition in the process of lymphocyte recirculation. PMID- 1286880 TI - Enhancement of antigen-specific activation of CD8+ memory cytotoxic T cells by B cell-derived factors. AB - Purified CD8+ T cells from influenza A/WSN-immune BALB/c (H-2d) mice respond with the generation of secondary A/WSN-specific Tc cells in vitro when stimulated with a synthetic peptide (NPP) with a sequence derived from influenza A virus nucleoprotein with high affinity for Kd class I MHC molecules. The process of the conversion of NPP-Kd-responding Tc cell precursors into effector Tc cells in a population of CD8+ T cells occurs with no demonstrable requirements for accessory cells or their lymphokine products. The addition of culture supernatants from several mouse and human B cell lymphomas and LPS-activated normal mouse B cells to the culture of NPP-stimulated immune CD8+ T cells enhanced the induction of secondary Ag-specific Tc cells. None of the tested supernatants in the absence of Ag (NPP) induced cytolytic Tc cells, indicating that B cell-derived secretory factors can exert their activity only on Ag-exposed CD8+ T cells. The augmentatory effect of these supernatants on Ag-specific activation of memory CD8+ T cells was attributed to the synergism between B cell-derived factors and IL-2 which is produced endogenously in cultures of NPP-stimulated D8+ T cells. The possible role of B cell-derived helper factors is discussed. PMID- 1286881 TI - Rat thymic epithelium positively selects mouse T cells with specificity for rat MHC class II antigens but fails to induce detectable tolerance in the mouse T cells to the rat MHC antigens. AB - BALB/c (H-2d) nude mice were grafted with allogeneic AKR/J (H-2k) or xenogeneic (ACI-N rat, RT1av1) fetal thymuses which were depleted of hemopoietic cells by incubating with 2'-deoxyguanosine (2'dGuo) in vitro prior to grafting. The nylon wool-passed LN T cells from nude mice grafted with 2'dGuo-treated AKR/J thymus showed a poor proliferative response to B10BR (H-2k) stimulator cells, confirming that mouse thymic epithelium has the capacity to induce tolerance against the mouse MHC antigens on the thymic epithelium. On the other hand, the nylon-wool passed LN T cells from nude mice grafted with untreated or 2'dGuo-treated ACI/N rat thymus showed significant proliferative responses to ACI/N, which can be blocked by anti-rat MHC class II mAb, whereas the nylon-wool-passed LN T cells from nude mice grafted with syngeneic thymus hardly responded to the xenogeneic stimulator cells. These results suggest that rat thymic stromal cells including thymic epithelium can not induce detectable tolerance in mouse T cells to rat MHC antigens; but rat thymic epithelium may positively select mouse T cells with specificity for rat MHC class II antigens, resulting in a mouse T cell repertoire with strong xeno-reactivity. PMID- 1286882 TI - Cytokine production by murine cells activated by erythrogenic toxin type A superantigen of Streptococcus pyogenes. AB - The mode of pathogenic action of the Steptococcus pyogenes superantigen erythrogenic toxin type A (ETA) in causing toxic shock-like syndrome in humans is thought to be mediated by massive release of cytokines by patients immune cells. The cytokine-inducing capacity of ETA as an extracellular protein was compared with that of lipopolysaccharide (LPS), a component of cell wall of gram-negative bacteria. Peritoneal macrophages and splenocytes of BALB/c and C3H/HeJ mice were stimulated by ETA and LPS. Tumor necrosis factor (TNF), interleukin 3 (IL-3) and interleukin 6 (IL-6) activities in the supernatants of stimulated cells were evaluated. In contrast to LPS, ETA induced only low amounts of IL-6 and no detectable TNF activities in peritoneal macrophage supernatants. ETA-triggered BALB/c and C3H/HeJ splenocytes produced great amounts of IL-6. ETA triggered the production of IL-3 by both mice strains splenocytes in a dose dependent manner. The amounts of IL-3 in supernatants were comparable to those induced by concanavalin A. The simultaneous presence of ETA and LPS in macrophage and splenocyte cultures induced a slight enhancement above an additive value after 72 96 h. Challenge of BALB/c mice with ETA 6 h before the harvest of peritoneal macrophages led to an enhanced production of IL-6 upon stimulation with ETA as well as with LPS. Splenocytes of nude BALB/c mice did not produce IL-6 upon stimulation with ETA, whereas LPS-induced IL-6 production was similar in these mice and in their littermates. The pathogenic effect of ETA on host's immune cells could most likely be explained as a consequence of T cell activation. The results confirm also that LPS- and ETA-induced shock is mediated by different cell types. PMID- 1286884 TI - International classification of rodent tumours. Part I--The rat. 2. Soft tissue and musculoskeletal system. PMID- 1286883 TI - Functional analyses of lpr gene in MRL/Mp-lpr/lpr mice. Role of lymph node stromal cells in lpr-lymphadenopathy. AB - To clarify the mechanism by which the lpr gene causes lymphadenopathy, we established an experimental system to induce lymph node (LN) swelling in unaffected mice. In MRL-(+)/+ mice that had been 5 Gy-irradiated and grafted with bone marrow cells (BMCs) plus LN from MRL-lpr/lpr mice, a remarkable enlargement of the LN grafts was seen. The enlarged grafts lacked normal LN structure and were indistinguishable from LNs of MRL-lpr/lpr mice. The induction of LN swelling by this method was achieved not only in [MRL-lpr/lpr-->MRL-(+)/+] but also in [MRL-lpr/lpr-->BALB/c], [MRL-lpr/lpr-->C3H], [B6-lpr/lpr-->B10.Thy1.1], and [B6 lpr/lpr-->BALB/c] combinations. Furthermore, the lpr/lpr LN grafts developed lymph node swelling even without the transplantation of BMCs. Most cells in the grafted LNs disappeared within a few days, and large clear fibroblast-like cells then became dominant for 1 to 4 weeks. Thereafter, lymphoid cells increased and had filled the graft by the 8th week. The LN grafts obtained from MRL-lpr/lpr (but not MRL-(+)/+) mice showed the ability to transfer LN node swelling into the secondary MRL-(+)/+ hosts two weeks after the primary transplantation. These results strongly suggest that the fibroblast-like LN stromal cells play a crucial role in lpr-associated lymphadenopathy. PMID- 1286885 TI - Assessment of child growth: some basic issues. PMID- 1286886 TI - Physical and sexual growth pattern of affluent Indian children from 5 to 18 years of age. AB - The present study was conducted to study growth parameters on 12,899 boys and 9,951 girls of affluent class from 8 States of the country. In pooled data, the 50th centile height approached 30-40th centile till 6 1/2 years in boys and up to 10 years in girls, and ultimately the height growth curves for both fell between the 10-20th centile of NCHS standards. Similarly, for weight, they approached 10 20th centile of NCHS at the age of 17 yr. Comparison with other European countries showed that Indian affluents are shorter and lighter; however, they are similar to their counterparts of Asian origin. The secular trend for height in Delhi showed increase of 2.1 cm for boys, and 2.7 cm for girls per decade at 17 yr and 14 yr, respectively. In Varanasi, the corresponding trend was 1.5 and 2.1 cm at 16 yr for boys and girls, respectively. The mean ages for genital development stages G 2-5 were 11.9, 13.3, 14.6 and 15.9 yr; respectively. In girls, the breast development Stages B 2-5 had mean ages of 10.9, 12.8, 13.9 and 14.8 yr, respectively. The mean age for menarche was 12.6 yr. In 14 yr old boys, the mean height may vary between 150.3, 155.8, 161.2 and 165.2 cm and mean weight between 38.0, 42.5, 46.8 and 52.9 kg for genital stages G 2-5, respectively. Similarly, girls of 12.5 yr (close to menarcheal age of 12.6 yr) had mean height 145.3, 150.3, 152.1 and 153.8 cm and mean weight 34.7, 41.2, 45.4 and 54.4 kg for breast stages B 2-5, respectively. It is recommended that for growth assessment during adolescence these charts in relation to sexual development and age be used for comparison. PMID- 1286887 TI - Bacteremia and bacterial infections in highly febrile children without apparent focus. AB - To find the incidence of bacteremia and serious bacterial infections in febrile children without an apparent focus of infection, we prospectively studied 100 febrile children aged 1 month-3 years with a rectal temperature > or = 39 degrees C. Ten children had a blood culture positive bacteremia and nine had serology positive for bacteremia; 6 had urinary tract infection, 5 otitis media and 8 meningitis. A diagnosis of non bacterial illness was made in 62 patients. Staphylococcus aureus was the most common bacteriologic isolate on blood culture (five) and by serology (eight). TLC > or = 15,000/cu mm m-ESR > or = 25 mm and temperature > or = 39 degrees C had high specificity (95-100%) but low sensitivity for diagnosis of bacteremia. PMID- 1286888 TI - Appendicitis in the newborns. PMID- 1286889 TI - Congenital cleft foot (lobster claw): an unusual association with ano-rectal malformation. PMID- 1286890 TI - Poland syndrome with dextrocardia. PMID- 1286891 TI - Celiac disease in insulin dependent diabetes mellitus. PMID- 1286892 TI - Lethal multiple pterygium syndrome. PMID- 1286893 TI - Myositis ossificans progressiva. PMID- 1286894 TI - Improvised warm rooms for newborn care. PMID- 1286895 TI - Red man syndrome. PMID- 1286896 TI - Cardiovascular complications of enteric fever. PMID- 1286897 TI - Zinc and magnesium in pediatric practice. PMID- 1286898 TI - Triage of war wounded: the experience of the International Committee of the Red Cross. AB - The hospitals of the International Committee of the Red Cross are often faced with situations in which the number of war wounded requiring surgical attention overwhelms the available facilities. Hospital organization, equipment and changes of attitude necessary for health professionals are considered with respect to triage. Practical aspects of assessment and categorization of the wounded are considered in the light of a large experience; relocation and reassessment of those who do not warrant immediate surgery benefit patients and hospital staff alike. The importance of adherence to an emergency plan and respect for the decisions of the person in charge of the triage are emphasized. The difficult and stressful nature of triage of war wounded should always be taken into account. PMID- 1286899 TI - TRISS analysis of trauma care: a Yugoslav perspective. AB - The TRISS method has been claimed to be useful in the evaluation of trauma care. The aim of this study was to compare our data with Major Trauma Outcome Study (MTOS) results in North America, and to note differences and strive to improve care in our system. Data were collected from 163 consecutively admitted trauma patients to the Intensive Care Unit, Accident and Emergency Centre, Belgrade, Yugoslavia. Systolic blood pressure, respiration rate and Glasgow Coma Score were obtained on admission and the Abbreviated Injury Score was presented by anatomical area. Data were analysed on an Amstrad PCW computer, using a special non-commercial program. The calculated expected survival out of 163 cases was 131.7 and observed 111 patients. Distribution of severity of injury of the study population had a greater severity of injury than did the baseline. Thus, although the observed survival was less than expected, this is not conclusive evidence of worse care. This applies especially to the group of patients over 54 years of age who suffered blunt trauma, whose higher mortality (23 observed and 15.6 expected out of 50 patients) can be attributed to the ISS score being almost double that of the MTOS population of comparable age. Penetrating trauma patients, in spite of severe injuries, had better survival than predicted. The TRISS method, in spite of its limitations, proved a useful method of evaluating trauma care, and can be run on a small computer without the necessity for special staff. PMID- 1286900 TI - The perioperative care of orthopaedic and trauma patients in a high-dependency unit: a 2-year prospective audit. AB - There is an increasing trend towards the establishment of high-dependency units in large hospitals since it is thought that they conveniently 'fill the gap' between the intensive care unit and the routine wards. This paper prospectively reviews the results of management of 205 orthopaedic and trauma patients who passed through such a unit over a 2-year period. The unit was shown to provide effective and safe care for a group of particularly high-risk patients for whom care on a routine ward at times would be insufficient and for whom care on an intensive care unit is unnecessarily expensive and occasionally unavailable. The high-dependency unit as described in this paper represents an efficient use of resources for this group of patients. PMID- 1286901 TI - Justification for evacuating acute subdural haematomas in patients above the age of 75 years. AB - The author has reviewed the outcome of 27 patients aged 75 years and over who had an operation for acute traumatic subdural haematoma at Frenchay Hospital, Bristol, over a 10-year period. There were 15 men and 12 women with a mean age of 79.2 years. The outcome at 6 months was determined using the Glasgow Outcome Score. Of the patients, 15 per cent made a good recovery, 15 per cent a poor recovery and 70 per cent died. The influence of age, sex, mechanism of injury, preoperative Glasgow Coma Score (GCS), pupillary reactivity to light, skull and limb fractures, clinical course, CT scan appearance and timing of operation were analysed in relation to the outcome. The results showed that a preoperative GCS of 4 or less and unilateral pupillary dilatation and non-reactivity to light were not compatible with good survival in the very elderly patient with acute subdural haematoma. Under these circumstances, operation is not justified. The prognosis was worse in patients who were unconscious immediately after injury and with a CT scan showing a subdural haematoma and a haemorrhagic contusion which required urgent early intervention. The prognostic indicators present may prove useful in the selection of patients for active surgical intervention. PMID- 1286902 TI - Internal fixation or arthroplasty for displaced subcapital fractures in the elderly? AB - A series of 200 patients aged over 69 years admitted to this hospital with a non pathological displaced subcapital fracture of the femur, have been studied prospectively. Approximately one-half were treated by internal fixation and the remainder by a hemiarthroplasty, the method of treatment being dictated by the preference of the on-call consultant. This has enabled a comparison between the two groups. At 1 year from injury there was no significant difference in the mortality or function of the survivors. Internal fixation resulted in fewer postoperative complications, a shorter hospital stay and a reduced cost of treatment. The reoperation rate for internal fixation was three times that after hemiarthroplasty. Despite the problem of non-union, this study suggests that internal fixation is the treatment of choice for displaced subcapital fractures in the elderly. PMID- 1286903 TI - The monofixator in the primary stabilization of femoral shaft fractures in multiply-injured patients. AB - In multiply-injured patients with femoral shaft fractures, evidence grows that a fast primary temporary stabilization device is preferable to a definitive method of stabilization by intramedullary nailing or plate osteosynthesis. Conversion to intramedullary nailing is performed later. During a 16-month period, we treated nine patients with 10 femoral shaft fractures in this way. There were two open fractures and six other fractures were associated with severe soft tissue damage. The overall function result is excellent and consolidation was reached after a relatively short time. The advantages are clear: a shorter operation time, earlier mobilization and rehabilitation, and fewer complications. PMID- 1286904 TI - Long-term prognosis of displaced Colles' fracture: a 10-year prospective review. AB - In all, 85 per cent of Colles' fractures are clinically satisfactory after 10 years. Clinical results improve little after 3 months. Displaced intraarticular fracture, wrist deformity and algodystrophy are associated with an unsatisfactory outcome. PMID- 1286905 TI - Does plaster immobilization predispose to pulmonary embolism? AB - Over a 5-year study period, 22 patients with isolated lower limb injuries who were immobilized in a plaster cast developed a pulmonary embolus. This information was not available from orthopaedic audit. Better cross-specialty accounting is required if complications that span different hospital specialties are to be fully elucidated. This problem was heightened by the number of emboli occurring while the patient was being treated as an outpatient. PMID- 1286906 TI - Isolated sternal fracture: a benign injury? AB - Since seat belt legislation was introduced in this country in 1983, we have seen an increasing number of patients admitted to our unit for observation following seat belt related sternal fractures. In order to determine the value of routine admission of patients with isolated sternal fracture we have reviewed a series of 104 consecutive patients admitted between February 1983 and February 1990 with this injury. Of these, 90 were sustained in road accidents, 79 of which were as a consequence of seat belt use. The average age of these patients was 54.5 years (range 11-85 years) with an average duration of hospital stay of 2.9 nights. No serious complications were observed. These findings suggest that there may be no need to admit these patients solely for observation if their initial clinical condition is satisfactory and there are no abnormalities identified by an anteroposterior chest radiograph and electrocardiography. PMID- 1286908 TI - When should a synthetic casting material be used in preference to plaster-of Paris? A cost analysis and guidance for casting departments. AB - An accurate cost analysis of the use of one of the new synthetic casting materials (Cellacast) compared with plaster-of-Paris (Gypsona) was undertaken over a 3-month period in the fracture clinic of Cardiff Royal Infirmary. The mean duration of usage before failure for synthetic forearm, scaphoid and below-knee casts was found to be approximately twice that of plaster casts. The use of synthetic casting materials was found to be cost-effective in situations where there was thought to be a high probability that structural failure of the cast would occur. Guidelines for the use of plaster-of-Paris and synthetic casting materials are presented. PMID- 1286907 TI - Emergency laparotomy for abdominal trauma. AB - We have retrospectively reviewed our experience of 153 consecutive patients who underwent emergency laparotomy for suspected intraabdominal injury over a 10-year period. The commonest cause of injury was road traffic accidents (61 per cent), and the commonest indication for operation was signs of peritoneal irritation (35 per cent). Peritoneal lavage was performed in 62 patients (41 per cent). The liver was the organ most frequently injured (52 patients, 34 per cent) and 52 per cent of these patients died. Splenic injuries occurred in 46 patients (30 per cent). The negative laparotomy rate was 16 per cent. Forty-five patients died (29 per cent) and five of these had negative laparotomies. The Injury Severity Score (ISS) of all patients who died was > 16. PMID- 1286909 TI - Musculoskeletal injuries in the Afghan war. AB - Among the 1274 patients admitted to a Pakistan border hospital from 1985 to 1987, the distribution and outcome of musculoskeletal war injuries differed from those seen in other conflicts. Serious complications from injuries were found in approximately 50 per cent of patients, of which most were wound infections, chronic osteomyelitis, and restriction of joint motion. Guerrillas in the Afghan war had no access to acute medical treatment in the field. Many patients died before reaching the hospital, as reflected in the low proportion of paraxial injuries; very high complication rates were noted for all injuries. Although some complications, such as soft tissue infection and foreign body retention are not site specific, other complications such as contracture, non-union, loss of range of motion, and chronic osteomyelitis are highly related to the region injured. Early surgical management and evacuation of those with musculoskeletal war injuries can greatly improve the outcome from war trauma and reduce the subsequent disability. However, the increasing use of hand-held anti-aircraft missiles may prevent the rapid evacuation of the wounded in future conflicts, and may make the situation seen in Afghanistan more common. PMID- 1286910 TI - The role of tissue pressure recording in forearm fractures in children. AB - During a 25-month period, 15 children with severe forearm fractures had signs and symptoms suggestive of an early compartment syndrome and underwent tissue pressure measurements. Of these, seven were found to have elevated intracompartmental pressures and had decompressive fasciotomies performed. The remaining eight patients had normal pressures and subsequently made uneventful recoveries. Tissue pressure recording is a useful adjunct to clinical diagnosis in suspicious cases of compartment syndrome, particularly in children. PMID- 1286911 TI - Meniscal suture: a simple method. AB - A simple technique of meniscal suture is described. It avoids the main problem with most other outside-to-inside suture techniques, which is that knots either have to be left inside the joint or have to be pulled out through the meniscus. These knots often come undone or damage either the joint surface or meniscus. Essentially, a suture is inserted from outside to inside through the meniscus, using a cannulated needle. The end of this suture is then pulled back out through a separate hole in the meniscus, using a suture loop inserted with another cannulated needle. The two ends of the first suture are then tied together. PMID- 1286912 TI - Unnecessary arthroscopies. AB - A review of the results of arthroscopies on patients taken from an 'open access' service waiting list has been carried out. One-third of all arthroscopies proved to be negative. Accuracy of clinical diagnosis was not related to the clinical grade of the examining doctor. The excess annual cost to the Northern Ireland Orthopaedic Service of unnecessary arthroscopies may have been of the order of 89,000 pounds. PMID- 1286913 TI - Control of life-threatening haemorrhage from the neck: a new indication for balloon tamponade. AB - We report the use of a Foley catheter, placed through the wound, to provide balloon tamponade of major bleeding from the neck and supraclavicular fossae. In 10 consecutive explorations for exsanguinating injury in these regions balloon tamponade was used eight times, and was judged to be fully effective in four patients, partly effective in one, and ineffective in three patients. PMID- 1286914 TI - Spiral fracture of the proximal phalanx of the index finger by finger wrestling. PMID- 1286915 TI - Venous bullet embolism: a case report and review of the literature. PMID- 1286916 TI - Retrosternal dislocation of the clavicle: the 'stealth' dislocation. PMID- 1286917 TI - Posterior sternoclavicular dislocation: a novel method of external fixation. PMID- 1286918 TI - The drain sleeve. PMID- 1286919 TI - Mechanical properties of the Pinless external fixator on human tibiae. AB - In the treatment of either acute severe open tibial fractures or their sequelae, a convenient external fixator is desirable. The conventional transosseous fixation with pins entering the medullary cavity is associated with problems such as pin loosening and pin track infection. Due to the bacterial contamination of the medullary space via the pin track the change of treatment from primary external fixation to secondary medullary nailing is an infection risk. In order to minimize these problems an external clamp fixator, the Pinless, was created. Medullary penetration is avoided by substitution of the conventional pins with clamps. The latter are inserted by hand (removable handles) and anchored only in the bone cortex. The medullary cavity stays intact. But is this clamp fixation stable enough for clinical use? MATERIAL AND METHODS: On paired human cadaver tibiae, we compared the mechanical properties of the experimental Pinless, the conventional AO-tubular fixator and the Ultra-X fixator. Clamps differing in size (small/large) and material (steel/titanium) were used and compared to Schanz screws (steel, 5.0 mm diameter). We measured the stiffness of comparable configurations (1 or 2 bars) under axial compression, four-point-bending in two planes, and torsion. The pull-out force of the different clamps in relation to the bone diameter and number of rocking movements during insertion was also determined. RESULTS: The Pinless configurations with small clamps and 1 bar showed stiffness values as follows (as a percentage of the corresponding AO tubular fixator): 42/36% (steel/titanium clamp) axial stiffness, 61/43% bending stiffness perpendicular to the reference plane, 78/79% bending stiffness parallel to the reference plane, and 90/95% torsional stiffness. The corresponding Ultra-X device was not as stiff as the Pinless. The use of two longitudinal rods increased the relative stiffness only under axial compression. The mean pull-out force on the proximal tibia was 1011 N for the small steel clamp, 717 N for the large steel clamp, 681 N for the small and 777 N for the large titanium clamp. At the lowest tibial diameter the values were reduced by 10 to 43%. The rocking movements doubled the pull-out force, e.g. there was a pull-out force for the large clamp of 600 N with five rocking movements compared to 310 N without. DISCUSSION: The Pinless was not as stiff as the conventional AO-tubular device but stiffer than the clinically used Ultra-X, especially in sagittal bending, the main load on a tibial fracture in the first weeks after trauma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1286920 TI - The development of the Pinless external fixator: from the idea to the implant. PMID- 1286921 TI - "Pinless" calcaneus traction. PMID- 1286922 TI - Stable temporary traction substitute with the Pinless external fixator. AB - The stable traction substitute with a JBPF seems a very promising indication for pinless clamps, offering good patient comfort and easy care. The implantation of a JBPF is possible under the same conditions as for conventional calcaneal traction. Although the stability provided is less than for conventional external fixators, it is sufficient for a temporary traction device. The JBPF does not affect secondary ORIF. PMID- 1286923 TI - Biomechanical evaluation of the Pinless external fixator. AB - In open fractures especially in those with severe soft tissue damage, fracture stabilisation is best achieved by using external fixators. There are some intrinsic complications which occur during classical external pin fixation. To overcome the problem of pin track infection and vascular damage from drilling, the Pinless external fixator was developed. It is based on the idea of a forceps with trocar points, which only penetrate the bone cortex superficially. The function of the device was tested in two mechanical trials and two in vitro tests in which one pinless clamp was put under a controlled load of 50 N, 150 cycles/day and studied over a 5 week period in sheep. The loads and time range of the experiment were chosen to simulate a temporary fracture stabilisation in a patient not bearing weight. The main question to be answered was whether the Pinless external fixator would be able to maintain stable fixation. Furthermore, it was to determine the changes at the trocar-to-bone interface. The clamp was found to maintain 72% of the initially applied clamping force after 5 weeks of in vivo application and it was found to be tight at removal. Some decrease of clamping force was found during the first 20 days and then the force tended to level off. There was no slippage nor did the clamp penetrate the cortex. There were no obvious signs of infection around the trocar-holes and in the bacterial tests no pathological cultures were grown. Histology revealed very localised bone reactions, the indentation caused by the trocar tips being only 1.2 mm deep. The study concludes, as far as could be ascertained from these tests, that it is safe to use pinless external fixation for temporary fracture fixation. PMID- 1286924 TI - A review of the developmental defects of enamel index (DDE Index). Commission on Oral Health, Research & Epidemiology. Report of an FDI Working Group. PMID- 1286925 TI - Realistic standards for quality assurance. AB - Standards are playing an increasingly important role in the field of quality assurance for dental and laboratory working conditions and performances. Evaluation, in terms of characteristics and importance, varies with the individual position and views of the respective institutions and authors but realistic standards are required to implement meaningful quality assurance measures. PMID- 1286926 TI - The Periotest method. AB - The Periotest is a new instrument for the diagnosis of periodontal diseases. The 'Periotest value' depends to some extent on tooth mobility, but mainly on the damping characteristics of the periodontium. The Periotest measures the reaction to a reproducible impact applied to the tooth crown. The Periotest value is a biophysical parameter. PMID- 1286927 TI - CPITN assessment of periodontal treatment needs in the population of Zagreb, Croatia. AB - The aim of this study was to assess the prevalence and required treatment of periodontal disease in Zagreb using the CPITN system. A total of 3176 subjects of both sexes, divided into reference age groups, was studied using the methods and standards recommended by the World Health Organization, the Community Periodontal Index of Treatment Needs (CPITN). A very high prevalence of periodontal disease in the population of Zagreb was recorded. Gingivitis was found in the entire population of school children and deep pockets were present even in those aged 20 years, the prevalence progressively rising with age. The need for oral hygiene instruction was recorded in almost all subjects examined, and the highest need for specialist periodontal treatment was registered in more than 56 per cent of the oldest subjects, over the age of 64. The data suggests the need for better organisation of preventive services and a more conscientious approach to treatment. PMID- 1286929 TI - Dental hygiene practice: international profile and future directions. AB - Results of an international survey on dental hygiene are reported. The survey was conducted in 1988 through the International Dental Hygienists' Federation as part of a project to establish and maintain an international database on the profession. Information was collected by mail from national dental hygienist associations, using a 40-item questionnaire developed for the purpose; preliminary tabulations were validated by the associations. Information is presented for 13 countries-Australia, Canada, Denmark, Italy, Japan, Korea, The Netherlands, Nigeria, Norway, Sweden, Switzerland, the United States and the United Kingdom. Characteristics include historical development, numbers and distribution, education, regulation, scope of practice, employment settings and conditions, professional organisation, and perceived oral health and professional issues. The profiles and issues are examined in the light of broader socio economic, demographic, epidemiological, technological and policy-related trends and changes. Implications for future health and organisational planning are noted. PMID- 1286928 TI - Dental health of children in an integrated urban development programme for destitute mothers with twins in Addis Ababa. AB - The Ethiopian Gemini Trust in Addis Ababa is a charitable organisation which cares for mothers who have delivered twins or triplets. A dental preventive programme for the disadvantaged children in the Trust was begun and this paper describes the first objective of the programme, the determination of the levels of dental disease. Caries, periodontal disease, malocclusion and enamel opacities were recorded. PMID- 1286930 TI - The effects on flying and diving personnel of drugs used in dental practice. Commission on Defence Forces Dental Services. Report of an FDI Working Group. PMID- 1286931 TI - Structural variations in the crystal structures of two homologous DL-Leu and delta-Leu containing peptides. AB - The similar conformations and interaction modes of Ac-DL-Leu-NMe2 and Ac-delta Leu-NMe2 molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the alpha, beta-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to alpha, beta-unsaturation, with a small shortening by 0.04 A and 0.02 A of the N--C alpha and C alpha--C' bonds, respectively, and an increase by 6 degrees of the N--C alpha--C' bond angle. The ethylenic and amide groups in the delta-Leu derivative are far from coplanarity, and a significant electronic conjugation of the pi-orbital is likely to be rejected. PMID- 1286933 TI - Design, construction and application of a fully automated equimolar peptide mixture synthesizer. AB - A fully automated peptide synthesizer has been constructed that is capable of the synthesis of equimolar peptide mixtures and the simultaneous synthesis of 36 individual peptides. The synthesizer was constructed from a workstation of our own design utilizing a Zymark robot arm. A Macintosh II computer coordinates the movements of the robotic arm, the switching of over 40 solenoid valves and the monitoring of sensors in the workstation. The robot hands are used to deliver solvents from pressurized spigot lines and to pipet amino acid solutions from reservoirs to an array of reaction vessels. Liquid dispensing, reagent mixing and solvent removal are controlled from a multifunction I/O board in the computer. The design features of the synthesizer are presented, as well as the characterization of multiple individual peptides, a simple mixture of 19 components, and a complex mixture of 15,625 components. PMID- 1286932 TI - Solid phase peptide synthesis on hydrophilic supports. Part II--Studies using Perloza beaded cellulose. AB - Beaded cellulose (Perloza) was modified with acrylonitrile followed by reduction with diborane to give a functionalised support containing aminopropyl groups. This spacer arm was then further extended with a glycolamido or an Fmoc-amino acid-4-oxymethylphenoxyacetyl moiety. A number of peptides, including the Merrifield test peptide leucyl-alanyl-glycyl-valine, leucine-enkephalin, Acyl Carrier Protein (65-74), angiotensin I and II, ACTH(4-11) and LHRH were synthesised on the aminopropyl beaded cellulose support using modified t butyloxycarbonyl (Boc) or fluorenylmethoxycarbonyl (Fmoc) synthesis protocols. The peptides were cleaved from the support and further purified. PMID- 1286934 TI - Synthesis and characterization of defensin NP-1. AB - Defensins are a group of small, cationic, antimicrobial proteins found in the cytoplasmic granules of neutrophils and macrophages of a variety of mammalian species. One such defensin, NP-1, isolated from rabbit neutrophils, has been shown to consist of 33 amino acids rich in arginine and cysteine residues. We have synthesized NP-1 on an Applied Biosystems Model 431A peptide synthesizer using FastMoc chemistry involving HBtu [2-1H-benzotriazol-1-yl)-1,1,3,3 tetramethyluronium hexafluorophosphate] activation for coupling amino acids. The linear peptide was folded by air oxidation to the biologically active form containing three disulfide bonds and purified by reverse phase chromatography. The amino acid sequence of the synthetic peptide was confirmed by Edman degradation. Molecular weight determination by plasma desorption mass spectroscopy (PDMS) gave a value of 3898.6, in agreement with the expected molecular weight of 3898. The biological activity of the synthetic peptide, as measured by its antifungal activity against several pathogenic fungi, was indistinguishable from that of the natural NP-1. Also, the CD spectrum was equivalent to that of natural NP-1, indicating conformational identity of the two species. PMID- 1286935 TI - Solution conformation of endothelin and point mutants by nuclear magnetic resonance spectroscopy. AB - Two-dimensional NMR techniques were utilized to determine the secondary structural elements of endothelin-1 (ET-1), a potent vasoconstrictor peptide, and two of its point mutants, Met-7 to Ala-7 (ETM7A), and Asp-8 to Ala-8 (ETD8A) in acetic acid-d3/water solution. Sequence specific NMR assignments were determined for all three peptides, as well as chemical shifts and NOE connectivity patterns. The chemical shifts of ET-1 and ETM7A are identical (+/- 0.05 ppm) except for the site of substitution, whereas marked shift changes were detected between ET-1 and ETD8A. These chemical shift differences imply that the Asp-8 to Ala-8 mutation has induced a conformational change relative to the parent conformation. All three molecules show the same basic nuclear Overhauser effect (NOE) pattern, which suggests that the gross conformation of all three molecules is the same. Small changes in sequential NOE intensities and changes in medium-range NOE patterns indicate that there are subtle conformational differences between ET-1 and ETD8A. PMID- 1286936 TI - Conformational investigation of alpha,beta-dehydropeptides. Part. IV. Beta-turn in saturated and alpha,beta-unsaturated peptides Ac-Pro-Xaa-NHCH3: NMR and IR studies. AB - Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa NHCH3 and heterochiral Ac-Pro-D-Xaa-NHCH3 (Xaa = Val, Phe, Leu, Abu, Ala) as well as alpha,beta-unsaturated Ac-Pro-delta Xaa-NHCH3 [delta Xaa = delta Val, (Z) delta Phe, (Z)-delta Leu, (Z)-delta Abu] were investigated in CDCl3 and CH2Cl2 by 1H-, 13C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts delta delta for NH (Xaa) and NHCH3 on going from CDCl3 to (CD3)2SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and alpha,beta-dehydropeptides (delta Xaa) on the other. Former compounds are conformationally flexible with an inverse gamma-bend, a beta-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and alpha,beta-dehydropeptides are very similar, with the type-II beta-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The beta-turn formation propensity seems to be somewhat greater in alpha,beta-unsaturated than in heterochiral peptides, but an estimation of beta-folded conformers is risky. PMID- 1286937 TI - HPLC and PDMS analysis of cleavage products aid in the design of small, stable ANP analogues. AB - The degradation of a prototypical small analogue of atrial natriuretic peptide (ANP) has been studied using HPLC and mass spectrometric techniques. These studies revealed that removal of the N-terminal amino acid was the primary catabolic event in vitro. Based on this information the N-terminus was remanufactured to provide a family of more stable analogues. Additional stabilization was provided through modification of the C-terminal tripeptide. Through dramatically more stable in vitro, these new analogues do not appear to have longer in vivo half-lives. PMID- 1286938 TI - Hydrogen fluoride catalyzed migration of side chain protecting groups onto Fmoc during solid phase peptide synthesis. Characterization by CF-FAB analysis of carboxypeptidase digestions and NMR spectroscopy. AB - The solid-phase synthesis of the N alpha-Fmoc analog of protein kinase C substrate (PKCS, Lys-Arg-Ala-Lys-Ala-Lys-Thr-Thr-Lys-Lys-Arg) was characterized by low recovery from the resin and the concomitant appearance of four impurities. FAB-MS revealed molecular weights for two of these impurities that corresponded to the desired peptide plus Tos or Bzl. The other two were justified by invoking a CO2 elimination of the Clz protecting group to yield: 1) peptide plus 2 chlorobenzyl (ClBzl) and 2) peptide plus ClBzl and Tos. A CF-FAB analysis of carboxypeptidase digestions allowed observation of peptide cleavage down to an ion corresponding to lysine, Fmoc, and the corresponding protecting group(s). These data revealed that the impurities were not the result of incomplete deprotection but the result of migration of the protecting groups to the N terminal end of the peptide. NMR experiments were subsequently performed and revealed the exact site of substitution: the meta positions of the N-terminal Fmoc. These impurities are presumed to arise by electrophilic aromatic substitution of the fluorene group during HF treatment. The desired Fmoc analog served as a convenient, albeit low-yielding, intermediate for purification of the highly charged PKCS by preparative self-displacement HPLC. PMID- 1286939 TI - Mass balance strategy for protein sequencing. Application to a protein with an extended DNPNNP repeating motif. AB - The value of the mass balance strategy is illustrated in the sequence determination of S. aureus V8 protease. Capillary electrophoresis, electrospray mass spectrometry, and high performance tandem mass spectrometry are used as well as proteolysis and Edman degradation. The carboxy terminus is found to contain 17 irregularly repeating units of the triptych motifs NNP and DNP, which provide a challenge to any strategy involving mapping, sequencing, and overlapping of hydrolytic peptides. PMID- 1286940 TI - Structure-toxicity relationships in the amatoxin series. Structural variations of side chain 3 and inhibition of RNA polymerase II. AB - The amatoxins, highly toxic components of death cap Amanita mushrooms, bind strongly to RNA polymerase II (or B) in cell nuclei thus preventing the transcription of DNAs to hn-RNAs (Pre-mRNAs), the precursors of messenger RNAs. Three of the binding sites of the bicyclic octapeptides have been identified: an isoleucine side chain in position 6, a trans-4-hydroxyl group at proline in position 2 and a hydroxylated L-isoleucine side chain in position 3. No information exists about the stereochemical conditions at the beta-C-atom (C-atom 3) of this side chain. We have now synthesized the diastereomeric S-deoxo amaninamides (Fig. 1) containing, in position 3, L-allo-isoleucine (analog 1), (2S, 3R)-2-amino-4-hydroxy-3-methyl butyric acid (analog 2), the diastereomer (2S, 3S)-2-amino-4-hydroxy-3-methylbutyric acid (analog 3) and D-isoleucine (analog 4). In the last synthesis, besides the "normal" bicyclic octapeptide 4, an isomeric Iso-4 was formed. The affinities for Drosophila RNA polymerase II were 100 times weaker as compared to gamma-amanitin for 1, 10 times weaker for 2, 200 times weaker for 3, 100 times weaker for 4, and more than 1000 times weaker for Iso-4. The results point to the importance of a methyl group in (R) configuration at the beta-C atom of side chain 3. PMID- 1286941 TI - Studies on sensitivity to racemization of activated residues in couplings of N benzyloxycarbonyldipeptides. AB - A series of 24 peptides Z-Gly-Xaa(R)-OH where Xaa = 15 different residues and R = H, NH2, tBu, Bzl, Trt, Mtr, and StBu were coupled with valine benzyl ester in dimethylformamide or dichloromethane at +5 degrees. The accompanying racemization was determined by analysis of the epimeric products by normal phase high performance liquid chromatography (HPLC) for Xaa(R) = Met, Cys(StBu) and Lys(Z) and by reversed-phase HPLC after removal of benzyl-based protecting groups for Xaa(R) = Ser(tBu), Thr(tBu) and Arg(Mtr). The coupling methods examined included mixed anhydride (MxAn) at -5 degrees, and N,N'-dicyclohexylcarbodiimide (DCC), benzotriazol-1-yl-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and O benzotriazol-1-yl-N,N,N',N'-tetramethyluroniumhexafluorophosp hate (HBTU) in the presence of 1-hydroxybenzotriazole (HOBt). Very few couplings gave stereochemically pure products. The order of sensitivity to racemization of residues depended on the method of coupling and the solvent. It varied most when comparing MxAn to HOBt-assisted reactions; it varied moderately when comparing HOBt-assisted reactions. There was less variation in comparing BOP and HBTU reactions that are initiated by the same mechanism. Leu, Nle, Phe, Asn, Lys(Z) and Asp(OBzl) are identified as the residues least sensitive to racemization. DCC HOBt generally led to less epimerization than the other methods. PMID- 1286942 TI - Site-specific biotinylation. A novel approach and its application to endothelin-1 analogs and PTH-analog. AB - We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the epsilon-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the epsilon-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle7]ET-1 analog containing epsilon-biotinylaminocaproyllysine at position-9. This peptide, with Kd = 0.08 nM, has 1000-fold higher affinity for the ETA receptor than the commercially available N alpha-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags. PMID- 1286943 TI - Isolation and primary structure of a potent toxin from the venom of the scorpion Centruroides sculpturatus Ewing. AB - A potent toxin has been purified from the venom of the scorpion Centruroides sculpturatus Ewing using the ion-exchange resin CM-Sepharose CL-6B at basic pH. The toxin, designated CsE M1, comprised 65 amino acid residues and its primary structure was established as: Lys-Glu-Gly-Tyr-Leu-Val-Asn-Ser-Tyr-Thr10-Gly-Cys Lys-Tyr-Glu-Cys- Leu-Lys-Leu- Gly20-Asp-Asn-Asp-Tyr-Cys-Leu-Arg-Glu-Cys-Arg30-Gln Gln-Tyr- Gly-Lys-Ser-Gly-Gly - Tyr-Cys40-Tyr-Ala-Phe-Ala-Cys-Trp-Cys-Thr-His Leu50-Tyr-Glu- Gln-Ala-Val-Val-Trp - Pro-Leu-Pro60-Asn-Lys-Thr-Cys-Asn. CsE M1 is the most lethal protein to be identified in C. sculpturatus venom and the LD50 of the toxin, determined by subcutaneous injection into Swiss mice, is 87 micrograms/kg. CsE M1 shows strong structural similarity (92% positional identity) to the most potent beta-toxin, Css II, from the Mexican scorpion, Centruroides suffusus suffusus but is quite dissimilar to the previously characterized toxins with low potency isolated from C. sculpturatus Ewing. PMID- 1286944 TI - [Headache]. PMID- 1286945 TI - [Classical endoscopic diagnostic techniques of the upper and lower digestive tract. Emphasis: esophagogastroduodenoscopy and colonoscopy]. PMID- 1286946 TI - [Endosonography. New insights]. PMID- 1286947 TI - [Classical endoscopic diagnostic techniques of the pancreatobiliary system. Emphasis: ERCP]. PMID- 1286948 TI - [Sonography in gastroenterology. Established and new procedures]. PMID- 1286949 TI - [Abdominal pain, papular exanthema, memory disorders and polyneuropathy in a 50 year-old patient with diabetes mellitus]. PMID- 1286950 TI - [Preview of "Internal Medicine Congress 1993". Preview of workshops of the 99th Congress of the German Society of Internal Medicine in Wiesbaden, 18-21 April 1993, Rhine-Main-Hallen]. PMID- 1286951 TI - [Is there currently an indication for pacemaker implantation in a hypersensitive carotid sinus with asymptomatic, asystolic pauses of 3 seconds in anamnesis, but with syncopes (with no other indications of, for example, rhythmogenic or cerebral origin)?]. PMID- 1286952 TI - [Differential diagnosis of hypereosinophilia syndrome. Comments on the contribution by R. Niehues et al. 67-year-old patient with heart failure and blood eosinophilia]. PMID- 1286953 TI - [Comments on the contribution by R. Niehues et al]. PMID- 1286954 TI - Leishmania major: bacterial contamination of cutaneous lesions in experimental animals. AB - No bacterial contamination has been demonstrated in cutaneous leishmaniasis (CL) nodule and in lesions caused by Leishmania major in Balb/c mice up to 20 days after infection. However, although many phagocytic cells (polymorphonuclear leukocytes and macrophages) were present in the CL lesion, 80% of the lesions showed bacterial contamination that developed within the first 70 days of infection. Topical treatment of the lesion with an ointment containing 15% paromomycin and 12% methylbenzethonium chloride in soft white paraffin for 20 days eliminated all the Leishmania parasites and several of the associated bacteria including: Proteus vulgaris, Pasteurella multocida, Staphylococcus albus and Staphylococcus aureus. This treatment did not affect Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. Total elimination of these bacteria was achieved only during the healing process, and within 20 days following termination of treatment. The rate of disappearance of bacteria inoculated alone into the base of the tail of normal uninfected Balb/c mice was much faster than that of bacteria inoculated into either the CL nodule or the CL lesion. This study suggests the development of local immunosuppression in the CL lesion that may be mediated by the Leishmania parasites and their metabolites. PMID- 1286955 TI - Doppler measurement of left ventricular isovolumic intervals: a study of feasibility and correlation with conventional techniques. AB - Pulsed Doppler echocardiography allows simultaneous recording of left ventricular inflow and outflow blood velocities obtained from the apical 5-chamber view. In this study the feasibility and accuracy of pulsed Doppler measurements of left ventricular isovolumic relaxation and contraction times were compared with those derived from two conventional techniques that combined phonocardiograms and M mode echograms (phono-echo) and M-mode echograms and electrocardiograms (ECG echo). Thirty-seven subjects--24 healthy volunteers and 13 cardiac patients--were examined. Isovolumic relaxation was consistently longer than isovolumic contraction time. Younger age was associated with shorter isovolumic intervals, while heart rate had a negative correlation with these parameters (r = -0.5). Pulsed Doppler measurements of isovolumic relaxation correlated well with phono echo, r = 0.89, and ECG-echo, r = 0.75. Isovolumic contraction times measured by Doppler correlated better with those derived by phono-echo, r = 0.75, than those by ECG-echo, r = 0.4. Better correlations were found for both measurements in the normal subgroup than in the whole group. Difficulty was encountered in measuring isovolumic contraction time by Doppler and ECG-echo in the absence of presystolic A-wave, and in subjects with varying cardiac cycle lengths. Thus, pulsed Doppler measurements of left ventricular isovolumic relaxation times were feasible and consistent with the other methods, while isovolumic contraction intervals by Doppler were not. PMID- 1286956 TI - Colorectal cancer in patients over 70 years old. A prospective study of operative results. AB - All patients (284, mean age 70.8 years) admitted with a diagnosis of primary colorectal cancer to our surgical department during the years 1984-87 were evaluated prospectively. We compare 170 (59.9%) patients > 70 years old and 114 (40.1%) patients < or = 70 years. The overall operability rate was 97.3% and the resectability rate 92.8%. The overall operative mortality rate was 2.1%, four patients in the older group and two patients in the younger group (NS). Among patients who underwent emergency surgery, the operative mortality was 6.1% (4 patients). The overall morbidity rate was 26.7% without significant differences between the two age-groups. A separate subset analysis was done to compare the very old patients (age > or = 80) to the old patients (age 70-79). There were no significant differences between these groups in tumor location, presentation and staging, as well as in operability rate and operative morbidity and mortality. The operative mortality in those over the age of 80 was 3.5%. We concluded that age should not be a determinant in consideration of operation for primary colorectal cancer, since operative mortality and morbidity are similar in both the elderly and their younger counterparts. PMID- 1286958 TI - Standardized mortality ratios for Israel, 1983-86. AB - Standardized mortality ratios (SMRs), standardized by age, sex, continent of birth, and religion are presented by cause and region for the period 1983-86. Regional SMRs ranged from 90.6 in Jerusalem to 107.6 in Ramla. These differences may be due to direct and indirect occupational, environmental and socioeconomic effects as well as to possible health service differences. SMRs can be used to indicate regions where further in-depth epidemiological investigations are called for in order to ascertain the reasons for elevated disease specific SMRs. In addition, SMRs could be used as a global measure of all effects in order to adjust any regional budgetary allocation formula, based on capitation. PMID- 1286957 TI - Confusion as the presenting manifestation of vertebral osteomyelitis: a case report. AB - A 44-year-old patient presented with increasing confusion. He was first diagnosed as having intermittent pressure hydrocephalus but a further evaluation showed CSF pleocytosis and hypoglycorrhachia. Five weeks later, his physical examination was unrevealing. Nuclear imaging techniques were conflicting, with negative gallium- and indium-labelled white blood cells scans but a Tc scan pointing towards a vertebral infection. A well-demarcated lesion in the T9 vertebral body, demonstrated by CT scan, confirmed the diagnosis of vertebral osteomyelitis. Although we were unable to recover the causative organism, antibiotic treatment for presumed staphylococcal osteomyelitis resulted in full recovery. This case indicates that vertebral osteomyelitis may cause significant meningeal inflammation even in the absence of epidural or subdural abscess. We recommend that in patients with meningitis without a clear etiology vertebral osteomyelitis should be considered and pursued with CT scannings of the vertebrae, a procedure that can yield positive findings even when other scanning modalities are negative. PMID- 1286959 TI - Emergency admission to hospital: the family physician as gatekeeper. Results of a 4-year prospective community-based study. PMID- 1286960 TI - Hydrochlorothiazide-induced relapsing fever. PMID- 1286961 TI - Sulfonamide-induced bullous hemorrhagic eruption in a patient with low prothrombin time. PMID- 1286962 TI - Bartter's syndrome presenting as pseudomyocardial infarction and pseudogout. PMID- 1286963 TI - Tricuspid valve replacement and pulmonary valvotomy for carcinoid heart disease: report of a case. PMID- 1286964 TI - Chylothorax complicating repair of congenital diaphragmatic hernia. PMID- 1286965 TI - Tuberculous osteomyelitis of the skull in an Ethiopian immigrant child. PMID- 1286966 TI - Penile metastasis of testicular teratocarcinoma diagnosed by fine-needle aspiration. PMID- 1286967 TI - Embryonic vascular drainage of the endolymphatic sac: the "embryonic endolymphatic glomerulus". PMID- 1286968 TI - Colorectal cancer: surgical risk, biomarkers and primary prevention. PMID- 1286969 TI - Innovations in the diagnosis and management of osteomyelitis. PMID- 1286970 TI - Camel bite: risk factors and management. PMID- 1286971 TI - Lead regulations for workers in Israel: do they protect? PMID- 1286972 TI - Investigation of suitability of devascularized upper half of the whole stomach as replacement for the esophagus. AB - One hundred and fifteen patients with esophageal cancer underwent esophageal replacement with the stomach. The patients were divided into group A (52 patients, stomach tube, ante- or retro-sternal route) and group B (54 patients, devascularized upper half of the whole stomach, posterior mediastinal route). The post-operative complications, post operative symptoms and nutritional status were investigated in both groups. Lung complications tended to occur more frequently in group A (28.8% versus 22.2%), showing no significant difference. The incidence of other complications did not show a remarkable difference between either group except for leakage at the site of anastomosis. Major leakage occurred in 11.5% and 5.6%, and minor leakage in 30.8% and 18.5%, respectively. Postprandial fullness, nausea, heart burn and diarrhea were found to be somewhat higher in Group B. Change of oral intake, body weight and other indices of nutritional status were investigated and compared with pre- operative data. The amount of oral intake and levels of serum albumin was higher in group B than in group A between one and 12 months. These results demonstrate the superiority of the devascularized upper half of the whole stomach as an esophageal substitute. PMID- 1286973 TI - Comparative study of cerebral protection during surgery of thoracic aortic aneurysm. AB - During the past 5 years, 30 cases of thoracic aortic aneurysm were treated. Selective cerebral perfusion (SCP) and retrograde cerebral perfusion (RCP) were conducted for cerebral protection during aortic cross clamping. SCP was carried out in 5 cases of dissecting aneurysm (all Stanford type A, including a case of AAE) and 3 cases of arch aneurysm. RCP was conducted in 5 cases of dissecting aneurysm (4 Stanford type A, 1 Stanford type B with retrograde dissection) and 2 cases of aortic arch aneurysm. The mean cerebral perfusion time of SCP exceeded that of RCP (89 +/- 26 min in SCP versus 61 +/- 33 min in RCP p < 0.05). The hospital mortality rate was 38% (SCP) and 29% (RCP). Neurological complications were prolonged unconsciousness (1/8 in SCP, 1/7 in RCP) and transient paralysis (0/8 in SCP, 1/7 in RCP). Although the mechanism for the cerebral protective effect of RCP is unknown, this perfusion method is easy and safe, requiring little time for ascending and/or arch aortic reconstruction. PMID- 1286974 TI - Ovarian sex cord tumor with annular tubules--a case report and review of the literature in Japanese. AB - A case of ovarian sex cord tumor with annular tubules (SCTAT) in a 41-year-old female is reported. The patient's chief complaint was menstrual irregularity, but the serum values of estradiol and testosterone were not elevated. On gross examination, the left ovary measured 8 x 7 x 6 cm in size and its cut surface was yellowish gray or yellow and solid with no cystic area. Histologically, the tumor was composed of simple and complex annular tubules, lined by columnar cells containing abundant lipid droplets. Eosinophilic materials in the center of the annular tubules were continuous with the basement membrane in the periphery, and showed immunoreactivity for type IV collagen. Also, hollow tubules, consisting of columnar cells with a truncated luminal surface and elongated trabeculae, composed of columnar cells with clear cytoplasm, were noted. These structures were reminiscent of Sertoli cell tumor. Based on these histological observations, it appears that SCTAT is a sex cord/stromal tumor made up of cells with differentiation in the direction of Sertoli cells rather than granulosa cells. PMID- 1286975 TI - Laparoscopic cholecystectomy report of 30 cases. AB - Laparoscopic cholecystectomy (LSC) was attempted in 30 patients and was accomplished in 29 during the nine months between March and November 1991. Twenty eight patients had cholelithiasis with or without adenomyosis, and two had adenomyosis of the gall-bladder. Mean operative time was 219 min and postoperative pain was slight. Two complications (6.9%), including necrosis of the common hepatic duct and subcutaneous emphysema, were encountered. Patients with subacute and severe chronic cholecystitis were included in the cases. Thus this technique is recommended for almost all patients who require the removal of the gall-bladder for benign diseases. PMID- 1286976 TI - Functional deficiency of antigen-presenting cells in the synovial fluid of rheumatoid arthritis. AB - In our study of rheumatoid arthritis (RA) patients, we observed a decrease of tetanus toxoid antigen-presenting capacity of synovial fluid (SF) adherent cells to autologous T cells of either SF or peripheral blood. Additionally, we found a higher capacity of adherent synovial cells to stimulate autologous T-lymphocytes. Our results suggest that antigen-presenting cells of the SF of RA patients have defects that may play a role in defective presentation of antigens in joints and may account for other abnormal functions important in the pathogenesis of RA. PMID- 1286977 TI - HLAs and genes in Japanese patients with multiple sclerosis: evidence for increased frequencies of HLA-Cw3, HLA-DR2, and HLA-DQB1*0602. AB - The distribution of HLA-A, B, C, DR and DRB1, DQB1, DPB1 alleles was studied in 60 Japanese patients with clinically definite multiple sclerosis (MS) using serologic and genomic analysis. We found significant associations with HLA-Cw3 (p = 0.002, pc = 0.012, RR = 3.2), DR2 (p = 0.007, RR = 2.6), and DQB1*0602 (p = 0.04, RR = 4.0) in Japanese patients for the first time. The combined presence of Cw3 and DR2 gave a higher risk than each antigen alone. The reported increase in the frequency of DPw4 in Japanese MS patients [12] could not be confirmed by our genomic study. The frequencies of all of the residues in each variable region of the amino acid sequences of DQ beta and DP beta chains were not different between the MS patients and the controls. These results suggest that MS susceptibility may result from polygenic influences and from the presence of environmental factors. PMID- 1286978 TI - Signal transduction by HLA class II molecules in human T cells: induction of LFA 1-dependent and independent adhesion. AB - Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5' dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways. PMID- 1286980 TI - Cytotoxic flow-cytometric crossmatches (flow-tox): a comparison with conventional cytotoxicity crossmatch techniques. AB - Detection and avoidance of donor-reactive antibodies in the sera of potential organ transplant recipients is key to a successful transplant outcome. Techniques of antibody detection that use flow cytometry are more sensitive than those that rely upon a visual determination of cytotoxicity. However, as conventionally performed, flow-cytometric crossmatches do not distinguish between cytotoxic (complement fixing) and noncytotoxic antibodies because both types of antibodies can bind to a cell and be detected by laser-activated fluorochrome photon emission. In 1989 we described two techniques for detecting cytotoxic antibodies using flow-cytometric techniques [1]. In 1990, we expanded the application of these new techniques that we called flow cytotoxicity assays or "Flow-Tox" [2]. Flow-Tox crossmatches demonstrate an increase in both sensitivity and specificity over conventional cytotoxicity crossmatches. PMID- 1286979 TI - Determination of cytotoxic T-lymphocyte precursor frequencies using europium labeling as a nonradioactive alternative to labeling with chromium-51. AB - We report on the use of europium (Eu) as a suitable nonradioactive alternative for target cell labeling in limiting dilution analysis (LDA) assays set up to determine cytotoxic T-lymphocyte precursor (CTLp) frequencies. A nonradioactive alternative to the commonly used chromium-51 (51Cr) release assay seems desirable because working with radioisotopes has some major disadvantages concerning possible health risks, environmental load, costs of facilities necessary for working with radioisotopes, and shelf life. Some groups have successfully applied the Eu release assay based on detection by time-resolved fluorometry, to tests in which NK- or LAK-cell activity or cytotoxic T-lymphocyte reactions were measured. This led to the investigation whether this method could also be applicable to the more specific determination of CTLp frequencies in LDA assays. After optimal labeling conditions had been established, the sensitivity of the Eu release assay was determined by performing several LDA assays in which the target cells were labeled with either Eu or radioactive 51Cr. When CTLp frequencies were compared, it was shown that the Eu release assay is at least as sensitive and specific as the 51Cr release assay. Moreover, although the labeling procedure takes longer, sample processing is much faster: only 1 second per sample. The fact that the Eu release assay is not radioactive enables the assay to be performed at any laboratory and even--because the frequency of CTLps may have implications for organ graft survival and for donor selection in bone marrow transplantation--to do so on a routine basis. PMID- 1286981 TI - The health of children in foster care. PMID- 1286982 TI - A qualified response. PMID- 1286983 TI - Diagnosis and management of the tethered cord syndrome. AB - Tethering of the spinal cord can occur from a thickened filum terminale, scarring due to myelomeningocele repair, lipomas or diastematomyelia. The typical presentation is a lumbar cutaneous defect, enuresis, unexplained back or leg pain, foot deformities, leg length discrepancies or scoliosis. Spinal ultrasound in neonates and MRI in older children offers ready diagnosis. With laser and microneurosurgical techniques, repair of these defects is safe and effective. The authors recommend that any infant having a mid-line lumbar cutaneous abnormality, such as a hemangioma, lipoma, hair patch or dimple, be evaluated to rule out tethering of the spinal cord. PMID- 1286984 TI - The relationship between life expectancy and socioeconomic status in Arkansas: 1970 and 1990. AB - Life Expectancy at Birth is estimated for county populations in Arkansas in 1970, 1980 and 1990. Counties are grouped into quintiles at each time point according to the percent of persons below the poverty level. Comparisons are made between mean life expectancy in the highest and lowest socioeconomic group at each point in time as well as between the same group at 1970 and 1990. It is hypothesized that the high socioeconomic populations will experience an increase in mean life expectancy over the low socioeconomic populations between 1970 and 1990. Statistical analysis supports the hypothesis. These findings conform to those from earlier research in Ohio and may reflect a continuing deterioration in the relative standard of living of lower income groups in the United States subsequent to 1970. PMID- 1286985 TI - Bringing prosthetics into the 21st century. PMID- 1286986 TI - Robert Booth Moore Sr. PMID- 1286987 TI - Radiological case of the month. Galactocele. PMID- 1286988 TI - A fully automated method for mononuclear bone marrow cell concentration. AB - We describe our experience in processing 40 bone marrow aspirates harvested for autotransplantation from patients with several hematological diseases using the CS-3000 blood cell separator. The bone marrow of the first 30 patients was processed by a semiautomated method, and a fully automated procedure was used for the remaining 10 cases. Both procedures were developed in our laboratory and yielded a similar average mononuclear cell recovery of 87.78% and 86.98%, respectively, and similar nucleated cell recovery (27.39% and 27.11%). The cloning efficiency of hematopoietic progenitor cells, measured as the total CFU GM colony recovery in the in vitro cultures, did not differ between processed and recovered mononuclear cells. On the other hand, all the patients with transplants showed complete hematologic recovery, and the time to engraftment was similar to that described for other procedures. The automated procedure resulted in an average red cell removal of 97.81%, similar to the semiautomated procedure (94.19%), though with a narrower range (96.31-98.6% vs. 80.34-98.34%). The time taken to process a similar amount of bone marrow cell suspension was very different for each method: 1 hour for the fully automated vs. 2 1/2 hours for the semiautomated method to process 1,000 ml. Furthermore, the semiautomated procedure required the addition of homologous or irradiated plasma in a laminar air flow chamber, while the automated method is performed in a closed sterile system. We conclude that our procedure using the CS-3000 processor is an efficient method for fully automated large-scale processing of human bone marrow cells. PMID- 1286989 TI - Analysis of venous access for therapeutic plasma exchange in patients with neurological disease. AB - We retrospectively analyzed our 2-year experience with venous access for 363 therapeutic plasma exchanges in 46 patients with neurological disease, including acute Guillain-Barre syndrome (N = 20), myasthenia gravis (N = 17), and chronic inflammatory demyelinating polyneuropathy (N = 9). Twenty-three patients (50%) completed the planned course of therapy using only peripheral venous access, and 28 central venous catheters were placed in the remaining 23 patients. Patients utilizing central venous access did not undergo a greater number of procedures, but they were more likely to have acute Guillain-Barre syndrome (P < 0.02) or to be hospitalized in a medical intensive care unit (P < 0.01). Three types of central catheters were used, and although our experience was predominantly with 1 type, differences were noted. Only 3% of procedures (3 of 96) done with a Quinton Mahurkar catheter were associated with a catheter failure, compared to 27% (4 of 15, P < 0.01) with a Hickman catheter and 67% (2 of 3) with a triple-lumen catheter. Life-threatening complications occurred with 3 of 28 (11%) central catheters. To optimize the success of therapeutic plasma exchange using central access, it is critical that hemapheresis personnel advise each patient's primary physician regarding the type of central venous catheter required. Currently, we recommend use of a Quinton-Mahurkar or other dual-lumen hemodialysis catheter. PMID- 1286990 TI - Succinylated gelatin as partial fluid replacement in chronic therapeutic plasma exchange. PMID- 1286991 TI - Artificial surfaces in apheresis devices: interactions with the complement system. AB - Blood contacts with artificial surfaces will effect different degrees of complement activation. Associated with complement activation will be cellular concentration and functional changes. The type of anticoagulant also will effect complement activation. The noted biomodulating effect of a material in contact with blood suggests that the choice and design of materials and their "biocompatibility" can be made to effect humoral and cellular changes as the therapy may require. PMID- 1286992 TI - Clinical phenomena induced by complement and leukocyte interactions with artificial surfaces. PMID- 1286993 TI - Leukocyte depletion filters should be used with apheresis platelets. PMID- 1286994 TI - Role of autoantibodies and immune complexes in the pathogenesis of systemic lupus erythematosus. PMID- 1286995 TI - Plasmapheresis therapy is ineffective in SLE. Lupus Nephritis Collaborative Study Group. PMID- 1286996 TI - Central venous catheters for apheresis access. PMID- 1286997 TI - Basic principles of the ABO and Rh blood group systems for hemapheresis practitioners. AB - Since 1901, more than 20 distinct blood group systems have been identified and characterized. Yet, the ABO System, the first described, remains the most clinically significant in blood transfusion and organ transplantation medicine. The ABO antigens are the only cellular antigens which consistently produce a potent, naturally occurring antithetical antibody which circulates in the plasma of healthy individuals. ABO antigens are expressed on most blood cells, organs, and tissues and in most body fluids. Expression of the antigens results from the interaction of several separate, but closely related genes: ABO, H, and Secretor (Se). Blood group specificity depends upon the inheritance of the ABO and H genes, and the subsequent expression of these antigens on the red blood cells. The "D" or Rho antigen is the most clinically significant blood group antigen next to the ABO antigens. The D antigen belongs to the Rh System, which consists of a trio of genes that are so closely linked that they are inherited as a package. The antigens are an integral part of the red blood cell membrane. They lend stability to the membrane structure when they are normal, but result in decreased red cell survival when absent. Rh antibodies are immune antibodies requiring a stimulus and can cause significant transfusion and childbearing complications if present. PMID- 1286998 TI - Basic principles of immunology (immune response) for hemapheresis practitioners. AB - Advances in medical knowledge and technology have identified the essential elements involved in the human immune system, their relationships and interactions, and offer more advanced concepts in the design, function, and maintenance of immune response. Immune response begins with the earliest progenitor cell and transfers its legacy of protection through white blood cells and the complement system. A basic understanding of immunology is essential to the hemapheresis practitioner as new treatment regimens requiring hemapheresis interventions develop. PMID- 1286999 TI - Venous homografts in infra-inguinal procedures: an eight years experience. AB - Autogenous saphenous vein is still the first choice graft material for femoro distal bypass whenever it is available, but the choice of an alternative is still a challenging problem. Between 1982 and 1989, 100 femoro-distal reconstructions were performed with saphenous vein segment homografts, harvested during varicose vein stripping, they were selected, prepared and stored at 4 degrees C. In 71 cases the distal anastomosis was below the knee. According to the actuarial life table analysis (Kaplan & Meyer) the cumulative graft patency rate after 6 months, 1, 3, 5 and 7 years was 79%, 63%, 46%, 45% and 42% respectively. Twelve cases of aneurysm formation or stenosis requiring reintervention occurred. The patency rate was not influenced by the site of the distal anastomosis, but the condition of the run-off vessels had a significant influence on the early occlusion rate. Varicose vein segments are a readily available source of graft material. The low cost, easy storage and handling of these grafts justify their use in limb salvage procedures. PMID- 1287001 TI - An algorithm for the surgical management of chronic abdominal aortic occlusion and occluded aortofemoral grafts. AB - An algorithm for the surgical management of chronic abdominal aortic occlusion is presented based upon experience of treating 60 consecutive patients. Of 33 patients with juxtarenal aortic occlusion, 17 underwent aortofemoral bypass (AFB), 10 descending thoracic aortofemoral (DTAF), 5 axillofemoral (AxF) bypass, and 1 ascending thoracic aortofemoral bypass. Of 11 patients with mid or distal aortic occlusion, 8 underwent AFB, 2 DTAF and 1 AxF. Of 16 patients with aortic graft occlusion, 1 underwent AFB, 10 DTAF and 5 AxF. Acceptable risk patients were selected for AFB (26). DTAF (22) was frequently preferred for patients with occluded aortic grafts or other hazardous intraabdominal pathology. AxF (11) was used for patients with severe cardiopulmonary risk, limited life expectancy from malignancy, or when emergency procedures were required for salvage of severely ischemic limbs in debilitated patients with chronic aortic occlusion. In the AFB, DTAF and AxF groups the perioperative mortality was 8%, 5% and 36% respectively, the late mortality was 15%, 36% and 45%, and the 5-year primary cumulative graft patency was 92%, 89% and 15%. PMID- 1287000 TI - Venous allografts for vascular reconstructions. AB - In order to evaluate various protocols for the preservation of venous allografts 162 arterial reconstructions were performed in mongrel dogs bypassing their ligated femoral arteries. The cumulative 6-month patency-rates as determined by weekly palpation and regular angiography were. Group I = Synthetic grafts: (a) Dacron 48%, (b) PTFE 53%. Group II = Fresh venous grafts: (a) autografts 100%, (b) allografts 37%. Group III = Veins preserved in saline at 4 degrees C for 1 month: (a) autografts 44%, (b) allografts 34%. Group IV = Veins preserved in saline at -70 degrees C: (a) autografts 58%, (b) allografts 47%. Group V = Veins preserved in glutaraldehyde solution: (a) autografts 26%, (b) allografts 22%. Group VI = Veins preserved in Hanks-solution with 15% DMSO at -160 degrees C: (a) autografts 77%, (b) allografts 35%. Histological as well as immunological studies suggest that these results are determined by the preservation protocol in Groups III, IV and V and by the presence of rejection in Groups I and VI. As the results with the allografts are not superior to those obtained with synthetic grafts, their use should be confined to those cases where the use of synthetic materials should be avoided at any price. Further experiments with immunosuppression and antigenic matching are indicated to see whether this would improve the results obtained with viable venous allografts. PMID- 1287002 TI - Intralymphatic antibiotic delivery for reducing acute prosthetic graft infection. AB - The lymphatic system has been implicated as a source of synthetic graft contamination when grafts are implanted in the presence of a distal septic focus. In previous studies, radical lymphatic excision and ligation were shown to reduce acute graft sepsis. However significant lymphedema precluded its clinical application. The present study was undertaken to evaluate methods for reducing acute graft sepsis while avoiding lymphatic obstructive complications. Twenty dogs were divided into one control and two experimental cohorts. Femoral interposition grafts were placed in each dog. A hind paw septic focus was introduced and therapy included a control (Group I--no therapy), intravenous antibiotics in Group II and intralymphatic antibiotics in Group III. Graft, blood and tissue cultures from each dog were taken at 48 hours. Lymphatic antibiotic therapy resulted in significantly improved graft culture results when compared to the control (p = 0.0003) and intravenously treated animals (p = 0.007). Blood cultures in the intralymphatically treated group were also significantly better (p = 0.003) than the control group. PMID- 1287004 TI - Management of solitary iliac aneurysms. AB - Eleven patients with isolated iliac artery aneurysms, presenting over a 10 year period, have been reviewed. Ten patients underwent surgery, of whom 3 had ruptured their aneurysms. Four patients had a solitary aneurysm, while the remaining 6 had 14 aneurysms between them. There was no operative mortality but 2 patients died of late vascular complications (after 4 and 12 months), 1 after proximal ligation only of an internal iliac artery aneurysm, and 1 after proximal and distal ligation and bypass of the common/external iliac artery for an aneurysm involving both the common and internal iliac arteries. Five patients had internal iliac artery aneurysms, and in 4 of these distal control was not achieved. Four patients died from unrelated disease (after 2-6 years). Safe control of internal iliac artery aneurysms cannot be achieved without distal internal iliac control. PMID- 1287003 TI - Aorto-femoral bypass and determinants of early success and late favourable outcome. Experience with 1000 consecutive cases. AB - Experience with 1000 cases of aorto-(bi)femoral bypass is presented evaluating factors influencing the overall patency rate and late survival, over a period of 25 years. There were 820 cases with bilateral and 180 with a unilateral bypass. Mortality was 3.3% and death rate 39.4%. Re-do procedures have been excluded. Operative indications were for stage I disease (moderate claudication) (17.6%), stage II (advanced claudication) (53.2%), stage III (rest pain and/or pregangrenous changes) (22.7%) and stage IV (gangrenous tissue loss (6.5%). Myocardial infarction was the predominant cause of late death in 192 cases (48.7%), followed by cancer in 48 (13%), cerebrovascular disease in 43 (11%), chronic lung disease with cor pulmonale in 15 (3.8%) and miscellaneous causes in 52 (13.2%) of patients. The cause of death was unknown in 31 (7.8%) cases. Co existent peripheral arteriopathy (PAD) noted in 377 (37.7%) patients, was found to be a major determinant of late graft patency. Carotid artery disease and renovascular hypertension were corrected surgically, prior to aorto-femoral bypass in the 5.6% and concomitantly in 4.2%. Coronary artery disease in 273 (27.3%) patients and hypertension in 269 (26.9%), had a great influence on late survival as did age and smoking habits. Endarterectomy together with profundaplasty was carried out in 162 (16.2%) instances. It was our policy to extend the graft limb over the profunda femoris and in cases with co-existent superficial femoral artery disease 208 (20.8%). In 630 (63%) instances, the distal anastomosis was performed at the level of common femoral artery. Immediate graft patency was obtained in 99.3% of the cases. Late patency rate for stages I and II at 5, 10 and 15 years was 82%, 76% and 72% respectively. Following secondary operation for graft occlusion, the 15 year patency was increased to 71%. Co-existent superficial femoral disease can be alleviated by appropriate concomitant profundaplasty. Amputation rates were 0.8% for stage II, 1.5% for stage III and 2.4% for stage IV disease. Twenty year life table analysis showed a reduced survival (54%), in comparison with normal population (77%). PMID- 1287005 TI - Infected aortic aneurysms: CT diagnosis. AB - Infected aortic aneurysms are uncommon but important because they can lead to uncontrolled sepsis and/or aortic rupture. Symptoms are frequently minimal during the early stages and a high index of suspicion is essential to make the diagnosis. The surgical literature suggests that survival is markedly improved by a prompt diagnosis and aggressive surgical intervention. Our recent experience with 5 cases who underwent arteriography and/or computed tomography (CT) prior to surgery was reviewed and these diagnostic methods compared. Traditionally, arteriography has been considered indispensable in the evaluation of infected aortic aneurysms but the aneurysm lumen must reach a certain size before it can be detected and, even then, the extraluminal component may be underestimated. CT, with contrast enhancement, was more sensitive in the early stages of the disease and provided a more complete depiction of the anatomic abnormalities. Mural enhancement preceded the increase in the aortic lumen with disruption of aortic wall calcification. An earlier and more accurate diagnosis can be provided by CT than by angiography without the disadvantages of its invasiveness and cost. PMID- 1287006 TI - Permeability changes following ischemia-reperfusion injury in the rabbit hindlimb. AB - Changes in permeability following ischemia-reperfusion injury were assessed in the intact rabbit hindlimb by measuring the transvascular clearance of 125I labeled rabbit serum albumin. Ischemia was induced for periods of 1 or 2 hours by use of a pneumatic tourniquet inflated to 300 mmHg. Following ischemia, the limb was reperfused for 1, 2, or 3 hours. The albumin clearance in the gastrocnemius muscle of control rabbits was 5.1 +/- 0.7 (mean +/- SEM) microliters/hr/g dry weight. Following 1 hour of ischemia and reperfusion, muscle albumin clearance rose to 71.4 +/- 26 microliters/hr/g dry weight which was not significantly different from those animals that underwent 2 hours of ischemia. Muscle albumin clearance continued to be elevated following 2 hours of reperfusion; however, it returned toward control levels after 3 hours of reperfusion. These data suggest there is a transient increase in albumin permeability following ischemia reperfusion injury in skeletal muscle. PMID- 1287007 TI - An experimental study to examine the patency and tissue response of two types of biosynthetic graft used as a replacement for porcine inferior vena cava. AB - This experimental study has been carried out to evaluate biosynthetic grafts as vascular substitutes. Tubular segments of 35 x 8 mm made of (1) tanned ovine collagen and integral polyester mesh, either of the first (Omniflow I) or second generation (Omniflow II), or (2) polytetrafluoroethylene (e-PTFE), have been sutured in the infrarenal inferior vena cava of pigs, and removed 1 hour, 7, 14, 28, 56 and 112 days after implantation. The patency rate of biosynthetic grafts was higher than that of e-PTFE grafts (p < 0.01). There was no significant difference between the patency of the first generation and second generation collagen grafts. These results indicate that biosynthetic prostheses may be suitable vascular substitutes in low flow and low pressure systems. Improvements in the collagen inner cover structure (Omniflow II vs. Omniflow I), producing greater mechanical endurance, did not enhance long-term patency or the healing patterns of biosynthetic grafts. PMID- 1287008 TI - Pre- vs postoperative pharmacologic inhibition of platelets: effect on intimal hyperplasia in canine autogenous vein grafts. AB - Several clinical studies have shown that pharmacologic inhibition of platelets can increase the patency of vascular grafts, but only if platelet-inhibition is initiated before surgery. This study was performed to compare the efficacy of pre vs postoperative platelet-inhibition on the development of intimal hyperplasia in canine autogenous vein grafts. Reversed femoral veins were used to bypass the ligated femoral arteries in 15 dogs. End-to-side anastomoses were constructed. Eleven dogs were treated with aspirin (325 mg QD) and dipyridamole (25 mg BID). In six dogs treatment was begun 48 hours preoperatively and continued for 3 months. In five other dogs treatment was begun 48 hours after surgery and was continued for 3 months. In 4 control dogs no antiplatelet treatment was given. Excision of the vein grafts 3 months after surgery disclosed reduced intimal hyperplasia (p < 0.05) in the grafts excised from all of the treated animals as compared with those obtained from the control animals. However, there was no difference in intimal hyperplasia observed in the dogs treated both pre- and postoperatively (11 grafts) as compared with those treated only postoperatively (9 grafts). These data demonstrate that it is not necessary to begin antiplatelet therapy preoperatively in order to inhibit intimal hyperplasia. They also suggest that preoperative antiplatelet therapy may improve early graft patency by directly preventing thrombosis, not by inhibiting the development of intimal hyperplasia. PMID- 1287009 TI - Importance of valvular incompetence after acute deep venous thrombosis. AB - The color Doppler scanner was used to analyze acute deep venous thrombosis in 14 patients. A thrombus was found in the superficial femoral vein in 4 patients and in the superficial femoral and popliteal veins in 6 patients; a popliteal occlusion was found in 4 patients. All 14 patients were treated with intravenous heparin followed by at least 3 months of warfarin therapy. Patients were re examined between 24 and 48 months. Six patients were symptomatic; 8 were asymptomatic. Five patients had occluding thrombus in the distal popliteal vein; major competent collateral channels developed from the proximal superficial femoral vein, and they remained asymptomatic. Three patients whose superficial femoral veins recanalized without valvular incompetence were asymptomatic. Valvular incompetence was observed in all of the symptomatic patients. Patients with persistent popliteal occlusion and collateral channels have fewer symptoms than patients with valvular incompetence in the superficial femoral and popliteal veins. PMID- 1287010 TI - Comparison of heated-probe laser Doppler and transcutaneous oxygen measurements for predicting outcome of ischemic wounds. AB - Transcutaneous oxygen (TcPO2) measurement has proven to be an accurate means of predicting healing of ischemic wounds. This study compares the ability of TcPO2 and laser Doppler, modified by the addition of a heated probe (LDHP), to assess wound outcome. TcPO2 and LDHP measurements were made at the same site for 80 wounds, which consisted of 51 amputations (25 above knee, 6 below knee, 20 forefoot) and 29 ulcerations. Healing was defined as complete wound closure. Failure to heal was defined by the necessity for proximal amputation in 22 wounds (6 amputations, 16 ulcers). Outcome criteria were chosen to maximize accuracy and either positive or negative predictive values. Criteria with the greatest accuracy and positive predictive value for wound healing were > or = 11 mmHg for TcPO2 and > or = 50 mv for LDHP range. Criteria with the most appropriate accuracy and negative predictive value for wound failure were < 5 mmHg for TcPO2 and < 35 mv LDHP range. All wounds whose LDHP range was < 35 mv failed to heal, whereas some wounds with a TcPO2 of 0-1 mmHg healed successfully. An absolute prediction of wound healing (100% specificity and negative predictive value) was offered when either LDHP range was > or = 125 mv or TcPO2 was > or = 33 mmHg, although accuracy of either measurement at this criteria was unacceptable for more general application. We conclude that TcPO2 or LDHP will assess wound outcome with similar overall accuracy, although each test may be better for predicting a specific outcome. PMID- 1287012 TI - Profunda femoral artery pseudoaneurysm after percutaneous transluminal procedures manifested by neuropathy. AB - The incidence of arterial complications following femoral artery cannulation is low; however, with the increasing number of cardiac diagnostic and interventional procedures, vascular surgeons are being confronted with an increasing number of pseudoaneurysms and arteriovenous fistulas. Swelling and a painful pulsating groin masse are the most frequent presenting symptoms of a common femoral artery false aneurysm. We present the cases of 4 patients who had the unusual finding of a profunda femoral artery pseudoaneurysm after they had undergone cardiac catheterization or percutaneous transluminal coronary angioplasty. The only clinical sign of these patients was femoral neuropathy or neuropalsy caused by femoral nerve compression. Surgical repair of the pseudoaneurysm was successful in all patients. We discuss the reasons for this unusual finding and rare location for a pseudoaneurysm. PMID- 1287011 TI - Long-term results of the surgical management of symptomatic chronic intestinal ischemia. AB - We analyzed our surgical experience in 20 patients who underwent revascularization procedures for symptomatic chronic intestinal ischemia caused by atherosclerosis. The group comprised 17 women and 3 men, with an age range of 25 to 71 years (mean 58.6 years). Sixteen patients had postprandial abdominal pain, and 4 had pain not related to eating. The average weight loss was 23.8 lb. Malabsorption and diarrhea were present in 8 patients. The duration of the symptoms was from 4 to 46 months (mean 13.4 months). One patient presented with acute intestinal ischemia following balloon angioplasty reocclusion of a stenotic celiac artery, and 3 underwent surgery for stenosis of a previously placed graft. Five patients had single mesenteric artery involvement, 10 had double-artery involvement, and 5 had significant occlusion in all 3 mesenteric arteries. The major arteries were revascularized whenever technically possible; therefore, 36 arteries were revascularized in 20 patients. Bypass grafts were done in 27 vessels, reimplantation in 7, and endarterectomy with patch angioplasty in 2. The saphenous vein was used in 12 vessels, polytetrafluoroethylene grafts in 8, dacron in 6, and inferior mesenteric vein in 1. The type of revascularization or graft utilized did not affect long-term patency. Two patients had early graft thrombosis and required intestinal resection. All patients survived the operation. At a mean follow-up of 36 months, all 20 patients were alive and asymptomatic with regard to their abdominal complaint. Ten patients (50%) underwent postoperative abdominal angiography; all the grafts were patent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287013 TI - Salmonella infection of a Dacron aortic bifurcation graft. AB - We report a case of primary salmonella infection of a dacron aortofemoral bypass graft. Local graft excision with extra-anatomic bypass resulted in a successful outcome. Salmonella, whilst the commonest cause of infected abdominal aortic aneurysms, is currently a rare cause of prosthetic graft infection. However, given the increasing prevalence of salmonellosis in the community, we believe this situation will change and surgeons should be alert to this new and dangerous addition to the list of graft pathogens. PMID- 1287014 TI - A technique for safe resection of extensive tumours associated with the extracranial internal carotid artery. AB - Resection of tumours associated with the extracranial internal carotid artery such as carotid body tumours and paraganglionomas carry a hazard of stroke which might occur from temporary clamping of the artery to obtain better control, or from inadvertent damage to the artery which requires ligation. Some extensive tumours have been deemed unresectable because of their extent. Intracranial extension is a further technical challenge. We describe a technique for safe resection of such tumours employing an outlying Pruitt Inihara shunt. During resection of the tumour the shunt allows safe dissection because the internal carotid artery is rendered relatively bloodless. Further, any damage to the artery can be safely repaired, and indeed if necessary the artery itself can be resected and grafted. We have employed this technique in 3 difficult case of paraganglionoma (1) and carotid body tumour (2) whilst at the same time resecting 8 other simple cases without the need for such a technique. PMID- 1287015 TI - Pretreatment with H2 blocker famotidine to ameliorate protamine-induced hypotension in open-heart surgery. AB - An antagonist to H1 histamine receptor and one to H2 histamine receptor were used to prevent protamine-induced hypotension in 126 Japanese patients undergoing open heart surgery. In a study comparing an H1 antagonist "diphenhydramine" and an H2 antagonist "famotidine", 103 patients were divided into four groups: 31 patients were given no drugs (Group 1), 25 patients were given 0.4 mg/kg of diphenhydramine (Group 2), 33 patients were given 0.4 mg/kg of famotidine (Group 3), and 14 patients were given both the drugs (Group 4) before protamine administration. Although the systolic arterial pressure decreased significantly after protamine administration in all groups, famotidine was found to be effective in reducing protamine-induced hypotension, whereas diphenhydramine was not effective. In order to further investigate the hemodynamic changes in a double-blinded fashion, 12 patients were given normal saline (Group 5), while 11 patients were given 0.4 mg/kg of famotidine (Group 6) before protamine administration. Again, the minimal systolic and mean arterial pressures after protamine injection were significantly higher in Group 6 than in Group 5, while left atrial pressure, central venous pressure, heart rate, and cardiac index were almost the same and remained constant in the two groups. These results strongly suggest that the H2 antagonist "famotidine" is beneficial in reducing protamine induced hypotension after cardiopulmonary bypass, while the H1 antagonist "diphenhydramine" is not. PMID- 1287016 TI - Reduced incidence and severity of accelerated graft atherosclerosis in cardiac transplant recipients treated with prophylactic antilymphocyte globulin. AB - Allograft coronary artery disease (ACAD) is the major factor limiting long-term survival of cardiac transplant recipients (CTRs). Although cyclosporine based triple drug immunosuppression has not decreased the occurrence of ACAD, some preliminary data suggests that prophylactic antilymphocyte preparations may reduce the incidence of this problem. All CTRs at Henry Ford Hospital have uniformly received prophylactic Minnesota Antilymphocyte Globulin (ALG), thereby providing a unique opportunity to investigate this hypothesis. One hundred three CTRs were followed for a median duration of 34 months with annual angiograms begun one year after transplant. Patients who died without an angiogram were considered to have ACAD based on autopsy results or if their death was clinically suspicious. Ninety-two patients underwent at least one angiogram. Fourteen patients had abnormal angiograms. Nine patients were identified as having ACAD by non-angiographic criteria. Five had autopsy proven disease, 3 died suspiciously, and 1 underwent successful re-transplantation for ACAD. By Kaplan-Meier analysis, the risk of developing ACAD was 12% in 1 year, 16% in 2 years, 22% in 3 years, 26% in 4 years, and 29% in 5 years. Risk of ACAD increased with older recipient's age, higher triglyceride levels, and diabetes, but was not affected by active CMV infection, number of acute rejection episodes, and HLA mismatching. These results suggest that prophylactic ALG reduces the occurrence of ACAD. PMID- 1287017 TI - The factors effecting complement activation in open heart surgery. AB - The activation of the complement system was investigated in 10 patients with rheumatic valve disease having heart surgery. The C3c, C4, leukocyte count and polymorphonuclear neutrophil count were determined in the blood samples taken before anaesthesia, after anaesthesia, 10 minutes after protamine administration and after the closure of the skin incision. In addition, atrial blood samples were taken after the release of the cross-clamp and pulmonary neutrophil trapping was investigated. In this study C3c and C4 consumption was found to take place after 30 minutes of CPB (cardiopulmonary bypass) and 10 minutes after protamine administration; the affects of anaesthesia and heparin were not significant. PMID- 1287018 TI - Somatomedin-C plasma levels after coronary revascularization. AB - The decrease of Somatomedin-C (SM-C) plasma levels has been recently proposed as an index of acute malnutrition in critically ill patients. In this study SM-C values were determined before surgery for coronary revascularization, on the 2nd and 5th postoperative day. Twenty-four patients were admitted to the study; most of them (16 cases; 66%) presented with an increase of SM-C levels after surgery unlike 8 patients who showed unchanged or decreased levels. Multivariated analysis was applied to the factors that may affect SM-C values. SM-C significantly related to the Modified Predictive Nutritional Index, which was calculated prior to surgery, while no significant relationship was observed with patient age and type of oxygenator. No sign of liver damage was observed, so we concluded that decreased and, perhaps, unchanged SM-C levels after coronary revascularization were probably caused by acute nutritional deficiency. The incidence of this finding was remarkably high (33%) in spite of the absence of apparent malnutrition before surgery. PMID- 1287019 TI - Multiple primary left ventricular myxomas with multiple intraventricular recurrences. AB - A 23-year-old male was operated on for two primary left ventricular myxomas of the "complex" type. Ten months later, abnormal echo reappeared and reoperation was carried out to excise 2 recurrent myxomas in the left ventricle. Multiple foci were most likely responsible for the recurrence. No recurrence has been detected for 20 months postoperatively. This may be the first reported case of multiple primary left ventricular myxoma with multiple recurrences in the left ventricular cavity. PMID- 1287020 TI - Primary cardiac paraganglioma. Case report and review of surgically treated cases. AB - A 58 year old man with an infiltrating non-resectable left atrial paraganglioma was diagnosed by sternotomy and open biopsy. The patient remains symptom free 16 months after the operation. No evidence of an increase in the size of the tumour has been detected by echocardiography. The literature regarding surgically treated patients with cardiac paragangliomas is reviewed. PMID- 1287021 TI - What is medicine? PMID- 1287022 TI - From the Halls of Ivy to the thundering horde. PMID- 1287023 TI - A critical appraisal of chromatographic and immunoassay techniques for clinical drug analysis. AB - Chromatography and immunoassays are the two principal techniques used in research and clinical laboratories for the measurement of drug concentrations in biological fluids. The purpose of this article is to provide the reader with a general overview of these techniques and to present their relative merits and limitations. A glossary of technical terms is included at the end of the review. PMID- 1287024 TI - The importance of side effects and outcomes in differentiating between prescription drug products. AB - This study determined the importance of side effects and outcomes (i.e. the control of disease, convenient dosing and cost) in physicians' differentiation of drug products used to treat hypertension, allergic rhinitis, and gastroesophageal reflux. In addition, the study examined whether the importance of particular characteristics attributed to a drug varied with the practice setting. The multiattribute attitude model was used as a framework to examine physicians' perceptions of the importance and the probability of occurrence of specified side effects, results and their prescription intentions. Two groups of physicians were interviewed to identify determinant side effects and results. A questionnaire was used to obtain data by post from a random sample of 2,400 physicians in four types of practices: solo practice, group practice, institution and government (n = 527, 22% response). The findings indicate that the perceived likelihood of occurrence of side effects and results differed with the drug products but did not differ with the type of practice. Practice setting, however, was found to have a significant effect on intention to prescribe. Physicians in each setting differed in their intentions to prescribe certain studied drugs. Finally, physicians in the four settings were found to be similar in their ranking of the importance of particular characteristics of the drug. The control of disease was the most important result in all three scenarios, followed by individual side effects. PMID- 1287025 TI - Vitamin C aspirin interactions in laboratory animals. AB - Ascorbic acid concentration has been determined in samples of plasma, leucocytes, urine, faeces and adrenal glands of guinea-pigs after administration of (i) 10, 25 or 100 mg ascorbic acid, (ii) 10 mg ascorbic acid plus 10, 25 or 50 mg aspirin and (iii) 25 mg aspirin and 25, 50 or 100 mg ascorbic acid. When the dose of aspirin was 25 mg or more, the transport of ascorbic acid into leucocytes was inhibited, the plasma concentration of vitamin C was elevated significantly and the excretion of ascorbic acid in the urine was increased in direct proportion to the aspirin dose. Ascorbic acid concentration in the adrenal glands was not significantly elevated after 3 h. When a constant dose of 25 mg of aspirin was given along with increasing doses of ascorbic acid both plasma and leucocyte ascorbic acid levels were elevated but not significantly after 2, 3 and 24 h. Urine ascorbic acid levels did not show any changes with the same doses. PMID- 1287026 TI - An analysis of clinical pharmacist interventions in an intensive care unit. AB - In a 6-month study period, 170 pharmacist interventions in an intensive care unit (ICU) were analysed. Of the interventions, 68.8% were solicited and 31.2% were initiated by the pharmacists. The majority of the interventions were initiated by specialists (69.4%) followed by the medical officers (15.9%) and nurses (9.4%). Most of the interventions occurred during the grand rounds (75.9%), followed by ward visits (12.9%) and communication through the satellite pharmacy (10.5%). The most frequent type of intervention made was for indication or therapeutic efficacy followed by general product information, drug regimen, laboratory assessment, disease state, pharmaceutical availability and adverse drug reaction or side effect. It was also found that 83.7% of pharmacists' suggestions were accepted, 6.4% were accepted with changes, and 9.9% were not accepted. The majority of the interventions were made by direct verbal communications followed by telephone and written communications. In conclusion the study indicates that pharmacist therapeutic recommendations form an important integral element of patient care in an ICU. PMID- 1287027 TI - Drug utilization in community pharmacy. AB - Drug utilization studies are a powerful means of identifying problem areas in drug consumption. The defined daily dose/1,000 inhabitants/day (DHD), provides an estimate of the proportion of the population who receive drug treatment in ambulatory care at national, regional, local and institutional levels. A new unit and its formula has been developed; defined daily dose/100 consumers/day (DCD), for the determination of drug utilization from community pharmacy allocated in cities where it is difficult to estimate the population covered by each pharmacy. This formula was applied to a community pharmacy to obtain the utilization of drugs for peptic ulcer treatment in 1990 and 1991. The data are compared with regional DHD data and there is good agreement between the results of the two methods. Data on non-prescription drug utilization are not easily available, and community pharmacists could improve the information available for this groups of drugs through use of the proposed formula and unit. PMID- 1287028 TI - Serum drug level monitoring in affective disorders. AB - This study surveyed serum level monitoring of lithium and carbamazepine in three psychiatric hospitals, to determine how the service is used with respect to affective disorders. The monitoring of lithium serum levels appears to be carried out in relatively close adherence to recommended guidelines. Carbamazepine serum levels are monitored with a similar frequency to lithium, despite the lack of an established therapeutic window for indications other than epilepsy. Changes in drug therapy, which are consequent upon monitoring of serum drug levels, occurred after only 7.5% of lithium and 13.7% of carbamazepine samples. Changes were made independently of serum level results with greater frequency in carbamazepine treated patients, although less frequently with lithium-treated patients. Adverse consequences of such changes occurred only once, involving lithium. More research is needed to determine the potential benefits of carbamazepine serum level monitoring in affective disorders because the service appears to be overutilized at present. PMID- 1287029 TI - Variability in clinical pharmacology of drugs in children. AB - Numerous factors can lead to variability in pharmacokinetics, pharmacodynamics, efficacy, and toxicity of drugs in infants and children. These may include age, race or genetic status, organ function, underlying disease(s), drug formulation, concomitant drugs, and compliance with therapy. Further research is needed to clarify the mechanisms for variability in drug response to achieve optimal use of drugs in paediatric patients. PMID- 1287030 TI - A drug usage review of omeprazole. AB - A drug use review of omeprazole was carried out at two centres in the Yorkshire Region from December 1990 to April 1991. Data collection documents were used and 66 patients in total were audited. Thirteen patients (19.7%) were treated for indications outside the product licence and 18 patients (27.3%) were treated for longer than 8 weeks. Twenty-eight patients (42.4%) received 40 mg daily. Fifty one patients (77.3%) had received previous therapy with H2-receptor antagonists and in 33% of these patients it was at an inadequate dose or for an inadequate period of dosing or both. The results indicate a need for a prescribing policy for omeprazole. PMID- 1287031 TI - Non-pharmacological treatment of hypertension. AB - This paper represents a compilation of the latest scientific research on the non pharmacological management of hypertension to help practitioners manage this highly prevalent disease. In this regard, recent evidence suggests that nonpharmacological approaches--particularly weight reduction, salt restriction, moderation of alcohol consumption, reduction of cholesterol intake and exercise- may lower elevated pressure and improve the efficacy of pharmacological agents. Non-pharmacological therapy should be stressed for the future treatment of hypertension. PMID- 1287032 TI - Targeted kill: from umbrellas to monoclonal antibodies. PMID- 1287033 TI - Lupus anticoagulant antibodies inhibit collagen-induced adhesion and aggregation of human platelets in vitro. AB - The effect of circulating lupus anticoagulant on platelet interaction with collagen and other proteins was tested, with the aim of understanding the role of membrane phospholipids in platelet function. Plasma samples from 26 systemic lupus erythematosus (SLE) patients, containing circulating lupus anticoagulant (LAC), were examined for their effect on adhesion and aggregation of normal human platelets. We find that SLE plasma, but not normal plasma, inhibits platelet adhesion to collagen in a concentration-dependent manner. At a plasma concentration of 1% the inhibition was 73 +/- 9% (mean +/- SD). In sharp contrast, there was no effect on platelet adhesion to fibronectin. Purified IgG from the same plasma samples also had an inhibitory effect. At 15 micrograms/ml (comparable in IgG concentration to 0.1% plasma) it inhibited adhesion to collagen by 33 +/- 11%. Inhibition could be abolished by preincubation of the LAC containing plasma with cardiolipin (CL), phosphatidylinositol (PI), and, to a lesser extent, phosphatidylserine (PS) but not with phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Inhibition could also be abolished by preincubation of the LAC-containing plasma with a 10-fold excess of washed normal platelets. The effect of 1% LAC plasma on platelet aggregation was as striking, showing 79 +/- 26% inhibition of collagen-induced aggregation, and it could also be abolished by preincubation of the LAC plasma with cardiolipin. In contrast, the effect of LAC plasma on thrombin-induced aggregation was rather modest. Our results indicate that antiphospholipid antibodies interfere with platelet adhesion and stimulation by collagen in vitro and point to an important role of external plasma membrane phospholipids, particularly PI, in collagen-induced platelet activation. PMID- 1287034 TI - Immunological studies in the hyper-immunoglobulin D syndrome. AB - Five patients with hyper-immunoglobulin D syndrome (hyper-IgD syndrome) were followed up for 3 to 8 years. In all patients studied, serum IgG3 was high. IgM decreased during the follow-up in all patients. In four of the patients serum IgA was elevated. In four patients the serum IgD kappa/lambda ratio was measured and was found to be raised in all. However, the serum total light-chain ratio and IgG, IgA, and IgM kappa/lambda ratios separately were virtually normal. In two of the patients, clinical symptoms preceded the increase in serum IgD. All patients had a history of severe reactions on immunizations in early childhood. We conclude that in hyper-IgD syndrome, other immunoglobulins may also be affected, in particular, IgA, IgM, and IgG3. The IgD light-chain ratio is also disturbed. We emphasize that clinical symptoms may herald immunological changes. This may be the result of an underlying factor causing both the clinical symptoms and, later, the increasing serum IgD levels. PMID- 1287035 TI - Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160. NIAID AIDS Vaccine Clinical Trials Network. AB - Serum antibody responses were studied in detail in four vaccinia-naive volunteers in a phase I trial evaluating primary vaccination with a recombinant vaccinia virus expressing the HIV-1 gp160 envelope glycoprotein (HIVAC-1e, Oncogen/Bristol Myers Squibb), followed by booster immunization with baculovirus-derived rgp160 (VaxSyn, MicroGeneSys). Prior to boosting, low-titer Fc receptor (FcR)-mediated, antibody-dependent enhancing (ADE) activity was detected in two of four volunteers but no IgM, IgG, IgA, neutralizing activity, or complement-mediated ADE activity was detected. Two weeks after boosting, all four volunteers developed HIV-1-specific IgG with titers of 1:160 to 1:640 by immunofluorescence assay. IgG1 was present in sera from each individual, while IgG2 and IgG3 were present in sera from two individuals, and IgG4 was present in serum from one individual. IgM and IgA were undetectable in all sera. Only one volunteer had IgG to the heterologous HIV-1 isolates, RF, MN, and SF2, after boosting. Serum from this volunteer neutralized the vaccine strain, LAV/IIIB, but not the heterologous strains, RF, MN, and SF2. Antibodies from the remaining volunteers had no neutralizing activity. The neutralizing serum had a positive reaction in a peptide-based ELISA utilizing a peptide corresponding to the principal neutralizing domain of the third hypervariable region (i.e., V3 loop) of the envelope glycoprotein. Neutralizing activity was partially removed by adsorption to this peptide, suggesting that it contained a type-specific neutralizing vaccine epitope. A low titer (1:40 to 1:80) of complement-mediated ADE activity to HIV-1 IIIB was present in sera from three vaccinees after boosting. FcR-ADE activity for HIV-1 SF2 and SF-128A were present in sera from two of these three vaccinees. None of the volunteers developed antisyncytial antibodies. These results indicate that inoculation with recombinant vaccinia followed by rgp160 boosting is the most effective strategy to date for inducing serum antibodies to the envelope glycoproteins of HIV-1, but further study is needed to optimize the functionality and cross-reactivity of these responses. PMID- 1287037 TI - Does public health still include environmental health and protection? PMID- 1287038 TI - The making of public health data: paradigms, politics, and policy. AB - Public health data do not simply exist: the variables included or excluded from any given data set reflect the choices of individuals and institutions with the power to make these decisions. Their judgement typically is guided by prevailing theories of disease causation, which in turn usually resonate with their society's predominant political, economic, and ideological characteristics. This essay examines the making of public health data as a social process, both historically and in the present, and critiques the routine omission of social class data from US public health data bases, the treatment of "race" and "sex" as primarily biological variables, and their conflation with ethnicity and gender. Overcoming these problems will require developing social theories of disease causation and ending the pervasive silence about the health consequences of class, race, and gender inequalities. PMID- 1287036 TI - Effects of in vivo endotoxin infusions on in vitro cellular immune responses in humans. AB - Studies of the immune response of patients following major injury have identified significant abnormalities, some of which may be due to the effects of endotoxin. To evaluate the effect of endotoxin on the immune system without conflicting variables, we studied 18 normal, healthy male volunteers each on two occasions. In one study, Escherichia coli endotoxin was administered intravenously at a dose of 4 ng/kg. In the other, saline was given. Blood for immune function studies was obtained at either 0, 4, or 24 hr (seven volunteers), 0, 1, and 4 hr (five volunteers), or 0, 4, and 6 hr (six volunteers) postinfusion. Peripheral blood mononuclear cells (PBMC) were isolated and adjusted to the same concentration. Measurements following endotoxin infusion were compared with those of the same volunteers following saline infusion and with those from normal ambulatory laboratory volunteers. Interleukin 1 (IL-1) production by adherent cells was significantly reduced at 1 hr post endotoxin infusion. Significant decreases in number of mononuclear cells, response to phytohemagglutinin (PHA), and production of IL-2 and IL-1 were observed by 4 hr after endotoxin infusion. No significant changes in percentages of monocytes, lymphocytes, or CD3, CD4, or CD8 lymphocytes were observed at any time. By 24 hr postinfusion all values had returned to normal or, in some cases, supranormal levels. Response to PHA by PBMC from volunteers 4 hr following endotoxin was completely restored by in vitro addition of recombinant human IL-2 but was only marginally improved by IL-1. In vitro addition of indomethacin to PBMC cultures responding to PHA reduced the suppression observed after in vivo endotoxin but also was not as effective as IL 2. In a fourth study, seven volunteers were treated as above either with two doses (800 mg each) of the cyclooxygenase inhibitor ibuprofen before endotoxin infusion or with ibuprofen alone. Ibuprofen pretreatment completely restored the PBMC response to PHA to normal and caused a significant decrease in the endotoxin induced suppression of IL-2 production. However, the decrease in circulating PBMC number and adherent cell secretion of IL-1 was not affected by inhibition of the cyclooxygenase pathway. These results suggest that endotoxin has immunomodulatory effects on both adherent mononuclear-cell and T-lymphocyte function and that more than one mechanism is involved. PMID- 1287039 TI - Teaching health policy and politics in U.S. schools of public health. AB - Because most public health endeavors in the United States are funded by the public sector, public health practitioners need to be adept at working within the political system. However, the 1988 Institute of Medicine report, The Future of Public Health, found that many public health professionals are ignorant or disdainful of political processes and will not participate in activities that they perceive to be political. Our study examined the health policy and politics curricula of the 24 accredited schools of public health in the U.S., finding that most public health students are not exposed to these areas during their graduate coursework. Moreover, those students who do take health policy and politics courses study these areas within the context of health care delivery; the politics of public health and prevention are ignored by most schools of public health. Recommendations for improving public health curricula in health policy and politics are presented, including linkages with prevention activities. PMID- 1287040 TI - Estimating costs of traffic crashes and crime: tools for informed decision making. AB - Traffic crashes and crime both impose significant economic and social burdens through injury and loss of life, as well as property damage and loss. Efforts to reduce crashes and crime often result in competing demands on limited public resources. Comparable and up-to-date cost data on crashes and crime contribute to informed decisions about allocation of these resources in important ways. As a first step, cost data provide information about the magnitude of the problems of crashes and crime by allowing us to estimate associated dollar losses to society. More importantly, cost data on crashes and crime are essential to evaluating costs and benefits of various policy alternatives that compete for resources. This paper presents the first comparable comprehensive cost estimates for crashes and crime and applies them to crash and crime incidence data for Michigan to generate dollar losses for the state. An example illustrates how cost estimates can be used to evaluate costs and benefits of crash-reduction and crime-reduction policies in making resource allocation decisions. Traffic crash and selected index crime incidence data from the calendar year 1988 were obtained from the Michigan State Police. Costs for crashes and index crimes were generated and applied to incidence data to estimate dollar losses from crashes and index crimes for the state of Michigan. In 1988, index crimes in Michigan resulted in $0.8 billion in monetary costs and $2.4 billion in total monetary and nonmonetary quality-of-life costs (using the willingness-to-pay approach). Traffic crashes in Michigan resulted in $2.3 billion in monetary costs and $7.1 billion in total monetary and nonmonetary quality-of-life costs, nearly three times the costs of index crimes. Based on dollar losses to the state, the magnitude of the problem of traffic crashes clearly exceeded that of index crimes in Michigan in 1988. From a policy perspective, summing the total dollar losses from crashes or crime is of less importance than understanding the costs and benefits of various policy alternatives. This paper therefore concludes with an example of how our cost estimates can be used to compare the costs and benefits of competing policies. PMID- 1287042 TI - Back to direct payment: German dentists lobby to leave the national sickness fund scheme. AB - Oral health care in Germany is delivered by private dentists working predominantly in solo practice. Services are financed indirectly by sickness funds for 89 percent of the population. With caries rates declining, dentists' numbers increasing, and federal policies changing the remuneration regulations to enhance preventive behavior in consumers, dentists are concerned about their shrinking incomes. In an attempt to secure their professional interests, a faction among dentists advocates to return to direct payment and to opt out of the sick fund scheme. Their strategy and professional goals are described and the chances of succeeding discussed. PMID- 1287041 TI - Changes in Medicare billing patterns: implications for physician payment reform. AB - This paper examines the changes in the billing for office visits, hospital visits, and consultations in the Medicare program for the period of 1986 through 1988. The analysis does not correct for changes in beneficiary or provider characteristics over the three-year period. Findings indicate $75 million in additional Medicare expenditures due to change in pattern of physician charges for these three commonly performed groups of procedures. PMID- 1287043 TI - China's Cooperative Medical System: its historical transformations and the trend of development. AB - The rural Cooperative Medical System (CMS) in China came into existence in the 1950s. Along with the development of the collective economy of agriculture and the promotion of this system by the Chinese Government, the coverage rate of the CMS in the rural areas increased from 1955 through the end of the 1970s, when it was estimated that 90 percent of the rural population was covered by the CMS. Since the rural economic reform in the early 1980s destroyed the rural collective economy on which the CMS was based, The coverage rate of the CMS went down to 5 percent. After 1985, the coverage rate of the CMS began to increase gradually because of the development of the collective fund for supporting the CMS and the governments' efforts to strengthen the CMS. The structure of CMS has changed over time. Traditionally, the CMS was organized at the village level. In order to increase the risk-sharing ability of this system, the trend is for it to be organized at the township level in the future. PMID- 1287044 TI - Spontaneous recovery of vision in progressive anterior ischemic optic neuropathy. AB - Four patients with typical anterior ischemic optic neuropathy experienced progressive deterioration of visual function, to acuity levels of finger-counting in two eyes, 20/400 in one, and 20/50 in the fourth. All subsequently enjoyed significant spontaneous recovery of vision to 20/60, 20/60, 20/40, and 20/25, respectively. No previous reports have documented the details of such improvement in the progressive form of anterior ischemic optic neuropathy. The natural history of this common optic nerve disorder is reconsidered in light of these observations. The potential for spontaneous recovery should be taken into account in the interpretation of visual outcome in medical or surgical therapeutic trials for progressive anterior ischemic optic neuropathy. PMID- 1287045 TI - Papillophlebitis and arteriolar occlusion in a pregnant woman. AB - Among the pathologic findings affecting the eye during pregnancy, microvascular abnormalities affecting both choroidal and retinal circulation have been reported in cases of complicated pregnancy. We report a case of papillophlebitis and arteriolar occlusion in a pregnant woman without any complications throughout her pregnancy. The patient was placed on glucocorticoids and her vision, visual fields and funduscopic appearance improved almost to normal. Despite the improvement with treatment, the contributing role of glucocorticoids in this case could not be fully determined. Papillophlebitis and arteriolar occlusion should be included among gestational-related vasculopathies. PMID- 1287046 TI - Compression of the intracranial optic nerve mimicking unilateral normal-pressure glaucoma. AB - A 66-year-old man developed progressive visual field loss in the inferior arcuate region of the right eye with normal central visual acuity. Intraocular pressures were normal on all but one occasion. The right optic disk showed extensive glaucomalike cupping; the left optic disk was normal. Magnetic resonance imaging revealed a tumor of the right medial sphenoid wing impinging upon the intracranial portion of the right optic nerve. It was resected via a frontotemporal craniotomy. Histopathologic examination revealed a meningothelial meningioma. The visual field and optic disk cupping remained unchanged postoperatively. To our knowledge, this is the first report in which both glaucomalike cupping and visual field loss occurred as the result of a compressive lesion of the anterior visual pathway. PMID- 1287047 TI - Asymptomatic unilateral papilledema in pseudotumor cerebri. AB - A 32-year-old asymptomatic woman was found to have unilateral papilledema on routine ophthalmological examination. Subsequent visual field, neuroimaging, and cerebrospinal fluid examinations were consistent with the diagnosis of pseudotumor cerebri. This case demonstrates that pseudotumor cerebri may present as unilateral papilledema in any asymptomatic patient and illustrates the need for thorough neuro-ophthalmological evaluations to allow early detection of cases with atypical presentations to increase the efficacy of therapeutic intervention and prevent progressive visual loss. PMID- 1287048 TI - Visual hallucinations on eye closure after cardiovascular surgery. AB - Visual hallucinations on eye closure are very uncommon. The underlying mechanism remains controversial. We report on a new case after carotid endarterectomy and coronary artery bypass graft surgery. The hypothesis of a temporal lobe epilepsy is discussed. PMID- 1287050 TI - Bipolaris-induced orbital cellulitis. AB - We report a patient who rapidly developed unilateral proptosis and complete ophthalmoplegia following blunt trauma to the orbit. Computed tomography (CT) scan revealed a mass involving the sinuses and orbit with erosion of the cribriform plate. Biopsy of this suspected neoplasm revealed features consistent with allergic Aspergillus sinusitis, but cultures later grew a Bipolaris species. Our review of the literature suggests that when allergic fungal sinusitis involves the orbit, Bipolaris is a more commonly isolated organism than Aspergillus. Additionally, extraocular motility impairment and proptosis occur more frequently than visual loss. Treatment is controversial, but surgical drainage followed by corticosteroids is the most often recommended therapy. PMID- 1287049 TI - Indolent orbital apex syndrome caused by occult mucormycosis. AB - The chronic or indolent presentation of rhino-orbital mucormycosis, as defined by the presence of symptoms for more than 1 month before diagnosis, is extremely unusual. A 45-year-old man with stable diabetes presented with a right orbital apex syndrome and minimal ethmoid and sphenoid sinusitis. Progression was indolent, and the diagnosis was not made until 7 weeks after admission, when a third biopsy was prompted by new cavernous sinus and carotid artery thromboses. Mucormycosis was found. The patient improved on amphotericin B (2 g) and strict blood glucose control. A remarkable aberrant regeneration of the right oculomotor nerve was seen following treatment. He remains free of active disease 4 years later. Orbital symptoms in well-controlled diabetics, which may even remain stable for weeks and lack direct signs of tissue invasion, should raise the suspicion of mucormycosis. PMID- 1287051 TI - The unidirectionality of cerebral polyopia. AB - Polyopia, visual perseveration in space, has been associated with seizure activity, afterimage formation, and the presence of visual field defects. It can be interpreted both as a positive and a negative visual phenomenon. A patient with polyopia associated with the acute onset of hemianopsia is presented. The phenomenon has been investigated objectively with a simple procedure. The polyopia was highly correlated to movement of the eyes into the hemianoptic visual field and to increased contrast but not duration of the stimulus. This type of polyopia could be the result of incomplete visual processing due to poor visuospatial localization in a hemianopic field. PMID- 1287052 TI - Isolated bilateral abducens nerve palsies caused by the rupture of a vertebral artery aneurysm. AB - We report two cases with isolated bilateral abducens nerve palsies due to the rupture of a vertebral aneurysm. Surgery revealed that the aneurysm did not directly compress the abducens nerve. Within a year after the subarachnoid hemorrhage, the patients gained full recovery from the bilateral abducens nerve palsies. In view of the clinical and operative findings, it may be regarded as a compression and/or stretching of the bilateral abducens nerves by a thick clot in the prepontine cistern, and not as a manifestation of the raised intracranial pressure. The mechanisms of the isolated abducens nerve palsy are discussed. PMID- 1287053 TI - Ophthalmoplegia as a presenting manifestation of internal carotid artery dissection. AB - We present the case of a patient with an ipsilateral ophthalmoplegia as the presentation of a traumatic dissection of the internal carotid artery. We hypothesize that the cranial nerves dysfunction occurred because of interruption of the vascular supply to the nerves in the cavernous sinus from the inferolateral trunk of the cavernous carotid artery. PMID- 1287054 TI - Renal causes of elevated sedimentation rate in suspected temporal arteritis. AB - The erythrocyte sedimentation rate (ESR) is a frequently used but nonspecific indicator of inflammation or infection. Clinicians often check an ESR in patients with symptoms of headache, facial or jaw pain, and visual loss, as an aid in the diagnosis of temporal arteritis. We present two patients with these complaints, who did not have temporal arteritis, nor any other inflammatory condition or infection, but had ESRs near or above 100 mm/h, leading to diagnostic confusion. An occult nephrotic syndrome, with or without renal insufficiency, can cause such a highly elevated ESR, and was discovered in these patients. PMID- 1287055 TI - History of neuro-ophthalmology grand rounds at the Washington Hospital Center. PMID- 1287056 TI - Cases from the Washington National Eye Center monthly neuro-ophthalmology conferences. PMID- 1287057 TI - What is the proper integration of optometry and ophthalmology? AB - The delivery of health care services in America today utilizes a variety of approaches based on many economic, political and social factors. The current health care system is coming under significant review and criticism. Many options are being considered and recommended. This paper addresses possible changes in the delivery of eye care, specifically the relationship between the professions of optometry and ophthalmology, that may be needed in the future. PMID- 1287059 TI - How can the optometric profession expand the pool of qualified applicants? AB - Recruitment endeavors are underway to increase the "dwindling applicant pool" of optometric professionals. Referrals, scholarships and including pre-optometry courses in undergraduate curriculums are some of the recommendations. PMID- 1287058 TI - What are the pros and cons of requiring postgraduate residency training as an entry-level practice requirement? AB - Postgraduate residency training would produce better trained optometrists to meet the future needs of optometry. While residency training would expose a new graduate to experience that may take years to acquire, currently there is no mechanism in place to accommodate such a program. PMID- 1287060 TI - Are graduate programs in physiological optics fulfilling their original purpose? AB - Change has affected physiological optics graduate programs' fulfillment of their original purpose of providing faculty for the schools and colleges of optometry. Relevant change has been divided into two categories: 1) change in optometry and optometric education, and 2) change in the characteristics of students opting for graduate study. The answer to the question posed is that these programs are still preparing faculty for academic careers, but not in the numbers they once did. A few consequences and options are considered. PMID- 1287061 TI - Characteristics of faculty for a successful basic sciences program. AB - The author defines characteristics of an ideal faculty for a successful basic science program including strong grounding in the specific discipline, ability to teach with clinical relevance, dedication to teaching above all other considerations, and motivation to integrate optometric science. He illustrates an approach to this ideal as developed at the Southeastern University of the Health Sciences by integrating the basic science faculty for three separate health profession schools. Further, the author describes the profitable examples which have come about through this program. PMID- 1287062 TI - Basic science research in optometry: are we adequately prepared? AB - Optometry has not traditionally emphasized basic science research. With the increasing responsibilities taken on for the health care of our patients, it is essential that optometry develop its own scientific base of knowledge on which to rely. The need for good scientific investigators, the need for support for basic science research, as well as the importance of long-range planning for basic science research in optometry are discussed. PMID- 1287063 TI - Changes are needed to ensure the future of optometry's graduate programs: a critical issue. AB - Optometry is at a crossroad. As it changes focus and alters course, it must be supported academically by viable research and graduate programs. This requirement is current and pressing. This paper addresses several issues involved in this critical endeavor. Needs and opportunities are discussed. PMID- 1287064 TI - Ensuring the future of optometry's graduate programs. AB - Financial burdens, time and family commitments, peer status, insecure feelings concerning academia, and continuing "student" stigma are some of the pressures that discourage optometrists from entering graduate programs in visual science or other fields. In order to ensure the continued future training of optometrists with additional graduate degrees, we must begin to develop better financial packages, proactive recruitment strategies, increased networking opportunities, more secure career opportunities, streamlined graduate programs, and the affirming of the rewards of graduate study by those who have had successful careers. PMID- 1287065 TI - Implication of the expanding scope of practice on the financial needs at the schools and colleges of optometry. PMID- 1287066 TI - An analysis of external sources for revenue solicitation for optometric education. AB - In analyzing the costs of optometric education, it becomes apparent that the cost of operating the educational institution far exceeds the cost of providing the optometric education. A recent survey also indicates that there are rather striking differences in the cost of operating state-sponsored vs. private programs. It is necessary, therefore, to seek alternative sources of funding optometric education rather than relying on annual tuition escalation to cover increasing costs. Such sources include: realistic fees for clinic program services; various forms of state grants, private institution programs, tuition subsidies; foundations; gifts; "industrial partnerships" outside the ophthalmic field; and innovative financing. PMID- 1287067 TI - Present status and projected needs of the educational facilities in optometry. AB - Optometry is affected by political, social and economic forces. Optometric leaders must understand that the issues of health care reform, education reform and economic reform can only be met through cooperation of all professionals, educational associations, as well as individual institutions. With good management, innovative use of available funds, and development of personnel, optometry can overcome contracted revenues and prosper through this decade. However, there is no doubt that educational reform is at the doorstep of the health care professions. Optometry must strive to face its challenges now and into the remaining years of this decade. PMID- 1287068 TI - The pros and cons of developing additional schools and colleges of optometry. AB - There are no manpower studies to give hard statistics of the number of practitioners needed now and in the future. We will still be increasing the number of optometrists in the country by maintaining the same course we are on now, and show no need for any new optometric schools or colleges. Yet, the present schools and colleges of optometry may need to expand or contract their entering class size as educational reform changes optometric education. PMID- 1287069 TI - What are the appropriate skills and knowledge of reimbursement systems needed for the entry-level practice of optometry? AB - Health care reimbursement has increasingly become a major factor in the day-to day practice of optometry. This paper, originally presented at the 1992 Summit on Optometric Education, outlines the various types of programs the optometrist should be familiar with, and emphasizes the importance of the integration of such knowledge into the curriculum of the schools and colleges of optometry. PMID- 1287070 TI - What is and what will be the need for formally educated optometric technicians? AB - The number of two-year degree optometric technician programs has drastically decreased in recent years. The main reasons are budget cuts common to higher education institutions and low enrollments. Two explanations for difficulty in maintaining full enrollments are lack of career awareness and low salaries. Are optometrists in private practice aware of this decrease and do they realize how much more difficult it will be in the future to hire formally educated employees? The optometric profession should evaluate its future personnel needs and address how those needs will be met. Time is of the essence since many of the remaining programs face a great risk of closing. PMID- 1287071 TI - The role of residency education by the year 2000. PMID- 1287072 TI - Non-steroidal anti-inflammatory drugs: current trends in pharmacology and therapeutics. AB - Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used for the chronic treatment of many inflammatory disorders. They are also used for the reduction of fever and mild to moderate pain. Because they are readily available to patients as both prescription and over-the-counter medications, it is likely that the practicing optometrist will encounter these agents in the practice setting. NSAIDS are associated with several common ocular and systemic adverse effects that include nonspecific conjunctivitis, blurred vision, allergic reactions and bleeding disorders. This article reviews the mechanism of action of NSAIDS as well as common or severe ocular and systemic side effects. PMID- 1287073 TI - Ontogeny of glutamine transport by rat liver plasma membrane vesicles. AB - Glutamine metabolism in the liver is essential for gluconeogenesis and ureagenesis. During the suckling period there is high hepatic protein accretion and the portal vein glutamine concentration is twice that in the adult, whereas hepatic vein glutamine concentration is similar between adult and suckling rats. Therefore, we hypothesized that glutamine uptake by the liver could be greater in the suckling period compared to the adult period. The present studies were, therefore, designed to investigate the transport of glutamine by plasma membranes of rat liver during maturation (suckling--2-week old, weanling--3-week old and adult--12-week old). Glutamine uptake by the plasma membranes of the liver represented transport into an osmotically sensitive space in all age groups. Inwardly directed Na+ gradient resulted in an "overshoot" phenomenon compared to K+ gradient. The magnitude of the overshoot was greater in suckling rats plasma membranes compared to adult membranes. Glutamine uptake under Na+ gradient was electrogenic and maximal at pH 7.5, whereas uptake under K+ gradient was electroneutral. Glutamine uptake with various concentrations of glutamine under Na+ gradient was saturable in all age groups with a Vmax of 1.5 +/- 0.1, 0.7 +/- 0.1 and 0.5 +/- 0.06 nmoles/mg protein/10 seconds in suckling, weanling and adult rats, respectively (P < 0.01). Km values were 0.6 +/- 0.1, 0.5 +/- 0.1 and 0.5 +/ 0.1 mM respectively. Vmax for Na(+)-independent glutamine uptake were 0.6 +/- 0.1, 0.55 +/- 0.07 and 0.54 +/- 0.06 nmoles/mg protein with Km values of 0.54 +/- 0.2, 0. +/- 0.1 and 0.5 +/- 0.2 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287074 TI - The development of corticosteroid binding globulin-like activity in fetal sheep blood. AB - Parturition in sheep is initiated by the fetus and is preceded by a rise in fetal cortisol and corticosteroid-binding globulin (CBG) late in gestation. In this study plasma cortisol and CBG concentrations were measured in fetal and maternal circulation from 40 days gestation to early post-partum. The fetal cortisol profile was shown to be triphasic in nature; being high in both the first and last trimester but low in the middle period of gestation. In the last trimester, total cortisol increased steadily, reaching it's highest level just prior to parturition (145 days gestation), before falling to maternal levels over the first 10 days post-partum. The changes seen in CBG concentrations throughout gestation and post-partum mirrored the triphasic nature seen in cortisol levels. CBG was significantly higher at 40, 56 and 140 days gestation than at mid gestation (77 and 90 days). However, at 145 days gestation there was a significant fall in CBG levels. CBG levels were higher at 1 day post-partum when compared to 145 days gestation, the former rapidly falling to maternal levels over the subsequent 9 days. The maximum binding capacity at 40, 56, 70 and 90 days gestation exceeds the total serum cortisol concentration. However at 140 and 145 days gestation and 1 day post-partum the total serum cortisol exceeds the Bmax. The highest cortisol:Bmax ratio is seen at 145 days gestation due to the fall of CBG binding capacity at this time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287075 TI - The retino-hypothalamic tract is involved in prolactin regulation in fetal sheep. AB - To investigate the role of the retino-hypothalamic tract on fetal prolactin regulation, we examined the effect of ocular enucleation on fetal plasma prolactin. Eleven fetuses of Suffolk ewes were chronically catheterized during fall, and six of them were subjected to bilateral ocular enucleation. All ewes were kept at 12h:12h light:dark cycle (lights on at 0800 and off at 2000). The experiments were performed 5-9 days after surgery (GA control fetuses 125 +/- 1.5, optical enucleation 121.3 +/- 1.5 days). Blood samples were taken from fetuses hourly around the clock, and plasma prolactin and cortisol were measured by radioimmunoassay (RIA). Luteinizing hormone (LH) and Growth hormone (GH) were measured in pooled plasma samples from control and enucleated fetuses by RIA. Average plasma prolactin was 5-fold lower in enucleated than in control fetuses (9.6 +/- 0.5 and 54.2 +/- 3.3 ng/ml, SEM; P < 0.005). Both control and enucleated fetuses presented circadian rhythm of prolactin with acrophase between 1400 and 1830 h. An enucleated fetus was tested for response of prolactin to TRH. Prolactin increased as described in the literature. There was no change in plasma concentration of cortisol, LH or GH after ocular enucleation. Our data indicate that the optical pathway participates in prolactin regulation in the fetal sheep. PMID- 1287076 TI - Renin-angiotensin and autonomic mechanisms in cardiovascular homeostasis during haemorrhage in fetal and neonatal sheep. AB - The present study examined the roles of the renin-angiotensin and autonomic nervous systems in cardiovascular homeostasis during slow progressive haemorrhage (20% of measured blood volume over 1h) in fetal (128-132 and 143-148 days gestation) and neonatal (5-9 and 12-20 days post-natal) sheep. Basal plasma renin activity (PRA) was not significantly different in the 4 sheep groups and increased to a similar degree (approximately 2 to 3-fold) during haemorrhage. Mean arterial pressure (MAP) exhibited modest falls in response to haemorrhage in all sheep groups and while heart rate (HR) was well maintained in the fetal groups there was a tendency to bradycardia in neonates. None of these responses was significantly different in age-matched fetal sheep subjected to bilateral vago-sympathectomy, cervical cord transection or bilateral nephrectomy, with the exception of PRA in the latter group which was close to zero throughout. Treatment with the angiotensin II (AII) antagonist, (Sar1-Ala8) AII (Saralasin), significantly increased basal PRA in both fetal and neonatal sheep (approximately 5 to 7-fold). The PRA response to haemorrhage was absent in neonatal sheep treated with Saralasin but significantly increased in fetal sheep. Saralasin significantly reduced resting MAP in both sheep groups and increased the hypotensive and bradycardic effects of haemorrhage in neonatal (approximately 3 to 5-fold) but not fetal sheep. It is concluded that in the perinatal period studied, fetal and neonatal sheep are equally well able to maintain cardiovascular homeostasis in response to moderate haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287077 TI - Glucocorticoids accelerate the ontogenetic transition of cardiac ventricular myosin heavy-chain isoform expression in the rat: promotion by prenatal exposure to a low dose of dexamethasone. AB - Cardiac myosin heavy chain expression undergoes a perinatal transition from predominance of beta-MHC to alpha-MHC. In the current study, we tested the effects of glucocorticoids in this early transition period, by treating pregnant rats with dexamethasone on gestational days 17, 18 and 19, using doses below (0.05 mg/kg), at (0.2 mg/kg) or above (0.8 mg/kg) the threshold for growth retardation. Cardiac MHC isoforms were resolved with a denaturing SDS-PAGE system, followed by quantitative densitometry. In normal animals alpha-MHC was only 10% of the total on gestational day 18 but rose to 35% by postnatal day 1, and to 95% by the end of the first month postpartum. During the early phase of this transition, the lowest dose of dexamethasone significantly promoted alpha MHC expression without inhibiting body or heart growth; regression analysis indicated a 40% increase in the slope of MHC isoform transition with respect to tissue weight. In contrast, the higher, growth-retarding doses of dexamethasone either failed to enhance alpha-MHC expression or caused biphasic changes, with inhibition at ages corresponding to the onset of weight deficits; regression analysis indicated that the effects of the higher doses on MHC could all be accounted for by changes in tissue weight. Glucocorticoid levels rise substantially in the period surrounding parturition, and serve to program the development and coupling of adenylate cyclase to membrane receptors; because adenylate cyclase has been shown to elicit the beta-MHC to alpha-MHC transition in vitro, our results suggest that glucocorticoids, along with thyroid hormone and beta-adrenergic stimulation, influence the ontogenetic program of MHC isoform transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287078 TI - Formation of vasculo-syncytial membranes in the human placenta. AB - Vasculo-syncytial membranes are localised areas of the placental villous membrane where the thickness of the barrier separating the maternal and fetal circulations is reduced to as little as 1-2 microns. Consequently, they are believed to be important sites for diffusional exchange. The morphological appearances suggest that they are caused by the obtrusion of locally dilated segments of the fetal capillaries into the trophoblast layer. This study sought quantitative evidence for the hypothesis by performing stereological analyses on vasculo-syncytial membranes at the electron microscopic level. The results confirmed that a strong relationship existed between the thickness of the capillary endothelium and that of the overlying stromal and trophoblastic tissue at these sites (r = 0.47, P < 0.001), indicating that some asymmetrical stretching or remodelling of the capillary wall was involved. Comparisons were also made between the thickness of the trophoblastic, stromal and endothelial components of the villous membrane in villi obtained from the central and from the peripheral parts of placental lobules, where vasculo-syncytial membrane formation is accentuated. The mean thickness of each component was lowest in the samples from the peripheral region, although the differences only proved to be statistically significant for the stromal layer (P = 0.01). Both sets of data lend quantitative support to the hypothesis that vasculo-syncytial membrane formation is the result of obtrusion of locally dilated segments of the fetal capillaries. The way in which this may be linked to changes in the dynamics of the fetal circulation as gestation advances is discussed. PMID- 1287079 TI - Effect of NH4Cl acidosis on the function of renin-angiotensin-aldosterone system in newborn infants. AB - The present study was undertaken to assess the influence of acute metabolic acidosis on the activity of renin-angiotensin-aldosterone system and renal function in a group of seven one-week-old neonates with mean birth weight of 2164 g (range: 1300-3750 g) and mean gestational age of 34 weeks (range: 28-40 weeks) undergoing oral NH4Cl load. NH4Cl was given in a dose of 2.8 mEq/kg to evaluate renal acidification. Prior to and following NH4Cl administration blood acid-base parameters, plasma urinary electrolytes, creatinine and aldosterone concentration as well as plasma renin activity, glomerular filtration rate, urine flow rate and net acid secretion were measured. NH4Cl administration significantly depressed blood pH (P < 0.05), total CO2 content (P < 0.01) and base excess (P < 0.01) and resulted in a significant elevation of plasma potassium concentration (P < 0.05). Furthermore, NH4Cl ingestion significantly increased urine flow rate, sodium, chloride and net acid excretion. In response to NH4Cl acidosis no consistent change in plasma renin activity and plasma aldosterone concentration could be detected. There was, however, an about 50% increase in urinary aldosterone excretion from the control value of 4.1 +/- 1.2 micrograms/day to 6.8 +/- 2.3 micrograms/day (P < 0.05) after NH4Cl administration. These data suggest that the responsiveness of neonatal adrenals to stimulation by metabolic acidosis is blunted, acidosis therefore, may play a minor role in the neonatal hyperfunction of renin-angiotensin-aldosterone system. PMID- 1287080 TI - Problems of AIDS in developing countries. PMID- 1287081 TI - Use and misuse of medical knowledge and technology. PMID- 1287082 TI - The effect of sulphonylurea therapy on serum total cholesterol and high density lipoprotein cholesterol. AB - A study was conducted on 50 cases comprising 25 patients of non-insulin dependent diabetes mellitus and 25 age and sex matched normal individuals. The diabetic state of the patients was controlled by glibenclamide, a sulphonylurea. The levels of serum total cholesterol and high density lipoprotein cholesterol were measured at the start and 15 and 30 days after glibenclamide therapy. There was a significant (p < 0.001) decrease in the levels of serum total cholesterol from initial 222.96 +/- 31.04 mg% to 218 +/- 28.99 mg% after 15 days and to 211.8 +/- 28.42 mg% after 30 days of therapy. In no case there was increase in serum total cholesterol level. There was a significant (p < 0.001) increase in the levels of serum high density lipoprotein cholesterol from initial 20.96 +/- 4.59 mg% to 21.8 +/- 4.78 mg% after 15 days to 23.72 +/- 5.07 mg% after 30 days of glibenclamide therapy and no case showed a fall in serum high density lipoprotein cholesterol level. This favourable alteration in serum total cholesterol and high density lipoprotein cholesterol was observed in patients of non-insulin dependent diabetes mellitus having ischaemic heart disease as well. PMID- 1287083 TI - Cervical status as a predictor of preterm labour. AB - A study was conducted on 140 pregnant women at and after 28 weeks of pregnancy for finding out the relationship of cervical length and position with onset of preterm labour. Incidence of preterm labour was significantly higher (p < 0.001) in women with central position of cervix (54.67%) than that with posterior position of cervix (10.77%). Onset of preterm delivery was closely related to cervical length of 2.5 cm or less irrespective of central (82.75%) or posterior (20%) position of cervix (p < 0.001). PMID- 1287084 TI - Role of histopathology in the diagnosis of tuberculous synovitis. AB - A study was conducted on 70 cases of tuberculous synovitis. Maximum number of cases were in the age group of 11-30 years (58.58%) with a male preponderance. Knee joint was found to be most commonly (57.12%) affected. Diagnosis of tuberculous synovitis was possible clinically in 75.72% and radiologically in 67.14% of cases only. Histopathological studies made on biopsy materials obtained from synovial membranes of the affected joints showed the presence of fibrosis, lymphocytic infiltration and epithelioid cells forming typical granuloma of tuberculous lesion. Proliferation of synovial membrane (92.85%), increased number of mast cells (82.95%) and caseation (78.57%) were observed. In all the cases the synovial membrane was of greyish white appearance. PMID- 1287085 TI - The reliability of urinary cytology in the detection of tumours of urinary bladder. AB - Detection of urinary bladder tumours by cytological examination of urine was carried out on 193 patients suffering from haematuria. The patients comprised 149 new cases and 44 follow-up cases previously diagnosed as bladder cancer. Urinary bladder malignancy was detected in 72 of new cases and 20 of follow-up cases by cytological examination of urine. Reliability of the findings was checked by histopathological examination of the biopsy material removed from bladder by cystoscopy which detected malignancy in 84 of new cases and 16 of follow-up cases. Thus the sensitivity of cytological examination of urine in detecting bladder malignancy was 92% and specificity of 88%. False positive result was 4% and false negative result was 12%. PMID- 1287086 TI - Prediction of recovery of Bell's palsy from clinical manifestations. AB - Sixty patients of Bell's palsy aged between 8 and 72 years, comprising 31 males and 29 females, were studied clinically to find out a method of prediction of recovery in early stage. It was found that young patients with incomplete palsy, unaccompanied by postauricular pain, loss of taste sensation over anterior 2/3rds of tongue hyperacusis and dry eye and recovery beginning within 4 weeks of onset of palsy are likely to make complete recovery, while older patients with complete palsy accompanied by severe postauricular pain, loss of taste sensation, hyperacusis and dry eye and beginning of recovery after 4 weeks of onset of palsy are most likely to have incomplete recovery. PMID- 1287087 TI - Tricuspid atresia with D-transposition and common atrium. PMID- 1287088 TI - Turner's syndrome and Down's syndrome in the successive children of a mother of advanced age. PMID- 1287089 TI - Electro-encephalography in current medical practice. PMID- 1287090 TI - Group surgical practice: a new approach to rural surgery. PMID- 1287091 TI - Consumer Protection Act and medical profession. PMID- 1287092 TI - Oral rehydration solutions: modifications. PMID- 1287093 TI - Velediction to Aesculapius. PMID- 1287094 TI - A study of urinary fistulae in Sokoto, Nigeria. AB - A retrospective study was conducted on 361 women to evaluate the factors influencing the development of urinary fistula. Primipara women (69.8%) in the age group of 15-19 years (51.52%) with a height less than 150 cm (68.14%) were most frequently affected. Prolonged labour (82.79%), spontaneous delivery (57.92%) and delivery by forceps and craniotomy (31.12%) were the most common obstetric causes. Operation by native doctors and lymphogranuloma venereum were responsible for 3.32% and 0.55% cases respectively. Juxtra-urethral fistulae (54.84%) were the commonest type and the size of fistulae ranged from 0.5-1 cm in 65.92% of cases. Of the associated conditions pelvic abnormality was most frequently (45.8%) observed followed by urinary tract infection (26.2%), ammoniacal dermatitis of vulva (22.19%), nerve palsy (20.26%), involvement of rectum and anus (10.5%), gynatresia (9.97%), cystolithiasis (7.4%), secondary amenorrhoea (4.15%) and pregnancy (3.1%). Absence of formal education and presence of poverty were observed in 95% and 75% of cases respectively. PMID- 1287095 TI - Fibrocalculus pancreatic diabetes in western Orissa. AB - Skiagram proved 35 cases of fibrocalculus pancreatic diabetes in order to analyse the clinical profile and its correlation with different descriptive epidemiological parameters were studied. Mean age was 25.17 +/- 7.85 years and male to female ratio was 6:1; 65.7% patients were poor (income < Rs 500 per month) and another 28.6% having average income (Rs 500 to Rs 1,000 per month); 74.3% came from rural areas having a family size of about > or = 7 members and sanitation was poor in all the cases. Mean body mass index was 15.93 +/- 3. Severe diabetes (ie, fasting blood sugar level > 251 mg%) and moderately severe diabetes (ie, fasting blood sugar level > 181 mg% but < 250 mg%) were noted in 51.4% and 11.4% cases respectively. Recurrent pain abdomen, infections, neuropathy, retinopathy, nephropathy and keto-acidosis were observed in 52.2%, 40.0%, 42.9%, 8.6%, 11.4% and 2.9% cases respectively. Mean soluble insulin requirement was 41.81 +/- 13.94 units. Four cases in whom pancreatic lithotomy was done, showed less insulin requirement and disappearance of pain. Parotid swelling, chronic diarrhoea and insulin resistance were not observed. Insulin requirement, epidemiological and biochemical parameters were similar to other young diabetics. PMID- 1287096 TI - Septic cavernous sinus thrombophlebitis: a review of 35 cases. AB - Thirty-five cases of septic cavernous sinus thrombophlebitis seen over the past 5 years are reviewed. Of these 80% were secondary to infection of the medial 1/3rd of the face. In more than 2/3rds of the cases the infecting organism was Staphylococcus aureus. Even with appropriate antibiotic therapy the overall mortality was 34.3%. PMID- 1287097 TI - Demographic survey of opinions towards smoking: a pilot study. AB - A survey was conducted by means of a questionnaire, on 865 smokers to analyse their opinions towards some general aspects of smoking. The subjects were mostly males (97.11%) and belonged to the age group of 21 to 50 years (80%). Heavy smoking is injurious to health is the opinion of most of the smokers (90.41%) particularly when maintained with other addictions (80%); tobacco is harmful not only when smoked but also when used in other forms (63%) and moderate smoking may not be much harmful (43%). However, smoking is not necessary to make or maintain relations with others (70%). Statutory warning has no marked effect on the habit (69.83%), the role of legal restrictions is dubious but advertisements encourage the habit definitely (62.54%). Three out of 4 persons know the problems of smoking and almost the same proportion of the people think that smoking can be stopped or at least checked. But there is difference of opinion about the person to be consulted, if any such problems arises from the habit of smoking. Family physicians may play an important role in controlling the habit. PMID- 1287098 TI - Vaginal hysterectomy: a new technique of vault closure. AB - The study was conducted on 200 patients undergoing vaginal hysterectomy at the Lokmanya Tilak Municipal General Hospital, Sion, Bombay over a period of 2 years from January 1988 to December 1989. A new technique of vault closure in 150 patients was compared with that of classical and Heaney's technique 25 cases each. Only 9.33% patients undergoing new technique belonged to the age group of 60 years and above. Out of 150 patients in the new technique 70 belonged to gravida III and IV. Using this new technique it was possible to decrease the average operative time by 5 to 15 minutes and the hospital stay by 2 full days. The postoperative febrile morbidity in the new technique group was 2.66% and 6 patients (3.99%) had significant haemorrhage. Three patients had vault infection contrasting with a significantly higher incidence in other two groups and 1.33% of cases (2/150) had fimbrial prolapse as against 12% incidence with Heaney's technique. PMID- 1287099 TI - Castleman's disease in the cervical lymph node. PMID- 1287100 TI - Naegele's pelvis causing obstructed labour. PMID- 1287101 TI - Persistent diarrhoea: an overview. PMID- 1287102 TI - Visceral larva migrans masquerading as liver secondaries. PMID- 1287103 TI - Problems with non-prescribed agents. PMID- 1287104 TI - Pain and addiction: an urgent need for change in nursing education. PMID- 1287105 TI - Diphenhydramine for nausea and vomiting related to cancer chemotherapy with cisplatin. PMID- 1287106 TI - Patient and nurse evaluation of patient-controlled analgesia delivery systems for postoperative pain management. AB - Five different patient-controlled analgesia (PCA) delivery systems were evaluated for the treatment of acute postoperative pain in 423 patients undergoing elective operations at a large tertiary care hospital. The PCA trial was conducted on four different postsurgical wards over a 5-mo period. All five devices were utilized on each ward for a 1-mo period. According to the nurses, the mean time (+/- SD) required to become comfortable using the Pharmacia Deltec CADD-PCA was significantly longer (50 +/- 37 min) than that using the Abbott Lifecare Plus (19 +/- 17 min), Bard PCA I (17 +/- 14 min), IVAC PCA (17 +/- 14 min), or Baxter PCA Infusor (7 +/- 8 min). With respect to ease of documentation by the nursing staff, the Baxter device was superior to the Pharmacia device. Similarly, mechanical problems were less frequent with the Baxter (6%) compared with the Pharmacia device (71%). The patients felt that the nurses were more comfortable using the Baxter device than the Pharmacia device. The patients also found the Baxter device easier to use, especially at night, and the least likely to interfere with ambulation. In conclusion, 80% of the nurses at this teaching center preferred the Baxter PCA Infusor over four widely used electronic PCA devices for the management of acute postoperative pain. The Pharmacia device was felt by the nurses to be less user friendly than the other programmable PCA devices used in this trial. Of the electronic devices we studied, the Bard and IVAC devices were the most cost-effective. PMID- 1287107 TI - Effects of a single oral dose of desipramine on postoperative morphine analgesia. AB - Drugs that block norepinephrine reuptake offer promise as opioid potentiators, because norepinephrine mediates opioid analgesia but not side effects such as sedation or nausea. In a two-by-two factorial design, we randomized 62 inpatients with pain following major surgery to receive either desipramine, 50 mg by mouth, or placebo at 6 a.m. on the first day after surgery. At their first request of pain medication after 8 a.m., they were given intravenous morphine, either 0.033 mg/kg or 0.10 mg/kg. Pain relief and side effects were assessed for 4 hr; peak relief on the visual analog scale (VAS) was the primary outcome variable. Pain relief, side effect scores, and time to remedication were significantly greater with the higher dose than with the lower dose of morphine, verifying assay sensitivity, but desipramine pretreatment did not significantly enhance morphine analgesia. The mean increase in peak VAS relief score after desipramine pretreatment, relative to placebo, was 6%; the 95% confidence interval for this estimate ranged from a 21% reduction to a 34% increase in pain relief. These results differ from a previous report that 1 week of pretreatment with desipramine, 75 mg per day, potentiated postoperative morphine analgesia. We conclude that if desipramine potentiation of opioid analgesia occurs in humans, its demonstration may require higher doses or chronic treatment. PMID- 1287108 TI - A survey of complications documented in a quality-control analysis of patient controlled analgesia in the postoperative patient. AB - Patient-controlled analgesia (PCA) has become a cornerstone of postoperative pain management in many institutions. Despite the extensive use of this analgesic technique, there are not large population studies to determine the frequency or types of complications associated with PCA in the literature. This study looks at 1122 patients over a 1-yr period. Eight significant complications associated with PCA use were noted during this period. These complications were attributable to overdosage (escalating dosage to meet patient analgesic needs or someone other than the patient administering drug through the PCA device) or to interaction of PCA drugs with concurrent medications. There was a much higher incidence of complications associated with PCA pumps featuring continuous infusion in addition to intermittent bolus compared with those employing intermittent bolus alone. The types of complications encountered in this survey demonstrate instances of PCA use that may present a higher risk to the patient and thus require closer monitoring. PMID- 1287109 TI - Pain profiles of patients with nonorganic chest pain: a preliminary report of the Multidimensional Pain Inventory. AB - The primary purpose of this report is to extend the range of the Multidimensional Pain Inventory (MPI) to include patients with nonorganic chest pain. Previous research with the MPI has not included this patient population, although this instrument has been used to derive an empirically based taxonomy of patient responses to chronic pain. Scale scores are provided for a sample of 43 chest pain patients and compared with normative scores from samples of chronic lower back pain patients and patients suffering from temporomandibular disorder. The MPI taxonomy was applicable for only 34.8% (N = 15) of this sample. Scale intercorrelations are examined and compared with those derived during development of the MPI, to explore reasons for this low classification rate. The results are discussed in light of cognitive-behavioral factors present in persistent chest pain, with implications for scale development and use of the MPI. PMID- 1287110 TI - Level of cancer pain knowledge among baccalaureate student nurses. AB - Inadequate nursing education is a major impediment to effective pain relief for cancer patients throughout the world. This study was conducted to identify the level of cancer pain knowledge among baccalaureate student nurses and to determine whether specific activities affect this level of knowledge. Two questionnaires were administered to 82 baccalaureate student nurses in the final course of their program. Although the students displayed a realistic perspective about the severity and prevalence of cancer pain and psychological dependence, specific knowledge deficits and negative attitudes suggest the possibility of inadequate pain management. Specifically, the students believed that (a) maximal analgesic therapy should be delayed until the patient's prognosis was less than 12 months; (b) the proportion of patients whose pain can be controlled by appropriate therapy is less than is possible; (c) increasing pain is related to tolerance rather than to progression of the disease; (d) the preferred route of administration is intravenous rather than oral; and (e) the degree of respiratory depression, rather than constipation, does not decrease with repeated administration. Significant positive correlations (P < or = 0.05) were found between age and cancer pain knowledge and between attendance at seminars/workshops and time spent reading professional journal articles. Of the 30% of the participants who perceived a particular person to be a source for obtaining information about cancer pain management, 52% specified a practicing registered nurse. Seminars and workshops were chosen by 59% of the students as the most effective way for nurses to increase their knowledge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287111 TI - Pain relief: the perspective of Catholic tradition. AB - Efforts to study patient care from the perspective of Catholic ethics date back four centuries. In the course of this history, a prominent issue has always been management of pain and the efforts to avoid pain. Thus, Catholic theologians were concerned about the effects of pain medication upon the psychic function and considered whether or not hastening death for suffering people was allowed and the ethical norms for using opioids to remove pain when death is imminent. Moreover, the issue of "overmedication" for difficult or elderly patients has been a concern. The President's Commission on Ethics in Medicine and Human Research has utilized many of the principles developed by Catholic theologians when considering the matter of pain relief for dying persons. PMID- 1287112 TI - Benzodiazepines for acute pain in children. AB - When pediatric pain is refractory and unresponsive to appropriate use of analgesic agents, there might be additional physical or psychologic dimensions of the pain that are not addressed by the analgesics. In addition to appropriate analgesic therapy, the psychologic needs of the child should be directly addressed and appropriate adjunctive physical modalities employed. Although benzodiazepines lack direct analgesic effects, they can reduce the distress associated with acute pain states by decreasing anxiety, insomnia, and muscle spasms that can be associated with acute pain. Intermediate or long-acting benzodiazepines in modest doses can be useful adjunctive agents when used short term for the treatment of selected acute pain complaints. In the highly distressed school-age child or adolescent with pain complaints relatively unresponsive to appropriate care, judicious use of benzodiazepines is worthy of consideration. PMID- 1287113 TI - Expression of IgA and IgM Fc receptors on murine T lymphocytes. AB - Fc receptors are induced on T cells following activation via the TCR. T cells that express Fc receptors transiently have the ability to use two different cognate systems: the TCR and immunoglobulins bound to the Fc receptors. The studies discussed in this article are focused on the Fc alpha and Fc mu receptors that can be induced on certain subsets of murine T lymphocytes. The article emphasizes the role of the T cell receptor for antigen in the expression of Fc alpha and Fc mu receptors on murine T cells and reviews experimental observations that suggest significant molecular heterogeneity of these Fc receptors. The finding that regulation of expression of Fc alpha receptors and Fc mu receptors on T lymphocytes is linked to cellular activation via the CD3/TCR complex implies that these Fc receptors might mediate important functions in the biology and pathology of T cells. PMID- 1287114 TI - Murine soluble Fc gamma receptors/IgG-binding factors (IgG-BF): analysis of the relation to Fc gamma RII and production of milligram quantities of biologically active recombinant IgG-BF. AB - The production of soluble forms of low-affinity Fc gamma R by cells expressing recombinant or natural membrane Fc gamma RII, and the structural relationships between these soluble receptors and membrane Fc gamma RII are described. We show that 37-40 kD soluble Fc gamma RII, corresponding to the two N-terminal domains of Fc gamma RII and binding to IgG, are spontaneously produced in vitro by cleavage of membrane Fc gamma RII. Moreover, we describe methods to produce and purify to homogeneity large quantities of endotoxin-free recombinant IgG-binding factor (rIgG-BF) from the culture medium of a cell line transfected with a mutated Fc gamma RII cDNA. These methods include the use of bioreactors for culturing transfected fibroblasts and the purification of rIgG-BF by ion-exchange chromatography and hydrophobic-interaction chromatography. By using such procedures, about 2.4 mg of rIgG-BF were purified from 1 liter of culture medium of transfected fibroblasts. Like natural IgG-BF, the 95-99% pure rIgG-BF suppressed, in a dose-dependent manner, secondary in vitro IgG antibody responses to sheep red blood cells. PMID- 1287115 TI - Regulation of the expression of murine alpha- and beta-Fc gamma R genes. AB - Murine low-affinity receptors for the Fc portion of IgG are of two types: Fc gamma RII and Fc gamma RIII. Murine Fc gamma RII and III have 95% homologous extracellular (EC) domains and bind the same ligands, but different transmembrane (TM) and intracytoplasmic (IC) domains. They, however, have unrelated TM and IC domains. Murine Fc gamma RII are single-chain receptors, encoded by the beta-Fc gamma R gene. Murine Fc gamma RIII are composed of two subunits: the ligand binding alpha-subunit, encoded by the alpha-Fc gamma R gene and the gamma subunit, encoded by another gene which belongs to a family of genes encoding dimeric subunits of multichain receptors. The expression of murine Fc gamma RII and Fc gamma RIII depends on a number of mechanisms which do the following: (1) determine the tissue-specific expression of the alpha- and beta-Fc gamma R genes by selectively unmethylating DNA in specific 5' sequences in different cell types; (2) regulate the initiation of the transcription of the alpha- and beta-Fc gamma R genes via several transcription factors; (3) up- and downregulate the amount of alpha- and beta-Fc gamma R transcripts in response to cytokines; (4) decide the alternative splicing of IC exons of the beta-Fc gamma R gene and generate the different Fc gamma RII isoforms; (5) possibly regulate the translation of alpha- and beta-Fc gamma R transcripts in different cells; (6) control the assembly of the Fc gamma RIII subunits and their membrane insertion, and (7) determine the turnover of Fc gamma RII and III in the presence and absence of ligands by affecting the internalization, shedding and proteolytic cleavage of the receptors. These mechanisms altogether contribute to make a variety of cells capable of responding differently to antigen-antibody complexes, depending on environmental stimuli. PMID- 1287117 TI - Fc gamma receptors: gene structure and receptor function. AB - Molecular studies of murine Fc gamma R have revealed much exciting new information about the structure and regulation of Fc gamma RI and Fc gamma RII genes and of the Fc gamma RI protein. The Fc gamma RI gene is composed of six exons, whereas the Fc gamma RII gene is composed of ten. The extracellular domains are encoded by individual exons in both genes (three in Fc gamma RI and two in Fc gamma RII); however, the Fc gamma RII gene shows greatest complexity in the region encoding the cytoplasmic tail and membrane spanning region, which is encoded by four exons compared to only one in the Fc gamma RI gene. Expression of Fc gamma RII is controlled by elements within the first 641 bases upstream of the transcription initiation site. The function of the domains of Fc gamma RI has been defined with the surprising finding that in the absence of the third domain the first two extracellular domains function as a broadly specific low affinity Fc gamma RII-like receptor. PMID- 1287116 TI - Fc gamma receptors in cancer and infectious disease. AB - Through interaction with antibody, IgG Fc receptors provide an interface between specific humoral immunity and Fc gamma R-bearing host cells. Fc gamma R trigger such diverse functions as immune complex clearance, phagocytosis of opsonized pathogens, reactive oxygen intermediate and enzyme secretion, and antibody dependent cellular cytotoxicity (ADCC). Moreover, Fc gamma R are the exclusive trigger molecules for tumor cell killing by human myeloid cells. Studies of Fc gamma R function have been aided by the use of bispecific antibodies to link cells or pathogens to specific host cell molecules, including Fc gamma R. These reagents have permitted determination of the role of Fc gamma R in ADCC of the protozoan, Toxoplasma gondii, by human effector cells. This approach has also indicated that Fc gamma R do not serve as entry points for viruses such as dengue virus and HIV. Taken together, these results provide insight into the utility of manipulating Fc gamma R function in the therapy of cancer and infectious disease. PMID- 1287118 TI - Functional capacity of Fc gamma receptor III (CD16) on human neutrophils. AB - Receptors for the Fc region of immunoglobulin G (IgG) are a structurally diverse group of molecules. Within the three Fc gamma R families (Fc gamma RI, Fc gamma RII and Fc gamma RIII), the presence of distinct genes and alternative splicing variants leads to a variety of receptor isoforms that are most strikingly different in the transmembrane and intracellular regions. An obvious example of structural variation in the transmembrane and cytoplasmic domains is observed in the Fc gamma RIII family. Fc gamma RIIIB, which is nearly identical to Fc gamma RIIIA in the extracellular domains, lacks both transmembrane and cytoplasmic protein domains and is anchored to the cell through a glycosyl phosphatidylinositol anchor. Analysis of Fc gamma RIII function presents a considerable challenge in understanding the role of different Fc gamma R receptors in polymorphonuclear neutrophil (PMN) function. While one hypothesis for the role of Fc gamma RIII in Fc gamma R-dependent PMN effector functions is that Fc gamma RIII serves as a binding molecule which focuses the IgG ligand for more efficient recognition and intracellular signaling by Fc gamma RII, recent observations from a number of laboratories suggest that Fc gamma RIII on PMN can transduce signals across the membrane independent of ligand-dependent engagement of Fc gamma RII. We will review these data and present recent data which suggest that the role of Fc gamma RIII extends beyond direct initiation of functions to a more complex role of synergistic receptor interactions. These findings will be reviewed in the context of the experimental approaches that have been used to examine the roles of Fc gamma RII and Fc gamma RIII on PMN function. PMID- 1287119 TI - Eosinophil IgE receptor and CD23. AB - In the present review, eosinophil Fc epsilon RII was compared to CD23, a differentiation marker of B cells. Biochemical analysis revealed that molecules of similar molecular weight were immunoprecipitated from eosinophils and B cells by an anti-CD23 monoclonal antibody (mAb) or by BB10, and anti-eosinophil Fc epsilon RII. By flow cytometry, a correlation was found between the binding of anti-CD23 mAb and myeloma IgE. However, a low expression of different epitopes of CD23 was observed in various hypereosinophilic patients. Northern blot analysis of eosinophil RNA with the cDNA probe of CD23 revealed a weak message in only 3 of the 6 patients expressing membrane CD23. The inhibition by anti-CD23 mAbs of IgE-mediated cytotoxicity and IgE binding to eosinophils clearly indicated the participation of CD23 or a related molecule in IgE-dependent eosinophil functions. However, the differential effects of anti-CD23 mAbs on eosinophils and B cells suggest major differences in the characteristics of the molecule expressed by eosinophils and by B cells. PMID- 1287121 TI - Receptors for IgA on phagocytic cells. AB - IgA receptors have been detected on monocytes, polymorphonuclear neutrophils (PMNs) and eosinophils, and on phagocytic cells at mucosal sites. These receptors bind both secretory and serum forms of immunoglobulin A (IgA) and require the Ca2 region of the IgA molecule for ligand recognition. Monocytes and PMNs modulate their expression of the IgA receptor upon treatment with cytokines, such as granulocyto-macrophage colony-stimulating factor, and lipopolysaccharide. Purified IgA receptors appear as heavily glycosylated molecules with an average molecular weight of 60 kD, dropping to 32 and 36 kD upon treatment with N glycanase. The cDNA sequence encoding the IgA receptor has been determined by expression cloning, and predicts that the receptor consists of two Ig-like extracellular domaines, a transmembrane region and a cytoplasmic tail of 41 residues. Ligation of IgA receptors on phagocytic cells by multivalent IgA complexes induces a variety of responses, including superoxide generation, release of inflammatory mediators, phagocytosis, and killing of various pathogenic microorganisms. Thus the apparent role of these receptors is to amplify the protective effects of the IgA antibody, a function of potential importance to mucosal defense. PMID- 1287120 TI - Expression, regulation and function of human Fc epsilon RII (CD23) antigen. AB - CD23, also known as the low affinity receptor for IgE (Fc epsilon RII), belongs to a novel superfamily of type-II integral membrane proteins. Fc epsilon RII expression was originally described on B cells but subsequent studies showed that CD23 is expressed on a variety of hematopoietic cells and is regulated by several cytokines (i.e., interleukin-4, interferons) in a tissue-specific manner. In some pathological conditions such as B-chronic lymphocytic leukemia, the CD23 gene is abnormally regulated resulting in CD23 overexpression. CD23 is not only an IgE receptor but also a membrane-bound precursor of soluble molecules that still bind IgE (sCD23 or IgE-binding factors). The functions of membrane CD23 are IgE dependent and vary according to the cell types on which it is expressed. In contrast, sCD23, in addition to being an IgE regulatory molecule, displays multiple cytokine activities that are IgE-independent. PMID- 1287124 TI - Are you liable for the medical malpractice of your co-owners? PMID- 1287125 TI - Medical staff bylaws: a double edged sword. PMID- 1287122 TI - FcR may function as a progression factor of nonlymphoid tumors. AB - Tumor progression is a multistep process involving genetic and epigenetic changes in a transformed clone. Some of these changes may be induced by host factors which may also select for transformed cellular variants with a high ability to survive and propagate. In this article we review studies showing that receptors for the Fc portion of IgG may be expressed on cells from human or animal tumors of nonlymphoid origin. We also review data demonstrating that at least with respect to cells transformed in vitro with Polyoma virus, transformation per se is not sufficient for the induction of Fc receptor expression. We also summarize preliminary data showing that Fc receptor expression is causally involved in conferring a high malignancy phenotype upon transformed cells. Possible mechanisms to explain these observations are discussed. PMID- 1287123 TI - In vitro inhibition of tumor B cell growth by IgG-BF-producing Fc gamma RII+ T cell hybridoma and by immunoglobulin G-binding factors. AB - The growth-modulating effect on mouse hybridoma B cells of IgG-BF-producing Fc gamma RII+ mouse T cell hybridomas and of the IgG-BF isolated from the culture supernatants of these cells has been examined. Cocultures of IgG-secreting hybridoma B cells with IgG-BF-producing T hybridomas or with partially purified IgG-BF demonstrated a reproducible inhibition of the tumor B cell growth. The inhibition was due to a cytostatic and not to a cytotoxic effect. Hybridoma B cells cultured in liquid medium in the presence of soluble IgG-BF, or cocultured in semisolid agarose assays with IgG-BF-producing hybridoma T cells did not undergo immediate cytolysis but were prevented from proliferating. Thus, our data indicate that IgG-BF-producing Fc gamma RII+ T cells interfere with the proliferation of transformed B cells, possibly through soluble IgG-BF. PMID- 1287126 TI - Practice automation: an essential, not luxury, tool. PMID- 1287127 TI - Factors affecting return to work after job-related injuries. PMID- 1287128 TI - Coronary heart disease in women: status 1992. PMID- 1287129 TI - Dehydroepiandrosterone protects mice inoculated with West Nile virus and exposed to cold stress. AB - The protective effect of pretreatment with dehydroepiandrosterone (DHEA) on stress-enhanced viral encephalitis was studied in mice exposed to cold following inoculation with West Nile virus (WNV). Exposure of WNV-inoculated mice to cold water (1 +/- 0.5 degrees C, 5 minutes/day for 8 days) resulted in a mortality rate of 83% as compared to 50% in nonstressed mice (p < 0.05). The effect of cold stress was more pronounced when mice were inoculated with WN-25, a noninvasive neurovirulent variant of WNV. Mice infected with WN-25 showed no mortality, whereas cold stressed mice inoculated with the same virus had a mortality rate of 67% (p < 0.05). The administration of DHEA (serial injections of 10-20 mg/kg with or without a loading dose of 1 gm/kg) resulted in a significant reduction in the mortality rate of stressed mice inoculated with either virus (p < 0.05). Virus levels in the blood and brain of the DHEA-treated mice, were significantly lower than in the control groups. DHEA also prevented the involution of lymphoid organs in stressed mice. The present study provides direct evidence of the protective effects of DHEA as an "anti-stress" agent. Its ability to prevent mortality associated with WNV or WN-25, and involution of lymphoid organs caused by stress induced immunosuppression, supports the notion that its activity is based on the modulation of the host response. PMID- 1287130 TI - Nested polymerase chain reaction for detection of human immunodeficiency virus type 1 DNA in clinical specimens. AB - A highly sensitive two-step polymerase chain reaction (PCR) method was evaluated for detection of human immunodeficiency virus type 1 (HIV-1) DNA in clinical specimens. The product resulting from the first amplification reaction is used as the template for the second PCR with an internal (nested) primer pair. Even when starting from a single copy of HIV-1 DNA, the double PCR product was readily detected by direct visualization in ethidium bromide-stained agarose gels. Amplification of minute amounts of HIV-1 DNA was successful in a considerable excess of HIV-1 negative DNA than reported previously. All of 85 HIV-1-infected individuals were PCR-positive with at least two of the three sets of primers used, 252 of 255 amplifications allowing unambiguous visualization of a unique DNA fragment of the expected size. The two-step amplification protocol is simple and rapid and fulfills the requirements of sensitivity and specificity for use in a clinical laboratory. PMID- 1287131 TI - Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction. AB - The prevalence of herpesvirus DNA was examined in inflammatory bowel disease tissue. DNA was extracted from resection and biopsy specimens of the large intestine from patients with ulcerative colitis (n = 21), patients with Crohn's disease (n = 29), and patients with noninflammatory bowel disease (controls) (n = 21). The nested polymerase chain reaction was used to detect viral DNA using primer pairs specific for either cytomegalovirus (CMV), herpes simplex virus 1 (HSV1), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), or Epstein Barr virus (EBV). HSV1 and VZV DNA were not detected in any of tissue samples. There was a high prevalence of CMV (81%), HHV6 (76%), and EBV (76%) DNA in ulcerative colitis tissue compared to Crohn's disease tissues (CMV 66%, HHV6 45%, EBV 55%). Control tissue had a relatively low frequency of CMV (29%) and EBV (19%) DNA but a prevalence of HHV6 DNA similar to that of ulcerative colitis (86%). However, the simultaneous presence of HHV6 and CMV and/or EBV DNA in ulcerative colitis tissue (76%) was much greater than in either Crohn's disease tissues (38%) or control tissue (29%) (P < 0.05). There was a low prevalence of CMV, HHV6, and EBV DNA in peripheral blood mononuclear cells from all patient groups. CMV and EBV are capable of reactivating HHV6: the high prevalence of coexistent HHV6 infection with either or both of these two viruses in ulcerative colitis tissue suggests that they may play a synergistic role in the pathogenesis of this disease. PMID- 1287133 TI - 1st Meeting of the Asian Pacific Society for Neurochemistry. Nagoya, Japan, October 22-23, 1992. Abstracts. PMID- 1287132 TI - Persistent delta antigenaemia in chronic delta hepatitis and its relation with human immunodeficiency virus infection. AB - The prevalence of persistent hepatitis delta (HD) antigenaemia and associated factors in patients with chronic infection with the hepatitis delta virus (HDV) were investigated. Among 157 consecutive patients known to be carriers of hepatitis B surface antigen (HBsAg), 36 (23%) had one serum marker of HDV infection (anti-HD and/or HDAg). Nine of the patients with an HDV marker were HDAg positive, including three who were anti-HD negative. A follow-up over a mean period of 13 months showed that five of five patients had a persistent HD antigenaemia. This serological profile was associated with the presence of antibody to the human immunodeficiency virus (anti-HIV) (P < 0.01), serum HIV antigen (HIVAg) (P < 0.2), and the female sex (P < 0.05). Persistent HD antigenaemia could be the consequence of the suppression of T cell cytotoxic activity against hepatocytes expressing HDAg, a lower humoral response, and/or hormonal factors. PMID- 1287134 TI - Imipenem and cefotaxime resistance: transduction by wild-type phages in hospital strains of Pseudomonas aeruginosa. AB - A wild-type bacteriophage appeared and was isolated from a Pseudomonas aeruginosa strain resistant to imipenem, cefotaxime, kanamycin and streptomycin (susceptible to carbenicillin, aztreonam, amikacin and fluoroquinolones). The best transducing properties were obtained with phage lysates prepared from bacteria growing on cefotaxime or imipenem. Transducing properties were found specific for individual recipient strain(s) susceptible to all drugs. A high-frequency of transduction was recorded for kanamycin and particularly for cefotaxime resistance determinants, followed by an imipenem determinant. This is now the fourth published wild-type bacteriophage, isolated from lysogenic nosocomial P. aeruginosa resistant to imipenem which was found to transduce this resistance determinant to susceptible pseudomonads. PMID- 1287135 TI - In vitro activity of cefpirome (HR 810) against enterococci and staphylococci. AB - The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecalis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lactam antibiotics. For E. faecalis, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 micrograms/ml, with an MIC50 of 8 micrograms/ml, and an MIC90 of 64 micrograms/ml. The optimal bactericidal activity against strains with MICs of < or = 8 micrograms/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations. Mec gene-negative staphylococci (both S. aureus and coagulase negative species) had cefpirome MICs of 0.25-2 micrograms/ml (MIC50 0.5 microgram/ml, MIC90 1 microgram/ml). Mec gene-positive strains had MICs of 0.5 128 micrograms/ml (MIC50 2 micrograms/ml, MIC90 32 micrograms/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high density inocula were used and after several passages in media containing the antibiotic. These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci. PMID- 1287136 TI - Antibacterial, antimycotic and trichomonicidal activity of a new nitroimidazole (EU 11100). AB - The antimicrobial profile of a new nitroimidazole derivative (5-nitro-1-methyl imidazolyl-2-hydroxy-3 terbutylphenyl carbinol) has been studied. The in vitro activity of the new molecule has been evaluated against both aerobic and anaerobic bacteria, Trichomonas vaginalis, and mycetes, under suitable experimental conditions. The new compound was compared with ampicillin against aerobic bacteria; with metronidazole against anaerobic bacteria, lactobacilli and T. vaginalis; with nistatin and econazole against candida and with econazole and bifonazole against filamentous fungi. The new nitroimidazole derivative has been shown to be moderately active against some anaerobic bacteria belonging to both the Gram-positive and Gram-negative groups. Its inhibitory activity against T. vaginalis was similar to that of metronidazole. PMID- 1287137 TI - Antimicrobial activity of benzydamine, a non-steroid anti-inflammatory agent. AB - The antimicrobial activity of benzydamine (BD), a non-steroid anti-inflammatory agent, was studied using different techniques against 38 strains belonging to 12 microbial species comprising bacteria, yeasts and a fungus. The minimum inhibitory concentrations, minimum lethal concentrations, per cent survivors after 30-minute exposure to BD (0.1%), growth curves of 7 selected organisms in subinhibitory BD concentrations and killing times for clinical isolates at different BD levels (0.05-0.15%) were determined. The data obtained throughout this study show that BD is a general antimicrobial agent with a rapid biocidal activity against a variety of organisms at concentrations less than those advocated for treatment of inflammatory conditions. PMID- 1287138 TI - The efficacy and safety of once-daily ceftibuten compared with co-amoxiclav in the treatment of acute bacterial sinusitis. AB - The efficacy and safety of a once-daily oral regimen of 400 mg ceftibuten was compared with oral co-amoxiclav 500 mg three times daily in a multicentre, single blind study. In patients with a bacteriologically confirmed infection, a successful clinical outcome was reported in 25 of 25 patients treated with ceftibuten and 10 of 10 patients treated with co-amoxiclav. In a further group of 88 patients, most of whom had been excluded from the primary efficacy evaluation because no pathogen was isolated pretreatment, overall successful clinical outcomes of 87% and 88% were reported for ceftibuten and co-amoxiclav, respectively. The duration of treatment and the time to resolution of the signs and symptoms of sinusitis were not significantly different in the two treatment groups. The incidence of adverse events was higher in the co-amoxiclav-treated patients (31% versus 15% in the ceftibuten group) as was the incidence of severe events (10% for co-amoxiclav-treated patients versus < 1% in the ceftibuten group). In summary, once-daily ceftibuten can be considered a safe and effective treatment for acute bacterial sinusitis. PMID- 1287139 TI - AIDS patients with bacterial lower respiratory tract infections: treatment with ofloxacin versus sulbactam-ampicillin. AB - In this open-label, randomized, parallel-groups study the Authors compare the parenteral administration of a beta-lactamase inhibitor associated with a semisynthetic penicillin (sulbactam-ampicillin) with the oral administration of a 3rd-generation quinolone (ofloxacin), in 20 HIV-infected subjects suffering from lower respiratory tract (LRT) infections. 12 patients were classified as AIDS, 6 as ARC (AIDS related complex) and 2 as asymptomatic seropositives. The risk of becoming HIV-infected and the work load for the health staff were also evaluated. The clinical and microbiological results indicate that oral ofloxacin is as effective as parenteral sulbactam-ampicillin for the treatment of LRT infections in HIV-positive individuals. In addition, the members of the health staff reported significantly less difficulty in administering ofloxacin in respect to sulbactam-ampicillin. PMID- 1287141 TI - Gamma-interferon enhances the cytotoxic activity of interleukin-2-induced peripheral blood lymphocyte (LAK) cells, tumor infiltrating lymphocytes (TIL), and effusion associated lymphocytes. AB - The effect of gamma-interferon (IFN-gamma) on the induction of interleukin-2 (IL 2) activated killer cell activity was studied: (I) in peripheral blood lymphocytes (LAK cells) from cancer patients and healthy donors, (II) in lymphocytes infiltrating solid tumors (TIL) from melanoma and breast cancer patients, and (III) in pleural effusion associated lymphocytes (EAL) from patients with lung adenocarcinoma. The coculture of LAK, TIL and pleural effusion mononuclear cells (MNC) with several doses of IFN-gamma (10, 50, 250, and 1250 U/ml) and a low dose of IL-2 (10 U/ml) for 5 days resulted in a synergistic effect on the cytotoxicity of these cells against several tumor cell lines. Furthermore there was a potentiation in the proliferation of MNC after a 5-day culture. The induction of lymphocyte cytotoxicity by a combination of IFN-gamma with low doses of IL-2 may be helpful in designing more effective cancer immunotherapeutic protocols with LAK, TIL or EAL. PMID- 1287140 TI - Fluconazole and ketoconazole in the treatment of oral and esophageal candidiasis in AIDS patients. AB - In our study 77 AIDS patients suffering from oral and/or esophageal candidiasis were evaluated: 38 received fluconazole, 39 ketoconazole. We analyzed the rates of clinical and mycological responses, relapses and toxicities. In vitro susceptibility tests for both antifungal drugs were performed by evaluating their Minimal Inhibitory Concentrations (MICs). The azole drugs investigated show a good activity in the treatment of oropharyngeal and esophageal candidiasis also in advanced stages of HIV infection. Clinical cure or improvement were achieved in 29 (76.3%) and 31 (79.4%) of the patients treated with fluconazole or ketoconazole respectively. Clinical or laboratory adverse experiences related to fluconazole were seen in 7 (21.2%) patients while ketoconazole provoked adverse experiences in 9 (26.4%) patients. In vitro susceptibility tests, if repeated more than once, both in primary infection and relapses, could be important to demonstrate a probable sensitivity change or resistance of the tested strains. PMID- 1287142 TI - Evaluation of toxicity in 22 patients treated with subcutaneous interleukin-2, alpha-interferon with and without chemotherapy. AB - Biological response modifiers (BRMs) have greatly modified the immunotherapy of tumors. Interleukin-2 (IL-2) has brought about metastasis regression in some cases of malignant tumors, however, when given systemically, it results in high toxicity. More recently, the subcutaneous administration of IL-2 (combined with alpha-interferon, alpha-IFN) seems to be capable of offering the same chances of therapeutic response, but this time with a lower level of toxicity. The Authors report an evaluation of toxicity in 22 patients treated with a combination of IL 2 + alpha-IFN i.m. with or without chemotherapy. The side-effects present in the majority of cases were: fever, diarrhea and asthenia. Approximately 50% of the patients had nausea/vomiting, mucositis, skin rashes, and slight leukopenia. The following side-effects were noted to a much lesser degree, thrombocytopenia, alterations in hepatic and dizziness and cystitis. Only one patient reached 4th degree toxicity, with mucositis, asthenia and skin rash. All the other patients received the treatment without suspensions for toxicity. Biological evaluations will enable us to determine in the future, the cases which can benefit from therapeutic intensification and thus it would seem opportune at this time to use therapy with acceptable toxicity. PMID- 1287143 TI - Radiotherapy and cisplatin in metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck. A phase II study. AB - 13 male and 8 female patients with metastatic squamous cell carcinoma (SCC) of an unknown primary tumor localized to the neck were treated with radiotherapy (RT) and cisplatin (CDDP). There were 12 (58%) and 9 (42%) patients, while no patient had N1 disease. All patients underwent biopsy. RT was given to all possible sites of the primary tumor (nasopharynx, pyriform sinus, and the base of the tongue). The RT dosage planned for the whole neck or supraclavicular area was 45 Gy, increasing to 60-70 Gy on the metastatic site. CDDP was given at a dose of 30 mg/m2, once weekly during the RT course. We observed 15 (72%) complete responses (CR) and 3 (14%) partial responses, while 3 (14%) patients did not respond to therapy. 12 (58%) patients are with no evidence of disease (NED) currently. The median survival time was 34+ months (range, 18+ to 50+ months). We observed two groups of toxicities: gastrointestinal and kidney toxicity. The majority of patients experienced grade 3 (RTOG) toxicity and no patient experienced grade 4 toxicity. This treatment appears to be effective and suitable for patients with metastatic SCC of an unknown primary tumor localized to the neck. PMID- 1287144 TI - Adhesion between the resin shell and composite resin. AB - Adhesiveness between the resin shell and composite resin was examined. As the resin shell, SR-PE-ISOCETTE, made from thermosetting crown and bridge resin, was used. The shear bond strengths between the resin shell and photocurable composite resin bonded by various methods were measured after 1-day of immersion in water at 37 degrees C. Super-bond C & B treatment to the resin shell effectively improved the adhesiveness, giving a bond strength of about 14 MPa. Clearfil new bond, Clearfil porcelain bond, Unifast and MMA/TBBO treatment gave almost the same bond strengths of about 7-9 MPa. Silane coupling agents were not effective for improving the bond strength. It was revealed that 4-META was necessary for obtaining good adhesion between SR-PE-ISOCETTE and composite resin. PMID- 1287145 TI - Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in periodontally healthy human subjects. AB - Age is known to be one of the factors which affect the rate of collagen and protein turnover in the connective tissues of the periodontium. The aim of the present study was to determine the levels of hydroxyproline (Hyp) and total protein in both the gingiva and gingival crevicular fluid (GCF) of periodontally healthy human subjects of two different age groups. The subjects of the young group were selected from among patients scheduled for extraction of upper and lower first or second premolars for orthodontic reasons. The second (older) group included individuals whose teeth were to be extracted for endodontic reasons. GCF was obtained before gingival sampling. The tissues surrounding the sockets were harvested immediately after extraction of the indicated teeth. All samples were analyzed biochemically. No significant difference was found in gingival and GCF levels of Hyp (which is unique to collagen) between the groups. Total protein levels in gingiva were significantly higher in the young group than in the older group. GCF total protein levels showed no significant difference between the groups. The higher gingival protein levels in the younger group seem to conform to previous findings. PMID- 1287146 TI - Investigation of surface corrosion in amalgam. AB - In this study, surface corrosion of carved and polished specimens of conventional and high-copper amalgams was investigated. The specimens were studied to detect surface corrosion after immersion in artificial saliva for 48 h or 1 year, and later investigated by SEM. Corrosion was greatest in 1-year-immersed carved conventional amalgam specimens. The surface was very rough with the contours of the particles visible and deep holes opening at the surface. High-copper amalgam specimens showed less corrosion than conventional amalgam specimens. PMID- 1287147 TI - Mutagenicity of analgesics, their derivatives, and anti-inflammatory drugs with S 9 mix of several animal species. AB - An investigation was undertaken to determine whether analgesics and their derivatives (13 compounds), and anti-inflammatory drugs (4 compounds) had mutagenicity. Rec-assay was used to clarify specific DNA-damaging properties, and the Ames test was used to find back-mutations, using S-9 fractions obtained from the liver of 4 animal species pretreated with polychlorobiphenyl. In the Rec assay, salicylic acid (2 mg), aspirin (5 mg), benzoic acid (4 mg), sulpyrine (0.4 mg), indomethacin (0.1 mg), oxyphenbutazone (0.1 mg) and diclofenac sodium (0.1 mg) showed a DNA-damaging tendency. In the Ames test, mutagenicity of methyl salicylate was demonstrated using the Salmonella typhimurium TA98 strain upon addition of hamster S-9 mixture. Weak mutagenicity was also found using the TA100 strain with rat S-9 mixture for salicylic acid, sulpyrine, indomethacin and oxyphenbutazone, and with hamster S-9 mixture for methyl salicylate, acetaminophen and phenacetine. PMID- 1287148 TI - Synthesis of radiopaque cyclophosphazene monomers, properties of bulk polymers and their application to composite resin. AB - A series of studies was conducted on the synthesis of polyfunctional cyclophosphazene monomers having radiopacity and a polymerization group in the same molecule, and their properties and applicability to composite resin were examined. Using octachlorocyclotetraphosphazene, P4N4Cl8 (4PNC), monomers were synthesized by replacing the 1-4 of chlorine (Cl) with p-bromophenol (BrC6H4OH, BrPh), and replacing the residual number of Cl, 7-4, with 2-hydroxyethyl methacrylate [CH2:C(CH3)COOCH2CH2OH](HEMA), so as to obtain four kinds of transparent monomer having radiopacity and a polymerization group in the same molecule. We then analyzed these monomers and examined their physical properties after bulk-polymerization. Next, we prepared an organic composite filler using 4PN-(BrPh)3-(EMA)5 monomer, which showed comparatively good radiopacity, to produce a new experimental radiopaque composite resin. Although radiopacity improved in accordance with the increase in the number of BrPh molecules replaced, the mechanical properties of the polymer became poorer. Similarly it was proved that the radiopacity of composite resin made with 4PN-(BrPh)3-(EMA)5 monomer was equivalent or even superior, compared with the radiopacity of the front tooth. Consequently, it was shown that these synthesized monomers can be applied to visible light-cured radiopaque composite resin. PMID- 1287149 TI - Blood flow to human gingiva measured by the 133Xe clearance technique. AB - Blood flow to the maxillary and mandibular gingivae was determined in 9 subjects under both normal conditions and in inflammation using the 133Xe clearance technique. A total of 36 sites (18 healthy and 18 inflamed) were selected for 133Xe injection. The clearance of radioactivity was monitored by a gamma camera. The calculated mean blood flows were 51.1 +/- 11.4 and 48.7 +/- 6.7 ml/100 g/min to the normal maxillary and mandibular gingivae, respectively. In inflamed gingiva, the corresponding mean blood flows were 55.0 +/- 13.0 and 54.7 +/- 11.7 ml/100 g/min, respectively. A statistical comparison of the healthy and diseased sites was done according to the paired t and Student's t tests. The difference between the sites was not significant (p > 0.05) in the maxilla, but significant (p < 0.05) in the mandible. There was no significant difference (p > 0.05) when the total healthy and diseased sites were compared. PMID- 1287150 TI - A case of adenocarcinoma arising in the upper lip. AB - A case of adenocarcinoma arising in the lip of a 20-year-old Japanese man is reported. After electro-irradiation therapy with a dose of 30 Gy, one third of the upper lip, including part of the cheek, was excised. Immediate reconstruction using transpositional flaps of the buccal skin and mucosa, and a functional neck dissection were performed. Nineteen months after surgery, there was no local recurrence or distant metastasis, and desirable results were obtained both functionally and cosmetically. PMID- 1287151 TI - Use of two miniplates for intermaxillary skeletal fixation in the treatment of jaw deformity and fracture. AB - Special techniques of skeletal intermaxillary fixation are described, which may be used in edentulous patients or those with many missing teeth or multiple fractures of the jaw. Two such cases are described in which the usual fixation techniques could not provide sufficient stabilization because of linguoversion and mesioversion or lack of teeth, resulting in inability to maintain a vertical interocclusal relationship. Two long eight-hole Champy miniplates were therefore used distally to the canines on both sides. In the first case, they provided fixation following a sagittal ramus osteotomy to advance the mandible, and in the second case they were used in the treatment of a mandibular fracture. PMID- 1287152 TI - Natural antibody against Thomsen-Friedenreich antigen in bovine milk. AB - The presence of natural antibody against Thomsen-Friedenreich (TF) antigen in fresh bovine milk was demonstrated by an enzyme-linked immunosorbent assay (ELISA). The amount of the antibody against TF antigen was decreased after heat treatment, and the antibody was not detectable by ELISA in the milk after pasteurization. A small amount of the antibody was detected in fetal bovine serum by ELISA, suggesting the transfer of passive immunity to the calf. PMID- 1287153 TI - Wear of denture teeth by use of metal plates. Part 3: Abrasive wear of posterior teeth and wear of opposing metal plates. AB - An in vitro evaluation of abrasive wear resistance of high-strength denture (HS) teeth and wear of metal plates (Pd alloy) on the opposing side was conducted. A total of 8 types of teeth were used in the experiments including 3 types of HS teeth, 3 types of conventional plastic denture (PL) teeth, porcelain teeth and metal teeth (Pd alloy). Sliding-induced wear tests were conducted by sliding these teeth over the metal plates. Abrasive wear resistance of the teeth was evaluated in terms of wear depth and weight loss. A comparison of wear depth showed that the abrasive wear resistance of HS teeth was 4.7 times that of PL teeth, 0.7 times that of porcelain teeth and 8.3 times that of metal teeth. Weight loss showed that the abrasive wear resistance of HS teeth was 3.3 times that of PL teeth, 0.2 times that of porcelain teeth and 11.4 times that of metal teeth. The weight loss of the metal plates was minimal when they slid over HS teeth, but increased in the order PL teeth, porcelain teeth and metal teeth. PMID- 1287154 TI - Periodontal health parameters in patients with chronic renal failure and renal transplants receiving immunosuppressive therapy. AB - The periodontal status of 54 renal transplant recipients and 52 patients with chronic renal failure receiving hemodialysis was evaluated and compared with that of systemically healthy subjects matched for age, sex, social status and the number of teeth present. The renal transplant recipients had been receiving immunosuppressive (IS) drug therapy since the time of transplantation. Both of the renal patient groups had significantly higher plaque index scores than the respective controls. By contrast, the renal transplant recipients showed significantly lower periodontal scores and pocket depths. However, there was no significant difference between the hemodialysis group and the corresponding healthy controls with regard to mean periodontal index score and pocket depth. No significant differences could be found among the three groups with regard to mean sulcular bleeding index score or gingival index score. Within the IS group, no relationship was found between the duration of drug therapy and the various periodontal parameters. The observed variations among the groups studied appear to suggest modulation of periodontal condition by both general health status in patients with chronic renal failure and the IS agents used in renal transplant recipients. PMID- 1287155 TI - Functional regulator therapy in treatment of skeletal open-bite. AB - A study was performed on the functional regulator, Frankel appliance (FR4) in order to test its efficiency in the treatment of patients with skeletal open bite. Pretreatment and post-treatment cephalometric evaluation was done on 11 patients and 10 untreated patients with skeletal open-bite. The results showed that the FR4 appliance was mainly effective on changes in dentoalveolar structures and produced no significant skeletal changes. The degree of anterior open-bite was decreased significantly in the treatment group in comparison with the controls (p < 0.01), due to vertical eruption of upper and lower incisors and retraction of maxillary incisors. PMID- 1287156 TI - A process for translating and testing a quantitative measure for cross-cultural nursing research. AB - A study was done to translate an English language, original measure of human behavior into Mandarin Chinese. A process used to translate from one language to the other is explained. Internal consistency of both versions of the measures is tested and equivalence across the two versions of the measure was supported. PMID- 1287157 TI - Jewish women and nursing: an overview of early history. AB - This paper seeks to fill a gap in nursing historiography by presenting an overview of the historical presence of Jewish women in nursing. The topic is viewed within the context of women's history and of nursing history. The authors identify several illustrious Jewish women whose contributions to nursing have earned them a place in the annals of the profession. It is hoped that this article will inspire studies about Jewish women in nursing today. PMID- 1287158 TI - Ethical practice in acute care nursing: are we there yet? AB - Ethical practice is a necessary component of nursing in today's complex clinical arena. This paper reviews the current status of ethics teaching in nursing education and the role of nurses in ethical decision making in acute care hospitals. PMID- 1287159 TI - Nurses' empathy and patients' satisfaction with nursing care. AB - Nurses' self-reported levels of empathy were studied in relation to patients' perceptions of satisfaction with nursing care received. Data were obtained from a volunteer sample of registered nurses and patients using two standardized, paper and pencil questionnaires: Empathy Construct Rating Scale and LaMonica/Oberst Patient Satisfaction Scale. No significant relationship was manifested between the variables under study. It was concluded that empathy training programs for nurses may not be necessary. In addition, although patients are generally satisfied with nursing care received in acute care settings, the data do not support a relationship between nurses' empathy levels and patients' satisfaction. Suggestions for further study are offered. PMID- 1287160 TI - Experimental infection with Scedosporium inflatum. AB - The experimental pathogenicity of Scedosporium inflatum (three isolates) and Scedosporium apiospermum (one strain) was determined following intraperitoneal and intravenous injection into immunosuppressed and normal mice. Immunosuppressed animals were treated with cortisone acetate. The results show that the strains studied displayed positive tropism to kidney and brain. In the histopathological study of the first organ, we initially observed abscesses at the glomerular level and later in the renal pelvis. In the brain, we detected large areas with necrosis, which produced important neurological disorders resulting in convulsive movements and a stiff neck. The isolates of S. inflatum were more virulent (45% mortality) than S. apiospermum (16% mortality). The inoculation method did not significantly affect the mortality rate of the mice by either fungus. In infections caused by S. inflatum the percentage of immunosuppressed mice which died was higher in comparison to that of the untreated group. On the other hand no differences were observed in the mortality of either group animals inoculated with S. apiospermum. PMID- 1287161 TI - Growth response of several Candida albicans strains to inhibitory concentrations of heavy metals. AB - Prolonged exposure of several Candida albicans strains to inhibitory concentrations of Cd, Cu, or Zn resulted in the appearance of resistant colonies at frequencies and with kinetics significantly different than expected based solely upon the predicted spontaneous mutation rate. Characteristics of the response included: (i) a delay usually of 4-10 days in the emergence of the first resistant colonies; (ii) continued accumulation of resistant colonies for a minimum of 21 days after initial exposure to selection; and (iii) final mutation frequencies ranging from 7.0 x 10(-6) to 9.8 x 10(-4). Further examination of the response of one of the strains to Cd, demonstrated that pretreatment with either ultraviolet irradiation or hydroxyurea resulted in approximately a 10-fold increase in the number of resistant colonies detected. While the distribution and identity of colony phenotypes was altered for all strains after exposure to the heavy metals, no specific morphologies could be correlated to development of resistance. PMID- 1287162 TI - Enhanced phagocytosis and intracellular killing of Candida albicans by GM-CSF activated human neutrophils. AB - Little is known about effector cell modulation regarding phagocytosis and candidacidal activities of human neutrophils in response to granulocyte macrophage colony stimulating factor (GM-CSF). In neutrophil monolayer assays, pre-treatment of cells with ultrapure GM-CSF at 40 Units ml-1 for a minimum of 1 h showed a significant enhancement of phagocytosis of Candida albicans (phagocytic index of 2.6 compared with 1.6 for unactivated neutrophils) after a 20 min ingestion period (P < 0.001). By counting viable colonies 50% of intracellular yeast cells were killed by non-activated neutrophils following internalization for 2 h. Neutrophils activated for 2 h with 40 Units ml-1 of GM CSF killed 90% of intracellular blastoconidia (P < 0.02). These results demonstrate that in in vitro assays GM-CSF enhances phagocytosis and intracellular killing of C. albicans. PMID- 1287163 TI - Iron assimilation in Cryptococcus neoformans. AB - We studied the effects of iron chelators and of a thallium salt on growth of Cryptococcus neoformans in defined medium. An oxidant-sensitive mutant strain was found to require exogenous ferric iron for growth. Using this strain, we found that the synthetic iron chelator, N-hydroxyethylenediamine triacetate (HEDTA), in several saturation states, stimulated growth as well as the comparably saturated siderophore deferoxamine. This non-specific result makes the existence of a cryptococcal ferrihydroxamate receptor doubtful. The catechols, caffeic acid, L 3, 4-dihydroxyphenylalanine, epinephrine, gallic acid, 3-hydroxytyramine (dopamine) and norepinephrine, were tested for growth stimulation in iron deprivation, under conditions in which deferoxamine was stimulatory. Catechols were found to be either neutral or inhibitory. The ferrous iron chelator, bathophenanthroline disulfonate (BPDS), inhibited growth strongly in the absence of exogenous iron, suggesting that ferric ion must be reduced before it can be internalized. Direct evidence of extracellular reduction was provided by accumulation of red-coloured ferrous-BPDS complex. The inhibition caused by BPDS was relieved by ferric HEDTA, even in the presence of 10-fold increased BPDS, suggesting a second, low-affinity, non-reductive iron uptake pathway. This inference was further supported by the observation that toxicity of the non reducible ferric analogue, thallium (III), is relieved by iron repletion. PMID- 1287164 TI - Interaction of terbinafine with human serum and serum proteins. AB - The allylamine antimycotic terbinafine acts by inhibition of ergosterol biosynthesis at the level of squalene epoxidase. Using this mechanism in Candida parapsilosis cells, a functional assay was developed to investigate the effects of serum and serum proteins on the antifungal action of terbinafine and related drugs in vitro. Inhibition of ergosterol biosynthesis by terbinafine was antagonized by human serum in a dose-dependent non-saturable manner. The results were not affected by varying the period of pre-incubation of serum with the drug or with the fungal cells, or by performing the test in other species of Candida, Aspergillus and Trichophyton. Qualitatively similar effects were observed with the related allylamine compounds naftifine and SDZ 87-469, the extent of antagonism correlating with their lipophilicity. The effect appeared to be caused by non-specific binding of the drug to major serum components, including albumin and the lipoproteins (both LDL and HDL). Reduced bioavailability resulting from binding by serum may at least partly account for the low efficacy of terbinafine in experimental models of systemic infection, in contrast to its high efficacy in infections of the skin, nails and hair. PMID- 1287165 TI - Contact sensing in Candida albicans: a possible aid to epithelial penetration. AB - Hyphal development in the dimorphic pathogenic fungus Candida albicans is thought to facilitate the primary invasion of surface epithelia during superficial infections. When mycelia were grown on Nuclepore membrane filters that were placed over serum-containing agar, the hyphae grew over the membrane surface and through the pores thereby crossing to the other side of the membrane. Hyphae that did not contact the lip of a pore did not enter it. The response was likely to be due to contact guidance (thigmotropism) and not chemotropism towards the nutrients since hyphae growing on the underside of the membrane also entered the pores then grew away from the underlying nutrient agar. The response therefore seems to be due to sensation of the substrate topography, and tropic movement in relation to changes in contour. This behaviour may enable the hyphae to penetrate epithelia at microscopic wound sites, membrane invaginations and other foci where the integrity of the epithelium is weak. PMID- 1287166 TI - Fungemia observations of peripheral tissue clearance in humans. AB - Patients with fungemia, mainly due to Candida albicans, had cultures repeated from arterial and venous sites to determine yeast cell clearance during fungemia. Of the 48 patients, 37 had repeat positive cultures (36 arterial and venous samples; one venous culture). Additionally, 24 patients had arterial and venous samples cultured quantitatively. An average of 9.1 colony forming units (CFU) ml 1 was isolated from arterial samples and 5.5 CFU ml-1 from venous samples (60% of arterial, P < 0.01). This suggest that arterial fungal densities exceed venous densities and that peripheral tissues clear 40% of yeasts. PMID- 1287167 TI - Quantitation and morphotyping of Candida albicans from healthy mouths and from mouths affected by erythematous candidosis. AB - Imprint culture and a mouthwash method were used to determine if quantitative differences exist between isolates of Candida albicans from individuals with healthy oral mucosa and from patients with erythematous candidosis (EC). The C. albicans isolated were differentiated by morphotyping. No quantitative difference in yeast isolations was observed with either technique irrespective of tobacco smoking status, the presence of a prosthesis, or EC. Multiple morphotypes were isolated from smokers with upper dentures and from smokers and non-smokers with EC, whilst a single morphotype was isolated from non-smokers with a healthy oral mucosa. PMID- 1287168 TI - Activation of human complement system Paracoccidioides brasiliensis and its deposition on the yeast form cell surface. AB - The yeast form of Paracoccidioides brasiliensis strain Pb18 was able to activate C3 of normal human serum diluted in phosphate-buffered saline or EGTA-MgCl2 in vitro. C3 convertase was also permissive when Pb18 cells were pre-treated with a pool of immune serum from patients with paracoccidioidomycosis and incubated in serum diluted in EDTA-CaCl2. The components C3, and fragments C3c, C3d, C3g, factor H, factor B, C4 and C5b-9 were demonstrated on the Pb18 cell surface by immunofluorescence although no effect was seen on fungal viability. PMID- 1287169 TI - Quantitative preservation of viability of Aspergillus fumigatus. AB - Quantitative preservation of the viability of two isolates of Aspergillus fumigatus was studied over a 15-month period of storage. Significant loss of viability occurred in isolates preserved at -70 degrees C in both phosphate buffered saline with Tween (PBST) and 0.1% gelatin, immediately, and between 6 and 15 months. Storage in 10% and 25% dimethyl sulphoxide at -70 degrees C was successful up to 8 weeks with gradual loss of viability later. PBST at 4 degrees C or room temperature, or 10% glycerol at -70 degrees C maintained 100% viability of the cultures up to 6 months and 15 months, respectively. To preserve 100% viability, long-term storage of A. fumigatus is best done in 10% glycerol in PBST at -70 degrees C compared with the other methods tested. PMID- 1287170 TI - Oculomotor nerve palsies in children. AB - Fifty-four patients with oculomotor nerve palsy who presented over a 21-year period at our institution were reviewed retrospectively. There were 38 isolated third nerve lesions, and 16 with additional cranial nerve involvement. Eleven cases were congenital in origin, and 43 were acquired. Of the acquired group, 31 were traumatic, 7 infection-related, 3 attributed to migraine or other vascular causes, and 2 neoplastic. Average follow up was 36 months. The congenital lesions were predominantly right-sided; amblyopia, although common, responded well to treatment. Trauma and bacterial meningitis accounted for more cases of isolated oculomotor nerve palsy than seen in the previous literature. In distinct contrast to the adult population, no cases of diabetes, posterior communicating artery aneurysms, metastatic tumors, or pituitary lesions were found. PMID- 1287171 TI - The ocular manifestations of the Sturge-Weber syndrome. AB - Sturge-Weber syndrome (SWS) is a rare neuro-oculocutaneous disorder. The ocular component manifests as glaucoma and vascular malformations of the conjunctiva, episclera, choroid, and retina. The authors reviewed the records of and recalled for examination 51 consecutive patients with a diagnosis of SWS seen at The Hospital for Sick Children, Toronto, Ontario, Canada, from 1980 to 1991. Of the 51 patients, 36 (71%) had glaucoma, 26 experienced onset before 24 months of age and the remainder after 66 months of age, 35 (69%) had conjunctival or episcleral hemangiomas, and 28 (55%) had choroidal hemangiomas, which were bilateral in 12 patients. Other ocular manifestations (retinal vascular tortuosity, iris heterochromia, retinal detachment, and strabismus) also occurred. Thirty-four of 51 (67%) glaucomatous eyes had a final visual acuity of 20/40 or better, or central, steady, and maintained fixation in each eye. PMID- 1287172 TI - An alternative approach to the surgical management of exotropia--the unilateral lateral rectus recession. AB - Fifty-five patients with moderate angle exotropia of 15 to 20 prism diopters were surgically treated with a unilateral lateral rectus recession of 7.0, 7.5, or 8.0 mm. The mean age at surgery was 14.5 years. The mean preoperative deviation was 18.0 delta. The mean lateral rectus recession was 7.6 mm. At the initial postoperative follow up, all patients were either a small-angle exotropia or esotropia, or orthophoric. Twenty-eight of the 55 patients (51%) were orthophoric at their most recent follow up. Twenty-four patients (44%) were undercorrected, with 22 of these having residual exodeviations less than 8 delta. Three patients (5%) were overcorrected. PMID- 1287173 TI - Pattern of childhood blindness and partial sight among Jordanians in two generations. AB - A study of 260 Jordanians who became blind or visually impaired (according to World Health Organization standards) before the age of 15 years showed the dominant effects of genetically determined causes in two generations. Genetic causes were responsible for the visual impairment in 122 (77.7%) of 157 subjects in the group born after 1970 and for 69 (67%) of 103 in the group born before 1970. There was a statistically significant change in the overall pattern (genetic and acquired causes) of blindness between the two generations, and there was also a significant change in the pattern of acquired blindness alone. A decrease in corneal infections leading to blindness or visual disability in the younger generation was accompanied by an increase of trauma in the same age group. Parental consanguinity in those with genetically determined causes of visual impairment was high compared with those with nongenetic causes (79% vs 33.3%, P < .05). The autosomal recessive mode of inheritance was the most common pattern encountered (53.9%). PMID- 1287174 TI - Severe visual deficits in infancy in northern Israel: an epidemiological perspective. AB - The characteristics of 193 legally blind children ranging in ages from birth to 4 years were analyzed. The overall incidence was 1/1000 live births; however, the ethnic specific incidence varies. All children were diagnosed before the age of 20 months and the most frequent alerting sign was lack of visual tracking. In 33.3%, the deficit was first suspected by a family member. A genetic etiology accounted for 38% of the cohort. The relative risk for an associated handicap was significant as well as the rate of hospitalizations for apparently unassociated diseases. It appears that both prevention and early detection could be achieved by a risk index. PMID- 1287175 TI - Multiple congenital contractures (arthrogryposis) in association with Peters' anomaly and chorioretinal colobomata. PMID- 1287176 TI - Peters' anomaly: a clinicopathologic study. AB - Two infants were born with bilateral Peters' anomaly. The first baby was a girl, born prematurely at 35 weeks of gestation and who died 8 days later. The second infant was a boy, born at 38 weeks of gestation, who had severe conotruncal abnormality of the heart. Both babies had distinctive facial dysmorphism and severe central nervous system abnormalities including partial or complete absence of the corpus callosum and cerebral calcifications. Biochemical and genetic investigations showed no abnormalities in either child and there was no family history of genetic disorders. Neither case showed evidence of an intrauterine infection. Postmortem ocular findings in the first infant included bilateral herniation of the ruptured cataractous lens into the posterior corneal defect, iridocorneal adhesions, persistent hyperplastic primary vitreous, and total retinal detachment. The left eye of the second infant was eviscerated at 11 months of age because of recurrent, spontaneous perforation. Pathologic ocular findings included large fragments of lens material adherent to the posterior corneal stroma through a large central defect in Descemet's membrane and endothelium, fibrovascular proliferation of the adjacent corneal stroma, and iridocorneal adhesions. PMID- 1287177 TI - Tonic pupils associated with neuroblastoma. PMID- 1287178 TI - Oculoauricular dysplasia syndrome of Goldenhar and Peters' anomaly: a new association. PMID- 1287179 TI - Inferior rectus muscle contracture resulting from perinatal orbital trauma. PMID- 1287180 TI - Testing stereopsis. PMID- 1287181 TI - Single-dose kinetics of primidone in human subjects: effect of phenytoin on formation and elimination of active metabolites of primidone, phenobarbital and phenylethylmalonamide. AB - Effect of repetitive administration of phenytoin (PHT) on the single-dose pharmacokinetics of primidone (PRM) was investigated in 3 healthy male subjects. The peak concentration of unchanged PRM was achieved at 12 and 8 h after the administration of PRM in the absence and the presence of PHT, respectively. The elimination half-life of PRM was decreased from 19.4 +/- 2.2 (mean +/- S.E.) to 10.2 +/- 5.1 h (p < 0.05) and the total body clearance was increased from 24.6 +/ 3.1 to 45.1 +/- 5.1 ml/h/kg (p < 0.01) in the presence of PHT. No significant change was observed for the apparent volume of distribution between the two treatments. In the absence of PHT, the measurable amount (> or = 0.1 mumol/l) of phenobarbital (PB) and phenylethylmalonamide (PEMA) did not appear in the serum until 5.3 and 1.3 h after the PRM administration, and the peak concentrations of PB and PEMA were achieved at 52 and 36 h, but the concentrations of both metabolites were very low (PB 1.3 mumol/l; PEMA 1.7 mumol/l). In the presence of PHT, within 0.8 and 0.5 h after the administration of PRM, the derived PB and PEMA appeared in the serum. About a 6-fold increase in the peak concentrations of both the metabolites were observed (PB 8.2 mumol/l; PEMA 11.0 mumol/l). No significant changes were observed for the elimination half-lives of both PB and PEMA in the absence and presence of PHT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287182 TI - Activation of hepatic microsomal glutathione S-transferase of rats by a glutathione depletor, diethylmaleate. AB - The effect of glutathione depletor diethylmaleate on rat hepatic glutathione S transferase and glutathione peroxidase was studied in vivo and in vitro. When diethylmaleate (600 mg/kg) was given i.p. to rats, liver glutathione was depleted within 2 h and recovered to the control level 5 h after diethylmaleate treatment. Both glutathione S-transferase and peroxidase activities in microsomes, not in cytosol, were markedly increased during glutathione depletion and only glutathione S-transferase activity remained at high levels after recovery of the glutathione content. The increase in microsomal glutathione S-transferase and peroxidase activities with concomitant exhaustion of glutathione was also observed by perfusion of the isolated liver with diethylmaleate (10 mM). When liver microsomes were incubated with diethylmaleate in vitro at 37 degrees C, glutathione S-transferase, but not peroxidase, activity was increased; the increase was not reversed by dithiothreitol. These results indicate that diethylmaleate activates microsomal glutathione S-transferase by direct reaction to the enzyme during glutathione depletion and suggest that glutathione S transferase activity and glutathione peroxidase activity in the microsomal enzyme may be differently regulated. PMID- 1287183 TI - Mechanisms of intestinal absorption of the antibiotic, fosfomycin, in brush border membrane vesicles in rabbits and humans. AB - In order to clarify the mechanism of intestinal absorption of an antibiotic, fosfomycin (FOM), the uptakes of FOM by rabbit and human small intestinal brush border membrane vesicles (BBMV) were studied. The initial uptake of FOM by BBMV at 15 s was saturable at a higher concentration of FOM. The kinetic parameters at 37 degrees C of the saturable uptake expressed by the Michaelis-Menten equation were Kt = 5.17 mM and Jmax = 3.88 nmol/15 s/mg protein for rabbits, and Kt = 4.03 mM and Jmax = 1.90 nmol/15 s/mg protein for humans. The most efficient uptake was observed in the presence of both inward-directed Na(+)- and H(+)-gradients in both mammals. The uptake of FOM was inhibited by inorganic phosphate, FOM glycol which is a degradation product of FOM in the gastric juice and specific inhibitors of phosphate transport such as arsenate and phosphonoacetic acid. These findings confirmed that FOM absorption from rabbit and human small intestines is associated with the phosphate transport system. These transport phenomena of FOM are in close agreement with those obtained previously in rat BBMV studies. Judging from the results obtained for three mammalian species, rat, rabbit and human, it was concluded that carrier-mediated transport via the phosphate transport system is a very important pathway of intestinal absorption of FOM. PMID- 1287184 TI - Clastogenicity of aporphine alkaloids in vitro. AB - The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was carried out on 19 aporphine alkaloids including apomorphine with and without rat liver homogenates (S9) mix. Eighteen of 19 alkaloids tested induced chromosomal aberration in the presence or absence of S9 mix. Among the alkaloids tested, anolobine, liriodenine and 4,5-dioxodehydrocrebanine induced chromosomal aberrations at relatively low concentrations and as low as 2.5, 5 and 3.13 micrograms/ml, respectively. Dicentrine, anolobine and 4,5-dioxodehydrocrebanine induced chromosomal aberrations with high frequencies. Apomorphine induced 10% aberrant cells at 12.5 micrograms/ml in the direct method and 12% at 100 micrograms/ml with S9 mix in the S9 method. Liriodenine which was the most potent mutagen for TA100 with S9 mix and roemerine which was the most potent for TA98 with S9 mix in Ames test were also clastogenic with and without S9 mix. PMID- 1287185 TI - Electrical stimulation-evoked release of endogenous taurine from slices of the hippocampus, cerebral cortex and cerebellum of the rat. AB - Release of endogenous taurine by electrical stimulation of slices of the hippocampus, cerebral cortex, cerebellum and medulla oblongata of the rat was studied and compared with that of alanine and/or gamma-aminobutyric acid (GABA). Electrical stimulation caused a calcium-dependent release of taurine from slices of the hippocampus, cerebral cortex and cerebellum but not from slices of the medulla oblongata. The stimulus-evoked release of taurine in the hippocampus was rapid in onset and declined to baseline fast, which was essentially similar to the time course pattern of the stimulus-evoked release of GABA. In addition, there were distinct regional differences in the relative amounts of taurine released. Electrical stimulation did not release alanine from any regions examined. These results support the hypothesis that taurine plays a neurotransmitter role in the hippocampus, cerebral cortex and cerebellum of the rat. PMID- 1287186 TI - Evaluation of a new penetration enhancer 1-[2-(decylthio)ethyl]azacyclopentan-2 one (HPE-101). AB - A new compound, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101) was synthesized, and its skin penetration enhancing activity was examined by using 14C-indomethacin as a penetrant. A solution of HPE-101 and indomethacin was applied to a cloth pad affixed onto an adhesive tape to give a HPE-101 patch, and the patch was applied to hairless mouse skin. The amount of percutaneously absorbed indomethacin was determined by measuring the radioactivity excreted in urine for 24 h after application. 1) Azone and decylmethyl sulfoxide, enhanced markedly the percutaneous absorption of indomethacin when the propylene glycol ethanol (9:1 v/v) mixture was used as the solvent. 2) Among various penetration enhancers dissolved in the indomethacin solutions and applied to screen for penetration enhancing activity, HPE-101 was found to be the most prominent. 3) Solvents containing more than 3% (w/w) of HPE-101 produced a plateau level of the penetration enhancing activity. 4) Daily application of 1% (w/w) solutions of HPE 101 or Azone increased the daily excretion of indomethacin significantly above the level excreted on the previous day. However, repeated daily application beyond 3 d gave a steady state excretion of indomethacin. 5) The mouse skin was pretreated with 3% (w/w) solutions of HPE-101 or Azone for 24 h on the 1st day, and the indomethacin solution was applied for 24 h on the 3rd day and 7th day to examine the recovery of skin barrier function. Enhanced excretion of indomethacin was still noted on the 3rd day, but enhancement was not observed on the 7th day. PMID- 1287187 TI - Enantioselective oral bioavailability of 0-isovaleryl propranolol as a potential prodrug of propranolol. AB - The enantioselective oral bioavailability of propranolol (PL) from 0-isovaleryl PL was determined and compared with parent PL in beagle dogs. The bioavailability of the individual enantiomer from the prodrug increased about 2 fold. The AUC ratio between the S(-)- and R(+)-isomer posed at 0.89 which was statistically not different from that obtained after administration of PL alone. These features indicate that 0-isovaleryl-PL promises to be a potential prodrug of PL from the pharmacokinetic and pharmacodynamic point of view. PMID- 1287188 TI - Overestimation of the lipoprotein fractional catabolic rate (FCR) measured in short duration experiments. AB - The aim of the study was to compare two methods classically used in rats to determine the fractional catabolic rate (FCR) of labeled high or low density lipoproteins: constant infusion and single pulse. The FC of [14C]-sucrose HDL (High density lipoprotein) was studied. For the short term experiment (8 hours), both methods gave similar FCR determined 8 hours after HDL constant infusion (9.4%.h-1 +/- 0.6) or single pulse (8.5%.h-1 +/- 0.4), values significantly higher than those measured 24 hr after the single pulse (6.2%.h-1 +/- 0.3). The identification and simulation of the model representing HDL movements between an intravascular and extravascular pool, after single pulse and constant infusion methods, demonstrated that FCR of lipoproteins cannot be precisely measured with techniques involving excessively short observation periods. PMID- 1287189 TI - An oral melatonin replacement regimen that re-establishes the normal circadian levels of urinary 6-sulphatoxymelatonin in functionally pinealectomized rats. AB - Wistar rats maintained on a 12-hr daily photoperiod (LD 12:12 cycle) exhibited a diurnal rhythm in urinary 6-sulphatoxymelatonin (aMT6s) concentrations with peak levels in the scotophase. Light-induced functional pinealectomy (FPX) abolished the nocturnal rise in aMT6s, lowering it to photophase levels. The objective of the study was to formulate an oral melatonin replacement regimen that would restore a normal rhythmic output of urinary aMT6s in functionally pinealectomised rats. Three regimens of sequential doses of melatonin were tested. Of these, the regimen with melatonin concentrations of 4 ng, 12 ng, 65 ng, and 4 ng per ml of drinking water given to rats during the 1st, 2nd, 3rd, and 4th 3-hr periods, respectively, of the 12-hr FPX phase, was found to generate a urinary aMT6s level that closely resembled the natural level and rhythm exhibited under an LD 12:12 cycle. This dose is considered appropriate to restore certain melatonin-mediated physiological functions in Wistar rats subjected to FPX. PMID- 1287190 TI - Entrainment of the circadian rhythm in the rat pineal N-acetyltransferase activity by melatonin is photoperiod dependent. AB - Entraining effect of melatonin on the circadian rhythm in rat pineal N acetyltransferase (NAT) activity was studied under various photoperiods. Melatonin administration prior to dark onset for 5 successive days phase-advanced the evening NAT rise under the light:dark (LD) cycle of either LD 10:14 or LD 8:16, but not under LD 12:12. It is assumed that under the latter regime, the end of a light period exhibited a phase-delaying effect on the NAT rise. The light exposure appeared to be a stronger Zeitgeber than melatonin itself. Data show that melatonin applied in the late light period advances the evening NAT rise under a short photoperiod only; under a longer photoperiod, the phase-advancing effect of melatonin may conflict with a phase-delaying effect of the end of a light period, and the effect of light exposure overrides that of melatonin. PMID- 1287191 TI - Inhibitory influence of late afternoon melatonin injections and the counter inhibitory action of melatonin-containing pellets on thyroid growth process in male Wistar rats: comparison with effects of other indole substances. AB - Previous studies performed in our laboratory indicated that melatonin, when administered in late afternoon (1600-1800) as s.c. injections for 10 days, exerted an inhibitory effect on thyroid growth in mice and Sprague-Dawley rats. The goal of the present study was to examine the effects of melatonin and other indole substances (5-methoxytryptophol, N-acetylserotonin, 6-methoxytryptamine), administered for 10 days, for either 4, 8, or 10 weeks, on thyroid growth processes in adult male Wistar rats. We have also compared the action of melatonin administered in late afternoon as s.c. injections with effects of the melatonin-released chronically from s.c. implanted beeswax pellets containing 1 mg of the hormone. Additionally, the effects of melatonin injections in animals with the pineal gland removed and in thyroid stimulating hormone (TSH)-injected rats have been studied. We examined the mean mitotic activity rates (MMARs) of thyroid follicular cells (TFC) and the wet thyroid weights. We concluded that melatonin, of the examined substances, is the most potent inhibitor of thyroid growth; the hormone reduced the MMAR of TFC and the thyroid weight at all time points. 5-Methoxytryptophol, like melatonin, exerted the inhibitory influence on the mitotic activity; however, it did not affect thyroid weight. The influence of other indole substances was much less pronounced. It was shown that melatonin pellets prevented the inhibitory effect of late afternoon melatonin injections on thyroid growth processes. This observation is consistent with results of other authors concerning the counter-antithyroid effect of melatonin on thyroid hormone secretion. Pinealectomy revealed the stimulatory effect on thyroid growth processes, while melatonin treatment reversed the effect of the surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287193 TI - The pineal gland of the trumpet-tailed rat (Octodon degus). AB - The structure and ultrastructure of the pineal gland of the degu or trumpet tailed rat (Octodon degus), a rodent inhabiting tropical-equatorial areas, was examined under light and electron microscopy. On the basis of its form, size, and location, the pineal gland of the degu is classified as a proximal or "A" type. The connective tissue appeared poorly developed and the gland contained non fenestrated capillaries. A single population of typical pinealocytes was found. In addition, a small number of glial cells and cells with electron dense bodies appeared scattered throughout the gland. Cells with dense granules were found isolated or forming small groups always in close proximity to blood vessels. Numerous sympathetic nerve fibers with small dense-core vesicles were found. Also, some myelinated nerve fibers were observed. The physiological significance of the presence of large electron-dense granules in some pineal cells and their particular location around the blood vessels in discussed. PMID- 1287192 TI - Serum prolactin and luteinizing hormone levels and the activities of hypothalamic monoamine oxidase A and B and phenylethanolamine-N-methyl transferase are changed during sexual maturation in male rats treated neonatally with melatonin. AB - Male rat pups were given a single dose of melatonin on day 5 of age. On days 30, 45, and 60, prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were measured in serum and monoamine oxidase A (MAO A) activity, monoamine oxidase B (MAO B), and phenylethanolamine-N-methyl transferase (PNMT) activity were measured in the hypothalamus. Melatonin administration increased serum PRL levels at all ages studied. Serum LH levels were decreased in the melatonin treated group on day 30, but levels were elevated on days 45 and 60 of age as compared to controls. LH response to luteinizing hormone-releasing hormone (LHRH) only increased in melatonin treated animals at 30 days of age. Serum T levels decreased with melatonin treatment at 30 days of age, but increased on days 45 and 60 of age. T response to human chorionic gonadotropin (hCG) was blunted by melatonin treatment at 30 days of life. Hypothalamic MAO A activity increased, after neonatal melatonin administration, at 30 and 45 days of age and decreased at 60 days of life. Early neonatal melatonin administration increased MAO B and PNMT activities on day 45. These findings suggest that neonatal melatonin administration induces an earlier sexual maturation in male rats, possibly related to PRL, LH, MAO, and PNMT increases. PMID- 1287194 TI - Melatonin concentration in the umbilical artery and vein in human preterm and term neonates and neonates with acute fetal distress. AB - In order to assess the existence of a rhythmic secretion of melatonin (aMT) in newborns and whether this rhythm is affected by neonatal stress, we studied 112 newborns classified in three groups: normal babies delivered at term, preterm infants born before the 38th week, and babies with fetal distress. Melatonin was measured by RIA in the umbilical artery and vein at the time of birth. Melatonin levels in umbilical arterial and venous blood showed a diurnal rhythm in all groups. Melatonin levels in umbilical cord artery and vein were closely related. Nocturnal melatonin levels were increased in newborns with acute fetal distress in comparison with normal term and preterm neonates. These results suggest that (1) a rhythm of aMT secretion exists in newborns, although it cannot be determined whether this rhythm is of maternal or fetal origin and (2) neonatal stress (acute fetal distress) increases aMT production during the night in comparison with normal term and preterm neonates. PMID- 1287195 TI - Models for describing absorption rate and estimating extent of bioavailability: application to cefetamet pivoxil. AB - Five absorption rate models have been compared for describing cefetamet data in 34 adults after oral administration of cefetamet pivoxil with food alone or in combination with either an antacid or an H2 antagonist. A sequential zero- then first-order input process provided the most flexible description of the absorption rate of cefetamet. If the first-order rate constant is linked to the zero-order input parameters the model can be interpreted as the consequence of solubility-limited absorption. While a sequential input is theoretically reasonable to assume, the first-order process appeared to be independent of the zero-order input. A population-based approach was applied to estimate the effect of dose and gastric pH increase on absorption and disposition. There appeared to be a dose-associated change in several parameters. The most marked change was an increase in volume of distribution of cefetamet. Treatments expected to increase gastric pH slowed the first-order component of the absorption process. Three models for estimating the extent of bioavailability have been compared using observations from 18 adults and 13 children receiving iv cefetamet and oral cefetamet pivoxil on two separate occasions. The most consistent estimates of the disposition parameters and the extent of bioavailability were achieved with the sequential zero- and first-order model under the assumption that steady state volume of distribution and nonrenal clearance were the same after iv and oral treatment. PMID- 1287196 TI - Variational analysis of the transdermal delivery rate from two prototypical ethanol-water nitroglycerin TTS devices and Transderm-Nitro 10 in the normal population. AB - The performance of two prototypical ethanol-water flux-enhanced transdermal therapeutic systems were compared to the performance of commercial Transderm Nitro 10. This was a single-center, open-label, three-treatment, randomized crossover study in six healthy subjects who completed the study. Concurrent with each transdermal treatment, an infusion of the stable isotope [15N]3 nitroglycerin was administered. The use of double isotope methodology was incorporated into this study to minimize the variation introduced by fixed-effect error on the evaluation of transdermal flux. The objectives of this study were to isolate experimentally and characterize the average flux enhancement of each prototype, to determine the temporal profile of delivery, and to evaluate the components of variance of drug delivery from each transdermal system. The results of this study showed that the two flux-enhanced transdermal systems with different fill volumes both produced flux enhancement factors of 2 to 3 relative to Transderm-Nitro 10. Prototype B demonstrated a 57% reduction in intersubject variation relative to Transderm-Nitro 10 indicative of enhanced control of drug permeation across a subject population. Prototype A, while reducing intersubject variations, was less than optimal. Both prototypes demonstrated comparable intrasubject variation relative to Transderm-Nitro 10, indicating similar stability for within-subject transdermal drug delivery. The flux enhancement and variational properties of Prototype B were consistent with those intended based on mechanistic considerations of mutual nitroglycerin and ethanol-coupled transdermal delivery. PMID- 1287197 TI - Salbutamol disposition and dynamics in conscious rabbits: influence of the route of administration and of the dose. AB - This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 micrograms/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 micrograms/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 micrograms/kg), total plasma clearance was 82 +/- 5 ml/min per kg, apparent volume of distribution was 5.0 +/- 0.5 l/kg, and terminal half-life was 41 +/- 2 min. Similar values were estimated when 120 micrograms/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80 +/- 0.19, 0.48 +/- 0.22, and 0.78 +/- 0.46 mmol/l, and for the second group, maximal decrement was 1.31 +/- 0.37, 0.70 +/- 0.24, and 0.84 +/- 0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po > it > iv.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287198 TI - Fundamental pharmacokinetic limits on the utility of using a sinusoidal drug delivery system to enhance therapy. AB - Clinically, it is known that some disease states respond to drug treatment in a cyclic manner. This has resulted in qualitatively, or empirically, determined cyclically varying drug treatment studies which have been shown to improve therapeutic response in some cases. A theory is developed, for drugs that can be described by pure catenary pharmacokinetic models, which enables one to quantitatively determine at what time a cyclic infusion of drug should be initiated, what the frequency of infusion should be, and what the amplitude of the infusion should be to obtain maximum therapeutic benefit at steady state. Also, the theory allows one to determine quantitatively a priori if a drug's pharmacokinetics precludes the possibility of any real advantage to be gained by cyclically infusing the drug. To implement the theory, it is assumed that the drug obeys linear pharmacokinetics and that the desired pharmacological response is rapid and approximately proportional to a pharmacokinetic compartmental concentration. In particular, a linear system analysis approach is applied to drugs obeying linear pharmacokinetics. It is found that at steady state the amplitude of the sinusoidally varying component of drug's compartmental concentration can be expressed as the amplitude of the rate of infusion times the magnitude of the compartment's transfer function. In addition, an expression for the shift in phase (lag time) of the compartmental drug concentration, relative to the input infusion, is obtained. For a one-compartment model, or for a compartment containing the site of infusion, the amplitude of the sinusoidally varying component ultimately declines in direct proportion to the period (T) of oscillation and the lag time increases from 0 to -0.25T as the period decreases. At a short enough cyclic infusion period, the lag time increments by an additional value of -0.25T, and the attenuation in sinusoidal amplitude decreases by an additional factor of T, for each compartment sequentially connected down the chain from the compartment receiving the infusion. This theory is then applied to the drugs, 5-fluorouracil, KS1/4-DAVLB, theophylline, and adriamycin to see if sinusoidal modulation of the infusion rate would be of therapeutic benefit. The theoretical predictions are then compared to clinically determined empirical results and shown to be consistent. In general, it is shown that the micro rate constants describing the drug's pharmacokinetics must be large (i.e., the system must be able to respond rapidly) for sinusoidal infusion to be of value. PMID- 1287199 TI - Bias and variance of extrapolated tails for area-under-the-curve (AUC) and area under-the-moment-curve (AUMC). AB - The usual formulas for the extrapolated values of AUC and AUMC from tn to infinity produce estimates that are biased. An empirical correction factor is shown to reduce both bias and variance of estimates. The fitted value Cz at the last time-point tn should normally be used in the formulas, rather than the measured concentration Cn. Nonlinear least squares methods offer no advantage over the fitting of a straight line to ln (C). PMID- 1287200 TI - Building population pharmacokinetic--pharmacodynamic models. I. Models for covariate effects. AB - One major task in clinical pharmacology is to determine the pharmacokinetic pharmacodynamic (PK-PD) parameters of a drug in a patient population. NONMEM is a program commonly used to build population PK-PD models, that is, models that characterize the relationship between a patient's PK-PD parameters and other patient specific covariates such as the patient's (patho) physiological condition, concomitant drug therapy, etc. This paper extends a previously described approach to efficiently find the relationships between the PK-PD parameters and covariates. In a first step, individual estimates of the PK-PD parameters are obtained as empirical Bayes estimates, based on a prior NONMEN fit using no covariates. In a second step, the individual PK-PD parameter estimates are regressed on the covariates using a generalized additive model. In a third and final step, NONMEM is used to optimize and finalize the population model. Four real-data examples are used to demonstrate the effectiveness of the approach. The examples show that the generalized additive model for the individual parameter estimates is a good initial guess for the NONMEM population model. In all four examples, the approach successfully selects the most important covariates and their functional representation. The great advantage of this approach is speed. The time required to derive a population model is markedly reduced because the number of necessary NONMEM runs is reduced. Furthermore, the approach provides a nice graphical representation of the relationships between the PK-PD parameters and covariates. PMID- 1287201 TI - Smooth nonparametric maximum likelihood estimation for population pharmacokinetics, with application to quinidine. AB - The seminonparametric (SNP) method, popular in the econometrics literature, is proposed for use in population pharmacokinetic analysis. For data that can be described by the nonlinear mixed effects model, the method produces smooth nonparametric estimates of the entire random effects density and simultaneous estimates of fixed effects by maximum likelihood. A graphical model-building strategy based on the SNP method is described. The methods are illustrated by a population analysis of plasma levels in 136 patients undergoing oral quinidine therapy. PMID- 1287202 TI - Sample size determination for bioequivalence assessment using a multiplicative model. AB - In bioequivalence studies Cmax and AUC serve as the primary pharmacokinetic characteristics of rate and extent of absorption. Based on pharmacokinetic relationships and on empirical evidence, the distribution of these characteristics corresponds to a multiplicative model, which implies a logarithmic normal distribution in the case of a parametric analysis. Hence, consideration is given to exact and approximate formulas of sample sizes in the case of a multiplicative model. PMID- 1287203 TI - Hepatitis B surface antigen screening in a nonindigent population. AB - The recommendation for universal screening of all pregnant women for hepatitis B surface antigen (HBsAg) is based on data from publicly funded hospitals. We retrospectively reviewed screening results of 2,696 mothers who delivered between May 1989 and April 1990. Our population was 85% privately funded. Screening for HBsAg was positive in 0.07%, negative in 80.4% and not done in 19.6%. All positive screens would have been identified by screening only patients with recognized risk factors. We conclude that the sensitivity of identifiable risk factors to detect HBsAg carriers may be high in some populations. We speculate that universal screening in these populations is not cost efficient. PMID- 1287204 TI - Effects of induced menopause on Burch colposuspension for urinary stress incontinence. AB - The clinical and urodynamic short term results after colposuspension for urinary stress incontinence has been studied in a group of young patients in whom menopause was induced surgically and compared with a similarly treated group who did not undergo surgical castration. Clinically, no differences were found in the incidence of diurnal frequency, nocturia, urgency, urge incontinence or stress incontinence between the groups. No urodynamic changes in the cystometric, uroflowmetry and urethral pressure profile measurements were found post operatively between the two groups. It is concluded that surgically induced menopause in the absence of aging has no effect on the results of colposuspension for urinary stress incontinence in the short term. PMID- 1287205 TI - Neugebauer-Le Fort operation for vaginal prolapse. A review of 38 cases. AB - Thirty-eight patients with varying degrees of vaginal wall prolapse were operated on using the Neugebauer-Le Fort technique. Their ages ranged from 59 to 90 years. Grand multiparity (> 4) was relatively uncommon (26%). Symptoms were present for more than two years in over half of the women. Serious medical conditions requiring preoperative attention were present in 55% of patients. If the uterus was present, dilation and curettage (D&C) was performed prior to the operation. Intraoperative complications were virtually absent; however, minor postoperative complications occurred in 30% of the patients. None of these complications were related to surgery or altered discharge plans. There were no deaths. No recurrences of prolapse were reported among 30 patients who were followed. PMID- 1287206 TI - Laser laparoscopy versus laparotomy in lysis of pelvic adhesions. AB - Severe adhesions were induced at laparotomy by laser ablation of the surface of one uterine horn and 1 cm2 of pelvic sidewall in 20 rabbits. Three weeks later the rabbits were selected at random for laparoscopy or laparotomy. Adhesions at the horn, sidewall and incidental sites were scored and lysed with laser at similar power densities. Three weeks later animals were killed and adhesions were blindly scored. We found a significant and similar reduction in severe adhesions at uterine horns after either laser laparoscopy or laser laparotomy, better lysis of sidewall and incidental adhesions by laser laparoscopy and formation of de novo adhesions at nonoperative sites after laparotomy but not after laparoscopy. We conclude that (1) de novo adhesions are common after laparotomy; (2) severe uterine horn adhesions can be reduced equally well by both laparoscopy and laparotomy but laparoscopy is superior to laparotomy with less severe peripheral adhesions; (3) outcome of adhesiolysis depends on several variables, including adhesion density and location and approach (laparotomy or laparoscopy), even when the tool (laser) is constant. PMID- 1287207 TI - Confidentiality in the age of AIDS. AB - Confidentiality is a fundamental rule of medicine and has been specifically defined in many codes of medical ethics. A changing clinical environment both because of diseases such as AIDS, which were not anticipated when these clinical codes were created, and because of the changing relationship between the physician, the patient, and the payor for the physician's care creates dilemmas concerning the rule of confidentiality. PMID- 1287208 TI - Variability of serum gonadotropin and dehydroepiandrosterone sulfate concentrations in women with polycystic ovary syndrome. AB - This study was designed to assess the variability of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandrosterone sulfate (DHEAS) levels over time in women with polycystic ovary syndrome (PCOS). Serum LH, FHS and DHEAS concentrations were determined for four consecutive monthly intervals in three groups of women: group 1, normal cycling women in the follicular phase (n = 9); group 2, normal cycling women in the luteal phase (n = 10); and group 3, women with PCOS (n = 11). For LH, DHEAS and the LH/FSH ratio, a histogram was constructed based on whether the subjects in each group had 0, 1, 2, 3 or 4 high values. In addition, the coefficient of variation (CV) for the four individual values of each hormone was determined for each subject to quantitatively assess the variability of measurement over time. Histographic analysis revealed that an elevated LH value or an elevated LH/FSH ratio in PCOS was inconsistent. For DHEAS, 9 of 11 PCOS subjects had either 0 (n = 7) or 4 (n = 2) high values, suggesting that such determinations are relatively consistent. We conclude that (1) isolated LH or LH/FSH measurements may not be sufficiently reproducible to be clinically useful despite evidence that LH values may be more stable in PCOS than in normal women and (2) a normal or high DHEAS value in PCOS is more likely to be consistently replicated, although the number of subjects studied limits the power of this conclusion. PMID- 1287209 TI - Incidental finding of endolymphatic stromal myosis during luteinizing hormone releasing hormone agonist therapy for suspected benign uterine myomata. A case report. AB - A 39-year-old woman with an enlarging myomatous uterus underwent a three-month course of luteinizing hormone releasing hormone (LHRH) agonist treatment. Despite a 50% reduction in uterine size, pathologic examination after uncomplicated hysterectomy revealed a low-grade endometrial stromal sarcoma. As the use of LHRH agonists for myoma reduction increases, delay in the diagnosis of sarcomatous disease will become more widespread. With current available diagnostic modalities, differentiation between sarcomatous and myomatous growth within the uterus is difficult. The possibility of delay in the diagnosis of unsuspected sarcoma when using LHRH agonists is an inherent and apparently unavoidable complication in some cases. PMID- 1287210 TI - Pain during sexual response due to bilateral Bartholin's gland adenomas. A case report. AB - Benign adenomas of the major vestibular gland are very rare. Presented is a case of bilateral vestibular gland adenomas in a woman whose chief complaint was vulvar pain occurring with sexual arousal and orgasm. Surgical removal of the adenomas relieved the symptoms. The development of pain during sexual response in this case appears to be mediated by vascular engorgement. PMID- 1287211 TI - Immediate cerclage following delivery of one nonviable twin. A report of three cases. PMID- 1287212 TI - Prenatal detection and management of quadruple nuchal cord. A case report. AB - As imaging techniques improve, nuchal cords are often being identified prior to labor. Nuchal cords are encountered in up to 25% of deliveries and are usually not clinically significant. They may, however, have devastating results. Nuchal cords may be associated with abnormal fetal activity and testing, but there is often no clinical warning of a nuchal cord during pregnancy, labor or delivery. We report a case of a quadruple nuchal cord discovered after the mother complained of decreased fetal movement. The clinical course of this patient highlights many of the difficulties encountered in the management of antenatally diagnosed nuchal cords, particularly in the preterm fetus. PMID- 1287213 TI - Uterine prolapse after laparoscopic uterosacral transection. A case report. AB - Two cases of severe uterine prolapse are reported following laser uterosacral nerve ablation (LUNA). Both patients had a history of vaginal childbirth and subsequent development of secondary infertility and severe dysmenorrhea. It is suggested that this procedure be performed with caution on vaginally parous patients, and that it be reserved for use in patients who have adequate uterine support. Future studies are needed to determine the long-term incidence of uterine procidentia following this procedure. PMID- 1287214 TI - A continuous glucose monitoring system based on microdialysis. AB - The development of a system for continuous glucose measurement is described. A microdialysis fibre is used to continuously withdraw the glucose sample. After passing through the microdialysis fibre the perfusion liquid enters a micro enzyme reactor which is filled with immobilized glucose oxidase. The enzyme activity, which varies with the glucose concentration, is monitored by an oxygen electrode. The measuring system can be adapted to a desired dynamic range by varying the perfusion rate. The measurement system has been calibrated for two different perfusion rates and shows a linear response to glucose concentrations between 0-3.5 mmol at 12 microliters/min and 0-8 mmol at 25 microliters/min. A probe, which can be configured with different lengths of the dialysing fibre, has also been designed to enable subcutaneous insertion of the microdialysis fibre in clinical studies. Subcutaneous glucose sampling by means of microdialysis is suggested to be used in the design of a glucose monitoring device for clinical use. PMID- 1287215 TI - Multielectrode spiral cuff for selective stimulation of nerve fibres. AB - In this paper we present the modelling, design, and initial experimental testing of a nerve cuff multielectrode system for selective stimulation of fibres in superficial peripheral nerve trunk regions which is capable of making a selective activation of multiple muscles. The developed multielectrode nerve cuff consists of 14 platinum stimulating electrodes embedded within a self-curling sheet of biocompatible insulation, exhibiting a spiral transverse cross-section. The spiral shape of the system is such that the number of stimulating electrodes which can be utilized depends on the diameter of the stimulated nerve. Nerves with a greater diameter automatically make use of more electrodes than thin ones. The development was based on results obtained by a histological examination of the peripheral nerves which were planned to be stimulated, and on models of excitation of myelinated nerve fibres. The modelling objectives were to determine the electric field that would be generated within a nerve trunk by a specific electrode. Moreover, the extent of initial excitation of the nerve fibres within the superficial region of the dog sciatic nerve elicited by a certain discrete stimulating electrode was predicted. For this purpose a calculation of activating function for six positions where the nerve fibres were supposed to lie within the longitudinally dissected sciatic nerve was performed. In two acute experiments on the sciatic nerve of the dog the objective was to characterize the effectiveness of the multielectrode system in monopolar selective stimulation of the superficial regions, innervating the gastrocnemius and tibialis anterior muscle. A selectivity preliminary tested by measuring the myoelectric activity of the gastrocnemius and tibialis anterior muscle after 2 months showed good results in both animals. PMID- 1287216 TI - An intra-oral access device. AB - Using developments from the science of electropalatography, an intra-oral access device is being developed which increases the range and sensitivity of control available to the severely physically disabled individual. The system provides the user with a consistent positional relationship between the tongue and sensor in contrast to extra-oral mounted tongue switches. The system allows the tongue to function within the oral cavity where it has maximum speed, agility and mobility and gives the user a chance to increase accuracy through practice. A major benefit of this system is its versatility. By covering the surface area of the plate with a large number of sensors, the groups of sensors that are programmed to act as switches can take any size, shape, position and number to match the user's needs and abilities. As with any developing system, a number of problems have been encountered in practical use. PMID- 1287217 TI - Effects of skin temperature on skin-electrode impedance: measurements at high direct current density. AB - Skin-electrode impedance was determined between two disposable electrodes 5 cm apart on the volar skin of the forearm in 20 patients during cooling on cardiopulmonary bypass. Measurements were made using a constant direct current pulse of 200 microseconds duration, at a current density of 25.6 mA cm-2. The mean inter-electrode resistance was 1.11 k omega, and the mean inter-electrode capacitance was 33.3 nF. In 19 patients there was no change in the inter electrode resistance or the inter-electrode capacitance with changes in skin temperature from 27.5 to 36.0 degrees C. In one patient the inter-electrode resistance increased from 1.71 k omega at 35 degrees C to 1.94 k omega at 31.0 degrees C, while the inter-electrode capacitance increased from 19.6 to 26.6 nF. We conclude that temperature effects on the impedance of the stimulus electrodes are not responsible for the observed failure of evoked electromyography during clinical monitoring of neuromuscular function. PMID- 1287218 TI - A review of cicatricial pemphigoid. PMID- 1287219 TI - Diabetes mellitus and periodontal disease: a review of the literature. PMID- 1287220 TI - Perioperative nutrition in cancer patients. AB - Cancer patients have the highest incidence of protein-calorie malnutrition seen in hospitalized patients, with significant malnutrition occurring in more than 30% of cancer patients undergoing major upper gastrointestinal procedures. Clinically significant malnutrition occurs as a result of diminished nutrient intake, increased nutrient losses, and tumor-induced derangements in host metabolism. In the absence of adequate exogenous nutrients, the body utilizes endogenous substrates to satisfy the ongoing requirements of both host and tumor for energy and protein. In those patients with malignant obstruction of the gastrointestinal tract, the tumor itself may induce diminished nutrient intake. Present day treatment modalities including gastrointestinal resection, chemotherapy, and radiotherapy compound these metabolic derangements, further increasing the risk of postoperative morbidity and death. The presence of malnutrition in cancer patients has prognostic importance. In a review of more than 3000 cancer patients, DeWys and colleagues identified significantly improved survival in those patients without weight loss compared with those had lost 6% of their body weight (Am J Med 69:491-497, 1980). Other investigators have noted increased postoperative morbidity and mortality associated with malnutrition. Early hypotheses suggested that reversal of weight loss would improve survival. The development and refinements of enteral and parenteral nutrition have provided the opportunity for studying the relationship between nutritional supplementation and postoperative prognosis. Nutrition support is therefore often instituted to improve nutritional status and thereby reduce the risks of postoperative complications. This article addresses the beneficial role of preoperative nutrition therapy in cancer patients. PMID- 1287221 TI - Overcoming difficulties in demonstrating health outcome benefits. AB - Nutrition interventions with cancer patients may produce benefits beyond those typically evaluated, such as increased appetite, food intake, and weight gain. Other benefits include enhanced mood, improved sense of well-being, and increased socialization because of an increased ability to eat in public or with family. Along with the target benefits of nutrition interventions, these "untargeted" benefits have come to be clustered under the general rubric of health-related quality of life. All medical treatments, including nutrition interventions, can be evaluated in terms of their total effect upon health-related quality of life. However, demonstrating health outcome benefits of nutrition interventions can be very difficult. This difficulty is at two levels: conceptual and practical. Conceptual difficulties can be overcome by refining and clarifying the definition and measurement of health-related quality of life. Practical difficulties are more diverse and must be tackled on a point-by-point basis, depending upon the unique characteristics of the disease being treated, the intervention being tested, and the context of the trial. This paper offers some guidelines and recommendations for overcoming many of the more commonly confronted barriers to successful demonstration of health outcome benefits from clinical nutrition trials with cancer patients. PMID- 1287222 TI - Optimal design of clinical outcome studies in nutrition and cancer: future directions. AB - Many studies have assessed the benefits of nutrition support in cancer patients. Except for studies directed at the treatment of severe malnutrition, most clinical trials have failed. Although prospective randomized controlled clinical trials (Phase III) remain the most reliable means of evaluating the efficacy of therapy, the available literature reports only results from small trials (Phase II to III), most of which appear to be contradictory and none of which conclusively answer the question being considered. To address this gap in knowledge, tools such as meta-analysis have been adapted from the field of statistics. Meta-analysis involves pooling results across several studies and provides a more precise estimate of treatment effect than can each individual study. However, clinical trials selected for meta-analysis, although broadly similar, can differ significantly in terms of therapies used and clinical populations studied. Major cancer types with differing effects on food intake and malnutrition (eg, the mechanical obstruction in head and neck cancer vs the cytokine-induced metastases associated with lung, ovarian, colon, and breast cancer) cannot be subject to the same analytic criteria. In this paper, the current state of clinical outcome trials in nutrition and cancer is examined, and the desired design for future studies is proposed. Research priorities include the conduct of Phase II clinical trials that use as outcome measures quality of life, performance status, and survival to identify optimal cancer-specific and patient-specific nutrition support. The next round of Phase III efficacy studies should establish the appropriate use of nutrition support in cancer therapy. PMID- 1287223 TI - The role of cytokines in cancer cachexia. AB - There is, at present, considerable interest in the possible role for the proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interferon-gamma in the pathogenesis of cancer cachexia. Indirect evidence for such a role is based on the observation that chronic administration of many of these cytokines, either alone or in combination, can reproduce the myriad of host responses seen in experimental and human cancer cachexia. Elevated plasma levels of tumor necrosis factor-alpha, interleukin-2, and interferon-gamma have rarely been detected in patients or experimental animals with cancer, although interleukin-6 levels appear to correlate with tumor progression in animal models. The strongest evidence for a causal role for cytokines has come from rodent studies in which tumor-bearing animals have been passively immunized with antibodies directed against individual cytokines. Several groups have shown modest but significant improvements in food intake and lean tissue retention with antibodies directed against tumor necrosis factor alpha, interleukin-1, interleukin-6, and interferon-gamma. However, there has been no consistent finding that one cytokine is universally involved in cancer cachexia in histologically distinct tumor models. One ominous finding in several tumor models has been that the endogenous production of cytokines appears to support tumor growth. Such findings raise the intriguing possibility that these cytokines, although contributors to tissue wasting and anorexia, may also serve the tumor as either direct or indirect cell growth factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287224 TI - Cytokines and their role in the pathophysiology of cancer cachexia. AB - Cancer cachexia describes a syndrome that consists of weight loss, and abnormalities in carbohydrate, protein, and lipid metabolism, which result in a state of persistent net negative energy balance. Patients suffering from cancer cachexia have a significantly shortened survival after cancer treatment. Recent experimental studies have focused on the belief that the mechanisms of cancer cachexia involve the host's production of inflammatory cytokines, which through broad physiologic actions ultimately lead to a chronic state of wasting, malnourishment, and death. Cytokines that have been thought to play a role in the pathophysiology of cachexia include tumor necrosis factor, interleukin-1, interleukin-6, interferon-gamma and differentiation factor. It has become clear that these cytokines have overlapping physiologic activities, which makes it likely that no single substance is the sole cause of cachexia in most cancer patients. Only further investigation may make it possible to more clearly define the role of cytokines in the pathophysiology of cancer cachexia. Specific strategies to reverse the cachectic effects of these substances may then be developed to ultimately improve cancer treatment. PMID- 1287225 TI - The early cancer anorexia paradigm: changes in plasma free tryptophan and feeding indexes. AB - Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10(6) methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17-18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor-associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia. PMID- 1287226 TI - Hormonal and metabolic abnormalities in the malnourished cancer patient: effects on host-tumor interaction. AB - Many common metastatic cancers are associated with marked weight loss at the time of diagnosis. Anorexia clearly plays a major role in weight loss in the cancer patient, but cannot explain all of the weight loss noted. Malnourished patients with localized cancers under metabolic ward conditions fail to gain weight when given apparently adequate calories for anabolism, thus suggesting that these patients are hypermetabolic. Increased whole body protein breakdown, increased lipolysis, and increased gluconeogenesis have been repeatedly demonstrated in malnourished cancer patients. Protein and glucose metabolism are closely linked, and both are regulated by a number of the same hormones and metabolites. For example, when increased glucose production in malnourished cancer patients is inhibited pharmacologically, protein catabolism is proportionally decreased. Studies of glucose, growth hormone, cortisol, and insulin secretion following an oral glucose load in well-nourished cancer patients are consistent with insulin resistance but no other hormonal abnormalities. Malnourished cancer patients have elevated levels of growth hormone that are further stimulated by arginine and insulin infusion. No abnormalities of thyroid function were noted in cancer patients. Current studies are underway to determine the mechanisms and effects of progestational steroids and cytokines on both food intake and intermediary lipid metabolism. PMID- 1287228 TI - Stimulation of tumor growth by nutrition support. AB - Controversy exists regarding the use of nutrition support in the cancer patient. Although nutrition support can clearly improve host nutritional status and restore immunoconfidence, the efficacy of nutrition support to reduce morbidity and mortality associated with antineoplastic therapy is questionable. A potential concern with the use of nutrition support in the tumor-bearing host is stimulation of primary tumor growth and metastasis. Numerous animal studies clearly demonstrate that oral and parenteral nutrition can significantly stimulate tumor cell proliferation and distant metastasis. Although cellular kinetic studies in humans have shown alterations after parenteral nutrition, objective measures of tumor growth, metastasis and tumor protein synthesis have not been affected by parenteral nutrition. This chapter summarizes the research and clinical work regarding the effect of nutrients on tumorigenesis, primary tumor growth, and metastasis in both animal and human tumors. PMID- 1287227 TI - Metabolic response to chemotherapy in colon cancer patients. AB - The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg vs 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute vs 2.27 +/- 0.10; p < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287229 TI - Nutrition and tumor promotion: in vivo methods for measurement of cellular proliferation and protein metabolism. AB - The notion that tumors act as "nitrogen traps" has led to the belief that nutrition support of the cancer-bearing patient can enhance tumor growth. Proponents of this theory consider the provision of energy and essential nutrients as well as the influence of hormones and growth factors as responsible for this effect. On the other hand, nutrition administration in the debilitated cancer patient may improve antitumor host defense mechanisms and reduce tumor growth. This paper reviews methodologic issues related to the study of nutrition and cancer growth with emphasis on in vivo methods for measuring tumor protein turnover and cytokinetics. Using this combined approach, we previously demonstrated that dietary fat may significantly regulate tumor growth during chronic feeding as well as with short-term intravenous nutrition support in experimental models. Although the mechanism of this effect remains unclear, we have reasoned that by altering arachidonic acid metabolism and prostaglandin synthesis, omega-3 fatty acids could change tumor protein breakdown rates and inhibit the proliferation potential of these tumors. Acknowledging alternative hypotheses, we now present cytokinetic evidence that intracellular protein degradation may regulate tumor cell proliferation. Additional studies relating dietary fat, tumor protein metabolism and tumor proliferation potential are currently in progress. We propose that the effect of nutrition administration on tumor growth is complex and involves several regulatory systems. Thus, based on available evidence, an a priori tumor-enhancing effect for nutrition support is clearly not warranted. Intracellular protein breakdown and host defense mechanisms, both of which are energy dependent, are important loci at which nutrition and tumor growth regulation could interact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287230 TI - Glutamine facilitates chemotherapy while reducing toxicity. AB - Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model. PMID- 1287231 TI - Nutrition in advanced cancer: anorexia as an outcome variable and target of therapy. AB - The endpoints used as outcome variables in clinical cancer treatment trials, including nutrition intervention studies, should contain items that are meaningful to the patient. Variables to consider are appetite, food intake, physical performance, psychological and social functioning, response to cancer therapies, survival time, nutrition status, associated morbidity, and costs. Ideally, the design and conduct of nutrition trials should be carried out by a multidisciplinary team comprising medical oncologists, physician specialists in nutrition, dietitians, and social scientists. Anorexia has not been a focus of nutrition support trials in the past partly because of the lack of effective strategies to reverse it. Anorexia is one important cause of cancer starvation, and it also causes patient discomfort. This paper describes outcome variables that include patient derived subjective factors such as anorexia, and outlines new strategies to reverse anorexia. Pharmacologic strategies tested to reverse anorexia include corticosteroids, anabolic steroids, cyproheptadine, hydrazine sulfate, cannabinoids, and megestrol acetate. Of these, only the latter has been consistently well tolerated and effective, with significant improvements in appetite and food intake demonstrated in large-scale, randomized, controlled trials involving more than 600 cancer patients. Dose-response studies have demonstrated increasing efficacy with increasing doses of megestrol acetate from 160 to 800 mg/day. Doses in excess of 800 mg/day are not currently recommended. The mechanisms of action of megestrol acetate involve both behavioral and metabolic effects, and its impact on energy expenditure, appetite, body composition, endocrine function, and lipid metabolism is the subject of ongoing research.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287233 TI - [Chronic fatigue syndrome: the present concept and historical perspective]. PMID- 1287232 TI - Home parenteral nutrition in patients with a cancer diagnosis. AB - The clinical outcome for 1362 patients with active cancer managed on home parenteral nutrition (HPN) is compared with that of 122 patients with radiation enteritis ("cured" cancer) and 416 patients with Crohn's disease. This longitudinal clinical information was reported to the North American Home Parenteral and Enteral Nutrition Registry (Oley Foundation/A.S.P.E.N. joint project) between 1985 and 1989. The data shows that the number of active cancer patients on this therapy is increasing 13% per year. The annual survival rate is 25% for patients with active cancer, as compared with 88% for patients with radiation enteritis and 95% for patients with Crohn's disease. Although 50% of all active cancer patients starting HPN are dead within 6 to 9 months, the prognosis is somewhat better in children, and 20% of these active cancer patients appear to do well, returning to full oral nutrition and experiencing complete rehabilitation. These are presumed to be patients with a potentially curable cancer requiring super-aggressive treatment, which causes temporary severe gastrointestinal dysfunction. Adult active cancer patients have the same rehospitalization rate for HPN complications (once per year) as radiation enteritis and Crohn's disease patients. However, their rehospitalization rate for non-HPN complications is four times higher. This article reviews the factors that may explain the growth of HPN in active cancer patients and discusses some of the unanswered clinical questions that urgently need to be addressed to more effectively determine the appropriateness or inappropriateness of HPN management in the active cancer setting. PMID- 1287234 TI - [Chronic fatigue syndrome--symptoms, signs, laboratory tests, and prognosis]. AB - Chronic fatigue syndrome (CFS) is an undefined clinical problem and is perceived as a complex of multiple symptomatology with an unexplained persistent fatigue. Major symptoms include fatigue lasting for more than 6 months, low-grade fever, moderate lymphadenopathy, muscle and joint pain, and various psychological presentations. Since no specific laboratory tests are available, clinical diagnosis demands that known causes of chronic fatigue should be excluded. The pathogenesis is at present unknown, but it is suspected that CFS is a physical and psychological condition associated with some unrecognized infectious agent. Further study is needed to clarify the precise pathophysiology of this newly recognized entity. PMID- 1287235 TI - [Definition of the chronic fatigue syndrome and its issues]. AB - This article reviewed Definition of CFS proposed by CDC 1988. There are several issues in Definition for CFS of CDC. It is presented that other chronic clinical conditions have been satisfactorily excluded, including preexisting psychiatric diseases in (2) of major criteria. However, fibromyalgia can not be excluded from the fifth symptom of minor criteria, myalgia, and also depression from the ninth symptom. It is practically difficult to define impairment of average daily activity below 50% of the patient's premorbid activity level for a period of at least 6 months, as shown in (1) of major criteria, and it is not adapted for a first visit patient. Definition for CFS of CDC has been discussed on EBV infection, but not written on postviral fatigue syndrome and myalgic encephalomyelitis. Especially whether epidemic type of CFS is present or not was not discussed. Diagnostic criteria of CFS is necessary for clinical practice. PMID- 1287236 TI - [Diagnostic criteria for chronic fatigue syndrome by the CFS Study Group in Japan]. AB - Much interest recently has been given to chronic fatigue syndrome (CFS) in Japan as other countries. The CFS Study Group sponsored by the Ministry of Health and Welfare has been developed since April 1991, A diagnostic criteria for CFS was newly proposed by this group. The criteria is substantially based upon the working case definition, which was made by Holmes and colleagues in 1988. There are some modification from CDC working case definition; the criteria of probable cases of CFS was defined, and postinfectious CFS was also given. PMID- 1287237 TI - [Chronic fatigue syndrome in school children]. AB - Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing debilitating fatigue for at least 6 months without any apparent medical diagnosis that would explain the clinical presentation. Although, most of the reported patients are over age 30, CFS also affects school children. To better understand CFS, the network of the central nervous-endocrine-immune systems should be considered, and one must be careful to distinct CFS from school absenteeism and other psychosomatic disorders often seen among them. PMID- 1287238 TI - [Chronic fatigue immune dysfunction syndrome]. AB - Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks. Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems. Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS. PMID- 1287239 TI - [Neuro-psychiatric aspects of chronic fatigue syndrome]. AB - Chronic fatigue syndrome (CFS) is easily differentiated from various neurological organic disorders by conventional clinical examinations. The most important disease for distinguishment from CFS is fibromyalgia syndrome, in which the prominent and cardinal feature is a deprivation of stage 4 slow wave sleep. Experimentally, the sleep disturbance in controls can induce general myalgia, muscle tender points, severe fatigue and stiffness on awakening. The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS. Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity. PMID- 1287240 TI - [Overview of our patients with chronic fatigue syndrome (CFS) from the pathoetiological aspects]. AB - We interviewed 285 patients who visited our department claiming with a complaint of chronic fatigue syndrome (CFS) and subsequently diagnosed 55 as having CFS, according to the criteria for CFS of the centers for disease control (CDC). We measured various virus antibody titers, 2-5, adenylate synthetase levels in the serum lymphocyte subset in blood, employing a double staining technique with monoclonal antibodies. In this paper, we pathoetiology of CFS, based on our findings and other researchers' is discussed. PMID- 1287241 TI - [Chronic fatigue syndrome--51 cases in the Jikei University School of Medicine]. AB - Between April 1991 and August 1992, we diagnosed 51 cases of CFS who met definition of CFS designated by CDC, 1988. They are 41 female and 11 male, and 78% are women. At first visit, their ages are ranged from 16 to 64 years old, and approximately 45% is 20 to 30 years old. In periods of illness from onset, 39.2% of the patients are in period of 6 month to 1 year, 19.6% within 2 years, and 15.6% within 3 years, respectively. The sufferer who have symptoms of CFS over 10 years long are in 6 cases. Most of patients have already been examined by many other clinics and hospitals. They have been told as no abnormal medical condition, or often as neurosis, depressive state and autonomous imbalance etc. Interesting things are trigger of CFS. 77.5% of patients have onset of flu-like symptom, including 5 cases of acute infectious mononucleosis. In many female patients, symptoms of CFS begun after hand work in addition to psychological factors. Specific laboratory results are not shown in CBC, urinalysis, biochemical studies and inflammatory marhers. 6 cases hare positive Rheumatoid factor and positive ANF are shown in 16 cases (31.3%). Specific patterns of anti EBV antibodies are not shown. Lymphocyte subsets used by monoclonal antibodies are not specific. At the present, prognosis is good and 56.8% of CFS patients are generally improved. For severe cases, NSAID, Sulpiride, Amitryptiline and minor tranquilizer are used. PMID- 1287242 TI - [Therapy of chronic fatigue syndrome]. AB - Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a number of clinical trials have been performed in CFS patients, there is currently no established therapy for CFS. Treatment with acyclovir of CFS patients is ineffective. Intravenous immunoglobulin therapy appears to be effective, though the results are controversial. Antidepressants might help the associated depression and anxiety but not other symptoms. Trials with magnesium have improved the well-being of patients. Restoration of NK activity by biological response modifiers, such as sizofirann, resulted in restoration of NK cell activity and recovery from CFS. Taken together, immunological abnormalities may be involved in CFS, and its restoration may produce clinical benefit in CFS. PMID- 1287243 TI - [Irritable bowel syndrome--criteria, sub-classification, etiology]. AB - The irritable bowel syndrome (IBS) is a very common condition in gastroenterology clinics, but yet it is one of the pooly understood. A international working team in Rome, 1988, proposed that IBS is a functional intestinal disorder with chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. IBS was sub-classified into 3 groups; abdominal pain as the prominent feature with diarrhea, with constipation, with both while painless diarrhea and simple constipation without pain were excluded from IBS. There is a lot of data suggesting that IBS has a gut dysmotility, which is influenced by many stimuli (food, hormone, drug, menses, mechanical dilatation), including psychological stress. Moreover, currently available evidences implicate that IBS is a more generalized disorder of smooth muscle function not only in the intestine but also outside of the intestine. PMID- 1287244 TI - [Functional abnormality of the digestive tract and the gall bladder in irritable bowel syndrome]. AB - Functional abnormalities of the digestive tract and the gallbladder in irritable bowel syndrome (IBS) are described in this review. In addition to colonic abnormalities, disordered oesophageal motility, abnormal gastric emptying, abnormalities in small intestinal motility and abnormal gall bladder function have been demonstrated in IBS. Urodynamic abnormalities and bronchial hyperreactivity also have been reported in patients with IBS. Such extensive involvement of the organs suggests that IBS can be a generalized abnormality of the smooth muscle of even the whole body as well as the whole digestive tract. Further detailed investigation is needed to clarify this possibility. PMID- 1287245 TI - [Role of gut hormones in irritable bowel syndrome]. AB - In irritable bowel syndrome (IBS), motility disturbances occur from the upper gastrointestinal tract to the distal colon, where regulatory peptides have a wide spread distribution. Studies on basal and postprandial plasma levels of different gut hormones show that VIP, CCK, and motilin may be closely related to the symptoms including abdominal pain, diarrhea and constipation. In addition, peptide YY and NPY have effects on absorption in the intestine, and some opioid peptides exert actions on colonic motility in IBS patients. Recent studies revealed that gall bladder in IBS has an abnormal sensitivity to CCK-8, indicating that IBS patients has an generalized abnormality of the smooth muscle of the digestive tract. Gut hormones, which act as hormones, neurotransmitters and neuromodulators depending on their releasing site, may therefore play an important role in IBS patients. PMID- 1287246 TI - [Concept and differential diagnosis of irritable bowel syndrome]. AB - The exact etiology of irritable bowel syndrome (IBS) is unknown. IBS is probably one of the commonest gastrointestinal disorders, but it has proved to be one of the most difficult conditions to diagnose. A proportion of patients give a strong history of stress-related or stress-evoked symptoms. In the past there has been a paucity of studies of this disorder because of difficulties in patient selection, choice of appropriate marker to be tested and the correlation of findings with the clinical presentation. A clear and precise definition of IBS is of most importance in the understanding of psychopathophysiological markers in this disorders. PMID- 1287247 TI - [The relation between irritable bowel syndrome and a major depression]. AB - It has been demonstrated that physical or psychological stress induces dysfunction of bowel movement and intestinal transit in rodents and human. There have been several reports concerning the psychiatric factors involved in the onset and clinical course of irritable bowel syndrome (IBS). We investigated patients with IBS who had been markedly disturbed in their daily life, and it was concluded that the most important psychiatric factor related to the onset and the clinical course of severely impaired IBS is a major depression, fulfilling the criteria of the DSM-III-R. Especially, in diarrhea predominant type of IBS, a major depression was considered to be strongly involved in the onset and the clinical course of IBS. Most of IBS patients with a major depression can be effectively treated with antidepressants and brief psychotherapy. Concerning treatment, the psychological background should be carefully considered. PMID- 1287248 TI - [Irritable bowel syndrome in children]. AB - The irritable bowel syndrome (IBS) is characterized by alteration in bowel habits (i.e., constipation and/or diarrhea) and abdominal pain, and is most common gastrointestinal disorder in adults. The recurrent abdominal pain (RAP) in children is similar to IBS in adults except bowel habits, but there is no settled conception of IBS in children. In our department, diagnosis of pediatric IBS will be made if the child has; #1 functional gastrointestinal disorders without organic diseases, #2 abdominal pain and other gastrointestinal symptoms continuing more than 3 weeks, #3 psychogenic background factors. We experienced 63 cases of IBS (23.5% in all 268 cases) from April 1990 to March 1992 at our pediatric digestive outpatient clinic. They ranged from 4 to 15 years old and about 60% of them were elder than 13 years old. Psychogenic factors were usually related to environment of school life and home. Careful history taking and routine examination were most important for the diagnostic approach. Management of this disease included counseling and drug therapy. Almost all cases reached much better condition 1 to 6 weeks after the therapy started. The combination therapy with psychologist was required in a few cases. PMID- 1287249 TI - [Therapy by Japanese Oriental medicine (kampo) in irritable bowel syndrome]. AB - Guideline for the treatment of irritable bowel syndrome by Japanese Oriental Medicine (Kampo) is summarized. It is very important to notice that Kampo prescription will show its best efficacy if it is adjusted for the conditions of a patient. To diagnose ill conditions for the patient is called the process of "Sho" clarification. Sho is the ultimate diagnosis, which is the term given to summarization of diagnostic process for a patient. Conceptual criteria used for making up Sho are "Yin/Yang", "Kyo/Jitsu", and "Hot/Cold". A Kampo formula has its own position regarding these concepts. We interpret about these concepts and formulae. Another important method for making Sho diagnosis is abdominal diagnosis, which is relatively easy to learn. Certain signs in abdominal diagnosis correspond to certain formula. We explain some methods in abdominal diagnosis and the related formulae. We also comment on construction process and features of Kampo prescription. PMID- 1287250 TI - [Psychosomatic treatment of irritable bowel syndrome]. AB - Irritable bowel syndrome (IBS) may be defined as a psychosomatic disease. Most primary care physicians do not want to undertake psychosomatic treatment, but may find it necessary in refractory patients. Brief psychosomatic treatments, providing patients with betterways to cope with stress, reduce the symptoms. The literature on the psychosomatic treatment for IBS is summarized. Supportive therapy and autogenic training that produce relaxation response appear to be effective. Other special psychological therapies that require specialized training, such as hypnosis, biofeedback, cognitive therapy, transactional analysis may be used for IBS but adequately controlled trials are lacking. It is certain that psychosomatic treatment take part in the management of IBS. Additional studies are needed to verify the effectiveness of these treatment for IBS. PMID- 1287251 TI - [Coagulase-negative staphylococcal infections]. AB - Coagulase-negative staphylococci are resident flora of the human being and not harmful for ordinary patients. However they cause serious infection for the compromised host, especially the patients with prosthetic valve, prosthetic joint, cerebrospinal fluid shunt, or intravascular catheter. Recent progress of medicine has resulted in the increase of compromised hosts. So, coagulase negative staphylococci became one of the significant pathogens of hospital infections. Moreover, some hospital strains of coagulase-negative staphylococci demonstrate the resistance against most of the antibiotics recently. To prevent the hospital infection caused by those strains, the contamination control of the prosthetic insert is essential. When once the infection is caused on the prosthetic insert, they have to be removed in most cases. PMID- 1287252 TI - [Panic disorder]. AB - Panic episodes were described as a distinct form of anxiety by Freud almost 100 years ago, and the recent publication of the Diagnostic and Statistical Manual of Mental Disorders, third edition (D.S.M.-III), has provided the basis for the separate diagnostic entity of panic disorder. In this study, we showed the historical review of research and the result of our clinical study of panic disorder in 7 patients. The following results were obtained: 1) Abnormal DSTs were observed in only two of 5 patients. 2) Five of 6 patients showed high concentration of adrenaline and noradrenaline in urine. 3) Anxiety was provoked by caffeine in two of 5 patients. 4) Depression of T-wave was shown in three of 5 patients with orthostatic E.C.G. 5) Sinus tachycardia was gained in one of 3 patients with Holter E.C.G. 6) Abnormal respiratory functions were observed in all two patients with Treadmill. 7) Only one small heart was observed on a chest radiograph. 8) Panic attacks were provoked by sodium lactate infusion in four of 7 patients. PMID- 1287253 TI - [Molecular biology of glycoconjugates in eukaryotic cells]. AB - Glycoconjugates, such as glycoproteins and glycolipids, are one of the macromolecules composing a living body. Biological roles of carbohydrate moieties in glycoconjugates have recently drawn great attention. Sugar chains of glycoconjugates comprise an enormous diversity of structures which are known to be expressed in a cell specific manner and are regulated with stage specificity during embryogenesis and cell-differentiation. It is generally accepted that genetic expression and regulation of glycosyltransferases which are present in Golgi apparatus determines the structures of sugar chains. For these several years, a number of successes of cDNA cloning of glycosyltransferases have been reported. Recent progress and accumulated molecular cloning evidences of glycosyltransferases are reviewed and future advance using cloned genes as useful tools for glycobiology and glycotechnology is discussed. PMID- 1287254 TI - [Hybridoma Data Bank (HDB)]. AB - A Hybridoma Data Bank (HDB) has been developed with the collaboration of ATCC (USA), Cerdic (Europe) and RIKEN (Japan). The database holds more than 23000 records of the monoclonal antibodies. HDB is designed to meet diverse research requirements. HDB describes the development, isotype, specificity, applications, availability and literature citations for an individual monoclonal antibody. The World Data Center (WDC) at RIKEN in Japan is currently giving users' access to HDB on INTERNET, packet switching system and telephone line. The procedures for access to WDC and the interactive information retrieval system in WDC are introduced. The extraction of HDB data to create the visual table, showing reactivity patterns of monoclonal antibodies, are also shown, as an example of intelligent usage of HDB. PMID- 1287255 TI - [Structures and functions of adhesion molecules--involvement of adhesion molecules in the pathogenesis]. AB - Previous studies have revealed that adhesion molecules are involved in immune responses, such as the interaction between T cells and antigen presenting cells. Recent investigations demonstrated that one of these molecules, integrins, which was concerned with cell-cell adhesion and cell-extracellular matrix proteins, was prominently expressed on lymphocytes and neutrophils in inflammatory diseases. In addition, administration of monoclonal antibodies against integrins in vivo abrogated the inflammatory responses completely in rats. These findings suggest that adhesion molecules are involved in not only immune responses but also in the pathogenesis of inflammatory diseases. As shown here, integrins also play an important role in the metastasis of small cell lung cancers. PMID- 1287256 TI - [Imported parasitic diseases--recent epidemiology and progress in the chemotherapy]. AB - Imported parasitic diseases have been increasingly important in basic and clinical medicine in developed countries, as the number of travellers in developing countries, where numerous kinds of parasitic diseases are highly endemic, have been increasing. Recent epidemiologic investigation demonstrated that malaria, amebiasis, trypanosomiasis, leishmaniasis and cysticercosis seemed important as judged from the number of infected individuals, primarily Japanese travellers. Although these parasitic diseases pose some serious medical problems, establishment of the effective chemotherapeutic strategy is of urgent significance. In this respect, activities of the Research Group of Development of Chemotherapeutic Agents against Tropical Parasitic Diseases supported by the Japanese Ministry of Health and Welfare appear to be important to keep appropriate drugs in Japan. PMID- 1287257 TI - [Recent trends in estimating energy expenditures in Japan]. AB - Estimating energy expenditures for daily activities has become an important issue in the promotion of individual health. From this point of view, the variety of estimation methods and their characteristics applied in many countries were surveyed. Then the essential bases used to estimate energy expenditures with the relative metabolic rate (RMR) method and the active energy expenditure rate (Ea) method, which were originally developed and used in Japan, were substituted for daily activities recorded by means of time study, and illustrated. Subsequently, a newly introduced method based on heart rate was explained with its variations and problems followed by practical reports on some populations in Japan. Methods using questionnaires or other devices were also described. PMID- 1287258 TI - [Changes of nutritional factors related to regional differences in the mortality of cardiovascular disease between 1966 and 1985 in Japan]. AB - Cardiovascular disease has been the leading cause of death since 1946 in Japan. In this paper, the relationship between mortality and nutritional factors was analyzed by 12 different regions in Japan during the period 1966-1985. Data in the Reports of the National Nutritional Survey in Japan were used as the nutritional factors, and calculation was made of age-adjusted mortality from ischemic heart disease (IHD), cerebral hemorrhage (CH) and cerebral infarction (CI). The results obtained were as follows: 1. Correlation coefficients were calculated based on the average value of 20 years in each 12 different regions. Correlation coefficients between the mortality from IHD and intake of total fat and n3-polyunsaturated fatty acids were positively significant for both sexes. Between the mortality from CH and vegetable protein and salt, they were positively significant (p < 0.01) while cholesterol was negatively significant (p < 0.01). Between the mortality from CI and vegetable protein, salt and carbohydrate, they were positively significant (p < 0.01). 2. Correlation coefficients between slopes of CH and slopes of nutrients intakes, indicated cholesterol to be negatively significant (p < 0.05) for women from 1966-1970, and salt to be positively significant for men (p < 0.01) and women (p < 0.05) from 1974-1985. In the period 1966-1970, the correlation coefficient between slopes of IHD and those of Keys' factor was positively significant (p < 0.05) for women. 3. To clarify changes in the relationship between mortality and nutrients, correlation coefficients were calculated each year from 1966 to 1985. Significant positive correlation coefficients for IHD were found with animal protein and saturated fat starting from about 1975. Salt was associated with IHD in the 1960s but not following 1970. Those of nutrients for CH and CI did not change markedly during 18 years. 4. Multiple regression analysis with intake of salt and Keys' factor indicated that the influence of salt on cardiovascular disease to decreased and that that of low serum cholesterol on CH declined. Multiple correlation coefficients with salt and Keys' factor decreased for IHD (men) and CH (women). PMID- 1287259 TI - [Instrumentation of birth weight in obstetric facilities]. AB - An investigation on measurement of birth weight in facilities was made in the northern part of Fukuoka Prefecture from March 1989 to January 1991. The purpose of the investigation was to clarify the reliability of birth weight data in obstetric facilities. The author interviewed the manager of each facility. The data of 112 cases were analyzed. The following results were obtained: 1) Nurses and midwives measured birth weights in many facilities, but doctors rarely did. Birth weights were obtained within an hour after birth in almost all facilities. Tare and zero-adjustment were frequently checked in many facilities, but horizontal-adjustment was not checked in about a half of the facilities. 2) The types of scales were digital scales (48.2%), dial scales (31.3%), table-top platform scales (10.7%) and bathroom scales (9.8%). It was estimated that 70.6% of the all birth weights in these facilities were obtained with digital scales. The renewals of scales in the past 5 years has resulted in the widespread use of digital scales in facilities. 3) The accuracy and precision of each scale were examined with weights of 3000g. Digital scales were superior to the other types of scales in both accuracy and precision. The legal periodical inspection for scales improved accuracy. Procedures for measuring birth weight are not generalized among and within facilities. Digital scales have many merits for handling and reading. The spread of digital scales in facilities may decrease the degree of many kinds of errors in measurement, especially rounding errors, and improve the reliability of the data in the area. PMID- 1287260 TI - [Work history, health conditions and hearing loss of Ishigaki fishermen]. AB - Based on our previous health survey among Ishigaki fishermen in 1979, this study aimed at clarifying the relations of their work histories to physical characteristics, physiological functions, blood conditions and hearing levels. Medical examination was conducted in 1987 on 118 fishermen inclusive of 33 followed-up fishermen, and in 1989 noise-level and noise-induced temporary threshold shift of hearing was measured for different fishing methods. The results were as follows; 1) Fishing history was not specifically associated with any physical characteristics. 2) High HDL cholesterol, which was observed among divers using diving apparatus, was considered to be a survival effect for divers, since HDL cholesterol is amplified by intensive muscle work. 3) Abnormalities of ECG except for a high R wave were notably observed among the divers, who once changed from unassisted diving to diving with apparatus and then to fishing lines. The main reason for switching jobs was claimed to be caisson disease, and it was suggested that diving with apparatus was related to a high risk of health hazards in the central nervous system and/or respiro-circulatory system. 4) Acoustic acuity greatly declined with aging, and which was commonly observed in groups with different work histories. By way of explanation, exposure to ship engine sounds during daily travelling was the most likely cause. It was also revealed that several hours' exposure to the engine sounds was needed to detect a temporary threshold shift of hearing before and after work. PMID- 1287261 TI - [A study of the humoral immunity of mice injected with beryllium chloride]. AB - We studied changes of humoral immunity, such as complement pathway activity, C3 contents and contents of immunoglobulin, in mice injected subcutaneously with BeCl2 or CuCl2 once a week for 12 weeks. Mean body weights of JCL: ICR female mice were approximately 30g in control mice (control group; n = 7), in mice injected with Be (Be group; n = 8) and in mice injected with Cu (Cu group; n = 8). Values of classical complement pathway activity (CH50) were 18.8 +/- 1.4 U per ml, 15.3 +/- 1.8 U per ml and 16.7 +/- 1.3 U per ml in the control group, Be group and Cu group, respectively. The CH50 values of Be and Cu groups were significantly lower than that of the control group (P < 0.01). In contrast, values of alternative complement pathway activity (ACH50) and contents of C3 were almost constant in the three groups. The immunoglobulin content in the Be group tended to increase. The activity of alanine aminotransferase in the Be group was markedly higher than that in the control group (P < 0.05), and the aspartate aminotransferase activity was also high. The CH50 value of mice injected with a small amount of Be once a week over a 12-week period decreased markedly, although either the ACH50 value or C3 content was the same as in the control group. The immunoglobulin content somewhat increased in the Be group. These results suggest the possibility that immune complex is induced by Be. PMID- 1287262 TI - [Conditions for low-intensity voluntary wheel running in rats and its chronic effects on health indexes]. AB - Studies were undertaken to evaluate the fundamental conditions for a low intensity voluntary wheel running model in rats and its chronic effects on health indexes. Male Fischer rats (SPF) 5 weeks of age were housed in individual sedentary conditions or in individual wheel-cage units which allowed free access to voluntary wheel running for 8 months. Voluntary running averaged 640 +/- 198 m/day, reached a peak (965m) at the 2nd month and waned over time, reaching a plateau after the 6th month (about 400-500m). Exercising rats consumed more food (+23%), but exhibited decreased body weight gains (-9%), suggesting a remarkable lowering of fat. A lowering effect on resting blood pressure (-5%) was also recognized. In addition, preventive effects on oxygen toxicity and effective bactericidal activity of neutrophils and pulmonary alveolar macrophages (PAM) were suggested. Although the amount of exercise in this study was the smallest of the other preceding ones conducted with a voluntary wheel running model, many potential health benefits were recognized. Such health promoting and protective effects by low-intensity voluntary exercise and the harmfulness of forced exercise in rats have been reported in researches on cancer, lowering fat and hypertension. Therefore it is important to set up conditions for low-intensity voluntary running. It was also demonstrated by this study that strictly controlled environmental conditions, such as room temperature and humidity, a 12 hr light-dark cycle and prevention of infection and psychological stress to rats, as well as using male rats, which are more inactive, were important factors to establish this model. PMID- 1287263 TI - [Instantaneous changes in sleep stage due to the sound of a passing truck]. AB - The instantaneous effect of the sound of a passing truck on sleep of five male students, 23 to 25 years of age, was assessed. The peak levels of noise were adjusted to 55, 60, and 65 dB (A) with intervals of 18 and 13 minutes, and a frequency of one per hour. Background noise in the experimental room was Leq 42 dB (A). The sleep stage of each epoch was visually judged based on the criteria of Rechtschaffen & Kales. Data for pre-exposure epochs of sleep stage 2 and rapid eye movement (REM) were collected and 18 epochs, including two under noise exposure, were evaluated. Three sets of polygraphic data were sampled as controls from 10 minutes after 65 dB (A) exposure to the next exposure. Compared with the control, the percentage of stage 2 to shallower stages (stage 1, waking, or movement time (MT)) was significantly increased by exposure to 55, 60, and 65 dB (A). The change lasted for one minute with exposure to 55 dB (A), and 2 to 3 minutes with 60 and 65 dB (A). A decrease in the percentage of stage 2 to deeper stages was observed at 2 to 4 minutes after exposure to 60 and 65 dB (A). The percentage of stage 2 to MT increased at 60 and 65 dB (A). The percentage of stage REM to other stages increased with the exposure to 60 or 65 dB (A) within 4 minutes. The threshold of instantaneous change of stage 2 to shallower stages due to the sound of a passing truck was at the peak level at less than 55 dB (A), and that of stage REM to other stages at 55 to 60 dB (A). PMID- 1287264 TI - Acute effects of alcohol on cognitive function and central nervous system assessed by auditory event-related potentials. AB - To clarify which sites of the central nervous system are influenced by acute administration of alcohol at an early stage, auditory event-related potentials (ERP) using a target-selection paradigm were measured in 13 healthy volunteers. In the recorded waveforms of ERPs, the N100, P165, N200 and P300 latencies for the target tone and the N100 and P200 latencies for the non-target tone were determined in each subject before and 1- and 2-hr after ingestion of 200 ml of alcohol (containing 25% ethanol) or of 200 ml of water, for a total of six times on two different days. The P300 latency was significantly prolonged at 1- and 2 hr after alcohol ingestion; and, the N200 latency was significantly prolonged at 2-hr after alcohol ingestion. The 2-hr alteration in the P300 latency after alcohol ingestion was positively correlated with the ethanol dose per body weight. These data suggest that ethanol, in proportion to its dose, affects cognitive function estimated by the P300 latency earlier than other lower central nervous system functions. Evaluating subclinical effects on central nervous function, using the ERPs, of environmental neurotoxins such as organic solvents, researchers should pay particular attention not only to the degree of the drinking habit but also to the interval between the measurement and alcohol intake. PMID- 1287265 TI - Injury to cultured human vascular endothelial cells by copper (CuSO4). AB - The effect of copper sulfate (CuSO4) on cultured human vascular endothelial (HVE) cells and cultured human fibroblasts (HAIN-55) was investigated. HVE cells were collected from umbilical veins by enzymatic digestion with collagenase. The viability, subsequent growth and DNA synthesis of both cell types were inhibited concentration-dependently by the addition of copper. The cytotoxic effect of copper on the morphology of these cells was also concentration-dependent. However, the cytotoxic effect of copper on the viability, subsequent growth and DNA synthesis was greater in HVE cells than in HAIN-55 cells. These results suggest that HVE cells are more susceptible to concentration-dependent copper cytotoxicity than HAIN-55 cells are, and that copper could induce vascular endothelial injury, which may be involved in the pathogenesis of cardiovascular disease. PMID- 1287266 TI - Protective activity of silipide on liver damage in rodents. AB - The activity of silipide, a silybin-phosphatidylcholine complex (IdB 1016), was tested in different models of liver damage in rodents. After oral administration, silipide exhibited a significant and dose-related protective effect against the hepatotoxicity induced by CCl4, praseodymium, ethanol and galactosamine. The ED50 values for inhibition of the rise in ASAT and ALAT levels caused by CCl4 and praseodymium and for antagonism of the increase in liver triglycerides caused by ethanol ranged from 93 to 156 mg/kg (as silybin). At a dose of 400 mg/kg (as silybin), silipide was also active in protecting against paracetamol-induced hepatotoxicity. Silybin and phosphatidylcholine at doses equivalent to those contained in the active doses of silipide failed to show any significant protective activity in these models. The liver protective effect of silipide is probably related to its antioxidant activities and to a stimulating effect on the hepatic synthesis of RNA and proteins. PMID- 1287267 TI - Daily variation in the effects of furosemide in rats. AB - Daily variation in the effects of furosemide, a loop diuretic agent, was examined in Wistar rats maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Furosemide (30 mg/kg) was given orally at 12 p.m., 4 a.m., 8 a.m., 12 a.m., 4 p.m. or 8 p.m. Urine was collected for 8 hr after furosemide administration, and urinary excretions of sodium and furosemide were determined. There were significant daily variations in the urine volume and urinary excretions of sodium and furosemide with a peak at 8 a.m. and a trough at 12 p.m. Significant correlations were observed between the urinary amount of furosemide and its diuretic effects (urine volume and urinary sodium excretion). These results suggest that the diuretic effects of furosemide show daily variations which are, at least in part, caused by the daily variation in the urinary excretion of furosemide. PMID- 1287268 TI - Effect of DS-4574, a novel peptidoleukotriene antagonist with mast cell stabilizing action, on acute gastric lesions and gastric secretion in rats. AB - DS-4574 is a peptidoleukotriene antagonist with mast cell stabilizing activity. In the present study, we studied the effects of this compound on gastric secretion and various acute gastric lesions in rats. Intraduodenal administration of DS-4574 at doses of 5 to 10 mg/kg significantly and dose-dependently inhibited gastric acid secretion in pylorus-ligated rats, but a further increase in the dose up to 50 mg/kg did not cause any further inhibition. Shay ulceration in response to pylorus ligation was dose-dependently prevented by DS-4574 (10-25 mg/kg, i.d.). Water-immersion restraint stress- and aspirin-induced gastric ulcers were also significantly prevented in a dose-related manner by oral pretreatment with DS-4574 (10-50 mg/kg). The lower doses of DS-4574 (1-10 mg/kg, p.o.) significantly and dose-dependently protected the gastric mucosa against the necrotizing action of either absolute ethanol or concentrated hydrochloric acid, indicating that this compound possesses a potent gastroprotective activity. These antiulcer and gastric protective effects of DS-4574 were more potent than those of cimetidine used as a reference drug. These findings suggest that DS-4574 is useful for peptic ulcer therapy, as well as for the therapy of various allergic diseases, including asthma. PMID- 1287269 TI - Regional vascular responses to thromboxane A2 analogue and their blockade with vapiprost, a selective thromboxane receptor blocking drug, in anesthetized dogs. AB - Regional vascular responses to the thromboxane A2 analogue U46619 and effects of the selective thromboxane receptor blocking drug vapiprost on these responses were examined in anesthetized dogs. Hemodynamic responses to U46619 (0.5 micrograms/kg into the left atrium), norepinephrine (NE, 0.3 microgram/kg, i.v.) and angiotensin II (AII, 30 or 60 ng/kg, i.v.) were periodically tested before and after administration of vapiprost (10, 30 or 100 micrograms/kg, i.v.) or its vehicle. In the absence of vapiprost, U46619 increased total peripheral (TPR), vertebral (VR), coronary (CR) and renal (RR) vascular resistance by 60.1 +/- 4.7%, 33.6 +/- 4.9%, 15.3 +/- 1.3% and 120.8 +/- 17.4%, respectively, indicating that vasoconstrictor responses to U46619 were most prominent in the renal vascular bed as compared to those in the vertebral or coronary vasculatures. Vapiprost as well as the vehicle did not affect the base-line hemodynamics. However, vapiprost apparently inhibited the U46619-induced vasoconstriction in all measured vascular beds in a dose-related manner without attenuating vasoconstrictor responses to NE compared to the inhibitions of VR and CR. These results demonstrate that there was a regional difference both in the vasoconstrictor responses to U46619 and in the blocking effects of vapiprost, and indicate that vapiprost is a potent and selective antagonist for thromboxane receptors in vivo. PMID- 1287270 TI - Fluorescent probe-labeled lipid microsphere uptake by human endothelial cells: a flow cytometric study. AB - Lipid microspheres have been used as carriers of drugs such as prostaglandin E1 (lipo-PGE1) and corticosteroid (liposteroid). Lipo-PGE1 is used for the treatment of chronic arterial occlusive diseases because its activity is far greater than that of free PGE1 in vivo. To verify the fact that the drug carriers, lipid microspheres, are preferentially taken up by endothelial cells, we labeled lipid microspheres with a fluorescent probe, DiI (DiI-LM), and observed them in some in vitro models. Stoichiometric fluorescence was obtainable, and the fluorescence was stable between pH 3.3 and pH 8.9. Human umbilical vein endothelial cells and cells of a human endothelial cell line, ECV304, showed increased uptake of DiI LM, 81% and 61%, respectively. In contrast, uptakes were less than 7% in human skin fibroblasts, 3T3 cells, and human neutrophils. Prominent perinuclear fluorescence was also observed in endothelial cells by fluorescence microscopy. DiI-LM and flow cytometric analysis will be useful for studies to elucidate the precise mechanism of the selective accumulation of lipid microspheres by cells in blood vessel walls. PMID- 1287271 TI - Involvement of nitric oxide in endothelium-dependent, phasic relaxation caused by histamine in monkey cerebral arteries. AB - Monkey cerebral artery strips partially contracted with prostaglandin F2 alpha responded to histamine with biphasic patterns of relaxation. The delayed and sustained relaxation was suppressed by cimetidine, whereas the phasic response was abolished by treatment with chlorpheniramine and NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The inhibition by L-NA was reversed by L arginine. D-NA was without effect. Endothelium denudation abolished the phasic relaxation. We hypothesized that endothelium-dependent, phasic relaxations caused by histamine are mediated by NO that is released by H1-receptor stimulation, whereas the sustained relaxation is associated with the activation of H2 receptors in the smooth muscle of monkey cerebral arteries. PMID- 1287272 TI - Heparin inhibits the progression phase of subcultured endothelial cell proliferation in rat aorta. AB - The anti-proliferative effects of heparin on subcultured endothelial cells (EC) of rat aorta were investigated to determine whether heparin inhibits the competence phase or the progression phase in the cell cycle using the starting time and the rate of proliferation. Fetal bovine serum (FBS)-stimulated EC proliferation increased to 1.5-times in cell number, but decreased to 0.5-times in 3H-thymidine incorporation, compared with the proliferation of rat primary cultured smooth muscle cells (SMC). The FBS-effects on EC proliferation were attributed to the progression phase rather than the competence phase. Heparin (1, 10 or 100 micrograms/ml) significantly inhibited the proliferation of FBS (5%) stimulated EC, and the extent of inhibition was the same in both cell number and 3H-thymidine incorporation. In the 3H-thymidine incorporation every 3 hr, heparin reduced the rate of incorporation into G0-arrested EC, but did not affect the starting time of DNA synthesis. When the index of competence phase, starting time, was plotted against that of progression phase, rate of proliferation, the inhibition of heparin was attributed to the progression phase. These results demonstrate that heparin selectively inhibits the progression phase in subcultured EC of rat aorta. PMID- 1287273 TI - Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats. AB - Eurystatins A and B, which are produced by Streptomyces eurythermus R353-21, potently inhibited Flavobacterium prolyl endopeptidase (PED) with IC50 values of 0.004 and 0.002 micrograms/ml, respectively, while no inhibition was observed against another 5 proteases, even at 100 micrograms/ml. The protective effect of eurystatins A and B against scopolamine (3 mg/kg, i.p.)-induced amnesia in rats was evaluated by the step-through one-trial passive avoidance method. When administered i.p. 30 min prior to the acquisition trial, both eurystatins A, at 2 8 mg/kg, and B, at 4-8 mg/kg, significantly protected rats from the amnesic effect of scopolamine without behavioral side effects. PMID- 1287274 TI - Effects of acute administration of nicotine on convulsive movements and blood levels of corticosterone in old rats. AB - The convulsive movements, blood levels of corticosterone and pharmacokinetics of nicotine after an acute intraperitoneal injection of nicotine (5 mg/kg) were examined in young (6-week-old) and old (2-year-old) rats. In pharmacokinetic study, blood nicotine levels during the elimination phase were significantly higher in old rats than in young rats. However, the duration of convulsions and the elevation of corticosterone levels after the nicotine injection showed significant decreases in old rats compared with those in young rats. These differences of nicotine-induced responses between young and old rats may be involved in the decrease in nicotine sensitivity. PMID- 1287275 TI - Flow cytometric estimation of the effect of Ginkgo biloba extract on the content of hydrogen peroxide in dissociated mammalian brain neurons. AB - The effect of Ginkgo biloba extract (GBE) on the content of hydrogen peroxide was estimated in cerebellar neurons dissociated from rats, by means of a flow cytometer and 2',7'-dichlorofluorescein (DCF) diacetate, a fluorescent dye for intracellular hydrogen peroxide. The GBE started to reduce the DCF fluorescence of the neuron at 0.1 microgram/ml to 0.3 microgram/ml. Further increases in the GBE concentration (up to 3 micrograms/ml) produced a dose-dependent decrease in the DCF fluorescence, suggesting that GBE reduces the content of hydrogen peroxide or suppresses the reactive oxygen species (ROS) formation of cerebellar neurons. The present technique may be useful for preliminary evaluations of agents affecting the ROS formation in mammalian brain neurons. PMID- 1287276 TI - Calcium channel blocker-like action of 1,9-dideoxyforskolin in vascular smooth muscle. AB - The inhibitory effect of 1,9-dideoxyforskolin (DFK) on the contraction of rat aorta was compared with that of forskolin. DFK inhibited the contraction induced by high K+ more strongly than that induced by norepinephrine, whereas forskolin more strongly inhibited the norepinephrine-induced contraction. The inhibitory effect of DFK on high K(+)-induced contraction was antagonized by an increase in extracellular Ca2+ concentration. DFK inhibited the increase in cytosolic Ca2+ level and contraction in parallel whereas forskolin inhibited the contraction more strongly than the cytosolic Ca2+ level. These results suggest that DFK, but not forskolin, inhibits vascular smooth muscle contraction by a Ca2+ channel blocker-like action. PMID- 1287277 TI - Antiproliferative effects of the traditional Chinese medicine shimotsu-to, its component cnidium rhizome and derived compounds on primary cultures of mouse aorta smooth muscle cells. AB - Antiproliferative effects of the Japanese-Sino medicine Shimotsu-to (a combined prescription of cnidium rhizome, angelica root, peony root and rehmannia root) were investigated in the primary culture of smooth muscle cells (SMC) of mouse aorta. Fetal bovine serum (10%)-induced proliferation of primary cultured SMC was inhibited by Shimotsu-to at 4, 20, 100 or 500 micrograms/ml. The inhibitory effect was selective on SMC and due to cnidium rhizome or angelica root. The IC50 values of senkyunolide H, senkyunolide A, ligustilide and butylidenephthalide derived from cnidium were below 0.1, 1.52, 1.68 and 3.25 micrograms/ml, respectively. These results indicate that the antiproliferative effect of Shimotsu-to may depend on these cnidium-derived phthalides. PMID- 1287278 TI - KCl-depolarization potentiates the Ca2+ sensitization by endothelin-1 in canine coronary artery. AB - In Ca(2+)-free solution containing endothelin-1 (ET-1), depolarization by high KCl increased the force of contraction without any changes in intracellular calcium concentration ([Ca2+]i) in canine coronary artery. The [Ca2+]i-force relationships were examined in the absence or presence of ET-1 in 5 or 90 mM KCl. The relation curve in the presence of ET-1 in 90 mM KCl-PSS was shifted to the left and upward compared with that in 5 mM KCl. These results suggest that KCl depolarization potentiates the Ca2+ sensitization by ET-1. PMID- 1287279 TI - Executive summary: factors driving health care in Kansas. PMID- 1287280 TI - World of conflict. PMID- 1287281 TI - Telemedicine in Kansas. PMID- 1287282 TI - Pediatric cardiology: auscultation from 280 miles away. AB - New long-distance audio/video and data communications links among health-care facilities promise to reduce rural patients' travel time and waiting time for subspecialty consultations. To offer a satisfactory alternative to face-to-face examination, the long-distance system must meet the subspecialty's minimum criteria. For pediatric cardiology in particular, the system has to permit satisfactory cardiac auscultation. A preliminary test of remote auscultation that uses an electronic stethoscope involved two pediatric cardiologists, one listening hands-on with an acoustic stethoscope, the other listening independently at long distance with the electronic instrument. Taking the acoustic findings as the reference standard, the electronic stethoscope did not miss the one case of heart disease, correctly recommended echocardiogram follow up in the two cases requiring it, and agreed on 80% of the murmurs' qualitative specifics. The patients' parents also indicated that the system was highly acceptable. We are following up these results with a full-scale study of the effectiveness and parental acceptance of remote auscultation. PMID- 1287283 TI - Interactive video conferencing and Parkinson's disease. PMID- 1287284 TI - Diagnosis of childhood migraine by compressed interactive video. PMID- 1287285 TI - The technology and language of telemedicine. PMID- 1287286 TI - Preventing lead poisoning in young children. PMID- 1287287 TI - Should heparin be managed with a nomogram? PMID- 1287288 TI - [Increased fibrinogen and factor VII activity levels in patients after myocardial infarction]. AB - Functional and biochemical parameters of the haemostatic system in coronary heart disease (CHD) are still not well defined. Epidemiological studies indicate a positive correlation between fibrinogen (F) level and cardiovascular morbidity and mortality. Two independent ways of factor VII activation in the coagulation cascade suggest a special role of this factor in clot forming (Fig. 1). 22 patients (pts) under 55 yrs with a history of myocardial infarction (MT) and 22 healthy control men were studied for F level and factor VII activity (fVIIa). We found increased F level (M-363.3 mg/dl) and high level of VIIa (M-150.3%) in plasma of pts with a history of MI. Furthermore a strong positive correlation between fVIIa in plasma and F level (r = 0.62), serum cholesterol (chol) (r = 0.35), serum triglycerides (tg) (r = 0.32) (Tab. 2) was bound. Calculations were performed for all subjects: pts and control combined in one group. A possible influence of diet on fVIIa level is discussed. One should consider the usefulness of oral anticoagulants in the prophylaxis of MT. PMID- 1287289 TI - [Diurnal variability of heart rate during paroxysmal ventricular tachycardia]. AB - The aim of this study was to assess the diurnal variability of heart rate during VT. For the purpose of this investigation VT was considered to be a minimum of 3 consecutive ventricular beats in duration at a rate more than 100 bpm. From the group of 287 patients with VT during 24-hour ECG monitoring, a selection was made of 52 patients in whom episodes of monomorphic VT occurred in the day-time and night-time without any changes of the QRS morphology. Thirty one patients had ischemic heart disease, 10--dilated cardiomyopathy, 2--mitral valve prolapse and 10 patients had no evidence of heart disease. In these patients the rate of VT (HR-V), basic heart rate (HR-S) before VT, and coupling interval (CI) of VT initiating beat were measured during day-time and night-time. The mean VT rate was 170 +/- 34 bpm during day-time and 149 +/- 36 bpm during night-time (p < 0.001). The mean sinus rhythm rate was significantly (p < 0.001) greater during day-time (88 +/- 16 bpm) than at night (78 +/- 19 bpm). There was significant difference in the mean values of the CI between day-time and night-time (504 +/- 122 vs 589 +/- 181 ms). A significant correlation was noted between HR-V and HR-S at night (r = 0.73; p < 0.001) but not during day-time (r = 0.38). Thus, HR-V similarly as HR-S is greater during day-time than during night-time. Diurnal variability of HR-V may be related to changes in autonomic nervous system tone. PMID- 1287290 TI - [Diurnal variability of heart rate in paroxysmal ventricular tachycardia: discovery of real clinical importance or only electrocardiographic feature?]. PMID- 1287291 TI - [Complications of percutaneous transluminal coronary angioplasty (PTCA)]. AB - Between 1981 and 1990, 714 patients underwent 756 percutaneous transluminal coronary angioplasty (PTCA) procedures. A total of 52 patients (6.9%) had major in-hospital complications: 5 patients (0.66%) died, Q-wave or non Q-wave myocardial infarction were observed in 13 patients (1.66%) during procedure and in 8 (1%) outside the catheterization laboratory, before discharge. Because of periprocedural occlusion 11 patients (1.5%) were managed with bypass surgery, 8 (1%) had a transient occlusion that was reopened with PTCA. 21 patients (2.8%) were not ++re-dilated but managed pharmacologically. Dissection, intracoronary thrombus and previous thrombolytic treatment were often associated with occlusion. The risk of dissection was related to lesion morphology. Long-(more than 1 cm) lesion, eccentric stenosis and tortuosity of the vessel segment undergoing dilatation were risk factors for occlusive dissection. There was a high risk of side branch occlusion if its take-off was narrowed and side branch originated from the target lesion. One of the most important risk predictors is the amount of jeopardized myocardium supplied by the target coronary artery. Acute closure of an artery supplying large amount of myocardium may cause abrupt hemodynamic collapse. Hypotension secondary to the artery occlusion may cause a decrease of the flow in the other coronary arteries, leading to cardiogenic shock. Although it is important to note that patients with unstable angina, intracoronary thrombus, long and complex lesion, severe multivessel disease and compromised left ventricular function are at higher risk of acute complication, PTCA is a relatively safe procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287292 TI - [Aneurysms in acute myocardial infarction (multicenter studies)]. AB - The authors present outcomes concerning frequency of appearance and clinical course of aneurysms after acute myocardial infarction. The study population consisted of 730 patients (mean age 54 +/- 9 years) with acute myocardial infarction, including 579 men and 151 women. The diagnosis was based on the following criteria: 1) coronary artery disease history, 2) physical examination, 3) ECG, 4) 2-dimensional echocardiography, 5) biochemical data. Post-infarction aneurysm was revealed in 42 patients (5.8%, 33 men and 9 women); antero-lateral aneurysm--in 36 patients (85.7%), and inferior-posterior aneurysm--in 6 patients (14.3%). Ventricular arrhythmias in the first day of infarction had a high frequency in both groups; with aneurysm--92.9%, without aneurysm--82.2%. The frequency of arrhythmia in 21-st day of infarction decreased similarly in both groups with aneurysm--40.5%, without aneurysm--38.9%. There was no statistically significant difference among both groups. There was no correlation between localisation of aneurysms and degree of contractility disturbances of the heart muscle (dyskinesis, akinesis). Heart failure--class III and IVK (Killip-Kimball classification) occurred in 19.0% of patients with aneurysm and in 10.4% of patients without aneurysm. That was no essential correlation between localisation of aneurysms and advancement of the heart failure. PMID- 1287293 TI - [2 episodes of ventricular fibrillation in a patient with mild paroxysms of Wolff Parkinson-White syndrome]. AB - In a patient with an overt Wolff-Parkinson-White syndrome and short paroxysms of atrio-ventricular tachycardia, episodes of atrial fibrillation occurred twice at age of 21 and 24. Atrial fibrillation degenerated into ventricular fibrillation. Intravenous injection of verapamil in this patient (with a short refractory period of the accessory pathway) could have facilitated ventricular fibrillation. The patient was resuscitated successfully. Electrophysiologic study revealed double accessory pathways--in the left free wall (effective refractory period in both directions--below 200 ms) and right posterior ++para-septal localization. 20th Nov 1990 A. Biederman M.D. performed surgical dissection of both accessory pathways. In control electrophysiologic studies there was no evidence of abnormal atrio-ventricular conduction. During one year follow up the patient reported no paroxysms of tachycardia. PMID- 1287294 TI - [Recurrent bacterial endocarditis with involvement of the tricuspid valve after surgical correction of congenital heart defect]. AB - A case of recurrent tricuspid valve endocarditis after surgical closure of ventricular septal defect is presented. Intensive medical treatment lasting nearly ten years completely failed. There were still vegetations attached to the septal leaflet of the tricuspid valve with positive cultures (Ps. aeruginosa). Persistent sepsis without signs of heart failure required surgical intervention. Tricuspid valvuloplasty with excision of infected patch was successfully performed. Six months later the patient remained symptomless. PMID- 1287295 TI - [A case of direct right pulmonary artery-left atrium fistula]. AB - An unusual case of cyanotic heart disease in a 20-year-old male has been presented. Cyanosis was due to right to left shunt through direct right pulmonary artery--left atrium fistula. After successful operative ligation of the fistula, the patient got rid of cyanosis and is doing well. PMID- 1287296 TI - [Prevention of complications and the methods of increasing the safety of percutaneous transluminal coronary angioplasty (PTCA)]. PMID- 1287297 TI - [Can intravascular ultrasonography be a substitute for coronary angiography?]. PMID- 1287298 TI - [When should infectious endocarditis be surgically treated?]. PMID- 1287299 TI - [Early ventricular repolarization syndrome]. PMID- 1287300 TI - [Experience in the treatment of patients with severe heart failure using isolated ultrafiltration]. PMID- 1287301 TI - [Heart failure in acute myocardial infarction: comparing infusions of nifedipine and nitroglycerin]. AB - The impact of intravenous infusion of nifedipine and nitroglycerin on invasive central hemodynamic parameters and microcirculation was compared in 94 patients with acute myocardial infarction complicated by heart failure. The artery dilating effects of nifedipine were associated with baseline peripheral vascular tone, so the comparison was made separately in the groups with and without vasoconstriction. Nifedipine seems to be beneficial in the management of heart failure due to acute myocardial infarction in patients with systemic vasoconstriction. In patients with severe pulmonary congestion and normal left ventricular afterload, the intravenous vasodilators are preferable. PMID- 1287302 TI - [Features of the clinical and functional state of myocardial infarction patients with psychogenic silent ischemia]. AB - A total of 111 patients with myocardial infarction were studied in the early, period of the disease. Exercise and information load tests, impedance plethysmography, electrocardiography, and large-framed fluorography were performed. Among the patients with myocardial infarction who responded to information load by exhibiting transient silent ischemia, vasospastic reactions were demonstrated to be diagnosed mainly in those with posterior myocardial infarction. The patients with anterior myocardial infarction responded to psychoemotional stress mainly by showing ischemia formed under the conditions of higher myocardial oxygen uptake due to increased blood minute volume. In most patients, the area of silent psychogenic vasospastic ischemia coincided with that of infarct-related myocardium, whereas ischemic changes were largely located in the anterior left ventricular wall despite the area of myocardial necrosis when psychogenic ischemia developed with increased myocardial oxygen uptake. PMID- 1287303 TI - [Effectiveness of pre-hospital thrombolytic therapy in acute myocardial infarction]. AB - The efficacy and risk of prehospital thrombolysis for acute myocardial infarction (MI) were evaluated in a randomized trial. Patients received streptokinase, 500,000 U, and heparin, 10,000 U, intravenously within 5-10 minutes before (Group 1, n = 50) or after (Group 2, n = 50) hospital admission. One hundred patients took conventional therapy (Group 3). The mean time interval between the onset of symptoms and thrombolytic therapy was 2.2, 4.5, and 3.8 hours in Groups 1, 2, and 3, respectively (p < 0.001). Severe hemorrhages were absent. The rate of ventricular fibrillation was the same in Groups 1 and 3 prior to hospitalization. Left ventricular contractility was identical in Groups 1 and 2. By the end of the fourth week, Group 1 showed a 14% increase in ejection fraction and a 14.5% decrease in akinetic segment, these parameters substantially unchanged in Group 2. The MI size assessed by ECG and the maximum myoglobin concentrations was significantly less in Group 1 than that in Group 2. The patients from Group 1 had fewer MI complications than those from Groups 2 and 3. Three patients died in Group 1, 6 in Group 2, and 16 in Group 3. (p < 0.05). PMID- 1287304 TI - [Immunologic parameters in patients with prior myocardial infarction (findings of long-term follow-up)]. PMID- 1287305 TI - [Development of myocardial infarction in aspirin-treated unstable angina pectoris. Repeated studies of platelet aggregation and of the thromboxane prostacyclin system]. AB - Platelet functional parameters (platelet aggregation, blood circulating reversibly and irreversibly aggregated platelet complexes, thromboxane B2, 6-keto PGF1 alpha) were examined in unstable angina treated with aspirin in a daily dose of 320 mg in relation to the outcome of the disease: Group 1, stabilization and Group 2, evolving myocardial infarction. Differences were found in the baseline platelet functional parameters between the groups. The findings suggest that platelet functional parameters show a varying response to aspirin depending on the outcome of the disease. Despite the effective inhibition of thromboxane A2 synthesis, aspirin was found to fail to prevent enhanced platelet aggregatory activity in case of myocardial infarction developed during the therapy. PMID- 1287306 TI - [Clinical and functional characteristics of patients with ischemic heart disease in long-term remission of angina pectoris]. AB - Long-term (5-15-year) prospective surveys of 171 angina patients have yielded clinical, coronarographic, and bicycle ergometric criteria for predicting the favourable course of the disease. A prolonged (at least 3 years) clinical anginal remission was observed in 43 (25.1%) patients. The patients had typical features: a short (less than 6-9 months) history of classical angina, the age at the onset of CHD under 50 years; high performance during bicycle ergometric test, lack of angina after sustained so-called "accomplished" myocardial infarction. The coronarograms of patients with a long-term anginal remission most frequently displayed severe stenosis or occlusion of "unsafe" site of a large coronary artery. The duration of remission was less than 10 years if atherosclerosis also affected the remaining coronary arteries. That of remission was more than 10-15 years, if the remaining coronary arteries proved completely intact. PMID- 1287307 TI - [Use of loading tests to detect silent myocardial ischemia]. AB - A total of 74 patients with postinfarct cardiosclerosis (PC) and stable angina (SA) were examined by Holter monitoring, bicycle ergometry, echocardiography and 201Tl chloride myocardial scintigraphy and loading tests (transesophageal cardiac pacing and isometric hand exercise test). The detection rate for silent myocardial ischemia (SI) was found to be 57.1% with Holter monitoring, 52.3% by bicycle ergometry, 62.5% with echocardiography, 100% with myocardial scintigraphy with loading test and 88.8% with that without the loading test. The detection rate for PC was 33.9, 32.0, 64.7, 81.8, and 56.7%, respectively. Higher SI detection rates in postinfarct patients were more frequently observed when echocardiography and myocardial scintigraphy in combination with loading tests in patients with PC without angina. The efficiency of SI detection in patients with various coronary heart disease increases when loading tests are employed. The loading tests in echocardiography and myocardial scintigraphy ensure the most complete detection of SI in postinfarct patients without angina. PMID- 1287308 TI - [Hemodynamic basis for the bicycle ergometric test PWCaf in various clinical types of ischemic heart disease]. PMID- 1287309 TI - [Microcirculatory changes in patients with hypertensive disease caused by excessively lowered blood pressure after clofelin administration]. AB - In 20 patients with Stage II hypertensive disease, erythrocyte and platelet aggregation to response to ATP was photooptically studied, skin oxygen tension was polarographically examined, and the diameters of conjunctival vessels were microscopically measured. In the patients, excessive decreases in blood pressure were found to lead to lack of microvascular tone coordination, to increases in platelet and erythrocyte aggregation and to decreases in tissue oxygen supply. It was emphasized that the microcirculation and tissue oxygen supply should be monitored when clofelin dosages are chosen individually in the treatment of hypertensive disease. PMID- 1287310 TI - [Role of the inositol phosphate cycle in the cardioprotective effect of adaptation to intermittent hypoxia]. AB - The impact of adaptation to intermittent hypoxia of different duration (for 20 and 40 days) on the inositol triphosphate-diacylglycerol (ITP-DAG) regulatory contour in the heart was investigated. For this, isolated heart alpha 1 adrenoreactivity to phenylephrine and phospholipase (PhL-C) activities were studied in cardiac plasma membranes. On day 20 of adaptation, the heart inotropic response to phenylephrine stimulation was somewhat reduced and the activity of Ca(2+)-dependent PhL-C did not differ from that in the controls within the range of Ca2+ physiological concentrations. Forty days after adaptation, both positive inotropic responses of the heart to phenylephrine and activity of Ca(2+) dependent PhL-C were enhanced, i.e. activation of the ITP-DAG regulatory cascade occurred. Early studies have shown that a phenomenon of adaptive stabilization develops at this stage of adaptation. The phenomenon appears as a significant increase in heart resistance to thermal injury, toxic catecholamine levels, Ca2+ paradox and high Ca2+ concentrations. Thus, the revealed activation of the ITP DAG regulatory contour was accompanied by the development of a phenomenon of adaptive structure stabilization (PhASS) in the hearts of adapted animals. The findings suggest that the ITP-DAG regulatory cascade plays an important role in the cardioprotective effect of adaptation to intermittent hypobaric hypoxia and in PhASS formation. PMID- 1287311 TI - [Myocardial perfusion in mitral valve prolapse with arrhythmic syndrome]. AB - Myocardial perfusion was studied in 12 patients with mitral valve prolapse concurrent with cardiac arrhythmias by using two-dimensional 201Tl myocardial scintigraphy at rest and during exercise test. Signs of myocardial ischemia were revealed only in one case. Five patients were found to have steady-state perfusion defects whose extent correlated with the depth of mitral valve prolapse. There was an irregular distribution of myocardial blood flow, which ceased on exercise in 10 out of 12 patients. Patients with ventricular premature contraction displayed a decreased reserve of myocardial blood flow as compared to those with supraventricular premature contraction, presumably by enhancing myocardial perfusion at rest. PMID- 1287312 TI - [New-onset angina pectoris: specifics of early clinical ischemic heart disease]. PMID- 1287313 TI - [Combined (dipyridamole+transesophageal atrial pacing) electrocardiographic test in the diagnosis of minimal coronary atherosclerosis]. PMID- 1287314 TI - [Alterations in the functional activity of platelets in patients with angina pectoris during the cold test]. AB - The functional activity of platelets was examined in patients with coronary heart disease and healthy individuals during cold test (CT). Patients prone to vasospastic responses to CT exhibited platelet activation along with beta thromboglobulin release and formation of spontaneous platelet aggregates. Comparison of functional changes in platelet functional activity which occurred during cold test and intravenous ergometrine test suggest that the response to CT may be substantially higher if platelet aggregability is concurrently determined. The unidirectional changes in platelet aggregability during cold and ergometrine tests in patients with signs of dynamic coronary occlusion may indicate a relation of platelets with coronary vasoconstriction. PMID- 1287315 TI - [Carbohydrate composition of native and desialylated low density lipoproteins in the plasma of patients with coronary atherosclerosis]. AB - The monosaccharide content was examined in apoprotein B and lipids of total low density lipoprotein (LDL) preparations isolated from the blood of healthy individuals and patients with coronary atherosclerosis, as well as in desialylated and sialylated LDL obtained by affinity chromatography on Ricinus Communis Agglutinin-agarose. The glycoconjugates of total apoprotein-B of healthy subjects' LDL were found to consist of N-acetylglycosamine, galactose, mannose and sialic acid in a molar ratio of 2:1:2.5:1. The content of protein-bound neutral sugars was the same in healthy subjects and patients, while there was a lower sialic acid amount in the patients. The level of protein-bound sialic acid in patients' desialylated LDL was 2- to 3-fold lower than that in sialylated LDL. In contrast to apoprotein-B glycoconjugated, the lipid-bound carbohydrate chains of total LDL preparations had N-acetylgalactosamine and glucose, but not mannose. In total LDL from patients, the content of all lipid-bound carbohydrates was 1.5- to 4-fold lower than that in LDL from healthy subjects. In healthy subjects and in patients alike, the neutral sugar content of a lipid subfraction of desialylated LDL was lower than in those of sialylated LDL. It is concluded that atherogenic desialylated LDL differ from non-atherogenic sialylated LDL in neutral sugar levels. PMID- 1287316 TI - [Hepatic function in circulatory insufficiency. Mathematical modeling of 137I labelled rose bengal transport in the body]. AB - 131I-labelled bengali pink was used to perform radiohepatography in patients with circulatory failure. Both amplitude-time parameters of blood clearance curves and hepatograms and the generalized index of parameters of the linear 3-chambered reversible model of this tracer transport in the body indicate that the decrease of hepatic absorptive and excretory function in the presence of 131I-labelled bengali pink occurs in a direct relationship to the degree of circulatory insufficiency and developed in parallel with bilirubin metabolic disturbances. In some patients, hepatic lesion in the presence of Stages IIB-III circulatory insufficiency with signs of hepatocellular failure and cholestasis was accompanied only by moderate hepatic absorptive and excretory dysfunction against 131I-labelled bengali pink and by an increase in blood total bilirubin levels no more than that in Stage IIA circulatory insufficiency. PMID- 1287317 TI - [Stress echocardiography: new possibilities in the diagnosis of ischemic heart disease]. PMID- 1287318 TI - [Silent myocardial ischemia in arterial hypertension]. PMID- 1287319 TI - [Diagnosis and therapeutic approach to ischemic heart disease in patients with atherosclerotic lesions of the abdominal aorta and of the main leg arteries]. PMID- 1287320 TI - [Prevention of ischemic heart disease]. PMID- 1287321 TI - [New-onset angina pectoris: a case of rapidly progressive coronary atherosclerosis, correlation of clinical course and blood lipids]. PMID- 1287322 TI - [Frederick's paroxysmal phenomenon]. PMID- 1287323 TI - [Use of exercise for assessing the severity of hypertensive disease and the effectiveness of its treatment]. PMID- 1287324 TI - [Surgical aspects of vector endocrine regulation of the secretory function of the digestive system]. PMID- 1287325 TI - [Prognosis in the outcome of relaparotomy]. AB - The analysis and processing with the use of a special method of 54 direct observations and 342 case records of the patients with early postoperative intraabdominal complications were carried out. A method for syndrome prediction of the outcomes of relaparotomy has been developed. The syndromes of the most significant predictive value have been revealed: those of intoxication, respiratory and hepatorenal failure, impaired hemodynamics and electrolytic metabolism, hemocoagulation. Use in clinical practice of the method mentioned as well as the methods promoting timely detection of the intraabdominal complications permitted to reduce lethality after relaparotomy from 21.4 to 15.3%. PMID- 1287326 TI - [The value of biochemical indices of the blood in early diagnosis of gastric cancer]. AB - The results of biochemical blood analysis in 75 patients with I-II stage gastric cancer have been analysed. The control group was comprised of 210 patients with gastritis, callous ulcer and polyps of the stomach. By means of a correlation regression analysis, the non-linear relations between I-II stage gastric cancer and biochemical indices of the blood were revealed. The highly significant indices for diagnosis of the disease in mass examination of the population have been developed. PMID- 1287327 TI - [Three methods of placing a single-row layer-by-layer everted intestinal suture]. AB - The three methods for placing a single-row layer-by-layer everted intestinal suture with the suture ligature knots situated in a different manner relative to anastomotic surfaces are presented. Using the methods suggested, 53 patients were operated on, who underwent formation of 87 anastomoses. The results of studies indicate that the use of a single-row layer-by-layer everted suture permits to reduce considerably the incidence of postoperative complications, promotes early restoration of a function of the organ operated on. PMID- 1287328 TI - [Importance of immunologic protection factors in predicting the development of purulent septic complications after appendectomy]. AB - In 66 patients with acute appendicitis, the immunocompetent system was studied in dynamics, significant decrease in all the parameters considered before and at different time after the operation was revealed. In patients with complicated forms of the disease, disorders in immunity were more pronounced, and didn't disappear by the moment of clinical recovery. Sharp reduction (more than 40-50%) of both humoral and cellular links of immunity by day 1 and 3 after the operation can be used as an early prognostic sigh of the development of a postoperative wound suppuration. PMID- 1287329 TI - [Specifics of resistance dosing at expiration in spontaneous respiration with positive pressure at the end of expiration in the postoperative period in obese patients]. AB - The indications and regimens of spontaneous respiration with positive pressure at the end of expiration (SR with PPEE) in patients with morbid obesity are not established. The individual selection of resistance at expiration is necessary. In 53 patients, the selected resistance at expiration has proved to be the optimal, contributing to significant improvement of parameters of pulmonary ventilation without deterioration of hemodynamic indices. An inverse dependence of the values of optimal resistance at expiration and excess in ideal body mass was established. By multiplying the values mentioned, the K coefficient is obtained equal to 530.3 + 7.66. In patients over 60, K was 400.3 +/- 11.52. The use of a nomogram (in numerical and graphic versions) to dose resistance at expiration in patients with concomitant morbid obesity contributed to significant improvement of the indices of pulmonary ventilation and gas exchange without disorders in hemodynamics after seances of SR with PPEE. PMID- 1287330 TI - [Managing the postoperative period after gastric resection in an experimental study]. AB - In 60 mongrel dogs of both sexes, gastric resection was performed under endotracheal narcosis. Depending on peculiarities of conducting the postoperative period, the animals were subdivided into three groups: in group 1 animals, total parenteral nutrition was used, in group 2--total enteral nutrition, in group 3- combined therapy. Combined parenteral (dextrans) and enteral (energetic and plastic substrates) administration of drugs and nutrients is an optimal method of corrigative therapy after resection of the stomach. PMID- 1287331 TI - [Gastrectomy at the peak of gastric bleeding]. AB - The technique for performance of gastrectomy under conditions of emergency surgery permitting to shorten the duration of intervention and increase its effectiveness is presented. Gastrectomy was performed in 7 patients with gastric cancer complicated by profuse bleeding. All the patients are alive, no anastomotic suture failure occurred. PMID- 1287332 TI - [Intraabdominal hemorrhage after surgery on the abdominal organs requiring relaparotomy]. AB - The results of 76 relaparotomies performed for intraabdominal postoperative hemorrhage after emergency and elective operation on the abdominal organs are presented. The clinical features, diagnosis of profuse and capillary postoperative hemorrhage, causes and indications for relaparotomy performance are considered. Lethality in intraabdominal postoperative hemorrhage was 18.4%. PMID- 1287333 TI - [Simultaneous surgeries in the treatment of stomach and duodenal diseases]. AB - The results of diagnosis and treatment of diseases of the stomach and intestine associated with diseases of the abdominal organs: hiatal hernia (97 cases), commissural disease of the peritoneum (31), calculous cholecystitis (28), abdominal wall hernia (22) are presented. In 34 patients, 3 and more diseases were revealed. Simultaneous operations were performed in 181 patients. At the long-term period, a good result was noted in 68.6%, a satisfactory one--in 25.5%, and unsatisfactory result--in 5.9%. The substantiated performance of simultaneous operations in patients of the given category is a perspective trend in surgery, it ensures the high medico-social and cost effectiveness of treatment. PMID- 1287334 TI - [Early diagnosis and treatment of a pyloroduodenal ulcer complicated by stenosis of gastric outlet]. AB - Treated were 193 patients with pyloroduodenal ulcer complicated by stenosis of gastric outlet. Compensated stenosis was noted in 14 (7.2%) patients, subcompensated--in 147 (76.2%), decompensated--in 30 (15.5%), gastric tetany--in 2 (1.04%). Studied were the immunologic indices, peripheric blood flow by means of a roentgenologic method under conditions of double contrasting and artificial hypotony, gastric and duodenal function, bioelectric activity--by the method of duodenokinesiography. Gastric resection was performed in 87 patients, vagotomy with drainage operation and without it--in 82, gastroenterostomy--in 14, antrum resection with vagotomy--in 12, Roux resection of the stomach--in 2. The postoperative lethality was 1%. Good and excellent results after gastric resection were noted in 82.1%, after vagotomy--in 88.4% of the patients. PMID- 1287335 TI - [Perforation of a giant duodenal ulcer]. AB - The results of operative treatment of 20 patients with a perforated giant duodenal ulcer have been analysed. The difficulties associated with closure of a perforated hole and duodenal stump management in performance of gastric resection were noted. It was established that closure of a giant perforated duodenal ulcer was a palliative measure, which saved the patients from death but entailed the disease recurrence requiring reoperation. PMID- 1287336 TI - [Immediate result of surgical treatment of ulcer disease in morbidly obese patients]. AB - From 1975 to 1989, 97 patients with ulcer diseases and concomitant obesity were operated on at the Tashkent branch of the All-Union Scientific Surgical Centre, Academy of Sciences of the USSR. The patients with a gastroduodenal ulcer, II and higher degree of morbid obesity accounted for 2.4% of the total number of patients operated on for ulcer disease. Gastric ulcer was diagnosed in 20 patients, a duodenal one--in 77. All the patients were operated on for disease complications. Of them, 36 underwent Billroth-II gastric resection, the remaining patients--Billroth-I gastric resection and truncal vagotomy with drainage operation. The best immediate result was noted after performance of truncal vagotomy with drainage operation. Use of gastric resection in a given category of patients is accompanied by the development of a large number of local and general complications. PMID- 1287337 TI - [Indices of acid-base and pepsin-acid coefficients in the gastric contents of patients with duodenal ulcer]. AB - The indices of acid-base and pepsino-acid coefficients (ABC and PAC) in 99 patients with a duodenal ulcer, who previously underwent closure of its perforation and in 22 patients with uncomplicated course of the disease were studied. The control group included 22 healthy subjects. In patients after closure of a perforative duodenal ulcer, the low ABC and PAC indices may be indicative of the absence of stable disease remission and possibility of the development of a repeated complication. PMID- 1287338 TI - [Surgical treatment of complicated ulcer disease of the stomach and duodenum at the health department of a metallurgical factory]. AB - The case records of 419 patients with complicated gastric and duodenal ulcer disease were analysed. Frequent asymptomatic course of the ulcer disease was noted in workers of the metallurgical and engineering industry. Different modifications of Billroth resection of the 2/3 of the stomach were used in 240 patients, selective proximal vagotomy (SPV) with ulcer excision--in 87, transverse gastric resection with preservation of the pyloric sphincter--in 30, closure of a perforative hole--in 60, closure of a perforative hole with excision of the ulcer margins and bilateral truncal vagotomy--in 2. The most favourable long-term result was noted in patients after SPV with ulcer excision and transverse gastric resection with preservation of the pyloric sphincter. PMID- 1287339 TI - [Primary diseases of the greater omentum in children]. AB - The results of treatment of 12 children with primary acute diseases of the greater omentum, in whom preoperative diagnosis is difficult, have been analysed. At operation, primary omentitis was revealed in 4 children, in 6--torsion of the omentum, in 2--its idiopathic infarction. Two more children were operated on for lymphangioma of the greater omentum. The result of treatment is positive, and prognosis of the disease is favourable. PMID- 1287340 TI - [Loop colostomy in patients with cancer of the colon and rectum]. AB - At the clinic of Scientific Research Institute of Proctology, Ministry of Public Health of Armenia, in 97 patients with complicated cancer of the colon and rectum, a two-barrel loop colostomy was created for the recent 10 years. Use of intraperitoneal method contributed to 3-fold decrease in incidence of postoperative purulent complications. Irrigation of a tumour site with antibacterial preparations in perifocal inflammation of colonic cancer together with carrying out the complex antibacterial therapy permits to perform the radical operations. PMID- 1287341 TI - [Gastric resection in the surgical treatment of uncomplicated duodenal ulcer]. PMID- 1287342 TI - [Surgical treatment of patients with giant gastric ulcer]. PMID- 1287343 TI - [Diagnosis of intestinal fistula]. PMID- 1287344 TI - [Associated hemorrhage into the abdominal cavity]. PMID- 1287345 TI - [Perforation of acute ulcer after stomach resection]. PMID- 1287346 TI - [Annular pancreas in a patient with complicated duodenal ulcer disease]. PMID- 1287347 TI - [Multiple associated diseases in patients with duodenal ulcer disease]. PMID- 1287348 TI - [Foreign body in the gastric wall as a cause of profuse gastric bleeding]. PMID- 1287349 TI - [Rare complication in a patient after stomach resection]. PMID- 1287350 TI - [A reconstructive operation in peptic ulcer on gastroenteric anastomosis penetrating into the pancreas and transverse colon]. PMID- 1287351 TI - [Relaparotomy in patients with perforating gastroduodenal ulcers]. PMID- 1287352 TI - [Strong's operation in the surgical treatment of ulcer disease]. PMID- 1287353 TI - [Venous infarction of the small intestine]. PMID- 1287354 TI - [Leiomyoma of gastric fundus as a cause of profuse bleeding]. PMID- 1287355 TI - [Leiomyoma of the large intestine in a child]. PMID- 1287356 TI - [Rare location of the vermiform process]. PMID- 1287357 TI - [The effect of selective proximal vagotomy on mucus production of the stomach in pyloroduodenal ulcer]. AB - Secretion of the main component of gastric juice mucus-fucoglycoproteins (FGP) in uncomplicated and complicated by stenosis of gastric outlet ulcer disease of the stomach and intestine, the effect of selective proximal vagotomy (SPV) and drainage operations on FGP exchange were studied. Dependence of fucose production on severity of the course of ulcer disease has been established. Early after SPV, preservation of FGP concentration in the gastric juice at initial level and significant decrease in their hour production were noted. FGP concentration in patients with its low initial values restored within the first year of follow-up, debit--later on. The data obtained can be used in assessment of the SPV results, and in revealing the patients with high risk for development of ulcer disease recurrence. PMID- 1287358 TI - [Social costs of visual handicap and blindness. Rehabilitation resources for blind patients]. AB - The number of blind and partially sighted persons in Germany is growing. Increasing social cost and human suffering are related. Measures to counteract this development (e.g. prevention, rehabilitation) are needed. This work gives an overview of the social cost of visual impairment; rehabilitation efforts and needs for eye diseases are considered. MATERIALS AND METHODS: Data from several sources have been analysed in regard to social cost of blindness and rehabilitation efforts for eye diseases: e.g. from the Bavarian and Federal statistical agencies (number of blind and partially sighted), form the German veterans administrations (number of early retired) etc. The results relate to the former Federal Republic of Germany before unification; data from the five new states are not yet available. RESULTS: 1. social cost: The funds needed for blindness compensation payments increased steadily; new figures from Bavaria indicate that in Germany a total of 1,000,000 DM is needed. As a trend the yearly rise over the last 10 years was 6% in Bavaria. Indirect social cost ist caused by early retirement of blind or visually handicapped people; yearly 1% (2000 cases) of all early retirement is due to eye diseases. 2. rehabilitation efforts: For the annual incidence of blind and partially sighted--an estimated 17,000 blind and 50,000 partially sighted--only 12,000 rehabilitation measures are provided in Germany. For the age group over 65 years (which makes up to 60% of all visually impaired) only 800 rehabilitation measures are being completed yearly. In the ophthalmology sector the provision of low vision aids to visually handicapped people is incomplete. A maximum of 60% of all practising ophthalmologists in Bavaria provide this service. On the basis of own data (and from the medical service of medical assistance insurances) it is obvious that 20-50% of the prescribed low vision aids do not fit the requirements of the visually handicapped. In general too high a magnification is prescribed. CONCLUSIONS: More visual rehabilitation services are needed to cope with the growing demand, especially for low vision aids. A prerequisit for a higher coverage with low vision aids is a better reimbursement of the prescribing ophthalmologist by medical assistance insurances. PMID- 1287359 TI - [Short-term effect of megadose steroid therapy in optic neuritis]. AB - 15 patients with unilateral optic neuritis and 2 patients with bilateral optic neuritis were treated with 1000 mg methylprednisolone i.v. per day for 5 days. In the cases of unilateral optic neuritis, visual acuity was reduced to < or = 0.1, in those with bilateral optic neuritis to < or = 0.6 in the better eye. The treatment was started one to 70 days after the onset of the neuritis. We examined whether vision recovered rapidly during the treatment. As a rapid recovery we defined a fourfold improvement on a logarithmic scale during the 5 days of methylprednisolone medication. Such a rapid recovery was found in 11 of the 15 patients with unilateral and in 1 of the 2 patients with bilateral optic neuritis. A similar recovery was not found before and after the treatment interval. Although we did not have a control group, the correlation in time between the therapy and the rapid recovery suggests that the megadose steroids were effective in our patients. This interpretation is compatible with the results of the randomized controlled multicenter trial of Beck et al. (New Engl. J. Med. 326:81, 1992): However, the beneficial effect was seen up to 6 months only; one year after treatment, visual functions did no longer differ between the megadose and the placebo groups. Low-dose oral steroids did not improve visual function at any time and carried a higher risk for new episodes of neuritis, compared to placebo. Therefore, the "traditional" low-dose steroid therapy for optic neuritis has become obsolete. PMID- 1287360 TI - [Evaluation of the image quality of bi- and multifocal intraocular lenses with a new optical system]. AB - By means of a new optical device developed by Reiner, an "optical implantation" of 6 different bi- and multifocal intraocular lenses (MIOLs) was performed in 20 young healthy subjects, and results were compared with those of a monofocal reference IOL. The following parameters were investigated: distance and near visual acuity, depth of focus and contrast sensitivity. The median of distance visual acuity was 1.0 in all IOLs with the exception of a 7-zone refractive MIOL (0.75). Near acuity without near addition was 1.0 in all MIOL models; through focus curves of all MIOLs showed an increase in depth of focus with a typical two peak course. Contrast sensitivity at high contrasts was reduced for the 7-zone model, but contrast sensitivity at low contrasts was significantly reduced for all MIOLs, except the 2- and 3-zone refractive models. PMID- 1287361 TI - [Venous anomalies within the myelinated retinal nerve fiber area]. PMID- 1287362 TI - [Keratosis follicularis spinulosa decalvans (Siemens I syndrome), initial results of molecular genetic research]. PMID- 1287363 TI - Evolution of metabolic pathways by chance assembly of enzyme proteins generated from sense and antisense strands of pre-existing genes. AB - In order to get an insight into the evolutionary aspect of metabolic pathways, especially of the ubiquitous glycolytic pathway, we have carried out an extensive search of sense-sense and sense-antisense similarities for enzyme proteins in the glycolytic pathway, the pentose phosphate cycle, alcohol and lactate fermentation pathways and the TCA cycle. This investigation of amino acid sequences reveals a curious pattern of similarity relations; no similarity can be found between the enzyme proteins in a section of the glycolytic pathway where the glyceraldehyde-3 phosphate or even glycerol-3-phosphate is converted into the pyruvate while many examples of sense-sense and sense-antisense similarities are found even between enzyme proteins in distant blocks, e.g. between the proteins in the TCA cycle and those in the pentose phosphate cycle, as well as between the functionally associated proteins in each of these blocks. Complementary to this characteristic pattern of amino acid sequence similarity, the search for similarities of nucleotide sequences also finds that the similarities of glycolytic enzyme genes, some sense-sense and others sense-antisense similarities, are concentrated on the nucleotide sequences of prokaryotic 16S or eukaryotic 18S ribosomal RNA gene with its flanks, although some of the copy sequences are also found in transfer RNA genes as well as in 23S or 26S ribosomal RNA gene. These results strongly suggest that the metabolic pathways have been developed by the chance assembly of enzyme proteins generated from the sense and antisense strands of pre-existing genes, e.g. the fermentation pathways and pentose phosphate cycle by the proteins from the genes of enzymes in the glycolytic pathway and the TCA cycle from all these successively increased genes, ascribing the origin of metabolic enzyme genes to the close relation between the glycolytic enzyme protein genes and the RNA gene cluster. PMID- 1287364 TI - A model for simulating cognate recognition and response in the immune system. AB - We have constructed a model of the immune system that focuses on the clonotypic cell types and their interactions with other cells, and with antigens and antibodies. We carry out simulations of the humoral immune system based on a generalized cellular automaton implementation of the model. We propose using computer simulation as a tool for doing experiments in machine, in the computer, as an adjunct to the usual in vivo and in vitro techniques. These experiments would not be intended to replace the usual biological experiments since, in the foreseeable future, a complete enough computer model capable of reliably simulating the whole immune would not be possible. However a model simulating areas of interest could be used for extensively testing ideas to help in the design of the critical biological experiments. Our present model concentrates on the cellular interactions and is quite adept at testing the importance and effects of cellular interactions with other cells, antigens and antibodies. The implementation is quite general and unrestricted allowing most other immune system components to be added with relative ease when desired. PMID- 1287365 TI - Correlations between the coding and non-coding regions in DNA. AB - In this paper various aspects of codon usage and k-tuple correlations in the DNA are compared. It is shown that the correlation structures of the coding and the non-coding regions are very similar and that codon usage is reasonably specific for large groups of organisms. These results suggest that the origin of codon usage is related to the origin and structure of the DNA. PMID- 1287366 TI - Long-range doublet correlations in DNA and the coding regions. AB - Long-range two-body correlations in a DNA sequence should in theory approach a constant value very rapidly with increasing value of the correlation length. It is shown that for most DNA sequences, the long-range correlations exhibit oscillations superimposed on the constant background. These oscillations persist for very large correlation lengths. The oscillations are shown to be three-point cycles and are related to the coding regions in the DNA. A method for discovering the coding regions in DNA sequences is presented. The limitations of the method are discussed. PMID- 1287367 TI - Plasmid copy number control: a case study of the quasi-steady-state assumption. AB - Perelson & Brendel (1989, J. molec. Biol. 208, 245-255) have proposed kinetic models for the control of plasmid copy number, based on experiments by J. Tomizawa and his associates. The quasi-steady-state assumptions (QSSA) made in the analysis of these models are justified in the present paper, thereby providing an example of how QSSA can provide a powerful and reliable tool in the analysis of biological kinetics. PMID- 1287368 TI - Temporal and spatial scales in epidemiological concepts. AB - Traditional concepts in epidemiology are reviewed from ecological, cultural, and logical perspectives. In zoological epidemiology (including the study of human and livestock diseases caused by pathogens), temporal and spatial scales are typically not used in definitions, by hypotheses, and theories concerning epidemic and endemic diseases. The same is true for botanical and theoretical epidemiology, although these two subdisciplines use a different definition of an epidemic than does zoological epidemiology. If hypotheses are to be tested and implemented, more precise concepts that include general temporal and spatial scales are needed. Criteria proposed here for identifying temporal and spatial scales are based on the need for consistency of observation and ecological validity. Consistency of observation depends upon the relative life cycles of the hosts and pathogens and upon the environmental effects that lead to stable or unstable population structures. Pathogens are classified as absent, sporadic, or persistent (endemic). Epidemics can occur in the latter two cases but require a separate evaluation. A definition of an epidemic based on temporal and spatial scales and statistics is proposed for use by all subdisciplines. An epidemic occurs when an indicator variable reaches a statistically unusually high value due to transmission of a pathogen in an ecologically proper space-time unit. Threshold theorems in botanical and theoretical epidemiology are also discussed. These proposals do not directly affect modeling, but changes to hypotheses may influence model analyses. PMID- 1287369 TI - Evaluation of social problem-solving abilities in rural home health visitors and visiting nurses. AB - A number of studies have shown the value of using home health visitors and visiting nurses in intervention outreach programs designed to provide pre- and postnatal care for low-income women. The purpose of this study was to compare the abilities of a selected sample of professionally trained nurses and nonprofessionally trained home health visitors to suggest and prioritize solutions to a medical dilemma. Data were gathered by the use of a Practical Solutions Test and a Ranking Solutions Procedure. The subjects for the study were 77 females residing in rural counties in West Alabama. The four study groups were comprised of: (a) trained home visitors with 0 to 6 months of experience, (b) trained home visitors with more than 6 months of experience, (c) professionally trained nurses, and, (d) a control group of women with no training or experience. Data were analyzed using one-way analysis of variance (ANOVA). The findings suggest that all of the trained groups were able to generate more solutions to a typical client medical dilemma than could the control group: F(3.76) = 11.79; p = .0001. Faced with the same medical dilemma, the nursing group was more likely to suggest medical options over socioemotional solutions than were the home visitors: chi 2(3.76) = 9.41; p = .02. The nurses also prioritized the solutions differently by ranking them in a different sequence. PMID- 1287370 TI - Infant gender and sibling dyad influences on maternal separation anxiety. AB - The purpose of this longitudinal study was to compare maternal separation anxiety by gender of infants and sibling dyad in 40 employed, second-time mothers. Subjects completed two parallel measures of separation anxiety, the Maternal Separation Anxiety. Scale (MSAS) and the Interview-Based Rating Scales (IBRS). The mothers completed the MSAS when the first infant was born and again 2 years later when their second infant was 7 months old (mean age). Following completion of the MSAS (for the second child), the mothers were interviewed and rated on their separation concerns (IBRS) related to both children. No gender differences were noted when t-tests were computed on mothers' MSAS mean scores, but the IBRS revealed that mothers of second-born sons were significantly more anxious about separation (t = 2.01, p < .05) than were mothers of second-born daughters. One way General Linear Model comparisons of both measures, for the four sibling dyads, revealed significant differences related to the dyad composition. Mothers of girl/girl dyads were significantly more anxious about separation as measured by the MSAS. On the IBRS, mothers of boy/boy dyads were significantly more anxious and mothers of boy/girl dyads were significantly less anxious when compared to mothers of the other dyads. PMID- 1287371 TI - Preliminary findings: a maximum oral feeding time for premature infants, the relationship to physiological indicators. AB - Oxygen saturation (SaO2) values, pulse rate and respiratory rate (RR) were monitored using a pulse oximeter during feeding sessions for 21 preterm infants (mean postconceptual age 35.61 weeks) at 3-minute intervals. The purpose of the study was to determine if there is a maximum stressful nippling time span within the context of the prescribed amounts of formula taken and to determine and verify the relationship between: (a) nipple feeding and clinical stress reactions to these variables, (b) the amount of formula taken in the first 3 minutes and (SaO2) values, PR, and RR; and (c) the birthweight of the infant and the length of time from birth to the initial nipple feed. Although the repeated analysis of variance failed to show a significant change (p > .05) from baseline in SaO2, PR, and RR, correlational analysis showed a significant relationship between the amount of formula taken in the first 3 minutes of feeding and the respiratory rate (r = .69, p = .001). Since no significant declines were detected across time in the physiological measures, a maximum stressful nippling time was not established from these data. As expected, a significant relationship between birthweight and the length of time from birth to the initial nipple feed was revealed (p < .05). PMID- 1287372 TI - Maternal adaptation during pregnancy among adult early, middle, and late childbearers: similarities and differences. AB - Women 20-24 (n = 10), 25-29 (n = 13), and 30 and over (n = 18) were interviewed and their responses compared on six variables: maternal-fetal relationship, quality of the marital relationship, preparation for motherhood, attitude towards the pregnancy, maternal role conceptualization, and motivation for motherhood. Later childbearing was significantly related to three variables: motivation for motherhood, maternal-fetal relationship, and maternal role conceptualization. Women 25-29 years old were more similar to women 30 years and older than to younger women. The data suggest that young adult women 20-24 years old may experience more difficulty in prenatal adjustment to the maternal role than those 25 and older. Data also suggest the need to reconsider the traditional age comparative split of the 20s versus the 30s. PMID- 1287373 TI - Effects of lemakalim and thalium on early afterdepolarization in mouse atrial fibers. AB - The effects of lemakalim (BRL 38227) and thallium ion (Tl) on action potential (AP) and on early afterdepolarization (EAD) were studied in mouse atrial fibers. Under treatment with lemakalim (25 mcM) or Tl (0.2 mM), the AP was not significantly changed except for the reduction of duration of AP (APD). EAD induced by 3.0 mM K superfusion was abolished by 50 mcM lemakalim and only partially inhibited or was not effected under 25 mcM lemakalim. However, EAD was abolished completely and rapidly by Tl treatment. With addition of K concentration in superfusate to 5.0 mM the EAD could only be partially inhibited. By further increasing the K concentration to 7.0 mM the EAD could be completely abolished. It is suggested that the activator of outward current could inhibit EAD as well as the blockers of inward currents. PMID- 1287374 TI - Interactions between thiopental and volatile anesthetics (halothane and isoflurane) in isolated heart preparations of the rat. AB - Thiopental uptake into heart muscle tissue was studied in spontaneously beating rat hearts (Langendorff preparation, 0.13-0.27 mmol/l thiopental in the perfusion fluid). Up to 0.19 mmol/l the concentration of thiopental in heart muscle tissue was increased vs. control when halothane (0.8 vol%) was present. Using a constant thiopental concentration (0.13 mmol/l) and 0.8, 1.5 or 2.0 vol% halothane +12%, +29% or +43% more thiopental was taken up into heart muscle tissue compared to the control. This increased uptake was not seen in the presence of 1.2 and 2.0 vol% isoflurane. Frequency of right rat atria was decreased by increasing thiopental concentrations (0.02-0.23 mmol/l in the incubation medium). Halothane (0.8 and 1.5 vol%) and isoflurane (1.0 and 2.0 vol%) alone had no influence on frequency of right atria. Both volatile anesthetics additionally increased the negative chronotropic action of thiopental when the corresponding higher concentration was applied. Contractile force of left rat atria was decreased concentration-dependently by thiopental (0.02-0.23 mmol/l). Halothane and isoflurane alone decreased contractility. Dependent on the concentration used, both volatile anesthetics further increased the negative inotropic action of thiopental, yet preferentially at higher barbiturate concentrations. PMID- 1287375 TI - Cardiovascular alterations in the hypothyroid rat. AB - We conducted the present studies in intact animals to assess alterations in integrated cardiovascular function due to hypothyroidism. Rats were surgically thyroidectomized or sham operated. Most obvious among the alterations detected under resting conditions was the bradycardia present in hypothyroid animals. Cardiac output was significantly reduced by slower heart rate; however, mean arterial blood pressure and left ventricular +dP/dt were maintained. Total peripheral resistance was increased in hypothyroid animals. Functional responsiveness to hemodynamic challenges unmasked additional characteristics. Thyroidectomized animals had normal stroke index-left ventricular end diastolic pressure relationships in response to rapid volume infusion. Peak left ventricular +dP/dt response to brief aortic occlusion was attenuated in thyroidectomized animals. Hypothyroid rats failed to augment left ventricular dP/dt in response to isoproterenol challenge. Moreover, isoproterenol failed to reduce total peripheral resistance in the hypothyroid rat. Therefore, the hemodynamic responses observed in the intact, hypothyroid animal are consistent with the presence of (a) decreased cardiac contractile protein ATPase, (b) reduced calcium uptake by cardiac sarcoplasmic reticulum and (c) altered vascular adrenergic receptors. Many cellular and subcellular defects are compensated by integrative mechanisms operating under resting conditions, while other defects are unmasked only when examined in the intact, functional cardiovascular system undergoing hemodynamic challenge. PMID- 1287376 TI - The effect of loop of Henle diuretics on the tubuloglomerular feedback mechanism. AB - Increases in the delivery of solute to the loop of Henle result in increased reabsorption, vasoconstriction of the afferent arteriole, and a reduction in the glomerular filtration. Although the details of this tubuloglomerular feedback (TGF) mechanism are not completely worked out, it appears certain that alterations in reabsorption by the loop of Henle are critical to its operation. In the following study, we assessed the effect of several different loop of Henle diuretics on the response of the TGF mechanism. The function of TGF was monitored by measuring the stop-flow pressure (SFP) in the early proximal tubule in response to alterations in perfusion rate through the loop of Henle. All drugs were given directly into the loop of Henle in a concentration of 10(-4) M. With control solutions, SFP fell in a sigmoidal fashion over a perfusion range of 5 to 45 nl/min. When furosemide was added to the perfusate at a dose of 10(-4) M, SFP did not change. Bumetanide had an effect similar to furosemide, but muzolimine failed to inhibit the reduction in SFP over the perfusion range. Three experimental compounds were tested. All three cause diuresis when administered orally to animals. MK447 had no effect on SFP, but its metabolite, MK447-SO4, had an effect similar to furosemide. Another compound with modest diuretic effects, ICI 207,828, actually increased the response in SFP. Two distal diuretics, hydrochlorothiazide and amiloride, had no effect on SFP. The response of SFP to all these compounds correlated with its measured effect on loop reabsorption of sodium. Furosemide, bumetanide and MK447-SO4 significantly reduced sodium reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287377 TI - Effects of the new hypolipidemic agent F 2833 on plasma lipoprotein levels in normal and hyperlipidemic hamsters. AB - The present study analyzed the effects of the new hypolipidemic agent, F 2833, in male golden Syrian hamsters fed a standard diet or a diet supplemented with 0.06% cholesterol and 20% coconut oil. F 2833 did not detectably modify the blood lipid parameters studied in hamsters receiving the standard diet. After 28 days, the hyperlipidemic diet in untreated animals significantly increased plasma cholesterol, triglycerides and phospholipids (by 91, 138 and 61%, respectively) and in the different lipoprotein classes. Treatment with F 2833 (150 and 300 mg/kg/day) caused a dose-dependent reduction of the blood lipid parameters studied. At the higher dose, this decrease was significant for cholesterol (27%), triglycerides (48%) and plasma phospholipids (27%). With regard to the different classes of lipoproteins, a significant drop in cholesterol was observed in VLDL (38%) and LDL (29%), while that in HDL (22%) was not significant. Triglycerides were significantly lowered in all lipoprotein classes with a more pronounced effect in the VLDL pool (53%). F 2833 thus decreased plasma lipids in hamsters that were fed on hyperlipidemic diet to normal values observed in animals fed a standard diet. These results confirm and extend findings previously obtained in other animal species in which F 2833 was also shown to be an effective hypolipidemic drug. PMID- 1287378 TI - A double stopcock technique for repeated sampling of venous blood. AB - Repeated sampling for measurement of venous blood levels of hemoglobin, hematocrit, plasma hemoglobin, potassium and ibuprofen with a novel method of phlebotomy, the double stopcock technique (DST), was compared to heparin lock (HPL), Angiocath with obturator (AOB) and direct venipuncture (DVP) techniques. There were 12 normal subjects in this randomized, three-way crossover trial. During each portion of the crossover, simultaneous samples for hemoglobin, hematocrit, plasma hemoglobin, potassium and ibuprofen were taken from each phlebotomy site prior to and after oral dosing with 400 mg ibuprofen. The DST was the best acceptable method based on the assessment of comfort by the subjects, followed by the AOB, HPL and DVP techniques. The least amount of blood waste was with the DST. The degree of hemolysis (as shown by plasma hemoglobin and potassium) was comparable across all techniques. Across all of the techniques, measurement of hemoglobin, hematocrit and ibuprofen levels using DST, HPL and AOB yielded lower levels than DVP. These changes were small and were not clinically significant, although statistically significant in some cases. The authors conclude that when there is need for frequent, rapid and repetitive venous blood sampling with minimal blood wastage and patient discomfort, the DST should be considered. PMID- 1287379 TI - Daily variation and effects of ambient light and circadian factors on the human light reflex. AB - Measures of pupillary size and the dynamic light reflex are safe and noninvasive methods to quantify and characterize the mechanism and site of drug action. The effects of variations in ambient light and time of day on pupillary measures were determined. In dark adapted volunteers (n = 13), ambient light was incrementally increased at < 0.1, 4, 40, 100 and 200 foot-candle (ftcd). Subjects adjusted to each light level for 1 min before the light reflex was elicited. Replicate measures were collected with the contralateral eye open and covered with an opaque patch. Data were collected every 3 h between 6 a.m. and 9 p.m. The prestimulus diameter of the dark adapted pupil averaged 6.4 mm at < 0.1 ftcd and 2.3 mm at 200 ftcd. Constriction amplitude decreased with increases in ambient light from 2.1 mm (< 0.1 ftcd) to 0.2 mm (200 ftcd) while constriction and dilatation velocities decreased from 7.7 to 2.8 mm/sec and 4.3 to 2.8 mm/sec, respectively. Time of day effects were small but statistically significant and the interaction of ambient light and time of recording suggests the pupil is differentially sensitive to ambient and phasic light stimuli over the course of the day. A patch over the contralateral eye increased pupil size and velocities of the light reflex. In a second study, 10 volunteers were tested twice a day at 4 and 80 ftcd for four days. While there was wide between subject variability, the within subject differences were small. Such baseline data may be useful in describing the normal variations in these increasingly popular indices of drug action. PMID- 1287380 TI - Drug disposition in the elderly: gerontokinetics. PMID- 1287381 TI - Festschrift for John J. Ohala. PMID- 1287382 TI - Vowel categorization and the critical band. AB - Using the concept formation paradigm, two series of experiments were conducted to test the hypothesis that the critical band (CB) was a factor in learning to make absolute discriminations of vowels. The specific hypothesis being examined was that the CB is a psychoacoustic boundary in learning to make vowel categorizations, and that learning absolute discriminations of pairs of vowels that differ in one of their formants by one bark or more is significantly easier than learning absolute discriminations of vowels that differ by less than one bark. Subjects were given the task of learning to identify paired sets of synthesized vowels that differed in either F1 or F2 by 0.4, 0.6, 0.8, 1.0, or 1.2 bark. The results of these experiments suggest that the critical bandwidth is not a natural psychoacoustic boundary in the learning of vowel categories, and also that subjects seem better able to learn distinctions involving differences in F1 than distinctions involving differences in F2. The discussion raises the possibility that vowels that differ by less than one bark may not be perceptually viable because of such factors as ambient noise, articulatory constraints, and coarticulatory influences. Some evidence from Dutch and French is presented in support of this conjecture. PMID- 1287383 TI - Perceptual restoration of filtered vowels with added noise. AB - Perceptual restoration is a well-known phenomenon for speech segments in context, but less is known about the effect for stimuli that occur without a linguistic context. The current study investigated restoration in the perception of isolated vowels. Vowels excised from natural speech were lowpass filtered (1000 Hz), which removed the high F2 characteristic of front vowels. This resulted in high rates of front to back vowel confusions; however, these errors were reduced when highpass filtered noise was added to the lowpass filtered vowels. Although the reduction in errors was accompanied by an increase in back to front vowel errors, addition of noise led to improved performance overall. These results suggest that listeners "restored" the high F2 of front vowels in the noise condition, despite an absence of linguistic context to influence restoration, and that addition of noise led to more effective utilization of cues below 1000 Hz. PMID- 1287384 TI - The phonological representation of [voice] in speech perception. AB - This paper examines to what extent phonological representations affect word identification. The contrast under investigation involves the interaction between voicing and vowel length in Dutch. Dutch has underlying contrasts both in obstruent voicing and in vowel length. The voicing contrast is neutralized on the surface in syllable-final position. Also, both long and short vowels are lengthened by some 25 msec when followed by medial voiced obstruents. The present study investigated whether this vowel length cue influenced listeners when hearing stimuli with ambiguous vowel duration in an identical, neutralized consonantal context in which the underlying representation of the obstruent following the vowel differed in voicing. A vowel length continuum ([at] to [a:t]) was created and appended to initial consonants to make two pairs of real words. Each pair differed in vowel length with opposite underlying final consonant representations: /zat/-/za:d/, and /stad/-/sta:t/. Our question was whether the vowel category boundaries would be different in pairs like /zat/-/za:d/ as compared to /stad/-/sta:t/. Although the underlying consonant is either voiced or voiceless, the surface word-final consonant for both pairs of stimuli is always voiceless ([t]). If the listener uses a surface representation with a voiceless consonant to recognize the words, there should be no difference in categorization of the vowel-length continua. The results of a vowel categorization task, however, showed a significant difference in the location of the phoneme boundaries between the two continua, suggesting that listeners' perception seems to be guided by the underlying phonological representation of words. PMID- 1287385 TI - Acoustic and aerodynamic effects of interarticulator timing in voiceless consonants. AB - Interarticulator timing is a mechanism for producing linguistic contrasts that is widely used in different languages. This paper explores acoustic and aerodynamic effects of variations in laryngeal-oral coordination in voiceless consonants. Measurements of voice onset time and interarticulator phasing for individual tokens of stop consonants show weak correlations, indicating that interarticulator timing is only one factor determining voice onset time. Other factors most likely involved are glottal opening, transglottal pressure and air flow, and vocal fold tension. Taken together, these observations suggest that speakers may only have limited control of voice onset time. This could explain why languages do not seem to make fine-grain use of VOT for linguistic contrasts. Measurements of peak and minimum air flow during individual source pulses, obtained by inverse-filtering oral flow, show a pattern of decrease and increase in vowels following voiceless consonants. Subtle differences in the time course of these patterns occur following different consonants, suggesting that interarticulator phasing may be partly responsible for them. Closer examination reveals consistent correlations with interarticulator phasing for one speaker but inconsistent results for another. The results are discussed in terms of speech motor control and controlled variables in speech. PMID- 1287386 TI - Context effects in a double-weak theory of speech perception. AB - The present study provides an elaboration of the "double-weak" theory of speech perception proposed by Nearey (1990, 1991). In this framework, the objects of speech perception (and production) are viewed as neither primarily auditory nor primarily gestural; rather, they are abstract, symbolic elements lawfully constrained to map onto relatively simple (but not entirely transparent) patterns in both domains. Speech cannot be understood unless both articulation and acoustics are considered: Many production strategies appear to be directed at achieving acoustically-oriented goals, yet most context effects in speech perception seem to be motivated by the consequences of gestural overlap. The double-weak framework suggests that speech perception and speech production are less-than-perfect inverses of each other. Despite long-term accommodation of each for the demands of the other, real-time production and perception may operate as autonomous subsystems. A family of perceptual models is discussed that provides varying degrees of approximation to "ideal solutions" (in the sense of minimizing error rate) to classifying production data exhibiting contextual interactions. Members of this family that provide substantial, yet incomplete, compensation for the consequences of gestural overlap appear to be adequate to account for the results of many speech perception experiments. Such partial perceptual compensation allows, in principle, for the kind of imperfect "error correction" discussed by Ohala (1981, 1990) in conjunction with hypo- and hypercorrection phenomena. PMID- 1287387 TI - Perception and production of voiceless Spanish fricatives by Chicano children and adults. AB - In studying language change, Ohala and Lorentz (1977) observed that when the labial-velar glide [w] occurs adjacent to fricative noise, the resulting complex of acoustic features is most often perceived and pronounced as a labial, rather than a velar consonant. However, contemporary Spanish, as spoken in Mexico and the U.S. Southwest, presents a somewhat different pattern. The current research examined two directional predictions based on Ohala and Lorentz (1977) with reference to the perception and production of Spanish fricatives by Chicano children and adults: A Differential Effect of Context hypothesis (more labial/velar fricative interchanges will occur before rounded, rather than unrounded vowels or glides), and a Labial Predominance hypothesis (before a following rounded vowel or glide, labial fricatives will be favored in labial/velar interchanges). Results of perceptual tests provided support for these acoustically-based predictions, but subjects' productions also showed strong influence from sociolinguistic factors in the opposite direction. PMID- 1287388 TI - Phonetic features in young children's slips of the tongue. AB - The form in which phonological information is stored in the lexical entries of young children, and how this form changes over time, are questions which are difficult to address, given the limitations of current methodologies. However, slips of the tongue made by young children can be used to shed some light on the question. Earlier research (Stemberger, 1989; Jaeger, 1992) has shown that children as young as 1;7 (one year seven months) make slips in which single consonants or single vowels are substituted or exchanged, implying segmental organization in phonological representations. In the present paper, a corpus of 366 consonant substitutions and reversals made by young children, aged 1;7-6;0, are subjected to a multidimensional scaling analysis, and are shown to be governed by patterns of phonetic similarity, indicating that these segments have phonetic structure. A feature system based on the scaling procedure is found to be somewhat different from one generated by van den Broecke and Goldstein (1980) from adult errors, especially in manner features. While both adults and children err on the 'place of articulation' feature most often, and 'nasality' least often, children produce 'voicing' feature errors less often than adults do, indicating that voicing may be a more important organizing principle for young children than for adults. Some age-related trends in number and type of feature errors are discussed. PMID- 1287389 TI - A performance constraint on compensatory lengthening in child phonology. AB - The systematic mispronunciations of young children often resemble phonological rules, and there is a temptation to treat the data as identical to adult phonological data. However, performance factors are often evident in the child's speech. Constraints in phonological theory are "hard" (all-or-nothing), but constraints in performance are often "soft" (allowing something to occur under some conditions but not under others). One child phonological process that has an obvious linguistic interpretation is compensatory lengthening, wherein a segment becomes long when a nearby segment is deleted. In data from one child, two compensatory lengthening processes led to the creation of [i:] but never [u:], even though [u:] appeared in the child's speech as the correct realization of adult /u:/. The child also showed later mastery of all back rounded vowels and glides than of the corresponding front vowels and glides. It is argued that compensatory lengthening never led to [u:] because of a soft performance constraint against back rounded segments; the hard constraints of phonological theory cannot account for such effects. Performance must be taken into account in the description of child phonology data. PMID- 1287390 TI - A commercial large-vocabulary discrete speech recognition system: DragonDictate. AB - DragonDictate is currently the only commercially available general-purpose, large vocabulary speech recognition system. It uses discrete speech and is speaker dependent, adapting to the speaker's voice and language model with every word. Its acoustic adaptability is based in a three-level phonology and a stochastic model of production. The phonological levels are phonemes, augmented triphones (phonemes-in-context or PICs), and steady-state spectral slices that are concatenated to approximate the spectra of these PICs (phonetic elements or PELs) and thus of words. Production is treated as a hidden Markov process, which the recognizer has to identify from its output, the spoken word. Findings of practical value to speech recognition are presented from research on six European languages. PMID- 1287391 TI - The interaction of coarticulation and prosody in sound change. AB - Ohala (1974, 1981a) has proposed that sound changes can originate in hearers' misinterpretations of synchronic phonetic patterns. This paper applies this idea to sound changes that are conditioned by the prosodic environment, such as the voicing of voiceless fricatives in unstressed syllables in Proto-Germanic. Browman and Goldstein's (1989, 1990) "gestural score" suggests a representation of synchronic patterns in which extreme overlap between gestures of neighboring phoneme segments in casual speech can produce the appearance of a feature change or a segment deletion. Many of the sound changes that are conditioned by prosodic environment can be viewed as a diachronic reinterpretation of just such synchronic fast-speech processes. For example, vowel reduction in unstressed syllables can be viewed as a reinterpretation of undershoot that occurs when the vowel is overlapped to a great extent by the oral gestures for neighboring consonants. Phonetic data are reviewed that support analogous accounts of stop spirantization, voiceless obstruent voicing, and even the insertion of an intrusive stop in clusters such as /ns/ in some prosodic environments. PMID- 1287392 TI - On the role of perception in shaping phonological assimilation rules. AB - Assimilation of nasals to the place of articulation of following consonants is a common and natural process among the world's languages. Recent phonological theory attributes this naturalness to the postulated geometry of articulatory features and the notion of spreading (McCarthy, 1988). Others view assimilation as a result of perception (Ohala, 1990), or as perceptually tolerated articulatory simplification (Kohler, 1990). Kohler notes that certain consonant classes (such as nasals and stops) are more likely than other classes (such as fricatives) to undergo place assimilation to a following consonant. To explain this pattern, he proposes that assimilation tends not to occur when the members of a consonant class are relatively distinctive perceptually, such that their articulatory reduction would be particularly salient. This explanation, of course, presupposes that the stops and nasals which undergo place assimilation are less distinctive than fricatives, which tend not to assimilate. We report experimental results that confirm Kohler's perceptual assumption: In the context of a following word initial stop, fricatives were less confusable than nasals or unreleased stops. We conclude, in agreement with Ohala and Kohler, that perceptual factors are likely to shape phonological assimilation rules. PMID- 1287393 TI - An acoustical basis for universal phonotactic constraints. AB - Spectral characteristics of some selected phoneme sequences are investigated in an attempt to explain cross-linguistic tendencies in phonotactic constraints. A hypothesis is offered that some universal sequential constraints are acoustically motivated. Two acoustic factors are posited as determinants of favored/disfavored sequences: The magnitude of acoustic modulation within a sequence and the degree of acoustic difference between sequences. The hypothesis is tested experimentally for its applicability to some of the universal constraints. Trajectories of the first three formants are obtained for selected sequences of stop + liquid + vowel, stop + glide + vowel, stop + vowel, and vowel + stop. Standard Euclidean distance in frequency is computed as a measure approximating each acoustic factor. The results show that some universally rare or unstable phoneme sequences can be explained on the basis of their lack of spectral modulation and/or their spectral similarity to other sequences, suggesting that acoustic/auditory factors play a significant role in determining the phonetic shape of language. PMID- 1287394 TI - Fundamental frequency as an acoustic cue to accent perception. AB - It is generally recognized that the most significant cue to accent location is fundamental frequency (F0) in both Japanese and English. Furthermore, it is widely believed that a syllable is perceived as accented if the syllable contains an F0 peak. However, Sugito (1972) found that, in Japanese, if an F0 peak is followed by a steep F0 fall, the syllable preceding the F0 peak may be perceived as accented. In this article we present two experiments which investigate the relationship between F0 peak and F0 fall rate in accent perception for Japanese and English. The first experiment confirms that, for Japanese, both F0 peak location and F0 fall rate affect listeners' judgements of accent location. Specifically, the later the F0 peak occurs in a given syllable, relative to the syllable boundary, the greater the F0 fall rate necessary for listeners to perceive the preceding syllable as accented. The second experiment shows that this phenomenon is not unique to Japanese: Perception of accent location in English is also influenced by both F0 peak location and post-peak F0 fall rate. PMID- 1287395 TI - The phonetics and phonology of perceptually motivated articulatory covariation. AB - This paper presents evidence that the acoustic effects of demonstrably independent articulations are integrated in the perception of vowel height and [voice] contrasts. This evidence supports two hypotheses: That, in at least some instances, articulatory covariation is perceptually motivated, and that the objects of speech perception are auditory rather than articulatory. Furthermore, it appears that perceptual integration can either increase or decrease the distinctiveness of contrasting speech sounds, so it may not only create favored patterns of articulatory covariation but also disfavored patterns. This suggests that integration is a product of general auditory mechanisms, not of mechanisms specific to speech perception. PMID- 1287396 TI - HLA and disease. AB - Many human diseases are associated with HLA class I, class II and class III antigens. It appears that the class III antigen disease associations can be explained by a direct defect operating at the level of either the class III gene or its gene product. The mechanism underlying class I and class II antigen disease associations is at present unknown. In this review we have considered thirty diseases which have been ranked according to their relative risk as defined by the frequency of a given HLA antigen in patient and control populations. The chronic inflammatory disorder, ankylosing spondylitis and its association with HLA B27 has been used as a model to study the HLA linked diseases. We have suggested that the disease may be caused by the Gram-negative microorganism Klebsiella which has antigenic similarity to HLA B27. It is proposed that some antibodies made against Klebsiella bind to HLA B27, thereby acting as autoantibodies leading to the pathological sequelae of chronic inflammatory arthritis. This is the crosstolerance hypothesis or molecular mimicry model and it has been compared to the receptor model. It is further suggested that the crosstolerance hypothesis can be utilised as a general theory to explain the association of other diseases with the class I and class II antigens, and offer a possible explanation for the polymorphism of HLA. PMID- 1287397 TI - Making dentistry more affordable. PMID- 1287398 TI - Amalgam: a proven restorative material. PMID- 1287399 TI - Simplified fixed prosthetics on Branemark fixtures. PMID- 1287400 TI - Improving the performance of the office sterilizer. PMID- 1287401 TI - Reversal of drug resistance in Mycobacterium leprae by ampicillin/sulbactam. AB - The multiplication of Mycobacterium leprae in foot pads of experimentally infected mice was suppressed by intramuscular administration of ampicillin combined with sulbactam or YTR-830H, two potent inhibitors of beta-lactamase in the bacteria. The antibiotic or the inhibitors by themselves were inactive. Ampicillin/sulbactam also inhibited the growth of drug-resistant M. leprae which grew in the presence of rifampin or dapsone. The finding provides a new approach to treat leprosy and to overcome drug resistance of the mycobacteria. PMID- 1287402 TI - Changes with time in the oral microflora and dental caries induction in hyposalivated rats fed on sucrose diet. AB - The effects of hyposalivation on the induction of dental caries and the change in oral microflora were examined at weekly intervals in Sprague-Dawley rats fed on diet 2000 containing 56% sucrose. In hyposalivated rats, significant dental caries was induced within one week and its severity increased with the experimental period. Bacteriological examinations demonstrated that the number of total cultivable microorganisms, lactobacilli and Staphylococcus aureus increased significantly shortly after surgical induction of hyposalivation, while the number of streptococci and yeasts did not increase significantly until the 7th week, beyond which time remarkable gross caries developed. A positive correlation was found between the caries score and the recovery of lactobacilli from mandibles of hyposalivated rats, while there was no statistically significant correlation between the caries score and the recoveries of S. aureus. On the other hand, dental caries was not induced in control rats fed on sucrose diet with no surgically-induced hyposalivation. It was also found that the number of lactobacilli increased significantly shortly after diet 2000 was given to control rats, but S. aureus was rarely recovered from the mandibles of control rats throughout the experiments. The roles of lactobacilli and S. aureus in the induction of dental caries under the hyposalivated condition were discussed and it was suggested that lactobacilli may play some significant role in the induction of dental caries in hyposalivated rats. PMID- 1287403 TI - An improved method for the serotyping of free coagulase from Staphylococcus aureus. AB - The serotyping of free coagulase, one of the most reliable ways to identify strains of Staphylococcus aureus, and widely employed in Japan, has been improved by adding magnetite sand to the reaction mixture. Culture medium supernatant and a type-specific antibody are mixed in a well of a microtiter plate, and plasma enriched bovine fibrinogen is treated with magnetite sand. The use of tranexamic acid and gum arabic in the reaction mixture also increases the sensitivity of the reaction. Finally, the plate is placed on a magnetic stirrer. If the type of the coagulase corresponds to that of the antibody, no clot formation will occur, and this is easily confirmed by the movement of the sand. Although the amount of reaction mixture required is much less than that for the conventional tube method, our new method is able to detect slight increases in viscosity of the reaction mixture due to fibrin formation even before complete clotting occurs, thus providing very high sensitivity. Clot formation can also be judged by observing a turbid mass of fibrin in the well (Hwang's method), but this approach is a little slower than our method involving immobilization of magnetite sand. PMID- 1287404 TI - Suppression of cell-mediated immunity by street rabies virus infection. AB - An attempt to define a severe suppression of cell-mediated immunity by street rabies virus infection was undertaken by using the mice lethally and peripherally infected with a street rabies virus (1088 strain). The cell-mediated cytotoxic (CMC) activity of the spleen cells from those mice once slightly increased until day 4 after infection but declined rapidly thereafter until their death on days 10 to 12 after infection. In parallel with a decrease of CMC response of the spleen cells from 1088-infected mice, proliferative response to Con A, IL-2 activity in the culture supernatants of Con A-induced proliferation, responsiveness to exogenously added IL-2 and to Con A to express IL-2R, of those cells became suppressed, and the marked decrease of the total number of spleen cells was observed. Selective depletion of CD4+ and CD8+ cells in the spleens, abnormalities of IL-1 and E-type prostaglandins (PGE2) production or production of inhibitory component able to block IL-2 activity by spleen cells were not observed and these factors did not appear to be associated with the suppression of proliferative response to Con A. However, an apparent association of CD8+ cells in the suppression of differentiation of pre-cytotoxic lymphocytes (CTL) into CTL was demonstrated in the co-culture experiments of the spleen cells from 1088-infected mice with spleen cells of mice infected with an attenuated rabies virus (ERA strain) which can induce higher levels of CMC response. There was no evidence of the productive replication of rabies virus in thymus and spleen of 1088-infected mice. The relationship of these observations to current theories on virus-induced immunosuppression was discussed. PMID- 1287405 TI - Establishment of stable cell lines producing anti-Pseudomonas aeruginosa monoclonal antibodies and their protective effects for the infection in mice. AB - Human-human hybridomas producing monoclonal antibodies (MoAbs) specific for five major serotypes of Pseudomonas aeruginosa were developed by fusing P. aeruginosa primed and Epstein-Barr virus-transformed cells with human myeloma P109 cells using polyethyleneglycol. The MoAbs which were produced by the hybridomas were protective against lethal intraperitoneal (i.p.) challenge of P. aeruginosa (10 LD50) in mice. The 50% effective dose (ED50) values of MoAbs ranged from 0.5 to 10.2 micrograms/mouse and were 26 to 240 times more protective than a commercial human IgG preparation. MoAb administration to mice promoted bacterial clearance in peritoneal cavity, and prevented bacterial invasion into blood in the way of increasing both the number of bacteria trapped by a macrophage and the ratio of macrophages that trapped bacteria. MoAbs also showed protective effects against lethal infection of P. aeruginosa in the mice which were decreased in polymorphonuclear cells (PMN) by cyclophosphamide (CY). All MoAbs showed serotype specific binding to the clinical isolates of P. aeruginosa as well as to the immunized strains. The hybridoma cell lines maintained their capacity to produce MoAb continuously for more than 12 months and produced 10 to 60 micrograms MoAbs per 10(6) cells in 24 hr. It is practicable to use these cell lines for large scale production of anti-P. aeruginosa MoAbs and such MoAbs must be useful for the therapeutics of patients with P. aeruginosa infection. PMID- 1287406 TI - [Role of phenylalanine in the biosynthesis of fluorescent pigment in Pseudomonas putida bacteria]. AB - The contemporary data of the participation of phenylalanine in the biosynthesis of fluorescent pigment pyoverdine PM of Pseudomonas putida strain M are presented. Using aro1phu1 mutant of this strain, it has been shown that one of the precursors of the dihydroxyquinoline moiety of the pyoverdine PM is phenylalanine in the D- or L-form. These results were confirmed in experiments with 14C-phenylalanine incorporation. Pyoverdine PM that was synthesized by aro1phu1 mutant from exogenous phenylalanine is identical with the pigment from wild type cells. PMID- 1287407 TI - [Regulation of the expression of plasmid determination responsible for caprolactam degradation by bacteria of the genus Pseudomonas]. AB - On the basis of the study of some Tn5 induced mutants in Pseudomonas putida strain BS836 containing the plasmid pBS268 coding caprolactam degradation, growth on caprolactam and its intermediates, and the data on the induction of oxidative activities in plasmid containing P. putida strain BS831 it was shown that plasmid and chromosome genes regulated the expression of CAP-determinants. The regulation has some elements of the negative control mechanism. Caprolactam is the inducer of the synthesis of key enzymes cleaving it and its intermediates (aminocaproic and adipic acids). At the same time each of its intermediates induced the synthesis of enzymes responsible for its cleavage. PMID- 1287408 TI - [Extracellular amino acids of aerobic spore-forming bacteria]. AB - An ability to synthesize and accumulate in the growth medium for extracellular amino acids of 108 strains of 13 aerobic sporeforming bacteria species at deep cultivation on the simple synthetic glucose-mineral liquid nutrient medium optimized for the representatives of this genus. Has been studied the bacillus strains studied in the present conditions synthesize 19 amino acids and 2 amino carbons in different quantities and combinations. Amino acids being synthesized the most and least by these microorganisms have been determined in quantitative expression. Extracellular amino acid accumulation was proved to be a strain property not of genus. In general, the genus studied was evaluated as active one in amino acid production. The most active strains may present an interest as initials for further selective obtaining of producers of separate amino acids. The outlook for aerobic bacilli strains having marked amino-synthesizing properties and complex of other biological activities is being discussed for construction of medicinal and prophylactic of live microbial culture preparations. PMID- 1287409 TI - [Study of asynchronous and synchronous yeast cultures using flow cytofluorometry]. AB - Distribution of Saccharomyces cerevisiae, Candida boidinii and Candida tropicalis cells according to DNA content was investigated using laser flow cytofluorometry. Cells distribution curves according to DNA content possessed two maxima in case the sample belonged to the exponential phase of the asynchronous batch culture, or one maximum in case the sample was from the stationary phase of growth. In synchronous cultures variations of cells distribution curves according to DNA content (age structure of the population) were demonstrated and the curves with one maximum and plateau were observed. PMID- 1287410 TI - Self-aggregation of squid cranial cartilage proteoglycans. AB - Squid cranial cartilage has been found to contain three different proteoglycan populations, two of which form aggregates (Vynios, D.H. and Tsiganos, C. P., Biochim. Biophys. Acta 1033: 139-147, 1990). The aggregation involves interaction of their protein cores as assessed by electron microscopy and biochemical data. Aggregating oligopeptides were isolated after mild trypsin digestion which inhibited self-aggregation of proteoglycans. The aggregation does not involve interaction of the side chains of polar amino acids and evidence is provided that it is mediated through hydrophobic interaction. It is enhanced upon concentration or incubation of the samples at 37 degrees C. PMID- 1287411 TI - Synthesis of low buoyant density proteoglycans by human chondrocytes in culture. AB - Human chondrocyte strains were derived from explant outgrowth of nonarthritic or osteoarthritic human cartilage. Chondrocytes radiolabeled with [35SO4] or [35S] methionine were used to measure the biosynthesis of proteoglycans recovered from the most buoyant fraction (A4) of a CsCl density gradient centrifugation performed under associative conditions. The proteoglycans isolated from the A4 fraction (rho < 1.47 g/ml) were hydrodynamically small and contained both large and small glycosaminoglycan chains. When assessed by SDS/PAGE using 3-16% gradient gels, two subpopulations of small proteoglycans (smPG) were identified. The larger of the two species (smPG-I) migrated slower than the 200 kDa marker protein; when reassessed on 3-5% acrylamide gels, its apparent molecular mass was larger than the 480 kDa and 440 kDa alpha and beta heavy chains of dynein. We estimated the apparent molecular size of this smPG to be approximately 520 kDa. The smaller smPG (smPG-II) had an apparent average molecular mass of 180 kDa (range 170-210 kDa) after 3-16% SDS/PAGE. Three monoclonal antibodies, 1C6, 5D4, and S103L, reactive with the hyaluronic acid binding region of the aggregating proteoglycan core protein, keratan sulfate, and a core protein domain in the chondroitin sulfate attachment region, respectively, reacted with a single protein (apparent molecular mass, 180 kDa) that was similar in size to smPG-II. PMID- 1287412 TI - Verapamil decreases cyclic load-induced calcium incorporation in ROS 17/2.8 osteosarcoma cell cultures. AB - Bone is a tissue that responds to mechanical load by changing its internal architecture. However, the mode of transmission of mechanical stimuli into biological signals and the effect of load at the cellular level are still not clear. An in vitro system, a Flexercell Strain Unit, was used to apply cyclic load to osteoblast-like cells in culture. In the first series of experiments, ROS 17/2.8 rat osteosarcoma cells, cultured on Flex I, flexible bottomed culture plates, were subjected to a 0.05 Hz, 0.24 STRAIN cyclic load regime for 3 and 7 days, in vitro. One group subjected to load received verapamil, a calcium channel blocker, throughout the experimental period. A second group was exposed to load but received no verapamil. A third group had no drug or load and a fourth group had no load but received verapamil. Cultures were incubated for 24 hours prior to collection with 10 microCi of 45CaCl in the medium, then well bottoms were divided to yield outer (maximum) and inner (minimum) load zones for assay of radioactivity. The effect of verapamil during a 7-day loading period was studied by adding the drug to individual cultures at daily intervals. Results indicated that mechanical loading stimulates calcium incorporation in ROS 17/2.8 cell cultures by day 7 but not by day 3. Only early verapamil addition decreased load induced calcium incorporation when drug was added prior to day 4. If verapamil was added after 4 days, the channel blocker did not diminish load-induced calcium incorporation. PMID- 1287413 TI - Demonstration of type III collagen in the dentin of mice. AB - It has been reported that, although type III collagen is present in human dentin where there is dentinogenesis imperfecta and in reparative dentin, it is absent in normal dentin. In a preliminary study, however, we observed evidence showing that small amounts of fibers showing positive labeling for type III collagen are present in the molars of normal mice. In the present study, in order to localize type III in normal dentin, immunofluorescent and immunoelectron microscopic examinations of the molars of normal mice were carried out using affinity purified antibodies to mouse type III and type I collagen. The fibers positive for type III collagen were much more frequently observed in the root than in the crown. These fibers ran in peritubular dentin or near that in parallel to them. The incidence of the existence of dentinal tubules associated with type III collagen-positive fibrils either in or near peritubular dentin was low. These fibrils positive for type III collagen showed a clear cross-banding. In dentinal tubules, unusual collagen aggregations, segment long-spacing-like and fibrous long-spacing-like structures which were intensively stained for type I collagen but weakly so for type III collagen were seldom observed. Type III collagen positive fibers often extended towards the pulp beyond the odontoblast layer, suggesting that these fibers were produced, at least partly, by the pulp cells. PMID- 1287414 TI - The serine proteinase inhibitory proteins of the human intervertebral disc: their isolation, characterization and variation with ageing and degeneration. AB - Serine proteinase inhibitory proteins (SPIs) were extracted from human disc tissues using 2 M GuHCl and subjected to CsCl density gradient ultracentrifugation. The SPIs recovered in the low buoyant density fractions (rho < or = 1.35 g/ml) were purified by a combination of gel-permeation, ion-exchange, trypsin affinity, and reverse-phase high performance chromatographies. Characterisation of the major disc SPI by polyacrylamide gel electrophoresis, isoelectric focussing, enzyme inhibition and pH stability studies indicated that this small molecular weight (12-14 kDa), highly basic (pI > 9.5), acid-stable but alkaline-labile protein possessed potent inhibitory activity against bovine pancreatic trypsin and chymotrypsin, and human leukocyte elastase and cathepsin G. Two-major and two-minor low molecular weight cationic SPI species were identified by reverse-phase HPLC. The predominant species was identical to a human articular cartilage SPI sharing amino terminal sequence homology with the mucus proteinase inhibitors (MPIs). It also cross-reacted with an antiserum to the MPIs and behaved identically to secretory leucocyte proteinase inhibitor (SLPI) when examined by reverse phase HPLC, and SDS PAGE. A higher molecular weight (54 kDa), anionic (pI approximately 4.6) SPI was also purified and identified as alpha 1-proteinase inhibitor (alpha 1-PI). Quantification of alpha 1-PI and the small molecular weight cationic disc inhibitors indicated that the latter were depleted in morphologically degenerate disc tissues while levels of alpha 1-PI were somewhat higher although a large proportion of the alpha 1-PI was inactive. A depletion of total SPI levels was evident overall in degenerate discs suggesting a functional role for these inhibitory proteins in the maintenance of IVD matrix homeostasis. PMID- 1287415 TI - Interleukin-6 does not regulate interstitial collagenase, stromelysin and tissue inhibitor of metalloproteinases synthesis by cultured human fibroblasts. AB - We have examined the effect of interleukin-6 (IL-6) on the synthesis of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) by human skin fibroblasts, both at protein and messenger RNA levels. IL-6 did not modulate the production of MMPs and TIMP. Furthermore IL-6 did not modify the stimulatory effect exerted by interleukin-1 (IL-1) on the expression of MMPs and TIMP. These results strongly suggest that IL-6 is not involved in the extracellular matrix breakdown, either directly by acting on cell production of MMPs or TIMP, or indirectly by modulating the effect of IL-1 on the synthesis of MMPs and TIMP. PMID- 1287416 TI - Monoclonal antibodies against human fibroblast collagenase and the design of an enzyme-linked immunosorbent assay to measure total collagenase. AB - Monoclonal antibodies have been raised against purified human fibroblast collagenase and characterised. One of these antibodies has been used in combination with a polyclonal anticollagenase antibody in a double antibody sandwich ELISA to measure collagenase. The assay range was 2-50 ng/ml collagenase. The assay measures total collagenase, i.e. pro- and active enzyme as well as collagenase in complex with TIMP. The level of collagenase has been measured in sera samples from patients with rheumatoid arthritis and compared with age- and sex-matched controls. The levels measured were: rheumatoid arthritis, 69 +/- 29 ng/ml; normal, 49 +/- 14 ng/ml. PMID- 1287417 TI - Dissociation of collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex--its application for the independent measurements of TIMP-1 and collagenase activity in crude culture media and body fluids. AB - Collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex was prepared from activated collagenase and TIMP-1 purified from culture media of human skin fibroblasts. After having been confirmed to be a complex by zinc chelate chromatography, the complex was demonstrated to dissociate by passage through an anti-TIMP-1 monoclonal antibody-affinity column. On the basis of above evidence, a simple strategy was set up for the independent measurements of TIMP-1 concentration, and both active and total collagenase activities in crude culture media and body fluids. PMID- 1287419 TI - In vivo neutralization of tumor necrosis factor-alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica infection in mice. AB - Cytokines are important mediators of the inflammatory host response against infectious agents. In this study, the role of tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN-gamma) in the elimination of a primary infection with highly virulent Yersinia enterocolitica serotype 0:8 strain WA-P has been investigated in C57BL/6 mice. The injection of anti-TNF-alpha or anti-IFN-gamma antibodies ("serotherapy") prior to the intravenous challenge of a sublethal dose of Y. enterocolitica caused an increased bacterial net-growth in the spleens, although this effect was more pronounced for anti-TNF-alpha treatment. The later treatment with anti-TNF-alpha or anti-IFN-gamma antibodies on day 3 post infection likewise abrogated resistance to Y. enterocolitica and, subsequently, led to death from progressive infection. Our data demonstrate for the first time that the endogenous production of both the cytokines TNF-alpha and IFN-gamma is required for the restriction of a primary Y. enterocolitica infection in mice. PMID- 1287418 TI - Bacterial transferrin receptors--structure, function and contribution to virulence. PMID- 1287420 TI - Determination of IgG subclass antibodies to Pseudomonas aeruginosa outer membrane proteins in cystic fibrosis lung infection using immunoblotting and enzyme-linked immunosorbent assay. AB - IgG subclass antibodies to Pseudomonas aeruginosa outer membrane proteins (OMP) were investigated in serum from cystic fibrosis (CF) patients by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Fifteen patients (eight in good and seven in poor clinical condition) have been followed for an average of 13 years with multiple serum samples covering the preinfection, and early and late stages of chronic infection. Laser-scanning densitometry of photographs taken from immunoblots was used to quantify antibody level and compare with ELISA titres. The earliest anti-OMP antibodies to appear were of the IgG1 subclass. There was no significant difference in IgG subclass antibody levels to OMPs between patients in relatively good and poor clinical condition. Data presented indicate a high positive correlation among measurements of IgG subclass antibodies to P. aeruginosa OMPs using ELISA and immunoblotting. PMID- 1287421 TI - Lack of activity of transferrins towards Streptococcus spp. AB - Clinically relevant Streptococcus spp. were tested for their susceptibility towards human serum transferrin (TR) and lactoferrin (LF). Neither clinical isolates or type strains were inhibited by transferrins (5 mg/ml). All species tested were shown to be able to grow under iron-limiting conditions (< 0.1 microM) and this might account for the lack of TR or LF activity towards streptococci. Even if not sensitive to LF and TR, some species were shown to bind LF in the apo-form. PMID- 1287422 TI - [Results and experiences of transvenous endocardial defibrillator therapy]. AB - We studied the follow-up of 72 patients who underwent implantation of a transvenous defibrillation lead system (ELS) (Endotak, CPI). All patients had ventricular tachycardia (VT) or fibrillation (VF) refractory to antiarrhythmic drug therapy. There were 51 patients with coronary disease and 21 patients had non-ischemic VT/VF. ELS was combined with a subcutaneous patch in 52 patients and implanted alone ("single lead only") in 20 patients. 40 patients received the ELS combined with antitachycardia pacing devices (Ventak PRx, CPI; Cadence, Ventritex) and 32 patients with the Ventak P 1600 or P2, CPI. Implantation of the ELS was attempted in 80 patients and performed in 72 patients (90%): Intraoperatively, the mean defibrillation threshold (DTF) was > 25 Joule (J) in five patients and no reliable ELS position was possible to achieve in three patients. These eight patients underwent thoracotomy with epicardial patch implantation. The mean DFT was < or = 20 J in all 72 patients with a mean DFT of 14 +/- 8 J in VT patients and 17 +/- 10 J in VF patients. Two of 80 patients (3%) died: one patient died intraoperatively and one during the mean follow-up of 6 +/ 2 (< 1 to 18) months. Complications occurred in three patients (4%): Dislocation of the Endotak electrode was observed in two patients (3%) and one patient developed pneumothorax postoperatively. Our data show that the ELS is most suitable in the majority of patients with VT/VF and is the approach of first choice for cardioverter defibrillator implantation at the present time. However, despite a relatively low intra- and perioperative complication rate, this approach should not be performed in institutions without cardiac surgery. PMID- 1287423 TI - [The role of human atrial natriuretic peptide on pathogenesis of nephropathy in patients with type I diabetes mellitus]. AB - Divergent findings in recent clinical and experimental studies have caused considerable controversy as to whether or how elevated plasma levels of human atrial natriuretic peptide (hANP) may contribute to the pathogenesis of diabetic nephropathy in type I diabetic patients. Therefore, we decided to examine potential changes of urinary albumin excretion (UAE), urinary excretion of alpha 1-microglobulin (A-1-M), mean arterial blood pressure (MAP), hANP levels, creatinine clearance and HbA1 in the course of a prospective one-year study in 19 patients (13 females, six males, age 29 +/- 2 years). All patients had intensified insulin treatment. Seven patients at increased risk for eventually developing nephropathy (group 1) were identified by repeatedly showing elevated UAE ( > 30 mg/24 h). The other patients served as controls (group 2). Patients in group 1 differed from those in group 2 in increased A-1-M (maximal difference, 10.1 +/- 1.5 vs. 5.5 +/- 1.0 mg/l, p < 0.01). In the second half of the study, 43% of the MAP measurements in group 1 exceeded 100 mmHg in comparison to 19% in group 2 (p < 0.01). Simultaneously, 38% of the hANP levels in plasma in group 1 were higher than 25 pg/ml (upper limit of normal range) in comparison to 15% in group 2 (p < 0.05). There were no differences in creatinine clearance between both groups. 58% of the HbA1 concentrations measured in group 1 in the course of the study exceeded 8.5% in comparison to 47% in group 2 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287424 TI - [Upper intestinal endoscopy in 188 bronchial cancer patients and 118 breast cancer patients with abdominal symptoms. The GI Metastases Study Group]. AB - With the aim of analysing the pathological findings of upper gastrointestinal endoscopy in patients with bronchial or breast cancer and gastrointestinal symptoms a multicenter study was carried out over one year (1990) by 26 medical departments. One duodenal metastasis was verified among 188 patients with lung cancer. Seven of 118 patients with breast cancer developed symptomatic stenosis of the esophagus. A total of 42.9% of the patients with lung cancer and 38.6% of the patients with breast cancer had pathological findings detected by upper gastrointestinal endoscopy. Most frequent findings were duodenal and gastritic ulcers (lung cancer 15.0%, breast cancer 15.8%), esophagitis (lung cancer 16.3%, breast cancer 8.9%) and symptomatic stenosis of the esophagus (lung cancer 9.5%, breast cancer 7.0%). The authors conclude that there is a high frequency of relevant pathological upper gastrointestinal tract findings in symptomatic patients with breast or lung cancer, but that true metastatic disease is a rare phenomenon with the exception of metastatic involvement of the esophagus. PMID- 1287425 TI - [Traveler's diarrhea in Turkey. Prospective randomized therapeutic comparison of charcoal versus tannin albuminate/ethacridine lactate]. AB - In most cases traveler's diarrhea is a self-limiting disease not requiring professional assistance. As data on self-treatment are very limited, a prospective randomized trial was performed in 620 German tourists spending a two week-holiday in Turkey. 31.6% of these travelers developed diarrhea and 186 were assigned to two treatment groups, receiving either medical coal or a combination of tannalbuminate and ethacridinlactate (TA/EL). In the TA/EL group stool frequencies significantly earlier returned to normal and complaints of moderate to severe abdominal pain were recorded less frequently (50 vs. 82.2%) than in patients receiving charcoal preparations. Both medications were well tolerated and TA/EL appeared more efficient for self medication of uncomplicated traveler's diarrhea. PMID- 1287426 TI - [Bilateral lung infiltration with therapy-resistant fever]. PMID- 1287427 TI - [Update oncology '92. The age of meta-analysis]. PMID- 1287428 TI - [Macroscopic anatomy--a dispensable subject in preclinical education? Results of a survey of medical students at the end of their education]. PMID- 1287429 TI - [Non-puerperal granulomatous mastitis: sarcoidosis or nonspecific inflammatory reaction?]. PMID- 1287430 TI - [Herpes simplex virus infection in pregnancy: epidemiologic, diagnostic and therapeutic data. An unusual case of HSV-1 in monozygotic twins]. AB - The Authors report a case of two pre-term monocorial twins affected by HSV-1 infection (Herpes Simplex Virus type 1), with generalized sepsis and involvement of the central nervous system (CNS), born by mother with primary infection who presented a typical vesicular eruption a week before delivery. As the HSV-1 was a disseminated type and the CNS was involved in both the twins, the diagnosis was based on clinical and laboratory findings (specific IgM and IgG) and on the use of Delpech-Lichtblau antibody liquoral index, a significant results both in the first and the second twin. Intensive care and early specific treatment with Acyclovir allowed a slow but progressive improvement of the twins' clinical picture. The antibody liquoral index may therapy of the viral sepsis cases involving the CNS, more than the cultural or antigen isolation of the treated virus. PMID- 1287431 TI - [Evaluation of a pediatric emergency room: ten years later]. AB - Utilization of the pediatric Emergency Room has been evaluated during the year 1991, by a questionnaire study on 694 children. By comparison with a previous research in 1981 it was possible to identify a further decrease of urgent and appropriate visits with increase of those inappropriate. Visits were more frequently urgent of appropriate in case of acute health problems, inappropriate if related to recurrent problems. Without considering true emergencies, three main causes for ER consultation have been identified: family custom, inappropriate relationships with the practitioner, dependence on the hospital. In the first group of children most of the visits proved inappropriate. The study points out a further increase of inappropriate utilization of ER, due mainly to inappropriate relationships between the family and the practitioner. This has to be corrected to reduce costs and improve child care. PMID- 1287432 TI - [Ambulatory and day hospital: pediatrics without any time spent in hospital]. AB - The Authors show their six years' experience (1985-1990) in ambulatory activity and day hospital replacing the children's ward in a Lombard Hospital in order to prove the real efficaciousness of the formula "pediatrics without any time spent in hospital". They purpose a nosological framing of the services done in ambulatory and in hospital; they point out the indications for a really favourable use of the day hospital, they report the pathology treated in ambulatory (13,615 examinations) and in day hospital (1,632 admissions to hospital). After six years' experience, the Authors say that "Pediatrics without any time spent in hospital" can really meet most of the sanitary demands of the pediatric population and it is an instrument really improving and not reducing the treatment of the child. PMID- 1287433 TI - [Ureteric peristalsis in congenital vesico-ureteral pathology. Integrated sonographic and scintigraphic studies]. AB - Ureteric peristalsis is a key point for urinary progression. Its preoperative evaluation is important to assess indications for surgery. The study of the distal ureter is possible by means of ultrasound. Renal scintigraphy allows for a complete study of urinary progression along the ureter. A combined ultrasound and 99mTc-MAG3 preoperative work-up, has been performed in 32 urinary tracts (16 children ranging in age between 45 days and 11 years). Urinary progression occurs whenever peristaltic contraction makes the ureter lumen unpatent. PMID- 1287434 TI - [Niemann-Pick disease type C in monozygotic twins]. AB - The Authors describe two monochorionic twins affected by Niemann-Pick disease type C with a clinical picture beginning in the neonatal age and with a progressive mental deterioration, loss of speech and spasticity started at 30 months. The importance of cultured skin fibroblasts is emphasized. The evidence of a defective intracellular cholesterol esterification is established as an intrinsic feature of Niemann-Pick disease type C. PMID- 1287435 TI - [Psychomotor management in the rehabilitation of patients with myopathy in infancy. Case studies]. AB - The salient features are described of the psychomotor treatment given to two sisters: SA aged 11 yrs 5 months and MGA aged 9 yrs 9 months both affected with aspecific congenital myopathy and under medical treatment since they were 3 months old. These two cases were selected as examples for the following reasons: (1) they may offer the opportunity to highlight what should be the focal objective of all treatment of myopathic children whatever the syndrome involved, namely to ensure that the children retain capacities required for normal social life as long as possible and to help them retain the essential physical capabilities required for everyday life; (2) because the slower course of this type of myopathy permits the gradual implementation of a diversified treatment protocol in the various social contexts (family, school, play groups) in which these patients are able to lead a life whose limitations are scarcely visible for a long time. Experience in the treatment of these two cases confirms that the role of Psychomotor Education in the treatment of myopathy cases is essentially that of teaching the child to be aware of and responsible for its own movements as the disease progresses, while showing it how touse all its available sensomotorial instruments to counteract its muscular inadequacies which progressively damage the child's body image. Psychomotor education also provides the child with the self-assurance it needs in order to retain its autonomy within the framework of a knowledgeable and motivated family. PMID- 1287436 TI - [Macleod's syndrome as a cause of recurrent pneumonia in a child]. AB - Macleod's syndrome is a rare cause of recurrent pneumonia in children. A case report is described and the diagnostic utility of chest roentgenogram and CAT is emphasized. PMID- 1287437 TI - [Effects of moderate maternal drinking on some neonatal parameters]. AB - A cross-sectional study was conducted on 2415 mother/newborn pairs, in order to evaluate the relationship between maternal alcohol consumption and birth weight. The results of this study are consistent with previous reports, that pointed out the casual relationship between maternal drinking during pregnancy, and reduction in birth weight. This reduction was evident only on the subset of smokers. A further stratification by the sex of newborn, showed a heavier effect on male newborns, who experienced a significant reduction of 6.2 grams in birth weight for each g of absolute alcohol consumed daily during pregnancy by mother. The findings of this study support the evidence of neonatal functional damages due to alcohol, even at very low doses. A strong increase of early jaundice were found among the outcome of exposed women (OD = 3.30; 95% CI 1.03-10.54). PMID- 1287438 TI - Nurse Education Tomorrow Conference 1991. An examination of selected current student nurse issues. AB - Clinical teaching has become increasingly complex and difficult for nursing instructors. Pressures for public accountability in nursing education and patient care, economic stresses, marked changes in the nursing curricula, and the growth of collective bargaining units have all complicated the task of educating student nurses. Traditional issues focusing on teaching strategies, academic and clinical evaluation concerns have been extensively researched. What are the current issues facing nurse educators? Our project aimed to identify some current student nurse issues in selected nursing programmes. Using a convenience sample, data were collected from the chairmen of nursing education in selected agencies. Analysis following the Fox and Diamond framework (1965) revealed recurring issues relating to mature students, stress and the clinical environment, and the mentor needs are a few of the issues discussed in this paper. PMID- 1287439 TI - Simulation: current status in nurse education. AB - This paper suggests that in the light of recent developments in nurse education a review of available teaching and evaluation strategies is required. It is further suggested that the use of simulation for both teaching and evaluation purposes has much potential which has as yet to be fully exploited in nurse education. PMID- 1287440 TI - Portfolios: an 'affective' assessment strategy? AB - The curriculum research and development work undertaken to facilitate the implementation of a portfolio assessment strategy, as an integral component of a Project 2000 course, is described. Many excellent assessment schemes have floundered at the point of being put in to use, thus the question of consultation, reflection and preparation needs to figure from the early stages in the scheme is to be successful. This should include in-service education for nurse and midwifery educators and preparation of students. The principle questions explored in the paper are: What educational values do portfolios have? Against what criteria should students make decisions in relation to content? Against what criteria are educators to assess portfolios? The issue of evaluation of portfolio schemes is likely to determine whether portfolios maintain the important place they have captured in the nursing and midwifery education imagination. Finally, it is argued that innovations, such as portfolios, should be seen as catalysts, as points of departure, rather than as things to be implemented. PMID- 1287441 TI - Self-evaluation in nursing students in Finland. AB - The article explores the self-evaluation in nursing students in clinical evaluation: the structure and topics in evaluation sessions and the student teacher relationships. The data were collected by means of non-participant observation: evaluation sessions of 81 (= n) students were observed in hospitals and health centres. The results indicated the rather passive role of nursing students in self-evaluation; teacher-dominated relationships were the most frequent in sessions. In future there is a need for a deeper analysis of the clinical evaluation. PMID- 1287442 TI - The use of learning contracts in the clinical area. AB - This paper examines the implementation and evaluation of learning contracts in the clinical area with a small group of RGN students who were 18 months into their programme. An action research approach was used with the researcher acting as participant observer. Data collection methods included questionnaire, students self-evaluation, nominal group evaluation and researchers notes. The results indicated that through using learning contracts the tutor can effectively facilitate learning in the clinical area. Data collected indicated that the students did benefit from the experience. An important aspect that was identified is the need for adequate preparation of all those involved. The paper concludes that, although there are limitations, contract learning is a useful and valuable strategy to use in the clinical area providing the tutor with an alternative model for clinical contact. PMID- 1287443 TI - Cooperation project in basic nursing education--the introduction of a new nursing education program in Tianjin, China. AB - Over the last few decades, traditional basic nursing education has taken place in nursing schools in China. In 1988, a new cooperation project for basic nursing education was tried between a Tianjin nursing school and several hospitals (Tianjin is one of the industrial cities in China). In this paper, an experiment in nursing education in Tianjin is described. In order to help readers to understand the Cooperation Project, the preparation courses are also described. Several advantages and disadvantages are discussed; some new proposals are also put forward at the end of the paper. PMID- 1287444 TI - Communication for nurses: implications for nurse education. AB - To prepare the student of nursing to meet the demands of caring for the individual or a community within a dynamic and multi-cultural society, it is important that the nurse and the client see the healing process as being a co operative venture. This co-operation relies on the growth of trust and confidence between interlocutors. Underpinning this is not only a sound clinical knowledge base but a sophisticated communication process at which individuals must be competent. The author argues that this competence is not automatic; it must be worked at and developed if the nurse is to be truly committed to the healing process. It is the responsibility of nurse educators to facilitate the growth and development of this competence in the students of today, if they are to be the nurses of tomorrow meeting new challenges. This paper examines some of the issues involved. PMID- 1287445 TI - Institutional restraints upon education reforms: the case of mental health nursing. AB - The purpose of this paper is to temper over-optimistic expectations about the degree to which Project 2000 training will improve the quality of psychiatric nursing care. The paper commences by citing evidence that, to date, psychiatric nurses have tended not to adopt therapeutic approaches towards their patients. Curricular innovations aimed at encouraging them to do so have had little effect. It is argued that the effects of the latest education reforms may be similarly compromised. The reasons for mental health nurses not engaging in therapeutic care are as much to do with the institutions they work in as with the training that they receive. As long as nurses feel that it is part of their role to maintain institutional order, their therapeutic role will be compromised; while the latter requires social proximity, the former demands social distance. Moreover, because it is informal, rather than formal, therapeutic interactions that patients value in their dealings with nurses, it is not clear that the sort of knowledge that Project 2000 curricula are designed to impart will be therapeutically effective. PMID- 1287446 TI - CD-ROM: towards a strategy for teaching and learning. AB - Compact Disc Read Only Memory (CD-ROM) represents an exciting innovation in nurse education yet paradoxically has a potential to induce disillusionment and frustration. Purchasers of systems may well find that their investment does not bring the benefits they had been lead to expect. CD-ROM systems have the capacity to generate huge quantities of data on an equally large number of nursing topics. Arguably this very capability ensures certain 'built-in' problems. The purpose of this articles is to provide nurse teachers with information about CD-ROM, to highlight the resource implications of CD-ROM use and to consider the relative merits of various teaching and learning methods. To be worthwhile, strategies developed must be part of an information retrieval skills programme. PMID- 1287447 TI - Interactive video: an analysis of its value to nurse education. AB - This paper attempts to explain the emerging technology of interactive video and examine its possible place in nursing education. A brief description of the media is given with an exploration of the educational theory and justification underlying its use. A range of approaches to the evaluation of the technology itself and software available are given, which examine advantages and disadvantages for individual learners and for an organisation considering investment in this area. The possible role of interactive video in nurse education is discussed and a recommendation given that nurse educators need to keep up-to-date with developments in this type of educational technology and develop software suitable for the needs of nurses, rather than having to use packages developed for other purposes which have limited application for nursing. PMID- 1287448 TI - Early diagnosis and treatment of diabetes insipidus in a newborn infant: a case study. PMID- 1287449 TI - ECMO accidents: a survey of the incidence of mechanical failure and user error during extracorporeal membrane oxygenation. PMID- 1287450 TI - How little you are! PMID- 1287451 TI - Disseminated intravascular coagulation in the neonate. PMID- 1287452 TI - A review of ventilation-perfusion relationships in the neonatal lung. Part II: Use of oxygenation indices to evaluate neonatal lung disease. PMID- 1287453 TI - Assessment of inspiratory effort. PMID- 1287454 TI - If NICU nurses wrote to "Miss Decorum" .... PMID- 1287455 TI - Computer applications for staff education, Part II. PMID- 1287456 TI - Heparin. PMID- 1287457 TI - Case presentation: ranula. PMID- 1287458 TI - Determining your educational satisfaction. PMID- 1287459 TI - [Vascular proliferation in the stroma of gastric cancer and its significance]. AB - To elucidate vascular characteristics in the stroma of gastric cancer, the morphological and immunohistochemical changes of vascular components were examined in 27 gastric cancers and 7 noncancer gastric tissues including 2 peptic ulcers. In differentiated adenocarcinoma, a large number of blood vessels were observed in vicinity of the cancer glands and type IV collagen (C-IV) was localized around the blood vessels and cancer glands, and ultrastructurally, cytoplasmic organelle and weibel-Palade bodies were encountered in the endothelium. In poorly differentiated adenocarcinoma, a small number of blood vessels were distributed sporadically in the stroma and there were vascular endothelia in which von Willebrand factor (VWF) was localized, and there were much more endothelia in which VWF was not localized compared with differentiated adenocarcinoma. C-IV was localized only around the blood vessels and OKM5 was localized in the endothelia which were distributed in the center of cancer nest in poorly differentiated adenocarcinoma. Ultrastructurally, there were not so many Weibel-Palade bodies in the endothelia without complete basement membrane. The morphological and functional changes of blood vessels were correlated with cancer differentiation and metastasis. These changes may provide biological feature of cancer and may be induced by cancer cells, vascular endothelia and mesenchymal cells. PMID- 1287460 TI - [Experimental study on platelet activating factor and systemic circulatory failure caused by ischemic liver]. AB - Ischemic hepatic failure is often accompanied by systemic circulatory failure. In hepatic graft failure, this circulatory derangement is reported to be cured by retransplantation. This suggests that ischemic liver might release some substance which causes circulatory depression. In the present study, the role of platelet activating factor (PAF) in systemic circulatory failure after liver ischemia was investigated. Partial hepatic ischemia was induced in ten dogs by clamping the afferent vessels to almost 70% of the liver for 60 minutes, and non-ischemic lobes were resected after declamping. Five were pretreated with 3 mg/kg of PAF antagonist (CV6209) i.v. (PAF antagonist group), and the others were pretreated with saline (control group). The mean arterial pressure markedly decreased after declamping in control group (89 +/- 25mmHg 25 min after declamping), but it did not fall in PAF antagonist group (155 +/- 221mmHg). Three died from either shock or hepatic failure within a week in control group, but none died in PAF antagonist group. In conclusion, ischemic liver was suggested to release PAF and depress systemic circulation. And a PAF antagonist was expected to be an effective drug for the circulatory derangement caused by ischemic liver. PMID- 1287461 TI - [Experimental study on the effect of ursodeoxycholic acid in liver transplantation]. AB - We investigated the effects of combination of cyclosporine A (CsA) and ursodeoxycholic acid (UDCA) in order to reduce hepatopathy caused by host-versus graft-reaction (HVG reaction). DA/S1c rats were used as donors, and LEW/Sea rats were used as recipients in orthotopic liver transplantation. The liver transplanted rats were divided to four groups as follows; group A was control that was not given CsA nor UDCA, group B was given CsA alone, group C was given UDCA alone and group D was given combination of CsA and UDCA. These groups were compared and evaluated in case of same dose of CsA that was administered with or without UDCA. The survival periods of group D were significantly longer than those of group B. Blood biochemical levels in group D were significantly lower than those of group B. Histological study of the liver graft of group D showed that destruction of hepatic structure was mild in comparison to that of group B. It was demonstrated that the combination of low dose of CsA and UDCA could prevent hepatopathy due to HVG reaction. These results suggested that addition of UDCA to CsA would be able to reduce the dose of CsA in clinical liver transplantation. PMID- 1287462 TI - [Cystic disease of right popliteal artery with spontaneous resolution]. AB - The case was 50-year-old man. He was admitted to our hospital suffering from intermittent claudication. DSA and CT showed stenosis of the right popliteal artery due to compression by the tumor like lesion. The adventitial cystic disease was suggested. Three weeks later he had no symptom. DSA and CT revealed no reappearance of the adventitial cystic disease. The popliteal adventitial cyst spontaneously decreased in size. It is a very rare case. PMID- 1287463 TI - [Radiolocalization of human esophageal cancer in athymic mice by a monoclonal antibody KIS-1: preliminary report]. PMID- 1287464 TI - [Antitumor effect of locally injected TNF.fibrin gel against murine colon 26 subcutaneous tumor: preliminary report]. PMID- 1287465 TI - [Induction of LAK-like cells in the regional lymph nodes and spleen by intralymph nodal injection of OK-432: preliminary report]. PMID- 1287466 TI - [The effect of CPT-11 in combination with interferon-alpha against human colon carcinoma heterotransplanted in nude mice: preliminary report]. PMID- 1287467 TI - [Evaluation of ketone body infusion for regenerating liver in the aged rat: preliminary report]. PMID- 1287468 TI - [Activation of pulmonary macrophage in early stage of experimental acute pancreatitis in rat: preliminary report]. PMID- 1287469 TI - [Study of NDP kinase/NM23 gene product in pulmonary adenocarcinoma: comparison of its expression in primary tissues with that in metastatic tissues: preliminary report]. PMID- 1287470 TI - [Experimental study on collateral vessels formation in jejunal auto transplantation: preliminary report]. PMID- 1287471 TI - [Efficacy of Futhan rinse solution following rat heart preservation: preliminary report]. PMID- 1287472 TI - [Radiolocalization of murine monoclonal antibody KIS-1F (ab')2 fragment in nude mice bearing human esophageal cancer xenografts: preliminary report]. PMID- 1287473 TI - [Correlation of DBA lectin binding and malignancy in breast cancers: preliminary report]. PMID- 1287475 TI - Nucleotide sequence of bup, an upstream gene in the bmi-1 proviral insertion locus. AB - The ability of Moloney murine leukemia virus to accelerate lymphomagenesis in E mu-myc transgenic mice is frequently associated with proviral integration within a locus denoted bmi-1. This locus contains not only the bmi-1 gene implicated as a collaborator with myc in lymphomagenesis but also just upstream an unknown gene denoted bup. The nucleotide sequence reported here for bup cDNA and flanking genomic sequences reveals that this widely expressed gene comprises at least 7 exons and potentially encodes a polypeptide of 195 amino acid residues. Computer searches with this polypeptide sequence revealed no close homolog in the databases, nor any conserved motifs, and it is unrelated to the product of the mel-13 gene, which lies just upstream from the bmi-1 homolog mel-18. PMID- 1287476 TI - Characterization of the genes encoding U4 small nuclear RNAs in Arabidopsis thaliana. AB - Three genes encoding U4 small nuclear RNA (U4 snRNA) in the higher plant Arabidopsis thaliana have been isolated and characterized. Two of the genes, AtU4.1 and AtU4.2, contain all the transcriptional signals known to be essential for U-snRNA gene activity in dicot plants: the Upstream Sequence Element (USE), the -30 TATA box and the downstream 3' end formation sequence. The USE and TATA elements are centered approximately four helical DNA turns apart, a feature characteristic of RNA polymerase II-transcribed U-snRNA genes of plants. The genes AtU4.1 and AtU4.2 are actively transcribed in transfected plant protoplasts and in Arabidopsis plants. Expression of the third gene, AtU4.3, could not be demonstrated. Since this gene is missing the downstream signal important for RNA 3' end formation, it probably represents a pseudogene. The genes AtU4.1 and AtU4.2 encode 152-153 nt long RNAs which show 85-89% sequence similarity with broad bean and pea U4 RNAs and 60-65% similarity with mammalian U4 RNAs. Arabidopsis U4 and U6 snRNAs can be folded into the base-paired Y-shaped model supporting the importance of the U4/U6 interaction during pre-mRNA splicing in plants as well as animals. PMID- 1287477 TI - Estrogen-induced synthesis of uterine proteins declines during aging. AB - The synthesis of total cellular as well as acid-soluble nuclear proteins and estrogen receptor is high in the uteri of young (22 weeks) and decreases to half in old (104 weeks) rats. Administration of estrogen induces the synthesis of these proteins significantly in young but shows no remarkable effect in old rats. Interestingly, a specific cytosolic protein of 45 kDa is stimulated about two fold after estrogen injection in young but not in old rats. These findings further establish the reduced responsiveness of uterus to estrogen in old age. PMID- 1287474 TI - Molecular aspects of pathological processes in the artery wall. PMID- 1287479 TI - Detection of antibodies to DNA: a technical assessment. AB - Antibodies to DNA can be found in the circulation of the majority of patients with Systemic Lupus Erythematosus (SLE). They are quite specific for this disease, which makes their detection an important diagnostic aid to the clinician. Fluctuations in the level of anti-dsDNA in an individual patient generally parallel the clinical state of that patient. Furthermore, the presence of anti-dsDNA may precede the diagnosis of SLE by more than a year. Four methods relevant for the measurement of anti-dsDNA antibodies are discussed in this paper: the ELISA, the indirect immunofluorescence test on Crithidia luciliae, the PEG assay, and the Farr assay. Each of these methods detects a part of the spectrum of anti-dsDNA antibodies present in the circulation of an individual patient. The ELISA is the most sensitive method, whereas the Farr assay is the most specific for SLE. However, with the latter method only antibodies of a relative high avidity for DNA are detected. Mild forms of SLE, where patients only have anti-dsDNA of a low avidity in their circulation, may easily be missed by this technique. Clinically, high avidity anti-dsDNA is related with the more frequent occurrence of nephritis, whereas low avidity anti-dsDNA antibodies are more often found in patients with central nervous system involvement. PMID- 1287481 TI - Quantitative assessment of the efficacy of oral ketoconazole for oral candidosis in HIV-infected patients. AB - Fifteen male patients with manifest oral candidosis due to Candida albicans, suffering from AIDS-related complex (ARC) or full-blown AIDS, were investigated both clinically and microbiologically before and about 1 and 4 weeks after 7 to 10 days of treatment with 200 mg ketoconazole p.o. per day. Candida albicans was quantitated in mouthwash fluid. The antimicrobial susceptibility of the Candida albicans isolates was assessed using the IC30 test. In the short term, clinical cure was obtained in 87%, mycological cure in 53%. In the long term, the corresponding figures were 56 and 9%, respectively. Eradication of Candida albicans was not possible if IC30 values exceeded 256 micrograms ml-1. While pretreatment counts of Candida albicans in those patients also taking zidovudine did not differ from those in the rest of the study population, both the clinical and the mycological efficacy of ketoconazole seem to be higher both in the short and the long term when administered together with zidovudine. In consideration of the high relapse rate after about 4 weeks, an interval treatment protocol with oral ketoconazole is proposed. PMID- 1287480 TI - Susceptibility of yeast isolates from defined German patient groups to 5 fluorocytosine. AB - Susceptibility and development of resistance to 5-fluorocytosine (5-FC) in Candida strains isolated from defined German groups of probands was investigated. 5-FC susceptibility was determined in a microdilution assay in yeast nitrogen base after 24 h of incubation at 37 degrees C. The range of 5-FC concentration investigated was between 0.015 and 16 micrograms ml-1. Isolates with a minimum inhibitory concentration (MIC) of > 16 micrograms ml-1 were regarded as 5-FC resistant. In total 335 Candida isolates were investigated, and 20 of them (6.0%) were found to be resistant. The Candida isolates were rather different with respect to their origin: out of 57 vaginal isolates from non-risk patients from Southern Germany 3.5% were 5-FC-resistant strains. One hundred and fifty-nine isolates from the urine of long-term intensive care patients from the whole of Germany showed 5-FC resistance (6.3%). Out of 74 isolates of different localization from intensive care patients of the University Clinics of Freiburg, 10.8% showed 5-FC resistance. Among 45 isolates from the oral cavity of HIV positive patients from the Frankfurt region, no 5-FC-resistant strain was found. The epidemiology of 5-FC resistance is based mainly on the percentage of non albicans isolates of the proband groups (C. tropicalis, C. krusei and others), and is less based on the frequency of Candida albicans serotype B isolates. In sequential observations with individual intensive care patients, no increase of 5 FC resistance in their Candida isolates could be observed with longer periods of hospitalization. PMID- 1287482 TI - Vaginal yeast colonization and promiscuity. A study of 197 prostitutes. AB - In order to study the role of promiscuity in yeast colonization of the vagina we examined vaginal smears of 197 prostitutes. Forty-two (21%) showed yeast infection on culture, and Candida albicans was isolated in 93% of these cases. This rate is comparable to the rates in reports of large series of non promiscuous women in the literature and does not suggest that promiscuity alone is a predisposing factor for vaginal yeast carriage. The rate of Candida infections was approximately the same in prostitutes taking oral contraceptives as in those not taking the pill (22 and 21%, respectively; P > 0.05). The prevalence of vaginal yeast colonization, however, was significantly higher in prostitutes under the age of 31 (30%) as compared with those over 30 (10%; P < 0.002), thus suggesting that women in the third decade of life are more prone to vaginal Candida infections than older age groups. PMID- 1287478 TI - The role of adhesion molecules in endothelial cell accessory function. PMID- 1287483 TI - Urticaria in the presence of intestinal yeasts--exacerbation by change of persorption? PMID- 1287484 TI - Long-time survival and morphological stability of preserved Sporothrix schenckii strains. AB - The survival and stability of morphological traits of 33 Sporothrix schenckii strains were evaluated. Strain subcultures were maintained under mineral oil for different periods of time lasting as long as 41 years, or in sterile distilled water for as long as 23 years. Of the 33 strains preserved under mineral oil, 28 (85%) maintained viability and unchanged macro- and microscopic characteristics. All of the 4 strains maintained in distilled water also remained viable, with no morphological changes. The results confirm the efficiency of the methods used to preserve strains of the pathogenous and anamorphous fungus Sp. schenckii, especially in laboratories of limited resources. PMID- 1287485 TI - Candidosis, aspergillosis and zygomycosis in an oncology department. AB - The incidence, aetiology and treatment of fungal infections in a 60-bed department of clinical oncology over 2 years is reported. During the second year, after the moving of the department from an old to a new building with an improved epidemiologic regimen, the incidence decreased rapidly, although the mortality due to systemic disseminated mycosis did not change. PMID- 1287487 TI - Dermatophyte infection in ichthyosis vulgaris. AB - A 31-year-old male who had been suffering from ichthyosis vulgaris developed hyperkeratosic lesions on the palms and soles and ungual alterations of both hands and feet. These lesions were resistant to topical corticosteroid and emollient cream treatments and were found to be caused by Trichophyton rubrum. Association of ichthyosis vulgaris and dermatophytosis--both very common disorders--is to our knowledge a very rare event. PMID- 1287486 TI - Onychomycoses due to Microascus cirrosus (syn. M. desmosporus). AB - Microascus cirrosus is very rarely the aetiological agent of onychomycosis. We report two additional cases of toenail infections caused by this fungus. PMID- 1287488 TI - Plans to safeguard your investments. PMID- 1287489 TI - Toothpaste, dental floss and tooth whiteners. A market review. PMID- 1287490 TI - Marketing the new dentistry. Tips on financial survival and the science of smiles. PMID- 1287491 TI - Dental dilemmas and professional autonomy. PMID- 1287492 TI - Against the odds. Remembering Dr. John N. Brimacombe. PMID- 1287493 TI - The implosion of dentistry. Why manpower is the profession's most pressing issue. PMID- 1287494 TI - The practice as a retirement asset. PMID- 1287495 TI - How's your patient recall? PMID- 1287496 TI - Ethics and dental research: principles and issues. PMID- 1287497 TI - Diagnosis from precise treatment goals. PMID- 1287498 TI - A history of orthodontics in Ontario. PMID- 1287499 TI - A lifetime of dedication. Remembering Dr. Frederick Joseph Conboy. PMID- 1287500 TI - Facts and fallacies in dental advertising. PMID- 1287502 TI - Communal water fluoridation in Ontario. 1992 status report. PMID- 1287503 TI - The politics of fluoride. PMID- 1287501 TI - Ethics and dental research: mechanisms for oversight and fostering a climate for ethical research. PMID- 1287504 TI - Pediatric patients in dental practice: behaviour management for the 1990s. PMID- 1287505 TI - Restoring primary teeth: introducing a new material. PMID- 1287506 TI - The lessons of practice: a pediatric case report. PMID- 1287507 TI - When leadership becomes a tradition. A history of pediatric dentistry in Ontario. PMID- 1287508 TI - The Educator. Remembering Dr. Albert E. Webster. PMID- 1287509 TI - Navigating the maturity curve. How to compensate long-time employees. PMID- 1287510 TI - Biochemical and morphological changes in rat lenses after long-term UV B irradiation. AB - The aim of the present study was to investigate biochemical and morphological changes in rat lenses following long-term UV B irradiation. After an irradiation period of 156 days with follow-up documentation by means of Scheimpflug photography, section-related biochemical analyses of the lenses as well as histological investigations were performed. The video-based Scheimpflug photography (Zeiss SLC) again proved to be an excellent method for the documentation of the UV cataract induced in rats. The biochemical analyses provided indications to potential damaging mechanisms; the section-related technique used allows more precise analyses than the processing of whole lenses in a cataract type restricted to a certain layer, as is the case with UV B damage. The most prominent biochemical findings were a significant decrease in glyceraldehyde-3-phosphate dehydrogenase in the equatorial region in the group with the highest irradiation dosage and a decrease in lactate dehydrogenase in the nuclear region. The histological results reflect the local extent of the UV damage as well as its progression after a prolonged irradiation period. PMID- 1287511 TI - Diagnostic tests for dry eye disease in normals and dry eye patients with and without Sjogren's syndrome. AB - In order to compare the diagnostic tests for dry eye disease and the results of conjunctival impression cytology, we examined three groups of eyes: 146 eyes of normal controls, 108 eyes of keratoconjunctivitis sicca (KCS) patients without Sjogren's syndrome (SS) and 102 eyes of patients with SS. The clinical tests (break-up time, Schirmer test, Rose Bengal staining) and conjunctival impression cytology specimens from the superior part of the bulbar conjunctiva were evaluated from all the eyes. Our results showed that the patients with KCS without SS have abnormal lacrimal tests (p < 0.001) without changes in impression cytology [nucleo/cytoplasmic ratio (N/C), p > 0.1]. The patients with KCS and SS have also abnormal lacrimal tests (p < 0.01), and their epithelial cells presented squamous metaplasia (N/C, p < 0.001). The goblet cell number remained unchanged in the three groups (p > 0.1). PMID- 1287512 TI - Susceptibility of +/+, +/nu and nu/nu BALB/c mice to ocular herpes simplex virus infection. AB - Athymic (nude) mice have played an important role in defining the function of the immune system and its role in infectious diseases. In the majority of these studies, heterozygous +/nu mice have been used as normal controls for the nu/nu mice, and it has been assumed that +/nu mice have essentially normal immune systems. We have compared the response of +/+, +/nu and nu/nu BALB/c mice following ocular infection with HSV-1 and have found that +/nu mice develop significantly more severe blepharitis, vascularization of the cornea, stromal keratitis and extraocular disease (herpetiform spread) than +/+ BALB/c mice. The extraocular disease was particularly severe in the +/nu mice, suggesting that factors regulating herpetiform spread of the virus are deficient in these mice. Susceptibility to lethal encephalitis did not differ between +/+ and +/nu mice. These results suggest that significant differences exist in the response to ocular HSV infection between +/+ and +/nu mice. PMID- 1287513 TI - Ocular pulsation correlates with ocular tension: the choroid as piston for an aqueous pump? AB - In 26 random out-patients, including 13 treated glaucoma patients and ocular hypertensives, the higher the ocular tension, the greater the pulse amplitude, by Alcon pneumotonometry, at a statistically significant level. In a single untreated hypertensive, when 2-hourly pneumotonometry was done for 24 h, the correlation was similar and significant. The higher the diastolic blood pressure, the higher the ocular pulsation, also significantly. Pulsation is suggested to be a pump, the choroid being the piston, contributing (1) to an increase in the outflow of aqueous humour and (2) to a homeostatic mechanism contributing to normalization of the intra-ocular pressure, wherein pulsation increases or decreases, as the intraocular pressure increases or decreases, respectively. PMID- 1287514 TI - Localization of elastic fibers and elastin mRNA in the uvea of chick embryo. AB - The distribution of elastic fibers and elastin mRNA was studied in the uvea of 19 day-old chick embryos by light and electron microscopy and in situ hybridization techniques using a 35S-labeled RNA probe. Light and electron microscopic examination revealed that elastic fibers were present in the uveal portion of the ciliary body, but not in the posterior choroid. Electron microscopically, elastic fibers were also found in Bruch's membrane. Abundant amounts of elastin mRNA were strictly localized in the fibroblasts in the uveal portion of the ciliary body, and no elastin mRNA was found in any of the cells in the posterior choroid by in situ hybridization. Cultured uveal tissue obtained from the ciliary body was found to produce large amounts of tropoelastin as compared with cultured posterior choroid. Using V8 protease peptide mapping and Northern blot analysis, the tropoelastin and its mRNA produced by the ciliary body were identical to those produced by the smooth muscle cells in the aorta. The results suggest that elastin is synthesized in the ciliary body, acting as a supporting substance in this area. PMID- 1287515 TI - Corneal concentration and systemic absorption of cyclosporin-A following its topical application in the rabbit eye. AB - To ascertain the corneal storage and the possible systemic absorption of 2% cyclosporin-A (CsA) eyedrops, the authors studied, by RIA with monoclonal specific antibodies, the corneal and blood levels of the drug following its topical administration on healthy albino rabbit eyes. When topical CsA was administered following a low-dose application schedule [such as a single dose of 100 microliters every 12 h for 5 days (group 1)], CsA corneal levels of 260.8 +/- 59.8 ng/ml and blood levels of 55.67 +/- 24.4 ng/ml (expressed as means +/- SD) were achieved. These levels significantly increased to 1,111.27 +/- 449.4 ng/ml (p > 0.0001) and 88.66 +/- 59.7 ng/ml (p > 0.05), respectively, when a higher dosage was used [100 microliters every 6 h for 10 days (group 2)]. It is shown that a dose-dependent corneal concentration of CsA, due to a cumulative effect, is achieved in the intact rabbit cornea following topical application of the drug. Systemic absorption of CsA, although irregular, does exist. Therefore, when using topical 2% CsA as in this study, a systemic effect of the drug (especially in low weight animals) should be considered when analyzing the results of topical application. PMID- 1287517 TI - Connective tissue of the orbital cavity in retinal detachment: an ultrastructural study. AB - The connective tissue from Tenon's capsule of 7 patients who underwent surgery for retinal detachment was studied ultrastructurally. Five patients were 58-70 years old, and 2 were young adults. The Tenon capsules of 6 children and of 2 aged patients without retinal problems were used as controls. In young controls the Tenon capsule was composed mainly of round, smooth collagen fibrils and a few elastic fibers. The collagen fibrils varied in size from 70 to 110 nm. In the aged patients with retinal detachment, the collagen fibrils showed marked variation of size and also abnormalities of shape in 4 out of 5 cases. The diameter of collagen fibrils varied from 32 to 160 nm, and the elastic fibers were fewer as compared with controls. The possibility arises that age-related structural changes of the orbital connective tissue could predispose to retinal detachment. PMID- 1287516 TI - Comparison of effects of oxygen and antioxidative enzymes on cell growth between retinal pigment epithelial cells and vascular endothelial cells in vitro. AB - We assayed the proliferation of porcine retinal pigment epithelial (RPE) cells, bovine melanotic and amelanotic RPE cells, and bovine aortic endothelial cells exposed to 20, 10 and 5% oxygen and compared their responses to oxygen and antioxidative enzymes (superoxide dismutase and catalase). Irrespective of the cell type, the cell growth was optimal in 10% oxygen that is most closely approximating to the oxygen concentration prevailing in the cellular environment of the choroid and the retina in vivo. However, the effects of oxygen concentrations were cell specific because bovine endothelial cells were influenced by lowering of oxygen concentrations more significantly than bovine and porcine RPE cells. Moreover, addition of antioxidative enzymes caused significant improvement in growth of porcine RPE cells, but had no significant effects on bovine RPE cells. On the contrary, the bovine vascular endothelial cells represented the only one cell type significantly inhibited by antioxidative enzymes, i.e., a decrease in reactive intermediates of oxygen was seen in the media. Our results show that responses of vascular endothelial cells to reactive species of oxygen were distinctly different from those of RPE cells and more easily influenced by the environment related to hypoxia than RPE cells. PMID- 1287518 TI - Rabbit diurnal ocular tension variations. AB - Ocular tension recorded by pneumatonography was estimated at 4-hour intervals during six consecutive 24-hour periods in 8 New Zealand rabbits. The animals had been acclimatized for more than 8 weeks to artificial light from 08.00 to 20.00 h and dark for the other 12 h. Inter- and intrarabbit consistency was enough to allow the generalization that the lowest pressure occurred at noon (mean -0.8 mm Hg from baseline average), while the highest pressures (mean + 1.2 mm Hg above baseline average) occurred at 16.00 and 20.00 h. Only three other studies have measured rabbit ocular tensions throughout 24 h, but for shorter periods: one observed a light-induced rise as in the present study, but the other two studies found a rise during darkness. PMID- 1287519 TI - Reasonable expectations: from the Institute of Medicine. Interview by Paul M. Schyve. AB - When the Omnibus Budget Reconciliation Act of 1989 created a new agency in the U.S. Public Health Service to foster the development of practice guidelines and outcomes and effectiveness research, the Institute of Medicine was engaged to develop the criteria for guideline development and medical review. The new agency -the Agency for Health Care Policy and Research (AHCPR)--has used those criteria to develop and disseminate its first three commissioned guidelines, released this spring. Those criteria are elaborated in the IOM's 1990 book. In a second book, released this summer, the IOM Committee on Clinical Practice Guidelines reviews the constructive expectations for guidelines and the conditions needed to ensure rigor in their development, application, evaluation, and revision to help realize these expectations. Key recommendations for action are development of an instrument to assess guidelines and establishment of an organization to carry out the assessment of guidelines. In an appendix, the report offers "A Provisional Instrument for Assessing Clinical Practice Guidelines." While asking that organizations undertake more field testing and revision of the instrument, the Committee on Clinical Practice Guidelines believes that the provisional instrument will be useful as an educational tool for those beginning to develop guidelines, a self-assessment tool that developers of guidelines can use to check their work, and a tool for external groups to use in judging whether a set of guidelines should or should not be recommended or adopted. PMID- 1287520 TI - Awareness, assimilation, and adoption: the challenge of effective dissemination and the first AHCPR-sponsored guidelines. PMID- 1287521 TI - Practice parameters: development, evaluation, dissemination, and implementation. PMID- 1287522 TI - AHCPR-NLM joint initiative for health services research information: 1992 update on OHSRI. PMID- 1287523 TI - Implementing clinical practice guidelines: social influence strategies and practitioner behavior change. AB - Clinical practice guidelines offer potentially valuable tools for rationalizing health care delivery and improving patient outcomes. Currently, major efforts are under way to develop, test, and refine guidelines for a wide variety of medical conditions and procedures. Although methods for producing guidelines are fairly well understood and continue to improve, experience suggests that guidelines rarely translate directly into changes in practice. For various reasons, including physician resistance or incomplete understanding of the need for guidelines, they have proven difficult to implement. This article describes a broad range of strategies for implementing clinical practice guidelines based on the social influences that affect health practitioner behavior. The article also examines issues surrounding the selection and use of individual strategies or combinations of strategies in specific efforts to improve the quality of health care. PMID- 1287524 TI - Implementing clinical guidelines: a quality management approach to reminder systems. AB - "Reminders" (timely notices about specific clinical events to physicians or patients) are useful strategies for implementing clinical guidelines. These systems can vary widely in content, design, and purpose. This variability makes it difficult to compare systems or predict a reminder's efficacy in a particular setting. In this article, the authors suggest that too much attention has been paid to proving the efficacy of reminder systems as a general strategy or a comprehensive solution. Rather, the usefulness and effectiveness of reminder systems will be better appreciated when quality management principles are applied to designing, implementing, and maintaining them. Physicians must participate in finding the best solutions for clinical process problems, and reminder systems- when implemented as the "best solution"--must be monitored and improved continually on an ongoing basis to continue to meet physicians' needs. PMID- 1287525 TI - The use of continuous quality improvement methods in the development and dissemination of medical practice guidelines. AB - The federal government is currently supporting the development and dissemination of clinical practice guidelines. Physicians fear that payers who promote guidelines are more interested in reducing variation to control their behavior and contain health care spending than in improving quality of care. There is also apprehension that guidelines will shift the responsibility for quality to parties external to the physician-patient relationship and the local professional community. Continuous quality improvement (CQI) methods provide an avenue for physician responsibility and participation in guideline development which can alleviate these concerns. This article describes the efforts of one health maintenance organization (HMO) to use CQI techniques to mobilize plan physicians to develop, disseminate, and implement practice guidelines in a manner that satisfies the needs of physicians, patients, and the HMO. PMID- 1287526 TI - Using the analytic hierarchy process (AHP) to develop and disseminate guidelines. AB - To be effective, practice guidelines must accommodate the unique circumstances of individual patients. This article describes how the analytic hierarchy process (AHP), a decision-making technique, could be used to create flexible guidelines by linking guideline developers and clinical decision makers as coworkers in a common decision-making process. The advantages of using this approach for guideline dissemination are discussed and compared with other methods for disseminating and implementing guidelines. The clinical feasibility of the AHP approach is also reviewed. PMID- 1287527 TI - Practice guidelines: will they have an impact in high-tech cardiology? PMID- 1287528 TI - The case for intensive dissemination: adoption of practice guidelines in the coronary care unit. AB - Medical practice guidelines are being embraced enthusiastically by subspecialty and government organizations, but although hundreds have been developed at great public and private expense, there are few examples of how they have improved the quality of care or reduced health care costs. This article reports documented experience in changing physician behavior after implementing medical practice guidelines in the coronary care unit without altering physician incentives or imposing the threat of sanctions. Guideline adoption did require significant attention to the implementation process, including endorsement of guidelines by local "opinion leaders," validation by local data, and an intensive and concurrent implementation strategy. PMID- 1287529 TI - Implementing practice guidelines through a utilization management strategy: the potential and the challenges. AB - Although there is currently much enthusiasm for practice guidelines, far more energy and resources have been expended on their development than on their implementation. A prospective interventional trial was performed using a previously validated explicit practice guideline (decision aid) to decrease the hospital length of stay for selected "low-risk" patients with chest pain. Utilization management (UM) coordinators (RNs) and physicians were chosen to implement the guideline since these resource people are available in most hospitals, allowing for generalization of the experience. With explicit review criteria used for 624 patients, it was found that when the guideline was applied by UM coordinators, it had a sensitivity of 0.85, a specificity of 0.90, a positive predictive value of 0.76, and a negative predictive value of 0.94. The attending physicians failed to override falsely classified low-risk patient recommendations 51% of the time. Implicit review judged that outcome might have theoretically been worsened in two of these patients. Follow-up at 30 days after admission, however, revealed no untoward sequelae in falsely categorized patients discharged according to the guideline. Utilization management appears to be a promising mechanism for guideline implementation that is available in most institutions. However, the accuracy with which UM coordinators implement guidelines should be assessed rigorously. Guidelines should be implemented in an environment of checks and balances in which physicians have the ultimate responsibility for their patients' care. PMID- 1287530 TI - Presentation of drug prescribing guidelines and physician response. AB - Most Medicaid Drug Use Review (DUR) Programs disseminate prescribing practice guidelines by providing written reviews to physicians about specific prescribing practices that do not follow established criteria and inviting their comment. This study reviewed physicians' written responses to explore relationships between DUR communications and the degree to which these communications affect awareness of prescribing issues, increase knowledge, change erroneous beliefs, and generate intentions to apply the information appropriately. The form, content, and effective tone for all responses received in 1990 regarding five different drug therapy issues (N = 240) was recorded. Response rates, comprehension, counterarguments, and prescribing intentions varied by drug therapy issue. Attention to the communication process could improve the dissemination of prescribing practice guidelines by DUR Programs. PMID- 1287531 TI - The impact of status asthmaticus practice guidelines on patient outcome and physician behavior. AB - This study assesses the effects of a status asthmaticus guideline on patient outcome and pediatrician behavior in a staff model health maintenance organization (HMO). The guidelines were drafted by an asthma specialist in the HMO and then discussed with key clinical personnel. A preprinted protocol order form was developed to help implement the guideline into clinical practice. The medical records of pediatric patients admitted to the hospital with status asthmaticus before (N = 67) and after (N = 59) guideline development and implementation were reviewed. This study demonstrates that locally developed, treatment-specific guidelines based on scientific evidence and combined with a staff consensus process and a user-friendly protocol form can influence physician behavior and patient outcome positively. PMID- 1287533 TI - How insurers, purchasers, and employers view their need for guidelines: report of Washington Business Group on Health--AHCPR focus groups. PMID- 1287532 TI - Guidelines for prophylactic platelet transfusions: need for a concurrent outcomes management system. PMID- 1287534 TI - Faulkner & Gray, Group Health Association of America put practice guidelines to the test in real-world settings. PMID- 1287535 TI - A cross-sectional study of the relationship between age and current health status for persons with spinal cord injuries. AB - As life expectancies of persons with spinal cord injuries increase, this population is aging rapidly. This trend requires that increasing attention be given to the healthcare needs of older persons with spinal cord injury. Follow up data on 11,117 persons injured since 1973 were analyzed by current age at 15-year intervals. Mean time postinjury was 4.7 years. Several trends were observed when comparing persons currently in the 16-30 year age group with persons in the oldest age group (age 76+). The percentage of persons independent in selfcare decreased from 61.9% to 29.1%. Ventilator use increased from 1.7% to 4.3%. Nursing home residence increased from 1.4% to 22.2%. The percentage of persons rehospitalized during the most recent year increased from 26.5% to 33.7%. Age was an important predictor of health status, but time postinjury was less important, perhaps due to the study's short postinjury time frame. While few differences in health status were observed in individuals between 16 and 60 years of age, persons in the oldest two age groups demonstrated lower levels of health status than younger individuals. PMID- 1287536 TI - Young spinal cord injured patients in nursing homes: rehospitalization issues and outcomes. AB - Most spinal cord injured (SCI) patients are discharged to their homes and families after they complete their initial rehabilitation program. Nursing homes, however, were the discharge destinations for 3.9% of all SCI patients nationally. When a nursing home is the only discharge option for a young SCI adult, certain economic, medical and psychosocial incongruencies make this placement potentially stressful for both the nursing home staff and the young patient. This study of the rehospitalization of 12 SCI patients under the age of 50 who were discharged to nursing homes explores the issues of cost, care and outcome during their first year following nursing home admission. Nine of the 12 patients were rehospitalized a total of 21 times, mainly for urinary tract infections and decubiti. Charges for 18 of these 21 rehospitalizations amounted to over $423,110 for 599 days of care. Four of these 9 patients died before the end of the first year. Although this is a retrospective study of the medical records and follow up data for a small key group of SCI patients, it calls attention to the need for continued investigation into the outcomes of a minimally visible population that lacks advocacy for change. PMID- 1287537 TI - New estimates of the direct costs of traumatic spinal cord injuries: results of a nationwide survey. AB - New estimates of the direct costs of traumatic spinal cord injuries (SCI) are obtained from a comprehensive survey of the US SCI population. These direct costs, defined as the value (in 1988 dollars) of resources used specifically to treat or to adapt to the SCI condition, represent the average experience of the US SCI population. Responses to a detailed questionnaire administered to a sample of traumatic SCI persons in the United States provide the primary source of data for this study. Analysis of this survey data indicates that more recently injured SCI persons (ie those injured since 1970) spent an average of 171 days in a hospital over the first 2 years post injury. Initial hospital expenses will average $95,203. Home modification costs in excess of $8,000 can also be expected. After recovery and rehabilitation, a SCI person will pay, on average, $2,958 per year in hospital expenses and $4,908 per year for other medical services, supplies and adaptive equipment. Personal assistance costs and costs of institutional care will average $6,269 per year. These cost estimates represent the incremental costs of SCI, ie they exclude any costs that would have been incurred in the absence of SCI. PMID- 1287538 TI - Correlation of bacteriological flora of the urethra, glans and perineum with organisms causing urinary tract infection in the spinal injured male patient. AB - Positive urine cultures are common and often asymptomatic in the male spinal injured patient performing self clean intermittent catheterisation. It is possible that the positive urine cultures result from contamination from the colonised urethra at the time of catheterisation. This contamination could result in true infection of the bladder urine or yield false positive results, explaining the frequently seen asymptomatic cases. In a prospective study positive urine cultures were found on 58 occasions (74%) in 10 asymptomatic patients studied. In 19% of screenings, with positive urine cultures, an identical organism was cultured from the catheter specimen of urine, the perineum and the urethra. The flora of the anterior urethra is strongly correlated to that of the perineum (37.1%), as well as that of the bladder (52.6%). In 4 patients a correlation also existed between the urethra and fingers, and the perineum and fingers. This was associated with an increased incidence of positive urine culture in these patients. Suprapubic aspirates of urine before and after catheterisation cultured the same organisms. However, quantitative culture revealed colony counts that approached a 10-fold increase following catheterisation in one patient. This suggests that catheterisation is at least partially responsible for ascending infection in this group of patients. Catheter specimens were found to be a good representation of the bladder urine, with an 87.5% correlation. PMID- 1287539 TI - N-nitrosamine generation by urinary tract infections in spine injured patients. AB - Urine was collected from 33 patients resident at the Welsh Spinal Injuries Unit and analysed for volatile N-nitrosamines by gas chromatography. N-nitrosodime thylamine, N-nitrosopiperidine or N-nitrosopyrrolidine was detected in 32 of the samples. Thirty-one of the samples were infected by one or more microbial species. Nitrate and N-nitrosamines were not found in the sterile urines of a group of 10 control individuals exposed to the same dietary and environmental influences as the spinal patients. Although N-nitrosamines were found in some of the catheter drainage system products, they did not elute into urine on 24-h exposure. In addition, 6 of the nitrosamine-containing urines had no contact with drainage systems as they were collected from spinal patients who were capable of independent voiding. It was concluded that the nitrosamines detected in the urines arose from the bacterial nitrosation of urinary amines. These results support the hypothesis that chronic urinary tract infection may have a role in the aetiology of bladder cancer in spine injured patients. PMID- 1287540 TI - Event-related brain potentials during orienting to auditory and visual stimulation in spinal cord injured humans. AB - In intact humans, deprivation of somatosensory and kinesthetic sensations result in significant alterations in perception and information processing. There have been very few studies to discover if the loss of sensation with spinal cord injury (SCI) in humans affects perceptual operations. We hypothesized that the SCI participant would either exhibit arousal, perceptual, and information processing alterations similar to experimentally sensory deprived subjects (who provide the closest human analogue), or that the somatosensory cortex would show reorganization for the processing of other modalities of stimulation. The subjects consisted of 16 paraplegic, 13 quadriplegic, and 22 non SCI controls. Subjects received an auditory orienting task consisting of a 500 Hz tone presented 20 times each at 66, 75, 88, and 101 db and a visual orienting task incorporating light flashes of 115, 123, 131, and 140 lux presented 20 times each. EEG information processing data were recorded from C3 and C4 for 100 msec prior to and 500 msec post stimulation. Information processing variables, analyzed as event-related potentials, indicated that the somatosensory cortex of SCI groups had a flattened response to auditory stimulation. The control group had a significantly larger P2 component. We concluded that these data signified that the somatosensory cortex did not reorganize function in response to chronic deafferentation nor was the SCI subject hyperresponsive to stimulation. PMID- 1287541 TI - Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics. AB - To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg). The reduction in SBP during control HUT (-12.0 +/- 4.6 mmHg) was four-fold larger (p = 0.017) than during HUT following exercise (-3.1 +/- 3.9 mmHg). DBP during HUT was not altered in either condition. A single bout of intense, dynamic arm crank exercise eliminated orthostatic hypotension in paraplegics. Equal HR response with smaller reduction in SBP during HUT after exercise was consistent with a measured increased sensitivity of the carotid-cardiac baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287542 TI - An examination of dietary intakes and nutritional status of chronic healthy spinal cord injured individuals. AB - To examine the nutritional composition of the dietary intake of chronic healthy spinal cord injured (SCI) individuals, 33 subjects affiliated with 3 SCI rehabilitation centers logged their food consumption for 7 days. Prior to record keeping, subjects were trained by a registered dietitian on the accurate recording of their standard food choices and portion size, and were provided with scales to weigh food accurately. Dietary macro and micronutrients were analyzed with a computer software package, with nutritional analysis compared to the recommended daily allowances (RDA) of the Food and Nutrition Board of the National Academy of Sciences. Analysis showed caloric intake to be 75% of that recommended for able bodies persons, with a high reliance on fat for calories. Fat intake accounted for 37.9% of calories, well above the recommended level of 30%, but typical of the American diet. The ratio of polyunsaturated to saturated fat was approximately one half the recommended level, with carbohydrate calories averaging 16.5% below optimal RDA. Protein consumption was within normal range, but average dietary fiber was only 25% of recommended levels. Micronutrient analysis showed deficiencies in both water and fat-soluble vitamins, with suboptimal intake of multiple minerals. Given the apparent reliance on a high-fat and low-carbohydrate diet, this research shows that nutritional intervention and education of SCI persons are needed, and that a registered dietitian should be included in the SCI health care team. PMID- 1287544 TI - Oesophageal trauma in patients with spinal cord injury. AB - Oesophageal perforations associated with cervical fractures occur from a variety of injuries. Fractures of the cervical spine, blunt trauma and penetrating injuries such as gunshot wounds, knives and missiles, perforate the cervical oesophagus. This retrospective study consists of 24 patients with an oesophageal perforation and cervical fracture. Motor vehicle accidents were responsible for 54% of the oesophageal perforations. The other oesophageal injuries were related to anterior spine surgery, gunshot wounds and sports-related activities. The clinical features related to these injuries included the obvious signs of an oesophageal perforation as well as fever of unknown origin, leukocytosis and unexplained persistent tachycardia. A variety of techniques was used to establish the diagnosis. All the patients had treatment for the cervical fracture and 20 patients required surgical repair of the oesophagus. The most common oesophageal complications were stricture of the oesophagus (54%) and oesophageal diverticulum (10%). The other complications were atelectasis, pneumonia, tracheobronchitis, pulmonary embolism, cervical osteomyelitis, cervical abscess, mediastinitis, septicemia and cervical fistulae. These patients have a serious life-threatening illness that may be difficult to diagnose and treat. PMID- 1287543 TI - Pregnancy, labor and delivery post spinal cord injury. AB - There are approximately 3,000 women of childbearing age who become spinal cord injured each year in the United States. There are few reports in the literature that address pregnancy, labor and delivery in this patient population. We are reporting on 22 women post spinal cord injury who had 33 pregnancies. There were equal numbers of paraplegic and quadriplegic women. Three pregnancies aborted, one spontaneously. The babies were near normal or normal weight with one exception. The mothers waited 5 years on average to become pregnant. Cesarean section was performed on 43% of pregnancies. Abnormal presentations occurred in over 10% of pregnancies. Indications for cesarean section included 5 that were repeats; the remainder were necessary due to bleeding (1), breech presentation (1), transverse presentation (2), lack of progress (2), onset of labor 1 day post spinal fusion, and a mother's request to have tubal ligation. Epidural anesthesia was selected for 9 deliveries; 6 of these patients had controlled autonomic hyperreflexia. Five general and 4 local anesthetics were used, and 12 patients received no anesthesia. Diagnostic ultrasound and amniocentesis were used selectively. Complications included autonomic hyperreflexia (9), frequent urinary tract infections, infected pressure sores (3, 2 resulting in below-knee amputations), seizures during and after delivery, pneumonia, bladder stones (2), episiotomy dehiscence (1), and breakdown of spinal fusion. The newborns were healthy, although one double footing breech vaginal delivery had an APGAR of 1 at 1 min, 7 at 5 min and 9 at 10 min. One premature baby, who weighed only 1600 g, was a precipitate birth at home unattended. Implications for the care of pregnant SCI women are discussed. PMID- 1287545 TI - Morphometric evaluation of myofibrillar mitochondria in experimental administration of ethylene glycol. AB - The authors carried out morphometric analysis of the surface, area, circumference and shape of myofibrillar mitochondria in rats submitted for acute experimental intoxication with ethylene glycol. The measurements were taken at 12 and 24 hours after intoxication and compared with those in the control group. A significant increase in mitochondrial circumference and surface area was seen as early as 12 hours with their shape being more rounded than elongated. At 24 hours of the experiment the parameters further increased. The use of computer image analysis permitted an objective and measurable confirmation of changes in electronograms and revealed the presence of disorders in the phase in which traditional methods were useless. PMID- 1287546 TI - Ultrastructural signs of myocardial damage due to acute experimental intoxication with ethylene glycol. AB - The authors carried out ultrastructural studies of the myocardial sections from inbred Wistar rats in the course of acute experimental poisoning with ethylene glycol. It was shown that slight mitochondrial swelling with clearing of the matrix, myofibrillar edema with decreased electron density of the sarcoplasma and widening of channels of the smooth intraplasmatic reticulum were visible as early as at 12 hours after intoxication with no changes in light microscopy. The changes were located mainly in the subendocardial layer of the ventricles and papillary muscles. At later stages of the experimental ultrastructural changes markedly progressed. Mitochondrial swelling enhanced with destruction of mitochondrial crests, myelin-like figures formed, myofibrillar necrosis and contraction bands developed and segmental or complete dissection of the intercalated disk edges appeared. The chages were scattered all over the myocardium predominating in the subendocardial layer and papillary muscles. PMID- 1287547 TI - Relation between cardiovascular pathologic conditions and malignant tumours as seen by pathologist. I. Frequency of malignant neoplasms in the population with myocardial hypertrophy as seen by pathologist. AB - Relatively low co-existence of malignant neoplasms and chronic cardiovascular disease was documented in this work the emphasis being put on the conditions running with myocardial hypertrophy. The percentage of malignancy in the total autopsy material of 5821 men and 6849 women was 27.8 and 23.0 resp., and in the subgroup with heart weight 300-400 g, 36.8 and 31.0 resp. This percentage was significantly lower in separated subgroups of: a. arterial hypertension, 6.6 and 10.2, b. cardio-pulmonary syndrome, 23.0 and 18.5, c. healed myocardial infarct accompanied by myocardial hypertrophy, 13.3 and 11.7, d. acquired valvar deformity, 15.3 and 10.1. The subgroup of heart weight 150-250 g showed 57.2% and 46.6% of cases with malignancy while that of cardiac weight over 600 g-7.4% and 5.7%. In the subgroup of normal right-(2-3 mm) and left-ventricular (10-12 mm) wall thickness corresponding percentage equalled 29.4 and 30.1, in the subgroup of right-ventricular wall thickness over 6 mm--14.4 and 8.8, and in that of left ventricular wall thickness over 18 mm--12.5 and 9.4. Scanty available information suggests some antimitotic activity of catecholamines believed to condition that of chalones. Catecholamines are also attributed with the stimulation of myocardial hypertrophy. The correlation of our findings with assumptions mentioned above seem to justify a hypothesis, or only a possibility, that compensatory mechanisms active in the cardiovascular diseases create an unfavourable background for the development of neoplasm. PMID- 1287548 TI - [Present-day pathological physiology]. PMID- 1287549 TI - Spindle cell hemangioendothelioma--case report. PMID- 1287550 TI - Fibrinoidal leucodystrophy (Alexander's disease) at 13 months girl. A case report. AB - The case of Alexander's fibrinoidal leucodystrophy that was presented below is an exemplar of extremely rare degenerative disease of the CNS. On the grounds of the clinical course of the disease it seems that our case can be reckoned as an early childhood form of Alexander's disease. An interesting difference that pays attention is the marked hydrocephalus. In the most cases of Alexander's disease the volume of ventricular system is normal however most of authors expresses that it sometimes can be slightly and insignificantly enlarged. PMID- 1287551 TI - Pathomorphology of the skin diseases especially of tumours. Part II. Neoplasms and pseudo-neoplastic proliferations. PMID- 1287552 TI - Setting priorities for pediatric research--a time for leadership. PMID- 1287553 TI - Molecular genetics of neuronal ceroid lipofuscinoses. AB - This overview describes recent advances in molecular biology of neuronal ceroid lipofuscinoses (CLN). Despite intensive research during last 20 years, the basic defects of these autosomal recessive-progressive encephalopathies of childhood remain unknown. Consequently, no specific cure is available. Methods of positional cloning (reverse genetics) starting from random linkage approach have been applied to search for gene defects in the infantile and juvenile forms of the disease. The results of this random search for disease loci have for the first time revealed molecular heterogeneity of CLN diseases. The gene defect causing the infantile form has been assigned to 1p32 in the Finnish family material, whereas the disease locus of the juvenile form has been localized to 16p12 in European and Canadian families. Finally, the gene defect causing the late infantile form has been excluded from both 1p32 and 16p12 chromosomal regions, referring to a third, still unknown locus causing CLN disease. Consequently, reliable prenatal and carrier diagnostics have now become possible in families with the infantile and juvenile forms of the disease, and DNA-based prenatal diagnostics have been successfully applied in the infantile form. Most importantly, the assignment of gene loci has brought these fatal brain diseases within the reach of molecular cloning strategies that eventually will result in revealing both the infantile and juvenile CLN genes and in identifying corresponding gene products. PMID- 1287554 TI - Differential developmental expression of the rat kininogen genes. AB - The rat liver expresses two low molecular weight kininogens (T-KG and K-KG). Although they share 90% of the nucleotide sequence in their 5' flanking regions, T- and K-KG genes are differentially regulated. The T-KG gene is inducible, and its protein is a potent thiol-protease inhibitor. In contrast, K-KG gene is expressed constitutively and encodes the precursor of the vasoactive nonapeptide bradykinin. To further elucidate the differential regulation of T- and K-KG genes, we examined their developmental expression in the Sprague-Dawley rat. Northern blots of total liver RNA were probed with oligonucleotides complementary to T and K-KG mRNA under high-stringency conditions. A single T-KG mRNA (1.8 kb) and two K-KG mRNA species (1.6 and 2.3 kb) were consistently detected at all ages studied. Steady state T-KG mRNA levels increased 3.5-fold at birth and remained high during the 1st week of postnatal life only to decline thereafter. T-KG immunoreactivity in the liver and plasma determined by Western blot analysis paralleled T-KG mRNA expression. In marked contrast, K-KG mRNA expression was not altered during the transition from fetal to neonatal life, nor was it affected by postnatal maturation. The results demonstrate that the fetal rat liver synthesizes kininogens and that T- and K-KG genes are differentially regulated during development. Up-regulation of T-KG synthesis after birth may serve a protective function in the newborn via its antiprotease activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287555 TI - Developmental cellular electrophysiologic effects of propafenone on the rabbit atrioventricular node. AB - Transmembrane recordings and surface electrograms were used to evaluate the influence of propafenone on the cellular electrophysiology of isolated neonatal and adult rabbit atrioventricular node (AVN) preparations. An automatic interval of 863 +/- 82 ms (mean +/- SEM, n = 14) in neonates was found to be significantly shorter than the 1510- +/- 205-ms (n = 12) automatic interval observed in adults. Propafenone in a concentration of 5 x 10(-6) M significantly increased the automatic interval of neonatal pacemakers but not that of the adult preparations. These changes in automaticity produced by propafenone were not dependent on the adrenergic receptor-blocking action of the drug. The pacemaker escape time after overdrive pacing was also shorter in the neonate than in the adult. Propafenone prolonged the escape time of the neonatal tissues but not those of the adult. AVN refractory period, A-H interval, and antegrade Wenckebach rate were comparably increased in a concentration-dependent manner in both age groups. The maximum diastolic potential was decreased by propafenone in the neonatal atrionodal tissue but not in other regions of the AVN and not in any region of the adult AVN. Action-potential duration was increased in all regions of the AVN in both age groups. Action-potential amplitude and maximum upstroke velocity were decreased by propafenone in both age groups. Unlike other excitable tissues of the heart, the action-potential duration of AVN nodal cells increased with decreasing pacing intervals as the pacing interval approached the Wenckebach interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287556 TI - In situ morphology of the foramen ovale in the fetal and neonatal rat. AB - In situ cross-sectional morphology of the foramen ovale was studied after rapid whole-body freezing of the fetal and neonatal rat. In the fetus, the foramen ovale was open widely toward the left atrium with a thin, short primum septum. The opening area of the foramen ovale was 40% of the cross-section of the thoracic inferior vena cava, and the ratio of the long diameter to the short diameter was 2 to 1. After birth, the primum septum became longer, thicker, and straighter, with less leftward bowing. The opening of the foramen ovale diminished in the first 2 d and closed completely 3 d after birth. Postnatal thickening of the primum septum was very remarkable, increasing by 400% in the first 2d, while only minimal change was noticed in the right and the left atrial walls. The length of the primum septum was short and was only 90% of the diameter of the fossa ovalis in the fetus. It increased and reached 97% and 111% of the diameter of the fossa ovalis 1 and 2 d after birth, respectively. The septum secundum also grew rapidly after birth, and its length and width increased by 40% and 29% after 1 and 2 d, respectively. These observations indicate a sudden, explosive growth of the atrial septum in the early neonatal period in the rat. PMID- 1287558 TI - Alae nasi activation in preterm infants during oral feeding. AB - Preterm infants may demonstrate impaired ventilation during oral feeding with resultant hypoxemia and hypercarbia. This study was designed to determine whether infants activate a representative upper airway muscle, the ala nasi, in response to these ventilatory changes. Ten preterm infants (postconceptional age at study 35 +/- 4 wk, weight 2.2 +/- 0.1 kg) were studied during a control period, continuous feeding, subsequent intermittent feeding, and a period of nonnutritive sucking. Nasal airflow was measured with a pneumotachometer to quantify minute ventilation. The alae nasi electromyogram (EMGAN) was recorded with surface electrodes, and sucking pressure was detected by a catheter in the feeding nipple. End-tidal CO2 and O2 saturation were also recorded during each period. The percentage of breaths associated with EMGAN activity increased from 41 +/- 13% during the control period to 95 +/- 5% and 93 +/- 7% during continuous and intermittent sucking, respectively (p < 0.05). Eighty-seven +/- 5% of EMGAN activity occurred during inspiration. During continuous and intermittent sucking, the amplitude of EMGAN activity also increased (6.8 +/- 5.2 and 6.7 +/- 4.0 arbitrary units/breath, respectively) compared with the control period (2.4 +/- 2.8 units/breath, p < 0.05). In association with the increase in EMGAN activity, O2 saturation fell from 98 +/- 1% in the control period to 95 +/- 1% during both continuous and intermittent feeding (p < 0.05), and minute ventilation fell from 274 +/- 80 mL/min/kg during the control period to 190 +/- 81 and 208 +/- 57 mL/min/kg during continuous and intermittent feeding, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287557 TI - Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone. AB - We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2 4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones. PMID- 1287559 TI - Docosahexaenoic acid status of term infants fed breast milk or infant formula containing soy oil or corn oil. AB - The objective of this study was to compare circulating lipid docosahexaenoic acid [22:6(n-3), DHA] levels in term infants fed a powdered (CORN oil) or liquid (SOY oil) infant formula or human milk (HM). Infants whose mothers chose not to breast feed were randomly assigned to the CORN or SOY formula group. The formula fat differed in linolenic acid [18:3(n-3)] content: it was 0.8% for the CORN and 4.8% for the SOY. Linoleic acid [18:2(n-6)] was 31.5 and 34.2% fatty acids in the CORN and SOY formula, respectively. The formulas or HM were fed from birth through 8 wk of age, and growth and the plasma and red blood cell (RBC) phospholipid fatty acid composition was determined at 3 d, 4 wk, and 8 wk of age. Growth did not differ among groups. The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages. Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed HM during wk 4 and 8. Plasma and RBC 22:5(n-6) was not increased in the formula groups at any age. The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants. The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than HM is unknown. The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain. PMID- 1287560 TI - Effects of a protein-rich diet during convalescence from shigellosis on catch-up growth, serum proteins, and insulin-like growth factor-I. AB - Shigellosis in children can cause growth retardation, worsening of malnutrition, and hypoproteinemia. To assess the effects of ingestion of a protein-rich diet during convalescence, 22 children aged 2 to 4 y with culture-proven shigellosis were randomly assigned after 5 d of antibiotic treatment to 21-d feeding regimens of either a 150 kcal/kg/d high-protein diet with 15% of calories as protein or an isocaloric control diet with 6% of calories as protein. At the start and end of dietary treatment, weight, height, mid-arm circumference, skinfold thickness, serum protein concentrations, and serum IGF-I were measured. Means of weight gain and increases in mid-arm circumference were greater in children fed high-protein diets than those fed control diets (1.23 versus 0.76 kg; 1.40 versus 0.96 cm; p < 0.05). Mean increase in height in children fed high-protein diets (0.83 cm) was not significantly greater than with control diets (0.74 cm). Mean increases in serum concentrations of total protein, prealbumin, and retinol-binding protein were greater in the high-protein group than in controls (p < 0.05). Mean serum concentrations of IGF-I were low in both groups before treatment [4.2 +/- 2.6 nmol/L (31.9 +/- 19.6 ng/mL) in controls; 3.1 +/- 3.4 nmol/L (24.0 +/- 26.3 ng/mL) in the high-protein group] but increased more in the high-protein group [39.0 +/- 16.2 nmol/L (298 +/- 124 ng/mL)] than in the control group [16.7 +/- 9.2 nmol/L (128 +/- 70 ng/mL), p < 0.01].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287561 TI - Energy expenditure, lipolysis, and glucose production in preterm infants treated with theophylline. AB - Theophylline is administered to preterm infants with pulmonary disease to improve pulmonary function and reduce apneic episodes. Because it potentially mediates both alpha- and beta-receptor-effector mechanisms, we tested the hypothesis that it increases lipolysis, gluconeogenesis from glycerol, and energy expenditure in 16 preterm infants, eight of whom were treated therapeutically with theophylline for apnea of prematurity (T) and eight of whom were controls (C). Mean +/- SD postnatal ages were 4.8 +/- 1.9 wk (T) and 2.4 +/- 0.9 wk (C) (p < 0.01). Corrected gestational ages were 35 +/- 1.6 wk (T) and 34 +/- 0.5 wk (C) (p = NS). Body weights were 1.69 +/- 0.13 kg (T) and 1.70 +/- 0.23 kg (C) (p = NS). All infants were clinically stable, breathing room air, fed enterally, and receiving no diuretics, steroids, or antibiotics. Lipolysis, hepatic glucose production, and gluconeogenesis from glycerol were measured using [2-13C]glycerol and [6,6 3H2] glucose tracers. Body water and energy expenditure were measured by the 2H2(18)O method. Body water volumes were 68.5 +/- 3.4% body weight (T) and 70.2 +/- 3.4% (C) (p = NS), suggesting fat was 10-13% of body weight in both groups. Mean daily energy expenditure was 65 +/- 22 kcal/kg body weight/d (T) versus 59 +/- 5 kcal/kg body weight/d (C) (p = NS). Between 4 and 6 h after a feeding, glucose production rates were 40.5 +/- 4.3 mumol/kg/min (T) and 37.6 +/- 4.8 mumol/kg/min (C) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287562 TI - Effects of an early weaning on phosphate transport maturation in the rat kidney: influence of the phosphate content of the diet. AB - The renal phosphate (Pi) transport system matures during the 3rd postnatal wk in the rat by an increase in the carrier affinity for sodium-cotransported phosphate. This study examines the ability of pups to adapt their renal Pi transport to the dietary phosphorus content during this period of carrier affinity maturation, corresponding to the weaning period in the rat. Clearance experiments and brush border membrane studies were performed on 21-d-old rats weaned early on d 16 onto a low phosphate diet (LPD, 0.19 g/100 g), a normal phosphate diet (control, 0.78 g/100 g), or a high phosphate diet (HPD, 1.5 g/100 g). In LPD rats, the Pi fractional excretion (0.3 +/- 0.1%) was lower than in controls (18 +/- 3%, p < 0.001). It remained very low (0.21 +/- 0.05% in LPD rats versus 40.5 +/- 6.3% in controls, p < 0.001) after Pi perfusion (1.5 mumol.min 1.100 g-1) and the reabsorbed Pi per min, corrected for the glomerular filtration rate, was higher than in the two other groups. The calcium fractional excretion (12.6 +/- 1.02%) in the LPD rats was much higher than in the controls (0.42 +/- 0.2%, p < 0.001). In contrast, HPD rats had an elevated Pi fractional excretion (41 +/- 4%, p < 0.001), whereas reabsorbed phosphate per min corrected for the glomerular filtration rate was not increased by a Pi load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287563 TI - Glycogenesis in the cultured fetal and adult rat hepatocyte is differently regulated by medium glucose. AB - We examined the glycogenic response to glucose in cultured fetal and adult rat hepatocytes. After a 48-h culture in Dulbecco's modified Eagle's medium, 1 mM glucose, insulin, and cortisol, cells were cultured for 4 h in serum-free medium containing glucose (1-30 mM) and U-14C-glucose. Incorporation of 14C-glucose into glycogen was greater in fetal hepatocytes compared with adult hepatocytes at all glucose concentrations (p < 0.001). Net glycogenic rate in fetal cells was greatest between 1 and 8.3 mM (7.7- +/- 1.1-fold increase) compared with a 3.8- +/- 0.6-fold increase in adult cells. In contrast, there was a 19.4- +/- 2.7-fold increase in glycogen accumulated between 8.3 and 30 mM glucose in the adult and a 1.6 +/- 0.1-fold increase in the fetus. Total glycogen synthetase activity was higher in fetal than adult hepatocytes (p < 0.001), but the active a form was similar in fetal and adult hepatocytes. Glycogen synthase a/+b was stimulated at 8.3 mM or greater glucose in fetal hepatocytes, and 5.7 mM or greater in adult hepatocytes (p < 0.05). Total phosphorylase did not change with medium glucose, but glycogen phosphorylase a/a4+b decreased in adult hepatocytes incubated in 5.7 mM glucose or greater (p < 0.05). Fetal phosphorylase a/a+b was increased at 8.3 mM or greater glucose (p < 0.05). In contrast, both adult and fetal phosphorylase were activated by glycogen. A glucose-induced increase in active phosphorylase may induce the decrease in net glycogenic rate at high glucose in fetal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287564 TI - Mitochondrial ATP-synthase deficiency in a child with 3-methylglutaconic aciduria. AB - We report the finding of mitochondrial ATP-synthase deficiency in a child with persistent 3-methylglutaconic aciduria. The child presented in the neonatal period with severe lactic acidosis, which was controlled by Na-HCO3 and glucose infusions. During the 1st y of life, there were several episodes of lactic acidosis precipitated by infections or prolonged intervals between meals. The excretion of lactate in urine was variable, but there was a persistent high excretion of 3-methylglutaconic acid. The activity of 3-methylglutaconyl-CoA hydratase in fibroblasts was normal. The child had a hypertrophic cardiomyopathy and magnetic resonance images revealed hypoplasia of corpus callosum. The gross motor and mental development was retarded, but there were no other neurologic signs. Investigation of muscle mitochondrial function at 1 y of age revealed a severe mitochondrial ATP-synthase deficiency (oligomycin-sensitive, dinitrophenol stimulated Mg2+ ATPase activity: 27 nmol x min-1 x (mg protein)-1, control range 223-673 nmol x min-1 x (mg protein)-1. The mitochondrial respiratory rate was low and tightly coupled. The respiratory rate was normalized by the addition of an uncoupler. Low Mg2+ ATPase activity was also demonstrated by histochemical methods. Morphologic examination revealed ultrastructural abnormalities of mitochondria. There was no deletion of mitochondrial DNA. The sequences of the ATP synthase subunit genes of mitochondrial DNA were in accordance with published normal sequences. PMID- 1287565 TI - A study of perceptual development for musical tuning. AB - Musical tuning perception in infancy and adulthood was explored in three experiments. In Experiment 1, Western adults were tested in detection of randomly located mistunings in a melody based on musical interval patterns from native and nonnative musical scales. Subjects performed better in a Western major scale context than in either a Western augmented or a Javanese pelog scale context. Because the major scale is used frequently in Western music and, therefore, is more perceptually familiar than either the augmented scale or the pelog scale are, the adults' pattern of performance is suggestive of musical acculturation. Experiments 2 and 3 were designed to explore the onset of culturally specific perceptual reorganization for music in the age period that has been found to be important in linguistically specific perceptual reorganization for speech. In Experiment 2, 1-year-olds had a pattern of performance similar to that of the adults, but 6-month-olds could not detect mistunings reliably better than chance. In Experiment 3, another group of 6-month-olds was tested, and a larger degree of mistuning was used so that floor effects might be avoided. These 6-month-olds performed better in the major and augmented scale contexts than in the pelog context, without a reliable performance difference between the major and augmented contexts. Comparison of the results obtained with 6-month-olds and 1 year-olds suggests that culturally specific perceptual reorganization for musical tuning begins to affect perception between these ages, but the 6-month-olds' pattern of results considered alone is not as clear. The 6-month-olds' better performance on the major and augmented interval patterns than on the pelog interval pattern is potentially attributable to either the 6-month-olds' lesser perceptual acculturation than that of the 1-year-olds or perhaps to an innate predisposition for processing of music based on a single fundamental interval, in this case the semitone. PMID- 1287566 TI - Prime time: fatigue and set effects in the perception of reversible figures. AB - Subjects viewed unambiguous versions of both stationary and rotating Necker cube illusions for varying durations prior to the presentation of the standard ambiguous figure. In each case, the subjects were more likely to report the ambiguous figure to be (1) in the same configuration as that of the preceding prime following brief preexposure periods and (2) in the opposite configuration from that of the preceding prime following long preexposure periods. In addition, the number of reversals of the figure during the test period was also strongly related to the duration of the preexposure period, with progressively fewer reversals reported following longer preexposure periods. The results are interpreted as revealing the concurrent roles of "set" effects in the brief preexposure conditions and neural fatigue effects in the long preexposure conditions. Furthermore, the ability of the proposed two-process model to integrate the myriad of empirical effects in the reversible-figure literature is emphasized. PMID- 1287567 TI - Eigenvectors of the inertia tensor and perceiving the orientation of a hand-held object by dynamic touch. AB - Subjects wielded an object, hidden from view, and reported the orientation in which the object was positioned in the hand. The object consisted of a stem with two branches forming a V attached perpendicularly to the stem's distal end. The branches were differentially weighted so that the same spatial orientation of the object was associated with different orientations of its principal (symmetry) axes or eigenvectors. Perceived orientation was found to be dependent on the eigenvectors of the object's inertia tensor, computed about the point of rotation in the wrist, rather than on its spatial orientation. The results underscore the significance of the inertia tensor to understanding the perception of spatial properties by dynamic touch. PMID- 1287568 TI - Haptic perception of object distance in a single-strand vibratory web. AB - Can humans, like other animals, perceive distance by mechanical vibrations transmitted in a solid medium? In seven experiments, subjects perceived the distances from the hand of occluded metal disks attached to a taut nylon strand. Mechanical waves were initiated at the hand by the subject or at the disk by the experimenter. The results of Experiments 1 and 2 showed that perceived distance was linearly dependent on object distance with or without practice. The results of Experiments 3 and 4 revealed an inverse dependency of perceived distance on strand tension. In Experiment 5, a constant difference in perceived distance between vertical and horizontal strand manipulations was found. The results of Experiments 6 and 7 showed that distance was perceptible when the mechanical wave was not initiated by the subject. The informational basis for this haptic spatial ability was sought in the dynamics expressed by the one-dimensional wave equation, specifically, in the constants relating strand forces to strand motions. PMID- 1287569 TI - Binocular unmasking with unequal interocular contrast: the case for multiple Cyclopean eyes. AB - Under certain conditions, the detection threshold for a sinusoidal grating embedded in a noisy background may be an order of magnitude lower when binocular cues are available than when monocular cues only are present. Such binocular unmasking occurs only when the degree of interocular disparity for the target differs from that of the background. Two classes of models have been advanced to account for such unmasking. The first assumes that orientation-specific, spatial frequency channels in each eye encode the amplitude and phase of the spatial frequency component of the pattern the channel is tuned to detect. Thus, a difference in interocular disparity between target and background could result in interocular amplitude and/or phase differences in left- and right-eye spatial frequency channels. When, however, there are no disparity differences between target and background, there will be no interocular differences in amplitude and phase in the left- and right-eye channels. In this model, then, binocular unmasking reflects the binocular system's ability to respond to interocular amplitude and/or phase differences in the patterns presented to the two eyes. In the second class of models, it is assumed that the left- and right-eye patterns are first summed to form a "Cyclopean" eye. In these models, detection depends on the effect this summation process has on the power spectrum of the summated patterns. To decide between these two classes of models, we observed the occurrence of binocular unmasking when (1) the contrast of masker and signal was varied identically in both eyes and (2) the contrast of masker and signal was varied in one eye only. Consistent with our previous research, we found that the results can be accounted for in terms of a linear summation model of binocular unmasking; the alternative interocular phase detection model was disproved. The implications of these findings for binocular contrast summation in the absence of visual noise are discussed. PMID- 1287570 TI - Stages of manual exploration in haptic object identification. AB - In a yes/no identification task using touch alone, subjects indicated whether an object belonged to a named category. Previously, we found that subjects explored in two stages--first grasping and lifting the object, then executing further exploratory procedures (Lederman & Klatzky, 1990b). We proposed that Stage 1 (grasp/lift) was sufficient to extract coarse information about multiple object properties, whereas Stage 2 was directed toward precise information about particularly diagnostic properties. In the current study, subjects were initially constrained to grasping and lifting, after which they could explore further. Accuracy was above chance after Stage 1, confirming our assumption that the grasp/lift combination was broadly useful. Stage 2 increased accuracy and confidence. It primarily elicited exploratory procedures associated with object geometry, but exploration was also influenced by diagnostic object properties. PMID- 1287571 TI - The perception of shrinking in apparent motion. AB - Apparent motion was produced using two triangular patterns of different sizes, each exposed for 100 msec, with a 50-msec interstimulus interval and 200-msec recycle interval. The triangles were aligned either on center or on the midpoints of the bases. In Experiment 1, filled, outline, and three-dot triangles were viewed over four backgrounds: a blank illuminated field, and texture gradients constructed from horizontal lines, perspective lines, or a combination of these (full texture). In Experiment 2, outline and dot triangles were presented in one of three orientations: base down, base right, and base up over a blank background. Subjects made two forced-choice responses: apparent size was categorized as shrinking or not shrinking, and apparent motion was categorized as motion in depth or motion in a fixed frontal plane. The type of alignment was the major determiner of responses. When the midpoints of the base were aligned, the predominant response described a shrinking object in a fixed position in depth. When the centers were aligned, the predominant response described an object of constant size moving in depth. PMID- 1287572 TI - The perceived strength of illusory contours. AB - Illusory contours are not well understood, partially because a lack of physical substance complicates their specification via physical standards. One solution is to gauge illusory contours with respect to luminance-defined contours, which are easily quantified physically. Accordingly, we chose a metric (perceived contrast) that expresses illusory contour strength in terms of the physical contrast of luminance-defined contours. Using this metric, adult observers adjusted the contrast of a luminance-defined contour until it matched the perceived contrast of an illusory contour. Illusory contour length, inducer size, and inducer contrast all influenced illusory contour strength. The results are adequately explained via low-level visual processes. It appears that matching paradigms can be beneficial in quantitative studies of illusory contours. PMID- 1287573 TI - Psychophysical features of the transition from pure heat perception to heat pain perception. AB - The psychophysical features of the transition from the pure heat to the heat pain range were studied in 25 healthy subjects (mean age 28.8 years). Thirty short heat stimuli from -1.6 degrees C to +1.6 degrees C relative to the pain threshold were applied to the thenar of the left hand with an apparatus containing a Peltier thermode (nine different temperatures at 0.4 degrees C intervals). The subjects rated the sensation intensity on a visual analogue scale. The resulting stimulus/sensation intensity relations could be explained equally well (same goodness of fit) by a model with a power function (PF) and by a model with two linear regression lines (TLR), one for stimulus intensities below and one for those above the pain threshold and intersecting at the pain threshold. The slopes of the TLR model were significantly larger above the pain threshold than below it. The PF model produced exponents between 1.8 and 1.9. We conclude that to describe the transition area, it is sufficient to use simple linear models for both the pure heat and the heat pain ranges. PMID- 1287574 TI - Cooperative tapping: time control under different feedback conditions. AB - The same isochronous tone sequence was presented simultaneously to two mutually isolated subjects. In half the trials, accentuation in this sequence was accomplished by doubling the duration of the first and then of every fourth tone; in the other half, by doubling the frequency of those tones. The subjects' task was to follow the rhythm of the resulting four-tone patterns by finger tapping to tone onsets. There were four auditory feedback (FB) conditions: (1) no FB; (2) FB from the subject's own motor responses; (3) "alien" FB from the motor responses of the other pair member who, in turn, was listening to FB from his/her own tapping; (4) mutually "crossed" FB, where each pair member listened to FB from the tapping of the other. Tap onsets regularly preceded stimulus onsets. The observed order of the amount of this anticipation (from least to greatest) was: (1) own FB, (2) no FB, (3) alien FB, and (4) crossed FB. No mutual dynamic influence between simultaneously performing subjects was detected. Anticipation was more pronounced for sequences that were accentuated by frequency rather than by duration changes. The type of accent also influenced timing of intertap intervals in the rhythmic patterns. For the frequency accent, regular timing was produced, whereas for the durational accent, shortening of the second and lengthening of the fourth (the last) intertap interval were observed. The presence and source of feedback as well as the character of accentuation are therefore relevant factors in the timing of auditorally controlled rhythmic motor behavior. PMID- 1287575 TI - The interaction of perceived distance with the perceived direction of visual motion during movements of the eyes and the head. AB - A horizontally moving target was followed by rotation of the eyes alone or by a lateral movement of the head. These movements resulted in the retinal displacement of a vertically moving target from its perceived path, the amplitude of which was determined by the phase and amplitude of the object motion and of the eye or head movements. In two experiments, we tested the prediction from our model of spatial motion (Swanston, Wade, & Day, 1987) that perceived distance interacts with compensation for head movements, but not with compensation for eye movements with respect to a stationary head. In both experiments, when the vertically moving target was seen at a distance different from its physical distance, its perceived path was displaced relative to that seen when there was no error in perceived distance, or when it was pursued by eye movements alone. In a third experiment, simultaneous measurements of eye and head position during lateral head movements showed that errors in fixation were not sufficient to require modification of the retinal paths determined by the geometry of the observation conditions in Experiments 1 and 2. PMID- 1287576 TI - Probability inequalities for testing separate activation models of divided attention. PMID- 1287577 TI - The nature of suffering: physical, psychological, social, and spiritual aspects. PMID- 1287578 TI - The responses of caregivers to the experience of suffering. PMID- 1287579 TI - The social construct of suffering. PMID- 1287580 TI - Therapeutic interventions for suffering: professional and institutional perspectives. PMID- 1287581 TI - The management of suffering in a nursing home: an ethnographic study. PMID- 1287583 TI - The suffering of terminal illness: cancer. PMID- 1287582 TI - Suffering in addiction: alcoholism and drug dependence. PMID- 1287584 TI - The suffering of shame and humiliation in illness. PMID- 1287585 TI - The suffering of suicide: the victim and family considered. PMID- 1287586 TI - The meaning of suffering. PMID- 1287587 TI - Suffering in silence and the fear of social stigma: survivors of violence. PMID- 1287588 TI - A theoretical and empirical review of the concept of suffering. PMID- 1287589 TI - Technologic environments as causes of suffering: the ethical context. PMID- 1287590 TI - Is our society insensitive to suffering? PMID- 1287591 TI - Suffering as contrasted to pain, loss, grief, despair, and loneliness. PMID- 1287592 TI - The influence of values and culture in responses to suffering. PMID- 1287593 TI - Marginal leakage of impregnated Class 2 composites in primary molars: an in vivo study. AB - In vivo impregnation of the cervical margin was used in an attempt to prevent leakage of class 2 composite restorations in primary molars. Examination after 18 months demonstrated clinical success of the restorations. However, the exfoliated teeth presented extensive dye penetration at the approximal margins of the restorations, suggesting that impregnation did not prevent marginal leakage. PMID- 1287594 TI - Surface roughness of polished amalgams. AB - The purpose of this project was to determine the amalgam surface roughness following finishing and polishing procedures. Nine high-copper amalgams were tested. They were hand-condensed in a 3 x 3 x 30 mm mold. Each sample was divided into four sections, and each section was finished by one of four methods: carving only; carving and then burnishing 15 minutes after carving; carving and then polishing at the prescribed times; or carving, burnishing 15 minutes after carving, and then polishing at the prescribed times. Each bar of amalgam had these surface treatments done at either 1, 3, 6, or 24 hours. The results indicated surface roughness may be more dependent on particle size, shape, and distribution of the individual high-copper amalgams than the polishing time or the surface treatment performed. PMID- 1287595 TI - Effect of air/water rinse versus water only and of five rinse times on resin-to etched-enamel shear bond strength. AB - This study compared the shear bond strength of composite resin bonded to etched, flattened enamel that had been rinsed for 0, 1, 2, 3, 5 or 20 seconds with either a water stream or an air/water spray. One hundred seventy-six molars were separated into mandibular and maxillary groups, then divided equally into 11 groups of 16 teeth each. The facial enamel surfaces were ground flat and etched for 20 seconds with 37% phosphoric acid gel. In one group, the etching gel was dried but not rinsed. In five groups the gel was rinsed with a direct stream of water at 22 psi. In the remaining five groups the gel was rinsed with an air/water spray (air at 53 psi, water at 22 psi). One tooth from each group was removed for scanning electron microscopy evaluation, leaving 15 specimens in each group for shear bond testing. Teflon tape with a 3 mm in diameter window was placed over each etched area, a light-curing liquid resin was applied and polymerized for 10 seconds, and a cylinder of light-curing composite resin was polymerized over the window. Specimens were thermocycled from 5 to 50 degrees C for 500 cycles (30-second dwell time). After 30 days' hydration at room temperature, the teeth were mounted and the composite resin cylinders were loaded in shear to failure with an Instron machine at a cross-head speed of 5 mm/min. Mean load to failure was calculated for each group. Specimens that were not rinsed had significantly (P < 0.001) less bond strength (mean 0.53 MPa) than any of the rinsed specimens (mean 18.7 MPa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287596 TI - The retention of amalgam and composite resin by a smooth, reverse-tapered pin. AB - In this study, the retention of composite resin and amalgam by a smooth, reverse tapered pin was compared to that of threaded pins. The smooth pin was significantly lower in retention than the threaded pins for each material, and caused a greater frequency of failure of the restorative material than the threaded pins. The newer smooth pin is probably not an improvement over the conventional threaded design. PMID- 1287597 TI - The effect of retention grooves on posterior composite resin restorations: an in vitro microleakage study. AB - An in vitro study was undertaken to evaluate the effect of retention grooves on the gingival marginal seal of class 2 posterior composite resin restorations when filled by the bulk and incremental techniques. Class 2 cavities were prepared in 40 extracted molar teeth. Retention grooves were prepared at the axioproximal line angles in 20 teeth. The teeth were then filled with Herculite posterior composite resin using the bulk and incremental techniques. Microleakage was assessed by radioisotope (I125) diffusion at the gingival margin, quantitatively by radiation counting on an I125 Gamma Counter and qualitatively by autoradiographs. Those class 2 cavities that were prepared with retention grooves and filled in layers showed the least radioisotope diffusion (a mean radiation count of 1588.5), while bulk insertion of the composite resin in cavities without retention grooves showed the most microleakage (mean count of 6092.4). PMID- 1287598 TI - The influence of antidepressants on aggressive behavior in stressed rats: the role of dopamine. AB - The influence of dopamine (DA) receptor blockers (haloperidol, sulpiride) on electric footshock-induced fighting behavior and on the effect of antidepressants (imipramine, clomipramine, nomifensine, mianserine) was investigated in chronically stressed male Wistar rats. Exploratory activity in an open field was measured in the same groups of animals. The effect of chronic stress and antidepressants on DA utilization in the brain was also investigated. It was shown that 48 h after the last session of repeated stress (various unpredictable stressors over 16 days) the number of fighting attacks was significantly reduced. However in stressed rats treated chronically (for 14 days) with antidepressants the intensity of fighting was restored to control value. On the contrary, when the stressed rats, receiving antidepressants chronically, were pretreated with DA receptor blockers: haloperidol (0.5 mg/kg) or sulpiride (50 mg/kg) but also alpha 1-adrenergic receptor blocker - prazosin (3 mg/kg) the effect of antidepressants was abolished. Exploratory activity was not significantly reduced under influence of stress. Neither antidepressants nor sulpiride modified exploratory activity of stressed rats. Haloperidol and prazosin but not sulpiride decreased this activity of normal, stressed and antidepressant-treated rats. It is concluded that prolonged treatment with antidepressants counteracts the decrease in aggression induced by chronic stress and that DA mechanism participate in this effect of antidepressant drugs. PMID- 1287599 TI - The responsiveness of D1- and D2-dopamine receptors in the striatum and hypothalamus of spontaneous and vasopressin hypertensive rats. AB - Low doses of apomorphine (20-50 micrograms/kg) induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein Kinases (type I inhibitor) in the striatum, anterior and posterior hypothalamus of normotensive rats by stimulating D2-dopamine receptors. In contrast, high doses of the compound (2-10 mg/kg) produced a dose dependent decrease in type I inhibitor activity. In the posterior hypothalamus of vasopressin hypertensive rats and SHR the maximal increase of type I inhibitor activity was markedly higher than in normotensive animals. Moreover, apomorphine induced the increase of type I inhibitor activity in a much wider range of doses. Only as high dose of the compound as 10 mg/kg was able to decrease type I inhibitor activity. This points to a marked supersensitivity of D2 receptors and suggests the subsensitivity of D1 receptors in this brain area of hypertensive rats. In contrast, in the striatum and anterior hypothalamus of hypertensive rats the apomorphine dose response curves were similar to those in normotensive rats. Thus, it seems tha hypertension is associated with the alteration in sensitivity of D2 and D1 receptors in the posterior hypothalamus, the brain area involved in regulation of blood pressure. PMID- 1287600 TI - Effect of captopril on serotonergic mechanisms in two-kidney, one-clip renal hypertensive rats. AB - In 2K,1C-RHR (two-kidney, one-clip hypertensive rats) serotonergic mechanisms in blood platelets were studied. The endogenous serotonin (5-HT) concentration in whole blood and in platelets remained unchanged in relation to the sham operated rats. Also the uptake of labelled 5-HT in rats with renal hypertension was not altered. However platelets aggregability was increased in 2K,1C-RHR. Acute administration of captopril (10 mg/kg and 100 mg/kg po) diminished blood pressure but did not change either the concentration of 5-HT in whole blood and in platelets of hypertensive rats or the uptake of this amine. Platelets aggregation and the amplifying effect of 5-HT in hypertensive rats were also unchanged after acute captopril administration. Similar results were observed after its administration in a dose of 30 mg/kg for one week. Our results indicate that captopril did not affect the platelets serotonergic mechanisms in 2K,1C-RHR. PMID- 1287601 TI - Adenosine receptors in basolateral membranes of rat renal cortex. AB - High affinity binding sites for adenosine were identified in rat kidney cortex basolateral membranes. Kinetic analysis indicates two sets of [3H]adenosine, [3H]ADO, binding sites, one with high affinity and Kd = 0.84 +/- 0.25 microM, one with low affinity and Kd = 4.74 +/- 0.37 microM. The ADO receptors were further characterized using ADO analogs as binding inhibitors. The most potent inhibitor of [3H]ADO binding was N-methyl-adenosine with a Kd of 5 microM, whereas 2 deoxyadenosine was about 50 times less potent. The binding of [3H]phenylisopropyladenosine, [3H]PIA, and [3H]-N-ethylcarboxamidoadenosine, [3H]NECA, to basolateral membranes was rapid and reversible. The Scatchard plot of [3H]PIA binding showed monophasic curves for experiments performed at 0 degrees C and 37 degrees C. The apparent Kd of [3H]PIA binding at 0 degrees C was 0.19 +/- 0.05 nM and 0.34 +/- 0.07 nM at 37 degrees C. The binding of [3H]NECA to basolateral membranes was found with an apparent affinity Kd of 110 +/- 50 nM at 0 degrees C. Pretreatment of membranes with N-ethylmaleimide (NEM) inhibited the [3H]PIA binding and did not affect the [3H]NECA binding. These results demonstrate that both A1 and A2 adenosine receptors are present in basolatertal membranes of rat kidney. PMID- 1287602 TI - Use of subtherapeutical dose of cisplatin and vitamin C against murine Dalton's lymphoma. AB - The antitumor activity of subtherapeutical dose of cisplatin and vitamin C combinations was studied against murine Dalton's lymphoma in vivo. The sequence dependent synergistic antitumor effect of vitamin C and cisplatin was shown to lead to the regression of the tumor resulting in a significant increase in the host survivals with tumor free hosts. Decrease in tumor pH noted in the treated tumor bearing mice and involvement of host's immune system could be an important step in this sequence-dependent antitumor activity of vitamin C and cisplatin. PMID- 1287603 TI - Synthesis and pharmacological properties of 2,4-disubstituted 5-amino-6 pyrimidinecarboxylic acid derivatives. Part II. AB - 2,4-Disubstituted 5-amino-6-pyrimidinecarboxylic acid derivatives 5-20 were synthesized and evaluated for their pharmacological activity. Compounds 11-14, 17 19 showed antiaggressive effect, compounds 5, 8, 9, 11, 12 and 19 displayed antiserotonin activity while compound 14 exerted antireserpine action. PMID- 1287605 TI - The cusp of Carabelli in Malaysians. AB - The maxillary casts of 320 Malaysian children were examined for the occurrence of the Carabelli trait on the maxillary first permanent molars. The total trait frequency was observed to be 52.2 per cent. Statistical analysis showed no sex dimorphism in the occurrence of the trait. Bilateral occurrence with a tendency towards concordance of expression between sides was also observed. PMID- 1287604 TI - Synthesis and local anesthetic and circulatory actions of aminoesters and hydroxyamine monoterpene derivatives. AB - Esters of N,N-diethylaminoacetic acid and hydroxyamines, obtained from structurally different natural monoterpenes, were pharmacologically examined. It was proved that salts of the obtained compounds had local anesthetic properties in infiltration anesthesia, compounds 9, 6 and 8 having been more potent than lidocaine. Compounds 7-9 slightly increased the arrhythmogenic dose, and compound 12 - the lethal dose of strophanthin. All the examined compounds transiently decreased the arterial blood pressure and displayed a cardiopressive activity. PMID- 1287606 TI - Double teeth--fusion or gemination? AB - Double teeth or joined teeth have been described under several different terms and the terminology is often confusing. There are several ways in which union of teeth can occur and the terms that are commonly used to describe the condition are fusion and gemination. Although primary double teeth themselves may be regarded as harmless anomalies, its presence can cause some abnormalities to occur in the permanent dentition. Therefore, early diagnosis of the anomaly is of considerable importance. PMID- 1287607 TI - Cross-cultural variations in dental knowledge among antenatal mothers. AB - This study evaluates the level of dental knowledge among 328 antenatal mothers from different ethnic groups and ascertains the importance of the various sources of dental information. The mothers were interviewed based on a structured questionnaire. Most mothers knew about the number of sets of teeth they possessed throughout their life. This was most evident among the Chinese and least among the Malays. Only 42.7% of the mothers interviewed were positive about the preservation of their teeth throughout life. This belief was highest among the Chinese followed by the Indians. However about 40% of the Chinese believed that tooth decay is hereditary. Generally the principal sources of dental information cited by most mothers were television or radio followed by dentists, school and family. This order of importance was similarly observed among the Malays and Chinese. However, among Indians, family members represent the second most important source of dental information. The implications of these findings are discussed. PMID- 1287608 TI - Understanding prevention of dental caries and gum disease in the singapore population. AB - Prevention has been recognized as a cost-effective method for the control of oral diseases. Knowledge of prevention can influence preventive dental behavior. This study surveyed knowledge on the prevention of dental caries and gum disease among a selected group of adults. Respondents were asked to indicate the importance of numerous preventive measures for prevention of both categories of oral diseases. Results showed that while respondents appropriately identified the importance of regular brushing for prevention, the role of flossing is underestimated. Similarly, there was a lack of appreciation for the value of various fluoride treatment modalities in preventing dental caries. A lack of understanding of dental sealants was also evident. It is concluded that public knowledge on prevention of dental caries and gum disease deviates greatly from current scientific information. PMID- 1287609 TI - An epidemiologic study of 70 oral cancer cases at the Institute of Dental Medicine, Yangon, Myanmar, 1985-1988. AB - This study shows that in Myanmar, South-East Asia, the prevalence of oral cancers is a serious fact as they rank fifth among all cancers being known there. On the 70 oral cancer cases reported at the Institute of Dental Medicine, Yangon, the findings stressed that most patients, male or female, came from the metropolitan division (Yangon), had smoking and chewing habits. Also most of these patients came to hospital only at the severe and late stage. It confirms us in our opinion that early diagnosis and prompt treatment are a necessity. PMID- 1287610 TI - Dens evaginatus in the Vietnamese. AB - Dens evaginatus (supernumerary cusps in premolars) were detected in 50 of 4677 Vietnamese patients examined. A systematic study including morphologic, histologic, pathologic aspects of dens evaginatus was carried out and data were compared with those given in previous reports pertaining to dens evaginatus in other Asian countries. It is expected that a better knowledge concerning this anomaly will lead to appropriate measures for prophylactic treatment of dens evaginatus. PMID- 1287611 TI - Advances in antimicrobial therapy: extended release cefaclor AF. PMID- 1287612 TI - Cefaclor AF: correlation of microbiology and clinical outcome. AB - Cefaclor is active against Haemophilus influenzae and Moraxella catarrhalis in addition to the pathogens typically susceptible to first-generation cephalosporins. Cefaclor advanced formulation (cefaclor AF) provides the opportunity for once or twice daily dosing of this agent. Clinical trials using cefaclor AF have been carried out in a number of centres on bacterial infections of the respiratory tract, the urinary tract and the skin. In vitro susceptibility tests on selected pathogens from the clinical trials were carried out according to National Committee for Clinical Laboratory Standards recommendations, generally with excellent agreement between in vitro and in vivo response. PMID- 1287613 TI - Changes in the spectrum of organisms causing respiratory tract infections: a review. AB - Over the last decade, the spectrum of organisms causing community-acquired acute lower respiratory tract infections has changed. Streptococcus pneumoniae now causes approximately 30% of outpatient acute pneumonia-less than in former decades-whereas Mycoplasma pneumoniae is found in both young and elderly patients. The Enterobacteriaceae and Staphylococcus aureus are now seen more frequently as respiratory tract pathogens in community-acquired pneumonia patients, and they are the major organisms causing pneumonia in residents of homes for the elderly or nursing homes, and in immuno-compromised patients. Agents that were previously considered non-pathogenic for the respiratory tract include serotypes of Haemophilus influenzae other than type b, H. parainfluenzae and Moraxella (Branhamella) catarrhalis; these organisms affect mainly patients with underlying cardiopulmonary disease. Legionella species can cause sporadic as well as epidemic disease of the lower respiratory tract. Chlamydia pneumoniae is a newly recognized pathogen responsible for mild to severe upper and lower respiratory tract infections. In 60-80% of cases, hospital-acquired pneumonias are caused by Gram-negative bacilli and S. aureus. These organisms colonize the mucosal membranes of the upper respiratory tract and penetrate into the lower tract by aspiration or intubation. PMID- 1287614 TI - A multicentre trial of cefaclor advanced formulation versus cefaclor in the treatment of acute bronchitis. AB - Two prospective randomized, double-blind, parallel studies were carried out in Europe to compare cefaclor advanced formulation (cefaclor AF) with cefaclor in the treatment of acute bronchitis caused by susceptible pathogens. A total of 1,321 patients suffering from acute bronchitis confirmed by clinical data and a negative chest X-ray were randomized for treatment in the two multicentre trials. Three doses of cefaclor AF were tested: 375 mg twice daily and 500 mg twice daily were compared with cefaclor 250 mg three times daily; and cefaclor AF 750 mg twice daily was compared with cefaclor 500 mg three times daily. Duration of therapy was seven days. Assessments (complete history, physical examination, sputum specimens for culture and Gram's stain, plus clinical and laboratory evaluations of safety) were carried out within 24 hours before the first dose, during therapy, within 72 hours after therapy completion and, in the 375 mg and 500 mg dose groups, 1-2 weeks after the end of therapy. There were no significant differences between the total evaluable cefaclor AF population and the total evaluable cefaclor population with regard to favourable post-therapy responses. Most favourable clinical and bacteriological response rates in the 375 and 500 mg doses were 80% or above. In the higher dose group, there was a favourable post therapy symptomatic response in 100% of evaluable patients, with favourable bacteriological responses in 93.3% patients receiving cefaclor AF and 96.8% receiving cefaclor (no significant difference). Only one serious drug-related adverse event was reported (anaphylactic reaction). Adverse events related to the digestive system were reported by 4.7% of the cefaclor AF-treated patients and 4.5% of the cefaclor-treated patients during the entire study period. Cefaclor AF, at all three dose levels studies, was seen to be as safe as cefaclor in the treatment of acute bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. PMID- 1287615 TI - Pharmacokinetics of cefaclor AF: effects of age, antacids and H2-receptor antagonists. AB - The pharmacokinetics and bioavailability of cefaclor advanced formulation (cefaclor AF) were investigated in two studies, one comparing healthy elderly and younger volunteers and the other assessing the effects of an antacid and H2 receptor antagonist on cefaclor AF bioavailability. The pharmacokinetics of a 750 mg dose of cefaclor AF were studied in 30 subjects ranging in age from 65 to 84 years and 10 control subjects 21-45 years of age. Compared with controls, elderly subjects exhibited higher plasma concentrations of cefaclor which were attributed to lower plasma clearance. There was a strong association between age and renal function, and the plasma clearance of cefaclor was highly dependent upon renal function. Thus, elderly patients with impaired renal function had a reduced ability to eliminate cefaclor. Due to a short elimination half-life and wide therapeutic index, dosage adjustments are not necessary in patients exhibiting moderate renal dysfunction. The 15 healthy men in the second trial were crossed over to receive five treatments, including cefaclor AF (500 mg) alone, cefaclor AF with or preceded by cimetidine, cefaclor AF followed by Maalox TC and cefaclor immediate release (500 mg) alone. Cefaclor AF and immediate release cefaclor had similar bioavailability, but plasma concentrations were maintained for a longer period of time when cefaclor AF was administered. Cimetidine did not alter the bioavailability of cefaclor AF but Maalox TC, coadministered with cefaclor AF, reduced the extent of absorption. This suggests that cefaclor AF bioavailability is influenced by the antacid Maalox TC but not by H2-receptor antagonist cimetidine. PMID- 1287616 TI - Cefaclor AF versus cefaclor in acute exacerbations of chronic bronchitis. AB - The effectiveness and safety of cefaclor advanced formula (AF) compared with cefaclor in the treatment of acute exacerbations of chronic bronchitis were evaluated in multicentre trials in the United States and Europe. In the US study, patients were randomized to receive either cefaclor AF 375 mg twice daily or 500 mg twice daily or 250 mg cefaclor three times daily. Three dose levels of cefaclor AF were used in the European study: 375 mg, 500 mg and 750 mg twice daily; the comparative agent was cefaclor 250 mg three times daily in the 375 mg and 500 mg strata, and cefaclor 500 mg three times daily in the 750 mg stratum. The total number of patients receiving cefaclor AF was 667 versus 357 patients receiving cefaclor. Results showed that cefaclor AF administered twice daily at 375, 500 or 750 mg was as effective as cefaclor 250 mg three times daily for the treatment of acute exacerbations of chronic bronchitis. Evaluable patients receiving cefaclor AF in the US study had a clinical response rate of over 90% and a bacteriological response rate of over 85%. In the European study, patients receiving cefaclor AF had clinical response rates over 85% and bacteriological response rates ranging from 50% to 85%. The safety profile for cefaclor AF was similar to that reported for other beta-lactam antibiotics. PMID- 1287617 TI - Possible mechanisms of action of antimicrobial agent-associated gastrointestinal symptoms. AB - Gastrointestinal symptoms, particularly diarrhoea, are a relatively common side effect of antibiotic usage. In the vast majority of cases the mechanisms involved in these side effects are not understood. Proposed mechanisms include the direct action of antibiotics on intestinal function, inducing predisposition to infection with an enteric pathogen, and factors secondary to disturbance of the normal intestinal flora that do not involve infection with a known pathogen. There is some evidence for all three potential scenarios. PMID- 1287618 TI - Cefaclor AF in the treatment of streptococcal pharyngitis/tonsillitis. AB - Two double-blind, double-dummy, randomized multicentre studies compared the safety and efficacy of 10-day regimens of cefaclor advanced formulation (cefaclor AF) (375 mg twice daily) with cefaclor (250 mg three times daily) in the treatment of proven group A beta-haemolytic streptococcal pharyngitis/tonsillitis. Of the 1,138 patients enrolled, 764 (cefaclor AF:392; cefaclor: 372) were evaluated for efficacy. All patients enrolled in the studies (570 treated with cefaclor AF and 568 treated with cefaclor) were evaluated for safety. Clinical and bacteriological evaluations were performed on treatment days 4-6, and after completion of treatment within 3-5 days and 2-3 weeks. In evaluable patients, the post-therapy clinical success and bacteriological cure rates for cefaclor AF were 96.7% and 93.6%, respectively; the rates were 98.1% and 94.1% for cefaclor. Sixteen cefaclor AF-treated patients and 14 cefaclor treated patients withdrew early from the trial because of adverse events. There were no significant differences between treatment groups in the overall number of adverse events reported. Diarrhoea was the most frequently reported adverse event (5.6%) in cefaclor AF-treated patients, and headache/migraine was the most frequently reported adverse event (5.6%) in the cefaclor-treated patients. Cefaclor AF (375 mg twice daily) is as effective and safe as cefaclor capsules (250 mg three times daily) in the treatment of streptococcal pharyngitis/tonsillitis. PMID- 1287619 TI - Ascertaining how much compliance is enough with outpatient antibiotic regimens. AB - Compliance with outpatient antibiotic regimens can now be measured by electronically monitoring the time history of dosing. This new approach reveals that many patients comply only partially with prescribed regimens in randomized, controlled, outpatient trials. Omitted or delayed doses and early cessation of dosing are commonly observed. Partial compliance converts a fixed-dose trial into a set of natural experiments in dose ranging, presenting a variety of patterns of dose timing that can be correlated with clinical outcomes for an estimate of minimum compliance needed for satisfactory outcome. Reliable measures indicate little difference in compliance between once- and twice-daily regimens, but considerably higher rates of omitted doses with three-times-daily or four-times daily dosing. A key practical issue is to ensure continuity of drug action in the face of the most common compliance errors. Continuity of action is more likely when the prescribed interval between doses is considerably shorter, preferably half or less, than the drug's duration of action, allowing doses occasionally to be delayed or omitted without a gap in drug action. Thus, a twice-daily regimen may be expected to maintain crucial continuity of drug action better than a once daily regimen, even if a few more doses are missed. Errors to avoid in compliance with outpatient antibiotic regimens are prolonged intervals between doses and early cessation of treatment. PMID- 1287620 TI - Comparative trials of cefaclor AF in uncomplicated cystitis and asymptomatic bacteriuria. AB - Two different doses of cefaclor advanced formulation (AF), a new sustained release formulation of cefaclor, were compared with the regular formulation of cefaclor for efficacy and safety in the treatment of uncomplicated cystitis and asymptomatic bacteriuria. A 7-day course of treatment was used, and the trials were double-dummy and double-blind. In one trial, cefaclor AF 500 mg once daily (at night) was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were found in 179/189 (94.7%) and 160/191 (83.8%) patients, respectively, given cefaclor AF and in 82/87 (94.3%) and 74/90 (82.2%) patients given cefaclor, 5-9 days after the end of treatment. In the other trial, cefaclor AF 375 mg twice daily was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were obtained in 164/180 (91.1%) and 156/184 (84.8%) patients, respectively, given cefaclor AF, and in 86/92 (93.5%) and 81/93 (87.1%) patients taking cefaclor, 5-9 days after the end of treatment. Very similar results were found in both studies in those patients who were assessable 3-5 weeks later. Only 4.3% and 2.4% of patients treated with cefaclor AF (375 mg and 500 mg, respectively) and 2.2% of cefaclor patients discontinued therapy due to adverse events. The three most commonly reported events were vaginal moniliasis or vaginitis (8.6%), headache (5.0%) and nausea (4.8%). No significant differences were found between clinical efficacy and safety parameters in the different study groups, and it was concluded that cefaclor AF in a twice-daily or once-daily dosage is as effective and as safe as the currently recommened three-times-a-day dosage of cefaclor. PMID- 1287621 TI - Broad- versus narrow-spectrum antibiotic use: the role of in vitro testing and its correlation with clinical efficacy. AB - The spectrum of activity of any antibiotic varies with time, the geographical locale and the site of isolation of the bacteria. This variability is related to the changing heterogeneity (specifically, the degree of resistance) of the bacterial population. In order to choose the most appropriate antimicrobial agent, it is necessary to know the infection site, the degree of diffusion of antibiotics at this site, and the pathogen responsible, and then to determine the sensitivity of the pathogen. If the pathogen is unknown, an assessment of the patient's clinical status should be made; generally, the weaker the patient, the broader the spectrum of antibiotics that should be used. If the pathogen and its in vitro susceptibility pattern are known, narrow-spectrum antibiotics are preferable. The carefully standardized conditions of in vitro testing do not correlate with the in vivo situation, in which the effectiveness of antibiotics is altered by diffusion and immune response. The in vitro tests available do not always correlate with the clinical situation; some bacteria showing resistance in the laboratory are actually susceptible in practice in some infection sites, and vice versa. In vitro tests are also affected by technical limitations. An in vitro test can aid the assessment of efficacy but cannot guarantee it. PMID- 1287622 TI - Comprehensive safety profile of cefaclor AF in respiratory, urinary tract and skin infections. AB - The safety of cefaclor advanced formulation (cefaclor AF) was evaluated in 3,272 patients participating in 11 controlled clinical trials in comparison with cefaclor (2,210 patients) for a variety of infectious illnesses. Daily doses of cefaclor AF ranged from 500 to 1500 mg, with a mean duration of treatment of 8.1 days (range 1-18 days). There were no significant differences between the cefaclor AF- and cefaclor-treated groups in the frequency of adverse events by body system for all events reported. The majority of adverse events related to therapy were mild and transient. Severe adverse events occurred in 2.1% of the cefaclor AF group and 2.7% of the cefaclor group. The most frequently reported adverse events for cefaclor AF were diarrhoea (3.4%), headache (3.2%), nausea (2.5%) and vaginal moniliasis (2.5% of females). Drug-related adverse events led to early discontinuations in 1.7% of cefaclor AF-treated patients and 1.6% of cefaclor-treated patients. Overall, there were few significant differences in the frequency of adverse reactions between older and younger patients. Notably, elderly patients reported significantly less diarrhoea and fewer hypersensitivity type reactions. There were, however, more therapy discontinuations due to adverse effects in patients aged 65 years or older than in those less than 65 years of age. Many of the discontinuations were thought to be unrelated to therapy. Alterations in laboratory values in patients treated with cefaclor AF were similar to those seen with other beta-lactam antibiotics. The comprehensive data indicate that cefaclor AF is a safe therapeutic option for a variety of common bacterial infections. PMID- 1287623 TI - Naming of dopachrome conversion factor (DCF) PMID- 1287624 TI - Measurements of light transmission through single melanophores. AB - A photometrical method has been developed that allows assessment of subcellular pigment migration in melanophores of the fish cockoo wrasse (Labrus ossifagus L.) The pigment migration was studied with local light spot transmission measurements. Depending on where the light beam is placed on the melanophores it is possible to study events within an area of approximately 75 microns 2. Measuring pigment translocation in different parts of a melanophore gives new possibilities to study how cell membrane receptor-mediated signals are spread within a single cell, which will increase our understanding of how receptor activating drugs exert their cellular effect. The technique can be used in pharmacological and biophysical studies and in biosensors, pharmaceutical screens, environmental detectors, etc. The method clearly has the ability to study local and small changes in light transmission due to displacement of melanophore pigment granules. Since one melanophore on the tip of an optical fibre would be enough to obtain a measurable effect, the presented technique provides the basis for future development of biosensors small enough for in vivo applications, e.g., to monitor the catecholamine levels of circulating blood. PMID- 1287625 TI - Extracellular matrix constituents and pigment cell expression in primary cell culture. AB - Three types of pigment cells were isolated and cultured from larval Rana pipiens, and their attachment, maintenance, and proliferation were examined in the presence of extracellular matrix constituents (ECMs) in primary cell culture. The initial profile of pigment cell types present on day 2 of culture reflects the relative attachment of the cells to the dishes. Changes in the numbers of cells present after day 2 reflects the influence of factors present in the culture media on the maintenance, proliferation, or detachment of each type of pigment cell. Fetal bovine serum (FBS) promoted melanophore expression, but inhibited iridophore expression. FBS had no effect on xanthophores. In contrast, ventral skin conditioned medium (VCM), which contains melanization inhibiting factor, strongly stimulated iridophore expression, while it markedly inhibited melanophore expression. VCM had little effect on xanthophores. Of the ECMs tested, collagen type I had no effect on pigment cells. Fibronectin slightly inhibited melanophore expression, while it moderately stimulated iridophores and xanthophores. The stimulatory effect of fibronectin was not as strong as that of FBS or VCM. Laminin was also tested; however, it did not allow pigment cells to attach to the dishes, at least under the culture conditions utilized. The results of these experiments are discussed in terms of the general mechanisms of pigment pattern formation. PMID- 1287626 TI - Melanin standard method: titrimetric analysis. AB - Melanin isolated from the ink sac of Sepia officinalis (Sepia melanin) has been proposed as a standard for natural eumelanin, and a standard mild isolation and purification protocol for Sepia melanin has been developed (Zeise, doctoral dissertation, Johns Hopkins University, 1991). The goal of the present work, developed using Sepia melanin, was to quantify the bioavailable carboxylic acid groups present in melanin particles. Bioavailability is governed by the accessibility of carboxy groups to the surrounding biological milieu, and is expressed as microequivalents of carboxy group per gram of melanin. The present work was carried out using an heterogeneous slurry of melanin in a nonaqueous system. A standard acidic titrant, and an automatic titrator operating in an equilibrium titration mode were used to characterize and quantify the carboxy group content of Sepia melanins and several other commonly used melanins purified by a standard method (Zeise et al., Pigment Cell Res. [Suppl] 2:48-53, 1992). PMID- 1287627 TI - Melanin standard method: empirical formula 2. AB - Natural melanins are composed of two distinct portions; a protein fraction and a chromophoric backbone. There is no unequivocal evidence for covalent bonding between these two fractions, and standard protocols used in protein purification have failed to separate the protein fraction from the chromophoric fraction. In order to study the chromophoric backbone, many workers have resorted to harsh isolation and purification protocols that are now known to degrade and damage the chromophoric portion. These artifactual melanin preparations are poor models for valid chemical, physical, and biological studies. We have developed a mild isolation and purification protocol for melanins that takes into consideration both the particulate nature of natural melanins and the stability characteristics of the chromophoric fraction. Mathematical factoring of the quantitative amino acid data into the elemental analysis was used to obtain the empirical formula of the chromophoric backbone of melanins. The analyses have shown that melanins from various sources have significantly different amino acid compositions and contents, molar C/N ratios, and empirical formulae. This method successfully differentiates melanins from a variety of sources, namely, human hair, Sepia officinalis, Sigma Chemical Company (cat. no. M8631), autoxidation of dopa, and from the feathers of Rhode Island Red chickens. Analytical results from these studies are presented and discussed. PMID- 1287628 TI - Morphological and biochemical characterization of the cream markings in the integument of the female isopod, Armadillidium vulgare. AB - Cream markings aligned along the dorsal region of the female isopod, A. vulgare, were investigated with light and a fluorescence microscope and an electron microscope. Biochemical studies were also carried out. The cream markings were observed in the dorsal integument as a group of cream-colored chromatophores that emit a yellow fluorescence. These chromatophores, which are distinguishable from ommochrome chromatophores, contained numerous granules in the cytoplasm, and these granules (0.6-3.0 micron in length by 0.4-1.5 microns in width) were electron-lucent and spheroidal in shape with a concentric arrangement of membranes. Based on various biochemical analyses, the principal component of the yellow pigment isolated from the cream markings was identified as sepiapterin. These facts revealed that the cream markings are the chromatophores that contain pteridine granules. The males have no cream markings like those of the females, since the cream-colored chromatophores are externally hidden by the ommochrome chromatophore layer. The content of sepiapterin in the males was about two times greater than that in the females. This quantitative difference in sepiapterin content between males and females suggests that the pteridine formation in this pigment cell may be regulated by hormones associated with sex determination. PMID- 1287629 TI - [Ethnomedical and transcultural psychiatric aspects of migration]. AB - In consideration of the current socioeconomical and political development in the world a dramatic increase of migration streams are expected. Migrant families are always a new phenomenon on both sides in host countries. One important root of these specific problems are: Culture-conditioned differences concerning value orientation between immigrants of several ethnics on one hand and the resident population on the other hand, but also among the immigrants of several ethnic groups themselves. These differences of the value orientation, of course, also refer to the illness concepts, the illness behavior as well as utilization of assistance among the several sectors of the Health Care Systems. It is expected that the professional sector of the Health Care Systems in the host countries will be confronted massively with ethnomedical and transcultural-psychiatric aspects of migration in the future. An adequate medical care of the migrants (especially concerning psychiatric disorders) will only be possible in case of an appropriate consideration of such culture-bound peculiarities. PMID- 1287630 TI - [Psychosocial stress factors in the historical transition]. AB - More and often in our consultations we have seen that parents as well as children and adolescents attribute psychosomatic disorders and learning and behavioural disturbances to altered conditions caused by political changes. Interrogating 277 pupils of the 7th to 11th class in the combined Junior/Senior High School of Erfurt, we wanted to answer the question, to what extent changes caused by the new era have influenced the emotional stress loads of average adolescents. It could be concluded that two thirds of the pupils questioned can compensate very well for the stress situations that are associated to social reforms. However about one third of the children and adolescents are strongly stressed and have developed learning problems, behaviour problems and/or psychosomatic disorders. Most stress factors manifest in the family situation. The disconcertion of parents and the associated deterioration of the family's emotional atmosphere were stated as the essential factors. PMID- 1287631 TI - [Manifestation of psychiatric disorders caused by stress factors of the historical transition in former East Germany]. AB - We analysed the case histories of 149 patients who had been given hospital treatment for psychic disorders. Among them we found nine patients (6%) with stress factors caused by the radical historical upheavals in the former GDR, which had played a main role in the pathogenesis of the psychic disorders. In these cases it was above all stress factors which indirectly affected the child through the family situation. PMID- 1287632 TI - [Transcultural problems of child and adolescent psychiatry or sequelae of inverse migration? On diagnosis and treatment of children and adolescents of former East Germany in West Germany of the past]. AB - Against a background discussion whether there has been a different cultural development within the two former German states, the question is raised, whether this possible difference could lead to different influences on psychiatric illness among children and adolescents. Problems in ethnological research in general together with problems found within cross cultural psychiatry are discussed. A study of a group of 19 children and adolescents, presenting at a psychiatric clinic with the historically significant if not seldom experience of inverse migration is described. From this population only n = 4 children appeared to be significantly affected by their new surroundings. It is proposed that further investigations is needed to ascertain whether the experience of inverse migration does indeed constitute a psychological stress for children and adolescents from the former GDR. PMID- 1287633 TI - [Some impressions of child and adolescent psychiatric management in Berlin after the fall of the wall]. AB - The fall of the Berlin wall caused a sudden increase in migration from East Germany to West-Berlin. In our sample we compared 155 Berlin elementary school children to 17 children from East-Germany now living in Berlin and 25 immigrant children most oft them coming from Turkey and Poland. Although many authors expected short-term disorders of adaptation, we found a constancy of psychiatric diagnosis in the migration group. We noticed important differences particularly in the new psychosocial situation of the former East German mothers, with many single-mother-families, where the mothers now were often unemployed. PMID- 1287634 TI - [Inpatient and partial hospitalization facilities for child and adolescent psychiatry in the unified Germany, 1991]. AB - First results of the project "Surveys regarding the structure of psychiatric institutions for children and adolescents in the Federal Republic of Germany" are described. On July 1, 1991 there were 111 in-patient institutions with a total capacity for 6363 children and youths. The contributing shares of each state (Bundesland) vary enormously. The number of accommodations per 100,000 residents is between 2.1 and 19. One reason for this discrepancy lies in the fact that the services of the institutions are called upon without regard to the state borders. More important though is the fact that in the new states the psychiatric institutions for children and youths also treat young patients who are psychologically or mentally handicapped with neuropsychiatric complications to a greater extent than comparable institutions in the old states. PMID- 1287635 TI - Trisomy 16 confined to the placenta. AB - Two cases with trisomy 16 confined to the placenta are presented. Prenatal diagnosis was indicated because of fetal growth retardation. In case 1, a phenotypically normal but small-for-date boy was born. In case 2, the fetus turned out to be triploid on cordocentesis. In both instances the trisomy 16 was recovered from the placenta. Recovery indicates that the abnormality was present in the placenta during the time of fetal growth retardation, which supports an aetiological relationship. Strict appliance of the current models cannot readily explain the observed discrepancies. In case 2, a chimeric placenta as a result of a vanishing twin is assumed. Cases of placental trisomy 16 published after 1988 are reviewed. It is concluded that confined placental trisomy 16 can cause intrauterine growth retardation if present in both the direct preparation and the villus culture. The chances of finding a chromosomally abnormal fetus (mosaic trisomy 16, triploidy) after diagnosis of trisomy 16 in chorionic villi are low but warrant further investigations. PMID- 1287636 TI - The outcome of pregnancy and prenatal chromosomal diagnosis of fetuses in couples including a translocation carrier. AB - In order to evaluate the relation between chromosomal translocation and the outcome of pregnancy, 50 couples were examined. Subjects consisted of 35 couples that included a reciprocal translocation carrier; 13 included a Robertsonian translocation carrier and 2 included a carrier of a mosaic reciprocal translocation. The reasons for performing chromosomal examinations were mainly infertility and abnormality of neonates. The rates of miscarriages and neonatal abnormalities in prior pregnancies were significantly higher than the birth rate of morphologically normal newborns. The presence of a translocation is closely related to reproductive failure because of the chromosomal imbalance. However, prenatal chromosomal examination after the 15th gestational week in subsequent pregnancies revealed that almost half of the fetuses showed normal karyotypes and only 12.8 per cent of the fetuses showed a chromosomal imbalance. Many chromosomally imbalanced fetuses are spontaneously aborted before amniocentesis. The risk of chromosomal imbalance is relatively low in prenatal diagnosis, but partial trisomies of small rearrangements tend to be preserved. PMID- 1287637 TI - Fetal presentation of Morquio disease type A. AB - A fetus with mucopolysaccharidosis type IV A (Morquio type A) is described. The family had one affected child exhibiting symptoms of classical Morquio A disease, and late in the subsequent pregnancy prenatal diagnosis was requested. At 23 weeks' gestation, moderate ascites was detected by detailed ultrasound scan and keratan sulphate was found in the amniotic fluid. The pregnancy was terminated by prostaglandin induction and the diagnosis of mucopolysaccharidosis type IV A was confirmed by demonstration of a deficiency of N-acetylgalactosamine-6-sulphate (GalNac-6-S) sulphatase in cultured amniotic cells and in post-mortem fibroblast cultures. The activities of beta-galactosidase and arylsulphatase A were normal, ruling out Morquio disease type B and multiple sulphatase deficiency. These results indicate that mucopolysaccharidosis IV A (a disease that predominantly affects the skeletal system) may produce ascites in the fetus to such an extent that it can be detected by ultrasound. PMID- 1287638 TI - Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age. AB - One hundred and fifty-one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy. PMID- 1287639 TI - Mucolipidosis type IV: accumulation of phospholipids and gangliosides in cultured amniotic cells. A tool for prenatal diagnosis. AB - Cultured amniotic fluid cells from two mucolipidosis type IV (MLIV)-affected fetuses demonstrated accumulation of phospholipids and gangliosides when compared with normal controls. Like cultured skin fibroblasts from MLIV patients, cultured amniotic cells from the affected fetuses accumulated primarily lyso phospholipids and this could be demonstrated by radioactive labelling with appropriate precursors, either inorganic phosphate or oleic acid. Furthermore, like cultured skin fibroblasts, there was significant retention of exogenously supplied GD1A ganglioside in the affected amniotic cells. This storage was previously demonstrated to be unique to MLIV and thus can be used at present as a specific procedure for prenatal diagnosis of MLIV. PMID- 1287640 TI - Prenatal diagnosis of distal arthrogryposis type I by ultrasonography. AB - Two consecutive pregnancies in a woman with initially undiagnosed type I distal arthrogryposis (DA) are reported. A prenatal diagnosis of the condition was made by ultrasound in the 17th week of gestation in one of the pregnancies, whereas in the subsequent pregnancy the disorder was excluded as early as 13 weeks' gestation. The diagnoses were verified at birth. The feasibility of prenatal diagnosis of DA type I in the second trimester is thus confirmed and its possibility in the late first trimester is suggested. PMID- 1287641 TI - Prenatal diagnosis of Huntington's disease (HD): experiences with six cases and PCR. AB - In the course of a 2-year predictive testing programme for Huntington's disease (HD), six couples from a total of 52 applicants requested prenatal testing. In each case, the pregnancy was in the first or second trimester when the couples were referred for DNA diagnosis. In five cases, exclusion testing was offered; in one case, a person at risk with an increased risk of being a gene carrier requested prenatal diagnosis. In all cases, informative markers for prenatal testing could be determined. Whenever possible, the newer technique of polymerase chain reaction (PCR) for D4S125 was applied to perform rapid prenatal diagnosis. Two couples withdrew before chorionic villus sampling was undertaken; prenatal diagnosis was completed in the remaining four cases. After exclusion testing, two pregnancies were determined to have an increased risk and two fetuses to have a low risk of being HD gene carriers. PMID- 1287642 TI - Second-trimester cancer antigen 125 and Down's syndrome. AB - This study explores if assay of cancer antigen 125 (CA 125) in maternal serum might aid the detection of Down's syndrome in the second trimester of pregnancy. CA 125 levels were determined retrospectively in stored maternal serum samples from ten Down's syndrome pregnancies and 78 controls matched for gestational and maternal age. In addition, second-trimester amniotic fluid samples from nine Down's syndrome and 109 unaffected pregnancies were analysed for CA 125. Maternal serum CA 125 values for Down's syndrome pregnancies were lower, with the median being 0.72 multiples of the unaffected population median. The medians for affected and unaffected pregnancies did not differ significantly and there was a considerable overlap in the range of values of cases and controls. The distribution of amniotic fluid CA 125 levels for Down's syndrome pregnancies resembled that for controls. From our present results, we could not find an association between Down's syndrome and second-trimester maternal serum or amniotic fluid CA 125 levels. PMID- 1287643 TI - Prenatal detection of multiple copies of a familial supernumerary marker chromosome. AB - Direct preparations and long-term cultures from a chorion villus biopsy, taken because of a known maternal additional marker chromosome, showed a 48,XX,+mar,+mar karyotype in all cells examined. The same karyotype was revealed in a subsequent amniotic fluid sample and in cord blood at delivery. Detailed examination of the child at delivery and at 1 year of age showed no evidence of phenotypic abnormality or developmental problems. PMID- 1287644 TI - Porencephalic cyst after chorionic villus sampling. PMID- 1287645 TI - Prenatal diagnosis of tetrasomy 12p by in situ hybridization: varying levels of mosaicism in different fetal tissues. AB - Prenatal diagnosis of tetrasomy 12p is complicated by the discrimination of the 12p isochromosome from the duplication 21q as well as the level of mosaicism demonstrated in the particular tissue sampled. In this disease, a high percentage of chromosomally abnormal cells are generally found in fibroblastic cells, but lymphocyte karyotypes from the same individual may be normal. We report on the pregnancy of a 37-year-old female who presented to our centre at 16 weeks' gestation for genetic amniocentesis. Sonography of the fetus revealed dextrocardia and diaphragmatic hernia. Chromosome analysis of amniocytes demonstrated mosaicism of a 47,XY,+i(12p) line in 80 per cent of cells and a normal male line (20 per cent), consistent with the Pallister-Killian syndrome. Following termination, a 220 g male fetus of 18 weeks was examined. A flattened nose and low-set ears were noted. In situ hybridization with a chromosome 12 centromeric probe in lymphocytes and skin cells unequivocally confirmed the karyotype and showed the presence of a single centromere in the abnormal chromosome, suggesting a true isochromosome. Chromosome analysis of various fetal tissues was performed and the following percentages of abnormal cells were found: skin 100 per cent, chorion 50 per cent, placenta 30 per cent, and blood 80 per cent. The high frequency of tetrasomic cells in fetal blood at this early gestational age is noteworthy, since most reports of this syndrome show a very low percentage of abnormal cells postnatally. PMID- 1287646 TI - Prenatal diagnosis of Pallister-Killian syndrome: resolution of cytogenetic ambiguity by use of fluorescent in situ hybridization. AB - We report a case of Pallister-Killian syndrome initially diagnosed prenatally as tetrasomy 21. A 33-year-old primiparous woman was noted at 24 weeks' gestation to have moderate polyhydramnios. Ultrasonography showed diminished fetal stomach filling, hydronephrosis, and prominence of the cisterna magna. Cytogenetic analysis of cultured amniocytes was initially interpreted as mosaic tetrasomy 21: 46,XX/47,XX,+i(21q). The patient was then referred to our centre for genetic counselling. At 34 weeks' gestation, a dysmorphic infant was delivered and died within 30 min. Physical features were consistent with the Pallister-Killian syndrome. Renal, gastrointestinal, and central nervous system anomalies were found at post-mortem examination. Analysis of peripheral lymphocytes revealed 5 per cent of cells with a marker chromosome, while 92 per cent of cultured fibroblasts had this same marker. Fluorescent in situ hybridization (FISH) using an alpha-satellite probe for chromosomes 13 and 21 failed to hybridize to the marker, while a chromosome 12 centromeric probe unequivocally identified it as an i(12p). Use of FISH can provide rapid, specific prenatal diagnosis of ambiguous marker chromosomes and improve prenatal counselling. PMID- 1287647 TI - Fetal granulocytes in maternal venous blood detected by in situ hybridization. AB - Fetal male cells from maternal venous blood were detected by a non-radioactive in situ hybridization method using the biotinylated Y-specific DNA probe pY431. The hybridizations were performed on Ficoll-Paque-isolated nucleated blood cells obtained from 11 pregnant women in the seventh to 31st week of gestation. A Y specific signal was detected in both granulocytes and lymphocyte-like cells in seven of the 11 women studied. These women gave birth to boys. In one of the four remaining cases, a Y-specific signal was detected in the lymphocyte-like cells but not in the granulocytes. This woman gave birth to a girl. The other three women had no cells with a Y-specific signal and all three gave birth to girls. Altogether, 83,500 nucleated cells were analysed. One hundred and three cells showed a Y-specific signal. Of these Y-specific cells, 62 per cent were granulocytes and 38 per cent lymphocyte-like cells. Our results suggest that fetomaternal transfer of granulocytes is common and that it occurs as early as in the seventh week of gestation. None of the ten non-pregnant female control samples showed positive cells with the Y-chromosome-specific probe; approximately 97 per cent of the cells from the five adult male controls showed a Y-specific signal. Our results indicate that in situ hybridization using a Y-specific DNA probe performed on granulocytes in maternal blood can be used for fetal male sex determination. PMID- 1287648 TI - Preparation of ferric adsorbent paper and its interaction with phosphate containing biomolecules. AB - A procedure for the synthesis of a selective adsorbent for phosphate-containing biomolecules is described. The sorbent is based on Whatman chromatography paper, which is activated with epichlorohydrine, followed by the coupling of iminodiacetic acid to the active surface of the sorbent. The immobilized complex forming chelating groups are saturated with ferric ions. The synthesized adsorbent is a counterpart to Chelating Sepharose and makes it possible to extend the use of immobilized ferric chelating groups for analytical purposes. It displays a high affinity towards compounds containing free terminal phosphate groups (phosphopeptides, nucleotides). The results of the binding experiments are compared to the corresponding data obtained with Chelating Sepharose gels. PMID- 1287649 TI - Purification of the neurite outgrowth promoting fragment of mouse laminin. AB - A method for isolation of the neurite outgrowth promoting fragment of mouse laminin (fragment 8) is described in this paper. Besides producing excellent yields, this method was shown to be fast and practical, since it is based on a single step which consists in an ion exchange chromatography of elastase digested laminin. PMID- 1287651 TI - Molecular surface area and hydrophobic effect. PMID- 1287650 TI - Purification of rat urinary kallikrein: comparative studies with rat submandibular gland kallikrein-like serine protease. AB - A 427-fold purification of rat urinary kallikrein (RUK) was achieved in three steps involving chromatography on columns of DEAE-Sepharose CL-6B, gel filtration on Sephadex G-100 and affinity chromatography on a column of benzamidine Sepharose. Purified enzyme showed a single band on SDS-PAGE with an estimated molecular weight of 43,000. The amino-terminal sequences of the first 25 residues of RUK resemble the reported sequence for true kallikrein and share 80% identity with rat submandibular gland (RSMG) kallikrein-like serine protease. The RUK is highly reactive towards kallikrein substrates Bz-pro-phe-arg-pNA and DL-val-leu arg-pNA, and plasmin substrate D-val-leu-lys-pNA. RSMG enzyme is more reactive towards Bz-val-gly-arg-pNA and tosyl-gly-pro-arg-pNA, preferential chromogenic substrates for trypsin-like proteases and thrombin, respectively. Both leupeptin and aprotinin inhibit RUK strongly, but soy bean trypsin inhibitor has no effect on this enzyme. RSMG enzyme is poorly inhibited by any of these inhibitors. The data suggest that although both enzymes are members of tissue kallikrein multigene family, urinary enzyme is a true kallikrein and RSMG enzyme is a kallikrein-like serine protease with different substrate specificity. PMID- 1287652 TI - Hydration of amino acid side chains: dependence on secondary structure. AB - Energy calculations have been used to study the hydration sites around the polar groups of serine, threonine and tyrosine side chains. These hydration sites depend not only on the hybridization of the polar group but also on the local secondary structure, the chi 1 side chain torsion angle and the position of the hydroxyl hydrogen atom. For tyrosine side chains, two solvent sites are found approximately in the plane of the ring. Even for serine and threonine side chains only two minimum energy sites are found in general of which one is in an expected position within hydrogen bonding of the hydroxyl hydrogen atom (unless this is blocked from interaction with solvent molecules by, for example, Oi-4 or Oi-3. The position of the second of these sites depends not only on the position of the hydroxyl oxygen but also on neighbouring main chain atoms to which it can also hydrogen bond. There is good agreement with the solvent distributions obtained from crystallographic data. PMID- 1287653 TI - Quantile distributions of amino acid usage in protein classes. AB - A comparative study of the compositional properties of various protein sets from both cellular and viral organisms is presented. Invariants and contrasts of amino acid usages have been discerned for different protein function classes and for different species using robust statistical methods based on quantile distributions and stochastic ordering relationships. In addition, a quantitative criterion to assess amino acid compositional extremes relative to a reference protein set is proposed and applied. Invariants of amino acid usage relate mainly to the central range of quantile distributions, whereas contrasts occur mainly in the tails of the distributions, especially contrasts between eukaryote and prokaryote species. Influences from genomic constraint are evident, for example, in the arginine:lysine ratios and the usage frequencies of residues encoded by G + C-rich versus A + T-rich codon types. The structurally similar amino acids, glutamate versus aspartate and phenylalanine versus tyrosine, show stochastic dominance relationships for most species protein sets favoring glutamate and phenylalanine respectively. The quantile distribution of hydrophobic amino acid usages in prokaryote data dominates the corresponding quantile distribution in human data. In contrast, glutamate, cysteine, proline and serine usages in human proteins dominate the corresponding quantile distributions in Escherichia coli. E. coli dominates human in the use of basic residues, but no dominance ordering applies to acidic residues. The discussion centers on commonalities and anomalies of the amino acid compositional spectrum in relation to species, function, cellular localization, biochemical and steric attributes, complexity of the amino acid biosynthetic pathway, amino acid relative abundances and founder effects. PMID- 1287654 TI - Relationships between sequence and structure for the four-alpha-helix bundle tertiary motif in proteins. AB - The sequences of four-alpha-helical bundle proteins are characterized by a pattern of hydrophilic and hydrophobic amino acids which is repeated every seven residues. At each position of the heptad repeat there are specific constraints on the amino acid properties which result from the topology of the tertiary motif. These constraints give rise to patterns of amino acid distribution which are distinct from those of other proteins. The distributions in each of the heptad positions have been determined by a statistical analysis of structural and sequence data derived from seven families of aligned protein sequences. The constitution of each position is dominated by a very small number of different amino acids, with the core positions consisting overwhelmingly of Leu and Ala. The positional preferences of the individual amino acids can be generally interpreted in terms of residue properties and topological constraints. The potential for four-alpha-helix bundle folding is reflected primarily in the pattern of residue occurrence in the heptad and not in the overall amino acid composition of the protein. Possible applications of this analysis in structure predictions, sequence alignments and in the rational design and engineering of four-alpha-helical bundle proteins are discussed. PMID- 1287655 TI - Free energy perturbation study on a Trp-binding mutant (Ser88-->Cys) of the trp repressor. AB - The Ser88-->Cys mutant of the trp-repressor showed a lower affinity for the corepressor than the wild-type repressor [delta delta G = 1.7 +/- 0.3 kcal/mol, Chou and Matthews (1989) J. Biol. Chem., 264, 18314-18319]. A molecular dynamics/free energy cycle perturbation study was performed to understand the origin of the decreased affinity. A value (delta delta G = 1.58 +/- 0.28 kcal/mol) comparable with the experimental value was obtained by the simulation. Free energy component analysis revealed that destabilization of the van der Waals interaction between Ser88 and Trp109 (corepressor) mainly contributed to the decreased affinity of the mutant. The rotational transition of the hydroxyl (sulfhydryl) group of Ser88 (Cys88) during the simulations affected the contributions of Arg84 and water to the free energy change in the aporepressor and those of Arg84 and Trp109 to that in the holorepressor. However, the contributions from different residues compensated each other, and the total free energy changes were almost invariable in the various simulations. PMID- 1287656 TI - Single amino acid substitutions can further increase the stability of a thermophilic L-lactate dehydrogenase. AB - Lactate dehydrogenases are of considerable interest as stereospecific catalysts in the chemical preparation of enantiomerically pure alpha-hydroxyacid synthons. For such applications in synthetic organic chemistry it would be desirable to have enzymes which tolerate elevated temperatures for prolonged reaction times, to increase productivity and to extend their applicability to poor substrates. Here, two examples are reported of significant thermostabilizations, induced by site-directed mutagenesis, of an already thermostable protein, the L-lactate dehydrogenase (EC 1.1.1.27, 35 kDa per monomer subunit) from Bacillus stearothermophilus. Thermal inactivation of this enzyme is accompanied by irreversible unfolding of the native protein structure. The replacement of Arg171 by Tyr stabilizes the enzyme against thermal inactivation and unfolding. This stabilizing effect appears to be based on improved interactions between the subunits in the core of the active dimeric or tetrameric forms of the enzyme. The thermal stability of L-lactate dehydrogenase variants with an active site Arg residue, either in the 171 (wild-type) or in the 102 position, is further increased by sulfate ions. The two stabilizing effects are additive, as found for the Arg171Tyr/Gln102Arg double mutant, for which the stability of the protein in 100 mM sulfate solution reaches that of L-lactate dehydrogenases from extreme thermophiles. All mutant proteins retain significant catalytic activity, both in the presence and absence of stabilizing salts, and are viable catalysts in preparative scale reactions. PMID- 1287657 TI - Analysis of several key active site residues of ricin A chain by mutagenesis and X-ray crystallography. AB - Active site residues of ricin A chain were analyzed by site-directed mutagenesis and X-ray diffraction to help assess their roles in the mechanism of action of this toxic N-glycosidase enzyme. Arg180 is thought, from X-ray studies, to protonate the adenine substrate at N3; this facilitates bond cleavage and is crucial to the mechanisms of action. The residue was converted to Gln and initial rate data measured. Km for the mutant is not significantly affected, increasing only 2-fold. The kcat, however, is decreased approximately 1000-fold. This is consistent with a simple interpretation that Arg180 is involved more in transition state stabilization than in substrate binding. Tyrosines 80 and 123 are known from X-ray models to stack on either side of the substrate adenine ring. When they were each converted to serine overall activity was reduced 160- and 70-fold respectively against ribosomes from Artemia salina. These effects are each approximately 10 times greater than when the residues were previously converted to phenylalanines. Sufficient protein for the Tyr80 to Phe mutant was obtained to carry out an X-ray analysis. Together with mutagenesis data, the structure suggests that the invariance of the two active site Tyr residues is largely caused by structural stability. PMID- 1287658 TI - Triple point mutation Asp10-->His, Asn101-->Asp, Arg148-->Ser in T4 phage lysozyme leads to the molten globule. AB - The triple amino acid replacement (Asp10-->His, Asn101-->Asp, Arg148-->Ser) in T4 phage lysozyme was carried out by site-directed mutagenesis. At acid pH (2.7) the mutant is in a conformational state with the properties of the molten globule: (i) the mutant protein molecule is essentially compact; (ii) its CD spectrum in the near UV region is drastically reduced in intensity as compared with the wild type protein spectrum; (iii) the CD spectrum in the far UV region indicates the presence of pronounced secondary structure in the mutant; (iv) unlike the wild type protein the mutant protein can bind the hydrophobic fluorescent probe, ANS. PMID- 1287659 TI - Probing the role of threonine and serine residues of E. coli asparaginase II by site-specific mutagenesis. AB - Site-specific mutagenesis has been used to probe amino acid residues proposed to be critical in catalysis by Escherichia coli asparaginase II. Thr12 is conserved in all known asparaginases. The catalytic constant of a T12A mutant towards L aspartic acid beta-hydroxamate was reduced to 0.04% of wild type activity, while its Km and stability against urea denaturation were unchanged. The mutant enzyme T12S exhibited almost normal activity but altered substrate specificity. Replacement of Thr119 with Ala led to a 90% decrease of activity without markedly affecting substrate binding. The mutant enzyme S122A showed normal catalytic function but impaired stability in urea solutions. These data indicate that the hydroxyl group of Thr12 is directly involved in catalysis, probably by favorably interacting with a transition state or intermediate. By contrast, Thr119 and Ser122, both putative target sites of the inactivator DONV, are functionally less important. PMID- 1287660 TI - Construction and characterization of a single polypeptide chain containing two enzymatically active dihydrofolate reductase domains. AB - A single polypeptide chain containing two dihydrofolate reductase (DHFR) sequences from Escherichia coli was constructed to determine if a repeat sequence fusion protein could be expressed in an active form. The possibility that intersequence interactions could play a significant role for this enzyme is suggested by the results of Hall and Frieden (1989, Proc. Natl Acad. Sci. USA, 86, 3060-3064) who observed a substantial decrease in the yield of active enzyme when folded in the presence of a large C-terminal fragment. The fusion protein [DHFR(Cys152Glu)--Ile--DHFR (Met1Gln)] was efficiently expressed in E. coli cells and has an activity which is twice that of the wild-type enzyme in the standard assay. The Michaelis constants of the fusion protein for the substrate, dihydrofolate and the cofactor, NADPH, are essentially unchanged from those of the wild-type protein. The urea-induced in vitro unfolding reaction of the fusion protein at low concentrations was found to be fully reversible and follow a three state model, suggesting that the two domains unfold independently. At higher protein concentrations the unfolding transition broadened and shifted to a higher urea concentration. Size-exclusion chromatography results are consistent with the formation of aggregates at the higher protein concentration, even in the absence of denaturant. PMID- 1287661 TI - Development of an optimized refolding process for recombinant Ala-Glu-IGF-1. AB - Denatured and reduced N-terminal extended insulin-like growth factor-1 (AE-IGF-1) was purified from Escherichia coli extracts and subjected to in vitro folding. The renaturation process was shown to be a function of the redox potential of the solution. Folding by different methods had no significant effect on the renaturation. A maximal yield of 60% (w/w) was obtained. The folded AE-IGF-1 was enzymatically converted to IGF-1. The major by-product (20% w/w) was identified as scrambled IGF-1. Enzymatic digestion at alkaline and acidic pH suggested two possible disulphide bond arrangements; (i) Cys6-Cys47, Cys18-Cys61, Cys48-Cys52; or (ii) Cys6-Cys52, Cys18-Cys61, Cys47 and Cys48 being in their reduced forms. Energy minimization and molecular modelling suggested that the scrambled IGF-1, having reduced cysteines at positions 47 and 48, was the energetically most stable conformation of the two. PMID- 1287662 TI - Oxygen binding and other physical properties of human hemoglobin made in yeast. AB - Wagenbach et al. (1991, BioTechnology, 9, 57-61) have recently developed a system for producing soluble recombinant tetrameric hemoglobin in yeast: hemoglobin begins to appear 4-5 h after induction with galactose, alpha- and beta-globin chains fold in vivo and endogeneously produced heme is incorporated into hemoglobin tetramers. We have further characterized the oxygen-binding properties, as well as the tetramer stability, of recombinant human Hb A made in yeast. After purification by ion-exchange chromatography, a single band at the same position as normal human Hb A was obtained using cellulose acetate electrophoresis. Although the oxy and deoxy forms of purified recombinant Hb A made in yeast were spectrophotometrically identical to native human Hb A, the oxygen-binding curve was shifted slightly left of that for native human Hb A. Further purification of recombinant hemoglobin by FPLC revealed two fractions: one (fraction B) with low cooperativity and high oxygen affinity, and the other (fraction A) with almost identical cooperativity and oxygen affinity compared with native human Hb A. The Bohr effect of fraction A was also identical to native human Hb A. Hemoglobin in fraction B with lowered cooperativity precipitated approximately 1.5 times faster than normal human Hb A during mechanical agitation, while hemoglobin in fraction A with normal cooperativity precipitated with kinetics identical to native human Hb A. These results suggest that some of the recombinant molecules made in yeast fold improperly, and that these molecules may exhibit decreased cooperativity for oxygen binding and decreased stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287664 TI - Computer-aided gene design. AB - A computer program, which runs on MS-DOS personal computers, is described that assists in the design of synthetic genes coding for proteins. The goal of the program is the design of a gene which (i) contains as many unique restriction sites as possible and (ii) uses a specific codon usage. The gene designed according to the criteria above is (i) suitable for 'modular mutagenesis' experiments and (ii) optimized for expression. The program 'reverse-translates' protein sequences into degenerated DNA sequences, generates a map of potential restriction sites and locates sequence positions where unique restriction sites can be accommodated. The nucleic acid sequence is then 'refined' according to a specific codon usage to remove any degeneration. Unique restriction sites, if potentially present, can be 'forced' into the degenerated nucleic acid sequence by using 'priority codes' assigned to different restriction sequences. PMID- 1287663 TI - Expression of the phosphorylase kinase gamma subunit catalytic domain in Escherichia coli. AB - The catalytic subunit of phosphorylase b kinase (gamma) and an engineered truncated form (gamma-trc, residues 1-297) have been expressed in Escherichia coli. The truncated protein included the entire catalytic domain as defined by sequence alignment with other protein kinases but lacked the putative calmodulin binding domain. Full-length protein was produced in insoluble aggregates. Some activity was regenerated by solubilization in urea and dilution into renaturating buffer but the activity was found to be associated with a smaller molecular weight component. Full-length protein could not be refolded successfully. The truncated gamma subunit was produced in the soluble fraction of the cell as well as in inclusion bodies. The insoluble protein was refolded by dilution from urea and purified to homogeneity, in a one step separation on DEAE-Sepharose to give a protein mol. wt 32,000 +/- 2000 with a high sp. act. of 5.3 mumol 32P incorporated into phosphorylase b(PPB)/min/nmol. Kinetic parameters gave Km for ATP 46 +/- 3 microM and Km for PPb 27 +/- 1 microM. The sp. act. and the Km values are comparable to those observed for the activated holoenzyme and indicate that the gamma-trc retains the substrate recognition and catalytic properties. The ratio of activities at pH 6.8/8.2 was 0.84. gamma-trc was inhibited by ADP with a Ki of 52 microM and was sensitive to activation by Mg2+ and inhibition by Mn2+, properties that are characteristic of the holoenzyme and the isolated gamma subunit. Calmodulin which confers calcium sensitivity on the isolated gamma subunit had no effect on the enzymic properties of gamma-trc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287665 TI - Recursive PCR: a novel technique for total gene synthesis. PMID- 1287666 TI - Dietary lipids and coronary heart disease: old evidence, new perspective. PMID- 1287667 TI - Metabolic regulations and biological functions of phospholipids in Escherichia coli. AB - Extensive genetic and biochemical studies in the last two decades have elucidated almost completely the framework of synthesis and turnover of quantitatively major phospholipids in E. coli. The knowledge thus accumulated has allowed to formulate a novel working model that assumes sophisticated regulatory mechanisms in E. coli to achieve the optimal phospholipid composition and content in the membranes. E. coli also appears to possess the ability to adapt phospholipid synthesis to various cellular conditions. Understanding of the functional aspects of E. coli phospholipids is now advancing significantly and it will soon be able to explain many of the hitherto unclear cell's activities on the molecular basis. Phosphatidylglycerol is believed to play the central role both in metabolism and functions of phospholipids in E. coli. The results obtained with E. coli should undoubtedly be helpful in the study of more complicated phospholipid metabolism and functions in higher organisms. PMID- 1287668 TI - Spectroscopy of lipid-protein interactions: structural aspects of two different forms of the coat protein of bacteriophage M13 incorporated in model membranes. PMID- 1287669 TI - The effects of water deficit stress on plant membrane lipids. PMID- 1287670 TI - [Ginkgo biloba--analysis and dosage forms]. PMID- 1287671 TI - [The clinical application of Ginkgo biloba in dementia syndromes (restoration of brain performance in vascular or degenerative CNS disease)]. PMID- 1287672 TI - [Scheele research and acclaim in travels to other countries. The 250th birthday of Carl Wilhelm Scheele]. PMID- 1287673 TI - Cytotoxic and cytostatic effects of antitumor agents induced at the plasma membrane level. AB - A variety of antitumor agents inhibit cell proliferation by interacting with the plasma membrane. They act as growth factor antagonists, growth factor receptor blockers, interfere with mitogenic signal transduction or exert direct cytotoxic effects. The P-glycoprotein encoded by the MDR1 gene represents a transmembrane protein which catalyzes the efflux of various antitumor agents. This membrane protein is the target of compounds acting as Multi-Drug Resistance (MDR) modulators. Finally, several established antitumor agents which are considered to represent DNA-targeted drugs, including anthracyclines, platinum complexes and alkylating agents, cause a variety of membrane lesions. Their contribution to the antitumor activity of these drugs is discussed. PMID- 1287674 TI - Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B. AB - This paper summarizes published data on the interactions of tubulin with antimitotic compounds that inhibit the binding of vinca alkaloids to the protein. These are all relatively complex natural products isolated from higher plants, fungi and marine invertebrate animals. These agents are maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B and their congeners. Effects on tubulin polymerization, ligand binding interactions and structure activity relationships are emphasized. PMID- 1287675 TI - Dose-response relationships with antihypertensive drugs. AB - A variety of antihypertensive drugs have been introduced into clinical practice at excessively high dose. Examples include most thiazide diuretics, propranolol, oxprenolol, atenolol, methyldopa, hydralazine and captopril. These very high doses have usually resulted from studies in which doses have been increased at regular intervals until the desired antihypertensive effect has been achieved or until unacceptable adverse effects have resulted. Frequently the starting doses were too high and the intervals between dose adjustment too short. In many cases these large doses resulted in unnecessary adverse effects--the adverse biochemical effects of thiazide diuretics, nephrotic syndrome, taste disturbances and neutropenia with captopril, the lupus syndrome with hydralazine and the central nervous system effects of methyldopa. Parallel group design with single doses and sufficient statistical power to distinguish between the upper and lower ends of the antihypertensive dose-response relationship should replace the dose escalating design. PMID- 1287676 TI - Reporting the size of effects in research studies to facilitate assessment of practical or clinical significance. AB - "Statistically significant" results may lack practical or clinical significance, and the description of results in reports of research studies is frequently incomplete or misleading in presentation of data necessary to assess such significance (effect sizes). Various common presentations are discussed, and one method of presentation of results is proposed that not only encompasses all the others, but enhances the scope of useful information conveyed in a research report. The results of the Infant Health and Development Program (IHDP) are used to illustrate the method. PMID- 1287677 TI - Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome. AB - We present our hypothesis that various steroid hormones play an important role in the symptom expression of Gilles de la Tourette's syndrome (TS) and that androgenic hormones, in particular, are likely to exacerbate symptoms of the disorder. We review the clinical evidence supporting our hypothesis. Sex steroids establish brain sexual dimorphisms early in CNS development, and we suggest mechanisms whereby androgenic and other hormonal changes later in human development might act at dimorphic brain regions to influence the natural history of TS. Finally, we discuss the various ways in which neuroendocrine studies might assist in genetic and neurobiologic research programs in TS. PMID- 1287678 TI - A critical review of menstrual synchrony research. AB - Two experiments and three studies reported a significant level of menstrual synchrony after subjects had been treated with applications of axillary extract from a donor subject or after subjects have spent time together. Four studies failed to replicate these results. A comparison of the studies shows the only consistent difference is that those studies not finding menstrual synchrony reported problems with subjects who had irregular cycle lengths, while those finding menstrual synchrony reported no such problems. All experiments and studies were based on the methods and research design introduced by McClintock (1971). Three errors are inherent in research based on her model: (1) an implicit assumption that differences between menses onsets of randomly paired subjects vary randomly over consecutive onsets, (2) an incorrect procedure for determining the initial onset absolute difference between subjects, and (3) exclusion of subjects or some onsets of subjects who do not have the number of onsets specified by the research design. All of these errors increase the probability of finding menstrual synchrony in a sample. One or more of these errors occurred in the experiments and studies reporting synchrony; no significant levels of menstrual synchrony occur when these errors are corrected. Menstrual synchrony is not demonstrated in any of the experiments or studies. PMID- 1287679 TI - Clinical relevance of antibodies against serotonin and gangliosides in patients with primary fibromyalgia syndrome. AB - The fibromyalgia syndrome (FMS) is a non-articular rheumatic disorder associated with disturbances in serotonin metabolism. In order to evaluate whether patients with FMS suffer from an autoimmune disorder, we tested sera from 50 clinically well-defined FMS patients for non-organ-specific and organ-specific antibodies by enzyme-linked immunosorbent assay and immunofluorescence test. Common antibodies against nuclei, mitochondria, and microsomes were not increased in these patients compared to healthy controls. However, 74% had antibodies against serotonin and gangliosides. The clinical and diagnostic relevance of these antibodies is supported by the absence of anti-serotonin antibodies in other rheumatic disorders such as rheumatoid arthritis, polymyalgia rheumatica, and collagen diseases. These antibodies may belong to the group of antireceptor antibodies, considering the fact that gangliosides are an important component of the serotonin receptor. It remains to be determined whether these antibodies are of pathogenetic relevance, interfering with serotonin binding and thereby inducing symptoms associated with FMS. PMID- 1287680 TI - Pituitary-gonadal function during sleep in healthy aging men. AB - There is limited information on the relation between age-related changes in pituitary-gonadal function and sleep physiology in older men. In this cross sectional study of 67 healthy volunteers free from sleep complaints, aged 45-75 yr, we (1) assessed peak fluctuations and hourly variations in plasma testosterone, LH and prolactin sampled every 20 min during sleep, and (2) explored the relation between sleep parameters, respiratory and periodic leg movement disturbances, and circulating concentrations of the aforementioned hormones. We hypothesized that alterations in sleep architecture or presence of sleep disorders may contribute to hormonal variations in aging subjects. Bioavailable testosterone decreased and LH increased with age, but there were no differences in total testosterone and prolactin and no major changes in peak hormonal release. There were positive associations, independent from the age effect, between sleep efficiency, decreased latency to onset of REM activity, and number of REM episodes, and circulating testosterone. Sleep-disordered breathing significantly increased with age. The degree of respiratory disturbance was associated with decreased overnight plasma bioavailable testosterone, but this relationship lost its significance after age-adjustment. The findings demonstrate a decrease in gonadal function during sleep in healthy aging men and suggest that changes in sleep efficiency and architecture are associated with alterations in gonadal activity in these older individuals. PMID- 1287681 TI - Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics. AB - Apomorphine challenge tests (0.5 mg SC) were performed in 14 normal male volunteers and in 9 male schizophrenic inpatients, drug-free for at least 2 wk. In the normal volunteers, apomorphine induced an increase of serum growth hormone (GH) (maximum at 40 min), of vasopressin-neurophysin (hNpI) (maximum at 20 min), and oxytocin-neurophysin (hNpII) (maximum at 20 min). The release of neurophysins was independent of digestive side effects. In the schizophrenics, the GH level and release pattern were similar to those in the controls. The basal level of hNpI was reduced (t0: 0.42 +/- 0.1 ng/ml in the schizophrenics and 0.66 +/- 0.05 ng/ml in the controls, p < 0.02). In contrast, the basal level of hNpII was increased (3.34 +/- 0.04 ng/ml in the schizophrenics to 0.92 +/- 0.21 ng/ml in the controls, p = 0.001). The response to apomorphine was blunted, with no significant release of hNpI or of hNpII. Although the hNpII data are consistent with an increased dopaminergic tone, the psychopathological meaning of the increased basal oxytocinergic and decreased vasopressinergic functions remains to be defined. PMID- 1287682 TI - The effects of menstrual phase and nicotine abstinence on nicotine intake and on biochemical and subjective measures in women smokers: a preliminary report. AB - Nicotine intake, menstrual and smoking withdrawal symptomatology, and baseline cortisol and MHPG were assessed in nine women smokers under conditions of ad lib smoking and overnight abstinence in three menstrual phases (early follicular, mid to-late follicular, and late luteal). A trend towards higher nicotine intake (p < 0.10) was observed in the mid-to-late follicular phase. Although menstrual symptomatology was not significantly elevated during the smoking abstinence condition overall, abstinence appeared to prevent the normal reduction in symptomatology during the mid-to-late follicular phase that occurred under conditions of ad lib smoking. Menstrual and withdrawal symptoms were highly correlated, and both were most pronounced during the late luteal/abstinence condition. The smoking-specific item "craving" reflected this pattern, though in attenuated form, suggesting that the observed exacerbation of withdrawal symptomatology was not simply due to generalized dysphoria, as queried in both instruments. MHPG was significantly elevated in the late luteal phase, whereas cortisol was significantly higher during ad lib smoking than during abstinence and tended to be highest in the mid-to-late follicular phase. Further investigation will be needed to determine the functional significance of these findings for understanding and treating smoking in women. PMID- 1287683 TI - Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men. AB - Further evidence that nocturnal erections are androgen-dependent and erectile responses to visual erotic stimuli are androgen-independent is presented from six men with secondary hypogonadism and six eugonadal controls. Erections during sleep were substantially less in the hypogonadal men, in terms of both tumescence and rigidity. In response to visual erotic stimuli, the percentage increase in circumference over baseline and the increase in rigidity were similar for the two groups. PMID- 1287684 TI - Coping and the ineffectiveness of coping influence the outcome of in vitro fertilization through stress responses. AB - The effect of a coping-ineffectiveness of coping construct and of psychoendocrine stress responses upon the outcome of in vitro fertilization treatment was investigated in 40 women. Women with a high Zung depression score, high active coping, high avoidance, and a high expression of emotion have lower pregnancy rates. The mechanisms for this personality effect are not clear, although the desensitization-stimulation process (FSH, E2 concentrations) seems to be involved. The psychoendocrinological responses to the stress of oocyte retrieval and embryo transfer are important: Women with high anticipatory state anxiety levels and high anticipatory cortisol concentrations have lower pregnancy rates. The influence of prolactin stress concentrations is unclear: Women with high prolactin concentrations seem to have more oocytes but lower fertilization rates. PMID- 1287685 TI - Psychosocial aspects of hyperprolactinemia. AB - Fourteen mildly hyperprolactinemic women and 14 matched controls were compared with respect to biographical data, self-reported emotional and somatic well being, and cortisol production. The patients had significantly more often experienced a separation from their parents in childhood. No differences were found for cortisol levels and emotional and somatic well-being. Future studies also should focus on personality, coping, and defense mechanisms in order to explain these contrasting findings. PMID- 1287686 TI - Changes in burying behavior during the estrous cycle: effect of estrogen and progesterone. AB - This study demonstrates changes in cumulative burying behavior during various phases of the rat estrous cycle. Low levels of burying behavior were observed during late proestrus. Similar burying behavior levels among females tested in early proestrus, metestrus or diestrus and ovariectomized females were found. In ovariectomized females, treatment with estrogen (E) produced a slight, non significant reduction in burying behavior. In contrast, progesterone (P) treatment resulted in a dose-dependent, statistically significant decrease in time spent burying. The combined treatment of E and P produced no effect. These data are discussed from the standpoint of the putative anxiolytic effect of P. PMID- 1287687 TI - Effects of chronic corticosterone treatment on electrophysiological and behavioral measures in the rat. AB - The electrophysiological and behavioral effects of daily oral exposure to a corticosterone or vehicle solution was evaluated in 20 male Wistar rats over a 10 wk period. Evaluation of the rats' behavior in an open field apparatus, as well as in automated locomotor cages, revealed no significant differences between steroid-treated and control animals following 5-6 wk of exposure. No differences in mean EEG power, as estimated by spectral analysis of cortical and dorsal hippocampal recordings, were observed between the two groups following 8 wk of exposure. However, some increases in EEG "stability" were noted in the corticosterone-treated rats. At 9 wk, responses to auditory stimuli, as assessed by evoked responses, in cortex and dorsal hippocampus were also found to be unaltered by corticosterone exposure. These studies suggest that exposure to daily oral corticosterone, in the doses used, over a period of 2-3 mo is not associated with gross electrophysiological or spontaneous behavioral effects in the brain areas assessed. PMID- 1287688 TI - Cortisol concentrations and the social significance of rank instability among wild baboons. AB - Previous work has shown that dominant primates in stable social hierarchies in a number of species often have low basal cortisol concentrations, relative to subordinate individuals. In contrast, this trait appears to be lost during periods of social instability, probably reflecting the psychological stressfulness of the instability. The present study examined whether basal cortisol concentrations were elevated not only when the overall hierarchy was unstable, but also were elevated in individuals which, within a stable hierarchy, were nevertheless in the process of their own rank shifting. Study subjects were a population of male olive baboons living freely in a national reserve in East Africa, which could be anesthetized under conditions allowing for determination of basal cortisol concentrations. The instability of a particular rank was quantified by determining the percentage of dominance interactions that represented a reversal of the already established direction of dominance. Highly unstable relationships with the rest of the males in the hierarchy did not predict elevated basal cortisol concentrations in an individual. Instead, it was the stability of interactions with males close in rank (within three steps in the hierarchy of the individual) which predicted cortisol concentrations: the greater the percentage of interactions that were reversals with the three nearest lower ranking males, the higher the basal cortisol concentrations in an individual. In general, high rates of such reversal interactions indicated that the male was being challenged for his more dominant position.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287689 TI - Intracerebroventricular LHRH may serve as a discriminative stimulus in male rats. AB - Male Wistar rats (N = 16) were trained to discriminate 5 micrograms/kg LHRH, injected intraperitoneally, from saline in a two-lever, food-reinforced drug discrimination procedure, with an injection-session interval of 45 min. Reliable discrimination of LHRH was acquired within 60 training sessions. Subsequent generalization tests in brain-cannulated animals showed dose-dependent and time related partial substitution of intracerebroventricular LHRH for intraperitoneal LHRH (ventricle doses ranged from 25-400 ng, and the injection-session intervals ranged from 10-40 min). These results indicate that centrally administered LHRH may serve as a dose- and time-dependent discriminative stimulus in male rats. PMID- 1287690 TI - [Psychology of male and female desire for children. Developmental conditions of narcissistic, depressive and creative aspects]. AB - Conscious and unconscious determinants of the wish for a child deriving from early childhood are demonstrated. In this context the elaboration of phase specific narcissistic mortifications in connection with the recognition or repression of ambivalence is given prime importance. The acceptance of the ambivalence and triangulation have the effect that the creative aspects in the later wish for a child are more powerful than the narcissistic or depressive parts. PMID- 1287691 TI - [Pregnancy, labor and partnership relations in a family with a "retort baby". Follow-up of "IVF couples" and their children]. AB - Nowadays, in vitro fertilisation can be judged as a relatively successful treatment in special cases of sterility. Success cannot be defined only by induction of pregnancy, but must also be taken into consideration the couple's and the "IVF-children's" personal situation. The main problem of IVF is the high multiple rate of nearly 20%, resulting in a higher frequency of preterm deliveries. This leads to higher perinatal mortality and more longterm deficiencies in these children. The women's attitude during pregnancy can be considered to be responsible. From a psychosomatic point of view (the husband's presence during delivery, breast feeding etc.) there are favourable preconditions for the "birth of the family." In most cases, the couples give a contented or good view of their partnership (self-assessment). Nearly 5% of them seem to be "disappointed" after the birth of the baby. The method of IVF is positively assessed from an overall point of view. But only half of the women do not keep this special method of procreation secret. PMID- 1287692 TI - [Sterility--a woman's concern? Coping behavior and partnership structure of sterile couples of various diagnostic groups]. AB - Three groups of sterile couples with functional, tubal and andrologically caused sterility were compared for the evaluation of sex- and diagnosis-dependent kinds of overcoming of their disease. Anamnestic data, anxiety, the coping strategy of sterility and as well the couple and personality structure are analysed. Independent of the organic cause of sterility the women showed a higher emotional reaction level (anxiety, coping stress) than their husbands. In all groups the "healthy" partners dominate. The subfertile men seem to be more subordinate, less engaged and interested and not so anxious as their wives and as the husbands of tubal sterile women. The healthy women with andrologically caused sterility present a highly emotional engagement in the overcoming and treatment of their disease. Possible emotional mechanisms and social stereotypes of self presentation are discussed, which may cause the intense engagement of the women independent of the organic cause of sterility. PMID- 1287693 TI - [A study of the psychosomatic aspects of endometriosis]. AB - Based upon existing psychological studies of endometriosis, the hypothesis was tested if patients suffering from this disorder differ from other infertile females with respect to psychological characteristics. Using questionnaires as well as a semi-structured psychotherapeutic interview 38 patients with endometriosis and 18 females with tubal sterility were investigated. A comparison of both groups indicated a higher level of anxiety and some evidence for a somatic preoccupation in the endometriotic patients. The analysis of the interviews (which were judged by several independent raters) confirmed the hypothesis of gender role conflicts in combination with endometriosis. This conflict seemed to be characterized by a negative experience of menarche and puberty, early gynecological problems and negative sexual experiences. This constellation is illustrated using a typical case. Based upon these results, further studies of endometriosis using a psychosomatic perspective seem to be promising. PMID- 1287694 TI - [Self concept and body image in involuntary sterility]. AB - From theoretical reasons and clinical experience with infertile women, an impairment of the self-image and the body-image was to be expected with involuntarily childless people. Our hypothesis was tested in a sample of 107 subjects. 59 of them (f = 30, m = 29) were patients undergoing treatment for infertility. The two control groups consisted of 24 parents and 24 (voluntary) nonparents. Four instruments were used: 1. a modified version of the Role Construct Repertory Test according to Kelly (1955); 2. rating scales concerning different parental and non-parental roles; 3. the Questionnaire About One's Own Body by Strauss and Appelt (1983); 4. our Questionnaire About Problems Caused by Involuntary Childlessness. Contrary to what we expected, we neither found greater distances between self and ideal self nor an unfavourable body-image in involuntarily childless subjects. The male patients presented themselves even more self-confident and more attractive than the men of the control groups. PMID- 1287695 TI - [Psychological factors of non-ulcer dyspepsia]. AB - Given the absence of any demonstrable organic reason for non-ulcer dyspepsia, and the well known fact, that the psyche influences stomach function, it is widely held, that psychological factors cause NUD. To now, studies are concerned with the psychopathology and personality of NUD-patients, their illness behaviour, and with the relation between stress and abdominal pain. A critical review of these studies revealed, that among the psychological variables mainly anxiety and illness behaviour seems to play a central role in NUD. However, future studies should focus more on the distinction towards other functional disorders and on the differentiation within the heterogeneous group of NUD-patients (especially with regard to physiological variables). Besides this, it seems rewarding to examine the so far scientifically neglected group of subjects with abdominal pain, who do not contact a physician. PMID- 1287697 TI - [Reminiscence therapy with the elderly]. AB - Extending the possibilities of psychotherapeutic treatment, reminiscence therapy and life review seem to be especially suited to help elderly patients cope with crisis or depression. However, there are still many differences in methods and techniques applied. In this article, the role of the past in depression, previous research on reminiscence therapy as well as its possible goals and methods are considered. An example of reminiscence group therapy in a psychogeriatric day hospital is presented. PMID- 1287696 TI - [Characteristics and problems of Balint groups with medical students]. AB - For a period of seven years medical students have had the opportunity to attend Balint-seminars in an intensive training course in the field of "Medical Psychology and Psychotherapy" during their clinical education. In groups of 10-15 students the participants study conscious and subconscious aspects in the relationship between students and patients in the setting of their practical work in hospital. Some of these students additionally hold supporting conversations with mentally and psychosomatically ill patients. This takes place at the Psychotherapeutic Department and at the Department of Psychiatry, both at Innsbruck University, and is supervised in the Balint-seminars. In addition to this psychoanalytically oriented supervision theoretic knowledge (socio-psycho somatic aspects of illnesses, subconscious aspects in the doctor-patient relationship, phenomena of transference and counter-transference) is being brought across. In the students' Balint-seminars both patient-related self experience and the reflection upon the students' social role in hospital acquire special importance. The development of this model of teaching and learning and the experiences which have been achieved over the last seven years are described in this article concerning the practicability for a patient centered model in the education of medical students. PMID- 1287698 TI - [Does the endless increase in knowledge finally lead to a change in attitude? On the distinction between instruction and education in medicine]. AB - In view of the overwhelming increase in our knowledge of the sciences, a call for desirable integration is being made from the practical standpoint. A change of attitude is being recommended to help the practitioner let his daily dealing with any one patient be less determined by general obligations and more by concrete necessities, thereby creating a balance with a firm hold on reality. An appropriate education should not be understood as bare instruction in established knowledge and abilities but requires above all real, practical training which also considers how we might deal thoughtfully with the fruits of our knowledge. This way of thinking cannot itself be taught as a subject of knowledge. A differentiation between education and instruction is suggested, questioning the tendency often uncritically to "force into line", thus allowing a value determining new orientation. Psychotherapy--especially with the practical experience of relationships on which it is based--has to be aware of its specific function within the entire scope of human medicine and the importance of and dangers to this function are discussed. PMID- 1287699 TI - [Coping with illness by chronically ill adolescents and young adults--an empirical study]. AB - From June 1990 to January 1991 86 chronically ill adolescents and young adults who had come to the vocational assessment unit of the rehabilitation center or for vocational guidance to the rehabilitation hospital, both in Neckargemund/Germany, were examined with regard to their coping with their illnesses. The Freiburg questionnaire for coping with illness was applied, and the Trait-instruction was given because persons with inborn disabilities were part of the sample. Also, the type of illness or disability and motorial handicap as well as the non-verbal intelligence were included. The results of three different medical diagnosis groups don't show any differences in the coping with illness. Persons with motorial handicaps are able to cope with their disabilities as well as persons without motorial handicaps. Adolescents and young adults with inborn or early acquired illness/handicap show a greater loss of confidence in the medical doctors than persons who were taken ill at the age of 6 or later. PMID- 1287700 TI - ["... and found no shade". Coping processes of patients with erythropoietic protoporphyria]. AB - Coping with disease was studied in a group of ten persons suffering from erythropoietic protoporphyria (EPP), a chronic congenital metabolic disorder that manifests itself in extreme sensitivity to ultraviolet light. Sufferers experienced medical prophylaxis as ineffective or counterproductive. The BEFO technique (Berner Bewaltigungsformen BEFO, 3 dimensions, 27 categories) was used in assessing the coping strategies. The sufferers' interviews were evaluated on the basis of transcripts. Stressors and respective coping strategies were defined and analysed for each person individually. Sufferers are confronted with their disease virtually every day. For each stressor the set of strategies tends to be specific either to the disease, the environment or it may reflect personality traits. Most of the sufferers did not develop an effective mode of adaptive behavior, i.e. coping with the pain/stigma dilemma, until they passed their third decade. While it undeniably presents an intense personal challenge, coping with disease must be seen to include major societal aspects as well. PMID- 1287701 TI - [Attitude to death and control behavior of medical students--a cross sectional study]. AB - Within the scope of a cross-section study the Fear of Death Questionnaire (Hensle 1977), the Semantic Differential of the term Death (Potthoff 1980) and the IPC questionnaire (Krampen 1981) were submitted to n = 186 first- and second-year medical students and to n = 151 third- and fourth-year medical students. This was to trace the question how far the attitude toward death and the locus of control of medical students vary in the course of their education. In comparison with most of other respective publications our paper did not show any significant changes of their attitude toward death and their locuis of control neither. After more detailed analysis of the data discerning consideration of the fear of death questionnaire mentioned above is to be demanded prior to further use in medical fields. At least in view of medical students it's value regarding the construct validity is to be questioned. Concerning the Semantic Differential at least one adjective pair should be eliminated in future. PMID- 1287702 TI - [The complexity problem and reductionist solutions--critical comments from the psychoanalytic viewpoint]. AB - We refer to the essentials of the complexity of psychosomatic and psychoneurotic phenomena and how to comprehend this complexity. Measurement is called in question as a possibility to describe psychic phenomena. We make a suggestion to preserve the advantages and to overcome the disadvantages (selective awareness, no generalization, no intersubjective validitation) of clinical psychoanalytic research work. PMID- 1287703 TI - [Concepts of anthroposophic psychiatry and their contribution to understanding schizophrenia]. AB - A concept of central importance in alternative forms of psychiatry, namely the concept of the etheric body, is elaborated in reference to disturbed body sensations of schizophrenic patients. In the non-orthodox approach the etheric body, i.e. a spatial organisation of forces active in the organism that is perceived only under specific circumstances, is a mediating medium between body and soul. The concept of the etheric body proves to be associated with both, the still unsolved body-mind-problem and the problem of conceptualising psychic energy. Schizophrenia is interpreted as a disorder in which the connections between body, etheric body and mind have come loose. PMID- 1287704 TI - Tuberculosis in patients infected with human immunodeficiency virus 1. A retrospective multicentre study of 123 cases in France. The Groupe des Infectiologues du Sud de la France. AB - In order to study the epidemiological, clinical, and progressive characteristics of TB in HIV-infected individuals, a retrospective study was conducted in nine infectious disease centres of university hospitals located in the southern half of France. Among the 5730 HIV-seropositive in- and out-patients, 123 (2.1 per cent) had TB (121 infections caused by M. tuberculosis, 2 by M. bovis). Tuberculosis was pulmonary in 53 patients (43.1 per cent), extrapulmonary in 36 patients (29.3 per cent), and combined in 34 patients (27.6 per cent). There was no statistically significant difference among these three locations as to the mean CD4 count/mm3 (160 +/- 17), the type of antituberculosis therapy, the length of treatment (10.8 +/- 0.6 months) and the outcome. Fifty-two (45.2 per cent) patients received an initial antituberculosis therapeutic regimen of four drugs: isoniazid, rifampicin, ethambutol, pyrazinamide; 54 (46.9 per cent) were started on three drugs: isoniazid, rifampicin, ethambutol; and nine (7.8 per cent) received a two-drug combination: isoniazid, rifampicin. Fourteen of 75 patients subsequently received secondary preventive therapy. The mean follow-up time was 252 +/- 290 days. Clinical healing was obtained in 57.7 per cent of patients. Forty-six patients died, 33 during treatment: 23 from AIDS and eight from TB (in the first 3 weeks of treatment). Five patients suffered from relapses due to poor treatment compliance. Patients had a good prognosis if tuberculosis was diagnosed early. PMID- 1287705 TI - Renal disease associated with circulating antineutrophil cytoplasm activity. AB - We report our detailed observations on a group of 30 consecutive patients with renal disease, histologically demonstrated glomerulitis or necrotizing vasculitis, and circulating antineutrophil cytoplasm activity (ANCA). The annual incidence of ANCA-related renal disease was seven cases per million population. The sensitivity of serum ANCA for histologically proved glomerular vasculitis was 79 per cent, with a specificity of 87 per cent. Most patients responded to treatment with cyclophosphamide and steroids but complications of therapy occurred in just over half the patients and were serious in 20 per cent. Actuarial survival at 1 year was 60 per cent. Age and dialysis requirement did not influence outcome and the only identified adverse prognostic factor was hypoxic lung disease. We conclude that the association of ANCA with renal disease is not rare and that positive serology accurately identifies a homogeneous group of patients with similar clinical, histological, and prognostic features. Separation of these patients into those with the disease entities of Wegener's granulomatosis and microscopic polyarteritis is not straightforward on clinical and histological criteria, and such a distinction does not yield useful therapeutic or prognostic information. Simple urinalysis should always be carried out in patients with undiagnosed systemic illness in order to identify renal disease. ANCA-related renal disease can be treated successfully with cyclophosphamide and steroids and elderly patients should not be excluded from treatment, including dialysis if necessary. The ANCA test is simple and quick to perform and, in the appropriate clinical setting, accurately identifies patients who may benefit from immunosuppressive treatment before a histological diagnosis can be established. PMID- 1287706 TI - Plasma exchange treatment and prognosis of Guillain-Barre syndrome. AB - A retrospective analysis of case notes was undertaken for 52 patients presenting to Guy's Hospital with Guillain-Barre syndrome between August 1987 and September 1990. Twelve months after onset 61 per cent of patients had recovered completely, 35 per cent were still significantly disabled and two patients (4 per cent) had died. Forty-eight of the patients (92 per cent) were treated with plasma exchange. The frequency of morbidity related to this treatment was low, and plasma exchange was not responsible for either of the deaths. Outcome for all patients treated with plasma exchange between January 1985 and September 1990 was compared with that of 64 patients with Guillain-Barre syndrome seen in 1983 and 1984 who were not treated in this way. Time to walking unaided was significantly better (median 58 days compared with 86 days, p = 0.031), as was the median duration of ventilation (16.5 compared with 36 days, p = 0.004). Factors which had been found to predict an adverse outcome in previous studies (requirement for ventilation, age over 40 years, time to becoming bedbound less than 4 days, and small distally evoked abductor pollicis brevis muscle action potential) were not significantly associated with a poor prognosis in this study. The features associated with persisting disability were time to improvement more than 21 days, preceding diarrhoea and older age. PMID- 1287707 TI - Frequency analysis of ventricular fibrillation and resuscitation success. AB - In 56 patients, frequency analysis of the electrocardiogram of ventricular fibrillation exhibited power spectra with a distinct dominant frequency. The greatest success for resuscitation from ventricular fibrillation is recorded when ventricular fibrillation develops after the patient comes under coronary care. Of the 41 patients in whom the onset and first 8 s of ventricular fibrillation were artefact-free the mean dominant frequency of primary ventricular fibrillation (no cardiogenic shock or cardiac failure) in 21 patients was 6.2 +/- 0.2 Hz, significantly higher than the mean dominant frequency of the first 8 s of secondary ventricular fibrillation (cardiogenic shock or heart failure) (4.0 +/- 0.2 Hz, 20 patients, p = 0.0001). In these patients the peak-to-trough amplitude (ECG) of the first 8 s of ventricular fibrillation was similar in both primary and secondary ventricular fibrillation as was the mean duration of ventricular fibrillation prior to the first DC shock. There was a significantly lower success rate for resuscitation from secondary ventricular fibrillation (6 of 20 patients) compared with resuscitation from primary ventricular fibrillation (18 of 21 patients, chi 2 17.8, p = 0.001). Of the remaining 15 patients who were collapsed between 3 and 20 min before the arrival of the mobile coronary care unit, the dominant frequency of the first 8 s of ventricular fibrillation fell with increased duration of collapse (from 5.5 Hz at 3 min to a mean of 2.1 Hz at 20 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287708 TI - The Association of Physicians of Great Britain and Ireland 1992. PMID- 1287709 TI - Single-tooth home bleaching. AB - This article describes a simple but effective method of bleaching single vital discolored teeth. The patient applies a viscous 10% carbamide peroxide gel in a plastic mouth-guard designed to confine the gel only to the discolored tooth. This method has been effective for lightening vital teeth with calcified pulpal spaces. PMID- 1287710 TI - Clinical significance of holes in gloves for dental use: a spectrophotometric analysis. AB - The aim of this study on latex dental gloves was to establish whether there is any relationship between faults that are detected by filling with water and the entry of liquid into the gloves during use. Twenty-four gloves of different sizes were examined. Large and small holes randomly distributed on the index, middle, and ring fingers, were made in the gloves. The gloves were filled with water and squeezed to detect the amount of water escaping. A mass spectrophotometer was used with the same gloves to quantify the entry of an aqueous solution of potassium bichromate during work. The filling method was effective for revealing all faults in gloves, but it was not able to determine whether there would be fluid entry through the holes during work. While the size of the holes was not predictive for the amount of liquid entering the glove, adherence of the glove to the hand was. Holes of the same size allowed a greater entry of contaminated liquid in adherent gloves than in looser ones. PMID- 1287711 TI - The importance of proximal curing in posterior composite resin restorations. AB - This in vitro study compared the marginal adaptation of enamel-bonded mesio occlusodistal composite resin restorations placed using two different insertion techniques (one-step and two-step) and three different curing techniques (occlusal using opaque matrix and wedge systems and interproximal using transparent matrix systems and either transparent, non reflecting, or transparent, laterally reflecting wedges). The micromorphology of the enamel restoration interface and the marginal seal were evaluated after the restorations were exposed to mechanical and thermal stresses. Although the difference was not statistically significant, the marginal quality of the restorations placed with the two-step technique was better than that of the restorations placed with the one-step technique. The restorations cured from the interproximal direction had significantly better marginal adaptation than did restorations cured only from the occlusal direction. The quality among the groups of interproximally cured restorations was not significantly different, because all the restorative techniques that were evaluated resulted in generally poor marginal quality. PMID- 1287712 TI - Identification of dental implants on radiographs. AB - In the future, dentists will more frequently encounter patients who have dental implants. To use radiographs to identify implants that were previously inserted by other dentists, dentists have to be familiar with the detailed morphology of different products and types of fixtures as well as with the principles for formation of their radiographic images. In the present study, radiographic images of ten common dental implants were analyzed. Images varied with viewing angles. The influences of surface structures, such as threads, cuts, holes, perforations, and flutes, are demonstrated. PMID- 1287713 TI - The effect of zinc chloride dentifrices on plaque growth and oral zinc levels. AB - The antiplaque potential of zinc salts has been previously demonstrated. The purpose of the present investigation was to establish the effect of zinc chloride dentifrices on plaque growth and on the concentration of zinc in saliva and plaque. Zinc levels in saliva and plaque were measured by atomic absorption spectrophotometry. Elevated zinc levels were observed in saliva and in plaque for 1 hour after contact with a zinc chloride dentifrice. Increased concentrations of zinc were also observed in plaque residue. Further analysis of data showed that subjects with high rates of plaque growth benefited more from the zinc dentifrices than did those with low rates of plaque growth. PMID- 1287714 TI - Resin bonding to wet substrate. II. Bonding to enamel. AB - In part I of this study, it was reported that high shear bond strengths to dentin were obtained by using a particular dentin-enamel bonding system on wet dentin. Because it would be difficult to dry the enamel without drying the dentin, an investigation was undertaken to determine if the treatment of enamel surfaces with various phosphoric acid concentrations would be successful on wet enamel using the same bonding system. It was discovered that the bond strengths to etched and wet enamel using a particular dentin-enamel bonding system were equal to or higher than bond strengths to etched and dry enamel. PMID- 1287715 TI - The effect of polymerization shrinkage during veneer placement. AB - This study evaluated the relationship of polymerization shrinkage during composite resin veneer placement to direction of the polymerization light source. Fifty maxillary permanent incisors were obtained and divided into five groups of ten. Groups I and II had preparations placed in enamel. Groups III, IV, and V had preparations placed in dentin. In groups I and III, an unfilled bonding resin was placed and polymerized from the facial aspect, followed by placement and polymerization of a hybrid composite resin. Groups II and IV were initially polymerized from the lingual direction. In group V, the unfilled resin and hybrid composite resin were polymerized simultaneously from the facial aspect. Statistical analysis indicated that there was significantly less axial microgap formation during lingual polymerization when the preparation remained in dentin, but demonstrated that there was no statistically significant difference when the preparation remained in enamel. PMID- 1287716 TI - Bond strength of glass-ionomer cement and composite resin combinations. AB - The tensile bond strength to dentin was measured for three glass-ionomer cement and composite resin combinations: two light-curing glass-ionomer cements (Vitrebond and XR-Ionomer) and one traditional glass-ionomer cement (Ketac-Bond), two adhesive systems (Scotchbond, and XR-Bonding System), and a corresponding composite resin. The bond strength of this "sandwich" was also compared with that of the same cements used in bulk. Vitrebond showed a significantly higher bond strength in bulk than did the other two cements. Of the sandwiches, the XR Ionomer and XR-Bond combination showed a bond strength significantly higher than that of the Vitrebond and Scotchbond or Ketac-Bond and Scotchbond combination. The fracture of the bond was mainly adhesive for Vitrebond, cohesive for XR Ionomer when used in bulk and adhesive-cohesive when used in a sandwich, and cohesive for Ketac-Bond. PMID- 1287717 TI - The relative shear bond strength of visible light-curing and chemically curing glass-ionomer cement to composite resin. AB - The purpose of this study was to compare the shear bond strength to composite resin of a light-curing glass-ionomer cement with that of various chemically curing glass-ionomer cements. Light-cured composite resin cylinders were bonded to cylindrical glass-ionomer substrates after etching for 30 seconds with 37% phosphoric acid. Specimens were maintained in distilled water for 7 days and then thermocycled in water baths. One group of light-cured glass-ionomer cement substrates was not etched. The interfacial bond strength of these specimens was measured in shear. Cement shear strength was also evaluated. Statistical analysis showed the light-curing cement to have a significantly higher bond strength to composite resin than any of the chemically curing cements tested. PMID- 1287718 TI - Distribution of calcium in ischemic brain of gerbils. PMID- 1287719 TI - Isolation of transcriptionally regulated sequences associated with neuronal and non-neuronal cell interactions. PMID- 1287720 TI - A century of neuronal and neuroglial interactions, and their pathological implications: an overview. PMID- 1287721 TI - Neuronal and astroglial monoamine oxidase: pharmacological implications of specific MAO-B inhibitors. PMID- 1287722 TI - Gangliosides and neuronal-astrocytic interactions. PMID- 1287723 TI - CNS glial scar tissue: a source of molecules which inhibit central neurite outgrowth. PMID- 1287724 TI - Glial modulation of neural excitability mediated by extracellular pH: a hypothesis. PMID- 1287725 TI - Role of astrocytes in aging: late passage primary mouse brain astrocytes and C-6 glial cells as models. PMID- 1287726 TI - Association between cell-mediated demyelination and astrocyte stimulation. PMID- 1287727 TI - Oligodendroglial and neuronal cytoplasmic inclusions in multisystem atrophy. PMID- 1287728 TI - Astrocytes and Parkinson's disease. PMID- 1287729 TI - The involvement of astrocytes and an acute phase response in the amyloid deposition of Alzheimer's disease. PMID- 1287730 TI - S100 beta and serotonin: a possible astrocytic-neuronal link to neuropathology of Alzheimer's disease. PMID- 1287731 TI - Astrocytic gliosis in the amygdala in Down's syndrome and Alzheimer's disease. PMID- 1287732 TI - Functional consequences of astrocytic swelling. PMID- 1287733 TI - Three-dimensional MR vascular imaging of the spine using gadolinium-DTPA. AB - To investigate the fine vascular structures in the spinal and paraspinal region, the authors performed three-dimensional GRASS scanning after the administration of contrast material. The scan sequence was sagittal volume scan, TR/TE 100/16, with a flip angle of 45 degrees. First-order gradient moment nulling was employed. Four normal volunteers and 31 patients were studied. Using this technique, longitudinal anterior epidural veins and vertebral arteries were clearly identified. Paraspinal fine vessels of slow to moderate flow, including dilated anterior spinal artery, radiculo-medullary vein, and perimedullary coronal venous plexus, were demonstrated in pathological cases. In addition, with processing of the volume data set, phlebographic projection images of the ladder shaped anterior epidural venous system could be generated. This method provided more detailed information on epidural and intradural vessels than conventional MR imaging. PMID- 1287734 TI - Correlation of CT patterns with histologic findings in parauterine masses. AB - CT findings were correlated with histologic and surgical findings in 162 parauterine masses. CT findings were classified into four types and 14 patterns. These classifications were useful in the diagnosis and differential diagnosis of parauterine masses. Malignant ovarian tumors, uterine myogenic tumors, metastatic tumors, endometrial cysts, and benign cystadenoma revealed characteristic CT findings, making differential diagnosis possible on CT. Contrast enhancement of the solid part, bilaterality, and the presence of ascites were useful for differential diagnosis. Although CT is one of the major modalities for the diagnosis of intrapelvic mass lesions, MR imaging will be another important method for the delineation and characterization of these lesions in the future. PMID- 1287736 TI - Thyroid carcinoma associated with hot nodule diagnosed by ultrasonography. AB - A patient with thyroid carcinoma showing a hot nodule on radioiodine scintigraphy was examined by ultrasonography and was revealed to have occult carcinoma co existing with adenomatous goiter. Ultrasonography should be performed to establish the diagnosis even if radioiodine scintigraphy reveals a hot nodule, as should fine-needle aspiration biopsy. PMID- 1287735 TI - Uterine leiomyoma: correlation between signal intensity on magnetic resonance imaging and pathologic characteristics. AB - To correlate the signal intensity of uterine leiomyoma with its pathologic characteristics, with particular emphasis on the fibrous component, 33 magnetic resonance (MR) examinations that revealed 93 leiomyomas were prospectively studied. All patients were imaged in axial and sagittal planes with different spin-echo pulse sequences to obtain T1-, T2-weighted, and proton density images. Nondegenerative leiomyomas (n = 62) showing a homogeneous signal of low intensity, and degenerative leiomyomas (n = 31) with a heterogeneous signal of variable intensity on T2-weighted images could be correlated. Histopathological assessment of fiber constitution and degeneration, and MR intensity were interpreted by independent observers. There was excellent accord between the averages for MR intensity, T2 relaxation time and fiber content, although the intensity values in each fiber grade showed a wide range. The greater the fiber content the lower the MR intensity on T2-weighted images, and the shorter the T2 relaxation time (p < 0.0001). In addition, the manner in which fiber distribution affected MR appearance was also elucidated. These data contribute guidelines for precise tissue differentiation of myogenic tumors on MR images, and for MR imaging tissue diagnosis of any lesion with a considerable fibrous element. PMID- 1287738 TI - [The epidemiologist facing assessment of low risk]. AB - Epidemiological studies on low risks involve a number of major methodological difficulties. This review defines the concept of low risk and emphasises the need to control all large, possibly disease-related risk factors, before low risk factors can be evaluated. This procedure is also essential in identifying confounding factors. There is a special need to evaluate statistical power in studies on low risk factors, and the representativeness of both cases and controls should be carefully verified, particularly in case-control studies. The need to control the researcher's wish bias and the main requirements for meta analysis are also presented. PMID- 1287739 TI - [Are accidents accidental? Prevention of injuries in children and adolescents]. AB - This paper reviews the preventive strategies that have been used in different regions and countries to reduce the morbidity and mortality linked with injuries in children and adolescents. It is confined to programmes and initiatives of different kinds that have been evaluated. Strategies can concentrate on the circumstances leading to an accident, or on reducing the consequences of injury. They can be passive (window gates, speed limits, drug packaging) or active (use of helmets, training of young drivers). They can be specific (focusing on falls or burns) or non-specific (promoting low-risk behaviour in young people). In each case prevention must allow for the developmental stage of the target population, and be conceived and implemented through multidisciplinary approaches. It should be developed at national as well as regional and local levels. Finally, improvements must be made to the means of evaluating prevention strategies. PMID- 1287737 TI - Confirmation of dialysate leakage by intraperitoneal administration of radioactive colloid. AB - A 29-year-old man who had been on continuous ambulatory peritoneal dialysis (CAPD) was admitted to our hospital because of pleural effusion. Radioactive colloid studies with intraperitoneal administration revealed a pleuroperitoneal communication. After pleurodesis by the administration of fibrin glue and antiplasmin into the thoracic cavity, the pleural effusion did not reaccumulate and there was no evidence of pleuroperitoneal communication by radioactive colloid study. PMID- 1287740 TI - Studies of cancer in migrant populations: methods and interpretation. AB - The use of descriptive epidemiological data (collected without a view to investigating any specific hypothesis) to study the risk of cancer in populations which have migrated from one country to another is reviewed. Place of birth is treated as the risk factor under study in such analyses, although they vary considerably in complexity depending on the availability of information on other explanatory or confounding variables. The underlying assumption of these studies is that migrants undergo a change in their environment (although the extent of this is rarely documented), so that differences in cancer rates confirm the importance of environmental over genetic determinants of risk. Studies which document risk according to time spent in the new country or to age at migration, or differences between migrants and their offspring, add an extra dimension, interpretable in terms of the degree of lifestyle change, or lability of the cancer to changes in exposure to the relevant determinant. Past studies have frequently used rather simplistic methodology, with insufficient attention to the presence of bias, and a reluctance to use standard epidemiological techniques to control for obvious sources of confounding. Migrant studies are divided into four broad categories, depending on the number of comparison groups (two, or more), the availability of a time dimension, and information on exposures; examples of each are described. PMID- 1287741 TI - [Cancer in Japanese migrants to Hawaii: interaction between genes and environment]. AB - This paper describes the progressive changes in cancer incidence that have been observed among Japanese after their migration to Hawaii. It reviews descriptive and analytic epidemiologic data suggesting a role for genetic susceptibilities in explaining the high risk of Japanese for colon cancer and their low risk for lung cancer, when compared to Caucasians. Differences in certain pharmacogenetic polymorphisms may explain these risk patterns. This research may lead to a better characterization of cancer risk at the individual level and, consequently, to improved methods of prevention. PMID- 1287742 TI - Prevention of cutaneous melanoma: an epidemiological evaluation of the Swiss campaign. AB - A national information program, focusing on the main recognized risk factors (primary prevention) and on the potential benefits of early detection (secondary prevention) of cutaneous malignant melanoma, was launched in Switzerland in May 1988. The first campaign, based on a pilot study conducted in 1986 in the canton of Basel, was followed by a recall campaign in July 1989. This report describes the organization of this program and presents an assessment of its initial impact. The number of newly diagnosed cases increased more than twofold (+ 116%) in the two months following the launch of the first campaign (May to June 1988). This trend was accompanied by a statistically significant shift of case distribution towards younger ages (< 60 years; p = 0.003), and a non-significant shift was observed towards less advanced lesions (thickness < or = 1.5 mm). The incidence decreased quickly, though in the twelve month period between the two campaigns it remained 21% higher than before the inception of the program. No appreciable effects were detected from the recall campaign and no difference was seen among regions or between sexes. PMID- 1287743 TI - [Screening for cardiovascular disease risk factors among employees of a hospital]. AB - A health promotion and screening program for the detection of the major risk factors for ischemic heart disease was carried out in 1990 among the employees (n = 4,521; 70% female) of the Centre Hospitalier Universitaire Vaudois (CHUV). The prevalence of risk factors among the 1,425 employees (73% female) who took part in the study (participation rate: males 29%, females 33%) was compared with the prevalence of risk factors within three other populations: 1) new CHUV employees, who are systematically screened (n = 424: 71% female); 2) a representative sample of the general population; and 3) a group of employees from 44 companies located in the same region. Smoking was the most common of the three main risk factors; its prevalence was lowest among CHUV employees and highest among employees of the 44 firms. The prevalence of hypercholesterolemia and high blood pressure was variable among the different populations. These variations could partly be due to differences in methodologies and measurement conditions, but could not totally be explained in this way. PMID- 1287744 TI - [Diabetes mellitus and pancreatic cancer: a case-control study in greater Montreal, Quebec, Canada]. AB - In a population-based case-control study of dietary risk factors in French Canadians in Montreal, a total of 179 cases and 239 controls were interviewed between 1984 and 1988. It was found that the frequency of diabetes was almost three times higher in cases of pancreatic cancer (16%) than in the controls (6%), with an Odds Ratio (OR) of 2.52 and a Confidence Interval (CI) of 1.04-6.11. Fifty per cent of the pancreatic cancer cases had this disease before the cancer was diagnosed, compared with 71% of the controls at the time of the study. Those aged 50 years and over accounted for 75% of the cases and 71% of the controls (diabetic subjects); 68% of the cases were treated with a combination of diet and oral hypoglycemic agents compared with 86% of the controls. Insulin was used by 32% of the cases and 14% of the controls. These results suggest that diabetes may play a major role in the etiopathogenesis of pancreatic cancer in this urban population. A lot of controversy remains about the precise role of diabetes, and further studies are needed for a better assessment and understanding of the mechanisms of this association. PMID- 1287745 TI - [Computer simulation of the 10-year outcome of a cohort of heroin addicts in Ile de-France]. AB - The aim of this study is to develop a computer simulation model to describe imaginary cohorts of heroin users in the Ile de France (greater Paris) region. Because of the lack of well-designed cohort studies in France, this model is based on epidemiological data found in various different studies. The results of the simulation reveal horrifying outcomes in ten years' time: in the more optimistic scenario (an annual non-Aids mortality rate of 1%, an annual rate of permanent addiction curtailment of 10% and a syringe exchange rate of 10%), only 50% of heroin users curtail their consumption permanently without being HIV carriers after 10 years, 16% are HIV carriers and 10% have died. In conclusion, medical care should play an important part in the management of drug users, and secondary prevention aimed at reducing the health problems involved in heroin use should be intensified. PMID- 1287746 TI - [Life style of children and obesity in a population of 5-year-old children]. AB - The increasing level of childhood obesity has prompted some research into the early risk factors likely to lead to preventive measures. A case-control study was conducted of a five year-old population in the Rhone and Isere administrative "departements" of France during the children's first visit to primary school, with the participation of 327 obese children and 704 controls. Anthropometric data on the children since birth, together with data on their lifestyles, were collected in interviews with parents. "Family obesity" and "obesity at birth" were found to be closely related to the child's obesity at five years old (adjusted OR = 2.7 and 2.1 respectively). Of the environmental factors, the hypothesis tested paid specific attention to television viewing, snacks between meals and lack of sleep. These three variables were all found to be risk factors of obesity at five years old. However after allowing for parental obesity, the only remaining significant risk factor for obesity at five was lack of sleep (adjusted OR = 1.4). The pathogenic assumptions raised by these results are discussed. PMID- 1287747 TI - [Sleep disorders and use of psychotropic drugs in 6-year-old children]. AB - The purpose of this prospective survey, conducted over a two years period, was to study the use of psychoactive drugs among six year-old children in the Bas-Rhin administrative "departement", of eastern France. The factors analysed were family environment, after-school time, the child's sleep, the locality where the child lived and the drugs used. The child was examined by school doctors, in the presence of the parents, at the compulsory consultation at the start of first year infant school. The study was exhaustive. Of the 11,274 children examined, 12.1% used a psychoactive drug, although only 1% were considered by their parents to be suffering from insomnia. Of the children using drugs, 32% had used them for more than a year, 24% for more than two years and 11% for more than three years. Consumption was also shown to vary greatly between different localities; in some areas the proportion of children using drugs was more than 50%. PMID- 1287748 TI - [Clinical and molecular basis of androgen resistance]. AB - Androgen resistance is responsible for the development of a spectrum of abnormalities of male sexual differentiation, and can be broadly divided in two categories: deficiency of 5-alpha-reductase and defects in the androgen receptor. Recent developments in the field on molecular biology have allowed the cloning and characterization of the genes responsible for both syndromes and have made it possible to detect the subtle molecular defects underlying these diseases. This discussion will review some of the most recent development in this field of research. PMID- 1287749 TI - [Recent diagnostic and therapeutic aspects in male sexual impotence]. AB - Male sexual impotence is the symptom of an alteration of central and peripheral mechanism neuropsychoendocrine, vascular and neurological. Nowadays it affects 8 10% of sexually active population. In some diseases, like diabetes and uremia, it can reach very high percentages of incidence. At our Andrology Center 35% of referrals are represented by sexual complaints. In the last years the diagnostic accuracy has increased, narrowing the percentage of unknown causes. Vasculopathy represents the most relevant pathological condition associated with impotence: it can affect both arterial and venous vessels. The new medical technologies and procedures permit an increase of the life span but often affecting the quality of life. Therefore, the iatrogenic causes of impotence, both pharmacological and surgical, are growing. A modern diagnostic approach starts with an accurate clinical history and physical examination, followed by an NPT (nocturnal penile tumescence) test and/or ICI (intracavernosal injection) with a standard dose of PGE1 and Doppler flowmetry of penile arteries. An endocrine evaluation (LH, testosterone and prolactin) is also performed. Further investigation of a vascular dysfunction is represented by more invasive procedures, like arteriography, cavernosography and cavernosometry. A suspect of neurological disease is confirmed by sacral evoked potentials. According to the findings of these examinations, a correct therapeutical approach can be applied in 100% of cases. An endocrine treatment is adequate only when a clear reduction of T plasma level or hyperprolactinemia are present. The treatment of other central disorders causing psychoneuroendocrine impotence is promising, but still under investigation. The intracavernosal injection of vasoactive drugs, apart from having revolutionized the diagnostic approach to the impotent patient, represents a clear standpoint in medical management of impotence, particularly in vascular and neurological diseases. The great advancement in the technology of penile prostheses has allowed the development of valuable and reliable tools to be used in selected cases. PMID- 1287750 TI - [Hyperthyroidism during pregnancy]. AB - The authors review the current knowledge of fetus and woman thyroid physiology during pregnancy. They analyze the abnormalities related to hyperthyroidism, and clinical and therapeutic aspects of thyrotoxicosis; in detail possible fetal complications. They suggest the practical management of thyrotoxicosis during pregnancy. PMID- 1287751 TI - Therapeutic strategies in a male with delayed puberty. AB - Therapeutical strategies in male with delayed puberty. Delayed puberty (absence of pubertal modifications after 14-15 years of age) due to transitory deficit of LHRH secretion often constitutes a difficult differential diagnostic problem for conditions of permanent LHRH deficit which can be identified only after 18 years of age in the idiopathic hypogonadotropic hypogonadism. After a period of clinical observation short-term therapy with pulsatile LHRH administration may take place. Therapy can be necessary: to document the functional integrity of the pituitary-gonadal axis; to promote pubertal modification such as to improve and physiologically sustain the patient; to tray a neuroendocrine activation of endogenous LHRH-LH secretion. Also delayed puberty linked to uremia seems to respond to short-term pulsatile LHRH administration. Pulsatile LHRH administration is the most physiological therapeutical approach to subject with delayed puberty. It seems to constitute a valid alternative to the therapy with testosterone or gonadotropins. PMID- 1287752 TI - [Respiratory inductive plethysmography in the functional evaluation of patients undergoing coronary by-pass surgery]. AB - The functional respiratory changes following coronary by-pass surgery were previously evaluated with the traditional spirometric method. Aim of this work is to introduce the respiratory inductive plethismography (RIP), a well known non invasive technique, into the study of those volumetric and ventilatory modifications. Eight cardioischemic patients were selected: all but one were free from pulmonary disorders. The tidal volume, the respiratory rate, the minute ventilation, the vital capacity and the relation between the abdominal and the thoracic part of the ventilatory act, were measured in the pre-intervention session and in the 1st, 3rd and 7th day after the operation of coronary by-pass. In the same sessions, except the 1st day after surgery, the maximal respiratory pressures were evaluated with traditional manometers. The functional changes of the examined parameters, statistically studied with the variance analysis, closely resemble the spirometric modifications registered by other authors. Furthermore the relative contributions of the thoracic and abdominal compartments of the pulmonary ventilation were evaluated, thanks to the non-invasive plethysmographic method. Rip makes it possible to measure the ventilatory pattern and some pulmonary volumes in the very early phases after thoracic surgery, without any trouble for the patient and in a non-collaborative state of consciousness, too. PMID- 1287753 TI - [Diet manipulations and nickel sulphate-induced contact dermatitis evaluated in 24 cases]. AB - The wide distribution of nickel in the environment as well as in animal and vegetable foods has led a large number of authors to investigate the oral absorption of nickel. The aim of this study was to evaluate the effect of a free nickel diet in 24 patients affected by nickel sulphate-induced contract dermatitis. The diagnosis was made on the basis of their past history and of Patch test. A complete remission of symptoms was obtained with a nickel-free diet for two months; Patch test became partial negative in 50% of patients and completely negative in 33%. In conclusion our results confirm the relationship between nickel-induced dermatitis and oral nickel absorption and suggest that diet manipulations can be useful in cases of refractory skin manifestations. PMID- 1287754 TI - [Microparticulate aerosols and respiratory allergy]. AB - The assessment of allergenic activity in submicronic particles could explain some unknown aspects of pollinosis pathogenesis. Twenty-five 0.5 discs have been obtained using a high volume sampler (Hi Vol Andersen) equipped with 0.3 micron Whatman paper filters. These discs have been challenged with a concentrated pool of sera of Parietaria allergic patients by RIA in order to evaluate the presence of allergenic activity on filters. Discs of non sampled filters and discs of sampled filters challenged with serum pool of patients sensitized to house dust mites were used as controls. The percentage of bound radioactivity was detected by gamma-counter. The radioactivity bound to sampled discs with Parietaria sera was 2.3 +/- 0.55 (Standard Deviation); radioactivity detected on control discs was comparable to background values detected by counter. These preliminary date might suggest that submicronic particles of Parietaria can retain some allergenic activity. PMID- 1287755 TI - [An unusual chronic microvasculitis: Goodpasture's syndrome with late myocardial involvement]. AB - We describe a disease, started in a female young adult patient as an apparent pulmonary siderosis, followed nine years later by an extracapillary proliferative nephritis, which developed to uremia in a few months. Later an intra-myocardial vasculitis, responsible of heart failure, appeared. Immune-histochemistry and serological tests exclude a disease mediated by anti-GMB antibodies, and pathologic features suggest a vasculitis mainly affecting lungs and kidneys. PMID- 1287756 TI - A case of vascular purpura with scurvy. AB - A case of vascular purpura of the lower limbs in a 67 year old man is described. A diagnosis of scurvy was made in consideration of the absence of signs of vasculitis on skin biopsy, the history of a diet extremely poor in vitamin C and the prompt resolution of clinical picture with administration of vitamin C. The authors emphasize the importance of taking into consideration scurvy in the differential diagnosis of vascular purpura: this may spare expensive investigations and a dangerous delay in appropriate therapy. PMID- 1287757 TI - [Can alpha-interferon exacerbate a case of mixed cryoglobulinemia?]. AB - We describe a case of exacerbated mixed cryoglobulinemia in a patient previously treated with alpha-interferon, for chronic active hepatitis. The possible pathogenesis of this exacerbated mixed cryoglobulinemia and the relationship between cytokines, hepatitis viral infections and immune reactions is discussed. PMID- 1287758 TI - [Immunotherapeutic approach in tuberculosis: thymus hormones]. PMID- 1287759 TI - Migration stimulation factor (MStF), from murine B cells, constitutively produced by a T-B hybridoma. AB - Hybridomas were established between murine spleen B cells and the thymoma cell line BW5147, to purify the migration stimulation factor (MStF), a molecule likely involved in immunosuppression. The parental B cells were from Lo/PHA mice previously shown to produce high levels of MStF after immunization by appropriate (tolerogenic) doses of ovalbumin. Among the positive clones, B9 was selected, since it produced high levels of MStF constitutively, and no immunoglobulin. This clone was shown to contain the genome of the B-cell fusion partner, since one of its L chain genes had undergone a VK-JK rearrangement. Isolation of MStF by size exclusion chromatography showed 2 major peaks of activity, one of which eluted in a 20-kDa, almost protein-free fraction. This elution is unlikely to correspond to the true molecular mass, since MStF was found not to be a protein. Indeed, MStF was TCA-soluble, thermoresistant, highly hydrophobic and protease-resistant, but activity was abolished by neuraminidase digestion. The possibility of its being a small molecule transported by a protein carrier was also ruled out. These results suggest that MStF is a complex molecule containing both sialic residues and a lipid moiety. Experiments are planned to further investigate the chemical structure of this unusual B-cell factor. PMID- 1287760 TI - How might the K/lambda ratio expressed by antigen-unselected B cells be explained? PMID- 1287761 TI - The virgin B cell K:lambda ratio. PMID- 1287762 TI - Lambda-chain expression of B cells generated in vitro: desire for "immaculate virgin" B cell. PMID- 1287764 TI - Is expression of the B-cell antigen receptor repertoire chaotic? PMID- 1287763 TI - The K:lambda ratio and B-cell development in the foetal liver. PMID- 1287765 TI - [Lymphoproliferative syndrome with granular lymphocytes of CD8+ phenotype: a clonal pathology with a chronic course]. AB - The syndrome of CD8 hyperlymphocytosis with neutropenia is a heterogeneous disorder ranging from reactive benign state to neoplastic pathology. The prognosis for LGL (Large Granular Lymphocyte) leukemia depends likely on its phenotype:-NK phenotype, extremely poor prognosis and rapidly fatal-T phenotype (CD8+), chronic disease with slow progression. Here, we report four cases of CD8+ hyperlymphocytosis with neutropenia, which are CD2+/-, CD3+, CD4-, CD8+, CD16-, CD56+/-, CD57+ phenotype. These lymphocytic proliferations were associated with clonal rearrangement of T-cell receptor b gene. In two cases, characteristic blood hyperlymphocytosis appeared only after splenectomy, but retrospective bone marrow analysis showed that the CD8+, CD57+ lymphocyte proliferation previously existed. These lymphocytes had a low natural killer activity against K562 cell line. HTLV1 proviral sequence was not integrated in leukemic cell DNA. This monoclonal pathology has a chronic clinical course, with a thirteen year evolution in one case. Splenectomy did not correct neutropenia but allowed the control of hemolytic anemia and auto-immune thrombocytopenia in one case. PMID- 1287766 TI - [Incidence of cholesterol embolisms in 70 atheromatous patients hospitalized for cardiovascular evaluation]. AB - Cholesterol crystal embolization must be considered in all atheromatous patients hospitalized for cardiovascular evaluation. Because this is a difficult and often belated diagnosis, between June 1989 and June 1990 a prospective study was conducted on 70 patients. Clinical monitoring, including examination of the fundus oculi, was performed before, and on the 5th day of cardiovascular investigations. The incidence of systemic emboli (12.8%) detected in this way corresponds to that reported in rare published series. Funduscopy is a simple, rapid and little expensive examination which should improve the investigative procedures and point to the best treatment. PMID- 1287767 TI - [Prognostic factors and monitoring of myeloma]. AB - An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment. PMID- 1287768 TI - [Physiopathology of human obesity]. AB - Our knowledge of hunger and bodyweight regulation is gradually increasing. There are wide interindividual variations in nutritional needs and therefore in susceptibility to gross overweight. Obesity is associated with disturbances in neurosensorial, hormonal and metabolic regulations which are now much better understood. Studies of certain ethnic groups in which obesity is particularly prevalent contribute to the genetic approach to the condition. As in animals, where obesity models correspond to mono- or polygenic transmissions, it is probable that in human beings obesity is a syndrome with multiple causes. PMID- 1287769 TI - [Acute non-obstructive necrotizing enterocolitis in adults]. AB - Acute non-obstructive necrotizing enterocolitis in adults is characterized by pathological features: it is an intestinal necrosis beginning in the mucosa, without obstruction of the mesenteric vessels. The disease occurs in a variety of circumstances which may be roughly divided into infections and fall in proximal or distal mesenteric flow rate, the infectious and circulatory mechanisms often coexisting. Little information on the diagnosis is provided by clinical and paraclinical data. Management is medical and/or surgical; it includes alleviation of the symptoms in intensive care unit, attempts at producing local vasodilation whenever possible and resection of the intestinal segment affected. In many cases the diagnosis is made at exploratory laparotomy. The prognosis is poor; it depends on the patient's age, on the extent of the lesions which sometimes require wide intestinal resections, and on the time to diagnosis. PMID- 1287770 TI - [Pyogenic osteomyelitis in Gaucher's disease]. AB - Gaucher's disease is a sphingolipidosis which may be accompanied by severe pain in the bones. We report a case of Bacteroides fragilis osteomyelitis consecutive to surgical biopsy. The bone pain may be due to ischaemia of the bone or to a pyogenic osteomyelitis which is iatrogenic in most cases. The clinical and paraclinical features of these two entities are described after a review of the literature, and the main complementary examinations leading to their diagnosis are presented. PMID- 1287771 TI - ["Spontaneous" hematoma of the psoas in Gaucher's disease]. AB - The authors report a case of iliac muscle haematoma responsible for inguinal pain in a patient with Gaucher's disease type I. This exceptional cause of pain must now be considered side by side with the classical femoral head osteonecrosis and infectious coxitis. Magnetic resonance imaging appears to be the most sensitive and most specific examination for the aetiological diagnosis of hip pain in Gaucher's disease. In the absence of thrombocytopenia and franck abnormality of coagulation, the spontaneousness of the haematoma is discussed. PMID- 1287772 TI - [Septicemia associated with the presence of a pacemaker with endocavitary electrode]. AB - Septicaemia on endovenous pacemaker electrodes is infrequent and difficult to detect. We report the case of a 64-year old woman with a diagnosis of prolonged fever that dragged on for several months before infection of her pacemaker was considered, then confirmed. Repeated Staphylococcus epidermidis isolates from blood cultures were no longer regarded as contaminations, and transoesophageal echocardiography revealed the presence of a "mass" on her endocavitary electrode, which had not been visualized on several previous echocardiographies. Surgical removal of the electrode was soon required in view of multiple septic emboli despite a bacteriologically effective antibiotic therapy. The outcome is favourable after a 6-month follow-up. The authors review the diagnostic and therapeutic problems created by infections on electrosystolic exciting electrodes. PMID- 1287773 TI - [Sarcoidosis and leukemia/T-cell lymphoma associated with HTLV-1 virus infection in adults (apropos of a case)]. AB - The HTLV-1 virus causes a disturbance of the immune system, the evaluation of which is often difficult. We report a case of sarcoidosis in a 49 year old woman of Martinique as evidenced by bilateral hilar adenopathy, hypercalcaemia, uveitis and granulomatous lesions on histological examination. Serological was positive for HTLV-1 antibodies. Three years later she developed an adult T-cell leukemia/lymphoma. The relationships between the HTLV-1 retroviral infection and different pathologies observed are discussed. PMID- 1287774 TI - [Inflammatory rheumatism flare-up after surgical treatment of Cushing's disease: two cases]. AB - The anti-inflammatory effect of natural glucocorticoids is often overlooked, as shown by these two cases of inflammatory rheumatism flare-up which occurred after surgical treatment of Cushing's syndrome. The disorder in the first case was exacerbation of a probable rheumatoid arthritis; in the second case an unlabelled inflammatory rheumatism appeared in a context of postoperative corticotropic deficiency. In both cases a purely substitutive hydrocortisone therapy resulted in dramatic regression of the articular symptoms. It is well known that rheumatismal manifestations may occur in patients with slow adrenal failure. The determinant factor seems to be a glucocorticoid deficiency, either isolated or associated with others, since cortisol exerts and anti-inflammatory activity. In patients with corticotropic deficiency following surgical treatment of Cushing's disease, the endogenous corticosteroid therapy of hypercortisolism is interrupted, allowing the aggravation or emergence of inflammatory rheumatism. PMID- 1287775 TI - [Circulating lupus coagulation inhibitor in two sisters, one with disseminated lupus erythematosus and the other with immunologic thrombocytopenic purpura]. AB - Familial cases of lupus anticoagulant were rarely described. We report the observation of two sisters with lupus anticoagulant, one with thrombocytopenic purpura and the other with systemic lupus erythematosus. PMID- 1287776 TI - [Antiphospholipid antibodies (aPL): detection and clinical significance]. AB - Phospholipid-binding antibodies are heterogeneous immunoglobulins of G and/or M and/or A class which can be detected in association with a variety of pathologies. However they can also occur in the absence of any clinical manifestations. Despite their paradoxical in vitro anticoagulant activity, phospholipid-binding antibodies, either primary or secondary, are frequently associated with venous and/or arterial thrombotic events. Hence, their detection has to be performed in several major clinical situations, cerebral attack, myocardial infarction, recurrent fetal loss, deep vein thrombosis ... Their course has to be controlled at least every six months. Since the incidence of phospholipid-binding antibodies in auto-immune pathologies is high, immunological disorders should also be considered. As yet there is no standardized assay of phospholipid-binding antibodies, either functional with respect to their anticoagulant activity, or immunological (ELISA). It is not established whether they possess an own pathogenic potential or appear as a secondary response following cellular alterations known to be thrombogenic. However it has been suggested that they could participate in the disruption of the hemostatic balance towards procoagulant tendency resulting in thrombosis. PMID- 1287777 TI - [Treatment and monitoring of primary hypothyroidism]. AB - Treatment of primary hypothyroidism requires a long-term hormonal therapy with levothyroxine which restores a normal TSH value. In a series of 192 patients followed up for at least 3 years we tried to evaluate the variability of maintenance dosage and to analyse the factors predictive of replacement dosage. The L-T4 dosage varied from one individual to the other, from 0.6 to 3.2 micrograms/kg. The mean maintenance dosage (118 +/- 38 micrograms/day) was similar in men and women weight for weight, but it was higher in subjects aged under 60 and in those with Hashimoto's or congenital hypothyroidism. There is a positive linear relation between the equilibrium dose and the TSH value (n = 0.84; p < 0.001) and a negative relation with the L-T4 concentration (n = 0.71; p < 0.001). The yearly variation of dosage in each individual was small (about 3.5%) and of the same order as the variation of weight. We conclude that the L-T4 maintenance dosage depends on the cause of hypothyroidism, on the importance of biochemical abnormalities and on the patient's age, sex and weight. In practice, however, the necessary dosage is difficult to predict. In the equilibrium phase the need for replacements is remarkably stable. A yearly assay of baseline TSH seems to be sufficient to evaluate the quality of hormonal compensation in the absence of intercurrent events. PMID- 1287778 TI - [Hemorrhagic tamponade attributed to treatment with antivitamin K]. PMID- 1287779 TI - [Thrombocytopenia occurring during treatment with propranolol]. PMID- 1287780 TI - [Hodgkin's disease diagnosed by surgical bone biopsy: problems of classification]. PMID- 1287781 TI - [Place of inhaled corticoids in the treatment of asthma]. PMID- 1287782 TI - Who gets care? Access to health care as an arena for nursing action. AB - Access to health care in the United States is undeniably inequitable. What should nurses do in the face of increasing gaps in availability of services? The author addresses this question by framing access to health care in its broadest sociopolitical context, positing that access to care is an essential dimension of nursing theory, research, and practice. By offering a conceptual definition of equitable access, providing rationale for the significance of this concept, and critically exploring conditions that limit access to affordable, high quality, nondiscriminatory health care in the U.S., the author lays theoretical groundwork for more effective investigatory and practical action to assure equitable access. PMID- 1287783 TI - Ethical foundations in nursing for broad health care access. PMID- 1287784 TI - A nursing policy perspective. PMID- 1287785 TI - What is access and what does it mean for nursing? PMID- 1287786 TI - Who will pay? The economic realities of health care reform. PMID- 1287787 TI - Nursing's proposal for health care reform. PMID- 1287788 TI - A political perspective on health care access. PMID- 1287789 TI - Qui bono? Nursing education in the context of nursing's agenda for health care reform. AB - Stevens' question "Who Gets Care?" is in the tradition of those arguing for increased access and a more equitable distribution of society's benefits. As such, it provides a framework for nursing scholarship concerned with social as contrasted with individual interventions. Nursing's Agenda for Health Care Reform advances the argument still further by questioning the ideology reinforced by the current system, and offering an alternative system, alternative services and agents. In so doing, the proposed agenda questions the dominant ideology and is, therefore, more accurately a radical departure from the status quo than a reform. While there are some implicit assumptions of both reform and radical change embedded within the work of those addressing a "curriculum revolution," the discussion would benefit from explicit expositions of both the social construction and social function of higher education. PMID- 1287790 TI - Equality vs. individuality: American values in conflict. PMID- 1287791 TI - Equitable access to health care: continuing the dialogue. PMID- 1287792 TI - Engineering and physics in dental technology. Part 3. PMID- 1287794 TI - Communication: the most powerful management skill. PMID- 1287793 TI - Hints and tips in orthodontics. PMID- 1287795 TI - A common sense approach to occlusion. PMID- 1287796 TI - Esthetic tooth arrangement and visual perception. PMID- 1287798 TI - CDT today: new standards for practical examinations -- crown & bridge. PMID- 1287797 TI - Orthodontic treatment for TMJ dysfunction. PMID- 1287799 TI - Surgical stents for osseointegrated implants. PMID- 1287800 TI - A technique for fabricating a reinforced composite splint. PMID- 1287801 TI - CDT today: new standards for practical examinations -- ceramics. PMID- 1287802 TI - Diagnosis of human parvovirus B19 infections by polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used for detecting parvovirus B19 DNA in clinical specimens. A pair of oligonucleotide primers spanning the PstI-fragment of the B19 virus genome was used for PCR, and a PCR product of 727 bp was amplified. B19 virus DNA was detected in all sera (n = 26) of individuals in the incubation period and acute phase of infection. PCR was useful for detecting viral B19 DNA in amniotic fluid and fetal blood of hydropic fetuses, confirming fetal B19 virus infection. PMID- 1287804 TI - Sexually acquired HIV infections: an analysis of epidemiological data concerning cases reported in Sweden 1988-90. AB - 536 Swedish residents who during the years 1988-90 were reported as having contracted HIV through sexual contacts were asked about circumstances regarding the transmission. Answers were received in 411 (76.7%) of the cases (285 homosexual men, 68 heterosexual men and 58 heterosexual women). In 282 (69%) of the cases the persons were without symptoms and in 231 (56%) cases the infection was considered to be < 3 years old. Among homosexual men and heterosexual women the infection was usually acquired in Sweden or Europe whilst heterosexual men more often acquired their infection at casual contacts on other continents. PMID- 1287803 TI - The AIDS epidemic in Tanzania: rate of spread of HIV in blood donors and pregnant women in Dar es Salaam. AB - The prevalence of antibodies to HIV in population groups in Dar es Salaam, Tanzania has been monitored from late 1984 through 1991. In the pregnant women and blood donors the doubling time was about 2 years. If, however, the doubling time is calculated from reported cases of AIDS of the whole country, an average doubling time of 10 months is obtained. We point out factors that may bias calculations of the rate of spread of the virus and thus give rise to erroneous projections for the nearest years, especially the so-called transient effect. It is recommended that serosurveys of representative population groups are carried out at regular intervals. PMID- 1287805 TI - A six-year follow-up of HIV seroprevalence among 300 intravenous drug users in Stockholm. AB - As HIV tests became available in 1984, 300 intravenous drug users (IVDUs) admitted to treatment centres in Stockholm were tested and asked questions regarding their drug use and other risk factors with regard to HIV. At this initial testing, 33 persons (11.0%) were seropositive. Among the 79 heroin users, 28 (35.4%) were positive. The cohort has been followed until 1990 at which time a further 12 seroconversions had taken place. Annual seroconversion rates fell during the study period. The findings support the official statistics showing a fall in new HIV diagnoses among IVDUs during the second half of the 1980's. PMID- 1287806 TI - Clinical and immunological follow-up of previously hospitalized HIV-2 seropositive patients in Bissau, Guinea-Bissau. AB - A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency. PMID- 1287807 TI - Multiresistant Shigella species from African AIDS patients: antibacterial resistance patterns and application of the E-test for determination of minimum inhibitory concentration. AB - The antibacterial resistance pattern and minimum inhibitory concentrations (MIC) of 25 Shigella flexneri, 5 S. boydii, 8 S. sonnei, and 3 strains of S. dysenteriae type 2 isolated from Kenyan prostitutes with bacillary dysentery and AIDS were determined, and the applicability of the E-test for MIC determination evaluated. All strains were resistant to > or = 3 of 9 different antibacterial agents tested. All strains were resistant to tetracycline and erythromycin, 95% to trimethoprim/sulfonamide, 93% to streptomycin, 54% to ampicillin, 39% to chloramphenicol, 2% to nalidixic acid and none to gentamicin and ciprofloxacin. Six different resistance patterns were observed. The most common pattern was resistance to tetracycline, erythromycin, trimethoprim/sulfa and streptomycin (39%). The E-test was shown to be well-suited for susceptibility testing of multiresistant Shigella spp.; the reproducibility was excellent and the correlation with the microtiter dilution method and the disk diffusion method were 98% in both instances. The MIC measured with E-test and the microdilution method were within +/- 1 dilution step for 94.4% of the combinations tested. PMID- 1287808 TI - Clinical features of sporadic Campylobacter infections in Norway. AB - To assess risk factors and clinical impact of campylobacteriosis in Norway, a case-control study of sporadic cases of infection with thermotolerant Campylobacter spp. was conducted. This report describes: (1) the frequency and duration of signs and symptoms, antimicrobial treatment, hospitalization, and faecal carriage among the study patients; (2) diarrhoeal illness and campylobacter carriage among their household members; and (3) antimicrobial susceptibility pattern among bacterial isolates. A total of 135 patients with bacteriologically confirmed campylobacter infection were enrolled in the study. Of these, 58 (43%) were domestically acquired while 77 (57%) were acquired abroad. If the study enrollees are representative of the cases reported to the national surveillance system, the reported infections led to an estimated annual average of at least 8590 days of illness, 78 admissions to hospital, 329 days of hospital stay, 2236 days lost at work or at school, 1000 physician consultations, and 96 antimicrobial prescriptions among the 4.2 million Norwegians. Convalescent carriage of campylobacter was detected in 16% of the patients who submitted follow-up stool specimens; the organism was carried for a mean of 37.6 days (median 31, range 15-69) after the onset of illness. Antimicrobial treatment appeared to have reduced the likelihood of carriage once symptoms had resolved. Diarrhoeal illness was more commonly reported in members of case households than control households (OR = 5.44, p < 0.0001). Cases were more likely than controls to report antecedent recurrent diarrhoea (OR = 6.00, p = 0.034). Two cases of neonatal infection, probably acquired from the mother at the time of delivery, were detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287809 TI - Vaccine immunity to diphtheria: a 20-year follow-up study. AB - A cohort of close to 70 children born in 1967-68 was followed for estimations of serum antitoxin levels against diphtheria. During the first 3-year-period after vaccination the mean level declined from 0.05 international units (IU) to 0.03. From the year before to the year after the booster of 0.5 LF of toxoid was given at the age of 8 years, the mean level raised from 0.01 to 0.06 IU. At 18 years the mean was again down to 0.01. Between 18 and 23 years of age a difference between the sexes was seen (higher levels in men). The explanation of this phenomenon must be the extra booster given to those young men who have done their compulsory military service. PMID- 1287810 TI - Immunoglobulin- and complement-coated bacteria in middle ear effusions during the early course of acute otitis media. AB - We used an immunofluorescence assay to investigate the content of secretory IgA- (SIgA), IgG-, IgM- and C3b-coated bacteria in middle ear effusions obtained within 12-72 h after the onset of acute symptoms of purulent otitis in 28 patients (37 ears). Simultaneously we analyzed the bacteria, both qualitatively and quantitatively, using standard culturing methods and fluorescein conjugated (FITC) antibodies to Haemophilus influenzae and Streptococcus pneumoniae. The ages of the patients were in the range of 5 months to 17 years; 18 were males and 10 females. 73% of the samples harboured no antibody- or C3b-coated bacteria, and particularly those of young patients (< 20 months). 92% of the samples were culture-positive, while 8% showed dormant bacteria. The predominant species were S. pneumoniae and H. influenzae. In 8% of the samples there was heavy and in 11% slight peripheral SIgA-coating of the 5% showed heavy and 19% slight peripheral IgG-coating. Only 3 samples were intensely opsonized, i.e. the bacteria were coated with IgG and C3b simultaneously. In most cases of acute purulent otitis media, the middle ear cavity of young individuals is not able to coat pathogens with SIgA, IgG, IgM and C3b during the early course of infection. PMID- 1287812 TI - Fungal gut colonization with Candida or Pityrosporum sp. and serum Candida antigen in preterm neonates with very low birth weights. AB - To evaluate the diagnostic value of gut colonization by yeasts and of candida antigen in serum for predicting fungal infection in very premature neonates, faecal and serum samples were obtained biweekly from 27 newborn babies treated at our neonatal intensive care unit. Altogether 82 sets of serum and faecal samples were obtained. 17 babies were followed for > or = 4 weeks. Blood cultures, both by routine and lysis centrifugation techniques, were performed for bacteria and fungi if infection was suspected. All children were given systemic broad-spectrum antibiotic treatment. Five of the children died, all without evidence of fungal infection. No systemic antifungal treatments were given. Quantitative faecal cultures demonstrated Candida albicans in 3 (11%) (10(3)-10(5) colony forming units/g) and Pityrosporum sp. in 8 (30%) of the preterm neonates. Candida antigen in titre 4 was detected in 1/82 serum samples. The child subsequently died with no other evidence of candida infection. In 56 full term neonates treated at the intensive care unit during the same period and tested by 1 set of samples, faecal colonization with Candida sp. was detected in 2 (4%) and with Pityrosporum sp. in 4 (15%). None were positive for candida antigen. Fungal gut colonization did not lead to clinical infection in the preterm neonates studied. The false positivity rate of the candida antigen test was low (0.7%). The predictive value of the test could not be determined in this study group with no systemic fungal infections. The role of pityrosporum as an inducer of neonatal infections remains to be evaluated. PMID- 1287811 TI - Lactic acid isomers and fatty acids in sinus secretion: a longitudinal study of bacterial and leukocyte metabolism in experimental sinusitis. AB - Concentrations of the two optic isomers of lactate (D- and L-form) as well as glucose, succinate, acetate, butyrate, isovalerate and valerate were examined in purulent sinus secretions. The samples were obtained from rabbit maxillary sinuses, experimentally infected with Streptococcus pneumoniae or Bacteroides fragilis. More soluble acids such as acetate displayed relatively low levels in the secretion, despite a high microbial production. A substantial increase in D lactate concentration was found in secretions only the first day after induction of pneumococcal sinusitis, and not in bacteroides sinusitis. L-lactate levels were particularly high in secretions of a marked purulent character, and this isomer can be considered as indicator of anaerobic glycolysis in the leukocytes. Less diffusible fatty acids such as butyrate and isovalerate accumulated in the secretion, in spite of a relatively lower production rate, and are thus more reliable indicators of bacterial metabolism. PMID- 1287813 TI - Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system. AB - Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients with acute bacterial or viral meningitis and in AIDS patients with various cerebral disorders. Increased levels of IL-6 were detected in the CSF of patients with bacterial meningitis. On the contrary, most of the samples from patients with viral meningitis (predominantly caused by mumps virus) had no detectable IL-6 activity in CSF. A moderate increase of IL-6 levels was detected in the CSF of AIDS patients with AIDS dementia complex (ADC), progressive multifocal leukoencephalopathy and cerebral toxoplasmosis. Moreover, higher levels of IL-6 were detected in the CSF of patients with cryptococcal meningitis. We conclude that the initial events of CSF inflammation in patients with acute viral meningitis are different from those in patients with acute bacterial meningitis, and the role of IL-6 is less critical to the process. PMID- 1287814 TI - Salmonella paratyphi C osteomyelitis: report of two separate episodes 17 years apart. AB - Osteomyelitis secondary to salmonella infection is well documented in the literature. Infection in more than one focus has also been described. To the best of our knowledge this is the first report of recurrent osteomyelitis in a normal host (a 35-year-old man) with the same organism (S. paratyphi C) in different sites 17 years apart. PMID- 1287815 TI - Long-term oral ciprofloxacin in the treatment of prosthetic valve endocarditis due to Pseudomonas aeruginosa. AB - Prosthetic valve endocarditis caused by Pseudomonas aeruginosa is refractory to medical treatment alone and early valve replacement is necessary. We describe a 40-year-old patient in whom endocarditis developed in the early postoperative period, and reoperation was not considered feasible. Ciprofloxacin was administered orally in order to suppress bacteremia for 36 months. Long-term oral ciprofloxacin may provide an opportunity in the treatment of prosthetic valve endocarditis caused by Ps. aeruginosa in patients who are unfavorable candidates for reoperation. PMID- 1287816 TI - Peritonitis with Mycobacterium fortuitum in a patient on continuous ambulatory peritoneal dialysis. AB - A 35-year-old man on continuous ambulatory peritoneal dialysis (CAPD) developed peritonitis due to Mycobacterium fortuitum and coagulase-negative staphylococci, following an unsuccessful renal transplantation. Infection subsided after removal of the dialysis catheter and treatment with amikacin. Clinicians and microbiologists should be aware of M. fortuitum as a potential cause of peritonitis in patients with debilitating underlying diseases. It is able to grow on ordinary culture media, but detection requires prolonged incubation, and it may be confused with poorly characterized diphtheroids. PMID- 1287817 TI - Aspergillus flavus wound infection following repair of a ruptured duodenum in a non-immunocompromised host. AB - Aspergillus flavus is generally considered to be an opportunistic organism, rarely causing clinical infections in the immunocompetent host. We present a case of a 79-year-old man without history of immunocompromise who developed a severe aspergillus wound infection in an open wound following repair of a traumatic duodenal perforation. Despite aggressive treatment, this invasive infection contributed significantly to his eventual demise. PMID- 1287818 TI - Acquired bisalbuminemia in staphylococcal endocarditis treated with dicloxacillin. AB - An albumin fraction with increased anodal mobility was observed on cellulose acetate electrophoresis, isoelectric focusing, and immunoelectrophoresis of serum obtained 1 month after a 68-year-old male patient had been treated with dicloxacillin for Staphylococcus epidermidis endocarditis. The patient also suffered from rheumatoid arthritis demanding hospital treatment. Normal albumin results from several earlier runs were thus available, and follow-up showed reversion to normal albumin mobility. Treating albumin with dicloxacillin in vitro produced a corresponding mobility increase. PMID- 1287819 TI - Isolated severe thrombocytopenia and bleeding caused by piperacillin. AB - Bleeding and severe thrombocytopenia developed in a 71-year-old man who had been receiving piperacillin 5 g intravenously every 8 h for 9 days for the treatment of Pseudomonas aeruginosa septicemia. After piperacillin was discontinued, the platelet counts became normal. Rechallenge was made with 2 g of piperacillin intravenously resulting in thrombocytopenia within 6 h of piperacillin administration. The platelet count normalized after 3 days when no further piperacillin was given. PMID- 1287820 TI - Chloramphenicol-resistant typhoid fever: an emerging problem in Oman. AB - Until recently multiply drug-resistant Salmonella typhi was uncommon in the Sultanate of Oman. In 1990 the first isolate of chloramphenicol-resistant S. typhi from an Indian expatriate was reported. In 1991, 58 cases of typhoid fever were diagnosed, of whom 19 (33%) were resistant to chloramphenicol. All patients with chloramphenicol-resistant S. typhi are either Indians or Omani with a history of recent travel to India. Chloramphenicol may not be the appropriate blind therapy for such patients. Ciprofloxacin may be the alternative. PMID- 1287821 TI - Increased rate of survival in Streptococcus pneumoniae-infected rats treated with the new immunomodulator Pidotimod. AB - Wistar rats infected with Streptococcus pneumoniae (type III ATCC) rapidly develop an acute form of experimental lobar pneumonia (ELP) with death of 80-90% of the animals by 6 days after the infection. Prophylactic treatment of these animals with the novel immunomodulator Pidotimod, at the dose of 25 mg/kg bw, significantly increased their rate of survival as compared to the control group (50 vs. 90% respectively). Recovery from the infection appeared definitive since all the Pidotimod-treated survivors were alive and in good condition at the end of the observation period (45 days post infection). Prophylactic treatment with higher or lower doses of the drug was ineffective. Therapy with Pidotimod was not effective. This preliminary study suggests that Pidotimod may have contributed to activation of specific and non-specific immune effectors involved in the host response to S. pneumoniae infection. PMID- 1287822 TI - Self-appraisal and coping in out-patients with chronic disease. AB - Self-appraisal, coping efforts, muscle function, and activity and severity of disease were examined in out-patients with rheumatoid arthritis, osteoarthrosis or diabetes mellitus. Factor analysis of a 31-item self-appraisal and coping questionnaire yielded eight factors (self-appraisal, acceptance, minimization, planful problem-solving, avoidance, persistence, attribution of responsibility, and support seeking). For the factors of avoidance, minimization, and persistence, as well as for measures of activity and severity of disease, significant differences between the diagnostic groups were found. For patients with rheumatic arthritis, hierarchical regression analysis indicated disease duration to be associated with acceptance and with attribution of responsibility, and disability measures to be associated with self-appraisal. For patients with osteoarthrosis, they showed disability in muscle function to be associated with avoidance, and more negative self-appraisal as well as lower levels of support seeking to be associated with long disease duration. Results are discussed in terms of structural and adaptive defence forms and of adherence to a coping model ("medical model") which tends to foster acceptance and dependency. PMID- 1287823 TI - Coping behavior of Finnish adolescents: remarks on a cross-cultural comparison. AB - As part of a larger cross-cultural project, the present study analyses the coping styles of Finnish adolescents. A sample of 548 adolescents aged 15 to 17 years was investigated. Coping styles were defined by a matrix of 20 coping strategies applied across eight different developmental areas. Factor analysis revealed a three-dimensional structure of coping styles. The first dimension involves activities such as seeking support or taking advice (Active Coping), the second emphasizes the adolescent's appraisal of the situation and the search for a compromise (Internal Coping/Compromising) and the third includes defenses like denial and withdrawal (Withdrawal) and may be regarded as dysfunctional. The Finnish adolescents most frequently employed functional forms of coping like Active Coping and Internal Coping/Compromising: dysfunctional coping style such as Withdrawal was used less often. In addition, significant main effects for age and gender were found. Girls favored more Active Coping and support seeking behavior, as compared to boys. Both functional coping modes showed an increase with age. A comparison of coping styles across eight different problem areas revealed situation specific influences, too. The discussion compares the coping styles of Finnish adolescents with results of two parallel studies focussing on German and Israeli adolescents, using the same instrument. In spite of the considerable impact of environmental and historical conditions in the three countries, the similarities in coping behavior were impressive. PMID- 1287824 TI - Adolescents' alcohol use related to perceived norms. AB - A questionnaire survey was carried out among 898 Norwegian adolescents age twelve to twenty. The study focused on the relation between adolescents' alcohol use on one side and estimated drinking norms (peers' drinking) together with attributed opinion norms (parents' and friends' acceptance of adolescents' alcohol use) on the other. On average, 5% of students in 7th, 8th, and 9th grade reported weekly alcohol use. They overestimated the number of fellow students using alcohol every week seven-fold. Students' estimates were significantly related to self-reported alcohol use. Even in high-school (10th, 11th and 12th grade) where 29% reported weekly alcohol use, students overestimated number of weekly drinkers among friends and fellow students by two-fold. Contrary to the results from a previous study conducted in Norway, in this study opinions attributed to both friends and parents about adolescents' alcohol use were significantly related to the students' own alcohol use. Estimated behavior norms and attributed opinion norms explained 46% of the observed variance in students' self-reported frequency of drinking. In a health promotion context, these results point to the importance of correcting student misconceptions about how often friends and fellow students drink alcohol. PMID- 1287825 TI - Struggling with self: the personal projects of students seeking psychological counseling. AB - Personal projects can be described as self-articulated goals and related sequences of actions. In order to investigate what kind of personal projects people with psychological problems have, and how they work on them, 28 counselling client students, 44 students of psychology, and 45 students of technology completed a Finnish version of Little's (1987) Personal Project Inventory. The results showed that the clients scored lower on project accomplishment than other groups. Their personal projects were frequently self related, while those of the technology students were often task-related. The higher their sense of coherence, self-esteem, mental health and life satisfaction, the more subjects expected to accomplish their projects, the more frequently they described task-related projects, the less negative affect they reported, and the less frequently they described self-related projects. These results suggest that psychologically distressed individuals struggle with self related projects and have problems in accomplishing their projects. PMID- 1287826 TI - Time perception: effects of sex and sound intensity on scales of subjective duration. AB - Six women and six men reproduced ten time intervals varying in logarithmic steps between 1.3 and 20 s. The durations were indicated by white noise of 10, 25, 40 and 55 dB SL, different sound intensities in different sessions. It was found that (i) greater sound intensity entails shorter reproductions, and (ii) reproductions by male observers are shorter than those by female, although for both (i) and (ii) there is an interaction with the standard durations. The data were treated in accordance with the "parallel-clock model" (Eisler, 1975), whereby the parameters of the psychophysical power function are determined from duration reproduction data. As in previous experiments (Eisler, 1975), the data showed a break in the function entailing two segments. The effect of sound intensity could be attributed to the exponent, which was lower for stronger noise, and the effect of sex to the weight coefficient of the upper relative to the lower segment of the psychophysical function, the coefficient being lower for men. PMID- 1287827 TI - Prevalence studies of problematic behaviors in four-year-olds. AB - Prevalence rates for specific behaviors in the Problem Behavior Questionnaire (PBQ; Behar & Stringfield, 1974) and for four psychosomatically related behaviors (soiling, day and night wetting, and complaints about bodily aches) were estimated in a sample of 377 Swedish 4-year-olds described by their parents (mainly mothers). The results showed that several of the behaviors classified as outgoing conduct problems were common in this age group; boys showed more problematic behaviors than girls, as did children with older siblings. Firstborn children with younger siblings were more fearful and worried. No systematic differences between children in different types of day care were found. Maternal education had no relationship to reported child behaviors. The findings were discussed in terms of the four-year-age period as a period of transition and with regard to different family situations. PMID- 1287828 TI - Preventing childhood accidents in the home: parental behavior to reduce household hazards. AB - The parents of all children between 6 and 18 months in four Norwegian municipalities participated in an investigation to assess to what extent parents take actions to reduce household hazards their children are exposed to, and to identify factors associated with such behaviors. The Health Belief Model was used as a theoretical framework guiding the selection of variables. The results indicate that most parents take considerable action to reduce household hazards. The constructs derived from the Health Belief Model accounted for only a small part of the variance in parental behavior to reduce hazards in the home. PMID- 1287829 TI - Maze-running and thigmotaxis in mice: applicability of models across the sexes. AB - Both male (n = 244) and female (n = 223) Swiss albino mice displayed a U-shaped pattern of thigmotaxis (wall-seeking) in a circular open-field (OF) before and after a daily maze-running. A significant increase of mice's tendency to occupy the inner partitions of the OF after the maze trial on the last three out of five days of training was observed. When factor analyzed, the variables indicating the wall-seeking behaviour of both sexes were divided into two factors interpreted as "spontaneous" in conjunction with the first three to four maze trials and as "learning-related thigmotactic behaviour" during the subsequent trials in the course of the learning process. PMID- 1287830 TI - Single lung transplantation. Surgical experiences with the first seven patients. AB - Seven single lung transplants are reported. The patients were severely disabled and oxygen dependent below sixty years of age with a poor prognosis. Diagnosis were alfa 1-antitrypsin deficiency (3), sarcoidosis (3) and idiopathic emphysema (1). Multiorgan-harvesting including six hearts, was performed in local or distant hospitals (3). Partial cardiopulmonary bypass simplified transplantation. The surgical procedure was modified with a direct transpericardial approach. Soft tissue wrapping by a vascularized pedicle secured the bronchial anastomosis. The four drug immunosuppressive regimen included cyclosporin A, azathioprine, steroids and antithymocyte globulin. Primary graft function was excellent. Six patients survived the postoperative period and are alive 5-19 months post transplant. Transbronchial biopsies and lung function studies have been helpful in detecting pulmonary rejections. Patient rehabilitation is satisfactory in most patients with improvement in physiologic parameters. PMID- 1287832 TI - Factors influencing return to work after aortocoronary bypass surgery. AB - Factors influencing the effect on employment status were investigated in 250 patients (males: females 224:26) who underwent coronary artery bypass surgery between March 1983 and November 1985. The median age at operation was 57.9 (range 36.6-69.4) years and the median follow-up time 32 (19-52) months. Preoperatively 149 patients (59.6%) were receiving sick pay or disability pension because of their heart disease. Only 64 (25.6%) were gainfully employed, in contrast to 97 (38.8%) at follow-up. Of those who were working at the time of operation, all but eight returned to work postoperatively. At follow-up 183 (80.3%) were free from symptoms or much improved, with degree of improvement somewhat greater in those who were working postoperatively. The period of sick leave and the preoperative waiting time were significantly shorter for patients who were working postoperatively than for those who were awarded disability pension. Age, previous myocardial infarction, duration of preoperative angina and type of work were also found to influence postoperative employment status. PMID- 1287831 TI - Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose. AB - In a randomized, double-blind study of patients undergoing elective coronary artery grafting, the effect of heparin-coated circuit combined with 50% reduction of systemic heparin bolus was investigated. Ten patients comprised group HC (heparin-coated) and ten group C (controls). The mean total doses of heparin were 172 IU/kg in group HC and 416 IU/kg in group C and the respective protamine doses were 0.96 and 3.96 mg/kg (both p < 0.001). Activated clotting times during cardiopulmonary bypass were significantly shorter in group HC, and both intra- and postoperative bleeding was significantly less than in group C (7.7 vs. 11.7 ml/kg, p = 0.036, and 6.9 vs. 9.7 ml/kg, p = 0.004). Hemoglobin loss via the drains was 22.5 g in group HC and 43.7 g in group C (p < 0.005). Hemolysis at the end of bypass was significantly greater in group C. Apart from one perioperative myocardial infarction in group HC the postoperative course was uneventful. Use of a heparin-coated circuit is concluded to permit complication-free reduction of heparin and protamine doses and to decrease both intra- and postoperative bleeding, which may favorably influence the outcome of coronary artery grafting. PMID- 1287833 TI - Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment. AB - In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients. PMID- 1287834 TI - Nonpharmacologic treatment of supraventricular and ventricular tachyarrhythmias. A review of 249 consecutive patients. AB - Incapacitating or life-threatening tachyarrhythmias were treated nonpharmacologically in 249 patients from 1982 to 1991. Among 92 patients surgically treated for supraventricular tachycardia the cure rate was 93% and the complication rate 12%. Radiofrequency catheter ablation gave an equal cure rate in 51 patients, but with no major complications or mortality. Direct-current catheter ablation of the His bundle was successful in 96% of 27 patients with drug-refractory atrial fibrillation or other supraventricular tachyarrhythmias. Among 64 patients undergoing surgery for ventricular tachycardia/ventricular fibrillation, the perioperative mortality was 9%, estimated 5-year survival 69% and estimated 5-year freedom from the preoperative arrhythmias 72%. Of 18 patients treated with implantable cardioverter defibrillator, three (18%) died of heart failure during follow-up. Nonpharmacologic treatment of tachyarrhythmias is concluded to be effective and often definitively curative. The safety-risk ratio is improving as new treatment modalities are developed. PMID- 1287835 TI - Myocardial protection by retrograde cardioplegic perfusion in the presence of acute coronary artery obstruction. An experimental study. AB - To investigate retrograde delivery of cardioplegic solutions as a means of enhancing myocardial protection in the presence of coronary artery occlusion, a two-part experimental model was devised. In part 1 (in vitro) the possibility of retroperfusing the entire myocardium during acute occlusion of the left anterior descending artery (LAD) was assessed. In part 2 (in vivo) acute LAD occlusion was performed in dogs, and during 2 hours of aortic cross-clamping crystalline cardioplegic solution was infused at 20-minute intervals. In group I the infusion was antegrade, via the aortic root, and in group II it was retrograde, via the coronary sinus. Thereafter the LAD snare was released and the dogs were weaned from bypass. Delivery of cardioplegia through the aortic root was associated with depression of ventricular function, poor myocardial cooling and severe cellular damage. With the retrograde procedure there was significantly improved recovery of left ventricular function, uniform myocardial cooling and better preservation of cellular morphology. PMID- 1287836 TI - Folded lung: a masquerader of malignancy. AB - Four cases of folded lung were observed over an 8-year period up to 1990. Because of suspected malignancy, three patients underwent exploratory thoracotomy, without subsequent morbidity or mortality, but the fourth patient declined surgery. Although folded lung may have characteristic computed tomographic features, these may be mimicked by carcinoma. If the patient is fit enough, exploratory thoracotomy is advisable in order to establish the diagnosis and permit resection of the lesion, if indicated, while avoiding the risks entailed by false negative CT scan and needle biopsy. PMID- 1287838 TI - Posterolateral diaphragmatic hernia in adults--acute symptoms, diagnosis and treatment. Case report. AB - Acute herniation through a posterolateral diaphragmatic defect is rare in adults. Two cases in which such herniation occurred by sudden inversion, a 29-year-old man and a 17-year-old girl, are presented. The symptoms, diagnosis and treatment are discussed. PMID- 1287837 TI - Continuous extrapleural intercostal nerve block and post-thoracotomy pulmonary complications. AB - To evaluate the effects of continuous extrapleural intercostal nerve block on post-thoracotomy pain and pulmonary complications, a randomized, double-blind, placebo-controlled study was conducted on 80 patients undergoing elective thoracotomy for pulmonary (n = 47) or oesophageal (n = 33) procedures. In patients who received continuous bupivacaine infusion, the requirement for intramuscular opiate and rectal diclofenac was less, the score on a visual linear analogue pain scale lower and recovery of pulmonary function more rapid than in saline-infused controls. Postoperative pulmonary complications occurred in 35% of the saline group, but only 10% of the patients with bupivacaine infusion (p < 0.01). In patients with chronic obstructive airways disease (COAD), the incidence of postoperative pulmonary complications was 54.5% in the saline group and only 4.5% in the bupivacaine group (p < 0.01). Among the patients without COAD there was no significant intergroup difference in such complications. We conclude that continuous extrapleural intercostal nerve block is effective for post-thoracotomy analgesia and reduces pulmonary complications of thoracotomy in patients with COAD. PMID- 1287840 TI - Primary chondroblastic osteogenic sarcoma of the left atrium. Case report. AB - A case of chondroblastic osteogenic sarcoma of the left atrium is presented. The malignant nature of the tumour was not revealed until surgery. It was considered to be nonresectable. At autopsy the tumour was found to be confined to the atrial septum. The possibility of preoperatively establishing the diagnosis and determining the extent of the tumour is discussed. PMID- 1287839 TI - MRI as guide to surgical approach in tuberculous pericardial abscess. Case report. AB - In a 30-year-old man with tuberculous pericardial effusion and symptoms of constrictive pericarditis, 2-D echocardiography indicated localized effusion. Subsequent magnetic resonance imaging showed the effusion to be posterior and compressing the left ventricle. Guided by this information, pericardial resection with drainage of tuberculous abscess was performed via left anterior thoracotomy. PMID- 1287841 TI - Assessment of the lifetime accumulated cadmium intake from food in Kempenland. AB - Research in 1984 indicated that the cadmium body burden was higher in a village where the soil is contaminated with cadmium (Luyksgestel) than in a control village (Zeeland). The distribution of kidney function parameters also differed between the two villages. The aim of this study is to estimate the lifetime accumulated cadmium intake from food for the people from both villages. Various data sets describing dietary patterns in the Netherlands were used. The assessed average lifetime accumulated cadmium intake from food by the study subjects (aged 30-69 years) was 435 mg (+/- 131 mg) in Luyksgestel and 394 (+/- 113 mg) in Zeeland. The estimated lifetime accumulated cadmium intake for a hypothetical allotment gardener of 55 years was 520 mg from vegetables grown on uncontaminated soil, and 655 mg for lifelong consumption of vegetables from contaminated soil. The Luyksgestel subjects' estimated cadmium intake from food was well below the provisional tolerable weekly intake as proposed by the WHO, of 400-500 micrograms or 1124-1404 mg for the lifelong intake by a 55-year-old man. PMID- 1287842 TI - [The value of magnetic resonance tomography in diagnosis and follow-up of cervical spine injuries]. AB - We report upon 12 cases of magnetic resonance imaging of cervical spinal cord injuries, in 8 cases done within 24 h after the injury. We found haemorrhages in the spinal cord in 3 cases, compression of the spinal cord in 3, swelling of the spinal cord in 2, and transsection of the spinal cord and hematoma in the epidural space in 1 case each. A normal MR image was seen in a patient with a complete transverse lesion of the spinal cord. The other 4 MR examinations were carried out between 2 weeks and 8 months after injury or operation. In 2 of these trauma victims interbody fusion of the cervical spine was performed, and the neurological deficit was subsequently worse in both. In 1 patient the course of a haemorrhage within the spinal cord was monitored by MR imaging: 1 image revealed the treatment of a burst fracture of C-7 with an interposed flap from the greater omentum. PMID- 1287843 TI - [Vertebral fractures and abdominal trauma. A retrospective study based on 415 documented vertebral fractures]. AB - 415 spinal fractures were analysed retrospectively. A simultaneous occurrence of vertebral fracture and abdominal trauma was found in 14 patients (3.4%). The mechanism of injury was a fall from a considerable height in 9 cases, a car accident in 3 and a motorcycle accident in 2. Isolated fractures of the transverse processes and rotational injuries of the spine were found to be associated particularly frequently with an abdominal trauma (3 of 14 isolated fractures of the transverse processes = 22%, 5 of 61 rotational injuries = 8.2%), while compression injuries only showed such a simultaneous abdominal injury in 2% of the 300 fractures of this type. We never encountered the combination of distraction injury/abdominal trauma. This is probably because two-point lap-type seat belts are only rarely used in our country. In 2 patients with rotational injuries neurological deficits were observed. The abdominal injuries encountered in our patients were: massive concussion of the kidney (6 cases), rupture of the spleen (3 cases), rupture of the liver (2 cases), rupture of the mesocolon (2 cases), rupture of the caecum (1 case), rupture of a pre-existent aneurysm of the aorta (1 case), rupture of a renal artery (1 case), massive retroperitoneal haematoma (1 case). Other injuries were present in 12 of the 14 patients: 3 craniocerebral injuries, 7 fractures of the long bones, 6 injuries to the thorax and 3 to the pelvis. In conclusion, a simultaneous finding of vertebral fracture and abdominal trauma is rare in our patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287844 TI - [Ultrasound assessment of reconstructed rotator cuffs]. AB - The evaluation of recurrent shoulder symptoms in patients who have had rotator cuff repair is a diagnostic challenge. Pain and limitation of motion may be caused by a recurrence of the rotator cuff tear. Arthrography is not considered to be helpful in postoperative cases, since it is false-positive in most of them. Pre-operative ultrasonography of the shoulder is regarded as a highly accurate diagnostic tool for rotator cuff tears. The diagnostic criteria used are: the continuity of the rotator cuff, its contour, its thickness and its echogenicity. Our study was aimed at determining which ultrasonographic criteria were significant for a retear. In addition, the "normal" postoperative sonographic appearance of the rotator cuff was established. Of 133 patients with a full thickness rotator cuff tear, 110 were evaluated 4-48 months (mean in 21 months) after surgery. A total of 85 cuffs were reconstructed, in 46 cases by direct suture, in 33 cases by suture to the major tubercle and in 6 cases by tendon transfer (Cofield technique). In 25 cases cuffs the could not be reconstructed. Subacromial decompression was performed routinely. The patients were evaluated clinically by range of movement, force and isometric and impingement tests. The subjective outcome was assessed by the algo-functional index of Patte. Ultrasonography was performed using a 7.5-MHz linear scanner. Each sonographic criterion was referred to the clinical and subjective findings. Ultrasonographic evaluation of the rotator cuffs that could not be reconstructed revealed non visualization of the tendons. In 13 of the 85 patients in whom reconstruction of the cuff was possible a normal sonographic pattern was seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287845 TI - [Surgical treatment of dislocated 3 and 4-segment fractures of the proximal humerus]. AB - Twenty-eight three- and four-segment fractures of the proximal humerus were treated by plate fixation (n = 22), screw or Kirschner wire stabilization (n = 5), and primary endoprothesis (n = 1). There were no early postoperative complications. Fourteen months after the operation, 80% of the patients examined showed good results; 4 cases had poor results. In comparison to other reports our results are positive and support plate fixation as the method of choice in these situations. PMID- 1287846 TI - [Osteochondrosis dissecans of the elbow joint]. AB - Thirty-one elbow joints in 29 patients (28 males, only 1 female), operated on for osteochondritis dissecans, were available for follow-up after an average of 10 years. The mean age at diagnosis was 24.4 years, but 11 patients were younger than 20. In 23 out of 29 patients the right elbow was involved, including 2 cases with bilateral involvement. In 20 cases removing the free bodies was the only surgical procedure performed, but in 2 cases it was combined with resection of the radial head. At follow-up, only one-third of the patients had no complaints. Nevertheless, daily activity was not restricted for any of the cases. Degenerative arthritic changes were found in only a few cases. These results are illustrated by means of three typical cases, which are compared with six similar cases in the international literature. PMID- 1287847 TI - [Interlocking nailing of the femur--analysis of problems and errors based on 80 fractures]. AB - A series of 79 patients with 80 femoral fractures stabilized by the Grosse-Kempf interlocking femoral nail system (Howmedica) were critically evaluated for the frequency of problems and technical mistakes during surgery. Problems with patient positioning were negligible. In patients with fractures at a suitable site, the Wittmoser table proved useful. Closed reduction should not be attempted at all costs: in borderline cases, open reduction should be given preference to prevent complications. Radiologically relevant problems included: twisted nails, 27.5% of all cases; broken nails, 2.5%; bent nails, 1.2%. Proximal screws were too long in 18.7%, too short in 1.5%, placed too far cranially in 29.6%, shifted (with damage to the thread) in 3.1%. Distal screws were too short in 11.7%, too long in 16.1%, protruding laterally in 2.9%, malpositioned in 1.4%; affected by ectopic calcifications in 4.4%, by cortical fragmentation in 8.8%, and loosing in 10.2%; both screws broke in one case. Technical mistakes during surgery were faulty assessment of the fracture pattern in 7.5%, a wrong impaction site in 23.7%, and bursting of the proximal fragment in 11.2%. Leg shortening was observed in 8% (16 mm, on average) and lengthening in 11.2% (6.2 mm, on average). Rotational malalignment was seen in 23 of 35 patients followed up clinically: inappropriate external rotation (12.5 degrees, on average) in 12 patients and inappropriate internal rotation (10 degrees, on average) in 11. Implant damage was seen in 8.7%. A breakdown of the complications by the operating surgeons involved clearly shows where the problems lies: 80 fractures were treated by 25 surgeons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287848 TI - [Effects of different intramedullary stabilizing procedures of the femur on lung function in polytrauma]. AB - We investigated the effects of primary (< 24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in multiple trauma patients. The standard procedure following reaming of the medullary canal (AFN) was compared with a new procedure using a small, solid nail without prior reaming (UFN). Pulmonary hemodynamics were determined using a pulmonary artery catheter. Global lung function was assessed by means of the oxygenation ratio (PaO2/FiO2). Concentrations of elastase and the platelet count as a general parameter of the clinical course were determined from central venous blood during and 3 days after surgery. The lung function was stable in UFN patients (n = 6), but decreased significantly in AFN patients (n = 10) from 353 +/- 24 (PaO2/FiO2 preoperative) to 260 +/- 28 (PaO2/FiO2 postoperative) and did not improve until 48 h later. Pulmonary artery pressure (Pap) remained within normal limits in UFN patients, whereas in AFN patients Pap increased from 27.4 +/- 3 mm Hg (preoperative) to 37 +/- 3 mm Hg during reaming and did not normalize until 1 h after insertion of the nail. The platelet count remained unchanged in UFN patients and dropped in AFN patients from 143 +/- 25 x 1000 cells/ml blood (preoperative) to 87.5 +/- 15 x 1000 cells/ml blood 2 days after surgery. Our measurements did not show an increase in central venous triglycerides in the AFN group, probably because bone marrow does not become immediately soluble. There was no significant difference between the increase of elactase levels in the two groups. The femoral nailing procedure with reaming in multiple trauma patients involves a potential risk to the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287849 TI - [Candida infection in the severely burned patient--a successful treatment concept with liposomal amphotericin B]. AB - Candida sepsis is a very serious complication in severely burned patients. This mainly affects patients whose immune system is weakened by illness and/or by drugs. Often diagnosis is difficult because candida sepsis occurs after an initial infection, but therapy is always difficult. Good fungicidal drugs are available, but their side effects limit their effectivity. Two severely burned patients who were suffering from a gram-negative sepsis confirmed by clinical and laboratory data developed candida sepsis. Conventional therapy failed, and both patients suffered from renal failure with constantly high candida-latex-antigen titre. By means of the liposomal encapsulated amphotericin B, which has the same fungicidal effect as amphotericin B, but without its limiting side effects, both, patients could be saved. The kidneys functioned as normal again, the laboratory findings were normal when the patients were discharged. PMID- 1287850 TI - Regulation of G418 selection efficiency by cell-cell interaction in transfection. AB - We attempted to establish the optimum conditions for the calcium phosphate (CaPO4) precipitation protocol by counting G418 resistant (G418r) colonies after transfection of pSV2-neo DNA into BALB 3T3 cells. The amount and molecular size of carrier DNA, number of plating cells, treatment period of DNA-CaPO4 precipitates and expression time of G418 selection were found to be important factors in the induction of G418r colonies. Six G418r clones were derived from BALB 3T3, NIH 3T3 and FRSK cells, and cocultured with G418 sensitive (G418s) parent cells in G418 medium. The colony formation capacity of all G418r cell clones decreased with the increasing number of plated G418s cells. Cell-cell contact appeared to be necessary to reduce the colony formation of G418r cells, and contact-dependent G418r cell killing was probably not related to gap junction formation. Contact-mediated cell killing is a likely explanation for the observation that induction of G418r colonies is often reduced under conditions of high-density plating, long treatment of DNA-CaPO4 precipitates, and long expression time of G418 selection. These results suggest that in some instances transfection efficiency using pSV2-neo DNA should be carefully evaluated because culture conditions can mask the induction of G418r colonies. PMID- 1287851 TI - Characterisation and correction of a mammalian cell mutant defective in late step of base excision repair. AB - An Indian muntjac cell line, SVM, is unusually sensitive to cell killing induced by a range of alkylating agents. Cells transfected with the Escherichia coli ada gene or human genomic DNA have allowed the response of SVM to alkylating agents to be dissociated into two distinct components. Thus, in SVM, which expresses very low levels of alkyltransferase (AT), O6-alkylguanine appears to be the major cytotoxic, clastogenic, and recombinogenic lesion following exposure to agents such as methylnitrosourea (MNU). However, SVM is also very sensitive to agents such as dimethylsulfate (DMS), which produce only very low levels of O6 methylguanine damage. Sensitivity to DMS resides in an inability to complete base excision repair, with the appearance of persistent single-strand DNA breaks (SSBs), and does not appear to involve defects in glycosylase, apurinic/apyrimidinic endonuclease, or DNA ligase activities. Another, possibly related, phenotypic trait in SVM is its limited ability to ligate transfected linear plasmid DNA. Transfectants of SVM, harboring human DNA sequences, show a significant correction of DMS-induced cytotoxicity and clastogenicity and a reduction in the levels of DMS-induced DNA SSBs. The DMS-resistant transfectants have an increased ability to ligate linear plasmid DNA, and also express AT, making these lines resistant to alkylating agents such as MNU. These results suggest that cells possess a mechanism that regulates AT expression, plasmid break-joining ability, and certain aspects of base excision repair. Transfectants of SVM containing human DNA provide a means to isolate genes involved in a coordinate response to alkylation damage. PMID- 1287852 TI - Novel method for isolating mammalian cells defective in fluid-phase endocytosis. AB - A new method for isolating mutants defective in fluid-phase endocytosis has been developed based on the observation that endocytosed horseradish peroxidase can be made lethal to cells. The method was used to isolate a mutant from Chinese hamster ovary cells, termed HRP-1, that was temperature-sensitive for viability and had a 70% reduction in the rate of horseradish peroxidase endocytosis at the restrictive temperature. At high temperature, HRP-1 cells were also defective in the secretory path and their Golgi complex disappeared at the resolution of fluorescence microscopy. These properties are similar to two previously described mutants of CHO cells, DS28-6 and V.24.1. In complementation tests, mutants HRP-1, DS28-6, and V.24.1 all appeared to be in the same complementation group. PMID- 1287853 TI - Efficient selection of mu m-mutants from mu m-expressing myeloma cells by treatment with ricin A-conjugated anti-mu antibody. AB - We have developed an efficient system for obtaining myeloma mutants defective in trans-acting factors required for immunoglobulin (Ig) gene expression. The system consists of a myeloma cell line designed for this purpose and an efficient method for selecting mutants from it. The cell line is X63.653 transfected with the mu gene, whose tailpiece sequence was replaced with the transmembrane sequence of human EGF receptor to hold mu on the cell surface and whose CH1 sequence was removed to prevent mu from being retained in the endoplasmic reticulum. It efficiently and stably expressed mu chains of IgM on the cell surface (mu m+) without light chains. To obtain mutants lacking mu m (mu m-) from the mu m+ cell line by selectively killing mu m+ cells, a method with ricin A-conjugated anti-mu antibody was more reliable than complement lysis mediated by anti-mu antibody. Applying the system, we obtained a variety of mu m- mutants. PMID- 1287855 TI - Near fatality results from health food store sleeping potion. PMID- 1287854 TI - Targeted delivery of antisense oligonucleotides by molecular conjugates. AB - Antisense oligonucleotides efficiently inhibit gene expression in vitro; however, the successful therapeutic application of this technology in vivo will require the development of improved delivery systems. In this report we describe a technique that efficiently delivers antisense oligonucleotides into cells using molecular conjugates. This technique, which was initially developed for the delivery of eukaryotic genes, is based on the construction of DNA-protein complexes that are recognized by the liver-specific asialoglycoprotein receptor. Binding of poly(L-lysine)-asialoorosomucoid (AsOR) protein conjugates with phosphorothioate antisense oligonucleotides to chloramphenicol acetyltransferase (CAT) led to the formation of 50- to 150-nm toroids. Exposure of the antisense molecular complexes (3 microM oligonucleotide) to NIH 3T3 cells genetically modified to express both the AsOR receptor and CAT, inhibited CAT expression by 54%, which was completely blocked by excess AsOR. Equivalent inhibition of CAT activity with purified oligonucleotide alone was observed at a 30 microM concentration. Furthermore, examination of the cells using indirect immunofluorescence for the presence of CAT protein showed 28% of cells exposed to the molecular conjugates lacked any detectable CAT enzyme. Cells exposed to oligonucleotide alone showed a highly variable staining pattern, and only a few of the cells were completely void of CAT protein. Together these data demonstrate that molecular conjugates provide a highly specific and efficient system for the delivery of antisense oligonucleotides. PMID- 1287856 TI - OSHA review, student loans among congressional victories. PMID- 1287857 TI - Senate panel calls for sweeping psychiatric hospital reforms. PMID- 1287858 TI - Texas medical school enrollment increase is most in a decade. PMID- 1287859 TI - Baylor awarded $20 million for prostate cancer research. PMID- 1287860 TI - Researchers study microbes as substitute for animal testing. PMID- 1287861 TI - Accessibility key to compliance under ADA. PMID- 1287862 TI - Physicians vent confusion, frustration over CLIA regulations. PMID- 1287863 TI - Medicare Physician Advisory Committee sets December meeting. PMID- 1287865 TI - Ophthalmologists participating in TDH eye disease program. PMID- 1287866 TI - Toll-free number provides access to Alzheimer's information. PMID- 1287864 TI - TMA takes biennial self-portrait. PMID- 1287867 TI - Agenda on AIDS. PMID- 1287868 TI - Physicians can help victims of violence during examinations. PMID- 1287869 TI - Hepatitis B screening in pregnancy: practical aspects. AB - Hepatitis B may be acquired at birth from a mother who is a chronic carrier and may result in debilitating liver disease later in life. Screening of pregnant women and preventive measures have been shown to be clinically effective and at least marginally cost-effective. The Centers for Disease Control recommends universal screening of pregnant women. Cost-effectiveness has been evaluated using estimated costs and assuming patient compliance. The practical aspects of screening a high-risk population are described in the context of a single program, with discussion of excess costs and problems with implementation. PMID- 1287870 TI - Use of moderate hypothermia during elective craniotomy. AB - Use of moderate hypothermia as an adjunct to elective craniotomy is described in 21 patients. Systemic hypothermia to 32 degrees C was induced by cooling blankets at a mean cooling rate of 1.6 degrees C/min. Patients were rewarmed at the same rate prior to closure of wounds. There were no hypothermia-related complications and the method increased brain relaxation. The rationale for use of this therapy in elective craniotomy and severe head injury is reviewed. PMID- 1287871 TI - Open forum is vital to medicine's unity. PMID- 1287872 TI - Workers' comp: more confusion over dispute resolution. PMID- 1287873 TI - It's what they don't print that counts. PMID- 1287874 TI - Managed care threatens doctor/patient relationship. PMID- 1287875 TI - Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy. AB - We have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p < 0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = 0.61, p < 0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p < 0.01) and endothelial cell outer perimeter (r = 0.65, p < 0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy. PMID- 1287876 TI - Treatment of venous thromboembolism in patients with congenital deficiency of antithrombin III. AB - The treatment course of all thromboembolic events in the patients with congenital deficiency of antithrombin III (AT III) in the national Swedish register was reviewed in order to assess the appropriate medical therapy in this situation. The medical treatment of 70 events of venous thromboembolism was evaluated. There were eight cases with signs of clinical progression. The risk of therapeutic failure with heparin could be as low as 1.5% or as high as 9.2%. It would not be cost-effective to substitute with concentrates of AT III in every case with congenital deficiency thereof in connection with acute venous thromboembolism. "Heparin resistance" does not seem to be a problem in the vast majority of these patients. PMID- 1287877 TI - Effects of heparin, dermatan sulfate and of their association on the inhibition of venous thrombosis growth in the rabbit. AB - This study compares the ability of unfractionated heparin, of dermatan sulfate, and of their simultaneous administration delivered as continuous intravenous infusion or as a single bolus injection to inhibit the growth of a standardized venous thrombosis in the rabbit. When delivered as continuous intravenous infusion for 4 h, heparin and dermatan sulfate inhibited thrombus growth in a dose dependent manner. The maximum antithrombotic effect of heparin was achieved at the dose of 0.15 mg kg-1 h-1 (25 U kg-1 h-1) which generated a mean plasma concentration of 1.8 micrograms ml-1 (0.31 U ml-1) and a 1.8 fold prolongation of the activated partial thromboplastin time (APTT) in comparison to the pretreatment value. A comparable antithrombotic effect was obtained with dermatan sulfate at the dose of 2 mg kg-1 h-1. This dose generated a mean plasma concentration of 30 micrograms ml-1 and a 1.3 fold APTT prolongation. Increasing these doses up to 10 fold did not improve the antithrombotic effect which did not overpass 60-70% of the controls. When the compounds were delivered simultaneously, the maximum antithrombotic effect (64%) was obtained with the following association: 0.06 mg kg-1 h-1 (10 U kg-1 h-1) for heparin and 1 mg kg-1 h-1 for dermatan sulfate. Increasing these doses up to 4 to 5 fold did not improve the antithrombotic effect. Heparin, dermatan sulfate and the association of both were also delivered as single bolus injections and the resultant antithrombotic effect was determined 4 h after saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287878 TI - Tissue factor localization in non-human primate cerebral tissue. AB - Tissue factor (TF), the principal procoagulant of human brain, resides in specific regions of the non-human primate central nervous system. Immunohistochemical studies employing murine anti-human TF monoclonal antibodies (MoAbs) detected TF antigen in the cortex, basal ganglia, cerebellum, and cervical spinal cord in three normal baboon subjects. Although significantly less prominent than human cortical gray matter, a distinct partition of TF in gray matter > white matter was noted. The gray matter predilection of TF was confirmed in primate temporal and parietal lobe cortex by both sandwich ELISA and one-stage coagulation assay. Variation in the relative quantity of TF antigen was observed by ELISA among the three subjects studied. Procoagulant activity followed the pattern of TF antigen (cortical gray matter > basal ganglia > or = cerebellum > cortical white matter), and was 96.5-98.5% inhibitable by a function inhibiting anti-human TF MoAb combination. TF antigen was associated with the microvasculature of all cerebral tissues studied, and spared capillaries most selectively in the cerebral cortex, basal ganglia, and cerebellum. These findings suggest a highly specific ordering of TF antigen and related procoagulant activity in the central nervous system of the baboon, confined primarily to gray matter parenchyma, and to the non-capillary microvasculature. PMID- 1287879 TI - Recurrent, isolated factor X deficiency in myeloma: repeated normalization of factor X levels after cytostatic chemotherapy followed by late treatment failure associated with the development of systemic amyloidosis. AB - We describe the case of a 64-year-old woman with isolated severe factor X deficiency associated with kappa light chain myeloma. At the time of diagnosis there was no evidence for amyloidosis. Complete remission (CR) of myeloma as well as normalization of factor X levels were achieved after cytostatic chemotherapy. Subsequently, factor X deficiency recurred twice without any evidence for relapse of myeloma. The first time factor X normalized again following cytostatic treatment, the second time, however, factor X deficiency was refractory to chemotherapy. Finally, relapse of myeloma became evident associated with rapidly progressing, systemic amyloidosis, which was fatal within a few months. Initially, factor X infusion studies showed a normal recovery, but when amyloidosis became overt the recovery decreased to 0%. We assume that factor X deficiency was due to a binding of factor X to kappa light chains associated with the proliferation of the malignant myeloma cell clone. PMID- 1287880 TI - Lysing patterns of retracted blood clots with diffusion or bulk flow transport of plasma with urokinase into clots--a magnetic resonance imaging study in vitro. AB - Fresh retracted clots are known to be poorly lysable by fibrinolytic agents. We have studied whether lysis of retracted clots could be enhanced by bulk transport in comparison to pure diffusion of plasma containing urokinase (400 IU/ml) into the clots. Cylindrical retracted blood clots were occlusively glued by a polyester into plastic tubes and put in contact with plasma through the clot bases. One group of clots (perfused clots, n = 10) was placed under a pressure difference of 6 kPa (60 cm H2O) which resulted in an average plasma flow of 0.97 +/- 0.34 microliters/min through the clot during the first hour. Another group of clots (non-perfused clots, n = 10) was incubated in the lytic plasma without a pressure difference. Clot sizes were measured during lysis by magnetic resonance imaging (MRI). Channels representing lysed areas penetrated into perfused clots with a velocity of 5.4 +/- 1.6 mm/h (n = 10), whereas the boundaries of non perfused clots subsided with a velocity of less than 0.1 mm/h. Eight of the 10 perfused clots were recanalized after 8 h and the sizes of the perfused group were reduced to 64.0 +/- 10.7% of the initial values. The relative sizes of non perfused clots after 8 h remained significantly higher: 95.0 +/- 1.3%, p < 0.005. In a separate experiment good agreement was obtained between the measured clot sizes by MRI and the residual radioactivity of 125I-fibrin in the clot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287881 TI - Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain. AB - Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7-9, 10-14, 15-19, 28-33, and 37-42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37-42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37-42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37-42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37-42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA. PMID- 1287883 TI - Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation. AB - The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension. PMID- 1287882 TI - Von Willebrand factor, plasminogen activator inhibitor-1 and C-reactive protein are markers of thrombolytic efficacy in acute myocardial infarction. AB - Plasma von Willebrand factor, plasminogen activator inhibitor activity and C reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and > or = 50% resolution of maximal ST-deviation on the electrocardiogram. Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism. PMID- 1287884 TI - Inhibition of platelet adhesion to fibrin(ogen) in flowing whole blood by Arg-Gly Asp and fibrinogen gamma-chain carboxy terminal peptides. AB - We have employed synthetic peptides with sequences corresponding to the integrin receptor-recognition regions of fibrinogen as inhibitors of platelet aggregation and adhesion to fibrinogen- and fibrin-coated surfaces in flowing whole blood, using a rectangular perfusion chamber at wall shear rates of 300 s-1 and 1,300 s 1. D-RGDW caused substantial inhibition of platelet aggregation and adhesion to fibrinogen and fibrin at both shear rates, although it was least effective at blocking platelet adhesion to fibrin at 300 s-1. RGDS was a weaker inhibitor, and produced a biphasic dose-response curve; SDRG was inactive. HHLGGAKQAGDV partially inhibited platelet aggregation and adhesion to fibrin(ogen) at both shear rates. These results support the identification of an RGD-specific receptor, most likely the platelet integrin glycoprotein IIb:IIIa, as the primary receptor responsible for platelet:fibrin(ogen) adhesive interactions under flow conditions, and indicate that platelet adhesion to surface bound fibrin(ogen) is stabilized by multivalent receptor-ligand contacts. PMID- 1287885 TI - The residues AGDV of recombinant gamma chains of human fibrinogen must be carboxy terminal to support human platelet aggregation. AB - The carboxy-terminus of the gamma chain of fibrinogen contains a sequence which is believed to be one of the domains that interacts with glycoprotein (GP) IIb/IIIa to support platelet aggregation. A normal variant of fibrinogen exists in which the four carboxy-terminal amino acids are replaced by 20 amino acids. This variant, known as gamma', has been reported to bind less effectively to platelets. The purpose of the present study was to engineer novel proteins to determine what differences in amino acid sequence between the gamma and gamma' chains influence the interaction of the carboxyterminus with GPIIb/IIIa. In this regard, the gamma chain cDNA in a bacterial plasmid expression vector was modified by oligonucleotide-directed mutagenesis to produce recombinant gamma chains with amino acid changes in the carboxy-terminus which reflect the differences between gamma and gamma'. The recombinant gamma chain with an unmodified carboxy-terminus supported adenosine diphosphate (ADP)-induced platelet aggregation to the same extent as intact fibrinogen. In contrast, the ability of gamma' 427 (the recombinant gamma' variant) and gamma 427 (where the 16 amino acid gamma' extension [412-427] was added to the carboxy-terminus of gamma) to support platelet aggregation was markedly reduced. In addition, the extent of ADP-induced platelet aggregation was decreased in the presence of gamma' 411 (where amino acids 408-411 in gamma were replaced with amino acids 408 411 in gamma'), while gamma 407 (where the four carboxy-terminal amino acids were deleted) was not capable of supporting aggregation. These findings demonstrate that the four residues AGDV are not only required but must be carboxy-terminal to support platelet aggregation. PMID- 1287886 TI - Aurin tricarboxylic acid inhibits platelet adhesion to collagen by binding to the 509-695 disulphide loop of von Willebrand factor and competing with glycoprotein Ib. AB - Aurin tricarboxylic acid (ATA) is known to inhibit ristocetin-induced platelet agglutination but not arachidonic acid-, epinephrine- or ADP-induced aggregation. Its capacity to abolish human von Willebrand factor (vWF)-platelet interactions was further investigated by measurement of platelet adhesion to collagen, platelet agglutination tests and binding studies. In flowing blood using parallel plate perfusion chambers and human collagen, ATA inhibited platelet adhesion to completion in a dose-dependent manner only at the highest shear rate tested (2,600 s-1). It was without effect at 100 and 650 s-1. ATA completely abolished vWF-dependent platelet agglutination induced by ristocetin, botrocetin and asialo vWF, respectively. 125I-vWF binding to ristocetin- and botrocetin-treated platelets, to heparin and to sulfatides as well as 125I-botrocetin binding to vWF was competitively inhibited by ATA. By contrast, binding of 125I-vWF to collagen was not affected. To further localize the domain of vWF interacting with ATA, experiments of inhibition of binding of selected 125I-monoclonal antibodies (MoAbs) to immobilized vWF by ATA were performed. Our data led to the conclusion that: 1) the interaction of ATA with vWF involves sequences of the A1 disulphide loop of vWF (residues 509-695) and close epitopes which interact with GPIb and 2) the inhibition of platelet adhesion by ATA occurs only at a high shear rate where vWF is known to play a key role. Thus ATA, which blocks the vWF/GPIb pathway by interfering with vWF and not with platelets, is a potential tool in preventing the early stages of thrombosis. PMID- 1287887 TI - Biochemical and ultrastructural studies suggest that the effects of thapsigargin on human platelets are mediated by changes in intracellular calcium but not by intracellular histamine. AB - The involvement of intracellular histamine in thapsigargin (Tg)-induced platelet aggregation was studied. Platelet aggregation induced by 0.25 and 0.5 microM Tg was not accompanied by a rise in intracellular histamine but a significant (p < 0.01) increase in the level of intracellular histamine was observed at 1 microM Tg. Preincubation of platelets with inhibitors of histamine metabolizing enzymes had little effect on intracellular histamine levels in platelets stimulated by 0.5 microM Tg. In addition, the inhibitors of histidine decarboxylase (HDC), alpha-methyl histidine (alpha-MH) and alpha-fluoromethyl histidine (alpha-FMH) failed to inhibit Tg-induced aggregation. The intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine. HCl (DPPE), inhibited Tg-induced aggregation but with IC50 values dependent on the concentration of agonist used. The inhibitory effects of DPPE on Tg-induced aggregation were not reversed by the addition of histamine to saponin permeabilized platelets suggesting non-histamine mediated effects of DPPE on Tg induced aggregation. Tg stimulated an increase in the cytosolic free calcium concentration which was unaffected by DPPE indicating that the effects of DPPE are also not due to the inhibition of mobilization of cytosolic calcium. The ultrastructural studies suggest that the major Tg-induced changes (pseudopod formation and granule centralization) are consistent with a primary role for Tg to mobilize calcium; DPPE had very little effect on these ultrastructural changes. The results indicate that the effects of Tg on human platelets are mediated by an increase in cytosolic calcium but not by intracellular histamine. PMID- 1287888 TI - Arachidonate transfer between platelets and lipoproteins. AB - Although platelets have specific bindingsites for LDL and HDL, it is doubtful whether lipoproteins modulate platelet functions via receptor-mediated processes. We investigated platelet-lipoprotein interaction during prolonged incubation with concentrations of LDL and HDL that saturate the bindingsites within a few minutes. When [3H]arachidonate-labeled human platelets were incubated for 4 h with lipoproteins, part of the 3H-radioactivity transferred to LDL and to a lesser extent to HDL. The transfer was temperature-sensitive, unaffected by modification of lysine in LDL or indomethacin treatment of the platelets, and almost irreversible. [3H]arachidonate transfer to lipoproteins could be mimicked by incubating platelets with a high concentration of fatty acid free albumin. This showed, that the loss of 3H-radioactivity reflected a decrease in endogenous arachidonate, leading to impaired aggregation, secretion and thromboxane B2 formation in platelets after stimulation with thrombin but not with arachidonate. Thus, the decrease in platelet functions seen after long incubation with HDL is caused by depletion of platelet arachidonate. Despite an even stronger arachidonate depletion by LDL, this lipoprotein initiated arachidonate metabolism and secretion independent of specific binding sites for LDL on the platelet. Surprisingly, the major part of the secretion was preserved when the formation of prostaglandin endoperoxides/thromboxane A2 was inhibited with indomethacin. These findings argue against a role for LDL and HDL receptors in the modulation of platelet functions and are more in favor of lipid exchange processes between platelets and lipoproteins. PMID- 1287889 TI - Changes in G-actin after platelet activation in platelet rich plasma. AB - We have used the DNase I inhibition assay to study changes in G-actin after platelet activation in platelet-rich plasma (PRP) induced by ADP. Because of problems associated with depolymerization of F-actin after lysis of ADP-activated platelets in the presence of plasma, G-actin was measured using a lysis buffer that contained formaldehyde to prevent any depolymerization of F-actin. Different patterns of response were seen depending on the concentration of ADP used, and these were modified by avoiding aggregation by either not stirring the sample or by adding EDTA. The results show rapid conversion of G-actin to F-actin in association with shape change, and there is a further decrease in G-actin associated with irreversible platelet aggregation. Thus evidence is presented that actin polymerization occurs in two phases after ADP stimulation. PMID- 1287890 TI - Vitamin E binds to specific binding sites and enhances prostacyclin production by cultured aortic endothelial cells. AB - We evaluated the effect of d-alpha-tocopherol (vitamin E) on the production of prostacyclin (PGI2) by cultured bovine aortic endothelial cells. Vitamin E at physiological doses significantly enhanced the production of PGI2 by aortic endothelial cells when added to the culture simultaneously with histamine, the Ca2+ ionophore A23187 (A23187), plasma-derived serum (PDS), or arachidonic acid. This effect was found to occur in a time- and dose-dependent manner, and the maximal enhancement was produced by 9.28 microM of vitamin E for 1 h incubations. Significantly lower amounts of lipid peroxides were measured in endothelial cells stimulated by 10% PDS with 9.28 microM of vitamin E than in those stimulated without vitamin E for over 24 h, although the stimulation during the initial 1 to 12 h period did not have a significant effect on lipid peroxide formation in cultured aortic endothelial cells. We also demonstrated that bovine aortic endothelial cells have specific binding sites for [3H]vitamin E that exhibited time- and temperature-dependent saturability. At 4 degrees C, the nonspecific binding was 8-12% of the total binding, and the specific binding reached equilibrium by 2 h. Specific binding increased with the concentration of [3H]vitamin E and became saturated at concentrations between 1.5 microM and 2.0 microM per 2.0 x 10(5) cells. Raising the unlabeled vitamin E concentration from 97.7 nM to 1,000 microM reduced the specific binding of 2.0 microM [3H]vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287891 TI - Registry of multicenter clinical trials. Twelfth and thirteenth report--1990 1991. The Council on Thrombosis and Haemostasis of the International Society and Federation of Cardiology. The Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. PMID- 1287892 TI - GPIIb/IIIa mediated endocytosis in unstimulated platelets. PMID- 1287893 TI - Acute hepatitis C in haemophiliacs due to "virus-inactivated" clotting factor concentrates. PMID- 1287894 TI - Oesophageal candidiasis in an HIV-negative individual treated with factor VIII concentrate. PMID- 1287895 TI - [How long can a sheep sponge be left in place?]. PMID- 1287896 TI - [Necessity and method of administering minerals in cattle feed]. AB - The soil of cattle farms can differ markedly, thus making it impossible to guarantee that animals receive an adequate supply of minerals. Mineral deficits are expected first in animals grazing pastures on sand, peat and iron-rich clay soils. The quality of the rations can also differ, which underlies the necessity of mineral supplementation. Supplementation is especially necessary when fewer concentrates are given or when more single products are given. Different formulations are often needed on one farm, depending on the feed available and the needs of the animals. In general, too little attention is paid in practice to animals that are not given concentrates. There are different ways of meeting the requirements of the different groups. On the basis of a thorough investigation of farm practices and rations, it can be determined whether supplementation is necessary, and if necessary, how this can be best achieved cheaply and effectively. PMID- 1287897 TI - [An outbreak of keratoconjunctivitis in a dairy farm]. AB - An outbreak of infectious kerato-conjunctivitis is described in a dairy herd during the (winter)stable period. Moraxella was isolated from lacrimation fluid from three animals. The development of the infection was possibly precipitated by a vaccination with modified live IBR virus, adenovirus type 3 and parainfluenza virus type 3. Presumably, climatological-stable conditions play an important role in the clinical manifestation of the infection. PMID- 1287898 TI - [Salmonella dublin on dairy farms in the North of the Netherlands]. AB - During the last century many calves and cows with Salmonella dublin infections are diagnosed in the North of the Netherlands, especially in the province of Friesland. In this paper are retrospectively traced the problems by paratyphoid infections in cattle, from 1919 till now, the diagnosis of which was made at the Animal Health Service in Friesland and North-Netherlands. Over the decennia a decrease is noticed for the percentage of necropsies of calves with S. dublin infections, although some irregular peaks appear. However since 1988 an increase is observed in dairy farms with S. dublin problems, revealing high mortality in calves, abortions and sick cows. PMID- 1287899 TI - [A mongrel Bouvier with otitis externa]. PMID- 1287900 TI - [Pitbulls prohibited since February 1, 1993. Role of the practicing veterinarian in pitbull ban]. PMID- 1287901 TI - [Let us be well]. PMID- 1287902 TI - Ascariasis and childhood malnutrition. PMID- 1287903 TI - The cost-effectiveness of chemoprophylaxis with Maloprim administered by primary health care workers in preventing death from malaria amongst rural Gambian children aged less than five years old. AB - In recent trials in The Gambia, mass chemoprophylaxis with Maloprim administered over several years by primary health care workers to children aged 3-59 months has reduced both mortality and morbidity without inducing impairment of natural immunity or significant development of drug resistance. Taking expenditure of both time and money, by both public authorities and village volunteers, into account, the costs and the cost effectiveness of such mass chemoprophylaxis are estimated here. The cost per child protected per season was (1990 US) $2.84; the cost per childhood death averted was $143. Both costs compare favourably with those of permethrin bed net impregnation. So in some circumstances where malaria is holoendemic, control of childhood malaria by chemoprophylaxis may be more economically efficient than provision of impregnated bed nets. PMID- 1287904 TI - Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria. AB - Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated. PMID- 1287905 TI - An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria. AB - An open paired randomized comparison of intramuscular and intravenous artesunate was conducted in 28 adult patients with severe falciparum malaria. The dose regimen in both groups was 2 mg/kg given immediately followed by 1 mg/kg at 12 and 24 h, and then daily until the patient could swallow. Both routes of administration were well tolerated and there was no evidence of toxicity. One patient in each treatment group died. Clinical and parasitological measures of recovery in survivors were similar in the 2 groups with mean fever clearance times of 37.3 h (standard deviation [SD] = 26.1 h) and 31.5 h (SD = 24.2 h) and mean parasite clearance times of 33.4 h (SD = 13.9 h) and 29.4 h (SD = 12.7 h) in the intravenous and intramuscular groups respectively. Artesunate is equally effective and well tolerated when given by the intravenous or intramuscular routes. PMID- 1287906 TI - Norfloxacin is not effective for treatment of Plasmodium falciparum infection in Kenya. PMID- 1287907 TI - Chloroquine-resistant Plasmodium falciparum isolates from the Sudan lack two mutations in the pfmdr1 gene thought to be associated with chloroquine resistance. AB - Isolates of Plasmodium falciparum from 3 areas of the Sudan were recovered from cryopreservation in London and their chloroquine sensitivity was determined in vitro. Chloroquine resistance was detected in 6/6 isolates from Khartoum, 1/4 from Sennar and 3/3 from Gadarif, indicating that resistance is spreading. All the isolates were sensitive to mefloquine. Studies using blood spots on glass fibre discs and the polymerase chain reaction did not detect two mutations in the pfmdr1 gene, thought to be correlated with chloroquine-resistance, in any of the isolates studied. PMID- 1287908 TI - The effects of multiplication and synchronicity on the vascular distribution of parasites in falciparum malaria. AB - The sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs may cause large discrepancies between the peripheral blood parasite count and the total body parasite burden in falciparum malaria. Despite this, parasitaemia is widely used as an indicator of prognosis and response to treatment. A simple mathematical model describing the changes in circulating and sequestered parasite numbers during acute falciparum malaria is presented. The model uses two parameters only; the standard deviation (SD) of parasite age since merogony (schizogony) as as a measure of synchronicity, and a multiplication factor each 48 h asexual life cycle. The model predicts that during the rising phase of the infection the ratio of circulating to sequestered parasites is dependent largely on the synchronicity of infection rather than multiplication rate, and that in synchronous infections parasitaemias will show considerable fluctuation when the mean stage of parasite development is in the second half of the asexual life cycle. The model fitted well to serial parasite counts from 4 patients with acute uncomplicated falciparum malaria whose infections failed to respond to ciprofloxacin. All four infections were synchronous (SD < or = 4 h), and showed large fluctuations in parasitaemia over short periods related to synchronous sequestration and subsequent reinvasion following merogony. The parasite multiplication rate was determined mainly by the efficiency of merogony or merozoite invasion rather than clearance of circulating parasitized erythrocytes. This suggests that the spleen is relatively inactive during the rising phase of the infection. Quinine treatment did not prevent sequestration but did stop subsequent multiplication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1287909 TI - Polymorphonuclear leucocyte elastase in Plasmodium falciparum malaria. AB - Sixty-one patients with falciparum malaria were studied prospectively to determine the plasma concentrations of the lysosomal proteinase, polymorphonuclear leucocyte elastase (PMN-elastase) and their relationship to disease severity. The patients were divided into 3 groups; severe (parasitaemia > 5%) or vital organ dysfunction (n = 23), moderate (parasitaemia 1%-5% without complications) (n = 15), and mild (parasitaemia < 1%) (n = 23). The mean plasma PMN-elastase level in 10 healthy Thai volunteers was 49.5 (SD = 21.6) ng/ml (range 33-65 ng/ml). Plasma PMN-elastase concentrations on admission were elevated (> 2 x SD above normal) in all patients with severe malaria and were above 100 ng/ml in 86.6% and 65% of the moderately severe and mild patients respectively. PMN-elastase levels during the first 3 hospital days were significantly higher in severe malaria compared with the other 2 groups (P = < 0.001-0.013). The levels decreased as the patients became afebrile and aparasitaemic. Admission plasma concentrations of PMN-elastase correlated directly with bilirubin (rs = 0.50, P < 0.001), serum glutamic oxalacetic transaminase (rs = 0.54, P0.001), parasite count (rs = 0.62, P < 0.001), blood urea nitrogen (rs = 0.54, P < 0.001) and inversely with antithrombin III activity (rs = 0.54, P < 0.001) and the platelet count (rs = 0.58, P < 0.001). Polymorphonuclear leucocyte activation may contribute to the pathogenesis of severe malaria. PMID- 1287910 TI - Increased lymphotoxin in human malarial serum, and the ability of this cytokine to increase plasma interleukin-6 and cause hypoglycaemia in mice: implications for malarial pathology. AB - The origin of illness and pathology in malaria is now largely attributed to high levels of circulating tumour necrosis factor (TNF), released from cells of macrophage lineage after triggering by the products of malarial schizogony. The role of lymphocytes and their products in malarial pathology is not yet known. This paper reports the presence of a related cytokine, lymphotoxin, which is produced only by lymphocytes, in the serum of malarial patients. This is the first report of raised serum levels of lymphotoxin in a systemic disease state. When injected into mice, recombinant human lymphotoxin induced hypoglycaemia and increased serum levels of interleukin-6. These changes, which are seen in severe experimental and human malaria, were also provoked by TNF. Both of these cytokines acted synergistically with interleukin-1, which has also been reported to be raised in malaria, to produce these alterations. These observations imply that lymphotoxin, as well as TNF, may contribute to the hypoglycaemia and raised serum interleukin-6 observed in malaria. This reduces the likelihood of effectively blocking the pathology of this disease by the use of neutralizing antibody directed against just one member of this family of functionally overlapping mediators. PMID- 1287911 TI - Delayed cerebellar ataxia following falciparum malaria: lack of evidence for antibody mediation. PMID- 1287912 TI - Demonstration by the polymerase chain reaction of mixed Plasmodium falciparum and P. vivax infections undetected by conventional microscopy. AB - Mixed malaria infections (Plasmodium falciparum and P. vivax) are suspected to occur at a greater frequency than is detected by conventional light microscopy. To determine this frequency we carried out a prospective 'blinded' comparison of diagnosis by conventional light microscopy and enzymatic amplification of the circumsporozoite gene extracted from dried spotted blood samples. Patients were previously healthy, active duty Thai soldiers assigned to a malaria risk area presenting with malaria. Microscopy (oil immersion objective at 1000 x magnification) involved examination of Giemsa-stained thick and thin blood films by an experienced microscopist. Whole blood samples (25 microliters) dried on filter paper were used for species-specific parasite deoxyribonucleic acid (DNA) amplification by the polymerase chain reaction (PCR) and hybridization with radiolabelled P. falciparum and P. vivax probes. Of 137 consecutive cases of malaria studied, 9% (3/32) of microscopically diagnosed P. falciparum infections and 5% (5/104) of microscopically diagnosed P. vivax infections were found to be mixed by the PCR/DNA probe systems, while 1 case was diagnosed as mixed by both microscopy and PCR. The possibility that malaria patients may have undetected mixed infections should be kept in mind because of the specific therapy required both for P. falciparum and for radical cure of P. vivax. PMID- 1287913 TI - RNA probe detection of Plasmodium falciparum parasitaemia. PMID- 1287914 TI - Role of Anopheles culicifacies sibling species in malaria transmission in Madhya Pradesh state, India. PMID- 1287915 TI - Aminosidine (paromomycin) in the treatment of leishmaniasis imported into the United Kingdom. AB - We report 11 patients with leishmaniasis from different endemic areas, treated in the UK with intravenous aminosidine alone or in combination with other drugs. Clinical and parasitological cures were achieved in all 7 patients from the Mediterranean zone who had visceral disease, with one relapse. Two of 4 patients with cutaneous or mucosal disease were cured; the other 2, from Iraq and Iran, did not respond. Toxic effects were high-tone deafness in 2 patients, one of whom had pre-existing renal impairment, and transient, mild elevation of serum creatinine in 3. Aminosidine is an effective, tolerable and relatively non-toxic alternative to existing antileishmanial drugs for the treatment of visceral leishmaniasis. Further studies will be needed to assess its place in cutaneous and mucosal disease. PMID- 1287917 TI - The identity of Leishmania tropica in Kenya. PMID- 1287916 TI - The isolation and cultivation of Leishmania infantum from apparently normal skin of visceral leishmaniasis patients in northern Pakistan. PMID- 1287918 TI - Incrimination of Phlebotomus (Larroussius) orientalis as a vector of visceral leishmaniasis in western Upper Nile Province, southern Sudan. PMID- 1287919 TI - Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strains. AB - Eleven strains of Trypanosoma cruzi were isolated from patients with Chagas disease in central Brazil by xenodiagnosis and inoculation into newborn mice. Biological characterization and isoenzyme analysis showed that 6 strains were type II (zymodeme 2) and 5 were type III (zymodeme 1). Patients were treated with benznidazole or benznidazole plus nifurtimox. Mice infected with each isolated strain were treated for comparison with the results obtained in the respective patient. Evaluation of cure of the patients was based on the indirect immunofluorescence test, complement fixation reaction and xenodiagnosis. For the mice, haemoculture, indirect immunofluorescence testing, xenodiagnosis and inoculation of blood into newborn mice were used. Tests were performed 3-6 months after the end of treatment. The cure rate was 66-100% in mice infected with type II strains and 0-9% in those infected with type III strains. The correlation between treatment results in patients and mice was 81.8% (9 of 11 cases). Type II strains were more susceptible to treatment, in contrast to type III strains which yielded the majority of therapeutic failures. PMID- 1287920 TI - Direct isolation in vitro of Trypanosoma brucei from man and other animals, and its potential value for the diagnosis of gambian trypanosomiasis. AB - A recently described simple kit for isolating African trypanosomes in vitro (KIVI) was tested further with blood samples from man and other animals in Cote d'Ivoire and Republique du Congo. A high rate of success was achieved, with positive cultures being found 5-36 d after inoculation. The method was also of value in diagnosis. Parasitaemia was initially detected by the haematocrit method; in addition, the mini-anion exchange column was used for human blood and lymph fluid from patients with swollen glands was examined. The card agglutination test (CATT) was applied to the human blood samples. In Cote d'Ivoire, all 5 parasitaemic patients, who were also positive by CATT, yielded positive KIVI cultures. Of 15 animals, 2 parasitaemic and 10 apparently aparasitaemic individuals gave positive cultures. In the Congo, none of the 22 animals was parasitaemic and none gave a positive culture. Of 647 human subjects initially screened, 61, mostly with a positive CATT, were examined by KIVI; 20 gave positive cultures. Seven of these cultures originated from patients in whom no trypanosome had been seen in blood or lymph fluid, although blood from 2 parasitaemic patients failed to yield positive KIVI cultures. Some patients with CATT-negative whole blood and/or serum were positive by KIVI. PMID- 1287921 TI - The use of the acridine orange QBC technique in the diagnosis of African trypanosomiasis. PMID- 1287922 TI - High prevalence of human skeletal muscle sarcocystosis in south-east Asia. AB - The prevalence of human skeletal muscle sarcocystosis in Malaysia was determined by serial examination of formalin-fixed, paraffin-embedded sections of tongue tissues obtained from consecutive, routine autopsies of subjects aged 12 years or more. Of 100 tongues examined, 21% were found to contain Sarcocystis; 66 cysts were found. The number of cysts per case varied from 1 to 13. In one case, 5 cysts were found in a single tissue section. The age range of positive cases was from 16 to 57 years (mean 37.7 years). Prevalence did not differ with regard to race, sex or occupation. The prevalence of human muscular sarcocystosis in our study was higher than that reported elsewhere. Preferential localization of Sarcocystis in tongue or head and neck and/or genuinely high prevalence in south east Asia are possible explanations for this observation. PMID- 1287923 TI - Human infections of Entamoeba chattoni masquerade as Entamoeba histolytica. PMID- 1287924 TI - Entamoeba polecki: human infections in Venezuela. PMID- 1287925 TI - Granulomatous amoebic encephalitis due to leptomyxid amoebae: report of the first Brazilian case. PMID- 1287926 TI - Cryptosporidium: different behaviour in calves of isolates of human origin. AB - The behaviour in calves of 3 Cryptosporidium human isolates was analysed in comparison with a bovine isolate. Twenty-four neonatal calves were infected. An isolate from a patient infected with human immunodeficiency virus (HIV) and showing mild cryptosporidiosis caused severe diarrhoea with a high production of oocysts in neonatal calves, as did a bovine isolate (group 1). Two human isolates, obtained from HIV patients with severe cryptosporidiosis, caused mild diarrhoea with low oocyst production in neonatal calves (group 2). The difference between the 2 groups in numbers of oocysts shed in calves was statistically significant (P = 0.005), as was the duration of oocyst shedding (P = 0.0004). Oocysts of group 2 isolates were less resistant to storage in 2% potassium dichromate at 4 degrees C than were oocysts of group 1. The biological and epidemiological implications are discussed. PMID- 1287927 TI - Human cryptosporidiosis in China. PMID- 1287928 TI - Rapid purification and concentration technique for Cryptosporidium parvum oocysts. PMID- 1287929 TI - Fibre-optic sigmoidoscopy compared with the Kato technique in diagnosis and evaluation of the intensity of Schistosoma mansoni infection. AB - 450 patients in Riyadh, Saudi Arabia, complaining of chronic abdominal pain and, coming from different countries endemic for schistosomiasis, were examined endoscopically using fibre-optic colono- or sigmoidoscopes, and rectal biopsies were examined for Schistosoma mansoni ova. After a preliminary study showed that more than 6 biopsies did not increase the positivity rate, 6 biopsies were taken from the rectum and examined by transparency technique. 280 were positive for S. mansoni, 9 of them having in addition S. haematobium. 4 patients had polyps in the sigmoid colon and rectum. When these positive cases were examined using duplicate 50 mg Kato smears, only 160 (57.1%) were positive. There was a highly positive correlation between the intensity of infection as graded by the 2 techniques. We recommend examination of 6 rectal biopsies using fibre-optic sigmoidoscopy when available in small communities with a patchy distribution of schistosomiasis like Saudi Arabia. The method could also be used to exclude schistosomiasis in persons who have moved from rural to urban or non-endemic areas and are unlikely to be re-exposed to infection. PMID- 1287930 TI - Schistosomal vulval granuloma in a 12 year old Sudanese girl. PMID- 1287931 TI - Validation of a model for variations in Schistosoma mansoni egg counts. PMID- 1287932 TI - Cost analysis of schistosomiasis. AB - Cost analysis of schistosomiasis is important both in assessing the economic impact of the disease and in identifying the most cost-effective approaches to control. Economic impact has been examined both within and without the health sector, but there is a lack of measurement of the effects of disease, or the threat of disease, on patterns of production and community development. The cost effectiveness of control approaches has been examined empirically and by using static models. Future analyses require a stronger epidemiological basis incorporating realistic demography and the temporal dynamics of reinfection, and assessment of outcomes in terms of disease rather than infection. PMID- 1287933 TI - Detection of antibodies and circulating excretory-secretory antigens for assessing cure in patients with fascioliasis. PMID- 1287935 TI - Haemoglobin concentrations and concomitant infections of hookworm and Trichuris trichiura in Panamanian primary schoolchildren. AB - The blood haemoglobin concentrations and intestinal helminth infections were surveyed in 658 children aged between 6 and 12 years attending 4 primary schools in Cocle Province, Panama, in November 1987. 147 (22.3%) of the children were judged to have haemoglobin concentrations indicative of iron-deficiency anaemia. Blood haemoglobin concentrations were significantly lower in children with heavier Trichuris trichiura infections (> 5000 eggs/g) (P = 0.014), and in children with dual infections of both hookworm and T. trichiura (P = 0.005). Children with concomitant T. trichiura and hookworm infections were also significantly more likely to have blood haemoglobin levels indicative of anaemia than children who were uninfected or had single infections with either of these helminths (P < 0.005). In a longitudinal study involving 171 children selected from the original 658, blood haemoglobin concentrations were measured again in November 1988. Children who were considered to show an improvement in both hookworm and T. trichiura infections over this 12 month period showed a significantly greater increase in blood haemoglobin concentrations than children who had remained uninfected with either of these helminths throughout the study period (P < 0.05). PMID- 1287934 TI - Detection of antibodies to secretions of Ancylostoma caninum in human eosinophilic enteritis. AB - To evaluate the role of canine hookworms in human eosinophilic enteritis (EE) in north-eastern Australia, we tested human sera in an enzyme-linked immunosorbent assay (ELISA) which incorporated antigens of adult Ancylostoma caninum. Sera from the following groups were examined: 10 patients with EE (unexplained recurrent abdominal pain and related symptoms, with peripheral eosinophilia) from Townsville and Brisbane; 2 persons known to be infected with A. caninum and 20 presumed unexposed healthy controls; 20 patients with other gastrointestinal diseases; 20 with other identified parasitic infections; and 20 with atopic conditions. High levels of specific immunoglobulin (Ig) G and IgE antibodies were found in patients with EE but not other gastrointestinal disease. Excretory secretory (ES) products were more discriminating than somatic antigens in the ELISA and the IgG/ES-ELISA was the most specific; occasional cross-reactions could be explained on epidemiological or parasitological grounds. The IgM-ELISA was neither specific nor sensitive. We conclude that canine ancylostomiasis is a major cause of human EE in north-eastern Australia, and the pathogenesis is based probably on hypersensitivity to antigens secreted by the parasite. PMID- 1287936 TI - Trichuris trichiura and the growth of primary schoolchildren in Panama. PMID- 1287937 TI - An outbreak of trichinosis in Lebanon. AB - In 1982 an outbreak of trichinosis occurred in an area of south Lebanon consisting of 4 villages, including 6440 persons. In 267 households, involving 2456 persons, typical clinical signs of Trichinella spiralis infection could be recognized among household members. Twenty-one of these households, including 193 persons, were randomly chosen for further studies. Nearly half of the household members (46%) had clinical symptoms consistent with acute trichinosis. 12 of 16 tested persons had high anti-Trichinella antibody titres (12 positive by indirect immunofluorescence (IIF) and 11 by enzyme-linked immunosorbent assay). Class specific antibodies, IIF-immunoglobulin (Ig) G, IgM and IgA, were detected in most tested cases. Of the remaining 4 seronegative cases, 3 had a duration of clinical symptoms < or = 12 d. High peripheral eosinophilic counts (> 20%) were noted in 8 of 16 cases. In total, 15 of 16 cases were positive by one or more of these tests. The outbreak constituted one of the most extensive single outbreaks reported with a calculated > 1000 clinical cases. The cause was attributed to consumption of raw pork meat, an ingredient of kebbeh nayyeh, a favourite Lebanese dish. PMID- 1287938 TI - Strongyloidiasis on the Thai-Cambodian border. AB - A series of children's deaths at a Cambodian refugee camp in Thailand prompted an investigation of children suffering from bloody diarrhoea and severe abdominal pain. Microscopical stool and blood examinations of 15 cases aged 1-7 years revealed hyperinfective strongyloidiasis as the cause of illness. Nine of 14 cases were infected wtih Strongyloides stercoralis, and 6 (42%) had concurrent infection with hookworm. Examination of 958 outpatients at the camp's daily clinic showed that mixed infections of S. stercoralis and hookworm were present in only 4.8% of the outpatients of the same age group. PMID- 1287939 TI - Adverse reactions after community treatment of onchocerciasis with ivermectin in Guatemala. AB - Male and female residents on a Guatemalan coffee plantation where Onchocerca volvulus infections were hyperendemic were offered oral ivermectin (100-200 micrograms/kg) as part of a community-wide treatment programme for onchocerciasis. Forty-five persons were treated and then questioned daily for 28 d about changes in their health. Those with complaints were monitored until all signs and symptoms had resolved. Sixty-seven percent complained of some adverse event after treatment; 60% developed observable adverse reactions attributed clinically to ivermectin. No reaction was life-threatening; the most common were oedema (53%) and fever (47%). Expulsion of intestinal helminths was reported by 38%. Almost all reactions began 24-48 h after treatment; their mean duration was 5 d, despite treatment with acetaminophen and antihistamines. Three patients had oedematous changes lasting over 2 weeks. Incidence, but not severity, of reactions was related to the pretreatment density of microfilariae in skin. PMID- 1287940 TI - Rheumatoid factor and rheumatoid factor isotypes in loiasis with and without accompanying glomerulonephritis. AB - We have studied the distribution of rheumatoid factor isotypes amongst patients with loiasis with and without accompanying glomerulonephritis to determine the possible role of rheumatoid factor antiglobulins in this disease. Our findings indicate an increase in both immunoglobulin (Ig) G and IgM rheumatoid factor isotypes in patients with filariasis alone as well as in patients with accompanying glomerulonephritis. No association with IgA rheumatoid factor was found. The raised IgG and IgM rheumatoid factor levels did not correlate with corresponding IgG and IgM levels. PMID- 1287941 TI - Salivary and urinary diagnosis of human immunodeficiency viruses 1 and 2 infection in Cote d'Ivoire, using two assays. AB - This investigation, done at the Institut Pasteur de Cote d'Ivoire 'blind' of the previous serological findings, suggests that GACELISA, a commercial immunoglobulin G capture enzyme immunoassay for anti-human immunodeficiency virus antibody, can be successfully applied to unprocessed saliva and urine specimens. Its accuracy may be as high as that of conventional enzyme assays on serum tested under similar conditions. However, the role of GACPAT, a similar assay, as a cheap alternative screening test for urine remains in doubt unless its non specificity can be controlled. PMID- 1287942 TI - Complement pathway activity in serum from patients with classical dengue fever. AB - Complement activity in 125 cases of classical dengue fever was examined through the measurement of haemolytic activity. During the first 3 d of fever, the classical complement pathway activity (CCPA) was not altered in 109 cases. After 4 d of fever, 9 of 16 patients in the viraemic period had CCPA decreased by 45% (995 +/- 119 units/ml) and serum complement component C4 decreased by 40% (10.4 +/- 0.9 mg/dl). The alternative complement pathway activity was not affected in any case tested throughout both viraemic and convalescent stages. Both CCPA and C4 persistently decreased in 3 of these 9 patients at the convalescent stage. A decrease in serum C3 was also observed in these 3 patients only, and circulating immune complexes (CIC) levels were particularly high in these 3 patients. These results indicate that there is little evidence of complement activation on days 1 3 of viraemia but that complement activation may occur subsequently. It is concluded that both CIC and other unknown factors not related to CIC may contribute to complement activation in some cases (9/125) of classical dengue fever. PMID- 1287943 TI - Duration of immunoglobulin M antibodies against Rift Valley fever virus in cattle after natural infection. PMID- 1287944 TI - Serological evidence in sheep suggesting phlebovirus circulation in a Rift Valley fever enzootic area in Burkina Faso. AB - Within the Phlebovirus serogroup, Rift Valley fever (RVF) virus is endemo enzootic in the African sahelian zone. Recently an RVF epizootic in West Africa prompted a serosurvey in the major sheep and cattle raising areas. Because of the close antigenic relationship between the phleboviruses it appeared of interest to evaluate the prevalence of the other phleboviruses also. In 1987, 482 sheep serum samples were collected in 2 different ecological zones of Burkina Faso and tested for the presence of phlebovirus antibodies. A sensitive but non-specific immunofluorescent antibody test and a specific enzyme-linked immunosorbent assay (ELISA) were used, with the following African phlebovirus antigens: Rift Valley fever (RVF), Arumowot, Gabek Forest, Gordil, Saint Floris and Odrenisrou. A total of 15.8% of the sera sampled had anti-RVF antibody in the ELISA. RVF virus appeared to be more active in drier areas such as the sahelian region, known to be an enzootic area for the disease. Antibodies to other phleboviruses were found in 11.8% of the samples, independent of RVF virus activity. It is assumed that sheep can be infected by different phleboviruses. PMID- 1287945 TI - Septicaemic melioidosis: a review of 50 cases from Malaysia. AB - Fifty cases of septicaemic melioidosis were reviewed. There was a preponderance of disease among males (male:female ratio 3.2:1) and those aged over 30 years. The presenting clinical features were very varied and not pathognomonic, ranging from fever, cough and septicaemia to fulminant septicaemia and shock. Pulmonary involvement was recorded in 58% of the patients. Skin and soft tissue sepsis was seen in 24%, but many had signs and symptoms of multiorgan involvement. Associated underlying illness was identified in 76% of patients, diabetes mellitus being the commonest (38%), while 34% had more than one predisposing factor. The mortality of 65% in our series is a reflection of the less than satisfactory status of the diagnosis and therapy of septicaemic melioidosis. Only 24% of our patients received appropriate empirical antibiotic therapy. A high index of suspicion of melioidosis in endemic areas and the use of appropriate empirical antimicrobial therapy would be a step towards reducing the high mortality rate. PMID- 1287946 TI - Does antibody to mycobacterial antigens, including lipoarabinomannan, limit dissemination in childhood tuberculosis? AB - Serum immunoglobulin (Ig) G responses to a variety of mycobacterial antigens were measured in children from the UK, in children with tuberculosis from Hyderabad, India and Dhaka, Bangladesh, classified according to whether the disease was disseminated or localized, and in non-tuberculous controls. Anti lipoarabinomannan (LAM) IgG responses in UK children showed a marked trough between 6 months and 3 years coincident with the reported peak incidence of disseminated tuberculosis. Geometric mean IgG responses to sonicates of slow growing mycobacteria (rich in LAM) in 36 children with disseminated tuberculosis were markedly lower than in 99 children with localized tuberculous lesions (for Mycobacterium scrofulaceum P < 0.01, for M. tuberculosis P < 0.01, and for M. vaccae P < 0.01). Responses to purified LAM were also lower in the disseminated tuberculosis group (P < 0.05) but there was no difference between the groups in their response to mycobacterial 65 kDa protein. Multiple regression analysis showed that the reduced response to sonicated mycobacterial antigens and to LAM in children with disseminated disease was independent of age, nutritional status, skin test reactivity, duration of previous symptoms, and city of origin. There was no evidence for sequestration of antibody to immune complexes. These findings are compatible with the hypothesis that children with low levels of antibody to sonicated mycobacterial antigen and to LAM, or those who cannot mount an antibody response, are predisposed to dissemination. A role for antibody in preventing disseminated forms of tuberculosis in childhood has implications for the development of improved vaccines and for the optimum timing of vaccination with bacille Calmette-Guerin. PMID- 1287947 TI - Bacterial pathogens isolated from guppies (Poecilia reticulata) used to control Aedes aegypti in Trinidad. PMID- 1287948 TI - Hospital admissions of Aborigines and non-Aborigines in Western Australia, 1977 1988. AB - Aborigines were admitted to hospital in Western Australia 2.8 times as frequently as other persons in 1977-1988. Their highest relative admission rates were in the 0-5 years age group, mostly for respiratory and gastrointestinal infections. Relative admission rates (all ages) for some categories were: infectious and parasitic, 4 to 10-fold; respiratory, 5-fold; nervous system, 4-fold; injury and poisoning, 3 to 5-fold; mental disorders, double the non-Aboriginal rate. Admissions for respiratory illnesses were consistently much higher in Aborigines of all ages. There were some significant declines in relative hospital admission rates for Aborigines over the study period. PMID- 1287949 TI - Leishmaniasis and 'Desert Storm'. PMID- 1287950 TI - Treatment and care of pet pigs. PMID- 1287951 TI - Introduction and spread of thermophilic campylobacters in broiler flocks. AB - Campylobacteriosis is the most commonly reported infectious cause of human gastroenteritis in developed countries and broiler chickens are considered to be the major food-borne source of the infection. The control of the infection in man depends upon its control in broiler flocks but the epidemiology in poultry is poorly understood. Up to 50 per cent of broiler flocks may be infected and most of the birds in an infected flock carry the organisms until slaughter. Vertical transmission through the egg appears unlikely but there are many other potential sources of the infection for the chicks; direct contact with infected animals or birds has been proposed and there is also evidence for indirect transmission through drinking water or insect vectors. It is suggested that the cross sectional studies discussed in this review should be followed by well designed case-control studies to test the aetiological hypotheses put forward. PMID- 1287952 TI - Induction of parturition in dairy cows with dexamethasone. AB - Sixty Holstein cows were paired by parity and sire, and one of each pair was allocated at random to treatment or control; 17 cows were injected with 7.5 mg/100 kg dexamethasone trioxa undecanoate 14 days before the predicted date of calving, 13 cows received the same dose five days before term and 30 cows were left untreated. The treatment significantly advanced parturition and 29 of the 30 induced cows calved within 72 hours of the injection. Induction at day 14 before term was safe for calf and dam, the calves were 3.2 kg lighter than control calves and there was a high incidence of retained placenta. Treatment for this condition resulted in increased veterinary costs of 14.50 pounds per cow exclusive of dexamethasone treatment. Treatment at this stage was also associated with low pregnancy rates in the next breeding season. Calves born after induction at five days before term were not significantly lighter than calves from control cows, the problem of retained placenta was less marked and there were no subsequent effects on fertility. There were no significant effects of induction on milk yield or milk quality up to 200 days of lactation. PMID- 1287953 TI - Appraisal of teachers in the Faculty of Veterinary Science, University of Liverpool. AB - In 1988, the Faculty of Veterinary Science, University of Liverpool, introduced a system of teacher appraisal, following the report of a faculty working party. The system is designed to provide information which will help the personal development of teaching skills, and also to provide the information required by the university for promoting a lecturer to senior lecturer. It incorporates opinions from students, collected formally by means of questionnaires, and from personal peers chosen by the lecturer, and a self-appraisal record which forms the basis of an annual review from the head of department. Official peers, drawn from both the veterinary faculty and the department of education and extension studies, are trained and used in pairs, to assess and report on staff eligible for promotion. The system has been evaluated by a research assistant funded by the University Funding Council. PMID- 1287954 TI - Chronic contagious ecthyma and caseous lymphadenitis in two Boer goats. PMID- 1287955 TI - Contagious caprine pleuropneumonia in Ethiopia. PMID- 1287957 TI - Identification of pit bull terriers. PMID- 1287956 TI - Chinese shar pei fever syndrome: a preliminary report. PMID- 1287958 TI - Policy on welfare. PMID- 1287959 TI - Control of sheep scab. PMID- 1287960 TI - Evening primrose oil and epilepsy. PMID- 1287961 TI - Policy on welfare. PMID- 1287962 TI - Casualty slaughter. PMID- 1287963 TI - Intra-operative use of NSAIDs. PMID- 1287964 TI - Mycotoxicosis in cows. PMID- 1287965 TI - Technetium licensing. PMID- 1287966 TI - A study of major causes and types of poisoning in Khonkaen, Thailand. AB - To investigate the problem of poisoning in Khonkaen Province, Thailand, a prospective data collection method was used. From 257 acute poisoning cases, the total poisoning rate was found to be 0.76/1000 hospital visits and the case fatality rate was 2.7%. Major types of poisoning found were poisonous animals (28.8%), agricultural chemicals (27.2%), misused therapeutic drugs (19.0%) and household chemicals (10.1%). Major causes of poisoning were suicide attempts (35.4%), accidents (28.4%), ignorance (26.8%) and occupational (8.6%). The most frequent age group affected was 11-30 y (58.8%). Females were found involved more than males (1.2:1). In males, the most frequent cause was unintentional poisoning; in females, it was from suicide attempts. The most frequent types among males were poisonous animals and agricultural chemicals; in females they were agricultural chemicals, misused therapeutic drugs and poisonous animals. The poisoning rate in children 0-5 was 12.1% of the total cases, and poisoning from every type of toxic substance was found. The cause in children was unintentional poisoning. The peak total poisoning time was from August to October. PMID- 1287967 TI - The acute toxicity, primary irritancy and skin sensitizing potential of glutaric anhydride. AB - Glutaric anhydride (GA), an industrial chemical, was found of moderate acute peroral lethal toxicity with LD50 values (95% confidence limits) in the rat of 1.41 (0.80-2.49) g/kg (males) and 0.54 (0.36-0.79) g/kg (females), with death being due in part to gastrointestinal irritancy. Dilution with water given by gavage after peroral dosing had no effect on lethal toxicity. Acute percutaneous LD50 values (rabbit) by 24-h occlusion were 6.25 (5.34-7.33) g/kg in males and 5.66 (3.21-9.95) g/kg in females; local skin effects included erythema, edema, necrosis and ulceration. A 6-h exposure to a statically generated saturated vapor atmosphere (rat) produced no signs of toxicity or irritancy. A 4-h, but not 1-h or 3-min occluded contact with 0.5 g of moistened GA (rabbit) produced erythema, edema and necrosis. Contamination of the eye (rabbit) with 10 mg GA produced conjunctivitis (hyperemia, chemosis and discharge) which persisted 7 to 14 d, mild iritis of 2 to 14 d duration, and mild to severe corneal injury which healed within 14 d. A maximization study in guinea pigs by the method of Magnusson and Kligman showed no potential for skin sensitization with GA. The major acute hazards of GA were by swallowing, eye contact and sustained skin contact. PMID- 1287968 TI - Carbaryl distribution in rabbit tissues and body fluids. AB - After single po administration of 14C-naphthylcarbamate, liquid scintillation assays evaluated the distribution of carbaryl in rabbit serum, liver, kidneys, small and large intestine, spleen, heart, muscles of the thigh and lungs and its excretion in urine and feces at 2, 4, 6 and 8 h after dosing. At 2 and 8 h radioactivity was not observed in spleen, heart, muscle and lungs, while all other tissues had increased values up to 6 h. The main excretory pathway of carbaryl was the kidneys. PMID- 1287969 TI - The immune response of sheep to subclinical chronic exposure to the herbicide Bentazon TP. AB - A study of the effect of the Czechoslovakian herbicide BENTAZON TP on cells of the sheep immune system was carried out over a 3-mo period. A temporary decline in the number of T-lymphocytes in the peripheral blood was seen after 6 w of daily feeding of the herbicide. Dose-dependent statistically significant changes in the leucocyte migration index (p < 0.05) were seen at daily doses of 1/10 the LD50 (195 mg/kg body weight) and 1/20 the LD50 (97.5 mg/kg body weight) the 8th and 10th w of feeding, respectively. Significant changes of phagocytic activity and in the phagocytic index were not observed. PMID- 1287970 TI - Characterization of rumen bacterial pyrrolizidine alkaloid biotransformation in ruminants of various species. AB - An in vitro assay was used to examine biotransformation of toxic Senecio jacobaea pyrrolizidine alkaloids (PA) in ovine, bovine, and caprine rumen contents. Pyrrolizidine alkaloids were analysed by high performance liquid chromatography, and the rates of the alkaloid biotransformation were determined. The microbiological "Most Probable Numbers" technique was also used, in combination with thin-layer chromatography, to estimate relative numbers of rumen PA biotransforming bacteria in the same samples. Pyrrolizidine alkaloids were biotransformed at average rates of 2.9 micrograms/ml/h (bovine), 25.6 micrograms/ml/h (caprine), and 19.2 micrograms/ml/h (ovine). Estimates of numbers of PA-biotransforming bacteria were 1.1 x 10(7) bacteria/ml rumen contents (bovine), 2.4 x 10(7) bacteria/ml (caprine), and 3.0 x 10(7) bacteria/ml (ovine). This project is among the first to quantitate rates of PA biotransformation in rumen contents and to identify caprine and bovine, in addition to ovine, rumen PA biotransforming activity, as well as to estimate the actual numbers of PA biotransforming bacteria in rumen contents. PMID- 1287971 TI - Effect of soil on aflatoxin tissue retention in chicks when added to aflatoxin contaminated poultry rations. AB - The effects of silty clay loam soil on aflatoxin B1 (AFB1) absorption were investigated when added to the diets of chicks fed aflatoxin-contaminated rations. Sixty 1-d-old White Leghorn chicks were fed a control ration (< 5 ng AFB1/g), a low aflatoxin-contaminated ration (55 ng AFB1/g), a high aflatoxin contaminated ration (4,488 ng AFB1/g), or high aflatoxin-contaminated rations (4,488 ng AFB1/g) + 25% or 50% soil. Livers in each group were pooled and analyzed for AFB1 and metabolites. The addition of soil significantly reduced the levels of AFB1 in the livers, although the reduction was less when 25% soil was fed compared with the 50% soil feeding. PMID- 1287972 TI - Exchange transfusion in a case of severe theophylline poisoning. PMID- 1287973 TI - Clinical studies of employees in a sheet-forming process at a paper mill. AB - Formaldehyde resins are used to improve the wet strength of paper. During the sheet-forming process of paper manufacture, formaldehyde fumes are liberated. Twenty-two male subjects having such exposures in a paper mill and 27 unexposed subjects were clinically evaluated to determine the effect of low level formaldehyde exposure in a tropical country. The workers were exposed to 0.03 mg formaldehyde/m3 air as an 8-h TWA. Formic acid excretion in urine was 37.2 +/- 18.9 and 20.3 +/- 4.2 ug/L among the exposed and the unexposed subjects, respectively. Significantly more respiratory problems (31.8%) were observed among the exposed subjects as compared to controls. Complaints pertaining to gastrointestinal, musculoskeletal and cardiovascular systems were also more frequent in exposed subjects. In spite of formaldehyde concentrations being well within the prescribed ACGIH limits of 1 ppm, the high rates of sickness emphasise the need for detailed studies on formaldehyde-exposed subjects in tropical countries. PMID- 1287974 TI - Snakebites in poultry. AB - Eight cases of snakebite involving 5 flocks were seen in chickens, ducks and turkeys in the Avian Ambulatory Clinic of the Veterinary Teaching Hospital, Zaria, between July 1983 and August 1990. Most of the clients resided in areas with large canopies of trees and bushes. There was a large gully just behind the residential areas. Twenty-one birds were bitten; chickens constituted 85.7%, turkeys 12% and ducks 4.8% of this number. Hens incubating eggs were most vulnerable. Cocks were usually bitten when they attacked the snakes. Clinical signs were similar to those reported in other animal species. Gross lesions included congestion of visceral organs and hemorrhage in the viscera, around the bite sites and in the sc tissues. There was also im edema around bite sites. The fatality rate was 87.5%. PMID- 1287976 TI - Plant nurseries: a reliable resource for plant identification? AB - Poison Centers frequently rely on the assistance of local plant nurseries to identify unknown plants involved in exposures. The reliability and accuracy of utilizing this method has never been studied; therefore, our objective was to evaluate this primary resource of plant identification. A study was done in which callers were instructed to take plant samples to a local nursery for visual identification. Once the patient was treated according to our normal protocol, the plant specimen was sent to a botanist for a second identification. The botanist provided his identification results through a blinded process. The collected data was gathered from 68 cases that completed the necessary study criteria. In 58% of the cases, plant nurseries were an unreliable source for plant identification. These incorrect identifications resulted in the "undertreatment" in 24% of the exposures. PMID- 1287975 TI - The biological activity of glyphosate to plants and animals: a literature review. AB - Glyphosate is a widely-used broad-spectrum herbicide with little to no hazard to man or the environment. Glyphosate is highly effective against 90 kinds of emerged grasses, brush and broad-leaf weeds. There is no residual soil activity, it does not leach into non-target areas, and it is non-volatile. It is practically nontoxic to mammals, birds and fish, showing no bioaccumulation in the food chain; it is biodegraded into natural products. When used correctly, glyphosate poses no threat to the environment and its inhabitants. PMID- 1287977 TI - Alterations of libido in gased Iranian men. AB - This investigation was done on 800 Iranian men who survived the immediate hazards and lethal phase during chemical warfare exposure. At the time of interview they had gone back to their usual lives. Men injured with chemical weapons containing mustards may have impotency and loss of or decreased libido. PMID- 1287978 TI - Acute renal failure from the ingestion of toxic plants. PMID- 1287979 TI - Oleander poisoning in cattle of the Fars province, Iran. PMID- 1287980 TI - Orientation selectivity of 3-month-old infants. AB - A modification of the visual evoked potential (VEP) technique, first employed by Braddick, Wattam-Bell and Atkinson [(1986) Nature, London, 320, 617-619] was used to estimate the orientation selectivity of 3-month-old infants. The orientation selective VEP was recorded in response to various changes in the orientation of a square-wave grating. The magnitude (the square root of the power of the FFT) at the frequency of orientation change was assumed to represent the response to the change in grating orientation. Orientation sensitivity was then estimated by plotting the magnitude of the FFT at the frequency of orientation change as a function of the log of the orientation change in degrees. For each individual, the data were fit by nonlinear regression and threshold was defined as the largest orientation angle for which the magnitude of the FFT was zero. The results suggest that the orientation selectivity of 3-month-old infants (1.33 deg) is similar to that of adults (1.13 deg) tested with the same stimulus parameters (1 c/deg, 9 Hz). However, when adults are tested with stimulus parameters selected to optimize their VEP response (4 c/deg, 18 Hz) instead of those which optimize the infant's response, the orientation discrimination of adults improves by a factor of 2 (0.53 deg). The results obtained from adults under optimum stimulus conditions (4 c/deg, 18 Hz) approach the estimates reported in the literature for static stimuli. PMID- 1287981 TI - Analysis of striate activity underlying the pattern onset EP of children. AB - The checkerboard onset Evoked Potential (EP) does not obtain its adult form before puberty. To determine the site of origin of these processes we studied the origin of the checkerboard onset EP in a group of 10 children between the ages of 6 and 16 years. Since the development of the waveform of the pattern onset EP varies with check size we also studied the dependence of these EPs on check size. The child checkerboard onset EPs described in this paper are dominated by a single source. Following an equivalent dipole source localization approach, the position, orientation and variation in strength of the equivalent dipole is estimated. The position and orientation of this dipole indicates an origin in the primary visual cortex (area 17). The variation in strength of the dipole changes from a single positive deflection, specific for children of 8 years and younger, into a negative-positive complex for the children studied between the age of 9 and 16 years. These changes in waveform must be due to changes in the activity pattern of the striate cortex. PMID- 1287982 TI - Pattern recognition in honeybees: multidimensional scaling reveals a city-block metric. AB - Bees were trained to discriminate ring-patterns which varied in number of rings and in size. Transfer-tests revealed size discrimination to be largely independent of pattern type and vice versa. A multidimensional scaling procedure, using Minkowski metrics as models, was applied in order to determine the bee's "perceptual metric". The city-block metric, and not the Euclidean metric, provided the best description of the data. Apparently, the bee's perceptual system derives the overall dissimilarity of complex ring-patterns additively from the component differences. These results are discussed with regard to "holistic" and "analytic" processing modes postulated for the perception of human subjects. PMID- 1287983 TI - Shape discrimination and the judgement of perfect symmetry: dissociation of shape from size. AB - We measured the accuracy with which subjects judged that a square or circle was perfectly symmetrical i.e. that aspect ratio (a/b) was exactly unity (where a and b were, respectively, the vertical and horizontal dimensions). Errors were remarkably small, ranging from 0.7 to 0.4% for the judgement of squareness and from 1.4 to < 0.1% for the judgement of circularity. Precision in judging aspect ratio was measured by requiring subjects to judge whether the aspect ratio (a/b)TEST of a test rectangle was greater or less than the aspect ratio (a/b)REF of a reference rectangle. Similar measurements were made for elliptical targets. To ensure that subjects based judgements on aspect ratio rather than a, b or (a b), the area of each successive presentation was varied randomly. The just discriminable percentage change of aspect ratio was as low as 1.6% at (a/b)REF = 1.0 (i.e. for a square or circular reference), and rose progressively as (a/b)REF was made progressively larger or smaller than 1.0. Aspect ratio discrimination threshold was independent of mean area over a sixteen-fold range of 0.25-4.0 deg2. For both rectangles and ellipses, the best value of aspect ratio discrimination threshold corresponded to a precision of encoding a and b of 14 sec arc or better. In further experiments, the method of constant stimuli was used to measure an aspect ratio aftereffect produced by adapting separately to rectangles of (a/b)ADAPT equal to 1.5, 1.0 and (1/1.5). Similar aftereffects were obtained whether the area of the test stimulus was fixed or varied randomly from trial to trial, and whether the test stimulus was rectangular or elliptical. The aftereffect could not be explained in terms of fatigue of neurons sensitive to linear dimension a or b. Nor could the aftereffect be explained in terms of the "contour repulsion" hypothesis, or in terms of orientation discrimination. We conclude (1) that the same neural mechanism determines aspect ratio discrimination threshold for rectangles and ellipses and (2) that this mechanism is sensitive to aspect ratio independently of linear dimensions. We propose that aspect ratio perception is determined by the balance of excitation of two pools of neurons that are selectively sensitive to different, but overlapping ranges of (a/b). One pool prefers aspect ratios > 1.0 and the others prefer aspect ratios < 1.0. We suppose that the two pools respond identically to changes in area (a * b).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1287984 TI - Peripheral chromatic sensitivity for flashes: a post-receptoral red-green asymmetry. AB - Thresholds of luminance and red-green chromatic flashes (200 msec) were measured on a yellow adapting field in the fovea and periphery (up to 12 degrees eccentricity for 1 degree flashes and 21 degrees eccentricity for 2 degrees flashes). Chromatic sensitivity (in cone contrast coordinates) is about 7 times higher than luminance sensitivity in the fovea but falls faster with eccentricity, so that luminance and chromatic sensitivities are similar at eccentricities of 20 degrees or less. At eccentricities greater than about 14 degrees, there is a clear asymmetry wherein green chromatic flashes are considerably less detectable than red ones. By measuring complete detection contours for many ratios of incremental and decremental red and green flashes, we isolated the red and green chromatic detection mechanisms, and demonstrated that the red-green asymmetry is not a property of the L- or M-cone response per se, but rather is a property of the post-receptoral, chromatic mechanisms. The peripheral luminance and chromatic mechanisms could be further separated with a suprathreshold luminance flash (a pedestal), since an intense pedestal masks coincident luminance test flashes but facilitates the chromatic flashes. The luminance pedestal approximately linearizes the chromatic detection function (the psychometric function). PMID- 1287985 TI - Visually induced cycloversion and cyclovergence. AB - Binocular cyclorotatory (torsional) eye movements in response to visual patterns, which oscillated sinusoidally in the frontal plane, were recorded with scleral induction coils in human subjects. Conjugate cycloversion and disjunctive cyclovergence were directly compared by in-phase and out-of-phase oscillation of the same pattern. Stimulus motion had a frequency of 0.2 Hz and amplitudes of 2-8 deg. Both response types had a similar and low gain (about 0.2 averaged over all subjects). Cycloversion showed no time lag, while cyclovergence lagged by about 600 msec. Non-fusible patterns were effective in eliciting cycloversion, but not cyclovergence. Apart from this, the nature of the pattern (randomly distributed dots, regular rows of dots, horizontal or vertical grating, Julesz stereogram or images with a pictorial significance) had only the slightest effect on the magnitude of the responses. PMID- 1287986 TI - Configural effects constrain Fourier models of pattern discrimination. AB - Many models of spatial pattern discrimination assume that judgments are based on information directly available from mechanisms tuned to limited ranges of spatial frequency and orientation. We tested the validity of this assumption for spatial frequency, orientation, and contrast information in a series of complex pattern discrimination experiments. Observers discriminated between simple gratings, between gratings masked by components that differed widely in spatial frequency and/or orientation, and between patterns that presented two cues to discrimination, one in each frequency and/or orientation band. Component cues were combined either in rigid-object correspondence (e.g. both components were rotated clockwise in one pattern and counterclockwise in the other) or in opposition (e.g. in one pattern one component was rotated clockwise, the other counterclockwise; the direction of rotation was reversed for each component in the second pattern). The results demonstrate that information from tuned pathways is not always used directly in making spatial judgments, but in some cases is combined across wide regions of the Fourier domain prior to the discrimination decision. We find two distinct patterns of combination that appear to independently signal information about texture and edges. These findings provide a potential link between low-level, spatially tuned analyzers in the visual system and higher-level pattern processing mechanisms. PMID- 1287987 TI - Segregation of mesh-derived textures evaluated by resistance to added disorder. AB - In the "figure detection task" the strength of segregation for a particular texture pair was estimated by the threshold amount of added disorder that prevented segregation of a textured figure from a textured ground. Disorder was either jitter in the orientation of the texture elements, or jitter in their xy positions, or a mixture of the two. Other procedures included lowpass filtering, and a task requiring discrimination between textured figures of different shapes. Orientation cues are weakly or inconsistently used for segregating mesh textures. The low spatial harmonics are very important. A new finding is that orientation and position jitter thresholds for a set of figure/ground texture patterns are often proportional. In a mixture the one disorder can be exchanged for the other. PMID- 1287988 TI - The influence of eccentricity on position and movement acuities as revealed by spatial scaling. AB - The rate of decline with increasing eccentricity of several position and movement acuities was measured using a method of spatial scaling. In this method all stimuli at each visual field location are simply magnified versions of each other. The influence of separation and eccentricity were dissociated by presenting stimuli on an iso-eccentric arc. For each task, the rate of decline in performance was quantified by the parameter E2 which represents the eccentricity at which stimulus size must double in order to maintain performance equivalent to that at the fovea. All tasks were found to obey the concept of spatial scaling in that performance at a given field location could be equated with performance at any other location simply by a change of scale. However, the rate at which performance deteriorated with eccentricity varied over an enormous range (over 100-fold) depending on the task itself. The advantage of such diverse peripheral gradients is clear; the goal is to establish the physiological mechanisms which underlie this phenomenon. PMID- 1287989 TI - Blurring by fixational eye movements. AB - A complete description of the loss of contrast sensitivity at high spatial frequencies requires an estimate of the role of eye movements, which could blur fine detail. We describe a new technique to isolate their effect. Observers viewed either a 100 c/deg interference fringe, which the cone mosaic aliased to a low frequency zebra stripe, or an artificial zebra stripe. The real and artificial zebra stripes have similar spatial patterns, but differ in the temporal modulation produced by eye movements. Contrast threshold was measured as a function of duration for both stimuli flashed in the dark. The ratio of the contrast thresholds for the real and artificial zebra stripes with long durations, when eye movements could have a differential effect, is always within a factor of two or so of the ratio for 1 msec flashes, when eye movements are eliminated. These results support the view that eye movements are only a minor source of image degradation even at very high spatial frequencies, and provide no support for the view that they improve high resolution tasks. PMID- 1287990 TI - Dynamic noise backgrounds facilitate target fading. AB - With strict fixation, a small uniform target of medium contrast, placed at 10 deg eccentricity, faded much faster when presented on a dynamic random noise background than on either a static random noise background or a uniform background of the same luminance. Time to first disappearance was between 10 and 16 sec when the background was dynamic, 26 sec when it was static, and 57 sec when it was uniform. Times were shortest for temporal noise frequencies of the background between 3.5 and 15 Hz. These findings are unexpected: the frequent change of pixel contrast at the edge of the target should perceptually enhance the border, make it less susceptible to local adaptation, and prevent fading. Instead, dynamic random noise facilitates, rather than suppresses fading. Three potential mechanisms are discussed: edge perturbation, jerk effect and surround induction. PMID- 1287991 TI - Color mixing in the pigeon (Columba livia) II: A psychophysical determination in the middle, short and near-UV wavelength range. AB - Pigeons were trained to discriminate between spectral lights and additive mixtures in the 350-560 nm spectral range using a successive "autoshaping" discrimination procedure [introduced in Palacios, Martinoya, Bloch & Varela, Vision Research, 30, 587-596 (1990)]. Dichromatic mixtures were found in the short and near UV region, but not in the middle-wave region. Our results suggest that color vision in the pigeon involves the active participation of five different primary mechanisms, which are differentially active in the yellow- and red-sensitive retinal fields. PMID- 1287992 TI - Red-green and yellow-blue opponent-color responses as a function of retinal eccentricity. AB - Using the hue cancellation technique, I measured the spectral sensitivities of red-green (r-g) and yellow-blue (y-b) opponent-color responses of two color normal observers at 0 (fovea), 3.3, 10, 21, and 31 degrees along the horizontal meridian of the temporal retina. The stimulus size as a function of retinal eccentricity was varied according to the cortical magnification factor. I found that the net spectral sensitivity (i.e. corrected for macular pigment) of the r-g channel was approximately constant as a function of retinal eccentricity. On the other hand, the net spectral sensitivity of the y-b channel was not constant. For the y-b channel I found a constant spectral sensitivity as a function of eccentricity when no macular correction was made. This means that the y-b system changes its yellow and blue responses with eccentricity to counterbalance the effects of macular pigment. PMID- 1287993 TI - Orientation bandwidth: the effect of spatial and temporal frequency. AB - The orientation bandwidths of psychophysically defined channels of human vision were estimated by two techniques for a wide range of spatial and temporal frequencies. The first technique was an adaptation paradigm, where the subjects' ability to see patterns of various orientations was measured before and after adapting to a high contrast pattern. The second technique evaluated subjects' ability to discriminate between two gratings of different orientations in relation to their ability to detect the patterns. Bandwidths were unaffected by temporal frequency at high spatial frequencies but increased with temporal frequency at low spatial frequencies. Bandwidths increased modestly with decreasing spatial frequency at low temporal frequencies but more drastically at high temporal frequencies. Both techniques gave similar results except for patterns with very low spatial and high temporal frequencies. In this region the stimulus appears "spatial-frequency doubled" which may be used as a cue for the orientation discrimination task. PMID- 1287994 TI - Losses of flicker sensitivity during dark adaptation: effects of test size and wavelength. AB - The losses of flicker sensitivity that occur during dark adaptation following extinction of a bleach depend greatly on the test stimuli that are used to measure those losses. Generally, the larger the test size is for a given test wavelength, the later is the loss of flicker sensitivity; for sufficiently large tests, losses become progressively more gradual. Similarly, the shorter the test wavelength is (between about 660 and 580 nm) for a given test size, the later is the loss of flicker sensitivity; for sufficiently short test wavelengths, losses become progressively more gradual. Although the pattern of flicker sensitivity loss as a function of test size is the same both foveally and parafoveally, foveal losses occur later and/or more gradually for a given test stimulus. The results suggest that losses of flicker sensitivity occur when spectrally antagonistic response(s) to the test are no longer adequate to maintain the flicker-response to that test. The results suggest also that the adequacy of such spectral antagonism depends on the local adaptation state of the retina, which becomes increasingly more light-adapted with increasingly large test size. PMID- 1287995 TI - Binocular measurements of chromatic adaptation. AB - In this paper we present asymmetric matching data that were obtained with a binocular presentation method. Our main motivation was the question whether chromatic adaptation, one of the important mechanisms that contribute to colour constancy, has evolved towards a better performance in the range of colours that are present in the natural image. For the eye adapted to a bluish illuminant for example the presence of an object with a deep yellow colour is very unlikely. So, it was expected that the colour difference between adapting light and target has an influence on the extent of chromatic adaptation. It was found that the colour shift in the observers' matches that can be attributed to chromatic adaptation indeed has a maximum. The location of the maximum, however, was unexpected, i.e. colour differences between target and adapting light that lie around 0.05 u'v' chromaticity units. Additionally, several models for chromatic adaptation were fitted to our data. It was found that, except for the simple von Kries model, Retinex Theory and difference contrast, a number of models gave good predictions for the L-wave and M-wave fundamental systems, but that predictions for the S wave system were less accurate. PMID- 1287996 TI - Probability summation of acuity in the human infant. AB - Raw data from two studies of monocular and binocular acuity development were used to determine whether a binocular acuity advantage as a function of age is predicted by probability summation and whether these predictions accurately describe the course of binocular acuity development. Two decision rules for the combination of the outputs of right eye and left eye "channels" were evaluated, the decision-threshold rule and the integration rule. Both decision rules predicted a binocular acuity advantage for infants and children aged 0-60 months. However, both rules failed to adequately describe the normal course of monocular and binocular acuity development. No binocular acuity advantage was found prior to 6 months of age while, after 6 months of age, binocular acuity was superior to monocular acuity by 0.12 log unit (0.4 octave). The absence of binocular acuity superiority prior to 6 months of age is consistent with suggestions by other authors that the immature human visual system combines information from the two eyes nonselectively. PMID- 1287997 TI - Vitamin A2-based visual pigments in fully terrestrial vertebrates. AB - As part of a broad study of the ocular and extraocular photoreceptors of reptiles, we have used high performance liquid chromatography (HPLC) to identify the retinoids present in whole eye extracts of the arboreal lizard Anolis carolinensis and the non-arboreal ruin lizard Podarcis sicula. Unexpectedly, only vitamin A2-derived chromophore was detected in Anolis, while a mixture of vitamin A1- and vitamin A2-derived chromophores was detected in Podarcis. These are the first examples of fully terrestrial vertebrates using vitamin A2-derived chromophore for visual pigment generation. Furthermore, microspectrophotometric (MSP) data for Anolis show a class of photoreceptor having a visual pigment with maximum absorbance at about 625 nm, some 40 nm further into the red than has been found in any terrestrial vertebrate examined to date. PMID- 1287998 TI - The rod-cone shift and its effect on ganglion cells in the cat's retina. AB - We examined how several characteristics of cat retinal ganglion cells--receptive field size, spatial resolution, and centre-surround antagonism--change with background illumination. Spectral sensitivity was also measured to see how these changes depend on the rod-cone shift. The radius of the centre mechanism changed very little across the mesopic range. The absence of a change can be attributed to the connections rods make with cones, and to the small spatial spread of rods which connect to a cone. The highest spatial frequency to which a cell could respond dropped sharply with falling background illumination. This loss of spatial resolution is due partly to increasing receptive field size, and partly to loss of contrast gain. Centre-surround antagonism approached zero as background illumination fell. The loss of antagonism could have been due to either a change in the subtractive relationship between centre and surround, or due to a loss of surround strength relative to centre strength; the latter was shown to be the case. PMID- 1287999 TI - Effects of sodium iodate on the electroretinogram c-wave in the cat. AB - The c-wave of the vitreal electroretinogram decreased in amplitude and was replaced by a slow, polarity reversed potential following an i.v. infusion of sodium iodate, as first described by Noell. Intraretinal recordings showed that the negative-going c-wave, induced by iodate (30 mg/kg), was composed of reduced slow pIII and trans-epithelial c-wave. The effects of iodate on these components may originate from direct effects on the retinal pigment epithelial cells, namely, a large decrease in the trans-epithelial resistance. Other factors could have contributed to the change in the c-wave amplitude. PMID- 1288000 TI - Head orientation in pigeons during landing flight. AB - Landing flights of pigeons were video recorded or filmed, and frame-by-frame measurements were made of the angle of the head relative to the horizontal, and of the position of the perch in the visual field. The angle of the head increases above that seen in free flight, to a value which is correlated with the trajectory of approach to the perch. As a result, the perch is fixated 20-25 degrees above the beak early in landing flight. The possible significance of the behaviour is discussed in relation to specialised retinal areas and to lower field myopia. PMID- 1288001 TI - "Weber's law" for position: the role of spatial frequency and contrast. AB - We used Gabor bars to measure the effects of spatial bandwidth, spatial scale, contrast and separation on three-line spatial interval discrimination (bisection). In the first experiment, we used stimuli that were well above threshold. Our results show that at all spatial scales, spatial interval discrimination (three-line bisection) thresholds are proportional to the separation of the Gabor patches (i.e. Weber's law) when the separation exceeds approximately 2.5 times the standard deviation (sigma) of the Gaussian envelope. The optimal threshold occurs when the separation is approx. 2-2.5 sigma, and for separations larger than the optimal, bisection thresholds are equal to a more or less constant Weber fraction (delta s/s) of approx. 0.02-0.04. These results are consistent with a number of previous studies. In the second experiment, we examined the effect of contrast. Our results show an interaction between separation and stimulus visibility. Reducing the stimulus contrast has a marked effect on spatial interval thresholds at small separations (e.g. separations less than about 3 sigma), and much less effect at larger separations. Thus, the Weber's law relationship appears to depend on the visibility of the stimuli, but does not depend on the spatial frequency or bandwidth of the stimuli. These results can be predicted by an ideal observer model of spatial interval discrimination. PMID- 1288002 TI - No aliasing at edges in normal viewing. AB - Although spatial aliasing by the extrafoveal retina can occur under natural viewing conditions, it does not commonly disturb our vision. One possible explanation for this is that real scenes do not have sufficient power in the high frequencies to produce aliasing. We examined whether aliasing distorted the appearance of a high contrast edge, which is a common stimulus in the environment. Observers made a two-interval forced-choice discrimination between low-pass filtered and unfiltered edges at 0, 10, 20, and 40 deg eccentricity. This discrimination could be made only when frequency components were removed below both the cone and ganglion cell Nyquist frequencies at each eccentricity. Since supra-Nyquist frequency components could not be detected in edges, they are incapable of producing aliasing. PMID- 1288003 TI - The remarkable saccades of asymmetrical vergence. AB - The saccades that usually arise near the onset of asymmetrical changes in vergence, when one eye is aligned with both targets, are remarkably different from ordinary saccades: (1) the excursions of the two eyes are typically very unequal, often differing by several fold from each other; (2) mean excursion (version) is extremely variable across replicate tests with identical targets; (3) at the end of the saccades, eye orientation is usually not even briefly stable: the aligned eye immediately reverses its movement, indicating that the pulse in muscular forces is apparently not followed by a corresponding step; and (4) a second saccade in the opposite direction can immediately follow the initial saccade of asymmetrical divergence, with no sign of refractoriness. These phenomena suggest that the pulse and step components of saccadic motoneuron activity may be generated by largely independent processes; that the step component for each eye depends only on that eye's visual input; and that the pulse components generated for each eye depend on weighted averaging of visual stimuli that impinge on both eyes. This interpretation is incompatible with most current models of saccade generation, but was anticipated in its essentials by Ditchburn [(1973) Eye movements and visual perception. Oxford: Clarendon Press]. A corollary of this hypothesis is that disparity-evoked vergence changes can be viewed as the general-case output from that system which produces fully conjugate saccades as a special case. PMID- 1288004 TI - Simple-pooling of unidirectional motion predicts speed discrimination for looming stimuli. AB - Looming objects comprise many 2D unidirectional motion elements changing over time. However, observers assign a single 3D speed to looming objects, not many independent unidirectional speeds to different regions of the object. These experiments examined speed discrimination for looming stimuli to illuminate the mechanisms underlying the perception of 3D motion. Speed discrimination thresholds for looming displays were comparable to those of fronto-parallel translating and rotating displays (approximately 5%), and thresholds were predicted from the simple linear combination of 2D unidirectional thresholds. These results suggest that 2D unidirectional motion and looming motion are not independent: the simple pooling of unidirectional motion units limits sensitivity to looming stimuli. These results do not support the notion that the visual system directly encodes relative motion within a distinct channel. PMID- 1288005 TI - Visual acuity in the horse. AB - We assessed the ease with which horses could learn visual discriminations and measured their resolution acuity. We trained three horses to press their noses against one of two large wooden panels to receive a small food reward. Following training on a series of two-choice discrimination tasks, resolution acuity was measured. Although there was some variability between animals, the best acuity obtained was 23.3 c deg-1. Within the margin of error imposed by limited anatomical data, the obtained values are consistent with predictions based on retinal ganglion cell density estimates and posterior nodal distance/axial length ratios. They suggest that the resolution acuity of the horse is limited by ganglion cell density in the temporal portion of the narrow visual streak. PMID- 1288006 TI - Separation discrimination with embedded targets. AB - Previous research has shown that separation discrimination thresholds are independent of the internal spatial scale (local spatial frequency) of the targets whose separation is being judged. The experiments reported here tested the generality of this conclusion for separation discrimination of targets that were embedded in an array of identical objects, where crowding could enhance the importance of the scale at which the individual target locations are encoded. No effect of the local spatial scale of the targets was found under these conditions. PMID- 1288007 TI - Thyroxine induces a precocial loss of ultraviolet photosensitivity in rainbow trout (Oncorhynchus mykiss, Teleostei). AB - Small (< 30 g) juvenile rainbow trout (Oncorhynchus mykiss) possess retinal photoreceptor mechanisms sensitive to ultraviolet (UV), short (S), middle (M) and long (L) wavelengths. During normal development, the sensitivity peak of the UV cone mechanism (360 nm) shifts towards the S-wavelengths (to an intermediate lambda max of 390 nm) until, at approx. 60 g, individuals are no longer sensitive in the UV (only a S-wavelength peak at 430 nm remains). This shift in spectral sensitivity is associated with the loss of small accessory corner cones from the retinal photoreceptor cell mosaic. Treating small (< 30 g) rainbow trout with thyroid hormone induced a precocial loss of UV photosensitivity and an associated change in the retinal photoreceptor cell mosaic, identical to the events that occur during normal development. PMID- 1288008 TI - Visual processing of optic acceleration. AB - We present data on the human sensitivity to optic acceleration, i.e. temporal modulations of the speed and direction of moving objects. Modulation thresholds are measured as a function of modulation frequency and speed for different periodical velocity vector modulation functions using a localized target. Evidence is presented that human detection of velocity vector modulations is not directly based on the acceleration signal (the temporal derivative of the velocity vector modulation). Instead, modulation detection is accurately described by a two-stage model: a low-pass temporal filter transformation of the true velocity vector modulation followed by a variance detection stage. A functional description of the first stage is a second order low-pass temporal filter having a characteristic time constant of 40 msec. In effect, the temporal low-pass filter is an integration of the velocity vector modulation within a temporal window of 100-140 msec. A non-trivial link of this low-pass filter stage to the temporal characteristics of standard motion detection mechanisms will be discussed. Velocity vector modulations are detected in the second-stage, whenever the variance of the filtered velocity vector exceeds a certain threshold variance in either the speed or direction dimension. The threshold standard deviations for this variance detection stage are estimated to be 17% for speed modulations and 9% for motion direction modulations. PMID- 1288009 TI - Two separate neural mechanisms of brightness induction. AB - A particular rate of quantal absorption by photoreceptors may result in a dim or an intense percept, depending on light stimulating other parts of the retina. The brightness of an object in a natural scene, therefore, depends on the amount of light reflected from the object in comparison to light from other parts of the scene. We show this phenomenon is mediated by two separate neural mechanisms at distinct levels of the visual system. The first mechanism depends on retinal image contrast between adjacent regions. The second mechanism depends on the binocularly fused "cyclopian" representation and is influenced by more remote, noncontiguous areas of the visual field. PMID- 1288010 TI - Temporal and spatial integration in dynamic random-dot stimuli. AB - Random-dot cinematograms comprising many different, spatially intermingled local motion vectors can produce a percept of global coherent motion in a single direction. Thresholds for discriminating the direction of global motion were measured under various conditions. Discrimination thresholds increased with the width of the distribution of directions in the cinematogram. Thresholds decreased as the duration of area of the cinematogram increased. Temporal integration for global direction discrimination extends over about 465 msec (9.3 frames) while the spatial integration limit is at least as large as 63 deg2 (circular aperture diameter = 9 deg). The large spatial integration area is consistent with the physiology of higher visual areas such as MT and MST. PMID- 1288011 TI - Monochromatism determined at a long-wavelength/middle-wavelength cone antagonistic locus. AB - The foveal increment threshold spectral sensitivity function for a 500 msec raised cosine stimulus without spatial edges exhibits a sharp drop or "notch" in sensitivity that coincides with the wavelength of a long-wavelength adapting field. An appropriate name for this phenomenon is the "Sloan notch", after Louise Sloan, who first observed a notch in a foveal threshold spectrum. We have examined suprathreshold discriminability on both sides of the Sloan notch produced by a 6700 td, 578 nm adapting field. In a temporal two-alternative forced-choice paradigm, a suprathreshold 650 nm low-frequency "standard" stimulus was paired with low-frequency "test" stimuli, of wavelength between 600 and 670 nm and varied intensity; the observer's task was to identify the interval containing the standard. Discriminability of the test and standard typically dropped to chance for some particular test intensity, producing "indiscriminability action spectra", up to 0.7 log units above threshold. Truncated spectra (between about 530 and 560 nm) were also obtained from observers on the middle wavelength side of the Sloan notch, for a 550 nm standard. The indiscriminability action spectra of each observer were identical, up to scaling, with the observer's threshold action spectrum. Analysis of the action spectra shows that the indiscriminable stimuli are rendered equivalent at the input to a neural pathway where L- and M-cone signals converge with opposite sign. We also investigated discriminability in the spectral region containing and immediately surrounding the Sloan notch. Suprathreshold stimuli in the spectral region near the notch produce percepts that are always discriminable from 650 and 550 nm standards (and from one another), and thus we conclude that in this spectral region, perception is mediated in part by a pathway distinct from that which signals the standards. The action spectrum of this latter pathway was estimated with a variant of the discrimination procedure, and found similar to V lambda over the spectral region 575-610 nm. PMID- 1288012 TI - Reversal in the sequence of the Benham colours with a change in the wavelength of illumination. AB - A Benham disk was rotated at 7 c/sec and illuminated by monochromatic lights from the range 534-586 nm. The elicited colours of the rings were described either with a colour naming procedure or by matching with a Munsell chip. Exchanges of hues between the two extreme rings and between the two inner rings were reported around 557 and 566 nm by the colour naming procedure, thus resulting in a hue reversal in the spatial display of colours. Similar hue shifts were also reported with the matching procedure. The effect of a possible displacement in the equilibrium of colour-opponent cell population, resulting from chromatic adaptation, is discussed. PMID- 1288013 TI - Methodology-specific Rayleigh-match distributions. PMID- 1288014 TI - Motion thresholds of briefly visible stimuli increase asymmetrically with age. AB - During a pursuit eye movement made across a stationary stimulus, that stimulus is often perceived as moving slightly in the direction opposite to the eyes (Filehne illusion). The illusion is generally thought to increase in strength when the stimulus is made visible only briefly. In two experiments the illusion was indeed observed with young subjects. However, with older subjects brief stimulus presentations yielded a strong inverted Filehne illusion (the stimulus appeared to move in the same direction as the eyes). This age dependency of the Filehne illusion is caused by an increase of only the threshold for stimulus motion in the direction opposite to the eyes. No such effect happens with the threshold for stimulus motion in the same direction as the eyes. These findings can be explained if we assume that with increasing age it takes more time to properly register retinal image velocity within the perceptual system. PMID- 1288015 TI - Orientation dependence in the recognition of familiar and novel views of three dimensional objects. AB - We report four experiments that investigated the representation of novel three dimensional (3D) objects by the human visual system. In the first experiment, canonical views were demonstrated for novel objects seen equally often from all test viewpoints. The next two experiments showed that the canonical views persisted under repeated testing, and in the presence of a variety of depth cues, including binocular stereo. The fourth experiment probed the ability of subjects to generalize recognition to unfamiliar views of objects previously seen at a limited range of attitudes. Both mono and stereo conditions yielded the same increase in the error rate with misorientation relative to the training attitude. Taken together, these results support the notion that 3D objects are represented by multiple specific views, possibly augmented by partial viewer-centered 3D information. PMID- 1288016 TI - Fabrication of a crown supporting an existing RPD using a direct-indirect technique and a dental surveyor. PMID- 1288017 TI - [Mechanisms of immune homeostasis: implications for the pathogenesis of autoimmune diseases]. PMID- 1288018 TI - [The coronary sinus as a source of activated T-lymphocytes in patients after orthotopic heart transplantation]. AB - Mononuclear cells are the component of blood responsible for allograft recognition, rejection and acceptance. Shifts in the patterns of various mononuclear cell subpopulations were often used as a diagnostic tool in detection of heart rejection. The specificity of mononuclear cell monitoring has remained a controversial point until today, because infections led to similar changes as organ rejection. In this study we investigated whether mononuclear cells taken from coronary sinus blood give more information about the immunological status of the transplanted heart than those taken from central verous blood. After endomyocardial biopsy, coronary sinus blood was sampled by catheterization under X-ray control. Blood from the right atrium was taken for control measurement. Mononuclear cells obtained by density gradient cytocentrifugation were stained with monoclonal fluorescein conjugated antibodies detecting CD4- (T helper)-, CD8 (T suppressor)-, CD25- (Interleukin-2 receptor), and the CD71- (Transferrin receptor) antigens. Endomyocardial biopsies were graded according to the Billingham scheme. In the absence of rejection, the phenotypes of mononuclear cells from the coronary sinus did not differ from those of right atrial cells. Mild rejection led to a statistically insignificant increase of CD4- CD25- and CD7-antigen bearing cells in the coronary sinus blood, whereas the CD8 positive cells remained stable as compared to mononuclear cells from the right atrium. However, patients with moderate rejection showed a significant elevation of CD4 positive cells and activated T-cells (CD15-, CD71-positive cells) in the coronary sinus as compared with cells from the right atrium. The T helper/suppressor ratio (Th/s-ratio) shifted towards the T-helper population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288020 TI - [Alarm plan BLUE--a concept for managing mass emergencies in emergency ambulatory care of the new Vienna general hospital]. PMID- 1288019 TI - [Differential diagnosis of ascites and abscess forming hepatitis in AIDS patients with reference to the first patient with microsporidia infection in Austria]. AB - We report on a 30 years-old female AIDS patient suffering from generalized pneumocystosis and intestinal microsporidiosis. The chest X-ray showed a right sided pleural effusion; the lungs showed no areas of consolidation and the heart and the vessels were normal in size. Sonography revealed multiple cystic lesions of the liver measuring 1-3 cm in diameter, as well as ascites. Pneumocystis carinii was detected on cytological examination of the bronchoalveolar lavage fluid, the pleural effusion and the ascitic fluid. Intestinal microsporidiosis was diagnosed by cytological examination of the stool. Both pneumocystis carinii infection and microsporidiosis may cause hepatitis and ascites. In our patient the organ manifestations of the two infections did not overlap. Since simultaneous organ manifestations are possible the differential diagnosis is discussed. This is the first case of microsporidiosis reported in Austria. PMID- 1288021 TI - ["Utstein style" documentation of resuscitation--initial experiences]. PMID- 1288022 TI - [Risk of HIV infection in the area of emergency medicine]. PMID- 1288023 TI - [Emergency admission to the general hospital in Vienna--the first annual report]. PMID- 1288025 TI - For whom the bell tolls. PMID- 1288024 TI - [Incidence of acute mountain sickness at intermediate altitude in the Austrian alps]. PMID- 1288026 TI - [Lymph drainage with secondary lymphedema caused by Kaposi sarcoma]. AB - For reasons not yet known HIV infected patients in the final state of their aids disease often tend to develop Kaposi's sarcoma. These tumours result in secondary lymphatic edema which is found on both sides of the sarcoma up to the regional lymphatic nodes, transferred by the tumour cells. Depending on the state of the edema, a lymph drainage treatment is indicated palliatively; the patients can thus be relieved. A fundamental deterioration of the prognosis is not to be expected, the more as all patients are in the final state of this not yet curable disease. Differing from treatment of other lymphatic edema, it is of special importance to the therapist--apart from the difficult and specifically psychic burden--to pay attention to a protection from infection by gloves as a precaution for each single treatment. PMID- 1288027 TI - [Neurologic principles of edema in inactivity]. AB - The complete immobilisation of a limb alone can lead to the formation of oedema. Whereas the oedema secondary to inactivity induced by immobilisation is completely reversible, and will only lead to tissue damage in the longterm, neglect of oedema secondary to inactivity in the presence of central and peripheral paresis (apoplectic insult, paraplegia, damage to the plexus brachialis) may entail serious consequences due to the danger of tissue fibrosis. With paresis of an extremity, the lymphovenous return is impaired by two decisive factors: increased hydrostatic pressure in the distal limb segment, and absence of the muscle pump. In flaccid paresis, where there is low muscle tone and no muscle pump action, there is also a low venous tone and the resultant hydrostatic pressure is especially high. Venous stasis in the sub- and prefascial veins leads to increased protein loss from the venous limb of the capillaries and the venules. Compensation initially occurs in the prefascial lymph outflow region (latent oedema) which becomes decompensated if overloaded (visible oedema). Fibrosis of the subcutis and trophic skin changes are the result. In spastic paresis the regional subfascial lymphatic system responds with lymphangiospasm. Where the sympathetic innervation is interrupted (e.g. brachial plexus paralysis) there is passive hyperaemia of the terminal vessels with vascular dilatation and lymphangioparalysis. Insufficiency of the vascular walls results in an accumulation of protein in the tissues, which ultimately ends in fibrosis with ankylosis and shortening of the tendons and muscles. The early administration of complex physical decongestion therapy with manual lymphatic drainage can prevent this state. PMID- 1288028 TI - [Contribution of prelymphatic structures to lymph drainage]. AB - Vitalmicroscopic findings confirm the existence of a "low resistance pathway" for the transinterstitial fluid movement from the pillaries to the initial lymphatics. One part of this prelymphatic system is represented by submicroscopical spaces along the connective tissue fibres between ground substance (high resistance pathway) and fibre surface. The other part is represented by a network of prelymphatic tissue channels which are open connected with the initial lymphatic system. PMID- 1288029 TI - [The tomb monuments of the Dukes of Brabant (12th-14th century)]. AB - Godfrey with the Beard, Count of Louvain, acquired in 1106 the title of "Duke of Lower-Lorraine", together with the possession of the large margraviate of Antwerp. Ever since 1188, the title: "Duke of Brabant" became usual and the name "Brabant" stood for the whole of the Duke's territories. Duke John I completed the expansion-policy of his predecessors by annexing the Duchy of Limburg after the battle of Woeringen (1288). In 1430, Brabant was merged into the large Burgundian Duchy of Philip the Good. The tombs of the Dukes of Brabant were not concentrated in one dynastic necropolis, but located as well in abbeys (Affligem and Villers-la-Ville) as in churches belonging to cloisters or chapters, in Louvain and Brussels, the two towns successively used as the ducal residence. The Dukes were always buried in the most privileged part of the church, namely, the choir. Their remembrance was perpetuated by the building of a mausoleum on which the lying image of the decreased ("le gisant") was chiselled. Most mausolea did not escape damaging or even complete destruction. The following mausolea are reviewed: The tomb of Henry I (1235) in the St.-Peter's church at Louvain; it is erected in dark blue limestone from Tournai and was at first decorated with gilt. The tomb of Mathilde of Boulogne and Mary of Brabant (ca. 1260) in the St. Peter's church at Louvain, also in dark blue limestone from Tournai, and at first, polychrome. The tomb of Henry II (1248) in the abbeychurch of Villers-la Ville, nowadays disappeared. The tomb of Godfrey I (1139), in the abbeychurch of Affligem, probably built at the end of the 13th century and nowadays disappeared. Recently the "Service des Fouilles" of the Brussels University has been excavating on the site of the former Franciscan church in Brussels and discovered the foundations of the burial vault of John I. PMID- 1288030 TI - [Identification of the first Duchess of Brabant. Anatomo-historical study]. AB - After World War I, the St. Peter's church at Louvain had to be restored. When the floor of the choir was broken up, a vaulted tomb house, containing a heap of bones, was discovered. The study of the historical past of the church building was committed to Leo Van der Essen, Professor of History at the Louvain university, while Charles Nelis, Professor of Anatomy at the same university, was charged to identify, as far as possible, the discovered bones. Prof. Nelis succeeded in rebuilding three skeletons with bones that fitted together. He chiefly discovered on these skeletons a number of osteological variants, which in fact are known as being very rare; but their frequent existence on the three skeletons and their absence on the other bones, pointed towards an hereditary factor and the kinship of the three persons. By combining Prof. Van der Essen's historical data with his own heredomorphological findings, Prof. Nelis identified in the year 1930 the Dukes of Brabant from the twelfth and the thirteenth centuries, namely Godfrey II, Godfrey III and Henry I (father, son and grandson). With the help of the medical historian Dr. Tricot-Royer, Prof. Nelis extended his investigation to other members of the dukes' family, namely Saint Albert, Prince bishop of Liege and brother of Henry I, whose shrine was preserved in Mechlin, and Henry II, son of Henry I, whose tomb was located in the ruins of the abbey of Villers-la-Ville. By measuring and digging in the gardens of the Affligem-abbey, according to historical documents, Dr. Tricot-Royer could find the graves and the skeletons of the first Duke Godfrey I with the Beard, of his daughter Queen Alice and of Godfrey of Gaesbeeck, brother of Henry II. Thanks to the unusual frequency of the same hereditary traits, the kinship with the first three skeletons was established and the historical indications could be confirmed by the anatomical science. The heredo-morphological pioneer research of Prof. Nelis on eight personages from five generations of the same family is unique. PMID- 1288031 TI - [Revision of the Kaufman Assessment Battery for Children for German speaking regions. Part 2: Areas of application and criteria of reliability]. AB - Adaptation, structure and standardization of the German version of the K-ABC, a test of intelligence and achievement in children comprising 16 subtests, were discussed in the first part of this article. Part 2 deals with aspects of test administration intended to make the procedure simple, objective and appealing to children. Also discussed are possibilities for internal and external comparison of test scores, approaches to interpretation and ideas for remedial measures that are an integrated feature of the K-ABC concept. Assessment of numerous psychometric properties of the K-ABC demonstrated the reliability and validity of this test. PMID- 1288032 TI - [Prevalence and follow-up of psychiatric disorders in childhood and adolescence. Results of a prospective epidemiologic longitudinal study from ages 8-18 years]. AB - In a prospective longitudinal epidemiological study with assessments at age 8, 13 and 18 the prevalence rate for psychiatric disorders remained constant at about 16%. The sex ratio for severe disorders was male dominated even in adolescence, which was a consequence of the high rate of unsocialized disturbances of conduct in boys. Persistence of psychiatric disorders between age 13 and 18 was about 50%, as had previously been the case between age 8 and 13. One child in four suffered from a psychiatric disorder for at least 10 years. In childhood, conduct disorders had a very poor prognosis and emotional disorders a very good one. In adolescence, the course of disorders depended on an interaction between diagnosis and gender. Boys with unsocialized disturbances and girls with emotional problems had a poor prognosis. PMID- 1288033 TI - [Illness concepts of children. Validation of a modified locus of control test in illness and health]. AB - We investigated the health and illness concepts of 53 healthy children aged 8 to 14 years using a modified illness and health locus of control scale (KKG, Lohaus and Schmitt, 1989) with the scales internal, external-p (powerful others) and external-c (chance). A comparison of the results with those on self-esteem (FSK 4 6), anxiety (CMAS-R) and hopelessness (HSC) scales showed a decrease in externality, but not an increase in internality, with increasing age and a correlation between self-confidence and a more internal locus of control. The influence of children's health locus of control on treatment compliance is discussed. PMID- 1288034 TI - [Long-term course of dyslexia beyond the school years: catamnesis from pediatric psychiatric ambulatory care]. AB - In our follow-up study 12 years after index admission we were able to examine 59 out of 115 male patients who had been diagnosed in our department as dyslexic (mean age: 10.1 years). Spelling skills at follow-up were more than one standard deviation below the norm for the subjects' age (T-value on the RT of only 24). About half of our patients had participated in a specific spelling remediation program lasting more than 6 months, but at follow-up no effect of therapy could be demonstrated. The patients with the higher IQs regressed in spelling less than those with the lower IQs. We assume that the effects of remediation programs do not survive therapy and school for long because later on good spelling is no longer either required or encouraged. Our patients were severely impaired in their school career: Although their average IQ was 112 only 6 out of 59 had completed a college-preparatory program (Abitur), all of them from middle-class families with well-educated parents. Our patients chose occupations corresponding to the type of high school diploma they had, often those requiring practical skills rather than reading or spelling skills. Patients who had completed no more than the nine obligatory years at school were less content with their work than expected. Emotional disorders during the past 6 months were no more frequent than expected. In a self-report about delinquency there was no difference compared to a random sample. PMID- 1288035 TI - [Differences in the classification of psychiatric and child psychiatric disorders with ICD-10 and DSM-III-R]. PMID- 1288036 TI - [The psychiatric status of Jewish adolescents in Germany]. PMID- 1288037 TI - [Child guidance services provided by the Child and Adolescent Guidance Law from the child and adolescent psychiatric viewpoint]. PMID- 1288038 TI - Skin disease and malignancy. An epidemiological study. AB - The aim of this work was to develop a computer program (CANEST) to estimate the risk of cancer in patient populations and to use this program to investigate cancer risk associated with several dermatological disorders. Patients seen at the dermatology departments at the Karolinska Hospital and South Hospital were used for the study of chronic urticaria, condylomata acuminata, basal cell carcinoma, lichen planus and positive patch tests. The national Swedish In Patient Register was used to find all patients hospitalized for dermatomyositis or polymyositis since 1964. From eleven large dermatological centers in Sweden, details of close to 5,000 PUVA-treated patients were obtained for study. The computer program CANEST was developed and used to calculate the expected number of malignant tumors in these patient populations, based on incidence data from the Swedish Cancer Register for the years 1958-1987. By matching the patients' records with the Cancer Register the actual number of cancers was obtained. Of 1,155 patients with chronic urticaria, a malignancy was diagnosed in 36, while the expected number was 41: clearly there is therefore no association between chronic urticaria and malignancy. In 3,260 patients with condylomata acuminata there was no increased risk of cancer in situ of the cervix (relative risk = 1.5; 95% confidence interval 0.9 to 2.5) and the number of genitourinary cancers in males was almost three times higher than expected (2.6; 1.2 to 5.0). These results indicate that the risk of developing cervical carcinoma in situ is less than previously thought, but the implications of the increase in genitourinary tumors in males are uncertain. Patients with basal cell carcinoma had an increased risk of malignancy in general. Melanoma risk was seven times greater in males (6.6; 3.0 to 12.5) after the basal cell carcinoma diagnosis. Risks of squamous cell carcinoma of the skin, lung cancer, thyroid cancer and cancer of the uterine cervix were also increased. No increased risk of cutaneous malignancy was found in 2,071 patients with lichen planus, but for oral cancer it was six times greater in males (5.9; 2.5 to 11.4). A slight general increase in malignancy risk was found in 2,183 males (1.3; 1.1 to 1.5) with positive patch tests, but not in 3,675 females. When individual sites were analyzed, cancers of the lung, larynx, uterine cervix and prostate were significantly increased. The implications of this are uncertain, but might indicate a common failure of the immune system which might predispose for both conditions, or be a marker of certain occupational exposure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1288039 TI - Cement eczema. An epidemiological intervention study. PMID- 1288040 TI - [Digestive lesions related to N.S.A.I.D. (epidemiology and prevention)]. AB - The frequency of gastrointestinal ulcers and ulcers complications induced by non steroidal anti inflammatory drugs (NSAID) increases continuously. This is a major health problem, since 1.5% of general population (mostly elderly people) take regularly NSAID'S. NSAID'S gastropathy is asymptomatic in nearly 50% of cases, even in case of big gastric ulcer. A severe hemorrhage or a gastric perforation can occurred in the absence of previous symptoms. When the patient had epigastric symptoms during a treatment with NSAID'S, upper GI endoscopy is normal in 50% of cases. NSAID'S are ulcerogenic by decreasing the capacity of the gastric mucosa to produce prostaglandin (PG) and by weakening gastric mucosal barrier. H2 blockers are not effective to prevent such lesions. Elderly women, are at high risk of gastric mucosal lesions and complications. In a prospective study, it was shown that misoprostol was effective to reduce the rate of NSAID'S induced gastric and duodenal ulcers. Up to date, epidemiologic studies don't show any population group at no risk of NSAID'S induced gastric lesions. The actual problem, now, is to determine which groups of patients are at high risk of complication in order to clarify the indications of preventive treatment. Today, in France, it's believed that old patients, with organic pathology (respiratory, cardiac, hepatic or urinary) and/or using two or more NSAID'S are at high risk. PMID- 1288041 TI - Recent progress in cholera vaccination. AB - Cholera disease remains an important cause of morbidity and mortality in the third world. The parenteral cholera vaccine actually used offers only a 50% protection during 6 months. As Vibrio cholerae and its toxin don't cross the gut wall, the aim of new vaccines is to prevent the colonization and growth of the vibrio in the jejuno-ileum and to inhibit the fixation of cholera toxin (CT) on its enterocyte membrane receptor. This can be afforded by stimulation of the gut local immune system mainly represented by secretory IgA antibodies (Abs). New vaccines should comprise both bacterial and CT antigens and must be given by the oral route to induce the production of specific secretory IgA Abs in the gut. Four different ways are actually under study to produce an oral cholera vaccine. 1. Combination of CT-B subunit and killed vibrios. 2. Live recombinant Vibrio cholerae in which the CT coding gene has been deleted. 3. Synthetic peptides reproducing some immunodominant CT-epitopes. 4. Manipulation of the idiotypic network to induce the production of Abs mimicking CT-epitopes. This paper reviews the actual developments and advantages of these four approaches. PMID- 1288042 TI - [Oxygen metabolism and toxicity in the phenomenon of ischemia-reperfusion]. AB - One of the major cause of human disease results from the compromise of blood flow and oxygen delivery to tissues. Ischemia phenomenon is defined as blood flow that is inadequate to maintain normal tissue function. Prolonged ischemia ultimately results in irreversible changes in cell metabolism and cell death. Historically, it was felt that if ischemia results in altered cell function and injury, then reoxygenation or reperfusion leading to a restoration of a normal blood flow was expected to have a beneficial effect and promote salvage of tissue depending on the extent of ischemia. Recent studies have, however, revealed that reoxygenation leads to an oxygen metabolism resulting in the generation of active and toxic oxygen intermediates (free radicals) which play an important role in the pathophysiology of reperfusion injury. PMID- 1288043 TI - Immune mechanisms in alcoholic liver disease. AB - This paper reviews the potential role of immune factors in alcoholic liver diseases. They can either be involved in liver damage and hepatocyte's neurons or in the development of liver fibrosis, or in the sequellae of the disease. Cytokines, as mediators of the relationships between circulating monocytes, Kupffer cells, sinusoidal cells, Ito cells and hepatocytes, seem to play a crucial role in the development of the disease. Studies are now ongoing which try to identify the alcohol-related cofactor which triggers immune activation and the development of liver damage. PMID- 1288044 TI - Beta-endorphin-immunoreactive cells in the human fetal pancreas. AB - This investigation has been carried out on 50 samples of fetal pancreata from the 10th to the 32nd week of gestation using the PAP technique. beta-Endorphin reactive cells were morphometrically recorded by means of the point-counting method. beta-Endorphin reactivity occurred for the first time during the 15th week. During further development, beta-endorphin cells were found inside and outside the islets. From the 18th to 23rd week, these cells were primarily localized in the islet periphery. From the 24th week, they rearranged and occurred in irregular positions mixed with other islet cells. This rearrangement took place with a 4 week delay compared with the basic cell types of the islet organ. The extrainsular portion of these cells in the exocrine parenchyma varied between 0.3% in the 27th week and up to 10% in the 22nd week. Concerning the adult human pancreas, it has been suggested whether beta-endorphin cells may be a 6th basic cell type of the islet organ. Previous studies on the coexistence of somatostatin, glucagon and beta-endorphin in the same islet cell and the morphometric analysis would support this assumption. Biochemical examinations indicate that beta-endorphin is a modulator of insulin, glucagon, and somatostatin secretion in the islet organ. This is supported by the fact that beta-endorphin cells have extended cell bodies which is typical of cells with paracrine function. PMID- 1288045 TI - Light and electron microscopic studies of lectin binding to the glycocalyx of rat pancreatic cells. II. Light microscopic changes after induction of an olive-oil pancreatitis. AB - Using a battery of 7 horseradish peroxidase marked lectins (WGA, RCA I, PHA, LCA, PNA, UEA I, LPA) or 2 unmarked lectins (Con A, VAA I) and HRP-marked antibodies, the binding to acinar cells with a postembedding technique on semithin sections of rat pancreatic tissue after olive-oil pancreatitis was studied light microscopically. The lectin binding of the normal healthy rat pancreatic tissue (Jonas et al. 1991) changed remarkably. Whereas the apical glycocalyx of acinar cells with the strong binding of WGA, RCA I, and PHA remained unchanged within the first 10 min of damage, the basolateral cell surface lost the typical specific binding of UEA I within the initial phase of pancreatitis just 2 min after injection of olive-oil. Con A and VAA I were found to be very reactive with the necrotic cells 60 min after administration of oil. The results were discussed in relation to the possible functions of the 2 main domains of the pancreatic acinar cell glycocalyx. PMID- 1288046 TI - Histochemical characterization of carbohydrate residues during the morphogenesis of gastrointestinal and respiratory systems of Caretta caretta. AB - The distribution of carbohydrates in the gastrointestinal and respiratory tract of Caretta caretta during embryogenesis and postnatal development was investigated by histological and histochemical techniques and using fluorescein labelled lectins. The results indicate that the compartmentalised expression of glycoconjugates found in the juvenile Caretta caretta is acquired during development. The occurrence of neutral carbohydrates in cells and extracellular matrix was dependent on the developmental stage of the animal. In general, periodic acid Schiff positive glycoconjugates of the respiratory tract occurred at an earlier stage of development than those from the gastrointestinal system. The lectin binding pattern of both organ systems revealed a more refined pattern of the types of carbohydrates present during development. Wheat germ agglutinin showed the broadest binding pattern, whereas Soy bean agglutinin and phythaemagglutinin were more limited in their binding to tissue structures. The terminal carbohydrates detected in the gastrointestinal and respiratory tract of Caretta caretta were similar to those observed in mammals; this finding emphasises the suitability of Caretta caretta as a model system for amniote development. PMID- 1288047 TI - Localization of proteins immunologically related to erythrocyte protein 4.1, spectrin and ankyrin in thyroid gland. AB - Analogues of erythrocyte protein 4.1, spectrin and ankyrin were examined in the thyroid gland of pig and rat by immunohistochemical techniques. Analysis with immunofluorescence microscopy revealed that the peripheral cytoplasm and apical lateral plasma membrane of follicle epithelial cells of thyroid glands were stained with antibodies against erythrocyte protein 4.1, spectrin, or ankyrin. The results indicate that membrane skeletal protein lattice might exist in thyroid follicle epithelial cells. PMID- 1288048 TI - Comparison of three histochemical methods for assaying lactate dehydrogenase in liver. AB - The mean activity of lactate dehydrogenase (LDH) in hepatocytes near the central vein region of unfixed sections of mouse liver was determined and compared with 3 different histochemical methods: conventional method, polyvinyl alcohol (PVA) method, and gel film method. An image analysis system was used for measuring the enzyme activity in single hepatocytes. The mean activities were approximately 1.4 and 2.7 times higher with the PVA and a gel film techniques respectively than with conventional aqueous media. The highest activity of LDH was obtained with gel media; this can be explained by the lowest diffusion late of this soluble cytoplasmic enzyme from the secretion into the medium. In the conventional technique, the apparent activity was found to be about 16% lower when sections were incubated vertically in a large volume of medium than when they were incubated horizontally in a small volume of medium. PMID- 1288049 TI - Nucleolar organizer regions in acute and chronic leukaemias. AB - A silver staining technique for nucleolar organizer regions (NORs) has been applied to bone marrow biopsies of various types of acute and chronic leukaemias. This method could be easily evaluated on resin-embedded bone marrow obtained from acute lymphocytic leukaemia (n = 12), acute myelogenous (n = 16), chronic lymphocytic (n = 16) and chronic granulocytic (n = 20) leukaemia. A significant difference (p < or = 0.1) was only found between the AgNOR numbers in nuclei of lymphocytes from acute and chronic leukaemia (mean of 1.23 to 1.40 and 1.58) and those of cells from acute and chronic myelogenous leukaemia (from a mean of 5.00 to 9.17 per nucleus). However, no significant difference was observed among cells of various types of acute and chronic myelogenous leukaemias, despite of their markedly higher staining intensity and proliferative activity. The greatest mean of AgNOR numbers was counted in monoblasts of acute myelomonocytic leukaemia. It is suggested, that higher AgNOR counts in nuclei of more malignant leukaemic cells are in parallel with their mitotic activity and could be related to their elevated cell turn-over. PMID- 1288050 TI - Effect of flumecinol (Zixoryn) on the cytochrome P450 and cytochrome P448 dependent hepatic microsomal monooxygenase activities in male rats. AB - The effect of three-day oral administration of 50 mg/kg bw. and 100 mg/kg bw. flumecinol (Zixoryn, Gedeon Richter Chemical Works Ltd., Budapest, Hungary) and intraperitoneal administration of 50 mg/kg bw. phenobarbital as well as the single intraperitoneal administration of 20 mg/kg bw. 3-methylcholanthrene on various cytochrome P450 and P448 dependent hepatic microsomal enzyme activities was studied in male albino Wistar rats. 50 mg/kg bw. flumecinol had no significant effect. 100 mg/kg bw. flumecinol had an inducing effect comparable to the one of phenobarbital. The activity of the cytochrome P448 dependent 7 ethoxyresorufin O-deethylase was enhanced by all three substances, but flumecinol's effect was by far behind that of 3-methylcholanthrene, so the carcinogenic promoter effect of flumecinol can be questioned. PMID- 1288051 TI - Possible role of bile deficiency in the development of intestinal syndrome of acute radiation disease. AB - Experimentally induced bile deficiency significantly accelerates the development of acute gastrointestinal syndrome in the irradiated rat. The usual 11 days of survival is reduced to 5 days. In view of the experimental results it seems justifiable to conclude that endotoxins play an important role in the development of this syndrome. PMID- 1288052 TI - Vascular biomechanical factors in regulation of arterial hemodynamics: computer models. PMID- 1288053 TI - Newly identified steady-state potassium channels in rat hippocampal neurons. AB - We report two new types of potassium channels in cultured hippocampal neurons of rat. Both channels occurred in the soma membrane of these cells at very low density. They were active in steady-state conditions, within a wide voltage range that included the resting membrane potential. Their open probability was enhanced by membrane depolarization, but not influenced by Ca ions. In symmetrical 150 mM KCl the channels showed a slope conductance of ca. 40 and 80 pS, respectively. Current-voltage relations of both K channels show a negative slope at high positive voltages. PMID- 1288054 TI - Impact of single neonatal allylestrenol treatment on the estrus cycle of rats treated with FSH+LH or TSH. AB - Neonatal allylestrenol treatment administered to female rats significantly increases the duration of estrus phase in the sexual cycle. Treatment with follicle stimulating hormone (FSH) + luteinizing hormone (LH) in adulthood prolongs the duration of estrus even on its own; the effect, however, is more pronounced in those animals who were treated (imprinted) with allylestrenol neonatally. When administered to the control animals, the chemically related thyreotrop hormone (TSH) is either indifferent or it even decreases the estrus index. In animals having received neonatal allylestrenol treatment, however, TSH administration increases significantly the duration of the estrus phase. Either with or without FSH+LH treatment, the ratio of estrogenic to gestagenic phase increases following neonatal allylestrenol treatment. The experiments call attention to the potential functional risks inherent in neonatal allylestrenol treatment. The actual risks, however, seem to be smaller than the effects seen at the receptor level. PMID- 1288055 TI - Hemodynamic observations following orthotopic cardiac transplantation: hemodynamic responses to upright exercise at 1 year. AB - Central hemodynamic responses during upright exercise were studied at 1 year in 40 orthotopic cardiac transplant recipients. Hemodynamic responses were characterized by slow rise in heart rate and blunted peak exercise heart rate response, a significant early increase in stroke index followed by a plateau phase, and a steady increase in ventricular filling pressures and pulmonary artery pressure. In spite of exclusive utilization of the Frank-Starling mechanism to augment cardiac output during early exercise, the pressure responses were comparable to those reported in normal subjects. Our observations also indicate that similarly to normal subjects, the heart rate response plays an important role in the cardiac output achieved at maximum exercise. Although patients with younger donor hearts achieved a more favorable maximum heart rate, the other hemodynamic parameters showed no correlation with the donor heart age. Thus, no hemodynamic disadvantage of older donor hearts could be demonstrated. These data provide further enlightenment regarding the mechanisms of the well preserved functional capacity noted in these patients. PMID- 1288056 TI - Hemodynamic observations following orthotopic cardiac transplantation: evolution of rest hemodynamics in the first year. AB - The evolution of resting hemodynamics was studied at 1 week and 1 year in 40 patients following orthotopic cardiac transplantation. Abnormal hemodynamics after transplantation, characterized by elevated ventricular filling pressures (indicating diastolic dysfunction) and also by pulmonary hypertension, showed normalization by 1 year. In the absence of innervation, the resting heart rate of heart transplant recipients should theoretically be close to the intrinsic heart rate predicted by the age of the donor heart. In this study, a high incidence of relative sinus bradycardia (an indicator of sinus node dysfunction) was noted in the first post-operative week, although again there was a tendency to normalization by 1 year. These beneficial changes help to explain the dramatic and sustained improvement in the functional capacity of these patients late after transplantation. PMID- 1288057 TI - Impact of combined hormonal pretreatment (insulin+TSH) on the imprinting of hormones administered in combination to Chinese hamster ovary cell culture. AB - Cultured Chinese hamster ovary (CHO) cells were treated (imprinted) with insulin and with thyrotropin (TSH) related to gonadotropins (FSH+LH). When one week later the treatment was repeated with one of the hormones, considerable differences could be observed in the binding capacity of the cells. In the hormone combination TSH was able to evoke persistent imprinting only to a markedly lesser degree than insulin, meanwhile the imprintatory effect of insulin was of greater extent even on the cell regarded to be unspecific for insulin. Hormone treatment of one hour duration--when investigated immediately after--did not extinct the binding capacity to TSH but enhanced that to insulin. With the deterioration of the conditions of culturing, the enhanced binding capacity disappeared. PMID- 1288058 TI - Histochemical study on adrenal delta 5-3 beta-hydroxysteroid dehydrogenase activity in cadmium treated toad (Bufo melanostictus). AB - Effect of a single subcutaneous injection of cadmium chloride at the dose of 0.5 mg/toad on adrenal delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta HSD) was observed after 7 days. The activity of delta 5-3 beta-HSD was measured histochemically. The experiments indicate that cadmium chloride resulted in a significant decrease in the activity of adrenal delta 5-3 beta-HSD in toad during breeding season (June-July). PMID- 1288059 TI - Immunoglobulin-G and creatinine levels in rabbits in altitude adaptation. AB - The changes of immunoglobulin-G and creatinine levels in mid-altitude were investigated in rabbits. The animals living at sea level were exposed to 2240 m altitude for 22 days period. When compared with sea level values; immunoglobulin G levels were significantly low. Serum creatinine level decreased significantly in the 2nd day, then reached the sea level amount on the 12th day. On the 22nd day a significant increase was observed. It was concluded that the decrease in immunoglobulin-G values may be due to the depression of protein synthesis. The increase in plasma creatinine level would be explained by the decrease in urine. PMID- 1288060 TI - Morphometric and time lapse analyses of rapid-onset neurites stimulated by cycloheximide in NG108-15 cells. AB - We previously reported that the laminin-induced outgrowth of neurites in the first 4 hr after plating ('rapid-onset neurites') is markedly stimulated by inhibitors of protein and RNA synthesis, including cycloheximide, puromycin and actinomycin D. Our original interpretation of this finding was that inhibiting protein synthesis led to metabolic changes in the cell which converged upon the intracellular pathway used by laminin to stimulate neurite formation. Alternatively, Preston et al. (1987, Proc. natn. Acad. Sci. U.S.A. 84, 5247-5251) suggested that cycloheximide acts by inhibiting neurite retraction. In order to resolve these conflicting interpretations, we decided to re-examine the effects of cycloheximide using time lapse analyses of NG108-15 cells grown on laminin, together with morphometric analyses of cultures fixed at 1.5 or 3 hr after plating. Cycloheximide was found to cause both an increase in neurite initiation within the first 1.5 hr after plating, and a decrease in the occurrence of neurite retractions between 1 and 3 hr. Investigators should be aware of the effects of biosynthetic inhibitors on neurite growth, since these agents are employed widely in studies of cultured neural cells, particularly those involving receptor metabolism and phenotypic differentiation. PMID- 1288061 TI - NCAM as a differentiation marker of postmigratory immature neurons in the developing human nervous system. AB - The regional distribution and cellular localization of the neural cell adhesion molecule were investigated in the developing nervous system of human embryos and fetuses, by using immunocytochemistry with antibodies against the human neural cell adhesion molecule. Embryos and fetuses with crown-rump lengths ranging from 15 to 80 mm (corresponding approximately to 6-12 ovulation weeks) were examined. In the telencephalon, immunoreactivity was found in the primordial plexiform layer and in the early cortical plate. During later stages, immunoreactivity was present in the marginal zone, cortical plate, developing subplate zone and radiations of the internal capsule. In the mesencephalon and rhombencephalon, neuronal perikarya were outlined and strong staining was present in fiber bundles. In the spinal cord, strong immunostaining was present in fiber tracts and in dorsal and ventral roots. Immunostaining outlined perikarya of dorsal and ventral gray columns; the neuropil of the developing gray matter was also stained. Contrary to findings in some other species, precursor cells in the proliferating zones, i.e. all cells of ventricular zones and the external granular layer in the proliferation were not stained. Reactivity, however, was also observed in single mature-looking nerve cell bodies and their processes, which were localized in proliferating zones. All peripheral nervous structures including nerve fibers and peripheral nervous tissue components derived from the neural crest (i.e. sensory and autonomic ganglia) expressed the neural cell adhesion molecule. At the cellular level staining always appeared to be associated with the entire cell membrane of a given neuron including its outgrowing processes. Immunocytochemical staining for neural cell adhesion molecule is an excellent method for the identification of single nerve fibers, nerves and nerve cell bodies in situ in the developing peripheral and early central nervous system. The neural cell adhesion molecule is suggested as a marker of postmigratory immature neurons in the developing human nervous system. PMID- 1288062 TI - Expression in murine and human neuroblastoma cell lines of VGF, a tissue specific protein. AB - Screening by different means has demonstrated the presence, in human and murine neuroblastoma cell lines, of VGF, a gene product identified in a limited number of neuronal and endocrine cells. Indirect immunofluorescence and Western and Northern blot analyses have shown the presence of this protein in some of the tested lines, confirming that VGF is not an ubiquitous molecule. Further studies, using human SK-N-BE and murine N18TG2 lines, showed that VGF expression is upregulated during differentiation, suggesting that various species, including man, express VGF and regulate it in a similar manner. The subcellular localization of the protein, which is associated with vesicles, its electrophoretic molecular profile and its specific release under different conditions are all consistent with results reported in other cells. Neuroblastomas are thus added to the class of VGF-positive cells and provide a new in vitro model for investigation of the structural and functional properties of this protein. PMID- 1288063 TI - Neuronal sprouting and synapse formation in response to injury in the mouse organ of Corti in culture. AB - The effect of mechanical injury on induction of regenerative phenomena within the neurosensory epithelium was investigated in cultures of neonatal mouse cochlea. The oldest examined culture in which new neuronal growth followed insult, was injured at 13 days in vitro and fixed 24 h later. By far, the most vigorous regenerative reaction was observed in a 3-day culture 4 h post-injury. The reaction included sprouting of nerve fibers injured directly, synapse formation between the surviving hair cells and sprouting neuronal growth cones, wrapping of growing nerve fibers by extending processes of hair cell cytoplasm, and collateral sprouting of synaptically-engaged nerve endings and of nerve fibers in passage. PMID- 1288064 TI - [Personality disorders in patients with panic disorder]. AB - The relationship between personality disorders and panic disorder in adults is analyzed in this study. The patients included in this work presented anxiety disorder with agoraphobia and were compared with a group of normal controls. The percentage of patients with personality disorder was 46% significantly higher than those encountered in the control group (16%). The existence of these disorders do not seem to modify the severity of panic disorder. PMID- 1288065 TI - [Profile of psychiatric and psychosomatic symptoms in medical students]. AB - In this paper the features, pattern profile and frequency of psychiatric and psychosomatic symptomatology of a sample constituted by 40 medical students during the usual academical period--free fron examination--are analyzed. Results suggest that there are no significant differences between the symptomatic patterns of the students of our sample and those belonging to the general population in our context. The Possible role played by stress associated to "examination" in reaching a high level of psychopathology in these students is discussed. PMID- 1288066 TI - [The influence of personality on suicidal behavior]. AB - With the purpose of studying the influence of personality on suicidal behavior, 63 female suicide attempters were assessed by means of standardized interviews, Eysenck's personality questionnaire (EPQ-R) and other psychometric scales. Personality disorders (DMS III-R) were found in almost 70 per 100 and associated with previous attempts, higher hopelessness, suicide ideation, and to a more severe attempt. The most relevant dimensions were psychoticism and extraversion. The first one correlated to repetition, hopelessness, and suicide ideation; the second exerted a moderating effect, showing association with feelings of conformity towards survival. Neuroticism showed a rather unspecific effect on studied factors. Results confirm a relationship between personality disorders and suicidal behavior, and suggest possible mediating variables. PMID- 1288067 TI - [Validity of the Spanish version of the Diagnostic Interview Schedule. Third revision (DIS-III-R)]. AB - After a brief description of the Diagnostic Interview Schedule, version III, spanish, we studied the agreement between diagnoses by a clinical standard and diagnoses by the DIS. As clinical standard we used the lifetime diagnoses given by expert psychiatrists to 135 patients who had been longitudinally assessed, with follow up periods amounting to 14 years. Sensitivities, for the fourteen diagnostic categories, varied between 64 per 100 and 100 per 100. Specificity was above 93 per 100 for all diagnoses, and K values ranged from .50 to 1.00, surpassing .60 for eleven of the fourteen categories. PMID- 1288068 TI - [Brief psychotherapy in clinical medicine patients]. AB - The criteria that "illness is biographical crisis od the individual" and that the only medicine is "personal medicine" is stressed. Clinical medicine, which covers medicine in its entirety, demands conceptual and doctrinal reaffirmations so that gradually the patient can come to be dealt with as a human being fron a holistic point of view, which commences with his complaint and consultation, continues with the interview and semiology, to finish with the diagnosis and therapy which, although in some cases it may be surgical, is still medical and integral. All the steps mentioned are bio-socio-cultural thus, whether in the practice of general clinical medicine or in the most specialized and technologically sophisticated clinical medicine, the animist component is not lacking and demands a minimum degree of "psychosomatic" Knowledge. The use of a psychotherapeutic technique is proposed which, while based on the psychoanalysis theory, is distanced technically from it as a "psychotherapy on limited time and goals", which abbreviates the disease, and is projected not as the "focus" of therapeutic work, but as a re-evaluation of the "life style" of each individual, and tends to help to develop a "project for life" suited to the possible personal, familiar and social well-being of the "patient". Technically speaking, this modality of brief psychotherapy is based on the nonuse of transferential interpretations, on impeding the regression od the patient, on facilitating a cognitice-affective development of his conflicts and thus obtain an internal object mutation which allows the transformation of the "past" into true history, and the "present" into vital perspectives. This technique is within reach of every health professional. PMID- 1288069 TI - [Psychopathologic manifestations in the sphere of subjectivity: disorders of self]. AB - As much as it strives to be "scientific" psychiatry can not obviate its necessary bonds to the subjectivity of the subject. The attempt has been made to reflect the richness of manifestation of subjectivity by means of a formalization process based on the traditional concept of it. This has led to the concept of disorders of self (Ichstorungen). They are of central importance in clinical psychiatry and psychopathology, as can be seen in the attempts to conceptualize schizophrenia. However, the presumed degree of precision reached runs parallel to the apartness of the fidelity to the effective vivification of the patient. This discord is interpreted as a fault in the conceptualization of the disorders of self and the possibilities originates by corporality point to the need to redefine, once again and in depth, the concept of subjectivity which is the foundation of psychiatry. PMID- 1288070 TI - [Psychophysiologic and psychopathologic aspects associated with sexual dysfunction]. AB - The authors review the relations between anxiety and sexual dysfunctions in base of studies that, in general, suggest the anxiety is common among subjects with sexual dysfunctions, but the level and the nature of the anxiety could vary much in the interindividual pattern. It revises experimental and clinical works that describe the anxiety provides the sexual arousal, studying the neurophysiological and neurochemical substratum which compares anxiety and sexual responses. It discusses the presence of psychopathology associated with sexual dysfunction. PMID- 1288071 TI - Photothrombosis in rabbit brain cortex: follow up by continuous pO2 measurement. AB - Continuous recording of changes in local pO2 during and after brain infarction in surviving animals which can be followed for months or years, may provide interesting information concerning pathophysiology and treatment of stroke and thrombosis. We performed such measurements before, during and till 4 weeks after photochemical induction of a cerebrocortical infarction in three rabbits. Rose bengal--a photosensitive dye which sticks to endothelial cells and gives rise to endothelial damage and thrombosis when illuminated--was injected intravenously. After injection, a circular area (diameter 3 mm) of the brain cortex was illuminated using an optic fiber conducting light from a halogen lamp, whether or not filtered by heat and colour filters. In order to enable pO2 measurement in and near the infarct zone, we constructed a transparent plastic frame in which pO2 electrodes were fixed beneath and 1 mm besides a shaft permitting mounting of the optic fiber. A black adhesive ring (inner diameter 3 mm) was attached to the bottom of the frame providing a perfectly demarcated illumination area. After fixation the electrodes were calibrated and the frame was implanted in the rabbit's skull. Ten days later an infarction was induced; pO2 was monitored continuously before, during and till 4 hours after this induction. Furthermore, pO2 was recorded 24 hours, 48 hours, 5 days, 14 days and 4 weeks after infarction. Parameters describing the time course of pO2 were determined. In the illuminated area pO2 decreased after a certain latency time to reach a very low level, probably zero level, where it remained for at least 24 hours. Gradually, recovery was observed during the following days, and four weeks after infarction both level and pattern of electrode current appeared to be normal again. In the border zone pO2 decreased but did not reach zero level. Recovery was observed earlier than in the illuminated area. PMID- 1288072 TI - Intravitreal and intraretinal oxygen tension in the rat eye. AB - We have successfully measured the intravitreal and intraretinal oxygen distribution in normal rats, during both normoxia and hyperoxia. The feasibility of such measurements in the very small rat eye has opened up the opportunity for the use of the many rat models of vascular disease in physiological experiments of retinal oxygen supply and consumption. PMID- 1288073 TI - Picosecond time of flight measurement of living tissue: time resolved Beer Lambert law. PMID- 1288074 TI - Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing. AB - The Differential Pathlength Factor (DPF) has been measured for several different tissues. The results showed that the DPF varied with the type of tissue studied, and in the case of the adult calf with sex. However, the DPF for all tissues studied was constant once the inter optode spacing exceeded 2.5 cm. Thus, measurements can be made by NIR spectroscopy at a range of inter optode spacings, and a single DPF used in the calculation of chromophore concentration. The results also showed that the major source of error in the DPF lay in the measurement of the inter optode spacing. To improve accuracy, two options are possible. Firstly, some means of continuous measurement of inter optode spacing could be incorporated in the NIR instrumentation. The better alternative would be an instrument incorporating a method of directly measuring the optical pathlength at each wavelength. This could be done either by time of flight measurement, or if it can be validated, by phase shift measurement. PMID- 1288075 TI - Near-infrared imaging in vivo (I): Image restoration technique applicable to the NIR projection images. AB - To enhance spatial resolution of NIR projection images in vivo, we performed refocusing of NIR projection images of human forearm of about 50 mm thickness. A volunteer's forearm was illuminated by parallel light beam-flux, and then projection images at 750 nm was measured with a Pertier-cooled CCD video camera and digitized. For refocusing computation, PSF of the light transmitted through the tissue was calculated by general equation proposed by van der Zee and Delpy (1988). Simple inverse, constrained least squares, and Wiener filters were tested as refocusing algorithms. Wiener filter gave the best result in terms of image quality and computation time. By applying Wiener filter to the image refocusing of NIR projection images of human forearm, we obtained enhanced spatial resolution. PMID- 1288076 TI - Muscle oxygenation by fast near infrared spectrophotometry (NIRS) in ischemic forearm. AB - Fast scanning near infrared spectroscopy (680-1050nm) was utilized to evaluate human forearm muscle oxygenation in 15 adults volunteers. Spectra were recorded in hypoxic hypoxia, ischemia and venous outflow restriction. Derivative spectra were performed with the aim to obtain a quantitative information of Hb/Mb oxygen saturation free from volume and scattering changes. The absorption spectra O.D. demonstrate an increase of deoxy-Hb/Mb in hypoxic condition with a moderate volume changes. In ischemia a rapid Hb/Mb desaturation occurred until a plateau was reached at 4th min. The cuff release was followed by hyperemia with Hb volume raise and oxy-Hb/Mb increase above the control. Spectral data support the hypothesis that derivative NIRS can be used to identify muscle oxygenation changes. PMID- 1288077 TI - Near-infrared imaging in vivo (II): 2-Dimensional visualization of tissue oxygenation state. AB - By measuring NIR projection images at 700 and 800 nm, we examined 2-dimensional visualization of Hb oxygenation state in the human forearm of about 50 mm thickness. Equations for selective quantification of oxy-Hb, deoxy-Hb, and SO2 were derived from in vitro experiment, and validity of the equations were checked by using a test phantom which simulates optical properties of living tissues. Forearm occlusion caused increase in 2-dimensional O.D. image at 700 nm, while slight decrease was observed in the image at 800 nm. These results were consistent with changes in NIR spectra caused by the forearm occlusion and explained by Hb deoxygenation and slight decrease in blood volume. Although several uncertain errors seemed to remain in our results, we obtained an essentially reasonable image which demonstrates 2-dimensional changes in Hb oxygenation in the human forearm caused by forearm ischemia. PMID- 1288079 TI - On-line oxygen uptake measurement (VO2): a computer feed-back controlled rebreathing circuit for long term oxygen uptake registration. AB - A totally closed feed back controlled anesthesia- and ventilation circuit has been developed feasible to be applied for artificial ventilation with tidal volumes as low as 5 ml at a rate of up to 60/min and for spontaneous ventilation with on-line measurement of physiological lung parameters (pressure, volume, flow). Oxygen inflow is regulated via actual-set value comparison, oxygen inflow is measured and recorded on-line (= oxygen uptake by the connected subject). On line oxygen uptake (consumption) measurement furnishes a valuable, so far not available parameter to monitor changes in the oxygen transport chain to the tissue and to register physiological oxygen consumption values and derangement of metabolism. First results show that total body oxygen consumption of man in rest is lower than so far expected in the high weight and body surface area groups and that oxygen consumption is decreasing with length and age. Metabolic derangements such as in developing hyperthermia crisis are noticed in a very early stage when therapy is still possible before severe damage has occurred. PMID- 1288078 TI - Monitoring of the oxygen pressure in the blood of live animals using the oxygen dependent quenching of phosphorescence. AB - Oxygen dependent quenching of phosphorescence is a powerful new method for measuring oxygen pressure in biological systems (see Vanderkooi et al, J. Biol. Chem. 262 (1987) 5476; Wilson et al, J. Biol. Chem. 263 (1988) 2712). This technology has now been extended to include measurements of the phosphorescent of oxygen probes dissolved in the blood as a complex with albumin. In this communication, we report on a new microcomputer controlled phosphorimeter in which the tissue is illuminated by a flash lamp and the phosphorescence observed through flexible light guides designed to make measurements in regions down to approximately 1 mm in diameter. Measurements of the phosphorescence lifetimes of these probes in regions of tissue necessarily report a distribution of oxygen pressures due to the presence of blood in veins and arteriols as well as that present in the capillaries. Thus the phosphorescence decay is the sum of a continuum of exponentials with different decay constants and initial intensities. The complete phosphorescence decay curve is digitized using a 12 bit, 1 MHz A/D board and deconvoluted using numerical methods to yield a distribution of exponentials contributing to the total decay curve. PMID- 1288080 TI - Oxygen delivery (DEL O2) dependent and independent oxygen consumption (VO2). PMID- 1288081 TI - Interaction of blood flow, diffusive transport and cell metabolism in isovolemic anemia. AB - 1) High blood flow can compensate for half-normal hematocrit, leaving the rate at which O2 is offered to the capillaries unchanged. Nevertheless, intracellular PO2 is lower in anemia, indicating impaired diffusive transport. 2) Anemia increases O2 flux per red cell and decreases functional capillary surface area. These changes increase flux density and the extracellular component of resistance to diffusive O2 transport, in accord with current theory (Federspiel and Popel, 1986; Groebe, 1990; Hellums, 1977). 3) Maintenance of diffusive flux in presence of anemia required a larger delta PO2 between Hb and Mb, and higher intracellular O2 conductance brought about by greater Mb-facilitated diffusion. Both compensations depend on lower PmbO2. 4) PmbO2 and creatine charge fall with increasing VO2 and ATP demand. These responses, as well as adaptive changes in redox help maintain VO2 in the presence of a lower O2 drive on electron transport. 5) Greater engagement of reserves of both transport and metabolism limits the range of aerobic performance in anemia. 6) The match between the transcapillary and mitochondrial O2 fluxes depends on interaction of transport and metabolism as a system. PMID- 1288082 TI - Microtopographic analysis of oxidative stress in organ microcirculatory units. AB - Current approaches for visualization of oxidative stress in organ microcirculatory units were summarized. Recent development of digital imaging photonic microscopy has made it possible to analyze spatial and temporal alterations of oxyradical generation during tissue injury. Luminol-dependent photonic imagery revealed granulocyte-mediated oxidative stress during microvascular damages, suggesting that the interface between venular endothelium and sticking granulocytes may be the most critical site of oxidative stress. Fluorographic analysis assisted by dichlorofluorescin (DCFH) diacetate is a powerful tool to visualize intracellular hydroperoxide formation. This method demonstrated intralobular heterogeneity of oxidative stress in the isolated perfused hepatic microcirculatory units exposed to either CCl4 or low-flow hypoxia. CCl4 caused the activation of dichlorofluorescein (DCF) predominantly in perivenular areas, while the 25% low-flow perfusion induced periportal or midzonal DCF activation. Refinement of the present technique will provide further insight into the microtopographic correlation between oxidative stress and tissue breakdown in microcirculation. PMID- 1288083 TI - Cytochrome P-450 under conditions of oxidative stress: role of antioxidant recycling in the protection mechanisms. PMID- 1288085 TI - Morphometric methods for the evaluation of capillary grouping patterns in rat heart. PMID- 1288084 TI - Ischemia-reperfusion injury and free radical involvement in gastric mucosal disorders. PMID- 1288086 TI - Estimation of the oxygen gradient across phospholipid bilayers of mitochondria from reperfused rabbit hearts after ischemia. AB - Mitochondria isolated from myocardium exposed to 30 minute ischemia followed by 30 minute reperfusion showed an increase in membrane viscosity and a decrease in wobbling angle of phospholipids, compared with those from the normally perfused myocardium in anesthetized open-chest rabbits. The values for the membrane viscosity were used to estimate the oxygen gradient across the lipid bilayers of mitochondrial membranes with a model of cylindrical diffusion. The effective diffusion coefficient for oxygen, DO2, was approximated to be 6.5 and 6.3 x 10( 5) cm2/sec in the control and ischemic-reperfused area, respectively, by comparing reported DO2 values with values for membrane viscosity. For the surface area of the inner mitochondrial membrane including cristae and for the oxygen consumption rate of the myocardium, reported values for rats and cats, respectively, were employed. Using these values, oxygen gradients across the lipid bilayers of mitochondrial lipid membranes were estimated to be only 0.055 and 0.057 nM in the control and 30 minute ischemic-reperfused myocardium, respectively. If the mitochondrial membranes are hydrated because of the ischemia reperfusion, the absorption coefficient of the membrane to oxygen will decrease and the oxygen gradient will be increased. In the present study, however, the fluorescence life time of DPH, the hydrophobic fluorophore, showed no shortening despite the ischemia-reperfusion. Hence, no indication of membrane hydration was obtained. PMID- 1288087 TI - The oxygen dependence of mitochondrial oxidative phosphorylation and its role in regulation of coronary blood flow. AB - The oxygen dependence of mitochondrial oxidative phosphorylation measured in isolated cells of cardiac and non-cardiac origin are affected by the metabolic state of the cells. The contribution of oxygen diffusion to the measured P50 value in resting cells is small. In cardiac myocytes, and possibly in the other cells as well, this contribution may become significant near maximal levels of respiration. The influence of cellular energy metabolism on the oxygen dependence of respiration in cardiac myocytes suggests strongly that mitochondrial oxidative phosphorylation in these cells is an oxygen sensor for adjusting coronary vascular tone during normal cardiac function. PMID- 1288088 TI - Oxygen penetration in and release from lung surfactant. AB - The kinetics of oxygen penetration from the air into an oxygen free human BAL/saline and of its release from the oxygenated BAL/saline into a nitrogen environment was studied. Time-dependent oxygen concentration at constant temperature was monitored by recording the direct polarographic current of the second reduction wave of oxygen at a dropping mercury electrode. The obtained kinetic curves showed that not only uptake and release were quicker in BAL than in saline but also the corresponding equilibrium values were higher. Release and uptake curves in BAL were markedly different. The release was faster than the uptake but its maximal value was about 30% under the maximal uptake level. We suggest that the differences in oxygen uptake and release kinetics might contribute to explain the previously found accumulation of oxygen in BAL. The positive difference between the release and uptake kinetics at the beginning of the curves is consistent with a steady oxygen penetration through the BAL. The difference in the maximal oxygen uptake level and the maximal release level indicates a partial retention of the oxygen in the system. PMID- 1288089 TI - Improvement of pulmonary gas exchange after surfactant replacement in rats with Pneumocystis carinii pneumonia. AB - The effect of intratracheal surfactant instillation on pulmonary function in rats with pneumocystis carinii pneumonia (PCP) was investigated. In these animals which developed PCP with severe respiratory failure after s.c. administration of cortisone acetate over 8-12 weeks, pulmonary function could be improved by surfactant instillation, as measured by an increase in PaO2. Histological examination showed that alveoli of rats with PCP which received no surfactant treatment are filled with foamy edema, whereas after surfactant treatment alveoli are stabilized and well-aerated. These results indicate that surfactant therapy could be used in patients with severe PCP to overcome an acute stage of respiratory distress while at the same time surfactant could serve as a carrier substance for antimicrobial drugs to attain high intra-alveolar and low systemic antimicrobial drug concentrations. PMID- 1288090 TI - Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury -significance of vasodilator prostanoids. AB - To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a significant rise in arterial PO2 from 84 to 99 Torr. The findings are highly compatible with the idea that HPV is distinctly attenuated in diseases areas induced by oleic acid probably due to a local accumulation of vasodilator prostanoids. Inhibiting prostanoid biosynthesis may selectively enhance the vascular reactivity to O2 in shunt vessels and may redistribute the perfusion from shunt to relatively normal areas, thereby improving gas exchange at alveolar region without altering the total amount of extravascular lung water. PMID- 1288091 TI - Modeling of oxygen transport to skeletal muscle: blood flow distribution, shunt, and diffusion. AB - By injection of embolizing microspheres, by local radioactive xenon clearance and by inert gas washout in resting and stimulated gastrocnemius dog preparation, experimental evidence for unequal blood flow distribution and for shunt flow has been provided. Model calculations show that in some respect unequal blood flow and shunt produce effects predicted for a homogeneous model with diffusion limitation of O2 supply. This finding must be taken into account when the role of diffusion limitation to O2 supply is to be ascertained. PMID- 1288092 TI - The role of wall shear stress in microvascular network adaptation. AB - The possible role of wall shear stress in microvascular network adaptation was investigated by computer simulation in planar polygonal model networks. Adaptation of vessel diameter to local wall shear stress resulted in false geometry and excessive rarefaction of the networks. Adaptation to mean wall shear stress decreased the range of shear stress, decreased the total power dissipation, and prevented network rarefaction. A measure of mean wall shear stress may serve as a control signal for the adaptation of vessel diameter to blood flow in microvascular networks. PMID- 1288093 TI - 99mTc-DTPA clearance: a sensitive method for early detection of an impending disturbance in gas exchange. PMID- 1288094 TI - Estimation of respiratory mechanics in dogs with acute lung injury. AB - In mechanically ventilated anesthetized dogs with acute lung injury induced by intravenous infusion of oleic acid (OA), changes in airflow, lung volume, and tracheal (Pao), transpulmonary (Ptp) pressures were measured. Changes in lung mechanics were studied before and after OA infusion at intervals, during an observation period lasting 4-5 hours, by using the interrupter technique and identification technique, and by measuring the pressure-volume (PV) characteristics. The main results are listed as follows: (1) compliance and FRC showed a marked decrease, Pao and Ptp showed a marked increase within 2 hours after OA. (2) airflow resistance estimated by the identification technique showed a marked increase after OA. (3) static PV characteristics of both the lungs and total respiratory system showed similar changes 4 hours after OA, characterized by the presence of an inflexion on the inflation limb, increased hysteresis and a rightward and downward shift of the loop. (4) the trend of changes of dynamic PV characteristics obtained by changing the PEEP value in a stepwise manner, with the ventilation uninterrupted, was similar to that of the static PV curve. It is suggested that an on-line identification technique with one-compartment model to track the slow changes in combination with serial measurements of the dynamic PV characteristics of the total respiratory system would be more appropriate for monitoring lung mechanics of ventilated patients with ARDS. PMID- 1288095 TI - Effect of hyperventilation on oxygenation of the brain cortex of neonates. AB - A new phosphorescence imaging method (Rumsey et al, Science (1988) 1649) has been used to continuously monitor the oxygen pressure in the blood of the cerebral cortex of newborn pigs. The animals' blood pressure was continuously measured and PaCO2, PaO2 and arterial blood pH were measured periodically. The oxygen pressure in the blood was quantitatively determined for regions of about 100 um square within the image (from a total field of about 3 mm diameter). It was observed that during hyperventilation, which lowered PaCO2 and increased pH of the blood, oxygen pressure decreased in proportion to the decrease in PaCO2. For example, hyperventilation which decreased PaCO2 from its normal value of 40 Torr to 10 Torr caused a rapid (within 5 minutes) decrease in oxygen pressure in the blood of capillaries and veins to approximately 1/4 of normal. PMID- 1288096 TI - Hypoxia and the "reaction theory" of central respiratory chemosensitivity. AB - In peripherally chemodenervated and vagotomized cats and rabbits, either spontaneously breathing or artificially ventilated, we studied the reaction of the respiratory control system to changes in the extracellular fluid (ECF) pH at the ventral surface of the medulla oblongata. The brainstem ECF-pH was varied either by alternating periods of hypoxia and hyperoxia or by intravenous infusion of lactic acid to achieve endogenous or exogenous lactacidosis, respectively. Additionally, the arterial PCO2 was changed by varying the inspiratory CO2 fraction or the respirator's pumping rate. When pulmonary ventilation or central respiratory drive (in terms of phrenic nerve activity) was related to brainstem ECF-pH, no unique function resulted for respiratory (CO2-induced) and metabolic (lactic acid induced) acid-base changes, thus contradicting the "reaction theory" for central respiratory chemosensitivity. Under steady state conditions, there was no ventilatory reaction to endogenous or exogenous metabolic brainstem acidosis at all. However, the apneic threshold was shifted towards the acid range, although the sensitivity of the respiratory system to CO2 remained nearly unchanged, no matter whether CO2 was inhaled or increased by acetazolamide. This points to a dominating role of CO2 or at least carbonic acid over fixed acids for the central chemosensitive control of pulmonary ventilation. PMID- 1288097 TI - Oxygenation of mammary tumors: from isotransplanted rodent tumors to primary malignancies in patients. AB - As a result of a compromised and anisotropic microcirculation, isotransplanted mammary tumors in mice exhibit hypoxic and anoxic tissue areas which are heterogeneously distributed within the tumor mass. Similarly, in poorly perfused human breast cancer xenografts, hypoxia develops at early growth stages and expands with tumor growth. In contrast, breast cancer xenografts with high perfusion rates exhibit an oxygenation status comparable to that of most normal organs. There is clear experimental evidence that the efficiency of tumor blood flow in isotransplanted tumors and in xenografted human breast cancers is the principal modulator of tissue oxygenation. The pO2 distribution found in primary lesions in patients ranged from the pO2 histograms obtained in "low-flow" isotransplants and xenografts to those measured in "high-flow" breast cancer xenografts or normal tissues. From our extended and systematic clinical studies there is clear indication that the oxygenation status of human breast cancers in situ does not correlate with the clinical stage and/or histological grade of an individual tumor. PMID- 1288098 TI - Measurements of tumor blood flow using intraperitoneal deuterium and 2H-NMR spectroscopy. AB - Using i.p. delivered deuterated water, and 2H NMR spectroscopy, it is possible to non-invasively, serially, and quantitatively measure blood flow through tissue volumes as small as 0.05 ml. Measurements made with this technique show that changes in total tumor blood flow reflect local changes measured superficially by laser Doppler flowmetry, and that tumors of identical histology and size have heterogeneous blood flow rates. Finally, we have shown that tumors growing in an irradiated normal tissue have a lower blood flow rate which is manifest when tumors grow beyond 0.1 ml. PMID- 1288099 TI - Apparent heterogeneity between leukemic lymphocyte cell lines. AB - 31P-NMR and polarographic techniques were used to investigate glycolytic versus aerobic oxidative activity in normal and leukemic lymphocytes, and to investigate possible heterogeneity in these parameters between two leukemic cell lines. Molt 3 cells showed a 10-fold higher rate of glutamine-dependent respiration than Molt 4 cells, and an increased level of glutamine-uptake. Molt 3 demonstrated a high intracellular buffering capacity, manifested by constant pHi after addition of glucose, while the same treatment applied to Molt 4 cells induced a change in internal pH of up to 1.23 pH units. This data raises the possibility of heterogeneity of leukemic lymphocytes within the patient from whom the isolation was conducted, or of gross metabolic adaptation by the cell lines in culture. PMID- 1288100 TI - Whole body and regional O2 uptake/delivery and lactate flux in endotoxic dogs. AB - We infused endotoxin into anesthetized dogs while maintaining cardiac output. Whole body O2 uptake and arterial lactate concentration were measured at the same time with regional O2 uptake and lactate fluxes in muscle and gut. Even though whole body O2 uptake increased, so did arterial lactate levels. The different behavior of organ systems was marked by the fact that muscle took up lactate while its O2 uptake didn't change whereas gut produced lactate as it decreased its O2 uptake. Comparison with critical levels of O2 delivery and O2 extraction ratio for whole body and the two regions opened considerable doubt that generalized and significant hypoxia explained the rise in arterial lactate. Addition of mild hypoxic hypoxia also neither caused O2 uptake to fall nor lactate to rise which reinforced our conclusion that there was little or no tissue hypoxia in endotoxin treated animals given adequate resuscitation with red blood cells and colloid solutions. PMID- 1288101 TI - Resuscitation fluids and oxygen transport in haemorrhagic shock. AB - This study examined the cardiovascular and oxygen transport/consumption relationships in haemorrhagic shock and resuscitation using Human Albumin and Gelatin solutions in a porcine haemorrhagic shock model. Immature pigs (17-25 kg) were anaesthetised and ventilated with nitrous oxide, oxygen and isoflurane. Aortic pressure monitoring and monitoring of pulmonary pressures and cardiac output via a Swan-Ganz catheter were instituted. A controlled haemorrhage of 40% of blood volume at 1% blood volume per minute was followed 30 minutes later by resuscitation with 60% of blood volume of 4.5% Human Albumin (Immuno) or 4% Modified Fluid Gelatin (Gelofusine). Haemorrhage caused marked decreases in (CI), mean arterial pressure and oxygen delivery (DO2). Oxygen consumption (V02) remained unchanged. Resuscitation with Albumin and Gelatin raised CI to values 60% to 70% above control though only Albumin restored DO2. Deterioration was more rapid in the Gelatin group due to the estimated half a life of 3 hours in this model. Oxygen extraction was 10% higher in the Gelatin group 2 hours after resuscitation. The role of oxygen radicals in haemorrhagic shock is discussed. PMID- 1288102 TI - Changes in tissue histology associated with adaptation and acclimation to hypoxia. AB - Newborn kittens are adapted to hypoxia by having an oxygen department respiration rate. In part, this is due to the structure of the liver which results in a great reduction of oxygen consumption in this organ in response to hypoxia. Older animals possess an oxygen independent respiration rate which is not lost when they acclimate to hypoxia. Instead, there are histological changes which permit the liver to consume oxygen at the same rate as before by facilitating intracellular oxygen transport. PMID- 1288103 TI - Impact of ischemia on tissue oxygenation and wound healing: improvement by vasoactive medication. AB - The influence of vasoactive medication on tissue oxygenation and wound healing was investigated in the ear model of the hairless mouse. Ischemia was induced to the ears by ligating 2 of the 3 main vessel bundels and verified by measurements of tcpO2. Reduced tissue oxygenation was followed by a prolongation of the time required for complete healing of standardized wounds. Treatment with the vasoactive drug Buflomedil (3 mg/kg/day iv.) resulted in enhanced recovery of the tissue from reduced oxygenation and likewise reversed the adverse effects of ischemia on wound healing. These results warrant the use of the drug in patients suffering from delayed wound healing due to peripheral arterial disease. PMID- 1288104 TI - PAF-acether induced arterial thrombosis and the effect of specific antagonists. AB - Platelet-vessel wall interactions and local thrombosis are investigated in vivo in a branch of the mesenteric artery of the guinea pig, using optoelectronic registration and ultrastructural control. Following an electrical challenge resulting in changes of cell membrane polarization, subsequent superfusion by PAF acether or a stable analogue, (1-O-alkyl-2-N-methylcarbamyl-sn-glycero-3 phosphocholine, 10(-8) M focal concentration (f.c.)) for a restricted period results in endothelial cell retraction and bleb formation followed by platelet adhesion and the development of a thrombus which over time becomes invaded by leukocytes and eventually occludes the vascular lumen. It was demonstrated in a previous investigation that these phenomena are triggered by the generation of endogenous PAF-acether by the endothelial cells. Specific PAF-acether antagonists, such as BN 52021 a ginkgolide, but also synthetic molecules, derivatives of the triazolo-pyridino-diazepine group (BN 50727, BN 50755 and BN 50789), significantly inhibit platelet-vessel wall interactions and thrombosis, but not the formation of blebs in the endothelial cells. Hydrogen peroxide (10( 5)M f.c.) not only primes the effect of PAF-acether, but is by itself capable of inducing thrombosis through a PAF-acether-mediated mechanism. Inhibition of acetyl hydrolase by PMSF (phenyl-methyl-sulfonyl-fluoride, 10(-5)M f.c.) invariably results in a significant enhancement of thrombosis, while conversely, inhibition of acetyl transferase by 27584 RP (4-(naphtylvinyl)pyridine hydrochloride, 10(-6)M f.c.) inhibits thromboformation indicating that the remodeling pathway is involved. PMID- 1288105 TI - Development of an in vivo perfusion system for bovine fetal small intestine. PMID- 1288106 TI - A non-linear calculation method for in vivo estimation of sinusoidal oxygen saturation in the liver of rats. PMID- 1288107 TI - Human placental oxygen metabolism. PMID- 1288108 TI - The measurement of the diffusion coefficient of oxygen thorough small volumes of viscous solution: implications for the flux of oxygen through tissues. PMID- 1288109 TI - Studies of lymph and lymphocyte respiration to estimate tissue oxygen pressures and oxygen permeability of the lymph duct. PMID- 1288110 TI - Transcutaneous measurements of skin O2 supply and blood gases. AB - The data of the O2 exchange through the surface of the skin show that a part of the normal upper skin can be supplied with O2 from the surrounding atmosphere. This may be important in pathological situations although probably simultaneous disturbances of the substrate supply may be more serious. The noninvasive continuous registration of skin surface pO2 (and pCO2) allows to monitor skin oxygen supply under different conditions. The new optical sensing of pssO2 and of the local O2 flux into the skin opens up new promising possibilities for quantification of the skin oxygen supply. PMID- 1288111 TI - Relating measuring signals from PO2 electrodes to tissue PO2: a theoretical study. AB - Organ surface PO2 measurement by oxygen sensitive electrodes has proved to be an efficient tool for monitoring changes in tissue oxygenation status. A parameter giving more direct information is the PO2 distribution within tissue cells which, however, can only be assessed by more invasive methods. The present study addresses the problem of relating electrode measured surface PO2 to muscle cell PO2. To that end, the magnitude of tissue volumes the PO2 in which electrodes are sensitive to, has been reassessed. It turned out that the measuring signal of current membrane covered PO2 electrodes is only sensitive to the PO2 within the muscle surface and not any deeper, thus rendering the measured PO2 an area weighted average over the surface PO2 rather than a spatial average. The consequences of this finding are illustrated in an example of a maximally working muscle. Under the assumption that there are capillaries located on the muscle surface or immediately beneath it, the PO2 predicted to be measured by a surface electrode is almost four times the average muscle fiber PO2. However, PO2 values actually measured by surface PO2 electrodes are even higher calling for further explanation, in which superficial blood vessels and surface fascia may play an important role. Quantitative information on vascular morphology near muscle surfaces is needed in order to more definitely determine the importance of mechanisms discussed, for experimental results. PMID- 1288112 TI - A new catheter for quasi-continuous measurement of arterial partial oxygen pressure. AB - Recently a catheter has been developed based on amperometric measurement principle for in vivo monitoring of PaO2. A study in pigs was performed to compare the cell with a standard method for measuring PaO2. The results show that the cell is capable to accurately measure PaO2. PMID- 1288113 TI - Continuous intra-arterial PO2 monitoring during thoracic surgery. AB - Intermittent blood gas sampling has several disadvantages, the most important being that samples are usually taken at set intervals, or when changes in oxygenation are suspected--when it is too late. Another problem is inaccuracy caused by careless blood sample handling. Continuous intravascular PaO2 monitoring eliminates these problems. This study shows that the Continucath sensor is an easy-to-use and reliable monitor, with specific early warning capabilities for hypoxia, thereby improving anesthetic and intensive care management. Its characteristics are: a stabilization period of 10 minutes, a 90% response time of 90 seconds, temperature dependence of 4% per degree celsius, a flow dependence of less than 1% if the flow is more than 5 cm/sec, a drift of less than 0.7% per hour, a correlation coefficient of 0.92 when compared to blood gas analysis during surgery. PMID- 1288115 TI - Proceedings of the 19th Annual Meeting of the International Society on Oxygen Transport to Tissue. Willemstad, Curacao, August 24-30, 1991. PMID- 1288114 TI - Construction, calibration and evaluation of pO2 electrodes for chronical implantation in the rabbit brain cortex. AB - Aiming at continuous polarographic measurement of the mean pO2 in the rabbit brain cortex before, during and after photochemically induced infarction, we designed and constructed monopolar platinum oxygen electrodes of the open type for chronical implantation. The measuring tip (length 1 mm, diameter 0.1 mm) is covered with a homogenous membrane of cellulose acetate. The electrode currents are measured by a four-channel amplifier of proper design; the device permits accurate and stable polarisation, identical for each channel. Moreover, a calibration device has been constructed. It consists of a Buchner funnel filled with Ringer solution and mounted in a temperature-controlled bath. In order to create a specific partial pressure of oxygen in the calibration chamber, predetermined gasmixtures are bubbled through the solution using computer controlled mass flow regulators. The calibration device thus permits the determination of primary and secondary electrode parameters, i.e. linearity, oxygen sensitivity and residual current, and polarisation dependency, temperature dependency, sensitivity to CO2, electrode stability, dynamic behaviour and oxygen consumption. Three groups, each of them containing ten electrodes, have been tested with regard to electrode parameters: the first group contains bare electrodes, the second and the third group contain membrane covered electrodes, with a membrane thickness of 10 and 20 microns respectively. In order to evaluate acute and long-term effects of implantation on the brain cortical tissue and on the sensors' measuring qualities, electrodes have been implanted for different time periods (51 days, 30 days, 9 days, 5 min). pO2 was recorded regularly and polarograms have been registered. The effects on cortical tissue have been studied with the aid of light microscopy. PMID- 1288116 TI - Rat brain adaptation to chronic hypobaric hypoxia. PMID- 1288118 TI - Whole lung lavage under hyperbaric conditions: 2. Monitoring tissue oxygenation. PMID- 1288117 TI - Whole lung lavage under hyperbaric conditions: 1. The monitoring. PMID- 1288119 TI - Skeletal muscle PO2 in anaerobic soft tissue infections during hyperbaric oxygen therapy. AB - In the present study skeletal muscle PO2 measurements were performed in patients with gas gangrene and anaerobic soft tissue infections before, during and after hyperbaric oxygen therapy. Polarographic PO2 needle electrodes appeared to be suitable for application during different ambient pressures. We found that patients with gas gangrene revealed higher skeletal muscle PO2 values than patients with an anaerobic soft tissue infection. This may be explained by a higher metabolic rate within the anaerobically infected soft tissues. The higher PO2 values in gas gangrene may be caused by alpha toxins, affecting cellular and intracellular membranes thus destroying PO2 diffusion barriers. PMID- 1288120 TI - Effect of hyperbaric oxygen treatment and perfluorochemical administration on glutathione status of the lung. AB - Exposure to hyperoxia, especially under hyperbaric conditions, causes an enhanced oxidative stress particularly in lung tissue. To test the potential hazardous effect of either a single or repeated hyperbaric oxygen treatment (HBO) on the cellular defence system the glutathione status of lung tissue from rats exposed to HBO was investigated. When daily exposed to 2.5 ATA of > 95% O2 for 90 min over 8 or 14 days the content of reduced glutathione in lung tissue (GSH) increased by 16-19%. Oxidized glutathione (GSSG) tended to increase after 8 days and was 56% higher after 14 days. While the GSSG/GSH ratio was unchanged after 8 days, it increased by 39% after 14 days. Thus, the GSH increase after 8 days can be understood as a adaptive process to protect the lung from oxidative stress. The distinct increment of the cellular GSSG that lead to an increase of the GSSG/GSH ratio after 14 days reflects a situation, in which the cellular defence system is overwhelmed by oxidative stress. The additional pretreatment with perfluorochemicals in a dose of 2g/kg every second day aggravated the observed changes (GSH +39-19%, GSSG +118%). In a second experiment rats were exposed to a single session with 7 ATA of O2 for 60 min. GSH in the lungs increased for 40%, it was not elevated by PFC. However, GSSG increased to a much higher degree in untreated as well as in PFC-treated animals (+240%, +163%), elevating the ratio GSSG/GSH markedly (+145%, +176%). Allopurinol given as radical scavenger in a dose of 50 mg/kg was able to suppress the increased oxidative stress widely. Thus adaptive and overloading processes are involved under the treatment with increased oxygen pressures. As the administration of PFC aggravates the observed changes, a still increased blood oxygen offer must be considered as the causative agent. A radical scavenger is capable to suppress the increased oxidative stress widely. PMID- 1288121 TI - Blood flow and tissue oxygenation of human tumors: an update. PMID- 1288122 TI - Computerized histographic oxygen tension measurements of murine tumors. AB - As further work on tumor oxygenation results in the development of agents capable of modulating hypoxic cell radiosensitivity, and chemotherapeutic agents capable of targeting hypoxic cells, knowledge of relative tumor oxygenation takes on greater importance. The pO2 Histograph was used to characterize the oxygen tension of a murine sarcoma (RIF1) and a murine carcinoma (SCCVII), each with different hypoxic fractions. These tumors were studied sequentially to assess the suitability of the Histograph both as a research tool and, ultimately, as a clinical monitor of tumor hypoxia. PMID- 1288123 TI - Oxygenation and bioenergetic status of murine fibrosarcomas. PMID- 1288124 TI - Measurement of human tumor blood flow: a positron technique using an artifact of high energy radiation therapy. PMID- 1288125 TI - Improving the effectiveness of the bioreductive antitumor agent SR 4233 by induced hypoxia. PMID- 1288126 TI - A computer simulation of oxygen partial pressure and temperature profiles during hyperthermia. PMID- 1288127 TI - Oxygen dependent quenching of phosphorescence: a perspective. AB - Oxygen quenches phosphorescence by energy transfer from the phosphor when oxygen molecules collide with molecules of the phosphor in the excited triplet state. Thus increasing oxygen pressure causes an increase in the rate of decay of phosphorescence (shorter lifetimes) and a decrease in total phosphorescence intensity. Phosphors have been selected which decay with a single exponential and for which the relationship between phosphorescence lifetime and oxygen pressure is quantitatively described by the Stern-Volmer equation. The use of phosphorescence lifetime as the measure of oxygen pressure makes the method insensitive to the absorbance changes of other chromophores in the system. This method has permitted quantitative, rapid (less than 10 msec) and sensitive (to less than 10(-8) Torr) measurements of oxygen pressure in suspensions of cells or subcellular organelles. In tissues, oxygen pressure has been evaluated by measuring phosphorescence using an intensified CCD camera. Maps of oxygen pressure in the vasculature of the cortex of the brain and of other tissues demonstrate the method is limited only by the optics of the system and resolutions of a few microns are readily attained. PMID- 1288128 TI - Basic mechanisms of diffusive and diffusion-related oxygen transport in biological systems: a review. PMID- 1288129 TI - Can the flow dependency of the polarographic PO2 electrode be used to measure arterial PO2 and local capillary flow transcutaneously? PMID- 1288130 TI - Measurement of cerebral blood flow in adult humans using near infrared spectroscopy--methodology and possible errors. PMID- 1288131 TI - Design and evaluation of a reflectance oxygen sensor in critically ill patients. PMID- 1288132 TI - Analysis of multiple multipole scattering by time-resolved spectroscopy and angular dependent spectrometry. PMID- 1288133 TI - In vivo NADH and Pd-porphyrin video fluori-/phosphorimetry. PMID- 1288134 TI - In vivo NADH fluorescence. PMID- 1288135 TI - Quantitation of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry. AB - Photon migration in highly scattering tissues such as muscle and brain gives optical pathlengths that are dependent upon absorption and scattering parameters, mu a, mu s'. Determination of these parameters gives the correct concentration of principal absorber such as hemoglobin in the red region of the spectrum. Determinations of scatter factor in functioning and pathological tissues are made. PMID- 1288136 TI - Bioengineering: the fifth traditional engineering discipline? PMID- 1288137 TI - Evaluation of the algorithm used in near infrared spectrophotometry. PMID- 1288138 TI - Informative imaging of oxygen supply parameters in clinical practice. PMID- 1288139 TI - Diffusion limitation of oxygen in heterogeneous lung and tissue models. PMID- 1288140 TI - Gas exchange in the lung, computer feed back controlled physiological matching of artificial ventilation. PMID- 1288141 TI - Non-invasive, on-line measurement of oxygen consumption during anesthesia. AB - Oxygen consumption is usually derived from values measured by a thermodilution catheter, i.e. an invasive procedure, with associated risks and calculation errors. Closed circuit ventilation provides a reliable, non-invasive means of access to this parameter of metabolism. Routine application of closed circuit ventilation requires overcoming many, mainly technical, difficulties (e.g. leakage problems, valve malfunctions, and calculations of gas uptake). We developed a computerized closed circuit anesthesia ventilator without these problems. With this system non-invasively measured oxygen uptake is continuously presented on-line. We discuss three representative patients presenting for surgical repair of an abdominal aneurysm. Besides actual changes in metabolism and depth of anesthesia, success or failure of the operation is visible in the pre- and direct post-clamping period. With resuscitative therapeutic interventions, increase in oxygen consumption gives valuable information under changing conditions. We conclude that closed circuit anesthesia is a safe and valuable method for measurement of oxygen consumption. PMID- 1288142 TI - Oxygen transport through a model lung surfactant surface layer: influence of the film compression on the kinetics. AB - The influence of the compression state of a model Lung Surfactant Surface Layer LSSL on the oxygen permeation kinetics was studied in vitro at 37 degrees C. In an attempt to mimic in vivo conditions, the oxygen from the air was allowed to cross a dipalmitoylphosphatidylcholine DPPC layer situated at an air/deaerated saline interface in an electrochemical vessel. The time dependent concentration change of the oxygen diffusing through this layer into the deaerated saline hypophase was measured electrochemically using a Hanging Mercury Drop Electrode HMDE, situated at a definite depth in the bulk of the saline. The surface pressure in the monolayer was monitored using a Wilhelmy balance. The oxygen permeability was measured through two differently compressed DPPC layers in which the area/phospholipid molecule differed by 30%. This is consistent with the difference in the alveolar area at the end-points of the compressed and expanded lung. The results, submitted to a linear regression analysis, showed that the DPPC film compression influences the oxygen permeation kinetics. The denser the lipid film, the slower the oxygen uptake by the deaerated hypophase. The results suggest that the LSSL might play an important role in the oxygen transport kinetics, the oxygen permeation through it being dependent on the actual lung area. PMID- 1288143 TI - Different surfactant treatment strategies for respiratory failure induced by hydrochloric acid aspiration in rats. PMID- 1288144 TI - Oxygen supply dependency in the critically ill--a continuing conundrum. AB - There was little dispute that endotoxin treatment of experimental animals could recreate the O2 extraction defect that had been observed in critically ill patients. The remaining question was whether or not this necessarily signified pervasive tissue hypoxia. Some limitation to O2 diffusion in the tissues had been postulated because of known effects of endotoxin that ultimately result in damage to endothelium. We were unable to alter the critical DO2 or 0(2)ER in endotoxic dogs by manipulating the arterial PO2. This tended to rule against there being a diffusion limitation created by the endotoxin as a result of endothelial disruption or microvascular dysfunction. The results of the DCA and dopexamine experiments served to remind us that arterial lactate measurements may or may not indicate widespread tissue hypoxia. Sepsis, as emulated by endotoxin infusions, is also a metabolic disease that can cause inactivation of PDH and thus cause lactacidosis without tissue hypoxia. Regional measurements of lactate flux indicated that gut was hypoxic in spite of DO2 above critical because of maldistribution of blood flow between muscularis and mucosa. The questions persist of how much tissue hypoxia is caused by sepsis or endotoxin when DO2 is supported at supposedly adequate levels and whether there are marked regional differences. Such questions still await answers. Newer technological advances that permit assessment of tissue oxygenation by noninvasive methods, such as near infrared spectrophotometry or nuclear magnetic resonance measurement of tissue energy potential, may soon be feasible in critically ill patients. This kind of information will be of vast importance in designing the most effective therapeutic regimen. PMID- 1288145 TI - Gas exchange uniformity within individual lung lobes. PMID- 1288146 TI - Effect of artificial ventilation on pulmonary antioxidant enzyme activities in a congenital diaphragmatic hernia rat model. PMID- 1288147 TI - Comparison of pressure support ventilation (PSV) and intermittent mandatory ventilation (IMV) during weaning in patients with acute respiratory failure. PMID- 1288148 TI - Alterations of the respiratory minute volume cause changes in muscle oxygenation of rats. AB - In the anesthetized, open-chest rat, alterations of the respiratory minute volume were induced by changes of the respiratory frequency. Mean tissue pO2 of skeletal muscle in healthy and distressed rats did not change significantly. 10 minutes after a ventilation stop lasting 60 seconds, healthy rats showed an approximately normalized pO2 histogram, whereas distressed rats did not seem to recover. The results indicate an independent regulation mechanism which maintains a sufficient oxygen supply to skeletal tissue of anesthetized rats. The efficacy of this mechanism seemed to be reduced in distressed rats after the ventilation stop. PMID- 1288149 TI - Optical measurements of oxygen and electrical measurements of oxygen chemoreception in the cat carotid body. PMID- 1288150 TI - Dose-dependent improvement of gas exchange by intratracheal perflubron (perfluorooctylbromide) instillation in adult animals with acute respiratory failure. PMID- 1288151 TI - Gas exchange and lung mechanics during long-term mechanical ventilation with intratracheal perfluorocarbon administration in respiratory distress syndrome. PMID- 1288152 TI - Perflubron (perfluorooctylbromide) instillation combined with mechanical ventilation: an alternative treatment of acute respiratory failure in adult animals. PMID- 1288154 TI - A new device for the oxygenation of patients: the "NasOral-System". PMID- 1288153 TI - Clinical use of oxygen stores: pre-oxygenation and apneic oxygenation. PMID- 1288155 TI - Hemodilution and oxygen transport. PMID- 1288156 TI - Second generation fluorocarbons. PMID- 1288157 TI - Properties of chemically cross-linked hemoglobin solutions designed as temporary oxygen carriers. PMID- 1288158 TI - Elaboration of fluorocarbon emulsions with improved oxygen-carrying capabilities. PMID- 1288159 TI - Oxygen uptake in the lungs under pathological conditions and its therapeutic efforts. PMID- 1288160 TI - The respiratory potential of oxygen: a new quantity to characterize state, effects and bio-availability of the gas in organism. PMID- 1288161 TI - Facilitation of oxygen transfer by perflubron in hemodiluted dogs. PMID- 1288162 TI - Monitoring of intracapillary HbO2 in foetal scalp during delivery. PMID- 1288163 TI - O2 transport during exercise after cardiac transplantation. PMID- 1288164 TI - Effect of low dose oxygent added to blood on muscle VO2max. PMID- 1288165 TI - Fetal oxygenation in chronic maternal hypoxia; what's critical? PMID- 1288166 TI - The relation of oxygen delivery to utilization during liver transplantation: is there a critical value? PMID- 1288167 TI - Comparative study of the accuracy of two fiberoptic mixed venous saturation catheters (Spectracath vs Opticath) during acute changes in hematocrit and cardiac output in humans. PMID- 1288168 TI - Erythropoietin induction by hypoxia. A comparison of in vitro and in vivo experiments. PMID- 1288169 TI - Altered concentrations of aldosterone in neonatal calves during chronic hypoxia and the subsequent recovery period. PMID- 1288171 TI - Regional cardiac hemodynamics and oxygenation during isovolemic hemodilution in anesthetized pigs. PMID- 1288170 TI - Myocardial oxygen supply under critical conditions, the effects of hemodilution and fluorocarbons. AB - This article reviews the factors influencing myocardial oxygen supply and demand. The regulative mechanisms in coronary blood flow, especially in critical conditions, are explained. Myocardial oxygenation in coronary artery disease is discussed with special reference to pharmacological intervention. An extensive evaluation of the effects of hemodilution on both the healthy and diseased heart is presented. Effects of hemodilution with fluorocarbons for the treatment or prevention of myocardial ischemia are shown with the aid of intramyocardial oxygen partial pressure measurements. PMID- 1288172 TI - Artificial oxygen carrying blood substitutes. PMID- 1288173 TI - Gradients of capillarization in the subendocardium of rat heart septum. PMID- 1288174 TI - Oxygen pressure histograms calculated in a block of rat heart tissue. PMID- 1288175 TI - The effect of realistic geometry of capillary networks on tissue PO2 in hypertrophied rat heart. PMID- 1288176 TI - Contractile dysfunction of "reperfused" neonatal rat heart cells: a model for studying "myocardial stunning" at the cellular level? PMID- 1288177 TI - Spatial distribution of oxygen supply units in heart and skeletal muscle and their regulatory significance. PMID- 1288178 TI - Effects of CPPV, PC-IRV, and LFPPV-ECCO2R on right ventricular functions in pigs with ARDS. PMID- 1288179 TI - Factors that determine the oxygen supply of the cell and their possible disruption. PMID- 1288180 TI - Oxygen supply by perfusion and diffusion in heterogeneous tissue models. PMID- 1288181 TI - In situ determination of convection and diffusion profiles in heterogeneous media. PMID- 1288182 TI - Tissue alterations by the penetration of a pO2 sensing needle probe. PMID- 1288183 TI - A new program to evaluate data of pO2 histograph on personal computers under MS DOS. PMID- 1288184 TI - A placental perfusion pO2 logger. PMID- 1288185 TI - A method for simultaneous recording of tissue PO2 and EP in the brain cortex of a test animal with a single electrode. PMID- 1288186 TI - Computer simulation of erythrocyte transit in the cerebrocortical capillary network. AB - The relationship between erythrocyte flow path length and transit time was studied using a probabilistic computer simulation of erythrocyte transit in morphometrically reconstructed cerebrocortical microvascular network of the rat. The results suggest (1) a near-cubic relationship between erythrocyte flow and vessel diameter, (2) preferential pathways of erythrocyte flow, (3) an exponential relationship between erythrocyte transit time and flow path length. PMID- 1288187 TI - Instrumentation and technology for multiparametric mapping of intraparenchymal circulation in the brain cortex. PMID- 1288188 TI - Classification of oxygen transport to tissue with neural networks. AB - In the current stage of the development of the EMPHO II it was shown that the transport of oxygen to tissue can be classified for all applications in real time by using neural networks. The resolution of the oxygen classification is 1%. The implementation of the neural network is possible on a commercial signal processor TMS 320C30 board which is compatible with an IBM PC. The implementation of the neural network is done fully in software and no special neurocomputer is necessary. The results are very promising so that the neural network design goals will be established in the future. In the future further efforts will be made in order to increase the data base and to train the network in more detail. PMID- 1288189 TI - Oxygenation of the cortex of the brain of cats during occlusion of the middle cerebral artery and reperfusion. PMID- 1288191 TI - The oxygen molecule and its course from air to cell. PMID- 1288190 TI - Active and basal whole brain blood flow, oxygen and glucose metabolism in monkeys. PMID- 1288192 TI - The regional cerebral blood flow response to cortical microelectrode insertion is neutrophil dependent. PMID- 1288193 TI - Cerebral blood flow and brain mitochondrial redox state responses to various perturbations in gerbils. PMID- 1288194 TI - Local tissue PO2 during and after focal brain cortical infarction in rabbits. PMID- 1288195 TI - Brain surface pO2 and rCBF in rabbits with a focal cerebral lesion and pulmonary hypoxia under fentanyl-, isoflurane- or thiopental-anesthesia. PMID- 1288196 TI - Treatment of hemorrhagic hypotension with hypertonic saline/dextran: effects on brain surface oxygen tension in experimentally traumatized brain. PMID- 1288197 TI - Monitoring of cortical intracapillary hemoglobin oxygenation in patients during brain surgery--first results. PMID- 1288198 TI - Inert gas washout measurement of muscle blood flow distribution--roles of hypoxia and diffusion limitation. PMID- 1288199 TI - Adaptation of O2 transport and utilization at altitude in man. AB - All stages of the O2 transport pathway are affected in some way by both acute and chronic altitude exposure. At any one stage, the effects are multiple, sometimes subtle, and frequently opposing. Clear-cut differences in responses to acute and to chronic altitude exposure are detectable but not in every case explainable, leaving important and perplexing problems still to be solved. Perhaps the most interesting of these relate to control of cardiac output and to determinants of O2 diffusion from muscle capillary red cells to the muscle mitochondria. PMID- 1288201 TI - Skeletal muscle capillary flow and oxygenation in hypoxic hypoxia: effect of a 5 HT2 receptor antagonist. PMID- 1288200 TI - Effects of endotoxin on canine skeletal muscle oxygen delivery-uptake relations during progressive hypoxic hypoxia. PMID- 1288202 TI - Distribution pattern of capillary and venular red blood cell velocity following ischemia-reperfusion in striated muscle. AB - Ischemia-reperfusion induced changes in distribution pattern of RBC-velocity of nutritive capillaries and postcapillary venules was analyzed in striated muscle using intravital fluorescence microscopy in awake hamsters. Four hours of ischemia to striated muscle contained in the dorsal skinfold preparation (n = 10) revealed a significant (p < 0.01) decrease of capillary, but only a slight decrease of mean venular RBC-velocity during the entire reperfusion period. However, analysis of distribution pattern of single values revealed a shift of the histograms to the left, including pronounced skewness as mean values approached zero. This characteristic phenomenon may be due to an increase of microvascular hematocrit and/or decrease in deformability of red blood cells during ischemia-reperfusion. Beside other factors, the impairment of flow properties and flow conditions of the blood may contribute to the development of microvascular reperfusion injury. PMID- 1288203 TI - Oxygen consumption of human skeletal muscle by near infrared spectroscopy during tourniquet-induced ischemia in maximal voluntary contraction. PMID- 1288204 TI - Tissue oxygenation measurement: a directly applied Clark-type electrode in muscle tissue. PMID- 1288205 TI - Oxygen tension and blood flow in the retina of normal and diabetic rats. AB - The use of microelectrode techniques for studying oxygen distribution and blood flow in the eye of a physiologically well maintained rat provides a very convenient model in which to study oxygen supply to the retina. The availability of rat models of vascular disease such as diabetes and hypertension, and the existence of several models of retinal degeneration, make studies of oxygen supply in the rat eye of particular relevance. The experiments reported in this paper demonstrate changes in oxygen distribution and blood flow very early in STZ induced diabetes. Thus, we have established a preparation in which the role of changes in oxygen supply can be correlated with the pathological events that are apparent later in the disease. PMID- 1288206 TI - Arteriolar spasm and ischemia in the ocular fundus of NaCl-loaded salt sensitive Dahl rats: vascular protection by long-term treatment with the calcium antagonist nitrendipine. PMID- 1288207 TI - Role of arachidonic acid metabolites in pulmonary oxygen toxicity. PMID- 1288208 TI - The relationships between oxygen delivery and consumption and continuous mixed venous oximetry are predictive parameters in septic shock. PMID- 1288209 TI - Oxygen delivery and postoperative mortality. PMID- 1288210 TI - Is oxygen consumption measurement during anesthesia for liver transplantation valuable for a rapid assessment of adequate function of the graft? PMID- 1288211 TI - Assessment of cerebral oxygenation and hemodynamics by near infrared spectrophotometry during induction of ECMO: preliminary results. The ECMO Research Group. PMID- 1288212 TI - Oxygen uptake and static lung compliance during automatic ventilation. AB - Oxygen uptake is an important parameter to control proper tissue oxygen delivery. Oxygen uptake is dependent on adequate lung function and easily disturbed by changes in lung compliance and related parameters such as the tidal volume controlling pressure support. Simultaneous on-line registration of oxygen uptake and lung compliance together with ventilatory pressures applied to achieve preset tidal volumes has been made possible using the computer feedback controlled closed circuit ventilatory system Physio-Flex (Physio Co, Hoofdorp, The Netherlands). The system guarantees for leakage free functioning (maximal leakage 7 mL gas loss/minute) and, therefore, patient oxygen consumption measurements with an accuracy of more than 95%. A specially developed membrane ventilation mode registers on-line flow and displaced volume automatically corrected for temperature, pressure and compressible volume. The current investigation has shown: Decrease oxygen consumption versus oxygen delivery supply dependency may be induced by reflectory decreases of heart rate and cardiac output; in this case a reactive pulmonary parameter change is preceding the event in form of a drop in compliance and corresponding changes in ventilatory pressures necessary to maintain the preset tidal volume. In contrast, decrease of oxygen uptake following changes in cardiac output due to acute hypovolemia has no effect on pulmonary function parameters. This can be diagnostically used as moderate changes of tidal volume also have no significant influence on pulmonary parameters. However, changes due to reduction in depth of anesthesia and relaxation have some influence and need to be excluded. PMID- 1288213 TI - Oxygen uptake/supply dependency in human sepsis: does it increase the risk of multisystem organ failure? PMID- 1288214 TI - Intra-anesthetic on-line monitoring of oxygen consumption using a closed circuit system. PMID- 1288215 TI - pO2-profiles in human muscle tissue as indicator of therapeutical effect in septic shock patients. AB - Automatically stepwise driven pO2 electrodes were transcutaneously inserted into muscle tissue of severely ill septic shock patients. The pO2 profile was plotted from 200 individual measurements registered during 5 minutes and a histogram plotted for documentation. Arterial and venous blood gases, cardiac output, systemic and pulmonary vascular resistance were measured continuously on-line. In septicemia multiple drug schemes are suggested all intending to increase oxygen supply to the tissue and to improve oxygen demand/supply mismatch. So far the attending physician is bound to conclude and continue respectively change the treatment scheme according to the above described macrophysiological parameters. Perfusion distribution and local inhomogenities of tissue oxygen supply remain undetected. In the described study pretreatment pO2 profiles in musculus quadriceps femoris were obtained and measurements repeated in intervals of 10 minutes after start of pharmacological treatment. The changes of pO2 profiles of 20 patients, monitored in such a way over days and weeks, were carefully correlated to the described cardiocirculatory parameters and blood gas analyses. Dopamine was used to improve cardiac function and tissue oxygen supply as well. The investigations show that resulting changes of cardiovascular and blood gas parameters do not always indicate that tissue oxygen supply has really improved. On the other hand there was never an improvement in tissue oxygen supply when no changes of the other parameters had occurred. It is advised to add as a further diagnostic parameter tissue pO2 measurements to get insight if improvement in cardiac and pulmonary function really has the intended effect of improvement of tissue oxygen supply. PMID- 1288216 TI - Preoperative gastrocnemius muscle pO2 as predictor of healing after below knee amputation. PMID- 1288217 TI - Changes of tissue pO2 in the lower leg muscles after vascular surgery. PMID- 1288218 TI - Comparison of different modes of artificial ventilation with extracorporeal CO2 elimination on gas exchange in an animal model of acute respiratory failure. PMID- 1288219 TI - Evaluation of oxygenation with different modes of ventilation in patients with adult respiratory distress syndrome. PMID- 1288220 TI - Hyperbaric oxygen therapy: past, present and future indications. PMID- 1288221 TI - [ESWL treatment of urinary stones at an outpatient clinic]. AB - A total of 107 patients (age: mean 51.6, range 17-85, sex: male 71, female 36) with urinary stones in 112 renoureteral units were subjected to extracorporeal shockwave lithotripsy (ESWL) in situ using an EDAP LT-01 at an outpatient clinic between June 1990 and July 1991. All patients were given an analgesic suppository before ESWL. One ESWL session required 20-60 minutes with a repetition rate of 1.25 Hz, 2.5 Hz or 5 Hz. The effectiveness of the treatment was evaluated in 94 cases consisting of 50 renal units (R1 2, R2 46, R3 2) and 44 ureteral units (U1 16, U2 1, U3 27) three months after the final session according to the criteria reported by Sonoda. Of the 94 cases, 80 cases (85.1%) were stone free and 12 cases (12.8%) had residual fragments of less than 4 mm in diameter. Macroscopic hematuria was seen in all cases. Fever or colicky pain occurred in 3 cases. Outpatient ESWL using the EDAP LT-01 is considered to be safe and efficient for the initial treatment of urinary stones. PMID- 1288222 TI - [Clinical analysis of urolithiasis in Poh Ai Hospital of I-Lan, Taiwan, R.O.C.--a comparative study with urolithiasis in Japan]. AB - Between August 1987 and December 1990, 546 patients were admitted to the department of Urology at the Poh Ai Hospital of I-Lan, Taiwan, R.O.C. for the treatment of urinary stones. These urinary stone cases accounted for 50 to 60% of all urology patients admitted. The incidence of urolithiasis in I-Lan was estimated at 147/100,000 population in 1990. There were 402 male patients and 144 female patients, The male to female ratio was 2.8: 1. There were 450 upper urinary tract stones (kidney, ureter) in 314 males and 136 females, and 79 lower urinary tract stones (bladder, urethra) in 72 males and 7 females. The ratio of upper to lower urinary tract stones was 6:1. Endourological treatments such as percutaneous nephrolithotripsy and transurethral ureterolithotripsy have increased rapidly in recent years. A summary of the present analysis for composition of 365 stones follows. The most frequent type was calcium-containing stone (92.3%), followed by infection stone (4.7%), then uric acid (UA) stone (3.0%). There were no UA stones found in the female patients. According to urinalysis criteria of more than 10 WBC/HPF (x 400), pyuria was found in 67 cases of 334 metabolic stones (20.1%), and 11 cases of 17 infection stones (67.7%). There were neither pediatric case of stone formation nor cystine stones. PMID- 1288223 TI - [Immunological study of interferon-gamma therapy for advanced renal cell carcinoma]. AB - Immunologic and anti-tumor effects of interferon-gamma were studied in six patients with advanced renal cell carcinoma. A daily dose of 10 x 10(6) JRU/m2 of interferon-gamma (IFN-gamma) was given consecutively for five days and the treatment reiterated nine days later. Then the same dose was given every two days for three times and this regimen was also reiterated nine days later. Peripheral blood lymphocytes were analyzed before and one, three, five and eight weeks after the initial administration of IFN-gamma. Although the total number of lymphocytes and monocytes were not changed, CD8 (23.4 to 31.2%, p < 0.05), CD16 (12.4 to 19.3%, p < 0.01) and LeuHLA-DR (29.0 to 39.5%, p < 0.01) positive lymphocytes were significantly increased after the therapy. Non-induced LAK activity (0.6 to 10.8%, p < 0.05) and serum neopterin (3.5 to 10.8 nmol/L, p < 0.01) were also increased. These immunological parameters drastically changed during the consecutive administration of IFN-gamma, and tended to return to the previous value after this period. However, tumor regression was not clinically obtained. Our findings indicate that interferon-gamma stimulated the anti-tumor activity of the host, and administration of IFN-gamma is thought to be of immunological significance even in the advanced high stage cases. PMID- 1288224 TI - [Clinical significance of stereological estimation of mean nuclear volume in human bladder carcinoma--further analysis of nuclear morphometric variables]. AB - Recently, nuclear morphometry methods have been used to quantitatively analyze the malignant potential of cancer cells. We have previously shown that the malignant potential of human bladder carcinoma can be analyzed quantitatively through mean nuclear volume measurements. In the present study, we examined other measurements obtained from nuclear morphometry and evaluated their usefulness as indicators of the outcome of bladder carcinoma. Our subject group consisted of 161 patients with untreated bladder carcinoma. Four nuclear morphometric values were measured on each subject: the mean nuclear volume (MNV), the mean nuclear area (MNA), the nuclear roundness factor (NRF) and the variation of nuclear area (VNA). MNV, MNA and VNA values increased as the tumors progressed to a more advanced stage and grade of malignancy. Patients were then divided into two subgroups based on each morphometric value: small MNV (< 186.9 microns3) and large MNV (> or = 186.9 microns3); small MNA (< 33.6 microns2) and large MNA (> or = 33.6 microns2); low NRF (< 81.1) and high NRF (> or = 81.1); and low VNA (< 33.0) and high VNA (> or = 33.0). Survival rates were significantly higher among patients with a small MNV, a small MNA and a low NRF (5-year survival rate; 93.0, 84.9 and 84.6%), compared to patients exhibiting high values (5-year survival rate; 59.7, 61.3 and 61.9%). For patients with grade 2 tumors, those with a small MNV had a high survival rate (5-year survival rate; 95.2%), similar to that of patients with grade 1 tumors (5-year survival rate; 95.2%)(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288225 TI - [The role of urodynamic study in female patients with urinary incontinence]. AB - To determine the type of urinary incontinence in 96 female incontinent patients, we performed a comparative study between the clinical evaluation and the results of urodynamic studies. Their complaints, physical examination, laboratory examinations including routine urological X-ray and ultrasonic studies, revealed that 15 to 30% of the patients had another type of incontinence than those with stress incontinence, urge incontinence and those in whom diagnosis was made from urodynamic studies. Urodynamic studies disclosed that another urinary incontinence type was observed in 7 to 18% of the patients, who were not improved in spite of treatment which was required because of their complaints and physical examination. Our findings showed that urinary incontinence could not be classified according to the frequency of urination or vesical volume. Urodynamic studies may be essential in female patients with urinary incontinence scheduled to have an operation or for whom initial treatment was unsuccessful. PMID- 1288226 TI - [Subcapsular orchiectomy using the ultrasonic surgical aspirator in patients with advanced prostatic cancer]. AB - We report a technique for performing subcapsular orchiectomy using the ultrasonic surgical aspirator (USA). The procedure was simple and safe, and was completed within one hour in 2 patients on whom it was carried out. Operative complications such as bleeding, postoperative pain and wound swelling were minimal, and compression dressings were not necessary. Postoperatively, the serum testosterone value was lowered to the castrate level. We conclude that subcapsular orchiectomy using USA is superior to conventional bilateral scrotal orchiectomy, and will be a useful option. PMID- 1288227 TI - [Solitary infected renal cyst: a case report]. AB - A 48-year-old man was admitted to our hospital because of high fever and left flank pain. Laboratory findings revealed a high white blood cell count, high C reactive protein level, and severe pyuria. Sonographic examination revealed an enlargement of the cyst at the upper pole of the left kidney that had already been detected. Percutaneous drainage was performed for the cyst and 60 ml of purulent fluid was obtained. Bacterial culture of the fluid was positive for Propionibacterium acnes and gamma-Streptococcus. The drainage and administration of povidone-iodine was continued for 7 days. The size of the cyst was reduced with disappearance of symptoms. PMID- 1288228 TI - [Esophago-bronchial fistula caused by chemotherapy with bronchial artery infusion for pulmonary metastases from urinary tract cancer]. AB - We treated a patient who had had postchemotherapeutic pulmonary metastases from urinary tract cancer by bronchial artery infusion (BAI) chemotherapy. Pulmonary lesions showed a 33.0% reduction after the treatment. However, esophago-bronchial fistula (EBF) occurred after the second BAI. The patient died of recurrent aspiration pneumonia and sepsis in the sequelae of the repair surgery. The fistula was considered to have resulted from an increase in the blood flow to the esophageal branch originating from the bronchial artery after the first BAI, which had consequently damaged the local tissue due to accumulation of anti cancer drugs. In order to avoid these complications, the secondary change of blood flow should be examined precisely by preceding angiographical mapping, and the concentration and the infusion speed of the cytotoxic drugs, should be under adequate control. PMID- 1288229 TI - [Primary carcinoma in situ of the ureter: a case report]. AB - A 47-year-old man presented with gross hematuria and left lower abdominal dull pain of 6-weeks duration. Cystoscopic examination revealed bloody efflux from the left ureteral orifice but no tumor in the bladder. Retrograde pyelogram showed irregular stricture of middle portion of the left ureter. Cytologic studies of the voided urine and left ureteral urine were positive for cancer, and nephro ureterectomy with excision of a bladder cuff was carried out. The surgical specimen showed no intraluminal mass but histologically, transitional cell carcinoma in situ with G3 anaplasia and squamous metaplasia was found in the narrowed portion of the ureter. Followup examinations, including exfoliative urinary cytology, cystoscopy and IVP revealed no abnormalities until intravesical recurrence was confirmed 34 months later. Transurethral resection of bladder tumor was performed and superficial papillary transitional cell carcinoma with G2 anaplasia was found in the trigone of the bladder. Followup examinations for the last one year have revealed no abnormalities. PMID- 1288230 TI - [Prostatic carcinoma presenting as an abdominal mass: a case report]. AB - Prostatic carcinoma presenting as an abdominal mass is a very rare disorder. A 64 year-old man was referred to our hospital with the chief complaint of a right lower abdominal mass on March 6, 1984. Physical examination revealed a firm, smooth, fixed, non-tender, pulseless fist size mass in the right lower abdomen. Rectal examination revealed an apple size, smooth and elastic firm prostate which had an induration. Needle biopsy of the prostate showed well-differentiated adenocarcinoma. At first we regarded the abdominal mass as retroperitoneal tumor unassociated with prostatic carcinoma. After preoperative irradiation (20 Gy) to the pelvis, the abdominal mass was resected and bilateral orchiectomy was performed on April 11, 1984. The mass was histologically diagnosed as a metastatic lesion from prostatic carcinoma. On the basis of these findings, we considered the mass to be due to pelvic lymph node metastasis from prostatic carcinoma. His postoperative course was uneventful. In April 1991, he is still alive without evidence of recurrence or bone metastasis. PMID- 1288231 TI - [A case of muellerian duct cyst treated with minocycline hydrochloride sclerotherapy under ultrasound control]. AB - We present a case of a muellerian duct cyst in a 55 year-old man. A cystic lesion was incidentally found between the prostate and the bladder on transabdominal ultrasound examination. Computerized tomography revealed a low density area homogeneous and round with a clear margin. Both urethrocystgram and vesiculogram demonstrated no cystic lesion. On diagnosis of muellerian duct cyst percutaneous needle aspiration was performed under ultrasound control. The aspirated fluid was yellow, clear and negative for cytology. Microscopically no spermatozoa were found in it. Minocycline (100 mg) was injected into the cyst. No recurrence has occurred since the operation. The literature of the cyst was briefly reviewed. PMID- 1288232 TI - [Primary adenocarcinoma of the male urethra with high CA125 level: a case report]. AB - A case of primary adenocarcinoma of the male urethra with high CA125 level is reported. A 66-year-old man was admitted to our hospital with dysuria and perineal discomfort. The urethrocystogram revealed an irregular urethral margin in the bulbo-membranous urethra. Computer-tomographic (CT) scan and transrectal ultrasonography revealed an irregular mass between the urethra and rectum. Cytologic examination of the urine was negative for malignancy. Endoscopy revealed an irregular bulbo-membranous urethra with a small papillary lesion. Transurethral biopsy was performed and histological diagnosis was adenocarcinoma. The patient rejected surgical treatment and radiotherapy was performed. However, the disease progressed and the patient died from liver metastasis six months later. We considered that CA125 was valuable as a tumor maker in this patient. PMID- 1288233 TI - [Primary urethral carcinoma in a female: report of a case]. AB - An 74-year-old female patient with urethral carcinoma is reported. A mass at the urethral meatus was seen and diagnosed as transitional cell carcinoma and squamous cell carcinoma by biopsy of the lesion and urine cytology. Total cystectomy and urethrectomy were performed. Adjuvant therapy was not performed, but recurrence has not been seen 36 months after operation. PMID- 1288234 TI - [A case of chronic scrotal hematocele and review of the literature]. AB - A 38-year-old man visited our hospital because of swelling of left scrotal content. He had no history of trauma of scrotum, fever, pain or dysuria. Physical examination revealed a tumor larger than a fist in the left scrotum. Ultrasonography revealed an echogenic mass with echolucent area in the scrotum. Surgical extirpation of the left scrotal tumor was performed under the diagnosis of left testicular tumor. The mass was encapsulated by a white fibrous membrane and was 700 g in weight. The tumor contained 200 ml of dark brown pus-like material. Histological examination revealed deposition of cholesterine crista and infiltration of lymphocyte in tunica vaginalis with extremely atrophic testis, destructive spermatogenesis and atrophic epididymis. Twenty one cases of chronic scrotal hematocele have been reported in the Japanese literature. The age of the patients reported was 38 to 77 years old with a mean age of 65 years. Orchiectomy was done under the diagnosis of testicular tumor in 20 of the 21 cases. Our case was thought to be of an idiopathic chronic scrotal hematocele. The disease should be considered even in the absence of a particular cause such as injury and inflammation of scrotal content. PMID- 1288235 TI - [Thrombosis of the posterior scrotal vein: report of two cases]. AB - A 47-year-old architect and a 30-year-old designer of audio goods presented with thrombosis of left and right posterior scrotal vein, respectively. Both had scrotal masses associated with a feeling of heaviness. Physical, operative and microscopic findings were similar. The lesions were palpated as nontender, slender, elastic masses and located parallel to the urethra in the posterior aspect of the scrotum. At surgical exploration the lesions appeared to be thrombosis of posterior scrotal vein and were removed. Both patients have remained well one year in one and four months in the other after operation. Pathological diagnosis for both surgical specimens was organized thrombosis of vein with eosinophilic infiltration. Eosinophilic infiltration to lesions in the present cases and the occupation of patients suggested that some immunological disorders and localized venous stasis for long time during their sitting work might relate to the formation of thrombosis in the posterior scrotal vein. To our knowledge this is the first report of thrombosis of the posterior scrotal vein. PMID- 1288236 TI - [A case of intrascrotal hemangioma]. AB - Intrascrotal hemangioma is rare. A case is presented and the literature is reviewed. A 35 year-old male with the complaint of a painless right scrotal mass underwent right high orchiectomy because the mass was hard and difficult to separate from the right testicle in scrotal exploration. Histologic study revealed that the tumor consisted of a venous hemangioma and the greater part of it was displaced by organized connective tissue. It is extremely rare for a case of intrascrotal hemangioma to require orchiectomy. PMID- 1288237 TI - [Utility of recombinant human erythropoietin on the anemia of elderly hemodialysis patients]. AB - Recombinant human erythropoietin was administered to 59 patients over 65 years of age receiving maintenance hemodialysis treatment in Kyoto and Shiga district, in order to evaluate its utility on renal anemia. After 6 months of administration, the hematocrit rose from 20.8 +/- 3.5% to 28.0 +/- 3.7% with concomitant improvement of subjective symptoms related to anemia. Twelve patients developed side effects, in 10 of whom elevation of blood pressure was observed. We found no clinically significant abnormalities in the laboratory data. In conclusion, recombinant human erythropoietin is highly useful in the treatment of renal anemia in elderly hemodialysis patients. PMID- 1288238 TI - [Prophylactic effect of UFT in combination with intravesical chemotherapy on the recurrence of superficial bladder tumor]. AB - The influence of N1-(2-tetrahydrofuryl)-5-fluorouracil plus uracil (UFT) on the recurrence of superficial bladder tumors was evaluated in a randomized clinical study. Group A (n = 196) underwent transurethral resection (TUR) and the intravesical chemoprophylaxis, while group B (n = 193) received 400 mg per a day of UFT orally for 6 months in addition to the instillation therapy. These adjuvant therapy was started one week after TUR. Consequently, 30 patients in group B showed UFT-related toxicity and administration of UFT was discontinued in 10 of them. In addition, 87 patients in group B did not complete the 6-month course of UFT administration. Comparison of 2-year actuarial non-recurrence curves revealed no significant difference between groups A and B. However, UFT seemed to have a favorable prophylactic effect when recurrence rates were compared among those patients with recurrent tumors (generalized Wilcoxon: p = 0.1277), and those with recurrent multiple tumors (p = 0.0847). PMID- 1288239 TI - [Clinical application of Dornier Lithotripter Compact for upper urinary tract stones]. AB - The results of clinical application of a Dornier Lithotripter Compact (Dornier Medical Systems Co., Ltd.) on upper urinary tract stones are presented. Between October 1991 and June 1992, 30 patients with upper urinary tract stones were treated with ESWL in the Department of Urology, Kyoto University. Although 49 sessions for 32 stones in total were carried out without anesthesia, analgesics such as indomethacin and/or pentazocine were required in 37 sessions (76%). Stone free rate 3 months after the last session was 12/30 cases (40%) and the success rate, the ratio of the patients without residual stone or with residual stones less than 4 mm to total 30 patients, was 18/30 (60%) at the point. Macrohematuria was seen after the treatment in 42/49 (86%) sessions, but it disappeared within 3 days in all instances. Pain necessitating analgesics after the treatment was seen in 16/49 (33%) sessions. Subcutaneous bleeding and fever-up of less than 38 degrees C were seen in 15/49 (31%) and 8/49 (16%) sessions, respectively, but bacteremia after the treatment was not detected in any case. No serious adverse effects were observed in blood chemistry. The Dornier Lithotripter Compact is considered to be useful in the treatment of renal and upper third ureteral stones. PMID- 1288240 TI - Tropical nephropathy--an overview. PMID- 1288241 TI - A prospective study on some factors which influence the delivery of low birth weight babies in a developing country. AB - The study was prospective in design and carried out in Ibadan, Nigeria. It was undertaken in order to provide more information on the low birth weight deliveries seen here and to evaluate some factors associated with their births. 600 randomly selected gravid women who presented to the antenatal booking clinics for the first time in this pregnancy were followed up till delivery of their babies. Data on 492 women who produced normal, singleton babies were analysed. The mean birth weight was 3167g +/- 451g (males; 3205g +/- 469g and significantly higher than of females of 2991g +/- 468g). The incidence of low birth weight (LBW) weight of 2500g and less was 8.3% and comprised of 18 males, 22 females and 1 unknown sex. 80% of these LBW babies were term (37-41 wks gestation) at delivery, while 20% were pre-term (< 37 wks). There was seasonal variation in the incidence of LBW, the risk being highest during the peak of dry season and lowest during the rainy season. The mothers age, parity, height, ponderal index at delivery, and total maternal weight gain as well as birth interval were each significantly related to the incidence of LBW in these mothers (P < 0.01). Maternal education as well as socio-economic class were not significant (P > 0.5). PMID- 1288242 TI - Student's attitude and predictor of performance in anatomy. AB - A survey of the attitude and performance of 158 students, made up of 101 males and 57 females that undertook second year anatomy examination in Obafemi Awolowo University, Ile-Ife, Nigeria was conducted. The results showed that there was no significant difference in the performance of the male and female students (P > 0.05); that age, performance at the Joint Matriculation Examination (JME), grade point average (GPA) in first year in the University, and performance in practical anatomy dissection had significant positive correlation with performance at second year examination in anatomy (PA2) (P < 0.05). However, Chi-squared test showed that hours spent on private students, JME score, have no significant association with PA2 (P > 0.05), but GPA has significant association with PA2 (P > 0.05). This suggests that GPA in the first year in the University is a predictor of performance in year two anatomy. PMID- 1288244 TI - The prevalence of hepatitis B surface antigen in the Gezira (Sudan). AB - The prevalence of hepatitis B surface antigen (HBsAg) was studied in blood donors and laboratory technical staff from the Gezira area in Sudan. Of a total of 110 donors, 19 (17.3%) were found to be carriers of the antigen and 4 of 33 (12.1%) technical staff were also found to be carriers. Routine testing of blood donors is recommended as a way of reducing the incidence of post-transfusion hepatitis in the Gezira area of Sudan. PMID- 1288243 TI - The development of the cerebral mantle in the mouse embryo after brief in utero hyperthermic stress. AB - The width of the different layers of the cerebral mantle of 16-day mouse embryos was measured after exposure of pregnant dams to a hyperthermic stress of 43 degrees C for 10 minutes in a laboratory oven, during the period of neural tube closure. The dams were exposed on day 7 1/2 or 8 1/2 post coitum. A control group of mice was placed in the oven at ambient temperature (28 degrees C) for 10 minutes. At 43 degrees C oven temperature, the core temperature of the pregnant dams was elevated by 2-3 degrees C (P < or = 0.001). In non-pregnant mice, this degree of heat stress results in a sustained hyperthermia of about six minutes and a return to normal temperature 15 minutes after removal from the oven. There were no congenital malformations of the central nervous system. The mean litter sizes, percentage resorptions and fixed embryonic weights were similar in the experimental and control groups. The width of the cortical plate was significantly reduced in all the regions measured (P < or = 0.001). The width of the matrix layer was reduced only in the fronto-parietal region. The results suggest that this sub-teratogenic dose of hyperthermic stress reduces neuronal population in the cerebral cortex. This may be the structural substrate for the impairment of function in animals heat stressed during prenatal development. PMID- 1288245 TI - Translaryngeal guided intubation in a patient with raised intracranial pressure. AB - A 60-year old man with intracranial space occupying lesion, presented with difficulty in intubation at induction of anaesthesia. Several attempts at direct tracheal intubation were made until the airway was finally secured. Though the brain was slack, the tumour could not be located at this operation. He presented for re-operation with worse signs of raised intracranial pressure which may accompany repeated attempts at intubation, a planned translaryngeal guided intubation was employed to secure the airway. Where fibreoptic laryngoscope is unavailable and difficult tracheal intubation is envisaged, translaryngeal guided intubation may save time and reduce morbidity of prolonged and repeated attempts at tracheal intubation. PMID- 1288246 TI - Pattern of adrenocortical response to the stress of severe illness in Nigerians. AB - Twenty-eight severely ill, hospitalized Nigerian patients, 18 males and 10 females with a median age of 41 years (group I) and 20 stable ambulatory patients, 11 males and 9 females with a median age of 42.5 years (group II), had early morning plasma cortisol measurements. Ten healthy young Nigerian males with a mean age of 22.1 years (group III) had plasma cortisol estimations during insulin tolerance test. The mean (+/- SD) cortisol values for the three groups in nmols/l were as follows: group I--389.3 (202.4), group II--267.1 (67.4), group III-624.5 (81.1). The results for the group III healthy controls represent the peak (60 mins) value during insulin induced hypoglycemic stress. A one way analysis of variance (ANOVA) demonstrated a statistically significant difference between the three mean cortisol values, P < 0.001. A pair-wise comparison using the t-test also showed significant differences between the groups, P < 0.05 in each case. An important observation was the variable pattern of cortisol stress response in different types of illnesses. Cases of stroke appeared to be associated with increased cortisol stress values (Z-score + 5.67) while patients with hypotension (B.P. < or = 90/60) and those on Rifampicin had reduced cortisol responses (Z-scores - 3.66 and 3.51 respectively). However, no firm recommendations can as yet be made regarding the usefulness of corticosteroids in life-threatening illnesses among Nigerians, other than those for which steroids are known to beneficial. PMID- 1288247 TI - Cross reactivity between Klebsiella pneumoniae and ocular tissue. AB - Klebsiella pneumoniae has been implicated as a possible aetiological agent in ankylosing spondylitis and acute anterior uveitis. Cross-reactivity between antigens of klebsiella and bovine vitreous has been reported. In the present study sera from rabbits immunised with Klebsiella pneumoniae was tested against fresh guinea pig and human ocular tissues using immunodiffusion and immunofluorescent methods. No cross-reactivity between klebsiella and the ocular tissues used could be demonstrated by these techniques. PMID- 1288248 TI - Socio-economic class distribution of the prognostic variants of lymphoproliferative cancers in Nigerians. AB - One hundred and twenty Nigerians with various lymphoproliferative cancers were grouped according to socio-economic class and the prognosis of their disease. The best prognostic variant of acute lymphoblastic leukaemia occurred mainly in the highest socio-economic class and the worst variant mostly in the low socio economic class. Chronic lymphocytic leukaemia, a low grade malignancy, and the high grade Burkitt's type of Non-Hodgkin's lymphoma occurred predominantly in the low class. The relationship between prognosis and socio-economic class was not so remarkable in patients with Hodgkin's disease and multiple myeloma. The precise mechanisms by which socio-economic strata influence development of the different prognostic variants of individual lymphoproliferative cancers are not certain. PMID- 1288249 TI - An evaluation of adi agbon as a clearing agent in paraffin processing of embryonic tissues--preliminary report. AB - Adi agbon, an oily extract of the endosperm of the coconut fruit (Cocoa nucifera, L.) was investigated as a clearing agent for embryonic soft tissues. Paraffin sections stained with haematoxylin an eosin revealed normal tissue architecture and light microscopic details were easily identified. However, some tissue shrinkage was observed, particularly in the brain. As prepared for this study, this locally available compound is useful for routine work but appears unsuitable for quantitative histological studies. PMID- 1288250 TI - Medical education, healthcare and development in Africa. PMID- 1288252 TI - Benign Familial Neonatal Seizures. AB - Benign Familial Neonatal Seizures (BFNS) occur in normal newborns without perinatal neurological damage or metabolic abnormalities in the setting of a positive family history for neonatal seizures. This autosomal dominant disorder has an excellent prognosis, in contrast to most other causes of neonatal convulsions. This paper points out the need to include BFNS in the differential diagnosis of neonatal seizures and to specifically seek a family history to avoid an unnecessarily extensive diagnostic evaluation and poor prognostication. We present a family with one atypical and three classic cases. Further study of BFNS may reveal more definitive basic science information leading to the inclusion of variant forms into the currently narrow clinical definition. PMID- 1288251 TI - The causes and course of acute tubular necrosis in Nigerians. AB - To characterize the precipitating factors and course of acute tubular necrosis (ATN) in Nigerians, we studied the clinical course of ATN in 40 consecutive patients (22 male) seen in the Renal Unit of the University College Hospital, Ibadan, between June 1986 and July 1989. Nephrotoxicity resulting from the use of traditional herbal remedies (15 patients, (37.5%)) and septicaemia (7 patients (17.5%)) were the most commonly identified precipitating factors. The mean duration of the oliguric phase was 9 +/- 3.8 days, while that of the diuretic phase was 17.5 +/- 7.1 days. Majority (26 patients (65%)) were anuric at presentation. The mean urine output during the oliguric phase was 16.7 +/- 36.5 ml, whereas it was 3622 +/- 2159 ml during the diuretic phase. Transient hypertension occurred in 8.5% of cases. A total of 10 patients (25%) died. Six deaths occurred in non-dialysed patients while 5 were associated with encephalopathy. Of the 15 patients in whom ATN resulted from the use of herbal remedies, only 1 died. Nephrotoxicity from traditional herbal remedies is an important cause of ATN in Ibadan. The exact pathogenesis is unclear and warrants further investigation. PMID- 1288253 TI - Characteristics of firearms and gunshot wounds as markers of suicide. AB - Data from a total of 1,200 cases that the Medical Examiner of Dallas County, Texas, ruled as suicide with a firearm have been compared with the results of forensic laboratory examinations and tests; 75% are with handguns and 25% are with long guns. The incidence of suicides by gender yields 82% males and 18% females, with the most common entrance site being the head. With regard to racial distribution of persons committing suicide, > 88% are white in the study population group, which is 76% white. Data are presented for the incidence of blood detected inside and on the muzzle end of the barrel of the firearm, and for the persistence of blood inside the barrel even after the weapon was discharged to obtain test bullets. The analysis of handwipings for primer residues shows that "positive" results are obtained for approximately 50% of the revolvers and approximately 32% of the pistols when the caliber is > 22. Other projects such as transfer of gunshot residues to the hand by simply handling the weapon, the incidence of single-contact wounds in homicide versus suicide cases, and the percent of positive identification of bullets with weapons submitted are described. PMID- 1288254 TI - The effects of various intermediate targets on dispersion of shotgun patterns. AB - Intermediate targets cause dispersion of a shot pattern by a ricochet effect. Thus, the intermediate target must have sufficient thickness or tensile strength to slow down the initial group of shot striking the target. Aluminum and steel screen, ordinary window glass, thin cardboard and thin cowhide did not manifest these qualities under the conditions of these experiments. PMID- 1288255 TI - Wounds caused by contact with muzzle-lift relief ports (Mag-Na-Port). AB - Fan-shaped stippled burns were produced on the skin when a revolver whose barrel had been modified by the Mag-Na-Port process was fired twice with the side of the muzzle in contact. A grazing wound was produced by one bullet, and an oblique entry was produced by the other. The characteristics of Mag-Na-Port wounds and test shots are described, and these are compared with test shots from two other higher power revolvers. PMID- 1288256 TI - Renal artery bullet embolism. AB - Bullet embolism is a well-recognized phenomenon. While bullet embolism is not common, renal artery bullet embolism appears to be very rare. We report three cases of bullet embolism to a renal artery. Autopsy findings and bullet types are presented. Such cases are of particular interest to both the medical examiner and the clinician. Failure to consider this phenomenon clinically could lead to infarction of a kidney. A consideration of this phenomenon at autopsy could shorten the dissection time required to retrieve the bullet. PMID- 1288257 TI - So-called accidental firearm fatalities in children and teenagers in Tennessee, 1961-1988. AB - Tennessee State medical examiner reports of firearm fatalities classified as accidents involving victims aged 19 year or less from 1961 through 1988, were reviewed to evaluate circumstantial and contributing factors. A total of 225 were analyzed. The peak age for victims was 17 years, and there were more than five times more male than female victims. In Shelby County (Memphis), the racial distribution of fatalities was approximately that of the general population. Playing with a gun was the most frequent circumstance. The person responsible for pulling the trigger was equally likely to be a friend, a family member, or the victim. Head or neck were injured in most cases. The urban mortality rate was nearly twice that of the rural rate. More than half of the deaths in urban counties occurred indoors and involved handguns, whereas in rural counties only a third were due to handguns and the location was more often outdoors. Deaths in rural counties showed a seasonal variation that corresponded with the hunting season; by contrast, a peak in early summer was noted in the urban deaths. Defective guns or guns unsafe in design caused several deaths. (Semiautomatic pistols, which can be fired after unloading the ammunition magazine, are conspicuous examples of guns unsafe in design.) An important observation of this study is that medical examiners vary considerably in their classification of accidental manner, particularly when children are involved. Furthermore, medical examiner reports need to include much more information than is currently recorded if they are to be useful in guiding public policy to reduce firearm injuries. PMID- 1288258 TI - The rebirth and blooming of forensic medicine, Milton Helpern Lecture. AB - This features a presentation by Dr. Sidney Kaye on the occasion of the Milton Helpern Lecture at the annual meeting of the National Association of Medical Examiners near Fort Myers in Florida in 1989. The author experienced the "golden age" of forensic medicine as a student and associate of Dr. Alexander Gettler in the New York Medical Examiner's Office. He also worked with Dr. Rutherford Gradwohl in the St. Louis Police Department and was one of the founders of the American Academy of Forensic Sciences. He was the toxicologist in the Virginia medical examiners' system before moving to Puerto Rico. His discussion is a historical review of his experiences in developing forensic sciences. PMID- 1288259 TI - Death due to attack from chow dog. AB - It is estimated that between one and four million persons per year are bitten by dogs in the United States. While most injuries associated with the bites are minor, serious sequelae, and even death, may occur. Most victims of fatal dog attacks are children < 1 year of age or elderly women. The most frequent cause of death is hemorrhage and shock from major vessel damage. A case is reported in which an elderly woman was attacked by her pet Chow dog. The victim received multiple superficial abrasions, contusions, and lacerations from the dog attack. A large perforation of the right external pudendal vein and three perforations of the left superficial femoral vein resulted in exsanguination and death. Fractures of the left 2nd through 4th ribs with underlying pulmonary contusion were also found. PMID- 1288260 TI - Visual identification from videotape after electronic erasure of mutilating injuries. AB - A rapid method of identification by using computerized videotape erasure of mutilating injuries is presented. The identification of a human head, which was mutilated and severed in two major fragments, illustrates the application of the method. Following the reconstruction and suturing of the head fragments, the face was videotaped and the mutilating injuries were electronically erased. The televised broadcasting, in color, of the reconstructed face, free of injuries, elicited prompt visual identification by relatives of the deceased within < 1 h. PMID- 1288261 TI - Life masks and death masks. AB - The death of a relative or anyone in a small, tightly knit community with closely shared cultural and religious values has great social impact. As part of the grieving process, people wish to preserve the memory of a loved one or a community leader. Life masks and death masks have been used as art forms to mark life passages, offering permanent reminders of family and continuity with the past. This article discusses the history and technique of life and death masks and their role in 19th-century American culture. PMID- 1288263 TI - Failure of thumbtacks used in control of presacral hemorrhage. AB - We report a case of failure of thumbtacks used in achieving last-resort hemostasis in a gunshot injury to the presacral venous plexus/sacrum. Four of five thumbtacks used detached. The exact mechanism of failure is not known. To our knowledge, there are no reports of failure of these hemostatic devices in the literature. This finding suggests to us that thumbtack hemostasis is not without complication. It is not known whether injury to internal viscera and organs occurred secondary to the loose thumbtacks. We suggest that surgeons as well as pathologists use caution when exploring pelvic or abdominal cavities following pelvic vascular trauma due to the considerable danger posed by these sharp objects. PMID- 1288262 TI - Homicidal manual strangulation and multiple stun-gun injuries. AB - Stun guns are electric shock devices that are used by a number of law enforcement agencies to subdue violent offenders, but sometimes are discharged into human bodies as offensive weapons. We autopsied a 22-year-old woman who was strangled and had many stun-gun injuries on her head, chest, abdomen, arms, and legs. The stun-gun injuries consisted of many pairs of round erythemas with or without central paleness, some of which were accompanied by circumferential abrasions. To determine whether the electric shocks were administered before or after her death, we studied stun-gun injuries on pigs before and after death and found that the shocks after death did not mark the animal skin. Based on this experiment, all of the stun-gun injuries on the victim's body were concluded to have been inflicted before her death. PMID- 1288264 TI - Fatal hydrothorax associated with subclavian vein catheterization for hemodialysis. AB - A rare iatrogenic complication of subclavian vein catheterization for hemodialysis is massive hydrothorax. A case is presented that illustrates the need for adherence to a standard procedure of prompt roentgenologic examination in conjunction with catheterization, and emphasizes the importance of the autopsy as a means of quality assurance. PMID- 1288265 TI - Fatty liver, encephalopathy, and sudden unexpected death in early childhood due to medium-chain acyl-coenzyme A dehydrogenase deficiency. AB - A case of sudden death associated with fatty liver and encephalopathy is described in a 4-year old white boy with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The death was caused by hypoglycemia triggered by fasting and vomiting associated with a minor viral infection. The differential diagnosis of the hepatoencephalopathy is discussed in relation to other conditions, especially Reye's syndrome. The forensic pathologist should be familiar with MCAD and other deficiencies of beta-oxidation of fatty acids as a cause of sudden unexpected death in children in order to advise parents in genetic counseling to prevent disability or death of other affected, but still asymptomatic siblings. PMID- 1288266 TI - Papillary hyperplasia of the lingual tonsil and sudden death in epilepsy. AB - Papillary hyperplasia of the lingual tonsils is a rare entity not previously reported at autopsy. We report a case that occurred in a 19-year-old man who died suddenly from his epilepsy, associated with aspiration of gastric contents. We describe the pathological features of this unusual condition, discuss the possible significance in this case and stress the importance of routine examination of the tongue and pharynx in every autopsy. PMID- 1288267 TI - An asthmatic death while under Chinese acupuncture and moxibustion treatment. AB - A 29-year-old Japanese man with bronchial asthma died while undergoing Chinese acupuncture and moxibustion treatment. The autopsy findings of the lungs were compatible with a diagnosis of severe asthma. Further, on immunohistochemical examination, hypoxic brain damage and an unusual distribution of pulmonary surfactant were found. In contrast, only minor hemorrhages in the right semispinal muscle and round-shaped bruises were seen as a result of Chinese acupuncture and moxibustion treatment. Thus, it was concluded that the man had died from a severe asthmatic attack. PMID- 1288268 TI - Clinical and pathological findings in fatal plant oxalosis. A review. AB - Poisoning by ingestion of oxalate-containing plants, such as raw rhubarb, is infrequent, and such deaths are rare. We present a review of the most important clinical and pathological aspects of oxalate poisoning and recommend that the public be educated about the dangers of eating unknown plants with potentially adverse effects. PMID- 1288269 TI - Methadone toxicity causing death in ten subjects starting on a methadone maintenance program. AB - Methadone maintenance therapy is designed to reduce the need for addicts to use heroin or other illegal opiates. Death in patients starting on such a program has not previously been documented. We report the death of 10 persons who died within days of starting a methadone maintenance program administered by general practitioners. Their bodies were subject to a full autopsy by forensic pathologists, with a full toxicological examination. The mean starting dose had been 53 mg, which had been increased to a mean of 57 mg by the final dose. Death occurred after a mean of 3 days. The mean blood methadone concentration at death was 2.1 mumol/L. Complete toxicological analysis showed that six subjects had additional drugs present including two with alcohol, two with benzodiazepines and morphine, and one with benzodiazepines alone. Pathological examination revealed the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five. The causes of death were given as methadone toxicity or methadone toxicity in combination with bronchopneumonia. Our observations highlight the dangers of methadone in the first days of starting on a maintenance program, particularly when the starting doses are relatively high and subjects have no demonstrated tolerance to opiates. PMID- 1288270 TI - Toxicological findings in a death involving dextromethorphan and terfenadine. AB - A case of fatal self-poisoning with dextromethorphan, an antitussive, and terfanadine, an antihistamine H1, is reported. Both drugs were quantified in several postmortem tissues and fluids using capillary gas chromatography coupled to mass spectrometry. Results are discussed in the light of the existing literature. PMID- 1288271 TI - Fatal respiration of liquefied petroleum gas. AB - We have found that an efficient method of providing evidence of lethal solvent abuse is to sample headspace above lung tissue and then perform cryogenically focused gas-liquid chromatography. In the case presented, the level of lethal agent in lung tissue was low, but the solvent was present in abundance in the pleural cavity. We conclude that the pleural cavity acts as an efficient trap for aspirated substances. PMID- 1288272 TI - How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach. AB - Largely unexplained increases in breast cancer incidence of about 1% per year have been documented back to the 1940s. Since 1982, breast cancer incidence in women aged 40 years and above has been increasing at a faster rate than this long term secular trend, especially in women aged 60 years and above. Increases in the use of mammography since 1982 (which have been documented in population surveys of women) provide the most plausible explanation for the incidence increase over the long-term secular trend. A study by White et al. (J Natl Cancer Inst 1990;82:1546-52) found that, for women aged 45-64 years, the increase in mammography utilization could explain the incidence increase, while for women aged 65-74 years, it could account for only half the increase. The authors have developed an alternative model to that of White et al. that incorporates estimates of differential lead time (time from screen detection to clinical detection in the absence of screening) by age group. Using this model, the authors show that if older women have longer lead times, than similar increases in mammography utilization across age groups will lead to a larger incidence increase in older women. Thus, the observed increases in mammography utilization are generally concordant with increases in incidence, even in the older age groups. PMID- 1288274 TI - Breast cancer risk factors among black women and white women: similarities and differences. AB - To further explore whether breast cancer risk factors are the same for black women and white women, the authors investigated several biologic, cultural, and social factors in a 1980-1982 case-control study of non-Hispanic black subjects (490 cases, 485 controls) and non-Hispanic white subjects (3,934 cases, 3,901 controls) aged 20-54 years. Logistic regression analyses indicated that blacks and whites shared four risk factors at a comparable magnitude (age at first full term birth, parity, surgical menopause, and history of benign breast disease). For two observed risk factors, the magnitude (breast feeding) and pattern (family history of breast cancer) of the relation were different in blacks and whites. The relative risks of breast cancer among black women who had first-degree relatives (odds ratio (OR) = 1.61) and second-degree relatives (OR = 1.71) with breast cancer were similar, whereas the relative risk among white women who had first-degree relatives (OR = 2.16) was distinctly larger than for those who had second-degree relatives (OR = 1.44) with breast cancer. The relation of early age at menarche appeared negligible for blacks although significant for whites aged 12 and under (OR = 1.26). The results also indicated that natural menopause, oral contraceptive use, and cigarette smoking may have different, and more complex, relations to breast cancer among blacks and whites. PMID- 1288273 TI - A case-control study of the risk of breast cancer in relation to oral contraceptive use. AB - The relation of oral contraceptive use to the risk of breast cancer was evaluated in a case-control study of women under the age of 70 years, conducted in Toronto, Canada, from 1982 through 1986. A total of 607 breast cancer cases identified in a cancer hospital were compared with 1,214 controls matched to the cases on neighborhood and decade of age. Information on oral contraceptive use and risk factors for breast cancer was collected in home interviews. Conditional logistic regression was used to control multiple confounding factors. For women aged 40-69 years (527 cases, 1,054 controls), the results suggest that oral contraceptive use does not increase the risk of breast cancer. Multivariate relative risk estimates were close to or below 1.0 for long durations of use overall and in various categories of parity status and other factors. For women under the age of 40 years, the data were sparse (80 cases, 160 controls). Although there were some elevated relative risk estimates, most were not statistically significant, and there were no consistent patterns across duration of use. The present data add to the body of evidence that indicates that oral contraceptive use does not adversely affect the risk of breast cancer in older women; the data are inadequate to clarify the effect in younger women. PMID- 1288275 TI - Improved ascertainment of cardiovascular malformations in infants with Down's syndrome, Atlanta, 1968 through 1989. Implications for the interpretation of increasing rates of cardiovascular malformations in surveillance systems. AB - Several birth defects surveillance systems have shown an upward trend in the birth prevalence of several congenital cardiovascular malformations. Improvements in clinical ascertainment have been suggested as an explanation for this increase. For several decades, 40-50% of infants with Down's syndrome have been reported to have cardiac defects associated with the unbalanced genotype. Therefore, secular changes in the frequency of ascertained cardiovascular malformations among infants with Down's syndrome in surveillance systems could shed light on improvements in the ascertainment of these defects. The authors examined changes in the frequency of ascertained cardiovascular malformations among 532 cases of Down's syndrome recorded in the Metropolitan Atlanta Congenital Defects Program from 1968 through 1989. Overall, 33% of the cases have reported cardiovascular malformations. However, the frequency of these defects in Down's syndrome infants increased dramatically from about 20% in the early 1970s to more than 50% in the late 1980s (p = 0.0001). This upward trend was seen for all major categories of cardiac defects and persisted after the cases were stratified by race, sex, maternal age, hospital of birth, birth weight, and gestational age. These results show improvement in the ascertainment of cardiovascular malformations among Down's syndrome infants in a surveillance population. They are also consistent with the hypothesis that the increasing rates of cardiac defects are related, at least in part, to improved ascertainment of these defects in the population. PMID- 1288276 TI - Association of serum albumin with blood pressure in the normative aging study. AB - Little is known regarding serum albumin's epidemiologic relation to chronic disease. The relation of serum albumin to blood pressure was assessed in a longitudinal study of men who have been seen at 3- to 5-year intervals since the early 1960s. The authors analyzed data from over 20 years of observation using cross-sectional multiple regression models of blood pressure that allow for the correlation between repeated measures on the same individual (GLMIC models), longitudinal GLMIC models that incorporate terms for the interaction of time with serum albumin at baseline, and models of the slope of individuals' blood pressure over time. Serum albumin levels were found to have a consistently strong relation with both systolic blood pressure and diastolic blood pressure in the cross sectional GLMIC models only. This relation did not change appreciably when covariates for age, body mass index, alcohol ingestion, smoking, serum calcium, hematocrit, heart rate, and antihypertensive medications were added. A rise in serum albumin of 1 g/dl was associated with 1.79-mmHg and 0.91-mmHg increases in systolic blood pressure and diastolic blood pressure, respectively. This phenomenon may be related to experimental studies linking tryptophan, the only amino acid to bind noncovalently to serum albumin, to a blood pressure-lowering effect mediated by promotion of 5-hydroxytryptamine synthesis in the brain. PMID- 1288277 TI - Obesity and body fat distribution in relation to the incidence of non-insulin dependent diabetes mellitus. A prospective cohort study of men in the normative aging study. AB - The relation between the abdominal accumulation of body fat, total-body adiposity, and blood glucose level and the risk of non-insulin-dependent diabetes mellitus was evaluated prospectively among 1,972 male participants in the Department of Veterans Affairs Normative Aging Study cohort. The risk of non insulin-dependent diabetes mellitus was assessed by means of the proportional hazards model; 226 cases of diabetes occurred among the 1,972 men (mean age at entry, 41.9 years; range, 22-80 years) over 35,496 person-years of observation. The relation of body mass index to diabetes risk was partly explained by body fat distribution; after adjusting for age, the ratio of abdominal circumference to hip breadth, and cigarette smoking, men in the top tertile for body mass index had a 1.3-fold greater risk of diabetes than did men in the lowest tertile (95% confidence interval 0.9-1.8). Moreover, after adjusting for age, body mass index, and cigarette smoking, men in the top tertile for the ratio of abdominal circumference to hip breadth had a 2.4-fold greater risk of diabetes than did men in the lowest tertile (95% confidence interval 1.7-3.7). When blood glucose was analyzed as a continuous outcome variable, the findings were consistent, i.e., a positive association with abdominal fat independent of total-body adiposity. These results confirm previous reports of a prospective relation between abdominal adiposity and the risk of diabetes and provide prospective evidence of a relation between blood glucose levels and both body fat distribution and obesity. PMID- 1288278 TI - Tracking of serum fatty acid composition: a 6-year follow-up study in Finnish youths. AB - The composition of fatty acids in serum cholesteryl esters was analyzed with gas chromatography in 759 Finnish boys and girls aged 3-18 years in 1980 and again in the same subjects in 1983 and in 1986. The mean percentage of linoleate (18:2 n 6) increased from 50.85% in 1980 to 52.60% in 1986, while there was a decrease in myristate (14:0), palmitate (16:0), and eicosapentaenoate (20:5 n-3). The percentage of oleate (18:1) did not change. The stability (tracking) of cholesteryl ester fatty acid composition was examined by calculating linear correlation coefficients among the percentages of each fatty acid at the three study points. For linoleate, 3- and 6-year tracking correlations were 0.59-0.61 and 0.50, respectively; they were of about the same magnitude for arachidonate (20:4 n-6) and lower for the other fatty acids. Results indicate that the serum cholesteryl ester fatty acid composition has somewhat lower tracking than the total cholesterol concentration. The changes in the mean fatty acid composition of the study population obviously reflect a shift from saturated to unsaturated dietary fats. PMID- 1288279 TI - Is there etiologic heterogeneity between upper and lower neural tube defects? AB - Neural tube defects are thought to arise from two different embryologic mechanisms depending on the level of the defect: neurulation defects associated with anencephaly and upper spina bifida and canalization defects associated with lower spina bifida. To investigate whether the risk profiles of neural tube defect cases differ according to the level of the defect, the authors examined data from the Atlanta Birth Defects Case-Control Study. Cases were infants live- or stillborn from 1968 to 1980 with these defects, and controls were infants without defects randomly selected and frequency matched to cases by race, birth year, and hospital of birth. By multivariate polychotomous logistic regression, 1,186 controls were compared with cases: 145 with anencephaly, 59 with upper spina bifida (cervical/thoracic lesions), and 100 with lower spina bifida (lumbar/sacral lesions). Infant's sex and sibling recurrence of neural tube defects were the only factors for which the case subgroups significantly differed in risk. The risks associated with selected maternal exposures during the first trimester of pregnancy did not differ among the case subgroups. Although these results do not support the concept that upper and lower neural tube defects differ in risks from exogenous factors, differences in sibling recurrence and in risks by sex between the two groups suggest an underlying heterogeneity in genetic susceptibility factors. PMID- 1288280 TI - Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. AB - To define better the epidemiology and clinical impact of hepatitis delta virus (HDV) infection among hepatitis B virus (HBV) carriers in less developed countries, the authors prospectively studied a cohort of 216 Yucpa Indian HBV carriers in Venezuela. HBV carriers were followed regularly between 1983 and 1988 by physical examination, laboratory testing for liver enzymes and HBV and HDV markers, and epidemiologic history. Among the cohort, 74 (34%) were initially positive for HDV infection, and 35 additional persons became infected during the study. Risk factors for new HDV infection included living in southern Yucpa villages; being young adults (15-19 years) or young children (1-9 years), and living in a household with a person with acute HDV infection. Persons with HDV infection were at high risk of developing chronic liver disease; 56% of HDV infected persons had moderate-to-severe chronic liver disease at the end of the study compared with none of the HBV carriers without HDV infection. Mortality rates were 6.9% and 8.8% per year, respectively, among initially HDV-positive HBV carriers and those with new HDV infection, because of rapidly progressive chronic liver disease and fulminant hepatitis; mortality was significantly lower in HBV carriers without HDV infection and in non-HBV carriers. HDV superinfection is a devastating disease in HBV carriers in tropical South America. Prevention of HBV infection with hepatitis B vaccine is the best available tool to reduce the impact of this problem. PMID- 1288281 TI - Social intervention and the elderly: a randomized controlled trial. AB - A randomized controlled trial was set up in 1985 to test the effect of social intervention over 3 years among elderly people, aged 75 and above, living alone. The sampling frame was the age/sex register of a large group practice of 12 general practitioners serving the town of Melton Mowbray, Leicestershire, England, with a list size of approximately 32,000 patients. A total of 523 elderly people living alone in 1985 were identified, interviewed, and randomized into experimental and control groups. A lay worker offered the experimental group (n = 261) individual packages of support that aimed at enhanced social contacts. The outcome measures, approximately 3 years later in 1988, were mortality; changes in physical status; demand for medical, paramedical, social, and voluntary services; and changes in a number of subjective variables (morale, loneliness, and self-perceived health). No significant differences were found for any of the variables with the exception of self-perceived health status, where the experimental group showed significantly greater improvements than did the control group. More importantly, half the elderly in this sample declined several offers of help. PMID- 1288283 TI - Re: "A method for estimating HIV transmission rates among female sex partners of male intravenous drug users". PMID- 1288282 TI - Air pollution and school absenteeism among children in Mexico City. AB - To determine the acute effects of ozone exposure, the authors conducted a short follow-up study of respiratory illness in a population of 111 preschool children frequently exposed to ozone levels that regularly exceed 0.120 parts per million (ppm). The children attended a private kindergarten in the southwestern part of Mexico City. Parents completed a questionnaire on demographic data, medical history, and potential sources of indoor air pollution. To determine the relation of ozone and respiratory-related school absenteeism, the authors used a logistic regression model for longitudinal data. During the 3-month follow-up, 50% of the children had at least one respiratory-related absenteeism period, and 11.7% had two or more. Children exposed for 2 consecutive days to high ozone levels (> or = 0.13 ppm) had a 20% increment in the risk of respiratory illness. For children exposed for 2 consecutive days to a high ozone level and the previous day to low temperature (< or = 5.1 degrees C), the risk reached 40% (odds ratio = 1.44, 95% confidence interval 1.37-1.52). This study suggests that ozone exposure might be positively associated with the risk of respiratory illness in children and that it may have an interactive effect with low temperature exposure. PMID- 1288284 TI - Relationship of plasma alpha tocopherol to index of clinical severity in individuals with sickle cell anemia. AB - Several parameters of micronutrition related to antioxidant activity are reduced in individuals with sickle cell anemia (SCA). The data presented here suggest that vitamin E, specifically alpha tocopherol, has a significant correlation (r = -0.38, P < 0.04) with a retrospective survey of clinical events and a significant correlation with a prospective survey of clinical events (r = -0.42, P < 0.03). The survey of clinical events score takes into account important vaso-occlusive manifestations in SCA. Differences in plasma vitamin E levels explained about 15% of the variability in the clinical manifestations of SCA in the population studied. Previously reported data from our lab suggests that the differences in alpha tocopherol levels are not related to dietary intake. Vitamin E may play an important role in modulating the ability of sickle hemoglobin containing erythrocytes to produce vaso-occlusion. Alternatively, it may simply be a marker of disease activity. Studies are ongoing at our center to determine if the relationship of alpha tocopherol to clinical events is causal. PMID- 1288285 TI - Cytogenic characterization of primary refractory anemia. AB - Refractory anemia (RA) is the only myelodysplastic syndrome (MDS) devoid of quantitative marrow diagnostic criteria. The diagnosis rests mainly on the subjective identification of qualitative abnormalities according to the French American-British criteria (FAB) involving one or more bone marrow hematopoietic cell lineages. The occurrence of nonrandom chromosome abnormalities remains the hallmark of the disease and the only means of investigation which confirms the disease objectively. With the purpose in mind to further characterize RA among MDS, we have undertaken a prospective high resolution banding chromosome analyses of bone marrow cells in patients with primary refractory anemia (PRA) with the aim of defining a cytogenetic phenotype and of assessing the clinical relevance of clonal abnormalities at initial diagnosis. Of 39 patients consecutively referred for chromosome analyses with a diagnosis of RA according to the FAB criteria, 27 patients had PRA and fulfilled our criteria for adequate chromosome analyses. Median age was 68 years. Fourteen of 27 patients (52%) had clonal chromosomal abnormalities at diagnosis. None of the patients showed a complex karyotype; 9/14 (64%) had a mixture of normal and abnormal cells. Interstitial or terminal deletions, involving chromosomes 5, 6, 7, 9, 11, 12, and 20, were found in 11/14 (79%) of the patients. Comparison of survival between patients with and without abnormalities showed no difference. The presence of clonal abnormalities did not predict transformation to acute myeloblastic leukemia (AML) nor was it associated with poor survival. In this study, patients with PRA were found to have a predominant pseudodiploid karyotypic pattern characterized by interstitial and/or terminal deletions as opposed to derivatives, specific and non-specific balanced translocations, or other structural and numerical abnormalities. We were unable to reveal any prognostic significance to the presence of these clonal abnormalities at initial diagnosis. PMID- 1288287 TI - Reduced erythropoietin secretion in senile anemia. AB - To investigate the etiology of the age-related decrease in hemoglobin (Hb) concentration, we measured serum erythropoietin (EPO), serum iron, total iron binding capacity, and serum ferritin levels in 247 elderly subjects aged 60-99 years. EPO levels were determined by radioimmunoassay. An age-related increase in the serum EPO concentration (r = 0.220; P < 0.01) and a significant inverse relationship between EPO and Hb concentrations were found in normal elderly subjects without anemia (r = -0.302; P < 0.001), but not in 111 younger controls. Serum EPO levels were slightly higher in elderly subjects with pre-anemic iron deficiency than in the normal elderly subjects (P < 0.05). These results suggest that the EPO secretion is accelerated in the elderly even though the Hb remains above 12.0 g/dl, probably as a compensatory mechanism for peripheral tissue hypoxia. An inverse relationship between the EPO and Hb concentrations was found in the elderly subjects with iron deficiency anemia, but not in those with unexplained senile anemia. The changes of EPO levels were also assessed in 20 elderly subjects who had developed anemia when reviewed after 12 months. Serum EPO levels increased in relation to the decrease in Hb concentration in those with iron deficiency anemia, but not in those with unexplained senile anemia. Reduced EPO secretion thus seems to play a role in the progression of unexplained senile anemia, and recombinant human EPO may possibly be effective for treating this type of anemia by mobilizing excess iron. PMID- 1288286 TI - Essential thrombocythemia in pregnancy: platelet count and pregnancy outcome. AB - We report our experience of 4 successful pregnancies (including a pair of twins) in 3 women who have essential thrombocythemia (ET). All of the patients had a significant fall in platelet count (> 20% of non-pregnant state) during the course of the pregnancy. A review of the literature and our own experience suggests that the degree of platelet count reduction may be correlated with pregnancy outcome. Close monitoring of the platelet count is useful in the management of these cases. PMID- 1288288 TI - Interleukin-2 production by primary adult T cell leukemia tumor cells is macrophage dependent. AB - We have investigated the cellular requirements for IL-2 production by autocrine proliferating tumor cells from four patients with adult T cell leukemia (ATL). Cultures of these ATL cells both produced endogenous IL-2 protein in the absence of added mitogen and proliferated at higher levels when exogenous recombinant IL 2 was added. Depletion of macrophages in the tumor cell cultures resulted in a sharp decline in tumor cell IL-2 production, while re-addition of macrophages reconstituted this response. Macrophage-derived factors including IL-6 and IL-1 also reconstituted IL-2 production in these macrophage depleted cultures. These results raise the possibility that macrophages may play a central role in HTLV-I mediated immortalization of T cells. PMID- 1288289 TI - Angiodysplasia and von Willebrand's disease type IIB treated with estrogen/progesterone therapy. AB - The association between angiodysplasia and von Willebrand's disease was first reported in 1967. The cases reported to date have involved patients with type I and IIA von Willebrand's disease. We report a patient with type IIB von Willebrand's disease who suffered gastrointestinal bleeding attributable to gastric angiodysplasia. The patient underwent endoscopic electrocautery acutely and has been treated long-term with estrogen/progesterone therapy. She has suffered no recurrent gastrointestinal bleeding at over 11 months of follow-up. We suggest hormonal therapy as an alternative to repeated blood product transfusion or extensive surgical resection in patients with von Willebrand's disease and gastrointestinal bleeding from angiodysplasia. PMID- 1288290 TI - Proliferation of abnormal bone marrow histiocytes, an undesired effect of granulocyte macrophage-colony-stimulating factor therapy in a patient with Hurler's syndrome undergoing bone marrow transplantation. AB - Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2-year-old male with HS who received up to 8 micrograms/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percentage of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases. PMID- 1288291 TI - Intrathoracic extramedullary hematopoietic tumor in hemoglobin H disease. AB - We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with beta thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions. PMID- 1288292 TI - Adult T-cell leukemia developing during immunosuppressive treatment in a renal transplant recipient. AB - We report a case of a 32-year-old male, an asymptomatic carrier of human T-cell leukemia virus type 1 (HTLV-1), who underwent a renal transplantation and developed adult T-cell leukemia (ATL) during the course of posttransplant immunosuppressive treatment. He was treated with combination chemotherapies consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, cisplatin, cytosine arabinoside, etoposide, and methyl-prednisolone, without any improvement. Bestrabucil (KM2210), a conjugate of chlorambucil and estradiol, was administered as an alternative therapy; this therapy successfully suppressed his leukemic cell growth, and partial remission was achieved. Posttransplant immunosuppressive therapy with prednisolone, mizoribine, and cyclosporin A might have been the predominant cause of the transition from an asymptomatic HTLV-1 infection to overt ATL. A careful approach is required with HTLV-1 asymptomatic carriers who need organ transplantation followed by immunosuppressive treatment. PMID- 1288293 TI - Cerebral infarction in a patient with acute lymphoblastic leukemia after fresh frozen plasma replacement during L-asparaginase therapy. PMID- 1288294 TI - No large deletions of mitochondrial DNA in acquired idiopathic sideroblastic anemia (AISA) PMID- 1288295 TI - Transient inhibitor to monoclonal antibody-purified factor VIII concentrate. PMID- 1288296 TI - Plasmacytic ascites responsive to multiagent chemotherapy. PMID- 1288297 TI - Acute and definitive renal failure in progressive multiple myeloma treated with recombinant interferon alpha-2a: report of two patients. PMID- 1288298 TI - Denatured erythrocyte scan to enhance the detection of splenosis. PMID- 1288300 TI - Chronic neutrophilic leukemia: case report documenting the absence of bcr-abl rearrangement. PMID- 1288299 TI - N-ras oncogene activation in a patient with gamma heavy chain disease. PMID- 1288301 TI - T cell-mediated inhibition of erythropoiesis in myelodysplastic syndromes. PMID- 1288302 TI - Case report: all-trans retinoic acid, hyperleukocytosis, and marrow infarction. PMID- 1288303 TI - Agranulocytosis associated with pyrithioxine therapy. PMID- 1288304 TI - Expert psychiatric evidence in sexual misconduct cases before state medical boards. AB - The growing problem of physician sexual misconduct has captured the attention not only of the medical and legal communities, but of the public as well. State medical boards, administrative agencies with generous rules of evidence and varying levels of expertise, face the difficult task of responding to patients' allegations of physician sexual abuse. This Article, based in large part on the author's survey of current state medical board practice, reveals an increasing reliance on expert psychiatric testimony to explain the behavior of complainants and accused physicians. Drawing analogies from the use of psychiatric evidence in child sexual abuse cases, the author examines the factors that boards must consider in determining the admissibility of expert testimony in physician sexual misconduct cases, and calls upon states to establish clear evidentiary rules to govern the use of such testimony in administrative hearings. PMID- 1288305 TI - Access to medical care for HIV-infected individuals under the Americans with Disabilities Act: a duty to treat. AB - In 1990, Congress enacted the Americans with Disabilities Act (ADA). This Note examines the legislative history of the ADA and uncovers Congress's intent to impose a duty on health care providers to treat people with disabilities unless an individual poses a "direct threat" to the health or safety of others. This Note posits that, with the passage of the ADA, Congress imposed a statutory duty on health care providers to give care to people infected with HIV who qualify under the statute. This Note concludes that while the "direct threat" exception may lessen the impact of the ADA, those infected with HIV should enjoy greater access to health care than ever before. PMID- 1288306 TI - Short-sheeting the psychiatric bed: state-level strategies to curtail the unnecessary hospitalization of adolescents in for-profit mental health facilities. AB - Over the past decade, there has been an increase in the hospitalization of minors in private, for-profit, psychiatric facilities. This increase suggests a tension between what is medically necessary and what is financially desirable. This Note discusses the hospitalization of minors in private, for-profit, mental health facilities and its attendant implications. This Note then examines various state efforts aimed at protecting minors from inappropriate psychiatric hospitalization. Finally, while there is no catch-all solution to the problem, this Note offers specific recommendations for reforming the for-profit psychiatric industry. PMID- 1288307 TI - AIDS: constitutionality of mandatory HIV testing of convicted prostitutes- Illinois v. Adams. PMID- 1288308 TI - AIDS: court-ordered HIV testing of crime victims--Florida v. Storm. PMID- 1288309 TI - Blood industry: discovery from anonymous donors--Watson v. Lowcountry Red Cross. PMID- 1288310 TI - Blood industry: standard of care--United Blood Service v. Quintana. PMID- 1288311 TI - Increasing survival of extremely low birthweight infants in Alaska. AB - The survival and characteristics of extremely premature infants with a birthweight between 500 and 750 grams, who were treated at Providence Hospital newborn intensive care unit, were reviewed over the years 1987 to 1989. Forty infants were admitted and treated. Survival increased from 21 percent in 1987, 47 percent in 1988 to 82 percent in 1989. Changes in perinatal and neonatal factors over the three years were reviewed and comparisons between survivors and non survivors were analyzed. Stepwise regression analysis revealed significant increases in the incidence of chorioamnionitis and birthweight over the period. Increased survival was noted even when infants from 1989, who received artificial surfactant, were excluded (survival increased from 21 percent in 1987 to 75 percent in 1989). Recent literature on extremely low birthweight infants, including neurodevelopmental outcome, is reviewed. Survival of extremely low birthweight infants in Alaska is increasing because of multiple changes in obstetrical and pediatric practices. PMID- 1288312 TI - Apnea of prematurity: theophylline v. caffeine. AB - During a fifteen month period, 401 two channel (heart rate and respiratory impedance), 12 hour pneumocardiograms on 277 preterm infants were performed. Each pneumocardiogram was evaluated according to the following set of criteria: prolonged apnea (apnea > 19 seconds or shorter if associated with heart rate of < 80bpm for > 2 seconds or observed cyanosis); short apnea (apnea 10-19 seconds); periodic breathing (normal respiratory pattern interrupted by > 2 breathing pauses of > 5 seconds during > 1 minute duration). Apnea density was used as prime measure in determining abnormal pneumocardiograms and was defined by total apnea time (seconds) x 100 divided by recording time while periodic breathing index defined by total periodic breathing time (minutes) x 100 divided by recording time. Sixty infants (24%) had apnea densities > or = 5 which prompted therapy with theophylline. Sixteen of these infants (27%) failed to resolve their apnea within 7 days (apnea density > or = 3) and were placed on caffeine citrate. Caffeine decreased the apnea density of fourteen of these infants (88%) to 0.8 (95% CI; 0-2.3). Efficacy of both methylxanthines to normalize the pneumocardiogram was similar (p = 0.5). Persistent apnea unresponsive to theophylline may respond to orally administered caffeine citrate. PMID- 1288313 TI - An update on WAMI in Alaska. PMID- 1288314 TI - When a doctor plays judge. PMID- 1288316 TI - "What is the matter, doctor?" Infertility: Part 2. PMID- 1288315 TI - An opportunity for health-system reform. PMID- 1288317 TI - History of medicine in Alaska. A. Holmes Johnson, M.D. PMID- 1288318 TI - A baffling disease from the land of volcanoes (1835-1840). PMID- 1288319 TI - Time-resolved X-ray diffraction studies on the mechanism of active Ca2+ transport by the sarcoplasmic reticulum Ca2+ ATPase. PMID- 1288320 TI - A proteolipid associated with the plasma membrane H(+)-ATPase of fungi. PMID- 1288321 TI - Structure and function of the yeast plasma-membrane H(+)-ATPase. PMID- 1288322 TI - The KDP ATPase of Escherichia coli. PMID- 1288323 TI - Mg2+ transporting P-type ATPases of Salmonella typhimurium. Wrong way, wrong place enzymes. PMID- 1288324 TI - Structure and properties of the coated vesicle proton pump. PMID- 1288325 TI - Structure, function, and mutational analysis of V-ATPases. PMID- 1288326 TI - The plasma membrane ATPase of archaebacteria. A chimeric energy converter. PMID- 1288327 TI - Sodium-translocating adenosinetriphosphatase of Propionigenium modestum. PMID- 1288328 TI - Long-range intramolecular linked functions in activation and inhibition of SERCA ATPases. PMID- 1288329 TI - Correlations of structure and function in H+ translocating subunit c of F1F0 ATP synthase. PMID- 1288330 TI - Escherichia coli F0F1-ATPase. Residues involved in catalysis and coupling. AB - The molecular biological approach has provided important information toward understanding the complexities of the F0F1 ATPase. This article focuses on our recent results on the ATPase catalytic site contained in the beta subunit and the role of the gamma subunit in regulation of proton transport. We used a combination of affinity labeling and mutagenesis to locate several residues of the alpha and beta subunits in the catalytic site. Adenosine triphosphopyridoxal (AP3-PL) labeled beta Lys-155, beta Lys-201 and alpha Lys-201, suggesting that they are near the gamma-phosphate moiety of ATP. Turning to a mutagenesis approach we demonstrated that the two conserved residues, beta Lys-155 and beta Thr-156 in the glycine-rich sequence, are essential for catalysis. Finally, using pseudorevertant analysis, we positioned residue beta Gly-149 (also in the glycine rich sequence) in proximity to beta Ser-174, beta Glu-192 (binding site for DCCD), and beta Val-198 (only three residues away from the AP3-PL binding site, beta Lys-201). Genetic studies suggested that the gamma subunit plays a role in regulation of catalysis and its coupling with proton conduction. We found that four mutations in the carboxyl-terminal region (gamma Gln-269-->Leu, gamma Gly 275-->Lys, gamma Thr-277-->end, or frameshift) had similar membrane ATPase activities but different ATP-dependent proton pumping and growth by oxidative phosphorylation. These results suggested a perturbation in the coupling between catalysis and proton translocation. We were able to clearly define the "uncoupling" by introducing mutations in the amino-terminal region of the gamma subunit. We were led to gamma Met-23-->Lys and Arg which resulted in an enzyme still regulated by delta microH+, but with profoundly inefficient coupling between ATPase catalytic sites and proton translocation in both ATP-dependent proton pumping and delta microH(+)-driven ATP synthesis. Second-site mutations in the carboxyl-terminal region of the gamma subunit reversed this effect. PMID- 1288331 TI - F0 and F1 subunits involved in the gate and coupling function of mitochondrial H+ ATP synthase. PMID- 1288332 TI - F-type ATPases: are nucleotide domains in adenylate kinase appropriate models for nucleotide domains in ATP synthase/ATPase complexes? PMID- 1288333 TI - The alpha 3 beta 3 and alpha 1 beta 1 complexes of ATP synthase. AB - Two catalytic structures of H(+)-motive ATP synthase (Fig. 1), the alpha 3 beta 3 oligomer (M(r) = 319,581) and alpha 1 beta 1 promoter (M(r) = 106,527) (Fig. 2), were isolated using high pressure liquid chromatography (Fig. 3) and polyacrylamide gel electrophoresis (Figs. 4 and 5). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 oligomer was also crystallized. Common to both F1 and the alpha 3 beta 3 oligomer were the nucleotide specificity, the two Km values, the presence of protomer oligomer activities, and the one-hit--one-kill phenomenon. A synchrotron experiment on the ATP hydrolysis cycle revealed the dynamic shrinkage and expansion of F1(44) that correspond, respectively, to the ATP-induced association and ADP-induced dissociation of the alpha 3 beta 3 oligomer. The oligomer, like mitochondrial F1 and TF1, exhibited two kinds of ATPase activity: one was cooperative and was inhibited by only one inhibitor per hexamer, and the other was inhibited by three inhibitors per hexamer. PMID- 1288334 TI - Unisite and multisite ATP hydrolysis and synthesis by bovine submitochondrial particles. PMID- 1288335 TI - Study of the lipid-protein interaction of F ATPases. AB - Mg2+ may play a role in altering the lipid fluidity of the bilayers which would induce a change in conformation of the F0 portion of the H(+)-ATPase complex. This change could be transmitted to the soluble F1 portion, the conformation of which is in turn altered, resulting in higher enzymic activity. In addition to mitochondrial H(+)-ATPase, similar Mg2+ effects on the reconstitution of chloroplast H(+)-ATPase and other intrinsic membrane proteins have also been observed in our laboratory. PMID- 1288337 TI - Structure/function analysis of yeast mitochondrial ATP synthase subunit 8. AB - Subunit 8 of yeast mitochondrial ATP synthase is a small hydrophobic component of the membrane-associated F0 sector. Structure/function relations in subunit 8 were studied by focusing on three structural domains: a highly conserved NH2-terminal region, a central hydrophobic region (previously suggested to be a transmembrane stem), and a COOH-terminal region bearing a conserved array of three positively charged residues. A combined approach was used, which encompasses site-directed mutagenesis, in vitro import and assembly tests, and an in vivo allotopic expression system (using host cells unable to synthesise subunit 8 in mitochondria). The results indicate that the NH2-terminal region of subunit 8 is involved functionally in the F0 sector. As the central hydrophobic region can functionally tolerate the introduction of multiple, positively charged residues (which abolishes the proteolipid solubility characteristics of the entire subunit), the role of this hydrophobic region as a transmembrane stem is brought into question. Each of the three positively charged residues toward the COOH terminus of subunit 8 is required for the efficient assembly of this subunit into the F0 sector. Removal of the more proximal charged residues Arg37 or Arg42 has a more severe impact on subunit 8 assembly than does removal of the most distal residue Lys47 in terms of both in vitro import and assembly as well as the ability of the subunit 8 variant to function in mitochondrial ATP synthase in vivo. PMID- 1288336 TI - Age-related changes of mitochondrial F0F1 ATP synthase. PMID- 1288338 TI - Ca(2+)- and Mg(2+)-ATPases in the Golgi apparatus and microsomes of the lactating mammary glands of cows. PMID- 1288339 TI - Binding of gadolinium ions to sarcoplasmic reticulum membranes. PMID- 1288340 TI - Different solute sensitivity of the RBC plasma membrane Ca(2+)-ATPase activation in the calmodulin-dependent and calmodulin-independent pathways. PMID- 1288341 TI - Transport, hydrolysis, and phosphoenzyme formation of a prokaryotic Ca(2+) ATPase. PMID- 1288342 TI - Localization of mRNA coding for plasma membrane Ca-ATPase isoforms in rat brain by in situ hybridization. PMID- 1288344 TI - Photoaffinity labeling and expression cloning of extracellular ATP receptors of cardiac myocytes. PMID- 1288343 TI - Identification and characterization of a candidate phosphatidylserine transporting ATPase. PMID- 1288345 TI - A plasma membrane V-type H(+)-ATPase may contribute to elevated intracellular pH (pHin) in some human tumor cells. PMID- 1288346 TI - Purification and kinetic characterization of the Kdp-ATPase. PMID- 1288348 TI - Immunoaffinity chromatographic purification of chicken ectoATP diphosphohydrolase. PMID- 1288347 TI - An ATPase operon involved in copper resistance by Enterococcus hirae. PMID- 1288349 TI - On the mechanism of ATP-driven Ca2+ transport by the calcium ATPase of sarcoplasmic reticulum. PMID- 1288350 TI - Potassium-stimulated N,N'-dicyclohexylcarbodiimide-sensitive AtPase activity in the membranes of anaerobically grown Escherichia coli. PMID- 1288351 TI - Antibody identification of a cross-linking product between the mitochondrial ATPase inhibitor and a putative membrane receptor. PMID- 1288352 TI - Upgradings on the energetics of amphibia heart in vitro. Quabain and total tissue transport ATPases. PMID- 1288353 TI - Why the mitochondrial ATPase inhibitor IF1 fails to inhibit the mitochondrial ATPase in situ in fast heart-rate mammalian and avian hearts. PMID- 1288354 TI - Zn2+ allows differentiation between two kinds of IF1-ATPase interaction in intact mitochondria. PMID- 1288355 TI - cDNA cloning of possible mammalian homologs of the yeast secretory pathway Ca(2+) transporting ATPase. PMID- 1288356 TI - Cellular proteolysis. An overview. PMID- 1288357 TI - An endosomal-lysosomal pathway for degradation of amyloid precursor protein. AB - We previously reported evidence for a lysosomal degradative pathway for APP and C terminal fragments thereof, based on Western and immunocytochemical analysis of drug-treated cells. Here, we verify the existence of a lysosomal degradative pathway for APP using pulse chase immunoprecipitation analysis of drug-treated cells and fibroblasts with and without a known lysosomal hydrolase targeting defect. The results are consistent with the hypothesis that part or all of the beta-protein domain of APP is normally degraded by lysosomes. A mechanism for beta-protein deposition based on this data is hypothesized. PMID- 1288359 TI - Normal processing of the Alzheimer's disease amyloid beta protein precursor generates potentially amyloidogenic carboxyl-terminal derivatives. PMID- 1288358 TI - Amyloid beta/A4 precursor protein (APP) processing in lysosomes. AB - Alzheimer's disease (AD) is characterized by the formation of senile plaques, the main component of which is amyloid beta protein. The processing of the amyloid beta/A4 protein has been implicated in the pathogenesis of AD. We have reported cathepsin B as a candidate APP secretase. By using APP-transfected COS-1 cells, we determined that the putative APP secretase, lysosomal cathepsin B, is involved in the constitutive processing of the precursor molecule. Digestion experiments demonstrated that cathepsin B cleaves the APP molecule into two fragments with molecular masses 115 kDa and 9 kDa, representing presumptive proteolytic fragments of constitutive processing. PMID- 1288360 TI - Protein metabolism in the brain. PMID- 1288361 TI - The involvement of proteases, protease inhibitors, and an acute phase response in Alzheimer's disease. PMID- 1288362 TI - Purification and cloning of brain proteases capable of degrading the beta-amyloid precursor protein. PMID- 1288363 TI - Degradation of proteins in the membrane-cytoskeleton complex in Alzheimer's disease. Might amyloidogenic APP processing be just the tip of the iceberg? PMID- 1288364 TI - Proteolytic mechanism for the neurodegeneration of Alzheimer's disease. PMID- 1288366 TI - Relevance of the balance between glia-derived nexin and thrombin following lesion in the nervous system. PMID- 1288365 TI - Regulation of neuronal cells and astrocytes by protease nexin-1 and thrombin. PMID- 1288367 TI - Potential role of protease nexin-2/amyloid beta-protein precursor as a cerebral anticoagulant. AB - The amyloid beta-protein precursor (APP) is the parent molecule to the amyloid beta-protein which is a major constituent of neuritic plaques and cerebrovascular deposits in Alzheimer's disease (AD). The protease inhibitor, protease nexin-2 (PN-2), is the secreted form of APP that contains the Kunitz protease inhibitor (KPI) domain. We reported that the predominant isoform of APP in human brain contains the KPI domain and is thus PN-2. Quantitation of PN-2/APP in various tissues revealed that it is primarily found in brain. Circulating blood platelets are another rich source of PN-2/APP. Platelet PN-2/APP is contained in platelet alpha granules and is secreted upon activation of platelets by physiological agonists. Protease inhibition measurements demonstrated that PN-2/APP is a potent inhibitor of intrinsic blood coagulation factor XIa. These findings suggest that PN-2/APP may play a role in the regulation of blood coagulation and platelets may serve as a systemic vehicle to deliver large amounts of this protein to sites of vascular injury. In addition, we propose that the rich, and relatively exclusive, investment of PN-2/APP in brain suggests that it may function locally as an intracerebral anticoagulant. PMID- 1288368 TI - Translocation of proteins across and integration of membrane proteins into the rough endoplasmic reticulum. PMID- 1288369 TI - Sorting of chromogranin B into immature secretory granules in pheochromocytoma (PC12) cells. AB - Two tyrosine sulfated proteins, chromogranin B and secretogranin II, are targeted into regulated secretory granules, which are stored until stimulation causes them to fuse with the plasma membrane. In PC12 cells, [35S]-sulfate labels chromogranin B, secretogranin II and proteoglycans just before they are sorted into the regulated and constitutive secretory pathways. Chromogranin B was secreted by both the regulated and constitutive secretory pathways. In contrast, very little secretogranin II was secreted constitutively. Formation of regulated and constitutive secretory vesicles from the trans Golgi network was reconstituted in vitro. Mechanically permeabilized PC12 cells released regulated and constitutive vesicles containing sulfated markers. At early chase times, chromogranin B was predominantly released from permeabilized cells in small vesicles that comigrated with constitutive secretory vesicles containing proteoglycans. At intermediate chase times the vesicles containing chromogranin B resembled immature secretory granules containing secretogranin II. At very long chase times chromogranin B and secretogranin II were found in mature secretory granules that did not escape the permeabilized cells in vitro. We conclude that chromogranin B is sorted into immature regulated secretory granules with lower efficiency than secretogranin II. PMID- 1288370 TI - Secretion of the beta-amyloid precursor protein. PMID- 1288371 TI - Selective degradation of cytosolic proteins by lysosomes. AB - Lysosomes are able to internalize cellular proteins in a variety of ways. One pathway is selective for cytosolic proteins containing peptide sequences biochemically related to Lys-Phe-Glu-Arg-Gln (KFERQ). This pathway is activated in confluent monolayers of cultured cells in response to deprivation of serum growth factors and applies to approximately 30% of cytosolic proteins. We have reconstituted this lysosomal degradation pathway in vitro. Uptake and/or degradation is stimulated by ATP and a member of the heat shock 70-kilodalton protein family, the 73-kilodalton constitutive heat shock protein. Several possible mechanisms of selective protein transport into lysosomes and the possible relevance of this proteolytic pathway to the processing of the amyloid precursor protein are discussed. PMID- 1288373 TI - [Pathogenesis of ruptures of the shoulder rotator cuff]. AB - Rupture of the rotator cuff occurs exceptionally in a healthy cuff and almost always in a degenerated cuff. This degeneration may be either ischaemic and secondarily conflictual or primarily conflictual. There are two zones of conflict: anteromedial and superior, resulting in two clinical presentations: small anterosuperior ruptures which are initially very painful, but minimally disabling and large posterosuperior ruptures which are initially which are immediately disabling but minimally painful. PMID- 1288372 TI - The lysosomal system in neurons. Involvement at multiple stages of Alzheimer's disease pathogenesis. AB - Disturbed lysosomal function may be implicated at several stages of Alzheimer's pathogenesis. Lysosomes and acid hydrolases accumulate in the majority of neocortical pyramidal neurons before typical degenerative changes can be detected, indicating that altered lysosome function is among the earliest markers of metabolic dysfunction in Alzheimer's disease. These early alterations could reflect accelerated membrane and protein turnover, defective lysosome or hydrolase function, abnormal lysosomal trafficking or any combination of these possibilities. Because APP is partly metabolized in lysosomes, early disturbances in lysosomal function could promote the production of abnormal and/or neurotoxic APP fragments within intact cells. Lysosomal abnormalities progressively worsen as neurons begin to degenerate. Based on existing literature on cell death, increased perturbation and instability of the lysosomal system may be expected to contribute to the atrophy and eventual lysis of the neuron. Finally, the release of hydrolase-filled lysosomes and lipofuscin aggregates from dying neurons accounts for the abundant deposition of enzymatically active acid hydrolases of all classes in the extracellular space--a phenomenon that may be unique to Alzheimer's disease. Acting on APP present in surrounding dystrophic neurites, cellular debris and astrocyte processes, dysregulated hydrolases may cleave APP in atypical sequential patterns, thereby generating self-aggregating protease resistant APP fragments that can be only processed to beta-amyloid. Genetic mutations or posttranslational factors of APP should further enhance the generation of amyloidogenic fragments by a dysregulated lysosomal system. Given that very little, if any, beta-amyloid is detected intracellularly, yet extracellular beta-amyloid is very abundant, our data suggest that the final steps of APP processing and the generation of most beta-amyloid in the brain parenchyma occur extracellularly and may involve one or more lysosomal proteases. PMID- 1288374 TI - [Clinical examination of lesions of the rotator cuff]. AB - Although unable to reach any formal conclusions, clinical examination remains an essential prerequisite in the assessment of a rotator cuff lesion, as it guides the diagnosis, evaluates the severity of the functional impairment and often the extent of the lesions and eliminates the differential diagnoses. The principal clinical tests of shoulder conflict are recalled, but as they are painful, they should only be performed at the end of a complete clinical examination. PMID- 1288375 TI - [Radiological exploration of the shoulder rotator cuff]. AB - Plain X-rays and Lecler's manoeuvre constitute the essential basic assessment in the diagnostic approach to lesions of the rotator cuff. The preoperative assessment of the lesions and the search for associated lesions are based on more or less invasive investigations. For many years, arthrography was the reference examination to establish a precise assessment, but was sometimes insufficient for the diagnosis of small partial non-communicating lesions and certain longstanding massive ruptures. Ultrasonography is an attractive non-invasive technique, but the quality of the results depends on the operator's experience. Although computed tomography and CT arthrography provide a perfect analysis of the anterior aspect of the cuff and evaluate the trophicity of the muscles, they are difficult to interpret, irradiating and sometimes incomplete. MRI, a non-invasive and non-irradiating technique, is the modality of choice due to its excellent contrast resolution and the possibility of multidirectional studies and a spatial resolution which is continually improved by new acquisition sequences and the use of better adapted surface coils. PMID- 1288376 TI - [Ultrasonography of the shoulder: diagnosis of rupture of tendons of the rotator muscles]. AB - After a short historical review of the use of ultrasonography to study shoulder rotator tendons, the technique of the investigation is described, as well as the main landmarks, findings indicative of complete rotator cuff tear, and limitations of ultrasonography in this indication. A number of issues concerning the preoperative workup are discussed. Results in a prospective study of 24 patients are reported. Findings upon ultrasonography, arthrography, and surgical exploration in these patients are analyzed comparatively. Sensitivity and specificity of ultrasonography for the diagnosis of complete rotator cuff tear (RCT) were 95% and 100%, respectively. These data show that ultrasonography is a reliable investigation for confirming, detecting, and evaluating RCT, although extensive experience with the technique is required. PMID- 1288377 TI - [Contribution of gradient-echo MRI in the study of subacromial pathology: correlation between surgery and arthrography]. AB - 30 asymptomatic volunteer subjects and more than 400 patients with suspected rotator cuff lesions were examined by MRI at 0.5 T using T2*-PD weighted gradient echo (T2-GEI) sequences. Its superiority over T2 spin echo imaging was established in previous studies. The results were compared to those of surgery in 87 cases and arthrography in 233 cases (associated with CT arthrography in 70 cases). In the operated patients, T2-GEI and arthrography correctly diagnosed 49 complete ruptures (CR). T2-GEI was found to be superior to arthrography for defining the real extent of the rupture, the degree of tendon retraction and the local muscular trophicity, essential information to define the therapeutic indications. In contrast, among 22 lesions of the long biceps tendon, correctly demonstrated by arthrography or CT arthrography, 5 intracapsular lesions were not detected by MRI. MRI was able to detect 8 lesions of the anterior labrum associated with a CR not demonstrated by arthrography. Lastly, among the 18 cases of partial inferior rupture (PIR), 6 partial superficial ruptures and 14 cases of inflammatory changes, correctly diagnosed by MRI, only 8 PIR were also demonstrated by arthrography. For the non-operated patients investigated by the two modalities (146 cases), T2-GEI and arthrography were concordant in 43 cases. In contrast, 103 intact cuffs on arthrography showed features on T2-GEI compatible with tendinopathy without rupture, bursitis and degenerative changes. In the absence of very fine surgical or histological correlations for these small lesions, it is impossible, at the present time, to determine the real sensitivity and specificity of MRI. PMID- 1288378 TI - [Sub-acromio-deltoid bursography]. AB - Subacromio-deltoid bursography may be diagnostic and/or therapeutic. As a diagnostic procedure, it opacifies the bursa, which may be more or less fused. It visualises the superior surface of the cuff, which may be fissured and it demonstrates exaggerated impression of the acromio-coracoid ligament. It is only indicated when arthrography of the shoulder is normal. As a therapeutic procedure, it constitutes a more sensitive test than Neer's test. When it is negative, the diagnosis of anterior conflict is doubtful. The addition of a corticosteroid prolongs the therapeutic effect and facilitates rehabilitation. PMID- 1288380 TI - [Antero-internal impingement of the shoulder]. AB - Anteromedial conflicts of the shoulder are situated in the subcoracoid or coracohumeral space, in the anterior part of the acromio-coracoid vault. The authors describe a first fibrous band connecting the anterolateral border of the acromio-coracoid ligament to the coraco-biceps tendon (Apoil) and a second deeper band between the superior border of the subscapularis and the insertion of the long head of biceps onto the labrum (Patte). The role of the vault varies according to constitution (length and direction of the coracoid process) and acquired factors (iatrogenic or traumatic); the role of the floor depends on numerous elements: traumatic sequelae (malunion), eccentricity of the humeral pivot, lesion of the rotator interval, variant of insertion of the anterior capsule, floating glenoid labra, anomalies of insertion of pectoralis minor. There are no pathognomonic signs, but Gerber's, Hawkin's and Yocum's signs are generally observed. Computed tomography and CT arthrography are currently the most reliable complementary investigations to demonstrate this type of conflict. This regional pathology is situated at the crossroads between pure conflictual mechanisms and hyperlaxity phenomena associated with subluxations. PMID- 1288379 TI - [X-ray guided puncture-aspiration of refractory calcifications of the shoulder]. AB - Calcifying periarthritis of the shoulder may have either an acute or a chronic course. In both cases, direct puncture of the calcification shortens the natural history and facilitates and accelerates resorption in 50% of cases. The addition of a small amount of corticosteroid relieves the painful syndrome, with 80% good and very good results. The use of low doses of corticosteroid is particularly important in diabetics, patients with peptic ulcer and sportsmen. The puncture technique and the necessary precautions are described. PMID- 1288381 TI - [Clinical examination of shoulder instabilities]. AB - We describe the clinical examination of the different kinds of acute instabilities of the shoulder. In the second part, we report the etiologies and the clinical signs of recurrent instabilities of the shoulder. PMID- 1288382 TI - [Shoulder instabilities. Radiological evaluation]. AB - In case of anteromedial instability of the shoulder, the radiological investigation should start by comparative plain films including glenoid lateral views looking for a lesion of the anteroinferior glenoid margin of the scapula. If plain films are normal, CT arthrography of the shoulder is indicated looking for a lesion of the anteroinferior glenoid labrum. If no traumatic abnormality is present, a plain CT scan may sometimes show glenoid dysplasia, which is frequently bilateral. Posterior dislocation of the shoulder is less common and is obvious on plain films. The inventory of the lesions is established by CT arthrography. In case of multidirectional instability, the radiological investigation determines the preferential direction of instability, generally by means of dynamic manoeuvres. PMID- 1288383 TI - [Multidirectional instabilities and hyperlaxity of the shoulder]. AB - Multidirectional instability is an unusual entity which is frequently missed in the context of unstable shoulder. The diagnosis of this condition may be difficult and is based on demonstration of basic anatomical lesions, usually acquired: capsular distension and damage to the inferior glenohumeral ligament responsible for the inferior component of the instability. Despite a suggestive clinical history, the positive diagnosis is based on a very detailed clinical and radiological examination, performed under general anaesthesia if necessary, in order to define the preferential direction of instability. Conventional and CT arthrography are of undeniable diagnostic and therapeutic value in the context of assessment. First-line treatment should be conservative. When surgery is indicated, it may consist of a combination of bone grafts and capsulorraphy, as described by C.S. Neer. PMID- 1288384 TI - [Destructive arthropathy of the shoulder]. AB - Destructive arthropathy of the shoulder consists of cartilaginous deterioration combined with subchondral osteolysis. The various diseases able to induce joint destruction (infection, neurological disease, chondrocalcinosis, tumour...) are excluded from this description which only concerns the forms with no obvious cause. Since the description of "senile haemorrhagic caries of the shoulder", several authors have reported, under various names, very similar diseases whose common denominator is destruction of the shoulder joint. The pathogenic factors remain unclear, but various theories have been proposed, involving mechanical factors secondary to lesions of the rotator cuff or suggesting the role of apatite microcrystals. PMID- 1288385 TI - [Radiologic anatomy of the shoulder]. AB - That proximal joint, the glenohumeral joint is difficult to examine by simple X rays which explains the numerous lateral views proposed; it is essential to know the precise indications and respective value of each of these views. Arthrography generally combined with computed tomography is an excellent examination for the study of the glenoidal labrum and the capsular structures. In other indications, particularly for the study of the rotator cuff, it tends to be replaced by MRI. PMID- 1288386 TI - [Correlations of CT and MRI imaging of the lateral pterygoid muscle]. AB - On the basis of 15 CT scan and MRI studies of normal volunteers, the authors describe the features the lateral pterygoid muscle. A good correlation appears between CT and MR images which would be useful in the staging of tumors in this space, and in the pathophysiology of internal derangements of the temporomandibular joint (TMJ). PMID- 1288387 TI - [Unusual sites of Pott's disease. Apropos of fourteen cases]. AB - The diagnosis of Pott's disease is generally easy exception unusual sites whose diagnosis is requires cross-section imaging and needle biopsy. The authors report 14 cases of atypical forms of Pott's disease: 7 cases of centro-somatic forms 4 cases of sub-occipital Pott's disease, 2 cases of posterior arch and one case of sub-ligamentous vertebral tuberculosis. The radiological diagnosis of Pott's disease is suggested by the presence of a paravertebral abscess noted in 12 cases tuberculous spondylitis associated in 3 cases and multifocal involvement in 9 cases. PMID- 1288388 TI - [Cystic lymphangioma of the neck in adults. Contribution of ultrasonography and computed tomography. Apropos of a case]. AB - Authors present a case of cystic lymphangioma of the neck in an adult patient. Cystic lymphangioma of the neck can simulate other benign lesions and occasionally extend into the mediastinum. Using computed tomography and ultrasound, the authors are able to confirm the suspected diagnosis, exclude other diagnostic considerations, and demonstrate absence of mediastinal extension. Opportunity of such diagnosis in adult is no frequent. PMID- 1288389 TI - [Cervico-mediastinal cystic lymphangioma]. AB - Anterior cervico-mediastinal tumors in children, especially if they are cystic, often correspond to the diagnosis of cystic hemolymphangioma. CT and Chest US are contributive for the diagnosis and the pre-operative staging. PMID- 1288390 TI - [Post-traumatic gas in children. Apropos of a case]. AB - The authors report a case of post-traumatic gas in the portal vein in a child. They stress the rarity of this lesion in such circumstances and recall the radiological signs together with the differential diagnoses and the principal aetiologies. PMID- 1288391 TI - [Vertebral osteosclerosis, sacro-iliitis and palmoplantar dermatitis. Apropos of a case]. AB - The authors report a case of aseptic vertebral osteitis which they classify in the context of SAPHO in view of the association with unilateral sacro-ileitis and palmoplantar dermatitis. They stress the importance of recognizing this disease which is initially suggestive of either a bone disease (Paget's disease, bone metastasis) or infectious discospondylitis. PMID- 1288393 TI - [Atypical pleural effusion by transdiaphragmatic communication. Apropos of two cases: chylothorax and hydrothorax]. AB - We report two cases of pleural effusion in which a subdiaphragmatic cause was noted. In both cases it was necessary to obliterate a defect in the diaphragm via a thoracic incision. In one case, a left chylothorax occurred in a patient with hepatic cirrhosis. In this case, it was postulated that the normal lymphatic pathway through the right hemidiaphragm could have been stopped by pleural sequelae from right lobectomy. In the other case, a right pleural effusion occurred after peritoneal dialysis. It is a well known pathological entity: the structural defect can be observed by separation of collagen bundles in the tendinous diaphragm. This type of pleuro-peritoneal communication is well known in women suffering from menstrual pneumothorax or in patients treated by peritoneal dialysis. PMID- 1288392 TI - [Disorders of relaxation of the lower esophageal sphincter appearing after resection of a mid-thoracic esophageal pulsion diverticulum]. AB - A pulsion diverticulum of the mid-thoracic oesophagus was resected because of severe dysphagia. A subdiverticular myotomy was associated for the treatment of non-propagated oesophageal contractions, without oesophageal low-sphincter abnormalities. Three months post-operatively, the dysphagia was still present and manometry showed the absence of lower sphincter relaxation after 45 percent of deglutitions; a lower oesophageal sphincter myotomy was performed, resulting in correction of the dysphagia and of the sphincter relaxation abnormalities. The deficit of the inhibitory nervous mechanism, responsible for abnormalities of lower oesophageal sphincter relaxation, was present in the entire intramural oesophageal plexus, but, was not symptomatic at the level of the IOS prior to resection of the diverticulum. PMID- 1288394 TI - [Post-traumatic retroligamentous pneumatocele. Apropos of a case]. PMID- 1288395 TI - [Thymus in posterior mediastinal localization. Apropos of a case in a child]. AB - Posterior and upper mediastinal localization of the thymus gland is uncommon in young children. Presenting symptoms and signs are very variable from incidental diagnosis to bronchopneumonial with atelectasias of the left upper Chest X-Ray and CT Scan are sufficient to make the diagnosis. Treatment of complicated forms with bronchial compression requires thoracotomy and surgical excision. PMID- 1288396 TI - [Is ex situ surgery of the liver useful for difficult hepatic resections?]. AB - Five cases of hepatic tumor deemed unresectable by conventional techniques are presented to illustrate the potential benefit offered by complete hepatic vascular exclusion (Pringle maneuver associated with inferior vena cava clamping below and above the liver). The most extensive and difficult liver resections may be achieved, with possible venous reconstruction, if the clamping period is not interrupted. Hepatic vascular exclusion may exceed one hour, up to 85 minutes in this series, with a good liver tolerance, in the absence of preoperative liver dysfunction. The advantages and disadvantages of the ex situ extracorporeal liver resections performed under similar circumstances are discussed. The authors consider that the role of ex situ liver procedures should be very limited. PMID- 1288397 TI - [Primary colonic intussusception protruding from the anus in adults. Two cases]. AB - The authors report two cases of colonic intussusception in the adult protruding from the anus--or colon-anal intussusception--, not due to a tumor. The first case was a chronic ileo-caeco-colique intussusception, the second case was an acute colo-rectal intussusception. Colo-anal intussusceptions are very rare: less than twenty cases have been described since 1925 in adults. The absence of a tumor origin in our cases represents a special feature, as only three other similar cases have been described. The surgical treatment in both cases was primary colonic resection without colostomy. The surgical treatment of the first case was subtotal colectomy with ileo-rectal anastomosis. The second case was primarily reduced by barium enema which allowed optimal secondary surgical resection of a prepared colon. PMID- 1288398 TI - [Radiological anatomy of the wrist]. AB - The wrist is an articular complex composed of the radio-carpal, distal radio ulnar and all of the carpal joints. Despite progress in imaging techniques, conventional radiology with plain x-rays and arthrography are still very widely used. Plain x-rays, numerous because of the anatomical complexity of the wrist, must be selected in relation to the clinical context and suspected diagnosis and must be performed according to a perfect technique. Contrast arthrography may be uni-, bi-, or tri-compartmental depending on the information required. It allows assessment of the integrity of the intra-articular synovial and ligamentous structures. The specific indications for computed tomography are uncommon, but those of MRI are becoming increasingly frequent due to refinement of the machines, especially the development of surface coils. PMID- 1288399 TI - [Arthrography of the wrist]. AB - The procedure, followed by the normal radiological anatomy of the various joint compartments of the wrist are described. The main indications (especially post traumatic indications) and abnormal findings are then investigated. PMID- 1288400 TI - [MRI of the wrist joint]. AB - Due to the development of new surface coils and the use of thin slices, MRI has become an essential diagnostic tool in wrist pathology. After several technical considerations, the authors describe the normal MRI appearance of the various anatomical structures of the wrist, particularly the triangular fibrocartilaginous complex of the wrist and the elements of the carpal tunnel. They review the principal indications for MRI: chronic diseases such as carpal tunnel syndrome and traumatic ligamentous and cartilaginous lesions. The bone marrow lesions detected in the presence of occult fractures and osteonecrosis of the lunate or scaphoid are then briefly considered. The diagnostic criteria of median nerve compression (carpal tunnel syndrome) include morphological and signal changes in the nerve, abnormal palmar convexity of the flexor retinaculum and signs of tenosynovitis of the intracarpal flexor tendons. However, in practice, MRI is only useful when there is disagreement between the clinical and EMG findings and in postoperative recurrences, in which case it may reveal insufficient section of the retinaculum or the presence of exuberant postoperative fibrosis responsible for persistent nerve compression. Traumatic tears of the triangular fibrocartilage are characterised by a linear high signal intensity image (on T1 and T2 weighted sequences), usually situated in the periphery of the articular disk. Degenerative lesions tend to be central, within the disk and are frequently observed after the age of 40 years. PMID- 1288401 TI - [Instability of the carpal bones]. AB - The understanding of carpal instability and their radiological signs are based on a knowledge of the anatomy and complex physiology of the wrist. This article successively deals with the physiological anatomy, radiological technique, normal static and dynamic radiological features, radiographic signs of various types of instability and therapeutic principles. PMID- 1288402 TI - [Scaphoid bone]. AB - The scaphoid is the most important carpal bone due to the frequency of its pathological involvement. Two points of radiological anatomy are stressed: the presence of the scaphoid tubercle whose projection gives rise to the scaphoid ring, the solid radio-capitatum ligament which bridges the scaphoid. Scaphoid fracture represents 70% of all carpal bone fractures and its presence must therefore be meticulously investigated on appropriate x-rays or on tomographies or CT scans, rather than by the classical repeat examination a fortnight later. CT provides good analysis of scaphoid fragments when consolidation is delayed (pseudarthrosis), allowing earlier and more justified indications for surgery. The wrist ligaments are poorly visualised by MRI at the present time; but it allows study of the cartilage and, most importantly, is a decisive examination when there is a doubt about bone vitality. PMID- 1288403 TI - [Kienbock's disease. Current data]. AB - Aseptic osteonecrosis of the lunate bone is a rare disease of unknown aetiology. The mechanical theory of shearing of the lunate underneath the radius is generally accepted, especially in the presence of a short ulna, even if it is insufficient. The diagnosis is exclusively radiographic and requires, in the early stages, the use of MRI which is more sensitive and specific than bone scan. Plain X-rays allow the disease to be classified into various stages, which determine the therapeutic indications. Many treatments have been proposed, but the follow-up is often inadequate. Simple immobilization is atraumatic, but its efficacy is highly controversial. Equalization of the two bones, usually by shortening the radius, is the most widely used technique and, with a follow-up of more than 20 years, appears to be effective in 80% of subjects. Revascularization of the lunate has been proposed in the early forms. Partial arthrodeses are indicated in the advanced forms. Radio-carpal arthrodesis or denervation of the wrist are indicated in the presence of osteoarthritis. Functional sequelae are frequent in these young subjects, who are often manual workers. PMID- 1288404 TI - [Distal radio-ulnar joint. Traumatic and degenerative diseases]. AB - The distal radio-ulnar joint participates in the biomechanics of the wrist both by transmission of carpal stresses and by its role in the mobility of the wrist. Fractures of the distal radio-ulnar joint are often missed as they are frequently only a radiation of fractures of the radius to the distal radio-ulnar joint. Computed tomography is the most useful examination to assess the severity of these lesions. Distal radio-ulnar dislocations may also be associated with fractures of the radius, but usually occur in isolation. The diagnosis is difficult, as the slightest rotation on plain X-rays interferes with the evaluation criteria. A CT scan in the neutral position and in pronation and supination is the examination of choice for dislocations and subluxations, but must be interpreted according to strict criteria. In contrast, a tea of the triangular ligament can only be assessed on arthrography and the distinction between traumatic and degenerative rupture is difficult. The patient's age, the site of the perforation and the length of the ulna are important elements in the diagnostic decision. MRI appears to be a promising examination for investigation of this joint, but the quality of the images is not yet perfectly reproducible. PMID- 1288405 TI - [Rheumatic wrist]. AB - The wrist is frequently involved in the course of inflammatory rheumatism. The clinical and radiological features of the arthritis may guide the diagnosis when wrist involvement is isolated. The rheumatoid wrist may associate articular and tendon sheath synovitis, nerve compressions, muscle atrophy and deformities. X rays reveal increased volume of the soft tissues, followed by cartilaginous destruction. Magnetic resonance imaging may detect the lesions early in their course. RS3PE, rheumatoid arthritis of the elderly, never induces destructive lesions. Still's disease is distinguished from rheumatoid arthritis by the predominant involvement of the radiocarpal and intercarpal joints with relative sparing of the metacarpo-phalangeal and proximal interphalangeal joints. Jaccoud's hand may be observed in the course of lupus with metacarpo-phalangeal dislocation of capsulo-ligamentous origin without cartilaginous destruction. Wrist involvement is often asymmetrical in ankylosing spondylitis. In psoriatic rheumatism, arthritis of the wrist is similar to that observed in rheumatoid arthritis, but demineralization is less common and occurs later and constructive lesions are associated with pinching. PMID- 1288406 TI - New alcohol resistant strains of Saccharomyces cerevisiae species for potable alcohol production using molasse. AB - Two alcohol resistant strains of Saccharomyces cerevisiae species were isolated from a Greek vineyard plantation. The strain AXAZ-1 gave a concentration of 17.6% v/v alcohol and AXAZ-2 16.5%, when musts from raisin and sultana grapes, respectively, were employed in alcoholic fermentations. They were found to be more alcohol tolerant and fermentative in the fermentation of molasse than the traditional baker's yeast. Specifically, using an initial [symbol: see text] Be density of 16 [symbol: see text] Be at the repeated batch fermentation process, in the first as well as fourth batch, the better AXAZ-1 gave final [symbol: see text] Be densities of 6.0 and 10.5 respectively, and the baker's yeast 11.6 and 14.5. PMID- 1288407 TI - Effect of mixture of surfactants and adsorbents on anaerobic digestion of water hyacinth-cattle dung. AB - In an effort to improve the anaerobic digestion of water hyacinth-cattle dung with enriched methane content, the effects of mixtures of surfactant-surfactant, adsorbent-adsorbent and surfactant-adsorbent have been studied in various combinations. Among the combinations tested, bentonite and gelatin, gelatin and Tegoprens 43, sodium lauryl sulfate and Tegoprens 42, and Tegoprens 47 and Tegoprens 63 showed more than a 100% increase in gas production with higher methane yield. PMID- 1288408 TI - Purification and characterization of lamb pregastric lipase. AB - Lamb pregastric lipase was purified from a commercial source using delipidation, solubilization with KSCN, acid-precipitation, pepsin-digestion, affinity chromatography with agarose-Cibacron Blue F3GA, gel filtration, and elution from a native 10% (w/v) polyacrylamide gel. The enzyme had a single subunit of 68,000 Da with maximum esterase activity when measured at pH 6.0 and 30 degrees C. The enzyme preferentially hydrolyzed short- and medium-chain (C4, C6, and C8) synthetic esters and short-chain (C4 and C6) monoacid triglycerides. The NH2 terminal sequence demonstrated high homology with gastric and lingual lipases. PMID- 1288409 TI - A biosensor for L-proline determination by use of immobilized microbial cells. AB - A biosensor to quantify L-proline within 10(-5)-10(-3) mole/L concentration is described. Immobilized Pseudomonas sp. cells grown in a medium containing L proline as the only source of carbon and nitrogen were used to create the biosensor. The cells oxidized L-proline specifically consuming O2 and did not react with other amino acids and sugars. The change in oxygen concentration was detected with a Clark oxygen membrane electrode. The cells were immobilized by entrapment in polyvinyl alcohol (PVA) cryogel. The resultant biocatalyst had a high mechanical strength and retained its L-proline-oxidizing ability for at least two months. PMID- 1288411 TI - Ethanol production from cellulose by coupled saccharification/fermentation using Saccharomyces cerevisiae and cellulase complex from Sclerotium rolfsii UV-8 mutant. AB - Using cellulase/hemicellulase complex of Sclerotium rolfsii UV-8 mutant and Saccharomyces cerevisiae for fermentation, the coupled saccharification/fermentation (CSF) of 15% AT-rice straw was carried out at 40 degrees C, pH 4.5 for the first 24 h and further incubation was performed at 30 degrees C for 72 h. Increasing the amount of cellulase activity from 3-12 IU FPA/g of substrate resulted in increased yields of ethanol from 1.5-3.6% in 96 h. It has been observed that the coupled system was advantageous over the two stage (separate hydrolysis/fermentation) system as it produced higher amounts of ethanol from cellulose (3.6% as compared to 2.3% ethanol from rice straw). PMID- 1288410 TI - A biocompatible needle-type glucose sensor based on platinum-electroplated carbon electrode. AB - A biocompatible needle-type glucose sensor with a 3-electrode configuration was constructed. A platinum-electroplated carbon stick was used as the working electrode, Ag/AgCl as the reference electrode, and a disposable hypodermic needle made of stainless steel as the counter electrode. A Nafion membrane, an immobilized glucose oxidase (GOD) membrane, and a biocompatible membrane with diffusion-limiting effect were coated successively onto the working electrode. The sensor showed a rapid response (< 120 s in batch operation), good reproducibility (RE < 3%), good stability (over 36 h in control serum), a wide dynamic range (5-600 mg/dL glucose), and superior biocompatibility. It was used to determine glucose in serum. The data obtained from the sensor showed good agreement with that from a clinical autoanalyzer (R > 0.95). PMID- 1288413 TI - Protection of Aspergillus niger cellulases by urea during growth on glucose or glycerol supplemented media. AB - The cellulase enzymes of Aspergillus niger were found to undergo catabolite repression in the presence of glucose and glycerol accompanied by sudden drop in pH of the fermentation medium below 2.0. This sudden drop in pH caused inactivation of cellulolytic enzymes produced by Aspergillus niger. The supplementation of nitrogen sources, especially urea, protects A. niger cellulases from inactivation caused by a sudden drop in pH, since urea helped to maintain the pH of the fermentation medium between 3.5 and 4.5. The role of urea in the protection of cellulase was more prominent when it was used in combination with glycerol (5%). PMID- 1288412 TI - Effects of potassium on the ethanol production rate of Saccharomyces cerevisiae carrying the plasmid pCYG4 related with ammonia assimilation. AB - The influence of potassium on ethanol production by Saccharomyces cerevisiae wild type and AR5 cells carrying the plasmid pCYG4 was investigated. This plasmid carries the glutamate dehydrogenase gene conferring an 11-fold higher level of expressed enzyme activity over the wild type cells. All experiments were carried out in batch culture with medium supplemented to different potassium concentrations up to 180 mM. Maximum ethanol production rate was observed in the AR5 cells grown in medium supplemented with 3.5 mM of potassium ions. Glucose uptake rate increased with increasing potassium up to 60 mM, but higher concentrations depressed glucose uptake rate in both strains. Furthermore, the wild type cells showed higher growth rate, ethanol production, and glucose consumption rate than the AR5 cells. These lower rates in the AR5 cells could be explained by repression of potassium uptake by an enhancement of ammonium feeding, and greater energy requirements by these cells due the presence of the plasmid. PMID- 1288414 TI - Adsorption of phenylalanine from casein hydrolysates. AB - The specific diet therapy for phenylalaninemies requires special hydrolysates of proteins where phenylalanine content is reduced to approx 0.53% of the amino acids present. In previous work, Amberlite XAD-4 resin was used to retain phenylalanine from an acid hydrolysate of casein. It was also observed that the adsorption isotherm of phenylalanine on the resin showed a convex pattern that allowed a frontal chromatography. In the present study, this technique was improved, aiming at the processing of larger hydrolysates volumes. This was achieved with the use of two sequential columns (50 x 1 cm), each containing 34 cm3 of the resin, and joined through a 1-cm long tygon, tube 1 mm diameter. This system was used to process 100 mL of casein acid hydrolysate containing 12 g of free amino acid and allowed the reduction of phenylalanine content from 4.39 to 0.14% of the total amino acids present, within 1 h. It was also observed that this technique could not be directly applied to enzymatic hydrolysates of casein unless they were especially produced for this purpose, which means that in this kind of hydrolysate, phenylalanine should be free or linked in small adsorptive peptides. PMID- 1288415 TI - Protoplast fusion of beta-glucosidase-producing Aspergillus niger strains. AB - Protoplast fusion, induced by polyethylene glycol and Ca2+, was carried out between two auxotrophic strains of Aspergillus niger. The fusion frequency ranged from 6.2 x 10(-2) - 9.1 x 10(-2). After induced haploidization of a diploid, various segregants showing combinations of the parental genetic markers were isolated. Unlike diploids, haploid segregants exhibited greater variations in their morphology and beta-glucosidase activities. One segregant showed a 2.5-fold increase in beta-glucosidase activity over those of the parents. Thus, this method appears promising for creating new recombinant strains of A. niger with improved beta-glucosidase activities. PMID- 1288416 TI - Synergism between Clostridium thermocellum cellulases cloned in Escherichia coli. AB - We have obtained a synergistic effect during degradation of Avicel and filter paper by Clostridium thermocellum cellulases (two endoglucanases and one cellobiohydrolase) cloned in Escherichia coli. The highest degree of synergism was found at early stages of reaction, during the first 20 h: 2.5 and 2.9 on Avicel and filter paper, respectively. During combined action of all three cellulases the main product is cellobiose. PMID- 1288418 TI - Epidermal expression of the calcium binding surface antigen 27E10 in inflammatory skin diseases. AB - The expression of the heterodimeric complex of the calcium-binding proteins MRP-8 and MRP-14 was investigated in various inflammatory dermatoses using immunohistochemical staining with the monoclonal antibody 27E10. In addition to the inflammatory infiltrate, a positive staining was repeatedly found in the involved epidermis from patients with lichen planus, lupus erythematosus and psoriasis vulgaris, but not in normal skin epidermis and/or in epidermis from leucocytoclastic vasculitis patients. The keratinocytic expression of the 27E10 antigen was dissimilar to that of the MHC class-II molecules and the adhesion molecule ICAM-1. These data indicate that the 27E10 antigen is a distinct activation marker of inflammatory keratinocytes and may have proinflammatory properties. PMID- 1288417 TI - Purification and characterization of a cystatin-type cysteine proteinase inhibitor in the human hair shaft. AB - We found a cysteine proteinase inhibitor in human hair shaft extract treated with 0.01 M Tris HCl buffer, pH 8.0. A yield of 0.2 mg of purified cysteine proteinase inhibitor was obtained from 86 g of hair shaft. The cysteine proteinase inhibitor had a molecular mass of 13 kDa as determined by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was more stable to heat and pH than most proteins and had a pI of 4.7. Immunologically, its antigenicity was the same as that of cystatin A, but differed from that of cystatin B and C, and kininogen. The amino-acid sequence of the first 30 residues from the NH terminus of the inhibitor was identical to that of cystatin A from human epidermis. Hair shaft cysteine proteinase inhibitor is thus considered to be identical to epidermal cystatin A. PMID- 1288419 TI - Clinical evaluation of scleroderma spectrum disorders using a points system. AB - We have established a new diagnostic method using a points system to evaluate patients with early scleroderma and those with scleroderma spectrum disorders (SSD). To examine the clinical usefulness of this method, it was applied to a total of 215 cases including 97 patients with scleroderma, 32 with SSD, 28 with presumed primary Raynaud's phenomenon (RP) and 58 with other connective tissue disorders (CTD). A total score was obtained for each patient as the sum of the following five factors: (1) extent of skin sclerosis (maximum, 10 points); (2) pulmonary changes (maximum, 4 points); (3) antinuclear antibodies (maximum, 5 points); (4) pattern of Raynaud's phenomenon (maximum, 3 points); and (5) nailfold bleeding (maximum, 2 points). Of the 97 scleroderma patients, 86 (89%) had 9 or more points, and of the 32 SSD patients, 28 (88%) had 5 to 8 points. In contrast, all patients with presumed primary RP and 54 of 58 (93%) patients with other CTD had 0 to 4 points. These data suggest that this diagnostic method is very useful not only for clinical evaluation of SSD, but also for the differentiation of scleroderma and SSD from other CTD and primary RP. PMID- 1288420 TI - Anticentromere-protein-B--DNA complex activities in anticentromere antibody positive patients. AB - Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often those with scleroderma). In this study, we analysed activities of anti-CENP-B-DNA complex in anticentromere antibody (ACA)-positive patients using DNA immunoprecipitation with purified CENP B. The activities correlated with ACA titres and were closely associated with Raynaud's phenomenon. Patients with CREST symptoms (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) showed higher activities than those with no symptoms. Our results suggest that autoimmune responses to native CENP-B may have an important role in the pathogenesis of scleroderma. PMID- 1288421 TI - Biochemical responses of skin to allergenic and non-allergenic nitrohalobenzenes. Evidence that an NADPH-dependent reductase in skin may act as a prohapten activating enzyme. AB - Using a selection of 'classic' haptens (dinitrohalobenzenes and picryl chloride) and related non-sensitizing analogous, we examined changes in levels of glutathione (GSH) and glutathione disulphide (GSSG) in mouse skin 12 h after their epicutaneous application. We observed that elevation of GSSG levels and/or depletion of GSH levels correlated well with contact allergenic potential. Non sensitizing analogous failed to perturb GSH/GSSG status. In vitro assays using mouse skin and rat liver microsomal preparations indicated that only the allergenic nitrohalobenzenes initiated NADPH-dependent oxygen utilization, with the activity falling off in the order picryl chloride >> DNIB > DNBB > DNCB > DNFB. In addition, an examination of the colour of mouse skin homogenates ex vivo after application of the dinitrohalobenzenes showed significant yellowing (consistent with aromatic nucleophilic substitution) only with DNFB. Our results indicate that, while an aromatic nucleophilic substitution reaction with skin protein can possibly account for the allergenicity of DNFB, it does not seem to occur with DNCB, DNBB or DNIB. These may instead behave mainly as prohaptens which are activated enzymically by NADPH-dependent reductase(s) within the skin, with the concomitant generation of superoxide and hydrogen peroxide, to form potentially protein-reactive free radical and other metabolites. Picryl chloride appears capable of both conjugating directly with proteins by aromatic nucleophilic substitution and undergoing NADPH-dependent metabolism to other potentially protein-reactive metabolites. PMID- 1288422 TI - Rosin allergy: identification of a dehydroabietic acid peroxide with allergenic properties. AB - A peroxide of dehydroabietic acid was isolated from rosin using flash chromatography and preparative HPLC. It was identified by 1H-NMR and MS. In animal experiments, this peroxide cross-reacted with a previously identified allergen in rosin, 15-hydroperoxyabietic acid (15-HPA), despite differences in molecular weight and unsaturation. Both substances are able to react via a radical mechanism generating structurally similar molecules. In patch testing of patients, no reactions were observed to the peroxide. Low skin penetration of the peroxide could be the explanation for this. The peroxide seems of little clinical importance. The observed cross-reactivity is an indication of antigen generation via a radical mechanism. Only a few compounds that react with radical mechanisms to form antigens are described in the literature. PMID- 1288423 TI - Effects of thermal shocks on interleukin-1 levels and heat shock protein 72 (HSP72) expression in normal human keratinocytes. AB - Interleukin-1 expression is reported to be modified under a number of cell conditions including physiological stress, injury and activation. We report the effects of the physiological stresses cold and heat shock on IL-1 levels in keratinocytes. Having observed that normal human skin obtained from plastic surgery, usually stored at 4 degrees C for a few hours, highly expressed HSP72, a constant feature of stressed human keratinocytes, we wondered whether this induction could be linked to a cold shock and to modification of IL-1 levels in keratinocytes. Cultured keratinocytes were incubated at 4, 37, 40 and 43 degrees C for 1.5, 4, 8 and 16 h in a defined medium. HSP72 expression was studied by immunohistochemistry and immunoblot and IL-1 was quantified using specific and sensitive radioimmunoassay. Our findings showed that intracellular IL-1 alpha and IL-1 beta levels are not significantly modified by thermal shock. HSP72 is only induced after cell exposure to 43 degrees C and is not a cold-shock protein. These results demonstrate that thermal stress is not an inductive signal for IL-1 modification in keratinocytes. PMID- 1288424 TI - Retinoic acid provokes a regeneration-like proliferative response in murine epidermis. A bivariate DNA/bromodeoxyuridine flow cytometric study. AB - Retinoic acid (RA) is an inducer of epidermal proliferation by a mechanism of action which is not fully known. We examined the proliferative response of hairless mouse epidermis to a single topical application of different doses of RA (0.1-1000 nmol). The mitotic rate was assessed using the stathmokinetic method, and change in epidermal cell numbers were scored per microscopic vision field in tissue sections. Cell cycle parameters were measured by bivariate bromodeoxyuridine/DNA flow cytometry on isolated epidermal basal cells after pulse labelling up to 10 days after RA treatment. The results showed a dose dependent increase in mitotic activity with a maximum at 3 days after RA application, and a dose-dependent hyperplasia with a maximum at 4 days after RA application. Cell-cycle analysis showed an immediate proliferative response after RA application similar to that following various skin irritants. Although differences in the G2 phase transit were seen, this indicates a similar mechanism of action of RA-induced epidermal proliferation and that associated with epidermal regeneration in general. PMID- 1288425 TI - In vitro activity of pyronaridine against African strains of Plasmodium falciparum. AB - The in vitro activity of pyronaridine was determined and compared with the activity of monodesethylamodiaquine and amopyroquine against 31 clinical isolates and two clones of Plasmodium falciparum originating from Central and West Africa using a semi-micro drug susceptibility test. Pyronaridine and amopyroquine were 2.5 and four times less active, respectively, against the highly chloroquine resistant clone, than against the chloroquine-susceptible clone but were equally active against chloroquine-susceptible and chloroquine-resistant clinical isolates. Compared with chloroquine-susceptible isolates, monodesethylamodiaquine was three times less active against chloroquine-resistant parasites. Pyronaridine is highly active against chloroquine-resistant strains of P. falciparum and may be a promising candidate for the treatment of resistant malaria. PMID- 1288427 TI - Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro. AB - Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug resistant cells reverse chloroquine resistance in vitro. Hence, the co administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally induced chloroquine-resistant Plasmodium falciparum parasitaemias. PMID- 1288426 TI - The chemotherapy of rodent malaria. XLVII. Studies on pyronaridine and other Mannich base antimalarials. AB - The activities of Mannich base antimalarials, including pyronaridine, have been explored against drug-sensitive (Plasmodium berghei N) and chloroquine-resistant (Plasmodium yoelii NS) rodent malaria parasites in vivo. Lines of these parasites have been developed with resistance to pyronaridine, amodiaquine, or WR 228,258. The responses and patterns of cross-resistance of these lines to Mannich bases and other blood schizontocides are inconsistent. It is concluded that some Mannich bases may prove still to be of value inthe treatment of chloroquine resistant Plasmodium falciparum infection. PMID- 1288428 TI - Complement (C3) levels and activation in rabbits experimentally infected with Trypanosoma evansi. AB - Rocket immunoelectrophoresis was used to monitor the levels of the third complement component (C3) in the blood of rabbits experimentally infected with Trypanosoma evansi. Although a reduction in the circulating levels of C3 was associated with C3 activation in rabbits with high levels of parasitaemia, there was no evidence for C3 activation in uninfected rabbits, rabbits with early stage, light infections or rabbits cleared of infection by drug treatment. Host tolerance to current infection and to re-exposure to the parasite are probably affected by such changes in C3. PMID- 1288429 TI - Visceral leishmaniasis in southern Sudan: status of healthy villagers in epidemic conditions. AB - A combination of interview, serology and skin testing was used to investigate the status of apparently healthy villagers during a visceral leishmaniasis epidemic in southern Sudan. The number of people who had died equalled the number who were alive at the time of the survey. The direct agglutination test (DAT) identified 10% of the people as being serologically positive. Most young children (36/39) and 34% (22/64) of adults had neither positive serology nor skin test. About 64% (42/66) of adults had positive skin tests. In two villages, 54% and 76% of those over four years of age showed evidence of having been infected. The mortality associated with infection was estimated as at least 69%; 25% of those infected appeared to have cured spontaneously. The outcome for the remaining 6% was still doubtful. Even in this devastating epidemic there is, therefore, evidence of a considerable amount of infection without severe disease. Serological tests, while useful clinically, are apparently not useful for detecting early cases. Combined skin testing and serology produces a comprehensive though partially hypothetical picture. PMID- 1288430 TI - Axenic cultivation of amastigotes of Leishmania donovani and Leishmania major and their infectivity. AB - Two clones of promastigotes, one of Leishmania donovani and one of L. major, and an uncloned stock of L. major were axenically transformed to heat-shock amastigotes, at 35 and 37 degrees C, respectively. Of the four different culture media tested, a relatively cheap, liquid medium, RBLM, was found to be the best, both for the transformation of the promastigotes and the serial, axenic cultivation of the amastigotes. In an experiment of 30 days duration, serial cultivation, in an atmosphere with 5% CO2, was possible by subculturing every three days. There were significant differences in virulence in BALB/c mice between axenically-cultured amastigotes and promastigotes, both in terms of the weights, lengths and parasite burdens of the spleens of mice infected intraperitoneally (ip) with L. donovani or L. major and of the appearance, type and size of the cutaneous lesions which developed in mice given L. major by intradermal inoculation. PMID- 1288431 TI - Analysis of host components in hydatid cyst fluid and immunoblot diagnosis of human Echinococcus granulosus infection. AB - To improve serodiagnosis of cystic hydatidosis, immunoblotting studies were performed to look for a highly specific parasite antigen(s). First, commercially available hydatid cyst fluid antigen preparations were characterized by SDS-PAGE and by immunoblotting with sera specific for parasite and host animal proteins. One preparation, designed for use in complement fixation tests, did not appear to be suitable for immunoblotting because of the low concentrations of parasite antigens. Several host proteins, including serum albumin and IgG, were detected in the cyst fluid. Sera from patients with Echinococcus granulosus infections and other parasitic diseases were examined by immunoblotting for antibodies against specific cyst fluid parasite antigens. Several parasite antigens were variably recognized. Only one antigen, a 40 kDa protein, was recognized by all E. granulosus-infected patients. Reactivity against this antigen was also observed in all sera from E. multilocularis, cysticercosis, and schistosomiasis patients as well as in some filariasis cases. Two E. granulosus antigens, molecules of 12.5 and approximately 17 kDa, were only recognized by antibodies from some E. granulosus patients. PMID- 1288432 TI - Evaluation of hepatic fibrosis after oxamniquine therapy of murine schistosomiasis. AB - Chemical and histological indices of liver fibrosis were measured after eight, 18 and 28 weeks in mice infected with Schistosoma mansoni and treated at eight weeks with oxamniquine, in mice infected with S. mansoni and not treated and in mice not infected with S. mansoni. Total worm burdens and liver egg counts were determined in the infected mice to determine severity of infection. Treatment with oxamniquine resulted in near total eradication of S. mansoni worms after 10 weeks and in their complete killing and marked reduction of eggs in the liver at 10 and 20 weeks. Liver fibrosis 10 weeks after oxamniquine treatment was not significantly different than in the untreated, infected group but there was no progression between 10 and 20 weeks after oxamniquine treatment. Fibrosis did however increase between 10 and 20 weeks in the untreated infected group. In the murine model, oxamniquine is an effective treatment for S. mansoni and prevents progression of liver fibrosis. PMID- 1288433 TI - Observations on Culex quinquefasciatus Say in relation to transmission of filariasis due to subperiodic Wuchereria bancrofti in Samoa. AB - Observations on Culex quinquefasciatus Say in Samoa during a study of the epidemiology and control of subperiodic bancroftian filariasis are reported. The man-biting rate of C. quinquefasciatus was comparable with that of Aedes (Finlaya) samoanus Gruenberg in one indicator village and lower in another. The house-frequenting behaviour of the two species was similar. Culex quinquefasciatus was active throughout the night with peak biting during midnight hours, and its survivorship, estimated by two methods, was higher than those of the main vectors, A. (Stegomyia) polynesiensis Marks and A. samoanus. Culex quinquefasciatus showed low susceptibility to subperiodic Wuchereria bancrofti, compared with the two main vectors, in laboratory feeding experiments on volunteers with three levels of microfilaraemia. This agrees with the observed very low natural infection rate, suggesting that C. quinquefasciatus is an inefficient vector of subperiodic W. bancrofti in Samoa. PMID- 1288434 TI - The diel pattern of entry to outdoor oviposition sites by female Aedes aegypti (L.) (Diptera: Culicidae) that then laid eggs there: a preliminary study. AB - Experimental observations, made outdoors during the dry and wet seasons in Trinidad, demonstrate that more than 70% of female Aedes aegypti that are destined to oviposit within the next two hours enter ovitraps during the first and last two-hour periods in the day, a finding consistent with the diel pattern of oviposition recorded earlier at the same site. It is possible that proportionately more eggs are laid in the morning peak during the dry season than the wet season. Fewer eggs are laid within a two-hour experimental period if an open ovitrap is not accessible to females before the experimental period begins. It is inferred that, during the early afternoon, ovitraps are entered by females destined to lay eggs there more than two hours later in the same day. PMID- 1288435 TI - The nature of the teneral state in Glossina and its role in the acquisition of trypanosome infection in tsetse. AB - Teneral Glossina morsitans morsitans from outbred and susceptible stocks infected with Trypanosoma (Nannomonas) congolense developed, respectively, three and six times higher midgut infection rates than flies of the same stock which had previously taken a bloodmeal. Non-teneral G. m. morsitans remained relatively refractory to infection when infected at subsequent feeds. Differences in susceptibility to midgut infection between teneral flies from susceptible and outbred lines of G. m. morsitans disappeared in non-teneral flies, showing that maternally inherited susceptibility to midgut infection is a phenomenon restricted to the teneral state of the fly. Laboratory reared G. m. morsitans were found to have become significantly more susceptible to trypanosome infection than wild flies from the population from which the colony was derived. The likely role of rickettsia-like organisms (RLO) in potentiating teneral susceptibility to midgut infection is discussed. The addition of the specific midgut lectin inhibitor D-glucosamine to the infective feed of non-teneral flies increased midgut infection rates to levels comparable with those achieved in teneral flies. It is concluded that the peritrophic membrane does not act as a barrier preventing non-teneral flies becoming infected. The relative refractoriness of non-teneral flies suggests that they do not play a significant part in the epidemiology of Trypanozoon or T. congolense infections. PMID- 1288436 TI - A survey of mites on farm animals in Libya. AB - In 1985-1988, 2287 farm animals (cattle, camels, sheep, goats, horses, donkeys, dogs and rabbits) suspected of carrying parasitic mites were examined at 58 farms throughout Libya. Mites were identified on 1303 of these animals. The commonest parasites on cattle were Psoroptes and Chorioptes, on camels and sheep were Sarcoptes and Psoroptes, and on goats were Sarcoptes and Demodex. Infested horses carrier Psoroptes or Chorioptes, and one donkey carried Sarcoptes. Otodectes was common on dogs, but Sarcoptes was rare and no Demodex were seen. Rabbits often had psoroptic ear mange or sarcoptic body mange. Dermanyssus gallinae and Ornithonyssus bursa were seen on chickens, but no mites were found on pigeons, ducks or turkeys. PMID- 1288437 TI - A survey of ticks on farm animals in Libya. AB - Thirteen species of ixodid ticks and two species of argasid ticks were collected during a three-year survey of 58 farms in Libya. These included Boophilus annulatus, B. microplus, B. decoloratus, seven species of Hyalomma, Rhipicephalus sanguineus, Rh. evertsi, Rh. bursa, Argas persicus and Ornithodoros foleyi. This is the first recording of B. microplus, B. decoloratus and Rh. bursa in Libya. Of 20,391 animals examined by random sampling, 2020 (9.6%) had ticks; particularly common were Hy. dromedarii on camels, Hy. impeltatum on sheep and Hy. excavatum on cattle. The tick found most frequently overall was Hy. dromedarii. PMID- 1288438 TI - Prothrombin and factor X activating properties of Bothrops erythromelas venom. AB - The enzymatic properties of Factor II (FII) and Factor X (FX) activators from Bothrops erythromelas venom were investigated. Both activators were inhibited by ethylenediaminetetraacetate (EDTA) and 1,10-phenanthroline, and are thought to be metalloproteinases with molecular weights of 90 kDa and 70-90 kDa, respectively. The activity of the FII activator in the crude venom was about 30 times greater than that in Oxyuranus scutellatus venom and the level of FX activator activity, which was CA2+ ion dependent, was similar to that in Daboia russelli venom. The venom also had two haemorrhagic factors (58 and 105 kDa) and two fibrinolytic enzymes (18 and 58 kDa). PMID- 1288439 TI - The effect of exposure to selected numbers of Schistosoma mansoni miracidia on survival of cohorts of Biomphalaria pfeifferi. AB - Cohorts of 25 specimens of Biomphalaria pfeifferi were each exposed to batches of one, three, five, seven and 10 Schistosoma mansoni miracidia per snail. The effect on survival was evaluated by calculating the weekly per capita mortality rates and the mean life expectancy of the exposed snails. No statistically significant difference could be demonstrated between the mean per capita mortality rates of cohorts exposed to one and three miracidia per snail. Likewise there was no significant difference between the values obtained for cohorts exposed to five, seven and 10 miracidia per snail. In general, however, survival of the cohorts showed an inverse relationship with the number of miracidia to which each individual snail was exposed. PMID- 1288440 TI - Plasma lactate dehydrogenase estimation in the diagnosis of malaria. PMID- 1288441 TI - Sero-epidemiological survey for Chagas' disease among the Xavante Indians of central Brazil. PMID- 1288442 TI - An attempt to establish Helisoma duryi, a possible competitor of intermediate snail hosts of schistosomiasis, in natural habitats in South Africa. PMID- 1288443 TI - Human articular cartilage in osteoarthrosis. I. The matrix. Transmission electron microscopic study. AB - The present research has been carried out with the aim of contributing to the understanding of morphological changes in human articular cartilage during osteoarthrosis and to evaluate the usefulness of TEM in this application. Only the matrix was examined in this first phase of study. Fragments from the femoral head of 20 patients subjected total hip arthroplasis, were studied by TEM after treatment with current procedures. The images obtained were considered observing the division of cartilage into superficial, intermediate and deep layers. Patients were divided according to the gravity of their clinical conditions. The least severe forms of pathology seem to involve only the superficial layer, which quickly loses the lamina splendens and may be affected by rarefactions of the matrix, which becomes fissured, while the deep layers are only slightly involved. During the later stages, the pathology progresses with irregularity of disposition and size of the collagen fibres and an increase in the number and size of fissures. The intermediate layer shows architectural disorder in the collagen fibres, even reaching the deep layer. The interfibrillar distance appears greater. As pathology progresses, the superficial layer tends to disappear, while the successive layers undergo progressive alteration in disposition and size of the collagen fibres. Globular aggregations of various dimensions and electron density similar to collagen are present in the deep layer. PMID- 1288444 TI - The myenteric plexus of the rat colon: a methodological approach for scanning electron microscopical study. AB - In the present research four different procedures were tested for the Scanning Electron Microscopic identification of Auerbach's myenteric plexus in the distal colon of the rat. The specimens were processed as follows: enzymatic and chemical digestion (trypsin and HCl); fixation with glutaraldehyde; fixation and staining with zinc iodide/osmium tetroxide (ZIO); fixation and staining with zinc iodide/osmium tetroxide (ZIO) followed by maceration in NaOH solution. All the procedures required microdissection to separate the different layers of the colonic wall. Light microscopic controls were prepared with the ZIO technique. Among the methods utilized, fixation and staining with ZIO appeared to be by far the best as regards the preservation of the architectural arrangement of the myenteric plexus as well as of the fine structural details. PMID- 1288445 TI - Vasculature of bovine placentas studied by scanning electron microscopy of corrosion casts. AB - Corrosion casts, obtained after injection of Tensol or Mercox, from 10 placentas of Holstein breed cows, were studied. The investigation was performed in fetal cotyledons, which are attached to uterine caruncles to form units, called placentons. Arteries and veins form, together, vascular cylinders, with the venous half cartridge partially surrounding the arterial one. The morphological differences between arterioles and venules concern the type of distribution, branching, surface (nuclei, oblique folds, anular narrowings). PMID- 1288446 TI - Stereology of the pterygopalatine ganglion of the rat. AB - The right pterygopalatine ganglia (PG) of 9 male Wistar-strain rats were dissected, embedded in Epon (3 specimens) or paraffin (6 specimens), and prepared for stereological examination under light microscopy. The perikarya were quantitatively characterized, and the ganglionic volume was determined. Stereology is an efficient method for the quantitative evaluation of the perikarya of the PG. The results(expressed as mean +/- standard deviation) were: a) areal fraction occupied by the perikarya = 53.8 +/- 7.4%; b) the perikaryal surface area per volume = 0.101 +/- 0.013 microns-1; c) the number of perikarya per volume x 10(-5) = 5.26 +/- 0.99 microns-3; d) the mean profile area of the perikarya (apk) = 505.93 +/- 78.29 microns 2; e) the mean perikaryal volume (vpk) = 9,179.33 +/- 1,533.52 microns 3; and f) the ganglionic volume = 0.210 +/- 0.127 mm3. The low coefficient of variation the apk and vpk values suggests the presence of only one population of neurons in the PG of the rat. The number of perikarya in the PG is about 11,046 per ganglion. As compared to analogous data in the otic ganglion of the rat, the PG did not show statistically significant stereological differences, but the relatively higher number of neurons found in the PG is probably associated with the higher functional activity of this ganglion. PMID- 1288447 TI - Endocrinologic effects of the anaesthetic propofol. AB - Because of the similarities of the adrenal glands of mammals and of the lizard Podarcis s. sicula, the latter has already been the subject of various studies on the effects of Propofol and other anaesthetics. Because a relationship between the activities of the thyroid and adrenal glands of this species has been demonstrated, the authors administered Propofol to a species of lizard to investigate its effects on the thyroid gland. Propofol inhibited thyroid activity, promoted steroid synthesis, and caused the contemporaneous appearance of both adrenaline and noradrenaline granules in the cytoplasm of the chromaffin cells. These results suggest that inhibition of the activity of the thyroid gland is secondary to the action of Propofol on the adrenal gland. PMID- 1288448 TI - Quantitative growth of the eye in the human fetus. AB - Eye weight growth was studied in 50 human fetuses aged 14 to 39 weeks after conception. The collected date was correlated with fetal maturity parameters (festational age and fetal weight) using the allometric method. Normal eye weight curves were obtained. The results indicate that eye weight growth present negative allometry. These curves may be important for the diagnosis of fetal eye malformations, and may indicate that noninvasive method such as ultrasounds can be used. PMID- 1288449 TI - [The future of children cured from leukemia]. PMID- 1288450 TI - [Prediction and prevention of type 1 diabetes]. PMID- 1288451 TI - [Liddle syndrome (or pseudo-hyperaldosteronism). Long-term development and erythrocyte potassium flow study in 4 cases]. AB - BACKGROUND: Liddle's syndrome (or pseudoprimary aldosteronism) is a rare hereditary disease; only 18 cases have been reported since 1963. Its cause remains unclear, but one of its features is increased cell membrane permeability to ions. PATIENTS AND METHODS: A diagnosis of Liddle's syndrome was made in 4 new cases, all female, two of them sisters (cases n0 3 and 4), at the ages of 2, 12, 5 and 4 years. The first manifestations were dehydratation with hypokalemia at 6 months (case n0 1), hypertension at 2 years (case n0 2), polydipsia with poor weight and height gain at 5 and 4 years of age (cases n0 3 and 4). At diagnosis, all the patients had severe hypertension, metabolic alkalosis, hypokalemia and hyperkaliuria, low plasma renin activity and serum aldosterone levels. Administration of antihypertensive agents was without effect, but the hypertension was reduced when triamterene and low-sodium diet were used. Hypercalciuria was observed in 2 cases and nephrocalcinosis in 2 (case n0 1 had both hypercalciuria and nephrocalcinosis). The 2 oldest patients (n0 3 and 4) developed progressive kidney failure, possibly due to reno-vascular disease secondary to hypertension. Patient n0 3 underwent kidney transplantation 18 years after the first symptoms of the disease. This resulted in the complete disappearance of her hypokalemia and hypertension. The red blood cell membrane permeability to K+ and Cl- was studied in all 4 cases before triamterene treatment. The passive permeability to K+ and (K+/Cl-) cotransport were both elevated. A second study, 3 years (cases n0 2 and 3) and 8 years (cases n0 1 and 4) later, of patients treated with triamterene showed low values for passive K+ permeability and (K+/Cl-)-cotransport. CONCLUSIONS: The 4 new cases of Liddle's syndrome had the classic features of the disease, except for hypercalciuria and nephrocalcinosis in 2 of them. The cell membrane permeability data are difficult to interpret. Hypokalemia and hypertension were immediately corrected after kidney transplantation in one case and remained so for 4 years, suggesting that this disease is tubular in origin. PMID- 1288452 TI - [Influenza A infection in children. Clinical spectrum and comparison with respiratory syncytial virus infection during the winter 1989-1990]. AB - BACKGROUND: Respiratory syncytial viral (RSV) infection can be rapidly differentiated from influenza viral infection by immunofluorescence techniques. These tests were used to identify some epidemiological and clinical characteristics of both infections. METHODS AND PATIENTS: 77 RSV and 22 influenza viral infections were detected during an outbreak (November 1989 to March 1990) in 210 children less than 6 years admitted for lower respiration tract infections. The fluorescent antibody assay was performed on nasal aspirates. RESULTS: The RSV outbreak ran from November to March, while the influenza outbreak was shorter, during December and January. The patients infected with RSV were younger (mean age: 6.7 months) than those infected with influenza virus (mean age: 20.9 months) (p < 0.001). Those with influenza virus infection presented with higher temperatures, more often had initial seizures (p < 0.05) and displayed fewer clinical or X-ray respiratory symptoms (p < 0.001). Mean durations of hospitalization were 9.9 days for RSV infection and 7.7 days for influenza virus infection. The therapeutic use of bronchial dilators, oxygen and steroids was correlated with the degree and duration of respiratory manifestations. A 3 month follow-up was insufficient to show any difference between recurrences or complications in the two groups. CONCLUSION: The clinical and radiological differences in these two groups of patients viral-infected are similar to those described in the literature. Variability from one outbreak to another precludes any extrapolation to other populations and justifies the systematic use of the fluorescent antibody assay, especially when a specific antiviral therapy is considered. PMID- 1288453 TI - [Phenotypic expression of 12 mutations of the phenylalanine hydroxylase gene]. AB - BACKGROUND: Several mutations in the human phenylalanine hydroxylase (PAH) gene have been described and it may be interesting to tentatively correlate mutant genotypes and clinical phenotypes of phenylketonuria (PKU). METHODS: Twelve mutations were searched for using classical techniques of molecular biology in a total of 126 patients. 3 phenotypes were arbitrarily defined: typical PKU, atypical PKU or Mediterranean form, and persistent mild hyperphenylalaninemia. The patients were classified according to the residual in vivo PAH activity. RESULTS: Mutations were found in 64 patients. One mutation was found in each of the 2 alleles in 20 children. Only one mutation could be identified in the other 44. Only 45 children could be assigned to a phenotype. Mutations leading to total loss of PAH activity were associated with typical PKU (in homozygotes or compound heterozygotes). Mutations leading to residual PAH activity were associated in homozygotes with atypical PKU; they were also associated in compounded heterozygotes with atypical PKU, irrespective of the fact that the other allele suppressed enzyme activity or was unknown. A mutation which changed the affinity of PAH for phenylalanine was associated with mild hyperphenylalaninemia. CONCLUSION: The clinical heterogeneity of PKU can be correlated with identified mutations of the human PAH gene. Molecular studies do not help to predict either the phenotype or the long-term outcome. However, description of the biochemical changes combined with identification of the mutation should lead to a better understanding of consequences of mutation for PAH activity. PMID- 1288454 TI - [Risk factors of sudden infant death and of death by accidents. According to a national survey in the total postneonatal death]. AB - BACKGROUND: The incidence of sudden infant death syndrome (SIDS) peaks at 2-4 month of age and during the colder months of the year. Other risk factors such as sex, birth weight, maternal age and multiple pregnancy also seem to be shared by the other causes of death after the neonatal period. POPULATION AND METHODS: A retrospective, exhaustive survey of all deaths of infants aged 28 days-one year was carried out between September 1986 to December 1987. The control group was a representative sample of the live births in France during 1989. The deaths were classified into 3 groups: group I, 1184 SIDS, group II 228 SIDS remaining unexplained after autopsy (out of 315 autopsied SIDS), and group III 83 accidental deaths. The factors studied were: sex, birth weight, maternal age, number of infants born from the pregnancy. The risk factors were measured by Odds Ratios and the variables related to mortality were introduced into a logistic model. RESULTS: Incidence of deaths peaked between the 2nd and the 4th month of age in groups I and II while deaths were evenly distributed throughout the first year in group III. Colder months, male gender, low birthweight, multiple birth and the young age of the mother all increased the risk of death in SIDS (groups I and II) but the same factors were also linked to accidental deaths. CONCLUSION: The results confirm those of earlier reports and raise the question why the risk factors for accidental deaths are similar to those for explained or unexplained SIDS, except for infant age. PMID- 1288455 TI - [Evaluation of vaccine coverage in children under two years of age in Kinshasa (Zaire)]. AB - BACKGROUND: Despite efforts to make immunization against preventable diseases available to all children in Zaire, only about 33% of the children living at Kinshasa were immunized in 1986. METHODS: The compliance with the vaccination schedules was evaluated in 211 children less than 2 years of age consulting in the largest medical center of Kinshasa during one week in September 1989. Socio demographic data on the parents and histories of infectious preventable diseases in children were also collected. RESULTS: 93% of the children were immunized against tuberculosis, 85% against diphtheria, tetanus, pertussis and poliomyelitis, 76% against measles. Compliance with the vaccination schedule was higher when the mothers were better educated, or when they worked in the public service. 25% of the children had not been immunized against measles at the age of 9 months. CONCLUSION: The vaccine schedule and the strategy must still be improved. PMID- 1288456 TI - [Chronic intestinal pseudo-obstruction and delayed myenteric ganglion cell maturation]. AB - BACKGROUND: Enteric nerve cells begin to mature during the last trimester of pregnancy and become mature only after birth. The degree of maturation seems to be related to bowel motility. CASE REPORT: A girl was born from a pregnancy complicated by hydramnios, and did not pass meconium before the 64th hr of life. Barium enema on day 4 showed a left microcolon with no distension of the transverse colon. Tests for cystic fibrosis were negative. On day 12, the patient presented with septicemia due to Pseudomonas maltophylia. Parenteral alimentation by central catheter was instituted. Surgical rectal biopsy showed that the number of ganglion cells was normal but the cells were immature. Progressive feeding was possible for the 3rd month of life. A second rectal biopsy at 3 1/2 months showed some remaining immature ganglion cells. CONCLUSION: Immature ganglion cells can account for neonatal functional intestinal obstruction, as has been established for the small left colon syndrome. The progressive loss of symptoms seems to be correlated with histological maturation of the neurological apparatus of the large bowel. Severe complications, such as occlusion, sepsis, nutritional disorders can occur during this long period of functional intestinal obstruction. PMID- 1288457 TI - [Systemic gas embolism in the greater circulation in a ventilated premature infant]. AB - BACKGROUND: Pneumothorax is common complication in newborns; its incidence is increased by intubation, particularly when high pressure ventilation is necessary. Systemic air embolism is a rare and usually fatal form of "displaced air". CASE REPORT: A preterm newborn, 27 weeks of gestational age, weighing 940 g, with respiratory distress syndrome was treated by intubation at 1 min of life and high pressure ventilation (Peak 36 cmH2O, PEP 6 cmH2O, FiO2 = 1). Bilateral pulmonary interstitial emphysema was seen on X-rays at 4 hr of life. Acute cyanosis and bradycardia occurred at 7 hr of life; large amounts of air mixed with blood were withdrawn from the umbilical vein catheter. There was no pneumothorax, pneumomediastinum or subcutaneous emphysema. The newborn died at 9 hr of life. Post mortem injection of contrast fluid into umbilical vein catheter indicated no cardiac perforation: this finding was confirmed by autopsy. CONCLUSION: This is a new case of systemic air embolism that may be due to high pressure ventilation in an extremely underweight newborn. Preventive measures consist of monitoring ventilation, possibly using new techniques, but their efficacy remain to be demonstrated. PMID- 1288458 TI - [Amiodarone and fetal supraventricular tachycardia. Apropos of a case with neonatal hypothyroidism]. AB - BACKGROUND: Fetal tachycardia can be a cause of in utero death. Its detection is not always easy and its treatment is still controversial. CASE REPORT: Paroxysms of supraventricular tachycardia were detected on echocardiography at the 25th week of a second pregnancy. The mother was given sotalol, but the supraventricular tachycardia became permanent. At the 27th week of gestation, sotalol was stopped and the mother was given digoxin and the foetus received 2 injections of digoxin, 10 micrograms/kg, via the umbilical cord. As this treatment was only partially effective, the mother was also given amiodarone 800 mg/day at week 28, then the dose was reduced to 400 mg/day. However, at the 31st week, the mother showed signs of digoxin intolerance, and it was replaced by sotalol. Fetal blood tests at week 34 showed a high placental transfer of digoxin and sotalol and a low fetal level of amiodarone. The newborn, a girl, was born at the 36th week having a sinus rhythm. She developed signs of hypothyroidism (T4: 4 micrograms/ml; TSH:325 microliters U/ml at 5 days of life). CONCLUSION: The placental transfers of sotalol, digoxin and amiodarone are in the range of values known to be effective. The amiodarone responsible for hypothyroidism was given to the mother because she was intolerant to digoxin. Its use must be limited to arrhythmias that are resistant to other drugs or complicated by hydrops fetalis. When used, amiodarone should not be given for more than 6 weeks, and at the lowest possible dose. PMID- 1288459 TI - [Iconographic rubric. A case with tropical pulmonary eosinophilia]. PMID- 1288460 TI - [A limit of anxiety disorders. Obsessive-compulsive disorders in children and adolescents]. PMID- 1288461 TI - [Development and physiopathology of biliary secretion]. PMID- 1288462 TI - [Fetal cardiology. Evaluation and perspectives]. PMID- 1288463 TI - [Decreased north-west/south-east gradient in geographical distribution in the principal mutation (delta F508) of mucoviscidosis in France]. PMID- 1288464 TI - [Maternal-fetal vitamin D deficiency in Marseille]. PMID- 1288465 TI - [Cow's milk protein intolerance and hypoallergenic milk]. PMID- 1288466 TI - [Acute mitral insufficiency by chordae rupture revealing acute articular rheumatism]. PMID- 1288467 TI - [Alpha-thalassemia in congolese child population in Brazzaville]. PMID- 1288469 TI - [Monotherapy and treatment of fever in children]. PMID- 1288468 TI - [Apnea in an infant after administration of naphazoline]. PMID- 1288470 TI - [Problems posed by the use of row and lyophilized human milk]. PMID- 1288471 TI - Haematological values of rusa deer (Cervus timorensis russa) in New Caledonia. AB - Blood samples were collected from 91 rusa deer (Cervus timorensis russa), immediately after being shot, to define their mean haematological values (red cell count, white cell count, differential leucocyte count, packed cell volume, haemoglobin concentration, mean cell volume, mean cell haemoglobin, and mean cell haemoglobin concentration). Male deer had a significantly higher red cell count and haemoglobin concentration, and a lower mean cell volume and mean cell haemoglobin content, than did female deer. PMID- 1288473 TI - Mesothelioma in horses. AB - Pleural mesothelioma and pericardial mesothelioma with spread to the pleural cavity were diagnosed in 2 horses. Clinical signs included respiratory distress, depression and pleural pain. The affected body cavities contained copious, serous effusions containing very large neoplastic mesothelial cells with densely staining cytoplasm, hyperchromic nuclei and prominent, often multiple, nucleoli. Ultrastructurally, the neoplastic cells appeared as solid aggregates, with profuse microvillous borders and neolumen formation. Cytological examination, together with confirmative ancillary diagnostic tests, including electron microscopy and immunocytochemistry, may be used to obtain an ante-mortem diagnosis of mesothelioma. PMID- 1288472 TI - Serum biochemical values of rusa deer (Cervus timorensis russa) in New Caledonia. AB - Blood samples were collected from 91 rusa deer (Cervus timorensis russa), immediately after being shot. Serum mean biochemical values from shot deer are presented for blood urea nitrogen, creatinine, creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, albumin, calcium, and phosphorus. Mean total protein and albumin increased with age. There was an age-associated increase of gamma globulins. Mean creatine kinase activity and creatinine, albumin and phosphorus concentrations were higher in stags than in hinds. Pregnant hinds had lower mean creatine kinase activity and phosphorus and higher mean alanine aminotransferase and total protein than non-pregnant hinds. Mean calcium concentration increased when deer were agitated before bleeding. PMID- 1288474 TI - Within and between observer agreement on ultrasonic evaluation of bovine ovarian structures. AB - A diagnostic ultrasound unit with a 5 MHz probe was used to examine ovarian structures in vitro from 32 reproductive tracts obtained at slaughter from young cows. Agreement between and within observers, and between observers and dissection results was evaluated using the kappa statistic. Agreement was high (kappa from 0.531 to 0.969) for all evaluations of corpora lutea. The sensitivity, specificity and predictive value of both positive and negative findings for presence of a corpus luteum was > 0.9. Agreement between and within observers was little better than chance for follicles measuring 4 to < 6 mm and for follicles measuring 6 to < 10 mm. However, agreement between observers and dissection results indicated that observers could detect follicles 4 to < 6 mm and 6 to < 10 mm (kappa 0.301 to 0.731 and 0.414 to 0.612, respectively). Kappa values within and between observers and between observers and dissection results for observations of follicles measuring > or = 10 mm were almost all > 0.4 indicating that large follicles can be readily detected using ultrasound. It is suggested that further validation of ultrasound methods is needed to determine whether follicles measuring < 4 mm can be accurately identified, and whether follicles can be accurately identified and monitored over a number of days. The ultrasound unit was useful for detecting the presence of corpora lutea and follicles. However, agreement between and within observers on the presence of follicles measuring < 10 mm was poor. PMID- 1288475 TI - The survival and fecundity of buffalo flies after treatment of cattle with three anthelmintics. AB - Two anthelmintics with known insecticidal action (ivermectin and closantel) and one with no recorded effect on insects (levamisole) were tested to evaluate their effects on buffalo fly (Haematobia irritans exigua). Blood from animals given closantel or levamisole had no significant effect on mortality of buffalo flies in an in-vitro assay. In contrast, blood from animals given ivermectin showed a dose-dependent effect on the mortality of buffalo flies. At 24 h after one injection of the recommended dose of ivermectin, 98% of the flies applied to cattle in an in-vivo assay are killed. Blood from cattle injected with ivermectin killed 95% of flies 8 d after injection and still killed 15% of flies at 18 days after injection. Surviving flies laid almost no eggs and this effect on flies was significant up to 33 d after injection. The results indicate that ivermectin may be useful to control buffalo fly populations in the field. PMID- 1288476 TI - Reduced growth of Lucilia cuprina larvae fed serum from sheep treated with anthelmintics. AB - The effect of three commonly used anthelmintics, levamisole hydrochloride, ivermectin and closantel, on the development of the sheep blowfly, Lucilia cuprina, was determined. Sheep were treated with each anthelmintic using the manufacturers' recommended dose for helminth control. Both ivermectin and closantel significantly (p < 0.05) reduced the growth rate of larvae of L cuprina cultured in vitro on serum from these sheep. Levamisole hydrochloride had no effect. Ivermectin was effective for less than 6 days after treatment, whereas closantel significantly reduced larval growth 21 days after treatment. Dose response experiments showed that lower concentrations of both ivermectin and closantel were not as effective in reducing larval growth. PMID- 1288477 TI - Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1992. AB - Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from February 1991-March 1992 inclusive. The number of reports received/number of animals involved per species was: dogs (23/24); cats (20/30); horses (4/4); cattle (7/10); sheep (3/745); poultry (1/580); pigs (1/8). Of these, 38 (64%) were classified as definite ADRs and 9 (15%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Two reports involved veterinarians inadvertently overdosing animals. Eighteen reports involved apparent hypersensitivity reactions and 6 reports involved probable drug interactions. Four reports involved the use of drugs at appropriate doses but in inappropriate clinical situations, and 3 reports were associated with 'off-label' use. PMID- 1288478 TI - Trace element deficiency in sheep in East Gippsland, Victoria. PMID- 1288479 TI - Biomarkers: signals between health and disease. PMID- 1288480 TI - [Diabetes type II]. PMID- 1288482 TI - [Hypertension]. PMID- 1288481 TI - [Early recognition of hyperlipoproteinemias and intervention]. PMID- 1288484 TI - Predisposition, early recognition, and intervention with overweight. PMID- 1288483 TI - [Early recognition and treatment of diet-dependent diseases--gout]. PMID- 1288485 TI - [Colorectal carcinoma, a diet-dependent disease. Early signs of an increased risk]. PMID- 1288486 TI - Coeliac disease: digestive, immunologic, and nutritional implications. PMID- 1288487 TI - [Osteoporosis: early recognition and prevention]. PMID- 1288488 TI - [Vitamin status and health risks]. PMID- 1288489 TI - Nutrition in medicine: some aspects and perspectives. PMID- 1288490 TI - Salting-out behaviour of the domains of ovomucoid. AB - The solubility of ovomucoid and of four fragments comprising domain I, I+II, and III of the protein in concentrated ammonium sulphate solution were studied at different pHs (25 degrees C) and at various temperatures (pH 7.0), and the salting-out parameters Ks and beta were determined for the five proteins. The aqueous solubilities of ovomucoid and the four fragments were highly dependent on temperature which causes structural alteration due to thermal unfolding of the proteins. The values of KS and beta for domain III and domain II+III at different pHs were similar to those of other globular proteins whereas those of ovomucoid and domain I and domain I+II were atypical. They were explained in terms of the lack of structural stability and the presence of carbohydrate moieties in domains I and II. PMID- 1288491 TI - Beta-glucosidase of a white-rot fungus Trametes gibbosa. AB - Extracellular beta-glucosidase was purified from a white-rot fungus, Trametes gibbosa by 50% ammonium sulphate saturation and Sephadex G-100 column chromatography. It showed maximum activity towards p-nitrophenyl- beta-D- glucopyranoside (pNpG). The pH optimum was 3.5. Temperature optimum was 40 degrees C but shifted to 50 degrees C on preincubation with pNpG. Hg2+, Fe3+ and Cu2+ strongly inhibited the activity. The enzyme was competitively inhibited by glucose with a Ki of 5.2 mM. The apparent molecular mass as determined by gel filtration chromatography was 640 kDa. PMID- 1288492 TI - Characterization of lipoprotein lipase activators from equine plasma. AB - Equine plasma lipoproteins were fractionated into VLDL, LDL-1, LDL-2 and HDL by density gradient ultracentrifugation. From each lipoprotein fraction, five apo C like peptides of approx. M(r) 1400, 10000, 9500, 9000 and 8000 were detected by SDS-polyacrylamide gel electrophoresis. After partial purification by Sephadex G 75, one fraction, showing a strong activation of lipoprotein lipase, was further purified by Mono Q anion exchange column. Two of the apo C like peptides (M(r) 10000 and 8000) activated the bovine milk lipoprotein lipase in vitro; only one (M(r) 9500) inhibited the lipolytic activity. This work confirms that many mammals present two apo C-II components with different molecular weights. PMID- 1288493 TI - Lower susceptibility of low density lipoprotein to in vitro oxidation in diabetic patients. AB - The susceptibility to peroxidative stress of low density lipoprotein (LDL), induced by incubation with CuSO4, has been studied in eleven diabetic patients and eleven control subjects. Our results suggest that oxidized LDL (OX-LDL) of diabetic patients have a significant higher reactivity to 2,4,6-trinitrobenzene sulfonic acid (TNBS) than controls, that indicates a lower susceptibility of LDL to oxidative stress. Furthermore using the fluorescence polarization (Pf) of 1,6 diphenyl-1,3,5-hexatriene (DPH) and its phosphatidylcholine derivative (DPH-PC) we have shown that peroxidation induces a decrease of fluidity in OX-LDL of controls and diabetic patients, both at the lipoprotein surface, where is localized DPH-PC and at the interface between lipoprotein surface and core which is probed by DPH. PMID- 1288494 TI - Isolation and partial characterization of hyaluronan-protein-collagen complex (HA PC) from fetal sheep skin of different gestational ages. AB - Hyaluronic acid (HA) has a positive effect on cell migration, differentiation and wound healing. Earlier work from our laboratory has shown the presence of biologically active proteins associated with HA. The protein associated with HA of fetal sheep skin varies in molecular weight depending on its gestational age. Specifically, the protein profile changes at 125 days of gestation, from a 60 KDa protein to a smaller protein of about 21 KDa. This time period coincides with the time that scarring becomes apparent in fetal sheep skin wounds. In this study, we have quantified changes in the proteins associated with HA with increasing gestational age, obtained amino acid profiles of these proteins with increasing gestational age, and proposed the existence of an HA-associated protein-collagen complex (HA-PC) which may serve as a scaffold for wound healing. Our results indicate that HA-PC content decreases from 42% of the dry weight at 75 days of gestation to 22% at 125 days of gestation. Protein content, in contrast, increases to 40% of the dry weight at 140 days of gestation. At the same time, collagen content increases from < 1% of the dry weight at 75 days to > 10% at 140 days. The increase in collagen content may account for the increase in total protein seen at 140 days. The expression of varying HA-PC's at different gestational ages may influence the kinetics of collagen fibrillogenesis and thus account for the previously noted late gestational change from "scarless" wound healing to "adult-like" wound healing in fetal sheep. PMID- 1288495 TI - The cholinergic agonist carbachol reduces intracellular beta-amyloid precursor protein in PC 12 and C6 cells. AB - Amyloid beta-protein, the major constituent of amyloid plaques in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). Changes in the rates and or pathways of APP synthesis and degradation may be central to the deposition of beta-amyloid. We explored the possibility that APP processing is regulated by activation of endogenous cell-surface neurotransmitter receptors by stimulating C6, PC12 and neuroblastoma cells with the cholinergic agonist carbachol. We measured the intracellular APP in these cell lines by western blotting using three antibodies against different regions of APP. When cells were treated with carbachol for different periods, PC12 and C6 cells responded with a sharp decrease of APP bands. Similar blots probed with an antibody against heat shock protein (HSP), showed no change in the intensity of the immunoreactive HSP 70 band. These results suggest that the decrease in intracellular APP seen after stimulation by carbachol has some specificity and that APP processing may be regulated by stimulation of cholinergic receptors on the surface of cells. PMID- 1288496 TI - Substrate binding properties of L-glycerol-3-phosphate dehydrogenase in isolated liver mitochondria of hyperthyroid rats. AB - In isolated, intact liver mitochondria from hyperthyroid rats, the L-glycerol-3 phosphate binding site(s) of the L-glycerol-3-phosphate dehydrogenase was (were) found to be influenced by the nature of the electron acceptor, as well as by the pH and the presence of calcium ions. With the hydrophobic electron acceptor menadione a single L-glycerol-3-phosphate binding site was detected kinetically at bulk pH values between 6.5 and 9.0. With the hydrophilic phenazine methosulfate, on the other hand, two L-glycerol-3-phosphate binding sites were distinguishable at pH > or = 7.5 and pH > or = 7.0, in the presence and absence of Ca2+, respectively. The kinetic mechanism of the reaction catalyzed by L glycerol-3-phosphate dehydrogenase is ping pong Bi Bi with a hydrophilic electron acceptor, where as with the hydrophobic substance, a sequential Bi Bi mechanism was observed. We suggest that the latter mechanism has physiological relevance. PMID- 1288497 TI - Stimulation of Nb2 mitogenesis by an analogue of human growth hormone (110-127). AB - Two 18-mer peptides were synthesized. Peptide E117 had the same amino acid sequence as that in the region 110-127 of human growth hormone [hGH (110-127)]. In the second peptide (L117), E117 was replaced with leucine. Biological activity of the peptides was assessed in cultured Nb2 lymphoma cells. L117 stimulated cell division and DNA synthesis in a concentration-dependent manner. Maximum stimulation was equivalent to that noted with native hGH although L117 was much less potent (L117; EC50 approximately 1 microM vs. hGH; EC50 approximately 20 pM). No demonstrable activity was found with peptide E117. These results suggest that the amphipathic helical structure of hGH (110-127) is crucial for biological activity. PMID- 1288498 TI - Distribution and antioxidant activity of a palm oil carotene fraction in rats. AB - The aim of this study was to determine the tissue distribution of carotenoids in palm oil and to correlate the accumulation of carotenoids with protection against oxidative stress. We found that: (i) After 2 weeks beta-carotene in the liver increased from 7.3 to 30 ng/g wet tissue; alpha-carotene and lycopene after 10 weeks of feeding were 74 and 49 ng/g wet tissue respectively; (ii) Beta-carotene content in heart and hind limb skeletal muscles increased after 10 weeks to 17 and 6 ng/g wet tissue respectively; (iii) No carotenoids were detected in the brain, adipose and skin during the period of feeding; (iv) After in vitro induction of lipid peroxidation in liver homogenates by an azo-initiator of peroxyl radicals an inverse correlation between tissue carotenoid level and accumulation of lipid peroxidation products was observed; alpha-carotene > lycopene > beta-carotene. PMID- 1288499 TI - Nucleotide sequence of cDNA for porcine heme oxygenase and its expression in Escherichia coli. AB - The nucleotide sequence of a cDNA for porcine heme oxygenase was determined. The open reading frame encoded a polypeptide of 288 amino acid residues with a molecular mass of 33,074 Da. A prokaryotic expression plasmid carrying porcine heme oxygenase cDNA was constructed and transfected into Escherichia coli cells. The full-length heme oxygenase expressed was localized in the bacterial membranes. Two small-sized heme oxygenases with no membrane-bound properties were also detected, suggesting that in E. coli cells a considerable amount of the enzyme expressed was degraded. PMID- 1288500 TI - Myotoxicity and physiological effects of three Trimeresurus flavoviridis phospholipases A2. AB - When basic proteins I and II from Trimeresurus flavoviridis (Habu snake) venom, which are Lys-49-phospholipase A2 (PLA2) with low activity, were injected intramuscularly into mice, myonecrosis was induced accompanied by a rapid increase of plasma creatine kinase level. This increase was about 2 times greater than that raised by highly active T. flavoviridis Asp-49-PLA2 which has been regarded as a myotoxic factor. Calcium-dependent depolarization of frog muscle fibers was observed with basic proteins I and II but not with Asp-49-PLA2. Indirect hemolysis of rat erythrocytes was induced by Asp-49-PLA2 but not by basic proteins I and II. Myotoxicity and depolarization effects appear to be not necessarily related to lipolytic activity of proteins although hemolytic effects is in parallel to lipolytic potency. Light microscopic observations of muscle preparations treated with three PLA2s showed similar histological changes, i.e., myolytic necrosis without hemorrhage and infiltration of polymorphonuclear cells. The structural and functional elements of PLA2s for eliciting myotoxicity are discussed. PMID- 1288502 TI - Immunodetection of tubulin carboxypeptidase activity on nitrocellulose membrane after gel electrophoresis and blotting. AB - It was found that the detyrosination of tyrosinated tubulin by tubulin carboxypeptidase can occur when both the enzyme and the substrate are adsorbed on nitrocellulose. This, and the use of a specific antibody that recognizes detyrosinated tubulin allowed us to localize tubulin carboxypeptidase on a nitrocellulose membrane after agarose gel electrophoresis and blotting. The method was also extended to detect pancreatic carboxypeptidase A. PMID- 1288501 TI - In vitro transfer of N-acetylglucosamine to endogenous glycoprotein acceptors catalyzed by the nucleus and the cytoplasmic membranes prepared from L1210 cells. AB - The non-nuclear membranes and the nuclei prepared from L1210 cells catalyze the in vitro transfer of N-acetyl(14C)glucosamine from UDP-N-acetyl(14C)glucosamine to endogenous glycoprotein acceptors. Adequate analysis of these acceptors have demonstrated that the nucleus has its own N-acetylglucosaminyltransferase system that leads to the formation of N-N'-diacetylchitobiosylated proteins. PMID- 1288503 TI - Interaction between phenylalanine and antisense nucleosides and the effect of pH and salts on the strength of interaction. AB - The interaction of 12 antisense nucleosides with phenylalanine (Phe), and the effect of pH and salts on the strength of interaction was studied by charge transfer reversed-phase thin-layer chromatography. Phe significantly decreased the lipophilicity of nucleosides. This effect may be due to the interaction between the more hydrophilic Phe and the more lipophilic nucleosides, resulting in charge-transfer complexes of moderate lipophilicity. The relative strength of interaction was the weakest in acidic and the strongest in alkaline environment. This finding indicates the partially or entirely hydrophilic character of the interaction. Salts influenced to a lesser extent the interaction, their effect depended both on the concentration and on the type of cation. The relatively low impact of salts on the strength of interaction suggests that other than hydrophilic forces are involved in the Phe - antisense nucleoside interaction. PMID- 1288504 TI - Identification of human salivary protease activity toward mucin: differences with caries. AB - A protease activity directed toward high molecular weight salivary mucus glycoprotein was identified in the secretion of human submandibular salivary gland. The protease exhibited maximum activity at pH 7.0-7.4, and following ammonium sulfate fractionation yielded an active enzyme at 60% saturation which on SDS-PAGE gave 48 and 53kDa protein bands. The enzyme exhibited serine-protease properties by showing susceptibility to phenyl methyl sulfonyl fluoride, alpha 1 antitrypsin, and egg white and soybean inhibitors. The protease activity in submandibular saliva of caries-resistant subjects was found to be 3.8-fold greater than that in saliva of caries-susceptible individuals, thus suggesting that the enzyme expression may be linked to the resistance to caries. PMID- 1288505 TI - Hammett rho sigma correlation for the inhibition by indoles of coniferyl alcohol oxidation catalyzed by cell wall peroxidases. AB - The inhibitory effect of indole-3-acetic acid, and of its peroxidase-mediated degradation products of an indole nature, on the oxidation rate of coniferyl alcohol catalyzed by cell wall peroxidases has been studied. The results show that the inhibitory effect of indole-3-acetic acid and indole-3-carbinol may be explained, in part, by their properties as peroxidase substrates. However, I50 values for a series of indole compounds not regarded as peroxidase substrates show a good correlation with the electron-donating or electron-withdrawing nature of the 3-substituents, as judged by the linearity of the Hammett rho sigma plot. These results suggest that although the properties of indole compounds as peroxidase substrates may be responsible, in part, for their inhibitory effects on the peroxidase-mediated oxidation of coniferyl alcohol, the inhibitory effect appears to be mainly determined by the acidity of the imino group of the indole nucleus. PMID- 1288506 TI - Toxicity studies of the non-sulfhydryl angiotensin converting enzyme inhibitor N [8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline in rats. AB - The acute and subacute toxicities of N-[8-amino-1(S)-carboxyoctyl]-L- alanyl-L proline (AB-47, CAS 120008-53-9), which is a non-sulfhydryl angiotensin converting enzyme inhibitor, were studied in male and female Fischer 344 rats. In the acute study, male and female rats were orally given 5000 mg/kg of AB-47. No rats were dead during the observation period (14 days) after the administration. The LD50 values of AB-47 were more than 5000 mg/kg in both male and female rats. Although only diarrhoea as toxic sign was observed 2 to 7 h after the administration, this sign disappeared within 24 h after the administration. Necropsy at the termination of observations revealed no macroscopic lesions in any rats. In the subacute study, male and female Fischer 344 rats were orally given 40, 200 or 1000 mg/kg/d of AB-47 for 4 weeks. Neither toxic signs nor death due to drug effects were observed at any dosage levels of AB-47. Furthermore, AB 47 did not influence body weight, food consumption, food efficiency, urinalytical and hematological parameters in both male and female rats. The minor changes of serum parameters, which consisted of very slight increases in serum potassium and decreases in serum albumin/globulin ratio, occurred in male rats given 200 and 1000 mg/kg/d of AB-47. Serum urea nitrogen values were elevated in both male and female rats given 1000 mg/kg/d of AB-47. Slight decreases of heart weight and heart weight/body weight ratios were observed at all dosage levels of AB 47.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288507 TI - Effect of slow release nifedipine tablets in patients with essential hypertension. AB - The antihypertensive effect of slow release nifedipine (CAS 21829-25-4) tablets (20 mg, Adalat) administered once or twice daily was studied in patients with essential hypertension of WHO stage I or II. Ambulatory blood pressure was monitored by a finger volume oscillometric device every 5 min for 24 h before and during the treatment with nifedipine. Whether administered once or twice daily, nifedipine tablets dit not change the pattern of circadian blood pressure variation; i.e. diurnal rise and nocturnal fall. Twice daily administration induced a significant downward shift in the blood pressure pattern. In other words, further hypotensive effect was observed during the night when the blood pressure was already low. On the other hand, administration once daily in the morning lowered daytime blood pressure without affecting blood pressure during the night. The duration of action of nifedipine tablets administered once daily was 12 h or more. In the acute experiment using 20 mg tablets of nifedipine, plasma concentration of nifedipine was well correlated with the percentage change in mean blood pressure. The minimal effective plasma concentration of nifedipine was estimated to be 13.4 ng/ml. However, in chronic treatment, nifedipine lowered blood pressure at the plasma concentration of 10 ng/ml. The results indicate that nifedipine tablets administered once daily provide an effective antihypertensive regimen for controlling daytime hypertension with minimal antihypertensive effect during the night. PMID- 1288508 TI - Structure/histotoxicity relationship of parenteral iron preparations. AB - Commercial iron preparations with different chemical structures and stabilities which are indicated for parenteral application were analyzed. After intravenous application in mice, toxic effects were screened by histological examination of liver, kidney, adrenal, lung and spleen. The various iron complexes were classified into four groups according to their physicochemical properties (molecular mass, kinetic and thermodynamic stability). It was found that the toxic effects can be forecasted by the chemical properties. The results clearly show that not all iron preparations tested can be recommended for intravenous application. After injection, the ideal iron preparation is deposited in the reticulo-endothelial system, and not in the parenchyma of the liver, nor mainly in the periportal area. Furthermore, its renal elimination rate should be below 1% of the dose, and there should be practically no iron detectable in the tubuli. The molecular mass of an optimal product is between 30,000 and 100,000 Daltons, and the preparation does not contain any slowly degradable biopolymers, so that the incidence of allergic side effects is reduced to a minimum. Iron preparations consisting only of weak iron complexes, which liberate iron ions stochastically, should not be used for intravenous application. PMID- 1288509 TI - Studies on some 10-[2-(N,N-disubstituted thiocarbamoylthio)acetyl]phenothiazine derivatives. AB - Nineteen 10-[2-(N,N-disubstituted thiocarbamoylthio) acetyl]phenothiazine derivatives have been synthesized by the reaction of 10-chloroacetylphenothiazine with potassium salt of N,N-disubstituted dithiocarbamic acid derivatives. The structures of the compounds have been elucidated by UV, IR, 1H-NMR spectra and microanalysis. The anticholinergic activity of the compounds was determined by assessing the inhibition of acetylcholine using atropine sulfate as a control. Results are discussed in relation to the activity and structure of the synthesized compounds. PMID- 1288510 TI - Ultrasound studies of the effect of trospium chloride on gall-bladder kinetics. AB - In a randomized double-blind study the effects of increasing doses of trospium chloride (Spasmo-lyt, CAS 10405-02-4), 0.2, 0.5, 1.0, and 1.5 mg i.v., on gall bladder contractility were compared among themselves and against placebo and n butylscopolamine bromide (20 mg i.v.) by an intraindividual 5-fold crossover technique. Gall-bladder volumes after drug-induced contraction (fat stimulus with sodium iopodate) were measured by ultrasound scanning conducted by a single examiner. Serial measurements, carried out in 6 female subjects without any evidence of gall-bladder disease, demonstrated a dose-dependent trend of inhibition of gall-bladder motility produced by trospium chloride. In the maximal doses employed (1.0 and 1.5 mg i.v.) trospium chloride effected almost total inhibition of motility. The response to n-butylscopolamine bromide tested in a nonblind comparison, showed a dose-effect ratio of roughly 40:1 between trospium chloride and n-butylscopolamine bromide given intravenously. This work confirms that ultrasound measurement of gall-bladder volume is a suitable pharmacodynamic model for testing the dose-effect relationships of antispasmodic agents. PMID- 1288511 TI - Effects of propiverine hydrochloride on the spontaneous contractions of isolated guinea-pig urinary bladder strip and rhythmic urinary bladder contractions of anesthetized dog. AB - The effects of propiverine hydrochloride (P-4, CAS 60569-19-9), a new drug to treat pollakiuria, was investigated on the spontaneous contractions of isolated guinea-pig urinary bladder strip and rhythmic urinary bladder contractions of anesthetized dog. At 10(-6)-10(-5) mol/l P-4 raised the base line of an isolated guinea-pig urinary bladder strip and accelerated its spontaneous contraction. At 10(-4) mol/l P-4 raised, and then lowered the baseline, and accelerated then suppressed its spontaneous contractions. Papaverine at 10(-6)-10(-4) mol/l also showed a similar action as P-4 in the isolated guinea-pig urinary bladder strip. Flavoxate at 10(-6)-10(-4) mol/l raised its base line and accelerated its spontaneous contractions. Those of P-4 at 10(-5) mol/l were not inhibited by tetrodotoxin 10(-6) mol/l). At doses of 50 mg/kg or more, intraduodenal administration of P-4 suppressed the frequency of rhythmic urinary bladder contractions of anesthetized dog in a dose-dependent manner. These results indicate that P-4 shows mainly an accelerating action on the endogenous spontaneous contractions of urinary bladder, but on exogenous contractions induced by the Balloon's method it shows an suppressing action and regulates the functions of the urinary bladder, so P-4 might become a useful drug for the clinical treatment of micturitional dysfunction, for example, pollakiuria. PMID- 1288512 TI - Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate. AB - The efficacy and tolerance of a garlic preparation (Sapec, Kwai) was investigated in a randomized double-blind study vs. bezafibrate. This multi-centre study was conducted in 5 general medical practices and involved 98 patients with primary hyperlipoproteinaemia. The daily doses of the active substances were 900 mg of garlic powder (standardized as to 1.3% alliin) and 600 mg of bezafibrate, respectively. The pre-phase with placebo lasted 6 weeks, the treatment period covered 12 weeks. All patients were advised to observe a low-fat "step-1 diet" for the duration of the study. The 98 case report forms allowed the statistical evaluation of total cholesterol, HDL cholesterol and triglyceride levels for 94 patients, and of LDL cholesterol values for 92 patients. In the course of the treatment both study medications caused a statistically highly significant reduction in total cholesterol, in LDL cholesterol and triglycerides, and an increase in HDL cholesterol. However, there was no significant difference in the efficacies of both medication groups. Side effects were mentioned by 5 patients each in both treatment groups, none of which led to the withdrawal of the patients. Concerning the garlic preparation, there was no correlation between the perception of garlic odour and the influence on the cholesterol level. PMID- 1288513 TI - [Plasma- and tissue concentrations following intramuscular administration of etofenamat. Pharmacokinetics of etofenamat and flufenamic acid in plasma, synovium, and tissues of patients with chronic polyarthritis after administration of an oily solution of etofenamat]. AB - Studies on Plasma and Tissue Concentrations of Etofenamate following Intramuscular Application/Pharmacokinetics of etofenamate and flutenamic acid in plasma, synovia and tissues of patients with chronic polyarthritis after application of oily etofenamat solution Pharmacokinetics of etofenamate (ETO, CAS 30544-47-9; Rheumon i.m.) and flufenamic acid (FLU, CAS 530-78-9) were investigated in plasma, synovial fluid, and tissues after single intramuscular application of etofenamate to patients with rheumatoid arthritis. 62 patients with indicated operative procedure in the knee-joint received a single dose of etofenamate dissolved in oil before operation. At definite times between 1.5 and 48 h post injectionem samples from 6 patients of each time group were collected. Samples of plasma, synovial fluid, synovial membrane, muscle, bone, hyaline cartilage, and fat tissue and in some cases meniscus cartilage were taken. Concentrations of ETO and its active metabolite, FLU, were determined by HPTLC. In all tissues investigated, concentration/time courses of ETO and FLU were observed. ETO and FLU were measured first in all matrices 1.5 h at the latest 3 h post injectionem. Pharmacokinetics in tissues follows that in plasma. Rate limiting step is the liberation of drug from the oil depot. For a long period pharmacokinetics of ETO and FLU is mainly determined by the constant liberation from the oil depot (zero order kinetics of liberation). Zero order kinetics is deduced from the linear ascent of the cumulated AUC (in percent) vs. time plot. It is directly related to the liberation of drug from the galenical formulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288514 TI - [Protective effect of ranitidine in the stomach and duodenum against piroxicam. An endoscopy controlled double-blind study]. AB - Protective Effects of Ranitidine in Stomach and Duodenum against Piroxicam / An endoscopically controlled double-blind study In a randomized parallel double blind study the gastroduodenal effects of 20 mg piroxicam (CAS 36322-90-4) daily in the presence and absence of 300 mg ranitidine nocte was evaluated in 28 healthy volunteers undergoing upper gastrointestinal endoscopy. Drugs were taken over a period of 14 days. Endoscopic controls were performed at entry, and repeated after 7 and 14 days of treatment. A damaging score according to Lanza et al. was used. At entry, both groups displayed comparable mucosal damages in the stomach (0.9 +/- 0.1) and in the duodenum (0.4 +/- 0.2). After 14 days the mean lesion score increased in the piroxicam/placebo group to 6.3 +/- 1.6 in the stomach and to 4.0 +/- 1.4 in the duodenum. The corresponding values in the piroxicam/ranitidine group were 3.4 +/- 1.0 (stomach) and 0.4 +/- 0.2 (duodenum). This protection afforded by ranitidine was significant when compared with placebo (p < 0.05). Our data suggest that 300 mg ranitidine at night markedly protect the stomach and the duodenum against piroxicam. PMID- 1288515 TI - N-substituted 2-isocyanoarylacetamides with antimicrobial activity. AB - In this study, N-substituted 2-formylaminoarylacetamides (3) were obtained by the Ugi four-component reaction between isocyanides (1), aldehydes (2), and ammonium formate. The reaction products (3) were dehydrated with POCl3/NEt3 to give the title compounds (4). The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analysis. Tests of antimicrobial activity showed that compounds 4 were ineffective against E. coli and fairly active against K. pneumoniae and S. aureus. A better activity was shown against B. subtilis, but all the tested compounds showed a very good inhibitory effect against C. albicans. PMID- 1288516 TI - Metabolic N-hydroxylation of diminazene in vitro. AB - The two N-hydroxylated derivatives (amide oximes) and the corresponding amides of the trypanocidal diamidine diminazene (Berenil, CAS 536-71-0) have been synthesized. These reference compounds made it possible to investigate the in vitro metabolism of the amidine functionalities of diminazene. Diminazene metabolites were detected for the first time, in the form of the corresponding mono- and di(amide oxime), after incubation with 12000 g supernatants from rabbit liver homogenates and careful workup (freeze drying). The identification was based on the behavior in thin-layer chromatography and on comparison of the mass spectral data for the metabolites with those for synthetic material. The N hydroxylation of diminazene showed the properties typical of a reaction catalyzed by a microsomal monoxygenase. Diminazene amides did not occur as metabolites. The di(amide oxime) of diminazene was tested for its trypanocidal and leishmanicidal activity on various laboratory strains of trypanosomes in mice and on Leishmania donovani in hamsters. The studies showed that the di(amide oxime) has a trypanocidal effect on various strains of trypanosomes (T. brucei, T. vivax, T. congolense and T. evansi), but this is distinctly weaker than that of diminazene. A diminazene-resistant strain of T. rhodesiense is also unaffected by the di(amide oxime). The di(amide oxime) also has a leishmanicidal effect, but this again is distinctly less than that of diminazene. PMID- 1288518 TI - Is Dhat culture bound? PMID- 1288517 TI - Isolation and renaturation of bio-active proteins expressed in Escherichia coli as inclusion bodies. AB - Over-expression of recombinant proteins in Escherichia coli often results in the formation of insoluble and inactive material as inclusion bodies. Within the last years specific methods and strategies have been developed to produce bio-active proteins from these inclusion bodies. These methods include (i) isolation and purification of inclusion bodies, (ii) solubilization and reduction of the insoluble material, and (iii) renaturation of the proteins including formation of native disulphide bonds. Inclusion bodies are isolated from E. coli cells after desintegration of cells by mechanic forces. Due to their stability, inclusion bodies may be purified by washing with detergent solutions or low concentrations of denaturant. High concentrations of urea and guanidine hydrochloride are used in combination with reducing reagents such as 2-mercaptoethanol or dithiothreitol to reduce and solubilize proteins from inclusion bodies. After purification of solubilized materials, proteins are renatured and native disulphide bonds are formed by either air oxidation or glutathione reoxidation starting from reduced material, or by disulphide interchange starting from mixed disulphides containing peptides. Final yield of renatured proteins is raised by low concentrations of proteins and by adding low concentrations of denaturant during renaturation. PMID- 1288519 TI - Comparison of plasma bismuth levels after oral dosing with basic bismuth carbonate or tripotassium dicitrato bismuthate. AB - In 20 healthy subjects plasma bismuth concentration was measured after single oral doses of basic bismuth carbonate or tripotassium dicitrato bismuthate. The drugs were administered in the fasted state or immediately after ingestion of a standard breakfast. After basic bismuth carbonate, plasma bismuth rose to concentrations between 0.7 and 2.6 micrograms/L in the fasted state, while after the meal the maximal level was only 1.3 micrograms/L. In contrast to these very low levels after basic bismuth carbonate, the administration of tripotassium dicitrato bismuthate was paralleled by an increase of plasma bismuth to concentrations between 15 and 232 micrograms/L with a mean peak value of 64 +/- 15.3 (S.E.M.) micrograms/L in the fasted state. Postprandial ingestion of tripotassium dicitrato bismuthate attenuated the peak concentrations to 10.9 +/- 6.3 micrograms/L. One subject, however, had a value of 120 micrograms/L. This study demonstrates that basic bismuth carbonate leads to very low plasma bismuth concentrations, which are far below the critical range that might eventually be associated with bismuth neurotoxicity. Therefore this compound can be considered potentially useful for bismuth therapy of gastrointestinal disorders. PMID- 1288520 TI - Safety of 5-HT reuptake inhibitors. PMID- 1288521 TI - Suicide prevention. PMID- 1288522 TI - Are non-Western beliefs false? PMID- 1288523 TI - Chondrodermatitis nodularis chronica helicis. PMID- 1288524 TI - Desertomycin D, a new desertomycin related antibiotic. PMID- 1288525 TI - Acyclovir: a decade later. PMID- 1288526 TI - Fellowship programs in critical care medicine: 1992/1993. The Society of Critical Care Medicine. PMID- 1288527 TI - HIV infection and certification of death. PMID- 1288528 TI - [Nocturnal enuresis--the wet child. Interview by Grethe Kjaergaard]. PMID- 1288529 TI - The familial occurrence of Parkinson's disease. Lack of evidence for maternal inheritance. AB - A questionnaire concerning the occurrence of Parkinson's disease in parents was administered for 252 patients with Parkinson's disease. Eleven fathers and five mothers of patients were reported to also have had this disease. These data fail to provide support for the hypothesis that Parkinson's disease is the result of maternal inheritance of an abnormal mitochondrial gene. This conclusion is further supported by a review of similar studies in the literature and an additional unpublished study, which revealed that of 922 patients with this disease, 37 fathers and 19 mothers were reportedly affected. PMID- 1288530 TI - A lipophilic protein inhibitor of neutral cholesteryl ester hydrolase: mode of action. PMID- 1288531 TI - OSHA's final bloodborne pathogens standard. Part I. AB - The Bloodborne Pathogens Standard is the first standard promulgated by OSHA that addresses a biological hazard in the workplace. This Standard applies to all workers with occupational exposure to blood or other potentially infectious materials. To achieve compliance, the employer must determine and document exposure. Also, a written exposure control plan must be available that stipulates the use of appropriate methods of compliance such as engineering controls, work practice controls, and the use of personal protective equipment. PMID- 1288532 TI - Hepatitis B vaccine: acceptance among occupational health nurses practicing in hospital employee health settings. AB - Seventy-seven percent of the hospital employee nurses in this study had accepted hepatitis B vaccine, a higher rate than that reported in the literature for other health care workers. The study found a significant relationship between increased perceived susceptibility to HBV and hepatitis B vaccine acceptance. The unvaccinated nurses did not perceive the employee health setting as risky, yet their clientele (health care workers) are five to 10 times more likely than the general population to be hepatitis B carriers. The younger and less experienced nurses were significantly more likely to have been vaccinated. The hepatitis B vaccine should be offered early in the career of employed health care workers, made accessible at the worksite, and offered to student health care workers. Hepatitis B vaccine education and counseling should focus on increasing perceived susceptibility to HBV for all health care workers and stress vaccine safety and effectiveness. PMID- 1288533 TI - Nurse practitioner sutured wounds: a quality assurance review. AB - This study found a low infection rate (3.1%) in occupationally related lacerations sutured by an on site nurse practitioner in a meat-packing plant where a high infection rate might be expected. This is compared to an overall infection rate of 1% to 30% of all sutured wounds cited in other studies. This review suggests that worksite availability of a nurse practitioner with expertise in suturing and aseptic technique is correlated to a low infection rate. Findings suggest that prophylactic antibiotics do not preclude good wound care, but may still be merited in wounds at high risk of subsequent infection. Infected wounds may cost anywhere from $2,000 to $150,000 per case depending on severity, in addition to other hidden costs. Clearly a decrease in the morbidity of wound care is significant in terms of decreased cost. PMID- 1288535 TI - Private industry and public health join forces: an occupational health program for workers at a construction site in rural Alabama. PMID- 1288534 TI - Cardiovascular risk factors in textile workers: prevalence and intervention. AB - This study included 1,390 textile workers from a southern state who received a screening for risk factors for heart disease. Occupational health nurses then provided an education/counseling intervention and one or more American Heart Association pamphlets using the results of the screening. Over half of the workers had at least one modifiable risk factor for heart disease. The most common modifiable risk factor was smoking. Most of the participants (60.8%) had a cholesterol level less than 200 mg/dL, but 27.4% were in the borderline high range of 200-239 mg/dL, and 11.8% had a cholesterol of 240 mg/dL or higher. Almost 26% of the participants had a blood pressure of 140/90 or higher. Findings on a subset of 544 workers re-screened at 6 months were: workers with hypertension were able to lower their blood pressure significantly; cholesterol levels increased slightly in all participants except white males; and although some smokers stopped smoking, others began smoking, so the total number of smokers at the second test was actually slightly higher than at the first screening. PMID- 1288536 TI - Negotiation without confrontation. PMID- 1288537 TI - Linking practice & research. PMID- 1288538 TI - [Fluorocarbon emulsions as injectable oxygen carriers. Recent progress and perspectives]. AB - Fluorocarbon emulsions are presently being developed to serve as injectable oxygen carriers (so-called "blood substitutes"). In this approach oxygen is simply dissolved in the liquid carrier and the amount of gas dissolved is proportional to its partial pressure. Increasing the O2-delivering capacity is therefore achieved more easily by increasing the oxygen content of the air breathed by the patient than by increasing the dose of fluorocarbon administered. The absence of a chemical bond between the gas and its carriers allows over 90% of the transported oxygen to be delivered. The fluorocarbon droplets act as oxygen carriers , and also appear to facilitate its diffusion. Chemically and biologically highly inert, fluorocarbons are excreted by exhalation without being metabolized. The first generation of emulsions, exemplified by Fluosol has only limited efficacy due to its low fluorocarbon content, low intravascular persistence and insufficient stability. It has to be stored and distributed frozen, then reconstituted prior to use. Fluosol has nevertheless been licensed by the Food and Drug Administration for use during high risk PTCA. The second generation of injectable fluorocarbon emulsions, exemplified by Oxygent is 4-5 times more concentrated and consequently more efficacious than Fluosol. Considerably more stable, this emulsion can be stored for over one year at 5-8 degrees C and is ready for use. The fluorocarbon used has a significantly shorter organ-retention time. The applications of the present emulsions are still limited by their short intravascular persistence, and are those for which prolonged efficacy is not required, which includes perioperative hemodilution, ischemia, cardioplegia, reperfusion, sensitization of tumors to radio- and chemotherapy, organ preservation and diagnosis. The efficacy of the new emulsions has been established in various animal models. The mild side-effects observed in Phase I clinical trials appear to result from a transient activation of the monocyte/macrophage system and to be suppressed prophylactically by cyclooxygenase inhibitors or corticosteroids. Research is presently oriented towards controlling intravascular persistence better, increasing emulsion stability further, minimizing side-effects and optimizing emulsion characteristics for specific indications. PMID- 1288539 TI - [Expression of recombinant human hemoglobin]. AB - The well recognized prevalence of infectious agents in products derived from human whole blood and the increasing number of transfusion-transmitted diseases has made urgent the search for a safe alternative to conventional blood transfusion. Sources of hemoglobin (Hb) different from outdated human bank blood are under active scrutiny in several laboratories. Different approaches have been proposed to produce recombinant human Hb in bacteria (E. coli), yeast (S. cerevisiae) and transgenic mammals. These efforts have lead to the synthesis of recombinant human Hb with functional properties similar to those of native human Hb A. Site directed mutagenesis enables one to modify the structure of the recombinant globin chains with the view of lowering the oxygen affinity and increasing the stability of the tetramers. Progress is still necessary to ensure scaling-up and safe purification procedures, and to prolong shelf life of these solutions. PMID- 1288540 TI - [Molecular engineering of hemoglobin for transfusion]. AB - The search for a safe alternative to conventional blood transfusion has been directed towards either the use of synthetic perfluorochemicals or the biochemical manipulation of highly purified stroma-free Hb solutions prepared from outdated bank blood. However when using human blood, one does not eliminate the risks of viral infections. A novel source of Hb appeared with recent biotechnology techniques enabling one to synthesize recombinant Hb from microorganisms (E coli or S. cerevisiae) whose genome has been modified to contain globin genes. Normal human Hb A in solution, i.e. outside the red cells, is not suited for direct usage as a blood substitute because i) its high oxygen affinity, due to the absence of 2,3 DPG in the plasma, precludes sufficient O2 unloading to the tissues; ii) at low concentration, relative to that in the red cells, tetrameric Hb dissociates into dimers which escape the circulatory system by renal filtration or rapidly oxidize to the non functional metHb form. Expression of alpha- and beta-globins in Escherichia coli and in Saccharomyces cerevisiae enables one to introduce appropriate mutation(s) in the globin genes resulting in the expression of a synthetic Hb with low oxygen affinity, resembling that of normal whole blood; functional Hb has also been produced in a soluble form either in E. coli or in yeast. The coexpression of beta globin chains and alpha globin subunits linked by a peptide bond results in the direct synthesis of stabilized and fully functional Hb tetramers. Lastly, dilute haemoglobin solutions are prone to autooxidize and the rate of oxidation appears to be inversely proportional with the oxygen affinity of the heme groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288541 TI - [Regulation of drugs derived from human blood and plasma in the European Community]. PMID- 1288542 TI - [Prion encephalopathies]. AB - Spongiform encephalopathies, also called prion encephalopathies, are characterized, in human as well as in animals, by (1) their clinical picture which indicates strict localisation in central nervous system, (2) their histological aspect: spongiform degeneration and neuronal loss, and (3) their transmissibility in the same animal species but also from man to animal. The nature of the pathogenic agent is still debated. This agent could be one isoform of the prion protein which, probably because of a modification of its tertiary structure, is partially resistant to proteolytic enzymes. Recent description of a bovine spongiform encephalopathy caused by meat flour absorption has raised again the question of the transmissibility of these animal diseases to human. PMID- 1288543 TI - Epidemiology of allergic diseases. AB - At present there is international interest in MA. Different factors are responsible: the severity and prevalent frequency of these diseases; the health cost that they create: more adequate diagnosis and treatment. Understanding of the epidemiology, pathological mechanisms, favouring factors, the start and development of the disease, is essential to establish a diagnosis and appropriate treatment. Several factors trigger MA, with hereditary disposition and allergen exposure the most significant. Without these two associated factors the disease does not appear. However, there are other factors that play an important part in the prevalence of the allergic state and its development. Some are concerned with the individual (age, sex, race), others with the environment (pollution, socio economic, environment, infections...). The author has devoted this article to analysis of these individual factors. PMID- 1288544 TI - IgE modification of the specific antidermatophagoides during the first year of specific immunotherapy (SIT). AB - Six subjects (4 female, 2 male), aged from 16 to 25 years, presented with allergic rhinitis to Dermatophagoides mites and received SIT by the sub-cutaneous route with delayed-release alpha fraction Bayropharm at the standard doses. Diagnosis was based on clinical history, skin tests and measurement of specific IgE at 0, 3, 9, and 12 months, by the fluoro-enzymatic technique (FAST). For comparison, in a reference group (n = 20) the IgE varied between 0.32 and 0.11 IU/ml for D1 and 0.31 to 0.09 IU/ml for D2. The eight patients had specific IgE titres of D1 = 0.96, D2 = 0.99. For these authors, the FAST technique used for the measurement of specific IgE, although less sensitive than the RIA technique of RAST, gives a good evaluation of SIT. PMID- 1288545 TI - Allergic contact dermatitis in Trieste from 1987 to 1991. AB - Between 1987 and 1991, the authors made patch-tests on 1,427 patients, 389 male and 1,038 female, of mean age 36 years (6-70 years) and mostly suffering from eczema. The standard tests of Italian Group for Research into Contact Dermatitis and the Environment (GIRDCA) were used, following the best data of recent years. Nickel sulphate, thiomersal, "Fragrance mix", cobalt sulphate and potassium bichromate were the allergens varied with age: nickel and thiomersal were most frequently positive between 20 and 30 years. In contrast, the highest frequency of positivity to fragrance mix was seen between 40 and 60 years. Positivity to a simple allergen had a tendancy to reduce with age. PMID- 1288546 TI - Psoriatic arthritis treated with cyclosporin A. AB - Cyclosporin A (CyA) is a very effective immunosuppressor for inhibition of the humoral immune response and especially for cell mediation and was originally indicated for transplantation of organs and autoimmune diseases. More recently, CyA has been used successfully for severe psoriasis. In this study, the authors describe the results obtained from 8 patients who presented with a psoriatic arthropathy, treated with small doses of CyA (3-5 mg/kg/day). There were reactions in five of them, in two patients the Ritchie index decreased moderately and in one patient the arthritic psoriasis was significantly improved. PMID- 1288547 TI - A baby-friendly environment: more than a dream? PMID- 1288548 TI - Pain: normal or a signal that something is wrong? PMID- 1288549 TI - Use of a shoe to discuss latch-on. PMID- 1288551 TI - Tea bags and sore nipples. PMID- 1288550 TI - Action without the boycott. PMID- 1288552 TI - Baby-friendly designations: details, please. PMID- 1288553 TI - Proposed US certification eligibility requirements. PMID- 1288554 TI - Breastfeeding resource directory: a great idea! PMID- 1288555 TI - Perspectives of common breastfeeding situations: a known group comparison. AB - Infant feeding choice is influenced by social and cultural factors, as reflected in sociodemographic correlates of breastfeeding, which show consistently low breastfeeding rates among women from low-income populations. This study examines attitudes and beliefs that are thought to affect feeding choice and breastfeeding behavior among diverse social and cultural groups. A breastfeeding behavior questionnaire asking women to respond to a variety of breastfeeding situations presented as narratives was administered to members of a La Leche League group and to a group of WIC participants. Results support the idea that different social groups of women display divergent attitudes toward and perceptions of breastfeeding. Although small sample size prohibits generalization of results, the findings reinforce the necessity of designing breastfeeding education programs within specific cultural contexts. PMID- 1288556 TI - Breastfeeding among women in the Alabama WIC Program. AB - Women who participated in the Alabama WIC Program during 1986-88 and ceased breastfeeding during the months of May to August during those years breastfed an average 5.6 months. Slightly fewer than 15 percent of the women who breastfed continued for 12 months or longer; 45 percent continued for six months; 59 percent did so for 4 months; and 21 percent breastfed for one month or less. Breastfeeding duration was related positively and independently to increased maternal age and parity. Younger women were more likely than older women to stop breastfeeding due to perceived insufficient milk, in order to return to work or school, or to use oral contraceptives. Women who ceased breastfeeding at or after one year postpartum tended to be older. PMID- 1288557 TI - Breastfeeding and migraine headaches. AB - Migraine headaches affect 19 percent of adult women. A small group of these migraine sufferers also are breastfeeding mothers. Although a correlation has not been documented in the literature, some women have noted that the onset, frequency, or pattern of their migraine headaches changes during lactation. Lactation consultants can provide education and support to breastfeeding women suffering from migraine. They also are in an excellent position to add case studies to the scientific database about this phenomenon. PMID- 1288558 TI - The Florida breastfeeding promotion project: a coalition effort to improve hospital practices and policies. AB - The Florida Healthy Mothers, Healthy Babies-Coalition initiated a breastfeeding promotion project. The Coalition focused on hospital policies because of their impact on breastfeeding success and because of the potential for working with other state efforts directed at pregnant women or new mothers. The Florida Healthy Mothers, Healthy Babies Coalition developed a three-part program. It consists of model hospital policies concerning breastfeeding, a lecture series which educates hospital nursing staff on the implementation of these model policies and a workshop through which trainers are prepared to present the educational program. Nurses' Association of the American College of Obstetrics and Gynecology (NAACOG), Special Supplemental Food Program for Women, Infants, and Children (WIC), and Florida Lactation Consultant Association (FLCA) all contributed to this project. PMID- 1288559 TI - Nursing strike: misunderstood feelings. AB - The nursing strike often ends almost as suddenly as it began, and the mother and baby resume nursing with the same pattern as previously, but with a new understanding of their relationship and appreciation of each other's feelings. The best aspect of this technique of "loving" the strike away is that everyone feels good about the situation at its resolution. PMID- 1288561 TI - North American milk banks. PMID- 1288560 TI - Antiinfectives in breastmilk. Part II: Sulfonamides, tetracyclines, macrolides, aminoglycosides and antimalarials. PMID- 1288562 TI - The People's Home Medical Book. 1912. PMID- 1288563 TI - Proposed changes in United States eligibility requirements for board certification. PMID- 1288564 TI - [Is anything happening? Positive action for women in health care]. PMID- 1288565 TI - [Environment and health care (4). Something Florence once started...]. PMID- 1288566 TI - [The consequences of the system modification. A report of Manifestation Day of October 22]. PMID- 1288568 TI - [When are we ready? On the way toward an unequivocal nursing concept framework]. PMID- 1288567 TI - [The Eye Hospital Rotterdam. Waiting in the fog]. PMID- 1288569 TI - [The NHS (Dutch Heart Foundation), or: the fight against public enemy number one. Nursing Advisory Council--reorganized model]. PMID- 1288571 TI - Dental accounts receivable management. An overview. PMID- 1288573 TI - The Benton E. Crawford radiograph of the month. Metastatic carcinoma. PMID- 1288572 TI - ADA/AAP Launch National Screening Program for Early Periodontal Disease Detection. PMID- 1288570 TI - [Care of elderly patients with dementia living at home. A stock-taking case study]. PMID- 1288575 TI - Benton E. Crawford radiograph of the month. Dentigerous cyst. PMID- 1288574 TI - Nocturnal bruxism and sleep stages. PMID- 1288576 TI - The new-generation subperiosteal implant. PMID- 1288578 TI - Family functioning during a critical illness: a systems theory perspective. AB - In this article the effects of critical illness on family functioning are described within a systems theory framework. As identified in the literature, family vulnerabilities and strengths that impede or support family functioning during the time a member has a critical illness are discussed. Strategies that nurses can use to assist families of critically ill patients are explored. A challenge to expand family-centered care across various settings is extended. PMID- 1288577 TI - Overview of contemporary families. AB - Perceptions and definitions of the term family have always been varied and complex. Hence, an overview of contemporary families is presented here from several perspectives. First, families as they have been perceived by nursing and social science theorists are reviewed. Demographic changes in the family over the last two decades are then presented, followed by an examination of issues faced by families as they change over time. Finally, families as they exist within varying cultural and social contexts are discussed. Emphasis is placed on the need for health care providers to be flexible in defining and working with individual patients and their families. PMID- 1288579 TI - Caring for parents of critically ill infants and children. AB - This article provides an overview of the literature reviewing the stresses and needs of families of critically ill children. These needs and stresses are summarized and organized to provide a framework for the research-based standard of care that is presented for parents of critically ill children. PMID- 1288580 TI - Needs of children during the critical illness of a parent or sibling. AB - The needs and significance of well children in the family typically have not been considered when addressing family-centered care. Health care providers and overstressed parents may have little awareness of or insight into the needs and concerns of these children. Without informed and sensitive interventions, however, these children may be at risk for significant long-term negative effects. This article discusses some of the needs and responses of well children who have a critically ill parent or sibling. Using a developmental framework, the author suggests interventions that may benefit these often forgotten but very vulnerable family members. PMID- 1288581 TI - Needs of adult family members after critical illness: prescriptions for interventions. AB - Concerns for family members of critically ill patients are evident in nursing literature; however, assessment parameters and intervention strategies during the critical care experience require further consideration. This article reviews the results of prior published and unpublished nursing research pertaining to needs of adult family members after critical illness. Selected nursing interventions are provided to encourage practitioners and researchers to develop, test, and evaluate those activities that most effectively meet various types of family member needs. PMID- 1288582 TI - Needs of the family during critical illness of elderly patients. AB - Persons 65 years of age or older occupy 46% of all intensive-care beds. This number will rise in the next decade as the percentage of persons age 65 or older rises to a projected 13% by the turn of the century. Elderly patients require care that may be different from their younger counterparts. The needs of the families of the elderly may also be different. Nurses should carefully consider the needs and differences of each family, especially the need to participate in care and to be with the elder and the needs for information, reassurance, and comprehensive discharge planning. PMID- 1288583 TI - Comparison ratings of need importance after critical illness from family members with varied demographic characteristics. AB - This descriptive study compares ratings of importance of selected needs by family members after the first 3 days of critical illness with family member age, gender, relationship to patient, prior intensive care unit experience, and patient medical diagnosis. Family-need importance ratings from 905 subjects, collected by 27 nurse investigators in 15 states over a 10-year period (1980 to 1989) were used as an aggregate data base. Bivariate t tests and analysis of variance procedures were used to compare ratings of importance for support, comfort, information, proximity, and assurance needs with family member demographic characteristics. Results indicated that there were more similarities than differences on the ratings of importance for selected needs from various family members. Focusing on these similarities should be useful for developing and testing nursing interventions to help family members meet their needs after a critical illness event. PMID- 1288585 TI - Visiting critically ill adults: strategies for practice. AB - Visitation and proximity needs are consistently rated as very important by families of critically ill patients. This article reviews the literature on the proximity needs of families, presents nursing interventions to meet them, and suggests a plan for future research in this area. PMID- 1288584 TI - Need for information. Interventions for practice. AB - Information is an important need of families of critically ill patients. Meeting this need requires a multidisciplinary approach and an environment that values the delivery of humanistic care. Critical care nurses require special skills in assessment, planning, intervention, and evaluation to effectively meet the information needs of families. Research is available to guide nurses in meeting the family's need for information. PMID- 1288586 TI - Support and reassurance needs: strategies for practice. AB - Support and personal needs have been empirically validated as two of the most important family need categories during critical illness. Perhaps over-shadowed during the initial critical care phase by a need for relief of initial anxiety and reassurance of quality care and information, support needs emerge as family members recognize the impact of the stressful illness experience on themselves. Critical care nurses can provide social support to family members through family assessment, counseling, and support groups. Although not empirically tested, it is generally believed that such support will influence the ability of family members to provide support to the patient and thereby influence a positive recovery from critical illness. PMID- 1288588 TI - Invasive hemodynamic monitoring in pregnancy. AB - When the pregnant woman develops an acute or critical illness requiring invasive hemodynamic monitoring, it is imperative to consider physiologic changes that occur during pregnancy that impact on assessment parameters. Awareness of both the alterations in these parameters and the changes in arterial blood gas values guide nursing care that continues to support perfusion and oxygenation needs unique to pregnancy. When critical care capabilities are not available in the labor and delivery unit, the obstetric patient is most often transferred to a medical or surgical intensive care unit. In such cases, consultation with obstetric staff is warranted. PMID- 1288587 TI - Needs of families of critically ill patients: state of the science and future directions. AB - This article provides an overview of the needs of families of critically ill patients and offers suggestions for future research. Continuous, systematic study about the needs of families of critically ill patients is necessary for nursing to be responsive to the health care needs of society in the 21st century. PMID- 1288589 TI - Cardiac disease in pregnancy: intrapartum considerations. AB - Impressive changes in the maternal cardiovascular system occur in response to pregnancy. The patient with normal cardiac function complies with these physiologic changes without difficulty. The patient with cardiac disease, however, may be at significant risk for morbidity and mortality when faced with these changes. Knowledge of the disease process is essential, because caring for the pregnancy patient with known cardiac disease presents a unique challenge to the critical care nurse. PMID- 1288590 TI - Amniotic fluid embolism. AB - Pulmonary embolism is the leading cause of maternal death in the United States. Amniotic fluid embolism (AFE) represents the least preventable and most lethal of complications with a reported mortality of 86% and an associated fetal demise of 50%. Although it is widely accepted as a clinical entity, AFE is incompletely understood. A combination of clinical presentation, laboratory findings, and exclusion of other pathologies leads to the diagnosis of AFE. The mainstays of treatment are oxygenation, maintenance of cardiac output, and correction of coagulopathy. The prognosis for the patient experiencing AFE remains bleak because it is largely unpredictable and, except for supportive measures, cannot be corrected. PMID- 1288591 TI - Management of the intrapartum patient in the intensive care unit: preparing for delivery. AB - Caring for a critically ill obstetric patient requires a thorough understanding of both the pathophysiology of the disease and the physiologic changes that accompany pregnancy and childbirth. This article addresses the care of an intrapartum patient in an intensive care unit. Physiologic aspects of the labor and delivery process are reviewed with emphasis on nursing assessments and interventions. Additionally, techniques for delivery of the neonate are presented. PMID- 1288592 TI - Legal and professional issues in critical care obstetrics. AB - The practice of critical care obstetrics is a challenging specialty that presents unique problems and issues in providing perinatal care. With the emergence of critical care obstetrics comes increased accountability and expanded responsibilities. This article addresses the legal and professional issues related to critical care obstetrics. PMID- 1288593 TI - Physiologic changes of pregnancy: impact on critical care. AB - Critical care nurses must have knowledge of normal physiologic changes during pregnancy to assess the obstetric patient appropriately. Multiple adaptations occur during pregnancy that place the woman at risk should medical or obstetric complications occur. At no time in a woman's life does she undergo the vast system changes that she experiences during pregnancy and the postpartum period. PMID- 1288595 TI - Fetal surveillance in the intensive care unit: understanding electronic fetal monitoring. AB - Electronic fetal monitoring has become an integral component of current obstetric nursing care. The goals of surveillance are to establish fetal well-being and identify the fetus at risk for asphyxia and death. Fetal heart rate (FHR) responses provide a cardiovascular indication of fetal acid-base status. To evaluate FHR tracings and plan care accordingly, the nurse must understand the physiologic regularity mechanisms of the fetus, baseline patterns, and periodic changes of the fetal heart rate. PMID- 1288594 TI - Pregnancy-induced hypertension: understanding severe preeclampsia and the HELLP syndrome. AB - Pregnancy-induced hypertension (PIH) is a multisystem disease with life threatening complications requiring expert nursing and medical management. Nurses caring for critically ill patients with this disease must be knowledgeable about the pathophysiologic occurrences of PIH as well as the protocols for anticonvulsant and antihypertensive therapy. This article presents the hemodynamic alterations of preeclampsia, the pathophysiology of the disease, and principles of acute management. PMID- 1288596 TI - Promoting parenting: the obstetric patient in an intensive care unit. AB - The complex process of mastering the new parent role can be inhibited when the mother has a critical illness that produces barriers to parenting. It is important for nurses to recognize and eliminate common barriers to parenting that occur for the mother in the intensive care unit. PMID- 1288597 TI - Critical hemorrhage during pregnancy. AB - The major causes of obstetric hemorrhage are described, and guidelines for nursing assessment and interventions presented. Complications associated with life-threatening blood loss during pregnancy are identified as well as physiologic changes unique to pregnancy that impact on nursing care. PMID- 1288598 TI - Custom-fitted protective mouthguards. AB - Custom-fitted protective mouthguards for children and adults during sports activities can prevent or minimize traumatic dental injuries. This article reviews a method for fabrication of custom mouthguards and discusses their use. PMID- 1288599 TI - Class I composite resin restoration. AB - Composite resin materials and methods for their use have improved to the extent that long lasting Class I carious lesions on stress-bearing surfaces can be restored with predictable results. This article demonstrates a step-by-step clinical technique for placement of a Class I composite resin restoration lined with a light-hardened glass-ionomer dentin replacement foundation. Emphasis is placed on tooth isolation, thoughtful handling of the respective materials, and the importance of final sealing of the resin/enamel margins. PMID- 1288600 TI - All-porcelain labial margin for ceramometal crowns. AB - The elimination of the labiogingival metal collar of a porcelain-fused-to-metal (PFM) restoration is an attempt to achieve an improved esthetic result. In their expectation of a more cosmetic tooth restoration, patients may influence dentists to use the all-porcelain labial margin to avoid metal showing in the final restoration. Success of this type of restoration depends upon proper tooth preparation. The all-porcelain margin requires a 1.2-mm wide labiogingival shoulder of approximately 70 or 90 degrees wrapping into the interproximal area. Much of the effectiveness of the restoration depends upon the design of the metal substructure. The following change is made in the design of this substructure for this modified PFM crown: the labiogingival portion of the metal is finished back to the gingival-pulpal line angle with the metal against the axial wall being from 0.3 mm to 0.5 mm thick. This allows for 0.2 to 0.3 mm of opaque and 0.7 to 1.0 mm of shoulder porcelain. The direct lift-off technique is a useful method of achieving clinically acceptable all-porcelain margins. Such restorations may give excellent results. PMID- 1288601 TI - Effects of pH on the dentin surface. AB - A microleakage and scanning electron microscope (SEM) study was conducted in order to investigate the effects of acidic primers on prepared dentin surfaces. The microleakage study revealed that no significant differences were noted between the five materials tested in regard to leakage at enamel and dentin margins. SEM analyses revealed that the smear layers of all specimens were altered in some manner. Further long-term clinical studies should be conducted to evaluate acidic treatment of dentin. PMID- 1288602 TI - Dentin bond shear strength and microleakage for Syntac/Heliomolar: a comparison between the manufacturer's and total etch technique. AB - Recent improvements in formulation have led to significant improvements in the bond strength and clinical performance of dentin bonding agents. The growing interest in the concept of total etch prompted a comparison between manufacturer recommended procedure and that of total etch for the product Syntac. An in vitro study to examine shear bond strength to dentin and microleakage and an in vivo component to investigate the micromorphologic relationship between restoration and tissue was conducted. No statistical significance was observed in bond strength values for the nonetched versus the etched group. Significantly, however, a larger number of specimens in the nonetched group exhibited microleakage. In vivo, only the etched group exhibited a zone of hybridization although both nonetched and etched restorations showed no interfacial gaps. It was concluded that total etch does not compromise the shear bond strength of Syntac but it appears to significantly reduce microleakage possibly due to the formation of a hybrid zone and may have merit clinically. PMID- 1288603 TI - Permeability effects of two dentin adhesive systems. AB - This in vitro study evaluated the effects of two dentin adhesive systems on dentin permeability. The XR-Bonding System modifies the smear layer but does not open dentinal tubules. The Kanca or "total-etch" technique (phosphoric acid, Tenure A and B, Scotchbond 2 Adhesive) removes the smear layer and opens dentinal tubules. Despite these differences, both systems reduced dentin permeability in a similar manner. XR-Bond decreased permeability to 52% of the smear layer value, while total etching reduced permeability to 66% of that value. PMID- 1288604 TI - Three-year clinical evaluation of CAD/CAM restorations. AB - This study dealt with the clinical evaluation of 121 inlays and onlays generated from both Dicor ceramics and Vita porcelains. These two different types of ceramic materials were cemented using three different duo-cured composite resin luting agents, which differed in particle size. At the end of 3 years, no difference could be detected between the clinical performance of the Dicor and Vita restorations. Both exhibited the same degree of color matching characteristics, marginal integrity, and general clinical performance; however, seven of the restorations exhibited fracture through the isthmus, which was shown to be due to insufficient cavity depth. The balance of the restorations exhibited excellent clinical performance when evaluated against the United States Public Health Service System. PMID- 1288605 TI - Polishing composite resins. PMID- 1288606 TI - Cluster management. AB - Cluster management is a management model that fosters decentralization of management, develops leadership potential of staff, and creates ownership of unit based goals. Unlike shared governance models, there is no formal structure created by committees and it is less threatening for managers. There are two parts to the cluster management model. One is the formation of cluster groups, consisting of all staff and facilitated by a cluster leader. The cluster groups function for communication and problem-solving. The second part of the cluster management model is the creation of task forces. These task forces are designed to work on short-term goals, usually in response to solving one of the unit's goals. Sometimes the task forces are used for quality improvement or system problems. Clusters are groups of not more than five or six staff members, facilitated by a cluster leader. A cluster is made up of individuals who work the same shift. For example, people with job titles who work days would be in a cluster. There would be registered nurses, licensed practical nurses, nursing assistants, and unit clerks in the cluster. The cluster leader is chosen by the manager based on certain criteria and is trained for this specialized role. The concept of cluster management, criteria for choosing leaders, training for leaders, using cluster groups to solve quality improvement issues, and the learning process necessary for manager support are described. PMID- 1288607 TI - Case management with the nurse manager in the role of case manager in an interventional cardiology unit. AB - Varying external and internal factors are motivating changes in how physicians and nurses deliver patient care within health-care institutions. A care delivery system that has received increasing attention in the literature is case management. This chapter describes how a community hospital implemented case management for patients undergoing percutaneous coronary angioplasty and cardiac catheterization while developing the new role of clinical manager to serve in the role of case manager. The process for planning and implementing such a role change is discussed, and initial evaluative data are presented. PMID- 1288608 TI - Nurse clinician model of managed care. AB - Many different models of delivering nursing care have been proposed, each with specific advantages and disadvantages. One such model, the nurse clinician model, uses the strengths of advanced clinical practice as the cornerstone for improving quality in patient care. The increase in quality simultaneously produces an efficient and cost-effective system, as indicated by the results of a multiyear study at our institution. While other effective models exist, those that emphasize advanced clinical practice, such as the nurse clinician model, are most likely to achieve improved patient outcomes and conserve resource expenditures. PMID- 1288609 TI - Case management in the neonatal intensive care unit. AB - This article will provide the reader with an overview of the concept of case management as it is used by the neonatal nurse practitioner in a neonatal intensive care unit. The role of the neonatal nurse practitioner as a case manager will be compared and contrasted to the roles of the primary nurse and staff nurse. The collaborative role with physicians will be described. Future directions for neonatal case management also will be addressed. PMID- 1288610 TI - Implementing managed care in a pediatric setting. AB - A challenge in the current nursing environment is the ability to provide care cost-effectively and yet achieve desired patient outcomes. The managed care delivery system facilitates achievement of these goals. The system incorporates management of time, resources, and personnel so that patient outcomes are achieved within appropriate time frames. This article describes the design and implementation of a managed care delivery system in a children's hospital. PMID- 1288611 TI - Use of patient care extenders in critical care nursing. AB - This article explores the implementation and use of patient care extenders in two critical care units. Experimentation and diversity in changing the care-delivery system were the forces motivating the management team to redesign the existing nursing care-delivery system. The impetuses for the change process were the use of the role of the registered nurse and cost containment. Two case studies will illustrate from a practical perspective how the change occurred. Although the same nurse manager was responsible administratively for the two units, the patient care extender models were implemented differently. This was based on the conviction that each unit is unique with regard to patients and staff needs. The first case study occurred in an 18-bed cardiac telemetry unit in which the patient extender care model was integrated with direct patient care activities of the unit. In the second case study, which occurred in a ten-bed cardiac care unit, the patient care extender was integrated with indirect patient care activities. The approach to this article is practical, and it is intended for units that may be dealing with these issues in these changing times in health care. PMID- 1288612 TI - On the essential integration of nursing and informatics. AB - This paper asserts that nursing knowledge is fundamentally inseparable from the strategies and structures that represent it. Nursing informatics comprises a new disciplinary focus that results from a blend of nursing and informatics. The technologies of informatics, communications, computer science, decision science, human information processing, and knowledge engineering, provide critical care nurses with the support necessary for contemporary nursing practice. Informatics technologies enable nurses to communicate, process knowledge in new and more efficient ways, and better understand the nature of nursing thinking. PMID- 1288613 TI - Image analysis of Artemia salina ribosomes by scanning transmission electron microscopy. AB - A dedicated scanning transmission electron microscope (STEM) at Brookhaven National Laboratory was used to visualize unstained freeze-dried ribosomal particles under conditions which considerably reduce the specimen distortion inherent in the heavy metal staining and air-drying preparative steps used in routine transmission electron microscopy (TEM). From high-resolution STEM images it is possible to determine molecular mass and the mass distribution within individual ribosomal particles and perform statistical evaluation of the data. Analysis of digitized STEM images of Artemia salina ribosomes provided evidence that a standard preparation of these eukaryotic ribosomes consists of a population of heterogenous particles. Because of the integrity of rRNAs established by agarose gel electrophoresis, variations in the composition and structure of the 80S monosomes and the large (60S) and small (40S) ribosomal subunits, as monitored by their mass, were attributed to the loss of ribosomal proteins, from the large subunits in particular. These results are relevant not only to the degree of ribosomal biological activity, but should also be taken into consideration for particle selection in the reconstruction of the "native" eukaryotic ribosome 3-D model. PMID- 1288614 TI - The Staphylococcus aureus alpha-toxin channel complex and the effect of Ca2+ ions on its interaction with lipid layers. AB - Using the techniques of two-dimensional crystallization on supported lipid bilayers together with computer image processing, two distinct two-dimensional crystal types of staphylococcal alpha-toxin complex are formed depending on the presence or absence of Ca2+ ions. Without Ca2+, these are hexagonally packed (in A, a = b = 89.5 +/- 2.5 A; theta = 119.7 degrees) With Ca2+ present, rectangular crystal packing is seen (in A, a = 114.8 +/- 1.6 A, b = 140.2 +/- 0.7 A; theta = 89.1 degrees). A third, banded crystal type is also seen which is interpreted as a side-to-side packing of regular tubules. We use these tubular crystals for cross-correlation searches with top and side-on views of the complex from single particle reconstructions, and with the repeating units from the two-dimensional crystal types. The results lead us to propose a model in which the different two dimensional crystal types are formed as a result of alpha-toxin hexamers packing in different orientations. In the hexagonal crystals the hexamers lie end-on with a 6-fold axis in projection. On the addition of Ca2+, the hexamers reorient to lie tilted with respect to the support, thus giving rise to a rectangular projection. PMID- 1288615 TI - Characterization of the conformational change in the M1 and M2 substates of bacteriorhodopsin by the combined use of visible and infrared spectroscopy. AB - A combination of visible and Fourier transform infrared (FTIR) spectroscopies is used to characterize the formation of the M1 and M2 substates of the bacteriorhodopsin photocycle in glucose-embedded, hydrated thin films. Difference FTIR bands in the amide I region verify the previously reported existence of a significant peptide backbone conformational change in the transition from M1 to M2. The visible absorption spectra demonstrate that contamination of the M intermediate samples by L, N, or other non-M species should contribute negligibly to the observed changes in the amide I region, and this conclusion is supported by comparison of specific carboxyl group peaks with corresponding bands in published L and N FTIR difference spectra. Based upon spectroscopic results, an extension of the C-T Model (Fodor, S., Ames, J., Gebhard, R., van den Berg, E., Stoeckenius, W., Lugtenberg, J., and Mathies, R. (1988) Biochemistry 27, 7097 7101) is presented. The results of this work suggest that protein structural changes should be clearly visible in M-bR, difference Fourier density maps and that these structural changes may in turn elucidate how bacteriorhodopsin actively pumps ions across the purple membrane of Halobacterium halobium. PMID- 1288616 TI - Projection map of tubulin in zinc-induced sheets at 4 A resolution. AB - Tubulin polymerizes into two-dimensional, crystalline sheets in the presence of zinc ions. These sheets are well suited to structural studies by electron crystallography. We have developed conditions for forming sheets which are large and well ordered enough to provide both electron diffraction and image data to better than 4 A resolution. In projection maps calculated from this data, the alpha and beta monomers can be identified within the protofilaments. These results indicate that we should be able to determine the structure of tubulin in these sheets at atomic resolution. PMID- 1288617 TI - EM investigation of myoblast origin in regenerating hamster skeletal muscle explants. AB - This study attempted to dispel the confusion that exists in the understanding of the origin of myoblasts during muscle regeneration. Regenerating hamster muscle explants from cultures were studied under the EM on 4 consecutive days, after incubation. Preincubation specimens served as controls. Revelations were that euchromatic myonuclei underwent dense granulation and activation after incubation. Presumptive myoblasts (PM) lying clearly within the myofibre increased in numbers with incubation time. Some myonuclei showed partial transformation towards a PM. This study concluded that myonuclei transformed into myoblasts during the process of muscle regeneration and that the PM, produced from a myonucleus, was a stage in the development of the satellite cell (SC) in regenerating muscle. These SC, myoblasts from myonuclear origin, proliferated, fused, and formed multinucleate myotubes that matured into myofibres which replaced damaged muscle. Findings of this study may have new implications for the proposed myoblast transplant or gene transfer therapy, both of which, whilst being possible answers for muscular dystrophy, depend on a sound knowledge of muscle regeneration mechanisms. PMID- 1288620 TI - Strengthening of epidemiology in Central America. PMID- 1288618 TI - Localization of a sequence motif complementary to the nuclear localization signal in proteasomes from Thermoplasma acidophilum by immunoelectron microscopy. AB - A sequence motif complementary to the nuclear localization signal (NLS) has been localized in proteasomes from Thermoplasma acidophilum by immunoelectron microscopy using sequence-specific antibodies. The antibodies were generated in two different ways: by immunization with a carrier-coupled peptide and by isolation of the sequence-specific antibody from an immune serum against native proteasomes using a peptide-affinity column. The sequence specificity of the isolated antibody was confirmed by a PEPSCAN-ELISA performed on overlapping nonapeptides deduced from the sequence of the alpha-subunit of the Thermoplasma proteasome. Compared to the antibody induced by the carrier-coupled peptide this antibody fraction showed a much higher affinity for native proteasomes. The attachment site of the Fab portion of the antibody to the proteasome was mapped by electron microscopy in conjunction with image processing. The antibody was found to bind to the periphery of the two outer "disks" of the proteasome complex formed by the alpha-subunits. PMID- 1288619 TI - Electron microscopy of thin-sectioned three-dimensional crystals of SecA protein from Escherichia coli: structure in projection at 40 A resolution. AB - SecA is a single-chain, membrane-associated polypeptide (102 kDa) which functions as an essential component of the protein export machinery of Escherichia coli. SecA has been crystallized from ammonium sulfate as small, three-dimensional bipyramidal crystals (0.1 x 0.1 x 0.05 mm). These crystals did not demonstrate detectable diffraction of X-rays from rotating anode sources. For study by electron microscopy, individual crystals were cross-linked in glutaraldehyde and OsO4 solutions, dehydrated, embedded in epoxy resin, and sectioned normal to crystallographic axial directions inferred from the external morphology of the crystals. Fourier transformation of processed images of untilted thin sections stained with uranyl acetate and lead citrate show reflections extending to 31 A resolution. Diffraction data and reconstructed images of the projected density of the unit cell contents indicate that the bipyramidal SecA crystals belong to orthorhombic space group C222(1) with unit cell dimensions a = 414 A, b = 381 A, and c = 243 A. Filtered images and density maps of mutually orthogonal projections of the unit cell contents are consistent with a three-dimensional model in which the asymmetric unit contains eight SecA monomers. The large unit cell dimensions and packing of protein monomers suggest that SecA is crystallizing as an oligomer of either dimers or tetramers. PMID- 1288621 TI - Cholera in Guyana. PMID- 1288622 TI - Lillie Shortridge. PMID- 1288624 TI - AIDS nursing: risk or ignorance is no excuse. New HIV/AIDS subspecialty program. PMID- 1288623 TI - Nursing, women, and politics. PMID- 1288625 TI - The making of an AIDS nurse. PMID- 1288626 TI - Message from the dean. PMID- 1288627 TI - Boyz 'n girlz in the hood. PMID- 1288629 TI - Advanced certificate programs. PMID- 1288630 TI - The School of Nursing, 1976-1985. Once grand and glorious. PMID- 1288628 TI - Technology Learning Center: tender loving care. PMID- 1288631 TI - Is there a doctor of nursing science in the house. PMID- 1288632 TI - Electroporation and electrofusion in cellular and viral biology. PMID- 1288633 TI - [Unconventional culture of the human hepatitis B virus (HBV)]. AB - The investigation of the key stages of the HBV vital cycle was realised recently through an unconventional cultivation technique, using transfection with an adequate DNA, cloned in plasmids. Transfections was achieved in cell lines, differentiated or not. The results showed that expression of some of the HBV genes is under the control of hepatospecific factors. PMID- 1288635 TI - Approximate formulae (deduced from a mathematical model) for the characteristics of the interepidemic and epidemic periods of some virus diseases. AB - By a qualitative analysis of the solutions of the mathematical model equations (describing the morbidity and susceptibility evolution in a viral epidemics), approximate formulae for the extreme values of the variables and for the duration of the main phases of a multiannual cycle are deduced. These formulae were validated by numerical simulation of the solutions, leading to the exact values of the mentioned essential characteristics of the diseases propagation. PMID- 1288634 TI - [The possibility of the vertical intrapartum transmission of the HIV and HB viruses]. AB - A study was performed on 756 serum samples collected from the umbilical cord of newborn infants. HBV markers were found in 4.63% of the tested subjects. Of these samples, 291 were tested for the HIV markers and 0.34% were found positive (versus 0 in the controls, most of them men from the same region). Results confirmed the possibility of vertical transmission of both viruses, HBV and HIV, in Romania. PMID- 1288636 TI - [The demonstration by immunofluorescence of inframicrobial antigens on samples of peripheral blood vessels (artery and vein) from subjects with different vascular diseases]. AB - The presence of fourteen inframicrobial agents was investigated by the immunofluorescence technique using specific antisera on 345 samples of arteries and veins collected during operation from patients with chronic vascular diseases (arteritis, varicosity) and on 50 samples of umbilical cord. Results indicated a positivity rate of 75.45%; most of the cases had associations of two to five antigens. Coxsackie A virus and mycoplasmas were the agents most frequently found. PMID- 1288637 TI - Complement fixing antibodies against selected viruses in diabetic patients and non-diabetic control subjects in Ibadan, Nigeria. AB - Sera of forty insulin-treated Nigerian diabetics attending the outpatients clinic of the University College Hospital (U.C.H.), Ibadan, and an equal number of non diabetic control subjects matched for age, sex and social status were tested for presence of complement fixing (CF) antibodies against five viruses: Coxsackie A and B1, mumps rubella and enterovirus group antigen. Antibody levels to Coxsackie B1, mumps, rubella and enterovirus did not show any significant difference between the two groups (P > 0.05). The serum levels of antibody to Coxsackie A virus were significantly higher in non-diabetic controls than in the diabetics (P < 0.05). Previous exposure to these viruses may not be a significant factor in the aetiology of insulin dependent diabetes mellitus in this environment. PMID- 1288638 TI - The distribution of nucleic acid chromophores at cellulose-water interfaces. 1. Photometric parameters. AB - A computer-assisted calculus of the chromophores distribution in the contiguous layer around the scattering centers of a multiple scattering medium, using bichromate photometric data and an extended Kubelka-Munk expression, was developed. Explanatory examples of nucleic acid impregnated chromatography paper disks show the efficiency of the method proposed for the study of macromolecular structures and the dependence upon the physico-chemical peculiarities of the solutions used. PMID- 1288639 TI - [The electrophoresis of biotinylated nucleic acids]. AB - A simple and rapid method was worked out to evaluate the biotinylation level of the pBR322 and pSVK1H genetic cloning vectors, using gel electrophoresis. Avidin was used to slow down the migration of biotinylated DNA: the DNA migration speed diminished as the biotinylation level rose, due to DNA complexation. The highest level of biotinylation is characterized by the formation of a biotinylated nucleic acid-avidin complex with no electrophoretical mobility. PMID- 1288640 TI - Some seroepidemiological data on HIV-antibody and HBs-antigen prevalence in children and infants of Craiova (Romania). AB - By testing 2362 children and infants from Craiova (Romania), for both HIV antibody and HBs-antigen presence in the blood, a high rate of positivity was noticed in orphanages and in dystrophia units. A rate of "signal" (i.e. about 4% for HIV-antibodies, and 2.5% for HIV-antibody/HBs antigen), in hospitalized patients (pediatric service), was found as well. Four reasons support the horizontal way of virus transmission as the main route: most of seropositive subjects belong to 1-to-3-year age range, suggesting a virtual contamination before introduction of disposable syringes in Romania care units and hospitals; many HIV-seropositive cases have received frequent parenteral treatments, during repeated hospitalizations for acute respiratory disease; only few of the mothers of seropositive infants exhibited HIV-antibody presence; a relatively high rate of "double" seropositivity, i.e. HIV-antibody/HBs antigen, within tested serum samples was noticed. PMID- 1288641 TI - HIV-antibody detection in children by competitive and direct micro-ELISA techniques. AB - A comparative study was carried out on 110 sera from children or infants, suspected of HIV-antibody presence following several micro-ELISA assays, using four direct micro-ELISA (Wellcozyme HIV 1 + 2, Rapid Elavia Mixt, Ortho Diagnostics, RECVIH) and a competitive system--Wellcozyme-Recombinant. In three of the four direct systems, as well as in the competitive system, significantly higher mean values of sample/cut off, and cut off/sample ratios, respectively, as compared to the direct systems RECVIH, were present. High optimal levels of sensitivity and specificity (%), as related to Western Blot results, were found with Wellcozyme direct and competitive kits, as well as with Rapid Elavia Mixt kit, as compared to lower levels exhibited by the other two direct system kits (Ortho Diagnostics an especially RECVIH). As regards three Western Blot undetermined results, obtained in patients with a severe clinical state and evolution to exitus, by comparing some serological markers of HIV infection in two serum samples belonging to the same case (second sample collected 4 weeks after collection of the first homologous sample), the disappearance of gag encoded-p24 band in Western Blot, associated with negativation of HIV-p24 antibody and with the presence of free virus antigen in all three second serum samples occurred, that would reflect a probable fall of immune anti-HIV "barriers" during final stages of illness. Although Western Blot confirmation cannot be excluded, it seems to be useful to assay comparatively HIV-antibody presence by means of direct and competitive micro-ELISA systems, in the same serum sample. PMID- 1288642 TI - The evolution of hepatitis B virus infection in children with symptomatic AIDS. AB - Hepatitis B virus (HBV) markers were determined in 80 children under 5 years of age with HIV symptomatic infection. Because of high carrier rate of hepatitis B virus in Romania we investigated as control a group of age matched 36 HIV negative children offsprings of HBsAg carrier mothers. Serological and epidemiological investigations in families of HIV infected children support horizontal nosocomial and not vertical transmission for HIV in contrast with HBV whose perinatal transmission can not be excluded. Concerning the probable route of HBV infection both groups of children seem to have a comparable risk for parenteral, contact-associated or maternal-neonatal transmission. HBsAg was detected in 76.25% HIV positive subjects and in 13.9% of control (P = 0.05). From all serum samples tested, only 12, all from the control group, did not present any markers of past or current HBV infection. Two serum markers have been used as an index of active HBV replication: HBe antigen detection and HBs antigen quantification in one or paired serum specimens. HBeAg was detectable in 20% of HIV infected children and only in 2.8% controls (P = 0.05). Almost all HBeAg positive patients have higher values for HBs antigenemia. HBsAg concentrations well above the assay cut off value (sample/cut off ratio > 15) were generally representative for HIV infected children (54% versus 5.6% in controls). The prevalence of hepatitis Delta markers and anti-HCV antibodies was not significantly higher in HIV infected children in spite of the fact that they are potentially exposed to a wider range of antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288643 TI - [The processing of experimental tabulated data with the standardized Multiplan and VU-CALC programs]. AB - The possibilities are investigated of processing data tables issued from immunofluorescence tests for quick virologic diagnosis, from fluorimetric determinations and from spectrophotometric evaluation of electrophoregrams of serum samples from patients with or without hepatitis. Analysis was realised using microcomputer programs facilities. PMID- 1288644 TI - [The hepatitis D virus and its role in the evolution of hepatitis B]. PMID- 1288645 TI - Biological roles of HIV Nef proteins. A minireview. AB - The nef gene, its protein products and diverse mechanisms by which HIV pathogenicity is nef-mediated in vivo and in vitro explain the huge amount of works on this topic. Until now the following functional roles have been assigned for nef: 1. downregulation of virus replication; 2. GTP binding and GTPase activities; 3. modulation of cytoplasmic signalling; and 4. cellular (CD4 and IL 2) gene regulation. Many reports which demonstrate the possible functions of nef in viral replication and in development of AIDS have been refuted by other scientists who failed to confirm some biological activities. Host immune response against nef proteins has been claimed as an early diagnosis marker or to be involved in disease progression. Also, nef proteins have been involved in blocking of HLA antigens, in superantigen production or in crossreactivity with some cellular antigens. The role of nef is a complex one, important in establishing and maintaining viral latency in vivo and regulating virus replication in vitro. PMID- 1288646 TI - Pharmacological agents used in implant dentistry. PMID- 1288647 TI - Advanced periodontitis treated with osseointegrated implants. PMID- 1288648 TI - The electro-milled fixed-removable implant prosthesis. PMID- 1288649 TI - The edentulous mandibular arch. Part II. The fixed-detachable prosthesis treatment option. PMID- 1288650 TI - Three unit bridge using a natural tooth shouldered abutment. PMID- 1288651 TI - Assessment of the accuracy of cytology in women referred for colposcopy and biopsy: the results of a 1 year audit. AB - The results of weekly colposcopy review meetings have been audited for 1 year and cases where there was a discrepancy between the referral cervical smear and the initial colposcopy biopsy have been analysed. New referrals (n = 476) for colposcopy were studied. In the final outcome 80% of 326 women referred for moderate or severe dyskaryosis were found to have cervical intraepithelial neoplasia (CIN) grade II or III or invasive carcinoma. Three women found to have invasive carcinoma had been referred for severely dyskaryotic smears. Twenty women were referred for smears with cell changes suggesting glandular neoplasia: five were found to have adenocarcinoma in situ, whereas eight had CIN and seven had negative biopsies. The results justify the referral policy and demonstrate the need for further investigation when initial colposcopic biopsies are negative. PMID- 1288652 TI - Cost effectiveness of a fine needle aspiration clinic. AB - The resource implications of a Fine Needle Aspiration (FNA) Clinic at Northampton General Hospital have been evaluated over a 12 month period using a patient management questionnaire. A total of 490 cases from which fine needle aspirates were taken from superficial sites have been assessed (breast 381, thyroid 46, lymph node 44, salivary gland 9, soft tissue 10). Total resource savings (135,544 pounds) exceeded the expenses of the FNA clinic (27,290 pounds). Potential cost savings per case were the greatest for thyroid aspirates. The FNA clinic where the pathologist takes, stains and reports optimally prepared specimens, provides a high quality and accurate service on which clinicians can confidently base clinical management decisions. Unnecessary investigations and operations are avoided, allowing scant resources to be released for other procedures. PMID- 1288653 TI - Inflammatory lesions of the breast: diagnosis by fine needle aspiration. AB - Amongst 1061 breast lesions diagnosed by fine needle aspiration (FNA) over a period of 6 years (1985-1990), 128 were reported to be showing changes consistent with an inflammatory lesion. On review, the cytodiagnosis was found to be inaccurate in 31 cases. The cytological features of the 97 cases that were correctly reported are described in this report. The cytological diagnoses issued in these 97 cases were acute mastitis or breast abscess (57 cases) and tuberculous mastitis (30 cases). Non-specific chronic mastitis and miscellaneous conditions accounted for four and six cases respectively. Acid fast bacilli (AFB) were demonstrated in 28.0% of tuberculous mastitis cases and 10.0% of those diagnosed as acute mastitis or breast abscess. FNA cytology was found to be useful for the diagnosis of inflammatory lesions of breast and their classification, as only five out of 57 cases of acute mastitis/breast abscess and one out of 30 tuberculous mastitis cases were suspected on clinical grounds. PMID- 1288654 TI - Brush cytology technique in the detection of oesophageal carcinoma in the asymptomatic, high risk subject; a pilot survey. AB - This study assesses the reliability of abrasive brush cytology in the diagnosis of early cancer of the oesophagus among asymptomatic rural Ciskeians. An inexpensive locally manufactured brush biopsy capsule was used to obtain cytological material from 1336 subjects; 59% of them were brushed a second time. The technique appears to have a high sensitivity (90%) and specificity (99.9%). Three of five asymptomatic subjects diagnosed as having early oesophageal cancer refused further treatment, indicating the importance of health education as a prerequisite to the introduction of a screening programme for oesophageal cancer. PMID- 1288655 TI - Identification of malignant cells in serous effusions using a panel of monoclonal antibodies Ber-EP4, MCA-b-12 and EMA. AB - A panel of three monoclonal antibodies (MoAbs) was tested on 29 benign and 53 malignant effusions with the aim of investigating its usefulness for the discrimination between benign and malignant lesions. The panel consisted of MoAbs directed against epithelial membrane antigen (EMA); MCA-b-12, reacting with a 350 kD glycoprotein with mucin-like characteristics present on human breast cancer cells and various other normal and neoplastic tissues, and Ber-EP4, directed against a 34 and 39 kD glycopeptide on human epithelial cells but not on mesothelium. Fifty-two (98%) of the malignant effusions reacted with EMA, 49 (92%) with MCA-b-12 and 44 (83%) with Ber-EP4. Fourteen per cent of benign effusions reacted with EMA, 17% with MCA-b-12 and 7% with Ber-EP4. All seven effusions obtained from patients with a malignant mesothelioma reacted with EMA, six of the seven cases staining intensively. None of the seven stained with Ber EP4. MCA-b-12 did not react with the cells in one case of malignant mesothelioma. The results suggest that the combination of EMA and Ber-EP4 may be used to discriminate between benign and malignant cells and possibly also between adenocarcinoma and malignant mesothelioma. MCA-b-12 followed in general the reaction pattern of EMA, although often with a less intense staining reaction, making this antibody unsuitable for inclusion in the panel. PMID- 1288657 TI - The Lensman microscope: tool or toy? AB - The experience of using the Lensman microscope for 1 year indicates that this inexpensive, pocket-sized instrument, which can be used at the bedside or in the outpatient department, can assess the quality of needle aspirates although it is not suitable for making definitive cytological diagnoses. PMID- 1288656 TI - The British Society for Clinical Cytology Certificate of Competence in Cytology Screening: a report of the first 3 years' experience. AB - In 1988 the Department of Health (DOH) recognized the cytology screener grade of laboratory staff. Cytology screeners have a 2 year training period after which they must sit a 'competence examination'. The British Society for Clinical Cytology offers an examination to meet the DOH specification. It consists of a written paper, a practical screening test, a spot test and a short viva voce. The screening test is paramount and candidates who miss a dyskaryotic smear cannot be successful. In the first 3 years there have been 22 examinations, 294 candidates and a pass rate of 76%. The majority of candidates were Cytology Screeners of 2-3 years experience but significant numbers of Medical Laboratory Scientific Officers (MLSOs) and senior MLSOs also chose to sit the examination. PMID- 1288659 TI - The 1991 IPA Research Awards in Psychogeriatrics. PMID- 1288658 TI - Fine needle aspiration cytodiagnosis of apocrine carcinoma of the breast. AB - The cytopathological appearances of 14 cases of apocrine breast carcinoma diagnosed by fine needle aspiration cytology are described and the features compared to those seen in apocrine cells aspirated from benign cystic and solid lesions. Significant atypia must be observed before a diagnosis of apocrine carcinoma can be entertained. PMID- 1288660 TI - The evolution of dementia in idiopathic Parkinson's disease: neuropsychological and clinical evidence in support of subtypes. AB - One hundred and seven newly diagnosed, untreated patients with Parkinson's disease (PD) were divided into two groups according to their age at reported onset of symptoms. Of these, 79 patients were under age 70 (early-onset) and 28 patients were age 70 and over (late-onset). The group of 50 control subjects comprised spouses, friends of the PD patients, and community volunteers. The patients were participants in a multicenter drug study of Parkinson's disease. Each had received a detailed neurological and neuropsychological assessment in the baseline placebo phases of the study. Thirty-4 patients with early-onset and 12 patients with late-onset were reassessed 3 years after treatment with low-dose levodopa, with bromocriptine, or with a combination of the two drugs. The results of the baseline phase of the study revealed that 8% of the early-onset group and 32% of the late-onset group were classified as demented. The 3-year follow-up revealed that the prevalence of dementia had increased to 17% in the early-onset group and to 83% in the late-onset group. This study confirms that at least two distinct subtypes of Parkinson's disease exist. The subtypes differ both clinically and neuropsychologically. The age at onset of symptoms is a critical determinant of the rate and type of cognitive decline in Parkinson's disease. PMID- 1288661 TI - Behavioral syndromes in Alzheimer's disease. AB - The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment. PMID- 1288662 TI - Cross-cultural variations in depressive symptoms in later life. AB - The purpose of this study is twofold: to estimate the prevalence of depressive symptoms among older adults in four culturally diverse groups (white Americans, black Americans, Japanese, Taiwanese), and to assess whether there are cross cultural variations in the way depressive symptoms are manifest. Data from three recent nationwide surveys in the United States, Japan, and Taiwan reveal that the lowest overall levels of depressive symptoms are found among Japanese elderly, followed by Taiwanese, white Americans, and black Americans respectively. Based on previous cross-cultural research, it was hypothesized that the Japanese tend to express depressive symptoms as interpersonal complaints, whereas Taiwanese are more likely to manifest somatic symptoms. In contrast, Americans were expected to express depressive symptoms in the form of depressed cognitions. The findings failed to support these hypotheses. Instead, older Americans tended to have higher scores than Orientals on all three depressive symptom clusters. PMID- 1288663 TI - A new systematic method of measurement and diagnosis of "mild cognitive impairment" and dementia according to ICD-10 and DSM-III-R criteria. AB - Normative data were collected in a study population of 150 randomly selected elderly subjects. Using the SIDAM (Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, multi-infarct dementia, and dementias of other etiology according to DSM-III-R and ICD-10), both the dimensional and the categorical aspects of dementia and "mild cognitive impairment" are considered. With the SIDAM score (SISCO) [range 0 (minimum)-55 (maximum, no cognitive impairment)] and the SIDAM Mini-Mental State Examination (MMSE) (range 0-30), appropriate cutoffs for the category of DSM-III-R and ICD-10 dementia and "mild cognitive impairment" were defined. MMSE scores of 0-22 were found to be indicative of DSM-III-R and ICD-10 dementia. For "mild cognitive impairment," MMSE scores ranged from 23-27 according to a DSM-III-R definition (ICD-10: 23 28). An MMSE score of 22 or less was found to differentiate between DSM-III-R/ICD 10 dementia and "mild cognitive impairment," with a specificity of 92% (ICD-10: 95.6) and a sensitivity of 96% (ICD-10: 96%). With the SIDAM-based DSM-III-R/ICD 10 diagnoses of dementia as the criterion, the SISCO was 97.3% specific (ICD-10: 99%) and 94% sensitive (ICD-10: 94%) in detecting dementia. A SISCO of 0-33 was highly indicative of DSM-III-R and ICD-10 dementia. For "mild cognitive impairment," a SISCO between 34-47 (ICD-10: 34-51) was found. The SISCO covers a broader range of cognitive functions than the MMSE and is more useful in detecting even very mild cognitive decline. Furthermore, the newly defined category of "mild cognitive impairment" could be validated successfully by means of GDS Stages 2-3 and CDR Stage 0.5. These findings confirm the value of the SIDAM as a short diagnostic instrument for measurement and diagnosis of dementia and "mild cognitive impairment." PMID- 1288664 TI - Agitation in elderly persons: an integrative report of findings in a nursing home. AB - Agitated behaviors in the nursing home pose a major problem for caregivers. Our data showed that the three syndromes of agitation--aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors--are differentially related to medical and psychosocial variables. Physically nonaggressive behaviors may be adaptive for a resident who presents a deteriorated stage of dementia, since these behaviors offer stimulation and exercise. Verbally agitated behaviors may be a form of help-seeking behavior for residents with physical disease and depressed affect. Aggressive behaviors are those least understood, although these behaviors correlate with advanced stages of dementia and with poor interpersonal relationships. These findings should be a basis for further studies, with the ultimate goal being improved care for agitated elderly persons. PMID- 1288665 TI - Toward an understanding of cognitive functioning in geriatric depression. AB - This paper addresses the questions of whether depression compromises cognition in the elderly and whether discernable patterns of cognitive performances could be differentiated between patients with severe depression and those with organic dementia. Published data on geriatric depression and cognitive functioning are divided in demonstrating a depression effect. Further examination and external validation by new data show that the depression effect on discrete cognitive tasks is (1) small, and (2) sensitive to the confounding of sampling and task variables. Future research must take these factors into account. Patterns of cognitive functioning in depression and dementia are different and can be differentiated using a variety of measures. This review finds the term pseudodementia inappropriate and misleading and recommends that it be abandoned. PMID- 1288666 TI - Relationships among an older adult's life review, ego integrity, and death anxiety. AB - The frameworks of Erikson (1963) and Butler (1963) were used to design this descriptive study that investigated the relationships among life review, ego integrity, and death anxiety in older adults. Three hypotheses were proposed: (a) the greater the life review, the higher the ego integrity; (b) the greater the life review, the lower the death anxiety; (c) the higher the ego integrity, the lower the death anxiety. The sample consisted of 115 female and male volunteers between the ages of 65 and 93. The participants filled out the Life Review Questionnaire, Adult Ego Development Scale, Death Anxiety Scale, Death Preparation Scale, and a Personal Information Sheet. Life review, while not positively correlated with ego integrity, was found to have a negative correlation with death anxiety. Also, religious subjects were found to be more prepared for death than those who did not practice. Implications for therapy and future research are discussed, as well. PMID- 1288667 TI - Examining key variables in selected reminiscing modalities. AB - This study examined the underlying variables of selected reminiscing processes to determine those that contributed to well-being. Two hundred and forty subjects randomly selected from nursing homes and high-rises participated in one of 10 different reminiscing modalities for eight weeks. Measures of life satisfaction (LSI-A), psychological well being (ABS), self-esteem (SES), and depression (BDI) were given pre- and postintervention to determine the most therapeutic treatment modalities. Results showed the most therapeutic way to reminisce was through a structured, evaluative life review performed on an individual basis. Thus, three variables contributed to successful reminiscing: individuality (one-to-one reminiscing), evaluation (a personal valuing of events), and structure (covering the whole life span). PMID- 1288668 TI - A strategy of "combination chemotherapy" in Alzheimer's disease: rationale and preliminary results with physostigmine plus deprenyl. AB - Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer's disease, there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis. This report focuses on the concept of "combination chemotherapy" in Alzheimer's disease as the next generation of therapeutic strategies. Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor, 1-deprenyl, the authors speculate that a combination of physostigmine, the short-acting cholinesterase inhibitor, and 1 deprenyl might be more beneficial than either agent alone. The authors outline a sample paradigm for such combination studies, report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl, and point to other possible "combination chemotherapy" strategies for future study. PMID- 1288669 TI - The integrated health-care system: reflection and projection. AB - This paper presents a personal view of the development of integrated, comprehensive health-care systems in the United States. The influence of Federal legislation is described, beginning with the 1950-60s policy objective of Hill Burton Program administrators to create a number of community-based regional medical centers, each consisting of a range of health services organized by and around community hospitals. Later variations of the concept appeared in such programs as Medicare-Medicaid, Comprehensive Health Planning, the Regional Medical Programs, and the new Agency for Health Care Policy and Research. Based on the cumulative experience of the past, the economic, professional and social climate of the present, with its increasing involvement of the patient/payer/consumer in decisions, and the enhanced inter-organizational coordination emerging from technologies of computers and communication science, the goal of creating comprehensive integrated systems as conceived in the 1950s and 60s may finally be achieved in the 1990s, but in a different form from that envisioned earlier. By judicious exploitation of computer and communication capabilities and the massive knowledge bases evolving from research, the way is eased for patient-centered integration and coordination of services without demanding integration in the sense of ownership or formal control of all the providers within a central organization. PMID- 1288670 TI - A historical review of the Kaiser Permanente Medical Care Program. AB - The Kaiser Permanente Medical Care Program evolved from a series of major construction projects in the 1930s and from the World War II shipyards in the early 1940s. In the late 1940s, it became a community-based medical care program, and later in the 1970s, the prototype Health Maintenance Organization (HMO). Over the past five decades, Kaiser Permanente has developed its basic principles of prepaid, group practice for comprehensive-care services where physicians control their medical practice in a partnership of responsibility for the Health Plan, the Hospitals, and the Medical Groups. All of this is carried out with autonomy of its 13 regions in the United States. PMID- 1288671 TI - Health systems education yesterday, today, and tomorrow. AB - This paper traces the history of the application of industrial management engineering techniques to health systems problems. The educational background of early practitioners and the development of specialized health systems educational programs are described. Projections are made about the future of health systems engineering and health systems education. PMID- 1288672 TI - Systems approaches in emergency medical services: the history, the impact, and the future. AB - Systems approaches have been important in planning and evaluating emergency medical services (EMS) systems. However, maximal use of systems approaches are limited by small political boundaries, the lack of user-friendly systems tools, and the need for EMS planning staffs who are familiar with these systems tools. Developing technology, particularly communications, will continue to have a great impact on EMS delivery. In addition, the need is seen for continuing advances in systems concepts, and in particular, the promotion and incorporation of health and prevention of injury as systems concepts. PMID- 1288673 TI - Hospital payment based on diagnosis-related groups. AB - The Prospective Payment System (PPS) used by Medicare to pay hospitals is described. As Diagnosis-Related Groups (DRGs) are central to this system, they are described in some detail. While the results achieved by PPS have been impressive, opportunities to both improve and extend the approach are present. Problems with the approach are described, together with alternatives to direct payment. PMID- 1288674 TI - Clinical information systems: 25-year history and the future. AB - Clinical information Systems have not advanced rapidly enough to meet the growing needs for clinical data. This is due primarily to the industry's past focus on financial information processing. Pressure is increasing for clinical data to support health-care professionals in the delivery of patient care, and in the establishment and monitoring of quality of care indicators. This article summarizes the history of clinical systems, and presents key issues regarding future clinical information systems. PMID- 1288675 TI - The origins of hospital microcosting. AB - This paper begins with a definition of microcosting, including the specification of design criteria and a general model framework. The necessity for micro- as opposed to macro-costing is discussed. Examples of microcosting systems are provided. Relative value scale and case-mix alternatives to microcosting are presented. PMID- 1288676 TI - Nurse staffing and scheduling: past solutions and future directions. AB - Nurse staffing and scheduling systems have been a significant challenge for operations researchers, industrial engineers, and system developers for many decades. The purpose of this paper is to discuss historical approaches to workload measurement, nurse staffing and personnel scheduling, and to predict possible future directions for nurse staffing and scheduling systems. PMID- 1288677 TI - Patient-scheduling methodologies. AB - Inpatient admissions, surgical scheduling, and outpatient scheduling are three of the most important patient-scheduling functions in the hospital. In this paper, the key elements of state-of-the-art scheduling systems are discussed, along with a rationale for their importance. Our purpose is to show how well-designed patient-scheduling systems can contribute to the improvement of hospital operations. PMID- 1288678 TI - [Sympathetic control of spontaneous cardiac defibrillation]. AB - The parameters of transmembrane potentials of cardiomyocytes and dynamics of fibrillation process have been investigated when altering the level of sympathetic action on the heart by injection of rausedile, katecholamines and by stimulation of the nucleus of hypothalamus. It was shown that the injection of rausedile decreases rest potential and potential activity, meanwhile electrical irritation significantly increases the period of spontaneously reversible fibrillation. PMID- 1288679 TI - [The adrenergic regulation of cardiomyocyte electrophysiological activity, cardiac biochemical function and coronary blood flow in rats with incorporated 131I]. AB - The study was made of the rat heart isolated according to Langendorf and right auricles. Intraperitoneal injections of 2.5 MBq/kg 131I were performed. Electrophysiological and biomechanical myocardium response to stimulation of alpha and beta-adrenoreceptors with isoprenalin and phenylephrine hydrochloride was analyzed. Postradiation modification of adrenergic control in animals with incorporated 131I appeared as reduced functional response of cardiomyocytes and intact heart to beta-adrenoagonist and enhanced response to alpha-agonist was detected. PMID- 1288680 TI - [The effect of leucine enkephalin on the development of a convulsive afterdischarge in the sensorimotor cortex of rats]. AB - The application of leucin-enkephalin solution (LEU) (2 micrograms/2 microliters) on stimulated region of sensomotor cortex did not influence threshold of direct and transcallosal cortex responses (DR and TCR). On coupling of repeated electrostimulation train (RET) (duration of impulse--0.1 ms; duration of train- 10 s; frequency--10/s) with application of LEU (after every odd train) the changes of DR and TCR in course of even trains and latency of afterdischarge appearance were such as in control ones. Simultaneously LEU effectively depressed short posttetanic potentiation of DR and TCR and potentiation of amplitude and duration AD, evoked by RET. It is suggested that LEU released from neurons in the course of RET does not participate in initiation of seizure in sensomotor cortex. A possible role of LEU in sensomotor cortex is limitation of intensity and duration of seizures and prevention of status epilepticus. PMID- 1288681 TI - [The mechanism of the action of dalargin in experimental myocardial ischemia]. AB - In acute experiments on cats it has been shown that dalargin possess antiarrhythmic affect in myocardial ischemia. Antiarrythmic effect of dalagrig may be connected both with reflex and with direct action of dalargin on neurons structure, which PMID- 1288682 TI - [Microfluorimetric research on the erythroblastic islands and macrophages of the bone marrow]. AB - A microfluorimetric system was used to study rat bone marrow erythroblastic islands (EI) and macrophages. Measurement of fluorescence from acridine-orange treated cells was performed on the microscope LUMAM-E3 (LOMO, Leningrad) at 530 550 and 630-650 nm. The intensity of fluorescence in 530-550 nm range depended on the intensity of proliferative processes in EI, that at 630-650 nm was associated with activity of lysosomal apparatus of EI macrophages. Erythroblast amplification in EI is parallel both to enhancement of fluorescence intensity at 530-550 nm and 630-650 nm. Intensity of fluorescence of different bone marrow macrophages was evaluated. It is suggested that a part of bone marrow macrophages has high affinity to erythroid tissue. PMID- 1288683 TI - [Sex differences in the cholinergic status of white rats]. AB - Female rats injected with organophosphate inhibitor of acetylcholinesterase chlorophose at doses of 10 mg/kg and 360 mg/kg showed less considerable decrease in blood acetylcholinesterase activity than did male animals. Females compared with males also demonstrated less expressed clinical symptoms of poisoning (salivation, convulsion) after injection of chlorophose at dose of 360 mg/kg. The value of LD50 in female rats was 860 mg/kg, whereas the comparable value in male animals was 700 mg/kg. Following the injection of atropine at doses of 0.1, 0.3, 0.6 mg/100 g female rats showed 2-3 fold increases in basal adrenal and plasma corticosterone levels, but significant decreases in stress-induced corticosterone levels. As for males, the basal and stress-induced values of corticosterone were not significantly affected by atropine administration. These results suggest that functional reserves of cholinergic system and responsiveness of the hypothalamic pituitary-adrenal axis to cholinergic influence are greater in females than in males. It is concluded that cholinergic status is significantly higher in female rats than in male ones. PMID- 1288684 TI - [Sex differences in adrenocortical sensitivity and resistance to cerebrovascular damage in rats under strong stress]. AB - Dynamics of changes in adrenal and plasma corticosterone and the development of cerebrovascular lesions were studied in both male and female rats, exposed to strong stress (combined immobilization and intermittent found sound for 2 hours). Plasma corticosterone levels in stressed females were 460% and 660% of the control values when measured on stress minute 10 and 120. The corresponding values in male rats were 220% and 360%. The stress-induced dilatation of brain vessels and the increases in vascular permeability were less pronounced in females than in males, when studied 0.1 and 24 hours after termination of stress. The number of brain perivascular haemorrhages was markedly reduced in females compared with males. It is supposed that higher resistance to stress-induced cerebrovascular lesions in females may be attributed to higher functional reserves of steroidogenesis. PMID- 1288685 TI - [The reactivity of the skeletal muscle arterioles of rats to noradrenaline after whole-body gamma irradiation at a dose of 1 Gy]. AB - Male Wistar rats were exposed by total gamma-irradiation at 1 Gy, Reactions of skeletal muscle arterioles and mean arterial pressure on intravenous doses of noradrenaline (0.1, 0.3, 1.0 and 3.0 micrograms/kg) was studied by intravital microscopy in acute experiments 1, 3 and 5-6 days after irradiation. The exposure causes arterial hypotension on day 1 after that as well as marked reduction of spontaneous arteriole vasomotions and decrease of arteriole constrictions at any doses and dates under study. There are no differences of arterial pressure reaction amplitudes in per cent between control and exposed animals at any doses and dates under investigation. PMID- 1288686 TI - [The effect of low-intensity laser radiation on blood metabolic indices in the postresuscitation period]. AB - The effect of He-Ne laser radiation (632.8 nm; 0.3 mW/cm parallel to oxygenation on metabolism indices of blood, taken in early postresuscitation period after discontinuation of hemorrhagic shock was studied in vitro. Compared to oxygenation alone, combined therapy resulted in more marked oxygen consumption of the blood, normalization of plasma antioxidant total activity, superoxydismutase erythrocyte catalase activity, the number of double connections in fatty acid chain of general lipids and membrane viscosity were elevated. Regular dependence of lipid peroxidation on a number of metabolic blood parameters is revealed. PMID- 1288687 TI - [The mechanism of the steric exclusion of cells brought about by proteoglycans]. AB - The effect of amount of rabbit erythrocytes and concentration of sodium hyaluronate and sodium salt of protein--chondroitin-keratan-sulfate were studied on aggregation of erythrocytes suspended in 0.15 M NaCL, pH 7.4. It was shown that the rate of steric exclusion of erythrocytes depends on relationship between amount of erythrocytes and concentrations of these proteoglycans. PMID- 1288688 TI - [The antiepileptic effects of sodium valproate and the calcium antagonist riodipine when used jointly in a model of focal penicillin-induced epileptic activity]. AB - In experiments on 52 freely moving Wistar male rats, 200-220 g in weight, on the model of focal penicillin-induced epileptic activity (EpA) in brain cortex the efficacy of combined application of drugs influencing different mechanisms of epileptogenesis: sodium valproate enhancing GABA-ergic processes, and the calcium antagonist ryodipine (1,4-dihydropyridine) have been studied. It was shown that valproate and ryodipine when used in combination at relatively small doses (150 and 0.8 mg/kg l.p., respectively) produced a more marked antiepileptic effect than each of these drugs given alone. These and previously reported results of studies on the model of generalized pentylenetetrazol-induced EpA, suggest that complex pathogenic therapy (CPT) as a combination of the antiepileptic drugs acting on the corresponding basic pathogenic mechanisms of respective form of epilepsy is reasonable to be used. CPT allows to obtain a better curative effect with a lower dose of each drug used and to reduce the risk of side effects of the drugs applied at large doses in case of monotherapy. PMID- 1288689 TI - [The biochemical parameters of the brain and disordered conditioned reflex activity in orchiectomized rats]. PMID- 1288690 TI - [The antidepressive properties of anaprilin]. AB - After chronic administration of propranolol (1 and 5 mg/kg, 14 days) to rats time course of forced swimming changed with the decrease of rhythmical index of depression. The drug attenuated depressogenic properties of reserpine and clonidine. Propranolol antidepressive activity is attributed to blockade cerebral adrenoreceptors. PMID- 1288691 TI - [The antiepileptic effects of sodium valproate and the calcium antagonist riodipine when used jointly in a model of generalized korazol-induced epileptic activity]. AB - In experiments on male Wistar rats on the model of generalized pentylenetetrazol induced epileptic activity the efficacy of the combination of the drugs influencing different mechanisms of epileptogenesis: sodium valproate enhancing GABA-ergic processes and calcium antagonist, ryodipine (1,4-dihydropyridine), have been studied. Sodium valproate and ryodipine when used in combination at relatively small doses (70 and 0.75 mg/kg, respectively) produced more marked antiepileptic effect than each of these drugs given alone. The results obtained suggest that complex pathogenetic therapy (CPT) as a combination of antiepileptic drugs acting on corresponding basic mechanisms of respective form of epilepsy is reasonable to be used. According to our previous results, CPT can reduce the risk of side effects of each drug due to decreased doses. CPT may be of great importance in case of long-term treatment. PMID- 1288692 TI - [Cerebokrast as a corrector of postischemic phenomena in acute transient cerebral ischemia]. AB - Acute cerebral ischemia in cats (both carotid arteries occlusion during 30 min after permanent occlusion of both vertebral arteries) was accompanied by postischemic hypoperfusion and hypo-oxygenation of the cerebral tissue. Intravenous infusion of cerebrocrast (1 micrograms.kg-1.min-1 during 60 min) prevented manifestation of the postischemic phenomena. Antihypoxic effect of cerebrocrast involved the cerebral blood flow increase, brain oxygen consumption lowering and Hb-O2-affinity decrease. PMID- 1288693 TI - [The effect of calcium antagonists on blood deoxygenation processes]. AB - The effect of verapamil, nifedipine and sensit on the whole rat blood deoxygenation was studied by polarographic coulometry with consequent calculation of deoxygenation rate (DR) and blood deoxygenation constant (BDC). These drugs were studied in concentrations 10(-8)-10(-4) M according to their therapeutic range in vivo. Both verapamil and nifedipine significantly decreased DR, and the latter drug decreased BDC as well in concentration 2.9.10(-7) M. In contrast to verapamil and nifedipine, sensit caused mild, but statistically significant dose related increase in DR with concomitant decrease in BDC. The data presented failed to establish relationships between chemical structure and deoxygenative effect of the drugs. Deoxygenation effect of sensit favours its administration in the treatment of ischemia-related arrhythmias. PMID- 1288694 TI - [The effect of a high external temperature on cellular immunity]. AB - The study was made of spleen cells proliferative response to mitogens PHA, Con A or alloantigens in relation to hyperthermia effects. Acute hyperthermia (rectal temperature 42 degrees) enhanced lymphocyte function, proliferative responses to allo-antigens, PHA and Con A increased. Thermal shock was associated with suppression of the spleen cell response. Mice suffering from hyperthermia for 20 min (43-44 degrees) daily during 10, 20 and 30 days showed suppressed T-cell immune response. Normal splenocyte proliferation recovered 40 days after hyperthermia induction. PMID- 1288696 TI - [The effect of recombinant interleukin-2 on the course of experimental staphylococcal peritonitis in mice]. AB - The effect of RIL-2 on the survival of mice with S. aureus--induced peritonitis was studied. Animals received bacterial suspension and RIL-2 as following: bacteria--on days 0, +2, RIL-2--day 0 (group 1); bacteria--days 0, +4, RIL-2- days 0, +2 (group 2); bacteria--days 0, +6, RIL-2--days 0, +2, +4 (group 3). RIL 2 exerted no protective effect in group 1. However, in groups 2 and 3, where the control animals survival was, resp., 56% and 38%, the RIL-2 treatment increased survival up to, resp., 84% and 70%. Antibiotics given instead of RIL-2 in analogous regimen decreased the survival in group 3 to the level of 25%. Thus, RIL-2 proved to be a potent therapeutic agent in the 2nd of 3d studied models of S. aureus--induced peritonitis in mice. The perspectives of RIL-2 use in the treatment of bacterial peritonitis, including porous ones, and of the immunodepression--aggravated conditions are discussed. PMID- 1288697 TI - [The immunomodulating properties of the diuretic bufenoks]. AB - Bufenox, a diuretic with a sodium-uretic and light potassium--uretic effect, has an immediate but short-term effect, stimulates IgM antibody production, depressed delayed-type hypersensitivity. The immunomodulating effect of bufenox may be due to changes in Na+ ions concentrations since sodium load abrogates immunoactive properties of the drug. PMID- 1288695 TI - [The prophylactic administration of interleukin-2 increases the survival of mice with an acute intra-abdominal infection caused by Staphylococcus aureus]. AB - The effect of RIL-2 on the survival of mice with acute Staphylococcus aureus strain 5/2 intra-abdominal [correction of intraperitoneal] infection was studied. RIL-2 was ineffective when administered simultaneously with the LD100 dose of bacteria. Antibiotics (gentamycin or combination of penicillin and streptomycin) administered in the same fashion cured 100% of animals. However, RIL-2 proved to be effective when administered simultaneously with LD70 dose of bacteria. The prophylactic course of RIL-2 consisting of repeated injections on days 3, 2 and 1 before the challenge with LD100 dose of bacteria also resulted in the marked increase of the survival of mice. The hypothetical mechanisms of action and the prospects of RIL-2 application are discussed. PMID- 1288698 TI - [The effect of dalargin on stress-induced changes in the 5'-nucleotidase activity of the macrophages and in the level of endogenous blood cortisol in mice]. AB - The action of dalargin, synthetic analogue of leuenkephaline, on stress-induced changes in 5'-nucleotidase activity and endogenous hydrocortisone levels was investigated in mice. It was found that there is a direct relation between the activity of 5'-nucleotidase and the level of hydrocortisone in CBA mice. For C57Bl/6 mice the relation was inverse. Dalargin is able to change the dependence from direct to opposite in CBA mice. PMID- 1288700 TI - [The effect of intra-articular emoxipin injections on the course of immune arthritis in rabbits]. AB - Immune arthritis in sensitized rabbits was induced by intraarticular injection of bovine serum albumin. The development of the arthritis was accompanied by an increase in ESR, a rise of the level of serum CRP, caeruloplasmin and CIC. A chemiluminescent response of the whole blood phagocytes to stimulation by barium sulfate crystals, serum beta-glucuronidase and red cell superoxide dismutase activity enhanced, plasma malone dialdehyde content rose, serum SH groups diminished. PMID- 1288699 TI - [The antimicrobial cationic proteins of the neutrophilic granulocytes in experimental Q rickettsiosis]. AB - Blood of 56 guinea pigs with experimental Q rickettsiosis was studied cytochemically (lysosomal cationic test) to measure the level of cationic proteins in neutrophil granulocytes. Development of Q rickettsiosis resulted in a decrease in the killing ability of neutrophils, depending on infection dose introduced. However, by day 7 of the disease, the level of cationic proteins in blood neutrophil granulocytes returned to the initial range. Similar situation was noted after subcutaneous injection of Coxiella burnetti corpuscular antigen. Subcutaneous infection with the living culture stimulus induced the wave-like decrease of the cationic proteins content. Infection of pre-immunized animals led to smaller decrease in the cationic proteins levels and to their more rapid recovery. Aspects of antimicrobial activity of neutrophil granulocyte cationic proteins in experimental Q rickettsiosis is discussed. PMID- 1288701 TI - [The detoxifying and immunocorrective properties of some sorption treatment methods in suppurative-septic poisoning in experimental diffuse peritonitis]. AB - During septic intoxication in diffuse peritonitis poisoning is accompanied by circulatory and volemic failures, considerable changes in immune status, basically of the cellular component of T-system. Several sorption methods were applied which produced different effects on the pathologic process. Extracorporeal application of spleen-xeno and ultraviolet irradiation of autoblood considerably increased the immune reactivity. Plasmapheresis and hemosorption administration had low immunocorrective effect. It is believed reasonable to employ a combination detoxication methods. PMID- 1288702 TI - [The use of flow cytofluorometry for determining antisperm antibodies by sperm immobilization and sperm toxicity methods]. AB - During antisperm antibody detection by conventional methods of immobilization and cytotoxicity investigators used flow cytometry to detect dead and/or immovable sperm cells. It was shown that after incubation of sperm cells with low antiserum dilution immovable spermatozoa are still living. Evidently, cytotoxicity test in this case brings about false-negative results. Therefore, flow cytometry will be a success for ASAB detection through immobilization test. PMID- 1288704 TI - [The biorhythms of arterial pressure in virtually healthy middle-aged men and their relationship to solar activity rhythms]. PMID- 1288703 TI - [The selective accumulation of monoclonal antibodies in the lungs after cyclophosphane administration to rats]. AB - The study has demonstrated the possibility to use cyclophosphamide as a model of "impairment" agent for lung tissue cells to provide access of monoclonal antibodies to nuclear antigen structures. Biodistribution of monoclonal antibodies to various intracellular antigens was studied on Wistar rats pretreated with various doses of cyclophosphamide. Accumulation of 2C5 antibodies to cell nuclei was found to be dependent on the dose of cyclophosphamide administered. PMID- 1288705 TI - [The evaluation of the possibility of using prodigiozan for isolating extracts that stimulate proliferative processes in the resected liver]. AB - The experiments were performed on 126 white male rats. The inclusion of 3H thymidine in nuclear DNA of the liver was studied on h 24 and 48 after 70% resection of the liver versus prodigiosan injection or combination of prodigiosan with 70% resection of the liver. Liver extracts stimulating proliferation (ESP) obtained under the above schedules were studied on the model of 30% liver resection. It is shown that prodigiosan (0.25 mg/kg) injected to intact rats and rats with 70% resected liver initiated ESP production promoting the inclusion of 3H-thymidine in nuclear DNA of the liver after 30% resection of the liver. PMID- 1288707 TI - [A morphological study of rat liver cells after the administration of phenobarbital and ziksorin]. AB - Male Wistar rats were inducted with phenobarbital and ziksorin. The inducing effect has been shown by hepatocyte hypertrophy involving the cytoplasm and nuclei. After phenobarbital injection cytoplasmic hypertrophy was due to redistribution of the plastic material in favour of the smooth-surface endoplasmic reticulum (SER). This redistribution occurred with the decrease of the energy forming and external synthetic functions of hepatocytes. After ziksorin injection SER hyperplasia was combined with proportional hyperplasia of the whole cytoplasmic organelles of the liver cells. This points to more optimal response of hepatocytes after ziksorin induction as compared with phenobarbital. Therefore, ziksorin can be recommended for clinical practice if it is necessary to stimulate processes of reparative regeneration in the liver. PMID- 1288706 TI - [The insulin-secreting and proliferative activity of established islet cells in the presence of sulfonylurea]. AB - Exponentially growing rat islet cells (RINr) and hamster islet cells (HIT T-15) were incubated in presence of tolbutamide (10-1000 microM), gliclazide (0.1-10 microM) or glibenclamide (0.01-10 microM) for 15 hrs. Accumulation of insulin in culture medium was estimated by RIA. Effects of sulfonylureas (SU) on cell proliferation were assessed by 3H-thymidine (3H-T) incorporation into cellular DNA. All of SUs used stimulated insulin production in RIN and HIT cell cultures (with an exception of tolbutamide, which markedly suppressed insulin secretion in HIT cells at 1000 microM). 3H-T incorporation into RIN cells was elevated only in presence of gliclazide (10 microM), whereas tolbutamide at 1000 M significantly inhibited RIN cell proliferation. Gliclazide (0.1 microM) and glibenclamide (0.01 10 microM) enhanced 3H-T incorporation into HIT cells. Further detailed investigations of mechanisms of SU effects on islet cell reproduction will be of use for designing optimal strategy of hypoglycemizing therapy of diabetes mellitus. PMID- 1288708 TI - [The modelling of cerebral ischemia in dogs with pathological kinking and occlusion of the carotid arteries]. AB - An experimental model of brain ischemia in pathological kinking and occlusion of carotid artery has been developed on 40 dogs. Each model was documented angiographically, controlled with radionuclides, evaluated morphofunctionally. Basing on the results, surgical indications for correction of brachiocephalic artery lesions are provided. PMID- 1288709 TI - [The characteristics of the hemodynamics and oxygen regimen of the rat uterus]. AB - For biomicroscopic study of architectonic and hemodynamic features of uterine vascular bed wide ligation was carried out. It is shown that the vascular bed serves for blood deposition with cyclic change of inflow and outflow intensity. A rhythmic hypoxia results in a decrease of PO2 in the myometrium. The revealed biorhythm is considered evolutionary, determining physiological mechanism of plastic supply of generative function and development of the fetus resistance to hypoxia. PMID- 1288710 TI - [The morphofunctional characteristics of the cecum in experimental influenza]. AB - On the model of experimental influenza using morphological, immunomorphological, cytochemical, electron microscopy and morphometric methods, the authors provided morphofunctional characteristics of the caecum, showed the progression of infectious process and confirmed the dissemination of the virus, availability of virus particles in different cell populations, among them in lymphoid cells. PMID- 1288711 TI - [The characteristics of the morphofunctional status of the adenohypophysis in lethally irradiated recipients after bone marrow transplantation]. AB - The effect of lethal irradiation and transplantation of syngenic bone marrow in a dose of 1 x 10(7) cell/ml on the morphofunctional state of hypophysis at various stages of the posttransplantation period has been studied for 3 months using 100 linear male mice of a F1 (CBA x C57 B) line. The experiments conducted have shown that bone marrow transplantation reduces the intensity of the negative effect of irradiation on hypophysis and facilitates normalization of its histological structure. There was a correlation between changes in the number of secretory cells in the anterior lobe of the hypophysis and the level of corticosterone in irradiated and bone marrow-protected animals. PMID- 1288712 TI - [The morphofunctional characteristics of the thymus in rat fetuses and progeny in venous occlusion]. AB - Using histological and morphometrical methods, morphofunctional state of the thymus was studied in fetuses and offspring of rats in physiological pregnancy and under conditions of phlebo-occlusion. Phlebo-occlusion resulted in hypertrophy of the fetus, thymus and offspring, changes in structural zones and cellular reactions. PMID- 1288713 TI - [The morphogenetic patterns of the higher autonomic centers in a pathological pregnancy]. AB - Neurosecretory, parasympathetic and sympathetic centers of 49 mature fetuses subjected to toxicity were studied using light and electron microscopy. These centers were characterized by similar regularities of neurocytes development. Higher degree of maturity was typical for neurosecretory, while minimal for sympathetic centers. A higher degree of maturity and functional performance of vegetative regulatory system predominated in large fetuses. A general rule was a relative independence of forming truncal and spinal morphosystems and their nuclei on body and brain masses. Dyschronia of vegetative centers development reduces an adaptive potential of the fetus and causes fatal outcome in intranatal period. PMID- 1288714 TI - [The characteristics of thrombocyte morphological structure in patients with endogenous depression during antidepressant therapy]. AB - The study of platelets surface in patients with endogenous depressions made before the beginning of therapy, 1-3 days later and during the first days of clinical recovery with scanning electron microscopy showed that the platelets of patients who had not received antidepressants were activated. More marked activation took place after long-term therapy in the form of platelets with distinct pseudopodia, which were 2-3 times longer than cells body and with inclination to form large aggregations. This cell type is also characterized by formation of a new type of rod platelets. It is suggested that antidepressants accumulation takes place on cell membrane during long-term therapy that causes selective or general increase of membranes permeability, cytotoxicity. PMID- 1288715 TI - [The effect of chemical damage to the adrenal cortex on its ontogenetic development]. AB - We studied adrenal gland of rats at the age of 1 month, which underwent injections of dioxin-preparations during a week. In 1, 6, 12 days; 1, 3, 5, 5, 7, 13 months adrenal gland mass, adrenal cortex size, adrenocorticocytes number, 3B ol-steroid dehydrogenase and succinate dehydrogenase activities of the experimental animals differed greatly from that of the control. It was found that chemical damage of the gland at an early stage changes it greatly during the following ontogenic development. PMID- 1288716 TI - [The use of cryopreserved arteries as arterial vascular prostheses]. AB - The aim of the study is investigation of possibility to bypass small and medium size arteries with cryopreserved artery allografts, storing 7-10 days at -196 degrees C under the protection of 15% dimethylsulfoxide. In experiments on 40 rabbits were placed a region of the left renal artery by cryopreserved bioprosthesis. Graft patency was 80% after observation up to 6 months. By angiography it was 8 cases of graft thrombosis (all during the 1st week after implantation) and 5 cases of moderate graft dilation (in 4 of them it was accompanied with stenosis of distal anastomosis). In 20 dogs we replaced a region of the femoral artery by cryostoring bioprosthesis. It was only one case of graft thrombosis which occurred on month 2 after the implantation during 1-year follow up. After 3 months in 3 cases there developed 3 cases of diffuse narrowing of graft lumen without decreasing of blood flow through the prosthesis. Later, the graft lumen did not change. Histological investigations have revealed a viability of cryopreserved vessels, its almost complete de-endothelialization at 3 days and total re-endothelialization 2 weeks after implantation. During the first 2 weeks there were morphological events of graft rejection, which disappeared after 3 months. PMID- 1288717 TI - [The role of dyslipoproteinemia in the genesis of chronic hepatitis]. AB - The dynamics of structural changes in the liver in experimental dyslipoproteinemia (DLP) and its correction was studied. Vessel-tissue changes found in the liver of rabbits in a short-term and stable DLP (4, 8 weeks) can be estimated as different stages of chronic active hepatitis. The microcirculation disorders and structural changes in the liver appeared at the early stages of DLP in the absence of atheromatosis in large arteries. The pathological changes in the liver existed 36 weeks after the rejection of atherogenic diet and correlated with DLP. Thus, DLP can be the risk factor as cardiovascular diseases as chronic nonspecific changes in the target organs. PMID- 1288719 TI - [The morphofunctional characteristics of the cecum in experimental escherichiosis]. AB - Using the model of experimental escherichiosis in mice by means of morphological, immunomorphological, morphometrical and electron microscopy methods, the authors give morphofunctional characteristics of caecum 15 minutes to 2 weeks after inoculation. The authors show the dynamics of infectious process, characterized by changes of microcirculation, increasing lymphoplasmocellular infiltration, dystrophic changes in cells of neuroplexes and degranulation of mast and endocrine cells. The data obtained show that pathological process in caecum during experimental escherichiosis has an immune character, that the above portion of the intestine is a part of endocrine system. PMID- 1288718 TI - [The morphological changes in the erythrocytes and in the blood iron level of rats under the action of E. coli endotoxin]. AB - Development of endotoxin shock in rats is accompanied by decreasing dry mass and content of dense substances in red blood cells. Endotoxin reduces circulating iron concentration as well. During endotoxin administration morphological changes of erythrocytes become stable, appearance of echinocytes promotes elevation of hemostatic potential and enhancement of blood cells aggregability. PMID- 1288720 TI - [Nursing: a caring science with a distinct domain]. PMID- 1288722 TI - [Clients' individual well-being as a goal in nursing]. PMID- 1288723 TI - [Nurses in key positions]. PMID- 1288721 TI - [Nursing care following bypass surgery]. PMID- 1288724 TI - [Professional organizations as an influence]. PMID- 1288725 TI - Pituitary tumors: diagnosis and treatment. AB - This article reviews the current general approach to the biochemical diagnosis and the treatment of pituitary tumors with special reference to medical treatment with dopamine agonists and somatostatin analogs. Dopamine agonists are the treatment of choice in patients with prolactin producing tumors. Octreotide is a major advance in the adjunctive treatment of growth hormone producing tumors. Trans-sphenoidal surgical decompression remains the primary treatment modality in gonadotrofinomas, clinically non-functioning pituitary tumors and thyroid stimulating hormone (TSH) producing tumors. Adrenocorticotrophin (ACTH) producing tumors are treated primarily by selective adenomectomy. The biochemical diagnosis of Cushing's syndrome is complex. Bilateral inferior petrosal sinus sampling for ACTH measurement is highly reliable in the differential diagnosis of ACTH dependent Cushing's syndrome, but needs expertise. PMID- 1288726 TI - Neurotoxicity of interferon-alpha. AB - Interferon (IFN) related neurotoxicity includes somnolence and confusion, fatigue, lethargy, psychiatric symptoms, conceptual disorganization, neurological deficits, cortical blindness, coma and, rarely, death. The neurologic syndromes seem to be more common in elderly patients, following intramuscular or intravenous administration, at higher doses of frequent injections of IFN-alpha and in primary renal cell carcinoma. The duration of the treatment was not strongly related to neurotoxicity. Computed tomography findings were non-specific and included atrophy or periventricular lucencies. Electroencephalograph studies demonstrated a generalized increase in slow wave activity which returned to normal after cessation of treatment. Behavioral and mental changes in patients treated with IFN are warning signs, and indicate the need to withdraw treatment. PMID- 1288727 TI - The impact of phase I clinical trials on the quality of life of patients with cancer. AB - This prospective, non-randomized study was designed to evaluate the quality of life (QOL) of cancer patients receiving new cytotoxic therapy. QOL was measured using a linear analog self assessment scale (LASA). Cancer patients who received a phase I agent (n = 45) had no significant changes in any of the individual QOL variables, overall QOL (p = 0.77) or performance status (p = 0.08) following one course of phase I therapy. However, patients who were not eligible for entry on a phase I protocol and who received supportive care (n = 10) experienced significant decreases in overall QOL (p = 0.02) and performance status (p = 0.003) after 1 month of follow-up. This pilot study suggests that participation in phase I trials does not adversely affect one's QOL. PMID- 1288728 TI - Evaluation of combinations of antineoplastic ether phospholipids and chemotherapeutic drugs. AB - Combinations of drugs are used clinically for the therapeutic advantages they may provide over single agents. We have studied the cytotoxic interaction between four either phospholipids ET-18-OCH3, BM 41.440, BN 52205 and BN 52211, and several chemotherapeutic drugs (ADM, CDDP, VLB, VP-16, MMC, BLM and MTX) on two human tumor cell lines, A427 (lung) and HT29 (colon). We have used the MTT colorimetric assay to evaluate growth inhibition and performed isobologram analysis on the IC50 data. For both cell lines a synergistic effect has been found between each of the four ether phospholipids in association with CDDP and ADM. In both cell lines only BM 41.440 and BN 52211 act synergistically with VLB while, in A427 cells, only BN 52205 behaves similarly with MMC. These results show that a positive interaction exists between ether phospholipids, spindle poisons and DNA-interactive drugs. PMID- 1288729 TI - Intratunical versus parenteral administration of methotrexate. AB - Methotrexate (MXT) distribution in serum, testicle and epididymis after administration into the tunica vaginalis cavity or intravenously was studied in 36 dogs. The dogs were divided into two equal groups: (1) an intratunical group in which 20 mg MXT solution was injected into the tunica vaginalis sac of each dog and (2) a parenteral group in which the same MXT dose was administered intravenously. The MXT concentration in serum, testicle and epididymis was determined 2, 4 and 24 h after MXT administration. Clinical and histologic examination of the tunica vaginalis was performed weekly for four consecutive weeks. The intratunical route, in contrast to the parenteral route, achieves a high MXT level in the testicle and epididymis with a low serum level, resulting in low toxicity and high drug efficacy. This route may therefore be suitable for a more effective treatment of testicular and epididymal lesions, notably malignant tumors. PMID- 1288730 TI - Interaction of epirubicin with other cytotoxics and anti-emetic drugs. AB - Epirubicin is usually administered in combination with other cytotoxics. Few pharmacological studies address whether relevant clinical interactions occur in vitro between these drugs. This study investigated whether epirubicin interacted with other cytotoxics or anti-emetics. The following drugs were prepared at pharmacological concentrations, etoposide (200 micrograms/ml), 5-fluorouracil (120 micrograms/ml), cisplatin (100 micrograms/ml), vincristine (100 micrograms/ml) and cyclophosphamide (1 micrograms/ml) respectively were admixed with epirubicin (1 micrograms/ml). Epirubicin was analysed by high performance liquid chromatography using in-line UV and fluorescence detectors. Experiments were performed in quadruplicate. No significant interactions were noted. The experiments were repeated for stemetil and maxolon. Maxolon did not interact with epirubicin but stemetil produced an interfering peak in the assay. We conclude that interaction studies are an important step in the workup of chemotherapy regimens. PMID- 1288731 TI - Immunomodulatory activity of two new aza alkyl phospholipid antineoplastic drugs. AB - The present work reports the modulation of immunocompetent cell functions by two aza alkyl phospholipids (AAP), BN 52205 and BN 52211. Each compound was compared with 1-O-octadecyl-2-O-rac-glycero-3-phosphocholine (ET-18-OCH3) and/or three drugs used for cancer treatment, i.e. cisplatyl (CIS), 5-fluorouracil (5-FU) and cytosine arabinoside (ARA-C). Interleukin (IL)-1 release from P388D1 cells was increased 2-fold in the presence of 5 micrograms/ml BN 52205 or BN 52211. However, these stimulations were lower than those obtained with ARA-C, 5-FU and CIS. Compared with ET-18-OCH3, CIS and 5-FU, BN 52205 and BN 52211 were more efficient in increasing tumor necrosis factor production induced by lipopolysaccharide (LPS) from human monocytes. In vitro, all compounds exhibited similar activity in enhancing IL-6 production from human monocytes stimulated with LPS, with the exception of 5-FU and CIS that were inactive. At 20 mg/kg (i.v.), a peak of IL-6 production was reached 2 h after injection of ET-18-OCH3 [> 1280 U/ml (n = 4, p < 0.001) versus 3.5 +/- 0.2 U/ml (n = 7)], whereas BN 52211 induced a maximum of IL-6 production after 4 h (77 +/- 27 U/ml, n = 5, p < 0.001). BN 52205 induced peaks of IL-6 production after 3 and 6 h (90 +/- 62 and 68 +/- 35 U/ml, respectively, p < 0.001, n = 4). The proliferation of rat splenocytes was abolished in the presence of BN 52205 and BN 52211 at 10 micrograms/ml, corresponding to only a partial reduction of IL-2 production at the same concentration. The production of interferon-gamma was stimulated 6- to 10-fold in the presence of 1-5 micrograms/ml BN 52205, BN 52211 and ARA-C. BN 52211 and BN 52205 were also potent enhancers of IL-3 production, whereas 5-FU and ARA-C were inhibitory. These results indicate that in addition to a direct antitumoral effect, AAP may also exhibit immunomodulatory activity both in vitro and in vivo. PMID- 1288732 TI - Clavine alkaloids and derivatives as mutagens detected in the Ames test. AB - Eight cytostatic clavines were investigated for mutagenicity in Salmonella typhimurium (reversion of the his-strains TA98, TA100, TA102 and TA1537), directly and in the presence of a mammalian xenobiotic metabolizing system, S9 (NADPH-fortified postmitochondrial fraction of liver homogenate from Aroclor 1254 treated rats). Four compounds (festuclavine, 17-bromofestuclavine, 1 allylelymoclavine and 1-methyllysergol methyl ether) were direct mutagens, whose activity was enhanced in the presence of S9. The other compounds (1 cyclopentylfestuclavine, 13-bromo-1-cyclopropylmethylfestuclavine, 6-cyano-1 propyl-6-norfestuclavine and 6-allyl-1-propyl-6-norfestuclavine) showed mutagenic effects only in the presence of S9, as previously observed with other clavines (agroclavine and its 1-propyl and 1-pentyl derivatives). Thus, all investigated clavines may be metabolized to mutagenic products by mammalian enzymes. Bacteriotoxic activities did not correlate with mutagenic activities. The bacteriotoxicity of several clavines was reduced in the presence of S9. The results are discussed with regard to the potential therapeutic use of clavine alkaloids as antimicrobial and antineoplastic agents. PMID- 1288733 TI - A possible modulatory influence of melatonin on representative phase I and II drug metabolizing enzymes in 9,10-dimethyl-1,2-benzanthracene induced rat mammary tumorigenesis. AB - The oncosuppressive effect of melatonin on 9,10-dimethyl-1,2-benzanthracene (DMBA) induced rat mammary tumorigenesis led us to assess its possible modulatory influence on representative hepatic and mammary drug metabolizing enzymes in DMBA treated female Holtzman rats, reared in short and long photoperiods. Melatonin treated rats in either photoperiod showed a significant induction in hepatic and mammary levels of glutathione (GSH) and cytosolic activities of glutathione S transferase (GST) when compared with the corresponding controls, along with a significant drop in hepatic microsomal contents of cytochromes b5 and P450. This induction of GSH and GST, and depletion of cytochromes b5 and P450 by melatonin may possibly be related to its anticarcinogenic potential in this tumor model. PMID- 1288734 TI - Synergistic cytotoxicity of combinations of dimethyl sulfoxide and antineoplastic agents against P388 leukemia in CD-F1 mice. AB - We have reported that dimethyl sulfoxide (DMSO) and antineoplastic agents exhibit synergistic cytotoxicity against human tumors in vitro. This study was undertaken to investigate this effect in vivo. Groups of mice were given intraperitoneal (i.p.) injections of P388 leukemia cells. Groups were treated with i.p. injections of either saline, DMSO alone, mitoxantrone hydrochloride (DHAD) alone, methotrexate alone, DHAD in DMSO or methotrexate in DMSO. Combinations of DMSO and DHAD produced 46-61% increases above expected survival, demonstrating synergistic cytotoxicity in vivo. Following confirmatory animal studies, trials utilizing i.p. delivery of antineoplastics in DMSO as treatment for peritoneal tumors should be undertaken. PMID- 1288735 TI - Bone marrow stromal cells attenuate mitoxantrone cytotoxicity against HL-60 leukemic cells. AB - We evaluated the effect of cultured human bone marrow (BM) stromal cells on the cytotoxicity of mitoxantrone (MIT) against the HL-60 leukemic cell line. BM derived fibroblastoid cells (BMFC) suppressed colony formation of HL-60 cells in the absence of MIT. BMFC increased the survival of HL-60 colony-forming cells in the presence of 50 ng/ml MIT. A significant decrease in the drug concentration was not detected on BMFC. Our results suggest that BM stromal cells can modulate the antileukemic effect of an anticancer drug. PMID- 1288736 TI - Murine macrophage activation after cisplatin or carboplatin treatment. AB - Murine peritoneal macrophages when treated in vitro with cisplatin (9 micrograms/ml) or carboplatin (50 micrograms/ml) for 2 h are stimulated to form cytoplasmic extensions seeking out tumor cells and establishing cytoplasmic connections; however, no contact is observed with normal cells (fibroblasts and hepatocytes). In addition, cisplatin and carboplatin treatment leads to an increase in the number of lysosomes and their transfer to the tumor cells resulting in lysis (as studied by confocal microscopy). Although calcium seems to be involved in the signalling of macrophage activation, cytosolic calcium does not seem to influence this activation. PMID- 1288737 TI - Activity of a chartreusin analog, elsamicin A, on breast cancer cells. AB - The in vitro activity of elsamicin A (ELS) was investigated compared with that of doxorubicin (DX) on two sensitive breast cancer cell lines: one estrogen receptor positive (ER+, MCF7) and one estrogen receptor-negative (ER-, MDA-MB-231) line, and on a DX-resistant subline (MCF7DX). The activity of the two drugs was also investigated on 19 clinical breast cancer specimens from untreated patients. The drugs were tested at pharamcologically relevant concentrations, as calculated from the area under the curve for a 3 h exposure to the lethal dose producing 10% mortality (LD10) in mice, and at 10- and 100-fold concentrations. In DX-sensitive lines, a greater inhibition of RNA and DNA precursor incorporation, as well as of cell proliferation, was caused by ELS than by DX. Moreover, the antiproliferative effect was 10-fold higher in the ER+ MCF7 than in the ER- MDA-MB-231 cell line (IC50: 0.25 versus 0.21 micrograms/ml). ELS was cross-resistant to DX in the MCF7DX subline. In clinical specimens, effects on DNA precursor incorporation were more often observed for ELS than for DX at the same drug concentrations. The in vitro sensitivity to ELS was more pronounced for ER+ than for ER- tumors: minimal inhibiting concentrations of the drug were 0.1 and 3.5 micrograms/ml, respectively, in the two groups. If confirmed in a larger series of human breast tumors, these in vitro results would indicate a promising role for ELS in clinical treatment, mainly of ER+ breast cancer patients. PMID- 1288738 TI - Methylglyoxal bis(butylamidinohydrazone) exhibits antitumor effect on human malignant melanoma cells but reduces the antitumor action of cisplatin. AB - The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyloxal bis(butylamidinohydrazone) (MGBB) on human malignant melanoma (HMG) cells and its combination effect with cisplatin were investigated. The growth of cultured HMG cells was inhibited in a dose dependent manner by either MGBB or cisplatin; complete inhibition of cell proliferation was attained with 5 micrograms/ml of MGBB or 50 micrograms/ml of cisplatin. Pretreatment of HMG cells with MGBB diminished the antitumor action of cisplatin. The cultured HMG cells were inoculated in nude mice and aliquots of the resulting solid tumors (HMG tumor) were transplanted. The growth of transplanted HMG tumors in mice was inhibited markedly by cisplatin (3.8 mg/kg) and moderately by MGBB (10 or 20 mg/kg). The in vivo antitumor effect of cisplatin was also reduced by combined treatment with MGBB. PMID- 1288739 TI - Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines. AB - Mesothelioma is a tumor of the serous surfaces in the thorax and abdomen. This tumor has proved to be exceptionally resistant to treatment, although a variety of multi-modality therapies have been tried. We have used four human mesothelioma cell lines, originating from diffuse asbestos-related malignant (pleural) mesothelioma, to assess in vitro sensitivity to five chemotherapeutic drugs, to recombinant human interferon (IFN)-alpha and -gamma and to combined immuno chemotherapy. The cytotoxic effects were assayed by vital dye exclusion. The drugs tested were etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine. The combinations tested were etoposide+cisplatin, and etoposide+cisplatin+mitoxantrone. All the drugs and combinations were also tested with recombinant human (rHu) IFN-alpha 2C (rHuIFN-alpha), rHuIFN-gamma, and rHuIFN-alpha+rHuIFN-gamma. The cell lines were most sensitive to mitoxantrone, 4 epirubicin and vindesine (TC50 < or = 0.001 micrograms/ml), and least sensitive to etoposide and cisplatin (TC50 > or = 0.1 micrograms/ml) used singly. There was no improvement in sensitivity when the drugs were combined. To further investigate the lack of response to cisplatin treatment, we examined the binding of cisplatin to the mesothelioma cell DNA. The tumor cell DNA bound markedly less cisplatin than human fetal fibroblast DNA. Three cell lines were tested with rHuIFN-alpha and rHuIFN-gamma on their own or rHuIFN-alpha+rHuIFN-gamma. They were consistently sensitive to rHuIFN-alpha, but the sensitivity to rHuIFN-gamma varied with the cell lines. Finally, we tested two cell lines with the drugs singly and in combination, together with 0.01 micrograms/ml each of rHuIFN-alpha and rHuIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288740 TI - Navoban (tropisetron) and 5HT3 antiemetics in perspective. Hotel Inter Continental, Vienna, Austria, 2 October 1992. PMID- 1288741 TI - Food for thought. PMID- 1288742 TI - An interview with ... Libby Campbell. PMID- 1288743 TI - 'Awareness'. The 8th Daisy Aryis Lecture. PMID- 1288744 TI - African diary. PMID- 1288745 TI - Change and the operating theatre nurse (2). Strategies for successful implementation of proposed changes. PMID- 1288746 TI - Care plans and me. A very personal view. PMID- 1288747 TI - Role reversal. PMID- 1288748 TI - Change and the operating theatre nurse--Part 3. PMID- 1288749 TI - Individual performance review--meeting staff needs. AB - One of the main components of job satisfaction is the recognition of one's achievements. It can be argued that nursing has been slow to recognise the positive effects of honest feedback on individual performance. Individual Performance Review (IPR) or staff appraisal is one way of providing that feedback. PMID- 1288750 TI - The first year. Professor P. Gilroy Bevan, CBE. PMID- 1288751 TI - Informed consent. An ethical dilemma? PMID- 1288752 TI - The modern treatment of menorrhagia by endometrial resection. PMID- 1288753 TI - The manager's role in developing standards. AB - Pick up any health care journal nowadays and you are bound to find at least one article on quality standards and audit. More and more professional staff of all disciplines are examining their practice and documenting standards of care which aim to promote a desired and achievable level of performance against which actual performance can be compared. PMID- 1288754 TI - A patient information guide--a necessary tool. PMID- 1288755 TI - The history of vascular grafts. PMID- 1288756 TI - Inadequate response from the FDA. PMID- 1288758 TI - The use of phenothiazines during pregnancy and lactation. PMID- 1288757 TI - The combined effects of cocaine and amphetamine on primary postnatal rat heart cell cultures. AB - Recent reports demonstrated that perinatal exposure to cocaine (Coc) and amphetamines (Amph) predisposed the infant to adverse cardiovascular consequences. Dose- and time-dependent effects of Coc and Amph on postnatal rat myocardial cell cultures are described. Contractile activity, morphology, lactate dehydrogenase (LDH) release, MTT formazan production, and neutral red (NR) retention were determined. No contractile activity was observed in cultures treated with the highest drug doses. After 24 h, the percentage of areas exhibiting contractile activity was decreased in cultures exposed to the lowest doses of both drugs. When Coc and Amph were combined, beating rates were significantly altered. Morphologic alterations were observed in all treatment groups. LDH release occurred in cultures exposed to the highest doses of both drugs. No significant differences were observed for MTT or NR. These data demonstrate that Coc and Amph doses > or = 1 x 10(-5) M induce adverse effects on morphology and contractile activity of postnatal myocardial cell cultures. PMID- 1288759 TI - Endpoints of spermatotoxicity in the rat after short duration exposures to fourteen reproductive toxicants. AB - Multiple endpoints of spermatotoxicity in short duration tests (1-5 days exposure; 2.5-week assay interval) were investigated in a number of chemicals reported to produce minimal to severe reproductive effects when administered subchronically. Six of these chemicals (boric acid, dinoseb, 2,5-hexanedione, methoxychlor, metronidazole, ornidazole) produced substantial spermatotoxicity after 1 to 5 doses. Spermatotoxic effects of chlordimeform were equivocal while p,p'-DDT, n-hexane, and sodium chlorite were judged negative. Four chemicals with known acute effects (benomyl, busulfan, ethylene glycol monomethyl ether, nitrobenzene) elicited expected histopathologic responses after a single dose. Testicular histology, testicular sperm head counts, cauda sperm counts, sperm morphology, and sperm velocity proved to be the most toxicologically sensitive endpoints in one or more of the studies, but histopathology of the testis and epididymis was the most consistent indicator of reproductive damage. The percentage of motile sperm and sperm concentration in the epididymal fluid were the least sensitive measurements. The data suggested that most chemicals with the potential to produce moderate to severe sperm damage are detectable with a short duration test. Complementary multiple endpoints enhanced the interpretation of results, often identified cellular targets, and provided insight on possible mechanisms. Specific responses were often similar to specific effects reported for subchronic exposures. A short duration test could be of value as a screen in structure-activity studies or to set priorities for chemicals requiring further evaluation. As a supplement to breeding studies, the data generated in the short test could also be used to enhance the design and interpretation of the longer tests. PMID- 1288760 TI - Effects of three male reproductive toxicants on rat cauda epididymal sperm motion. AB - The sensitivity of the CellSoft computer-assisted sperm analysis (CASA) system to detect changes in rat sperm motion was evaluated. CASA motion endpoints were measured in cauda epididymal sperm from Long-Evans rats treated with each of three known male reproductive toxicants reported to affect the epididymis and epididymal sperm motility: alpha-chlorohydrin, ornidazole, and trimethylphosphate. Significant changes in endpoints describing sperm swimming vigor (curvilinear velocity and straight-line velocity) and pattern (linearity and amplitude of lateral head displacement) were observed for rats dosed with each agent when evaluations included mean values and other statistical parameters (i.e., percentiles and distributional shape). alpha-Chlorohydrin (ACH) treatment (10 mg/kg/day; 8 days) resulted in reductions in the mean percentage of motile sperm, curvilinear velocity (VCL), straight-line velocity (VSL), lateral head displacement (ALH), and linearity (LIN). Treatment with ornidazole (ONZ) (200 mg/kg/day/14 days) reduced the percentage of motile sperm. Mean VCL, VSL, and ALH were reduced by 400 mg ONZ/kg/day treatment. Trimethylphosphate (TMP) treatment led to (a) a reduction in the 75th and 90th percentiles for ALH (100 mg TMP/kg/day; 5 days) (P < or = 0.04), (b) a reduction in VCL, VSL, and ALH (250 mg TMP/kg/day), (c) a reduction in the percentage of motile cells and in the 10th and 25th percentiles for VSL (600 mg TMP/kg/day), and (d) increases in the 90th percentile for VSL, in the mean, 75th, and 90th percentiles for VCL, and in the 75th and 90th percentiles for ALH (600 mg TMP/kg/day). The general utility of these analytic approaches in reproductive toxicology studies was demonstrated in the observations of effects at or below dose levels previously reported. PMID- 1288761 TI - Fertility and semen quality of workers exposed to high temperatures in the ceramics industry. AB - The objective of this study was to test the hypothesis that chronic occupational exposure to high temperatures may be detrimental to male reproduction. The study was based on 92 healthy ceramics oven operators with a long exposure to high temperatures, and 87 controls, recruited from the shipment department of the same industry. Interviews with all subjects provided data on sociodemographic characteristics, health status, and fertility problems. Semen analysis was carried out on 46 of the workers exposed to high temperatures, and 14 of the controls, and included evaluation of the sperm concentration, morphology, and motility, including computer-assisted sperm motion analysis (velocity, linearity, ALH, BCF). The results of the questionnaire showed that exposed individuals had a higher incidence of childlessness and of self-reported difficulty in conceiving than controls. The semen analysis showed no significant differences except in sperm velocity. Although differences in semen parameters, taken singly, were not statistically significant, the overall evaluation of the sperm parameters indicated a higher prevalence of pathologic sperm profiles among the exposed compared to the controls. PMID- 1288762 TI - Caffeine-mediated effects on reproductive health over two generations in rats. AB - The present study was designed to investigate the mechanism(s) underlying previously observed birth weight differences found in the first litter of the second (F2) generation bred from caffeine-exposed F1 females. The effect of exposure to caffeine in utero on subsequent sexual receptivity, fertility, gestation length, parturition, nesting activity, maternal behaviour, and reproductive senescence in the F1 mothers, and the viability of the F2 offspring was investigated. This information was collected by breeding control or caffeine exposed females for 8 consecutive litters. It was demonstrated that exposure to caffeine did not affect the sexual receptivity, fertility, gestation length, or maternal behaviour of the F1 females, but parturition was prolonged and the viability of the F2 generation was seriously jeopardized. Many F2 pups were born significantly larger than their control counterparts and a significant proportion of litters (after the first two litters) were wholly stillborn. It was concluded that a changed genetic program, mediated via the F2 fetus, delayed the normal progression of parturition. This, in turn, compromised the F1 mothers and caused increased mortality of their offspring. The severity of the outcome was dose dependent. PMID- 1288763 TI - Susceptibility to teratogenicity of hypervitaminosis-A in X-monosomy mice. AB - We previously showed that the incidence of external malformations induced by biotin deficiency did not differ either between XO and XX dams or between XO and XX fetuses. To clarify whether this phenomenon is specific to biotin deficiency or more generally associated with other teratogens, we examined whether XO mice are more susceptible to teratogenic effects of hypervitaminosis-A. Pregnant XO and XX mice were given an excessive vitamin A diets (1.0 to 1.5 x 10(6) IU/kg) from days 0 to 17 of gestation. Maternal hypervitaminosis-A produced a high incidence of external malformations (65 to 80%), skeletal anomalies (33 to 47%), and variations (99 to 100%) in the fetuses. However, there is no difference in their incidences between XO and XX dams or between XO and XX fetuses. Together with previous findings, this suggests that developmental stability of the mouse embryo is not affected by missing of one whole X chromosome even with exposure to teratogens. PMID- 1288764 TI - [Measurement errors in determination of electrolyte concentrations with ion selective electrodes in the presence of inorganic or metabolizable anions]. AB - Ion-selective electrodes (ISE) from various manufacturers were tested with regard to their accuracy in determining the concentrations of sodium, potassium and calcium in aqueous solutions when uni- or polyvalent, inorganic or organic anions are being present in physiological concentrations. The results obtained by all measuring instruments using ISE revealed that the presence of anions such as acetate, citrate, malate, lactate, phosphate or sulfate, either in physiological or therapeutic concentrations, may lead to considerable errors when determining the concentrations of sodium and calcium. A certain caution is therefore recommended in order to minimize the risk when using ISE for the electrolyte diagnosis of infusion solutions, blood derivatives, dialysates and urine samples. PMID- 1288765 TI - Superiority of gel centrifugation in antibody screening and identification. AB - We report on the direct comparison of gel centrifugation technique and tube testing for antibody screening (ABS) under controlled routine conditions. 3,000 blood samples were screened for antibodies (AB) by gel centrifugation (ID-System, bromelin 37 degrees C and room temperature, indirect antiglobulin test with LISS) and a sensitive tube test (TT; bromelin two-phase test, 37 degrees C and room temperature, and indirect antiglobulin test with 22% bovine albumin) in parallel. By ID significantly more relevant and potentially hemolytic AB (51 vs. 35 AB/1.7 vs. 1.2%) could be detected: anti-E 4, -C 1, -D 4, -CW 2, -c 2, -Jk(a) 2, -Jk(b) 1. Eleven of these even remained negative in TT when retested with increased sensitivity and taking additional (homozygous) test cells. In addition, naturally occurring but rarely hemolytic AB (35 vs. 23 AB/1.2 vs. 0.8%) were more frequently detectable by ID: anti-Le(a) 6, -Le(b) 2, -P1 6. In contrast, only two AB were only positive in TT: anti-Le(a) 1, -Le(a, b) 1. The main disadvantage of the ID was its frequent positivity (7.7 vs. 4.3%) due to irrelevant cold AB (anti I, -HI, -H) and unspecific factors. This can be partly reduced by omission of the bromelin test at room temperature (ID 3.0%, TT 1.5%) as the detection of relevant AB is not affected. The frequency of naturally occurring AB was still the same as in TT (0.7%) when bromelin at room temperature was omitted in both techniques. Further advantages of the ID are simplicity, small volumes of sera and reagents, and easy evaluation. PMID- 1288766 TI - [Effect of various plasma preparations and i.v. immunoglobulins on the function of lymphocytes and monocytes in vitro]. AB - Transfusion of whole blood or blood components has an immunosuppressive effect on the recipient and induces changes of several immunological parameters. Especially blood plasma or plasma components were suspected to show an immunosuppressive action. We therefore studied in vitro the effects of autologous and homologous fresh frozen plasma (FFP), fresh plasma (FP) and heparin plasma (HP) as well as the influence of different commercial i.v. immunoglobulins (IVIG) on the mixed lymphocyte reaction (MLR), the mitogen-induced lymphocyte transformation and the inhibition of phagocytosis of red blood cells, measured in the monocyte-monolayer assay (MMA). We demonstrate that autologous and homologous plasma inhibit the PHA and ConA response of lymphocytes (p < 0.025). Minimal differences between homo- and autologous plasma were only observed for FP in PHA-induced lymphocytes. IVIG reduced, in a dose-dependent manner, the MLR and PHA response to basal values. In contrast, plasma and IVIG showed only small effects on the PWM response rates. The addition of FFP, FP, HP or IVIG to cultured monocytes resulted in a significant inhibition of red blood cell phagocytosis, ranging from 76 to 87%. We conclude from our study that, besides unspecific mechanisms, an unknown plasma factor which is enriched in the immunoglobulin fraction of plasma is able to suppress the T-cell immune response. PMID- 1288767 TI - Anticoagulation-dependent inhibition of in vitro complement activation by anti apo-B sepharose 4B CL. AB - During LDL apheresis, various combinations of heparin and citrate are used for anticoagulation. With an in vitro batch system we examined whether heparin/citrate combinations can be optimized in terms of complement activation inhibition without the loss of anticoagulant potency. Plasma anticoagulated by using six clinically applicable regimens was incubated with anti-apo-B antibody coupled Sepharose 4B CL, and the anaphylatoxin content of the supernatant was investigated. A significant dose-dependent reduction of complement activation was achieved by anticoagulating whole blood with 10 U/ml heparin (p < 0.05) if compared with serum whereas citrate inhibited more effectively the generation of C5a (desarg) even at a low concentration (ACD-B 1:20) (p < 0.01). The lowest anaphylatoxin level was generated when heparin (10 U/ml) plus citrate (ACD-B 1:10) were applied, although such an approach may be of limited clinical interest. The empirically chosen heparin plus citrate ratio (2 U/ml, 1:20, respectively) provides for an optimal and almost ideal inhibition of complement activation and contributes considerably to the good tolerability of the immunoadsorbent. PMID- 1288768 TI - Effects of leukocyte depletion on the formation of anaphylatoxins in stored whole blood. AB - As reported earlier, factors of the complement cascade get activated in CPD-A1 stabilized whole blood. As early as after 10 days of storage under normal blood bank conditions the elevations of the concentrations of C3a-desArg and C4a-des Arg were highly significant. By contrast, the concentration of the C3 activator complex C4b2b remained unchanged even after 3 weeks of storage. Leukocyte depletion partially inhibited the activation of C4 but had no effect on C3a concentrations. Therefore, cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even through the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities such as activation of platelets which may lead to hypercoagulability and thrombosis. PMID- 1288770 TI - Platelet apheresis with Vivacell BT798 DEA, haemonetics V-50 and PCS-Plus: preparation efficiency and product quality using identical donors. AB - Different platelet apheresis techniques were used for preparing platelet concentrates: the continuous flow method with Vivacell BT 798 DEA, the discontinuous flow method with V-50 of Haemonetics, and their plasmapheresis device PCS-Plus. 20 of our donors underwent all three procedures. All platelet separations led to suitable platelet concentrates of 3 x 10(11) platelets within less than 90 min. However, the contaminating leukocytes reached 2 x 10(8). Due to less intense citrate reactions and a shorter donation time the donor acceptance of the continuous flow method was higher as compared with the discontinuous flow method. PMID- 1288769 TI - Anaphylatoxin generation and distribution during in vitro LDL apheresis. AB - The extent of anti-apo-B IgG-Sepharose-induced complement activation in serum and plasma (heparin 2 U/ml and ACD-B 1:20) was investigated using an in vitro model of LDL apheresis. The total volume of serum or plasma loaded to the chromatography column was collected in defined aliquots. The washing, desorption and regeneration fluids were processed in the same way. From the obtained values of generated complement split products C3a (desarg), C4a (desarg), C5a (desarg) and complement proteins C3, C4, C5, the conversion rates of the precursor were calculated. In the experiments with serum, 19% of C3, 8% of C4 and 2.3% of C5 were converted by the immunoadsorbent, whereas with plasma 7, 6, and 0.6%, respectively, were found. Furthermore, only 60-74% of total anaphylatoxins were found in the effluent during the loading process. The residual 26-40% was removed from the column with the subsequent washing fluids. Therefore, in the clinical routine, only a reduced part of generated anaphylatoxins will be retransfused to the patient. The fact that C5 is converted to the most limited extent to its biologically active fragment additionally contributes to the understanding of the good clinical tolerability of the LDL apheresis. PMID- 1288771 TI - Evaluation of the Haemonetics V50--time saver protocol. AB - 196 platelet apheresis procedures using the cell separator Haemonetics V 50 were performed applying 8 cycles under varying conditions. The anticoagulant ACD-A was used in a whole-blood to anticoagulant ratio of 8:1. The flow rate was selected for a range of 40-70 ml/min and the centrifuge speed was established at 4,800 and 4,400 rpm. The PWC factor was chosen between 0 and 4. 162 procedures could be statistically evaluated. 34 apheresis were accompanied with technical complications. The mean yield was (4.3 +/- 1.05) x 10(11) platelets, and the average of extraction efficiency (EE) was 53.9 +/- 8.2%. An analysis of variance confirmed that a higher flow rate decreased the EE (p < 0.002) and also the leukocyte counts (p < 0.0005). Increasing the PWC factor led to a higher EE; however, the leukocyte counts of the platelet concentrate were also increased (p < 0.0005). The g force has an essential effect. A high g force of the centrifuge permits to obtain a large quantity of platelets which is combined with a higher leukocyte contamination. Decreasing the centrifuge speed to 4,400 rpm by using PWC factors of 0 and 4 with different flow rates (50 and 60 ml/min) decreased the EE and the leukocyte counts in the product. PMID- 1288772 TI - [International standardization of product codes]. PMID- 1288773 TI - Product directory. PMID- 1288775 TI - [Laparoscopy-assisted vaginal hysterectomy: initial experiences with an extrafascial technique]. AB - This is a report on 4 cases of vaginal hysterectomy assisted by laparoscopy. The indications were dysfunctional hemorrhages, uterus myomatosus as well as 1 case of cervical intraepithelial neoplasia. Postoperatively, no complications were observed. It can therefore be concluded that with laparoscopic assistance the technical spectrum of hysterectomy can be enlarged. The disadvantage, if one can refer to it as such, implies the necessity of the gynecologist being a well trained laparoscopist. PMID- 1288774 TI - [Immunologic factors in habitual abortion]. AB - Recent advances in immunology have discovered two immunological factors in part of the patients with habitual first-trimester abortions. Antibody formation against the major histocompatibility antigens (HLA = human leukocyte antigen) which can be demonstrated during normal pregnancy is often not detectable in these patients, sometimes presumably because of compatibility in the HLA antigens between mother and fetus. In a high percentage of these patients immunotherapy by subcutaneous leukocyte injections can lead to antibody formation and successful pregnancy. As another immunological factor, a genetic variant of the complement inactivating leukocyte differentiation antigen CD46 (= TLX antigen, = membrane cofactor protein) could be identified, which can be seen more frequently in patients with habitual abortions as compared to healthy controls. Both factors seem just to contribute to a predisposition for early-pregnancy abortions rather than to be an absolute barrier, as they can also be seen in normal pregnancy and successful carriages can also occur without any therapy in early-pregnancy aborters with an immunological background. PMID- 1288776 TI - [Effect of high performance sports on female menstrual cycle exemplified by windsurfing]. AB - Questionnaires were sent to all female members (n = 60) of the Austrian Funboard Association (funboard = the most athletic windsurfing class). They included questions about the menstrual cycle, physical capacity, libido and performance dependent on the particular cycle phase. There was no significant libido or capacity peak, neither for the windsurfers nor for a normal collective (n = 100); on the other hand there was an evident low during menstruation. A mean length of the menstrual cycle of 26.5 +/- 2.8 days and a bleeding time of 4.4 +/- 1.2 days were found, while metrorrhaghia and dysmenorrhea were less frequent than in the normal collective. One reason for these findings could be that physical activity reduces dysmenorrhea. PMID- 1288777 TI - Clinical assessment of fetal blood flow velocimetry. AB - A statistical procedure is presented to analyze the relation between Doppler indices (DIs) such as pulsatility index (PI), resistance index (RI), A/B and clinical data of pregnancy and fetal outcome of three groups: (1) uncomplicated pregnancy, eutrophic fetus (NF), (2) pregnancy-induced hypertension (PIH), and (3) pregnancy and delivery of a dystrophic fetus (IUGR), and the acidity classes according to Saling, respectively. Proceeding and mathematical requirements as well as the possibilities to validate the methodology are introduced, and an application to previously published data is presented. By multivariate analysis of the data a fair prognosis of NF, PIH and IUGR was possible. The variability inherent to the data sampling requires a mathematical postprocessing in the framework of an adequate model before any clinical conclusions can be derived from DIs. PMID- 1288778 TI - [Lung hypoplasia as a complication of prolonged, premature rupture of fetal membranes in the 24th week of pregnancy]. AB - We examined 4 gravidae with rupture of membranes before the 24th week of gestation. In contrast to pathophysiological models we observed fetal respiratory movements and a reduced amount of amniotic fluid in all patients. PMID- 1288779 TI - [Assessing the status of obstetrics and gynecology. Thoughts and reflections on the world congress in Singapore]. PMID- 1288780 TI - [Laparoscopic surgical therapy of tubal pregnancy]. PMID- 1288781 TI - [Conservative laparoscopic therapy of tubal pregnancy]. PMID- 1288782 TI - [Laparoscopic operations of neoplastic changes of the ovary]. PMID- 1288783 TI - [Surgical hysteroscopy]. PMID- 1288784 TI - [7th Workshop on Multiple Pregnancy. Berlin-Charlottenburg, 30 May to 1 June 1991]. PMID- 1288786 TI - Required: competence assessment and credentialing. PMID- 1288785 TI - Applying Attila. PMID- 1288787 TI - Tuning in to learners' styles. PMID- 1288788 TI - Research questions for staff development educators. PMID- 1288789 TI - Prioritize your training requests. PMID- 1288790 TI - Four tips to increase program attendance. PMID- 1288791 TI - Six strategies for "enlightened" management. PMID- 1288793 TI - Break-even analysis: an essential tool for financial success. PMID- 1288792 TI - Proving that staff development makes the difference. PMID- 1288794 TI - Bone physiology and metabolism in dental implantology: risk factors for osteoporosis and other metabolic bone diseases. AB - Placing a dental implant elicits a time-dependent bone response controlled by wound-healing factors (cytokines, bioelectrical signals), biomechanics (gravitational, functional, and therapeutic loads), and mineral metabolism (hormones, diet, excretion). The osseous response to an implant involves four physiological stages: (1) endosteal and periosteal callus formation; (2) compaction and remodeling of the callus; (3) remodeling (turnover) of the nonvital interface and adjacent bone; and (4) maturation (secondary mineralization) of new bone. Long-term maintenance of a rigid implant interface is related to continual bone remodeling. Common metabolic bone disorders affecting potential implant patients are osteopenia ("osteoporosis"), renal osteodystrophy, osteomalacia, and Paget's disease. The most prevalent problem is a long-term negative calcium balance leading to a compromise in bone strength. Symptomatic osteoporosis (usually wrist, hip, and/or spine fractures) affects 4 to 50 percent of the population depending on age, race, sex, endocrine status, and life-style. Postmenopausal white and Asian females present the greatest risk. The jaws of "osteoporotic" adults are variably affected because of the moderating influence of mechanical function. Management of metabolic bone disorders is an important consideration in diagnosis, treatment planning, and long-term monitoring of dental implants. Bone metabolic counseling, a natural extension of preventative dentistry, is an unexpected benefit readily appreciated by patients and their families. PMID- 1288795 TI - How to treat ailing and failing implants. AB - This article describes treatment of the ailing implant (bone loss with pocketing but static at the maintenance checks) and the failing implant (bone loss with pocketing, bleeding upon probing, purulence, and evidence of continuing bone loss irrespective of therapy). Because the surface of the implant is contaminated with endotoxin, it must be detoxified before any regenerative therapy. Studies have shown that citric acid is effective in detoxifying the hydroxyapatite-coated surfaces while tetracycline is more effective in sterilizing the metallic substrate fixtures. Guided tissue regeneration is useful as a "barrier" to prevent exfoliation of the grafted material. Both nonresorbable and resorbable materials have been used with great success. Allografts (freeze-dried bone) and alloplasts (synthetic materials) may be used to achieve a sulcus of decreased depth and possibly some type of osseous regeneration. The author recommends the use of the allograft if the surface is completely detoxified and the alloplast if it is not certain that the surface is sterilized and free of endotoxin. The allograft, being resorbable, will not effect biologic healing against a contaminated surface; hence, the use of the alloplast to "fill" the defect and prevent epithelial invagination. PMID- 1288796 TI - Retrieval analyses of a blade implant after 231 months of clinical function. AB - A blade implant that was retrieved in 1990 after 231 months of clinical function (since 1971) was analyzed with respect to clinical, histological, and biomechanical characteristics. The implant clinical records demonstrated no abnormalities or pathological lesions over the tenure of treatment. The bone to implant interface showed a mixture of interfacial tissue components and conditions with adequate direct bone contact (46.4 to 82.3 percent) for classification as osseointegrated. The abutment fracture leading to removal was characterized as a cyclic fatigue mechanism and the distribution of tissue components along the interface could not be correlated with specific biomechanical loading directions. This report considers the clinical and biomechanical records as they relate to the detailed histological investigation. PMID- 1288797 TI - The influence of implant design, application, and site on clinical performance and crestal bone: a multicenter, multidisciplinary clinical study. Dental Implant Clinical Research Group (Planning Committee). AB - This investigation is designed to provide scientific data that is directly relevant to the placement of dental implants. The study is concerned with the influence of implant design, application, and location on long-term clinical performance and crestal bone response over 5 years of function. It involves approximately 700 patients at 30 Veterans Administration Medical Centers from various geographic regions. Patients are being entered into the study over an 18 month period and monitored (post-loading) over 5 years. The participating centers were randomly assigned to one of two separate, independent study groups. Complications and adverse responses associated with the placement and use of the implants will be evaluated and all failures thoroughly documented. The experimental design and sample size are based on the primary hypothesis that an implant-supported prosthesis will be successful/functional over a 5-year period in at least 90 percent of the cases treated. Secondary hypotheses to be tested are (1) the success rate among implant designs are the same over a 5-year period; (2) the success rate among implant applications are the same over a 5-year period; (3) the success rate of individual implants are the same with regard to jaw location over a 5-year period; (4) the loss of crestal bone at the individual implant sites are the same among the implant designs over a 5-year period; and (5) the complications and adverse responses experienced with the different implant designs are the same over a 5-year period. The experimental design of this multicenter, multidisciplinary, randomized investigation is a cooperative effort of the Department of Veterans Affairs and several United States dental schools. PMID- 1288798 TI - Antibacterial activity of dental implant metals. AB - This study was conducted to investigate the specific in vitro antibacterial effect of seven dental implant metals on oral bacteria which have often been identified in failing implants. The metals chosen for evaluation were titanium, chromium, cobalt, aluminum, iron, gold, and vanadium. These metals were selected because they are contained in many commonly used dental implants. The bacteria selected for this study included isolates of Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaniogenica, Actinobacillus actinomycetemcomitans, Actinomyces naeslundii, and Actinomyces viscosus. Sets of tubes containing either supplemented trypticase soy broth, brain-heart infusion-yeast extract, or brain-heart infusion-yeast extract with 5 percent defibrinated rabbit blood were aseptically prepared with doubling dilutions of the seven metals starting at an initial concentration of 500 micrograms/ml and terminating at 0 microgram/ml. Cultures of each organism were inoculated into each set of broth tubes containing all concentrations of metals. Tubes were incubated either anaerobically or in an atmosphere of 5 percent carbon dioxide for 48 hours at 35 degrees C and then assayed for ATP content which was proportional to the viable cellular biomass. The results showed that, although being bacteria and concentration dependent, all seven metals suppressed the growth of each organism. The rank order of antibacterial activity expressed by dental implant metals was gold > titanium > cobalt > vanadium > aluminum > chromium > iron. PMID- 1288799 TI - Tissue-supported implant overdentures. AB - Overdenture techniques can be modified for use with implants. Generally the implants, which replace the tooth roots, can be placed in a position to permit optimum retention and stability as well as enhancing esthetics. Bony undercuts, which at times are present with the retention of tooth roots, are not a problem when using implants. Various retentive schemes are available to retain the prosthesis and can be matched to the individual needs of patients in regard to retention, stability, and the ability to insert and remove prostheses. Two implants can adequately support an overdenture. The superstructure must be designed to enable the patient to maintain a healthy oral environment. The patient must understand and be able to perform required oral hygiene procedures. The use of overdentures over implants affords the dentist another option in meeting the needs of the patients. PMID- 1288800 TI - Estimating the validity of radiographic measurements of marginal bone height changes around osseointegrated implants. AB - The accuracy of determining marginal bone height changes around osseointegrated implants depends on the validity of comparing serial films and the reliability of the measurements. X-ray beam orientation changes can alter the validity of serial films. A human dry mandible containing a Branemark implant was irradiated +/- 12 degrees in the vertical plane at 1-degree intervals to the perpendicular to the long axis of the fixture. The thread width was recorded on both sides of each fixture image using a computer. Twenty-five randomized unclassified images were remeasured and the vertical angle of the x-ray beam was estimated from the previous measurements to test for validity of comparing images. The reliability of measurements with altered image magnification and penumbra were calculated. The reliability of 24 repeated thread width measurements was a SD of 0.01 mm. Of the 25 unknown beam angulations, 32 percent matched correctly, 20 percent +/- 1 degree, 16 percent +/- 2 degrees, or 68 percent < or = +/- 2 degrees. Alteration from a short to a long cone technique was estimated to produce magnification errors similar to the reliability SD of 0.01 mm. Similarly the penumbra varied from 0.057 mm to 0.032 mm with short to long cones using a 1.0-mm focal spot. With a 0.6-mm focal spot, the smallest penumbra of 0.19 mm was twice the measurement reliability. This method demonstrated x-ray beam angulation and validity for comparing serial films can be estimated for the extreme variations but not accurately for +9 to -6 degrees from a tangent to the fixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288801 TI - Early detection of osseointegration using scanning electron microscopy and the interfacial biopsy chamber: a pilot study. AB - This pilot project attempted to demonstrate microscopic evidence of osseointegration in a controlled environment as originally presented by Branemark. The Interfacial Biopsy Chamber was developed to collect titanium/tissue serial biopsies of the implant-tissue interface at various stages of wound healing. It was surgically placed in two Flemish giant rabbits and titanium/tissue biopsies were collected at 35 and 70 days. The biopsies were examined using scanning electron microscopy (x2000, x3200, and x7500) and light microscopy (x230). Osseous tissue was found in intimate contact with the titanium implant surface with no evidence of an intervening fibrous layer. Cells with the morphological characteristics of osteoblasts were observed covering the titanium surface. Processes extending from the main body of these cells were in intimate contact with the titanium surface, following the machining striations. The photomicrographs were similar to those presented earlier by Branemark. The project also suggested the use of the Interfacial Biopsy Chamber as a research instrument for the collection of implant/tissue interface serial biopsy samples. PMID- 1288802 TI - Intraoral corrosion resulting from coupling dental implants and restorative metallic systems. AB - Materials used for the construction of dental restorations and implants include a wide range of metals and alloys, ceramics and carbons, and polymers. When metals and alloys are placed in direct contact in the oral cavity, a galvanic cell can be formed that may compromise the longevity of one or more of the materials in the couple. In vitro electrochemical corrosion analyses have proven to be a valuable tool for providing guidance on the selection of metallic materials. These analyses can provide basic data on electrochemical potentials, current rates, and the evaluation of galvanic corrosion conditions. This article seeks to provide the clinician with information that can be valuable in the selection of metallic materials that may be placed in direct contact with one another in the oral cavity. PMID- 1288803 TI - Microscopy of bone cells, bone tissue, and bone healing around implants. AB - Newer methods of scanning microscopy using both light and electrons are particularly relevant to the study of bone cells, bone matrix organization, matrix mineralization, bone modeling and remodeling, and the adaptation of cells and matrix to implants. Most of such studies are conducted on retrieved implants, at least after the death of the related tissue. Because the retention of the tissue-implant relationship in such preserved tissue is crucial for critical evaluation of the implant, methods based on the study of flat surfaces of embedded tissue blocks are very important. Using electrons, the backscattered electrons in a scanning electron microscope can be employed to evaluate mean atomic number (density) and cathodoluminescence can identify polymers and fluorescent labels. Using light, confocal microscopical techniques permit the examination of layers deep to the block face. Confocal reflected and fluorescence methods allow the study of cell behavior upon both transparent and opaque substrates in the laboratory. Examples of the above are presented and interpretation problems discussed. Current experiments are aimed at enabling the study of bone wound healing and bone adaptation to implanted materials in vivo, through the implantation of optical quality windows and/or newly conceived and designed microscopical objective lenses. PMID- 1288804 TI - A surgical guide for insertion of implant fixtures. AB - Successful prosthodontic rehabilitation of edentulous ridges with implants is dependent upon the alignment of multiple fixtures. A simple technique for fabricating a surgical guide is presented in this article. PMID- 1288805 TI - Utilization of 3D/Dental software for precise implant site selection: clinical reports. AB - Preoperative planning is an essential aspect of endosteal implant placement. Three-dimensional imaging allows the surgeon and restorative dentist to accurately visualize potential implant receptor sites relative to adjacent vital structures. This information is correlated with the planned occlusion, and transferred to the patient by means of a surgical prosthetic guide, which is developed on the diagnostic cast. The steps involved in planning and placing implants in an atrophic mandible in the first case illustrates the value of three dimensional scanning in treating patients with limited bone volume. The second case presented with a mandibular bilateral distal extension partial denture, which was ultimately replaced with two implant-supported fixed prostheses. The use of three-dimensional imaging showed the location of the inferior alveolar neurovascular bundle which allowed utilization of all of the bone above it without encroaching on the nerve. The third case illustrates an edentulous maxilla where visualization of the osseous contour allowed for implant placement at an optimal angulation to provide support for the planned prosthesis. PMID- 1288806 TI - An evaluation of the Periotest system. Part I: Examiner reliability and repeatability of readings. Dental Implant Clinical Group (Planning Committee). AB - The clinical success of endosseous dental implants is related to the extent of osseointegration. Many of the presently used methods of evaluating osseointegration are highly subjective. The Periotest is claimed to offer a more objective means to assess osseointegration and supporting bone stability of implants by means of microcomputer-controlled percussion. Investigators involved in a clinical study on dental implants being conducted by the Dental Implant Clinical Research Group participated in a two-part in vitro evaluation of the Periotest system. The first part, with which this article is concerned, involved each of 35 investigators taking three readings for each of 16 models designed to simulate an implant in place in the oral cavity and to cover most of the effective measuring range of the instrument. The Periotest system generally demonstrated a high degree of reliability and repeatability, with higher variability associated with specific model samples. Further evaluation of the Periotest as a research instrument will be conducted within the clinical environment of the Dental Implant Clinical Research Group study. PMID- 1288807 TI - High lip line, gingival contouring, and single tooth implants: clinical report. PMID- 1288808 TI - Treatment of a resorbed maxilla with sinus grafting, implants, and spark erosion overdenture: clinical report. PMID- 1288809 TI - Detoxification of endotoxin-contaminated titanium and hydroxyapatite-coated surfaces utilizing various chemotherapeutic and mechanical modalities. AB - The surgical repair of the ailing implant may be complicated by the surface effects of pathogenic bacteria and their products. This study evaluated the ability of various chemotherapeutic modalities to detoxify endotoxin-contaminated titanium alloy and hydroxyapatite-coated test strips. Grit-blasted titanium alloy and hydroxyapatite-coated test strips were contaminated with purified outer membranes of Escherichia coli labeled with radioactive 14C. The titanium alloy strips were treated with citric acid, stannous fluoride, tetracycline HCl, chlorhexidine gluconate, hydrogen peroxide, chloramine T, sterile water, a plastic sonic scaler tip, and an air-powder abrasive unit. Hydroxyapatite-coated strips were treated with chloramine T, citric acid, or burnished with sterile water on cotton pellets. Residual lipopolysaccharide levels were measured by liquid scintillation spectrometry. The air-powder abrasive unit removed significantly greater amounts of lipopolysaccharide than all other treatment modalities on titanium samples (P < 0.05). A 60-second burnish with sterile water was able to remove significant amounts of lipopolysaccharide when compared with untreated controls (P < 0.05). Citric acid was superior in the removal of lipopolysaccharide from hydroxyapatite-coated surfaces when compared with the controls or chloramine T (P < 0.01). Detoxification of an implant infected surface may be beneficial when surgical repair of the ailing implant is indicated. PMID- 1288810 TI - Current status of tissue expanders in alveolar ridge augmentation: a review. AB - The need for major surgery involving bone and skin grafting procedures in the treatment of severe alveolar atrophy has, for many patients, been obviated by the advent of reliable endosseous implant systems. However, some patients, usually for medical, psychological, or financial reasons are unsuitable for endosseous implant therapy. In such patients, ridge augmentation with particulate hydroxyapatite may result in significantly improved denture function. However, hydroxyapatite tends to disseminate throughout any surgically created subperiosteal space, resulting in an undesirable ridge form. This problem may be overcome by the use of tissue expanders in a two-stage surgical procedure. This article briefly reviews the concept of tissue expansion and describes its application to the technique of alveolar ridge augmentation. PMID- 1288811 TI - The surgical template: a prescription for implant success. AB - The surgical template is utilized in the planning and execution of a successful implant rehabilitation. A method of template fabrication is presented which is useful for cases requiring precise root form fixture placement. Stents are fabricated using a duplicate denture or acrylic base and orthodontic wire, which is contoured to create the acceptable perimetric limits of fixture placement. This approach provides good visual access, operator flexibility, and template stability. The technique can be utilized for the edentulous and the partially edentulous arch. PMID- 1288812 TI - Loss of ridge width and the single tooth implant: clinical report. PMID- 1288813 TI - Fibroblastic growth and attachment on hydroxyapatite-coated titanium surfaces following the use of various detoxification modalities. Part I: Noncontaminated hydroxyapatite. AB - Hydroxyapatite-coated titanium alloy test strips were treated with chlorhexidine gluconate, stannous fluoride, citric acid, tetracycline HCl, polymyxin B, hydrogen peroxide, and a plastic Cavitron tip: untreated sterile strips served as controls. The strips were incubated with cultured human gingival and periodontal ligament fibroblasts. Image analysis of three photomicrographs of each test strip (original magnification x350) indicated that the tetracycline HCl treatment resulted in significantly greater cellular surface area coverage compared with the other treatments. Citric acid and the plastic Cavitron tip also stimulated cell attachment, although the results from the Cavitron tip were not significantly different from citric acid or the other treatment groups. The remainder of the modalities and the untreated cellular controls experienced similar cellular coverage. PMID- 1288814 TI - Fibroblastic growth and attachment on hydroxyapatite-coated titanium surfaces following the use of various detoxification modalities. Part II: Contaminated hydroxyapatite. AB - This study evaluated the ability of various chemotherapeutic and mechanical modalities to detoxify endotoxin-contaminated hydroxyapatite-coated dental implant surfaces as determined by the early attachment and growth of human gingival fibroblasts. Hydroxyapatite-coated test strips were contaminated with purified outer membranes of Escherichia coli and treated with citric acid, hydrogen peroxide, stannous fluoride, chlorhexidine gluconate, tetracycline HCl, polymyxin B, a plastic sonic scaler tip, or left untreated (contaminated and sterile controls). Human gingival fibroblasts were then seeded onto the test strips and incubated for 48 hours. The citric acid-treated strips showed greater cell growth than the other treatments. The plastic sonic scaler tip and the polymyxin B-treated samples exhibited greater cell coverage than the sterile control specimens. The use of citric acid and/or a modified plastic sonic scaler tip may be a valuable adjunct when surgical repair of an ailing hydroxyapatite coated dental implant is contemplated. PMID- 1288815 TI - Lingualized integration: tooth molds and an occlusal scheme for edentulous implant patients. AB - The interface of bone and soft tissue to dental implants has been extensively documented, while the influence of biomechanics and the occlusal interface continues to be overlooked. Yet that same occlusal interface may ultimately be the prime factor in the lifetime survival rate of dental implants. What is lacking, for the practitioner, is a clear concept of the occlusal rehabilitation which is required and appropriate for the totally edentulous implant patient. Lingualized integration represents an occlusal scheme using specific tooth molds designed to improve the likelihood of maximum intercuspation and an absence of deflective occlusal contacts, provide cusp height for selective occlusal reshaping, and achieve a natural and pleasing appearance. Factors in the articulation and arrangement of the posterior teeth to assure the attainment of the fundamental goals of comfort, function, and appearance in occlusal rehabilitation for edentulous implant patients are included. PMID- 1288816 TI - Finite element analysis of interface geometry effects on the crestal bone surrounding a dental implant. AB - Using a two-dimensional axisymmetric finite element analysis technique, different geometrical configurations of implants, abutments, and interfaces have been investigated to alter the stress distribution in the crestal bone region. The crestal bone region is of particular interest due to observations of progressive bone resorption (saucerization). The ability of a prosthetic restoration-implant construct to transfer an appropriate stress at this region will, by definition of Wolff's law (bone's response to strain) and principles of bone remodeling, help to maintain the integrity of the surrounding bone via force transfer. The two geometries investigated involved a traditional flat mating surface and a slanted (oblique) mating surface. In both models a vertical load of 400 N (63 N/rad across 2 pi radians) was applied to the abutment apex. In the crestal bone region the oblique mating surface increased the transfer of horizontal stress 67 percent over the traditional flat mating surface design. The magnitude of stress transferred and the area which it was transferred across was increased in this region. Results indicate potentially more favorable mechanical conditions for bone maintenance surrounding an endosseous dental implant may be achieved if force is transferred preferentially via circumferential grooves and an oblique (dished) implant-abutment mating surface. These theoretical results are consistent with basic principles of stress transfer, stress shielding, and remodeling as well as clinical observations of bone maintenance and resorption. PMID- 1288817 TI - An evaluation of the Periotest system. Part II: Reliability and repeatability of instruments. Dental Implant Clinical Research Group (Planning Committee). AB - Investigators involved in a clinical study on dental implants being conducted by the Dental Implant Clinical Research Group participated in a two-part in vitro evaluation of the Periotest system. The first part involved each of 35 investigators taking three readings for each of 16 models designed to simulate an implant in place in the oral cavity and to cover most of the effective measuring range of the instrument. The second part, with which this article is concerned, was conducted by three study investigators to determine the level of agreement in readings for six different Periotest instruments. Readings were taken according to the manufacturer's instructions until two coincident readings were obtained. The readings were compared to evaluate inter- and intrainstrument reliability. Instrument repeatability was evaluated by examining the number of attempts required to obtain the two coincident readings. The Periotest system generally demonstrated a high degree of repeatability and reliability, with higher variability associated with specific model samples. PMID- 1288818 TI - [Differentiation antigens of hematopoietic cells (CD system)]. AB - Monoclonal antibodies allowed recognition and identification of a series of hematopoietic cell membrane antigens expressed on plasma membranes of leukemia patients and on cells of healthy subjects. Monoclonal antibodies produced in different laboratories were clustered on the basis of their reactivity with normal and malignant hematopoietic cells into CD (cluster of differentiation) groups, with defined properties of recognized antigens (glycoprotein, phosphoprotein or glycolipid nature, molecular weight, isoelectric point, amino acid or carbohydrate sequence, etc.) and with functional characteristics of the corresponding antigen and its distribution on cells of the hematopoietic system. This "CD system" of human hematopoietic cell differentiation antigens was established in a series of international laboratory workshops (1982-1989). The present state of the CD classification system, as assessed after the IVth International Workshop on Hematopoietic Cell Differentiation Antigens (1988/89), in which more than 100 laboratories analyzed over 1,000 monoclonal antibodies, is described. An overview of the data concerning properties of monoclonal antibodies produced in the authors' laboratory (monoclonal antibodies series Bra-) is presented. PMID- 1288819 TI - [Embryotoxic effects of N-nitrosodimethylamine in mice]. AB - N-nitrosodimethylamine was administered intraperitoneally in the dose of 5.5 mg.kg-1 body eight to pregnant ICR mice on days 3, 5, 9, 12 of gestation. The administered dose caused a statistically significant increase of resorptions at each stage of pregnancy studied. The pregnancy rate of females treated at any stage of organogenesis studied was reduced, most markedly in mice treated on day 12 of gestation. No malformations or skeletal anomalies were observed. PMID- 1288820 TI - [Properties of skeletal muscle sarcoplasmic reticulum membranes prepared in the presence of dithiothreitol]. AB - The authors studied the effect of dithiothreitol (DTT), an agent modulating the redox state of SH-groups, on functional properties of sarcoplasmic reticulum membranes of skeletal muscle. DTT (5 mmol.l-1) exerted a protective effect not only on (Ca2 + Mg2)-ATPase activity but also on the activity of Ca2+ uptake by vesicles, while the most pronounced effect was recorded at low levels of ionized Ca2+. The presence of DTT in the isolation medium decreased also passive permeability of membranes for Ca2+. In the light of the results obtained, modulation of the redox state is recommended for each isolation of membranes designed for the study of ion transport. PMID- 1288821 TI - [Abnormal CT brain scan during acute lymphoblastic leukemia in children]. AB - The results of CT brain scans were evaluated in 96 children with acute lymphoblastic leukemia in different stages of the disease. Practically normal findings were recorded at establishing the diagnosis (17 children), with the exception of infiltration of the brain and meninges in one patient. Examinations performed after induction chemotherapy (31 children) revealed abnormal CT scans in 55% of the children concerning most frequently dilatation of the cerebrospinal fluid pathways and exhibiting less frequently hypodense foci in the white matter. At check-up examinations after 9 months (following prophylaxis of CNS leukemia) these deviations from the norm had disappeared in some patients, in others they persisted and in the rest of the patients they were found to be aggravated. Examinations carried out several years after treatment completion (40 patients) showed abnormal CR scans in 43% of the patients. These involved particularly derangements in the density of the white matter which were of leuko-dystrophic type and atrophic changes characterized by dilatation of the cerebrospinal fluid pathways. The recorded changes in the CT brain scans were more pronounced in patients with high-risk forms of leukemia and intensive prophylaxis of CNS leukemia. PMID- 1288822 TI - [Super Duo latex fixation test--an alternative diagnostic method for trichomoniasis?]. AB - The reliability of the new latex-agglutination test super duo for the detection of antigens of T.vaginalis and Candida, a prospective screening method for trichomoniasis, was verified. In a group of 27 women the microscopic and culture diagnosis of trichomoniasis was established in 22 patients and 21 of them were positive in the latex-agglutination test for T.vaginalis. The immunochemical examination was not positive in either of the five women with findings of negative cultivation for the parasite. The intensity of agglutination was in good correlation with the clinical signs of inflammation. In asymptomatic women the reaction was indistinct. Vaginal candidiasis was revealed by culture in two women, one of them was positive on the latex-agglutination test for Candida. One woman with negative cultivation finding for yeast microorganisms was positive in the immunochemical test. Examination of asymptomatic sexual partners of trichomoniasis patients would be necessary to evaluate the suitability of the set for T.vaginalis infection screening. PMID- 1288823 TI - [Female sterility after appendicitis in childhood]. AB - The aim of the study was to establish the rate of sterility in women who had been operated on in childhood for perforated and non-perforated appendicitis. The group with perforated appendicitis consisted of 58 women who had been operated on at the age of 3 to 15 years and at the time of the follow-up examination they were in the age range of 23 to 41 years. Of these women 51 were married and 49 of them had one to three children. Two women (3.9%) were sterile. One had been operated on in adulthood for tubo-ovarial abscess in the right and pyosalpinx in the left tube and the other one was treated for repeated adnexitis in adulthood. The group with non-perforated appendicitis consisted of 168 women who had been operated on at the age of 3 to 15 years and at the time of the follow-up examination they were in the age range of 23 to 40 years. Of these women 145 were married and 141 had one to four children. Four women (2.8%) with the history of noncomplicated appendicitis were sterile. Our retrospective study showed no statistically significant difference in the occurrence rate of sterility in women operated on in childhood for perforated and non-perforated appendicitis. PMID- 1288824 TI - [Prostaglandin E1 in the long-term treatment of erectile dysfunction]. AB - Intravenous injections of Prostaglandin E1 were administered to 65 men suffering from erectile dysfunction. Later on, 59 of them administered the substance to themselves. Our experience as well as literary data have confirmed the efficacy of prostaglandin E1 administered intracavernously in the therapy of different forms of impotence, including the so-called psychogenic form. Its advantage is that it metabolizes directly in the cavernous tissue. Virtually no significant systemic side reactions were recorded and neither priapism nor fibrosis of the corpora cavernosa were observed after long-term treatment. Prostaglandin E1, a product of Leciva Praha, was used within the clinical study of this preparation. PMID- 1288825 TI - [History of the Surgery Clinic at the Slovak University Medical School in Bratislava during the war years (1941-1945)]. AB - The aim of the present study was to contribute to a good and objective understanding of the development of the Department of Surgery of the Medical School in Bratislava over the war years of 1941-1945. After Prof. MUDr. Kostlivy had left Slovakia, his student, Prof. MUDr. Konstantin Carsky was appointed head of the Clinic of Surgery, as it was officially named. Already during the period of World War II, Prof. Carsky became a remarkable and reknown personality of the School of Medicine of the Slovak University in Bratislava. The first Slovak school of surgery developed under his guidance. On the basis of archival sources and documents, the paper presents statistical data concerning some aspects of the pedagogical activities of the Clinic of Surgery, its staffing, and the complicated process of competence growth, particularly appointments to the highest academic ranks. PMID- 1288826 TI - [The role of polymorphonuclear leukocytes in the development of gastric lesions induced by indomethacin and ethanol and the relation of vascular permeability]. AB - The relationship between a reduced number of polymorphonuclear leukocytes (PMN), activated PMN/NBT (+) PMN/, permeability of gastric vessels, and disposition for the development of gastric lesions was studied following administration of indomethacin or ethanol in rats. Decrease in the number of circulating neutrophils and in the number of NBT (+) PMN after 3- or 6-day administration of methotrexate was found to diminish the disposition for the development of gastric lesions. Six-day administration of pentoxifylline resulted in a decreased number of NBT (+) PMN and in a diminished disposition for gastric mucosa injury induced by indomethacin, yet failed to reduce the occurrence rate of lesions after ethanol administration. No direct relationship was established between changes in gastric vascular permeability and decreased disposition for the development of gastric lesions after administration of methotrexate or pentoxifylline. (Fig. 3, Ref. 30.) PMID- 1288827 TI - [Changes in myocardial sensitivity after sudden with withdrawal of calcium channel blockers]. AB - Our previous experiments have suggested that besides the receptor cont and/or sensitivity a decrease of intracellular calcium level significantly participates in the mechanism of beta-blocker withdrawal 'rebound' phenomenon. This suggestion initiated studies in which possible changes in myocardial responsibility to cardioactive drugs were investigated in the condition of withdrawal of treatment with calcium entry blockers. The results showed increased cardiotoxicity of ouabain, aconitine and CaCl2, as well as an increased response of the heart to isoprenaline 24 hours after sudden cessation of treatment with verapamil (2 mg.kg 1 x 12 hours-1), diltiazem (3 mg.kg-1 x 12 hours-1) and nifedipine (0.5 mg.kg-1 x 12 hours-1). These results support the hypothesis of a common mechanism of the withdrawal syndrome of beta-lytics and calcium antagonists involving changes in intra-cellular calcium level. (Tab. 2, Fig. 4, Ref. 33.). PMID- 1288828 TI - [Prenatal virus infections and orofacial clefts]. AB - A potential teratogenic activity of virus infections caused by the viruses of rubella, influenza, parotitis, hepatitis B, cytomegalovirus and the Epstein-Barr virus was investigated. Specific antibodies against these viruses were examined serologically in children with orofacial clefts and in their mothers and the results were compared with those obtained in control children and their mothers. Different micromethods were used in performing the examinations (ELISA, RIA, NIR, KFR, HIT). Evaluation of the results and their statistical processing supports the assumption that prenatal infection may have occurred in the series studied induced by the viruses of influenza, rubella, cytomegalovirus, and possibly also by the Epstein-Barr virus. No association with the viruses of parotitis and hepatitis B was established. (Tab. 5, Ref. 36.) PMID- 1288829 TI - [Lungs and their function in heart disease]. AB - Pulmonary manifestations of cardiac diseases are reviewed and the contribution of pulmonary function assessment in diagnosis, management and prognosis of these diseases is being emphasized. Inborn and acquired diseases of the heart exert pathological effects on pulmonary hemodynamics and later on also on lung structure, clinically manifested by pulmonary symptomatology and abnormalities in pulmonary function. The basic mechanisms of pulmonary function derangement include pulmonary congestion and hyperreactivity of the airways as a consequence of increased blood pressure or flow in the pulmovascular network (postcapillary or hyperkinetic pulmonary hypertension). The severity of the given cardiac disease determines also the condition of pulmonary function. Thus examinations of pulmonary function substantially contribute to the classification of the functional state and to optimal choices in therapeutic strategy. Appropriate surgical or medical therapeutic procedures can improve the hemodynamic conditions in the pulmonary vascular network. This, in turn, leads to partial regression of morphological changes in the pulmonary parenchyma and thus to gradual improvement of pulmonary function. (Tab. 4, Fig. 4, Ref. 62.) PMID- 1288830 TI - [Primary culture in chemically defined medium of human fetal mammary epithelial cells within reconstituted matrix]. AB - A serum-free primary culture system has been developed which allows for three dimensional growth and differentiation of normal human fetal mammary epithelial cells within an extracellular matrix preparation. Human fetal mammary epithelial cells were isolated from the mammary glands of human female fetuses, 17 to 39 weeks-old. The "organoids" were embedded within a reconstituted basement membrane matrix prepared from the Engelbreth-Holm-Swarm (EHS) sarcoma according to the method of Hahm and Ip. "Organoids" were grown in either serum-free medium or in medium with fetal calf serum (FCS). The "organoid" proliferated over a 2 to 3 weeks culture period and remained viable for 1 or 2 months within the basement membrane matrix in serum free medium. Several types of colonies were observed; including alveolar-like budding clusters obtained from cultures of mammary gland from fetuses of over 20 weeks age, units with ductule-like projections and stellate-type colonies. Cell proliferation was dependent on the culture medium (with FCS no proliferation was obtained) and on the substratum (without matrix, significantly less growth and development occurred). These types of colonies are obtained when a glandular differentiation of cells budding from the malpighian epithelium is observed. Light microscopic and transmission electron microscopic studies were undertaken at the time of culture. This unique system using normal fetal mammary epithelial cells thus provides a model in which the regulation of human mammary development can be investigated. PMID- 1288831 TI - [Mechanisms of cellular detoxication, nuclear aluminum concentration and hepatocyte protection after experimental overload in rats]. AB - A single injection of a massive dose of Al-gluconate (4 mg.kg-1) into the saphenous vein of the rat did not provoke any ultrastructural damage in the liver cells, from 2 min. to 8 days after the injection. Al hepatocytes overload appeared only in nuclei and not in nuclei and not in lysosomes, contrarily to chronic intoxications. Nuclear Al concentration concerned only a small fraction of the quantity injected; another part was sequestered by the macrophage system after precipitation in the blood as phosphates chemically transformed during their incorporation in lysosomes. This effective detoxication mechanism which functioned probably after a first absorption by the hepatocyte, was likely to depend upon the form of gluconate and would explain the resistance of liver cells. PMID- 1288832 TI - Lipoprotein(a) and fibrinolysis. PMID- 1288833 TI - The write stuff: the journalology of cardiology. PMID- 1288834 TI - CCS Research Achievement Award--1992. Variations on the theme of coronary artery disease. PMID- 1288835 TI - The natural history of asymptomatic complete heart block. A case series from the Manitoba Follow-up Study. AB - Long-standing asymptomatic complete heart block is unusual in adults. The natural history of this condition with advancing age is unknown. Four cases of complete heart block documented in patients for 23 to 48 years are reported. These men had no evidence of structural heart disease and functioned normally without symptoms for many years. Three of the four subsequently developed symptoms and required permanent pacemaker insertion. These cases illustrate the good prognosis of asymptomatic complete heart block, but raise the concern that with advancing age, intervention with pacing frequently is necessary. PMID- 1288836 TI - Isolated post exercise delayed ST depression as a sign of severe ischemia: the influence of percutaneous transluminal coronary angioplasty. AB - The clinical implications of isolated late recovery ST depression were tested in patients with scintigraphically defined ischemia (coronary artery disease [CAD], n = 18) compared with patients without ischemia (n = 25). Spontaneous (78.4 versus 12.0%, P < 0.008) and exercise-induced angina (44.4 versus 0%, P < 0.0001) were more frequently seen in patients with CAD. Histories of unstable angina (33.3%), prior myocardial infarction (27.8%), ST elevated angina (22.2%) and significant stenosis in the left anterior descending artery (17 of 18, 94.4%) were almost exclusively seen in the CAD group. There was no significant difference between the two groups in capacity for exercise, maximum deviation of ST level or TV2 amplitude. Balloon angioplasty abolished late recovery ST changes in 63.6% of CAD patients. These results suggest that isolated late recovery ST depression, when accompanied with typical chest pain, may be considered as an indicator of myocardial ischemia, but this phenomenon is difficult to distinguish electrocardiographically. PMID- 1288837 TI - Pulmonary veno-occlusive disease and the CREST variant of scleroderma. AB - Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension. The authors describe a 48-year-old female with the Calcinosis-Raynaud's phenomenon Esophageal dysmotility-Sclerodactyly-Telangiectasia (CREST) variant of scleroderma who developed acute pulmonary hypertension with pulmonary infiltrates and a normal pulmonary capillary wedge pressure. At post mortem examination typical changes of pulmonary veno-occlusive disease were found. Similarities between this and other cases in the literature suggest a possible association between the CREST variant of scleroderma and pulmonary veno-occlusive disease. PMID- 1288838 TI - Disappearance of Q waves following thrombolysis for acute myocardial infarction. AB - The development of Q waves on the surface electrocardiogram generally is considered indicative of myocardial infarction. Such Q waves are usually permanent, though may regress and disappear over months to years. Transient Q waves have been described during myocardial ischemia without evidence of infarction. More recently, Q waves have been noted to develop transiently during the acute phases of infarction, possibly representing stunned myocardium. In this case report, a patient with an evolving anterior myocardial infarction and new septal Q waves was treated with intravenous thrombolytic therapy. Three hours following treatment the patient was clinically improved, and the septal Q waves had been replaced by small but obvious R waves. Despite a large area of myocardium at risk of infarction on the initial electrocardiogram, the resultant infarction was enzymatically and echocardiographically small. Early Q waves in acutely evolving myocardial infarction may represent severely ischemic, rather than irreversibly damaged, myocardium which may still be salvaged with thrombolytic therapy. PMID- 1288839 TI - Acute effect of rapid ventricular pacing and volume loading on total vascular capacitance. AB - OBJECTIVE: Rapid right ventricular pacing (RRVP) at 250 beats/min plus a saline volume load produces acute heart failure manifested by a limited increase in cardiac output in response to the volume load and increased right atrial, pulmonary artery and capillary wedge pressures. The effects on vascular capacitance are unknown. DESIGN: Three groups of six anesthetized splenectomized dogs were subjected to RRVP alone at 250 beats/min for 40 mins volume loading alone with intravenous 0.9% sodium chloride 40 mL/kg over 10 mins or volume loading followed by RRVP for 15 mins. Vascular capacitance, unstressed volume and compliance were determined from pressure-volume curves using transient circulatory arrests induced by acetylcholine before and 40 mins after starting the interventions. RESULTS: Neither RRVP nor volume loading alone produced acute heart failure or altered total vascular compliance. Fifteen minutes of RRVP after the volume load induced heart failure, reduced compliance (3.4 +/- 0.5 to 2.5 +/- 0.3 mL/mmHg/kg, P < 0.05), increased central blood volume (7.7 +/- 0.7 to 10.6 +/ 0.5 mL/kg, P < 0.01) and reduced the unstressed vascular volume to 57 +/- 10 mL/kg, compared with 77 +/- 9 mL/kg (P < 0.01) after the volume load alone. Stressed blood volume was increased similarly with either volume loading alone (20.1 +/- 2.0 to 30.0 +/- 1.7 mL/kg, P < 0.01) or volume loading plus RRVP (23.5 +/- 3.8 to 30.2 +/- 4.9 mL/kg, P < 0.01). The reduction in unstressed volume rather than an increase in stressed volume was the major peripheral change associated with acute heart failure induced by volume loading plus RRVP. CONCLUSION: RRVP reduced vascular capacitance by a reduction in unstressed volume. Acute volume loading of this smaller vascular compartment resulted in redistribution centrally and acute heart failure. PMID- 1288840 TI - Angiotensin-converting inhibitor enzymes: after the acronyms. PMID- 1288841 TI - Segregation of altered parental properties in fusions between Saccharomyces cerevisiae and the D-xylose fermenting yeasts Candida shehatae and Pichia stipitis. AB - A prototrophic strain of Saccharomyces cerevisiae CSIR Y190 MATa xyl-, resistant to high levels of ethanol, was hybridized with xylose-fermenting, auxotrophic mutants of Candida shehatae and Pichia stipitis through polyethylene glycol induced protoplast fusion in an attempt to produce ethanol-tolerant, xylose fermenting hybrids. Mononucleate fusants were obtained, but these dissociated into a mixture of parental-type segregants. Purified Candida- and Pichia resembling segregants failed to acquire improved ethanol tolerance but expressed other novel properties of S. cerevisiae, suggesting that karyogamy was impaired after internuclear gene transfer. PMID- 1288842 TI - Utilization of tartaric acid and related compounds by yeasts: taxonomic implications. AB - A survey of yeasts capable of growing on L(+)-tartaric acid as the sole source of carbon and energy showed that this organic acid is assimilated by a significant number of species of basidiomycetous affinity and is seldom utilized by ascomycetous yeasts. This conclusion was further supported by the fact that among approximately 100 isolates from various natural substrates, using selective media with L(+)-tartaric acid, only one strain of ascomycetous affinity was obtained. In a more comprehensive survey 442 yeast strains belonging to 138 species, mostly of basidiomycetous affinity, were also screened for the assimilation of different aldaric acids: D(-)-tartaric acid, meso-tartaric acid, L(-)-malic acid, D(+) glucaric acid (saccharic acid), and galactaric acid (mucic acid). L(+)-Tartrate was the most frequently utilized tartaric acid isomer (55% of the total number of strains of basidiomycetous affinity belonging to either the Tremellales/Filobasidiales or the Ustilaginales) when compared with the D(-) and meso forms, which were assimilated by 12 and 18% of the total number of strains, respectively (mainly of tremellaceous species). Saccharic acid was utilized by about 75% of the total number of species of Tremellales affinity and by less than 20% of the ustilaginaceous species. Assimilation of mucic acid occurred in more than 50% of the tremellaceous species and only in 5% of the species related to the Ustilaginales. These tests, not used in standard yeast identification sets, appear to contribute to distinguishing taxa at or above the species level. PMID- 1288843 TI - Effects of potassium sorbate on growth patterns, morphology, and heat resistance of Zygosaccharomyces rouxii at reduced water activity. AB - A study was made of the effects of potassium sorbate on growth, morphology, and heat sensitivity of an osmotolerant yeast, Zygosaccharomyces rouxii, grown in media (water activity (aw) 0.93) supplemented with glucose and sucrose. Growth patterns of Z. rouxii in YM broth supplemented with glucose (YMBG) and sucrose (YMBS) were similar, although increased potassium sorbate concentration in both media resulted in decreased growth rates. Growth in YMBS containing potassium sorbate was not as prolific as that in YMBG containing potassium sorbate. Inhibition of growth was indicated by decreased absorbance (at 600 nm) of cells grown in YMBS and in YMBG and YMBS supplemented with potassium sorbate at 600 or 1000 micrograms/mL. Slight decreases in cell size and alteration of cellular morphology were associated with increased potassium sorbate concentration. Plasmolysis increased as potassium sorbate concentration was elevated in YMBS but not in YMBG. Tolerance of Z. rouxii to potassium sorbate was enhanced by previous adaptation of cells in media with elevated potassium sorbate concentrations. Heat resistance of cells unadapted to potassium sorbate showed little or no increase regardless of culture age, but increased substantially in cells grown in media containing potassium sorbate, particularly YMBS. PMID- 1288844 TI - Changes in ribosomal proteins during colony development in Streptomyces. AB - The structure and functionality of the ribosomal subunits of the substrate and the aerial mycelium of Streptomyces antibioticus were compared. Using SDS-PAGE and HPLC, several differences between the ribosomal protein pattern from both stages of development were observed, including a clear decrease in the L7/L12 content of the aerial mycelium. The activity of the aerial mycelia ribosomes was also decreased when compared with that of the substrate mycelium. This effect was more pronounced in the 50S subunit. These results suggest that during cell differentiation in Streptomyces important changes occur at the ribosomal level, particularly in the transition from the substrate to the aerial mycelium. PMID- 1288845 TI - Promotion of apple tree growth and fruit production by the EBW-4 strain of Bacillus subtilis in apple replant disease soil. AB - A field trial was conducted near Kelowna, British Columbia, to determine the effect of biological treatments alone and in combination with formalin fumigation in apple replant disease soil. The response was measured by the increase in cross sectional trunk area, total shoot growth, and fruit yield of McIntosh apple trees on M.26 rootstock. The postplanting drench application of strain EBW-4 of Bacillus subtilis alone was consistently effective in increasing cross-sectional trunk area for 5 years, total shoot growth for 4 years, and fruit yield for 3 years. The biological agent EBW-4 of B. subtilis in combination with formalin fumigation was also effective in promoting total shoot growth and cross-sectional trunk area. The application of formalin fumigation alone was effective in increasing shoot growth for 2 years and cross-sectional trunk area for 1 year only. This treatment did not increase fruit yield for 3 years. The consistent performance of strain EBW-4 of B. subtilis during 1986-1991 indicates that this bacterium has the potential for biological control of replant disease under orchard conditions in the Okanagan Valley of British Columbia. PMID- 1288846 TI - Heat-shock response in Fonsecaea pedrosoi, a pathogenic fungus. AB - Using two-dimensional electrophoresis we have investigated the heat-shock response in a pathogenic fungus, Fonsecaea pedrosoi. Fungal cultures were transferred from 37 to 45 degrees C for either 30 or 90 min and then returned back to the initial temperature. Analysis of the total proteins resolved on two dimensional gels indicated important changes in the accumulation of several peptides according to the duration of treatment and the temperature. The 30-min incubation at 45 degrees C resulted in the induction of several new proteins, whereas other proteins were either increased or decreased. These inductions and repressions of proteins (called heat-shock and heat-stroke proteins, respectively) were either specific to this time period or still present after a 90-min incubation. In addition, the 90-min incubation period led to the enhancement of several proteins, which were therefore called late heat-shock proteins to distinguish them from the early ones detected after 30 min. Finally, when cultures were shifted back to 37 degrees C most of the heat-shock proteins decreased or disappeared; in parallel, most of the heat-stroke proteins were reinduced at this time. These results are in good agreement with previous studies on the heat-shock response and provide additional evidence that this phenomenon is highly conserved among species. PMID- 1288847 TI - Flocculation of Saccharomyces cerevisiae: inhibition by sugars. AB - Flocculation is governed by the competition between electrostatic repulsion (nonspecific interactions) and polysaccharide-protein bonds (specific interactions). In our study, the inhibition of flocculation by sugars for 12 strains of Saccharomyces cerevisiae leads us to extend the classification described in the literature and to define three groups of yeasts: flocculation mannose sensitive (MS), flocculation glucose-mannose sensitive (GMS), and flocculation mannose insensitive (MI). Only the first two groups showed specific interactions between proteins and mannans. n the MI group, the sugars tested did not inhibit flocculation. To characterize the particularities of the stereochemistry of the cell-wall proteic receptors of strains belonging to the MS and GMS groups, 31 sugars were used as inhibitor probes on two representative strains. The results show that the lectin specificity of strains belonging to the GMS group is less restricted regarding C-1 and C-2 hydroxyl groups than the lectin from strains belonging to the MS group, which interacts with all of the hydroxyl groups of mannopyranose. The two groups also differ with respect to inhibition by sugars: strains belonging to the MS group are partially inhibited whereas strains of the GMS group are completely inhibited. We observed that the presence of ethanol increases sugar fixation by strains from the MS group, but not from the GMS group. Moreover, both receptors interact with disaccharides, provided the two monomers are linked by an alpha(1-4), alpha(1-3), or alpha(1-2) bond. PMID- 1288848 TI - Enzyme activities of D-glucose metabolism in the fission yeast Schizosaccharomyces pombe. AB - The activities of key enzymes that are members of D-glucose metabolic pathways in Schizosaccharomyces pombe undergoing respirative, respirofermentative, and fermentative metabolisms are monitored. The steady-state activities of glycolytic enzymes, except phosphofructokinase, decrease with a reduced efficiency in D glucose utilization by yeast continuous culture. On the other hand, the enzymic activities of pentose monophosphate pathway reach the maximum when the cell mass production of the cultures is optimum. Enzymes of tricarboxylate cycle exhibit the maximum activities at approximately the washout rate. The steady-state activity of pyruvate dehydrogenase complex increases rapidly when D-glucose is efficiently utilized. By comparison, the activity of pyruvate decarboxylase begins to increase only when ethanol production occurs. Depletion of dissolved oxygen suppresses the activity of pyruvate dehydrogenase complex but facilitates that of pyruvate decarboxylase. Acetate greatly enhances the acetyl CoA synthetase activity. Similarly, ethanol stimulates alcohol dehydrogenase and aldehyde dehydrogenase activities. Evidence for the existence of alcohol dehydrogenase isozymes in the fission yeast is presented. PMID- 1288849 TI - Cyanobiont diversity within and among cycads of one field site. AB - Limited diversity was found among cyanobionts from a cultivated population of cycads at a field site in Florida. All isolates were classified as Nostoc but were different from the one Nostoc species found in the soil. These cyanobacteria were root endophytes of several plants of Zamia integrifolia and one of Dioon. The isolates were similar morphologically and in their reactions to four fluorescein isothiocyanate conjugated lectins. Electrophoretic protein profiles and zymograms distinguished one cyanobiont and the soil Nostoc. A tenacious Anabaena epiphyte was also discovered inhabiting the surfaces of root nodules. PMID- 1288850 TI - Cranial vault and skull base changes in shunt-treated hydrocephalic children. PMID- 1288851 TI - Angiographic findings of ischemic stroke in children. AB - A cooperative study was undertaken in the Tohoku district of Japan to investigate the relatively rare phenomenon of cerebral infarction in children. The purpose of the present paper is to describe the cerebral angiographic findings in 48 children whose ischemic lesions were confirmed by CT scan. The majority of lesions were considered to be idiopathic. The areas of cerebral infarction appearing in the CT scans were located in the territory of the middle cerebral artery including the basal ganglia. Angiographical abnormalities were observed in 40 patients (83%). The majority occurred in the supraclinoid portion of the internal carotid artery and in the cisternal portion of the middle and anterior cerebral arteries. Multiple lesions, such as in the C1, A1, and M1 or the C1, M1, and M2 segments were observed in 22 cases. These lesions generally appeared in continuation; no bilateral intracranial lesions were observed. Repeated angiography was performed in 22 cases, and in 55% of these some recovery of the lesions was seen. PMID- 1288852 TI - Multiple cerebral arteriovenous shunts in children: report of 13 cases. AB - The authors present a series of 13 multiple arteriovenous malformations (MAVMs) in the pediatric population (16.9% of their overall series of brain AVMs in this group). Two types of MAVMs can be distinguished: congenital and acquired. Congenital MAVMs may be of the nidus or fistula type. They may be uni- or bilateral, placed in one or several cerebral lobes, separated or close one to another, or even systematized (Wiburn-Mason syndrome). The symptoms created by these MAVMs are the same as those encountered in the presence of other AVMs, with hemorrhage as revealing symptom in 31% of patients. The responsibility of one particular nidus in the onset of clinical signs is often difficult to determine. From an angioarchitectural point of view, it seems that venous drainage changes are mainly responsible for the symptomatology. The natural history of these MAVMs is difficult to assess; spontaneous regression has been noted in 15% of cases. Acquired cerebral MAVMs can be due to angiogenesis ("sprouting" or "non sprouting") around a true AVM because of previous hemorrhage or ischemia, or to pial shunts associated with dural arteriovenous malformations. The treatment of MAVMs is difficult. Embolization seems to the authors the best therapeutic modality available, as surgery or radiosurgery are often unable to treat these multifocal lesions. Anatomical cure is rarely obtained; the therapeutic strategy has to be targeted on the symptomatic lesions. PMID- 1288853 TI - Late MRI after head injury in children: relationship to clinical features and outcome. AB - To characterize the brain pathology in relation to long-term outcome after pediatric head injury, 55 children were studied by magnetic resonance imaging (MRI) at least 3 months after sustaining moderate to severe closed head injury (CHI). Thirty-nine of the patients had abnormal signal intensity consistent with residual brain lesions, including 28 children with lesions involving the frontal lobes. The clinical features of children with frontal lesions, extrafrontal lesions, and diffuse injury were compared. The analysis disclosed that children with frontal lobe lesions were more frequently disabled than children who sustained diffuse injury. Our MRI findings indicate that residual brain lesions are more common after moderate to severe CHI in children than previously thought and that the frontal lobes are most frequently involved. Further investigation is indicated to elucidate whether distinctive cognitive and behavioral sequelae are associated with frontal lobe lesions in children. PMID- 1288854 TI - Proliferative assessment of craniopharyngioma and epidermoid by nucleolar organizer region staining. AB - The histologic distinction between craniopharyngioma and epidermoid is equivocal. Eight craniopharyngiomas and ten epidermoids (including three dermoids) as well as nine rat (Wistar) abdominal skins that acted as control were investigated by a silver colloid method for nucleolar organizer regions (Ag-NORs). The mean number of Ag-NORs in at least 200 cells of both basal (columnar) epithelial cells and suprabasal (prickle) cells was evaluated. It was found that the mean number of Ag NORs in basal cells of epidermoid and rat skin was significantly greater than that in suprabasal cells (P < 0.001 in nine of ten epidermoids and in all rat skins). On the other hand, of eight craniopharyngiomas, the mean Ag-NOR number in basal cells was not significantly different from that in suprabasal cells in five cases, and, further, the former was significantly smaller than the latter in the other three cases (P < 0.01 in two and P < 0.05 in one). These findings suggest that a stepwise maturation of the epithelial cells like that in mammalian skin epidermis exists in epidermoids but not in craniopharyngiomas. In craniopharyngiomas, the maturation of the epithelial cells seems to be considerably limited or lost from the aspect of proliferative potential as assessed by Ag-NOR score, which indicates neoplastic growth of craniopharyngiomas. Ag-NOR staining may thus be a useful method to distinguish craniopharyngioma from epidermoid. PMID- 1288855 TI - A new method for the creation and measurement of experimental craniosynostosis. AB - Craniosynostosis is described as a condition in which the premature closure of one or more cranial sutures is exposed as a skull deformity alone or accompanied by neurological disturbances. According to previous research it seemed possible to create an experimental model for investigating the disease by simply resecting a suture in a newborn rabbit. We resected 16 coronal sutures in 16 newborn rabbits and had the skulls investigated for shape and histology up to 6 months of age. A clear deformity at the cranial vault could be detected. The fused site of the suturectomy later on presented a suture-like structure which was macroscopically distinct from a normal skull suture. The procedure is thus established, first, for investigating procedures for treating craniosynostosis in the growing skull, and, secondly, for studying the pathophysiology of craniosynostosis. PMID- 1288856 TI - Chronic subdural hematoma in utero. Report of a case with survival after treatment. AB - A case of chronic subdural hematoma and hydrocephalus diagnosed in utero is presented. No history of trauma could be elicited. Laboratory investigations failed to show a coagulation disorder. Both the hematoma and hydrocephalus were surgically treated 8 days after delivery. At 14 months of age the child is showing moderately delayed development. The literature is reviewed and discussed. The importance of correct antenatal diagnosis is stressed. PMID- 1288857 TI - Spinal epidural meningioma in a child. AB - A case of spinal epidural meningioma in a 14-year-old girl is presented. Myelographic and computed tomographic findings led to the preoperative diagnosis of a metastatic lesion. Histological examination revealed the tumor to be a meningioma. Total resection was accomplished and the patient made a very good neurological recovery. A review of the literature reveals that these tumors have rarely been reported, especially in childhood. PMID- 1288858 TI - Biochemical diagnosis of Canavan disease. AB - Canavan disease (CD) is a rare autosomal recessive disorder characterized by macrocephaly and progressive leukodystrophy. Up to now biopsy or necropsy were required to define the diagnosis. Recently the disease has been related to N acetylaspartic aciduria and deficiency of aspartoacylase, an enzyme possibly involved in the myelin synthesis. These biochemical findings have provided a diagnostic marker for the disease. We report a new case of infantile CD in which the demonstration of N-acetylaspartic aciduria and a marked deficiency of aspartoacylase activity confirmed the diagnosis. PMID- 1288860 TI - Of humour, music, anger, speed, and excuses: reflections of an editorial team after one year in office. PMID- 1288859 TI - Recurrent intrinsic brain stem epidermoid cyst. AB - The authors report the case of a 14-month-old baby boy with an epidermoid cyst located entirely within the pons and medulla, without an exophytic component. The lesion was examined by computed tomography and magnetic resonance imaging. The child was operated upon three times after two recurrences of the lesion. A suboccipital, subtonsillar approach was used for the first and second procedures and a transtemporal approach for the last one. Excision was thought to be complete the first time, since a solid tumor was found and removed in a large cyst. The cyst wall was not identified. No tumor was found during the second procedure despite recurrence of the cyst, which was drained without an attempt to remove the cyst wall. Finally the cyst recurred with a large tumor in the cyst wall which was again totally removed. Consistent with the high mortality of brain stem epidermoid cysts in the literature, the child eventually died. The therapeutic problems, surgical options, and consequences are discussed. PMID- 1288861 TI - Did Wolff, Parkinson and White mind their Ps and Qs? PMID- 1288862 TI - Eponyms, priority, and attribution. PMID- 1288863 TI - Developmental changes in energy substrate use by the heart. AB - Marked changes in intermediary metabolism occur during development of the heart. In the fetus, the heart utilises lactate and glucose as its main energy substrates, while in the adult, fatty acids are the main energy substrate. The transition from carbohydrate to fatty acid metabolism is a complex process which involves maturation of mitochondrial processes and dramatic changes in circulating levels of fatty acids and lactate. In addition, developmental changes in the use of energy substrates also involve changes in the regulation of the enzymes involved in both carbohydrate and fatty acid utilisation. This paper reviews these changes in intermediary metabolism which occur during myocardial development. The metabolic differences that exist between immature and adult hearts may explain the observed differences in the ability of immature hearts to withstand hypoxaemia or ischaemia. PMID- 1288864 TI - Effects of exogenous oxygen derived free radicals on myocardial capillary permeability, vascular tone, and incidence of ventricular arrhythmias in the canine heart. AB - OBJECTIVE: The aim was to examine the effects of exogenous oxygen derived free radicals on myocardial capillary permeability for a small hydrophilic indicator, postischaemic vascular tone, and the occurrence of arrhythmias in the canine heart in vivo. METHODS: Free radicals were generated by simultaneous intracoronary infusion of hypoxanthine and xanthine oxidase into normally perfused myocardium, and at reperfusion following five minutes of coronary occlusion, respectively, in 20 anaesthetised open chest dogs. Myocardial capillary extraction for 99mTc-DTPA, plasma flow rate, and the interstitial washout rate constant were measured by the single injection, residue detection method, and the capillary permeability-surface area product (PS) was calculated. The maximum plasma flow during reactive hyperaemia was measured by the local 133Xe washout method. RESULTS: Hypoxanthine and xanthine oxidase infusion into normally perfused myocardium induced a 15% decrease in capillary extraction (p = 0.05), a 24% decrease in PS (p < 0.01), and a 23% decrease in the interstitial washout rate constant (NS) two minutes after the end of the infusion. When hypoxanthine and xanthine oxidase were infused into postischaemic myocardium, 86% of animals developed sustained ventricular arrhythmias, in contrast to none in control experiments (p < 0.05). The maximum plasma flow was 363% of preocclusive values in control experiments v 268% in hypoxanthine + xanthine oxidase experiments (p < 0.05). CONCLUSIONS: In normally perfused hearts, intracoronary infusion of hypoxanthine and xanthine oxidase induce a decreased capillary extraction, suggesting a reduced capillary surface area. In postischaemic myocardium these substances cause a decreased vasodilatation in the initial phase of reactive hyperaemia, and induce ventricular arrhythmias. PMID- 1288865 TI - Intimal proliferation in an organ culture of human internal mammary artery. AB - OBJECTIVE: Intimal smooth muscle cell proliferation is an early feature of atherosclerosis. Its progression is difficult to monitor in humans and previous studies have mostly relied on necropsy material. The aim of this study was therefore to establish whether intimal proliferation occurred in an organ culture of human internal mammary artery. METHODS: Segments of freshly isolated internal mammary artery were maintained din standard tissue culture medium containing 30% calf serum for 14 d. Tissue viability (measured by ATP concentration) was maintained during processing and throughout the culture period [211(SEM 28) nmol ATP.g-1 wet weight on d 1 v 208(27) on d 14]. RESULTS: Histological transverse sections of cultured internal mammary artery showed the development of a neointima containing smooth muscle cells identified by immunocytochemistry for alpha actin. Pulse labelling of cultures with [3H]-thymidine showed proliferating cells predominantly in a neointimal layer with few dividing cells in the media. Cultured de-endothelialized vessels showed less neointimal thickening than cultured freshly isolated vessels [16(3) v 36(5) microns, p < 0.0025] as well as a reduced number of dividing cells per mm of neointimal length [3.1(0.6) v 5.5(1.1), p < 0.05]. CONCLUSIONS: Intimal proliferation occurred in organ culture of internal mammary artery. There is evidence for a factor derived from the endothelium, which may be important in the development of intimal proliferation. PMID- 1288866 TI - Ischaemic preconditioning is not dependent on neutrophils or glycolytic substrate at reperfusion in rabbit heart. AB - OBJECTIVE: The aim was to determine whether reperfusion with either neutrophil free reperfusate or perfusate containing only pyruvate as the metabolic substrate would alter the protection against infarction afforded by preconditioning. METHODS: Rabbit hearts (n = 4-14 per group) underwent 30 minutes of regional ischaemia followed by 120 minutes of reperfusion. Blood reperfused groups experienced both ischaemia and reperfusion in situ while Krebs reperfused groups experienced regional ischaemia in situ but were reperfused with Krebs buffer in vitro. In another group, glucose in Krebs buffer was replaced by pyruvate. RESULTS: Preconditioning with 5 minutes regional ischaemia caused smaller infarct size in the blood reperfused hearts: 43.0(SEM 5.4)% v 8.8(4.2)%. In Krebs reperfused hearts, preconditioning caused a similar reduction of infarct size [49.9(2.5)% v 22.9(4.3)%] which was not different from that seen in the blood reperfused hearts. Replacing the glucose in the Krebs buffer by pyruvate also had no effect on infarct size in either the control or the preconditioned hearts [40.9(6.1)% v 11.8(5.2)%]. Histology of the ischaemic zones revealed 59.6(15.0) neutrophils per 10 high power fields in hearts reperfused in situ but only 2.6(0.6) in Krebs reperfused hearts, equal to the numbers in nonischemic blood perfused myocardium [2.8(0.9)]. CONCLUSIONS: The mechanism of preconditioning is not due to attenuation of neutrophil function during reperfusion. Furthermore, substituting pyruvate for glucose in the reperfusate did not prevent the protection against infarction afforded by ischaemic preconditioning. PMID- 1288867 TI - Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery. AB - OBJECTIVES: The existence of decreased aortic compliance due to arteriosclerosis has been documented in patients with coronary artery disease. The aim of this study was to investigate the effects of decreased aortic compliance on coronary artery disease. METHODS: To simulate coronary artery disease, a fixed stenosis was made in the left circumflex coronary artery in dogs. Ten anaesthetised open chest dogs were used. Aortic compliance was decreased by banding the thoracic aorta with adjustable plastic rings. The level of coronary stenosis was adjusted to reduce the baseline flow by no more than 10% but enough to eliminate reactive hyperaemia induced by a 10 s occlusion. Measurements of haemodynamics, regional myocardial segment length, subendocardial ECG, and myocardial tissue PO2 were performed at five stages (initial control stage, rest and pacing stages without aortic banding, and rest and pacing stages with the aortic banding). RESULTS: Haemodynamic variables were not changed at any stage, except for increased pulse pressure secondary to the aortic banding. During pacing with aortic banding, subendocardial PO2 (Endo) levels were decreased, and subepicardial PO2 (Epi) levels were increased, compared to those without the aortic banding [Endo: 43.2(SD 9.8) v 36.8(10.0) mm Hg, p < 0.05; Epi: 34.0(11.5) v 44.4(7.9) mm Hg, p < 0.05]. ST elevation on the subendocardial ECG was greater, and myocardial segment shortening was less with the aortic bandage during pacing. CONCLUSIONS: When the work of the heart is increased, a decrease in aortic compliance tends to compromise ischaemic myocardium further in the presence of an induced stenosis of a major coronary artery. PMID- 1288868 TI - Atrial contractility affects phasic blood flow velocity of atrial small vessels in the dog. AB - OBJECTIVES: The aim was to evaluate the relative contribution of atrial muscle contraction and atrial pressure to the phasic patterns of left atrial arterial and venous flows. METHODS: Using a laser Doppler velocimeter, blood velocities were measured in the atrial small arteries and veins (outer diameter: 150-500 microns) in anaesthetised open chest dogs (n = 21). The velocity sensor was fixed on the vessel surface with a drop of cyanoacrylate glue when good quality Doppler signals were consistently observed. Left atrial pressure and the contractility of the left atrium were changed by premature ventricular contraction and by intracoronary injection of isoprenaline (0.5 microgram), respectively. RESULTS: Premature ventricular contraction increased left atrial pressure significantly during arterial velocity measurements from 8.1(SD 2.7) to 16.4(1.3) mm Hg and during venous measurements from 8.2(1.2) to 14.3(3.7) mm Hg. However, premature ventricular contraction did not change the blood velocity patterns, the maximum deceleration rate of the systolic velocity wave in arteries, or the maximum acceleration rate of the systolic velocity wave in veins. Although isoprenaline did not change the left atrial pressure, it decreased minimum arterial blood velocity during atrial systole, from 3.3(3.4) to -2.5(3.2) cm.s-1, and increased maximum venous blood velocity from 15.9(5.5) to 19.2(7.4) cm.s-1. Isoprenaline also increased both the maximum arterial systolic velocity deceleration rate, from 90(45) to 234(143) cm.s-2, and the maximum venous systolic velocity acceleration rate from 356(230) to 763(366) cm.s-2. CONCLUSIONS: (1) Left atrial pressure is not a major determinant of the blood flow patterns of the atrial arteries and veins, and therefore it may not closely reflect pressure around mural vessels. (2) Atrial contractility affects the blood flow patterns of the atrial arteries and veins. PMID- 1288869 TI - Neutrophils and preconditioning. PMID- 1288870 TI - [The modern role of the Institute of Hematology and Blood Transfusion in the health care system]. PMID- 1288871 TI - [Genius loci]. PMID- 1288872 TI - [40 years' of the Institute of Hematology and Blood Transfusion]. PMID- 1288873 TI - [Use of cytogenetic and molecular biology in the detection of chronic myeloid leukemia]. AB - The examination of the presence of Ph chromosome and of the fused gene BCR-ABL in patients with chronic myeloid leukemia (CML) is significant for the precise diagnosis and in some cases for the prognosis of the disease. We examined peripheral blood for the presence of BCR-ABL fused gene by polymerase chain reaction (PCR) in eight patients with CML consecutively cytogenetically studied before and after the bone marrow transplantation and in two patients treated with interferon. Southern blot analysis was performed before BMT in two patients and the molecular rearrangement of Ph chromosome was found. In all cases our results have proved that cytogenetic and recombinant DNA evaluations confirm each other. Due to the high sensitivity of PCR technique the minimal residual leukemia can be detected. PMID- 1288874 TI - [Fibrinogen seen as an independent cardiovascular factor from the molecular aspect]. AB - The blood protein fibrinogen is one of the main independent cardiovascular risk factors and it is very likely that an increased fibrinogen level is not the consequence of cardiovascular disease but its direct cause. Fibrinogen participates actively in many processes in the organism and undergoes various changes of the molecule but it is not known what is the molecular background, why even a slight increase of the fibrinogen level is so dangerous as regards increased risk of cardiovascular attacks. In the present work the authors compared, using monoclonal antibodies, the rate of release of fibrinopeptides A and B (FpA, FpB) by the action of thrombin from fibrinogen in solution and from fibrinogen adsorbed to a solid surface. The authors revealed that the rate of FpB breakdown from sorbed fibrinogen, contrary to fibrinogen in solution is comparable to the release rate of FpA and does not depend on the release of FpA (except for competitive inhibition). The release of FpB from sorbed fibrinogen thus takes place, contrary to fibrinogen in solution, at a significant recordable rate from the very onset of thrombin action. Fibrinogen adsorption to a solid surface is associated with conformation changes which cause this effect and which lead to the formation of a two-dimensional formation formed by fibrinogen after its interaction with the surface of activated platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288875 TI - [Aberrations of the p53 antioncogene in malignant tumors]. AB - The results of the present study of the p53 antioncogene in a broad panel of human cell lines (n = 32) and biopsy specimens (n = 435) from both normal and tumour tissues can be summarized as follows: 1. Cells in primary cultures from normal tissues express very low levels of the p53 protein while strong nuclear accumulation of p53 can be seen in all SV 40 transformed human cell lines and the vast majority of tumour--derived cell lines studied. 2. Similarly, in human tissues strong nuclear p53 expression is found in high proportion of malignancies of various histogenesis, in contrast to benign lesions, nonmalignant tissues surrounding malignant tumours and normal tissues in which the p53 protein levels remain below the limits detectable by common immunohistochemical methods. 3. Sequence analysis of p53 mRNA amplified by polymerase chain reaction (PCR) revealed point mutations in the central region of the p53 gene in several cancer cell lines. Furthermore, very good correlation was found between the presence of such mutations and accumulation of the mutated p53 protein. This study confirms and extends our current view of p53 as the gene most frequently altered in human cancer and suggests that simple immunohistochemical methods can be used to screen for aberrations of this antioncogene. PMID- 1288876 TI - [Ferrochelatase gene expression in erythroid cells]. AB - The mRNA level for ferrochelatase was assessed in the total cytoplasmic RNA isolated from mouse erythroleukaemic cells, line 707, in the course of induction of erythroid differentiation with hexamethylenebisacetamide and from spleen cells of mice in different stages of erythroid differentiation after phenylhydrazine administration. The level of this mRNA increased after five days of induction of erythroleukaemic cells about six times. An even more marked increase of the mRNA level for ferrochelatase (13.5X) was found in the total cytoplasmic RNA isolated from erythropoietic spleen cells of mice after induction of haemolytic anaemia by phenylhydrazine. Haem synthesis inhibitors (succinylacetone, isonicotinic acid hydrazide and penicillamine) caused a reduced gene expression for ferrochelatase in erythroleukaemic cells of mice induced with hexamethylenebisacetamide. Conversely addition of precursors of haem synthesis (5-aminolaevulinic acid or protoporphyrin IX) led to an increased mRNA synthesis for ferrochelatase. In addition to protoporphyrin synthesis the supply of another substrate, iron, is decisive for the gene expression ferrochelatase. Iron chelators (desferrioxamine or pyridoxal isonicotinoylhydrazone) reduced and iron donors (iron bound to transferrin or pyridoxal isonicotinoylhydrazone) enhanced mRNA synthesis for ferrochelatase. Added haemin reduces mRNA synthesis for ferrochelatase in fully induced erythroleukaemic cells but increases the gene expression ferrochelatase in the course of induction of erythroid differentiation because it acts as an inducing agent. PMID- 1288877 TI - [Nucleolar asynchrony in human acute myeloid leukemia blast cells]. AB - Nucleolar asynchrony (the presence of "active" and "sleeping" nucleoli with respect to the RNA synthesis in one and the same nucleus) was noted and studied in blastic cells of the peripheral blood in patients of acute myeloid leukemias (M1 - M4 according to FAB classification) by means of light microscopy of smears after visualization of RNA containing structures. Nucleolar asynchrony seems to be a regular phenomenon in a certain number of blastic cells in the peripheral blood and has been also verified by electron microscopy. No significant difference has been noted in the incidence of blasts with nucleolar asynchrony between the peripheral blood of patients treated and untreated by cytostatic therapy at the time of taking samples for the present study: The presence of the nucleolar asynchrony/might contribute to the resistance of a certain population of leukemic blasts to the cytostatic therapy. This supposition is supported by the present experiments "in vitro" on mouse leukemic myeloblasts sensitive and resistant to Doxorubicin. The Doxorubicin resistant myeloblasts were characterized by a significantly larger incidence of the nucleolar asynchrony as compared with myeloblasts of the Doxorubicin sensitive cell line. PMID- 1288878 TI - [Antithrombin III. Structure, pathophysiology, determination and therapeutic importance]. AB - The article is devoted to the coagulation proteinases inhibitor antithrombin III which plays an important role in the processes of blood coagulation. The molecular and gene structure, physiology and pathophysiology, assays and therapeutical meanings are dealt with. PMID- 1288879 TI - [Blood transfusion preparations with a low leukocyte count. I. Preparation of thrombocyte concentrates from buffy coats]. AB - The preparation of platelet concentrates from "buffy coat" makes it possible to obtain a platelet concentrate with a low leucocyte and erythrocyte content. Concurrently prepared resuspended red cell concentrates "buffy coat" removed have moreover a low leucocyte and thrombocyte content. The mean number of thrombocytes in 1 TU of thrombocyte concentrate was 0.45 +/- 0.2 x 10(11), the leucocyte content was 0.03 +/- 0.03 x 10(9) and the red cell content was 0.8 +/- 0.7 x 10(9). The described method makes it possible to process in a rational manner blood samples into resuspended red cell concentrate a thrombocyte concentrate and plasma content. The administration of transfusion preparations with of preparation of platelet concentrates in common practice. PMID- 1288880 TI - [New methods of isolating recombinant proteins]. AB - Recombinant proteins are isolated from very complex protein mixtures present in the producing cell. The isolation process involves in general four mutually interconnected stages: 1. release of the recombinant protein from the cellular environment, 2. preparation of the specimen for separation, 3. separation, 4. qualitative and quantitative analysis of the preparation. Each of these stages is formed by a complex series of methods which destroy the cellular wall, solubilize the specimen and involve the use of suitable precipitation, chromatographic, electrophoretic, immunochemical and other techniques for separation and analysis. In the submitted paper the authors describe a relatively simple isolation of recombinant peptide used for the preparation of a diagnostic kit for AIDS. From knowledge of the sequence of nucleotides in cDNA antisense peptides can be derived which have a high affinity with the isolated protein and they can be also used for affinity chromatography. An effective isolation technique is the use of mimetic ligands on the basis of textile dyes. By their combination and possible modification it is also possible to achieve separation of the required protein from contaminating substances. The mentioned highly specific methods can be combined with classical chromatographic techniques. During every step individual chromatographic fractions are tested by SDS electrophoresis in polyacrylamide gel incl. possible use of immunoblotting a specific staining. PMID- 1288881 TI - [A registry of potential bone marrow donors]. AB - Transplantation of bone marrow is relatively successful treatment in some haematological diseases. The most suitable donor of bone marrow is a HLA genotypic identical sibling; however, roughly only 30% of patients have a suitable related donor. In order to find a HLA identical non-related donor for a maximum number of patients it is necessary to create as extensive registers as possible of potential bone marrow donors. The authors mention the possibility to obtain these donors from the ranks of regular blood donors and they mention the advantages of obtaining a register from this group of subjects. PMID- 1288882 TI - [Detection of carriers of hemophilia B]. AB - Thirty-two families with haemophilia B were divided into sub-groups based on assessment of fIX:Ag, fIX:C and the thromboplastin time with bovine thromboplastin. In confirmed carriers from these families after assessment of fIX:Ag and, fIX:C the normal range of individual sub-groups of confirmed carriers was assessed and compared with values of fiX:Ag and fiX:C of the control group. It will be possible to use these groups after their extension to assess probable carriers in sub-groups CRM+ and CRM-. In the sub-group CRMR the only criterium of transmission is a reduced fIX:C level. A prolonged TP with bovine thromboplastin in families with BM haemophilia cannot be used to assess carriers. PMID- 1288883 TI - [Results of bone marrow transplantation at the Institute of Hematology and Blood Transfusion in Prague]. AB - The first allogenic bone marrow transplantation (TKD), when for the preparation whole body irradiation was used, was implemented in the Institute of Haematology and Blood Transfusion (UHKT) in Prague in 1986. Before June 1992 36 TKD were performed incl. 28 allogenic, 2 syngenic and 6 autologous. For the first time bone marrow from a non-related donor was transplanted. Of 30 allogenic and syngenic TKD to the present time 17 patients survive, i.e. 56.6% of the whole group. According to individual diagnoses 8 patients with the diagnosis of chronic myeloid leukaemia (CML) survive, 5 of 10 patients with the diagnosis of acute leukaemia (AL) and 3 of 4 patients with the diagnosis of severe aplastic anaemia (SAA) or with Fancon's anaemia (FA) resp. The survival period of the whole group is from 1-62 months since the transplantation. The main cause of death of 8 from 13 patients who died were infections associated with acute or chronic disease of the graft against the host (GVHD). In autologous TKD the bone marrow was treated with etoposide. Of the six transplanted patients with AL five survive 1.5-30 months after transplantation. The authors present some general information of pretransplantation preparation, prevention of GVHD, its incidence and results of TKD. PMID- 1288884 TI - [Problems associated with the development of vaccines based on recombinant vaccinia virus]. AB - A collection of single and double vaccinia virus recombinants was prepared. The recombinants contained either genes for different forms of surface protein or core protein of HBV or the gene for glycoprotein I of varicella-zoster virus. Cells infected with the recombinants produced the respective foreign antigens. Specific antibodies against the heterologous antigens were induced in mice immunized with the recombinants. The insertion of the second foreign gene into the genome of single recombinants did not influence either the extent of production of the first protein in vitro or its immunogenicity for mice. PMID- 1288886 TI - [Ethics and oaths]. PMID- 1288885 TI - [Homozygosity or an undetermined antigen at the HLA locus--a problem for forensic experts]. AB - The author analyzed possibilities as regards the solution of paternity suits where paternity depends whether on the HLA 1 locus he is a homozygote or not. The authors presents a case of solution of a suit where the result depended on whether the man is a HLA-A2 homozygote or whether he has on the locus along with HLA-A2 also HLA-28 antigen. PMID- 1288887 TI - [A 100-year-old contract (1892-1992)]. PMID- 1288888 TI - [Parkinson disease. The newest etiopathogenic concepts]. AB - Three main current hypotheses, concerning etiopathogenetic mechanisms of Parkinson's Disease are presented. Various aspects of MPTP activity, free radical involvement and genetic factors are discussed. PMID- 1288889 TI - [Beta-carotene and prevention of lung carcinoma]. AB - The recent findings are critically reviewed on metabolism, pharmacokinetics, both nutritional and biochemical epidemiology, and the probable mechanisms of chemopreventive action. Some recommendations of practical value are highlighted. PMID- 1288890 TI - [Determination of NK cell activity on flow cytometry]. AB - The authors assessed the activity of NK cells on a flow cytometer using 5 carboxyfluorescein diacetate as fluorescent substrate. They examined 25 healthy subjects aged 23-52 years. In NK cellular activity the normal distribution applies and the value of NK cellular activity for the whole group as regards the ratio of effector cells to target cells was 25:1, 23.46 +/- 15.84 percentage. The authors did not detect any significant differences in the activity of NK cells in relation to age and sex. They revealed statistically significant correlations of NK activity and the number of CD16+ and CD57+ cells as well as CD57+ CD3- cells. The optimal ratio of effector and target cells for assessment of NK activity was 25:1. Assessment of NK activity on a flow cytometer can be considered an equivalent substitute of the classical method, using radiochromium. PMID- 1288891 TI - [Correlation between urinary excretion of neopterin and levels of thyroid gland hormones in patients with goiter]. AB - The authors assessed in 18 patients with goitre the urinary excretion of neopterin and the blood level of thyroid hormones. They revealed a significant correlation between urinary neopterin excretion and the thyroxine (T4) and triiodothyronine (T3) blood level. This correlation did not apply in female patients treated with large doses of Carbimazol: these patients had a high neopterin excretion, while the thyroid hormone levels were only slightly elevated. This suggests again that Carbimazol has in addition to an antithyroid effect also an immunomodulating action. PMID- 1288892 TI - [Clinical experience with long-term administration of "essential" phospholipids in chronic active hepatitis. Review of 3 double-blind studies]. AB - The results from three double-blind studies, obtained after a 12-month treatment with Essentiale or placebo in patients (n = 85) with HBsAg positive or HBsAg negative chronic active hepatitis provide evidence of the clear improvement of the clinical and histological picture in the majority of the patients treated with Essentiale forte. PMID- 1288893 TI - [A study of the so-called skull of Mozart]. PMID- 1288894 TI - [Modern pathophysiology]. PMID- 1288895 TI - Multivesicular bodies in the transitional epithelium of the neonatal mouse urinary border. AB - The origin of late endosomes - multivesicular bodies (MVBs) in the superficial cells of 16 and 17 embryonic old transitional epithelium of mouse urinary bladder was studied by electron microscopy, lectin labelling and HRP tracing. Analysis of hexagonally structured membrane particles, WGA, and RCA I binding sites revealed structural similarity between plasmalemma, fusiform vesicles and multivesicular bodies. Early endosomes are lined by symmetric unit membrane as well as by asymmetric thickened membrane regions. Multivesicular bodies and fusiform vesicles have asymmetric unit membranes. MVBs may be derived from primary endosomes as well as from fusiform vesicles in the cytoplasm. PMID- 1288896 TI - The influence of maternal nicotine exposure on neonatal lung carbohydrate metabolism. AB - The influence of maternal nicotine exposure (1 mg/kg body mass/day) during pregnancy and lactation on energy metabolism of lung tissue of neonatal rats were investigated. The glucose turnover of the lung tissue of the neonatal rats exposed to nicotine via the placenta and mother's milk was 86.4% higher than that of the controls. Glycolysis was however suppressed by 22.7% (P < 0.01). The adenine nucleotide pool (ATP+ADP+AMP) was 32.8% higher for the lungs of the 3 week old neonates exposed to nicotine than that of the control rat lung. After 4 weeks of nicotine withdrawal glycolysis of those animals exposed to nicotine were still inhibited to the same extent than during exposure. The adenine nucleotide pool was 69.95% higher than that of the controls. It is proposed that the inhibition of glycolysis was due to the high ATP/ADP ratio of the lungs of the nicotine exposed rats. PMID- 1288897 TI - Evidence for a thymus-affecting, recessive mouse gene (sty) located between the staggerer (sg) and short-ear (se) loci on chromosome 9. PMID- 1288898 TI - Nucleolar dense granules in cytochalasin-treated conidia of Neurospora crassa. PMID- 1288899 TI - Alteration of baricity: is it necessary? PMID- 1288900 TI - Endothelium derived relaxing factor/nitric oxide. PMID- 1288901 TI - Lidocaine 0.5% spinal anaesthesia: a hypobaric solution for short-stay perirectal surgery. AB - The efficacy of subarachnoid injection of 8 ml lidocaine 0.5% was assessed in ten outpatients having perirectal surgery in the jackknife position. This solution is hypobaric, with a baricity 0.9985 +/- 0.0003 (mean +/- SD). Injections were made with the patient in the surgical position (with the upper torso at a 15 degrees downward inclination). Sensory level was tested by pinprick. Times to two-segment regression, to complete resolution of sensory analgesia, to urination, and to discharge from the recovery room were recorded. All injections produced effective anaesthesia for surgery. Lidocaine 0.5% behaves clinically as a hypobaric solution. Dermatomal levels remained low (T11 to L5) while the patients were in the surgical position (head down), but rose two to six dermatomes if the patient's head was elevated after surgery. Time to two-segment regression was 97 +/- 36 min, time until regression to S1 was 116 +/- 22 min, time to complete resolution of sensory blockade was 151 +/- 23 min, time to urination was 197 +/- 64 min, and time to discharge from the recovery room was 205 +/- 45 min. Lidocaine 0.5% provides effective spinal anaesthesia of short duration appropriate for outpatient surgical procedures. Dermatomal sensory spread of anaesthesia, and our measurements of specific gravity, indicate that this solution is hypobaric. It appears that changes in position can alter the spread of analgesia for at least one hour after injection and, thus, we caution against elevating the patient's head in the immediate postoperative period. PMID- 1288903 TI - [The measurement of pH and gases in the blood using microanalysis: the effect of storage at 4 degrees C for an hour. A study in the rat]. AB - The effects of one hour storage at 4 degrees C on micro blood gas samples (150 microliters) were studied for a wide range of values (pH: 7.11-7.58; PCO2: 26-97 mmHg; PO2: 31-503 mmHg) in 20 rats with indwelling carotid artery catheters. Blood gas values were modified by varying the composition of inspired gases: normoxia, hypocapnic hypoxia, hyperoxia, hypercapnia (in this case eight animals were anaesthetized with halothane 1.1%). One hundred and eight double micro samples were taken. For each double sample, one was analysed immediately (H0) and compared with the second sample after one hr storage at 4 degrees C (H1). The Bland and Altman method was used for the statistical analysis of results. After one hr storage at 4 degrees C, the PCO2 was slightly higher than at H0 (mean difference +/- SD: +1.08 +/- 1.7 mmHg) and arterial pH was slightly lower (mean difference +/- SD: -0.016 upH +/- 0.011 upH). These results show that for these two variables, in the range studied, one hour storage at 4 degrees C had little effect. In contrast, for arterial PO2 the mean difference between all measurements between H1 and H0 was -17 +/- 25 mmHg. If results lower than 200 mmHg (56 double samples) are considered separately, the mean difference between values at H1 and H0 was only -0.98 +/- 5.3 mmHg. For PaO2 greater than 200 mmHg (52 double samples), the mean difference was -34 +/- 26.3 mmHg; this may be due to low reproducibility of measurements of elevated PO2 levels and to the effects of cellular metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288902 TI - Haemodynamic responses to tracheal intubation following etomidate and fentanyl for anaesthetic induction. AB - The haemodynamic response to anaesthetic induction and tracheal intubation was studied in 29 patients undergoing elective myocardial revascularization surgery. All patients included in the study were anaesthetized with etomidate, 0.3 mg.kg 1. The patients were randomized to three groups: Group I received fentanyl, 2.5 micrograms.kg-1; Group II received fentanyl, 5 micrograms.kg-1; and Group III received fentanyl, 10 micrograms.kg-1. Haemodynamic variables were measured at baseline (awake), after anaesthetic induction, and at one, three, five, and ten minutes after tracheal intubation. The number of patients with haemodynamic responses to intubation (> 20% increase in heart rate or mean arterial pressure) was greater (P < 0.05) in Group I than in Groups II and III. Statistically significant, but clinically minor, decreases in mean arterial pressure and cardiac output occurred in all groups at the last three study times. The frequency of involuntary muscle movements was 14%, and all of these events occurred in patients in Group I. In conclusion, the authors recommend using fentanyl, 5-10 micrograms.kg-1 to blunt the haemodynamic response to tracheal intubation following anaesthetic induction with etomidate, 0.3 mg.kg-1. PMID- 1288904 TI - Efficacy, duration, and absorption of a paediatric oral liquid preparation of ranitidine hydrochloride. AB - The objectives of this study were to assess the clinical efficacy of a new oral ranitidine liquid preparation in reducing gastric acidity and volume, to determine the degree of absorption of the drug, and to determine the duration of drug effect. Eighty preoperative children between the ages of one and six years were enrolled in each of three centres. Each subject was allocated to one of the following groups: Group A - apple juice, 5 ml.kg-1 plus placebo liquid; Group B - apple juice, 5 ml.kg-1 plus ranitidine hydrochloride 2 mg.kg-1; Group C - water, 5 ml and placebo liquid; or Group D - water, 5 ml and ranitidine liquid 2 mg.kg 1. All study agents were administered at least two hours before surgery along with a dye marker, sulfobromophthalein 1 ml (50 mg.ml-1). Following induction of anaesthesia, gastric fluid was aspirated, and analyzed for pH, volume, and sulfobromophthalein content (as an index of the ingested fluids). A serum sample was also drawn and analyzed for ranitidine content by high performance liquid chromatography. Groups B and D had fewer subjects with pH below 2.5 and gastric volume > 0.4 ml.kg-1. The duration of reduced volume and acidity was shown to be greatest from two to four hours after drug administration. Thirty-three percent of subjects receiving oral ranitidine, 2 mg.kg-1 hydrochloride as a single dose demonstrated no measurable effect on gastric pH and volume; 28 of those subjects had adequate ranitidine serum levels. PMID- 1288905 TI - Carbon dioxide reactivity and local cerebral blood flow during prostaglandin E1- or nitroglycerin-induced hypotension. AB - The aims of this randomized study were to determine the effect of prostaglandin (PGE1) or nitroglycerin-(TNG) induced hypotension on local cerebral blood flow (LCBF) and carbon dioxide reactivity during isoflurane anaesthesia in 20 patients after subarachnoid haemorrhage (SAH) scheduled for aneurysm clip ligation. Mean arterial blood pressure decreased immediately, after giving either PGE1 or TNG. The LCBF, measured using a thermal gradient blood flowmeter, was unchanged after PGE1, while the LCBF increased after TNG infusion (control; 47.6 + 10.0, 60 min after infusion; 55.1 +/- 6.5 (P < 0.05), before clipping; 55.5 +/- 7.8 (P < 0.05)) but returned to control values after its discontinuation. Carbon dioxide reactivity, calculated from % delta LCBF/delta PaCO2 was unchanged during PGE1- or TNG-induced hypotension (PGE1; 2.13 +/- 0.9, 2.48 +/- 0.68 and 2.31 +/- 0.79%/mmHg for before, during and after hypotension respectively) (TNG; 2.08 +/- 0.68, 2.17 +/- 0.64 and 2.02 +/- 0.69%/mmHg for before, during and after hypotension respectively). Carbon dioxide reactivity correlated with presurgical neurological status (rs = -0.7, -0.648 and -0.458 for before, during and after hypotension respectively) and the initial LCBF (rs = -0.605). These results suggest that both PGE1 and TNG are useful drugs for induced hypotension for cerebral aneurysm surgery, because neither decreased LCBF. PMID- 1288906 TI - EMLA partially relieves the pain of EMG needling. AB - The aim of this study was to evaluate the efficacy of the topical analgesic cream EMLA in alleviating the pains caused by needling in electromyography (EMG). During the course of regular neurophysiology clinics, 34 Caucasian patients of both sexes, aged 21 to 69 yr (mean 38.5 +/- 11.4 SD), scheduled for electromyography, were studied. The EMLA was spread thickly on two EMG sites on each arm: E site, on the lateral dorsal aspect of the forearm and A site, on the thenar eminence. Randomization was pre-established. Whenever EMLA was applied blindly on one of the sites of the arm, the placebo was applied on the homologous site of the other arm. After at least 45 min of application (range 45-145 min, mean = 72.3 +/- 22.2), the needle was inserted into the skin and into the muscle. Then the electromyographist asked the patient to score his degree of pain on a visual analogue scale (VAS 1-10 cm) for each level of insertion. The results showed that on the skin of E site, the pain was less after EMLA than placebo (VAS = 0.75 +/- 1.36 vs 3.10 +/- 1.75, P = 0.0001). The untreated E site (placebo) was less sensitive than the untreated A site (VAS = 3.10 +/- 1.75 vs 6.09 +/- 1.96, P = 0.0001). Muscle insertion on E site was less painful on the EMLA sites than placebo (VAS = 2.83 +/- 2.45 vs 5.73 +/- 2.30, P = 0.0001). The VAS scores for skin and muscle insertion on A site were identical whether EMLA or placebo had been applied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288907 TI - Laparoscopic cholecystectomy: the anaesthetist's point of view. AB - Although the surgical advantages of laparoscopic cholecystectomy (LC) have been reported, the anaesthetic problems associated with this new technique have not been well described. For the first 101 patients undergoing laparoscopic cholecystectomy at our institution, we prospectively documented intraoperative critical observations and adverse outcomes in the PACU (Post-Anaesthetic Care Unit). In order to put the magnitude of these problems into perspective, we compared, in an identical manner, the anaesthetic management and outcomes of two more familiar surgical groups, cholecystectomy by laparotomy (C), and laparoscopy for gynaecological examination (LG). For this new procedure LC, intraoperative hypotension (12.9%), and PACU hypothermia (31.4%), nausea and vomiting (12.9%) and desaturation (10.9%) were common but excessive pain (4.0%) was rare. Patients undergoing C, who were older and less healthy, tended to have fewer incidents of OR hypotension (3.4%) but in the PACU experienced more desaturation (25.9%) and excessive pain (12.9%) (P < or = 0.05). The younger and healthier LG group had fewer problems, less OR hypotension (0.4%), and less PACU nausea and vomiting (5.7%) and desaturation (1.3%) (P < or = 0.05). However, the LG group had a similar incidence of excessive pain (4.4%). We have documented considerable postoperative anaesthetic benefits for patients undergoing laparoscopic cholecystectomy compared with conventional cholecystectomy. However, there is still considerable perioperative morbidity compared with gynaecological laparoscopies. Now that specific problems have been identified, they may be amenable to specific anaesthetic interventions. PMID- 1288908 TI - Alfentanil-midazolam anaesthesia has no electrophysiological effects upon the normal conduction system or accessory pathways in patients with Wolff-Parkinson White syndrome. AB - The effects of alfentanil-midazolam anaesthesia upon the electrophysiologic (EP) properties of normal atrioventricular (A-V) and accessory pathway (AP) conduction were studied in eight patients with Wolff-Parkinson-White syndrome during accessory pathway surgical ablation. The presence of an AP was confirmed by preoperative EP studies. Anaesthesia was induced with alfentanil (50 micrograms.kg-1) and midazolam (0.15 mg.kg-1) and maintained with an alfentanil infusion (2 micrograms.kg-1.min-1) and intermittent boluses of midazolam (1-2 mg q 15 min, PRN). Following sternotomy, a baseline EP study was performed which consisted of effective refractory period (ERP) and shortest cycle length (SCC) measurement during antegrade conduction in the AV and AP, as well as during retrograde conduction in the AP. Comparison with preoperative EP studies indicated that the administration of alfentanil-midazolam anaesthesia had no effect upon conduction or ERP in either pathway. Haemodynamic stability occurred throughout the surgical procedure with no tachyarrhythmias. We conclude that a combination of alfentanil-midazolam is suitable for general anaesthesia in patients undergoing ablative procedures for accessory pathways. PMID- 1288909 TI - Perioperative haemotherapy: II. Risks and complications of blood transfusion. AB - Major life-threatening complications following blood transfusion are rare and human error remains an important aetiological factor in many. The infectious risk from blood transfusion is predominantly hepatitis, and non-A, non-B and hepatitis C (HCV) are the most common subtypes noted. The risk of post-transfusion hepatitis (PTH) appears to be decreasing and this is attributed to both deferral of high-risk donors and more aggressive screening of donated blood. Screening for HCV is expected to decrease this risk further. The risk of HIV transmission following blood transfusion is negligibly small. There are data to suggest that perioperative blood transfusion results in suppression of the recipient's immune system. Earlier recurrence of cancer and an increased incidence of postoperative infection have been associated with perioperative blood transfusion although the evidence is not persuasive. Microaggregate blood filters are not recommended for routine blood transfusion but do have a role in the prophylaxis of non-haemolytic febrile reactions caused by platelet and granulocyte debris in the donor blood. Patients should be advised when there is likely to be a requirement for perioperative blood transfusion and informed consent for transfusion should be obtained. PMID- 1288911 TI - The divergent actions of volatile anaesthetics on background neuronal activity and reactive capability in the central nervous system in cats. AB - The effects of halothane, isoflurane, and enflurane on background neuronal activity and reactive capability in the central nervous system were studied in cats. The background neuronal activity was assessed by midbrain reticular cell firing, which was measured by the method of multi-unit activity, and the EEG in the cortex, amygdala, and hippocampus. The reactive capability was assessed by evoked responses in the visual neuronal pathway. All anaesthetics studied suppressed reticular cell firing in a dose-dependent manner, and the suppression by halothane (43.8 +/- 10.3% of control, mean +/- SD) was less than isoflurane (66.5 +/- 5.8%, P < 0.01) and enflurane (73.1 +/- 8.8%, P < 0.05) at 1 MAC. Spontaneous EEG spikes developed at 4.8% isoflurane and 3.6% enflurane anaesthesia. Phasic activation of reticular cell firing was associated with EEG spikes during isoflurane and enflurane anaesthesia, and the activation during enflurane anaesthesia was greater than during isoflurane anaesthesia (P < 0.01). Photic stimulation provoked EEG spikes and repetitive stimulation induced seizure activity only at 3.6% enflurane anaesthesia. Halothane and isoflurane suppressed stimulation induced responses in the visual neuronal pathway. The amplitudes of N1 in visual cortical evoked responses induced by photic stimulation were suppressed to 70.1 +/- 24.5% of control at 2.4% halothane and 39.3 +/- 27.3% at 4.8% isoflurane. Enflurane, at 3.6%, augmented the evoked response induced by photic stimulation (398.4 +/- 83.0% of control in the amplitude of N1). These results indicate that all the agents studied had suppressive actions on background neuronal activity in the order halothane < isoflurane = enflurane. The effects on reactive capability were divergent among agents, e.g., enflurane enhanced, halothane suppressed, and the actions of isoflurane were intermediate. We conclude that the anaesthetic effects on background activity and on reactive capability are divergent and that suppression of reactive capability is a factor in determining the ease of clinical application of the anaesthetics. PMID- 1288913 TI - The output of four modern vaporizers in the presence of helium. AB - It has been previously demonstrated that the output of calibrated vaporizers is influenced by the concentration of nitrous oxide in the carrier gas. This study was performed to determine whether helium in the carrier gas affects the output of modern calibrated vaporizers. A factorial design was used to determine the influence of carrier-gas helium concentration, carrier-gas flow rate and vaporizer dial setting on the output of four vaporizers: Ohio Calibrated Enflurane, Ohio Calibrated Isoflurane, Ohmeda Isotec 4, and Drager Vapor 19.1 Isoflurane. Three vaporizers of each model were tested. Output was converted to % of baseline so that different dial settings could be compared. For a given dial setting, baseline was defined as the output at a carrier-gas flow rate of 3 L.min 1 and helium concentration of zero. The data were analyzed using multiple linear regression. There was an effect of helium concentration on vaporizer output in all models. None of these changes was clinically important, since vaporizer output did not vary by more than +/- 10%, except at high flows and at high helium concentrations with the Ohmeda Isotec 4. It is concluded that these vaporizers can be used safely with helium. PMID- 1288912 TI - Influence of desflurane, isoflurane and halothane on regional tissue perfusion in dogs. AB - The actions of desflurane, isoflurane and halothane on regional tissue perfusion were studied using radioactive microspheres in dogs chronically instrumented for measurement of arterial and left ventricular pressure, global (left ventricular dP/dtmax) and regional (percent segment shortening) contractile function, and diastolic coronary blood flow velocity. Systemic and coronary haemodynamics and regional tissue perfusion were measured in the conscious state and during anaesthesia with equihypotensive concentrations of desflurane, isoflurane, and halothane. All three volatile anaesthetics (P < 0.05) increased heart rate and decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular dP/dtmax Myocardial perfusion was unchanged in subendocardial midmyocardial, and subepicardial regions by the administration of either dose of desflurane. No redistribution of intramyocardial blood flow (endo/epi ratio) was observed during desflurane anaesthesia. Although regional myocardial perfusion was reduced (P < 0.05) in a dose-related fashion by halothane and by isoflurane at high concentrations, redistribution of intramyocardial blood flow was not observed during halothane or isoflurane anaesthesia. All three volatile anaesthetics reduced blood flow to the renal cortex, but only desflurane produced a decrease in renal cortical vascular resistance. Hepatic blood flow decreased in response to halothane but not desflurane or isoflurane. Concomitant decreases in hepatic resistance were observed during administration of desflurane and isoflurane. Dose-related decreases in intestinal and skeletal muscle blood flow were observed during halothane and isoflurane but not desflurane anaesthesia. The results suggest that desflurane maintains myocardial, hepatic, intestinal, and skeletal muscle blood flow while halothane and isoflurane decrease regional tissue perfusion in these vascular beds to varying degrees during systemic hypotension in the chronically instrumented dog. PMID- 1288910 TI - Endothelial vasomotor regulation in health and disease. AB - The purpose of this review is to provide the anaesthetists with a comprehensive update on the endothelial-cell control of local blood flow. This single cell layer was originally thought to represent only a passive barrier. It is now evident that it plays an active role in a broad variety of biological functions. Since the discovery of the endothelial-derived relaxing factor (EDRF), it has been the subject of a considerable amount of research. It is established that EDRF is secreted continuously at a basal state and that many physical stimuli as well as vasoactive substances can modulate its secretion. Evidence presented indicates that the endogenous vasodilatation produced by EDRF is similar to that of the exogenous nitrovasodilator nitroglycerin and nitroprusside (i.e., nitric oxide). Aside from EDRF, the endothelium produces other vasodilating as well as vasoconstricting factors. A review of the physiology of the endothelium regarding the local control of blood flow is provided along with its influence upon several pathophysiological states. Also included is an overview of the influence of anaesthetic agents on endothelial function. These findings linking vasomotor control to endothelial function will help to explain pathophysiological process and may lead to new therapeutic modalities. PMID- 1288914 TI - M. Digby Leigh (1904-1975). PMID- 1288915 TI - Laryngeal mask for failed intubation in emergency caesarean section. PMID- 1288916 TI - Anaesthesia for outpatient TURP. PMID- 1288917 TI - Double aortic arch presenting as massive haematemesis after removal of a nasogastric tube. PMID- 1288918 TI - Propofol as an adjunct during emergence from general anaesthesia. PMID- 1288919 TI - Gas mask during pregnancy and labour. PMID- 1288920 TI - [The effect of acupuncture on high oxygen pressure-induced convulsion and its relationship to the brain GABA concentration in mice]. AB - This paper reports the effect of acupuncturing "Renzhong" (GV26) and "Chengjiang" (GV24) points on OHP*-induced convulsion in mice. The results are as follows: 1. Convulsion induced by 6 ATA OHP were accompanied with a decrease in the brain GABA concentration. 2. When electro-acupuncture was applied for 15 minutes prior to exposure to hyperoxic chamber, the latency of convulsions was lengthened and the symptoms of seizures were alleviated. Besides, the brain GABA concentration was also elevated remarkably. 3. Administration of vitamin B6 enhanced the effect of acupuncture on convulsions and increased brain GABA concentration. 4. The latency of convulsions was well correlated with the GABA concentration of the brain (r = 0.9867). The above results indicate that acupuncture may elevate endogenous GABA levels in the brain and prevent the hyperbaric-oxygen-induced the decrease in the brain GABA content. Therefore. It is of protective effect against oxygen convulsions. Vitamin B6 may facilitate the effect of acupuncture by improving the GABA metabolism in the brain. In short, the effect of acupuncture against oxygen convulsions may be closely related to the increase in the brain GABA levels. PMID- 1288921 TI - [Pasting acupoints with Chinese herbs applying in infant acute bronchitis and effect on humoral immune substances]. AB - This report described the clinical observation of pasting acupuncture with Chinese herbs applying in 72 infant acute bronchitis cases and regarding to the humoral immune substances such as IgA, IgM, IgG, Complement C3 The result shows high cure and improve rate. The curative effect of infantile group is higher than that of childhood one (x2 = 6.501, 0.05 > p > 0.025). All indexes of humoral immune substances, especially IgA, were increased after treatment (t = 10.50, p < 0.01). PMID- 1288922 TI - [Effects of moxibustion on experimental gastric ulcer in rats]. AB - This study was designed to determine whether moxibustion at "Shenjue" plays a role in protecting gastric mucosa in rats. The areas and histological changes of gastric ulcer were examined. The results were as follows: 1. Moxibustion pretreatment within 3 weeks significantly prevented the formation of gastric ulcer. 2. As gastric ulcer had formed, moxibustion couldn't shorten the period of recovery of gastric ulcer. The results suggested that moxibustion pretreatment at "Shenjue" had a protective effect on gastric mucosa. After the experimental ulcer had formed, however, the moxibustion had little protective effect on it. PMID- 1288924 TI - [The segmental distribution of the afferent neurons of the "zusanli" point and the caecum in rabbits--a study with the horseradish peroxidase method]. AB - Ten adult rabbits were used in this experiment. A solution of 10-20% HRP (sigma IX, RZ = 3.2) was injected into the "Zusanli" point and the subserosa of the caecum. The uptake and retrograde transmission of HRP in the afferent neurons of both the somatic and visceral nerves were traced to the spinal ganglia. The results showed that: 1. Labelled afferent neurons from the region of "Zusanli" point were found in the spinal ganglia T12-S2 with a higher concentration in L4 S2. 2. Labelled afferent neurons from the region of the caecum were found in the spinal ganglia T2-S2 with a higher concentration in T12-L2. 3. The ranges of distribution of labelled afferent neurons from the regions overlapped in the segments T12-S2. PMID- 1288923 TI - [Effect of circadian rhythm on the action of acupuncture to prevent the formation of experimental gastric ulcer]. AB - Taking rats and mice as subjects, observation had been made on the protecting action of acupuncture to prevent the gastric mucosa from experimental injury. The pH value (by accurate test paper), gastric acid output (by titration), the secretion of PG in gastric mucosa (by radioimmunoassay) were observed altogether at 1-3h, 5-7h, 9-11h, 13-15h, 17-19h and 21-23h. All of the above indices were changed along with the alternation of day and night. And the effects of acupuncture on these indices were different when giving acupuncture at different times. The action of acupuncture to prevent experimental gastric ulcer was also different at different times. It is the general regularity that puncturing at the acrophase of circadian rhythm, the effect was mainly inhibitory, while puncturing at the valleyphase, the effect was mostly excitatory. Therefore, utilizing the influence of the various phases of circadian rhythm on the acupuncture effect, to choose the optimum time giving acupuncture could be one way to promote the acupuncture curative effect. PMID- 1288925 TI - [Experimental study on the influence of acupuncture and moxibustion on interleukin-2 in patients with rheumatoid arthritis]. AB - Rheumatoid arthritis (RA) is referred to the category of Bi syndromes in traditional Chinese medicine. It is regarded as an autoimmune disease, but the pathogenic mechanism is still to be clarified. In order to observe the effects of the treatment of RA with acupuncture and moxibustion on IL-2, 41 patients were divided into warming needle and point injection groups at random, and 19 healthy subjects as control group. The results showed that the IL-2 levels in two RA groups before treatment were obviously lower than that in control group (P 0.05). After treatment the IL-2 level in control group was unchanged, but increased considerably in two RA groups (P 0.01). Generally, IL-2 is considered as a very important signal for regulating immune response. Our results have shown that the decrease of IL-2 in patients with RA should be one of main causes of internal environment disorder, acupuncture and moxibustion as a stress stimulation exerts an influence on the immunity system through neuroendocrine system to improve the IL-2 production. PMID- 1288926 TI - [Effect of electro-acupuncture on cortical and hippocampal EEG in adjuvant arthritis rats]. AB - Adjuvant arthritis (AA) rats were used as the chronic pain model. The cortical and hippocampal (HPC) EEG were recorded. The behaviour and local inflammatory reaction were observed. The results showed an arousal response of desynchronization of the ECoG and HPC EEG in the AA rats, the delta waves were decreased and beta waves increased significantly. However, the inhibited effect to the desynchronization were showed could be inhibited by the electro acupuncture (EA) on bilateral Zusanli points and morphine in the AA rats. The results suggested that the cortex and hippocampus participate in the modulating action of chronic pain, and the EA has an analgesic action. PMID- 1288927 TI - [Observations on the changes in plasma pH and kalium content and the effect of acupuncture on them in the rats with hemorrhagic shock]. AB - In the present work, the changes of pH and the kalium content of blood and the effects of acupuncturing "Renzhong" on these changes were observed in rats with hemorrhagic shock. The experimental rats were randomly divided into three groups: surgical control group, shocked control group, shocked acupuncture group. The blood pH was significantly decreased at maintaining shock for one hour (n = 30), P < 0.01; there was no change in surgical control group (n = 15), pH decreased continually with the shock time, (n = 14). But pH tended to going up again after acupuncturing "Renzhong" for 15 min (n = 16). The content of blood kalium was increased at maintainually shock for one hour (n = 26). The content of blood kalium was significantly increased with the prolonging shocked time (n = 12) or acupuncturing "Renzhong" (n = 14), P < 0.05. But there was no clear change in surgical group (n = 15). The results suggested that the acidosis condition was slightly rectified by acupuncture via modulating the respiratory function and reducing the acidic metabolites in blood of the rat with hemorrhagic shock. But the hyperkalemia produced by shock was hardly rectified by acupuncture. PMID- 1288929 TI - [Observation on 63 cases of facial paralysis treated with acupuncture]. AB - Sixty-Three cases with facial paralysis were treated mainly by acupuncture combining with point injection. The main points selected were Yangbai (GB14), Wai Jingming (BL1), Sibai (ST2), Yingxiang (LI20), Dicang (ST4), Jiache (ST6), Quanliao (ST18) and Qianzheng. The points were used alternatively. Auxiliary points: for type of deficiency of both qi and blood, Zusanli (ST36), and Sanyinjiao (SP6) were added: for type of disharmony between Ying and Wei, Fengchi (GB20) and Hegu (LI4) were added; for type of stagnancy of qi and blood, Weiguan (TE5) and Taichong (LR3) were added; for type of wind-heat stagnating collaterals, Yifeng (TH17) and Yanglingquan (GB34) were added. 10 out of 60 cases, which showed no remarkable effectiveness after two courses, injection of vitamin B1 and vitamin B12 to facial points combined with Hegu (LI4) point on opposite side was performed. Therapeutic results: 31 cases (49.2%) were cured, 15 cases (23.8%) markedly effective, 16 cases (25.4%) effective and 1 case (1.6%) ineffective. PMID- 1288928 TI - [Effect of oxytocin and cholecystokinin octapeptide (CCK-8) on electroacupuncture (EA) analgesia]. AB - The effect of oxytocin (OT) and cholecystokinin octapeptide (CCK-8) on EA analgesia was studied in rats. The increase of 20.8-39.8% and 9.0-45.0% in pain threshold was observed respectively when ICV of CCK-8 or naloxone was combined with EA, these increases were lower than that in saline-EA group significantly, while the simultaneous ICV of OT and CCK-8 or OT and naloxone in combination with EA produced the increase of 76.2-116.6% and 41.8-104.5% in pain threshold separately. These results showed that only a small part in the role of OT enhancing EA analgesia was blocked by CCK-8 and naloxone. The data suggest that the role of OT in EA was not entirely dependent upon the endogenous opiate peptides. PMID- 1288930 TI - [Comparison between of acupuncture and epidural anesthesia in appendectomy]. AB - It was a clinic comparative observation of the effects between acupuncture and epidural anesthesia in appendectomy. Eighty patients with appendicitis were randomly divided into two groups, each of 40 Patients. The results were no significant difference between two groups in successful rate. It is convinced that acupuncture on Zusanli points (ST36) has analgesia. There were less respiratory depression, hypotension, cardiac arrhythmia and less amount of liquid infusion needed than that of the epidural block during operation. Furthermore, in the group of acupuncture anesthesia, the intestinal gas excreted earlier, the analgetics and antibiotics administered were less and the rate of the wound infection were reduced after operation. These postoperative effects were significantly better than the controls. As it is of clear-cut effects of anesthesia by acupuncture with main points Zusanli and auxiliary points Hegu (LI4) and less interfered life sign in the operation, thus it is desirable to use acupuncture anesthesia in appendectomy. PMID- 1288931 TI - [Effect of electro-acupuncture on the nociceptive responses of SI cortical neurons in the rat]. AB - 1. The effect of electro-acupuncture (EA) on the responses of single SI cortical nociceptive neurons to peripheral natural stimuli were observed in unanesthetized and paralyzed rats. 2. After EA, the responses to noxious mechanical and/or thermal stimulation reduced markedly in 14 (70%) out of 20 neurons tested, and slightly increased or unchanged in the remaining 6 neurons, as compared to the responses before EA. 3. In contrast to the variation of nociceptive responses, the responses to innocuous mechanical stimulation increased in 9 neurons and unchanged in other 9 neurons, while deceased in only 2 neurons. 4. A small portion of the neurons were activated by EA stimulation, while their responses to noxious stimulation were inhibited. 5. It is considered that the selective inhibition of the nociceptive responses of SI cortical neurons might be a part of the mechanisms of acupuncture analgesia. PMID- 1288932 TI - [Inhibitory effect of electro-acupuncture on penicillin-induced amygdala epileptiform discharges]. AB - Epileptiform discharge induced by microinjection of penicillin in the rat's amygdala was attenuated after acupuncture of certain "acupoints", as revealed by reduction of frequency and amplitude. The effect of acupuncture was reversed by microinjection of naloxone or 3M-P into peritoneal cavity, thus suggesting the participation of endorphin and GABA in antiepileptic action of acupuncture. PMID- 1288933 TI - [Involvement of acetylcholine in corticofugal modulation of pain]. AB - We have found that after intraperitoneal injecting atropine the analgesic effect of both stimulating Sm I cortex and acupuncture were decreased. It suggests that acetylcholine (ACh) may be involved in the corticofugal modulation of pain. In order to elucidate this idea the effects of stimulating Sm I cortex on tail flick latency (TFL) after ventrical microinjecting atropine were investigated. The experiments were carried out on Wistar rats. Under the state of anaesthesia a pair of silver ball electrodes were put on the dura for electrical stimulating Sm I and the ipsilateral ventricle was cannulated for microinjecting atropine. Recordings were made 5-6 hours or 24 hours after operation. Immediately after cessation of stimulating SmI and 1', 2', 3.5', 5', 7.5', 10' and 15' later TFL were measured consecutively. The results were as follows: 1. The mean value of TFL was 2.44 +/- 0.11 sec (n = 20). It was prolonged (p < 0.05) within 0'-5' after stimulation of SmI. Therefore, it indicated that analgesic effects were produced by stimulating SmI cortex. 2. It was found that under the background of microinjecting atropine (10 micrograms/2 microliters) TFL remained unchanged after stimulating SmI cortex (n = 10, P > 0.05). There was a significant difference between the two treatments: simple stimulating SmI and atropine plus stimulating SmI at the same animals in TFL (P < 0.05) within 0' and 1' after cessation of stimulating SmI. It indicated that the analgesic effects of stimulating SmI cortex were decreased by blocking M-receptors. 3. Under the background of microinjecting normal saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1288934 TI - Neonatal correction of transposition of the great arteries: the Connecticut experience. AB - The treatment of transposition of the great arteries, a common congenital cardiac defect, has undergone significant development. Prior to 1989 a surgical approach which repaired the transposition at the atrial level (Senning's operation), but did not restore normal anatomy, was the procedure of choice. Since 1989 a surgical approach that restores normal anatomy (Jatene's arterial switch) has been followed. Forty-four patients have been corrected since 1979 (N = 26 Senning's operation, N = 18 arterial switch). The arterial switch patients are corrected at an earlier age, have a longer, more complex operation without a significant increase in operative mortality, intensive care, or duration of hospitalization. The prevalence or frequency of normal ventricular function and normal sinus rhythm is significantly increased over the repair at the atrial level. The frequency of pulmonary stenosis is increased. The duration of follow up for these patients is significantly shorter than for those with atrial level repair. PMID- 1288935 TI - Multivessel coronary angioplasty. AB - Multivessel coronary angioplasty is currently a revascularization alternative in selected patients with suitable anatomy. The literature on two- and three-vessel coronary angioplasty is reviewed with respect to both immediate success and long term outcome. A therapeutic strategy for performing multivessel coronary angioplasty in the individual patient is outlined. PMID- 1288936 TI - Venereal disease control needs in wartime. 1942. PMID- 1288937 TI - Reform the industry: protect the profession. PMID- 1288938 TI - Bridging the gap. II. PMID- 1288939 TI - Medical journals in the educational role. PMID- 1288940 TI - Effect of ACE inhibitors. PMID- 1288941 TI - Can pharmacological therapy influence the mortality of chronic congestive heart failure? AB - The prognosis of patients with advanced left heart failure is fairly dismal. It was not until recently that studies were conducted demonstrating the poor prognosis can be modulated by drug therapy. Of the many vasodilators tested, positive data have emerged only from trials of high-dose nitrates with hydralazine and, most importantly, angiotensin-converting enzyme inhibitors believed to constitute the biggest step forward in the treatment of chronic heart failure. The agents included in this group improve the symptomatology, increase exercise tolerance and improve the prognosis. At present, they are indicated in cases of severe heart failure, and the potential of their use in the more severe forms as well as in patients after myocardial infarction is being intensively investigated. Still, diuretic remain the mainstay of drug therapy. The role of digitalis in the treatment of heart failure is being currently reviewed; its administration is unnecessary in most patients, especially those with maintained sinus rhythm. A number of other positive inotropic drugs, both catecholamine based agents and phosphodiesterase inhibitors (amrinone, milrinone, xamoterol, enoximone) have been tested. Their effect in the chronic form, unlike acute failure, is controversial, and there is no evidence documenting improved prognosis; some studies even show an adverse trend. As almost 50% of patients with heart failure die suddenly, it would have been only logical to administer antiarrhythmics to them. However, no data demonstrating an improved prognosis are available either. Results of studies conducted to date have proved to be rather disappointing, and a study with the most promising antiarrhythmic drug- amiodarone--is still under way. PMID- 1288942 TI - Angiotensin converting enzyme inhibitors. Pharmacological and physiological background for cardiovascular treatment. PMID- 1288943 TI - Cardiac arrhythmias in chronic heart failure. AB - It has been proven that treatment of chronic heart failure (CHF) with some modern drugs is able to reduce mortality in groups of patients with the severest grades of this disease. The risk of sudden death has been unchanged, however. Out of 49 patients on long-term follow-up, 28 patients are surviving (group A) and 21 died (group B). 52.3% of the dead patients died suddenly. Eight patients in NYHA classes I-II died, all of them suddenly. Contrary to this, sudden death was the cause of death only in three of 13 patients in NYHA classes III-IV (p < 0.001). More severe heart failure was present in group B (NYHA class 2.95 +/- 0.96 vs. 2.18 +/- 0.48 in group A--p < 0.1). Antiarrhythmic drugs were given more frequently in group B (in 47.6% of pts vs. 17.9% in group A--p < 0.05). It is concluded that the occurrence of sudden death is higher in patients with less severe forms of CHF and has not been reduced by the means employed. Use of antiarrhythmic drugs may be dangerous and their indication should be based on results of a comprehensive examination. Use of the implantable cardioverter defibrillator seems to be the most promising approach in indicated cases. PMID- 1288944 TI - Renpress, Sandopril (Spirapril/TI 211-950). Summary of chemical, pharmacological and clinical properties. PMID- 1288945 TI - Radiologic changes in chronic heart failure. AB - The relationship between chest X-ray findings and NYHA classification or haemodynamic parameters (ejection fraction, end-diastolic and end-systolic volumes by echocardiography, right atrial pressure--RAP, pulmonary artery pressure--PAP and pulmonary wedge pressure--PAWP by right heart catheterization) was evaluated in 44 and 22 patients with chronic congestive heart failure, respectively. In chest X-ray, the cardiothoracic index (CTI) and authors' own classification of pulmonary congestion (PCG) of classes 0, 1 and 2 were used. A significant correlation was found between CTI and NYHA classification or haemodynamic parameters, and between PCG (classes 0 and 2) and echocardiographic parameters or right heart pressures (EDV, ESV, RAP, PAP, PAWP), but there was no significant relationship between X-ray and left ventricular ejection fraction. For a PAWP higher than 18 mmHg and PCG class 2, the sensitivity of X-ray was 86% and specificity 80%. The authors conclude that chest X-ray provides reliable information about the haemodynamic parametres, comparable to echocardiographic and catheterization data. PMID- 1288946 TI - Building the model ICU. PMID- 1288947 TI - Visions of healthcare: a view from the other side. PMID- 1288948 TI - Communication: the key to crisis prevention in pediatric death. PMID- 1288949 TI - Unstable angina: an overview. PMID- 1288950 TI - Transesophageal echocardiography: advanced technology for the cardiac patient. PMID- 1288951 TI - Nursing care of a child following an arterial switch procedure for transposition of the great arteries. AB - The restoration of the left ventricle as the systemic pump and the lack of sinus node dysfunction (assessment with the Senning or Mustard procedure) have been suggested as the major advantages of the arterial switch procedure. Although the results are encouraging, children will require follow up to assess: long-term left ventricular function; coronary ostial growth; aortic and pulmonic anastomosis growth; long-term aortic valve (anatomical pulmonary valve) dysfunction. A learning curve is inherent to a new surgical procedure. During this learning period, both surgical technique and patient selection criteria improve, resulting in reduced morbidity and mortality. The arterial switch procedure for TGA is certainly not an exception. Expert nursing assessment and intervention during the postoperative period is imperative and may reflect on the long-term outcome of these children. PMID- 1288952 TI - ICU-CCU flowsheet. PMID- 1288953 TI - When should enteral feeding begin postoperatively? PMID- 1288954 TI - Needlestick safety devices: are they 'worth' the cost? PMID- 1288955 TI - New graduates in critical care: how long do they stay? PMID- 1288956 TI - The Cruzans talk about Nancy, the critical care experience and their new mission. Interview by Michael Villaire. PMID- 1288957 TI - Systems of ethics: a perspective. PMID- 1288958 TI - A guide to evaluating hypotheses and definitions of variables. PMID- 1288959 TI - Cardiovascular disease in the elderly. AB - The current worldwide explosive increase in the numbers of older persons is unprecedented in history. In the 1990s and beyond, the preponderance of patients with cardiovascular illness will be elderly, with a substantial subset among the frail elderly, 85 years old and older. Cardiovascular disease remains the leading cause of death and disability in this population, and cardiovascular risk increases steadily with age. Pascal defined old age as "just a time that is farther from the beginning and nearer to the end." Elderly persons, with and without cardiovascular disease, vary widely in their physical, behavioral, cognitive, and emotional functioning; severity of illness; and expectations from medical care. The challenge to the clinical and research communities alike is to delineate the appropriate components of preventive, diagnostic, and therapeutic care for elderly cardiac patients in our society, interventions that are likely to relieve suffering, restore function so as to limit disability and dependency, and maintain a dignified and meaningful life-style for the end years of life. Major societal strides have been made in redefining both the onset of old age and its limitations. The eighteenth century poet, Robert Burns, wrote of his fears that he would be 45 years old at a time when life expectancy was 40 years; he saw himself as being weary, wrinkled, creeping, and joyless. For, ance that five-and forty's speel'd, See crasy, weary, joyless Eild, Wi' wrinkled face, Comes hostin', hirplin', owre the field, Wi' creepin' pace. Burns died at the age of 37 years. A more attractive option is offered by Abraham Joshua Heschel, 1907-1972. According to all the standards we employ ... the aged person is condemned as inferior. ... Conditioned to operating as a machine for making and spending money, with all other relationships dependent upon its efficiency, the moment the machine is out of order and beyond repair, one begins to feel like a ghost without a sense of reality. ... Regarding himself as a person who has outlived his usefulness, he feels as if he has to apologize for being alive. May I suggest that ... old age be regarded not as the age of stagnation but as the age of opportunities for inner growth. ... The years of old age ... are indeed formative years, rich in possibilities to unlearn the follies of a lifetime, to see through inbred deceptions, to deepen understanding and compassion, to widen the horizon of honesty, to refine the sense of fairness. PMID- 1288960 TI - Effect of probenecid on the pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in humans. AB - A total of 5 healthy volunteers were enrolled in a crossover study on the dose dependency and the effect of probenecid on pharmacokinetics of DQ-2556. They were administered intravenously 0.5 and 1.0 g of DQ-2556, and 1.0 g of DQ-2556 with oral administration of probenecid. The linearity in pharmacokinetics of DQ-2556 was confirmed up to the dose of 1.0 g. In the case of 1.0 g of DQ-2556 with probenecid treatment, the area under the serum concentration-time curve was larger, and total and renal clearances were less than those in the case of 1.0 g of DQ-2556 alone (by approximately 15% for each parameter, p < 0.01). These results demonstrated that DQ-2556 is secreted in the renal tubule, although it is excreted mainly by the glomerular filtration. PMID- 1288961 TI - In vitro evaluation of BAY Y3118, a new full-spectrum fluoroquinolone. AB - BAY Y3118, 1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8- chloro 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride, is a new fluoroquinolone with antibacterial activity against an expanded spectrum of species including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, and also anaerobes such as Bacteriodes fragilis and Clostridium perfringens. MIC90s for S. aureus, S. epidermidis, E. faecalis, and S. pneumoniae clinical isolates were 0.125, 0.25, 0.125 and 0.25 micrograms/ml, respectively. Against methicillin- and/or quinolone-resistant S. aureus, MIC50 levels of BAY Y3118 were 10- to 100-fold lower than those of tosufloxacin, sparfloxacin, or ciprofloxacin. The potency of BAY Y3118 against all members of the Enterobacteriaceae generally was equal to or 2-fold greater than that of ciprofloxacin or tosufloxacin. BAY Y3118 was also highly active against Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter spp. and Pseudomonas aeruginosa. Increasing inoculum concentrations had a minimal effect on MIC determinations. The drug was determined to be bactericidal based upon reference MBCs and time-kill curves. From the results presented here, it was concluded that this new compound surpasses other known 4-quinolones both in spectrum and activity and that its further evaluation by in vitro, in vivo, and clinical studies seems warranted. PMID- 1288962 TI - Antimicrobial activity of subinhibitory concentrations of ciprofloxacin against Pseudomonas aeruginosa as determined by the killing curve method and the postantibiotic effect. AB - This investigation used the postantibiotic effect (PAE) and killing curves to examine the antimicrobial activity of subinhibitory (1/8x, 1/4x and 1/2x MIC) and inhibitory (1x MIC) concentrations of ciprofloxacin against mucoid (M) and nonmucoid (NM) urinary isolates of Pseudomonas aeruginosa. Subinhibitory concentrations (1/8x, 1/4x and 1/2x MIC) of ciprofloxacin produced PAEs with no difference between M and NM strains. For NM strains, those with low MICs (< or = 1.0 mg/l) to ciprofloxacin produced significantly longer PAEs than isolates with high MICs (> 1 mg/l). Killing curve studies demonstrated that subinhibitory concentrations of ciprofloxacin produce little effect (1/8x MIC) or stasis (1/4x and 1/2x MIC) of growth for several hours. Only 1x MIC was bactericidal for several strains. At 1/2x and 1x MIC, bacterial inhibition was greater against NM versus M isolates. The M phenotype of P. aeruginosa reduces killing by ciprofloxacin but not the PAE. PMID- 1288963 TI - Antibacterial activity of citreamicin-alpha (LL-E 19085 alpha) against gram positive cocci. AB - In vitro antibacterial activity of 429 clinical isolates of gram-positive cocci was tested against citreamicin-alpha (LL-E 19085-alpha) by the agar dilution method. The microorganisms consisted of 313 isolates of staphylococci and 116 strains of streptococci. In vitro activity of citreamicin-alpha was compared with ampicillin, augmentin, cephalothin, erythromycin and vancomycin. MICs of citreamicin-alpha for staphylococci ranged between 0.12-4.0 micrograms/ml and 0.03-0.12 micrograms/ml for Streptococcus pyogenes. Enterococci, however, were relatively more resistant, requiring 2.0 micrograms/ml of this drug to inhibit 64% of the 62 isolates tested. In vitro activity of this antibacterial agent was far superior to that of ampicillin, augmentin, cephalothin and erythromycin, but equal to or slightly inferior to that of vancomycin. PMID- 1288964 TI - Escherichia coli resistant to ampicillin/sulbactam. AB - Escherichia coli strains resistant to ampicillin/sulbactam from hospitals in 4 different geographic locations were examined with respect to type and amount of beta-lactamase produced. A total of 5 strains was examined from each region. The isoelectric points of all of the involved beta-lactamases were 5.4, corresponding to TEM-1. Km and Vmax values of the beta-lactamases among the clinical isolates resembled those from the control TEM-1 strain. In an 18-hour broth culture the highly resistant isolates produced 3 times more beta-lactamase as compared to the ampicillin/sulbactam-susceptible isolates. However, the highly resistant strains contained approximately the same amount of plasmid DNA (size of > 6,500 bp) as the susceptible isolates. In transformation experiments, both the resistance and the degree of resistance appeared to have been transferable by plasmids. The mechanism for resistance is likely to be a baseline overproduction of TEM-1 beta lactamase due to either an alteration in the control of gene expression or simply to an increase in the number of copies of the beta-lactamase gene in the plasmids. PMID- 1288965 TI - Exposure effects of netilmicin on Enterobacter cloacae clinical isolates. AB - The effects of netilmicin exposure on two aminoglycoside (AMG)-resistant and two AMG-susceptible Enterobacter cloacae isolates were studied. It was found that 1 h incubation of bacterial suspensions with netilmicin at 16 mg/l reduces the amounts of lipopolysaccharides present on the bacterial surface. Also, netilmicin pretreatment increased both the susceptibility to normal human serum and the adhesion to human epithelial cells of all four E. cloacae strains examined. PMID- 1288966 TI - Chlorpromazine: a drug potentially useful for treating mycobacterial infections. AB - Chlorpromazine (CPZ) is one of several phenothiazines known to have antimicrobial properties. It can inhibit mycobacteria, and was reported in the early literature to improve tuberculosis clinically. CPZ was tested here for its ability to inhibit the replication of Mycobacterium tuberculosis and Mycobacterium avium in cultured normal human macrophages, as determined by counts of viable bacteria at 0, 4, and 7 days after bacterial infection of the macrophages. CPZ inhibited the intracellular bacteria at a concentration range of 0.23-3.6 micrograms/ml, and was more effective intracellularly than extracellularly. It was further tested for its ability to cooperate with isoniazid, streptomycin, pyrazinamide, rifampin, rifabutin, penicillin and ethambutol (EMB) against intramacrophage M. tuberculosis and M. avium. CPZ enhanced the effectiveness of most of the drugs tested against intracellular mycobacteria. However, the combination of CPZ and EMB did not result in augmented antimycobacterial activity. PMID- 1288967 TI - Randomized comparison of ceftriaxone versus ceftriaxone plus amikacin for the empirical treatment of infections in patients with altered host defense: microbiological and clinical evaluation. AB - Two hundred and eighty-four febrile episodes in immunocompromised patients were treated with ceftriaxone alone or in combination with amikacin. In the ceftriaxone-treated group, 60 out of 143 febrile episodes were microbiologically documented, while in the group receiving the combination therapy, there were 32 out of 140 (p = 0.0007). Gram-positive microorganisms were more common than gram negative ones, accounting for 59 of the 101 isolated bacteria. The ceftriaxone regimen appeared to have a response rate comparable to the combination regimen (73.91 vs. 78.88%). Superinfections occurred under both regimens. PMID- 1288968 TI - Inhibition of Haemophilus influenzae adherence to buccal epithelial cells by cefuroxime. AB - We studied the effect of subinhibitory concentrations of cefuroxime on the capacity of Haemophilus influenzae to adhere to buccal epithelial cells (BEC). Two encapsulated strains (serotype b) and two nonencapsulated, nontypable strains were studied. All four strains adhered strongly to BEC, with indices (mean number of bacteria adhering to a single BEC) ranging from 19 to 48. Subinhibitory concentrations of cefuroxime (serial dilutions from MIC/2 to MIC/32) were added to cultures in tryptic soy broth and their effect on adherence was tested after 18 h incubation at 37 degrees C. Adherence was diminished by more than 50% by concentrations of cefuroxime ranging from MIC/2 to MIC/8 and varied according to the strain studied. These results show that the adherence of H. influenzae to BEC is inhibited by subinhibitory concentrations of cefuroxime. PMID- 1288969 TI - Uptake of flurithromycin by human polymorphonuclear phagocytes: partial characterization of the entry mechanism. AB - The ability of flurithromycin and erythromycin to enter human polymorphonuclear phagocytes were studied and compared by a velocity centrifugation gradient technique. Both macrolides were markedly concentrated by human cells and attained cellular to extracellular concentration ratios (C/E) > or = 10. The incorporation was rapid and essentially complete after 60 min incubation. When PMNs were pretreated with formaldehyde, or incubated at low temperatures (4-25 degrees C) or at low pH, the transport ratios of both molecules were reduced. Sodium fluoride and 2,4-dinitrophenol, which decreased erythromycin uptake, did not affect flurithromycin penetration. Perturbation of cell membrane by phorbol myristate acetate, but not by formyl methionyl leucyl peptide, affected C/E ratios of both antibiotics. The addition of amino acids or nucleosides did not influence their transfer into PMNs. PMID- 1288970 TI - Activity assays of thiadiazine derivatives on Trichomonas vaginalis and amastigote forms of Trypanosoma cruzi. AB - Eight thiadiazine 1,1-dioxide derivatives were evaluated for antitrichomonal and antitrypanosomal activities. In vivo tests were performed on a murine model for trichomoniasis standardized in our laboratory. The capacity of compounds to clear visceral lesions in experimentally infected animals as well as their effects on the mortality time of mice were used as criteria for activity. One of the thiadiazines (compound 7b) showed an efficacy similar to that obtained with the reference drug metronidazole, although higher doses were required. Its toxicity on cell proliferation in tissue culture was moderate. In vitro assays on amastigote forms of Trypanosoma cruzi were carried out using cultures of Vero cells infected with metacyclic trypomastigotes. For one compound (1) trypanocidal activity resembled that of nifurtimox as assessed by microscopic counts of infected and uninfected cells. Unfortunately, this compound showed a high degree of cytotoxicity on Vero cell cultures. PMID- 1288971 TI - Plasma ammonia in patients with acute leukemia. AB - Plasma ammonia level (PAL) was studied in 43 cases of acute leukemia (AL). PAL was 39.21 +/- 26.2 mumol/L in normal controls and 38.8 +/- 16.6 mumol/L in leukemic patients before chemotherapy. High PAL was found in 40 cases after chemotherapy. Six cases showed clinical manifestations due to severe hyperammonemia, including dizziness, lethargy, confusion, coma and mental changes of various degree, and there was also respiratory alkalosis. After ammonia trapping therapy, 4 of the 5 patients recovered. The authors believe that high PAL is not uncommon after chemotherapy in leukemic patients. Respiratory alkalosis and unexplained mental and neurologic changes following intensive chemotherapy are useful clues for the diagnosis of hyperammonemia syndrome. Early diagnosis and treatment with ammonia-trapping may improve the rates of remission and survival. PMID- 1288972 TI - Insular cistern hematoma. A special type of subarachnoid hemorrhage. AB - The clinical manifestations of 20 cases of insular cistern hematoma were characterized by sudden onset violent headache, vomiting, bloody CSF, and subhyaloid hemorrhage (1/3 cases). CT scan showed semilunar high density image centering on the insular cistern with serrate internal edge. The average volume of the hematoma was 20 ml. By means of cerebral angiography, operation and/or autopsy, 7 cases were identified as aneurysm of middle cerebral artery, 6 as aneurysm of posterior communicating artery, and 2 as amyloid angiopathy. In the other 5 cases, the etiology was unknown. PMID- 1288973 TI - Effect of human growth hormone on the proliferation of human fetal islet cells in vitro. AB - In this study it was shown that 1000 micrograms/L hGH in serum-free medium promoted the attachment, spreading and formation of monolayer of islet cells. The radioactivity test indicated that hGH significantly stimulated the DNA synthesis of islet cells (P < 0.001). Furthermore, after 48 h exposure to hGH (1000 micrograms/L), both the insulin contents and release of islet cells significantly increased (P < 0.001); hGH also enhanced the responsiveness of fetal islet cells to high-concentration glucose plus theophylline stimulation (P < 0.001). However, the effect of hGH in the medium containing 10% newborn calf serum was not so prominent in comparison with that in the serum-free medium. The morphologic assay for mitotic cells showed a combination of 1000 micrograms/L hGH and 10% serum was the most efficient for inducing the mitosis, the mitotic index being 5.95%. We conclude that hGH is an important growth factor for human islet cells. PMID- 1288974 TI - Pharmacokinetics of clonazepam in developing rats. AB - Time-concentration studies of clonazepam (CZP) were performed in 7-, 14-, and 28 day-old Sprague-Dawley rats. Blood samples and brains were collected at specific intervals following a single subcutaneous (SC) injection of 2.5 mg/kg of CZP. CZP concentrations were measured both in plasma and brain samples by high performance liquid chromatography. Pharmacokinetic parameters were calculated using R-Strip for each age group. The results were compared between the age groups and with those of a similar study in our laboratory using lower dose CZP (1 mg/kg) SC injections in adult Sprague-Dawley rats. Younger rats had slower, delayed and higher peak concentrations, larger areas under the curve (AUC), longer elimination half lives (T1/2), smaller volumes of distribution (Vd) and slower clearances (C1). 28-day-old rats showed the fastest C1, smallest AUC and largest Vd. These data suggest that the pharmacokinetic behavior of CZP is age-dependent. If this is true in human, it is implicated in dosing of neonatal or pediatric patients. PMID- 1288975 TI - Effects of atrial natriuretic factor on patients with renovascular hypertension. AB - Previous studies have shown the effects of atrial natriuretic factor (ANF) on rats with renovascular hypertension (RVH). In the present study low dose alpha hANF (0.025 microgram/kg/min) was administered intravenously for 60 minutes to seven RVH patients. Results demonstrated an inhibition of renin-angiotensin aldosterone system (RAAS), reduction of plasma catecholamine and arginine vasopressin(AVP), diuresis and natriuresis, increase of hematocrit and creatinine clearance, and slight decrease of blood pressure. These results showed that most factors involved in the establishment and maintenance of RVH are affected by ANF infusion. PMID- 1288976 TI - Apolipoprotein E polymorphism and coronary heart disease. AB - Serum lipoproteins and apolipoproteins were analyzed in 199 patients with acute myocardial infarction (CCU group), and in 211 normal healthy individuals (control group). It was shown that serum lipoprotein abnormalities, especially elevated low density lipoprotein (LDL) levels, are closely related to atherogenesis in relatively young patients and in subjects with severe coronary lesions. The frequency of apo E4 was higher and that of E2 was lower in the CCU group than in the control group. Apo E mutants, E7 and E5, were also frequent in the CCU group. Subjects with an E3/2 phenotype had reduced LDL and increased VLDL levels, and those with an E4/3 phenotype had increased LDL levels in serum. These results suggest that apo E4 is a positive risk factor and apo E2 a negative risk factor for atherosclerosis. The action of apo E isoproteins to increase or decrease serum LDL levels may be one of the mechanisms of atherosclerosis. Furthermore, the effect of apo E isoforms on serum lipoproteins was evident even in childhood. The mutant apo E binding to LDL receptors were investigated to clarify the metabolism of apo E5 and apo E7. The affinity of apo E5 was twice that of the wild form of apo E3. Apo E7, however, had a lower receptor affinity than apo E3. Therefore, the authors postulate that individuals with apo E5 have increased risk of developing hypercholesterolemia and subsequent atherosclerosis. From the binding data of apo E7, the action of apo E7 is considered similar to that of apo E2. PMID- 1288977 TI - In vitro and in vivo effects of PGE2 on cementless fixation of implant. AB - The effects of prostaglandin E2(PGE2) in vivo and in vitro on cementless fixation of porous coated implant were studied. The results revealed that high levels of PGE2 in the local tissue benefit bone ingrowth in the early stage of implantation. Co-Cr-Mo alloy itself hampers the growth of osteoblasts and decreases the local secretion of PGE2. In the early stage of arthroplasty, the use of PGE2 inhibitors should be forbidden, and proper loading stimulation is preferable. High level PGE2 of local tissue in the later stage indicates bone resorption. PMID- 1288978 TI - Local changes in aluminium, calcium and phosphorus content of bone caused by alumina implant. AB - Thirty rabbits were divided equally into 5 groups randomly. A hole, 6 mm in diameter and 2 mm deep, was bored on each iliac crest. Two pieces of alumina were implanted into the hole of one side, while the opposite side served as control. These rabbits were killed on 10, 20, 40, 60 and 90 days after operation. Calcium, phosphorus and aluminium contents of iliac bone on both sides were determined by Inductively Coupled Plasma--Atomic Emission Spectrometry. The results showed that the aluminium content of the implanted side in each group was higher than that of the control and difference was significant in 10, 40 and 60 day groups (P < 0.05). This shows that the implant releases aluminium into the bone. Moreover, the calcium and phosphorus contents were significantly lower on the implanted side than on the control side in 10 and 20 day groups (P < 0.05-0.001). Apparently, the aluminium released from the implant in the early stage can interfere with the local calcium and phosphorus metabolism and delay the mineralization of the bone. PMID- 1288979 TI - New bone formation in the in vivo implantation of bioceramics. A quantitative analysis. AB - Two kinds of synthetic biomaterial, porous tricalcium phosphate (PTCP) and magnetic porous tricalcium phosphate (MPTCP) ceramic granules were implanted in rat femur. In the period of 4 months, the assessment of serial histological sections, scanning electron microphotographs and quantitative analysis of bone formation in the sections showed that both ceramics are biocompatible and degradable in vivo. More new bone formation occurred in the MPTCP group. Endochondral ossification was seen in both groups. The quantitative analysis in this study is reliable, and may be suitable to the similar experimental models. PMID- 1288980 TI - Carpal instability associated with fracture of the distal radius. Incidence, influencing factors and pathomechanics. AB - 134 fractures of the distal radius in 132 patients are reviewed to determine the incidence and influencing factors of coexisting carpal in stability. By measurement and analysis of the changes in carpal angles and joint spaces, carpal instability was discovered in 41 fractures, an incidence of 30.6%. Six patterns of instability were observed, including dorsal intercalated segmental instability (DISI), scapholunate dissociation, dorsal and palmar translocations, volar intercalated segmental instability (VISI) and ulnar carpal translocation. Accompanying carpal instability was more often seen in elderly patients. To a certain extent, the patterns of instability were related to the type of fracture and palmar tilt angle (PTA) values. DISI was often seen in fractures with PTA smaller than -15 degrees, while scapholunate dissociation was seen in fractures with PTA between -5 degrees and -20 degrees. The possible pathomechanics of the accompanying carpal instability were deduced based on the kinematics and influencing factors indicated in this study. PMID- 1288981 TI - Extraskeletal chondrosarcoma. Report of 8 cases. AB - Eight cases of surgically and pathologically verified extraskeletal (soft tissue) chondrosarcoma were analyzed with regard to clinical and X-ray features. Their cardinal clinical aspects included presence of a local soft tissue mass and gradual enlargement of the mass accompanied by increasing pain. The X-ray signs were formation of a soft tissue mass, various forms of calcification in the central area of the tumor presence of saucer-like defect on the cortical surface of neighbouring bone in some cases, and bending deformity of the affected bone. The incidence and sites of predilection, the main X-ray findings, radiological diagnosis and differential diagnosis of the tumor were discussed. PMID- 1288982 TI - Hepatic cavernous hemangioma. CT findings and pathological basis. AB - CT findings in 113 cases of hepatic hemangioma confirmed pathologically including 52 resected specimens and 8 autopsies were studied in correlation with the typical CT scan of 506 cases of the same disease. Mottling enhancement in the surrounding hepatic parenchyma of hemangioma which never appeared in other kinds of tumor was considered as a pathognomonic sign for diagnosis. It was correlated with the presence of dilated vascular spaces or sinusoids communicating with the tumor itself in the surrounding tissue. The thick wall and thin wall types of hemangioma were discussed. PMID- 1288983 TI - Tumoral calcium pyrophosphate dihydrate deposition disease. Report of a case with a review of the literature. AB - In a 56-year-old female patient with a mass at the proximal end of the left third finger for 22 years, the lesion enlarged obviously during the last 4 years. Initial diagnosis was chondroma with malignant change, and disarticulation of the finger was performed. Pathological diagnosis was "secondary chondrosarcoma". Microscopically, the mass contained a large amount of amorphous basophilic phosphate deposits surrounded by fibrous capsule. The pyrophosphate deposits consisted of birefringent needle shaped or rhomboid crystals which can be identified by polarizing microscope. It can be distinguished as tumoral calcium pyrophosphate dihydrate deposition disease, differing from tophaceous pseudogout, tumoral calcinosis and chondrocalcinosis. Nine cases were collected from the literature and the clinical, radiological and pathological features were discussed. PMID- 1288984 TI - Delivery by direct intrauterine transfer of gametes. AB - A nurse, 27, primary sterility for 5 years, had normal menstruation, normal size of uterus anterior. HSG: Rt. tube was not visible, Lt. tube slightly enlarged at ampulla. Ovaries were over-stimulated by clomiphene, HMG and hCG.8 ova were taken through vaginal aspiration under B-mode ultrasound scanning. Direct introduction of ova and washed sperms simultaneously into the uterus on Sept. 19, 1991 resulted in successful single pregnancy up to 36(+1) weeks. A 2 250 g normal baby boy was delivered on May 15, 1992 spontaneously. The base and prospect of this manoeuver are discussed with a reference to Craft's procedure. PMID- 1288985 TI - [Benign lymphadenosis of the oral mucosa: ultrastructural and immunopathological study]. PMID- 1288986 TI - [Chemosensitivity testing of adenocystic tongue and gingival cancer cell lines]. AB - Chemosensitivity testing of adenocystic, tongue and gingiva cancer cell lines to 14 antitumor drugs using a tetrazolium-based colorimetric assay (MTT assay) was carried out and the values of the relative antitumor activity (RAA) of the drugs were compared. Adriamycin (ADM), methotrexate (MTX) and fluorouracil (5-FU) showed the most potent RAA against the cell lines while Cantharidin (CTD) did not show RAA. The rank orders of other 10 drugs against each cell line differed from each another. PMID- 1288987 TI - [3-dimensional finite elements analysis in biomechanical study of cervical erosion of the tooth]. PMID- 1288988 TI - [The effect of founding condition on the microstructure of medium melting alloy]. AB - The effect of founding technology on the properties of medium melting alloy used in dentistry was studied. The porosity and inclusion for the new alloy as well as the cause and prevention of brittleness for the old alloy during remelting were investigated. By using of dehydration borax as purification agent during melting alloy was illustrated. PMID- 1288989 TI - [Functional appliance]. PMID- 1288990 TI - [Analysis of erroneous diagnosis on temporomandibular joint arthrography]. AB - In the present study, 433 arthrographic cases with temporomandibular joint dysfunction syndrome were included. 30 cases of them underwent operation and 22 cases underwent digital subtraction arthrographic examination after conventional arthrography. It has been found that arthrographic erroneous diagnosis could be made because the artificial manifestations caused by over-dose of contrast medium into the joint cavity, repeated puncture, anterior displacement of the condyle after injecting contrast medium and so on. In addition, the arthrographic manifestations of dis-clock were also analysed. PMID- 1288992 TI - [The relationship between family background and craniofacial morphology in class III malocclusions]. AB - Fifty five children with deciduous dentition and 36 adults were selected from 160 Class III patients, 40 children with normal occlusion used as cephalometric control group. T test was operated between the children with normal occlusion, Class III malocclusion with positive family background and with negative family background separately, and distinct analysis was carried out between the two Class III groups. Distribution of family background of skeletal Class III in children and in adults was chi 2 tested. Results show that craniofacial deformities of deciduous Class III malocclusion with positive family background are not more serious than those with negative one, and the rate of developing a skeletal class III malocclusion for patients with positive family background is not higher than those with negative one. It was implied that the value of family information collected by inquiring and cursorily examining the parents is limited for differential diagnosis between skeletal and functional class III malocclusion and it may mislead the prediction of treatment result in orthodontic clinic. PMID- 1288991 TI - [Gingival crevicular aspartate aminotransferase levels in periodontitis patients before and after periodontal treatment]. AB - Gingival crevicular fluid samples were collected from 296 teeth from 40 subjects, including 19 rapidly progressive periodontitis (RPP), 8 chronic adult periodontitis (CAP), 7 marginal gingivitis (MG) and 6 healthy subjects (H). The activities of aspartate aminotransferase (AST) in each sample were tested. The results were as follows: (1) The two groups with destructive periodontal disease (RPP and CAP) had greater GCF-AST levels than that from the two non-destructive groups (MG and H). (2) The GCF-AST activities showed significant positive correlations with clinical periodontal parameters, such as probing depth, attachment loss, bleeding index and suppuration. (3) Four weeks after thorough full-mouth root planing, both clinical parameters and GCF-AST levels decreased significantly. The present study suggests that GCF-AST activity might be a sensitive and objective marker for detection of periodontal tissue destruction and inflammation. PMID- 1288993 TI - [Repair of the extracranial facial nerve defect by autogenous vein graft: an experimental study]. AB - In this study, we repaired the extracranial facial nerve defect of rabbit using an autogenous vein graft and compared the results with conventional autogenous nerve graft in function and morphology. A 1 cm segment of the extracranial morphology. A 1 cm segment of the extracranial facial nerve was removed in 30 rabbits, the defect was repaired by a segment of vein or by a segment of nerve or without repair. The gross observation, histologic and histochemical examination, electrophysiological study and nerve fascicle graphics analysis were performed at 4, 8, 12, 20 weeks. The results of this study demonstrated that an autogenous vein as a non-nervous tissue graft can repair the extracranial facial nerve defect. 20 weeks after operation, the results with vein graft were superior to nerve graft. PMID- 1288994 TI - [The effect of gu chi wan on enzyme histochemistry changes in diabetic rats with experimental periodontal disease]. AB - This study observed the effect of Gu Chi Wan on the enzyme histochemistry changes of diabetic rats with experimental periodontal disease. The results indicate that the experimental group has not the decrease of oxidase-reductase and alkaline phosphatase as seen in control group and demonstrate the protective effect of Gu Chi Wan perhaps acts through regulating metabolism of periodontium of rats with experimental periodontal disease, and then improving the immune response of the host. PMID- 1288995 TI - [Immediate reconstruction of the maxillary with bone grafts supported by the buccal fat pad]. PMID- 1288996 TI - [Physiologic standard of selecting anterior teeth of the full denture]. PMID- 1288997 TI - [Clinical analysis of emergencies in endodontic treatment of teeth with necrotic pulps]. PMID- 1288998 TI - [A nutrition formula for adults with burn]. AB - The purpose of the present study was to develop a practical formula for calculating the necessary calorie value for Chinese adults with burns of different extents, and to verify the feasibility of the formula in patients with severe burns. 75 burned adults were entered for the study. Resting energy expenditure, some of the hormones and nutritional indices were assessed. On the basis of the observations on energy expenditure, and in accordance with the Chinese dietary tradition, the formula is established as follows: calorie value (kcal/day) = 1000 x body surface area (m2) + 25 x burned surface area (% TBSA); glucose: fat: protein = 55-60:20-30:15-20; calorie:nitrogen = 150-170:1. PMID- 1288999 TI - [Effect of surface cooling on free skin transplantation: experimental study and preliminary clinical application]. AB - Based on the fact that low temperature can reduce the oxygen consumption and metabolism of detached tissues, for preserving their viability before revascularization, we designed a computer-controlled surface cooling system, which can maintain a planned low temperature in the skin grafts, and the temperature recovers gradually with the revascularization of the grafts. The experiments on rabbits demonstrated that the temperature difference between the epidermic side and recipient-side was 6-8 degrees C when the surface cooling temperature was maintained at 20 degrees C. No significant adverse effects on the process of revascularization were observed. In three out of 4 patients, he flaps with subcutaneous fat reaching 7-9 mm. in thickness, survived. PMID- 1289000 TI - [Topical use of lysostaphin for Staphylococcus aureus infection of burn wounds in mice]. AB - The effect of lysostaphin on the burn wounds infected with Staphylococcus aureus was studied in mice. The results showed that the mortality and incidence of bacterial isolation in wounds were 17.2% and 8.3%, respectively, in mice treated by lysostaphin, and the figures were significantly lower than that treated by SD Ag (40.6% and 100%) or base (44.1% and 94.7%). In lysostaphin group the bacterial count of subeschar tissue was 1325 cfu/g, compared with more than 10(9) cfu/g in both SD-Ag and base groups. The results demonstrate that lysostaphin has powerful killing effect on S. aureus, and may be used as atopical antimicrobial to control burn wound infection with S. aureus. PMID- 1289001 TI - [In vitro measurement of antibacterial activities of topical antibacterial creams]. AB - A new method of in vitro measurement of antibacterial activity of different antimicrobial creams is introduced in this paper. The tested cream in known quantity is uniformed suspended in a solid medium, and bacteria of known quantity are inoculated. The result is expressed in MIC. In this observation, four creams were tested against 3 bacteria. It is the authors impression that the new method is better than the traditional disc method, as it reflects better the actual antibacterial activity of the drug in a cream base. It is helpful in selecting an effective drug or to evaluate the effectiveness of certain drugs in clinical practice. PMID- 1289002 TI - [Jump flap with pedicle containing superficial epigastric artery for treatment of exposed cranium after electric burn. Report of 9 cases]. AB - Nine patients with denuded cranium after electric burn were treated by using jump flaps with pedicle containing the superficial epigastric artery. The pedicle flap was first transplanted to the burned area on the wrist, and then retransplanted to the cranial defect. It was successful in all cases. The healing time was only one half of that for the traditional method consisting of multiple trephinings through the outer table and then autoskin grafting on the granulations. It also created a better ground for hair grafting later on. Comparing with free flaps or scalp flaps, it was easier to operate and more reliable in blood supply. PMID- 1289003 TI - [Autodermabrader in the early operation for deep second degree burns. A new operative mode in burns]. AB - Thirty-five cases of deep second burn of the hand (40 hands) were treated with autodermabrader to remove necrotic tissue. In comparison with 30 cases treated with tangential excision, bleeding was less and operation time was decreased markedly (P < 0.01) in the autodermabrader group. Histopathological study of the dermabrased wound was made to evaluate the mechanism of decreased bleeding. We consider that the new operative modality with autodermabader could be used in the treatment of deep II degree burn in exposed areas. PMID- 1289004 TI - [A new method of expanding free skin grafts]. AB - The harvested skin was processed by a skin-cutting-machine into strips of 0.3 or 0.5 cm in width. Then, the skin strips were glued on alternate folds of a pleated sheet of paper, each fold of which was 0.3 cm or 0.5 cm in width. The paper with skin strips on it was spread flat and cut across into 0.3 cm or 0.5 cm strips. These strips were again glued to another sheet of plicate paper. After being cut across again, many small blocks of skin in equidistance were finally obtained. They were then grafted on the recipient site. The area of grafted wound was four fold or more of the original area of the harvested skin. This method has been used in 6 patients with good result. PMID- 1289005 TI - [Management of stage III primary breast cancer. An analysis of 221 cases]. AB - From Jan. 1978 to Dec. 1987, 221 patients of stage III breast cancer were treated by surgery combined with adjuvant chemotherapy and/or radiation therapy. The overall 5-year survival rate was 50.4%. The 5-year survival rate in patients with negative lymph node was 72.3% as compared with 37.5% in patients with more than 7 lymph nodes involved (P < 0.05). In patients who received postoperative adjuvant chemotherapy, the 5-year survival rate in premenopausal or postmenopausal group was 62.1% and 41.4% respectively (P < 0.05). The regional lymph node recurrence rate was 4.0% in patients who received postoperative radiotherapy as opposed to 9.6% for those without radiotherapy postoperatively. The distant metastasis rate was 19.1% in lymph node negative group as compared with 45.9% in patients with more than 7 lymph nodes involved (P < 0.05). To decrease the distant metastasis will improve the survival rate in the treatment of breast cancer. We believe that preoperative chemotherapy combined with radical surgery and postoperative adjuvant therapy may improve the survival rate in stage III breast cancer. PMID- 1289006 TI - [Lymphatic metastasis of breast cancer and selection of operation]. AB - Studies of 169 cases of breast carcinoma showed that lymphatic metastasis was closely related to biological behavior of the cancer. Modified radical operation or modified extended radical operation were performed in cases of TNM stage I and II by pre- and intraoperative estimation of the tumor less than or about 5 cm in diameter, limited within mammary gland, and of expansion type. Histological typing and grading, degree of infiltration, condition of ER and lymphatic metastasis were used to plan postoperative adjuvant therapy. The importance of investigation of ER status of the lesions lies in proper arrangement of combined therapy and prediction of prognosis. PMID- 1289007 TI - [Infrared light scanning in differentiating benign and malignant breast diseases]. AB - One hundred and fifty patients with various breast diseases were studied using infrared light scanning. The results were compared with those of X-ray mammography and BUS. In 42 cases of breast cancer, 97% were correctly diagnosed using infrared light scanning. The method was significantly superior to X-ray (60%) and BUS (83%). To detect benign diseases, including adenofibromas (30 cases) and hyperplasias (21 cases), infrared light scanning was useful in this series in contrast to X-ray and BUS. PMID- 1289008 TI - [Doppler color flow imaging for demonstrating changes in portal hemodynamic after Hassab procedure]. AB - Doppler color flow imaging (DCFI) was used to observe portal hemodynamic changes in 40 patients with portal hypertension after Hassab procedure. Preoperative portal blood flow was hepatopetal in all patients, and in 30 of them gastric coronary vein was shown, with the hepatofugal blood flow of 235.32 +/- 56.24 ml/min, and the velocity of 8.62 +/- 2.33 cm/sec. Postoperatively, the gastric coronary vein was interrupted in 27 patients, the portal blood flow was significantly increased from 742.62 +/- 141.73 ml/min to 986.82 +/- 134.58 ml/min (P < 0.01) and the velocity was increased from 10.14 +/- 2.13 cm/sec to 13.41 +/- 1.91 cm/sec (P < 0.01). The results showed that the operation can stop abnormal blood flow in the gastrosplenic region and enhance liver perfusion. DCFI is useful for postoperative follow-up and observing portal hemodynamic changes. PMID- 1289009 TI - [Old spinal cord injury treated by pulsed electric stimulation]. AB - From March 1989 to May 1990, 80 cases of old spinal cord injury were treated with pulsed electric stimulation. The pulsed electric field was formed by utilizing paradural needle electrodes positioned cephalad and caudad to the site of spinal cord injury, with the stimulator connected with the electrodes being turned on. This stimulation was given 30 minutes once daily. 13 cases were treated for 3-6 months, 57 for 6-12 months, and 10 for 12-18 months. The nerve functions recovered in 78.5% of the cases (63/80), with the rate of useful recovery of 47.5% (38/80). The rate of EMG and gait improvement were 75.5% and 77.7%, respectively. The effect of pulsed electric stimulations was related to the extent of spinal cord injury, the depth and position of needle electrodes, the frequency and intensity of pulsed current and whether the spinal cord was compressed. PMID- 1289010 TI - [Congenital coronary artery-cardiac chamber fistula: diagnosis and surgical treatment]. AB - From Nov. 1976 to Dec. 1989, 9 patients with congenital coronary artery-cardial chamber fistula were operated upon in our hospital. In this series right coronary artery-right ventricle fistula was found in 3 patients, right coronary artery left ventricle fistula in 2, left coronary artery-right ventricle fistula in 2, left circumflex artery-right atrium fistula in 1, and bilateral coronary artery cardiac chamber fistula in 1. Cardiopulmonary bypass was performed in 8. The fistula was closed by interrupted mattress sutures outside the cardiac chamber plus ligation of terminal portion of the coronary artery near the fistula in 5 patients, and by mattress sutures inside the dilated coronary artery or cardiac chamber in other 4. There was no operative death in the 8 patients with single fistula. One patient with bilateral coronary artery fistula died from hypoxemia postoperatively. Late complications or recurrent fistulas were not found in the follow-up period from 3 months to 12 years. The diagnosis, operative indications and technique of closing fistula were discussed. PMID- 1289011 TI - [A stereoscopic localization apparatus for early diagnosis of lung cancer and its clinical application]. AB - We invented a stereoscopic localization apparatus for early diagnosis of lung cancer, facilitating fine needle aspiration biopsy especially for the deep situated small lesion of the lung. Under X-ray, the stereoscopic localization of the three dimensions, posteroanterior sagittal and frontal plane, and transverse section of the body with small lesions can be soon established accurately with the apparatus. 227 percutaneous aspiration biopsies of lung lesions were performed by using the apparatus from 1985 to 1989. Of the 206 patients, 180 had lung lesions less than 3cm in size, and in 89.6% of the patients positive diagnosis was obtained by the first puncture biopsy. Satisfactory specimens were obtained in 96.6% of the biopsies. 26 malignant lesions about 1cm in diameter were localized, punctured and diagnosed accurately. They were subsequently confirmed surgically and pathologically. Mild pneumothorax occurred in 19 patients, and it subsided spontaneously. PMID- 1289012 TI - [Surgical therapy of temporal lobe epilepsy. Clinical report of 30 cases]. AB - Resection of epileptic foci for the treatment of temporal lobe epilepsy was performed in 30 patients (19 right, 11 left). Spike epileptiform wave over the temporal region was found in all patients. All the resected specimen were studied by light and electron microscopy. The operative results showed that no epileptic attack recurred after discharge in 10 patients; seizures were controlled by drugs after 1-2 attacks in 12 patients; rare or occasional attacks in 6 patients; and no effect after operation in 2 patients. The effective rate was 93%, and no death and severe complications occurred. PMID- 1289014 TI - [The effects of electrical fields on neurons]. PMID- 1289013 TI - [Biomechanical and biological bases of the third type of fracture healing]. AB - Fracture healing may take place in the form of direct repair by laminar bone with a little callus, and it is called the third type of fracture healing or an optimal form of fracture healing. The results of stress analysis of electric measurements on the femoral shaft after osteotomy, which is fixed with plates, in simulation to load tests demonstrated that if the design of the plate is reasonable, even the load is added over twice of the body weight, the compression stress subjected to osteotomy site may be greater than that or nearly the same as that in the intact bone. In another animal experiment, a model of the third type of fracture healing of the canine tibial shaft osteotomy fixed with trapezoid compression plate (TCP) was established with polychromatic sequential labeling. The results of 3-point bending tests indicated that the strength and the rigidity of the healing bone may be greater than normal region. The mechanical and biological bases of the third type of fracture healing are provided by these experiments. PMID- 1289015 TI - Insulin antibody does not cause insulin resistance during glucose clamping in rats. AB - Although it has often been stated that insulin antibodies cause insulin resistance, this concept is still controversial. The effect of insulin antibody GP30, commonly used in insulin radioimmunoassay, on insulin action was investigated in Wistar rats in vivo by the euglycemic glucose clamp technique. As a preliminary experiment, the equilibrium time required for insulin antibody to bind with endogenous insulin was examined. One hundred microliters/kg insulin antibody took 60 min or more to attain equilibrium, but 10 microliters/kg insulin antibody almost immediately equilibrated with endogenous insulin. During a 60-min glucose clamp study, 2 mU/kg/min porcine insulin was infused with 100 microliters/kg insulin antibody. At steady state, during the last 20-min period, the mean glucose infusion rate was 2.10 +/- 0.85 mg/kg/min (n = 5, mean +/- SD), significantly lower than the 5.77 +/- 1.61 mg/kg/min of the control, indicating insulin resistance before equilibrium was reached. However, the glucose infusion rates during the clamp with 10 microliters/kg insulin antibody and 100 microliters/kg insulin antibody infused 75 min before the insulin were 6.10 +/- 1.44 and 7.12 +/- 1.19 mg/kg/min, respectively, no different from the control. In these instances, free insulin levels measured by radioimmunoassay using the polyethyleneglycol method were 43.8 +/- 20.4 and 15.4 +/- 6.1 microU/ml, respectively, lower than the control (77.0 +/- 16.1 microM/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289016 TI - Increased oxidized form of human serum albumin in patients with diabetes mellitus. AB - High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520H columns at neutral pH (6.87) showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are reduced and oxidized form of HSA, respectively. We studied the conversion of HMA to HNA (mercapt-nonmercapt conversion) as an index of oxidative change of the tissues and organs in 28 normal subjects and in a total of 47 patients with non-insulin dependent diabetes mellitus (NIDDM). Mean (+/- SD) values of the HMA fraction of HSA, f(HMA), [HMA/(HMA + HNA)], was significantly lower in NIDDM patients than in normal subjects (0.63 +/- 0.067 vs 0.75 +/- 0.028, P < 0.001). It was lower in poorly controlled NIDDM patients (0.63 +/- 0.058, n = 20) than in well controlled NIDDM patients (0.67 +/- 0.032, n = 9) (P < 0.05). Plasma glucose values sampled on occasions including overnight fasting and postprandial ones (r = -0.441, n = 47, P < 0.01), but not plasma glucose values sampled on overnight fasting (r = 0.345, n = 29) or postprandial (r = -0.467, n = 18) conditions and HbA1c (r = 0.211, n = 34), negatively correlated with the f(HMA) values, indicating that mercapt-nonmercapt conversion may not be due to cumulative hyperglycemia over a month, but due to short-term alteration in blood glucose level. The presence or absence of diabetic complications including nephropathy, retinopathy and neuropathy did not affect the f(HMA) values. In conclusion, decreased f(HMA) values in the diabetic patients suggested the presence of a rapidly altered oxidative change of albumin due to hyperglycemia. PMID- 1289017 TI - Similarity of the constituents between glomerular arteriolar and mesangial lesions in experimental diabetes. AB - In our previous studies in experimental diabetic rats, we have observed close similarities of ultrastructure and accumulation of IgG and IgM between the mesangial expansion and arteriolar hyalinosis of the glomerulus, and have presumed that both diabetic lesions are essentially of similar nature. In the present study, we carried out a further study on the constituents of both these lesions, using the PA-TCH-SP-PD technique for neutral carbohydrates, sialic acid and glycoproteins and the IgG-gold-silver technique for type IV collagen and fibronectin. The above staining and immunolabelings proved to be comparable in both lesions of diabetic glomerulopathies. This argues for the hypothesis of the identity of the two lesions. PMID- 1289018 TI - A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with type 1 (insulin-dependent) diabetes mellitus. AB - The contribution from lipoproteins, blood pressure, albuminuria and demographic variables to coronary heart disease in 90 adult subjects with and 172 without Type 1 diabetes mellitus was examined in order to investigate whether risk factors were of equivalent importance in diabetic and non-diabetic coronary heart disease. Coronary heart disease (CHD) was present in roughly 25% of subjects in each group. In Type 1 diabetes those with CHD had significantly higher levels of systolic blood pressure, albumin excretion, serum creatinine, triglycerides, VLDL cholesterol and C-peptide, and reductions in serum concentrations of HDL and HDL2 cholesterol, in comparison to those without. However, the prevalence of smokers, and concentrations of Lp(a), ApoB and fibrinogen were comparable. Blood pressure and HDL cholesterol were higher in the CHD group with Type 1 diabetes in comparison to the nondiabetic group with CHD, although LDL concentrations and the prevalence of Lp(a) concentrations > 200 mg/l were lower. Logistic regression analysis revealed the strongest independent predictors of CHD in Type 1 diabetes were serum triglycerides, systolic blood pressure, age, serum LDL cholesterol, and the daily insulin dosage, whereas in the non-diabetic control group HDL2 cholesterol, Lp(a), ApoA1 and ApoB, total serum cholesterol and body mass index were additional predictors. CHD in Type 1 diabetes appears to be most closely associated with increasing age and levels of blood pressure and total serum lipids. Apolipoproteins and albuminuria did not seem to be important independent predictors of CHD in Type 1 diabetes, whereas the former were more clearly associated with CHD in non-diabetic controls. PMID- 1289019 TI - Morning or bed-time insulin with or without glibenclamide in elderly type 2 diabetic patients unresponsive to oral antidiabetic agents. AB - We studied in a group of elderly (mean age 77 yr) non-obese Type 2 diabetic patients (n = 9) in a randomised, placebo-controlled prospective cross-over study of 8 months duration, the effects of substituting maximal sulfonylurea medication with a single injection of human zinc insulin taken either at bedtime (BTI) or morning (MI). All patients were poorly controlled with oral antidiabetic agents. After a 2-month regimen with either BTI or MI, a glibenclamide (GL, 3.5 mg/day) was given for an additional 2 months. Both insulin regimens decreased mean diurnal blood glucose and glycosylated HbA1c values to a similar extent (2.6 2.7%; p < 0.01-0.05), but with a lower daily insulin dose with BTI (0.30 +/- 0.03 IU/kg) as compared with MI (0.39 +/- 0.05 IU/kg; p < 0.01). A further improvement in metabolic control was observed in both groups after the introduction of GL; the mean reduction in glycosylated HbA1c was 1.4% for BTI and 0.7% for MI (p < 0.01 and 0.05, respectively), In conclusion, a subgroup of poorly controlled elderly Type 2 diabetic patients showed an improvement in metabolic control after a single injection of insulin despite discontinuation of maximal doses of oral antidiabetic agents. After 2 months of insulin treatment, a further improvement was achieved by a low dose of sulfonylurea in these patients who were formerly considered unresponsive to oral antidiabetic agents. PMID- 1289020 TI - Epidemiology of childhood diabetes in Osaka District, Japan, using the documents from the medical benefits system specific for childhood diabetes. AB - For an epidemiological study of childhood diabetes, application forms for medical benefits filed in Osaka Prefecture were collected and analyzed. A total of 465 patients with childhood diabetes under 18 yr of age were identified during the period between 1978 and 1988; 371 (175 boys and 196 girls) of them were classified as insulin-dependent diabetes mellitus (IDDM), and the others were either non-insulin-dependent diabetes mellitus (NIDDM) or an unidentified type of diabetes. The mean annual incidence of IDDM was 1.68 for boys and 2.00 for girls per 100,000 population, the rate being slightly higher for girls. The rates increased among older children, with a peak in the 10-14-yr age group. The prevalence estimated on the basis of the cumulative incidence in 1988 was 1.29 for boys and 1.60 for girls per 10,000 population, indicating a marked increasing trend with age. A significant seasonal variation was observed in the months of onset for IDDM, with higher rates during the winter. The mean birth weights of the male and female patients with IDDM were slightly lower than the national means. Use of official documents obtained from the medical benefits system was found to be an effective method for identification of cases of IDDM in the community, although further information is required for more accurate confirmation of such cases. PMID- 1289021 TI - Therapeutical concentrations of tolbutamide, glibenclamide, gliclazide and gliquidone at different glucose levels: in vitro effects on pancreatic A- and B cell function. AB - In the classical model of isolated perfused rat pancreas four commonly used sulfonylureas--tolbutamide, glibenclamide, gliquidone and gliclazide--were investigated at therapeutical concentrations at three different glucose levels (with 0, 2.22 and 5 mmol/l glucose surrounding) and in the presence of a metabolic stimulus with glucose at 8.33 mmol/l. All the sulfonylureas stimulated the B-cell function. Tolbutamide, gliquidone and gliclazide produced a prompt biphasic hormone release while glibenclamide induced a delayed monophasic insulin secretion. In all cases the amount of insulin released depended on the metabolic condition. As the environmental glucose levels fell, the sulfonylureas' stimulatory effect on the B-cell function decreased. At the therapeutical concentrations we tested, no sulfonylurea influenced A-cell activity whether directly or indirectly via an insulin-mediated paracrine inhibition of glucagon release. PMID- 1289023 TI - [Administration of metoprolol in refractory and severe heart failure]. AB - SUBJECTS: 46 cases of severe heart failure refractory to digitalis glycosides, diuretics and/or vasodilators were studied. TREATMENT: First dose of beta-loc (metoprolol) was 6.25 mg twice a day. If no untoward effects, according to patient's condition, the dose was gradually increased to 12.5-25 mg b.i.d. for 4 6 weeks. RESULTS: Of the total 46 cases, improvement was found in 44, among which 23 cases (50%) were excellent and 21 cases (46%) fine. The effective rate reached 96%, which was very satisfactory. PMID- 1289022 TI - Changes in urinary retinol binding protein excretion and other indices of renal tubular damage in patients with non-insulin dependent diabetes. AB - Changes in urine retinol binding protein (RBP, M(r) 21,000) excretion and other indices of renal tubular damage were investigated in the patients with non insulin dependent diabetes mellitus (NIDDM). Changes in urine RBP excretion were well paralleled with those of urine NAG excretion. In RBP-negative patients, the subjects with hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) showed higher beta 2-microglobulin (beta 2-MG) excretion and albumin (Alb)/Cr ratios than normotensive ones. In addition, both urine beta 2-MG excretions and Alb/Cr ratios were significantly increased in RBP positive patients. The measurement of urine RBP excretion may have an additional role in the diagnosis of renal tubular dysfunction in diabetic patients. PMID- 1289024 TI - [The effect of captopril on the immediate quality of life in patients with congestive heart failure]. PMID- 1289025 TI - [Hemodynamic studies on the effects of peruvoside on congestive heart failure]. PMID- 1289026 TI - [The effects of nitroglycerin on refractory congestive heart failure by intravenous infusion]. AB - Noninvasive hemodynamic and clinical studies were carried out in 24 patients with congestive heart failure refractory to digitalis, diuretics and vasodilators. Nitroglycerin was given by intravenous infusion for 5-7 days. The results showed that the symptoms, signs and hemodynamic parameters were markedly improved. The overall clinical effective rate was 96% and no serious side effect was noted. PMID- 1289027 TI - [Cardiopulmonary exercise test for evaluating cardiac reserve in chronic congestive heart failure]. AB - To evaluate whether maximal oxygen consumption (VO2 max) measured by cardiopulmonary exercise test (CAR-PET) reflects cardiac reserve in patients with congestive heart failure (CHF), supine bicycle CAR-PET and exercise hemodynamic measurements were performed simultaneously in 12 patients with CHF of NYHA II-IV. With increasing workload, VO2 and cardiac output elevated gradually, then plateaued, demonstrating that patients with CHF could reach VO2max. According to VO2max, patients were divided into 4 classes: including 2 patients of class A (VO2max: 24.5 +/- 2.29 ml.min-1/kg, mean +/- s mean), 3 of B (17.6 +/- 1.37 ml.min-1/kg), 5 of C (13.6 +/- 0.66 ml.min-1/kg) and 2 of D (6.5 +/- 1.64 ml.min 1/kg). Maximal cardiac indices were 8.79 +/- 2.35 L.min-1/m2 in class A, 5.82 +/- 0.97 L.min-1/m2 in B, 3.53 +/- 0.95 L.min-1/m2 in C and 2.21 +/- 1.56 L.min-1/m2 in D. No significant correlation between supine resting hemodynamic parameters and VO2max/kg was found, suggesting that exercise tolerance could not be predicted by the measurement of resting cardiac performance. Furthermore, VO2max correlated poorly with NYHA classification in these patients. However, cardiac output correlated linearly with VO2 during exercise, suggesting that VO2 max/kg is a good predictor for cardiac reserve in CHF(CI = 0.6809 +/- 0.2748 VO2/kg, n = 40, r = 0.84, P < 0.0001; CO = 1.1618 +/- 7.9065 VO2, n = 40, r = 0.84, P < 0.0001). The results also showed that VO2max/kg did not correlate with the changes of pulmonary capillary wedge pressure (PCWP), indicating that exercise tolerance in CHF depends more on cardiac output than on ventilatory consequence of pulmonary congestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289028 TI - [Catheter closure of patent ductus arteriosus without thoracotomy]. AB - Transcatheter plugging of patent ductus arteriosus with modified Porstmann's method was performed in children of school age and adults (130 cases) in recent 10 years. We devised a set of instrument, self-made plastic Ivalon for tailoring the plugs, developed the technique of retrograde aortic angiography to measure the diameter of the ductus, and determined the criteria of definite lodgement of the plug. 3 cases failed because their femoral arteries were too small to have the catheter sheath introduced. The other 3 cases developed thrombosis of the femoral arteries after the procedure, and the thrombi were removed by surgery. PMID- 1289029 TI - [Echocardiographic diagnosis and significance of atrial isomerism]. AB - Forty-nine patients with atrial isomerism (right atrial isomerism 27, left atrial isomerism 22) diagnosed by 2DE of the abdominal great vessels were reported in this paper. Compared with the results of high kilovolt filtered chest film and autopsy, atrial situs determined by 2DE was concordant with bronchial morphology in 43 patients, 25 (93%) of right atrial isomerism, 18 (82%) of left isomerism. 25 patients who had angiocardiography or autopsy were associated with other cardiac malformations which were severe and complicated in right atrial isomerism. The results of this series showed that ultrasonography of the abdominal great vessels could be a reliable guide to the diagnosis of atrial isomerism, 2DE diagnosis is useful for angiocardiography. PMID- 1289030 TI - [Entrainment phenomenon of atrioventricular nodal reentrant and atrioventricular reentrant tachycardias]. AB - Atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) were induced by esophageal pacing and their entrainment zones were examined in 20 patients. The results showed that the entrainment phenomenon, which was a common electrophysiological phenomenon in reentrant tachycardia, occurred during overdrive pacing in 19 cases (19/20). The entrainment zone was 10-70 (30.50 +/- 20.85, mean +/- s) ms. The tachycardias could not be interrupted by pacing within the entrainment zone, but they were terminated by burst pacing, with starting pacing cycle length shorter than the shortest entrainment cycle length. PMID- 1289031 TI - [A comparative study of the acute hemodynamic changes using a pacemaker at right atrium, atrioventricular junction and apex of the right ventricle]. PMID- 1289032 TI - [Evaluation of the effect of coronary angioplasty by exercise radionuclide myocardial perfusion tomography]. PMID- 1289033 TI - [The effect of radiofrequency ablation of canine atrioventricular junction on arrhythmias]. PMID- 1289034 TI - Does exceeding the MTD increase or decrease the cancer incidence in rodent studies? A testable hypothesis. PMID- 1289036 TI - Carl Paxson Sherwin, American pioneer in drug metabolism. PMID- 1289035 TI - Role of the gastrointestinal mucosa and microflora in the bioactivation of dietary and environmental mutagens or carcinogens. PMID- 1289037 TI - Inhalation anesthesia using physiologically based pharmacokinetic models. PMID- 1289038 TI - Mink as a predictive model in toxicology. AB - This paper reviewed the biomedical and toxicological database concerning the use of mink as a predictive model of human responses. It is concluded that substantial information exists on the mink genetics, physiology, metabolism, nutritional requirements, and susceptibility to infectious disease; and provides a foundation upon which interspecies extrapolation may be considered. In addition, information on the response of mink to several dozen toxic substances revealed that mink respond in a qualitatively and quantitatively similar manner to other more commonly employed species as well as humans. Our conclusion does not infer that mink should be used routinely in toxicological testing for estimation of human responses. However, it indicates that toxicological data from this species may be a useful complement in risk assessment processes based upon data obtained from traditionally employed models such as rats and dogs. PMID- 1289039 TI - [Comparative pathogenicity tests of eight pigeon paramyxovirus 1 variant isolates in pigeons, turkeys and chickens]. AB - Eight pigeon paramyxovirus-1 isolates which were isolated from diseased pigeons were comparatively tested for their pathogenicity in chickens, turkeys and racing pigeons. Intramuscular inoculation of all of the eight viruses resulted in all pigeons in clinical signs like polyuria, lameness of wings and in parts also in torticollis. Also, intravenously inoculated chickens developed distinct signs such as apathy, liquid droppings and in part also torticollis. Six of the eight PMV-1 isolates induced in turkeys similar signs as in chickens; inoculation of two isolates yielded no signs in turkeys. Legal sanitary consequences of the disease due to pigeon PMV-1 infection in chickens and in turkeys should be identical to that of velogenic Newcastle disease. PMID- 1289040 TI - [The aerobic bacterial flora of songbird nests]. AB - In the area around Ober- and Unterschleissheim, a medium term decrease in the singing bird population appears to be happening. Therefore, material from nesting boxes (used for nesting or sleeping) was examined for bacterial contamination. Mainly gram positive bacteria were isolated which were considered to belong to the normal flora. The occurrence of Streptomyces spp. is described in the nesting material of Passeres probably for the first time. Enterobacteriaceae represent only a fraction of the total isolates, but are demonstrated relatively frequently in the nests of the Nuthatch (Sitta europaea) and nests of other non-identified bird spp., so that colonization of the intestinal tract with Enterobacteriaceae cannot be excluded. Surprisingly, bacteria of the aquatic habitats such as Alcaligenes, Bordetella, Aeromonas, Non-Cholera (NC)-Vibrio were isolated, although in small amounts. The occurrence of NC-Vibrio has not yet been described in singing birds. Nests with high numbers of gram negative rods were successful in most instances, therefore, there was no proof that aerobic bacteria are responsible for the decrease in the population. PMID- 1289042 TI - Comparative investigation on different turkey rhinotracheitis (TRT) virus isolates from different countries. AB - The present investigation was carried out to compare the antigenic relationship between TRT virus isolates from different countries. The obtained results showed that all virus isolates shared similar physiochemical properties. In virus neutralisation tests marked two way cross reactions between BUT 1 = 8544 (England), STG 761/88 and STG 854/88 (Germany) could be detected. On the other hand VCO 3 isolate (France) showed only partial reaction. Also the SDS-poly acrylamide gel electrophoresis (SDS-PAGE) profiles of three TRT viruses (one from England and two from Germany) were very similar, while the VCO 3 strain from France showed some variation. PMID- 1289041 TI - [Immunizing against salmonella infections with live and inactivated vaccines]. AB - A live attenuated auxotrophic S. typhimurium (S. tm.)-mutant was used by orally administration via drinking water several times during rearing, combined with 1- or 2-times parenteral injection of an autogenous S. enteritidis (S. e.)/S. tm. oil emulsion vaccine. In a 8-month period, more than 500,000 birds were vaccinated. The vaccine was safe. Challenge test showed protection in the vaccinates and their offspring. The number of isolates in the farms detected by regular monitoring decreased. The protection of the live-culture mutant lasted about only 8 to 10 weeks. A. S. tm.-mutant more potent for chickens will be tested now. We consider vaccinations as one important factor in a salmonella control program, especially for commercial layers and broiler breeders. PMID- 1289043 TI - Effect of sample selection from experimentally contaminated hatching eggs and freshly hatched chicks on Salmonella enteritidis detection rate. AB - The conventional culture methods of hatching eggs using shell and/or egg contents for detection of salmonella organisms give mostly unsatisfactory results. The aim of the present study is to evaluate selection of other samples and techniques of culturing hatching eggs and freshly hatched chicks. This current study provides the best evidence of Salmonella enteritidis in artificially contaminated eggs (Layer type) by using enrichment broth in empty egg shell samples in comparison to culturing samples from yolk, albumen or from shell above the air cell (with the outer shell membrane). The isolation rates could be enhanced if empty egg shell was initially filled with Buffered Pepton Water as pre-enrichment broth. Examination of organs from freshly hatched chicks revealed that crop samples give mostly higher reisolation rates. PMID- 1289044 TI - [The survival ability of salmonella, coccidia oocysts and ascarid eggs in laying hen feces from different housing systems]. AB - The time of survival of Salmonella typhimurium, coccidia oocysts and ascaris eggs in manure of layer was determined in 5 different housing systems and 2 storing places for litter. The experiments were carried out in a stable of experimental station Frankenforst of the university of Bonn with a flock of 2200 hens. The effects of the environment conditions temperature, dry matter content, pH-value and intestinal microflora of the manure have also been studied. The time of survival was different depending on the housing system. A recovery of viable coccidia oocysts was possible after 13-370 days, ascaris eggs 53-347 days and Salmonella typhimurium 2-175 days. The tenacity of the investigated test organism mainly depend on the dry matter content of the manure. The longest period of survival of salmonellas was found in dry environment conditions, were as coccidia oocysts and ascaris eggs have been observed with the shortest period of survival. The possibility of the examined resistant parasite stages to develop was disturbed. Only few of them were able to develop and with a longer development time than those examined in the control suspension. The results of this study indicate that chicken manure, before using it in plant production, should be stored long enough to prevent men or animals from possible infections. PMID- 1289045 TI - [The tenacity of Newcastle disease virus (LaSota) in the excrement of laying hens in different housing systems]. AB - The survival time of NDV (LaSota) in the excrement of layers was in summer (winter) 22 and 18 days (26 and 36 days) in two cage houses, 14 and 18 days (36 and 33 days) in two floor-pen houses, as well as 8 days (54 and 68 days) in two dropping store places. By one week staying in battery cages and following the storage in dropping store place after 47 or 50 days NDV (LaSota) could not be reisolated. Besides environment factors, temperature, pH and dry matter was the thermic effect very significant. The comparison of the tenacity of NDV (LaSota) in different housing systems was besides of the quantitative determination of survival time supported through the application of a life time distribution test. PMID- 1289046 TI - [Flock data reported from a poultry slaughter house (broilers)]. AB - Six broiler flocks have been compared with regard to the occurrence of attributes according to an examination protocol. Approved birds were scrutinized per random sample, condemned birds altogether. Parameters of examination were body weight occurring attributes (computed single and cumulated) count of dead and condemned birds in fattening period, transport and on slaughter line as well. Each flock was conspicuous in one or another respect. The graduation of the flocks was possible using the factors losses in the fattening period count of condemnation losses in the total production line coefficient of variation of weights attributes occurring in the meat inspection cumulated count of all attributes leading to condemnation. Results demonstrate, that graduation of different flocks by means of quantitative measurements is possible. PMID- 1289047 TI - [Nitrogen and chemical oxygen demand burden of waste water caused by trout raising influenced by the protein content of the feed]. AB - A possibility was shown, how to quantify the water content of nitrogen and COD (Chemical Oxygen Demand) from intensive fish production, independent of flow rate and feeding time. The nitrogen excretion could be reduced 50% by feeding a protein reduced fish feed (A: 38.4% XP) compared with an fish feed B contending 47.9% protein (XP). The excretion-compartments were evaluated with the waste water parameter COD. Doing this, it could be shown that the COD input by feed A is reduced 20% in opposite to feed B. Further more the separation of fish faeces would achieve an COD reduction from about 50% to 70%. PMID- 1289048 TI - [A model trial for prophylaxis in intensive fish culture]. AB - Prophylactic measures concerning stock management, premises (indoor systems), water supply (tap water as make-up water in reuse systems), water quality control and management, fish feed and staff (short term quarantine after contact with other fish or equipment) helped to build up and maintain a disease free stock of rainbow trout (Oncorhychus mykiss) over a period of seven years in a time-limited trial. 60% of fertilized eggs survived, 3 fish were lost out of 1000 reared to pan-size without any medication. Although it must be kept in mind that the trial was a small size undertaking it can be shown that consequent prophylactic measures can prevent disease mediated losses of fish. PMID- 1289049 TI - [The significance of the weaning age of young rabbits for the development of young animals and their food consumption]. AB - The experiment reported compared the influence of weaning at 25, 28, 31 and 35 days of age on the development of liveweight and food consumption during the pre- and post-weaning period hybrid rabbits. Results of 44 does and 949 offspring showed that late weaning exerted a positive influence on live-weight development in comparison with already weaned kits of the same age. In all weaning age groups a depression in growth occurred shortly after weaning which was compensated thereafter. There was no significant difference between treatments with regard to total food consumption of does and offspring. This lack of difference was due to the high food intake of lactating does after weaning that surpassed maintenance requirements. PMID- 1289050 TI - [Injection technique and arthrography of the shoulder, elbow and carpal joints of the cat]. AB - Nine cats were available for the present trial. Six thoracic limbs were dissected without any previous treatment. In the remaining twelve thoracic limbs, each articular space was injected with silicone and then fixed with a 5% formalin solution before being submitted to dissection. For the radiological examination ten adult cats were available and arthrographs were taken in two axial planes of each joint. The elbow-joints of six additional cats were injected with six differently formulated contrast media. Radiographs were taken at different time intervals: instantly, five and ten minutes after intraarticular injection. The quality of the contrast and clarity of the structures are discussed. A lateral and a cranial location for injection are described for shoulder-joint, as well as a caudolateral and a craniolateral location for the elbow. A dorsal injection location is recommended for the antebrachiocarpal articulation and the middle carpal articulation. The injection sides described are discussed comparing them with those taken from the literature on dogs and cats. The results obtained from arthrograms are compared with data from literature on dogs. The radiographs of the elbow show clear differences in quality depending on the contrast medium used and on time between injection and exposure. As a result, recommendations can be made for suitable contrast media for arthrograms of the shoulder-, elbow- and carpal-joint in cats. Further, it is recommended that radiographs should be taken not later than five minutes after injection of the contrast media. PMID- 1289051 TI - [The arthrographic presentation of the hip, knee and tarsal joints of the cat]. AB - The purpose of the present paper was to find out the most suitable localizations to puncture of hip, stifle and hock joints of the domestic cat. These joints are arthrographically presented. Further six contrast mediums in normal commercial usage were tested with regard to there contrast intensity. The only recommendable localization to arthrocentesis of the hip joint is at the cranial border of the greater trochanter of the femur. The stifle joint is approachable either at the medial or lateral border of the Lig. patellae. To puncture the proximal row of the hock joint the recommendable puncture site was found distal of the lateral malleolus between the tendons of the lateral digital extensor muscle and m. extensor digitorum longus. Any arthrocentesis of the distal row of the hock joint isn't recommendable. Contrast mediums with a iodine concentration below 300 mg/ml were not sufficient for arthrography. PMID- 1289052 TI - Cranial and trunk neural crest cells use different mechanisms for attachment to extracellular matrices. AB - We have used a quantitative cell attachment assay to compare the interactions of cranial and trunk neural crest cells with the extracellular matrix (ECM) molecules fibronectin, laminin and collagen types I and IV. Antibodies to the beta 1 subunit of integrin inhibited attachment under all conditions tested, suggesting that integrins mediate neural crest cell interactions with these ECM molecules. The HNK-1 antibody against a surface carbohydrate epitope under certain conditions inhibited both cranial and trunk neural crest cell attachment to laminin, but not to fibronectin. An antiserum to alpha 1 intergrin inhibited attachment of trunk, but not cranial, neural crest cells to laminin and collagen type I, though interactions with fibronectin or collagen type IV were unaffected. The surface properties of trunk and cranial neural crest cells differed in several ways. First, trunk neural crest cells attached to collagen types I and IV, but cranial neural crest cells did not. Second, their divalent cation requirements for attachment to ECM molecules differed. For fibronectin substrata, trunk neural crest cells required divalent cations for attachment, whereas cranial neural crest cells bound in the absence of divalent cations. However, cranial neural crest cells lost this cation-independent attachment after a few days of culture. For laminin substrata, trunk cells used two integrins, one divalent cation-dependent and the other divalent cation-independent (Lallier, T. E. and Bronner-Fraser, M. (1991) Development 113, 1069-1081). In contrast, cranial neural crest cells attached to laminin using a single, divalent cation dependent receptor system. Immunoprecipitations and immunoblots of surface labelled neural crest cells with HNK-1, alpha 1 integrin and beta 1 integrin antibodies suggest that cranial and trunk neural crest cells possess biochemically distinct integrins. Our results demonstrate that cranial and trunk cells differ in their mechanisms of adhesion to selected ECM components, suggesting that they are non-overlapping populations of cells with regard to their adhesive properties. PMID- 1289053 TI - Differential screening of a PCR-generated mouse embryo cDNA library: glucose transporters are differentially expressed in early postimplantation mouse embryos. AB - Differential screening of a cDNA library constructed using PCR amplification techniques from RNA isolated from the distal portion (embryonic ectoderm, mesoderm and visceral endoderm) of 7.5 days post coitum (dpc) mouse embryos led to the isolation of two cDNA clones expressed at higher levels in 7.5 dpc embryos than 12.5 dpc embryos. Nucleotide sequence analysis revealed that each of these clones was a different member of the family of facilitative glucose transporters (Glut genes). The differentially expressed cDNA clones represent mouse Glut-1 and Glut-3. Levels of the Glut-3 mRNA declined 14-fold between days 7.5 and 12.5 of gestation, and were under our limits of detection by 14.5 dpc. The levels of the Glut-1 mRNA declined about 3-fold between days 7.5 and 12.5 of gestation. Analysis of the expression of these genes by in situ hybridization revealed striking differences in transcript localization in early postimplantation mouse embryos. At 7.5 dpc, both transporters were expressed more strongly in extraembryonic tissues than in the embryo proper. While both transporters were expressed in the amnion and chorion, only Glut-1 was expressed in the ectoplacental cone. In the yolk sac, Glut-3 appeared to be expressed only in the endoderm while Glut-1, although expressed in both layers, was expressed more strongly in the mesoderm layer. Thus, the two transporters have relatively reciprocal sites of expression in the developing extraembryonic membranes. Expression of Glut-1 was fairly widespread in the embryo at 8.5 dpc, but by 10.5 dpc expression was down-regulated and was observed in the eye and the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289054 TI - Restoration of hair growth by surgical implantation of follicular dermal sheath. AB - The capacity of lower follicle dermal sheath to restore hair growth was tested by removing the lower halves of follicles, and then immediately implanting material containing dermal sheath cells from these bases, into the remaining upper epidermal follicle cavity. Over 60% of recipient follicles produced stout emergent vibrissa fibres and some operations resulted in multiple hair production from a single follicle. Histological examination revealed new dermal papillae within large bulb structures which were sited below the level of amputation--a feature that indicated that the new dermal papilla was derived from implanted material. For many follicles, the failure to produce emergent fibres could be accounted for after histological examination. These results provide clear evidence that lower follicle dermal sheath cells are capable of replacing those of the dermal papilla and it shows that they can do so in the context of the upper follicle. However, because elements of lower follicle epidermis were present in the implant material, the interactive sequence of events cannot be established. Dermal sheath cells have immense potential for papilla cell replacement: questions remain as to whether the distinction between sheath and papilla cells is one of context, or whether the transition requires specific external influences. PMID- 1289056 TI - The expression of tissue and urokinase-type plasminogen activators in neural development suggests different modes of proteolytic involvement in neuronal growth. AB - Tissue and urokinase-type plasminogen activators are serine proteases with highly restricted specificity, their best characterised role being to release the broad specificity protease plasmin from inactive plasminogen. It has frequently been suggested that these, and similar proteases, are involved in axonal growth and tissue remodelling associated with neural development. To help define what this role might be, we have studied the expression of the plasminogen activators in developing rat nervous tissue. Urokinase-type plasminogen activator mRNA is strongly expressed by many classes of neurons in peripheral and central nervous system. We have analysed its appearance in spinal cord and sensory ganglia, and found the mRNA is detectable by in situ hybridisation very early in neuronal development (by embryonic day 12.5), at a stage compatible with it playing a role in axonal or dendritic growth. Tissue plasminogen activator mRNA, on the other hand, is expressed only by cells of the floor plate in the developing nervous system, from embryonic day 10.5 and thereafter. Immunohistochemical and enzymatic analysis showed that active tissue plasminogen activator is produced by, and retained within, the floor plate. A mechanism is suggested by which high levels of tissue plasminogen activator produced by the stationary cells of the floor plate could influence the direction of growth of commissural axons as they pass through this midline structure. PMID- 1289055 TI - Expression of Pax-3- and neuroectoderm-inducing activities during differentiation of P19 embryonal carcinoma cells. AB - A P19 embryonal carcinoma stem cell line carrying an insertion of the E. coli LacZ gene in an endogenous copy of the Pax-3 gene was identified. Expression of the Pax-3/LacZ fusion gene in neuroectodermal and mesodermal lineages following induction of differentiation by chemical treatments (retinoic acid and dimethylsulfoxide) was characterized using this line and is consistent with the previous localization of Pax-3 expression in the embryo to mitotically active cells of the dorsal neuroectoderm and the adjacent segmented dermomyotome. Pax 3/LacZ marked stem cells were also utilized as target cells in mixing experiments with unmarked P19 cells that had been differentiated by pretreatment with chemical inducers. Induction of beta-galactosidase and neuroectodermal markers in the target cells demonstrates that: (1) some differentiated P19 cell derivatives transiently express endogenous Pax-3- and neuroectoderm-inducing activities, (2) undifferentiated target stem cells respond to these activities even in the presence of leukemia inhibitory factor and (3) the endogenous activities can be distinguished from, and are more potent than, retinoic acid treatment in inducing neuroectoderm. These observations demonstrate that P19 embryonal carcinoma cells provide a useful in vitro system for analysis of the cellular interactions responsible for neuroectoderm induction in mammals. PMID- 1289057 TI - Multiple gap junction genes are utilized during rat skin and hair development. AB - The expression of four different gap junction gene products (alpha 1, beta 1, beta 2, and beta 3) has been analysed during rat skin development and the hair growth cycle. Both alpha 1 (Cx43) and beta 2 (Cx26) connexins were coexpressed in the undifferentiated epidermis. A specific, developmentally regulated elimination of beta 2 expression was observed in the periderm at E16. Coinciding with the differentiation of the epidermis, differential expression of alpha 1 and beta 2 connexins was observed in the newly formed epidermal layers. alpha 1 connexin was expressed in the basal and spinous layers, while beta 2 was confined to the differentiated spinous and granular layers. Large gap junctions were present in the basal layer, while small gap junctions, associated with many desmosomes, were typical for the differentiated layers. Although the distribution pattern for alpha 1 and beta 2 expression remained the same in the neonatal and postnatal epidermis, the RNA and protein levels decreased markedly following birth. Hair follicle development was marked by expression of alpha 1 connexin in hair germs at E16. Following beta 2 detection at E20, the expression increased for both alpha 1 and beta 2 in developing follicles. A cell-type-specific expression was detected in the outer root sheath, in the matrix, in the matrix-derived cells (inner root sheath, cortex and medulla) and in the dermal papilla. In addition, alpha 1 was specifically expressed in the arrector pili muscle, while sebocytes expressed both alpha 1 and beta 3 (Cx31) connexin. beta 1 connexin (Cx32) was not detected at any stage analysed. The results indicate that multiple gap junction genes contribute to epidermal and follicular morphogenesis. Moreover, based on the utilization of gap junctions in all living cells of the surface epidermis, it appears that the epidermis may behave as a large communication compartment that may be coupled functionally to epidermal appendages (hair follicles and sebaceous glands) via gap junctional pathways. PMID- 1289059 TI - Commitment along the dorsoventral axis of the sea urchin embryo is altered in response to NiCl2. AB - Few treatments are known that perturb the dorsoventral axis of the sea urchin embryo. We report here that the dorsoventral polarity of the sea urchin embryo can be disrupted by treatment of embryos with NiCl2. Lytechinus variegatus embryos treated with 0.5 mM NiCl2 from fertilization until the early gastrula stage appear morphologically normal until the midgastrula stage, when they fail to acquire the overt dorsoventral polarity characteristic of untreated siblings. The ectoderm of normal embryos possesses two ventrolateral thickenings just above the vegetal plate region. In nickel-treated embryos, these become expanded as a circumferential belt around the vegetal plate. The ectoderm just ventral to the animal pole normally invaginates to form a stomodeum, which then fuses with the tip of the archenteron to produce the mouth. In nickel-treated embryos, the stomodeal invagination is expanded to become a circumferential constriction, and it eventually pinches off as the tip of the archenteron fuses with it to produce a mouth. Primary mesenchyme cells form a ring in the lateral ectoderm, but as many as a dozen spicule rudiments can form in a radial pattern. Dorsoventral differentiation of ectodermal tissues is profoundly perturbed: nickel-treated embryos underexpress transcripts of the dorsal (aboral) gene LvS1, they overexpress the ventral (oral) ectodermal gene product, EctoV, and the ciliated band is shifted to the vegetal margin of the embryo. Although some dorsoventral abnormalities are observed, animal-vegetal differentiation of the archenteron and associated structures seems largely normal, based on the localization of region specific gene products. Gross differentiation of primary mesenchyme cells seems unaffected, since nickel-treated embryos possess the normal number of these cells. Furthermore, when all primary mesenchyme cells are removed from nickel treated embryos, some secondary mesenchyme cells undergo the process of "conversion" (Ettensohn, C. A. and McClay, D. R. (1988) Dev. Biol. 125, 396-409), migrating to sites where the larval skeleton would ordinarily form and subsequently producing spicule rudiments. However, the skeletal pattern formed by the converted cells is completely radialized. Our data suggest that a major effect of NiCl2 is to alter commitment of ectodermal cells along the dorsoventral axis. Among the consequences appears to be a disruption of pattern formation by mesenchyme cells. PMID- 1289058 TI - Expression of the genes for TGF alpha, EGF and the EGF receptor during early pig development. AB - Expression of mRNA for transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF) and the epidermal growth factor receptor (EGF-R) during early pig development was evaluated by reverse transcription-PCR. In the unfertilised pig oocyte, maternal transcripts for EGF, but not for TGF alpha or the EGF-R, were detected. Pig conceptuses were analysed at days 7, 8, 10, 12, 15, 17, 18 and 22 of pregnancy. EGF-R mRNA was detected at all stages of conceptus development analysed. Interestingly, TGF alpha mRNA was expressed by the developing blastocyst only at days 8, 10 and 12 of pregnancy, with the highest levels apparent at day 10. In contrast, EGF mRNA was first expressed by the post elongation conceptus at around day 15 of pregnancy with levels continuing to increase up to day 22. In the day-18 and day-22 conceptuses, this EGF message was shown to be primarily a product of the embryo-amnion and not the placental membranes. Furthermore, EGF was immunolocalised in the day-22 embryo to the developing lung bud, gut loop and amnion. In summary, the expression pattern of TGF alpha mRNA during early pig development is coincident with the onset of blastocyst elongation and suggests a possible role for TGF alpha during this period of cellular remodelling. The temporal and spatial expression of EGF mRNA and protein suggests a possible involvement for EGF in the establishment of the early organ systems. PMID- 1289060 TI - An X-linked human collagen transgene escapes X inactivation in a subset of cells. AB - Transgenic mice carrying one complete copy of the human alpha 1(I) collagen gene on the X chromosome (HucII mice) were used to study the effect of X inactivation on transgene expression. By chromosomal in situ hybridization, the transgene was mapped to the D/E region close to the Xce locus, which is the controlling element. Quantitative RNA analyses indicated that transgene expression in homozygous and heterozygous females was about 125% and 62%, respectively, of the level found in hemizygous males. Also, females with Searle's translocation carrying the transgene on the inactive X chromosome (Xi) expressed about 18% transgene RNA when compared to hemizygous males. These results were consistent with the transgene being subject to but partially escaping from X inactivation. Two lines of evidence indicated that the transgene escaped X inactivation or was reactivated in a small subset of cells rather than being expressed at a lower level from the Xi in all cells, (i) None of nine single cell clones carrying the transgene on the Xi transcribed transgene RNA. In these clones the transgene was highly methylated in contrast to clones carrying the transgene on the Xa. (ii) In situ hybridization to RNA of cultured cells revealed that about 3% of uncloned cells with the transgene on the Xi expressed transgene RNA at a level comparable to that on the Xa. Our results indicate that the autosomal human collagen gene integrated on the mouse X chromosome is susceptible to X inactivation. Inactivation is, however, not complete as a subset of cells carrying the transgene on Xi expresses the transgene at a level comparable to that when carried on Xa. PMID- 1289061 TI - The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. AB - The segment polarity gene wingless has an essential function in cell-to-cell communication during various stages of Drosophila development. The wingless gene encodes a secreted protein that affects gene expression in surrounding cells but does not spread far from the cells where it is made. In larvae, wingless is necessary to generate naked cuticle in a restricted part of each segment. To test whether the local accumulation of wingless is essential for its function, we made transgenic flies that express wingless under the control of a hsp70 promoter (HS wg flies). Uniform wingless expression results in a complete naked cuticle, uniform armadillo accumulation and broadening of the engrailed domain. The expression patterns of patched, cubitus interruptus Dominant and Ultrabithorax follow the change in engrailed. The phenotype of heatshocked HS-wg embryos resembles the segment polarity mutant naked, suggesting that embryos that overexpress wingless or lack the naked gene enter similar developmental pathways. The ubiquitous effects of ectopic wingless expression may indicate that most cells in the embryo can receive and interpret the wingless signal. For the development of the wild-type pattern, it is required that wingless is expressed in a subset of these cells. PMID- 1289062 TI - A new member of the spectrin superfamily may participate in the formation of embryonic muscle attachments in Drosophila. AB - Myotube migration and the formation of muscle attachments are crucial events for the proper development of muscle patterning in the Drosophila embryo. This paper describes the identification of a new embryonic muscle-specific protein, MSP-300, in Drosophila. This protein is initially expressed by muscle precursors at muscle ectoderm and muscle-muscle attachment sites. As development continues, MSP-300 becomes associated with muscle myofibrillar network. Studies of the subcellular localization of this muscle-specific protein in primary embryonic cultured myotubes show that MSP-300 decorates actin filaments, and that it is specifically enriched in sites where actin microfilaments are linked to the plasma membrane. Migrating myotubes exhibit high levels of this protein at their leading edge while, in myotubes that have already developed sarcomeric architecture, the protein is localized mainly at the Z-discs. Sequence of a partial 3.9 kb cDNA clone and molecular analysis of the predicted protein sequence of this protein indicates that it encodes a high relative molecular mass protein (approximately 300 x 10(3), which exhibits at least five spectrin-like repeats. Several properties are shared by MSP-300 and members of the spectrin superfamily: it is associated with actin microfilaments, its sequence exhibits spectrin-like repeats and it is localized at sites where actin is linked to the plasma membrane. This protein could have a developmental role in the formation of muscle-ectoderm attachments and may be involved in myotube migration on the ectoderm. PMID- 1289063 TI - Multiple cholinergic differentiation factors are present in footpad extracts: comparison with known cholinergic factors. AB - Sweat glands in rat footpads contain a neuronal differentiation activity that switches the phenotype of sympathetic neurons from noradrenergic to cholinergic during normal development in vivo. Extracts of developing and adult sweat glands induce changes in neurotransmitter properties in cultured sympathetic neurons that mimic those observed in vivo. We have characterized further the factors present in the extract and compared their properties to those of known cholinergic factors. When assayed on cultured rat sympathetic neurons, the major activities in footpad extracts from postnatal day 21 rat pups that induce choline acetyltransferase (ChAT) and vasoactive intestinal peptide (VIP) and reduce catecholamines and neuropeptide Y (NPY) are associated with a soluble protein of 22-26 x 10(3) M(r) and a pI of 5.0. These properties are similar to those of ciliary neurotrophic factor (CNTF). Moreover, the purified fraction from footpads has ciliary neurotrophic activity. Antibodies to CNTF that immunoprecipitate all differentiation activity from sciatic nerve extracts, a rich source of CNTF, immunoprecipitate 80% of the cholinergic activity in the footpad extracts, 50% of the VIP and 20% of the NPY activities. Neither CNTF protein nor CNTF mRNA, however, can be detected in immunoblot and northern analysis of footpads even though both CNTF protein and mRNA are evident in sciatic nerve. CNTF immunoreactivity is associated with a sparse plexus of sensory fibers in the footpad but not with sweat glands or the Schwann cells associated with them. In addition, in situ hybridization studies with oligonucleotide probes failed to reveal CNTF mRNA in sweat glands. Comparison of the sweat gland differentiation activity with the cholinergic differentiation factor from heart cells (CDF; also known as leukemia inhibitory factor or LIF) suggests that most of the cholinergic activity in foot pads is biochemically distinct from CDF/LIF. Further, antibodies that block the activity of CDF/LIF purified from heart-cell-conditioned medium do not block the ChAT-inducing activity present in footpad extracts of postnatal day 8 animals. A differentiation factor isolated from skeletal muscle did not induce cholinergic properties in sympathetic neuron cultures and therefore is unlikely to be the cholinergic differentiation factor produced by sweat glands. Taken together, our data suggest that there are at least two differentiation molecules present in the extracts and that the major cholinergic activity obtained from footpads is related to, but distinct from, CNTF. The second factor remains to be characterized. In addition, CNTF associated with sensory fibers may make a minor contribution to the cholinergic inducing activity present in the extract. PMID- 1289064 TI - Characterization of a germ-line proliferation mutation in C. elegans. AB - The C. elegans germ line is generated by extensive proliferation of the two germ line progenitor cells present in newly hatched larvae. We describe genetic and phenotypic characterization of glp-4, a locus whose product is required for normal proliferation of the germ line. glp-4(bn2ts) mutant worms raised at the restrictive temperature contain approximately 12 germ nuclei, in contrast to the 700-1000 present in wild-type adults. The few germ cells present in sterile glp-4 adults appear to be arrested at prophase of the mitotic cell cycle. This cell cycle disruption prevents the germ cells from entering meiosis and differentiating into gametes. Shifting sterile glp-4 worms to the permissive temperature enables their germ cells to undergo extensive proliferation and form gametes, demonstrating that the bn2-induced cell-cycle arrest is reversible and that proliferation and differentiation of germ cells can be uncoupled from development of the somatic gonad. The glp-4(bn2ts) mutation can be used to generate large populations of worms that are severely depleted in germ cells, facilitating determination of whether any gene of interest is expressed in the germ line or soma or both. PMID- 1289066 TI - Expression of the zinc finger gene Gli3 is affected in the morphogenetic mouse mutant extra-toes (Xt). AB - Genetic analysis and homology between the phenotypic alterations of the human Greig Cephalopolysyndactyly Syndrome (GCPS) and the mouse mutant extra-toes (Xt) have suggested a dominant mutation in the same gene of both species. Recently, the GLI3 gene, a member of the Kruppel-related zinc finger genes, has been proposed as a candidate gene for GCPS. We examined the expression of the mouse Gli3 gene in both Xt mutant animals and during normal mouse development. Northern and RNAase protection analysis of embryos revealed that Gli3 expression was reduced about 50% in heterozygous Xt/+ mice and completely absent in homozygous Xt/Xt mice. In addition, in situ analysis of wild-type mice documented Gli3 expression in the developing limb and brain, structures affected in Xt mutant mice. This pattern suggests an important function of the Gli3 gene during morphogenesis. PMID- 1289067 TI - In vitro solubility of human pulp tissue in calcium hydroxide and sodium hypochlorite. AB - The tissue solvent capacity of a 2% stabilized sodium hypochlorite solution (Milton) and a commercial calcium hydroxide solution (Calasept) was examined under in vitro conditions where autolyzed human pulp fragments weighing approximately 0.0065 g were immersed in these solutions at 37 degrees C for periods of up to 10 days. It appeared that sodium hypochlorite was able to dissolve half the volume of pulp tissue within 1 h and the remaining tissue after 2-2 1/2 h. Calcium hydroxide dissolved half the pulp volume within 2 h, whereas it took 1 week for the remaining tissue to dissolve. These findings support the use of sodium hypochlorite as an irrigation solution during canal preparation and calcium hydroxide as a canal dressing for the purpose of creating a canal free of pulp remnants before root filling. PMID- 1289068 TI - Apical root canal anatomy in the dog. AB - 240 permanent teeth from 8 different dogs aged 1, 3, 8, 10, 15 years, were used for an anatomic study. The teeth were cleaned, their root canal system was stained with dye, then the teeth were decalcified and cleared to determine the root canal anatomy. The apical root canal anatomy in dogs can be described as a "sprinkler-rose" anatomy: at the tip of the pulpal canal, the canal is divided in numerous narrow channels radiating peripherally through the dentin and the cementum and ending in numerous apical foramina on the cementum surface. This architecture constitutes a very complex apical delta. PMID- 1289065 TI - Regulation of expression of fibronectin and its receptor, alpha 5 beta 1, during development and regeneration of peripheral nerve. AB - The extracellular matrix glycoprotein, fibronectin, is a potent promoter of peripheral neurite outgrowth. Interactions of peripheral neurons with fibronectin have been shown to be primarily mediated by the beta 1 class of integrin heterodimers. In the present study, we have examined the expression and regulation of fibronectin and its integrin receptor, alpha 5 beta 1, in developing and regenerating chick peripheral nerve. We show that fibronectin and alpha 5 beta 1 are expressed at comparatively high levels in developing nerve with alpha 5 beta 1 expression on axons and non-neuronal cells. With nerve maturation, both proteins are less prominently expressed and the cellular pattern of alpha 5 beta 1 expression becomes more restricted. Following lesion of mature nerve, both fibronectin and alpha 5 beta 1 are strongly induced with prominent expression of alpha 5 beta 1 on regenerating neurites and Schwann cells. The elevation in fibronectin levels in the regenerating nerve is highest in the vicinity of the lesion, an area undergoing extensive cellular remodeling including Schwann cell migration and growth cone extension. Our results suggest that fibronectin and its receptor, alpha 5 beta 1, may mediate functionally important interactions in the development and regeneration of peripheral nerve. PMID- 1289069 TI - Rigidity of various fixation methods used as dental splints. AB - Horizontal and vertical rigidity of teeth fixed with seven types of dental splints were evaluated by two tooth mobility measuring devices. Altogether 21 dissected sheep mandibles including soft tissues were used for the experiments in which Fermit, flexible wire-composite, Kevlar, Fiber, Protemp, rigid wire composite and Triad Gel splints were applied to four incisors. The mean rigidity of the central incisors within the splint was measured by means of Muhlemann periodontometer (horizontal mobility) and Periotest (horizontal and vertical mobilities). Mobility values of teeth before splinting were used as covariants and the values with the splints were illustrated as adjusted mobility. Statistical significance between the rigidity of various splints was analyzed by an unpaired t-test. It was shown that the most rigid splints both in horizontal and vertical directions were Triad Gel, rigid wire-composite and Fermit splints. Kevlar and Fiber splint allowed more horizontal movement than other splints. Protemp and flexible wire-composite splints proved to produce adequate lateral support for the fixed teeth and allowed vertical flexibility which is experimentally known to improve periodontal healing of luxated teeth. PMID- 1289070 TI - Toxic effects of various retrograde root filling materials on gingival fibroblasts and rat sarcoma cells. AB - The aim of this in vitro study was to evaluate the effect of amalgam, glass ionomer, composite and titanium on the growth of gingival fibroblasts (GF) and rat sarcoma cells (UMR) in vitro. The cells were either obtained from gingival biopsies taken during deliberation of unerupted canines (GF) or were of commercial origin (UMR). Equal numbers of cells were placed on culture dishes and incubated for a period of two weeks with the freshly prepared test materials. The cultures were photographed through a light microscope after 7 days incubation and finally counted after 14 days. It was shown that the proliferation of gingival fibroblasts was less disturbed by titanium, being approximately 96% of the control value (cell cultures without test particles), followed by composite, amalgam and glass ionomer (61%, 49% and 35% of the control value respectively). The number of UMR cells after 14 days incubation with the various materials was 76% of the control value with titanium, 12% with composite and 5% with both amalgam and glass ionomer. Inhibition of cell growth (UMR) around the test particles was most prominent around amalgam and glass ionomer, followed by composite and titanium. These effects were noted only with freshly prepared components however, so that the toxic reaction was less pronounced or minimal in a second incubation using the same particles sterilized in between. The results demonstrated that potential retrograde root filling materials have a variable toxic effect on gingival fibroblasts and rat sarcoma cells. The fact that the influence on proliferation disappeared when the test was performed with materials already tested once may be of clinical importance when estimating the biocompatibility in vivo. PMID- 1289071 TI - Histologic evaluation of three endodontic instrument/preparation techniques. AB - 33 curved canals were prepared to quantify both the increase in canal area and predentin removal in the apical region. Compared were three different file designs/instrumentation techniques, that is "stepback" with K-flex file, "balanced force" with Flex-R file, and the Canal Master system. Following canal preparation and histological processing, cross-sections at 1 and 3 mm levels were examined using the Bioquant image analysis system. Results showed that, at the 3 mm leve, the mean increase in canal area and predentin removal showed no statistically significant difference (p > 0.05) between the techniques. At 1 mm, the step-back technique (with K-flex files) resulted in a significant increase in canal area and greater predentin removal than did the "balanced forces" (with Flex-R files) or the Canal Master system. However, although there were statistical differences, the actual differences were small; these may not translate to clinically significant differences in the 3 techniques. PMID- 1289072 TI - Traumatic gemination--triple tooth. Survey of the literature and report of a case. AB - Gemination and twinning are two rarely encountered developmental abnormalities. Although the precise etiology remains unknown, genetic predisposition is often suggested in the process. In the present study a maxillary incisor with three crowns of conical shape and three roots which were presumed to be the gemination of the tooth due to trauma, is reported. PMID- 1289073 TI - Apical closure of an immature root subsequent to apical curettage. AB - A 7-year-old female presented with a history of trauma to the mandibular central incisor resulting in pulpal necrosis and soft tissue swelling. During apexification treatment, an ultrasonic file was separated and lodged in the periapical tissues. Surgical retrieval of the broken instrument resulted in complete curettage of the periapical tissues. Apical closure occurred following intracanal calcium hydroxide therapy. The findings suggested that hard tissue barrier formation occurred despite the absence of Hertwig's epithelial root sheath and local periapical tissues. PMID- 1289074 TI - Oral defense factors in the elderly. AB - Continuously increasing proportion of elderly people in the human population creates new challenges for the dental care. Because the microbial etiology of the most common oral diseases, dental caries, endodontal and periodontal diseases, is not substantially different in different age groups, the altered host response during aging may modify the progression of these diseases. Most prevalent and severe change in the oral defense is hyposalivation or xerostomia but aging as such does not seem to reduce neither parotid nor whole salivary flow rate. However, submandibular and minor salivary glands produce less saliva at old age which may be the reason for the frequently reported symptoms of oral dryness even if the stimulated flow rate is normal. Concomitantly to the changes in the flow rate the daily output of many saliva-mediated defense factors declines but age related impairment has been described only for specific IgA response to external antigens, for salivary opsonic activity, and for T-lymphocyte function. The non immunoglobulin defense factors seem to act with full capacity over the entire life-span. Therefore, elderly people with normal salivary flow rate possess no special risk group for the development of oral diseases. PMID- 1289075 TI - Effectiveness of different endodontic files for preparing curved root canals: a scanning electron microscopic study. AB - In this study, the effect of using four endodontic files from different manufacturers on the final shape of 80 prepared curved root canals of extracted single-rooted teeth were comparatively analyzed with scanning electron microscopy. The instruments tested were Tri-files, Flex-R files, Flexofiles and conventional K-type files. All files were used with in and out linear movements with a circumferential motion starting with a size 15 file. Final preparation of the apical thirds was performed with a size 30 file. Shaping effectiveness of the tested files was qualitatively evaluated in terms of respect for conservation of the apical constriction and the presence or absence of ledging, specially in the apical third of the root canals. A well-centered and tapered preparation without apical transportation or ledging was detected when Tri-file or Flex-R files were used. Conversely, the use of Flexofile or conventional K-type files resulted in frequent alteration of the initial pattern of the root canals, showing an hour glass preparation with alteration of the apical constriction and ledge formations. PMID- 1289076 TI - The cone fit: an essential step to creating obturation excellence. PMID- 1289077 TI - Endodontic surgery: the treatment phase and wound healing. Part II. PMID- 1289078 TI - Advanced techniques and visual enhancement for endodontic surgery. PMID- 1289079 TI - Functional hepatocellular heterogeneity for the production of plasma proteins. AB - It is now well established that hepatocytes are the main liver cells responsible for the synthesis of plasma proteins produced by the liver. That these cells are not specialized in the production of the different plasma proteins is also well established. Presently the point still debated is whether a functional hepatocellular heterogeneity exists for plasma protein synthesis as for many other hepatocyte functions. Several physiological and pathological situations suggest that this heterogeneity takes place in the hepatocytes of two opposite hepatic lobular zones, the periportal and centrilobular zones. However, this zonal difference, which supposes different regulatory mechanisms, must be confirmed by techniques other than the now classical immunocytochemistry or the in situ hybridization technique recently proposed for the demonstration of mRNAs in hepatocytes. Another hepatocellular heterogeneity, the intercellular heterogeneity, which can be observed in the same lobular zone, is more difficult to analyze, but shows that from hepatocyte to hepatocyte a variation exists in the synthesis of a given plasma protein. PMID- 1289080 TI - Liver cell heterogeneity: functions of non-parenchymal cells. AB - The normal hepatic sinusoid is formed or lined by four different cell types, each with its specific phenotypic characteristics, functions and topography. Endothelial cells constitute the closed lining or wall of the capillary. They contain small fenestrations to allow the free diffusion of substances, but not of particles like chylomicrons, between the blood and the hepatocyte surface. This filtering effect regulates the fat uptake by the liver. Sinusoidal endothelial cells also have a pronounced endocytotic capacity which makes them an important part of the reticuloendothelial system. They are also active in the secretion of bioactive factors and extracellular matrix components of the liver. Recently, a zonal heterogeneity of the endothelial lining has been reported with regard to its filtering capacity (fenestration) and binding capacity for lectins and cells. Kupffer cells are intrasinusoidally located tissue macrophages with a pronounced endocytotic capacity. They are potent mediators of the inflammatory response by the secretion of a variety of bioactive factors and play an important part in the immune defense. A zonal heterogeneity has been established with regard to the endocytotic capacity and cytotoxic function. Pit cells are now known to represent a liver-associated population of large granular lymphocytes. They have the capacity to kill tumor cells and probably also play a role in the antiviral defense of the liver. In addition, pit cells may have a growth-regulatory function of the liver. They are known to be numerically more prominent in the periportal region, as is also the case for Kupffer cells. Fat-storing or Ito cells are present in the perisinusoidal space of Disse and are thought to represent the main hepatic source of extracellular matrix components. They are also the main site of vitamin-A storage. Fat-storing cells are more numerous in the periportal region than in the central region of the hepatic acinus. The periportal cells also store higher amounts of vitamin A. Sinusoidal cells may be considered to represent a functional unit at the border line between the hepatocytes or parenchymal cells and the blood. They participate in various liver functions and liver pathologies and our knowledge about this is growing. The heterogeneity of these cell types and possible cooperations between them and the hepatocytes may add to our understanding of liver functions. PMID- 1289081 TI - Hepatocyte heterogeneity in the metabolism of carbohydrates. AB - Periportal and perivenous hepatocytes possess different amounts and activities of the rate-generating enzymes of carbohydrate and oxidative energy metabolism and thus different metabolic capacities. This is the basis of the model of metabolic zonation, according to which periportal cells catalyze predominantly the oxidative catabolism of fatty and amino acids as well as glucose release and glycogen formation via gluconeogenesis, and perivenous cells carry out preferentially glucose uptake for glycogen synthesis and glycolysis coupled to liponeogenesis. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of carbohydrate metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes in carbohydrate metabolism has been well characterized. In vivo evidence is provided by the complex metabolic situation termed the 'glucose paradox' and by zonal flux differences calculated on the basis of the distribution of enzymes and metabolites. In vitro evidence is given by the different flux rates determined with classical invasive techniques, e.g. in periportal-like and perivenous-like hepatocytes in cell culture, in periportal- and perivenous-enriched hepatocyte populations and in perfused livers during orthograde and retrograde flow, as well as with noninvasive techniques using miniature oxygen electrodes, e.g. in livers perfused in either direction. Differences of opinion in the interpretation of studies with invasive and noninvasive techniques by the authors are discussed. The declining gradient in oxygen concentrations, the decreasing glucagon/insulin ratio and the different innervation could be important factors in the zonal expression of the genes of carbohydrate-metabolizing enzymes. While it is clear that the hepatocytes sense the glucagon/insulin gradients via the respective hormone receptors, it is not known how they sense different oxygen tensions; the O2 sensor may be an oxygen binding heme protein. The zonal separation of glucose release and uptake appears to be important for the liver to operate as a 'glucostat'. Thus, zonation of carbohydrate metabolism develops gradually during the first weeks of life, in part before and in part with weaning, when (in rat and mouse) the fat- and protein-rich but carbohydrate-poor nutrition via milk is replaced by carbohydrate rich food. Similarly, zonation of carbohydrate metabolism adapts to longer lasting alterations in the need of a 'glucostat', such as starvation, diabetes, portocaval anastomoses or partial hepatectomy. PMID- 1289082 TI - Zonal liver cell heterogeneity. PMID- 1289083 TI - Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. AB - With respect to hepatocyte heterogeneity in ammonia and amino acid metabolism, two different patterns of sublobular gene expression are distinguished: 'gradient type' and 'strict- or compartment-type' zonation. An example for strict-type zonation is the reciprocal distribution of carbamoylphosphate synthase and glutamine synthase in the liver lobule. The mechanisms underlying the different sublobular gene expressions are not yet settled but may involve the development of hepatic architecture, innervation, blood-borne hormonal and metabolic factors. The periportal zone is characterized by a high capacity for uptake and catabolism of amino acids (except glutamate and aspartate) as well as for urea synthesis and gluconeogenesis. On the other hand, glutamine synthesis, ornithine transamination and the uptake of vascular glutamate, aspartate, malate and alpha-ketoglutarate are restricted to a small perivenous hepatocyte population. Accordingly, in the intact liver lobule the major pathways for ammonia detoxication, urea and glutamine synthesis, are anatomically switched behind each other and represent in functional terms the sequence of the periportal low affinity system (urea synthesis) and a previous high affinity system (glutamine synthesis) for ammonia detoxication. Perivenous glutamine synthase-containing hepatocytes ('scavenger cells') act as a high affinity scavenger for the ammonia, which escapes the more upstream urea-synthesizing compartment. Periportal glutaminase acts as a pH- and hormone-modulated ammonia-amplifying system in the mitochondria of periportal hepatocytes. The activity of this amplifying system is one crucial determinant for flux through the urea cycle in view of the high Km (ammonia) of carbamoylphosphate synthase, the rate-controlling enzyme of the urea cycle. The structural and functional organization of glutamine and ammonia-metabolizing pathways in the liver lobule provides one basis for the understanding of a hepatic role in systemic acid base homeostasis. Urea synthesis is a major pathway for irreversible removal of metabolically generated bicarbonate. The lobular organization enables the adjustment of the urea cycle flux and accordingly the rate of irreversible hepatic bicarbonate elimination to the needs of the systemic acid base situation, without the threat of hyperammonemia. PMID- 1289084 TI - Liver architecture. AB - The development of liver parenchyma starts from entodermal cells which grow out from the gut into the mesenchyma of the septum transversum. In the definitive organ this close association of epithelial cells (hepatocytes) and mesenchyma derived nonparenchymal cells is maintained. The liver, and with it each hepatocyte, acts in two directions: the vascular poles of the hepatocytes serve in an ingestive sense, while at their biliary poles secretory functions are exerted. Hepatic microvascularization comprises two afferent vessels (arterial and portal terminal branches), the sinusoids and the terminal hepatic venule. Sinusoidal cells surround the capillaries but also have highly specialized functions with regard to filtration, phagocytosis, fat storage and defense. The autonomic innervation plays an important role in the regulation of metabolic functions. Above the cellular level the proper architecture of the liver parenchyma has been the object of controversial discussions for centuries. The concept of the liver lobule, the portal unit, the liver acinus and other structures are presented and discussed. Finally, the liver parenchyma is described as an irregular interdigitating system of regions related to the terminal blood vessels. PMID- 1289085 TI - Hepatocyte heterogeneity in bile formation and hepatobiliary transport of drugs. AB - In the past two decades many studies have been devoted to the involvement of the periportal (zone-1) and perivenous (zone-3) hepatocytes in bile formation and hepatobiliary transport of endogenous and exogenous compounds. It became clear that such a heterogeneity in transport function can, in principle, be due to the different localization of the cells in the acinus with respect to the incoming blood, to intrinsic differences between the cells or to both. In this review we first discuss the techniques used to study hepatocyte heterogeneity in hepatobiliary transport function. Combinations of such techniques can be used to discriminate between cellular heterogeneity due to acinar localization as opposed to intrinsic differences. These techniques include: normal and retrograde perfusions of isolated perfused livers; autoradiographic, fluorimetric and histochemical localization of injected substrates; separation of isolated hepatocytes into fractions enriched in periportal and perivenous cells; measurements of fluorescent surface signals with microlight guides; selective zonal toxicity, and pharmacokinetic modelling and analysis. Subsequently, for each of the rate-limiting steps in the hepatobiliary transport of organic compounds, the basic mechanisms are summarized and the available knowledge on the involvement of the cells from the various zones in these transport steps is discussed. The available literature data indicate that heterogeneity in transport function is often due to the localization of the cells in the acinus: the periportal cells are the first to come into contact with the portal blood and are thus exposed to the highest substrate concentration. Consequently they obtain the most prominent task in further disposition of the particular compound. It follows that the extent of involvement of the perivenous cells in drug disposition is implicitly determined by the activity of the periportal cells. Because of the potential saturation of elimination processes in the periportal cells, the involvement of perivenous cells may vary with the input concentration. In addition, real intrinsic differences have been established in the hepatobiliary transport of some substrates. These are probably based on differences in the cellular content of carrier- and receptor-binding and/or metabolizing proteins. In some cases these intrinsic differences may be secondary to existing sinusoidal gradients of endogenous compounds, such as O2, amino acids, bile acids or monosaccharides. Yet, data on the heterogeneity of hepatocytes in the various transport steps are far from complete or are even totally lacking, especially for human liver. A multi-experimental approach and advanced technology will be needed in the future to gain more insight into the acinar organization of bile formation and hepatobiliary transport of drugs in the human. PMID- 1289086 TI - Survival of hypertensive subjects identified on screening: results for sustained and unsustained diastolic hypertension. AB - Casual readings of blood pressure predict mortality and may reflect either the risk of sustained hypertension, additional components of 'white coat' hypertension or variable blood pressure. This study investigated mortality in 442 men and 360 women with a diastolic pressure (Phase IV) of 90 mmHg and over, unsustained on two subsequent monthly visits, followed for an average of 11 years and compared with a matched control cohort with an initial diastolic pressure (DBP) of less than 90 mmHg. Subjects were identified between 1975 and 1979 by screening 28,257 subjects aged 18-65 years on the lists of general practitioners in seven practices in the United Kingdom. Additionally, 912 men and 844 women with sustained hypertension (DBP > 90 mmHg on at least two out of three occasions) were identified and matched with normotensive controls. In men with sustained hypertension the relative risk (RR) for death from circulatory disease was 1.76, P < 0.01, 95% confidence interval 1.21, 2.58 and in women 1.85, P < 0.05, 95% confidence interval 1.06, 3.24 respectively, while in men with unsustained hypertension the RR = 1.52, P = 0.2, 95% confidence interval 0.81, 2.84. Few circulatory deaths occurred in women with transient hypertension or their controls (five and seven respectively). Despite the screening programme and further treatment, newly discovered subjects with sustained hypertension, both men and women, remain at high risk of cardiovascular mortality. The 95% confidence interval for men with transient hypertension does not exclude a similar adverse effect. PMID- 1289087 TI - Height: a risk marker for ischaemic heart disease: prospective results from the Caerphilly and Speedwell Heart Disease Studies. AB - The predictive power of height for future ischaemic heart disease (IHD) was examined in 4860 men from two communities in South Wales and the West of England. At follow-up, men in the shortest fifth of the height distribution had experienced twice as many incident IHD events (fatal and non-fatal myocardial infarction) as was the case for men from the tallest fifth. Adjustment for age, social class and smoking habit failed to alter these relationships significantly. In the data from South Wales, determinants of height were examined; birth rank and number of siblings showed a trend with height. This trend was found only in men whose fathers were manual workers and may be related to inadequate nutrition in the higher birth ranks and larger families. These results support the suggestion that early childhood factors may be relevant to IHD in middle age and possible mechanisms are discussed. PMID- 1289088 TI - Reproducibility of electrocardiographic criteria for left ventricular hypertrophy in hypertensive patients in general practice. AB - Before changes in ECG voltage criteria can be accepted as evidence for changes in LVH, the variability of ECG measurements must be known. Here we report on the results of a study, on the variability of electrocardiographic single lead voltage parameters and (voltage) criteria for left ventricular hypertrophy in hypertensive patients in general practice. Two electrocardiograms were recorded, from 64 patients at an interval of 2 min, to measure the minute-to-minute variability. From 77 patients, two electrocardiograms were recorded at an interval of one week to measure the day-to-day variability. The coefficient of variation of voltage parameters for single leads ranged in the day-to-day group from 9.2% in R/I to 42% in T/V1, and the coefficient of variation for voltage combinations in this group ranged from 10.0% for the Sokolow-Lyon criteria to 13.7% for Gubner-Ungerleider criteria. The reclassification percentages in the day-to-day group ranged from 0% for Gubner-Ungerleider to 17% for Minnesota code criteria. A factor analysis showed that studies which use the Romhilt-Estes score, the Sokolow-Lyon or the Minnesota criteria to detect ECG-LVH are not comparable with studies which use the Cornell or Gubner-Ungerleider criteria. PMID- 1289089 TI - Prognosis after recovery from myocardial infarction: the relative importance of cardiac dilatation and coronary stenoses. AB - In order to further define clinical and angiocardiographic predictors of long term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction. PMID- 1289090 TI - ST segment analysis for assessment of coronary artery patency: comparison of surface ECG and Holter recordings. AB - In a prospective trial in 124 patients with acute myocardial infarction, Holter and surface ECG recordings were obtained simultaneously and compared for their ability to assess thrombolysis-induced ST segment changes. Accuracy in predicting patency of the infarct-related artery was evaluated in both methods. Success or failure of thrombolysis was determined angiographically 90 min after the start of therapy. For both methods, sensitivity, specificity, and positive predictive value for correct prediction of the perfusion status ranged between 64% and 92%. However, the negative predictive value was considerably lower (40-53%). There were no significant differences in any parameter evaluated for either method. Thus, two surface ECG recordings before and 2 h after the start of therapy yield the same predictive value as continuous Holter monitoring with respect to thrombolysis-induced coronary artery reperfusion. However, for triage of patients to early coronary interventions, more sophisticated methods are needed for non invasive prediction of coronary artery patency due to the low negative predictive value of ST segment analysis. PMID- 1289091 TI - Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate? AB - The objective of this blinded, randomized, prospective study was to assess whether supplementation of normal diet with omega-3 polyunsaturated fatty acids can reduce angiographically defined restenosis following coronary angioplasty. The study included all patients undergoing coronary angioplasty in this institution between January 1988 and January 1989. One hundred and twenty patients enrolled, 60 in each treatment group. All were randomized to either supplementation of normal diet with 3 g of omega-3 polyunsaturated fatty acids per day started 1-2 days prior to angioplasty and continued for 6 months (treatment group), or to receive standard therapy only (control group). Quantitative angiographically defined restenosis was assessed at 6 months post angioplasty. Restenosis occurred in 27.8% (95% CI 18.0-37.7%) of lesions in the treatment group and in 28.3% (CI 16.9-39.7%) of lesions in the control group, but the difference was not statistically significant. The study showed that diet supplemented with 3 g of omega-3 polyunsaturated fatty acids started 1-2 days preceding angioplasty does not reduce angiographically defined restenosis rate. PMID- 1289092 TI - Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease. AB - The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289093 TI - Isolated single coronary artery: a review of 50,000 consecutive coronary angiographies. AB - Single coronary artery is a rare congenital anomaly of the coronary arteries where only one coronary artery arises from the aortic trunk by a single coronary ostium, supplying the entire heart. A database consisting of the angiographic reports of 50,000 consecutive coronary angiographies performed in adult patients in the University Hospital of Leuven between March 1973 and August 1991 was searched for the diagnosis of single coronary artery. All films concerned were reviewed and classified according to their anatomical type. Thirty-three cases of single coronary artery were retrieved, yielding an incidence of 0.066%. Patient characteristics and clinical data are described, with a discussion on the pathological importance of this finding. PMID- 1289094 TI - Lack of platelet-activating factor release during reversible myocardial ischaemia. AB - Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production. PMID- 1289096 TI - Therapy for acute vascular complications in percutaneous transluminal coronary angioplasty with the autoperfusion balloon catheter. AB - Prolonged dilatation with an autoperfusion balloon catheter (APBC) (High-Flow-CPC Mainz (Schneider) in 23 cases and Stack Perfusion (ACS) in 50 cases) was carried out in 73 patients (60 men, 13 women, mean age 59.3 +/- 8.8 years) with acute vascular complications occurring during PTCA (25 occlusive dissections (34%), five thrombotic occlusions (7%), 42 non-occlusive dissections (58%) and one non occlusive thrombus with reduction of flow (1%)) in order to avoid stent implantation or emergency bypass surgery. On average 1.5 +/- 0.8 inflations were carried out per patient with a mean maximum inflation time of 14.1 +/- 8.4 min and a mean total inflation time of 16.8 +/- 12.3 min. In 61 patients (83.5%), the vascular complication could be controlled successfully with APBC, but in 12 APBC was not successful. Eight patients (11%) had emergency surgery. A stent was implanted in three patients (4.1%), and one suffered an acute myocardial infarction. Out of the 61 patients with positive result after prolonged dilatation, the hospital phase was uncomplicated in 53 (86.9%), five (8.2%) suffered an infarct with a maximum rise in CK of 350 U.l-1, two with multivessel disease had elective operations and one was dilated a second time because of a subacute reocclusion. Our experience indicates that when an acute vascular complication occurs, prolonged dilatation with an APBC is good interventional therapy avoiding stent implantation or emergency bypass surgery. However, new techniques cannot always replace surgery so an emergency bypass operation may still be necessary. PMID- 1289095 TI - Anticardiolipin antibodies and coronary heart disease. AB - Arterial or venous thrombotic events have been described as complications in patients with positive anticardiolipin antibodies (aCL), affecting various organs including the heart. In order to see whether aCL could be, among others, a predisposing factor for coronary artery occlusions and whether it could serve as a prognostic marker for coronary heart disease, 232 patients enrolled in the European Concerted Action on Thrombosis Angina Pectoris Study were studied. aCL and various other haemostatic parameters were determined at time of admittance in order to see whether a relationship existed between haemostasis at baseline and extent or prognosis of the cardiovascular disease. A follow-up at 12 and 24 months after angiography included information about relapsing coronary or other thrombotic events, treatment and outcome of the disease. aCL were not found to be a marker of either progressive cardiovascular disease or recurrent thrombotic events. No correlation was found, either in aCL positive or in aCL negative patients, between high levels of haemostasis activation markers, such as beta thromboglobulin, platelet factor 4 or fibrinopeptide A and recurrent cardiovascular disease. PMID- 1289097 TI - Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis. AB - Normal gestation is associated with a hyperdynamic adaptive state. The circulatory changes represent an additional burden on the cardiovascular system of women with rheumatic mitral stenosis (MS). Life-threatening complications can occur in pregnant women with severe MS. We successfully performed percutaneous balloon mitral valvotomy (PMV) in eight pregnant patients (mean age 28 +/- 6.9 years, range 21-38 years). Pregnancy mean age was 24.6 +/- 6.5 weeks. Five patients were in NYHA functional class III and three patients were in class IV. Emergency PMV seemed to be life saving to both mother and foetus in one case. All patients but one had pliable valves. PMV was achieved using the double balloon transseptal technique. To protect the foetus from radiation, the patient's pelvic abdominal area was shielded and left ventriculography was not performed. The total mean time of PMV was 72 +/- 19 min and that of fluoroscopy was 16.6 +/- 7.8 min. Gorlin's mitral valve area increased from 0.83 +/- 0.15 to 2.4 +/- 0.34 cm2 and the cardiac index from 3.1 +/- 0.77 to 4.2 +/- 0.79 l.min-1.m-2. Left atrium pressure decreased from 29 +/- 10 to 14 +/- 5 mmHg and mitral valve gradient from 21 +/- 7 to 6 +/- 3 mmHg. There were no complications or residual MS. At a mean follow-up of 13.2 +/- 9.4 months, all patients were in NYHA class I and had a normal course of pregnancy. The eight women delivered healthy full-term babies. At 1-25 months post-partum follow-up, the eight infants had shown normal growth and development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289098 TI - On-line quantification of ventricular function during dobutamine stress echocardiography. AB - To develop an approach for on-line quantification of left ventricular size and function during pharmacological stress testing we employed echocardiographic automatic edge detection via integrated backscatter imaging during dobutamine infusion in 27 patients. Ventricular cavity areas, fractional area change and rate of cavity area change were obtained on-line with instantaneous graphic display of the data. When compared to baseline image data, patients with a normal response exhibited modest (15%) reduction in end-diastolic cavity areas at peak dobutamine level, but marked (33%) reduction in systolic areas yielding a 52% increase in fractional area change (n = 13; P < 0.001). The second group of patients (n = 14) had an abnormal response characterized by limited changes in measured parameters of ventricular function and reduced fractional area change (P < 0.05). On-line quantification during pharmacological stress echocardiography is a promising addition to the test for surveillance and objective instantaneous evaluation of global cardiac responses. PMID- 1289099 TI - Assessment of left ventricular volumes by magnetic resonance in comparison with radionuclide angiography, contrast angiography and echocardiography. AB - The present study shows that for assessment of LVEF, MRI and the standard methods seem to provide information of similar value. For absolute volume measurements, MRI and RNA are superior to single plane angiography and 2 DE using the modified Simpson-rule. The time consuming transversal MRI method does not seem to be superior to the oblique multislice method, when apical aneurysms can be ruled out. MRI thus seems to be an accurate method for determination of LV stroke volume as well as for determination of LVEF and hence for diastolic and systolic volumes. MRI, however, depends of a good image quality, which is crucial especially in dilated ventricles containing stagnant or slowly moving blood. PMID- 1289100 TI - The acute effects of intravenous nisoldipine on left ventricular function within 24 h after acute myocardial infarction. AB - Nisoldipine is a calcium antagonist with potent coronary vasodilating effects in patients with chronic stable angina pectoris. We studied the acute effects of nisoldipine in six patients within 24 h (mean 14 +/- 4 h) after the onset of myocardial infarction. Nisoldipine was administered as a 4.5 micrograms kg-1 intravenous bolus over 3 min followed by intravenous infusion of 0.2 microgram kg 1 min-1 during 60 min. Radionuclide angiography, cardiac output and intra arterial blood pressure measurements were performed before and during nisoldipine. Left ventricular ejection fraction increased from 48.3 +/- 10.3% to 55.3 +/- 11.8% (P = 0.034) during nisoldipine infusion. Regional wall motion score changed during nisoldipine infusion from 3.3 +/- 2.5 to 1.8 +/- 2.6 (P = 0.027). Cardiac output increased from 5.5 +/- 1.0 to 7.3 +/- 1.3 l min-1 (P = 0.0001). Heart rate increased from 78 +/- 12 to 88 +/- 11 beats.min-1 (P = 0.004). Mean arterial blood pressure decreased from 91.7 +/- 20.2 to 78.7 +/- 13.1 mmHg (P = 0.038). The rate-pressure product did not change significantly during nisoldipine infusion. It is concluded that nisoldipine improves global and regional left ventricular function in patients with acute myocardial infarction within the first 24 h. Our findings suggest that this effect is achieved without increasing myocardial oxygen demand. PMID- 1289101 TI - Six-month survival in 20,891 patients with acute myocardial infarction randomized between alteplase and streptokinase with or without heparin. GISSI-2 and International Study Group. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto. AB - This 6-month follow-up of the patients recruited into the GISSI-2 Study and the International Study substantially confirmed the in-hospital results. The aim was to compare the effectiveness and safety of alteplase (tPA) and streptokinase (SK), and of heparin and no heparin, in patients with acute myocardial infarction in an open multicentre randomized trial with a 2 x 2 factorial study design. Six months' mortality rates were similar for patients randomized to tPA or SK (12.3% vs 11.7%, RR = 1.06, 95% CI 0.97-1.15) and for patients randomized to heparin or no heparin (11.9% vs 12.1%, RR = 0.98, 95% CI 0.90-1.07). Mortality rates were also similar between randomized treatments in the pre-defined subgroups: sex, age above and below 70 years, with and without previous myocardial infarction, Killip class at entry and randomization within 3 h or between 3 and 6 h from onset of symptoms. Reinfarction and cerebrovascular accidents were similar in all treatment groups. Adjusted analysis (Cox model) indicated that age and higher Killip class were the most important predictors of a poor prognosis. Previous myocardial infarction, female sex and longer delay from onset of symptoms were also indicators. Patients treated with SK plus heparin have a statistically significant better survival than the others, although the statistical significance of the remaining absolute difference disappears once the substantial proportion of patients dying in the first 12 h is excluded, when, by design, no heparin was given. PMID- 1289102 TI - The mechanisms underlying the increased ventilatory response to exercise in chronic stable heart failure. AB - Chronic heart failure is a common clinical condition with a high mortality and morbidity. Patients with the condition suffer from shortness of breath and fatigue on exercise. This article reviews the recent advances made in the understanding of the pathophysiology of chronic heart failure and explores further possible research options. PMID- 1289103 TI - Deletion of mitochondrial DNA in the endomyocardial biopsy sample from a patient with Kearns-Sayre syndrome. AB - A 15-year-old boy with Kearns-Sayre syndrome is reported. The deletion of mitochondrial DNA in the endomyocardial biopsy sample from the patient was confirmed by the polymerase chain reaction method, and was identified to that in the skeletal muscle. PMID- 1289104 TI - Concurrent post-streptococcal carditis and glomerulonephritis: serial echocardiographic diagnosis and follow-up. AB - The two non-suppurative post-streptococcal events, acute rheumatic fever and acute glomerulonephritis, rarely occur simultaneously. We describe such a patient, a 16-year-old male who was admitted with fever, agitation and confusion. Blood work-up showed high antistreptolysin O titre, raised serum creatinine and low complement levels. Urinalysis showed RBC casts. Echocardiographic examination demonstrated markedly impaired left ventricular systolic and diastolic function and three large thrombi in the apex. Serial echocardiographic examinations revealed improvement of cardiac function and the resolution of the thrombi and both cardiac and renal function returned to normal after 3 weeks of treatment. PMID- 1289105 TI - Right atrial thrombus migration during echocardiography: a case for urgent intervention. AB - A 65-year-old woman presented with increasing shortness of breath, chest pain and ST-T wave abnormalities on the electrocardiogram suggestive of unstable angina. Cross-sectional echocardiography performed to assess wall-motion abnormality and left ventricular function revealed a pedunculated right atrial thrombus prolapsing into the right ventricle which suddenly dislodged and migrated into the pulmonary circulation during the examination. A diagnosis of recurrent pulmonary thromboembolism was made, necessitating urgent pulmonary angiography with infusion of streptokinase. The patient made an uneventful recovery. PMID- 1289106 TI - Right atrial invasive thymoma with protrusion through the tricuspid valve. AB - A patient with superior caval vein compression due to malignant thymoma with infrequent intracavitary cardiac growth is presented. Diagnostic accuracy of cardiac involvement was higher using transesophageal echocardiography compared to transthoracic echocardiography. The majority of the rare intracavitary cardiac thymomas seem to be confined to the right side of the heart. PMID- 1289107 TI - The heart as a bass organ. AB - Many florid physical signs of aortic regurgitation have been described. We describe a florid investigational finding of virtually monotonous intracardiac reverberation originating at the aortic valve leaflets. PMID- 1289108 TI - Not just a country doctor: Edward Jenner, scientist. PMID- 1289109 TI - The benefits and risks of mammographic screening for breast cancer. PMID- 1289110 TI - Meta-analysis: state-of-the-science. PMID- 1289111 TI - Eosinophilia-myalgia syndrome: coming to grips with a new illness. AB - In late October 1989, over 1,500 cases of an unusual illness involving severe myalgia and striking peripheral eosinophilia were reported in the United States and several other countries. Other clinical manifestations included pulmonary involvement (interstitial infiltrates and pleural effusions), skin rash and edema, axonal polyneuropathy, perimyositis, and possible adverse neurocognitive effects. Because of the primary manifestations of the illness, it was named "eosinophilia-myalgia syndrome" (EMS) by the Centers for Disease Control. Epidemiologic studies clearly linked illness to the ingestion of tryptophan produced by a single manufacturer in Japan, and the time course of the epidemic was most consistent with its being caused by a product contaminant. Epidemiologic analysis of plant operating conditions and data obtained from chemical analyses of case- and control-associated lots implicated 1,1'-ethylidene-bis(tryptophan) (EBT) as a candidate for the compound that causes EMS. However, the etiologic significance of EBT is still uncertain. Factors found to increase a person's risk for EMS included higher tryptophan dose and older age. Although cases occurred predominantly in women and patients had frequently been taking other medications concurrently with tryptophan, sex and use of several categories of other medications were not shown to influence the risk of illness. Few patients recovered rapidly and fully from the disease. Many were treated with glucocorticoid medications, and although they may have benefited from therapy in the short term, the development of chronic sequelae of EMS appears not to have been prevented. Public health practitioners currently depend on the reports of alert clinicians to detect this type of outbreak. In this case, state and federal government epidemiologists, once they were notified, were able to develop substantial basic information about the epidemic in a relatively short time. Control measures were introduced rapidly, effectively stopping the epidemic. PMID- 1289112 TI - Measurement of past diet: review of previous and proposed methods. PMID- 1289113 TI - Persistent diarrhea in children: epidemiology, risk factors, pathophysiology, nutritional impact, and management. PMID- 1289115 TI - Update--the United States measles epidemic, 1989-1990. PMID- 1289114 TI - Epidemiology of pertussis and reactions to pertussis vaccine. AB - It remains clear that pertussis is a dangerous infectious disease that is well controlled in industrialized countries by widespread immunization. In the developing world, it remains a source of high morbidity and mortality because of previously inadequate immunization programs. However, because of the intense efforts of the World Health Organization's Expanded Programme on Immunization, the effects of pertussis have already been ameliorated and show promise of being within a decade of approximating the situation in the developed world. Pertussis can be controlled only by immunization; other measures such as antimicrobial therapy offer negligible benefit. A problem that has been addressed in recent years is the excessive reactivity of whole-cell pertussis vaccine, which undoubtedly includes components of the organism that are irrelevant to the induction of immunity and are excessively reactive. Although epidemiologic studies appear to have largely, if not completely, absolved pertussis vaccine of responsibility for inducing death or permanent neurologic disability, a less reactive vaccine is highly desirable, not only to promote acceptance of a full course of immunization for the world's children but also for simple humanitarian reasons. Additionally, it has become evident that, because of waning immunity, pertussis increasingly occurs in adults. A less reactive vaccine would offer opportunity for reinforcement of immunity beyond childhood. The development of better, though as yet incomplete, understanding of the biology of Bordetella pertussis and its relation to humanity offers the opportunity for the production of less reactive vaccines free of irrelevant components. Acellular pertussis vaccines have been used exclusively in Japan for more than 10 years, and one such preparation, combined with diphtheria and tetanus toxoids, was licensed in the United States in late 1991 for use as the fourth and fifth doses of DTP, given at 15 months and prior to school entry. Field trials of this and other acellular DTP preparations are currently under way to determine their clinical efficacy in infants. It is probable that, within a very few years, whole-cell pertussis vaccine will be replaced by these newer preparations and that, in addition, the acellular product will be combined with other antigens, such as Haemophilus influenzae type b vaccine. PMID- 1289116 TI - Physical activity, physical fitness, and sudden cardiac death. PMID- 1289117 TI - Epidemiology of Alzheimer's disease. PMID- 1289118 TI - Reproductive effects of caffeine: a review and theoretical analysis. PMID- 1289119 TI - Connectedness versus separateness: applicability of family therapy to Japanese families. AB - This article, a product of the two authors' multicultural experiences, contrasts British and Japanese families in order to examine the applicability of the Western model of family therapy to Japanese families and therapists. Areas where the Western model is incompatible are identified, and modifications to fit the Japanese indigenous model are suggested. The most significant difference in value systems between the two cultures is the Japanese preference for connectedness. The Japanese person is seen as a part of the embedded interconnectedness of relationships, whereas British norms prioritize separateness and clear boundaries in relationships, individuality, and autonomy. This value orientation is manifested in the Japanese language, hierarchical nature of the family structure, the family life cycle, and the implicit communication style. Systemic thinking, which deals with the pattern of relationships, is valid for all families regardless of cultural differences. But therapists should note that the preferred direction of change for Japanese families in therapy, is toward a process of integration--how a person can be effectively integrated into the given system- rather than a process of differentiation. An authoritative therapist style, the use of individual sessions, silence, and other nonverbal techniques are relevant to bringing about the desired change toward better integration of the individual with his or her networks. PMID- 1289120 TI - Families with adolescents: escaping problem lifestyles. AB - Using the concepts of "restraints" and reciprocal patterns, a specific approach for understanding and working with families of adolescents is offered. The organizing idea is the "restraint" that revolves around a difficulty both parents and youngsters have in making a distinction between what parents want for their youngsters and what the young person might want. This difficulty may come from the parents' ideas and beliefs about parenting and from their own growing-up experience, from the adolescent's "not completely storied" lives, and/or from societal discourse about adolescence. Restraint of ideas can be constructed as reciprocal patterns and located in dominant narratives that families may have about themselves. A restorying process allows families to separate from the problem pattern and focus on the youngsters' willingness to have ideas for themselves. PMID- 1289121 TI - Working with projective identification in couples. AB - Couples therapists spend considerable time focused on the recurring patterns of anger and misunderstanding that occur in their sessions. These patterns usually represent projective identification sequences in which one partner disavows disturbing thoughts and feelings, and, instead, unconsciously induces similar thoughts and feelings in the other partner by behaving in such a way as to stimulate them. Conflict and misunderstanding surround the partners' shared efforts to avoid identifying with the undesirable thoughts and feelings. The underlying problem is each individual's inability to contain the disturbing material and provide holding for the other partner. This article offers a technique for interrupting the process and helping each partner to identify with and contain the disturbing material. PMID- 1289122 TI - The importance of similarity in the marital relationship. AB - Concepts such as "agreement," "consensus," "understanding," and "shared meaning" are very familiar to clinicians. It is argued in this article that similarity in perceptions between spouses is a crucial dimension of the family system underlying these concepts. Findings are presented that support the idea that families vary along a dimension of similarity of perceptions, with more functional families characterized by high similarity between spouses' perceptions of their marriage and their family. In addition, the structure of this similarity was stable over 2 years and little change occurred in the mean level of similarity. Of three sets of predictor variables--psychological stress, marital cohesion, and structural variables--marital cohesion was the most powerful predictor of marital similarity. The importance of similarity of perceptions between family members in clinical work is discussed. PMID- 1289123 TI - Lives in a balance: perceived family functioning and the psychosocial adjustment of adolescent cancer survivors. AB - Childhood cancer patients have a greater likelihood of long-term survival than ever before. This study examined both the perceived family functioning of adolescents who had successfully completed treatment for pediatric cancer and the relationship between family functioning and post-treatment adjustment. Eighty eight adolescent survivors of hematologic malignancies were assessed regarding their family functioning, mental health, self-esteem, global competence, and problem behaviors. Contrary to expectations about the influence of cancer on these families, adolescent cancer survivors reported lower levels of family cohesion than the normative sample of healthy adolescents and their families. While current age, gender, age at diagnosis, and time since treatment completion were generally not associated with adolescents' adjustment, perceived family cohesion and adaptability were strongly related to post-treatment psychological adjustment. PMID- 1289124 TI - The California Family Health Project: IV. Family structure/organization and adult health. AB - This research explores the relationships between each of four "domains" of family life and the health of husbands and wives in a community-based sample of 225 families. In this article we report the association between Family Structure/Organization and adult Health. This family domain refers to the architecture of the family or the structural frame of roles and rules within which the family operates. Interrelationships among 13 self-reported, family Structure/Organization scales are described, using principle components analysis (PCA) and multidimensional scaling analysis (MDS). Derived, joint-spouse or couple Structure/Organization variables also were created using inter-battery factor analysis. The PCA yielded a poor solution, whereas the MDS yielded a good two-dimensional solution, which roughly displayed the scales in a circular pattern for both husbands and wives. The analyses indicated that no single dimension or set of separate subdimensions adequately described the Structure/Organization variables. All 13 scales than were associated with a battery of 14 adult health scales for husbands and wives separately, using canonical correlation. Different aspects of family Structure/Organization were correlated with health for husbands and wives: Organized Cohesiveness, Sex Role Traditionalism, Role Flexibility and Shared Roles for husbands; and Organized Cohesiveness and Differentiated Sharing for wives. Different patterns of health scores also emerged by gender, with behavioral indicators, such as Smoking and Drinking, more salient for husbands, and mood indicators, such as Anxiety and Depression, more salient for wives. PMID- 1289125 TI - The California Family Health Project: V. Family problem solving and adult health. AB - This article explores the relationship between family Problem Solving and the Health of adults in a community-based sample of 225 families. Family Problem Solving refers to the ways in which the family conducts itself to resolve a shared problem. Sixteen observer ratings of family Problem-Solving behavior during a 30-minute task were developed, based on the Simulated Family Activity Measure (SIM-FAM), and good interrater agreement was achieved. Principal Components Analysis (PCA) yielded a set of three well-constructed, interpretable dimensions: Problem-Solving Effectiveness, Problem-Solving Style, and Sociomotor Activity. Multidimensional scaling analyses (MDS) suggested that family problem solving behavior involved an organized, means-end sequence of family behaviors in which aspects of style served problem-solving effectiveness. All 16 Problem Solving variables were analyzed with a set of 14 health variables, for husbands and wives separately, using canonical correlation. No subset of Problem-Solving variables was significantly associated with a subset of Health variables for either husbands or wives, although there was a significant association between the two sets of variables when taken as a whole. Given previous research on family Problem Solving, we conclude that the absence of significant associations between particular aspects of family Problem Solving and Health may be due to our use of a community-based rather than a stressed or clinical sample. Associations between Family Problem Solving and Health might best be viewed in the context of other family variables. PMID- 1289126 TI - The therapeutic system as viewed by depressive inpatients and outcome: an expanded study. AB - In an expansion of a previous study, we examined in which way depressive inpatients' views of psychiatrists' and significant others' attitudes toward the severity of their illness were related to outcome. Fifty-six patients were asked a two-part question--"Who regards your illness as being more severe: (a) you or your significant others; (b) you or your psychiatrist?" Two subsamples of patients were identified: those who viewed the psychiatrists' and significant others' attitudes as similar and those who viewed them as dissimilar. Both groups showed substantial and significant improvement during hospital treatment; but the group that viewed the attitudes held by psychiatrists and significant others as dissimilar had significantly fewer depressive symptoms by the end of a 3-month followup period. The findings were consistent with those of the original study, and with the hypothesis as derived from the Mental Research Institute brief therapy principles. PMID- 1289127 TI - The vitreous. PMID- 1289128 TI - Anatomy and pathology of the vitreo-retinal interface. PMID- 1289129 TI - The chemical morphology of the vitreous. AB - The water of the vitreous is stabilised by an ordered meshwork of very fine collagen fibrils that are tied together in loosely parallel bundles or sprays by bridges of sulphated glycosaminoglycan. Some fibril bundles run at right angles to other bundles. In these respects vitreous resembles a very dilute corneal stroma. The glycosaminoglycans of the vitreous (hyaluronan and chondroitin sulphate) aggregate with themselves and with each other in solution. The protein cores of the proteoglycans are attached to collagen fibrils. Thus, a three component cross-linked structure is formed: collagen fibril-->proteoglycan protein core-->glycosaminoglycan chain-->glycosaminoglycan chain-->protein core- >collagen fibril. Hyaluronan can aggregate directly with chondroitin-6-sulphate, or with aggregated glycan cross-links, thus entering into an infinite meshwork. PMID- 1289130 TI - Mathematical modelling of the elastic properties of retina: a determination of Young's modulus. AB - The retina can be regarded as an elastic membrane or sheet which stretches and deforms when a force is applied to it. Isolated bovine retina was taken and a graded traction force applied to determine retinal profile as a function of force. The resulting profile can be modelled mathematically and the model then used to determine a value for the elastic constant. The value of the elastic constant obtained by this method is approximately 2 N/m. This value of the elastic constant, combined with the observed retinal thickness, yields a value of Young's modulus for retina of approximately 2 x 10(4) Pa, which is about 2 orders of magnitude weaker than typical rubber. This value can then be used in modelling retinal behaviour in vivo when forces are applied to detached retina. PMID- 1289131 TI - Modulators and milieu in preretinal neovascularisation. PMID- 1289132 TI - Thrombospondin as a component of the extracellular matrix of epiretinal membranes: comparisons with cellular fibronectin. AB - We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes. PMID- 1289133 TI - Removal of scleral explant elements: a 10-year retrospective study. AB - There are several studies in the American literature on the incidence and causes of retinal redetachment following removal of explants. This is, to our knowledge, the first such study from Britain and differs in its findings from the American experience. The reason for removal of explants, the time of removal after initial detachment surgery and the consequences of removal were reviewed for the 10-year period from 1980 to 1990. During this period 1898 retinal detachment operations were performed at this centre, with an explant removal rate of 3.2% (61 eyes). Extrusion of the element was the cause in 74%. Of these 8% subsequently suffered a redetachment. In two eyes no retinal break was identified at initial surgery. Both of these suffered a redetachment following removal of the explant. Contrary to previous reports, redetachment was not related to short periods of explant or to infection of the explant. This study suggests that explant removal is a safe procedure. However, there is a significant risk of redetachment after explant removal if no breaks are identified at the time of initial surgery. PMID- 1289134 TI - Four-quadrant local anaesthesia technique for vitreoretinal surgery. AB - We report our experience of a recently described local anaesthetic technique which seeks to avoid risk of perforation of the globe, damage to the optic nerve, or injection into the subarachnoid space, whilst providing prolonged and reliable anaesthesia. A prospective series of 19 patients who underwent vitreoretinal surgery using this technique were compared with 19 patients who had retrobulbar anaesthesia for cataract extraction. The vitreoretinal group had excellent akinesia and very good anaesthesia, allowing prolonged retinal reattachment surgery lasting up to 3 hours. Patient evaluation of discomfort or pain experienced in the two groups was assessed using a visual analogue pain score chart. The pain scores for the two groups were not significantly different (p = 0.03) and 16 of 19 patients in each group (84%) experienced only slight pain or less. Satisfaction with local anaesthesia, in both groups, was also assessed by asking patients which method of anaesthesia they would prefer if future surgery were to be performed. In the vitreoretinal group, 18 of 19 patients expressed a preference for local anaesthesia and in the cataract group 17 ot 19 also favoured local anaesthesia. The vitreoretinal patients' median pain score was 0 compared with 1 for the cataract patients. This study demonstrates that local anaesthesia provides pain relief for vitreoretinal surgery which is comparable to the experience of patients undergoing cataract surgery by retrobulbar anaesthesia. The technique described can provide successful local anaesthesia for vitreoretinal procedures. The success of this technique for pain relief and akinesia calls for a reappraisal of the number of patients suitable for vitreoretinal surgery under local anaesthesia. PMID- 1289135 TI - Tumour fluorescence and tumour-associated fluorescence of choroidal melanomas. AB - 'Tumour fluorescence' occurs within the tumour itself and is inversely related to the degree of pigmentation of the tumour, whereas 'tumour-associated fluorescence' occurs within the retinal pigment epithelium and retina as a result of degenerative changes in these structures; these secondary changes can collectively be termed 'tumour-associated retinal pigment epitheliopathy'. Tumour fluorescence should be differentiated from tumour-associated fluorescence so as not to confuse naevus with melanoma and to facilitate the interpretation of angiographic changes after radiotherapy or photocoagulation of choroidal melanomas. PMID- 1289136 TI - Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid. AB - Sensitisation to retinal S-antigen has been implicated in the pathogenesis of several clinical forms of posterior uveitis. S-antigen-like molecules have recently been demonstrated in the brain and choroid plexus of experimental animals. We used a panel of four monoclonal antibodies (MAbs), MAbF4-C1, MAbC10 C10, MAbA2-G5 and MAbA9-C6, which define specific epitopes in the amino, mid and carboxyl terminal portions of S-antigen in order to identify an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid (CSF). Three MAbs, MAbF4 C1, MAbC10-C10 and MAbA9-C6, localised an S-antigen-like molecule to the cytoplasm of the epithelial cells of the human choroid plexus. Polymerase chain reaction of cDNA from choroid plexus verified the presence of S-antigen homologues in the choroid plexus. The presence of an S-antigen-like molecule in the CSF was demonstrated by western blots in seven CSF samples from patients with a variety of neuropathological disorders. It is proposed that immunological cross reactivity and biochemical similarity between retinal S-antigen and an S-antigen like molecule in human choroid plexus and CSF could form a basis for neurological manifestations observed in certain clinical forms of uveitides. PMID- 1289137 TI - Results of early surgery for infantile esotropia in normal and neurologically impaired infants. AB - A prospective study was performed over a 4-year period of 56 infants presenting with infantile esotropia to assess development of binocularity after surgical alignment before 2 years of age. In 50% of cases infantile esotropia was associated with neurological problems or prematurity. Forty-three cases have undergone surgery (mean age 15.7 months +/- 3.46); 86% were aligned (+/- 10 dioptres) at 2 years. Eighty-seven per cent of normal children and 74% of children with neurological problems or prematurity were aligned at last follow-up (mean 27.2 months since surgery). Tests of fusion and stereopsis have to date been possible upon 21 'successfully' aligned infants and although most have evidence of peripheral sensory fusion none showed stereopsis to more than one test. Although early surgery achieves a good cosmetic result in normal children and those with neurological problems, our findings question its ability to promote the development of even gross stereopsis in most children. PMID- 1289138 TI - Can retinoscopy be used to screen infants for amblyopia? A longitudinal study of refraction in the first year of life. AB - One hundred normal babies were refracted by two observers in a double-masked study within 24 hours of delivery and 30 minutes after instillation of 1% cyclopentolate. The procedure was repeated at 6 weeks, 3 months, 6 months and 1 year. At birth agreement between the two refractionists to within 1 dioptre spherical equivalent was 82%, rising to 94% at 1 year. Astigmatism of greater than 1 dioptre increased from 10% at birth to 42% at 6 months but decreased to 15% at 1 year. Myopia was uncommon (4%) but 80% of eyes were hypermetropic more than +2 dioptres and 25% more than +4 dioptres at birth, although these percentages decreased to 5% and 3% at 1 year. Anisometropia of more than 1 dioptre between the two eyes was uncommon but in the two cases where it persisted in the presence of high hypermetropia, reversible amblyopia was encountered in both cases. PMID- 1289139 TI - Standardised echography in the differential diagnosis of extraocular muscle enlargement. AB - Standardised echography is well documented for its use in the evaluation of enlarged extraocular muscles in orbital disease, but is still a largely underdeveloped imaging method in Britain. This paper demonstrates the technique of muscle ultrasound scanning and the characteristic echographic findings in a variety of extraocular muscle diseases, as illustrated by five case reports. The role of echography in the management of such cases is discussed. PMID- 1289140 TI - A prospective study examining the changes in factors that affect visual acuity following trabeculectomy. AB - Many patients report subjective changes in vision following trabeculectomy. In a prospective study of 16 eyes, we have tried to determine the causes of these visual changes. Ninety-four per cent of eyes showed a change in uncorrected Snellen acuity 1 week following surgery. This change was due to a myopic shift in refraction secondary to changes in the anterior chamber depth. A 1 mm change in anterior chamber depth results in approximately a 2 dioptre change in refractive sphere. Visual acuity starts to return to pre-operative levels by the third post operative week, from which point no eyes showed a deterioration in corrected acuity of more than one line of Snellen. The vertical corneal radius of curvature is reduced in the early post-operative period and there is a with-the-rule change in corneal astigmatism. This resolves over longer follow-up and the possible causes of this are discussed. No changes were noted in corneal thickness and there was no evidence of macular oedema over the follow-up period. Patients should be warned of these possible visual changes pre-operatively as many will have normal acuity prior to surgery. PMID- 1289141 TI - Fields, DVLC and panretinal photocoagulation. AB - Laser panretinal photocoagulation (PRP) reduces visual loss in proliferative diabetic retinopathy but decreases peripheral retinal function. The Driver and Vehicle Licensing Centre (DVLC) states that when a patient volunteers that he or she has had photocoagulation, a questionnaire will then be sent to the patient's diabetic physician who can refer the patient for formal field testing. Of 30 patients who had PRP, 15 failed DVLC visual field regulations using the Esterman binocular field test on the Humphrey field analyser. The failures were more likely to have had treatment with a xenon laser, but there was no difference between the groups as regards age, number of burns or whether an argon or diode laser was used. The patients who failed were more likely to be hypertensive (p = 0.04). Two patients with unilateral PRP could not meet the driving regulations because of other field defects. Diabetes itself causes field defects, and therefore even with small amounts of laser, formal field testing may be necessary. PMID- 1289142 TI - Comparison of small-incision phacoemulsification with standard extracapsular cataract surgery: post-operative astigmatism and visual recovery. AB - A prospective study compared post-operative astigmatism and visual acuity (corrected and uncorrected) following phacoemulsification and extracapsular surgery. Fifty eyes had implantation of a 7 mm diameter optic intraocular lens (IOL) following conventional extracapsular cataract extraction (ECCE) with a 10 mm corneal incision. Forty-seven eyes were implanted with a 5 x 6 mm optic IOL through a 5 mm scleral incision after phacoemulsification. Uncorrected visual acuity of 6/9 or better was achieved in 25% of eyes on the first day following phacoemulsification, 36% at 1 week and 57% at 12 weeks. These results (and also the best corrected acuity) were significantly better than those following ECCE. Less astigmatism was induced by phacoemulsification than extracapsular surgery, measured at all post-operative time intervals. PMID- 1289143 TI - Corneal autoimmunity in patients with peripheral ulcerative keratitis (PUK) in association with rheumatoid arthritis and Wegener's granulomatosis. AB - Serum antibodies to the cornea were investigated in patients with peripheral ulcerative keratitis (PUK) in isolation or in association with a systemic disease (rheumatoid arthritis or Wegener's granulomatosis). Indirect immunofluorescence on bovine corneal sections demonstrated that antibodies bound to epithelial antigens in two distinct patterns: a lattice-like pattern, probably staining intercellular membrane antigens, and a diffuse pattern covering the entire surface of the epithelium. Both patterns were associated with PUK rather than systemic disease whilst the presence of the lattice pattern was more associated with the onset of the PUK. Immunoblotting of sera to corneal epithelial protein extracts demonstrated that a number of corneal antigens were targeted by antibodies. Two antigens, 54 kDa and 70 kDa, were of particular interest. Antibodies to the 54 kDa antigen, the major corneal-specific antigen, were also detected by enzyme-linked immunosorbent assay (ELISA). Longitudinal studies showed that these antibodies often first occurred after an episode of PUK. Antibodies to the 70 kDa antigen were related to the Wegener's granulomatosis rather than the PUK. PMID- 1289144 TI - A morphological study of rabbit corneas after laser keratectomy. AB - We have examined the morphology of the collagen and proteoglycans in rabbit corneas that have undergone excimer laser photorefractive keratectomy using a clinical, 193 nm excimer laser. The photoablation was carried out to a stromal depth of 100 microns and a diameter of 6 mm. All ablated corneas developed a haze that was most intense between week 4 and week 8 and which showed no improvement after week 16. The corneas were stained with the cationic dye cuprolinic blue to visualise proteoglycans and were then processed for transmission electron microscopy. The ultrastructural location of proteoglycans (keratan sulphate and dermatan sulphate) was observed in the corneal wounds at different time intervals. Corneas that had undergone steroid treatment post-operatively were also examined. In the healing tissue proteoglycan filaments of abnormal size were observed, which became most prominent after 2 weeks. As healing progressed these abnormal filaments decreased but after 45 weeks some were still present, indicating that the proteoglycan content had not returned to normal. PMID- 1289145 TI - Immunocytochemical analysis of blood lymphocytes in uveitis. AB - We studied the surface expression of activation markers IL2-R, HLA-DR and CD45-RO on peripheral T-lymphocytes in two groups of patients (n = 26) with idiopathic uveoretinitis, compared with controls. Thirteen patients were analysed by alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry, which demonstrated a significant rise in expression of HLA-DR and IL2-R surface markers. Flow cytometric analysis was performed on a further 13 patients, which confirmed a significant rise in IL2-R expression in uveitis patients. Within this group systemic activation was confined to patients with idiopathic retinal vasculitis. Dual flow cytometry confirmed a CD4+,IL2--R+ T--lymphocyte phenotype. A further 4 patients with retinal vasculitis who had been treated with cyclosporin A demonstrated a 32% reduction in IL2-R expression over a 3-month period. Analysis of CD45-RO and CD5+ cells was found to be uninformative in this study. We have demonstrated activated peripheral lymphocytes in patients predominantly with retinal vasculitis, the significance of which is discussed. PMID- 1289146 TI - Plasminogen activator in human tears. AB - Measurements were made of the nature and levels of plasminogen activator in human tears using, as a model of inflammation, patients undergoing cataract surgery. Tissue plasminogen activator (t-PA) but not urokinase plasminogen activator (u PA) was found in tears. A wide variation in the range of t-PA in pre-operative tears was found. In those patients not receiving per-operative subconjunctival betamethasone a significant rise in t-PA was found in tears on the first post operative day over pre-operative levels. A significant fall was noted in those receiving per-operative subconjunctival betamethasone. PMID- 1289147 TI - A scoring method for Hess charts. AB - A new scoring system for Hess charts is described. Scores for both horizontal and vertical deviations are calculated from the displacement of individual points on the Hess chart, using weighting factors for the centre, inner and outer zones. The scoring system was validated in a group of 24 patients undergoing surgery for paralytic or restrictive strabismus. Subjective scores were obtained from patients both before and after corrective surgery, and corresponding Hess charts were scored using the new system. There was a good correlation between the changes in subjective and objective score. Our scoring system has applications in both research and clinical practice, allowing objective analysis of changes in muscle balance in a variety of motility disorders. PMID- 1289148 TI - Orbital inflammatory disease and bone destruction. PMID- 1289149 TI - A case of unique altitudinal distribution of a retinal contusion (Berlin's oedema) in a healthy teenager. PMID- 1289150 TI - Dangerous reflections during argon laser photocoagulation. PMID- 1289152 TI - Will the 21st century be dentistry's golden age? PMID- 1289151 TI - Complications of 5-fluorouracil after trabeculectomy. PMID- 1289153 TI - Experience with the Astra dental implant system. AB - The Astra Dental Implant System appears to be a relatively successful and economical method of osseointegration. This article lists its clinical components, explains how the system is fitted and discusses the preliminary results. PMID- 1289154 TI - Computer-aided diagnosis. AB - The author advocates the use of computers to increase the accuracy of diagnosis. Their ability to rapidly sift through large amounts of information and calculate probabilities quickly could provide a useful adjunct to human skills. PMID- 1289156 TI - Food and oral health: 2. Periodontium and oral mucosa. AB - Dental schools tend to teach only the rudiments of this subject and this does not provide a good basis for dentists to advise patients and combat the misinformation surrounding the topic. The first article in the two-part series examined nutrition as it applies to dental caries, while part two discusses some of the general principles of nutrition in relation to oral health, periodontal disease and the oral mucosa. PMID- 1289155 TI - Oral problems and the dentist's role in the management of paediatric oncology patients. AB - Child cancer patients require a great deal of intensive treatment and support. This paper provides an account of the dental problems a practitioner will encounter with these children and discusses how they may be managed. PMID- 1289157 TI - Prevention in orthodontics--a review. AB - Increasing numbers of patients are being orthodontically treated by specialist and general dental practitioners, after postgraduate courses and clinical assistantships. The potential for iatrogenic damage to the teeth and supporting structures has, therefore, also increased. This paper examines these problems and outlines measures for their prevention. PMID- 1289159 TI - The Faculty of General Dental Practitioners (UK) PMID- 1289158 TI - Fusion of mandibular third and supernumerary fourth molars. AB - Fusion of the permanent molars is a relatively uncommon dental anomaly. In this article, a case of fusion of a symptomatic mandibular third molar with a supernumerary fourth molar is reported. The differentiation with other forms of 'double teeth' is explained and the possibility of the initial panoramic radiograph view being misinterpreted as an artefact is discussed. PMID- 1289160 TI - Guided tissue regeneration--why, when and how? AB - Chronic periodontitis results in the destruction of the collagen fibre attachment to cementum, apical migration of the epithelial attachment, contamination of the exposed root surface by plaque and loss of alveolar bone. Regeneration can be defined as the restitution of lost tissues to a state which existed before destruction. As such, it is an ultimate and ideal goal and in most circumstances is currently beyond our capabilities. However, research in periodontology over the last 10 years or so has made considerable advances and is perhaps unique in proposing a new and fundamental treatment modality--guided tissue regeneration. PMID- 1289161 TI - Orthodontic/restorative interface. AB - There have been many advances in orthodontic and restorative procedures. These can be combined to provide a very powerful tool in providing the optimum results. This article describes when a combined approach would be appropriate and discusses how the various problems are overcome. PMID- 1289162 TI - Some problems with anticoagulants in dental surgery. AB - Anticoagulants have been used to reduce the risk of embolic and thrombotic complications in patients at risk since the discovery of the coumarin drug warfarin sodium in 1941. Since then, both the spectrum of disease for which anticoagulation is recommended and the range of anticoagulants has widened. In addition to treatment with conventional anticoagulant drugs, many patients nowadays have an additional bleeding defect due to the therapeutic use of daily low-dose aspirin therapy, either alone or in combination with other drugs. The aim of this report is to highlight some of the important aspects of anticoagulant therapy and its relevance to dental treatment. PMID- 1289163 TI - Selected issues on care and management of the ageing patient: 1. Utilization and decision making. AB - The elderly are a vulnerable and expanding group of patients who are retaining their teeth longer. Even simple dental care in these people can become invasive and require the use of a local anaesthetic. Part 1 assesses the factors which may influence the ability of the patient to receive treatment and establishes treatment priorities. It also describes the particular problems that may arise when dealing with the elderly and indicates the adjustments of a practice which would help in the care of these patients. Part 2 will discuss prevention and treatment. PMID- 1289164 TI - Continuing education--an approach to organizing a course. AB - The importance of continued education for the general dental practitioner is being increasingly emphasized. This paper describes the review of a prosthetic dentistry course which endeavoured to involve local practitioners to increase its appeal and relevance. PMID- 1289165 TI - Conservative treatment for anterior dislocation of the meniscus. AB - Anterior dislocation of the meniscus is classified as an internal derangement of the temporomandibular joint (TMI). The pathogenesis and clinical syndromes of anterior dislocation have been described fairly frequently. Conservative treatment for this painful, clicking joint is the treatment of choice. This article presents the results of the simple conservative treatment of a case with clinical manifestation which are classical as an early stage of anterior dislocation without reduction of the meniscus. PMID- 1289166 TI - Plasma and tissue hormones in the dog after administration of the prostaglandin analogue, misoprostol. AB - Dogs were given a prostaglandin analogue, misoprostol, at a dose that significantly increases gastrointestinal epithelial cell proliferation. Both basal and postprandial concentrations of gastrin were significantly higher in the misoprostol-treated dogs and more than doubled after the meal in both the controls and in the test group. Plasma enteroglucagon, cholecystokinin, insulin and glucose-dependent insulinotrophic peptide all increased postprandially, with no effect of misoprostol. Tissue concentrations of bombesin, gastrin and somatostatin were unaffected by misoprostol, but the fundic glucagon-like immunoreactivity was significantly increased. Thus high doses of misoprostol have only minor effects on gastrointestinal regulatory peptides, suggesting that the trophic effect of prostaglandins on the intestinal tract may be direct. PMID- 1289167 TI - Two weeks of oral synthetic E2 prostaglandin (Enprostil) improves the intestinal morphological but not the absorptive response in the rat to abdominal irradiation. AB - Enprostil, a synthetic E2 prostaglandin, was administered in a dose of 5 micrograms/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal's body weight, but does not prevent the malabsorption of glucose. PMID- 1289168 TI - Effect of zinc sulfate and acetylcysteine on experimental gastric ulcer: in vitro study. AB - A small ulcer produced in vitro by monopolar electrocoagulation on endoscopically obtained human antral biopsies and incubated in Trowel T-8 medium at 37 degrees C for 8 h has many histologic features of chronic gastric ulcer in man. Zinc sulfate and acetylcysteine in low concentrations had a significant healing effect in this ulcer model. Since the beneficial effect of zinc sulfate and acetylcysteine was counteracted by N-ethylmaleimide, a known blocker of sulfhydryl compounds, the beneficial effect of these two compounds probably was mediated through sulfhydryl compounds. Using special stain, N-(4 aminophenyl)maleimide, the sulfhydryl groups were localized in the epithelial cells of the surface layer and gastric glands. PMID- 1289169 TI - Effect of chronic ethanol feeding on factors leading to inappropriate intrapancreatic activation of zymogens in the rat pancreas. AB - In rats fed control and ethanol-containing Lieber-DeCarli diets for a period of 12 months, the bile did not contain any enterokinase, the pancreatic juice did not contain any plasmin or thrombin, but in animals fed high fat diet with ethanol, trypsinogen and chymotrypsinogen were significantly increased and trypsin inhibitor decreased. In the tissue, free trypsin and cathepsin B were increased. Composite profile of trypsinogen in gel segments obtained from the pancreatic juice and the tissue showed higher peaks of cationic and anionic variants of trypsinogen in animals fed ethanol. There was no evidence of mesotrypsinogen or of enzyme Y in the juice or the tissue. These studies show that serine proteases and cathepsin B may play a major role in the pathobiology of alcoholic pancreatitis. PMID- 1289170 TI - Effects of gastric fundectomy and antrectomy on the colonic mucosa in the hamster. AB - The effects of gastric fundectomy and antrectomy on the colonic mucosa were studied in hamsters over 5 and 25 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly increased after fundectomy and significantly decreased after antrectomy. Five days after fundectomy, there was a significant increase in scintigraphically determined colonic tissue [3H] thymidine uptake and [3H]-thymidine labeling index of goblet cells, both of which were reduced 5 days after antrectomy. After fundectomy, the labeling index was maximal in differentiating-proliferative cells in the midportion of the colonic crypts, whereas the labeling index of the immature proliferative cells at the base of the crypts did not differ from that in the controls. On day 25, the crypt size and the number and percentage of goblet cells in the crypts were significantly increased in fundectomized animals. The number and percentage of goblet cells in antrectomized animals were significantly reduced on day 25. It is concluded that fundectomy in the hamster induces colonic mucosal hyperplasia with goblet cell proliferation, whereas antrectomy leads to retardation of colonic goblet cell proliferation. PMID- 1289171 TI - Effects of phosphatidylcholine and phosphatidylinositol on acetic-acid-induced colitis in the rat. AB - The therapeutic effects of exogenous phosphatidylcholine and phosphatidylinositol on acetic acid-induced colitis in rats were evaluated. A uniform colitis developed 4 days after instillation of 4% acetic acid for 15 s in an excluded colonic segment, also resulting in a 6-fold increase in mucosal permeability. Instillation of 12.5 mg phosphatidylcholine once daily from the day after acetic acid instillation and for the following 2 days prevented partially the development of colitis causing partial mucosal restoration. By increasing the phosphatidylcholine dose to 25 and 50 mg, a better preventive effect was achieved. By starting the phosphatidylcholine instillation immediately after the acetic acid exposure, almost complete prevention of the colitis could be obtained. Similarly, 50 mg phosphatidylinositol in each instillation with the first administration immediately after acetic acid administration resulted in complete prevention of the colitis and a significant decrease in mucosal permeability expressed as a plasma exudation into the colonic lumen. Similar results were obtained when phosphatidylcholine was administered immediately after acetic acid, but the drug then had to be applied twice daily. In contrast, a single application of the same total dose (150 mg) of the two different phospholipids, either 30 min before or immediately after acetic acid administration, could not prevent the development of colitis. It is concluded that both phosphatidylcholine and phosphatidylinositol have a therapeutic effect on the development of acetic acid-induced colitis in the rat. PMID- 1289172 TI - Effect of teprenone on acute gastric mucosal lesions induced by cold-restraint stress. AB - The effects of intragastric administration of teprenone on acute gastric mucosal lesions induced by cold-restraint stress was investigated using a model of obstructive jaundice. Rats received teprenone 200 mg/kg/day for a week before stress; nontreated rats served as controls. Teprenone suppressed stress-induced depressions in defensive factors (blood flow, transmucosal potential difference, hexosamine content and lectin staining of carbohydrate residues) and suppressed increases in lesion-enhancing factors (gastric mucosal lysosomal enzyme activity and thiobarbituric acid reactants showing lipid peroxidation). Intragastric pH did not change significantly with teprenone but the ulcer index decreased. These results showed that teprenone protects gastric mucosa against stress, even in the presence of obstructive jaundice. PMID- 1289173 TI - Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial. AB - According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain. PMID- 1289174 TI - Study of the effect of neurotensin on meal- and cerulein-induced gallbladder contraction. AB - We studied the effect of a low dose of neurotensin (2.5 pmol/kg/min) on meal- and cerulein-induced gallbladder contraction in 11 healthy volunteers by means of real-time ultrasonography. Ingestion of a meal caused a significant reduction in gallbladder volume which reached a maximum of 57 +/- 2% of the basal value at 60 min after the meal. The infusion of neurotensin caused a slight but not significant attenuation of the contractile response of the gallbladder to the meal (maximal reduction of 49 +/- 6%). Increasing doses of cerulein (10, 20 and 40 ng/kg/h, for 30 min at each dose) caused progressive reductions in gallbladder volume of 18 +/- 5, 72 +/- 5 and 89 +/- 4% with the three respective doses of cerulein used. The simultaneous administration of neurotensin did not significantly modify the gallbladder response to cerulein. The results indicate that neurotensin, at a dose of 2.5 pmol/kg/min, does not influence the gallbladder contraction stimulated by food or cerulein. PMID- 1289175 TI - Sucralfate, ranitidine and no treatment in gastric ulcer management--a multicenter, prospective, randomized, 24-month follow-up with a study of risk factors of relapse. GISU (Interdisciplinary Group for Ulcer Study). AB - This multicenter, prospective, randomized, open, long-term study compares sucralfate (2 g daily) with ranitidine (150 mg daily) and no treatment in gastric ulcer (GU). We report the results of the second year of a scheduled 3-year follow up, the outcome of the 1st year has been reported earlier. The 24-month follow-up was completed by 142 patients who were continuously either treated with the drug randomly assigned at the beginning of the study or left untreated (i.e. 32 patients took 150 mg ranitidine at bedtime, 29 took 1 g sucralfate twice daily and 81 were left untreated, 23 of whom came from the ranitidine group, 19 from the sucralfate group and 39 from the untreated group). Seven patients dropped out and 26 subjects relapsed (5 under ranitidine, 4 under sucralfate and 17 untreated cases). Ranitidine versus previous ranitidine, sucralfate versus previous sucralfate and each one versus no treatment showed comparable relapse rates. An additional study, using Cox's models, showed that three variables have a significant correlation with relapse during the 1st year of follow-up: therapy carried out (p = 0.0025), symptoms (p = 0.0047) and family history of ulcer (p = 0.0392). In conclusion, both ranitidine 150 mg and sucralfate 2 g proved effective in reducing GU relapse as compared with no treatment, an effect which does not seem to persist during the 2nd year of therapy, when the 'no treatment' option may be taken into account. PMID- 1289176 TI - Time course study on the action of 5-hydroxytryptamine on gastric secretion and mucosal blood flow and on ethanol-induced gastric mucosal damage in rats. AB - The effects of 5-hydroxytryptamine (5-HT; given i.p. in doses of 1 or 10 mg/kg) on gastric secretion and mucosal blood flow (GMBF) and on ethanol-induced gastric mucosal damage were studied in rats over a period of 30-450 min. The blood pressure was also examined, in relation to the changes in GMBF. 5-HT, 10 mg/kg, given 30 min before ethanol administration markedly worsened lesion formation and this potentiating action was present for a further 90 min; a significant protective effect was seen only at 450 min after 5-HT injection. The lower dose of 5-HT, 1 mg/kg, did not affect the severity of gastric damage. 5-HT (10 mg/kg) also decreased GMBF at 30 min after injection and this lasted up to the end of 120 min, but the depressive action of ethanol on GMBF was reversed at 450 min. The basal gastric secretory volume was depressed from 30 to 120 min but acid output fell from 75 to 120 min after the higher dose of 5-HT; this reduction of acid secretion was followed by an increase from 360 to 450 min. 5-HT decreased the mean blood pressure in a dose- and time-dependent manner. The heart rate was unaffected by either dose level of 5-HT. The present study not only demonstrates the ulcerogenic action of 5-HT but also the protective nature of the amine. The reduction in secretory volume and lesion formation, but not acid secretion, seems to be related to GMBF depression, whereas the protective action depends on the maintenance of GMBF. PMID- 1289177 TI - Putrescine uptake and metabolism in isolated rat pancreatic acini. AB - In addition to de novo synthesis, polyamine uptake is one of the major mechanisms in the regulation of intracellular polyamine concentrations. The aim of the present study was to investigate the uptake of putrescine (PUT) in isolated rat pancreatic acini and its further metabolic transformation. PUT accumulation was nearly linear over 60 min, showed saturation kinetics with an apparent Km of 3 x 10(-5) M and a Vmax of 346 pmol [14C]-PUT/min/mg DNA and decreased with decreasing temperature. Potassium cyanide (KCN) and dinitrophenol (DNP) inhibited PUT uptake. In the absence of a transmembrane Na+ gradient, PUT uptake decreased by 50%. After 60 min of incubation, 31% of the accumulated [14C]-PUT was metabolized. PUT uptake was stimulated by several amino acids, except for lysine, by decreasing the apparent Km for PUT uptake. PUT accumulation was reduced by spermidine (0.1 mM) by about 90%. Acetylated polyamines had only a minor effect. The release of radioactive material from prelabelled acini was only 10-20% after 90 min. PMID- 1289178 TI - Risk of ulceration with long-term indomethacin: endoscopic and histological changes in upper gastro-intestinal mucosa. AB - Twenty patients taking long-term indomethacin were chosen for the study because all had a normal endoscopic examination; biopsies, however, from the oesophagus, gastric antrum and duodenal bulb revealed histological inflammation in all patients in at least one site. After 8 weeks during which indomethacin therapy was continued, a further endoscopy revealed lesions in 5 patients--peptic ulcer in 3 and erosions in 2--but only 1 of these had any change in gastro-intestinal symptoms. Irrespective of whether mucosal lesions are seen on endoscopy in patients established on non-steroidal anti-inflammatory drug therapy, they remain in danger of developing both ulcers and erosions which are likely to be asymptomatic. At no time can one justifiably feel this patient group is not at risk of peptic ulceration. PMID- 1289179 TI - Fecal fat concentration in the screening of steatorrhea. AB - We studied if the fecal fat concentration as measured by the near infrared reflectance analysis in a spot sample is an acceptable screening test for malabsorption. This measurement was compared with the more complex fat balance in 120 patients with a suspected malabsorption [53 with chronic pancreatic disorders (CP), 67 with other digestive disorders (nCP)]. The fecal fat concentration proved to be well correlated with steatorrhea in CP (r = 0.86) but not in nCP (r = 0.35). A fat concentration of 9 g% had a sensitivity and a specificity for steatorrhea of 88.8% and of 97.1% in CP, but only of 53.8% and of 94.4% respectively in nCP. The fecal fat concentration was significantly higher in CP than in nCP, even considering patients with steatorrhea only; however, the overlap between the two groups was too high to suggest a clinical usefulness of this test in the differential diagnosis of steatorrheas. It is concluded that the fat concentration in a small sample, easily obtained also in outpatients, is useful in the selection of patients with chronic pancreatitis to submit to a proper fat balance study. PMID- 1289180 TI - Higher erythropoietin secretion in response to cobaltous chloride in post-hypoxic than in hypertransfused polycythemic mice. AB - BACKGROUND: We have shown previously that both erythrocyte production rate (EPR) and plasma erythropoietin (EPO) levels in response to hypoxia or to compounds able to stimulate EPO secretion are very much higher in post-hypoxic (PH) than in hypertransfused (HT) polycythemic mice with similar levels of hematocrit. Since it has been demonstrated that cobalt (Co) treatment rises renal EPO-mRNA and increases plasma EPO levels, the present study was conducted to determine whether there is a difference between PH and HT mice in relation to the erythropoietic response to Co and whether the stimulatory effect of Co on EPO secretion can be blunted by polycythemia. METHODS: Adult female mice of the CF-1 strain were made polycythemic by either exposing them to 270 h of discontinuous hypoxia (18 h/d) in a hypobaric chamber maintained at 456 hPA (PH mice) or by injecting them with 0.8 ml of washed packed red cells on two consecutive days (HT mice). Measurement of the erythrocyte production rate (EPR) was made by RBC-59Fe uptake. Plasma EPO concentration was determined by RIA. Cobalt chloride (CoC12) was dissolved in saline and injected in doses of 4 and 8 umoles/mouse. Recombinant human EPO (HEMAX 4000, Bio Sidus SA, Argentina) was dissolved in PBS + albumin to the desired concentration. RESULTS: By comparison with the corresponding dose regression line for rHu-EPO, it was estimated that the responses (EPR) (measured as RBC-59Fe incorporation) of PH mice to sc injections of 4 and 8 umoles of CoC12 were equivalent to 95 and 145 mU of rHu-EPO, respectively. The response of HT mice to 4 umoles of the drug was not detectable. At the upper dose level, the response was equivalent to 52 mU of rHuEPO. Plasma immunoreactive EPO (iEPO) titers 12 h after COC12 (8 umoles) were not significantly different between normocythemic and PH mice. The observed values were significantly higher than those found in HT mice. DISCUSSION: These findings demonstrate that EPO production in response to COC12 is depressed by polycythemia when induced by transfusion but not when induced by chronic exposure to hypobaric hypoxia. They also confirm, but not explain the nature of the conditioning effect of exposure to hypoxia which makes the mechanism controlling EPO secretion either more sensitive to EPO-secreting stimuli or unable to recognize the polycythemic state. PMID- 1289181 TI - Hereditary spherocytosis (HS) due to loss of anion exchange transporter. AB - BACKGROUND: Hereditary spherocytosis encompasses a heterogenous group of inherited disorders due to alteration of r.b.c. surface/volume ratio. Spectrin deficiency is the most common observed defect. We analyzed a case of HS associated with band 3 deficiency without spectrin reduction. METHODS: In the study of a family originating from southern Italy, we show that a 20% deficiency of band 3 with normal spectrin content may be responsible for dominantly inherited hereditary spherocytosis (HS). The proband is a 12 years old girl consulting for jaundice, chronic anaemia and splenomegaly. Her mother had a similar haematologic phenotype. RESULTS: Electrophoretic analysis of erythrocyte membrane proteins showed a deficiency in band 3 protein. Band 3 protein chymotryptic fragments, deglycosylated band 3, and its isolated cytoplasmic domain, all displayed normal electrophoretic migrations. Furthermore, the tryptic peptides profile of the cytoplasmic domain of the protein did not demonstrate any abnormality, nor did the amino acid composition of the peptides. Analysis of the membrane proteins during erythrocyte ageing, evaluated in density-fractionated red cells, showed that band 3 content was normal in the lighter fraction, whereas in the denser fraction band 3 deficiency was more pronounced than in membranes from non fractionated red blood cells. CONCLUSIONS: This case describes HS due to anion exchange transporter deficiency. Our results on fractioned red cells support the hypothesis that the defect was probably due to a band 3 protein loss during cell ageing and not to a primitive quantitative defect. PMID- 1289182 TI - High-dose cyclophosphamide followed by GM-CSF is a safe and effective procedure for the recruitment of trilineage circulating progenitor cells. AB - BACKGROUND: Several methods for the recruitment of circulating progenitor cells (CPC) to be used for hemopoietic rescue after myeloablative therapy have been described. The present study was designed to verify the effectiveness and safeness of one of such procedures, involving the administration of high-dose cyclophosphamide (HD-CTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Eight tumor patients were treated with HD-CTX (7 g/m2), followed by GM-CSF (7 mcg/Kg/day, continuous infusion) from day +2 to the completion of leukocyte recovery, when aphereses for CPC harvesting were performed. CPC were evaluated by clonogenic assay for granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming units (CFU-Meg) and erythrocyte burst-forming units (BFU-E) before therapy as well as during the hemopoietic recovery. RESULTS: In each patient, a significant increase of trilineage CPC was observed, at a mean of 14 days from HD-CTX, with peak increment of 224, 268 and 230-fold for CFU-GM, CFU-Meg and BFU-E respectively. The mean duration of leukocyte count < or = 0.5 x 10(9)/l was 6.6 days, with severe thrombocytopenia (grade 4 WHO) lasting 2.8 days in 5 patients. GM-CSF infusion was well tolerated without any need for dose reduction or discontinuation. CONCLUSION: The administration of HD-CTX and GM-CSF induces a significant enhancement of CPC including CFU-Meg other than CFU-GM and BFU-E. The procedure is suitable for the recruitment of CPC in patients with CTX sensitive tumors. PMID- 1289183 TI - Limiting dilution analysis of IL-2 producing cells: I. Studies of normal human peripheral blood. AB - BACKGROUND: After marrow transplantation, the interaction of helper T lymphocytes from the donor with the patient alloantigens leads to cellular activation and release of IL-2 as initial events of the graft versus host reaction. A method for assessing the size of the pool containing allospecific helper T cells capable of producing IL-2 could be applied in the selection of better donors for marrow transplantation. MATERIAL AND METHODS: PBMC are added to replicate sets of wells each containing various amounts of EBV-LCL cells and PHA. After culture for some days the supernatant is removed from each well and added to IL-2 dependent CTLL-2 line. The proliferation of the CTLL-2 line is assessed by pulse labeling with 3H thimidine. The precursor frequency of cell capable of producing IL-2 per ml/blood is estimated from the minimum X2 regression of the function of non-responding wells plotted as logarithmic function of the number of PBMC added per well. RESULTS: Approximately 30-40% of PBMC are found to produce IL-2 under the following conditions in culture: the optimal PHA concentration is 1.25 micrograms/ml, the optimal number of stimulator EBV-LCL cells is 1 x 10(3) and 3 days of culture are required. CONCLUSION: Here we report a rapid and quantitative technique of limiting dilution analysis that can estimate the frequency of peripheral blood mononuclear cells capable of secreting interleukin-2 following interaction with specific alloantigen. PMID- 1289184 TI - A pilot External Quality Assessment Scheme for haemocytometry in Italy. AB - BACKGROUND: An Italian EQA scheme for haemocytometry, organized by the Istituto Superiore di Sanita, has been active for about five years (1984-1989). The aims of this programme were to evaluate the state of the art and to introduce in Italy a scheme recommended by ICSH. N. 126 public laboratories from different provinces joined voluntarily the programme and trials for haemoglobinometry (A01, A02), full blood count (B01-B08) and platelet count (D01-D03) were performed. METHODS: Materials for testing consisted of blood lysate, preserved blood preparation containing native red cells and pseudoleukocytes, suspension of fixed platelets. The performances of laboratories was evaluated by consensus values (median, mean and standard deviation) and individual deviation index. RESULTS: The instrument survey demonstrated that fully automated systems had the highest frequency. Non Gaussian distributions of results were often obtained and this was particularly true for WBC, PLT and MCV. The overall variability was lower than 5.5% for Hb, RBC and MCH and lower than 9.3% for other erythrocyte parameters; WBC and PLT counts displayed a higher dispersion (CV* = 9.8% and 25.4%); the spreading of results was strongly reduced in the homogeneous group of Coulter counters. In the course of the programme CV*s didn't show any relevant modification, a steady state performance being apparent. As regards the nature of variability, the random component was prevalent for all parameters, with the exception of MCV. CONCLUSIONS: This pilot programme allowed to demonstrate the practicability of a national EQAS for haemocytometry according to the ICSH guidelines. Materials for testing showed acceptable stability, homogeneity and commutability. As regards analytical equipment as well as analytical variability, hospital centers participating in these EQA trials were comparable with laboratories taking part in similar EQAS of other European countries. PMID- 1289185 TI - ANLL patients with normal karyotype are not a homogeneous prognostic group. AB - BACKGROUND AND METHODS: Karyotype in ANLL is referred as an independent prognostic factor. The prognosis of diploid ANLL subjects has been defined as "good" by some authors, or, more recently, "intermediate" by others. This is a retrospective study on 30 consecutive heavy treated ANLL diploid patients with the aim to make a correlation among age, normal karyotype and response. Chromosomal banding studies were performed at presentation with GTG technique. Diploid patients were divided into two age groups < 60 years (17 cases) and > or = 60 (13 cases). Data were analyzed by NCSS software. RESULTS AND CONCLUSIONS: CR rate for the two diploid age groups was 94% and 38% respectively (p = 0.002). Median DFS and overall survival were 14.4 and 23.3 months, 4 and 5 months for the two subgroups respectively: these data were not statistically significative. The probability of achieving CR was not affected by blood counts and Karnofsky performance status on admission, but only by age. Though ANLL patients with the same karyotype have the same course regardless of other prognostic factors, this does not occur in our series of diploid patients. We suggest that a normal karyotype, at least as defined with the GTG technique, does not characterize a homogeneous group of patient. Heterogeneity in this group might be due to submicroscopic or molecular genetic changes; it can enhance the age as prognostic factor. PMID- 1289186 TI - Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia. AB - BACKGROUND: Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS: In a pilot study, we administered recombinant human erythropoietin (rHuEPO) to twelve patients with solid tumours and secondary anaemia. rHuEPO was given subcutaneously 5 d per week at escalating doses (75 to 150 U/kg per day): the aim of treatment was a Hb level > or = 10 g/dl without blood transfusion. We evaluated endogenous EPO production through serum EPO levels and erythroid marrow activity by means of serum transferrin receptor (TfR). RESULTS: Six out of 12 subjects had defective endogenous EPO production. All patients but two responded to treatment with steady increases in Hb levels above 10 g/dl, and the median dose of rHuEPO required for correction of anaemia was 75 U/kg. Response was associated with an early increase in serum TfR. Six patients developed functional iron deficiency and required iron supplementation to obtain response. Treatment improved functional ability in 4/10 responders. CONCLUSIONS: Subcutaneous rHuEPO can stimulate erythroid marrow activity in cancer anaemia, even in patients with advanced disease, and marrow response can be adequately monitored by serum TfR. Functional iron deficiency as a cause of nonresponse to rHuEPO is frequent in these patients and may require parenteral iron administration. Although erythropoietin can improve the anaemia of cancer, the decision to treat should be individualised for each patient, looking more at the quality of life and cost effectiveness than at cosmetic increases in the haemoglobin level. PMID- 1289187 TI - alpha-Interferon treatment of chronic hepatitis C in young patients with homozygous beta-thalassemia. AB - BACKGROUND: Chronic infection with the hepatitis C virus (HCV) and iron overload are the main causes of chronic liver disease in subjects with homozygous beta thalassemia (HBT). Iron overload can be counteracted by intensive chelation. alpha-interferon reduces viremia and necroinflammation in patients with chronic HCV hepatitis. METHODS: To assess the effectiveness and safety of alpha 2b Interferon (IFN), we enrolled in an open pilot trial of treatment 12 patients with HBT and biopsy-proven anti-HCV positive chronic hepatitis. IFN was given at a dose of 5 MU/m2 thrice weekly for 8 weeks, then 3 MU/m2 thrice weekly for 18 weeks. Patients were followed up to 24 months after stopping treatment when a second liver biopsy was performed in subjects with sustained response (normal ALT during follow-up). RESULTS: Two patients discontinued IFN at 7 weeks because of haemolytic anemia and one after 8 weeks due to persistent fever. Among 9 subjects completing the protocol, 5 normalized ALT while on treatment and a further 2 within two months after stopping IFN. A sustained response was obtained altogether in 5 patients, since ALT relapsed in 2 responders. None of the 3 subjects who discontinued IFN and of the 2 patients who did not respond to treatment normalized ALT over a 24 months follow-up. Post-treatment liver histology in long-term responders showed a reduction of portal, periportal and lobular necroinflammation, while siderosis was essentially unchanged. CONCLUSIONS: Although the pattern of response to IFN in HCV-infected subjects with HBT might differ from that of non-thalassemics, due to peculiar side effects and delayed response, the drug appears to be effective and deserves further investigation. PMID- 1289188 TI - Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis. AB - A patient with transfusion-dependent thalassemia was undergoing home intravenous desferrioxamine (DFX) treatment by means of a totally implanted system because of his poor compliance with the nightly subcutaneous therapy. Due to an accidental malfunctioning of the infusion pump, the patient was inadvertently administered a toxic dosage of the drug which caused renal insufficiency. Given the progressive deterioration of the symptoms and of the laboratory values, despite adequate medical treatment, a decision was made to introduce haemodialytical therapy in order to remove the drug and therapy reduce the nephrotoxicity. From the results obtained, haemodialysis can therefore be suggested as a useful therapy in rare cases of progressive acute renal failure caused by desferrioxamine. PMID- 1289189 TI - Antiphospholipid antibodies and splenic thrombosis in a patient with idiopathic myelofibrosis (antiphospholipid antibodies and thrombosis). AB - A case of idiopathic myelofibrosis and hepatosplenic myeloid metaplasia associated with antiphospholipids antibodies is described. The patient developed a lethal complete splenic vein thrombosis in spite of an intravenously heparin treatment had been started soon after a clinical pattern of "acute abdomen". PMID- 1289190 TI - Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas. AB - Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622). PMID- 1289191 TI - Cutaneous involvement of systemic fungal infections in neutropenic patients. AB - Skin nodules can be the first evidence of a disseminated fungal infection in febrile neutropenic patients. We present our experience in the diagnosis of this clinical problem in five patients treated for serious hematologic conditions in our Service. There were two cases of Candida sp., two of Fusarium sp., and one of Trichosporon sp.. The immediate assessment of any suspicious lesion, including a biopsy of the lesion for microbiological and histopathologic examinations, will usually lead to the correct diagnosis. PMID- 1289192 TI - Alpha interferon as first line therapy for angioimmunoblastic lymphoadenopathy. Possible value of DR+ cells in monitoring therapeutical response. PMID- 1289193 TI - Thrombotic thrombocytopenic purpura developed during ticlopidine therapy. PMID- 1289194 TI - [Radical prostatectomy--experience with 50 patients]. AB - Between 1986-1991 we treated 50 men with adenocarcinoma of the prostate by radical prostatectomy. Ages ranged from 44-74 and clinical stages were A-C. Follow-up lasted 1-63 months (mean 15.1) and was designed to rule out recurrence and/or spread of the disease and to evaluate quality of life. The rate of complications was low, the postoperative course short and uneventful, and there was preservation of urinary continence in 96% and of potency in 10.2%. As compared with radiotherapy, surgery gave superior results and is recommended. PMID- 1289195 TI - [Percutaneous endoscopic gastrostomy]. AB - Although percutaneous endoscopic gastrostomy (PEG) for feeding purposes has been in use for the past 10-12 years, many practitioners are unaware of this option. We describe 10 patients who underwent PEG with only 1 major, but nonfatal, complication. We stress that PEG is indicated for those who cannot swallow, and is safe, easy to perform, and a relatively cheap procedure. It is therefore a useful substitute for surgical gastrostomy. PMID- 1289196 TI - [Pneumatic-retinopexy scleral buckling for retinal detachment]. AB - 30 eyes with rhegmatogenous retinal detachment due to retinal tear at the upper half of the circumference or due to a macular hole underwent SF6 gas injection into the vitreous. In 25 eyes (83%) the retina had re-attached 1-2 days following the injection and the tear was then photocoagulated. Final visual acuity was 6/12 or better in 13 eyes, 6/15-6/20 in 4 eyes, 6/30-6/60 in 8 eyes and less than 6/60 in 5 eyes, 3 of which had a macular hole. There was no morbidity or irritation compared to conventional scleral buckling, and the functional results were better. 4 of the 5 failures underwent successful surgery. In only 1 eye the retina could not be attached by surgery. Pneumatic retinopexy can substitute for surgery in selected cases of retinal detachment. PMID- 1289197 TI - [Cimetidine hepatitis]. AB - A 41-year-old man with rheumatoid arthritis developed severe acute hepatitis 3 days after starting cimetidine for duodenal ulcer. Other causes were ruled out and he recovered after cimetidine was discontinued. Mild transient elevations of hepatic enzymes have been reported in 3.6% of patients taking cimetidine. However, only 12 cases of severe acute hepatitis associated with cimetidine, mostly secondary to idiosyncrasy, have been reported in the English literature. This rare but serious complication of cimetidine should be kept in mind. PMID- 1289198 TI - [Transient hyperphosphatasemia of infancy]. AB - Transient hyperphosphatasemia of infancy was diagnosed in 4 children hospitalized during a 6-month period (0.3% of all hospitalized children). The characteristic features of this disorder are: 1. elevation of serum alkaline phosphatase (of both liver and bone origin) up to 3-30 times the upper limit of normal for age (usually discovered during intercurrent infection); 2. return of the serum alkaline phosphatase to normal in a few weeks; 3. no residual clinical or laboratory evidence of bone or liver disease. The child is usually less than 5 years old. Recognition of the benign nature of this disorder prevents extensive laboratory workup and unnecessary anxiety. PMID- 1289199 TI - [Jacuzzi-immersion for obstetric analgesia]. AB - The effect of immersion in a jacuzzi in relieving labor pains, and on cervical dilatation was examined in 40 parturients. They were immersed in the jacuzzi during labor for an average of 25.5 minutes. Labor pains decreased during immersion by 2.59 degrees (scale of 0-10) compared with an average increase in labor pains of 0.25 degrees in 40 control women who were not immersed (p < 0.01). The cervical opening increased during immersion by an average of 1.5 cm in the test group, compared with 0.3 cm in the controls (p < 0.01). Immersion in a jacuzzi during labor is apparently associated with analgesia and accelerated cervical dilatation. PMID- 1289200 TI - [Subcutaneous emphysema complicating laparoscopic cholecystectomy]. AB - Laparoscopy using carbon dioxide has been a standard gynecological procedure for many years. During the past 3 years, it has become commonly used in general surgery as well. Laparoscopic cholecystectomy is rapidly spreading world-wide. Although minor and major complications have been attributed to this procedure, their frequency is low. We report a case of subcutaneous emphysema following laparoscopic cholecystectomy. PMID- 1289201 TI - [Aortocaval fistula]. AB - Aortocaval fistula is a rare phenomenon which has both acute and chronic clinical presentations. Its diagnosis and treatment are difficult and it presents a surgical challenge of the first degree, requiring intensive perioperative care. A patient with an aortocaval fistula is described. It was found during emergency operation for a ruptured abdominal aortic aneurysm. PMID- 1289202 TI - [Induction of experimental SLE and antiphospholipid syndrome models in naive mice]. PMID- 1289203 TI - [New attitudes to pain control in multiple myeloma]. PMID- 1289204 TI - [Specific immunotherapy in allergic bronchial asthma]. PMID- 1289205 TI - [Osteoporosis and physical activity]. PMID- 1289206 TI - [Pain and dysfunction of the temporomandibular joint: etiology and treatment]. PMID- 1289207 TI - [Toxic epidermal necrolysis]. PMID- 1289208 TI - [Fractures of the temporomandibular joint]. PMID- 1289209 TI - [Diagnosis and treatment dilemmas in laryngotracheal trauma]. PMID- 1289210 TI - [Tachycardia]. PMID- 1289211 TI - [Radical prostatectomy]. PMID- 1289212 TI - [The cause of autoimmune disease?]. PMID- 1289213 TI - Management of hypertrophic cardiomyopathy. PMID- 1289215 TI - Balloon angioplasty for native aortic coarctation. AB - From May 1987 to August 1990, eighteen patients underwent balloon angioplasty for native aortic coarctation. The age of the patients ranged from four to fifty six years (mean age 17.5 years). The procedure was successful in all cases with a reduction in the peak gradient across the coarctation from 61 +/- 19 mm Hg to 11.7 +/- 8.1 mmHg (p < 0.05). The coarcted segment increased from 4.5 +/- 1.9 mm to 10.7 +/- 3.9 mm (p < 0.05). Peak gradient at six to twelve months follow up, obtained in ten patients, was 19.8 +/- 10.1 mmHg (p = NS). There were no life threatening complications, although seven patients had local vascular problems after the procedure. In two patients, there was persistence of hypertension necessitating drug therapy. On haemodynamic and angiographic restudy in 10 patients, one patient had restenosis and none had aneurysm formation. We conclude that balloon angioplasty is a safe, and less invasive alternative to surgery for native aortic coarctation with gratifying immediate and short term results. PMID- 1289214 TI - Sizing of balloons in balloon mitral valvotomy. AB - In twenty six consecutive patients who underwent balloon mitral valvotomy (BMV) by the transseptal double balloon technique, the mitral valve area (MVA) increased from 0.78 +/- 0.1 cm2 to 1.80 +/- 0.3 cm2, (p < 0.001). Effective balloon dilating area (EBDA) of each combination of balloons used was calculated using a standard formula. Patients were classified into 4 subgroups with approximate EBDAs of 3.3, 4.0, 4.9 and 5.7 cm2 and they had mean post-BMV MVAs of 1.28, 1.78, 1.89 and 1.98 cm2 respectively (ANOVA F = 3.32, p < 0.05). Patients were reclassified after normalisation of EBDA and post-BMV MVA to square metre of body surface area. Three subgroups with mean normalised EBDAs of 2.32, 2.96 and 3.62 cm2/m2 had mean normalised post-BMV MVAs of 0.99, 1.17 and 1.40 cm2/m2 respectively (ANOVA F = 6.85, p 0.01). A trend towards increasing mitral regurgitation with increasing balloon size was noted. Three cases of mitral regurgitation including one case of severe mitral regurgitation occurred in the subgroup of 9 patients with largest normalised EBDAs. The overall correlation between normalised EBDAs and normalised post BMV MVA was strong r = 0.67, p < 0.01). The optimal normalised EBDA for Indian patients undergoing BMV is around 3.6 cm2/m2. Balloons used should be sized accordingly. PMID- 1289216 TI - Relation between major indices of prognosis in patients with chronic congestive heart failure: studies of maximal exercise oxygen consumption, neurohormones and ventricular function. AB - Peak exercise capacity (Peak VO2), neurohormonal changes, ventricular enlargement and ejection fraction are among the most important determinants of prognosis in congestive heart failure. However, the inter-relation between these parameters is unknown. We, therefore, correlated these indices in patients with hemodynamically severe congestive heart failure (NYHA class II, pulmonary artery wedge pressure 25 +/- 2 mm Hg, cardiac index 2.5 +/- 0.2 l/min/m2, ejection fraction 43 +/- 2% and fractional shortening 19 +/- 1%). Peak VO2 measured directly during exercise by breath to breath expiratory gas analysis using a metabolic cart was 23 ml/min/kg. Plasma epinephrine (E) and norepinephrine (NE) were measured by high performance liquid chromatography (HPLC) and plasma renin activity (PRA), aldosterone (Aldo), cortisol, prolactin, growth hormone, anti-diuretic hormone (ADH) and antinatriuretic peptide (ANP) by radioimmunoassay. Ejection fraction was measured by echocardiography. There was no relation between peak VO2 and any of the neurohormones E: r = -0.43, NE: r = -0.43, ANP: r = -0.49, Cortisol: r = 0.37, ADH: r = -0.07, Aldo: r = -0.45, 2 tail critical value 0.55. PRA showed a modest correlation (r = -0.61). Similarly, there was no relation between ejection fraction or degree of ventricular enlargement and any of the other indices (r = 0.05). We conclude that although peak VO2, neurohormonal profile and ventricular function are important individual prognostic determinants, there seems to be no direct relation between them. PMID- 1289217 TI - Long term follow up study of prognostic significance of exercise duration during treadmill stress test in patients with stable coronary heart disease. AB - Treadmill stress tests provide useful noninvasive prognostic information in patients with coronary heart disease (CHD). The present study has prospectively analysed the long term prognostic value of exercise tolerance as measured by exercise time during treadmill stress test in 335 consecutive patients with stable CHD. 161 had exercise time of 6 minutes or less (mean 4.58 +/- 1.54 minutes) on a modified protocol (Group A) and 174 had exercise time of more than 6 minutes (mean 9.30 +/- 0.74 minutes)(Group B). Both groups were matched for major coronary risk factors (hypertension, smoking, diabetes and cholesterol levels) and type of drug therapy (betablockers, nifedipine, diuretics and aspirin). The patients have been followed up for upto 9 years with a mean of 6.28 +/- 2.99 years (Group A) and 7.87 +/- 1.98 years (Group B). Actuarial analysis shows that the overall survival after dropout due to death or coronary artery bypass surgery was significantly lower in group A [dropouts = 66 (41.0%)] than in Group B [dropouts = 19 (10.9%)] (Logrank test = 39.94, p < 0.001). The mortality was significantly higher in Group A with 58 deaths (36.0%) as compared to Group B with 16 deaths (9.2%) (x2 = 34.98, p < 0.001). The crude death rate was 5.73% per year in Group A as compared to 1.17% per year in Group B. The incidence of sudden deaths was also higher in Group A with 28(17.4%) instances as compared to 5(2.9%) in Group B (x2 = 19.85, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289218 TI - Association between incidence of lipoprotein(a) positivity and coronary heart disease. AB - Serum samples from 167 (109 male, 58 female) hospital based staff as controls and 760 (596 male and 164 female) clinically documented patients of coronary heart disease (CHD) were subjected to 3.75% polyacrylamide gel electrophoresis for lipoprotein profile and the presence of lipoprotein(a) [LP(a)], which is reported to be an independent risk factor for CHD. Serum total cholesterol, triglyceride and ratio of the electrophoretically separated LDL/HDL lipoprotein fractions were also evaluated. The significant observations are (i) a large proportion of both male and female CHD patients showed the presence of LP(a) as compared to controls, (ii) The incidence of LP(a) positivity was found to be independent of sex and age in controls. Female patients however showed marginal increase (p < 0.05) with age. Male patients of < 40 years demonstrated three times higher incidence of LP(a) presence as compared to their female counterparts, (iii) Comparison of LP(a)+ and LP(a)- patients for serum lipid levels did not show any significant difference. It is inferred that LP(a) positivity may be independent of these lipid variables. PMID- 1289219 TI - Silent myocardial ischaemia and cardiac autonomic neuropathy in diabetics. AB - Treadmill exercise electrocardiography was performed in 47 patients of diabetes to detect latent coronary artery disease. Eighteen patients (36.3%) were found positive on treadmill test. All forty seven subjects were evaluated for cardiac autonomic neuropathy. The incidence of cardiac autonomic neuropathy in treadmill positive group was 72.2% as compared to 31.0% in treadmill negative group, (p < 0.01). Nine patients from the positive group and 4 patients from the negative group were subjected for coronary angiography, which revealed significant CAD in 8 and 1 subjects in both groups respectively. It is concluded that the incidence of silent myocardial ischaemia in diabetics is very high and cardiac autonomic neuropathy seems to be the most probable reason for absence of pain. PMID- 1289220 TI - Haemodynamic advantage with single chamber rate responsive pacemakers over dual chamber pacemakers during exercise in chronotropic incompetence. AB - Sequential cardiac chamber activation and chronotropic response are amongst the important determinants of cardiac performance. This study compared VVIR mode with DDD and VVI mode to assess the contribution of these two factors in the determination of cardiac performance during exercise. Ten patients with a mean age of 68 +/- 5 years were studied during 1988-90, who had complete heart block and sinus node dysfunction with a mean LV ejection fraction of 51.5 +/- 6.25%. Five patients had DDD pacemakers and the rest had VVIR pacemakers. Patients were exercised first in VVI mode followed by either DDD or VVIR mode. Exercise duration, maximum rate pressure product, exercise capacity and cardiac output were measured with graded treadmill test in Bruce protocol. There was remarkable increase in the exercise duration (P < 0.001) and the maximum rate pressure product (P < 0.001) in patients with VVIR as compared to DDD and VVI mode. In DDD mode, as compared to VVI mode, this increase was less remarkable, though statistically significant (P < 0.005). Therefore, it is concluded that patients with chronotropic incompetence as well as complete heart block do better during dynamic exercise when they have VVIR mode compared to VVI or DDD mode. PMID- 1289221 TI - Effects of peroxidized oil on the development of experimental atherosclerosis in rabbits. AB - Ingestion of peroxidized oil under hypercholesterolemic dietary conditions resulted in a number of biochemical and pathological changes in rabbits. Total lipids, cholesterol and glyceride levels of plasma, liver and aorta were significantly higher in peroxidized oil fed rabbits, compared to the ones receiving normal oil. The degree of atherosclerosis and the severity of histopathological changes were significantly higher in rabbits fed with peroxidized oil. PMID- 1289222 TI - Pulmonary embolisation of right sided intracardiac masses--report of two cases. PMID- 1289223 TI - Rheumatic heart disease: a school survey in a rural area of Rajasthan. AB - Thirty four of 10168 school going children were found to have rheumatic heart disease (RHD) in a school survey conducted in the rural areas of Churu district in Rajasthan. The prevalence rate was 3.34/1000. A high prevalence of RHD was found in 11 to 15 year age group. Maximum prevalence of RHD was in low socioeconomic group. Out of these thirty four cases of RHD, isolated mitral stenosis was present in sixteen, isolated mitral regurgitation in four, combined mitral stenosis and mitral regurgitation in ten patients. PMID- 1289224 TI - Atrio-pulmonary connection (modified Fontan) for double outlet right ventricle with superior inferior ventricles and criss cross circulation. PMID- 1289225 TI - Percutaneous removal of a non radio-opaque venus sheath from the common iliac vein using a Dormia basket. PMID- 1289226 TI - Genetic variants of serum albumin: a study of albumin Kashmir. AB - The study of human serum albumin variants is reviewed with reference to albumin Kashmir, a typical variant. Its published instances are listed and its position in this field of investigations is indicated. PMID- 1289227 TI - Legume lectins: homologous proteins with similar structure but distinct carbohydrate binding specificity. PMID- 1289228 TI - A 500 MHz proton NMR study of interaction of tripeptides Lys-Tyr-Lys and Lys-Phe Lys with deoxydinucleotide d-CpG. AB - The binding of di- and tetranucleotides with tri- and tetrapeptides containing Tyr, Trp, Phe having lysine on both ends has been studied using a 500 MHz proton NMR. The results show that d-CpG exists as a right-handed B-DNA structure with both sugars in 01'-endo sugar conformation and glycosidic bond angle as in anti domain. On binding to tripeptide Lys-Tyr-Lys, the Tyr ring protons shift upfield by 0.015 ppm at 285 degrees K, while the conformation of d-CpG remains unchanged. Change in chemical shift of Tyr and nucleotide protons decreases with temperature. This upfield shift is attributed to stacking with bases/base-pairs. The presence of intermolecular NOE's also supports this. Results of binding of d CpG to Lys-Phe-Lys are similar to those with Lys-Tyr-Lys except that the chemical shift changes occur to a lesser extent. On comparing the results obtained with three different peptides, it is found that interaction decreases in the order Trp > Tyr > Phe which is similar to that found by theoretical energy calculations (reported elsewhere) and fluorescence measurements. The results also exhibit a specificity in recognition of these amino acid residues by dinucleotides. PMID- 1289229 TI - Crystal structure of cadaverine dihydrochloride monohydrate. AB - The structure of cadaverine dihydrochloride monohydrate has been determined by X ray crystallography with the following features: NH3+ (CH2)5NH3+.2Cl-.H2O, formula weight 191.1, monoclinic, P2, a = 11.814(2)A, b = 4.517(2)A, c = 20.370(3)A, beta = 106.56 degrees (1): V = 1041.9(2)A3; lambda = 1.541A; mu = 53.41; T = 296 degrees; Z = 4, Dx = 1.218 g.cm-3, R = 0.101 for 1383 observed reflections. The crystal is highly pseudo-symmetric with 2 molecules of cadaverine, 4 chloride ions and 2 partially disordered water molecules present in the asymmetric unit. Though both the cadaverine molecules in the asymmetric unit have an all trans conformation, the carbon backbones are slightly bent. Between the concave surfaces of two bent cadaverine molecules exists water channels all along the short b axis. The water molecules present in the channels are partially disordered. PMID- 1289230 TI - Spectrophotometric study of the relative affinities of teichoic acid for different metal ions. AB - Spectrophotometric study of the relative affinities of teichoic acid (TA) for Na+, Ca2+, Mg2+, Cd2+, Hg2+, Cu2+ and Pb2+ described on the basis of the disruption of metachromasia of dye 1,9-dimethyl methylene blue (DMMB)-polyanion (TA) system has revealed the following sequence of relative affinities of TA for these metals: Na+ < Ca2+ < or = Mg2+ < Cd2+ < Hg2+ < Cu2+ < Pb2+. Some of the metal ions particularly Pb2+ and Hg2+ have specific interactions with the dye, and induce distinct metachromatic band of the dye even in the absence of the polyanion. PMID- 1289231 TI - Studies on induction of metachromasy in cationic dye pinacyanol chloride by Klebsiella K7 capsular polysaccharide. AB - The acidic capsular polysaccharide isolated from Klebsiella K7 induced metachromasy in the cationic dye pinacyanol chloride indicating its chromotropic character. Interaction of the biopolymer with the cationic dye was studied by visible absorption spectrophotometry, and thermodynamic parameters of the interaction evaluated. The polymer induced a metachromatic blue shift in the spectrum from 600 nm to 495 nm. The spectral changes were studied during interaction of the dye with the polymer at different polymer/dye molar ratios (P/D = 0 approximately 50). Effects of co-solvents on the stability of the dye polymer compound were studied. A complete reversal of metachromasy was observed upon addition of different alcohols and urea solution. Thermodynamic parameters obtained from the spectral data indicated chromotropic character of the polymer in interacting with the cationic dye molecules in solution. PMID- 1289233 TI - Identification of a non-microsomal cinnamic acid 4-hydroxylase from potato tuber (S. tuberosum) and its partial purification. AB - The cytoplasmic localisation of cinnamic acid 4-hydroxylase (CA4H) has been shown by isolation and subcellular fractionation of the enzyme in Hepes buffer. The enzyme was purified by ammonium sulphate fractionation followed by AcA-34 molecular sieve chromatography. The enzyme existed as a high molecular mass which dissociated to a lower form on dilution on the column. The pH optimum, sulphydryl requirement, molecular and preliminary kinetic characteristics were investigated. PMID- 1289232 TI - Effect of nitrous oxide and methionine on hepatic S-adenosylmethionine levels and in vivo histidine oxidation in rats. AB - Nitrous oxide (N2O) decreased in vivo oxidation of histidine in rats fed a basal diet marginally deficient in methionine, although hepatic levels of S adenosylmethionine (AdoMet) were not significantly altered. Excess dietary methionine increased hepatic levels of AdoMet and increased histidine oxidation. However, it did not protect histidine oxidation when the rats were treated with N2O. Parenteral administration of methionine greatly increased hepatic levels of AdoMet and increased histidine oxidation in normal and N2O treated rats. This indicates that when hepatic levels of AdoMet are greatly elevated by administration of methionine, N2O does not affect in vivo histidine oxidation. PMID- 1289234 TI - Effect of picroliv on low density lipoprotein receptor binding of rat hepatocytes in hepatic damage induced by paracetamol. AB - Picroliv from root and rhizome of Picrorhiza kurroa showed reversal of low density lipoprotein (LDL) binding to paracetamol-induced damaged hepatocytes of rats. Changes in levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, conjugated dienes and lipids of hepatocytes were significantly prevented by picroliv at different doses. The effect of picroliv on enzyme levels, LDL receptor binding and lipids in damaged hepatocytes was found to be comparable to silymarin, a known hepatoprotective agent. PMID- 1289235 TI - Interaction of pulmonary surfactant-associated protein (SP-A) with surfactant lipids. AB - A pulmonary surfactant-associated protein complex with components of 36, 32 and 28 kDa was isolated from human lung homogenates and reassembled with surfactant lipids prepared as small unilamellar liposomes. The role of divalent cations in the assembly of this recombinant lipoprotein complex was studied by monitoring the changes in turbidity, intrinsic tryptophanyl fluorescence and surface activity. The protein-facilitated lipid aggregation was promoted on addition of 5 to 20 mM Ca2+. Intrinsic fluorescence measurements on SP-A (28-36 kDa) indicated that the tryptophan side chains were in a relatively hydrophobic environment, that the wavelength of maximum fluorescence emission and also the relative fluorescence, were changed upon the binding of lipid. Tryptophanyl fluorescence of the lipoprotein assembly was quenched as indicated by a reduction in the effective Stern-Volmer constant. These results suggest that Ca2+ lipid-protein interactions are involved in the structure and function of extracellular lung surfactant assembly. PMID- 1289236 TI - Synthesis and secretion of VLDL by rat hepatocytes--modulation by cholesterol and phospholipids. AB - The synthesis and secretion of apoB, the major protein component of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), were studied using rat hepatocytes maintained in primary culture. Supplementation of hepatocytes with rat serum VLDL and LDL increased the production of apoB while delipidated lipoproteins had no significant effect, suggesting a role for lipids in the production of apoB. Addition of cholesterol to the culture medium also increased the production of apoB in a concentration-dependent manner. Pulse labelling followed by chase in presence of cholesterol indicated enhancement in apoB secretion. Mevinolin which inhibits cholesterol synthesis significantly reduced the secretion of apoB. The presence of phosphatidylcholine and phosphatidylethanolamine in the culture medium also increased the secretion of apoB into the medium. These data suggest that availability of lipids, particularly cholesterol, is an important determinant of apoB synthesis and secretion as VLDL. PMID- 1289237 TI - Bordetella pertussis extract induces increase in the activities of glycolytic enzymes in mouse liver. AB - The hypoglycemic effect of Bordetella pertussis (Challenge strain No.18323) purified cell extract (protein with traces of carbohydrates, 2 mg%) administered (0.1 mg/100 g body wt. i.v.) into mice on the activities of the key regulatory enzymes, viz. glucokinase, phosphofructokinase, pyruvate kinase, glyceraldehyde phosphodehydrogenase, glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase, of glycolytic pathway in liver has been studied at varying intervals after injection. The maximum hypoglycaemic effect was observed at the end of 12 hr, while activities of all the enzymes studied showed significant enhancement after 18 hr, thus suggesting increased glucose utilization towards the formation of pyruvate. Actinomycin D is found to inhibit stimulation of G-6 PD activity in B. pertussis treated animals, thereby indicating the role of B. pertussis in synthesis of this enzyme. PMID- 1289238 TI - Value issues in biomedical science: public concerns and professional complacency. AB - Biomedical research was once an unquestioned good, and generous funding for a short time allowed researchers to work on whatever interested them. Two contradictory pressures have changed this. As costs have risen and economic rationalism has become politically dominant, governments, private corporations and granting agencies have increasingly demanded compliance with their own priorities, instrumental values and performance criteria. On the other hand, social and ethical critics have characterized biomedical research as being out of touch with real health needs and community values and as being an agent of social control that entrenches the power of a technocratic hegemony. The profession has largely acquiesced in bureaucratic and corporate intervention in exchange for continued funding, and assumed that social concerns could be allayed by 'top down' paternalistic education of the public. However, this response tends to add weight to the criticism that biomedicine is an agent of social control. What is needed is a spirited defence of the value of independent scholarship and research that is not limited to science but includes the humanities. Equally important is a process of community education in which scientists not only transmit their knowledge and enthusiasm to the public, but themselves become open to the social and ethical concerns of the community. PMID- 1289239 TI - Inhibition of adjuvant arthritis in the rat by phosphosugars and the alpha glucosidase inhibitor castanospermine. AB - The development of joint inflammation of adoptively transferred arthritis in rats was inhibited by treatment with the simple sugar mannose-6-phosphate or the alkaloid inhibitor of alpha-glucosidase, castanospermine. Mannose-6-phosphate was effective at a dose of 25 mg/kg per day delivered via mini-osmotic pumps implanted either subcutaneously or intraperitoneally. Castanospermine was given orally in the drinking water and rats ingested on average 60-65 mg/kg per day. Histological examination of tissue from treated rats revealed greatly reduced inflammatory infiltrates into the synovium and surrounding tissue. Castanospermine not only inhibited the development of arthritis but also inhibited the progression of the disease when treatment was commenced after the onset of symptoms. Possible mechanism(s) of action of these compounds could be their ability to inhibit the passage of leucocytes through vascular subendothelial basement membranes by inhibiting the function or expression of leucocyte cell surface-bound enzymes that are essential for such migration. Castanospermine could also inhibit inflammation through its ability to prevent the expression of adhesion molecules, which may be necessary for the capture and retention of leucocytes in the inflamed tissue. PMID- 1289240 TI - Serological responses and immunity produced in salmonids by vaccination with Australian strains of Vibrio anguillarum. AB - The Australian populations of rainbow trout (Onchorhynchus mykiss) and Atlantic salmon (Salmo salar) were found to have similar immunological responses to local strains of Vibrio anguillarum as those reported for the more genetically diverse populations of these fish and strains of V. anguillarum found in the Northern Hemisphere. In addition, our studies more precisely defined the respective responses of rainbow trout and Atlantic salmon to immersion vaccination by the bath and dip methods. PMID- 1289241 TI - What is the selective pressure that maintains the gene loci encoding the antigen receptors of T and B cells? A hypothesis. AB - The dominant view is that the gene loci encoding the B cell antigen receptor (BAr) or the T cell antigen receptor (TAr) specify a vast array of combining sites. The 'germline' repertoire is estimated to be > 10(10) by multiplying numbers of subunit complements by DN-region variability. This implies that the germline can be maintained by a selection imposed by all or most of the antigenic universe. Its unchallenged popularity, notwithstanding, this neo-germline view is untenable and hence the need for a competing concept, as presented here. The immunoglobulin (Ig) loci are under a totally different selection from the T loci. The Ig loci are selected upon largely by carbohydrate determinants on pathogens that vary more slowly than the proteins produced by the Ig loci, which are necessary to rid these selective antigens. By contrast, the T loci are selected to recognize the allele-specific determinants on restricting elements encoded in the major histocompatibility complex (MHC). The expression of the germline results in a high copy number (HCN) repertoire; this repertoire is the substrate for 'mutation' that yields the low copy number (LCN) repertoire. For the B cell, these two repertoires interact to optimize the response to the unexpected. For the T cell, only the LCN repertoire is functional. The immunoglobulin (Ig) loci are selected upon as light(L)-heavy (H) pairs; the T loci are selected upon as single units alpha or beta (i.e. the VT-gene segments act as a single pool). This competing concept carries with it many important and testable consequences. PMID- 1289242 TI - The importance of T cell homing and the spleen in reaching a balance between malaria immunity and immunopathology: the moulding of immunity by early exposure to cross-reactive organisms. AB - It takes a number of years to develop clinical immunity to malaria and malaria pathology is also most evident a number of years after birth. T cells are known to play an important role in defence from malaria parasites but may also contribute to the disease symptoms associated with malaria. T cells which react against malaria parasites have arisen through stimulation with organisms which cross-react with malaria or through exposure to the malaria parasites themselves and express a memory phenotype (CD45Ro+, CD45Ra-, CD4+). T clones which have arisen through exposure to cross-reactive organisms may be expected to home to the tissues where initial exposure occurred as determined by tissue-specific adhesion molecules on the lymphocyte surface. Such tissues may not be appropriate to parasite killing and localization of T cells in such sites may contribute to the immunopathology of malaria. The sharp increase in immunity and decline in pathology observed in later childhood in malaria endemic areas may result from an increase in the number of T cells induced by the parasite itself (as opposed to cross-reactive organisms). Such T cells may not have a preferential trafficking to other organs and may be more likely to circulate through the spleen. Splenic changes may also allow more malaria-specific T cells to concentrate in the spleen and may facilitate interactions between T cells, monocytes, neutrophils and parasites resulting in parasite death. Whereas cytokines secreted by parasite reactive T cells in all locations may contribute to cerebral malaria and other forms of pathology, cytokines in the spleen at least, should directly contribute to parasite death. PMID- 1289243 TI - Development of human ABO blood group A antigen on Escherichia coli Y1089 and Y1090. AB - Studies by other workers have shown that some strains of Escherichia coli have surface antigens analogous to the human blood group ABH antigens, and that these are carbohydrates associated with membrane lipopolysaccharides. This study has demonstrated that E. coli strains Y1089 and Y1090 possess the H antigen, which can be converted to the A antigen by incubation with A-transferase (N-acetyl galactosaminyl transferase) and A-sugar (UDP-N-acetyl-galactosamine). Such cells will then form mixed agglutinates with human A red cells and human polyclonal (but not mouse monoclonal) anti-A antibodies. E. coli Y1089 and Y1090 have endogenous enzymes that use the A-sugar (in the absence of A-transferase) to produce a variant A antigen. Cells expressing this variant antigen adsorb anti-A antibodies but do not participate in mixed agglutination with human group A red cells. It is estimated that E. coli Y1089 and Y1090 possess approximately 5000 H epitopes per cell that can be converted to A epitopes. PMID- 1289244 TI - Macrophages in protective immunity to Hymenolepis nana in mice. AB - When mice were treated with carrageenan just before infection with eggs of Hymenolepis nana, they failed to exhibit sterile immunity to the egg challenge, with evidence of a decrease in the number of peripheral macrophages (Mo) and the rate of carbon clearance. Although there were high levels of interleukin-1 (IL-1) released into the intestinal tracts of the parasitized mice at challenge infection, there was almost no release of IL-1 in those treated with carrageenan just before challenge. These results strongly suggest that Mo have an important role in protective immunity to H. nana in mice. PMID- 1289245 TI - Effect of alcohol on serum lipids & lipoproteins in male drinkers. AB - The evaluation of the effect of moderate and high doses of ethanol on the serum levels of triglyceride (TG), total cholesterol (TC), cholesterol content of very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), HDL2, HDL3 subfractions and apoproteins: apo-AI and apo-B was undertaken in 45 (25 controls, 10 moderate and 10 high dose drinkers) healthy males. The results of this preliminary study showed a significant rise in total HDL-cholesterol and apo-AI levels of alcoholics of both the groups. Out of the two subfractions, HDL2 appeared to be induced more. Increased levels of atherogenic lipids (TG, VLDL-chol., LDL-chol. and apo-B) were found in high as well as moderate drinkers. Our results suggest that the benefit of alcohol intake need to be weighed carefully against its considerable risks. PMID- 1289246 TI - An interactive image analysis system for quantitative cytology & to classify cervical cells. AB - Introduction of computers and image analysis systems are gaining faster momentum in order to quantitate the assessment of cells for diagnosis and prognosis, and this system aims to relieve the operator from the tedium of microscopic observation and reduce operator bias and human error. This paper discusses the design and configuration of an interactive image analysis system built in the laboratory for the purpose of cell analysis and classification. The software developed to compute various textural and morphological parameters of cells on smear are briefly described. The results of the experiments carried out to classify normal and abnormal cells on cervical smear show 94 per cent success rate. PMID- 1289247 TI - An immunoradiometric assay for measurement of serum thyroglobulin. AB - A two-site immunoradiometric assay (IRMA) for estimation of serum thyroglobulin (tg) is optimized using partially purified rabbit anti-tg antibodies (ammonium sulphate precipitated) as a solid phase antibody and affinity purified 125I labeled anti-tg antibodies as a tracer. The IRMA correlated well (r = 0.93, n = 200, P < 0.001) with conventional radioimmunoassay (RIA). The inter- and intra assay coefficient of variation were comparable for both methods. The IRMA method gave a superior sensitivity and working range (2 ng/ml, 3-1000 ng/ml) as compared to that of RIA method (6 ng/ml, 9-500 ng/ml). Using IRMA the total incubation time was curtailed to 4 h as compared to 90 h required for conventional RIA. The shelf-life of tracer antibody used in IRMA was much longer (3 months) as compared to tracer tg (3-4 wk) used in RIA. The optimized IRMA for quantitation of serum tg has superior assay characteristics as compared to RIA. PMID- 1289248 TI - Volume of semen as a parameter of its quality. AB - A total of 1655 semen samples obtained from men who underwent initial semen analysis before enrolling for IVF-ET programme were analysed. The semen samples were categorized arbitrarily on the basis of volume as high (> 4.5 ml), normal (1.5-4.5 ml) and low (< 1.5 ml). The semen parameters studied vis-a-vis volume of the sample were viscosity, osmolality, motility, sperm count and morphology. The different volume groups were also compared to the overall quality of the sample. The study showed that high and low volume semen were associated with high incidence of spermatozoa exhibiting subfertile characteristics. Normal volume per se did not indicate the quality of the sample, however high and low volumes were indicators of semen of subfertile quality. There was an inverse correlation between osmolality and volume of semen sample. Thus the parameter 'volume' gives a rough estimate of the quality of the sample. PMID- 1289249 TI - Cytogenetic investigations in Down syndrome patients & their parents. AB - A total of 1343 mentally retarded patients referred for cytogenetic evaluation were studied. Of these Down syndrome was confirmed in 365 (21.17%). There were 316 patients of trisomy 21 (86.58%); 21 of mosaicism (5.75%) and 28 of translocation (7.67%). Trisomy 21 patients with chromosomal variants were observed in 17 (4.65%). A 1.37:1 male:female ratio was seen. Karyotyping was also done on 182 parents (of patients of mosaic Down, translocation Down and trisomy 21 with chromosomal variants and in parents with suspected low mosaicism). Mosaic trisomy 21 cell line was found in one mother (0.27%); 6 parents (1.65%) were seen to be translocation carriers and 7 had chromosomal variants (1.92%). Cytogenetic investigations help to give appropriate genetic counselling to patients and their families. PMID- 1289250 TI - Serum leucine amino peptidase levels as a marker in testicular tumours. AB - Serum levels of leucine aminopeptidase (LAP) were studied in 60 patients with testicular tumours and 26 normal individuals, and were found to be significantly elevated in patients with seminomas, nonseminomas and benign tumours of the testis. After treatment the LAP levels decreased in patients with seminomas, nonseminomas and mixed cell carcinomas indicating response to therapy. The quantitative method used for estimation of LAP, which is simple, quick, accurate and cost-effective, could be used more effectively as a tumour marker in testicular malignancies. PMID- 1289251 TI - Testicular biopsy in male infertility. AB - A total of 134 testicular biopsies from infertile men were studied. The potentially treatable causes of infertility viz. Normal spermatogenesis with post testicular obstruction, maturation arrest and hypospermatogenesis together constituted about 54 percent of all cases. The incurable causes viz., germ cell aplasia, tubular fibrosis and Klinefelter's syndrome together constituted about 42 percent of all cases. Testicular biopsy in male infertility is a very useful procedure since it gives a lot of information on the diagnosis and helps in planning treatment. PMID- 1289252 TI - Sequential MTX-5 FU chemotherapy in pallination of advanced cancer cervix. AB - Twenty four patients with advanced cancer of cervix were submitted to sequential chemotherapy 5FU and MTX. The response rate was 85% in stage III and 50% in stage IV. Overall response rate was 75%. Patients who had not received radiotherapy earlier responded better than those who had received it earlier. This easy and economical modality has importance in view of late reporting and advanced stage of disease encountered in our set up. PMID- 1289253 TI - Malaria--general management as recommended by WHO. PMID- 1289254 TI - Use of bovine osteogenic protein to promote rapid osseointegration of endosseous dental implants. AB - An enriched bovine osteogenic protein preparation in combination with bone collagen matrix (osteogenic protein device) was used to effect new bone growth in extraction sites in the presence or absence of titanium dental implants. Incisor and canine teeth were extracted from each of three cynomolgus monkeys, and implants were inserted directly into the sockets without surgical site preparation. The osteogenic protein device induced new bone formation in close apposition to the titanium implants in all trials within 3 weeks. A lesser amount of new bone formation in both sets of control sites was limited to the bony socket walls and not closely apposed to the implant. These data show that the osteogenic protein device is capable of inducing new bone formation in tooth sockets within 3 weeks in the presence or absence of titanium implants. This is the first known demonstration of the therapeutic induction of bone formation in close apposition to metallic implants. PMID- 1289255 TI - Optimization of surface micromorphology for enhanced osteoblast responses in vitro. AB - In vitro cellular responses of osteoblast-like cells were studied on titanium surfaces with different surface morphologies. Surface profilometry was used to determine whether rough or smooth surfaces with regular or irregular morphologies can be produced by conventional fabrication techniques. Significantly higher levels of cellular attachment were found using rough, sandblasted surfaces with irregular morphologies. These results correlate with recent in vivo findings and suggest that implants should be prepared with roughened surfaces at bony contact areas. PMID- 1289256 TI - Prosthesis design for osseointegrated implants in the edentulous maxilla. AB - The position of osseointegrated implants in the edentulous maxilla is dictated by available bone and can vary widely among patients. Anatomy limits the amount of bone available for placement of osseointegrated implants. With increasing resorption, the number, length, and position of implants are further compromised. Bone grafts are frequently needed to place implants of adequate length. The variability of implant placement indicates the need for multiple prosthesis designs in the maxilla. Prosthesis design considerations are suggested for patients with minimal, moderate, and severe resorption of the edentulous maxilla. PMID- 1289257 TI - A 3-year clinical study of Astra dental implants in the treatment of edentulous mandibles. AB - A prospective study for the treatment of mandibular edentulism using the new Astra dental implant system was conducted on 54 patients. The clinical performance of 310 implants was monitored over 3 years. The survival rate was 100% for the prostheses and 98.1% for individual implants. Four implants failed during the first 3 months after placement, one was retained as a "sleeper," and two more were removed because of persistent discomfort. Both resorption and deposition of mandibular marginal bone were observed. Bone changes from baseline to the end of the first year ranged from -0.4 to +1.0 mm (median 0.00), from the first to the third year from -0.8 to +0.6 mm (median 0.04), and over the 3 years ranged from -1.1 to +1.0 mm (median 0.01). No marked mean bone resorption was observed during the first year compared to the two following years. A significant gain in marginal bone level was recorded in males, but in females the level was unchanged. There were no serious inflammatory reactions in the surrounding soft tissues during the 3-year follow-up period. PMID- 1289258 TI - Plaque-induced inflammation around implants. AB - This article is a review of plaque-induced inflammation around dental implants. The microflora around successful implants is similar to healthy sulci, while that associated with failing implants is similar to periodontally diseased sites. Implant microflora is similar to the tooth microflora in the partially edentulous mouth. The microflora of implants in partially edentulous mouths differs from that in edentulous mouths. This seems to indicate a bacterial reservoir around the teeth and the possibility of reinfection of the implant sulcus by periodontal pathogens. The maintenance of a tooth microflora consistent with periodontal health in partially edentulous mouths may lead to maintaining an implant microflora consistent with peri-implant health. Thus, periodontal and implant maintenance are linked and neither can be overlooked. PMID- 1289259 TI - Reduced corrosion of CP Ti and Ti-6A1-4V alloy endosseous dental implants after glow-discharge treatment: a preliminary report. AB - Inductively coupled argon plasma spectroscopic analysis was used to quantify titanium, aluminum, and vanadium corrosion products released by superficial layers of identically shaped commercially pure titanium and Ti-6A1-4V alloy dental implants. Halves of each of two originally sterile groups were analyzed directly from the manufacturer's packaging and the other halves received glow discharge treatment prior to their corrosion assay. The implants were incubated in pH 3 modified saline solution and were analyzed after 2- and 12-week corrosion periods. Implants treated with glow discharge showed statistically significant reduction in the amounts of corrosion products released, apparently as a result of glow-discharge-produced surface oxides of greater passivity than originally present. PMID- 1289260 TI - The influence of occlusal surface material on peak masticatory forces using osseointegrated implant-supported prostheses. AB - Masticatory forces associated with porcelain and acrylic resin occlusal surfaces on osseointegrated implant-supported prostheses opposing natural teeth were studied in five healthy subjects. A three-channel electronic force transducer carrying a fixed prosthesis with either acrylic resin or porcelain occlusal surfaces and balanced articulation was used to record masticatory forces while the subjects chewed various foods. It was found that mean peak masticatory forces varied considerably from subject to subject but were consistent within each subject. No differences related to tooth material could be detected in the load rates. Forces directed away from the implants were noted in all subjects. PMID- 1289261 TI - Loads and designs of screw joints for single crowns supported by osseointegrated implants. AB - The problem of screw stability was approached in this study by calculating the maximum occlusal forces in vivo for patients with single implant restorations (which use only one screw to secure the prosthetic reconstruction to the implant). The measurements of occlusal forces together with geometric parameters for the individual patients were used to determine the necessary holding capabilities of the screw joint. Different screw designs were tried in bench test situations and the results were compared with clinical situations. A gold alloy screw with a flat head and high tightening torque (35 Ncm) produced the best results. PMID- 1289262 TI - Reconstruction of maxillary alveolar defects with mandibular symphysis grafts for dental implants: a preliminary procedural report. AB - Partially edentulous patients with alveolar defects contraindicating implant placement were treated with bone grafts obtained from the mandibular symphysis. Complications encountered were minor and uneventful. Evaluation 4 months after surgery revealed minimal graft resorption, thus implant placement was possible in all potential sites. Advantages of the symphysis graft include easy access, availability of greater quantities of bone over other intraoral donor sites, low morbidity, no hospitalization, minimal discomfort, no alteration in ambulation, and no cutaneous scar. Compared with other bone regenerative methods for implant placement, a superior quality of bone was found and a shorter healing period is required. Results of this preliminary clinical investigation demonstrate that chin grafts offer a viable alternative for reconstruction of alveolar defects prior to dental implant placement. PMID- 1289263 TI - Risk factors associated with dental implants in healthy and medically compromised patients. AB - A total of 104 consecutive patients treated with 313 Nobelpharma implants was studied to determine the medical risks associated with dental implants. There did not appear to be an increased implant failure rate or an increase in perioperative morbidity in patients with a compromised medical status. Age; sex; and concurrent use of hypoglycemic agents, supplemental female hormones, or steroids also did not correlate with increased implant failure or perioperative morbidity. Implant procedures using a variety of pain-/anxiety-control agents failed to reveal any increase in anesthetic-related complications. However, the number of implants placed per patient did correlate with implant failure. It appears that implant surgery and the required anesthetic appear to be safe procedures even in the medically compromised patient. PMID- 1289264 TI - The role of computerized tomography in dental implantology. AB - Dental implant therapy has dramatically expanded the treatment options available for both the partially and completely edentulous patient. Advances in the use of dental implants have necessitated the inclusion of additional diagnostic procedures in the treatment planning process to optimize the site and angulation of fixtures and, consequently, the success of prosthetic restorations. One of these procedures is computerized tomography. Originally introduced as a medical diagnostic technique, it has been adapted for many uses in dentistry. This article reviews the role of computerized tomography in dental implantology. Its advantages, disadvantages, and indications are presented. PMID- 1289265 TI - A utility analysis of dental implants. AB - By applying a utility (usefulness) scale termed the "Feeling Thermometer" to 111 edentulous patients, a measure of effectiveness (quality-adjusted prosthesis years) that can be compared across several treatment strategies was developed. The results suggest that the utility scale was a valid (known group, P < .05), reliable (intraclass correlation coefficient = .713) measure of patients' preferences for the three treatment strategies: (1) conventional complete dentures (controls, n = 77), (2) transosteal implant-supported prostheses (n = 19), and (3) endosseous implant-supported prostheses (n = 15). The implant treated patients rated their prostheses as high or higher (Feeling Thermometer score of 86.3 [endosseous] and 82.3 [transosteal]) than a functional fitting, esthetic conventional denture (score of 85.0 [endosseous] and 82.0 [transosteal]). They were also younger, more educated, and had received more sets of dentures (P < .05) than conventional denture patients. PMID- 1289266 TI - Isotope diagnostics, CT and MR in urinary tract diseases of infants and children. AB - Ninety-nine isotope, 4 CT and 10 MR examinations were carried out in 1990 to test urogenital disorders in infants and children. The procedures are described with sidelights on indication, difficulties of technical nature and comparison with internationally published reports. An examination strategy is devised, with estimation of its effectiveness in the follow-up and after-care. PMID- 1289267 TI - Ultrasonographic screening of neonatal adrenal apoplexy. AB - A total of 1785 newborns were subjected in the course of 14 months to ultrasonographic screening. Adrenal bleeding among those born via caesarean section has not been recorded. Among 1490 born via vagina there were 14 (0.94%) with adrenal apoplexy and 80 were delivered with clavicular fracture (5.37%). There were 13 with unilateral bleeding. Hormone examination applied to one infant with bilateral bleeding confirmed adrenal insufficiency which normalized after three months. In the aetiology of neonatal adrenal apoplexy the dominant causative role is attributed to birth trauma. PMID- 1289268 TI - Differential diagnosis of adrenal tumour and upper pole renal tumour by I-131 cholesterol adrenocortical scintigraphy. AB - A 27-year-old housewife with right hypochondralgia was admitted for treatment of a huge right adrenal or upper pole renal tumour. The tumour measured 10 x 8 x 8 cm and was hypovascular. The main blood supply derived from the right adrenal artery which originated from the abdominal aorta just proximal to the right renal artery. Although several diagnostic imaging studies suggested that the tumour arose from the right adrenal gland, the bilateral adrenal glands were equally visualized on I-131 cholesterol adrenocortical scintigraphy. After surgery and pathological examination, the tumour proved to be a renal cell cancer, while the right adrenal gland was intact. This case demonstrates that adrenocortical scintigraphy is useful in the differentiation of adrenal and renal tumours when a large tumour occupies the upper pole of the kidney or adrenal gland. PMID- 1289269 TI - Renal cell carcinoma in chronic renal failure without dialysis treatment. AB - We report a case of renal cell carcinoma in chronic renal failure without dialysis treatment. The literature is reviewed, and the relationship between renal cell carcinoma and uraemia is discussed. PMID- 1289270 TI - Urinary infection and stone formation as complications of Gil-Vernet's antireflux procedure. AB - The authors describe two cases of urinary infection and stone formation as late complications of Gil-Vernet's antireflux treatment. The immediate cause of these complications was the migration to the mucosal surface of the nonabsorbable sutures employed in this technique. PMID- 1289271 TI - Recurrence of superficial bladder tumours after transurethral resection. AB - From 1979 to January 1990, 48 patients with newly diagnosed superficial bladder tumours were treated by transurethral resection (TUR) at Toyama Medical and Pharmaceutical University Hospital. The relationship between tumour recurrence and the stage, grade, number, or size of the tumours was investigated. The 1-, 2 , 3-, 4- and 5-year non-recurrence rates were 72%, 63%, 47%, 40%, and 40%, respectively. Non-recurrence rate for pTa tumours was significantly higher than that for pT1 tumours (p < 0.05). There was no relationship between tumour grade and recurrence. The rate of recurrence of multiple tumours was higher than that of single ones. There was no difference in non-recurrence rate between tumours smaller than 1 cm and those of 1 cm or larger. Non-recurrence rate in the instillation therapy group was significantly higher than in the non-instillation group (p < 0.05). It was concluded that patients with multiple or high-stage tumours have the risk of a high rate of recurrence and that intravesical chemotherapy is effective in preventing local recurrence in some patients. PMID- 1289272 TI - The influence of bilateral orchiectomy on volume changes of the prostate in men with advanced prostatic cancer--the predictive value. AB - The changes of prostatic volume were evaluated in 84 men with adenocarcinoma of the prostate treated by bilateral orchiectomy. In every case the greatest volume decrease was observed during the first month after castration. In 56 patients (66.6%), where the response to orchiectomy was better, the reduction of prostatic volume was considerably greater and diminished more rapidly than in the remaining 28 patients (33.3%), where the reaction to the treatment was worse. PMID- 1289273 TI - Germ cell neoplasms in three intersex patients with 46,XY karyotype. AB - This report presents 3 cases with gonadoblastoma mixed with other germ cell tumours in intersex patients, all with a 46,XY karyotype. One 11-year-old patient was a true hermaphrodite, the others, aged 13 and 18, respectively, had both gonadal dysgenesis. Different clinical courses have been noted. Two patients had gonadoblastoma combined with dysgerminoma; in one of them a teratoma was also found. In the third case gonadoblastoma was transformed into teratocarcinoma. The malignant degeneration was more serious in the 2 pubertal patients. Thus, we recommend early and prophylactic gonadectomy. PMID- 1289274 TI - Primary malignant melanoma of the scrotum. AB - The authors describe a rare case of primary scrotal neoplasm. The necessity of a prompt diagnosis is emphasized. PMID- 1289275 TI - Meatal advancement and glanuloplasty: a report on 25 cases. AB - We report on 25 children who underwent repair of distal hypospadias with the meatal advancement and glanuloplasty technique. The principles of this operation were safe and there were no complications. Meatal advancement and glanuloplasty proved to be a successful and reliable procedure in the properly selected child with distal hypospadias. PMID- 1289276 TI - Ultrasonic changes in primary gouty nephropathy. AB - Investigations were carried out in a total of 60 patients with gouty nephropathy (GN), chronic glomerulonephritis (CGN) and chronic pyelonephritis (CPN), respectively. The aim of the study was to compare ultrasonic changes in the three diseases. PMID- 1289277 TI - Continuous arteriovenous haemodialysis and haemofiltration in intensive care acute renal failure patients. AB - CAVHD and CAVH were compared regarding uraemic control in 13 critically ill intensive care patients with acute renal failure (ARF). Patients' mean age was 60 years. Pretreatment blood urea range was 17-56 mmol/l (33-56 mmol/l in 70% of the patients). All patients received vasopressor drugs, and 92% were on artificial mechanical respiration. From the results of this study both modalities gave adequate uraemic control. There was a notable decrease in the urea and creatinine levels with CAVHD more than with CAVH. There was no statistically significant difference between the two modalities in the urea clearance. However, a significant difference (P < 0.05) in creatinine was obtained with CAVHD. Our results suggest that CAVHD is a useful alternative to CAVH in ARF especially when the blood urea level is > 30 mmol/l. However, a higher dialysate flow rate (e.g. 25 ml/min) should be used if the urea level is more than 40 mmol/l. CAVH should be reserved for ARF patients in whom fluid overload is a major problem. PMID- 1289278 TI - Candida peritonitis: successful treatment with CAPD in two patients. AB - The authors treated seven patients with CAPD between September 1986 and December 1990. In two of them Candida peritonitis was observed. The pathogen proved to be Candida albicans in both cases. The traditional antimycotic treatment resulted in a temporary improvement in both patients; complete healing was only achieved after removal of the Tenckhoff catheter. Subsequently both patients were put to haemodialysis. Successful renal transplantation was performed two weeks and three months, respectively, after removal of the catheter. The authors' experience supports the opinion that removal of the Tenckhoff catheter constitutes the most important move in the management of Candida peritonitis. PMID- 1289280 TI - Conversion of the arthrodesed hip to a total hip arthroplasty. Indications and limitations. AB - Arthrodesis of the hip is thought to achieve satisfactory clinical and functional results in the adult despite the loss of articular mobility involved (Santori et al., 1986; Russel, 1987; Weber, 1987). Over the long term, however, most patients develop secondary degenerative arthritis in the spine, contralateral hip, and knees due to overloading. The deteriorating condition of these joints eventually causes the onset of pain, which often requires further intervention. Surgery on these joints may yield satisfactory short-term results, but these will not last if the arthrodesed hip is not converted to total hip arthroplasty either prior to or at the same time as such operations. PMID- 1289279 TI - Effect of haemodialysate and its peptide fractions on lactate dehydrogenase activity in erythrocytes from healthy subjects and patients with end-stage renal disease. AB - The effect of haemodialysate and its 3 peptide fractions on lactate dehydrogenase activity in erythrocytes was studied in patients treated by repeated haemodialysis for end-stage renal disease and in healthy subjects. Erythrocytes from dialyzed patients showed significantly lower LDH activity than those from healthy subjects. After a 3-h incubation with haemodialysate (675 and 450 micrograms protein/ml), or its peptide fraction III (270 and 190 micrograms protein/ml), a significant inhibition of LDH activity was observed. On the other hand, neither haemodialysate nor its peptide fractions inhibited LDH activity in red blood cells from patients with end-stage renal disease treated by repeated haemodialysis. PMID- 1289281 TI - Hip deformity and dislocation in spina bifida. AB - A group of 118 patients with spina bifida treated between 1960 and 1988 was reviewed with a focus on the problem of hip deformity and dislocation. Deformity can be avoided by physical therapy and correct posture. Hip dislocation often occurs in cases of high or mid-lumbar lesions; at lower levels subluxation is more common. In choosing appropriate treatment, the most important consideration is the patient's true functional potential. If the patient is either not ambulatory or severely impaired, his or her condition will not be exacerbated by a dislocated hip. PMID- 1289282 TI - Thigh pain in cementless hip replacement. Clinical and radiographic correlations. AB - The authors analyse a series of 35 Rippen System cementless hip joint prostheses implanted in 32 patients from May 1987 to September 1988. Certain radiographic parameters were studied in an attempt to find a correlation with the clinical results. Special attention was paid to the high incidence of thigh pain, attempting to identify the cause through radiographic study of the bone-implant interface. Even when analyzed using Kappa statistics, the correlation between the clinical and radiographic findings was purely incidental. In agreement with the literature, the authors identify some elements which should be investigated further such as primary temporary fixation of the stem, reduction of micromotion, and biocompatibility of the materials. PMID- 1289283 TI - Rotator cuff tears. Results of surgical repair. AB - A prospective study was done on 73 patients who underwent surgical repair of a rotator cuff tear. The patients were divided into four groups according to the active shoulder flexion and the trophism of the rotator cuff muscles: group A- range of motion > 100 degrees; group B--ROM 60-100 degrees; group C--ROM < 60 degrees; group D--ROM < 100 degrees and significant muscle hypotrophy. The rotator cuff tears were classified into four groups at surgery according to size: grade I measured < 2 cm; grade II measured 2-4 cm, grade III measured > 4 cm but was reparable; and grade IV was irreparable. The results were evaluated after an average follow-up of 2.3 years and correlated to several factors including the preoperative clinical assessment, the size of the lesion, the type of lesion (tear or detachment), and the mechanism of injury (traumatic or atraumatic). Seventy-three percent of the cases had satisfactory results. The preoperative clinical assessment and the size of the tear were the most important indicators of the final outcome. The proportion of satisfactory results underwent a progressive decline from group A (88%) to group D (14%) and from grades I and II (88% and 89%, respectively) to grade III (56%) and grade IV (none). Rotator cuff repair is almost always successful in patients with more than 60 degrees of active arm flexion and either small or medium-size tears. Less than two-thirds of the patients with major tears and less than 60 degrees of motion achieve satisfactory results. Failure is highly probable in irreparable tears and in the presence of significant hypotrophy of the rotator cuff muscles. PMID- 1289284 TI - Static-dynamic intramedullary nailing (SDIN) in diaphyseal and metaphyseal lower limb fractures. AB - The authors report their experience with the Grosse-Kempf nail in treatment of diaphyseal and metaphyseal fractures of the femur and tibia. The biological and biomechanical preconditions of the method as well as several details of the surgical technique are discussed, and the results of 70 procedures performed from 1986 to 1989 are evaluated. The outcomes are quite positive and confirm other reports in the literature. PMID- 1289285 TI - Treatment of slipped capital femoral epiphysis: evaluation of the results of extracapsular epiphysiodesis and open reduction-epiphysiodesis. AB - The authors review 26 patients who underwent either "in situ" extracapsular epiphysiodesis or intracapsular reduction followed by epiphysiodesis for slipped capital femoral epiphysis (SCFE). A total of 32 operations were performed. In the first group (chronic grade II SCFE), no complications occurred in the 16 operations and the results were excellent in all cases. In the second group (chronic grade II and III SCFE and acute-on-chronic SCFE), in 16 operations we observed four cases of avascular necrosis, two of which accompanied by chondrolysis. Three of these were in cases of acute-on-chronic SCFE. The results confirm that the cases of acute-on-chronic SCFE have the worst prognosis and a much higher risk of avascular necrosis and/or chondrolysis than purely chronic SCFE. Early diagnosis of ischemic complications make it possible to maintain the spherical shape of the femoral head and good joint function. The results are considerably better than in untreated cases. PMID- 1289286 TI - The ultrastructure of peripheral neurofibroma: the role of mast cells and their interaction with perineurial cells. AB - The authors analyze the ultrastructure of mast cells and perineurial cells when both are present in neurofibroma of the nerve sheath. Samples of pathologic tissue taken from three patients with neurofibroma of a peripheral nerve sheath were analyzed by light and transmission electron microscopy. The observations document the characteristics of the tumor cells (Schwann cells and perineurial cells) as well as the presence of numerous mast cells, typically in close contact with the perineurial cells and never with the Schwann cells. Many electron-dense vesicles were found between the cells; these vesicles are created when the cell membrane of the mast cell buds, and then they come into contact with the adjacent perineurial cell. Endocytosis vesicles are often present in the cytoplasm of perineurial cells. Analysis of these observations led the authors to assume the existence of a metabolic interaction between the two cell type in contact with each other and an active role of the mast cells in the evolution of the tumor. The following two theories are plausible: either the mast cells actively stimulate tumor growth, or they alter the phenotype of the tumor cell. These findings could have interesting clinical applications. The use of treatment protocols which inhibit mast cell activity could, in theory, stop either the proliferation of the neurofibroma or its malignant transformation. PMID- 1289287 TI - Bone scan features in spontaneous knee pain. AB - In 21 patients with "spontaneous" knee pain, 99mTc-MDP bone scan was found to be more sensitive than clinical and radiographic examination in detecting alterations of the joint components. These alterations were shown by increased radionuclide uptake in the compartments where pain was present, which was most commonly the medial femorotibial compartment, although the femoropatellar compartment was also frequently affected. The authors conclude that bone scan should be the first imaging study performed on the knee in order to establish if further tests are necessary. PMID- 1289288 TI - External callus development on ultrasound and its mechanical correlation. AB - The authors compare the variations in the ultrasonographic and radiographic images with the strain gage values in long bone fractures treated by external fixation. The three test parameters were applied during the entire healing process of 239 fractures. There is a direct correlation between ultrasonographic changes and the calcification of the periosteal callus; there is also a correlation between the morphologic development visible on ultrasound and the stage of the callus. The strain gage values recorded were consistent with these variations. PMID- 1289289 TI - Primitive synovial chondromatosis of the hip joint. AB - Primitive synovial chondromatosis of the hip is quite rare. Through the presentation of four new cases, the authors discuss the pathologic and clinical features of this disease and evaluate the performance of imaging studies, emphasizing the value of CT scan for confirmation of radiographic findings. The indication for surgical treatment is analyzed for each stage of the disease. PMID- 1289290 TI - Kinematic and isokinetic evaluation of patients with flat foot. AB - In recent years research into joint physiology and biomechanics of movement has employed high-technology instruments to quantify the parameters which determine whether the behavior of a joint or kinematic chain is normal or pathologic. Motion analysis, featuring evaluation of both kinematics and the foot-ground reaction, enables us to measure the temporal and quantitative events of normal and pathologic gaits. The use of motion analysis in the study of flat foot has confirmed the ability to discriminate between "normal" and pathologic. Analysis of these themes has enabled us to follow the temporal evolution of the quantitative parameters both before and after treatment, which can be either surgical or conservative. Evaluation of the kinematic changes and the foot-ground reaction also provides information about the quality and effectiveness of the corrective treatment. For instance, the change in the subtalar alignment following application of an endo-orthotic implant can be targeted for validation by motion analysis. All of the joints comprised in the kinematic chain of the lower limb work together to achieve a symmetrical, rhythmic, and most of all harmonic gait. PMID- 1289291 TI - Early diagnosis of deep vein thrombosis following total hip replacement using impedance plethysmography: advantages and limitations of this approach. AB - Early diagnosis of deep vein thrombosis (DVT) following total hip replacement is of fundamental importance given the particularly high incidence of thromboembolic complications and the limited effectiveness of available preventive measures. The authors report the results of postoperative monitoring of the lower limbs using impedance plethysmography (IPG). The validity of the computerized plethysmograph used in this study has been confirmed by previous clinical studies, in which this instrument demonstrated high sensitivity and specificity of diagnosis of deep vein thrombosis in the symptomatic patient. In the present study, however, the instrument is applied to a group of mostly asymptomatic patients, many of whom have non-occlusive DVT. One hundred thirty-two patients underwent IPG both one the day before surgery and on the seventh day after surgery. The postoperative IPG was positive in seven asymptomatic patients (5.3%). Proximal DVT was confirmed by phlebography in five patients (3.7%) and found to be absent in two patients (false positives: 1.5%), for a positive predictive value of 71%. IPG also found proximal DVT to be absent in three patients with postoperative signs and/or symptoms compatible with a thrombotic complication in the lower limbs. The character of the study did not permit collection of data as to IPG sensitivity in the asymptomatic patient, which is presumably quite lower than in the symptomatic patient. Therefore, phlebography remains the most reliable test for diagnosis of asymptomatic DVT. However, systematic monitoring by phlebography is not feasible for logistic, economic, and ethical reasons. Postoperative use of IPG may at least partially reduce the risks connected with thromboembolic complications. PMID- 1289292 TI - Ultrasound for early diagnosis of hip dysplasia. AB - Over the past several years ultrasound has become the main means of early diagnosis of hip dysplasia. The success of this diagnostic test lies in the fact that it is non-invasive, can be performed at a very early age, and can be repeated. Moreover, it has made a more modern nosographic approach to this disorder possible, especially regarding correct orthopedic treatment. The results of the first 1500 patients (3000 hips) examined with ultrasound confirm the validity of our classification, which is based on both anatomical and clinical criteria. When performed correctly, ultrasound examination permits early diagnosis, precise anatomical differentiation, and monitoring of the progress of conservative treatment especially in cases of congenital dislocation treated with the Hoffmann-Pipino harness. PMID- 1289293 TI - Morphological aspects of the synovial membrane and femoral epiphyseal cartilage in experimentally induced chronic anemia. AB - The authors describe the microscopic and ultrastructural changes in the synovial membrane and femoral growth cartilage in experimentally induced chronic anemia. The reiterated anoxic stimulus is responsible for premature morphologic changes which become progressively worse and then appear to stabilize after 30 days. The series of events at the completion of the experiment are characterized by the following: 1) villous hyperplasia-hypertrophy with an increase of the secretory vesicles of type B synoviocytes in the intima and lymphoplasmacellular infiltrates in the sub-intima of the synovial membrane with fragmentation of the bony trabeculae, 2) areas of premature closure of the growth cartilage, 3) irregularity of the profile, thickness, and structure of the articular cartilage. The authors propose a biologic correlation between the above osteoarticular changes and the typical features of certain disorders of this anatomical region (hemopathies, Legg-Calve-Perthes disease). PMID- 1289294 TI - A case of rupture of the deep tendon of the third palmar interosseous muscle. AB - The authors present a case of traumatic subcutaneous rupture of the deep tendon of the third palmar interosseous muscle. This injury is characterized primarily by the abduction of the little finger. Surgical fixation of the proximal loose end of the tendon to the base of the proximal phalanx yields excellent clinical and functional results. PMID- 1289295 TI - Effect of different fractions of methanolic extract of the seeds of Dolichos biflorus on some microorganisms. AB - Extracts from different parts of plants (1) including seeds are reported to act upon pathogenic microorganisms. A few active principles were isolated. The present preliminary report shows significant role of the seeds of Dolichos biflorus (Linn), locally known as Kulthi, against some test organisms using different fractions of defatted seed extracts with methanol. PMID- 1289296 TI - In vitro evaluation of three topical antimycotics against ring-worm fungi singly and in combination. AB - Three antimycotic drugs, viz., Miconazole nitrate, Econazole nitrate and ciclopirox olamine were tested singly and in combination of miconazole nitrate and Econazole nitrate, Miconazole nitrate and Ciclopirox olamine, and Econazole nitrate and Ciclopirox olamine to evaluate in vitro efficacy against Trichophyton mentagrophytes and Macrosporum nanum. The best efficacy was shown by Ciclopirox olamine (MIC 0.78 microgram/ml) and a combination of Miconazole nitrate and Econazole nitrate (MIC 0.78 microgram/ml). PMID- 1289297 TI - Safety assessment of injectable neomycin in calves. PMID- 1289298 TI - Professor M. Jeersannidhi Narasimhan birthday centenary (1891-1991). PMID- 1289299 TI - Comparative mutagenic effect of antifungal antibiotic cycloheximide and cyclophosphamide in three different assays. PMID- 1289300 TI - Screening and identification of antibiotic producing strains of Streptomyces. AB - About 450 actinomycetes were isolated from nearly 100 soil samples collected from different parts of West Bengal. The isolates were screened on the basis of their inhibitory effect against test organisms. Finally two potent antibiotic producers were chosen having maximum inhibitory effect on both gram positive and gram negative test bacteria. On the basis of morphological, structural, physiological and biochemical characters, the two potent antibiotic producers were identified as Streptomyces violaceus-niger and S. antibioticus. PMID- 1289301 TI - In vitro evaluation of lingering antimycotic effect of 2% miconazole nitrate cream (citaderm) on human skin. AB - An evaluation of lingering antimycotic effect of miconazole nitrate cream 2% was evaluated on the skin of 20-healthy subjects (16 male and 4 female) after a single dose of application. The test spots were covered with bandage. The tape strippings were taken at various intervals of time from the test area, and applied on the agar surface which was priorly inoculated with Trichophyton mentagrophytes isolated from a patient with the symptoms of onychomycosis. The lingering effect of miconazole nitrate was determined by the degree of inhibition of growth of the fungus under the tape. The test drug showed lingering effect from 36 to 48 hours. PMID- 1289302 TI - Production of carbohydrases by Sclerotium rolfsii. AB - Coproduction of alpha-amylase, beta-amylase, amyloglucosidase, cellulase, xylanase, pectinase and beta-galactosidase by Sclerotium rolfsii was studied on various polysaccharides. Starch induced alpha-amylase, beta-amylase, amyloglucosidase and beta galactosidase; cellulose induced cellulase, xylanase, pectinase and beta-galactosidase; and pectin induced pectinase and beta galactosidase. None of the enzymes studied except beta-galactosidase were induced on xylan. Group controlled mechanism for production of carbohydrases by Sclerotium rolfsii is suggested. PMID- 1289303 TI - Therapeutic drug monitoring: lithium levels. PMID- 1289304 TI - Therapeutic drug monitoring: lithium levels. PMID- 1289305 TI - With a look at the past, osteopathic medical education heads into its second century. PMID- 1289306 TI - History of osteopathic medical education accreditation. PMID- 1289307 TI - Undergraduate osteopathic medical education. PMID- 1289309 TI - Income and expenditures of osteopathic medical colleges. PMID- 1289308 TI - Financial assistance resources for osteopathic medical students. PMID- 1289310 TI - Osteopathic graduate medical education. AB - Osteopathic graduate medical education is still in transition. The AOA Department of Education will continue to monitor and report on the impact of these changes. PMID- 1289312 TI - Research programs of the AOA and their role in osteopathic medical education. PMID- 1289311 TI - AOA continuing medical education. PMID- 1289313 TI - Four approaches to using patients to teach and evaluate clinical skills of residents, interns, and students. AB - As osteopathic medical educators look for ways to enhance their training programs in a fiscally responsible manner, previously underused training methods deserve a second look. This article presents four ways that patients can serve as teachers and evaluators of residents' and students' clinical skills. PMID- 1289314 TI - Special considerations for HIV infection in women. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1289315 TI - Pregnancy in the workplace. PMID- 1289317 TI - More on discount advertising. PMID- 1289316 TI - Comments on biocompatible osteoconductive polymer. PMID- 1289318 TI - Questions "push" for vaccination against Borrelia burgdorferi infection. PMID- 1289319 TI - Comments on council report. PMID- 1289320 TI - Comments on council report. PMID- 1289321 TI - Comments on council report. PMID- 1289322 TI - Comments on council report. PMID- 1289323 TI - Comments on council report. PMID- 1289324 TI - Comments on council report. PMID- 1289325 TI - Comments on council report. PMID- 1289326 TI - Radiation technology to help break cycle of foodborne disease. PMID- 1289327 TI - Use of computer telecommunications in veterinary medicine. PMID- 1289328 TI - Radiation processing of food. PMID- 1289329 TI - Changing dimensions of veterinary medical education in pursuit of diversity and flexibility in service to society. PMID- 1289330 TI - Clients take our measure. PMID- 1289331 TI - Consolidation: the key to economy of operation and quality service. PMID- 1289332 TI - Effects of blood contamination on equine peritoneal fluid analysis. AB - Peritoneal fluid and blood was collected from 8 healthy adult horses. Four 1-ml aliquots of peritoneal fluid from each horse were then contaminated with 0 ml (normal), 0.05 ml (1 drop), 0.10 ml (2 drops), and 0.20 ml (4 drops) of blood from the same horse. Samples were analyzed for RBC count, nucleated blood cell count, total protein concentration, and nucleated cell differential count. Statistical analysis revealed no significant changes in nucleated cell number, nucleated cell differential, or total protein concentration in peritoneal samples contaminated with blood. The RBC count significantly increased with blood contamination. It was concluded that up to 17% blood contamination of peritoneal fluid in clinically normal horses did not significantly alter interpretation of the nucleated cell count or protein concentration. PMID- 1289333 TI - Production, characterization, and applications of a murine monoclonal antibody to dog erythrocyte antigen 1.1. AB - A murine IgM monoclonal antibody, which recognizes dog erythrocyte antigen (DEA) 1.1, has been produced. The antibody correctly identified canine RBC possessing DEA 1.1 in a panel of RBC typed by an independent laboratory. Reactivity of the monoclonal antibody was compared with canine anti-DEA 1.1 antiserum with 163 RBC samples from 145 dogs. Results of agglutination tests with the 2 reagents were in agreement for all samples. A card agglutination test that uses the monoclonal antibody with blood is described. A monoclonal antibody-based test should facilitate blood typing for DEA 1.1 in clinical practice. PMID- 1289334 TI - Effect of flunixin meglumine and cimetidine hydrochloride on the pH in the third compartment of the stomach of llamas. AB - A Tigon fistula was surgically implanted into the third compartment of the stomach of 5 llamas to allow measurement of gastric pH. The llamas were allotted into 2 groups and given flunixin meglumine or cimetidine hydrochloride for 3 days. After 4 days without treatment, the drugs given to each group were reversed. Measurements of gastric pH were taken every 30 minutes for 6 hours, using an automated pH meter. The pH measurements after drug administration were compared with measurements obtained during a pretreatment control period. Gastric pH during pretreatment control periods had a mean of 1.43 +/- 0.063 (mean +/- SE). The use of flunixin did not significantly decrease gastric pH, compared with pretreatment controls. Gastric pH was significantly higher within the first 30 minutes after administering cimetidine, compared with pretreatment controls, but this difference disappeared at all later times. PMID- 1289335 TI - Abomasal luminal pressure in cattle with abomasal volvulus or left displaced abomasum. AB - The abomasal luminal pressure was determined during surgery in 54 dairy cows with abomasal volvulus (AV) and another 50 dairy cows with left displaced abomasum. The luminal pressure was high in all cattle with AV and 49 (98%) cattle with left displaced abomasum. Luminal pressure was significantly higher in cattle with AV (median, 11.7 mm of Hg; range, 4.1 to 32.4 mm of Hg) than cattle with left displaced abomasum (median, 8.7 mm of Hg; range, 3.5 to 20.7 mm of Hg). Among cattle with AV, abomasal luminal pressure was significantly higher in cattle that died or were sold for slaughter following surgery (median, 20.6 mm of Hg; n = 8) than in cattle that were retained in the herd (median, 11.0 mm of Hg; n = 46). The luminal pressure was weakly correlated with the preoperative serum alkaline phosphatase activity but not correlated with duration of inappetence before surgery. Calculation of likelihood ratios and construction of a response operating characteristic curve for cattle with AV indicated that a cut-off value of 16 mm of Hg for luminal pressure optimized the distribution of cattle into productive and nonproductive groups. The sensitivity, specificity, positive predictive value, and negative predictive value of a luminal pressure < 16 mm of Hg in predicting a productive outcome were 0.83, 0.75, 0.95, and 0.43, respectively. PMID- 1289336 TI - Inherited phosphofructokinase deficiency in an American cocker spaniel. AB - A 3-year-old female American Cocker Spaniel with a chronic hemolytic disorder and hemolytic crises was found to have M-type phosphofructokinase deficiency. This inherited erythroenzymopathy and myopathy is commonly diagnosed in English Springer Spaniels, but the family study of this Cocker Spaniel, although supporting an autosomal recessive mode of inheritance, did not reveal any English Springer Spaniel ancestors. Molecular genetic studies did, however, identify the same mutation in this dog as we previously reported in the English Springer Spaniel breed, suggesting that this mutation originated prior to the separation of these 2 breeds. PMID- 1289337 TI - Acute sterile hemorrhagic cystitis after a single intravenous administration of cyclophosphamide in three dogs. AB - Three dogs receiving cyclophosphamide IV as part of a combination chemotherapeutic regimen developed macrohematuria, stranguria, and pollakiuria within 24 hours of administration of the first dose of this drug. An 11-year-old spayed mixed-breed dog with an oral squamous cell carcinoma was administered 250 mg of cyclophosphamide/m2 of body surface, whereas a 4-year-old castrated male Gordon Setter was treated with 100 mg of cyclophosphamide/m2 and a 6-year-old male German Shepherd Dog with a cutaneous hemangiosarcoma was administered 140 mg of cyclophosphamide/m2. Aerobic bacterial culture, antimicrobial susceptibility testing, and urinalysis were performed on urine obtained by cystocentesis from all 3 dogs after hematuria was observed. Sterile hemorrhagic cystitis was diagnosed on the basis of large numbers of RBC in the urine, lack of pathogens on bacterial culturing of urine, and clinical signs. Although cyclophosphamide induced cystitis in dogs has been reported in the literature numerous times, acute episodes developing within 24 hours of administration of the first dose have not been reported in this species with the use of therapeutic doses. Therefore, appropriate precautionary steps should be taken, even when the drug is being administered intermittently. PMID- 1289338 TI - Clinical, echocardiographic, and Doppler imaging characteristics of mitral valve stenosis in two dogs. AB - Mitral stenosis was diagnosed noninvasively by echocardiography and Doppler imaging in 2 Bull Terriers. Two-dimensional echocardiography revealed severe atrial and moderate left ventricular dilatation; severely reduced mitral valve opening excursion; doming of the cranial mitral valve leaflet into the left ventricle during diastole; thickened, nodular cranial mitral valve leaflets; and reduced mitral valve orifice. M-mode echocardiographic findings additionally indicated greatly diminished mitral valve E to F slope and abnormal caudal mitral valve leaflet motion. Color flow Doppler imaging revealed bright bursts of color with aliasing originating from the stenotic mitral valve orifice, extending into the left atrium during systole, and into the left atrium during diastole. Spectral Doppler recordings revealed transvalvular mitral valve gradients and prolonged pressure half-times. Necropsy performed on 1 dog revealed extremely thickened, nodular, and stiff mitral valves with short, thickened, and fused chordae tendineae. The diagnosis of mitral valve stenosis was easily facilitated with diagnostic ultrasonography. PMID- 1289339 TI - Phenobarbital-responsive episodic dyscontrol (rage) in dogs. AB - Episodic dyscontrol (rage) was diagnosed from the clinical history, electroencephalographic findings, and response to oral treatment with phenobarbital in 3 dogs. Clinical features included a mood change heralding aggressive incidents, explosive aggression directed at people or objects, and a postaggressive phase characterized by lethargy and lack of responsiveness. Abnormal electroencephalographic findings included spike activity in the temporal recordings. All 3 dogs responded well to anticonvulsant medication with phenobarbital. PMID- 1289340 TI - Surgical correction of urethral dilatation in an intersex goat. AB - Multiple congenital urethral abnormalities were successfully corrected in a polled goat kid. Anatomic genito-urinary abnormalities identified were paired testes with associated epididymis, ductus deferens, and active endometrial tissue. Blood karyotyping revealed the female state--XX sex chromosomes. This case exemplifies the complex interactions in addition to Y dominant Mendelian genetics that determine reproductive tract development in goats. The resultant intersex state is clinically recognized with greater frequency in polled progeny. PMID- 1289341 TI - Use of an implant for intraosseous infusion as supportive therapy for a Vietnamese pot-bellied pig with urethral obstruction caused by a polyp. AB - A Vietnamese pot-bellied pig with a urethral polyp was supported by total parenteral nutrition given through an intraosseous implant. Peripheral vascular access was difficult to establish and maintain in this anorectic pig, so a pediatric intraosseous implant was placed in the left tibia. Surgical repair of the urethra was not considered possible, and alternative techniques of a functional bypass were unacceptable to the owners, so euthanasia was elected. Histologic examination of the urethra revealed a polypoid structure believed to be similar to benign congenital polyps described in young boys. PMID- 1289342 TI - Cryptococcal pneumonia and abortion in an equine fetus. AB - Cryptococcus neoformans was the causative agent of pneumonia in a 9-month-old equine fetus aborted by a healthy American Paint mare. Endometritis was diagnosed on biopsy, and vaginal specimens obtained for culture were Cryptococcus-positive 1 month following abortion but not 5 months after abortion. Infection resolved without treatment between 1 and 5 months after abortion, and the mare was bred the following year and delivered a live premature foal without evidence of Cryptococcus infection. PMID- 1289343 TI - Idiopathic, aseptic, effusive, fibrinous, nonconstrictive pericarditis with tamponade in a standardbred filly. AB - A Standardbred filly was admitted for evaluation of pleuritis and pneumonia. Heart rate was 80 to 120 beats/min, and the pulse was barely palpable. Thoracic and abdominal ultrasonography and echocardiography revealed substantial pericardial effusion with cardiac tamponade, fibrinous pericarditis, pleural effusion, and ascites. Initial electrocardiography revealed normal sinus rhythm with decreased amplitude of the QRS complexes consistent with pericardial effusion. Following thoracentesis, echocardiogram-guided pericardiocentesis was performed. Bacterial culture yielded no growth from any of the fluids, and bacteria were not seen on cytologic examination. Initial treatment included broad spectrum antibiotic treatments, IV fluid therapy, and anti-inflammatory agent administration. On the basis of negative culture results, an immune-mediated cause was considered, and dexamethasone was instituted in a decreasing dosage regimen. Pericardial effusion, ventral edema, and ascites began to resolve within 3 days after beginning dexamethasone treatment. Thirty days following discharge, the filly was reexamined, and at that time, the prognosis for athletic performance was considered good so the horse was returned to race training. The final diagnosis in this case was idiopathic, effusive, nonconstrictive pericarditis with tamponade. Early identification, clinical understanding, and application of knowledge of the pathophysiologic mechanisms of pericarditis in horses, combined with use of diagnostic aids such as ultrasonography and aggressive therapy consisting of effusion drainage, pericardial lavage, antibiotics that penetrate the pericardium, and corticosteroids when indicated are critical for a successful outcome in horses with pericarditis. PMID- 1289344 TI - Hypothyroidism in a scarlet macaw. AB - A diagnosis of hypothyroidism was confirmed by use of thyrotropin stimulation testing in an imported male scarlet macaw. Clinical signs included delayed molt; uniform, diffuse contour feather loss over the entire body; and excessive fat deposition over the legs and ventral portion of the abdomen. Clinical signs were associated with mild, non-regenerative anemia; mild leukocytosis; heterophilia; hypoalbuminemia; and hypercholesterolemia. Histologic examination of punch biopsy specimens from regions of feather loss revealed ortho- and parakeratotic hyperkeratosis of the epidermis and moderate, widespread vacuolar degeneration and necrosis in the follicular epithelium. The bird failed to respond to provocative thyrotropin stimulation testing. Treatment with L-thyroxine (0.2 micrograms/kg of body weight, q 12 h) resulted in normal feathering, elimination of fat deposits, and adequate serum thyroxine concentrations at 4 and 12 hours after treatment. PMID- 1289345 TI - Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987-1990). AB - Idiopathic inflammatory bowel disease was the diagnosis for 58 dogs and 26 cats, with signs of persistent gastroenteritis, failed responses to dietary trials, and histologic evidence of cellular infiltrates unrelated to other causes of gastrointestinal tract inflammation. Clinical signs of large intestinal dysfunction, watery diarrhea, vomiting, and anorexia with weight loss were common. Nonspecific hematologic, biochemical, and radiographic abnormalities frequently were observed. Mucosal biopsy specimens, obtained endoscopically, were histologically evaluated for severity of mucosal epithelial damage. Mucosal erythema, friability, enhanced granularity, and ulceration or erosion were the predominant endoscopic lesions. Inflammatory bowel disease lesions of moderate severity predominated in the stomach, duodenum, and colon. Lymphocytic/plasmacytic infiltrates were limited to the lamina propria in biopsy specimens from all regions of the gastrointestinal tract. Inflammatory bowel disease commonly is associated with chronic gastroenteritis in dogs and cats. PMID- 1289346 TI - Coccidioidomycosis in llamas in the United States: 19 cases (1981-1989). AB - Coccidioidomycosis was diagnosed in 19 llamas (California, 9; Arizona, 10). All but 1 had a disseminated form, with pyogranulomas principally in the lungs, thoracic lymph nodes, liver, and kidneys. However, lesions were found in tissue specimens from most organ systems. Antemortem diagnosis was based on radiographic evaluation of the lungs, serologic testing, or presence of spherules of Coccidioides immitis in pyogranuloma aspirates, skin scrapings, or biopsy specimens. Animals residing in endemic areas of southwestern United States are at risk, and llamas appear to be highly susceptible to developing disseminated forms of coccidioidomycosis. PMID- 1289347 TI - Pneumonia associated with Salmonella choleraesuis infection in swine: 99 cases (1987-1990). AB - Salmonella choleraesuis was isolated in pure or mixed bacterial cultures from 153 swine necropsied between Jan 1, 1987 and Dec 31, 1990. Pneumonia was seen in 99 of 109 swine from which this bacterium was isolated in the absence of other pathogenic bacteria. Pneumonia was seen more frequently than hepatitis, splenomegaly, or colitis. Pleuropneumonia that was grossly indistinguishable from the pleuropneumonia associated with Actinobacillus pleuropneumoniae was seen in 29 of 99 swine from which S choleraesuis was the only bacterium isolated. PMID- 1289348 TI - What is your diagnosis? Malarticulation with kyphosis and scoliosis of the cervical vertebral column. PMID- 1289349 TI - Efflux-based antibiotic resistance mechanisms: the evidence for increasing prevalence. PMID- 1289350 TI - Novel membrane proteins present in teicoplanin-resistant, vancomycin-sensitive, coagulase-negative Staphylococcus spp. AB - Clinical isolates of Staphylococcus epidermidis and Staphylococcus haemolyticus resistant to teicoplanin (MIC 64 mg/L) and sensitive to vancomycin (MIC 2 mg/L), were compared with vancomycin- and teicoplanin-sensitive isolates (MICs 1 mg/L) of the same species. No apparent differences between the sensitive and resistant strains of either pair were found with respect to binding of teicoplanin to the bacteria, or to the amino acid content or degree of cross-linkage of purified peptidoglycan. The resistant strains did not inactivate teicoplanin in the surrounding medium. Analysis of the membrane proteins of the resistant S. epidermidis strain grown in the presence or absence of sub-inhibitory levels of teicoplanin (4 mg/L), showed the presence of a 39 kDa protein which was either absent, or present in considerably reduced amounts, in the sensitive strain. Fractionation of cell components after lysis of protoplasts showed that the 39 kDa protein was present predominantly in the membrane fraction but also in small amounts in the wall fraction. Similar investigations with S. haemolyticus revealed the presence of a 35 kDa protein in membranes of the resistant strain: the amount was increased substantially by growth in sub-inhibitory levels of teicoplanin. Membranes prepared by mechanical disintegration of bacteria or by osmotic lysis of protoplasts showed large apparent differences in the amounts of the 39 kDa protein. PMID- 1289351 TI - A beta-lactamase-overproducing strain of Alcaligenes denitrificans subsp. xylosoxydans isolated from a case of meningitis. AB - A resistant (R) clinical isolate of Alcaligenes denitrificans subsp. xylosoxydans was recovered from CSF during treatment including piperacillin. This variant selected in vivo, and a second variant obtained in vitro from the initially susceptible (S) strain, both exhibited resistance to penicillins (ticarcillin, piperacillin) and cephalosporins, but remained susceptible to latamoxef and imipenem. Clavulanate (2 mg/L) restored the susceptibility of the two R-variants to penicillins. A beta-lactamase of pI 9.5 was detected in both S and R strains, but overproduction was observed only in the in-vivo and in-vitro R-variants. This inducible beta-lactamase hydrolysed benzylpenicillin, cephalothin and cephaloridine efficiently, but amoxycillin, ticarcillin and cefoperazone were only moderate substrates. The enzyme was inhibited by clavulanate, cloxacillin and imipenem (IC50 between 3 and 9 mM), but not by aztreonam and chloride ions (1 mM). Resistance to beta-lactams was not transferable by conjugation to Escherichia coli or Pseudomonas aeruginosa, and DNA agarose gel electrophoresis indicated that no plasmid was present in the isolates. Restriction patterns of chromosomal DNA isolated from the S and R isolates were similar after digestion by NotI and HindIII. PMID- 1289352 TI - A non-azole inhibitor of lanosterol 14 alpha-methyl demethylase in Candida albicans. AB - 6-Hydroxy-N-methyl-N-(2-[4-phenylphenyl] ethyl)-1,2,3,4-tetrahydro-1- napthalene methanamine (A60586), a new non-azole inhibitor of ergosterol biosynthesis in Candida albicans ATCC62376 has been identified. In whole cells A60586 produced a dose related reduction of [14C]acetate incorporation into ergosterol and a concurrent increase in the radiolabelling of 4,4-dimethylated sterols. Similar observations were made with [14C]mevalonic acid lactone labelled cell free extracts. The IC50s for inhibition of ergosterol in the whole cell and cell free systems were 22 microM (10 mg/L) and 7.8 microM (3.5 mg/L), respectively. Analysis by gas chromatography of sterols from cells previously incubated at 37 degrees C for 24 h with A60586 (200 mg/L) confirmed the presence of lanosterol and 14 alpha-methyl fecosterol. These data indicate that A60586, inhibits the demethylation of the C-14 methyl group of lanosterol. The MIC of A60586 for several candida strains ranged from 12.5 to 50 mg/L, and against Cryptococcus albidus and Aspergillus niger ranged from 50 to 100 mg/L. The best in-vitro activity of A60586 was against Torulopsis glabrata (MIC range = 3.12 to 50 mg/L). The membrane permeabilizing effect of this compound (50% leakage of [14C]aminoisobutyric acid at 70 mg/L A60586) may have contributed to its in-vitro antifungal activity. PMID- 1289353 TI - Growth-rate-independent killing by ciprofloxacin of biofilm-derived Staphylococcus epidermidis; evidence for cell-cycle dependency. AB - Cell culture methods that allow culture of Staphylococcus epidermidis biofilms at controlled growth rates were used to examine susceptibility to ciprofloxacin. Changes in biofilm susceptibility, dependent upon growth rate, were compared with those for suspended populations grown in chemostat, and also for newly-formed daughter cells shed from the biofilm during its growth and development. Susceptibility increased for intact and resuspended biofilms, and also for planktonic cultures, with increases in growth rate. The dependence of susceptibility upon growth rate was greatest for slow growing cells (mu, 0.01 0.15/h). At any particular growth rate, biofilms appeared more susceptible than their planktonic counterparts. Newly-formed daughter cells were relatively tolerant to ciprofloxacin at all rates of growth. Lack of growth rate dependency for the newly-formed cells suggested a role for the cell-division cycle in determining resistance. This was confirmed by examining the susceptibility of S. epidermidis throughout batch cultures with cell division synchronized. Perfusion of various steady-state biofilms with ciprofloxacin demonstrated killing of the adherent population even at much reduced rates of growth. PMID- 1289354 TI - Effect of biofilm culture upon the susceptibility of Staphylococcus epidermidis to tobramycin. AB - Biofilms of Staphylococcus epidermidis were cultured at various specific growth rates, and susceptibilities to tobramycin were compared with those of equivalent plank-tonic populations. In all instances, susceptibility increased significantly with increasing specific growth rate. However, resuspension of the biofilms increased susceptibility, suggesting some involvement of the glycocalyx in reducing antibiotic permeation of the biofilm. Cells that dispersed spontaneously from the biofilms at steady state were particularly susceptible to this agent. Since such cells correspond to newly-divided daughter cells, the relationship between tobramycin susceptibility and the phase in the division cycle was investigated. Susceptibility was enhanced in cultures dividing synchronously shortly before, during and shortly after cell separation. Perfusion of actively growing S. epidermidis biofilms with tobramycin also demonstrated increased susceptibility with increasing growth rate, but also showed rapid recovery following removal of the agent. PMID- 1289355 TI - Antimicrobial susceptibility of anaerobic bacteria in Australia. AB - The susceptibilities of 900 clinical isolates of anaerobic bacteria to 14 antimicrobial agents were determined by an agar dilution technique. Chloramphenicol, imipenem and metronidazole were found to be active against virtually all of the strains; only a single Bacteroides fragilis isolate was resistant to both imipenem and metronidazole. The addition of clavulanic acid to amoxycillin and ticarcillin potentiated the activities of these agents against all anaerobes including members of the B. fragilis group. Ampicillin/sulbactam and clindamycin were the next most active agents, 91 and 89% of isolates respectively being susceptible. Seventy-three per cent of the bacteria tested were susceptible to cefoxitin and 65% to cefotetan, with the MICs of almost 50% of the isolates clustering between 16 and 32 mg/L. There was also clustering around the breakpoint (64 mg/L) of piperacillin. Azithromycin exhibited poor activity against the B. fragilis group; only 18% of isolates were susceptible to < or = 4 mg/L. However, 92% of non-B. fragilis Bacteroides group strains were susceptible to this agent. We conclude that imipenem, metronidazole, chloramphenicol, ticarcillin/clavulanate, co-amoxiclav and, to a lesser extent, ampicillin/sulbactam are suitable as empirical therapy for infections caused by anaerobic bacteria. PMID- 1289356 TI - Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus. AB - The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections. PMID- 1289357 TI - The activity of hydroxynaphthoquinones against Leishmania donovani. AB - The hydroxynaphthoquinones, buparvaquone, 250C80 and 56W82, showed high activity in vitro against Leishmania donovani amastigotes in mouse peritoneal macrophages, with ED50 values of 0.05, 2.95 and 13.82 microM, respectively. Fourteen other hydroxynaphthoquinones were tested, of which only 566C80 and 608C86 showed significant activity against amastigotes. Buparvaquone, 250C80 and 56W82 were also highly-active against cultured promastigotes. In a BALB/c mouse model, treatment with 100 mg/kg/day for five days with buparvaquone, 250C80 and 566C80 (atovaquone) reduced liver amastigote numbers by 60%, 22% and 30.5%, respectively. PMID- 1289358 TI - In-vivo activity of streptomycin and clofazimine against established infections of Mycobacterium avium complex in beige mice. AB - Beige mice were challenged with 10(6)-10(7) cfu of Mycobacterium avium intracellulare strain 101 and 22 days later treated with streptomycin 150 mg/kg/day alone, clofazimine 20 mg/kg/day alone, streptomycin 150 mg/kg/day plus clofazimine 20 mg/kg/day, or no antimicrobial agent (untreated controls). Both single-drug therapies partially reduced the cfu counts in spleen, liver and lungs compared with the controls however the combination was significantly more effective and completely eliminated the pathogen from the spleen and lungs of some animals after eight weeks treatment. PMID- 1289359 TI - A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies. AB - Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient. PMID- 1289360 TI - Cost-effectiveness of single dose cefotaxime plus metronidazole compared with three doses each of cefuroxime plus metronidazole for the prevention of wound infection after colorectal surgery. AB - The cost-effectiveness of prophylaxis for colonic surgery with single dose cefotaxime plus metronidazole has been compared with that of three doses each of cefuroxime plus metronidazole, by analysing data from a previously published study supplemented with additional data on the hospital and community costs of wound infection after colonic surgery. The original trial included 942 patients having elective colonic surgery in 14 hospitals. The data on costs of wound infection were collected from a further 124 patients undergoing elective colonic surgery at Ninewells Hospital. All these patients received a three dose regimen of cefuroxime plus metronidazole. The Dundee patients received three injections of 0.75 g cefuroxime at 8-hourly intervals whereas the trial patients received a single dose of 1.5 g followed by two further doses of 0.75 g at 8-hourly intervals. The cefuroxime prophylaxis regimen used in the trial cost 24.16 pounds per patient more than the cefotaxime regimen. The components of the excess cost were drugs (15.18 pounds), equipment (6.14 pounds) and staff time (2.84 pounds). The median cost to the hospital of a wound infection was 978.04 pounds (95% CI 482.04 pounds to 1521.22 pounds). The components of the hospital cost of wound infection were: hotel costs 858 pounds (88%), dressing costs 83.02 pounds (8%) and drug costs (excluding prophylaxis) 37.02 pounds (4%). Only five patients received additional antibiotic treatment in the community, and only one required home visits from the District Nurse. Applying the difference in costs of prophylaxis as 21 pounds (costs of drugs plus equipment) and the cost per wound infection as 1000 pounds to the observed wound infection rate of 7% in the cefuroxime group, the wound infection rate in the cefotaxime group would have to be 2.1% higher for the two regimens to be equally cost-effective. The probability that such a difference in efficacy exists is 0.088. A model was developed to calculate the probability of equal cost-effectiveness over a range of costs of wound infection. PMID- 1289361 TI - Vancomycin peak concentration and ototoxicity prevention. PMID- 1289362 TI - A comparison of the costs of ceftazidime therapy and gentamicin combinations. PMID- 1289363 TI - Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood. PMID- 1289364 TI - Beta-lactam and aminoglycoside resistance among Enterobacteriaceae. PMID- 1289365 TI - Penetration of ciprofloxacin into synovial fluid after oral dosing. PMID- 1289366 TI - A prospective study of the effects of oral probenecid on the pharmacokinetics of intravenous ticarcillin in patients with cystic fibrosis. PMID- 1289367 TI - Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function. AB - OBJECTIVE: Some phosphodiesterase (PDE)-inhibitors are believed to alter platelet count and function due to changes in intracellular cAMP. Whether newly developed (specific) PDE-inhibitors negatively influence platelet function in cardiac surgery should be investigated in a randomized study. METHODS: Eighty patients undergoing aorto-coronary bypass grafting were divided into 4 groups and received either the new PDE-III-inhibitor piroximone (group 1), the PDE-III-inhibitor enoximone (group 2), epinephrine (group 3) or no inotropic support (control). PDE III-inhibitors were given as a bolus followed by infusion until starting of cardiopulmonary bypass (CPB). In addition to platelet count and a thrombelastogram, platelet function was assessed by aggregometry (ADP, epinephrine, collagen). Measurements were done before, during and after CPB until the 1st postoperative day. RESULTS: Platelet count and postoperative blood loss did not differ between the groups within the entire investigation period. Maximum aggregation and maximum gradient of platelet aggregation to all stimuli were not changed by either PDE-inhibitor enoximone or piroximone. CPB resulted in a significant decrease of all aggregation variables which was without differences due to treatment. Platelet aggregation recovered in the post-bypass period and exceeded baseline values on the 1st postoperative day. CONCLUSION: It is concluded that enoximone and the new PDE-III-inhibitor piroximone do not affect platelet function and can be used before CPB without risking platelet-related bleeding in cardiosurgical patients in the perioperative period. PMID- 1289368 TI - Cerebral blood flow and cerebral oxygen consumption in patients with COPD on mechanical ventilation. AB - OBJECTIVE: To investigate the effect of PaCO2 on cerebral blood flow (CBF) in chronic obstructive pulmonary disease (COPD). DESIGN: Before-after trial. SETTING: General ICU in a regional hospital. PATIENTS: 7 patients undergoing mechanical ventilation because of an exacerbation of COPD. INTERVENTION: CBF and cerebral metabolic rate of oxygen (CMRO2) of COPD were measured before and after hyperventilation and were compared by those of normal patients. CBF was measured by the Kety-Schmidt technique using 15% N2O. MEASUREMENTS/RESULTS: Hyperventilation produced a significant reduction in CBF in COPD with no concomitant change in CMRO2. CMRO2 in COPD was significantly lower than those in normal patients. The regression equation was shifted significantly more to the right in COPD. CONCLUSION: The sensitivity of CBF in CO2 remained but CMRO2 was reduced markedly in COPD patients. PMID- 1289369 TI - The effect of selective decontamination of the digestive tract on gastrointestinal enterococcal colonization in ITU patients. AB - OBJECTIVE: The effect of selective decontamination of the digestive tract (SDD) on Intensive Therapy Unit (ITU)-acquired enterococcal infection and colonization was studied. Changes in the predominant species isolated and resistance patterns to antimicrobial agents were also studied. DESIGN: Three groups were investigated: historical control (HC), contemporaneous control (CC) and patients receiving SDD (topical polymyxin, amphotericin B and tobramycin throughout ITU stay with intravenous ceftazidime for the first 3 days only). SETTING: Adult general ITU with 7 beds. PATIENTS: Patients with a nasogastric tube in situ and who were likely to remain in ITU for 48 h or longer were recruited. RESULTS: Enterococcal infections occurred in 3 of 84 HC patients and 2 of 91 CC patients. There were no unit-acquired enterococcal infections in the SDD group. There were 140 episodes of enterococcal colonization occurring in 112 patients, with significantly more in the SDD and CC groups (p < 0.05. There were no significant differences in antibiotic sensitivities between the three groups. Enterococcus faecalis was the most frequently isolated species. CONCLUSION: SDD does not predispose to enterococcal infection but does encourage colonization in patients receiving the regimen and other patients in ITU at the same. There is a complex interaction of factors which influence faecal flora and the likelihood of patients becoming colonized or infected with enterococci. PMID- 1289370 TI - Electron-microscopic description of accretions occurring on tips of infected and non-infected central venous catheters. AB - OBJECTIVE: The purpose of the study was do describe the architecture of accretions occurring on the tips of central venous catheters (CVC). DESIGN: A conservative procedure was used followed by two different techniques of electron microscopy. SETTING AND PATIENTS: the study included 19 catheters which have been used on intensive cared adults, and which were chosen among those of parallel 300 CVC study. MEASUREMENTS AND RESULTS: CVC were considered sterile, contaminated, colonized or infected according to microbiological and clinical criteria. CVC were found to remain much cleaner than in past descriptions. When present, accretions were located on the olive-shaped end, and displayed stratified structures with three types of material: amorphous material, thrombus components and inflammatory cells. Bacteria were not seen, even on culture positive CVC. Candida albicans was found on one CVC in the cytoplasm of granulocytes, and made no direct contact with the plastic surface. CONCLUSION: This technique should contribute to the understanding of the pathobiology of CVC infection and provide information proving or precluding the involvement of microbial adherence to polymers in vivo. PMID- 1289371 TI - Possible risk for cardiac arrhythmia related to intravenous erythromycin. AB - OBJECTIVE: To evaluate the incidence of prolongation of the rate-corrected electrocardiographic QT interval (QTc) and of ventricular arrhythmia associated with intravenous administration of erythromycin lactobionate. DESIGN: A consecutive series of 7 critically ill patients treated with intravenous erythromycin for severe pneumonia. SETTING: A medical intensive care unit of a university hospital. MEASUREMENTS AND RESULTS: Registration of QTc duration before and after intravenous administration of erythromycin as a short infusion. Blood chemistry, hemodynamic variables, arrhythmias, and co-medications were recorded. Evaluation of at least 10 ECG intervals by 2 experienced investigators who were blinded as to the time of drug administration. If several measurements were performed in the same patient, only the mean value was used for further analysis. During 12 of 13 drug administrations studied in 7 patients QTc prolongation was observed. The extent of QTc prolongation was significantly correlated with the infusion rate (mg/min, r = 0.765, p = 0.05). In 3 patients ventricular arrhythmia occurred in close temporal relation to the erythromycin infusion; two of them developed ventricular fibrillation shortly after the first and second dose of erythromycin, respectively, and died within 3 h. CONCLUSION: In critically ill patients erythromycin-induced QTc prolongation is a frequent pharmacologic effect correlated with erythromycin infusion rate. To avoid changes in electrocardiographic intervals and thereby possibly potentially life threatening ventricular arrhythmia administration with the lowest possible infusion rate and close cardiac rhythm monitoring are advisable in these patients. PMID- 1289372 TI - The influence of different levels of PEEP on peripheral tissue perfusion measured by subcutaneous and transcutaneous oxygen tension. AB - OBJECTIVE: To compare subcutaneous (PscO2) and transcutaneous (PtcO2) oxygen tension measurements in relation to hemodynamic variables at different levels of PEEP, and to evaluate the usefulness of these measurements as monitors of peripheral tissue perfusion. DESIGN: Prospective trial. SETTING: Intensive care unit in a university hospital. PATIENTS: Seven patients with gastric cancer who where undergoing total gastrectomy. INTERVENTIONS: Silicone catheter was placed in the upper arm and transcutaneous oxygen monitor was placed on the upper part of the chest. A pulmonary artery catheter was placed in the right pulmonary artery. MEASUREMENTS AND RESULTS: PscO2 and PtcO2 together with hemodynamic variables were measured at different levels of PEEP. Progressive increase of PEEP reduced cardiac index (CI) (p < 0.05) with a concomitant decrease of PscO2 (p < 0.05) and oxygen delivery (DO2) (p < 0.05). Changes in PtcO2 paralleled changes in arterial oxygen tension (PaO2), but no correlation was found between PtcO2, CI and DO2. CONCLUSION: PscO2 is a sensitive indicator of subcutaneous tissue perfusion, which can be used to identify the PEEP level, with optimum peripheral perfusion. PscO2 seems to be a more reliable indicator of tissue perfusion than PtcO2. PMID- 1289373 TI - Differential lung ventilation with a double-lumen tracheostomy tube in unilateral refractory atelectasis. AB - Two patients with refractory hypoxemia due to unilateral lung atelectasis were treated with differential lung ventilation (DLV) through a Robertshaw-type, double-lumen tracheostomy tube. DLV was applied using two non-synchronized ventilators and maintained for 6 and 3 days, respectively. Ventilator settings were chosen in accord to the clinical, laboratory and chest X-rays results. Particularly, tidal volume and PEEP were set to avoid excessively high alveolar pressure and to obtain the highest possible value of compliance. We investigated the mechanical properties of the two lungs separately by measuring airway pressure and compliance of each lung before the beginning of DLV and at 0, 5, 24, and 48 h after. Initially we observed in both patients very low values of compliance (7-9 cm H2O/l) and a significant level of PEEPi (12-8 cm H2O) of the diseased lung, whereas PEEPi in the healthy lung was negligible. The clinical improvement was assessed by sequential chest X-rays and by significant improvement of arterial blood gas and PaO2/FiO2 ratios and was associated with a progressive increase of compliance (24-22 cm H2O/l) and by a fall of PEEPi levels (5-4 cm H2O) of the diseased lung. We also observed an improvement of SvO2, O2AVI, PVRI and Qva/Qt values (Case 1). The tracheostomy tube used to apply DLV was very reliable, allowing easy nursing care and selective bronchial aspirations. We conclude that DLV is a very useful technique in unilateral lung pathology, and it can be a life saving procedure in selected patients, by supplying volume and PEEP more efficiently to the affected lung. PMID- 1289374 TI - Failure of thiamphenicol in a penicillin-allergic patient with Listeria meningoencephalitis--delayed cure following penicillin desensitization. AB - A 27-year-old woman, without compromised immunodefenses, experienced a Listeria meningoencephalitis, with brainstem symptoms. The identified agent exhibited poor susceptibility to usual effective antibiotics, except for penicillins. Knowledge of past history of an allergic reaction to beta-lactam antibiotics lead to appropriate therapy after acute intravenous desensitization of the patient to amoxicillin. Treatment resulted in therapeutic administration rate over 24 h, and in rapid regression of clinical and biological disorders. PMID- 1289375 TI - Clostridial sepsis with massive intravascular hemolysis: rapid diagnosis and successful treatment. AB - A 61-year-old man developed a pyrescia accompanied by a massive intravascular hemolysis after abdominal surgery (Whipple's operation) of a pancreatic adenocarcinoma. Abdominal ultrasound and the abdominal CT-scan showed marked aerobilia and multiple liver abscesses. Laboratory tests demonstrated the presence of the Thomsen-Friedenreich cryptantigen (TCA) on the membranes of the patient's erythrocytes. The enzymatic cleavage of N-acetyl-neuraminic acid usually covering the TCA may lead to a life threatening intravascular hemolysis. Since Clostridial bacteriae typically synthesize neuraminidase, the presumptive diagnosis of Clostridial sepsis complicated by massive hemolysis was made. Immediate antibiotic therapy including penicillin G and metronidazole stopped hemolysis within a few hours and the patient servived. On the following day, microbiological examination identified Clostridium perfringens in the patient's blood cultures. Clostrial sepsis should be suspected in patients with underlying infections and/or malignant diseases, particularly of the gastrointestinal or genitourinary tract, who present with septic shock and acute intravascular hemolysis. Whereas microbiological specification of the organism is time consuming, the relatively simple agglutination test with anti-TCA peanut lectin can provide a rapid presumptive diagnosis. The immediate onset of an appropriate antimicrobial therapy is of central importance and might be life-saving. PMID- 1289376 TI - Rare procedures during delivery room resuscitation--cardioversion of ventricular tachycardia in an asphyctic neonate. AB - Successful cardioversion of ventricular tachycardia in a full-term male infant, born severely depressed by emergency Cesarean section 9 min after the mother was given bilateral paracervical bupivacaine blocks for pain relief during normal labor, is described. The apparently stillborn baby was resuscitated by conventional means until electronic heart monitoring revealed transition from asystole to rapid ventricular tachycardia 14 min after birth. At 20 min, cardioversion with 5 watt-second was performed with successful reversion to sinus rhythm. The child recovered rapidly and neurological status at 12 months was normal. Obviously, active search and aggressive management of rapid ventricular arrhythmias are indicated during neonatal resuscitation, if potentially arrhythmogenic drugs are used in perinatal care. PMID- 1289377 TI - Hemodynamic responses to noxious stimuli in brain-dead organ donors. AB - The case report presents evidence for the spinal origin of the marked hypertensive responses to noxious stimuli that may occur in organ donors who fulfill the commonly accepted criteria of brain death. Cardiovascular spinal reflex activity does not invalidate these criteria. For the first time, the catecholamine plasma concentrations have been determined during spinal pressor reflex activity. Circulating epinephrine increased more markedly than norepinephrine in both cases, rising to 4.7 and 44 times the baseline concentration respectively. The relation between plasma norepinephrine and epinephrine suggests involvement of the adrenal medulla in the reflex arc. The literature on spinal hemodynamic reflexes is reviewed. PMID- 1289378 TI - Acute myocardial infarction in a young woman: possible relationship with sustained-release theophylline acute overdose? PMID- 1289379 TI - Concerning the definition of ARDS. PMID- 1289380 TI - Unrecognised chloralose poisoning. PMID- 1289381 TI - The effect of sedation with propofol on postoperative bronchoconstriction in patients with hyperactive airway disease. PMID- 1289382 TI - The trigemino-pupillary reflex: a model of sensory-vegetative integration. AB - Trigeminal stimulation can induce pupillary changes. In vivo and in vitro studies have demonstrated that electrical impulses applied at the trigeminal level can provoke a miotic response, whose nature has been ascribed to the anti-dromic release of neuropeptides (substance P in particular). In order to better define the pupil response to trigeminal stimulation, we investigated the human pupil response to quantified (painless and painful) corneal stimuli by means of a combined (neurophysiological and pharmacological) technique. The response to corneal stimulation was bilateral, direct and consensual. It had a biphasic progression with an initial mydriasis (which directly correlated with the stimulus intensity), followed by a miotic phase. The mydriatic phase disappeared after thymoxamine application, while homatropine pre-treatment prevented occurrence of the miotic phase. The data obtained indicate that the pupillary response to corneal stimulation (trigemino-pupillary reflex) is a multisynaptic reflex with an afferent branch involving the trigeminal system, and an afferent branch involving both the sympathetic and the parasympathetic system. Other pathways, such as the SP-mediated release of acetylcholine, cannot be excluded. Thus the reflex appears to be a potentially useful tool for investigating pain/vegetative interactions in various clinical conditions. In turn, the description of its changes in pathologies characterized by a sympathetic/parasympathetic deficit or by a SP-ergic imbalance will allow us to better describe its inner mechanisms. PMID- 1289383 TI - Hypogastric nerve section reveals a role for both afferent and efferent fibres in the feline continence process. AB - The role of the hypogastric afferent and efferent innervation in the process of urine storage during natural rate filling was examined in the pentobarbitone anaesthetized cat. The observed changes in bladder pressure following hypogastric nerve section demonstrated the presence of baseline sympatho-inhibitory and phasic sympatho-excitatory influences for a significant portion of each distension, which proceeded to a volume just over halfway through the continence process. A reduction in bladder wall compliance at the end of the distensions provided evidence for a net sympatho-inhibitory influence in the second half of the continence phase. Hypogastric nerve section also resulted in a reduction in the reflex increase in hypogastric efferent nerve activity, measured in continuity. This suggested that hypogastric afferent fibres made a significant contribution to the regulation of sympathetic hypogastric nerve activity during natural rate filling. PMID- 1289384 TI - Alteration in sympathetic nerve activity during liver regeneration in rats after partial hepatectomy. AB - To determine if the sympathetic nerve has a role in liver regeneration, the alterations of tissue norepinephrine (NE) content and its turnover were measured in rats after partial hepatectomy. NE content per unit liver mass decreased progressively to about one-fourth of controls by the ninth day after partial hepatectomy. Since the total amount of NE in the whole liver did not change during nine days of liver regeneration, it was supposed that sympathetic innervation could make slower progress than proliferation of hepatocytes. Fractional turnover rate of NE was reduced transiently in regenerating liver 24 48 h after partial hepatectomy and recovered to normal 8-9 days after the operation. Such a transient reduction of NE turnover was observed specifically in the liver. These results suggest that sympathetic nerve activity of the liver is suppressed at the early stage of regeneration. PMID- 1289385 TI - Normal sympathetic nerve activity in a reflex sympathetic dystrophy with marked skin vasoconstriction. AB - Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old patient with reflex sympathetic dystrophy (allodynia, marked vasoconstriction in the ulnar part of the left hand) following Vth finger amputation. Skin sympathetic activity showed normal characteristics with a weak discharge at rest whereas bursts of impulses could be evoked by sympatho excitatory stimuli. Sympathetic bursts induced by painful stimuli were few, also during long-lasting allodynic pain. Sympathetic bursts induced by inspiratory gasps were not associated with excacerbation of pain. The discrepancy between the marked skin vasoconstriction and the low resting sympathetic discharge underlines the fact that sympathetic effector organ hyperactivity (i.e. vasoconstriction and/or hyperhidrosis) cannot be taken as evidence for increased sympathetic discharge. In the present case, the neuropathic pain syndrome cannot be considered as maintained by an increased sympathetic neural discharge to the symptomatic limb. PMID- 1289386 TI - Vagal stimulation and cardiac chronotropy in rats. AB - Increasing frequencies of electrical stimulation of the right vagus nerve in the rat yielded a progressive lengthening of heart periods. Stimulation was capable of driving vagal control of cardiac chronotropy over its full physiological dynamic range, to the point of sinus block. The steady-state transfer function between vagal stimulation frequency and cardiac chronotropy was approximately linear, with a slope of 7.4 ms/Hz. The linearity of the stimulation-heart period function is consistent with previous reports in dogs, rabbits and humans, although the slope of the function was considerably lower in the rat. PMID- 1289387 TI - Cortisol effect on atrial natriuretic factor response to hypertonic saline in fetal sheep. AB - Atrial natriuretic factor (ANF) is released following a variety of stimuli including hypertonicity in the fetus. To study the effect that cortisol has on fetal ANF release, seven chronically instrumented fetal sheep at gestational ages ranging from 110-132 days were studied in two experiments. In one experiment (CORTISOL), a continuous cortisol (with EtOH vehicle) infusion was maintained. In the other experiment (CONTROL), the vehicle was infused alone. Ninety minutes from the start of this infusion, a hypertonic saline bolus (12 meg/kg) was given. Osmolality, ANF, cortisol, pH, PO2, PCO2, mean arterial pressure (MAP), heart rate (HR), and hematocrit (HCT) were followed over a 120-min period. Following hypertonic saline, serum osmolality increased from 290.6 +/- 2.3 mOsm/kg to 310.4 +/- 2.5 mOsm/kg (P < 0.01). Baseline values for pH, PO2, and HCT were 7.37 +/- 0.01, 22.5 +/- 1.6 mmHg, and 33.9 +/- 1.2 respectively. Each of these variables fell following hypertonic saline infusion. MAP rose from 40.6 +/- 1.7 mmHg to 47.0 +/- 2.4 mmHg (P < 0.01). However, there were no differences between CONTROL and CORTISOL experiments in any of the above changes. Cortisol levels in the CONTROL group did not change during the course of the experiment, but in the CORTISOL group rose from 8.2 +/- 4.4 ng/ml to 33.0 +/- 9.9 ng/ml (P = 0.02). Plasma ANF levels prior to hypertonic saline were similar (124.8 +/- 17.7 pg/ml and 127.6 +/- 26.1 pg/ml) in the CONTROL and CORTISOL groups respectively and rose following hypertonic saline to a maximum of 155.3 +/- 16.6 pg/ml and 189.2 +/- 42.7 pg/ml (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289388 TI - Effects of indomethacin on fetal renal function, renal and umbilicoplacental blood flow and lung liquid production. AB - The effects of indomethacin (10 mg/kg i.v. to the ewe and 12 mg/kg i.v. to the fetus) were examined in 8 chronically catheterized fetal sheep (117-138 days gestation). These doses suppressed fetal 6-keto-prostaglandin F1 alpha and thromboxane B2 levels. Fetal arterial PO2 increased (P < 0.01); PCO2 (P < 0.001) and pH fell (P < 0.001) and arterial pressure did not change. Placental blood flow increased in 4 of the 5 fetuses in which blood flows were measured. Lung liquid flow rate fell (P < 0.001). Fetal renal blood flow did not change but its distribution did, i.e. flow to the inner part of the renal cortex decreased (P < 0.05). Urine flow rates did not change but there was a natriuresis (P < 0.02), kaliuresis (P < 0.02) and chloriuresis (P < 0.02). Urinary osmolality rose (P < 0.001) and free water clearance fell (P = 0.004). It is concluded that when indomethacin is administered to both ewe and fetus, the resulting fall in prostaglandin I2 and thromboxane A2 levels causes marked changes in fetal blood gas status, renal function and lung liquid production. These effects are more profound than those seen when indomethacin is given only to the fetus. They do not however, explain the reason why clinical use of indomethacin is associated with a reversible oligohydramnios. PMID- 1289389 TI - Repeated maternal separation in the neonatal rat: cellular mechanisms contributing to brain growth sparing. AB - Separation of neonates from their dam has been shown to evoke acutely a variety of biochemical responses, typified by depression of ornithine decarboxylase (ODC) activity. In the current study where rat pups were removed from their nursing dams for 6 h, ODC activities in the liver, heart, kidney and lung were markedly suppressed, but the enzyme in the brain was not altered during the early postnatal ages. These data suggest that the brain was protected from maternal separation insults, a homeostatic response mediated in part, by an increase of circulating corticosterone and glycogen mobilization from peripheral tissues, particularly the liver. In addition, we examined whether these responses were extended to pups who were subject to repeated episodes of maternal deprivation, and whether this stress paradigm might be associated with corresponding changes of cellular growth and maturation. Pups were removed from their dams for 6 h daily beginning at 4 days of age until weaning at 21 days. Plasma corticosterone levels of the deprived pups were elevated significantly at the end of each stress episode but returned to basal (control) levels subsequently. The repeating stress paradigm did not influence the magnitude of this hormonal response at the ensuing ages. Consistent with findings observed in the single episodes of stress, ODC activities in the peripheral tissues were significantly depressed in pups subject to repeated maternal deprivation, but the enzyme appeared to recover to control levels 18 h after each insult. In contrast, brain ODC activity did not exhibit any change throughout the period examined. Moreover, while ontogenetic gains of DNA and protein in the peripheral tissues of the deprived rats lagged slightly but consistently behind those of controls, these macromolecules in the brain were not affected appreciably. These results thus suggest that brain growth was, by and large, spared from insults associated with repeated maternal separation; but this stressful paradigm did produce marked, though reversible biochemical and physiological responses in the peripheral tissues of neonates, which cumulatively led to a lag of cellular development. PMID- 1289390 TI - Amniotic fluid and plasma glycine/valine ratios in substrate deprived growth retarded fetal rats. AB - Characteristic profiles of the free amino acid concentration in umbilical cord blood of growth retarded newborns have been observed. We hypothesized that the amniotic fluid of growth retarded fetal rats would show an increase in the ratio between glycine and valine which would parallel the pattern observed in the cord blood of growth retarded neonates, thus providing an index for the antepartum identification of the substrate deprived growth retarded fetus. Six test and 6 control dams were tested. Four fetuses per dam, matched for uterine location were examined. Test animals were fasted for 72 hours. Sampling was performed on day 21 under anaesthesia. Fetal size was significantly reduced (P < 0.0001) in the test group. [T = 2.68 gs. +/- 0.28 vs. C = 3.67 gs. +/- 0.25]. Fetal plasma concentrations of glycine showed an increase in test animals (P < 0.01) while valine showed a significant reduction (P < 0.0001). Glycine (pm/microliters) T = 308 +/- 64 vs. C = 269 +/- 47, valine (pm/microliters) T = 424 +/- 79 vs. C = 671 +/- 218]. Amniotic fluid concentrations for both glycine and valine were significantly decreased (P < 0.0001) in test animals. [Glycine (pm/microliters) T = 710 +/- 124 vs. C = 931 +/- 178; valine (pm/microliters) T = 845 +/- 169 vs. C = 1,339 +/- 234]. The glycine/valine ratio was significantly increased (P < 0.01) in both fetal plasma and amniotic fluid in test animals [Plasma T = 0.74 +/- 0.18 vs. C = 0.43 +/- 0.13. Amniotic fluid T = 0.85 +/- 0.08 vs. C = 0.69 +/- 0.09]. Consistent with our hypothesis, the amniotic fluid concentrations generally parallel the observations made in the plasma. This finding could enhance the antepartum identification of the substrate deprived growth retarded fetus. PMID- 1289391 TI - Islet transplantation in diabetic pregnant rats normalizes glucose homeostasis in their offspring. AB - Diabetes of the mother during pregnancy induces alterations in the fetus, resulting in impaired glucose homeostasis in the offspring. In youngsters of severely diabetic mothers, during glucose infusion, hyperinsulinemia is associated with hyperresponsiveness of the beta-cells and insulin resistance. In order to normalize maternal metabolism, isolated islets from neonatal rats were transplanted into the vena porta of severely hyperglycemic (Streptozotocin) rats at day 15 of gestation. Strict glycemic control of the mothers was achieved throughout further gestation and lactation. In the adult offspring of these transplanted rats insulin levels during glucose infusion were significantly lower than in the offspring of sham-transplanted diabetic mothers and were not different from controls. The work confirms that the diabetic state of the mother during late gestation (the period of development of the endocrine pancreas and of the insulin-receptor system) is the inducing factor for the abnormal glucose homeostasis in the offspring, and normalisation of the hyperglycemia eliminates these long-term consequences. PMID- 1289392 TI - The effect of hyperglycemia on acid-base and sympathoadrenal responses in the hypoxemic fetal monkey. AB - We investigated the influence of hyperglycemia on the fetal acid-base and sympathoadrenal responses to hypoxemia (maternal FIO2 9%) in rhesus monkey fetuses. In chronic preparations, we determined PO2, O2 content, PCO2, pH, lactate, glucose, insulin, catecholamines, heart rate, and arterial pressure. Combined hyperglycemia and hypoxemia resulted in a decrease in fetal pH and an increase in lactate; however, the magnitude of these changes was only modestly, and not significantly, greater than those observed during euglycemic hypoxemia. These effects were much less striking than expected, based on earlier work in sheep (Shelley, Bassett & Milner, 1975; Robillard, Sessions, Kennedy & Smith, 1978). Although catecholamines increased significantly in response to hypoxemia both in hyperglycemic and euglycemic fetuses, the increase was less in the hyperglycemic group, possibly resulting from a modulating effect of the high glucose concentration on catecholamine release from the adrenal medulla. Finally, a significant fetal insulin response to hyperglycemia was seen which, suggestively, was partially inhibited in the presence of hypoxemia and its associated increase in sympathoadrenal activity. PMID- 1289393 TI - Interpretation of blood culture results. PMID- 1289394 TI - Interpretation of blood culture results. PMID- 1289395 TI - Transmission of Clostridium difficile. PMID- 1289396 TI - Vancomycin-resistant enterococcus faecium: headline news. PMID- 1289397 TI - Vancomycin-resistant Enterococcus faecium in hospitalized children. AB - OBJECTIVE: Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. DESIGN: Survey; case-control study. SETTING: Children's hospital. PATIENTS: Pediatric oncology patients. INTERVENTION: Contact isolation, restriction of vancomycin prescribing. RESULTS: There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. CONCLUSIONS: Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium. PMID- 1289398 TI - Methicillin-resistant Staphylococcus aureus: a questionnaire survey of 75 long term care facilities in western New York. AB - OBJECTIVES: To determine the frequency of recognition of methicillin-resistant Staphylococcus aureus (MRSA) as an infection control problem and its prevalence among long-term care facilities, and to evaluate whether certain long-term care facility characteristics such as bed size, ownership, level of infection control activity, and frequency of resident transfers to acute care hospitals are related to the recognition or prevalence of MRSA in this setting. DESIGN: Questionnaire survey. SETTING: Seventy-five long-term care facilities in the 8 counties of western New York. RESULTS: Seventy-five of 81 (92.6%) long-term care facilities returned a completed questionnaire. Seventy-nine percent were considered to have a "limited" level of infection control activity (part-time infection control practitioner who spent less than 10 hours a week on infection control activities). The larger the long-term care facility, the more time was spent on infection control activities (p = .01). Seventy-two percent of the long-term care facilities screened new admissions for MRSA by reviewing culture reports; 69% of the long-term care facilities had a specific infection control policy for MRSA. Sixteen of the 75 (21%) facilities felt they had an infection control problem with MRSA. By univariate analysis, the only characteristic significantly associated with this recognition was use of nurse practitioners or physician assistants by a facility (p < .05). Eighty-one percent of the 75 long-term care facilities had identified one or more patients with MRSA in the year prior to the survey. By univariate analysis, the only characteristics that were significantly associated with the number of residents with MRSA were the monthly average number of residents transferred to acute care facilities (p = .034) and facility bed size (p = .022); there was also a trend toward increasing intensity of infection control activities (p = .085). However, facility bed size and the average number of resident transfers per month to acute care facilities were strongly associated (p = .0002). By stepwise logistic regression analysis, only bed size was an independent predictor of the number of residents with MRSA. Many long-term care facilities had tried to eradicate MRSA; ciprofloxacin was most commonly used to eradicate MRSA. CONCLUSIONS: The vast majority of the 75 long-term care facilities in the 8 counties of western New York have identified patients with MRSA, although only a minority (21%) of them actually believed that an infection control problem existed. Facility size (a surrogate for the monthly average number of resident transfers to acute care facilities) seems to be an important factor in determining the number of residents with MRSA in long-term care facilities in our geographic region. The major longitudinal studies of MRSA in such facilities have so far been done only in Veterans Affairs facilities. Further studies are needed in freestanding long-term care facilities, the largest group of long-term care facilities in the United States, to determine the epidemiology of MRSA in this setting and to develop practical and valid infection control methods for residents with MRSA. PMID- 1289399 TI - Healthcare workers' risk of contact with body fluids in a hospital: the effect of complying with the universal precautions policy. AB - OBJECTIVE: To test whether healthcare workers' knowledge of and compliance with the basic principle of the Universal Precautions policy (i.e., that all patients should be treated equally regarding contact with body fluids) influenced the rate of contact with patient blood. DESIGN: Survey based on anonymous questionnaires. SETTING: A 380-bed secondary and tertiary care hospital receiving emergency and elective patients. PARTICIPANTS: All employees having any contact with patients. Nine hundred one of 1,308 (69%) of the questionnaires were returned. RESULTS: Twelve percent of the respondents (95% confidence interval [CI95] = 10.0%-14.4%) had experienced any contact with patient blood in the week preceding their answer. Physicians had the highest rate of contact with blood followed by nurses. In the five groups--physicians, nurses, laboratory technicians and phlebotomists, nursing aides, and student nurses--contact with blood was less frequent in the subgroup that did know and comply with the basic principle of the Universal Precautions policy, compared with the subgroup that did not. When adding the results for the 5 groups, contact with blood was experienced by 91 of 571 (15.9%, CI95 = 13%-19%) of the personnel who did not know and comply with Universal Precautions. The personnel who did know and comply with Universal Precautions had a significantly lower (9 of 111 [8.1%], p < .05, CI95 = 3.8%-15%) rate of contact with blood. CONCLUSIONS: The healthcare workers who knew and complied with Universal Precautions had a significant lower rate of contact with patient blood than those who did not. PMID- 1289400 TI - Methicillin-resistant Staphylococcus aureus in hospitals and long-term care facilities: microbiology, epidemiology, and preventive measures. PMID- 1289401 TI - Group A streptococcal outbreaks in nursing homes. PMID- 1289402 TI - Two outbreaks of primarily noninvasive group A streptococcal disease in the same nursing home, New York, 1991. PMID- 1289403 TI - Using force field analysis to promote use of personal protective equipment. PMID- 1289404 TI - National surveys cite personal safety as the number one on-the-job concern of nurses. PMID- 1289405 TI - Nationwide screening program launched to identify individuals infected with hepatitis B and C. PMID- 1289406 TI - The ultrastructure of the noninvolved urothelium of tumor-bearing patients before and after interferon treatment. AB - The ultrastructural morphology of the noninvolved urothelium of tumor-bearing patients before and after interferon-alpha 2b (IFN-alpha 2b) treatment was investigated. The ultrastructure of the normal bladder urothelium has been reported. The noninvolved urothelium of our patients already showed deviation from the normal. At the end of therapy, we noted a partial restoration of the urothelium to its normal morphology with the reestablishment of some of its normal features, i.e., a well-developed Golgi apparatus, the existence of parts of the asymmetric unit membrane, and the appearance of nuclear bodies. Prevention of tumor recurrence by restoring the ultrastructural morphology of the noninvolved urothelium with IFN-alpha 2b is a subject worthy of further investigation. PMID- 1289407 TI - Interferon-alpha/beta, pentoxifylline, and caffeine synergize with interferon gamma to induce major histocompatibility complex class I expression on a constitutively class I-negative murine tumor cell line. AB - The constitutively class I-negative tumor cell line, Kgv, expresses H-2Dk in response to interferon-gamma (IFN-gamma), but not in response to IFN-alpha/beta, tumor necrosis factor, or lymphotoxin. H-2Dk expression was not induced on Kgv cells by the methylxanthines, pentoxifylline (PTX) and caffeine, which modulate class I expression on cells that constitutively express class I molecules. Treatment of Kgv cells with either IFN-alpha/beta, PTX, caffeine, or dibutyryl cAMP and a concentration of IFN-gamma insufficient by itself to induce Dk expression resulted in the induction of Dk expression. Since PTX and caffeine are cAMP-specific phosphodiesterase inhibitors, it is possible that the effects of PTX, caffeine, and dibutyryl cAMP involve a cAMP-dependent mechanism. We conclude that concentrations of IFN-gamma insufficient to induce Dk expression on Kgv cells may be capable of rendering the Dk gene responsive to signals that, in the absence of IFN-gamma treatment, have no effect on Dk expression. PMID- 1289408 TI - Absence of biological effects of orally administered interferon-beta ser. AB - To assess biological effectiveness of interferon (IFN) administered orally, we measured serum IFN and several proteins and metabolites induced by IFN after oral administration of 2.5 mg or 7.5 mg of recombinant IFN-beta ser to 6 healthy volunteers. These IFN-induced metabolites, beta 2-microglobulin, and neopterin in serum, and 2',5'-oligoadenylate (2-5A) synthetase in peripheral blood mononuclear cells, are more sensitive to the presence of IFN than bioassay of IFN in serum. Up to 48 h after oral IFN was administered, serum IFN, beta 2-microglobulin, neopterin, or 2-5A synthetase were not generally increased compared to pretreatment levels, indicating that oral IFN had no significant biological effects. PMID- 1289409 TI - "Discordant" influence of equine recombinant interferon-beta 1 on the cytotoxic capacity of equine polymorphonuclear neutrophils and peripheral blood mononuclear cells in vitro and in vivo. AB - The influence of recombinant equine interferon-beta 1 (rEqIFN-beta 1) on mononuclear cells of peripheral blood (PBMC) and polymorphonuclear neutrophilic granulocytes (PMN) was tested under in vitro and ex vivo conditions. Treatment of equine PBMC with IFN in vitro enhanced the antibody-independent cytotoxicity (AICC) and antibody-dependent cytotoxicity (ADCC) while there was no significant effect on the cytotoxic capacity of PMN treated with rEqIFN-beta 1 in vitro. Ex vivo there was an increased capacity of AICC and ADCC upon single or multiple application of rEqIFN-beta 1 in PMN, only. Treatment with rEqIFN-beta 1 thus induced an increased cellular cytotoxicity in vitro and in vivo but in different populations of peripheral blood cells. In vivo rEqIFN-beta 1 causes a pronounced activation of PMN but not of PBMC as cytotoxic effector cells. This might be achieved indirectly, e.g., by cytokines produced by IFN-sensitive cells. PMID- 1289410 TI - Identification of a new interferon-alpha/beta-inducible DNA-binding protein that interacts with the regulatory element A of 2',5'-oligoadenylate synthetase ME-12 gene. AB - A new interferon (IFN)-stimulated response factor (ISRF) has been identified in nuclear extracts of IFN-alpha/beta-treated murine BALB/c-3T3 fibroblasts by the mobility-shift electrophoresis assay. The factor, ISRF-2, displays murine 2',5' oligoadenylate (2-5A) synthetase ME-12 gene 5' regulatory element A specificity and differs from the previously described IFN response element B-specific factor ISRF-1 in several aspects. ISRF-2 is restricted to the nucleus, whereas ISRF-1 exists in the cytoplasm and translocates into the nucleus upon treatment of cells with IFN-alpha/beta. The ionic strength requirement of ISRF-2 for maximal DNA binding activity is lower than that of ISRF-1. The DNA-binding activity of ISRF 2, but not that of ISRF-1, is markedly suppressed by Mg2+. In common with ISRF-1, the phosphorylated form of ISRF-2 appears to be required for DNA-binding activity. A model is proposed for the mechanism whereby murine IFN-alpha/beta regulates 2-5A synthetase ME-12 gene expression. PMID- 1289411 TI - Acid lability is not an intrinsic property of interferon-alpha induced by HIV infected cells. AB - Human immunodeficiency virus (HIV)-infected cells induce acid-labile interferon alpha (al-IFN-alpha) in cultures of mononuclear cells from peripheral human blood. We have investigated the physiochemical properties of such preparations to elucidate the reasons for acid-lability of this IFN. Al-IFN-alpha is a mixture of both glycosylated and unglycosylated molecules as shown by separation on Concanavalin-A Sepharose. Acid-lability is associated only with glycosylated molecules. Upon chromatography of the glycosylated fraction on Sepharose coupled to IFN-alpha-specific antibody, the portion of the IFN that is retained and eluted with guanidine-HCl is acid-stable, whereas the excluded antiviral activity is acid-labile, and is partially neutralized by antibodies to either IFN-alpha or IFN-gamma. Also, upon further purification of the unglycosylated fraction on the same antibody column, all antiviral activity remains indistinguishable from conventional IFN-alpha. Reconstitution experiments showed that glycosylated material excluded from the anti-IFN-alpha column potentiates antiviral activity of the IFN that is specifically retained by the column. This potentiation is abolished by acid treatment. Similar results are obtained with al-IFN-alpha from the serum of acquired immunodeficiency syndrome (AIDS) patients, indicating that its acid-lability is also the consequence of an acid-labile component that is capable of enhancing the antiviral activity. The potentiation of antiviral activity obtained by combining recombinant preparations of IFN-alpha and IFN gamma suggests that the cooperating molecule is IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289412 TI - Double-stranded RNA and interferon-alpha induce transcription through different molecular mechanisms. AB - Double-stranded (ds) RNA stimulates the synthesis of several mRNAs known to be induced by type I interferons (IFNs). In this report, it is shown that the IFN alpha stimulated genes (ISGs) 15, 54, 56, and GBP are transcriptionally induced by dsRNA. Transcriptional stimulation occurred in the presence of the protein synthesis inhibitor cycloheximide (CHX), indicating that inducibility was directly mediated by dsRNA through the action of preformed proteins. ISGF-3, the protein complex mediating primary transcriptional induction of ISGs by IFN-alpha, was not activated by dsRNA in the presence of CHX. Additionally, DNA-binding activity of ISGF-2/IRF-1, a protein involved in the regulation of the IFN-beta gene and ISGs, did not correlate with dsRNA-induced transcriptional induction of ISGs. This suggests that dsRNA and IFN-alpha induce ISGs through different molecular mechanisms. PMID- 1289413 TI - Phase II trials of interferons-alpha and -beta in advanced sarcomas. AB - Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha 2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c.t.i.w. In the second study, patients received IFN-beta ser 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta ser. Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha 2b and 17% of patients receiving IFN-beta ser. Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies. PMID- 1289414 TI - Oxidative stress. An early phenomenon characteristic of acute experimental pancreatitis. AB - Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were sacrificed at 1, 3, 6, and 24 h. Malondialdehyde and sulfhydryl groups concentration, as well as superoxide dismutase and catalase activity were measured in pancreatic, liver, and lung tissue. These parameters, with the exception of catalase, were also determined in serum and peritoneal exudate. Early and profound oxidative stress in each organ was evidenced by marked increases in malondialdehyde concentrations along with marked reductions in levels of sulfhydryl groups and superoxide dismutase; a paradoxical increase in catalase activity, perhaps compensatory, was noted in pancreas and lung. Survival for 24 h was associated with restoration of normality insofar as tissue malondialdehyde concentrations were concerned, but pancreas sulfhydryl groups remained markedly depleted. These data endorse the suggestion that the early provision of such compounds may help to accelerate recovery from hemorrhagic pancreatitis in humans. PMID- 1289415 TI - Intraoperative endoscopic electrohydraulic lithotripsy of pancreatic stones. AB - Two male patients with complications associated with chronic pancreatitis are described. In each patient, preoperative examinations revealed a large stone obstructing the main duct in the head of the pancreas. Lateral pancreaticojejunostomy was performed to relieve pain and prevent further attacks of pancreatitis. During each operation, the stone was fragmented under direct visual control with the use of a flexible choledochoscope and a contact electrohydraulic lithotriptor. The stone was removed and ductal flow through the head of the pancreas was reestablished. Our experience shows that endoscopic electrohydraulic lithotripsy facilitates operative removal of pancreatic stones deeply located in the head of the pancreas. PMID- 1289416 TI - Intraoperative ultrasonography in surgery for chronic pancreatitis. AB - We report our experience with intraoperative ultrasonography in 49 patients undergoing surgery for chronic pancreatitis. Among drainage procedures, there were 14 laterolateral pancreaticojejunostomies, 15 pseudocystojejunostomies, and 2 pseudocystoduodenostomies. Under the guidance of intraoperative ultrasonography, left sided partial resection of the pancreas was performed in 7 patients, whereas a Whipple-type procedure was necessary in 6 cases. All preoperatively diagnosed pseudocysts, abscess formations, and dilated pancreatic ductal systems could be easily localized with the assistance of intraoperative ultrasound. Additionally to diagnoses already made preoperatively, intraoperative ultrasonography revealed a second, smaller pseudocyst in one patient and pancreaticolithiasis in another case. However, significant assistance and comfort to the operating surgeon was provided in all cases by intraoperative ultrasound imaging. This technique, which is cost effective and minimally invasive, proved to be extremely helpful in localizing pancreatic fluid collections and the course of the pancreatic duct. It facilitates the operation by reducing tissue traumatization and operative time. In experienced hands, intraoperative ultrasonography is a reliable method and a useful adjunct to the surgeon. PMID- 1289417 TI - Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas. A phase I study. AB - This Phase I study was designed to build on the Gastrointestinal Tumor Study Group's experience with combined modality therapy in patients with pancreatic cancer. Thirteen patients with adenocarcinoma of the pancreas received weekly 5 fluorouracil by rapid intravenous infusion midway through a 2-h infusion of high dose leucovorin during external beam radiation therapy. Twelve patients received 100% of planned external beam radiation; treatment delays occurred in only three. Four patients received 100% of planned chemotherapy doses. Leukopenia and thrombocytopenia caused reduction of the number of chemotherapy doses given during radiation in six patients; diarrhea, severe nausea and vomiting, and wound abscess caused reduction in three patients. Ten patients were evaluable for response; two had complete responses, one had a partial response, and two had minor responses. In this small series baseline and post-treatment CA 19-9 levels predicted and correlated with response. We conclude that radiation and 5-FU modulated by leucovorin is a tolerable treatment regimen for carcinoma of the pancreas, with preliminary suggestion of activity, that warrants further Phase II testing. PMID- 1289418 TI - Human amniotic fluid obtained from diabetic women. A potent stimulator of islet cell replication. AB - Recently, human amniotic fluid (HAF) from healthy women was found to stimulate growth and function of pancreatic B-cells. Here, the effect of HAF and serum from healthy probands (HS) was compared with that from probands with gestational (GD), noninsulin-dependent (NIDDM), or insulin-dependent diabetes (IDDM) on islet function and replication. Rat islets were cultured in the presence of either HAF or HS for 7 d. Insulin content and basal insulin release were not different after exposure of the islets to HAF or HS from healthy or diabetic women. In contrast to HS, HAF provoked the islets to deliver significantly more insulin during culture. Additionally, the same islets exhibited a more intense response to a glucose challenge. The degree of HAF-induced insulin release was not influenced by the type of diabetes. HAF and HS from GD and NIDDM women did not influence the islet DNA synthesis in comparison to HAF and HS from healthy pregnant women. However, HAF but not HS from IDDM pregnant women, elicited a significant increase in islet replication. Most effective in stimulating islet cell replication were HAFs from IDDM pregnant women belonging to the White D-type. It was shown that the relatively high concentration of insulin in the HAFs was not directly responsible for the observed increase of the islet DNA synthesis. HAF from women with long-term diabetes is supposed to contain factor(s) that might directly or indirectly enhance islet replication. PMID- 1289419 TI - Determination of pancreatic lipase by immunoactivation technology. A rapid test system with high sensitivity and specificity. AB - This paper describes the test characteristics and clinical relevance of a newly developed homogeneous enzyme immunoassay IMAC lipase test for the determination of serum pancreatic lipase. The method of determination is based on an immunoactivation technology and utilizes antibody fragments against human pancreatic lipase covalently bound to the marker enzyme horseradish peroxidase. The serum samples of 408 persons were investigated with this new assay. The within-run and day-to-day precision, the linearity, and the recovery of this immunoassay correspond to a very high degree to the requirements made of a modern immunological test. Comparison with an ELISA method resulted in a correlation coefficient of 0.971, whereby the IMAC lipase assay tended to register lower serum values. The serum range for the IMAC lipase test is 0-47 micrograms/L, based on a normal collective of 187 healthy controls. A sensitivity of 95.8% for the diagnosis of acute pancreatitis at a cutoff level of twice the upper normal range and a specificity of 99.3% at an efficiency of 99.8% can be given. The advantage of the IMAC lipase test method is its ability to be adapted to work on automatic laboratory analyzers. PMID- 1289420 TI - Expression of the human MUC1 mucin cDNA in a hamster pancreatic tumor cell line HP-1. AB - A full length cDNA for the human mucin gene, MUC1, under the control of human beta actin promoter, was transfected into a carcinogen induced hamster pancreatic ductal tumor cell line, HP-1. Transfectants were selected by resistance to geneticin. Integration of the foreign human MUC1 cDNA occurred at multiple sites in the genome of HP-1. Northern blot analysis showed MUC1 expression in cells transfected with MUC1 cDNA placed in the correct orientation, but not in control cells (HP-1 cells transfected with vector alone, or with the MUC1 cDNA placed in the antisense orientation). Western blot analysis using monoclonal antibody HMFG 2, which is reactive with the MUC1 protein, showed results consistent with the Northern blot data. Positive immunoperoxidase staining using HMFG-2 was seen in HP-1 cells transfected with MUC1 cDNA but not with untransfected or HP-1 control cells. The integration of human MUC1 mucin gene in HP-1 cells caused no significant change in the growth rate of HP-1 cells in vitro, but resulted in an enhanced growth rate for xenografts of MUC1 transfected HP-1 cells grown in nude mice. PMID- 1289422 TI - Pancreatic carcinoma associated with chronic calcifying pancreatitis. AB - A total of 160 Japanese patients with pancreatic carcinoma were treated in the Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan, from January 1976 to December 1991. Four of these patients had an accompanying pancreatic calcification with a 2.5% incidence of pancreatic carcinoma. Those four patients consisted of 52, 75, 75, and 82 year-old men. Three complained of jaundice and another developed an abdominal mass. Two of the four patients were diabetic and had a past history of heavy alcoholic intake. Three pancreatic carcinomas were located in the head of the pancreas, including two with multiple small calcifications in the entire pancreas and one with a solitary large calcification in the head. Another pancreas body carcinoma was associated with diffuse small calcifications both in and distal to the mass. In three pancreatic carcinomas, pancreatic calcification was demonstrated proximal and distal to the pancreatic carcinomas. All four patients died within 14 months after the clinical diagnosis of pancreatic carcinoma. Although we cannot draw a definitive conclusion on the link because of the limited number of cases in this retrospective study, followup studies on patients with chronic calcifying pancreatitis are needed for clarification. PMID- 1289421 TI - Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction. AB - We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction. PMID- 1289423 TI - Acinar cell carcinoma of the pancreas. Report of two cases with complex histomorphologic features causing diagnostic problems. AB - Two pancreatic acinar cell carcinomas with distinctive morphologic features are described. Both tumors showed a variable combination of different histomorphologic patterns formed by tumor cells in different degrees of acinar differentiation. They caused diagnostic problems involving differential diagnosis from normal pancreas and from mixed acinar-endocrine tumor. The presence of mitosis, nuclear atypia, and tumor necrosis are helpful for recognizing its neoplastic nature, and the ultrastructural finding of zymogen-like but not neurosecretory granules prevented the misdiagnosis of a mixed acinar-endocrine tumor. Immunohistochemical studies revealed variable immunostaining patterns corresponding to different types of tumor cell present. Both tumors were found to be aneuploid by flow cytometric DNA study. Our study confirmed previous observations that pancreatic acinar cell carcinomas are highly malignant tumors in spite of the fact that they can differentiate into highly differentiated acinar cells. PMID- 1289424 TI - Adenocarcinoma of the pancreas coexisting with pancreatic abscess. AB - Of 20 patients treated for pancreatic abscess during the years 1984-1991, two patients were found to have adenocarcinoma of the pancreas associated with their pancreatic abscesses. In one patient an adenocarcinoma of the proximal pancreas caused ductal obstruction, which may have been the primary cause of an abscess distal to the tumor. In the second patient, metastatic adenocarcinoma of the pancreas and a concurrent pancreatic abscess were found when the patient's abdomen was explored for complications related to gallstone pancreatitis. In both patients, the tumor was unresectable at presentation. A detailed review of these cases is presented as well as a review of the related literature. PMID- 1289425 TI - Acute pancreatitis associated with milk allergy. AB - We are reporting the case of a 23-yr-old patient who had recurring episodes of acute pancreatitis characterized by the typical abdominal pain, elevated serum levels of pancreatic enzymes, and enlargement of the pancreas and edema on sonogram. These episodes were accompanied by facial erythema with conjunctival injection, generalized pruritus, diarrhea, and eosinophilia, and they were induced by the consumption of milk. The serum levels of IgE specific to cow milk proteins and to beta-lactoglobulin were increased. We suggest that these episodes are caused by a milk allergy (milk), that has been described as an unusual cause of acute pancreatitis. PMID- 1289426 TI - Time period of immobility and pressure ulcer development in spinal cord-injured patients. PMID- 1289427 TI - Factors associated with closed head injury in a pediatric population. AB - The purpose of this study was to identify characteristic factors in children who sustained closed head injury (CHI) between birth and less than 15 years of age. A two-year retrospective audit of charts from a large metropolitan pediatric hospital with a trauma center yielded a sample of 138 charts that met the established criteria for inclusion in the study. Using a descriptive design, data were gathered on age, sex, race, cause of injury, severity of injury, season of accident, time of accident and length of hospital stay. Data analysis revealed that males were 1.5 times more likely to sustain CHI than females. Both sexes showed the highest incidence of CHI during the first year with a second less dramatic peak at around 6 years of age. Transportation-related causes accounted for 57.2% of the injuries with falls accounting for another 22.5%. Of the transportation-related injuries, 27.5% were associated with motor vehicle accidents. The lack of restraint use for subjects in the motor vehicle accident group was associated with 5 deaths as opposed to no deaths in subjects who were restrained. Over 70% of the injuries occurred in the time periods of 2:00-6:00 p.m. (31.9%) and 6:00-10:00 p.m. (40.7%). CHI occurred less frequently in the winter (13.8%) than any other season. Using the Glasgow Coma Scale scores, 56.5% of the injuries were categorized as mild, 17.4% were moderate and 26.1% were severe. There was an 8% mortality rate secondary to injury in the sample. PMID- 1289428 TI - Traumatic brain injury: a family experience. AB - Traumatic brain injury (TBI), sometimes referred to as a silent epidemic, affects thousands of people each year. A head injury not only affects the patient, but the entire family system as well. Families experience a myriad of needs during this time of crisis. With the immediate focus on the patient's physical or cognitive state, the family's needs may go unnoticed or unrecognized. It is imperative health care professionals understand the emotional impact on family needs, and the unique grieving patterns which influence their ability to cope with this situation. Caregivers are advised to assess, formulate and implement a plan of care for the family as well as the patient. Since families play such an integral role in the patient's recovery process, it is crucial to recognize the scope of the TBI experience and provide care within the context of the individual family system. PMID- 1289429 TI - Head injury: impact on the wives. AB - Wives of head-injured patients often need considerable support because of the myriad of role transitions and role changes they experience. The impact of the head injury on the wife of a survivor is presented in this article. Content analysis was used to analyze data with the themes of role changes, emotional impact of the injury, hope and need for support emerging. Implications for practice and research include need for support groups with nurses as facilitators, the importance of fostering hope, and need for education of health care professionals. PMID- 1289430 TI - Occupational stress in neurosurgery: an exploratory study. AB - Occupational stress in nursing has been a popular topic for investigation. In particular, comparisons between practice areas such as the intensive care unit (ICU) and medical-surgical unit have attempted to identify what factors are stressful, and whether some nursing environments are more stressful than others. Such studies have led to inconclusive findings. While many practice areas have been studied, the neurosurgical ICU and neuromedical/neurosurgical units have largely been overlooked. Using interviews, this exploratory study examined aspects of nursing perceived as stressful by staff members working in ICU and medical-surgical units in a neuroscience center. Findings suggested that patient care, communication, workload, management and supervision, organizational and personal circumstances are major sources of stress. These findings are in keeping with studies of stress conducted in national and international non-neurosurgical nursing practice areas. PMID- 1289431 TI - Chronobiological aspects of epileptic phenomena: a literature review, implications for nursing and suggestions for research. AB - Every physiologic and psychologic variable studied heretofore demonstrates rhythmic fluctuations. Chronobiology is the field of study which examines these fluctuations. Chronobiology is highly significant to nursing practice, since human responses are affected by these rhythmic fluctuations. A review of the literature produced little information on epilepsy chronobiology. The status of research in epilepsy chronobiology remains at the basic science level. Continued research is a priority before nursing can use epilepsy chronobiology knowledge in the clinical setting. PMID- 1289432 TI - Purple glove syndrome: a complication of intravenous phenytoin. AB - Intravenous phenytoin, available for use since 1956, has several well known adverse effects, such as hypotension, arrhythmias and toxicity. Purple glove syndrome is a less common complication that can have serious consequences. Fasciotomies, amputations and permanent disuse of the hand and forearm have been reported. The etiology of purple glove syndrome is still unknown, but possible etiologies and risk factors have been suggested. Three stages of purple glove syndrome have been identified: appearance, progression and resolution. During the second stage, progression, purple glove syndrome can be identified as either mild or severe. Mild cases may heal uneventfully when nursing measures such as elevation, application of dry, gentle heat and measures to prevent secondary injury are instituted. Severe cases may require emergency surgical intervention such as fasciotomy to relieve pressure and restore blood flow. Therapeutic nursing interventions aimed at maximizing healing and promoting comfort are essential. PMID- 1289433 TI - Powerlessness and the patient under neuromuscular blockade. AB - The patient under neuromuscular blockade is dependent on members of the interdisciplinary team for all physical and psychological needs. Loss of control leads to feelings of powerlessness and helplessness which can adversely affect the patient's ability to cope. The nurse caring for this patient must be able to effectively combine clinical expertise with compassion in order to most effectively help the patient cope with the period of powerlessness. An individualized approach to restore control helps curtail the progression of powerlessness to hopelessness and limit the associated depression and anxiety. PMID- 1289434 TI - The evaluation of self-report instruments for use in research. PMID- 1289435 TI - Clinical applications of brain death protocols. AB - The declaration of death by neurological criteria has become more commonly accepted and used within the medical community, especially within the past 10 years. There remains, however, a great deal of misunderstanding and lack of awareness among health care professionals as to the criteria used to determine brain death and the importance of adhering to brain death determination protocols. Youngner et al, in their 1989 survey, found more than one-third of surveyed physicians involved in the decision-making process for brain death were still unable to correctly identify and apply the whole brain criteria needed to determine brain death. To some degree, this unfamiliarity can perhaps be explained by the infrequency with which brain death occurs. Physicians and nurses are usually not involved in brain death pronouncements more than a few times each year. Because of this, hospitals need to develop and maintain brain death protocols which are in keeping with the most current scientific literature and accepted medical practice. PMID- 1289436 TI - The design and implementation of a neuroscience nursing program. PMID- 1289437 TI - [Present status and clinical therapy of pancreatic diseases]. PMID- 1289438 TI - [Etiology and physiopathology of acute pancreatitis]. PMID- 1289439 TI - [Image diagnosis of acute pancreatitis]. PMID- 1289440 TI - [Treatment of acute pancreatitis]. PMID- 1289441 TI - [Etiology and physiopathology of chronic pancreatitis]. PMID- 1289443 TI - [Non-invasive therapy of pancreatic pseudocyst]. PMID- 1289442 TI - [Diagnostic imaging of chronic pancreatitis]. PMID- 1289444 TI - [ESWL therapy of pancreatic calculi]. PMID- 1289445 TI - [Endoscopic therapy of chronic pancreatitis]. PMID- 1289446 TI - [Diagnostic imaging of pancreatic neoplasms by CT, MRI and US]. PMID- 1289447 TI - [Surgical therapy and prognosis of pancreatic neoplasms]. PMID- 1289448 TI - [Diagnosis of pancreatic cystic tumor]. PMID- 1289449 TI - [Therapy of pancreatic cystic tumors]. PMID- 1289450 TI - [Diagnosis of pancreatic diseases by endoscopic ultrasonography]. PMID- 1289451 TI - [A case of acquired primary sideroblastic anemia treated with vitamin B6]. PMID- 1289452 TI - [A case of ALL with Candida liver abscess treated with amphotericin B through portal vein]. PMID- 1289453 TI - [A difficult diagnostic case of small intestinal diverticulum with ulcer]. PMID- 1289454 TI - [Two cases of severe liver injuries induced by acetaminophen]. PMID- 1289455 TI - [Relationship between viral hepatitis and alcoholic liver disease]. PMID- 1289456 TI - [Sick building syndrome]. PMID- 1289457 TI - Risk management tips for dentists. PMID- 1289458 TI - Dental office recordkeeping requirements under the MOSH/OSHA bloodborne pathogens standard. PMID- 1289459 TI - Income protection--protecting your greatest asset. PMID- 1289460 TI - Hiring and keeping good people--a guide to office organization. Part 1. Creating Direction. PMID- 1289461 TI - DDS: the head of the class in 1991. PMID- 1289462 TI - A clinico-pathologic presentation. Unicystic Ameloblastoma. PMID- 1289463 TI - What is the ADA doing for the young dentist? PMID- 1289464 TI - Surviving the challenges of starting your practice from scratch. PMID- 1289465 TI - Identifying legal pitfalls for the young dentist. PMID- 1289466 TI - Expert systems and expert behavior. AB - Iliad 4.0 and QMR 2.03 are computer-based diagnostic knowledge bases that can play many roles in decision support and other areas of medical practice, but neither appears ready to assume the role of an expert diagnostic consultant. In contrast to human experts, these programs have problems related to recognition of their own limitations, interpretation of continuous data, recognition of dependent findings, selection of tests, and description of the impact of certain tests. Suggestions to improve these aspects of knowledge bases are offered. PMID- 1289467 TI - Computer-assisted test interpretation: considerations in patient care. AB - Computer-assisted test interpretation (CATI) is a set of developing technologies designed to support medical decision-making. This paper develops a taxonomy of computer-assisted test interpretation, giving specific consideration to the characteristics of the data that are to be interpreted, the nature of the interpretive task, the expected involvement of the health professional in the generation of the interpretation, the inference mechanism used for the interpretation, and the broader context of the interpretation. We go on to examine potential benefits and disadvantages of CATI systems in terms of accuracy, information management, interpretation time, patient management, medical communication, and expense. Finally, we examine electrocardiogram interpretation systems from the perspective of this taxonomy, and offer suggestions regarding areas of further inquiry into the effects of CATI on medical care. PMID- 1289468 TI - Regional variation in VAMC's operative efficiency. AB - The Department of Veterans Affairs is managed by a global budget regulated by Congress. How effective the VA handles this budget can provide insight into future plans for any form of universal health insurance. Using Date Envelope Analysis (DEA) this study shows that 51 of 158 continental VAMCs operate relatively efficiently. Variation in operative efficiency could be explained by Service Area size and geographic regional location. This finding suggests more active regional planning may improve veteran hospital operative efficiency. PMID- 1289469 TI - Using an artificial neural network to diagnose hepatic masses. AB - Using abdominal ultrasonographic data and laboratory tests, radiologists often find differential diagnoses of hepatic masses difficult. A computerized second opinion would be especially helpful for clinicians in diagnosing liver cancer because of the difficulty of such diagnoses. A back-propagation neural network was designed to diagnose five classifications of hepatic masses: hepatoma, metastatic carcinoma, abscess, cavernous hemangioma, and cirrhosis. The network input consisted of 35 numbers per patient case that represented ultrasonographic data and laboratory tests. The network architecture had 35 elements in the input layer, two hidden layers of 35 elements each, and 5 elements in the output layer. After being trained to a learning tolerance of 1%, the network classified hepatic masses correctly in 48 of 64 cases. An accuracy of 75% is higher than the 50% scored by the average radiology resident in training but lower than the 90% scored by the typical board-certified radiologist. When sufficiently sophisticated, a neural network may significantly improve the analysis of hepatic mass radiographs. PMID- 1289470 TI - Development of a diagnostic and therapeutic simulation system based on patient data and specialist's knowledge. I. Simulation of diagnostic process. AB - A new simulation system of diagnostic and therapeutic processes is developed. The aim is to train medical students for the practical use of their knowledge, utilizing patient data in a total hospital information system. The knowledge in the system is presented by the specialists for every case. In medical school there are many specialists in various fields. With their cooperation the system can grow up to a comprehensive CAI system for clinical education. The system is designed to work on the mainframe for easiness of development, maintenance and extensions of the system. The present framework has been applied to the simulation of diagnostic process. The usefulness of the present system has been confirmed by specialists and students. PMID- 1289471 TI - Microleakage--full crowns and the dental pulp. AB - Recent studies have described microleakage under full crowns cemented with several different cements. This study tested three different types of crown margin preparations--a chamfer, a shoulder, and a shoulder plus a bevel to determine whether or not the margin preparation could affect microleakage. All crowns were cemented with zinc phosphate cement. The crowns were tested for leakage in thermocycled dye. All crowns demonstrated significant leakage following the path of the dentinal tubules into the pulp. This could possibly be one of the causes of pulpal inflammation and even pulpal death under full crowns. PMID- 1289472 TI - Cervical canal leakage after internal bleaching. AB - The effects that walking bleach procedures had on root canal filling leakage and the extent of dentinal penetration were studied. Forty teeth were divided into four groups: 1--GP, set sealer, no base; 2--GP, set sealer, 2-mm Cavit base; 3- GP, unset sealer, no base; and 4--GP, unset sealer, 2-mm Cavit base. All were bleached for 7 days, fresh bleach was added for another 7 days, then methylene blue dye was placed for 5 days. The extent of dye penetration apically along the root canal filling and through the dentinal tubules was evaluated. The results indicate that 2 mm of Cavit was sufficient to significantly reduce linear leakage and dentinal penetration. The Cavit should be placed to a level slightly coronal to the facial cementoenamel junction. Teeth with cemental defects demonstrated greater perpendicular dye penetration in the areas of the defects than those with intact cementum. The data from this study suggest the use of a base material over gutta-percha in clinical practice prior to internal walking bleach procedures. PMID- 1289473 TI - Leaching of hydrogen peroxide from bleached bovine enamel. AB - Accurately weighed bovine enamel slabs were individually immersed in 2 ml of 35% hydrogen peroxide for 1, 3, 5, 30, or 60 min. A control group was obtained by individual immersion of bovine enamel slabs in 2 ml of saline for 60 min. All samples were washed, dried, acid-etched with 37% phosphoric acid for 60 s, then washed and dried again. Two milliliters of double-distilled water were used for individual sample leaching. Leaching was done for 1, 5, 10, 20 min, or 7 days for the experimental groups and for 7 days for the control group. The samples of one of the experimental groups were leached for a second time for 1 min. A total of 112 samples was used in this study. Hydrogen peroxide was spectrophotometrically identified and quantified in all leaching solutions based on the oxidation reaction of leuco-crystal violet buffer solution by hydrogen peroxide, a reaction catalyzed by horseradish peroxidase. The results revealed a significant difference in the quantity of leached peroxide between bleached samples (irrespective of the duration of leaching) and control, saline-treated ones. No difference was observed in the quantity of leached peroxide between releached samples and control, saline-treated ones. However, these were small, random, and numerically insignificant. Statistically significant differences were also noted among some of the experimental groups. They were thought to hold no clinical significance. The results suggested that upon immersion, the complete leaching of peroxide from bleached enamel occurs rapidly. PMID- 1289474 TI - Effect of different endodontic treatment protocols on periodontal repair and root resorption of replanted dog teeth. AB - This study examined, histologically, the healing of intentionally damaged root surfaces of replanted teeth with either uninfected or infected root canals treated with short- and long-term calcium hydroxide. Thirty beagle dog incisors were randomly divided into four groups. In group 1, uninfected obturated incisors were extracted, the roots were longitudinally grooved and the teeth were replanted within 2 min. In group 2 the root canals were artificially infected followed by extraction, longitudinal grooving, and replantation as described in group 1. Fourteen days after replantation, the root canals were fully instrumented and medicated with intracanal calcium hydroxide. One week later the root canals were permanently obturated with gutta-percha and sealer. The teeth in group 3 were treated as described in group 2 but after 1 wk the calcium hydroxide dressing was repacked for the duration of the study. In group 4 (positive control) the teeth were treated as described in groups 2 and 3 but no endodontic treatment was performed. After 8 wk, sacrifice and histological preparation were carried out. In group 1 complete cemental repair was seen in all teeth. In groups 2 and 3, complete and incomplete cemental repair was seen in seven and two teeth, respectively. An ankylotic area was present in one tooth in group 3. None of the teeth in group 4 showed cemental repair. It was concluded that short- and long term calcium hydroxide treatment resulted in similar healing patterns when endodontic treatment is initiated 14 days after replantation of teeth. PMID- 1289475 TI - Endotoxin and gram-negative bacteria in the rat periapical lesions. AB - The purpose of this study was to measure the amount of endotoxin as well as to identify Gram-negative bacteria in experimental periapical lesions in rats. Molar pulps were exposed and infected and the amount of endotoxin in the periapical tissue of the right mandibular first molar was measured by Endospecy, while the colony number of Gram-negative bacteria was determined in the same region of the left mandibular first molar. In the control animals, the amount of endotoxin in the periapical tissues did not change at all during the experimental period, and no Gram-negative bacteria were isolated. In the experimental animals, the amount of endotoxin in the periapical tissues increased gradually from 1 to 70 days, and its level was significantly greater than that of control animals after 7 days. Gram-negative bacteria were isolated from the periapical tissues and their number gradually increased from 1 to 14 days (26 to 82%), but decreased at 21 days. It was approximately 60% from 28 to 70 days. The results of this study showed that the amount of endotoxin in the periapical tissues gradually increased with increasing time and that Gram-negative bacteria were isolated from the same region but did not increase in number concurrently with the increase in the amount of endotoxin. PMID- 1289476 TI - Root canal configuration of the mandibular first premolar. AB - One hundred six human mandibular left and right first premolars, previously extracted due to nonrestorable caries, periodontal disease, or orthodontic reasons, were sectioned perpendicular to the long axis of the root starting at the cementoenamel junction. Three-millimeter sections were made with an ultrathin separating disc to the level of the anatomical apex. After 1 day in 5.25% NaOCl, each section was rinsed in phosphate-buffered saline, evaluated with a stereomicroscope, and photographed. The slides were projected and the shape of the canal, incidence of multiple canals, level of bifurcation, and any other variant anatomy were recorded. Seventy-six percent of the premolars demonstrated Type I canals and 24% contained Type IV. The shape of the canals was predominantly oval or round. An interesting finding was the number of C-shaped canals which were associated predominantly with Type IV canal systems. This occurred in 14% of the roots. PMID- 1289477 TI - Incidence of interappointment emergency associated with endodontic therapy. AB - Endodontic interappointment emergency (EIE) occurs in a low incidence following treatment by qualified operators. The purpose of this study was to assess the incidence of EIE after treatment by undergraduate students and to examine its correlation with preoperative and operative parameters. Randomly selected 334 records were retrospectively surveyed for unscheduled emergency appointments following endodontic treatment by undergraduate students. Treatment included step back canal preparation in multiple visits with formocresol interappointment dressing. The incidence of EIE was 4.2%, and unrelated to the patients' sex and age or to tooth location. It was significantly higher in nonvital than in vital teeth (p < 0.05), with the highest occurrence in nonvital teeth unassociated with periapical radiolucency. Clinically, EIE was associated with swelling in half of the cases. It is concluded that the incidence of EIE following treatment by undergraduate students is low and related to tooth vitality. PMID- 1289478 TI - Modified endodontics for lengthy canals. AB - A review of the dental literature concerning lengths of maxillary cuspids and reports of cuspid gigantism are presented. Endodontic therapy in these cases requires variations and modifications in conventional therapy for successful treatment. A case report is presented which illustrates some of these treatment modifications. PMID- 1289479 TI - Symmetrical pulp obliteration in mandibular first molars. AB - Pulp obliteration is an extremely rare morphological type of pulp calcification, with calcified material completely occupying the pulp chamber and root canal spaces. The etiology of pulp obliteration may be trauma or systemic diseases such as secondary hyperparathyroidism. Pulp obliteration may also be seen in dental anomalies such as dentinogenesis imperfecta and dentinal dysplasia. In cases of pulp obliteration with periapical disease, the preferred treatment is surgery, while calcified canals without symptoms or periapical lesions are best left untreated. PMID- 1289481 TI - Trigeminal neuralgia--a dental diagnosis challenge. PMID- 1289480 TI - Using cyanoacrylate to facilitate rubber dam isolation of teeth. AB - Cyanoacrylate is an extremely strong bonding agent which has many applications in medicine. It is also effective in obtaining a leakproof seal of rubber dam around a structurally compromised tooth requiring endodontic therapy. PMID- 1289482 TI - Infectious or not? The handpiece controversy. PMID- 1289483 TI - An open letter on the handpiece issue. PMID- 1289484 TI - OSHA--an agency run amok. PMID- 1289485 TI - Life in Oregon--1893. PMID- 1289486 TI - Managed care: the values squeeze. PMID- 1289487 TI - Coping with the cost of infection control. PMID- 1289488 TI - Chronic oral mucositis--a clinicopathologic conference. PMID- 1289489 TI - CDEM survey results--the verdict is in. PMID- 1289490 TI - [Stability of dilute solutions of ganciclovir sodium (Cymevan) in polypropylene syringes and PVC perfusion bags]. AB - The stability of ganciclovir sodium solutions stored in polypropylene syringes and PVC bags was tested in 0.9% sodium chloride at three concentrations 70, 200 and 350 mg/50 ml for polypropylene syringes, and two concentrations (70 and 350 mg/250 ml) for PVC bags and at three temperatures (-20 degrees C, + 4 degrees C, room temperature). The solutions, which had been initially frozen, were thawed by exposure to microwave radiations. The stability of each sample was determined by high-performance liquid chromatography. The results of this study indicate that admixtures of ganciclovir sodium at the concentration rates tested can be frozen for at least one year and are stable for at least 80 days at + 4 degrees C and 7 days at room temperature. PMID- 1289491 TI - Flow cytometry to evaluate the parasitemia of Plasmodium falciparum. AB - The resistance of plasmodiums to the current antimalarial agents has spurred the search for new active molecules of vegetal origin or chemical synthesis. The screening of antimalarial molecules "in vitro" was done by simple but tedious techniques such as quantification of parasitemia through optical microscopy or by using radioactive markers. We have developed a new method to evaluate parasitemia by using the ODAM ATC 3000 flow cytometer and biological cell sorter. We selected the ethidium bromide for labelling the nucleic acids of Plasmodium falciparum, and we optimised the method by using a mathematical model: the design of Hadamar. This simple technique presents the advantage of being an objective and rapid count of large number of red cells (10(6) x 10(7)). This method is rapid, reliable, reproducible, devoid of subjectivity and provides more precise results than those of optical microscopy. The good correlation between paraitemia measured by optical microscopy and fluorescence obtained by flow cytometry allows us to recommend this technic for the screening of new antimalarial molecules. PMID- 1289493 TI - [Clinical formulations of amphotericin B]. AB - The clinical use of amphotericin B is impaired by its poor water solubility and by the severity of its side effects. Several amphotericin B formulations have already been prepared in an attempt to overcome these disadvantages. The following methods have been proposed to solubilize amphotericin B in water: the complexation of amphotericin B with metallic ions, sodium tetraborate or gamma cyclodextrin or the synthesis of semi-synthetic derivatives. Another approach was to use a carrier (liposomes, lipoproteins, emulsions or surfactants) to target amphotericin B. This paper summarizes and criticizes these formulations. PMID- 1289494 TI - [Reactions and interactions of drugs]. PMID- 1289492 TI - [Freezing of solutions for parenteral usage: advantages and disadvantages. Nine month's experience at the pharmacy of the Hospital of Nancy]. AB - Usually parenteral solutions can be kept longer if they are frozen. This freezing procedure assumes one knows the stability of frozen drugs. Freezing has a few drawbacks; preparations must be labelled twice (before and after freezing), only standardized doses can be prepared, thawing procedures must be established, cost of freezer and microwave-oven and time needed for thawing and labelling. There are four main advantages; production plannings are improved because time needed for preparation is reduced, quality assurance of the preparation, availability of preparation at any time, reduce of drug wastage. Freezable drugs are listed and sorted by pharmacological class. The presentation includes drug concentration, vehicle, container, storage temperature, assay procedure and stability. Our nine months experience is presented. Three drugs are frozen; methotrexate, metoclopramide and ganciclovir. Considerable preparation time is saved and economy is about FF 150,000. PMID- 1289495 TI - Disulfide bond cleavage of human fibrinogen by cis-diamminedichloroplatinum(II). AB - Disulfide bridges in fibrinogen (Fbg) were cleaved by cis diamminedichloroplatinum(II) (cis-DDP). Incubation with 120 molar excess of cis DDP at pH 7.4 and 37 degrees C in the presence of EDTA resulted in cleavage of seven disulfide bridges out of 29. In the presence of calcium, however, the number of cleavages were reduced to four. The result indicates that calcium, which has three high affinity sites on Fbg, protects disulfide bridges from the rupture. Thrombin clottability was examined by turbidity measurement. The cis-DDP treated Fbg was shown to give a decreased fiber thickness. As the cleavage proceeded, the clotting ability of Fbg decreased. PMID- 1289496 TI - Cytokine-related immunopotentiating activities of paramylon, a beta-(1-->3)-D glucan from Euglena gracilis. AB - Paramylon, a beta-(1-->3)-D-glucan, isolated from Euglena gracilis, was tested for its adjuvant activity on the antibody response to sheep red blood cell (SRBC) in mice. Paramylon markedly enhanced anti-SRBC plaque-forming cell production at a dose of 10 mg/kg. It was also found that in vitro addition of lipopolysaccharide in culture to macrophages from paramylon-treated mice produced a large amount of interleukin 1 (IL-1) and there was a significant level of interleukin 6 (IL-6) induced transiently in the blood of these mice. As IL-1 and IL-6 play crucial roles in the immune response to T cell-dependent antigens like SRBC, the immunopotentiating effect of paramylon might be expressed through the action of these cytokines. PMID- 1289497 TI - Comparison of the effects of halothane and propranolol on the effective refractory period and the ventricular activation in a canine myocardial infarction model. AB - The effects of halothane on the effective refractory period (ERP) and the ventricular activation were examined in a canine myocardial infarction model, and compared with those of propranolol. Halothane reduced the heart rate and prolonged the ERP in both normal and infarcted zones. A prolongation of ERP with halothane was also observed during atrial pacing at the same rate as in control, but the effect was less than during sinus rhythm. Halothane (1 MAC) further delayed or blocked the delayed activation in the infarcted zones with only slight effects on the activation of the normal zones. Propranolol (0.2 mg/kg) prolonged ERP during sinus rhythm, but it did not affect either the ERP or ventricular activation during atrial pacing. In conclusion, halothane produced a selective depression of the delayed activation and the prolongation of ERP, which may be caused by both direct effects on the myocardium and secondary effects such as a reduction of the heart rate. These effects of halothane may contribute to its antiarrhythmic effects in the myocardial infarction model which have been previously reported. PMID- 1289498 TI - Pharmacokinetic interaction of zonisamide in rats. Effect of other antiepileptics on zonisamide. AB - The pharmacokinetics of zonisamide (ZNS) and the effects of phenobarbital (PB), valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) on ZNS kinetics were investigated in rats. The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS. ZNS showed a linear disposition kinetics after oral administration of ZNS within the dose examined. Moreover, the pharmacokinetic behaviors of ZNS were not altered after multiple dosing. The decreased t1/2 value of ZNS by PB or CBZ pretreatment and the increased Vd/F value of ZNS by VPA pretreatment were observed, although it showed no marked effect of PHT on ZNS kinetics. The enhanced metabolism of ZNS was observed by PB or CBZ pretreatment from an in vitro metabolism study. The serum protein binding and erythrocyte distribution of ZNS showed no significant change in the presence of other antiepileptics in vitro. These results indicate that the decreased t1/2 value of ZNS is attributable to the enzyme inducing effect of PB or CBZ, and that neither protein binding nor erythrocyte distribution of ZNS could be the reason for the increased Vd/F value of ZNS by VPA coadministration. PMID- 1289499 TI - Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1 benzopyran-4-one (T-614), a novel antiinflammatory agent. 3rd communication: the involvement of bradykinin in its analgesic actions. AB - In order to elucidate the analgesic mechanism of 3-formylamino-7 methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614), its effects on the kinin-forming system were examined both in vivo and in vitro. T-614, at doses more than 10 mg/kg p.o., exhibited a significant inhibitory effect on the increased levels of bradykinin released into the pouch fluid of kaolin-induced inflammation in rats. In the kaolin-induced writhing response in mice, which is shown to be mainly dependent on the action of bradykinin, T-614 reduced not only the writhing frequency but also the peritoneal levels of bradykinin in a dose dependent manner. Whereas, in the zymosan-induced writhing response in which prostaglandin I2 (PGI2) is shown to be an important mediator, it did not exert an obvious inhibition on either writhing responses or peritoneal PGI2 levels at a highest dose of 100 mg/kg. T-614 did not inhibit the activities of serine proteases, such as trypsin, thrombin, kallikrein and plasmin. Furthermore, it did not affect the kinin-forming enzymes of rat plasma in vitro. The above results suggest that the analgesic effects of T-614 may be partly mediated by the inhibition of bradykinin release in the local inflamed tissue. PMID- 1289500 TI - Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1 benzopyran-4-one (T-614), a novel antiinflammatory agent. 4th communication: inhibitory effect on the production of interleukin-1 and interleukin-6. AB - In vitro effects of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran 4-on e (T-614), a novel antiinflammatory compound, on the production of interleukin-1 (IL-1) and/or interleukin-6 (IL-6) by human monocytes and the THP-1 cells of a human monocytic cell line, were examined. T-614 inhibited the release of immunoreactive IL-1 beta from these cells stimulated with lipopolysaccharides (LPS) in a dose-dependent manner (0.3-30 micrograms/ml). The release of IL-6 from THP-1 cells, as determined by the assays for its hepatocyte-stimulating activities and immunoreactivities, was inhibited by T-614 with the IC50 values of 2.0 and 6.6 micrograms/ml, respectively. Northern blotting analysis using LPS stimulated THP-1 cells indicated that the inhibitory effect of T-614 on IL-1 beta production is caused by the suppression of IL-1 beta mRNA expression. The inhibition of cytokine production by T-614 may provide an important insight into the additional mechanisms contributing to its antiinflammatory activities. PMID- 1289501 TI - Effects of long-term administration of (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1 ethoxycarbonyl-3- phenylpropyl)amino]propionyl]-2-oxoimidazolidine-4-carboxylic acid hydrochloride (TA-6366), a new angiotensin I converting enzyme (ACE) inhibitor, from the pre-hypertensive stage on morphological change and mechanical property related to sodium ion permeability in aorta of spontaneously hypertensive rats (SHRs). AB - Effects of (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3 phenylpropyl)amino]- propionyl]-2-oxoimidazolidine-4-carboxylic acid hydrochloride (TA-6366) on morphological change and mechanical property related to sodium ion permeability in the aorta of spontaneously hypertensive rats (SHRs) were examined, as compared with those of enalapril and captopril. Ten-week oral administration of TA-6366 (1 and 5 mg/kg/d) from 4 weeks of age impeded aortic media-thickening together with a rise in blood pressure in SHRs. Concomitantly, aorta weights in both groups were markedly decreased. The higher dose of TA-6366 almost fully suppressed the accelerated tension development induced by K(+)-free medium and decreased total sodium ion content in the aorta. These vascular effects of TA-6366 was more prominent than those of enalapril and captopril at 5 mg/kg/d. The difference in potencies on the above vascular parameters between TA 6366 and these drugs seemed to be mainly related to the difference in their antihypertensive activities. These results suggest that TA-6366 has preventive effects against progression of vascular diseases, particularly atherosclerosis, accompanied with hypertension. PMID- 1289502 TI - Transferring a practice ownership interest: the partial buy out. PMID- 1289503 TI - Sex roles in management: the impact of varying power of speech style on union members' perception of satisfaction and effectiveness. AB - Effective management has traditionally been associated with men and masculine characteristics. In this study, I focused on manager communication, specifically the perceived effects of stereotypical gender/power speech styles. Union members viewed and rated a male and a female manager on videotape using three gender/power speech styles: stereotypical masculine (powerful), stereotypical feminine (powerless), and mixed gender/power. Union respondents judged both the male and female manager using the mixed gender/power speech style as most effective and as being associated with the most satisfied employees. PMID- 1289504 TI - Factors affecting reactions to a rape victim. AB - We examined the influence of the sex of the subject reacting to the rape victim, the type of rape (stranger vs. acquaintance), the location of the rape (inside vs. outside the victim's home), and the victim's attribution concerning the cause of the rape, on undergraduates' reactions to a rape victim. American undergraduates (264 women, 230 men) read a Rape Crisis Center Intake Form, watched a videotape of a rape victim (an actress) describing her psychological and behavioral reactions to the rape, and completed three questionnaires assessing their reactions to the victim. Women were more supportive of the rape victim than were men, and the stranger rape evoked more chance and characterological attributions than did the acquaintance rape. A rape outside the home evoked more chance attributions than did an "inside" rape. The rape victim was rated as having been more traumatized by the experience if she made any causal attribution than if she made no attribution at all. PMID- 1289505 TI - Development and psychometric evaluation of the Primary Appraisal of Smoking Cessation Inventory. AB - For this study, we developed and evaluated the psychometric properties of the Primary Appraisal of Smoking Cessation Inventory (PASCI), a self-report measure designed to assess the perceived gains and losses associated with quitting smoking based on the theoretical model of stress described by Lazarus and Folkman (1984). We administered the 26-item PASCI and two other questionnaires to 244 current smokers and to 30 ex-smokers. Item analyses indicated that two items on the PASCI should be deleted due to low item-total correlations. A principal components analysis of the remaining 24 items identified two separate and independent factors, Losses and Gains, and scores on the subscales of both factors were internally consistent and stable over repeated administrations. The validity of the PASCI was established by examining the relationship between smoking status and scores on the PASCI subscales and by finding significant correlations between the PASCI and the Decisional Balance Scale (Velicer, DiClemente, Prochaska, & Brandenburg, 1985), a measure conceptually similar to the construct measured by the PASCI. We concluded that the PASCI is reliable and valid and can be used to investigate the relationship between primary appraisal and smoking cessation. PMID- 1289506 TI - Nature of romantic love in female adolescents. AB - In the present study, I intended to determine the similarity between Rubin's (1970) Love Scale components and five of Lee's (1976) six lovestyles in a relatively homogenous sample of 301 16- and 17-year-old British females. Items describing loving behaviors toward a particular individual were formulated to measure these lovestyles together with that of Ludus. The six orthogonal factors extracted from the correlation matrix of these and Rubin's items were called Love, Mutual Love, Respect, Similarity, Physical Attraction and Hostility. The results suggested that Rubin's Love Scale contained elements of Mania and Agape but none of Ludus, which could not be further differentiated. Rubin's (1970) Liking Scale, however, could be further subdivided into Respect (Pragma) and Similarity (Storge). PMID- 1289507 TI - Structure of the modern Japanese family: evidence from the results of a Doll Location Test by adolescents. PMID- 1289508 TI - Left ventricular mass regression in elderly hypertensives. AB - It is now recognized that left ventricular hypertrophy (LVH), often associated with hypertension, is itself a risk factor for coronary disease in the elderly. Although many agents are capable of controlling blood pressure, the ability of these agents to induce regression of left ventricular (LV) mass, and the effect of regression on diastolic relaxation and contractile indices in the elderly are less well known. Our study compared the ability of the calcium blocker, verapamil, and the beta-blocker, atenolol, to both control blood pressure (BP) and to induce regression of LV mass in older hypertensives. In addition, the influence of regression on resting diastolic filling and on cardiac output and ejection fraction during rest and mild upright bicycle exercise were determined. Forty-two hypertensives 60 years of age or above, without evidence of ischemic disease underwent 2-D echocardiographic evaluation of LV mass and gated blood pool scan determination of early diastolic filling, cardiac output and ejection fraction. They were then randomized to receive verapamil or atenolol during a four-week titration period so as to achieve a BP of less than 160/90 mm Hg. If BP was not controlled with either agent, chlorthalidone was added. Individuals whose BP was controlled continued on the protocol for six months. At that time, the echocardiographic and gated blood pool studies were repeated both on and after subsequent withdrawal of the study medications. Twenty-one patients were randomized to receive verapamil and 21 patients to receive atenolol. Blood pressure control was achieved with verapamil alone in 18 patients, but with atenolol alone in only 8 patients (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289509 TI - Combination therapy in hypertension. AB - In patients in whom monotherapy does not control blood pressure a second agent is required. Common combinations in clinical practice are a beta-blocker plus a diuretic, an angiotensin converting enzyme (ACE) inhibitor plus a diuretic, a beta-blocker plus a dihydropyridine calcium antagonist, and an ACE inhibitor plus a calcium antagonist. Since both ACE inhibitors and calcium antagonists are metabolically inert and exert favorable effects on target organ disease, their combination is of particular interest. When combined, these two drug classes have additive effects on antihypertensive efficacy, reduction of left ventricular hypertrophy, and protection of the renal circulation. However, whether or not these favorable pathophysiologic changes induced with combination therapy of ACE inhibitors and calcium antagonists will translate into a reduction of morbidity and mortality remains to be documented. PMID- 1289510 TI - Antihypertensive therapy in diabetic patients. AB - Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2 antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1289511 TI - Endothelin-induced vasoconstriction and calcium antagonists. AB - Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide, is one of the most potent of these factors, which can control local vascular tone. The peptide is formed from its precursor, big endothelin, via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1 and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to its specific receptor (ETA receptor and possibly ETB-receptor) which activate phospholipase C and lead to the formation of inositol trisphosphate, diacylglycerol and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to voltage-operated calcium channels via a Gi-protein. This linkage may explain why calcium antagonists inhibit endothelin-induced contractions in certain, but not other blood vessels. In large conduit arteries, such as the human internal mammary artery, endothelin-induced contractions are primarily mediated by release of intracellular calcium and hence, calcium antagonists do not markedly affect the response. In contrast, in the human forearm circulation, calcium antagonists of different classes do prevent endothelin-induced contractions. Similarly, in mesenteric resistance arteries of the rat, calcium antagonists can reverse endothelin-induced contraction suggesting that calcium antagonists are particularly potent in inhibiting endothelin-induced contraction in resistance arteries, where peripheral vascular resistance and hence, blood pressure is regulated. PMID- 1289512 TI - Effects of antihypertensive agents on carotid pulse contour in humans. AB - The aim of this study was to assess the influence of antihypertensive agents on arterial wave reflections (AWR) and carotid pulse pressure (PP) in humans. Twenty patients with hypertension (predominantly systolic) were studied. After one month of placebo therapy they were randomly assigned to atenolol (At) 50 mg/day or to nitrendipine (Ni) 40 mg/day. Carotid pressure waveform was recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Arterial wave reflections were quantified as the ratio of the height of the late systolic peak (delta P) to the total height of carotid pulse pressure wave as an augmentation index (delta P/PP). Travel time of the reflected wave (delta tp) was timed from the foot of the pressure wave to the foot of the late systolic peak. Atenolol and Ni were equally effective in reducing sphygmomanometric brachial artery blood pressure (BP). Whereas At (p < 0.05) and Ni (p < 0.01) reduced the carotid PP, Ni (p < 0.01) but not At significantly reduced delta P/PP. Both agents increased the delta tp (p < 0.01) and decreased aortic PWV (p < 0.01). Nitrendipine was associated with a decrease in left ventricular ejection time (LVET) (p < 0.01), while At increased heart period (p < 0.01) and LVET. The LVET/delta tp ratio decreased after Ni (from 3.25 +/- 0.77 to 2.42 +/- 0.73; p < 0.01) but did not change after At. The study shows, that for the same effect on peripheral BP, Ni has a more pronounced effect on pressure wave in central arteries, resulting from an improvement in the timing between the ventricular ejection and AWRs. PMID- 1289513 TI - The antihypertensive effect of verapamil in patients with chronic renal failure. AB - The calcium antagonist verapamil has been demonstrated to be effective in reducing hypertension in patients in whom sodium intake was not restricted. The present study evaluated the effect of verapamil in reducing hypertension in patients with chronic renal failure on low or high sodium diets. Also, the present study evaluated the effect of verapamil on proteinuria in chronic renal failure patients who were administered a normal and low protein diet. The results reveal that verapamil-SR 240 mg daily is effective in reducing hypertension in patients with chronic renal failure and the effect of verapamil is equal in patients on a high or low sodium intake. In addition, verapamil-SR 240 mg daily is effective in maintaining reduced proteinuria in chronic renal failure patients on low protein diet and may prevent proteinuria in such patients on a normal protein diet. Therefore, verapamil-SR 240 mg daily appears to be an excellent choice for the treatment of hypertensive chronic renal failure patients. PMID- 1289514 TI - Atherosclerosis and calcium antagonists: the VHAS. The Verapamil-Hypertension Atherosclerosis Study (VHAS) Investigators. AB - Whether or not some classes of antihypertensive drugs have an anti-atherogenic action independent of the antihypertensive one has been investigated through a large series of experimental studies, primarily involving calcium antagonists. Most experimental investigations have shown a significant anti-atherogenic action of calcium antagonists, but only when the drug is administered simultaneously with the atherogenic stimulus (mainly cholesterol feeding). When the drug is administered weeks or months after the beginning of the atherosclerotic process (as in the Watanabe heritable hyperlipidemic rabbit), with a single exception, no antiatherogenic effect has been shown. The few clinical studies completed so far have been on symptomatic coronary patients. Little is known of the effects of calcium antagonists on asymptomatic lesions in the carotid arteries of hypertensive patients, in whom carotid plaques can be identified and followed-up by non-invasive ultrasound techniques. However, two such trials are underway. The Verapamil in Hypertension Atherosclerosis Study (VHAS) is an ongoing randomized trial, comparing the antihypertensive efficacy of verapamil 240 mg SR with chlorthalidone 25 mg in 1,464 essential hypertensives aged 40-65 years. In a random subgroup of patients (500), who will be followed for three years, B-mode ultrasonography is being carried out blindly to evaluate the effect of the two drugs on carotid wall thickness and on carotid plaques, when present. Preliminary baseline data are available in 440 of the hypertensive patients in whom ultrasound investigation was performed. The mean (+/- SD) age of these patients was 53.7 +/- 6.9 years; 32.5% had echocardiographically normal carotid walls; 30.9% showed intima-media thickening; and 36.6% had one or more plaques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289515 TI - Ambulatory blood pressure monitoring and antihypertensive treatment. AB - Ambulatory blood pressure monitoring is becoming increasingly popular among clinicians and investigators because of its potential to overcome the well-known limitations inherent to conventional blood pressure measurement. This paper will focus on the use of this approach in the evaluation of antihypertensive treatment. It will be argued that due to lack of prognostic validity and high cost, ABPM should not be employed routinely in treating hypertensives. It should always be employed, however, for the evaluation of the efficacy of new hypertensive drugs for which its superiority over sphygmomanometry is indisputable. This is exemplified by the results of a recent multicenter, double blind, parallel group study on the effect of verapamil SR 240 mg, enalapril 20 mg and nitrendipine 20 mg and placebo, all administered once a day for eight weeks. Compared to placebo, all drugs reduced 24-hour mean blood pressure sufficiently. The reduction was evident throughout the daytime but nighttime blood pressure was more effectively lowered by verapamil and enalapril than by nitrendipine, documenting a difference that was not visible by using conventional measurements. PMID- 1289516 TI - More Q&A on the bloodborne pathogens standard. PMID- 1289517 TI - "You gave me back my life...". PMID- 1289518 TI - Sharps disposal update. A study of one regulated medical waste (Sharps) in the dental office: an interim report. PMID- 1289519 TI - "Making do" with what you have. PMID- 1289520 TI - Financing your office redesign. PMID- 1289521 TI - Should I move my office? "Must-do" strategies for making a decision you can work with. PMID- 1289522 TI - What should I do with my medical waste? PMID- 1289523 TI - "Empowering" your dental team. PMID- 1289524 TI - Boost your practice with infection control patient education! PMID- 1289525 TI - You are not alone. PMID- 1289526 TI - Infection control and exposure control: are these terms interchangeable? PMID- 1289528 TI - Tomorrow's dentist/carrier relationship. PMID- 1289527 TI - What to do after an exposure incident. PMID- 1289530 TI - How the disciplinary process works. PMID- 1289529 TI - The "magic" of mirrors. PMID- 1289531 TI - A survey of mouthrinse use by patients referred to a periodontal practice. PMID- 1289533 TI - Crevicular fluid in health and disease. PMID- 1289532 TI - Pregnancy and periodontal health. PMID- 1289534 TI - The Phnom Penh experience. PMID- 1289535 TI - A review of mouthwashes available in Dunedin and their use by the public. PMID- 1289536 TI - Special report: evaluating the benefit-risk of dental implants provides informed consent. Part II. PMID- 1289537 TI - The pharmacologic management of maxillary sinus elevation surgery. AB - The edentulous posterior maxilla often has inadequate bone for endosteal implants. Therefore, implant placement in this area often requires the manipulation of maxillary sinus anatomy. The development of infection following sinus elevation procedures can occur from contamination of the site by oral and/or sinus pathogens or secondary infection from a maxillary sinusitis. The prevention and prompt treatment of complications associated with this surgery can contribute to increased success in this area. The prophylactic use of systemic and local antibiotics and glucocorticosteroids can reduce the risk of infection. If infection develops, culture and sensitivity testing is indicated, with the prescription of empiric antibiotic therapy and decongestants. A knowledge of clinical pharmacology and its therapeutic application is essential for the predictable management of sinus elevation surgery. PMID- 1289538 TI - Clinical response of hard tissue replacement (HTR) polymer as an implant material in oral surgery patients. AB - This study evaluated the performance of a synthetic implant material, Hard Tissue Replacement Polymer, for: (1) ease of handling, (2) compatibility with bone and soft tissue, (3) stability of augmentation over time, and (4) development of untoward effects. HTR (a registered trademark of HTR Sciences, a division of United States Surgical Corporation, Norwalk, CT 06856) was implanted into 34 patients by means of five different surgical procedures. The material was found to be easy to manipulate during surgery. Tissue and bone compatibility, defined as absence of inflammation, was present in 32/34 surgical sites (94%). In extraction sites during the 18-month follow-up, no measurable decrease in bone height or width was seen. One patient with a large periodontal endodontic defect developed a post-operative infection necessitating extraction of the tooth. No induction of bone was seen in response to placement of HTR material. PMID- 1289539 TI - Load characteristics and design principles of mandibular tripodal subperiosteal implants. PMID- 1289540 TI - Part I. Reconstruction after total mandibulectomy with free cranial and microvascular iliac crest grafts as preparation for implants. AB - A young Ecuadorian girl underwent a total mandibulectomy due to infected fibrous dysplasia. In the subsequent 16 years, she was unable to speak intelligibly or masticate, surviving on liquids alone. After referral to the United States, the patient underwent six major surgical procedures that reconstructed her mandible from cranial and microvascular iliac crest grafts. The reconstruction improved her appearance and prepared her for insertion of dental implants and the eventual construction of a prosthetic device. These resulted in both functional and esthetic benefits. PMID- 1289541 TI - Part II. Mandibular reconstruction: combined intra-oral and in vitro placement of osseointegrated implants into a free and vascularized bone graft. AB - A 28-year-old Hispanic girl underwent a complete mandibular reconstruction many years following full mandibulectomy for fibrous dysplasia. Because of infectious complications, both free cranial and microvascular iliac crest grafts were used. The patient had osseointegrated implants placed directly into the grafted mandible. Osseointegrated implants were also placed into a segment of free iliac crest bone, in vitro, and then grafted laterally onto the reconstructed mandible. Prosthetic reconstruction was then carried out to restore the patient to normal function, health, comfort, and esthetics. PMID- 1289542 TI - Solving the problem of violated intermaxillary space caused by poor pre-planning and improper placement of endosseous implants: a case report. AB - Every dental implant patient needs thorough evaluation and pre-surgical planning. It is imperative for the practitioner to have absolute knowledge of the implant system to be used. Nevertheless, sometimes we find ourselves in very difficult, almost unrestorable, situations. Often, we cannot rely on the implant manufacturers, and we have to be ready to customize some parts in order to solve difficult clinical situations. This case report shows how customized magnet keepers were fabricated by use of plastic IME's as casting patterns in order to solve the problem of violated intermaxillary space. PMID- 1289543 TI - Soft-tissue healing: pressure orthotic mask--case study. PMID- 1289544 TI - The osteointegrated prosthesis--combination of osteointegrated implants and natural teeth in fixed prostheses. PMID- 1289545 TI - Report from Israel: how to resolve a complex case using implant procedures. PMID- 1289547 TI - Statistical tracking of the various implant modalities. PMID- 1289546 TI - Report from Yugoslavia: failure of a maxillary porous hydroxylapatite implant six years after implantation. PMID- 1289548 TI - Correlative transmission electron microscopic and scanning electron microscopic observations of the tissues supporting endosteal blade implants. AB - Correlated scanning electron microscopic (SEM), routine transmission electron microscopic (TEM), and high-voltage transmission electron microscopic (HVEM) observations demonstrated that one-stage and two-stage endosteal blade-type implants were well-supported by mandibular tissues after five months of unloaded healing in dogs. Areas of the implants were apposed directly by mineralized tissues without any apparent interposed unmineralized connective tissue. Other areas of the implants were apposed by narrow areas of unmineralized tissue, often containing osteoblasts. These unmineralized areas were interposed between the implant and a supporting mineralized matrix. A healthy mix of tissues, which represented a dynamic osseous complex, supported these serviceable blade-type dental implants. This study, for the first time in the dental implant literature, utilizes HVEM stereology for evaluation of the bone-implant interface. PMID- 1289549 TI - Finite element analysis (FEA) studies in 2.5-mm round bar design: the effects of bar length and material composition on bar failure. AB - The round bar/overdenture prosthesis is commonly used in the restoration of the totally edentulous implant patient. The length of bar span and types of alloys used in clinical cases have raised questions related to beam flexure and its role as a possible etiology of reported clinical failures in cast alloy systems. Three dimensional finite element analyses were thus conducted on a 2.5-mm round bar for investigation of mechanical performance with respect to failure potential as a function of bar length and bar material property. Specifically, three bar lengths (6 mm, 12 mm, and 18 mm) and three alloy materials were analyzed, representing a clinical range of usage. The ends of each bar were modeled fixed to a 2.5-mm coping which was attached to a 3.8-mm root-form-type implant. The implant was modeled rigidly fixed in a representative block of bone. A 200-N occlusal force was applied to the model, as would be transmitted through an attachment clip, 5 mm in length, for the three respective bar lengths. The results of these analyses suggested possible yielding (or failure) in the 18-mm case. Bar length was found to play a stronger role in the adequacy of the overall design as compared with changing material properties in the range of alloy stiffnesses tested. Factors of safety with respect to static yield strength ranged from 2.82 to 66.46 for the designs evaluated. Fatigue factors of safety ranged from 1.63 to 38.88. A factor of safety of 5 or greater is suggested for the design of round bar systems in order for bar failure to be prevented. PMID- 1289550 TI - Short-term plasma-cleaning treatments enhance in vitro osteoblast attachment to titanium. AB - The purpose of this research was to characterize the in vitro cellular behavior of osteoblast-like cells on titanium surfaces prepared with argon plasma-cleaning (PC) treatments for various lengths of time. The highest levels of cell attachment were observed for surfaces which had been plasma-treated for one min. Surface analyses indicated that although PC treatments dramatically improved surface wettability, the presence of inorganic contaminants was observed with longer treatment times and may have interfered with cell attachment. Further work is suggested to investigate the longer-term phenotypic expression of osteoblasts when grown on implant surfaces. PMID- 1289551 TI - Early uncovering of HA-coated cylinder implants: case report of an in vivo shear strength test. AB - A new approach was used to test the readiness of an HA-coated implant for commencement of prosthetic procedures after two months of bone healing in humans. A torquing device was used for clinical measurement of the shear resistance of the supporting bone. It was found that the bone was capable of resisting a shear force just slightly greater than that which was necessary to produce displacement of implants placed in dog femurs with a comparable bone-healing period and with healing to full maturity. This report suggests that it may be feasible to uncover HA-coated implants after two months of bone healing. PMID- 1289552 TI - Dental implant treatment in a severely compromised (irradiated) patient. AB - When faced with a patient with relative medical or psychological contra indications, the practitioner may be tempted to withhold dental implant treatment because of the risks. Yet, for some highly motivated but compromised patients, the potential benefits of implant treatment can be an overriding consideration. In the case presented here, a 56-year-old patient who had undergone two series of radiation therapy and surgery for recurring cancer of the tongue was treated first with a subperiosteal, and, when the subperiosteal was removed after six years, the patient was treated with endosseous implants. This treatment significantly improved the patient's life without further negative effect on her medical condition. PMID- 1289553 TI - A surgical-prosthetic procedure using implants to salvage a failed mandibular rehabilitation. PMID- 1289554 TI - Fabrication of soft-tissue models for implant restorations. PMID- 1289555 TI - Spark erosion technology. PMID- 1289556 TI - Overview of factors important in implant design. AB - Forty-two percent of the population over the age of 65 is totally edentulous. The use of dental implants as a means of treating these patients has accelerated in the last decade, and there are now 300,000 dental implants used in the United States. It is therefore imperative that a greater understanding of the parameters which govern the long-term success of implants be developed. In order for the effectiveness of implants to be better quantified, a fundamental, quantitative understanding of the physical parameters governing the complex synthetic material/tissue aggregate is needed. The design of an "optimal" implant requires the integration of material, physical, chemical, mechanical, biological, and economic factors. The approach taken for a specific property objective to be met should be based on a materials science approach, in which the synergistic relationships among processing, composition, structure, and properties are characterized. Implant success is a function of biomaterials and biomechanical factors, including: materials and material processing; mechanisms of implant/tissue attachment; mechanical properties; implant design; loading type; tissue properties; stress and strain distributions; initial stability and mechanisms of enhancing osseointegration; biocompatibility; and surface chemistry, mechanics, and bone-binding ability of the implant. This paper presents an overview of physical parameters important to implantology. Following a general presentation of implantology concepts, the physical parameters listed above are discussed in greater detail. PMID- 1289557 TI - Micromechanics of implant/tissue interfaces. AB - A series of finite element models was developed for evaluation of the micromechanics of implant/tissue interfaces. Conventional finite element global models of a dental implant, assuming a continuum implant/bone interface, were developed so that general stress patterns in the implant and surrounding tissue could be obtained. Stresses in bone were concentrated on the alveolar crest and apex region for all global models having a direct bone/implant contact. The addition of a 100-microns-thick layer of fibrous tissue into the bone/implant interface concentrated the stresses in the middle third of the bone adjacent to the implant surface. Stresses in the middle third were ten times higher than in the cases without fibrous tissue. Interfaces modeled under the assumption of a volume-weighted average material stiffness of bone tissue and metal confirmed these general stress patterns, but provided no stress details of the interfacial zone. Finally, the equivalent material constants of the interfacial zone with and without fibrous tissue were calculated by homogenization theory. From these equivalent constants, local strains around single threads were calculated. These equivalent material properties are sensitive to the microstructure. Therefore, it is now possible for stress patterns within the interfacial zone to be quantified and the local micromechanical behavior around individual surface structures for whole implants accounted for. PMID- 1289558 TI - A brief introduction to advanced surface modification technologies. AB - Techniques for the modification of surfaces are evolving rapidly. In implantology, few of the newer surface modification techniques have been used. The purpose of this paper is to provide an introduction to advanced surface modification processes that could be useful in dental implant manufacturing. There are three general techniques used to modify surfaces: add material, remove material, and change the material already present. Several processes for the addition of material to surfaces are described in this paper. Two new processes that can create relatively thick coatings are sol-gel and plasma-spraying. Several new processes making thin film coatings (sub-micron) have come from the electronics and optics industries. These are vapor deposition techniques, where the coating material condenses onto a surface from a vapor. The three basic vapor deposition techniques are: evaporation, sputtering, and chemical vapor deposition. New processes for the removal of material from surfaces, often for cleaning purposes, are glow discharge treatment and sputter-etching. Surface properties can also be changed without addition or removal of material by use of laser and electron beam thermal treatments. Ion implantation can be used to add material to surfaces, modify coatings, and change microstructures. The techniques outlined in this paper have great potential for improving implants. PMID- 1289559 TI - Radiofrequency gas plasma (glow discharge) disinfection of dental operative instruments, including handpieces. AB - The radiofrequency-stimulated argon gas plasma (glow discharge) technique, already well-known for surface cleaning and activation of adhesion, was investigated for determination of its separate potential for rapid disinfection of dental operative instruments. Disinfection effectiveness was judged from diminished post-treatment recovery of viable organisms from the instruments agitated in saline. Streptococcus salivarius, Bacillus stearothermophilus, and Escherichia coli were used as primary contaminant organisms, dried from gelatin thickened laboratory cultures onto the instruments and not subjected to any preliminary cleaning steps. Significant disinfection was obtained, with no sensible temperature increases, in under 10 minutes in laboratory apparatus consuming fewer than 5 Watts of power per cycle. Also, clinically used and deliberately-saliva-contaminated high-speed handpieces were gas-discharge treated, with their resultant rapid disinfection noted by complete suppression of the viability of any transferred natural contaminant organisms within two minutes. With regard to preservation of instrument quality, it was also shown that this low-temperature gas-discharge method provides the noted substantial disinfection without deterioration of sharp edges. Work now in progress suggests that the method can provide cool, rapid, and complete sterilization when hydrogen peroxide vapors are present in the gas plasma used for treatment of instruments first given the normally recommended thorough pre-cleaning. PMID- 1289561 TI - Tatum custom ramus frame implant: multiple options including treatment for combination syndrome. AB - The advantages offered by the Tatum custom ramus frame include its extended posterior arms, its ability to form a solid interface, and its availability in numerous sizes. It has solved some of the problems associated with the earlier models of the ramus frame. It offers stable support for a removable prosthesis in the completely edentulous mandible. In cases of combination syndrome, where a hopeless anterior dentition must be removed, a ramus frame can be placed immediately into the extraction sites. In a severely atrophied alveolar ridge, bone augmentation can be performed simultaneously with the ramus frame placement surgery. This implant device can, moreover, restore the patient's stomatognathic system to comfort, function, and pleasing esthetics quickly and economically. Furthermore, statistics show a 97% survival rate over 18 years (Tatum, 1992). Although the surgical procedure for the custom ramus frame is more complex than that for root-form and some subperiosteal procedures, and patients must be carefully selected, the custom ramus frame provides improved strength and load resistance. PMID- 1289560 TI - Biological requirements for material integration. AB - The recognition that synthetic devices can provide functional replacements for failed teeth, or for previously edentulous areas, has resulted in increased emphasis being placed on understanding of the interactions between synthetic materials and host tissues in order for the success of these devices to be optimized. A key to achievement of an optimal biological interface between the implant and the surrounding tissue is through an understanding of host response to materials. This article reviews the biological requirements for implant-tissue integration, with specific focus on the role of adhesion molecules and cytokines (growth factors) in this process. Adhesion molecule/cytokine interactions are discussed, and in particular the possible role for osteopontin, an adhesion molecule as well as a cytokine, is considered in wound healing. Finally, the causes of peri-implantitis are discussed, and methods of decontamination are presented. The decontamination methods focus on enhancement of cell adhesion and integration to the altered implant surface. PMID- 1289562 TI - Force transfer in implant dentistry: basic concepts and principles. AB - The mechanism and efficiency of force transfer by dental implants to contiguous biological tissues are clearly important determinants in the development of the implant-to-tissue interface and, indeed, implant longevity. Whether a clinician seeks to gain a better understanding of implant design rationale and/or to implement biomechanics concepts in patient care, a fundamental, yet clinically relevant, understanding of biomechanics is required. A primer in force transfer is thus presented, with particular attention focused on implications for the long term success of dental implants and restorative procedures. Forces and their components, moments, force transfer mechanisms, impact, and stress-strain relationships all influence clinical decisions and treatment plans. PMID- 1289563 TI - Dental implants. PMID- 1289564 TI - A study of the effect of magnetized water on enzyme activities by potentiometric enzyme electrode method. AB - A very promising glutamate decarboxylase electrode, which has linear response range of 5.6 x 10(-5)-1.2 x 10(-2) mol/L. Nernstian slope of 50 mV/decade, detection limit of 3.2 x 10(-5) mol/L and response time less than 3 min, has been designed to observe and evaluate quantitatively the effect of magnetized water on enzyme activities by potentiometric enzyme electrode method. It was found that the activity of glutamate decarboxylase can increase by 30% in magnetized water. The mechanism of increased enzyme activity was discussed in the present paper. Such a new finding will probably lead to some new explanations for the physiological and biological mechanism of the effect of magnetized water on living organisms, thus providing a new approach to the study of the effect of magnetized water. PMID- 1289565 TI - Effects of cigarette smoking on the function of metabolizing arachidonic acid and angiotensin I in the isolated perfused rat lungs. AB - The effects of acute and chronic cigarette smoking on the metabolism of exogenous arachidonic acid (AA) and angiotensin I (AI) in perfused isolated rat lungs were studied. The results showed that acute cigarette smoking did not alter the contents of 6-keto-PGF1 alpha (the stable metabolite of PGI2) and TXB2 (the stable metabolite of TXA2) in the effluent and the increment of pulmonary artery pressure (delta Ppa) caused by AA. The conversion of A I into A II was significantly increased (P < 0.01), while the delta Ppa induced by A I injection was obviously decreased as compared with controls (P < 0.05). After cigarette smoke exposure for 30 days, the delta Ppa caused by AA or A I did not differ from that of controls, but the contents of 6-keto-PGF1 alpha and A II increased more markedly than those in non-smoking rats (P < 0.05). It is suggested that acute and chronic cigarette smoking in rats can promote the lung function of converting A I into A II, chronic smoking can increase the lung function of metabolizing AA into PGI2. PMID- 1289566 TI - Effects of microinjection of L-glutamate into locus coeruleus complex area on respiration. AB - The experiments were performed on 55 rabbits vagotomied, anesthetized with urethane and immobilized with flaxedil. Injection of L-glutamate (L-glu) into the locus coeruleus complex (Lc-Sc) area led to a marked increase in respiratory frequency (RF) and phrenic nerve discharge rate (phr.d) (16 +/- 3.5% and 6.5 +/- 2.5%; P < 0.01 and P < 0.05, respectively), a decrease in inspiratory and expiratory duration, and no obvious change in blood pressure (Bp) was observed. While prazosin (0.5 micrograms/microliters), yohimbin (4 micrograms/microliters) and propranolol (2 micrograms/microliters) were preinjected into the nuclei tractus solitraii (NTS) respectively, the above-mentioned effects of L-glu on respiration was blocked. These results indicate that the excitation of neurons in the Lc-Sc can induce an increase in RF and phr. d and the excitative effect of L glu on RF was mediated by alpha 1, alpha 2 and beta-receptors in the NTS, while the effect on phr.d was mediated differently. PMID- 1289567 TI - Effects of electroacupuncture of "zusanli" acupoint on high blood pressure and blood hyperviscosity in stress rats. AB - Elevation of blood pressure (BP) and blood viscosity (BV) was induced in unanesthetized Wistar rats by fixing and hanging. Electroacupuncture of "Zusanli" acupoint or microinjection of GABA (60 micrograms/10 microliters) into the IV ventricle of the brain could lower the high BP and BV induced by fixed-hanging, which could be blocked by a microinjection of GABAA receptor antagonist bicuculline (60 micrograms/10 microliters). The results showed that the depressant effect of electroacupuncture of "Zusanli" acupoint on high BP and blood hyperviscosity induced by fixed-hanging might be mediated by the activation of GABAA receptors in the brain. PMID- 1289568 TI - The screening diagnosis of tetrahydrobiopterin deficient phenylketonuria. AB - Since 1990, 20 diagnostically confirmed phenylketonuria (PKU) patients have been screened with a tetrahydrobiopterin (BH4) loading test, in which plasma phenylalanine and urinary pterin metabolites were investigated, ind activity of dihydropteridine reductase (DHPR) was determined as well. The results showed that there was no statistical difference between the concentrations of plasma phenylalanine before and after BH4 (20mg/kg) administration in all patients, and values of urinary neopterin and biopterin were within the range of classic PKU. All patients but one had normal activity of DHPR in red cells. This suggests that incidence of BH4 deficiency in PKU patients amounts to five percent (1/20) which is almost the same as reported abroad. PMID- 1289569 TI - Hypothalamic-pituitary function assessment in children by a combined stimulation test. AB - We utilized a combined stimulation test using insulin, thyrotropin-releasing hormone, gonadotropin-releasing hormone and levodopa to assess multiple pituitary hormones including growth hormone, thyrotropin, prolactin and gonadotropins in 32 children of short stature and 18 girls with early appearance of puberty. It was found that this combined stimulation test can assess multiple hormone responses with satisfactory results in a single 90-min test. Compared with any of those laborious classic stimulation tests alone, it is easier to be carried out and willingly accepted by children. PMID- 1289570 TI - Changes in serum fibronectin levels at delivery in pregnant women and their fetuses with idiopathic fetal growth retardation. AB - We determined maternal and neonatal umbilical artery serum concentrations of fibronectin (Fn) in 15 pregnant women with idiopathic IUGR (Intrauterine growth retardation) and 17 normal pregnant women at the time of delivery, by use of a rate nephelometric procedure. The results showed that the maternal serum levels of Fn in pregnant women with idiopathic IUGR were significantly higher than those in normal pregnant women at the time of delivery (P < 0.01), but umbilical artery serum concentrations in the two groups were not significantly different (P > 0.05), suggesting that the significant increase in maternal serum levels of Fn appeared to be related to uteroplacental vascular endothelial cell lesion, formation of microthrombi and deficiency of placental perfusion. PMID- 1289571 TI - Monocrotaline-induced structural remodeling of the intra-acinar pulmonary arteries and pulmonary hypertension. AB - The monocrotaline-induced structural changes of small pulmonary arteries in rat and their relationship with pulmonary hypertension and right ventricular hypertrophy were observed by determining the right ventricular systolic pressure, and by light and electron microscope and morphometry. One to 38 days after last injection of monocrotaline (MCT), a medial thickening and lumen marrowing of the circular muscular arteries (CMA), accompanying terminal (TB) and respiratory bronchioles (RB), were found. And there after the lumen of CMA, accompanying TB, became dilated, and its medial thickness (MT) decreased, whereas the histopathologic changes of the partially muscular arteries (FMA), accompanying RB, became severe, their MT increased continuously, and finally reached the peak value on Day 50. At the first day after last MCT treatment, inflammation and muscularization were found in PMA and nonmuscular arteries (NMA), and became more severe with the cause of disease. Therefore, the intra-acinar pulmonary arteries, both CMA and PMA, increased in number while the NMA decreased in number significantly because of the structural remodeling. Four days after MCT treatment, the right ventricular systolic pressure began to rise, and reached its peak value on Day 50. Eight days after MCT injection, right ventricular hypertrophy developed, and became most significant from Day 23 to Day 30. The results suggest that structural remodeling, i.e. muscularization, of intra-acinar pulmonary arteries plays an important role in the development of pulmonary hypertension and right ventricular hypertrophy. PMID- 1289572 TI - A cytogenetic study of five rare karyotypes. AB - The results of chromosome analysis of 5 cases from our genetic counseling showed that among these patients, 4 had two or more repeated spontaneous abortions. Structural abnormalities with the karyotypes 46, XX, t(1;11)(q42;q13), 46, XY, t(17;19)(q21;p13.3), 46, XY, t(4;5)(p13;q35) were reported for the first time in the literature abroad. The karyotypes 46, XX, t(16;18)(q24;q21), 46,XX, t(3;8)(p21;q24.3) were reported for the first time in the literature at home. A discussion is made on the origin of chromosome aberration and the cause of repeated spontaneous abortions. PMID- 1289573 TI - Comparison between laser and electrical ablation of ventricle in dogs: hemodynamic, pathologic and electrocardiographic observations. AB - To characterize and compare the pathologic, hemodynamic and electrocardiographic changes of both transcatheter laser and electrical energy on ventricle, 36 subendocardial myocardium lesions were induced at energy 60, 120 and 240 Joules by either transcatheter laser irradiation or electrical shock in 7 anesthetized dogs. The following results were observed: 1) Both laser and electrical ablation on myocardium created nonhomogeneous myocardium injury, but laser ablation caused mainly focal tissue vaporization and necrosis, while electrical shock induced widespread tissue degenerations; 2) Both laser and electrical induced-lesion dimensions increased parallel to the total dosage of energy; 3) Laser ablation caused mainly (90%) single ventricular premature beats and 86% of them occurred within the first minute after energy discharged, while ventricular tachycardias were found in any electrical energy groups; ventricular fibrillations occurring during laser and electrical ablation were 5% and 13% respectively (P < 0.01); 4) A decrease in aortic blood pressure and an increase in central venous pressure induced by laser ablation were significantly less than that produced by the same amount of electrical energy (P < 0.01). Our preliminary results have shown that transcatheter laser ablation has great potential for becoming a practical method in the management of refractory tachycardias. PMID- 1289574 TI - An experimental study of trachea anastomosis in rabbits using carbon dioxide laser. AB - A technique of sutureless trachea anastomosis in rabbits using carbon dioxide laser was reported herein. In 6 rabbits with laser-assisted trachea anastomoses, only one was found to have slight anastomotic stenosis after operation, whereas 6 rabbits with conventional sutures all were found to have anastomotic stenosis. Results show that laser-assisted trachea anastomosis has certain advantages over the conventional suturing technique, thereby finding wide application in clinical tracheal reconstruction and lung transplantation. PMID- 1289575 TI - A clinical application of artery-including silicone tubing to peripheral nerve defect. AB - 7 cases of 11 peripheral nerve defects (5 median nerves, 5 ulnar nerves, and 1 radial nerve) were repaired through artery-including silicone tubing. The nerves have gaps within 3 cm in 9, and 3 to 5 cm in 2. Repairing the defect's location, 4 of them were below the axilla; 1 at the upper 1/3 part of the forearm and 6 at the lower part of the forearm. The duration of injuries was from 4 to 7 months, except one case lasting over a year. Six patients with 9 nerves involved had adequate follow-up of 6 to 9 months. One patient with 2 nerves was lost to follow up. The results were excellent in 5 nerves (M4S3), good in 2 (M3S3), and poor in 2 (M1S1). PMID- 1289576 TI - Surgical treatment of double-chamber right ventricle and its associated anomalies. AB - A report on the results of surgical treatment of 5 cases of DCRV and its associated anomaly was presented in this paper. No definite diagnosis of DCRV was made prior to operation. It was found that 2 cases had DCRV as an isolated anomaly, another 2 had the disease associated with VSD, and the remaining 1 had DCRV with right ventricle to left atrium cannulation. Muscular membrane septum type was found in 3 cases, and muscular bundle type in 2.4 cases diagnosed as having DCRV or DCRV with other heart anomalies during operation were treated properly and discharged fully recovered. 1 case died of acute heart insufficiency. Pathologic anatomy and physiology, associated anomalies of DCRV, and some experience with the operative approach were discussed in this article. PMID- 1289577 TI - Effects of acute ingestion of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction in dogs--role of leukotrienes. AB - The effects of acute intragastric administration of ethanol on hemodynamics and hypoxic pulmonary vasoconstriction were studied in spontaneously breathing dogs. The dogs were given 0.5 g/kg of 10% ethanol (v/v) in 5 min. Hemodynamic measurements were obtained before and 30 min after ingestion of ethanol. Mean pulmonary arterial pressure and pulmonary vascular resistance increased markedly after ingestion of ethanol, and hypoxic pulmonary vasoconstriction was augmented significantly by ethanol as well. Diethylcarbamazine citrate (DEC), a lipoxygenase inhibitor, inhibited these effects of ethanol in a dosage of 200 mg/kg. The above findings suggest that ethanol can induce pulmonary vasoconstriction, which may be predominantly mediated by leukotrienes (LTs). PMID- 1289578 TI - Oncogenes, molecular biology and the head and neck surgeon. AB - Advances in the treatment of head and neck cancer in the last 15 years have been largely limited to those that impact on patient morbidity while patient mortality statistics remain static. The advent of new technologies in molecular biology and immunology may provide the head and neck oncologist with the tools to impact on patient survival. The head and neck surgeon of the future will be required to have a basic understanding of their potential applications and limitations. PMID- 1289579 TI - [Antibacterial activity of rokitamycin against fresh clinical isolates]. AB - We obtained bacterial strains which were clinically isolated and identified from outpatients with various infections in medical institutions throughout Japan. Possible antibacterial activities of rokitamycin (RKM) were examined against these isolates. Minimum inhibitory concentrations (MICs) were determined through a comparative study with reference drugs. The results of the study are summarized as follows. 1. Resistance patterns of 400 isolates which were highly resistant to macrolides (MLs) with MIC values > 100 micrograms/ml were classified into 55 patterns. Staphylococcus spp. showed cross resistance to 14-membered ring MLs with 100% cross resistance observed between erythromycin (EM) and clarithromycin (CAM), and 85.2% between EM and oleandomycin (OL). Fewer isolates showed strong resistance to 16-membered ring MLs than to 14-membered ring MLs. Cross resistances observed among the Staphylococcus isolates were 100% between acetylmidecamycin (MDM-AC) and kitasamycin (leucomycin (LM)), 93.9% between MDM AC and josamycin (JM), and 53.3% between MDM-AC and RKM. Streptococcus spp. and Peptococcus spp. showed very similar resistance patterns to both 14- and 16 membered ring MLs, but resistance patterns to RKM were quite different. Most of anaerobic streptococci and Bacteroides fragilis group had similar resistance patterns to 14- and 16-membered ring MLs, but in some cases a pattern similar to that of Staphylococcus spp. was observed. 2. When ML-resistant bacteria isolated during 1975 to 1980 were compared to those isolated in 1986 and 1989, it was observed that resistance of Staphylococcus aureus remained almost unchanged, that of Streptococcus pyogenes was lower in the later years than during 1975 to 1980, but that of Streptococcus pneumoniae increased. 3. Most of ML-resistances of the resistant isolates were inducible, but extents of induction varied depending on drugs tested. Strong inductions were observed when 14-membered ring MLs were used, but inductions were minimal with 16-membered ring MLs. RKM appeared to induce resistance to the least extent. From these results, it appears that the RKM is quite useful clinically even in the 1990s. PMID- 1289580 TI - [Clinical evaluation of cefprozil in children]. AB - Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin, was evaluated for its efficacy and safety in 42 children with bacterial infections (Table 1), and the following results were obtained. 1. CFPZ was administered in 3 or 4 divided doses at daily dosages ranging from 15.3 to 60.0 mg/kg to 42 patients (19 cases of acute tonsillitis and/or laryngitis, pharyngitis, 13 cases of pneumonia, 2 cases each of suppurative cervical lymphadenitis and UTI, and 1 case each of scarlet fever, acute otitis media, suppurative parotitis, impetigo contagiosa, furuncle and acute enteritis) and the following clinical results were obtained: excellent; 24 cases, good; 14 cases, fair; 4 cases. The overall efficacy rate was 90.5% (Table 3). 2. MICs of CFPZ against 50 strains of isolated organisms are shown in Table 4. In 19 cases out of 28 cases examined, causative organisms were successfully eradicated and strain of Staphylococcus aureus was decreased in 1 case. 3. Diarrhea was observed in 2 cases (cases 8, 11). In case 8, the symptom disappeared spontaneously. Case 11 improved immediately after the administration of the drug was stopped. Among 39 children who went through laboratory tests, eosinophilia which seemed to be related to the administration of this drug was observed in 2 cases (cases 29, 38). Slight elevations of S-GOT and S-GPT were found in 1 case (case 22) (Table 7). 4. These data suggest that CFPZ is a safe and useful new antibiotic in the treatment of children with susceptible bacterial infections. PMID- 1289581 TI - [Clinical evaluation of a new oral cephalosporin, cefprozil, in pediatrics]. AB - Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin, was evaluated for its antibacterial activity and clinical efficacy. Thirty-four patients were treated with 7.7-36.2 mg/kg per day of CFPZ divided into 3 times. A total of 33 patients including 3 with acute pneumonia, 2 with acute bronchitis, 17 with acute upper respiratory tract infections, 4 with urinary tract infections, 1 with suppurative lymphadenitis and 6 with other soft tissue infections were evaluated for clinical efficacy except for 1 patient whose general conditions were too serious to continue to be treated with orally medication. Clinical effects were excellent in 8 patients and good in 23 but 2 cases were excluded because they were suspected for viral infections, hence the overall efficacy rate was 100%. Bacteriological responses were confirmed on 6 (66.7%) strains which were eradicated by the treatment out of 9 strains identified. CFPZ showed stronger antibacterial activities than those of cefaclor. Side effects or abnormal laboratory test results were observed in 2 patients; nausea and pallor of face in 1 patient and an increase of eosinophil in 1. The above findings suggest that CFPZ is a safe and useful antibiotics for the treatment of bacterial infections in pediatric patients. PMID- 1289582 TI - [Clinical studies on cefprozil granules]. AB - Cefprozil granule preparation was administered orally to 16 patients (ages ranging 8 months to 9 years and 6 months) with pediatric bacterial infections at daily dose levels between 29.4 and 35.7 mg/kg divided into 3 or 4 doses. The following results were obtained. 1. Sixteen patients including 5 with pharyngitis, 3 with tonsillitis, 3 with lacunar tonsillitis, 2 with pneumonia, 2 with contagious impetigo and 1 with scarlet fever were treated. Clinical effects were excellent in 9 cases and moderate in 7, with an overall efficacy rate of 100%. 2. Organisms suspected as pathogens included 17 strains (10 strains of haemophilus influenzae, 2 of Haemophilus parainfluenzae, 3 of Streptococcus pyogenes and 2 of Staphylococcus aureus). Bacteriologically, eradication of pathogens were observed for 11 strains, but no changes were obtained for 5 (all Haemophilus), and unknown results were obtained for 1, thus the eradication rate was 68.8%. 3. No side effects were observed. Abnormal laboratory test results included 2 cases of increase in platelets, and 2 of increase in eosinophils, but those were not significant. 4. No refusal of the drug occurred due to its taste or odor. PMID- 1289583 TI - [Clinical studies on cefprozil in pediatrics]. AB - Cefprozil (CFPZ, BMY-28100) fine granules were given orally to 21 children with acute bacterial infections including 15 cases of acute tonsillitis and 3 each of acute bronchitis and urinary tract infections. Good to excellent clinical responses were obtained in 19 of the 21 patients and bacterial eradications were obtained for all 11 strains found in these cases. Loose stool and eosinophilia were observed in 1 case each. From the above clinical results, it appears that CFPZ is a useful antibiotic for the treatment of pediatric patients with various bacterial infections. PMID- 1289584 TI - [Clinical evaluation of cefprozil granules in pediatric field]. AB - Cefprozil (CFPZ, BMY-28100) granules were administered to 20 children with bacterial infections: acute tonsillitis 8, acute bronchitis 10, purulent lymphadenitis 1, urinary tract infection 1. Daily doses ranged 29-50 mg/kg. The drug was given orally, 3 times a day and the durations of administration were 5 to 9 days. Clinical efficacies were excellent in 16 cases and good in 4 cases, hence the overall efficacy rate was 100%. No side effects were observed in any of these cases. As for abnormal laboratory test values, thrombocytosis was observed in 1 case. From the above results, we consider CFPZ granules to be a useful drug for the treatment of pediatric patients with various bacterial infections. PMID- 1289585 TI - [Clinical study on cefprozil fine granules]. AB - Cefprozil (CFPZ, BMY-28100), a new non-ester cephem, was administered to 15 pediatric patients with infectious diseases. The patients included 6 boys and 9 girls from 10 months to 11 years old and they were given oral doses of 18.5-41.7 mg/kg/day for 3 to 8 days. Clinical efficacies were excellent in 3 cases and good in 12 cases, hence the total efficacy rate was 100%. Eosinophilia occurred in 1 case as side effect of the drug, but no other side effects were not found during or after the treatment. PMID- 1289586 TI - [Basic and clinical studies on cefprozil in pediatrics]. AB - 1. Serum levels of cefprozil (CFPZ, BMY-28100) after single oral administration of 7.5 mg/kg were 2.9-5.5 micrograms/ml at 1 hour and trace at 6 hours. 2. Urinary excretion rates of CFPZ were 45.7-102.3% within 6 hours (HPLC). 3. CFPZ was administered at doses ranging 19-47.3 mg/kg/day to 17 cases of pediatric infections including 16 cases with respiratory infections and 1 case with external otitis. Good clinical and bacteriological responses were obtained in all cases. 4. As side effect, diarrhea was observed in 1 case. As abnormal laboratory test results, eosinophilia was observed in 5 cases. PMID- 1289587 TI - [Therapeutic effects of cefprozil in the treatment of various infectious diseases in children]. AB - Therapeutic effects of cefprozil (CFPZ, BMY-28100), a new cephalosporin, were examined in various infectious diseases in children. Clinical efficacy rates were 50% (2/4) in acute bronchitis, 80% (4/5) in pharyngitis, 0% in laryngitis, 100% (7/7) in tonsillitis, 100% (8/8) in impetigo contagiosa, furuncle and posthitis. Hence, the overall efficacy rate was 84% (21/25). Adverse effects were observed in 1 case with slightly elevated serum GOT and GPT. Changes in serum concentrations and urinary excretion of CFPZ were examined in 4 and 2 children without infection, respectively. T 1/2 values obtained were between 1 hour to 2 hours (bioassay). Six hour recovery rates in urine were 51.8% and 77.8% (bioassay). CFPZ was considered to be a safe and useful drug in treating various infectious diseases in children. PMID- 1289588 TI - [Clinical studies on cefprozil granules in pediatric skin soft tissues infections]. AB - Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1289589 TI - [Pharmacokinetic and clinical studies on cefprozil granules in the pediatric field]. AB - Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-positive cocci (GPC) including 2 strains of Staphylococcus aureus, 49 strains of Streptococcus pyogenes, 4 strains of Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of Haemophilus influenzae, 18 strains of Escherichia coli, and 1 strain of Proteus mirabilis. MIC determination of these strains was done with an inoculum size of 10(6) CFU/ml. In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC). CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months. Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively. In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months. A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t.i.d. and 30 cases of q.i.d.) was administered for an average of 7 days. The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis. Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy. The results obtained are summarized as follows: 1. With regard to GPC, MICs of CFPZ against 2 strains of S. aureus were 0.78 or 1.56 micrograms/ml and CFPZ showed the second highest activity to MCIPC. MICs of CFPZ against 49 strains of S. pyogenes were all less than 0.025 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1289590 TI - [Pharmacokinetic and clinical studies of cefprozil fine granules in children]. AB - Cefprozil (CFPZ, BMY-28100) is a new oral cephem antibiotic without an ester linkage. Pharmacokinetic and clinical studies using CFPZ 10% fine granules were performed in pediatric patients. 1. Pharmacokinetic investigation Peak serum concentrations of CFPZ after dose of 7.5 mg/kg and 10 mg/kg were, respectively, 3.65 +/- 0.24 micrograms/ml and 6.38 +/- 3.23 micrograms/ml at 1-2 hours. The average half-life with 7.5 mg/kg administration was 0.90 +/- 0.16 hours and that with 10 mg/kg was 1.29 +/- 0.50 hours. The urinary excretion of CFPZ was about 45% (35.3-50.0%) in 6 hours. 2. Clinical investigation Enrolled in the study were 22 patients including 4 with pharyngitis, 3 with tonsillitis, 3 with bronchitis, 5 with pneumonia, 4 with urinary tract infection, and 1 each with pertussis, purulent lymphadenitis and otitis media. Responses were excellent in 14 patients, good in 5 patients and fair in 1 patient. In the assessment of the bacteriological efficacy, 8 out of 17 strains of organism identified previous to the treatment were eradicated, 5 strains were found replaced by other bacteria and 4 strains persisted, hence the eradication rate was 76.5%. 3. No adverse reactions attributable to the drug were observed. From the above results, it has been concluded that CFPZ is a highly effective and safe agent for moderate respiratory and urinary tract infections in children. PMID- 1289591 TI - The relationship between mitral valve prolapse and acute rheumatic fever in pediatric patients. AB - Mitral valve prolapse (MVP) is a clinical syndrome of which mitral regurgitation and congestive heart failure are the late sequelae. It can be usually diagnosed by echocardiography. In this study, we reevaluated the patients with acute rheumatic fever (ARF) who were followed-up regularly for aspects of MVP. Physical examination, echocardiography and Doppler study were performed for all the patients. One hundred twenty-seven cases of polyarthritis (54.7%), and 105 cases of valvular involvement (45.3%) were diagnosed. Echocardiography demonstrated MVP in 46.8% with isolated mitral insufficiency, in 38.2% with combined valvular defect and in 12.6% with only polyarthritis. One hundred healthy children comprised the control group. Statistical analyses revealed a significant difference in favor of valvular involvement between the groups. PMID- 1289592 TI - Doppler assessment of left ventricular diastolic filling pattern during the convalescent stage of acute myocardial infarction. Effects of infarct size and coronary thrombolysis. AB - Pulsed Doppler echocardiography was used to study left ventricular diastolic filling pattern (LVDFP) over the convalescent stage of acute myocardial infarction (AMI) in 25 patients. Twelve normal subjects served as a control group. The patients were divided on the basis of enzymatically estimated infarct size into 2 groups: 7 as the large AMI group, and the other 18 as the small AMI group. Peak early diastolic filling velocity (E) and the ratio of E to peak filling velocity at atrial contraction (E/A ratio) were determined from the Doppler transmitral flow velocity recordings at 1 and 4 weeks after the onset of AMI. At 1 week E and E/A ratio were significantly lower in the small AMI group compared to the control and the large AMI groups, however, there was no significant difference in E and E/A ratio between the control and the large AMI groups. E/A increased with cumulative CK release among the patients (r = 0.54, p < 0.01). In the following 3 weeks E and E/A ratio decreased only in the large AMI group, and E and E/A ratio at 4 weeks weakly correlated with pulmonary capillary wedge pressure (r = 0.63, p < 0.01 and r = 0.65, p < 0.01) and ejection fraction (r = 0.50, p < 0.05 and r = 0.62, p < 0.01) among the patients. There was no significant difference in E or E/A ratio between patients with and without coronary thrombolysis. Thus, LVDFP in the early convalescent stage of AMI was characterized by low E and E/A ratio in patients with small AMI, however, a "pseudonormalized" pattern was observed in patients with large AMI. The effect of the infarct size on LVDFP diminished in the late convalescent stage of AMI. LVDFP in patients with AMI appears to be influenced by the infarct size and by the time of study. The effect of coronary thrombolysis on LVDFP was not evident throughout the convalescent stage of AMI in this study. PMID- 1289593 TI - Determinants of subsequent late postoperative left ventricular function and reversal of ventricular dilatation after mitral valve replacement for chronic mitral regurgitation. AB - We studied 16 patients with chronic mitral regurgitation by echocardiography before, and at 3 weeks, at 6-8 months and at 1-9 years after mitral valve replacement (MVR) to investigate serial changes in left ventricular (LV) function and reversal of ventricular dilatation. All patients at an average of 2.6 years after, and 8 patients before MVR were also studied by echocardiography and, except for 3 patients by measuring plasma catecholamines from the right atrium during bicycle exercise. Before operation, all patients were divided into group A (n = 12) with end-systolic dimension (ESD) < 4 cm and systolic blood pressure (SBP)/ESD > 3, and group B (n = 4) with ESD > 4 cm and SBP/ESD < 3. Maximum reduction in end-diastolic dimension (EDD) occurred at 3 weeks in all patients after MVR (from 60.5 +/- 3.7 to 49.0 +/- 4.5 mm, p < 0.05). ESD was reduced significantly (p < 0.5) only in group A. LV function was normal in group A, but it was depressed in group B at early and late periods after MVR. The slopes of the relationship between the mean velocity of circumferential fiber shortening (Vcf) and plasma norepinephrine (NE) during exercise in all patients in group B decreased along with the depression in LV function. After operation, all patients in group A reached New York Heart Association (NYHA) functional class I, while patients in group B were in NYHA class II. It is concluded that the surgical outcome after MVR for chronic MR will be better if preoperative ESD < 4 cm and SBP/ESD > 3. The relationship between mean Vcf and plasma NE during exercise seemed to be a useful index to evaluate the inotropic reserve of the LV. PMID- 1289594 TI - Plasma atrial natriuretic factor in patients with acute myocardial infarction. AB - To examine whether atrial natriuretic factor (ANF) is secreted adequately in the early phase of myocardial infarction, plasma ANF concentration and clinical parameters, including hemodynamic variables, were studied in 118 patients with acute myocardial infarction (AMI). The patients were divided into 2 subgroups according to the absence (group A, n = 41) or presence (group B, n = 77) of a history of valvular heart disease, previous myocardial infarction, hypertension, or renal failure. Although no significant difference in atrial pressure after the infarction was found between the 2 groups, the plasma ANF level was significantly lower in group A than in group B (76 +/- 6 vs. 185 +/- 26 pg/ml; mean +/- SEM, p < 0.01). Plasma ANF was correlated with pulmonary capillary wedge pressure in group B (r = 0.54, p < 0.001), whereas no relationship with hemodynamic parameters was observed in group A. In 56 of the 118 patients (group A, n = 18; group B, n = 38), the pulmonary arterial plasma level was significantly higher in group A (p < 0.05), whereas the difference was not significant in group B. Seven of the 8 expired cases among these 56 patients had peripheral plasma ANF levels of more than 150 pg/ml, which were higher than those in pulmonary arterial plasma. These observations suggest firstly that the plasma level of ANF is lower in patients with a new onset of myocardial infarction compared to those with a history of cardiac or renal diseases, and secondly that stimulated ANF release originates not only from the right side of the heart, but also from additional site(s), particularly in patients with chronic ventricle overload and a poor prognosis. PMID- 1289595 TI - Accuracy and reliability of quantitative measurement of coronary arterial stenosis by videodensitometry on coronary angiogram. AB - This study was undertaken to investigate the accuracy and reliability of videodensitometry (VDM) in measuring the magnitude of coronary arterial stenosis on coronary angiogram (CAG). CAG taken after administration of sublingual nitroglycerin was analyzed with VDM (XR-70 Coronary Analyzer, Vanguard). The magnitude of stenosis in coronary segments with four different classes of stenosis was consecutively measured 10 times by the same observer, and the values were 89.0 +/- 1.4, 70.9 +/- 2.1, 59.5 +/- 2.5, and 22.8 +/- 3.4%. The coefficients of variation (CVs), indicating intraobserver variability, were low for severe to moderate lesions (1.6, 2.9, and 4.3%, respectively), but was higher for low-grade lesions (14.8%). When the same lesions were measured by 2 observers, the measurements were highly correlated (r = 0.971, p < 0.01). The results of VDM were consistent with those of conventional gross examination for moderate to severe lesions, and the discrepancy was mainly found in low-grade lesions. The magnitude of stenosis of the same lesion was measured from the right and the left anterior oblique views, and the cineangle was found not to affect the results of VDM. Moreover, cardiac cycle did not affect the videodensitometric measurements of % area stenosis. In order to further investigate the accuracy of VDM, the magnitude of stenosis was measured in nine phantom arteries, and the value measured by VDM significantly correlated with the actual stenosis (r = 0.969, p < 0.001). These results indicate that the values of coronary arterial stenosis on CAG measured by VDM are accurate and clinically acceptable, even though variability is somewhat high for low grade lesions. VDM may be useful for evaluation of the outcome of PTCA and the anti-atherogenic action of some agents. PMID- 1289596 TI - Clinical significance of residual collaterals immediately after successful coronary angioplasty. AB - The clinical significance of collaterals visible on angiography immediately after successful percutaneous transluminal coronary angioplasty (PTCA) was analyzed in 221 patients who underwent successful PTCA for coronary arteries receiving collaterals. Filling of the collaterals was classified as good; filling the entire epicardial segment of the stenosed site, fair; partially filling the epicardial segments distal to the stenosed site, and faint; visible but not filling the epicardial segments of the diseased vessel. Fifteen of 41 good collaterals remained good or fair on angiography immediately after PTCA. Among the 114 fair collaterals, 26 remained fair and 20 of 66 faint collaterals remained visible on the angiogram immediately after PTCA. There was no relationship between the degree of residual stenosis after PTCA and the degree of residual collaterals. Repeat coronary angiography was obtained in 156 patients. There was no correlation between the presence, absence or degree of collaterals observed on angiography immediately after successful PTCA and the rate of restenosis. Thus, collaterals to the vessels dilated by PTCA often remain on the angiogram immediately after PTCA and are dependent primarily on their degree before dilation. They do not indicate inadequate dilation or predict restenosis. PMID- 1289597 TI - High prevalence of coronary artery spasm in survivors of cardiac arrest with no apparent heart disease. AB - The pathogenesis of cardiac arrest in the absence of any apparent heart disease remains unclear. Based on the hypothesis that coronary spasm may be a cause of cardiac arrest in the absence of apparent heart disease, ergonovine testing and/or electrophysiologic studies (EPS) were performed to evaluate the cause of cardiac arrest. Fourteen patients resuscitated from cardiac arrest had no apparent heart disease. A spontaneous episode of angina with ST-segment elevation occurred in 4 patients while under observation. Ergonovine testing was performed in 9 patients, and coronary spasm was induced in 5. EPS were performed in 8 patients, including 3 patients with coronary spasm. No electrophysiologic abnormalities were found in the 3 patients with coronary spasm. Ventricular fibrillation was induced by programmed ventricular stimulation in 2 patients with documented ventricular fibrillation at the time of resuscitation. All but one of the patients with coronary spasm had chest pain preceding cardiac arrest or at least a history of chest pain at rest, while 4 of 5 patients without coronary spasm had no prodromal symptoms. Patients with coronary spasm had a good prognosis when treated with a Ca-antagonist and/or long-acting nitrate. In conclusion, coronary spasm is the most frequent cause of cardiac arrest in cardiac arrest survivors with no apparent heart disease. Ergonovine testing should be performed to evaluate the cause of cardiac arrest when patients have no apparent heart disease. PMID- 1289598 TI - Effect of anoxic preperfusion on ischemic myocardial injury in isolated rat hearts. AB - Anoxic perfusion prior to sustained ischemia (anoxic preperfusion), reportedly improves postischemic functional recovery of the heart, but its mechanism has not been well understood. The present study aimed to characterize the cardioprotective effects of anoxic preperfusion and its relationship to extracellular Ca++ levels. Following 10 min of aerobic perfusion, isolated rat hearts were assigned to a 10 min aerobic perfusion or to a 10 min anoxic perfusion. The hearts were then subjected to 30 min of global ischemia and 30 min of aerobic reperfusion. When the perfusate-free Ca++ concentration was 2.0 mM, postischemic recovery of left ventricular developed pressure was significantly improved by anoxic preperfusion (91.9 +/- 2.9% of baseline value vs. 50.5 +/- 12.9% after 30 min reperfusion in the controls). However, the improvement of postischemic ventricular function by anoxic preperfusion was abolished when perfusate Ca++ was reduced to 1.0 mM and the contractile function was rather suppressed during early reperfusion by anoxic preperfusion when the Ca++ level was 0.7 mM (87.5 +/- 11.8% vs. 115.6 +/- 13.9% after 10 min of reperfusion). On the other hand, lactate accumulation during the global ischemia was significantly less in anoxic preperfused hearts compared with untreated hearts both when perfusate Ca++ was 0.7 mM (61.3 +/- 5.1 vs. 85.9 +/- 6.8 mumol/g dry) and when it was 2.0 mM (43.8 +/- 2.0 vs. 140.3 +/- 14.1 mumol/g dry). The amount of myoglobin released after global ischemia was not different between untreated and anoxic preperfused hearts regardless of the perfusate Ca++ level. The results suggest that anoxic preperfusion does not reduce ischemic myocardial necrosis, but it attenuates myocardial stunning. That effect of anoxic preperfusion on the stunning is dependent on the extracellular Ca++ level and is not totally explained by suppression of ischemia-induced lactate accumulation. PMID- 1289599 TI - Effect of L-carnitine on the cellular distribution of carnitine and its acyl derivatives in the ischemic heart. AB - The purpose of this study was to investigate the cellular distribution of carnitine and its acyl derivatives in the normal and ischemic myocardium, and the effects of exogenous 1-carnitine on this distribution and mitochondrial function in the ischemic dog heart. Under non-ischemic conditions, about 93% of the total cellular carnitine was located in the cytosolic compartment and 6.5% in the mitochondrial compartment. Sixty minutes of ischemia induced a decrease in the cytosolic free carnitine content, but caused the accumulation of long-chain acylcarnitine in the cytosolic and mitochondrial compartments. Treatment with 1 carnitine (30 or 100 mg/kg, i.v.) inhibited the mitochondrial accumulation of long-chain acylcarnitine. Free fatty acid (FFA) metabolism in the mitochondria differs from that in the cytosol. So, it is necessary to investigate the changes in FFA metabolism in both of these cellular compartments. Our results suggest that 1-carnitine has a protective effect on the ischemic heart by selectively reducing mitochondrial accumulation of long-chain acylcarnitine. PMID- 1289600 TI - The role of calcium activated neutral protease on myocardial cell injury in hypoxia. AB - The aim of this study was to investigate the correlation between hypoxic myocardial cell injury and intracellular protease activity. Cardiac myocytes were isolated from neonatal rat hearts and cultured in Eagle's modified minimum essential medium. Myocytes were incubated in hypoxic conditions for 6 hours. The cell death rate during hypoxia rose to 80% after 6 hours. Extracellular protease activity was elevated to 4 units during hypoxia, much higher than the 0.7 units in aerobic states at 6 hours. This extracellular protease activity in hypoxic conditions was markedly inhibited by leupeptin and EDTA, and weakly inhibited by the cysteine protease inhibitor, NCO-700, but phenylmethyl sulfonyl fluoride did not inhibit the protease activity. To identify the protease activated during hypoxia, calpain-specific inhibitors were added to the incubation mixture. Calpain inhibitor 1 and calpastatin, an endogenous selective calpain inhibitor, markedly inhibited extracellular protease activity during hypoxia. NCO-700 also inhibited intracellular protease activity. NCO-700 reduced hypoxic cell death to 30% after 6 hours of hypoxygenation. These observations indicate that calpain is activated during hypoxia and leads to irreversible cell membrane degradation after 6 hours of hypoxygenation. PMID- 1289601 TI - Histochemical study of calmodulin in dog myocardial ischemia and sudden cardiac death. AB - The distribution of calmodulin was investigated in dog myocardium after coronary artery occlusion by an immunoperoxidase technic and compared with the distribution of myoglobin and the findings of hematoxylin-eosin (H-E) staining. After 60 min or more of coronary artery ligation, calmodulin diffused clearly from myocardium in the region of hypereosinophilia (H-E) or stained intensely in regions of a contraction band or hydropic appearance. Similar findings were observed in the myocardium of cases of sudden cardiac death. The intense staining for calmodulin would reflect the association of calmodulin with membranes in response to the calcium overload that plays an important role in myocardial injury. Calmodulin staining provided more information than myoglobin staining, which only detected diffusion from necrotic cells. This method would be useful to elucidate the implications of calcium and calmodulin during the development of myocardial injury. PMID- 1289602 TI - Torsade de pointes induced by hypocalcemia in a postoperative patient with thyrotoxicosis. AB - A 29-year-old woman with a long-term history of Graves' disease was admitted for thyroidectomy. Torsade de pointes occurred after the subtotal thyroidectomy. The level of her serum calcium was lower than normal. After administration of calcium gluconate intravenously, torsade de pointes disappeared and was no longer recorded. It is assumed that her torsade de pointes was caused by hypocalcemia as a complication of subtotal thyroidectomy. PMID- 1289603 TI - [Analysis of the electrical charge of albumin in idiopathic nephrotic syndrome by isoelectric focusing]. AB - The state of the electrical charge of serum and urinary albumin was investigated in both the nephrotic and remission stage of idiopathic nephrotic syndrome (INS), using isoelectric focusing (IEF). 1) Both a b2 band (a main albumin band appearing at the site of isoelectric point: pI 4.7), and a b3 band (a more anionic albumin band than the b2 band) were detected commonly in all samples of urine and serum of INS patients in nephrotic and remission stages and of healthy volunteer controls even if the applied albumin in urine and serum amounted to 20 micrograms or 100 micrograms. 2) When applied albumin amounted to 20 micrograms, b1 bands (less anionic albumin bands than the b2 band) were detected between pI 4.7 and pI 6.5 in urine and in both serum and purified albumin fractionated from serum of INS patients in the nephrotic stage. However, b1 bands were not detected at all in the urine and serum of either INS patients in remission stage and healthy volunteer controls. 3) When applied albumin amounted to 100 micrograms, b1 bands were detected also in serum of healthy volunteer controls. From these results, it was confirmed that less anionic albumin existed also in the serum of healthy volunteer controls although the amount was extremely small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289604 TI - [Cu, Zn-superoxide dismutase, glutathione peroxidase location in kidney of IgA nephropathy]. AB - To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in glomeruli of patients with IgA nephropathy by immunohistochemical method. Thirty three kidney specimens were used consisting of 28 IgA nephropathy and, normal parts of the 5 resected kidneys with renal tumors as controls. To evaluate the change of renal function and renal histological grade, creatine clearance (Ccr) and histological grade were assessed at the time of biopsy. In normal kidney, Cu, Zn-SOD and GSH-Px was localized in tubular cells, and not in glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD and GSH-Px were detected in epithelial side of the glomerular capillary wall in addition to the tubular cells. The positive correlation was observed between the glomerular localization of Cu, Zn-SOD and that of GSH-Px. As for the relation between the extent of localization of these enzymes and clinical findings at the time of biopsy, the following results was obtained. When Cu, Zn-SOD and GSH-Px was strongly stained in glomeruli, histological change of glomeruli was milder. These results suggest that Cu, Zn-SOD and GSH-Px have the beneficial actions for renal function as anti-oxidative factors. PMID- 1289605 TI - [Effect of oral adsorbent (AST-120) in the rat model of chronic renal failure induced by adriamycin]. AB - The effect of AST-120 was examined in the rat model of CRF induced by adriamycin (ADM), which is known to induce focal glomerular sclerosis (GS). ADM (2mg/kg) was injected intravenously twice at a 3-wk interval. After 14 wks, rats were paired with control (C) and AST-120 (A) groups according to levels of BUN and proteinuria. Then, the rats were fed regular rat chow with (A, n = 10) or without (C, n = 10) AST-120. After 28 wks, there were more GS in C. Averaged sclerosis index (SI, 0-4 scale) in C was 1.97 (0.94-3.22), while 1.61 (0.60-2.97) in A. When GS was advanced in C (SI > 2.0), largely ameliorated SI was noted in A (2.61 vs. 1.97, C vs. A, p < 0.05 by paired W-test, n = 5 each). Also, in these rats, BUN, serum creatinine and Ht were all improved in A (p < 0.05). Thus, AST-120 was effective in CRF rats induced by ADM when uremia was advanced. The data also indicates that a reduction of uremic toxins could improve glomerular histology and renal function in CRF. PMID- 1289606 TI - [Alterations of gluconeogenesis by ischemic renal injury in rats]. AB - This study was designed to determine changes in one of metabolic functions, gluconeogenesis after ischemic renal injury. Right kidneys of SD rats were removed and a vascular clamp was placed across the left renal artery and vein for 0, 10, 30, 60 and 90 min. On 1, 3 and 7 days after the treatment, tubule suspensions were prepared by collagenase treatment of left kidneys and incubated with or without 2 mM pyruvate or malate aerobically. After the incubation, glucose contents were assayed photometrically. Serum creatinine was also determined. In addition, morphological changes were observed under light microscopy to examine the relationship between metabolism and morphology. The tendency of increase of gluconeogenesis was observed on day 1 and 3 after 10, 30, 60 min of ischemic time. On the other hand, gluco-neogenesis decreased significantly on day 1 after 90 min treatment. In contrast, on day 1 and 3 after treatment, serum creatinine levels showed no difference from control at the groups of 10 and 30 min ischemia. Whereas it rose significantly at the group of 60 min ischemia, showing a different tendency from that of the increase of gluconeogenesis. Moreover, morphologic damage was observed on day 1 and 3 after ischemia of 30 and 60 min. The morphologic damage was found more advanced in the corticomedullary region than those of the cortex which has the high gluconeogenic activity and which thus showed relatively limited damage. These results suggest that renal gluconeogenesis is relatively insusceptible to ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289607 TI - [Effects of age, renal diseases and diabetes mellitus on the renal size reduction accompanied by the decrease of renal function]. AB - Renal size reduction accompanied by the decrease of renal function was evaluated by ultrasonography in 30 normal controls, 45 patients with chronic renal diseases (CRD) and 22 patients with diabetic nephropathy (DN). In controls, significant positive correlation was observed between sectional areas of right kidney and creatinine clearance (Ccr) (r = 0.794, p < 0.001), suggesting that the decrease of renal function due to aging was accompanied by the renal size reduction. Significant correlation was also found between the size and Ccr in CRD (r = 0.814, p < 0.001) and DN (r = 0.640, p < 0.01). No significant difference was observed between controls and CRD in the reduction rate of renal size per unit change of Ccr, which suggested that the renal size reduction accompanied by the decrease in Ccr was the same in controls and CRD. In contrast, in DN, renal size reduction accompanied by the decrease in Ccr was smaller than controls or CRD. When renal sizes were compared in patients, whose Ccr were equal or less than 20 ml/min, renal sizes were significantly larger in DN than CRD (p < 0.001). The duration of illness from the onset of proteinuria was longer in CRD than DN (13.5 years and 4.7 years, respectively). The difference of renal sizes, however, can not be fully explained by the differences in the length of illness, since the renal size was larger in DN than CRD even when we compared the patients with the similar length of illness. In conclusion, renal size decreased with the reduction in the renal function in controls, CRD and DN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289608 TI - [Guanidino compounds and aliphatic monoamines in acute and chronic renal failure]. AB - Small molecular weight uremic toxins, guanidino compounds and aliphatic monoamines, were measured in the serum of chronic and acute renal failure (CRF and ARF) patients. A close correlation was noticed between guanidinosuccinic acid (GSA) and serum urea nitrogen (BUN) and also between methylguanidine and serum creatinine (Cr) in nondialyzed and dialyzed CRF patients. The same relation was seen in ARF patients showing rapid change of metabolic conditions, which suggested the tight linkage between guanidino compounds and protein metabolites. On the other hand, dimethylamine (DMA) was related with Cr in CRF patients, however, not in ARF patients. Since the production of DMA from Cr is carried out mainly, but relatively slowly, by bacterias in the intestine, the rapid metabolic change of ARF may not affect DMA synthesis. Furthermore, the DMA synthesis from trimethylamine-N-oxide (TMA-N-O) was studied using liver homogenate. The liver homogenate produced DMA by adding TMA-N-O as substrate. However, the kidney homogenate could synthesize it even without substrate. Therefore, the kidney seems to be a major site of DMA production as well as the intestine. PMID- 1289609 TI - [MCNS, which secondary developed into incidental IgA nephropathy--a case report]. AB - There have been a number of case reports on nephrotic syndrome with histological findings of minimal change on light microscopy and mesangial IgA deposition on fluorescent microscopy. The pathogenesis of these cases is, however, yet to be clarified. Here, we report a case of minimal change nephrotic syndrome (MCNS) associated with IgA nephropathy, which developed later in the course of MCNS. The patient was 18 years old male with steroid-responsive nephrotic syndrome. First episode of proteinuria occurred when he was 4 years old. On the fourth episode of proteinuria, renal biopsy revealed minimal change on light microscopy and no evidence of deposition of immunoglobulins or complements on immunofluorescent and electron microscopy. On the fifth relapse of MCNS, microhematuria developed concomitantly with massive proteinuria. Renal biopsy, then, showed light microscopic findings of mild focal segmental glomurulonephritis. Significant mesangial IgA deposition was observed on immunofluorescence study. Electron microscopy revealed electron dense deposit in the mesangial and paramesangial area. The patient was well-responsive to steroid although microhematuria persisted after disappearance of proteinuria. We concluded that IgA nephropathy may have developed subsequently in the course of MCNS in our case. PMID- 1289610 TI - [A case report of chronic tubulo-interstitial nephritis]. AB - We report a case of 10-year-old boy with chronic tubulo-interstitial nephritis (TIN). He had febrile convulsion and received sodium valproate (VPA) treatment. 18 months later, he had developed Fanconi syndrome. On admission, he also had evidence of tubular and glomerular dysfunction. Renal biopsy revealed interstitial nephritis with linear tubular-basement-membrane deposition of IgG and C3 and dominant infiltration of CD4 positive cells in interstitium. Although there is not a positive proof of the etiology in the relationship between TIN and VPA, it is likely that VPA is a possible cause of chronic TIN from his past history. PMID- 1289611 TI - [Tissue renin content in superficial, midcortical, and juxtamedullary afferent arterioles in rabbits]. AB - Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity. PMID- 1289612 TI - [Renin release from microdissected superficial, midcortical, and juxtamedullary afferent arterioles in rabbits]. AB - Though renin release from a single superficial afferent arteriole has been studied extensively, there is no report on renin release from a single midcortical or juxtamedullary afferent arteriole. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined renin release from a single afferent arteriole. In result, we got the following conclusions. 1. Basal renin release per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles during both normal and low sodium intake. 2. Isoproterenol (1.6 x 10(-4)M) significantly stimulates renin release from all three types of arterioles on either diet; however, only in the superficial arterioles is the increase (delta) greater with dietary sodium restriction. These findings indicate substantial heterogeneity of basal and isoproterenol-stimulated renin release, and response to chronic sodium depletion. PMID- 1289613 TI - Cortical area related to lens accommodation in cat. AB - Lens accommodation was evoked by microstimulation in the lateral suprasylvian (LS) area in cats. The accommodative response was monitored continuously with an infrared optometer. The low threshold areas related to lens accommodation were located in the lower parts of the medial banks of the middle suprasylvian sulcus from A1 to A4, and also in the fundus of the sulcus at A8 in the stereotaxic coordinates. The latency of the onset of the accommodative responses evoked by stimulating the caudal area (A1-A4) was shorter than that evoked by stimulating the rostral area (around A8). Electrical stimulation was also attempted at the subcortical area in order to study the output pathway from the LS area. It was determined that the low threshold sites in the LS cortex of A1-A4 extend rostrally along the lateral ventricle in the brainstem, then ventrally into the midbrain. These findings suggest that there are two cortical areas related to lens accommodation: caudal and rostral, and the caudal accommodation area may provide the output signal for the subcortical system. PMID- 1289614 TI - Quantitative and morphometric studies of age-related changes in human ciliary muscle. AB - The age-related changes in ciliary muscles were studied morphologically in 20 human eyes ranging from 3 months to 90 years of age. The meridionally cross sectioned area and the volume of ciliary muscles increased with age until 70 years, but then decreased. The circular fiber in the ciliary muscle was undeveloped in the infantile eye. However, it continued to develop until about 70 years of age, and then decreased. The connective tissue in the ciliary muscle showed a proportional age-related increase. Over 71 years of age the proportion of connective tissue became larger than that of the muscle fiber. The number of nuclei in the ciliary muscle was maximum in eyes between 21 to 40 years of age, and subsequently there was a continuous and distinct decrease in the circular fiber with age. The age-related increase of connective tissue and decrease of nuclei in the ciliary muscle together with the decreasing circular fiber suggested a possibility of atrophy in the ciliary muscle with age-related deterioration of accommodation. PMID- 1289615 TI - Histological and histochemical studies on developing ciliary body in eye of ICR mouse. AB - Histological and histochemical studies have been made on the microscopic structures of the ciliary body from the developing eyes of both pre- (on day 13, 16 and 18 of gestation) and postnatal (on day 1, 5, 10, 14 and 84) mice of the Jcl:ICR strain and on the acidic glycoconjugates contained in the ciliary body tissues of these animals. As the staining procedures of choice, a hematoxylin eosin procedure and a sensitized high iron diamine method were employed. A nitrous acid procedure was used in combination for some tissue sections, prior to the sensitized diamine method, to aid in the identification of sulfated glycoconjugates. Both the partes optica and caeca retinae could be identified histochemically as early as day 13 of gestation, whereas these parts could not be histologically distinguished from each other at day 16 of gestation. The ciliary folds were detected first in the external layer at day 16 of gestation and subsequently in the internal layer 2 days later. The heparan sulphate proteoglycan observed not only in the thick basement membrane but also in the intra- and intercellular spaces of the internal layer was localized in a distribution pattern which prevented the occurrence of configurational discrepancies between the epithelial cells lining the layer because of the formation of ciliary folds. PMID- 1289616 TI - Recombinant human epidermal growth factor and corneal neovascularization. AB - With a view toward possible future clinical application, we investigated whether recombinant human epidermal growth factor (hEGF) could induce corneal neovascularization. Ethylene-vinyl-acetate copolymer slow-release pellets containing either 250 ng, 500 ng or 1 microgram of hEGF or 250 ng of bovine serum albumin (BSA) were implanted into rabbit corneal stroma, and the corneas were examined by slitlamp biomicroscope for 3 weeks. The results indicated that less than 1 microgram of hEGF per pellet did not induce neovascularization in the cornea. However, when pellets containing 250 ng of basic fibroblast growth factor (bFGF) were implanted, corneal neovascularization toward these pellets occurred within 10 days. The same phenomenon occurred toward the 250 ng hEGF pellets embedded in the ipsilateral or contralateral cornea of the same animal, but was significantly less severe. When a pellet containing 250 ng bFGF was intramuscularly implanted in the animal's back, similar neovascularization was observed toward the pellets containing hEGF implanted in the same animal's cornea, but not toward implanted pellets containing BSA. These results suggest that less than 1 microgram of hEGF cannot initiate corneal angiogenesis, but can promote new vessel formation if the limbal vasculature is activated by a sprouting signal from a certain substance as trace amounts of bFGF. PMID- 1289617 TI - Keratoepithelioplasty in rat: development of a model and histological study. AB - A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP. PMID- 1289618 TI - Alteration of lens disulfide bonds in newly developed hereditary cataract rat. AB - A newly developed hereditary cataract rat named Shumiya Cataract Rat (SCR) is introduced. The lens opacity manifests spontaneously in the nuclear and perinuclear portions of the lens in this model at 11 weeks of age. Raman optical dissection studies reveal that lens protein disulfide bonds are considerably decreased in the SCR opaque lens nucleus. This tendency is also detected in the precataractous stage. The simultaneous increase of lens protein sulfhydryl groups is observed in the affected lens nucleus. The glutathione disulfide (oxidized glutathione) level, on the contrary, is elevated in the SCR opaque lens, whereas the glutathione sulfhydryl (reduced glutathione) level is decreased. It is suggested that the impaired formation of protein disulfide bonds is related to lens opacification in a hereditary manner. PMID- 1289619 TI - New inferior retinal detachment after scleral buckling procedure with intraocular gas injection. AB - In a series of 72 rhegmatogenous retinal detachments treated by scleral buckling procedure with or without intraocular gas injection, 5 patients showed a subsequent inferior retinal detachment in the operated eye early in the postoperative period. All 5 eyes had been injected with air or sulfur hexafluoride intraoperatively or postoperatively, and had vitreoretinal adhesions such as lattice degeneration in the inferior equatorial fundus. To investigate the factors involved in the development of the new inferior retinal detachment, the data on the 72 eyes of retinal detachment were analyzed. Intraocular gas injection, inferior vitreoretinal adhesion, and the volume of injected gas were the significantly associated factors (P < 0.05). It was suggested the intraocular gas bubble could produce traction on the site of inferior vitreoretinal adhesion, leading to new inferior retinal detachment. PMID- 1289620 TI - Lymphatic sinus-like structures in choroid. AB - Lymphatic sinus-like structures were demonstrated in the choroid of the monkey eye by transmission and scanning electron microscopy. These lymphatic sinus-like structures were lined by fibroblast-like cells with large intercellular gaps. When the specimens were viewed by scanning electron microscopy, the surface morphology of the fibroblast-like cells was similar to that of the endothelial cells of blood vessels or lymphatic vessels. Some fibroblast-like cells possessed intracellular fenestrations which varied in size, number and distribution. It is suggested that the lymphatic sinus-like structures here observed might play a role in the drainage of fluid from the choroid. PMID- 1289621 TI - Immunohistological study of subretinal membranes in age-related macular degeneration. AB - An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors. PMID- 1289622 TI - Intraocular manifestations of systemic sarcoidosis. AB - The incidence of intraocular manifestations was studied in 159 patients with systemic sarcoidosis. Eighty-seven patients (54.7%) who presented ocular lesions suggestive of sarcoidosis as an initial manifestation were diagnosed after a systemic survey. Seventy-two patients (45.3%) had chest signs or symptoms and were referred to ophthalmic examination during a diagnostic survey. Of the 159 patients, 126 (79.2%) showed intraocular involvements at diagnosis. In these patients with ocular involvements, iritis was the most frequent lesion, being seen in 74.7%. Gonioscopic examinations revealed trabecular nodules and tent-like peripheral anterior synechia in 61.2 and 54.5% of the patients respectively. Retinal perivasculitis and spotty retinochoroidal exudates were seen in 67.3 and 53.9% of the patients respectively. The data indicated the presence of intraocular lesions in a significant number of patients with sarcoidosis. These findings emphasize that all patients with systemic sarcoidosis need a thorough eye examination. This ocular examination should include gonioscopy. PMID- 1289623 TI - Molecular basis of congenital color vision defects in Chinese patients. AB - Applying Southern blot hybridization, the structures of the red pigment gene (RPG) and the green pigment gene (GPG) were analyzed in 43 Chinese patients with red-green color vision defects, including 3 female cases of deuteranopia. The same analysis was carried out in 4 normal relatives and 3 carriers from 3 affected families, as well as in 11 normal controls. Among the 43 patients, abnormalities of the RPG were detected in all 19 protans, and abnormalities of the GPG were found in 14 of the 24 deutans. In about 80% of the protans and deutans, an alteration of exon 5 in RPG or GPG was discovered. All 19 protans had anomalous RPG and in one protan the normal RPG was replaced by a 5' red-3' green hybrid gene. However, no protans showed deletion of the whole RPG. Some deutans had no GPG; some had a 5' green-3' red hybrid gene with or without the GPG. The exon 5 of RPG and GPG was amplified by polymerase chain reaction (PCR) and the amplified fragments were further analyzed by RsaI digestion. The results of PCR were identical to those of nucleic acid hybridization. PCR will be a useful tool in prenatal diagnosis and genetic counseling. PMID- 1289624 TI - [Prediction formulas for pulmonary function tests expressed in linear and exponential form for healthy Japanese adults]. AB - We studied 21 parameters of pulmonary function in 172 healthy Japanese adult smokers and non-smokers ranging from 18 to 83 years of age. Prediction formulas for each parameter were calculated in both linear and exponential form using multiple regression analysis with regard to sex, age, height and weight. The exponential form was superior to the linear form for V25, V50, PEF, FVC, VC, FEV1.0, FEV1.0%, TLC, DLCo and DL/VA, namely, the parameters whose predictive value decreases with aging. In particular for V25, only the exponential form of the predictive formula could be applied for subjects with advanced age. For PMI, LCI, IDI, pulmonary N2 clearance delay, and single breath delta N2, indices for unevenness of intrapulmonary gas distribution, there has been no previous report about their predictive formulas and ours is the first. These predictive formulas all showed increasing values with aging, and showed higher predictive values in females than in males, except for delta N2. These parameters require further study with respect to their normal value ranges and differences between males and females. PMID- 1289625 TI - [Elemental analysis of hilar and mediastinal lymph nodes in idiopathic pulmonary fibrosis]. AB - Elemental analysis of hilar and mediastinal lymph node tissues was performed to determine whether some inhaled atmospheric elements are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). IPF was divided into two types; typical and atypical, according to our criteria. Lymph nodes were selected as the study material rather than lung tissue, because inhaled elements are concentrated in the hilar and mediastinal lymph nodes, and increase in lung weight due to fibrosis may influence the estimated values of element per unit weight of lung tissue. The hilar and mediastinal lymph nodes collected from 40 IPF cases and 43 non-IPF control cases were examined to determine the concentration of 13 elements in 100 mg dry tissue, using the X-ray fluorescent analysis method. For aluminium, 50 mg dry tissue was examined by an atomic absorption analysis method. Among the 14 elements, Ni in IPF lymph nodes showed a significantly higher level than in control nodes (mean +/- SD: 8.2 +/- 21.3 ppm versus 1.1 +/- 2.1 ppm, respectively. p < 0.01). No difference in each of the examined elements was noted between smokers and non-smokers or between typical and atypical IPF cases. Exogenous elements such as Ni may play a role as triggering substances in the pathogenesis of IPF. PMID- 1289626 TI - [Effects of respiratory tract infections and antibiotic therapy on NADPH oxidase activity]. AB - The superoxide generation of neutrophil NADPH oxidase was investigated in healthy subjects, patients with respiratory tract infections, and patients receiving effective antibiotic therapy. In adults, oxidase activity significantly increased during respiratory tract infections and decreased after treatment with effective antibiotics. In the elderly, no significant increase in oxidase activity was observed during respiratory tract infections, while the activity significantly decreased after therapy. Increases in white blood cell counts, neutrophil counts and C-reactive protein values in the elderly during respiratory tract infections were less marked than those in adults. These abnormalities in both adults and the elderly were restored to within normal limits after antibiotic therapy. In in vitro experiments, antibiotics, such as imipenem, ceftazidime and cefoperazone, at each therapeutic dose did not inhibit the superoxide generation of NADPH oxidase. These results suggest that in the elderly, defense activity against infections may be suppressed, and that these antibiotics may normalize neutrophil NADPH oxidase activity as a result of their bactericidal action and a possible biological action to normalize the peri-neutrophil environment of the body. PMID- 1289627 TI - [Tumor associated carbohydrate antigens in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis]. AB - It is known that tumor associated carbohydrate antigens are significantly increased in the serum of patients with diffuse panbronchiolitis (DPB). We investigated carbohydrate antigens (SLX, CA19-9) in bronchoalveolar lavage fluid (BALF) obtained from 24 patients with DPB. The concentrations of SLX and CA19-9 were significantly higher in BALF from patients with DPB than those from healthy subjects (7 cases) and patients with pulmonary sarcoidosis (16 cases). No significant correlation was observed between either SLX or CA19-9 concentrations in the serum and BALF, and no significant correlation was observed between the concentrations of these carbohydrate antigens in BALF and clinical findings. Immunohistochemical study of SLX and CA19-9 in open lung biopsy specimens obtained from patients with DPB showed expression of SLX and CA19-9 on the bronchiolar surface epithelial cells and mucinous exudates in air spances. These results indicate that carbohydrate antigens are presumably increased in the pulmonary lesions of patients with DPB, and this increase causes high levels of these antigens in the serum. Furthermore, we investigated the change of concentrations of SLX and CA19-9 in BALF obtained from patients with DPB after erythromycin (EM) treatment. The concentrations of these two antigens were decreased after EM treatment. PMID- 1289628 TI - [Pulmonary function and exercise tolerance in patients treated with bone marrow transplantation (BMT)]. AB - We assessed pulmonary function and exercise tolerance in 10 BMT patients. Their underlying disorders were as follows; chronic myeloid leukemia 5 cases, acute lymphoblastic leukemia 2 cases, aplastic anemia, acute myeloid leukemia and non Hodgkin's lymphoma one case each. Their mean age was 26 +/- 9 years old. When the patients were healthy and free of serious complications and anemia, arterial blood gas examination, pulmonary function tests and incremental treadmill exercise test were examined repeatedly. Although %VC and FEV1.0% kept within normal range, PaO2 at rest, %DLCO, VO2max, VO2max/kg and O2-pulsemax remained low at one year after BMT. There were significant correlations between VO2max and O2 pulsemax [r = 0.955 (p < 0.001)], %VC [r = 0.758 (p < 0.02)], VE/VO2max [r = 0.749 (p < 0.02)] and delta SaO2/VO2/kg [r = -0.731 (p < 0.02)], suggesting that exercise intolerance in BMT patients may be based on both cardiac and gas exchange abnormalities. To evaluate cardiac dysfunction, we compared exercise parameters obtained at an exercise level of 75% predicted heart rate max in five age-matched normal subjects to those in six BMT patients who did not demonstrate desaturation during exercise. As a result, the mean values of VO2max/kg and O2 pulse/m2 in BMT patients were significantly lower than those in normal subjects, suggesting that cardiac dysfunction may be due to insufficiency of stroke volume during exercise. It is concluded that exercise intolerance in BMT patients may be mainly due to cardiac dysfunction. PMID- 1289629 TI - [Serum 7S collagen levels in diffuse interstitial lung diseases--an index of the destruction of alveolar structure]. AB - To examine whether alteration of 7S collagen in the alveolar basement membrane is related to the condition and prognosis of diffuse interstitial lung diseases (idiopathic interstitial pneumonia: IIP, collagen vascular diseases, sarcoidosis, and hypersensitivity pneumonitis), we measured serum 7S collagen levels in 123 patients with diffuse interstitial lung disease and other lung diseases. Patients with diffuse lung diseases (diffuse interstitial lung disease, pulmonary emphysema, and diffuse panbronchiolitis: DPB) showed significantly higher serum levels of 7S collagen than healthy normal controls. Serum 7S collagen levels in IIP and collagen vascular diseases were significantly higher than those in pulmonary emphysema and DPB. In cases of IIP, serum 7S collagen levels in the active stage were significantly higher than those in the inactive stage. Furthermore, the prognosis of patients with higher serum 7S collagen levels was significantly poorer than those of patients with lower serum 7S collagen levels. In infectious pulmonary diseases, serum 7S collagen levels of patients with adult respiratory distress syndrome (ARDS) were significantly higher than those of patients without ARDS. Autopsy specimens obtained from patients with positive serum 7S collagen showed diffuse alveolar damage and/or diffuse pulmonary hemorrhage in the alveolar areas. Immunohistochemical staining for 7S collagen showed disruption and/or loss of the alveolar basement membrane. The authors conclude that serum level of 7S collagen is useful for estimating the activity of diffuse interstitial lung diseases as an index of the destruction of alveolar structure. PMID- 1289630 TI - [Alteration of oxygen extraction and blood flow in various organs under acute hypoxia]. AB - To assess the compensatory mechanisms involved in maintaining aerobic metabolism in various organs during exposure to acute hypoxia, five anesthetized and paralyzed dogs were ventilated with either normoxic (FIO2: 0.21) or hypoxic gas mixture (FIO2: 0.13). Under both conditions, we examined systemic and pulmonary hemodynamic parameters, and took samples of arterial and mixed venous blood as well as venous blood from various organs including the heart, brain splanchic organs (hepatic vein) and kidney. Based on PO2, PCO2 and pH values as measured with electrodes, we calculated O2 and CO2 contents in each blood sample. The values thus obtained were then used to estimate the O2 extraction ratio (ER), gas exchange ratio (R) and difference of base excess between arterial and venous blood (avBE) in the whole body as well as in each organ. In addition, both O2 delivery (DO2) and O2 consumption (VO2) in the whole body were calculated. Although the whole body showed a decrease in DO2 and an increase in ER during hypoxic gas breathing, other parameters including R, avBE and VO2 did not change significantly. Higher ER values were found in the heart and brain than those in the splanchic organs and kidney, the qualitative trend being the same irrespective of FIO2. On the other hand, increase in ER during hypoxic gas breathing was considerably larger in the splanchic organs and kidney than that in the heart and brain. There was no significant difference in R and avBE in any of the organs between normoxic and hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289631 TI - [Clinical study on benefit and safety of frequent inhalation of aerosolized procaterol hydrochloride in aged acute asthmatics]. AB - We studied the hemodynamic effects of frequent inhalation of aerosolized procaterol hydrochloride (PRC) in the treatment of status asthmaticus. Twenty patients were enrolled and divided into 2 groups; younger group (less than 55 years; n = 11) and older group (more than 55 years; n = 9). All patients were treated with intravenous hydrocortisone (4 mg/kg/4 h) and PRC inhalation (30 micrograms; 0.3 ml) every hour via a jet nebulizer with 3 l/min oxygen for four consecutive days. Holter ECG monitoring was performed on the 1st, 4th, and 7th days of hospitalization to evaluate mean heart rate, tachycardiac incidence, and arrhythmias. Blood pressure, serum potassium levels, and peak expiratory flow rate (PEFR) were measured on the same day. Even though the total dosage of inhaled PRC on the 1st day was 496.4 +/- 62.61 micrograms for the younger group and 490.0 +/- 36.73 micrograms for the older group (p = NS), total arrhythmic ratios were less than 1% in both group. Both blood pressure and heart rate decreased with improvement of symptoms and PEFR value. Serum potassium levels tended to decline according to the administered dosage of PRC (p < 0.01); however, severe hypokalemia less than 3.0 mmol/l was not observed. We conclude that frequent inhalation of PRC (up to 500 micrograms/day) via a jet nebulizer provides rapid relief from acute asthmatic attacks, and is safe clinically even in aged asthmatics receiving intravenous steroids. PMID- 1289632 TI - [A case of Legionella pneumonia with myelodysplastic syndrome]. AB - A 40-year-old man was admitted with high fever and cough. Pneumonic shadows of the left middle and lower lung fields increased rapidly, and his blood gases worsened. Initial treatment with cefmenoxime, piperacillin, and minocycline was ineffective. Administration of rifampicin was started for suspected legionella pneumonia, but it did not control the spread of the pneumonia shadows. After addition of an antifungal agent and trimethoprim-sulfamethoxazole, his symptoms gradually improved. Isolation of Legionella pneumophila from sputum specimens collected on the 4th day of admission confirmed the diagnosis on day 10. The patient was then given oral rifampicin plus cefmenoxime to prevent mixed infection, and showed a satisfactory improvement. Legionella pneumonia developed secondary to compromise of the patient's immunity due to steroid therapy for MDS. After recovering from Legionella pneumonia, the patient subsequently developed tuberculous pleurisy and Pneumocystis carinii pneumonia, which were cured by antituberculous therapy and trimethoprim-sulfamethoxazole. However, acute hepatitis followed by hepatic failure developed, and he died on day 121 after admission. PMID- 1289633 TI - [Theophylline toxicity in a patient with status asthmaticus]. AB - A 70-year-old woman was hospitalized for status asthmaticus. The level of CRP was high and chest roentgenogram showed infiltrative shadows in the left middle lung field. Artificial respiration and continuous infusion of methylprednisolone and aminophylline 750 mg/24 hr were performed. Eight hours after admission, seizures suddenly occurred. At this time, brain CT showed no abnormal findings. The seizures were thought to be induced by theophylline toxicity, since serum theophylline concentration was high at 69.9 micrograms/ml. Because theophylline clearance of the patient in a clinically stable condition was normal, it was speculated that theophylline clearance was reduced during status asthmaticus. It is thought that this rare case of theophylline toxicity occurred due to reduction of theophylline clearance during status asthmaticus associated with pneumonia. PMID- 1289634 TI - [A case of allergic bronchopulmonary aspergillosis with no history of bronchial asthma]. AB - A 53-year-old male was admitted to our hospital because of an abnormal shadow in the left upper lung. Bronchofiberscopy revealed edematous mucosa and pus at the orifice of the left upper lobe bronchus. Pathological examination revealed bronchial inflammatory change with infiltration of eosinophils and also the existence of aspergillus in the pus. Mild eosinophilia and elevation of serum IgE level were observed in the peripheral blood, and serum precipitin against Aspergillus fumigatus was positive. Bronchogram showed central bronchiectasis, and the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. In cases of ABPA, bronchial asthma is usually present prior to presentation, but this patient had no history of asthma even though airway hyperresponsiveness to methacholine was confirmed. PMID- 1289635 TI - [Three cases of chronic respiratory tract lesions associated with adult T-cell leukemia (ATL)]. AB - Three cases of chronic respiratory tract lesions as a complication of adult T cell leukemia (ATL) are reported. Case 1 was seropositive for HTLV-1 on recent examination following treatment of bronchiolitis. Chest radiograph revealed over inflation of the lungs and bilateral diffuse small nodular shadows. Pulmonary function test resulted hypoxemia and mixed ventilation disorder. Pathological examination confirmed lymphocytic infiltration of the bronchiolar wall. Both clinically and pathologically the patient was diagnosed as having diffuse panbronchiolitis (DPB). Therefore, this case was considered to be the bronchiolar type of HTLV-1 associated bronchiolo-alveolar disorder (HABA). The other two cases with smoldering or chronic ATL presented with long-standing symptoms of productive cough due to chronic respiratory lesions. We consider that all three cases had HTLV-1 virus associated pulmonary lesions, but with different clinical and pathological presentations. Among 12 cases of bronchiolitis experienced at our hospital, three were positive for HTLV-1. PMID- 1289636 TI - [A case of idiopathic pulmonary fibrosis with histology of usual interstitial pneumonia that responded to pulse therapy followed by combined immunosuppression with prednisolone and azathioprine]. AB - A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8 mg/kg) and azathioprine (15 mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia. Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %DLco 72%, PaO2 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects. PMID- 1289637 TI - [A case of cardiac sarcoidosis associated with various clinical symptoms and thrombocytopenia]. AB - A 29-year-old man presented with acute onset of high fever, chest pain and dyspnea. Chest X-ray film showed diffuse interstitial shadows, a cavitary lesion in the left upper lung field and cardiomegaly, but no lymphadenopathy. Abdominal CT scan showed hepatosplenomegaly and multiple small low density areas in the liver and spleen. Electrocardiogram demonstrated multifocal ventricular premature beats and ventricular tachycardia. Cardiac catheterization revealed left ventricular aneurysms. Sarcoidosis was confirmed by lung and liver biopsy. Drug therapy of prednisolone and mexiletine resulted in clinical improvement of symptoms, signs and chest X-ray film, but platelet count decreased gradually. It is suggested that an immune mechanism of sarcoidosis may have been the cause of this thrombocytopenia. PMID- 1289638 TI - [A case of primary alveolar hypoventilation syndrome with a good response to nocturnal low-flow oxygen inhalation and negative pressure ventilation]. AB - A 34-year-old female was admitted on June 25, 1990, for the evaluation of alveolar hypoventilation which worsened after her second delivery. She showed impairment of both hypercapnic and hypoxic ventilatory responses, and marked desaturation due to hypopnea and apnea during sleep. Although administration of methylxanthine and medroxyprogesterone was not very effective, after treatment with low flow oxygen, there was a marked decrease in the frequency and duration of desaturation during sleep and improvement of arterial daytime blood gases, which suggested the existence of hypoxic ventilatory depression in the pathophysiology of her nocturnal desaturation. Furthermore, the use of a negative pressure ventilator for 3 hours in the daytime for 10 days resulted in marked improvement of symptoms, arterial blood gases, respiratory muscle strength, and the frequency and duration of sleep desaturation. These findings suggest that both low flow oxygen therapy during sleep, and daytime negative pressure ventilation may be beneficial in patients with primary alveolar hypoventilation and central sleep apnea syndrome. PMID- 1289640 TI - [A case of eosinophilic pneumonia with diffuse reticular shadows and scattered nodular shadows on chest X-ray film--comparison of findings of chest X-ray and lung histology]. AB - A 47-year-old woman was admitted to our hospital because of dry cough and throat discomfort. Chest X-ray film showed reticular shadows with Kerley B line and scattered nodular shadows. Blood examination revealed normal WBC count (5100/mm3) with eosinophilia (21%), negative CRP, elevated ESR (49 mm/l hr), normal IgE level and positive antinuclear antibody with speckled pattern. Skin tests and precipitating antibodies for common allergens were negative. Results of arterial blood gas analysis and respiratory function test were almost normal. Bronchoalveolar lavage fluid yields 85.7% eosinophils, which suggested eosinophilic lung disease. To establish the diagnosis, thoracotomy was performed and lung specimens were obtained from S3a and S8a. In the area of the nodule, the alveolar spaces were filled with eosinophils and mononuclear cells, with no evidence of vasculitis, granuloma or parasites. Alveolar spaces were almost preserved in residual areas. The walls of air ways, pleura and lobular septa were heavily infiltrated with eosinophils and mononuclear cells. Thus, open lung biopsy confirmed the diagnosis of idiopathic eosinophilic pneumonia. The areas of intraalveolar filling with eosinophils and mononuclear cells were found to correspond to the nodular shadows on chest X-ray film. The relationship between the findings of chest X-ray films and lung histology are discussed. PMID- 1289639 TI - [A case of endobronchial minute leiomyoma and literature review of the 66 cases of endotracheal and endobronchial leiomyoma reported in Japan]. AB - A case of endobronchial minute leiomyoma successfully treated by bronchoscopically directed forceps biopsy is described. A 42-year-old male with a 20 pack-year smoking history was admitted for dry cough occurring at night. Chest X-ray showed no abnormal shadows. The tumor, measuring 2 by 2 mm, was located in the right B7. The clinical characteristics of the 66 cases of endotracheal and endobronchial leiomyoma reported in Japan are also discussed. The male to female ratio of this disease was 2:3. Middle-aged people were most, commonly affected. Usually, obstructive pneumonia or atelectasis, which develops distal to the lesion, causes respiratory symptoms and chest X-ray abnormality. However, 10% of cases were asymptomatic and 30% had a negative chest X-ray. There were 7 cases of endobronchial minute leiomyoma, measuring less than 10 mm in diameter. Of these, three cases had only hemoptysis and had no chest X-ray abnormality. In such cases fiberoptic bronchoscopy is may be the only useful procedure for the diagnosis of this disease. PMID- 1289641 TI - [Two cases of familial pulmonary arteriovenous fistula]. AB - Two cases of familial pulmonary arteriovenous fistula are reported. Case 1: A 54 year-old woman was admitted with exertional dyspnea. An abnormal shadow on chest X-ray had been noted since the age of 37 years. Pulmonary angiography demonstrated bilateral pulmonary arteriovenous fistulas. Case 2: A 25-year-old man, the son of Case 1, was admitted for operation for the same disease. The mother and son both suffered from repeated epistaxis due to Rendu-Osler-Weber disease. In order to reserve pulmonary function, fistulectomy was performed in both cases, and their subsequent clinical courses were good. PMID- 1289642 TI - [Child psychotherapy in medical practice and the clinic--15 years of the "Bruhl Model"]. AB - Living in an industrial society places considerable stress on children and on adolescents, to which they react with behavioural disturbances and psychosomatic disorders. So far, physicians have been trained only insufficiently at universities with regard to psychotherapy, which means they cannot cope sufficiently with such problems if they are confronted with them in their clinical and practical work. Hence, a continuing education programme called the "Bruhl Model" has been worked out which imparts knowledge on child psychology and child psychotherapy by means of three-year courses based on depth psychology. This corresponds to the "small-scale psychotherapy in medical practice" as conceived by J. H. Schultz and M. Balint. This educational programme has been largely adapted to the demands made at the Manheim Physicians' Congress in 1977 with regard to acquiring adequate proficiency in the subject of psychotherapy, and has been accepted by the German professional boards of physicians. 600 colleagues have since been undergoing this training during the past 15 years with success. The present seventh training course is now also open to the colleagues from the new German Laender of the former GDR. PMID- 1289643 TI - [Clinical importance of Helicobacter pylori infections in childhood]. AB - Within the last ten years an increasing number of Helicobacter pylori-related inflammatory gastroduodenal diseases in children has been reported. The aim of this paper is to describe the range of Helicobacter pylori infections in children including diagnosis and treatment by application of colloidal bismuth salts. PMID- 1289644 TI - [Vaccination--duty and voluntary consent]. AB - High mass inoculation rates--e.g. against measles, mumps and rubella or German measles--are mandatory in highly industrialised countries to keep circulation of wild strains of viruses as low as possible. In the GDR this was achieved, inter alia, by compulsory vaccination. Although compulsory vaccination is possible in the FRG as well, in accordance with the Federal Epidemics law, it needs a special ordinance requiring to be approved by the Federal Council. This, in turn, will be forthcoming only if there is an incidence of infectious diseases occurring in a malignant form of if it is to be expected that they will be spreading in the manner of an epidemic. Experiences gathered in other European countries (France, Italy) and in the U.S.A. have shown that success of compulsory vaccination depends on early control. Examples in individual Federal Laender and in England prove that high mass inoculation rates can be achieved even without compulsion if there is close cooperation between practising paediatricians and Public Health services. PMID- 1289645 TI - [School performance of former premature infants in the first four years of school]. AB - School achievement during the first four grades was analysed by means of subject marks in 203 prematurely born and in 140 maturely born children. In subjects referring to behaviour in the classroom, no statistically significant differences in average marks could be found between prematurely born children and the control group. The average marks in performance subjects were slightly higher in the subgroup of very prematurely born children. However, statistically significant lower marks were observed in the subject of sports only, and for formerly immature children also in the subject of manual training. The higher the educational level of the mothers, the better the average marks without sports. No relationships between school performance and manifestation of postnatal risk factor like Apgar score, blood gas values and duration of oxygen dependency could be seen. These results demonstrate that school performance of former premature infants lies within the normal variance of their grade. PMID- 1289646 TI - [Rate of intrauterine growth retardation at the Leipzig Perinatal Center comparing the years 1982 to 1984 with 1987 to 1989]. AB - Referring to the number of all live-born children, hypotrophic newborn (IUGR) were classified at the Centre for Perinatal Care in Leipzig into two periods of time. Based on the 5th Kyank-percentile 6.5% hypotrophic newborn were classified into period A (1982-1984) and 5.0% hypotrophic newborn were classified in period B (1987-1989). The proportion of hypotrophic newborn with a birth weight < 2500 g amounted to one quarter of all infants (except multiple birth) with low birth weight in period A and to one fifth (20.7%) in period B. The decrease in the rate of hypotrophy in these infants affected nearly exclusively the mature ones. The number of infants with extreme intra-uterine growth retardation amounted to 29% (99 in 329) in period A and to 24% (58 in 238) in period B. The rate of hypotrophy in stillbirths decreased from 44% to 33%. In this process the proportion of extremely hypotrophic stillbirths amounted to 47% in period A, whereas it decreased to only 26% in period B. PMID- 1289647 TI - [Pneumococcal cellulitis]. AB - Streptococcus pneumoniae as a cause of cellulitis is rarely reported in children and adults. We report on an infant with facial cellulitis due to pneumococci and review already described cases since 1975. The main features of this infection, underlying diseases and problems of diagnostics and therapy are discussed. PMID- 1289648 TI - [Mendelson syndrome in childhood]. AB - Mendelson's syndrome is characterized by bronchoconstriction, intraalveolary pulmonary oedema and insufficiency of the right heart. We report an unusual case of Mendelson's syndrome in infancy. The morphological findings, combined with the discussion of the pathophysiological stages, are presented. PMID- 1289649 TI - [Arteriovenous fistula of the blood vessels of the neck--a rare differential diagnosis of venous hum in childhood]. AB - In a case report it is shown that in rare circumstances there might be an extracardial organic cause for heart murmurs sounding accidentally. In a child with the finding of a venous hum an arterio-venous fistula between the right common carotid artery and the right internal jugular vein could be demonstrated by colour-coded echocardiography. The clinical relevance of this finding is discussed. PMID- 1289650 TI - [Acute gastroenteritis and acute obstructive bronchitis after mumps-measles rubella (MMR) preventive vaccination? The Pediatric Vaccination Counseling Service]. PMID- 1289651 TI - [Tetanus-diphtheria preventive vaccination: how to proceed when the young child is already "overimmunized"? The Pediatric Vaccination Counseling Service]. PMID- 1289652 TI - [Physician graduate and continuing education from the viewpoint of new legal requirements]. AB - Continuing and specialist education are inseparably linked to professional activities. The changes and especially the new legal aspects that have arisen since the GDR joined the FRG, are described. PMID- 1289653 TI - [Legal framework for vaccination]. PMID- 1289654 TI - Project lifestyle: developing positive health lifestyles for schoolchildren in Antigua. AB - Countries of the English-speaking Caribbean are in epidemiological transition. Following 30 years of socioeconomic change, obesity and chronic diseases have almost replaced malnutrition and infectious diseases as major health problems. Major risk factors for this modern epidemic are lifestyle-related. Project Lifestyle seeks to develop positive health lifestyles in schoolchildren gradually, sequentially, and systematically from grades 1-12 and throughout the school system on the island of Antigua. The four health habits addressed include weighing right, eating right, doing daily physical exercise, and having a positive self-concept. Since risk interventions with schoolchildren have produced positive results in several developed countries, this project developed an intervention methodology in the Caribbean context. PMID- 1289655 TI - Patterns of alcohol and other drug use in an Iowa community. AB - From a baseline survey of high school students in two school systems, information was obtained to describe patterns of alcohol and other drug (AOD) use and adverse consequences of use, compare indices of AOD use and consequences for grade level and gender differences, and examine relationships of indices to selected individual, family-related, and social competence/adjustment-related risk factors. Though use of illicit drugs was reported at low levels, prevalence of drinking and incidence of binge drinking were relatively high. Increases in AOD use and adverse consequences with age and grade level were found, but gender differences were not found. Relationships of AOD use and adverse consequences to selected individual, family, and social risk factors were consistent with a substantial body of prior work but exceptions were found. Strongest correlations to both indices were found for risk taking, sense of mastery, family management/cohesion, peer pressure, and social/school adjustment. PMID- 1289656 TI - Sources of stress in children with asthma. AB - Children experience stressors related to self-concept and school, family, and peer relationships. This study of children with asthma determined their perceptions of the frequency and severity of stressors they experience other than their asthma. Children with asthma are similar to peers with regard to perceptions of stressors. Teachers, health professionals, and parents should consider children with asthma as normal children who have an additional source of stress--a chronic illness. Results suggest perceptions of most stressors relate more strongly to gender-role development than to asthma. Children with asthma rated feeling left out of the group and not being good enough at sports as serious stressors. School personnel could be instrumental in encouraging management and prevention of exercise-induced asthma and promote all children's full participation in physical activities. Further examination of the relationship between stress and asthma is needed. PMID- 1289657 TI - Using the PRECEDE model to determine junior high school students' knowledge, attitudes, and beliefs about AIDS. AB - The effectiveness of a one-period school-based AIDS education program on an adolescent population of seventh and eighth grade students (N = 585) was determined. An instrument based on the PRECEDE model was used to assess program effectiveness. Three-way analysis of variance indicated significant differences (p v .01) between pretest to posttest scores for knowledge, attitude, and beliefs for those who received the program versus those who did not by grade and gender of students. The intervention group scored significantly higher than the comparison group on knowledge gain for both seventh and eighth grade students and for males and females. On attitude items, a significant increase occurred from pretest to posttest for eighth grade students who received the program, but not for seventh grade students. The experimental group of eighth grade students scored higher on the attitudes component than the comparison of eighth grade students on the posttest. When attitudes were examined by gender for females in the educational intervention, an increase occurred in attitude scores from pretest to posttest. While belief scores increased significantly from pretest to posttest for the experimental seventh and eighth grade students, significant increases occurred only for experimental group females. Findings support the contention that a one-class period AIDS education program can affect more than just knowledge since attitudes and beliefs also were partially affected. PMID- 1289659 TI - Comprehensive school health programs: the challenge for school nurses. PMID- 1289658 TI - Drug use and anticipated parental reaction among rural school pupils in Zimbabwe. AB - Study participants included 285 secondary school pupils in Zimbabwe who responded to a questionnaire assessing alcohol, tobacco, and marijuana use, and anticipated parental reaction to the pupil's drug-taking behavior. Results showed nearly 17% of the sample had used alcohol, 8% used tobacco, and 5% had used marijuana during the past seven days prior to questionnaire administration. Results regarding intentions to use alcohol, tobacco, and marijuana in the future show pupils' interest highest in using alcohol. Nearly 34% indicated intentions to use alcohol during the next year, while 16% reported intentions to use tobacco, and 12.9% indicated intentions to use marijuana. Nearly 17% reported they felt their parents would be favorable to their use of alcohol. Anticipated parental approval for tobacco and marijuana was 13.6% and 10.8%, respectively. Though current use and future intentions among the sample are not as high compared to similar populations in developed countries, this study suggests Zimbabwe should consider expanding its drug education effort in the school setting. Research to identify effective educational strategies to curb further increases in adolescent drug taking behavior also needs to be explored and identified. PMID- 1289661 TI - HIV instruction and selected HIV-risk behaviors among high school students- United States, 1988-1991. PMID- 1289660 TI - Increasing medication compliance and peer support among psychiatrically diagnosed students. PMID- 1289662 TI - Chemoprevention of premalignant and early malignant lesions of the prostate. PMID- 1289663 TI - Introductory remarks: development of chemopreventive agents for prostate cancer. AB - The term "cancer chemoprevention" refers to the prevention of cancer by intervening with drugs prior to the malignant (i.e., invasive) stage of carcinogenesis. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch at the National Cancer Institute. The testing of drugs for cancer chemoprevention differs from testing of those for cancer treatment. Chemopreventive drug trials involve healthy target populations, and the endpoints of reduced cancer incidence or mortality, reduced/eliminated precancerous lesions, or increased latency must be achieved with little or no drug toxicity. The design of cancer chemoprevention trials for prostate presents several problems, such as the age of the study population and undependable methods for detecting microscopic foci by sequential sampling. A major motivation for organizing this workshop is the development of strategies for the design of chemopreventive intervention trials for prostate cancer. One of the most difficult problems of chemoprevention drug testing is the necessity of lengthy trials due to the long developmental period of many cancers. This is especially true for prostate cancer. A major solution to the problem is the use of intermediate biomarkers, defined as morphological or molecular intraepithelial changes that can constitute short-term endpoints in chemoprevention clinical trials. They are categorized as histological, genetic, proliferation-related, and differentiation-related. Modulation of intermediate biomarkers, instead of cancer incidence, as trial endpoints would allow chemoprevention trials to be of shorter duration, to use fewer subjects, and to be of lower cost. Review of the current status of prostatic intermediate biomarkers, and methods for identifying and validating them, are also major reasons for convening this workshop. PMID- 1289664 TI - Prostatic intraepithelial neoplasia (PIN): current concepts. AB - Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts, ductules and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered to be a precursor to invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterized by basal cell layer disruption, basement membrane disruption, progressive loss of secretory differentiation markers, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognizing PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. PMID- 1289665 TI - Hormonal balance and the risk of prostatic cancer. PMID- 1289666 TI - Neoadjuvant hormonal manipulation: a strategy for chemoprevention trials. AB - Androgen ablation using hormonal manipulation is used extensively in metastatic prostate cancer; however, its use in localized disease combined with surgical extirpation of the gland has not been thoroughly and systematically investigated. The rationale for neoadjuvant therapy stems from the demonstrated effectiveness of androgen ablative therapy in metastatic disease and the high rate of "positive" surgical margins, especially in patients with Stage B2 disease. In addition, the essentially anecdotal clinical report of Scott and Boyd [1], using endocrine therapy plus radical prostatectomy in patients with Stage C disease, gives 15 year survival results comparable to those obtained by Jewett [2] in Stage 1 patients treated by radical prostatectomy. Finally, experimental observations in the androgen-sensitive mammary tumor (Shionogi) lend support to the concept of neoadjuvant hormonal manipulation. A pilot study of neoadjuvant endocrine therapy in 55 patients treated at Memorial Sloan-Kettering Cancer Center with 3 months of diethylstilbestrol (DES) (3 mg/day) prior to radical prostatectomy indicates marked reductions in prostate-specific antigen (PSA), although persistent evidence of adverse local tumor features was common. Some patients, however, exhibited evidence of significant downstaging. Whether or not any alteration in disease progression will accrue from demonstrated local downstaging is, of course, uncertain. However, clinical and laboratory effects of such treatment may provide a means for correlation with subsequent tumor behavior, and may prove useful in treatment decisions. Additionally, a decrease in the number of foci of grade 3 prostatic intraepithelial neoplasia (PIN-3) was noted in a small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289667 TI - Chemoprevention in prostate cancer: the role of difluoromethylornithine (DFMO). AB - The polyamines are normal cell constituents considered to have an important role in the regulation of proliferation and differentiation. DFMO is an irreversible, enzyme-activated, suicide inhibitor of ornithine decarboxylase (ODC), the enzyme responsible for the first and rate-limiting step in mammalian polyamine synthesis. Preliminary data show that DFMO inhibits tumor cell growth in vitro and in vivo, and that it demonstrates chemopreventive activity in a variety of animal tumors. The prostate contains some of the highest concentrations of polyamines and of polyamine-synthetic enzymes (including ODC) in the mammalian organism. ODC activity in the prostate was shown to be more susceptible to DFMO inhibition than in other organs. We have found the ODC activity of the Dunning R3327 rat prostatic carcinomas to be as sensitive to inhibition by DFMO as the normal rat prostate. Furthermore, DFMO was inhibitory to the growth of the tumor both in vitro and in vivo. Given the slow growth rate and long latency period of human prostate cancer and the preliminary DFMO data, we suggest that clinical trials to evaluate the chemopreventive potential of DFMO in prostatic carcinoma deserve serious consideration. PMID- 1289668 TI - Possible enhancement of prostate carcinogenesis by some chemopreventive agents. PMID- 1289669 TI - When is intervention warranted? AB - A chemoprevention trial in prostate cancer would be a formidable but potentially rewarding study. The current status of knowledge of drug interactions with, biomarkers of, and even the natural history of prostate cancer is insufficient to study all levels of men at risk. Currently, the most promising group to study is group I--those men with a high probability of developing prostate cancer but who do not currently have evidence of the disease. This could be a placebo controlled, prospective and randomized study with the endpoint being clinically detected prostate cancer. In addition, much may be gained from short-term pilot studies of "chemo-active" agents on morphologic and other biomarkers of prostate cancer initiated immediately before surgical removal. It is hoped that such studies may provide rationale for future efforts directed at preventing progression of premalignant or early prostate cancer lesions. PMID- 1289670 TI - The natural history of adenocarcinoma of the prostate. AB - All analyses of the efficacy of therapy for prostate cancer must control for the natural history of the disease. Over the past years, several long-term series involving several hundred patients have helped to describe the results of untreated disease. In general, most patients will not die of their disease, although approximately half of the patients will develop disease progression within 10 years. Predictors of progression include tumor stage, grade, and ploidy status. PMID- 1289671 TI - New relationships between prostatic intraepithelial neoplasia and prostatic carcinoma. AB - Our group has been studying the progressive molecular changes in prostatic epithelium which precede the invasive phenotype. Initial studies revealed similar alterations in cytoskeletal proteins between high grade prostatic intraepithelial neoplasia (PIN) lesions and invasive carcinoma. Specifically we observed an increased expression of certain cytokeratins and decreased expression of vimentin. We also noted a change in glycosylation as detected by Ulex europaeus staining. Using the latter technique we were able to microdissect and isolate nuclei from areas of low and high grade PIN lesions as well as from invasive carcinoma for morphometric analysis. Similarities in nuclear size, chromatin heterogeneity, and nuclear DNA content between low and high grade PIN and invasive carcinoma in carcinomatous specimens were noted. In contrast, these parameters were significantly different in low grade PIN lesions obtained from benign prostatic transurethral resection (TURP) specimens. In addition, DNA histograms revealed similar proliferative indices between high grade PIN and invasive carcinoma, which differed significantly from low grade PIN. Parameters thought to be relative to the invasive phenotype were also examined, such as the members of the metalloproteinase family; although normal luminal cells fail to express detectable levels of these enzymes, invasive carcinoma and even low grade PIN lesions express both the 72 kDa and 92 kDa type IV collagenase. Taken together, these data indicate that the dysplastic cells of PIN lesions and carcinomas are similar in nuclear and genomic features as well as protease expression. Our current working hypothesis is that these cells are already armed with the necessary proteases to invade the basal lamina but in an inactive form. Tumor progression requires an additional event of protease activation. PMID- 1289672 TI - DNA ploidy: early malignant lesions. AB - The nuclear DNA content of prostate cancer specimens, both needle biopsies and aspiration biopsy specimens as well as transurethral resection (TUR) chips and radical prostatectomy specimens, can now be reliably measured by standardized methods of flow and static image cytometry. For prostate carcinomas of every clinical stage (A1-D2), DNA diploid tumors have a better prognosis than tumors of a similar stage and grade which are non-diploid. Of particular importance to this symposium is the fact that DNA diploid stage D1 and D2 tumors treated early by androgen deprivation generally have a remarkably good prognosis. In contrast, those patients with DNA non-diploid tumors progress early despite androgen deprivation. Such a result suggests that DNA ploidy can be used to identify prostate cancers which are potentially sensitive to hormonal manipulation. Additional investigations from several groups indicate that early stage prostate malignant lesions, for example stages A1, A2, B1, and B2, are generally DNA diploid (about 75%). Swedish data suggest a steady progression of prostate cancer from early diploid to tetraploid, to non-tetraploid aneuploid, to multiple stemline aneuploid tumors with time and advancing stage. Taken together, these data suggest that the earliest detectable prostate carcinomas should be overwhelmingly DNA diploid. A large majority of these patients with early tumors should be candidates for "chemoprevention" by pharmacologic methods which reduce the effective androgen stimulation of prostate tumor cells. PMID- 1289673 TI - Aneuploidy and nuclear features of prostatic intraepithelial neoplasia (PIN). AB - Quantitative analyses (QAs) of prostatic intraepithelial neoplasia (PIN) helped to objectively define some traditional features of the lesion because, first, changes in value are represented by numbers and not by subjective evaluation of morphologic clues. QAs have also helped to identify subtle abnormalities. For example, the degree of nucleolar margination is a new diagnostic feature which can be easily evaluated as the proportion of nucleoli touching the nuclear membrane. Thirdly, QAs have provided useful insights into understanding some morphologic changes. PIN, in fact, appears to be characterized by complex changes which involve the secretory cells as well as the basal layer and which affect the surrounding stroma. In the epithelial lining, two types of simultaneous changes take place, the first in the nucleus (expression of abnormal proliferative and/or renewal activity) and the second in the cytoplasm (expression of the disorder in cell differentiation), pointing out that only PIN samples of high grade can be considered as having acquired the characteristics of a neoplastic lesion. PMID- 1289675 TI - Current and proposed biologic markers in prostate cancer. PMID- 1289674 TI - Transforming growth factor beta 1 as a biomarker for prostate cancer. AB - Using the mouse prostate reconstitution (MPR) model system, under conditions where the ras and myc oncogenes are introduced via a recombinant retrovirus into both the mesenchymal and epithelial compartments of the urogenital sinus, poorly differentiated prostate cancer is produced with high frequency (> 90%) using inbred C57BL/6 mice. Northern blotting and immunohistochemical analysis showed that the transition from benign prostatic hyperplasia (BPH) to prostate cancer is invariably associated with the induction of elevated transforming growth factor beta 1 (TGF-beta 1) expression. Similar analysis of TGF-beta 1 in human BPH and prostate cancer is consistent with our MPR results and indicates that the accumulation of extracellular TGF-beta 1 is significantly more intense in prostate cancer compared to normal or benign prostate tissues. Interestingly, where benign pathologies are observed in the prostatic stroma in the presence of benign prostatic epithelium, extracellular TGF-beta 1 is seen predominantly in the stromal compartment. Experimental studies clearly demonstrate that mRNA levels of TGF-beta 1 and other growth related genes are regulated by androgens in prostate cancer cells. Overall, our results suggest that elevated TGF-beta 1 is involved in the development of prostate cancer. Direct determination of TGF-beta 1 levels and distribution as well as analysis of localized and systemic effects produced by TGF-beta 1 may serve as useful biomarkers for prostate cancer. PMID- 1289676 TI - Prostate cancer tumor location as predicted by digital rectal examination transferred to ultrasound and ultrasound-guided prostate needle biopsy. AB - The advent of transrectal ultrasound (TRUS) and the Biopty instrument (Bard Urologic) has revolutionized prostate biopsy (PNB). Theoretically the systematic multiple biopsy approach offers the advantage of less sampling error with respect to presence of carcinoma, grade of carcinoma and sites of tumor within the gland. These parameters may be important in selecting the therapeutic approach and, if radical prostatectomy is contemplated, in modifying the operation as indicated based on tumor location. In the present investigation, we received specimens obtained from 100 men with clinically localized prostatic carcinoma who had previously undergone ultrasound-guided systematic random biopsy (TRUSPNB) along with TRUS and digital rectal exam (DRE). Among the 372 sectors with carcinoma identified in the 100 radical prostatectomy specimens, significant underrepresentation by TRUSPNB was noted (39% false negative). When an abnormality on either DRE, TRUS or TRUSPNB was observed, the sensitivity was 65%. The specificity was 89% when all three tests were abnormal. It would appear that preoperative assessment of tumor location is inadequate with the current modalities available. There may, however, be subsets of patients which would benefit by tumor location utilizing DRE, TRUS and TRUSPNB. PMID- 1289677 TI - Cancer detected incidental to simple prostatectomy (stage A1). AB - The incidence of stage A (incidental) adenocarcinoma of the prostate in transurethral resection (TUR) specimens is approximately 16%. This paper discusses the criteria for differentiating stage A1 versus stage A2 tumor, based on tumor volume and grade. Both the short-term (4 year) and long-term (8-10 year) natural history of untreated stage A1 prostate cancer are examined. Options to follow patients expectantly are presented. These include digital rectal examination and transrectal ultrasound. Specific problems relating to analyzing transrectal ultrasounds in patients who have had a prior TUR are addressed. Also, the unique aspects of transrectal ultrasound for stage A1 disease as it relates to the location of the lesion are expanded upon. The third option in the management of stage A1 disease is to monitor serum prostate specific antigen (PSA) levels. Areas covered include the sensitivity and specificity of PSA in general, and, in specific, serum PSA levels following TUR for stage A1 disease as a predictor of residual tumor. New data on a small group of patients who underwent delayed radical prostatectomy following diagnosis of stage A1 disease, where PSA data was available, are presented. The rationale for following patients with stage A1 disease by monitoring their serum PSA levels is supported by data from a group of men with normally sized prostates, benign prostatic hyperplasia, or cancer where longitudinal serum PSA levels were available. Finally, the option of radical prostatectomy for stage A1 disease is put forth. Data include a study of a large group of radical prostatectomy specimens performed for stage A1 disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289678 TI - The Lobund-Wistar rat model of prostate cancer. AB - Two models of preventable metastasizing autochthonous prostate adenocarcinoma (PA) have been described in Lobund-Wistar (L-W) rats: spontaneous PAs that develop at a mean age of 26 months; and induced PAs that develop at a mean time of 10.5 months. Both are similar in many respects to the counterpart disease in man. PAs develop spontaneously, and by induction through a combination of N methyl-N-nitrosourea (MNU)/testosterone treatments. Our investigations with L-W rats show that PA is manifested spontaneously in 26% of aged L-W rats, and by induction in approximately 90% of younger rats. It is characterized by metastatic adenocarcinoma initiated in, and expanding from, the dorso-lateral and anterior lobes, and occasionally in the seminal vesicles. It is regulated by genetic, hormonal, and age-related mechanisms. Spontaneous PAs are prevented by life-long moderate (25%) diet restriction and, in rats at risk of developing induced PA, by early treatments with estradiol, with dihydrotestosterone, with a retinoid, and by castration. While the "premalignant" stages of induced tumorigenesis are susceptible to intervention, the overtly malignant stage resists therapeutic trials with the same agents and procedures. The transition from dependency to autonomy has not yet been defined. PMID- 1289679 TI - Animal models for the study of prostate carcinogenesis. AB - Human prostate carcinogenesis has been viewed as a multi-step process involving progression from low histologic grade, small, latent carcinoma to large, higher grade, metastasizing carcinoma. However, recent data suggest that a variety of pathogenetic pathways may exist. The precise etiology and pathogenesis of human prostate cancer remain largely undefined. It is difficult to investigate stages in the development of human prostate cancer, but some animal models provide opportunities in this regard. Short-term treatment of rats with chemical carcinogens produces a low incidence (5-15%) of prostate cancer, provided that prostatic cell proliferation is enhanced during carcinogen exposure. Chronic treatment with testosterone also produces a low prostate carcinoma incidence. A high carcinoma incidence can only be produced by chronic treatment with testosterone following administration of carcinogens such as N-methyl-N nitrosourea (MNU) and 3,2'-dimethyl-4-aminobiphenyl (DMAB). Testosterone markedly enhances prostate carcinogenesis even at doses that do not measurably increase circulating testosterone. Thus, testosterone is a strong tumor promoter for the rat prostate. All such MNU- or DMAB-initiated and/or testosterone-promoted tumors are adenocarcinomas; most originate from the dorsolateral and anterior, but not ventral, prostate lobes. These tumors share a number of important characteristics with human prostate cancer. A high frequency (70%) of activation of the K-ras gene by a G35 to A mutation occurs in these carcinomas. Another high incidence prostate carcinogenesis model, representing a different pathogenetic pathway, involves chronic administration of estradiol-17 beta to rats in combination with low-dose testosterone. The resulting carcinomas are low-grade and originate exclusively from periurethral ducts of the dorsolateral and anterior prostate. While it is unknown whether testosterone is a tumor promoter in this system, preliminary studies indicate the formation of a DNA adduct in the target tissue, which suggests that estradiol-17 beta acts as a tumor initiating agent in this system. The high incidence models mentioned earlier are adequate for the study of chemoprevention of prostatic carcinogenesis. Analysis of shifts in the relative incidence of metastasizing carcinoma, grossly apparent but not-metastasizing carcinoma, microscopic-size carcinoma, and carcinoma in situ or atypical hyperplasia may allow study of the modifying effects of potential chemopreventive agents on tumor progression in these animal models of prostatic carcinogenesis. PMID- 1289680 TI - Human prostate cancer model: roles of growth factors and extracellular matrices. AB - A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGF beta, IGF1, IGF2, PDGF, EGF, TGF alpha and KGF, stimulated anchorage independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289681 TI - Immunologic structure and function of the gastrointestinal tract. AB - Host defenses within the gastrointestinal tract exclude bacteria and other intraluminal substances, which if released into the systemic circulation, would be toxic to the body. This is accomplished via complex interactions between these external pathogens and local immune responses and nonimmunologic processes. In addition to the mechanical and chemical barriers of the nonimmunologic defense system within the gastrointestinal tract, there is an effective immunologic barrier composed of aggregated and nonaggregated lymphoid cells. Gut-associated lymphoid tissue protects the intestinal mucosa from invading pathogens by intricate pathways of antigen processing. Gut-associated lymphoid tissue also transfers protection to other secretory sites within the body through the common mucosal immune system. The integrity of both the immunologic and nonimmunologic barriers may be affected by any number of pathologic insults as well as by nutritional influences. This article reviews the structural and functional characteristics of this complex and critically important host defense system. Specific nutrient requirements of the immunologic processes are discussed. PMID- 1289682 TI - Combined parenteral and enteral nutrition in severe trauma. AB - Early enteral feeding is increasingly advocated for the nutrition support of severely stressed patients. The successful use of this modality in critical illness is often limited by the patient's condition, the availability of access for feeding, and the patient's tolerance of the enteral formula. Factors such as abdominal injury or constraints on fluid volume also complicate nutrition support in this setting. Attention to a secure and well-maintained small bowel access tube and appropriate formula selection allow safe tube feeding in these patients. This case report describes the clinical course of a patient with severe chest and abdominal trauma who received enteral nutrition despite a large, open abdominal wound. PMID- 1289683 TI - Enteral feeding in the critically injured patient. AB - Metabolic support is an integral component in the care of the critically injured patient. When hypermetabolism occurs, there are increases in energy demands along with changes in substrate utilization. This article reviews the prospective randomized clinical trials that were undertaken at Denver General Hospital over the past decade that address both the timing of nutritional support and the route of administration in this critically injured population. Also discussed is a review of a meta-analysis that attests to the feasibility of early postoperative enteral feeding with the possibility of decreased septic morbidity in high-risk surgical patients. With the clinical knowledge gained from these trials, an algorithm for nutritional intervention was developed that represents our current standard of practice. PMID- 1289684 TI - Nutritional management of infants with bronchopulmonary dysplasia. AB - The nutritional needs of the child with bronchopulmonary dysplasia (BPD) vary significantly from those of a healthy child. To address the many special aspects of the nutritional care of the child with BPD, a nutrition management protocol was established at the University of Iowa Hospitals and Clinics. This protocol discusses caloric requirements; selection of enteral feedings; electrolyte, vitamin, and mineral supplements; growth, oral feeding advancement, and monitoring of nutritional status. Although many of the guidelines are supported by research, some are based on clinical practice. Many questions remain to be answered about the optimal nutrition therapy for these infants. One goal of this protocol is to stimulate discussion and research that will lead to a better understanding of the nutritional requirements of the BPD population. PMID- 1289685 TI - Enteral feeding and infection in the immunocompromised patient. PMID- 1289686 TI - Glutamine content of whole proteins: implications for enteral formulas. PMID- 1289687 TI - Strategic plan for the American Society for Parenteral and Enteral Nutrition. 1992. PMID- 1289688 TI - A.S.P.E.N. testifies before congress. PMID- 1289689 TI - The importance of the mucosal immune system. PMID- 1289690 TI - Indirect calorimetry: the search for clinical relevance. PMID- 1289691 TI - Use of indirect calorimetry in clinical nutrition. AB - The tremendous variability in resting energy expenditure makes efforts to predict caloric requirements difficult. Indirect calorimetry has provided a valuable tool in assessing energy expenditure, evaluating the way in which the body uses nutrient fuel, and designing nutritional regimens that best fit the clinical condition of the patient. The many indirect calorimetric instruments available vary in their application to clinical nutrition. The best metabolic studies are achieved by controlling the testing environment, accounting for the many clinical factors that may affect measurements, and eliminating potential sources for error. Although indirect calorimetry would seem to reduce the likelihood of complications from overfeeding, its greatest effect may be in cost savings by avoiding unnecessary nutritional support and in providing a means for clinical research. PMID- 1289692 TI - Nutrition support team recommendations can reduce hospital costs. AB - Providing nutrition support may be costly to hospitals under the prospective payment system. A nutrition support team, however, can be effective in controlling costs. To demonstrate the importance of the nutrition support team and to quantify the potential cost savings that can be achieved, a retrospective review of the effect of our team on hospital costs was conducted for the 12-month period of October 1989 to September 1990. The team supervises but does not regulate the use of total parenteral nutrition (TPN). During this time period, 176 patients received TPN. In 14 patients, the use of TPN was inappropriate, representing $65,349 in excess costs. After the cost of providing enteral nutrition to these patients (estimated at $2,430) was deducted, a net loss of $62,919 occurred. Nutrition support team action saved an additional $45,186 in hospital charges when recommendations to discontinue TPN were eventually heeded. Nutrition support team approval before TPN is initiated would achieve cost savings. PMID- 1289693 TI - Nitrogen balance studies in clinical nutrition. AB - Nutrition support is recognized as an important cofactor in altering morbidity and mortality of hospitalized patients. Paramount in delivering proper nutrition support is the accurate determination of baseline metabolic and nutritional status, thus influencing necessary protein requirements. After nutritional intervention, routine laboratory monitoring is used to measure the efficacy and to reassess metabolic stress level. Accurate determination of nitrogen excretion (and nitrogen balance) remains the standard in prescribing and monitoring the protein and nutritional treatment regimen. This article examines nitrogen excretion determinations in the clinical setting, including proper collection techniques, laboratory measurements, and analyses and their effect upon nitrogen balance studies. PMID- 1289694 TI - Selection of nutrition support regimens. AB - The selection of a nutrition support regimen should be the product of a logical, stepwise process. After an appropriate candidate is selected, the integrity and function of the gastrointestinal tract must be assessed to determine if nutrients can be administered enterally or must be given by vein. The anticipated length of therapy will help determine the type of feeding access. Long-term nutrition support requires permanent access, such as a percutaneously or surgically placed feeding tube for enteral nutrition or a tunnelled catheter or implanted port for parenteral nutrition. Formula selection for enteral nutrition, providing adequate liver and renal function, depends largely on the patient's ability to assimilate intact nutrients. The primary decision in parenteral formula selection is whether to provide the macronutrients as a mixed fuel system. The ultimate goal of nutrition support is to make a smooth transition to oral feedings while maintaining adequate nutritional intake. PMID- 1289695 TI - Setting priorities in health care: your money or your life. PMID- 1289696 TI - Nutrition support and health care reform--the work to be done. PMID- 1289697 TI - Reflections on home infusion therapy. PMID- 1289698 TI - Current status of home infusion therapy. AB - The growth of home infusion therapy has been influenced by external forces that have changed the access to and use of health care. As home infusion therapy expands into other alternate care settings, clinicians, regardless of discipline, must be cognizant of how daily clinical practice is affected by regulations, changes in legislation, and consumerism. PMID- 1289699 TI - The substance abuser and home intravenous therapy: above all else, do no harm. AB - Home care therapy is being challenged by changes in patient populations and technologic advances. The selection of appropriate candidates for home intravenous therapy is a critical issue faced by health care professionals. This process is more complex when the patient has a history of intravenous drug abuse. The issues concern patient compliance, safety, ethics, and legal responsibilities. Safe care depends on the ability of the patient to demonstrate a predetermined level of competence with catheter use. The potential use of illicit drugs may influence the ability of the patient to be compliant. Ethical principles of the patient's autonomy and free choice are weighed against the health professional's sense of beneficence. Legal guidelines stress informed consent, standards of care, and adequate documentation. An exploration of each of these factors outlines the potential risks and benefits and provides a basis for making clinical judgments. PMID- 1289700 TI - A standardized system for assessment and delivery of nutrition support in a large teaching hospital. AB - The nutrition support service (NSS) is consulted to evaluate and provide nutrition support to 500 patients per year. To facilitate this process, three forms--a consultation request form and preprinted parenteral and enteral nutrition order forms are used. The NSS Consult Request form was developed to provide consistency in medical, dietetic, nursing, and pharmacy patient assessments. This form is organized so that it includes clinical information necessary for nutrition assessment. Specifically, the NSS completes a nutrition assessment that includes a diet history; indirect calorimetry, only when indicated; a laboratory (metabolic) assessment; a clinical impression used to put the above-mentioned information into a nutrition perspective; and recommendations for either enteral or parenteral therapy. The recommendation for implementing nutrition support as either total enteral nutrition or total parenteral nutrition is made by using the respective order forms for enteral or parenteral nutrition. These include orders for specific formulas and additives and orders for laboratory monitors, nursing care, and criteria for notification of the physician. These forms facilitate the accurate transcription, preparation, and delivery of NSS orders by pharmacy, dietetics, and nursing departments. This approach provides an excellent framework in which to teach dietitians, pharmacists, nurses, and physicians a method for the delivery of appropriate nutrition support and provides a database for the performance of quality assurance analysis and clinical research. PMID- 1289701 TI - Severe hypophosphatemia in postoperative patients. AB - Severe hypophosphatemia may develop in postoperative patients for several reasons including alcohol withdrawal, diabetic ketoacidosis, nutritional recovery (refeeding) syndrome, and severe respiratory alkalosis. Severe hypophosphatemia may result in central nervous system abnormalities, muscle weakness, and renal, hepatic, cardiac, and respiratory dysfunction. Hypophosphatemia may be prevented by close monitoring of phosphorus concentrations in serum, especially in patients predisposed to developing this problem. Proper techniques for the maintenance and repletion of phosphate for both enteral and parenteral use are described. PMID- 1289702 TI - Bedside postpyloric placement of weighted feeding tubes. AB - A pilot study to evaluate a technique for the bedside placement of small-bore, weighted feeding tubes past the pylorus in critically ill patients is described. The technique involves the use of a #8 or #10 French small-bore, tungsten weighted feeding tube, specific patient positioning, and defined insertion techniques, including gastric distention with air. The tubes were placed at the bedside in the intensive care unit by the nutrition support team nurse. Successful postpyloric placement was achieved in 85 (83%) of 103 patients. Approximate time for successful insertion was 30 minutes. A follow-up study to define factors influencing success or failure of this technique is planned. PMID- 1289703 TI - The use of dietary fats in enteral and parenteral nutrition. PMID- 1289704 TI - Nutrition support teams--alive, well, and still growing. Results of a 1991 A.S.P.E.N. survey. AB - This report summarizes data collected from 1680 hospitals that responded to the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Nutrition Support Team Survey. The survey was conducted primarily to determine the prevalence, composition, and funding of existing and planned Nutrition Support Teams. Results tend to verify the importance of the Nutrition Support Team within the hospital's organizational structure. In addition, A.S.P.E.N. hoped to develop a national directory of Nutrition Support Teams as a byproduct of the survey. Details about the Nutrition Support Team Directory appear at the conclusion of this report. PMID- 1289705 TI - Managing clinical learning. PMID- 1289706 TI - The answer to advanced midwifery courses. PMID- 1289707 TI - [The viability of a learning contract]. AB - A basic principle of teaching is that students should be actively involved in the educational process. A learning contract is not a substitute method for learning, but enables a student to have a certain amount of control over objectives, content, methods and evaluation of certain curriculum contents. The learning contract gives the student the opportunity to take responsibility for own learning and places the student in an active role with regard to learning. PMID- 1289708 TI - Detecting leprosy. PMID- 1289709 TI - Are the elderly coping with rising healthcare costs? PMID- 1289710 TI - Confidentiality--a minefield of difficulties. PMID- 1289711 TI - The development of professional nursing education 1860-1988. Part III: United States of America. PMID- 1289712 TI - Vegetarianism. PMID- 1289714 TI - Protecting the psychiatric patient's rights. PMID- 1289716 TI - [What does a psychiatric service demand of nurses?]. PMID- 1289715 TI - Wound care in a rural clinic. PMID- 1289718 TI - Zidovudine effective in all ethnic groups. PMID- 1289717 TI - Routine HIV testing before surgery. PMID- 1289719 TI - Clinical update: AIDS. PMID- 1289721 TI - Infection control in a hospital creche. PMID- 1289720 TI - Professional practice. Time to tell the truth? PMID- 1289722 TI - Ethics: sharing responsibilities between doctors and nurses. PMID- 1289723 TI - [Managing conflict!]. PMID- 1289724 TI - Wound care--interventions: haemostasis, cleansing, topical antibiotics, debridement, and closure. PMID- 1289725 TI - [Psychiatric nursing. The ideal and the practice]. AB - Psychiatric services at primary health care level are far from ideal. Under present conditions the PHCN is relatively uninvolved. This state of affairs will change when a new model proposed by the authors is implemented. This model involves primary prevention programmes; training of PHCNs in the classification and diagnostic criteria of psychiatric illnesses; developing skills in crisis management, therapeutic intervention and behaviour modification; knowledge of drugs and their side-effects; multi-professional team planning implemented by the PHCN; and 24-hour consultation services by specialists. PMID- 1289727 TI - "Why homoeopathy, wherefore reflexology?". PMID- 1289726 TI - Update on pharmacology: drugs and the gastrointestinal tract. PMID- 1289728 TI - Retinitis pigmentosa (RP). PMID- 1289729 TI - Drug rebound headache. PMID- 1289730 TI - [Migraine--considerations on the achievements in medicine]. AB - Migraine is among the most mysterious diseases. It has been known for centuries but as yet it has resisted the advances in medicine and has not revealed its aetiology, mechanism of headache and possibilities of treatment. Various theories on the pathogenesis of migraine and arguments for and against them are reviewed here. The most convincing hypothesis seems to be that which covers all the achievements in this field, that is the neuronal-vascular theory in which serotonin is given the role of the main biochemical factor. The diagnosis of migraine is easy if its history is known, but the first attack, especially if very severe, may be difficult to diagnose and should be differentiated from meningitis or intracranial haemorrhage. The modern imaging techniques confirm the development of transient ischaemia in the brain which can explain the aura and the post-attack manifestations. The treatment includes interruption of attack and prevention of further attacks. As long as the aetiology and pathogenesis of migraine remain not fully understood, the interruption of attacks seems to be the most adequate management and here new possibilities have been demonstrated connected with the discovery of serotonin receptors. Prophylactic treatment may be justified only in severe and frequent attacks and its effectiveness is temporary. In summary it may be stated that as yet only several unshakeable facts have been established in the aetiology and pathogenesis of migraine: heritability, serotonin, vascular system of the head, trigeminal nerve, cerebral centres of inexact location and factors provoking attacks. They all are forming a chain of relationships which remains in the realm of hypotheses. PMID- 1289732 TI - Cerebrospinal fluid flow. II. Physiology of respiration-related pulsations. AB - Cerebrospinal fluid (CSF) flow in the cerebral aqueduct and spinal canal was analysed using real-time magnetic resonance imaging measurement techniques. Respiration-induced rhythmic modulation of the cardiac-related oscillating CSF pulsation in the cerebral aqueduct and spinal canal was found. Deep inspiration was immediately followed by a marked increase in downward CSF flow in the cervical spinal canal, whereas a delay of about two heart beats was seen before downward flow from the third to the fourth ventricle increased. This pattern was also detected during yawning and was followed by a marked increase of blood flow in the internal jugular vein. PMID- 1289731 TI - Cerebrospinal fluid flow. I. Physiology of cardiac-related pulsation. AB - Cardiac-related motion of the cerebrospinal fluid (CSF) was investigated by analysis of the velocity-dependent phase of CSF protons and flow-dependent signal enhancement in magnitude images using ECG-gated FLASH sequences. In the cerebral aqueduct, CSF flow from the third to the fourth ventricle begins 200 ms after the R-wave of the ECG and simulates an arterial pulse wave pattern. It lasts about 60% of the cardiac cycle and is followed by backflow from the fourth to the third ventricle, which is slower and shorter. In the spinal canal, oscillating caudad motion precedes flow from the third to the fourth ventricle by about 50-100 ms and is superimposed on a bulk flow, which moves simultaneously in opposite directions in separate subarachnoid channels; it is directed mainly caudally in the anterior cervical subarachnoid space. PMID- 1289733 TI - Cerebrospinal fluid flow. III. Pathological cerebrospinal fluid pulsations. AB - Cardiac- and respiration-related movements of the cerebrospinal fluid (CSF) were investigated by MRI in 71 patients. In most patients with arteriosclerotic occlusive vascular disease CSF pulsations are normal. Decreased pulsatile flow is detectable in those with arteriovenous malformations, intracranial air and following lumbar puncture and withdrawal of CSF. Increased pulsatile flow in the cerebral aqueduct was found in 2 patients with large aneurysms, idiopathic communicating syringomyelia and in most cases of normal pressure hydrocephalus (NPH). CSF flow in the cervical spinal canal is, however, reduced or normal in NPH, indicating reduction of the unfolding ability of the surface of the brain and/or inhibition of rapid CSF movements in the subarachnoid space over its convexity. PMID- 1289734 TI - MRI of anterior spinal artery syndrome of the cervical spinal cord. AB - Cervical spinal cord lesions in the anterior spinal artery syndrome were delineated on magnetic resonance images (MRI) in four patients. The lesion was always seen anteriorly in the cervical cord. On T2-weighted images, the lesions appeared hyperintense relative to the normal spinal cord, while on T1-weighted images, two chronic lesions appeared hypointense, with local atrophy of the cord. In one case, repeated T1-weighted images showed no signal abnormality 4 days after the ictus, but the lesion became hypointense 18 days later, when contrast enhancement was also recognized after injection of Gd-DTPA; this sequence of intensity changes was similar to that of cerebral infarction. The extent of the lesion seen MRI correlated closely with neurological findings in all cases. Although the findings may not be specific, MRI is now the modality of choice for confirming the diagnosis in patients suspected of having an anterior spinal artery syndrome. PMID- 1289735 TI - MRI in chronic spinal cord trauma. AB - Eighty-seven patients aged 16-68 years have been examined by magnetic resonance imaging (MRI) following spinal injury. The MRI findings have been correlated with length of history between trauma and investigation, extent of residual function and site of injury. They include changes at the site of injury consistent with myelomalacia in 37%, a syrinx in 40%, persistent cord compression in 32% and atrophy in 18%. An extensive syrinx can develop within 2 months of injury and it is nearly twice as common in patients with complete paralysis as in those whose paralysis was incomplete. It is suggested that investigation and management of spinal trauma should include early and repeated MRI examinations to detect sequelae at an early stage. PMID- 1289736 TI - Nerve root and sciatic trunk enlargement in Dejerine-Sottas disease: MRI appearances. PMID- 1289737 TI - Magnetic resonance angiography of extracranial carotid and vertebral arteries, including their origins: comparison with digital subtraction angiography. AB - Although carotid bifurcation stenoses are not the only lesions of the extracranial cerebral arteries, magnetic resonance angiographic (MRA) studies to date have concentrated on the carotid bifurcation. We compared digital subtraction angiography of the extracranial portions of the cerebral arteries with MRA using an ordinary body coil, the time-of-flight method, and multiple transverse slabs which covered the arteries down to the aortic arch. Twenty-two patients (15 with arteriosclerotic diseases, 4 with aortitis, and 3 with tumours) had MRA using a 1.5 T magnet system with a three-dimensional fast imaging with steady state precession (FISP) technique. Thirty-nine carotid and 39 vertebral arteries were assessed by three radiologists with regard to stenoses or occlusions, graded as normal, mild (< 30%), moderate (30-60%) or severe (> 60%) stenosis, or occluded. Grading corresponded well in 81%; stenoses appeared more marked on MRA in 14% and were seen less clearly on MRA in 5%. When 26 carotid bifurcations were assessed separately, grading corresponded well in 95%. MRA is the only method which can display the whole course of the extracranial carotid and vertebral arteries non-invasively and satisfactorily. PMID- 1289739 TI - Magnetic resonance angiography of intracranial aneurysms: comparison with intra arterial digital subtraction angiography. AB - Magnetic resonance angiography (MRA) with flow rephased gradient-echo sequences is a new non-invasive method for vascular imaging. We compared MRA and intra arterial digital subtraction angiography in 18 patients with intracranial aneurysms to test whether MRA presently provides an alternative to cerebral angiography for the diagnosis of these anomalies. MRA showed 19 of the 22 aneurysms detected (86.4%). However, problems, especially with turbulent or slow flow, resulted in 6 studies (27.3%) with limited and 2 with questionable demonstration of an aneurysm, and 1 false negative study. At present, MRA is definitely inferior to angiography for the demonstration of intracranial aneurysms, due to its lower resolution and other limitations. PMID- 1289738 TI - Magnetic resonance angiography compared to intra-arterial digital subtraction angiography in patients with subarachnoid haemorrhage. AB - In order to evaluate the sensitivity and specificity of magnetic resonance angiography (MRA) in spontaneous subarachnoid haemorrhage, 14 patients with recent haemorrhage verified by CT or lumbar puncture were investigated with both selective intra-arterial digital subtraction angiography (IA-DSA) and MRA by two independent teams, each having the same preangiographic information. The results were compared with each other and whenever possible (all positive cases except one) with those of surgical intervention. Seven patients were identified by MRA and IA-DSA as having a single aneurysm on the circle of Willis, 1 an aneurysm of the posterior inferior cerebellar artery 1 an aneurysm of the internal carotid artery (siphon) and 2 patients with two aneurysms on the circle of Willis. MRA and IA-DSA both failed to demonstrate aneurysms in 2 cases. Three patients had negative results on both methods and no surgical intervention was attempted. The aneurysms ranged from 0.3 to 1.5 cm in size. In most cases there was agreement between MRA and DSA, leading us to believe that, if the proper protocols are followed, MRA is a powerful alternative to other established methods in the detection of intracranial aneurysms. At this stage it will not replace IA-DSA prior to surgery, but the ability to obtain various projections using 3D MRA may improve surgical planning. PMID- 1289740 TI - Bilateral aberrant cervical internal carotid arteries. PMID- 1289741 TI - Investigation of stroke in sickle cell disease by 1H nuclear magnetic resonance spectroscopy. AB - Localized proton nuclear magnetic resonance spectroscopy (MRS), obtained with stimulated echo and spin echo sequences, MR imaging (MRI) and MR angiography (MRA) were used to study the brain in 13 children and adolescents with sickle cell disease. Regions of interest (ROI) studied by MRS included regions appearing normal on MRI as well as regions showing complications of sickle cell disease, including focal deep white matter areas of high signal intensity (deep white matter ischemia, DWMI) seen on long TR images, focal atrophic brain areas, and infarcts. The findings in these studies are summarized as follows: Normal appearing regions on MRI have normal MRS. In ROI including small areas of DWMI, lactate elevation was not detected, but the levels of N-acetyl-aspartate (NAA) appeared slightly elevated. In areas of DWMI 1-2 cm in size, reduced blood flow could be seen on MRA and lactate elevation could be detected with MRS. When blood flow to a DWMI region was normal, NAA was reduced and there was little lactate elevation, as cell death had already occurred. ROI consisting of atrophic tissue had reduced NAA levels but total creatine levels were not changed. Sometimes lipids, presumably from broken cell membrane, could be detected. In regions of past massive stroke, all metabolites were absent except for small amounts of lactate or lipids. PMID- 1289742 TI - Discrepancy of xenon concentrations between end-tidal and blood collection methods in xenon-enhanced computed tomographic measurements of cerebral blood flow. AB - Using xenon-enhanced computed tomography for the study of cerebral blood flow, simultaneous measurements of end-tidal and arterial blood xenon concentrations using the blood collection method were performed to investigate the validity of substituting the end-tidal for the arterial blood xenon concentration. Simultaneous measurement by both methods was performed 68 times in 27 patients. There was no statistical correlation between the arterial blood accumulation rate constant obtained by arterial blood and end-tidal samples, nor between the arterial blood saturation value obtained by the two methods, even when correction was made for age. In brain tissue, all parameters calculated using the end-tidal concentration were lower than those using arterial blood. We therefore suggest that cerebral blood flow values calculated using end-tidal xenon concentration are useful only for qualitative cerebral blood flow mapping, and not applicable to absolute values of cerebral blood flow. PMID- 1289743 TI - Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies. AB - We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 men and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I positive and -negative patients. These findings, although consistent with demyelination, are not specific. PMID- 1289744 TI - Cerebellar T-cell lymphoma: an unusual primary intracranial neoplasm. AB - Primary T-cell lymphoma within the central nervous system is extremely rare. Imaging characteristics appear indistinguishable from the more common B-cell lymphoma. A case of such a primary tumor is discussed and the MRI and CT findings presented. PMID- 1289745 TI - [Study of mediastinal lymph nodes in lung cancer using transesophageal ultrasonography]. AB - Evaluation of mediastinal lymph nodes in patients with lung cancer is fundamental for their treatment and prognosis. Chest computed tomography (CT) is presently the most utilized diagnostic modality. In recent years endoscopic ultrasound (EUS) is being employed for this purpose. We retrospectively compared the results of CT and EUS staging of 35 selected patients with postsurgical stage. A total of 175 lymph node sites were examined. Results CT vs EUS were as follows: specificity 92% vs 98%, sensitivity 88% vs 84%, positive predicted accuracy 80% vs 96%, negative predicted accuracy 95% vs 94%, overall accuracy 92% vs 95%. The region most accessible by EUS evaluation were the paraesophageal lymph nodes; the most difficult were the right superior mediastinal nodes which cannot be imaged for anatomic reasons. EUS not only allows one to arrive at correct diagnosis with less false positive results, but also permits evaluation of lymph nodes which are not enlarged. We think that EUS, in combination with CT, is an appropriate modality for staging of mediastinal lymph nodes in patients with lung cancer. PMID- 1289746 TI - [Surgical emergency in thyroid disease: acute respiratory failure caused by tracheal obstruction]. AB - Diagnostic and therapeutic approach to emergency due to acute and severe respiratory compromise by thyroid goiters with tracheal obstruction is discussed. Such an alarming condition was observed in 5 (2.3%) out of 215 mediastinal goiters operated between 1967-91. Retrospective and critical analysis of these cases pointed out that preventive removal of a large goiter is the best prophylaxis; first management is not surgical, although urgent features. Admission to intensive care center and endotracheal intubation allow an adequate interpretation of the pathologic condition and operative troubles and risks. Diagnostic investigations, effective and kept to a minimum (chest x-ray, tracheo laryngoscopy, TAC), must be carried out without delaying thyroidectomy and prolonging intubation for days. The extraction of goiter is nearly always performable by the cervicotomic way. Whenever necessary endotracheal intubation obviates the need of tracheostomy for solving transient postoperative complications such as laryngeal oedema, local hematoma and recurrent nerves stupor. PMID- 1289747 TI - [Neoplastic adenopathies of the neck: role of tumors of the oral cavity and salivary glands]. AB - The Authors report a series of 386 non-selected cases of cervical adenopathies with systemic (23.1%) and secondary (76.9%) tumors, treated using both simple biopsy and radical surgery. The predominant sites were right (29.0%) and left (23.6%) laterocervical. Histological tests revealed that in relation to metastatic adenopathies the predominant histotype in the series as a whole was squamous carcinoma (29.5%). Within the scope of metastatic adenopathies, tumors of the oral cavity or salivary glands, if taken together, account for the highest percentage of incidence: 14.2%. Three points emerge from an analysis of the data: 1) in the presence of lymph node tumors of the cervical district, taken as a whole, approximately 21.8% may be attributed to tumors of the oral cavity and salivary glands; 2) in the context of metastatic adenopathies, the predominant histotype is squamous carcinoma, 38.4%; 3) the presence of a high percentage of metastatic adenopathies of the neck due to cancer of the oral cavity and adjacent salivary glands always requires the greatest care to commence integrated chemo radio-surgical treatment of prevent efficacy. PMID- 1289748 TI - [Cholecystectomy and duodenogastric reflux]. AB - With the aim of evaluating whether cholecystectomy causes an increase in duodenogastric reflux (DGR) 34 patient (12 males and 22 females, mean age 50 years) were examined before and 6 months after cholecystectomy. DGR was evaluated by assaying total and individual biliary acids in gastric juice and was expressed as fasting bile reflux (FBR) in mumol/h. The histology of gastric mucosa in endoscopic biopsies taken from the antrum and body was also analysed. FBR of total biliary acids rose from 2.4 mumol/h before surgery to 41.33 mumol/h after cholecystectomy (p = 0.000). A significant increase was observed for all the individual biliary acids. Histological tests of gastric mucosa revealed an increased percentage of chronic atrophic gastritis of the antrum following cholecystectomy. Histological conditions in the body were unaltered. The results of this study show that there is a significant increase in DGR (months after cholecystectomy together with increased histological damage to the mucosa of the antrum. Further studies are necessary in order to evaluate whether the two phenomena are related. PMID- 1289749 TI - [Cancer of the rectum and sigmoid. Our experience]. AB - The paper reports the Authors' experience during the period 1989-91 and refers to 80 operated cases of rectum-sigma cancer. Given that data reported in the literature affirm that the limit of oncological safety is 1.5-2 centimetres distal from the tumour, and owing to their use of mechanical staplers, the Authors were able to use the preferred anterior section followed by low or very low colo-rectal anastomosis in 96% of cases. Miles' technique for abdomino perineal amputation was only resorted to in 4% of cases. Tumours parameters, short- and medium-term complications and the results of a short-term follow-up are all discussed. The Authors compare their experience with that of other researchers reported in the literature. PMID- 1289750 TI - [Various types of small intestine occlusion. Case contribution]. AB - The Authors examine retrospectively all the cases of obstruction of the small bowel operated at the surgical department of the Verbania Hospital in the last twenty years. The records of 341 cases, 1.4% of the total amount of the surgical operations carried out in the same space of time, were retrospectively reviewed. The Authors consider the data relating to sex, age, interval between hospitalization and operation, surgical treatment, possible previous operations, post-operative stay in hospital and complications. Having found a rate of complications significantly higher in those cases of obstruction that have required the resection of one or more intestinal loops (in all 69 cases, among them 50 cases belong to the group of the adhesions and of the strangulation), the Authors conclude by underlining the importance of recognizing and treating in time the cases where there is an irreversible vascular suffering of the bowel. PMID- 1289751 TI - [Inguinal hernia repair with the Shouldice method. Our experience]. AB - From 1982 to 1990, in our Surgical General Department, we have replaced the traditional technique of inguinal hernia with Shouldice's method. This choice was treatment of the following considerations: few relapses happen compared to traditional operations. PMID- 1289752 TI - [Comparison of echo-Doppler and splenoportography in the hemodynamic evaluation of the portal system]. AB - The Authors discuss the instrumental diagnosis of portal hypertension, comparing echo-Doppler and splenoportography by celiac artery catheterization, performed on 42 patients with cirrhosis. From the data obtained, there may be observed a clear correlation between angiographic and echographic criteria, correlated to the degree of illness. In particular echo-Doppler whether it possible, in a non invasive way, to control the evolution of progressive haemodynamic resistance, and hepatic and splenic parenchyma, leaving to splenoportography the role to depict anatomic characteristics of portal circulation for a correct surgical program. PMID- 1289753 TI - [Experimental evaluation, in vitro and in vivo, of the risk of infection related to the use of the most common surgical sutures]. AB - Many parameters contribute to surgical infections. Of these, surgical sutures with their chemical and physical characteristics like tissue and cell reaction degree and bacterial adhesion, play an important role. Cell vitality, bacterial adhesion, cell reaction degree were tested "in vitro" and tissue reaction with an "in vivo" model on: plain catgut, silk, polyglycolic acid, polyglactin 910, polyglyconate, polypropylene and nylon. Vitality cell test did not reveal any cytotoxicity; bacterial adhesion showed a lower adhesion degree to synthetic materials; cell reaction showed an increase in soluble receptor (sIL 2R) values in all materials except catgut. Tissue reaction was higher for resorbable sutures, and lower for nylon. These results suggest that special attention should be paid to the choice of suture materials. PMID- 1289754 TI - [Intraoperative colon irrigation in emergency surgical treatment of lesions of the left colon and rectum]. AB - The Authors propose the use of intraoperative colon irrigation in emergency surgery of left-sided lesions of the colon. This technique allows the colon to be decompressed and cleaned at the same time with the possibility of performing a resection or hemicolectomy without having to resort to protective colostomy and its related problems of morbidity. PMID- 1289755 TI - [Mechanical staplers. Personal experience]. AB - The Authors briefly summarise their experience of using various types of mechanical staplers in abdominal and thoracic surgery with excellent results both in general and in terms of reducing operating times. PMID- 1289756 TI - [Zenker's diverticulum in the elderly. Description of a case and surgical treatment]. AB - The authors report a case of Zenker's giant hypopharyngeal diverticulum in an elderly patient who underwent surgery due to the severity of symptoms. This diverticulum, which is both juxtasphincteric and epiphrenal, has a pulsion pathogenesis: the presence of a hernia on the esophageal side (jato?), with which Zenker's diverticulum is frequently associated and which is often followed by reflux esophagitis, is enough to cause motor asynchronism of the crico-pharyngeal muscle which, in the presence of hypertonic conditions during deglutition, leads to the formation of a high-pressure pouch which is then responsible for the formation of the diverticulum itself. It is therefore important to check whether an associated esophageal pathology exists once Zenker's diverticulum has been diagnosed: X-ray examinations of the upper digestive tract are undoubtedly capable of identifying the presence of the diverticulum as well as other pathological associations. In the present case it was not possible to perform a sufficiently exhaustive X-ray examination in order to exclude associated esophageal pathologies. Endoscopy may be superfluous and contraindicated in cases of large diverticular pouches. Symptoms vary depending on the size of the diverticulum. A feeling of dysphagia may precede the appearance of the diverticulum, even by several years, before the onset of symptoms related to the ingestion of food: initially the patient may experience the sensation of a foreign body while eating due to the accumulation of ingested food in the diverticulum; this is followed by halitosis, sialorrhea, noisy deglutition, regurgitation of undigested food especially during sleep, and frequently bronchopulmonary symptoms "ab ingestis".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289757 TI - [Gastrointestinal hemorrhage from a duodenal diverticulum]. AB - Duodenal diverticuli are often asymptomatic and are occasionally found during the course of X-ray tests or autopsy. They are sometimes manifested in the form of symptoms related to a complication (hemorrhage, perforation, occlusion). The paper reports a case of gastrointestinal hemorrhage caused by a duodenal diverticulum which was then successfully operated. The Authors affirm that in these cases the resection of the portion of the duodenum with the diverticulum (provided the papilla is not affected) is preferable to direct hemostasis or duodenocephalopancreatectomy. PMID- 1289758 TI - [Solitary perforated diverticulum of the right colon. Five cases]. AB - Solitary perforated diverticulum of the right colon is a very uncommon acute disease in emergency surgery, and usually a preoperative diagnosis of acute appendicitis is performed. Five cases of solitary perforated diverticulum of the right colon are presented. Preoperative diagnostic difficulties as well as surgical procedures are discussed. PMID- 1289759 TI - [Thoracic neurinoma: a case of a giant neurinoma]. AB - Having observed 6 cases of benign tumours deriving from nerve sheaths, one of which was of exceptional size (19 x 11 x 10 cm), with an endothoracic localization over the past 5 years, the Authors analyse the etiopathogenetic problems, anatomo-clinical symptoms and the possible methods of treating these endothoracic tumours. Neurinomas represent between 60 and 70% of mediastinal neurogenic tumours which account for 20% of all cancers of the mediastinum. Their typical localization is the posterior mediastinum, along the paravertebral grooves, and the dimensions of these tumours vary between 3 and 8 cm, although on rare occasions they reach 15 cm. In all cases except that of the giant neurinoma, surgery took the form of straightforward enucleation. Follow-up has not revealed recidivation in any of the cases operated. PMID- 1289760 TI - [Isolated rupture of the right hemidiaphragm with complete herniation of the liver into the thorax. Considerations of diagnosis and therapy]. AB - The Authors report a case of right diaphragmatic hernia due to road-traffic accident. They discuss the problems of early diagnosis because it is delayed for multiple associated lesions or a low index of suspicion. The ratio of laceration of the left side to that of the right is twenty to one. The clinical and diagnostic data best able to lead to a rapid preoperative diagnosis are considered. The Authors recommended early operative treatment and the thoracic approach; thoracoabdominal incisions are more suitable whenever abdominal lesions are coexisting. The Authors stress the use of safety belts with three point fastener which have significantly decreases cranial and abdominal lesions, particularly if associated with two rolls up. PMID- 1289761 TI - [Adrenal cystic lymphangioma. A case report]. AB - Adrenal cysts are uncommon. A case of left adrenal cystic lymphangioma in 16 year old boy is reported. The adrenal cyst was a chance finding during radiological investigation for abdominal pain. Ultrasound and CT scan showed the cyst and suggested the correct diagnosis of cystic lymphangioma of the left adrenal gland. The patient underwent surgery and a left adrenalectomy was performed. Histology confirmed the previous diagnosis of cystic lymphangioma. PMID- 1289762 TI - [Intrathoracic meningocele. A case report and review of the literature]. AB - In this article the Authors describe a case of intrathoracic meningocele. That was diagnosed in a young asymptomatic woman after surgical resection. After a complete and accurate review of the literature, the Authors underline the rarity of the find while they also note the association of this pathology with Von Recklinghausen's neurofibromatosis. They also discuss etiology and clinical diagnostic aspects as well. In conclusion the Authors insist that with new diagnostic imaging techniques available today it is possible to accurately diagnose this disease preoperatively in most patients. This fact along with improved therapeutic regimens makes surgical excision almost free from the complications that were at one time observed. PMID- 1289763 TI - Sialic acid and epithelial differentiation in colorectal polyps and cancer--a morphological, mucin and lectin histochemical study. AB - Loss of O-acetyl substituents from sialic acid expressed in mucin secreted by hyperplastic polyps (21), adenomas (9), a mixed polyp (1) and adenocarcinomas (41) of the colorectum was investigated by mucin histochemistry (diastase PAS and mild PAS) and by lectin histochemistry (Arachis hypogaea or peanut agglutinin) with (nPNA) and without (PNA) prior neuraminidase digestion. Mild PAS and nPNA reactivity were closely correlated, indicating that loss of O-acetyl substituents at C7, C8 and C9 (hence mild PAS positive) and at C4 (hence neuraminidase labile) occur pari passu. These sialic acid alterations were characteristic of mucin secreted by both adenocarcinoma and hyperplastic polyp. The same changes occurred patchily or focally in adenoma. Five "serrated" adenocarcinomas resembled the hyperplastic polyp both morphologically and histochemically. Luminal secretions within cancers were classified as mucin-like (type I) and non-mucin-like (type II). Mild PAS was the most specific technique for mucin-like intraluminal material. However, accumulated luminal secretions (type I or II) and intracytoplasmic lumina were quite specific features of colorectal cancer and could be effectively highlighted by means of dPAS. PNA reactivity without prior neuraminidase digestion showed a distribution unlike nPNA. Whilst PNA expression was more cancer specific than either mPAS or nPNA, it was observed mainly in cancers secreting little or no mucus, thus limiting its value as a tumor marker. PMID- 1289764 TI - Histological behaviour of chronic hepatitis in patients treated with alpha interferon. AB - To evaluate the histological effects of alpha Interferon (IFN) therapy, serial liver biopsy specimens from 30 patients with chronic hepatitis were studied. The biopsies were examined using a scoring system. After 12 mths of IFN therapy responders were 8 out of 11 HBV infected patients, 10 out of 12 HCV infected patients and only 1 out of 7 patients with cryptogenetic hepatitis. As spontaneous improvement of hepatic changes is infrequent, our data indicate that in terms of histological patterns interferon therapy is effective in chronic viral hepatitis. PMID- 1289765 TI - Survey of congenital tumors in perinatal necropsies. AB - In an audit of 17,417 necropsies from 1939 to 1989 at the Royal Women's Hospital, Melbourne, Victoria, 46 congenital tumors comprising 24 teratomas, 8 vascular tumors, 6 neuroblastomas, three rhabdomyomas, two mesoblastic nephromas, one thyroid adenoma, one hepatic adenoma and one cerebellar medulloblastoma were found. The teratomas were generally large tumors and, because of their size and location, incompatible with extrauterine life. Ten teratomas were associated with polyhydramnios, three with obstructed labour, five of the fetuses were hydropic and four had malformations at sites distant to the tumor. Twenty teratomas occurred in stillbirths, half of whom were macerated. The vascular tumors were associated with polyhydramnios in three cases and hydrops fetalis in two. The neuroblastomas were all incidental findings. Four were intra-adrenal, one was an adrenal tumor which had metastasized to the liver and the remaining case was a small paravertebral lesion. Two of the three rhabdomyomas were multiple and one of these occurred in a case of tuberous sclerosis. One of the mesoblastic nephromas occurred in a hydropic fetus who had the Arnold-Chiari malformation. The thyroid and hepatic adenomas were small incidental lesions. The cerebellar medulloblastoma had led to marked hydrocephalus. Congenital tumors have different incidence, presentation and behaviour than those in childhood or adult life. The association of congenital tumors with congenital malformations and hydrops fetalis should always be remembered. PMID- 1289766 TI - Gross handling of impalpable breast lesion specimens. AB - The growing use of mammography has resulted in increasing numbers of impalpable breast lesion specimens requiring histopathological assessment. The examination of such specimens may be very time-consuming as multiple levels of many tissue blocks may need to be studied. Two grid localization methods are compared with a serial slicing method in an attempt to determine an efficient manner of identifying the impalpable lesion, and thus minimizing unnecessary processing. The serial slicing technique gives excellent radiological-pathological correlation, but is probably too complex for routine use. A simple cardboard and metal staple device gives very good localization, and is quick, easy, and cheap to use. PMID- 1289767 TI - The role of the surgical pathologist in the examination of the non-palpable breast lesion. AB - The specimen excised for the mammographically detected lesion is somewhat unique and requires special consideration by the surgical pathologist. The biopsy, in most instances, contains no grossly visible lesion and is relatively large so that blocking in its entirety is not practical. The pathologist needs to establish that the radiological abnormality is contained in the biopsy and to this end specimen radiography is required. Established prognostic parameters for breast carcinoma, such as tumor size, histological type, grade and hormone receptor status are equally applicable in the non-palpable breast lesion but consideration should also be given to the identification of epithelial proliferations which have increased risk for subsequent carcinoma. In addition, the recognition of ductal carcinoma in situ in the biopsy indicates potential for widespread disease, and lobular carcinoma in situ, a less commonly detected lesion in mammography, is associated with multifocality and disease in the contra lateral breast. Both lesions are also associated with increased risk of recurrence in the remaining breast tissue. Failure to observe the corresponding quantity of calcium seen in radiographs relates to the fact that calcium may occur, not only as calcium phosphate, but also as calcium oxalate, the latter not being stained by hematoxylin and eosin but readily detected by its birefringent nature in polarized light. Detailed correlation of serial thin slices of the specimen with radiographic features is largely an educational exercise but is the most time-consuming step in the examination of the non-palpable breast lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289768 TI - Application of low magnification image analysis cytometry to prostatic tissue. AB - Determination of the volume percentage of epithelial tissue present in prostatic tissue samples obtained by transurethral resection presents difficulties for high magnification (0.2-0.5 microns per pixel) measurement techniques due to the random orientation of tissue fragments when sectioned and the necessity of having to select "representative" areas for measurement. A low magnification (110 microns per pixel) image analysis technique was used to overcome these difficulties by allowing measurement of the epithelial tissue component to be made from the entire area of tissue available for microscopic examination. This technique which utilizes standard hematoxylin and eosin preparations was applied to 89 consecutive cases of benign prostatic hyperplasia, with measurement times of four mins per slide being obtained. Replicate measurement of 20 of these samples showed an average absolute difference between replicates of +/- 5.1 percent epithelial tissue. This method thus offers a simple, fast and practical alternative to high magnification methods of estimating the volume percentage of epithelial tissue when the selection of "representative" areas for measurement is complicated by specimen heterogeneity or when large numbers of specimens must be examined. PMID- 1289769 TI - Computer assisted quantitation of terminal hepatic vein connective tissue in the rat. AB - Computer assisted image analysis has been used to quantify the cellular and extracellular connective tissue component of rat liver terminal hepatic venules, in control animals and those exposed to 40% ethanol in drinking water. A significant relationship existed between the size of the terminal hepatic venule and the amount of connective tissue it contained in 14 of 15 controls and 17 of 18 ethanol exposed rats. Thickening of the terminal hepatic vein wall assessed to be present in ethanol treated rats by direct observation was confirmed by image analysis in all cases (p < 0.01). Significant differences between treated and control livers (p < 0.05) were detected by image analysis when not apparent to human observers. Sensitive quantitative assessment of terminal hepatic vein wall thickening was thus achieved by computerized analysis of liver sections. PMID- 1289770 TI - Platelet-derived growth factor and alternative splicing: a review. AB - The mitogenic and chemotactic potency of platelet-derived growth factor (PDGF) has linked this polypeptide to the pathogenesis of several disease states including atherosclerosis and neoplasia. We have reviewed the recent literature on aspects relating to the structure, distribution and biology of PDGF and its high-affinity cell-surface and intracellular receptors. In addition to platelets, several normal and tumor cells secrete the mitogen in one or more of three possible dimeric configurations. Alternative splicing of exon 6 in PDGF A-chain RNA results in the formation of two protein species with different carboxy termini. Initially, it was thought that the longer A-chain variant was processed only by transformed cells. However, recent evidence indicates that alternative splicing occurs in several cells which express the A-chain, including early Xenopus embryos. The functional significance of the exon 6 product, a highly basic region spanned by 18 amino acid residues (A194-211), is not precisely clear. We have summarized recent findings which implicate roles for A194-211 in the processing, secretion, and mitogenesis of the A-chain homodimer, nuclear transport signalling, and heparin binding. Thus, alternative splicing could play an important role in the modulation of the functional properties of the PDGF A chain variants per se and in the complex interactive network of polypeptide growth factors and cytokines. PMID- 1289771 TI - A method for enriching myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from human cord blood by accessory cell depletion. AB - Human cord blood provides a convenient alternative to bone marrow as a rich source of hemopoietic progenitor cells. This study reports a simple means for enriching a cord blood progenitor cell population by accessory cell depletion. Two methods of monocyte depletion were tested. A Cytodex 3 microcarrier system using collagen coated dextran beads was compared to the more commonly used method of plastic plate adhesion. The method of plastic plate adhesion gave a significantly higher cell recovery. T cell depletion using a recently characterized rat monoclonal antibody which fixes human complement was also investigated. A combined method of monocyte depletion by plate adhesion and T cell depletion resulted in the removal of > 96% of monocytes and > 98% of T cells. This led to a significant enrichment of myeloid (CFU-GM) and erythroid (BFU-E) colony growth. Such enriched progenitor cell populations provide a useful starting population for any study on hemopoiesis. PMID- 1289772 TI - Effects of cholera toxin on human colon carcinoma cell lines. AB - This study reports on changes in morphology and membrane transport in 5 human colon carcinoma cell lines treated with cholera toxin (CT). Three of the cell lines that grew as monolayers (LIM 1215, LIM 1899, LIM 2099) and 1 that grew as floating clumps (LIM 2408) did not show morphological changes after CT treatment. However, cell line LIM 1863 that grows as floating "crypt-like" organoids showed rapid and distinctive changes in morphology and membrane transport after CT treatment. At 1 and 6 hrs after CT treatment, light and transmission electron microscopy revealed rapid dilatation of the central lumen of organoids and the appearance of 2 populations of apical vesicular inclusions. The first population was unusual in being non-membrane bound and limited by fuzzy filamentous material. The second population was membrane bound. Scanning electron microscopy at 1-6 hr after CT treatment showed swelling and loss of surface microvilli on some, but not all, cells. At 24 hr after CT treatment the majority of organoids showed evidence of fluid accumulation and small apical vesicles coalesced to form large single vacuoles that obliterated normal cell morphology. By 48 hr, continued swelling produced extreme attenuation of the plasma membrane with cells taking on an "endothelial cell-like" appearance. The response to CT was dose dependent. Uptake studies using 86Rubidium and blocking studies using ouabain and amiloride indicated that CT is acting on the Na+/K+ ATPase membrane pump to cause the increased fluid uptake by LIM 1863 cells. This study is the first to report specific morphological changes in intestine-derived cells in response to CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1289773 TI - The putative melanoma tumor-suppressor gene on human chromosome 6q. AB - The tumorigenicity of malignant melanoma cells may be suppressed experimentally by the introduction into these cells of human chromosome 6 or mouse chromosome 4. These chromosomes share a homologous region, contained in human chromosome 6q12 21. Abnormalities of this human chromosomal region have been found frequently not only in cutaneous and uveal malignant melanomas, but also in a range of other tumors. In all these, mutations of tumor-suppressor genes on human chromosome 6q may be involved. Identification of this putative tumor-suppressor gene may give new insights into the biology of malignant melanomas, and could pave the way for new treatment for such tumors, based upon the tumor-suppressor protein which this gene is likely to encode. PMID- 1289774 TI - Myositis ossificans in childhood. AB - Myositis ossificans is a benign, localized, ossifying lesion of soft tissues that is rarely reported in young children. This paper describes two cases found in a search of the surgical biopsy files of the Adelaide Children's Hospital over the 30 yr period from 1962 to 1991, in boys both aged 7 yrs. Diagnosis was assisted by combined clinical, radiological and histopathological information (including an adequate well-orientated biopsy in Case 1 that demonstrated the characteristic growth pattern) enabling differentiation from other possibilities such as fibrodysplasia ossificans progressiva. PMID- 1289775 TI - Nursing datasource 1992. Volume III. Leaders in the making: graduate education in nursing. PMID- 1289776 TI - DNA cleaving modes in minor groove of DNA helix by esperamicin and calicheamicin antitumor antibiotics. AB - This study examines and compares DNA cleavage modes by several esperamicin derivatives and calicheamicin. We found that the deoxyfucose-anthranilate moiety is a key factor to determine their DNA cutting modes. Probably, the bulky moiety hinders the abstraction of hydrogen atom from deoxyribose by the C-1 carbon radical of phenylene diradical. On the basis of the experimental results, detailed DNA cleaving modes in DNA minor groove by esperamicin and calicheamicin have been discussed. PMID- 1289778 TI - Partial methyl phosphotriester-modification of oligodeoxyribonucleotides. PMID- 1289777 TI - Molecular mechanisms for controlling spontaneous and induced mutagenesis. AB - Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. We also deal with suppression of alkylation-induced mutations by O6-methylguanine-DNA methyltransferase. PMID- 1289779 TI - Facile and stereoselective synthesis of 2'-5'-oligothioadenylate by UO2(2+) ion catalyst. AB - The synthesis and characterization of 2'-5'-oligothioadenylate by UO2(2+) ion catalyst are described. The polymerization of imidazole-activated thioadenylate or thioinosylate yielded oligomers containing mainly 2'-5'-internucleotidyl blond and Rp configuration at phosphorous atom. PMID- 1289780 TI - Facile reductive cleavage of purine nucleosides to acyclonucleosides using diisobutylaluminium hydride (DIBAL): a new synthetic method for the preparation of 9-ribitylpurine derivatives. AB - Reaction of purine nucleosides, such as 2',3'-isopropylideneinosine (1a) and 2',3'-isopropylideneadenosine (1c), with diisobutylaluminum hydride (DIBAL) in dry tetrahydrofurane resulted in the formation of the corresponding 9-(2',3' isopropylideneribity)purines (2) in good yields. Oxidation of the ribityl derivatives (2) with NalO4 and subsequent reduction with NaBH4 gave the corresponding 9-(2',3',4'-trihydroxybutyl)-purine derivatives (4) in high yields. Deprotection of compounds 2 and 4 in 80% acetic acid gave the corresponding 9 (2',3',4'-trihydroxybutyl)purines (5) and 9-ribitylpurines (6), respectively. PMID- 1289781 TI - Regioselective halogenation of some 2,3-anhydro pyrimidine nucleosides with dilithium tetrahalocuprates. AB - The reaction of 1-(2,3-anhydro-5-O-trityl-beta-D-lyxofuranosyl)-2-O-methyluracil (1a) and its thymine analogue (1b) with dilithium tetrahalocuprate (Li2CuX4) revealed excellent to perfect regioselectivity, yielding 2,2'-anhydro-3' halonucleosides (2a-d), while the same reactions with 2,3-anhydro uracil and thymine nucleosides (4a,b) gave arabinosyl (5a-d) and xylosyl halohydrins (6a-d) with the respective product ratio of 7:3 to 8:2. compounds 5 and 6 were isolated as the 2-O-(7) and 3- O-mesyl derivatives (8). PMID- 1289782 TI - Synthesis of 2'-deoxy and 2',3'-dideoxynucleoside derivatives from thioglycosides. AB - The synthesis of both 2'-deoxy and 2',3'-dideoxynucleoside derivatives by the reaction of thioglycosides with nucleoside bases was examined. The stereochemical outcome at the anomeric position was found to depend on the protecting groups and the C-3 configuration in the sugar moiety, the kind of activator, and the reaction temperature. Based on these findings, 2'-deoxy-D-xylo nucleoside and 2',3'-dideoxynucleoside derivatives have been synthesized in beta-selective manner. PMID- 1289783 TI - The synthesis of cyclopropano nucleosides. AB - A tricyclic, fused cyclopropano nucleoside 8 containing a ketal group was synthesized by the one-pot seven sequential reactions of a trimesylated allofuranosyl adenine derivative 6 with Mg(OMe)2. When KOH was used instead of Mg(OMe)2, an alpha, beta-unsaturated ketonucleoside 7 was obtained. PMID- 1289784 TI - Synthesis and interaction studies of watersoluble nucleic acid analogs containing serine as a spacer. AB - Watersoluble nucleic acid analogs containing L- or D-serine as a spacer were synthesized. Thymine was used as nucleic acid bases of these analogs. The base contents of these analogs were 93-94%. These analogs were found to form stable polymer complexes with Poly A or DNA by specific base-base interaction, which were observed from hypochromicity of UV spectra. In both cases, the maximum hypochromicity values of PEI-L-Ser-Thy were higher than that of PEI-D-Ser-Thy. PMID- 1289785 TI - Synthesis and properties of oligodeoxyribonucleotides containing a mutagenic base, N4-aminocytosine. AB - Oligodeoxyribonucleotides containing a mutagenic base analog, N4-aminocytosine, 5'-AATTGC(am)AATT-3' and 5'-AATTAC(am)AATT-3' (C(am); N4-aminocytosine) were prepared by chemical modification of 5'-AATTGCAATT-3' and 5'-AATTACAATT-3', respectively. The values of Tm were 29 degrees C for 5'-AATTGC(am)AATT-3' and 32 degrees C for 5'-AATTGCAATT-3'. In contrast, no melting was observed for 5' AATTAC(am)AATT-3' and 5'-AATTACAATT-3'. These data show that the stability of C(am)-purine paris is C(am)-G > C(am)-A and that C(am)-G is less stable than C-G. This property is consistent with the incorporation specificity of N4-amino-dCTP during DNA synthesis in vitro. PMID- 1289786 TI - Synthesis and property of alpha-oligodeoxynucleotide phosphorothioate. AB - Unnatural DNA analog, alpha-2'-deoxy-oligoadenylate phosphorothioate bearing 3' normal monophosphate moiety was conveniently synthesized through phosphoramidite solid support method. The starting material of the DNA analog, alpha-2' deoxyadenosine, was prepared in a stereospecific manner by the coupling reaction between activated nucleobase and 1-chloro-2-deoxyribose derivative. PMID- 1289787 TI - The influence of oligodeoxyribonucleotide phosphorothioate pyrimidine strands on triplex stability. AB - The analogues of the homopyrimidine oligonucleotide dT15 has been synthesized. The analogues, contains phosphorothioate bonds of a mixture of diastereoisomers or one of the two stereoisomer (either Rp or Sp). The analogues were mixed under conditions conductive to the formation of triple stranded assemblies. The mixtures were characterized by their thermal stabilities (Tm values) and CD spectra. PMID- 1289788 TI - Interaction of antisense DNA with nucleic acids/proteins. AB - In order to study interaction of various types of labeled antisense DNAs were prepared. Fluorescein and 2,2,6,6-tetramethypiperidine-N-oxyl were the label molecules, which were introduced to 5'-end of oligonucleotides and their analogs. Interactions of labeled antisense DNAs with nucleic acids or proteins such as HSA, HIG and TF, were studied by UV, fluorescence depolarization spectroscopy, and ESR spectroscopy. Hybrid formation of antisense DNAs with oligonucleotides in solution could be monitored by the increase in fluorescence anisotropy (r) and by intensity change in ESR spectra. When phosphorothioate type antisense molecules anchoring fluorescein (F-OPT) were mixed with proteins, r drastically increased, whereas ODN slightly increased. These results suggest that OPTs have much more affinity for proteins than ODNs. PMID- 1289789 TI - Syntheses and properties of fluorescent labeled oligonucleotides containing deoxyethenoadenosine at 5' end. AB - The fluorescent labeled oligodeoxyribonucleotides which contain deoxyethenoadenosione (d epsilon A) at their 5' end were prepared by treating CPG bound oligonucleotides with 5'-DMTr-deoxyethenoadenosine-3'-H-phosphonate. The hybrid formation of d epsilon A-oligonucleotide with its complementary DNA was studied by fluorescence spectroscopy. The fluorescence of d epsilon A in a single strand was largely quenched by stacking interaction with the base at 3' position. When d epsilon A-oligonucleotides hybridized with their complementary strands, relative fluorescence quantum yields (Qrel) against d epsilon A changed in specific manners. These results suggest that d epsilon A-oligonucleotides are applicable to study the local structure of DNA in solution. PMID- 1289790 TI - Kinetics and thermodynamics of double-helix formation of self-complementary deoxyribooctanucleotides d(TCTATAGA) and d(TAGATCTA). AB - Double-helix formation of self-complementary deoxyribooctanucleotides, d(TCTATAGA) and d(TAGATCTA), with identical nearest neighbor base pairs has been studied by means of UV melting and temperature-jump techniques. The self complementary duplexes of both octanucleotides with identical nearest neighbors had similar stabilities: The stabilization energies of the octanucleotides at 25 degrees C were 5.8 kcal mol-1 for d(TCTATAGA) and 6.7 kcal mol-1 for d(TAGATCTA). On the kinetic curve the melting reactions finished within 20 ms for d(TCTATAGA) and 40 ms for d(TAGATCTA) at 20 degrees C. For both octanucleotides the rate constants of dissociation increased and the rate constants of association decreased with increasing temperature. PMID- 1289791 TI - Novel strategies towards construction of non-ionic and achiral backbones in antisense oligonucleotides. AB - A convenient synthesis of a thymidine (T) nucleoside dimer (T-3'-CH2-O-NCH3-CH2 4'-T) 12 has been accomplished via a nucleoside coupling reaction. An alternative synthesis of 3'-deoxy-3'-C-hydroxymethyl-thymidine is described. The new dimer and methodology is useful for the development of backbone-modified antisense oligonucleosides. PMID- 1289792 TI - Fluorescent-labeled oligonucleotides that exhibit a measurable signal in the presence of complementary DNA. AB - Oligonucleotide derivatives with a fluorescent dye were designed for exhibiting a measurable signal only when they bind to complementary DNA in aqueous solution. The oligonucleotide with a dansyl group at the specific 2'-sugar residue was synthesized by using the protected 2'-dansylaminouridine phosphorobisamidite. The dansyl-oligonucleotide conjugate binds to its complementary DNA to form duplex with a normal stability and exhibits enhanced fluorescence together with a blue shift in emission maxima after the hybridization. Another possible candidate involved the use of pyrene-excimer emission upon forming ternary complex between two pyrene-labeled oligonucleotide probes with target DNA. A new and general method for introduction of a pyrene fluorophore into the 3'- or 5'-terminal hydroxyl group of oligonucleotides via different linkers was developed. PMID- 1289793 TI - Separation and characterization of diastereoisomeric oligonucleotide. AB - For developing the antisense method, two types of oligonucleotides suitable for antisense molecules were explored for their essential properties. One is oligonucleoside phosphorothioate, and all their possible R/S diastereoisomers were separated and purified by reversed phase liquid chromatography. Isolated diastereoisomers have been investigated for the correlation between their configuration and hybridization manner. Separation, R/S characterization and spectroscopical properties of these oligonucleotides will be discussed. PMID- 1289794 TI - Double-helix formation of self-complementary chimeric oligonucleotides r(CG)nd(CG)3-n (n = 0, 1, 2, 3). AB - Double-helix formations of self-complementary chimeric hexanucleotides, r(CGCGCG), r(CGCG)d(CG), r(CG)d(CGCG), and d(CGCGCG), have been studied spectrophotometrically an thermodynamically in 1 mol dm-3 NaCl buffer. CD (circular dichroism) spectra showed that r(CGCGCG), r(CGCG)d(CG), and r(CG)d(CGCG) formed A-type double helix, while d(CGCGCG) formed B-type double helix. The stabilization energies of these helices at 37 degrees C obtained from UV melting analyses were 9.2 kcal mol-1 for r(CGCGCG), 8.2 kcal mol-1 for r(CGCG)d(CG), 6.8 kcal mol-1 for r(CG)d(CGCG), and 8.5 kcal mol-1 for d(CGCGCG), respectively. PMID- 1289795 TI - Purification and characterization of tRNA(adenosine-1-)-methyltransferase from Thermus thermophilus HB27. AB - A58, the conserved adenosine residue in the T psi C loop of tRNAs, is methylated to m1A 58 in an extreme thermophile, Thermus thermophilus HB27. The enzyme catalyzing this methyltransfer reaction was purified from the thermophle. The substrate specificity of the enzyme was investigated by using tRNA fragments. The enzyme can transfer the methyl group to the 3'-half fragment of E. coli initiator tRNA, indicating that the main recognition site of the enzyme exists in the 3' half of tRNA including the T-loop and the T-stem. PMID- 1289796 TI - Cloning and sequence analysis of the evgAS genes involved in signal transduction of Escherichia coli K-12. AB - We have cloned and sequenced new Escherichia coli genes which belong to member of the family of environmentally responsive two-component system and named evgA and evgS because their amino acid sequences were found the most homologus to the Bordetella pertussis bvgA and bvgS. They were mapped at 51 min. and extending from 6B9 to 7G9 in the Kohara miniset library of the E. coli chromosome. In fact, both EvgA and EvgS proteins predicted from their DNA sequences were identified in the in vitro coupled transcription translation system. When the evgA and evgS were expressed on multiple copy plasmid in an envZ deletion strain, ompC expression was also regulated by temperature, MgSO4 and nicotinic acid, by which virulence of Bordetella pertussis is controlled via BvgA and BvgS. These results indicate that ompC expression was controlled by in vivo cross-talk via EvgA and EvgS which can work in E. coli the same way as BvgA and BvgS. PMID- 1289797 TI - Activities of HIV-RNA targeted ribozymes transcribed from a 'shot-gun' type ribozyme-trimming plasmid. AB - We have constructed a "shot-gun" type ribozyme-trimming system. By concatenating several units, each consisting of a trans-acting ribozyme (targeted to HIV-RNA) and cis-acting ribozymes (trimming 5'- and 3'-ends of the trans-acting ribozyme), several kinds of trans-acting ribozymes can be liberated upon transcription and self-cleavage. Since each liberated HIV-RNA-targeted ribozymes can work independently, they can simultaneously cleave HIV-RNA at several different sites. Ribozymes were targeted at relatively conserved GUC-containing sites at LTR, gag and tat regions. PMID- 1289798 TI - DNA conformation of the region preceding the beta-lactamase promoter of pUC19 which is required for efficient transcription. AB - The upstream region of the beta-lactamase promoter of Escherichia coli plasmid pUC19 has a DNA curvature (bent DNA). This region was replaced with another sequence by using randomly synthesized oligonucleotides. Among the reconstructed plasmids, a plasmid which could endow E. coli cells with the strongest resistance to ampicillin on plates was selected. Nucleotide sequence and DNA conformation of the altered region was investigated. PMID- 1289799 TI - Quantification of the c-myc gene in gastric carcinomas by the triplex polymerase chain reaction and high performance liquid chromatography. AB - The triplex polymerase chain reaction (PCR) and high performance liquid chromatography (HPLC) techniques were used to examine the state of amplification of the c-myc gene in gastric carcinomas. Sequences from the c-myc gene and from the two control genes were coamplified by PCR. The coamplified PCR products were separated and quantified by HPLC and the copy numbers of the c-myc gene were calculated by comparing the peak areas generated by PCR products. Increased copy numbers of the c-myc gene were found in 2 of 5 patients. PMID- 1289800 TI - Efficient cDNA cloning method using solid phase DNA probe. AB - We are now developing a novel and efficient method using solid phase DNA probe to isolate a particular recombinant cDNA from single stranded cDNA library. Target clone coding metapyrocatechase (MPC) and cDNA library constructed from mRNA of U 937 (human lymphoma cell line) were converted to single stranded form by superinfection of helper phage (M13KO7). Probe DNA (25 mer) composed of a portion of the target cDNA was synthesized, attached to an HPLC gel and used as a solid phase DNA probe. Hybridization between probe DNA and target clone was performed in an Eppendorf tube within a few hours. Competent cell (JM109) was transformed with about one-twentieth of hybridized and eluted fraction by Hanahan's method. From the mixture of 1 ng of MPC vector and 5 micrograms of cDNA library, we obtained 50 colonies containing MPC gene out of 63 transformed colonies. PMID- 1289801 TI - Topological alteration of plasmid DNA during cell growth of Escherichia coli. AB - Superhelical alteration of plasmid DNA in Escherichia coli cells was observed during cell growth. Plasmid DNAs were being supercoiled while the cells were actively dividing, and they were partially relaxed after the cultures reached stationary. Unknown structural materials of plasmid DNA which migrated faster than usual superhelices in agarose gel electrophoresis were found among the strains regardless of gyrase genotype. PMID- 1289802 TI - Relationship between the 5'-leader sequence of mRNAs and the translation efficiency in a eukaryotic in vitro system. AB - To examine the effect of the 5'-leader region of mRNAs in regulating translation efficiency, chimeric mRNAs which have various sequences of the 5'-leader were synthesized by the SP6 in vitro transcription system, and translated in the wheat germ in vitro translation system. Translation efficiency was affected by the length of the 5'-leader and the number of the codon A-U-G at the translation initiation site. PMID- 1289803 TI - Tachyplesin I as a model peptide for antiparallel beta-sheet DNA binding motif. AB - In this study, we present a model compound for antiparallel beta-sheet-DNA interaction. Tachyplesin I, cationic antimicrobial peptide, interacts through contacts with the minor groove. Secondary structure of tachyplesin I, antiparallel beta-sheet constrained by two disulfide bridges and connected by beta-turn, contributes significantly to its DNA binding. The present results give valuable information for design of sequence-specific DNA binding peptide based on antiparallel beta-sheet. PMID- 1289804 TI - Interaction of a protooncogene product, Myb with DNAs. AB - The DNA-binding domain of Myb consists of three imperfect tandem repeats and the third one which is essential for sequence-specific binding was established to have a helix-turn-helix-related motif. DNA sequences recognized by Myb have been reported to contain TAACPy sequence. Here we have examined the details of Myb binding sequence. Using DNAs with a single mutation on the various sites of two specific DNAs and some fragments of the DNA-binding domain of Myb, we have found that (i) in a specific DNA which contains only one AAC sequence, each AAC nucleotide is found to be essential for the specific binding of Myb, while any other mutations cause no serious binding loss, (ii) in a specific DNA which contains two AAC sequences separately, one AAC is not so important in the binding, and (iii) for the specific binding with DNA, at least both repeats 2 and 3 of Myb are required. These findings suggest that repeat 3 containing a helix turn-helix-related structure recognizes the core AAC sequence and repeat 2 supports this recognition by interactions with phosphate groups of DNA. PMID- 1289805 TI - Effects of base damages on DNA replication--mechanism of preferential purine nucleotide insertion opposite abasic site in template DNA. AB - DNA polymerase preferentially inserts purine nucleotides opposite non-instructive lesions such as abasic sites during DNA replication. In order to elucidate the mechanism of the preferential insertion, a DNA template containing a model abasic site and primers containing 4 different nucleotides (A,G,C,T) at primer terminus were synthesized. The stability of the primer terminus nucleotide placed opposite the abasic site was evaluated on the basis of its sensitivity to 3'-5' exonuclease associated with DNA polymerase. PMID- 1289806 TI - A study on conformationally restricted sangivamycins and their inhibitory abilities of protein kinases. AB - Conformational restrictions of sangivamycin, a rather selective inhibitor of PKC, could be achieved by the use of the steric effect and the gauche effect of the substituents on the ribofuranose moiety. The conformational deviations obtained by these methods were found to nicely correlate with the inhibitory ability of PKC. PMID- 1289807 TI - On the base sequence of the promoter of Alzheimer's disease amyloid A4 precursor gene in transcription initiation. AB - The base sequence of a specific DNA region of the APP gene identified as the promoter was analyzed by means of the quantity Sr corresponding to superdelocalizability of oxygen ion of each phosphate for the ten DNA dimer units (XY/Y' X') and the six [(XY/Y'X')+H+] complexes. The base sequence of the -35 signal was determined to be 5'-CAGCTG-3' (-49 to -44). On the other hand, the base sequence of the -10 signal was found several ones. Therefore, transcription is to initiate at multiple sites. The mechanisum how RNA polymerases can recognize each transcription site, was proposed. The result explains fairly well some characteristics of the promoter of the APP gene experimentally found so far. PMID- 1289808 TI - Recognition and structural perturbation of GC box DNA by Sp1 zinc finger. AB - Interaction of Sp1 with GC box DNA was investigated by several footprinting experiments. Methylation of four guanine bases is strongly protected by Sp1 binding, while one guanine base in GC box is extremely hypermethylated. Sp1 binding also induces new cleavage at 5'-GA-3' site within GC box by bleomycin iron complex. PMID- 1289809 TI - Mutations induced by DNA lesions in hot spots of the c-Ha-ras gene. AB - In order to investigate whether several DNA lesions (O6-methylguanine, 8 hydroxyguanine, xanthine, an abasic site analogue and hypoxanthine) activate a c Ha-ras gene and to determine the type of mutations induced by the DNA lesions, they were introduced into a synthetic c-Ha-ras gene by DNA cassette mutagenesis techniques. The modified genes were transfected into mouse NIH3T3 cells and the c Ha-ras genes present in transformed cells were analysed. O6-methylguanine and xanthine induced a mutation to A, hypoxanthine induced a mutation to G. 8 hydroxyguanine and the abasic site analogue caused random mutations in the modified and adjacent positions. These results indicated that the synthetic c-Ha ras gene is very useful for the detection of mutations caused by a DNA lesion. PMID- 1289810 TI - Photosensitized formation of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in DNA by riboflavin. AB - Potosensitized formation of 8-hydroxyguanine in DNA by riboflavin was observed. A reaction mechanism involving guanine radical cation and hydration reaction was proposed. This hypothesis was confirmed by the incorporation of [18O]-atom within guanine moiety in isotopic experiments using [18O]-H2O. Photosensitized formation of oh8Gua by riboflavin was also observed in cellular DNA. PMID- 1289811 TI - Post-translational modification of protein by tyrosine sulfation: active sulfate PAPS is the essential substrate for this modification. AB - In vitro tyrosine sulfation of recombinant proteins would be a valuable tool in converting those proteins expressed in prokaryotic vectors to their natural form. For this purpose tyrosylprotein sulfotransferase (TPST), the enzyme responsible for tyrosine sulfation of proteins, was characterized from a bovine liver Golgi preparation. TPST was active in a acidic environment with a pH optimum of 6.25, and displayed a stimulation by the Mn2+, with the optimum activity in the presence of 5mM MnCl2. TPST was able to sulfate recombinant hirudin variant 1 (rHV-1) expressed in Escherichia coli and the C-terminal hirudin fragment 54-65 but not the N-terminal hirudin fragment 1-15 by using 3'-phosphoadenosine 5' phosphosulfate (PAPS), indicating its specificity for the naturally sulfated tyrosine 63. Comparison of the reaction kinetics on synthetic peptides showed that the bovine liver TPST has a higher affinity and reaction rates for those peptides with a aspartyl residue on the N-terminal side of the tyrosine when compared with a glutamyl residue. PMID- 1289812 TI - Some novel pyrimidine nucleoside rearrangements effected by diethylaminosulfur trifluoride (DAST). AB - Pyrimidine nucleosides (or their 5'-aldehydes) when treated with DAST give O2,5' (fluoro)-anhydronucleosides. If this is prevented by blocking N-3 or O4, the desired 5'-deoxy-5'-(di)-fluoronucleoside is accompanied by the production of a compound resulting from migration of the base following scission of the N-1-->C 1' bond and formation of O2-->C-5'. This is a particular example of a much more general phenomenon, seen when suitably substituted ribofuranoses are treated with DAST. PMID- 1289813 TI - Mechanism of protein priming DNA replication of B.subtilis phage M2. AB - B.subtilis phage M2 uses a protein, instead of RNA, as the primer of its DNA replication. Hence this protein encoded in the phage genome is called as the primer protein (PP). At the initiation of DNA replication, a hetero dimer complex with its own DNA polymerase and the PP supposed to interact with the terminal protein (TP), which is covalently bound to the template DNA (TP-DNA). PP contained an important adhesive amino acid sequence, Arg-Gly-Asp (RGD), near the carboxyl terminal. We have recently showed that the synthetic RGD peptide inhibited the transfection of phage M2. By site-directed mutagenesis, we introduced different amino acid into the RGD site of PP. These altered PP decreased obviously the priming activity in vitro. PMID- 1289814 TI - Action of 5-trifluoromethyl-2'-deoxyuridine on DNA synthesis. AB - The action of 5-trifluoromethyl-2'-deoxyuridine (CF3dUrd) on DNA synthesis was investigated in vitro assay systems with purified DNA polymerases. CF3dUrd was incorporated into the DNA of mammalian cells in culture. We studied the incorporation of CF3dUrd 5'-triphosphate (CF3dUTP) into DNA and effect of CF3dUrd residue on DNA synthesis. Therefore, we synthesized oligonucleotides that allow site specific introduction of a CF3dUrd residue into a synthetic DNA oligonucleotide. After CF3dUTP incorporation, the primer was extended for human DNA polymerase alpha (pol. alpha). When CF3dUrd residue was located at an internucleotide site in the template, however, pol. alpha was exhibited a strong arrest band one nucleotide after the CF3dUrd residue site, and Escherichia coli polymerase I (Klenow fragment) also exhibited a weaker arrest band one nucleotide before the CF3dUrd residue. These results suggested that a mechanism of antitumor activity of CF3dUrd is inhibition of DNA replication. PMID- 1289815 TI - Synthesis of chimeric RNAs between U6 small nuclear RNA and (-)sTRSV and analysis of their cleavage activities against the substrate RNA. AB - U6 small nuclear RNA (U6 snRNA) is one of the spliceosomal RNAs essential for pre mRNA splicing. Highly conserved region of U6 snRNA shows a structural similarity with the catalytic center of the negative strand of the satellite RNA of tobacco ring spot virus [(-)sTRSV], supporting the hypothesis that U6 snRNA has a catalytic role in pre-mRNA splicing. To test this hypothesis, we examined in vitro whether synthetic RNAs consisting of the sequence of the highly conserved region of U6 snRNA or various chimeric RNAs between the U6 region and the catalytic center of (-)sTRSV could cleave a substrate RNA that can partially base pair with them and has a GU sequence between the pairing regions. Chimeric RNAs with 70 to 83% sequence identity with the conserved region of S. pombe U6 snRNA cleaved the substrate RNA at the 5' side of the GU sequence. In addition, we found that the highly conserved region of U6 snRNA is similar in structure to the catalytic core region of the group I self-splicing intron in cyanobacteria. These results support the hypothesis that U6 snRNA catalyzes the pre-mRNA splicing reaction and U6 snRNA may originate from the catalytic domain of an ancient self splicing intron. PMID- 1289817 TI - Temperature-gradient DNA probe chromatography of nucleic acids on nonporous supports. AB - Temperature-gradient DNA probe chromatography of nucleic acids on a nonporous support with a homogeneous particle size of 2.5 microns showed a higher base sequence discriminating power and a larger linear capacity than that on a porous support with a larger and less homogeneous particle size. The resolution on the nonporous support was high enough to separate samples with a single-base mismatch of the less destabilizing groups, including G-G and G-T base mismatches, even when it locates very near the end of the probe. PMID- 1289816 TI - Sequence specific block of in vitro DNA synthesis with isopropyl phosphotriesters in template oligodeoxyribonucleotides. AB - We have synthesized four oligodeoxyribonucleotides each bearing an isopropyl phosphotriester at a defined position. These oligomers were used as templates for in vitro DNA synthesis catalyzed by Escherichia coli DNA polymerase I large fragment. Results showed that the phosphotriester inhibits the DNA chain elongation and the level of the inhibition is dependent on the base 5' to the phosphotriester. PMID- 1289818 TI - The formation and enzymatic repair of DNA modifications caused by the haloethylnitrosoureas and related compounds. AB - The haloethylnitrosoureas are both useful antitumor agents and known carcinogens. These biological activities are believed to be associated with DNA modification, and some biologically significant lesions have been identified in DNA exposed to these agents. At the same time, DNA repair is a cause of resistance to treatment by these agents, and may also serve as protection against their carcinogenic effects. PMID- 1289819 TI - DNA hydrolysis by rare-earth metal ions. AB - Plasmid DNA and poly(dA) are cleaved by rare-earth(III) ions at pH 7-8 and 50 degrees C. The cleavage has been confirmed by prompt conversion of supercoiled pBR 322 plasmid DNA (Form I) to a relaxed Form II. Furthermore, degradation of poly(dA) to shorter oligonucleotides is clearly evidenced by HPLC. A possible application of the metal ions (and their complexes) to artificial nucleases is indicated. PMID- 1289820 TI - DNA strand scissions by hydroxamic acids in the presence of Cu(II) ion under aerobic conditions. AB - Carbazolyloxyacetohydroxamic acid (1), 9,9'-decamethylene-bis carbazolyloxyacetohydroxamic acid (2), benzohydroxamic acid (3), and acetohydroxamic acid (4) without reducing agent under aerobic conditions induced DNA strand scissions with increasing activities in the order of 4 > 3 > 2 > 1. The inhibition experiments indicated that hydrogen peroxide and superoxide participated in the reactions, but hydroxyl radical or singlet oxygen did not. PMID- 1289821 TI - Identification of important bases for the self-cleavage activity at two single stranded regions of genomic HDV ribozyme. AB - In order to determine important bases at two single-stranded regions [SSrA (726 731 nt) and SSrB (762-766)] derived mainly from secondary structure models in genomic hepatitis delta virus (HDV) ribozyme possessing self-cleavage activity, we have constructed several point mutants at these two regions on the HDV88 molecule (683-770). Among the bases at SSrA and SSrB regions C763 was found to play an essential role during self-cleavage process since substitutions to any other bases viz. A or G or U completely abolished the activity. PMID- 1289822 TI - Ribozymes for specific inhibition of mRNA function in the nematode Caenorhabditis elegans. AB - Nine different hammerhead ribozymes were designed for three specific sites of unc 22 mRNA in C. elegans, which carry the common catalytic core and 12, 16 or 20 flanking nucleotides for base pairing with the mRNA, and tested for cleavage of short substrate RNA in vitro. All the ribozymes cleaved the substrate RNA catalytically at 37 degrees C and the activities at 37 degrees C were higher for all the ribozymes than those at 20 degrees C, the nematode growth temperature. Plasmids carrying each of a few different promoters and lacZ reporter gene were prepared and tested in the nematode as a test of vectors for the expression of ribozymes in vivo. PMID- 1289823 TI - Cleavage of DNA by viologen related compounds and their incorporation into oligodeoxyribonucleotides. AB - The DNA cleavage reaction by viologen and related compound such as 2,7 diazapyrenium salt was investigated. These viologen analogues were successfully incorporated into the oligothymidylate in the form of covalent bonding at the site of the phosphorous backbone through the linker arm. PMID- 1289824 TI - Recognition of (d(TTTATT) and d(TTATTT) by capillary affinity gel electrophoresis (CAGE) using poly(9-vinyladenine)-polyacrylamide conjugated gel. AB - Sequence-specific recognition of oligodeoxynucleotide isomers (TTTATT and TTATTT) was achieved by using polyacrylamide-poly(9-vinyladenine) conjugated gel filled capillary affinity gel electrophoresis. It was found that the interaction between poly(9-vinyladenine) and the isomers was dependent on the sequential thymidylic acids of them. PMID- 1289825 TI - NMR studies on solution structure of single-stranded oligonucleotides causing line broadening. AB - Unusual line broadening of 1H-NMR lines attributable to the proton (8H) of guanine residues was observed for all tetradeoxyoligonucleotides tested here which have a specific base sequence of dGXXG (X = A or T). For the same samples, line broadening was also obtained in the 31P-NMR spectra. These broadened signals did not become sharp up to 60 degrees C. This unusual spectral phenomenon has been attributed by 2D-NMR and differential NOE to the compact solution structure of the oligonucleotides. PMID- 1289826 TI - Pentacoordinate oxyphosphorane intermediate always exists in aqueous solution. AB - Gas-phase ab initio calculations indicate that dianionic pentacoordinate oxyphosphoranes do not have a kinetically meaningful intermediate. The simplest oxyphosphorane PO5H3(2-) has the least tendency to have a pentacoordinate intermediate. However, it does have a pentacoordinate intermediate when it is solvated with six water molecules. These results support the hypothesis that the phosphoryl transfer reactions take place via pentacoordinate intermediate not only in acidic but also in basic media. PMID- 1289827 TI - Assignments of Raman tensors to Raman bands of nucleic acids: use of a single crystal of adenosine triphosphoric acid and DNA fibers. AB - A polarized laser (488.0 nm) Raman spectroscopic measurement has been made of a single crystal of adenosine triphosphoric acid trihydrate (ATP.3H2O), whose space group is P2(1)2(1)2(1), and whose dimensions are about 10 microns x 100 microns x 100 microns along the crystallographic a, b and c axes, respectively. For each Raman band in the 300-1800 cm-1 range, relative scattering intensities, Ibb and Icc, which correspond to the bb and cc components of the Raman tensor of the crystal, have been determined. In an aqueous solution of ATP, the depolarization ratio of each Raman band has also been determined. On the basis of these experimental results, some discussions are given of the shapes and orientations of the Raman scattering tensors localized in the base residue, ribose portion, and phosphodiester portions. A similar type of study has been made with a few DNA fibers. PMID- 1289828 TI - Dynamical conformational change of DNA induced by synthetic polymers: direct observation by fluorescence microscopy. AB - Brownian motion and Higher-order structure of DNA molecules complexed with synthetic polymers: poly-L-arginine (pArg) and polyacrylamide (pAAm), were observed using fluorescence microscopy. Quantitative analyses of the conformation and motion of the complexes demonstrate that these two polymers influence the structure of DNA molecules in an opposite way. The electrostatic binding of pArg induces contraction of DNA, whereas the intercalative pseudo-grafting of pAAm extends DNA. PMID- 1289829 TI - Photochemical deoxyribose C2' oxidation in 5-iodouracil-containing hexanucleotide. AB - To investigate photochemistry of 5-iodouracil (IU) in DNA, photoreaction of IU containing oligonucleotides was examined. It was found that d(GCAIU G C) 2 undergoes selective photochemical C1' and C2' oxidation at the 5' side of IU residue to provide ribonolactone-containing hexamer 1 and erythrose-containing hexamer 2. Upon heating under alkaline conditions, erythrose-containing hexamer 2 was found to undergo retro aldol condensation to provide two fragments having glycolaldehyde termini. PMID- 1289830 TI - Interaction of novel tris-intercalators with DNA. Spectrofluorometric studies. AB - Novel DNA binding ligands (1 and its stereoisomer 2) which contain three potentially intercalating units in a linear molecular skeleton were prepared. From a study of the displacement of ethidium bromide from several natural and synthetic polynucleotides, both compounds 1 and 2 were found to show an AT base pair preference in the interaction with DNAs with 2 a slightly higher affinity for DNA. This result is in sharp contrast to that for acridine and anthraquinone, because these two compounds exhibit a GC-preference. PMID- 1289831 TI - Electronic interaction between 3'-azido-2'-deoxythymidine and nucleic acid bases by fluorescence spectroscopy. AB - The ultraviolet (UV) absorption and fluorescence nature of the mixtures of 3' azido-3'-deoxythymidine (AZT), poly 1, N6-ethenoadenylic acid (poly, epsilon A) and mixtures of AZT and poly A (AZT+poly epsilon A) at various molar ratio has been studied. On the basis of the present results, it may be concluded that the azide group of AZT (N6', N7', and/or N8') may link to the phosphate groups of polynucleotide. Thus, results obtained suggest that there are electronic interaction between thymine and ethenoadenine lings at the first excited singlet state. PMID- 1289832 TI - Preparation of thianucleoside derivatives. AB - 1'-Deoxy-4'-thioribonucleoside 1 was synthesized from acyclic allylic alcohol 2 by 8 steps. TMSOTf and SnCl4 were found to be a good mediator for the key coupling of thiafuranose part with pyrimidine base to give beta-isomer preferentially. PMID- 1289833 TI - Introduction of fluorine into the sugar moiety of nucleoside using diethylaminosulfur trifluoride (DAST). PMID- 1289834 TI - Highly stereoselective synthesis of (2'R)-[2'-2H]-deoxyribonucleosides and synthesis of their oligonucleotides. AB - Highly stereoselective synthesis of (2'R)-[2'-2H]-2'-deoxyribonucleosides (2'R:2'S = > 99:1) were accomplished by treating 2'-bromo-3',5'-O-TPDS-2' deoxyribonucleosides with tributyltin deuteride at lower temperatures such as -60 degrees C in the presence of triethylborane. Moreover, synthesis of some oligodeoxyribonucleosides involving them will be described. PMID- 1289835 TI - High pressure mediated Diels-Alder reaction using 2-iminomalonates as dienophiles: novel synthesis of carbocyclic nucleosides. AB - 9-[c-4-(1,2-Dihydroxyethyl)cyclopent-2-en-r-1-yl]-9H-adenine , an isomer of BCA, has been synthesized from Diels-Alder adducts prepared by the reaction of 2 iminomalonates with cyclopentadiene under high pressure. The synthetic method involves a novel C-N bond cleavage reaction by NaBH4-K2CO3 (RRA reaction conditions) and has wide applicability for the synthesis of various carbocyclic nucleosides. PMID- 1289836 TI - Synthesis of 3'-substituted-2',3'-deoxy-2'-methylidenepyrimidine nucleosides. AB - 2'-deoxy-2'-methylideneuridine derivative 9 was converted into 2',3'-didehydro 2',3'-dideoxy-2'-phenyl-selenomethyl derivative 16, which was treated with NCS and tert-butyl carbamate to afford 3'-amino derivative 18 via a [2,3]-sigmatropic rearrangement. Treatment of 9 with DAST gave a mixture of 2',3'-didehydro-2', 3' dideoxy-2'-fluoromethyl derivative 19 and 3'-"up"-fluoro-2'-methylidene derivative 20 in a ratio of 1.5 : 1. On the other hand, when 12 was treated with DAST, 19 and 3'-"down"-fluoro-2'-methylidene derivative 21 were obtained in a ratio of 1 : 1.6. These nucleosides were converted into the corresponding cytidine derivatives 4, 6, and 8, respectively. The reaction mechanisms as well as biological activity of these compounds will also be discussed. PMID- 1289837 TI - Stereoselective synthesis of 4'-carbon-substituted 2',3'-didehydro-2',3' dideoxynucleosides. PMID- 1289838 TI - A simple and convenient method for acyclonucleoside synthesis. AB - Introduction of acyclic chain for synthesis of acyclonucleoside derivatives was achieved in a simple and convenient way. Silylated pyrimidine or purine bases were treated with 1,3-dioxolane, trimethyl chlorosilane and metal iodide, such as KI and NaI, all together at room temperature. By this method, 2-thiopyrimidine derivatives were also obtained in good yield, using 2 molecular equivalents of 1,3-dioxolane. PMID- 1289839 TI - Alkylation reaction of phosphorus oxyacids. AB - Alkylation reactions of phosphorus oxyacids (i.e. phosphoric acid, phosphorous acid, hypophosphorous acid) were examined by means of several methods for the synthesis of the corresponding esters. These reactions were applied to the synthesis of oligonucleotide having phosphotriester bond or phosphonate diester bond. PMID- 1289840 TI - Synthesis and properties of adenosine 6-N-phosphoramidate. PMID- 1289841 TI - Synthesis of sialic acid-containing nucleotide sugars: CMP-sialic acid analogs. AB - Syntheses of some sialic acid-containing nucleotide sugars are reported. The reaction of methyl[(2-hydroxy)ethyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5 dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosid]onate (4) with various fully protected hydrogen phosphonates of nucleotides (5a-c) in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride (TPS-Cl), gave, after oxidation and deprotection, the corresponding sialic acid-containing nucleotide sugar analogs (8a-c). PMID- 1289842 TI - Syntheses of oligonucleotide derivatives with P(V) porphyrin and their properties. AB - Two types of oligonucleotide derivatives which are substituted by P(V) porphyrin at the phosphorus atom of an internucleotidic linkage and at the 5'-terminal internucleotidic linkage via a spacer were synthesized (Fig. 1), and hybridization capabilities of them with complementary oligonucleotides were evaluated. A novel method for a sensing of oligonucleotide by the fluorescence quenching via photo-induced electron transfer between the P(V) porphyrin labeled oligonucleotide and pyrene-labeled one on the oligonucleotide template is reported. PMID- 1289844 TI - A mother's nightmare. PMID- 1289843 TI - Fluorescent dye phosphoramidite labelling of oligonucleotides. AB - A series of fluorescein phosphoramidites (FAM) have been synthesized for use on automated DNA synthesizers. After coupling of the FAM reagents to the 5' hydroxyl of the oligonucleotide on the DNA synthesizer, the excess reagent is removed by washing the solid support. The dye, and its linkage to the oligonucleotide, are stable during the conditions of DNA synthesis and cleavage/deprotection conditions. Purification is attained with the OPC (Oligonucleotide Purification Cartridge), a polystyrene based affinity matrix, which selectively retains hydrophobic oligonucleotide conjugates. Analysis by MicroGel capillary electrophoresis effectively separates fluorescent dye labelled oligonucleotides from unlabelled products. PMID- 1289845 TI - Grade consternation. PMID- 1289846 TI - NHS 93--outlook: unsettled. PMID- 1289847 TI - Phobias. PMID- 1289849 TI - Barred exit. Care study. PMID- 1289848 TI - In a panic. PMID- 1289850 TI - A sick joke. Sexual harassment. PMID- 1289851 TI - Counter-attack. Sexual harassment. PMID- 1289852 TI - Management--forward planning. PMID- 1289853 TI - Team nursing. PMID- 1289854 TI - Songs of praise. PMID- 1289855 TI - Overcoming resistance. Mind your back. PMID- 1289857 TI - HIV tests need time and funds. PMID- 1289856 TI - Education--under debate. PMID- 1289858 TI - Travels of my aunt--history. PMID- 1289859 TI - Accident and Emergency. A private disaster--bereavement. PMID- 1289860 TI - Accident and Emergency. Relative comfort--bereavement. PMID- 1289861 TI - Tenure: for a lifetime? PMID- 1289862 TI - Strength characteristics of glass-ionomer cements. AB - The purpose of this investigation was to compare the compressive and diametral tensile strengths of two silver-reinforced and three conventional glass-ionomer cements of different powder-to-liquid ratios at 1 and 24 hours. ANOVA (P < 0.001) and Tukey's Studentized Multiple Range Test indicated significant differences between the compressive strengths of several of the cements tested (P < 0.05). No significant differences were noted between any of the cements for the diametral tensile strength test (alpha = 0.05). PMID- 1289863 TI - The effect of eugenol-containing and eugenol-free temporary cements on microleakage in resin bonded restorations. AB - Eugenol is known to have a detrimental effect on both composite resin and dentin bonding agents. The purpose of this in vitro investigation was to compare the microleakage among groups of resin-luted inlays when the cavity preparations were pretreated with a eugenol-containing temporary cement, a eugenol-free temporary cement, or no temporary cement. Class 5 inlay preparations (20 per group) were completed in extracted human molars. Following the fabrication of composite resin inlays, the preparations were filled with either a eugenol-based temporary cement, a eugenol-free temporary cement, or no cement. After removal of the cement from the cavity preparations and application of a dentin bonding agent, the composite inlays were luted with a resin cement, thermocycled, stained, sectioned, and evaluated for microleakage under a stereomicroscope. None of the groups exhibited significant leakage at the enamel margins. Both of the groups treated with temporary cement leaked at the nonenamel margins significantly more than the control (no cement) group. No significant difference in leakage was demonstrated between the groups treated with the eugenol-containing and the eugenol-free temporary cements. PMID- 1289864 TI - Carbamide peroxide bleaching: effects on enamel surface hardness and bonding. AB - Three 10% carbamide peroxide home bleaching agents were evaluated to determine their effects on tensile bond strength of resin to enamel and enamel surface hardness. Eighty extracted bicuspid crowns were divided into four groups (three bleaching agents and control), and treated with the bleaching agents for five consecutive days. A bonding site on the buccal surface of each crown was etched with phosphoric acid and an orthodontic bracket bonded in place. The specimens were thermocycled and loaded to failure in an Instron Universal Testing Machine. Five hardness specimens per group were measured prebleaching and after five days' exposure. Analysis by one-way ANOVA indicated no significant differences in bond strength between the four groups (P > 0.05). There were also no differences in pre- or postbleaching Knoop hardness values for the four groups (P > 0.05). This study indicated that in short-term regimens 10% carbamide peroxide does not significantly affect enamel surface hardness or bonding ability. PMID- 1289866 TI - The influence of matrix use on microleakage in Class 5 glass-ionomer restorations. AB - This in vitro study examined the relationship of matrix use to microleakage in class 5 Ketal-Fil glass-ionomer restorations. Class 5 glass-ionomer restorations were placed on the facial and lingual surfaces of 40 extracted human molars. The occlusal margin was located on enamel, and the cervical margin was located on cementum or dentin. Each tooth had one restoration placed with and without the aid of a soft metal matrix. Specimens were thermocycled (1234 cycles, 6 degrees C -60 degrees C, 30-second dwell time) and immersed in 5% methylene blue dye for four hours. The teeth were sectioned occlusogingivally through the center of each restoration, viewed with an optical microscope (X10), and each restoration was scored for dye penetration around the cavity walls. The enamel and cementum margins were scored separately for the extent of marginal leakage. No difference in leakage was found between restorations placed with or without a matrix (P > 0.05). Enamel restorations leaked significantly less than nonenamel margins, regardless of matrix use (P > 0.05). PMID- 1289865 TI - The effect of incremental versus bulk fill techniques on the microleakage of composite resin using a glass-ionomer liner. AB - Incremental placement of composite resin has been suggested to reduce microleakage, particularly at the gingival margin of class 5 cervical restorations. It has become clinically advantageous to place a glass-ionomer liner over dentin to further minimize microleakage resulting from a bond between the dentin and glass ionomer, and glass ionomer and resin. The objective of this study was to compare the microleakage behavior of three hybrid composite/bonding agent systems using bulk and incremental filling techniques utilizing a glass ionomer liner. This was accomplished in vitro using freshly extracted bovine incisors and a Ca45 radioisotope and autoradiography. Sixty bovine incisors were divided into six experimental groups of 10 specimens per group. Class 5 preparations were cut at the cementoenamel junction and restored with the appropriate combination of Herculite XR/Bondlite, P50/Scotchbond 2, or Pertac Hybrid/Pertac Bond. All teeth were lined with the glass ionomer Ketac Bond before the final restoration was placed. The samples were finished and stored for 24 hours in distilled water before thermocycling. The samples were tested for microleakage using a Ca45 radioisotope technique and autoradiography. Incisal (enamel) and gingival (dentin) margins were scored separately for microleakage but grouped for statistical analysis. Results were analyzed using the Kruskal Wallis H test. Pertac Hybrid exhibited more leakage than Herculite XR or P50. The difference between microleakage of bulk and incremental filling techniques was only significant for P50. PMID- 1289867 TI - Effect of admixed indium on the clinical success of amalgam restorations. AB - The purpose of this study was to clinically evaluate two formulations of a dispersed-phase, high-copper dental amalgam alloy (Indisperse), which contained admixed indium. One alloy tested contained 5% indium, and the second alloy contained 10% indium. A similar alloy without indium, Dispersalloy, was also placed for comparison. Over the course of the five-year study, there were no differences clinically or statistically regarding texture and luster. The margins of the restorations containing indium incurred slightly less fracture than the non-indium-containing restorations; however, these differences were not clinically significant. It can be concluded that the admixture of 5-10% indium as well as the increased ratio of eutectic spheres to lathe-cut particles found in the indium alloys enhance the clinical performance of amalgam restorations. PMID- 1289868 TI - Award of excellence. PMID- 1289869 TI - Pediatric pharmacokinetics and therapeutic drug monitoring. AB - Recent advances in pediatric clinical pharmacology have provided a more rational approach to using several medications in children. An increased understanding of the effect of human development, concurrent medications, organ function, and disease states on the absorption, distribution, metabolism, and excretion of drugs has provided a stronger scientific basis for determining drug dosages in children. By measuring drug concentrations and utilizing pharmacokinetic and pharmacodynamic principles, the probability of therapeutic response can be enhanced for a number of medications. Likewise, therapeutic drug monitoring can minimize the risk of adverse effects from many drugs used in children. However, it must be recognized that toxicity can occur in some patients even though plasma drug concentrations are in the therapeutic range; similarly, some patients may not experience a therapeutic effect when plasma drug concentrations are in the same target range. Therefore, achieving the desired plasma concentration of a drug can enhance both the probability of a therapeutic response and diminish the probability of a toxic response. Therapeutic ranges, however, are only intermediate endpoints that must be used in the context of additional criteria to assess the clinical efficacy of any given drug therapy. PMID- 1289870 TI - Pediatric ocular injuries. PMID- 1289871 TI - Knee and ankle injuries in children. PMID- 1289872 TI - Index of suspicion. Case 1. Diagnosis: Klinefelter syndrome. PMID- 1289873 TI - Index of suspicion. Case 2. Diagnosis: Addison disease. PMID- 1289874 TI - Index of suspicion. Case 3. Diagnosis: neonatal group B streptococcal sepsis and pneumonia. PMID- 1289875 TI - [The effectiveness of working with dispensary contingents in a rural district epidemiologically unfavorable for tuberculosis]. PMID- 1289876 TI - [The effect of an unfavorable epizootic situation on the basic epidemiological indices for tuberculosis]. AB - Analysis is given of the basis of epidemiological parameters in two districts of the Novosibirsk region, depending on the duration of the unfavourable epizootic situation. Subjects with extensive residual changes were registered 10 times as often in the district with the unfavourable epizootic situation as in the district with fresh tuberculosis outbreak in animals. Studies of infectivity among children and adolescents at the height of tuberculosis outbreak in animals showed that reversion was established in 8.6%, while the share of children with hyperergic reactions increased by 4 times and exceeded the average regional index by 8 times. Children and adolescents from the district with the unfavourable situation for tuberculosis had a low level of reversion (0.3%), but the level of infectivity in children of the decreed ages was high. The complex of health improvement, prophylactic and veterinary measures has been suggested. PMID- 1289877 TI - [The structure of newly detected tuberculosis in persons confined to correctional work institutions]. AB - Tuberculosis morbidity in penitentiary-labour establishments (PLE) is scores of times higher than that among the population on the formation of which it has an influence. Study of the epidemiologic process patterns in PLE and specific features of tuberculosis in convicts is a necessary condition for the development of effective antituberculous measures. Analysis of the structure of newly diagnosed tuberculosis in convicts has demonstrated that tuberculosis prevailed among subjects aged 30 years (49.2%) and in those at the age of 30-39 years (38.4%). The clinical structure is predominated by infiltrative (57.4%) and focal (36.4%) forms, while fibrocavernous and cirrhotic forms are absent. The organization of measures aimed at the timely detection of tuberculosis in convicts was found to have a number of defects, which contribute to tuberculous infection spread among subjects staying in PLE. PMID- 1289878 TI - [The organization and efficacy of the hospital treatment of patients with newly detected pulmonary tuberculosis in Siberia]. AB - Analysis of the clinical observations of 2049 patients with newly diagnosed pulmonary tuberculosis has demonstrated that 54.3% of them had the destructive phase, 52.2% bacilli excretion, 20.7% the neglected forms, and 64.3% attendant diseases. The absence of bacilli was found in 82% of the patients with the destructive forms (in 5 months' period after hospitalization), and elimination of caverns in 74.5%. The most serious defects were found in the organization of a diagnostic and therapeutic process. The complex of measures has been suggested to promote heightening of treatment effectiveness in newly detected patients at the hospital stage. PMID- 1289879 TI - [Primary disability as a consequence of tuberculosis and the factors that contribute to its development]. AB - Analysis is given of a high level of invalidity in 508 patients in four regions to whom invalidity due to tuberculosis was first established in 1987-1989. The main factors responsible for invalidity included progress of a tuberculous process, ineffective chemotherapy, untimely diagnosis, the presence of serious attendant diseases, functional disorders of the affected organs, complication of the disease, asocial way of life (chronic alcoholism, narcomania), and insufficient material provision of large families. Most invalids had a combination of the above factors. PMID- 1289880 TI - [Primary disability in patients with tuberculous spondylitis and the ways for its decrease]. AB - Causes responsible for invalidity were analysed in 167 patients with a circumscribed form of tuberculous spondylitis. The causes were divided into 4 groups: diagnostic errors; errors in treatment; prognostic errors (late indications to surgical treatment); organizational errors. Heightening of the quality of early diagnosis of tuberculous spondylitis at a primary application to a medical institution and timely high-quality specific therapy in the antituberculous institutions will contribute to an increase in treatment effectiveness and invalidity reduction. PMID- 1289881 TI - [Tuberculosis morbidity in medical workers and the measures for their social protection]. AB - Tuberculosis morbidity among the medical workers has been studied in 39 territories of Russia. It has been established that medical personnel contract tuberculosis much frequently than the population of Russia on the whole. Morbidity is particularly high among the personnel of institutions of the antituberculous service, being 293.3 per 100,000 working subjects. Tuberculosis morbidity is higher among females (78.8%) and in subjects aged before 50 years (81.4%). Success of tuberculosis control among the medical personnel can be provided by actively solving the problems of tuberculosis prevention, including the organization of health improvement measures under conditions of sanatorium and measures aimed at social protection. PMID- 1289882 TI - [Risk factors in the development of pulmonary tuberculosis and the characteristics of its course in people over 50]. AB - Study of the onset and course of pulmonary tuberculosis in 121 patients between the ages of 50 and 75 years showed that 31.4% of the patients belonged to a high risk group of tuberculosis. Study also revealed a high frequency of occurrence of disseminated and fibrocavernous tuberculosis, the predominance of disseminated processes, frequent destruction of lung tissue, massive bacilli excretion and marked clinical manifestations of the disease, which develops in more than half of the patients in the period between the established terms of prophylactic fluorographic examination. PMID- 1289883 TI - [The plastic repair of the residual axillary cavity following the open treatment of a cavern with the tissue from its wall and from the deep subcutaneous fat]. AB - A variant of plastic surgery of the residual cavities after cavernotomy of armpit localization had been elaborated. Cicatricial tissue of the residual cavity wall is preserved and only the upper part of the residual cavity wall is used in combination with deeply-lying fatty tissue of the axillary fossa. Plastic closure of the residual armpit cavities after open treatment was successfully performed in 27 patients. The necessary condition for this operation performance is cessation of excretion of bacilli, sputum and discharge from the residual cavity on condition that the patient is in a satisfactory condition. PMID- 1289884 TI - [The importance of thoracostomy in treating pleural empyema with bronchial fistulae in patients with pulmonary tuberculosis]. AB - In contrast to the nonspecific pleural empyemas, which are managed effectively by closed methods of debridement, management of patients with tuberculous pleural empyema and bronchial fistulas requires early application of thoracostoma, which allows cavity debridement, long-term antituberculous chemotherapy and preparation to radical surgery. This was confirmed by the comparative analysis of the results of radical operations after closed and open methods of management of empyema cavity in 139 patients. The site of thoracostoma application is determined by the location and size of an abscess and the forthcoming radical operation. Long action bandages with chlorhexidine bigluconate and ultraviolet radiation are prescribed for the debridement of open pleural empyemas. PMID- 1289885 TI - [The solitary tuberculoma as a "mask" of a lung tumor]. AB - The results are given of the clinical and X-ray examination of 56 patients who underwent surgery for granuloma which had the course of a "masked" blastoma. Taking into consideration the objective difficulties encountered in differential diagnosis, measures must be taken to perform the intraoperative express diagnosis which will help to avoid tactical errors in relation to the volume of surgical intervention. PMID- 1289886 TI - [The use of plasmapheresis in treating the broncho-obstructive syndrome in patients with pulmonary tuberculosis]. AB - Examination included 81 patients with the broncho-obstructive syndrome, which in 45 patients was combined with active pulmonary tuberculosis. Plasmapheresis was used in 43 patients. Treatment proved to be effective in patients suffering from bronchial asthma who underwent plasmapheresis; attacks fully discontinued in 70.9 x 8.15 patients. Plasmapheresis had no unfavourable influence on the specific process, it promoted fuller restoration of external respiration parameters and reduction of the level of acute-phase proteins. PMID- 1289887 TI - [The tuberculosis control work of a general medical network under the conditions of budgetary insurance medicine]. AB - The first results are given of the elaboration of the specific features of antituberculous measures control in the general medical network under conditions of the budget-insurance medicine. The clinico-economic standards have been compiled, which are the obligatory programs of actions of medical prophylactic establishments as well as the required final results (quality standards). Systematization of the tasks of antituberculous work and methods of their solution for feldsher's station is presented as an example. A characteristic is given to the approaches to quality standards compilation A preliminary determination of a necessary volume of knowledge concerning tuberculosis is given as well as the list of the practical skills that a general practitioner should master. The documents elaborated make the basis for the medico-prophylactic establishments to be accredited, for certification of doctors and the evaluation of their work by the insurance companies. PMID- 1289888 TI - [Tele-electrometry of the respiratory musculature in healthy subjects and patients with obstructive ling diseases]. AB - Respiratory muscles fatigue is a common symptom typical for chronic obstructive pulmonary diseases. The authors were the first to use an original diagnostic system of distant electrometry "Briz-1" and examination techniques. The principle of the diagnostic system operation is based on a contactless measurement of magnitudes of trunk surface excursions during respiratory movements with the help of a system of electromagnetic field transducers located near the trunk. The electromagnetic field is induced by a special generator. Examination included 75 patients with chronic obstructive pulmonary diseases and 21 healthy volunteers (the norm has been elaborated). The results obtained on the diagnostic system were compared with the clinico-functional studies. The method is simple, harmless, easy for patients in terms of load, informative and allows numerous measurements. Diagnostic criteria of obstructive pulmonary diseases and diaphragm fatigue have been developed. PMID- 1289889 TI - [The assessment of bronchial patency by conducting broncholytic and loading tests in patients with pulmonary pathology]. AB - Reproducibility of the parameters of bronchial patency was studied in 31 patients with nonspecific pulmonary diseases, changes in the parameters of bronchial patency during the berotek and loading tests--in 28 healthy subjects, the dynamics of bronchial patency in these tests and the value of separate methods of study of bronchial patency--in 119 patients with active pulmonary tuberculosis. The parameters of spirography, forced expiration flow-volume and general plethysmography were used. Assessment of the results of the pharmacological and loading tests require consideration of reproducibility of the parameters and their changes in healthy subjects in connection with a broncholytic action on the tone of bronchial muscles. The table of limited diagnostically insignificant functional changes in bronchial patency in given. When evaluating the results of functional tests, it is expedient to use a combination of the parameters of spirography, the curve of forced expiration flow-volume and general plethysmography and in the choice of method preference should be given to the registration of the curve of forced expiration flow-volume. The most sensitive parameters of the dynamics of bronchial patency in the broncholytic and loading tests have been developed. PMID- 1289890 TI - [The validation of the adequacy of chemotherapy in bladder tuberculosis based on a study of bacteriostatic activity]. AB - Study of the bacteriostatic activity (BA) of the blood, urine and tissue of the tuberculosis-affected urinary bladder after the administration of two tuberculostatic combinations (isoniazid + cycloserine and isoniazid + rifampicin) has demonstrated the difference in the BA curves that were formed in the above media. Use of isoniazid + cycloserine gives rise to a high BA level by 6-9 h with further gradual decrease of the parameters. The combination of isoniazid + cycloserine produces a typical double-humped curve with titre prolongation. The data obtained give evidence on the experience of the use of the first combination of the preparations in patients with fresh circumscribed urinary bladder lesions. The second combination (isoniazid + rifampicin) is indicated in the presence of ulcerous-cicatricial changes in association with a more prolonged circulation of the preparations in the organism (specific features of rifampicin metabolism). PMID- 1289891 TI - [The differential diagnosis of tuberculosis and cancer of the lung in the practice of the phthisiologist]. PMID- 1289893 TI - [Abdominal tuberculosis]. PMID- 1289892 TI - [The current characteristics of postprimary forms of adenogenous pulmonary tuberculosis in adults]. PMID- 1289894 TI - [The diagnosis and pharmacological correction of the urodynamic disorders of the upper urinary tract in nephrotuberculosis]. PMID- 1289895 TI - [The early diagnosis of drug allergy by biophysical methods]. PMID- 1289897 TI - [The surgical treatment of secondary aspergillosis of the residual pleuropulmonary cavity following lung resection]. PMID- 1289896 TI - [Experimental models of combined tuberculosis-opisthorchiasis pathology]. AB - An experimental model of the combined course of tuberculosis and opisthorchiasis is presented in the following variants: pulmonary tuberculosis-chronic opisthorchiasis, acute and chronic opisthorchiasis in combination with tuberculosis contamination, BCG and opisthorchiasis. Specific changes in the combined pathology are shown which differ from those that accompany each of the nosological forma. Data obtained in bacteriologic, parasitologic, immunologic and pathomorphologic studies were used to describe characteristic features of the models. The results obtained allow a suggestion that parasitocenosis of mycobacteria and Opisthorchis organisms has an influence on the pathogenesis, clinical picture, diagnosis, treatment, epidemiology and prevention of tuberculosis-opisthorchiasis combined pathology. PMID- 1289898 TI - [Tuberculosis in the rural population as a public health problem during the organizational perestroika of medical care]. AB - The results of 5 years' observation of the epidemiologic situation for tuberculosis in the northwest region of the Russian Federation have shown that tuberculosis prevalence among the rural population is less than in Russia, on the average. There is a tendency towards disappearance of the epidemiologic differences between the rural and urban locality, which enables one to regard tuberculosis as a single epidemiologic problem. At the same time, high level of tuberculosis contingents is maintained in rural settlements, which can be ascribed to the insufficient effectiveness of treatment or dispensary follow-up. A negative influence of social factors also grows. In conditions of the multivariant character of the organization of the public-health service optimization of work can be achieved by the creation of interregional scientific practical centres. PMID- 1289899 TI - [Pulmonary alveolar proteinosis in a patient with silicotuberculosis]. PMID- 1289901 TI - Actin mediated regulation of muscle contraction. AB - Striated and smooth muscles have different mechanisms of regulation of contraction which can be the basis for selective pharmacological alteration of the contractility of these muscle types. The progression in our understanding of the tropomyosin-troponin regulatory system of striated muscle from the early 1970s through the early 1990s is described along with key concepts required for understanding this complex system. This review also examines the recent history of the putative contractile regulatory proteins of smooth muscle, caldesmon and calponin. A contrast is made between the actin linked regulatory systems of striated and smooth muscle. PMID- 1289900 TI - The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation. AB - Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activation for the most potent carcinogenic PAH, whereas monooxygenation to form bay-region diol epoxides is generally a minor pathway. For benzo[a]pyrene and 7,12-dimethylbenz[a]-anthracene, 80% and 99%, respectively, of the DNA adducts formed by rat liver microsomes or in mouse skin arise via the radical cation. Therefore, studies of PAH activation should begin by considering one electron oxidation as the primary mechanism. PMID- 1289902 TI - [Present status on therapy of alcoholism]. PMID- 1289903 TI - [Present status and future of geriatric psychiatry]. PMID- 1289904 TI - [Clinical approach to memory disorders]. PMID- 1289905 TI - [Certification of psychiatry specialists]. PMID- 1289906 TI - [Post-graduated education and certification of psychiatrists]. PMID- 1289907 TI - [Questionnaires of general population for ideal psychiatrists and the certification as a standard opinion]. PMID- 1289908 TI - [Present status and problems of psychiatric certification boards]. PMID- 1289909 TI - [Position of diagnostic imaging in psychiatry]. PMID- 1289910 TI - [Psychiatric diseases of quantitative evaluation by CT scan and problems of the clinical application]. PMID- 1289911 TI - [Morphological study of the brain in patients with schizophrenia by MRI]. PMID- 1289912 TI - [Diagnosis of nerve net disorders in patients with schizophrenia by high resolution SPECT]. PMID- 1289913 TI - [Brain phosphate metabolism in patients with manic-depressive psychosis]. PMID- 1289914 TI - [Diagnostic imaging of dementia by SPECT]. PMID- 1289915 TI - [Brain function analysis by H2 15O-PET--role of left frontal lobe of brain in neural regulation of saccade]. PMID- 1289916 TI - Intensity dependence of auditory evoked potentials and clinical response to prophylactic lithium medication: a replication study. AB - A predictor of clinical response to prophylactic lithium treatment in affective psychoses would be of considerable importance. In a pilot study, responders to prophylactic lithium medication, as compared with nonresponders, were characterized by a steeper slope of the amplitude/stimulus-intensity function (ASF slope) of the N1/P2 component of the auditory evoked potential. We tried to replicate this finding in 34 stabilized outpatients with affective illness who had been treated with lithium for at least 3 years. As in the pilot study, responders were again characterized by steeper ASF slopes than nonresponders. Since a steep ASF slope seems to indicate low central serotonergic function, it is speculated that a steep ASF slope characterizes those patients with a serotonin deficit who respond to serotonin agonists like lithium. PMID- 1289917 TI - Evaluation of a new instrument for the detection of eating disorders in community samples. AB - The aim of this study was to develop and evaluate an instrument to detect the various forms of clinical eating disorder that exist among young women in the community. A subsidiary aim was to test an alternative instrument based directly on the DSM-III-R criteria for eating disorders. Participants were 285 young adult women listed in the case registers of two general practices. Receiver operating characteristic analysis showed that the new (statistically derived) instrument performed well and was better at case identification than the only other instrument currently available. In contrast, the instrument based directly on the DSM-III-R criteria performed poorly. It was not possible to assess the ability of the new instrument to detect cases of anorexia nervosa since there were no cases in the sample. PMID- 1289918 TI - Visual information decoding deficits in schizophrenia. AB - Schizophrenic and control subjects were tested on two-flash fusion (TFF) and visual backward masking (VBM) tasks in a repeated measures design. Each subject was tested in a single session. Both tasks used the same equipment and stimuli. There was no difference between the groups in their ability to detect the presence of two separate stimuli in the TFF task. Schizophrenic subjects did require longer interstimulus intervals (ISI) than control subjects to accurately report one of the two targets in the VBM task. Analysis of individual targets reveals that the VBM deficit is a function of the similarity of the target and mask. The more feature detail discrimination necessary, the longer an ISI is required in VBM. The data are interpreted as supporting the conclusion that since the groups did not differ in their performance of the TFF task, which would also have been affected by a sensory abnormality, the deficit in VBM must be explained by reference to a higher level of information processing. The VBM deficit is a failure to decode the target stimulus, and is not simply a function of abnormalities due to an overactive transient channel system. PMID- 1289919 TI - Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. AB - Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels. PMID- 1289920 TI - Relationship of object loss during development to hypothalamic-pituitary-adrenal axis function during major affective illness later in life. AB - Although many studies have attempted to determine whether early object loss influences the risk of developing major affective illness in adulthood, there are few empirical data relating early loss to subsequent hypothalamic-pituitary adrenal (HPA) axis dysfunction in adulthood. Forty-five psychiatric inpatients admitted for an active major affective illness, all of whom had a previous history of a significant permanent object loss (by death only), were studied retrospectively in this preliminary investigation to examine whether the type and timing of object loss experienced earlier in life would discriminate affectively ill patients who exhibit HPA dysfunction. Several loss variables were found to be statistically significant predictors of cortisol responses following glucocorticoid challenge. A median split of the distribution was used to classify patients into early loss (< or = 19 years) and late loss (> or = 20 years) groups. Analyses for all subjects, early and late loss combined, showed that late loss was associated with higher 11 p.m. cortisol levels. Within the early loss group, however, age of first loss was the most significant predictor of 4 p.m. cortisol levels after dexamethasone challenge. Consistent with the hypothesis that childhood object loss may be associated with long-term alterations in HPA axis function, younger age of loss correlated significantly with higher 4 p.m. cortisol responses. These preliminary data suggest that future prospective investigation of the neurobiological as well as psychosocial consequences of various types of early loss warrant further study. PMID- 1289921 TI - Cortisol response to intramuscular desipramine in patients with major depression and normal control subjects: a replication study. AB - The authors conducted a double-blind study evaluating the cortisol response to 75 mg of desipramine (DMI), administered intramuscularly to 20 patients with major depressive disorder (MDD) and 20 age- and sex-matched normal control subjects. A blunted placebo-corrected cortisol response to DMI was found in MDD patients in comparison with the normal control subjects. Since the behavioral/side effect and pharmacokinetic profiles of DMI were similar for patients with MDD and normal control subjects, these findings suggest that patients with MDD have an underlying biological insensitivity of the hypothalamic-pituitary-adrenal axis to DMI. It is hypothesized that these findings are consistent with a norepinephrine deficit, an alpha 1-adrenergic receptor insensitivity, or both. Further use of DMI as a neuroendocrine probe for the noradrenergic system is indicated. PMID- 1289922 TI - Neuroleptic malignant syndrome: results of a prospective study. AB - The occurrence of neuroleptic malignant syndrome was examined in a prospective study of 335 neuroleptic-treated inpatients. It was not possible to identify a single unequivocal case of neuroleptic malignant syndrome. It appears to be a very rare condition in patients who are judiciously treated with relatively low doses of neuroleptics. The concept of incomplete forms of neuroleptic malignant syndrome could not be supported. PMID- 1289923 TI - Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. AB - A double-blind clinical trial was carried out to evaluate the efficacy of S adenosyl-L-methionine (SAMe) in speeding the onset of action of imipramine (IMI). SAMe is a naturally occurring substance that has been shown to possess antidepressant activity with a rapid mode of onset and minimal side effects. Sixty-three outpatients with moderate to severe depression were included in the study. After an initial 1-week placebo period, only 40 patients entered the active treatment phase. During the first 2 weeks of the trial, half of these patients received 200 mg/day of SAMe intramuscularly, while the other half received placebo. Simultaneously, oral IMI was administered to all patients at a fixed dose of 150 mg/day. The onset of clinical response was determined by evaluating patients every second day. By the end of week 2, the parenteral treatment was suppressed and IMI was adjusted according to individual needs. Depressive symptoms decreased earlier in the patients who were receiving the SAMe IMI combination than in those who were receiving the placebo-IMI combination. PMID- 1289924 TI - The Moses of Freud and the Moses of Schoenberg. On words, idolatry, and psychoanalysis. PMID- 1289925 TI - Some refinements of the separation-individuation concept in light of research on infants. AB - The separation-individuation concept, though clinically useful, has been called into question in a critique based on systematic infant research. While an effective rejoinder to the critique can be offered, the critique plus the rejoinder nonetheless require some modifications of the initial separation individuation concept. Following a summary of the argument, I offer those modifications here. PMID- 1289926 TI - Thinking through the hungry baby. Toward a new pleasure principle. AB - Freud's metapsychological paradigm and his conception of the neonate were closely linked. The vignette of the "hungry baby" epitomizes Freud's pain-centered, pragmatic understanding of primary motivational forces. Within the range of mainstream psychoanalytic theory, this point of view has remained essential, although in recent decades it has been supplemented in important ways by a more object-centered, moral perspective on character development. But psychoanalysis still lacks a positive metapsychological formulation of pleasure as a motivation in its own right. This paper explores the problem in the light of recent infant research and of Hartmann's systematic reflections on metapsychology. PMID- 1289927 TI - On narcissistic defenses. PMID- 1289928 TI - Did Dora have an oedipus complex? A reexamination of the theoretical context of Freud's "fragment of an analysis". AB - A careful review of the Dora case refutes the commonly held view that it reflects Freud's adoption of his classical oedipal model. Through Dora, Freud examined some of the theoretical and emotional underpinnings of the seduction theory and began a complex and very gradual move toward an oedipal model, never reaching his classical formulation. The transitional nature of this case allows for an understanding of some of Freud's difficulties in adopting the oedipal model and the considerations that, nevertheless, eventually determined the move. How and why this was overlooked in all later studies of the case has important implications for the process of development of psychoanalytic theory and the writing of its history. PMID- 1289929 TI - Attachment and separateness. A theoretical context for the integration of object relations theory with self psychology. AB - The aims of attachment and of separateness, and their experiential counterparts within the overall sense of self identity, guide the individual throughout the life cycle. Multiple forms of relatedness, based on varying degrees of self object differentiation and instinctual drive involvement, enable the individual to establish and consolidate a sense of self both as a cohesive and autonomous entity and as inherently attached to others through loving relationships. This theoretical orientation provides a context for integrating Kohut's major conceptual contribution with classical object relations theory. The essence of this integration requires resolution of the challenges that Kohut's concept of "self-object" poses to conventional understanding of the relationship between relatedness and self development. PMID- 1289930 TI - Winnicott's antitheory and Winnicott's art. His significance for adult analysis. AB - The significance of Winnicott's work for the theory and practice of adult analysis is examined. Winnicott's most valuable contribution was to discern important new clinical phenomena. This is a crucial aspect of theory development, but not the same as explicating new theory, and partly accounts for the difficulty integrating his ideas with traditional psychoanalytic theory. Winnicott left the theoretical revisions possibly necessitated by his discoveries for others to accomplish, and some of this new work is discussed and synthesized. The nature of Winnicott's discoveries, especially the phenomenological field of transitional or intermediate experience, is elusive to define, and is also related to his clinical stance and his attitudes to theory for the purposes of clinical work. His work demonstrates the limits of theorizing and of our theories, and also an attitude toward theory that facilitates clinical and theoretical progress. He also provides conceptual language to discuss what is often called the art of psychoanalysis. Both the value and limitations of studying Winnicott are considered. PMID- 1289931 TI - What does psychoanalysis have to contribute to the understanding of character? AB - While character is an indispensable term in psychoanalytic discourse, it is not primarily a psychoanalytic term. The psychoanalytic theories of neurosis and development are built around the idea of the "complementary series." While psychoanalysis has powerful theories about the "accidental" complement, it only recognizes the "constitutional" complement, and psychoanalysis has nothing to say about it. Current research may shed more light on this latter component and also provide the data for future psychoanalytic theorizing about character and personality. PMID- 1289932 TI - The development of a capacity for imagination in early childhood. AB - Imagination as a mental capacity is part of a line of development that begins in the earliest symbiotic interactions between mother and infant, takes further shape as the child moves from dyadic to triadic relations, and culminates in a fully mature capacity to reflect upon in thought one's wishes and feelings vis-a vis multiple others. Particularly for the 3- to 5-year-old child, imagination represents a special mode of mental functioning which allows him to expand his internal object world, motivates him toward increasingly complex relationships with others, and is a central precondition for the creation of the self-defining fantasies characteristic of the oedipal phase. The central neurocognitive precondition for an imaginative capacity is the ability to distinguish thought from action and understand that others as well as oneself are motivated to act because of mental states such as feelings, beliefs, and fantasies. In this paper, we present a view of imagination that integrates observations from psychoanalytically informed studies of the emergence of fantasy play in the oedipal phase with findings from recent work on how children acquire an understanding of their own and others' mental processes. PMID- 1289933 TI - Maturational and experiential components of character formation. AB - This paper explores the concept of character from the point of view of its use both in everyday language and in psychoanalytic literature. It also examines, with clinical illustrations, some of the complex interactions of maturation and experience in the formation of character. PMID- 1289934 TI - Confronting dilemmas in the study of character. AB - Distinctive dilemmas in the psychoanalytic study of character are described. What they are and how they have been addressed illuminate the past achievements and some of the future directions of clinical research. PMID- 1289935 TI - Narcissistic disorders in children. AB - This paper discusses children who initially may seem suitable for psychoanalytically oriented treatment but who do not respond in the anticipated manner. Such difficulties in treatment may suggest the presence of a narcissistic disorder. Clinical material from a latency-aged girl is presented to demonstrate the typical difficulties encountered in maintaining a working relationship with such children, and the special frustrations and countertransference issues that are apt to arise. A set of criteria is proposed to help in the diagnosis of a narcissistic disorder, and a treatment approach is suggested. PMID- 1289936 TI - Rescue fantasies and the secret benefactor. AB - The concept of rescue fantasies is traced from Freud's earliest idea of the rescue of the mother as the fallen woman to later ideas of ambivalent rescue of the father, siblings, and children. Clinical vignettes from work with children and adults illustrate these points as well as reparative rescue fantasies in response to trauma and narcissistic hurt. The contemporary family romance myth of the secret benefactor as rescuer is described. An analytic case presentation explores the narcissistic-masochistic and the positive and negative oedipal meanings of the secret benefactor rescue fantasy. Application to countertransference enactments in the analyst is suggested. PMID- 1289937 TI - The boy from outer space. An exploration of psychotic catastrophe. AB - This is an account of the initial stages in the analysis of Morton, a latency-age boy. Morton is an unusually interesting case for the exploration of fantasy, to which "we must look for the study of early mental phenomena because phantasy is the lingua franca of that period" (Grotstein, 1977, p. 412). PMID- 1289938 TI - The function of humor in a four-year-old. AB - A child's attempt at humor in the midst of a psychoanalytic session is examined. A joke is told that began as a dream which the 4-year-old analysand attempted to modify. The joke is not entirely successful from a formal standpoint. This "failure" is examined from the point of view of the anxiety that may have derailed the joke and the developmental immaturity that may have compromised it. A developmental line of the symbolic process is suggested, double meanings and multiple meanings becoming more complex as development proceeds. PMID- 1289939 TI - Transformations of transference. AB - Transference can be understood to have complementary aspects: the experience in the here-and-now of the relationship with the analyst and the repetition of old relationships. The concept of an enactment is proposed to describe the vivid reexperience of childhood relationships in the here-and-now of the analytic relationship. Countertransference contributions to the enactment are discussed. Transference transformation results from the juxtaposition of the regressive transference enactment and transference experiences that are new and novel to the patient. The analyst can promote such changes by his interpretation of resistances both to the reexperience of the transference repetition and to awareness of the new and novel elements that spontaneously appear in the relationship with the analyst. PMID- 1289940 TI - The moment of recognition. Rabbinic discourse, infancy, and psychoanalysis. AB - Professionals and educated laymen agree that the past 30 years have brought about a revolution in our understanding of infant development during the very first months of life. The inchoate "blooming buzzing confusion" once felt to characterize the neonate has given way to a well-documented realm of finely tuned perceptions and highly complex interactions. These shifts in our thinking are generally assumed to imply that periods chronologically more remote from our own are conceptually more remote from our modern achievements. But in fact, they are not. I here examine ancient and medieval rabbinic texts and find these "modern" issues discussed. The formulations of these texts, I suggest, sharpen the psychoanalytic focus on the role of the integrative function in very early development. PMID- 1289941 TI - Some psychoanalytic implications of Chinese philosophy and child-rearing practices. AB - An examination of Chinese philosophy serves to highlight the differences between Chinese and Western Europeans with regard to beliefs about the nature of man, the ideal man, and general world view. These guide child rearing practices which in turn encourage specific personality traits and values. This paper deals with some implications that these differences have for psychoanalytic theory. PMID- 1289942 TI - Hilda Doolittle and creativity. Freud's gift. AB - The problem of work inhibition in a woman is addressed in terms of a specific case. The paper investigates the patient's view of how such an inhibition was cured in a brief analytic treatment of the American poet Hilda Doolittle conducted by Freud in 1933-34. PMID- 1289943 TI - Dreams. A developmental and longitudinal perspective. AB - In young children's dreams the infantile wish appears almost undisguised. Freud used this prototypical expression and representation of the infantile wish in a child's dream to bolster his conviction that the infantile wish was at the genetic root of adults' dreams as well. As development proceeds, a child's dream grows in disguise and complexity. This study of one analysand's dreams at age 5, 13, and 20 addresses the complexity from a longitudinal point of view and attempts to track the infantile wish through all of its developmental vicissitudes and disguises. PMID- 1289944 TI - On feeling and being felt with. AB - The development of feelings in early childhood is traced, with special emphasis on the mother's role during the toddler phase when she facilitates her child's transition from sensorimotoric discharge to the mental experience, ownership, and use of modulated affects. Many child analytic patients use defenses to ward off feelings, many have not even reached the developmental level of experiencing feelings. How this difficulty manifests itself, the reasons for the developmental lag, and the analytic means of helping such patients are discussed and illustrated. PMID- 1289945 TI - Latency development in children of primary nurturing fathers. Eight-year follow up. AB - This paper is an 8-year follow-up of 17 families in which fathers began as primary caretakers early in the lives of their children. The emphasis is on the developmental consequences for the children, now in the latency period, as well as their psychological experience of the father's increased significance. PMID- 1289946 TI - Extending the use of rubber dam isolation: alternative procedures. Part I. AB - Most dentists are well aware of the value of the rubber dam in allowing technical excellence; however, few recognize the potential for protecting the dentist and staff against the ever-growing number of carriers of the hepatitis and human immunodeficiency viruses. The effectiveness of the rubber dam as an isolation barrier is dependent on the consistency of its application. Sporadic rubber dam application is therefore a weak link in an infection control program. This paper describes additional modified utilizations of rubber dam, uses that are generally not attempted with restrictive orthodox application methods. In addition, practical hints on other means of retention are offered, with the emphasis on nuisance-free and easy application. PMID- 1289947 TI - Restorative decision-making behavior with magnification. AB - Assessment of occlusal fissure systems and restorations of amalgam in 100 extracted teeth were carried out by four examiners. An initial assessment, made with the naked eye, was repeated with binocular magnification (x 3). The data indicated that restorative decision-making behavior was modified when magnification was used, with an increase in the number of restorations planned for replacement and an increase in the number of tooth surfaces planned for restoration. Statistical analysis indicated that one of the examiners was particularly sensitive to the use of magnification and modified his treatment planning behavior considerably. As part of the process of adapting to the use of magnification, clinicians should review their decision-making behavior. PMID- 1289948 TI - Bleaching the natural dentition to match the color of existing restorations: case reports. AB - Vital tooth bleaching has become a popular and successful treatment. This treatment may be performed under controlled conditions in the dental office or it may be used under monitored, prescribed conditions with a 10% or 15% carbamide peroxide solution, applied by the patient at home. This paper presents the use of both types of systems in a unique application to modify the color of the natural dentition to match that of existing restorations. PMID- 1289949 TI - Visible light-hardened glass-ionomer-resin cement restorations for primary teeth: new developments. AB - Bonded glass-ionomer-silver-cement cement and visible light-hardened glass ionomer liner and base material have proven to be reliable dentinal and enamel restoratives since the mid-1980s. When used within their limitations, they offer advantages over mechanically interlocked silver amalgam material. A light hardened glass-ionomer-resin cement restorative material, which appears to have greater wear resistance and fracture toughness than prior glass-ionomer cements, has been introduced. This paper describes use of the new material and discusses its potential future implications. PMID- 1289950 TI - Dentigerous cyst associated with trauma to a primary incisor: a case report. AB - Trauma to primary incisors is common and poses a challenge to dentists who treat children. Often, the clinical appearance of such teeth does not indicate the underlying pathosis. In this case, a dentigerous cyst developed in association with an injured primary incisor, resulting in loss of a permanent tooth. PMID- 1289951 TI - Incisor spacing: a sequential orthodontic restorative treatment approach. AB - For those patients presenting with one or more missing incisors, a sequential technique utilizing specific arch wires to level and align the irregular incisor teeth may be used. Auxiliary coil springs are then fitted to redistribute the space prior to the preparation of a prosthesis, the fabrication of which is facilitated by parallel and upright abutments. The space obtained allows esthetically proportioned pontics. Two cases that illustrate this technique are presented. PMID- 1289952 TI - A concept of restorative treatment during orthodontic therapy. AB - Orthodontic therapy with fixed appliances bears a high risk of plaque accumulation, resulting in demineralization and new carious lesions. Rather than treat incipient lesions in orthodontic patients, most general dental practitioners decide to await future developments. A new concept for comprehensive restorative and endodontic treatment is presented, and its orthodontic implications are discussed. PMID- 1289953 TI - A unique manual for self-assessment by dental practitioners. AB - The Self Assessment Manual and Standards is produced by the Faculty of General Dental Practitioners of the Royal College of Surgeons of England and the Department of Health as part of a clinical audit program. It is a self-help manual containing a set of clinical standards in 15 aspects of patient care. The standards are concerned with clinical outcomes, rather than techniques, and are intended to be educational, not regulatory. The book's contents and applications are described in detail, together with its political background and possible use in an international context. PMID- 1289954 TI - Clinical performance of posterior composite resin restorations. AB - Two formulations of posterior composite resin (P-30 and Bisfil-P) were evaluated and compared to a high-copper, dispersed-phase amalgam (Dispersalloy). One hundred twenty-eight restorations were placed in 27 patients so that each patient received at least one of each material. After 3 years of clinical service, all three restorative materials produced clinically acceptable restorations, according to US Public Health Service and Leinfelder criteria. The amalgam restorations, however, underwent less wear (44 microns) than did the posterior composite resin restorations (60 to 74 microns). Stratification of data by type of tooth, class of restoration, and size of restoration produced the same ranking of wear from lowest to highest: Dispersalloy, Bisfil-P, and P-30. Resin restorations showed 45% more wear in molars than in premolars, and more wear was associated with moderately sized restorations than with conservative restorations. The surface texture of restorations of composite resin with porous strontium glass filler was nearly as smooth as that of enamel and was significantly smoother than that of the restorations of composite resin with zinc glass filler or of unpolished amalgam. PMID- 1289955 TI - Postextraction hemostasis in patients on anticoagulant therapy: the use of a fibrin sealant. AB - A simple and safe method of achieving hemostasis after tooth extraction in patients on anticoagulant therapy is described. The use of a tissue sealant turns a complicated, difficult, and risky dental procedure into a simple one, suitable for any dental clinic. Sixty-one teeth were extracted in 23 sessions. Only four cases of very slight postsurgical bleeding were reported. Dental treatment of the majority of these medically compromised people can be performed by private practitioners, without referring the patients to specialty care centers. PMID- 1289956 TI - The use of hypnosis with eating disorders. AB - This paper reviews the literature on the use of hypnosis in the assessment and treatment of eating disorders. It proposes that patients with eating disorders ought to be investigated as to the underlying dynamics behind the eating disorders symptoms. Following a thorough assessment, a number of hypnotherapeutic techniques are explained and discussed, such as: general relaxation and calmness, guided imagery, teaching self-hypnosis, ego-strengthening, direct and indirect suggestions for healing and recovery, cognitive restructuring and reframing, symbolic guided imagery, age progression ("back from the future" technique), metaphorical prescriptions, age regression and abreactions, and ego state therapy. Verbatim examples of these techniques are given as illustrations of how to use them. PMID- 1289957 TI - Untoward effects associated with hypnosis. AB - There are numerous reports of untoward effects associated with hypnosis but no reports of hypnosis per se causing a serious untoward effect. The context and manipulations performed are markedly different in the various settings where hypnosis is used. The various settings such as stage hypnosis, amateur hypnosis, clinical hypnosis, and research hypnosis must be considered separately when discussing untoward effects. Although the incidence of untoward effects has been studied in the research setting, the incidence of untoward effects is difficult to assess in some settings (such as stage and amateur hypnosis) and has not been adequately assessed in the clinical setting. After reviewing the literature on untoward effects in these various settings, I conclude that amateur and stage hypnosis should not be done because the risk is not balanced by possible benefits. Research hypnosis and clinical hypnosis by well-trained practitioners are safe procedures if certain guidelines are followed. PMID- 1289958 TI - Uses of hypnosis in treating anxiety states. AB - Hypnosis has come to be recognized as a potent antianxiety intervention which can be incorporated into a wide variety of psychotherapeutic models. It can play an important role in facilitating treatment of anxiety states, whether the treating clinician's orientation is biological, dynamic, interpersonal, cognitive or behavioral. The primary focus of this article is one the use of hypnosis in treating generalized anxiety disorder. An emphasis is placed on a behavioral or learning perspective. A specific treatment approach using this orientation is outlined and a case example is presented. PMID- 1289959 TI - The use of hypnosis in the treatment of PTSD. PMID- 1289960 TI - The use of hypnosis with dissociative disorders. AB - The dissociative disorders are characterized by difficulties in the integration of memory and/or identity. Typically this is manifested by amnesia and either the development of alternate identities or an estrangement from one's own identity. Spontaneous and self-generated dissociative states and phenomena sharing much in common with those that can be induced with hypnosis are thought to play a major role in their development, symptomatology, and perpetuation. Medical heterohypnosis offers a powerful tool to reestablish a functional continuity of memory and identity in many such cases. The application of hypnotic interventions in the treatment of such conditions will be discussed, explored, and illustrated with clinical vignettes. PMID- 1289961 TI - The use of hypnosis in sex and marital therapy. PMID- 1289962 TI - The use of hypnosis in obstetrics. PMID- 1289963 TI - The use of hypnosis in gynecology. PMID- 1289964 TI - The use of hypnosis in the treatment of burn patients. PMID- 1289965 TI - The use of hypnosis with hemophilia. AB - The Colorado program to treat hemophiliacs using hypnosis has been described. Those using hypnosis have realized a reduction in the need for transfusions, which results in a decrease in the development of inhibitors, less potential exposure to the AIDS virus and a lower incidence of liver and kidney damage. A decrease in the frequency and severity of bleeding episodes results in less morbidity and better coping in the face of HIV infection. Self-hypnosis has provided many bleeders with increased feelings of control and confidence and improved the quality of their lives. The field of psychoneuroimmunology gives a scientific rationale for what we have clinically recognized and implemented for years: self-hypnosis to alleviate stress has the potential to improve immune functioning. In bleeders and others who are HIV positive, it may augment medical attempts to impede the onset of AIDS. PMID- 1289966 TI - The use of hypnosis for temporomandibular joint (TMJ). PMID- 1289967 TI - Digital radiography in chest imaging. PMID- 1289968 TI - Digital gastrointestinal radiography. PMID- 1289969 TI - Digital musculoskeletal radiography. PMID- 1289970 TI - Digital genitourinary radiography. PMID- 1289972 TI - Digital radiography in mammography. PMID- 1289971 TI - Digital radiography in neuroradiology. PMID- 1289973 TI - Image management in radiology. PMID- 1289974 TI - Neural networks in diagnostic imaging. PMID- 1289975 TI - Presence and release of immunoreactive atrial natriuretic peptide in granulosa cells of the pig ovarian follicle. AB - Atrial natriuretic peptide (ANP) has been reported to be locally synthesized in the ovary although its physiological roles are still unknown. To define the origin of ovarian ANP, we demonstrated the presence and release of immunoreactive (ir) ANP in pig granulosa cells and characterized its biochemical properties. Serial dilution curves made with the extracts of pig granulosa cells, their perfusates and follicular fluid were paralleled to the standard curve of ANP. The amount of irANP in the granulosa cell was 2 fg/cell. The total amount of irANP in granulosa cells significantly correlated with the levels of irANP in follicular fluid. Additionally, the total content of irANP in the follicle negatively correlated with the follicular size. On reverse phase HPLC, the major form of irANP in granulosa cells and follicular fluid was high molecular weight but that in perfusate was low molecular weight. In Northern blot analysis, ANP mRNA was detected in the pig granulosa cells. Immunohistochemistry showed ANP prohormone location in granulosa cells of rat ovary. These data strongly suggest that the granulosa cells synthesize and secrete ANP. PMID- 1289976 TI - Vasodilator action of guinea pig vasoactive intestinal polypeptide (VIP): comparison with common mammalian VIP. AB - The vascular activity of guinea pig (gp) and common mammalian (p) VIP were compared in anesthetized guinea pigs and dogs. In the guinea pig, intravenous injections of gpVIP and pVIP increased pancreatic blood flow and reduced the systemic arterial pressure and pancreatic vascular resistance in a dose-related manner. There were no significant differences in the vasodilator actions of these two VIPs, indicating that the overall cardiovascular actions of gpVIP and pVIP are similar in guinea pigs. In the dog, gpVIP, when given intra-arterially, was less potent (about 1/4) than pVIP in its action on femoral blood flow, suggesting that the blood vessels of the dog hind leg are more sensitive to its own VIP than to gpVIP. Oxidation of pVIP and gpVIP with H2O2 greatly reduced their vasodilator effects on the femoral arterial blood flow. The vascular effects were restored to control levels by reduction of the oxidized peptides with mercaptoethanol, which suggests that methionine residues of gpVIP and pVIP are important in the vasodilator effect on the femoral arterial bed in dogs. PMID- 1289977 TI - [Is there still any place for non-Anglosaxon literature in orthopedics?]. PMID- 1289978 TI - [Arthroscopic meniscectomy. Comparison of the functional results of meniscectomy in patients above and under 45 years of age. Apropos of 107 cases]. AB - A comparative retrospective study of 107 cases of arthroscopic meniscectomies performed between December 1985 and December 1988 on 52 operated patients under 45 (P1 = 54 knees) and 52 operated patients over 45 (P2 = 53 knees). Those two populations have been selected among 292 isolated meniscal lesions files (without anterior cruciate ligament tear) operated for arthroscopic meniscectomy between 1985 and 1988. There were 81 medial meniscus lesions, 16 lateral meniscus lesions and 10 bi-meniscal lesions. The follow-up was for 1 to 5 years with a score of 70.3 per cent functional satisfactory results for the above 45 years (P2) and a score of 89.4 per cent below 45 (P1). Regarding the medial meniscus lesions only, we count 76 per cent (P2) satisfactory results versus 87.5 per cent (P1). This assessment can be easily explained by the variety of meniscal lesions (8 degenerative meniscal lesions among P2 namely 15 per cent), by associated cartilage lesions of the medial compartment of the knee (medial condyle: P2 = 37.75 per cent, medial tibial plateau: P2 = 41.5 per cent) and by genu varum deformity. However, in spite of this significant statistical difference (alpha < 0.05), we don't think we should condemn the arthroscopic meniscectomy over 45: the morbidity is very low and if some patients were not cured, the majority of them said that they improved after the operation. The cartilaginous degenerations of the medial compartment, discovered during arthroscopy, in a context of genu varum, don't need any tibial osteotomy at first, especially if they are asymptomatic and without tibia varum. PMID- 1289980 TI - [Recurvatum in arthritic genu valgum. Contraindication for osteotomy and unicompartmental prosthesis]. AB - Nine lateral gonarthroses were accompanied by a preoperative recurvatum. The recurvatum of arthritic origin is rare. It appears only at a late stage of the arthritis evolution in the genu valgum. Considering the series results, it constitutes a contraindication to the treatment by osteotomy or by unicompartmental prosthesis. PMID- 1289979 TI - [Meniscal injury in the plastic reconstruction of the anterior cruciate ligament. Meniscal suture or abstention]. AB - The purpose of this study was to observe the change of the meniscal lesions, which are conservable by suture or simply by leaving-in-place within the frame of operated anterior instability. Forty-six knees which had been operated by the free transplant of bone-patellar tendon-bone, presented the associated lesions of conservable meniscus. These lesions were treated by suture of the meniscus in 15 cases and left in place in 31 cases. The programme of rehabilitation was the same in the two groups. All the patients have been followed-up for 26 months in average (12-40 months). In the group of meniscal suture, only one secondary meniscectomy was carried out. 8 patients presented moderate pain on the corresponding femorotibial joint line and 5/13 of the sportive patients recovered to the same level of activity. In the group of leaving-in-place, no meniscectomy has been carried out. Only 4 patients complained of pain and 23/27 recovered to the same activity level. The arthrographic and arthroscopic observations have been carried out in 23 cases. They confirmed the cicatrization of the sutured meniscus but also showed the possibility of total or partial cicatrization of the lesions left in place (12 on 13). The authors conclude that the peripheral meniscal lesions associated with the operation of the chronic anterior instability do not always require suture. The abstention on the meniscal lesion is possible if it is limited on the posterior segment: Then the functional results seem better. PMID- 1289981 TI - [Instability and misdiagnosed or neglected dislocations of the upper cervical spine in children. Apropos of 20 cases]. AB - Neglected instabilities or luxations of the upper cervical spine in children are rare if one discards conditions such as chondrodysplasia, Down Syndrome or others, were the spine is known to be at high risk of instability. We have studied twenty cases of neglected luxations and the delay in diagnosis is explained either by the asymptomatic character of some of these lesions, or by the difficulty in diagnosis. At the occipito-atlantal level we have reviewed: an instability in translation which required an occipito-axial fusion; two compensatory counter occipito-atlantal luxation of an atlanto-axial rotatory fixation. The diagnosis was best made with computed tomography scan and the treatment was not much different from the isolated atlanto-axial rotatory luxation. An instability in flexion extension, which was merely followed at regular intervals. At the atlanto-axial level 9 cases of sagittal instabilities in kyphosis and translation with a distance between atlas and axis of more than 5 mm were observed. These instabilities were most often associated with a malformation of the cranio-cervical junction; their treatment was usually surgical by means of an atlanto-axial or occipito-axial arthrodesis depending on the case. 9 other cases of atlanto-axial rotatory luxations were either isolated (7 cases) or associated with a counter occipito-atlantal rotatory subluxation (2 cases). Their diagnosis was made on routine X-rays, but the complete or incomplete aspect of the luxation, as well as its fixed aspect, was best appreciated with dynamic CT scan. Their treatment was always started with collar neck or halo traction in order to obtain, reduction of the dislocation, or at least the disparition of the torticollis and the head straight up on shoulders. The stability of the spine was achieved with a minerva cast jacket, halo cast or spine fusion depending on the case. PMID- 1289982 TI - [Surgical treatment of scoliosis in bed-ridden patients with cerebral palsy]. AB - Thirty-two scoliosis in total body involved children with cerebral palsy (CP) were reviewed. Mean preoperative angle was 13. Average follow-up was four years. Surgery included a single posterior (11 cases) or anterior (3 cases) approach and a double stage anterior and posterior procedure in 18 cases. Fusion was extended to the sacrum in 15 cases. Complications were numerous: 3 deaths, 15 postoperative complications in 10 patients. Most of them were septic and cutaneous. Cobb angle was 78 degrees before surgery, 28 degrees after surgery and 32 degrees at follow-up. Functional status was improved in most of cases. Pain disappeared in 2/3 of cases. Sitting position was acquired in all cases at follow up; motor possibilities were improved in 1/4 of cases; associated medical pathologies (mainly respiratory) were reduced in 2/3 of cases. PMID- 1289983 TI - [Treatment of metastases of thoracic and lumbar vertebrae with predominant corporeal involvement by osteotomy of the vertebral body and anterior approach with cement and screwed plate]. AB - Forty-seven patients with predominant corporeal thoracic, thoraco-lumbar or lumbar vertebral metastases were treated surgically by corporectomy. The vertebral body was replaced by acrylic cement sustained by a vertebral U shaped plate screwed to the adjacent vertebral bodies: this corporectomy was completed in 17 cases by a posterior approach. In 9 cases it allowed to treat a posterior epiduritis. The spinal metastases were symptomatic in 45 cases (pain and/or neurologic deficit); 22 of the operated patients were bed-ridden, either due to an important pain (16), or due to a severe neurological deficit (6). In 36 cases, the intervention was done on the spinal lord segment (7 times on the upper thoracic column). The patients were authorized to get up the fifth or sixth postoperative day. The functional results, at a price of 15 per cent of mortality during the first two postoperative months, were satisfactory and stable in time (particularly, 70 per cent of the operated patients with neurologic deficits were improved and 13 of the 21 bed-ridden became autonomous). The intracanalar decompressions controlled by a postoperative myelography, were nearly always total. The sets were stables in time when the block of cement was sustained by a metallic device. The mortality and the functional failure with pain and neurological impairment occurred essentially, when there was spreading of the tumor to the peri-vertebral soft tissues and when there was epiduritis extending beyond the bone lesion. Thus, to be perfectly efficacious, the anterior surgery of the vertebral metastasis, which gives durable and better results than the posterior one, should be soon enough integrated, in the global treatment of the metastatic disease. PMID- 1289984 TI - [Supracondylar fractures of the humerus associated with ipsilateral fractures of the forearm]. AB - We report 20 cases of ipsilateral supracondylar elbow fracture and forearm fracture in childhood. The mean follow-up was 20 months. For an analysis of the results, we used a global rotation of the upper limb. We appreciated the motion and the carrying angle of the elbow and the wrist. 15 cases were very good or good; there were 4 cubitus varus without functional impairment and 1 failure after one open Monteggia fracture. The therapeutic strategy is discussed. If one does not want to increase the damage to periosteum in the elbow during the forearm reduction, one must first reduce the supracondylar fracture and fix it by 2 pins like in Judet procedure. Then, the forearm fracture should be treated conservatively. PMID- 1289985 TI - [Screwed acetabulum: results of 72 cases with a mean follow-up of 5 years]. AB - Ninety-seven threaded acetabular prostheses (44 cups of Lord and 53 Motta, type cups) were implanted among which 72 were examined at an average follow-up of 5.9 years. After an initial phase of good tolerance, the results became rapidly degraded. Clinically, the lack of fixation was translated by a start up pain. On examination, the pain provoked by the opposed hip flexion was pathognomonic. A radiographic analysis of our checks allowed us to classify them in four types: Type I: painful hip, normal radiography or presence of a radiolucent line in one of the DeLee's zones; increased uptake at bone scanning. Type II: total radiolucent demarcation; Type III: axial migration; Type IV: migration and tilting; Finally analysis of our series with Kaplan-Meier method showed a survivorship rate at five years of 59.3 per cent. It is concluded that this kind of implant must be abandoned. PMID- 1289986 TI - [Replacement of the proximal part of the femur in total hip prosthesis. Clinical and experimental research]. PMID- 1289987 TI - A V(D)J site-specific recombination model involving no compulsory double-stranded break formation at the coding segments. AB - Complete immunoglobulin and T-cell-receptor genes are assembled by site-specific recombination of separately encoded gene segments. We present a novel recombination model which accounts for all the characteristics of V(D)J recombination that have been described. The sequence of events proposed implies no formation of double-stranded breaks at the coding ends, ensuring continuity between the recombination partners during the reaction, and solves the problem of the ligation of extremities which have no complementarity. According to this recombination model, the formation of covalently sealed coding ends does not constitute a compulsory step in the recombination process. PMID- 1289988 TI - Human monoclonal IgM antibodies from foetal B-cell hybridomas directed against a surface antigen on human tumour cells. AB - In order to assess the existence of B lymphocytes capable of producing anti tumour antibodies in non-tumour-bearing individuals, human lymphocytes derived from foetuses and adults were fused with the heteromyeloma cell line CB-F7. By indirect immunofluorescence, 29 out of 4,472 IgM-producing hybridomas (from 8 foetuses and 8 adults) were shown to produce antibodies which bind to colon carcinoma lines Colo205 and SW620, Raji lymphoma cells and small cell carcinoma of the lung. In vitro growth of tumour cells recognized by these antibodies was inhibited. The antibodies also mediated complement-dependent cytotoxicity. All antibodies tested recognized a cell surface molecule of 55 kDa. Southern blot hybridization analysis of hybridoma DNA with a human JH probe showed that the hybridomas were derived from clonally unrelated B cells. These results demonstrate that human foetal and adult B cells from non-tumour-bearing individuals are able to produce IgM antibodies recognizing defined cell surface molecules expressed on some tumour cells. PMID- 1289989 TI - Ultrastructural changes in mouse peritoneal mast cells in response to L-leucine methyl ester or anti-IgE. AB - We studied the ultrastructural features of mouse peritoneal mast cells in response to a non-immunologic lysosomotropic agent, L-leucine methyl ester (Leu OMe), as compared to well-known immunologic stimulation mediated by anti-IgE antibodies. Total peritoneal exudate cells were collected from CBA/J mice, with mast cells representing 3 to 8% of total cells. The secretory granules in unstimulated mast cells were heterogeneous in size and shape, but intragranular material displayed a homogeneous electron-dense appearance. Stimulation with either Leu-OMe, for Leu-OMe doses lower than 1.5 mM, or anti-IgE was associated with fusion of the granule membranes with one another and with the plasma membrane, as evidenced by morphologic changes noted by electron microscopy. Ultrastructurally, electron density characterizing the granular matrix decreased to varying degrees in the granules, as did its homogeneity, even within a given mast cell. At higher Leu-OMe doses (> 1.5 mM), the effect of this lysosomotropic compound on mast cells was associated with an apparent loss of membrane and cellular integrity, suggesting high Leu-OMe dose-mediated cytotoxicity. These results show that activation induced in mouse peritoneal mast cells by Leu-OMe and anti-IgE may have distinct characteristics, as assessed by morphologically different patterns. Furthermore, high Leu-OMe doses (> 1.5 mM) induced cytotoxicity targeted toward mast cells. PMID- 1289990 TI - Detection of autologous antiidiotypic antibody-forming cells by a modified enzyme linked immunospot (ELISPOT). AB - We describe here the utilization of a modified enzyme-linked immunospot assay (ELISPOT) in order to detect an autologous antiidiotypic response in mice at the level of single antibody-forming cells (AFC). Severals assays have been routinely used to detect anti-Id producing cells; however, these approaches often produce contrasting data. We present results obtained with the modified ELISPOT, using as a model system the antiidiotypic response in mice after immunization with a vaccine from Streptococcus pneumoniae R36a, expressing the immunodominant epitope phosphorylcholine (PC). The response to PC is mediated by a large fraction of antibodies bearing the public idiotype T15. Mice of different genetics make up were immunized with a single injection of the vaccine. We observed that one mouse strain (D1.LP) out of three was able to mount a significant anti-T15 response during the primary anti-phosphorylcholine response. BALB/c and C57BL/6 mice did not produce significant levels of anti-T15 antibody following a single injection of the antigen. In contrast, BALB/c mice which were repeatedly stimulated showed a specific anti-Id response. Experimental controls were performed using either specific anti-T15 monoclonal antibodies (mAb) or splenocytes from mice immunized with TEPC15 myeloma protein in complete Freund's adjuvant. PMID- 1289991 TI - Nacre of abalone shell: a natural multifunctional nanolaminated ceramic-polymer composite material. PMID- 1289992 TI - Molecular architecture of helicoidal proteinaceous eggshells. AB - I will not attempt to summarize this chapter, which is already a summary. I merely wish to point out that experimental and theoretical evidence to date clearly suggests that antiparallel beta-pleated sheet dictates self-assembly in helicoidal proteinaceous eggshells. Molecular details of this process have started to become clear after the development of the specific, most probably correct, protein structural models in the case of the silkmoths, where amino acid information is available and with the help of several experimental techniques. However, for people seeking universal mechanisms the picture should still be far from complete. Several analogous systems should be studied before providing final answers. PMID- 1289993 TI - Secretory proteins of Chironomus salivary glands: structural motifs and assembly characteristics of a novel biopolymer. AB - Salivary glands of Chironomus synthesize a family of at least ten secretory proteins that can be grouped into three size classes: the large (about 1000 kDa), intermediate (100- to 200 kDa), and small (less than 100 kDa). After synthesis, secretory proteins undergo a dramatic transformation to form a novel biopolymer. Secretory proteins accumulate in the central lumen of the gland, forming dissociable complexes that appear as a network of smooth fibrils and multistranded beaded fibers. When secretory protein complexes are extruded through the secretory duct, the fibers become oriented in parallel arrays; when these parallel arrays of fibers emerge from the mouth of larvae they are an insoluble, silk-like thread. Regulation of secretory protein-coding gene expression determines which secretory proteins are synthesized, thus, the composition of silk threads. At least two types of threads are produced: larval silk is used to construct tubes for protective housing and assist with feeding; prepupal silk is used to construct tubes for larval/pupal ecdysis (pupation). Variations in composition presumably contribute to different mechanical properties of larval and prepupal silk threads. Since the macroscopic physical properties of polymerized silk most likely reflect the microscopic structure and interaction of secretory proteins, it becomes important to learn the principles which govern secretory protein assembly at the molecular level. Which secretory proteins interact and what are the sites used for intraportein and protein protein interactions during the assembly of this biopolymer? All eight secretory proteins characterized thus far contain tandemly repeated peptide sequences (ranging from 14-90 amino acids in length) and/or a periodic distribution of Cys residues. These motifs appear to be unique; no other biopolymer has either the repeated peptide sequences or composite structure of chironomid silk threads. The evolutionary conservation of motifs within repeats and among different secretory proteins suggests that the sequences and three-dimensional structures of the motifs may be important for assembly of secretory proteins into complexes, oriented fibers, and silk threads. Further study of secretory protein assembly will bring us closer to understanding how this silk assembles in vivo. By learning principles that nature employs to construct such a novel composite biopolymer, it may become feasible to design and produce new classes of fibers or biomolecular materials with distinctive properties that are currently unavailable. PMID- 1289994 TI - Spider silk: a mystery starting to unravel. PMID- 1289995 TI - The nature and role of liquid crystalline order in silk secretions. PMID- 1289996 TI - The formation of mussel byssus: anatomy of a natural manufacturing process. PMID- 1289997 TI - Micromechanics of natural composites. PMID- 1289998 TI - Reflections on the structure of mussel adhesive proteins. PMID- 1289999 TI - Composition and design of Fasciola hepatica eggshells. PMID- 1290000 TI - The cell and molecular biology of eggshell formation in Schistosoma mansoni. PMID- 1290001 TI - [Home management of a child with a cancerous pathology]. PMID- 1290002 TI - [In a rehabilitation center, daily life for a child with spina bifida]. PMID- 1290003 TI - [Social aide for children: the nurses are there...]. PMID- 1290004 TI - [Revitalization of old people: is it a part of nursing care?]. PMID- 1290005 TI - [Nursing process in home care: we believe in it!]. PMID- 1290006 TI - [The computer, good or bad partner?]. PMID- 1290007 TI - [Ergonomics, sports, life hygiene ... good tools for work without injury or pain!]. PMID- 1290008 TI - [Hepatitis B: a indispensable vaccination for health personnel]. PMID- 1290009 TI - [AIDS: to be better defined...]. PMID- 1290010 TI - [The operating suite and recovery room: a world to discover ... with urgency!]. PMID- 1290011 TI - [What's new in the pharmacopoeias?]. PMID- 1290012 TI - ["Sophrology", a method to cure stress?]. PMID- 1290013 TI - [Adolescents, protect your health capital!]. PMID- 1290014 TI - [Should we and how can we modify the behavior of adolescent smokers?]. PMID- 1290015 TI - [Being a nurse and the president of departmental committee for health education]. PMID- 1290016 TI - [Is the nurse always in the service of the patient?]. PMID- 1290017 TI - Clinical and family studies in Hungarian patients with gout. AB - In this study we examined 22 Hungarian male probands with gout and 105 of their first degree relatives. This was the first family study in Hungary in which the characteristics of distribution of gout and hyperuricaemia among patients with gout and their first degree relatives, as well as the possible correlation between the prevalence of the disease and MHC class I antigens was investigated. Our gout patients showed the following characteristics: (1) There was a typical onset after age 40, benign oligoarticular form of arthritis, underexcretion of uric acid, moderate hypertension without evidence of reduced renal function, and a relatively high frequency of hyperostosis. (2) The prevalence of hyperuricaemia and gout exceeded the general population level in the first degree relatives of our gout patients. (3) The distribution of MHC class I antigens among the first degree relatives of our patients with gout showed no characteristic patterns. (4) There was no correlation between HLA B27 antigens and prevalence of gout or hyperostosis in family sibling studies. (5) The high frequency of gout and hyperuricaemia, as well as the lack of characteristic HLA patterns among the first degree relatives of gout patients in our family studies, point to the possible cumulative effect of several genes and environmental factors in the etiopathogenesis of this disease. PMID- 1290018 TI - MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Results of a multicenter study. SLE Study Group. AB - Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies. PMID- 1290020 TI - The relative roles of C4A and C4B in prevention of immune precipitation, solubilisation and immune adherence. AB - C4A and C4B levels were measured in serum from 246 normal individuals. Complement mediated solubilisation, assayed using alkaline phosphatase anti-alkaline phosphatase immune complexes (IC), correlated with both C4A and C4B levels. However, C4A and C4B levels showed no correlation with solubilisation of bovine serum albumin (BSA) ICs, or with the prevention of immune precipitation of BSA or alkaline phosphatase ICs, nor with immune adherence assayed using thyroglobulin and BSA ICs. PMID- 1290019 TI - Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis. German Lymphokine Study Group. AB - The controlled clinical trial reported here is part of a multicenter clinical and basic research project, sponsored by the German Federal Minister of Science and Technology, directed by a standing commission of the president of the Max-Planck Gesellschaft, and coordinated by the Max-Planck-Institut fur Biochemie, Munchen. Overall, 249 patients with rheumatoid arthritis (RA) were enrolled by 16 participating hospitals. In addition to NSAID treatment, patients were randomly given either interferon gamma (IFN-gamma) or placebo. In the IFN-gamma group, 107 patients were evaluated and in the control group, 116 patients were evaluated. The response rate after 3 months of treatment, according to joint pain indexes, was significantly higher in the IFN-gamma group with an error probability of 1%. IFN-gamma was able to reduce the quantity of corticosteroids administered. Compared with the control group, the IFN-gamma group benefited considering all parameters measured. Most important side effects were transient fever and transient influenza-like symptoms; all other adverse events were comparable in both groups. PMID- 1290021 TI - Abnormal galactosylation of serum IgG in patients with systemic lupus erythematosus and members of families with high frequency of autoimmune diseases. AB - Gas chromatographic carbohydrate analyses of IgG from 30 patients with idiopathic systemic lupus erythematosus (SLE) revealed lower content of galactose when compared to that in 36 controls of similar ages (mean +/- SD, 3.18 +/- 0.66 vs 3.82 +/- 0.41 galactose residues/mole of IgG, P < 0.001). Abnormal galactosylation was observed in 60% of SLE patients. Analyses of IgG from 58 members of five families, characterized by a high frequency of SLE and other autoimmune diseases and serological abnormalities, and 51 controls of similar age range revealed that IgG galactose deficiency was detectable not only in some members with clinical and serological abnormalities (P < or = 0.001), but also in those without evidence of autoimmune diseases or abnormal serologies (P < or = 0.001). These data indicate that abnormal galactosylation of IgG frequently occurs in asymptomatic members of families with a high frequency of SLE and other autoimmune diseases and suggests that this abnormality may be an indicator for the development of these diseases. PMID- 1290022 TI - Transferrin microheterogeneity in rheumatoid arthritis. Relation with disease activity and anemia of chronic disease. AB - We studied the relation between disease activity in rheumatoid arthritis (RA) and the microheterogeneity of transferrin. Using crossed immuno isoelectric focusing, transferrin microheterogeneity patterns were analyzed in sera of healthy individuals, nonanemic RA patients, iron deficient RA patients and RA patients with the anemia of chronic disease (ACD). In all RA groups a significant shift in the microheterogeneity pattern was observed, reflecting increased synthesis of transferrins with highly branched glycan chains. Increased disease activity correlated with both the induction of ACD and the change in transferrin glycosylation, which was, therefore, most pronounced in ACD. Generally, an increased synthesis of glycoproteins is accompanied by alterations in their glycosylation pattern. Since transferrin is a negative acute phase protein, our results indicated that changes in synthetic rates and changes in glycosylation induced in the acute phase response are regulated independently. PMID- 1290023 TI - Osteocalcin in patients with rheumatoid arthritis--effect of anatomical stages, inflammatory activity and therapy. AB - The aim of this study was to investigate whether the degree of inflammatory activity, the anatomical stage and various treatments have an influence on bone turnover in patients with rheumatoid arthritis (RA). Osteocalcin (OC) and other parameters of bone turnover were measured in 131 patients with RA. The mean values of alkaline phosphatase (AP), but not of OC were significantly (P < 0.01) higher in our patients compared to controls. In contrast to AP, OC values increased and correlated significantly (r = +0.33, P < 0.01) with ascending anatomical stage in women not on glucocorticoid treatment. As regards therapy, we found significantly lower OC levels in women receiving steroids compared to controls (P < 0.03) and those being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.03), methotrexate (MTX) (P < 0.05), or gold (P < 0.01). Females treated with gold had higher OC levels than patients receiving no antirheumatic drugs (P < 0.03). Furthermore, there was a significantly negative correlation between OC and inflammatory activity [C-reactive protein (CRP)] (r = 0.25, P < 0.003). In conclusion, OC levels were significantly higher (P < 0.032) in patients with advanced (anatomical) stages of RA. In contrast to AP, changes in bone turnover, such as suppression of bone formation by steroids and high inflammatory activity in patients with RA, were easily detected. PMID- 1290025 TI - A prospective study of tumor markers CA 125 and CA 19.9 in patients with epithelial ovarian carcinomas. AB - In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovarian cancer [121 with active disease, 108 in complete remission (CR)], and in 20 patients with other malignancies. Abnormal levels of CA 125 were found in 90% of patients with active ovarian cancer, in 1.8% of those in CR and in 38% of cases with other malignancies. Abnormal CA 19.9 serum levels were found in 36, 9 and 48% of these groups, respectively. Serum levels of both tumor markers were related to tumor stage and histological type. The highest levels of CA 125 were found in serous adenocarcinoma and the lowest in the mucinous type (p < 0.0001). In contrast, significantly higher CA 19.9 values were found in mucinous carcinoma than in other histologies (p < 0.0001). CA 125 and CA 19.9 were useful for monitoring disease activity in 88.3 and 32%, respectively, while one or other tumor marker was useful in 92% of patients. At the time of the second-look operation, abnormal CA 125 serum levels were found in 32% (6/19) of patients with active disease and in none of those with CR (0/38). CA 125 sensitivity was 83% (5/6) in those patients with residual tumor > 2 cm and in 8% (1/13) in those with tumor < 2 cm. CA 19.9 values were abnormally high in 16% of cases with persistent disease and in 11% of CR patients. In conclusion, our results confirm that CA 125 is a useful marker in ovarian carcinoma. CA 19.9 improves the results obtained with CA 125 alone only in mucinous adenocarcinomas. PMID- 1290024 TI - Studies on carrageenan-induced arthritis in adult rats: presence of nerve growth factor and role of sympathetic innervation. AB - Recent studies effected by our Institute indicate that various forms of human arthritis express both immunohistochemically and biologically active nerve growth factor (NGF) in the synovium. In the present study, we used a model of carrageenan-induced arthritis to further evaluate the effects of joint inflammation on NGF level. These studies showed that experimentally-induced arthritis in rats caused a significant increase in NGF in the perivascular area of the synovium. We also showed that injection into the synovium of purified NGF did not cause inflammation per se and that the destruction of peripheral sympathetic innervation significantly reduced both the inflammation and the level of NGF following carrageenan injection. PMID- 1290026 TI - Combined evaluation of serum CA 125 and CAM 29 in patients with epithelial ovarian cancer. AB - We examined 92 patients with epithelial ovarian cancer and 262 patients with benign ovarian diseases undergoing laparotomy. On the basis of a nonparametric method, antigen levels corresponding to prefixed 95% specificity values in a group of 674 women with benign gynecologic diseases were taken as cutoff limits (88.8 U/ml for CA 125 and 13.7 U/ml for CAM 29). Moreover, CA 125 and CAM 29 levels were measured serially during and after chemotherapy in 26 women selected from the patients with advanced epithelial ovarian cancer. At diagnosis, serum CA 125 was as sensitive as serum CAM 29 for nonmucinous tumors, but more sensitive than serum CAM 29 for mucinous tumors. The association of the two markers seemed to give no advantage over the CA 125 assay alone in the diagnosis of epithelial ovarian cancer. In monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer, changes in CA 125 levels correlated with the clinical course of disease better than changes in CAM 29 levels, and the serum CA 125 assay was more reliable than the serum CAM 29 assay in the early detection of tumor progression. In conclusion, serum CAM 29 did not seem to represent a complementary assay to serum CA 125 in the management of patients with epithelial ovarian cancer. PMID- 1290027 TI - Immunohistochemical analysis of pancreatic secretory trypsin inhibitor expression in pulmonary adenocarcinoma: its possible participation in scar formation of the tumor tissues. AB - The expression of pancreatic secretory trypsin inhibitor (PSTI) was examined immunohistochemically in pulmonary adenocarcinoma. Of 86 carcinomas examined, 65 (76%) showed immunoreactivity for PSTI. Cases with the papillary subtype and those with early stage disease contained PSTI in cancer cells more frequently and were more strongly positive. There was a slight tendency to strong expression of PSTI in cases with the histologically well-differentiated type, tumor size of approximately 30 mm maximum diameter, and marked scar formation. Furthermore, 37 cases, which were the majority of the PSTI-positives, appeared to contain PSTI predominantly in cancer cells within the central or subpleural scar tissue and/or its surrounding tissue. Thus, pulmonary adenocarcinoma may commonly express PSTI and, considering previous reports that PSTI acts as a growth factor-like substance on fibroblasts in vitro in addition to the present findings of its immunohistochemical distribution in the tumor tissues, it is suggested that PSTI expressed in cancer cells of some pulmonary adenocarcinomas may possibly participate in tumor scar formation. PMID- 1290028 TI - Differences in messenger RNA expression of carcinoembryonic antigen in surgical specimens of colorectal carcinoma. AB - Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. Plasma CEA levels have been variably associated with prognosis. Since plasma CEA level is multifactorial, CEA gene expression in tumors may provide one precise mechanism to evaluate its functional role. This study evaluated CEA expression at the messenger RNA (mRNA) level in 22 human colorectal carcinomas and their adjacent normal mucosae by Northern blot hybridization using a 32P-labeled CEA probe (a loop-domain specific cDNA, LV7). Both tumor and normal mucosa displayed three mRNA species of 4.0, 3.6, and 3.0 kb in length. The expression of 3.6-kb mRNA which encodes for CEA was dominant and it was correlated with another 4.0-kb CEA mRNA expression. The expression of 3.0 kb mRNA which encodes for nonspecific cross-reacting antigen was weak and not detectable in 8 of 22 colon tumors and 12 of 22 normal colon mucosae. In only one tumor, a 4.5-kb mRNA (which might encode for a new family member of CEA) was expressed. A two- to fourfold higher expression of CEA mRNA (3.6 kb) was observed in 11 of 22 colorectal tumors (2 of 9 proximal colon tumors and 9 of 14 rectosigmoid tumors) when compared with morphologically normal adjacent mucosae. Preoperative plasma CEA levels and Dukes' staging had no correlation with this CEA mRNA expression. CEA mRNA did not appear to correlate with metastasis because its expression in the primary colon cancers with metastases (Dukes' stage D tumor) was not always increased. These data also imply that factors other than mRNA expression in tumor might be important in regulating plasma CEA levels. PMID- 1290029 TI - Expression of mRNA of SCC antigen in squamous cells. AB - The expression of SCC antigen mRNA was studied by Northern blot analysis and in situ hybridization in human gynecologic tissues. Northern blot analysis revealed that mRNA of SCC antigen was expressed strongly in normal squamous epithelium and columnar epithelium of the uterine cervix, but not in the endometrium, fallopian tube or ovarian tissue. Among gynecologic malignancies, squamous cell carcinoma of the uterine cervix expressed mRNA of SCC antigen, whereas endometrial and ovarian adenocarcinoma were negative. With in situ hybridization, mRNA of SCC antigen is located in the basal and parabasal layers of the normal squamous epithelium, in dysplasia, and also in carcinoma in situ and invasive squamous cell carcinoma. These results confirmed the previous findings by immunohistochemical studies that SCC antigen is closely related to squamous cells, but also raised a new puzzle regarding the different localization of mRNA and its product, SCC antigen, in the normal squamous epithelium. PMID- 1290030 TI - Ontogeny of pancreatic oncofetal antigen. AB - Serum concentration of pancreatic oncofetal antigen (POA) was determined in human fetuses, newborns and pregnant women. The mean fetal concentration of POA (mean = 5.27 micrograms/ml) changed very little with gestational age. Also, only a weak correlation was found between POA concentration of newborns (mean = 5.15 micrograms/ml) and their birth weight. It appears that between the 19th and 40th weeks of gestation POA exhibits no fetospecific features, i.e. POA concentration did not exceed significantly the concentration of nonpregnant adults (mean = 6.10 micrograms/ml). A number of pathophysiological variables was correlated with POA concentrations of newborns. The most striking statistical differences were found between American black and white newborns and adults; the mean concentration of POA in sera of black full-term newborns was 5.38 micrograms/ml as compared to white newborns, where the mean concentration was 3.58 micrograms/ml. Similarly, black mothers had a mean concentration (mean = 12.21 micrograms/ml) significantly greater than white mothers (mean = 5.62 micrograms/ml). PMID- 1290031 TI - Serum neuron-specific enolase in diagnosis and follow-up of gastrointestinal neuroendocrine tumors. AB - Neuron-specific enolase (NSE), the glycolytic isoenzyme of the enolase gamma gamma dimer, is a specific marker for the diffuse neuroendocrine system and derivative tumors (NET). Serum levels of NSE were measured in 39 patients with NET of the gastrointestinal tract (including 3 gastric and 13 intestinal carcinoid tumors, 6 gastrinomas, 3 insulinomas, 1 glucagonoma, 2 mixed islet cell tumors, 11 neuroendocrine pancreatic carcinomas), in 15 healthy subjects and in 15 nonendocrine gastric, pancreatic, and intestinal tumors. Thirty-six of the 39 patients had elevated circulating levels of NSE, 2 insulinomas and 1 gastrinoma had values below 12 ng/ml like healthy subjects and nonendocrine tumors. No significant difference of serum NSE was found between 23 'functioning' and 16 'nonfunctioning' NET. Fourteen of the NET were malignant, and NSE circulating values were significantly higher than those of nonmalignant forms. After curative surgery serum NSE decreased significantly. NSE can be considered a reliable marker in the differential diagnosis between endocrine and nonendocrine neoplasms, in the clinical detection of silent endocrine tumors and in the follow up of NET. PMID- 1290032 TI - Comparison of mitogen- and virus-induced interferon production in whole blood cell cultures of patients with various solid carcinomas and controls. AB - Using a sensitive immunoassay, the mitogen-induced production of interferon-gamma (IFN-gamma) and virus-stimulated IFN-alpha production was investigated in whole blood cell cultures of 115 control subjects and 225 untreated patients with various solid carcinomas. In the cultures of the tumor patients, significantly lower levels of IFN-gamma were found as compared to the controls (p < or = 0.001) and the differences were most evident in those tumor groups containing mostly patients with advanced clinical stages. IFN-alpha values were only slightly lower in the cultures of the carcinoma patients, with p values < or = 0.05. Statistically, there was no correlation between IFN-alpha and IFN-gamma values. Since the IFN-gamma differences between tumor and controls and the correlation to groups with higher tumor stages were much clearer than IFN-alpha differences, we conclude that IFN-gamma measurements after polyclonal induction may be the better parameter for showing a depressed cellular immunological activity in patients with malignancies than virus-induced IFN-alpha secretion. PMID- 1290033 TI - Divergence in patterns of invasion among subpopulations derived from a human carcinoma clone: roles of intercellular contacts and of cell-substratum adhesion. AB - In tumor progression, populations of cancer cells with different patterns of growth and invasion arise within the same tissue and within individual neoplasms. We tested the hypothesis that, even in histologically undifferentiated carcinomas, such diversity may be influenced by differentiation-dependent adhesive mechanisms. We used as prototypes two cell lines that originated in the same clone of a poorly differentiated cervical carcinoma, but express strikingly different phenotypes. Cells of line C-4I express select characteristics of the spinous stage of stratified squamous epithelial differentiation while cells of line C-4II resemble basal cells. C-4I cells form rapidly expanding compact tumors in vivo and multilayered cohesive colonies in culture, while C-4II cells form slow-growing infiltrating tumors in vivo and dispersed, monolayered colonies in culture. In suspension culture which prevented any cell-substratum interactions, C-4I cells formed aggregates that were significantly larger and more compact than those formed by C-4II. Thus, greater intercellular adhesion between the 'spinous' C-4I cells contributed significantly to the phenotypic divergence of the lines. Upon disruption of intercellular adhesion with the glutamine analogue 6-diazo-4 oxo-norleucine (DON), C-4I cultures on plastic and in suspension assumed forms resembling C-4II. On plastic, single 'basal' C-4II cells adhered more rapidly and migrated more slowly than C-4I cells, in keeping with the capacity of C-4II, but not C-4I, to secrete fibronectin (FN) substrata. However, on exogenous FN matrices, migration and cell dispersion were accelerated in both lines. Both lines expressed similar integrin profiles. Thus, the lines had diverged in extracellular matrix production, but not in the receptors for extracellular matrix components. The properties of the C-4 lines mimic those of specific cell types in normal stratified squamous epithelia, where intercellular adhesion increases but FN secretion diminishes with progression from the basal to the spinous stage of differentiation. Our results demonstrate a direct influence of differentiation-associated adhesive mechanisms on growth patterns and suggest that similar mechanisms may be responsible for variations in invasiveness among neoplastic clonal subpopulations. An awareness of these correlations may help to interpret the modes of local invasion by poorly differentiated carcinomas in terms of specific, well-defined cell properties. PMID- 1290034 TI - [Vasomotor disorders in the atherosclerotic coronary artery. Are there practical repercussions today?]. AB - The 1980s have brought increasing evidence that coronary vasomotricity has a major role in the pathophysiology of stable angina pectoris. Specifically, it has been shown that mediators such as serotonin have opposite effects on normal and atherosclerotic coronary arteries, resulting in vasodilation and increased coronary blood flow in the former and vasoconstriction with decreased flow in the latter. Other studies have shown that, even in patients with stable angina, coronary vaso-constriction is likely to trigger clinical episodes of angina. In this regard, the adjunction of coronary vasodilator medications to medications reducing myocardial demand might prove useful in patients with stable angina. PMID- 1290035 TI - [Hemostatic anomalies and coronary risk]. AB - The main role of thrombosis in the acute coronary event is now well documented. Numerous hemostatic factors are involved in thrombosis. Among them, fibrinogen, factor VII, leucocytes and platelets have been shown by epidemiology, to be closely related to the acute coronary event. The key role seems to be reserved to platelets since the close relationship of their activity as evaluated by platelet aggregation tests, to both coronary episodes and the main risk factors such as smoking, diabetes and dietary habits, has been recently demonstrated. In addition, the role of platelets has been confirmed by the marked protective effect against coronary events, of drugs such as aspirin, inhibiting platelet aggregation. PMID- 1290036 TI - [Thrombolytic agents in myocardial infarction: results of large mortality studies]. AB - Large studies involving several thousand patients have clearly established the effectiveness of thrombolytic therapy in reducing mortality in the acute phase of myocardial infarction: the earlier the treatment, the greater this reduction. The value of late thrombolysis remains to be determined by further studies. This technique can be extended to the oldest subjects who benefit most from this type of treatment, bearing in mind that they are at a greater risk of neurological complications. The effectiveness of thrombolysis is partially dissociated from its effects on left ventricular function. Since the thrombolytic agents (streptokinase, anistreplase and recombinant tissue plasminogen activator) are equally effective in reducing mortality and neurological complications, it seems reasonable to use the cheapest of these drugs as initial treatment, except in some special cases. PMID- 1290037 TI - [The promises of new antithrombotic agents]. AB - Most new antithrombotic drug development projects are focused on the improvement of myocardial infarction treatment at the acute phase. New thrombolytic drugs do not seem to be as attractive as adjunctive therapy, such as antiplatelet and antithrombotic agents, as well as inhibitors of thrombin generation. The current tendency is to select very specific molecules. The difficulty in developing these drugs must not be underestimated: they will be compared to very active drugs, such as aspirin, heparin or streptokinase; the therapeutic margin of antithrombotic therapy is very narrow; a clinical benefit will have to be shown. PMID- 1290038 TI - [Ischemic cardiomyopathy: remodeling, hypertrophy, subendocardial risk. Can processes be controlled?]. AB - Ischaemic cardiomyopathy reflects the myocardial dysfunction caused by coronary disease. It results from the association of 1. segmental infarction(s) responsible for ventricular "remodelling", i.e. expansion of the necrotic area(s) and hypertrophy-dilatation of the rest of the ventricle, eventually concurring to heart failure; 2. areas which are viable but with a function that is reversibly compromised by severe acute or chronic ischaemia (myocardial sideration or hibernation) affecting mainly the subendocardium. The spontaneous course of cardiomyopathy towards the worst can be arrested by 1. revascularisation of the myocardium at risk by coronary reperfusion performed either as an emergency in case of infarct in the process of formation, or after detection of the viable myocardial areas by isotopic methods; 2. prevention or limitation of ventricular remodelling by coronary reperfusion and improvement of the ventricular load by administration of angiotensin-converting enzyme inhibitors and nitroglycerin. The Survival and Ventricular Enlargement study (SAVE) has been the first to demonstrate the relationship between limitation of ventricular remodelling and improvement of the secondary prognosis of infarction obtained by angiotensin converting enzyme inhibitors. PMID- 1290039 TI - [Should coronary angiography be practiced in patients with recent myocardial infarction?]. AB - As a rule, infarction results from an occlusive thrombosis in a pre-existing atherosclerotic stenosis. Contrary to intravenous thrombolysis, coronary arteriography with immediate removal of obstruction can only be performed in a minority of patients. Similarly, "salvage angioplasty", performed if thrombolysis has failed, does not justify early coronary arteriography, except in certain cases of infarction at very high risk. In 80% of the cases the first days are uneventful, but the mortality in the first year (about 10%) will depend upon the presence or absence of latent residual ischaemia and/or left ventricular dysfunction. A noninvasive evaluation carried out before the patient is discharged and including clinical and echocardiographic data as well as the results of stress tests (sometimes coupled with isotopic studies) may isolate an important group of patients (40%) whose mortality rate at one year is below 3%. Systematic coronary arteriography, therefore, is not justified, especially since it facilitates the "easy" decisions of angioplasty the benefits of which has not been demonstrated in the absence of residual ischaemia during exercise. PMID- 1290040 TI - [Mishaps with anti-arrhythmic agents used to reduce mortality after infarction]. AB - The presence of isolated and/or repetitive ventricular arrhythmias following myocardial infarction identifies a group of patients at increased risk of death. The availability of anti-arrhythmic drugs, noticeably drugs with class I activity, efficient at suppressing arrhythmias has led to the hope that their administration could reduce post-myocardial infarction mortality. However, this hypothesis has not been confirmed. The Cardiac Arrhythmia Suppression Trial, which was designed to have the power to test the hypothesis that suppression of ventricular arrhythmias is associated with a decrease in mortality following myocardial infarction, even showed an increase in mortality with two drugs with class I activity. Several meta-analyses have confirmed that administration of class I antiarrhythmic drugs is of no clinical benefit in patients with non sustained ventricular arrhythmias following myocardial infarction. Ongoings studies are testing the hypothesis that such benefit could exist with amiodarone. The clinical benefit of beta-blockers, in terms of reduction of both total and sudden death post-myocardial infarction, has been clearly documented and mandates their administration in this setting. Futures studies of anti-arrhythmic drugs will have to focus on groups of patients at increased risk of arrhythmic death. PMID- 1290041 TI - [Role of physical effort in the monitoring of coronary disease: under medical treatment, after bypass, after angioplasty]. AB - Exercise tests must be performed only in hospitals and private clinics equipped for intensive care. Electrocardiographs must be fitted with a computer-assisted system for averaging and smoothing. In all but special cases it would be preferable to interrupt or delay the anti-angina treatment, so that the degree of ischaemia can be quantified. In this way, the severity of coronary lesions, the risk of arrhythmia and the prognosis for life can be predicted with good statistical certainty. In addition, the patient's fitness for work can easily be evaluated. As years go by, the ischaemia may be found to have become worse, and it might be decided to revascularize the myocardium in due course. Following revascularisation exercise tests are used to evaluate its benefits and follow their persistence. In addition, exercise tests are a very useful means of adjusting the antianginal treatment. Finally, exercise tests create a special link between patients and their medical team since they participate, both physically and psychologically, in their own diagnosis and evaluation of treatment. PMID- 1290042 TI - [Exercise echocardiography in coronary disease]. AB - Exercise echocardiography is a new method used in the investigation of coronary disease. It evaluates the repercussions on regional contractile function of the increase in oxygen consumption induced by physical exercise. It makes it possible to analyse in real time not only the amplitude of endocardial displacement, but also that of parietal thickening and thereby seems to be more precise than conventional ergonomic tests in the diagnosis of myocardial ischaemia. Its recent development owes much to the advent of digital technologies which make it easier and more accurate to interpret the changes observed in left ventricular regional kinetics by comparing the data at rest with those recorded at peak physical effort. When associated with an equally non-invasive ergometric test it is well accepted by the patients. Another of its advantages is its moderate cost. Echocardiographists must devote as much time as necessary to training. Training is indispensable to rapidly capture the images, particularly during efforts, and to reliably interpret the variations observed in left ventricular wall contraction. Exercise echocardiography is still under evaluation. Experience is lacking for the cardiologist to choose, only on its results, the most appropriate treatment for each individual patient, but its help will be appreciated in some difficult therapeutic decisions. Behind this phase of training for, and evaluating this technique several of its main clinical indications can already be outlined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290043 TI - [Hematopoiesis regulating factors. Important therapeutic future]. PMID- 1290044 TI - [Prescription of anticholinergic agents in the elderly. Potential dangers to be well aware of]. PMID- 1290045 TI - [Drug-induced nephropathies]. AB - Drug-induced nephropathies are frequent. Glomeruli, tubes, interstitium and arterioles may be altered. In this paper, we have tried to know if clinical, biological or histological signs of drug-induced nephropathies are similar or different from those observed in idiopathic nephropathies. We demonstrate that drug-induced nephropathies do not present any particular clinical or biological signs. We find that minimal changes and membranous glomerulopathies are the main lesions observed. In contrast, glomerular proliferations are very rare. Drug induced tubulopathies are characterized by tubular necrosis with variable extension. Interstitial lesions are absolutely identical to those observed in immunologically mediated nephropathies. Vascular lesions are very rare. It should be noticed that evolution of drug-induced nephropathies differs completely from idiopathic nephropathies. Indeed, renal lesions are usually regressive when the drug administration is stopped. In conclusion, it appears that drug-induced nephropathies mimic other forms of nephropathies. It is important to know that some drugs are excellent experimental models to reproduce some aspects of human renal pathologies. PMID- 1290046 TI - [Tricyclic antidepressive agents. Principles and rules for their use]. PMID- 1290047 TI - [Contraception. Methods, efficacy, choice, contraindications, monitoring, risks]. PMID- 1290048 TI - [Induced abortion. Legislation, epidemiology, complications]. PMID- 1290049 TI - [Dehydration. Etiology, physiopathology, diagnosis, treatment]. PMID- 1290050 TI - [Non-insulin-dependent diabetes. Epidemiology, etiology, physiopathology, diagnosis, complications, prognosis, treatment]. PMID- 1290051 TI - Adaptation and renewal in gastroenterology. Proceedings of a workshop. Interlaken, Switzerland, 20 June 1992. PMID- 1290052 TI - Adaptation and renewal of the gastrointestinal surgeon to meet the continuous challenge of modern gastroenterology. AB - The treatment of gastrointestinal diseases has entered into a period of rapid evolution. Gastroenterology has in the last 50 years evolved into a major specialty, covering not only complex clinical and diagnostic areas, but inclusive of sophisticated investigative work and major therapeutic endoscopic technology. Unfortunately, the evolution of gastrointestinal surgery has lagged behind. The scope of the gastrointestinal surgeon has become more limited, as potent pharmacotherapeutic probes, invasive radiological techniques and diagnostic and therapeutic endoscopic advances have been implemented. The development of minimally invasive surgical techniques has introduced a new era in surgical management. However, the establishment of new training programs and the acquisition of skills requiring the acquisition of costly equipment are major issues which surgical departments need to address. A novel training and programmatic configuration for the group of physicians involved in the management of gastrointestinal disease is required to meet this challenge. In particular, internists and surgeons must focus on the development of cost and time effective strategies for the management of clinical gastrointestinal disease. It seems likely, however, that adequate resources and management of these undertakings will only be forthcoming if corporate establishments, venture capital groups, medical health insurance institutions and national research agencies develop a consortium approach with medical schools to address these issues. PMID- 1290053 TI - Gastric acid in vertebrates. AB - Gastric secretion of hydrochloric acid appears to be unique to vertebrates and is almost ubiquitous in all fishes, amphibians, reptiles, birds and mammals. Comparative anatomy and physiology suggest that gastric acid has evolved approximately 350 million years ago. The similarity of the acid-secreting mechanism across all classes of vertebrates implies a major advantage for selection, but the evidence regarding its precise purpose remains inconclusive. PMID- 1290054 TI - Adaptation and renewal of the endocrine stomach. AB - At present at least seven different endocrine cell types have been identified in the stomach. According to their relative frequency and secretion products the antral gastrin producing G cell and somatostatin producing D cell and the fundic histamine producing ECL cell are the best characterized cell types. Total endocrine cell mass is controlled by various factors from inside and outside the stomach. Density of antral G and D cells depends on the presence and absence of food, on the antral pH and on additional humoral and/or neural factors. Gastrin and not gastric pH has been identified as the most important factor regulating the density of fundic ECL cells. Adaptation of gastric endocrine cells to gastric pH and to the presence, abundance or absence of humoral and neural regulators are well known phenomena though only partially understood. Antral G cells increase and antral D cells decrease during long-term achlorhydria which as a consequence leads to hypergastrinaemia. Examples are pernicious anaemia in man and drug induced acid suppression under experimental conditions. Interestingly, achlorhydria-induced G cell hyperplasia never progresses to gastrinomas. Fundic ECL cell density increases markedly in the presence of long-lasting hypergastrinaemia independently of gastric pH. In contrast to G cells ECL cell hyperplasia may progress to rarely occurring ECLomas. However, this depends on additional conditioning factors as the presence of severe atrophic gastritis as in pernicious anaemia or a specific genetic trait present in patients with gastrinomas associated with the MEN I syndrome. PMID- 1290055 TI - Does the stomach adapt to Helicobacter pylori? AB - To shed some light on the question of gastric adaptation to Helicobacter pylori infection, an overview is given of the various histopathological and clinical consequences of H. pylori infection in man. H. pylori infection can be considered as a chronic bacterial infection. For many individuals there is a balance between a low degree of infection and a low degree of inflammation. The microbial or host factors in adaptation of this balance are largely unknown. If and how 'downregulation' of the inflammatory/immune response does occur need further study. PMID- 1290056 TI - Gastric carcinoma: failed adaptation to Helicobacter pylori. AB - Helicobacter pylori is the major cause of chronic gastritis. Unlike bacterial infections in general, H. pylori acquisition causes a chronic, usually life-long infection. After acquisition, chronic inflammation (gastritis) appears and develops slowly into atrophic gastritis (with intestinal metaplasia) in a proportion of affected subjects. Inflammation and atrophy result from a failure of the immune system to eliminate the H. pylori infection. In infected stomach, several cascades of reactions are triggered which may result in impairments of structure and function of the gastric mucosa, some of which lesions also increase the risk of gastric carcinoma (CGA). A sequence of events from an early H. pylori infection into an atrophic gastritis has risen a theory that the H. pylori acquisition is a key issue in the development of GCA. Several aspects in the epidemiology and pathogenesis of GCA can be understood and explained by this infectious background. The H. pylori gastritis is unexpectedly common in patients with GCA of both intestinal or diffuse type, and the infection and gastritis precede the development of cancer. In Finland, 70-80% of the GCA cases seem to develop in connection with an H. pylori-positive gastritis or atrophy, 10-15% develop in a normal stomach (genetically determined GCA cases?), and 10-15% are associated with an H. pylori-negative corpus-limited (autoimmune) gastritis and atrophy. Case control studies suggest that the presence of H. pylori related inflammation raises the risk of GCA twofold, and the appearance of atrophic gastritis (and intestinal metaplasia) raises further this risk 2-3 times, as compared to the risk of GCA in subjects with a normal stomach. PMID- 1290057 TI - Adaptation of the gastric mucosa to stress. Role of prostaglandin and epidermal growth factor. AB - This study was designed to determine whether repeated exposures to stress lead to the adaptation of the gastric mucosa to stress ulcerogenesis. Wistar rats with intact or resected salivary glands were exposed to a standard period (3.5 h) of water-immersion and restraint stress every other day up to 8 days. The significant reduction in the severity of gastric lesions was first noticed after the second exposure to stress and was maximal after 6-day exposures to stress. This tolerance to stress ulcerogenesis disappeared after a 6-day rest during which animals were not exposed to stress. Histologically, the hemorrhages and edema seen after a single stress were less frequent during adaptation; instead the mucosa regenerated in spite of continuation of exposure to stress. During adaptation, the mucosal blood flow (MBF) and mucosal biosynthesis of PG were markedly increased. Administration of indomethacin (5 mg/kg i.p.) completely abolished gastric adaptation to stress and this was accompanied by about 85% reduction in mucosal generation of PG and significant decrease in the MBF. Salivectomy, which significantly reduced the luminal contents of epidermal growth factor (EGF) in the stomach, delayed and reduced the adaptation. We conclude that the stomach has the ability to adapt to repeated exposures to stress and that this adaptation is mediated, at least in part, by endogenous PG and EGF. PMID- 1290058 TI - Gastric adaptation to nonsteroidal anti-inflammatory drugs in man. AB - Adaptation describes the phenomenon in which visible gastric mucosal injury lessens or resolves completely despite continued administration of an injurious substance such as aspirin. Adaptation occurs in man although the mechanism remains unclear. Recent evidence suggests increased cell proliferation and correction of nonsteroidal anti-inflammatory drug induced reduction in gastric blood flow as possibly being important. Gastric erosions and ulcers in chronic nonsteroidal anti-inflammatory drug users represent failed adaptation. Gastric erosions and ulcers in chronic nonsteroidal anti-inflammatory drug users represent failed adaptation. The factors responsible for failure of adaptation are unknown but one clue is that there appears to be a dose-response effect relating anti-inflammatory dose and effectiveness of adaptation (i.e., adaptation is delayed, or less effective, when higher anti-inflammatory doses are administered). Gastric adaptation can be enhanced by co-therapy with synthetic prostaglandins but not with sucralfate or H2-receptor antagonists. PMID- 1290059 TI - Adaptation of gastric mucosa to chronic alcohol administration is associated with increased mucosal expression of growth factors and their receptor. AB - In our previous study we found that chronic, intragastric administration of ethanol to rats produces adaptation of the gastric mucosa to subsequent challenge with an acute dose of 50% ethanol. The mechanism of this mucosal tolerance remains unexplained. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) stimulate cells growth and proliferation in the gastric mucosa with noted trophic effect, protect the gastric mucosa against acute injury and accelerate healing of injured mucosa. Many of these effects are exerted through EGF and TGF alpha action on their common receptor (EGFR). The aim of the present study was to determine the effect of chronic alcohol administration on cell proliferation and gastric mucosal expression and distribution of EGF, TGF alpha and EGFR. Chronic administration of ethanol (1 ml, 50% ethanol, twice daily) significantly increased the extent of gastric mucosal mucous and proliferative cell zones, the number of proliferating (DNA synthesizing) cells and mucosal expression of EGF, TGF alpha and EGFR by 13, 6, and 20-fold, respectively. Thus, adaptation of gastric mucosa to chronic alcohol administration is associated with increased cell proliferation and increased expression of mucosal EGF, TGF alpha and EGFR. PMID- 1290061 TI - Adaptive mutagenesis--cause of alimentary cancer? AB - The tissues of the alimentary tract react to abnormal functional demands or to injury from environmental chemicals by reactions which involve change in morphology, functional characteristics and cellular proliferation. The work hyperplasia, wound repair or response to xenobiotics may become distorted by inherent, or induced, genomic abnormalities of the affected cells. It seems that some of the reactions are 'programmed' or 'planned' and depend on predetermined changes in gene expression. Although the reactions permit survival in the face of environmental hazards, the necessary alterations in gene expression may predispose to malignant change in the affected cells. PMID- 1290060 TI - Cellular and molecular basis of intestinal and pancreatic adaptation. AB - This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin like growth factor-I (IGF-I) mRNA in the intestine. PMID- 1290062 TI - Acid secretion, 1932-92: advances, adaptations, and paradoxes. AB - This paper reviews the evolution of our understanding of various aspects of gastric acid secretion over the past 60 years. Embryologic aspects and neonatal acid secretion are considered, and the relationship between parietal cell mass and acid secretion and the changing concepts of parietal cell activation are discussed. The effect of aging on acid secretion and the relevance of acid secretion in health and disease are reviewed, and current views on adaptation to therapeutic inhibition of acid secretion presented. The aetiologic link between acid secretion and ulcer disease is re-examined, and the role of pepsin, growth factors, and Helicobacter pylori briefly considered. PMID- 1290063 TI - Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. AB - Trefoil peptides are a growing group of proteins with interesting structural and functional properties. We have defined the pattern of trefoil peptide gene expression in the ulceration-associated cell lineage (UACL) and in the nearby mucosa in Crohn's disease. In the UACL, human spasmolytic polypeptide (hSP) mRNA is expressed in the acinar and proximal duct cells, while pS2 mRNA and peptide are found in the distal duct cells and in the surface cells. In adjacent mucosa, pS2 mRNA and protein are expressed by goblet cells, with the pS2 peptide concentrated in the area of the Golgi and also in the theca. Ultrastructural immunolocalisation showed the pS2 to be co-packaged in the mucous cell granules before being secreted into the intestinal lumen. In addition, pS2 peptide was demonstrated in local neuroendocrine cells and was also co-packaged with the neuroendocrine granules. The crypts associated with the UACL also showed marked neuroendocrine cell hyperplasia. We conclude that pS2 peptide is secreted locally into the viscoelastic coat covering the intestinal mucosa which surrounds Crohn's disease ulcers. In addition, it is clear that intestinal goblet cells, in addition to producing mucins, are a rich source of regulatory peptides. Moreover, pS2 is clearly co-packaged with neurosecretory granules, which are released through basal and lateral membranes so that the contained peptides can act in a paracrine manner. These findings are interpreted in terms of the epidermal growth factor/urogastrone released by the UACL, stimulating pS2 gene expression in surrounding cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290064 TI - Adaptation in the pharmaceutical industry, with particular reference to gastrointestinal drugs and diseases. AB - In terms of gastrointestinal diseases, the pharmaceutical industry is having to adapt in the face of great success (e.g. anti-ulcer drugs), continued failure (e.g. cancer therapy) and increasing commercial pressures. Whilst success is evident by the presence of four anti-ulcer agents in the top 25 best-selling drugs, the GI tract remains the major site of cancer, a disease where almost no progress in drug treatment has occurred since the discovery of anti-metabolites. In addition to being a major therapeutic target, the GI tract is also the principal route of drug administration with some one hundred billion unit dosages being ingested per year. Not surprisingly, therefore, the gut reigns supreme as a site of minor side-effects. More serious adverse reactions are also common and those associated with anti-proliferative and anti-arthritic drugs can be life threatening. Thus an agent to combat adverse GI reactions represents a drug development opportunity in itself. In terms of primary diseases of the gut, the pharmaceutical industry is having to adapt to the uncertainties inherent in developing drugs in markets which are poorly defined because of the absence of effective treatments. Foremost amongst these are neoplastic and inflammatory diseases. Although these represent formidable targets, clinical needs and consequently commercial success would far outweight any gains from developing another generation of anti-ulcer drugs to compete with existing anti-secretory agents. PMID- 1290065 TI - Adaptation of mitochondrial metabolism in liver cirrhosis. Different strategies to maintain a vital function. AB - Mitochondrial function and structure in cirrhotic livers from humans or rats show a variety of changes as compared to control livers. Mitochondrial ATP production is reduced in rats with CCl4- or thioacetamide-induced liver cirrhosis and in rats with secondary biliary cirrhosis. Activity of the electron transport chain is decreased in rats with secondary biliary cirrhosis. In rats with CCl4-induced cirrhosis, the mitochondrial content of certain constituents of the respiratory chain (cytochrome a + a3, cytochrome b and ubiquinone) is increased and activities of cytochrome c oxidase and ATPase are elevated. Similarly, in humans with liver cirrhosis, mitochondrial cytochrome a + a3 content is elevated and has been used to assess the risk for hepatectomy. In rats with secondary biliary cirrhosis, compensatory strategies include increased mitochondrial volume per hepatocyte and possibly increased extramitochondrial ATP production (increased glycolysis). Thus, a variety of adaptive mechanisms are used to maintain mitochondrial function in cirrhotic livers. PMID- 1290066 TI - Adaptation and change in gastroenterology. AB - Predicting the future is a chancy business. In line with other medical specialties, gastroenterology will be subject to rapid and profound changes in the coming decades and will have to adapt and renew its approach to the way medicine will be practised. The pressures to change will be in several areas. Global demographic, political and economic factors will become more intrusive and rapid communication will end isolationism. Developing EC structures and regulations are likely to increase mobility of medical staff and uniformity in the standards of training and practice. Rapid technological advances will have to be reconciled with finite resources and the ever increasing expectations of our aging population. PMID- 1290067 TI - Congenital toxoplasmosis. Copenhagen, January 17, 1992. Proceedings. PMID- 1290068 TI - Congenital toxoplasmosis: is screening desirable? AB - Toxoplasmosis, a disease caused by the parasite Toxoplasma gondii, is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity and even death. Moreover, there is increasing awareness that congenital toxoplasmosis can cause blindness, epilepsy and other abnormalities in children and adults. Congenital toxoplasmosis can only be prevented by giving information on how to avoid the infection during pregnancy or by routine serologic screening of pregnant women to identify a recent toxoplasma infection that would allow a timely decision for antibiotic treatment and prenatal diagnosis. Advice to pregnant women to apply hygienic measures during pregnancy can reduce with 63% the toxoplasma infection rate during pregnancy and should therefore become standard obstetrical care. Adequate serological screening for toxoplasmosis is possible and allows selection of patients at high risk for delivering a congenitally infected child. Prenatal diagnosis is accurate in diagnosing correctly infected fetuses around the 20th week of gestation. Whether or not serologic screening for toxoplasmosis should be combined with primary prevention will depend on the incidence of congenital toxoplasmosis in a given geographic area. PMID- 1290069 TI - Diagnosis of Toxoplasma infection in the pregnant woman and the unborn child: current problems. AB - Prevention of congenital toxoplasmosis requires identification of non immune women at the beginning of pregnancy, instruction on how to avoid contamination and a serological follow-up of the women until the delivery. The latter is easily achieved by a repeated testing for specific IgG and IgM. Most of the interpretation difficulties arise from results suggestive of recent infection obtained on a first specimen. If no rise in IgG titer is demonstrated on a second serum sample, the use of additional tests studying other Ig-isotypes or acute phase IgG antibodies can be helpful, mainly as a way to exclude the possibility of infection acquired during pregnancy. Congenital infection can be investigated by biological measurements on fetal blood and by ultrasound examination. Detection of specific IgM and IgA in fetal serum must be interpreted with care because of the existing risk of contamination with maternal blood. Demonstration of Toxoplasma gondii in fetal blood or amniotic fluid by mouse inoculation definitely proves the diagnosis; though less sensitive, tissue culture offers the advantage of a more rapid result. The very promising results obtained by the PCR method applied to amniotic fluid samples give the hope that it can replace som of the existing confirmatory methods. PMID- 1290070 TI - Treatment of toxoplasmosis in the pregnant mother and newborn child. AB - The paper presents a review of different treatment regimens employed for 25 years to prevent and treat congenital toxoplasmosis. Unfortunately, no well-controlled, randomized trials have been performed to evaluate the efficacy of different therapies of pregnant women or infected neonates. Treatment in pregnancy may be effective since transplacental passage of parasites is delayed. Spiramycin, a complete safe drug which concentrates in the placenta, may reduce the risk of materno-fetal transmission by 60%, but is in the present doses without influence on an already infected fetus. Pyrimethamine in combination with sulfonamides erradicates more effectively parasites in the placenta, and also in the fetus. Today a combination of both regimens is recommended in pregnancy. As for the infected neonates, intensive treatment of pyrimethamine/sulfonamides alternating with spiramycin until one year of age seems to prevent development of late appearing sequelae. There is obviously a need for international multicenter studies to settle the optimal schedules and duration of therapy which again is highly dependent on the performance of an appropriate serological screening during pregnancy. PMID- 1290071 TI - Prevention of prenatal toxoplasmosis by serological screening of pregnant women in Austria. AB - In 1975 Austria introduced an obligatory serological screening of pregnant women for toxoplasmosis. Every woman is tested for antibodies at the beginning of her pregnancy and, in case of seronegativity, again in the second and third trimester. Basic tests are--alternatively--Dye test (SFT) and Indirect Fluorescent Antibody test IFAT); for further clarification, complement fixation test (CFT) and, particularly, various tests for detection of specific IgM and IgA antibodies and, in certain cases, for circulating antigen are carried out. If a primary Toxoplasma gondii infection of the pregnant woman is suspected, immediate therapy--with spiramycin before the 16th week of gestation and with pyrimethamin plus sulfadiazin after the 15th week of gestation--is carried out. Before the introduction of the screening programme, the incidence of prenatal toxoplasma infections was 50-70 per 10,000 births, presently it is below 1 per 10,000 births. Seropositivity among pregnant woman has decreased from almost 50% at the end of the seventies, to 36.7% in recent years (1989-1991). The percentage of suspected primary infection during pregnancy has, however, in the same period increased from less than 0.4% to 0.83%. PMID- 1290072 TI - Screening for toxoplasmosis in pregnant women: presentation of a screening programme in the former "East"-Germany, and the present status in Germany. AB - The results of the screening programme (including the examination of fetal IgM) in East-Germany, related to the efficiency of therapy (pyrimethamine/sulfonamid) of the fetal infection risk are presented. For comparison the results of a prospective study of toxoplasmosis in pregnancy (n = 1697) without therapy, and follow up of the connatal infected infants to the age of 9/10 years old are shown. Recommendations for the diagnostic and therapeutical management in Germany for the future are presented. PMID- 1290073 TI - Screening programme for congenital toxoplasmosis in France. AB - The high prevalence of Toxoplasma gondii infection in France led to the establishment of a national screening programme. Preventive measures were progressively introduced, and these became compulsory in 1978 with the result that the incidence of congenital toxoplasmosis is now markedly reduced. Further improvements may include more systematic sampling from women before pregnancy, better and adequate health education and centralized notification of both maternal and congenital cases of toxoplasmosis. PMID- 1290074 TI - Cord blood screening for congenital toxoplasmosis: detection and treatment of asymptomatic newborns in Basel, Switzerland. AB - Cord blood screening is a helpful tool for the detection of infants probably infected with Toxoplasma gondii, if serological data of the mothers are not available. Testing for toxoplasma specific IgM and IgG antibodies of about 30,000 cord blood sera gave information about the changes in prevalence and incidence of toxoplasmosis in pregnant women in Basel between 1983 and 1991. The follow up and treatment of the infected children revealed the need of a randomized study comparing high and low dose treatment schedules. PMID- 1290075 TI - Choices in preventive strategies: experience with the prevention of congenital toxoplasmosis in The Netherlands. AB - The control congenital toxoplasmosis mainly relies on preventive measures, that can be applied on an individual basis as well as within the scope of a collective preventive programme. Several strategies can be adopted, each with its possibilities and impossibilities: primary prevention (health education), secondary prevention (serological screening) or a combination of primary and secondary prevention. Whatever strategy is chosen, decisions have to be taken with respect to the procedures. This paper lists the choices to be made and their consequences. The debate in international literature on the desirability of preventive programmes is summarized. PMID- 1290076 TI - Newborn screening for congenital Toxoplasma infection: five years experience in Massachusetts, USA. AB - Since 1986, all Massachusetts newborn filter paper blood specimens, and some from New Hampshire, have been screened for the presence of IgM antibodies to Toxoplasma gondii using an enzyme-linked IgM capture assay. Among approximately 530,000 infants screened, 40 had serologically confirmed congenital toxoplasma infection, and 4 additional infants had borderline serologies, for an overall identification and treatment rate of 1:12,000. False positive results from the newborn's filter paper specimen occurred in 22 infants (1/24,000); these were clarified by tests for IgM and IgG in serum specimens obtained 2-3 weeks later from the infant and mother. The screening program would have failed to detect 3 infants with severe infection who were diagnosed on clinical grounds prenatally or at birth and lacked IgM. No infants with a later diagnosis of congenital toxoplasmosis that was missed by screening are known to our statewide network of pediatric infectious disease consultants. Follow-up studies are in progress to evaluate more completely the sensitivity of the IgM assay in newborns and the efficacy of treatment. PMID- 1290077 TI - Epidemiology of toxoplasmosis in the U.K. AB - The overall rate of toxoplasma infection in the U.K. is between 23-33% though there is evidence of regional variation. Seropositivity increases by 0.5-1.0% per annum to reach about 50% at the age of 60 years. The incidence of acute infection in pregnant women is about 2-2.6% per thousand pregnancies while the transplacental transmission rate is reported to range from 0% to 40%. As there is no official notification of congenital toxoplasma infections within U.K. the true number of cases is not known. However, information relating to the prevalence of infection in the general population in the U.K. is outdated and new studies are urgently required. PMID- 1290078 TI - Prenatal and neonatal screening: status and future trends. PMID- 1290079 TI - The program for antenatal screening of toxoplasmosis in Finland: a prospective cohort study. AB - 16,733 pregnant women were studied for toxoplasma specific antibodies during an 18-month period. The number of specimens was 44,181. The IgG seropositivity of mothers was 20.3%. The incidence of primary toxoplasma infections during pregnancy was 4.2 per 1000 seronegative pregnancies by using the traditional criteria, IgG seroconversion and/or a positive IgM. By using the IgG activity test as an additional criterion, the incidence was 2.4 per 1000 seronegative pregnancies. Due to transmission rate of 40%, the number of congenital toxoplasma infections in Finland is more than 50 per year. The evaluation is going on and the cost-benefit analysis will reveal the effectiveness of antenatal screening. PMID- 1290080 TI - Neonatal screening for congenital toxoplasmosis in Denmark: presentation of the design of a prospective study. AB - The design of a two year prospective study of 45,000 mothers and their newborn children aiming at determining the incidence of congenital toxoplasmosis in Denmark is presented. Toxoplasma IgG antibodies in a bloodspot from the newborn, routinely collected on filterpaper (the Guthrie card), and IgG antibodies in a stored serum sample from the mother collected in the first trimester are compared. Seroconversion identify mothers infected with T. gondii during pregnancy and identify newborn children at risk of congenital toxoplasmosis. All children at risk will be treated and followed until congenital toxoplasmosis is verified or excluded. Children with verified congenital toxoplasmosis will be followed clinically and the effectiveness of the treatment will be evaluated. The study design allows determination of the materno-fetal transmission rate in untreated pregnancies, and will furthermore allow a good estimate of the incidence of congenital toxoplasmosis in Denmark. In addition we hope that the diagnosis and treatment of cases of subclinical toxoplasmosis will prevent chorioretinitis and minor cerebral disorders later in life. Of 6355 pregnancies tested during the first 3 month of the study, 14 cases of maternal seroconversions have been diagnosed. Only one child had detectable toxoplasma specific IgM antibodies at birth. PMID- 1290081 TI - Current status of toxoplasmosis in pregnancy in Norway. AB - The paper reports previous epidemiologic data obtained in Norway and describes briefly the design of a prospective study of primary toxoplasma infection which will be carried out among pregnant women in Norway in the period 1992-1994. PMID- 1290082 TI - Twenty-two years screening for toxoplasmosis in pregnancy: Liege-Belgium. AB - Between 1966 and 1987, in Liege--Belgium, 20,901 pregnant women were screened for toxoplasmosis. In this period an increase in seronegative women from 30% to 53% and a decrease in the seroconversion rate from 6.4% to 1.2% was observed. This decrease could be the result of advice and prophylactic measures. Due to the low rate of seroconversion (actually less than 1%), the cost/effectiveness of a systematic screening and fetal diagnosis should be investigated. PMID- 1290083 TI - Economic evaluation of preventive programmes against congenital toxoplasmosis. AB - Benefit-cost analysis are applied to different strategies aimed at preventing congenital toxoplasmosis. The first strategy involves health education of pregnant women on how to avoid toxoplasma infection. The second strategy comprise serological surveillance in pregnancy combined with prenatal diagnosis and chemotherapy. The cost of health education is less than the cost of the serological screening, but health education will most likely lead to a haphazard testing of individuals and thereby increasing the cost. The best and most rational approach, and the programme which will prevent most cases and save most money for the society, is a combination of both programmes. Compared with the results of any of the two strategies alone, the benefits of the combined programme will increase significantly, while the cost (NOK 165 per participating woman) will only add fractions to that of the serological screening programme. The benefits of the strategies are influenced by many uncertain factors such as the discount rate, the incidence of infection, the intrauterine transmission rate, the outcome of pregnancy, the prognosis of the offspring, the sensitivity of the screening tests and the effectiveness of the programme. After applying a sensitivity analysis, both programmes were found to be of economic benefit to society at an incidence of maternal toxoplasmosis of 1-1.5 per 1000. Thus the pilot screening initiated in Norway to determine the incidence of infection, seems justified. PMID- 1290084 TI - Intravesical instillation of drugs in patients with detrusor hyperactivity. AB - Intravesical administration of drugs may inhibit detrusor hyperactivity. Intravesical drug administration might be clinically useful in patients with detrusor hyperactivity, particularly in patients with neurogenic etiology using CIC. The therapeutic usefulness has to be documented in controlled studies. The mechanisms of action and the potency of the individual substances can not be decided from the present investigations. However, no finding contradicts that the known pharmacological properties of the drugs used are responsible for the effects noted. The different responsiveness to intravesical drugs between patients with neurogenic and non-neurogenic etiology might be due to pathophysiological differences. By intravesical administration of drugs the tissue concentration obtainable within the bladder wall is higher than the one obtainable by systemic administration. The optimal relation between tissue and serum concentrations can be achieved by a careful preparation of the drug solution and by titration of the dose. No side effects were found in the studies and no clinically significant side effects have been reported by other investigators. The risk of late side effects is unknown. The serum concentrations found in man and rabbit, after intravesical instillation of terodiline, indicate that by this route of administration terodiline may be safely used, in spite of the side effects reported at systemic administration. For evaluation of the diagnostic usefulness further documentation of the mechanisms of action and of the pathophysiology are needed. PMID- 1290085 TI - [Ultrasonic diagnosis of bile duct calculi. A prospective study regarding the effects and the objective and subjective factors on accuracy in choledocholithiasis]. AB - The reliability and diagnostic sensitivity of the sonographic identification of bile duct concrements is mainly determined by the examiner's competence and the size of the concrements, and secondly also by the diameter or patency of the bile ducts. Basing on the records of 175 patients on whom choledocholithiasis had been performed, a prospective study (reference: concrement removal after ERCP) showed that the sensitivity of the method is almost twice as high with an experienced examiner than with a less experienced physician (80% vs. 47%). In 231 other cases with extrahepatically conditioned cholestasis we found a 93% specificity of sonography in respect of excluding the presence of concrements. 93% of the concrements that were bigger than 10 mm were definitely diagnosed via sonography (71% sensitivity in case of concrements < 10 mm). If the proof of presence of concrements is differentiated according to bile duct width, it is seen that 85% of all concrements were visualised if the width of the ductus choledochus was > or = 8 mm and 71% in case of a width < 8 mm. The results of the study justify the use of sonography as a primary method in the diagnosis of concrements of the bile ducts; under certain conditions it is also possible to exclude the presence of stones. If findings do not agree with the clinical pattern of findings, or if the bile ducts cannot be visualised properly, diagnostic ERCP is indicated. PMID- 1290086 TI - [Sonography and biliary extracorporeal shockwave lithotripsy (ESWL)]. AB - Ultrasound is an indispensable tool for preliminary diagnosis ("filter function"), during treatment ("monitoring function") and in the follow-up examinations ("follow-up function") after shock-wave lithotripsy of gallstones. It permits rapid and reliable assessment of the therapeutic outcome and early identification of complications, which present-day experience has shown to be rare. PMID- 1290087 TI - [Endosonography in chronic pancreatitis. A comparative study of endoscopic retrograde pancreatography and endoscopic sonography]. AB - EUS and ERP were performed in 114 patients. 94 patients (32 women, 62 men; mean age 53 years; range 29-78 years) had inflammatory pancreatic disease while 20 patients (6 women, 14 men; mean age 54 years; range 28-78 years) without disease of the pancreas served as controls. ERP-findings served as the gold standard and were classified into stages I-III according to the Cambridge classification. On ERP 51 patients had duct changes typical of chronic pancreatitis (CP). Control cases always displayed a homogeneous echo pattern and a regular outer margin of the pancreas. Abnormal EUS findings were present in all patients with ERP-stages II and III and in 88% of patients with ERP-stage I. 63% of patients with a normal pancreatogram, i.e. ERP-stage 0 showed pathological alterations on EUS examination. Diffuse alterations of the echopattern were seen in 75% of CP patients with stage I, in 88% with stage II and in 96% with stage III. Alternating echo-poor/echo-dense areas were present in 50% of stage I, in 88% of stage II, and in 81% of stage III cases, respectively. 38% of stage I, 56% of stage II, and 27% of stage III cases displayed a lobulated appearance of pancreatic parenchyma. In 80% of the patients these findings were combined with an irregularly lined pancreatic surface. This same combination of EUS-findings in proven CP was also present in 30% of patients with completely normal pancreatic ducts, i.e. ERP-stage 0. Changes of the main pancreatic duct in stages II and III were also seen with EUS in 81% and 96%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290088 TI - [Value of duplex sonography in diagnosis of renal artery stenosis and its value in follow-up after angioplasty (PTA)]. AB - The assessment of the renal arteries is particularly important in the detection of a renovascular cause of the arterial hypertension. The purpose of the present study was twofold: to evaluate the accuracy of duplex scanning in non-invasively diagnosing renal artery stenoses in hypertensive patients, and to determine the results of transluminal angioplasty of renal artery stenoses as assessed by duplex scanning. In 76 patients with arterial hyertension, 170 renal arteries (18 kidneys supplied by two renal arteries) were examined by both duplex scanning and angiography (DSA in intraarterial and intravenous technique, and conventional arteriography). Peak systolic and end-diastolic flow velocity parameters as well as the Pourcelot-index were determined in the proximal renal artery and compared with the indendently performed angiography. In 102 angiographically proven normal renal arteries, mean +/- SD peak systolic and end-diastolic velocity values were 84.7 +/- 13.9 cm/s and 31.2 +/- 7.8 cm/s, respectively, with a Pourcelot-index of 0.66 +/- 0.07. For detecting renal artery stenoses greater than 50%, duplex scanning had a sensitivity of 86%, and a specificity of 83% for a systolic peak velocity of 140 cm/s and more in the renal artery. In 13 patients with 14 stenosed renal arteries, duplex scanning and intraarterial DSA densitometry were performed before and after transluminal angioplasty of the renal artery stenoses. There was fairly good agreement between transstenotic peak systolic velocities and densitometrically determined degrees of stenosis in the renal artery (r = 0.84). These results show that duplex scanning is an accurate noninvasive diagnostic tool in detecting proximal renal artery stenoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290089 TI - [Pulsatile flow model with elastic blood vessels for duplex ultrasound studies]. AB - Using ultrasound duplex technique flow phenomena in patients' circulation can be examined. For the interpretation of these examinations it is necessary to have extensive knowledge on flow influencing parameters. This can be easily obtained from simplified flow models. This article describes the components of a flow model that allows examination of ultrasonic contrast media flowing through an artificial heart and vessel mimicking tubes. The artificial heart is the drive which pumps a water glycerol cellulose mixture through the circulation in a pulsatile manner. The shape of the ventricle, the compliance of the aorta, the viscosity of the flow medium and the wall elasticity of the examination vessel were taken into account. The attenuation caused by the surrounding tissue is simulated by a variable layer of castor oil. The flow model is suitable to produce flow profiles that are very similar to physiological profiles. PMID- 1290090 TI - [Written documentation of ultrasound findings. A contribution to rationalization and standardization: how should a report of ultrasound findings be organized?]. AB - A system for documentation of ultrasonographic findings is presented. Characteristic items and features of a report are defined. PMID- 1290091 TI - [Ultrasonic diagnosis of goiter of the tongue base]. AB - Lingual goitre was found in two adolescents suffering from mild dysphagia. Since there were typical changes in lingual sonomorphology, sonographic evaluation was easy to perform. Lingual thyroid was less echogenic than normal thyroid tissue. Ultrasound may support the decision of the initial treatment and is useful to guide further therapy. PMID- 1290092 TI - [Ultrasonic diagnosis of so-called "occult" testicular tumor]. AB - A 40-year old man complaining of severe pain in the right mid-abdomen, nausea and vomiting was brought to the casualty department. Sonography revealed retroperitoneal masses in the right mid-abdomen and the left lower abdomen. These masses were confirmed by computed tomography and lymphography to be lymph node metastases. In the smaller right testis, in which a tumour was not suspected, a hypoechoic region was identified, which on histological examination after orchiectomy proved to be a pure seminoma. PMID- 1290093 TI - [Simple health problems without simple solutions]. PMID- 1290094 TI - [Difficulties with consent]. PMID- 1290095 TI - [The doctor, the patient and the interpreter]. PMID- 1290096 TI - [Nursing care for asylum seekers]. PMID- 1290097 TI - [Public health management of an ethnically and culturally diverse population]. PMID- 1290098 TI - [Immigrants must face pathologies in their new countries]. PMID- 1290099 TI - [The pathology of the transplanted black African]. PMID- 1290100 TI - [Filariasis]. PMID- 1290101 TI - [Amebiasis]. PMID- 1290102 TI - [Bilharziasis]. PMID- 1290103 TI - [The waterfall of frontiers. Voyage into the heart of an exile]. PMID- 1290104 TI - [Malaria]. PMID- 1290105 TI - [Thalassemias and sickle cell anemias]. PMID- 1290106 TI - [Nursing management of a child with sickle cell anemia]. PMID- 1290107 TI - [Tuberculosis: answers and perspectives]. PMID- 1290108 TI - [Cecile Boisvert: nursing diagnoses have made progress. Interview by Francoise Henin]. PMID- 1290110 TI - [Blood expander solutions]. PMID- 1290109 TI - [Penury of nursing personnel in France]. PMID- 1290111 TI - [Insertion of a short venous catheter with an anti-reflux valve]. PMID- 1290113 TI - [Biomedical bases of chronobiology]. PMID- 1290112 TI - [Stories of exile]. PMID- 1290114 TI - [Use of the Intelliject infusion pump in anti-cancer chronobiology]. PMID- 1290115 TI - [Chronobiology in home nursing]. PMID- 1290116 TI - [The pain of nurses]. PMID- 1290117 TI - [The organization of care and the waiting of patients]. PMID- 1290118 TI - [Quality of life and malignant hemopathies]. PMID- 1290119 TI - [Organization and management of an ambulatory, continuous chemotherapy unit]. PMID- 1290120 TI - [Evolution of medical oncology]. PMID- 1290122 TI - [To calm by calming oneself. Interview by Francoise Henin]. PMID- 1290121 TI - [Anorexia in the cancer patient]. PMID- 1290123 TI - [Myocardial infarction. Four hours to save a heart]. PMID- 1290124 TI - [Communicating to optimize the potentials of the patient care team. The evaluation interview]. PMID- 1290125 TI - [Glycopeptide antibiotics]. PMID- 1290126 TI - [Thermotherapy in oncology]. PMID- 1290127 TI - [Preparation of a programmed infusion pump for timed chemotherapy]. PMID- 1290128 TI - [To rediscover liberty under constraint?]. PMID- 1290129 TI - [Sectionalized care]. PMID- 1290130 TI - [Ethics and psychotherapy]. PMID- 1290131 TI - [Ethics and relations with families]. PMID- 1290132 TI - [Nursing specialization in psychiatric care: elements of reflection and propositions]. PMID- 1290133 TI - [Ethics and psychiatry]. PMID- 1290134 TI - [Nursing diagnosis]. PMID- 1290135 TI - [Sakel's cure]. PMID- 1290136 TI - [For ethics in psychiatric care]. PMID- 1290137 TI - [Psychosomatic man]. PMID- 1290139 TI - [General ethics in nursing care]. PMID- 1290138 TI - [Early dementia]. PMID- 1290140 TI - [The consent for care]. PMID- 1290142 TI - Anatomic basis of pronator quadratus flap. AB - The pronator quadratus m. can be raised as a flap on its main anterior interosseous pedicle, whose characteristics are as follows: diameter of the artery 2.1 mm, diameter of the each of both veins 2.4 mm, length of useful pedicle 70-80 mm, after possible intraneural dissection of the nerves to the flexor pollicis longus m. PMID- 1290141 TI - Representation of the human body: the colored wax anatomic models of the 18th and 19th centuries in the revival of medical instruction. PMID- 1290143 TI - Preparation of four-color arterial corrosion casts of the laryngeal arteries. AB - The supply areas of the superior and inferior laryngeal arteries were studied in order to plan tissue-sparing laryngeal surgery. Arterial corrosion casts with and without preservation of the laryngeal skeleton were prepared and the supply areas of the superior and inferior laryngeal arteries were distinguished from each other by injecting differently colored methacrylates. The ramifications of the laryngeal arteries could be classified clearly in the macerated specimens which preserved the laryngeal skeleton. PMID- 1290144 TI - Rotation-abduction analysis in 10 normal and 20 pathologic shoulders. Elite system application. AB - Kinematics of shoulder rotation-abduction in the plane of the scapula were analysed using the Elite system. We evaluated 10 asymptomatic subjects and 20 patients with painful conditions affecting the shoulder, 10 adhesive capsulitis and 10 rotator cuff-tears. The last pathologic cases were reexamined after rehabilitation treatment. The Elite system computed on line the trajectories of 8 retro reflective markers glued on the main reference points (3 on the spine, 3 on the scapula and 2 on the humerus). Angles and linear velocities were also evaluated. The lower humeral site displacement and gleno-humeral angle increase allowed differentiation of the normal shoulder rotation-abduction from the abnormal movement. Hence, rehabilitation progress could be followed up. PMID- 1290145 TI - Growth of the human metatarsal bones in the fetal period (13-24 weeks postconception): a quantitative study. AB - We studied metatarsal growth in 600 metatarsal bones (60 pairs of feet) taken from 60 human fetuses (35 males and 25 females) ranging in age from 13 to 24 weeks postconception. The data obtained for the total length (TL) and for the ossified metatarsal length (OML) were correlated to fetal crown-rump length (C R). The ossified metatarsal length presented a growth rate greater than the total length growth rate. There was no statistical difference between either the right and left metatarsals or males and females in total length and ossified metatarsal length growth during the period studied. We believe that metatarsal growth curves could be used to monitor fetal foot growth. PMID- 1290146 TI - The ramification of the superficial branch of the superior gluteal artery. Anatomical basis of a new gluteus maximus myocutaneous flap. AB - In order to design a new gluteus maximus myocutaneous flap, the ramification of the superficial branch of the superior gluteal artery was investigated in 56 sides of 33 Japanese cadavers. The superficial branch constantly divides into two main branches, which are called the ascending and transverse branches in this study. Of the ascending and transverse branches, one or both usually give off at least one well developed division running on the undersurface of the gluteus maximus muscle (98.2%). This division, which is called the intermediate branch in this study, generally reaches the superior edge of the muscle giving off only a couple of muscular branches and pierces the muscle and its deep fascia to supply skin (83.6%). Perforators of the intermediate branch constantly emerge from the fascia near the middle or lower one-third point on a line extending from the middle of the iliac crest to the tip of the greater trochanter. PMID- 1290147 TI - The thenar muscles. New findings. AB - Examination of the thenar muscles in 30 anatomical preparations of the hand have shown that the abductor pollicis brevis, the opponens pollicis, and the adductor pollicis muscles are made up of several muscle bellies. The number and insertions of these bellies are varied. Both heads of flexor pollicis brevis do not originate from any particular muscle belly. The superficial head of this muscle always inserted into the head of the thumb metacarpal, either completely, or, some of the fibres of the dorsal aponeurosis of the thumb were attached to the base of the proximal phalanx. Furthermore the anatomy of the abductor pollicis brevis muscle was related to the presence of a tendinous slip from abductor pollicis longus. These variations could have an influence on proprioception in the thumb ray. PMID- 1290148 TI - Fascial layers of the scalp. A study of 48 cadaveric dissections. AB - The arrangement and structure of the fascial layers of the scalp were studied in 48 red neoprene latex-injected cadavers with the aid of an operating microscope. The galea aponeurotica was continuous with a superficial temporal fascia. Deep to the galea, the subaponeurotic connective tissue was bilaminar. There was an outer, vascular, areolar layer, and an inner, avascular, membranous layer. Underlying the temporalis muscle, the pericranium was thinner and more adherent than elsewhere with no subpericranial tissue. PMID- 1290149 TI - Radiologic anatomy of the paranasal sinuses in the child. AB - The development of the paranasal or accessory sinuses begins very early in utero. In the newborn the ethmoidal sinus, which gives rise to all the other sinuses, as well as the maxillary sinus, can already be identified on x-rays. The frontal sinus appears as a triangle at the age of four and oversteps the supraorbital margin at the age of six. The sphenoidal sinus begins to excavate the concha sphenoidalis at the age of four and can be seen on x-rays at the age of eight, when it extends to the hypophyseal fossa. In the twelve-year-old child all sinuses almost reach their final sizes. However, the size and shape of all sinuses, particularly of the frontal and the sphenoidal sinuses are very different. PMID- 1290150 TI - Bi- and three-dimensional CT study of carpal bone motion occurring in lateral deviation. AB - A computed tomography (CT) study of the right wrists of 15 volunteers and of 5 anatomical preparations in neutral position, radial (15 degrees) and ulnar (30 degrees) deviation enables to tackle the qualitative analysis of carpal bone motion. The CT Scans were analyzed and reconstructed in three dimensions by means of the Philips CAMRA S100 computer program. The results show that the capitate, the metacarpals II and III and, to a lesser extent, the trapezium and the trapezoid are poorly mobile. Our study points to the role of the flexor and extensor carpi ulnaris muscles in the stability of the internal carpus, confirming that the pisiform is a sesamoid bone in the flexor carpi ulnaris tendon. A model of longitudinal functional structure of the carpus during lateral deviation, intermediate between those of Navarro and Taleisnik, is proposed. PMID- 1290151 TI - High resolution MRI of the normal finger at 0.1 T: anatomic correlations. AB - MR images of the fingers are obtained in a 128 x 128 or 256 x 256 matrix format using a prototype of a mini imager dedicated to the hand. The vertical field of 0.1 T is provided by an electro-magnet with an air gap of 15 cm equipped with a single solenoidal coil. No Faraday cage is used. The maximum in plane pixel resolution of 100 mu is obtained for a field of view of 2.5 cm with a slice thickness of 2 mm. The identification of fine structures of the finger is demonstrated by the anatomical and histological correlations. This type of imager which is adapted to very limited field of views demonstrate that high resolution MRI of limb extremities can be achieved at 0.1 T. PMID- 1290152 TI - Retroaortic left renal vein: a report of six cases. AB - Six cases of retroaortic left renal vein have been studied, two in corpses and four by means of Computed Tomography. Any previous pathology has been rejected. The total number of dissected specimens was 116, whereas the patients with non pathological retroperitoneum studied by CT numbered 170. In our six cases, the left renal vein formed a single trunk of considerable size, retroaortic position and directed obliquely towards the inferior vena cava. PMID- 1290153 TI - Avian model for 13-cis-retinoic acid embryopathy: morphological characterization of ventricular septal defects. AB - In developing an avian model for 13-cis-retinoic acid (13cisRA) embryopathy, we found 13cisRA induced cardiovascular defects, especially Type I ventricular septal defects (VSDs) (Hart et al.: Teratology 41:463-472, '90). As the first step of investigating possible mechanisms, we have examined the light microscopic morphology of RA-induced cardiovascular defects in chick embryos. Fertilized eggs were injected via yolk sac with 150 micrograms 13cisRA in dimethylsulfoxide (DMSO), DMSO or mock injection on embryonic day 5 (E5). On E6, E7, or E8, surviving embryos were sacrificed and fixed in 10% formalin. Thoracic blocks were exised, embedded in paraffin and serially sectioned through the heart, base to apex. Slides were stained, screened for tissue orientation, then coded and evaluated without knowledge of treatment group. Examination of serial sections permitted qualitative evaluation of conotruncal ridge volume, mesenchymal organization, necrosis and extent of fusion. Extent of fusion was the only parameter influenced by 13cisRA treatment. On E6, ridge fusion was incomplete in all groups at comparable levels. On E7, ridge fusion in 13cisRA-treated embryos had not progressed as far proximally as in controls. By E8, there was a significant difference in the extent of fusion between 13cisRA-treated and non-RA treated groups. We conclude 13cisRA-induced VSDs resulted from defective conotruncal ridge fusion and that the fusion defects did not result from decreased tissue volume, altered mesenchymal organization or increased necrosis. PMID- 1290154 TI - Abnormalities in ureter and kidney development in mice given acetazolamide amiloride or dimethadione (DMO) during embryogenesis. AB - These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown. PMID- 1290155 TI - Clinical anophthalmia: an epidemiological study in northeast Italy based on 368,256 consecutive births. AB - We describe an epidemiological and clinical study of Clinical Anophthalmia in a population of consecutive live and stillborns enrolled in a hospital based registry of congenital malformations in Northeast Italy during the period from 1981 to 1989; 22 cases were detected among 368,256 births yielding a birth prevalence of 0.60 per 10,000 (95% CI 0.34-0.84); 20 cases were associated with at least one other major malformation. Malformation syndrome, association, or sequence was diagnosed in 13, while a non-recognizable multiple defect pattern was observed in 7/20 (35%). A chromosomal anomaly was present in eight syndromic cases. No significant trend over time, nor space or time clusters, were detected. As most CAn cases are associated with other anomalies recognizable by ultrasound, a decreasing trend in its prevalence at birth is expected in the future. PMID- 1290156 TI - A population-based study of congenital diaphragmatic hernia. AB - From 1983 through 1987, in a California population of 718,208 births, 237 infants were born with a congenital diaphragmatic hernia (CDH), a birth prevalence of 3.30 per 10,000 total births (live births and stillbirths). We proposed that the various types of this defect, characterized by their different pathogeneses, would be reflected in differences in their descriptive epidemiologies. We evaluated various demographic, maternal, and infant characteristics for three major types of defects, the Morgagni hernia, the pars sternalis hernia, and the posterolateral hernia, categorizing the latter type into isolated defect (N = 129), multiple congenital anomalies including nonchromosomal syndromes (N = 86), trisomies (N = 10), and chromosomal anomalies other than trisomies (N = 2). For the posterolateral hernia, we present the distribution of associated anomalies (43%) and specifically of midline defects (19%). Although the number of cases for the Morgagni hernia (N = 5) and the pars sternalis hernia (N = 5) were small, comparisons with the posterolateral hernia suggested lower sex ratios, of borderline significance for the pars sternalis hernia (P < 0.09), and higher mean maternal ages for both groups. Within the posterolateral type, we found a significantly higher male to female ratio (M/F = 1.58) only for the isolated subgroup compared to the population (P < 0.03), and a borderline significant rural/urban difference in prevalences (2.12 vs. 1.45 per 10,000) (P < 0.06). Additionally, the distribution of monthly prevalence rates adjusted for gestational age suggested opposite seasonal trends between the isolated and the other posterolateral hernias; within this latter subgroup the difference between the highest monthly rate (1.68) and the lowest (0.96) was of borderline significance (P < 0.09). Our results suggest the need to consider the respective types and subgroups of CDH separately in epidemiologic studies. PMID- 1290157 TI - The perception of teratogenic risk of cocaine. AB - While there has been a substantial increase in recreational use of cocaine by young adults, conclusive evidence for cocaine teratogenicity in humans is lacking, and even those believing the drug is teratogenic agree that the rates are quite small. While counseling pregnant women on their teratogenic risk, it was our impression that there is an unrealistically high perception of reproductive risk of cocaine. We wished to quantify the perception of teratogenic risk of cocaine by the public, physicians, and by pregnant women who were counseled following gestational exposure to the drug. Women taking cocaine during the first trimester of pregnancy (n = 54), controls with post secondary education (n = 30), and physicians (n = 30) were asked, using a visual analogue scale, to quantify the teratogenic risk of cocaine and the tendency to terminate/continue the pregnancy after first trimester exposure; in the case of the "public" and physicians this was a hypothetical question. Both physicians and the controls perceived cocaine to be teratogenic (13.4 +/- 11% risk of major malformations by physicians, and 56.5 +/- 22.8% by the "public"). The controls believed cocaine to be as hazardous as thalidomide (57.2 +/- 25.6% risk for thalidomide). Asked whether they would wish to terminate such pregnancy in their family, most physicians (56%) and the controls (70%) had a greater than 50% tendency to terminate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290158 TI - Process of building biologically based dose-response models for developmental defects. AB - The problem of developing biologically-based dose-response models is addressed for predicting the prevalence of birth defects at low doses of toxic chemicals administered during pregnancy. To illustrate the process of incorporating biological information, a model is postulated to predict the prevalence of cleft palate for a chemical that reduces embryonic/fetal growth, which results in inadequate palatal cells for closure. Experimental bioassay data examining the prevalence of cleft palate in mice exposed to the herbicide 2,4,5-T are used to illustrate the process. With the limited data available, it is necessary to assume a model for cell growth and the relationship between the cell growth rate parameter and dose of 2,4,5-T. Also, a relationship between cleft palate prevalence and growth is assumed and then checked with experimental data. The purpose of the paper is not to provide a universal biologically based dose response model for cleft palate, but rather to demonstrate the extent, and type of information and data required. It remains to be seen if the form of the model is appropriate for chemicals that primarily produce embryo/fetal malformations or death via reduced or delayed cellular growth. PMID- 1290159 TI - Lens and mesenchyme ultrastructure in gestational day 11 trisomy 1 mice. AB - The lenses and head mesenchyme of two 11-gestational day trisomy 1 mouse embryos and a normal littermate were examined using transmission electron microscopy (TEM). One trisomic embryo had a small lens with a lens stalk; the other was aphakic. The resolution available with TEM allowed detailed evaluation of cell organelles, spatial relationships and the intra- and extracellular structural environment of the lens and head mesenchyme in normal and aneuploid embryos. Differences in fine structure between normal and trisomic lenses included (1) type of epithelium, (2) size of intercellular lacunae, and (3) activity of Golgi complexes. Differences in mesenchyme included (1) the number and size of cytoplasmic extensions, (2) shape of the cells, and (3) reduced endotheliomesenchymal interactions. PMID- 1290160 TI - Neural tube defects without neural crest defects in splotch mice. AB - Homozygous Splotch mutant mice (Sp/Sp) die on day 14 of gestation with neural tube defects, curly tail, and malformations of neural crest derivatives. Sp1H mice, which have a radiation-induced allele of Splotch with a similar phenotype, were used for this study. The neural tube defects are always located in the lumbosacral region and in 50% of the cases also in the region of the hindbrain. In this report, rare cases of neural tube defects and tail defects among the offspring of crosses between Splotch (Sp1H) heterozygotes are presented, which are not associated with a neural crest defect. This suggests that the development of the neural tube and neural crest defects in this mutant is caused by independent mechanisms or is dependent on the dosage of the mutant gene, with different thresholds being pathogenetic in the neural tube and neural crest, respectively. PMID- 1290161 TI - Craniometric measurements of craniofacial malformations in the X-linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H. AB - This study reports data on craniometric measurements in the X-linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H. Heads of normal females "+/+," normal males "+/Y," heterozygous mutant females "Hyp/+," and hemizygous mutant males "Hyp/Y" for each genetic background were examined. Data were collected via skull measurements. On a C57BL/6J background, the neurocranium of mutants "Hyp/+" and "Hyp/Y" was shorter and slightly higher than in normal counterparts. On a B6C3H background, mutant mice "Hyp/+" and "Hyp/Y" were shorter in neurocranial length than in normal counterparts. Viscerocranial height was larger in "Hyp/Y" than in normal counterparts. No differences in neurocranial and mandibular height were found. Mutant mice on a C57BL/6J background were compared to mutant mice on a B6C3H background. No differences in neurocranial length were found. Cranial length was shorter in "Hyp/Y" on C57BL/6J than in "Hyp/+" on B6C3H. Facial length parameters were shorter in "Hyp/Y" on C57BL/6J than in "Hyp/Y" and "Hyp/+" mutant mice on B6C3H. Mandibular length was shorter in "Hyp/Y" on C57BL/6J than in "Hyp/+" on C57BL/6J and both mutant mice ("Hyp/Y" and "Hyp/+") on a B6C3H background. The results of this study indicate that craniofacial growth is less affected in mutant mice on a B6C3H genetic background than in mutant mice on a C57BL/6J genetic background. PMID- 1290162 TI - Preferred use of primary radiolabeled anti-platelet monoclonal antibodies. Comparison of immunoblotting methods for the analysis of functional domains on human platelets. AB - Several methodologies used for the identification and characterization of platelet receptors for antiplatelet monoclonal antibodies are compared. Two antiplatelet monoclonal antibodies, are investigated due to their potent effects on human platelet function. A platelet-activating monoclonal antibody, called M.Ab.F11, is able to induce platelet aggregation and granular secretion. A platelet-inhibitory monoclonal antibody, named G10, strongly blocks the platelet aggregation and granular secretion induced by M.Ab.F11, as well as by physiological agonists. In order to identify the specific antigens recognized by these monoclonal antibodies, we tested a number of immunostaining methods. Comparison of various procedures revealed that a high degree of nonspecific interactions with platelet proteins occurred when the commonly used secondary reagents, protein A and radiolabeled or enzyme-conjugated secondary antibodies interacted with the platelet proteins either in the presence or absence of primary monoclonal antibodies. On the other hand, we observed a high degree of specificity and selectivity when only radiolabeled anti-platelet monoclonal antibodies were used as single reagents. It is established that M.Ab.F11 interacts with the platelet membrane proteins of 32 and 35 Kd, and M.Ab.G10 recognizes 100 Kd protein, which corresponds to GPIIIa molecule. PMID- 1290163 TI - Collagen-induced rat platelet reactivity is enhanced in whole blood in both the presence and absence of dense granule secretion. AB - Collagen induced aggregation, ATP secretion and thromboxane (TxB2) generation of storage pool deficient platelets were compared to normal platelets of closely related rat strains. Platelet function was monitored in citrated-platelet-rich plasma (PRP) and citrated whole blood. Wistar (W) and fawn-hooded (FH) rat strains and their F2 hybrids were utilized. The W strain, which is ancestral to the FH strain, is not storage pool deficient while the FH strain is. This was manifested by the total lack of collagen induced ATP secretion from platelets of the FH strain while the platelets of the W strain secreted normally. Utilizing platelets from the F2 generation of WxFH matings, the absence of dense granule secretion (ATP) from the FH platelets, as well as other platelet defects of FH rats, were shown to be associated with homozygosity for the red-eyed dilution gene [r]. The non-secreting FH platelets were utilized to determine the effects of secreted dense granule constituents upon collagen induced aggregation and TxB2 generation. The non-secreting storage pool deficient platelets did aggregate and did generate TxB2 upon stimulation with collagen; however, the storage pool deficient FH platelets demonstrated less TxB2 generation and did not aggregate as effectively as the normally secreting platelets of the W strain. When evaluating collagen induced platelet function in whole blood as compared to PRP, the storage pool deficient platelets remained less reactive than normally secreting platelets, but both platelet types demonstrated enhanced aggregation and increased TxB2 generation in whole blood. PMID- 1290164 TI - Thrombosis in spinal cord injury. AB - Some traditional coagulation assays and several new molecular markers of hemostatic activation were measured in 37 patients with spinal cord injury (SCI). Twenty one of the patients (57%) developed deep vein thrombosis (DVT). The radiofibrinogen uptake test (RFUT) was used to diagnose DVT. Thirty eight percent of quadriplegic and 88% of paraplegic patients developed DVT (p < 0.005). No significant differences were found in platelet counts, mean platelet volumes, fibrinogen levels, von Willebrand factor (Ag) levels, platelet factor 4 and beta thromboglobulin concentrations between the groups with and without DVT. Fibrinopeptide A, thrombin/antithrombin III (TAT) complexes and plasma D-dimer levels were significantly higher in the patients with thrombosis. Most patients with DVT had elevated TAT complex levels up to three days before the RFUT became positive. D-dimer levels were highest after the diagnosis had been made. PMID- 1290165 TI - Bacterial expression, purification, and partial characterization of amino acids 94-155 of human tissue factor pathway inhibitor (TFPI) as an inhibitor of blood coagulation factor Xa. AB - Tissue factor pathway inhibitor (TFPI) is a plasma-derived protein which inhibits two of the active serine proteases present during normal blood coagulation. Inhibition of both of these proteases, factors VIIa and Xa, is thought to require a factor Xa-TFPI complex. To begin to investigate the interactions between factor Xa and TFPI, amino acids 94-155, which encode for the second Kunitz domain (K2) of TFPI, were expressed, purified, and partially characterized. Expression of the recombinant peptide was accomplished using an E. coli expression system which produced the peptide at an expression level of approximately 2-5% of total cell protein. The peptide was localized to disulfide-linked refractile bodies which were solubilized by reduction in the presence of denaturant and the soluble protein refolded. Oxidized K2 was purified from the refold mixture using a two step procedure employing gel filtration chromatography and reverse-phase HPLC. The unprocessed form of the recombinant peptide, Met-Ala-K2 (rMA-K2), was characterized. This peptide was purified to apparent homogeneity as determined by SDS-PAGE, quantitative amino acid, Edman degradation, and electrospray mass spectrometry analyses (> 95% pure). The product bound to factor Xa covalently coupled to a solid support in the presence of 2M sodium chloride demonstrating its affinity for this enzyme. Preincubation of rMA-K2 peptide with factor Xa neutralized, with 1.1:1 stoichiometry, the ability of factor Xa to hydrolyze a small chromogenic substrate. Additionally, rMA-K2 prolonged the time to clot formation in a plasma-based assay dependent on factor Xa concentration. Finally, this peptide mildly prolonged the prothrombin and modified prothrombin times of normal pooled plasma. Taken together this data demonstrates that this region of TFPI inhibits factor Xa activity and allows for further characterization of this enzyme-inhibitor complex. PMID- 1290166 TI - The effect of dietary n-3 fatty acids on in vivo platelet aggregation in the cerebral microcirculation. AB - Diets enriched in n-3 fish oil have been suggested to decrease coronary artery disease in part through their ability to decrease cyclooxygenase-dependent platelet aggregation. However little is known concerning the effect of n-3 fatty acids on in vivo platelet aggregation. The purpose of these experiments was to determine whether dietary n-3 fatty acids affect the rate at which platelet aggregation occurs in cerebral arterioles. Fish oil (200 mg eicosapentaenoic acid + 143 mg docosahexaenoic acid/kg), corn oil or water was given daily by gavage to mice (n = 30) for six weeks and then in vivo platelet aggregation was induced by the light plus dye method, which injuries the endothelium. Two additional groups of mice were acutely treated with saline or indomethacin (0.5 mg/kg, ip), with the latter serving as a positive control for therapeutic inhibition of platelet aggregation. Serum thromboxane B2 was analyzed by RIA. All fed groups gained weight equally. Serum thromboxane B2 was decreased by 40% in the fish oil group (p = 0.05 vs. corn oil, p = 0.07 vs. water). The mean (+/- SE) time to first aggregate in pial arterioles was 101 +/- 6, 91 +/- 6 and 101 +/- 9 seconds in the fish corn oil and water groups, respectively. Indomethacin significantly increased the time to first arteriolar aggregate by 35% (p < 0.002) and caused an 80% reduction in serum thromboxane. These studies show dietary fish oil produces a moderate reduction in serum TxB2 level and does not affect arteriolar platelet aggregation whereas indomethacin produces a drastic TxB2 reduction and significantly slows platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290167 TI - Intraplatelet von Willebrand factor and ABO blood group. AB - Levels of plasma Von Willebrand Factor (vWF) are known to be influenced by ABO Blood Group but such an influence on platelet vWF is not known. Forty-three healthy donors had blood drawn for measurement of plasma and platelet vWF, both antigenic (vWF:Ag) and functional (RCo). Twenty-six were Group O and seventeen were Group A. Groups did not differ in age, platelet count, hemoglobin, white cell counts, platelet rich plasma counts nor length of in vitro storage of samples prior to assay. Plasma levels of vWF:Ag and RCo was lower in Group O as expected. Platelet RCo was lower in Group O and such a trend was present for vWF:Ag. This influence of ABO Groups on platelet vWF was modest compared to that on plasma vWF. PMID- 1290169 TI - Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial. AB - Severe intraoperative bleeding is one of the main problems during liver transplantation. Acquired hemostatic defects, namely primary or secondary hyperfibrinolysis, are considered significant pathogenetic events. Antithrombin III (ATIII), the main physiological serine protease inhibitor, has a critical role in the regulation of hemostasis. 29 patients with post necrotic cirrhosis undergoing liver transplantation were randomized to receive or not ATIII replacement therapy before the induction of anaesthesia and thereafter throughout surgery. Activation of both coagulation and fibrinolysis (increase of thrombin antithrombin complexes, fibrin and fibrinogen degradation products) were demonstrated in both groups. Blood loss and transfusion requirements were not affected by ATIII administration. PMID- 1290168 TI - Dibucaine elicits platelet procoagulant activity in factor VIII and factor X activation by a mechanism involving a sulfhydryl-dependent enzyme. AB - Dibucaine, a potent inhibitor of platelet aggregation and platelet release, was found to enhance the ability of fresh gel-filtered or washed human platelets to support factor VIII activation and factor X activation. Dibucaine-treated platelets increased the peak of factor VIII clotting activity by 2-fold compared to activity with untreated platelets. Similarly platelets optimally stimulated by dibucaine (1.0-1.5 mM for 5 min at 37 degrees C) supported as much factor X activation by factors IXa and VIII (measured in a chromogenic assay) as platelets optimally stimulated by ionophore A23187 (15 microM). An assay of platelet calcium-dependent sulfhydryl proteases was devised and used to test the effect of various inhibitors on these platelet proteases. The membrane-permeable sulfhydryl inhibitor Thiolyte MB inhibited platelet calcium-dependent protease activity; whereas, membrane-impermeable Thiolyte MQ did not. Thiolyte MB also blocked the ability of dibucaine-stimulated platelets to support factor X activation. Incubation of fresh, gel-filtered platelets with calpain inhibitor II (N-Ac-L-L Normethioninal) completely inhibited the calcium-dependent sulfhydryl protease activity of these platelets but did not affect their ability to support factor X activation after subsequent incubation with dibucaine. These data support the interpretation that an intracellular SH-dependent enzyme, which may not be calpain, is involved in the expression of platelet procoagulant activity in dibucaine-treated platelets. PMID- 1290170 TI - Identification of one base deletion in exon IX of the protein C gene that causes a type I deficiency. PMID- 1290171 TI - Maternal and neonatal hemostatic correlation. PMID- 1290172 TI - Desmopressin and postoperative thromboembolism. PMID- 1290173 TI - Improvement of blood gas levels after calcium-heparin treatment in patients with chronic obstructive pulmonary disease. PMID- 1290174 TI - Absence of anticardiolipin antibody in non-treated and heat-inactivated normal human sera. PMID- 1290175 TI - Reflections on the future of pre- and post-graduate medical education in thoracic surgery. PMID- 1290176 TI - Extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure. AB - Extracorporeal membrane oxygenation (ECMO) has been a successful treatment (82% survival) in over 5000 neonates with severe respiratory failure (80% predicted mortality without ECMO). ECMO is prolonged extracorporeal cardiopulmonary bypass achieved by extrathoracic vascular cannulation using a modified heart-lung machine. ECMO is currently the treatment of choice for full-term newborns with severe respiratory failure. The report summarizes indications, resulting complications, and future applications of neonatal ECMO. PMID- 1290177 TI - Use of the greater omentum for treatment and prophylaxis of anastomotic and stump dehiscence in major airway surgery. AB - In 6 patients suffering from anastomotic dehiscence following bronchoplastic procedures of the central airways or from acute bronchial stump fistula following pneumonectomy, the therapeutic efficiency of omentopexy in the management of the fistula was investigated. In 5 other patients with an increased risk of anastomotic leakage after sleeve pneumonectomy or pneumonectomy with carinal resection the omentum was effectfully used to prevent such complication. 4 out of 5 evaluable patients had successful treatment of the anastomosis and stump fistula. Complications arising from the additional laparotomy were not observed. PMID- 1290178 TI - Perioperative antibiotic prophylaxis in general thoracic surgery. AB - A prospective study of the efficacy of ampicillin in combination with sulbactam, a beta-lactamase inhibitor, (A/S) in perioperative prophylaxis was performed. The study consisted of two independent parts performed at the same time. Part I included 60 patients with lobectomies and segmentectomies. Group A (A/S 1 x 3 g "single shot") was compared with group B (A/S 3 x 3 g). Superficial wound infections occurred in 3 patients of group A and in 2 patients of group B. There was no empyema. Bronchitis and pneumonia were found in 10 patients of group A and in 7 patients of group B. Part II examined 25 pneumonectomies receiving A/S 3 x 3 g for 3 days. Concentrations of ampicillin and sulbactam in serum and lung tissue were determined and showed adequate levels to cope with usual bacteria in lung surgery. There was one superficial wound infection, 2 cases of bronchitis, and 2 cases of pneumonia. PMID- 1290179 TI - The surgical treatment of spontaneous pneumothorax by video-thoracoscopy. AB - Since March 1991, 66 patients with spontaneous pneumothorax were treated thoracoscopically employing the principles of minimally invasive surgery. Of these cases, 14 involved a first occurrence, 18 had a pneumothorax longer than 7 days, and 34 were recurrences; causative lung disease was determined in 25 patients. The blebs and bullae were ligated with chromic catgut Roeder loop or resected with the Endo-GIA stapler. If pathological changes to the lung consistent with Vanderschueren's stage IV were found (n = 36), the treatment was extended to include a parietal pleurectomy. No complications requiring therapy were encountered, the average postoperative hospital stay was 3.2 days. During an average observation period of 10 months (1-27) the recurrence rate was 4.5%. Thoracoscopic therapy proved to be a simple and safe method for all forms of spontaneous pneumothorax. PMID- 1290180 TI - Valvotomy for isolated congenital aortic stenosis in children: prognostic factors for outcome. AB - Early and late results after surgery for isolated congenital valvar aortic stenosis were evaluated in a total of 86 children under 16 years of age (mean 7.4 years). Primary procedure was always conservative. There were 7/86 (8.1%) early deaths. All infants who died after the operation were younger than 4 months of age. Among the clinical variables tested by the univariate analysis only age and duration of cardiopulmonary bypass were significant prognostic factors for early death. There were 6/67 (7.7%) valve-related late deaths. Multivariate analysis could not identify any risk factors for early and late mortality. Actuarial survival was 97% (95% CL 93-101%) after 5 years, 94% (88-100%) after 10 years, 90% (82-98%) after 15 years, and 87% (77-97%) after 20 years. A total of 22/79 (28%) early survivors had a first reoperation and 5 had a second reoperation. Long follow-up interval was the only significant factor for reoperation. Actuarial reoperation-free interval was 91% (85-98%) after 5 years, 70% (58-81%) after 10 years, and 50% (34-64%) after 15 years. Significant factors for poor valve function were long duration of follow-up, endocarditis, and young age at operation. The probability of normal valve function was 91% (84-98%) after 5 years, 67% (55-79%) after 10 years, and 54% (40-68%) after 15 years. PMID- 1290181 TI - Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation--a comparative clinical study. AB - In a prospective randomized study with 80 male patients scheduled for aorto coronary bypass grafting we investigated the influence of pulsatile and nonpulsatile perfusion mode on cell count (leukocytes, platelets, hematocrit), concentrations of thromboxane (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), plasma hemoglobin, PMN-elastase, complement C3a, clotting factor XII, lactate, plasmatic inhibitors (C1-INH, AT-III, alpha 2-antiplasmin), arterio venous oxygen difference (AVDO2) and hemodynamic parameters. Changes in hematocrit were similar in both groups, whereas plasma hemoglobin concentration was significantly higher with pulsatile perfusion. Platelet count paralleled changes in hematocrit and was not influenced by the perfusion mode. Leukocyte count as well as concentrations of PMN-elastase and C3a showed a strong increase during cardiopulmonary bypass, but there were no significant differences between the two groups. Similar changes of the concentrations of TXB2 and 6-keto-PGF1 alpha were noted irrespective of the perfusion mode applied. The observed alterations in the concentrations of clotting factor XII, alpha 2-antiplasmin, AT III and C1-INH largely paralleled hematocrit changes in either flow mode. Significant differences between the two groups were found with lactate: with nonpulsatile perfusion there was a slight but continuous increase, while with pulsatile flow lactate levels remained unchanged. There was no evidence for a better oxygen uptake (AVDO2) with pulsatile perfusion. Pulsatile perfusion seems to be advantageous to tissue perfusion, however, at the cost of a higher rate of hemolysis. We cannot confirm further salutary effects of the pulsatile perfusion mode with the 1-pump-system on cellular and humoral blood constituents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290182 TI - Experimental and first clinical experiences with implantable ultrasonic Doppler probes for postoperative bypass control after coronary surgery. AB - Concerning postoperative bypass hemodynamics after open heart surgery only few data are known. With this new implantable doppler probe we developed an easy-to use bedside method for monitoring postoperative bypass function after coronary artery bypass grafting. The accuracy of our method is shown by using a circulation model and by animal studies. Furthermore first clinical data are shown which support our conclusion of having found a sensitive method for monitoring small vessels' hemodynamics. PMID- 1290183 TI - The use of mesh-tube-constricted dilated or varicose veins as arterial bypass conduit. AB - In general, dilated and varicose veins are not used as arterial bypass grafts despite their physiological endothelial lining. A uniform small diameter may be achieved by inserting such veins into mesh tubes. To test the degree to which dilated veins can be constricted without forming folds, in-vitro and experimental investigations were performed before such composites were used for clinical reconstructive surgery. Ovine jugular veins with a diameter of 15 mm were inserted into 6 mm tubes. After casting in paraffin wax none of the specimens showed folds on the flow surface. In 12 sheep pairs of mesh-constricted jugular veins and native femoral veins were implanted as femoropopliteal bypass grafts. Six animals were killed at 6 months and 6 at one year. All bypasses remained patent and none showed signs of obstruction caused by folds or anastomotic hyperplasia at angiographic control. Intimal hyperplasia was significantly reduced from 416 +/- 143 microns in the midportion of native vein grafts to 231 +/- 76 microns (p = 0.0001 paired t-test) in constricted veins as well as at the anastomoses (358 +/- 256 microns vs. 180 +/- 73 microns; p = 0.008). Partially or totally mesh-tube-constricted varicose veins were used for infrainguinal reconstructions in 19 patients and for coronary revascularization in 3. All grafts showed an even calibration at control angiography. As constriction does not lead to internal folds, varicose or dilated veins may be used successfully as bypass grafts after insertion into mesh tubes. The external reinforcement reduces the intimal hyperplasia within the graft and also reduces anastomotic hyperplasia. PMID- 1290184 TI - Aortic valve replacement with the pulmonary autograft--experience of 23 cases. AB - Since 1988 an intensive homograft-program has existed at the Linz General Hospital. We have installed an own hospital-based homograft bank, where the allografts, after a 24-hour sterilization-period in an antibiotic solution and a controlled freezing procedure, are stored in liquid nitrogen at -196 degrees C. In 1991 for the first time aortic valve replacement was performed by pulmonary autograft in 23, mainly younger, patients. Essentially our technique conforms with that of D. N. Ross, in the course of which 18 autografts were implanted in subcoronary position and 5 aortic-root replacements were performed. 3 patients died perioperatively, 2 times a severe post-operative bleeding with following hypoxemic brain damage being the cause; 3 more patients had to be rethoracotomized because of postoperative bleedings. All these were attributed to a technical difficulty, which was overcome. In one patient a left-ventricular assist device had to be installed due to a left-ventricular failure, a successful heart transplantation followed on the 8th postoperative day. A follow-up was conducted in all patients every 3 months. In 2 patients a substantial valve incompetence of grade II-III and grade III was detected, all other patients showed no regurgitation of clinical relevance. Despite our initial difficulties it is our opinion that the many advantages-no anticoagulation necessary, no valve sound, less incidence of bacterial endocarditis, and longer durability-do justify this operative procedure. PMID- 1290185 TI - Isolated coronary artery bypass grafting in patients 75 years of age and older: is age per se a contraindication? AB - 137 patients with a mean age of 77.3 years (Group A) who underwent isolated coronary artery bypass grafting (CABG) were compared to 137 patients with a mean age of 55.6 years (Group B) who also underwent isolated CABG on the same or the adjacent day as the Group A patients. Group A patients were more commonly women, and had a significantly higher incidence of unstable angina, emergency operations, extensive coronary disease, peripheral vascular disease, and multiorgan debility. However, their left-ventricular function and the extent of revascularisation was similar to Group B patients. They also had significantly more operative mortality (7.2% vs 1.45%, p < 0.001). cardiac and non-cardiac complications, and longer hospital stay (14.2 vs 8.8 days, p < 0.001) than group B patients. At a mean follow-up of 29.8 months, no significant differences were noted in Group A versus Group B patients in terms of long-term survival (95% vs 94%), freedom from angina (82% vs 81%), cardiac readmission (10% vs 12%), or in the incidence of new myocardial infarction or new CABG. Actuarial survival at 4 years was 76.9% in Group A patients and 90.1% in Group B patients. Severe angina due to extensive coronary disease commonly makes urgent surgery unavoidable in this growing population of very old patients, but the operative mortality is modest and survivors do enjoy several years of life, remaining as free of angina, etc., as similar but younger patients. PMID- 1290186 TI - Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase III inhibitors feasible? A comparative study of amrinone and enoximone. AB - In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290187 TI - Congenital intrapericardial aneurysm of the left-atrial appendage. AB - An interesting case of congenital intrapericardial aneurysm of the left-atrial appendage is reported. The patient presented with recurrent supraventricular arrhythmias and progressive exercise intolerance and fatigue. Computerised axial tomography aided in the diagnosis by excluding the presence of any thrombus in the sac. The aneurysm could be safely excised via a left thoracotomy without cardiopulmonary bypass. The relevant literature on this problem is briefly discussed. PMID- 1290188 TI - [Design of a tibial intramedullary nail based on anatomic studies of intraosseous vessels]. AB - The design of the tibial medullary nail can be improved in order to preserve intraosseus vessels by osteosynthesis of the tibia. The nutrient artery of the human tibia enters the compacta in an average height of 33% dorsally and is leaving it in a height of 50% of the tibial length. In the medullary cavity the vessel splits up. The main branch continues the distal course on the dorsal/dorsolateral side of the medullary cavity (endosteal). In the distal diaphysis this endosteal vessel is of great importance, since the periosteal blood supply in this region with high incidence of pseudarthrosis is guaranteed only by branches of the anterior tibial artery. Using a new unreamed tibial nail, which is flattened dorsally, it is possible to preserve the endostal main artery of the tibia. PMID- 1290189 TI - [Morphometric analysis of the vascular tree of fetal tubular bones in an experimental model]. AB - The area of interest for the longitudinal growth is the distal growth plate. In a postmortem study we were interested in changes of the epiphyseal vascular length density after fracture and surgical therapy of foetal and neonatal femora (25th to 40th post conceptional weeks). We formed three groups of equal size. Group A (25 femora) was the control group. In group B and C we performed fractures in the middle third of the femora, in group C the femora was operated with a plate afterwards. A microangiography of all femora occurred and after plastination transparent slices were produced. In this manner we could study the epiphyseal vessels in the growth plate. Using image analyses we could show that vascular density of the epiphyseal growth plate could be verified only through fracture but not by surgical therapy. The integrity of the distal epiphyseal vascular architecture is the aim after all. PMID- 1290190 TI - [Evaluating the independence of paraplegic patients at the end of the first rehabilitation--a multicenter project of computer-assisted quality control in rehabilitation]. AB - Rehabilitation of patients who became handicapped due to illness or trauma is a difficult process, involving many therapeutic sections. The necessity to document the results of different rehabilitation programs led to the development of numerous scoring systems in the USA within the last 25 years, considering mainly functional results. The present functional assessment score (DMGP Selbstandigkeitserfassung fur Tetraplegiker) for the documentation of self sufficiency in tetraplegic patients after primary rehabilitation has been designed to record the quality of rehabilitation programs and has been exclusively designed for patients with quadriplegia, it there fore has the advantage of a better and more precise documentation over other general functional scoring systems, especially for the interests of different sections (occupational therapy, physiotherapy) being involved in this special rehabilitation program. The aim of the documentation is to record the degree of independence of tetraplegic patients after primary rehabilitation, considering the individual requirements of aids and the assumption of circumstances suitable for wheel-chairs. Since all data are collected on a computer-readable form each participating clinic has the opportunity for an individual analysis of the own results, as well as the opportunity of comparing it with the collective results. PMID- 1290191 TI - [Complications after surgical management of radial head fractures]. AB - As surgical management of fractures of the head of the radius unfortunately does not always yield satisfactory results, we performed a detailed study of these complications with special regard to several criteria. Over a period of five years, 44 cases of fractures of the head of the radius received surgical treatment at the Graz Hospital for Accident Surgery. Correlating with the literature known to us we found a relatively high rate of complications (17 of 44 cases, nine of the 17 cases required reoperation). If, however, we consider cases with a loss of mobility of up to 30 degrees in bending and stretching and rotation of the forearm still as satisfactory, of our 44 patients who were operated on for fractures of the head of the radius 37 showed satisfactory results and only seven poor ones. PMID- 1290192 TI - [Treatment of closed dislocations of the knee joint]. AB - Nineteen knee dislocations in 18 patients (one bilateral) occurred over a period of twelve years. The age range was 17 to 70 years with an average age of 33 years. There was no injury of the popliteal artery and five peroneal nerve injuries in the group. One compartment syndrome occurred after reduction. The follow-up study including examination showed good and satisfactory results for early surgical repair. After delayed surgical repair there were more signs of instability, pain and restrictive range of flexion movement. Early operative repair followed by cast bracing for six weeks and an intensive mobilisation therapy after cast bracing are the method of choice. An immobilisation period of three to four weeks is possible. PMID- 1290193 TI - [Local infections after replacement of the anterior cruciate ligament]. PMID- 1290196 TI - [(Model) continuing education regulation for the surgical specialty with emphasis on: vascular, thoracic, trauma and visceral surgery. In accordance with decisions of the 1992 95th German Medical Congress in Cologne]. PMID- 1290194 TI - [Cemented bipolar prosthesis in multimorbidity patients with coxarthrosis. Short- and intermediate-term results]. AB - The treatment of coxarthrosis with the cemented Duopleet prosthesis represents an efficient alternative to total hip prosthesis in elderly and polymorbid patients. The early results show a tolerable rate of complications. The patients can be mobilized early. The mortality seems to be low. Medium-term results are satisfactory. The rate of protrusions is lower than in patients with common femoral head prosthesis. Paraarticular ossifications are seen frequently. In numerous patients we found pain with projection to the operated hip. PMID- 1290195 TI - [Visualized three-dimensional reconstruction and image analysis in orthopedics and trauma surgery]. AB - Computer tomography is a commonly used technique for detecting pathological alterations in soft tissue and the skeleton. The remote access to image informations as well as the allocation of display and processing tools via networks enables improved diagnostic and therapeutic practice in orthopaedic and traumatologic surgery. The realization of a user friendly image analysis system displays and processes the acquired images in a modality oriented manner. Our method is based on a unique file format and specific evaluation procedures to produce the input data for three-dimensional display and algorithms for the individual design of implants. Our image analysis system can process the data of conventional computer tomographies with three or more mm distance. In contrast to the available systems there is a low significance of radiation effects. PMID- 1290197 TI - [Development of guidelines on the curriculum of continuing education in the area of surgery with emphasis on vascular, thoracic, trauma and visceral surgery. Continuing Education Commission of Surgical Specialty Societies]. PMID- 1290198 TI - Role of ultrasound in medical management of patients with renal stone disease. AB - Eighty-three patients with radiographically opaque renal stones were evaluated prospectively with ultrasound and compared to KUB (kidneys, ureters, bladder) with tomograms (KUB/T) to further define the use of ultrasound in the evaluation of renal calculi. The presence or absence and the size, number, and location of stones were analyzed and correlated for each modality. Ultrasound detected the presence of renal stones in 77 of 83 (93%) patients. However, all of the stones were detected on ultrasound in only 60% of these patients. Thirty percent (80 of 269) of the papillary-calyceal stones seen on KUB/T were missed on US; 66% of the stones missed measured 2 mm or less. Although ultrasound can be used for detection of intrarenal stones, KUB/T is a more accurate imaging examination for determination of size and number of small stones. PMID- 1290199 TI - Urolithiasis in a children's hospital: 1985-1990. AB - We performed a retrospective study of patients who had urinary tract stones and were seen at our hospital from 1985-1990. The study was intended to determine the prevalence of urolithiasis and optimal approaches to imaging. Clinical data and imaging studies of 87 patients were reviewed. The mean age was 15.7 years with a range of 3 months to 44 years. Fifty-four percent of patients were male. Most patients had a known predisposing cause for urolithiasis; patients with myelodysplasia and structural urologic problems predominated. Plain films were performed in 77 patients; 57% showed stones. Ultrasonograms were performed in 71 patients; 77% showed stones. Excretory urograms (EU) were performed in 49 patients; 84% showed either stones or their effect on the urinary tract. Computed tomographic (CT) scan was performed in 25 patients; all showed stones. PMID- 1290200 TI - Adult onset of renal angiomyolipoma in a patient with tuberous sclerosis. AB - The growth of renal angiomyolipomas in adult tuberous sclerosis patients has not been previously reported. We report one such case of the growth of an angiomyolipoma in a previously documented angiographically normal appearing kidney after the contralateral kidney was removed for angiomyolipoma 15 years earlier. PMID- 1290201 TI - Unusual renal oncocytomas: pathologic and CT correlations. AB - The unusual features of nine oncocytomas in five patients are reported herein. These include multiplicity in two, bilaterality in two, calcification in one, and association with renal cell carcinomas in three patients. Radiologists should be aware of these findings for this benign renal neoplasm. PMID- 1290202 TI - Lymphangioma presenting as a small renal mass during childhood. AB - Renal lymphangioma is a very rare lesion. A case of lymphangioma that presented as a small, hyperechoic renal mass on sonography in a child is reported. On CT, the lesion appeared as a low-density, enhancing renal mass. Despite its rarity, lymphangioma should be considered in the differential diagnosis of such a lesion. A suspected lymphangioma may be evaluated by percutaneous biopsy. PMID- 1290203 TI - Acute renal cortical necrosis: contrast-enhanced CT and pathologic correlation. AB - Acute renal cortical necrosis is a rare cause of acute renal failure that is usually associated with third trimester obstetrical complications. The appearance of this condition on contrast-enhanced computed tomography (CT) has rarely been described. A case of acute cortical renal necrosis is presented and the findings on contrast-enhanced CT are described. The pathologic correlation is also presented. PMID- 1290204 TI - Renal peripelvic lymphatic cysts (lymphangiomas) associated with generalized lymphangiomatosis. AB - Renal peripelvic lymphatic cysts (lymphangiomas) are usually seen as an isolated finding. They appear as multiple mass lesions with low attenuation on computed tomography (CT), and show no contrast enhancement. We present a case of renal peripelvic lymphatic cysts associated with generalized lymphangiomatosis, and examined with magnetic resonance imaging (MRI), CT, and lymphangiography. Multiplanar MRI demonstrated the extent of disease, including retroperitoneal lesions. The lesions had low-signal intensity on T1-weighted and high-signal intensity on T2-weighted images. The diagnosis of generalized lymphangiomatosis was verified by renal sinus cyst puncture, lymphangiography, and tissue biopsy. PMID- 1290205 TI - CT renal planimetry: effectiveness in the evaluation of individual renal function. AB - Computed tomographic (CT) renal planimetry was used to study individual renal function in 32 adult patients with urologic disease. CT results were well correlated to reference methods (r = 0.88, P < 0.001), which were radionuclide studies (N = 9) or separate creatinine clearance (N = 23). The difference between planimetric data and reference methods did not exceed 14% in any case and was less than 10% in 26 cases. PMID- 1290206 TI - Serial sonographic evaluation of "buckshot colic" following a penetrating gunshot wound. AB - This paper demonstrates the findings of various radiologic imaging modalities in a case of shotgun injury to the kidney. This case is unusual because buckshot entered the renal collecting system, and subsequently passed through the urinary tract in the urine, causing "bullet colic." References to such injury in the literature are discussed, along with role of each imaging modality in the initial and subsequent radiologic workup, with particular emphasis on the usefulness of ultrasonography in evaluation of this patient. PMID- 1290207 TI - CT of the urinary tract after abdominoperineal resection for rectal carcinoma. AB - Computed tomography (CT) after abdominoperineal (AP) resection for rectal carcinoma is a routine procedure for the detection of recurrent tumor and distal metastases. We reviewed sequential CT scans after AP resection in 52 patients in order to see whether the urinary tract as a neighboring organ is involved in recurrent malignancy. Bladder displacement in itself was not associated with hydronephrosis. Such hydronephrosis developed, however, in 14 patients--13 with a presacral mass, and one with retroperitoneal lymphadenopathy. In 23 of the 52 patients a presacral mass appeared, either fibrosis, infection, or recurrence. Severe hydronephrosis was found only with malignancy. We suggest that marked hydronephrosis associated with a presacral mass after AP resection is an indirect sign of malignancy. PMID- 1290208 TI - Non-Hodgkin lymphoma of the ureter: CT demonstration with pathologic correlation. AB - A case of a 42-year-old man with non-Hodgkin lymphoma of the ureter is reported. Diffuse lymphomatous infiltration of the ureter occurs rarely and is an uncommon cause of ureteral obstruction. Imaging-pathologic correlation is presented with CT images and autopsy specimens. PMID- 1290209 TI - Salpingoureteral fistula: CT appearance. AB - Laparoscopic laser surgery is becoming increasingly common as treatment for endometriosis. We report a case of computed tomographic (CT) demonstration of salpingoureteral fistula secondary to laparoscopic laser surgery. PMID- 1290210 TI - Congenital bladder diverticulum: an unusual presentation with abdominal mass, urinary retention, and renal failure in a young adult. AB - Computed tomographic (CT) evaluation of an abdominal mass diagnosed a huge 2-L congenital bladder diverticulum that caused urinary retention and ureteral compression leading to renal failure. The patient's renal failure resolved with decompression. His voiding dysfunction and retention resolved following diverticulectomy. PMID- 1290211 TI - Urinary bladder leiomyoma: magnetic resonance imaging findings. AB - Benign urinary bladder tumors are very rare, leiomyoma being the most common among them. We wish to report a case and discuss the radiological findings with special emphasis on magnetic resonance (MR) imaging. PMID- 1290212 TI - Uterine and bladder rupture during vaginal delivery in a patient with a prior cesarean section: case report. PMID- 1290213 TI - MR imaging in acute fracture of the penis. PMID- 1290214 TI - Fibrotic lesions of the testicle: sonographic patterns mimicking malignancy. AB - All testicular sonograms performed over a 2.5-year period were retrospectively reviewed, yielding eight patients with pathologically proven lesions consisting primarily of tubular sclerosis and interstitial fibrosis. Only two patients (25%) had a palpable abnormality. A variety of sonographic patterns was found, including focal hypoechoic or hyperechoic lesions and diffuse heterogeneity of the testicular parenchyma. The clinical and sonographic findings prompted open biopsy or orchiectomy in all cases. In the same time period, nine pathologically proven testicular malignancies were evaluated sonographically and displayed either well-defined hypoechoic or diffusely heterogeneous echo patterns. All but two of these patients (78%) had palpable abnormalities. This study demonstrates a significant overlap in the sonographic appearance of benign fibrotic lesions and testicular malignancies. When careful palpation of a sonographically heterogeneous or focal hypoechoic lesion fails to reveal a mass and serum tumor markers are negative, an open biopsy with frozen section analysis should be considered rather than proceeding directly to orchiectomy. Homogeneously hyperechoic masses can be considered benign and do not require surgery. PMID- 1290215 TI - CT of uterine cervical myeloma: case report. AB - Myelomatous involvement of the uterine cervix is rare and, to our knowledge, has not been reported previously in the radiologic literature. This report describes the computed tomographic (CT) findings and reviews differential diagnostic considerations. PMID- 1290216 TI - Metastatic transitional cell carcinoma simulating primary ovarian malignancy. AB - A case of metastatic transitional cell carcinoma (TCC) to the ovaries in a patient with prior grade I TCC of the bladder, which morphologically resembled a primary ovarian malignancy on computed tomography (CT), is described. Other tumors whose ovarian metastases can resemble primary ovarian tumors are also listed. PMID- 1290217 TI - Current usage of nonionic contrast. AB - All physicians who had billed Pennsylvania Blue Shield for at least three intravenous contrast studies during 1989 were surveyed on their use of nonionic versus ionic contrast. This surveyed group represents a diversity of hospital sizes, practice types, and group sizes. Of the 383 physician groups surveyed, responses were obtained from 285. The majority of the responding groups were radiologists (94.0%). Nonionic contrast is utilized in 41.3% of all intravenous studies. Radiologists use nonionic contrast in a much greater proportion than nonradiologists (P < 0.0001), with 17.6% of radiologists utilizing nonionic contrast in all of their patients. Conversely, 75% of nonradiologists utilize ionic contrast in all of their patients. For all physician groups surveyed, 40.3% utilize nonionic for at least 50%, while 27.6% use nonionics for more than 75% of their patients. The routine use of steroid premedication prior to the injection of ionic contrast is not a common practice. The increased utilization of nonionic contrast found in this survey may reflect the cross-section of physicians and practice types surveyed or may represent changing practice patterns among physicians utilizing contrast material. PMID- 1290218 TI - Update on interventional treatment of urinary obstruction. AB - During the last 20 years percutaneous nephrostomy has evolved as one of the basic procedures in the management of obstructive uropathy. This procedure is now widely available, it is relatively safe, and it offers rapid treatment of urinary obstruction regardless of underlying cause. Percutaneous nephrostomy is also the first step in a variety of antegrade ureteral procedures, including stent placement and ureteral dilation. PMID- 1290219 TI - [Influenza and congenital pathology]. PMID- 1290220 TI - [The immunoenzyme detection of the HIV-1 antigen by using monoclonal antibodies to protein p24]. AB - A test system using monoclonal antibodies to HIV p24 was developed for solid phase ELISA for detection of HIV antigen (AG) which helped detect the content of AG in samples with trace concentrations, less than 25 pg/ml. The test system can be used for AG monitoring in natural specimens (serum of HIV-infected patients and culture medium of infected cells) and for determination of antigen recombinant product of HIV gag gene. PMID- 1290222 TI - [The determination of the genotype of natural reassortant influenza A viruses according to the core protein genes by the methods of competitive dot hybridization and sequencing]. AB - Simultaneous circulation of different subtypes of influenza A viruses provides conditions for reassortant strains formation. A comparative investigation of genome of 47 influenza A virus strains (H1N1, H2N2, and H3N2) was carried out by competitive dot hybridization technique and sequence analysis of some of cDNA copies of the virus genes. All the genes of 43 strains encoding nonglycolysed proteins corresponded to the serum subtype of surface glycoproteins. The reassortant pattern of genome for some genes of core proteins was revealed in 4 viruses. All the dot hybridization data were completely confirmed by sequence analysis of the genes. PMID- 1290221 TI - [The anti-HIV activity of beta-glycyrrhizic acid]. AB - The anti-HIV activity of beta-glycyrrhizic acid (GA) and various derivatives was studied using various strains of HIV-1 and HIV-2 in primary infected lymphoblastoid cells MT-4 and monocyte cell line U-973 chronically infected with HIV-1 and containing provirus (GKV 4005). Beta-glycyrrhizic acid and its derivatives were shown to effectively inhibit HIV-1 reproduction in MT-4 cells. The antiviral effect of beta-GA sodium salt exceeded that of AZT in cells GKV 4005. The selective indices for some GA salts were evaluated, namely: 53 for 1NH4 salt of GA, 6.7 for 1K-2Li salt of GA; 4.45 for GA. The mechanism of GA action is discussed. PMID- 1290223 TI - [The effectiveness of lanthanide immunofluorescence and immunoenzyme analyses in differentiating viruses of the tick-borne encephalitis complex]. AB - Comparison of the efficacy of time-resolved fluoroimmunoassay (TR-FIA) and two variants of enzyme immunoassay: conventional (EIA-1) and one using biotin streptavidin system (EIA-2), in differentiation of viruses of the tick-borne encephalitis complex showed that, their specificity being similar, the TR-FIA method was 2-4 times as sensitive as EIA-2 and 8-32 times as sensitive as EIA-1. When the reactivity of the antigens was assessed by titers, the differentiating capacity was found to be similar and to depend upon the specificity of "sandwich" forming antibodies and the sensitivity of the immunoassay. When the reactivity of the antigens was assessed by relative reactivity in 4 test systems of different compositions, the differentiating capacity of TR-FIA was higher than that of EIA 1 and EIA-2 which allowed additional differentiation of 2 groups of viruses on the basis of qualitative characteristics of reactivity. PMID- 1290225 TI - [The geographical distribution of genetic variants of the tick-borne encephalitis virus]. AB - Geographic distribution of 185 tick-borne encephalitis (TBE) virus strains isolated in 8 physico-geographic areas and classified into six genetic variants was analysed. The strains of genetic variant I homologous to the Sophyin prototype strain were found to occur predominantly in the Far East and also frequently found in Western and North-Western parts of the East European plain. The vast territories from lake Baikal in the East to Ukraine in the West harbor mostly the strains significantly different from the Far-Eastern Sophyin strain. Hybridization experiments with oligonucleotide probes specific for the Neudorffle strain showed that the strains genetically similar to the virus of central European encephalitis occurred also in Eastern Europe and Western Siberia. It is concluded that a relationship exists between genetic types of TBE virus and their geographic origin. PMID- 1290226 TI - [A lyssavirus with an unusual antigenic structure isolated from a bat in southern Kyrgyzstan]. AB - Examination of 191 specimens of Chiroptera in Osh Province of Kyrgyzstan yielded 1 strain of lyssavirus from Myotis blythi, the isolate not belonging to serotype 1. The virus was designated Aravan by the area of its isolation. Its antigenic structure was studied using antinucleocapsid monoclonal antibodies of the Wistar Institute (Philadelphia, ISA) and Central Veterinary Laboratory of Great Britain (Waybridge, Great Britain). The paper presents its antigenic profile, brief characteristics of similarity and differences of the Aravan strain and known lyssavirus serotypes. PMID- 1290224 TI - [The specific reactivity of cDNA and deoxyoligonucleotide probes, complementary to the tick-borne encephalitis virus genome, with the RNA of strains of different geographical origins]. AB - Hybridization experiments with RNA of 143 tick-borne encephalitis (TBE) virus strains isolated in different parts of the distribution area were used to study the reactivity of kDNA- and a set of 10 synthetic deoxyoligonucleotide probes. The kDNA probe under certain conditions was shown to hybridize with RNA of all the strains under study, and under other (strict) hybridization conditions did so selectively with a small number of strains. The capacity of oligonucleotide probes for hybridization with RNA of TBE virus strains varied from 12% to 100%. The differences in the hybridization activity of kDNA- and oligonucleotide probes complementary to the genomes of the Sophyin strain (Far-Eastern subtype) and Neudorffle strain (Western subtype) with TBE virus strains were used for differentiation of the strains into six genetic variants. Comparison of the reactivity of molecular probes in experiments with RNA of TBE virus strains and viruses of the TBE complex showed that the differences of the strains belonging to different genetic variants from the prototype Sophyin strain were comparable to those of some members of the TBE complex, with the exception of Powassan virus. These data attest to the necessity of further studies dealing with specification of the taxonomy of TBE complex viruses. PMID- 1290227 TI - [The determination of measles antibody titers in the latex agglutination reaction]. AB - A new latex agglutination test (LAT) for detection of antibodies to measles virus in blood sera was developed. The latex diagnosticum consists of polymeric microspheres of national make carrying on their surface covalently bound measles virus antigen. The data on the specificity and sensitivity of the test are presented, and the results of titrations of blood sera from schoolchildren by traditional HI test and LAT are compared. LAT was shown to be highly sensitive, much simpler than the available methods for detection of measles antibodies and more economic, and therefore may be recommended for mass surveys. PMID- 1290228 TI - [The isolation of measles virus strains and the study of their hemagglutinating activity]. AB - Three measles strains Gag, Il, and Buk, were isolated from a suspension of mononuclear cells derived from measles patients in the active stage of the disease. Continuous Vero cell cultures were used for virus isolation. In the infected cell culture, all the isolates produced symplasts of different sizes and star-shaped or spindle-shaped multinuclear cells. The specificity of the cytopathic effect was proved by the adsorption of monkey erythrocytes on the surface of virus-affected cells. The isolates were identified in neutralization and HI tests with different immune preparations: measles gamma-globulin (national standard), hyperimmune rabbit sera to measles (Edmonston strain), rubella, and mumps viruses, S. sonnei and S. flexneri, as well as with sera from measles patients and subjects vaccinated with live measles vaccine L-16. The results of identification attest to isolation of 3 measles virus strains, one of which (Buk) possesses particularly high hemagglutinating activity. PMID- 1290229 TI - [The functional role of the glycosylation of viral components]. AB - An inhibitory analysis of the role of glycosylation and glycoproteins in the manifestations of the most important properties of African swine virus was carried out using a set of strains and variants with contrasting characteristics. Glycoproteins were shown to realize some virus functions such as virulence and its variability, intracellular transport and exocytosis of virions, hemadsorption, but not immunological recognition of the infected cells by cytotoxic T-lymphocytes. PMID- 1290230 TI - Focus on Caribbean journals the West Indian Medical Journal. PMID- 1290231 TI - Chlamydial infections in selected populations in Jamaica. AB - The importance of Chlamydia trachomatis as a cause of genital tract infection in Caribbean countries is largely unknown. Two hundred and sixteen cervical and urethral specimens were collected from patients with cervicitis and urethritis attending a Sexually Transmitted Diseases (STD) Clinic, a Gynaecology Clinic and a Family Planning Clinic in Kingston. Specimens were tested for chlamydiae by direct immunofluorescence and cell culture methods. They were also investigated for N. gonorrhoeae infections. Seventy-two of 138 patients (52.2%) at the STD Clinic were positive for chlamydiae; 28 of 50 (56.0%) from the Gynaecology Clinic and 11 of 28 (39.3%) from the Family Planning Clinic were positive. The prevalence of C. trachomatis (52.3%) was higher than that of N. gonorrhoeae (11.1%) in all groups. The results indicate that C. trachomatis is a common cause of genital tract infections in Jamaica. PMID- 1290232 TI - Hepatic ultrastructure in children with protein-energy malnutrition. AB - Samples of liver from eight children who died from malnutrition with its complications were studied by electron microscopy. Specimens were taken within one hour of death. These tissues had changes consistent with severe terminal illness, including mitochondrial swelling, with loss of matrix granules, disorganization of cristae, and evidence of calcium influx. Glycogen tended to be scanty. Lipid droplets were frequent. Endoplasmic membranes were depleted, and focal cytoplasmic degradation was frequent. Intracanalicular cholestasis was striking in four cases with loss of microvilli. Peroxisomes were depleted. This may be significant as peroxisomes are pivotal in the processing of very long chain fatty acids, in cholic acid metabolism and in elimination of free radicals. The observations were compared with previous reports in the literature, and with seven biopsies taken in 1970 from malnourished children who recovered. One, obtained on the fourth day, from a child with marasmus, showed atrophy of cellular organelles. The other samples were biopsied during the recovery phase, and displayed considerable restoration to normal morphology. Mitochondria had prominent matrix granules. Peroxisomes were frequently seen. There was no evidence of cholestasis. PMID- 1290233 TI - Unstable diabetic state produced by a small dose of streptozotocin in rats. AB - A diabetic state was induced with a single intraperitoneal dose (45 mg/kg) of streptozotocin in rats. Their fasting blood glucose concentrations oscillated between 12.7 +/- 1.9 mmol/l and 4.6 +/- 0.6 mmol/l during 35 days of monitoring. Their body weights were also reduced, while controls gained weight, although food consumption was not significantly different. Also, within the first 1/2-hour of the oral glucose tolerance test, blood glucose concentration increased in the diabetic and the control rats, but only in the control rats was there a simultaneous increase in serum IRI concentration (7.2 +/- 8 x 10(2) pmol/l to 27.0 +/- 5.2 x 10(2) pmol/l) which, like the blood glucose concentration, subsequently fell to fasting level in the control rats. In the diabetic rats, however, it was not until the following hour of the tolerance test that serum IRI concentration increased (3.4 +/- 0.3 x 10(2) pmol/l to 65.0 +/- 12.5 x 10(2) pmol/l) and blood glucose concentration began to fall. By the end of the test in the diabetic rats, blood glucose concentration fell but remained significantly higher than the control value. Additionally, no pancreatic tumours were identified in these diabetic rats. The results therefore suggest that an unstable diabetic state was produced by streptozotocin because the threshold for insulin secretion by glucose was increased, while the production of insulin by the pancreas was not significantly affected. PMID- 1290234 TI - Computed tomography of the calves. A screening procedure in the diagnosis of unilateral thrombosis of the deep veins of the lower limbs. AB - A prospective study of twelve patients, referred to the Department of Radiology of the University Hospital of the West Indies between March, 1990 and November, 1991 with a clinical diagnosis of deep vein thrombosis, was undertaken. All patients had computed tomography of the calves, as well as venography of the affected limb. Six patients (50%) had positive venograms. Of these, five had a difference of greater than 10% between the areas of the muscular compartments of the two limbs. Six patients had negative venograms but only three demonstrated a difference of a similar magnitude. The ratios of the area of the muscular compartment to the total limb area were also compared. Two of the six patients with positive venograms showed a greater ratio in the affected limb. One of the six patients with negative venograms showed a greater ratio in the affected limb. In this study, 83.3% of patients who did not have thrombosis of the deep veins of the calves had a ratio of muscular area to total limb area that was less than or equal to that of the unaffected side. This latter finding provides a potentially useful means of screening patients referred for venograms. PMID- 1290235 TI - Solitary rectal ulcer syndrome. AB - Solitary Rectal Ulcer Syndrome (Rectal Prolapse Syndrome) is an uncommon and imperfectly understood entity which, however, should be included in the differential diagnosis of ano-rectal symptoms. This article reports on the nine cases so far diagnosed at the University Hospital of the West Indies (UHWI), and offers a brief review of the condition. PMID- 1290236 TI - Arthroscopic surgery of the knee. AB - Seventy-nine arthroscopies of the knee were performed between January 1989 and March 1992. There were sixty-one males and eighteen females. The age range was from 12 to 78 years and the mean age was thirty-four years. Fifty patients had torn menisci. The menisci were removed arthroscopically in forty cases, arthrotomy being needed in the other ten cases. Following arthroscopic meniscectomies, patients returned to work in seven days, and to sporting activities in eight to ten weeks. Chondromalacia of the patella and femoral condyles were diagnosed in nineteen cases. These were treated by arthroscopic shaving and drilling of the irregular articular surfaces. In two cases, the procedure was used for assessment prior to other operations. Arthroscopy failed in two other patients due to pain and swelling and was normal in the remaining six cases. PMID- 1290237 TI - Shoulder dystocia: an obstetrical nightmare. AB - A nine-year review of 103 cases of shoulder dystocia identified obesity, diabetes mellitus and post-datism as important predisposing risk factors. There was a positive correlation with birthweight. Abnormal labour patterns were invariably absent and perinatal outcome was disastrous. The best strategy is to anticipate and avoid this obstetrical emergency. PMID- 1290238 TI - Diagnostic hysteroscopy. AB - Diagnostic hysteroscopy was performed on 100 patients. The most frequent indication was abnormal uterine bleeding. In premenopausal women, submucous fibroids were the main findings and in post-menopausal women, 59 per cent had an atrophic endometrium. Precise localization of the missing intrauterine contraceptive devices was achieved in all cases. Hysteroscopy improved diagnostic accuracy and reduced the need for blind curettage. PMID- 1290239 TI - Shared-induced paranoid disorder folie a deux between mother and son. AB - A case of shared-induced paranoid (psychotic) disorder (DSM III-R, 1987) between mother and son is presented. This disorder may be a more frequently occurring disorder than is generally recognised. It is suggested that more detailed family and social investigations be undertaken to unearth psychopathology in the social environment of the patient. In cases involving relatives, this may be another dimension to the genetic influence on mental illness. This is the first case reported in the West Indian medical literature. PMID- 1290240 TI - Retroperitoneal lipoblastoma. Report of a case and review of the literature. AB - We present the first case of retroperitoneal lipoblastoma at the University Hospital of the West Indies. This is one of the few reported cases in the general literature. PMID- 1290241 TI - Eosinophilic granuloma of the cervical and thoracic spine in a child. AB - A case of eosinophilic granuloma affecting a cervical vertebra, thoracic vertebra and pelvis in a child is reported. We present this case because multifocal eosinophilic granuloma lesions of the spine are rare and can present as this case did with both diagnostic and therapeutic problems. Preoperative diagnosis may be made by X-ray, isotope bone scan and needle biopsy, avoiding unnecessary surgical intervention. PMID- 1290242 TI - Very low calorie diets and pre-fasting prolonged QT interval. A hidden potential danger. AB - The association of torsade de pointes and a prolonged electrocardiographic QT interval is well described. A prolonged QT interval may be congenital or acquired in several ways--by the use of anti-arrhythmic agents exemplified by quinidine, by the presence of hypocalcaemia or hypokalaemia, by the use of psychotropic drugs, and by the presence of intrinsic cardiac disease or bradycardias. Possibly less well appreciated is the potential for drastic weight loss to prolong the QT interval, as the present case report illustrates. A young woman weighing 244 pounds lost 24 pounds in two weeks with a consequent prolongation of QTc interval from pre-diet value of 0.57 seconds to 0.72 seconds at admission, when severely symptomatic paroxysms of torsade de pointes were recorded. Successful therapy with lignocaine and prompt re-feeding suppressed the arrhythmia and, three days later, the QTc was reduced to almost its pre-diet state. A (UK) DHSS report offers guidelines in the use of very low calorie diets. This case suggests that a pre-diet electrocardiogram should be carefully assessed for QT prolongation before initiation of dieting to achieve serious weight loss. PMID- 1290243 TI - AIDS in CAREC member countries--a statistical update. PMID- 1290244 TI - [Circulating immune complexes and complement fragment iC3b in chronic polyarthritis during 12 months therapy with oral enzymes in comparison with oral gold]. AB - In the course of a double-blind randomized study lasting 1 year 19 patients suffering from ensured rheumatoid arthritis (ARA criteria) were treated with oral hydrolytic enzymes or oral gold salts. The effects of these therapies were examined in regard to changes in serum concentrations of circulating immune complexes (CIC) and the complement component iC3b. After 12 months treatment with oral enzymes we determined a therapeutically wanted significant decrease of CIC whereas CIC increased up to 6 months. The best but not significant result under therapy with oral gold salts concerning CIC was a decrease in 6 out of 9 patients after 9 months. The complement component iC3b diminished with either therapy during the first 6 months and increased afterwards. As well as the reduction of circulating immune complexes, the intensified inactivation of C3b into iC3b during the second half-year with both treatments indicates that there might be a slight improvement of the pathologically changed immunoreactions after 6 months only. Concerning the examined laboratory parameters, no significant difference was found between both therapies. PMID- 1290245 TI - [Comparison of results of daily blood pressure self-monitoring and general practice monitoring within the scope of a study assessing treatment of hypertension with quinapril]. AB - 24 hour blood pressure monitoring is a well established method in the field of antihypertensive research. Patients self recorded blood pressure values are an additional option to overcome the disadvantages of casual office readings- however they are not frequently used within intervention trials. To prove the usefulness of selfrecordings in clinical trials we investigated both selfrecordings taken twice a day and casual readings within intervals of 1 to 3 weeks, in this study on the efficacy and tolerability of the ACE-inhibitor Accupro. 108 hypertensive patients (grade WHO I to II) were included in this trial for ten weeks. Although blood pressures were measured by the patients using sphygmomanometers of the same type and the physicians, decisions to treat or to increase dosage were based on the patients' recordings only. Accupro was dispensed according to the package leaflet at a daily dosage of 5 mg up to 40 mg. In case of failing response to monotherapy, Accupro was combined with Diltiazem or with a diuretic. 7 patients discontinued the treatment due to mild adverse events, one did not cooperate. 82 of the remaining patients were treated effectively with Accupro monotherapy--60 (73%) got one dose daily, 22 (27%) 2 doses per day,--and in 18 patients a drug combination was required. Therapeutic response (RRd < or = 90 mm Hg) was gained within 86 of the 100 evaluable patients according to the doctors' and 83 according to the patients' records. In this respect the two methods used gave comparable overall results. This somewhat surprising fact is due to the design of the study, because treatment decisions were based on the selfrecordings only. Clinical trials based on selfrecordings are in some points preferable to casual office readings: As patients being normotensive at home should not be included into an interventional study, a change of dosage within this group is avoided. Additionally the compliance of a cooperative patient taking his blood pressure twice daily is at a high level. Measurements of each single patient may be evaluated statistically by time series analysis regarding longterm distribution of blood pressure-values. Taking the means of selfrecordings over adequate time-intervals eliminates the influence of "outliers" (occasionally extremely high or low values) and also reduces the standard deviation compared to that of the casual readings. Research work based on self recordings provides more information and therefore more security for treatment decisions. PMID- 1290246 TI - [Medically correct sitting, does it exist?]. AB - In the relaxed sitting position on conventional seats the lordosis of the lumbar spine is often lost. This can cause overstress of the discs, ligaments and muscles. Ergonomically correct seating aims at avoiding this. Some of the relevant seat characteristics concern back rest, seat base, arm rests, upholstering, individual adaptation and integration into the environment. In addition to office seats, "alternative" seats, car seats, and school benches are discussed. Since sitting invariably is associated with unfavourable statics, "correct" seating is a contradiction in itself. The aim can only be to minimize injury and to define a seat which causes the least damage. Considering its potential importance, the further neglect of this subject by medical research is unjustified. PMID- 1290247 TI - [Placebo forte: a contribution to the demystification of a therapeutic principle]. PMID- 1290248 TI - Progress in burn care--introduction. PMID- 1290249 TI - Burn depth: a review. AB - Despite the plethora of technologic advances, the most common technique for diagnosing burn depth remains the clinical assessment of an experienced burn surgeon. It is clear that this assessment is accurate for very deep and very shallow burns. But since clinical judgment is not precise in telling whether a dermal burn will heal in 3 weeks, efforts to develop a burn depth indicator are certainly warranted to accurately determine which dermal burns to excise and graft. This review summarizes the considerable literature in which a variety of techniques to determine burn depth have been used. PMID- 1290250 TI - Pre-operative radiotherapy as adjuvant treatment in rectal cancer. AB - From January, 1975 to December, 1987, 241 patients with rectal cancer underwent pre-operative irradiation and surgical resection. The radiation was delivered with 25 MeV photons, 5 days per week by 2.4 grays fractions up to a total dose of 36 grays. Surgery was curative in 195 patients; 57% had abdomino-perineal resection. Irradiation had to be discontinued in 3 patients and 4 patients subsequently developed severe acute ileitis. Postoperative mortality rate was 2.9%. The most frequent postoperative complications were delayed healing of abdominal wounds (18%) and perineal wounds (14%). Severe late complications occurred in 27 (13%) patients. The incidence of intestinal obstruction was 5%. Follow-up survivors ranged from 18 months to 13 years. Local failure occurred in 24 (12%) of the 195 patients. Local failure rates were 10% for Dukes' A tumors, 11.6% for Dukes' B, and 22.7% for Dukes' C tumors. Five and 10 year actuarial survival rates after curative surgery were 70% and 52%. The Dukes' classification was the only factor that influenced survival. PMID- 1290251 TI - Evaluation of the laparoscopic cholecystectomy on patients with simple and complicated cholecystolithiasis. AB - Laparoscopic cholecystectomy is now a well described method for the treatment of cholelithiasis. The purpose of this paper is to define its implementation, limits, risks and indications. Following a prospective method, the results of this treatment were compared in 187 patients with simple cholelithiasis and 75 patients with complicated cholelithiasis. Cholecystectomy was performed with a straight optic introduced through the paraumbilical region, and coupled with video camera. Two, 3, or 4 other trocars were inserted and placed as required by anatomic conditions. In the group with simple cholelithiasis, laparoscopic cholecystectomy was performed in 99% of the patients while in the group with complicated cholelithiasis the procedure was achieved in 75% of the patients. Immediate laparotomy was done in 1% and 25% of cases respectively in both groups. No interventional mortality occurred. Postoperative complications have been acceptable (1.6% and 2.7%), with no late complications reported. Our study shows that laparoscopic cholecystectomy is feasible in the majority of cases of complicated cholelithiasis and that the main advantages of this method were retained. PMID- 1290253 TI - The surgical management of benign and malignant thyroid neoplasms in Marshall Islanders exposed to hydrogen bomb fallout. AB - On March 1, 1954, a serious fallout accident occurred during the United States atomic testing program at Bikini in the Trust Territory of the Pacific Islands. Following the detonation of a large thermonuclear device (known as Bravo) an unexpected shift in winds resulted in deposition of radioactive debris on several inhabited atolls in the Marshall Islands. During the early post-detonation period military, sea, and air surveys traced the hottest portion of the parabolic cloud as it drifted in an ever widening pattern of diminishing concentration eastward and southeast of Bikini. The center of the cloud passed North of the Rongelap Atoll, which was the nearest inhabited atoll. This report concerns the development of thyroid lesions, the special circumstances encountered during thyroid surgery, and the results of the surgical management of benign and malignant lesions that were subsequently encountered in this population. PMID- 1290252 TI - "Endemic" idiopathic portal hypertension: report on 32 patients with non cirrhotic portal fibrosis. AB - The clinical features, surgical management, and long term follow up of 32 patients from Iran with idiopathic portal hypertension are reported. Many features of the disease are similar to those reported from India and Japan. The unsuspected finding was a 46% history of marked pica of clay (geophagia) in a subset of 26 patients. In addition, 81% of our patients had a prolonged prothrombin time, despite otherwise normal to minimally abnormal liver function tests. Liver biopsies revealed intrahepatic periportal fibrosis with subintimal thickening of terminal branches, and in many specimens a striking peri-ductular fibrosis was seen in the adjacent bile ducts. The spleen was very large with a dilated artery (external diameter: 11 mm to 15 mm). Portal venous pressure (PVP) was measured intra-operatively before and after clamping the splenic artery (SA). Clamping the SA consistently caused a decreased in PVP which ranged from 2.0 to 18.2 cm water with the mean +/- SEM of 9.7 +/- 1.5 cm water (p < 0.001, paired t test). It was equivalent to 32.3 +/- 3.6% decrease in PVP. Fifteen selected patients (Group I) were managed with splenectomy with excellent short and long term results. The selection criteria for splenectomy included a decrease in PVP to < 24 cm of water after clamping the SA. Three patients from this group were re examined 10 to 12 years following splenectomy. Cirrhosis had not developed, but the minimal abnormalities in the liver function tests had persisted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290254 TI - Percutaneous drainage of pancreatic pseudocysts: a prospective study. AB - We classify pancreatic pseudocysts in 3 types: post-necrotic type I, related to acute pancreatitis; post-necrotic type II, related to an acute attack superimposed on chronic pancreatitis; and retention type III, due to chronic pancreatitis with ductal stricture. A prospective study on percutaneous catheter drainage of post-necrotic pseudocysts (type I and II) was undertaken from 1987 to 1990. Twenty-three pseudocysts in 21 patients were drained. Overall recurrence rate was 4%; 2 patients had fistulization of the catheter into bowel; no deaths occurred. The procedure was successful in all type I cysts; in type II cysts it was associated with prolonged drainage and increased risk of complications when cyst-duct communication was present. Percutaneous drainage has no role to play in type III retention cysts. Guidelines regarding indications for treatment and the techniques employed are described. PMID- 1290255 TI - Postoperative wound infections and surgical face masks: a controlled study. PMID- 1290256 TI - Cecal diverticulitis: a continuing diagnostic dilemma. PMID- 1290257 TI - Recurrent pyogenic cholangitis: current management: a word of caution. PMID- 1290258 TI - Surgical complications of typhoid fever: enteric perforation. PMID- 1290259 TI - Falls in hemoglobin saturation during ERCP and upper gastrointestinal endoscopy. PMID- 1290260 TI - Burn shock resuscitation. AB - The goal of fluid resuscitation in the burn patient is maintenance of vital organ function at the least immediate or delayed physiological cost. To optimize fluid resuscitation in severely burned patients, the amount of fluid should be just enough to maintain vital organ function without producing iatrogenic pathological changes. The composition of the resuscitation fluid in the first 24 hours postburn probably makes very little difference; however, it should be individualized to the particular patient. The utilization of the advantages of hypertonic, crystalloid, and colloid solutions at various times postburn will minimize the amount of edema formation. The rate of administration of resuscitation fluids should be that necessary to maintain satisfactory organ function, with maintenance of hourly urine outputs of 30 cc to 50 cc in adults and 1-2 cc/kg/% burn in children. When a child reaches 30 kg to 50 kg in weight, the urine output should be maintained at the adult level. With our current knowledge of the massive fluid shifts and vascular changes that occur, mortality related to burn-induced hypovolemia has decreased considerably. The failure rate for adequate initial volume restoration is less than 5% even for patients with burns of more than 85% of the total body surface area. These improved statistics, however, are derived from experience in burn centers, where there is substantial knowledge of the pathophysiology of burn injury. Inadequate volume replacement in major burns is, unfortunately, common when clinicians lack sufficient knowledge in this area. PMID- 1290261 TI - Pathogenesis of edema formation in burn injuries. AB - One of the obvious acute features of cutaneous thermal injury is the swelling of the involved tissue. This swelling is caused by a fluid shift from circulating plasma. Along with the evolution of intravenous fluid therapy in trauma and surgery, the implementation of such therapy to burn victims has improved survival. Edema generation aggravated by fluid therapy may, however, represent a source of increased morbidity. This paper presents a review of the literature on postburn edema generation, focusing mainly on fluid physiology. It is well documented that fluid is lost from the circulation into burned tissue because of a moderate increase in capillary permeability to fluid and macromolecules and a modest increase in hydrostatic pressure inside the perfusing microvessels. Recently it was discovered that a very negative interstitial pressure develops in thermally injured skin. This pressure constitutes a strong "suction" adding markedly to the edema generating effect of increased capillary permeability and pressure. PMID- 1290262 TI - Smoke inhalation: diagnosis and treatment. AB - Smoke inhalation, defined as airway or pulmonary parenchymal injury resulting from the inhalation of toxic combustion products, presents with a wide range of severity in patients with and without skin burns. In patients with severe injuries, the diagnosis is obvious on the basis of the history and clinical presentation; in patients with less severe injuries or those in whom the clinical consequences are delayed, diagnostic precision is difficult because diagnostic clues provide only indirect information. There is no specific treatment so diagnosis is not critical for patient management. Patients at risk include 20% to 30% of flame burn victims who should receive vigorous supportive care. The mortality rate of smoke inhalation victims without a burn is < 10%. With a burn the mortality rate is 30% to 50%, suggesting that thermal injury or its treatment is responsible for further lung damage. Endotracheal intubation provides definitive treatment for obstructed or soon-to-be obstructed patients. However the diagnosis of smoke inhalation per se is not an indication for airway intubation and respiratory support; 12% of patients without a burn require intubation versus 62% of those with a burn. A translaryngeal tube can be converted to a tracheotomy safely in burn victims; tracheotomies are easier to manage if burns of the neck are excised and grafted prior to placement. Mechanical ventilation with positive end expiratory pressure (PEEP) is the treatment for the pulmonary injury. The early lesions of smoke inhalation often progress in the context of sepsis and other complications of the burn illness to a clinical state consistent with adult respiratory distress syndrome. PMID- 1290263 TI - The role of mediators in the response to thermal injury. AB - Inflammatory mediators play a major role in both the local burn wound and the systemic response to burn injury. Oxidant and arachidonic acid metabolites are involved in the initial burn edema process. The mediators as well as the cytokines released from activated macrophages also result in an early generalized inflammatory response. The later postburn hyper-metabolism is initiated and perpetuated by these same mediators, especially the cytokines, tumor necrosis factor, interleukin-1, and interleukin-2. Circulating endotoxin from the wound or the gut also appears to be involved. The postburn septic response is now recognized to be the result of inflammation; infection is not necessary. Mediator induced priming of the inflammatory cells by the burn itself results in an exaggerated response to infection in the postburn period. Defining the specific mechanism of injury and mediators involved can result in a major improvement in burn care, especially since many mediator inhibitors are already available for clinical use. It is essential that the clinician understand this pharmacologic manipulation in order to be able to optimally utilize these future advances. PMID- 1290264 TI - Benefits and limitations of burn wound excision. AB - This review is intended to provide a balanced view of the role of surgical burn wound excision and closure within the larger context of the total care and rehabilitation of patients with burn injury. The historical background leading to present practice is outlined. The salient technical and logistical problems associated with the performance of wound excision are discussed, with emphasis on the necessity for expeditiously completing these procedures which are associated with major blood loss. A realistic analysis of the results of excisional therapy in patients with burns of varying severity is presented. Benefits attributable to the surgical phase of therapy become progressively more difficult to identify as the size of deep burns increases beyond 20% of total body surface area. PMID- 1290265 TI - Biologic wound coverings in burn treatment. AB - A review of biologic wound coverings currently in use is presented. These include homografts, xenografts, embryonic membranes, and tissue derivatives. The indications, advantages, and disadvantages of such materials are discussed. Finally, future research directions are suggested. PMID- 1290266 TI - Burn wound closure using permanent skin replacement materials. AB - Over the past decade, very significant advances in the development of clinically useful, permanent skin replacement materials have taken place. The most prominent and successful approaches to the physiological closure of an open wound have been either by creating a totally artificial dermal matrix material, by using culture techniques to expand cell populations for autologous transplantation, or by using a combination of these methods. As a result of substantial early progress in this field, permanent skin replacement materials as a treatment modality promise significant contributions to improved wound management and increased survival rates for patients with devastating soft tissue destruction such as massive burn injuries. PMID- 1290267 TI - The immunologic response to thermal injury. AB - Thermal injury is associated with altered immune defense. Extensive and deep thermal injuries lead to depressed immune defense function with both cellular and humoral defense affected. There is an intricate interaction between various components of the immune system. The altered specific immune response is seen as a depressed ability to produce active rosette-forming cells. Depressed stimulation of lymphocyte proliferation as well as the mixed lymphocyte response have also been recorded following burns. These effects are modulated by the release of kinins, prostaglandins, anaphylatoxins, superoxides, and leukotrienes, all of which can influence the inflammatory response following thermal injury. The humoral immunity is altered as seen by decreased levels of immunoglobulins, activation of complement with release of anaphylatoxins, and formation of membrane attacking complexes leading to inflammation and cytolysis. The immune response to burns is also affected by factors other than this injury, such as nutrition or diseases such as diabetes mellitus or disorders of the lymphoproliferative type. The immune response is also influenced by some drugs used for other reasons such as steroids, chemotherapeutic agents, and topical agents used for burn wound care. The immune reaction to a burn is also influenced by the additive effect of superimposed infections. Removal of injured tissue without the need for extensive transfusion will improve the ability of the burned patients to use their immune defense system in a fruitful way. PMID- 1290268 TI - The changing epidemiology of infection in burn patients. AB - Topical chemotherapy, prompt excision, and timely closure of the burn wound have significantly reduced the occurrence of invasive burn wound infection and its related mortality. Since wound protection is imperfect and invasive wound infection may still occur in patients with massive burns in whom wound closure is delayed, scheduled wound surveillance and biopsy monitoring are necessary to assess the microbial status of the burn wound and identify wound infections caused by resistant bacteria or non-bacterial opportunists at a stage when therapeutic intervention can control the process. As a reflection of the systemic immunosuppressive effects of burn injury, infection remains the most common cause of morbidity and mortality even though the occurrence of wound infections has been significantly decreased. Pneumonia is the most frequent infection occurring in burn patients today but the improvements in patient management, wound care, and infection control have made bronchopneumonia the most common form of this infection and gram-positive organisms the most common causative agents. The organisms causing bacteremia that exert a species specific effect on the mortality related to extent of burn injury and patient age have changed in concert with changes in wound flora. Infection control procedures, including scheduled surveillance cultures, utilization of cohort patient care methodology, strict enforcement of patient and staff hygiene, and patient monitoring have been effective in eliminating endemic resistant microbial strains, preventing the establishment of newly introduced resistant organisms, diagnosing infection in a timely fashion, instituting antibiotic and other necessary therapy in a prompt manner, and documenting the effectiveness of present day burn patient care and the improved survival of burn patients. PMID- 1290270 TI - Nutritional support of the burned patient. AB - Burn patients develop a number of physiologic alterations among which is a markedly increased metabolic rate. Other metabolic changes include an increased rate of glucose production and utilization, a decreased rate of lipid metabolism, and an increased rate of both protein catabolism and anabolism. These alterations can effect other physiologic parameters, including immune function. They necessitate administration of large quantities of calories and protein to achieve positive nitrogen balance. The physiologic derangements leading to the hypermetabolism and the methods for supplying the nutritional needs are discussed in this review. PMID- 1290269 TI - The metabolic effects of thermal injury. AB - Major thermal injury is associated with extreme hypermetabolism and catabolism as the principal metabolic manifestations encountered following successful resuscitation from the shock phase of the burn injury. Substrate and hormonal measurements, indirect calorimetry, and nitrogen balance are biochemical metabolic parameters which are useful and more readily available biochemical parameters worthy of serial assessment for the metabolic management of burn patients. However, the application of stable isotopes with gas chromatography/mass spectroscopy and more recently, new immunoassays for growth factors and cytokines has increased our understanding of the metabolic manifestations of severe trauma. The metabolic response to injury in burn patients is biphasic wherein the initial ebb phase is followed by a hypermetabolic and catabolic flow phase of injury. The increased oxygen consumption/metabolic rate is in part fuelled by evaporative heat loss from wounds of trauma victims, but likely also by a direct central effect of inflammation upon the hypothalamus. Although carbohydrates in the form of glucose appear to be an important fuel source following injury, a maximum of 5-6 mg/kg/min only is beneficial. Burn patients have accelerated gluconeogenesis, glucose oxidation, and plasma clearance of glucose. Additionally, considerable futile cycling of carbohydrate intermediates occurs which includes anaerobic lactate metabolism and Cori cycle activity arising from wound metabolism of glucose and other substrates. Similarly, accelerated lipolysis and futile fatty acid cycling occurs following burn injury. However, recent evidence suggests that lipids in the diet of burned and other injured patients serve not only as an energy source, but also as an important immunomodulator of prostaglandin metabolism and other immune responses. Amino acid metabolism in burn patients is characterized by increased oxidation, urea synthesis, and protein breakdown which is prolonged and difficult to reduce with current nutritional therapy. However, the current goal of nutritional support is to optimize protein synthesis. Specific unique requirements may exist for supplemental glutamine and arginine following burn injury but further research is needed before enhanced branched chain amino acids supplements can be recommended for burn patients. Recent research investigations have revealed the importance of enteral feeding to enhance mucosal defense against gut bacteria and endotoxin. Similarly, research has demonstrated that many of the metabolic perturbations of burns and sepsis may be due, at least in part, to inflammatory cytokines. Investigation of their pathogenesis and mechanism of action both at a tissue and a cellular level offer important prospects for improved understanding and therapeutic control of the metabolic disorders of burn patients. PMID- 1290271 TI - Prevention and treatment of postburn scars and contracture. AB - The management of postburn reconstruction is complicated by the frequent occurrence of multiple reconstructive needs in a single patient. This article presents a simple, comprehensive approach to burn scar reconstruction. The primary aim of the surgeon is to prevent burn scar deformity by rapid wound closure, correction of tissue deficiencies, and assiduous attention to postoperative splinting and compression therapy. The initial step in managing secondary deformities is to prioritize reconstructive needs. Reconstruction is then carried out in a stepwise fashion aiming to restore active function first, followed by passive function, and finally addressing aesthetic reconstruction. Reconstructive techniques are applied in a hierarchy from simplest to most complex. Primary excision and closure of scars by reorientating the scar to the lines of relaxed skin tension can significantly improve appearance. The use of z plasty, flap repair, and tissue expansion are also reviewed. Skin expansion, in particular, has become the standard management of postburn alopecia and, although associated with a relatively high rate of complication, has significantly improved the aesthetic appearance of such patients. The management of common problems affecting the face is discussed with particular reference to management of the eyelids, oral commissure, and lips. These areas need to be reconstructed as aesthetic units and each requires individualized management of donor tissue. The reconstruction of the burn patient is often a long process requiring multiple procedures. The approach presented here advocates a stepwise, prioritized approach aiming at both maximum function as well as optimal appearance. PMID- 1290272 TI - Anti-Ro autoantibody with cross-reactive binding to the heavy chain of immunoglobulin G. AB - Autoantibodies directed at the intracellular Ro ribonucleoprotein complex are found in the serum of patients with systemic lupus erythematosus (SLE) and related autoimmune diseases. The antigenic stimulus for the induction of these autoantibodies is unknown, although we have previously demonstrated that the Ro protein and immunoglobulin G (IgG) share immunologic determinants bound by anti Ro antibodies. The present study further defines the fine specificity of this cross-reactive binding. Using both patient autoanti-Ro antibodies and antigen induced rabbit anti-Ro serum, the binding specificity for IgG was located to the heavy chains of IgG outside the Fc domain. F(ab')2 fragments of IgG were observed to inhibit specific Ro binding by either human or antigen-induced rabbit sera, while Fc fragments of IgG failed to inhibit Ro binding. Anti-Ro sera were found to bind the heavy chains of IgG in immunoblots, and the antibodies eluted from these heavy chains were capable of immunoprecipitating the Ro particle from human cell extracts. Not all patient sera with anti-Ro antibodies possessed IgG binding antibodies. Studies of cyanogen bromide digestion fragments of IgG implicate the hinge region of IgG as the region cross-reactive with the Ro protein. The nature of this cross-reactivity may be important in understanding the induction and/or perpetuation of the anti-Ro response in patients with autoimmune disease. PMID- 1290273 TI - The pre-travel medical evaluation: the traveler with chronic illness and the geriatric traveler. AB - The pre-travel medical evaluation of elderly patients and patients with chronic illness requires special assessment and advice. Screening and special precautions are reviewed for traveling patients with respiratory disease, cardiac disease, sinusitis, diabetes mellitus, HIV infection, and other chronic medical conditions. Current guidelines for empiric therapy and prophylaxis of travelers' diarrhea are reviewed, with emphasis on concerns in geriatric or chronically ill travelers. Special considerations such as potential drug-drug interactions and insurance coverage are also discussed. PMID- 1290274 TI - Malaria prophylaxis: taking aim at constantly moving targets. AB - The prevention of malaria infections is one of the most important functions that any clinician can perform for those traveling to tropical geographic regions where malaria risks are present. The prophylaxis question has become complicated by continued emergence of chloroquine-resistant strains of Plasmodium falciparum, the recent appearance of Plasmodium vivax resistance, and the availability of a wide choice of antimalarial pharmaceuticals. Chemoprophylaxis may produce different toxicities among various patient populations. With increasing numbers of women who travel during their professional lives, there are potential implications for using chemoprophylaxis during pregnancy. Children are unable to tolerate certain antimalarials because of toxicities unique for them. In some instances, the safest and most palatable formulations for children are not even available in the United States and must be purchased in Canada or elsewhere. Reliance upon chemoprophylaxis alone has proven to be increasingly futile. With the introduction of new repellent formulations and nontoxic insecticides for use on clothing or bed netting, there are non-pharmacologic adjunctive measures which can now be considered first-line for the prevention of malaria infections. PMID- 1290275 TI - Current prevention and management of acute mountain sickness. AB - Acute mountain sickness was known to the Chinese in ancient times, as they traversed mountain passes between the Great Headache and Little Headache mountains into present-day Afghanistan. The Jesuit priest, Father Joseph Acosta, lived in Peru during the sixteenth century; he described both this syndrome and deaths which occurred in the high Andes. The incidence of high-altitude illness will rise as previously remote sites become more accessible to trekkers and skiers. Prevention and treatment are important concerns for those physicians who wish to advise their more adventuresome patients properly. This article incorporates a selected review of pertinent investigations, in the English language literature over the past five years, into material previously presented at travel symposia for clinicians managing the prophylaxis and treatment of acute mountain sickness. PMID- 1290276 TI - Evaluation of the returned traveler. AB - Recognition of clinical syndromes in returned travelers is an important part of providing care to international travelers. The first step is to take a history with attention to pre-travel preventive measures, the patient's itinerary, and potential exposure to infectious agents. The patient should then be examined to document physical signs, such as fever, rash, or hepatosplenomegaly, and to have basic laboratory data obtained. This evaluation will provide most physicians with the necessary information to generate a differential diagnosis. Each diagnosis should be matched against the incubation period of the disease, the geographic location of illness, the frequency of illness in returned travelers, and the pre travel preventive measures. Careful attention to these aspects of patient care should result in the appropriate diagnosis and therapeutic intervention for the ill returned traveler. PMID- 1290277 TI - [Further experiences with ovum lavage with respect to preventing premature labor]. AB - Between January and December 1990, lavage of the ovum was performed in 64 gravidae with actual or potential symptoms of premature labour. Subsequently the lavage fluid was microbiologically examined. The present study discusses the indications for this new method, how it is performed and the results obtained. Microorganisms possibly necessitating treatment were detected in the lavage fluid of 30 (47%) of the gravidae at risk. Thirty-nine patients manifested actual symptoms of imminent premature birth, such as labour or critical cervical status. Results of fluid tests were positive in 23 (59%) of these patients, while according to the results of conventional cervical or vaginal smear tests performed simultaneously, treatment was necessary in only 13% of them. The majority of the microorganisms in the lavage fluid (coagulase-negative, haemolytic and group D streptococci were usually detected) are only facultatively pathogenic and are found in small quantities in cervical smears as normal "local flora". The mean delivery date was in gestational week (GW) 37/1, and for patients with antibiosis produced by a suitable antibiotic in GW 38/3 (10 weeks after lavage was performed). In view of the results of this study, bacteriological testing of ovum lavage fluid may be regarded as a useful complementary method for detecting ascending infections. It may advance pathogenetic research into late abortion and premature birth and further reduce the premature birth rate. PMID- 1290278 TI - [Uses of vaginal pH measurement for prevention of premature labor. Results of a prospective study]. AB - The influence of the microflora of the vagina and cervix has been undervalued for the induction of premature birth. Examination of the microbiological problem by determination of the vaginal pH in combination with the microflora (Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum). Report of the outcome of 161 prospective, ad the beginning normal pregnancies in comparison of 200 primary hospitalized pregnancies with symptoms of imminent premature birth. CONCLUSION: The vaginal pH is a very useful parameter of screening for identification of disturbances of the microflora in practice. In cases of pathologic pH (> 4.5) it is possible by therapy to reduce the premature birth rate. PMID- 1290279 TI - [Detection of rupture of fetal membranes using a commercially available fibronectin test kit]. AB - In a clinical examination an attempt was made to confirm the aptitude of a commercially available immunoassay to detect amniotic fluid. Pure amniotic fluid gained by amniocentesis, not mixed with other secretions, was used. On examination using three different batches the sensitivity of this test amounted to 35/55 in all, or 64%. We came to the conclusion that the present test was not sufficiently reliable to prove or disprove the discharge of amniotic fluid. An explanation is needed especially regarding the role played by the forces which occur during contractions and the presence of cervical and vaginal secretions when fetal fibronectin is found to be present. The evidence of fetal fibronectin could possibly become more important as a predictor of imminent labour than as being proof of the admixture of amniotic fluid in cervical and vaginal secretions. PMID- 1290280 TI - [Does the "fatty pelvis" exist? Quantitative computer tomography studies]. AB - 50 Patients weighing between 45 and 114 kg underwent standardized computed tomography of the pelvis. Fat compartments from inside and outside of the small pelvis were assessed quantitatively by means of tracing the fat tissue borders and planimetry. Fat compartments within the small pelvis showed a rather weak correlation with body weight and the so called Rohrer-Index as a weight/height Index, correlations with the latter being slightly better. From the fat compartments within the single levels the functional reduction of birth channel diameters caused by fat tissue was calculated for. The weight/height-index dependent increase of space demand within the birth channel was rather pronounced at the pelvic brim becoming slighter when reaching mid-pelvis or even pelvic outlet. Hence, the common assumption can no longer be maintained, that adiposity necessarily causes soft tissue dystokia due to larger fat compartments within the small pelvis. PMID- 1290281 TI - [Comparison of the rate of complications after primary, secondary and emergency Cesarean section]. AB - 3799 women delivered by cesarean section at the Department of Obstetrics and Gynaecology of the University of Ulm between 1978 and 1988 were retrospectively divided into three groups, according to the urgency of cesarean section: group [1]: elective cesarean section (n = 1333), group [2]: urgent cesarean section (n = 2295), group [3]: emergency cesarean section (n = 171). Group [1] comprised the greatest risk in terms of maternal diseases, pregnancy complications and previous cesarean sections, group [2] the least. Intraoperative complications were seen more often in group [3] than in groups [1] and [2] and included a greater number of operations lasting more than 2 hours (group [3]: 2.3%, group [1] and [2]: < or = 0.5%), a higher incidence of severe blood loss and consequent need for blood transfusions, and of serious complications such as damage to adjacent organs and need for hysterectomy (group [3] 4.7%, groups [1] and [2]: 1.6%). In group [3] the rate of postoperative complications, especially of infections, was unexpectedly low (e.g. fever > 38 degrees C in group [1]: 8.6%, group [2]: 11.5%, and in group [3]: 9.9%). This was not only explainable by more frequent prophylactic use, in group [3], of antibiotics whose efficacy in reducing infections was demonstrated. Altogether five patients died, two deaths, both in group [2], were directly related to cesarean section. Between 1978 and 1988 an increasing incidence of low birth weight infants was found in all groups, with the highest rate in group [3].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290282 TI - [Brain-specific creatine kinase (CKBB) in umbilical cord blood. A prognostic parameter in chronic intrauterine hypoxia?]. AB - Elevated levels of brain type creatine isoenzyme (CKBB) have been demonstrated in serum after brain cell injury in neonates. A hypoxic lesion of the membrane permeability of the CKBB rich brain cells may lead to an increased enzyme leakage into the serum. As an increased release from the fetal brain as a result of intermittent compression and decompression of the fetal head during labour and after rupture of membranes may occur without hypoxic damage, only pregnancies which were terminates by cesarean section were studied. No mother went into first stage of labour and no rupture of membranes occurred. Three study groups were defined. The control group (elective cesarean section for breech presentation) showed CKBB enzyme activities below 15 U/l. A group with emergency cesarean sections had low CKBB values too, despite acidotic pH-values (pH < 7.20) at birth. The third group included fetuses which were delivered by cesarean section because of a pathological fetal heart rate tracing and intrauterine growth retardation. 6 out of 40 umbilical cord sera in this group showed elevated CKBB enzyme activities. If there was an additional fetal acidosis an increased neurological morbidity and neonatal mortality was seen. PMID- 1290283 TI - [Three-dimensional analysis of the tunica media of umbilical arteries. Scanning electron microscopy study]. AB - The three-dimensional media structure of the umbilical arteries in their various functional states has up to now been object of numerous investigations, which are predominantly based on light-microscopic findings and have come to extremely differing results. For that reason the electron microscope method with an optically higher resolution was chosen for this thesis. In total, 20 umbilical cords were recovered, and in each case one of the two umbilical cord arteries was kept in a condition of non-contraction by means of perfusion fixation immediately after the omphalotomy. After the necessary preparation longitudinal, diagonal and cross-sections of both non-contracted and fully contracted umbilical arteries as well as of the folds of Hoboken, which occur in the arteries postnatally, were investigated by the scanning electron microscope. During this examination the following findings were made: The media in the wide umbilical cord artery consists of two layers. The outer layer accounts for some three quarters of the wall and is composed of lamellae of parallel muscle fibres which surround the vessel alternatively in gently rising and falling thread-like turns. The inner layer accounts for the remaining quarter and also consists of lamellae the thread like turns of which, however, run at a much higher pitch. Exactly subendothelial, a very thin layer of irregularly arranged fibres with longitudinal main direction can be clearly identified. The folds of Hoboken are caused by local media contraction in the course of which the outer media restructures itself, thus being the main carrier of the fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290284 TI - [Comment on the contribution: K. Goeschen: "Combined labor monitoring: maternal and fetal results]. PMID- 1290285 TI - [Heart failure, heart rate disturbances, pharmacologic prophylaxis]. PMID- 1290286 TI - [Heart failure, summary and perspectives]. PMID- 1290287 TI - [Pathophysiology of cardiac arrhythmias]. AB - Cardiac arrhythmias are ambiguous symptoms. Intracardiac as well as extracardiac alterations may be responsible. There is little direct information from the ECG concerning their pathophysiological mechanism. Bradycardic as well as tachycardic arrhythmias can be the result of two different fundamental disturbances: alterations of impulse formation (automaticity) or alterations of impulse conduction. Either one of these, or both of them acting together, may be responsible for the arrhythmia. Tachycardias due to disturbances of impulse formation may be brought about by enhanced firing of regular pacemakers (sino atrial node, av-node, ventricular conduction system), by abnormal automaticity occurring in ordinary atrial or ventricular myocardium, or by triggered activity due to early or delayed afterdepolarizations. Bradycardic disturbances of impulse formation are primarily concerned with sino-atrial nodal function. Bradycardic conduction disturbances mainly impair sinoatrial or atrioventricular propagation causing partial or total conduction block. Tachyarrhythmias due to disturbances of conduction are generated by re-entry of excitatory waves either along anatomically preformed pathways or around functional obstacles (refractory zones) with excitable gaps being more or less pronounced. On the cellular level, altered activities of ionic channels or transport systems play a significant part. Such changes are caused by: alterations of electrolyte composition (potassium, sodium, calcium), acidosis or alkalosis, autonomic and hormonal influences, membrane active metabolites (long-chain acylcarnitine, lysophosphatidylcholine), drugs (class I and III antiarrhythmics, cardiac glycosides) and poisons. In disturbances of conduction other aspects like geometry of pathways or cable properties (anisotropic conduction, coupling resistances between cells) are of particular significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290288 TI - [Principles for the classification of anti-arrhythmia agents in cardiac arrhythmias]. AB - Clinically useful antiarrhythmic drugs are a group of heterogenous compounds, both with respect to chemical structure and to cellular mechanism of action. The classification of antiarrhythmic agents according to Vaughan Williams is based on electrophysiological findings in isolated heart muscle and defines four classes of drug actions. The criteria for classification include blockade of ion channels (classes I and IV), interaction with receptors (class II), and alteration of electrophysiological parameters, e.g., prolongation in action potential duration (class III). Several antiarrhythmic drugs possess actions in more than one class. The classification does not include all established antiarrhythmics, e.g., digitalis. Class-I action is further subdivided on the basis of extent of Na+ channel block and additional change in action potential duration. The kinetics of the onset and offset of Na+ channel block can be explained by models in which association and dissociation from the receptor are functions of channel state, i.e., activated, inactivated or resting. Detailed analysis has led to the concept of saturation block (24). Recently, the European Society of Cardiology has presented a classification of antiarrhythmics based on a more comprehensive compilation of drug action (18). Any useful classification of antiarrhythmic agents should offer guidance for their clinical use. This goal has not yet been reached. The criteria of classification are physicochemical properties or cellular mechanism of action as detected with sophisticated electrophysiological techniques. However, in spite of this fact, successful therapeutic use of antiarrhythmic drugs remains, to a large extent, still empirical. PMID- 1290289 TI - [Evaluation of anti-arrhythmia agents in the animal model]. AB - In view of the results of CAST, researchers working in the field of experimental arrhythmia have been increasingly focusing on the quest for new anti-arrhythmic modes of action and ways of detecting pro-arrhythmic properties of antiarrhythmic drugs at an early stage. Here, the experimental methods available play a particularly important role. While trying to assess anti-arrhythmic effects without investigating electro-physiological parameters in isolated tissue would be inconceivable, the degree to which the results of in vitro studies can be transferred to the intact organism is limited because of the complex nature of the arrhythmias. Of the various existing in vivo models, the most commonly employed are those in which arrhythmia is induced after experimental surgical interventions causing ischemia and infarction, followed by reperfusion. This shows that researchers are striving to "create" pathophysiologically-defined conditions and, as far as possible, a pathophysiological situation which is similar to that in the patient. Guidelines were laid down for this model complex in the Lambeth Conventions (1988) in order to improve uniformity of the methods and better comparability of the results generated by different investigators. Of the existing arrhythmia models, the ventricular re-entry arrhythmia model after myocardial infarction triggered by programmed stimulation, which was devised by Spear/Moore (1983), has proven to be particularly useful in the assessment of antiarrhythmics and is used by many researchers. Class II and III antiarrhythmics can be identified reliably by this method, whereas class I antiarrhythmics are mostly inconspicuous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290290 TI - [The pro-arrhythmia effects of anti-arrhythmia agents--theoretical and clinical aspects]. AB - Proarrhythmic action of an antiarrhythmic drug is defined as 1) Worsening of preexisting arrhythmia (for example, increase of number of premature beats; frequency, rate, and duration of tachycardias at supraventricular or ventricular level); 2) induction of arrhythmias (supraventricular: for example, atrial tachycardia with block; ventricular: monomorphic or polymorphic ventricular tachycardia, torsade de pointes, ventricular fibrillation); 3) occurrence of bradycardia (sick sinus syndrome; atrioventricular and intraventricular conduction disturbances). The pathophysiology of proarrhythmic action is either facilitation of conduction block and reentry, or abnormal impulse formation. Induction of incessant monomorphic ventricular tachycardia or torsade de pointes is of special clinical relevance. Incessant ventricular tachycardia can be experimentally explained by an increase of functional conduction block and decrease of the wavelength of excitation (conduction velocity x refractory period) as actions favoring reentry; this is clinically most frequently seen with the application of class IC (and A)-drugs. Abnormal QT prolongation and torsade de pointes are most likely due to early afterdepolarizations of the cell membrane, and development of triggered activity; these arrhythmias are seen following the application of substances prolonging repolarization (class III and class IA-antiarrhythmic drugs). Independent of the precise electrophysiologic mechanism, arrhythmias may, under clinical conditions, also be provoked secondary to the negative inotropic action of these drugs. Proarrhythmic actions most frequently are concentration-dependent; rarely are they idiosyncratic. Usually, these side-effects are seen during the first days after initiation or increase of the antiarrhythmic drug dose; they may, however, manifest themselves only after a couple of months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290291 TI - [Clinical evaluation of new anti-arrhythmia drugs after the CAST (Cardiac Arrhythmia Suppression Trial) study]. AB - The results of the Cardiac Arrhythmia Suppression Trial (CAST) are of great importance for the development and clinical evaluation of new antiarrhythmic agents. Today, the development of a new antiarrhythmic drug is only justified, if the benefit risk ratio is superior compared to those agents already available in clinical practice. The primary criterion of therapeutic efficacy is the prevention of tachyarrhythmic sudden cardiac death and/or the prevention of sustained ventricular tachycardia. PMID- 1290292 TI - [Drug therapy of cardiovascular diseases. Heart failure. Introduction to the subject. Progress since 1982]. PMID- 1290293 TI - [Ventricular cardiac arrhythmias 1992. Summary and perspectives]. AB - The treatment of tachycardias has undergone marked changes. Doubts on the effectiveness and the benefits of antiarrhythmic drug therapy are the reason for a re-evaluation of the use of so-called class I- and class III-antiarrhythmic drugs. At the same time, there has been an increased awareness of new techniques for risk assessment; for instance, in postmyocardial infarction patients, not only the type and frequency of spontaneous arrhythmias but also other parameters like extent of left ventricular dysfunction, ventricular late potentials, inducible ventricular arrhythmias and effects of the autonomous nervous system should be considered. Serial electrophysiological testing to predict the efficacy of antiarrhythmic drug therapy has recently been challenged. Non-pharmacological approaches have been used in an increasing proportion of patients. Nevertheless, there is also an increasing interest in new antiarrhythmic drugs, especially those that prolong repolarization (class III). PMID- 1290295 TI - [Clinical pharmacology of acetylsalicylic acid]. AB - The pharmacological actions of acetylsalicylic acid (ASA) are determined by two compounds: ASA and salicylic acid. Salicylic acid is formed from its precursor ASA within 15-20 min after oral application and is responsible for the antiinflammatory, antipyretic, and analgetic activities of ASA. However, the platelet inhibitory, i.e., the antithrombotic action of ASA is only due to this compound itself and is caused by irreversible inhibition of the platelet cyclooxygenase, i.e., inhibition of thromboxane A2 formation. The bioavailability of plain ASA after oral administration amounts to 40-50% at therapeutic doses. This is due to rapid deacetylation prior to reaching the systemic circulation. This deacetylation accounts for a significant part of inhibition of platelet cyclooxygenase within the portal circulation which is further enhanced by using sustained-release preparations. Doses of 40-50 mg ASA per day are sufficient to maintain complete blockade of platelet cyclooxygenase and this agrees well with the established efficacy of 75 mg ASA/day in controlled clinical trials on secondary prevention of myocardial infarction. PMID- 1290294 TI - [Biochemical changes and disorders of electromechanical coupling in chronic heart failure]. AB - In the chronically failing heart, subtle biochemical alterations occur at the level of a number of subcellular systems. The cellular elements that control activation and inactivation of the contractile proteins are the plasma membrane and the sarcoplasmic reticulum (SR). During the plateau phase of the action potential the slow calcium channel is activated so that calcium ions enter into the interior of the cell and initiate--as a trigger signal in loco--the calcium release from the SR-calcium-stores. In the absence of catecholamines the measured calcium ion currents are similar when normal human myocardium is compared to end stage failing human myocardium. However, the increase in the calcium ion currents induced by maximum concentrations of catecholamines is significantly smaller in failing myocardium compared to normal myocardium. This observation can easily be explained by the down-regulation of the beta-1-adrenoceptors and the increase in the inhibitory Gi-proteins. In the failing myocardium, therefore, a beta-1 adrenoceptor stimulation leads to an insufficient increase in cyclic adenosine monophosphate so that the opening probability of the calcium channels is not appropriately enhanced. This results in a decreased contractile reserve. As far as is known today, the inactivation mechanisms of the plasma membrane (sodium calcium-exchanger, sodium-potassium ATPase, calcium ATPase) are not disturbed in the failing human myocardium. The calcium release from the SR can be quantified using either calcium indicators (aequorin, fura 2) or highly sensitive thermopiles. Both sophisticated heat measurements and fura-2 measurements indicated a decreased systolic calcium ion concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290296 TI - [Acetylsalicylic acid in unstable angina, after coronary revascularization and in prevention of cardiac thromboembolism]. AB - Acetylsalicylic acid (ASA) inhibits platelet function via cyclooxygenase inhibition. The selective inhibition of platelet cyclooxygenase is possible with the use of low doses of ASA due to presystemic acetylation of the platelet enzyme in the portal circulation. The clinical efficacy of ASA has been demonstrated for a number of indications. ASA reduces the rate of myocardial infarctions and cardiovascular deaths in patients with unstable angina. Simultaneous intravenous infusion of heparin has an additional positive effect. The prevention of acute coronary thromboses during PTCA and of early bypass graft occlusion has been convincingly demonstrated, if therapy is initiated immediately after surgery. Neither ASA nor any other drug has been effective in the prevention of late restenosis following PTCA and of late bypass graft occlusions. Thromboembolic complication after implantation of biological valve prostheses is significantly reduced by ASA, if no rheumatic valve disease is present. The rate of peripheral or cerebral thromboembolic events is markedly increased in patients with lone atrial fibrillation. In contrast to the very positive results obtained for anticoagulants, the reports with ASA were contradictory. ASA may be effective in preventing thromboembolic complications in younger patients with a lower risk or in elderly patients with contraindications for anticoagulation. For most clinical indications the efficacy of ASA has been demonstrated for doses of 75-324 mg/d. Following a loading dose of 300 mg on the first day, continuation of therapy with 100 mg/d should combine maximal therapeutic efficacy with a low rate of unwanted drug effects. PMID- 1290297 TI - [Thromboxane A2 and prevention of cardiovascular diseases]. AB - Thromboxane A2 (TxA2) is the main arachidonic acid metabolite in human platelets and exhibits two major activities; stimulation of platelet function, including secretion of platelet-derived storage products, e.g., 5-HT, PDGF, and vasoconstriction. Platelet hyperreactivity is typical for advanced stages of atherosclerosis and is paralleled by elevated circulating thromboxane levels. This is the target for TX-antagonistic compounds. Three classes of selective compounds are available: inhibitors of thromboxane synthase, antagonists of thromboxane receptors, and mixed-type agents. Positive experimental data with all of these compounds are available. However, clinical experience is limited and, in general, not convincing. This review discusses possible reasons for that and suggests that, in particular, the use of combined-type agents as antithrombotics may be superior to acetyl-salicylic acid in several forms of ischemic cardiovascular diseases. PMID- 1290298 TI - [Prevention of cardiovascular diseases by intervention in lipid metabolism]. AB - Atherogenesis is a multifactorial event. Experimental, clinical and epidemiological studies, however, have clearly indicated the major role of LDL cholesterol in the process of cholesterol deposition in the arterial wall. Although most patients with severe hypercholesterolemia suffer from premature coronary heart disease, it is a medical experience, that there are subjects who tolerate hypercholesterolemia and reach high ages without problems of their coronary arteries. Thus, there is much biological variation in the response of the arterial wall to elevated LDL-cholesterol, a fact which emphasizes the need to differentiate between goals and means of primary and the goals and means of secondary prevention of coronary heart disease and between the goals of a population strategy and the goals and means of an individual therapeutic strategy. Today the knowledge about the role of lipids and lipoproteins in atherogenesis is convincing. Epidemiological as well as intervention studies have proven the benefit of an appropriate lipid lowering therapy. PMID- 1290299 TI - [Prevention with vasoactive drugs]. AB - Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also to improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine (also under clinical conditions) if coronary flow reserve can be improved, in 30 hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with an ACE-inhibitor (enalapril 10-20 mg/d), a calcium channel blocker (diltiazem 120-180 mg/d) and a beta 1-selective beta-receptor-blocker (bisoprolol 5-10 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a comparable decrease in LV muscle mass, coronary reserve was improved after enalapril by 48%, after diltiazem by 48%, and after bisoprolol by 22%. It is possible that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities on the level of the coronary microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290300 TI - [Prevention with angiotensin-converting enzyme (ACE) inhibitors]. AB - Preventive therapy by angiotensin-converting-enzyme (ACE) inhibitors is considered in hypertension and, more recently, in chronic heart failure. The mechanism of action of ACE-inhibitors is complex; most extensively studied, however, is their inhibitory effect on angiotensin-II production. ACE-inhibitors may act as vasodilators, reducing pre- and afterload. On the other hand, local renin-angiotensin systems may control growth processes both in myocardial and in smooth muscle cells. This may be another site of action for ACE-inhibitors. ACE inhibitors are reliable antihypertensive drugs and may have additional specific effects on the heart and vascular smooth muscle. Clear evidence is, however, missing for their superiority above other drugs in preventing cardiovascular complications of hypertension. Most recently, the data of the "study of left ventricular dysfunction" (SOLVD) and "survival and ventricular enlargement" (SAVE) study became available. These studies showed that ACE-inhibitors could prevent the incidence of heart failure in about one-third of patients with severe left-ventricular dysfunction during 3 years of observation when compared with placebo treated patients. A new indication, therefore, for ACE-inhibitors could be left ventricular dysfunction after myocardial infarction. It remains unclear 1) what could be the adequate diagnostic procedures to identify patients for preventive treatment, 2) when therapy should be started, 3) about the duration of therapy, 4) about the doses of ACE-inhibitors for this indication, 5) what will be the side-effects when used in a broader population, and 6) will this prevention of heart failure be a specific effect of ACE-inhibitors? PMID- 1290301 TI - [Pharmacologic prevention of cardiovascular diseases with calcium antagonists]. AB - The major impact of calcium-antagonists in prevention strategies of cardiovascular disease evolves from their modulation of signal transduction and metabolic processes controlled by calcium-ions as "second messenger" in cells participating in the early development of vascular atherosclerotic lesions, namely endothelial cells, vascular smooth muscle cells, monocytes/macrophages, T lymphocytes and platelets. In accordance with experimental data suppression of angiographically early coronary lesions was documented in four independent clinical studies using quantitative analysis of repeated coronary angiography: Nifedipine and Nicardipine reduce angiographically "new" (minimal) lesions to 30 70%, in some cases already after 1 year of treatment. This anti-atherosclerotic effect is independent of known risk factors and indicates a new strategy in "primary" prevention of atherosclerotic vascular disease. In pre-infarction syndromes calcium-antagonists demonstrate a tendency in attenuating anginal symptoms and progression into definitive infarction. Analysis of studies in acute infarction showed a neutral effect of calcium-antagonists with unchanged infarct size, regional and global ventricular function or early mortality. In post infarction patients only strict selection criteria (up to 60% of patients) as well as delayed onset of therapy (> 7 days after infarction) reduce the number of re-infarction and mortality. Subgroup analysis indicate that calcium antagonists with mild afterload reduction and minimal negative inotropic impact might be preferable. The suppression of "early" lesions should be regarded as the predominant benefit for future strategies in prevention of cardiovascular disease with calcium-antagonists. PMID- 1290302 TI - [Pharmacologic prevention of cardiovascular diseases. Summary and perspectives]. PMID- 1290303 TI - [The freedom of research and the responsibility of the scientist]. PMID- 1290304 TI - [Changes in gene expression in terminal myocardial failure]. AB - End-stage human heart failure is the common final manifestation of a group of heterogeneous diseases, and it is usually accompanied by myocardial hypertrophy. Studies on animal models have shown that myocardial hypertrophy is an adaptational process accompanied by characteristic changes in the expression of cardiac genes: reinduction of fetal isoforms of the myofilaments actin and myosin, downregulation of SR Ca(2+)-ATPase and phospholamban, downregulation of beta-adrenoceptors and increased expression of inhibitory G proteins (Gi). These alterations lead to reduced shortening velocity, slowed relaxation, and to desensitization of adenylyl cyclase, thereby probably increasing myocardial economy and lowering energy demand. Gene expression in human end-stage heart failure due to dilated cardiomyopathy exhibits some clear differences, but also significant parallels to gene expression in experimental hypertrophy: there is no isoform shift because fetal isoforms of the myofilaments are already predominant in the adult ventricle. However, like in animal models expression of SR Ca(2+) ATPase and phospholamban is decreased, correlating with slowed relaxation of the diseased myocardium, beta-adrenoceptors are downregulated, and the expression of Gi is increased, leading to desensitization of the adenylyl cyclase pathway. These results suggest that alterations of gene expression in human end-stage myocardial failure, known so far, are secondary to chronic overload and are not a primary cause in the pathogenetic process. They are probably initially favorable adaptive processes to chronic overload, but finally cause a further deterioration of contractile performance of the myocardium. PMID- 1290305 TI - [The significance of myocardial hypertrophy in heart failure]. AB - Myocardial hypertrophy in response to elevated myocardial wall stress largely results from myocyte hypertrophy. In congestive heart failure, this hypertrophy can have compensatory as well as critical relevance. On the one hand, it reduces myocardial wall stress in the case of hemodynamic overload by enhancing ventricular wall thickness. On the other hand, risks and problems may result from the tissue changes associated with myocardial "overload-hypertrophy", such as alterations in myocyte phenotype, augmentation of connective tissue in the myocardium, reductions in coronary reserve (even without altherosclerotic coronary stenoses), and alterations in the local formation of growth cofactors (i.e., enhanced myocardial expression of angiotensinogen and converting enzyme). Changes in myocyte phenotype occur in receptor signal transduction, in isoform shifts of contractile proteins and of key enzymes in energy metabolism towards a more fetal-like pattern, and in a "fragility" of Ca(++)-homeostasis (due to reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and enhanced expression of membrane Na+/Ca(++)-exchange in presence of maintained density of Ca(++)-channels). Additionally, the fraction of contractile fibers and mitochondria per myocyte cross-section can be reduced with attenuated systolic function. The fragility of Ca(++)-homeostasis must be regarded as potentially critical because of retarded inactivation of contraction and because of susceptibility to diastolic Ca(++)-overload with delayed after-depolarizations. Additionally, diastolic dysfunction may result from interstitial fibrosis and ischemia due to reduced coronary reserve (altered vascular structure and endothelial dysfunction).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290306 TI - On the role of Ca++ binding proteins as possible targets for Ca++ sensitizing agents. AB - We describe the effects of various cardioactive compounds on the Ca++ activation of force production and ATPase activity in isolated contractile structures from mammalian heart and, in some cases, skeletal muscle. We show that: 1) the Ca++ sensitizing activity of APP 201-533 does not discriminate between cardiac and skeletal muscle and is, therefore, not based on interaction with cardiac troponin I phosphorylation at serine 20. 2) compounds like trifluoperazine or bepridil, both known to interact with calmodulin, increase the Ca++ sensitivity of the contractile structures of the heart, in high concentrations, as expected from the high natural abundance of troponin C. 3) DPI 201-106 interacts with calmodulin (and presumably with the structurally closely related troponin C) in the microM concentration range. Its high Ca(++)-sensitizing potency in skinned cardiac muscle and a certain sensitivity of this effect to the detergent Triton X-100 suggest accumulation of the hydrophobic compound in the myofibrillar protein lattice. PMID- 1290307 TI - [New cardiotonic/inodilator agents: energetic aspects]. AB - Inotropic agents alter myocardial oxygen consumption by influencing heart rate, by influencing preload and afterload due to vasodilation, and by direct effects on the myocardium. The latter critically depend on the pharmacologic mode of action. Inotropic agents which act by increasing cyclic AMP in the failing human myocardium increase myocardial energy turnover by their effects on excitation contraction coupling, resulting in a considerable increase in the amount of calcium cycling. Glycosides, which increase contractile force independent of cyclic AMP, increase calcium cycling moderately and do not influence myocardial energy turnover significantly. Calcium-sensitizers, by increasing calcium affinity of contractile proteins, may increase contractile force and decrease myocardial energy turnover. Peripheral vasodilation following the application of inotropic agents decreases myocardial oxygen consumption due to a decrease in systolic stress-time integral. The energy-saving effect of reduced preload and afterload may counterbalance a direct myocardial energy-wasting effect of some inotropic agents. An increase in heart rate due to inotropic interventions is unfavorable since 1) oxygen consumption increases in proportion to heart rate, and 2) contractile force of the failing human myocardium decreases. The latter was obvious from experimental and clinical studies showing that increasing heart rate increases contractile force and cardiac output in nonfailing human myocardium, but decreases cardiac performance in the failing human heart. In light of the inverse force-frequency relation in failing human myocardium, negative chronotropic drugs may represent a new class of "positive inotropic" agents. Agents reducing heart rate may be beneficial from an energetic point of view by reducing myocardial oxygen consumption and by improving myocardial perfusion due to a prolongation of diastole. PMID- 1290308 TI - [The value of ACE inhibitors in heart failure (mechanism of action)]. AB - ACE-inhibitors improve symptoms and prognosis in patients with heart failure. The V-Heft II trial has demonstrated that the beneficial effect of these agents is superior to unspecific vasodilators. Besides sustained arterial and venous vasodilation the inhibition of the neurohumoral axis is thought to play an important role. Angiotensin II and catecholamines not only exert vasoconstrictor effects, but might also contribute to vascular and myocardial growth. Thus, it may not be surprising that the beneficial effects of ACE inhibitors in heart failure only emerge during long-term therapy rather than after short-term administration. It has been shown that these agents improve blood flow to skeletal muscle during exercise after chronic therapy (not acutely), and there is some preliminary evidence that improvement of endothelial function might be involved in this effect, i.e., by reducing the degradation of bradykinin, an endothelial vasodilator. ACE inhibitors reduce LV hypertrophy, an important risk factor for cardiovascular disease and prognosis. Moreover, there is experimental evidence that ACE inhibitors can prevent and even reverse interstitial fibrosis in the left ventricle. Although the plasma renin activity may be normal in patients with chronic heart failure, recent data using polymerase chain reaction indicate that the tissue cardiac renin angiotensin system is activated in the failing human heart as assessed by measurements of angiotensin converting enzyme mRNA and angiotensinogen mRNA which may be an important target for ACE inhibition. PMID- 1290309 TI - [Value of ACE inhibitors in heart failure (clinical aspects)]. AB - The use of ACE-inhibitors in patients with severe congestive heart failure is established on the basis of the results of the CONSENSUS I-study, which has shown that ACE-inhibitors in patients in NYHA class IV not only have improved functional parameters, but also improved survival. Recently published controlled data from studies including patients with mild to moderate heart failure (SOLVD study) show a significant improvement of mortality in this subgroup. Comparing placebo and ACE-inhibitors, the effect of ACE-inhibitors on mortality is due to a reduction of progression of pump failure. Comparing vasodilator-therapy (hydralazine/isosorbide dinitrate) and ACE-inhibition in the V-HeFT II-trial showed, despite a transient increase in ejection fraction and exercise capacity during the vasodilator-therapy, a significant improvement in survival in the patients treated with an ACE-inhibitor. This was achieved by a reduction of the incidence of sudden cardiac death. From these recent data it can be concluded that ACE-inhibition is the therapy of choice in patients with mild to severe heart failure. PMID- 1290310 TI - [Clinical aspects of differential drug therapy of chronic heart failure]. AB - Treatment of chronic heart failure with ACE-inhibitors has greatly improved the prognosis. In addition to ACE-inhibitors, diuretics seem to be necessary to decrease mortality, whereas the importance of cardiac glycosides has not been demonstrated unequivocally. Nevertheless, modern treatment of chronic heart failure in all stages should be a combination of diuretics, digitalis, and ACE inhibitors rather than a stepwise addition of drugs depending on the severity of the disease. An increased heart rate leads to increased myocardial O2 consumption, decreased O2-supply, ischemia, and reduced contractility. Betablocker-induced reduction of heart rate does, however, not necessarily improve symptoms or hemodynamic conditions. The optimal heart rate in large failing hearts is not known yet. Probably, it is dependent on the type and severity of myocardial disease or impairment. In this respect, the sarcoplasmatic release and uptake of Ca2+ plays the most important role in the disordered force frequency-relation in chronic heart failure. PMID- 1290311 TI - [Proceedings of the 22nd annual meeting of the Japanese Society of Neuropsychopharmacology. Sapporo, October 8-9, 1992]. PMID- 1290312 TI - In memoriam Cesare Bartorelli (1911-1991). A pioneer in the field of arterial hypertension. PMID- 1290313 TI - Time course of serum lipid and lipoprotein levels after coronary bypass surgery: modification by pravastatin. AB - The time course of the changes in serum lipid and lipoprotein levels have been studied in 100 patients undergoing coronary artery bypass surgery. Marked decreases occur in the levels of cholesterol (-45%), HDL-cholesterol (-35%), LDL cholesterol (-53%), Apo A1 (-43%) and Apo B (-43%) on the third day after the operation. In the control group the values gradually returned to preoperative levels which are reached after three months. Three months after the intervention, in the pravastatin-treated group (20 mg/day) the values of total cholesterol ( 20%), LDL-cholesterol (-28%) and Apo B (-22%), remained significantly lower than in the control group (p 0.0001) and were lower over the whole duration of the study. The postoperative time course of HDL-cholesterol and Apo A1, however, was not significantly influenced by the administration of pravastatin. PMID- 1290314 TI - Time course of serum Lp(a) in men after coronary artery bypass grafting. AB - The serum Lp(a) time course was studied in 100 male patients who underwent coronary artery bypass grafting (CABG). The patients were randomized in a placebo (N = 50) and pravastatin treated (N = 50) group. The pravastatin regimen was 10 mg daily from the third postoperative day on and 20 mg daily after 1 week during 11 weeks. Lp(a) levels and serum lipids were analyzed at baseline, at 3 and 10 days, and at 4 and 12 weeks post-CABG. A decrease of serum Lp(a) levels at the third postoperative day was seen which parallels the changes noted with the other serum lipids when using extracorporeal circulation. In contrast with the other serum lipids, a slight but significant Lp(a) overshooting was noticed at day 10 followed by a decrease of the serum Lp(a) levels to preoperative levels 1 month after the acute event. The study clearly depicts that there is a significant time dependent effect on the serum Lp(a) levels post-CABG and that there is no effect of treatment (pravastatin). The data also reveal that reliable postoperative Lp(a) measurements can be made at earliest 1 month post-CABG. PMID- 1290315 TI - The diet and moderate exercise trial (DAMET): results after 24 weeks. AB - W.H.O. and U.S. Dept. of Health and Human Services advocate a fat-modified, fruits and vegetable-enriched diet in conjunction with mode-rate physical activity for fitness and health. The Diet and Moderate Exercise Trial (DAMET) is a randomized and controlled study and has provided scientific proof, possibly for the first time, to the above hypothesis (based on epidemiologic studies, short clinical trials and experimental studies) that the new approach can cause modulation of risk factors of coronary heart disease (CHD) as well as improve fitness. In the DAMET, 231 group A and 232 group B patients with risk factors of CHD were administered a prudent diet for 4 weeks, group A patients in addition were also given at least 400 g/day of fruits and vegetables that are rich in dietary fibre and antioxidants such as vitamins A, C, E, carotene and copper, selenium and magnesium. Fruits and vegetables were administered in a foods-to-eat approach by asking the patients to eat these foods before meals when they were hungry to allow better nutrient adequacy. After 4 weeks, group A patients also did moderate exercise such as brisk walking and spot running compared to no such advice to group B for another 20 weeks. After a follow-up period of 24 weeks, adding exercise to diet was associated with a significant decrease in blood total cholesterol (8.9%) and LDL-cholesterol (6.7%) and triglycerides (11.9%) and a marked increase in HDL-cholesterol (16.5%). Mean blood pressures, fasting blood glucose, body weight, body mass index, waist-to-hip ratio and subcutaneous fat also showed a significant decrease in group A, leading to a significant decrease in 12-year CHD risk. A long-term follow-up may be necessary to demonstrate the role of this new approach in decreasing cardiovascular morbidity and mortality. PMID- 1290316 TI - [Hypoglycemia in diabetes mellitus]. AB - Type 1 diabetic patients experience symptomatic hypoglycemia once or twice a week. 30% of insulin-treated patients suffer from hypoglycemic coma at least once during their life, 10% at least once a year. 3% are incapacitated by frequent and severe attacks, 3 to 4% die from hypoglycemia. In contrast the incidence of symptomatic hypoglycemia in sulfonylurea-treated patients is about 0.2 per 1000 patients' years, the mortality of severe attacks being about 8%. The cause of hypoglycemia is always an excess of insulin, in absolute or relative terms. Additional precipitating factors are defective counterregulation after longer duration of diabetes, as well as a lowered threshold for counterregulation and/or for perception of warning symptoms, as seen under strict glycemic control. Considering the risks associated with hypoglycemia, preventive measures must be emphasized. PMID- 1290317 TI - [Is the patient with respiratory failure adequately cared for these days?]. AB - Pulmonary function studies in 20,000 non-clinical probands throughout Austria showed abnormal findings in 20%. This is further evidence that chronic obstructive pulmonary disease (COPD) is epidemiologically similar to coronary heart disease. A staging classification of COPD has been proposed to facilitate a strategy for the prevention of the disease and to permit coordination among general practitioners, specialists and pulmonary function laboratories. This initiative aims to reduce the prevalence of advanced (stage IV) COPD. In the meantime long-term oxygen therapy and respirator therapy should be used increasingly to improve the quality of life of patients with advanced COPD. PMID- 1290318 TI - [Functional and clinical differentiation of chronic respiratory failure]. AB - Respiratory insufficiency is defined as hypoxemia due to bronchopulmonary disorders. The site of the underlying disease can be exclusively in the parenchyma and vessels of the lung, but also in the pumping mechanisms with resulting CO2-retention. A combination of these phenomena is usually seen in patients of the predominant bronchitic Type B of chronic obstructive lung disease. Vascular and parenchymatous lesions cause hypoxemia by decrease of diffusion capacity, distribution inequality of blood flow and ventilation, and also shunting mechanisms. CO2-retention is not to be expected in these cases. The therapeutic approach is based on the individual predominance of functional findings in a given patient, and include medication to relieve bronchial obstruction, substitution of oxygen and measures for mechanical support of breathing. Especially bronchial obstruction should be identified as early as possible in the course of the disease in order to prevent inevitable and irreversible morphological changes. PMID- 1290319 TI - [Conventional therapy exemplified by COPD]. AB - Conventional therapies are those, that are generally agreed on and applied. With COPD these are strongly anti-inflammatory corticosteroids, bronchodilatant betamimetics, vagolytics and theophyllines, within certain indications antibiotics, secretolytics and secretomotorics, physical therapy and therapy of secondary effects. At present those measures, that might mitigate the status of patients importantly, e.g. patient training and beyond this early diagnosis and therapy to improve the prognosis are still unconventional. Prophylactic measures, importantly influencing pathogenesis and progression of the disease, would be of special importance. Prevention of cigarette smoking would show the greatest benefit. It would be desirable, that these unconventional measures would be more widespread in use than is presently the case. PMID- 1290320 TI - Intravenous therapy of chronic obstructive pulmonary disease with sodium glycinate theophylline monitored by a new bed side theophylline assay. AB - Although the therapy of airway obstruction with theophylline is well established, unwanted side effects can occur: overdosage and reactions to ethylendiamine, an additive to increase the solubility of theophylline. Frequent measurements of the theophylline blood levels and the use of ethylendiamine free preparations can avoid such problems. Therefore, we studied the validity of a new immunochromatographic bed side assay (Acculevel) prior and after infusion of sodiumglycinate-theophylline (Theospirex) in 13 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Although theophylline levels increased above the therapeutic range (20 mg/L) in half of the patients after the infusion of 400 mg Theospirex in 1 hour, no toxic effects could be denoted. In addition, no influence on blood pressure and heart rate were found. We observed good correlations between this new immunochromatographic assay and theophylline levels measured with 2 well established reference methods (HPLC and turbidimetry, r = 0.87 and 0.91, respectively), although Acculevel revealed slightly higher values. Thus, the use of sodium-glycinate-theophylline and the new, fast bed side test system seems of practical importance in the therapy of COPD by potentially avoiding undesirable side effects. PMID- 1290321 TI - [Genetic principles of malignant transformation]. AB - Genetic alterations such as translocations, deletions or point mutations often result in a loss of function. Such alterations may contribute to oncogenesis by interference with mechanisms restraining cellular growth. However, mutations of protooncogenes can also result in abnormal positive signals for cell proliferation. Some concepts resulting from genetic approaches to identify the genes that may be involved in the regulation of cell multiplications are discussed. PMID- 1290322 TI - [Insulin resistance]. AB - Insulin sensitivity of insulin dependent tissues (muscle, adipose tissue, liver) is subject to a variety of influences. Any change in insulin sensitivity is compensated in healthy subjects by a dynamic change in insulin secretion, which will decrease following a rise in insulin sensitivity and increase if insulin sensitivity is impaired (i.e. during insulin resistance induced by obesity, pregnancy, oral contraceptives, dehydration, saturated fatty acids, fever, drugs, etc.). In contrast to secondary insulin resistance idiopathic insulin resistance in type 2 diabetic individuals is associated with impaired insulin secretion, which thus is unable to overcome impaired insulin sensitivity. Idiopathic insulin resistance in type 2 diabetes is additionally characterized by reduced glucose storage, the basis of which may reside in an insulin receptor defect, in the presence of insulin receptor antibodies, in a postreceptor defect or in the synthesis of abnormal insulin molecules. PMID- 1290323 TI - Correlation between mitochondrial enlargement in renal proximal tubules and microalbuminuria in rats with early streptozotocin-induced diabetes. AB - To clarify the ultrastructural changes in renal proximal tubules causing microalbuminuria in the early stage of diabetic nephropathy, three different groups of rats were prepared: rats with streptozotocin (STZ)-induced diabetes given no treatment (DMut; n = 7), rats with STZ-induced diabetes treated with insulin (DMt; n = 7), and non-diabetic rats injected with citrate buffer (control; n = 7). In each group, the laboratory findings, ATP content of the renal cortex, and the size of proximal tubule cells and their nuclei and mitochondria (MT) were determined. In two weeks after the start of the study, MT in renal proximal tubules showed diffuse enlargement in the DMut group as compared with those in the control group. Renal cortical ATP content, fractional sodium excretion (FENa), urinary excretion of beta 2-microglobulin and albumin were also increased significantly in the DMut group relative to the controls. In the DMt group, most of the examined parameters returned almost to normal. There were positive correlations between each of the following parameters: hyperglycemia and MT enlargement, MT enlargement and increased cortical ATP content, increased cortical ATP content and increased FENa, increased FENa and increased urinary excretion of beta 2-microglobulin and albumin. On the basis of these results, we conclude that mitochondrial enlargement, resulting from disturbed metabolism of ATP, may reduce active transport in renal proximal tubules, which, in turn, may impair reabsorption in the tubules. This would cause urinary excretion of low-molecular-weight proteins and microalbumin in the early stage of diabetic nephropathy. PMID- 1290324 TI - Changes in spermatozoa due to large doses of pyridoxine (vitamin B6). AB - To investigate the changes of spermatozoa by high doses of vitamin B6 (B6), the alterations in spermatozoa and testis of rats after the administration of high doses of B6 were evaluated quantitatively and morphometrically. Wistar rats of 11 weeks of age were intraperitoneally injected with 63, 125, 250 and 500 mg/kg of B6 daily 5 times per week for 6 weeks. Using the spermatozoa taken from the epididymis and ductus deferens, the number, motility and nuclear morphology of spermatozoa were examined. After preparing 7 parameters for the nuclear morphology, the morphometry was performed by an IBAS version 2 (Zeiss) image analysis system. The number of spermatocytes and spermatids in representative stages of spermatogenesis was counted per Sertoli cell histologically. Mild deformation of spermatozoa nuclei occurred in the 63 mg or more exposure groups. In the 125 and 250 mg groups, the decrease in number as well as motility of spermatozoa together with slight decrease of spermatids in late maturation phase (mature spermatids) and the delay in spermiation appeared. Phagocytosis of mature spermatids by Sertoli cells was clearly increased in the 250 mg group. The alteration and the decreased number of spermatozoa are suggested to have mainly resulted from alteration of mature spermatids and the increased phagocytosis of mature spermatids by Sertoli cells. Computer-assisted morphometry of spermatozoa nuclei was useful not only to evaluate morphological changes objectively but also to discern them early. PMID- 1290325 TI - Pancreatic islet abnormalities in sudden infant death syndrome. Qualitative and quantitative analyses of 15 cases. AB - The pancreata of 15 autopsy cases of sudden infant death syndrome (SIDS) and those of 14 age-matched controls were examined qualitatively and quantitatively to re-evaluate the relationship between pancreatic islet abnormalities and sudden death in infancy. Histopathologically, a diffuse or focal form of nesidioblastosis and septal islets were frequently observed in the pancreata of both groups. Endocrine cell dysplasia was found only in 2 infants who had died of SIDS. Quantitatively, there was little difference of islet cell composition between the SIDS cases and the controls. A relatively high proportion of islet cell area to total pancreatic tissue area was demonstrated in the SIDS group (8.46 +/- 4.90% in the pancreatic head; 8.66 +/- 4.23% in the pancreatic body to tail) in comparison with the controls (5.32 +/- 1.77%; 5.63 +/- 1.60%). Although nesidioblastosis and septal islets were considered to be within the limits of normal variation during pancreatic development, endocrine cell dysplasia and quantitatively unusual proliferation of the pancreatic endocrine tissue suggest the possibility that abnormalities in the endocrine pancreas may be causally related to sudden death in infancy. PMID- 1290326 TI - Pulmonary blastoma. Comparison between its epithelial components and fetal bronchial epithelium. AB - Three cases of pulmonary blastoma exhibiting biphasic epithelial and stromal patterns, and a case of fetal lung-type adenocarcinoma, were examined by immunohistochemistry and electron microscopy (EM) and compared with fetal bronchial epithelium in order to explore the multidirectional differentiation of their epithelial components. The glandular cells of all four tumors resembled fetal bronchial epithelial cells in the pseudoglandular stage. Neuroendocrine (NE) cells were also present; they were argyrophilic and expressed pan-NE markers, neurosecretory granules and peptide hormones. The neural cell adhesion molecule (NCAM) was strongly expressed on the cell membranes of glandular cells, as in the case of proximal bronchial epithelial cells at the pseudoglandular stage in fetal lung. Sialosylated Lewis X was also expressed, indicating that the epithelial cells were possibly of endodermal origin. Two of the four cases showed considerable immunoreactivity for alpha-fetoprotein (AFP). The epithelial cells of pulmonary blastomas may occasionally de-differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP. Tumor examination by immunohistochemistry and EM suggested that the glandular cells of the tumors may differentiate to some extent like those of fetal large bronchi at the pseudoglandular stage, but there was concordance and discordance in the expression of neuroendocrine and oncofetal markers between blastomatous tumors and fetal bronchial epithelium. PMID- 1290327 TI - Multinodular deposition of AA-type amyloid localized in the adrenal glands of an old man. AB - Multinodular amyloid deposits localized in non-neoplastic adrenal glands were found incidentally at autopsy in an 83-year-old Japanese man. Clinically, the patient lacked evident deficiency of adrenal hormones. The nodules of the stromal amyloid deposits were scattered in the adrenal cortex, where the parenchymal cells were compressed and atrophic. The deposits were confirmed to be amyloid by Congo red staining and polarization microscopy. Amyloid fibrils were also demonstrated in the deposits by electron microscopy. The amyloid deposits were permanganate-sensitive and showed immunohistochemical staining for serum amyloid P component and serum amyloid A protein (SAA), implying that they were AA amyloid. There have been no reports describing localized amyloid deposits of the AA type in non-neoplastic adrenal glands. The pathogenesis and clinical significance of the amyloid deposition in the present case remain only speculative. PMID- 1290328 TI - A case of intramural uterine stromal tumor with epithelial differentiation. AB - A case of intrauterine tumor in a 62-year-old Japanese woman is presented. It was thought initially that this was a case of uterine tumor resembling an ovarian sex cord tumor. To examine the cytological features of the tumor cells, electron microscopical and immunohistochemical studies were done, and a hormone assay of the tumor tissue was performed. The tumor cells were rich in rough endoplasmic reticulum (rER), mitochondria and microfilaments. Some tumor cells tended to form glandular patterns, but these epithelial elements were frequently scattered among fibrous stromal elements. Though many tumor cells with an epithelial appearance possessed a large quantity of cytokeratin and vimentin, they did not secrete estradiol, progesterone, testosterone or human chorionic gonadotropin. This case was finally diagnosed as an intramural uterine stromal tumor with epithelial differentiation after taking all the available data into consideration. This would be classified as an endometrial stromal tumor with epithelial elements, recently proposed and named by Clement and Scully. PMID- 1290329 TI - Evaluation of the performance of the copper T380A IUD up to ten years. Is this IUD a reversible but potentially permanent method? AB - The clinical experience of a cohort of 340 women using a TCu380A IUD for up to 10 years at the Family Planning Clinic of the State University of Campinas, Brazil was evaluated by life-table analysis. Removals for medical reasons were more frequent during the first year of use, while from the third year on, removals for personal reasons were more frequent. Expulsions were concentrated in the first two years of use, and none were detected after the fourth. Gross pregnancy rate accumulated to 2.0, 2.8 and 5.3 and continuation rate was 64.2, 43.4 and 27.8 per 100 women at three, six and ten years of use, respectively. The effectiveness of the device did not decrease significantly after the eighth year of use and it could be considered a reversible but potentially permanent method. PMID- 1290330 TI - Immediate postpartum intrauterine device insertion--a report on the Chinese experience. AB - Immediate postplacental insertion (IPPI) of the intrauterine device (IUD) has been practiced in China for at least 17 years. This presentation reviews and integrates the clinical experiences of IPPIs at five Chinese centers. The stainless-steel ring IUD was the most commonly used device for this procedure. Our review indicates that: (a) IPPIs-both after vaginal delivery and at cesarean section-are medically safe and effective in preventing accidental pregnancies (given careful patient selection), and (b) the one-year life-table expulsion rates of IUDs inserted at cesarean section are lower than the rates for vaginal insertions after normal delivery. This review also discusses other issues, such as factors influencing expulsion rates. Generally, IPPIs, whether performed via vagina or cesarean section, seem to be a method of choice for postpartum contraception. Some findings are, however, tentative; thus, further studies are needed. PMID- 1290331 TI - Comparative assessment of two low-dose oral contraceptives, Lo-Femenal and Lo Estrin, in Mexican women. AB - This trial was designed to determine the differences in effectiveness, clinical acceptability, and one-year discontinuation rates of two low-dose oral contraceptives: Lo-Estrin (norethindrone acetate 1.5 mg plus ethinyl estradiol 0.030 mg) and Lo-Femenal (norgestrel 0.30 mg plus ethinyl estradiol 0.030 mg) in 148 Mexican women. In addition, the effects of both oral contraceptive preparations on blood lipids were prospectively evaluated in a subgroup of 41 women. The results indicated that there were no differences in pregnancy rates, discontinuation or clinical acceptability between the two groups. The lipid changes observed were minimal for the Lo-Femenal subgroup and somewhat greater for the Lo-Estrin group, mainly an increase in serum triglycerides. These changes were interpreted as estrogen induced effects of norethindrone-containing oral contraceptives. Overall, the data indicate that both Lo-Femenal and Lo-Estrin are effective and safe combined oral contraceptives. PMID- 1290332 TI - An evaluation of IUD insertion by a non-clinical delivery system. AB - To evaluate the safety, effectiveness, side-effects, and continuation rate associated with non-clinical IUD insertion compared to IUD insertion in routine clinical facilities, a cohort comparative study was done on two groups of IUD users self-selected for either the non-clinical or clinical delivery system in Yogyakarta Special Area Province. During the months of January to March 1985, 454 non-clinical and 625 clinical acceptors were recruited into this study. However, only 414 non-clinical and 605 clinical acceptors fulfilled the inclusion criteria and were included in the analysis. Bleeding and pain were the most common side effects reported by acceptors. The frequency of bleeding was higher in the non clinical group than in the clinical group. However, the difference was a not statistically significant relative risk (RR) of 1.09 (0.8-1.4) to 1.2 (0.9-1.5). Severe menstrual blood loss mostly occurred in the first three months after insertion and then declined in the rest of the year in both groups. The frequency of pain was not clearly different between the two groups during the whole year, with RR 0.8 (0.5-1.3) to 1.3 (0.8-2.0). The actual number of pregnancies was very small and the difference was not statistically significant (p = 0.375). The 12 month expulsion rates were 7.22 per 100 IUD users for the non-clinical group and 7.00 for the clinical group. The difference was not statistically significant (p = 0.660). The cumulative probability of women who were still using IUDs at 12 months was 89.7% and 89.1% for the non-clinical and clinical groups, respectively. The non-clinical delivery system seemed to be responsive to an unmet demand for family planning among women with lower educational background compared with those in the clinical setting service. While the characteristics of a population obviously influence the contraceptive behavior, this study shows that the non-clinical delivery system family planning method provides a similarly efficacious and safe service to the usual clinical system. PMID- 1290333 TI - The possible relationship between menorrhagia and occult hypothyroidism in IUD wearing women. AB - A high incidence of occult hypothyroidism in menorrhagic women has been reported and emphasized in recent studies. In order to verify this statement, we have evaluated the functional status of the thyroid gland in intrauterine device (IUD) wearers suffering from increased menstrual bleeding. The study group consisted of 40 IUD-wearing women, aged 26-46 years, suffering from metrorrhagia. The control group consisted of 38 IUD-fitted women, 22-44 years old, in whom menstrual bleeding was not significantly increased. Menorrhagia was defined as excessive vaginal bleeding lasting for 6 days or more, and/or containing a significant amount of blood clots. Free thyroxine (FT) and thyroid-stimulating hormone (TSH) levels were assessed. FT levels were identical in both groups and within the normal range (1.31 +/- 0.28 ng/dl). TSH levels were significantly higher in the study group than in the controls, although they remained within the normal range (2.75 +/- 2.06 vs. 1.45 +/- 0.45 microU/ml, p < 0.01). A thyrotropin-releasing hormone (TRH) test was performed in 10 women having the highest TSH levels. All the results of TRH tests were consistent with occult hypothyroidism. These women were treated with L-thyroxine and all had a significant improvement in their bleeding within 3 months of treatment. We concluded that any IUD-wearing woman suffering from menorrhagia may have occult hypothyroidism. Should FT and TSH be within normal limits, a TRH test should be performed as the definitive diagnostic test. A frequent side-effect of intrauterine contraception is menometrorrhagia. The intrauterine device (IUD) has to be removed in 5-15% of cases to prevent iron deficiency anemia. PMID- 1290334 TI - A multicenter clinical trial in Nigeria with Multiload-Cu250 (MLCu250) and Multiload-Cu375 (MLCu375) intrauterine devices. AB - A multicenter study was conducted in Nigeria, comparing the Multiload-Cu250 (MLCu250) with the Multiload-Cu375 (MLCu375). The two intrauterine devices were studied on aspects of effectiveness and acceptability. Parameters were observed and analyzed, using the life-table method of Tietze and Lewit. Continuation rates were excellent. Overall results were in line with studies done elsewhere in the world with Multiload devices, showing a slight superiority of the MLCu375 over the MLCu250. PMID- 1290335 TI - Early pregnancy termination: an improved technique for 'menstrual regulation' with ultrasound assistance. AB - We performed aspiration of early pregnancy on 100 women requesting termination, using a low caliber angled catheter under sonographic guidance, without analgesia or anesthesia. The sonographic inclusion criteria for the study were: (1) mean gestational sac diameter less than 30 mm, or (2) crown rump length less than 10 mm when an embryo was visualized. The uterine content was successfully evacuated in all cases and none needed an additional curettage. Two women developed mild endometritis which responded to antibiotic therapy. This refinement of this 'menstrual regulation' technique seems to be safer when compared with the reported results of the original technique. PMID- 1290336 TI - Interrupted extra-ovular infusion may not be reversible. AB - Late abortion ensued 9 days after discontinuation of extra-ovular PGE2 infusion for mid-trimester termination of pregnancy in a 15-year-old unmarried primigravida. This observation, which has no precedent in the literature, may suggest that once extra-ovular PG infusion has been started, its discontinuation may not be considered reversible. PMID- 1290338 TI - Recovery from brain damage. Neuropsychological rehabilitation. PMID- 1290339 TI - Hemidecortication and recovery of function: animal studies. PMID- 1290337 TI - Recovery from brain damage. Reflections and directions. European Brain and Behaviour Society's Workshop on Recovery of Function Following Brain Damage. London, April 1991. Invited review lectures. PMID- 1290340 TI - A review of cognitive outcome after hemidecortication in humans. AB - This review of the effects of hemidecortication in humans has been limited to studies of cognitive outcome published during the last 20 years. More directly than in the case of split-brain patients, the patients reviewed here attest to the remarkable ability of a single hemisphere, whether left or right, to support at least at modest levels a wide range of cognitive functions--from visual perception, through memory and intellectual processes, to language and even speech. In some cases, as has been indicated, the surgical removal of a diseased hemisphere has resulted in improvement of cognitive function. This positive outcome has occurred more frequently in patients with early (i.e. congenital or perinatal) onset of seizure disorders than in those with late onset (e.g. Rasmussen's disease). But even for the latter patients, the cognitive costs of the surgery per se have rarely been severe. And in both types of case, the incidence of either complete or substantial postoperative relief from intractable seizures has been high, ranging around 80-90%. Although the therapeutic efficacy and small cognitive costs of the surgery are now quite well established, little is known yet regarding the specific cognitive defects that arise from the loss of one as opposed to the other cerebral hemisphere. Intelligence levels have been found to be equally low, averaging in the mid-60s and almost never rising above 100 in patients with either left or right hemidecortications, and memory quotients have most often appeared to fall in line with the IQ scores, again without clear evidence of any difference in the effects of left and right removals. Even in the case of visual spatial perception, considered to be a hallmark of right hemisphere function, the evidence is unclear, one study reporting selective impairment on difficult visuospatial tasks in right hemispherectomised patients, but another not. Only in regard to language processes is there a consensus regarding the differential effects of left and right hemidecortication, and here the differences are apparent only in the relatively subtler aspects of language. Thus, the isolated right hemisphere is at a significant disadvantage compared with the left in the comprehension of abstract, low frequency words, in phonetic feature analysis, and in the subtleties of grammar, such as the comprehension of passive negative constructions and the correct use of morphological markers in unfamiliar contexts (e.g. application of comparative and superlative forms of an adjective to nonwords.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1290341 TI - Mechanisms underlying recovery from cortical injury: reflections on progress and directions for the future. PMID- 1290342 TI - Recovery from brain damage. Research on recovery: ends and means. PMID- 1290343 TI - Recovery from brain damage. Recovery of function: nutritional factors. PMID- 1290344 TI - Environmental approaches to recovery of function from brain damage: a review of animal studies (1981 to 1991). PMID- 1290345 TI - 1992 Guide. Nursing career opportunities. PMID- 1290346 TI - [Mathematical model of oblique three-dimensional intertrochanteric detorsion varus-forming osteotomy of the femur by the Bernbeck method in surgical treatment of congenital hip dysplasia in children]. AB - Whenever the conservative procedure fails to bring about congruence of the dysplastic hip joint, an operative procedure becomes indispensable. In Orthopaedic Clinic of the Pomeranian Medical Academy in Szczecin we implement the oblique three-dimensional intertrochanteric detorsion and varus forming osteotomy after Bernbeck in order to correct the proximal end of the femoral bone. Precise determination of the plane to be cut, prior to the operative procedure, simplifies and shortens the operation itself and facilitates the achieving of the planned angular values in all three planes. Mathematical model of osteotomy according to Bernbeck considering required angles of correction as well as angles determining the plane of osteotomy was worked out. In collaboration of the Szczecin Technical University, a simple computer program was elaborated which allowed the presentation of the results in the form of tables. With the help of tables the optimal cutting plane was chosen and created correct biomechanical and anatomical conditions as well as optimal conditions for stable osteosynthesis of dissected fragments of the femoral bone. That type of osteotomy is useful in most operative correcrions of the dysplastic hip joint (not great varus formation connected with relatively extensive detorsion). The achieved congruence in the 22 dysplastic hip joints operated on was the most important condition for their later physiological development. Short post-operative observations confirm the value of described mathematic model. PMID- 1290347 TI - [Control of the quality of radioimmunological methods of determining plasma levels of atrial natriuretic peptide (ANP) and the evaluation of their usefulness in clinical studies]. AB - The radioimmunologic assays appeared to be the most convenient methods for determination of atrial natriuretic peptide (ANP) concentration in blood plasma. The purpose of this work was to compare the control quality parameters of two radioimmunologic methods for the ANP determination in human plasma: the methods described by Pruszczynski et al. and the method with the use of Amersham ready made set (kit). The comparison of the two methods was performed by analyzing 10 series of ANP determinations carried out by Pruszczynski method, and 15 series by means of the kit. Both methods appeared to fulfil the criteria of satisfactory quality for RIA determinations. The second purpose of this study was to define the utility of the RIA method for the determination of ANP in clinical practice, taking into the consideration some factors influencing or modifying plasma ANP levels. Three groups of persons of were studied: 15 healthy subjects, 16 patients with acromegaly and 47 patients with the impairment of renal function. The ANP level in plasma was determined in these 3 groups of persons. It has been demonstrated that the change of body position from upright to supine caused the increase of the ANP concentration in plasma. It has also been found that the decrease in the intravascular fluid volume induced by furosemide administration resulted in the reduction of ANP concentration in plasma. The enlarged intravascular fluid volume, accompanying acromegaly and probably present in persons with the impairment of kidneys, was associated with the increased ANP concentrations in plasma. PMID- 1290348 TI - [Evaluation of immunological studies in patients with rheumatoid arthritis]. AB - Immunological studies are widely applicable at a clinic in rheumatoid patients, despite the fact that their clinical value is still a disputable subject. Many authors are of opinion that the determination of individual immunological tests does not provide the estimation of immunological state in patients, and should be evaluated critically. The aim of the actual paper was to evaluate the immunological state of patients with rheumatoid arthritis by means of immunological profile index, which consists in performing concurrently many immunological tests involving both humoral immunology and cellular one. The results were referred to the duration of the disease, pathological process activity, the presence of rheumatoid factor, the advancement of osseous changes. The studies were carried out in patients, aged 16-69 years, 63 of them had RA and 9 were affected by ankylosing spondylitis. The control group comprised 16 normal subjects aged 28-61 years. It has been disclosed that the values of the immunological profile index in patients were statistically significantly lower than in the control group. The lowest values of immunological profile index were recorded in patients with extra-articular symptoms with recurrent infections of urinary and respiratory tracts, as well as in patients with active form of RA, and the presence of rheumatois factor. The patients with ankylosing spondylitis were found to reveal immunological disorders, but they were expressed less markedly than in RA patients. With the help of immunological profile it was possible to show that multifunctional immunological disorders appeared in patients with rheumatoid arthritis. The most sensitive immunological tests were: levels of immunoglobulins in blood serum, and the count of lymphocytes T and B. The immunological profile study in patients with rheumatoid inflammation of joints is an objective method of evaluating their immunological state. PMID- 1290349 TI - [Electrophysiological characteristics of the heart with special reference to the sinoatrial node function in patients with disorders of the atrioventricular and intraventricular conduction]. AB - Sinus node function and other electrophysiologic properties of the heart in patients with atrioventricular or intraventricular blocks are not well documented. I therefore performed electrophysiological studies in 35 patients with chronic high degree atrioventricular block (AVB--group I), 20 patients with bifascicular block (BFB--group II) and in 24 control subjects (group III). Multilevel conduction disturbances were found in 51.5% of patients with AVB and in only 10% of patients with BFB. Sinus node dysfunction was disclosed in 3 patients (8.6%) with AVB (in 1 it was functional) and in 3 patients (15%) with BFB. A new modified method for recording sinus node electrogram (SNE) was described. By applying this method, SNE was recorded successfully in 80% of cases. The results are comparable to those of other methods. Retrograde conduction was observed in 34% of patients with AVB, 75% of patients with BFB and in 38% of control subjects. It plays an important role in the pathogenesis of the "pacemaker syndrome" in patients with VVI pacemakers. Atrial hyperexcitability was observed in 5.7% of patients in gr. I, 10% in gr. II and 4.2% in control group only. Rare occurrence of atrial arrhythmias provoked by electrical stimulation provides the possibility to use DDD or VDD pacing systems in patients with AVB or BFB. Inadequate rate of response to exercise (chronotropic incompetence) was observed in most patients with sinus node dysfunction, but it occurred also in patients with normal sinus function. CONCLUSIONS: 1) Sinus node dysfunction is uncommon in patients with atrioventricular or intraventricular blocks. 2) Persistence of abnormal sinus node function and atrioventricular or intraventricular conduction disturbances after autonomic inhibition is an argument for organic disseminated injury of the conduction system (binodal disease). 3) Electrophysiological evaluation of sinus node function, retrograde conduction, artial hyperexcitability and chronotropic response to exercise permit suitable choice of physiological pacing mode (VDD, DDD, DDR, VVIR) in patients with AVB or BFB. PMID- 1290350 TI - [Analysis of disorders of adolescent behavior at the Diagnostic- Referral Family Center in Szczecin]. AB - As many as 120 subjects, directed in 1984-1988 to the Diagnostic-Consultative Family Centre in Szczecin, were studied due to behaviour disorders or penal acts. Thirteen (10.8%) juveniles were exempted from further studies, since they were diagnosed to have mental deficiency or encephalopathy. The rest was studied by means of diagnostic criteria for behaviour disorders according to DSM-III-R. Those complying with the criteria made up a group with Behaviour Distemper Syndrome (BDS)--74 persons (55 boys and 19 girls), while the others formed a group holding Single Behaviour Distemper (SBD)--33 persons (21 boys and 12 girls). Two age subgroups, 7-14 and 15-17 years, were isolated from each of the groups. Use was made of own questionnaire to collect data concerning factors that might induce the revealed behaviour disorders. Groups BDS and SBD were compared with regard to the type and incidence rate of respective signs of behaviour disorders, according to criteria DSM-III-R, and also the age, sex as well as social background, living environment, and hereditary encumberance, course of pregnancy and delivery, former psychophysical development, use of condiments, somatic disorders actually evidenced, parental and school environmental atmosphere and that of peers of the studied group. PMID- 1290351 TI - [Evaluation of temporo-mandibular myoarthropathies, the status of the masticatory system and patients' personality based on the tests and clinical studies]. AB - Resorting to commonly applied methods and clinical indices, the masticatory organ state was evaluated in 64 patients with symptoms of myoarthropathy (studied group)) and in 61 patients without the symptoms of the disease (control group). The assumption laid down in the work was that the studied group and the control one do differ with regard to the incidence rate and the intensity of the investigated local parameters and the level of neuroticism as well as extraversion. The aim of the paper was to show the mutual correlation between the parameters studied, and to determine their effect on the inception of the temporal jaw dysfunction. It has been revealed that the advancement of age is accompanied by statistically significant increase in the incidence rate and intensity of local diseases as well as by malfunctions, a rise in the level of neuroticism and a drop of the extraversion level. In consequence of the former findings, severe forms of dysfunction of the mandibular articulation arose in 89% of patients within the highest age group. Comparing the parameters between the studied group and the controls provided the possibility to isolate the features that make the both groups differ, thus facilitating the determination of the influence the individual factors exert on the origination of dysfunction of the mandibular articulation. The most essential differences affected five factors: unilateral mode of mastication, parafunction, teeth deficit, abnormal occlusion and high neuroticism. The lack of statistically significant differences between the studied and control groups with respect to periodontal diseases, looseness of teeth, dental abrasion do not authorize us to exclude their influence on the formation of temporal jaw myoarthropathy, since these factors are responsible for the loss of teeth, occlusal articulation disorders, and in an indirect way they, undoubtedly, exert destructive influence on the organ of mastication. PMID- 1290352 TI - [Selected etiological factors in dental caries among 18-year-old high-school students in Poland in the light of the results of the questionnaire and epidemiological studies]. AB - The performed studies covered 1100 subjects being 18 years old (both girls and boys) representing large and small towns as well as villages situated in 13 provinces. The material and methods were based on the instruction provided by "WHO Basic Methods 1986". Answers given to questionnaire inquiries in the area of nutrition and oral cavity hygiene furnished an image of health consciousness and behaviours of 18-agers in Poland. Dental state and stomatologic treatment requirement jointly with the effects of stomatologic care were evaluated on the basis of the results established by epidemiological studies. The accomplished analysis encompassed the influence of sex, living environment, type of schools and variable content of fluoride in water, exerted on the pattern of the investigated epidemiological parameters. No correlation was recorded between health consciousness and behaviours in 18-year-old youth on the one hand, and the dental state as well as the therapeutic requirements on the other. The questionnaire responses and the epidemiologic studies made it possible to disclose some drawbacks in transmitting and introducing the education-health principles, which was reflected by not the best results concerning the health consciousness and behaviours particularly in male youth and in rural inhabitants. The dental condition is unsatisfactory in the studied population, despite being provided, in most instances, with permanent stomatological care. This indicates that optimization of adequate stomatological service is indispensable. A low percentage of youth with dentition does not predict good prognosis for them to achieve 3-rd health objective set up by WHO for the year 2000. The studies have confirmed the influence of big urban environment, with complete profile of stomatological care and water fluoridation, being exerted on the state of dental therapeutic requirements in 18-year-old youth. Difficult as it appeared was the detection of the sugars consumption role and that of oral cavity hygiene, in the course of one-stage investigation. PMID- 1290353 TI - [Molecular-genetic evaluation of translocation of bcl-2 gene and locus bcl-1 in selected lymphoproliferative changes]. AB - In the work it has been decided to evaluate the occurrence of locus bcl-1 rearrangement in type B chronic lymphatic leukemia and that of gene bcl-2 in non Hodgkin's lymphoma with diffuse morphology, as well as in reactive lymph nodes. The study material comprised DNA isolated from fragments of lymph nodes sent for routine diagnostic examinations at the Institute of Pathology--Pomeranian Medical Academy. Southern's method was used to examine DNA having been cut with restrictive enzymes, estimating the distribution of gene bcl-2 and locus bcl-1. Resorting to Polymerase Chain Reaction (PCR) translocation t (14;18) was assessed by means of short nucleotides hybridizing with 14 and 18 chromosome sequences restricting this translocation. The amplification product was subsequently studied by Southern's method with probe bcl-2. In 1 out of 18 examined cases of type B chronic lymphocyte leukemia it was disclosed that locus bcl-1 had been rearranged. In 45 cases of non-Hodgkin's lymphoma with diffuse morphology the gen bcl-2 was found to display germline arrangement. Germline position of gen bcl-2 was also revealed in 60 cases of reactive lymph nodes. PMID- 1290354 TI - [Serum C-reactive protein monitoring in children after injuries of closed body cavities]. AB - Serum CRP-level monitoring was performed in 101 children after trauma of occlude body cavities to determine its applicability in diagnostic procedure, treatment and prognosis. Case history of a patient, clinical status, type and course of treatment provide the basis for establishing clinical punctation in each group of injury for statistical purposes. As many as 87 children with head trauma, 5 having abdominal trauma, 8 with traumatized heads and abdomens, and 1 with chest injury were investigated. All the studied groups revealed similar graph of CRP levels. Until the third day after injury, dynamic rise was being observed followed by slower elimination phase proceeding to the initial level on the seventh day after the injury. Dynamics of CRP outputs and their positive correlation with the area under the curve in all groups investigated shows that CRP monitoring is useful for clinical purpose. PMID- 1290355 TI - [Effect of pollen extract (Cernitin) on the course of poisoning with organic solvents (biochemical analysis)]. AB - The aim of the study has been to experimentally estimate the chronic exposure of selected biochemical parameters of serum and microsomal level fraction in animals to a mixture of organic solvents. An attempt was made to alleviate the eventual changes by applying Cernitin preparation. The experiment was performed on male rats, Wistar strain. The rats were exposed to the organic solvents in a toxicological chamber with controlled parameters. Cernitin preparation was added to standard diet, being given to the animals in the form of balls. The biochemical investigations were carried out after a lapse of 3 and 6 month exposition. The range of the accomplished studies included: activity of enzymes (AspAT, AlAT, AP, ChE) bilirubin level and lipids content in blood serum. Lipids content was determined in liver homogenate. The content of protein, cholesterol, phospholipids and free fatty acids, was studied in liver microsomes. It has been shown that protracted exposure to the mixture of organic solvents elicits an increase in the activity of the studied aminotransferases and alkaline++ phosphatase, as well as a decrease in the activity of cholesterase. The changes in activity are accompanied by a rise in the content of lipids. Cernitin preparation used prophylactically normalizes impairments affecting the studied enzymatic and lipid parameters. PMID- 1290356 TI - [Biomechanical aspects of surgical treatment of secondary stenosis of the spinal canal in the lumbosacral region]. AB - In experimental studies and on clinical material, behaviour was checked of intervertebral discs and vertebrae under the axial pressure: which is the being exerted by the trunk weight, as well as the behaviour of the adjacent mobile segments after "diskoplasty" operation or vertebral interbody stiffening. The material pertaining to the experimental part comprises 6 undamaged spine preparations of the lumbosacral segment, while the clinical part consists of 60 patients out of 143 subjects having been operated on by "diskoplasty" or vertebral interbody stiffening from the approach through fenestration, hemilaminectomy, or plastic laminectomy. The results of performed experimental studies and spodylometric analysis of radiograms in patients treated operatively by decompressing the vertebral canal and by "diskoplastic" stabilization of the vertebrae, or vertebral interbody stiffening permit the following observations. The most favourable localization of the transplant is the medial and posterior parts of the vertebral interbody space, since in both segments L4/L5 and L3/L4 it reproduces the height of the vertebral interbody space, the height and width of intervertebral foramen, widens the intervertebral foraminis, and reduces the lumbar lordosis, which advantageously changes the biomechanic relations, transferring loads of the posterior to the anterior vertebral column. The localization of the transplant in the anterior part of the vertebral interbody space, in fact, increases the anterior vertebral interbody space, but decreases the height of posterior interbody space, the vertebral interbody angle alpha as well as the height and width of the intervertebral foramen. The retroshifting of vertebral L4 indicates mobile segment instability. By implementing a transplant of matching height and appropriate localization in vertebral interbody space, it is possible to increase or reduce the angle between the vertebral bodies at the operative level, widening the vertebral interbody space in anterior and posterior parts. The localization of the bony transplant in the anterior part of vertebral interbody space, involving the clinical material, caused in 65% constriction of intervertebral foraminis, retroshifting of vertebrae L4 and L3, and recurrence of algesic complaints, which may be elucidated by instability of the operated on or adjacent mobile segments. PMID- 1290357 TI - [Gastrinoma: epidemiology, general findings, and anatomopathologic aspects]. PMID- 1290358 TI - [Gastrinoma: clinical and instrumental diagnosis]. PMID- 1290359 TI - [Therapeutic strategy for gastrinoma]. PMID- 1290360 TI - [Current approaches in the treatment of gastrinoma metastases]. AB - In the last years the therapeutic behaviour with regard to gastrinomas, has deeply changed becoming more and more aggressive. Nowadays, almost all authors recommend, after a serious treatment of the hypersecretion with omeprazole, an explorative laparatomy in all patients affected by gastrinoma even without a preoperative tumor localization. The multiple endocrine syndrome (MEN I) and the metastatic disease are excluded from the above practice. A careful examination of the most recent data available today in literature accompanied with our experience, even if limited, shows that only the surgical treatment allows a better survival also in metastatic disease. The surgical treatment is surely recommended in gastrinoma with pancreatic and duodenal lynphonodal metastasis. For hepatic metastasis all types of hepatic resection, the "wedge resection" included, can be suggested. After the first positive experiences, the hepatic transplantation can find a place among the therapeutic means against this kind of tumors. PMID- 1290361 TI - [Antonio Pacchioni (1665-1726): pioneer studies on the dura mater]. AB - Clustering of arachnoid villi along the sagittal sinus gives rise to the so called "Pacchionian Granulations". These structures were originally described in 1705 by Antonio Pacchioni, an Italian scientist. Born in Reggio Emilia in 1665, he graduated in Medicine in his hometown and later moved to Rome were he built up a successful career by dedicating to medical practice as well as to research and teaching. He became friend and often collaborated with some of the leading scientists of his age: Lancisi, Malpighi and Morgagni among the others. Moreover he carefully followed research developments in Europe as testified by frequent quoting of foreign authors in his works. He devoted himself to the elucidation of structure and function of Dura Mater, often by using new techniques of maceration of anatomic specimens in various fluids. Among Pacchioni's works, the "Dissertatio epistolaris de glandulis conglobatis Durae Meningis humanae" (1705) is particularly well known and contains the first description of arachnoidal granulations. He compared Dura to cardiac muscle and attributed to its "glandulae" (glands) the faculty of secreting lymph for lubrification of the sliding movements between meninges and brain during contractions. He died in Rome in 1726. Three centuries after Pacchioni's death fine structure of arachnoid villi hasn't been fully elucidated; moreover many questions on mechanisms underlying CSF absorption remain unanswered. PMID- 1290362 TI - [Heart complications in general surgery: results of a multicenter study]. AB - Cardiac events are the most dangerous postoperative complications since they may be easily followed by the death of the patient. The related risk factors were prospectively evaluated in a study of 1182 patients. Stepwise regression logistic model was employed for statistical analysis. Preoperative cardiac and respiratory failure, ventricular arrhytmias, compromission of the nutritional status, presence of neoplastic disease and prolonged anesthesia over two hours were the only significative factors related to postoperative cardiac complications. Advanced age was not a major risk factor. The results of the study require a prospective validation. They are however comparable to those observed in the literature Preoperative cardiac evaluation is of utmost importance for cardiac prognosis and various instrumental, sometimes invasive diagnostic procedures have been proposed. The Authors provide a usefull, simple and widely employable system of general and cardiac assessment for the determination of cardiac risk. PMID- 1290363 TI - [Therapeutic problems in euthyroid multinodular goiter]. AB - Now therapeutic different possibilities of goitre pathology seem well defined, in front of limit of suppressive therapeutic range in initial stages, prevalently diffuse, that interest young people and arise in jodic want lands; it's possible that medic theraphy ends can't be obtained because of not responders patient, or even for possibilities of controindications. Local presence of suspicious nodules and the need of goitre volumetric reduction for aesthetical and compressory ends, with the possibility in course of time of functional changes are sure reasons to surgery. Certainly main problems exist about surgery definition of multinodular disease with bilobar involvement where there is comparing between total and subtotal thyroid exeresis. Now by literature analysis and our School experience we think that surgery choice, considered before operation, must find absolute assurance after preoperative morphotopographic careful exploration of thyroid. We think that total thyroidectomy must be done when it's certain a total gland involvement, reserving subtotal thyroidectomy in the other cases; always employing a careful surgery technique, keeping operative field interely bloodless to identify important structures and dissection plan narrowly close by capsule. PMID- 1290364 TI - [Ectopic parathyroid glands in primary hyperparathyroidism]. AB - The incidence of the ectopic parathyroid glands seems to be different between normal subjects and patients affected by primary hyperparathyroidism. We reviewed a serie of patients operated on for primary hyperparathyroidism in our Institute between 1985 and 1991, and the reports from literature about this mean; the frequence of ectopies is = 31% (10.3% in the upper- anterior mediastinum). These findings are similar to those reported in the literature. The higher incidence of ectopies in the hyperparathyroid group respect to the normal one and the surgical problems that it could cause represent a reinforcement of the concept that parathyroid surgery should be done only by an experienced, technically and theoretically prepared surgeon, and may justify the use of non invasive, non expensive imaging techniques at the first cervical exploration for suspected hyperparathyroidism, in order to ameliorate the results and in particular to solve suddenly some dramatical cases due to major parathyroid ectopies. PMID- 1290365 TI - [Esophago-gastric lesions caused by caustics]. AB - A wide range of lesions may occurs after accidental or voluntary ingestion of caustic substances including mild epithelial injury to whole thickness necrosis of the involved organs. The type of management varies according to the severity of the damage, medical therapy being indicated in the less severe cases while surgery is required in life threatering lesins or alternatively as elective treatment of trighly desabling sequelae last complications such as. From 1981 to 1989 we observed 20 patients with acute hastro-oesophageal lesions due to ingestion caustic substances 19 of then were successfully treated with medical therapy. Only 1 patient underwent surgery and died of oesophagus cardiac fistula with right atrium perforation (24 days following total gastrectomy). Based on either our own experience and the data reported in the literature we believe that the most adequate management of patients with lesions of the E.G. due to caustic agents tract must include: vital functions control maintenance intensive care treatment of shock endoscopic monitoring of E.G. lesions emergency surgical treatment where needed. PMID- 1290366 TI - [Our experience with early gastric cancer]. AB - Authors assert that, in Early gastric cancer diagnosis, anatomicomedical characteristics expressed on the basis of canons formulated by Endoscopy Japanese Society and by Lauren's unexipered classification are of particular interest. After having referred on characteristics observed on a group of patients, in the light of data given from medical Literature, they try to extrapolate aetiopathogenetic factors. These, together with anatomicopathological characteristics of the lesion, are the premises for a wise radical therapeutic choice. PMID- 1290367 TI - [Anatomo-clinical considerations on early gastric cancer]. AB - After having asserted the still rising interest for an as early as possible diagnosis of gastric cancer, authors refer on a group of patients who are carriers of Early gastric cancer. After having touched upon localization and histological characteristics of neoplasms, linger on the rules that leaded their therapeutic choice and they report the results of a follow-up dragged ten years long. They terminate affirming only a timeliness diagnosis can consent a really decisive therapeutic approach. PMID- 1290368 TI - [The finger fracture technique in hepatic resection]. AB - The main complementary techniques for "finger fracture" in liver resections are evaluated. It is retained that transparenchymal resections should be limited to segmental resections (uni-, bi- or trisegmentectomies), while in case of extensive resections (lobectomy or extensive lobectomy) an operation with extraparenchymal preparation of the hepatic pedicle and possibly of the suprahepatic vein is preferable. Lastly a casuistry of 24 hepatic resections for primary or metastatic tumours is presented. PMID- 1290369 TI - [Spontaneous perforations of the large intestine]. AB - Spontaneous perforation of colon is a rare disease and physiopathologic basis are actually unknown. Surgical treatment is standardized and post-operative survival is over 60%, morbidity and mortality rate depends on peritoneal contamination. In 1984 J.A. Berry classified spontaneous perforations into "stercoral" and "idiopathic" perforations on the basis of etiopathogenetical causes of lesions. Anatomopathologically stercoral and idiopathic perforations present different characteristics. Macroscopically stercoral perforation origines from an ulcerative lesion often situated on the sigmoid colon or rectum. Microscopical characteristic is represented by a superficial ischemic necrosis of mucosa (caused by fecalomas) followed by an extension to sub-mucosa and muscular tissues of the colonic wall. On the contrary, "idiopathic perforation", frequently situated on the sigma, is a linear laceration of anti-mesenteric side of the colon without pathologic modifications of the colon. Physiopathologic basis of spontaneous perforations of the colon were also discussed. Stercoral perforation is often a consequence of chronic constipation. Instead, two hypoteses are advanced as regards idiopathic perforations. S.V. Kessing e coll. (1962) hypotized a parietal suffering caused by ischemia of anti-mesenteric side of the colon, depending on ipoperfusion of colonic tissues; they also hypotized a constitutional weakness of colonic wall as a cause of idiopathic perforation. Others hypotized an intraluminal hypertension caused by intestinal hernias (J.W. Eadie, 1955; K. Cronin, 1959), rectal prolapse or abnormal depth of Douglas cavity (D.C. Lyon, 1969). In these cases, lesion is caused by contraction of abdominal muscles during defecation, which presses colonic wall during distension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290371 TI - [Carcinoid neoplasms: report of 5 personal cases]. AB - The authors report 5 cases of carcinoid tumor differently located. The typical carcinoid syndrome has been observed only in one case, presenting with high levels of urinary serotonin and 5-OH-HIAA. The remnant patients were completely asymptomatic and the correct diagnosis was obtained only by histologic examination of the surgical specimen. On the basis of their experience and of the literature, the authors evaluate the current diagnostic and therapeutic options for these neoplasms. The indication for surgical treatment, even in cases with local or distant metastases, is emphasized. PMID- 1290370 TI - [Treatment of postoperative entero-cutaneous fistula: personal experience]. AB - The authors present their experience on surgical treatment of intestinal fistulas based on personal cases treated from 1981 to 1990. The cases are divided into two groups: the first: the first group of patients was treated only surgically (1981 1984); the second group was treated with surgery and artificial nutrition (1984 1990). The mortality rates are much lower in the second group. The conclusion is that is always necessary to associate a form of artificial nutrition to surgery because the percentage of healing is statistically higher. PMID- 1290372 TI - [Comparison of color duplex and phlebography in the diagnosis of deep venous thrombosis of the legs]. AB - The aim of this prospective study was to evaluate the efficacy of color duplex scanning in comparison with plebography in patients with clinically suspected deep vein thrombosis of the legs. The group was of sixty patients. The tests were both positive in 51 limbs and negative in 8 limbs. In a case of below-knee thrombosis, color-duplex was negative while phlebography was able to show small localized thrombosis. The sensitivity of color-duplex was 98%, its specificity and positive predictive value 100% and its negative predictive value 88.8%. In conclusion, color-duplex is as effective as phlebography in detecting deep vein thrombosis above knee. PMID- 1290373 TI - Bibliographic information retrieval. PMID- 1290374 TI - [Biological cycle of Paralibyostrongylus hebrenicutus (Nematoda: Trichostrongylidae)]. AB - Paralibyostrongylus hebrenicutus accomplishes its life cycle spontaneously in captive Atherurus africanus, its natural host, and in experimentally infected guinea pigs and rabbits. Morphogenesis and larval morphology were studied in the guinea pig and described herein. Host infection were achieved either by subcutaneous or by oral inoculation. The entsheathed infective larvae moult soon after penetration in the vertebrate host. Following subcutaneous inoculation, they reach the lungs very probably through the lymphatic vessels and the right heart at H8, and the stomach as soon as D2. However, a possible direct migration by the mesenteric lymphatic vessels and crossing of the digestive wall cannot be excluded as a few larvae were found in the peristomachal mesentery. Following ingestion, L3 larvae reached the stomach directly. 24 hours post-ingestion, they were localized deep inside the gastric mucosa crypts lumen. The same larval localization was observed at D3 after a subcutaneous inoculation. At D5, regardless of the inoculation route, larvae reached their definitive position, embedded in the gastric mucosa mucus lining, where they underwent the 3rd moulting (L3-L4) followed by the 4th moulting (L4-Ad) at D19. Eggs appeared at D28. Except for the inflammatory granuloma seen in the lungs and the mesentery from H24 to D3, the nematode induced no tissue lesion. The genus Paralibyostrongylus is one of the most primitive in the Libyostrongylinae Cooperiinae line. The double transmission route, may have made possible the transition from primitive cycles by cutaneous penetration to more specialized cycles by the oral route, the latter being responsible for the evolutionary success of the group in large herbivores. PMID- 1290375 TI - An account of the ticks of the northeastern of Spain (Acarina: Ixodidae). AB - The tick species commonly collected at the Northeast of Spain are reported in this paper. Data on hosts, temperature and humidity requirements, vegetation relationships, altitudinal distribution, and seasonal activity are included. R. sanguineus is commonly collected in areas with Mediterranean vegetation, esteppe, and semi-desertic esteppe, ranging from 190 to 1,000 meters above the sea level. R. sanguineus is related with sparse vegetal areas, and it is absent from areas with dense shrub or forests of every kind; sometimes, small populations may be collected in ecotones between Pinus spp. and esteppe formations. R. pusillus is closely related to areas of Mesomediterranean vegetation, sometimes subordinate to Pinus spp. and Quercus spp. The climate to which the species ally is always of continental type, with a hot and dry summer, and cold winter; although the species is commonly restricted to its main host, Oryctolagus cuniculus, several specimens have been collected from V. vulpes. Our data display the clear affinity of I. ricinus to the Supramediterranean vegetation (Aceri-Quercion faginae), places of Quercetum-Buxetum, as well as the Iberian Oromediterranean vegetation (Pinus sylvestris-Buxus sempervirens). Captures are scarce in forest of Fagus sylvatica, but data suggest that the species may be locally common on such places. Climate for the zones of collection of I. ricinus is Atlantic attenuated, with mild summers and humid winters. D. marginatus is strongly related to the xerophilic vegetation, widely spread through the Mediterranean, Supramediterranean, and hill levels, but does not colonize the true Oromediterranean vegetation. In our captures, the species is commonly collected in pubescent oak formations, but it does not penetrate in true forest associations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290376 TI - Vaccination of cattle against Rhipicephalus appendiculatus with detergent solubilized tick tissue proteins and purified 20 kDa protein. AB - Three groups of 4 cattle have been vaccinated with either detergent solubilized tick tissue proteins (SMP) of male and female Rhipicephalus appendiculatus, a 20 kDa soluble integumental antigen, a mixture of both SMP and 20 kDa. Two weeks after one booster injection all cattle were challenged by infestation with adult ticks. Treatment had no influence on tick attachment but on cattle vaccinated by the 20 kDa 32.5% fed ticks died (p < 0.001). Moreover, the mean weight of ticks fed on 7 out of 12 vaccinated cattle was significantly lower (p < 0.05 to p < 0.001). Individual differences could be seen where the mean weight reduction was up to 30%. Moreover, ticks fed on 1 (group SMP) or 2 cattle (group 20 kDa) had some difficulties in converting their blood meal into eggs (p < 0.05 to p < 0.001). PMID- 1290377 TI - [Leishmania major MON-117, an agent of cutaneous leishmaniasis in Mauritania]. AB - The causative agent of cutaneous leishmaniasis in Mauritania is identified for the first time as Leishmania major MON-117, a new zymodeme closely related to MON 26. The authors point out the need to study this previously unknown focus. PMID- 1290378 TI - Larval stages of medically important flukes (Trematoda) from Vientiane province, Laos. Part II. Cercariae. AB - The cercariae of five flukes, which are potential human parasites, Opisthorchis viverrini (family Opisthorchiidae), Haplorchis taichui (Heterophyidae), Schistosoma spindale (Schistosomatidae), Fasciolopsis buski, and Fasciola gigantica (Fasciolidae) were found in freshwater snails from Laos. The cercariae of the above species, recorded in Laos for the first time, are illustrated and their morphology is briefly described. The snail Helicorbis umbilicalis represents a new intermediate host of F. buski. The occurrence of medically important snails in the Vientiane province will also be discussed. PMID- 1290379 TI - Study on the surface morphology of the developmental stages of the liver fluke, Opisthorchis viverrini (Trematoda: Opisthorchiidae). AB - The external morphology of some developmental stages of the fluke Opisthorchis viverrini (Trematoda: Opisthorchiidae), parasitizing humans in Southeast Asia was studied for the first time using electron microscopy. The surface structure of the egg, as well as the rediae, cercaria, metacercaria, and adult found in naturally infected hosts from Laos are described herein and their morphological characteristics discussed. PMID- 1290380 TI - Haemaphysalis juxtakochi, Ixodes pararicinus (Ixodidae) and Otobius megnini (Argasidae) in relation to the phytogeography of Argentina. AB - The phytogeographical distributions of Haemaphysalis juxtakochi, Ixodes pararicinus and Otobius megnini in Argentina are described from material collected mainly from 1978 to the present. H. juxtakochi was found in the northwestern area of the Amazonian domain and in the Chaco, Espinal and Pampean provinces of the Chaco domain. It was detected on Mazama spp., Tapirus terrestris, dog, cattle and on the vegetation. Most findings of I. pararicinus were from mountain rangeland, where it was found on cattle and in a lesser extent on horses. Ticks from Argentina classified as Ixodes ricinus were probably I. pararicinus. O. megnini was detected on cattle an sheep in the Andean Patagonian domain and in the Monte, Chaco and Espinal provinces of the Chaco domain. This tick is considered typical of arid and semiarid conditions, however the findings from the Espinal province where from areas with an annual rainfall over 900 mm. PMID- 1290381 TI - Angiostrongylus costaricensis natural infection in Vaginulus plebeius in Nicaragua. AB - A study of 94 slugs, collected from urban and rural areas in and around Leon, Nicaragua, was carried out in order to confirm the role of Vaginulus plebeius as an intermediate host of Angiostronglylus costaricensis. Third-stage larvae of A. costaricensis were obtained from these molluscs. Some of these larvae were then orally inoculated into two laboratory-bred rats Sigmodon hispidus and adult worms of A. costaricensis were recovered two months later. The infection rate of these slugs ranged from 4% in urban areas to 85% in rural areas. These data suggest that contamination to man is a major risk especially in rural areas and that abdominal angiostrongyliasis could be a health problem in Nicaragua. PMID- 1290382 TI - [Thrombosis and thrombin]. AB - Thrombosis, either venous and arterial, is the most important cause of death in our society. Thrombin formation is a pivotal step in the pathogenesis of both forms of thrombosis. Drugs like heparin and vitamin K antagonists act because they inhibit thrombin formation. Better drugs than conventional heparin and oral anticoagulants are however urgently needed. They can be found on basis of a better understanding of thrombin formation. The mechanism of thrombin formation is explained. The mode in which conventional heparin and the newer, low molecular weight heparins inhibit this process is discussed. It is shown that, contrary to current belief, low molecular weight heparins inhibit primarily via their action on thrombin and that the inhibition of factor Xa is of less importance. Thrombin inhibition has a direct action but also acts indirectly via its influence on thrombin mediated feedback loops. It is argued that rather than anti-factor Xa activity or prolongation of some type of coagulation time, the time-concentration integral of thrombin (thrombin potential) in clotting plasma should be used as a yardstick for the efficiency of a thrombin inhibiting drug. PMID- 1290383 TI - [Lyme disease]. AB - After a short historical review of the Lyme disease, the author describes the responsible bacteria, a Spirochete called Borrelia. Epidemiology, physiopathology and clinical manifestations are studied, as well as the different phases of the disease (primary secondary and tertiary) and the various possible symptoms (dermatological, cardiovascular, rheumatical, neurological syndrome). The biological part includes isolation of the Bacteria and detection of antibodies (IFI, ELISA, passive hemagglutination and Western Blot). Prophylaxy and treatments are also presented. PMID- 1290384 TI - [Aromatic and polyphenolic composition of infused peppermint, Mentha x piperita L]. AB - The qualitative and quantitative composition of the main aromatic and polyphenolic constituents of Mitcham type peppermint (Mentha x piperita L.) tisane, were examined and compared with those of leaves before and after infusion. The original peppermint leaves contained 2.4% essential oil of which menthol was 0.99%, total polyphenolic compounds 19% and total flavonoid compounds 12% comprising eriocitrin 7%, luteolin-7-rutinoside 1.5%, hesperidoside 0.6% and total hydroxycinnamic compounds 7% (rosmarinic acid 1.4%). The tisane contained 21% of the original essential oil corresponding to 25 mg/l, with increased alcohol and ketone contents and lower contents of hydrophobic terpenecarbons, oxides and esters. It contained also a high proportion of the polyphenolic compounds (about 750 mg/l) corresponding to an extraction yield of 75%. In consequence the monograph "Peppermint leaf" of the Pharmacopoeia should be amended. PMID- 1290385 TI - [Campaign against allergenic moulds in dwellings. Inhibitor properties of essential oil of Geranium 'Bourbon', citronellol, geraniol and citral]. AB - Many fungal airborne spora show allergenic effects. Indoor (dwelling, work rooms, hospital chambers) can be disinfected by elimination of living particles. We have undertaken experiments in more and more spacious bulks for evaluation of the antifungal effects of vapours of essential oils and some volatiles compounds. Results show that the Mucorales and Geotrichum resist strongly. On the contrary, the Cladosporium strains, some Aspergillus and Penicillium, Trichothecium roseum are the most sensitive, specially towards the citral vapours. Experiments in hospital can be undertaken. PMID- 1290386 TI - [HPLC used in the validation of simple methods for research of degradation products in essential drug tablets]. AB - HPLC have been used to validate simple methods to be employed in developing countries (DC) for the quality control of drugs. As the important lack of analytical material in DC, colorimetric methods have been used. These are subjected to visual appreciation of the color intensity. Two essential drugs have been selected: aspirin, hydrochlorothiazide. For each compound, standardization of concentration's degradation product by colorimetry and HPLC have been achieved in proximity of the restricted norms of pharmacopoeia. These results have been applied to tablets exposed to stressed conditions (t(0) = 60 and humidity = 75%). The results obtained by colorimetric method were similar to HPLC's ones. PMID- 1290387 TI - [Measurement of pacemaker effect: incidences on the choice of pacing mode? A prospective and statistical study of 396 patients]. AB - Single ventricular stimulation induces haemodynamic disturbances, the best known of which is the pacemaker syndrome. In order to assess the prevalence and severity of these abnormalities, invasive blood pressure monitoring was performed in 396 consecutive patients undergoing endocavitary electrophysiological investigations: a decrease in systolic blood pressure at a rate near to that of the spontaneous rhythm defines the pacemaker syndrome. It is maximal after 3 to 5 beats of equivalent intensity with or without retrograde conduction. The pacemaker syndrome is greater in hypertensive and coronary patients than in subjects with healthy hearts (-44.2 mmHg and -37.2 mmHg versus -33 mmHg, p < 0.001 and p < 0.04). It is less pronounced in cases of cardiac failure (-31.8 mmHg). The pacemaker syndrome increases in intensity with age (-44.3 mmHg after 80 years of age versus -23.1 mmHg in subjects under 50 years of age; p < 0.001). Two electrophysiological abnormalities are associated with an increased pacemaker syndrome even in apparently normal hearts: sustained induced supraventricular tachycardia (-34.2 mmHg versus -26 mmHg, p < 0.002), mixed carotid sinus syndromes (-38 mmHg) and pure vasodepressive syndromes (-48.5 mmHg, p < 0.001). The study of the pacemaker syndrome is useful for three reasons: the detection of another cardiac abnormality in cases of sustained induced supraventricular tachycardia, even in an apparently healthy heart; to assess the presence of a second haemodynamic abnormality independent of the vagal effect in cases of carotid sinus syndrome with vasodepression; finally, to identify the patients at high risk of a pacemaker syndrome. PMID- 1290389 TI - [Characteristics and prognosis of ventricular tachycardia induced by atrial fibrillation]. AB - The aim of this study was to evaluate the clinical significance of ventricular tachycardia (VT) induced by atrial pacing. A group of 145 patients with spontaneous and induced VT was studied. Twenty-four VTs were induced by atrial stimulation (Group I) and 121 by ventricular stimulation (Group II). The underlying cardiac disease was comparable in the two groups (ejection fraction 32 +/- 14% versus 34 +/- 17%). Spontaneous bi-tachycardias, syncope and VT induced by exercise testing were more common in Group I. The prognosis was worse with 7 cardiac deaths in Group I versus 23 in Group II; recurrences of VT were commoner in group I. In this group, an electrophysiological (branch to branch or fascicular reentry) or clinical mechanism (ischaemia or poor haemodynamic status) could usually be demonstrated. Some cases of idiopathic VT were also observed in young patients. These results suggest that atrial stimulation should be performed routinely during electrophysiological studies of VT because the induction of VT by this method is not uncommon (16%). In addition, these cases of VT usually have a precise mechanism and a poor prognosis and, therefore, an appropriate treatment should be given. PMID- 1290388 TI - [Evaluation of non invasive methods for the diagnosis of atherosclerosis of the graft after orthotopic cardiac transplantation]. AB - The frequency and severity of atherosclerosis of the cardiac transplant make it an essential complication of cardiac transplantation. Coronary angiography is the usual diagnostic method but it has severe limitations. In order to evaluate other diagnostic methods coronary angiography and non-invasive techniques: echocardiography, exercise stress ECG, exercise radionuclide ejection fraction, stress Thallium scintigraphy, were performed practically simultaneously in 60 patients after cardiac transplantation. These non-invasive methods were said to be positive in the presence of, respectively, a segmental wall motion abnormality, ischaemic ST segment depression, absence of increased ejection fraction on exercise, reversible or irreversible myocardial hypofixation. Coronary angiography was considered as the reference procedure for distinction between "normal coronary circulation" (no angiographically detectable lesion) and "graft atherosclerosis" (at least one coronary stenosis irrespective of the severity and extension). None of the non-invasive methods had an adequate sensibility when compared with coronary angiography (echocardiography 0.27, exercise stress ECG 0.28, exercise radionuclide ejection fraction 0.64, myocardial scintigraphy 0.62) or negative predictive value (echocardiography 0.56, exercise stress ECG 0.58, exercise radionuclide ejection fraction 0.68, myocardial scintigraphy 0.66). This inadequacy of the non-invasive technique may be explained by the fact that they are more adapted to the diagnosis of myocardial ischaemia than that of coronary studies. In addition, the extent of the coronary lesions may have masked discordance between 2 segments by the global hypovascularisation. The results of this study indicate that the non-invasive methods studied cannot be recommended for diagnosis of atherosclerosis of cardiac transplants. PMID- 1290390 TI - [Value of early systematic postoperative transesophageal echocardiography in mitral valve replacements. A prospective study of 50 patients]. AB - The aim of this study was to assess the value of routine transoesophageal echocardiography in the early postoperative period after mitral valve replacement. The authors report their experience in 50 consecutive operated patients (43 mechanical and 7 bioprostheses) investigated routinely by this method in the postoperative period in the surgical unit. Abnormal findings were observed in 36% of cases (18 patients): trans-prosthetic leaks (8 cases) and thrombosis (10 cases) in 2 bioprostheses and 8 mechanical prostheses; in 3 cases this led to haemodynamic dysfunction but in 7 cases the thrombus had no influence on the trans-prosthetic pressure gradient. No predisposing factor could be identified (spontaneous contrast, left atrial volume, left ventricular function, poor anticoagulation, blood clotting abnormalities). No abnormality of the mobile components of the prosthesis was observed at radioscopy. The outcome with heparin therapy was favourable with disappearance of the thrombi in 6 cases; the thrombi did not regress in 4 patients on heparin: 2 patients underwent thrombolytic therapy with a complete cure in 1 case and a severe embolic complication in the other; in 2 cases, the thrombus was so big that the patients were reoperated. Systematic early postoperative transoesophageal echocardiography before discharge from the surgical unit would seem to be necessary after early mitral valve replacement: it allows diagnosis of asymptomatic thrombosis which has an important emboligenic potential. The management of these thromboses remains controversial, but the poor natural outcome in cases of large thromboses should lead to referral for early reoperation. PMID- 1290391 TI - [Relationship between right ventricular ejection fraction and pulmonary pressure in man]. AB - This clinical study analysed the changes in right ventricular ejection fraction induced by changes in right ventricular afterload using a new thermodilution catheter linked to a rapid response computer which allowed instantaneous measurements of the right ventricular ejection fraction. The first group comprised 16 patients referred for coronary angioplasty with single vessel disease (isolated proximal stenosis of one of the two main branches of the left coronary artery) and a normal left ventricular ejection fraction (> or = 55%) and mean pulmonary artery pressure of < 25 mmHg: right ventricular ejection fraction and mean pulmonary artery pressure were measured under basal conditions and after 60 seconds' coronary occlusion with the balloon catheter in order to assess the effects of the reactional increase in afterload on the right ventricular ejection fraction. The second group comprised 11 patients with dilated primary cardiomyopathy with decreased left ventricular ejection fraction (< 50%) and mean pulmonary artery pressure > or = 25 mmHg: the right ventricular ejection fraction and mean pulmonary artery pressure were measured under basal conditions and after intravenous trinitrin (performed to evaluate the pulmonary reaction to vasodilators) in order to analyse the effects of the reduction of afterload on right ventricular ejection fraction. Negative linear correlations were observed between the right ventricular ejection fraction and mean pulmonary artery pressure under basal conditions (r = -0.72; p < 0.005) and between the right ventricular ejection fraction and mean pulmonary artery pressure after changing the conditions of afterload (r = -0.82; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290393 TI - [Measurement of right ventricular dP/dt. A simultaneous/comparative hemodynamic and Doppler echocardiographic study]. AB - Right ventricular systolic function is difficult to assess by Doppler echocardiography. We studied 14 patients with tricuspid regurgitation on Doppler echocardiographic examination with the object of determining an index of right ventricular contractility based on the continuous Doppler signal of the regurgitant jet. The rate of increase in right ventricular pressure was calculated between 2 points, V1 and V2, situated on the ascending limb of the velocity profile of the tricuspid regurgitation and compared with the dP/dt max measured simultaneously at right heart catheterisation. The different values of V1 and V2 were: 0 and 1 m/s, 0 and 2 m/s, 0.5 and 1.5 m/s, 1 and 2 m/s and 0.5 and 2 m/s. An excellent correlation was observed between the catheter dP/dt max and the rate of increase in pressure measured by Doppler between 0 and 2 m/s (r = 0.93; p = 0.0001) and between 0.5 and 2 m/s (r = 0.93; p = 0.0001). The correlation was not as close between 0 and 1 m/s (r = 0.69; p = 0.048) and there was no correlation with the measurements between 0.5 and 1.5 m/s and between 1 and 2 m/s. Doppler echocardiography could therefore be used for non-invasive assessment of right ventricular systolic function in clinical practice. PMID- 1290392 TI - [Comparative effects of anti-arrhythmia agents on ventricular refractory period and prevention of ventricular tachycardia induced by stimulation]. AB - The efficacy of antiarrhythmic drugs is attributed to their actions on the refractory periods or conduction velocity in the reentry circuit. The aim of this study was to determine the relationship between these factors and the prevention of electrically inducible ventricular tachycardia (VT). Twenty-seven patients with sustained monomorphic postinfarction VT underwent programmed stimulation under basal conditions and after administration of oral Class I antiarrhythmic drugs. The protocol of stimulation consisted of delivering one to three extrastimuli to the right ventricular apex on two basic cycle lengths. Sustained VT was induced in all patients. After the same protocol under antiarrhythmic therapy (1 to 5 tests, average 2.9 +/- 1) sustained VT could not be induced in 12 patients (44%). The effective right ventricular refractory period was significantly increased in patients without inducible VT under treatment (247 +/- 18 versus 302 +/- 26 ms). The increase in the right ventricular effective refractory period in patients with persistence of inducible VT was much less (from 270 +/- 28 to 287 +/- 30 ms). In all patients in whom several antiarrhythmic drugs were tested the right ventricular effective refractory period was higher when the treatment was judged to be effective (299 +/- 27 ms) than ineffective (272 +/- 27, p < 0.02). The prevention of inducible VT by class I antiarrhythmic agents seems therefore to be related to their effect on the ventricular refractory period. PMID- 1290394 TI - [Effects of electrocautery on the threshold values of permanent pacing. An experimental study]. AB - One of the hazards of high frequency electrical interference (electrocautery) with cardiac pacing is thought to be related to an increase in the threshold values leading to loss of pacing. This hypothesis was examined in an experimental study performed on 5 dogs. A pacing catheter was introduced via the right jugular vein and positioned at the apex of the right ventricle and connected successively to several stimulators implanted in a latero-cervical subcutaneous pocket. A Bovie 400 CT generator was used to deliver a high frequency 1.75 MHz current between a probe applied near to the pacemaker pocket and an electrode placed under the right leg. One or two 5 second bursts were applied for each make of pacemaker, making a total of 3 to 6 applications per animal. A detecting circuit enabled the measurement of the currents in the catheter during the application. The thresholds of pacing were measured before and after each manipulation for several pacing impulse durations. At the maximal output of the generator, the highest recorded current was 117 mA (modulated) and 141 mA (unmodulated). The thresholds of stimulation did not change significantly and the pacing catheter impedance was also stable. This study suggests that high frequency current does not modify the threshold of stimulation in cardiac pacemaker patients. The loss of pacing sometimes observed after the use of electrocautery is probably related to pacemaker dysfunction. PMID- 1290395 TI - [Financial management of clinical cardiovascular research in France from 1985 to 1990]. AB - From 1985 to 1990, 31.5 MF were distributed for clinical cardiovascular research in France by: the Institut national de la sante et de la recherche medicale (INSERM): 7.7 MF (25%); the Societe Francaise de cardiologie (SFC): 4.6 MF (15%) comprising 3.4 MF from its own resources (74%) and 1.2 MF from the pharmaceutical industry (26%); the Federation Francaise de cardiologie (FFC): 9.4 MF (30%) comprising 6.4 MF (68%) from its own resources and 3 MF from the pharmaceutical industry (32%); the pharmaceutical industry directly: the Searle Foundation; 4.8 MF (15%); and the Bank Credit Lyonnais: 5 MF (15%). The pharmaceutical industry therefore donated directly or indirectly via the SFC or the FFC, 9 MF or one third of the total sum attributed for cardiovascular research. Globally, over the period 1985-1990, the sums invested in cardiovascular research have doubled. The largest increase was related to the efforts of cardiologists themselves and their professional institutes: the SFC (by a factor of 3.7) and the FFC (by a factor of 2.5). On the other hand, independent donations and grants received from the pharmaceutical industry, the bank and Inserm have remained at the same level. PMID- 1290396 TI - [Parkinson syndrome, a possible adverse effect of calcium inhibitors]. AB - The effects of calcium inhibitors are not limited to the muscles and may affect other systems and cause varied side effects. Two cases of Parkinsonian syndrome occurring after starting therapy with calcium inhibitors (verapamil in one case and diltiazem in the other) are reported. Complete regression of the symptoms after withdrawing the drugs was strongly in favour of a causal relationship. The condition could be due to inhibition of the calcium channels in the central nervous system disturbing neurotransmission. This seems to be a rare side effect as there have only been three other reported cases of secondary extrapyramidal syndromes in the literature. However, a Parkinsonian syndrome is very invalidating and clinicians using this family of drugs should be aware of this possible complication. PMID- 1290398 TI - [Tamponade without cardiac rupture after repetitive thrombolysis in acute myocardial infarction]. AB - The authors report the case of tamponade without cardiac rupture 48 hours after a second course of intravenous thrombolytic therapy undertaken for unstable angina in laterobasal infarction in a 72 year old woman. The outcome after ultrasonic guided pericardiocentesis and surgical drainage (700 cc) was favourable. This is a rare complication of thrombolytic therapy (10 cases) and usually observed after anterior myocardial infarction. PMID- 1290397 TI - [Early constrictive pericarditis after coronary revascularization. Apropos of a case]. AB - The authors report a case of severe constrictive pericarditis occurring 6 weeks after coronary bypass surgery and in the absence of any other predisposing factor. The diagnosis was confirmed by CT scan and cardiac catheterisation which showed signs of a diastole. The patient died despite early surgical reoperation because of the severity of the pericardial fibrosis. PMID- 1290399 TI - [Focal junctional tachycardia in adults. Anatomo-electrophysiological aspects apropos of a case]. AB - The authors report the case of a 65 year old patient with focal junctional tachycardia complicating infectious myocarditis which had a fatal outcome. The ECG recordings showed episodes of tachycardia alternating with junctional rhythm at 90/min. There were signs of retrograde conduction. The anatomopathological findings were typical of acquired myocarditic lesions in the lower part of the atrioventricular node with congenital abnormalities, in particular a bifid node and His bundle with an accessory paraseptal atrioventricular bundle. This is the first description, to the best of the authors's knowledge, of junctional tachycardia associated with a latent pre-excitation. PMID- 1290400 TI - [Right atrioventricular metastasis of myxoid liposarcoma. Prolonged course after repeated surgery and chemotherapy]. AB - The authors report a case of cardiac metastasis of a myxoid liposarcoma of the thigh in a 54 year old woman. The treatment associated repeated surgical ablation and chemotherapy. The drugs used induced some cardiotoxicity which limited their prescription but nevertheless, the patient survived 5 years. Previous reported cases do not describe survival lasting more than 2 years and associated chemotherapy would therefore seem to be a valuable adjuvant, increasing the life expectancy of such patients. PMID- 1290401 TI - [Coronary accelerated arteriosclerosis and vasospasm in the transplanted heart]. AB - Accelerated atherosclerosis of cardiac grafts is one of the factors limiting long term survival after cardiac transplantation. The authors report the case of a patient who had a cardiac arrest associated with severe atherosclerosis 18 months after transplantation. The severity of the coronary lesions was underestimated by coronary angiography. An ergometrine test induced coronary spasm, a phenomenon which has only rarely been observed in transplanted hearts. The patient died one month later despite calcium inhibitor therapy. Autopsy revealed very severe triple vessel disease. This case illustrates the possible rapid evolution of coronary artery disease in cardiac transplant recipients, the difficulty in evaluating the severity of the lesions by coronary angiography and the additional possibility of observing coronary spasm in these cases. PMID- 1290402 TI - Single-dose toxicokinetics of aluminum in the rat. AB - The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12,000 micrograms Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12,000 micrograms Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12,000 micrograms/kg. At IV doses between 10 and 1000 micrograms/kg the terminal half-life of elimination from whole blood (t1/2 beta) increased from 29.9 +/- 7.8 to 209.3 +/- 32.6 min, and the total body clearance (CL) decreased from 2.45 +/- 0.64 to 0.28 +/- 0.03 ml min-1 kg-1. Following an IV bolus of 10 and 100 micrograms/kg the administered Al was recovered completely from urine (94.4% +/- 9.9% and 98.5% +/- 3.2%). Twenty-nine days after the IV dose of 1000 micrograms/kg daily renal excretion decreased to baseline values while only 55.1% +/- 8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 micrograms/kg Al accumulated in liver (28.1 +/- 7.7 versus 1.7 +/- 0.5 micrograms/g of control rats) and spleen (72.5 +/- 21.1 versus < 0.4 microgram/g). After the single 1000 micrograms/kg IG dose no absorption of Al was detectable. The IG dose of 12,000 micrograms/kg resulted in a maximum blood Al level of 47.9 +/- 12.4 micrograms/l after 50 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290403 TI - Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation. AB - The effects of aluminum exposure on bone formation employing the demineralized bone matrix (DBM) induced bone development model were studied using 4-week-old Sprague-Dawley rats injected with a saline (control) or an aluminum chloride (experimental) solution. After 2 weeks of aluminum treatment, 20-mg portions of rat DBM were implanted subcutaneously on each side in the thoracic region of the control and experimental rats. Animals were killed 7, 12, or 21 days after implantation of the DBM and the developing plaques removed. No morphological, histochemical, or biochemical differences were apparent between plaques from day 7 control and experimental rats. Plaques from day 12 control and experimental rats exhibited cartilage formation and alkaline phosphatase activity localized in osteochondrogenic cells, chondrocytes, osteoblasts, and extracellular matrix. Unlike the plaques from control rats that contained many osteoblastic mineralizing fronts, the plaques from the 12-day experimental group had a preponderance of cartilaginous tissue, no evidence of mineralization, increased levels of alkaline phosphatase activity, and a reduced calcium content. Plaques developing for 21 days in control animals demonstrated extensive new bone formation and bone marrow development, while those in the experimental rats demonstrated unmineralized osteoid-like matrix with poorly developed bone marrow. Alkaline phosphatase activity of the plaques continued to remain high on day 21 for the control and experimental groups. Calcium levels were significantly reduced in the experimental group. These biochemical changes correlated with histochemical reductions in bone calcification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290404 TI - N-benzyl-N-lactyl dithiocarbamate treatment of mice after chronic cadmium administration. AB - Administration of N-benzyl-N-lactyl dithiocarbamate (BLDTC) to mice after chronic cadmium (Cd) administration evoked a prompt, dose-dependent reduction of the whole body burden; 75% of the retained Cd was mobilized and excreted after 20 i.p. injections of BLDTC at 1.0 mmol/kg/injection. This same dose regimen produced 71% and 98% reductions of the renal and hepatic Cd concentrations, respectively. There was no reduction by BLDTC of the endogenous level of any of seven other metals measured: iron, magnesium, selenium, copper, calcium, zinc, and manganese. Renal proximal tubular damage in mice which received Cd followed by BLDTC was much less than that observed in kidneys from mice which received Cd alone. Chronic Cd administration led to substantial epithelial vacuolar damage to renal distal tubules, and this process was not apparently reversed or antagonized by BLDTC treatment to the extent observed in proximal tubules. PMID- 1290405 TI - Ongoing hepatocellular regeneration and resiliency toward galactosamine hepatotoxicity. AB - In previous studies, we reported that the age-dependent hepatotoxicity of galactosamine (GalN) was evident in hepatocytes maintained in primary cultures. Cellular proliferation and tissue repair are not manifested in response to injury in this in vitro system. Neonatal (5-day) rats have ongoing hepatocellular proliferation in contrast to adult (5-month) rats, and should be therefore resilient to GalN toxicity. Liver injury was assessed by serum transaminases (ALT, AST), 3H-thymidine (3H-T) incorporation into nuclear DNA, and content of hepatocellular nuclear DNA. While the dose of 400 mg/kg did not cause any significant liver injury in the neonates, it did produce significant liver injury in adult rats. At a dose of 800 mg/kg, GalN produced significant injury in the neonates. Because 400 mg/kg causes clearly demonstrable liver injury in the adult and no injury in the neonates, this dose was used for further studies. In addition to the above measures of injury, uracil nucleotides (UTP, UDP, and UMP), glycogen, histopathology, and autoradiographic examination of liver sections were used to assess the liver injury in neonatal and adult rats. In a time-course study, all of the above were measured at 0, 12, 24, 36, 48 and 72 h after GalN administration. Serum enzyme elevations as well as the appearance of necrotic and swollen hepatocytes were maximal at 24 h in the adults rats. In contrast to these observations in the adult rats, none of these measurements indicated significant liver injury in the neonates. 3H-T incorporation into nuclear DNA was much higher in the neonatal liver in comparison to the adults reflecting the difference in regeneration. Hepatocellular nuclear DNA was also higher in the neonate and was significantly decreased due to GalN treatment. In the adult rats, the quiescent normal level of 3H-T incorporation and nuclear DNA content were further decreased at 12 h, increased at 48 h and returned to normal low, quiescent levels at 72 h. In the neonates mitotic activity of hepatocytes was higher than in the adult rats. In the adult rats, mitotic activity was increased at 48 h after GalN administration and returned to normal at 72 h. In the neonates GalN did not alter the mitotic activity significantly. These findings demonstrate that in the presence of hepatocellular regeneration, galactosamine toxicity is minimal while in the absence of it, clear toxicity is manifested. In conclusion, while perturbation in uracil nucleotides and related biochemical events may explain the infliction of liver injury by GalN in an age-dependent fashion, the extent of tissue repair impacts decisively on the final outcome of injury. PMID- 1290407 TI - Acute and subacute inhalation toxicity of silane 1000 ppm in mice. AB - Male ICR mice were exposed to silane 1000 ppm, a concentration 200 or 2000 times higher than the recommended occupational exposure limits by many countries and academic associations, for 1, 2, 4, and 8 h (phase I study) and for 6 h/day, 5 days/week, over 2 and 4 weeks (phase II study). Hematological and biochemical studies were performed, and the animals were examined for histopathological lesions of the cornea, nasal cavity, respiratory tract, lung, liver, kidney, spleen, pancreas, thymus, thyroid, bone marrow, salivary glands, esophagus, and testis. All mice in both studies survived until they were sacrificed. In the phase I study, no exposure-related changes were found as a result of the hematological, biochemical, or histopathological examinations. In the phase II study, hematological and biochemical examinations failed to reveal any exposure related changes, but mild irritation, manifested in the form of a small amount of exudate (eight out of ten animals), and inflammatory cells and/or necrotic cells on the nasal mucosa (six out of ten animals) was observed in the mice exposed to silane for 4 weeks. These findings suggest that silane toxicity and irritation are not severe. PMID- 1290406 TI - Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts. AB - The incubation of isolated hepatocytes in the presence of glucose plus glucose oxidase, a H2O2-generating system, resulted in extensive loss of cell viability, as expressed by the release of lactate dehydrogenase (LDH). Disturbance of metabolic functions such as glycogen and protein synthesis was also caused by H2O2, but in no case was malondialdehyde (MDA)-like products detected. The lytic effect of H2O2 was significantly enhanced by incubating hepatocytes in the presence of iron salts. Under these conditions, MDA-like products were detected, but lipid peroxidation and cell injury did not correlate. Iron chelators modulated the cytotoxicity of H2O2 in different (and opposite) ways: when iron was complexed with ADP, increased cell lysis was observed compared to uncomplexed iron plus H2O2. Iron-DTPA, on the contrary, decreased such a lytic effect. The preincubation of hepatocytes with desferrioxamine mesylate (Desferal; a strong iron chelator) abolished the cytolytic effects produced by the association of iron salts and H2O2, as well as the membrane oxidative injury due to H2O2 alone, thus suggesting the existence of an intracellular source of iron. This kind of mechanism (metal chelation rather than radical scavenging) is supported by the absence of any protective effect by some free radical scavengers against the oxidative injury induced by the association iron H2O2. Nevertheless, the glycogenolytic effects observed in the presence of H2O2 were not modified by Desferal. In our opinion, the cytotoxicity of the association H2O2 plus iron salts involves at least two different and independent mechanisms. PMID- 1290408 TI - [Elevated production of GM-CSF by peripheral blood mononuclear cells stimulated with mite antigens in children with bronchial asthma]. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine which can stimulate the proliferation and functions of eosinophils and neutrophils. We have studied whether peripheral blood mononuclear cells (PBMC), obtained from children with stable asthma, can produce GM-CSF through stimulation with crude Dermatophagoides farinae (Df) antigen in vitro. The patients had strongly positive RAST results for house dust mite Df. Levels of GM-CSF in PBMC culture supernatant were assayed by an enzyme immunoassay. When stimulated with Df antigen, patient's PBMC released significantly increased levels of GM-CSF compared with unstimulated ones. PBMC of non-allergic controls, however, did not. The addition of polymyxin B, an inactivator of endotoxin, did not suppress the Df antigen-induced production of GM-CSF. Levels of GM-CSF produced by PBMC stimulated with Df antigens were significantly higher in the patients than in the controls. These results indicate that PBMC of children with Df-allergic asthma, unlike those of non-allergic children, can produce elevated levels of GM-CSF by stimulation with Df antigens. PMID- 1290409 TI - [Increased granulocyte/macrophage colony stimulating factor production by mononuclear cells from patients with bronchial asthma]. AB - The in vitro production of granulocyte/macrophage colony stimulating factor (GM CSF) by mononuclear cells from the peripheral blood of patients with bronchial asthma (BA) was examined by enzyme-linked immunosorbent assay (ELISA). In 3 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF without stimulation. And in 5 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF in response to IL-2. Mononuclear cells from patients with other diseases (n = 13) and healthy volunteers (n = 6) did not release any detectable (> or = 7.5 pg/ml) GM-CSF. The culture media of mononuclear cells from BA patients showed activities for stimulating the proliferation and survival of eosinophils, and these activities were partially inhibited by anti-GM-CSF antibodies. GM-CSF production by mononuclear cells from BA patients treated with prednisolone was lower than that of mononuclear cells from untreated BA patients. And prednisolone showed a reduction in the GM-CSF production from mononuclear cells in response to IL-2. These results suggest that GM-CSF production by mononuclear cells may play a role in the pathogenesis of BA. PMID- 1290410 TI - [Serum eosinophil cationic protein (ECP) and major basic protein (MBP) levels in patients prepared for asthma attack]. AB - Serum ECP levels, serum MBP levels and blood eosinophil counts (Eo) were studied in patients prepared for asthma attack. Five severely asthmatic children were studied. Samples were taken just before their 33 times of home stay loading test. Serum ECP levels were significantly higher in the patients who suffered asthma attacks during their home-stay period than in those who did not. In addition, serum ECP levels were higher in the patients whose asthma attack started less than 12 hours after they returned home. However, there was no significant correlation either in serum MBP levels or peripheral eosinophil counts between these groups. These findings suggested that serum ECP levels increased in patients prepared for asthma attack. PMID- 1290411 TI - [Clinical manifestation and prognosis of respiratory syncytial virus infection in infants]. AB - To evaluate the clinical features of respiratory syncytial virus (RSV) infection and relation with bronchial asthma, 233 infants hospitalized for lower respiratory tract infection during winters from 1988 to 1990 were enrolled in this study. RSV antigen was detected from half of them by immunofluorescent antibody test. Children with RSV infection showed the characteristic findings as follows; wheeze (71.6%), elevated serum 2-5 AS activity, a marker for viral infection, low level of acute phase reactants. Patients whose family members with major allergy experienced more frequent episodes of wheeze. Since the initial RSV infection could cause wheeze among infants from atopic families and recurrent wheezy infants could be recognized as in the pre-stage of infantile asthma, we should follow these infants with RSV infection closely. PMID- 1290412 TI - [A new steroid therapy for difficult asthmatics--an induction and maintenance, two-step therapy]. AB - Beclomethasone dipropionate (BDP) administered by inhaler is a very useful drug for the treatment of bronchial asthma. In this therapy, it is very important to use steroids systematically to induce a complete remission of asthma attack (first step) and then begin to use BDP a dose of more than 800 micrograms to maintain remission (second step). We treated 27 difficult asthmatics with this therapy and found this new method very useful. The characteristics of asthmatics were as follows. 1) The age ranged from 37 to 82, and the mean age (+/- S.E.) was 58.9 (+/- 2.6) years old. 2) The onset age ranged from 27 to 74 with a mean age (+/- S.E.) of 46.9 (+/- 2.6) year old. 3) The number of non-atopy was 22 cases. 4) The follow-up duration ranged from 5 to 45 months with a mean (+/- S.E.) of 15 (+/- 2.0) months. The results were as follows. 1) The complete remission rate was 48%, partial remission 37% and unchanged 15%. 2) There was a significant increase only in %VC. 3) The peripheral eosinophil count was decreased significantly. 4) The log value of PC20 concentration by acetylcholine increased significantly by a factor of 2.94 to 3.28. 5) After this therapy, the mean serum cortisol level at 9:00 a.m. was 10.1 (+/- 3.8, S.E.) micrograms/ml. There were only 2 cases whose cortisol level were under the normal. 6) There were many oral side effects, namely stomatitis with 5 cases and hoarseness with 8. PMID- 1290413 TI - [Clinical significance of IgG4 antibody determination in children against egg white, milk, soybean and Dermatophagoides farinae]. AB - The measurement of IgE and IgG4 antibodies against egg white, milk, soybean and Dermatophagoides farinae was performed by FAST (fluorescence allergosorbent test) using 21 serum samples obtained from non-allergic children and 160 serum samples from atopic children with bronchial asthma and/or atopic dermatitis. Their antibody levels were evaluated for any association with disease severity and for clinical significance in establishing diagnosis. It was found that children with bronchial asthma showed lower levels of IgE antibodies against egg white, milk and soybean and higher levels of IgE antibodies against Dermatophagoides farinae compared with those of children with atopic dermatitis, while both groups showed higher levels of egg white and milk-specific IgG4 antibodies compared with non allergic children. These IgE and IgG4 antibody levels revealed a tendency to correlate with disease severity in patients with atopic dermatitis, while this was not observed in patients with bronchial asthma. The contribution percentages of IgG4 antibody determination, together with IgE antibody determination, in retrieving causal allergens were 71% for egg white, 70% for milk and 48% for soybean allergy, implying their diagnostic value in establishing clinical diagnosis. PMID- 1290414 TI - [Protein phosphorylations in granulocyte/macrophage colony-stimulating factor stimulated human peripheral blood eosinophils]. AB - Peripheral blood eosinophils from normal healthy subjects were isolated on a Percoll gradient and were incubated with [32P] orthophosphoric acid. 32P-labeled eosinophils were washed and stimulated with GM-CSF under different conditions. After reaction was stopped, SDS/PAG electrophoresis was performed along with autoradiographs to determine the incorporation of 32P into proteins. GM-CSF stimulated eosinophils produced an increase of 32P incorporation into the bands in the 31 kDa and 35 kDa areas after 30 sec and 1 min of stimulation. The increase of 32P incorporation was dependent on Mg2+ concentration and temperature, suggesting that proteins in the eosinophils with apparent molecular weights of 31 kDa and 35 kDa can be phosphorylated with the stimulation of GM CSF. PMID- 1290416 TI - [Studies on IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen in asthmatics]. AB - T-cell-derived lymphokine, IFN-gamma, has potent effects on B-cell differentiation and leukotriene C4 production in leukocytes, and inhibits the effect of IL-4 on IgE production. To investigate the role of IFN-gamma in the pathogenesis of bronchial asthma, we examined IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen and serum Candida specific IgG1 antibody from 20 asthmatics. The results were as follows: 1) IFN-gamma production in non-atopic severe asthmatics was significantly higher than in healthy subjects, atopic mild and moderate asthmatics, and atopic severe asthmatics (p < 0.05). 2) There was a significant correlation between IFN-gamma production induced by Candida antigen and serum Candida specific IgG1 antibody (r = 0.72, p < 0.01). These results suggest that IFN-gamma may play an important role in the pathogenesis of non-atopic severe bronchial asthma. PMID- 1290415 TI - [The signal transduction of serotonin secretion involves protein tyrosine phosphorylation in rat basophilic leukemia cells]. AB - We investigated the signal transduction of serotonin secretion by stimulation with DNP-Ascaris antigen or ionomycin in rat basophilic leukemia cells (RBL-2H3). The modes of action of antigen and ionomycin for serotonin secretion were shown to be similar. The treatment of cells with antigen resulted in increased tyrosine phosphorylation of 105 and 72 KDa proteins, in particular, the tyrosine phosphorylation of 72 KDa protein seemed to correlate with serotonin secretion. Furthermore, we observed that antigen stimulation caused a marked increase in inositol polyphosphates production, which derived from the tyrosine phosphorylation of phospholipase C-gamma in RBL-2H3 cells. On the other hand, treatment with ionomycin also resulted in an increase in tyrosine phosphorylation of 72 KDa protein, but did not induce inositol polyphosphates production. These results suggested that the activation of tyrosine kinase may be related to serotonin secretion, and that intracellular Ca2+ increase may also play an important role in this activation. PMID- 1290417 TI - [Allergy among Japanese patients with chronic fatigue syndrome]. AB - Allergy is a common feature of patients with chronic fatigue syndrome (CFS). Because of this strong association, we attempted to explore the prevalence of allergies among Japanese patients with CFS. Of the present 18 patients, 78% had allergies during their premorbid and/or postmorbid conditions. Their allergies were mainly cutaneous reactions including drug allergies and 43% of the patients had 2 or more allergic reactions. In the case of a premorbid condition, allergies improved spontaneously after onset of CFS. Clinical manifestations of CFS, however, became worse during the period of an association with allergies. Immunologic tests, including peripheral blood lymphocyte-subsets, blastogenesis, natural killer-cell functions and cytokine-assays, were not any correlation between both patients with and without allergies. PMID- 1290418 TI - The right to procreate: intellectual disability and the law. AB - The common law recognizes the right of every woman to bear a child and will not contravene that right unless there are compelling reasons for doing so. The issue of the right of intellectually disabled girls, below the age of 18 years, to ultimately bear a child has now been removed to the courts. Following a recent High Court decision, surgery resulting in the sterilisation of intellectually disabled minors cannot be performed without the sanction of the Family Court. Intellectually disabled women differ in that they are legally adults once they reach the age of majority with presumed full adult rights to consent to medical treatment. Other legal mechanisms are require when they lack this capacity. This article discusses the High Court case and others that have been heard in Australia recently. PMID- 1290419 TI - What effect will the Nurses Act 1991 have on maternity care? AB - The NSW Nurses' Act 1991 has far-reaching implications for midwifery and for childbearing families. There are several issues that cause concern. The primary issue is the potential employment of non-midwives in maternity care. This would be dangerous to the women being cared for because of the specialised knowledge required to practice midwifery. In some ways the act undermines the independence of midwifery from nursing and the value of midwifery care. Implementation of the act may also cause some role conflict in maternity units. PMID- 1290420 TI - Report and recommendations from the Joint Birth Consultative Committee. PMID- 1290421 TI - The Royal Women's Hospital Family Birth Centre: the first 10 years reviewed. AB - In reviewing the first 10 years experience of the Royal Women's Hospital Family Birth Centre (FBC), we examined the outcomes of pregnancy and labour in a group of women who requested alternative birthing care and who were identified antenatally as being a 'low-risk' population. This study is a retrospective analysis of 5,365 women booked with the birth centre between 1980 and 1989. Over 16% of women developed antenatal complications precluding further care there, while a further 16% developed complications in labour requiring transfer out to conventional labour wards. Thus 67% of those originally booked delivered in the FBC. The instrumental delivery rate was 11%, and the Caesarean section rate was 4%. Of the women who delivered in the FBC, 3.1% had a postpartum haemorrhage and 1.8% required manual removal of placenta. Approximately 4% of babies born in the FBC required some resuscitation, and 0.8% needed admission to the neonatal nursery. Two perinatal deaths occurred in women admitted in labour to the FBC with a live baby, whilst 2 other women presented in labour with a fetal death in utero (perinatal mortality 0.89 per 1,000). PMID- 1290422 TI - Organization and early results of a shared antenatal care programme. AB - The organization and function of a public hospital based shared antenatal care programme is described. The programme has proved to be popular with pregnant women and local practitioners and currently 24% of public antenatal patients attending the hospital are cared for in this way. The study presents the results of management of 1,000 consecutive low risk patients whose antenatal care was shared between hospital doctors at the Royal Women's Hospital, Melbourne and local practitioners. Two hundred and twenty patients did not complete the programme because of social factors, medical diseases or pregnancy complications. The 780 patients who did complete the programme had a lower Caesarean section rate than the overall hospital population (8.3% compared with 18.5%) and a lower perinatal mortality rate (6.4 compared with 20.5 per 1,000 births). It is essential that patients are carefully assessed at their hospital booking visit before embarking on such a programme. Equally, careful assessment by local practitioners is important as abnormalities such as essential hypertension may be overlooked at the initial hospital assessment or may arise between the hospital visits. PMID- 1290423 TI - Shared obstetric care: the general practitioner's perspective. AB - Shared obstetric care between hospital and general practitioner (GP) is being developed in several States in Australia as an alternative model of care for pregnant women in the public hospital system. The aim of this study was to determine the attitudes of participating GPs to the shared obstetric care programme at the Royal Women's Hospital, Melbourne. Fifty GPs were randomly selected, and face to face individual interviews were conducted using qualitative methods. GPs feel that the continuity of care they can provide during pregnancy and the postpartum is a very important and valuable aspect of their role as shared care providers. They are generally satisfied with the programme at the Royal Women's Hospital but some suggest that communication between the hospital and the GP should be improved. There was significant interest in being involved in deliveries in shared care programmes in the future and GPs question the appropriateness of the diploma of obstetrics as the only acceptable qualification for shared care. PMID- 1290424 TI - The demographic characteristics of early and late attenders for antenatal care. AB - In the Royal New Zealand Plunket Society's 1990-91 Cohort study, 581 of 4,286 women questioned (13.7%) had not initiated antenatal care until after the first trimester. These late attenders were more likely to be non-European or of high parity; 42.9% of Pacific Islander mothers and 28.9% of Maori mothers did not initiate antenatal care until after the first trimester. Late attenders were also more likely to be unmarried, of lower socioeconomic status, young or with lower educational attainment. The reason for delayed antenatal care needs to be investigated and mothers who are high parity and non-European need to be particularly targeted to encourage them to attend for antenatal care early. PMID- 1290425 TI - Perinatal mortality in a tertiary obstetric institution. AB - At the Royal Women's Hospital, Melbourne in the 3 years 1987-1989 analysis of the records of 13,347 public patients revealed an overall perinatal wastage of 20.8 per 1,000 births. This seemingly high figure resulted from the fact that 45% of losses occurred in nonbooked and emergency admissions. Many patients were referred with major complications of pregnancy, especially gross prematurity, lethal congenital malformations and intrauterine deaths. During the 3-year period 74% of perinatal losses occurred before 33 weeks' gestation and only 10% were after 37 weeks. By comparison at a Victorian State level, 47% of perinatal deaths occurred before 33 weeks and more than 35% after 37 weeks' gestation. The major causes of perinatal wastage in both groups were similar. At the Royal Women's Hospital in the 3-year period lethal congenital abnormalities accounted for 19.1% of fetal wastage, premature labour, premature rupture of the membranes and cervical incompetence 16.2%, multiple pregnancy 14.7%, antepartum haemorrhage 14.0% and hypertensive disorders 9.7%. During the 3-year period 7.7% of hospital stillbirths were intrapartum compared to 27% for the State of Victoria. The stillbirth rate in Victoria has declined over the past decade, but to a lesser extent than the neonatal death rate. Over the 3-year period 1987-1989 the ratio of stillbirths to neonatal deaths was 3 to 2, and in 1989 there were nearly twice as many stillbirths as neonatal deaths (424 versus 240). Furthermore, 55% of stillborn infants in Victoria had birth-weights of more than 1,500 g compared to the Royal Women's Hospital figure of 36%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290426 TI - The timing of delivery in diabetic pregnancy: a 10-year review. AB - The approach of term in the pregnancy of a diabetic woman is a time of anxiety for patient and physician alike. The impact of a conservative approach to the timing of delivery is outlined in this review of the clinical course and outcome of 276 pregnancies of diabetic women, delivered at the National Maternity Hospital, Dublin between 1981 and 1990. The mean gestation at delivery was 39 weeks, 229 patients (83%) delivered at or beyond 38 weeks and 112 patients (41%) delivered at or beyond 40 weeks. The overall induction of labour rate was 27% and the elective Caesarean section rate was 19%. Sixty seven percent of patients achieved a normal delivery, the forceps rate was 5%, and 28% of patients were delivered by Caesarean section. There were 16 perinatal deaths in the series, with 7 due to lethal malformations. There were 5 deaths of normally formed infants occurring at or beyond 38 weeks' gestation. All of these 5 deaths had been preceded by clinically apparent polyhydramnios or macrosomia and recognized poor control. This study stresses the value of strict diabetic control in the management of diabetic pregnancy and highlights the significance of polyhydramnios and macrosomia as indicators of risk approaching term in diabetic pregnancy. PMID- 1290427 TI - Excessive birth weight and maternal glucose tolerance--a 19-year review. AB - The incidence of birth-weight of 4,540 g (10 lb) or more rose from 0.87% in the years 1971 to 1977 to 1.16% in the 12 years from 1978 to 1989 with a concomitant increase in hyperglycaemia in our antenatal population. The relationship between excessive birth-weight and maternal glucose tolerance was investigated in the light of these observations. The results from glucose tolerance tests performed routinely during the pregnancies of 510 women who delivered infants with a birth weight of 4,540 g or more were compared with those from a control series of 5,003 women with consecutively tested pregnancies. Glucose tolerance in subsequent pregnancies was also compared with the control series, and in 1991 the study group women were investigated for emergence of permanent diabetes mellitus. Excessive birth-weight was associated with maternal hyperglycaemia (p < 0.05) but not with gestational diabetes; 79% of infants with birth-weight > or = 4,540 g were born to mothers who were not hyperglycaemic. There was no increase in glucose intolerance in subsequent pregnancies in the study group and only 2 of 49 women with follow-up testing had diabetes mellitus. Birth-weight > or = 4,540 g occurred in 1.1% of the total population and 1.1% of women with gestational diabetes, and was related to maternal hyperglycaemia in about 1 in 5 cases. The increased incidence of excessive birth-weight infants was not related to the increased incidence of gestational diabetes in our pregnant population. Birth weight > or = 4,540 g had a poor association with later development of diabetes. PMID- 1290428 TI - Gestational diabetes in twin pregnancy: prevalence and long-term implications. AB - During the period 1971-1991 at the Mercy Hospital for Women, gestational diabetes (GDM) was diagnosed in 3,447 of 61,914 tested singleton pregnancies (5.6%) and 59 of 798 tested twin pregnancies (7.4%, p = 0.025). A difference was apparent in the period 1971-1980, when the prevalences of GDM in singleton and twin pregnancies were 3.0% and 5.6% respectively (p = 0.012), but not in the period 1981-1991 when the corresponding prevalences were 7.4% and 8.4% (p = 0.36). Of the 59 patients in whom a diagnosis of GDM in a twin pregnancy was made, 27 attended the follow-up programme. These patients were matched to a control group of 27 patients who had GDM in a singleton pregnancy with similar characteristics for known risk factors for the development of permanent diabetes mellitus. On WHO criteria diabetes mellitus occurred in 5 (18.5%) of the subjects and 2 (7.4%) of the controls (p = 0.21). The difference in prevalence of GDM in twin and singleton pregnancies is less now that the overall prevalence of the disease has more than doubled (1971-1980 versus 1981-1991). Although the increased rate of permanent diabetes mellitus after twin pregnancy is not statistically significant, it would seem wise to make a special effort to enroll these women in the follow-up programme. PMID- 1290429 TI - Antiphospholipid antibodies in pregnancy. AB - We assessed the relationship between antiphospholipid antibodies and recurrent miscarriage, fetal deaths, and the pregnancy complications--placental abruption, fetal growth retardation and preeclampsia. The subjects were 81 women with a history of 3 or more miscarriages, 62 with a history of fetal death in the index pregnancy, 105 with a poor obstetric history or pregnancy complications and 13 with systemic lupus erythematosus. Antiphospholipid antibodies were found in 41% of women with a history of recurrent miscarriages, 29% with a history of recent intermediate fetal death or stillbirth, 19% with a poor obstetric history and 69% with systemic lupus erythematosus. There is a high incidence of antiphospholipid antibodies in complicated pregnancies. Patients presenting with the above pregnancy disorders should be tested for antiphospholipid antibodies because of the risk conferred on a fetus by their presence and to expand the treatment options. PMID- 1290430 TI - Neonatal herpes simplex: Royal Women's Hospital 10-year experience with management guidelines for herpes in pregnancy. AB - In the 10-year period 1982-1991 inclusive, 6 cases of neonatal herpes simplex were diagnosed at the Royal Women's Hospital, Melbourne (1 disseminated, 1 pneumonitis, 4 cutaneous [1 with central nervous system involvement]), resulting in an incidence of 1 in 11,000 livebirths for this population. Three cases were due to HSV 1 and 3 to HSV 2. In no case did the mother have a recent or past history of overt genital herpes infection. Two cases were acquired in utero, an uncommonly recognized form of infection. A favourable long-term outcome occurred in 2 of 4 cases in which diagnosis was prompt and antiviral therapy was instituted rapidly. Routine antenatal screening in the last trimester of pregnant women with a history of genital herpes before pregnancy is not advised, because the results have been shown to be unreliable in predicting viral shedding and hence the infants' risk of exposure to virus at delivery. A protocol for management of herpes in pregnancy is included. PMID- 1290431 TI - Antihypertensive drug effects on placental flow velocity waveforms in pregnant women with severe hypertension. AB - Doppler studies of the uterine and umbilical arteries were performed in 24 acutely hypertensive pregnant women. Women were divided into 2 groups: Group 1 (diastolic blood pressure (DBP) > 110 mm Hg) received placebo (n = 6) or 10 mg oral nifedipine (n = 9); Group 2 (DBP > or = 110 mm Hg) received 10 mg oral nifedipine (n = 5) or 10 mg intravenous hydralazine (n = 4). Treatment allocations were random within groups and the investigator and patient were blind to the treatments. Baseline flow velocity waveforms (FVW) and posttreatment FVW's at 30, 60 and 120 minutes were recorded. There was no significant difference between baseline and posttreatment FVW indices within or between groups. Placebo was as effective as nifedipine in lowering blood pressure over 2 hours of study. There were no significant adverse effects of treatment. PMID- 1290432 TI - Expected gain in body mass and onset of the menarche. AB - Fertility is dependent on sexual maturity, which is associated with a number of factors, including body mass. In this study the Body Mass Index (BMI) was used to estimate body fat in a large sample of 13-year-old New Zealand girls. Nearly half of the subjects (46%) had experienced the menarche. Expected gain in body mass was calculated from growth rates at earlier ages and used to examine whether deviation from the expected gain was associated with the onset of the menarche. In general, the results show an association between the menarche and gain in body mass. However, many girls who failed to achieve their expected gain had experienced the menarche (18%), indicating that the relationship between body weight and the menarche may not be causal or is mediated by other factors. PMID- 1290433 TI - Risk factors and a risk scoring system for the prediction of malignancy in ovarian cysts. AB - A retrospective study was carried out on 396 patients who presented with ovarian masses. Sixty five (16%) patients were found to have ovarian malignancy while the rest either had benign ovarian tumours (n = 159), endometriotic cysts (n = 130), physiological cysts (n = 20) or inflammatory masses (n = 7). The relative risk for ovarian malignancy among these patients increased significantly (p < 0.001) after the age of 40 years. The presence of ascites, abdominal distension, urinary complaints and loss of appetite and weight were significant individual risk factors for malignancy. Ultrasound image of a complex cyst is also associated with increased risk of malignancy in an ovarian mass. None of the individual risk factors was discriminatory between a benign and malignant cyst. However, these factors can be combined to form a 20-point risk scoring system. The risk of malignancy in an ovarian cyst increased with increasing scores. In this study, the median scores were 3 for benign cyst, 7 for borderline malignancy and 12 for malignant cysts. Using a total score of 7 as a cut off point, one can detect 75% of malignant cysts with a specificity of 84.1%, a positive predictive value of 47.5% and a negative predictive value of 94.6%. It is concluded that the majority of malignant ovarian cysts can be identified preoperatively to allow arrangement and planning of an optimal surgery. PMID- 1290434 TI - Danazol in the treatment of menorrhagia: the effect of a 1 month induction dose (200 mg) and 2 month's maintenance therapy (200 mg, 100 mg, 50 mg or placebo). AB - This paper highlights the difficulties of recruiting subjects to objective menstrual blood loss (MBL) studies. Such difficulties may explain the relative paucity of such studies in the literature. Eleven women with objectively assessed evidence of menorrhagia were treated for 1 month with an induction dose of 200 mg of danazol (Danocrine). Subsequently the women were randomly assigned to receive 50, 100 or 200 mg of danazol or placebo for 2 months of maintenance dosing. Follow-up with objective assessment of MBL was continued for 3 months after cessation of maintenance dosing. Danazol 200 mg as an induction dose significantly reduced MBL. The maintenance dose of 200 mg during the following 2 months produced a further decrease in MBL and in some cases amenorrhoea. The lower maintenance dosages of 50 mg and 100 mg were associated with a variable response. The study was unable to determine whether any beneficial effect of the maintenance dosages of danazol could be maintained following cessation of therapy since the study numbers had become too small. It appears, however, that there is unlikely to be any persisting benefit once therapy has ceased. PMID- 1290435 TI - Stress management and infertility. AB - The author through personal experience has gained knowledge in the area of infertility and stress management. Her professional background supports the experiences, emotions and management techniques encountered with sound theoretical knowledge. This article deals with some of the procedures confronting a couple who experience infertility problems. It aims to explain and qualify common emotional responses experienced by couples and offers stress management strategies to improve their coping ability. PMID- 1290436 TI - Uncertainties about endometrial ablation. PMID- 1290437 TI - Uterine perforation associated with endometrial ablation. AB - Three cases of uterine perforation associated with endometrial ablation are presented. Possible predisposing factors in 2 cases were previous Caesarean section and difficulty in cervical dilatation. Adequate training for gynaecologists in hysteroscopy is essential before undertaking any type of operative hysteroscopy. PMID- 1290438 TI - Laparoscopic adnexectomy--indications, technique and results. AB - Laparoscopic adnexectomy was performed successfully in 38 patients in whom the procedure was attempted. Failure may result from inexperience of the surgeon or when preliminary dissection near bowel suggests trauma is likely. The duration of the operation was between 15 and 105 minutes, blood loss was minimal and all but 2 patients were discharged within 24 hours of surgery. Pain was relieved in 33 of 35 patients in whom this was the dominant symptom. In 1 patient a small ovarian remnant implanted on the bladder was removed at subsequent laparoscopy. Preliminary experience of this procedure suggest it may be preferable to laparotomy because of the reduced risk of wound complications, pain, time in hospital and duration of convalescence. PMID- 1290439 TI - Laparoscopic salpingostomy with electrocautery in the management of tubal pregnancy. AB - From August, 1990 to May, 1991, all cases of tubal pregnancy presenting to King George V Hospital for Mothers and Infants were considered for laparoscopic salpingostomy. This procedure involved opening the affected Fallopian tube with diathermy, removal of ectopic tissue via the laparoscope, achieving haemostasis and leaving the tubal incision to heal by secondary intention. The procedure was undertaken in 35 patients and was successfully performed in 31 patients with an average operating time of 66.4 minutes (+/- 20.1 minutes). Average hospital stay was 2.1 days (+/- 1.3). This paper examines the technique and results of the initial learning curve for laparoscopic salpingostomy and finds that with knowledge of potential hazards and care in surgery, this operation can be safely carried out in a selected group of patients. PMID- 1290440 TI - Ultrasound diagnosis and laparoscopic excision of an interstitial ectopic pregnancy. AB - Interstitial tubal pregnancy occurs in about 5% of ectopic tubal pregnancies and is associated with an increased risk of severe haemorrhage (1). Diagnosis prior to rupture of the pregnancy into the peritoneal cavity is very important to avoid haemorrhage. Its presence has been considered to be a contraindication to laparoscopic surgery (2), although most ectopic pregnancies can be managed laparoscopically by an experienced endoscopist. We report the diagnosis of an interstitial pregnancy by ultrasound before rupture and treatment by laparoscopic excision of the pregnancy. PMID- 1290443 TI - Delayed fetal death following electrical injury in the first trimester. AB - A case of possible delayed fetal death following electrical shock in the first trimester is reported. Evidence from the literature of delayed effects of electrical injury later in pregnancy is presented, suggesting that delayed as well as immediate detrimental effects in the first trimester should not be discounted. Perhaps the spectrum of effects of electrical shock on the fetus could be investigated in animal experiments to elucidate the pathogenesis of such injury to the fetus. Electric fences are a possible hazard to pregnant women in rural areas. PMID- 1290442 TI - Placenta praevia percreta invading the urinary bladder. AB - A case of placenta praevia percreta involving the urinary bladder is presented. A classical Caesarean section was performed at 35 weeks' gestation but the placenta was left in situ and an elective hysterectomy was successfully performed 2 weeks postpartum. PMID- 1290441 TI - Outpatient hysteroscopy: a comparison of 2 methods of local analgesia. AB - A prospective, randomized study was undertaken to objectively compare pain tolerance of 2 methods of local analgesia for outpatient hysteroscopy. Patients in group 1 received a paracervical block using 20 ml of 1% lignocaine. Patients in group 2 received a uterosacral block using 2 ml of 2% lignocaine. There was no statistical difference between the 2 groups (p = < 0.65) in efficacy of pain relief. The method used for patients in group 2 reduces time and costs for outpatient hysteroscopy. PMID- 1290444 TI - External cephalic version--a cautionary tale. PMID- 1290445 TI - Topical application of honey in treatment of abdominal wound disruption. AB - The usefulness of honey application as an alternative method of managing abdominal wound disruption was assessed. Fifteen patients whose wound disrupted after Caesarean section were treated with honey application and wound approximation by micropore tape instead of the traditional method of wound dressing with subsequent resuturing. We achieved excellent results in all the cases with complete healing within 2 weeks. Honey application is inexpensive, effective and avoids the need to resuture which also requires general anaesthesia. PMID- 1290446 TI - Prescription drugs in the first trimester and congenital malformations. PMID- 1290447 TI - Free full thickness vaginal epithelium graft in correction of recurrent genital prolapse. PMID- 1290448 TI - Ruptured ectopic pregnancy in an amenorrhoeic women after transcervical resection of the endometrium. PMID- 1290449 TI - Recombinant-inbred strains: application to behavioral phenomena. PMID- 1290450 TI - Recombinant-inbred strains: general methodological considerations relevant to the study of complex characters. AB - If appropriately determined, recombinant-inbred (RI) strain means provide an excellent method for determining genetic correlations among complex characters. However, little systematic attention has been paid to important environmental influences on strain means such as random effects due to litter membership or systematic maternal influences, which are inevitably confounded with genetic effects. It is suggested that users of RI strains would do well to control for litter effects by sampling appropriately from many litters and assessing the potential role of maternal influences by appropriate fostering procedures. Concern for these and other environmental sources of variation has caused reliability of strain means to emerge as an important issue in studies with RIs which focus on complex characters. Examples of estimating the reliability of RI strain means are provided to draw attention to the value of this kind of information in both gene-mapping studies and genetic correlational analyses. In addition, particularly in the case of behavioral tests which are susceptible to considerable day-to-day variation, repeated testing of the same animals can serve to diminish the influence of extreme deviations which are due to random variations in the manner in which the test is conducted on any given day. The advantages of RIs for gene mapping are well established. However, via the power of genetic correlational analysis, the RI methodology is emerging as a major alternative method, e.g., as distinct from lesion studies, pharmacological interventions, etc., in the bio-behavioral sciences to explore relationships between different domains of inquiry. Via its cumulative and integrative power, it is likely to make a major contribution to investigations of relationships between complex characters at various levels of and this application which should be considered separately from its application to gene mapping. PMID- 1290451 TI - Chromosome mapping of Soa, a gene influencing gustatory sensitivity to sucrose octaacetate in mice. AB - Strain distribution patterns among recombinant inbred strains suggested that a locus influencing taste sensitivity to sucrose octaacetate was on chromosome 6. A location for Soa was established by linkage analysis of behavioral and electrophoretic data from outbred and congenic strains and from test-cross progeny. Haplotyping of 41 outbred CFW-Cr animals with a cDNA probe showed perfect cosegregation of Soa and Prp, a gene for salivary proline-rich proteins. Five of twelve B6.SW-Soaa strains were found to retain Ldr-1, lactate dehydrogenase regulator-1, on chromosome 6 as an allelic passenger from the SWR/J donor strain (source of the Soaa Taster allele). Centimorgan distance was estimated using the ABP/Le linkage-testing strain (non-Taster, Soab) and the SWR/J strain (Taster, Soaa) in a testcross breeding system. The data are consistent with a position for the Soa locus on mouse chromosome 6, 62 cM from the centromere. PMID- 1290452 TI - Inference in linkage analysis of multifactorial traits using recombinant inbred strains of mice. AB - Recombinant inbred strains have been shown to be important tools for segregation and linkage analysis of multifactorial traits. Tests of association have been used as robust methods of linkage detection, however, guidelines for forming inferences from significance levels have not been generally available. In this paper, lessons learned from a Bayesian statistical approach to linkage analysis of Mendelian traits have been applied to studies of multifactorial traits. Criteria for detection of linkage based on Bonferroni's correction for multiple testing are also discussed. PMID- 1290453 TI - Empirical estimates of Bonferroni corrections for use in chromosome mapping studies with the BXD recombinant inbred strains. AB - Most chromosome mapping efforts with the BXD recombinant inbred (RI) strains involve comparisons between a trait of interest and each of a large number of marker loci for evidence of linkage. Such multiple tests or comparisons greatly increase the Type I error rate compared to the single-test situation. Perhaps the most direct way to obtain multiple-test error rates is to employ a Bonferroni correction, where the single-test alpha is multiplied by the number of independent (nonredundant) comparisons (k) to yield a multiple-test alpha that protects against even one fortuitous association with any of the markers. Several empirical estimates of k are discussed for the published BXD marker set of 142 mapped loci and the newer unpublished marker set (October 1991) comprised of 352 marker loci. Reasonable estimates of k appear to be roughly 40 and 65 for these two marker sets, respectively. PMID- 1290454 TI - Recombinant congenic strains of mice from B10.D2 and DBA/2: their contribution to behavior genetic research and application to audiogenic seizures. AB - Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain ("donor" strain) on the genetic background of another strain ("background" strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength. PMID- 1290455 TI - Free radical generation in hydroperoxide-treated erythrocytes monitored continuously by luminol-amplified chemiluminescence. AB - Organic hydroperoxides induce oxidative damage to mammalian cells. We describe how luminol-amplified chemiluminescence can be used to monitor free radical generation (following treatment of erythrocytes in vitro with organic hydroperoxides) throughout the entire time-course of oxidative stress. Enrichment of erythrocyte alpha-tocopherol levels increased the induction time by 25% and led peak chemiluminescence fall of 30%. Furthermore, ascorbate loading reduced the signal four-fold during the induction period. The catalytic role of haemoglobin was shown by the abolition of chemiluminescence by azide and a low (but detectable) signal in haemoglobin-depleted erythrocyte ghosts. Luminol amplified chemiluminescence enables the kinetics of free radical generation to be monitored continuously. Furthermore, it may enable features of the mechanism of interaction between cellular antioxidants and antioxidant enzymes to be elucidated. PMID- 1290456 TI - Expression of salivary mucin bacterial aggregating activity: difference with caries. AB - The low and high molecular weight mucin forms were isolated from saliva of individuals with different caries status and assessed for their bacterial aggregating potential towards S. mutans and S. sanguis. The high molecular weight mucin from both groups exhibited similar protein and carbohydrate content, but the level of covalently bound fatty acids was lower in the caries-resistant group. The mucin from caries-resistant group showed only a weak inhibitory potential, while no inhibitory activity was observed with the mucin of caries susceptible group. The low molecular weight mucins from both groups, while displaying compositional similarities, showed a marked variation in the bacterial aggregating activity, and the titer of the mucin from caries-resistant group was at least 128-fold greater than that of caries-susceptible group. The results demonstrate that the bacterial aggregating epitope of salivary mucins is expressed to a greater extent in caries-resistant individuals, and that this epitope is apparently more accessible to bacteria in the low molecular weight mucin form. PMID- 1290457 TI - Alterations in the methylation of membrane phospholipids in the uterus and post implantation embryo following exposure to teratogenic doses of alcohol. AB - The intragastric administration of alcohol to pregnant mice at 3.0 g/kg body weight, but not at 0.5 or 1.5 g/kg body weight, adversely influenced embryonic growth and increased the rate of methyl group incorporation from S-adenosyl-L [methyl-3H]methionine into uterine endometrial plasma membrane phospholipids. These changes involved phosphatidylcholine, phosphatidyldimethylethanolamine, and phosphatidylmonomethylethanolamine when the alcohol was acutely administered, but only phosphatidylcholine when the drug was given in a semi-chronic regime. Similar alterations were not detected in post-implantation embryos exposed to alcohol either in vitro or in vivo. The results suggest that maternal exposure to alcohol during early post-implantation pregnancy can alter the pattern of phospholipid methylation in the uterus, but not in the embryo, which may facilitate biochemical changes that adversely influence the ability of the maternal system to support embryonic development. PMID- 1290458 TI - Comparison of supernatant-and ribosome-bound rat liver tRNA. AB - Transfer RNAs were separated into a ribosome bound fraction and a supernatant (cytoplasmic) fraction. The nucleoside composition, 2-dimensional PAGE pattern and in vivo labeling were compared. 12 minor nucleosides were identified by HPLC. In general, the minor nucleosides, especially N2-methyl-guanidine and ribothymidine, were higher in the ribosome-bound fraction. The PAGE patterns were similar but there were quantitative and qualitative differences among the smaller spots. In vivo labeling by 32P showed that new tRNA goes preferentially to the ribosome but mixing does occur. The results suggest the existence of two compartments of tRNA. PMID- 1290459 TI - The stimulatory and inhibitory effects of glycyrrhizin and a glycyrrhetinic acid derivative on phosphorylation of lipocortin I by A-kinase in vitro. AB - The effects of GL and oGA on the activity (phosphorylation of lipocortin I) by A kinase were investigated in vitro. It was found that (i) phosphorylation of the 35-36 kDa polypeptide by A-kinase was inhibited selectively when the partially purified kinase fraction from EAT cells was incubated with [gamma-32P]ATP in the presence of 60 microM oGA; (ii) the marked polypeptide was identified as a lipocortin I; and (iii) the activity of the kinase was stimulated about 4-fold by 5 microM oGA, but it was inhibited at doses above 25 microM. The drug-induced inhibition of phosphorylation of lipocortin I by A-kinase may be implicated in the anti-inflammatory effect of the drugs. PMID- 1290460 TI - Cytotoxicity of human beta-interferon produced in human glioma cells transfected with its gene by means of liposomes. AB - The cytotoxicity of human beta-interferon (HuIFN-beta) produced in human glioma cells was examined by use of our liposomes entrapping two plasmids, pSV2neo and pSVMTV-IFN-beta. After the cells had been transfected with these genes by means of the liposomes, neomycin-resistant cells were selected. When the selected cells were subjected to a single exposure to dexamethasone, all of the cells were found to produce HuIFN-beta and were eliminated by 8 days. Accordingly, the effect of HuIFN-beta produced in human glioma cells is considered to be cytocidal. PMID- 1290462 TI - Crosslinking of proteins in acetylcholine receptor-rich membranes from Torpedo californica: relation of 43-kD protein and Torpedo dystrophin to acetylcholine receptor. AB - We examined the spatial relation of 43-kD protein and Torpedo dystrophin, which are cytoplasmic peripheral membrane proteins in the nicotinic acetylcholine receptor (AChR)-rich membranes, to AChR. We used three kinds of the heterobifunctional crosslinking reagents to crosslink proteins in the AChR-rich membranes. Products crosslinked by SMPB (14.5 A span) including 43-kD protein and Torpedo dystrophin appeared at the tops of the stacking gels at the concentrations of 8.89 x 10(-5)M to 8.89 x 10(-3)M SMPB. High molecular weight materials (crosslinked products) increased with increasing concentrations of the crosslinker. On the other hand, band intensity of alpha, beta, and delta subunits of AChR remained unchanged up to a concentration of 2.67 x 10(-3)M SMPB, while the band of gamma subunit diminished at the same concentrations as did that of the 43-kD protein. Torpedo dystrophin was also crosslinked at the same concentrations as were effective for the 43-kD protein and gamma subunit. On the basis of these results, we conclude that the 43-kD protein is intimately associated with the gamma subunit of AChR and Torpedo dystrophin. PMID- 1290461 TI - DNA polymerase alpha, beta, and gamma activities in human lymphocytes stimulated by Tora-mame (Phaseolus vulgaris) lectin. AB - We measured the levels of the DNA polymerases alpha, beta, and gamma in human peripheral lymphocyte cells stimulated with Tora-mame lectin (TM-lectin) and the induction patterns were compared to those with other plant lectins, i.e., phytohemagglutinin (PHA) and pokeweed mitogen (PWM). The maximum activity of DNA polymerase alpha in lymphocytes was achieved at the concentration of 10 micrograms/ml with TM lectin and the dose response curve of TM lectin showed a sharp peak in contrast to that of PWM. During prolonged stimulation for 10 days, the time course of DNA polymerase alpha induction was different among these three lectins. A peak of alpha-enzyme was correlated with maximal incorporation of [3H]thymidine and was observed on the fourth day with TM lectin, on the third day with PHA, and sixth day with PWM. DNA polymerase beta in lymphocytes was also activated by the addition of these proteins. Two different peaks were observed during a 10-day period with every lectin, and TM lectin was most potent stimulator among them. The activity of DNA polymerase gamma in lymphocytes was at a very low but detectable level which increased slightly in response to TM lectin treatment. Although some variability of gamma-enzyme activity was observed after the seventh day, the pattern in the course of 7 days was similar among the lectins. PMID- 1290463 TI - Acidic alpha-D-mannosidase in phenotypically different leukemic lymphoid cells. AB - The activity of acid alpha-mannosidase in phenotypically characterized lymphoid cells, isolated from peripheral blood, spleen and lymph nodes of patients with various lymphoproliferative disorders has been studied. Cells with different immunophenotypes were shown to have different alpha-mannosidase activity levels. The lowest alpha-mannosidase activity was observed in cells phenotypically corresponding to early B cells obtained from B-CLL patients. The highest activity was determined in cells with phenotypes of activated, CD11c-expressing B cells from B-NHL and HCL patients. There were considerable differences in alpha mannosidase activity between peripheral blood and spleen lymphoid cells of B-NHL patients with spleen damage. The data obtained may be used in classification, primary diagnosis and staging of hematopoietic malignancies. PMID- 1290464 TI - Role of alkaline metal ions in the H(+)-ATPase activity of various yeast species. AB - Saccharomyces cerevisiae, Schizosaccharomyces pombe, Endomyces magnussi, Lodderomyces elongisporus and Rhodotorula gracilis, yeast species ranging from a glycolytic type to a strictly aerobic one, were tested for the activity of their plasma membrane H(+)-ATPase and the effect of alkaline metal cations thereon. The ATP-hydrolyzing activity of membranes from glucose-activated cells ranged from 456 to 932 mumol inorganic phosphate released per min per 1 g membrane protein. The effect of 0.2 M Li+, Na+, K+, Rb+ and Cs+ never exceeded the statistical range of error. In contrast, acidification after glucose addition ranged from 0.15 (for R. gracilis) to 14.8 nmol H+ per min per mg dry weight (for S. cerevisiae) and it was markedly influenced by the presence of alkaline metal chlorides, the highest effect observed being a seven-fold increase by K+ in a S. cerevisiae suspension. The effects were additive to those observed without ions in solution and are ascribed to the operation of independent channels and/or exchange systems for H+ with a clear selectivity toward K+. The separate nature of the ion-triggered extracellular acidification is supported by a different ratio of titration to pH-derived acidity with and without K+. PMID- 1290466 TI - Oxidation of cystathionamine and lanthionamine by lentil seedlings amine oxidase. AB - Cystathionamine and lanthionamine are good substrates for lentil seedlings amine oxidase. One mole of hydrogen peroxide and one mole of ammonia per mole of substrate are produced, indicating that only one amino group is oxidized to aldehyde. The aminoaldehydes so originated undergo cyclization by intramolecular Schiff base formation. The pH optimum for the oxidation of either cystathionamine or lanthionamine is 7.0 in potassium phosphate buffer. The Km values are 0.61 and 0.84 mM respectively, similar to that for cystamine (0.8 mM). PMID- 1290465 TI - Lentil seedling amine oxidase: interaction with carbonyl reagents. AB - Carbonyl reagents containing a primary amino group were covalently bound by lentil seedling amine oxidase to resolve conflicting data for both the number of functional active sites in the dimeric enzyme. Active site titration of highly purified enzyme samples with all the carbonyl reagents extrapolates to 1 mol of inhibitor/mol of enzyme subunit indicating the presence of a cofactor at each enzyme subunit. This result is at variance with numerous previous reports of only one functional cofactor for enzyme dimer in copper amine oxidase. PMID- 1290467 TI - On the anomalous behaviour on gel-filtration and SDS-electrophoresis of prothymosin-alpha. AB - The regulator of T-cell proliferation prothymosin alpha, is a protein with a relative molecular mass of 12 KDa as calculated from its amino acid sequence. This immunoregulator exhibits anomalous behaviour on gel-filtration and SDS-PAGE electrophoresis appearing as oligomers which are 5 or 2 fold larger than the corresponding polypeptide. These results suggest that a dimeric form of prothymosin alpha is stable to dissociation by SDS and reduction by beta-mercapto ethanol. PMID- 1290468 TI - Complexes involving gossypol, DNA and Cu(II). AB - Gossypol, a polyphenolic binaphthyl dialdehyde found in cotton seeds, is a dietary mutagen and a potential male contraceptive. We have earlier shown that in the presence of Cu(II) gossypol causes strand breakage in double stranded DNA and that active oxygen species are involved in this reaction. In this paper we present experiments to suggest that gossypol may be oxidised by Cu(II) to a gossypol radical that may directly react with DNA. Changes in absorption spectrum and fluorescence emission spectrum of gossypol indicated that it binds to both double stranded and single stranded DNA. Gossypol and Cu(II) were shown to form a charge transfer complex that decayed in an oxygen independent reaction. The rate of DNA degradation by gossypol-Cu(II) complex was found to be the same both in the presence and absence of molecular oxygen. PMID- 1290469 TI - Dual hormonal involvement in the regulation of rat uterine collagenase activity. AB - Hormonal control of rat uterine collagenase activities which use collagen types I, III, and V as the substrates has been studied. The collagenases are shown to be regulated in general by estradiol as well as by progesterone. However, the enzyme activity that uses type III collagen as the substrate appears to have a preferential response to progesterone over estradiol. PMID- 1290470 TI - Downregulation of saturated fatty acid and upregulation of unsaturated fatty acid by 13-cis-retinoic acid in human prostate cancer cells. AB - Retinoids play a major role in regulation of epithelial cell growth and cellular differentiation, but their mechanism(s) of action are still unclear. In the present study, we examined the effects of 13-cis-retinoic acid (13-cis-RA) on cytotoxicity, growth properties, morphology, neutral lipids, phospholipids and fatty acids in cultured human prostate cancer cell lines. The results of these experiments suggest that 13-cis-RA (10 microM) inhibits the DNA synthesis and nude mice tumorigenicity by 2- to 3-fold, compared to control. Electron microscopy revealed more differentiated phenotypes after 13-cis-RA treatment. There was a significant increase in phosphatidylcholine and decrease in sphingomyelin in 13-cis-RA treated cells compared to control. The saturated fatty acids significantly decreased whereas unsaturated fatty acids were increased after 13-cis-RA treatment in prostate cancer cells. This study demonstrates for the first time that retinoic acid mediated downregulation of saturated fatty acids and upregulation of unsaturated fatty acid in human prostate cancer cells. PMID- 1290471 TI - Gonadotropin bioactivities in mouse, hamster, rat and guinea pig pituitaries are largely adsorbed on concanavalin A-sepharose. AB - The pituitaries of mice, hamsters, guinea pigs and rats were extracted with Tris Cl buffer and the extracts were chromatographed on Concanavalin A (ConA) Sepharose into unadsorbed ConA I and adsorbed ConA II fractions. The ConA I fraction was subjected to gel filtration on Sephadex G-100 and fractionated into an unretarded peak and several retarded peaks. The peak with a molecular weight of approximately 40,000 (designated ConAI Sephadex fraction II) was then subjected to ion exchange chromatography on CM-cellulose and fractionated into an unadsorbed CM I and an adsorbed CM II fraction. The ConA II fraction was fractionated by ion exchange chromatography on CM-cellulose into CM I and CM II fractions. The ConA II CM II fraction was the chromatographic fraction which exhibited the highest potency in stimulating testosterone production by isolated rat Leydig cells. Its activity was much higher than the corresponding ConA I Sephadex fraction II CM II fraction which differed chromatographically only by non-adsorption on ConA-Sepharose. The ConA II CM II fraction manifested cross reactivity in a rat luteinizing hormone (LH) radioimmunoassay. The guinea pig pituitary ConA II CM II fraction also cross-reacted in a rat thyroid stimulating hormone radioimmunoassay. The ConA II fractions of hamster and guinea pig pituitary extracts demonstrated follicle stimulating hormone (FSH) activity while the corresponding ConA I fractions did not. The results suggest that the ConA II/ConA II CM II fraction contained most of the FSH and LH activities present in the pituitary extract. PMID- 1290472 TI - Renal insensitivity to atrial natriuretic peptide in patients with cirrhosis and ascites. Effect of increasing systemic arterial pressure. AB - The IV infusion of pharmacological doses (0.05 microgram.kg-1.min-1) of atrial natriuretic peptide to 16 patients with cirrhosis and ascites induced a significant increase in sodium excretion (65 +/- 23 to 517 +/- 231 mu Eq/min), urine volume (10.7 +/- 2.3 to 15.7 +/- 3.7 mL/min), and glomerular filtration rate (89 +/- 4 to 110 +/- 4 mL/min) in only 5 patients (responders). No significant changes in these parameters (15 +/- 6 to 11 +/- 4 mu Eq/min, 5.5 +/- 1.0 to 4.2 +/- 1.1 mL/min, and 81 +/- 5 to 79 +/- 6 mL/min, respectively) were observed in the remaining patients (nonresponders). Compared with responders, nonresponders had significantly lower baseline sodium excretion (P less than 0.02), urine flow (P less than 0.05), free water clearance (2.5 +/- 0.9 vs. 6.9 +/- 2.1 mL/min; P less than 0.05), and mean arterial pressure (82 +/- 3 vs. 96 +/ 2 mm Hg; P less than 0.01) and significantly higher plasma renin activity (16.3 +/- 4.9 vs. 1.8 +/- 0.2 ng.mL-1.h-1; P less than 0.05) and aldosterone level (99 +/- 24 vs. 13 +/- 2 ng/dL; P less than 0.05). Atrial natriuretic peptide produced a similar reduction of arterial pressure in both groups. To investigate whether the blunted natriuretic response to atrial natriuretic peptide in nonresponders was caused by their lower arterial pressure, atrial natriuretic peptide was infused in 7 of these patients after increasing their arterial pressure to the levels of responders with nonrepinephrine. The increase in arterial pressure (from 81 +/- 5 to 95 +/- 5 mm Hg), which was not associated with significant changes in plasma renin activity and aldosterone concentration, did not reverse the blunted renal response to atrial natriuretic peptide in any of these patients. These results indicate that cirrhotic patients with blunted renal response to atrial natriuretic peptide are characterized by low arterial pressure, marked overactivity of the renin-aldosterone system, and severe sodium and water retention. Correction of hypotension without increasing effective blood volume does not restore renal insensitivity to atrial natriuretic peptide. PMID- 1290473 TI - A controlled assessment of direct intraperitoneal insemination. AB - OBJECTIVE: To test the efficacy of direct intraperitoneal (IP) insemination and its effect on cell-mediated immunity. DESIGN: A prospective trial with each couple having one treatment (insemination) cycle and one control (timed intercourse) cycle performed in random order with the same ovulation stimulation in both cycles. SETTING: Secondary and tertiary referral fertility clinics; university teaching hospital. PATIENTS: Twenty-six infertile couples. Excluding pregnancy, only one couple did not complete the two cycles. INTERVENTIONS: Ovulation induction in both cycles. Intraperitoneal insemination in the insemination cycles. MAIN OUTCOME MEASURES: These were pregnancy rate (treatment versus control) and mixed lymphocyte response (MLR) sensitivity (before and after direct IP insemination treatment). RESULTS: There were four control and no treatment pregnancies. This was not a significant difference (odds ratio). Mixed lymphocyte responses in fertile subjects did not change during the menstrual cycle (Wilcoxon). There was no significant increase in MLR sensitivity to partner's cells after direct IP insemination treatment. CONCLUSIONS: This controlled study found no benefit from direct IP insemination in terms of pregnancies over control cycles. There was no evidence that direct IP insemination had increased cell-mediated immune response sensitivity to husband's cells. PMID- 1290474 TI - Autoantibodies to nuclear lamin C in the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. AB - OBJECTIVE: To examine the autoantibodies (antinuclear antibodies [ANA]) present in serum from a patient with eosinophilia-myalgia syndrome (EMS). METHODS: Sera obtained during the early phase of EMS and following therapy with prednisone were screened by indirect immunofluorescence on HEp-2 cells, and ANA were characterized by immunoblotting on a purified nuclear lamin fraction. RESULTS: ANA with a ring-like pattern of nuclear staining were identified at high titer by immunofluorescence, and immunoblotting experiments showed them to be directed against lamin C. The antibody titer declined dramatically after discontinuation of L-tryptophan and therapy with prednisone. CONCLUSION: This is the first characterization of an antigen/autoantibody system associated with EMS. The findings indicate that this EMS-associated autoantibody recognizes epitopes localized in the carboxyterminal region of lamin C. The occurrence of anti-lamin C autoantibodies in one EMS patient expands the spectrum of clinical conditions associated with these antibodies, and provides evidence for an autoimmune response in EMS. PMID- 1290475 TI - Placebo-controlled trial of ulcerative colitis with oral 4-aminosalicylic acid. AB - Forty patients with active ulcerative colitis were randomly assigned to receive either 4 g of oral enterically coated 4-aminosalicylic acid (para-aminosalicylic acid) or placebo. The duration of treatment was 12 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histological inflammation in rectal biopsy specimens. At 12 weeks, 11 of 20 patients (55%) who received 4-aminosalicylic acid showed improvement in clinical and sigmoidoscopic variables. In contrast, only 1 of 20 patients (5%) who had received placebo showed improvement (P less than 0.005). Eighteen of the 19 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid. Of the 18, 11 showed clinical and sigmoidoscopic improvement. Patients allergic or intolerant to sulfasalazine with extensive disease were more likely to respond to 4 aminosalicylic acid. PMID- 1290476 TI - Threatened survival of academic-based genetic laboratory services. PMID- 1290477 TI - A living retained second twin 4 days after the first. PMID- 1290478 TI - Tricorrectional bunionectomy for surgical repair of juvenile hallux valgus. AB - The authors propose the use of the tricorrectional bunionectomy as an alternate correction of severe deformity in juvenile hallux valgus. In the past, hallux valgus surgery in juveniles has been avoided. A follow-up study of the tricorrectional bunionectomy as the surgical treatment for juvenile bunion deformity in seven patients is presented. PMID- 1290479 TI - Granuloma annulare of the penis. AB - Granuloma annulare is an uncommon skin condition, most often found on the extremities of young females. A case of granuloma annulare occurring on the penis of a 61 year old man is reported and the current literature associating granuloma annulare and conditions likely to present to genitourinary clinics is reviewed. PMID- 1290480 TI - Successful reintroduction of methotrexate after pneumonitis in two patients with rheumatoid arthritis. AB - Two patients are described with severe and progressive rheumatoid arthritis in whom methotrexate was reintroduced despite previous methotrexate related pneumonitis. In both patients a marked improvement in disease control occurred without a recurrence of the pneumonitis. PMID- 1290481 TI - Cutaneous graft-versus-host-like reaction after paternal lymphocyte immunization for prevention of recurrent abortion. AB - We have presented an immunocompetent patient who, after paternal lymphocyte immunization, developed a GVH-like skin reaction; she recovered spontaneously. This complication is rarely seen. This was the only case observed in our series of over 70 patients immunized. A similar phenomenon was not reported in a larger series by Carp and colleagues (1). However, the case deserves special attention because this reaction can be life-threatening. Therefore, we suggest that paternal lymphocyte immunization should be recommended only for those patients who have undergone a thorough work-up and in whom all causes, other than immunological, for recurrent abortion have been excluded. Even then, this treatment should be given with utmost caution. In view of the above described complication, we believe that more data are still required to justify offering such a treatment modality on a routine basis. PMID- 1290482 TI - Nutritional implications of fat substitutes. AB - The possibility of replacing fats in foods through the use of alternative ingredients has generated substantial interest among food industry and nutrition professionals as well as among the lay public and news media. However, even in academic circles, there is a tendency to consider "fat substitutes" as a homogeneous group, when they are not, and also to make unproven assumptions regarding their likely efficacy in reducing fat intake and aiding in maintenance of appropriate energy balance. Governmental and industrial bodies have tended to place much greater emphasis on the potential risks of these materials than on their possible benefits. A reasoned consideration of the nutritional implications of fat substitutes examines what these materials are, how they might be used, and how they might affect eating behavior and nutritional status in the general population. The existing literature suggests that although the risks of existing and proposed fat substitutes are probably limited, their nutritional benefits are largely unproven. PMID- 1290483 TI - Is it time again for patient selection criteria? PMID- 1290484 TI - Duration of MDT for paucibacillary leprosy. PMID- 1290485 TI - Symptomatic chronic paroxysmal hemicrania. AB - A patient with chronic paroxysmal hemicrania (CPH) associated with a gangliocytoma growing from within the sella turcica is reported. This tumor displaced the floor of the third ventricle and surrounded the internal carotid artery on the same side as the headache. Partial removal of the tumor followed by radiation resulted in amelioration of headache. The anatomical location of the tumor and its possible relationship to the pathogenesis of CPH is discussed. PMID- 1290486 TI - Health care injustice fuels rage, riots. PMID- 1290487 TI - Violence in America: a public health emergency. Time to bite the bullet back. PMID- 1290489 TI - Numbering the North's medical events: humanitarianism and science in Civil War statistics. PMID- 1290490 TI - Clinical diagnostic criteria for TMD. New classification permits multiple diagnoses. AB - One of the first to permit multiple diagnoses, this new TMD classification scheme offers guidelines for clinicians and those conducting clinical field studies. The scheme was applied to a TMD population, with control subjects. PMID- 1290488 TI - Thrombin-specific inhibition by and slow cleavage of hirulog-1. AB - Hirulog-1 [D-Phe-Pro-Arg-Pro-[Gly]4-desulphohirudin-(53-64) (HV1)] was designed to bind by its first four and last 12 residues to the alpha-thrombin catalytic site and anion-binding exosite for fibrin(ogen) recognition respectively, with a [Gly]4 bridge and an Arg-Pro bond at the scissional position. Human alpha-, gamma and zeta-thrombins, as well as bovine trypsin, readily hydrolyse Spectrozyme-TH (D-hexahydrotyrosyl-Ala-Arg p-nitroanilide) at pH 7.4 and approx. 23 degrees C. Both alpha- and zeta-thrombins, which have high fibrinogen-clotting activities (greater than 3000 kunits/g), were inhibited with this substrate by hirulog-1 [Ki = 2.56 +/- 0.35 nM (n = 3) and 1.84 +/- 0.15 nM (n = 3) respectively] and slowly cleaved the inhibitor [k = 0.326 +/- 0.082 min-1 (n = 12) and 0.362 +/- 0.056 min 1 (n = 18) respectively], whereas gamma-thrombin, which has essentially no clotting activity (approx. 4 kunits/g), and trypsin were not inhibited with greater than 1000-fold molar excess of hirulog-1. Similar inhibition parameters were also obtained for hirulog-1 incubated with alpha-thrombin or zeta-thrombin at approx. 23 degrees C and by measuring thrombin activity with fibrinogen in the clotting assay at 37 degrees C. Cleavage of the Arg-3-Pro-4 bond in hirulog-1 by either alpha- or zeta-thrombin was shown by identical cleavage products of either thrombin on h.p.l.c. and by sequence analysis of the alpha-thrombin products. These data demonstrate that hirulog-1 is a specific inhibitor of thrombin forms with high fibrinogen-procoagulant activities and that its Arg-3-Pro-4 bond is slowly cleaved by these thrombin forms. PMID- 1290491 TI - Findings of the NCEPOD report for 1990. PMID- 1290492 TI - The prognostic value of serum troponin T in unstable angina. AB - BACKGROUND: Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. METHODS: We screened 109 patients with unstable angina (25 with accelerated or subacute angina and 84 with acute angina at rest) for serum creatine kinase activity, creatine kinase isoenzyme MB activity, and troponin T every eight hours for two days after admission to the hospital. The outcomes of interest during the hospitalization were death and myocardial infarction. RESULTS: Troponin T was detected (range, 0.20 to 3.64 micrograms per liter; mean, 0.78; median, 0.50) in the serum of 33 of the 84 patients (39 percent) with acute angina at rest. Only three of these patients had elevated creatine kinase MB activity (two were positive for troponin T, and one was negative). Of the 33 patients who were positive for troponin T, 10 (30 percent) had myocardial infarction (3 after coronary-artery bypass surgery), and 5 of these died during hospitalization. In contrast, only 1 of the 51 patients with angina at rest who were negative for troponin T had an acute myocardial infarction (P less than 0.001), and this patient died (P = 0.03). Thus, 10 of the 11 patients with myocardial infarctions had detectable levels of troponin T; only 1 had elevated creatine kinase MB activity. Troponin T was not detected in any of the 25 patients with accelerated or subacute angina, and none of these patients died. CONCLUSIONS: Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial-cell injury than serum creatine kinase MB activity, and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina. PMID- 1290493 TI - Hemisphericity and self-esteem. AB - The 1991 paper by Persinger and Makarec, while posing some interesting theoretical and speculative questions, misstates the magnitude of the effect size in the validation of the Hemisphericity Questionnaire and draws some unwarranted conclusions. This article briefly reviews the issues involved. PMID- 1290494 TI - Gram scale purification and preparation of rabbit liver zinc metallothionein. AB - A simplified procedure for purifying gram quantities of rabbit liver metallothionein (MT) using gel filtration and anion exchange chromatography is presented. The MT purification made use of anion exchange batch elution chromatography which greatly shortened the procedure. Quantitation techniques for use with crude and purified MT are discussed. This paper also describes the preparation of large amounts of ZnMT from Cd,ZnMT. PMID- 1290496 TI - Gas mask phobia. PMID- 1290495 TI - The association of AIDS education and sex education with sexual behavior and condom use among teenage men. AB - According to a 1988 nationally representative survey, most 15-19--year-old men in the United States have received formal instruction about AIDS (73%), birth control (79%) and resisting sexual activity (58%). Results of multivariate analyses show the receipt of AIDS education and sex education to be associated with modest but significant decreases in the number of partners and the frequency of intercourse in the year prior to the survey. Having received instruction in these topics was also associated with more consistent condom use. Instruction in some topics was associated with increases in knowledge and attitudes about AIDS, but these increases were not always correlated with safer behavior. PMID- 1290497 TI - Acute gastroenteritis in children. AB - Despite the great advances in modern medicine, children still die from dehydration due to acute infectious gastroenteritis. These deaths are almost always preventable by using rehydration fluids. This article focuses on assessment and treatment of the affected patient. PMID- 1290498 TI - Working party report on cardiac rehabilitation. PMID- 1290499 TI - Updates primary care for asymptomatic HIV patients. PMID- 1290500 TI - Saliva as a diagnostic fluid. PMID- 1290501 TI - Women prefer hospital births. PMID- 1290502 TI - Frequency of citation and outcome of cholesterol lowering trials. PMID- 1290503 TI - Reprocessing data to form QALYs. PMID- 1290504 TI - Diets that protect against coronary heart disease. PMID- 1290505 TI - Women's preference for place of birth. PMID- 1290506 TI - Saliva as a diagnostic fluid. PMID- 1290507 TI - A&E consultants must remain on the shop floor. PMID- 1290508 TI - Vein graft stenosis. PMID- 1290509 TI - Studies on the effect of tunicamycin on erythrocytic stages of Plasmodium falciparum. PMID- 1290510 TI - Cholesterol gallstones and aspirin. PMID- 1290511 TI - Granuloma annulare of the penis. PMID- 1290512 TI - Bone cancer risk estimates. AB - Due to confusion between endosteal (bone surface) dose and average skeletal dose, ICRP 60 has substantially overestimated the risk of radiogenic bone cancer. This confusion apparently stems from an incorrect reading of the BEIR IV report, which does not clearly draw this distinction. It should also be noted that what appear to be summary numerical risk estimates for bone sarcoma induction in BEIR IV and BEIR V refer only to average skeletal dose as calculated for 224Ra. PMID- 1290513 TI - Percutaneous injuries. PMID- 1290514 TI - BMIPP in hypertrophic cardiomyopathy. PMID- 1290515 TI - Kaposi's sarcoma, rheumatoid arthritis and immunosuppressive and/or corticosteroid therapy. PMID- 1290516 TI - Comment: nasal myiasis in leprosy. PMID- 1290517 TI - Radiological investigation of urinary tract infection in children. PMID- 1290519 TI - ESRD program fiscally fit compared to others. PMID- 1290518 TI - Metabolic disturbances in AIDS. PMID- 1290520 TI - Physicians should have their own selection criteria. PMID- 1290521 TI - Intraoperative angiography and temporary balloon occlusion of the basilar artery as an adjunct to surgical clipping: technical note. PMID- 1290522 TI - OR disposables vs. reusables: a debate. PMID- 1290523 TI - Blindness after blepharoplasty. PMID- 1290524 TI - Sequence discrimination by alternatively spliced isoforms of a DNA binding zinc finger domain. AB - Two major developmentally regulated isoforms of the Drosophila chorion transcription factor CF2 differ by an extra zinc finger within the DNA binding domain. The preferred DNA binding sites were determined and are distinguished by an internal duplication of TAT in the site recognized by the isoform with the extra finger. The results are consistent with modular interactions between zinc fingers and trinucleotides and also suggest rules for recognition of AT-rich DNA sites by zinc finger proteins. The results show how modular finger interactions with trinucleotides can be used, in conjunction with alternative splicing, to alter the binding specificity and increase the spectrum of sites recognized by a DNA binding domain. Thus, CF2 may potentially regulate distinct sets of target genes during development. PMID- 1290525 TI - Conclusions on cancer and low socioeconomic status questioned. PMID- 1290527 TI - Electrical dosage and efficacy in ECT. PMID- 1290526 TI - Difficulties of diagnosing testicular tumours. PMID- 1290528 TI - Nonlinear pharmacokinetics in critically ill patients. PMID- 1290529 TI - Capacitated or acrosome-reacted sperm. PMID- 1290530 TI - Estimating cumulative pregnancy curves. PMID- 1290531 TI - Relationship between colorectal neoplasia and primary sclerosing cholangitis in ulcerative colitis. PMID- 1290532 TI - A replication study of staff injuries in a state hospital. PMID- 1290533 TI - Drug-induced liver injury. PMID- 1290534 TI - In situ localization of IgG in epidermolysis bullosa acquisita by immunogold technique. PMID- 1290535 TI - Methemoglobinemia resulting from an unusual treatment for costochondritis. PMID- 1290536 TI - Duration of MDT for paucibacillary leprosy. PMID- 1290537 TI - Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. AB - Patients currently suffering or recently recovered from chronic fatigue syndrome (CFS) were compared with each other and with a group of well-matched controls in a study of diurnal variation in levels of perceived mental and physical energy and positive and negative affect. Patients who were currently ill showed diurnal variation in patterns of energy, with maximum levels being recorded between 10.00 h and 12.00 h which were significantly higher (P < 0.05) than energy levels recorded on rising or retiring. This pattern was similar to the controls but average energy levels at each time point were lower (P < 0.05) among the ill patients. Recovered patients showed the same pattern, with mean energy levels falling between those of the ill patients and controls. Similar diurnal patterns were found for perceptions of positive, though not negative affect. Correlations between physical and mental energy and between both of these energy variables and positive affect were high (r = 0.75 to 0.85) in both controls and CFS patients. However, correlations with negative affect were low (eg r = -0.10) and non significant. Total scores on the Hospital Anxiety and Depression Scale (HAD) were significantly higher (P < 0.05) among patients who were still ill than those who had recovered. Scores on the HAD Depression (but not Anxiety) subscale were also significantly higher among those who were still ill (P < 0.01). These findings may be of value in facilitating programmes of cognitive-behavioural modification intended to aid the recovery of patients with CFS. PMID- 1290538 TI - Low dose botulinum toxin for spasmodic torticollis. PMID- 1290539 TI - Psychological distress and breast cancer screening among women at high risk: where are we? PMID- 1290540 TI - Re: Balloon ureteral occlusion: a new reversible technique in the management of ureteral fistulas. PMID- 1290541 TI - Duplex ultrasound criteria for diagnosis of splanchnic artery stenosis or occlusion. PMID- 1290542 TI - Violence in America: time to bite the bullet back. PMID- 1290543 TI - Complete transposition of the great arteries with aortopulmonary window. PMID- 1290544 TI - Observations on the development of T-cell leukaemia in the patient successfully treated by interferon-alpha for typical hairy cell leukaemia (HCL) PMID- 1290545 TI - The management of terminally ill patients. PMID- 1290546 TI - Frozen thawed blood stored at -20 degrees C to -25 degrees C. PMID- 1290547 TI - The management of terminally ill patients. Ethics of Clinical Practice Subcommittee, Ethics Review Committee, Central Sydney Health Service. PMID- 1290548 TI - Effects of spinal flexion and extension exercises on low-back pain and spinal mobility in chronic mechanical low-back pain patients. PMID- 1290549 TI - Veterinary nurse training. PMID- 1290550 TI - Acid-base disorders revisited. PMID- 1290551 TI - Algodystrophy after kidney grafting. PMID- 1290552 TI - Re: "Tiger's-eye pneumoconiosis". PMID- 1290553 TI - Do-not-resuscitate orders in the emergency department. PMID- 1290554 TI - Regional and systemic oxygen delivery/uptake relations and lactate flux. PMID- 1290555 TI - A proposed trial of amiodarone for atrial fibrillation. PMID- 1290556 TI - D-penicillamine and rheumatoid factor. PMID- 1290557 TI - Pancreatic resection versus peritoneal lavage in acute necrotizing pancreatitis. PMID- 1290558 TI - The paradoxical anticonvulsive and awakening effect of high-dose pyridoxine treatment for isoniazid intoxication. PMID- 1290559 TI - Male homosexuality. PMID- 1290560 TI - Joel McKeith Dalrymple (1939-1992) PMID- 1290561 TI - Drinking water fluoridation and caries prophylaxis: with special consideration of the experience in the former East Germany. AB - Drinking water fluoridation for caries prophylaxis is not a means of primary prevention: i.e., avoidance of sugar and microorganisms in the oral cavity; but rather a means of secondary prevention: e.g., prevention of bacterial production of carboxylic acid from sugar, and therapy: e.g., enhancement of enamel resistance to demineralization by incorporation of fluoride in remineralization of the enamel surface. Currently available epidemiologic studies on the effects of drinking water fluoridation reveal: reduction of the incidence of caries, particularly in children no detrimental health effects; cosmetically undesirable dental fluorosis may occur, however. Nevertheless, introduction of drinking water fluoridation in Germany is not recommendable because of: the greater effectiveness of primary caries prevention, the acceptance of which is reduced, however, by drinking water fluoridation the at least equal prophylactic effect of fluoride via other routes, e.g. via toothpaste the narrow range between beneficial and detrimental dosage the avoidance of fluoride-enriched waste water the prerogative of minimal manipulation of drinking water content. PMID- 1290562 TI - [Mercury exposure of the population. IV. Mercury exposure of male dentists, female dentists and dental aides]. AB - Urinary mercury levels were determined in 22 dentists and 46 dental nurses and assistants working in 15 private dental offices in West-Germany. For comparison, urinary mercury levels of 29 subjects without occupational mercury exposure were studied. On average, urinary mercury in dental personnel was higher than in the reference group. Individual mercury levels, however, were all significantly below present occupational exposure limits. Urinary mercury was significantly correlated with the number of amalgam fillings in dental personnel as well as in the reference group. Following administration of Dimaval a significant increase of mercury excretion was observed in both groups. Regarding total exposure to mercury in dental personnel, the contribution of mercury exposure from the occupational environment is of the same order of magnitude as their exposure from their own amalgam fillings. Dental nurses were found to be more exposed than dentists. This finding seems to be related predominantly to the larger number of amalgam fillings in dental nurses. PMID- 1290563 TI - Trace elements in the human blood, cerebrospinal and amniotic fluid. AB - Human biological samples using the atomic emission method. The concentration of 27 micro- and macro elements was specified in a total number of 1221. Some of the patients tested were under hospital treatment because of chronic disease (727 persons), others were blood donors (71 persons) or pregnant women and newborn infants (107-107 persons, respectively). In the serum samples of the tested persons the concentration of barium, mercury, nickel and gallium showed characteristic differences. Concentrations of many micro elements in the serum and cerebrospinal fluid changed with age and sex. The tendency becomes characteristic after the age of 45 and 60, respectively. The concentration of elements in the blood serum of mothers and their newborn infants seems to be nearly identical with a considerable deviation observed only in case of aluminum, barium and iron (significant difference). The detected elements can pass through the placenta. This particularly applies to lead because the average lead concentration in the serum of newborn infants is 159 micrograms/litre even at birth. PMID- 1290564 TI - [Biological safety investigations of the production of human insulin by genetically engineered E. coli K-12 cells. 1. Survival capacity of the production strain in the digestive tract of Gottinger miniature swine]. AB - The residence time of genetically engineered Escherichia coli K-12 cells in the digestive tract was tested by feeding Gottinger minipigs 10(10)-10(11) cells of strain W3110iqM15 (pSW3). This strain is a production strain for human insulin and carries the plasmid pSW3 which contains the genes for human insulin. The test strain could be selected as white colonies grown on McConkey ampicillin plates and could be identified by complementation analysis due to its lacZ M15 deletion. The strain could be isolated from the faeces of the animals up to 72 h after feeding, thereafter no cells of the phenotype of the test strain grew on McConkey ampicillin plates. So the production strain for human insulin W3110iqM15 (pSW3) was not able to colonize the digestive tract of the Gottinger minipig. Feeding the genetically engineered E. coli K-12 cells had no influence on the welfare of the animals. PMID- 1290565 TI - [PATIS--a questionnaire-based, PC-assisted patient information system in the field of environmental medicine]. AB - PATIS was developed as a questionnaire-based, PC-assisted patient-information- and documentation-systems within the framework of the "Umweltmedizinische Beratungsstelle" (advisory board for clinical environmental medicine) at the Medical Institute of Environmental Hygiene at the Heinrich-Heine-University Dusseldorf. PATIS is a substantial element of a planed knowledged-based-system in environmental medicine. This system will further-more consist of databases for chemical substances information, exposition, and literature. PATIS records information about patients concerning personal data, former diseases, symptomatology and complaints, lifestyle, residential and working area, and spare time activities. Furthermore the state of physical examination, performances of diagnostics, and laboratory investigations are documented. A different questionnaire exists for children younger than 12 years. PATIS is able to supply an automatic report based on information of the questionnaire. This system is realized in the relational-database-system dBase IV and is utilized practice since the beginning of 1991. PMID- 1290566 TI - [The danger of infection in inhalation rooms]. AB - There are alarming reports about high counts of Legionella and Pseudomonas in the aerosol of inhalation-rooms. We therefore investigated 14 institutions (6 kurhauses, 5 hospitals and 3 sanatoria for children) in Schleswig-Holstein, each of them at least five-fold. For that purpose the inhalant (seawater as a rule) was investigated for the total bacterial number and the number of Legionella. Cfu/m3 air were determined at the aerosol outlet and a qualitative search for Legionella was done in the piping. In addition bacterial numbers in the air at the breathing-levels of patients were measured in order to be able to assess health hazards by germs of other patients. Detected bacterial numbers (10(1) - > 10(4)) were basically subject to the handling of the equipment and the type of apparatus used. Predominantly Staphylococci and Bacilli were found and above all when the first row of investigations was carried out large numbers of Pseudomonas, Aeromonas and others occurred. Legionella could not be detected. As a whole the investigations showed that properly maintained room-inhalators pose no higher risk of infection. These facilities, however, might be contaminated at any time and there is a certain--even though comparatively low--risk of infection due to germs exhaled by other patients. Patients, which are predisposed to infections of the respiratory tract--f.i. patients suffering from mucoviscidosis or patients with lowered resistance--should therefore generally use single inhalators. PMID- 1290567 TI - [Long-term study of the persistence of E. coli in waters of different composition]. AB - The survival of E. coli ATCC 11229 at different initial concentrations was determined in water of standardized hardness, in tap water from Kiel and in groundwater from the Segeberger forest with pH-values of 4.5, 6.9 and 8.5. In groundwater at pH 4.5 the bacteria died relatively soon, whereas otherwise in relation to the test conditions long persistence times have been determined. The persistence of E. coli in tap water from Kiel and in water of standardized hardness differed from that in groundwater with comparable pH-values of pH 6.9 and pH 8.5. In groundwater the colony forming units generally decreased slightly, whereas in tap water and in water of standardized hardness high initial bacterial concentrations resulted in growth, low ones on the other hand in a decrease of the colony forming units. In the area of middle initial bacterial concentrations a significant growth of E. coli (frequently not before 50 days) as well as a die off could be observed in parallel samples. The influence of the water volume of the sample and the conditioning of the bacteria (unwashed - washed) were of secondary importance. PMID- 1290568 TI - Ring volume/ring liner ratio and effective setting expansion. AB - Effective radial setting expansion of wax patterns in a gypsum-bonded investment is influenced by many factors, especially by the diameter of the cylindrical casting ring. The hypothesis tested was that the ratio of the volume of the casting rings to the volume of the ring liner is a primary determinant of radial setting expansion. Mesio-occlusodistal inlay wax patterns were invested individually in plastic casting rings of different lengths and diameters and imaged using xeroradiography. Effective setting expansion was determined in 34-mm long, 28-mm-diameter rings and used as a predictor of expansion in rings of different sizes. Experimental setting expansion results did not differ significantly from the predicted values. PMID- 1290569 TI - Compressive strength of two modern all-ceramic crowns. AB - This study investigated the compressive strength of all-ceramic crowns manufactured using two recently introduced systems. The mean forces of fracture were 964 N for In-Ceram crowns, 814 N for paint-on IPS Empress crowns, and 750 N for layered IPS Empress crowns, compared with 1,494 N for metal ceramic crowns veneered on a nickel-chromium coping. The results indicate that clinical testing of these all-ceramic crowns is reasonable. Controlled, clinical, long-term evaluation is necessary to assess the safe application of these new crown systems. PMID- 1290570 TI - Longitudinal electromyographic study of chewing patterns in complete-denture wearers. AB - A longitudinal electromyographic study of the anterior temporal and masseter activity during habitual chewing of apple was performed on 21 subjects provided with immediate complete dentures. At the pretreatment stage, when the patients having an anterior residual dentition were chewing, the peak mean voltages showed low values (range, 48 to 58 microV). After denture placement, there was a further decrease of the temporal activity that persisted to the 6-month stage. After the dentures were relined, a significant increase in chewing force of the temporal muscles was noted at the 1-year stage. During the second year, when no corrections of the dentures were made, the temporal activity decreased below the pretreatment level. The masseter muscle chewing activity generally showed no significant changes during the 2-year observation period. The mean durations of the chewing strokes and chewing cycles were longer than values reported in dentate samples and generally displayed no significant changes during the 2-year period. PMID- 1290571 TI - The effect of five investing techniques on air bubble entrapment and casting nodules. AB - Five different investing techniques were used to invest lost-wax casting patterns. The use of an investing technique that subjects the invested casting ring to air pressure (40 lb per square inch) during setting was found to produce less air bubble/cast nodule incidence than did the other four techniques investigated. Not all cast nodules can be seen by the unaided eye; magnification is needed. More cast nodules than air bubbles were seen at the interface of pattern and investment, showing that there may be many air bubbles below the investment surface that are entered by the incoming alloy during casting. The effect of a surface-tension reducing (STR) agent on the air bubble incidence between pattern and investment depends on the investing technique used, although all techniques used showed a reduction in cast nodule incidence when an STR agent was used. Sprue direction was also found to influence the incidence of casting nodules. PMID- 1290572 TI - Effects of topical fluorides and citric acid on overglazed and autoglazed porcelain surfaces. AB - The effect of 1.23% acidulated phosphate fluoride, 0.40% stannous fluoride gels, and 2.00% citric acid solution on 150.00 overglazed and 150 autoglazed porcelain surfaces was measured using a profilometer. Application of 1.23% acidulated phosphate fluoride for periods of 16 and 32 minutes caused etching in both groups, but the autoglazed group was significantly more effected. In both groups increase in application time did not affect the amount of etching. No etching was detected in either group after the application of 0.40% stannous fluoride for 6 and 12 hours and 2.00% citric acid for 4 and 8 hours. PMID- 1290573 TI - Incisal-edge strength of porcelain laminate veneers restoring mandibular incisors. AB - Porcelain laminate veneers can be used to increase incisal-edge length. The purpose of this study was to determine the fracture resistance of porcelain veneer restorations on Cymel 1077 mandibular incisors that were incisally reduced 0.0, 0.5, 1.0, and 2.0 mm. Variables studied were incisal-edge length and the angle of applied force. Sixty-one porcelain laminate veneers were made to restore incisal-edge length and bonded to the prepared teeth. Samples were fractured at force angles of 130 degrees and 137 degrees. No significant difference was found between varying incisal-edge lengths (P > .05). However, the lower applied angle required greater average force to fracture (P = .005) as tested by ANOVA. PMID- 1290574 TI - A clinical evaluation of ceramic laminate veneers. AB - The objective of this study was to make a clinical quality evaluation of resin bonded ceramic veneers placed in general practice. Ceramic veneers were evaluated by four independent examiners according to the California Dental Association guidelines for evaluation of dental care. In addition, bleeding and margin index and mode of tooth preparation were recorded. None of the veneers had been replaced and only two had fractured. Almost all veneers received a satisfactory rating regarding surface, color, and margin integrity. More than half of the veneers had a satisfactory anatomical form. The bleeding index was comparable to that reported for other types of crowns. An equigingival or subgingival margin was most common. PMID- 1290575 TI - Guidelines for developing a dental laboratory infection-control protocol. AB - Guidelines for developing a dental laboratory infection-control protocol are discussed. A detailed outline of infection-control protocol regarding universal precautions, personal protective equipment, hepatitis B vaccination, environmental and surface cleaning and disinfection, and personnel training is presented. PMID- 1290576 TI - The effect of the mandibular buccal denture base surface on food retention. AB - The accumulation of food debris in the buccal vestibule surrounding a mandibular denture flange was studied. This investigation focused on the effect of the thickness, physiologic molding, and slope of the buccal flange of denture base on the patient's ability to expel test-food particles from the area. Experimental denture bases were placed in the mandibular buccal vestibule of subjects having a complete natural dentition. Only the slope of the polished surface of buccal flange was found to have a significant positive correlation with the ability to expel test food from the buccal vestibule. PMID- 1290577 TI - The effect of venting on the strength of Dicor and Hi-Ceram ceramic crowns. AB - Research has shown that external venting improves the marginal fit of cast crowns by decreasing hydrostatic pressure during seating. In turn, improving marginal fit has been shown to increase the strength of castable glass and other porcelain systems. This study evaluated the effect on the compressive strength of crowns with vent holes placed during and after fabrication. Forty-five artificial crowns were made from each material and divided into three equal groups: (1) crowns without vent holes, (2) crowns with a vent hole placed before casting, and (3) crowns with a vent hole placed using a rotary diamond instrument after casting. Standardized crowns were acid etched, silane treated, and filled with epoxy resin to provide a support base for testing. The crowns were then loaded to failure. One-way analysis of variance showed a significant difference among groups. Scheffe's Multiple Comparison Test was used for discrimination. The Dicor unaltered and fabricated vent group and the Hi-Ceram unaltered group had significantly higher resistance to fracture. PMID- 1290578 TI - Shear resistance of silver- and stainless steel-reinforced glass-ionomer cements bonded to enamel and dentin. AB - The shear bond strength to human dentin and enamel was evaluated for four glass ionomer cements: an experimental stainless steel-reinforced glass-ionomer cement, two commercially available silver-reinforced cements, and a conventional glass ionomer cement. Bonded specimens were stored in distilled water for 7 days during which time they were subjected to thermocycling in water baths at 5 degrees C and 55 degrees C for a 1-minute dwell time per bath and 1500 cycles. Specimens were then shear tested. The experimental stainless steel-reinforced glass-ionomer cement had a significantly higher bond strength to enamel (P < .01) and dentin (P < .05) than did the commercially available cements. PMID- 1290580 TI - Protocol for rt-Pa and streptokinase. PMID- 1290579 TI - Fracture-surface analysis of a glaze-strengthened magnesia core material. AB - The purpose of this research was to study fracture initiation in a glaze strengthened magnesia ceramic substance used as a core material for all-ceramic crowns. The fracture surfaces of modulus of rupture bars were studied to locate the fracture initiation point. These points were located at the center of hackles that are oriented parallel to the direction of the crack advance. The distance from the fracture initiation point to the surface of the test bars was measured. A direct relationship was found between the flexure strength and the depth of the fracture initiation point. This is consistent with the theory that residual compressive stresses at the glaze-body interface inhibit the spread of flaws and are responsible for the increases in strengths observed. PMID- 1290581 TI - Chronic heart failure and quality of life: the impact of nursing. AB - Chronic heart failure has been called the final common pathway of all heart diseases. It is a long-term illness, often associated with disability and characterized by life-threatening exacerbations, that results in multiple problems for patients and their families. This paper will provide a framework for nursing action designed to maximize the quality of life of chronic heart failure patients and their families. The approaches suggested by Strauss et al. (1984) and the principles of self-care as outlined by Levin, Katz and Holst (1979) provide the theoretical basis for the suggested nursing actions. A brief overview of the pathophysiology and current treatment of heart failure is also included. PMID- 1290582 TI - Recognizing panic in cardiac patients. AB - Patients presenting with apparent myocardial infarctions may in fact be suffering from panic attacks; many symptoms of the latter mimic those of the former. Cardiovascular nurses who know what to listen for in patients' descriptions can recognize indications that panic may be occurring. This article describes panic attacks, panic disorder, and the long-term consequences that often accrue when this highly treatable problem is not recognized. Particularly when no evidence of myocardial damage is found, a cardiovascular nurse's recognition of panic can lead to a referral for appropriate psychological treatment, preventing years of needless suffering and unnecessary health care costs. PMID- 1290584 TI - Vitamin C and plasma cholesterol. PMID- 1290583 TI - Is copper an antioxidant nutrient? PMID- 1290585 TI - On the use of the WLF model in polymers and foods. AB - The validity of the WLF model with fixed "universal" coefficients was tested against that of the model original form with variable coefficients using published coefficients of polymers and amorphous sugars crystallization and viscosity data. The disagreement between the two versions of the model is particularly large at temperature ranges starting about 20 to 30 degrees K above the glass transition or reference temperature, excluding the former from being a model of general applicability. Because the WLF model mathematical structure entails the existence of an almost linear region near the reference temperature, establishment of its validity as a kinetic model and meaningful determination of its constants requires data spread over an extended temperature range, especially when the experimental results have a scatter. PMID- 1290586 TI - Phenolic antioxidants. PMID- 1290587 TI - Changes of soluble glycoproteins in dystrophic (dy/dy) mouse muscle shown by lectin binding. AB - Lectin binding sites in skeletal muscle from normal and dystrophic (dy/dy) C57 BL/6J mice were demonstrated by use of histochemistry and electrophoresis combined with electron microscopy. The following lectins were used: Canavalia ensiformis Con A, Triticum vulgaris (WGA), Glycine max (SBA), Griffonia simplicifolia (GS II), Arachis hypogaea (PNA), Pisum sativum (PSA) and Lens culinaris (LCA). After incubation of frozen sections with Con A, WGA, GS II, PSA and LCA a sarcoplasmic staining was observed in both normal and dystrophic muscle. The most consistent light microscopic observations in the dystrophic muscles were a decreased staining intensity of the sarcoplasm after incubation with Con A, WGA, PSA and LCA, but not with GS II, and a strong staining of the interfiber connective tissue. Supernatants, deprived of organelles and membranes, were prepared from normal and dystrophic muscle by high speed centrifugation. Lectin stained Western blots of the supernatant from dystrophic muscle showed two bands (120 and 67 K) with high affinities to avidin. Further this supernatant contained two glycoprotein bands (180 and 140 K) with affinities to Con A and a number of glycoprotein bands with apparent molecular weights below 67 K showing affinities to LCA and PSA. None of these glycoprotein bands could be detected in the supernatant from normal muscle. These changes of the muscle carbohydrate components might be involved in the expression of the dystrophic syndrome This seems to be the first report on changes of soluble glycoproteins in muscular dystrophy. PMID- 1290588 TI - Anemia of inflammation: role of T lymphocyte activating factor. AB - Varied conditions associated with immune activation (rheumatic, infectious and malignant) are associated with a syndrome characterized by selective erythropoietic suppression. The pathogenesis of this anemia is unknown. We have cultured intact marrows from 11 patients and found decreased erythroid colony forming activity (CFU-E: colony forming unit-erythroid; p < 0.01). We analyzed sera from 23 patients with infectious, rheumatic and malignant disorders for their ability to render normal human T lymphocytes inhibitory to autologous CFU-E and burst forming unit-erythroid in vitro. Following exposure to serum from some anemic patients, normal T cells were observed to inhibit autologous CFU-E when compared to the effect elicited by T cells incubated with heterologous normal serum. Pooled data from 19 (7 not anemic, 12 anemic) serum samples using 8 different normal T cell and marrow donors revealed a significant correlation (r = 0.65, p < 0.01) between each patient's hemoglobin level and the ability of his/her serum to render T cells suppressive to CFU-E in vitro. The suppression mediated by patient serum exposed T cells on autologous CFU-E could be ameliorated by increased concentrations of erythropoietin. The serum factor was heat stable (56 degrees C) and could not be eliminated by neutralizing antibody to either gamma-interferon or tumor necrosis factor-alpha. We conclude that some patients with anemia of inflammation may have a circulating factor(s) which renders normal T lymphocytes suppressive to autologous CFU-E in vitro. The presence of a circulating serum factor in these patients may help explain how inflammatory events distant from the marrow mediate the erythropoietic suppression characteristic of this syndrome. PMID- 1290589 TI - Mechanism of accumulation of macrophages in galactosamine-induced liver injury: effect of lipoxygenase inhibitors on chemotaxis of spleen cells. AB - In an attempt to clarify a mechanism of macrophage infiltration in galactosamine induced hepatic injury, we investigated chemotactic factor(s) generated by murine hepatocytes exposed to galactosamine. Hepatocytes, isolated from murine liver by perfusion and digestion with collagenase, were incubated with galactosamine. Conditioned medium was collected 24 h later and chemotaxis of murine spleen cells was measured by stimulation of the conditioned medium using a modified Boyden chamber. Chemotactic activity was demonstrated in the conditioned medium of hepatocytes exposed to more than 3 mM galactosamine. Chemotactic activity of the conditioned medium was not reduced after freeze-thawing, and found to be dialyzable (molecular weight < 12,000). Trypsin (0.25%, 37 degrees C, 30 min) or heat (56 degrees C, 30 min) treatment reduced chemotactic activity of the conditioned medium. Furthermore, chemotaxis of spleen cells was decreased in the presence of lipoxygenase inhibitors (azelastine, ketotifen). These results suggest that accumulation of macrophages in the liver could be mediated by chemotactic factor produced by the galactosamine-treated hepatocytes, and that this mechanism may contribute to the pathogenesis of hepatic injury induced by galactosamine. PMID- 1290590 TI - Differences in the capacity of gamma-interferons from different species to induce class I and II major histocompatibility complex antigens on neonatal rat Schwann cells in vitro. AB - We compared the capacity of unfractionated cytokines and recombinant gamma interferons (gamma-IFN) to induce major histocompatibility (MHC) antigens on neonatal rat Schwann cells and endoneurial fibroblasts in vitro. Rat and mouse gamma-IFN were capable of induction of both class I and class II MHC antigens on both cell types although rat gamma-IFN was more potent than that of mouse. Human gamma-IFN failed to induce MHC class I or class II on either cell type. Unfractionated cytokines from the different species also differed in their capacity to induce MHC antigens. Differences in species of origin of cytokine mixtures as well as in individual cytokines, such as gamma-IFN need to be considered in studies of MHC induction. The presence of MHC class I and class II antigens on Schwann cells could render them susceptible to cytotoxic reactions and allow for the presentation of antigen, respectively. PMID- 1290591 TI - Inability of human immunodeficiency virus to infect human microvascular endothelial cells. PMID- 1290592 TI - Dentigerous cyst in a dog. AB - An infrequently occurring tumor-like lesion arising from the cellular components of the developing dental follicle is the dentigerous cyst. These odontogenic cysts have classic clinical and radiographic findings. The cysts are locally invasive and aggressive and require prompt surgical management. This case describes the diagnosis and surgical treatment of a dentigerous cyst in the mandible of a dog. PMID- 1290593 TI - Lingually displaced mandibular canine teeth: orthodontic treatment alternatives in the dog. AB - Lingual displacements of mandibular canine teeth often occur following retention of deciduous canine teeth. This condition often results in trauma of occlusion to the lingual aspect of the maxillary canine tooth and the further development of a periodontal pocket or an oronasal fistula. This condition can be corrected using orthodontic appliances. The purpose of this paper is to discuss and illustrate the various alternatives available for correction of this common malocclusion in dogs. PMID- 1290594 TI - Using epoxy for dental castings. AB - Important features of epoxy, when used for making dental castings, include rapid production of models without mixing and the production of a precise and nearly indestructible model. The 3M Epoxy system is used to illustrate the step-by-step production of an epoxy study model. PMID- 1290595 TI - Modified surgical treatment of intermittent open-mouth mandibular locking in a cat. AB - Intermittent open-mouth locking related to disorders of the temporomandibular joint are not uncommon. As a result of joint laxity, the mandible shifts to one side. The coronoid process then becomes locked lateral to the zygomatic arch. These patients present with the mouth opened and an inability to close the mouth. This article describes a case of intermittent open-mouth mandibular locking in a cat and a modified surgical treatment combining zygomatic arch and coronoid process reduction. PMID- 1290596 TI - Craniofacial development and growth in the dog. AB - Numerous types of veterinary orthodontic treatments are reported in papers and during meetings, however little is generally known concerning craniofacial growth in dogs. Most statements in veterinary dental publications are drawn from human oriented studies. This makes decision making in veterinary orthodontics difficult. The purpose of this paper is to review studies of craniofacial growth performed in dogs. PMID- 1290597 TI - Diagnostic approach to malocclusions in dogs. AB - Malocclusions may be associated with any of the cranial shapes recognized in dogs. Orthodontic treatments for malocclusions are frequently reported. However, these reports often lack a diagnostic plan and use confusing terminologies. The purpose of this paper is to describe, using standardized terms, a diagnostic approach to the most common malocclusions found in dogs. PMID- 1290598 TI - Classification and prognostic factors of endodontic-periodontic lesions in the dog. AB - The classification of the possible pathologic relationships between the periodontium and endodontium in man includes three separate groups. This classification system is adapted for utilization in the dog to clarify the appropriate treatment and prognosis of dog's teeth affected with endodontic periodontic lesions. This article describes the classification and treatment planning with illustrations of each type. PMID- 1290599 TI - The influence of dry food on the development of feline neck lesions. AB - The pH of the tooth surface was determined in cats with neck lesions. The presumption that commercial dry cat food with an acid coating can lead to neck lesions is investigated. In general cats with neck lesions had lower pH values of the tooth surface (7.93 +/- 0.61) than healthy cats (8.65 +/- 0.58). Feeding dry cat food with an acid surface did not contribute to the pathogenesis of neck lesions. PMID- 1290600 TI - The Angle classification system of malocclusion: is it appropriate for use in veterinary dentistry? AB - Classifications of malocclusions in dogs have superficially followed the Angle's system. Since teeth anatomy and occlusal relationships are not the same for dogs as for humans, the use of the Angle's system can be misinterpreted. The proposal for a system for classification of malocclusions specific to the dog is presented with a discussion of the Angle's classification of malocclusions. PMID- 1290601 TI - Natural development of periodontal disease in the dog: a review of clinical, anatomical and histological features. AB - Periodontal disease occurs naturally in a wide range of species from rodents to humans. Clinical studies document the development of periodontal disease. Histopathology reveals the inflammatory response to plaque accumulation. This article presents a review of the clinical and histopathological features of periodontal disease in the dog. PMID- 1290602 TI - Root canal obturation using Thermafil endodontic obturators in dog teeth. AB - The technique of using Thermafil endodontic obturators to fill root canals in dog teeth is discussed in detail. Stainless steel carriers coated with gutta-percha were heated and inserted in instrumented canals of dog teeth. The ease of the technique is discussed and obturation efficacy is evaluated. No perfect apical seal was achieved. PMID- 1290603 TI - Dens in dente in a six year old doberman pinscher. AB - Developmental abnormalities of tooth shape and form are rare. Identification of dens in dente is made by radiographic and clinical examination. Pulpitis, pulp necrosis and periapical inflammation can be associated with this abnormality. The tooth should be evaluated for endodontic therapy. A review of the literature related to dens in dente is described with the findings in a doberman pinscher. PMID- 1290604 TI - Microleakage of a composite inlay system. AB - This study investigated the marginal seal of resin composite inlays in dentin and enamel when either unfilled resin or a second or third generation dentin bonding agent is used. Standardized mesial and distal inlay cavities were cut in 135 human third molar teeth. The teeth were randomly divided into 9 groups and inlays fabricated in a hybrid resin composite inlay material. Each group of teeth was then treated with one of 8 dentin bonding agents or an unfilled resin and cemented with a dual curing resin cement. Each group was stored in deionized water for 1 week, thermocycled between 5 degrees C, 37 degrees C and 55 degrees C for 500 cycles, then placed in 2% methylene blue solution for 15 hours. Following this the teeth were sectioned and scored for the degree of leakage observed. Marginal microleakage was minimal at enamel margins, however there was marked leakage, even when a dentin bonding agent was used, on the dentin side. Only two dentin bonding agents proved more effective than unfilled resin and in only one case was the leakage not significantly worse than in enamel. PMID- 1290605 TI - A laboratory study of the Amalgambond Adhesive System. AB - The shear bond strengths (SBS) of the Amalgambond Adhesive System to several substrates were determined in vitro. Ninety extracted human permanent first and second molars were used. In 30 teeth, the occlusal surfaces were ground wet on 600-grit SiC to expose the enamel and in 60 to expose the superficial dentin. Amalgam (Tytin) restorations were placed on 15 exposed dentin surfaces and sandblasted. The Metafil-A composite was transferred in three increments and each cured for 30 seconds. The SBS of the composite to enamel were determined 1 minute (A) and 24 hours after final cure (B); to dentin 1 minute (C) and 24 hours after final cure (D); of freshly mixed amalgam to dentin (E) and to previously placed amalgam (F) after 24 hours. All of the 24 hours specimens were stored in saline at 37 degrees C or 24 hours. A shear load was applied to the base of the bonded cylinders with a knife-edged rod in an Instron machine at a crosshead speed of 0.5 mm/min. The SBS were expressed in MPa and the data analyzed by Student t test, ANOVA and Student-Newman-Keuls test. The mean +/- SD of SBS were: A: 8.15 +/- 1.74; B: 15.69 +/- 4.50; C: 6.64 +/- 1.72; D: 17.09 +/- 4.61; E: 5.10 +/- 1.73; F: 6.54 +/- 3.78. The SBS to enamel and to dentin, respectively, after 24 hours were significantly greater than after 1 minute (P = 0.0001), the SBS of A vs C (P = 0.1783), B vs D (P = 0.2180) and E vs F (P = 0.7149) were not significantly different. PMID- 1290606 TI - Tensile adhesion evaluation in a new universal test. AB - A tensile testing jig was designed to test adhesion between various materials and tooth surfaces, and between materials of various consistencies, modes of setting and properties. This study examined the adhesion of both flowable and condensable, light cured and chemically cured, direct and indirect restorative materials to dentin. All materials were mixed and placed according to manufacturer's directions. The bonds were tested in tension after 24 hours. The substrate was dentin, except in group 1. Results in MPa +/- SD: 1. Photobond & Photoposterior to enamel 15.84 +/- 3.93; 2. Superbond C&B and metal inlay 6.20 +/ 3.00; 3. SuperBond C&B and amalgam 5.76 +/- 1.89; 4. All-Bond and metal inlay 4.46 +/- 1.16; 5. Mirage Bond and Newbond and amalgam 2.97 +/- 0.85; 6. Vitrebond 2.06 +/- 0.95; 7. Newbond and amalgam 1.70 +/- 0.61; 8. Ketac-Bond 0.73 +/- 0.40. The groups (2,3,4), (4,5), (5,6,7) and (6,7,8) were not significantly different at the 95% confidence level, calculated by the Student-Newman-Keuls test. The testing method was useful for all materials studied. PMID- 1290607 TI - Accuracy of second pour casts using dual-arch impressions. AB - This study compared the accuracy of the second pour of addition silicone impressions made using custom acrylic resin complete-arch trays and two types of dual-arch trays. Thirty impressions were made of a typodont using metal dual arch, plastic dual-arch and acrylic resin complete-arch custom trays (10 impressions/group). Tooth #30 (first molar) and tooth #32 (third molar) in the typodont were custom metal dies made in the shape of complete crown preparations. On the metal dies were scribed reference marks permitting measurements to be made in the mesial-distal, buccal-lingual and occlusal-gingival dimensions. In addition, an inter-tooth measurement between tooth #30 and #32 was made. Following impression procedures, gypsum casts were poured. The casts were removed from the impression and, 24-hours later, second pours were completed. The distances between reference marks on each cast were measured using a measuring microscope. The measurements from each second pour cast were used to compute a group mean, with values expressed as a percent deviation from the master model. A two way analysis of variance was used to compare the groups. No statistically significant differences were found in accuracy among the three type trays except in the inter-tooth measurement where the metal dual-arch tray was more accurate than the other trays. PMID- 1290608 TI - Microleakage in the sandwich technique. AB - This study assessed the microleakage and if it was possible to reproduce the success that is seen in the oral cavity with properly placed "sandwich" restorations. Simulated Class V erosion lesions were prepared in extracted human molar teeth and restored using a Type III glass ionomer lining cement mixed mechanically at a high powder:liquid ratio of 3:1 or greater with resin composite laminated to it leaving cement exposed at the gingival margin. To update the technique for modern materials a dual cure glass ionomer lining cement was placed in a second series with resin composite laminated to it completely covering the gingival margin. The restorations were stored in water for two weeks before temperature cycled and immersed in dye. The results showed minimal leakage relative to most other published studies and that most leakage was related to the setting shrinkage of the resin composite. PMID- 1290609 TI - Effect of fluoride concentrations on overdenture abutments. AB - This study evaluated the preventive effect of four concentrations of fluoride. Twenty-five extracted caries-free anterior teeth from patients aged 50-70 were prepared as overdenture abutments. The teeth were sectioned mesiodistally into two halves. The teeth were covered with a protective varnish, leaving a window on the root surface and one on the cut dentin of the occlusal. The root halves were randomly divided into 5 groups of 10 specimens and each group received a different 5-minute topical treatment prior to being placed in the demineralizing solution. The treatments were: Group 1: distilled H2O only; Group 2: 100 ppm F-, Group 3: 250 ppm F-, Group 4: 500 ppm F-; and Group 5: 1000 ppm F-. The teeth were cycled for 6 hours in a demineralizing solution and for 17 hours in a fluoride-free remineralizing solution. The cycling was maintained for 10 days. The root halves were sectioned and prepared for histologic examination. The depth of the lesions were measured from standardized photo-micrographs by means of a sonic digitizer. The conclusions were: (1) the lesions on the root surface were too small to be measurable, (2) the lesions on dentin were all of similar depth, and (3) the lesions had bands within them and the width of these bands showed a dose response to the fluoride concentration of the topical application. PMID- 1290610 TI - Methodology for proximal wear evaluation in posterior resin composites. AB - The purpose of this study was to utilize a methodology to measure proximal wear of posterior resin composites with respect to time. A group of 10 teeth (5 premolars and 5 molars) were restored with P-30, a posterior resin composite restorative. At placement the proximal contacts were judged to be closed visually, and with unwaxed dental floss. The patients were then recalled at intervals of 6, 12, and 36 months for indirect wear evaluations. Resin composite transfer copings were made and indexed on baseline models. A zoom stereomicroscope, at 20 microns resolution, was used to determine proximal wear. For the posterior restorative material the premolar and molar teeth wore at the same rate. The amount of wear was statistically greater for premolar teeth at 6 and 12-month evaluation periods than molar teeth. At 36 months, there was no statistical difference in wear between premolar and molar teeth. PMID- 1290611 TI - Clinical evaluation of light-cured anterior resin composites over periods of up to 4 years. AB - Seven hundred light-cured anterior restorations were placed in the permanent teeth of 161 patients by one researcher and evaluated over 4 years. One microfilled and two hybrid resins were assessed for their handling and for gingivitis adjacent to them, surface staining, marginal staining, and color mismatch. Restorative failures were related to the material, patient age, tooth site, and class of preparation. The different handling properties of the three resins did not affect their clinical behavior. There were only 10 unsatisfactory instances from 1626 restoration observations for the four clinical parameters assessed, and no clinically significant differences were found between the three materials, apart from the initial lighter shade mismatches of the microfilled resin. There was no obvious clinical deterioration recorded for most of the restoration observations, although all restorations deteriorated slightly over the study. There were no significant failure differences between the three resins, but significantly more failures occurred in elderly patients, restored (Class V) premolar teeth, and Class IV and V preparations. Of the 43 restoration failures, 81% were from Class V preparations, which reflected undue reliance on a dentin-bonding resin system for restoration retention in premolar cervical abrasion-erosion lesions. PMID- 1290612 TI - Effect of resin primer solvents and surface wetness on resin composite bond strength to dentin. AB - This study investigated the effect of various solvents on resin composite bond strength to dentin with both wet and dry dentin. A generic dentin bonding system was created with HEMA as the resin in the primer. The highest bond strengths were obtained when acetone was used as the solvent on a wet dentin surface; the lowest bond strengths were obtained with water as the solvent and the primer placed on a wet dentin surface. PMID- 1290613 TI - Enamel shear bond strengths after vital bleaching. AB - This study examined the shear bond strengths of enamel bond formed at specific time intervals after the termination of vital bleaching. A total of 160 extracted human anterior teeth were divided into three bleaching treatment (BTx) groups (Superoxol, Proxigel, White & Brite), two bonding agent (BA) subgroups (Scotchbond Dual Cure, Scotchbond 2) and two BA control groups. After BTx for 30 days, bonds were formed at 1, 6 and 24 hours; 3 and 7 days (time interval, TI) post-termination of BTx. A total of 32 groups of n = 5 were used. Bonds were formed in nylon tubes with selected BA and Silux Plus, and ruptured 24 hours later with Instron and cable/loop to measure enamel shear bond strength (SBS). A 3 x 2 x 5 factorial ANOVA and Tukey 95% confidence interval (TCI) detected significant differences between BTx (F = 3.54; TCI = 2.7 MPa), BA (F = 9.73; TCI = 1.8 MPa) and TI (F = 9.39; TCI = 4.1 MPa). The interaction between BTx and TI was slightly significant (F = 2.02); other interactions were not significant. Post-hoc analysis showed 80% of bonds failed at the interface or by mixed cohesive composite/interfacial failure. Scanning electron microscope observations suggested association of increased density of voids in bond area at TI with lowest mean bond strengths. SBS ranged from 42.3 to 106.8% of control. PMID- 1290614 TI - Dimensional accuracy and bond strength of addition silicones. AB - A cross-matching study was conducted to evaluate the effect on dimensional accuracy and tensile bond strength between the materials when intermixing brands of addition silicone impression materials in a putty-wash impression. Three brands of putty-wash systems (Reprosil, Permagum, and Express), which formed nine possible combinations, were involved in this study. The dimensional accuracy was estimated from stone casts recovered from impressions of a standardized stainless steel master model. Findings indicated no adverse effect on the bond between putty and light-bodied materials of different brands. Statistical analysis indicated significant differences. However, because the actual differences in percent deviations between the intermixed groups and their respective reference groups are very small, they are presumed to be insignificant clinically. PMID- 1290615 TI - Enamel, cementum and dentin fluoride uptake from a fluoride releasing resin composite. AB - The purpose of this study was to determine the fluoride release by and the enamel, cementum and dentin fluoride uptake from a visible light-cured fluoride containing resin composite. Seven circular discs of the composite were prepared and the fluoride release in distilled water determined at daily intervals for 14 days, and then after 30, 90, 180, 365 and 550 days. The baseline fluoride concentrations in enamel and cementum were determined in three successive depths by an acid etch biopsy procedure and in dentin by an abrasion biopsy procedure. Composite slabs were prepared and ligated to the enamel, cementum and dentin surfaces and the teeth were suspended in synthetic saliva for 7 or 30 days. After removal of the composite, similar biopsy procedures were performed. The teeth were then immersed in 1 M KOH for 24 hours and similar biopsies done. The fluoride concentrations were adjusted to standardized depths of 2.0 microns for enamel, 4.0 microns for cementum and 10.0 microns for dentin, and the total and bound fluoride uptake calculated. The fluoride release from the composite dropped sharply after 1 day and after 180 days reached a plateau which remained relatively constant up to 550 days. The results of this in vitro study indicated that the mineralized dental tissues acquired fluoride at various depths. PMID- 1290616 TI - Rationale for the chemical development of angiotensin II receptor antagonists. AB - The renin-angiotensin system (RAS) has been demonstrated to be a key element in blood pressure regulation and fluid volume homeostasis. Since angiotensin II (AII) is the effector molecule of the RAS, the most direct approach to block this system is to antagonize AII at the level of its receptor. Therefore, at Du Pont Merck the working hypothesis has been that the identification of metabolically stable and orally effective AII-receptor antagonists would constitute a new and superior class of agents useful in treating hypertension and congestive heart failure. Our program began with a detailed pharmacologic evaluation of some simple N-benzylimidazoles, originally described by Takeda Chemical Industries in Osaka, Japan. They were found to be a series of weak but selective AII-receptor antagonists with a competitive mode of action. We embarked on a program aimed to design and synthesize more potent and orally effective nonpeptide antagonists, while attempting to preserve their selective affinity for the AII receptor. The first major breakthrough in our efforts to increase the potency of these compounds came with the development of a series of N-benzylimidazole phthalamic acid derivatives. Although effective at lowering blood pressure when administered intravenously, the phthalamic acids were devoid of oral activity. The first orally active AII antagonists came with the discovery of the biphenyl carboxylic acids. Although these compounds are absorbed after oral dosing, their bioavailability was less than desired. In the hope of improving the oral absorption of these biphenyls, we investigated a variety of acidic groups as bioisosteric replacements for the carboxylic acid. The key to the discovery of nonpeptide AII-receptor antagonists with improved oral activity and duration of action resulted from replacing the carboxylic acid group with the isosteric but more lipophilic tetrazole ring. Hence, our efforts culminated in the discovery of losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4 yl)methyl]imidazole, potassium salt), a highly potent angiotensin type 1 (AT1) selective receptor antagonist with a long duration of action. Losartan is currently undergoing clinical investigation for the treatment of hypertension. The history, including the rationale for the design of the compounds, and ensuing structure-activity relationships of losartan and related analogs will be described. Many of the newer compounds exceed the potency of losartan, and the best compounds in the series rival the affinity of the endogenous ligand, AII, for its receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1290617 TI - Angiotensin II receptors and functional correlates. AB - Angiotensin II (ANG II) is the primary mediator of the renin-angiotensin system, which has an important functional role in cardiovascular homeostasis. The angiotensin receptor and its functional correlates have been redefined by the cloning of angiotensin receptors and the discovery and widespread study of specific nonpeptide ANG II-receptor antagonists losartan (AT1 selective) and PD123177 (AT2 selective). With these antagonists, it has been possible to extend the concept of ANG II-receptor heterogeneity to virtually every tissue and species. The losartan-sensitive sites have been shown to mediate all of the major ANG II-induced biologic effects, including vasoconstriction, aldosterone and catecholamine release, and central, ANG II-induced drinking behavior. The function of the AT2 site is not fully understood, but it may be involved in neuronal ion channel modulation and in fibroblast collagen metabolism. The presence of AT2 sites in fetal tissues and in discrete locations in the brain has encouraged continued research. Losartan, which represents the first of a new class of therapeutic agents, is currently undergoing clinical trials. A growing number of other AT1-selective ANG II-receptor antagonists are under development, including L-158,809, SKF 108566, and GR117285. Rat AT1-receptor subtypes have been cloned and sequenced (AT1A and AT1B). Human ANG II receptors have also been cloned and shown to have high affinity for losartan. A number of atypical angiotensin-binding sites have been identified from mycoplasma, amphibians, and mouse neuroblastoma, which are not sensitive to either losartan or PD123177.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290618 TI - Molecular cloning of AT1 angiotensin receptors. AB - Angiotensin II is the principal effector molecule of the renin-angiotensin system. Its effects are mediated by cell surface proteins termed AT receptors. On the basis of radioligand binding studies, these have been pharmacologically subdivided into two classes, termed AT1 receptors and AT2 binding sites (Chiu AT, et al, Biochem Biophys Res Commun 1989;165:196-203). AT1 receptors appear to mediate the major cardiovascular effects of angiotensin II, whereas no known physiological properties appear to be coupled to AT2 binding sites (Wong PC, et al, J Pharmacol Exp Ther 1990;255:584-592). To gain further insight into the function of AT1 receptors we have isolated rat cDNA's and genes encoding two distinct but highly similar isoforms of AT1 receptors, termed AT1a and AT1b receptors. Two cDNA's encoding the vascular AT1a receptor were isolated by an expression cloning strategy from a cDNA library prepared from vascular smooth muscle cells. The properties of the clones isolated by this approach are consistent with known pharmacological, biochemical signaling, and tissue distribution properties of AT1 receptors. Using this cDNA as a probe, a second isoform of rat AT1 receptor was isolated from a genomic library. This receptor, termed the AT1b receptor, is 95% identical in amino acid sequence and is pharmacologically indistinguishable from the AT1a receptor. However, the tissue specific expression pattern of the AT1b gene differs significantly from that for the AT1a receptor. PMID- 1290619 TI - Clinical experience with angiotensin II receptor antagonists. AB - This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case. PMID- 1290620 TI - Clinical experience with the angiotensin II receptor antagonist losartan. A preliminary report. AB - The nonpeptide angiotensin II (AII)-receptor antagonist losartan is a selective blocker of the pressor effects of AII. It is now being evaluated as an anti hypertensive drug in multicenter clinical trials in the United States and other countries. Preliminary inpatient studies have shown that after 5 days of treatment, losartan--in doses of 50, 100, and 150 mg--is significantly more effective than placebo in decreasing blood pressure, and has efficacy similar to that of the angiotensin-converting enzyme (ACE) inhibitor enalapril. Large-scale dose-ranging studies in ambulatory hypertensive patients have shown that 10- and 25-mg losartan doses have brief effects in lowering blood pressure, but when given once daily, 50 mg is the minimal dose needed to produce significant day long decreases in blood pressure. Interestingly, higher doses do not appear to exhibit greater efficacy; however, the effects of these doses are all similar to those of enalapril (20 mg once daily). Losartan's long duration of action is documented by ratios of trough (end of 24-h dosing interval) to peak antihypertensive effects, which are consistently above 50%. Clinical experiences thus far have indicated a low incidence of adverse events. Preliminary animal and in vitro investigations have shown that losartan produces beneficial effects on cardiac function, renal function, and survival that are similar to those of ACE inhibitors. Additional studies are now under way to define more fully the cardiovascular and metabolic profiles of losartan. PMID- 1290621 TI - Improving hypertension treatment. Where should we put our efforts: new drugs, new concepts, or new management? AB - Despite the availability of numerous antihypertensive agents, a concerted research effort to develop new approaches to hypertension treatment is necessary. Published results of large multicenter trials emphasize the benefits of available treatments in highly selected patients. A critical look at the results shows that treatment failure is frequent and side effects are common. In the Systolic Hypertension in the Elderly Program, 28 to 35% of patients did not reach the goal blood pressure, 13% stopped treatment because of side effects, and 21% required medication other than a diuretic and a beta-blocker. Basic research may bring forth novel concepts of treatment, such as neutral endopeptidase inhibition, renin inhibition, or new techniques such as gene therapy. In the meantime, among many other lines of research, type 1 angiotensin II-receptor antagonists represent a promising new group of agents for the vast majority of hypertensive patients who are renin-dependent. A different global approach to hypertension management is also needed. Because hypertension is a heterogeneous disease, individual sequential monotherapy or the "N of 1" trial aim to select the most effective drug for each patient. To achieve the accurate assessment of drug efficacy that is a prerequisite for this approach, the number of blood pressure measurements before and during drug administration must be increased. For this purpose, self-blood pressure measurement and teletransmission of results to the physician will provide a major treatment advance. PMID- 1290622 TI - Uses of biological markers. PMID- 1290623 TI - Biological markers and truth-telling. PMID- 1290624 TI - Nonneural markers in Alzheimer disease. AB - Nonneural tissues are now widely used to search for abnormalities in genes as well as for other markers of dementia of the Alzheimer type (DAT). Studies of nonneural tissues can experimentally circumvent problems inherent in the study of autopsy brain, but to be meaningful, abnormalities identified in the periphery must be correlated with abnormalities in the brain, which is the tissue of clinical interest. Among the topics in DAT research that can be readily studied in nonneural cells (including tissue cultures) are molecular genetics, amyloid precursor protein formation and metabolism, systemic manifestations of immunological and inflammatory mechanisms, proteolysis, membranes, signal transduction, and mitochondria and metabolism. Although phenomena suggesting the possibility of cytoskeletal abnormalities in nonneural DAT cells have been described, the tau molecules involved in paired helical filament formation are relatively brain-specific. Since the neuropathological diagnosis of DAT depends on recognizing a pattern of changes rather than any single abnormality, it seems unlikely that any one laboratory abnormality in peripheral tissues will correlate precisely with the clinicopathological entity of DAT. However, abnormalities found in nonneural DAT cells that correlate with the existence of similar abnormalities in the brain are likely to be informative about the disease process in the patients in whom they occur. PMID- 1290626 TI - Science, shmience. Is your handpiece safe? Welcome to the information age. PMID- 1290625 TI - An examination of psychometric properties of the extended scale for dementia in three different populations. AB - The Extended Scale for Dementia (ESD), a development of the Mattis Dementia Rating Scale, has been used in the evaluation of dementia and aging and has shown substantial clinical utility. We report on analyses of its properties and internal structure in three samples of older people: 153 normals, 101 psychiatric hospital residents, and 114 patients with Alzheimer disease. The results showed good internal consistency in the two clinical samples, with much lower reliability in the normals, for whom the test was too easy. A review of the item statistics led to the use of 17 of the 23 ESD items in item component analyses in the three samples. Use of Horn's parallel analysis criterion led to the retention of three components in the normal group and one in both the hospital and Alzheimer groups. The results are compared with other work and are in accordance with the view that cognitive structure becomes more simple with increasing dementia. PMID- 1290627 TI - A humanitarian trek to Bolivia. PMID- 1290628 TI - WDA pushes for UCR ruling. PMID- 1290629 TI - Wash away the UCR blues. PMID- 1290630 TI - Present status of boron neutron capture therapy. AB - The neutron capture reaction 10B(1n,4He)7Li produces two energetic particles, 4He2+ and 7Li3+ that are strongly cell toxic. Due to the short range of these nuclear fragments (5-9 microns) mainly those cells that have bound or internalized a 10B-containing substance are growth-inactivated. The most critical and difficult step in an efficient boron neutron capture therapy (BNCT) is the tumour targeting. It is today possible to synthesize a large number of boron compounds and conjugate them to tumour-seeking macromolecules, such as monoclonal antibodies or different polypeptides. The boron-containing substances presently considered for therapy are sulfhydryl boron hydride (BSH) and boron phenylalanine, (BPA) for the treatment of gliomas and malignant melanomas respectively. Other boronated compounds considered are ligands for receptor amplified tumour cells, antibodies for tumour cells with specific antigens and thioureas for treatment of melanotic melanomas. The required boron concentration is given by the relative dose due to neutron capture in 10B and that of the competing capture reactions in nitrogen and hydrogen. Capture in nitrogen produces protons with a range of about 10-11 microns and this gives a radiation dose to all cells in the neutron activated area. Calculations show that the local concentration of 10B near the critical radiation target, DNA, must be higher than 10 ppm (10 micrograms/g). Increased emphasis will be put on the development of combinations of treatments that fulfil the requirements for attacking the microscopic spread of the tumour. PMID- 1290631 TI - Repeated screening for carcinoma of the prostate by digital rectal examination in a randomly selected population. AB - Of 9,026 males aged 50-69 years, 1,494 were randomly selected and invited to participate in a programme including two screenings for carcinoma of the prostate by digital rectal examination performed in 1987 and 1990. The remaining 7,532 served as a control group. Of the selected persons, 78% accepted the invitation to the first screening round and 70% to the second one. Carcinoma of the prostate was suspected in 45 of 1,163 men examined at the first screening round and in 42 of 953 at the second round. Carcinoma was confirmed by fine-needle aspiration biopsy in 13 cases from the first and in 7 from the second round. In the study group, 17.4 carcinomas were diagnosed per 1,000 men and in the control group 8.6 per 1,000 men. The screening cost was 1,640 pounds per detected cancer and 2,343 pounds per detected and potentially cured cancer. Screening for carcinoma of the prostate by digital rectal examination can be organised with a high population acceptance, and at a reasonable cost. The impact of screening on mortality in prostatic cancer remains uncertain. PMID- 1290632 TI - Ceruloplasmin level in women with breast disease. Preliminary results. AB - The average ceruloplasmin levels of 29 patients with active breast cancer and 22 patients in remission were 824 +/- 61 mg/l and 630 +/- 18 mg/l respectively. The average ceruloplasmin level of 17 patients with benign breast diseases was 555 +/ 29 mg/l and of 18 healthy women in a control group 584 +/- 17 mg/l. Breast cancer patients not in remission had ceruloplasmin levels which were significantly increased when compared to the other 3 groups. The CA 15-3 levels and ceruloplasmin levels were positively correlated. We propose that ceruloplasmin may be used as a tumour marker in the follow-up of patients with breast cancer. PMID- 1290633 TI - Chordoma-natural history, treatment and prognosis. The Florence Radiotherapy Department experience (1956-1990) and a critical review of the literature. AB - Fifteen cases of chordoma, seen between 1956 and 1990 at the Florence Radiotherapy Department are reported. Twelve of them were treated with radiotherapy and surgery, while one was left untreated. We analyzed the course of the disease in the treated cases, with particular emphasis on the problem of symptom control. The natural history of the disease seemed to be only marginally affected by the treatment and new therapeutic options are strongly needed. While actuarial survival rates at 5 and 10 years were 58% and 35% respectively (owing to the slow growth rate of this neoplasm), 10 years' symptomatic progression free, symptom-free, and disease-free survival rates were only 25%, 17% and 8% respectively. PMID- 1290634 TI - Disodium pamidronate versus mithramycin in the management of tumour-associated hypercalcemia. AB - Twenty-eight consecutive hypercalcemic patients with cancer referred to our department were included in a randomized study, comparing the second generation bisphosphonate pamidronate (APD) with our standard treatment consisting of rehydration, mithramycin (repeatedly) and supportive care. Three patients were excluded, due to rapid deterioration and death, leaving 25 evaluable patients. APD was administered as a single i.v. infusion of 30, 60 or 90 mg depending on the serum calcium, while mithramycin was given in doses of 1.25 mg and repeated if necessary within the first three days. The primary endpoint of the study was the serum calcium day 6. APD normalized serum calcium in all patients, and 12 out of 14 were still normocalcemic day 12. In contrast, mithramycin was effective only in 3 out of 11 patients, and in these patients hypercalcemia recurred rapidly. The success of APD was underscored by the fact that the patients in this group achieved a significantly better performance status after treatment. No serious side-effects were recorded in either group. PMID- 1290635 TI - Metastases in the small intestine from a subcutaneous lower limb leiomyosarcoma. PMID- 1290636 TI - Modern imaging methods in oncology. AB - Modern imaging methods are very important in the management of patients with cancer and of their disease. It is vital that clinicians treating them understand the relevance of different imaging techniques for specific applications, so that the best choice can be made to aid diagnosis and monitor response to treatment. This review briefly covers the development and principles of the diverse imaging methods available, from the discovery of x-rays by Rontgen in 1895 to the recent techniques of magnetic resonance and positron emission tomography. The authors endeavour to point out the strengths and weaknesses of each method, using clinical examples where appropriate. Finally, future developments are discussed. It is hoped that this review will aid clinicians diagnosing and treating cancer patients to choose the most suitable imaging method for their patients from among the vast array available. PMID- 1290637 TI - Epidemiology on malignant melanoma in Europe. AB - Mortality and incidence of malignant melanoma of the skin is increasing at a rate of between 3 and 7% per year in many European countries. All over Europe melanoma is the cancer showing the most rapid increase in incidence. Within Europe the variation in incidence and mortality rates is close to a factor of ten with the disease being more common in northern than in southern Europe. Higher rates are consistently reported on intermittently exposed body sites. Skin melanoma differ from non-melanoma skin cancer with regard to sex-, age-, and anatomic distribution. There is mounting evidence from analytical studies that the increase in melanoma incidence is a result of intermittent recreational sun exposure. Severe sunburns, in particular, is a strong risk factor, being especially harmful in childhood. Outdoor work with chronic sun exposure is not associated with increased melanoma risk and it may even be protective. The total number of pigmented naevi is an important risk factor in several studies. Freckling, fair complexion, and skin which burns rather than tans at sun exposure, are other well-established risk factors. Today no non-solar environmental risk factors have been identified. Information campaigns based on our knowledge of risk factors, warning against excessive sun exposure should significantly reduce the incidence in the future. Population-based education of risk groups may lead to earlier diagnosis and thereby reduced mortality. PMID- 1290638 TI - Catheter mapping for localizing the origin of late post-infarct ventricular tachycardia. Value and limitations. PMID- 1290639 TI - Functional significance of premature ventricular complex morphology evaluated during treadmill exercise stress test in patients with coronary artery disease. AB - OBJECTIVES: To evaluate the relation between premature ventricular complexes morphology and left ventricular myocardial systolic function in patients with proved coronary artery disease. SETTING: Department of Cardiology at General Hospital. METHODS: From 112 patients (pts) with proved coronary artery disease, thirty-three pts with premature ventricular complexes (PVC) detected during treadmill exercise stress test were selected. Two groups of pts were considered: group I-20 pts with regular contour or with a narrow notching (< 40 ms; type I PVC) and group II-13 patients with wide notching (> 40 ms; type II PVC). In each group the following parameters were studied: ejection fraction, QRS duration, duration of exercise, number of metabolic units and the prevalence of ventricular aneurysm and mitral regurgitation. RESULTS: Statistical significant differences were found between group I and II concerning the mean ejection fraction (59.2% vs 48.6%; p < 0.05). The prevalence of ventricular aneurysm and mitral regurgitation was higher in patients with type II ventricular premature complexes (10% vs 30%). CONCLUSION: Particular characteristics of premature ventricular complexes detected during treadmill exercise stress test, in patients with proved coronary artery disease, suggest the presence of left ventricular myocardial systolic dysfunction. PMID- 1290641 TI - [Occurrence of dynamic atrial spontaneous contrast in patients with mitral disease]. AB - OBJECTIVE: The aim of this study was to analyze, through transesophageal echocardiography, different factors related to left atrial spontaneous echocardiographic formation. DESIGN: Transthoracic and transesophageal comparative study of left atrial thrombotic phenomena. SETTING: Ambulatory and in hospital patients referred to Gregorio Maranon General Hospital Echocardiographic Laboratory. PATIENTS: 120 consecutive patients with mitral valve disease or prosthesis were included in this transesophageal echocardiographic prospective study. All patients were divided in two groups, according with left atrial spontaneous contrast. In each patient we measured total left atrial area, rhythm abnormalities, mitral valve area, left atrial cavity thrombus and maximal mitral regurgitation area. MEASUREMENTS AND RESULTS: Transthoracic echocardiography did not detect any patient with left atrial spontaneous contrast, compared to 57.5% diagnosed through the transesophageal technique. Transesophageal echocardiography diagnosed left atrial thrombosis in 19% (n = 23) of patients compared to 1% (n = 2) through the transthoracic technique. In the group with left atrial contrast, 59% of patients had mitral regurgitation less than 600 mm2, 64% were in atrial fibrillation and left atrial total area was 28 +/- 10.8 mm2. CONCLUSIONS: Transesophageal echocardiography is the technique of choice to diagnose, with greater security, left atrial cavity thrombosis, and establish the relationship of echocardiographic variables and left atrial thrombotic phenomena. Among these echocardiographic factors, left atrial dynamic spontaneous echocontrast is fundamental. PMID- 1290640 TI - [Pulse wave velocity as expression of arterial compliance and its importance in the evaluation of arterial hypertension]. AB - STUDY OBJECTIVE: To determine the arterial compliance through the evaluation of pulse wave velocity. DESIGN: Open study with direct comparison of different groups within a 12 week evaluation period. PATIENTS: 69 patients, 49 with hypertension and 20 normals individuals. INTERVENTIONS: Different groups with the following treatments: Isradipine, Lisinopril, Dilevalol and no therapy. MEASUREMENTS AND MAIN RESULTS: There is marked differences in the pulse wave velocity when hypertensive patients are compared with normal individuals (p < 0.001). In a 12 week therapeutic evaluation there is an improvement in the pulse wave velocity particularly when the arterial pressure was lowered to normal values in the hypertensive patients: Lisinopril (p < 0.005), Isradipine (p < 0.005), Dilevalol (p < 0.025). CONCLUSIONS: It is very easy to evaluate the pulse wave velocity. Arterial compliance, which may be evaluated using the pulse wave velocity, is significantly reduced in hypertensive patients, compared with age matched control subjects. The use of antihypertensive drugs is associated with changes in arterial compliance. There is a significant decrease in the pulse wave velocity after the administration of ACE inhibitors, calcium channel blockers and beta blockers for an equivalent fall in blood pressure. These observations emphasizes the potential importance of the changes in the large arteries, considered as either an associated factor or a consequence of elevated blood pressure, in the evaluation of the cardiovascular morbidity, and mortality of patients treated for hypertension. PMID- 1290643 TI - [Amiodarone in heart insufficiency]. AB - The purpose of this study was to analyse the effects of amiodarone on the treatment of cardiac failure. The effects of 200 mg/day of amiodarone were assessed in 18 patients with a history of cardiac failure. Functional class, heart rate, blood pressure, left ventricular ejection fraction, heart size, treadmill exercise tolerance and electrocardiogram were assessed before and eight weeks after the use of amiodarone, and the side effects were monitored. In 18 patients receiving amiodarone, the functional class and heart rate decreased significantly (p < 0.05) from 2.7 +/- 0.4 to 1.2 +/- 0.4 and 103 +/- 15 to 69 +/- 8.5 beats/min respectively. The ejection fraction and the exercise tolerance increased significantly (p < 0.05) from 29.2 +/- 5.5% to 41.5% and from 379.8 +/- 271 sec to 897.8 +/- 350.8 sec respectively. The incidence of atrial and ventricular arrhythmias decreased significantly and no side effects were observed. Amiodarone appears to produce benefits in patients with cardiac failure with atrial and ventricular arrhythmias. PMID- 1290642 TI - [Formation of left ventricular thrombus in acute myocardial infarction: significance of the determination of fibrinogen, of products of fibrinogen degradation, and of plasminogen]. AB - OBJECTIVE: To evaluate the significance of the fibrinogen, the plasminogen and the fibrinogen degradation products levels as marks of left intraventricular thrombosis (LIVT) in acute myocardial infarction (AMI). METHODS: 219 consecutive patients of AMI admitted in a Coronary Care Unit of an University Hospital, were prospectively studied. All protocols included a clinical evaluation, an M-mode and 2D echocardiographic study and blood samples, at day 1, 3, 7 and at hospital discharge. In the intraventricular thrombus evaluation just the 4 Asinger grade was considered. In the laboratory evaluation we used: the Clauss chronometric method for the fibrinogen, the colorimetric method for the plasminogen and the agglutination in plaque for the FDP. The patients with ECO in the 2 or 3 Asinger grades and those in which ECO and laboratory study were not performed in the same day, were excluded. 101 patients remained on the study, and they were divided in two groups: 53 patients with LIVT and 48 patients without it. RESULTS: In both groups the fibrinogen raised along the first six days of the AMI, however in the group with LIVT this level didn't raise as high as in the group without LIVT (p < 0.001). In the FDP evaluation two peaks were found, one at 48 hours and another on the 6 th day, but there were no differences between the two groups. The plasminogen values raised along the first week of AMI, in a similar way in both groups. CONCLUSIONS: a) Fibrinogen levels raises in AMI, but this elevation is significantly smaller in the group with LIVT, which suggests fibrinogen consume in fibrin formation of the thrombus. b) FDP and plasminogen levels raise along the first week of AMI, but in a similar way in the two groups. c) None of these parameters permitted to individualize patients with thrombus formation. PMID- 1290644 TI - [Treatment of heart insufficiency in the elderly with converting enzyme inhibitors]. AB - The main objectives of the treatment of Congestive Heart Failure are the improvement of quality of life and the reduction of mortality. Both are accomplished by the ACE inhibitors. The most important trials on the effect of ACE inhibitors on the improvement of the quality of life are reviewed. Trials about the reduction of mortality with ACE inhibitors are analysed. The sudden death problem was considered and so the relationship of this with ventricular arrhythmias. The recent evidence of a beneficial effect of captopril was reported. At last we analyse secondary effects of these drugs on the treatment of Heart Failure in old patients. PMID- 1290645 TI - [Persistent ductus arteriosus in the adult--report of a case]. AB - The authors describe a case of congenital heart disease no longer frequent in adults, due to an early diagnosis and surgical treatment. The patent ductus arteriosus in adults who received no therapy can present several forms of evolution, depending on its own hemodynamic profile. The present case is an example of a congenital heart disease not diagnosed during the childhood, that developed pulmonary hypertension and congestive heart failure. These clinical situations have a bad prognosis and place this patient in a group of high surgical risk. Thus, surgery is not advisable considering the bad prognosis and early high mortality rate. PMID- 1290646 TI - [What is the value of myocardial perfusion studies with isotopes in patients with complete left bundle branch block?]. AB - The prognosis of left bundle branch block is determined by associated cardiovascular disease. Exercise electrocardiography is not helpful in detecting ischemia in these patients. Exercise thallium-201 scintigraphy has been widely accepted for that purpose. The authors made an overview of several studies suggesting that exercise thallium-201 scintigraphy has low specificity regarding left anterior descending coronary artery disease. They also review the mechanisms of perfusion defects in patients with left bundle branch block without coronary artery disease. One important question to be clarified is weather small defects are unrelated to coronary artery disease. Finally the authors analyse a few methods to increase diagnostic accuracy of perfusion scintigraphy in left bundle branch block. First the employment of a new criterium that requires the apex to be abnormal to indicate left anterior descendent artery disease. Second Pharmacological Stress with Dipyridamole or Adenosine. Third imaging with Tc-99m MIBI. PMID- 1290647 TI - Ischemia, reperfusion and oxygen free radicals. AB - Alterations which occur during ischemia are reviewed. They modify the metabolic status in such a way they prepare the cell to an anomalous response to reoxygenation. The consequence of this disturbance is the generation of oxygen free radicals through several mechanisms, including the mitochondrial oxidative phosphorylation, the arachidonic acid cascade, the activation of xanthine oxidase, activation of phagocytes, iron mobilization, etc. Reduced glutathione is exhausted, proteins are inactivated. Lipid peroxidation induces membrane breakdown and cellular death. PMID- 1290648 TI - [Peri-ungual capillaroscopy in atherosclerosis]. AB - The pathology of the major vessels also affects microcirculation, making possible to evaluate at the distal sector the consequences of an ischaemia, due to an artery disease, for instance. This work had as its main aim to evaluate by peri ungueal capillaroscopy (PUC) the lesions due to an atherosclerotic process and the prognosis and/or diagnosis value of this exam. We studied 210 patients with either risk factors for atherosclerosis or atherosclerotic disease, who were divided into groups according to the severity of the lesions seen in PUC. Finally, we were able to conclude that although the capillaroscopic lesions found are not specific, they appear very early in the process and are more serious in the more severe cases. PMID- 1290649 TI - [Transthoracic and transesophageal comparative echocardiography in mitral valve prolapse]. AB - OBJECTIVE: Transthoracic and transesophageal comparative analysis of functional and morphological abnormalities associated to idiopathic mitral valve prolapse (MVP). DESIGN: Prospective study. SETTING: Outpatients with MVP diagnosis referred to echocardiographic laboratory of Cardiology Institute in Madrid, Spain. MATERIAL AND METHODS: In each case we analyzed by TTE and TEE, anterior, posterior and double localization of MVP, number of prolapsed mitral leaflets/patient, total area of MVP to mitral valve plane, mitral annulus diameter, total area and spatial distribution of mitral regurgitation. RESULTS: TEE diagnosed a greater number of prolapsed mitral leaflets and a greater percentage of double (80%) MVP. MPV area by TEE (50 +/- 31 mm2) was considerably larger (96 +/- 30 mm2) than TTE MVP area (50 +/- 31 mm3. Associated mitral valve regurgitation area calculated through TEE was larger (558 +/- 502 mm2) than the same parameter evaluated by TTE (450 +/- 515 mm2). CONCLUSIONS: TEE is an efficient technique in MVP non invasive diagnosis and particularly sensitive to posterior MVP. Our data could be helpful in MVP cases scheduled for mitral valve repairment. PMID- 1290650 TI - [Hypertensive reaction to exercise. Retrospective studies of 1363 consecutive exercise tests]. AB - OBJECTIVE: To study exercise hypertensive reaction and its relation with rest blood pressure, hypertension type and hypertensive cardiac disease. DESIGN: Retrospective study of treadmill exercise testes (ET) performed from January/89 to June/91: (n: 1703). SETTING: Stress tests Laboratory of Cardiology Service of a Military Hospital. METHODS: 1363 consecutive ET of male subjects, performing at least the 3rd stage of the Bruce protocol, were studied. From each ET record were obtained general data, including the reason for test, medication and the rest and exercise blood pressure. Exercise hypertensive reaction was defined as a Bruce protocol 3rd stage systolic blood pressure above 187 mmHg, which corresponds to mean +2SD of 130 normal male subjects previously studied. The Echocardiograms of non-treated hypertensives, obtained less than a month from ET, were reviewed. The diagnosis of borderline or moderate hypertension was base on the clinical records. RESULTS: 1) The 1363 ET included 132 (9.7%) ET to study hypertensive subjects, and 68 of these had hypertensive reaction. 86 ET were performed by non treated hypertensive subjects, of whom 73 had Echocardiogram. 43 (3.5%) from 1231 ET performed by non-hypertensive subjects also had exercise hypertensive reaction. 2) The left ventricular (LV) mass index of non-treated hypertensive patients had a positive correlation with exercise systolic pressure (r: 0.45; p < 0.001), more important than with rest blood pressure or exercise systolic pressure response; there was a relation with LV wall thickness, but not with internal ventricular dimensions, that was only observed in hypertensive subjects that also had hypertensive reaction to exercise. 3) Exercise systolic blood pressure was usually normal in borderline and elevated in moderate hypertensives (Qui2: 27.249; p < 0.001). 4) Subjects with exercise hypertensive reaction, but not previously diagnosed as hypertensives, were usually true hypertensives. CONCLUSIONS: 1) Hypertensive peaks seem to be an important determinant factor in LV hypertrophy of hypertension, but its influence is felt only above a certain blood pressure threshold; it results on LV concentric type hypertrophy. 2) Exercise systolic blood pressure had a discrimination power of about 80% to separate borderline and moderate hypertensive subjects. 3) All subjects having an exercise hypertensive reaction must be carefully observed, even if their blood pressure at rest is normal, because most of them are true hypertensive patients. PMID- 1290651 TI - [Infective endocarditis: analysis of 300 episodes]. AB - PURPOSE: Study of clinical features and etiologic agents, treatment and mortality of patients with infective endocarditis (IE). PATIENTS AND METHODS: 300 episodes of IE occurring in 288 patients, ages ranged between 0.2 and 78 (mean 30.76) years; 185 (62%) episodes occurred in males. RESULTS: a) etiologic agents: viridans group streptococci in 93 (31%) episodes, enterococci en 21 (7%), group D non enterococci in 19 (6%) (13 S. bovis), other streptococci in 14 (5%), Staphylococcus aureus in 59 (20%), Staphylococcus epidermidis in 14 (5%), gram negative bacteria in 16 (5%), gram-positive bacteria other than streptococci and staphylococci and staphylococci in 8 (3%), fungi in 4 (1%). The etiologic agents were not identified in 52 (17%) episodes; b) underlying cardiac diseases: valvular heart disease in 119 (40%) episodes, congenital heart disease in 37 (12%), prosthetic heart valves in 69 (23%), other heart diseases in 6 (2%). There was no evidence of previous heart disease in 69 (23%); c) treatment: surgical treatment was undertaken in 102 (34%) episodes. The frequency of surgical treatment in relation to the etiologic agents ranged between 1% (non-group D streptococcus) and 62% (negative blood cultures). The frequency of operation in relation to underlying heart disease ranged between 17% (other heart diseases), 19% (congenital heart disease) and 54% (prosthetic heart valve); d) mortality: 78 (26%) patients died, 56 (28%) of the 198 submitted to medical treatment and 22 (21%) of the 102 submitted also to surgical treatment. The mortality in the different groups of etiologic agents ranged between 5% (non group D streptococcus) and 62% (gram-positive bacteria other than streptococci ans staphylococci); in relation to the underlying with other heart disease, 19% in valvular heart disease patients, 21% in patients with congenital heart disease, 23% in patients without known heart disease and 43% in patients with prosthetic heart valves. CONCLUSION: The mortality associated with IE remains still high in spite of modern treatment; the mortality is different in relation to the cardiac status before the IE. PMID- 1290653 TI - Cholesterol embolization following coronary angioplasty. AB - Cholesterol emboli syndrome is an uncommon complication seen after an invasive vascular procedure or surgery in a patient with atherosclerotic disease. The obstruction of small arteries by cholesterol crystals may be responsible for its clinical features, such as livedo reticularis, "purple toe" syndrome, renal failure, involvement of the gastrointestinal tract, coronary arteries, central nervous system or the multiple cholesterol emboli syndrome. Certain laboratory abnormalities are frequently associated: an elevated erythrocyte sedimentation rate and eosinophilia, BUN and creatinine increase in the cases with renal failure and creatine phosphokines augmentation suggesting muscle involvement. Disseminated microemboli composed mainly of cholesterol crystals are the usual pathological findings. A case of cholesterol embolism occurring after left heart catheterization and percutaneous transluminal coronary angioplasty is reported. Twenty-four hours after the procedure, the patient developed purplish discoloration of toes and soles, livedo reticularis on lumbar region, buttocks and limbs, and renal failure. Patient did well two months after anticoagulant therapy. Prognosis of these cases is related to the extent of systemic involvement and the most significant impact on this syndrome can be made by its prevention. PMID- 1290652 TI - [Right infective endocarditis. Presentation of 3 clinical cases and review of the literature]. PMID- 1290654 TI - [Supraventricular tachycardia complicated by acute myocardial ischemia induced by atropine injection. Report of a clinical case]. AB - The authors report a case of supraventricular tachyarrhythmia complicated by severe myocardial ischemia after IV injection of Atropine in a 37 years old woman, without known coronary artery disease. She had an ECG with sinusal bradycardia (40/min) and she was on the waiting list for to be submitted to surgical intervention on the lumbar spine. PMID- 1290655 TI - [Role of pharmacologic stimulation with myocardial perfusion scintigraphy in the evaluation of patients with ischemic cardiopathy]. AB - Exercise myocardial-thallium scintigraphy plays a fundamental role in the diagnosis of coronary artery disease. Once exercise is not always feasible, pharmacological stress became a possible alternative. The authors review the mechanism of action, administrations protocols, indications and side effects of the drugs used for this purpose: dipyridamole, adenosine and dobutamine. Dipyridamole causes coronary hyperemia by increasing the interstitial levels of endogenous adenosine. Perfusion defects result from the mismatch of coronary reserve in different coronary territories. The drug administration is classically performed with a 0.142 mg/kg/min dosage e.v. for 4 minutes, total of 0.56 mg/kg. It is possible to use a greater dose of 0.84 mg/kg e.v. for 10 minutes, increasing sensitivity without loss of specificity for diagnosis of coronary artery disease. Oral dipyridamole protocols with 300 and 400 mg were used with similar results for sensitivity and specificity. The oral protocol has the disadvantage of delayed onset and longer action. Including several dipyridamole studies, 87% was obtained for sensitivity and 84% for specificity, in the diagnosis of CAD. Dipyridamole scintigraphy has been applied to myocardial infarction risk stratification, cardiac risk evaluation of patients proposed to noncardiac surgery and therapeutic efficacy evaluation of reperfusion techniques (angioplasty and surgery). The secondary effects of dipyridamole are frequent, however mild and well tolerated. They occur in half the patients, the most frequent, facial flushing (2%), dizziness (5%), nausea (4%), vomiting (1%), headaches (11%) and chest pain (26%). Some important complications were reported although rare: myocardial infarction, ventricular fibrillation and bronchospasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290656 TI - Relationship between ventricular arrhythmias and left ventricular false tendons in acute myocardial infarction. AB - To evaluate the association between left ventricular false tendon (LVFT) and ventricular arrhythmias in acute myocardial infarction (MI) on the 1-st day of acute MI 71 patients were examined by 24-hour ECG-monitoring and M-mode, two dimensional, Doppler echocardiography. LVFT was detected in 30 patients (42.3%). The frequency of left ventricular fibrillation, the number of patients with multiform ectopic ventricular beats (EVB), the number of single and pair EVB and runs of ventricular tachycardia were greater in group of patients with LVFT. 37 patients had Lown grades 1-2 (A) of arrhythmias, 34 patients had grades 3-5 (B). LVFT was revealed in four patients in group A (10.8%) and in 27 patients in group B (76.5%, p < 0.001). There were no significant differences between groups in left ventricular asynergy area and wall motion score, left and right ventricular, left atrium dimensions, left ventricular contractility indices, left ventricular walls thickness, frequency of mitral regurgitation. Multifactor analysis has shown significant relationship between Lown's class value and LVFT (p < 0.0001), Lown's class and arterial hypertension (p = 0.0376). Other 17 clinical factors were not connected with Lown's class value. Thus, LVFT was associated with severe ventricular arrhythmias in patients with AMI. This fact can be used as a predictor of these disturbances. PMID- 1290657 TI - Tribute to Professor Keiichi Tanaka, a scientist and an artist. PMID- 1290658 TI - Scanning electron microscopic observations of the immunodefensive systems with special reference to the surface morphology of the non-lymphoid cells. AB - This paper reviews scanning electron microscopic observations of cellular elements forming various lymphoid organs. The reticular cells in the secondary lymphoid organs are stellate, smooth-surfaced forms extending slender processes to comprise a three-dimensional network. The reticular fibers are usually covered by reticular cell processes, though they are naked in certain regions. Other types of reticular cells are observed in certain places: the "retothelial" type in the lymphatic sinus of the lymph nodes, and the "follicular dendritic" type in the germinal center of various lymphoid organs. The thymic epithelial cells are divided into two main types: stellate cells which form a three-dimensional meshwork throughout the thymus parenchyma; and large vacuolated cells located in the medulla. A continuous single layer consisting of the processes of the stellate epithelial cells separates the parenchyma from the connective tissues of the capsule, septa and vessels. The M cells in the epithelium of the gut associated lymphoid tissues (GALTs) are cells with numerous irregular microprojections on the luminal surface. They often attach microorganisms to the luminal surface, reflecting their functions of antigen transport into the underlying lymphoid tissue. Lymphocytes of various shapes often cluster in the intercellular spaces under the M cells, a phenomenon believed to indicate direct stimulation of lymphocytes by certain transported substances. Macrophages are amoeboid cells independent of and unable to transform into reticular and endothelial cells, at variance with prerequisites of the reticulo-endothelial system concept. Multiple features of macrophages probably reflect the presence of the subpopulations as well as the phases of their activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290659 TI - The myoepithelial and basal cells of ducts of human major salivary glands: a SEM study. AB - The cytoarchitecture and distribution of myoepithelial (mecs) and basal (bc) cells of intralobular (intercalated, striated) and interlobular (excretory) ducts of human major salivary glands were studied by SEM through a variety of maceration and microdissection techniques. Intercalated ducts are covered by mecs which, unlike the large stellate cells of acini, are spindle shaped. Small star shaped mecs are rarely observed even in the most distal striated ducts, while no such cells are seen in excretory ducts. Basal cells form a more or less continuous row of small, basally placed cells in excretory ducts. Sparse bc are occasionally present in proximal striated ducts as well. Following microdissection, bc exhibit a cup-shaped apex which embraces the convex base of principal cells. This configuration may explain why, in TEM, bc seem to possess lateral processes which may be mistaken for mecs processes. Moreover, the lateral surfaces of bc do not exhibit the complex system of plasmalemma folds typical of principal cells. The present study demonstrates that fusate mecs are present in intercalated ducts and that basal cells are distinct from myoepithelial cells. These results may have some relevance in histogenetic studies of salivary gland neoplasms. PMID- 1290660 TI - Scanning electron microscopy of the small intestine during gluten-challenge in celiac disease. AB - The celiac disease syndrome is characterized by structural and ultrastructural alterations of the small intestine mucosa. According to criteria by European Society of Paediatric Gastroenterology and Nutrition, the conclusive diagnosis of celiac disease in children depends on the demonstration of histological relapse of the mucosa after reintroduction of gluten in the diet, as this syndrome is a permanent condition of gluten intolerance. Under these diseased conditions, the structure of the intestinal villi has been studied by light microscopy; morphological alterations were revealed only when the gluten challenge induced a clinical relapse. Scanning electron microscopy analyses of the intestinal mucosa in celiac diseased patients showed a strikingly uniform destruction of the villi with changes in their dimensions and arrangement. At high magnification the enterocytes were irregular in size and shape with a decrease and disruption of the glycocalyx. Reductions in length and density of microvilli were also clearly identified. Although these scanning electron microscopy findings could not demonstrate a relationship between the degrees of mucosal atrophy and the duration of the gluten challenge, they nevertheless revealed early stages of fine villous alterations that cannot be detected by the presently employed low resolution light microscopic techniques. PMID- 1290661 TI - The "limiting ridge" of the rat stomach. AB - In the rat, the forestomach is separated from the glandular stomach by a fold of the forestomach mucosa which generates the "limiting ridge" on the inner surface of the organ. This ridge overlaps a deep groove which is flanked proximally by the forestomach and distally by the glandular stomach. Light microscopy and scanning electron microscopy reveal that the keratinized squamous epithelium of the forestomach merges into the columnar epithelium of the glandular stomach at the bottom of the groove. Among the columnar cells of the distal wall of the groove are numerous brush cells. A remarkably thick lamina muscularis mucosae extends deep into the ridge. The peculiar architecture of the "limiting ridge" and the presence of numerous brush cells in its distal wall suggest that the region not only represents the transitional zone between forestomach and glandular stomach but that it might have a more specific function. PMID- 1290662 TI - Ultrastructural features of the rabbit proximal tubules. AB - The unique ultrastructure of the epithelial cells that line the entire length of the proximal tubule have been described. In particular, scanning electron microscopy has been used to illustrate the varied nature of the apical, lateral and basal surfaces of cells located along P1, P2 and P3. The functional implication of the highly specialized microanatomy of the basal cell surface remains an interesting area of investigation. PMID- 1290663 TI - Three-dimensional visualization of renal cells by NaOH maceration. AB - The three-dimensional fine structure of cells composing the renal tissue was demonstrated by SEM after the removal of extracellular matrices by NaOH maceration. This paper focuses on glomerular mesangial cells, Goormaghtigh's cells (extraglomerular mesangial cells), and epithelial cells in the thin limbs of Henle's loop in the rat, rabbit and dog. Mesangial cells reveal rough surfaces covered with short microvilli. The cells extend long branching processes in close association with the glomerular capillary, suggesting a role for them of regulating the capillary caliber. The mesangial cells interdigitate with each other by their microvilli, forming an intercellular labyrinth. Goormaghtigh's cells at the glomerular hilus are also covered with microvilli, which form narrow labyrinthine spaces between the cells. The labyrinth among the mesangial cells and that among Goormaghtigh's cells connect with each other at the hilus, giving rise to a channel system leading from the periphery of the glomerulus through the hilus to the interstitial space outside the glomerulus. Renal tubule cells display complicated intra- and intercellular interdigitations on the basal aspect. The pattern of epithelial interdigitation is specific to each tubular segment. The descending and ascending thin limbs of the long loops demonstrate a striking contrast to each other. The former is characterized by moderate intercellular interdigitation and by numerous microvilli on the lateral and basal surfaces; the latter is marked by elaborate, pectineal interdigitations, and by smooth basolateral surfaces. PMID- 1290664 TI - The interface between epithelium and lamina propria in the rat urinary bladder. AB - We investigated by transmission and scanning election microscopy the interface between the epithelium and lamina propria in the rat urinary bladder. A digestion technique that dissolves the basal laminae and collagen fibrils was effective in cleaving the mucosa at this level; the specimens were then prepared for scanning electron microscopy, thus visualizing the basal epithelial surface and the uppermost surface of the lamina propria. The underside of the epithelium is scored by very numerous grooves which in the intact organ are occupied by a dense network of blood capillaries. These vascular grooves allow a large number of capillaries (epithelial capillaries) to run at a distance of a few tenths of a micron from the epithelium. On the side of the lamina propria, after collagen and other extracellular materials had been removed, the capillary network itself is visible in the uppermost region. The network is complementary to that of vascular grooves. Other smaller grooves on the basal surface of the epithelium correspond to nerve fibres which run within a few tenths of a micron from the epithelium. PMID- 1290665 TI - Three-dimensional analysis of the atrophic process of rat seminiferous tubules after estradiol treatment. AB - Atrophic changes in the basal portion of the seminiferous tubules caused by daily injections of estradiol have been found by scanning electron microscopy disclosed after a digestion technique using collagenase and trypsin. In the control rat, the smooth basal portion of the epithelium was composed of polygonal Sertoli cells and reticularly-arranged ovoidal spermatogonia. After estradiol treatment, there appeared wavy furrows and ridges, and many folded micro-wrinkles in the complicated basal portion of the seminiferous tubules. The wavy furrows and ridges were repeatedly formed and appeared just like a cornice. These structures ran in an orderly manner perpendicular to the longitudinal axis of the tubules. In contrast, many micro-wrinkles ran in parallel to the longitudinal axis. These two structures had a characteristically similar size and orderly arrangement. They are discussed in relation to the mechanism by which the seminiferous tubules shrink by injections of estradiol. PMID- 1290666 TI - Towards high resolution SEM of biological objects. AB - The major task of biological high resolution SEM and TEM is to provide structural information for correlating structure and function. It is the only methodology with the inherent power needed to observe structures down to molecular dimensions within the context of complex biological systems. Specimen preparation and imaging techniques should therefore be directed towards the preservation and imaging of the smallest significant details in order to fully exploit this unique, integrating feature of biological electron microscopy, complementing the progress of the techniques used in cell biology, biochemistry, and molecular biology. PMID- 1290667 TI - The three-dimensional architecture of the myosalpinx in mammals: an anatomical model for a functional hypothesis. AB - Direct visualization of the three-dimensional architecture of the tubal musculature (myosalpinx) was made possible by a technique involving chemical digestion of interstitial connective tissue, followed by ultrasonic microdissection and final observations under the scanning electron microscope. The isthmic myosalpinx in the guinea pig, rabbit and in humans consists of muscular bundles that tend to lie longitudinally, circularly or oblique. The muscular bundles along the tubal wall change direction, branch and intermingle with one another, giving rise to an irregular network in which distinct layers are not readily distinguishable. In the ampulla, the muscle bundles form a very irregular three-dimensional network of fibres that follow different orientations. The authors suggest a primary role for such a structure in the random pendular transport of the gametes as well as in the denudation of the egg by deformation of the myotubal wall. PMID- 1290668 TI - Scanning electron microscope investigations on the vaginal epithelium of the guinea pig during the estrous cycle. AB - The present scanning electron microscope investigation describes the morphological changes occurring on the apical surface of the guinea pig vaginal epithelium during the estrous cycle. Dramatic changes can be observed at estrus in which the surface of the vaginal epithelium is covered by a distinct layer of mucous cells. PMID- 1290669 TI - SEM studies on unmanageable hair. AB - The manageability of the hair is dependent on the surface composition of the hair shaft. Exogenously caused damage leads to unmanageability by massive superficial defects in the hair cuticle. The symptoms of trichorrhexis nodosa and trichoptilosis are present, and superficial horny scales are bent up and curve under in tunnel-like fashions. Appropriate hair care can improve these defects. Endogenous damage to the hair leading to unmanageability is characterized by spiral furrows along the shaft. It can not usually be improved by the use of care products. The examples presented in the paper demonstrate that exogenous and endogenous causes of unmanageability are characterized by different alterations in the hair shaft. PMID- 1290670 TI - Ultrastructural organization of two tapetal types in angiosperms. AB - The development of preparation techniques that include freeze fracturing provide an ideal method for studying the differentiation of plant tissues in the scanning electron microscope. This is illustrated with reference to tapetal development in Catananche caerulea, which has a plasmodial tapetum, and in Lolium perenne, which has a secretory tapetum. PMID- 1290671 TI - The maceration technique in scanning electron microscopy of collagen fiber frameworks: its application in the study of human livers. AB - This paper reviews the cell-maceration/scanning electron microscopic (SEM) technique and its application in the study of human livers. The maceration of glutaraldehyde-fixed tissues with 2N-NaOH and water at room temperature effectively and consistently removes all the cells, thus exposing collagen fiber networks. SEM of the macerated tissues shows three-dimensional arrangements of collagen fibers more clearly than previously reported methods. High resolution SEM observations of macerated and non-macerated collagen fibrils of the rat tail tendon have revealed that both show similar cross-striated bandings that are determined by an alternate succession of elevated and depressed segments along the collagen fibrils, with a period of approximately 65 nm. Three ridges have been observed in the nonmacerated collagen fibrils: two on the margins of the elevated segments and one at an intermediate point of the depressed segment. The macerated collagen fibrils show a straight arrangement with slightly wavy microfibrils. The subendothelial spaces of Disse in the human liver contain abundant collagen fibers. There are some collagen fibers that stretch between adjacent collagen fiber sheaths in the subendothelial spaces of Disse, either forming a mono-layered network or coursing individually. The collagen fibers in the spaces of Disse are continuous with those in the liver capsule and in the Glisson's sheaths and with those around the central and sublobular veins. The collagen fibers in human livers form a network of the liver as a whole, thus constituting a hepatoskeletal system. PMID- 1290673 TI - On the molecular profiling of cell surfaces by SEM. AB - Cell surfaces interface with a variety of environments and, as a consequence, cell surface properties are of considerable functional importance to the biological organism. SEM immunocytochemistry (SEM-IC) is one of a range of techniques used to analyse cell surface properties. A major goal of SEM-IC centres on extended survey or high-magnification morphological analysis of cell and tissue surfaces combined with molecular profiles of these surfaces as established by gold-labelling. The properties of colloidal gold make it the marker of choice for SEM-IC and a representative gold-labelling protocol is outlined. The SEM-IC gold-labelling technique has been applied advantageously to the analysis both of cell surfaces and cytoskeletal and extracellular matrix elements: a tabulation of the main SEM-IC biomedical applications is given. Illustrated examples demonstrate how SEM-IC provides a highly effective approach for analysis both of cell and tissue differentiation-maturation sequences, and of pathological change involving not only the entire tissue or cell surface but also minute changes in microdomain characteristics of the individual cell surface. Steps in exploiting the technique of colloidal gold SEM-IC have been several-fold and include: use of backscattered electron imaging; accurate localization of gold particles by superimposition on topographical maps of the cell surface; and use of small (1-10 nm) gold probes followed by silver enhancement in order to minimize steric hindrance. Factors under assessment include: use of low voltage SEM; BE imaging of samples coated with ultrathin metal films; and use of gold labelled SEM-IC for direct quantification of the numbers of target molecules exposed on cell surfaces by automated image analysis of the digitized BE image. PMID- 1290672 TI - A modified method for vascular casting and scanning electron microscopy: its utility in the demonstration of rat pancreatic insulo-acinar and other blood vascular systems. AB - Monomeric methyl methacrylate resin, supplemented with 1.0% benzoyl peroxide and 1.0% N, N-dimethyaniline, enables good vascular casts useful for scanning electron microscopy when the injected organs or tissues are promptly heated in a microwave processor. The details of this vascular casting and scanning method are described with a clear demonstration of the rat pancreatic blood vascular bed, in particular, its intralobular, extralobular and translobular insulo-acinar portal systems and other vascular routes, including the insulo-venous vessels, which are sinusoidal in nature. PMID- 1290674 TI - Scanning tunneling microscopic (STM) analysis of the phospholipid bilayer surface characteristics in the P beta phase. Secondary ripples. AB - Previous investigations have elaborated on the necessity for dimyristoylphosphatidylcholine (DMPC) molecules to conform in a ripple phase at the temperature intermediate between the transition and pretransition in order to protect the hydrophilic-hydrophobic polarity of the bilayer. Present observations, in addition to the asymmetric P beta phase of 11.1 +/- 1.3 nm wave length, demonstrate orthogonal corrugations perpendicular to the main wave direction. Whether this is a prerequisite for maintaining the molecular order disorder balance at such specific temperature, or it results from yet unknown source is unclear at present. PMID- 1290675 TI - Complementary scanning electron microscopy: technical notes and applications. AB - This report introduces practical techniques and applications of complementary scanning electron microscopy (SEM). To identify the complementary structures at high magnification, we first made a montage pair of low magnification micrographs as a guide map. Consulting the map, we took complementary micrographs at high magnification. When taking a picture at high magnification, we drew the outline of the most prominent structures on a transparent plastic plate attached to the cathode-ray tube of a SEM. Then another picture of the complementary structures was taken after adjusting the complementary structures to the reverse image of the plastic plate. We performed three applications of the complementary SEM: 1) complementary observation of the epithelial underside and lamina propria of the rat urinary bladder; 2) complementary observation of the fractured Golgi apparatus; and 3) evaluation of specimen drying methods. After proper digestion of the rat urinary bladder using strong alkali, the epithelium was detached from the underlying lamina propria. On the basal side of the epithelium, the meshwork of grooves were visible. The observation of the corresponding lamina propria confirmed that the grooves were occupied by blood capillaries located in the uppermost part of the lamina propria. The complementary observation of the Golgi apparatus was useful for understanding its three-dimensional architecture. The observation on both complementary fractured surfaces of the Golgi apparatus from the mouse lacrimal gland demonstrated the continuity of the Golgi stacks. It was also effective for observing both the cis and trans side of the same Golgi stack. Complementary SEM was also useful for evaluating the specimen drying method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290676 TI - Preparation of human chromosomes for high resolution scanning electron microscopy. AB - The addition of ethidium bromide during the last 2.5-3 h of lymphocyte culturing restricted chromosome contraction and preserved the banding structure in scanning electron microscopy. Treatment of the chromosomes with trypsin and use of impregnation with osmium tetroxide and thiocarbohydrazide resulted in a structural preservation of high resolution quality. PMID- 1290677 TI - Human fibroblast intracellular network prepared with digitonin for field emission scanning electron microscopy. AB - Results obtained by extracting human fibroblast cells for the study of cytoskeletal structures are compared. Cells grown in culture were treated with digitonin in contrast to other methods of detergent preparation using Triton and Saponin. The three dimensional intracellular network which resulted from digitonin treatment was found to be similar in appearance to the structures observed by high voltage transmission electron microscopy of untreated cells described as a microtrabecular lattice by Porter and Tucker (1981). Our results, obtained by high resolution, field emission scanning electron microscopy indicate that the microtrabecular lattice may indeed be one conformation of a dynamic cytoskeleton. PMID- 1290678 TI - Intussusceptive microvascular growth: a common alternative to capillary sprouting. AB - Intussusceptive capillary growth represents a new principle for microvascular growth as described in the lungs of growing rats. According to this concept, the capillary network expands by the formation of slender transcapillary tissue pillars, which give rise to new vascular meshes. The process was first observed in Mercox casts of the lung microvasculature, which revealed the existence of multiple tiny holes with diameters around 1.5 microns. Consecutive transmission electron microscopic investigation of serial sections demonstrated that the holes corresponded to slender tissue pillars (Burri and Tarek, 1990). The corrosion cast technique thus appears to be an adequate screening method for intussusceptive growth. In the present investigation, Mercox casts of various vascular systems, namely, those of the eye, submandibular gland, heart, liver, stomach, small and large intestine, trachea, kidney, uterus and ovary were prepared from rats aged between 4 and 9 weeks in order to screen them for the existence of the typical tiny holes representing tissue pillars. In all organs investigated, these structures were observed in various locations to a variable degree. They were mainly encountered within dilated vascular segments or at triple or quadruple branching points of the circulation. Even in capillary networks with a three-dimensional arrangement could these pillars be detected. Intussusception thus appears to be a principle of growth appertaining to many vascular systems. PMID- 1290679 TI - Three-dimensional architecture of pericytes with special reference to their topographical relationship to microvascular beds. AB - Microvascular beds and pericytes in the submandibular gland, thyroid gland and heart were studied by combined scanning electron microscopy and chemical digestion. The submandibular gland had a relatively loose network of blood capillaries, the thyroid gland possessed a close-meshed network of capillaries, and those in the myocardium ran parallel to the long axis of myocardial cells. The thyroid gland exhibited the largest numbers of pericytes. Three types of pericytes could be distinguished by their shape and localization. Type I pericytes, which were confined to true capillaries, had a fusiform or polygonal cell body, a few long, slender longitudinal processes (primary ones) and short, fine circumferential processes (secondary ones). Type II pericytes, which were found in the arterial side of myocardial capillaries, were characterized by large, circumferential band-like processes completely encircling the vessel. Type III pericytes, which were seen on the venous side of thyroid and myocardial capillaries, had a flattened cell body and short, irregular processes. Type II and III pericytes appear to show an intermediate or transitional form between smooth muscle cells and typical pericytes (Type I). Judging from the configuration of pericytes suggests that these are related to functions such as contraction as well as mechanical support. PMID- 1290680 TI - Three-dimensional ultrastructure of the autonomic nerve terminals in the lamina propria mucosae of the rat large intestine. AB - The three-dimensional ultrastructure of the autonomic nerve terminals in the lamina propria mucosae of the rat large intestine was studied by scanning electron microscopy using the KOH-collagenase digestion method as well as by transmission electron microscopy. Observations showed unmyelinated nerves in the lamina propria mucosae as well developed just above the muscularis mucosae and forming a two-dimensional irregular network by anastomosing with one another. Each nerve in the network consisted of axons and Schwann cells. The axons were about 0.1 micron in diameter and had local swellings (about 0.2-0.5 microns diameter) along their course. Transmission electron microscopy revealed the presence of synaptic vesicles in these varicosities. Although some of the axons left the Schwann cell processes to run separately, most of them twined around or were embedded in the Schwann cell bodies or processes. Blind ends of axons were only occasionally observed in the nerve network. These findings suggest that the network of the unmyelinated nerves itself represents a terminal apparatus acting upon the muscular and glandular cells. PMID- 1290681 TI - Changes in size and shape of smooth muscle cells from the portal vein of spontaneously hypertensive rats: an ultrastructural analysis. AB - The portal vein was investigated in male spontaneously hypertensive rats (SHR), from Wistar-Kyoto (WKY) and Wistar strains, in animal 16-20 weeks old. In SHR, the inner circular smooth muscle was unchanged, but the outer longitudinal layer showed marked alterations in shape and size, readily observed in three dimensional micrographs using scanning electron microscopy. The cells in both Wistar and WKY were elongate and tubular with little variation along their lengths and with a relatively smooth sarcolemma. This applied to both the inner and outer layers of smooth muscle. In contrast, the smooth muscle cells from SHR in the outer layer varied considerably in thickness along their lengths, and had very irregular outlines with numerous pits or depressions of varying sizes. In addition, the cells frequently had major forks or branches. The vasa vasorum running through the muscle layer, fibroblasts and nerve bundles were also identified. Sectioned material (transmission electron microscopy) showed a change in shape and hypertrophy of the smooth muscle cells from the portal vein of SHR, and also demonstrated a significant increase in paracellular connective tissue in the outer layer of smooth muscle. Such major morphological alterations in the outer layer of smooth muscle in the portal vein from SHR could have profound effects on functional studies. PMID- 1290682 TI - New insight into the nature of scrapie from old radiation results. PMID- 1290683 TI - Pharmacokinetics and subcellular localization of radiosensitizers. PMID- 1290684 TI - The frontiers of time-resolved measurement. PMID- 1290685 TI - Inadequate vasculature in solid tumours: consequences for cancer research strategies. AB - In the last decade, since we first postulated that antiproliferating endothelial therapy was a promising new approach to therapy, there have been remarkable developments. Vascular effects have been recognized from completely unrelated and unexpected agents, including hyperthermia, photodynamic therapy, misonidazole, tumour necrosis factor, FAA, interferon and interleukins. These vascular effects may coexist with direct cytotoxicity to the tumour cells or they may explain all of the antitumour activity. In order to benefit from such vascular effects, we need to monitor them, understand their mechanisms of action and ensure that the clinical scheduling is optimized to give the greatest therapeutic advantage. The biologist must re-evaluate the validity of his or her tumour models and the clinician must question whether drugs targeted at tumour cells should be sought or whether it would be more productive to target the nutrient supply through the neovasculature. The molecular biology approaches of oncogene expression in tumour cells and growth factor dependency must be weighed against angiogenesis, the pathophysiology of the tumour mass and its supporting normal stromal elements. Since this is a highly complex field there will be many fascinating years of work elucidating tumour versus normal vascular differences. In the meantime, we need to ensure that we do not reject useful therapeutic agents by inappropriate scheduling based on a misunderstanding of their mode of action, or by the use of inappropriate models for testing potential anticancer agents. PMID- 1290686 TI - Pharmacological manipulation of blood flow. PMID- 1290687 TI - Endothelial cells in tumours: the challenge. PMID- 1290688 TI - Can 31P magnetic resonance spectroscopy measurements of changes in experimental tumour metabolism be related to modification of oxygenation status? PMID- 1290689 TI - Hypoxia as a determinant factor in radiotherapy? Where are we? PMID- 1290690 TI - Intrinsic radiosensitivity as a predictor of patient response to radiotherapy. PMID- 1290691 TI - Cell kinetics: from tritiated thymidine to flow cytometry. PMID- 1290692 TI - The future of flow cytometry. PMID- 1290694 TI - In vivo labelling of human tumours with bromodeoxyuridine: a histopathologist's view. PMID- 1290693 TI - Cell kinetics of human solid tumours. PMID- 1290695 TI - ARCON: accelerated radiotherapy with carbogen and nicotinamide. PMID- 1290696 TI - From laboratory to clinic. PMID- 1290697 TI - Early processes in radiation-induced DNA damage. PMID- 1290698 TI - Post-irradiation modification of normal-tissue injury: lessons from the clinic. PMID- 1290699 TI - Modelling altered fractionation schedules. PMID- 1290700 TI - Kinetics of accelerated repopulation in normal and malignant squamous epithelia during fractionated radiotherapy. PMID- 1290701 TI - Accelerated fractionation using the concomitant boost: a contribution of radiobiology to radiotherapy. PMID- 1290702 TI - Fast neutron radiotherapy. PMID- 1290703 TI - Tumour radiosensitization with the halogenated pyrimidines 5'-bromo- and 5' iododeoxyuridine. PMID- 1290704 TI - Oncogenes and tumour suppressor genes in human cancers: clinical implications. PMID- 1290705 TI - Radiotherapy in developing countries. PMID- 1290706 TI - Shouldered survival curves in accordance with the unsaturated rejoining kinetics of DNA double-strand breaks. PMID- 1290707 TI - Interaction of hydrogen peroxide and ionizing-radiation-induced damage. PMID- 1290708 TI - The role of charge in intracellular radioprotection by thiols. PMID- 1290709 TI - Defective response of radiation-sensitive mutants to anisotonic shock. PMID- 1290710 TI - Molecular analysis of radiation damage and repair in normal and mutant cells. PMID- 1290711 TI - DNA lesions: linear energy transfer and radiosensitive mutants. PMID- 1290712 TI - Radiation-induced DNA damage in relation to linear and quadratic terms of dose effect relationships for cell reproductive death. PMID- 1290713 TI - The nature of the initial slope of radiation cell survival curves. PMID- 1290714 TI - Fluorescence in situ hybridization: an improved method of quantitating chromosome damage and repair. PMID- 1290716 TI - Is the micronucleus assay predictive for cellular radiosensitivity? PMID- 1290715 TI - Single-cell microgel electrophoresis: an in vitro assay of radiosensitivity. PMID- 1290717 TI - Does induced repair determine the lethal effects of very low radiation doses? PMID- 1290718 TI - Tumour cell kinetics and heterogeneity: insights from multicell spheroids. PMID- 1290719 TI - Biological targeting of radionuclides. PMID- 1290720 TI - The case of the impure mouse. PMID- 1290721 TI - Antitumor effect of a Coliolus preparation, PSK: induction of macrophage chemotactic factor (MCF) in spleens of tumor bearing mice. AB - The effect of administration of PSK (Polysaccharide Kureha), a Coliolus preparation, in Meth-A solid tumors was analyzed in BALB/c mice. Spleen cells prepared from normal, non-treated Meth-A bearing, PSK-treated normal and PSK treated tumor bearing mice were examined for induction of macrophage chemotatic factor (MCF). Only spleen cells from the latter mice produced MCF after 48 hrs of cultivation in the presence of Meth-A cells or concanavalin A (Con A). MCF producing cells were indicated to be Lyt-1 positive, L3T4 positive and Lyt-2 negative cells in the negative elimination assay. There were no differences in the production of other cytokines including interleukin-2, interferon and tumor necrosing factor, spleen cells obtained other different groups of mice. The antitumor effect of either crude or purified MCF (molecular weight 100,000) was examined by daily consecutive intratumoral injections into Meth-A tumor tissues, and a significant inhibitory effect was detected. PMID- 1290722 TI - Systemic IL-1 and adjuvant treatment of an experimental tumor. II. Immune status during primary tumor challenge. AB - In this investigation, systemic administration of interleukin-1 (IL-1) and local adjuvant therapy were shown to modify immunological parameters associated with the lymphatics draining the site of experimental tumor inoculation. These immunological parameters were shown to be modified early (within 7 days) following tumor inoculation and within the time period of IL-1 administration. IL 1 induced a marked increase in the number of lymphocytes within the brachial and axillary lymph nodes associated with the tumor inoculation site. This increase was characterized by an overall augmentation in the number of CD8+ and CD4+ lymphocytes. In vitro, these lymph node cells showed enhanced proliferation in response to interleukin-2 (IL-2) when compared to non-IL-1 treated animals, and were capable of mounting a potentially greater cytotoxic response for both NK sensitive and NK resistant tumor targets. Without IL-1 administration, temporal and sequential lymph node cellular changes were observed, but were diminished and delayed when compared to the IL-1 treated animals. By adoptive transfer of tumor resistance, lymph node cells from IL-1 treated animals were demonstrated to be tumor-protective in vivo. These results demonstrate that systemic IL-1 induces regional changes in the lymphatics of mice undergoing primary tumor challenge with adjuvant therapy and that these changes result in tumor protection for the host. PMID- 1290723 TI - Interferon-alpha, interferon-gamma and sizofiran in the adjuvant therapy in ovarian cancer--a preliminary trial. AB - The study included 24 cases of negative second-look laparotomy (SLL) after operation on ovarian cancer. 12 cases were treated with sizofiran and recombinant interferon-gamma before and after SLL and then with human lymphoblastoid interferon-alpha. The remaining 12 cases (controls) were followed up without any drug therapy after SLL. There were no recurrences in the treated group, but in 3 cases of the control group. Also significant difference in survival was noted in the treated group. PMID- 1290724 TI - Lymphocyte responses to food antigens in food sensitive patients with allergic tension-fatigue syndrome. AB - Scores of radioallergosorbent test (RAST) for cow's milk or buckwheat flour and proliferative responses of peripheral blood mononuclear cells (PBMCs) to bovine serum albumin and beta-lactoglobulin or buckwheat flour were measured in cow's milk or buckwheat flour sensitive patients with allergic tension-fatigue syndrome. In all 3 cow's milk sensitive patients with allergic tension-fatigue syndrome, RAST scores for cow's milk were negative or slightly positive, but PBMCs well responded to bovine serum albumin and beta-lactoglobulin, but not to ovalbumin. In a buckwheat flour sensitive patient with allergic tension-fatigue syndrome, RAST scores for buckwheat flour were negative, but PBMCs well responded to buckwheat flour, but not to ovalbumin, bovine serum albumin and beta lactoglobulin. Conversely, in cow's milk or buckwheat flour sensitive patients with immediate allergic symptoms, RAST scores for offending foods were positive although PBMCs did not respond to offending food antigens. These results suggest that proliferative responses of PBMCs to food antigens are very useful for detection of offending foods in allergic tension-fatigue syndrome. PMID- 1290725 TI - Effect of pyridoxine on tumor necrosis factor activities in vitro. AB - Clinical trials with tumor necrosis factor (TNF) as an antitumor agent have so far given rather disappointing results. In this study we show that the naturally occurring vitamin B6 compound, pyridoxine, enhances TNF-induced cytolysis of three subclones of a mouse fibrosarcoma cell line (WEHI 164). The degree of pyridoxine-induced enhancement of TNF cytotoxicity seems to be dependent on the cells sensitivity to TNF, as the enhancement was much more pronounced in the relatively TNF resistant subclone act-R(cl.12)-WEHI 164, than in the very TNF sensitive subclone WEHI 164 clone 13. Furthermore, our study shows that pyridoxine, in contrast to its enhancing effect on TNF-induced cytotoxicity, rather inhibits TNF-induced growth of human FS-4 fibroblasts. Pyridoxine also enhances lymphotoxin (LT)-induced tumor cell killing and inhibits LT-induced fibroblast growth. Pyridoxine is a relatively non-toxic agent in vivo. Our results suggest that a combination of TNF and pyridoxine may be more efficient than TNF alone, in the treatment of cancer patients. PMID- 1290727 TI - Women are different, but not that different. PMID- 1290726 TI - Frozen-thawed human blood monocytes respond reproducibly to activation stimuli: implications for screening of BRMs. AB - The purpose of this study was to identify the optimal freezing conditions for human blood monocytes to allow their recovery and use for in vitro screening of activation stimuli. Human monocytes separated from buffy coats of healthy blood donors were suspended at a density of 1 x 10(7) cells/ml in freezing medium consisting of 70% medium: 20% fetal bovine serum: 10% DMSO frozen in a stepdown freezer, and stored at -180 degrees C. Monocytes were thawed at different times up to 4 months later. Viability was > 90%. Fresh monocytes from different donors and frozen monocytes thawed at different times were incubated with different concentrations of lipopolysaccharide, muramyl tripeptide, muramyl dipeptide, or lipopeptide. Tumoricidal activity and IL-1 production of fresh monocytes varied greatly among the 5 different preparations. In contrast, the frozen monocytes (thawed at different times) produced uniform levels of antitumor activity and IL 1 production. These results show that monocytes recovered from frozen storage maintain their ability to respond to activation stimuli in a uniform and reproducible manner. Thus, the use of frozen-thawed monocytes is recommended for screening of macrophage-activating agents. PMID- 1290728 TI - Anticoagulant therapy and direct current cardioversion of patients with atrial fibrillation or atrial flutter. PMID- 1290729 TI - A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis. AB - The elderly (age > 65 years) are more vulnerable to side-effects induced by non steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs. PMID- 1290730 TI - Tolerance and long-term efficacy of a fixed combination of atenolol and nifedipine in the treatment of angina pectoris. Stuart Clinical Research Group. AB - To monitor the tolerance and long-term efficacy of a low-dose fixed combination of 50 mg atenolol and 20 mg nifedipine (slow release formulation) in patients with stable angina pectoris, 157 patients received treatment twice daily in a multi-centre, open-label fashion for periods up to 12 months following a four week run-in period on atenolol 50 mg twice daily. A total of 122 patients completed the study and had data from all treatment visits. In these patients the median number of weekly anginal attacks was halved, compared to the run-in period on atenolol alone following one month's fixed combination treatment, and this benefit was maintained throughout the 12-month study period. In addition, GTN consumption similarly declined on the fixed combination in comparison with the run-in period. Treatment with the fixed combination was not associated with any long-term increase in the frequency of reported side-effects or adverse biochemical changes compared to run-in. The fixed combination of atenolol 50 mg and nifedipine 20 mg reduced anginal frequency and GTN consumption compared to atenolol alone without causing any increase in adverse effects. PMID- 1290731 TI - The role of early surgery following myocardial infarction. European Coronary Surgery Bypass Group. AB - This co-operative study was a prospective randomised study to evaluate the role of coronary bypass surgery following acute myocardial infarction. The criterion for entry was an early positive exercise tolerance test. All patients who satisfied the clinical criteria of acute myocardial infarction but who were excluded had information on survival obtained after two years. A total of 4658 patients were assessed, with 3334 (71%) having a modified exercise test. This test was positive in 728 patients, of whom 598 then underwent coronary angiography. Three hundred and forty-eight patients were randomised (surgery 168, continuing medical treatment 180). At two years the survival in the medical group was 96% and in the surgical group was 93%. At five years the corresponding figures were 88% and 91%. Sub group analyses in terms of age, ejection fraction and extent of vessel disease failed to show any significant differences between those randomised to medicine or surgery. A positive exercise test early after infarction does help to delineate those more likely to require intervention, but a negative exercise test is not an indication for complacency. PMID- 1290732 TI - A critical appraisal of in-patient neurological services in a subregional centre. AB - A computer database was established for the medical audit of admissions to the North Manchester General Hospital neurology unit. Over a six-month period, 277 patients completed 300 hospital stays. A higher proportion of patients were admitted from the North Manchester District compared with the peripheral districts served by the unit, suggesting that more neurology in these areas was performed by general physicians. This supports claims for an increase in the number of neurologists to improve the quality of service at district level. The introduction of a programmed investigation unit, closed at weekends, would allow financial savings since 60% of cases did not require a bed at the weekend. It would also allow more efficient pre-booking of investigations. The diagnostic yields from routine B12 and folate levels, syphilis serology, thyroid function tests, chest radiography and electrocardiography were low and should be replaced by more selective investigations. Savings might also be made by performing the 38% of myelograms restricted to the lumbar region in the out-patient department. The introduction of out-patient magnetic resonance imaging will make significant savings by obviating the need for many of the inpatient myelograms which were required in 55 patients. The simple and relatively inexpensive technology used in this study provided medical staff with valuable information on which to base changes in practice and evaluate their consequences. PMID- 1290733 TI - Randomised cross-over comparison of five inhaler systems for bronchodilator therapy. AB - The pharmacological efficacy of beta-2 agonists such as bronchodilators is well established, yet many patients fail to obtain optimum benefit from conventional metered-dose inhalers. This is usually because of difficulty in achieving adequate co-ordination between activation of the aerosol and inhalation. To some extent this problem can be alleviated by detailed personal instruction and re instruction, but the medical or paramedical staff needed to do this may be unavailable and in any case their time is expensive. To increase the benefit obtained from bronchodilators, therefore, pharmaceutical companies have produced a variety of devices, eg, large-volume (750 ml) spacers (Nebuhaler, Volumatic) which enclose a cloud of aerosol, obviating the need for actuation-inhalation co ordination, and breath actuated dry-power inhalers with (Rotahaler, Diskhaler) or without (Turbohaler) carrier powders. Subsequent compliance with treatment is dependent upon the acceptability of the inhaler device to the patient. PMID- 1290735 TI - Genital herpes: audit of cases referred by general practitioners to a department of genito-urinary medicine. AB - An audit was carried out of all cases of genital herpes referred by a general practitioner to a department of genito-urinary medicine from 1987-1990. Attention was paid as to whether or not the diagnosis had been made correctly and what drugs, if any, the patient had been prescribed. A total of 196 patients (78 men, 118 women) were eligible for study. GPs correctly diagnosed herpes in 32/78 (41%) of the men. Among the 46 who were not diagnosed, 12 were prescribed antibacterial drugs, three were prescribed antifungal cream, two were prescribed a combination of the above and three received miscellaneous non-antiviral agents. GPs correctly diagnosed 56/118 (47%) of the women. Sixty-two women were not diagnosed, of whom 17 were prescribed anti-bacterial drugs, 21 were prescribed antifungal cream, seven were prescribed a combination of these and six received miscellaneous non antiviral agents. GPs appeared to have difficulty in diagnosing genital herpes in these patients, with the result of prescription of inappropriate and expensive medications. PMID- 1290734 TI - Razoxane for Crohn's colitis and non-specific proctitis. AB - Oral razoxane 125 mg daily brought active Crohn's disease into remission when used alone and mainly on an out-patient basis in all nine patients studied. Remissions took several months to achieve, but no relapses have occurred on treatment and no surgery has been necessary in any of the patients. In the two patients with active non-specific proctitis, oral razoxane 125 mg daily rapidly controlled the condition. Apart from mild bone marrow toxicity in one patient, no other acute toxicity has occurred and no long-term side-effects have been observed. PMID- 1290736 TI - The aetiology and pathogenesis of vaginal candidosis: an update. AB - The aetiology and pathogenesis of the condition of vaginal candidosis is discussed in brief. The causative organism, the incidence and source of infection and various host and pathogen factors related to the disease state are dealt with. An update of current work relating to the cause of the recurrent condition is presented. PMID- 1290738 TI - The incompetent cervix--a review. AB - Repeated midtrimester pregnancy loss due to incompetence of the cervical os has long been recognised as a treatable condition, but the aetiology, diagnosis and management of this condition remain controversial. Some women have clinically obvious cervical incompetence and may benefit from a cerclage operation, but criteria for early diagnosis are not universally agreed upon. Universal agreement on the aetiology and diagnostic criteria is a prerequisite for determining which women may benefit from surgical management. PMID- 1290737 TI - The treatment of acute and chronic vaginal candidosis. PMID- 1290739 TI - Infarction of the tongue in Wegener's granulomatosis. AB - Wegener's granulomatosis is a form of systemic vasculitis. Untreated, it has a 90% two year mortality, but complete remission can be obtained in 93% of patients following treatment with cyclophosphamide (usually in combination with steroids). There is early and major involvement of the respiratory tract. Renal involvement adversely affects prognosis. PMID- 1290740 TI - Wolff-Parkinson-White syndrome mimicking myocardial infarction on ECG- exploitation by a heroin addict. AB - Wolff-Parkinson-White (WPW) syndrome produces several electrocardiographic features, including mimicking the changes of myocardial infarction. A case is described of an astonishingly well-informed heroin addict, who himself had WPW syndrome and who exploited his condition attempting to obtain opiates from hospital. PMID- 1290741 TI - Covert toxocariasis--a cause of recurrent abdominal pain in childhood. AB - Toxocariasis, usually caused by Toxocara canis, is a zoonosis acquired by ingestion of worms which inhabit the gut of young canines. Domestic pets, such as dogs, become infected from soil in public parks and playgrounds which are often heavily contaminated. Although toxocariasis is often regarded as having two principal, though uncommon, manifestations--visceral larva migrans (VLM) and ocular toxocariasis (OT)--recent studies have suggested otherwise. A third, more common, condition, termed 'covert toxocariasis', describes patients in whom positive toxocara serology is associated with a number of systemic and localised symptoms and signs (notably abdominal pain) but not VLM or OT. A quarter of patients with covert toxocariasis have no eosinophilia and, although symptoms regress after treatment, they may persist for months or years. We report a 13 year-old girl with recurrent abdominal pain who, despite positive toxocara serology, was extensively investigated for other abdominal pathology. PMID- 1290742 TI - Intrahepatic bilomas--a possible complication of cholecystectomy? AB - Biloma(s) were initially defined as encapsulated extrahepatic collection(s) of bile. Subsequently the definition was expanded to include abnormal intrahepatic bile collection(s) located outside bile ducts. Most descriptions are of subhepatic or subphrenic collections (extrahepatic bilomas), following surgical procedures involving the biliary system or trauma. We report a case of intrahepatic collections of very large amounts of bile, apparently following cholecystectomy. PMID- 1290744 TI - Sterno-costo-clavicular hyperostosis. AB - Sterno-costo-clavicular hyperostosis (SCCH) is a condition of unknown aetiology in which a chronic inflammatory osteitis affects predominantly the medical clavicle, sternum and distal tibia and femur, sometimes associated with skin disease. We report on two patients with the typical bony lesions of SCCH and no associated skin disease. PMID- 1290743 TI - Splenic abscess: is conservation applicable? AB - A rare occurrence of salmonella abscess in a congenital cyst of the spleen is presented. Although splenectomy was curative, the role of splenic salvage is discussed. Percutaneous drainage is curative in about 70% of cases and may be the treatment of choice in solitary thick-walled abscesses. It should be remembered, however, that residual or regenerated splenic tissue is no absolute guarantee against sepsis. The treatment of splenic abscess should be individualised. PMID- 1290745 TI - Severe orthostatic hypotension in carcinoma of the pancreas. AB - Autonomic dysfunction has been described in patients with advanced forms of cancer. We report a case of severe orthostatic hypotension in a patient with carcinoma of the pancreas in whom there was no clinical evidence of autonomic failure to account for the severity of the hypotension. Despite normal circulating levels of nor-adrenalin and an appropriate rise in the erect position, the vascular system appeared unresponsive. We suggest that in this patient the orthostatic hypotension was due to a paraneoplastic complication of the pancreatic tumour. PMID- 1290747 TI - Linkage between T cell receptor genes and susceptibility to multiple sclerosis: a complex issue. AB - Susceptibility to Multiple Sclerosis (MS) and to other autoimmune diseases has been linked to genes encoded within the HLA complex. More recent evidence indicates linkage between MS and genes encoded within or closely linked to the T cell receptor (TCR) beta chain gene complex. However, not all available data are concordant. Discrepancies are most likely rooted in the complex nature of TCR and MHC genes and interactions of their products in initiating and sustaining autoimmune responses. An evaluation of linkage of TCR and MHC genes to autoimmune disease processes must take into account the nature of polymorphism in the gene complexes, the complexity of autoimmune diseases along with the multigenic nature of genetic predisposition. These factors create a situation in which simple genetic linkage may be the exception rather than the rule. The present report reviews data concerning TCR and MS linkage and enumerates the complexities that arise in evaluating results from such studies. PMID- 1290746 TI - Antigen presenting cells and the immunogenetics of autoimmune diabetes in NOD mice. AB - Genetically-controlled defects in the development and function of antigen presenting cells may explain why NOD mice exhibit an impaired ability to induce tolerance and/or activate immunoregulatory T cells. These defects provide understanding for why diabetogenesis in NOD mice is so sensitive to immunomodulatory changes mediated through the environment. Although the unique MHC haplotype of NOD mice is clearly a major contributor to diabetes susceptibility, evidence for a complex interaction between MHC loci and many other polygenetic factors is reviewed. PMID- 1290749 TI - Genetic variability in tumor necrosis factor production: relevance to predisposition to autoimmune disease. AB - Rather than being involved merely in the effector arm of inflammatory processes that contribute to autoimmune organ destruction, a primary involvement of TNF may be in some of the more basic mechanisms that occur in autoimmune disease. In this review, data are presented on TNF-alpha that suggest the involvement of this cytokine in the genetic predisposition to autoimmune diseases such as lupus nephritis. PMID- 1290748 TI - The immunogenetics of susceptibility and resistance to murine experimental allergic orchitis. AB - The results of both clinical and experimental studies suggest that immunologic mechanisms may be significant in the pathogenesis of idiopathic infertility. We have defined and preliminarily characterized a number of immunoregulatory genes which control the phenotypic expression of infertility associated with autoimmune disease of the testis. Our studies utilizing the murine model of experimental allergic orchitis have clearly demonstrated that both classical (class II antigens) and nonclassical major histocompatibility complex-linked immune response genes play a central role in controlling disease susceptibility. We have mapped one nonclassical immune response gene, orchitis susceptibility gene-1 (Orch-1), to an interval of ca. 100 kilobases within the H-2S-H-2D region. In addition, immunogenetic analyses have identified two immune suppression genes, Orch-2 and Orch-3, which control active immunoregulatory mechanisms governing the phenotypic expression of disease resistance. The genetic control of autoimmune infertility in this model therefore appears to be polygenic. PMID- 1290750 TI - Immunogenetic aspects of clinical and experimental uveitis. AB - Genetic association of some immune-mediated human uveitic diseases with histocompatibility antigens, ethnic origin, familial background, or gender have suggested the presence a hereditary component in susceptibility. Experimental autoimmune uveoretinitis (EAU) can be induced in inbred rodents by immunization with evolutionarily conserved retinal proteins, and mimics many features of human uveitis. Susceptibility to EAU is genetically controlled, and the model is being used to study mechanisms that might affect susceptibility to ocular autoimmune disease. EAU expression in mice and in rats requires the presence of both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility in H-2k mice was tentatively mapped to the I-A subregion (HLA-DR equivalent), implicating epitope recognition as a major mechanism in susceptibility. In contrast, expression of the I-Ek gene product (HLA-DQ equivalent) appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include regulation of responses to lymphokines, hypothalamic-adrenal-pituitary axis hormones, mast cell/vascular effects, and possibly the T cell repertoire. The data are interpreted to suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background. These results might help to explain why only a minority of individuals with a susceptible HLA type develop uveitis, as well as the variable incidence of disease in HLA-identical populations of different ethnic backgrounds. PMID- 1290752 TI - 22 ways to improve the service in your pediatric dental office. PMID- 1290751 TI - Genetic factors in demyelinating diseases: genes that control demyelination due to experimental allergic encephalomyelitis (EAE) and Theiler's murine encephalitis virus. PMID- 1290753 TI - A clinical evaluation of root resorption by formocresol treatment in 120 cases of pulpotomy in permanent molars. AB - The effect of a formocresol pulpotomy of a 120 permanent molar showed external and internal resorption on distal root in lower molar, and palatal root in the upper molar. In this study 33.3% were male and 66.7% were female. The age distribution of patients was 16 to 20 years of age and 21 to 25 years of age. The rate of resorption for chronic pulpitis was more than acute pulpitis. The success of formocresol pulpotomy treatment at the end of the 10th year for acute pulpitis was 92.26% in contrast to 84% for chronic pulpitis. PMID- 1290754 TI - The prevalence of congenitally missing teeth in class I, II, III malocclusions. AB - A total of 1619 patients, 502 males and 1117 females, ranging in age from 6.5 to 32 years old were examined. The study used a full set of radiographs, panographs, lateral cephalogram and study models to find the highest prevalence of congenitally missing teeth in class II malocclusion patients and a significant amount of missing maxillary teeth in Class III malocclusion patients. PMID- 1290755 TI - The effect of inferior alveolar neurotomy on mandibular growth in the rat. AB - To assess the role of possible growth alterations on the mandible, an investigation was undertaken to analyze the effect of bilateral sectioning the inferior alveolar nerve on mandibular growth in 21 day-old Charles River strain rats. The experimental group (n = 26) was subjected to bilateral resection of the inferior alveolar nerve, while 34 animals of comparative age were sham operated and served as controls. At 111 days maturity, the following alterations in the size and shape of the mandible were observed in the experimental animals: 1) the coronoid process in the experimental group was longer, slightly thinner and more curved, 2) antegonial notching was more pronounced. Mandibular length increased from 14 mm to 20.9 mm in control animals, while in the experimental animals, the length of the mandible was 19.6 mm. Thus, the length of the mandible in experimental group was 1.3 mm on the average shorter than the control group (p < 0.0001) and the difference between the two groups was highly statistically significant. The average 1.6 mm difference between the mandibular height of control and experimental animals indicated that the experimental mandibular ramus was approximately 0.5 mm shorter than in control animals. The difference in ramus height between the groups was statistically significant (p < 0.003), but the difference in intercondylar width between control and experimental groups (p < 0.31) was not statistically significant. The corpus height between control and experimental groups was statistically significant (p < 0.0001). Incisor overjet increased from 1.3 mm in control group to 3.2 mm in experimental group (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290756 TI - Resin adhesion to the ground primary enamel: influence of etching times and thermal cycling test. AB - The purpose of this study was to investigate the influence of etching times and thermal cycling on resin adhesion on ground primary enamel. Two hundred bovine mandibular primary incisors were used. Materials used in this study were 40% phospholic acid gel, Photo Bond and Photo Clearfil A (Kuraray Co., Kurashiki, Japan) in PCA groups and 37% phospholic acid gel, Scotch Bond and Silux (3M Co., St. Paul, MN) in the Silux groups. The etching times were 0, 10, 20, 30 and 60 seconds. Shear bond strengths were tested. After the shear bond strength test, the test surfaces of the enamel and the resin specimens were observed using the SEM. The etching times that showed the highest bond strengths were 30 seconds both in the PCA non-thermal cycled group (80.10 +/- 13.01 MPa) and the PCA thermal cycled group (78.99 +/- 10.93 MPa), 20 seconds in the Silux non-thermal cycled group (76.77 +/- 12.99 MPa) and 60 seconds in the Silux thermal cycled group (63.61 +/- 19.64 MPa). The influence of thermal cycling test to the enamel resin adhesion is relatively slight both in the PCA group and the Silux group. PMID- 1290757 TI - Clinical application of visible light-cured fluoride-releasing sealant to non etched enamel surface of partially erupted permanent molars. AB - A visible light-cured fluoride-releasing sealant was applied to non-etched enamel surfaces of partially erupted permanent molars. A scanning electron microscope was used to find an effective procedure to clean pits and fissures of the occlusal surfaces prior to application of the sealant. This procedure proved clinically acceptable and effective for prevention of dental caries immediately after eruption of permanent molars. PMID- 1290758 TI - Chronic disseminated histiocytosis X: a case report. AB - A case of chronic disseminated histiocytosis X (Hand-Schuller-Christian Disease) of the mandible is presented. Multi-modal approach to management is discussed. PMID- 1290759 TI - Prader-Willi syndrome: report of a case with special emphasis on oral problems. AB - A case with Prader-Willi syndrome (P.W.S.) is reported. The patient manifests: obesity, hypogonadism, hypotonia, mental retardation, small hands and feet, prominent forehead, bitemporal narrowing, strabismus, hypoplastic teeth, generalized caries and thick, sticky saliva. The patient is presented at two different ages (10 and 14), and the development of the characteristics of the syndrome is described. Emphasis is given to the oral findings especially to the generalized caries, that led to an almost complete destruction of the teeth. The role of the dentist is considered to be important for the control of the dental problem of this syndrome. PMID- 1290760 TI - Mirror image in aplasia of a premolar in a monochorial twin: Case report and review. PMID- 1290761 TI - Corporal punishment. PMID- 1290762 TI - Ethics and research on adolescents. PMID- 1290764 TI - Substance abuse among sexually abused adolescents and their families. AB - The concurrence of substance abuse and history of sexual abuse among adolescents has prompted this study of substance abuse patterns among families of adolescents who report incest or extrafamilial sexual abuse. A total of 3,179 ninth-grade students in a rural midwestern state completed a survey that included questions about individual and family substance abuse. Adolescents who had been sexually abused were more likely to report substance abuse for themselves as well as for members of their immediate families. They were also more likely to report that they used substances because of family problems, school problems, and because they were sad, lonely, or angry. Adolescents reporting a parent with an alcohol or a drug problem were more likely to use cigarettes, marijuana, alcohol, or "speed." Adolescents experiencing extrafamilial abuse reported more alcohol abuse and more alcohol-related problems than those who experienced incest. There were similar reports of parental and familial alcohol and drug problems among these experiencing incest and those experiencing extrafamilial abuse. Those with drug abusing parents, however, were most likely to report some kind of sexual abuse history. PMID- 1290763 TI - Predictors of condom use in sexually active adolescents. AB - Unprotected sexual intercourse places a substantial number of adolescents at risk for sexually transmitted disease (STD) and human immunodeficiency virus (HIV) infection. While the most effective means of preventing STD/HIV infection among sexually active adolescents is consistent condom use, little is known about the factors that influence their consistent use among adolescents. This study of adolescents (n = 1049, mean age = 16.2 years) found that of the 266 teens who recently became sexually active, only 29% reported using condoms consistently. Consistent condom use was more frequent in males, those with little history of risk behavior and those with stronger intentions to use condoms in the future. Fear and anxiety of HIV, attitudes about risks other than HIV, and other safe behavior intentions were not significantly related to consistent condom use. Although intentions and recent behavior were significantly related, a different group of factors was found to predict intention to use condoms (e.g., perception of condom use by friends, general impulsive attitudes). Identifying and understanding the factors that influence adolescent sexual behavior and intentions is important for developing maximally effective HIV education/prevention programs. PMID- 1290765 TI - A descriptive study of trauma, alcohol, and alcoholism in young adults. AB - Young adults, 18-20 years of age, admitted to a trauma center via the emergency department, were studied to determine if they had been drinking prior to their injury event. The prevalence of self-reported chronic alcohol problems was examined using the short Michigan Alcohol Screening Test (SMAST). Of the 319 subjects, 131 (41%) tested positive for alcohol, including about one-half of those with intentional injuries and 38% with unintentional injuries. Approximately 22% had blood alcohol concentrations of 100 mg/dL or more, indicating they were legally intoxicated at the time of their injury. Of study subjects who completed the SMAST, 49% attained scores suggesting potential or probable alcoholism, and 20% had already sought some type of treatment, despite their young age. Health-care practices and policies related to these findings include routine screening of trauma patients for alcohol abuse and integration of chemical dependency intervention services with trauma care. PMID- 1290766 TI - Patterns of teen exposure to a community-based violence prevention project. AB - This paper describes the implementation of a community-based youth violence prevention project that utilized an educational curriculum and a mass media campaign. The extent of penetration of the intervention into target areas and the degree of contamination of control areas are assessed, and the most frequently contacted forms of educational outreach are identified. Two sources of data, provider interviews and a random digit dialed telephone survey, were used to track the source and extent of teens' exposure to the intervention. Agency provider data revealed that 40% of the 92 contacted agencies actually conducted violence prevention education, reaching 22% of the target area teens. Approximately one-half of the surveyed teens reported some exposure to the program, with 13% of the teens in target areas reporting participation in interactive educational activities associated with the project. The most common source of exposure was the media campaign. Most teens report a single exposure, usually to the media campaign, although 29% report contact with more than one form of violence prevention education. While the project did not achieve community saturation, the data show that the community-based model of intervention for violence prevention is feasible and effective in reaching teenagers. This research highlights some difficulties in evaluating prevention programs, including reconciling community ownership with project identification, the ethics of curtailing services for control purposes, and factors influencing recall of participation. PMID- 1290767 TI - Psychosocial and economic factors associated with infant feeding intentions of adolescent mothers. AB - The infant feeding intentions of 64 primiparous, adolescent females, ages 14-18 years, were studied to assess factors which differentiated those who chose breastfeeding from those who did not. The study population consisted of 43 Hispanic, 9 black, 7 non-Hispanic white, and 5 Filipino or Southeast Asian subjects interviewed after delivery. Among the Hispanics, 31 primarily spoke Spanish, and 12 primarily spoke English. A total of 72% intended to breastfeed, and 22% planned to exclusively formula feed. Those teens who intended to breastfeed were significantly older, more often married, more likely to be Hispanic and Spanish speaking, and less likely to have been in school during the pregnancy. In addition, teens were more likely to choose breastfeeding if they had been breastfed themselves or exposed to other women who breastfed. These data suggest that the younger, non-Hispanic, single teen who is enrolled in school and lacking exposure to breastfeeding is the most in need of breastfeeding-promotion programs. PMID- 1290768 TI - Transition program from pediatric to adult care for cystic fibrosis patients. AB - A survey of adolescents and young adults with cystic fibrosis (CF) attending an adult CF center was conducted to evaluate a transition program as a means of transferring care from pediatric to adult setting. A total of 40 patients completed a self-administered questionnaire of whom 13 (32.5%) went through the transition program, and 21 (52.5%) received their care at the University of Michigan Cystic Fibrosis Center. Fourteen patients (35.0%) were cared for at other pediatric CF centers, and five (12.5%) were first diagnosed as adults. All those in the transition program approved of having the visit with the internal medicine physician in the pediatric clinic. Most thought that the transition program made the change from pediatric to adult care easier. All patients were comfortable leaving the pediatric clinic after the transition period. Of the 40 patients, 17 (42%) recommended that other patients go through the transition program, although 9 of these 17 patients did not themselves go through the transition program. Twenty-six patients (65%) preferred the adult program. These findings suggest that adolescents with CF should be encouraged to transfer their medical care to an adult CF Center once they have reached an agreed-upon age. This process should be smooth and should occur as part of the regular CF care. This is possible through a well-structured and well-organized transition program with committed pediatric and adult staff. PMID- 1290769 TI - Labeling relaxation procedures: impact on adolescent's self-report of effectiveness. AB - Adolescents are being taught relaxation techniques by health-care professionals with increased frequency. The present study examined the effect, on self-reported relaxation, of labeling passive relaxation techniques as "hypnotic relaxation" or as "relaxation training." Subjects were 64 adolescent college students who scored above the 50th percentile, from a subject pool of 189 potential subjects, on the Spielberger Trait Anxiety Inventory. A two by two by two factorial design was utilized with sex, label (hypnotic relaxation versus relaxation training) and relaxation technique (hypnotic induction versus autogenic training) as the independent variables. Under the guise of an investigation of the physiologic correlates of relaxation, subjects were assigned at random to one of four groups. Manipulations of label and relaxation technique were presented on tape via an intercom system. The dependent variable, perceived degree of relaxation, was obtained using a form presented as a "double check" of the accuracy of the physiologic monitoring equipment to which subjects seemingly were attached. Results indicate that the label attached to relaxation techniques can have a significant effect on an individual's subjective report of relaxation depending on the subject's sex. PMID- 1290770 TI - Laparoscopic cholecystectomy in teenagers. AB - The positive experience with laparoscopic cholecystectomy (LC) in the adult surgical community encouraged us to perform LC in our last nine adolescent patients requiring cholecystectomy. There were no operative or postoperative complications, and the average hospital stay was less than 3 days. All the teenagers resumed their normal activities 1 week after surgery and were pleased with the small operative scars. Once the technique has been mastered and adequate experience gained with the new instrumentation, laparoscopic cholecystectomy would seem to offer many advantages in the teenage patient. PMID- 1290771 TI - Health profile of pregnant adolescents among selected tribal populations in Rajasthan, India. AB - Among primitive tribal communities in India, girls are traditionally married immediately after attaining menarche. In the present study all adolescent girls in the second and third trimesters of pregnancy from 15 randomly selected villages of 4 tribal development blocks of Udaipur district (South Rajasthan State, India) were studied. The data were analyzed with reference to parity, anthropometry, anemia, and other dietary deficiencies. A total of 54 adolescent girls (13-19 years of age) were included in the present study. Of these, 59% (n = 32) were found to be primigravidas, 30% (n = 20) were pregnant for the second time, and 2 girls were pregnant for the third time. A majority were illiterate (n = 46), and almost all of them were found to be suffering from moderate-to-severe anaemia (n = 51). Similarly, a large majority (n = 46) had a body mass index (BMI) less than normal and body weight less than 42 kg. Two of the pregnant girls were also found to be suffering from pellagra, while approximately one-third of the girls had vitamin A deficiency. Only 2 had ever practiced family planning, consisting of some herbal preparations given to them by the folk doctor. Of the study participants, 19 girls (35.0%) were in the third trimester of pregnancy; of these, 7 had evidence of malpresentation or cephalopelvic disproportion. This study highlights the health profile and needs of pregnant adolescents among tribal populations in a drought-affected area in India. PMID- 1290773 TI - Asthma prevalence and management in Australian adolescents: results from three community surveys. AB - Three population surveys of asthma, conducted as part of a community-based asthma education program in southwestern Sydney, Australia, illustrate the relationship between health behaviors and asthma morbidity. The first survey was carried out in five secondary schools (n = 2514, 52% participation rate); the second survey, in eight schools (n = 4550, 82% participation rate); and, the third survey was conducted among patients who attended 38 general practices in the region (n = 633 adolescents, 72% participation rate). The prevalence of diagnosed asthma in Australian adolescents across all three studies was 16.5% (95% CI, 15.7%-17.3%). Asthma prevalence declined in males, but increased in females from ages 12-15 years. It was noted that smoking prevalence was similar in asthmatic adolescents, compared with nonasthmatics, and that the adoption of smoking occurred at similar ages. Further, behavioral self-management of asthma was infrequent in this group, with low levels of preventive practice and preventive medication use. We present a conceptual model of the barriers to optimal asthma management among asthmatic adolescents. The results of these surveys have led to community-wide efforts to improve asthma management and decrease smoking prevalence among these adolescents. PMID- 1290772 TI - Pregnant again? Psychosocial predictors of short-interval repeat pregnancy among adolescent mothers in Mexico City. AB - Which adolescent mothers are most likely to become pregnant soon after their first delivery? This study identifies and explores selected background, pregnancy, and postpartum predictors of short-interval repeat pregnancy among urban Mexican adolescents who were single when they conceived their first pregnancy. Of 137 adolescents followed until their second postpartum year, 26 had short-interval repeat pregnancies. These pregnancies were most likely to occur if the teenager was married or in consensual union by 5 months postpartum, was not using an IUD, and had a mother who had been an adolescent mother. Being married or in consensual union postpartum was, in turn, predicted by positive reactions of the adolescent and her partner during the first pregnancy. Nonuse of IUD was more likely if the adolescent had left school prior to pregnancy, did not receive support from her partner during the first pregnancy, and had not obtained an IUD before hospital discharge after first delivery. Adolescents whose mothers had been teen mothers came from more disadvantaged families. PMID- 1290775 TI - Health and health needs of homeless and runaway youth. A position paper of the Society for Adolescent Medicine. PMID- 1290774 TI - Pulmonary embolus in an adolescent on oral contraceptives. AB - Deep venous thrombosis with pulmonary embolus is a rare complication of oral contraceptives, which generally occurs in adult women and becomes more common with increasing age. These complications are believed to be less common with low dose oral contraceptives than with the higher dose forms. This is a case report of a deep venous thrombosis presenting with a life-threatening pulmonary embolus in an adolescent on low dose triphasic oral contraceptives. PMID- 1290776 TI - How can CRNAs receive third party reimbursement as recognized providers of anesthesia service? AB - To remain professionally viable, CRNAs must receive fair and adequate reimbursement for services rendered. Denial of payment by third party insurers can result in frustration, loss of income, and potential negative impact on the right to practice. The insurance industry and other health care organizations categorically and conditionally deny reimbursement for a variety of reasons. Categorical denial is the greatest threat to practice. Conditional denial can usually be resolved. When discussing issues with insurers it is important to deal with those in a position to make or influence policy. It is important for individuals and their respective state associations to be familiar with pertinent insurance laws and regulations because they identify practitioner rights and claims that can be made against the insurer. Any categorical denial should be brought to the state association's attention and investigated for possible illegal action. PMID- 1290777 TI - Comparison of low-dose sufentanil and fentanyl in balanced intravenous anesthesia for orthotopic cardiac transplantation. AB - A retrospective review was made of the records of 118 patients who received orthotopic heart transplant. Anesthetic techniques, drugs, dosage, hemodynamic profiles, intubation time, and intensive care unit stay were evaluated. The efficacy of sufentanil was compared to fentanyl in a balanced anesthetic when given in lower doses. Patients were given adequate anesthesia with total opioid doses of sufentanil, 6.5 +/- 2.9 micrograms.kg-1, or fentanyl, 58.9 +/- 24.9 micrograms.kg-1. Midazolam was used in all patients (mean dose 7.6 +/- 3.8 mg). There were no differences between the groups in complications, requirements for inotropic support, or time to extubation. A significantly higher pulmonary artery pressure was noted in patients who received sufentanil, but not fentanyl, pretransplant. The pulmonary artery pressures were not significantly elevated posttransplant. This review indicated that patients can be safely anesthetized with either combination of drug in lower doses than previously recommended. PMID- 1290778 TI - Association of coagulation tests with blood use during liver transplantation. AB - This study is a retrospective review of 263 adult patients who underwent either their first or their second orthotopic liver transplantation between March 1985 and January 1992. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were analyzed for correlation with the amount of blood transfused 70 minutes after reperfusion. The data were analyzed to estimate correlation between variables using Spearman's rank correlation coefficient. A P value less than .05 was considered significant. Data analysis demonstrated a positive association between APTT and blood transfusion in all disease states, with the exception of patients who had retransplantation. A positive association existed between PT and the amount of blood transfused in patients with alcoholic liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis. PMID- 1290780 TI - Publish your thesis as an article or a book. PMID- 1290779 TI - Mivacurium chloride. AB - This brief review summarizes the major research to date involving the clinical use of mivacurium in adults and children. The principle focal points are the pharmacokinetic and pharmacodynamic characteristics of the drug and the side effects that have been commonly observed with its clinical use. Comparisons and contrasts with vecuronium, atracurium, and succinylcholine are made. Particular attention is focused on dosages, infusion rates, recovery characteristics, and individual patient variability. PMID- 1290781 TI - Craniofacial applications for the Medpor porous polyethylene flexblock implant. AB - We describe use of flexblock, a newly designed Medpor porous polyethylene implant. This implant is ideally suited for repair of small to medium-sized cranial defects and correction of contour deformities. Medpor is used for a wide variety of maxillofacial procedures, and its properties make it an excellent choice for the cranium. It is a highly stable and somewhat flexible porous alloplast that has been shown to exhibit rapid soft-tissue and bone ingrowth. Flexblock, which was designed as an onlay for calvarial bone graft donor sites, has a smooth exterior surface and a series of conical ridges on its undersurface that enable easy bending, good contour adaptability, and suitable strength. We used the Medpor flexblock implant in 12 patients over 2 years for correction of contour deformities, cranial defects, and reconstruction of the supraorbital rim. There were no complications. Larger cranial defects and complex reconstructions can be performed using customized Medpor implants. The properties of Medpor and the flexblock design make this implant an excellent alternative to the existing methods of cranioplasty and cranial contour correction. PMID- 1290783 TI - Reconstruction of a large congenital cranioorbital defect with a species-specific demineralized bone implant. AB - Bone grafting is one of the most common operative procedures in craniofacial surgery today. Almost all surgical defects have to be closed with a graft, and all stabilized segments require bone grafts for stabilization prior to fixation. In certain circumstances, however, lack of availability of large grafts necessitates the use of bone substitutes. In the patient presented, a large defect--which is larger than a critical size defect--did not close on its own, even though neonates have a very high potential for forming bone around the dura. The defect was closed with demineralized bone implantation and showed complete filling of the defect through the bone induction principle. PMID- 1290782 TI - Solitary calvarial plasmacytoma. AB - One patient with a solitary plasmacytoma of the frontal bone was treated with complete surgical resection. To reconstruct the large calvarial defect, a split thickness calvarial graft was harvested from the parietal area and secured in place with miniplates. Solitary plasmacytomas of the calvaria are not common. Clinical presentation, diagnostic criteria, therapeutic approaches, and prognosis are discussed. PMID- 1290784 TI - Demineralized perforated bone implants in craniofacial surgery. AB - Between July 1990 and September 1991, demineralized perforated allogeneic bone implants (Pacific Coast Tissue Bank, Los Angeles, CA) were placed in 72 patients. Because many patients received more than one implant, a total of 248 implants were used in 80 procedures. The technology of processing demineralized bone implants is described in detail. All patients were operated on by one surgeon (K.E.S.) at the Humana Craniofacial Institute in Dallas, Texas. Forty-one patients had craniofacial deformities, 16 had secondary deformities following cleft lip and palate repair, 8 had bony defects following removal of tumors, and 10 had various skeletal deformities following trauma. Of the 72 patients, 6 had two surgical procedures during which additional implants were inserted. Implants placed in the cranial vault and the maxillary complex, including alveolar grafts, were inlay grafts, whereas implants placed in the orbital, nasal, paranasal, temporal, and malar areas were onlay grafts used for contouring, augmentation, or both. Complications were limited to delayed wound healing in 6 patients. According to our observations, demineralized perforated bone implants represent an encouraging alternative to autogenous bone grafting. Further clinical and experimental studies are necessary to obtain more information about this material. PMID- 1290785 TI - Demineralized bone matrix polydioxanone composite as a substitute for bone graft: a comparative study in rats. AB - Demineralized bone matrix (DBM) has been successfully used as a substitute for bone grafting. Autogenous bone grafts (ABG) may cause donor site morbidity and undergo significant resorption. DBM may overcome these problems but is mechanically unstable when originally placed. We explored using a slowly resorbable template, polydioxanone (PDS), in combination with DBM and compared it to ABG in a rat 9 x 9 mm cranial defect model. After both 1 and 3 months, histologically and biochemically well-formed bone was present in ABG/PDS and DBM/PDS-treated defects, but not in control defects (PDS alone). Mechanical push out tests using a servohydraulic testing frame were conducted. Maximum load before failure of DBM/PDS increased from 65% at 1 month to 100% of that of intact skull at 3 months. In contrast, ABG/PDS was 50% as strong as DBM/PDS and not significantly stronger than PDS alone. ABG/DBM did not significantly increase in strength from 1 to 3 months. We conclude that DBM/PDS is better than ABG/PDS in treating cranial defects in the rat model, and that an absorbable osteoinductive bone substitute with superior mechanical advantage is possible without the disadvantages of ABG. PMID- 1290786 TI - An in utero model of craniosynostosis. AB - To define better the pathophysiology of craniosynostosis, we developed an in utero model in rabbits. Premature fusion of the sutures was achieved by osteoinduction using demineralized bone matrix (DBM). Thirty-six fetuses from 18 time-dated pregnant rabbits underwent coronal strip craniectomies and implantation of DBM at 25 days of gestation (term = 31 days). Seventeen (47%) survived vaginal delivery and 10 (28%) survived for long-term follow-up. Surviving, operated animals demonstrated bony fusion across the coronal sutures presumably due to osteoinduction by the DBM. Coronal computed tomographic scans with sagittal reconstructions revealed that experimental animals had taller and wider skulls than nonoperated control animals. We conclude that employing DBM to create craniosynostosis in the fetal rabbit is technically feasible. Such a model may be used to more clearly define the pathophysiology of craniosynostosis and to evaluate methods of treatment. PMID- 1290787 TI - Bending mechanics of bone grafts: an experimental study. AB - We compare the mechanical properties of rib and cranial grafts subjected to bending stresses and analyze the modification of those properties following miniplate fixation. Standardized side-paired rib and cranial bone samples were harvested from human cadavers. Twenty bone specimens were divided into four study groups, comprising rib and cranial grafts, with and without miniplate reinforcement. Bone segments were subjected to measured stresses in an Instrom unit with simultaneous strain recording. The stress/strain curves were analyzed to determine the modulus of elasticity, failure points, and elastic properties. Experimental findings and clinical implications are discussed. PMID- 1290788 TI - Trigonocephaly. AB - Trigonocephaly has been described either as an isolated anomaly or as part of the clinical spectrum of some well-known syndromes. Treatment, complications, and prognosis are closely related to the manifestations of the associated anomalies. We report on the main types of syndromes with trigonocephaly and the management of this condition. PMID- 1290789 TI - Lower-third facial injuries: management and complications. AB - I report 1,110 patients with lower-third facial injuries isolated from 1,608 patients with different types of facial injuries. Mixed injuries (bone and soft tissue) were most common (72%; n = 805). The most common site of fracture was the body of the mandible (26.12%; n = 290). One hundred sixty-three patients underwent soft-tissue and bony reconstruction with a local soft-tissue flap or an iliac bone graft, or both. Three procedures failed because of gingival tearing. Other treatments ranged from conservative treatment to different types of closed or open reduction. Postinjury and postsurgery complications were many and involved soft tissue, nerves, tongue, and bones. The follow-up period ranged from 3 months to 3 years. PMID- 1290790 TI - Fixture design and overload influence marginal bone loss and fixture success in the Branemark system. AB - It has been documented that the long-term clinical outcome of the Branemark system is very favourable. However, failures do occur before and after loading. This study examined the differences in marginal bone loss between standard and self-tapping fixtures and attempted to explain excessive marginal bone loss or loss of osseointegration during the first 3 years of loading. Marginal bone loss (scored on long cone radiographs) and fixture failure rate were compared for different fixture designs. For standard fixtures, in comparison with self-tapping fixtures, the failure rate was clearly higher before as well as after loading. However, for successful fixtures no difference in marginal bone loss was observed. For the conical fixtures an increased marginal bone loss around the smooth part was observed. The effect of fixture overload, marginal bone height and loss of osseointegration was examined in 69 patients with 1 and 15 patients with 2 fixed full prostheses, and in 9 patients with an overdenture in the upper jaw. Excessive marginal bone loss (more than 1 mm) after the first year of loading and/or fixture loss correlated well with the presence of overload due to a lack of anterior contact, the presence of parafunctional activity and osseointegrated full fixed prostheses in both jaws. PMID- 1290791 TI - Putative periodontal pathogens on titanium implants and teeth in experimental gingivitis and periodontitis in beagle dogs. AB - The microflora around titanium implants and teeth in 4 beagle dogs was analyzed in order to follow the longitudinal development from healthy conditions to experimental gingivitis and periodontitis. A 2-month plaque control program was performed to establish healthy conditions on titanium implants and control teeth (baseline, day 0). Subgingival bacterial samples and radiographs were obtained. The plaque control was ceased and all measurements were repeated on day 21 (gingivitis). A new period of plaque control was initiated to re-establish healthy conditions (day 49). A cotton ligature was placed subgingivally around the implants and the control teeth to induce tissue breakdown. The ligatures were removed on day 91. The study was completed with registrations on day 121 (periodontitis). No significant microbiological difference was found between titanium implants and teeth in healthy conditions and in gingivitis and periodontitis. The mean total viable count increased 10 times on implants as well as on teeth. Streptococci were dominating at baseline: 40.2% on implants and 60.6% on teeth and decreased in gingivitis to 11.7% and 5.4%. When periodontitis had developed, the proportion of streptococci was < 1%. At baseline few Porphyromonas gingivalis and Prevotella intermedia were detected. They increased at gingivitis to 37.4% and 21.0%; when periodontitis developed, they comprised about 25.0%. Microbial colonization and establishment on titanium implants with healthy gingiva, experimental gingivitis and periodontitis follow the same pattern as on teeth. PMID- 1290792 TI - Evaluation of different methods to clean titanium abutments. A scanning electron microscopic study. AB - The cleaning effectiveness of different treatment methods for titanium abutments was evaluated using scanning electron microscopy (SEM). In the mandible of 4 beagle dogs, 25 titanium abutments were installed (modum Branemark). After 16 weeks of plaque accumulation, mineralized deposits had formed on 23 abutments. Each of these abutments was subjected to one of the following treatment methods: scaling with (1) metal, (2) plastic, or (3) ultrasonic instruments; (4) air polishing, (5) weekly rubber cup polishing or (6) daily brushing with a conventional toothbrush. Fourteen abutments were removed immediately after treatment. On 9 abutments, the scaling procedures and air-polishing were repeated after another 16 weeks of plaque accumulation. The abutments were prepared for SEM, and each of them was viewed and photographed at 3 different magnifications. The photomicrographs were evaluated by 3 examiners who, guided by reference pictures, gave each abutment a "cleanliness" score, ranking from 0 to 5. Regular rubber cup polishing and regular brushing resulted in the highest surface cleanliness, while the air-polishing procedure showed the lowest cleanliness score. None of the 3 scaling methods created a cleanliness score better than 3. The 3 scaling methods were considered equal in their cleaning effectiveness. No differences could be observed between surfaces treated 1 x or 2 x. Taken the present findings and those of other studies concerning the effects of scaling on the surface roughness and biocompatibility into consideration, it was concluded that plastic scalers may be the instruments of choice for debridement of titanium implant surfaces. PMID- 1290793 TI - Mechanical resistance of cemented post and core buildups for ITI-Bonefit implants. AB - In order to improve the prosthetic versatility of the ITI-Bonefit implant system, a clinical technique was tested whereby a custom made post and core buildup was cemented into implants. Specially designed threaded and serrated posts were machined in precious metal. After the posts were seated into the threaded channel of the implants, cores were built using autopolymerizing resin. Those were then cast and cemented into the implants. For the remainder of the procedure, the buildups were treated like natural abutments using conventional prosthodontic techniques. Mechanical tests were performed to assess the clinical viability of these buildups. The ultimate tensile strength of annealed posts lies in the 700 800 N range. By comparison, the pull-out resistance of posts cemented into natural roots ranged between 108 and 177 N, and the maximum pull-out resistance of manufactured abutments is about 1040 N. When the resistance against lateral forces was tested, the cemented build-ups ranged between 981 and 1128 N, whereas natural teeth fractured between 206 and 903 N depending on the diameter of the root. Manufactured abutments failed at stress levels of about 1020 N. Considering these favorable results, we conclude that the technique described above can be applied clinically for further investigation. Additionally, we suggest some modifications in implant design that would enhance the versatility of the system. PMID- 1290794 TI - Healing-in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog. AB - The aim of these animal experiments was to characterize and evaluate the healing in of root analogue titanium implants fitting with high precision to the alveolar wall. Four beagle dogs were used in the study. The roots of the 3rd and 4th mandibular premolars in both quadrants of 3 dogs and in 1 quadrant of 1 dog (dog 4) were extracted after hemisection. Each root was machine-copied to 1 titanium analogue. In dog 4, however, 2 titanium analogues were fabricated from each of the 4 extracted roots. This enabled insertion of analogues also into the contralateral sockets obtained by extraction of the corresponding roots immediately before implant installation, which was undertaken 2 weeks after the first extractions. Thus, in all, 32 analogues were implanted in their respective (or contralateral) sockets following ridge incision and elevation of mucoperiosteal flaps. The analogues were carefully covered by the repositioned flaps. In dog 4, 2 analogues from the immediate sockets and 2 from the 2-week sockets were surgically exposed and supplied with titanium crowns after a healing period of 2 months. The healing after implantation was evaluated by clinical, radiographic and histological measures after 2, 12 or 36 months. Two analogues (6%) were lost due to early (during the 1st week) exposure to the oral cavity. Another 2 analogues (6%) were, although not exposed, encapsulated by soft tissue and were easily removed with a surgical forceps. Twenty-eight analogues (88%) were healed-in by contact between bone and implant (osseointegration).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290795 TI - Osseous healing of experimentally created defects in the calvaria of rabbits using guided bone regeneration. A pilot study. AB - The aim of this study was to test whether healing of extensive transosseous defects in the calvaria can successfully be achieved using guided bone regeneration. The results demonstrated complete osseous bridging of the skull defect in the test specimen. In the control specimen, fibrous connective tissue occupied the area of the skull defect. PMID- 1290796 TI - Long-standing plaque and gingivitis at implants and teeth in the dog. AB - The experiment was performed to evaluate the effects of long-standing plaque on the gingiva and peri-implant mucosa. 5 beagle dogs were used in the study. The mandibular right premolars were extracted. 3 months later, 3 titanium fixtures were installed and after another 3 months, abutment connection was performed. Plaque control, in the implant as well as the contralateral tooth regions, was maintained during a 4-month period prior to the start of the main experiment. On Day 0, the teeth and implant sections were examined with respect to plaque and gingivitis. The plaque control program was terminated. The animals were subsequently fed a diet which allowed gross plaque accumulation. After 90 days of undisturbed plaque formation, the dogs were re-examined and biopsies harvested from implants and contralateral teeth. On day 90, all teeth and implants had accumulated large amounts of plaque. The soft tissue at implants and teeth bled on gentle probing. The histological examination of the gingiva and the peri implant mucosa revealed: (i) both tissues contained an inflammatory cell infiltrate; ICT, (ii) the apical extension of ICT was more pronounced in the peri implant mucosa than in the gingiva and (iii) the composition of the 2 lesions had many features in common. PMID- 1290797 TI - Group sequential distribution-free methods for the analysis of multivariate observations. AB - Many studies involve the collection of multivariate observations, such as repeated measures, on two groups of subjects who are recruited over time, i.e., with staggered entry of subjects. Various marginal distribution-free multivariate methods have been proposed for the analyses of such multivariate observations where some measures may be missing at random. Using the multivariate U statistic of Wei and Johnson (1985, Biometrika 72, 359-364), we describe the group sequential analysis of such a study where the multivariate observations are observed sequentially--both within and among subjects. We describe a multivariate generalization of the Hodges and Lehmann (1963, Annals of Mathematical Statistics 34, 598-611) estimator of a location shift that can be obtained via the multivariate U statistic with the Mann-Whitney-Wilcoxon kernel. We then describe large-sample group sequential interval estimators and tests based on an aggregate estimate of the location shift combined over all of the repeated measures. We also describe how the same steps could be employed to perform a group sequential analysis based on any one of the variety of marginal multivariate methods that have been proposed. These methods are applied to a real-life example. PMID- 1290798 TI - Two-sample nonparametric estimation and confidence intervals under truncation. AB - We consider point estimates and confidence intervals for the difference in location or scale between two populations when the observations are subject to truncation. We suggest procedures analogous to those for the complete-sample case. A rigorous justification is presented to support the proposed confidence interval procedure. Finally, some simulations verify the properties of the estimators and confidence intervals. We illustrate the procedure using data on tumor size. PMID- 1290799 TI - Nonparametric estimation and testing in a cure model. AB - Nonparametric generalized maximum likelihood product limit point estimators and confidence intervals are given for a cure model with random censorship. One-, two , and K-sample likelihood ratio tests for inference on the cure rates are developed. In the two-sample case its power is compared to the power of several alternatives, including the log-rank and Gray and Tsiatis (1989, Biometrics 45, 899-904) tests. Implications for the use of the likelihood ratio test in a clinical trial designed to compare cure rates are discussed. PMID- 1290800 TI - Estimation of completeness and adjustment of age-specific and age-standardized incidence rates. AB - This note discusses the use of capture-mark-recapture methods and log-linear, linear, product models for incomplete tables (Espeland, 1986, Communications in Statistics--Simulation and Computing 15, 405-424) to estimate completeness of reporting in a disease registry and to estimate incompleteness-adjusted incidence rates. The method had several desirable features, including the ability to handle complex experimental designs, to incorporate auxiliary data (that may be related to the likelihood of reporting), to test the contribution of model terms, and to generate point estimates and associated standard errors. PMID- 1290801 TI - A hypothesis for the local control of osteoclast function by Ca2+, nitric oxide and free radicals. AB - Several important conclusions have recently emerged from in vitro studies on the resorptive cell of bone, the osteoclast. First, it has been established that osteoclast function is modulated locally, by changes in the local concentration of Ca2+ caused by hydroxyapatite dissolution. It is thought that activation by Ca2+ of a surface membrane Ca2+ receptor mediates these effects, hence providing a feedback control. Second, a number of molecules produced locally by the endothelial cell, with which the osteoclast is in intimate contact, have been found to affect bone resorption profoundly. For instance, the autocoid nitric oxide strongly inhibits bone resorption. Finally, reactive oxygen species have been found to aid bone resorption and enhance osteoclastic activity directly. Here, we will attempt to integrate these control mechanisms into a unified hypothesis for the local control of bone resorption. PMID- 1290802 TI - Lysis of erythrocytes by Trichomonas vaginalis. AB - The in vitro hemolytic activity of 4 isolates of Trichomonas vaginalis was investigated. Repetitive hemolysis assays of any one isolate showed cyclical fluctuations in hemolytic activity, varying over 24 hr of continuous culture. Maximal hemolytic activity was detected using trichomonads in the lag phase of the growth cycle. Investigations showed that hemolysis was a contact-dependent phenomenon and microscopic investigation of samples showed a significant correlation between hemolysis and attachment of erythrocytes to the trichomonad surface. Quantitative data from cytoadherence assays using [51Cr]-labeled erythrocytes were consistent with these observations. It is suggested that hemolytic activity is dependent upon adherence of red blood cells to the surface of T. vaginalis. PMID- 1290803 TI - ph-dependent hydrophobicity profile of hemagglutinin of influenza virus and its possible relevance in virus fusion. AB - The hydropathy profile of hemagglutinin (HA) subunits HA1 and HA2 of influenza virus X31 and A/PR 8/34 is analyzed at different pH. At neutral pH (7.4) pronounced hydrophobic sequences of HA correspond to the N-terminus and the transmembrane spanning sequence of HA2. At pH 5.0 where influenza virus is known to fuse with biological membranes several hydrophobic sequences in the ectodomain exist which are comparable in both the hydrophobicity and length of the N terminus of HA2. It is suggested that these hydrophobic stretches are important for the fusion complex, in addition to the N-terminal site of HA2. PMID- 1290804 TI - Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro. AB - Bone resorption, in vitro, is often measured as the release of prelabelled 45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 culture medium in serum-free conditions in 0.5 cm2 multiwell culture dishes. Matrix degradation after treatment with parathyroid hormone was assessed by measuring the amount of carboxyterminal telopeptide of type I collagen (ICTP) by RIA. The data on matrix degradation was compared to the release of prelabelled 45Ca from neonatal mouse calvarial bones. We found that the dose-responses for parathyroid hormone-induced release of prelabelled 45Ca and ICTP were identical. IN CONCLUSION: RIA-analysis of the ICTP-release is an easy and accurate method to measure degradation of bone matrix, in vitro. Furthermore, the new dissection technique, described in this report, makes it easy to obtain large amounts of bone samples and thus to perform extensive experiments, e.g. dose-responses for agents that enhance bone resorption. PMID- 1290805 TI - Inhibitors such as staurosporine, H-7 or polymyxin B cannot be used in skeletal muscle to prove the role of protein kinase C on insulin action. AB - The precise role of protein kinase C in insulin action in skeletal muscle is not well defined. Based on the fact that inhibitors of protein kinase C block some insulin effects, it has been concluded that some of the biological actions of insulin are mediated via protein kinase C. In this study, we present evidence that inhibitors of protein kinase C such as staurosporine, H-7 or polymyxin B cannot be used to ascertain the role of protein kinase C in skeletal muscle. This is based on the following experimental evidences: a) staurosporine, H-7 and polymyxin B markedly block in muscle the effect of insulin on System A transport activity; however, this effect of insulin is not mimicked in muscle by TPA induced stimulation of protein kinase C, b) H-7 and polymyxin B block insulin action on System A transport activity in an additive manner to the inhibitory effect of phorbol esters, c) staurosporine, H-7 and polymyxin B block the effect of insulin on lactate production, a process that is activated by insulin and TPA in an additive fashion, and d) staurosporine completely blocks the tyrosine kinase activity of insulin receptors partially purified from rat skeletal muscle. PMID- 1290806 TI - Effect of HDL1 infusion on biliary secretion in perfused rat liver. AB - The effects of HDL1 lipoprotein infusion on biliary lipid secretion were studied in the in vitro model of rat perfused liver. A strong increase in bile flow was observed during and after lipoprotein infusion. This caused a significant rise in cholesterol, phospholipid and bile salt secretions. However, only the percentage of cholesterol increased with respect to the other bile lipids. The changes observed in the cholesterol/phospholipid molar ratio values of liver membrane subfractions (i.e., liver plasma membrane, mitochondria plus lysosomes and microsomes) isolated from the perfused rat liver after HDL1 administration were not significant. PMID- 1290807 TI - [The dynamics of somatosensory and visual evoked potentials as a correlate of reversible states of altered consciousness]. AB - Somatosensory and visual evoked potentials (EPs) of the brain of 17 sensitive subjects (extrasenses) and 12 ordinary healthy subjects were studied. It was found that during extrasensory activity (direct impact, meditation) in comparison to rest values, the amplitude of intermediate and late components of visual and somatosensory EPs of both hemispheres and early components of somatosensory EPs of ipsilateral in relation to stimulation hemisphere diminished 2-4--fold. There was a recovery of these components after discontinuation of extrasensory activity. It is shown that ordinary subjects could not change their EPs when they tried their best to decrease EPs. It is shown that ordinary subjects could not change their EPs when they tried their best to decrease EPs. It is suggested that the ability of extrasenses for reversible changes of their mind by direct adjustment of the activity of the ascending nonspecific systems of the brain and by alterations of interhemispheric relations forms the basis of extrasensory activity. PMID- 1290808 TI - [The role of the liver macrophage system in decreasing the immune complex level of the blood during adaptation to periodic hypoxia]. AB - It has been established that adaptation to intermittent hypoxia in altitude chamber considerably increases the capacity of hepatic macrophagal systems (MFS) to uptake Indian ink particles from the blood as well as immunoglobulin labelled with fluorescein isothiocyanate. There is simultaneous catabolism of labelled albumin in hepatic MFS. It has been suggested that the increased C3b-component of complement system in blood observed in adaptation to hypoxia plays a substantial role in the activation of hepatic MFS. The role of hepatic MFS activation in reducing the number of circulating immune complexes is emphasized as well as its role in therapeutic effect of adaptation in allergic diseases. PMID- 1290809 TI - [The effect of the delta sleep-inducing peptide on the development of toxic brain edema-swelling]. AB - Antiedematic effects of the drugs are connected with their action on the mediator systems. DSIP has a wide range of modulatory effects on the brain mediator systems. DSIP antiedematic effect was studied on the toxic brain edema-swelling (BES) model. Physical characteristics of the nervous tissue such as thickness and wetness were used as evaluation criteria. According to the findings, the doses of 75-100 micrograms/kg DSIP were optimal. It is suggested that DSIP effect on BES is multicomponent and rather complicated. Inhibition of serotonin, noradrenaline and histamine systems and activation of GABA-ergic system by DSIP act as a possible antiedematic mechanism. PMID- 1290810 TI - [The effect of negatively charged liposomes on thrombocyte aggregation induced by ADP]. AB - The incubation of platelet-rich plasma of rats with liposomes has changed cell functional activity. Lipid composition of liposomes modulated the ability of the platelets to respond to ADP. Vesicles, containing phosphatidylserine, phosphatidylinositol or stearylamine inhibited the aggregation by 70, 30 and 40%, respectively. The inhibition of aggregation by phosphatidylserine-containing liposomes was of linear and dose-dependent character. The maximal inhibition was reported at 10-min incubation of liposomes with platelets. The impairment of platelets aggregation can be explained by interactions of liposomes with plasma coagulation factors and blocking the receptors on the platelets membranes. PMID- 1290811 TI - [The effect of synthetic enkephalins on prostaglandin synthesis and lipid peroxidation in the isolated heart during the activation of free-radical processes]. AB - The system Fe(2+)-ascorbate was used for lipid peroxidation (LPO) activation in isolated heart tissue. The stimulation of free radical processes in the myocardium caused a rise in the level of LPO products and a significant lowering of that of prostacyclin. Intravenous injection of synthetic analogues of enkephalins before LPO activation inhibited LPO and resulted in prostacyclin synthesis normalization. The addition of peptides under study into perfusion solution led to a decrease in LPO primary products level and in thromboxane synthesis. PMID- 1290812 TI - [The surface activity of vasopressin and its interaction with artificial and biological membranes]. AB - It was determined that vasopressin has surface active properties and in nanomolic concentrations is capable to incorporate in lipoprotein monolayers which are formed from myocytes plasma membranes. By means of pH-metric and fluorescent analysis it was shown that vasopressin interacts with other membrane structures which have no specific receptors--phosphatidylcholinic liposomes and vesicles of sarcoplasmic reticulum of skeletal muscles causing increasing permeability of phospholipid bilayer for Ca2+ ions. PMID- 1290813 TI - [Biologically active substances from the skin that influence the proliferation and differentiation of cultured human keratinocytes]. AB - Three fractions of biologically active substances of human skin varying in molecular weight (F1 > 15 kD, F2 1.4-15 kD, F3 < 1.4 kD) were tested in primary and regenerating cultures of human epidermal keratinocytes. F1 and F3 caused stimulation of keratinocyte proliferation, F2 inhibited proliferation and enhanced terminal differentiation of epidermal cells. PMID- 1290814 TI - [The effect of natural and synthetic antioxidant polyhydroxynaphthoquinones on cholesterol metabolism in cultured rabbit hepatocytes]. AB - Primary cultures of rabbit hepatocytes were used to examine the effect of natural and synthetic antioxidants--polyhydroxynaphthoquinones (PHNQ) and alpha tocopherol on cholesterol and bile acid synthesis. Histochrome, one of the PHNQ, slightly decreased cholesterol synthesis at concentrations 10-100 microM, whereas alpha-tocopherol stimulated cholesterol synthesis. After administration of histochrome or alpha-tocopherol into culture medium a significant stimulation of bile acid synthesis in dose-dependent manner was observed. The increase of bile acid secretion by histochrome in the presence of physiological concentration of HDL2 was found as well. Since histochrome in contrast to alpha-tocopherol enhanced accumulation of [14C] cholesterol of HDL2 in the hepatocytes, it was concluded that histochrome stimulated bile acid synthesis as a result of increased input of HDL2 cholesterol into hepatocytes. These data suggest that histochrome may exhibit a hypocholesterolemic effect by stimulation of bile acid synthesis and inhibition of cholesterol synthesis. PMID- 1290815 TI - [Tris-2-(oxyethyl)ammonium ortho-cresol acetate--a stimulant of the activity of regenerating hepatocytes]. PMID- 1290816 TI - [The effect of ultrahigh-frequency electromagnetic radiation on learning and memory processes]. AB - Low-intensity electromagnetic field (12.6 cm, 2375 MHz, power density 1 mW/cm2) produced retrograde amnesia in the rat passive avoidance test. No effect was registered of microwave irradiation on the open field behavior and the pain sensitivity. Functional activity of the m-cholinergic receptors decreased, but their number increased in the brain cortex. It is suggested that cholinergic system plays an important role in the effects of electromagnetic field on memory processes. PMID- 1290817 TI - [The immunochemical detection of apoprotein dissociation from particles of very low-density lipoproteins in human blood plasma]. AB - The dissociation of very-low-density lipoprotein (VLDL) apoproteins was studied using immunochemical approaches. The analysis of monospecific antibody binding to apo E, C-II and C-III on VLDL surface showed low apoprotein accessibility for the antibodies while the accessibility of apo C-II and C-III in solution was complete. Lipoprotein preparation dilution resulted in increasing of apo E and C II accessibility. It was suggested that apoprotein dissociation led to apoprotein cluster dissolving on VLDL surface and higher antigen determinant accessibility. The findings confirmed previous theoretical analysis of apoprotein dissociation. PMID- 1290818 TI - [The effect of nitroglycerin, nitrosorbide and nitroprusside on the intracellular content of Ca2+ ions in human lymphocytes]. AB - We used Fura-2 fluorometry to observe the effects of nitroglycerin (NG), isosorbide--2,5--dinitrate (ISDN) and sodium nitroprusside (NP) on basal and mitogen-induced (Con A, 25 micrograms/ml) cytoplasmic Ca++level ([Ca++]) in human blood lymphocytes. It is shown that nitrates dose-dependently decrease Con-A induced increase in [Ca++]i. When compared for the effect on calcium metabolism, NP appeared most potent (IC50 = 4.1 x 10(-7) M). The drug action was not reported when the cells were exposed to Ca(++)-free solution. 120-min preincubation with 10(-4) M NG led to complete abolishment of the ISDN and NG effects. The results suggest that human lymphocytes may be used as an experimental model of nitrates action and mechanisms underlying tolerance to them. PMID- 1290819 TI - [The effect of hydrocortisone on the alkaline proteinase activity in the target organs of rats]. AB - The effect of hydrocortisone on the thymus and liver proteinases activity in the alkaline pH range was studied on rats. It is shown that the alkaline proteinases are activated in the thymus and inhibited in the liver of hormone-treated animals. Possible relationship between the effect of glucocorticoids on protein metabolism and alkaline proteinases activity is suggested. PMID- 1290820 TI - [The effect of cyclosporin A on the islet cells of mice]. AB - The action of immunosuppressive agent ciclosporin A on the insular apparatus was studied with an original method of cytochemical zinc detection in experiments on mice. The drug was found to lower zinc levels in pancreatic beta-cells. In ciclosporin A pretreatment the sensitivity of mice to zinc-binding diabetogenic agent enhanced. PMID- 1290822 TI - [The effect of amiridin on the MPTP-induced Parkinson-like syndrome in monkeys]. AB - Development of behavioral disturbances was investigated during N-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) administration (0,2 mg/kg, i/m, at 48 h. intervals, total dose 11.2-13.2 mg/kg) in experiments on two monkeys Macaca rhesus. MPTP induced the complex of symptoms, which are typical for idiopathic Parkinson's disease. Administration of amiridine (0,25-0,4 mg/kg) to MPTP-treated monkeys caused gradual decline of Parkinson syndrome. Mechanisms of action of amiridine are discussed. PMID- 1290821 TI - [The effect of MPTP on the neuronal uptake of monoamines]. AB - The results of kinetic analysis of synaptosomal uptake of dopamine, noradrenaline, adrenaline and serotonin showed the presence of their own carrier systems with high or low affinity for each monoamine. The low affinity system of the uptake of monoamines by nerve endings differs from extraneuronal one by higher affinity. MPTP noncompetitively inhibits the system of highly effective uptake of the studied monoamines by nerve endings, competitively inhibiting synaptosomal uptake with low affinity of noradrenaline, adrenaline and noncompetitively serotonin and dopamine. The constant values of inhibition showed that MPTP most strongly blocks the system of synaptosomal uptake of low affinity serotonin and approximately 2-times weaker affects its system of high affinity. Carrier systems of high affinity of dopamine, adrenaline and noradrenaline block MPTP 150-500 times weaker than that of serotonin, and as for low affinity--in 2000-4000 times. It may be supposed that synaptosomal uptake of low affinity serotonin is most perceptible to the effect of MPTP and is of a particular importance in the development of Parkinson's disease symptoms. PMID- 1290823 TI - [The protective role of estradiol under extreme conditions]. AB - It has been demonstrated that estradiol increases the resistance of the animals to hemorrhagic shock. Apparently, it is accounted for by its positive effect on cardiovascular system (by stimulation of myocardial contractility, stabilization of ATP and CF pools, inhibition of lipid peroxidation and lysosomal enzymes, etc.). PMID- 1290824 TI - [The effect of ubiquinone-10 on the development of D-galactosamine-induced hepatitis in rats]. AB - It has been shown that prophylactic administration of ubiquinone protects rats liver from the toxic damage by D-galactosamine both on ultrastructural and on cell levels. Ubiquinone administration prevents necrosis in hepatocytes and preserves their ability for compensatory reactions expressed in activation of protein-synthesis regulating structures in the cell. Ubiquinone decreases hyperfermentemia and hyperbilirubinemia as well as prevents the decrease in liver protein content caused by galactosamine. Ubiquinone exerts an antioxidant effect, blocking the induction of lipid peroxidation both in intact and hepatic rats. PMID- 1290825 TI - [The effect of exogenous whole-body hyperthermia on humoral immunity]. AB - We investigated the proliferative responses of spleen cells (SC) to polyclonal mitogens lipopolysaccharide (LPS) and pokeweed mitogen (PWM), immune responses to sheep red cells (SRC) in mice undergoing hyperthermia. There were increased proliferative responses of lymphocytes to PWM if we used mice having rectal temperature 42 degrees C. Thermal shock in mice was accompanied by suppression of immune response. If we used mice suffering from hyperthermia (43-44 degrees C) for 20 minutes; there were decreased proliferative responses of lymphocytes to PWM or LPS for 10-30 days. We observed low immune response to sheep red cells in mice for 5-20 days. The changes of immune response were not revealed on the 40th day after induction of hyperthermia in mice. PMID- 1290826 TI - [The immunohistochemical study of trophoblast beta 1-globulin expression in cancer and in the mucosa of the large intestine]. AB - The expression of pregnancy-specific beta-1-globulin (SP1) was studied in cancer affected and nonaffected colon mucosa. The antigen was revealed in 19 out of 50 (38%) cases of carcinoma and in 1 out of 4 cases of ulcerative colitis. SP1 was found neither in noncancer colon mucosa nor in transitional mucosa and adenomas. The antigen was detected in the epithelium and stromal macrophages of carcinoma. SP1-positive cells were located mainly in the sites of tumor invasion. The results allow considering SP1 the tumor marker suitable for immunohistochemical diagnosis of colon cancer. PMID- 1290827 TI - [The chemiluminescence reactions of the blood neutrophils and of peritoneal exudate cells in Syrian hamsters to the intraperitoneal administration of cellular and microbial materials]. AB - The luminol-dependent chemiluminescence (CL) activity of peritoneal exudate cells and blood neutrophils of Syrian hamsters inoculated intraperitoneally with heat inactivated microbial particles of Candida albicans, (C. albicans), heated irradiated normal cells and native or heated irradiated malignant tumor cells was studied. The inoculation with particles of C. albicans and heated normal cells induced significant activation of CL of peritoneal exudate cells, but did not influence the CL reaction of blood neutrophils. The inoculation of animals with nonheated irradiated tumor cells led to increase of CL response of both peritoneal exudate cells and blood neutrophils. The inoculation with heated irradiated tumor cells did not activate CL of peritoneal exudate cells and led to slight, but long-lasting decrease of CL response of blood neutrophils. PMID- 1290828 TI - [The effect of ascitic fluid globulins on the growth of leukemia P388/DOX and Ehrlich's carcinoma in mice]. AB - The study was performed to investigate the effect of ascitic fluid globulins of tumor on tumor growth and life span of mice. The globulins are shown to shorten the life span of Ehrlich tumor mice from 86.8 to 61.8 days, to increase 3-5-fold the growth rate of Ehrlich carcinoma and P388/DOX tumor. It was found that globulins of ascitic fluids and serum globulins of tumor have equal effects of tumor growth. It is proposed to use globulins of ascitic fluid to study the globulin role in tumor growth. PMID- 1290829 TI - [The effect of a clover extract on the proliferation of human and murine lymphocytes in vitro]. AB - The extracts were prepared from meadow clover harvested at the stages of blossoming and budding. The major biological activity of such extracts is represented by flavonoid compounds. The influence of extracts on the proliferation of peripheral blood mononuclear cells obtained from healthy donors and of inbred mouse splenocytes in vitro was analyzed. Both preparations stimulated cellular proliferation. The lever of stimulating activity correlated with the stage-dependent concentration of flavonoids. PMID- 1290830 TI - [Leukocytolysis and phagocytosis under hyperosmotic conditions]. AB - PAN and leukocytolysis were measured in dog blood placed in hypo- and hypertonic solutions of glycerin and glucose (1:10). It was found that leukocytolytic activity of the substances depends on equimolar concentrations of nonelectrolytes. It is more pronounced in hypo- than in hypertonic conditions. Glycerin is 3-5-times more active than glucose. In concentrations 2.0 M for glycerin and 0.5 M for glucose leukocytolysis is less active. Mononuclears are more resistant than neutrophils in strong solutions. PAN increased by 11-16% in hypotonic solutions. Strong glycerin solutions reduce PAN less than glucose which stimulates the digestive activity. The results can be of use in specific leukolysis tests to diagnose drug allergy. PMID- 1290831 TI - [The seasonal characteristics of the circadian rhythm of hypoxic resistance and convulsive resistance]. AB - Hypoxic and convulsive resistances have daily rhythms, the pattern of which depends on the year season. Latent period of occurrence of epileptic seizures and time of life at the "height" of 11,000 m above the sea level undergo similar changes in autumn and spring. In winter minimal similarity between daily dynamics of each of these resistances and analogous ones in other seasons is observed, but rhythms of tolerance to hypoxia are maximally synchronized with the rhythms of convulsive resistance. In autumn hypoxic and convulsive resistances are minimal. Maximums of these indices are observed in different seasons: for tolerance to hypoxia it is summer, for convulsive resistance--spring. PMID- 1290833 TI - [The nature of the distribution of the individual circulatory biorhythms in schoolchildren (7 to 17 years old) living at different altitudes in the mountains]. AB - Data on individual biorhythms are presented for 270 children aged 7-17 living in the regions situated at 760, 1700 and 2850 m above the sea level. Central hemodynamics was measured by Kubicek et al. method 6 times a day every 6 hours. The analysis of the pilot evidence was conducted by cosinor program, then an original method was introduced which allowed evaluation of the degree of biorhythmologic dispersion in the samples. The findings indicate a significant increase in hemodynamic biorhythm polymorphism and broadening of "biorhythmological norm" in children population aged 7-17 under the middle and high mountain conditions. PMID- 1290832 TI - [The characteristics of the action of the immunomodulator MOP-35 on macrophage 5' nucleotidase activity depending on the time of day]. PMID- 1290834 TI - [The radioisotope labelling of thrombocytes using a monoclonal antibody against membrane glycoproteins IIb-IIIa and the measurement of thrombocyte adhesion/aggregation on the substrate surface]. AB - A new method for platelet labeling based on binding of monoclonal antibody to human platelets has been suggested in this study. Monoclonal antibody VM16a against membrane glycoproteins IIb-IIIa was labeled by 125I and then incubated with platelets. About 70% of added antibody was bound when it was used at the concentrations corresponding to the linear part of the concentration curve (0.5 and 1.0 micrograms/ml). Due to high efficiency of binding 125I-VM16a-labeled platelets were used for the measurement of adhesion/aggregation to the substrate in platelet-rich plasma without washing of the free label. Experiments with washed platelets double labeled with 51Cr and 125I-VM 6a showed high correlation between the data obtained with both labels. The method of platelet labeling has been applied for the assessment of drug action on platelet adhesion/aggregation. Measurements were performed in platelet-rich plasma and adhesion/aggregation was stimulated by ADP and analogue of thromboxane A2, U46619. It was shown/that antianginal drug trapidil strongly inhibited and antiatherogenic drug probucol did not affect platelet adhesion/aggregation stimulated by both agonists. PMID- 1290835 TI - [The permeability of the barrier of the gastrointestinal tract for the macromolecules of polyethylene glycol-4000: an assessment of the mechanism and its reproducibility]. AB - Polyethylene glycol (PEG)-4000 is proposed as a tracer of intestinal macromolecular permeability. The reproducibility of permeability testing with PEG 4000 and the mechanism of its penetration through intestinal mucosa were studied in adult rats. Permeability measurement for PEG-4000 was reproducible when repeated twice for 2 days. This makes it possible to repeat PEG-4000 permeability testing before and after any experimental impact on the intestine. I.p. administration of colchicine to rats (125 micrograms/100 g b. w.) significantly inhibited intestinal absorption of PEG-4000 fed to the animals 3 hours later. Hence, PEG-4000 penetration through the intestinal mucosa is mediated by the system of enterocyte cytoplasmic microtubules. Mucosal permeability for PEG-4000 may be consequently considered as a valuable model of permeability for protein macromolecules. PMID- 1290836 TI - [The ultrastructural reorganization of the neurons in some brain formations during the deprivation of paradoxical sleep]. AB - Electron microscopy was used to study intracellular changes in the dorsal hippocampus, lateral hypothalamic nucleus and pontine reticular formation of rats after 96-hour paradoxical sleep deprivation. It was found that compensative accommodative processes predominate in the majority of neurons. At the same time destructive changes are detected in some cells. In changed neurons the ultrastructural signs of damage to protein-synthesizing apparatus were observed. These changes can be as a result of disturbances of protein biosynthesis. PMID- 1290837 TI - [The marker histochemical detection of glucose-6-phosphate residues in the human placenta]. AB - Glucose-6-phosphate residues were revealed by fine structural analysis using glucose-6-phosphate dehydrogenase-gold conjugate. In human mature placenta specific staining was detected over the stroma of placental villi. Colloidal gold particles were found over the collagen fibrils and reticular lamina of basal membrane. Syncytiotrophoblast cells, fibroblasts, endothelial cells of fetal capillaries avoided labelling. Nucleated blood cells and thrombocytes inside the lumen of fetal capillaries demonstrated intense staining. The present investigation demonstrates histochemically the process of extracellular glycosylation. Glycated collagen fibrils formed channels inside the stroma of placental villi. PMID- 1290838 TI - [The reactivity of the circulating neutrophils in human peripheral blood]. AB - Using cytochemical, biochemical and disc-electrophoretic methods, the degree of extracellular secretion of peroxidase-containing neutrophil granules has been investigated as an index of their functional activity when in contact with antigens of extra- and intra-circulation. It was established that in in vitro contacts of neutrophils with alive and killed microbe culture St. aur., the quantity of the granules in the cells decreased as well as the enzyme activity in them. This is partially due to extracellular secretion of the granules content confirmed by the presence of peroxidase fractions in the solution. Similar results have been obtained for circulating neutrophils and serum of patients with acute pneumonia at the height of the disease. It is hold that antigen-induced extra- and intracellular neutrophil degranulation in the peripheral human blood reflects functional activity of the neutrophils. PMID- 1290839 TI - [Leukocytic shifts following pancreatic resection with a plasma scalpel and cryodestruction]. AB - Two series of experiments were carried out on dogs. In the first series, blood leukocytes count was studied after resection of the pancreas using plasma scalpel. The resection caused two-phase leukocyte reaction: neutrocytosis (phase I) and leukocytosis involving mainly lymphocytes and monocytes (phase II). During the first 24 hours after the resection, a sharp increase of the leukocyte intoxication index (LII) was observed. The second series of experiments was performed using the combination of plasma scalpel and cryodestruction. The graphic curves denoted a sharp fall both in total leukocytic counts and in the different types of leukocytes which were plotted separately (neutrophils, eosinophils, etc.) This can be explained by the absence of the second (lympho monocyte) reaction. Only a slight increase in LII occurred. These results reflect lower degree of the protection and adaptation reactions of leukocytes, this being in favor of a combination of plasma scalpel and cryodestruction during the operation. PMID- 1290840 TI - [Structural-functional transformations of the ileal lymph nodes in pregnancy complicated by blood loss]. AB - The microanatomic organization of iliac lymph nodes was studied in 24 pregnant Wistar rats (pregnancy term 21 days) after simulation of acute hemorrhage in them. A considerable decrease of a relative area occupied by a marginal sinus was revealed. This shows transport functional changes of lymph nodes in pregnancy complicated by hemorrhage. PMID- 1290841 TI - [The astrocyte reaction to an experimental herpes infection]. AB - The experimental research carried out on rabbits was aimed at determination of astrocytes reaction during brain inflammation caused by Herpes simplex virus. The study was made with the help of glia marker. Immunocytochemical findings showed that the earliest structural brain responses to the infection were changes in astrocyte glia. This was evident from the swelling and hypertrophy of vessel crus and from increased number of astrocytes around the vessels. Glia complexes (astrocyte agglomeration) were formed in the affected sites. During the exudative reaction the hyperplastic alterations of astrocytes were not observed. Later the injured spots of brain tissue were replaced by proliferating astrocytes. The conducted investigation has shown the astrocyte glia to be different during different stages of the infectious process. One may suppose that different subtypes of astrocytes response has place during each stage which should be further confirmed. One may also suppose that a similar alterations of astrocytes coincide with interferon and interleukin secretion by these cells. This is suggested to be a structural base of immune response of the brain. PMID- 1290842 TI - Hemoglobin desaturation during sleep and daytime in patients with cystic fibrosis and severe airway obstruction. AB - Transcutaneous hemoglobin saturation by pulse oximetry was evaluated during sleep and for 2-3 h during the day in 31 patients with cystic fibrosis (median age 15.2 years; range 7.6-33.6 years) and severe airway obstruction. Pulse oximetry readings were analyzed as a cumulative percentage of time in which oxygen saturation was < 90% during both sleep and daytime. Each patient was also examined using clinical and radiological scores, spirometry and arterial blood gas analysis. The agreement between arterial and transcutaneous saturation was evaluated in 29 patients. The difference between transcutaneous and arterial saturation was 2.4 +/- 2.0% and it increased as arterial saturation decreased. Clinical and radiological scores and spirometry parameters showed a poor correlation with both overnight and daytime desaturation. An arterial saturation < 94% may indicate a risk of consistent desaturation. This occurred for more than 50% of the time in 11 of 20 patients during sleep and in 5 of 20 patients during daytime hours. PMID- 1290843 TI - The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome. AB - The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome was evaluated in 17 children. Cow's milk was excluded from the diet for at least 14 days without changing previously ineffective prednisone dosage. Six patients with minimal change or mesangial proliferation went into remission 3 to 8 days after elimination of cow's milk. After a period of 2-3 weeks of remission, cow's milk challenge was positive in three patients. After one year on a cow's milk-free diet, two of six patients became milk tolerant and are in remission of NS, one of six became steroid-dependent, two of six are still unable to tolerate cow's milk and are in remission on a cow's milk-free diet and one of six children was lost from observation. The role of cellular mechanisms in steroid-resistant nephrotic syndrome is suggested. PMID- 1290844 TI - Ten-year prognosis for generalized infantile eczema. AB - Forty children treated in our hospital for generalized infantile eczema were re examined at 11-13 years of age. In 7 (18%) children the eczema had disappeared and in 26 (65%) it had become less severe. Unrelated to dermatological status or gender, allergic rhinitis was diagnosed in 31 (78%) and asthma in 21 (53%) children. Only 8 children continued without either of these two conditions. All 32 children with allergic rhinitis and/or asthma showed at least one positive skin test reaction in a test panel of 11 common inhalant and food allergens compared with only 4 of 8 children without either allergic rhinitis or asthma (p < 0.001). Our results showed an improvement of dermatological status in most children with generalized infantile eczema but there was a high risk of a concomitant respiratory allergy and development of allergic rhinitis or asthma. PMID- 1290845 TI - Autologous bone marrow transplantation in children with acute lymphoblastic leukemia. AB - We report 25 children with acute lymphoblastic leukemia (ALL) treated with purged autologous bone marrow transplantation (ABMT) at a single center. Two children with high-risk ALL were transplanted in first remission and 23 with relapsing ALL were transplanted in second (n = 21) or third (n = 2) remission. There was no procedure-related mortality. The median time to engraftment (i.e. to reach a polymorphonuclear cell count of 0.5 x 10(9)/l) was 25 days (range 16-45 days). Seven children relapsed, four within five months after ABMT: 18 of 25 children (72%) are in continuous complete remission after a median follow-up period of 50 months (range 5-71 months). The predicted long-term disease-free survival is 65% in the whole group and 61% in those transplanted after relapse. Relapse-free children returned to normal activities within three months after ABMT. The major side effects were development of cataract and gonadal insufficiency. We consider the results promising, but our data do not allow comparison with results reported from treatment with chemotherapy alone, since some of our patients were referred from other centers and represent a selected patient group. Long-term follow-up of well-defined patient populations is necessary to evaluate the effect of ABMT. PMID- 1290846 TI - Growth during treatment of familial hypercholesterolemia. AB - Treatment of hypercholesterolemic children with restriction of dietary saturated fat may result in an inadequate supply of energy for normal somatic growth. We examined the growth of 30 children with familial hypercholesterolemia, some of whom were also treated with colestipol, a bile acid-binding resin. The median duration of treatment was 8.5 years in 13 patients on diet only, and 5.5 years + 3.5 years in 17 patients treated with diet followed by diet and colestipol. Statistically significant reductions in serum total cholesterol were obtained in both groups. The SD scores for both height/age and weight/age decreased by approximately 0.4 during dietary treatment (p < 0.05), but were not affected by treatment with colestipol. These results document the risk of growth retardation during dietary treatment of children with familial hypercholesterolemia. PMID- 1290847 TI - Anaemia and macrocytosis--unrecognized features in cartilage-hair hypoplasia. AB - Cartilage-hair hypoplasia is an autosomal recessive osteo-chondrodysplasia which results in short stature, sparse hair and impaired cell-mediated immunity. In a study of 88 Finnish patients we found episodes of anaemia and/or macrocytosis during childhood in 86% of the patients. The reticulocyte index was always low in relation to anaemia. Bone marrow examination revealed decreased erythropoiesis in six of eight anaemic patients studied. Anaemia was most prevalent and severe during infancy. Spontaneous recovery occurred before adulthood in all patients except in three infants with fatal hypoplastic anaemia. Sixty-two percent of the patients had had lymphopenia and 24% neutropenia. Presence of anaemia significantly correlated to severity of immunodeficiency and growth failure and to presence of neutropenia. Disordered erythrogenesis is an integral feature of cartilage-hair hypoplasia and may, together with growth failure and immunodeficiency, reflect a generalized defect in cellular proliferation. PMID- 1290849 TI - Low back pain and disability in 14-year-old schoolchildren. AB - In this cross-sectional prevalence study in 1503 14-year-old Finnish schoolchildren (n = 1503) low back pain was found to be the third most common form of pain interfering with schoolwork or leisure time during the past 12 months. The lifetime cumulative incidence of low back pain was 30% and that of sciatica 1.8%. Of the 417 pupils who had experienced low back pain at some time, 39% had suffered during the past month; 65% recovered in one month from the last pain episode, while 35.2% of those reporting disabling low back pain during the past year were aware of recurrent or continual pain. Thus, 7.8% (n = 107) of the whole population could be classified as "low back pain chronics": 86% of the low back pain chronics had trouble with at least one of the daily activities listed, most commonly with sitting at school. Excluding pain in the extremities or sciatica, girls reported various pains more commonly than boys. Moreover, girls reporting recurrent low back pain had more trouble with their daily activities due to pain than boys (p < 0.001), even though the recovery from the last pain episode took the same time in boys and girls. The pupils who had had sciatica at some time, in addition to recurrent low back pain, had more trouble with the 10 daily activities than others with recurrent low back pain (p = 0.014). PMID- 1290848 TI - Magnetic resonance imaging of the brain structures in the posterior fossa in retarded autistic children. AB - Midsagittal magnetic resonance images of the brains of retarded autistic children were compared to those of non-autistic mental retardation patients and controls. We found that the whole brain stem and particularly two of its components (the midbrain and medulla oblongata) were significantly smaller in retarded autistic children and mental retardation cases than in control children. The pons area was significantly smaller in mental retardation cases as compared to control children but did not differ between autistic and control children. Moreover, there was no difference in the brain stem between retarded autistic children and mental retardation cases. We also noted no difference in the cerebellar vermis area among retarded autistic children, mental retardation cases and control children. The ratio of the midbrain to posterior fossa area was significantly smaller only in autistic patients. Although the significance of these results is unknown, further examination of autistic children with a normal IQ is necessary. PMID- 1290850 TI - Relationship between low birth weight and respiratory symptoms in a cohort of primary school children. PMID- 1290851 TI - Guillain-Barre syndrome presenting with severe musculoskeletal pain. AB - Three children with Guillain-Barre syndrome are described who presented with musculoskeletal pain to an orthopaedic clinic or to a paediatric rheumatologist at a children's hospital. In each case, osteomyelitis of the spine was considered to be the most likely diagnosis and bone scans were performed in two of the three patients. Two of the three children required care in an intensive care unit, within hours of diagnosis. Outside of the specialty of neurology, the presentation of Guillain-Barre syndrome with severe muscle pain is not generally well known. With greater awareness of this particular presentation, dangerous delays in diagnosis and inappropriate investigations will be minimized. PMID- 1290852 TI - Bone marrow examination before steroids in thrombocytopenic purpura or arthritis. AB - Corticosteroids were used to treat two children with presumed idiopathic thrombocytopenic purpura and one with juvenile rheumatoid arthritis without examination of the bone marrow. Of the two with presumed idiopathic thrombocytopenic purpura, one had Fanconi's anaemia and the other may have had aplastic anaemia. The third child had acute lymphoblastic leukaemia. The diagnosis of Fanconi's anaemia was delayed. A diagnostic and therapeutic dilemma was caused in the second case. In the third, delayed diagnosis and, perhaps, compromised outlook resulted. These three cases re-emphasize the well aired caveats about the diagnosis of idiopathic thrombocytopenic purpura and juvenile rheumatoid arthritis and provide further support for the arguments of those who believe that if corticosteroids are to be used to treat such children, their bone marrow should be examined first. PMID- 1290853 TI - Microphthalmos with bilateral colobomatous orbital cyst accompanied by polycystic kidney disease and vacuolization of myeloid progenitor cells. AB - A case of microphthalmos with bilateral colobomatous orbital cyst accompanied by polycystic kidney disease and vacuolization of myeloid progenitor cells is presented. Association of these three entities has not been described previously in the literature. PMID- 1290854 TI - TSH-secreting pituitary macroadenoma in an 11-year-old girl. AB - Graves' disease, multinodular toxic goiter or toxic adenoma are the usual causes of hyperthyroidism in children as well as in adults. We report a case of hyperthyroidism due to TSH-secreting pituitary macroadenoma in an 11-year-old girl. The patient was admitted to the Endocrine Department for pituitary function evaluation, five months after transfrontal adenomectomy and pituitary irradiation for a macroadenoma. On admission the patient was clinically hyperthyroid and the work-up established a diagnosis of hyperthyroidism due to TSH-secreting adenoma (high levels of TSH in the face of hyperthyroidism, no TSH response to TRH stimulation, diffuse thyroid goiter without eye signs or pretibial myxedema). Of interest in this case was the fact that: (a) she is the youngest patient reported with hyperthyroidism due to a TSH-secreting macroadenoma and (b) hyperthyroidism was diagnosed after adenomectomy. PMID- 1290855 TI - Cystic adult granulosa cell tumor causing precocious pseudopuberty in a six-year old girl. AB - A very rare occurrence of adult granulosa cell tumor of the ovary (not of the juvenile type) causing precocious pseudopuberty in a six-year-old girl is described. An additional feature of interest was that the tumor appeared entirely cystic. To our knowledge, this condition in such a young premenarchal patient has not been reported previously. PMID- 1290856 TI - Lumbar bone mineral content measured by dual energy X-ray absorptiometry in newborns and infants. AB - Dual energy X-ray absorptiometry (DXA), a non-invasive method for measuring small amounts of mineral, was used to assess the bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (5 vertebrae) in 57 newborns (on day 1 2) and 22 infants (1-24 months of age). A modified high-resolution program (Hologic) allowed us to assess BMC and BMD with a precision higher than 2.4% and 1.5%, respectively. In newborns, BMC and BMD correlated positively with birth weight, body area, length and gestational age: r = 0.73, 0.71, 0.63 and 0.60, respectively, for BMC; and r = 0.59, 0.58, 0.54 and 0.53, respectively, for BMD. In infants, both BMC and BMD were highly correlated with weight, age, length and body area over two years (r = 0.94 or better in each instance). The data provide normal values for lumbar spine BMC and BMD in newborns (gestational age 31-40) and infants up to two years of age; DXA appears to be an excellent and safe tool for pediatric bone mineral measurements. PMID- 1290857 TI - Effects of body movement restraint on cardiac response to auditory stimulation in sleeping infants. AB - When exposed to an unfamiliar and sudden noise, infant rodents may show an abrupt bradycardia, as part of a "fear-paralysis response". The response is enhanced by body movements restraint. To investigate if this reaction is seen in humans, 15 normal infants with a median age of 12 weeks were studied polygraphically. They were exposed to a 100-dB (A) white noise, while sleeping in REM sleep. Each infant was studied in both "unrestrained" and "restrained" conditions. Restraint of body movement was obtained by means of sand bags and tightly-binding bed sheets. During movement restraint, the infants had a significantly greater and earlier decrease in heart rate compared with during the unrestrained condition. No infant had a minimal heart rate less than 95 beats/min. The present observation raises questions about the possible unfavorable effects of tightly wrapped bed sheets around sleeping infants. PMID- 1290858 TI - Narcotic and nicotine effects on the neonatal auditory system. AB - To evaluate narcotic and nicotine effects on the neonatal auditory system, brain stem auditory evoked responses were recorded in 15 infants prenatally exposed to both narcotics and nicotine (median gestational age 38.4 weeks, median birth weight 2820 g), in 15 nicotine exposed infants (gestational age 40.0 weeks, birth weight 3000 g) and in 24 healthy term infants (gestational age 40.1 weeks, birth weight 3310 g) who served as controls. Whereas nicotine-exposed and control infants were similar in all brain stem auditory evoked response measurements, narcotic/nicotine infants had bilaterally increased wave V latencies (left: p = 0.005; right: p = 0.04) and I-V intervals (left: p = 0.02; right: p = 0.01) when compared to controls. Our findings suggest that prenatal narcotic but not nicotine exposure negatively affects maturation or integrity of the neonatal auditory brain stem tract and that neither narcotic nor nicotine exposure is associated with hearing loss in the neonate. PMID- 1290859 TI - Elevated calcitonin gene-related peptide in polycythemic newborn infants. AB - In this study, calcitonin gene-related peptide levels were measured in cord and at 16-36 h of extrauterine life in 43 polycythemic newborns; 20 healthy term infants were also studied as controls. Calcitonin gene-related peptide values were significantly higher in polycythemic neonates in comparison with controls both at delivery and at 16-36 h after birth. Five polycythemic (11.6%) infants who develop hypocalcemia had greater elevated calcitonin gene-related peptide concentrations. Our data suggest that calcitonin gene-related peptide may be implicated in the circulatory adaptation to extrauterine life. In polycythemic neonates, calcitonin gene-related peptide is probably increased to compensate for blood hyperviscosity; in some cases, high calcitonin gene-related peptide concentrations may induce hypocalcemia. PMID- 1290860 TI - Low renal net acid excretion, high calciuria and biochemical signs of sodium deficiency in low-birth-weight infants fed a new low-phosphorus formula. AB - In 11 infants (birth weight greater than 1800 g) fed a new type of humanized formula with a low phosphorus (P) content (calcium (Ca) 11 mmol/l, P 7.2 mmol/l, sodium (Na) 8.3 mmol/l) biochemical parameters of blood, serum and urine were determined. In nine boys Ca and P balances were evaluated also. Renal net acid excretion was low (0.85 mmol/kg/day). Mean concentrations of P and Ca in urine were 0.34 mmol/kg/day (10.5 mg/kg/day) and 0.1 mmol/kg/day (4 mg/kg/day), respectively. In four infants, Ca concentration in urine was, however, greater than 0.15 mmol/kg/day) (6 mg/kg/day). In infants with birth weights greater than 1800 g fed the new, low-P formula, the low renal net acid excretion, the normal P and the high Ca concentrations in urine were comparable to term infants fed human milk. The high calciuria in several infants may be normal physiologic values. However, it remains to be established that the urinary solubility product of infants fed the new, low-P formula is in the same range as those for infants fed human milk. Unexpectedly, low urinary Na excretion (0.26 mmol/kg/day) and increased urinary excretion of aldosterone-18-glucuronide indicated biochemical evidence of Na deficiency secondary to low Na intake and a high weight gain. If the new, low-P formula is to be fed to infants with a birth weight as low as 1800 g. Na content should be higher than in mature human milk because of the often relatively higher weight gain. PMID- 1290861 TI - Non-nutritive sucking does not increase blood levels of gastrin, motilin, insulin and insulin-like growth factor 1 in premature infants receiving enteral feedings. AB - Non-nutritive sucking in premature infants accelerates weight gain for unclear reasons. The effects of non-nutritive sucking on enteral hormone secretion may augment digestion and/or absorption of nutrients. Blood concentrations of gastrin, motilin, insulin and insulin-like growth factor-1 were measured before and 72 h after the initiation of nasogastric feedings in 21 premature infants randomly assigned to either a non-nutritive suckling or control group. Gastrin and motilin concentrations increased significantly after feedings in all infants (mean +/- SEM) (gastrin, 41 +/- 4 to 73 +/- 9 pg/ml, p < 0.01; motilin, 141 +/- 5 to 181 +/- 3 pg/ml, p < 0.01) Pre- and post-feed insulin concentrations were greater in the non-nutritive sucking group receiving bolus feeds than in control infants who were bolus-fed (P < 0.01). Non-nutritive sucking in premature infants does not appear to alter blood concentrations of motilin, gastrin, insulin or insulin-like growth factor-1 three days after initiation of feedings. If changes in the secretion of these hormones are induced by non-nutritive sucking, they may be at a local paracrine level. PMID- 1290862 TI - Atrial natriuretic peptide in the preterm infant. Lack of correlation with natriuresis and diuresis. AB - We assessed the relation of atrial natriuretic peptide (ANP) to renal function on postnatal day 2 and day 5 in preterm infants. Plasma ANP concentration was measured by radioimmunoassay in two groups of preterm infants: group 1, gestational age less than 30 weeks, n = 10; and group 2, gestational age 30-34 weeks, n = 11. The identity of the immunoreactivity as ANP-28 was confirmed by HPLC. Plasma ANP was significantly higher in group 1 than in group 2 on day 2 and day 5 (p < 0.01) and ANP concentration decreased by day 5 in both groups (group 1, p < 0.01; group 2, p < 0.02). The results showed no correlation between plasma ANP concentration and urinary sodium excretion or creatinine clearance, which may be due to a blunted renal response to ANP, but other factors may be involved also. We conclude that preterm infants are able to release large amounts of ANP, but a high plasma ANP concentration does not correlate directly with renal regulation of sodium and water balance. PMID- 1290863 TI - Participation of immune complexes in adenovirus infection. AB - To determine the participation of immune complexes during adenovirus infection, we evaluated serum and necropsy specimens of patients with confirmed adenovirus infection of the lower respiratory tract. In lung and kidney from seven dead patients, immunofluorescence revealed the presence of hexon, immunoglobulins and complement. These patients had clinical manifestations of kidney dysfunction. In dead patients (3/3 in whom serum was available) neither anti-adenovirus antibodies nor adenovirus-specific immune complexes could be found in the final stage of the infection. However, two of these patients had anti-adenovirus antibodies and immune complexes in samples obtained early in the infection. Most patients (16/19) who survived the infection had circulating anti-adenovirus antibodies. Half also had immune complexes specific for adenovirus in some moment of the illness. This suggests that immune complexes arise during respiratory infection by adenovirus, probably contributing to its clinical picture. PMID- 1290864 TI - Role of non-capsulated Haemophilus influenzae as a respiratory pathogen in children. AB - During a 12-month surveillance period from 1981-1982, non-capsulated Haemophilus influenzae was detected in nasopharyngeal aspirates from 64 (14%) of the 449 children hospitalized for middle or lower respiratory infection. An antibody response to H. influenzae was indicated in 15(23%) of the 64 patients with H. influenzae present in nasopharyngeal aspirate and in 10 (3%) of the 385 patients with a negative finding. Thus, serological evidence of H. influenzae infection was demonstrated in 25 (6%) of all the 449 children with respiratory infection. Of 13 patients with cultures positive for H. influenzae acute otitis media, an antibody response was seen in only 4 (30%) patients. H. influenzae infection was associated with infections caused by other microbes in 20 children (80%), with viral infections in 60% and with pneumococcal infections in 24% of cases. An infection focus was present in 15 (79%) of the 25 patients with H. influenzae infection; pneumonia was present in 10 cases and acute otitis media in 9 cases. Non-specific laboratory evidence of bacterial infection was seen in 11 patients (58%); C-reactive protein was increased in 7 and erythrocyte sedimentation rate in 9 patients. It is concluded that non-capsulated H. influenzae is a genuine respiratory pathogen in children. H. influenzae infections appear to be secondary to preceding viral or other bacterial infections in children who are carriers of this strain. PMID- 1290865 TI - Role of Moraxella (Branhamella) catarrhalis as a respiratory pathogen in children. AB - During a 12-month surveillance period in 1981-1982, Moraxella catarrhalis was detected in cultures from nasopharyngeal aspirates from 76 (17%) of 449 children hospitalized with middle or lower respiratory tract infection. Seroconversion to M. catarrhalis was positive in 4 (5%) of the 76 patients with M. catarrhalis present in nasopharyngeal aspirates and in 4 (1%) of 373 patients with a negative finding. Although children with respiratory tract infections were often colonized by the organism, this was rarely the infective agent of the middle or lower airways. Four of 8 patients with seroconversion to M. catarrhalis exhibited a concomitant RSV infection. The carriage of this species was more closely associated with parainfluenza virus infections. Serological responses to M. catarrhalis were not associated with acute otitis media, and were also rare in children with pneumonia. It is concluded that bronchopulmonary infections caused by M. catarrhalis are rare in children, and that M. catarrhalis aetiology need not be considered in the selection of antibiotics in cases of community-acquired pneumonia or other infections of the middle or lower respiratory tract affecting primarily healthy children. PMID- 1290866 TI - Nested amplification protocol for the detection of Mycobacterium tuberculosis. AB - Several methods for rapid diagnosis of tuberculosis have been devised through DNA amplification. However, the chemically strong cell wall of the species, the presumptively low numbers of organisms and their uneven distribution in clinical samples, and the lack of a "gold standard" for diagnosing tuberculosis, have hindered the routine clinical use of this method. In a pediatric patient group, these factors are more perplexing. To circumvent these problems, we made use of nested amplification and developed a standard protocol for extracting DNA from various forms of clinical samples which were suitable to our clinical laboratory. It is our impression that the overall sensitivity, including technical bias accompanying this method, is equal to, or at least greater than, that of culture. Most notably, the rapidity in obtaining results and the simplicity in handling, storage and transfer of samples are the principal advantages of this method. PMID- 1290867 TI - Public health nursing in schools: perceptions of public school administrators. AB - In localities throughout the country, in lieu of school nurses, nursing services are provided to county schools by public health nurses. The multiple demands placed upon these nurses and counties' fund limitations suggested this study of school administrators' perceptions of nursing responsibility and nursing activities. Administrators of elementary, middle, and high schools were surveyed by questionnaire as to (1) area(s) of nursing responsibility they considered most important and (2) their rank ordering of importance of individual nursing activities. Supervision activities related to communicable disease and immunization garnered the highest ratings. The only significant difference in ranking between groups of administrators was that health counseling for students was ranked higher by high school administrators, whereas health education for parents was ranked higher at the elementary level. PMID- 1290868 TI - Scabies: update on diagnosis and treatment. AB - Scabies, a pruritic, contagious skin disease, is endemic in our society. It is especially prevalent in schools and day care centers. Close physical contact, such as that of children playing, is required for transmission. During the past decade a new therapeutic agent has replaced standard therapy. Diagnosis, symptoms, possible complications and treatment options are discussed. PMID- 1290869 TI - Nursing practice management: David is a 9-year-old student diagnosed with Ewing's sarcoma. PMID- 1290870 TI - DNR orders in school? PMID- 1290871 TI - Color-vision deficiency--what does it mean? AB - Color-vision deficiency is a disorder affecting a significant proportion of the population, yet it remains poorly understood by school personnel as well as the general public. This article examines the many ways abnormal color perception affects peoples' lives. The role of the school nurse in detection of the problem, plus education and counseling of the affected student, parents, and teachers is discussed. PMID- 1290873 TI - Confluence of ethical and economic issues in the development and adoption of high technology approaches in clinical care. PMID- 1290875 TI - Toward a comprehensive reform of U.S. health care. PMID- 1290876 TI - The health care crisis: danger or opportunity? PMID- 1290877 TI - Health care in Canada: public access and freedom of choice. PMID- 1290878 TI - HIV infected professionals versus patient's rights. PMID- 1290879 TI - A national health plan for the United States. PMID- 1290880 TI - New Jersey State Health Plan: for the year 2000. PMID- 1290881 TI - Health care in New Jersey: a call for change. PMID- 1290882 TI - Revisioning U.S. health care: some priorities from a biblical tradition. PMID- 1290884 TI - Emergency Medical Treatment and Active Labor Act. PMID- 1290883 TI - Mock hospital ethics committee: the role of ethics committees in resource distribution. Roundtable discussion. PMID- 1290885 TI - The need for health care reform. PMID- 1290886 TI - Participatory democracy in health care: the role of the responsible citizen. PMID- 1290887 TI - Casemix update. PMID- 1290888 TI - A five year review of anaerobic, necrotizing soft tissue infections: a nursing perspective. AB - Anaerobic necrotizing soft tissue infections are known for their devastating effects of tissue destruction and death. These infections may occur as a result of trauma, surgical intervention or occur spontaneously in predisposed individuals. They are caused by a wide range of anaerobic organisms and may be categorised according to the tissue involvement as Necrotizing Fasciitis and Myonecrosis. A five year review of patients admitted for hyperbaric oxygen (HBO) therapy and requiring intensive care revealed a patient group numbering 25, roughly equally divided between the two classifications of tissue involvement. Trauma was an aetiological factor in 5 of these cases. Cancer and diabetes mellitus were also prominent aetiological factors. Treatment consisted of the triad of early selective/aggressive surgery, high dose antibiotic therapy and HBO therapy. The mortality of the group was 25%. Delay in treatment was associated with increased mortality. Nursing care, for this particular patient group is demanding, requiring particular attention to wound care, analgesia, transport, psychosocial care of patient with mutilating wounds, nutrition and temperature homeostasis. It is a cause for concern that two cases occurred after elective orthopaedic procedures requiring the application of plaster of paris (POP) cast over a leg. PMID- 1290889 TI - The Australian Resuscitation Council Advanced Life Support Committee. PMID- 1290891 TI - Nurse prescribing: one step forwards, two steps back? PMID- 1290890 TI - Writing for publication. PMID- 1290892 TI - Pressure sores: the result of bad nursing? PMID- 1290893 TI - Creating the optimum environment for pressure area care. AB - Pressure area care is often thought to be only 'skin deep' but this does not fulfil the philosophy of holistic patient care. Nurses, as the pivot of the multidisciplinary team, must fully assess each patient's needs and implement care based on this assessment, thereby creating the optimum environment for pressure area care. PMID- 1290894 TI - Episiotomy vs perineal tear: which is less traumatic? AB - Episiotomy is a well-established procedure in obstetric care worldwide. This article examines the available research and literature on episiotomy vs perineal tear to determine whether there is any evidence that episiotomy is indeed less traumatic than allowing the perineum to tear. PMID- 1290895 TI - Children in critical care: how parents cope. AB - This article examines the parental role in the critical care setting. Parents' perceptions of stress and stressors are discussed, and the coping strategies developed by families to deal with them are identified. The implications of the findings are discussed in the light of current practice. PMID- 1290896 TI - Health visiting an elderly couple. AB - Health visitors play an important role in their involvement with the elderly population. As Parkinson's disease becomes increasingly prevalent among elderly people, a multidisciplinary approach to treatment and care is essential in the holistic assessment and management of the condition. The importance of the carer in the life of the elderly person with Parkinson's disease cannot be overemphasized. Effective two-way communication and involvement of both the sufferer and main carer in decisions about treatment and care are essential. Effective communication between all members of the primary healthcare team is necessary for continuity of care and support. The use of the Neuman System Model in this case demonstrates the way in which tools of assessment can influence our perception of the client, the type of information obtained and the care and support clients receive. PMID- 1290897 TI - Creativity in nurse education. AB - Educationalists have been accused of suppressing, or at least not encouraging, creativity in nursing students. Is this still the case or are the changes in nurse education helping to reverse this trend? PMID- 1290898 TI - Sleeping with patients. PMID- 1290899 TI - Management of an inadequately ventilated patient. AB - The aim of this article is to help the nurse aider recognize and manage breathing problems other than those associated with upper airway obstruction. Although the emphasis is on nurse aid in the work environment, inadequate ventilation may have to be dealt with in any nurse-aid situation. PMID- 1290900 TI - How to be successful when applying for a postregistration course: 1. AB - The recent publication of the Tomlinson Report (Department of Health, 1992) will see far-reaching changes to the employment prospects for many nurses. Therefore, nurses need to be fully aware of the available opportunities when applying for a course place to ensure a successful outcome. PMID- 1290901 TI - Healthcare in Kenya: learning from a Third World country. AB - Kenya's healthcare problems are exacerbated by illiteracy, widespread communities, poor sanitation in some areas, and tribal customs and traditions. This article gives an overview of Kenya's healthcare system that was gained by the author during a study tour to Kenya in March 1991. PMID- 1290902 TI - The development and history of chewing gum. PMID- 1290903 TI - Dental health in the reign of Louis XIV: anecdotes in the memoirs of Saint-Simon. PMID- 1290904 TI - Dosimetry in dental radiology. PMID- 1290905 TI - The history of maxillary sinus surgery from Leonardo da Vinci until today. PMID- 1290906 TI - History of sedation and general anesthesia in dentistry: remarks in the Ether Dome, October 10, 1990. PMID- 1290907 TI - War's impact on dental materials. PMID- 1290908 TI - The broach. PMID- 1290909 TI - Reaction of the human gingival tissue to different suture materials used in periodontal surgery. AB - The gingival reaction to 4 different suture materials used in periodontal surgery was studied in 36 patients. The gingiva was sutured prior to surgery and biopsies were taken at 3, 7 and 14 days to observe the tissue reaction. The histological examination showed that silk caused the most intense and longest inflammatory response. Polyester and perlon provoked shorter, less intense tissue reactions than silk, and nylon caused the least inflammatory response, with earlier tissue repair. PMID- 1290910 TI - Influence of age on the reactivity of the BANA test among Brazilian children. AB - Three hundred and twenty samples of subgingival plaque were obtained from 80 caucasian girls, ranging from 10 to 13 years of age. The samples were analyzed to verify the influence of age upon colonization of the gingival sulcus by microorganisms potentially pathogenic to the periodontal tissues. The gingival and plaque status were evaluated through the gingival index (GI) and plaque index (PlI) and the microflora was assessed by the enzymatic method benzoyl-arginine naphthylamide (BANA). The results of the BANA test were positive for 62.50% of the tested individuals and 40% of the examined sites. The influence of age was statistically significant on BANA reactivity, and the number of positive sites was greater at 11 (57.5%) than at 12 years (28.8%). PMID- 1290911 TI - Surface tension of several drugs used in endodontics. AB - Surface tension of various drugs used in endodontic therapy was studied by the capillary method. Drugs of the phenol group--eugenol, paramonochlorophenol, tricresol-formalin and phenol--presented very low surface tension. The association of a detergent to the solution of calcium hydroxide reduced its surface tension by half. PMID- 1290912 TI - Dental pain and sleep. Experimental study on guinea pigs (Cavia porcellus). AB - The relationship between pain and sleep was studied by using electrocorticograms (ECoG) taken from guinea pigs submitted to noxious stimulation (NS) of the dental pulp of the upper incisors, after local application of serotonin (5-HT) to the obex (a brain region inductive to sleep). The results showed that the dental electrical stimulation of the sleepy animal was capable of keeping this animal in a state of vigilance and excitation, suggesting that the trigeminal system probably acts on the sleep regulating centers. PMID- 1290914 TI - Dental teaching in Brazil and the need for change. PMID- 1290913 TI - Effect of polishing burs and stones on the micro-hardness of dental amalgam. AB - Square standard cavities were prepared in human teeth and restored with amalgam obtained from alloys of different trade-marks. Twenty-four hours after condensation, excess amalgam was removed from three of the four margins, each with a different rotatory instrument (number 4 bur, multiblade finishing bur, and fine green stone). No rotatory instrument was used on the fourth margin (control), and this control was polished with pumice and zinc-oxide pastes and Sweeney's brushes. Vickers' tests for micro-hardness of the amalgam were performed on the four margins of the restorations. The restorations were then submitted to metallographic polishing, and a second micro-hardness measurement was made seven days later. The statistical analysis of the data showed that micro hardness values were higher at the margins on which no rotatory instruments were used. The lowest micro-hardness values were found at the margins where finishing and/or round burs were used. Polishing with fine green stones gave intermediate values. PMID- 1290915 TI - Treatment of dens invaginatus in a maxillary canine case report. PMID- 1290916 TI - Maxillary lateral incisor with two roots--case report. PMID- 1290917 TI - Root form and canal anatomy of maxillary first premolars. AB - The external and internal anatomy of 240 extracted, maxillary first premolars was studied. The external anatomy was studied by measuring each tooth and by observing the direction of the root curvatures from the facial and proximal aspects. The internal anatomy of the pulp cavity was studied by a method of making the teeth translucent. A total of 55.8% of the teeth had a single root, 41.7% had two roots and 2.5% had three roots. Considering all of the first premolars, 17.1% had one canal, 80.4% had two canals and 2.5% had three canals. PMID- 1290918 TI - A method to evaluate and compare roentgenograms. AB - A simple and practical method is suggested to evaluate and compare roentgenograms concerning optical density and contrast. The method is specifically indicated for research in which a metallic stepwedge penetrometer and a photodensitometer are used. A PC computer may be optionally employed for the mathematical and statistical processing of the data. PMID- 1290919 TI - Effects of baroceptor and cardiopulmonary reflexes on neural control of heart rate in normal man, as assessed by power spectral analysis. AB - This study was designed to establish the neurally-mediated effects of baroceptor and cardiopulmonary reflexes on heart rate in normal subjects. We therefore studied the effects of various interventions, able to modify the activity of arterial baroreceptors and cardiopulmonary receptors, on the power spectrum of the R-R interval in nine healthy men. To confirm the efficacy of these interventions left ventricular volume was monitored using a portable radionuclide probe. Isosorbide dinitrate (5 mgm sublingually) while sitting unloads both baroreceptors and the cardiopulmonary receptors; it decreased left ventricular end-diastolic volume (p < 0.01) and the mean R-R interval (p < 0.005), increased the power of the low-frequency (LF) component of the R-R interval (p < 0.01), decreased the power of the high-frequency (HF) component (p < 0.005) and increased the LF/HF ratio (p < 0.05). The application of cuffs around the thighs in the supine position, which unloads only cardiopulmonary receptors, decreased left ventricular end-diastolic volume (p < 0.05) but did not affect mean R-R interval, LF component, HF component and LF/HF ratio (p > or = 0.10). Leg raising, which loads only cardiopulmonary receptors, increased left ventricular end-diastolic volume (p < 0.05) and did not affect the mean R-R interval, LF component, HF component and LF/HF ratio (p > or = 0.10). In conclusion, our data suggest that, in normal man, baroreceptor unloading increased sympathetic and decreased parasympathetic neural control of heart rate; cardiopulmonary reflexes do not appear to have a direct neurally mediated effect on heart rate. PMID- 1290920 TI - A comparison of the effects of the selective peripheral alpha 1-blocker terazosin with the selective beta 1-blocker atenolol on blood pressure, exercise performance and the lipid profile in mild-to-moderate essential hypertension. AB - The effects of six weeks of treatment with the selective peripheral alpha 1 adrenoceptor blocker terazosin, or the selective beta 1-adrenoceptor blocker atenolol on blood pressure, exercise performance and blood lipid profile were compared in a single-blind, randomized, crossover study of 17 patients with mild to-moderate essential hypertension. Although both drugs significantly reduced blood pressure at rest, atenolol caused a larger fall in supine blood pressure (11/11 and 7.5/7.0 mmHg, atenolol and terazosin, respectively; p < 0.001). Both treatments controlled the pressor response to exercise, although a greater reduction in diastolic blood pressure was observed at the end of exercise on terazosin (74.0 +/- 5.7 and 91.6 +/- 4.0 mmHg, terazosin and atenolol, respectively; p < 0.01). Alpha 1-blocker therapy was not associated with any measurable improvement or deterioration in cardiopulmonary performance and exercise duration. Unlike atenolol, terazosin therapy had the potentially beneficial effect of reducing serum total cholesterol levels and increasing the high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol ratio. PMID- 1290921 TI - Heart rate variability in smokers, sedentary and aerobically fit individuals. AB - To test the hypothesis that certain lifestyles may affect cardiovascular regulatory mechanisms, heart rate variability (HRV) among three age-matched groups with different lifestyles (smoking, sedentary and aerobically fit) were compared. Heart rate variability was defined as the difference in heart rate during inhalation vs. exhalation. Heart rate was obtained from normal RR intervals, using a continuous electrocardiogram recording, while subjects were seated and breathing at an augmented tidal volume, and also while subjects were standing and breathing at normal tidal volumes. In the physically active group, heart rate variability was significantly elevated at rest as well as during some of the autonomic tests, when compared to the sedentary and smoker groups (p < 0.05). A hypothesis to explain this finding is that smoking or a sedentary lifestyle reduces vagal tone, whereas a physically active lifestyle, resulting in enhanced aerobic fitness, increases vagal tone. These findings may have cardiovascular health implications. PMID- 1290922 TI - Sympathoinhibition and hypotension in carotid sinus hypersensitivity. AB - Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position. PMID- 1290923 TI - Influence of posture on cardiorespiratory reflexes in normal subjects and patients with diabetes mellitus. AB - This study was designed to assess the effect of patient posture, either sitting or supine, on the results and diagnostic yield of tests of cardiorespiratory reflexes on 25 normal subject controls and 128 patients with diabetes mellitus. The heart rate changes during slow breathing at 6 per minute (delta R6) and during a Valsalva manoeuvre (highest heart rate during manoeuvre divided by lowest heart rate within 30 s after manoeuvre; Valsalva ratio) were measured from the electrocardiographic signal and tachometry. In control subjects, heart rate changes during slow breathing averaged 25.0 when sitting and 21.3 when supine (p < 0.01); Valsalva ratio averaged 1.90 and 1.83 (p > 0.2) respectively. In diabetic patients, mean values for heart rate changes during slow breathing were 6.1 and 5.1, and mean values for Valsalva ratio were 1.23 and 1.28 in sitting and supine postures respectively. According to our normal limits, heart rate changes during slow breathing was below normal in 109 patients tested when sitting and in 113 tested when supine, and Valsalva ratio was abnormal in 103 and 95 respectively. These results indicate that subject posture is an important variable of cardio-respiratory reflex testing, and should be standardized to allow comparisons of individual results. PMID- 1290924 TI - Tachyphylaxis to capsaicin-induced cough and its reversal by indomethacin, in patients with the sinobronchial syndrome. AB - Cough reflex testing with capsaicin has been used to study the pathophysiology of the cough reflex and the antitussive effects of various drugs. Although the reproducibility of capsaicin-induced cough has been well established in normal subjects, it is not known if prior challenge with capsaicin reduces the subsequent cough response to inhaled capsaicin in patients with the sinobronchial syndrome, a condition characterized by chronic upper and lower airway inflammation. Measurement of the capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was repeated four times at intervals of 15, 30 and 60 min in eleven patients with the SBS and ten normal subjects. The cough thresholds at 15, 30 and 60 min were greater than the initial value in patients with the SBS but not in normal subjects. In addition, we examined the effect of 4 days treatment with indomethacin (100 mg/day) on the cough thresholds measured twice at an interval of 15 min in eight patients with the SBS. Indomethacin increased the initial cough threshold and reduced the increment in the post-15 min cough threshold from the initial value compared with placebo, thus reducing the tachyphylaxis. These results indicate that chronic airway inflammation may be responsible for the decreased response (tachyphylaxis) to repeated inhalation of capsaicin, and suggest that cyclooxygenase products released by the airway inflammation may be involved in tachyphylaxis, cough receptor sensitivity to inhaled capsaicin, or both, in patients with the SBS. PMID- 1290925 TI - Autonomic neuropathy and immunological abnormalities in Chagas' disease. AB - Chagas' disease (American Trypanosomiasis) is caused by infection with the haemoflagellate parasite Trypanosoma cruzi, which is transmitted from animals to man by the Reduviidae bug. The human disease is characterized by two phases. In the first (acute phase) parasitaemia is high and general symptoms variable. The next, which is lifelong (chronic phase), is characterized by inflammatory lesions in cardiac and skeletal muscle, gastrointestinal, the autonomic nervous system. Parasites are difficult to detect in blood and affected tissues. Lesions within the autonomic nervous system, lead to development of cardiomyopathy, megaoesophagus and megacolon. The discrepancy between the profusion of inflammatory lesions and the absence of parasites suggests the development of autoimmunity probably of a cell-mediated type. Several autoimmune abnormalities have been noted during Trypanosoma cruzi infection. These include suppression of the specific response to autoantibodies directed against antigens located in the endocardium and in nerves, and development of cell-mediated immunity against host antigens (cytotoxic T- and delayed type hypersensitivity T-cells). These autoimmune disorders are thought to be responsible for much of the pathological damage in chronic Chagas' disease. PMID- 1290926 TI - What are enzyme structures telling us? AB - Most globular proteins are waxy inside and soapy outside. Their compact structures are stabilised by the hydrophobic effect which is mainly entropic, and by hydrogen bonds and dispersion forces which are mainly enthalpic. Structurally homologous proteins tend to share a common set of internal sites from which polar residues are excluded, even if they share little sequence homology. Electrostatic effects are dominant in enzyme catalysis. The active sites of enzymes are generally buried in clefts or cavities where dipoles tend to be oriented so as to optimise the pKas of ionizable amino acid side chains for catalysis; substrates are clamped close by to maximise electrostatic interactions. The activities of many enzymes have long been known to be controlled by allosteric effects or by induced fit. Some serine proteinase inhibitors have evolved yet another control mechanism: this is a spring-loaded safety catch that makes them revert to their latent, stable, inactive form unless the catch is kept in the 'loaded' position by another molecule. PMID- 1290927 TI - Substrate recognition by proteinases. AB - The molecular recognition of limited proteolytic site substrates by serine proteinases has been compared and contrasted to the recognition of serine proteinase inhibitors, utilising the coordinate sets contained in the Brookhaven Protein Databank. Most families of these inhibitors are known to possess a structurally conserved recognition motif at their reactive site-binding loops. Structural comparisons with trypsin limited proteolytic sites revealed that the in situ conformation of these substrates bears little resemblance to the inhibitor-binding loops. Assuming that both inhibitors and substrates bind to the proteinase in the same manner, segmental mobility would be required to permit substrates to adopt an 'inhibitor-like' binding conformation, which is presumed to be necessary for proteolysis. Modelling experiments have been conducted to attempt to introduce such a conformation into tryptic limited proteolytic segments of the native proteins, to test the ability of the limited proteolytic sites to alter their geometry. Further to this, the conformational parameters of accessibility, protrusion, mobility and secondary structure have been analysed and incorporated into a predictive algorithm to assign likely limited proteolytic sites within native protein structures. PMID- 1290928 TI - Catalytic mechanism of glycogen phosphorylase. AB - Proposals for the catalytic mechanism of glycogen phosphorylase based on crystallographic studies with the T-state form of the enzyme are reviewed in the light of new structural data from studies with the R-state enzyme. The observed position for a sulfate ion at the catalytic site and the crystallographic binding studies of glucose-1-P to the R-state enzyme support the previous proposals in which the 5'-phosphate group of the essential cofactor pyridoxal phosphate functions as an acid-base to promote attack by the substrate phosphate on the polysaccharide substrate. The sulfate (phosphate) recognition site, which is fully formed only in the R state, comprises interactions from the side chains of Arg-569 and Lys-574 and the main chain nitrogen of Gly-135 at the start of an alpha-helix. The interactions of the cofactor 5'-phosphate do not change between the T and the R state. Other groups on the protein play important roles in binding the substrate but are not involved in the catalytic reaction. The presumed reactive conformation of bound substrate has been observed with heptulose-2-P in the T state and in this conformation stereoelectronic arguments suggest the C(1)-O(1) bond is weakened. For the natural substrate glucose-1-P it is proposed that the reactive conformation is achieved only in the presence of the oligosaccharide component in the reactive ternary enzyme-substrate complex. The phosphate recognition sites are discussed. PMID- 1290929 TI - cAMP-dependent protein kinase and the protein kinase family. AB - The structure of the catalytic subunit of cAMP-dependent protein kinase, the first protein kinase structure to be solved, is reviewed. The general architecture of the enzyme is described as well as the active site regions associated with substrate binding and catalysis. In particular, the unique features of the protein kinase nucleotide fold are outlined. While the catalytic subunit is one of the simplest of the protein kinases, it nevertheless serves as a structural framework for the catalytic core of the entire protein kinase family which now includes over 200 important regulatory enzymes. The essential and conserved features of this core are summarized, and a preliminary model of myosin light-chain kinase, based on the structure of the catalytic subunit, is also discussed. PMID- 1290930 TI - Mechanism of allosteric transition of bacterial L-lactate dehydrogenase. AB - The allosteric behaviour of L-lactate dehydrogenase (L lactate:NAD+oxidoreductase, EC 1.1.1.27, LDH) from Bifidobacterium longum aM101-2 was studied by means of the subunit hybridization technique as well as X-ray crystallography. Homotropic allosteric response of the LDH activity was found against the concentration of its substrate, pyruvate. Heterotropic allosteric activation of the enzyme was induced by the addition of fructose 1,6-bisphosphate (FBP). Two mutant enzymes, which had either altered sensitivity to FBP or altered substrate specificity from pyruvate to oxaloacetate, were made by site-directed mutagenesis. Hybrid LDHs, between the wild and the mutant LDHs, were made by in vivo subunit hybridization using double transformation of Escherichia coli with two plasmids carrying either the gene of wild or mutant LDH. Introduction of only one desensitized mutant subunit to the LDH changed the characteristic of the wild enzyme to that of the mutant LDH. Kinetic studies on hybrid enzymes consisting of subunits having different substrate specificity indicated that there was a strong cooperative interaction among subunits. These results strongly support the idea that the allosteric change of the LDH fits the concerted-symmetry model proposed by Monod, Wyman, and Changeux. We analysed the crystallographic structure of the LDH having low affinity to substrate at 1.9 A resolution. By the comparison of the structure with that of other LDHs, we concluded that the conformational transition of the LDH was mainly caused by concerted rotations of subunits. PMID- 1290932 TI - Pathway of protein folding. AB - The order of formation of substructures in the folding of barnase has been determined by a protein engineering procedure and corroborated and complemented by NMR experiments. Early events are the formation of the centre of the beta sheet and the C-terminus of the major alpha-helix. These later dock to form the major hydrophobic core. Structural studies of fragments of barnase in solution show that a peptide that spans the major alpha-helix is found to contain a significant fraction of its C-terminal region in the helical structures. The formation of the native secondary structure as an early event in folding and in isolated fragments is accompanied by considerable burial of hydrophobic surfaces. The experimental data support a model for protein folding in which initiation sites in secondary structure are driven by local hydrophobic interactions, and their docking via further hydrophobic interactions drives the formation of tertiary structure. PMID- 1290931 TI - Dissection of protein structure and folding by directed mutagenesis. AB - The lysozyme from bacteriophage T4 is being used as a model system to determine the roles of individual amino acids in the folding and stability of a typical globular protein. One general finding is that the protein is very adaptable, being able to accommodate many potentially destabilizing replacements. In order to determine the importance of 'alpha-helix propensity' in protein stability, different replacements have been made within alpha-helical segments of T4 lysozyme. Several such substitutions of the form Xaa-->Ala increase the stability of the protein, supporting the idea that alanine is a strongly helix-favouring amino acid. It is possible to engineer a protein that has up to ten alanines in succession, yet still folds and has normal activity. This illustrates the redundancy that is present in the amino acid sequence. A number of 'cavity creating' mutants of the form Leu-->Ala have been constructed to understand better the nature of hydrophobic stabilization. The structural consequences of these mutations differ from site to site. In some cases the protein structure hardly changes at all; in other cases removal of the wild-type side-chain allows surrounding atoms to move in and occupy the vacated space, although a cavity always remains. The destabilization of the protein associated with these cavity creating mutations also varies from case to case. The results suggest how to reconcile recent conflicting reports concerning the strength of the hydrophobic effect in proteins. PMID- 1290933 TI - Exploring the molecular mechanism of dihydrofolate reductase. AB - A description of the transition-state complex of the enzyme dihydrofolate reductase is presented based upon extensive crystallographic studies of substrate/cofactor complexes from various sources. Structural elements of DHFR have been identified which contribute in different ways to effect the chemical step involving protonation and hydride transfer. Emphasis is placed upon residues, structures and solvent which create the appropriate environment for stabilization of the positively charged carbenium ions which are thought to be developed in the transition state of the enzyme-catalysed reaction. Changes in the positions of the substrate and cofactor in the active site which must occur to achieve the correct geometry for hydride transfer are also described. Finally, the structures of several site-directed mutants of DHFR are presented and the results are discussed in the context of the proposed structure for the transition state. PMID- 1290935 TI - Cold destabilisation of enzymes. AB - The thermal stability profile of chymotrypsinogen has been investigated in the temperature range 230-340 K, with special emphasis on the phenomenon of cold instability. Differential scanning calorimetry was used to study the heat capacities of the native and denatured protein in undercooled solution and the results were combined with those obtained by spectrophotometry at ordinary temperatures. The partial heat capacities of both forms decrease with decreasing temperature, assuming negative values. In the experimentally accessible temperature range (above the spontaneous nucleation temperature of ice) the heat capacity difference delta C is found to be positive with a non-linear temperature dependence. delta C is predicted to change sign at some low temperature which cannot, however, be reached by experiment for chymotrypsinogen. In contrast to earlier studies, covering a much more limited temperature range and having to employ an additional destabilisation by means of pH and/or chaotropes, the present findings permit the construction of a more reliable thermodynamic stability profile and related properties. These differ in important details from those reported for other proteins, but based on measurements only in the neighbourhood of the heat-denaturation temperature. The thermodynamic characteristics are, however, in good agreement with earlier predictions and with recent low-temperature measurements on the tetrameric enzyme lactate dehydrogenase. PMID- 1290934 TI - Simulation analysis of triose phosphate isomerase: conformational transition and catalysis. AB - A theoretical approach is employed to study the catalysis of the dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde 3-phosphate (GAP) reaction by the enzyme triose phosphate isomerase (TIM). The conformational change in a loop involved in protecting the active site from solvent is examined by use of X-ray data and molecular dynamics simulations. A mixed quantum-mechanics and molecular mechanics potential is used to determine the energy surface along the reaction path. The calculations address the role of the enzyme in lowering the barrier to reaction and provide a decomposition into specific residue contributions. To obtain a clearer understanding of the electronic effects, the polarization of the substrate carbonyl group by the active site residues is examined and compared with FTIR measurements on the wild-type and mutant forms of the enzyme. PMID- 1290936 TI - Three-dimensional profiles for analysing protein sequence-structure relationships. AB - In the method of 3D (three-dimensional) profiles, each residue position in a protein is characterized by its environment and is represented by a row of 20 numbers in a table, the profile. These numbers are the statistical preferences (called 3D-1D scores) of each of the 20 amino acids for this environment. A profile is computed from the coordinates of a protein model, and it gives a score S for any amino acid sequence folded as the model. To date 3D profiles have found three applications. The first is to identify other protein sequences which are folded in the same general pattern as the structure from which the profile was prepared. These are sequences which have high scores for the profile computed from the model. The second is to assess the validity of protein models, however determined. Correct models are found to give profiles that have high scores for their own amino acid sequences, and incorrect models are found to have lower scores. The example of the X-ray structure determination of diphtheria toxin is discussed. The third application is to assess which is the stable oligomeric state of a folded protein. Several examples suggest that the highest profile score for a sequence is achieved when the protein is aggregated into its most stable oligomeric state. PMID- 1290937 TI - Vibrational Raman optical activity of enzymes. AB - Advances in Raman optical activity (ROA) instrumentation, based on the employment of a backscattering geometry together with a back-thinned CCD detector and a single-grating spectrograph with a holographic edge filter, have now enhanced the sensitivity to the level necessary to provide vibrational ROA spectra of proteins in aqueous solution. Early results show at least four separate regions in protein ROA spectra associated with vibrations of the backbone which appear to characterize the alpha-helix, beta-sheet, reverse turn and random-coil secondary conformation content. Side-group ROA features also appear, with tryptophan particularly prominent in lysozyme and alpha-lactalbumin. ROA should become a sensitive new probe of protein folding and ligand-induced conformational change in aqueous solution. PMID- 1290938 TI - Modelling the structure and function of enzymes by machine learning. AB - A machine learning program, GOLEM, has been applied to two problems: (1) the prediction of protein secondary structure from sequence and (2) modelling a quantitative structure-activity relationship in drug design. GOLEM takes as input observations and combines them with background knowledge of chemistry to yield rules expressed as stereochemical principles for prediction. The secondary structure prediction was explored on the alpha/alpha class of proteins; on an unrelated test set it yielded 81% accuracy. The rules from GOLEM defined patterns of residues forming alpha-helices. The system studied for drug design was the activities of trimethoprim analogues binding to E. coli dihydrofolate reductase. The GOLEM rules were a better model than standard regression approaches. More importantly, these rules described the chemical properties of the enzyme-binding site that were in broad agreement with the crystallographic structure. PMID- 1290939 TI - Functional zinc-binding motifs in enzymes and DNA-binding proteins. AB - Zinc is now known to be an integral component of a large number and variety of enzymes and proteins involved in virtually all aspects of metabolism, thus accounting for the fact that this element is essential for growth and development. The chemistry of zinc, superficially bland, in reality has turned out to be ideally appropriate and versatile for the unexpected development of multiple and unique chemical structures which biology has used for specific life processes. The present discussion will centre on those distinctive zinc-binding motifs that are critical both to enzyme function and the expression of the genetic message. X-Ray diffraction structure determination of 15 zinc enzymes belonging to IUB classes I-IV provide absolute standards of reference for the identity and nature of zinc ligands in their families. Three types of zinc enzyme binding motifs emerge through analysis of these: catalytic, coactive or cocatalytic, and structural. In contrast to zinc enzymes virtually all DNA binding proteins contain multiple zinc atoms. With the availability of NMR and X ray structure analyses three distinct motifs now emerge for those: zinc fingers, twists and clusters. PMID- 1290940 TI - Structure and mechanism of D-xylose isomerase. AB - The action of xylose isomerase depends on the presence of two divalent cations. Crystal structure analyses of the free enzyme, and of the enzyme bound to a variety of substrates and inhibitors, have provided models for a number of distinct intermediates along the reaction pathway. These models, in turn, have suggested detailed mechanisms for the various chemical steps of the reaction: a ring opening catalysed by an activated histidine, a hydride-shift isomerization, and a ring closure which may be facilitated by a polarised water molecule. PMID- 1290941 TI - Three-dimensional structure of galactose oxidase: an enzyme with a built-in secondary cofactor. AB - Galactose oxidase is a copper-containing enzyme, which catalyses stereospecific oxidation of primary alcohols. The three-dimensional structure of the enzyme has been determined in this study by X-ray crystallography at high resolution. The molecule is almost entirely composed of beta-structures and consists of three domains. The arrangement of 28 beta-strands in the second domain is of particular interest, having seven four-stranded antiparallel beta-sheets with pseudo sevenfold symmetry. The copper site has square-pyramidal coordination with two histidines, one tyrosine and one exogenous ligand at the equatorial sites and another tyrosine at the axial site. The most intriguing structural feature is a covalent bond between C epsilon 1 of Tyr-272, which is one of the equatorial ligands, and S gamma of Cys-228. This unexpected thioether bond, and Trp-290 stacked above it, strongly supports the presence of a tyrosine free radical in the enzyme as a 'built-in' secondary cofactor. Calculation of the molecular surface shows a small pocket at the copper site and suggests a substrate-binding model, which can explain the substrate specificity. A model for the catalytic mechanism, involving a tyrosine free radical and basic tryptophan, is also proposed. PMID- 1290942 TI - Induced-fit movements in adenylate kinases. AB - Adenylate kinases have an M(r) around 23,000 which classifies them among the smallest phosphoryl group transferring enzymes. In order to prevent phosphoryl transfer to water, i.e. hydrolysis, these enzymes undergo induced-fit motions on substrate binding and assemble/disassemble their catalytic centres during each reaction cycle. Details of these processes have been derived from several X-ray structure analyses. The disturbance of these analyses by crystal-packing effects is discussed. PMID- 1290943 TI - Structural and evolutionary relationships in lipase mechanism and activation. AB - Lipases that break down triglycerides to monoglycerides and glycerol are characterised by low or no activity in water; in the presence of an oil/water interface, however, their activity increases markedly. The structural and chemical basis for this phenomenon, referred to as interfacial activation, has been revealed by the crystal structures of a fungal lipase and a human pancreatic lipase which evidently have a divergent evolutionary history. These studies reveal that: (1) In both enzymes the catalytic sidechains are Asp:His:Ser, the same as occur in the serine proteases. The active atoms on this catalytic triad have essentially identical stereochemistry in the serine proteases and in these two lipases. The amino acids themselves, however, have quite different conformations and orientations. (2) In both enzymes the catalytic groups are buried and inaccessible to the surrounding solvent. Burial in these two lipases is brought about by a small stretch of helix (the lid) which sits over the active site. (3) In both enzymes this helical lid presents non-polar sidechains over the catalytic group, and polar sidechains to the enzyme surface. Although the 'lids' are very similar in construction in the two enzymes, they belong to very different parts of the polypeptide chain. (4) Although the amino acid sequences have no identity (except at the active serine) the two enzymes show a similar architectural framework consisting of a central five-stranded parallel beta sheet structure. The catalytic groups decorate this beta sheet structure in a strikingly similar way though there are also some significant differences. The crystal structure of the complex between the fungal enzyme and a substrate analogue demonstrates how the helical lid is displaced to reveal the active site. The movement of the lid also greatly enlarges the non-polar surface at the active surfaces and buries previously exposed polar residues. The movement of the lid also helps to create the appropriate movement at the oxyanion hole. It is possible to define the stereochemistry at the active site and to identify the positioning of the fatty acid and the glycerol moieties. PMID- 1290944 TI - A business perspective of dentistry today. PMID- 1290945 TI - Computer-aided ceramic reconstructions. PMID- 1290946 TI - Noise pollution and hearing loss in the dental office. PMID- 1290947 TI - Aesthetic landmarks--guidelines of reality and illusion. PMID- 1290948 TI - Amalgam. Your questions answered. PMID- 1290949 TI - Dentistry in Venezuela. Manpower and womanpower. PMID- 1290950 TI - Saliva. Something to dip into. PMID- 1290952 TI - The influence of age, size, pubertal status and renal factors on urinary growth hormone excretion in normal children and adolescents. AB - Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth hormone is stressed before application of this test to children with growth disorders. PMID- 1290951 TI - Role of platelet derived growth factor in bone cell function. AB - PDGF is a mitogen for cells of the osteoblastic lineage. PDGF is present in the systemic circulation and is locally synthesized by skeletal cells. The systemic form primarily contains PDGF B chains, which are intrinsically more active than PDGF A subunits, the forms secreted by normal bone cells. PDGF AA is regulated by other growth factors and cytokines, which modulate its binding to osteoblastic receptors and its synthesis by skeletal cells. The exact role of PDGF in bone remodelling is still uncertain and current information suggests that this factor has a function in the response to inflammation and wound healing. PMID- 1290953 TI - Tissue specific responses to clenbuterol; temporal changes in protein metabolism of striated muscle and visceral tissues from rats. AB - The beta-adrenoceptor agonist, clenbuterol, was administered orally to male weanling rats for a period of up to 10 days. The composition and fractional rate of protein synthesis (Ks) in skeletal and cardiac muscle, gut and liver were determined. There were few changes in the visceral tissues, but there was marked protein accretion in the muscles. The results suggested that in skeletal muscles there is an increase in both Ks and the amount of protein synthesised per unit RNA. In cardiac muscle, the results indicated that there was only a very transient increase in Ks and that changes in translational capacity (RNA/prot) may account in part for the increase in protein content. It is concluded that the mechanistic basis for the increased protein gain may be different between skeletal and cardiac muscles. PMID- 1290954 TI - Evolution of the growth hormone-releasing factor (GRF) family of peptides. AB - 1. The primordial GRF may have arisen quite early in evolutionary history, at or prior to (i.e. should immunoreactivity data be confirmed in invertebrates) the appearance of jawed vertebrates (Gnathostomates). A common evolutionary pathway using gene duplication may have been utilized to generate the GRF super-family of peptides. As most members of this peptide superfamily are produced in the gastrointestinal tract, the question is posed whether the GRF may have similar origins. 2. It is suggested that the GRF superfamily has two major branches: a) GRF; PRP/PACAP; VIP/PHI; secretin and b) Glucagon/GLP-1/GLP-2. GIP is likely to be a member of the glucagon branch. The two branches may be attributable to gene duplication encoding an ancestral molecule. These gene duplications are likely to have occurred prior to the evolution of vertebrates (conservatively 400-500 million years ago, and possibly 1 billion years ago). It is probable that peptides homologous to GRF, VIP and glucagon will be isolated from invertebrates. These invertebrate sequences will shed further light upon the evolution of this peptide superfamily. 3. Throughout the GRF superfamily, amphiphilic alpha-helical secondary structures represent preferred bioactive conformations. It is assumed that stable, ordered secondary structures conferring enhanced ligand-receptor interactions were conserved due to selective pressures. 4. It is well documented that hypothalamic GRF stimulates adenohypophyseal GH secretion in a variety of species. Thus far, the physiological effects of GRF have been attributed thus to the elevation of GH, and possibly also IGF-I. Recent data suggests a more liberal view; that GRF may also have direct actions in fetal/placental development, reproduction and immune function. Furthermore these direct effects may be mediated via GRF from either hypothalamic or extrahypothalamic (e.g. placenta, testes, ovary, leukocyte) sources. In conclusion, a great wealth of information has accumulated since the discovery of GRF. Examination of the GRF peptide superfamily from an evolutionary perspective has revealed new insights into the synthesis, processing, degradation, conformation and activities of these molecules. Knowledge obtained from these evolutionary comparisons has also become particularly useful in contemporary peptide drug design, which may be liberally viewed as a form of 'artificial evolution' (i.e. the selective pressure being clinical/veterinary requirements for more potent, long-acting GRF analogs). PMID- 1290955 TI - The present status in all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia patients: further understanding and comprehensive strategy are required in the future. AB - All-trans retinoic acid (ATRA) has recently been recognized as the first line therapeutic agent in the treatment of patients with acute promyelocytic leukemia (APL). The extraordinary high remission rate achieved by ATRA in comparison with other chemotherapeutic agents suggested that ATRA differentiation induction therapy seemed superior to conventional chemotherapy for APL patients. However, after the great excitement aroused after the initial successes, we have to take stock and examine in detail several problems which have emerged preventing us from improving the clinical outcome in APL. Maintenance in order to prolong remission and prevention of or retreatment for the relapse are the major subjects of concern at present. Efforts should be made either to keep ATRA effective for APL patients or to resensitize the relapsing patients for repeated ATRA therapy. The administration of ATRA should be carefully adapted in accordance with the individual patient's condition. From both conceptual and practical points of view, ATRA differentiation therapy should be combined with chemotherapy, bone marrow transplantation and biomodifier treatment. Thus, a more comprehensive strategy must be planned and developed in the near future. Using molecular biological techniques, the diagnosis of APL can be more precisely made and the course of the disease more closely monitored. The central dogma, still to be revealed, is the relationship between APL pathogenesis, the chromosome translocation present with the relevant molecular alterations and the response to ATRA treatment. Current studies in all these above fields have provided us with a deeper understanding of the pathogenesis of APL and the physiological function and curative action of ATRA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290956 TI - The therapeutic potential of interleukin-1 and tumor necrosis factor on hematopoietic stem cells. AB - Dose intensity is emerging as a crucial determinant of success in cytotoxic cancer therapy; however, myelosuppression presents as one of the major complications encountered with increased dose intensity. Therefore, investigators are looking at the use of cytokine administration in combination with cytotoxic therapy to overcome this problem. Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) have been shown to be beneficial in protecting the hematopoietic system from radiation and chemotherapy. In this report, we give an overview of studies using IL-1 and TNF-alpha as protective agents and discuss possible mechanisms involved in their protective action. Mice pretreated with IL 1 and/or TNF-alpha were shown to be protected from the lethal effects of radiation and it has been suggested that the mechanism for this protection may be through the production of the antioxidant enzyme manganese superoxide dismutase. Similarly, aldehyde dehydrogenase, an enzyme important in the metabolic pathway of cyclophosphamide compounds, has been implicated as being important in the protection of hematopoietic cells from 4-hydroperoxycyclophosphamide. While IL-1 and TNF-alpha stimulate both of these enzymes, other mechanisms are probably also operative for other forms of chemotherapy, i.e. IL-1 and TNF-alpha were shown to protect hematopoietic progenitors from phenylketophosphamide, a cyclophosphamide derivative that is not metabolized by the enzyme aldehyde dehydrogenase. Furthermore, malignant as well as normal cells may possess receptors for these cytokines; therefore, IL-1 and TNF-alpha will have to be selective in their protection. They must be capable of protecting normal hematopoietic cells while rendering malignant cells susceptible to the toxic actions of the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290957 TI - Platelet storage pool deficiency, leukemia, and myelodysplastic syndromes. AB - Abnormalities in platelet dense granules, small intracellular organelles containing ATP, ADP, calcium, serotonin, and pyrophosphate, have frequently been reported in patients with leukemia and myeloproliferative disorders, particularly acute and chronic myelogenous leukemia. Recent studies of a family which includes several members with an autosomal dominant dense granule deficiency condition show an association between the presence of this form of dense granule deficiency and the development of acute myelogenous leukemia. Studies in two additional patients, one with the Monosomy 7 syndrome and the second with a myelodysplastic syndrome, revealed a defect in platelet dense granules. This defect appears to be due to an abnormality in the formation of these granules rather than the presence of empty vesicular structures or decreased contents due to activation associated secretion. The results suggest that the defect in platelet dense granules associated with leukemia or myelodysplastic syndromes may result from a chromosome alteration in the megakaryocyte cell line leading to decreased formation of dense granules. Studies in the family with an inherited bleeding disorder suggest that a gene coding for a protein important for the formation of dense granules is located adjacent to a gene which, when abnormal, may predispose to the development of leukemia. PMID- 1290958 TI - Acute tumor lysis syndrome in hematologic malignancies. AB - Acute tumor lysis syndrome (ATLS) represents one of the most urgent of all oncologic treatment related complications. This is due not only to its broad impact on organ dysfunction, but also to its relative ease of prevention and treatment when aware of its potential threat. Despite anecdotal experiences of ATLS in settings outside the use of chemotherapy, the majority of patients susceptible to ATLS can be predicted using clinical as well as laboratory parameters and prophylaxis can prevent this potentially lethal consequence of otherwise successful cancer therapeutics. This review article will attempt to bring the critical aspects involving ATLS together in order to delineate the pathophysiology as well as treatment of this generally avoidable entity. PMID- 1290959 TI - The use of fluconazole prophylaxis in patients with chemotherapy-induced neutropenia. AB - Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise. PMID- 1290960 TI - Comparison of the survivals between bone marrow transplantation and chemotherapy for acute leukemia in first remission--a Japanese single institution study. AB - The outcome of sixty-four patients with acute leukemia in first remission who had been treated with either bone marrow transplantation (BMT) or conventional chemotherapy was retrospectively evaluated (a median follow-up of 37 months). Among them, 26 patients (age range; 14-42 years) received allogeneic BMT from HLA identical siblings and 38 patients (age range; 13-43 years) who had no HLA identical donors undertook the continued combination chemotherapy. Kaplan-Meier product-limit estimate of actuarial survival of acute myelogenous leukemia (AML) patients was 48.9% for the BMT group and 15.7% for the chemotherapy group (p = not significant, NS). For acute lymphoblastic leukemia (ALL) patients, the survival following BMT was 80.2% and was significantly higher than that of the chemotherapy group of 33.3% (p < 0.05). The disease-free survival of AML and ALL for the BMT group was 34.3% and 36.5%, respectively, which was higher than that of the chemotherapy group (16.7% and 23.4%, respectively (p = NS)). These findings in our Japanese single institution study suggested that BMT may be the treatment of choice for adult patients with acute leukemia in first remission if they had suitable donors and that more effective therapeutic regimens were necessary for patients without compatible donors in order to obtain the longer remission duration. PMID- 1290961 TI - AMSA combination chemotherapy in patients with acute myelogenous leukemia unsuitable for standard antileukemic treatment. AB - Forty-eight patients with acute myelogenous leukemia (AML) not eligible for anthracycline or mitoxantrone treatment, mostly due to cardiac contraindications, were given aggressive therapy using m-amsacrine (AMSA) in combination with conventional or high-dose cytarabine for remission induction. Twenty-nine patients (60.4%) responded to treatment, and complete remission was attained in 19 (39.6%), partial remission in 4 (8.3%) and death in bone marrow aplasia without detectable blasts in 6 patients (12.5%). Median time to granulocyte recovery was 32 days, median duration of relapse-free survival 199 days. One patient experienced a serious cardiac adverse event; nausea and vomiting were observed in 73%, diarrhea in 44%, and hepatoxicity in 29% of patients. All potentially AMSA-related side effects were fully reversible, and a lethal complication did not occur. It is concluded that combination chemotherapy with AMSA and Ara-C is also effective and tolerable in leukemic patients in whom cardiotoxic drugs are contraindicated. PMID- 1290962 TI - Prognostic value of the histologic classification of peripheral T-cell lymphoma: a clinico-pathologic study of 71 HTLV-1 negative cases. AB - The histologic and clinical features of 71 cases of peripheral T-cell lymphoma (PTCL) have been studied. All patients were HTLV-1 negative. The T-cell phenotype was demonstrated by immunohistochemistry on cryostat sections (41 cases) and paraffin-embedded sections (30 cases). All cases were histologically classified according to the updated Kiel classification of non-Hodgkin's lymphoma (low and high-grade) and according to a Working Formulation (WF)-based classification (predominantly small cells, mixed small and large cells, and predominantly large cells). Most cases were in the high-grade group according to both classifications. The prognostic value of these two classifications was comparatively assessed. The analysis of the actuarial survival curves showed that, by using the updated Kiel classification, low-grade PTCL had a survival probability higher than high-grade PTCL although the difference was not statistically significant. Similar results were obtained when the WF-based classification was applied: furthermore, actuarial survival curves of mixed small and large cell PTCL, and of large cell PTCL were rather similar, thus indicating that differentiating these two categories has a limited prognostic value. PMID- 1290963 TI - Leukaemic intermediate lymphocytic lymphomas: analysis of twelve cases diagnosed by morphology. AB - Twelve cases of leukaemic intermediate diffuse lymphocytic lymphoma (ILL), diagnosed by morphology, were analysed. The morphology of the ILL cells was so typical that it allowed ready distinction from chronic lymphocytic leukaemia (CLL) and other related B cell disorders. All cases were of B derivation, had strong mu and chi or lambda immunoglobulin (Ig) staining, were CD5 and FMC7 positive and CD10 negative. Cytogenetic abnormalities were found in 8 patients all having t(11;14)(q13;q32). DNA analysis revealed a relatively high incidence of hypoploidy. At diagnosis all the patients (9 males, 5 females; median age 68) had a low degree of absolute lymphocytosis but the disease was advanced and mostly widespread. The course of the disease appears to be aggressive and incurable with conventional combination chemotherapy. PMID- 1290964 TI - Modulation of GM-CSF receptor beta-subunit and interleukin-6 receptor mRNA expression in a human megakaryocytic leukemia cell line. AB - Our present study was designed to clarify the mechanism by which the same megakaryocyte progenitor cells respond to various cytokines at different stages of megakaryocyte development. We examined the changes in mRNA expression of granulocyte macrophage colony-stimulating factor receptor beta-subunit (GM-CSFR beta-subunit), which was a common subunit of a high-affinity interleukin-3 receptor (IL-3R) and a high-affinity GM-CSFR, and interleukin-6 receptor (IL-6R) during megakaryocyte development in a human megakaryocytic leukemia cell line (CMK) which could proliferate and/or differentiate in the presence of 12-O tetradecanoylphorbol 13-acetate (TPA), IL-3, GM-CSF, and IL-6. We found that GM CSFR beta-subunit mRNA was expressed constitutively in CMK cells and was transiently down-regulated by TPA and IL-6, while the expression of IL-6R mRNA was increased by TPA in association with the differentiation of megakaryocytes. Furthermore, the TPA-induced down-regulation of GM-CSFR beta-subunit mRNA expression and its recovery were blocked by cycloheximide (CHX), a protein synthesis inhibitor, suggesting that these modulations required de novo protein synthesis. These findings imply that multi-lineage cytokines such as GM-CSF and IL-3 may contribute preferentially to the regulation of the earlier development of megakaryocyte progenitor cells with high densities of multi-lineage cytokine receptors, while IL-6 may be limited in its action to supporting the maturation of more differentiated megakaryocyte progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1290965 TI - Obstructive solitary bronchial non-Hodgkin's lymphoma--a rare presentation of primary extranodal disease. AB - Endobronchial involvement by non-Hodgkin's lymphoma (NHL) is uncommon and usually occurs in the presence of more generalised disease. Solitary endobronchial lymphoma in the absence of disease elsewhere is extremely rare. In this report we describe a patient with an obstructing endobronchial mass which was the initial manifestation of NHL. The patient was treated initially with radiotherapy followed by cyclic combination chemotherapy with initial complete resolution of the endobronchial disease. However, he subsequently developed widespread lymphoma. This unusual presentation of NHL is discussed and the relevant literature is reviewed. PMID- 1290967 TI - Bone marrow necrosis and human parvovirus associated infection preceding an Ph1+ acute lymphoblastic leukemia. AB - A case of bone marrow necrosis associated with a serologically documented recent Parvovirus B 19 infection which preceded the development of PH1+ acute lymphoblastic leukemia is reported. No conclusions can be drawn on the basis of a single case but the question of the role of human Parvovirus B19 in the pathogenesis of bone marrow necrosis is discussed. It is suggested that the virus may act as a co-factor for the induction of bone marrow necrosis, in some cases. PMID- 1290968 TI - Private, for-profit geriatric case management. PMID- 1290966 TI - Granulocytic sarcomas of small intestine and brain are associated with acute myelomonocytic leukaemia with abnormal eosinophils and inversion of chromosome 16. AB - We report two cases of acute myelomonocytic leukaemia with abnormal eosinophils (M4Eo) in which the presenting feature was small bowel obstruction. We suggest there is a unique clinicopathological association between small intestine involvement with leukaemia and the M4Eo subtype. Central nervous system involvement by myeloblastoma occurred in one of the two cases which is a recognised feature of M4Eo and should necessitate prophylaxis with intrathecal therapy. Inversion of chromosome 16 which is a cytogenetic marker for M4Eo was demonstrable in one of the two cases. PMID- 1290969 TI - The evolution of private geriatric care management. Guidelines for responsible practice. AB - Fueled by a series of demographic, occupational, and programmatic trends, private firms providing care management services to the elderly and their families have experienced rapid growth. A range of leadership challenges faces social workers entering this specialty. Exemplary ethical and professional behavior will ultimately determine the extent to which private geriatric care managers become a central component of the gerontological services network. PMID- 1290970 TI - Private geriatric care management: how families are served. AB - This article provides a synopsis of a 1987 study of private care management and looks at the reasons why individuals and families seek out and use the services of private care managers. Among the most common reasons are: to negotiate the long-term-care system, to get help in filling out forms, to get objective assistance in assessing options, to mediate family conflict over what to do, and to plan and monitor the care of family members. PMID- 1290971 TI - The business of for-profit case management. AB - The growing number of older Americans is creating a major market for home care and case management services. Large corporations are entering the field to cash in on the beckoning profits. Individuals who are moving from not-for-profit case management agencies to start their own for-profit businesses bring solid values and much needed experience. However, they must learn to respect their knowledge for its financial worth and to apply solid business skills if they are to succeed against the large diversified corporations entering the field. PMID- 1290972 TI - Factors related to successful goal attainment in case management. AB - Goal planning is fundamental to the case management process. Manager and client identify specific long-term goals and then systematically break them down into the incremental behaviors needed to be accomplished to achieve each goal. The goal-setting process may fail as a result of four types of factors: (1) behavioral, (2) cognitive, (3) affective, and (4) environmental. To decrease the likelihood of failure, case managers must be knowledgeable about goal planning. They must help the client set goals that are expressed positively, that are client focused, realistic and achievable, measurable, and easily understood, with one observable outcome per goal. For both case manager and client, setting and attaining goals must be viewed as part of a continuing learning process, rather than a success-failure dichotomy. PMID- 1290973 TI - Across the great divide. Integrating acute, post-acute and long-term care. AB - The importance of integrating acute, post-acute and long-term care is underscored by analyses of the extent of medical complexity among the SHMO enrollee population that qualified for a long-term care benefit on functional (not medical) criteria. In the SHMO programs, initiatives to promote integration of services at all levels of care have largely come from the care management units. Integrative practices will vary in different organizational settings. Examples from two very different SHMO sites illustrate how integrative practices are implemented. It is concluded that in order to serve adequately a medically complex and functionally impaired elder population a key function of care management is to develop cooperative relationships, and mechanisms for information exchange, with providers at all system levels, reaching across the great divide between the acute and long-term care systems. PMID- 1290974 TI - [Urinary excretion of magnesium and calcium in patients with pulmonary squamous cell carcinoma treated by ionizing radiation]. AB - Radiotherapy in patients with squamous cell lung cancer produced an increase of urinary magnesium and calcium secretion. This is probably due to the cytolysis of malignant cells and shifting of the acid--base balance toward acidity values. This interpretation is justified by the significant correlation between the regression of tumor and increased secretion of the intercellular cation- magnesium. PMID- 1290975 TI - [Increased activity of erythrocyte superoxide dismutase as the result of adaptation to long-term oxygen therapy]. AB - Activity of erythrocyte superoxide dismutase (SOD) was assessed in 17 patients with decompensated chronic cor pulmonale and in 15 healthy volunteers. Also the serum levels of uric acid and hematological parameters were analyzed. Recordings were made in ten day intervals during long term oxygen therapy. The authors have found the increase of SOD activity in the treated patients which can be interpreted as a generalized adaptation of the organism to long term oxygen therapy. PMID- 1290976 TI - [Effect of TFX (Polfa) on the course of experimental bacterial infections in mice treated with ciprofloxacin, amikacin and cefoperazone]. AB - The effect of TFX-Polfa administered alone or with three antibiotics on the survival time in mice infected with E.coli and S.aureus was estimated. TFX has been administered 48, 24, 2 hours before and 24, 48 and 72 hours after infection, in doses of 10 mg/kg of body weight. Ciprobay has been administered 2 hours after infection, and every 24 hours during the experiment in dose of 15, 7.5 and 3.75 mg/kg of body weight. Amikin has been used in doses of 7.5, 3.75 and 1.87 mg/kg of body weight, Cefobid in doses of 30, 15 and 7.5 mg/kg of body weight. The antibiotics have been administered 2 hours after infection and every 12 hours to the end of experiment. Animals have been observed 10 days after infection. The positive effect of TFX on the survival time in mice infected with E.coli has been observed, but this preparation has given a little effect on the tested parameter in mice infected with S.aureus. Best antibacterial effect of Ciprobay and Amikin has been observed after administration of clinical doses. However, simultaneous therapy with TFX and tested antibiotics resulted in various (positive and negative) effects on the survival time during 10 days of observation. PMID- 1290977 TI - [Effect of ofloxacin, ciprofloxacin and nalidixic acid on serum theophylline level in patients treated with methylxanthine preparations]. AB - The effect of two new quinolones, ofloxacin and ciprofloxacin and nalidixic acid on serum theophylline level in 17 asthma patients treated with methylxanthines was evaluated. Each quinolone was administered one tablet twice daily to all patients for three days. Blood samples were taken before quinolone administration and 1 h, 3h and 5 h after taking the drug on the first day. Last sample was taken 5 h after quinolone administration on the third day of therapy. The serum theophylline concentration was determined by 3 M Theo FAST test. It was found that in the patients treated with ciprofloxacin serum theophylline level in all samples was significantly higher as compared with the control sample. In the patients receiving ofloxacin the theophylline level only 1 h after receiving the drug the increase was statistical significant. Nalidixic acid had no influence on serum theophylline concentration. As these studies show, the new quinolones should be applied with great caution in patients treated with high doses of methylxanthines or in patients with decreased methylxanthines clearance. In patients with chronic obturative diseases and pulmonary infections the safer drug would appear to be ofloxacin. PMID- 1290978 TI - [Allergen-specific IgG-4 (asIgG-4) in atopic diseases]. PMID- 1290979 TI - [Natural history of pulmonary hypertension in chronic obstructive lung diseases and the usefulness of the simple noninvasive methods of its diagnosis]. AB - In 47 patients with chronic obstructive pulmonary disease and 19 patients with idiopathic pulmonary fibrosis pulmonary haemodynamics were studied. Pulmonary arterial pressure was compared with non-invasive lung function tests, ecg and the chest X-ray. Correlations between pulmonary arterial pressure and some of those parameters were found. Investigations were repeated after 3 or 5 years depending on severity of pulmonary hypertension initially found. The progression of pulmonary hypertension was found. It was accompanied by intensification of non invasive indices of pulmonary hypertension. More than half of patients with initially severe pulmonary hypertension (> or = 30 mmg Hg) did not survive 3 years. PMID- 1290980 TI - [Prevalence of smoking among the staff of the Medical Academy and the State Clinical Hospital No. 1 in Gdansk and among 5th-year medical students]. AB - Addiction to smoking was assessed in workers of the Medical School, Central Clinical Hospital in Gdansk and 50 medical students basing on the results of a simple questionnaire. 400 questionnaires were distributed. 287 were returned. 79% of the responders were females. 61.3% of the questioned subjects were smokers. 53.7% of the females were smokers, where as only 50% of the males smoked. The highest percentage of smokers was found in the group of orderlies, administrative workers and nurses (62-73%). Most of the health workers acknowledged knowing about the harmful effect of tobacco smoking. 95% believed that anti-smoking measures are inadequate in Poland. PMID- 1290981 TI - [Castleman tumor]. AB - A case of a mediastinal benign tumor in a 56 year old male is presented. The tumor was detected during a routine chest radiographic examination. The patient was asymptomatic. During thoracotomy two tumors were found. One was localized in the middle mediastinum the other in the posterior mediastinum. Both tumors were removed completely. Basing on the results of the clinical examination, of the laboratory data and the histopathological examination of the resected tumors a diagnosis of Castleman's tumor of the plasma-cell type was made. PMID- 1290982 TI - [Sinus histiocytosis with generalized lymphadenopathy--Rosai-Dorfman disease]. AB - A case of sinus histiocytosis with generalized lymphadenopathy--Rosai-Dorfman disease--in a 54 year old male is presented. The diagnosis was made by biopsy of the lymph nodes and histopathological examination of the affected organ. Treatment with prednisone and cyclophosphamide induced clinical improvement. The diseases clinical advanced stage and organ localization and the immunosuppressive therapy resulted in a opportunistic infection--pneumocystidosis and death of the patient within half a year after starting of therapy. PMID- 1290983 TI - [The role of alveolar macrophages in the pathogenesis of destructive lung diseases]. PMID- 1290984 TI - [Magnesium salts in the treatment of bronchial asthma]. PMID- 1290985 TI - [Immunological approach to the evaluation of the activity of the tuberculous process]. AB - The aim of the study was to determine the immunological criteria of the activity of the lung tuberculosis. Some immunological tests based on cellular and humoral immunity were assessed in 3 groups: I--patients with active, bacteriologically confirmed tuberculosis, II--individuals with inactive minimal changes in the lung, III--healthy subjects. We found that among patients with active tuberculosis cellular immunity was depressed: both percentage of T-lymphocytes and their function, usually associated with cutaneous anergy to tuberculin. But the humoral immunity was enhanced. The authors have shown that the people with inactive minimal changes in the lung take place between the patients with active tuberculosis and healthy subjects. PMID- 1290986 TI - [Lung cancer mortality rate in the Upper Silesia 1985-1990]. AB - Mortality rates in the years 1985-1990 in males and females with lung cancer in the Katowice province were analysed. Partial rates according to age groups and "raw" rates were calculated. Basing on these, standardized rates were assessed (related to administrative units: 45 cities and 48 districts). The regions with the highest and lowest risk of mortality due to lung cancer were identified using the isarytmic method and standardized rates. The regions with the highest risk are those with a mortality rate for males of 85 per 100,000 and 13 per 100,000 for females. A statistically significant difference was seen between some regions (p = 0.01). The cohort analysis predicts that in the immediate future, an increase of mortality rates in rat es due to lung cancer can be predicted. Also a very dynamic increase in mortality rates in females can be foreseen. PMID- 1290987 TI - [Ventilatory function of the lungs in galenite ore miners]. AB - The study was carried out on a group of 54 galenite miners (composed of PbS slats) (age 37.9 +/- 7.5 years). The following parameters were assessed: VC, TLC, RV, RV%TLC, FEV1, FEV1%VC, Raw, Gaw, FEF50%, FEF75%. Also the ventilatory homogeneous index was calculated V2:V1 basing on the analysis of the flow volume curve. The control consisted of subjects living in the vicinity of the mine and smelting works. In 3.1% of the miners various stages of increased flow obstruction was found. In 8.3% signs of emphysematous changes, in 23.9% minor disturbances of bronchial resistance. In comparison with the control the miners demonstrated expiratory flow mainly in the small airways. Duration of exposure and co-existent chronic bronchitis increased the above mentioned observations and decreased the homogeneity index. PMID- 1290988 TI - [Prospective epidemiological studies of chronic bronchitis in workers in a coke processing plant]. AB - In 1977 an epidemiological survey was carried out on incidence of chronic bronchitis in 652 workers (age 20-64) of a coking plant. The survey was repeated six years later in 300 of the original participants (56%). The aim of the study was to assess the effect of smoking, age and occupation on incidence of chronic bronchitis and dynamic change of FEV1 values during the six years. During the 6 years the incidence of chronic bronchitis rose from 22% to 43%. Mean annual decrease of FEV1 was higher in smokers as compared to nonsmokers (57.4 versus 52.6 ml per year). Higher mean falls of FEV1 values were noted in subjects with occupational risk factors present (68.4 ml) in comparison with those with low occupational exposure (51.2 ml). Susceptible subjects presented a thrice higher annual FEV1 decrease rate (142 ml). PMID- 1290989 TI - [Chronic bronchitis and ventilatory capacity of the lungs in relation to the function of small airways in workers in a Coke-Processing Plants in Zabrze]. AB - In 449 male workers of the Zabrze Coking Plant (age 18-62 years) a questionnaire analysis of presence of bronchitic symptoms was carried out. The following ventilatory parameters were also assessed: FVC, FEV1, PEF, MEF75, MEF50, MEF25. Chronic bronchitis was diagnosed in 30.5% of the analysed subjects. The incidence of chronic bronchitis was four-fold higher in smoking males (33.9%) in comparison with non-smokers (8.3%). The authors did not find any relation between the character of work in subject with occupational exposure to atmospheric pollutants and incidence of chronic bronchitis. Smoking produced a decrease in flow during forced expiration especially in males older than 40 years. Subjects with higher occupational exposure to atmospheric pollutants demonstrated higher incidence of airway obstruction (21.2%) and lower mean FEV1% and flow volumes in comparison to subjects with lower occupational exposure. PMID- 1290990 TI - [Evaluation of the strength of respiratory muscles in healthy persons]. PMID- 1290991 TI - Bronchoscopy and bronchoalveolar lavage in clinical practice and research- usefulness and potential pitfalls. PMID- 1290992 TI - [Ofloxacin in the treatment of pulmonary changes caused by Mycobacterium avium and Mycobacterium xenopii]. AB - Two cases of atypical mycobacterial infections are reported. The first caused by Mycobacterium avium in a patient with silicosis, the second by Mycobacterium xenopii in a subject with evidence of extensive post-tuberculosis pulmonary lesions. Both were treated with ofloxacin with good results. PMID- 1290993 TI - [Benign neoplasms of the lung]. PMID- 1290994 TI - Meningococcal infections in Quebec--1991-92. PMID- 1290995 TI - Meningococcal disease in Newfoundland, 1967-1991. PMID- 1290997 TI - National Advisory Committee on Immunization (NACI). Revised guidelines for booster vaccination against hepatitis B. PMID- 1290996 TI - Domoic acid intoxication. PMID- 1290998 TI - Screening for intestinal parasites in adopted children from Romania--Quebec. PMID- 1290999 TI - The surveillance challenge: final stages of eradication of poliomyelitis in the Americas. PMID- 1291000 TI - Recent trends in tuberculosis incidence in Canada 1980-90. PMID- 1291001 TI - Revised case definition and reporting forms for tuberculosis (effective 1 January 1990). PMID- 1291003 TI - Influenza virus strain identification for the 1991-92 influenza season. PMID- 1291002 TI - Influenza in Canada, 1990-91 and 1991-92 season. PMID- 1291004 TI - Laboratory reports of human viral and selected non-viral infections in Canada- 1991. PMID- 1291005 TI - Disseminated coccidioidomycosis in a Canadian patient with chronic HIV infection- Ontario. PMID- 1291006 TI - Guidelines for the investigation of individuals who were placed under surveillance for tuberculosis post-landing in Canada. Immigration and Overseas Health Services and the Bureau of Communicable Disease Epidemiology. PMID- 1291007 TI - Guidelines for the identification, investigation and treatment of individuals with concomitant tuberculosis and human immunodeficiency virus infection. Canadian Thoracic Society, the Tuberculosis Directors of Canada and the Department of National Health and Welfare. PMID- 1291008 TI - Outbreak of penicillin- and tetracycline-resistant Neisseria gonorrhoeae in Manitoba in 1991. PMID- 1291009 TI - Cholera associated with international travel, 1992--United States. PMID- 1291010 TI - Canadian influenza serosurvey prior to the 1992-1993 season. PMID- 1291011 TI - Salmonella hadar associated with pet ducklings--United States. PMID- 1291013 TI - Bloodborne pathogens in the health care setting: risk for transmission. PMID- 1291012 TI - National Advisory Committee on Immunization (NACI). Statement on Haemophilus influenzae type B conjugate vaccines for use in infants and children. AB - Currently three Haemophilus influenzae type b (Hib) conjugate vaccines are licensed for use in Canada in infants 2 months of age and older: HibTITER (Lederle Laboratories), PedvaxHIB (Merck Sharp & Dohme Canada) and Act-HIB (Pasteur-Merieux, distributed in Canada by Connaught Laboratories Ltd.). A fourth vaccine, licensed both as a single product (ProHIBIT) or in combination with diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT-Hib) (Connaught), is limited to use in children 18 months of age or older. The following recommendations incorporate those previously published by the National Advisory Committee on Immunization(1), provide information on Act-HIB (which was licensed in March 1992) and summarize recently published data on the comparative immogenic effects and interchangeability of Hib conjugate vaccines (2-6). PMID- 1291014 TI - Adverse events following the administration of hepatitis B vaccines. PMID- 1291015 TI - Control of influenza A outbreaks in nursing homes: amantadine as an adjunct to vaccine, Washington State, 1989-1990--United States. PMID- 1291016 TI - Death from a severe case of Plasmodium falciparum in a Canadian. PMID- 1291017 TI - Gastroenteritis outbreak at an industrial camp--British Columbia. PMID- 1291018 TI - Foodborne hepatitis A outbreaks in California--United States. PMID- 1291019 TI - Dental management of a child with anorexia nervosa who presents with severe tooth erosion. AB - Carbonated soft drinks can, when consumed regularly and in large quantities, cause severe dental erosion. In patients with anorexia nervosa the temptation to substitute these drinks for their regular diet has increased, since they are readily available, relatively cheap and their consumption is socially acceptable. The dental management of a young child suspected of having anorexia, who presented with severe dental erosion, is described. PMID- 1291020 TI - Treatment options for the edentulous mandible. AB - Prosthodontic literature is replete with articles reporting longitudinal studies of, and clinical and laboratory procedures for, dental implants. There is no doubt that implant-borne prostheses are ideal treatment options for some patients; for other, alternatives must be considered. The purpose of this article is to present an overview of the aetiology of mandibular atrophy and to review a broad range of treatment options for patients who have atrophic mandibles. Whilst techniques are listed for completeness and not necessarily out of preference, with epidemiological and demographic trends in mind, the need for preventive prosthodontics is emphasised. PMID- 1291021 TI - Problems associated with restoration of dentitions after orthodontic treatment using anterior tooth space. AB - Three case reports are presented to illustrate some problems associated with restoration of dentitions following orthodontic treatment using anterior tooth space. These include the projecting premaxilla, conversion of lateral incisors to resemble central incisors and excess residual space. PMID- 1291022 TI - Evaluation of impression tray techniques in microstomic patients. AB - Three different methods of constructing impression trays for patients suffering from microstomia have been described. When sectional trays with connectors are designed, proper alignment of the sections is necessary for satisfactory results. Flexible trays, or even silicone putty without a tray, can be used for making preliminary impressions in these cases. PMID- 1291023 TI - Long-term electromyography as a possible diagnostic aid for detecting craniomandibular dysfunctions. AB - As there is a positive correlation between oral parafunctional habits and craniomandibular disorders, objective electromyographic findings on parafunctional jaw activities could be very interesting for the diagnosis and management of craniomandibular disorders. The described pocket-sized and battery operated electromyographic measuring device fulfils the essential requirements for monitoring and recording parafunctional activity in a chosen time period. It is easy to handle and can therefore be operated by a trained patient. At the end of the registration the collected data are transferred to a computer for statistical or graphical analysis. With this device, long-term electromyography on patients in their usual environment is possible. Further studies on parafunctional behaviours applying long-term electromyography could increase the understanding of craniomandibular disorders. PMID- 1291024 TI - The replacement of missing maxillary central incisor teeth incorporating a midline diastema with a fixed-fixed resin-retained bridge. AB - The replacement of maxillary central incisor teeth with the maintenance of a midline diastema can create considerable problems for the restorative dental surgeon. This case report illustrates the treatment of such a case using a fixed fixed resin-retained bridge with a modified palatal connector. Alternative treatment options are discussed. PMID- 1291025 TI - In vitro microleakage of Class V composite resin restorations with and without light-cured glass-ionomer (poly alkenoate) cement lining. AB - The restoration of Class V cavities with composite resin when the cervical cavity margin extends onto the root surface poses a special problem with regard to marginal seal. The use of glass-ionomer (poly alkenoate) cement (GIC) linings has not overcome this problem completely. The efficacy of a new light-cured GIC lining was tested in vitro, as was the use of a modern dentine-bonding agent. The light-cured GIC lining afforded a reliable marginal seal but the efficacy of the dentine-bonding agent related to the time of finishing of the composite restoration. PMID- 1291026 TI - Neurobiology and inflammatory arthritis. AB - As diagrammed in Figures 1 and 2, the central and peripheral nervous systems, the endocrine system, and immune and inflammatory systems are extensively integrated. The boundaries defining these systems are both anatomically and molecularly blurred. This realization has been driven by the ongoing revolution in molecular biology. Normally the deleterious effects of excessive or persistent inflammation are prevented by homeostatic neuroendocrine feedback loops. Conversely, dysfunction in these counter-regulatory responses may lead to important clinical phenomena such as autoimmunity and chronic inflammation in association with behavioral alterations such as fatigue, depressed mood, and loss of libido. Continued research into the neurobiology of inflammation appears likely to explain some of the fundamental abnormalities in diseases such as RA and lead to new, more effective therapies. PMID- 1291027 TI - Office-based arthroscopy. PMID- 1291028 TI - Education in rheumatology. PMID- 1291029 TI - Peripheral and central administration of cocaine produce conditioned odor preferences in the infant rat. AB - To assess the development of the reinforcing properties of cocaine, 3- to 4-day old rat pups were administered cocaine s.c (3.0-30.0 mg/kg), intracerebroventricularly (3.0-10.0 micrograms/injection), or directly to the nucleus accumbens (1-25 micrograms/injection) in the presence of a distinctive odor. Six to 8 h later, pups were allowed a choice between the paired odor and a non-paired odor. Compared to saline treated controls, pups demonstrated a preference for the odor paired with cocaine for each route of administration. Taken together with previous work demonstrating that cocaine increases responding for electrical self-stimulation of the basal forebrain, these results suggest that cocaine is rewarding in the infant animal and that mesolimbic structures may mediate, at least in part, those reinforcing properties. PMID- 1291030 TI - Different thresholds of HSP70 and HSC70 heat shock mRNA induction in post ischemic gerbil brain. AB - Thresholds of induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brain, HSP70 mRNA was little present, while HSC70 mRNA was present in most cell populations. A 0.5-min occlusion of bilateral common carotid arteries did not affect the amount of HSP70 and HSC70 mRNAs. The selective induction of HSC70 mRNA was observed in dentate granule cells at 1 h, and in most cells of hippocampus especially dentate gyrus at 3 h after 1 min of ischemia when induction of HSP70 mRNA was not evident in the identical brain. The selective induction diminished by 2 days. However, after 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal cells from 1 h of the reperfusion, and the co-induction prolonged in CA1 cells until 2 days. Body temperatures monitored at rectum increased after the reperfusion with a peak at 30 min. The degree of increase of the body temperature was significantly higher in the case after 2-min ischemia than in the cases after 0.5- and 1-min ischemia. Although HSP70 and HSC70 mRNAs are generally co-induced in stressful conditions, our results suggest the different thresholds of the induction between HSP70 and HSC70 mRNAs after transient brain ischemia. The selective induction of HSC70 mRNA which is not accompanied by the induction of HSP70 mRNA may relate to the differences of the duration of ischemia and the degree of the increase of body temperature after ischemia. PMID- 1291031 TI - Effect of inhibiting enkephalin catabolism in the VTA on motor activity and extracellular dopamine. AB - The mixed inhibitor of enkephalin catabolism, kelatorphan, was microinjected into the ventral tegmental area (VTA) of rats to determine if endogenous enkephalins can modulate dopamine transmission in the mesoaccumbens projection. The concentration of extracellular dopamine content in the nucleus accumbens was monitored using in vivo microdialysis simultaneously with measuring motor behavior. Kelatorphan microinjection into the VTA produced a dose-related increase in motor activity and extracellular dopamine in the nucleus accumbens. While the change in extracellular dopamine was modest as compared to exogenous stimulation by a mu agonist such as DAMGO, there was a marked increase in the extracellular content of dopamine and serotonin metabolites. This suggests that mesoaccumbens dopamine transmission is under tonic control of endogenous enkephalins at the ventral tegmental area level. PMID- 1291032 TI - Expression of c-fos protein in rat brain after electrical stimulation of the aortic depressor nerve. AB - To reveal central nervous system (CNS) structures involved in the baroreceptor reflex we studied the distribution of Fos protein-like immunoreactivity in the rat brain after one hour of electrical stimulation of the aortic depressor nerve (ADN). In 13 male Wistar rats under urethane the ADN was cut on both sides and the central ends were placed on stimulating electrodes. Intermittent (11 s on, 6 s off) electrical stimulation at parameters set to elicit a drop in mean arterial pressure of 15-30 mmHg was applied to one, both or neither ADNs for 1 h. CNS sections were incubated for 48 h in anti-Fos antibody and prepared for visualization of the reaction product using the ABC immunoperoxidase technique. Label was found in several discrete brain nuclei primarily on the side ipsilateral to the side of stimulation. In the medulla labelled nuclei were found in the nucleus tractus solitarius, area postrema, rostral and caudal ventrolateral medulla, nucleus ambiguus and medullary reticular formation. In the pons labelled neurons were found in the lateral and ventrolateral parabrachial nucleus, locus coeruleus, pontine reticular field and A5 region. In the forebrain labelled nuclei were observed in the peri- and paraventricular hypothalamus, supraoptic nucleus, subfornical organ, preoptic area, central nucleus of the amygdala, median preoptic area, horizontal limb of the diagonal band, bed nucleus of the stria terminalis and islands of Calleja. In control animals moderate amounts of label were present in the supraoptic nucleus and periventricular hypothalamus bilaterally. These results define central pathways involved in mediating the baroreceptor reflex. PMID- 1291033 TI - Characterization of a neurofilament-associated kinase that phosphorylates the middle molecular mass component of chicken neurofilaments. AB - We have examined the properties of a chicken neurofilament (NF) kinase partially purified from NF-enriched preparations. This kinase cosediments with NFs following extraction with Triton X-100 and can be separated in an active form from NFs by treatment with 0.8 M KCl. Sequential chromatography of the salt extract on DEAE-cellulose and phosphocellulose results in an approximately 500 fold increase in specific activity over endogenous NF preparations as measured by 32P-incorporation into the middle molecular mass component of NFs (NF-M). The kinase is Mg(2+)-dependent, second messenger-independent and inhibited by high concentrations of heparin. It shows selectivity for NF-M and evidence is presented that the kinase phosphorylates NF-M solely in the tail domain. The kinase can also phosphorylate the microtubule-associated proteins tau and MAP2 as well as mammalian NF-M, all of which share putative phosphorylation sequences with chicken NF-M. PMID- 1291034 TI - Basic fibroblast growth factor rescues CNS neurons from cell death caused by high oxygen atmosphere in culture. AB - In the present study, we cultured rat CNS neurons and tested the neurotrophic support provided by basic fibroblast growth factor (bFGF) to prevent the oxygen induced neuronal cell death. When rat basal forebrain (septum and vertical limb of diagonal band of Broca) cells of embryonic day 20 were cultured in a serum free medium containing 5 microM cytosine arabinoside in a 50% oxygen atmosphere, the neuronal cells, which were immunostained by an anti-microtubule-associated protein 2 (MAP2) antibody, gradually died after 1 day in culture. After 3.5 days in culture, only 2-5% of neuronal cells survived. This oxygen-induced cell death of cultured basal forebrain neurons was reversed by the addition of bFGF at a concentration of 100 ng/ml. This cell-saving effect was dose-dependent, and the ED50 value was 12 ng/ml. Nerve growth factor (NGF) and insulin-like growth factor II could not prevent cell death. The activity of choline acetyltransferase was also maintained when bFGF was present in the basal forebrain culture. Viable astroglial cells, which were immunostained by an anti-glial fibrillary acidic protein, accounted for a few percent of the total number of cells after 3 days in culture both with and without 100 ng/ml of bFGF. The survival-enhancing effect of bFGF was observed not only in basal forebrain neurons but also in neocortical and hippocampal neurons. However, the sensitivity to oxygen toxicity of cultured neurons from the 3 CNS regions varied greatly. The neocortical neurons were the most sensitive to oxidative stress, while the hippocampal neurons were the most resistant. These results suggest that bFGF plays an important role in saving neuronal cells from oxidative stress during their long life without division. PMID- 1291035 TI - Successful transmission of Creutzfeldt-Jakob disease from human to mouse verified by prion protein accumulation in mouse brains. AB - The accumulation of prion protein (PrP) was revealed in the brains of mice inoculated with the brain homogenate from seven patients with Creutzfeldt-Jakob disease (CJD) by immunohistochemistry using hydrolytic autoclaving. It was not found in the brains of mice inoculated with material from either two patients with Gerstmann-Straussler syndrome or two with other dementing illnesses. PrP accumulation took the forms of diffuse neuropil accumulation in the gray matter and plaque-like accumulation in the white matter and was observed in particular areas in the supratentorial structure. Its distribution was narrower than that in the brains of mice infected with a mouse-adapted CJD strain. PrP accumulation was found not only in all histopathologically positive mice, but also in some histopathologically negative mice. In all groups of mice inoculated with the material from each CJD patient, the percentage of mice with PrP accumulation was equal to or exceeded that of mice with the histopathological findings. PrP immunohistochemistry using formic acid pretreatment stained such plaque-like accumulation less intensely than that using hydrolytic autoclaving and did not stain diffuse neuropil accumulation. Therefore, PrP accumulation which can be revealed in the brains of first-passage CJD mice by this new immunohistochemical method may be the most sensitive hallmark of successful transmission. PMID- 1291036 TI - Histamine-caused itch induces Fos-like immunoreactivity in dorsal horn neurons: effect of morphine pretreatment. AB - It is well known that cutaneous pain causes c-fos gene expression in the dorsal horn neurons. The present study examined whether or not an itching sensation had the same effect on these neurons. In order to produce an itching sensation, cotton balls soaked in histamine solutions of different concentrations were applied to the lower limbs of rats and then the treated area was scratched with the tip of a pair of forceps. After 2 h, the number of neurons showing Fos-like immunoreactivity was significantly increased in a dose-dependent manner in the ipsilateral dorsal horn when compared to saline-treated and scratched controls. When scratching with the forceps was omitted, the number of these neurons was reduced to one-third, but was still significantly higher than in controls treated only with saline. Expression of Fos-like immunoreactivity in these animals was markedly reduced by morphine pretreatment (10 mg/kg, i.p.), suggesting that the transmission of both itch and pain is blocked by morphine. PMID- 1291037 TI - Protein synthesis inhibition blocks maintenance but not induction of epileptogenesis in hippocampal slice. AB - We have been examining the role of protein synthesis in the development and maintenance of spontaneous bursting in the rat hippocampal slice. We used stimulus train induced bursting (STIB) as an in vitro model for epileptogenesis, to study the effects of 3 different protein synthesis inhibitors (cycloheximide, anisomycin, puromycin) on the development of bursting. We report here that none of these inhibitors blocked the induction of bursting, suggesting that protein synthesis is not essential for the development of electrically induced bursting. However, when established spontaneous bursting was examined in the presence of cycloheximide, the duration of the bursting phase was markedly reduced, suggesting that the maintenance of spontaneous bursting in the early hours requires ongoing protein synthesis. PMID- 1291038 TI - Memory dysfunction following disruption of glutamergic systems in the temporal region of the rat: effects of agonistic amino acids. AB - It has previously been shown that disruptions of fiber connections between the temporal cortex (TC) and the lateral entorhinal cortex (LEC) in rats result in severely impaired retention of a simultaneous brightness discrimination task. This memory impairment is accompanied by reduced high affinity D-aspartate uptake in both TC and LEC. The purpose of this study was to investigate whether systemic administration of glutamergic agonists might ameliorate the mnemonic dysfunction seen to follow TC/LEC transections. The results from Experiment 1 show that agonists acting selectively at the NMDA receptors (NMDA and glycine) or the quisqualate receptors (AMPA) produced complete amelioration of the memory deficit. Injection of kainic acid only produced a slight improvement of memory. The results from Experiment 2 show that the positive effects of agonists are probably not attributable to peripheral adrenergic mechanisms, because blockade of sympathetic terminal release did not prevent mitigating effect of glycine. The results are discussed in terms of possible central nervous mechanisms interfered with by the various agonists. PMID- 1291039 TI - Distribution of glycinergic terminals on lumbar motoneurons of the adult cat: an ultrastructural study. AB - The distribution of glycine-like immunoreactivity on cat lumbar motoneurons was examined in electron microscopy, using pre-embedding immunocytochemistry. In the dorsolateral portion of the ventral horn, numerous labeled axon terminals were presynaptic to somatic and dendritic profiles of alpha-motoneurons. Most of the glycinergic boutons contained pleomorphic vesicles and showed symmetrical contacts. On the somatic and proximal dendritic compartments, glycinergic terminals accounted for, respectively, 24.6 and 26.6% of the total number of terminals. There were very few glycinergic terminals on gamma-motoneurons. Immunoreactive axons, dendrites and cell bodies were also observed near the motoneurons. These results support the view that glycine plays a major role in the inhibition of alpha-motoneurons and suggest that inhibitory mechanisms occur on the soma as well as on dendrites. PMID- 1291040 TI - [Pathology of the uterine cervix. Infectious lesions of the endocervix and exocervix]. AB - Bioptic findings from the region of the endo- and exocervix of the uterus were analyzed in a retrospective study covering the years 1988-1990. The series studied consisted of 366 women. Infectious processes in the cervix were evaluated in this first part of the study. Over the period investigated, 155 cases of cervicitis were established. Of these 56 (36.2 %) were acute bacterial, 17 (10.9 %) were lympho-plasmocytic (chlamydial), and 4 (2.5 %) were herpetic. The largest group of 78 (50.3 %) patients had HPV induced lesions. Koilocytic dysplasia was grouped into three grades according to severity. Mild dysplasia occurred in 16 patients (22 %), intermediate in 19 patients (26 %) and severe dysplasia in 37 patients (52 %). (Fig. 6, Ref. 15.). PMID- 1291041 TI - [Adverse effects of antidepressive agents in hospitalized geriatric patients]. AB - The frequency, intensity and profile of adverse effects of antidepressants was studied in elderly patients. The series consisted of 102 patients with depression admitted to hospitals in Bratislava and Moscow. The adverse effects of amitriptyline (Amitriptylin Spofa) and maprotiline (Ludiomil Ciba-Geigy) were compared. The assessment done on days 0, 7, and 28 of treatment showed that xerostomia had the highest occurrence rate with both preparations studied. In patients treated with amitriptyline adverse effects were more severe and were recorded more frequently, requiring treatment withdrawal in 3 patients. The overall intensity of adverse effects was significantly higher with amitriptyline (p < 0.05). In the group of patients treated with amitriptyline the adverse effects were more marked in those with severe somatic pathology. The risk of amitriptyline treatment in elderly patients is being emphasized along with the need for monitoring and correcting adverse effects of the treatment. Although maprotiline exhibited a lower occurrence rate of adverse effects, cardiac functions should be regularly checked in patients with preexisting cardiac pathology. (Tab. 2, Fig. 3, Ref. 6.). PMID- 1291042 TI - [A screening program for the diagnosis of early forms of prostatic carcinoma]. AB - Carcinoma of the prostate is at present one of the most frequently occurring malignancies in the male population. The disease can be cured only at the early stage when it has not yet spread beyond the limits of the gland. Early, clinically asymptomatic forms of carcinoma of the prostate can be diagnosed only by screening examinations of men. The justification of screening has, however, not been conclusively established and the fear of damaging the patient on examination could not be dispelled. The project of an international co-operative study was accepted in Stockholm in 1990 with the aim to address this question. The Department of Urology of Derer's Hospital with Policlinic, along with several urological, oncological, and research departments, have decided to join the project in order to contribute to the improvement of diagnosis and treatment of carcinoma of the prostate. (Fig. 1, Ref. 12.). PMID- 1291043 TI - [Comparison of the effect of nifedipine and verapamil on lipid metabolism in experimental atherosclerosis in rabbits]. AB - The aim of the work was to study the effect of 8-week treatment with two calcium channel blockers on some parameters of lipid metabolism in rabbits. Experimental atherosclerosis was induced by 1% cholesterol diet. The calcium channel blockers were administered twice daily in the following doses: nifedipine 1.0 mg.kg-1 and verapamil 2.0 mg/kg-1 x day-1. The treatment with calcium channel blockers enhanced the level of total cholesterol as well as of triglycerides and decreased the HDL: total cholesterol ratio in all the experimental groups. The changes induced by nifedipine were, however, less significant compared to the effect of verapamil. The absolute amount of fatty acids determined by gas chromatography was lower after nifedipine administration in comparison to the verapamil treated group. Nifedipine induced a more favorable proportion in the composition of fatty acids. The increase in the level of monounsaturated fatty acids (palmitoleic and oleic acid) as well as the decrease in the level of polyunsaturated fatty acids (especially linoleic acid) was the lowest in the nifedipine treated group. (Fig. 6, Ref. 30.). PMID- 1291044 TI - [The effect of verapamil and nifedipine on acid-base and electrolyte disorders induced by cholesterol in rabbits]. AB - The influence of cholesterol atherogenic diet on the acid-base balance and electrolyte profile was investigated in rabbit blood and the effect of simultaneous administration of verapamil and nifedipine on the induced changes was evaluated. Cholesterol diet resulted in significant metabolic acidosis, hyperkalemia, and a slight decrease in plasma ionized calcium. On the other hand, longterm treatment with verapamil and nifedipine exhibited their protective effect, with the acid-base status and electrolyte profile maintained within the normal range. The protective effect of verapamil and nifedipine against cholesterol induced acid-base and electrolyte disturbances appears to be associated with their antiatherogenic activity. (Fig. 5, Ref. 10.). PMID- 1291045 TI - Two-dimensional poly(acrylamide) electrophoresis of fluoresceinated glycopeptides. Resolution and structural characterization of ovalbumin glycans. AB - The microheterogeneous mixture of fluoresceinated glycopeptides (FGPs) obtained from the single site of glycosylation of chicken ovalbumin was resolved by a combination of discontinuous electrophoresis in a high-density poly(acrylamide) gel (PAGE) for sizing, in conjunction with borate-PAGE. Two FGPs of similar size but with different mobilities in borate-PAGE were purified and characterized by sequential exoglycosidase digestion and sizing on the discontinuous PAGE system, as well as by methylation analysis. The two FGPs of identical size are distinct and have structures beta-D-Glc pNAc-(1-->2)-alpha-D-Man p-(1-->3)-[beta-D-Glc pNAc-(1-->4)]-[beta-D-Glc pNAc-(1-->2)-alpha-D- Man p-(1-->6)]-beta-D-Man-p-(1- >4)-beta-D-Glc pNAc-(1-->4)-beta-D-Glc pNAc-1-->R and alpha-D-Man p-(1-->2)-alpha D-Man p-(1-->3 or 6)-[alpha-D-Man p-(1-->3)-[alpha-D-Man p-(1-->6)]-alpha-D-Man p (1-->6 or 3)]-beta-D-Man p-(1-->4)-beta-D-Glc pNAc-(1-->4)-beta-D-Glc pNAc-1-->R (R = Asn-(amino acids)-fluorescein). The results demonstrate that two-dimensional PAGE is applicable to the separation and characterization of complex mixtures of FGPs. The procedure is rapid, sensitive, and convenient for glycopeptide mapping, and for the purification and structural characterization of glycans. Furthermore, the FGPs can be characterized with affinity matrices, such as lectins, and by methylation analysis. PMID- 1291046 TI - Regioselectivity in the sulfation of some chemically-modified heparins, and observations on their cation-binding characteristics. AB - Two modified forms of heparin, polymers A and B, have been prepared, one containing residues of nonsulfated alpha-L-idopyranosyluronic acid (3) and the other residues of alpha-L-galactopyranosyluronic acid (7), in place of the normal alpha-L-idopyranosyluronic acid 2-sulfate (1). In addition, both A and B contained 2-acetamido-2-deoxy-alpha-D-glucopyranosyl 6-sulfate residues (6) in place of the corresponding N-sulfated residues (2) of the original heparin. These polymers were subjected to sulfation under various conditions. Examination of the products by NMR spectroscopy showed that polymer A was sulfated initially at position-3 of residue 3, and that slower substitution occurred at position-3 of 6. By contrast, polymer B exhibited low regioselectivity, as sulfation occurred with about equal facility at positions-2 and -3 of 7, and -3 of 6. The sulfation products had no significant anti Xa activity. Based on the paramagnetic effects of Cu2+ and chemical shift displacements induced by Ca2+, NMR spectroscopy was used to compare cation-binding properties of A and B with those of heparin. In contrast to heparin, which forms a complex with Cu2+ detectable at a level of < 10(-3) mol per dimeric unit of the polymer, neither A nor B exhibited an interaction with the cation. However, polymer A was found to bind Ca2+, in this respect being distinct from the related modification, 1-->6, which contains a 2 sulfate group in 1, as well as from polymer B. PMID- 1291047 TI - Structural analysis of the carbohydrate chains isolated from mistletoe (Viscum album) lectin I. AB - Two glycopeptide fractions prepared from mistletoe (Viscum album) lectin I by Pronase digestion were fractioned by affinity chromatography on a concanavalin A Sepharose column. With 400-MHz 1H NMR spectroscopy, in conjunction with sugar analysis, the following oligosaccharide structures could be determined: two oligomannose-type glycans in the ratio 4:1, one containing six mannose and the other containing five mannose units, both with two 2-acetamido-2-deoxyglucose units. In addition, a mannotriosyl-->N,N'-diacetylchitobiose glycan containing a xylosyl group and an alpha-fucosyl group (1-->3)-linked to the 2-acetamido-2 deoxyglycosyl-1 residue, a common core element of many plant glycoproteins, was also observed. PMID- 1291048 TI - The structure of the sialic acid-containing Escherichia coli O104 O-specific polysaccharide and its linkage to the core region in lipopolysaccharide. AB - Mild acid hydrolysis of Escherichia coli O104 lipopolysaccharide released an O specific polysaccharide, a tetrasaccharide repeating unit, the corresponding dimer, and a disaccharide fragment of the repeating unit. Complete and incomplete cores, and oligosaccharides comprising fragments of the repeating unit and the core region, were also obtained. On the basis of sugar and methylation analysis, FAB-mass spectrometry and NMR spectroscopy of the hydrolysis products, the repeating unit of the O-specific polysaccharide was shown to be the tetrasaccharide:-->4)-alpha-D-Galp-(1-->4)-alpha-Neup5,7,9Ac3++ +-(2-->3)-beta-D- Galp-(1-->3)-beta-D-GalpNAc (1-->. The linkage between the O-specific polysaccharide chain and the core region, which appeared to be of the R2 type, was established. These results indicate that N-acetylneuraminic acid, located in the O-specific polysaccharide, is an inherent lipopolysaccharide component. PMID- 1291049 TI - In vitro biosynthesis of GbOse4Cer (globoside) and GM2 ganglioside by the (1-->3) and (1-->4)-N-acetyl beta-D-galactosaminyltransferases from embryonic chicken brain. Solubilization, purification, and characterization of the transferases. AB - (1-->4)-N-Acetyl-beta-D-galactosaminyltransferase (GalNAcT-1) and (1-->3)-N acetyl-beta-D-galactosaminyltransferase (GalNAcT-2), which are involved in the in vitro biosynthesis of GM2 and GbOse4Cer glycosphingolipids, respectively, have been solubilized and separated by differential detergent extraction from a membrane preparation of 19-day-old embryonic chicken brain. The separated GalNAcT 1 activity had a pH optima of 7.8-8.0, and the separated GalNAcT-2 activity a single pH optimum of 7.2. Furthermore, the partially purified GalNAcT-2 preparation catalyzed the transfer of N-acetylgalactosamine from UDP-D-[3H]GalNAc to only GbOse3Cer and nLcOse5Cer. Both GalNAcT-1 and GalNAcT-2 activities were purified to approximately 316- and 428-fold, respectively, by use of UDP hexanolamine-Sepharose 4B affinity-column chromatography. However, the partially purified GalNAcT-1 preparation appeared to be active only with GM3, lactosylceramide, and lactotriaosylceramide. The proposed linkage of the N acetylgalactosamine unit incorporated into GM3 is beta-D-GalpNAc-(1-->4)-GM3 from the isolation of [3H]threitol after hydrolysis of the desialylated, lead tetraacetate-treated, enzymic product, beta-D-GalpNAc-(1-->4)-beta-D-[6-3H]Galp (1-->4)-beta-D-Glcp-(1-->1)-Cer . In addition, beta-D-GalpNAc-(1-->3)-GbOse3Cer was produced, as shown by the identification of 2,4,6-tri-O-methyl-galactose after permethylation and hydrolysis of the GalNAcT-2 enzymic product, GalpNAc-[6 3H]Galp--->Gal-->Glc-->Cer. PMID- 1291050 TI - Immunochemical studies on the combining site of the A + N blood type specific Moluccella laevis lectin. AB - The specificity of the anti A+N lectin of Moluccella laevis (MLL) was examined by hemagglutination experiments with enzyme-modified human erythrocytes and by inhibition of hemagglutination. In addition, binding to various glycoproteins and inhibition by different sugars and glycoproteins were examined by enzyme immunoassay with antibodies to the lectin. Treatment of AMM erythrocytes with proteolytic enzymes increased their agglutinability by MLL 4-16-fold; similar treatment of ONN cells decreased their agglutinability 8-16-fold. This is in line with the known location and enzyme sensitivity of A and N specificity determinants. Treatment of the erythrocytes with sialidase increased their agglutinability and abolished the distinction between N and M cells. Hapten inhibition of hemagglutination of AMM and ONN erythrocytes by the lectin, and its binding to glycoproteins measured by enzyme immunoassay, confirmed the high specificity of MLL for N-acetyl-D-galactosamine (200-500 times more than for D galactose) and suggested the presence of hydrophobic interactions around HO-2 of the D-galactose unit. The methyl alpha-glycosides of D-galactose and of N-acetyl D-galactosamine were better inhibitors than the corresponding beta-glycosides; this preference was abolished, and sometimes reversed, when the p-nitrophenyl glycosides of the same monosaccharides were tested, stressing again the importance of hydrophobic interactions in the binding of carbohydrates to MLL. The lectin reacted well with ONN substance and with glycophorin A of the N phenotype (GPAN), but did not react with OMM substance or GPAM. The strongest inhibitor was asialo ovine submaxillary mucin, which contains many unsubstituted alpha-D-GalpNAc-(1-->3)-Ser/Thr residues; calculated per N-acetyl-D-galactosamine residue, it was 1500 stronger than free N-acetyl-D-galactosamine. In accordance with this result, it was found that the lectin strongly agglutinates Tn cells. The specificity of MLL can, thus, be defined as anti-Tn, crossreactive with blood types A and N, and with sialosyl-Tn. The N-specificity can best be explained by assuming that GPAN contains a small number of unsubstituted or partially sialylated alpha-D-GalpNAc-(1-->3)-Ser/Thr residues, which are present in smaller proportions, if at all, in GPAM. PMID- 1291051 TI - Patterns of alpha-L-fucosidase in acute myeloid leukemia cells. Comparison with promyelocytic HL-60 cell line. AB - Changes were observed in alpha-L-fucosidase forms in cells from acute myelocytic leukemias (AML). Total alpha-L-fucosidase activity was not significantly different for normal granulocytes and leukemic cells, but enzymic profiles obtained by chromatofocusing are quite different. In granulocyte profile, two main peaks are present (B and more acidic A) which were eluted at pH 5.2 with a shoulder at pH 4.6. In AMLs the B form is present but weakly expressed, whereas the more acidic forms are the major ones. This pattern may be related either to the malignancy character or to the stage at which the differentiation is stopped. Experiments on an HL-60 cell line (promyelocytic cells corresponding to the AML 3 type) showed that differentiation induced by dimethyl sulfoxide leads to the appearance of the B form present in normal mature cells. Thus the repartition of the enzyme forms seems to be related to the stage of differentiation of the myelocytic cells. PMID- 1291052 TI - Control of glycoprotein synthesis. Characterization of (1-->4)-N-acetyl-beta-D glucosaminyltransferases acting on the alpha-D-(1-->3)- and alpha-D-(1-->6) linked arms of N-linked oligosaccharides. AB - Hen oviduct membranes contain at least three N-acetyl-beta-D glucosaminyltransferases (GlcNAc-T) that attach a beta GlcNAc residue in (1-4) linkage to a D-Man p residue of the N-linked oligosaccharide core, i.e., (1-->4) beta-D-GlcNAc-T III which adds a "bisecting" GlcNAc group to form the beta-D GlcpNAc-(1-->4)-beta-D-Man p-(1-->4)-D-GlcNAc moiety; (1-->2)-beta-D-GlcNAc-T IV which adds a GlcNAc group to the (1-->3)-alpha-D-Man arm to form the beta-D GlcpNAc-(1-->4)-[beta-D- GlcpNAc-(1-->2)]-alpha-D-Man p-(1-->3)-beta-D-Man p-(1- >4)-D-GlcpNAc component; and (1-->4)-beta-D-GlcNAc-T VI which adds a GlcNAc group to the alpha-D-Man p residue of beta-D-GlcpNAc-(1-->6)-[beta-D-GlcpNAc- (1-->2)] alpha-D-Man p-R to form beta-D-GlcpNAc-(1-->6)-[beta-D-GlcpNAc-(1-->4)]-[beta-D GlcpNAc- (1-->2)]-alpha-D-Man p-R. We now report a novel (1-->4)-beta-D-GlcNAc-T activity (GlcNAc-T VI') in hen oviduct membranes that transfers GlcNAc to beta-D GlcpNAc-(1-->2)-alpha-D-Man p-(1-->6)-beta-D-Man p-R to form beta-D-GlcpNAc-(1- >4)-[beta-D-GlcpNAc-(1-->2)]-alpha-D-Man p-(1-->6)- beta-D-Man p-R. The structure of the enzyme product was confirmed by 1H NMR spectroscopy, FAB-mass spectrometry and methylation analysis. Previous work with GlcNAc-T IV was carried out with biantennary substrates; we now show that hen oviduct membrane GlcNAc-T IV can also transfer GlcNAc to monoantennary beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->3) beta-D-Man p-R to form beta-D-GlcpNAc-(1-->4)-[beta-D-GlcpNAc-(1-->2)]-alpha-D Man p- (1-->3)-beta-D-Man p-R. The findings that GlcNAc-T VI' and IV have similar kinetic characteristics and that hen oviduct membranes can convert methyl beta-D GlcpNAc-(1-->2)-alpha-D-Man p to methyl beta-D-GlcpNAc-(1-->4)-[beta-D-GlcpNAc-(1 ->2)]-alpha-D-Man p suggest that these two activities may be due to the same enzyme. The R-group of the beta-D-GlcpNAc-(1-->2)-alpha-D-Man p-(1-->6)-beta-D Man p (or Glcp)-R substrate has an important influence on GlcNAc-T VI' enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1291053 TI - Use of compounds naturally labeled with stable isotopes for the study of the metabolism of glycoprotein neutral sugars by gas-liquid chromatography-isotope ratio mass spectrometry. Technical validation in the rat. AB - In order to develop an alternative method to radioactive labeling for the study of the glycoprotein sugar metabolism in man, the possible use of stable isotopes provided by naturally, 13C-enriched dietary compounds has been explored in rat intestine and serum. Rats were fed a semisynthetic diet containing 67% wheat starch (containing 1.08692 13C atom/100 carbon atoms) for a week, and then the same diet containing corn starch (1.10042% 13C) for a week. Neutral sugars were prepared from delipidated, trichloroacetic acid-precipitable material from 200 400 mg of intestinal mucosa or 1 mL of serum, separated, and analyzed as alditol acetates by gas-liquid chromatography coupled to isotope-ratio mass spectrometry. This technique allowed the determination, in a single experiment, of the amount and 13C abundance of six neutral sugars (including xylose used as internal standard). Despite the low abundance of 13C in natural products, the sensitivity of the technique was found to be sufficient to detect isotopic enrichment as low as 0.001% with good accuracy and reproducibility in 2 micrograms of each glycoprotein neutral sugar. As an example, the pattern of labeling by dietary D glucose from corn starch appears to be very different for fucose, ribose, mannose, galactose, and glucose of intestine or serum macromolecules. PMID- 1291054 TI - Monoclonal antibody to amphomycin. A tool to study the topography of dolichol monophosphate in the membrane. AB - Understanding the topographical orientation of dolichol monophosphate (Dol-P) in the membrane of the endoplasmic reticulum (ER) is of utmost importance for studying the regulation of asparagine-linked protein glycosylation in eukaryotic cells. This was practically impossible due to the nonavailability of a suitable probe. Recent studies on the specific interaction between a lipopeptide, amphomycin, and Dol-P, provided an insight to develop a monospecific antibody to amphomycin which could recognize the amphomycin-Dol-P complex in order to detect Dol-P immunocytochemically in the ER membrane. We report herein the successful production of a monoclonal antibody to amphomycin. The antibody belongs to the IgG+IgM subclasses and is specific for amphomycin when analyzed by the enzyme linked immunoassay and immunoblot procedures. The antibody recognizes with equal potency both the native amphomycin and also mild acid-hydrolyzed amphomycin from which N-terminal fatty acylated aspartic acid has been removed. Preincubation of amphomycin with the antibody partially reduced the inhibitory action of amphomycin on dolichol phosphate mannosyltransferase (EC 2.4.1.83). Furthermore, exposure of capillary endothelial cells to amphomycin, followed by the monoclonal antibody to amphomycin, followed sequentially by staining with FITC-conjugated goat anti-mouse IgG and examination under a fluorescent microscope gives intense fluorescence at the perinuclear region of the cell with a structure reminiscent of the ER. PMID- 1291055 TI - Application of laser photo-CIDNP for an intact glycoprotein in solution. PMID- 1291056 TI - Identification of a new ganglioside from the starfish Asterias rubens. PMID- 1291057 TI - A practical synthesis of 2-O-substituted beta-D-galactopyranosyl (1-->4) linked di- and tri-saccharides as specific acceptors for (1-->3)-alpha-L fucosyltransferase. PMID- 1291058 TI - Galactosylation of non-natural glycosides with human beta-D-galactosyltransferase on a preparative scale. PMID- 1291059 TI - Structure of the O-specific polysaccharide chain of Klebsiella pneumoniae O1K2 (NCTC 5055) lipopolysaccharide. A complementary elucidation. PMID- 1291060 TI - Structure of beta-D-glucans from Fusarium oxysporum. PMID- 1291061 TI - Production of monoclonal antibodies against oligosaccharides coupled to protein. PMID- 1291062 TI - [Synthesis of modified oligosaccharides of the N-glycoprotein as substrate for N acetylglucosaminyltransferase I]. AB - In the synthesis of modified derivatives of octyl O-(alpha-D-mannopyranosyl)-(1- >3)-O-[(alpha-D-mannopyranosyl)-(1-->6)]- beta-D-mannopyranoside, 4.,5 epoxypentyl, a 4-diazirinopentyl, and a 5-(iodoacetamido)pentyl group were attached to the 3''-OH of the trisaccharide. The diazirino derivative may be especially suitable for photolabeling of the active site of N acetylglucosaminyltransferase I (GlcNAcT-I). In addition, the 2'-OH group of the above-mentioned trisaccharide was reduced to a 2'-deoxy group and substituted 2' O-methyl group. PMID- 1291063 TI - Glycosylation using a one-electron-transfer, homogeneous reagent. Application to an efficient synthesis of the trimannosyl core of N-glycosylproteins. AB - Double glycosylation of methyl 2,4-di-O-benzyl-beta-D-mannopyranoside with ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-alpha-D-mannopyranoside using as promoter tris(4-bromophenyl)ammoniumyl hexachloroantimonate, a stable, commercial, and crystalline radical cation, afforded after debenzoylation methyl 2,4-di-O-benzyl 3,6-di-O-(3,4,6-tri-O-benzyl-alpha-D-mannopyranoside in excellent yield. Other mannosyl donors were also investigated. PMID- 1291064 TI - Relationship between the content of [14C]glucose-derived monosaccharides in glycoprotein oligosaccharide chains and the state of enterocytic differentiation of HT-29 cells. AB - The HT-29 cell line derived from a human colon adenocarcinoma has a glucose dependent state of differentiation which is negatively correlated with the presence of D-glucose in the culture medium. The contribution of glucose to the biosynthesis of N-glycan chains, as a function of the differentiation state of HT 29 cells, was shown by: (a) [14C]glucose incorporation by undifferentiated HT-29 cells being lower after 2 h and higher after 19 h of metabolic labeling than that by differentiated cells; (b) a lack of glucose in the culture medium of undifferentiated HT-29 cells diminishing [14C]glucose incorporation into glycan chains, but not changing the glucose distribution between lipid- and protein linked saccharides; (c) glucose behavior in undifferentiated HT-29 cells being not related to mannose-glycan metabolism, as the high-mannose compounds labeled with glucose and observed by HPLC showing a different distribution associated with the duration of glucose labeling; and (d) glucose being interconverted into other monosaccharide-glycan constituents in proportions different in differentiated and undifferentiated cell populations. PMID- 1291065 TI - Resorption of tooth substance: diagnosis and management. PMID- 1291066 TI - The use of synthetic bone materials in dentistry. PMID- 1291067 TI - Dental management of the bone marrow transplant patient. PMID- 1291069 TI - Electronic spreadsheets. Part 2. Appointment management and exploring spreadsheet power. PMID- 1291068 TI - A practical barrier technique for infection control in dental radiology. PMID- 1291070 TI - An evaluation of a one-visit technique for the fabrication of a soft gingival stent. PMID- 1291071 TI - Computerized image analysis in dentistry: present status and future applications. PMID- 1291072 TI - Diagnostic anesthesia for referred trigeminal pain: Part 2. PMID- 1291073 TI - The latest techniques are not always new: a look back at early inventions and innovations in dentistry. PMID- 1291074 TI - Introduction to the special issue on potassium channels. PMID- 1291075 TI - Spotlight on potassium channels and their modulation. PMID- 1291076 TI - Role of ATP dependent potassium channels in myocardial ischaemia. AB - Recently, a class of potassium (K) channels has been discovered which are regulated by the intracellular level of ATP. These channels have been termed ATP dependent K channels (KATP) and have been found to exist in the heart, skeletal muscle, pancreatic beta cells, brain, and smooth muscle. In this article, we discuss the function of the KATP channel in the ischaemic myocardium and present evidence to suggest that activation of these channels may, on the one hand, result in a marked cardioprotective effect from reversible or irreversible electrical, functional or biochemical damage or, on the other hand, have the potential to produce electrical instability and a proarrhythmic effect. The therapeutic potential of potassium channel modulators is also discussed. PMID- 1291077 TI - Modulation of ATP sensitive potassium channels. PMID- 1291078 TI - Role of potassium channels in cycle length dependent regulation of action potential duration in mammalian cardiac Purkinje and ventricular muscle fibres. AB - This review examines the putative role played by three repolarising potassium currents, namely the transient outward current (ito), the inward rectifying current (iK1), and the late outward rectifying current (iK), in the regulation of action potential duration in cardiac Purkinje and ventricular muscle fibres under normal physiological conditions. The role of other potassium currents, including the ATP activated current (iK,ATP) under these conditions is uncertain. Personal experiences and work of others are reviewed to summarise: (1) regulation of normal cycle length dependent action potential duration: (2) the characteristics of ito, iK1, and iK pertinent to repolarisation; and (3) the effects of potassium channel blockers and activators on cycle length dependent action potential duration. The presence of ito creates a notch after depolarisation and limits action potential duration at long cycles. Block of iK1 prolongs action potential duration predominantly by slowing phase 3 of the action potential. Block of iK prolongs the duration predominantly by lengthening phase 2 of the action potential, and the lengthening becomes more pronounced at longer cycles. Activation of iK,ATP shortens the duration, and the shortening becomes more pronounced at longer cycles. Each of the three major repolarising potassium currents appears to play a different role in modulating the action potential duration. Ito creates a notch which resets the early course of plateau, and also limits the duration at long cycles. IK1 contributes to maintenance of plateau and controls repolarisation course during phase 3 of the action potential. IK plays major role in controlling action potential duration within a wide range of cycle lengths in Purkinje fibres, and when present, also in ventricular muscle fibres. PMID- 1291079 TI - Influence of KATP channel modulation on net potassium efflux from ischaemic mammalian cardiac tissue. AB - OBJECTIVE: The aim was to investigate the effect of pre-exposure to inhibitors or activators of the ATP regulated K+ (KATP) channels on the ischaemia induced early changes of the extracellular K+ concentration, the extracellular pH, and the action potential in mammalian cardiac tissue. METHODS: An in vitro model simulating ischaemia was applied to isolated guinea pig papillary muscles while simultaneous microelectrode measurements of the transmembrane potentials and of the pH and K+ activity at the surface of the preparation (pHs and asK respectively) were made. RESULTS: During conditions of superfusion arrest, when accumulation of metabolic acids causes acidification of pHs, the simultaneous development of a true hypoxic state of the muscle is required in order to induce shortening of the action potential duration and accumulation of extracellular K+ with associated membrane depolarisation. Glibenclamide (10-50 microM) slowed the decrease of the action potential duration in 50% of the muscles, while the increase of asK was only moderately (approximately 20%) influenced. In the presence of 200 microM of the KATP channel inhibitor, the mean K+ accumulation was not significantly different from the control. The presence of tolbutamide (1 mM) had no effect on the decrease of action potential duration, but moderately slowed the increase of asK. Superfusion with lemakalim (BRL 38227) decreased action potential duration dose dependently. In papillary muscles in which action potential duration was shortened to approximately 60% of the control duration by presuperfusion with lemakalim, a subsequent ischaemic episode did not increase but rather delayed the rise in asK. During simulated ischaemia in the presence of Ba2+ ions (1 mM), asK showed a transient decrease followed by a rise at a rate similar to that in the absence of Ba2+. CONCLUSIONS: Early ischaemic K+ accumulation and surface acidification are relatively insensitive to KATP channel inhibition or activation prior to the ischaemic insult. The rather loose coupling of the increase of asK and the decrease of action potential duration, as well as the limited effect of sulphonylureas on the K+ increase, suggests that mechanisms other than KATP channel opening could possibly contribute to the initial phase of ischaemic K+ accumulation. PMID- 1291080 TI - Effects of diltiazem and noradrenaline on extracellular potassium changes in the globally ischaemic rat heart. AB - OBJECTIVE: The aim was to investigate the effects of a calcium antagonist (diltiazem) and a catecholamine (noradrenaline) on extracellular potassium accumulation during global ischaemia. METHODS: Extracellular potassium concentration ([K+]e) was measured during 30 min global ischaemia in the isolated rat heart using a valinomycin potassium sensitive electrode. Contracture development during ischaemia was measured throughout with an intraventricular balloon inserted into the left ventricle and myocardial adenine nucleotides were measured in separate series of hearts. RESULTS: In control hearts, [K+]e showed a characteristic triphasic change during 30 min global ischaemia. This consisted of an early rising phase followed by a transient falling phase after the initial peak of [K+]e, and then a late rising phase. Diltiazem suppressed the rate of rise of [K+]e during early ischaemia, but extended the time course of the early [K+]e rise with the higher dose, abolishing the transient falling phase of [K+]e. During late ischaemia, the rise in [K+]e was attenuated by diltiazem. Noradrenaline also suppressed the early extracellular potassium accumulation, but in contrast to diltiazem, hastened the time course of the late [K+]e rise. CONCLUSIONS: Although diltiazem suppresses the early potassium loss during ischaemia as previously described, the drug also decreases the [K+]e fall by some as yet unknown mechanism, so that the [K+]e level becomes higher than control during the falling phase. PMID- 1291081 TI - Effects of intracoronary cromakalim on postischaemic contractile function and action potential duration. AB - OBJECTIVE: The effects of intracoronary cromakalim (1 microgram.kg-1 x min-1) on postischaemic contractile function and monophasic action potential duration at the 95% repolarisation level (APD95) were assessed in a canine model of stunned myocardium. METHODS: Animals (n = 24) were anaesthetised, subjected to a left thoracotomy, and the left anterior descending coronary artery was isolated. Measurements of segmental shortening and monophasic action potential were taken before drug, after drug, during a 15 min occlusion, and at times following reperfusion. RESULTS: Cromakalim significantly improved reperfusion recovery of function. Both preischaemic and postischaemic myocardial blood flows were increased with cromakalim, although there was no significant change in collateral blood flow during ischaemia relative to vehicle. In the absence of ischaemia, cromakalim reduced APD95 by 8%. There was no change in APD95 with vehicle alone. During coronary occlusion, cromakalim significantly reduced APD95 by 27% as compared with 8% in the vehicle group. APD95 values returned to preocclusion levels within minutes of reperfusion and remained there throughout reperfusion (30 min). Glyburide (3.0 mg.kg-1 intravenously), a blocker of ATP sensitive potassium channels, abolished the APD95 effects of cromakalim. One out of six animals given glyburide survived through reperfusion. In contrast, four out of five of the glyburide+cromakalim treated animals survived through reperfusion. CONCLUSIONS: Cardioprotection with cromakalim is likely to be mediated through activation of ATP sensitive potassium channels, measured as a decrease in action potential duration. Shortening of action potential duration with cromakalim was shown to be augmented in the presence of ischaemia. It is suggested that a possible interrelationship between cardioprotection and action potential duration shortening may exist such that the cardioprotective effects of cromakalim may be selective for ischaemic conditions. PMID- 1291082 TI - Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate. AB - OBJECTIVE: The aims were: (1) to determine if a new ischaemia selective ATP dependent potassium (KATP) channel antagonist, sodium 5-hydroxydecanoate (5-HD), blocks ischaemic preconditioning in dogs; (2) to determine whether a small intracoronary dose of glibenclamide, a classical sulphonylurea KATP channel antagonist, could block ischaemic preconditioning independent of systemic metabolic effects. METHODS: Barbitone anaesthetised dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 5 h of reperfusion. Preconditioning was produced by a single 5 min left circumflex occlusion followed by 10 min of reperfusion prior to the 60 min occlusion period. 5-HD (150 micrograms.kg-1 x min-1) or vehicle was given by intracoronary infusion into the ischaemic region over 20 min, beginning 15 min prior to the 60 min occlusion period in the presence or absence of preconditioning. Glibenclamide (3 micrograms.kg-1 x min-1) was given by intracoronary infusion into the left circumflex artery during the 5 min preconditioning period or during the first 5 min of occlusion in preconditioned or non-preconditioned dogs. Transmural myocardial blood flow was measured by radioactive microspheres and infarct size determined by triphenyltetrazolium staining and expressed as a percent of the area at risk. RESULTS: There were no differences in haemodynamic variables, myocardial blood flow, area at risk, or blood glucose between groups. Infarct size was markedly reduced in preconditioned dogs compared to control animals, at 7(SEM 2)% v 29(4)%, p < 0.05 The reduction in infarct size by preconditioning was blocked completely by intracoronary 5-HD, or by intracoronary glibenclamide given during preconditioning or during the first 5 min of the prolonged occlusion period. Neither 5-HD nor glibenclamide affected infarct size in the absence of preconditioning at the doses studied. CONCLUSIONS: These results further strengthen the hypothesis that activation of myocardial KATP channels is involved in the mechanism of ischaemic preconditioning in dogs. PMID- 1291083 TI - Effects of potassium channel modulation during global ischaemia in isolated rat heart with and without cardioplegia. AB - OBJECTIVE: The opening of potassium (K+) channels during regional ischaemia may, by inducing rapid contractile arrest, be an intrinsic energy sparing mechanism. Thus K+ channel openers (for example, lemakalim) exert significant anti-ischaemic effects, whereas glibenclamide exacerbates ischaemic contracture and limits postischaemic functional recovery. The aim of the study was to investigate the ability of these compounds to influence ischaemic injury when used either alone or in combination with rapid arrest induced by a high K+ cardioplegic solution. METHODS: Contractile function of isolated Langendorff perfused rat hearts was assessed using an intraventricular balloon. Hearts were subjected to normothermic global ischaemia (20 min) or cardioplegic arrest (35 min) with and without glibenclamide or lemakalim. Lemakalim (10 mumol.litre-1) or glibenclamide (10 mumol.litre-1) was given, in the presence or absence of cardioplegia, for 2 min immediately prior to the onset of ischaemia. The rate of ischaemia induced contractile failure, the severity of ischaemic contracture, and the degree of postischaemic functional recovery were all measured. RESULTS: In the absence of cardioplegia, the time to contractile arrest in control hearts was 133 (SEM 4) s. This was increased by glibenclamide, to 145(6) s, and decreased by lemakalim, to 112(6) s. The time to onset of ischaemic contracture [8(1) min] was accelerated by glibenclamide [4(1) min] and delayed by lemakalim [14(1) min]. Lemakalim significantly improved the recovery of left ventricular developed pressure from 49(7)% in control hearts to 65(3)%, and left ventricular end diastolic pressure from 41(3) to 21(4) mm Hg. Hearts pretreated with glibenclamide showed similar recoveries to control hearts. During reperfusion, lemakalim exerted a transient vasodilator effect whereas glibenclamide caused a transient vasoconstriction. When either glibenclamide or lemakalim was added to a high K+ cardioplegic solution and hearts rendered ischaemic for 35 min, the ability of both compounds to influence ischaemic contracture and postischaemic functional recovery was lost. In additional studies the effect of lemakalim on the relative times to ischaemia induced mechanical failure and electrical arrest was assessed. In control hearts the time to contractile failure was 128(5) s and the time to electrical arrest was 241(30) s, while in the lemakalim treated hearts the values were 103(2) s and 509(161) s, respectively. In the lemakalim group all the hearts showed sustained ventricular arrhythmias; in the control group there were no arrhythmias. CONCLUSIONS: Lemakalim can exert a significant anti-ischaemic effect when given alone. This effect is lost when it is used in combination with high K+ cardioplegia. The anti-ischaemic properties of lemakalim may thus be limited to its ability to accelerate contractile arrest. PMID- 1291084 TI - Effects of glibenclamide on ventricular arrhythmias and cardiac function in ischaemia and reperfusion in isolated rat heart. AB - OBJECTIVE: The aim was to investigate the effects of glibenclamide, a specific blocker of the ATP sensitive potassium channel, on the incidence of ventricular arrhythmias and the functional changes occurring during myocardial ischaemia and reperfusion. METHODS: Hearts (n = 10 per group) were obtained from male Wistar rats, weight 250-300 g. The study was performed in isolated Langendorff perfused rat hearts subjected to ligation of the left coronary artery and reperfusion. Because of the occurrence of arrhythmias, cardiac function was not evaluated during reperfusion. Glibenclamide (1 or 10 microM) was added to the perfusion solution before the coronary artery occlusion, during ischaemia or after reperfusion. In some experiments the incidence of various durations of ischaemia (5, 10, 15, and 30 min) was evaluated. RESULTS: During the preischaemic period, glibenclamide induced a marked reduction in coronary flow, with a slight decrease in heart rate and left ventricular pressure. The ischaemia induced decrease in left ventricular pressure was markedly attenuated when glibenclamide was given before ischaemia. Thus the isovolumetric left ventricular pressure measured after 15 min ischaemia, which represents 59(SEM 6)% of the preischaemic value in the control group, was increased to 82(9) and 94(8)% in presence of glibenclamide (1 and 10 microM, p < 0.05 respectively). The effect was less pronounced when glibenclamide was added to the perfusion fluid during the ischaemic period. None of the hearts showed ventricular fibrillation during the ischaemic period. Glibenclamide (1 and 10 microM) did not reduce the incidence of reperfusion induced ventricular fibrillation. However, a defibrillatory action was observed since glibenclamide reduced the duration of ventricular fibrillation during reperfusion. CONCLUSIONS: Glibenclamide may increase the probability of spontaneous termination of ventricular fibrillation and facilitate the restoration of the myocardial function during regional ischaemia. PMID- 1291085 TI - Regulation of ATP sensitive potassium channel of isolated guinea pig ventricular myocytes by sarcolemmal monocarboxylate transport. AB - OBJECTIVE: The aim was to describe the effects of extracellular application of monocarboxylates (pyruvate, lactate, or acetate) on current through KATP channels (iK,ATP) in isolated guinea pig ventricular myocytes. METHODS: The iK,ATP was elicited during whole cell voltage clamping by application of metabolic poisons, 2,4-dinitrophenol (150 microM) or glucose free cyanide (1 mM) and could be blocked by glibenclamide (3 microM). RESULTS: Extracellular application of monocarboxylates, pyruvate (0.1-10 mM), L-lactate (0.1-10 mM), and acetate (10 mM) led to a rapid inhibition of iK,ATP--an effect which was fully reversible upon washout. Substances without any effect on iK,ATP were (10 mM each) gluconate, citrate, glutamate, creatine, succinate, and glycine. The mechanism underlying the effects of monocarboxylates on iK,ATP was unlikely to be related to an increased ATP production, since D-lactate (10 mM) essentially had the same effect on iK,ATP as the L-isomer of lactate. Furthermore, with intracellular dialysis of alpha-cyano-4-hydroxycinnamate (0.1-0.5 mM), which inhibits pyruvate uptake into mitochondria, extracellular pyruvate exerted the same inhibitory effect on iK,ATP. High concentrations of extracellular alpha-cyano-4 hydroxycinnamate (4 mM), which blocks the sarcolemmal monocarboxylate carrier, prevented the effects on iK,ATP by pyruvate, L-lactate, D-lactate, and acetate. Furthermore, intracellular dialysis with D-lactate (10 mM) led to a more rapid onset of iK,ATP when activated by ATP free dialysis. Activity of isolated KATP channels, measured in isolated membrane patches in the inside out or outside out configuration, typically had a single channel conductance of around 80 pS and was blocked by glibenclamide (3-9 microM). No significant effect of pyruvate was observed in either patch configuration. CONCLUSIONS: In cardiac tissue there may be some modulatory role involving monocarboxylate transport on KATP channel activity, the nature of which is unclear at present but which may involve cytosolic pH changes. Physiological and pathophysiological implications of these findings are discussed. PMID- 1291086 TI - Comparative studies of ATP sensitive potassium channels in heart and pancreatic beta cells using Vaughan-Williams class Ia antiarrhythmics. AB - OBJECTIVE: Actions of cibenzoline and disopyramide, agents with Vaughan-Williams class Ia antiarrhythmic action, on ATP sensitive K+ (KATP) channels were examined in heart and pancreatic beta cells. METHODS: Single ventricular myocytes and beta cells were prepared enzymatically from adult Wistar rat hearts and pancreatic islets. Using patch clamp techniques, KATP channel activities were recorded in whole cell and single channel modes. In whole cell experiments, myocytes were bathed with Tyrode's medium (34 degrees C); inside out patches were bathed with internal solutions (22-24 degrees C) containing 1 microM ATP and varying concentrations of cibenzoline or disopyramide. Myocytes were voltage clamped at 40 mV and glibenclamide blockade conductance was produced by cromakalim. RESULTS: Micromolar concentrations of both cibenzoline and disopyramide suppressed cromakalim induced conductance. When applied to the cytosolic surface of the cell membrane in inside out configuration, both drugs reversibly inhibited single KATP channel activities. Neither unitary conductance nor intraburst fast kinetics was affected by the compounds. At a holding potential of -40 mV under symmetrical approximately 150 mM K+ conditions, half maximum doses (IC50) were 0.9 microM [Hill coefficient (h) = 1.3] for cibenzoline induced block of cardiac KATP channels and 1.8 microM (h = 1.0) for disopyramide block. At +40 mV, IC50 for cibenzoline block was 1.4 microM (h = 0.9). Thus there was little voltage dependence in cibenzoline induced channel block. A similar IC50 value of 2.5 microM (h = 1.2 at -60 mV under symmetrical approximately 150 mM K+) was observed for cibenzoline induced block of KATP channels. CONCLUSIONS: Near therapeutic concentrations of cibenzoline and disopyramide inhibit KATP channel activities in both heart and pancreatic beta cells. This may be causally related to the fasting hypoglycaemia which is sometimes reported in patients receiving the drugs. These antiarrhythmic agents may also modulate myocardial electrical properties during hypoxia or ischaemia. PMID- 1291088 TI - Dofetilide, a new class III antiarrhythmic agent, reduces pacing induced heterogeneity of repolarisation in vivo. AB - OBJECTIVES: The aim was to determine whether dofetilide, a new class III antiarrhythmic agent, could reduce the heterogeneity of repolarisation produced by rapid cardiac pacing and to compare it with quinidine. Increased heterogeneity of repolarisation times may be causally linked to malignant cardiac re-entrant arrhythmias. METHODS: Studies were performed in open chest, artificially ventilated, pentobarbitone anaesthetised beagle dogs of 13 to 15 kg body weight. Myocardial electrocardiograms were simultaneously recorded from 31 electrodes located on the left and right ventricular surfaces of the in situ canine heart. Recordings were obtained over a single cardiac cycle during rapid ventricular pacing at the maximum following frequency. Computer assisted measurements of activation time, activation-repolarisation interval, and repolarisation time were performed and the heterogeneity of these measurements calculated. Measurements were performed before treatment and after each incremental intravenous dose of dofetilide (3, 10, 30, and 100 micrograms.kg-1), quinidine (1, 3, and 10 mg.kg 1), or saline vehicle. RESULTS: Dofetilide increased repolarisation time via a selective prolongation of activation-repolarisation interval, activation time being unchanged. It reduced the heterogeneity of repolarisation time and activation-repolarisation interval, heterogeneity of activation time being unchanged. Quinidine increased repolarisation time by a non-selective increase of both activation-repolarisation interval and activation time. It increased the heterogeneity of activation times which offset a decrease in heterogeneity of activation-repolarisation intervals to produce no change in heterogeneity of repolarisation times. CONCLUSIONS: Dofetilide, but not quinidine, reduces pacing induced asynchrony of repolarisation in the canine heart and this effect may contribute to its antiarrhythmic activity. PMID- 1291087 TI - Blockade of 2,4-dinitrophenol induced ATP sensitive potassium current in guinea pig ventricular myocytes by class I antiarrhythmic drugs. AB - OBJECTIVE: The aim was to assess the effects of various antiarrhythmic drugs on 2,4-dinitrophenol (DNP) induced outward current (IDNP), presumably the ATP sensitive K+ current (IK,ATP) of isolated cardiac cells and to discuss mechanisms involved in the hypoglycaemia which occurs in patients on these drugs. METHODS: The quasi-steady state current-voltage relationship from the isolated guinea pig ventricular cells was measured using whole cell voltage clamp techniques with a ramp pulse programme. The effects of seven different antiarrhythmic drugs on IDNP were examined. Action potentials were elicited at a rate of 0.2 Hz by an intracellular current injection. RESULTS: DNP (50 mumol.litre-1) increased the quasi-steady state outward current at potentials positive to about -60 mV. This current (IDNP) was completely inhibited by the subsequent application of glibenclamide (1 mumol.litre-1), thereby suggesting that the IDNP is probably IK,ATP. Cibenzoline (10 mumol.litre-1, class Ia), disopyramide (30 mumol.litre-1, class Ia), and procainamide (100 mumol.litre-1, class Ia) significantly inhibited the IDNP by 95.5(SD 11.3)%, 77.8(21.2)%, and 76.4(23.9)% respectively. Flecainide (class 1c) inhibited the IDNP by 66.9(23.9)% at 10 mumol.litre-1 but not at 2 mumol.litre-1. Mexiletine (30 mumol.litre-1, class Ib), pilsicainide (50 mumol.litre-1, class Ic), and E4031 (10 mumol.litre-1, class III) at concentrations as high as approximately fivefold the clinically effective blood levels, did not suppress IDNP. Except for 10 mumol.litre-1 flecainide, all the concentrations listed above which blocked IDNP were within twofold of the clinical blood concentrations documented to be effective for suppression of arrhythmias. Cibenzoline, disopyramide, and procainamide, but not flecainide, belong to class Ia antiarrhythmic drugs. All these class Ia antiarrhythmic drugs "shortened" the action potential duration of guinea pig ventricular cells, an opposite change to that noted for multicellular preparations, eg, guinea pig papillary muscles. CONCLUSIONS: Class Ia antiarrhythmic drugs (cibenzoline, disopyramide, and procainamide) inhibit IDNP (presumably IK,ATP) in guinea pig ventricular cells within a range of therapeutic concentrations. This inhibitory effect of IK,ATP can probably explain the hypoglycaemia which occurs in some patients receiving these drugs, and the prolongation of the action potential duration alleged to occur in "superfused" papillary muscles. PMID- 1291089 TI - Class III antiarrhythmic action by potassium channel blockade: dofetilide attenuates hypoxia induced electromechanical changes. AB - OBJECTIVE: The aim was to examine the electromechanical effects of dofetilide, a new class III antiarrhythmic agent, in isolated guinea pig ventricular muscle during hypoxia. METHODS: Hypoxia was induced by superfusing guinea pig right ventricular papillary, muscles with Tyrode's solution gassed with 95% N2 + 5% CO2 [PO2 = 5.3(SEM 1.3) kPa]. Prior to hypoxia, the preparations were either pretreated for 30 min with 0.1 microM dofetilide (n = 6) or with 100 microM glibenclamide (a blocker of ATP sensitive K+ channels, n = 6), or not pretreated (n = 6). Sixteen additional preparations were exposed to 1 mM nicorandil (an activator of ATP sensitive K+ channels) in the absence (n = 6) and presence of dofetilide (n = 6) or glibenclamide (n = 4). Transmembrane action potentials and developed force were recorded using conventional microelectrode techniques and a force transducer. RESULTS: During normoxia, dofetilide markedly increased APD90 from 236(SEM 6) ms to 298(7) ms (p < 0.05) and the effective refractory period (ERP) from 248(5) ms to 315(6) ms (p < 0.05). In the drug free group, 60 min hypoxia decreased APD90 by 47(5)% (p < 0.05), ERP by 48(4)% (p < 0.05) and developed force by 71(6)% (p < 0.05) of baseline, respectively. These hypoxia induced effects were significantly attenuated after pretreatment with dofetilide or glibenclamide. Nicorandil decreased APD90 by 45(5)% (p < 0.05), ERP by 44(6)% (p < 0.05), and developed force by 69(10)% (p < 0.05) of baseline, respectively. Pretreatment with dofetilide or glibenclamide also significantly attenuated the nicorandil induced decreases in APD90, ERP, and developed force. CONCLUSIONS: Dofetilide, like glibenclamide, effectively attenuates hypoxia and nicorandil induced action potential shortening and the associated reduction in contractile force. Thus dofetidile would be expected to retain its antiarrhythmic efficacy during myocardial hypoxia or ischaemia. PMID- 1291090 TI - Antiarrhythmic and electrophysiological effects of amiodarone, lignocaine, and penticainide in anaesthetised rats. AB - OBJECTIVE: The aim was to correlate the relative abilities of amiodarone, lignocaine, and penticainide in suppressing ventricular tachyarrhythmias in response to coronary artery occlusion with their relative abilities to prolong ventricular functional refractory periods and to reduce intraventricular conduction velocities in anaesthetised open chest rats. METHODS: Functional refractory period was measured with a paired electrical stimulation technique. Intraventricular conduction velocity was monitored using the QRS duration of the ECG. RESULTS: Low doses of these three drugs were selected which protected against ventricular tachyarrhythmias induced by coronary occlusion. These doses prolonged the functional refractory period without increasing QRS duration. High doses of both amiodarone and lignocaine were more effective than low doses in suppressing coronary occlusion induced ventricular tachyarrhythmias. Such high doses greatly prolonged the functional refractory period but prolonged the QRS duration only moderately. In contrast, higher doses of penticainide failed to inhibit coronary occlusion induced ventricular tachyarrhythmias. These higher doses of penticainide prolonged the functional refractory period but prolonged the QRS duration even more markedly. CONCLUSIONS: Among these three drugs an increase in functional refractory period appears to be antiarrhythmic. In contrast, widening of the QRS complex without a corresponding increase in functional refractory period, as produced by penticainide, appears to counteract the antiarrhythmic effect. PMID- 1291091 TI - Differential block of cardiac delayed rectifier current by class Ic antiarrhythmic drugs: evidence for open channel block and unblock. AB - OBJECTIVE: The aim was to compare the effects of the class Ic antiarrhythmic drugs flecainide, encainide, and recainam on the delayed rectifier current, IK. METHODS: Membrane currents were studied using the single suction pipette voltage clamp technique in freshly dissociated cat ventricular myocytes bathed in HEPES buffered physiological saline at 32 degrees C. RESULTS: Flecainide and encainide decreased IK with IC50 values of 2.1 microM and 6 microM, respectively. Recainam (100 microM) reduced IK by only 7 (SEM 3)% after 20-30 min exposure and by 19% after an 80 min exposure (IC50 > 400 microM). None of the compounds blocked the inward rectifier, IK1. Block of IK by flecainide and encainide increased with depolarisation following a voltage dependence similar to that describing channel activation. Flecainide and encainide also slowed the time course of the IK tail currents, consistent with drug dissociating from open channels. CONCLUSIONS: The observed voltage dependence for IK block by flecainide and encainide resembles the interaction reported between these agents and the excitatory sodium channel, ie, depolarisation enhances block while repolarisation leads to removal of block. The results further suggest that the electrophysiological profile of class Ic agents can have a markedly different ionic basis, ie, K+ channel block by flecainide and encainide is balanced by a potent block of sodium channels, while recainam appears to be a weak but relatively specific blocker of sodium channels only. These differences are not readily accommodated by the current Harrison Vaughan-Williams classification scheme, and suggest the possibility that potentially important drug specific differences can exist within the same antiarrhythmic drug class. PMID- 1291092 TI - Differential inhibition of potassium currents in rat ventricular myocytes by capsaicin. AB - OBJECTIVE: Capsaicin is a pungent irritant present in peppers of the Capsicum family. Its major target of action is believed to be sensory neurones. Capsaicin has also been shown to prolong cardiac action potential in atrial muscle, perhaps by local release of calcitonin gene related peptide which in turn enhances inward calcium currents. However, capsaicin has been shown to inhibit K+ current in neurones. Since such an action could contribute to action potential prolonging activity of capsaicin in heart, the aim of the study was to examine the effects of capsaicin on cardiac K+ currents. METHODS: Ionic currents and action potentials were examined in isolated adult rat ventricular myocytes using the whole cell variant of the patch clamp technique at 25 degrees C. RESULTS: Capsaicin (10 microM) increased the action potential duration (APD50) from 45 ms to 166 ms. This effect was associated with an inhibition of three distinct K+ currents. The decreasing rank order of potency was: transient outward K+ current (ITO, IC50 = 6.4 microM), a voltage dependent non-inactivating outward current (IK, IC = 11.5 microM), and the inward rectifier K+ current (IK1, IC50 = 46.9 microM). Capsaicin induced block of ITO was characterised by a decrease in the peak current amplitude and an increase in the rate of inactivation. The inactivation of ITO in the absence of capsaicin was well described by a single exponential [tau = 77 (SEM 2) ms at +40 mV, n = 10]. However, in the presence of 10 microM capsaicin inactivation was best described by the sum of two exponentials [tau FAST = 4.4(0.5) ms; tau SLOW = 92.4(3.0) ms, n = 10] with the fast component contributing 46(2)% of the total decay. A small but consistent hyperpolarising shift (approximately 3 mV) in the steady state voltage dependence of inactivation of ITO was induced by 10 microM capsaicin. Capsaicin had no effect on the rate of ITO recovery from inactivation (tau = 49 ms and 48 ms for control and drug respectively). The capsaicin analogue, resiniferatoxin, which as an irritant is up to 10(4)-fold more potent than capsaicin, had no effect on any of the K+ currents when present at concentrations of up to 10 microM. In contrast another capsaicin analogue, zingerone (30 microM) blocked ITO by 52(12)% and IK by 35%. CONCLUSIONS: Capsaicin produces a prolongation of the rat ventricular action potential, an effect which is associated with inhibition of potassium currents. PMID- 1291093 TI - Differential effects of the new class III antiarrhythmic agents almokalant, E 4031 and D-sotalol, and of quinidine, on delayed rectifier currents in guinea pig ventricular myocytes. AB - OBJECTIVES: The effects of almokalant (4-[3-ethyl[3-(propylsulphinyl)propyl] amino]-2-hydroxy-propoxy]- benzonitrile), E-4031 (1-[2-(6-methyl-2-pyridyl) ethyl]-4-(4-methylsulphonyl-amino- benzoyl)piperidine), d-sotalol, and quinidine were investigated on the delayed K+ rectifier current IK. The aim of the study was to compare the drug action on the two components of this current. METHODS: Membrane currents were measured in ventricular myocytes from guinea pig hearts with the whole cell voltage clamp technique. IK was activated during clamp steps from a holding potential of -40 mV to test potentials -30 and +50 mV. The tail current Itail was measured upon stepping back to holding potential. RESULTS: In control experiments. IK and Itail declined spontaneously ("run down"). With 300 ms long test pulses to +50 mV, only d-sotalol (10(-4) M) caused a significant further decrease in IK, whereas all four agents significantly reduced Itail (almokalant 10(-6) M, E-4031 10(-7) M, quinidine 10(-5) M). When tested with 1 s long clamp steps at various potentials almokalant (3 x 10(-6) M), E-4031 (10(-6) M), quinidine (10(-5) M), and d-sotalol (10(-4) M) reduced IK in the potential range between -20 and +40 mV, yielding a bell shaped inward rectifying drug sensitive current. Itail was reduced by almokalant and E-4031 over the whole voltage range with saturation of block positive to +20 mV. Similar reductions with quinidine but not with d-sotalol were also significant. With rest pulses to +50 mV of increasing duration (25 ms-4000 ms), Itail developed with a faster time course than IK and therefore the ratio of Itail/IK declined with pulse duration. With almokalant and E-4031, this ratio became independent of test pulse duration. For 250 ms pulses, Itail/IK was also significantly reduced by d-sotalol and quinidine. CONCLUSION: Inhibition of the rapidly activating inwardly rectifying component of IK is prominent with almokalant and E-4031 and less pronounced with d-sotalol and quinidine. Since inhibition of this component prolongs the cardiac action potential, it should contribute to the antiarrhythmic properties of the agents. PMID- 1291094 TI - Channel "selectivity" and evolution. Has evolutionary pressure and natural selection provided the ATP sensitive potassium channel in the myocardium as an endogenous protection against ischaemic heart disease? PMID- 1291095 TI - Glibenclamide and cardiac function during ischaemia. PMID- 1291096 TI - KATP channel opening and cardioprotection. PMID- 1291097 TI - 2,4-Dinitrophenol induced outward current. PMID- 1291098 TI - A computer "brain" for dentistry? PMID- 1291099 TI - And the beat goes on. PMID- 1291100 TI - Impact of overbite on indicators of temporomandibular joint dysfunction. AB - Epidemiological studies have suggested that deep overbite is associated with symptoms of temporomandibular dysfunction (TMD). This finding was directly tested by deliberately constituted groups of deep and normal overbite subjects matched for age and sex. Eighty-one subjects participated. Dependent measures included the TMJ Scale test; measures of muscle activity in the right and left frontalis, temporalis, and masseter muscles; and pressure threshold meter readings for the same sites. The results showed no differences between deep and normal overbite subjects for all the dependent measures studied. The role of overbite alone in producing TMD symptoms is questioned. PMID- 1291101 TI - Attributes of tinnitus that may predict temporomandibular joint dysfunction. AB - A collection of 1002 patients with severe tinnitus, drawn from the Tinnitus Data Registry, were retrospectively surveyed to determine which traits or attributes of tinnitus could indicate the possibility of temporomandibular joint dysfunction (TMD) as the cause of tinnitus. The patients were divided into two groups: (1) a TMD group, consisting of 69 patients for whom there was no known cause of tinnitus except for one or more temporomandibular joint (TMJ) indicators, and (2) a comparison group with mixed etiologies (n = 860). Seventy-three patients were eliminated due to excessive complications relating to cause. The two groups were compared seeking those attributes of tinnitus that significantly separated them. No single benchmark standard was discovered that exclusively indicated tinnitus from TMJ origins. However, a total of 10 "TMJ Indicators" were discovered. The data for each of these indicators is presented and discussed. In addition, the attributes that did not significantly separate the two groups are listed. The study concludes with a recommendation for TMJ referral for those tinnitus patients with unknown etiology who demonstrate any three or more of the TMJ indicators. PMID- 1291102 TI - The distribution of internal derangement in patients with temporomandibular joint dysfunction--prevalence, diagnosis, and treatments. AB - This study consisted of 355 patients referred to a surgical practice complaining of facial pain, temporomandibular joint (TMJ) sounds, and limited jaw opening. In 247 patients, 360 TMJs were evaluated by arthrography. While 72.2% of them had internal derangement, the remaining 27.8% had normal arthrograms (NID). Among the patients with internal derangement, meniscal displacement with reduction (MDR) was the largest group (47.3%), followed by meniscal displacement without reduction (MD) (32.3%), meniscal displacement without reduction associated with perforation (MDP) (15.4%), and perforation with normal disk position (P) (5.0%). The NID, MDR, and MD groups showed similar age distributions. The MDP and P groups showed a significantly older mean age. Gender distribution was biased toward females (82.0%). Of the total number of joints, 183 (50.8%) had a history of trauma, 69.9% of which had an internal derangement. In terms of treatment, 100% of the NID group was treated by splint therapy. The MDR group was mostly treated by partial meniscectomy (49.6%) and splint therapy (41.5%). The MD group was mostly treated by total meniscectomy (53.6%) followed by splint therapy (32.1%). The MDP or P groups mostly underwent total meniscectomy (72.5% and 61.5%, respectively). PMID- 1291103 TI - Influence of stabilization occlusal splints on sternocleidomastoid and masseter electromyographic activity. AB - The present work was conducted in order to determine the effect of stabilization occlusal splints on electromyographic (EMG) activity of sternocleidomastoid and masseter muscles, in subjects with tenderness to palpation in these muscles. A full-arch maxillary stabilization occlusal splint was made for each of 14 subjects. Tonic EMG activity, as well as during saliva swallowing and maximal voluntary clenching, was recorded with and without a stabilization occlusal splint inserted. Similar tonic, as well as maximal voluntary clenching EMG activity, with and without the stabilization occlusal splint, was observed. During saliva swallowing, the activity in both muscles was significantly lower with the stabilization occlusal splint. This suggests that daytime use of the stabilization occlusal splint might improve tenderness to palpation in the studied muscles, since the frequency of swallowing function is higher during waking hours. PMID- 1291104 TI - Vectorial analysis of the instantaneous equilibrium of forces between incisal and condylar guidances. AB - Protrusive functional relationships between the upper and lower jaws are constrained by the structures of the temporomandibular joints (TMJs) and the opposing contacting surfaces of the anterior teeth. To check these biomechanical relationships, the link quadrilateral bell crank model was assumed in order to compute the instantaneous equilibrium of forces using vectorial analysis. Four anterior teeth configurations were analyzed to study the distribution of force components. The first represented normal bite (used as control), the second represented long anterior overjet, the third represented deep anterior overbite, and the fourth one represented freedom in centric. When three different interincisal contact positions were assumed, functional compromises concerning load/reaction between the TMJ and anterior dentition were found. In centric occlusion there was a tendency toward less loading in the joints and increased loading on the dentition. In intermediate positions and close to the edge-to-edge position, the mechanical tendencies were toward increased loading in the joints and decreased loading on the dentition. PMID- 1291105 TI - Cine magnetic resonance imaging of the temporomandibular joint. AB - Magnetic resonance imaging (MRI) provides a significant amount of information about both the position of the meniscoligamentous complex and the osseous structures in evaluation of internal derangements of the temporomandibular joint (TMJ). With the advent of computer-driven cine displays, dynamic information is now available, providing cost-effective diagnostic evaluation similar to cine fluoroscopy with arthrography, but without the ionizing radiation exposure or discomfort. Using a bite block, a series of sagittal images are obtained with the patient "posing" at different degrees of jaw opening. The subsequent cine MRIs with "posed" motion are striking and very helpful in evaluating various types of TMJ dysfunction. At the authors' institution, 205 patients were examined with a history of TMJ arthralgia. Correlation of imaging studies and surgical findings reveals a sensitivity (98%) and specificity (96%) for identifying the meniscoligamentous complex. PMID- 1291106 TI - Adverse events of acupuncture and occlusal splint therapy in the treatment of craniomandibular disorders. AB - Occlusal splint therapy and acupuncture have been found to provide positive treatment in a number of studies. As with other therapies, adverse events may occur. In this paper, adverse event refers to any reaction to a treatment besides the intended treatment effect--irrespective of any correlation between the treatment and the reaction. This reaction can be positive, as well as negative, to the patient. In the present study, 61 patients with craniomandibular dysfunction (CMD) were treated with acupuncture or occlusal splint therapy and the adverse events were carefully recorded. The results show that the profile of the adverse events differed between the two treatment modes. Acupuncture seemed to have adverse events of a more general nature, e.g., relaxed feeling, improved sleep, temporarily increased pain; whereas, adverse events of occlusal splint therapy seemed to be more locally related to the orofacial region, e.g., increased/decreased salivation and tension in the teeth. The majority of the patients responded positively to both treatment modalities. Only in a few cases did the patients consider the treatment uncomfortable. No serious adverse event or complication was observed in this study. PMID- 1291108 TI - Diagnosing referred otalgia: the ten Ts. PMID- 1291107 TI - Modified use of a dynamic bite opener--treatment and prevention of trismus in a child with head and neck cancer: a case report. AB - Trismus may be a complication arising during or after treatment of patients with head and neck cancer. Treatment of trismus is difficult, making prevention very important. To prevent and treat trismus in a patient with a nasopharyngeal tumor, the Contract-Relax-Antagonist-Contract (CRAC) technique was applied, with the aid of a custom-made dynamic bite opener (DBO). The CRAC technique in combination with the DBO, as a therapy/prevention program for trismus, is not referred to in the literature. The combination of CRAC and DBO appeared to be a gentle and effective method well tolerated by the patient. PMID- 1291109 TI - Stress: a chain reaction. PMID- 1291110 TI - [A new modification of the horse erythrocyte agglutination test for the detection of heterophilic antibodies in infectious mononucleosis]. AB - The new modification (HEA test) is based on the presence of a singularly distinct agglutination of native horse erythrocytes in a serum dilution 1:10 and more from cases with Epstein-Barr virus infectious mononucleosis. In 1665 sera the HEA test was equally often positive as the OCH test (in 5.2%) whereas the IM test with formal-treated horse erythrocytes was positive only in 3.7%. The sensitivity of the IM test in comparison with the OCH test was 61%, the specificity 99.5%. The sensitivity of the HEA test in comparison with the OCH test was 76%, the specificity 98.7%. The specificity of the HEA test in a group of 52 sera without IgG antibodies to EB-viral capsid antigen (EB VCA) was 94%, in another group of 130 sera from hepatitis cases it was 98%. In 103 pairs of sera from infants aged 1-5 years the positivity of the OCH test, HEA test, IgM antibodies to EB VCA and the four-fold rise in the titre of EB-viral IgG were, 20%, 16%, 23% and 24% respectively. Analogous values in 159 pairs of sera from older subjects were 42%, 40%, 38% and 29%. The HEA test is recommended as useful adjunct to the OCH test for the detection of heterophile antibodies even in young children. PMID- 1291111 TI - [Use of markers of hospital strains in studying the occurrence of nosocomial infections]. AB - The submitted paper deals with one of the possible aspects of the investigation of nosocomial infections, i.e. investigations of the properties of hospital strains, their importance and possible use. The incidence of bacterial hospital strains was investigated in a surgical department of a district hospital of the North Bohemian region in October 1990; at the time of the survey 29 nosocomial infections (36.1%) were revealed by the prevalence method. Bacterial hospital strains were isolated from patients with a nosocomial infection, from the attending staff and the hospital environment. The following markers were investigated: biotyping, phagotyping, serotyping, toxin production, sensitivity to antimicrobial substances and sensitivity to disinfectants. Based on results of marking of hospital strains 7 incidences with a possible epidemiological association were detected where the hospital strain of equal or very similar properties dominated. The results of the investigation confirmed the important participation of the attending staff in the spread of nosocomial infections, in particular via contaminated hands, and drew attention to shortcomings as regards adherence to the hygienic and epidemiological regime in the investigated department. PMID- 1291112 TI - [Filamentous micromycetes in otitis]. AB - In 1984-1991 in the microbiological laboratory in Komarno (Slovak Republic) 4224 (100%) smears with the diagnosis of otitis were examined. From 138 (3.26%) of smears microscopic filamentous fungi were isolated, most frequently aspergillae from the group Aspergillus niger (34.1%), Aspergillus flavus (29.8%) and Aspergillus fumigatus (21.8% of 138 isolates). The strains of other species of filamentous micromycetes were found only rarely. A review on the incidence of filamentous micromycetes in otitis in different regions, based on data in the literature is presented. PMID- 1291113 TI - [Phagotypes of the Salmonella paratyphi B strains isolated in Czechoslovakia 1986 1991]. AB - The author presents an account of phagotypes of 70 strains of Salmonella paratyphi B isolated in 1986-1991 incl., from patients suffering from typhus B and registered carriers, isolates from river water and also from three new cases of carriers in Czechoslovakia. These isolated strains were sent for typing of Salmonellae to a Bratislava department for phagotyping. According to lytic findings with standard bacteriophages the strains were classified into 8 types. Another group is formed by strains which cannot be typed in the critical dilution (RTD) nor in its tenfold concentration (19.1%). During the investigation period the subtype 3aI (38.3%) and the phage type Taunton (21.9%) were most frequent. PMID- 1291114 TI - [Immunochemical determination of gentamicin in serum. III. The competitive ELISA]. AB - The author describes the use of polyclonal antibodies against gentamicin by competitive ELISA. The author used polystyrene microplates as the solid phase for antibodies. Gentamicin was marked by horse radish peroxidase and a known amount of thus labelled gentamicin competed for a bond with an antibody with an unknown amount of gentamicin in serum. The method requires 10 microliters non-diluted serum and the results can be evaluated within one hour. The accuracy of the method according to values of the coefficient of variation (CV) is 9.0-13.2% in different tests and 5.2 to 9.2% within one examination. PMID- 1291115 TI - [Microbicidal effect of Lautercide, a new disinfectant]. AB - The authors tested the effect of a new disinfectant Lautericide produced by Qualichem Co. Neratovice which contains as the active agent acetate amine of coconut acid. For experiments standard methods were used and standard strains for testing of the following microbial strains: St. aureus, E. coli, Ps. aeruginosa, Proteus vulgaris, Serratia marcescens, Candida albicans, spores of Bacillus subtilis, M. tuberculosis, M. fortuitum, M. avium. As a model virus E. coli bacteriophage OX 174 was used. In concentrations from 0.04% to 0.5% and exposures from 2 to 10 minutes Lautercide exerted a bactericidal and fungicidal action. On spores of B. subtilis the preparation was ineffective even in a 10% concentration and 32-minute exposure. Devitalization of mycobacteria occurred after 15 min. action of Lautercide on M. tuberculosis and M. fortuitum, in M. avium in a 10% concentration in 60 min. Lautercide is ineffective against small resistant viruses without an integument. It is recommended to use Lautercide in a 1% aqueous solution for a one-stage disinfection combined with cleaning in the health services, veterinary medicine and in the field of communal hygiene. Before cleaning objects contaminated with infectious material, 5% Lautercide with 30 min. exposure is recommended. In disinfection of objects contaminated with mycobacteria it is recommended to use a 5% solution with 10-minute exposure for M. tuberculosis and M. fortuitum and a 10% solution for M. avium with 60-minute exposure. PMID- 1291116 TI - [Findings of body lice (Pediculus humanus L.) in Czechoslovakia]. AB - The first finding of body lice in Czechoslovakia since year 1945 is demonstrated. The determination of the species is based on the location of the louse on the body of the infested person and on the significant differences in the length of tibia of middle legs in these lice and those collected from the head of children. Local eradication was achieved by using formulation containing permethrin, against head lice. PMID- 1291117 TI - [Natural foci of tick-borne encephalitis in the Slovak Republic and its relation to the natural ecosystem]. AB - To evaluate the incidence of natural foci of tick-borne encephalitis in the Slovak Republic data of the hygiene service on the morbidity from tick-borne encephalitis during the period from 1961-1988 were used as well as data from the literature and results of the author's field studies on the incidence of the common tick. The main foci of tick-borne encephalitis are in the West Slovakian region, in the Zahorske lowland, in the Vah valley up to the distrikt of Povazska Bystrica, in the area of the Low Carpathian mountains, Tribec, Vtacnik, the Nitra and Hron hills, and Kovacov hills, in the Central Slovakian region in the Krupin hills and in the East Slovakian region in the Slovak karst and Slanske hills. The incidence of common ticks and foci of tick-borne encephalitis is linked to the original oak grove communities. In Slovakia the latter comprise hornbean and oak forests, oak groves and thermophile oak forests. Areas of original communities of beech woods and spruces which grow in higher altitudes do not provide favourable conditions for the development of the common tick. Rare foci of tick-borne encephalitis of a mountainous type found in Slovakia survive probably due to the extremely favourable microclimatic conditions in these areas. Also the hygrophilous communities of alders, moorlands and dry steppes, original as well as cultivated ones, are not suitable for the common tick. This is why ticks are not found in central, northern and northeastern Slovakia, in the Rye island and lowland along the Tisa river.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291118 TI - [A revolution in the therapy of leprosy]. PMID- 1291120 TI - [Biological activity of salicylanilides]. PMID- 1291119 TI - [The effect of potential beta-adrenolytic agents on oxidation and phosphorylation processes in myocardial muscle mitochondria in vitro]. AB - Concentrations ranging from 1-9 x 10(-7) mol.dm-3 were employed for in vitro studies. Under the selected experimental conditions, both agents markedly decreased the stimulated consumption of oxygen by the cardiac muscle mitochondria in the condition S3, the rate of the formation of energy by mitochondria as well as the respiratory control index. The coefficient of oxidative phosphorylation was not markedly changed due to the effect of the added agents. The results of the present paper suggest possible integration of the cardiac muscle mitochondria in the oxidative metabolism of the potential beta-adrenolytic agents FA33 and FP33, which requires further in vivo studies. PMID- 1291121 TI - [Biological effects of anthraquinones. III. Effect on microorganisms and as a repellent]. PMID- 1291122 TI - [Dynamics of the distribution of lymphocyte subpopulations in the human menstrual corpus luteum]. AB - Recent evidence suggests that immunoendocrine interactions play a definitive role during development and regression of the human menstrual corpus luteum (hmCL). We studied the distribution of immune cells within individual structures of hmCL during various stages of its development. Immunoperoxidase-stained ultra-thin frozen sections were evaluated, using light microscopy fitted with an image analysis system. The results suggest that monocytes/macrophages and MHC class II positive cells are the most prominent immune cells within the hmCL throughout its lifespan. Both cell types are concentrated within the trabeculae. In addition, MHC class II positive cells are abundant also within the granulosa-luteal layer. T helper/inductor (Th/i) and T cytotoxic/suppressor (Tc/s) cells were detected only in minor amounts within the thecal trabeculae of mature tissue. Possible links between the occurrence and functional roles of the immune cells studied are discussed. PMID- 1291123 TI - [Cell-mediated immune reactivity to sperm in disorders of human reproduction]. AB - Besides the pathological anti-sperm humoral immunity, pathological anti-sperm cell-mediated immunity is considered as a crucial facet of the disturbances of human reproduction (male and female infertility, recurrent abortions, endometriosis, late EPH gestosis, fetal hypotrophy). A precise and objective method is designed, based on a one-step agarose Leukocyte Migration Inhibition Factor assay. The migration areas are evaluated by a computer-assisted image analysis system. Optimal concentrations of leukocytes and sperm, as well as technical conditions are described. The Radius Migration Indexes and Area Migration Indexes are computed and expressed as a Migration Index percentage for each patient or control. Preliminary clinical results indicate a highly significant association between leukocyte migration inhibition and cases of "immunopathological" infertility and repeated fetal loss. PMID- 1291124 TI - [One-year follow-up of women treated with transdermal administration of estrogen for post-castration and climacteric syndromes]. AB - Having gained preliminary knowledge in a selected group of 64 patients treated for three months by a transcutaneous form of estrogen therapy (Estraderm TTS) for postcastration and climacteric syndromes, the authors report in this paper on the results of a one-year follow-up of a series of 42 patients treated by ETTS 25 and 50 for the same diagnoses. Administration of ETTS makes it possible to take advantage of the therapeutic transdermal system for the transfer of 17 beta estradiol directly into the blood stream. Estradiol in a daily dose of 25, 50 or 100 microgrammes is deposited in ethanol gel as a reservoir in a special sticking tape. From there it is absorbed across a microsporous membrane by molecular diffusion into the subcapillary plexus at a constant speed till an equilibration of the diffusion gradient between skin and the system is attained. For the aim of this study is to evaluate both the recession of the subjective as well as objective complaints in patients suffering from postcastration and climacteric syndromes and the reflection of the treatment in the blood levels of gonadotropins, estrogens, gestagens and cortisol and likewise the vaginal hormonal cytology. Both the systemic and local side-effects of treatment are subject to a careful study. On the basis of a comprehensive statistical study of these changes in every patient as well as in the whole series in the course of one year the authors reach the conclusion that the ETTS administration strikingly improves the subjective as well as objective complaints of the patients, and, in agreement with the literary data, objectively influences the laboratory results concerning especially the circulating levels of gonadotropins and of estradiol. In conclusion, the authors comment on the favourable contribution of this form of treatment to gynaecological practice in the therapy of postcastration, climacteric and estrogen-losing syndromes. A special modification of the record was prepared for this study when the running subjective evaluations of the effect of the treatment by the patient, as obtained in the course of directed interviews, as well as objective results of somatic and laboratory changes including the aggregate yearly evaluation of the effect of the treatment in every individual woman of the series are clearly arranged. PMID- 1291125 TI - [Results of the Cattell 16 P.F. questionnaire in pregnancy]. AB - Cattell's 16 P. F. Personality Questionnaire was used to examine 31 randomly selected pregnant women with a mean age of 24.9 years. The first and second examinations were performed at weeks 14-16 and 36-38 of pregnancy, respectively. While 13 women were examined using A form first, followed by B form, the sequence was reversed in 18 women. Results were evaluated by means of vector regression analysis. The difference in results of examination at the beginning and end of pregnancy was zero, however, there was a significant difference (p < 0.01) in the group with the AB sequence of questionnaire completion from that with the BA sequence. The difference applies especially to factors A, F, I and Q2. PMID- 1291127 TI - [Importance of ultrasonography in the early diagnosis of ectopic pregnancy]. PMID- 1291126 TI - [Present surgical approach to treatment of endometrial carcinoma]. AB - The authors present the histological evaluation of preparations collected during surgery during treatment of endometrial carcinoma in a clinical group of 199 women. Decision on subsequent therapeutic procedures depends on the bioptic risk of the score which comprises the type and grading of the tumour, angioinvasion and possible spread. Subsequent adjuvant therapy according to the above criteria was administered to 50% of the women. The classification grade, as compared with the preoperative stating, was raised in almost 40% of the women. The asset of evaluation of the risk score is establishment of a more accurate diagnosis and formulation of corresponding adjuvant therapy. PMID- 1291128 TI - [Personal experience in management of labor using continuous epidural analgesia]. PMID- 1291129 TI - [Recombinant human FSH in clinical practice and future perspectives]. PMID- 1291130 TI - [Lactobacilli, bacterial vaginosis and mycotic colpitis]. PMID- 1291131 TI - [An unusual complication of the Mayer pessary]. PMID- 1291132 TI - [History of women's health care in Czechoslovakia--IV]. PMID- 1291133 TI - [Cancer of the uterine cervix in the Czech Republic 1977-1988]. PMID- 1291134 TI - Malaria transmission in Sri Lanka compared to Africa. PMID- 1291135 TI - Biorhythms. PMID- 1291136 TI - Reducing tobacco use in Sri Lanka. AB - Tobacco use is steadily declining in wealthy countries, whereas it is increasing in poor countries. Approaches found successful in wealthy countries should be applied vigorously in Sri Lanka too. This requires sustained and active lobbying, especially by doctors. Some promising strategies are already being used in Sri Lanka which indicate that countries such as ours could develop appropriate local approaches in addition to those found useful in rich countries. These have evolved with little active support from the medical profession. If doctors actively complement these efforts, Sri Lanka could provide a model in successful smoking control for poor nations. PMID- 1291137 TI - Serum precipitins in pulmonary aspergillosis: preliminary results. AB - Definitive diagnosis of pulmonary aspergillosis is difficult to establish. Thus, confirmative evidence of active fungal aggression is imperative. In this study, an immunodiffusion test was carried out on 36 cases of pulmonary aspergillosis and two groups of subjects comprising 133 patients with non-fungal diseases and 134 healthy volunteers as controls. The test was positive in 92.3% of the patients with mycetoma, in 50% of the patients with allergic bronchopulmonary aspergillosis, and in 25% of the patients with invasive aspergillosis. Results were negative in all subjects in the two control groups. The findings indicate the efficacy of the test under study for supporting the diagnosis of pulmonary aspergillosis. PMID- 1291138 TI - Screening for Turner syndrome: how useful is the buccal smear test? AB - The buccal smear test was used to screen for Turner syndrome in a sample of girls with severe short stature who did not have any other clinical features of that condition. The majority of the girls did not show X chromatin bodies in the buccal mucosal cells. None of those who qualified for chromosomal analysis showed an XO chromosomal pattern either. We conclude that reliability of the buccal smear test as a screening method for Turner syndrome remains doubtful. PMID- 1291139 TI - Intensive care experience in Guillain-Barre syndrome. AB - In a retrospective study of 34 patients with acute Guillain-Barre syndrome admitted to an intensive care unit (ICU) during a six year period from January 1984 to December 1989, for bulbar paresis or impending respiratory failure, 4 required endotracheal intubation to protect the airway, and 27 required mechanical ventilation. A high incidence of respiratory complications was noted. Two patients died of cardiovascular instability. Close monitoring of respiratory and cardiovascular status is essential to ensure survival. PMID- 1291140 TI - Synthetic mesh in the repair of incisional hernia. AB - A series of 30 incisional hernia repairs with knitted monofilament polypropylene is presented. The recurrence rate was 3.3% (one patient). No patch has sloughed or required removal. There was one postoperative death. Synthetic mesh allows defects of any size to be repaired without tension with a low recurrence rate. PMID- 1291141 TI - Medicinal plants. PMID- 1291142 TI - Is congenital dislocation of the hip rare in Sri Lanka? PMID- 1291143 TI - Charles Darwin's anthropological observations on Ceylonese. AB - In his 1871 work, The Descent of Man and Selection in Relation to Sex. Darwin has made three anthropological observations pertaining to the nose, beard and polygamy in Ceylonese. He never visited Ceylon, and his observations were based on the works of Sir J. Emerson Tennent (1859) and Sir J. Lubbock (1865). PMID- 1291145 TI - [Application of electromicroscopy in the pathologic diagnosis]. PMID- 1291144 TI - Adult filarial worm (Wuchereria bancrofti) in a benign ovarian tumour. AB - A case of an adult filarial worm (Wuchereria bancrofti) associated with a benign ovarian tumour and a cyst is presented. Possible reasons for the findings of a well preserved part of the worm and a foreign body granuloma in the lymphatic subendothelium are discussed. PMID- 1291146 TI - [An ultrastructural classification of carcinomas of the lung]. AB - For the purpose of providing more accurate histological typing of lung carcinoma, it is necessary to classify carcinomas of the lung by electron microscopy. One hundred and fifty cases of resected lung carcinoma were examined under electron microscope. The results of ultrastructural typing of lung carcinoma were as follows: 1. carcinomas showed differentiated features of glandular and squamous epithelium, including squamous cell carcinoma (28 cases), adenocarcinoma (35 cases), and adenosquamous carcinoma (29 cases). Among them, some cases were associated with neuroendocrine differentiation. In addition, solid mucinous cell carcinoma (4 cases) and adenoid cystic carcinoma (2 cases) were seen. 2. Carcinomas showed differentiated features of bronchioloalveolar epithelium, subdividing into clara cell (9 cases), type II pneumocyte (3 cases), mucinous cell (5 cases) and mixed type (4 cases). 3. Carcinomas showed differentiated features of neuroendocrine cell (Kulchitsky cell), including well differentiated (carcinoid, 13 cases), intermediately differentiated (atypical carcinoid, 12 cases), and poorly differentiated (small cell carcinoma, 6 cases). Among them, some cases were associated with squamous differentiation. The ultrastructural classification was compared with histological classification of lung carcinomas and the differences between them are discussed. PMID- 1291147 TI - [The ultrastructural characteristics of minor glomerular abnormalities]. AB - Among 1168 patients in whom clinical data and light microscopic, immunofluorescence and electron microscopic findings of renal biopsies were available, 329 had minor glomerular abnormalities. These 329 cases included 38 with glomerular minimal change (MC), 32 with glomerular minor lesion, 143 with mild mesangioproliferative GN, 14 with mild mesangioproliferative IgM nephropathy, 4 with C1q nephropathy, 37 with IgA nephropathy, 12 with Henoch Schonlein purpura GN, 17 with lupus nephritis, 16 with early stage membranous nephropathy (eMN), 4 with Alport's syndrome (ALS), 7 with thin basement membrane nephropathy (TMN) and 5 with nonglomerular haematuria. Their histologic appearances were nearly normal, and immunofluorescence was negative or mild positive. But electron microscopic appearances were diagnostic. Electron microscopy is the only diagnostic method for MC, ALS, TMN and eMN. PMID- 1291148 TI - [Application of electron microscopy in the diagnosis of neoplasms]. AB - The majority of neoplasms can be diagnosed by light microscopy, but in some cases the diagnosis remains ambiguous due to poor differentiation, even though special stainings have been employed. This paper presents 34 cases of neoplasms in which the tumors were diagnosed by electron microscopy. This includes distinguishing (1) anaplastic carcinoma from lymphoma; (2) anaplastic carcinoma from amelanotic melanoma; (3) APUDoma from other tumors; (4) different mesenchymal tumors. The diagnoses of 4 cases of malignant melanoma, 11 cases of APUDoma, 7 cases of poorly differentiated carcinoma or anaplastic carcinoma, 2 cases of non-Hodgkin's lymphoma, 9 cases of mesenchymal tumors and 1 cases of other tumors have been resolved by electron microscopy. It is obvious that in some cases, electron microscopy can be of help in establishing a correct diagnosis. PMID- 1291149 TI - [Histopathological and immunopathological studies on experimental pulmonary candidiasis]. AB - Experimental pulmonary candidiasis was produced by intratracheal inoculation of candida albicans in mice. The pathological changes could be divided into two stages, dominated by polymorphonuclear leukocyte infiltration and granuloma formation respectively. Preincubation of C. albicans with mouse anti-C. albicans antibody showed no obvious effect on pathological changes of the lungs as compared with the changes in the control mice, indicating that specific antibody did not play a crucial role in the defence mechanism of the lungs against C. albicans infection in normal mice. In the mice injected with antineoplastic drugs and hormones, abundant pseudohyphae were found in the lungs. Tissue necrosis and hemorrhage were obvious. PMID- 1291150 TI - [Observation on the phenotypic changes of tumor-infiltrating lymphocytes(TIL) during cultivation in vitro]. AB - Tumor-infiltrating lymphocytes (TIL) were isolated from 5 malignant tumors and their phenotypes were analyzed by flow cytometry when co-cultured with recombinant human interleukin-2 (rIL-2). It was shown that 84% (+/- 8%) of TILs were OKT3+in phenotype after three weeks of cultivation. Among these, OKT8+subpopulations amounted to 77%(+/- 13%), while OKT4+subpopulations were only 14%(+/- 11), and the ratio of OKT4+/OKT8+changed from 0.5:1 (in the first week) to 0.18 (in the third week). Two parameters (mode and peak) in the histogram of flow cytometry varied in accordance with the variations of TIL's phenotypes. The results suggested that TILs stimulated by rIL-2 could be enriched predominantly in a single subpopulation (OKT8+), which might be related with their specific effects against tumor growth. PMID- 1291151 TI - [The effects of different lipoproteins on cholesterol metabolism in smooth muscle cells of rabbit aorta]. AB - In the present experiment, M-SMC were cultured from rabbit aorta by an explant method and I-SMC cultured by the explant method from cannulated aortic intima of rabbits, and the effects of LDL, A-LDL, OX-LDL and HDL on the cholesterol metabolism in both types of cells were investigated by using 14C oleic acid as the source of cholesterol re-esteri fication in cells. The results showed that LDL enhanced cholesterol re-esterification in both types of cells and HDL had an opposite effect, A-LDL could increase CE synthesis only in I-SMC, while OX-LDL showed a complex effect on the level of CE in different cells by different concentration. The present experiment has studied the relationship between lipoprotein and cholesterol metabolism in SMC at the level of cell metabolism, and suggests that lipoproteins play a key role in AS. PMID- 1291152 TI - [Localization of fibronectin in atherosclerotic lesions by immunohistochemistry and immunoelectron microscopy]. AB - This paper reports the results of a study on the distribution of fibronectin (FN), its form, character and source in atherosclerotic lesions, using immunohistochemistry (PAP method) and immunoelectron microscopic technique. The results showed that large amounts of FN were localized in fatty streaks, gelatinous lesions and early atherosclerotic plaques. The intima smooth muscle cells in atherosclerotic lesions synthesized more FN, and it is likely that FN represents a new marker of smooth muscle cell modulated from "contractile" to "synthetic" state. With the maturation of atherosclerotic plaque, FN did not fill the whole plaque but was concentrated only in the fibrous cap surface and basocentral part of the atheroma. We also proved that procollagen III peptide (PIIIP) distribution in atherosclerotic plaque was similar to that of FN. PMID- 1291153 TI - [Histopathological and ultrastructural changes in 57 cases of high altitude heart disease]. AB - This paper reports the histopathologic and ultrastructural changes in 37 children and 20 adults with high altitude heart disease. Its clinicopathologic features, diagnostic criteria and differential diagnosis from Ke-shan disease and other heart diseases are discussed. The right heart of 37 children showed hypertrophy and dilatation. Microscopically, necrosis and scarring were found mainly in the right ventricular wall (29/37) and the anterior papillary muscles (29/37) of the right ventricle. The hearts of 20 adults (19 Hans and 1 Tibetan) were enlarged and increased in weight. Heart weight increased to 400-500g in 15 cases, and hypertrophy of both ventricles was seen in 16 cases. Necrosis and scarring were found mainly in the papillary muscles (20:16) and the ventricular walls (11:19) of the left and right ventricles. Electronmicroscopy showed that myofibrils were dissolved or degenerated, mitochondria swelled, endoplasmic reticula dilated and glycogen granules decreased. As regards the pathogenesis, the authors stress the role of chronic hypoxia which causes myocardial damage, and advocate the importance of early diagnosis and treatment. PMID- 1291154 TI - Generation of Minute phenotypes by a transformed antisense ribosomal protein gene. AB - Antisense RNAs have been used for gene interference experiments in many cell types and organisms. However, relatively few experiments have been conducted with antisense genes integrated into the germ line. In Drosophila reduced ribosomal protein (r-protein) gene function has been hypothesized to result in a Minute phenotype. In this report we examine the effects of antisense r-protein 49 expression, a gene known to correspond to a Minute mutation An antisense rp49 gene driven by a strong and inducible promoter was transformed into the Drosophila germ line. Induction of this gene led to the development of flies with weak Minute phenotypes and to the transient arrest of oogenesis. Parameters that may affect the success of antisense gene inactivation are discussed. PMID- 1291155 TI - Broad-complex function during oogenesis in Drosophila melanogaster. AB - The Broad-Complex (BR-C) appears to encode factors that mediate ecdysone effects during the larva-adult transition. The main goal of this study was to gain insight into what roles the BR-C might play during oogenesis. The main findings are as follows. First, as determined by heteroallele studies and clonal analysis, de12 is a somatic line mutation that appears to fall into the broad domain of the BR-C. Second, the de12 mutation is associated with the insertion of the gypsy transposon at position 169.5 (Chao and Guild, Embo J, 1986, 5:143-150) in the BR C domain. In its new context this gypsy element exhibits ovarian-specific activation. Both this gypsy activation and the de12 phenotype are partially suppressible by su(f) and su(Hw). Third, we have identified a set of transcripts that cross-hybridize with BR-C sequence spanning the gypsy insertion site (166 179). There are significant differences in these cross-hybridizing species, both in size and relative abundance, between de12 and its parent strain. Finally we have determined that in de12 there is a premature arrest of chorion gene amplification in the late stages of oogenesis. PMID- 1291156 TI - Sequential up-regulation of thyroid hormone beta receptor, ornithine transcarbamylase, and carbamyl phosphate synthetase mRNAs in the liver of Rana catesbeiana tadpoles during spontaneous and thyroid hormone-induced metamorphosis. AB - During both spontaneous and thyroid hormone (TH)-induced metamorphosis, the Rana catesbeiana tadpole undergoes postembryonic developmental changes in its liver which are necessary for its transition from an ammonotelic larva to a ureotelic adult. Although this transition ultimately results from marked increases in the activities and/or de novo synthesis of the urea cycle enzymes, the precise molecular means by which TH exerts this tissue-specific response are presently unknown. Recent reports, using RNA from whole Xenopus laevis tadpole homogenates and indirect means of measuring TH receptor (TR) mRNAs, suggest a correlation between the up-regulation of TR beta-mRNAs and the general morphological changes occurring during amphibian metamorphosis. To assess whether or not this same relationship exists in a TH-responsive tissue, such as liver, we isolated and characterized a cDNA clone containing the complete nucleotide sequence for a R. catesbeiana urea cycle enzyme, ornithine transcarbamylase (OTC), as well as a genomic clone containing a portion of the hormone-binding domain of a R. catesbeiana TR beta gene. Through use of these homologous sequences and a heterologous cDNA fragment encoding rat carbamyl phosphate synthetase (CPS), we directly determined the relative levels of the TR beta, OTC, and CPS mRNAs in liver from spontaneous and TH-induced tadpoles. Our results establish that TH affects an up-regulation of mRNAs for its own receptor prior to up-regulating CPS and OTC mRNAs. Moreover, results with cultured tadpole liver demonstrate that TH, in the absence of any other hormonal influence, can affect an up-regulation of both the TR beta and OTC mRNAs. PMID- 1291157 TI - Early gene interaction during prepupal expression of Drosophila arginine kinase. AB - Arginine kinase displays a distinctive rise and fall in specific activity and specific protein levels during the prepupal stage of Drosophila development with maximal activity occurring at morphological stage P3. This developmentally regulated peak is under the influence of ecdysone. Altered doses of the major ecdysone-inducible "early" genes at cytological regions 75B and 2B5 alter this pattern of expression while altered doses of another major "early" gene at 74EF have no effect. We hypothesize that a product of the 2B5 locus and a product of the 75B locus interact to effect this developmental pattern of expression of Drosophila arginine kinase. PMID- 1291158 TI - [Diurnal sleep apnea in myotonic dystrophy]. AB - We investigated diurnal sleep apnea in myotonic dystrophy with respiratory inductive plethysmography. Five of eight patients met criteria for sleep apnea syndrome and had central apnea mainly. In a case showing periodic breathing with apnea like Cheyne-Stokes type breathing, the duration of apnea and breath was even and the tidal volume went waxing and waning regularly. In the other four cases, central apneas were observed in sequence, but the duration of apnea and the tidal volume changed variously. Large breaths between apneas elevated arterial oxygen saturation rather than stable breaths without apnea. We suspected that hypoxemia, which exacerbated by involvement of respiratory muscles, supine position and sleep, initiated the hyperventilation between apneas. And then the saturation of oxygen raised by hyperventilation would cause central sleep apnea. PMID- 1291159 TI - [Neurological and neuroimaging studies of eclampsia]. AB - Clinical and neuroimaging studies were made in twenty-one patients during the attack of eclampsia. Most frequent neurological signs and symptoms were the impairment of consciousness, headache, seizure and visual disturbance. Mean arterial blood pressure increased by 46 mmHg (n = 21) during the attacks. Eight of 9 patients studied by CT and/or MRI showed transient abnormalities on brain images during the attack in the occipital cortex, basal ganglia, and internal and external capsule. The findings were compatible with brain edema and were seen mainly in the white matter. Cerebral blood flow measured by SPECT method in one patient during an attack with visual disturbance showed increased blood flow in the occipital cortex. Acute increase in blood pressure, cerebral hyperperfusion and edema, similar to the pathophysiology of hypertensive encephalopathy, were considered to play an important role in the pathogenesis of eclampsia. PMID- 1291160 TI - [The correlation between vertebral artery asymmetry and pontine infarction--an MR angiography study]. AB - The purpose of this study is to evaluate the correlation between variation of the vertebral artery (VA) and the incidence of pontine infarction. A total of 206 patients were examined using magnetic resonance imaging (MRI) and 3-dimension time-of-flight MR angiography (MRA) of the brain. Of these, 54 patients had pontine infarctions (23 symptomatic and 31 asymptomatic), and the majority of them were located in the pontine base. The sites of dominant lesion in the pons were right in 18 cases, left in 8 cases, and bilateral in 28 cases. The number of patients with VA asymmetry (the ratio of internal diameters 1:2 or more) were 89 (43.2%). Of these, 67 patients had small diametric VA of right side, and 22 of left side. Among the 117 patients with normal VA pattern, 19 (16.2%) had infarction, while among the 89 patients with VA asymmetry, 35 (39.3%) had infarction. The patients with small diametric VA of right side significantly had infarctions in the same side of the pons. The results of this study suggest that VA asymmetry is considered to be one of the risk factors of pontine infarction and that MRA can be useful in the examination of the cerebral artery as a valuable and non-invasive screening method. PMID- 1291161 TI - [Adverse effect of antiepileptic drugs on the visual recognition--a contrast sensitivity function study]. AB - Contrast sensitivity function (CSF) was measured in 16 patients (14-60 yr.) with epilepsy to investigate adverse effect of antiepileptic drugs on the central nervous system. Eight patients were treated with phenytoin, while 8 were given polytherapy (phenytoin in combination with phenobarbital, carbamazepine or valproic acid). Thirty-one normal controls (19-59 yr.) were also subjected to this study. Vertical sinusoidal gratings with various spatial frequencies (0.5 20.0 c/deg) were presented on a video monitor. Contrast sensitivity (reciprocal of threshold contrast) was determined at each spatial frequency. CSF of normal subjects showed an inverted U-shaped function against the spatial frequencies with a peak at 6 c/deg (medium size pattern). There was no significant difference in CSF values between normal controls and patients with epilepsy. However, 3 patients with polytherapy showed the significant reduction of contrast threshold. Since these patients did not complain of visual disturbance with normal visual acuity, CSF abnormality was considered as having subclinical visual dysfunction. These results suggest that CSF is useful for evaluating the adverse effect of antiepileptic drugs on the visual recognition, and that polytherapy is responsible for CSF abnormality. Therefore, monotherapy should be scheduled from the onset of therapy. PMID- 1291162 TI - [A case of hemi-hyperhidrosis and non-paralytic pontine exotropia due to brainstem infarction]. AB - A case of hemihyperhidrosis and non-paralytic pontine exotropia due to brainstem infarction is reported. A 55-year-old hypertensive man developed right hemiparesis with slight dysarthria and nausea upon awaking. The right side of his face and right upper limb and trunk to the level of the Th8-9 territory showed hyperhidrosis, which disappeared in a week. Ocular motor examination revealed that during forward gaze with the left eye fixing, the right eye deviated outward. The patient was able to adduct the right eye to midposition with the right eye fixing. Rightward gaze elicited full abduction and right-beating nystagmus of the right eye, but the left eye did not adduct. When he attempted to gaze leftward, both eyes made the full excursion, but saccades were slow in that direction. Convergence was intact. Vertical gaze was full, and he did not show Horner's sign. This ocular sign, non-paralytic pontine exotropia, disappeared three days later. T2-weighted spin echo magnetic resonance imaging disclosed a small lesion with high intensity in the inner side of the left middle pons. This hyperhidrosis was thought to be caused by destruction of inhibitory fibers thermoregulating sweating. These findings suggest that at the level of the middle pons inhibitory fibers descend along the inner side of facilitatory fibers thermoregulating sweating, which are speculated to descend the dorso-lateral part of the pontine tegmentum. These findings also suggest that lesions of non paralytic pontine exotropia may be located in the paramedian pontine reticular formation rostral to the abducens nucleus with ipsilateral medial longitudinal fasciculus lesion, but further investigation is necessary. PMID- 1291163 TI - [A case of pontine hemorrhage showing hemiasomatognosia]. AB - We reported a case of pontine hemorrhage showing hemiasomatognosia. A 74-year old, right-handed man was admitted to our hospital complaining of numbness of left upper and lower extremities. Neurological examination revealed marked disturbance of superficial and deep sensation of left half of his body without hemiparesis and consciousness disturbance. Neuropsychologically, he had experience of having lost the perception of his left upper limb, which was referred to "conscious hemiasomatognosia" by Frederiks. Brain CT and MRI showed a pontine hematoma involving the right medial lemniscus, the right spinothalamic tract and the right medial longitudinal fasciculus. One week after the onset, hemiasomatognosia disappeared with improvement of sensory disturbance. These indicate that this form of hemiasomatognosia may be associated with transient blockage of somesthetic input. PMID- 1291164 TI - [Bezafibrate myopathy in two patients with chronic renal failure]. AB - Case 1, a 60-year-old man and case 2, a 70-year-old man had several year history of chronic renal failure with hypertension and hyperlipidemia due to diabetes mellitus. Treatment of hyperlipidemia was started by oral bezafibrate intake 1,200 mg per day in case 1 and 400 mg per day in case 2 respectively. Three to fourteen days later, both patients noticed symmetrical muscle pain and weakness. Then the symptoms worsened and they were hospitalized. At the time of admission, both patients revealed weakness in the proximal muscles of their upper and lower limbs and the serum creatine kinase and myoglobin levels were remarkably elevated. Myoglobinuria was also noted. Routine light microscopic examination of biopsied quadriceps femoris muscles of two patients showed scattered necrotic muscle fibers, some of which were under phagocytosis. The symptoms of the patients were immediately resolved after the drug was discontinued. Serum concentration of bezafibrate was remarkably elevated during treatment. Thus the diagnosis was established as having bezafibrate induced myopathy and, as far as we know, this is the first report of bezafibrate induced myopathy in Japan. On the basis of the above description, bezafibrate may induce muscle damage if dose is excess over the renal capacity. Extreme caution is warranted when the patient is placed on bezafibrate and has renal dysfunction. Strict dose adjustment is necessary in taking account of renal function to avoid muscle damage including rhabdomyolysis. PMID- 1291165 TI - [A case of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome with spastic paraparesis and severe distal muscle atrophy of lower limbs]. AB - A 16-year-old boy with hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome was reported. He was the second child of first-cousin consanguineous parents. Since childhood, he was mentally retarded and had frequent episodes of vomiting but no unconsciousness attack. Because of progressive gait disturbance since the age of 15, he was admitted to Kyushu University Hospital. Neurological examination revealed mental defect and spastic paraparesis with bilateral positive pathological reflexes. Moreover, severe muscle atrophy and moderate weakness were observed in the distal portion of lower extremities. The diagnosis of HHH syndrome was made by the examination of amino acids in the serum and urine and by the incorporation study of radioactive ornithine into cultured fibroblasts. EMG and nerve biopsy studies suggested that the muscle atrophy seen in this patient was caused by the degeneration of spinal anterior horn cells. Amino acid imbalance, especially elevation of glutamine and glutamic acid in the CSF, may cause dysfunction of neuronal system including anterior horn cells. PMID- 1291166 TI - [A case of multiple sclerosis with intractable hiccups and sleep apnea syndrome]. AB - A 48-year-old female with multiple sclerosis (MS) accompanied by intractable hiccups of over one month' duration and the sleep apnea syndrome was reported. This MS patient had been well controlled until September 16, 1991 when she experienced nausea, vomiting and hiccups. The patient was admitted to Kawasaki Medical School Hospital on October 9, 1991. A physical examination revealed intractable hiccups. T1-weighted MRI showed a low and T2-weighted image disclosed a high signal intensity area in the tegmentum of the medulla oblongata. The intractable hiccups and vomiting improved with intravenous high dose methylprednisolone injection therapy. The following day, she complained of insomnia and her family observed severe snoring and apnea during the night. These symptoms and the results of a breathing monitor were compatible with the sleep apnea syndrome. These symptoms disappeared following the administration of amitriptyline. There have been few reports of the combination of intractable hiccups and the sleep apnea syndrome in MS. The MRI findings suggest that the causative lesion of these symptoms is in the tegmentum of the medulla oblongata. PMID- 1291167 TI - [Action myoclonus in adult Huntington's disease]. AB - In contrast to juvenile rigid form of Huntington's disease (HD) in which myoclonus is often seen, only 5 patients with myoclonus complicating adult HD have been reported. We herein described an adult HD patient who suffered from severe action myoclonus leading to physical disability. To our knowledge, this is the first case report in Japan. The patient, a 32-year-old female with a family history of chorea, developed choreiform movements and mental changes since the age of 24. Subsequently her motor disability has been aggravated by distinctively different involuntary movements characterized by sudden, violent, continuous muscular contractions of four extremities on any attempts at movement. Examination revealed moderate dementia and chorea complicated by frequent myoclonic jerks involving upper and lower extremities in posture or during movement. A head CT scan and MRI revealed caudate atrophy. The myoclonus, as recorded by surface electromyography over the right arm consisted of 40-60 msec synchronous semirhythmic bursts. The cortical component of SEP was enlarged and C reflex was also observed. Clonazepam (4 mg a day) was instituted with a pronounced reduction in myoclonus and a return to her previous level of daily life activity. Although myoclonic jerks are often recognized in juvenile patients with rigid form of HD, they have been considered to exert a minor influence on physical disability. By contrast, our present observation and review of literature suggest that myoclonus may lead to severe motor impairment in adult HD. PMID- 1291168 TI - [A case of transient parkinsonism due to mesencephalic hemorrhage]. AB - A 68-year-old man was admitted because of sudden onset gait disturbance and bradykinesia. He experienced left putaminal bleeding following mild right hemiparesis and emotional incontinence without any difficulties in his daily life since three years before admission. On neurological examination the patient was alert and oriented. He showed forced crying. Myerson's sign was positive. There were no abnormal findings in ocular movements, pupillary reflexes and other cranial nerves. Muscle tone was increased with cog-wheel phenomenon in bilateral upper extremities. Coordination was preserved. He showed severe akinesia and small steppage gait with stooped posture. Freezing phenomenon was observed in initiation of gait and turning. The deep tendon reflexes were increased in the right side with bilateral pathological reflexes. There was no definite weakness and sensory disturbance in all extremities. Brain CT revealed a small high density lesion in the medial side of right cerebral peduncle and a lens-shaped low density lesion in the left putamen. On T1 and T2 weighted images of MRI, right peduncular lesion showed low signal. It extended to the substantia nigra which was partially destructed. His parkinsonism was rapidly improved and completely disappeared within following two weeks. High density lesion of right peduncle on CT also disappeared. We discussed the mechanisms of parkinsonism following unilateral mesencephalic hemorrhage in this patient. PMID- 1291169 TI - [A case of angiotropic lymphoma diagnosed by adrenal biopsy]. AB - We reported the first case of angiotropic lymphoma diagnosed by adrenal biopsy in Japan. Immunohistochemical study and southern blot hybridization analysis proved it to be B-lymphocyte origin. A 61-year-old man with history of mild hypertension and diabetes mellitus was admitted to our department because of recurrent minor stroke. On admission, general physical findings were normal. Laboratory investigations showed an elevated erythrocyte sedimentation rate and increased serum lactic dehydrogenase (LDH) level. The serial computed tomographic (CT) scan of the brain showed multifocal abnormal density lesions in bilateral hemispheres. Magnetic resonance imaging (MRI) of the brain demonstrated multiple lesions of increased signal intensity in the brainstem and bilateral hemispheres. A subsequent CT scan of the abdomen revealed swelling of bilateral adrenal glands. Adrenal biopsy was performed. Biopsy samples showed the intravascular proliferation of malignant lymphoma cells, non-Hodgkin, diffuse large cell type. These cells had the immunophenotype of a B cell lymphoma (reactive with the antileukocyte common antigen, anti-MB-1, anti-MB-2 and anti-MX-pan B, and unreactive with the anti-MT-1, anti-UCHL, anti-Ki, anti-kappa, anti-lambda and antifactor-VIII). Southern blot hybridization analysis showed monoclonal rearrangements of the immunoglobulin heavy-chain gene, which strongly suggested a B-lymphocyte origin. Thus, a diagnosis of angiotropic lymphoma was made. As soon as chemotherapy was begun, the patient fell into deep coma. A repeat CT scan of the brain was normal. His clinical status gradually deteriorated, and he died 18 months after his initial symptom. Autopsy, which was limited to the body, revealed characteristic systemic intravascular stagnation of lymphoma cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291170 TI - [A case of ornithine transcarbamylase deficiency presenting severe symptoms in adulthood]. AB - An adult female case of ornithine transcarbamylase (OTC) deficiency is presented in the following. The patient had had past episodes of drowsiness with a duration less than a few minutes several times a year during childhood. She suddenly became comatose at 25 years of age, and died after 13 months of persistent vegetative state. Blood chemistry showed hyperammonemia with no liver cirrhosis or portal-systemic shunt. Plasma amino acid analysis indicated elevated glutamate and glycine levels, and plasma levels of citrulline and arginine to be low. The urinary orotic acid level was high. OTC activity of a liver specimen was 65 percent of the normal level. This is a rare case demonstrating hyperglycinemia and an elevated level of serum OTC. The importance of ruling out defective ureagenesis in adults with disturbed consciousness should be emphasized. PMID- 1291171 TI - [A case of Machado-Joseph disease--cerebral blood flow and cerebral metabolic rate of oxygen]. AB - A 51-year-old woman, with progressive gait disturbance and dysarthria, had been diagnosed as Menzel-type spinocerebellar degeneration. Later, she developed dystonic posture of upper limbs and bulging eyes. She was diagnosed as Machado Joseph disease from neurological findings, which consisted of cerebellar signs, pyramidal tract signs and extrapyramidal tract signs and peripheral neuropathy. She died suddenly of unknown origin. Her illness lasted about 13 years. Neuropathological findings showed moderate neuronal loss with gliosis in the subthalamic nucleus, globus pallidus, substantia nigra, dentate nucleus, oculomotor and hypoglossal nucleus and anterior horn. Positron emission tomography (PET) using 15O steady state inhalation technique revealed reduction of cerebral blood flow and cerebral metabolic rate of oxygen in not only cerebellum but also cerebral cortex. These findings are different from typical PET findings of spinocerebellar degeneration. PMID- 1291172 TI - [A case of moyamoya-like disease with repetitive TIA on drinking]. AB - We reported here a patient of moyamoya-like disease with repetitive limb-shaking TIAs on drinking. Regional cerebral blood flow (rCBF) was quantified with and without drinking by single photon emission computed tomography with intravenously injected N-isopropyl-p-(I-123) iodoamphetamine (IMP). RCBF was reduced by alcohol ingestion. We speculated that homodynamic TIAs might be caused by impaired autoregulation in the region of the left carotid artery. PMID- 1291173 TI - [A case of neuro-Behcet's disease with hemorrhagic brain stem lesion detected by MRI]. AB - A 45-year-old woman complained of fever, arthralgia and left hemiparesis. She had suffered from recurrent oral aphthous ulcers, genital ulcers, uveitis and erythema nodosum. Laboratory examination demonstrated pleocytosis in the cerebrospinal fluid. MRI showed foci of high signal intensity on the T2-weighted images in the right pontine base, surrounded by a rim of low signal intensity suggestive of small hemorrhages. Following steroid therapy, these symptoms diminished and abnormal findings in brain MRI improved. This MRI findings may be due to hemosiderin deposition at recent stage resulting hemorrhages in foci of acute inflammation stage. We would like to emphasize that MRI are useful to evaluate the lesion of neuro-Behcet's disease and some lesions may behave like hemorrhages. PMID- 1291174 TI - [Divergence paralysis due to a lesion of the lateral tegmentum of the midbrain caused by thalamic hemorrhage]. AB - A 66-year-old diabetic and hypertensive man suddenly developed right hemiplegia. Examination revealed right hemiplegia including his face, vertical gaze palsy, and divergence paralysis. The cranial CT scan disclosed a left thalamic hemorrhage as large as 40 mm in diameter, which extended to the midbrain. He was treated medically and his divergence paralysis improved. But all other symptoms remained for the next 11 months and he eventually died of acute retroperitoneal hemorrhage. The autopsy revealed spongy state and gliosis extending from the left thalamic nuclei to the left midbrain. In the tegmentum, dorsolateral part around the left oculomotor nucleus was involved. The precise location of the human divergence center of the eyes is still unknown. According to previous reports, the divergence center may locate in the tegmentum of the midbrain or pons. Recently, animal experiments detected the neurons which fire for divergent in the mesencephalic reticular formation just dorsal and lateral to the oculomotor nuclei. Our case had a lesion of gliosis and spongy state, namely the old hematoma, in the same portion. Therefore, we considered that the human divergence center of the eyes might exist in the lateral tegmentum of the midbrain, just lateral and dorsal to the oculomotor nucleus. PMID- 1291175 TI - [Adult-onset neuronal ceroid lipofuscinosis--a case report with biological study]. AB - A 32-year-old male was admitted to our hospital complaining of dementia, gait disturbance and blindness. These symptoms developed at the early two decade and were progressive. On admission, his clinical features included dementia (IQ = 69), spasticity, accentuated deep tendon reflexes, ataxia and hypesthesias in his distal limbs. Brain CT scans showed diffuse cerebral atrophy. On light microscopy, many abnormal lipopigments resembling ceroid and lipofuscin were found in Schwann cells of sural nerve and histiocytes of colon. Ultrastructurally, these materials showed lamellar structure like Zebra bodies. Nine lysosomal enzymes, serum very long-chain fatty acids, serum amino acids and urinary oligosaccharides were all normal. Neuronal ceroid lipofuscinosis (NCL) of adult type was diagnosed on the basis of clinical features, radiological and pathological findings, and biochemical studies. Many previous studies suggested that NCL was a disorder with lysosomal dysfunction. We examined lysosomal protein degradation, using 125I-low density lipoprotein (LDL) in cultured fibroblasts from this patient. The degradation of LDL was normal, compared to control subjects. The activities of cathepsin and lysosomal glycosidases, were also normal. The amount of urinary dolichol has been reported to be elevated in the patients with infantile and late infantile types of NCL. However, no elevation was found in the urine of our patient. PMID- 1291176 TI - [Three-dimensional surface display with 123I-IMP in corticobasal degeneration]. AB - A 65-year-old right-handed woman was admitted due to gait disturbance. She had suffered from progressive motor clumsiness in the left-sided limbs for four years. On admission, she was mildly demented, but not aphasic. Neurological examination disclosed constructional disability, limb-kinetic apraxia on the left side, and parkinsonism. Brain CT and MRI showed no responsible lesion. Three dimensional surface display with 123I-IMP demonstrated decreased cerebral blood flow mainly in the right angular gyrus, and mildly in the right central region. She was clinically diagnosed as having corticobasal degeneration. Hypoperfusion in the angular gyrus and central region may account for constructional disability and limb-kinetic apraxia, respectively. Three-dimensional surface display with 123I-IMP appears to be useful for detecting the cortical region. PMID- 1291177 TI - [Small bright spot in hippocampus]. PMID- 1291178 TI - [Amnesia and field CA-1 of the hippocampus]. PMID- 1291179 TI - [Residual cavity of the Ammon's horn: incidental MR finding]. PMID- 1291180 TI - [Small bright signal in the hippocampus on MR: dilated residual cavity of hippocampal sulcus]. PMID- 1291181 TI - [Some problems on the characteristic clinical features and gene linkage analysis of autosomal dominant spinocerebellar degenerations]. PMID- 1291182 TI - Oral lesions in elderly denture wearers. AB - A total of 298 patients in geriatric institutions were surveyed; 62.8% were edentulous. The frequency of denture hyperplasia and of flabby ridge was related to denture quality which deteriorates with irregular dental visits. Denture stomatitis and inflammatory papillary hyperplasia of the palate were related to denture age only and not to quality. All denture-related lesion frequencies increased with patient age and denture age. The total frequency of soft tissue lesions was 16.7% in edentulous non-denture patients and 58.2% in patients with poor quality dentures. The lowest frequency of soft tissue lesions was in edentulous, non-denture patients. Poor oral hygiene increased the frequency of positive cultures for Candida from the dentures. PMID- 1291183 TI - Arizona providers' use and knowledge of fluoride supplements. AB - Dietary fluoride supplements are recommended for dental caries prevention in children without access to optimally fluoridated water. Previous studies have shown deficiencies in dentists' and physicians' knowledge about dietary fluoride supplementation. Data were collected from dentists, physicians and other healthcare provider groups to assess dietary fluoride supplement knowledge and practices. Pediatricians and dentists were found to be the most knowledgeable concerning the recommended prescribing protocols. Substantial proportions of all practitioner groups had insufficient knowledge about the recommended dosages of dietary fluoride supplements by age, fluoride levels in local water supplies, and the effectiveness of fluoride delivery methods. Baseline knowledge and practices were determined for healthcare provider groups within Arizona. PMID- 1291184 TI - Clinical effects of a stannous fluoride mouthrinse on plaque. AB - The purpose of this 3-week, double-blind study was to determine the effect of a stannous fluoride-containing mouthrinse on existing and developing dental plaque. A total of 55 subjects (mean age = 31.42 yrs.) received a professional prophylaxis in randomly assigned contralateral quadrants and were then stratified into two balanced groups based on screening plaque scores: one group (27 subjects) used the placebo rinse, the second group (28 subjects) used the test mouthrinse (0.63% diluted to 0.1% stannous fluoride). Plaque index (PI) and stain index (SI) were scored at baseline, week 1 and week 3. Gingival inflammation (GI) was monitored as a measure of product irritancy potential. The PI for the stannous fluoride rinse was significantly lower than the placebo, (p < 0.0001), for both prophied and unprophied sites with an average reduction of 29% at week 1 and 28% at week 3. There was no statistically significant difference between the presence or absence of prophylaxis. Plaque indexes for both stannous fluoride and placebo showed significant reduction (p < 0.0001) compared to baseline in all sites. Differences in staining potential between stannous fluoride and placebo were not significant (p > 0.05) at any time during the study. The stain index for both stannous fluoride and placebo showed a non-significant increase from baseline in the prophied and unprophied sites. No irritancy was noted, although a trend towards lower GI scores was observed at 3 weeks for the stannous fluoride group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291185 TI - Remineralizing potential, antiplaque and antigingivitis effects of xylitol and sorbitol sweetened chewing gum. AB - The objective of this study was to investigate the effects of xylitol and sorbitol sweetened chewing gums on plaque accumulation, gingival inflammation and remineralizing potential of plaque following six weeks of use. Twenty-eight consenting individuals were randomly assigned to each of three phases (six weeks in duration) consisting of chewing xylitol gum, chewing sorbitol gum and a non chewing phase. Subjects chewed one stick after every meal and at two other times for a total of five sticks per day. At the completion of each treatment phase, plaque and gingival indexes were performed and plaque was later collected. Calcium concentration in plaque was determined by atomic absorption spectophotometry. Reductions in plaque indexes were significant for both xylitol gum (p < 0.001) and sorbitol gum (p < 0.05) when compared to the no chewing period. The gingival indexes reflected a decrement in gingival inflammation with both xylitol and sorbitol, though only sorbitol values were statistically significant (p < 0.05). Chewing xylitol and sorbitol gums reduced plaque accumulation and gingival inflammation. In addition, both gums enhanced the remineralization potential of plaque. Xylitol gum showed a superior effect with respect to remineralization potential and plaque reduction. Sorbitol gum had a superior effect on gingival health but not significantly so. PMID- 1291186 TI - Non-invasive 27-hour blood pressure registration including dental checkups in some dental practices. AB - The study involved 53 patients aged 18 to 67 (mean age 38.8, SD 13.6), 26 male and 27 female, who were monitored by means of a 27-hour non-invasive ambulant blood pressure registration, using the Oxford Monitoring System. All patients had been under dental supervision by the same dentist for more than one year, and were familiar with the procedure during checkups. This study showed a significant rise in systolic blood pressure (8.6 mmHg) and a tendency towards increased diastolic pressure (2.9 mmHg) during dental checkups in comparison with the values recorded 24 hours earlier during normal daily activity. These results were independent of the blood pressure classification (normotensive, borderline or hypertensive) of the patients and are comparable to the increases measured during a visit to the GP. Neither the sex nor the manner of the dentist had any significant influence on either the systolic or diastolic pressure values during the checkup. Nor did the phobic level of the patients significantly influence blood pressure values during the dental checkup. On the basis of the results of this study, it may be concluded that regardless of whether the patient is phobic or non-phobic, and regardless of the sex and manner of the dentist, blood pressure measurements taken during dental checkups are reliable and can be used for referral decisions. PMID- 1291188 TI - Developing the new faculty member. PMID- 1291187 TI - A class of their own. PMID- 1291189 TI - Catch a Tsunami to Hawaii. Practice in paradise for UOP grads. PMID- 1291190 TI - A quarter century of giving. The P&S Club turns twenty-five. PMID- 1291191 TI - Access to dental care: UOP responds. PMID- 1291192 TI - Masters at their specialty. PMID- 1291193 TI - Coming soon to an office near you! PMID- 1291194 TI - Reacting to the future. PMID- 1291195 TI - Aortic dissection and aortic aneurysm surgery: clinical observations, experimental investigations, and statistical analyses. Part II. PMID- 1291196 TI - In vivo effect of cis- and trans-diamminedichloroplatinum(II) on DNA and chromatin degradation in Ehrlich ascites tumour cells. AB - Ehrlich ascites tumour (EAT) cell nuclei were isolated from mice treated with cis and trans-diamminedichloroplatinum(II) (DDP). The electrophoretic analysis of DNA extracted from corresponding nuclei revealed the high level of EAT DNA stability suggesting very low DNA endonuclease activity. The DNA degradation to high molecular weight fragments was achieved by mild treatment of nuclei with exonuclease DNase I. Cis- and trans-DDP reduced the rate of EAT DNA breakdown to high molecular weight fragments. Direct gel electrophoresis of the same nuclei confirm and extend our recent finding of rat liver chromatin breakdown to large chromatin blocks of uniform size. PMID- 1291197 TI - Drug treatment of ventricular arrhythmia. PMID- 1291198 TI - Erythrocyte membrane lipid composition fluidity in patients with essential hypertension. AB - The lipid composition and fluidity of erythrocyte membrane in 36 patients with essential hypertension were examined. The results showed that either cholesterol/phospholipid molar ratio or lipid peroxides content was significantly increased (P < 0.01 or 0.001), and the superoxide dismutase activity, contents of four classes of phospholipids, i.e., phosphatidyl ethanolamine, phosphatidylcholine, phosphatidylserine and sphingomyelin of erythrocyte membrane, and lipid fluidity were significantly decreased (P < 0.05, < 0.01 or < 0.001) as compared with those in 35 normotensive control subjects. These results suggested that the changes of lipid composition and fluidity might associate with the decreased activities of cation transport systems in cell membranes and play an important role in the pathogenesis of essential hypertension. PMID- 1291199 TI - Evaluation of the effect of PTCR/PTCA by 99mTc-MIBI myocardial imaging in acute and old myocardial infarction. AB - This study is to clarify the ability of technetium-99m-Hexakis-2-methoxyisobutyl isonitrile(MIBI) myocardial scintigraphy for assessment of the effect of PTCR/PTCA as compared with conventional thallium-201 myocardial scintigraphy (201Tl). 99mTc-MIBI (740-888MBq) was injected before emergency PTCR/PTCA, and the initial imaging was performed immediately after PTCR/PTCA in 4 patients with acute myocardial infarction (AMI). On the other hand, in 2 patients with old myocardial infarction (OMI), 201Tl and MIBI myocardial imagings were performed before and one week after rescue PTCA. The defect area on the follow-up MIBI imaging was smaller than that on the initial MIBI imaging in 2 patients with successful emergency PTCR/PTCA. But in the other 2 AMI patients with unsuccessful reperfusion, the defect area did not significantly decrease after PTCR/PTCA. Reperfusion was successful in one of the two patients with OMI. In both the two patients with OMI, the MIBI defect area did not significantly decrease after rescue PTCA. MIBI myocardial scintigraphy is a useful noninvasive method for evaluating the effect of emergency PTCR/PTCA for myocardial salvage in patients with AMI, because MIBI is a kit type agent, and it does not redistribute. PMID- 1291200 TI - Vitamin D and calcium metabolism in children with nephrotic syndrome of normal renal function. AB - This study demonstrates that there are distinct abnormalities of vitamin D and calcium metabolism in children with nephrotic syndrome (NS) and normal renal function. In patients with active NS, serum calcium, ionized calcium, 25-OHD3 and CT were decreased, plasma PTH level was increased and serum ALP was elevated. These abnormalities returned to normal in remission. Serum 1,25-(OH)2D3, although normal in absolute value during both active and remission stage, may be inappropriately low for the hypocalcemia and hyperparathyroidism during the active stage. Therefore, children with active NS are at the risk of developing metabolic bone disease. The treatment with a high dose of vitamin D3 may correct the abnormalities, which suggests vitamin D3 should be used in children with protracted active NS. PMID- 1291201 TI - Protective effect of Re-LPS antiserum on experimental multiple system organ failure. AB - This study examines the possible beneficial effect of Re-LPS (F515) antiserum on experimental multiple system organ failure (MSOF) in rabbits. The results showed that the plasma LPS level was significantly decreased, and it took a shorter period to clear up LPS in experimental than in control rabbits after receiving Re LPS antiserum. Pretreatment with antiserum can markedly improve the function of the liver, lungs, kidneys, blood and gastrointestinal tract. The MSOF incidence in the group of rabbits receiving immune sera was only 11.2% and the survival rate was raised by about 40.0%. The results suggest that early passive immunotherapy may neutralize gut-derived endotoxin, inhibit endotoxin-induced mediators release and prevent development of severe complications due to sepsis. It is therefore postulated that LPS core antiserum may provide a prophylactic effect on the development of experimental MSOF. PMID- 1291202 TI - A study on a family with high incidence of leukemia. AB - A family with a high incidence of leukemia was investigated and followed up for 10 years. Up to now, 7 of 48 members in this family had acute nonlymphocytic leukemia. Chromosomal aberration was found in 3 healthy members, 2 of whom were found to have 47, XX, +5, -8, +Mar, del (7) (q22-qter) and 45, XO, -Y chromosomes and developed this disease 5 and 7 years later respectively. Pedigree analysis suggested that the hereditary defect in the family should rest on the maternal lineage. It is considered that hereditary factors play an important part in the pathogenesis of leukemia in the family. PMID- 1291203 TI - Growth promoting effect of zinc supplementation in infants of high-risk pregnancies. AB - This study was made to determine whether zinc deficiency is one of the factors involved in growth retardation of infants of high-risk pregnancies. The high risk factors were hypertension of pregnancy, diabetes mellitus, congenital heart disease, chronic nephritis, rheumatic heart disease and hyperthyroidism. 102 neonatal infants were divided into 3 groups: breast fed group, 37 cases; test group, 32 cases formula-fed with supplementary zinc 1.14-2.28 mg/kg/d; and control group, 33 cases formula-fed and supplemented with Vitamin B complex as placebo. The groups were divided by double-blind and randomized method. There were no differences in the 3 groups in sex ratio, growth status and serum zinc concentration at the beginning of the study. Anthropometric data were obtained at 0, 3 and 6 months. PMID- 1291204 TI - Iliac periosteal graft with vascular pedicle in the treatment of avascular necrosis of the femoral head. Experimental study and clinical application. AB - From March 1983 to June 1987, 6 patients with avascular necrosis of the femoral head were treated with vascular pedicled iliac periosteum graft. Follow-up for 3 to 7.5 years showed satisfactory results. The patients experienced no hip pain, could walk freely, and resumed work after the treatment. X-ray films showed that the original defect of the femoral head was filled up and its outline was clear and smooth. The bone density of the femoral head and neck normalized. The experimental study indicated that the vascularized periosteum improves the blood supply and initiates the revascularization and osteogenesis of the femoral head. The authors conclude that the technique is suitable for the treatment of avascular necrosis of the femoral head of Stage II and III. PMID- 1291205 TI - DNA-malignancy-grading of bladder tumor and its clinical significance. AB - The DNA-Malignancy-Grade(DNA-MG) of paraffin-embedded tumor specimens from 38 patients with bladder tumor was determined by image cytometry. A good correlation was found of DNA-MG with clinical staging and histopathological grading. The DNA MG of T1 and G1 bladder tumor was less than 3.00, while that of T3-4 and G3 bladder tumor was greater than 3.00. The 5-year survival of patients with DNA-MG < 3.00 and > 3.00 was 100% and 36.9%, respectively. The data indicate that DNA-MG plays an important role in the assessment of the prognosis and the planning of treatment. PMID- 1291206 TI - Neuroarthropathy. Clinico-radiologic analysis of 115 cases. AB - 115 patients (163 joints) with neuroarthropathy (Charcot joint) were observed clinically and radiologically. In Charcot joint of the shoulder, the entire scapula was disintegrated. After debridement and arthrodesis, fragmentation of bone reappeared at both ends of the affected long bone and even on the lateral surface of diaphysis. Fragmentation of the articular surface and the subchondral bone was seen in the non-weight-bearing surface. 32 patients in this series sustained spontaneous fractures without a history of trauma or undue strain. Follow-up for short periods (2 to 6 weeks) showed rapid progressive destruction. These results indicated that neurotrophic theory seems to furnish an explanation for the pathogenesis of the Charcot joint, and that bone resorption should be the primary change while bone hypertrophy and proliferation, the secondary. PMID- 1291207 TI - Imaging study of lumbar posterior marginal intraosseous node. An analysis of 36 cases. AB - Clinical, radiological and CT manifestations of 36 patients with lumbar posterior marginal intraosseous cartilaginous node (LPMN) were analysed. Of the 36 patients, 27 were male and 9 female, most of them were young adults. The posteroinferior margin of L4 was the commonest site and the posterosuperior margin might also be involved. Two patients had multiple lesions. Typical radiological findings included a defect in the posteroinferior (or posterosuperior) margin of the affected vertebral body and behind the defect a bony ridge protruding into the spinal canal. CT scan showed a cartilaginous node in the posterior zone of the vertebral plate. It is suggested that LPMN was the result of disc material herniating into the posterior aspect of vertebral body through ruptured cartilaginous end-plate during the adolescence, similar to that of the limbus vertebra. Hyperflexion and hyperextension of the spine probably play an important role in the pathogenesis. The existence of LPMN favours posterior disc herniation in the same disco-vertebral junction. PMID- 1291209 TI - Trends in cerebrovascular mortality in the period 1950-1987. PMID- 1291208 TI - Ischemic stroke treated with Ligusticum chuanxiong. AB - Ligusticum Chuanxiong and its effective components were studied in the treatment of ischemic stroke, a common emergent disease in China. Some injections of the medicines, including Ligusticum, Ligustrazine, Ligustylid and ferulic acid, were tested clinically and experimentally. The results showed that the effects of the drugs were the same as or even better than those of the controls, such as papaverine, dextran and aspirin-persantin. They could improve brain microcirculation through inhibiting thrombus formation and platelet aggregation as well as blood viscosity. PMID- 1291210 TI - Glucagonoma syndrome. PMID- 1291211 TI - [Delivered by direct intrauterine transfer of gametes]. AB - A nurse, 27, primary sterility for 5 years with normal pelvic findings. Hysterosalpingogram showed right tube not visualized, and impatent, left tube with slight enlargement at ampulla. Her last menstrual period was September 5, 1991. Ovaries hyperstimulated by clomiphene, HMG and hCG, and 8 ova taken through vaginal aspiration under B scanning on September 19, 1991. Ova and washed sperms were directly introduced into uterine cavity simultaneously. It turned out to be a successful clinical pregnancy, carried on smoothly up to 36(+1) weeks. She spontaneously delivered a healthy male infant weight 2250 grams on May 15, 1992. PMID- 1291212 TI - [Transcervical resection of endometrium in women with dysfunctional uterine bleeding]. AB - Transcervical resection of endometrium was performed in 65 cases by endoscopic continuous flow resectoscope under epidural anesthesia and B ultrasonic monitoring to treat dysfunctional uterine bleeding which had been treated by conservative measures no avail. Resected tissue included functional and basal layers of endometrium as well as underlying 1-2 mm myometrium. Bleeding immediately after the operation was rare serious followed by watery discharge usually persisted for about 4 weeks. Follow-up examination for 5-20 months showed that 19 cases had amenorrhea, 12 cases spotting, 31 cases had obvious reduced menstrual flow and 3 cases no improvement. Hysteroscopic examination and hysterography in all 24 cases showed no adhesions. This operation involves no abdominal incision and is therefore less traumatic. It is associated with very little bleeding and minimal morbidity. No long term effects on ovarian function was noticed. Endoscopic surgery will probably replace most conventional hysterectomies done for dysfunctional uterine bleeding. PMID- 1291213 TI - [Prognosis of dysfunctional uterine bleeding at puberty]. AB - The factors related to the prognosis of dysfunctional uterine bleeding (DUB) at puberty were analysed according to the 2 to 15 years' follow-up examination in 44 cases of pubescent DUB. It was found that the establishment of a regular menstrual cycle depends on the duration of disease. Among 19 cases who established a regular cycle, 12 cases (63.2%), 6 cases (31.2%), 1 case (5.3%) with the duration of disease < or = 4 years, 5 to 10 years, and > or = 11 years respectively. The incidence of gynecologic morbidity of pubescent DUB as referred to transfusion, dilatation and curettage, hysterectomy and polycystic ovarian disease was 19/44, 12/44, 1/44 and 5/44 respectively. Of 30 married patients 28 desired children and four of them conceived spontaneously. 9 cases (37.5%) conceived after ovulation induction. It is suggested that the pubescent DUB should be defined as the onset of DUB occurs within 2 years after menarche. Close following up and timely treatment contribute much to the control of the disease and decrease of gynecologic/morbidity. PMID- 1291214 TI - [Diagnostic errors in dysfunctional uterine bleeding. Analysis of 24 cases]. AB - This paper reports 24 cases of genital organic diseases which were misdiagnosed as dysfunctional uterine bleeding during 1984-1990. These include small submucous uterine myoma 5 cases, Granulosa cell tumor of ovary 2 cases, leiomyosarcoma of uterus 1 case, ectopic pregnancy 7 cases, carcinoma of endometrium 4 cases, abortion 3 cases, choriocarcinoma 2 cases, altogether there were 9 patients with malignant tumors in the series. The author point out that it is possible to reduce the misdiagnosis rate by emphasizing history, diagnostic curettage, ultrasonography, hysteroscopy and blood hCG determination. PMID- 1291215 TI - [Immunopathological study on the uterine spiral arteries in pregnancy-induced hypertension]. AB - The uterine spiral arteries were studied by the immunohistochemical ABC method in 30 cases of Pregnancy Induced Hypertension (PIH) and 10 cases of normal pregnant women. Depositions of IgM and/or C3 on the vessel wall were significantly observed only in PIH cases (15 cases, 50.0%; P < 0.05). Depositions of IgG were seen in 5 cases of PIH 16.7% showing significantly decrease. (P < 0.001), as compared with the normal pregnant women (9 cases, 90.0%). The results suggest that PIH is related to chronic rejection reaction resulting possibly from the decrease of local immunosuppression in pregnancy. Meanwhile the positive stain of IgG, IgM and C3 seen in the nuclei of decidual cells in some of PIH cases were discussed. PMID- 1291217 TI - [The significance of pathological examination of the placenta in exploring the causes of intrauterine fetal death]. AB - The results of pathological examination of 68 placental from intrauterine fetal death during 1982. 4-1989.12 is presented. The shortest time interval between the death of the fetus and the expulsion of the placenta was 14 hours, and the longest was 1 month. The pathological findings may be divided into 5 classes: trophoblastic; stromal; villous net; cord and others. Causes of fetal death could be identified in 65 cases (96%), in which 36 cases (53%) were due to the factors of placenta and its appendix. It was suggested that the pathological examination of placenta might give the clue to the cause of fetal demise. PMID- 1291216 TI - [Pathological and clinical study on 80 cases of liver disease in pregnancy]. AB - Ninety-seven cases of liver disease in pregnancy confirmed by pathological examination were studied. The results showed that in addition to virus hepatitis (58.8%), which was the leading cause, there were quite a proportion of other liver diseases. Among these acute fatty liver of pregnancy accounted for 18.6%, intrahepatic cholestasis of pregnancy were 16.5%. The causes of misdiagnosis and the bases for differential diagnosis were discussed. It was considered that early pathological examination of liver and other morphological study were important in diagnosis of liver diseases in pregnancy. PMID- 1291218 TI - [Relation between placental morphometry and fetal growth]. AB - Forty-eight placentae of full term infants, 21 placentae from appropriate for gestational age infants (AGA) and 27 placentae from small for gestational age infants (SGA) were measured by morphometric technic using the automatic image analyzer, in order to find out the extent of fetomaternal exchange which determines the transfer of oxygen and nutrition from mother to fetus and fetal growth. The results of measurement correlated well both with infant birth weight and placental weight. They demonstrated striking quantitative differences when the placentae of SGA were compared with those of AGA. The placenta weights in the group of SGA were notably less than those in the group of AGA. It seems that low birth weight relates to low functional tissue mass of placenta. This reduction of functional tissue is accompanied by diminution of the area for exchange between mother and fetus, both at the villous surface area and at fetal capillary surface area. Thus, the ability of transferring oxygen and nutrition from mother to fetus is curtailed. The results show that the rate of fetal growth is limited by placental function as well as its weight. PMID- 1291219 TI - [Mechanism and effect of anisodamine on uteroplacental circulation in pregnancy induced hypertension]. AB - The short term effect of anisodamine, an alkaloid isolated from the chinese herb anisodas tonguticus, on blood flow of uterine and umbilical arteries in 16 pregnant women with pregnancy-induced hypertension (PIH) was investigated by means of pulsed doppler ultrasound technique Results have shown that anisodamine could decrease the A/B ratio, resistant index (RI), and pulsative index (PI) of blood velocity in these arteries with statistical significant difference. Its mechanism of action might be the improving of the rheology in PIH and adjusting the imbalance of TXA2/PGI2. It was suggested that the resistance in uteroplacental circulation was decreased and its perfusion improved, so that favors the fetal growth and development. PMID- 1291220 TI - [Clinical analysis of 60 cases of pregnancy with thrombocytopenia]. AB - Sixty cases of pregnancy with thrombocytopenia were analyzed. Bleeding syndrome was found in 36 patients during pregnancy, with 7 cases suffering from massive hemorrhage during delivery and a postpartum hemorrhage rate of 11.7%. There was a negative correlation between the platelet level and the amount of bleeding during gestation and delivery. We suggest that cortico steroid is necessary with a platelet count less than 50 x 10(9)/L in the middle or late trimester of pregnancy to reduce the bleeding tendency during delivery, as well as the incidence of thrombocytopenia in the newborn infant use of excessive platelet transfusion is not encouraged, since it implicates an increase in antibody induction (PAIG) and probability of C type hepatitis in the recipient. Platelet transfusion should be reserved only for the treatment of serious hemorrhage. There were 53 newborn infants, 7 of whom (13.2%) suffered from thrombocytopenia, with a mortality of 1.9% (7/53) during the perinatal. PMID- 1291221 TI - [Carcinoma of the cervical stump. Clinic analysis of 10 cases]. AB - Ten cases of carcinoma of the cervical stumps from Jan. 1965 to Dec. 1990 were analysed. All of the patients received subtotal hysterectomy because majority of patients suffered from benign uterine tumors except one case of ovarian cystadenocarcinoma. The age range of the patients was 40-65 years old. The stump carcinoma was discovered 2-18 years later after primary operations. The average duration was 10.3 years. Only one patient died of 2 years after treatment, remaining patients have good health by surgical and radiotherapy. The authors emphasize that the key to prevent the cervical stump carcinoma is to avoid missing diagnoses of the precancerous lesion and cancer of the cervix, and to closely follow-up the patients with the stumps. PMID- 1291222 TI - [Radionuclide 13m in scanning pelvic congestion syndrome after tubal ligation]. AB - Here are reported 83 cases with pelvic congestion syndrome after tubal ligation. Radionuclide 113m in blood-pool scanning was found to be a valuable method in detecting this syndrome in 72 cases who were proved by operation with a correct diagnosis rate of 98.6%. The mild cases received non-operative treatment. The relationship between the modalities of tubal ligation and this syndrome was discussed and preventive measures suggested. PMID- 1291223 TI - [Lymphatic metastasis of ovarian cancer and extraction of retroperitoneal lymphadenectomy]. PMID- 1291224 TI - Meiotic chromosome distribution in Drosophila oocytes: roles of two kinesin related proteins. AB - Recent new information regarding the proteins required for proper distribution of chromosomes in meiosis has come from studies of Drosophila mutants. These studies reveal that proteins related to the microtubule motor protein, kinesin, function in meiotic chromosome segregation in Drosophila females. The two proteins identified thus far are likely to play very different roles in the process. The ncd protein is a spindle motor in meiosis but may perform a different role in the early mitotic divisions of the embryo. nod functions earlier in meiosis than ncd, prior to the meiotic divisions, and may be either chromosome or spindle associated. The identification of nod as a kinesin protein raises new questions regarding the distributive model of meiotic chromosome segregation. PMID- 1291225 TI - Replication forks are not found in a Drosophila minichromosome demonstrating a gradient of polytenization. AB - Differential DNA replication is widely held to influence polytene chromosome structure by causing the dramatic reductions in heterochromatic DNA content that are characteristic of most endopolyploid cells. The "underreplication model" of heterochromatic sequence underrepresentation predicts that replication intermediates should populate regions of DNA between fully polytenized euchromatic sequences and underpolytenized heterochromatic sequences. We directly tested this prediction using Dp1187, a 1300 kb Drosophila minichromosome containing well-defined heterochromatic regions. DNA from a euchromatic/heterochromatic junction region of Dp1187, demonstrating a significant gradient of underrepresentation in larval salivary glands, lacked the stalled replication forks predicted by the underreplication model. We consider an alternative mechanism leading to heterochromatic sequence underrepresentation involving a process of DNA elimination. PMID- 1291226 TI - Effects of deletions on mitotic stability of the paternal-sex-ratio (PSR) chromosome from Nasonia. AB - Paternal-Sex-Ratio (PSR) is a B chromosome that causes all-male offspring in the parasitoid wasp Nasonia vitripennis. It is only transmitted via sperm of carrier males and destroys the other paternal chromosomes during the first mitotic division of the fertilized egg. Because of haplodiploidy, the effect of PSR is to convert diploid (female) eggs into haploid eggs that develop into PSR-bearing males. The PSR chromosome was previously found to contain several families of repetitive DNA, which appear to be present in local blocks. PSR chromosomes with irradiation-induced deletions have decreased rates of transmission and increased variation in transmission. This study investigates whether these differences in transmission of deletion chromosomes are due to mitotic instability. Two deletion chromosomes (E306 and F316) and the wild-type PSR chromosome were examined. A cytogenetic assay of testes revealed that wild-type PSR males contained the chromosome in 98%-100% of their spermatocytes. Similar counts from carriers of two deletion chromosomes were lower and varied between individuals from 50%-100%. One F316 male did not contain the chromosome in any of its spermatocytes although the chromosome was present in somatic tissues based on hybridization to PSR specific repetitive DNA. A molecular analysis of males found the wild-type PSR chromosome to be present in all somatic tissues. Tissue specific differences in the presence of PSR were found in several males from the two deletion lines. The results show that deletions can result in mosaicism due to increased mitotic instability of PSR. Such individuals sometimes partially or completely fail to transmit the chromosome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291227 TI - A repetitive DNA element, associated with telomeric sequences in Drosophila melanogaster, contains open reading frames. AB - He-T sequences are a complex repetitive family of DNA sequences in Drosophila that are associated with telomeric regions, pericentromeric heterochromatin, and the Y chromosome. A component of the He-T family containing open reading frames (ORFs) is described. These ORF-containing elements within the He-T family are designated T-elements, since hybridization in situ with the polytene salivary gland chromosomes results in detectable signal exclusively at the chromosome tips. One T-element that has been sequenced includes ORFs of 1,428 and 1,614 bp. The ORFs are overlapping but one nucleotide out of frame with respect to each other. The longer ORF contains cysteine-histidine motifs strongly resembling nucleic acid binding domains of gag-like proteins, and the overall organization of the T-element ORFs is reminiscent of LINE elements. The T-elements are transcribed and appear to be conserved in Drosophila species related to D. melanogaster. The results suggest that T-elements may play a role in the structure and/or function of telomeres. PMID- 1291228 TI - Sensitive period for the induction of endoreduplication by rotenone in cultured Chinese hamster cells. AB - Rotenone-induced endoreduplication was investigated in Chinese hamster CHL cells. Cell cycle analyses, using 5-bromo-2'-deoxyuridine (BrdU) labeling, revealed that endoreduplication was induced between the G2-phase and mitotic metaphase. Morphological studies indicated that the chromosomes of cells in metaphase at the time of rotenone exposure immediately aggregated. Within 1 h, however, the aggregated chromosomes began to decondense forming telophase nuclei. Cells with aggregated chromosomes were collected by mitotic selection using the mitotic arrestant TN-16 and then cultured for 30 h following rotenone administration. This population of cells demonstrated an extremely high frequency of endoreduplicated metaphases. Further analysis by BrdU labeling indicated that the aggregated metaphases underwent only one round of DNA replication before endoreduplicated metaphases were formed. The most sensitive period for the induction of endoreduplication by rotenone occurs during mitotic metaphase. PMID- 1291229 TI - Characterization of a new repetitive sequence that is enriched on microchromosomes of turkey. AB - We cloned and characterized a new highly repetitive, species-specific DNA sequence from turkey (Meleagris gallopavo). This repeat family, which accounts for approximately 5% of the turkey genome, consists of a 41 bp repeated element that is present in tandem arrays longer than 23 kb. In situ hybridization to turkey metaphase chromosomes (2n = 80) demonstrated that this sequence was located primarily on certain microchromosomes: approximately one-third of the 66 microchromosomes showed a positive signal. With respect to the macrochromosomes, hybridization was seen only in a pericentric position on nos. 2 and 3. The turkey microchromosome (TM) sequence shares motifs (alternating A3-5 and T3-5 clusters separated by 6-8 bp) that have been found previously in other avian tandemly repeated elements, e.g. a chicken microchromosomes sequence, and W (female) chromosome-specific sequences of chicken and turkey. However, the TM sequence does not cross-hybridize under moderately stringent conditions with these other sequences. The spread and amplification of related repetitive sequence elements on microchromosomes and W chromosomes is discussed. PMID- 1291230 TI - The complex for replication initiation of Escherichia coli. AB - We probed the complex between oriC and DnaA protein using two types of mutants in oriC. Base changes in the DnaA binding sites, DnaA boxes, had little effect on origin function. Mutations which change the distance between DnaA boxes R3 and R4, on the other hand, inactivated oriC unless the mutation deleted or inserted one complete helical turn. Origins with other 10 base pair insertions in the interval between DnaA boxes R2 and R3 were functional, but not insertions in the R1-R2 interval. FIS protein binds to a bipartite site in oriC between DnaA boxes R2 and R3. A model for the oriC/DnaA complex based on these results suggests an array of DnaA monomers with a 34 A spacing upon which oriC is arranged. PMID- 1291231 TI - Control of DNA synthesis genes in budding yeast: involvement of the transcriptional modulator MOT1 in the expression of the DNA polymerase alpha gene. AB - Periodic transcription during the cell cycle of the budding yeast DNA polymerase alpha gene (POL1) requires the cis-acting element 5' ACGCGT 3', which has been found in the 5' non-coding region of all the DNA synthesis genes analyzed so far. Search for trans-acting mutations affecting POL1 expression led to the isolation of the temperature-sensitive reg1033 mutant, that showed increased levels of both DNA polymerase alpha and delta gene transcripts. Cloning of the REG1033 gene demonstrated that it is essential for cell viability and required for proper expression of the POL1 gene. DNA sequence comparison established that the REG1033 gene is identical to MOT1, a gene encoding a presumptive DNA helicase which modulates transcription of several yeast genes. PMID- 1291232 TI - Protein affinity chromatography reveals cell cycle dependent association of cellular factors with human DNA polymerase alpha. AB - DNA polymerase alpha/primase (Pol alpha) is the key replication enzyme in eukaryotic cells. This enzyme synthesizes and elongates short RNA primers at an unwound origin of replication. Pol alpha was used as an affinity ligand to identify cellular replication factors interacting with it. Protein complexes between Pol alpha and cellular factors were analyzed by co-immunoprecipitations with monoclonal antibodies directed against Pol alpha and by protein affinity chromatography of cell extracts derived from pure G1- and S-phase cell populations on Pol alpha affinity columns. Co-immunoprecipitations resulted in the identification of a polypeptide with a molecular weight of 46 kDa. For Pol alpha affinity chromatography, the ligand was purified from insect cells infected with a recombinant baculovirus encoding the catalytic subunit (p180) of Pol alpha (Copeland and Wang, 1991). With 5 x 10(8) infected Sf9 cells, a rapid one step purification protocol was used which yielded in five hours 0.6 mg pure enzyme with a specific activity of 140,000 units/mg. The G1- and S-phase cell populations were generated by block, release and counterflow centrifugal elutriation of exponentially growing human MANCA cells. Starting with 2 x 10(9) non synchronous cells, 5 x 10(8) G1-phase cells were isolated. Chromatography of cell extracts derived from G1- or S-phase cells on Pol alpha affinity columns resulted in identifying several polypeptides in the range of 40-70 kDa. Some of these polypeptides are more abundant in eluates derived from S-phase extracts than from G1-phase extracts. PMID- 1291233 TI - Structural and functional relationships of human DNA polymerases. AB - A continuing theme of our laboratory has been the understanding of human DNA polymerases at the structural level. We have purified DNA polymerases delta, epsilon and alpha from human placenta. Monoclonal antibodies to these polymerases were isolated and used as tools to study their immunochemical relationships. These studies have shown that while DNA polymerases delta, epsilon and alpha are discrete proteins, they must share common structural features by virtue of the ability of several of our monoclonal antibodies to exhibit cross-reactivity. A second approach we have taken is the molecular cloning of human DNA polymerase delta and epsilon. We have cloned the DNA polymerase delta cDNA, and this has allowed us to compare its primary structure to those of human polymerase alpha and other members of this polymerase family. Multiple sequence alignments have revealed that human DNA polymerase delta is also closely related to the herpes virus family of DNA polymerases. In situ hybridization has shown that the human DNA polymerase delta gene is localized to chromosome 19 q13.3-q13.4. In order to further determine the functional regions of the DNA polymerase delta structure we are currently expressing human pol delta in E. coli and baculovirus systems. Other work in our laboratory is directed toward examining the expression of DNA polymerase delta during the cell cycle. PMID- 1291234 TI - Expression of the catalytic subunits of pol alpha and pol delta from fission yeast Schizosaccharomyces pombe. AB - This paper reports on expression and posttranslational modifications of the catalytic subunits of pol alpha and pol delta from fission yeast Schizosaccharomyces pombe. Okadaic acid treatment of S. pombe spheroplasts in amounts known to inhibit phosphatases 1 and 2A resulted in decreased proteolysis of both pol alpha and pol delta. Computer analysis of pol alpha and pol delta sequences confirmed the presence of consensus motifs for protein phosphorylation. Indirect immunofluorescence microscopy of S. pombe cells showed nuclear location of both proteins in wild type cells. However, whereas cells transformed with a vector expressing pol alpha produced a clear increase of the nuclear signal, no increase was detectable in cells transformed with pol delta. This observation suggests the existence of a mechanism limiting the cell concentration of pol delta in the cell. Constitutive expression of S. pombe pol delta in E. coli was possible only with vectors containing truncated forms of its gene, indicating a toxic effect of pol delta on E. coli growth. PMID- 1291235 TI - Roles of POL3, POL2 and PMS1 genes in maintaining accurate DNA replication. PMID- 1291236 TI - Use of non-denaturing Southern hybridization and two dimensional agarose gels to detect putative intermediates in telomere replication in Saccharomyces cerevisiae. AB - Telomeres are required for the complete duplication of the ends of linear chromosomes. Saccharomyces telomeres bear approximately 350 bps of C1-3A/TG1-3 sequences. Previous work using non-denaturing Southern blotting has demonstrated the cell cycle controlled appearance of single stranded TG1-3 tails on chromosomal and plasmid telomeres (Wellinger et al. submitted). Furthermore it was shown that short linear plasmids carrying an origin of replication derived from 2 microns DNA can circularize at the time of telomere replication (Wellinger et al. submitted). Here we demonstrate that those loci previously shown to acquire single stranded tails are indeed telomeres and that single stranded TG1-3 cannot be observed in non-telomeric C1-3A/TG1-3-tracts. Moreover, we demonstrate that the formation of circular DNA by short linear plasmids is not restricted to plasmids containing a 2 microns origin of replication but can also be detected for plasmids containing ARS1. PMID- 1291237 TI - Replisome pausing in mutagenesis. AB - E. coli cells containing a temperature-sensitive dnaE mutation, in the alpha subunit of holoenzyme DNA polymerase III, do not survive at the restrictive temperature. Such cells may survive in the presence of the pcbA1 mutation, an allele of the gyrB gene. Such survival is dependent on an active DNA polymerase I. Evidence indicates that DNA polymerase I interacts directly in the replisome (REP.A). Despite normal survival for cells using the pcbA replication pathway after some type of DNA damage, we have noted a failure of damage-induced mutagenesis. Here we present evidence supporting a model of replisome pausing in cells dependent upon the pcbA replication pathway. The model argues that the (REP.A) complex pauses longer at the site of the lesion, allowing excision repair to occur completely. In the normal replication pathway (REP.E) bypass of the lesion occurs, fixing the mutation. PMID- 1291238 TI - Initiation of replication in the Chinese hamster dihydrofolate reductase domain. AB - Two-dimensional (2-D) gel analysis of replication intermediates in the Chinese hamster dihydrofolate reductase domain has suggested that nascent chains can initiate at any of a large number of sites scattered throughout a approximately 50 kb "initiation locus" (although the level of initiation detected at any given site within this region was relatively low). This result contrasts markedly with data from an in vitro strand switching assay suggesting that > 80% of initiations occur within a single 500 bp fragment lying within the initiation locus. In an effort to reconcile these two disparate views of the initiation reaction, we have questioned the validity of our 2-D gel data in several ways. We show here that: 1) the number of replication bubbles detected in the DHFR locus in the early S period is markedly increased when the cells are released from a synchronizing agent that inhibits initiation per se, rather than from aphidicolin, which is a chain elongation inhibitor; 2) initiation in the DHFR domain occurs only during the first 90 min of the S period, as would be expected of an early-firing origin; 3) a pulse of 3H-thymidine moves through the structures observed on 2-D gels with the kinetics expected of bonafide replication intermediates; and 4) preparations of replication intermediates that are subsequently analyzed on 2-D gels appear, by electron microscopy, to represent the typical theta structures and single forked molecules expected of bidirectional origins of replication; no unusual structures (e.g., microbubbles) were seen. PMID- 1291239 TI - A human DNA replication origin: localization and transcriptional characterization. AB - A single-copy 13.7 kb human DNA region (L30E) located on Ch. 19 p13.3 contains an origin of DNA replication in myeloid HL-60 cells. The origin was localized, by means of quantitative PCR within approximately 3000 bp, in a highly transcribed region containing at least two closely spaced genes with the same polarity of transcription, one encoding lamin B2 and the other an unidentified protein. The origin region overlaps an undermethylated "CpG island" at the 5'-end of the second transcription unit. A binding site (CACGTG) for basic helix-loop-helix (bHLH) DNA binding proteins such as USF/MLTF or MYC-MAX was located by DNase I footprinting analysis in the promoter of the second gene. DMSO differentiation of HL-60 cells, that completely shuts off replication, also drastically reduces the transcription of L30E region. On the other hand such treatment does not modify the methylation pattern of the CpG island and does not abolish the DNase I protection of the bHLH binding site. PMID- 1291241 TI - Adenovirus DNA replication: the function of the covalently bound terminal protein. AB - Initiation of Adenovirus DNA replication in vitro requires the presence of three viral proteins (pTP, pol, DBP) and two cellular transcription factors, NFI and Oct-1, that stimulate replication more than 100-fold. NFI assists in binding and positioning of the DNA polymerase in the origin whereas Oct-1 changes the structure of origin DNA. Optimal templates contain, in addition to origin sequences, the covalently bound viral terminal protein (TP). This terminal protein stimulates the template activity over 20 fold compared to protein-free templates. To study the way in which TP exerts its function in vitro we devised a novel method to isolate and label a short origin containing fragment in which the TP was bound in a functional form. This fragment replicated very efficiently and could be used for studying the binding of other replication proteins. Employing alpha-chymotrypsin digestion we show that for enhancement of replication in vitro only a small part of TP is required. PMID- 1291240 TI - Structural and functional studies on phi 29 DNA polymerase. AB - The Bacillus subtilis phage phi 29 DNA polymerase, involved in protein-primed viral DNA replication, contains several amino acid consensus sequences common to other eukaryotic-type DNA polymerases. Using site-directed mutagenesis, we have studied the functional significance of a C-terminal conserved region, represented by the Lys-X-Tyr ("K-Y") motif. Single point mutants have been constructed and the corresponding proteins have been overproduced and characterized. Measurements of the activity of the mutant proteins indicated that the invariant Lys and Tyr residues play a critical role in DNA polymerization. Interestingly, substitution of the invariant Lys either by Arg or Thr, produced enzymes with an increased or a largely reduced, respectively, capability to use a protein as primer, an intrinsic property of TP-priming DNA polymerases. On the other hand, the viral protein p6, which stimulates initiation of phi 29 DNA replication by formation of a nucleoprotein complex at both DNA replication origins, increased (about 5-fold) the insertion fidelity of phi 29 DNA polymerase during the formation of the TP dAMP initiation complex. We propose a model in which the special strategy to maintain the integrity of the phi 29 DNA ends, by means of a "sliding-back" mechanism, could also contribute to increase the fidelity of phi 29 DNA replication. PMID- 1291242 TI - Identification and characterization of a complex chromosomal replication origin in Schizosaccharomyces pombe. AB - In the budding yeast, S. cerevisiae, two-dimensional (2D) gel electrophoresis techniques permit mapping of DNA replication origins to short stretches of DNA (+/- 300 bp). In contrast, in mammalian cells and Drosophila, 2D gel techniques do not permit precise origin localization; the results have been interpreted to suggest that replication initiates in broad zones (several kbp or more). However, alternative techniques (replication timing, nascent strand polarity analysis, nascent strand size analysis) suggest that mammalian origins can be mapped to short DNA stretches, just like S. cerevisiae origins. Because the fission yeast, Schizosaccharomyces pombe, resembles higher organisms in several ways to a greater extent than does S. cerevisiae, we thought that S. pombe replication origins might prove to resemble--and thus be helpful models for--animal cell origins. An attempt to test this possibility using 2D gel techniques resulted in identification of a replication origin near the ura4 gene on chromosome III of S. pombe. The 2D gel patterns produced by this S. pombe origin indeed resemble the patterns produced by animal cell origins and show that the S. pombe origin cannot be precisely located. The data suggest an initiation zone of 3-5 kbp. Some aspects of the 2D gel patterns detected at the S. pombe origin cannot be explained by the rationale of initiation in broad zones, suggesting that future biochemical and genetic studies of this complex origin are likely to provide information useful in helping to understand the apparent conflict between the 2D gel mapping techniques and other mapping techniques at animal cell origins. PMID- 1291244 TI - [Hereditary motor and sensory neuropathy]. AB - The report consisted of 10 cases of hereditary motor and sensory neuropathy (HMSN). There were 7 males and 3 females. Their ages ranged from 11 to 42 (average 24.6) years, ages of onset varied from 7 to 34 (average 17.3) years. Hereditary history was showed in 4 cases. The clinical features of all 10 cases had peroneal muscular atrophy, 8 of 10 cases also had involvement of the upper limbs, 7 of 10 cases had pes arcuatus. The conduction velocity was obviously slow in 5 cases and slightly slow in the others. Oion-bulb hypertrophic neuropathy was demonstrated in sural nerve biopsies of 5 cases. Neuronal axonal degeneration were found in the remaining 5 cases. Clinical classification, clinical features and pathological characteristics were discussed. PMID- 1291245 TI - [A study on middle cerebral artery territory infarction with transcranial Doppler sonography]. AB - The transcranial Doppler sonographic findings of 40 patients with middle cerebral artery (MCA) territory infarction were compared with those of 40 controls. The results showed that in the group of acute phase patients there was a large reduction of MCA mean flow velocity (Vm) of the infarcted side compared with the normal hemisphere (P < 0.01) and controls (P < 0.05). At the same time the anterior cerebral artery (ACA) Vm rose on both sides (esp. on the infarcted side) in comparison with controls (P < 0.05). The posterior cerebral artery (PCA) Vm did not change significantly (P > 0.05). In the group of chronic phase patients there were changes similar to the group of acute phase patients in MCA Vm and ACA Vm, but not statistically significant. Follow-up TCD examinations were carried out in 8 cases during the acute phase of stroke. We found that the decreased MCA Vm on the infarcted side returned to normal in 4 cases, remained lower in another 2 cases within 4 weeks after onset. The increased MCA Vm on the infarcted side in 2 cases returned to normal within 2 weeks after onset. Various types of TCD findings in patients with MCA occlusion were described and analysed. PMID- 1291243 TI - Characterization of vaccinia virus DNA replication mutants with lesions in the D5 gene. AB - The vaccinia virus D5 gene encodes a 90 kDa early protein that is essential for viral DNA replication. In this report we map and explore the phenotypes of the temperature sensitive mutants bearing lesions in this gene: ts17, ts24, ts69 (WR strain) and ts6389 (IHD strain). Viral DNA synthesis was virtually undetectable during non-permissive infections performed with ts17, and incorporation of 3H thymidine ceased rapidly when cultures were shifted to the non-permissive temperature in the midst of replication. The D5 protein may therefore be involved in DNA synthesis at the replication fork. The lesions of the four mutants were localized within the D5 orf by marker rescue, and the single nucleotide changes responsible for the ts phenotype of the three WR mutants were identified. Unexpectedly, the three alleles with N-terminal mutations were impaired in marker rescue when homologous recombination with small (< 2 kb), intragenic DNA fragments at 39.5 degrees C was required. This deficiency was not due to degradation of transfected DNA under non-permissive conditions. Efficient marker rescue could be restored by incubation at the permissive temperature for a brief period after transfection, suggesting a requirement for functional D5 in genome/plasmid recombination. Marker rescue under non-permissive conditions could alternatively be restored by co-transfection of unlinked but contiguous DNA sequences. PMID- 1291246 TI - [The diagnostic value of magnetic resonance imaging on neuromuscular diseases]. AB - The article concentrated on the study of skeletal muscles of four extremities in 12 cases of different kinds of neuromuscular diseases and 4 volunteers with MRI. The results revealed: MRI could clearly display individual muscle, muscle groups or abnormal muscles morphologically. It could also demonstrate the difference between the neurogenic and myogenic changes. In patients with progressive muscular dystrophy (PMD), the gracilis m. and sartorius m. were relatively intact. In patients with primary myopathies, the severity of MRI changes was consistent with the severity of the illness and the EMG changes. The results indicated that MRI examination was helpful in the diagnosis of neuromuscular disorders. It can define the distribution and the severity of impaired muscles. In addition, MRI could be used to select the appropriate muscles for EMG examinations or muscle biopsies. Selective muscular impairments might be the characteristics of patients with PMD. PMID- 1291247 TI - [A study of muscle fibers typing on Duchenne muscular dystrophy]. AB - Quantitative analysis of muscle fibers typing in 15 cases of Duchenne muscular dystrophy has been done. Mean diameter, area, variability coefficient were estimated by computer. The results show that type IIC fibers were remarkably increased and type IIB fibers was deficiency in DMD. Atrophy and hypertrophy occurred in different typing fibers. The results indicated that DMD has a prominent atrophy and hypertrophy and active regenerating process. PMID- 1291248 TI - [A clinicopathological study of neuronal ceroid lipofuscinosis]. AB - 4 unrelated patients with infantile type (one case), late infantile type (one case), juvenile type (two case) of neuronal ceroid-lipofuscinosis were reported. The pathological study by brain biopsy was carried out with light and electron microscopes as well as histochemical methods. Ultrastructurally, the infantile type showed deposits of lipofuscin bodies, fingerprint bodies, and the late infantile type showed a lot of curvilinear bodies and paracrystalline bodies. The ultrastructural configuration in the juvenile type is more heterogeneous and consisted of combination of lipofuscin bodies, fingerprint bodies and multilamellar structures. It was emphasized that fingerprint bodies were first discovered in infantile type, which might challenge the view that only lipofuscin bodies can be found in infantile type. PMID- 1291249 TI - [ELISA for detection of anti-filamin antibody in sera from patient with myasthenia gravis]. AB - The activity of anti-filamin antibody was determined in sera from 128 patients with myasthenia gravis (MG) by enzyme-linked immunosorbent assay (ELISA). The positive rate was 77.34%. No correlation was observed between anti-F-ab and nAchRab and CAEab. The antibody-absorbtion test were positive. The result demonstrated that anti-F-ab may play some role in the pathology of MG. The clinical use of ELISA for detection of anti-F-ab may help to diagnose MG. PMID- 1291251 TI - [Preliminary study of changes in plasma prostaglandin E1 in rats with experimental "schizophrenia"]. AB - We referred to Borison's method of making the model schizophrenia. Rats were injected d-amphetamine intraperitoneally once a day so that the schizophrenia models were established within four weeks. After five weeks, rats with schizophrenia were treated with chlorpromazine. Contents of plasma prostaglandin E1(PGE1) in rats were determined before and after treatment respectively. This study demonstrated that contents of plasma PGE1 in rats receiving amphetamine for four weeks were higher than those in control animals (P < 0.05). At this time, male rats' stereotypy scores were 3.5 and female stereotypy scores 5. But contents of plasma PGE1 in rats with schizophrenia approached those in control animals with giving amphetamine once a day continuously. Contents of plasma PGE1 decreased in rats with schizophrenia receiving chlorpromazine. PMID- 1291250 TI - [A case-control study of risk factors on Alzheimer's disease. Multicenter collaborative study in China]. AB - A case control study to assess the possible risk factors associated with Alzheimer's disease (AD) among Chinese population was conducted on 126 clinical diagnosed AD patients and 252 matched by sex, age, nationality non-demand neighborhood as control. Factors significantly associated with AD cases were: family history of dementia in first degree relatives, family history of psychoses in first degree relatives, few interests and heavy negative life events during individual's life time. Neither family history of Down's syndrome, antecedent history of head trauma, nor other condition that might support immune hypotheses were significantly associated with AD cases. The data from this study support the familial/genetic hypotheses of AD and also the role of psychosocial factors in AD. PMID- 1291252 TI - [Distribution of common symptoms in 2500 schizophrenics and their comparative analysis on the background of times and culture]. AB - In the paper, the distribution of the common symptoms in 2,500 Schizophrenics was reported, including 1,600 cases in Shanghai Mental Health Center, 500 cases in Chuan Sha County Mental Hospital, 200 cases in Nan Hui County Mental Hospital in Shanghai and 200 cases in Su County Mental Hospital in An Hui province respectively. In the 2,500 cases, apart from 1,600 cases including 500 cases discharged from 1964 to 1965, and 500 cases discharged from 1984 to 1985 in Shanghai Mental Health Center, the rest was hospitalizing during 1988 to august of 1990. Among these patients, 67 symptoms were shown in which 47 symptoms were much common. There was the most significant difference in the 22 symptoms of the 23 much more common symptoms between 1960 and 1980s (P < 0.01). According to the comparison of the various cultural background, there was the most significant difference in 15 symptoms (P < 0.01). PMID- 1291253 TI - [Predicting the effects of haloperidol on schizophrenics by quantitative pharmaco EEG]. AB - In order to predict the short-term-outcome of schizophrenics under the treatment of haloperidol, changes of 15 schizophrenic subjects' EEG after 4 mg haloperidol oral intake were monitored with the method of QPEEG. The result of discriminate analysis showed that the more similar to typical EEG pattern of neuroleptics the patients showed, the better the patients responded to haloperidol treatment. Meanwhile, the haloperidol therapeutic mechanisms of brain electro-physiology and the electro-physiological characteristics of schizophrenics were also discussed. PMID- 1291254 TI - [A study on effects of parents age, birth order and mental retardation of unknown etiology]. AB - On this report 461 matched cases of mental retardation of unknown aetiology were analysed on the relationship between the diseases and the parents age, birth orders with conditional Logistic regression. These cases were accurately diagnosed and selected from the Epidemiologic Survey of genetic diseases of Sichuan, China. The results found that mental retardation of unknown aetiology is related to the age of parents and birth order. The paternal age is the main factor while the maternal age in not a significant effect and birth order also in not a significant effect after readjusting the other factors. Compared to paternal age group of under 25. There are significant increase of relative risks of age group 30-34 and 45 above, about 1.8 and 2.7 fold increase in univariate analysis and 1.9 and 3.3 fold increase in controlling the maternal age and birth order, a chi-square test for trend of distribution of paternal age also indicates a significant dose response relationship between increasing risk with age. The significance of result and methods of analysis were discussed. PMID- 1291255 TI - [Frequency of sex chromatin among mental patients]. AB - The frequency of sex chromatin of 2000 cases of mental patients are observed in this paper. The frequency of Y chromatin in male and X chromatin in female was 28.01% and 26.86% respectively, whereas only 16.97% and 17.84% respectively in the control group. The mental patient group is higher than the control group significantly (P < 0.0001). It may be influenced by some psychotropic drugs and the factor of course. Positive X chromatin in the male patients was 8 cases and karyotypes of chromosome was XXY type all. The incidence of XXY type is 0.77% and significant higher than the control group (0.18%, P < 0.01). It suggested that ratio of add one X chromosome in the male mental patients be obviously increased. The authors indicated if this examination be routinely used in clinic that would prevent misdiagnosis and would raise accuracy of diagnosis. PMID- 1291257 TI - From the dental chair: An HIV patient's views of his dental treatment. Interview by Rudy Bianco. PMID- 1291256 TI - [Computerized tomography findings and clinical analysis of psychiatric disorder of praecox from head injury. Report of 52 cases]. AB - This article reports and analyses 52 cases of psychiatric disorders of praecox from head injury. These patients included 39 males and 13 females. They were 13 80 years old. All of them examples by CT scan and found intracerebral hematomas or cerebral contusion. The shortest course of disease was 3 day, and the longest course was 53 day. 44 cases (84.7%) appear psychiatric disorders in first week. The most frequent psychiatric symptoms was disturbances of consciousness and dysmnesia. Disturbance of emotion, change of personality were also observed. Frequency of psychiatric disorders was same in brain traumatic of left or right lateralis. Course of disease and degree of psychiatric symptoms had nothing to do with size of hematoma and cerebral contusion, and relate to compression of ventricles of the brain. Encephalo-edema around the focus leading to regional compression of the brain was important factors for the disorder. The appearance of this disorder was early, course of disease was short, and prognosis was good. PMID- 1291258 TI - Dental school provisions for HIV-positive patients: should students have a choice? PMID- 1291259 TI - Management of patients undergoing radiation therapy of the head and neck. PMID- 1291260 TI - Prevention, practice, and the year 2000. PMID- 1291261 TI - Should it be mandatory for all health professionals to provide documentation concerning their HIV status? PMID- 1291262 TI - Facts about AIDS. PMID- 1291263 TI - HIV-related gingival and periodontal disorders. PMID- 1291264 TI - Get a hold on your insurance patients: your insurance game strategy. PMID- 1291265 TI - Imaging in clinical dentistry. PMID- 1291266 TI - Finding a practice location. PMID- 1291267 TI - On associateships and entering partnerships. PMID- 1291268 TI - Smart marketing. PMID- 1291269 TI - The American Dental Association: meeting your personal and professional needs. PMID- 1291270 TI - Keep that shark (lawyer) from making you his main course. PMID- 1291271 TI - Making computer selection an easy dental process. PMID- 1291272 TI - Quality staff: how to get'em and keep'em. PMID- 1291273 TI - Floor of mouth swelling: case report. PMID- 1291275 TI - Success in dentistry. PMID- 1291274 TI - Chitosan: the hemostatic agent. PMID- 1291276 TI - Infection control and the handpiece. PMID- 1291277 TI - Management by design. PMID- 1291278 TI - Ethics. Dilemmas in dentistry. PMID- 1291279 TI - Getting your point across. Communication wins over patients. PMID- 1291280 TI - The facts about gingival hyperplasia. PMID- 1291281 TI - Developing team leaders. PMID- 1291282 TI - 10 barriers to quality staff meetings. Don't let any excuses get in the way of success. PMID- 1291283 TI - Dealing with dental phobias. Behavioral techniques that turn fears into friendship. PMID- 1291284 TI - Defeating chemical dependencies. Utah school provides stage for ideas, emotions. PMID- 1291285 TI - Feeling good affects your work. A team approach to health and productivity. PMID- 1291286 TI - When latex gloves aren't a perfect fit. Reactions, sensitivity plague 12 percent of HCWs. PMID- 1291287 TI - [Immunotherapy of human retinoblastoma with RGNTF-monoclonal antibody using nude mice as model]. AB - Retinoblastoma in nude mice as an animal model was developed by injecting cultured human retinoblastoma cell line(Rb) Y79 into the anterior chamber of eyeball. It was treated by direct injection of RGNTF-McAb into the Rb tumor. Ten out of 30 eyeballs with Rb inoculation did not develop tumor (32% inhibition) if Rb cell suspension was mixed with the RGNTF-McAb before injection; whereas in the control, all 40 but 3 eyeballs developed tumor (7%) when Rb cell suspension alone had been injected. This 32% of inhibition of Rb tumor formation by RGNTF-McAb was very significant (T > 2.58, P < 0.01). The results of immunotherapy of 46 eyeballs with Rb tumor developed 10 days after inoculation by RGNTF-McAb for 2 months revealed that the proportion of grade III-IV tumors before and after therapy reduced from 53% to 26% and that of grade I-II tumors increased from 47% to 74%. Feulgen DNA staining of tumor sections after therapy revealed that the average DNA contents in Rb cells decreased significantly (P < 0.01) from 16.2 +/- 2.6 in grade III-IV to 5.3 +/- 1.2 in grade I-II compared to that of the untreated control 18.8 +/- 3.2. Numerous white cells infiltrating the Rb tumor, hyperplasia of fibrous tissues, and no spreading and metastasis of the tumor tissue were observed in the treated eyeballs; whereas Rb tumor was spreading to the optic nerve and superior colliculus in the untreated eyeballs. Therefore, the RGNTF-McAb can not only inhibit the growth of Rb cells but also limit their spreading and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291288 TI - [Biological characteristics of tumor growth delay in human nasopharyngeal carcinoma xenograft (NPC-837) after irradiation]. AB - Tumor growth and cell cycle of human nasopharyngeal carcinoma xenograft in nude mice (NPC-837) after irradiation were studied. After cobalt-60 irradiation of 5.0Gy, 7.5Gy, 10Gy, 15Gy and 20Gy, the tumor volume was reduced to 80, 70, 50, 35 and 10 percent of the control, respectively. However, the tumors began to grow again. The time (in days) the tumors took to reach the volume of the control was radiation dose-dependent. With 20 Gy irradiation the tumor volume was kept at 10% of the control level for as long as 20 days before regrowth occurred, but it never reached the control level up to 108 days of observation. A mean G2 cell block rate of 1.21% after irradiation was observed and a G2 cell block was marked after 7.5Gy irradiation. The results indicate that NPC-837 is a very radiosensitive and valuable model for the radiobiological research of solid tumors. PMID- 1291289 TI - [Effects of Se-enriched malt cakes on UV benzo(a)pyrene induced unscheduled DNA synthesis of lymphocytes from high risk population of lung cancer]. AB - Se-malt cakes containing 300 micrograms selenium were given daily to men from high risk area of lung cancer and the influence of ultraviolet light (UV) and be benzo(a)pyrene (B(a)P) induced unscheduled DNA synthesis (UDS) of peripheral lymphocytes were determined. After Se-supplementation for 6 months, the Se levels in serum, hairs and activity of GSH-px were increased by 89%, 67% and 178%, respectively. The ratio of UV-induced UDS was decreased from the mean value of 2.47 in the control to 1.61 (P < 0.05) in the Se-group. After Se-intake for one year, the Se levels were elevated by 78% in serum, 83% in hairs and 56% in GSH-px activity, while the mean value of B alpha P-induced UDS was reduced from 2.21 in the control to 1.47 (P < 0.05) in the Se-group. The results of the present study indicate a blocking effect of Se-supplementation to UV- and B alpha P-induced UDS of peripheral lymphocytes from high risk subjects for lung cancer. PMID- 1291290 TI - [Stable and efficient expression of human interleukin-6 cDNA in mammalian cells after gene transfer]. AB - Following reverse transcription and PCR amplification, the human interleukin-6 (IL-6) cDNA was cloned from total RNA of activated human tonsillar mononuclear cells. Southern blot showed the presence of specific band, and its DNA sequence demonstrated that the fragment was 650 bp in length, spanning the complete coding region and part of 5' and 3'-untranslated regions. The human IL-6 sequence seemed to be well conserved. One nucleotide change at 429 position was observed, but this change did not affect the amino acid composition. After inserting the cloned cDNA into retroviral vector XM-6, the recombinant was packaged in PA317 cells and the amphotropic virus titer reached 5 x 10(5) CFU/ml. Human IL-6 was expressed in mammalian cell line SP2/0 cells, after being infected by the constructed retrovirus. The G418 resistant SP2/0 cells secreted IL-6. Its supernatant was able to maintain in vitro growth of the IL-6 dependent T1165 cell line. Northern blot analysis of the transfected SP2/0 cells showed significantly elevated IL-6 message, being consistent with the result of T 1165 bioassay. The expression was stable during the 12 month period of observation. The hybridoma cells, formed after fusion of the transfected SP2/0 cells and lymphocytes, exhibited accelerated growth. PMID- 1291291 TI - [Diagnostic significance of multinuclear giant cells in lymph node fine needle aspiration]. AB - Enlarged lymph nodes, commonly seen in inflammatory or tumorous conditions, is often suspected as Hodgkin's disease in cytologic diagnosis. Twenty cases originally diagnosed as Hodgkin's disease by fine needle aspiration of lymph nodes are reported. Eighteen of these 20 cases were checked by histopathology. It was found that only 3 had reached the correct diagnosis. The authors believe that by thorough understanding of the origin and characteristics of various types of multinuclear giant cells, differentiation from Hodgkin's disease is possible. PMID- 1291292 TI - [Comparative pathologic study on the peri-ulcer mucosal lesion around benign and malignant gastric ulcer]. AB - 3441 peri-ulcerous mucosal lesions around benign and malignant gastric ulcers (1479 benign gastric ulcers, 421 cancerous degeneration of benign ulcers and 1541 ulcerative carcinomas) were studied comparatively. It was found that the ulcer of cancerous degeneration of benign ulcer was small and the epithelial regeneration at the ulcer's edge and fusion of the muscularis mucosa with the muscularis propria were very common. The cancerous tissue, extending down to the submucosa, was found at the margin but not at the base of the ulcer. Lymph node metastasis was rare. Therefore, the cancerous degeneration of ulcer was most likely an early carcinoma. These findings conform well with Hauser's criteria. Chronic atrophic gastritis intestinal metaplasia (IIb and type II), moderate and severe dysplasia were more commonly observed in cancerous degeneration of ulcers than in benign peptic ulcers or ulcerative carcinoma. These results suggest that multiple biopsies should be taken from the edge of chronic ulcers. PMID- 1291293 TI - [Intra-arterial digital subtraction angiography (IADSA) in liver metastases]. AB - From Dec. 1988 to Dec. 1990, fifty cases of metastatic liver tumors were examined with IADSA. The present article analysed the DSA imaging in this series and divided the DSA appearances of the tumor vessels into five types: 1. Dilatation and enlargement, 29 cases (58%); 2. Stricture and narrowing, 17 cases (34%); 3. Zigzag and tangle, 39 cases (78%); 4. Intermittence and discontinuance, 20 cases (40%); 5. Removement and encirclement, 34 cases (68%). Sometimes several types could be found in one case. There were two cases in this group without any tumor vessels. The DSA appearances of tumor stains were also divided into four types: 1. Circular, cystiform and honeycomb-like, 9 cases (18%). 2. Nodular masses, 13 cases (26%). 3. Spots and flakes, 8 cases (16%). 4. Wadding-like, 15 cases (30%). There were 5 cases without any tumor stains. In no case there was AVM or cancerous embolus in portal vein. In this series, hypervascular lesions were observed in 17 cases (34%), midvascular lesions in 25 cases (50%), and hypovascular lesions in 8 cases (16%). PMID- 1291294 TI - [Shortcomings of esophagogastric stapling device and their correction and prevention]. AB - From 1985 to 1991, 202 patient with cancer of the esophagus or gastric cardia were resected with esophagogastric stapling device. The shortcomings were: 1. Necessity of second stapling-5 cases, and 2. Defective performance-9.1% (19/207 times) which was due to; a. failed coupling (7 times), b. incomplete resection (6 times), c. tearing of the muscular layer (4 times), d. gastric tube stapled into the stoma (1 time), and e. fall-off of thread from the purse-string suture at the esophageal stump (1 time). The correction procedures were: 1. Repair by hand suture (6 times), 2. Repeated stapling (5 times), 3. Repair of muscle tear by silk sutures (6 times), and 4. Second resection (2 times). Prevention of these shortcomings are discussed. The authors believe the stapling device can not replace manual suturing. PMID- 1291296 TI - [Surgical treatment of esophageal cancer in post-subtotal gastrectomy patients]. AB - Among the 1285 cases of esophageal cancer operated in our hospital during the interval 1985-1990, 11 had had subtotal gastrectomy earlier, with an incidence of 0.86%. Among these 11 cases, two had upper thoracic segment lesions which were resected and reconstructed by transverse and descending colon transplantation into the neck. Right postero-lateral thoracotomy, upper abdominal and left neck incisions were used. Nine patients had esophageal cancer in the middle and lower thoracic segment and 7 of them were operated by transplanting the remaining stomach with spleen and caudal portion of pancreas into the left thorax and esophago-gastrectomy with the remaining stomach. Exploratory thoracotomy only was done in the other 2 patients. No complication occurred. Billroth type II gastrectomy was found to be easier than Billroth type I to move the remaining stomach together with the spleen and pancreas up into the thorax and to anastomose supra-aortically. There was no direct cause-effect evidence between gastrectomy and the site of esophageal cancer. The purpose for gastrectomy (ulcer or cancer) and the type of gastrectomy (Billroth type I or II) were irrelevant to the subsequent development of esophageal cancer. PMID- 1291295 TI - [Reconstruction of trachea, carina and bronchus for tumors of the trachea, carina and lung]. AB - This paper reports on 70 patients with tumors of the trachea, bronchus and lung treated by reconstruction of the trachea, carina and the main bronchus (21 cases) and sleeve lobectomy (49 cases). Postoperatively, 2 patients died of tracheo innominate artery fistula and 2 developed empyema which was healed. There was no mortality in the sleeve lobectomy patients. The 3- and 5-year survival rates of the cancer patients treated by reconstruction of trachea, carina and main bronchus were 54.5%(6/11) and 33.3%(3/9), respectively. The 3- and 5-year survival rates of lung cancer patients treated by sleeve lobectomy were 46.6% (14/30) and 33.3% (7/21), respectively. PMID- 1291297 TI - [Combination of radiotherapy and surgery for advanced cancer of the vulva]. AB - From 1970-1985, seventy-six patients with advanced carcinoma of the vulva were treated. It accounted for 58.9% of all vulvar cancers seen in the same interval. According to the revised FIGO Staging System of Vulvar Cancer, 64 had Stage III, and 12 had Stage IV lesions. Fourty-eight patients had tumor extending to the distal urethra, vagina or anus. Fifty-one were treated by radiotherapy combined with radical vulvectomy and inguinal lymphadenectomy, 10 by surgery alone, 9 by radiotherapy alone and 6 by palliative radiotherapy. In 20 (55.6%) patients the tumor was reduced > or = 50% and in 4 (20%) patients the tumor completely disappeared after pre-operative radiation as shown in pathologic examination of the resected specimens. The 5-year survival rate was 46.9% for Stage III, 33.3% for Stage IV disease, with an over-all 5-year survival of 60.8% on the combined group. Surgery alone gave a 5-year survival rate of 30%. All the patients died of cancer within 5 years in the radiotherapy and palliative radiation groups. It is suggested that combined radiotherapy and surgery be preferred for advanced cancer of the vulva. Technique of encompassing the vulvar and inguinal areas needs to further studied and improved. PMID- 1291298 TI - [Photodynamic therapy in the treatment of carcinoma of the urinary bladder and prevention of its recurrence]. AB - Sixty-eight patients with carcinoma of the urinary bladder were treated with photodynamic therapy (PDT). The results demonstrated that the tumors of 1-2 cm in diameter had best results, the tumors of 2-4 cm in diameter should be irradiated repeatedly or with intensified energy density, whereas those above 4 cm in diameter or those that had infiltrated deep muscular layer or neck of the bladder showed poor results. In this group, the total effective rate is 91%, the 5 year cure rate is 71.1%, and the 5 year recurrence rate is only 27.9%. In addition, we used preventive photodynamic irradiation of total bladder in 14 cases with bladder carcinoma who had undergone treatment. The 2 year recurrence rate was 7.1% (1 case), demonstrating a very promising result. The mechanism of tumor destruction with PDT action, the reasons for low recurrence rate, the advantages and disadvantages of this therapy were also discussed. PMID- 1291299 TI - [Carcinoid tumors of the thymus--a report of 7 cases]. AB - Carcinoid tumor of the thymus is rare and often clinically misdiagnosed as thymoma. However, those two types of tumors differ from each other greatly in their origin, biological behavior, accompanying syndromes, pathological features as well as prognosis. Seven cases of this tumor are presented here, which have had surgical intervention and pathological confirmation. Two of them were accompanied with Cushing's syndrome, another one was associated with pericarditis. Resection was accomplished in 5 cases and exploratory thoracotomy in 2 cases. Among the 7 cases, the two cases receiving exploratory thoracotomy died of tumor in its late stage. One patient died of widespread bone metastases 2 years after resection. One had tumor recurrence 3 years after original tumor resection and received another surgical operation. The characteristic features of carcinoid tumors of the thymus are diagnostic difficulty, potential malignancy, frequent recurrence and extrathoracic metastasis for prolonged period postoperatively. Histopathological, electron microscopic and immunohistochemistry examinations may be required in making an accurate pathological diagnosis. Thorough surgical excision of the primary and secondary tumors is of great importance in treatment. PMID- 1291300 TI - [Advanced prostate cancer--an analysis of 17 cases]. AB - Prostate cancer is a disease mostly effecting aged men. The incidence rate of this disease is much lower in China than in Europe and America. However, certain data have been accumulated indicating an increasing tendency in this country in recent years. The present report also supports this view and suggest the importance of strengthening of epidemiological research in this area in future. The problem how to treat patients with advanced prostate cancer is of essential importance since most cases are diagnosed in III or IV stage of the disease. In the present study, 10 out of 26 suspected cases (38.5%) was diagnosed by needle aspiration biopsy, being 90.9% of 11 cases confirmed histopathologically. The elevation of tumor maker acid phosphatase activity was positive in 8 out of 17 cases (47.1%). In this group, 11/17 (64.7%) received bilateral orchidectomy plus estrogenic hormones. The effective rate was 81.9% (9/11). Relapse occurred in 4 out of the 9 cases (44.4%), probably due to estrogenic hormone-dependence. PMID- 1291302 TI - Digital subtraction radiography for assessment of simulated root resorption cavities. Performance of conventional and reverse contrast modes. AB - A previous study of the sensitivity and accuracy of a standardized radiographic technique for the disclosure of root cavities in a cadaver material indicated that it was not possible to perceive small artificial "resorption" cavities. Using the same material, the aim of the present study was to evaluate whether the use of subtraction radiography would improve the detection of root cavities. In an autopsy material of five mandibular blocks each containing two premolars, small, medium, and large cavities were drilled in the cervical, middle, and apical thirds of the proximal and oral root surfaces. Each jaw block was radiographed before (B) and after (A) cavity preparation with three different exposure times resulting in light, medium, and dark film densities. The radiographs were digitized. Digital subtraction was performed between the A- and B images of varying densities by a computer program developed for dental subtraction radiography. Conventional and reverse contrast modes of the subtraction image were assessed independently by four observers. The results showed small inter- and intraobserver differences in diagnostic accuracy for assessment of total number of root cavities. Original film density did not influence the diagnostic performance in the resulting subtraction image. Contrast mode in the subtraction image influenced diagnostic performance as the majority of observers did best with the reverse contrast mode (p < 0.05). Some of the small root cavities were disclosed by the subtraction technique, but overall accuracy was not increased compared to conventional radiography. PMID- 1291301 TI - Dental materials for posterior restorations. AB - Assessment of the quality of dental restorations by the Ryge system is described. Generally, the quality of dental restorations is shown to be dependent on the technique sensitivity of the restorative material as well as the skill and experience of the dentist. Concerning biocompatibility, adverse reactions related to amalgam restorations are unlikely or scarce, due to small amounts of released mercury. Resin based restorative materials contain a large number of organic compounds and, as such, the toxic and allergenic potentials are unknown. Gold and ceramics turn out to be the most biotolerable dental materials. Based on studies on longevity, data indicate that the median age of amalgam restorations is 10-12 years, of gold castings 13-14 years and more, and of composite restorations 4 years. Data on longevity of ceramic restorations are sparse. Secondary caries appears to be the most frequent cause for replacement of the different restorations, followed by marginal degradation. Secondary caries account for more failures among the resin based restorations than among amalgam. Reviewing the literature, it appears that amalgam is the best and most economic dental material for routine posterior restorations with reasonable durability. Gold is recommended for complex restorations. Resin based composites may be limited to small restorations where cosmetics is the main aspect, as wear and recurrent caries are main problems. Ceramic restorations comprise aesthetic restorations with excellent biocompatibility, however, data on longevity and marginal adaptation are not encouraging. PMID- 1291303 TI - Exposure of dental personnel to chloroform in root-filling procedures. AB - The exposure of dental personnel to chloroform in root-filling procedures was evaluated. Four different root filling procedures were studied. In all the procedures studied, guttapercha was used as the root-filling material and chloroform or sealers containing chloroform were used. Ten teeth in each group were root-filled. In the first group, chloroform and 5% rosin in chloroform were administered in medical cups, in the second group chloroform and Kloroperka NO was administered in medical cups. In Group three a specially designed glass tube (S-endodip) was used for administration and in the fourth group specially selected plastic tubes were used. In the last two groups the sealers were chloroform and 5% rosin in chloroform. When medical cups were used the exposure reached levels close to the accepted limit values in Sweden, indicating that only one root filling per day can be performed without the dental team being unacceptably exposed. Using either the glass tube or the specially designed plastic tube, the exposure was significantly reduced for the dentist (p < 0.005) and for the nurse (p < 0.005). The mean exposure was 19.1 mg/m3 for the dentist and 11.6 mg/m3 for the nurse in the first experimental group. The mean values in the second group were 15.4 mg/m3 and 16.6 mg/m3 respectively. In the third group, the dentist was exposed to a mean of 4.4 mg/m3 and the nurse to 6.3 mg/m3. In the fourth group, the mean exposure was 2.2 mg/m3 and 3.4 mg/m3 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291304 TI - Lay and professional knowledge of methods for emergency management of avulsed teeth. AB - Proper treatment during the first 30 minutes offers the best prognosis for traumatically avulsed teeth. This study sought to determine both lay people's and dental professionals' knowledge of and attitude to emergency procedures. A 12 question survey was administered to 5 groups: (a) parents of learner swimmers and (b) coaches of college sports teams (lay); (c) State Dental Nurses, (d) dentists and (e) dental nurse/receptionists (professional). Respondents totalled 184 (a 32, b 86, c 24, d 18, e 24) i.e. 118 lay and 66 professional. Data revealed that group b had the greatest personal experience of avulsed teeth and groups c and e the least. Public hospital accident and emergency services (A & E) were perceived by all groups as most available. 18% of lay groups could not cite an emergency service. Lay people thought first of A & E for management whereas profession groups preferred the victim's own dentist. Most professional people would replant avulsed permanent teeth and about 1/3 would replant deciduous teeth: 1/2 lay people would replant permanent teeth and 1/8 deciduous teeth. Where treatment was not straightforward lay people would seek advice before acting. Half of the lay groups would transport an avulsed tooth dry. All the professionals had had advice on management of avulsed teeth but only 1/4 of the lay groups. This study highlighted the need for educational campaigns aimed at members of the lay public likely to be involved in the emergency management of traumatically avulsed teeth. PMID- 1291305 TI - Comparative immunohistochemical identification and relative distribution of immunocompetent cells in sections of frozen or formalin-fixed tissue from human periapical inflammatory lesions. AB - The presence of immunocompetent cells (B, Th/i and Ts/c cells and macrophages) and the ratios of these cell populations in periapical lesions (radicular granulomas, radicular cysts and apical scars) were demonstrated immunohistochemically using paraffin and cryo-sections. Thirty-four human periapical lesions were examined for the presence of immunocompetent cells by monoclonal antibodies and the biotin-avidin-horseradish peroxidase method. The T/B cell ratio of radicular cysts was significantly higher than that of both radicular granulomas and apical scars, and the average number of Th/i cells was greater than that of Ts/c cells in the radicular granulomas. However, no significant difference was found between radicular cyst and apical scar. The number of macrophages in radicular granulomas was significantly higher than that of the other lesions. These findings suggested that periapical lesions develop as a result of both humoral and cell-mediated immunological response and indicated that the ratios of immunocompetent cells are different in the different types of periapical lesion. PMID- 1291306 TI - Traumatic bone cyst: case report. AB - The traumatic bone cyst is a lesion whose aetiology and pathogenesis have not been conclusively established. There are several theories and names for this lesion and various forms of management have been reported in the literature. This report outlines the clinical and radiographic findings associated with a case of a traumatic bone cyst. Laboratory investigations were also carried out and their findings are reported. This case was treated jointly by the endodontic and oral surgery departments of an institution and demonstrates the need for close follow up from both departments. In particular, the endodontic aspects of monitoring the pulp status of teeth in the region of such a bone lesion are emphasised. PMID- 1291307 TI - Emergency dental management of a patient with von Willebrand's disease. AB - A patient with von Willebrand's disease presenting for dental treatment requires thorough evaluation prior to the determination of a proper course of treatment. In this case report, a patient with von Willebrand's disease presented to the emergency room with dental trauma. A modified treatment plan, taking into account the severity of the patient's systemic illness and the need for medical management, yielded successful results. PMID- 1291308 TI - An international multicenter study of blood culture practices. The International Collaborative Blood Culture Study Group. AB - An international study was organized to review blood culture practices in 67 medical centers, most of which were teaching hospitals with a total of over 58,000 active hospital beds. The number of blood cultures per admission was generally greater than 0.5 in the USA and less than 0.5 in other countries. Criteria varied for defining a septic episode, as well as for ascribing clinical importance to isolates of coagulase-negative staphylococci; however, septicemia rates tended to be lower in centers in which clinical evaluation was included among these criteria. Staphylococci were ranked first or second among etiologic agents of septicemia in the USA, whereas Escherichia coli was most frequently ranked first among European and Asian centers. All USA centers recommended collection of two blood cultures per septic episode and all but one recommended a maximum number of blood cultures per septic episode, whereas similar recommendations were less common in Europe and Asia. Collection of more than 10 ml per blood culture was more common in the USA than in Europe or Asia. A variety of broth-based systems were used, often in combination with lysis-centrifugation for special (fungal, mycobacterial) or, on occasion, routine purposes. PMID- 1291309 TI - Clindamycin versus phenoxymethylpenicillin in the treatment of acute orofacial infections. AB - The efficacy of clindamycin and phenoxymethylpenicillin in the treatment of orofacial infections was compared in a randomised study in 60 patients: 30 patients received clindamycin 150 mg every 6 h for seven days, and 30 received phenoxymethylpenicillin 1 g every 12 h for seven days. Where indicated incision and drainage were carried out. All patients but one in each group responded satisfactorily to treatment. Although the clindamycin group had a shorter duration of pain, swelling and fever and more favourable laboratory findings, the differences between the groups were not statistically significant. Of the 60 microbiological specimens 23 yielded only anaerobic bacteria, 34 both anaerobic and aerobic bacteria, two aerobic bacteria only and one no growth. In the penicillin group one case of severe diarrhoea occurred, and six patients in the clindamycin group had moderate to severe gastrointestinal discomfort, including one case of Clostridium difficile associated diarrhoea. This difference was however not statistically significant. The results support the continued use of penicillin for treatment of orofacial infections, with clindamycin serving as an effective alternative. PMID- 1291310 TI - Virulence properties of erysipelas-associated group A streptococci. AB - Group A streptococcal isolates (n = 53) recovered from 38 erysipelas patients in 1988 and 1990 in Sweden were analysed with respect to serotype, erythrogenic toxin production and polymorphism in the emm gene region. Serotype determination showed a dominance of type T1M1 (28.6% of the strains), but T type 8 was also prevalent (14.3%). In the majority of the strains only a low production of erythrogenic toxin A was demonstrated, while both toxin B and C production were high. Polymorphism was detected in the emm gene region of T1M1 strains at a frequency of 64%. These erysipelas associated group A streptococci were more heterogenic with respect to serotype distribution and polymorphism in the emm gene region compared to previously studied group A streptococci isolated during an outbreak of serious streptococcal infections in Sweden in 1988/1989. The material included isolates from two cases of recurrence, and typing of the isolates indicated that the patients had been infected by the same serotype as in the primary infection. PMID- 1291311 TI - Underestimation of the incidence of measles in a population of French children. AB - Data on titres of specific antibodies against measles virus and information given by families and physicians were analysed in 133 vaccinated and 117 unvaccinated children. Only 2 of the 133 vaccinated children reported a history of measles, while 131 had detectable levels of antibodies. Measles antibodies were detected in 102 (87.2%) of the unvaccinated children, but a history of measles diagnosed clinically by a physician was reported in only 42 of them. These findings suggest that subclinical cases of measles are possible and contribute to the high circulation of the measles virus in the child population in France. PMID- 1291312 TI - Fatal necrotizing esophagitis due to Penicillium chrysogenum in a patient with acquired immunodeficiency syndrome. AB - Although blue-green molds of the genus Penicillium are ubiquitous in the human environment, invasive penicilliosis is uncommon and primarily encountered among immunosuppressed patients. A patient with HIV infection who died of severe necrotizing esophagitis caused by Penicillium chrysogenum is reported and the relevant English language literature on human penicilliosis is reviewed. Although infectious esophagitis is commonly associated with AIDS, Penicillium esophagitis has not been described in such patients. PMID- 1291313 TI - Three cases of infection with Fusarium species in neutropenic patients. AB - Three cases are reported of disseminated infection due to Fusarium species in severely neutropenic patients. The clinical findings in all patients included fever, painful disseminated nodular skin lesions and severe myalgia. The outcome was fatal despite early administration of amphotericin B. The portal of entry of the organism was probably the nasal sinus in two cases. PMID- 1291314 TI - Emergence of resistance to erythromycin and fluoroquinolones in thermotolerant Campylobacter strains isolated from feces 1987-1991. AB - During the period 1987 to 1991 a retrospective study was performed to determine the resistance of thermotolerant Campylobacter species isolated from feces to erythromycin and fluoroquinolones. Of the 672 strains studied, 614 (91.3%) were identified as Campylobacter jejuni and 58 (8.7%) as Campylobacter coli. During the study period the rate of resistance of Campylobacter jejuni to erythromycin remained relatively stable (0.9-3.5%), while resistance of Campylobacter coli to erythromycin emerged later (1989) with much higher rates (14.8-33%). Overall, 11.8% and 10.7% of Campylobacter jejuni strains isolated after 1987 were resistant to nalidixic acid and ciprofloxacin respectively, resistance increasing from 2.3% in 1988 to 32% in 1991. In 1991 the first strains of Campylobacter coli with resistance to these fluoroquinolones were detected (rates 29% and 26% respectively). Of the strains resistant to nalidixic acid, only 10.9% were susceptible to ciprofloxacin. PMID- 1291315 TI - In vitro antibacterial activity of antiseptics against vaginal lactobacilli. AB - The results of investigations carried out to evaluate the inhibitory activity in vitro of seven vaginal antiseptic douche solutions against several strains of vaginal lactobacilli isolated from asymptomatic women are reported. Some of the products examined showed marked antibacterial activity even at high dilutions and for short exposure times. The post-antibiotic effect of two of these antiseptics on vaginal lactobacilli was also evaluated. The results of these investigations suggest that uncontrolled use of antiseptic products could cause changes in the normal vaginal flora. PMID- 1291316 TI - Comparison of the E test and a reference agar dilution method for susceptibility testing of anaerobic bacteria. AB - The susceptibility of 146 recent clinical isolates of gram-negative and gram positive anaerobes was determined by the E test (AB Biodisk) on both Wilkins Chalgren and PDM ASM II (AB Biodisk) agar. Results of the E test were compared with results obtained by the NCCLS agar dilution method using Wilkins-Chalgren agar. Incubation was for 20 hours and 44 hours in the E test and for 44 hours in the NCCLS method. In general, 44 hour results were more reliable; however, NCCLS readings were made only once after 44 hours. After two days of incubation, 91% of E test results on Wilkins-Chalgren agar were within one dilution and 98% within two dilutions of the corresponding NCCLS values; on PDM agar these values were 89% and 98%, respectively. Major and very major discrepancies combined were less than 1%. PMID- 1291317 TI - Comparative evaluation of the MB-Check system for recovery of mycobacteria from clinical specimens. AB - The performance of the MB-Check system (Roche) in the recovery of mycobacteria from clinical specimens was compared with that of the Bactec radiometric system and conventional culture on Lowenstein-Jensen medium. A total of 1,582 clinical specimens were used for the study; 74 yielded mycobacteria. Organisms of the Mycobacterium tuberculosis and Mycobacterium avium complexes accounted for the majority of isolates. The rate of recovery of all mycobacteria with the Bactec system was 91.9%, with the MB-Check system 79.7% and on Lowenstein-Jensen medium only 54.1%. Combination of the Bactec and MB-Check systems allowed recovery of 100% of isolates. The Bactec system showed a faster detection time than the other two methods. PMID- 1291318 TI - Application of the polymerase chain reaction in the diagnosis of pulmonary toxoplasmosis in immunocompromised patients. AB - Bronchoalveolar lavage (BAL) fluid from 47 immunocompromised patients (26 with AIDS and 21 patients on immunosuppressive therapy) was analysed for the presence of Toxoplasma gondii DNA by means of the polymerase chain reaction (PCR). Specific target DNA derived from the B1 and P30 gene of Toxoplasma gondii was detected in BAL fluids from three patients with AIDS (6.4%). Pneumonia as the presenting feature of disseminated toxoplasmosis was confirmed by both clinical findings and by detection of Toxoplasma gondii DNA in blood obtained from two patients. The findings indicate that PCR has potential value in the detection of Toxoplasma gondii as an etiologic agent of atypical pneumonia in immunocompromised patients. PMID- 1291319 TI - Influence on survival of p24 antigen levels in patients with AIDS or advanced AIDS related complex treated with zidovudine. AB - In a prospective study sixty-eight patients consecutively diagnosed as having AIDS or advanced ARC who were started on zidovudine therapy were followed up for a median period of 725 days. In the 20 patients who had a baseline p24 antigen level above 20 pg/ml, there was a statistically significant trend towards reduction of the p24 antigen levels after the first month of treatment. The median time of survival of the 68 patients was 702 days and the median symptom free period was 510 days. Treatment with zidovudine significantly reduced the p24 antigen levels. However, the life expectancy and the symptom-free period were not statistically different in the patients with p24 antigen levels always below or with levels always above two arbitrarily chosen cut-off points of 20 pg/ml and 50 pg/ml, respectively. PMID- 1291321 TI - Evaluation of culture techniques for diagnosis of catheter-related sepsis in critically ill patients. PMID- 1291320 TI - Activity of meropenem against imipenem-resistant bacteria and selection in vitro of carbapenem-resistant Enterobacteriaceae. AB - The activity of meropenem against 106 imipenem-resistant (MIC > or = 8 mg/l) clinical isolates, and the frequency of resistance to meropenem and imipenem among 24 Enterobacteriaceae was determined. Both agents selected colonies on agar but 20-80% were susceptible after one subculture and 72% of the mutants reverted to susceptibility 1 to 6 months after selection. All isolates and stable mutants were inhibited by > 1 mg/l meropenem, although the MIC of imipenem was 4-16 mg/l. Three of six Xanthomonas maltophilia isolates were susceptible to meropenem (MICs 2-4 mg/l). Pseudomonas aeruginosa lacking outer membrane protein D2 were resistant to meropenem, although isolates with substantially reduced expression of this protein were susceptible. None of the imipenem-resistant gram-positive bacteria were susceptible to meropenem. There was no clear correlation between altered outer membrane protein expression and decreased susceptibility to carbapenems, and there was no apparent involvement of plasmid or chromosomal beta lactamase. PMID- 1291322 TI - Susceptibility to various antimicrobial agents of Staphylococcus aureus isolates from cystic fibrosis patients. PMID- 1291323 TI - [Incidence of tongue diseases based on epidemiologic studies (review of the literature)]. AB - According to the literary data the prevalence of fissured tongue varies between 0.8-60.0%, that of geographic tongue between 0.1-14.3%, that of atrophy tongue between 1.3-9.0% and that of the central papillary atrophy of the tongue between 0.0-3.35%. The wide-ranging diversity concerning the epidemiological data of tongue diseases can be explained by the multiple character of sampling, diagnosis and other methods used in different types of examinations. Disregarding the extremities and considering the average prevalence data, these agree in general with the epidemiological data found in Hungary in 1990: fissured tongue 8.8% geographic tongue 3.0%, atrophic tongue 6.37% and central atrophy of the tongue 0.35% prevalence. PMID- 1291324 TI - [Laser in contemporary dentistry]. AB - In the 30 years of laser history the oral cavity application has always played an important role. In the laboratory diagnostics the analysis of the saliva, tissues and hard dental tissues is performed by laser. In the clinical diagnostics the laser is used for examining the caries, dental matter, in orthodontics, in the surgical analysis of splanchnocranium and the teeth. The photodynamic treatment involves the diagnostic and therapeutic use of the lasers in the management of oral cavity cancers. The soft laser therapy is widely applied in diseases of the oral mucosa, parodontal and pain syndromes, temporomandibular articular diseases, dental inflammations, salivary gland diseases and in osseal healing processes. The surgical lasers are applied in the treatment of teeth, in preprosthetic surgery, salivary gland diseases, precancerous conditions, tumour surgery and in the surgery of hemophilic patients, respectively. In the 90s one cannot speak about modern oral surgery or dentistry without the application of lasers. Though in various fields the research is merely in initial phase (holography, caries treatment, photodynamic therapy, etc.), the lasers are becoming an indispensable (treatment of precancerous conditions, hemophilic patients, diseases of the oral mucosa, etc.). The oral surgical use of lasers might bring about fundamental changes in diagnosis and treatment, becoming a new professional branch, opening up new vistas, representing "future" today. The invention of lasers in 1960 and their broad dissemination in oral surgery and dentistry since 1980 have resulted in basic changes in numerous diagnostic and therapeutic approaches. The medical use of lasers is of such an extent that it can well justifiably regarded as a new branch of science namely the laser medicine. This considerably relates to stomatology, too. PMID- 1291325 TI - [Conditions of successful endosseous dental implantations]. AB - The conditions of success of endosteal dental implants have been summarized on the base of the literature and own experiences. Three corresponding factors may determine the success: biocompatibility, biological seal, and the optimal force transfer. On the base of the data, the implantology is a biological way in the rehabilitation of edentulousness, if the conditions are kept in mind and are applied to the clinical practice. PMID- 1291326 TI - [Stomatologic implications of diseases of the locomotor apparatus]. AB - The authors describe rheumatic diseases with stomatological manifestations. There are some rheumatic diseases very frequently accompanied by oral symptoms. The author emphasize the importance of the cooperation between the rheumatologist and dentist in cases when the etiology of the stomatological changes is uncertain. PMID- 1291327 TI - [Free-end reconstruction by dento-osseous autotransplantation]. AB - The authors describe an endosseal autotransplantation A tooth is extracted together with its parodontium and the surrounding bone. It is implanted into a different place where the bone had been prepared. Upper left unilateral free-end saddle cases were solved by removing the tooth No 24 into the place of No 27. A bridge was constructed after 6 weeks using the 23 as abutment. The metal-ceramic bridges have been used by the patients for 3 years without complaint. PMID- 1291328 TI - [Clinical analysis of the sodium-fluoride and sodium-monofluorophosphate content of Colgate toothpaste]. AB - After six weeks use of Colgate toothpaste (1000 ppm MFP and 450 ppm NaF) in case of 50 individuals (25 test and 25 control persons) both the Plaque Index of Silness and Loe and the modified Sulcus Bleeding Index--"bleeding on probing" (Muhlemann and Son) mean values showed a significant decrease. According to the results of cytological testing the effect of toothpaste containing MFP and NaF proved favourable. The investigation of the ionisable plaque fluoride content produced statistically significant rise in plaque fluoride content. PMID- 1291329 TI - [Inclusion cysts. Case report]. AB - Inclusion cysts which are developmental anomalies can be seen either along the midpalatine raphe or on the dental ridges as well as on other areas of the palate in newborns. Based on their localisation and histology these are classified into three types (Epstein's pearls, Bohn's nodules, Dental lamina cysts). These are often taken as natal or neonatal teeth. No treatment is indicated since the lesions will spontaneously disappear few weeks after birth. PMID- 1291330 TI - [On the article "Dental status of young recruits in the light of a 15-year experience", by Vass and Harsanyi]. PMID- 1291331 TI - [Linear model of the pathogenesis of the temporomandibular pain-dysfunction syndrome]. AB - In the research of temporomandibular pain-dysfunction syndrome the etiological model of disease was created by a statistical system not applied until now. Of this it can be concluded that for the formation of the disease psychotic factors and oral parafunctions are responsible. Of the examination it became apparent that the cross sectional examination of the casual factors of the disease should be advisably carried out together with their correlations. PMID- 1291332 TI - [A rare case of contralateral "migration" of an impacted lower cuspid]. PMID- 1291333 TI - [Experience with the use of mini-plates in the surgical management of orbital frame fractures]. AB - The authors have reported about their experiences in the surgical treatment of orbital-frame. Champy plate osteosynthesis was performed in 11 cases for the surgical treatment of orbital frame fractures, which had considerably dislocation. The method is advised in the surgical treatment of middle-face fractures. PMID- 1291334 TI - [On the communications by Janos Szabo, Bela Herczeg, Jolan Banoczy and Imre Szabo]. PMID- 1291336 TI - [A case of Cushing's disease associated with a non-functioning adrenal tumor]. AB - A 52-year-old woman was admitted to our hospital for further examination of central obesity, hypertension and hirsutism suggesting Cushing's syndrome. Hirsutism had been remarkable for two years, and muscle weakness of the lower extremities gradually developed during the past year. CT scan revealed a tumor in the left adrenal gland which was 1 cm in diameter, round, well-circumscribed, homogeneous and not enhanced. Endocrine data disclosed increased urinary 17-OHCS (11.5-16.4 mg/day) and elevated plasma ACTH (125 pg/ml) and cortisol (19 micrograms/dl) with a lack of diurnal rhythm. Administration of the single-dose dexamethasone (1mg) did not suppress plasma cortisol. However, consecutive administration of either 2mg or 8mg of dexamethasone for 2 days suppressed both plasma cortisol and urinary 17-OHCS. Administration of metyrapone raised both urinary 17-OHCS and plasma ACTH levels. Rapid ACTH test resulted in a hyperresponse of plasma cortisol. CRF injection raised plasma ACTH and cortisol. Bilateral adrenal glands were well demonstrated by 19-iodocholesterol (I-131) scintigraphy during the administration of dexamethasone. MRI with Gd-contrast revealed a microadenoma in the sella turcica. With the diagnosis of Cushing's disease, the microadenoma was removed by the transsphenoidal approach and adrenal function was normalized. However, the left adrenal tumor remained on CT scan but was not demonstrated by scintigraphy. These findings indicate that this is a very rare case of Cushing's disease which was associated with an unilateral non functioning adrenal tumor. PMID- 1291335 TI - [Mechanism of renin release and cellular action of angiotensin II]. AB - Renin-angiotensin (RA) system plays an important role in cardiovascular homeostasis. Here, we have described the recent progress in our study of renin release as well as the cellular action of angiotensin II. (1) Microdissection of an isolated afferent artery with or without macula densa (MD) has revealed that renin release is regulated by NaCl exposure to MD. Furosemide, prostaglandins (PGE2 and PGI2) and adenosine modulate its function. (2) Angiotensin (ang) II increases cytosolic free calcium and induces the formation of inositolphosphates in vascular smooth muscle cells. Deduced protein structure of ang II receptor (AT1-R) cDNA has indicated the presumed link of AT1-R with phospholipase C. Through the cellular action, ang II has been reported to regulate gene expression. PMID- 1291338 TI - [A case of insulinoma with frequent hypoglycemic attacks not showing evident hyperinsulinemia]. AB - Confirmation of inappropriate hyperinsulinemia is an indispensable requisite for the diagnosis of insulinoma. We report here a case of insulinoma without evident hyperinsulinemia at an early stage. The patient, a 49-year-old woman, had been admitted to our hospital for the evaluation of frequent hypoglycemic attacks. At that time, plasma immunoreactive insulin (IRI) after an overnight fast ranged from 7 to 16 microU/ml. The ratio of IRI/fasting blood sugar (FBS) (Fajans index; normal range, below 0.3) was always between 0.13 and 0.28 even at hypoglycemic states. In addition, because computed tomography and arteriography of the abdomen failed to settle the diagnosis of insulinoma, the patient was discharged and followed up at our outpatient clinic for 2 years. She was admitted to our hospital at 51 years of age for the re-evaluation of hypoglycemic attacks. Laboratory examinations revealed high fasting plasma levels of IRI ranging from 20 to 29 microU/ml. Fajans index also increased to 0.47-0.89. Celiac arteriography was able to confirm the existence of insulinoma. We suggest that insulinoma should be considered in the presence of unexplained hypoglycemic attacks even when there is no evident hyperinsulinemia. PMID- 1291339 TI - [Studies on the production rate of estradiol in the testis in male infertility- studies of the predictive values on therapeutic efficacy in patients with oligozoospermia]. AB - It is surmised that studies on the relationship between the endocrinological milieu and therapeutic efficacy in male infertile patients are essential in elucidating the etiology of this disease and devising effective therapeutic methods. The relation between serum gonadotropin level and therapeutic efficacy has already been reported. In the present study, we investigated the basal levels of two sex steroids, i.e., testosterone and estradiol, and the estradiol:testosterone (E2/T) ratio, and also the increases in these parameters after the administration of hCG to human subjects presenting various degrees of testicular dysfunction, e.g., male infertile patients, aged males, Klinefelter's syndrome and hypogonadotropic hypogonadism. Special attention was given to the characteristics of the reserve capacity for secretion of estradiol in male infertile patients. The hCG test was performed on a total 527 subjects, including 65 normal adult males. The reserve capacity for the secretion of estradiol was investigated on the basis of the increasing rate in the serum E2/T ratio. The increasing rate in the serum E2/T ratio was statistically larger in subfertile males, oligozoospermia and azoospermia in comparison with the normal adult males. On the other hand, the aged males did not show any difference from the normal adult males, whereas the results were significantly lower in the male subjects with Klinefelter's syndrome and hypogonadotropic hypogonadism. It was considered that the increase in the serum E2/T ratio is one characteristic of the gonads of male infertile patients. The results of multiple regression analysis showed that the LH level, the pretreatment sperm concentration and the increasing rate in the serum E2/T ratio were important factors determining the increase in the sperm concentration after treatment. Accordingly, for cases of oligozoospermia characterized by an LH level of 13.7mIU/ml or less and a sperm concentration of 5 x 10(6)/ml or more, the relationship between the increasing rate in the serum E2/T ratio and therapeutic efficacy was investigated. It was found that the increasing rate in the serum E2/T ratio was significantly greater in the therapeutically ineffective cases compared with the therapeutically effective cases. On the basis of this finding, it was surmised that the percentage increase in the serum E2/T ratio is one index reflecting testicular function. In addition, for cases of oligozoospermia characterized by an LH level of 13.7mIU/ml or less, a sperm concentration of 5 x 10(6)/ml or more and the increasing rate in the serum E2/T ratio of 4.01 or less, the relationship between the degree of spermatogenesis and therapeutic efficacy was investigated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1291337 TI - [The mechanism of glucose intolerance in patients with Graves' disease]. AB - To investigate the mechanism of glucose intolerance in patients with Graves' disease, a 2-hour oral glucose tolerance test and euglycemic glucose clamp study using Biostator were performed in patients with Graves' disease and control subjects. 80 per cent of the patients showed impaired glucose tolerance. Insulinogenic index in the patients with borderline or diabetic glucose response was lower than that in subjects with normal glucose response. Insulinogenic index was inversely correlated with sigma PG during the test. Despite normal basal plasma glucose concentrations, basal plasma insulin levels in the patients with Graves' disease were higher than in the controls. Using the euglycemic glucose clamp technique, the glucose utilization rate (M value), the metabolic clearance rate of glucose (MCRG) and the insulin sensitivity index (M/I x 100) in the patients with Graves' disease were lower than in the controls. After treatment with antithyroid drug in 3 patients, glucose tolerance completely normalized, and there was a significant increase in the M value and the MCRG and a significant decrease in the metabolic clearance rate of insulin (MCRI) compared to the values before treatment. In the patients with Graves' disease, basal serum glucagon levels were higher than in the controls, and glucagon suppression during insulin infusion was found to be decreased. From these data, it is concluded that the decrease in glucose tolerance in patients with Graves' disease can be explained by 1) the impairment of early insulin release response to rapid intestinal glucose absorption, 2) increased insulin metabolic clearance and 3) hyperglucagonemia. PMID- 1291340 TI - [A case of esophageal carcinoma with hypercalcemia caused by PTH-rP--the effect of therapy on the bone and calcium metabolism]. AB - The changes in the bone and in calcium metabolism during cisplatin or bisphosphonate administration is reported in a 50-year-old patient with esophageal carcinoma who had humoral hypercalcemia of malignancy (HHM). Laboratory findings on admission showed that ionized calcium was 1.65mmol/L, phosphorus was 2.4mg/dl, and PTH-rP was 151pmol/L, without any evidence of bone metastasis. After admission, cisplatin and/or bisphosphonate were administrated for hypercalcemia. These administrations ameliorated serum ionized calcium, urinary pyridinoline and hydroxyproline level within a few days. Although cisplatin administration decreased the serum osteocalcin level, bisphosphonate administration kept up the level, suggesting that bisphosphonate maintained bone formation and cisplatin decreased its formation. The discrepancy may be due to the coupling with the reduction of bone resorption and/or direct toxic effect on osteoblasts during cisplatin administration, and preservation of osteoblastic activity during bisphosphonate administration. Cisplatin and bisphosphonate may have different effects on bone formation. Serum 1,25(OH)2D level was slightly decreased or unchangeable after cisplatin administration, although the level was increased after bisphosphonate administration. Direct toxic effect on 1 alpha hydroxylase of the kidney or increase in phosphrous level may explain the change of 1,25(OH)2D after cisplatin administration. These results suggested that cisplatin and bisphosphonate have the same effect of preventing bone resorption but different effects on bone formation and/or serum 1,25(OH)2D level. PMID- 1291341 TI - Esbiothrin-impregnated ropes as mosquito repellent. AB - Esbiothrin [(+/-)-3-allyl-2-methyl-4-oxocylopent-2-enyl-(+)-trans- chrysanthemate] is an improved isomeric composition of allethrin series and consists essentially of esters of chrysanthemic acid and allethrolone. Jute rope was impregnated with esbiothrin and the smoke from smouldering ropes was evaluated as mosquito repellent in human dwellings and cattlesheds with open doors and windows at different dosages. Esbiothrin-impregranted (500 ppm) ropes prevented the entry of more than 95% An. culicifacles and other anophelines, 90.9 88.8% Culex quinquefasciatus and 96-95.1% total mosquitoes in open rooms of houses and cattlesheds respectively. The impact of ropes was more pronounced on the biting rate of mosquitoes. Indoors and outdoors human baits seated at a distance of about 3 m from smouldering esbiothrin ropes experienced no bite at all from An. culicifacies. An iron mesh around the rope prevents fire hazards. PMID- 1291342 TI - Sensitivity status of Plasmodium falciparum to chloroquine, amodiaquine, quinine, mefloquine and sulfadoxine/pyrimethamine in a tribal population of District Sundargarh, Orissa. AB - In a malaria-endemic area of Orissa, wherein chloroquine has been in use for over thirty years, 58.3% (14/24) P. falciparum cases did not respond to single dose chloroquine (10 mg base/kg) in in-vivo test. With standard dose (25 mg base/kg) 31.2% cases (10/32) showed resistance, i.e. at RI (15.6%), RII (9.4%) and RIII (6.2%) levels. Standard dose was superior in response to the single dose therapy [p < 0.05; chi 2 (df 1) = 4.11]. Out of eight isolates tested in vitro, two showed resistance to chloroquine, five to sulfadoxine/pyrimethamine (SP) but all were sensitive to amodiaquine, quinine and mefloquine. Whereas the standard dose of chloroquine would be a better option in general, in resistant cases, SP, quinine and mefloquine offer an alternative drug choice. The implications of drug resistance in a malaria-control programme and the need to revise drug policy in India are discussed. PMID- 1291343 TI - Malaria epidemic in Baniyani village, District Farrukhabad (U.P.). AB - Many deaths were recorded in village Baniyani of Talgram PHC of District Farrukhabad, U.P. during August to November 1991, which is the malaria transmission season in this area. Integrated measures, like one-round spraying of DDT and HCH, six-round fogging of malathion and six-time application of Baytex in mosquito breeding sites, were adopted by the Health Department of the U.P. government to avert an epidemic. Investigations carried out by the Malaria Research Centre during November and December 1991 showed low mosquito densities and larval positivity but very high incidence of malaria in the village. No malaria case was recorded by the surveillance worker of the Health Department of the state government before the outbreak of the disease. However, high slide falciparum rate (51.57), child parasite rate (40.0), infant parasite rate (66.66) and spleen rate (82.90) in the village clearly indicated hyperendemic conditions in the area and hence deaths recorded in the village during the malaria transmission period could be due to malaria only. Major factors responsible for the deaths due to malaria in the village were poor surveillance, faulty diagnosis, and low literacy and socio-economic status of the villagers. PMID- 1291344 TI - Frequency of ABO blood groups, sickle-cell haemoglobin, G-6-PD deficiency and their relation with malaria in scheduled castes and scheduled tribes of Kheda District, Gujarat. AB - Frequency of sickle cell in Scheduled Caste and Scheduled Tribe populations was found to be 1.5 and 14.9% respectively, whereas G-6-PD deficiency was 5.9 and 4.2% respectively. Blood group B was dominant in both the communities. A significantly lower frequency of P. falciparum malaria was observed among sicklers. PMID- 1291345 TI - Malaria and ABO blood groups. AB - Subjects from Muria gond tribal community (n = 258) as well as from Delhi (n = 100) were classified according to ABO blood groups, and were also assayed for malarial antibodies by ELISA technique. The distribution of ABO blood groups did not differ significantly in Muria gonds and Delhi subjects. Within Muria gonds the observed frequency of ABO blood groups did not differ significantly from the expected values. No significant difference was observed in the rate of seropositivity for malarial antibodies among subjects with different blood groups. Malarial parasitaemia, although observed more in individuals with blood group A, did not differ significantly as compared with other blood groups. We conclude that ABO blood groups do not show differential susceptibility to malaria. PMID- 1291346 TI - Note on urban malaria vector Anopheles stephensi (Liston) in cochin. PMID- 1291347 TI - Sensory impairments. PMID- 1291348 TI - Bleeding as an indicator of health or disease. PMID- 1291349 TI - The role of a hygienist in a research team. PMID- 1291350 TI - Oncology here and there: the role of the hygienist. PMID- 1291351 TI - Living with lasers. PMID- 1291352 TI - Carpal tunnel syndrome. Risk factors and preventive strategies for the dental hygienist. AB - Carpal tunnel syndrome (CTS) is well recognised as an occupational risk for dental hygienists. The contributing risk factors fall primarily into two categories: medical and occupational. The purposes of this paper are to examine the factors that predispose one to CTS in order to increase awareness among dental hygienists, and to offer preventive strategies that can be incorporated into daily practice. PMID- 1291353 TI - The immune response to oral infections. AB - This article summarizes some of the important interactions between the immune system and inflammatory process, with the primary focus on the host response to infection. A subsequent brief review of the pathogenesis of periodontal disease serves to illustrate the relevance of these interactions to our understanding of disease. PMID- 1291354 TI - Resin-Bonded bridges: 1. Development and casting design. AB - This series of two articles will consider the developments and clinical techniques of resin-bonded bridges with the emphasis on methods for increasing success from a functional and aesthetic view point. PMID- 1291355 TI - Update on periodontology: 2. Diagnosis in periodontology. AB - The second in this series of articles looks at the problems of diagnosis in periodontology. This is an area that is often neglected in the routine examination of patients, but with the introduction of systems like CPITN the examination of patients with periodontal disease is becoming easier. PMID- 1291356 TI - The diagnosis of dental caries: 3. Rationale and overview of present and possible future techniques. AB - A number of changes have taken place recently which may influence a practitioners choice of diagnostic methods for detecting and monitoring dental caries. The first two articles described the use of current diagnostic methods at various specific sites. This third paper discusses the rationale behind the use of these techniques and provides an overview of present techniques and those which may be useful in the future. PMID- 1291357 TI - Selecting a health meritocracy. PMID- 1291358 TI - Hemisection: a treatment option for the vertically split tooth. AB - As the population keeps their teeth longer the problem of tooth fracture and severe fracture of the root is becoming increasingly significant for the restorative dentist. This paper discusses hemisection, an alternative to extraction in cases of vertical root fracture in patients capable and willing to carry out proper oral hygiene measures. PMID- 1291359 TI - Smoking kills. PMID- 1291360 TI - Oral care of the HIV-infected patient. AB - There are only a small number of specialized centres that cater for the dental care of the steadily increasing number of HIV-infected individuals. The responsibility will, therefore, be increasingly shared with the dental practitioner who should be knowledgeable on the basic oral management protocols involved in treating these individuals. This article summarizes some essentials of oral health care in HIV-infected individuals. PMID- 1291361 TI - Sedation in dental practice. AB - The recent publication of the Department of Health's report from the Expert Working Party on General Anaesthesia, has made recommendations on sedation in the dental practice. This article discusses the use of benzodiazepines by the general dental practitioner. PMID- 1291362 TI - The specific plaque hypothesis and the antimicrobial treatment of periodontal disease. AB - According to the specific plaque hypothesis a measurable amount of periodontal disease is due to the overgrowth of specific bacterial types. The author advocates the theory and discusses treatment. This includes techniques for diagnosing the predominant bacterial types, antibiotic therapy and the relevance of regular debridement. PMID- 1291363 TI - Quality assurance: 1. Reject analysis, operator technique and the X-ray set. AB - Number 1 of the series, which will present the 'core knowledge' on radiography, is designed to help the dentist produce the highest quality radiographs and appears in two parts. Part 1 discusses the identification of problems and how to solve those related to operator technique and the X-ray set, while part 2 will comment on problems with the image receptor, the darkroom and processing. PMID- 1291364 TI - Resin-bonded bridges: 2. Treatment planning, clinical gases and failures. AB - This is the second paper in the two-part series which considers the developments and clinical techniques of resin-bonded bridges with the emphasis on methods for increasing success from a functional and aesthetic view point. Part 1 focused on the development and types of resin-bonded bridge and tooth preparation. This article describes the clinical application of this type of bridge and discusses failures. PMID- 1291365 TI - Post-endodontic pericoronitis. AB - Pericoronitis is defined as inflammation of the soft tissue around the crown of any partially erupted tooth. A case of pericoronitis with an unusual aetiology is described. PMID- 1291366 TI - Food and oral health: 1. Dental caries. AB - Dental schools tend to teach only the rudiments of this subject and this does not provide a good basis for dentists to advise patients and combat the misinformation surrounding the topic. The first article in the two-part series examines nutrition as it applies to dental caries, while part two will discuss some of the general principles of nutrition in relation to oral health, periodontal disease and the oral mucosa. PMID- 1291367 TI - Aesthetic brackets: to perfect or to reject? AB - Orthodontists are now treating patients who are demanding high quality orthodontics which is also aesthetically pleasing. The quest for an aesthetic yet strong appliance has led to many innovative designs. This article summarizes the main advances. PMID- 1291368 TI - Lasers in dentistry. AB - Lasers, which are constantly evolving, can be customized to meet dental requirements and could become a very useful tool for dental practitioners. The article provides an introduction to the instruments, which includes a description of how they work and discusses their applications in dentistry. PMID- 1291369 TI - Quality assurance: 2. The image receptor, the darkroom and processing. AB - Number 1 of the series, which presents the 'core knowledge' on radiography, is designed to help the dentist produce the highest quality radiographs and appears in two parts. Part 1 discussed the identification of problems and how to solve those related to operator technique and the X-ray set, whilst this article will comment on difficulties with the image receptor, the darkroom and processing. PMID- 1291370 TI - Dental practitioner attendances at postgraduate courses in a dental school 1988 90. AB - The attendance pattern of dental practitioners who resided in the West Midlands on postgraduate courses at Birmingham University Dental School was studied over a two-year period. This paper provides an insight into the trends occurring in postgraduate training in this area. PMID- 1291371 TI - Tongue in cheek. AB - Apyogenic granuloma is an innocent lesion commonly found on the gingiva, but can occur at other oral sites. A case is reported of a tongue lesion which had been present for 20 years and is unusually large. PMID- 1291372 TI - Heading for the USA? PMID- 1291373 TI - Quality, efficiency and statistics in a reformed NHS. PMID- 1291374 TI - Management of oral complications following radiotherapy. AB - Radiotherapy for the treatment of neoplastic disease in the head and neck region results in a number of oral changes liable to cause pain and discomfort during therapy. In the longer term, it increases the patient's susceptibility to caries and periodontal disease. The aim of this paper is to outline these changes and to suggest a regime for the dental management of these patients before, during and after radiotherapy. The role of the dentist in support, advice and treatment is vital. PMID- 1291375 TI - The use of dental amalgam--an art or a science? AB - Dental amalgam remains the best material for filling teeth when aesthetics are of secondary importance. Over the last 20 years improvements in the composition have reduced marginal failure due to creep and corrosion, and the use of modern adhesives has lead to an early seal between the tooth and the filling. However, the proper handling by the dentists remains as the cornerstone for fillings that are going to last. This article describes the history, classification, structure and handling variables of dental amalgams. It also discusses the effects of extra elements, bonding agents and the possible hazard of mercury. PMID- 1291377 TI - Dental demolition. AB - A proportion of our chairside time is spent in replacing defective restorations. However, many of the well known textbooks on restorative dentistry describe how high quality restorations should be produced, but not the techniques for removing faulty ones. This article discusses some of these techniques. It examines the removal of nonadhesive and adhesive plastic restorations, veneers, inlays, root fillings, crowns and bridges. The removal of foreign objects and posts from root canals has been described elsewhere and so will not be discussed here. PMID- 1291376 TI - Selected issues on care and management of the ageing patient: 2. Prevention and treatment. AB - The elderly are a vulnerable group of patients in whom even simple dental care can become invasive and require the use of a local anaesthetic. Part 1 assessed the factors which may influence the ability of the patient to receive treatment and established treatment priorities. It also described the particular problems that may arise when dealing with the elderly and indicated the adjustments of a practice which would help in the care of these patients. Part 2 will now discuss prevention and treatment. PMID- 1291379 TI - Stress and the triangle of needs in dental practice. PMID- 1291378 TI - Glove wearing by dental surgery assistants in general practice: results of a survey. AB - Cross-infection routines should be used by both the dentist and the dental surgery assistant (DSA), and the wearing of gloves during patient treatment is considered an integral part of such routines. Results are presented which indicate the extent to which DSAs wear gloves while assisting in patient care, and the factors influencing glove wearing are discussed. PMID- 1291380 TI - Electrosurgery in restorative dentistry: 1. Theory. AB - Electrosurgery techniques have been used in dentistry as an aid to soft tissue management for nearly 60 years. However, it was not until the late 1960s that the principles of electrosurgery were understood and improved equipment became available. Part 1 of this two-part series covers the theory behind using this technique. Part 2 will discuss the clinical applications. PMID- 1291381 TI - Alternatives to gold. AB - Despite, or perhaps because of, its antiquity the lost wax casting process which we use in dentistry still produces the most accurate and durable restorations in our armamentarium. Although high-gold content alloys still act as the benchmark of quality, fit, and durability in the aggressive conditions of the mouth, their inherent cost, high density and low modulus have stimulated a search for alternatives. This has ranged widely through the metallurgical world and across the periodic table of the elements. As a result dental alloys for casting into inlays, crowns and bridges (with or without facings of dental porcelain) have become incredibly complex. This article will explain some of the reasons behind the developments. PMID- 1291382 TI - Advances in fixed appliance design and use: 2. Auxiliaries, adhesives, appliance care and debonding. AB - Many new developments in design and materials have made it easier for orthodontists to produce good results with fixed appliances in a shorter time. Orthodontic treatment has also become more comfortable and aesthetically pleasing for patients. This is the second of two papers which are intended to provide an update on fixed appliance design and use, so patients can be informed of relevant advances before they are referred to a specialist for orthodontic advice. Part 1 discussed the development in brackets and archwires. Part 2 will now cover recent advances in ligatures and elastomeric ties, intraoral auxiliaries, adhesives, products to assist oral hygiene and prevention during fixed appliance treatment, and new methods of debonding. PMID- 1291383 TI - Effective periodontal control. AB - One of the major difficulties in periodontal care is that knowing the principles is of very little practical help when it comes to treating individual patients. This article discusses the identification of susceptible patients, the measurements of sites of disease and identification of active bursts of disease when the patient is on a maintenance programme that can be easily performed by the dental practitioner. PMID- 1291384 TI - Clinical aspects of occlusion: 1. Occlusal terminology and the conformative approach. AB - This two-part series aims to familiarize the reader with essential occlusal principles and terminology and to give some guidelines as to which cases are suitable for crown and bridgework. The first article covers occlusal terminology and the conformative approach, whilst the second will describe the reorganized approach. Both papers contain clinical cases which demonstrate how to overcome some of the occlusal problems encountered in this area. PMID- 1291385 TI - Another accessory root on a maxillary incisor. PMID- 1291386 TI - Major aphthous ulcer presenting as a carcinoma. PMID- 1291387 TI - Subsurface deformation associated with hardness measurements of composites. AB - This study was prompted after a series of composites had been hardness-tested with the Vickers (pyramidal diamond indenter) and Barcol tests (flat-ended steel cone indenter). The results were found to differ markedly from the supplied Barcol/Vickers conversion chart. A sectioning and silver staining technique was therefore developed to examine the modes of subsurface deformation of four composites under the two indenters. Under the Vickers indentations, the large particle hybrid, Occlusin, showed a clear hemispherical area of subsurface disruption while the small particle hybrid, Brilliant Dentin, had a less distinct zone of disruption. The microfilled materials, Heliomolar and Isosit, showed minimal silver uptake, suggesting a less disruptive mode of plastic deformation. Under the Barcol indentations, Occlusion and Brilliant Dentin produced clear hemispherical zones of deformation, while Heliomolar and Isosit were badly crazed with distinctive patterns of subsurface flaws. These consistent patterns of failure to some extent explain the comparison of hardness measurements and may be of use in explaining the wear mechanisms of composite restorations. PMID- 1291388 TI - Dentin thickness, hardness, and Ca-concentration vs bond strength of dentin adhesives. AB - The relationship between the tensile bond strength (TBS) and three dentin characteristics: remaining dentin thickness (RDT), Ca-concentration, and hardness, were investigated. Sixty-two extracted bovine incisors, divided into four groups, were prepared using 600-grit SiC paper to create flat dentinal surfaces. The materials tested in this study consisted of three commercially available and one experimental dentin bonding systems. The TBS and modes of failure were determined after storage for 24 h in 37 degrees C water. Then RDT, Ca-concentration, and hardness were measured. Data were statistically compared with TBS of each group. The mean bond strength of the commercial materials ranged from 2.5 +/- 0.9 MPa to 7.7 +/- 2.8 MPa. Correlations with Ca-concentration and RDT varied, depending on the product. The bond strength of the experimental material was 9.2 +/- 4.4 MPa and significantly correlated with RDT and hardness. With two of the dentin bonding agents, specimens showed a high number of cohesive fractures in dentin, 40% to 82%. It was concluded that the variability of TBS was influenced by dentinal characteristics in three of the four materials tested. PMID- 1291389 TI - A new light-activated adhesive composite: shear bond strength and microleakage. AB - A new light-activated adhesive composite has been formulated. Its shear bond strength and marginal microleakage were compared with glass ionomer cements: Fuji Ionomer Type II, Ketac-Fil and Ketac-Bond. The new material showed significantly (p < 0.05) higher bond strength to non-etched enamel (7.9 MPa) and dentin (7.3 MPa) than commercially available materials. It also performed significantly better (p < 0.05) in the microleakage test. Ease of use and the excellent marginal sealing ability of the new material are expected to allow considerable innovation in restorations of root caries, cervical erosion and other conditions where the marginal seal of the gingival cavosurface is difficult. PMID- 1291390 TI - The influence of surface conditions and silane agents on the bond of resin to dental porcelain. AB - The influence of porcelain surface condition and the application of silane agents on the adhesion between resin and dental porcelain were investigated. The experimental variables included three porcelain surface preparations, as polished, etched with phosphoric acid, or etched with hydrofluoric acid and three kinds of commercially available silane coupling agents. The shear bond strength between the light-cured composite and the dental porcelain was measured after one day immersion in 37 degrees C water. Samples without the silane agent application were also tested as controls. Without the silane agent, hydrofluoric acid-etched specimens had a higher bond strength than polished or phosphoric acid-etched specimens. The combination of hydrofluoric acid-etching and an application of Cosmotech Porcelain Primer increased the bond strengths more than that of phosphoric acid-etching. With the application of Laminabond Porcelain Primer or Optec Silane Coupling Agent, high bond strengths were obtained regardless of the porcelain surface condition. Therefore, it seems the chemical reactions between the porcelain surface and silane agents were responsible for the high shear bond strengths. PMID- 1291391 TI - Corrosion testing by potentiodynamic polarization in various electrolytes. AB - The effect of different electrolytes on the results from potentiodynamic polarization corrosion testing was studied for nine different dental alloys. In general, the difference in the results was greater between certain alloys using the same electrolyte than between the electrolytes with the same alloy. However, there were some differences between the electrolytes, most pronounced when testing dental amalgams. The electrolyte consisting of 1% NaCl seemed to offer the most corrosive environment. Darvell's and Fusayama's solutions were much less corrosive, at least for dental amalgam specimens. With regard to the ranking by corrosion sensitivity of the amalgams, only the results obtained by using Fusayama's solution were consistent with the clinical experience of the materials. PMID- 1291392 TI - Clinical evaluation of four anterior composite resins over five years. AB - Four hundred and thirty nine chemical-cured composite resin restorations were placed in the anterior teeth of 86 patients treated in a private dental practice. Four anterior resins were used, and placement was performed with acid etching and appropriate enamel bonding resins. Assessments were made of the handling characteristics, condition of the gingiva, surface staining, marginal staining, color deterioration, and of the longevity of the four materials. Clinical deterioration rates and failures of the different types of composites were evaluated over periods of up to five years. Although all the assessed clinical factors deteriorated with time, there were very few unsatisfactory rating scores. Most of the composite restorations performed well over the study. Eight per cent of the restorations failed during the study. Class IV preparations showed the highest restoration failure rates. PMID- 1291393 TI - An in vitro comparative analysis: scanning electron microscopy of dentin/restoration interfaces. AB - One hundred maxillary premolar teeth were randomly allocated to ten groups. Each group was restored with one of ten different restorative techniques. The teeth were stored in deionized water for 7d prior to longitudinal sectioning in a mesio distal plane. Following sectioning, ten specimens from each group were chosen at random from the 20 available sections. The sectioned surfaces were polished using 600-grit SiC abrasive paper and etched for 10 s with 50% phosphoric acid to remove the smear layer produced by sectioning. Five tooth sections from the dentin bonding resin groups were allowed to dry at 20 degrees C for 24h. The glass ionomer-based groups were reimmersed in deionized water during this period. The remaining five sections from each group were replicated using an addition cure vinyl polysiloxane impression material and an epoxy resin. A comparison was made of the sections and the replicas. All tooth specimens were sputter-coated with gold for 4 min and examined using a scanning electron microscope. Replicas were gold-coated for 3 min. Different tooth/restoration interfaces, associated with different materials, were observed. A marked difference between the replicas and tooth sections was observed for glass ionomer-based restorations but not for resin-based bonding systems. Representative samples of replicas and specimens are shown, and the significance of the observed differences is discussed. PMID- 1291394 TI - Dentin adhesion of "modified" 4-META/MMA-TBB resin: function of HEMA. AB - This study investigated adhesion to dentin of a modified 4-META/MMA-TBB resin (4 methacryloxyethyl trimellitate anhydride in methyl methacrylate initiated by tri n-butyl borane) which does not require PMMA powder to polymerize. Ground bovine dentin specimens were pre-treated with an aqueous solution of 10% citric acid and 3% ferric chloride (10-3). This solution removes the smear layer and demineralizes the dentin, exposing collagen. Improved bond strengths were obtained when a HEMA-primer was applied to 10-3 pre-treated dentin. SEM examination revealed the formation of a transitional zone of resin-reinforced dentin (hybrid layer) in 10-3 pre-treated, HEMA-primed samples. The adhesive monomer impregnated exposed collagen fibrils and, upon polymerization, became entangled with them to create the hybrid layer, essential in achieving significantly high tensile bonding strengths. HEMA enhanced the penetration capability of dentinal substrates. After polymerization and formation of the hybrid layer, auto-cured acrylic resin, photo-cured composite and amalgam were all capable of adhering to the dentin. The modified 4-META/MMA-TBB resin created significant adhesive bonds to 10-3 pre-treated ground bovine dentin. PMID- 1291395 TI - Influence of selected variables on adhesion testing. AB - Three variables associated with adhesion testing were examined: (1) the test mode, shear and tension; (2) design of the tensile apparatus; and (3) tooth substrate, human and bovine. Findings revealed no significant differences in bond strength by one tensile test and a shear test. However, the shear test produced more true adhesive failures; thus it may be preferable to use a shear test for adhesion testing. Bond strengths with some adhesive systems differed significantly when tested by two different tensile apparatus. Design of the test apparatus appeared to affect values. Bond strength measurements obtained with human and bovine enamel were essentially comparable. Values with dentin varied. There appeared to be a trend for higher bond strength values with bovine than with human dentin. PMID- 1291396 TI - Evaluation of methylene lactone monomers in dental resins. AB - alpha-Methylene-gamma-butyrolactone (MBL), which can be described as the cyclic analog of methyl methacrylate, exhibits greater reactivity in free radical polymerizations than conventional methacrylate monomers. Unfilled resin formulations composed of Bis-GMA/MBL or Bis-GMA/TEGDMA/MBL were light-cured. The effect of the more reactive methylene lactone monomer on mechanical properties and the degree of conversion of the polymers was examined. The infrared absorption bands for the carbon-carbon double bonds of MBL and the methacrylate monomers are well resolved and allow the conversion of each component to be calculated individually. The incorporation of a small amount of MBL (5 w/o) to Bis-GMA significantly increased the conversion; however, additional MBL (10 to 30 w/o) did not further increase the Bis-GMA conversion level. This appears to indicate an incompatibility between MBL and the bulky Bis-GMA monomer. Addition of 10 w/o MBL to Bis-GMA/TEGDMA (7:3) resulted in a cured resin with 71% methacrylate and 75% overall conversion efficiencies compared with the 57% conversion of the control formulation. The diametral tensile and the transverse strengths were approximately 10% greater for the MBL resin compared with the Bis GMA/TEGDMA control; however, these differences were not statistically significant. The synthesis and polymerization of several substituted methylene lactones was also studied. PMID- 1291397 TI - A comparison of monomer conversion and inorganic filler content in visible light cured denture resins. AB - Visible light-cured (VLC) denture resins are relatively new products used for the reline and repair of dentures. The conversion of monomer into polymer in 3 brands of visible light-cured denture resins was investigated. The relationship of the inorganic filler content to this conversion was also studied. It was determined that these reline materials vary in monomer conversion and weight percentage of filler, and this variation is brand dependent. The monomer conversion ranged from 77% to 97%. Significant differences in these values were found when duration of light exposure was increased. In addition, resin nearest to the light source polymerized to a greater extent when compared to resin that was 1 mm deep to this surface, hence furthest from the light source. The inorganic filler content ranged from 0% to 15%. For the resin systems studied, the relationship between monomer conversion and inorganic filler loading was inversely proportional. Results indicated that monomer conversion of VLC repair resins was affected by the duration of light exposure as well as the amount of inorganic filler present in the material. PMID- 1291398 TI - Effects of surface-active resins on dentin/composite bonds. AB - Effective dentin bonding systems based on para-PMDM diadduct of pyromellitic dianhydride and 2-hydroxyethyl methacrylate (HEMA) have been developed (Bowen et al., 1982). Para-PMDM, a solid of limited solubility, is usually applied from an acetone solution to dentin that has been preconditioned with acid and N phenylglycine. The feasibility of using a liquid, surface-active bonding resin to substitute for or to supplement para-PMDM was explored. Mono(2 methacryloyloxy)ethyl phthalate (MMEP), a liquid, monofunctional homolog of para PMDM (derived from the reaction of phthalic anhydride with HEMA) was used to formulate several bonding resin systems and solutions. Dentin surfaces were pretreated according to several variations of a three-step bonding protocol involving sequential application of 6.8 w/o ferric oxalate in 2.5 w/o HNO3, N phenylglycine in acetone, and an experimental bonding resin before placement of a chemically cured composite restorative material. Tensile bond strengths were tested after 24 h storage in distilled water at 23 degrees C. The results suggest that solutions based on MMEP and/or para-PMDM in acetone or in other monomers, especially those containing HEMA, can effectively promote bonding to dentin. A new mechanism for the observed self-polymerization of MMEP or para-PMDM with N phenylglycine is proposed. PMID- 1291399 TI - The Weibull distribution applied to post and core failure. AB - In this study, data on initial failure loads of direct post and core-restored premolar teeth were analyzed using the Weibull distribution. Restorations consisted of a prefabricated titanium alloy post, and an amalgam, composite or glass cermet core buildup in human upper premolar teeth. The specimens were subjected to compressive forces until failure at angles of 10, 45 and 90 degrees to their long axis. The two- and three-parameter Weibull distributions were compared for applicability to the failure load data. For estimation of the parameters of the two-parameter distribution: sigma 0 (reference stress) and m (Weibull modulus), linear regression was used. In this distribution, it is assumed that the third parameter, sigma u (cut-off stress), equals 0. The Maximum Likelihood (MLH) method was used to estimate all three parameters. It was found that the choice of distribution has a strong influence on the estimated values and that the three-parameter distribution is best fitted for the failure loads in this study. Comparisons were made between the failure probability curves as found by MLH estimation for the different core materials and loading angles. The results indicated that the influence of loading angle on the failure mechanism was stronger than that of core material. PMID- 1291400 TI - Non-steroidal anti-inflammatory drugs inhibit the processes of mucosal cell proliferation associated with duodenal ulcer healing. AB - We demonstrate that, in patients taking non-steroidal anti-inflammatory drugs (NSAIDs), there is inhibition of the proliferation of mucosal cells that normally leads to healing of duodenal ulcers. A microdissection technique was used to quantitate mitosis in duodenal crypts at the ulcer edge, giving a regeneration index of mitotic rate at that site, as compared to nearby mucosa. In patients with duodenal ulcers occurring in the absence of NSAID therapy, there was a brisk regenerative response (median index 2.48, range 1.55-9.81, n = 8), significantly greater than in patients taking NSAIDs (median index 1.10, range 0.73-2.16, n = 10, p = 0.014). Inhibition of the process of epithelial cell division normally involved in duodenal ulcer healing could contribute to the delay in ulcer healing which may explain the higher complication rate for duodenal ulcer during NSAID therapy. PMID- 1291401 TI - Antimicrobial therapy of bacterial diarrhea in adult residents of Mexico--lack of an effect. AB - Two clinical trials in adults in Mexico are reported. In the first trial, long term residents of Mexico with acute fecal leukocyte-positive diarrhea were randomized to receive trimethoprim/sulfamethoxazole (TMP/SMX), clioquinol or a placebo. Neither antimicrobial shortened the illness for all cases or for those with shigellosis or enterotoxigenic Escherichia coli diarrhea. In a second study, US and Mexican students received enoxacin, TMP/SMX or a placebo on a blind random basis. While the placebo-treated subjects with bacterial diarrhea tended to be more ill after treatment than other groups, no statistical differences were seen in treatment groups. These studies cast doubts on the value of antimicrobial drugs for 'invasive' and other forms of bacterial diarrhea in adults living in endemic areas and indicate the importance of a placebo control group when conducting clinical trials in these populations. PMID- 1291402 TI - Use of an ammonia electrode for rapid quantification of Helicobacter pylori urease: its use in the endoscopy room and in the assessment of urease inhibition by bismuth subsalicylate. AB - The use of an ammonia electrode to quantify ammonia liberated by urease from Helicobacter pylori was assessed in an in vitro study. It was found to be highly sensitive (down to 0.7 ppm NH3) and highly reproducible (coefficient of variation 6.0%). Inhibition of urease by bismuth subsalicylate was evaluated as urease testing is often used to assess clearance of H. pylori in patients treated with bismuth. Concentrations of bismuth subsalicylate up to 5 mg/ml had no inhibitory effect but bismuth subsalicylate at 50 mg/ml resulted in 21% inhibition of the urease activity of an ultrasonicated H. pylori suspension. As a preliminary study, the ammonia electrode was assessed in the endoscopy room in comparison with conventional techniques for H. pylori diagnosis. Antral biopsies from 39 patients attending for routine diagnostic endoscopy were subjected to culture, histology, detection of urease activity with a commercially available slide test (CLO) and with the ammonia electrode to detect ammonia liberated from samples placed in urea solution. 21 patients were positive after 1 h with the ammonia electrode, compared to only 17 with the commercially available slide test. 20 were positive on histology and 19 by culture. All samples positive with the ammonia electrode were either positive by culture or by histology. The ammonia electrode offers a quick, sensitive, quantitative and cheap method for the detection and quantification of H. pylori. PMID- 1291404 TI - A clinical and laboratory evaluation of the behavior of tissue polypeptide antigen in liver cirrhosis. AB - Serum tissue polypeptide antigen (TPA) was determined in 86 cirrhotic patients who underwent a thorough clinical and laboratory evaluation. Increased serum TPA levels were found in 87.2% of the patients (81% of Child's A, 81.3% of Child's B and 97% of Child's C) with very high levels in some cases. There were significant correlations between TPA and several clinical and biochemical tests, especially AST (r = 0.678, p < 0.000001), and this enzyme was the best predictor of TPA levels. Patients with abnormal AST had also significantly higher serum levels of TPA than those with normal AST in each of the Child's class (p < 0.01 for each). TPA values were found to be more frequently abnormal than AST ones in cirrhotics (p = 0.009) and could be used as indirect markers of activity in these patients. The underlying mechanism involved in the increase in TPA in cirrhosis was probably related to the cytolytic/regenerative activity of the liver. TPA cannot be used as a tumor marker in these patients. PMID- 1291403 TI - Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach. AB - The effects of serotonin and its related compounds on immunoreactive thyrotropin releasing hormone (ir-TRH) concentrations of the rat stomach wall and gastric juice were studied. Either serotonin, cyproheptadine or GR38032F was injected intraperitoneally, and the rats were decapitated at various times after the injection. ir-TRH concentrations of the stomach wall and gastric juice were measured by radioimmunoassay, and gastric serotonin concentrations were measured by HPLC. ir-TRH concentrations of the stomach wall decreased, and ir-TRH concentrations of gastric juice increased significantly after serotonin injection. On the other hand, both cyproheptadine and GR38032F did not affect ir TRH concentrations of the stomach. The effects of serotonin on ir-TRH concentrations of the stomach were significantly blocked by the pretreatment of cyproheptadine and GR38032F. The reciprocal changes of gastric ir-TRH and serotonin concentrations were observed without changes in gastric juice pH. These findings suggest that serotonin stimulates ir-TRH release from the stomach wall into gastric juice, and the effects of serotonin on ir-TRH release may be partly mediated via 5-HT2- and 5-HT3-receptors. PMID- 1291405 TI - Comparison of once-daily intravenous and oral omeprazole on pentagastrin stimulated acid secretion in duodenal ulcer patients. AB - The effect of 5 days of once-daily dosing with 20 mg p.o. and 40 mg i.v. omeprazole on pentagastrin-stimulated acid secretion was studied in 8 patients with duodenal ulcer. In addition they also received a 10-mg i.v. dose on day 6 during the oral treatment period. The antisecretory effect was measured 6-7 h after dose at a time point when maximal inhibition during the dosing interval is anticipated. The median percent inhibition of peak acid output (PAO) markedly increased from 43% on day 1 to 100% on day 5 during treatment with 20 mg p.o. The first 40-mg i.v. dose produced a median inhibition of 98% of PAO already on day 1. After 5 days of dosing, the inhibition had increased to 100%. On the other hand, a 10-mg i.v. dose could essentially maintain the degree of PAO reduction reached after 5 days of oral treatment. Plasma omeprazole concentrations increased during repeated dosing both with 20 mg p.o. and 40 mg i.v. PMID- 1291406 TI - Role of endogenously released cholecystokinin in determining postprandial insulin levels in man: effects of loxiglumide, a specific cholecystokinin receptor antagonist. AB - To estimate the contribution of postprandial cholecystokinin (CCK) responses to circulating insulin concentrations and insulin secretion, a specific CCK receptor antagonist (loxiglumide; 10 mg/kg body weight/h) or saline were infused intravenously in normal volunteers, beginning 90 min before insulin secretion was stimulated on separate occasions by the intraduodenal administrations of glucose, glucose and protein, and glucose plus protein with the admixture of pancreatin. The release of CCK (radioimmunoassay) was stimulated by the protein component of the nutrients from basal 2.4 +/- 0.4 to 8.0 +/- 1.2 pmol/l. CCK plasma levels were significantly higher with loxiglumide (p < 0.05). Glucose-dependent insulinotropic polypeptide (GIP) was also released by all nutrient mixtures. Loxiglumide significantly inhibited the amount of bilirubin and pancreatic enzymes recovered from duodenal aspirates. In contrast, in none of the experiments, C-peptide increments and hence insulin secretion rates were altered by loxiglumide. With glucose and protein as intraduodenal stimulus (no pancreatin added), the plasma amino acids rose significantly less (by approximately 50% of the control experiment) and the increment in insulin (but not C-peptide) concentrations was significantly reduced by loxiglumide. This is most likely explained by a change in insulin metabolic clearance. This effect cannot be a primary action of CCK because there was no similar effect of loxiglumide with the same intraduodenal stimulus plus added pancreatin. Pancreatic enzymes reduced maldigestion secondary to loxiglumide effects on pancreatic exocrine secretion: The increment in circulating amino acid concentrations was similar with and without loxiglumide. In conclusion, CCK does not alter insulin secretion and, therefore, is not an incretin hormone in man. Blocking CCK actions on the exocrine pancreas by loxiglumide, however, can secondarily cause reductions in postprandial insulin profiles by altering insulin clearance. These changes are possibly related to reductions in circulating amino acid concentrations. PMID- 1291407 TI - [Risks of contraception and pregnancy in patients with congenital cardiopathies. Retrospective study on 108 patients]. AB - 108 women with congenital heart disease in child-bearing age (16-38 years, mean age 28) were followed up for a period of ten years. Possible complications of contraceptive methods, and incidence of full-term pregnancies, spontaneous abortions and cardiovascular complications during pregnancy and delivery, were considered. Half of these patients had a cyanotic congenital heart disease, 23 had left-to-right shunt mainly at atrial level, 18 had right and 14 left ventricular outflow tract obstruction. 60 women had previous surgical procedures for their congenital heart disease. 83% of the patients were in NYHA functional class I-II. No complications were found during oral contraceptive regimen during intrauterine device insertion with antibiotic prophylaxis, except for the development of pulmonary hypertension in one patient with an atrial septal defect. 146 pregnancies occurred, but only 89 were full-term. There was a high number of interrupted pregnancies, rarely for medical reasons. The incidence of spontaneous abortion was similar to that of normal population (18% versus 10 15%). Maternal cardiovascular complications were found in the 22% of the full term pregnancies, but were well controlled by medical treatment. In conclusion, good family planning and pregnancies are possible in most young females with congenital heart disease. In the absence of cyanosis and pulmonary hypertension, oral contraception does not carry any particular risk. With appropriate medical care intrauterine devices may be an alternative in high risk patients. In the presence of a good cardiac function, a normal full-term pregnancy with an healty baby is the rule. A cesarean section is seldom needed. PMID- 1291408 TI - [Ventricular stimulation triggered by esophageal atriogram: a new technique of temporary physiologic stimulation in the course of acute myocardial infarct complicated by atrioventricular block and low cardiac output]. AB - Advanced atrio-ventricular (AV) block during acute myocardial infarction (AMI) is considered a complicating dysrhythmia as the well as mechanism responsible for occurrence of life-threatening hemodynamic changes. Often, simple VVI pacing can result insufficient in improving the decreased cardiac output. VDD pacing, which preserves atrial contribution, should represent the most effective electrical approach; therefore, it requires intracavitary placement of 2 catheters. In 10 pts (6M, 4F, mean age of 63.8 +/- 6.6 years) with advanced AV block due to AMI (4 inferior, 6 anterior) and without sinus node dysfunction, we performed stable VDD stimulation (mean 16.6 +/- 20.6 hours) using only one catheter positioned in the right ventricle while the atrial impulse, filtered (50-70 Hz) and amplified through a special device, was derived from the esophagus. Such technique is rapid and reliable, avoiding problems associated with atrial sensing and catheterization. PMID- 1291409 TI - [Diltiazem in paroxysmal supraventricular tachycardia: electrocardiographic findings at termination]. AB - The effects of diltiazem hydrochloride (0.3 mg/kg i.v. over 2 min.) was studied by continuous electrocardiographic monitoring in 60 patients. Conversion to sinus rhythm was achieved in 55 patients (91%). Electrocardiographic findings were: undisturbed sinus rhythm in 20 patients; A-V junctional rhythm in 4 patients; complex ventricular arrhythmias (ventricular tachycardia or complex VPCs) in 19 patients. Patients with complex ventricular arrhythmias were matched against patients with normal sinus rhythm, with respect to the following parameters: age, sex, heart disease, tachycardia duration, tachycardia cycle length, sinus cycle length, pre- and post-infusion blood pressure. No differences between the two groups of patients were found. Ventricular arrhythmias occurring at the termination of supraventricular tachycardia are difficult to explain. Nevertheless, these arrhythmias are not associated with organic heart disease. They could be the expression of triggered activity. PMID- 1291410 TI - [Relationship of Doppler indexes of left ventricular filling and exertion tolerance]. AB - The aim of this study was to evaluate if Doppler indexes of left ventricular filling are related to exercise capacity. Since a correlation between left ventricular filling pattern and causal blood pressure has been recently reported along a wide range of pressure values, a group of subjects with blood pressure ranging from normal to severely elevated values was studied. Twenty-four subjects (11 normotensives, 13 mild to severe hypertensive patients) underwent an echo Doppler study and a maximal multistage cycloergometric exercise test. Since the cycloergometric test was limited by fatigue or dyspnea in all subjects, exercise duration was used as an effort tolerance index. Echocardiographic indexes of systolic function resulted normal in all subjects. Significant relationships with exercise duration were found for several indexes of left ventricular filling (A peak: r = -.743, p < .0001; A/E ratio: r = -.606, p < .005; early filling fraction: r = .639, p < .001). Exercise time was also significantly related to casual blood pressure, both systolic and diastolic. The relationships between transmitral blood flow and exercise capacity seem to indicate that an impairment of ventricular relaxation (as indicated by the progressive increase of atrial contribution) is associated with a decreased exercise tolerance, possibly because a progressively lower activation of Frank-Starling mechanism. Diastolic function thus seems to be able to affect exercise tolerance even in subjects with normal systolic function and blood pressure ranging from normal to severely elevated values. PMID- 1291411 TI - [Reconstructive surgery of pure mitral insufficiency. Operative results and follow-up in 128 patients]. AB - Short and long-term results of valve repair for pure mitral insufficiency are reported in 128 consecutive patients with a mean age of 49 years (range 4-75). The etiology of the mitral valve dysfunction was degenerative in 54% of the cases, rheumatic in 30%, ischemic in 9.5%, endocarditic in 6.5%. Preoperatively, 91% of the patients were in NYHA class II or III. The anatomic lesions and the mechanism of mitral regurgitation were identified preoperatively by transthoracic and/or transesophageal echocardiography. Cardiac catheterization was performed only in patients with multiple valvular dysfunction and/or with evidence of concomitant coronary artery disease. Mitral repair was performed according to the techniques proposed by Carpentier. Only one patient died in the hospital (operative mortality: 0.8%). By actuarial methods, 96% of the patients were alive 4 years postoperatively, and 84% were reoperation free. Freedom from reoperation was significantly higher in patients who received a prosthetic ring than in those who had other types of anuloplasty (96% vs 67%; p < 0.05). During the follow-up period no patient had thromboembolic episodes. Ninety-seven per cent of the 112 patients who survived the operation and were not reoperated were in NYHA class I or II. These results confirm the validity of reconstructive surgery in pure mitral insufficiency. The use of a prosthetic ring gives stability to the repair and improves long-term results. PMID- 1291412 TI - [Surgical pathology of the aortic valve: a morphologic study on 912 surgically excised valves]. AB - A consecutive series of 912 surgically excised aortic valves was evaluated by means of macroscopic and histologic study. Pure aortic stenosis was diagnosed in 203 patients (p.) (22.25%), pure incompetence in 125 (13.72%) and combined dysfunction in 584 (64.03%). The diseases affecting the valves were: a) chronic rheumatic disease (593 p., 65%); b) dystrophic calcifications (214 p., 23%); c) noninflammatory aortic root disease (NIARD) and/or myxomatous infiltration of aortic cusps, floppy aortic valve (FAV) (55 p., 6%) d) infective endocarditis (50 p., 5.5%). Males outnumbered females with a ratio ranging from 2.4 (dystrophic calcific disease) to 1.6 (infective endocarditis). The mean age ranged from 37 +/ 7.5 (NIARD) to 61.2 +/- 6.3 (dystrophic calcific disease). Chronic rheumatic disease was the most frequent cause of stenoincompetence (542 p., 91.4%) while isolated stenosis was prevalently due to dystrophic calcification (172 p., 80.4%). The diseases causing isolated aortic incompetence were (in order of frequency): a) NIARD and/or FAV (55 p., 44%); b) infective endocarditis (50 p., 40%); and c) rheumatic disease (30 p., 16%). The 55 patients with NIARD and or FAV were divided into 3 groups: a) 23 p. with aortic root dilatation and normal cusps; b) 20 p. with aortic root dilatation and FAV; c) 12 p. with FAV but undilated aortic root. Aortic regurgitation was caused by cusp derangement in rheumatic disease (shortening, retraction) and infective endocarditis (perforations, erosions). Cusps diastasis and prolapse were the cause of regurgitation in aortic root dilatation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291413 TI - [Follow-up of patients undergoing surgery for aortic dissection: evaluation with transesophageal echocardiography]. AB - BACKGROUND: Transesophageal echocardiography (TEE) is a useful means in the diagnosis of acute aortic dissection (AD), owing to its very high sensibility and specificity. In this study, TEE was performed to assess post-surgical evolution. PATIENTS: Between 1982 and 1991, 119 pts. were operated on in our institution for AD (De Bakey I and II type): 87 pts. underwent replacement of the ascending aorta with a composite tubular graft bearing a mechanical valve; 26 had a simple tubular graft and 6 had aortic reconstruction. Sixty-eight of 72 discharged pts. were followed for up to 9.5 years (mean 4.5 +/- 2.6). Nine years after surgery actuarial survival of discharged pts. was 75%. Seven pts. died after a mean period of 3.4 years from surgery: only one died from postoperative complication (dehiscence of proximal anastomosis), none for aortic rupture distal to the graft. TEE was performed in 32 of these pts. and in other two operated on elsewhere, after 4.4 +/- 2.7 years from surgery; before the operation, type I AD was diagnosed in 23 pts. and type II in 11 pts. RESULTS: In 10/11 pts. with type II AD the aortic arch and the descending aorta looked normal; in one patient a localized intimal flap was found up to the arch. The descending aorta diameter was somewhat higher than in normal subjects (25.2 +/- 2.8 vs 21.9 +/- 3.7 mm), but in only one case was it beyond 2DS (32 mm). In all type I pts. an intimal flap persisted distal to the graft, along the whole thoracic aorta. Within the false lumen a flow was detected by color-Doppler in 14/23 pts. (61%), and spontaneous echo-contrast was noted in 14 pts. (61%). A thrombus was observed in 7 pts. (30%) and it was generally localized; in only one case it was extensive with total obliteration of the false lumen. In 16 pts. (70%) communications between the two lumina were found. The descending aorta diameter ranged from 25 to 53 mm, and mean value was higher than in normal subjects (34.2 +/- 6.2 vs 21.9 +/- 3.7 mm). CONCLUSIONS: In most pts. with type II AD, surgery can be a definitive treatment, as the remaining aorta keeps to normal size and appearance. In type I AD, operation is only palliative, as the dissection persists: the false lumen is often perfused through one or more communications with the true lumen and seldom its obliteration is noted. The persistence of dissection does not necessarily seem to be an ominous finding, as the survival of the study population was high and no patient died from aortic rupture. Nevertheless, long term prognosis can be affected by aorta dilation that often (but not always) follows the persistence of wall dissection. For its high reliability, easy feasibility and low cost TEE is a very useful method for following up patients operated on for AD and for detecting those who are at higher risk of aortic rupture because of lumen dilation. PMID- 1291414 TI - [Clinical significance of blood pressure response to posture]. AB - To assess the clinical significance of the blood pressure reaction to orthostatic posture, 55 normotensives and 369 subjects with different degrees of hypertension were studied with non-invasive 24-hour blood pressure monitoring. During the recordings blood pressure response to standing was evaluated at 8 a.m., and at 2, 4 and 7 p.m. All subjects were attributed a target organ damage score on the basis of ECG, chest x-ray and fundoscopic findings. To assess whether the orthostatic reaction may represent a marker for the severity of hypertension, subjects were divided into 4 classes of increasing blood pressure levels, and each class was further subdivided into two groups of subjects with orthostatic reaction above and below the mean value. On average, blood pressure rose by 2.7 +/- 9/7.2 +/- 7 mmHg while standing up, an increase which was inversely correlated to that of heart rate (p < 0.05). The orthostatic response was substantially constant throughout daytime hours. The systolic orthostatic change from lying to standing was directly correlated with age (p < 0.02) and average daytime blood pressure (p < 0.01), and inversely correlated with lying blood pressure immediately before standing up (p < 0.001). Both systolic (p < 0.05) and diastolic (p < 0.01) pressure responses to standing were related to the day-night blood pressure difference and to the standard deviation from mean daytime blood pressure. The degree of target organ damage was not significantly greater in the 4 groups of subjects with high orthostatic response compared to those with low response. The present results show that the pressure reaction to orthostatic stress is constant throughout daytime, even though a large intraindividual variability in the extent of the response is present. Orthostatic pressure change seems to be an important determinant of diurnal pressure rhythm, while it is not a marker for the severity of hypertension. PMID- 1291415 TI - [Validity of the proximal isovelocity surface area color Doppler method for calculating the valve area in patients with mitral stenosis; comparison with the two-dimensional echocardiographic method]. AB - BACKGROUND: The proximal isovelocity surface area (PISA) method, assessed by color Doppler echocardiography, has gained acceptance as a means of calculating flow rate through regurgitant orifice. The method can also be used to derive mitral valve area (MVA), by continuity equation, in patients with mitral stenosis (MS). The aim of this study was to compare the PISA method with the two dimensional echocardiographic planimetry (2D) method and pressure half-time method (PHT) in MVA calculations in a group of 37 patients with MS. METHODS AND RESULTS: All of these patients had satisfactory MVA by 2D method. There were 22 female and 15 male; age 56 +/- 11 years (range 32-71); 19 were in sinus rhythm (SR) and 18 in atrial fibrillation (AF); 17 patients had pure MS, while the remaining 20 had associated mitral regurgitation (MR); in 23 patients the orifice morphology was circular or elliptic, and was defined as regular; while in 14 patients the morphology was irregular for the presence of two or more nodular calcifications on the commissures or leaflet's edges. MVA by PISA method was calculated assuming a uniform radial flow convergence region along a hemispherical surface, according to the formula: MVA = 2 pi r2 Vn(1-cos theta)/Vmax; where r was the PISA radius measured in 2D from the first alias to the mitral leaflet's edge; Vn was the flow velocity at radial distance from the mitral orifice; Vmax was the peak transmitral velocity by CW Doppler; 1-cos theta was a factor that accounted for the inflow angle formed by the mitral leaflets. The Nyquist limit was lowered to 29 cm/sec. Alpha angle formed by the mitral leaflets ranged between 86 degrees and 134 degrees; average 110 degrees +/- 10 degrees. 2D MVA was 1.33 +/- 0.37 cm2; range 0.69-2.2 cm2; PHT MVA was 1.29 +/- 0.34 cm2; range 0.70-2.1 cm2; PISA MVA was 1.18 +/- 0.36 cm2; range 0.47-1.95 cm2. The PISA method underestimates MVA by 0.15 +/- 0.21 cm2, in comparison with the 2D method; and by 0.11 +/- 0.18 cm2 in comparison with PHT method (p ns). The correlation between 2D and PISA MVA was: r = 0.84; p < 0.001; y = 0.83x + 0.06; 95% confidence intervals +/- 0.40 cm2; and between PHT and PISA MVA was: r = 0.79; y = 0.84x + 0.09; p < 0.001; 95% confidence intervals +/- 0.46 cm2. The correlation coefficient was similarly good in patients with SR or AF, and did not significantly change in patients with pure MS or MS+MR; neither did it vary with respect to the orifice morphology (p < 0.001 for all the variables considered), except for the correlation PHT-PISA in the group of patients with irregular orifice morphology (r = 0.70; p = 0.005). The interobserver and intraobserver variability were, respectively: 2.2% and 4.4% for 2D MVA; 3.4% and 3.8% for PHT MVA; 5.2% and 3.5% for the PISA radius; 6.1% and 4.4% for the alpha angle; 10.2% and 7.2% for PISA MVA (F ratio of variances ns). CONCLUSIONS: In conclusion, the PISA method allows accurate assessment of MVA in patients with MS, regardless of cardiac rhythm or additional MR. Moreover, our study suggests that orifice morphology does not affect the accuracy of this method. PMID- 1291416 TI - [Role of transtoracic and transesophageal echocardiography in guiding the reparative surgery of the myxomatous mitral valve and its follow-up]. PMID- 1291417 TI - [Involvement of the heart valves and great vessels in homozygote familial hypercholesterolemia]. AB - Homozygous familial hypercholesterolaemia is characterized by cutaneous xanthoma development from infancy, precocious and accelerated atherosclerosis with clinical signs of ischemic heart disease and frequent involvement of left heart valves resulting in stenosis and/or incompetence. Two cases are described of this condition, both associated with aortic stenosis. In one case mitral incompetence and thromboembolic pulmonary hypertension were also found. The mitral valve is involved in the atherosclerotic process at the level of the cusps. These become thickened and stiff. Aortic stenosis is mainly due to atheromas infiltrating the Valsalva sinuses and the ascending aorta. Pulmonary hypertension, never reported before in this disease, is probably due to concomitant atheromatosis involving the pulmonary artery with secondary fatty embolism. PMID- 1291418 TI - [Debate on chronic cardiopathy]. PMID- 1291419 TI - [Aspirin in acute myocardial infarct]. PMID- 1291420 TI - [Age-induced changes in the cardiovascular system in normal subjects]. AB - To assess the effect of age on cardiac structure and function, we performed echocardiograms on 104 physically active, normal, community-dwelling volunteers (68 men and 36 women), ranging in age from 18 to 84 years and having no evidence of hypertension or cardiovascular disease. With advancing adult aging, the following were observed: a decrease in aortic compliance (r = 0.42); an increase in systolic (r = 0.61), diastolic (r = 0.24), pulse (r = 0.60) and mean (r = 0.48) arterial pressure; and a modest enlargement of aortic root (r = 0.47) and left atrial dimension (r = 0.30) were observed. Left ventricular end-diastolic volume (r = 0.25), wall thickness (r = 0.30) and mass (r = 0.37) also increased with aging, while left ventricular end-systolic volume was not age-related. Furthermore, a stepwise multivariate linear model identified the decrease in arterial compliance (R2 = 0.06; p < 0.02) and the increase in left ventricular stroke work (R2 = 0.38; p < 0.0001) as the only variables independently related to the increase in left ventricular mass that occurs with advancing age. Regarding left ventricular systolic function, aging was also related to an increase in left ventricular stroke work (r = 0.40) and ejection time (r = 0.44), while pump function, (measured as ejection fraction and cardiac index at rest), and contractility (measured by load independent end-systolic indexes) were unaffected by aging. Conversely, pulsed Doppler analysis of mitral inflow showed a significant age-related decline in the peak early filling velocity (r = -0.45) and in the ratio of early and late diastolic filling velocity (r = -0.66), while peak late diastolic flow velocity (r = 0.50), diastolic pressure half time (r = 0.34) and duration of isovolumic relaxation (r = 0.56) increased significantly with age. PMID- 1291421 TI - [Prognostic value of the dipyridamole-echocardiography test immediately after a non-complicated myocardial infarct: a large scale multicenter study. Echo Persantine Italian Cooperative Study]. AB - BACKGROUND: Any new diagnostic test should follow a pathway similar to that of a new drug, from initial studies in highly selected populations under strictly controlled conditions, up to large scale multicenter trials more likely to represent the true performance of the test in the clinical arena. AIM OF THE STUDY: To evaluate the capability of prognostic stratification of high dose (up to 0.84 mg/kg over 10') dipyridamole-echocardiography test (DET) early after an acute myocardial infarction in a "phase IV" study, based upon 11 different echocardiographic laboratories, all with established experience in stress echo and fulfilling quality control requirements for stress echo readings. STUDY POPULATION: Nine-hundred twenty five patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS: During DET, one major adverse reaction occurred, consisting of a prolonged ischemia resistant to aminophylline and nitrates, and progressing to small uncomplicated reinfarction. In 11 patients the lower dipyridamole dose (0.56 mg/kg over 4') gave limiting side effects. Patients were followed up for 14 +/- 9.9 months (range = 1.53). During the follow-up, there were 34 deaths and 37 non-fatal myocardial infarctions; 104 patients developed class III or IV angina, and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction and death), the most important univariate predictor was the result of DET (chi-square = 45.8). With a Cox analysis, echocardiographic positivity, age and sex were found to have an independent and additive value. Considering survival (and therefore death as the only event) age was the most meaningful parameter, followed by the Wall Motion Score Index during dipyridamole (chi-square = 12.1); among other parameters, the resting Wall Motion Score Index was a significant predictor of death. By Cox analysis, age (relative risk estimate = 1.02) and Wall Motion Score Index during dipyridamole (relative risk estimate = 14) showed an independent and additional prognostic value. In particular, considering death only, the event rate was of 2% in patients with negative DET, 4% in patients with high dose positive DET and 7% in patients with low dose positive DET. CONCLUSIONS: Dipyridamole echocardiography is feasible and safe early after uncomplicated myocardial infarction and allows an effective risk stratification on the basis of the presence, severity, extent and timing of the induced dyssynergy. In particular, the risk of death doubles in patients with high dose positivity and almost quadruples in patients with low dose positivity. PMID- 1291422 TI - [Long-term treatment of stable angina pectoris with gallopamil]. AB - BACKGROUND: The effects of long-term treatment with gallopamil 50 mg t.i.d were assessed in 8 patients, 7 males and 1 female, aged 47-69 years, with stable angina pectoris, positive exercise tests, coronary artery disease and no previous myocardial infarction. METHODS: Clinical and ECG parameters as well as exercise testing, 24-hour Holter and echocardiography were assessed before treatment, after 3 months, after 1 and 2 years of treatment, and following final wash-out. RESULTS: Comparing each treatment period to baseline, a significant decrease in resting heart rate (from 66 +/- 9 beats/min at baseline to 56 +/- 7 beats/min after 3 months [p < 0.01], 59 +/- 8 beats/min after 1 year [p < 0.05] and 58 +/- 9 beats/min after 2 years [p < 0.05]), systolic (from 162 +/- 19 mmHg at baseline to 147 +/- 12 mmHg after 3 months [p < 0.05], 146 +/- 20 mmHg after 1 year [p < 0.01] and 146 +/- 27 mmHg after 2 years [p < 0.05]), and diastolic (from 89 +/- 6 mmHg to 82 +/- 7 after 3 months [p < 0.05], 82 +/- 4 after 1 year [p < 0.05] and 83 +/- 4 after 2 years [p < 0.05]) blood pressure was observed. Exercise time significantly improved (from 596 +/- 209 seconds to 802 +/- 66 seconds after 3 months [p < 0.01], 710 +/- 167 seconds after 1 year [p < 0.05] and 723 +/- 125 seconds after 2 year [p < 0.05]), while heart rate and rate-pressure product at peak exercise did not change. The number of ischemic episodes and the total ischemic time per 24 hours significantly decreased (from 35 +/- 15 min to 12 +/- 10 min after 3 months [p < 0.05], 10 +/- 8 min after 1 year [p < 0.05] and 11 +/- 9 min after 2 years [p < 0.05]). Ejection fraction increased (from 66 +/- 10% to 77 +/- 7% after 3 months [p < 0.01], 80 +/- 5% after 1 year [p < 0.01] and 80 +/- 3% after 2 years [p < 0.01]), while contractility, as expressed by the end systolic stress/end systolic volume ratio remained unchanged. No serious side effects or biochemical abnormalities developed. CONCLUSIONS: Gallopamil appears to be safe, well tolerated and effective in the long term control of angina pectoris; its effects are fully developed at 3 months and persist unchanged after 2 years. For its hypotensive action and the lack of significant effects on myocardial contractility, gallopamil appears to be potentially useful in patients with associated angina and hypertension and in patients with impaired left ventricular function. PMID- 1291423 TI - [Lipid parameters and cardiovascular risks in elderly patients hospitalized for ischemic cardiopathy. A case-control study]. AB - In order to evaluate whether and to what extent elevated blood lipid concentrations and clinical expressions of coronary heart disease (CHD) are associated in the elderly, we studied the risk of CHD (myocardial infarction and angina pectoris) in a population of elderly hospitalized patients (210 subjects, 126 men and 84 women, average age 76 +/- 6 years) exposed to risk factors. 210 patients, free from current and previous cardiovascular diseases, age and sex matched, were recruited as the control group. Advanced senile decline, severe hepatic or renal failure and malignancies were considered exclusion criteria for both groups. The following dichotomic variables (familial history of CHD, cigarette smoking, clinical history of arterial hypertension or diabetes mellitus, hypercholesterolemia, hypertriglyceridemia) and continuous variables (total, LDL and HDL cholesterol, triglycerides, total/HDL cholesterol ratio, body mass index (BMI), years of exposure to risk factors) were considered. Using a stepwise multiple logistic regression forward method, the following variables resulted significantly associated with the risk of CHD: total/HDL cholesterol ratio (OR 1,89), BMI (OR 1,04), period of hypertension (OR 1,04) and cigarette smoke exposure (OR 1,007). We conclude that in the elderly the total/HDL cholesterol ratio can be a more predictive and reliable index of coronary risk than blood total cholesterol concentration. PMID- 1291424 TI - [Management and prognosis of acute myocardial infarct in advanced age: comparison of the cardiac intensive care unit and the cardiology ward]. AB - The aim of this prospective study was to assess the prognostic and most suitable management of AMI in elderly patients (age > or = 75 years). From September 1988 to August 1991, 129 such patients (pts) were evaluated: 35 (27%) were admitted to CCU because of arrhythmias or severe hemodynamic complications; 94 (73%) were addressed, according to bed availability, to CCU (55 pts) or Cardiology Ward (39 pts), where all patients underwent continuous ECG monitoring for at least 72 hours. Age, gender, history of previous angina or myocardial infarction, presence of chest pain or ECG ischemia on admission, site and extent of AMI, delay on admission, CPK-MB peak, recurrent angina, arrhythmias, heart failure, emotional disorders, hospital mortality and length of hospital stay were compared. Our results show that elderly patients who suffered from complicated AMI were at high risk for death and severe in-hospital complications. No significant prognostic differences were observed between the two groups with uncomplicated AMI. Thus hospitalization in the Cardiology Ward seems to be valuable, safe and well tolerated in our population of elderly patients with AMI, and without initial complications. PMID- 1291425 TI - [Clinical and prognostic significance of echocardiographic parameters in dilated cardiomyopathy: a prospective study on 225 patients. The Italian Multicenter Study of Cardiomyopathies Group]. AB - To assess the prognostic role of echocardiographic indexes and their relation to clinical conditions, 225 patients with dilated cardiomyopathy were studied prospectively. All cases had a normal coronary angiogram and non specific endomyocardial biopsy findings. 163 men (72.4%) and 62 women (27.6%), mean age 41.5 +/- 12.3 (range 8-61), were studied. Clinical, electrocardiographic and echocardiographic parameters, normalized for body surface area, were tested according to NYHA class and presence of segmental or diffuse wall motion abnormalities. One hundred-four patients were in NYHA class I-IIa, 94 were in class IIb-III and 27 were in class IV. Left ventricular end systolic diameter index, right ventricular end diastolic diameter index, left atrial diameter index, left ventricular fractional shortening and ejection fraction, and radius to wall thickness ratio were significantly more impaired in patients with more severe symptoms. Twenty-eight patients (13%) showed segmental wall motion abnormalities and had smaller left ventricular end systolic and left atrial diameter index and higher left ventricular fractional shortening and ejection fraction. During a mean follow up of 23 +/- 15 months (range 1-67 months), 25 patients (11.1%) died from cardiac causes and 16 (7.1%) underwent heart transplant because of refractory heart failure. Prognostic evaluation was performed separately for cardiovascular mortality alone and for cardiac events (cardiovascular mortality and heart transplantation). At Cox multivariate analysis only right ventricular end diastolic diameter index (p < 0.005) predicted cardiovascular mortality, while left atrial diameter index (p < 0.001), right ventricular end diastolic diameter index (p < 0.01) and left ventricular ejection fraction (p < 0.05) were significant independent predictors of cardiac events. PMID- 1291426 TI - [Primary cardiac rhabdomyosarcoma involving the mitral valve]. AB - Primary cardiac rhabdomyosarcoma is rare and its extension to the mitral valve even rarer. We report a case of left atrial rhabdomyosarcoma involving the mitral valve. The patient was a 62-year-old man who complained of recurrent pre-syncopal episodes, dyspnoea often sudden in onset, asthenia and major weight loss (10 kg in one month). 2-D echocardiography revealed a 4.9 cm2 wide mass attached to the atrial side of the anterior mitral leaflet and to the adjacent inferior interatrial septum, where it seemed to have origin. CT scan and scintigraphy revealed bone, kidney and spleen metastases. The patient underwent emergency cardiac surgery because of increasing pre-syncopal and dyspnoeic episodes due to obstruction by the intracardiac mass. At surgery a tumor was found infiltrating the left atrial wall, the interatrial septum, the mitral anulus and the anterior mitral leaflet up to its tip. Invasion of mitral anulus did not allow mitral valve replacement, so that an excision of the intracardiac mass was performed as extensively as possible. Histology revealed a rhabdomyosarcoma. A post-operative chemotherapy cycle had to be stopped due to onset of atrial fibrillation and dyspnoea. 2-D echo monitoring revealed rapid new growth of the tumor across the basal portion of mitral valve leaflet to the atrioventricular orifice. After several episodes of increasing dyspnoea, the patient had a pulmonary oedema and died. PMID- 1291427 TI - [Guidelines for the use of the implantable defibrillator. Combined task force of the Italian Group of Arrhythmia and the Italian Association of Cardiostimulation]. PMID- 1291428 TI - [Congresses and ethical problems]. PMID- 1291429 TI - Diminished autonomy: can a person with dementia consent to dental treatment? PMID- 1291430 TI - The top of 20 prescribed medications in 1991. PMID- 1291431 TI - Developing an effective occupational exposure policy for the dental office. PMID- 1291432 TI - Diagnosis, treatment, and prevention of incomplete tooth fractures. PMID- 1291433 TI - Effective methods for drying root canals. PMID- 1291434 TI - An inexpensive method of drying etched enamel tooth surface. PMID- 1291435 TI - Soft-tissue management through effective patient subgingival bacterial control. PMID- 1291436 TI - Economic trends in dentistry, 1974-1990. PMID- 1291437 TI - Ethics and its role in dentistry. PMID- 1291438 TI - A new surgical needle for periodontology. PMID- 1291439 TI - Microleakage in amalgam restorations following burnishing, polishing, and time varied thermocycling. PMID- 1291440 TI - Unilateral bifid mandibular condyle. PMID- 1291441 TI - Galvanic action. PMID- 1291442 TI - Severe odontogenic infection associated with disseminated intravascular coagulation. PMID- 1291443 TI - Autogenous transplant involving a supernumerary tooth. PMID- 1291444 TI - Calcium-binding proteins: basic concepts and clinical implications. AB - Calcium ions exert their effects in part via interactions with a wide variety of intracellular calcium-binding proteins. One class of these proteins shares a common calcium-binding motif, the EF-hand. A consensus amino acid sequence for this motif has aided the identification of new members of this family of EF-hand proteins, which now has over 200 members. A few of these proteins are present in all cells, whereas the vast majority are expressed in a tissue-specific fashion. The physiological function of a few of these proteins is known to be achieved via a calcium-dependent interaction with other proteins, thereby regulating their activity. Some members, like parvalbumin, calbindin, and calretinin, proved to be useful neuronal markers for a variety of functional brain systems and their circuitries. Their major role is assumed to be buffering, transport of Ca2+, and regulation of various enzyme systems. Since cellular degeneration is accompanied by impaired Ca2+ homeostasis, a protective role for Ca(2+)-binding proteins in certain neuron populations has been postulated. Another protein family are the annexins, members of which interact with phospholipids and cellular membranes in a calcium-dependent manner. In some cases members of the annexin family were even found to interact with EF-hand proteins. Certain annexins have been suggested to be involved in anti-inflammatory response, inhibition of blood coagulation, membrane trafficking or cytoskeletal organization, but several of these functions have been questioned recently. The elucidation of the interactions and functions of the majority of these proteins remains a challenging task for the coming years. PMID- 1291445 TI - Distribution of calcium during contraction and relaxation of crayfish skeletal muscle fibre. AB - A model of activation of muscle contraction has been applied to the crayfish isolated skeletal muscle fibre. The model is based on calcium diffusion and binding to specific regulatory sites in a sarcomere. Calcium ions activate interactions of contractile proteins and thus the generation of force. The model quantifies the relation between calcium released from intracellular stores and force elicited. Experimental tension records from isolated crayfish skeletal muscle fibres under voltage clamp conditions are analyzed. Model parameters were determined either via approximation of the onset of tension by the model solution or from the model based relations between the tension maximum, and depolarizing pulse length and amplitude. This allowed to determine time changes of free and bound calcium distribution in the sarcomere and the calcium release from terminal cisternae. The steady state calcium concentration at terminal cisternae showed S shaped voltage dependence with saturation below approx. 10 mumol/l at positive membrane potentials. PMID- 1291446 TI - Comparison of 9-aminoacridine and atebrine induced changes in optical, electrical and mechanical characteristics of lipid bilayers. AB - The effects of fluorescent probes 9-aminoacridine (9AA) and atebrine (AT) on physical properties of liposomes and planar bilayer lipid membranes (BLM) were studied. The method of fluorescence spectroscopy and the electrostriction method based on measurement of higher current harmonics were used. At low concentrations (10(-5)-5 x 10(-5) mol/l), 9AA increased fluorescence intensity, while in liposomes from soybean phosphatidylcholine fluorescence quenching occurred at higher probe concentration. Fluorescence quenching occurred over the entire concentration range tested (10(-5)-10(-4) mol/l) in liposomes made from a mixture of egg phosphatidylcholine and cardiolipin. In contrast to 9AA, AT, thanks to its hydrophobic chain, penetrates deeper into the hydrophobic membrane moiety; thus, immobilization of the molecule and an increase in fluorescence intensity was always observed. Probes adsorbed to membranes, leaving their electric capacitance effectively unchanged. Adsorption of charged dye particles induced small changes in transmembrane potential. In the presence of 10(-5) mol/l AT, the modulus of elasticity E perpendicular increased somewhat for soft membranes (E perpendicular approximately 2.5 x 10(7) Pa), whereas it decreased for hard membranes (E perpendicular approximately 5 x 10(7) Pa). pH gradient present on the membrane affected the ability of the dyes to incorporate into the membranes. Our results provide evidence against the proposed model of the quenching mechanism introduced by Rottenberg and Lee (1975). PMID- 1291447 TI - Model of distribution of anticancer agents transplanted into the brain tissue using the random walk method. AB - A Monte-Carlo approach to analysis of dispersion in the tissue of a locally administered drug is presented. The distribution of a drug in the tissue is simulated as a distribution of randomly walking particles. The approach is demonstrated on a simple situation for which both experimental results and an analytical solution are known. The approach can be used in situations, where common numeric methods are difficult to use, especially for analyses of drug transport in an inhomogeneous space, and problems with complex boundary conditions, e.g. in analyses of dispersion of anticancer agents locally applied into tumours. PMID- 1291448 TI - The graviosmotic hypothesis of xylem transport of water in plants. AB - This paper presents a full version of the graviosmotic hypothesis postulated earlier in outline (Kargol 1978), which concerns xylem rise of water in plants. According to this hypothesis water is transported by xylem vessels (at respective development stages of these vessels) using the graviosmotic mechanisms. A detailed description of hypothesis is introduced by a discussion of the development stages of xylem vessels and a presentation of graviosmotic mechanisms postulated to be involved. These mechanisms include: convective graviosmosis and related effects, gravidiffusional graviosmosis, and osmotic transport aided by gravitational force in multi-membrane systems. The presented hypothesis does not contradict the theory of transpiration-cohesion or that of root pressure; rather, it is complementary to them. PMID- 1291450 TI - Critical cell volume and shape of bovine erythrocytes. AB - The relationship between erythrocyte shape and the critical cell volume was investigated. Agents able to increase the critical cell volume induced three main stable shapes of erythrocytes: discocytic, stomatocytic, and echinocytic. The absence of correlation between shape and critical cell volume under isoosmotic conditions suggests that relative differences between the surface areas of the inner and the outer leaflet of the cell membrane do not influence the critical volume of a cell. PMID- 1291449 TI - Comparison of cytochrome P-450- and peroxidase-mediated activations of carcinogenic azo dyes and N-nitrosamines. AB - Carcinogenic azo dyes (dimethylaminoazobenzene, Sudan I) and N-nitrosamines (N nitrosomethylaniline, N-nitrosomethylbenzylamine) are oxidized by cytochrome P 450 isoenzymes and peroxidase yielding metabolites which in vitro bind to DNA and transfer RNA (tRNA). The parallelism and differences in oxidative reactions are described. Peroxidase is more effective than P-450 in activating reactions of some carcinogens studied. The presence of either of these enzymes is supposed to be responsible for the organ and/or cell type specific effects of the carcinogens studied. PMID- 1291451 TI - Potassium channel blockers from Ruta--a new approach for the treatment of multiple sclerosis. PMID- 1291452 TI - A scanning electron microscope study of Toxocara genettae Warren, 1972 (Ascaridae), with data on morphometric variation. AB - We have carried out a morphometric study of the ascaridoid nematode Toxocara genettae, parasite of the small intestine of the genet Genetta genetta, with the aid of scanning electron microscopy (SEM). Host specimens were trapped in Galicia, NW Spain. The most characteristic features of this nematode are the absence of cervical alae, replaced by narrow lateral crests running along the length of the body and the presence of a mucron at the end of the male tail. Other features of interest include the number of labial denticles (90-98 and 96 102 on the dorsal lip, 82-96 and 90-96 on the subventral lip of male and female, respectively), the width of the transverse striations (25-28 microns) and, in many of the specimens examined, the position of the precloacal median papilla at the base of a well-defined cuticular pit. PMID- 1291453 TI - Immunization of rabbits with antigens from Psoroptes cuniculi, the rabbit scab mite. AB - Rabbits immunized with the whole body extract of Psoroptes cuniculi (Delafond, 1859) developed partial immunity to the infestation with this mite. These rabbits manifested P. cuniculi antigen-induced cell response and a high level of specific serum antibody after the immunization. Electrophoretic separation of the mite extract followed by immunostaining with various sera revealed differences between artificially immunized and naturally infested rabbits to most of the P. cuniculi antigens. However, the specific antibody pattern, that was developed by the immunized rabbits, was not changed after these rabbits were infested with the mites. PMID- 1291454 TI - An experimental transmission of porcine strains of Blastocystis sp. in the laboratory mice and gerbils. AB - Outbred laboratory mice were successfully infected with porcine strains of Blastocystis sp. using faecal stages as well as stages from fresh or passaged cultures. In contrast, inbred BALB/c mice and gerbils were only rarely infected and the intensity of their infection was mostly negligible. Blastocystis sp. was never observed inside the host cells. These results indicate a low host specificity of Blastocystis sp. as well as different sensitivity of investigated hosts to Blastocystis sp. infection. PMID- 1291455 TI - Inhibition of proliferation of tumour cell cultures by biologically active substances isolated from the tissues of Fasciola hepatica and Fasciola hepatica infected rat liver. AB - Biologically active substances (BAS) were isolated from the tissues of Fasciola hepatica L. and from F. hepatica-infected rat liver by ethanol precipitation from aqueous tissue homogenates. A marked inhibiting effect of the newly isolated BAS on hepatoma MC29 cell culture proliferation and a slight inhibiting effect of the newly isolated BAS on myeloma cell culture proliferation was found. The strongest inhibiting effect was by BAS isolated from the tissues of F. hepatica. The inhibiting effect of the BAS isolated from F. hepatica-infected liver was stronger than the effect of the BAS isolated from normal liver tissue. PMID- 1291456 TI - Gyrodactylus bohemicus sp. n. (Monogenea: Gyrodactylidae) from Oncorhynchus mykiss (Walbaum) and Salvelinus fontinalis (Mitchill) (Clupeiformes: Salmonidae) in Czechoslovakia. AB - Gyrodactylus bohemicus sp. n (Gyrodactylidae: Monogenea) is described from the fins, skin and gill filaments of Oncorhynchus mykiss (Walbaum) and Salvelinus fontinalis (Mitchill) (Clupeiformes: Salmonidae) from a trout farm in Czechoslovakia. G. bohemicus sp. n. is most closely related to G. thymalli Zitnan, 1960 and G. magnus Konovalov, 1967 in the shape of the anchors, the ventral and the dorsal bar, but can be distinguished from both these species by the shape of the marginal hook proper. PMID- 1291457 TI - Cercariae of Trichobilharzia szidati Neuhaus, 1952 (Trematoda: Schistosomatidae): the causative agent of cercarial dermatitis in Bohemia and Moravia. PMID- 1291458 TI - Childhood diarrhoea due to rotavirus in a community. AB - The etiologic role of rotavirus in acute diarrhoeal illness in children under five years of age was studied over a period of one year in an urban slum community. Rotavirus was detected in 17.7 per cent of 376 children with diarrhoea and 4 per cent of 299 healthy children with maximum prevalence at 19-24 months of age with statistically comparable detection in 0-6 months of age. The overall prevalence was significantly higher in children below 2 yr as compared to those between 2-5 yr of age. Girls (24.1%) were more susceptible amongst the diarrhoeal group in comparison to boys (13.8%). Diarrhoea due to rotavirus was more prevalent during the cooler months (November-February) of the year and no correlation was observed with rainfall and relative humidity. Rotavirus as the sole pathogen was observed in 9 per cent children with diarrhoea and in the rest, association of Cryptosporidium (3%) was observed for the first time with this virus along with other known enteropathogenic bacteria and parasites, enterotoxigenic Escherichia coli being the commonest organism. PMID- 1291459 TI - Viability of acid-fast bacilli from gamma-& UV-irradiated lepromatous armadillo tissues infected with Mycobacterium leprae. AB - Gamma-irradiated splenic homogenates of armadillos infected with M. leprae proved sterile by conventional tests and media. However, on media for chemoautotrophy, these could repeatedly grow as a single type of acid-fast nocardioform bacterium like the unirradiated specimens, although with a much reduced count. In the slide culture, transition from the initial AFB/coccoid bodies, to sporulating mycelia and granules in the final stage, could be observed sequentially. The gamma irradiated tissue specimens failed to yield any other mycobacterium/corynebacterium tested according to standard protocols. PMID- 1291460 TI - Poor diagnostic value of adenosine deaminase in pleural, peritoneal & cerebrospinal fluids in tuberculosis. AB - Adenosine deaminase (ADA) was estimated in 84 pleural, 140 peritoneal and 136 cerebrospinal fluids to study its diagnostic usefulness as a routine test for tuberculosis. The sensitivity, specificity, positive and negative predictive values for diagnosing tuberculosis in pleural fluids (ADA > 30 U/l) was 67, 92, 78 and 87 per cent respectively, in peritoneal fluids (ADA > 15 U/1) it was 89, 81, 25 and 99 per cent respectively and in cerebrospinal fluids (ADA > 10 U/l) it was 50, 90 21 and 97 per cent respectively. The differences in mean ADA levels between tuberculous (28.0 and 19.5 U/1) and non-tuberculous (9.7 and 4.8 U/1) peritoneal and cerebrospinal fluids although statistically significant (P < 0.001), were of no practical clinical value. A wide scatter in ADA values was seen in both tuberculous and non-tuberculous fluids. ADA estimation in plasma, lymphocytes and cell fractions of fluids was also not diagnostically useful nor did it throw light on the source of elevated ADA in fluids. PMID- 1291461 TI - Intestinal colonization & production of diarrhoea by enteroadherent-aggregative Escherichia coli. AB - The ability of HEp-2 cell adherent Esch. coli of aggregative phenotype (EA-Agg EC) to cause diarrhoea and to colonize the bowel of rabbits was studied. Thirty six rabbits were challenged with one of three EA-Agg EC strains (F23A; H766C and F17A-15, 3 and 3 rabbits respectively) or a control strain (K12-15 rabbits) in reversible ileal-tie in adult rabbit diarrhoea (RITARD) model. The animals were sacrificed 72 h post challenge. Severe diarrhoea occurred in greater number of F23A challenged rabbits than the controls (P < 0.05). Mucosal cultures from proximal and distal small intestine and colon yielded about 1000 times more Esch. coli in the test than control rabbits (P < 0.001 in each case). EA-Agg EC were consistently grown from mucosa in the test rabbits who commonly showed mild to moderate villous stunting and grade + to nuclear fragmentation (karyorrhexis) in the small and large bowel epithelium. The control animals had either normal villi or very mild villous stunting. Results comparable to F23A were obtained with the other two EA-Agg EC strains tested in a smaller number of animals. PMID- 1291462 TI - Loss of some virulence factors of enterotoxigenic Escherichia coli on repeated subcultures. AB - Thirty enterotoxigenic Esch. coli (ETEC) strains of predominant serogroups, isolated from patients with diarrhoea in Ludhiana, Punjab were investigated for expression of heat labile (LT) enterotoxin and colonization factor antigens (CFAs) on repeated subculture. These belonged to serogroup 078 (10), 080 (2), 0114 (6), 020 (3), 0128 (3), 0153 (2) and 08 (4) respectively. The isolates exhibited a differential response for expression of LT and CFAs on repeated subculturing. All the strains were positive for both LT and CFA up to six subcultures. Three strains of serogroup 0114 and one of 080 failed to express CFA while one strain each of serogroups 080, 0114, 020 and 08 failed to elaborate LT in the 8th subculture. Only 25 and 19 isolates were detected as stable producer of LT and CFAs up to 10th subculture. PMID- 1291463 TI - Effect of Vibrio cholerae-L-asparaginase on surface structure of splenic lymphocytes. AB - The surface ultrastructure of splenic lymphocytes and rosetting properties of lymphocytes of Swiss mice were studied under scanning electron microscope following transplantation of Dalton's lymphoma and ascites fibrosarcoma tumour cells and administration of Vibrio cholerae-L-asparaginase. The results were compared to those obtained with the standard Escherichia coli-L-asparaginase. The surface structure of the lymphocytes (T cells) following L-asparaginase administration was not so different from that of normal lymphocytes. V. cholerae L-asparaginase did not cause higher number of rosette formation in T cells as compared to the normal group. The study thus revealed that V. cholerae-L asparaginase did not have a significant stimulatory or non-immunosuppressive effect on the lymphocyte functions. PMID- 1291464 TI - Role of iron in the virulence of Vibrio vulnificus isolated from Cuddalore coastal waters (India). AB - V. vulnificus strains isolated from different sources of Cuddalore coastal waters were tested for their virulence activity through their LD50 values in mice. As infections of V. vulnificus have been correlated with pre-existing liver disease and hemochromatosis, the role of iron on virulence was determined using. iron overloaded mice. The LD50 was in the range of 10(4)-10(7) cells in normal mice but 10(1)-10(2) cells in iron-injected mice, thus providing evidence that iron may play a major role in the pathogenesis of V. vulnificus. PMID- 1291465 TI - Biting rhythm & biting activity of phlebotomid sandflies. AB - The biting behaviour of Phlebotomid sandflies was studied in a rural village of Pondicherry through all night collections for a period of one year, using human volunteers and cattle as baits. Phlebotomus papatasi was caught only on human bait, showing anthropophily while Ph. argentipes was caught on cattle baits, showing zoophily. The biting activity was seen throughout the night, reaching a peak of 0100 h in Ph. papatasi and 0200 h in Ph. argentipes. PMID- 1291466 TI - Electromagnetism in medicine. PMID- 1291467 TI - Clinical significance of kidney biopsy in acute renal failure (ARF). AB - Out of 152 cases of Acute renal failure (ARF) 32 patients (21%) were subjected to kidney biopsy. All patients had intrinsic ARF. Prerenal azotemia and obstructive uropathy were excluded. Histologic observations were: Crescentric glomerulonephritis in 7 (21.9%), acute endocapillary proliferative glomerulonephritis 5 (15.6%), acute interstitial nephritis 7 (21.9%), necrotizing vasculitis 4 (12.5%), acute tubular necrosis in 5 (15.6%) and membrano proliferative GN with superimposed crescent in 2 (6.2%) while renal cortical necrosis was seen in 6.2% of cases. Prebiopsy diagnosis was correct in only 10 (31.25%) cases. The result of biopsy had altered clinical diagnosis in 22 (68.75%) patients and precise renal biopsy diagnosis resulted in therapeutic changes in 54.8% of patients with ARF. PMID- 1291468 TI - Evaluation of Ehrlich's test as screening test for cancer. AB - Ehrlich's test, serum mucoproproteins, phosphohexoisomerase (PHI), and lactate dehydrogenase (LDH) levels were studied in patients with cancer and age matched controls. All parameters studied were found to be significantly increased in cancer. Evaluation of Ehrlich's test, PHI and LDH for their validity as screening tests revealed that Ehrlich's test is better suited as a screening test for cancer. A positive correlation observed in the study between serum mucoproteins and Ehrlich's test strengthens the postulation that mucoproteins are responsible for the colour development in Ehrlich's test. PMID- 1291469 TI - Colonic emergencies in geriatric practice--a brief review and observations. PMID- 1291470 TI - Atlas of cancer incidence in the former German Democratic Republic 1978-1982. PMID- 1291471 TI - Fumbling with the Friedewald formula. PMID- 1291472 TI - Effect of yoga training on reaction time, respiratory endurance and muscle strength. AB - There is evidence that the practice of yoga improves physical and mental performance. The present investigation was undertaken to study the effect of yoga training on visual and auditory reaction times (RTs), maximum expiratory pressure (MEP), maximum inspiratory pressure (MIP), 40 mmHg test, breath holding time after expiration (BHTexp), breath holding time after inspiration (BHTinsp), and hand grip strength (HGS). Twenty seven student volunteers were given yoga training for 12 weeks. There was a significant (P < 0.001) decrease in visual RT (from 270.0 +/- 6.20 (SE) to 224.81 +/- 5.76 ms) as well as auditory RT (from 194.18 +/- 6.00 to 157.33 +/- 4.85 ms). MEP increased from 92.61 +/- 9.04 to 126.46 +/- 10.75 mmHg, while MIP increased from 72.23 +/- 6.45 to 90.92 +/- 6.03 mmHg, both these changes being statistically significant (P < 0.05). 40 mmHg test and HGS increased significantly (P < 0.001) from 36.57 +/- 2.04 to 53.36 +/- 3.95 s and 13.78 +/- 0.58 to 16.67 +/- 0.49 kg respectively. BHTexp increased from 32.15 +/- 1.41 to 44.53 +/- 3.78s (P < 0.01) and BHTinsp increased from 63.69 +/- 5.38 to 89.07 +/- 9.61 s (P < 0.05). Our results show that yoga practice for 12 weeks results in significant reduction in visual and auditory RTs and significant increase in respiratory pressures, breath holding times and HGS. PMID- 1291473 TI - Effects of undernutrition and sex difference on skeletal muscle function in young rats. AB - The effects of undernutrition and sex difference on skeletal muscle contractile characteristics were studied in young albino rats. The skeletal muscle (gastrocnemius) of 8 week old pups with only one-third normal food intake (undernourished group = UN group; n = 18), as compared to free fed pups (control group = cont. group; n = 16), showed prolongation of contraction time (23.6 +/- 1.0 Vs 20.9 +/- 0.8 msec, Mean +/- SE, P < 0.05) and relaxation time (31.5 +/- 1.8 Vs 22.9 +/- 1.1 msec, P < 0.001) and retention of contraction force and endurance time. In 18 week old rats the effects of sex difference in females (n = 10), as compared to males (n = 10) were prolongation of contraction time in gastrocnemius (32.2 +/- 1.5 Vs 27.8 +/- 1.5 msec, P < 0.05), less force production in gastrocnemius (668.9 +/- 48.0 Vs 895.4 +/- 93.3 g, P < 0.05) and extensor digitorum longus (20.1 +/- 3.3 Vs 29.9 +/- 2.5 g, P < 0.05) and shorter endurance time (160.8 +/- 10.2 Vs 187.2 +/- 7.1 sec, P < 0.05) in soleus. Thus, it is concluded that early undernutrition has prolonged the contraction and relaxation times of the skeletal muscles and the effect of sex difference in the early adulthood was different in different skeletal muscles. PMID- 1291474 TI - Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin. AB - Effect of oral administration of curcumin (diferuloyl methane) on lipid peroxidation in various organs of mice like liver, lung, kidney and brain was studied in control animals as well as those given carbon tetrachloride, paraquat and cyclophosphamide. Oral administration of curcumin significantly lowered the increased peroxidation of lipids in these tissues produced by these chemicals. Administration of curcumin was also found to lower significantly the serum and tissue cholesterol levels in these animals, indicating that the use of curcumin helps in conditions associated with peroxide induced injury such as liver damage and arterial diseases. PMID- 1291475 TI - Differential role of ovarian hormones for taste preferences in rats. AB - The effects of estrogen (OVX-EB) and progesterone (OVX-P) administration to ovariectomized (OVX) rats on food and fluid intakes were studied in fifty five animals grouped into three series. Animals in each series were given a choice of two fluids viz. tap water and either 5% glucose (5 G/W) or 12% glucose (12 G/W) or 1.5% Sodium chloride (S/W) by two bottle preference. Both hormones had a differential effect on the ingestion of the two concentrations of glucose while progesterone markedly increased the intake of Sodium Chloride. Could the putative role of the ovarian hormones be hedonic for glucose and homeostatic for salt? PMID- 1291476 TI - Pharmacological screening of few new 2-(substituted acetyl) amino-5-alkyl-1,3,4 oxadiazoles. AB - Nine new 2-(substituted acetyl) amino-5-alkyl-1,3,4-oxadiazoles were synthesised and confirmed on the basis of IR and nitrogen analysis. These were screened for spasmolytic, anti-inflammatory and their effects on blood pressure after determining ALD50. Compounds GK-4 i.e. 2-(diethylaminoacetyl)- amino-5-methyl 1,3,4-oxadiazole and GK-8 i.e. 2-(din-propylamino acetyl)-amino-5-ethyl-1,3,4 oxadiazole were found to be spasmolytic. Compound GK-6 i.e. 2 (diethylaminoacetyl)-amino-5-n-propyl-1,3,4-oxadiazole was found to be a potent hypotensive agent with the effect lasting for more than two hours. PMID- 1291478 TI - Background noise in healthy volunteers--a consideration in adverse drug reaction studies. AB - In adverse drug reaction studies proper control over 'Back ground noise' is to be maintained to avoid erroneous conclusions to be drawn for adverse drug effects. Healthy volunteers, not taking any medication, were surveyed by a questionnaire to obtain data on the occurrence of any symptoms, often ascribed to side effects of drugs. Only 62 subjects out of a total of 236 (26.27%) stated experiencing none of these symptoms during the previous 3 days. The remaining subjects reported some symptoms, with an median number of symptoms experienced per person being 2; the most common being fatigue; headache, inability to concentrate and excessive sleepiness. PMID- 1291477 TI - Chronopharmacokinetics of rifampicin. AB - Chronopharmacokinetics of rifampicin was studied in four healthy adult male human volunteers after drug (2.0 g) ingestion at 6.00, 12.00, 18.00 and 24.00 hr. The absorption rate constant was found to be lower and the time to reach peak concentration was longer after drug administration at 24.00 hr than at other dosing times. A second peak was observed in all individual volunteers between 6 12 hr after drug dosing at 24.00 hr. This may be due to the influence of biliary rhythms on the disposition kinetics of rifampicin. PMID- 1291479 TI - Sex variation in ascorbic acid catabolism. AB - Male and female albino rats of same age and body weight were pair fed with laboratory stock diet and ascorbic acid, dehydroascorbic acid and diketogulonic acid were determined in the liver and urine, while in blood only ascorbic acid was estimated. Male rats had concentration higher of ascorbic acid in liver and urine as compared with females, while there were no significant variations in the contents of dehydroascorbic acid and diketogulonic acid. Hepatic and renal 2, 3 diketoaldonate decarboxylase, and hepatic dehydroascorbatase were also found to be significantly higher in male rats. Similar sex variations were also observed in ascorbic acid catabolism in guinea pigs without any differences in urinary ascorbic acid contents. PMID- 1291480 TI - Poor reliability of the first meal tolerance test. AB - The poor reproducibility of oral glucose tolerance test (OGTT) has been known for a long time. Some recent reports indicate that postprandial glycaemia achieved during the test is likely to be higher on the first occasion than on subsequent visits. We have analysed our recent data on meal tolerance tests (MTT) from this angle. Fifteen healthy subjects and 9 subjects having NIDDM were administered two essentially identical meals one or two weeks apart. In case of healthy subjects, the absolute as well as incremental postprandial glycaemia achieved at 0.5 h and 1.0 h on the first visit was significantly higher (P < 0.05) than on the subsequent visit. The effect of visit was insignificant in case of NIDDM subjects. The effect observed in healthy subjects may be due to the release of adrenaline during the first visit brought about by apprehension. In NIDDM subjects the apprehension is likely to be much less because of their having undergone such tests in the past. Hence a single casual OGTT or MTT is unreliable as a diagnostic tool in borderline cases of impaired glucose tolerance test. The test needs to be repeated at least once more to eliminate false positives. PMID- 1291481 TI - Behavioural change in rats due to chronic oral and systemic formaldehyde. AB - Impact of chronic formaldehyde exposure in respect of route on behaviour was studied. Preconditioned (environmental) male albino rats (340-400 g) in 3 groups (n = 5) under 60 days oral and systemic exposure to 10 mg/kg/day HCHO were examined for their behavioural performance (i.e. short term memory) in Cook's apparatus. Twenty percent rats settled in grade III (unconditioned avoidance response) in the i.p. (i.e. systemic group) whereas in oral fed (HCHO route in drinking water) rats, 60% settled in grade II (conditioned avoidance response) at the end of sixty days. PMID- 1291482 TI - Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. AB - The effect of curcumin administration in reducing the serum levels of cholesterol and lipid peroxides was studied in ten healthy human volunteers, receiving 500 mg of curcumin per day for 7 days. A significant decrease in the level of serum lipid peroxides (33%), increase in HDL Cholesterol (29%), and a decrease in total serum cholesterol (11.63%) were noted. As curcumin reduced serum lipid peroxides and serum cholesterol, the study of curcumin as a chemopreventive substance against arterial diseases is suggested. PMID- 1291483 TI - Reticuloendothelial function in acute noise stress. AB - Wistar strain albino rats of either sex were subjected to acute noise stress (3000 Hz at > 97 dB) for 30 minutes. Carbon clearance test was conducted in noise stressed animals immediately after the stress period. Significant (P < 0.001) increase of the clearance constant K was observed in stressed animals compared to the controls, indicating increased phagocytic activity of the reticuloendothelial system. PMID- 1291484 TI - Evaluation of some 1,2,4-dithiazolidines as anticonvulsant agents in Wistar rats. PMID- 1291485 TI - Influence of ethyl and methyl alcohol on rat brain histamine content. PMID- 1291486 TI - Heart rate alterations in different types of pranayamas. PMID- 1291487 TI - Acetylcholine and cholinesterase levels in the brain of methanol treated rats. PMID- 1291488 TI - Antiinflammatory and acute toxicity studies with the leaves of Vinca rosea Linn in experimental animals. PMID- 1291490 TI - Recent trends in management of thyroid disorders. PMID- 1291491 TI - Primary prevention of atherosclerosis: responsibility of the pediatrician? PMID- 1291489 TI - Heart rate and respiratory changes accompanying yogic conditions of single thought and thoughtless states. PMID- 1291492 TI - An epidemiological study of febrile seizures with special reference to family history and HLA linkage. AB - One hundred and forty four cases of febrile seizures, 95 simple (typical) and 49 complex (atypical); were studied and compared for clinical and epidemiological data and family history of febrile and afebrile seizures. Major results were: maximum age of onset below three years (75%) in both simple and complex groups, male preponderance, respiratory infection as the commonest etiology (69.4%) and maximum seizure onset within 24 hours of fever (73%). The familial prevalence of all seizures was 29.1%, 23.2% in the simple and 40.8% in the complex group (p < 0.01). The familial prevalence of febrile seizures was 20%; similar in both groups. The familial prevalence of afebrile seizures was 13.9%; 6.3% in simple and 28.6% in complex group (p < 0.01). The commonest relative was a sibling (13.2%). The prevalence in parents was 4%. Families with two additional members with history of seizures revealed complex seizure patterns in two-thirds of index cases. There was no correlation between family history of seizures and age at onset or sex. No clear inheritance pattern emerged and polygenic inheritance is likely. One third of eighteen families had siblings with identical segregation of parental HLA-A and B haplotypes. Five families showed the presence of HLA All. This small though adequate sample size did not reveal an HLA marker for febrile seizures. PMID- 1291493 TI - Parental attitudes towards epilepsy. AB - Parents of 352 children with history of epilepsy were interviewed by a pretested, open ended questionnaire to ascertain the nature of first aid care during an epileptic fit, complications arising out of this care, and parents' perceptions regarding causes of epilepsy. The commonest form of care provided was to force liquids by mouth (50.6%), followed by pressure over body to restrain convulsive movements (13.0%) or to put some object to force the teeth open (11.9%). The various causes of epilepsy according to the parents were: due to an evil spirit (26.7%0, heritable causes (13.9%), physical or mental weakness (6.6%) and brain damage (5.9%). The need of imparting knowledge and clear understanding about epilepsy among parents is emphasized. PMID- 1291494 TI - Subclinical group A streptococcal throat infection in school children. AB - Seven hundred and forty nine apparently healthy school children aged 5-15 years were investigated for throat infection with Group A streptococci (GAS) during December 1990 to May 1991. The prevalence of beta hemolytic streptococci (BHS) was 18.8%; most organisms belonged to Group A streptococci (13.7%). The prevalence of BHS in throat was significantly higher (p < .001) in girls as compared to boys. Immune response to extracellular antigens was studied in 53 children who had GAS strain in their throat, 54.7% had elevated titers of antistreptolysin O or antideoxyribonuclease B or both indicating subclinical infection with GAS. Thus it is recommended that serological examinations should be done along with throat culture to identify subclinical Group A streptococcal throat infection. PMID- 1291495 TI - Carnitine supplementation in diphtheria. AB - We studied the effect of carnitine supplementation in patients with diphtheria. Six hundred and twenty five children of diphtheria received either DL-carnitine (100 mg/kg/day in two divided doses orally for four days), or no carnitine, in addition to the routine treatment for diphtheria. The patients receiving carnitine (n = 327) and controls (n = 298) were matched for age, sex, duration of symptoms, grade of toxemia and immunization status. Patients receiving carnitine showed a significant reduction in incidence of myocarditis as compared to controls (p = 0.001). Cases with myocarditis receiving carnitine therapy showed a significant reduction in mortality as compared to controls (p < 0.001). In view of a significant decline in incidence and mortality of myocarditis in cases of diphtheria, we recommended that all cases with diphtheria should receive carnitine supplementation. PMID- 1291496 TI - Effects of maternal labetalol on the newborn infant. AB - Forty eight neonates, born to mothers suffering from pregnancy induced hypertension and receiving labetalol for control of blood pressure, were studied for the possible adverse effects of the drug. These were compared with eighty one neonates matched for gestation and weight and born to mothers with pregnancy induced hypertension treated with drugs other than labetalol. Incidence of birth asphyxia and intrauterine growth retardation (IUGR) in the study population was 10.4 and 22.9%, respectively and in the control group 5 and 19.7%, the difference between two groups was not statistically significant (p > 0.05). However, the incidence of hypoglycemia was significantly higher (p < 0.01) in the study group (47.9%) as compared to the control group (17.2%). Two-thirds of the hypoglycemic babies in the study population were asymptomatic and they were managed with sugar fortified milk feeds. In the study population, the symptomatic hypoglycemic babies had hypoglycemia for prolonged duration of 43.3 +/- 23.3 hours as compared to 11.5 +/- 6.3 hours in symptomatic hypoglycemic babies of the control group (p < 0.01). The mothers of the symptomatic babies in the study group received higher doses of labetalol in the range of 287.6 +/- 142.3 mg/day while rest of the mothers in the same group whose babies had either asymptomatic hypoglycemia or normal blood glucose levels, received 239.5 +/- 118.5 mg/day, though the difference was not statistically significant. It is concluded that maternal labetalol therapy is associated with increased risk of neonatal hypoglycemia. PMID- 1291497 TI - Acceptability trials with ready to eat foods in a rural area. AB - Acceptability trials with three types of recipes was carried out on 184 young preschoolers (6 months to 35 months) residing in four nearby villages around Hyderabad. Results of this study indicated that among the 3 types of supplementary foods (Sweet Ready Mix, Sweet Ready Mix with Amylase and Therapeutic food tested here, the Therapeutic food was more acceptable (taste, smell and bulk) to the children. The criteria for acceptability of the food was defined as the ability of 75% of the children to consume 75% or more of the food supplement at one sitting for 70% of the days of the trial. The Therapeutic food, a calorie dense supplement, met the above criteria. The acceptability was poor for the Sweet Ready Mix and Sweet Ready Mix with Amylase (< 4%) mainly due to quantity rather than taste and smell as revealed by the mothers. The mothers of the children also liked the taste and smell of the therapeutic food better. Consumption of the therapeutic food caused minimal side effects like diarrhea and vomiting when compared to side effects after eating Sweet Ready Mix and Sweet Ready Mix with Amylase in children. PMID- 1291498 TI - Risk factors for fatal pneumonia: a case control study. AB - We conducted a case control study to identify the risk factors for death among hospitalized children with acute pneumonia at the Institute of Child Health, Madras. All the 70 patients who died of pneumonia constituted the case--patients and 140 children recovered from pneumonia, selected by systematic sampling, during the same period served as controls. By univariate analysis, the risk factors for death in pneumonia observed were associated illnesses--Odds Ratio (OR) 22.2. (95% confidence interval [CI] 9.8-51.4; p = < 0.001); congenital anomalies--OR 10.4 (2.9-37.8; p = < 0.001); severe pneumonia--OR 4.2 (1.2-14.4; p = 0.09); marasmic status--OR 2.9 (1.5-5.7; p = 0.001); age under 6 months--OR 2.8 (1.3-5.7; p = 0.004); and severity of the pneumonia (lobar versus segmental)--OR 2.0 (0.9-4.5; p = 0.09). By logistic regression analysis the following risk factors were significant--associated illnesses. (51.6; 18-146.9; p = < 0.001); age under 6 months (6.5; 2-20.6; p = < 0.001), marasmic status (5.8; 2.2-15.6; p = < 0.001); and congenital anomalies (3.8; 2.0-7.1; p = < 0.001). These risk factors should be kept in mind by the clinicians for appropriate intervention at an earlier stage to minimize death. PMID- 1291499 TI - Breastfeeding and weaning practices in relation to nutritional status of infants. AB - During the critical period of infancy, breastfeeding and weaning practices play an important role in determining the growth of an infant. The present study investigates the issue by observing 225 infants from Low Socio Economic (LSE) class (n = 150) and High Socio Economic (HSE) class (n = 75) for weight, height, and feeding practices. Almost all artificially fed (AF) infants in LSE class were malnourished while this was not so in the HSE class. However, the proportion of malnourished children in the LSE class for partially breastfed (BF + AF) group was comparable with exclusively breastfed (BF) group and was significantly lower (p < 0.01) than AF group indicating protective effect of partial breastfeeding against risks of contamination associated with weaning foods in such communities: The real bottleneck thus appears to be the lack of knowledge of handling and giving weaning foods in adequate quantities. Educating mothers appears to be the meaningful solution for improving the nutritional status of infants in poor communities. PMID- 1291500 TI - Lactation failure. AB - Seventy five mothers with lactation failure were studied, whose less than 4-month old babies were admitted to the hospital. Partial lactational failure (94.7%) was noted more often than complete lactational failure (5.3%). Initiation of breastfeeding was delayed for 2 to 5 days usually for traditional reasons (77.3%) and because the mothers felt that the milk output was inadequate (92%). The various causes of lactation failure were determined and the relationship to various factors was analyzed. The commonest cause of lactation failure was insufficient milk or no milk (80%). The age, parity, education, socio-economic status, religion, family structure and urban vs rural status of mother--all had a bearing on the occurrence of lactation failure. An attempt was made to relactate all these mothers. The outcome was successful in 69.3 cases and failed in only 4% cases. In 26.7% cases, we cannot predict the outcome as the mothers hospital stay was very brief with no follow up. PMID- 1291501 TI - Pseudohypoparathyroidism. PMID- 1291502 TI - Isosexual male precocity due to a Leydig cell tumor. PMID- 1291503 TI - Acute infectious thrombocytopenic purpura and circulatory failure--is it dengue shock syndrome? PMID- 1291504 TI - Plasma cell granuloma of the lung. PMID- 1291505 TI - Nutritional status of tribal and urban slum preschool children (3-4 years). PMID- 1291506 TI - Glomerulonephritis in congenital syphilis. PMID- 1291507 TI - Idiopathic hypertrophic osteoarthropathy. PMID- 1291508 TI - Schizencephaly--imaging by MRI. PMID- 1291509 TI - Ileal atresia with intestinal duplication. PMID- 1291510 TI - Hemoperitoneum secondary to splenic rupture in a neonate. PMID- 1291511 TI - Antenatal diagnosis of bowel atresia. PMID- 1291512 TI - Conservative management of extreme low birth weight quadruplets. PMID- 1291513 TI - Neonatal syphilis with glaucoma and periosteitis. PMID- 1291514 TI - Tongue-tie: myths and truths. PMID- 1291515 TI - Present status of neonatal care in India. PMID- 1291516 TI - Acute peritoneal dialysis in newborn babies. PMID- 1291517 TI - National nutrition supplementation programmes. PMID- 1291519 TI - The radiographic incidence of multiple roots and canals in human mandibular premolars. AB - The aim of this study was to investigate the incidence in mandibular premolars of multiple roots and root canals that could be demonstrated radiographically. The images of mandibular premolar teeth as seen on intraoral full-mouth radiographic surveys (547) taken with the paralleling technique were examined. In 99 patients (18.1%) there was at least one premolar tooth with either divided canals or roots. First premolars were involved in 15.7% of patients, and second premolars in 7%. PMID- 1291518 TI - Influence of surgical treatment of periapical lesions on serum and blood levels of inflammatory mediators. AB - Changes in the serum levels of immunoglobulin IgA, IgG, IgM, positive acute phase proteins and complement activity, as well as the lymphocyte subpopulations and the neutrophil leucocyte-related chemiluminescence in the blood of patients with apical granuloma as related to endodontic and surgical treatment were investigated. Measurements were performed on admission, and 7 days and 3 months after the treatment. Elevated IgM concentration, positive acute-phase protein levels and spontaneous whole-blood chemiluminescence were noted at admission. However, a significant decrease in the serum level of each of the six investigated acute-phase proteins, and in the spontaneous chemiluminescence of blood was observed during the 3-month follow-up period. The significant increase in serum complement activity following therapy suggests that complement fixation might have occurred in these patients. A significant increase in the ratio of early sheep erythrocyte rosette-forming lymphocytes was also observed. The results of this study provide evidence for complete recovery after elimination of local inflammation by proper endodontic treatment and apicectomy in patients with apical granuloma. PMID- 1291520 TI - The use of glass ionomer as a root canal sealer--a pilot study. AB - The use of a resin-based glass ionomer as an endodontic sealer was studied in vitro. The root canals of extracted single-rooted human teeth with mature apices were prepared using a stepback technique. Subsequently, the smear layer was removed with 40% citric acid and the canals obturated using lateral condensation of cold gutta-percha and a resin-based glass ionomer as the sealer. The relationship between the sealer and the wall of the root canal was studied using scanning electron microscopy. The shear bond strength of gutta-percha to this glass ionomer was also determined. Finally, the uptake of fluoride into the wall of the root canal was studied using scanning electron microprobe analysis after storage for 2 weeks, 1 month and 3 months following root filling with gutta percha and glass ionomer cement. The results showed that removal of the smear layer allowed the sealer to enter some of the dentinal tubules. This was observed most frequently in the middle third of the root canal, where there was good adaptation of the sealer. The shear bond strength of gutta-percha to the glass ionomer sealer was not significantly different from that obtained between gutta percha and a proprietary zinc oxide-eugenol endodontic sealer. The concentration of fluoride in the dentine in the coronal part of the root canal increased after obturation with gutta-percha and the glass ionomer sealer at every time interval. The increase in fluoride concentration varied widely between teeth. It is concluded that a resin-based glass ionomer cement may have potential as a root canal sealer. PMID- 1291521 TI - The effect of smear layer upon the coronal leakage of gutta-percha fillings and a glass ionomer sealer. AB - The effect of the removal of the smear layer on coronal leakage of root fillings was studied using two sealer cements. Sixty single-rooted teeth with mature apices were prepared chemomechanically using a modified double-flared technique with non-cutting tipped files and copious irrigation with 2% sodium hypochlorite. The teeth were randomly allocated to four groups of 15 teeth each. Two groups were treated with 40% citric acid to remove the smear layer. Two groups of teeth, one with and one without smear layer, were filled by lateral condensation of gutta-percha with either Tubliseal or a resin-based glass ionomer, Vitrebond. The teeth were stored for 1 week, thermocycled, and the extent of coronal leakage determined for each group after immersion in Indian ink for 90 h. The teeth were demineralized, dehydrated and immersed in methyl salicylate which rendered them transparent. Linear measurement of dye penetration was recorded. The mean depth (+/- SD) of leakage for the groups in which the smear layer was left intact was 4.26 +/- 1.53 mm and 6.83 +/- 1.65 mm for the Vitrebond and Tubliseal, respectively. When the smear layer had been removed, the mean depth of leakage for the Vitrebond group was 1.13 +/- 0.29 mm, and 3.72 +/- 1.23 mm for the Tubliseal group. There was a statistically significant difference in leakage between the groups (P < 0.001). With both sealers, those teeth in which the smear layer had been removed showed less leakage than the specimens in which the smear layer was left intact (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291522 TI - Human pulpectomy: incidence of postoperative pain using two different intracanal dressings. AB - A clinical study using vital maxillary central incisors was performed to evaluate the incidence of postoperative pain after pulpectomy and dressing with a corticosteroid-antibiotic preparation or a calcium-hydroxide paste. Sixty teeth from 45 patients were prepared and dressed on the first visit and re-evaluated 7 days later. No difference was observed in the incidence of postoperative pain between the two groups. PMID- 1291523 TI - Mandibular premolar with three root canals--two case reports. AB - The presence of three root canals in the mandibular premolar may sometimes be recognized when there is persistent postoperative discomfort following root canal therapy. This paper presents two cases of root canal treatment of mandibular premolars with three root canals including one mandibular first premolar and one mandibular second premolar. The possibility that there is more than one root canal in lower premolar teeth must be considered in the radiographic and clinical examination during root canal treatment. PMID- 1291524 TI - [Work absenteeism of the nursing personnel of Valencia hospitals]. AB - A survey was carried out on a sample of 973 nurses from hospitals in the Valencian Region. The objective was to study work absenteeism due to health reasons depending on socio-demographic factors, work organization and self perception of health status. Information was collected by means of a self administered questionnaire. Duration and frequency of absenteeism was analysed over the previous twelve months. A 34.4% of female nurses and 35.4% of male nurses reported at least one episode, with an average length of 21 and 26 days respectively. There is a relation between absenteeism and self-perception of health status. We did not find man/woman differences with regards to absenteeism. PMID- 1291525 TI - [The association between regular alcohol consumption and accidents]. AB - The traffic accidents prevention in the direction of attempting to limit drinking driving behaviour is difficult to implement. However, if there was a relationship between these accidents and the regular consumption of alcohol, the reduction of alcohol use should be promoted. Likely, this strategy would be useful to other accidents. This study evaluates the association between regular consumption of alcohol and the occurrence of any type of accidents, a traffic accident, a home accident and an occupational accident. The information source has been interviews carried out to persons 16 years and older in National Health Interview Survey. In occupational accidents only interviews of men between 16 and 64 years of age have been used. The odds ratio (OR) calculated by logistic regression was the measure of association used. Except for home accidents, the results show statistically significant OR for the 16 to 24 and 25 to 44 age groups. For the occurrence of any type of accident, the ORs for the 16 to 24 years age group were: 1.37 for moderate drinkers, 1.87 for great drinkers and 2.55 for heavy drinkers, and the ORs for the 25 to 44 years age group were 1.28, 1.65 and 2.11 for the same levels of consumption. Similar magnitude of association showed the traffic and occupational accidents. In all cases interaction between regular consumption of alcohol and age was found. Our results suggest that a new direction in the health policy of accidents should be developed. PMID- 1291526 TI - [Mortality from cancer of the breast and the female genitalia in Aragon, 1975 1984]. AB - One out of four cancer deaths in women are due to breast cancer and female genital cancer. Mortality data are a basic information source to study disease characteristics in the population. A descriptive study on breast and female genital cancer mortality was carried out in Aragon covering the period 1975-84. Geographical differences and variations on mortality rates between the periods 1980-84 and 1975-79 have been studied. A mortality rate of 40.2 per 100,000 women per year has been observed for these tumours. Breast cancer accounted for 55% of these deaths. Reduction of mortality rate was seen for uterus non-specified between the periods 1980-84 and 1975-79, probably due to an improvement in quality of death certificates for uterus cancer. Higher mortality rates have been observed in the town of Zaragoza than in other parts of Aragon. This suggests the town of Zaragoza as priority in strategies of prevention and control programs. PMID- 1291528 TI - [Physical exercise and health promotion in childhood and youth]. AB - The "new health consciousness" that emerged in the developing countries in the 70s and 80s, has contributed to consider exercise as an element of health promotion. But it can establish simplistic relationships between exercise and health, particularly critical for professionals who develop promotion programmes. In this paper, five problematic aspects linked, to exercise and health relationships both in children and youngsters, are discussed and should be taken into account when promoting health programmes. We refer to: 1) the problematic role of exercise in health promotion and in physical education curriculum as an area of privileged action in children and youngsters; 2) the automatic relationship between fitness and health, when the former addresses to high levels of performance and the later is linked to moderate, regular and frequent exercise; 3) problems of fitness tests as a measure of health-related physical activity; 4) the assumption that any kind of physical activity is health-related; and 5) the quantity of exercise necessary for health as a practical problem. From the discussion different proposals are offered in order to develop health-related exercise promotion programmes such as to consider the risks of doing physical activity as a criteria to select exercises; to emphasize the qualitative instead of quantitative aspects of practice; to reconceptualize fitness and sport towards a health focus; to include a broad range of activities which offer the opportunity to every child and youngster to participate; to reduce the importance of testing in evaluation programmes; and other educational considerations which can help to maintain exercise practice beyond the schooling period. PMID- 1291527 TI - [The knowledge of the obligatory reporting of diseases among health professionals]. AB - In order to assess what different health care workers (mainly physicians and nursing staff) know about the reporting of communicable diseases, with special emphasis on diseases that must be urgently reported, four groups were interviewed about this health information system (91 persons, who took part in different Public Health Seminars during the periods 1989-90 and 1990-91). The total mean score was 16.6 +/- 5.2, in a quantitative scale ranging from 0 to 27 points. Cholera was the communicable disease with the highest percentage of correct answers concerning the knowledge of its reporting (100% in two groups), while typhus was the disease with the lowest percentage (23%). The diversity of the results within the study groups suggests that it is necessary to insist on a continuous training on epidemiological surveillance and communicable diseases within Public Health activities in Catalonia. PMID- 1291529 TI - [Primary health care: an analysis of the transition in Anadalucia]. AB - The article develops an analysis of the process of transformation of primary health care in Andalucia (Spain), related to two fundamental aspects. On the one hand, the strategic aspects of reform are analysed, inspiring principles, as well as legislation and administration. So called "central" changes, that is, those that really suppose transformations in the services: geographic distribution, donation, organisation, human resources, etc., are also analyzed. The second aspect approached is an analysis of the situation of the system related to the limitations and malfunctions, important conditioners of the present functioning and immediate future of primary care. PMID- 1291530 TI - Assessment of vitamin A deficiency in a rural area in Mali. Estimation of sample size for the impression cytology test. AB - The prevalence of vitamin A deficiency among two to ten years old children in a rural area of Mali was assessed by ophthalmic examination, determination of plasma retinol levels and impression cytology with transfer tests. A Public Health problem of vitamin A deficiency was identified in this rural area by: the prevalence of nightblindness significantly (p < 0.001) above the cut-off (1%) defined by the World Health Organization (WHO); the prevalence of corneal scarring significantly (p < 0.001) above the WHO's cut-off (0.05%); the percentage of subjects with plasma retinol levels below 0.35 mumol/l (10 micrograms/dl) significantly (p < 0.001) higher than the WHO's threshold (5%); and 52.8 +/- 8.2% children with "Abnormal" impression cytology as determined by the impression cytology test (IC). This preliminary survey confirmed widespread vitamin A deficiency in Mali. The minimum sample size required for a study using the impression cytology test to determinate a Public Health problem in a population was calculated for different situations. Ophthalmic examination indicated a very high rate of active trachoma (29.6 +/- 7.0%), and a relationship between active trachoma and impression cytology results was identified. PMID- 1291531 TI - Chemical synthesis, growth-promoting activity, and metabolism of all-trans retinyl beta-glucose in the rat. AB - Reaction of all-trans retinol with alpha-D-glucopyranosyl bromide tetrabenzoate in the presence of silver carbonate gave all-trans retinyl beta-glucose in good yield. Depending on the mode of administration, retinyl beta-glucose, which is soluble in water, showed 67-100% of the growth-promoting activity of retinyl acetate in vitamin A-deficient rats. In metabolic studies on vitamin A-deficient rats, retinyl beta-glucose was rapidly hydrolyzed to retinol. The possible therapeutic uses of retinyl glucose are discussed. PMID- 1291532 TI - The influence of dietary intake and sunlight exposure on the vitamin D status in an elderly Spanish group. AB - Traditional dietary habits and the living style in Spain should theoretically be enough to assure a healthy vitamin D status: a very high fish intake and one of the highest sun exposure rates of all countries in Europe. However, in spite of this, there is a high percentage in the elderly showing low vitamin D serum values. This paper is part of the Euronut-SENECA study, a major multicentre survey assessing the nutritional status in the elderly from 19 centres over 12 countries in Europe. In it, the vitamin D status in 55 healthy individuals from Spain has been studied and assessed by measuring dietary and supplemental vitamin D intakes; the influence of sunlight exposure such as physical activity, permanence in the sun, clothing, etc.; and 25-hydroxyvitamin D [25 (OH)D] serum concentration. The mean dietary intake was 1.3 +/- 1.5 micrograms/day, being fish, and specially fatty fish, the main source (62%). Of the total, 85% of the elderly did not reach the Spanish recommended dietary intake (2.5 micrograms/day). The mean 25(OH)D serum level was 25 +/- 14.7 nmol/l and there was a high percentage with deficit (13%) (8.4 +/- 1.9 nmol/l) and marginal (62%) (19.8 +/- 4.2 nmol/l) levels. People who usually walked 1.9 +/- 1.3 hours/day or stayed in the sun "every day" or "as much as possible", had higher (p < 0.05) serum 25 (OH)D concentrations (27.7 +/- 2.4 nmol/l and 31.3 +/- 3.7 nmol/l, respectively) than people who did not (16.6 +/- 1.2 nmol/l and 21.3 +/- 2.1 nmol/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291533 TI - Possible roles of vitamin E in immune response of calves. AB - The effect of vitamin E injections on immune responses of calves was investigated. Treatments were: 0, 900, 1800 and 2700 IU of D-alpha-tocopherol given by injection starting at birth and then a 3 wk interval until the age of 12 wk. Plasma vitamin E levels were significantly higher for supplemented calves than control calves at any of the sampling times. There were no significant differences in the concentrations of immunoglobulin IgG1, IgG2 and titre to Keyhole Limpet Haemocyanin among treatments. However, the general trend was to have higher concentrations of IgG1 and IgG2 with an increase in the levels of vitamin E. Immunoglobulin IgM was significantly higher for calves supplemented with 2700 IU of vitamin E than control calves. PMID- 1291534 TI - Determination of vitamins A and E in liver tissue. AB - A simple, efficient and robust method for the simultaneous determination of the two vitamins A and E in liver tissue has been developed and evaluated. The assay consists of a saponification step followed by a single extraction of the resulting solution with a mixture of n-hexane/toluene. The vitamins are quantified in the extract using two separate HPLC lines running on straight phase mode. The eluted compounds were detected with a fluorescence detector. Recoveries of spiked samples were found to be 92.4% for vitamin A and 95.2% for alpha tocopherol. The coefficient of variation was found to be +/- 4.27% for retinol and +/- 4.64% for alpha-tocopherol. The described analytical method has proven to be very effective and fast, enabling the processing of a large number of samples within a short period of time. It is highly specific and sensitive covering a wide range of different concentrations in the samples. It may be applied therefore in routine assays of samples with great variability concerning the vitamin concentrations in the tissue. PMID- 1291535 TI - Evaluation of ascorbic acid 2-O-alpha-glucoside as vitamin C source: mode of intestinal hydrolysis and absorption following oral administration. AB - Ascorbic acid 2-O-alpha-glucoside (AA-2G) has been reported to have antiscorbutic activity in guinea pigs. The present experiments examined the metabolic fate of AA-2G following ingestion. Oral administration of AA-2G (96 mg) to guinea pigs resulted in a remarkable increase of ascorbic acid in various tissues as well as plasma, but intact AA-2G was detected only in plasma, but intact AA-2G was detected only in plasma and urine in small amounts. The absorption efficiency of AA-2G and ascorbic acid was further determined by using everted gut sacs of rats. Ascorbic acid released from AA-2G on the mucosal side was effectively taken up across intestinal membranes into the serosal side, whereas AA-2G poorly permeated via a passive transport system. The hydrolysis of AA-2G on the mucosal surface of everted gut was completely inhibited by an alpha-glucosidase inhibitor and the hydrolytic activity of a crude membrane extract diminished to one-forth after immunoprecipitation with the antibody specific to maltase. From these results, it is concluded that ingested AA-2G serves as a vitamin C source through the hydrolysis by intestinal membrane-bound alpha-glucosidase, mainly maltase, and the subsequent absorption of released ascorbic acid. PMID- 1291536 TI - Lipid profile, anthropometry and dietary intake of 132 Thai vegetarians. AB - The anthropometric measurements, lipid pattern and dietary intake of 64 male and 68 female Thai vegetarians (mostly lacto-vegetarians) were investigated. 32 males and 36 females on an ordinary Thai diet served as controls. Nutritional anthropometric variables and serum lipid concentrations, which the exception of triglycerides, were found to be lower in the vegetarian group than in the control group. The vegetarians consumed more energy than the controls. No difference in the protein intake was observed in both groups. Fat intake was, however, lower and carbohydrate intake higher in the vegetarian group. Also in the vegetarian group, HDL-cholesterol fraction correlated negatively with anthropometric measurements. Other fractions show only a weak correlation, if at all, in this group. A good correlation to all serum lipid variables determined to anthropometric measurement was observed in the control group. PMID- 1291537 TI - Change in cholesterol levels and in lipid fatty acid composition in safflower oil fed lambs. AB - The influence of safflower oil supplemented (5%) diet both on cholesterol level and on lipid fatty acid composition was investigated in serum, liver and muscle (Longissimus dorsi) of lambs. The fatty acid pattern varied similarly in all the three tissues. An increase in linoleic acid and in some other polyunsaturated fatty acids, and a simultaneous reduction of the saturated fatty acids (mostly palmitic and stearic acid) were observed. On the contrary, cholesterol content decreased notably (44%) in the liver, with a much less evident decrease in serum and muscle of treated animals. PMID- 1291538 TI - Influence of a natural-ingredient diet containing Phaseolus vulgaris on the colonization by segmented, filamentous bacteria of the small bowel of mice. AB - The appearance of segmented, filamentous bacteria (SFBs) in the small bowel of mice is influenced by the composition of the diet, but the dietary components responsible are not known. The addition of ground, whole Phaseolus vulgaris to a natural-ingredient diet at the expense of part of the skim milk powder, ground barley and wheat middlings components, caused an increase of the colonization of the mouse small bowel by SFBs. This effect was not seen when whole Phaseolus was added to a purified diet at the expense of part of the casein, corn oil, coconut fat, corn starch, dextrose and cellulose components. In an attempt to identify the fraction of Phaseolus that might contain SFB-inducing substances, the skin and kernel fraction of the bean were added to the natural-ingredient diet. The skin and kernel fraction were found to be as effective in inducing SFB appearance as was whole Phaseolus. PMID- 1291539 TI - Effect of cadmium on the tissue levels of vitamin C in guinea pigs. PMID- 1291540 TI - The psychoanalytic envelope. PMID- 1291541 TI - A psychoanalytic study of eating disorders: I. A developmental profile of 67 index cases. AB - Much has been written in both the professional literature and lay press regarding the sociocultural basis for the current increase in eating disorders. The typical victims of these afflictions appear to be intelligent adolescent girls from middle and upper class families (Garfinkel and Garner, 1982). Although the general pressure for thinness, mastery, and achievement among women in our culture undoubtedly help shape the course of illness, these social mores do not appear to be its root causes. The data presented here suggest strongly that the truly eating-disordered individual has a history of disturbances in early relationships, leading to a lack of security and pronounced difficulties in trusting others, and in simply being an authentic individual in the presence of others. As such these individuals share many characteristics of others with severe personality disorders such as inner emptiness, problems with identity, fear of abandonment, and peer relationships (Clarkin et al., in press), but differ in the expression of these basic defects or in solutions found to compensate pathologically for these core deficiencies. Therefore, although contemporary cultural ideals and values may supply the shape of the disorder, these individuals would have fared badly in any social climate although their presentation of illness may have differed (Bemporad et al., 1988). It is this profound underlying personality pathology that necessitates prolonged treatment for any hope of amelioration. Later reports will address this indication with a description of the results of therapy. PMID- 1291542 TI - A psychoanalytic study of eating disorders: II. Intergroup and intragroup comparisons. PMID- 1291543 TI - Psychoanalysis and cognitive science: contrasting models of the mind. AB - Although the relationship between psychoanalysis and cognitive science has begun to be addressed, theorists have not constructed a unifying conceptual framework from which to compare and contrast these disciplines. This paper begins by considering the models of mind of cognitive science, and of classical and contemporary psychoanalysis. It is argued that it is useful to reformulate psychoanalytic constructs in terms of cognitive science models. Psychoanalysts have therefore become, and will continue to be, more cognitivist in their work. Nevertheless, psychoanalytic theory and practice is so fundamental that it constitutes the only starting point for clinical cognitivists. The reformulation of psychoanalysis in cognitivist terms is beneficial for both psychoanalysis and cognitive science. The explanatory power of the cognitivist remodelling of psychoanalysis can, of course, be fully assessed only once it has taken place. This paper encourages that theoretical work to proceed. PMID- 1291544 TI - The selfobject function of weapons: a self psychology examination. AB - Weapons serve a variety of functions, both for individuals and for society. One such function is that of a selfobject for narcissistically vulnerable persons. This selfobject function allows the damaged self to maintain cohesion and to offset feelings of vulnerability and powerlessness. Because the weapon allows the personality to feel in control and to exert dominance over others, it may come to be viewed in an idealized manner. This is very similar to the idealizing selfobject transference described by Kohut. Weapons are more likely to become selfobjects for those personalities suffering from some degree of self pathology. The selfobject function of weapons, however, may have significance beyond individual psychopathology. Groups of individuals, societies, and even nations may utilize weapons to counter feelings of vulnerability and to diminish fragmentation of the group's collective self. Their destructive potential may be unleashed in response to an intense narcissistic injury and narcissistic rage. The importance of weapons can thus be better understood by examining them within the context of self psychology. PMID- 1291545 TI - The darkling plain: a theoretical discussion of an antidote for depression. PMID- 1291546 TI - The role of the female therapist in the affirmation of gender in male patients. PMID- 1291547 TI - Insight and other psychotherapy change processes. PMID- 1291548 TI - Therapeutic responsibility in the case of Anne Sexton. PMID- 1291549 TI - The Anne Sexton biography: the limits of confidentiality. PMID- 1291550 TI - Listening at the keyhole: the Anne Sexton tapes. PMID- 1291551 TI - Legal issues in the Orne/Sexton case. PMID- 1291552 TI - The effects of living with violence. PMID- 1291555 TI - Freedom of choice: should I care? PMID- 1291554 TI - Third party payer systems. PMID- 1291553 TI - Single tooth replacement with a one-stage implant: case reports. PMID- 1291556 TI - Co-culture for embryo development: is it really necessary? PMID- 1291557 TI - Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. AB - Menopause is triggered by the number of ovarian follicles falling below a threshold number and is irreversible because oogonial stem cells disappear after birth. Since it is the result of programmed disappearance of a limited store of follicles, menopause can be predicted using mathematical models based on total follicle counts at different ages. Our model shows follicle numbers decline bi exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of -0.097 and a second of 0.237. The change occurred when numbers had fallen to the critical figure of 25,000 at age 37.5 years. The unexpectedly faster rate of ovarian ageing afterwards lowers the follicle population to 1000 at approximately 51 years, and was adopted as the menopausal threshold because it corresponds to the median age of menopause in the general population. Had the earlier rate persisted menopause would not be expected until 71 years. The impact of step reductions of follicle numbers on the prospective span of menstrual life was predicted by the model. A reduction by 50% before age 30 years resulted in the threshold being reached at 44 years and 0.6 year later for every subsequent year until age 37.5 years after which it is reached at 48 years. A reduction of 90% in childhood before age 14 years could result in menopause as early as 27 years, with increments of 0.6 year per year afterwards until after 37.5 years when it is expected at age 41 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291558 TI - Controlled preparation of the endometrium with exogenous oestradiol and progesterone: a novel regimen not using a gonadotrophin-releasing hormone agonist. AB - In women having inactive ovaries, controlled preparation of the endometrium has been achieved with exogenous oestradiol and progesterone. We report on the feasibility and practicality of using a similar regimen for timing transfers of cryopreserved embryos in women whose ovaries have not been suppressed. A total of 91 women having cryopreserved embryos from previous in-vitro fertilization (IVF) attempts received 4 mg/day of oestradiol valerate, starting on cycle day 1 of spontaneous (n = 85) or induced (n = 6) menstruation. A single blood sample was obtained on cycle day 14 for the measurement of plasma progesterone, oestradiol and luteinizing hormone (LH). Vaginal administration of micronized progesterone (300 mg/day) was started on day 15. Cryopreserved embryos were transferred on day 17 or 18 provided that day 14 plasma progesterone remained < or = 0.5 ng/ml, thereby confirming the absence of spontaneous ovulation prior to the administration of exogenous progesterone. Out of 91 cycles studied, plasma progesterone was found to be elevated (> 1 ng/ml) in only three (3.2%). Of the 88 scheduled transfers, 31 did not take place because no embryo survived thawing. In the remaining 57 cycles, 116 embryos were transferred resulting in 10 pregnancies, giving pregnancy and embryo implantation rates of 17.5 and 8.6% respectively. When a positive beta human chorionic gonadotrophin (HCG) titre was obtained, supplementation with oral oestradiol and vaginal progesterone was continued until placental autonomy was achieved. Of the 10 pregnancies, five (50%) were lost during the first trimester (biochemical, n = 1; miscarriage, n = 3; ectopic, n = 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291559 TI - Interactions between interferon gamma, tumour necrosis factor alpha, and interleukin-1 in modulating progesterone and oestradiol production by human luteinized granulosa cells in culture. AB - We have reported that the cytokines, interleukin-1 (IL-1), tumour necrosis factor alpha (TNF alpha), and interferon (IFN) alpha, beta, and gamma modulate the steroidogenic function of human luteinized granulosa cells in culture. In the present study we examined the interactions between these cytokines in modulating progesterone and oestradiol production by these cells. Neither IL-1 nor TNF alpha had significant effects on human chorionic gonadotrophin (HCG)-stimulated progesterone production, whereas IFN gamma (1-10 ng/ml) significantly reduced HCG stimulated progesterone production by 26-37%. Concomitant treatment with IL-1 (1 ng/ml) did not further enhance the inhibitory effect of IFN gamma on HCG stimulated progesterone production. In contrast, the combination of TNF alpha (1 ng/ml) and IFN gamma (10 ng/ml) acted synergistically to markedly inhibit HCG stimulated progesterone production by 81%. In addition, IL-1 and TNF alpha, neither of which was effective alone, acted synergistically to reduce significantly HCG-stimulated progesterone production by 30%. The combination of TNF alpha and IFN gamma also markedly inhibited follicle stimulating hormone (FSH)-stimulated oestradiol production by 97%, a significantly greater inhibition than that obtained with either cytokine alone. These results suggest that the cytokines may interact to modulate the steroidogenic function of luteal cells in the developing corpus luteum. PMID- 1291560 TI - Serum levels of free androstenedione, testosterone and oestradiol are lower in the follicular phase of conceptional than of non-conceptional cycles after ovarian stimulation with a gonadotrophin-releasing hormone agonist protocol. AB - Serum concentrations of total and free androstenedione, testosterone and oestradiol were followed during the follicular phase in women undergoing ovarian stimulation for treatment by in-vitro fertilization and embryo transfer (IVF-ET) and compared to those in natural unstimulated cycles. In addition, 10 conceptional and 18 non-conceptional cycles were compared in an attempt to understand the background for successful IVF cycles. The ultra-short gonadotrophin-releasing hormone agonist protocol was used for ovarian stimulation. Throughout the follicular phase, levels of total and free androstenedione and oestradiol were significantly lower in conceptional than in non-conceptional IVF cycles. In addition, levels of free testosterone during the follicular phase were significantly lower in women who conceived compared to non conceptional IVF cycles, whereas levels of total testosterone were similar. Levels of both free and total androstenedione increased significantly from the second day of the menstrual cycle until oocyte retrieval in non-conceptional IVF cycles, whereas levels in conceptional IVF cycles and unstimulated cycles showed no increase. On the day of oocyte retrieval levels of free and total androstenedione were significantly higher in non-conceptional IVF cycles than in conceptional IVF cycles and unstimulated cycles, which were similar. This study suggests that appropriate levels of free biologically active androgens and oestradiol are important parameters for successful conception.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291561 TI - Biological characterization of the isoforms of urinary human follicle-stimulating hormone contained in a purified commercial preparation. AB - The main physicochemical and biological properties of the several isoforms of urinary follicle-stimulating hormone (uFSH) present in a commercially available uFSH preparation were analysed. Purified urinary FSH was submitted to chromatofocusing and several immunoactive forms of uFSH with isoelectric points (pI) ranging from 5.5 to 3.8 were identified. An additional isoform was detected after passing through the chromatofocusing column a 1.0 M NaCl solution (salt peak). Each uFSH isoform or pool of neighbouring isoforms (pI value 5.5-5.1, pool I, 3.8 +/- 1.0% of total immunoactivity recovered; pI value 5.0-4.6, pool II, 18.4 +/- 3.6% of total; pI value 4.5-4.3, pool III, 14.9 +/- 1.5% of total; pI value 4.1, pool IV, 8.2 +/- 1.4% of total; salt peak, pool V, 51.1 +/- 6.4% of total) eluted as single FSH peaks after Sephadex G-100 exclusion chromatography (apparent M(r) 60,000). Even though FSH present within each pool was recognized by a receptor preparation, the receptor binding activity expressed as the radioreceptor assay/radioimmunoassay (RRA/RIA) activity ratio varied with the pI value of the particular uFSH isoform tested; starting from a pI value of 5.5, the receptor binding activity of FSH decreased from 5.9 +/- 0.39 to 2.4 +/- 0.19, as the pI value of the corresponding isoform declined. A similar trend was observed when the potency of each isoform was assessed by an in-vitro bioassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291562 TI - The clinical significance of antisperm antibodies in infertile couples. AB - Sera from 150 women and 162 men with unexplained infertility were examined using a commercial enzyme-linked immunosorbent assay (ELISA) kit for antisperm antibodies. The results were compared to those of the Friberg agglutination test, the post-coital test, the sperm-cervical mucus contact (SCMC) test and the pregnancy rate. We also tested follicular fluids obtained from 38 women who underwent in-vitro fertilization (IVF). These data were compared with those obtained in serum, post-coital test data and with the later development of the oocyte in IVF. Antibodies in follicular fluid were found only in women with antibodies circulating in serum. The correlation coefficient between these was 0.88 (P < 0.001). There was no correlation between antisperm antibodies in serum found with the ELISA test, and with the agglutination test, the post-coital test or the SCMC test. Neither was there any correlation between antibodies in follicular fluid and the post-coital test, the pregnancy rate or successful IVF. PMID- 1291563 TI - Prognostic factors in assessment and management of male infertility. AB - Evaluation of 304 infertile couples with at least one abnormal semen analysis (sperm density < 20 x 10(6)/ml and/or motility < 50%) and no apparent female factors was performed in a multicentre prospective cohort study. In 73 cases therapeutic donor insemination was performed (TDI group) with a resulting pregnancy rate of 48%. The remaining 231 couples (non-TDI group) had an overall pregnancy rate of 25%. The TDI group had a shorter duration of infertility. The ages of both partners were comparable in TDI and non-TDI groups. In the non-TDI group, univariate analysis resulted in identification of six clinical variables associated with a change in pregnancy rates. The strongest association was noted for length of infertility. There was a weaker association for semen volume, concentration of leukocytes in semen, history of pregnancy in the female partner and laparoscopy. Multiple variable analysis of data from the non-TDI group revealed that independent predictors of pregnancy were 'duration of infertility' and 'history of pregnancy in the female partner'. The multiple variable modelling suggested that (i) an increase in the length of infertility by 1 month prolongs the time to pregnancy by an additional 1.6% (95% confidence interval: 1.5-1.7%); and (ii) a history of past pregnancy in the female partner reduces the time of pregnancy by 51% (95% confidence interval: 47-56%). PMID- 1291564 TI - Chromosome anomalies in mouse zygotes treated by growth hormone-releasing factor. AB - The incidence of chromosome anomalies was studied in fertilized oocytes in two groups of hybrid mice in which superovulation was induced by gonadotrophins and growth hormone-releasing factor (GRF) supplementation or gonadotrophins alone (controls). The rate of fertilization was significantly higher among GRF-treated females than among controls (74.1 versus 84.7%; P < 0.013). Cytogenetic data were obtained in 262 fertilized oocytes (89 from control females and 173 from GRF treated females). The frequency of aneuploidy, calculated as twice the frequency of hyperhaploidy was 2.31% in GRF-treated females and 2.24% in controls (NS). The use of GRF to treat female mice did not adversely affect the maturation process of oocytes nor did it induce an increased frequency of aneuploidy. PMID- 1291565 TI - The incidence of chromosomal aneuploidy in stimulated and unstimulated (natural) uninseminated human oocytes. AB - The incidence of chromosomal aneuploidy in human oocytes is higher than for various animal species. Since this estimate for aneuploidies is based on data obtained from in-vitro fertilization (IVF) patients, it is possible that superovulation could be contributing to this phenomenon. In this study we determine the incidence of chromosomal aneuploidy in nonstimulated uninseminated human oocytes donated by IVF patients. Furthermore, we compare this incidence of aneuploidy to that obtained after superovulation using two different protocols for induction of multiple follicular growth. The rate of aneuploidy in non stimulated oocytes was 20% (4/20). This is not significantly different from the rate of aneuploidy in oocytes obtained after superovulation with clomiphene/human menopausal gonadotrophin (HMG)/(HCG) (15/43 = 35%, chi 2 = 1.11; P > 0.20), buserelin-flare (8/25 = 32%; chi 2 = 0.32; P > 0.05), and the rate of aneuploidy in the total number of superovulated oocytes (23/68 = 34%; chi 2 = 82; P < 0.30). Furthermore, the incidence of chromosome aneuploidy in non-stimulated uninseminated oocytes (20%) was well within the range and not significantly different from that reported in the literature for both superovulated uninseminated oocytes (range, 21-57%; total aneuploidy rate, 67/216 = 31%; P < 0.30) and superovulated inseminated oocytes (range, 3-56%; total aneuploidy, 339/1480 = 23%; P < 0.95). Consequently, the data provide evidence that superovulation protocols used in IVF may not be responsible for the higher rate of aneuploidy in human oocytes. These results are discussed in relation to hypotheses on the occurrence of meiotic non-disjunction. PMID- 1291566 TI - Effect of human cervical mucus on human sperm motion and hyperactivation in vitro. AB - The aim of our experiment was to examine the effect of exposure to human cervical mucus on quantitative sperm motility with specific reference to hyperactivated sperm motility. Human spermatozoa were allowed to penetrate cervical mucus for 20 min before swimming into Earle's balanced salt solution tissue culture medium for 25 min. The sperm motion characteristics were compared to those which had been obtained from a direct swim-up for 45 min. Spermatozoa treated with mucus were more 'active' than the control group. Multivariate statistical analysis indicated that cervical mucus promotes hyperactivated motility and that sperm sub populations exposed to cervical mucus are very heterogeneous, as indicated by the numbers and motility characteristics of spermatozoa. PMID- 1291567 TI - Influence of sperm parameters on outcome of subzonal insemination in the case of previous IVF failure. off. AB - Subzonal insemination (SUZI) has been proposed for patients with sperm male factor infertility, and in cases of in-vitro fertilization (IVF) failures. However despite SUZI, there still remain couples with very low fertilization rates and even with fertilization failures. Since sperm parameters are known to influence the IVF fertilization rate, we investigated the relation between sperm parameters and the SUZI issue in cases of previous IVF failures with normal or subnormal sperm. Twenty-seven couples were included in the study and were split into two groups according to whether they had normal or subnormal sperm. In the first part of the study a randomized prospective trial comparing SUZI to classic IVF insemination was carried out (11 cycles). In the second part, all the oocytes had SUZI (35 cycles). None of the control inseminated oocytes fertilized. Including all the cases, the fertilization rate after SUZI was 29.8% with a pregnancy rate of 15.2% per cycle. We concluded that: (i) SUZI is efficient for achieving fertilization in cases of IVF failures; (ii) the post SUZI fertilization rate is inversely correlated to the percentage of acrosome defects in the semen (P < 0.001); and (iii) when the sperm is normal, the oocyte quality might be responsible for the previous IVF failures. In spite of a good fertilization rate for this indication, it seems that the chance of having a baby is low. PMID- 1291568 TI - Effects of chamber depth on the motion pattern of human spermatozoa in semen or in capacitating medium. AB - The computer-aided sperm analysis system (CASA) permits precise calculation of the trajectory characteristics of human spermatozoa. Comparison between different chamber depths (10, 20 and 100 microns) revealed variations in the results, which were more evident as the magnitude of the spermatozoon flagellar beat increased. In seminal spermatozoa, the reduced amplitude of movement, linked to the relatively short flagellum and high viscosity of seminal plasma, indicates that the 10 microns-deep chamber can be used for motion analysis without involving extensive modifications. On the other hand, analysis of quicker movement, such as in capacitated spermatozoa, revealed large variations; in particular the proportion of non-progressive hyperactivated spermatozoa was higher in the 20 microns than in the 10 microns chamber (17.9 +/- 14% and 6.9 +/- 4.5% respectively, P < 0.01). In fact the distribution of non-progressive and progressive hyperactivated spermatozoa is depth-dependent. It is therefore necessary to use a chamber of at least 20 microns in depth for sperm analysis in capacitated medium. PMID- 1291569 TI - Propofol anaesthesia for ultrasound guided oocyte retrieval: accumulation of the anaesthetic agent in follicular fluid. AB - Propofol (2,6-diisopropylphenol, Diprivan, ICI-Pharmaceuticals, Manchester, UK) is widely used either as an adjunct in general anaesthesia or as sole anaesthetic agent by the continuous intravenous route and intermittent bolus injections for minor surgical interventions. For several years, we have been using this kind of anaesthesia in transvaginal oocyte retrieval for in-vitro fertilization (IVF), allowing a completely painless puncture on an out-patient basis. From in-vitro studies on mouse oocytes, it appeared that propofol could be deleterious for fertilization in a dose- and time-dependent manner. We therefore investigated the concentrations of propofol in follicular fluid during oocyte retrieval in women. We measured propofol levels in serum and follicular fluid of nine patients at fixed intervals during ultrasound guided oocyte retrieval. Serum levels fluctuated randomly, due to interference from top-off doses of propofol. In follicular fluid, however, we found a steady increase of propofol levels, which was proportional to the total dose of propofol administered. These data indicate that propofol accumulates in follicular fluid. Although it seems unlikely that propofol as used in the present protocol exerts a clinically significant unfavourable effect on IVF, we suggest that the oocyte retrieval procedure should be kept as short as possible, in order to limit the accumulation of the anaesthetic in follicular fluid. PMID- 1291570 TI - Fallopian tube recanalization by selective salpingography: an alternative to more invasive techniques? AB - Selective salpingography was used in a total of 64 patients, engaged in evaluation for infertility and in whom standard hysterograms showed no tubal passage of contrast medium. Fallopian tube catheterization was successful in 92% of the cases; a peritoneal spill of contrast medium was obtained in 74% of the cases by manual injection. Recanalization of an obstructed oviduct was successful in 61% of the cases. Thus, after the procedure, 82% of the patients had at least one patent tube. We conclude that selective tubal catheterization, and recanalization when needed, should be included in the therapeutic procedures for tubal infertility, prior to in-vitro fertilization or tubal microsurgery. PMID- 1291571 TI - Laparoscopic removal of benign mature teratoma. AB - Laparoscopic removal of benign mature teratoma is safe and effective in pre menopausal patients. Fourteen patients underwent laparoscopic removal of such tumours. There were no operative complications. Post-operative hospitalization was short (average: 2 days). All patients undergoing a second-look laparoscopy had mild adhesions around the operated ovary. Two spontaneous and one in-vitro fertilization pregnancy occurred. If a teratoma is diagnosed during laparoscopy or oocyte retrieval, it should be promptly removed as malignant transformation is not excluded. In this case, the embryos should be frozen for later transfer. PMID- 1291572 TI - Diagnostic hysteroscopy: its value in an in-vitro fertilization/embryo transfer unit. AB - A total of 324 patients participating in our in-vitro fertilization/embryo transfer (IVF) programme underwent a diagnostic hysteroscopy. Of these, 152 women were referred before their first IVF attempt, because of some hysterosalpingographic suspicion of an intra-uterine abnormality; the other 172 patients had failed to conceive after IVF and transfer of good quality embryos. An intra-uterine pathology (mainly intra-uterine adhesions) was diagnosed in 50% of the patients in each group. Hysterosalpingography, although very sensitive, had low specificity (23%), a false positive rate of 44% and false negative rate of 10%. The main risk factor for intra-uterine pathology was a previous abortion. Conception rates were 22% after surgical treatment and 38% after the diagnostic procedure. We think that hysteroscopy should be performed in every patient failing to conceive after replacement of good quality embryos. It is also recommended whenever a suspicious finding is revealed by hysterosalpingography, before IVF. Routine hysteroscopy before entering an IVF programme should be seriously considered. PMID- 1291573 TI - Platelet activating factor in culture media as an indicator of human embryonic development after in-vitro fertilization. AB - Although human chorionic gonadotrophin can detect trophoblast after implantation of the conceptus, there is a need to detect the conceptus before implantation. We have investigated whether human embryo-derived platelet activating factor is formed during embryonic development after in-vitro fertilization. A total of 99 ova from 12 patients were cultured and the 54 media were analysed. Platelet activating factor was also measured by radioimmunoassay after extraction. Fertilization increased the amount of platelet activating factor 4-fold over non fertilized ova to a level of 4 ng/ml. This increase was also dependent on the degree of embryonic development with a maximum level of platelet activating factor of 7 ng/ml at the 2-cell stage. The follicular inducing agent used to treat the patient also had an effect on platelet activating factor; buserelin treatment gave embryos with a higher level than did clomiphene citrate treatment. These results indicate that platelet activating factor may have a role in embryonic development before implantation and may serve as a useful marker for fertilization and the developmental stage of the embryo. PMID- 1291574 TI - In vitro maturation of mouse germinal vesicle-stage oocytes following cooling, exposure to cryoprotectants and ultrarapid freezing: limited effect on the morphology of the second meiotic spindle. AB - Cryopreservation of germinal vesicle (GV)-stage mouse oocytes results in a developmental block. As an approach to explain the failure in development, we have investigated the morphology of the second meiotic spindle after in-vitro maturation. Fully grown GV-stage mouse oocytes were collected from the ovaries of primed mice and kept in meiotic arrest with dibutyryl cyclic AMP. These oocytes were submitted to different variables of cryopreservation: (i) cooling to 22 degrees C or 0 degrees C; (ii) exposure to 1.5 M 1,2-propanediol at 22 degrees C or 0 degrees C; (iii) exposure to 1.5 M dimethylsulphoxide (DMSO) at 22 degrees C or 0 degrees C; (iv) ultrarapid freezing with 3.5 M DMSO/0.5 M sucrose; (v) exposure to a sucrose dehydration series according to the ultrarapid freezing protocol. The morphology of the second meiotic spindle was evaluated 16 h after release from meiotic arrest. We were able to demonstrate that following cooling, exposure to cryoprotectants or ultrarapid freezing of GV-stage mouse oocytes, a normal barrel-shaped spindle with the chromosomes in midplane position is found in 79-94% of oocytes except for two conditions with great exposure to dehydration stress. Exposure to DMSO at 0 degrees C or exposure to a sucrose dehydration series resulted in significantly lower percentages of barrel-shaped spindles, respectively 64% and 62%. The effect on spindle morphology has to be put into perspective, however, since the observed abnormalities were changes of spindle shape, such as elongation or reduction, which are assumed to be restorable, and since no polar organizational defects were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291575 TI - Fertilization and embryonic development of human oocytes after cooling. AB - Injury to living cells resulting from rapid cooling to temperatures at or near 0 degrees C has long been recognized, and the phenomenon, which is termed 'cold shock', has been known to occur in some mammalian gametes. Although human embryos have been successfully stored at low temperatures, cryopreservation of the human oocyte is proving to be more difficult. Whether or not this lack of success is a direct result of cellular injury brought about by 'cold shock' is the purpose of the current investigation. Human oocytes were cooled, in the absence of cryoprotectants, at two different cooling rates (-3 degrees C/min and -1000+ degrees C/min) to a temperature of 0 degrees C and rewarmed prior to insemination. In both cases fertilization after cooling was similar to the rates achieved in a routine in-vitro fertilization and embryo transfer procedure. After cooling at -3 degrees C/min, the rate of fertilization was 19/22 (86%) and after cooling at -1000+ degrees C/min, 9/9 (100%), with non-cooled control rates of 62/87 (71%) and 35/50 (70%) respectively. Fertilized oocytes from both groups were successfully cultured for a further 24 h before termination of the experiment. PMID- 1291576 TI - Effects of cryopreservation on survival and development of interphase- and mitotic-stage 1-cell mouse embryos. AB - The effects of cryopreservation with 1,2-propanediol on two groups of 1-cell mouse embryos were studied in terms of survival after thawing, growth in vitro until the blastocyst stage and development in vivo assessed by the number of implantations and living fetuses. The two groups were divided according to different stages in the cell cycle: cells in (i) interphase with two distinct pronuclei or (ii) mitosis just prior to the first cleavage division. Zygotes in the interphase stage proved to be more resistant to freezing and thawing procedures, showing a significantly higher survival rate after thawing than zygotes in mitosis (78.5 versus 61.3%, P < 0.05). Blastocyst formation was similar in the two experimental groups: 72.7% for interphase and 60.8% for mitosis (P = 0.06), but for both groups fewer blastocysts formed when compared with the control group (86.7%) (P < or = 0.01). The implantation rates were not statistically different: 54.2% for the interphase cells and 47.4% for the control group and 44.0% for the mitotic cells and 49.4% for the control group. The formation of living fetuses was similar between the experimental and control groups: 36.5% for the interphase group (40.0% for its control group) and 22.6% for the mitotic group (38.8% for its control group). We conclude that freezing embryos during nuclear division is detrimental for their survival after thawing. PMID- 1291577 TI - Transvaginal intratubal insemination, ectopic pregnancy and treatment by single dose parenteral methotrexate. AB - We report a case of a woman with ectopic pregnancy with fetal cardiac activity after ovulation induction and transvaginal intratubal insemination by tactile sensation. The patient was successfully treated by single-dose methotrexate (MTX) (77 mg or 50 mg/m2 given intramuscularly). Control hysterosalpingograms showed no tubal patency on the involved side. Potential advantages and hazards of transvaginal intratubal insemination and single-dose MTX for ectopic pregnancy are discussed. PMID- 1291578 TI - Immunohistochemical localization of androgen receptor in the human endometrium, decidua, placenta and pathological conditions of the endometrium. AB - The immunohistochemical localization of the androgen receptor in the human endometrium at various stages of the menstrual cycle and post-menopausal period, in decidua and placenta of early pregnancy, and in several pathological conditions of the endometrium has been investigated. At any phase of the menstrual cycle, both endometrial glandular cells and endometrial stromal cells showed positive nuclear staining. Endometrial stromal cells of the functional layer showed stronger staining than those of the basal layer, but endometrial glandular cells of both layers showed the same staining intensity. There was little staining in myometrium. Even after menopause, endometrial glandular and stromal cells showed the same staining pattern as the basal layer of pre menopausal endometrium and the staining intensity of endometrial stromal cells was weak. In decidua and placenta of early pregnancy, decidual and trophoblastic cells showed positive staining and there was no staining in the stromal cells of placenta. The expression of the androgen receptor was also detected in adenomyosis, endometriosis and endometrial carcinoma. Although the proliferation and differentiation of endometrium are mediated mainly by oestrogen and progesterone receptors, the androgen receptor may play some role in modulating these changes. These results suggest that it may be involved in both physiological and pathological changes of the endometrium. PMID- 1291579 TI - Influence of human chorionic gonadotrophin, oestradiol and progesterone on uteroplacental and corpus luteum blood flow in normal early pregnancy. AB - A transvaginal colour and pulsed Doppler study was performed on 44 women with normal pregnancies between 5 and 16 weeks of gestation. Maternal levels of human chorionic gonadotrophin (HCG), free alpha-HCG subunit, free beta-HCG subunit, 17 beta-oestradiol and progesterone were determined in sera obtained at the time of Doppler examination. Uterine peak systolic velocity (PSV) and alpha-HCG and 17 beta-oestradiol levels increased significantly (P < 0.001) from the second to the fourth month of gestation, whereas uterine and spiral resistance index (RI) decreased significantly (P < 0.005 and P < 0.001, respectively) with gestational age. Levels of HCG and beta-HCG peaked significantly (P < 0.01) during the third month of gestation. Corpus luteum PSV and RI and progesterone levels did not vary significantly with gestational age. Multiple regression analysis showed that gestational age was the only significant (P < 0.05) contributor to uterine PSV and spiral RI variability. In addition to gestational age, 17 beta-oestradiol had a significant (P < 0.001) influence on uterine RI. Both corpus luteum PSV and RI were significantly (P < 0.01 and P < 0.05, respectively) related to progesterone levels. Corpus luteum PSV was also significantly (P < 0.05) related to 17 beta oestradiol levels and RI to HCG levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291580 TI - Expression of human chorionic gonadotrophin alpha and beta subunits is depressed in trophoblast from pregnancies with early embryonic failure. AB - The expression of the placental proteins human chorionic gonadotrophin alpha (HCG alpha), beta (HCG beta) and human placental lactogen (HPL) was examined in trophoblast from human normal pregnancy and early embryonic failure (EEF) using Northern blot analysis. Trophoblast from EEF expressed significantly depressed levels of HCG alpha (P < 0.05) and HCG beta (P < 0.01) when compared to normal pregnancy. Levels of expression of HPL in EEF were not significantly different to those from normal pregnancy. The gestational ages of the two groups were not significantly different. Immunocytochemistry on paraffin-fixed tissue sections supported these data and showed that mRNA levels reflected protein production of HCG within the tissue. It appears from these data that the depressed level of HCG found in the serum of women with early pregnancy failure is not solely a consequence of diminished placentation in these pregnancies, or placental necrosis, but that the genes of the alpha and beta HCG subunits are down regulated. This study further suggests that there are two subsets of women with early pregnancy failure; those with apparently normal levels of placental proteins, and those with severely depressed levels. It would seem likely that these two groups have different aetiologies. PMID- 1291581 TI - Recurrent ectopic pregnancy following in-vitro fertilization. PMID- 1291582 TI - Preimplantation genetic diagnosis--a rolling stone gathers no moss! PMID- 1291583 TI - Prospects for the clinical application of preimplantation diagnosis: the tortoise or the hare? PMID- 1291584 TI - Mast cells and basophils: a review of their heterogeneity and function. PMID- 1291585 TI - Critical differences of clinical chemical components in blood from Red Danish dairy cows based on weekly measurements. AB - The critical difference, which may help to judge whether the difference between two consecutive analytical results may be safely ascribed to natural variation or not, was calculated for 12 clinical chemical components determined in blood samples collected once a week for 5 consecutive weeks from 19 clinically healthy Red Danish dairy cows. For each clinical chemical component, the total variance of the analytical results was divided into the component of variance between cows (S2Inter), the component of variance for weeks within cows (S2Intra) and the component of variance for measurements (S2Anal) using nested analysis of variance. The critical difference calculated in absolute values from S2Intra and S2Anal was 0.15 mu kat per 1 for alanine aminotransferase, 0.55 mu kat per 1 for aspartate aminotransferase, 0.57 mu kat per 1 for alkaline phosphatase, 0.14 mu kat per 1 for gamma-glutamyltransferase, 1.95 mu kat per 1 for creatine kinase, 2.23 mmol per 1 for urea, 22 mu mol per 1 for creatinine, 2.4 g per 1 for albumin, 10.0 g per 1 for serum protein Total, 0.71 mmol per 1 for glucose, 0.54 mmol per 1 for calcium and 0.25 mmol per 1 for magnesium. These critical differences may be used as guidelines to evaluate the difference between two consecutive analytical results in cows. However, the analytical results should not be assessed by the critical differences alone, but should also be compared with the corresponding reference intervals. PMID- 1291586 TI - Lenticular lesions in harbour seals (Phoca vitulina). AB - Lenticular lesions were found in 21 of 44 mainly younger harbour seals investigated during the epidemic caused by phocine distemper virus (PDV) in 1988/89. Malformations and cataracts varied in quality and degree and were histologically characterized by proliferative and/or degenerative lenticular alterations. Except for two animals, both eyes were affected symmetrically. For that reason, local exogenous causes are improbable. There was very little evidence for infectious agents isolated from the seals investigated (viruses, in particular PDV, bacteria, mycoplasma, parasites). Environmental, dietary and hereditary aspects were also considered, but no final conclusions could be made as to the involvement of these factors in the genesis of lens lesions in harbour seals. PMID- 1291587 TI - Vacuolar neuronal degeneration in the ventral horns of SCID mice in naturally occurring Theiler's encephalomyelitis. AB - During a spontaneous outbreak of Theiler's encephalomyelitis severe combined immunodeficient mice developed high morbidity and high mortality. Histological lesions were localized in the ventral horns of the spinal cord and brain stem. The salient features were the severe vacuolar degeneration of neurones and glial cells and the absence of inflammatory cellular infiltrates. The clinical and pathological features of this outbreak indicate that the SCID mouse would be a much improved model for studying the mechanism of poliovirus infection and of virus-induced demyelinating diseases. PMID- 1291588 TI - Comparison of four erythrocyte fragility tests as indicators of vitamin E status in adult dogs. AB - Plasma alpha-tocopherol (alpha-T) concentrations, erythrocyte osmotic fragility and detergent sensitivity were measured at 8 week intervals in two 1-year-old male beagle dogs fed a vitamin E-deficient diet (< 0.08 mg per kg alpha-T) and in two control beagles fed the same diet supplemented with vitamin E (> 90 mg per kg alpha-T). Beginning at 24 weeks, dialuric acid haemolysis and spontaneous haemolysis were evaluated also. In the vitamin E-deficient dogs, plasma alpha-T concentrations declined progressively from baseline values of 20.5 and 31.3 micrograms per ml to 0.11 and 0.07 micrograms per ml, respectively, by 90 weeks. The supplemented dogs maintained alpha-T concentrations between 18.3 and 38.4 micrograms per ml. Both dialuric acid haemolysis (R = -0.89) and spontaneous haemolysis (R = -0.91) increased with declining plasma alpha-T concentration. In the dialuric acid haemolysis assay, 50 per cent haemolysis occurred when plasma alpha-T declined to 1.7 micrograms per ml, compared with spontaneous haemolysis in which 50 per cent haemolysis occurred when plasma alpha-T declined to 0.5 micrograms per ml. Osmotic fragility and detergent sensitivity remained unchanged in the vitamin E-deficient dogs throughout the study. Of the four tests, dialuric acid haemolysis was the most sensitive in-vitro assay for vitamin E deficiency in adult dogs. PMID- 1291589 TI - Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study. AB - A spontaneous neurological disease in cats characterized by behavioural and motor disturbances was investigated by clinical, morphological and immunological methods. Neuropathological examination showed a marked inflammatory reaction in the cerebral leptomeninges and the grey matter of the brain. In the white matter, the reaction was moderate. The changes consisted of perivascular cuffing by mononuclear cells and neuronal damage. The brain stem (thalamus, mesencephalon, caudal colliculus) was most severely affected. The spinal cord and its leptomeninges were involved to a lesser degree. The histopathological picture as well as the laboratory findings suggests a viral cause of the disease. The morphology of the disease and serological as well as immunohistochemical results indicate that this disorder is different from previously known feline viral encephalitides. PMID- 1291591 TI - Canine distemper virus infection in a masked palm civet (Paguma larvata). AB - A free-living masked palm civet (Paguma larvata) died after exhibiting signs of canine distemper (CD). The microscopic lesions consisted of cytoplasmic and intranuclear eosinophilic inclusion bodies, bronchointerstitial pneumonia, non purulent encephalitis accompanied by demyelination and lymphocytic depletion in various lymphoid tissues. CD virus-specific antigens were demonstrated immunohistochemically in intracellular eosinophilic inclusions, which were ultrastructurally confirmed to be viral nucleocapsids. From these findings, the present case was diagnosed as CD virus infection in a masked palm civet. PMID- 1291590 TI - An orderly approach to the study of odontogenic tumours in animals. AB - In this paper odontogenic tumours in animals are discussed with the aim of developing a sound basis for further work in this relatively poorly understood field. The following recommendations are made: (1) Odontogenic tumours should be classified according to whether they are of epithelial, mesenchymal or of mixed epithelial and mesenchymal origin, rather than based on inductive changes. (2) The clinical behaviour implied by ameloblastoma, ameloblastic fibroma and odontoma should be carefully considered before these terms are incorporated into the diagnosis of any odontogenic tumour. (3) Caution should be exercised in designating specific odontogenic tumours in animals as being the counterpart of human tumours until their histopathological features and clinical behaviour have been proved to be equivalent. (4) Only tumours that exhibit the typical features of the basal cell layer of ameloblastomas should be designated as ameloblastomas. (5) Ameloblastic epithelium should not be used when odontogenic epithelium is intended. (6) These recommendations should be substantiated by reviewing odontogenic tumours in animals, although doing so will be difficult because of their rarity. PMID- 1291592 TI - Bone histomorphometry in Cushing's syndrome. AB - Bone involvement is a common finding in Cushing's syndrome. The actions of corticosteroids on bone have been studied quite intensively but only a few studies of bone histomorphometry in this syndrome have been published. In this paper we present histomorphometric measurements of bone activity in 7 patients with a postoperative reevaluation in two. The results show irregular alterations on histomorphometric parameters with an increased bone resorption and decreased bone formation rate. After surgery the abnormalities changed towards normal. PMID- 1291594 TI - The value of visual evoked potentials in optic neuropathy of Graves' disease. AB - Visual evoked potentials (VEP) were tested in patients with ophthalmopathy (OP) of Graves' disease (GD) before treatment and half-a-year and 5-7 yr after orbital decompression (7 patients) or retrobulbar irradiation (3 patients). Five patients not requiring treatment for OP and 16 healthy subjects served as controls. Treatment of OP was given on clinical grounds including decreased visual acuity (VA) indicating optic neuropathy. Before treatment VA was decreased in 5 out of 19 eyes whereas VEP were abnormal in all. The mean latency at N60 both in the operated (83.1 +/- 21.6 ms) and in the irradiated groups (80.9 +/- 7.0 ms) was significantly different from that in the untreated group (62.6 +/- 8.2 ms; p < 0.001) and the healthy subjects (58.9 +/- 6.3; p < 0.001). At P120 only the latency of the operated group differed significantly from that of the other groups (p < 0.001). There was a relationship between the eye muscle changes seen on CT scans and the ophthalmopathy score (according to the classification of the American Thyroid Association) and the latency both at N60 and P120. A change from a V-shape to a W-shape of the waves occurred more often in the treated patients before therapy than in the other groups. Two patients had multiphase VEP in both eyes which improved after treatment. After adequate clinical response the visual acuity improved in one of the 5 patients with initially depressed VA. VEP, initially abnormal in all, improved in 7 of the 19 eyes (37%) but further deterioration was observed in 8 (42%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291593 TI - Double-blind controlled trial of progesterone vaginal cream treatment for cyclical mastodynia in women with benign breast disease. AB - The clinical effectiveness and safety of vaginal micronized progesterone treatment in mastodynia were evaluated in a double-blind placebo controlled study. Eighty regularly menstruating women affected by severe cyclical mastodynia were randomly assigned to two groups of 40 patients. One group was treated for 6 cycles from the 19th to the 25th day of the cycle with 4 g of vaginal cream containing 2.5% natural progesterone. The other group was similarly treated with placebo. The treatment was preceded by a control cycle. All patients reported every day their breast pain on a 100 mm visual linear analogue scale (VAS). The response of breast tenderness and nodularity to treatment was assessed by clinical examination. Vaginal progesterone resulted significantly more efficacious than placebo in reducing mean ratings of breast pain on VAS and mean scores of breast tenderness to touch. Success of treatment, defined as reduction greater than 50% of basal mean score of breast pain on VAS, was achieved in the 64.9% of patients treated with progesterone and in the 22.2% of patients receiving placebo (p < 0.01). Conversely, at the end of treatment, the improvement in breast nodularity showed a not statistically significant difference between the two groups. No major side-effects were detected. PMID- 1291595 TI - Time related bias in longitudinal studies using dual photon absorptiometry. AB - Examining the bone mineral density (BMD's) slope of patients regularly followed in our department, we observed recently that the group of patients who had their last BMD during the last 6 months of 1989, had a different slope than patients who had their last BMD during the following 6 months. In order to investigate if a small time-related bias of measurement, unsuspected by the former quality control investigations, could exist, we performed the following analyses. A regression equation between BMD and time was calculated and a slope was obtained for 95 women who had been followed for at least 3 yr and had had at least 3 BMD measurements during that time. The women were divided in 3 groups according to when the last BMD measurement had been performed (July-December 1989, January June 1990 or July-December 1990). The slopes of the 3 groups of patients were compared. For each value of BMD of every patient, a predicted BMD (BMDp) was calculated using the regression equation and the relative difference (RD) between BMDp and BMD was calculated and analysed in relation to time. There was a significant difference (p < 0.05) between the slopes of patients in relation to the time when the last BMD had been measured. Significant fluctuations (p < 0.001) in RD were observed in relation to time. These RD variations suggested the existence of a time-related error. The presence of this error is also substantiated by the fact that a parallelism existed between the curve of the RD variations and the curve of the mean values of BMD of all patients referred to our department, calculated per period of 4 months. Although the fluctuation of the latter curve was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291596 TI - Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women. AB - The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291597 TI - Hormonal and immunological pattern in a patient with acquired immunodeficiency syndrome related complex and Cushing's syndrome. AB - A case of Cushing's syndrome in a 24-yr-old homosexual with an AIDS-related complex is reported. In this patient certain symptoms common to both diseases, i.e. weakness, myalgia and muscle atrophy were accentuated, whereas other symptoms pathognomic of the human immunodeficiency virus (HIV) infection, i.e. lymphoadenopathies and weight loss, were less pronounced by the high levels of circulating adrenal steroids. Ketoconazole was administered po in order to block adrenal steroidogenesis, the drug caused a remarkable fall of cortisol serum concentrations, but was unable to modify significantly the immunological pattern of the patient. Our data suggest that changes of serum adrenal steroid levels have little effect on the immune network of patients with AIDS. PMID- 1291598 TI - Subclinical hypothyroidism, overt thyrotoxicosis and subclinical hypothyroidism: the subsequent phases of thyroid function in a patient chronically treated with amiodarone. AB - In a patient chronically treated with amiodarone, subclinical iodine-induced hypothyroidism occurred as a result of excess iodine released from the amiodarone molecule. The patient was maintained on amiodarone and developed thyrotoxicosis as a result of a destructive process into the thyroid follicles. Amiodarone was withdrawn and methylprednisolone and methimazole treatment was started with resolution of the thyrotoxic phase. Months later, off therapy, the patient developed subclinical hypothyroidism. This is the first description of hypo- and hyperthyroidism in the same patient caused by amiodarone therapy. This unusual observation suggests that patients treated with amiodarone are at risk to develop hyperthyroidism even if they show laboratory findings consistent with hypothyroidism. PMID- 1291600 TI - Caring as everydayness. AB - This article examines caring from an ontological perspective. Believing that the caring practices of nursing are often hidden from view because they constitute the everydayness of practice, it is proposed that one way to reveal caring practices is through storytelling. Brief stories from practice are shared and the author describes how caring practice is embedded within the experience of nursing. PMID- 1291601 TI - Presence: discovering the artistry in relating. AB - Through the substantive practice experience of relating to patients, the author has identified provisional attributes associated with presence. Concept analysis was used to systematically illustrate the uses of presence identified by other authors and disciplines. A model case with the attributes of presence as described by the author is presented. The provisional attributes proposed by the author are (a) time with another (T), (b) unconditional positive regard (UPR), (c) transactional speaking with, being with, doing with (TR), (d) encounter that is valued (EV), (e) connectedness (essence linking) (C), and (f) sustaining memory (SM). The definition of presence as a nursing intervention is included. PMID- 1291599 TI - Insulin resistance due to mutations of the insulin receptor gene: an overview. PMID- 1291602 TI - Energy balancing through touch for health. AB - Through reflection on other types of energy work, the basis is laid for Touch for Health (TFH) as an energetic, touch, body therapy. TFH offers an opportunity for increased awareness of the subtle messages that our bodies are communicating to us. This communication is enhanced through the biofeedback quality of muscle testing. By introducing us to the feeling of well-being that occurs through energy balance, TFH makes individuals more aware of the meaning of optimal-level wellness. It assists people to move to a higher level of self-care. This health maintenance technique can be used anytime, anywhere for ourselves and others. By putting us back in control of our own health and well-being, TFH can increase self-esteem. Applications for nursing practice are explored. PMID- 1291603 TI - Analysis of nurse theorists' definition of health for congruence with holism. AB - This article analyzes the definitions of health of seven nurse theorists for congruence with the American Holistic Nurses' Association's (AHNA) definition of health. The two themes of wholeness and change in the AHNA definition reflect the Fawcett categorization of worldviews as organismic versus mechanistic and change versus persistence. The organismic view assumes the person to be a proactive integrated being; in the change worldview the person is viewed as always in a state of transition and progress in values. All seven theorists' definitions appear to be congruent with the organismic and change focus of the AHNA definition. Clinicians who are seeking a client-focused theory to guide their practice are encouraged to investigate one or more of the nursing theories for adoption. This can have the dual outcome of improving the quality of nursing care and building the knowledge of the discipline as the theories are tested in practice. PMID- 1291604 TI - The development of a conceptual model for multicultural nursing. AB - Cultural diversity exists among all humans, and nurses and patients are no exception to this general phenomenon. The cultural backgrounds of individual nurses and patients are composed of learned norms, values, customs, and beliefs. If nurses are to be as effective as they might in providing holistic nursing care to patients of culturally diverse backgrounds, their technical expertise must be complemented by knowledge of and respect for the various cultures. This is particularly true in situations where nurses are from cultural and ethnic backgrounds different from the patients for whom they are caring. The development of a conceptual model for multicultural nursing practice, based on King's Theory of Goal Attainment, provides direction for both practice and research in nursing and is an essential initial step toward better preparing nurses to provide holistic care in a global society. PMID- 1291605 TI - Standards of practice by Nightingale. AB - Although the American Holistic Nurses' Association (AHNA) has a relatively short history, the ideas and concepts it embodies are similar to those of Florence Nightingale. This article describes those similarities in Nightingales's writings and in the AHNA's philosophy and standards of practice. PMID- 1291606 TI - A clinical research perspective: look to the obvious. AB - The solution to nursing problems can often be found by using a combination of a naturalistic approach and traditional scientific methods. To illustrate this link, the development of a pacifier for low birth weight infants is described. The observation of fetus' thumb sucking in utero led to a broadly based literature review that suggested the idea of the thumb as an appropriate model for nonnutritive sucking. An anthropometric study was conducted to determine if the size of the thumb correlated with the size of the mouth. The correlations between the mouth and thumb further strengthened the appropriateness of the thumb as a model for a low birth weight infant pacifier. PMID- 1291607 TI - Stability of surgical maxillary expansion. AB - Stability after transverse expansion of the maxilla via Le Fort I osteotomy with segments was evaluated in 39 patients. The average expansion was 5.4 mm at the second molars, decreasing almost linearly to 2.8 mm at the first premolars. Postsurgical relapse also was greatest at the second molars, averaging 2.6 mm. The percentage of relapse was greatest posteriorly, decreasing from 49% at the second molars to 30% at the first premolars. Considerable variability in stability followed surgery: Three-fourths of the patients had some relapse at the first molars (greater than 3 mm in 28%), but one fourth were stable. Sixty-two percent of the patients had a net posttreatment gain in arch width at the first molars. No correlation was found between transverse relapse and the type of presurgical orthodontic tooth movement, the use of rigid fixation, or the use of an auxiliary stabilizing arch wire. The amount of postsurgical relapse was significantly greater in those who had concurrent mandibular surgery. To improve clinical results with surgical expansion, we recommend (1) moderate overexpansion at surgery for major transverse changes, (2) maintenance of the occlusal splint for at least 6 weeks, and (3) use of a lingual arch wire or auxiliary labial arch wire to maintain molar width during postsurgical orthodontics. PMID- 1291608 TI - In vitro comparison of screw versus plate fixation in the sagittal split osteotomy. AB - This study evaluated the transverse strength (rigidity) of three groups of sagittal split osteotomies performed in vitro in fresh sheep mandibles. Fixation was accomplished utilizing two different position screw techniques and a monocortical plate technique. Osteotomies fixed with three 2.0-mm screws in an inverted-L pattern and those fixed with one monocortical miniplate were significantly more rigid than those fixed with two 2.7-mm screws placed in a linear pattern. No significant difference in rigidity was noted between the inverted-L group and the miniplate group. PMID- 1291609 TI - Mandibular border movements and masticatory patterns before and after orthognathic surgery. AB - To study the effects of combined surgical-orthodontic treatment, recordings of functional and border movements were obtained before and after surgery for 16 patients with severe skeletal malocclusions. The tracings showed a clear difference in the functional adaptation to mandibular setback and mandibular advancement surgeries. Patients with a skeletal Class III malocclusion who had undergone mandibular setback surgery generally showed an increase in the range of border and masticatory movements postsurgically. Patients with a skeletal Class II malocclusion corrected by mandibular advancement showed a restricted range of motion immediately postoperatively. Even 12 months after surgery, their recordings did not completely approach presurgical values. PMID- 1291610 TI - Temporomandibular joint internal derangements in an orthognathic surgery population. AB - Of a selected group of 39 patients referred for orthognathic surgery, 38 were found to have some stage of internal derangement of the temporomandibular joint prior to surgery, a much higher incidence than previously reported in either symptomatic patients or asymptomatic individuals. Fifteen of 30 patients with follow-up greater than 12 months developed a new arthrosis after orthognathic surgery. All arthroses occurred in previously deranged joints. None of these patients has required joint surgery, but three have experienced pain. Internal derangement may be a contributing factor in the development of dentofacial deformities, and new loading of deranged joints after orthognathic surgery may be a cause of a new arthrosis and skeletal relapse. PMID- 1291611 TI - Harmonic analysis and clustering of facial profiles. AB - The profiles of 83 healthy young adults were traced from right-side photographs, and then digitized with an image analyzer; each profile thus consisted of a series of coordinates. A dedicated computer program using Fourier analysis resulted in an equation of a curve that interpolated all profile points. By means of cluster analysis, profile equations were divided; two clusters each were found for male and female subjects. A mean profile was calculated for each of the clusters, so that four mean profiles were obtained. These profiles were compared with esthetic parameters found in literature; the results showed that the conventional parameters could sometimes give misleading information for orthodontic and craniofacial orthopedic treatment plans. PMID- 1291613 TI - Psychological profiles and motives of adults seeking orthodontic treatment. AB - Personality profiles and the motivations for seeking orthodontic treatment were investigated in a sample of adult patients. An improvement in dental esthetics was found to be the prime motivating factor, and the decision to seek treatment was usually made by the adult patients themselves. Questionnaires to assess personality traits revealed an atypical group of patients demonstrating neurotic traits. These patients were found to have a significantly different perception of their malocclusion than did the "normal" group of adult patients. Patients with neurotic traits may pose problems for clinicians with regard to expectations both during and at the end of treatment. PMID- 1291612 TI - Analysis of 300 dentofacial deformities in Hong Kong. AB - The records of 300 consecutive Chinese patients with a dentofacial deformity were reviewed to determine the spectrum and characteristics of deformities presenting to a university joint orthognathic clinic. Twenty-six percent of the patients had cleft lip and palate with maxillary hypoplasia; within this group, 26% had double jaw deformity and 5% had nasomaxillary hypoplasia. Of the noncleft group, 47% were Class III facial types, of which 59% were due to mandibular hyperplasia. Of the noncleft group, facial asymmetry accounted for 21%, long face for 18%, bimaxillary protrusion for 14%, Class II types for 11%, and short face for 4%. Overall, there was a high incidence of two-jaw deformity, suggesting that severity may be a major factor in the decision by patients to seek treatment. Findings from this study are thought to be generally applicable to overseas Chinese. PMID- 1291614 TI - [Review and outlook on sports dentistry]. PMID- 1291615 TI - [Effects of local anesthetics on healing process of extraction wound in rats with reference to effects of epinephrine]. AB - Effects of local anesthetics on the healing processes of the extraction wound were investigated in the rats. The study was performed on 5 experimental groups: control group (GA), 2% lidocaine without a vasoconstrictor (LEO) and 2% lidocaine with epinephrine 1/20,000 (LE2), 1/80,000 (LE8) and 1/200,000 (LE20). Under general anesthesia (GA) the mandibular 2nd molars were extracted after the injection of each local anesthetic. The control group (GA) had the teeth extracted without a local anesthetic. The wounds were examined histopathologically at timed sequence from 1 day to 14 days after the operation. Postextraction wounds of all the groups healed uncomplicatedly and these 5 groups could be classified into 2 types of healing process: epinephrine-free group (GA and LEO) and epinephrine group (LE2, LE8 and LE20). The 14-day postextraction sockets of the epinephrine-free group were filled with callus, whereas those of the epinephrine group had progressed to the final stage of bony healing unexpectedly. There was no difference in the healing process of each wound in the same group. These results suggest that a local anesthetic without a vasoconstrictor do not modify the postextraction wound healing process, and epinephrine does not prolong but will promote the wound healing. PMID- 1291616 TI - [Studies on reduction of repellent force of rare earth magnets--concerning tooth intrusion]. AB - The purpose of this investigation was to evaluate the sealing effect of the repelling force of the magnets with ferromagnetic stainless steel and also to examine the reduction pattern along with the change of the relative position of the magnets. The Nd-Fe-B magnet as rare earth magnet, and SUSXM 27, YEP-3, SUS 416 as ferromagnetic stainless steel were used in this experiment. The findings were as follows: 1. There was a little decrease of the repelling force of the magnets sealed with ferromagnetic stainless steel. On the other hand, no significant differences in the repelling force sealed with any kind of ferromagnetic stainless steel were found. 2. Direct contact of the repelling force of the phi 4.0 x 1.5 mm magnets sealed with SUSXM 27 of 0.2 mm in thickness was 242 gf. According to relative horizontal 1.2 mm movement keeping direct contact, the vertical and horizontal components of the repelling force were of the same value. 3. The repelling force of the phi 10.0 x 1.8 mm magnets sealed with SUSXM 27 of 0.2 mm in thickness was 815 gf. It showed more than 300 gf of vertical component of the repelling force when the magnets shifted to 3.0 mm horizontally when in contact. 4. It is suggested that the repelling force of the Nd-Fe-B magnets will be clinically useful for the intrusion of molar teeth. PMID- 1291618 TI - [Mechanical response of temporomandibular joint induced by occlusal change]. AB - The purpose of this research was to investigate the mechanical effects on the temporomandibular joint influenced by the occlusal variations: the inclination of the upper incisor and the change of occlusal contacted position on the lower occlusal surface. For this purpose a theoretical study and a model experiment were performed. In the theoretical study, the Rigid Body Spring Model was applied to the temporomandibular joint for analyzation of the stress distribution and movement of the condyle head under the various conditions of the joint. Furthermore, the model experiment could be performed to confirm three dimensionally the findings attained by the theoretical study. The results were as follows: 1. In the phase of the decreasing upper incisor inclination excessively, the direction of the temporomandibular joint force was be rotated counterclockwise and the magnitude of the joint force was be increased. 2. The movement of the condyle head (distance and direction) and the stress distribution of the disk were influenced by the various shapes of the joint and the mechanical properties of the surrounding soft tissues. PMID- 1291617 TI - [Clinical, radiological and histopathological studies of squamous cell carcinoma of lower gingiva]. AB - In order to improve the treatment results of the lower gingival carcinoma, the treatment results were analysed based on the X-ray views, histopathological findings and mode of treatment. A series of 152 cases of primary lower gingival carcinomas treated at the First Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University, during the 25 years between 1964 and 1988 was surveyed. The lesions with the invasive type of bone resorption on the X-ray picture often had unclear tumor margin histopathologically and those of the pressure type had a smooth front, with a small number of exceptions. The five year cumulative survival rate was 76.7% for the pressure type, 64.6% for those without bone resorption, 53.9% for the invasive type. The deeper the resorption was, the higher the death rate was in the invasive type. Grade II of WHO classification and Grade 3 of the mode of invasion had the least recurrence rate and the least frequency of delayed cervical metastases. Grade 4D showed the highest recurrence rate and Grade 4C a high frequency of cervical metastases. Five-year cumulative survival rate was 77.8% for the cases treated by surgery, 65.6% for those by the combination of surgery and radiation, 57.1% for those by chemotherapy and 29.5% for those by radiation. PMID- 1291619 TI - Black nurses in the United States: 1879-1992. AB - In the fall of 1991, while attending the Annual Convention of the New York State Nurses Association, a group of students who had heard me speak at their school recognized me in the audience. One of them blurted out, "That's Dr. Carnegie, the first Black nurse!" I was flattered by the recognition, but not by the designation. True, I have been in this world a long time but not that long. If Mary Mahoney, America's first Black nurse, had been alive in 1991, she would have been nearly 150 years old. This article focuses on the progress made by Black nurses in the 114 years from the time Mary Mahoney graduated from the New England Hospital for Women and Children in Boston, Massachusetts in 1879 to 1992 in the areas of education, employment, and organized nursing. PMID- 1291620 TI - Hypertension management with church-based education: a pilot study. AB - The aim of this pilot study was to evaluate the efficacy of an education intervention for people with hypertension who attended Black churches. The goal was achieved by preparing six registered nurses from six inner city Black churches as educational experts who successfully implemented the intervention at three churches. A sample of 32 subjects from three churches participated in an education intervention on the nature of and management strategies for hypertension. Data were collected before, immediately after, and three months following the intervention. Findings indicate there was a statistical difference in knowledge between pre and post #1 (p = < .001, n = 18) and post #2 (p = < .0001, n = 8) assessments. It was concluded that the educational intervention was effective in increasing knowledge. No significant changes were noted in blood pressure readings and sodium intake. It is questioned whether more than three months are needed to detect meaningful behavioral changes since behavior change is a complex and gradual process. PMID- 1291621 TI - Type A/B behaviors in employed black women: comparison of blood pressures and cholesterol levels. AB - The purpose of this study was to examine the difference in mean blood pressure and mean cholesterol levels between Type A/B employed Black women. Data were collected on age (mean 38.76 years), weight (mean 179.28 pounds), cholesterol (mean 194.45 mg/dL), systolic blood pressures before (mean 130.68 mm Hg), during (mean 138.81 mm Hg), and after (mean 129.98 mm Hg), and diastolic blood pressure before (mean 77.11 mm Hg), during (mean 81.45 mm Hg), and after (mean 76.20 mm Hg) the Type A Structured Interview (SI) on 280 employed Black women. Audio tape analyses of the SI resulted in 136 Type A's and 144 Types B's. Each individual was screened for hypercholesteremia using a portable reflectance photometer. Blood pressure measurements were taken every minute during administration of the SI. The results indicated that Type A's had higher mean systolic blood pressures, higher diastolic blood pressures before, during and after a structured interview, and higher cholesterol levels than Types B's. PMID- 1291622 TI - The recruitment and retention of African American nurses: an analysis of current data. AB - The Recruitment and Retention of African American Nurses: An Analysis of Current Data reviews data collected by the American Nurses Association. During the years 1984-85, 1987-88, and 1990-91, the American Association of Colleges of Nursing, and The National League for Nursing observed trends in minority participation in nursing. Trends regarding African American nurses are emphasized. Data categories analyzed include: (1) registered nurses in practice; (2) admissions, enrollments, and graduations from undergraduate programs of all types; and (3) masters and doctoral enrollment. Detail analysis is performed for African American participation in baccalaureate programs, with a particular focus on the role of nursing programs in historically Black colleges and universities (HBCU). The data demonstrate that there has been growth in the numbers of African American and other minority groups entering nursing and completing undergraduate nursing programs. However, representation is below parity for the minority group's membership in American society. One interesting finding is that HBCUs graduate approximately 25% of African American nurses yearly despite the fact that they enroll less than 3% of the students in baccalaureate programs. The data also suggest a severe underrepresentation of minorities enrolled in masters and doctoral programs [corrected]. PMID- 1291623 TI - Strengthening black and minority community coalitions for health policy action. AB - African Americans and other racial/ethnic minorities suffer greater disparities in health and quality of life than do nonminorities. Health professionals are challenged to improve the health of minority communities by mobilizing minority people to participate in the public policy process through coalition building. The purpose of this article is to examine the role of the nurse in community development and the policy making process. A case study analyzing one nurse's role in community activism for child care policy is presented. Recommendations are provided for strengthening the involvement of minority community coalitions in influencing policy initiatives. PMID- 1291624 TI - Attitudes of nurses toward culturally diverse patients: an examination of the social contact theory. AB - This investigation uses the Social Contact Theory to explore to what extent does level of exposure to culturally different patients affect White nurses attitudes toward these patients. Attitudes and biases of 346 hospital-based nurses toward culturally different patients were measured using a self-administered, Likert type questionnaire titled the Ethnic Attitude Scale. The results of between group t-tests indicated that there were statistically significant differences in biases expressed by White nurses who worked with predominantly African American patients compared to their counterparts who work in a setting with a few African American patients. This study has implications for nursing in education, development, staffing and improvement of the overall quality of nursing care in a global society. PMID- 1291625 TI - Comparative molecular field analysis of CCK-A antagonists using field-fit as an alignment technique. A convenient guide to design new CCK-A ligands. AB - Comparative molecular field analysis (CoMFA) has been used as a three-dimensional quantitative structure-activity relationship (QSAR) method to correlate the affinities of several antagonists towards CCK-A receptors with their steric and electrostatic fields. In this publication, we describe, for the first time, a field-fit operation as an alignment technique. These results could serve as a guide for the design of new non-peptide antagonists. PMID- 1291626 TI - A comparison of progestin and androgen receptor binding using the CoMFA technique. AB - A series of 48 steroids has been studied with the SYBYL QSAR module using Relative Binding Affinities (RBAs) to progesterone and androgen receptors obtained from the literature. Models for the progesterone and androgen data were developed. Both models show regions where sterics and electrostatics correlate to binding affinity but are different for androgen and progesterone which suggests differences possibly important for receptor selectivity. The progesterone model is more predictive than the androgen (predictive r2 of 0.725 vs. 0.545 for progesterone and androgen, respectively). PMID- 1291627 TI - Surface comparisons of some odour molecules: conformational calculations on sandalwood odour V. AB - Molecular surface comparison seems to be a very suitable tool for the investigation of small differences between biologically active and inactive compounds of the same structural type. A fast method for such comparisons, based on volume matching followed by the estimation of comparable surface dots, is presented and applied on a few selected sandalwood odour molecules. PMID- 1291628 TI - LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads. AB - Recent advances in a new method for the de novo design of enzyme inhibitors are reported. A new set of rules to define the possible nonbonded contacts between protein and ligand is presented. This method was derived from published statistical analyses of nonbonded contacts in crystal packings of organic molecules and has been implemented in the recently described computer program LUDI. Moreover, LUDI can now append a new substituent onto an already existing ligand. Applications are reported for the design of inhibitors of HIV protease and dihydrofolate reductase. The results demonstrate that LUDI is indeed capable of designing new ligands with improved binding when compared to the reference compound. PMID- 1291629 TI - A fast and efficient method for 2D and 3D molecular shape description. AB - A new formalism for molecular shape description is described. The formalism, based on considering each molecule as a collection of its 3-atom submolecules, is applied to both the graph theory and geometrical coordinate representations of molecules. The timing results for shape description of several databases indicate that this new method is applicable to large databases. Furthermore, results from clustering a small database show good agreement with clustering results obtained by a distance-matching algorithm. PMID- 1291630 TI - AM1-SM2 and PM3-SM3 parameterized SCF solvation models for free energies in aqueous solution. AB - Two new continuum solvation models have been presented recently, and in this paper they are explained and reviewed in detail with further examples. Solvation Model 2 (AM1-SM2) is based on the Austin Model 1 and Solvation Model 3 (PM3-SM3) on the Parameterized Model 3 semiempirical Hamiltonian. In addition to the incorporation of phosphorus parameters, both of these new models address specific deficiencies in the original Solvation Model 1 (AM1-SM1), viz., (1) more accurate account is taken of the hydrophobic effect of hydrocarbons, (2) assignment of heavy-atom surface tensions is based on the presence or absence of bonded hydrogen atoms, and (3) the treatment of specific hydration-shell water molecules is more consistent. The new models offer considerably improved performance compared to AM1-SM1 for neutral molecules and essentially equivalent performance for ions. The solute charges within the Parameterized Model 3 Hamiltonian limit the utility of PM3-SM3 for compounds containing nitrogen and possibly phosphorus. For other systems both AM1-SM2 and PM3-SM3 give realistic results, but AM1-SM2 in general outperforms PM3-SM3. Key features of the models are discussed with respect to alternative approaches. PMID- 1291631 TI - Faculty openings and recruitment in dental hygiene education. AB - The purpose of this study was to obtain information on the availability of full time teaching positions, job qualifications, and methods of recruitment in dental hygiene education. A questionnaire was mailed in 1990 to 198 dental hygiene program directors to acquire data on faculty positions and recruitment. The initial and follow-up mailings produced an 86% response rate. Data were analyzed using frequency distributions and chi-square analyses. Seventy-seven authorized openings for full-time faculty were reported: 60 were vacancies resulting from the departure of a faculty member. The minimum educational qualification was the baccalaureate degree for faculty positions in associate degree programs, and the master's degree or higher for teaching positions in baccalaureate degree programs. The type of experience required was primarily clinical, although teaching and research were preferred. The majority of positions available were at the entry levels of instructor and assistant professor. The recruitment method reported to be most successful in locating prospective faculty candidates was placement of a notice in a professional journal. PMID- 1291632 TI - Periodontal disease and diabetes mellitus. PMID- 1291633 TI - Evaluating oral lesions. A systematic approach with exercises. PMID- 1291634 TI - Is it ethical to use electronic anesthesia if the procedure is not addressed in your state practice act? PMID- 1291635 TI - Aerosol generation by two ultrasonic scalers and one sonic scaler. A comparative study. AB - The purposes of this study were to compare the amount of aerosols generated from ultrasonic and sonic scalers and to measure the potential depth of respiratory tract penetration. Forty subjects were randomly assigned to receive instrumentation with the magnetostrictive, piezoelectric, or air turbine scaler. The Anderson Air Sampler collected total baseline airborne microbes for 20 minutes prior to treatment and for 20 minutes during instrumentation. This cascade impactor system measures the degree of microbial penetration in a simulated respiratory system. Blood agar plates from the sampler were incubated for 24 hours at 37 degrees C. Colony forming units per cubic foot of air (CFUs/cu. ft.) were enumerated by one blind examiner using a Lab Line Colony Counter. Data for total microbial CFUs/cu.ft. and CFUs/cu.ft. by sampler level were analyzed on the log-transformed data using ANCOVA. Baseline values of airborne bacteria served as the covariate. Results showed no significant difference in mean combined total CFUs/cu.ft. for the magnetostrictive, piezoelectric, or air turbine sonic scalers. The magnetostrictive scaler generated the lowest CFUs/cu.ft. at the deepest level of penetration; however, no significant difference in level of penetration was found among the three scalers. PMID- 1291636 TI - The safe use of fluorides in dental hygiene practice. PMID- 1291637 TI - Effects of vitamin B12-deficiency on testes tissue in rats. AB - The state of vitamin B12-deficiency in rats was evaluated by determination of hepatic vitamin B12-dependent enzyme activities after the animals had fed on a vitamin B12-deficient soybean protein diet for 150 days. The effect of vitamin B12-deficiency on testicular tissue was also studied by morphological observations. Growth of vitamin B12-deficient rats was retarded and marked increase in urinary methylmalonic acid was observed. Vitamin B12 contents in the organs were depressed distinctly by the deficiency, especially in testes, vitamin B12 content decreased to 2.5 ng/g. Hepatic methionine synthase and methylmalonyl CoA mutase activities showed striking depression to 5% of the control rats and extreme vitamin B12-deficiency was confirmed. Testes weight also showed marked decrease together with their relative weight per 100 g body weight. Morphological observations of testes of vitamin B12-deficient rats revealed atrophy of the seminiferous tubules and aplasia of sperms and spermatids. The above results proved that vitamin B12-deficiency affected rat testes, and suggested that the rat could be the animal model for elucidation of the mechanism of B12 action on testicular functions. PMID- 1291639 TI - Effects of cultured milk products by Lactobacillus and Bifidobacterium species on the secretion of bile acids in hepatocytes and in rats. AB - Whey preparations prepared from cultured milk by 19 Lactobacillus (2 species) and 20 Bifidobacterium (5 species) strains were examined for the effects of secretion and synthesis of bile acids in primary cultured rat hepatocytes. The stimulating effect of whey preparation on bile acid secretion depended on the species as well as the strains used for milk fermentation. Two strains belonging to L. casei SBT 2230 (LC2230) and B. longum SBT 2912 (BL2912) produced the whey which stimulates both the secretion of bile acid and the activity of cholesterol 7 alpha hydroxylase, a rate-limiting enzyme for bile acid synthesis. When the cultured products by these two strains were given to rats for 14 days, the products from L. casei (LC2230) were found to stimulate the biliary secretion of bile acids. These results suggest that primary cultured hepatocytes were a useful experimental system as an initial screening for an active principle modulating cholesterol metabolism. PMID- 1291638 TI - Isolation of plasma cholesterol-lowering components from ningyotake (Polyporus confluens) mushroom. AB - The present study was undertaken to isolate component(s) which contributes to the hypocholesterolemic action of Ningyotake (Polyporus confluens) mushroom. The mushroom powder was extracted with 80% ethanol, and the extract and residue were fractionated into five fractions according to the solubility to solvents. When each fraction was added to a diet containing 1% cholesterol and 0.25% sodium cholate and fed to rats, the plasma cholesterol level was significantly decreased only by ethyl acetate-soluble fraction. Therefore, ethyl acetate-soluble fraction was further fractionated by silica gel column chromatography. Two major compounds, which comprised 45.0% and 28.5% of the ethyl acetate-soluble fraction, were obtained in a pure form by the chromatography, and the compounds were identified as grifolin (2-trans, trans-farnesyl-5-methylresorcinol) and neogrifolin (4-trans, trans-farnesyl-5-methylresorcinol), respectively. The addition of grifolin and neogrifolin to the high cholesterol diet was found to lower plasma cholesterol level significantly. PMID- 1291640 TI - Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid metabolism in primary cultured rat hepatocytes. AB - Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5 desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin. PMID- 1291641 TI - Decrease of lactase activity in the small intestine of jejunum-bypassed rats. AB - The effect of jejunum-bypass operation on lactase in rat small intestine was examined. Three groups of four or five rats were designated as jejunum-bypassed, sham-operated and normal rats. All animals including normal rats received by pair feeding 5% glucose/1% NaCl for 5 days following the operation; thereafter they were fed ad libitum the laboratory chow diet. Three weeks after the jejunal bypass operation, the proximal ileum exhibited a hyperplasia as evidenced by a concomitant increase in mucosal contents of both total proteins and DNA. The specific activity of lactase in this segment was significantly lower in the operated rats than sham-operated controls, whereas the specific activity of sucrase in this segment was significantly elevated. The reduction of lactase activity was also evident in the proximal jejunal segment as well as in the distal jejunum which was deprived of luminal nutrition, suggesting that some hormonal factor(s) might be involved in the decrease of lactase activity in jejunum-bypassed animals. Electroimmunoassay revealed that the amount of immunoreactive lactase also declined in the operated rats relative to the sham operated controls. Our results thus suggest that lactase activity in residual ileum is not only unable to compensate for the loss of digestive-absorptive surface of jejunum, but lactase activity even decreases following jejunum-bypass operation. PMID- 1291643 TI - Lipid peroxidation of liposome induced by glucosone. AB - Lipid peroxidation of liposome made of egg lecithin was induced by glucosone (D arabino-hexos-2-ulose), a secondary product of Maillard reaction or glycation of protein. Lipid peroxidation was assessed with measurement of TBARS (thiobarbituric acid reacting substances), POV (peroxide value), and HPLC measurement of MDA (malondialdehyde). EDTA and DTPA (diethylenetriamine pentaacetic acid) inhibited the lipid peroxidation assessed by each method described above, indicating involvement of metal ions. The observed reduction of Fe3+ to Fe2+ by glucosone might be a critical step of the lipid peroxidation. Our findings suggest a possible role of lipid peroxidation of low-density lipoproteins (LDL) induced by glucosone in atherosis caused by diabetes mellitus. PMID- 1291642 TI - An improved high-performance liquid chromatographic assay for the determination of pyridinoline in connective tissues. AB - A high-performance liquid chromatographic (HPLC) method for determination of pyridinoline and its application to connective tissues are described. The chromatographic separation was accomplished by using Inertsil ODS-2 column and a mixture of 0.1 M sodium phosphate and acetonitrile (75:25, v/v) containing sodium dodecyl sulfate (SDS) and ethylenediamine tetraacetic acid (EDTA) as eluent. The chromatogram was developed isocratically and the eluted components were monitored with excitation at 295 nm and emission at 395 nm. The pyridinoline in crude hydrolysate of connective tissues can be determined in 5 min, with as little as 1 pmol of sample. The present method is rapid, simple and can be used for the routine analysis of connective tissues such as cartilage, bone, Achilles tendon and aorta. PMID- 1291645 TI - Correlation between plasma alpha-cysteine proteinase inhibitor level and pyruvate kinase activity in vitamin E-deficient rats. AB - Weaning rats were divided into two groups, one group being fed a vitamin E deficient diet, and the other an alpha-tocopherol-containing (50 mg/kg) control diet. Rats were killed at 1, 2, 3 and 4 months of feeding. The following results were obtained. 1. Both plasma and liver alpha-tocopherol levels decreased greatly by feeding vitamin E-deficient diet for 1 month, and thereafter decreased gradually by continued feeding. 2. Somehow different results were obtained concerning liver peroxidation value by the method of analysis. In the case of chemiluminescence, the value increased by vitamin E deficiency during the first 2 months, but thereafter, the value was almost unchanged. On the contrary, in the case of TBA-RS, the value increased gradually throughout the entire 4 months of feeding period. 3. Both plasma alpha-CPI level and pyruvate kinase activity increased by vitamin E deficiency, showing similar pattern of change with feeding period. Especially, marked increase of these values was observed in vitamin E deficient rats fed for longer than 2 months, and differences from control groups were highly significant (in both cases, at 2 months, p < 0.005, and at 3 and 4 months, p < 0.001). And, in vitamin E-deficient group, including all the rats fed on test diet for 1 to 4 months, correlation between both values was very high, and was highly significant (r = 0.9060, p < 0.001). PMID- 1291644 TI - Inhibitory effect of oligosaccharides derived from plant xyloglucan on intestinal glucose absorption in rat. AB - We studied the effects of oligosaccharides which were obtained from tamarind xyloglucan by cellulase digestion on absorption of 3-O-methyl-D-glucose using the everted sacs from rat small intestine. Among oligosaccharides tested, octasaccharide and nonasaccharide, which contain D-galactose residue at non reducing terminals, inhibited effectively absorption of 3-O-methyl-D-glucose, and their inhibitory effects were concentration-dependent. On the other hand, heptasaccharide not having D-galactose residue at its non-reducing terminal showed no inhibitory effect on absorption of 3-O-methyl-D-glucose. These results indicate that the octasaccharide and nonasaccharide may not only serve as a soluble dietary fiber with small molecular weight but also lower the blood sugar level. PMID- 1291646 TI - The kidney as a sensor: functional evidence. AB - PURPOSE: To evaluate the effects of afferent renal nerve activity on reflex control of the cardiovascular system and volume balance. ANATOMICAL AND ELECTROPHYSIOLOGICAL EVIDENCE: In the kidney, receptors sensitive to mechanical and chemical stimuli have been identified. Afferent fibres from the kidney have been shown to travel along renal nerves and dorsal roots, mainly from T9 to L4, and to project to the central nervous system at spinal and supraspinal levels. Most of the brainstem regions involved in cardiovascular control and several regions of the anterior hypothalamus (including vasopressin-secreting neurons) receive inputs from renal afferents. REFLEX EFFECTS ON THE CARDIOVASCULAR SYSTEM: The electrical stimulation of afferent renal nerve fibres can either increase or decrease systemic arterial pressure. The hypertensive response to electrical stimulation of renal afferents is the result of widespread activation of the sympathetic nervous system, leading to an increase in peripheral vascular resistance. Activation of afferent renal nerve fibres by an intrarenal artery infusion of adenosine elicits sustained increases in arterial pressure, heart rate and cardiac output without changing total peripheral resistance, indicating reflex activation of the sympathetic nervous system, predominantly restricted to the heart. An increase in the plasma vasopressin concentration, observed during the electrical stimulation of renal afferents, might help to mediate the hypertensive response to afferent renal nerve stimulation. RENORENAL REFLEXES: The existence of neural renorenal reflexes, by which one kidney can influence the functioning of the opposite kidney, is well established. Contralateral renorenal reflexes, which are inhibitory in nature, are tonically active and mainly control the secretion of renin from juxtaglomerular cells and the tubular reabsorption of sodium and water. CONCLUSIONS: The evidence suggests that sensory information from the kidney contributes to the overall regulation of cardiovascular homeostasis and volume balance. PMID- 1291647 TI - Peptides as targets for antihypertensive drug development. AB - AIM: To assess the potential for development of new classes of pharmacological drugs in the treatment of hypertension and cardiovascular disease. BACKGROUND: Basis of pharmacological blood pressure reduction: Since the discovery of the renin-angiotensin system by Tigerstedt almost 100 years ago, a large number of vasoactive peptides have been discovered. By interaction with such peptides of endocrine, perivascular or endothelial origin, blood pressure may be modulated. BLOCKADE OF THE RENIN-ANGIOTENSIN SYSTEM: The success of the angiotensin converting enzyme (ACE) inhibitors in hypertension and congestive heart failure is generally attributed to reduced generation of angiotensin II. The recent development of specific and highly potent Ang II type 1 subtype receptor antagonists such as losartan (DuP753, MK954) have provided a new opportunity to inhibit the renin-angiotensin system, and this is currently being explored in hypertensive patients. In addition, blockade of the first and rate-limiting reaction of the renin-angiotensin system, inhibition of renin activity, is also a target for the development of antihypertensive drugs. However, this development is hampered at present by a compensatory increase in active renin that clinically offsets the antihypertensive action of renin inhibitors. PHARMACOLOGICALLY INDUCED INCREASE IN ATRIAL NATRIURETIC PEPTIDE (ANP): The availability of circulating or tissue ANP may be increased by inhibiting its metabolic clearance by NEP-24.11 inhibitor drugs. These agents induce a reduction in blood pressure and diuretic effects in animal models, and may become a new class of drugs for the clinical management of patients with hypertension and congestive heart failure. OTHER POTENTIAL PHARMACOLOGICAL TARGETS IN THE MANAGEMENT OF HYPERTENSION: There are several potential pharmacological targets that may lead to the development of novel antihypertensive agents in the future. These include the interaction or blockade of vasopressor peptides. Routes of development include neuropeptide Y1 receptor antagonists, which block the postjunctional vasopressor effect of neuropeptide Y, or endothelin antagonists, which block endothelin pressor actions at the endothelin A receptor site. The cardiovascular actions of the functional neuropeptide Y inhibitor alpha-trinositol (PP 56) provide a potential new mechanism for reducing blood pressure in hypertension. In addition, the recent discovery of small molecular agents with high potency and specificity for the endothelin A receptor subtype may also be of value in specific vascular disease states. CONCLUSIONS: Future development is likely to provide us with novel drugs based on interactions with vasoactive peptides that may improve the management of specific cardiovascular disease states. PMID- 1291648 TI - Adrenergic receptors and their signal transduction mechanisms in hypertension. AB - BACKGROUND: Recent years have witnessed an astonishing proliferation in the number of known adrenoceptor subtypes and related signaling pathways, all of which can potentially be altered in hypertension. Although numerous reports have suggested altered adrenoceptors, guanine nucleotide binding regulatory proteins (G proteins) or effector mechanisms in hypertensive animals or patients, only few clear trends have emerged. CARDIAC AND VASCULAR ADRENOCEPTOR FUNCTION: Cardiac beta-adrenoceptor function is desensitized in various forms of hypertension but it is not clear whether alterations in signaling contribute to this desensitization in addition to the well documented decrease in beta 1 adrenoceptor numbers. Vascular alpha- and beta-adrenoceptor responsiveness are increased and decreased, respectively, in hypertensive animals and patients but the molecular site underlying these alterations has not unequivocally been established. RENAL ADRENOCEPTOR FUNCTION: Renal alpha 1- and alpha 2B adrenoceptor numbers are frequently increased in genetically hypertensive rats but alpha 1-adrenoceptor-stimulated inositol phosphate formation is unchanged or decreased and alpha 2-adrenoceptor functions remain unclear. Renal beta adrenoceptor numbers are elevated in many forms of hypertension but it is not clear whether this is accompanied by alterations in receptor function. PMID- 1291649 TI - The microcirculation and hypertension. AB - AIM: To review published evidence on the effects of arteriolar changes in primary and secondary hypertension. BACKGROUND: Pressure profile analyses have shown that the microcirculation is a major site of vascular resistance. With the recent refinement of intravital microscopy techniques detailed information has become available on mechanisms of the microvascular resistance increase in hypertension. Three mechanisms play an important role: (1) a decrease in arteriolar diameter; (2) arteriolar vessel wall hypertrophy; and (3) small arteriolar and capillary rarefaction. METHOD: The evidence was synthesized into a hypothesis on the role of the microcirculation in primary forms of hypertension. HYPOTHESIS: The hypothesis formulated contains two important elements in that (1) diminished outgrowth of the microvascular bed in different tissues is seen as an important early pathogenic mechanism; and (2) the decreases in arteriolar diameter and vessel wall hypertrophy are seen as adaptive mechanisms that maintain a constant wall stress. The three factors together maintain the increase in vascular resistance that is common to all established forms of primary hypertension. PMID- 1291650 TI - Renin inhibitors, angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists: relationships between blood pressure responses and effects on the renin-angiotensin system. AB - AIM: To compare the effects of angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II (Ang II) antagonists. METHOD: Survey of data from recent studies. DISCREPANCY BETWEEN BLOOD PRESSURE REDUCTION INDUCED BY ACE INHIBITORS AND PLASMA ANG II LEVELS: Studies on the effects of ACE inhibition in hypertensive subjects have suggested that with chronic ACE inhibitor treatment, blood pressure remains lowered even when plasma Ang II returns to normal. However, this discrepancy may be largely an artefact related to difficulties in measuring low Ang II levels in the presence of high angiotensin I (Ang I) levels. Even with modern sensitive and specific Ang II assays it can be difficult to monitor in vivo ACE inhibition (Ang II:I ratio in plasma) because of ex vivo Ang II formation. Recently, in measuring 24-h blood pressure responses to ACE inhibitor treatment, we have obtained good correlations between the time-course of the blood pressure response and the change in circulating Ang II. PROBLEMS IN MEASURING RENIN ACTIVITY: Routine assays of renin activity in plasma can lead to an overestimate of the degree of in vivo inhibition during renin inhibitor treatment, because some protease inhibitors that are used in these assays can cause an ex vivo displacement of protein-bound renin inhibitor, thereby increasing its free concentration. This must be taken into account when using the ratio of enzymatically active renin to immunoreactive renin as an index of in vivo renin inhibition. BLOOD PRESSURE RESPONSE AND ANG II LEVELS WITH RENIN INHIBITORS AND ANG II ANTAGONISTS: Results published so far seem to indicate that with these drugs, as with the ACE inhibitors, the magnitude of the blood pressure effect is correlated with the decrease in the 'effective' Ang II concentration at the receptor sites. However, the time-course of the two effects may be different; with the renin inhibitors, the maximum effect on pressure was delayed compared with the effect on Ang II. CONCLUSIONS: Further studies are needed to establish the exact time-course of renin and Ang II changes and their relationship to blood pressure. Only with rigorously controlled assays will it be possible to answer the question whether, for a given change in 'effective' Ang II concentration at the receptor sites, the effect on blood pressure is different with the three classes of anti-renin-angiotensin drugs. PMID- 1291651 TI - Deficient production of nitric oxide induces volume-dependent hypertension. AB - AIM: To study the influence of nitric oxide on renal function. DESIGN: Nitric oxide synthesis was inhibited and the effects on renal parameters were determined. METHODS: Nitric oxide synthesis was progressively blocked by the intravenous administration of increasing doses of NG-nitro-arginine methylester (L-NAME) and then (c)GMP was administered. RESULTS: The blockade of nitric oxide synthesis first induced a marked fall in urinary sodium excretion, and later, a sustained increase in mean arterial pressure. These effects were reversed by 8 bromide cGMP. Nitric oxide-dependent cGMP formation was higher in the inner medulla than in any other part of the renal parenchyma, and the inhibition of nitric oxide synthesis significantly decreased both pressure- and volume expansion-induced natriuresis. CONCLUSIONS: Both the natriuretic and vasodilator tone maintained by nitric oxide are ultimately due to the production of cGMP. Nitric oxide-induced formation of cGMP appears to be the major factor that links changes in renal medullary circulation to those of sodium excretion. Sufficient inhibition of nitric oxide synthesis to decrease sodium excretion without altering blood pressure induces volume-dependent hypertension because blood pressure is elevated by an increased sodium intake. PMID- 1291652 TI - Interpretation of the acetylcholine test of endothelial cell dysfunction in hypertension. AB - BACKGROUND: In the hypertensive circulation, endothelial cells may release less nitric oxide or more endothelin-1, both powerful vasoactive substances, suggesting an attractive hypothesis for the initiation or reinforcement of hypertension. These substances, however, are not the only way that endothelial dysfunction could be involved in hypertension. In this work we examine the role of the endothelium as a diffusion barrier to vasoconstrictor substances, as a metabolic barrier and as a secretory source of paracrine hormones. REVIEW OF DATA: The evidence that endothelial cell dysfunction occurs in different forms of hypertension comes mainly from the loss of relaxation revealed by the 'acetylcholine test' in a variety of preparations. We examined the strength of this evidence in terms of the stability of the agonist, equilibrium between agonist and receptor, and variations in acetylcholine and other receptor populations on endothelial and smooth muscle cells. The range (Emax) and sensitivity (EC50) of the acetylcholine test was considered in a novel approach to determine the full range by in vitro assay. Using conscious rabbits, we showed that the vascular amplifier of resistance in the hypertensive bed can lead to misinterpretation of changes in reactivity. CONCLUSION: The question of endothelial dysfunction in hypertension as determined by the acetylcholine test is far from proven. PMID- 1291653 TI - Effect of renal medullary circulation on arterial pressure. AB - PRESSURE-NATRIURESIS EFFECTS IN HYPERTENSION: Considerable advances have been made in our understanding of pressure-natriuresis and the effects of this mechanism in hypertension. We have shown that in the absence of changes in neural and endocrine factors, sodium and water excretion doubled when arterial pressure was increased by only 10 mmHg. These responses were greatly blunted or obscured by elevations in renal sympathetic tone, infusion of the vasoconstrictors angiotensin and vasopressin or by inhibition of paracrine factors such as eicosanoids and nitric oxide. EFFECT OF CHANGES ON MEDULLARY BLOOD FLOW: The pressure-natriuresis response is closely associated with changes in papillary blood flow as determined by laser-Doppler flowmetry. In volume-expanded rats, papillary blood flow is not well autoregulated, which results in elevations of vasa recta capillary pressure and renal interstitial fluid pressure. The increased interstitial fluid pressure is transmitted from the medulla to the cortex in the encapsulated organ and is associated with inhibition of sodium transport in the proximal tubule and/or the thin descending loop of Henle of deep nephrons. Selective reductions in medullary blood flow by infusion of the nitric oxide inhibitor N6-nitro-L-arginine methylester (L-NAME) into the renal medullary interstitial space resulted in decreased interstitial fluid pressure and reduced sodium excretion. The mechanisms by which small elevations in renal interstitial fluid pressure alter tubular sodium reabsorption remain to be determined. PRESSURE-NATRIURESIS EFFECTS IN HYPERTENSIVE RATS: Our studies have also shown that the pressure-natriuresis response is blunted in spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. This abnormality is associated with shifts in the relationships among papillary flow, renal interstitial pressure and renal perfusion pressure towards higher pressures. The calcium antagonist nisoldipine corrected the defect in vasa recta hemodynamics in SHR and normalized relationships among sodium excretion, renal interstitial pressure and renal perfusion pressure. CONCLUSIONS: These studies indicate that sodium and water excretion is very sensitive to small changes in renal perfusion pressure due to associated changes in papillary blood flow, and that alterations in medullary hemodynamics can have an important effect on the relationship between arterial pressure and sodium and water excretion. PMID- 1291654 TI - Obesity and hypertension: experimental data. AB - BACKGROUND TO DATA REVIEW: Epidemiologic surveys have demonstrated that hypertension is associated with obesity in a substantial proportion of cases, particularly in young and middle-aged adults. Despite the clinical importance of this association the nature of the relationship between body weight and blood pressure remains obscure. CONCLUSION OF DATA REVIEW: The data reviewed here indicate that obesity-related hypertension involves insulin and the sympathetic nervous system, and may be part of a metabolic adaptation to the obese state. PMID- 1291655 TI - The fetal origins of adult hypertension. AB - AIM: To elucidate the fetal origins of hypertension. METHODS: A systematic search was made for records of early growth, comprising measurements taken either at birth and/or during infancy, for groups of men and women now in middle-late life. Over 25,000 men and women born before 1931 were successfully traced. RESULTS: Retarded growth in fetal life was strongly related to high blood pressure in adult life. CONCLUSION: Hypertension is programmed by an adverse environment in utero. It is linked to impaired development in both early and late gestation. PMID- 1291656 TI - Aging, blood pressure and mortality. AB - POPULATION STUDIES: We reviewed population studies that relate mortality to blood pressure in the elderly. A positive relationship between blood pressure and mortality at the age of 60-69 years was weaker over the age of 75 and became a negative relationship over the age of 85, with hypertensive subjects living longer. This negative relationship probably reflects cardiac, respiratory and neoplastic disease in very elderly subjects with low blood pressure. Therefore, in very elderly hypertensive subjects we cannot conclude that a reduction in blood pressure will not be beneficial, for example in reducing stroke events. CLINICAL TRIALS: The results of clinical trials of antihypertensive treatment in the elderly provide inadequate evidence to assess the benefit of treating hypertensive subjects over the age of 80 years. A randomly allocated controlled trial is required in this age group. PMID- 1291657 TI - Advances in the community control of hypertension: from epidemiology to primary care practice. AB - PURPOSE: To review the progress in hypertension control in the United States since 1972, to examine the factors that contributed to that progress and to consider areas in which further improvement is required. METHODS: A review of epidemiological, clinical and health services research related to hypertension control was conducted. We report our experience in evaluating hypertension control in a multi-ethnic community clinic population as an illustration of the challenges of hypertension management in primary care practice. SUMMARY OF FINDINGS: Hypertension prevalence in the United States population has remained relatively stable, whereas actual blood pressure levels in the population have declined slightly. Most Americans (approximately 80%) have had a blood pressure check within the past year, but the rate of blood pressure control in treated hypertensives has been disappointing. The current diagnostic and therapeutic criterion of blood pressure < or = 140/90 mmHg, regardless of individual patient characteristics (e.g. age, race), should be re-evaluated. PMID- 1291658 TI - Blood pressure disturbance in diabetes mellitus. AB - BACKGROUND: Arterial hypertension and, less often, postural hypotension are frequently associated with diabetes mellitus, and with diabetic complications and death. AIM: To review data on the relationship between hypertension and nephropathy in diabetes mellitus. METHODS: We reviewed data on both retinopathy and nephropathy in hypertensive diabetic patients. Data suggesting that vasopressin levels might affect blood pressure in upright patients with postural hypotension due to cardiocirculatory diabetic neuropathy were also examined. Antihypertensive treatment during different phases of diabetic nephropathy in insulin-dependent diabetes was reviewed. RESULTS: The data showed that hydrochlorothiazide and nitrendipine reduce urinary protein excretion in parallel with a reduction in blood pressure. However, the decreases in urinary protein excretion induced by captopril are not correlated with a reduction in blood pressure and may be related to decreases in intraglomerular pressure found in patients with mild renal failure taking furosemide. Domperidone, a peripherally acting dopaminergic antagonist is an additional therapeutic option for the treatment of diabetic postural hypotension. PMID- 1291659 TI - Cerebral vascular changes during chronic hypertension: good guys and bad guys. AB - AIM: To examine new concepts concerning structural changes in cerebral blood vessels during chronic hypertension, and to examine mechanisms that lead to cerebral vascular complications, in light of the hypothesis that hypertensive vascular hypertrophy may be harmful. METHOD: Literature review. RESULTS: The evidence suggests that the current view is not correct in relation to the cerebral circulation. Vascular hypertrophy and remodeling appear to protect cerebral vessels during hypertension, instead of being harmful. Major cerebral vascular complications during hypertension may be largely due to endothelial dysfunction. One function of the cerebral endothelium is to serve as the blood brain barrier. Disruption of the blood-brain barrier appears to mediate hypertensive encephalopathy. A second endothelial function is to modulate vascular tone. Abnormalities in vasoactive factors that are released by the endothelium (impaired vasodilator mechanisms and augmented vasoconstrictor mechanisms) may make an important contribution to the pathophysiology of transient ischemic episodes, and perhaps stroke, in chronic hypertension. PMID- 1291660 TI - Epidemiology and prevention of blood pressure-related renal disease. AB - AIM: To examine the relationship between blood pressure and end-stage renal disease. METHOD: Review of recent reports on blood pressure in relation to renal function. BACKGROUND: The incidence and prevalence of treated end-stage renal disease are increasing progressively in economically developed countries. To combat this problem, the treatment of established end-stage renal disease must be complemented by strategies to treat and prevent risk factors for the development of renal failure. RESULTS: Severe hypertension and malignant hypertension are well accepted as risk factors for renal insufficiency. Recent reports suggest a strong relationship between blood pressure and renal function, throughout the entire range of blood pressure. Most blood pressure-related renal disease can probably be attributed to mild hypertension or a high normal blood pressure. CONCLUSIONS: Additional clinical trials are needed to assess the value of different antihypertensive drugs and different levels of blood pressure control in preserving renal function in subjects at risk of blood pressure-related renal disease. Primary prevention of hypertension may be an important complement to the treatment of established hypertension in reducing the burden of renal disease in the community. PMID- 1291661 TI - Renal consequences of arterial hypertension. AB - AIM: To seek ways of improving the prognosis for renal function in the presence of arterial hypertension. BACKGROUND: Nephrosclerosis is a term used to define the renal damage induced by arterial hypertension. The renal vasculature can participate in the genesis of essential hypertension and can suffer the consequences of elevated blood pressure. There is no doubt that antihypertensive therapy has dramatically improved the prognosis for renal function in the presence of arterial hypertension. RESULTS OF LITERATURE REVIEW: There appears to be a need for a further improvement in the prognosis for renal hypertension. At present, the prevalence of nephrosclerosis as a cause of terminal renal failure may be increasing and a progressive fall in renal function in treated hypertensive patients compared to normotensives has been described. CONCLUSIONS: It is not yet clear whether improvements in renal hypertension depend merely on the effectiveness of antihypertensive therapy in reducing arterial blood pressure or whether it will be necessary to improve the metabolic disturbances that accompany hypertension or the renal hemodynamic effects of different drugs before the prognosis for nephrosclerosis can be improved. PMID- 1291662 TI - Glomerular hypertension: cause and consequence of renal injury. AB - BACKGROUND: Glomerular capillary hyperfiltration and hypertension occur in certain disease states and also in response to a reduction in the number of functional nephrons. Experimental studies have shown that these glomerular hemodynamic changes are maladaptive, and ultimately damaging to the kidney. Amelioration of glomerular hyperfunction by dietary protein restriction or antihypertensive therapy lessens glomerular injury in several experimental models of chronic renal disease. THESIS: Hyperfiltration may similarly occur in humans with diabetes mellitus, a solitary or remnant kidney, or acquired renal disease. There is evidence to suggest that these people may therefore be at increased risk for the development of renal injury. CURRENT RESEARCH: Clinical studies have shown that dietary protein restriction and antihypertensive therapy may beneficially affect the course of chronic renal failure in humans. Large multicenter trials are currently underway on the effects of these therapeutic maneuvers on the progression of chronic renal disease. PMID- 1291663 TI - Business planning for all seasons. PMID- 1291664 TI - The problem denture patient. Reflections. PMID- 1291665 TI - Defining successful treatment of temporomandibular disorders. PMID- 1291666 TI - Community service day '92. PMID- 1291667 TI - Oral inflammatory diseases and the toothbrush. PMID- 1291668 TI - Twelve ways to improve collections. PMID- 1291669 TI - A rationale for the parallel intraoral radiographic technique. PMID- 1291670 TI - A discussion of alveolar bone physiology relative to implants for the elderly. PMID- 1291671 TI - OSHA's bloodborne pathogen rule what is the role of the dentist? PMID- 1291672 TI - Children at risk: latex allergy and spina bifida. AB - A collaborative study conducted by nurse coordinators at five centers for children with spina bifida (myelodysplasia) identifies the increased incidence of allergies to latex products--gloves, balloons, and catheters--in this population. Reports from 185 families or adult patients with spina bifida on a questionnaire developed by the nurse coordinators describe the sample characteristics and history to allergies. Statistical analysis concludes that children with spina bifida have a higher incidence of allergies to latex products at 20.4% than the controls at 1.1%. Patient age and the presence of shunted hydrocephalus also correlated positively with latex allergy. The increased risk in this population for latex allergy and the life-threatening reactions (anaphylaxis) have implications for patient, family, and professional education. PMID- 1291673 TI - Effects of the nursing Mutual Participation Model of Care on parental stress in the pediatric intensive care unit--a replication. AB - The pediatric intensive care unit (PICU) hospitalization of a child is stressful for parents. Helping parents to decrease their stress is warranted so that they can function in a vital role that is therapeutic to them and their critically ill child. Although many interventions have been recommended to help parents decrease their stress, only the Nursing Mutual Participation Model of Care (NMPMC) has been tested in the clinical setting. This article reports a study that expands on Curley's original work by investigating the effects of the NMPMC on parental stress when implemented by PICU staff nurses. Fifty-six parents participated in the study, which used a quasi-experimental design. Sequential sampling placed the first 31 subjects into the control group and the next 25 subjects in the experimental group. The experimental group received care from staff nurses instructed in the NMPMC. The dependent measure was the Parental Stressor Scale:Pediatric Intensive Care Unit (PSS:PICU) administered within 24 to 48 hours of PICU admission, every 48 hours thereafter, and 24 hours after PICU discharge. The results indicated that parents in the experimental group perceived less stress than the control group, specifically the stress related to alterations in parental role in the PICU setting. Implications for nursing care are discussed. PMID- 1291674 TI - On the nature of social support for families of critically ill children. AB - The purpose of this study was to explore the nature of family social support during an acute life-threatening health crisis of a child. A convenience sample of 10 families was obtained from two pediatric intensive care units (PICUs) in a major midwestern metropolitan area. Tape-recorded interviews of parents took place in the hospital 2 to 13 days after admission to the PICU. The Family Crisis Support Interview (FCSI) was developed from existing literature on social support with content selected for specificity to this population. Qualitative analysis was used to reduce verbatim interview transcription data into four major categories with related themes. Results suggest that for these families (a) costs of support received sometimes outweighed the perceived benefits; (b) the benefit of the social network to parents was influenced by its density and level of connectedness; (c) mothers received more network support than fathers; and (d) dyadic cohesion was a central factor in perceptions of overall support. Interpretation of the data include general applications to family nursing management in pediatric critical care. PMID- 1291675 TI - A case illustration of family management style. AB - Chronic illness management is a way of life for many children and their families. For these chronically ill children, the ability of the family to respond to the daily relentless demands of management dictates the quality of the child's and family's life. In an effort to better understand how a family responds to a chronic illness, Knafl and Deatrick's Family Management Style (FMS) model is applied to a family with a child with type I diabetes using a case-study analysis. Gallo derived dimensions of the model's components in an earlier application. These dimensions are applied to interview data obtained on the same family 1 year later to address the dynamic nature of family management style. PMID- 1291676 TI - Strategies for consoling the infant with colic: fact or fiction? AB - "Persistent" crying has been labeled a developmental crises of parenthood, given the feelings of inadequacy it engenders in new parents. Nearly one of five infants has colic, or more than 700,000 infants in the United States each year. Because there is no "cure" for colic, therapeutic approaches are generally aimed at "containment" of the crying. Such approaches can be classified as feeding/formula modifications, pharmacological agents, and sensory stimulation approaches. This report examines the evidence supporting or refuting the utility of each approach. PMID- 1291677 TI - Poverty: its effects on children and their families. PMID- 1291678 TI - Rice-based oral rehydration fluid in the treatment of infant diarrhea. PMID- 1291679 TI - Establishing a Writer's Academy. PMID- 1291680 TI - Pediatric nursing in Switzerland. PMID- 1291681 TI - A patch-clamp study of the Ca2+ mobilization from internal stores in bovine aortic endothelial cells. I. Effects of caffeine on intracellular Ca2+ stores. AB - The effects of agents known to interfere with Ca2+ release processes of endoplasmic reticulum were investigated in bradykinin (BK)-stimulated bovine aortic endothelial cells (BAE cells), via the activation of Ca(2+)-activated potassium channels [K(Ca2+) channels]. In cell-attached patch experiments, the external application of caffeine (1 mM) caused a brief activation of K(Ca2+) channels in Ca(2+)-free and Ca(2+)-containing external solutions. The application of BK (10 nM) during cell stimulation by caffeine (1-20 mM) invariably led to a drastic channel activation which was maintained during a recording period longer than that observed in caffeine-free conditions. In addition, the cell exposure to caffeine (20 mM) during the BK stimulation enhanced systematically the channel activation process. Since a rapid inhibition of BK-evoked channel activity was also produced by removing caffeine from the bath medium, it is proposed that the sustained single-channel response recorded in the concomitant presence of both agents was due to their synergic action on internal stores and/or the external Ca2+ entry pathway resulting in an increased [Ca2+]i. In addition, the local anesthetic, procaine, depressed the initial BK-induced K(Ca2+) channel activity and completely blocked the secondary phase of the channel activation process related to the external Ca2+ influx into stimulated cells. In contrast, this blocking effect of procaine was not observed on the initial caffeine-elicited channel activity and could not suppress the external Ca(2+)-dependent phase of this channel activation process. Our results confirm the existence of at least two pharmacologically distinct types of Ca(2+)-release from internal stores in BAE cells: an inositol 1,4,5-triphosphate (InsP3)-dependent and a caffeine induced Ca(2+)-release process. PMID- 1291684 TI - Blindness in the world: nursing experience in Nepal. AB - According to statistical data from the World Health Organization, 41 to 52 million people have a vision of 20/200 (6/60) or less; 85% of these blind live in Asia and Africa. Cataract is the leading cause of blindness in underdeveloped countries. Glaucoma and infections are the other main causes. Half of the blind could be helped by surgery and 25% of blindness could be prevented. Strategies for prevention of blindness include an accurate estimation of the number of blind, an evaluation of the main causes of blindness, and behavioral changes in hygiene, nutrition, and seeking eye care. Although Nepal is one of the poorest countries in the world, their eye care system is well-organized. The ophthalmic assistants constitute the backbone of the prevention program. They are trained to screen for diseases, give primary eye care, and assist in surgery. PMID- 1291682 TI - A patch-clamp study of the Ca2+ mobilization from internal stores in bovine aortic endothelial cells. II. Effects of thapsigargin on the cellular Ca2+ homeostasis. AB - Evidence was provided, in the preceding paper (Thuringer & Sauve, 1992), that the external Ca(2+)-dependent phase of the Ca2+ signals evoked by bradykinin (BK) or caffeine in bovine aortic endothelial cells (BAE), differ in their respective sensitivity to procaine. To examine whether the emptying of the InsP3-sensitive Ca2+ store is the signal for activating the agonist-evoked Ca2+ entry, we have investigated the effects of thapsigargin (TSG), a known inhibitor of the microsomal Ca(2+)-ATPase activity in a variety of cell types, via the activity of calcium-activated potassium channels [K(Ca2+) channels]. In cell-attached experiments, the external application of TSG caused a sustained or oscillatory activation of K(Ca2+) channels depending on both the cells and doses tested. The TSG-evoked channel activity could be reversibly blocked by removing extracellular Ca2+, and strongly decreased by adding 10 mM procaine to the bath medium. In Ca(2+)-free external conditions, TSG did not promote an apparent Ca2+ discharge from internal stores but prevented in a dose- and time-dependent manner the subsequent agonist-evoked channel activity related to the release of internally sequestered Ca2+. These results confirm that TSG and BK release Ca2+ from the same internal stores but with different kinetics. Because the channel response to caffeine was found to be poorly sensitive to procaine, in contrast to that evoked by BK and TSG, it may be concluded that both BK and TSG activate the same Ca2+ entry pathway. Therefore, the emptying of the InsP3-sensitive Ca2+ store is likely to be the main signal for activating the agonist-evoked Ca2+ entry in BAE cells. PMID- 1291683 TI - A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve. AB - A novel potassium-selective channel which is active at membrane potentials between -100 mV and +40 mV has been identified in peripheral myelinated axons of Xenopus laevis using the patch-clamp technique. At negative potentials with 105 mM-K on both sides of the membrane, the channel at 1 kHz resolution showed a series of brief openings and closings interrupted by longer closings, resulting in a flickery bursting activity. Measurements with resolution up to 10 kHz revealed a single-channel conductance of 49 pS with 105 mM-K and 17 pS with 2.5 mM-K on the outer side of the membrane. The channel was selective for K ions over Na ions (PNa/PK = 0.033). The probability of being within a burst in outside-out patches varied from patch to patch (> 0.2, but often > 0.9), and was independent of membrane potential. Open-time histograms were satisfactorily described with a single exponential (tau o = 0.09 msec), closed times with the sum of three exponentials (tau c = 0.13, 5.9, and 36.6 msec). Sensitivity to external tetraethylammonium was comparatively low (IC50 = 19.0 mM). External Cs ions reduced the apparent unitary conductance for inward currents at Em = -90 mV (IC50 = 1.1 mM). Ba and, more potently, Zn ions lowered not only the apparent single channel conductance but also open probability. The local anesthetic bupivacaine with high potency reduced probability of being within a burst (IC50 = 165 nM). The flickering K channel is clearly different from the other five types of K channels identified so far in the same preparation. We suggest that this channel may form the molecular basis of the resting potential in vertebrate myelinated axons. PMID- 1291685 TI - Human responses to the diagnosis of choroidal melanoma. AB - Patient responses to the diagnosis of choroidal melanoma are individual and sometimes unexpected. Nurses are in a perfect position to ascertain a cancer patient's feelings, to listen, and to provide emotional support. Patient reactions to the diagnosis of choroidal melanoma can range from fear of blindness to concern for their children. PMID- 1291686 TI - The excimer laser: program implementation and nursing implications. AB - The excimer laser is a low energy level laser used in the correction of myopia and removal of corneal scars. The technique, known as photoablation, produces a new kind of laser-tissue exchange where the corneal tissue is transferred into a gaseous state that is expelled from the surface. Predetermined layers of corneal tissue are removed without injury to surrounding tissue. Reshaping the cornea's central optic zone is visually equivalent to placing a contact lens on the eye. PMID- 1291687 TI - Inflammatory orbital pseudotumor. AB - 1. Inflammatory orbital pseudotumor, a term used to describe any idiopathic inflammatory lesion of orbital tissue that simulates a neoplasm of the orbit, is a definite clinical entity masquerading in various forms and covering a wide spectrum of periocular lesions. 2. Inflammatory orbital pseudotumor has a good prognosis with steroid therapy. Once it is suspected, prompt and effective treatment must be given as soon as possible, even before laboratory work-up has been completed. 3. A great deal of investigative study must be done to rule out any other life-threatening diseases. Long-term follow-up is mandatory because malignant or monoclonal transformation is possible. PMID- 1291688 TI - Lisa Rovick, CO, COMT, BA. Interview by Norma Garber. PMID- 1291689 TI - Squamous cell carcinoma of the conjunctiva. PMID- 1291690 TI - Learning the language of contact lenses. PMID- 1291691 TI - Biomechanical aspects of a fluid percussion model of brain injury. AB - The fluid percussion model is in widespread use for the study of brain injury. However, the tissue deformation characteristics of the model have not been determined. Studies have suggested that at high levels of fluid percussion, the fluid percussion model is primarily a model of brainstem injury. It was proposed that this occurs as a direct result of the volume influx to the cranial vault at the moment of impact. This study examines the biomechanical deformation produced by the fluid percussion model. The purpose of this investigation was to describe the regional strain distribution in brain tissue at the moment of impact and to determine the effect of volume efflux produced by the percussion device. A cat skull was sectioned parasagittally and filled with an optically transparent gel. A grid pattern was painted in the midsagittal plane and was used to record the surrogate brain tissue deformation in response to fluid percussion loading. Motion of the grid pattern at low and high levels of fluid percussion loading was recorded using a high-speed camera, and a series of photographs developed from the high-speed film were analyzed to determine the intracranial strain distribution at these loading levels. The results of these studies indicated that the maximum site of strain was located in the region of the lower brainstem and that deformations were negligible in other regions of the brain. These studies provide an explanation for the pathophysiologic results obtained in a parallel series of experiments from which it was concluded that high-level fluid percussion is predominantly a model of lower brainstem injury. PMID- 1291692 TI - Expression of c-fos in the hippocampus following mild and moderate fluid percussion brain injury. AB - An oncoprotein mediator of gene expression, c-fos, was evaluated in the central fluid percussion model of traumatic brain injury (TBI). Since hippocampal CA1 neurons are particularly vulnerable to TBI, we hypothesized that TBI may produce pathobiologic changes in CA1, in part, by alterations in gene expression through c-fos. Sprague-Dawley rats were subjected to mild (1.0 atm) or moderate (2.1 atm) fluid percussion TBI or sham injury. At 15 min, 1 h, and 24 h after injury (or sham injury), sections from middorsal hippocampus were immunostained with antibodies to c-fos, and c-fos-positive CA1 neurons were counted. As predicted, c fos was localized in the nuclei of CA1 pyramidal neurons. However, the intensity of label was not equal over all CA1 neurons. Cells with high-intensity c-fos label were more prevalent after mild TBI. The number of c-fos-labeled CA1 neurons was increased at 15 min after both mild and moderate TBI relative to paired sham controls. Counts of c-fos-positive neurons remained significantly elevated at 1 h postinjury only after mild TBI. By 24 h postinjury, the number of c-fos-positive cells at both injury levels was not different from sham controls. No difference was observed between the number of c-fos-positive cells in naive and sham controls. However, label intensity was slightly less in the naive cases. These results suggest that the pathobiologic changes at early intervals following mild or moderate TBI may involve c-fos alteration of gene expression and that c-fos expression may be differentially regulated as a function of injury level. PMID- 1291693 TI - Breakdown of the blood-brain barrier after fluid percussion brain injury in the rat: Part 2: Effect of hypoxia on permeability to plasma proteins. AB - Clinical studies have demonstrated that hypoxia after severe brain injury is common and significantly worsens neurologic outcome. We have, therefore, developed a rat model of posttraumatic hypoxic injury in order to identify the pathophysiologic responses after head injury that are worsened by this secondary insult. We examined the effect of hypoxia after brain injury on permeability of the blood-brain barrier to plasma proteins. Animals were divided into two experimental groups: group I (impact alone) and group IH (impact plus hypoxia). Rats were subjected to a lateral fluid percussive brain injury (4.8-5.2 atm). Animals in group IH were exposed to hypoxic conditions (10% O2) for 45 min immediately after injury. In each group, vascular permeability to endogenous immunoglobulins (IgG) and to horseradish peroxidase (HRP) was examined at the light microscopic level. IgG was immunolocalized in brain sections at 1-24 h after injury. In other studies, HRP was given i.v. either before impact or 10 min before killing. Permeability to this protein was assessed at 1-72 h after injury. The distribution of extravasated proteins was similar between the experimental groups at 1 h postinjury. Pronounced abnormal permeability to IgG and HRP (given before impact) occurred in discrete regions throughout both the ipsilateral and contralateral hemispheres. By 6 h after injury, a differential response of the blood-brain barrier was noted between groups I and IH. Widespread leakage of proteins was observed in the injured hemisphere in group IH. This finding was in sharp contrast to group I, in which extravasated proteins remained more localized in the injured hemisphere. The time course for reestablishment of the blood-brain barrier to HRP (given before killing) was determined. The impact site remained permeable to HRP up to at least 72 h postinjury within groups I and IH. In group I, the blood-brain barrier was reestablished in the parasagittal cortex and deep cortical layer by 6 h postinjury. In contrast, the blood-brain barrier in group IH was not restored in similar brain regions until 24 h postinjury. These studies demonstrate that (1) hypoxia after brain injury exacerbates the regional breakdown of the blood-brain barrier to circulating proteins, (2) this influence of hypoxia on permeability is not apparent immediately after injury but rather is expressed at 6 h after injury, and (3) hypoxia after traumatic brain injury delays recovery of the blood-brain barrier. These findings suggest that secondary posttraumatic hypoxia contributes to the vascular pathogenesis of brain injury. PMID- 1291694 TI - Endothelium-dependent responses after experimental brain injury. AB - We examined the effect of fluid percussion brain injury on the responses to topical application of acetylcholine and serotonin, two vasoactive agents that have endothelium-dependent effects, in anesthetized cats equipped with cranial windows. Before brain injury, topical acetylcholine dilated both small and large arterioles. Thirty minutes after brain injury, acetylcholine constricted small arterioles, and the vasodilator response of large vessels was abolished. Subsequent application either of superoxide dismutase plus catalase to eliminate superoxide and hydrogen peroxide or of deferoxamine, an agent that scavenges iron and inhibits the production of hydroxyl radical via the Haber-Weiss reaction, restored the normal vasodilator responses to acetylcholine. Serotonin constricted both large and small arterioles before brain injury. After brain injury, small arterioles responded with a small vasodilation, and the response of large arterioles was abolished. After application of superoxide dismutase and catalase, the normal vasoconstrictor response to serotonin was restored. The results show that endothelium-dependent vasodilation from acetylcholine is eliminated by brain injury by a mechanism that involves the generation of oxygen radicals, and, more specifically, the production of hydroxyl radical. The results with serotonin are explained by the elimination by oxygen radicals of a vasoconstrictor agent generated by this agent, perhaps an endothelium-derived contracting factor. PMID- 1291695 TI - Continuous monitoring of posttraumatic cerebral blood flow using laser-Doppler flowmetry. AB - Traumatic brain injury causes alterations in cerebral blood flow that are thought to influence secondary pathophysiology and neurologic outcome in humans. Since it is difficult to study early changes in blood flow in head-injured patients, animal models of brain injury must be employed. However, techniques to monitor brain blood flow in animals are labor intensive and generally provide discontinuous flow measurements. The present study examines the application of laser-Doppler flowmetry for measurement of cerebral blood flow following experimental brain injury. This method allows continuous monitoring of local cerebral blood flow before, during, and after injury. Rats (n = 9) were prepared for lateral fluid percussion injury under barbiturate anesthesia. Injury (2.10 +/ 0.02 atm) was induced over the right parietal cortex, and blood flow was monitored in the contralateral cortex. Seconds after the peak hypertension after injury, blood flow in the left parietal cortex increased 226% +/- 18% (means +/- SEM). This increase was transient, with blood flow falling below control values within minutes. Five minutes after injury, blood flow was 83% +/- 8% of control, and at 1 h, this value had fallen to 56% +/- 6%. Blood flow at 60 min was 93% +/- 5% of control in the sham-injured group (n = 10). The reduction in cerebral blood flow in our laser-Doppler study was of similar magnitude as previously reported in rats injured at a similar intensity when blood flow was examined with radiolabeled microspheres. Given these results, we believe laser-Doppler flowmetry can be used to continuously monitor posttraumatic blood flow following experimental brain injury. PMID- 1291696 TI - Motor power differences within the first two weeks post-SCI in cervical spinal cord-injured quadriplegic subjects. AB - The purpose of this study was to confirm the clinical impression that motor power significantly changed within the first 2 weeks after a spinal cord injury (SCI) and to determine the time for motor power assessment within the first 2 weeks post injury that best correlated with motor power determined 6 months post-SCI. Our hypothesis was that within the first 2 weeks postinjury, the manual muscle test (MMT) scores would change significantly from the < or = 24 h examination and that the post-24 h evaluations of strength would have a higher correlation with the 6 month measure of motor outcome than the evaluation of strength performed < or = 24 h after SCI. The biceps, extensor carpi radialis, triceps, flexor digitorum profundus, and interosseous muscle strength was measured in 40 subjects using the MMT (muscles graded 0/5 to 5/5) at < or = 24 h, 72 h, 1 week, 2 weeks, 3 months, and 6 months post-SCI. Upper extremity motor index scores (MIS) obtained at the four testing periods within 2 weeks of injury were analyzed using a Friedman analysis of variance with Duncan's post-hoc tests to identify significant differences. Separate analyses were performed on subgroupings of the total sample based on the strength of the most rostral key muscle having less than antigravity strength. There were three groups evaluated: initial MMT 0/5 (n = 22), initial MMT 1-1.5/5 (n = 17), and initial MMT 2-2.5/5 (n = 13).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291697 TI - An empirical evaluation of behavioral and cognitive-behavioral group marital treatments with discordant couples. AB - Previous research has revealed that group behavioral therapy for distressed couples provides an effective and efficient form of marital treatment. However, research comparing alternative group approaches is lacking. The current investigation evaluated group behavioral and cognitive-behavioral marital treatments across a variety of relationship dimensions and measures of individual functioning. Dysfunctional couples were randomly assigned to experimental conditions and demonstrated statistically and clinically significant improvement as contrasted with the waiting list control group. These results are discussed in terms of the differences between treatment conditions, potential advances in the field of marital therapy, and recommendations for further inquiry. PMID- 1291698 TI - Stress, sexual satisfaction, and marital adjustment in infertile couples. AB - A longitudinal study was designed to assess the effects of infertility as well as the influence of the subsequent medical investigation on marital functioning. During their initial visit at a fertility clinic, 165 couples underwent psychological assessment. Questionnaires were completed to assess stress, sexual satisfaction, and marital adjustment. Participants were categorized into those who became pregnant during the 12 months of the study (n = 48 couples) and those for whom treatment was not successful (n = 117 couples). Significant increases in stress and decreases in marital functioning were experienced by subjects as the treatment investigation progressed. Furthermore, greater levels of marital distress were observed in couples that did not conceive. Significant gender differences were observed. PMID- 1291699 TI - Does the CAT technique enhance female orgasm? AB - The following is a report of The Human Sexuality Program of the New York Hospital Cornell Medical Center to personally replicate Edward W. Eichel's claims that his Coital Alignment Technique (CAT) enhances and increases female coital orgasms and mutual orgasms. We failed to replicate these claims. However, it was the consensus of the group that within the context of sex therapy, the CAT technique may have merit in certain clinical situations, and as such deserves to be further evaluated. PMID- 1291701 TI - Sexual addiction: designation and treatment. AB - While there is general agreement that the pattern of behavior described as "sexual compulsivity" or "sexual dependency" or "sexual addiction" does exist, considerable controversy surrounds the issue of how this syndrome should be designated. The principle candidates--compulsivity, dependency, and addiction- are examined, and addiction is found to be the most suitable term. Addiction is then clearly defined, and diagnostic criteria for addictive disorder are specified. After the definition of and diagnostic criteria for sexual addiction are presented, arguments against the concept of sexual addiction are reviewed and answered. Implications of this concept for treatment are then explored. PMID- 1291700 TI - The long-term use of cyproterone acetate in pedophilia: a case study. AB - This investigation reports the long-term use of the antiandrogen cyproterone acetate (CPA) in a pedophile, who was studied continuously over 38 months. Measures of sexual arousal, serum testosterone, and gonadotropin levels were significantly reduced by the drug as compared with placebo and no treatment; prolactin levels were significantly elevated. Some workers have observed that long-term administration of CPA (more than one year, which was then discontinued) produced enduring (in some cases apparently permanent) anti-libidinal effects; however, in the case described, within three weeks of stopping the drug, all measures had returned to pretrial levels. The importance of continuous long-term monitoring in sex offenders receiving an antiandrogen is discussed. PMID- 1291702 TI - The female sensation seeker and marital sexuality. AB - To examine the role of sensation seeking in female sexuality, the Zuckerman's Sensation Seeking Scale was administered to a nonclinical population of married women. Comparative assessments were made between two matched samples of high and low sensation seekers on frequency of sexual intercourse, marital satisfaction, sexual desire, sexual arousal, sexual assertiveness, sexual attitudes, and sexual satisfaction. Although the high sensation seekers demonstrated significantly greater sexual desire, sexual arousability, and a more positive attitude toward sex, there were surprisingly no differences between the groups on frequency of sexual intercourse and sexual assertiveness. Also, the women classed as low sensation seekers reported greater marital and sexual satisfaction. PMID- 1291703 TI - Bisoprolol and hypertension: effects on sexual functioning in men. AB - OBJECTIVES: To investigate prospectively the effects of the selective beta 1 adrenoceptor blocker bisoprolol on sexuality of men with hypertension. DESIGN: In newly diagnosed patients (group I): double-blind, crossover, placebo controlled. In men with hypertension on antihypertensive treatment (group II): crossover design. SETTING: Large area in and around Rotterdam, The Netherlands. PATIENTS: Twenty-six men (criteria: between 25 and 70; no disease etc. known to affect sexual functioning) were recruited through their general practitioners. Group I (n = 13) fulfilled the selection criteria, sitting blood pressure systolic > or = 160 mm Hg and/or diastolic > or = 95 mm Hg, measured on 3 different days. Group II (n = 13) patients already on antihypertensive treatment. MAIN OUTCOME MEASURES: Data on blood pressure. Qualitative and quantitative data on sexuality through questionnaires, including personal and sexual history, sexual functioning, sexual satisfaction and erectile difficulties. RESULTS: Bisoprolol is an effective antihypertensive drug with no detrimental effects on sexuality in newly diagnosed men with hypertension. In men already on antihypertensive medication bisoprolol improved sexuality in some parameters, i.e. firmness of erection during coitus, contentedness with sexual functioning and satisfaction with own sexuality. CONCLUSION: Bisoprolol is an effective antihypertensive agent with no sexual side effects. PMID- 1291704 TI - [Abnormal intracellular calcium handling as a cause of diastolic dysfunction in the failing myocardium]. PMID- 1291705 TI - [Disruption of microtubule structure in the failing myocardium]. PMID- 1291706 TI - [Molecular mechanism of diastolic dysfunction in pressure overload cardiac hypertrophy]. PMID- 1291707 TI - [Mechanism responsible for age-related deterioration of cardiac performance- aging of mitochondrial DNA]. PMID- 1291708 TI - [In vitro studies on the kinetic property of cardiac contractile proteins]. PMID- 1291709 TI - [Free radical production has an important role in disturbance in myocardial functions in cardiomyopathy hamsters--vitamin E improves myocardial damage and survival]. PMID- 1291710 TI - [Effects of oxygen free radicals on Ca2+ binding to cardiac troponin]. PMID- 1291711 TI - [Radionuclide assessment of myocardial failure: importance of metabolic mapping]. PMID- 1291712 TI - [Autocrine and paracrine effects of EDRF--analysis of intracellular Ca2+ handling processes in endothelial cells and vascular smooth muscle cells in coculture]. PMID- 1291713 TI - [Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells]. PMID- 1291714 TI - [Possible mechanisms of inhibitory effects of atherosclerosis and lipoproteins on EDRF]. PMID- 1291715 TI - [Endothelin-1 as an autocrine factor in hypertrophy of cardiomyocytes]. PMID- 1291716 TI - [Blood pressure regulation and endothelin]. PMID- 1291717 TI - [The role of ATP sensitive potassium channel on the electrical derangement during hypoxia and reperfusion]. PMID- 1291718 TI - [Activation of cardiac ATP-sensitive potassium channels by internal acidosis]. PMID- 1291719 TI - [On the regulation of cardiac K channel by GTP-binding proteins--basic mechanism and clinical aspect of acetylcholine and adenosine-increase of cardiac potassium conductance]. PMID- 1291720 TI - [Changes in the treatment procedures for mitral stenosis]. PMID- 1291721 TI - [Percutaneous transvenous mitral commissurotomy with the Inoue balloon catheter in adults--immediate results and long-term follow-up]. PMID- 1291722 TI - [Technical improvement in PTMC (percutaneous transvenous mitral commissurotomy)]. PMID- 1291723 TI - [Effect on hemodynamic parameters and exercise tolerance by PTMC]. PMID- 1291724 TI - [Comparison of long-term outcome of closed mitral commissurotomy versus open mitral commissurotomy and mitral valve replacement]. PMID- 1291725 TI - [Role and limitation of percutaneous transluminal mitral commissurotomy]. PMID- 1291726 TI - [Left ventricular function in mitral regurgitation--relation to postoperative survival and left ventricular contractile state after mitral valve replacement]. PMID- 1291727 TI - [The effect of mitral valve replacement with preservation of mitral complex on left ventricular function in mitral regurgitation]. PMID- 1291728 TI - [Reconstruction for mitral regurgitation--its long-term results and the extension of its application]. PMID- 1291729 TI - [Analysis of left ventricular performance after mitral valve replacement with a technique of preservation of all chordae tendineae: comparison with conventional mitral valve replacement or mitral valve repair]. PMID- 1291730 TI - [Thrombolytic therapy of acute myocardial infarction--effects, problems and their strategies]. PMID- 1291731 TI - [Short and long-term effects of coronary thrombolysis in acute myocardial infarction]. PMID- 1291732 TI - [Efficacy of direct PTCA for acute myocardial infarction complicated by cardiogenic shock]. PMID- 1291733 TI - [Thrombolysis and coronary angioplasty for acute myocardial infarction: usefulness of combination therapy]. PMID- 1291734 TI - [Early occlusion of the infarct-related artery after emergency PTCA for acute myocardial infarction]. PMID- 1291735 TI - [Implication and controversy of rescue coronary angioplasty in patients with acute myocardial infarction]. PMID- 1291736 TI - [The choice of therapy for recanalization in patients with acute myocardial infarction and the prevention of the acute reocclusion after recanalization]. PMID- 1291737 TI - [Prevention of left ventricular dilation without infarct size limitation by late reperfusion in patients with acute myocardial infarction]. PMID- 1291738 TI - [Acquisition of myocardial ischemic tolerance and its clinical significance]. PMID- 1291739 TI - [Surgical treatment using percutaneous cardiopulmonary bypass in cardiac arrest patients with acute myocardial infarction]. PMID- 1291740 TI - [Electrophysiologic testing and effects of antiarrhythmic drugs in patients with paroxysmal supraventricular tachycardia]. PMID- 1291741 TI - [Evaluation of drug efficacy for preventing paroxysmal atrial fibrillation]. PMID- 1291742 TI - [Clinical significance of electrophysiologic drug testing in the longterm therapy of class I, III and IV antiarrhythmic drugs for recurrent ventricular tachyarrhythmia]. PMID- 1291743 TI - [Characteristics of drug-refractory sustained ventricular tachycardia]. PMID- 1291744 TI - [Evaluation of efficacy of amiodarone by electrophysiologic studies in patients with sustained ventricular tachycardia]. PMID- 1291745 TI - [Actions of antiarrhythmic drug on the reentrant circuit of sustained ventricular tachycardia]. PMID- 1291746 TI - [Pharmacokinetics and pharmacodynamics of class I antiarrhythmic agents after a single oral administration]. PMID- 1291747 TI - [Silent myocardial ischemia: its concept and basic aspect]. PMID- 1291748 TI - [Detection and treatment of silent myocardial ischemia]. PMID- 1291749 TI - [Clinical characteristics and the prognosis in patients with silent ischemia: presentation of cases]. PMID- 1291750 TI - [The importance of coronary angiography in understanding of ischemic heart disease]. PMID- 1291751 TI - [Long-term prognosis after coronary artery bypass surgery and some factors related to vein graft stenosis]. PMID- 1291752 TI - [Indication of coronary angiography for asymptomatic ischemic heart disease]. PMID- 1291754 TI - [Survey of diagnostic criteria for arrhythmia--1992 report]. PMID- 1291753 TI - [Standard levels of respiratory circulation parameters during exercise--1990 report]. PMID- 1291755 TI - Evaluation of an improved dot-immunobinding assay for carcinoembryonic antigen determination in nipple discharge in early breast cancer: results of a multicenter study. AB - We have previously reported carcinoembryonic antigen (CEA) measurement in nipple discharge to be a useful adjunct in the diagnosis of non-palpable breast cancer. We have now developed a "microdot-immunobinding assay" using a specially constructed device to screen efficiently large numbers of patients with nipple discharge for non-palpable breast cancer. The method is as follows: a sample of nipple discharge is placed on a solid phase monoclonal anti-CEA antibody and, if CEA is present in the discharge, it will be detected by a second monoclonal anti CEA antibody conjugated with alkaline phosphatase. The use of bromochloroindolyl phosphate as a chromogen results in a stable color reaction that can be semiquantitatively analyzed with the naked eye. CEA levels determined by this microdot assay correlated well with those determined using the earlier Elmotec assay. To determine the accuracy of the method, a collaborative study involving 11 institutes in Japan was organized. The CEA levels in nipple discharges from 77 patients undergoing surgery, 44 of whom were diagnosed as having breast cancer, were assayed. The results were that 17 of the 23 patients with palpable breast cancer, and 16 of the 21 patients with non-palpable breast cancer exhibited CEA values > 400 ng/ml, a cut-off value determined in a previous study. The overall accuracy (78%) of this test for diagnosing non-palpable breast cancer was higher than that obtained from ductography or cytology. The system may thus be of use in the screening of early breast cancer. PMID- 1291756 TI - Microcarcinoma of the endometrium: a mapping study with special reference to cytologic atypia in the endometrium. AB - In order to elucidate the basis for the development of an endometrial carcinoma, we looked for microcarcinomas measuring < 5 mm in greatest diameter, and studied their histologic characteristics and those of the neighboring endometrium. Using serial step section methods, two microcarcinomas were detected. A microcarcinoma was found in one of 14 uteri resected for atypical hyperplasia and the other was found in one of 114 uteri resected for endometrial carcinoma. The neighboring endometrium of the former was adenomatous and had atypical hyperplasia and that of the latter was atrophic and contained atypical glands characterized by cytologic atypia and not by architectural changes. The findings may suggest endometrial carcinomas to have two pathogenetic forms: a carcinoma associated with hyperplasia and occurring in premenopausal women, a second carcinoma associated with atrophic endometrium and occurring in postmenopausal women. Atypical glands in atrophic endometria may indicate that endometrial specimens from postmenopausal women should be carefully screened for cytologic atypia. PMID- 1291757 TI - Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group. AB - Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2' deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL. PMID- 1291758 TI - Cardiac tamponade in chronic myelomonocytic leukemia: a case report. AB - Serous effusion is a rare complication of chronic myelomonocytic leukemia. We present a patient with chronic myelomonocytic leukemia who developed a massive pericardial effusion with cardiac tamponade as early manifestations. Numerous clumps of monocytes were observed in the effusion. The patient obtained rapid relief following the intravenous administration of etoposide (100 mg daily for 5 days). Few reports have documented details of such a case. PMID- 1291759 TI - A case of hypersensitivity syndrome resembling Langerhans cell histiocytosis during phenobarbital prophylaxis for convulsion. AB - The case of a two-year-old girl with generalized histiocytosis, probably induced by phenobarbital, is reported. Symptoms, including intermittent fever, systemic lymphadenopathy, maculopapular skin eruption and hepatosplenomegaly, suggested Langerhans cell histiocytosis. Laboratory examinations revealed leukocytosis with lymphocytosis and eosinophilia and a high LDH serum level, while GOT and GPT were within normal ranges. Cytological studies of lymph node and pleural effusion specimens revealed proliferation and infiltration of Langerhans cell histiocytes with eosinophilia. No histiocyte proliferation was observed in the bone marrow or skin. The clinical manifestations shown by the patient were, however, transient, and improved spontaneously after the discontinuation of phenobarbital. The case was considered to be one of phenobarbital hypersensitivity syndrome based on clinical course and laboratory findings. The mechanism and differential diagnosis of the syndrome are discussed. PMID- 1291761 TI - Cancer mortality trends in Japan 1960-1990: three-dimensional graphical presentation. PMID- 1291760 TI - Changing patterns of cancer mortality among the elderly population in Japan. PMID- 1291762 TI - Cancer incidence and incidence rates in Japan in 1987: estimates based on data from nine population-based cancer registries. The Research Group for Population based Cancer Registration in Japan. PMID- 1291763 TI - A vertically transmitted HIV-1 gag-subtype variant detected in Taiwan. AB - We used polymerase chain reaction (PCR) to amplify a segment, about 560 base pairs (bp), of HIV-1 gag DNA prepared from peripheral blood mononuclear cells of a seropositive Taiwanese pair of mother and infant. TM-1 and TC-1 clones of PCR amplified DNA derived from the mother and infant, respectively, showed a 94.5% homology with each other. However, the TM-1 and TC-1 sequences exhibited lower degrees of homology, i.e. only 85.1% and 85.8%, respectively, with the corresponding gag segment of a North American HIV-1 subtype (HXB2), and 86.4% and 87.0%, respectively, with that of a Zairean HIV-1 subtype (Z2Z6). The divergence of TM-1 and TC-1 sequences from those of HXB2 and Z2Z6 is particularly prominent in the first (5' proximal) 200 bp of the cloned DNA segment, involving transitions more frequently than transversions. Two additional clones TM-2 and TC 2 derived from the mother and infant were sequenced for the first 200 bp. These four clones showed a high degree of homology (94.7-97.5%) among themselves, providing an evidence for transmission of the virus from the mother to the infant. These findings show the epidemiological value of PCR, and indicate the presence of a gag subtype of HIV-1 which is distinct from both the North American and Zairean subtypes according to the phylogenetic tree constructed. PMID- 1291765 TI - Retraction notice. Evaluation of ELISA for detection of Giardia lamblia-specific copro-antigen employing monospecific antibodies. PMID- 1291764 TI - Mitochondrial malate dehydrogenase and malic enzyme of a filarial worm Setaria digitata: some properties and effects of drugs and herbal extracts. AB - Mitochondrial malate dehydrogenase (mMDH) and malic enzyme (mME) of a filarial worm Setaria digitata were studied. mMDH exhibited the highest activities in the oxidation and reduction reactions at pH 9.5 and pH 6.2, respectively, while mME did so in the malate decarboxylation reaction at pH 6.8. mME showed no detectable activity on the pyruvate carboxylation direction. The Km values for malate (1.7 mM) and oxaloacetate (0.17 mM) and the ratio of Vmax oxidation: Vmax reduction (2.73) tend to favor the oxaloacetate reduction by mMDH. mME showed a relatively high Km value of 8.3 mM, for malate decarboxylation. A drug, diethylcarbamazine citrate (DEC-C), did not change appreciably the activity of either mMDH or mME, while filarin (a drug of herbal origin) effectively inhibited mMDH. The leaf extracts of Ocimum sanctum, Lawsonia inermis and Calotropis gigantea and leaf and flower extracts of Azadirachta indica were, however, found to inhibit both mMDH and mME. PMID- 1291766 TI - [The 22nd Regional Meeting of East and West of Japan, Japanese Society of Nephrology. May 23-29, 1992. Abstracts]. PMID- 1291767 TI - [The use of the contact periodic-pulse laser and microwave scalpels in liver surgery]. AB - In use of the laser (CPPLS) and microwave (MWS) scalpels, the reliability of arrest of bleeding and bile leakage has been proved not only at studies on the intact liver but on the models of jaundice with impaired coagulative blood properties as well. After hepatic resection by means of CPPLS and MWS, the impairement in its functional state lasts for a short time. In use of CPPLS, disturbance in tissue blood flow is less than in use of MWS. Healing of the wounds inflicted by CPPLS and MWS occurs in absence of pronounced exudative and inflammatory reactions. In a wound inflicted by a laser scalpel, the necrotic layer is not pronounced. It is expedient to use the CPPLS and MWS in patients with hepatic masses in technically difficult cholecystectomy as they contribute to decrease in intraoperative blood loss and prevention of the development of complications after the operation. PMID- 1291768 TI - [The use of the zonal electrophoresis of antibiotics in acute destructive cholecystitis complicated by suppurative cholangitis]. AB - At experimental investigations on 38 adult dogs for studying pharmacokinetics of kanamycin in the bile and liver tissue under the influence of the electric field of constant current, the increase in concentration of the preparation as compared with that in the control group was established. Optimal concentration of kanamycin retained for 14-16 h. Clinical study has shown the high effectiveness of the method for treatment of acute cholangitis suggested. PMID- 1291769 TI - [The use of the neodymium-YAG laser in thoracic surgery]. AB - The technique of use of a neodymium YAG-laser for surgical treatment of diseases of the lungs and pleura in 25 patients is described. The experience accumulated is indicative of good aero- and hemostatic properties of the laser, which permit to reduce the incidence of postoperative complications. PMID- 1291770 TI - [The characteristics of the adaptive-recovery reactions of children after lung resection in chronic respiratory organ diseases]. AB - The results of examination of 80 children at the late postoperative period are indicative of gradual progression of the reparative-restorative processes 1 year after the operation already. Diffuse purulent endobronchitis preserves for one year, purulent endobronchitis on the non-operated side-up to 3 years, at a zone of the operative intervention, local inflammatory process is defined more than 3 years later. In half of the children operated on, exacerbations of the bronchial tree disease with formation in some of them of the combined changes in hemodynamics and external respiration were revealed. PMID- 1291771 TI - [The clinical picture and diagnosis of the pharyngofacial form of myasthenia]. AB - In the clinic, 564 patients with the different forms of myasthenia were operated on. A pharyngo-facial form of myasthenia was revealed in 65 (11.5%) of them. There are the following clinical peculiarities of a pharyngo-facial form of myasthenia: involvement of the pharyngeal and facial muscles, impaired phonation, jerky speech, sensation of the tongue heaviness. The direction of process generalization is commonly from the centre towards periphery, towards the skeletal muscles. Involvement of the muscles of the soft palate, epiglottis causes saliva and pharyngeal secret flowing into the bronchi which leads to asphyxia. PMID- 1291773 TI - [The effect of dalargin on the course of mechanical trauma]. PMID- 1291772 TI - [The correction of functional disorders of the hemostatic system and of the rheological properties of the blood in dogs in the late period of hemorrhagic shock by the intravenous transfusion of lactoprotein]. AB - In 9 dogs with severe hemorrhagic shock, the effect of hemocorrector "Lactoprotein" on the indices of coagulative hemostasis and rheologic blood properties was studied. It was established that in intravenous transfusion of lactoprotein at a dose of 10 ml/kg permitting to lead the animals out from the state of shock, the syndromes of disseminated intravascular coagulation and high viscosity of the blood were cupped off. However, by the end of 48 hours of observation, fibrinogen level in the blood of the animals increased sharply, while antithrombin-III concentration and hematocrit decreased. Together with recommendation to use lactoprotein in the complex of shock therapy at all the stages of medical evacuation, the conclusion about necessity to perform at the early postshock period the differential component hemo- and anticoagulative therapy has been made. PMID- 1291774 TI - [The use of biosporin in treating an experimental suppurative wound]. AB - The effect of biosporin biopreparation on the agents of suppurative wound infection in the experiment on rabbits was studied. A positive effect of the preparation on healing of a suppurative wound was noted. PMID- 1291775 TI - [Lymphosorption in the combined treatment of jaundice]. AB - Drainage of the thoracic lymph duct and lymphosorption were used in 63 patients with obstructive jaundice of different etiology and cholestatic hepatitis. Lymph was returned into the umbilical vein with transfusion of proteins, glucose, steroid hormones and other preparations. PMID- 1291776 TI - [The surgical procedure and treatment of paravesical abscesses in acute cholecystitis in middle-aged and elderly patients]. AB - The results of 238 operations performed for acute cholecystitis within 1985-1990 have been analysed. Of them in 11 (4.6%), paravesical (8 cases) and intrahepatic (3) abscesses were revealed. In 8 patients, the presence of an abscess at the preoperative period was supposed. All the patients were admitted to the hospital later than 24 h from the onset of the disease and operated on within 1 to 5 days. Perforation of the gallbladder was revealed in 5 patients, gangrene with destruction of its wall--in 3. Abscess location near the gallbladder fundus was noted in 4 patients, near its neck--in 2, along the medial surface--in 2. A unicameral abscess was revealed in 5 cases, a multicameral one--in 3. The operative treatment presents technical difficulties and consists in performance of cholecystectomy (sometimes--Pribram's mucoclasis), external drainage of the common bile duct and abscess cavity, drainage of the subhepatic and subphrenic space. One 82-year old patient died. PMID- 1291777 TI - [The use of cholesorption in the treatment of patients with acute cholecystitis complicated by cholangitis]. AB - The results of treatment of 137 patients with acute cholecystitis complicated by cholangitis are presented. The causes and clinical signs, and tactics for operative treatment of the disease are described. Progressive hepatic failure is one of the causes of lethality. Use of the developed method of cholesorption permitted to reduce the incidence of hepatic failure development, decrease postoperative lethality to 9.5%. PMID- 1291778 TI - [The diagnostic characteristics and surgical treatment of acute cholecystitis in middle-aged and elderly patients]. AB - From 1980 to 1990, 340 elderly and senile patients underwent treatment for acute cholecystitis. Of them, 109 were operated on. To diagnose the disease, immunologic reactivity of an organism was considered. Diagnostic errors were made in 10.2% of cases. Three patients died. PMID- 1291779 TI - [The dissolution via the drain of "forgotten" calculi in the common bile duct after surgery]. AB - The results of dissolution of the "lost" concrements in the common bile duct in 12 patients, who underwent urgent operations for acute complicated cholecystitis, with the use of transdrain administration of miscleron, chloroform, novocaine are analysed. A positive result was obtained in 10 patients. PMID- 1291780 TI - [The optimal drainage of the bile ducts and subhepatic recess in the surgical treatment of complicated cholecystitis]. AB - On the basis of the analysis of the results of surgical treatment of 478 patients with complicated cholecystitis, it was established that the Robson-Vishnevsky method (95 cases) was the optimal one for drainage of the bile ducts after diagnostic (19) or therapeutic (115) choledochotomy, and that of Halsted-Pikovsky (9)--in manipulations through the cystic duct. Drainage of the subhepatic space by means of a rubber tube drain is effective. The methods for active decompression and transdrain therapeutic measures used in presence of purulent inflammatory process in the bile ducts, or subhepatic space are presented. PMID- 1291781 TI - [Changes in the microflora of the suppurative cavities resulting from the treatment of acute bacterial destruction of the lungs]. AB - The results of complex bacteriologic examination of 62 patients with acute bacterial destruction of the lungs during the process of treatment were analysed. The complex of investigations included the express methods (bacterioscopy, studies in the ultraviolet light, chromatography-mass spectrometry), inoculation under aerobic and anaerobic conditions. A role of anaerobic non-clostridial infection in the development of acute pulmonary destruction, polymicrobial character of microflora are shown. It was established that complex conservative therapy with inclusion of the methods for drainage of the cavities of destruction, prolonged intraarterial infusion, aimed antibacterial therapy permitted to achieve rapid suppression of microflora, its anaerobic component in particular. In chronization of the disease, the gram-negative aerobic flora is playing the leading part in its pathogenesis. PMID- 1291782 TI - [Kasten's syndrome]. AB - The associated hiatal hernia, chronic cholecystitis and duodenal ulcer disease were diagnosed in 12 patients. Combined surgical operations were performed in 9 patients with a good long-term result. PMID- 1291783 TI - [Selective proximal vagotomy and esophagofundoplication by Nissen's method in treating reflux esophagitis of ulcerous etiology]. AB - In this article, the results of the use of selective proximal vagotomy and Nissen fundoplication in the surgery of reflux esophagitis in patients with ulcer disease of the pyloric gastric portion and duodenum are analysed. Characteristics of a state of acid producing function of the stomach at different periods after the operation is given. The causes of development of the post-fundoplication complications, methods for their treatment are presented. PMID- 1291784 TI - [Exploratory laparotomy in stomach cancer]. AB - The results of performance of exploratory laparotomy in 333 patients with gastric cancer have been analysed. The main reason of the use of laparotomy consists in seldom use of the special methods for diagnosis of tumor spreading. Complex use of laparoscopy and radionuclide methods for diagnosis permits to reduce the number of unsubstantiated laparotomies by 45-50% and bring down the frequency of its performance to 12-15% of the total number of operative interventions in gastric cancer. PMID- 1291785 TI - [Aberrant goiter with an intrastitial localization]. PMID- 1291786 TI - [The diagnosis and treatment of nonparasitic cysts of the liver]. PMID- 1291787 TI - [Ultrasonic scanning and duodenoscopy in the diagnosis and treatment of obstructive jaundice]. AB - In 186 patients with obstructive jaundice admitted to the clinic for diagnosis of its cause, the ultrasound scanning with duodenoscopy was employed. This permitted to establish the cause of jaundice in 84.9% of the patients and to choose proper therapeutic tactics at the shortest time after hospitalization. In 80% of the patients, an obstacle for bile outflow was liquidated by means of endoscopy. When it was not possible to established the cause of jaundice by the findings of ultrasound scanning and duodenoscopy, percutaneous transhepatic cholangiography was performed, which has proved to be successful in 5.9% of cases. Use of the given methods for diagnosis permitted to define the optimal therapeutic tactics in patients with obstructive jaundice, to reduce the lethality. PMID- 1291788 TI - [The pathogenetic aspects of the surgical treatment of reflux esophagitis]. PMID- 1291789 TI - [A needle for performing a water load and cholangiography during the intraoperative revision of the extrahepatic bile ducts]. PMID- 1291790 TI - [Use of a hemostatic clamp and a welt-shaped suture in experimental resection of the spleen]. PMID- 1291791 TI - [A pi- and x-shaped suture of the liver]. PMID- 1291792 TI - [An analysis of mortality after operations on the biliary tract]. PMID- 1291793 TI - [Choledochotomy in the surgery of choledocholithiasis]. PMID- 1291794 TI - [A rare complication of cholelithiasis]. PMID- 1291795 TI - [The clinical diagnosis of anaerobic destructive cholecystitis]. PMID- 1291796 TI - [A cyst of the left hepatic duct as the cause of obstructive jaundice]. PMID- 1291798 TI - [The long-term presence of a foreign body in the bronchus]. PMID- 1291797 TI - [The use of endoscopic laser surgery in treating bronchial adenoma]. PMID- 1291799 TI - [One-stage intrapleural colonic esophagoplasty after an abdominal intervention]. PMID- 1291800 TI - [A chemical burn of the stomach combined with acute pancreatitis]. PMID- 1291801 TI - [Complications in the surgical treatment of cancer of the esophagus and cardia]. PMID- 1291802 TI - [The symptom of undulation of the intercostal spaces in diaphragmatic hernia]. PMID- 1291803 TI - [The treatment of wounds of the heart and pericardium at a district hospital]. PMID- 1291804 TI - [Damage to an endocardial electrode with a suicidal intent]. PMID- 1291805 TI - [Destructive appendicitis in a patient after trauma to the chest and the abdominal wall]. PMID- 1291806 TI - [The use of laparoscopy in the differential diagnosis of a complicated aneurysm of the abdominal aorta and acute pancreatitis]. PMID- 1291808 TI - Alcohol and other drug abuse in the dental culture: a profession coming to terms. PMID- 1291807 TI - [Endovascular regional infusion therapy in the combined treatment of liver abscess]. AB - The comparative assessment of the effectiveness of endovascular regional infusion therapy (ERIT) in the complex of treatment of a hepatic abscess in 16 patients was carried out. In 12 patients, it was performed in combination with surgical intervention, in 4--as an independent method of treatment. In patients with a solitary hepatic abscess, it is expedient to include ERIT into the complex of therapeutic measures in combination with abscess puncture under ultrasound guidance. In presence of multiple abscesses of the liver, ERIT is a method of choice. PMID- 1291809 TI - Clinicopathologic correlation quiz: multilocular radiolucencies of the jaws. PMID- 1291810 TI - Deciduous tooth size standards for American blacks. AB - Normative standards for tooth sizes are valuable for assessing a given patient's status, both clinically and for evaluating intrinsic (e.g., genetic, chromosomal aberrations) and acquired conditions. There are, however, very few published standards for American Blacks and none for the deciduous teeth. Mesiodistal and buccolingual crown diameters are reported here for a series of 100 Black children. As with the permanent dentition, the primary teeth of Blacks are appreciably larger than Whites, though the amount differs by tooth type. In general, while all teeth are larger than norms for Whites, the posterior teeth (m1, m2) are preferentially larger. Applications of these standards are discussed. PMID- 1291811 TI - Macroevolution of plasmids: a model for plasmid speciation. AB - A new evolutionary model for diversification in plasmid incompatibility groups (plasmid speciation) is suggested. The model is based on the formation of plasmid cointegrates from two compatible plasmids. The existence of plasmid cointegrates is well known, however, their potential key role in plasmid macroevolution has not yet been recognized. In a hypothesis presented here, one of the rep genes is supposed to be relaxed from selection in plasmid cointegrates and thus becomes free to accumulate mutations. These mutations can lead to a change in incompatibility specificity. Evidence supporting this hypothesis comes from the common occurrence of multi-replicon plasmids in nature as well as from experimental studies on plasmid cointegrate formation. A more speculative extension of this model hypothesizes an evolutionary scenario for origin of the eubacterial single-replicon genome and the eukaryotic multi-replicon genome, as well as the place of plasmids and viruses in this picture. PMID- 1291812 TI - The cellular toxicity of aluminium. AB - Aluminium is a serious environmental toxicant and is inimical to biota. Omnipresent, it is linked with a number of disorders in man including Alzheimer's disease, Parkinson's dementia and osteomalacia. Evidence supporting aluminium as an aetiological agent in such disorders is not conclusive and suffers principally from a lack of consensus with respect to aluminium's toxic mode of action. Obligatory to the elucidation of toxic mechanisms is an understanding of the biological availability of aluminium. This describes the fate of and response to aluminium in any biological system and is thus an important influence of the toxicity of aluminium. A general theme in much aluminium toxicity is an accelerated cell death. Herein mechanisms are described to account for cell death from both acute and chronic aluminium challenges. Aluminium associations with both extracellular surfaces and intracellular ligands are implicated. The cellular response to aluminium is found to be biphasic having both stimulatory and inhibitory components. In either case the disruption of second messenger systems is observed and GTPase cycles are potential target sites. Specific ligands for aluminium at these sites are unknown though are likely to be proteins upon which oxygen-based functional groups are orientated to give exceptionally strong binding with the free aluminium ion. PMID- 1291813 TI - Viral sex, levels of selection, and the origin of life. AB - Several issues in Chao's related paper J. theor. Biol. (1991, 153, 229-246) are revisited. It is argued that mixes of segments from different viral coinfection groups cannot be regarded as sex, unless one is willing to accept that these groups are replicators and individuals. But, because selection in coinfection groups is dynamically analogous to that in trait groups in structured demes, one should also regard these latter groups as replicators. This approach is unacceptable since the groups in question have irregular ploidies, an unfixed number of parents, and no rules analogous to those of meiosis. It is emphasized, however, that the effective presence of neighbour-modulated fitness can ensure dynamical coexistence of covirus segments, even if the equal net reproduction rate within groups is not warranted. It seems that during the origin of coviruses from complete viruses, a higher-level evolutionary unit has become disintegrated, whereas during the origin of life a higher-level unit, the protocell, has emerged from lower-level ones, i.e. unlinked, replicating genes. These two gene-level systems are not homologous, but analogous. Although it is true that the resistance to parasites and the need to avoid a mutational collapse of the genome are likely to have called for some compartmentation in precellular stages of evolution, no clear demonstration, that the proposed mechanisms (the compartmentalized hypercycle and the stochastic corrector model) do in fact solve the error threshold problem, exists. Neither has a plausible mode of protocellular sex been suggested. PMID- 1291814 TI - Control of cancer pain to ensure the best possible quality of life. PMID- 1291815 TI - Treatment of 100 cases of nerve deafness with injectio radix salviae miltiorrhizae. AB - 100 cases of nerve deafness were treated with Injectio Radix Salviae Miltiorrhizae by i.v. drip, and additional drugs that promoted blood circulation were used according to symptom differentiation. Results were 28 cases cured, 45 cases improved, and 27 cases failed, for a total effective rate of 73%. PMID- 1291816 TI - Therapeutic effect in 216 cases of acne, chloasma, and flat condyloma treated with mould-like masks containing Chinese drugs. PMID- 1291817 TI - Observations on the long-term effects of "yi qi yang yin decoction" combined with radiotherapy in the treatment of nasopharyngeal carcinoma. PMID- 1291818 TI - Treatment of fever due to exopathic wind-cold by rapid acupuncture. AB - 57 cases of common cold, influenza, acute tonsillitis and acute bronchitis were treated by rapid needling with filiform needles at Dazhui (Du 14), Fengchi (GB 13), and Quchi (LI 11). The indices for observation were first determined, and the 19 cases that manifested an axilla temperature drop of over 1 degree C after treatment and a ratio of < 0.3 of the main symptom scores after treatment were regarded as markedly effective; the 27 cases that manifested an axilla temperature drop of 0.5-1.0 degree C and a symptom score ratio of 0.3-0.6 were regarded as effective, and the 11 cases that manifested an axilla temperature drop of < 0.5 degrees C and a symptom score ratio of > 0.7 were regarded as failures. The total effective rate was 80.7%. Analysis of the individual patients indicated that the peripheral blood leucocyte and lymphocyte counts differed insignificantly after needling, while the body temperature, rate of respiration, pulse, blood pressure and acupoint temperature all dropped, with a simultaneous increase in the percentage of T-lymphocytes. The immediate effects were especially marked in fevers due to exogenous wind and cold. PMID- 1291819 TI - The clinical application of corresponding acupoints. PMID- 1291820 TI - 776 cases of pain treated with auriculopressure therapy. PMID- 1291821 TI - Computerized plotting of low skin impedance points. AB - The distribution of low skin impedance points (LSIP) was studied on 68 subjects with a computer system designed for the measurement of skin impedance. The results demonstrated that LSIPs were basically distributed along the 14 channels, the overwhelming majority located right on or within 5 mm bilaterally to their courses. LSIPs were found in the area between every two channels only in a few cases. Moreover, there was no marked natural fluctuation of skin impedance in the human body and the distribution of LSIPs was considerably stable, which could be plotted on any day in the experiment. It is clear that such particular distribution of LSIPs along channels was really a biological phenomenon, not an experimental error. However, the distribution of low skin impedance was not an uninterrupted solid line but a series of LSIPs basically along the channel course. The method used in this work was accurate, reliable and repeatable which has upgraded the measurement of LSIPs to a new level. Under certain conditions, skin impedance can be used as an objective index in channel research. PMID- 1291823 TI - Massage and acupuncture in 58 cases of superior clunial neuralgia. PMID- 1291824 TI - Prevention and treatment of rhinitis and common cold by self-massage. PMID- 1291822 TI - Studies on the luminescence of channels in rats and its law of changes with "syndromes" and treatment of acupuncture and moxibustion. AB - We previously reported the discovery of 14 channels in the human body, which possessed the biophysical property of high emission of light. In this study we found the same property on the Ren and Du channels in healthy rats. Additionally, we discovered that the luminance of the related channels in rat models with different "syndromes" varied greatly. For instance, a markedly low luminance appeared on the Du channel in animals with experimental syndrome of Yang deficiency induced by hydrocortisone; while in animals with experimental syndrome of blood deficiency caused by bleeding, an apparently low luminance occurred on the Ren channel. The intensity of the emitted light on Du and Ren channels increased after acupuncture treatment, but not significantly. This phenomenon conforms to the theory in traditional Chinese medicine that the Du channel is the "sea of Yang channels", while the Ren channel is the "sea of Yin channels". PMID- 1291825 TI - Traditional Chinese methods of health preservation (3). PMID- 1291826 TI - A survey of the treatment of traumatic paraplegia by traditional Chinese medicine. PMID- 1291827 TI - Auriculoacupuncture therapy--a traditional Chinese method of treatment. PMID- 1291828 TI - Renshen zaizao wan (restorative bolus of ginseng). PMID- 1291829 TI - The future of medicine--the doctor's role. PMID- 1291830 TI - Anticipating Annapolis 1993: an interview with Jose Martinez, M.D., Med Chi Legislative Committee chairperson. Interview by Betsy Newman. PMID- 1291831 TI - A doctor in the House. PMID- 1291832 TI - Med Chi responds to state budget crisis. PMID- 1291834 TI - The 1993 Medical and Chirurgical Faculty of Maryland state legislative directory. PMID- 1291833 TI - Utilization review: legislative history. PMID- 1291835 TI - BCBSM controversy sparks Med Chi resolution. PMID- 1291836 TI - Imaging case of the month. Abdominal pregnancy. PMID- 1291837 TI - Acoustic neuroma: summary of the NIH consensus. PMID- 1291838 TI - Ultralente and multiple shots of regular insulin. PMID- 1291839 TI - Borna disease virus: molecular analysis of a neurotropic infectious agent. PMID- 1291840 TI - Influence of a 70 kilobase virulence plasmid on the ability of Yersinia enterocolitica to survive phagocytosis in vitro. AB - During the course of infection, Yersinia enterocolitica invades tissues where macrophages and polymorphonuclear leucocytes (PMNs) constitute the first line of defence. As expression of virulence in Y. enterocolitica is governed in part by a c. 70 kilobase virulence plasmid (pYV), we investigated the influence of this plasmid on the interaction between Y. enterocolitica and phagocytes in vitro. The results showed that, irrespective of plasmid-carriage, yersiniae survived phagocytosis by macrophages and PMNs. Plasmidless Y. enterocolitica that had grown intracellularly in macrophages, however, were susceptible to killing by PMNs, whereas plasmid-bearing bacteria were resistant. In vitro cultivation of Y. enterocolitica in a Ca(2+)-deficient medium resembling that found within macrophages, did not influence the susceptibility of plasmid-bearing and plasmidless strains to killing by PMNs. These results indicate that passage through macrophages renders plasmidless strains of Y. enterocolitica susceptible to killing by PMNs. This finding may explain some of the differences in the behaviour of plasmid-bearing and plasmidless strains of Yersinia species in vivo. PMID- 1291841 TI - A 'safe-site' for Salmonella typhimurium is within splenic polymorphonuclear cells. AB - Following oral or systemic infection with Salmonella typhimurium, the focus of infection is in the liver and spleen. The majority of Salmonella surviving in the liver and spleen by 4 h post infection are already in an environment where they are largely protected from subsequent killing. Previous studies have shown that the majority of surviving Salmonella are intracellular. In the present study we sought to determine the cell type containing most of the cell-associated Salmonella liberated from the spleen. We enriched for Salmonella-containing cells by Ficoll-Hypaque separation followed by fluorescence-activated cell sorting. Approximately 85% of the total intracellular Salmonella were found in Mac-1+/J 11d+ cell fractions of the Ficoll-Hypaque band and pellet. By microscopic examination of stained cells from the sorted cell populations, it was evident that virtually all of the Salmonella were in polymorphonuclear cells (PMN). The numbers of Salmonella observed microscopically were similar in numbers to Salmonella colony forming units detected by plating. Salmonella containing PMN in the Ficoll band generally contained a single bacterium, while those from the probably less healthy cells in the Ficoll pellet generally contained several Salmonella. PMID- 1291842 TI - Effect of Haemophilus somnus on phagocytosis and hydrogen peroxide production by bovine polymorphonuclear leukocytes. AB - The interactions between bovine polymorphonuclear leukocytes (PMNs) and the bacterium Haemophilus somnus are known to be complex. In this paper, we evaluated the effect of H. somnus on PMN function using a flow cytometric (FC) technique that simultaneously determined the extent of phagocytosis and hydrogen peroxide production by PMNs, as well as using conventional techniques, such as the nitroblue tetrazolium (NBT) and chemiluminescence assays, to analyse the PMN respiratory burst. Results from the FC and chemiluminescence assays demonstrated that in vitro exposure of PMNs to logarithmically growing H. somnus reduced the respiratory burst of PMNs obtained from healthy calves. However, this reduction was not detected by the NBT assay. A decrease in phagocytosis by PMNs could also be shown using the FC assay. In addition, PMNs from calves with acute Hemophilosis (i.e. exposed to H. somnus in vivo) showed reduced activity when compared to PMNs from healthy calves. These in vitro and in vivo observations indicate that the modulation of bovine PMN function by H. somnus may contribute significantly towards the pathogenesis of the disease. PMID- 1291843 TI - The role of Haemophilus ducreyi bacteria, cytotoxin, endotoxin and antibodies in animal models for study of chancroid. AB - Haemophilus ducreyi cytotoxin-positive and -negative strains as well as bacterial sonicates and lipooligosaccharides (LOS) from such strains were evaluated for the capacity to produce dermonecrotic lesions, especially ulcers, after intradermal injections to rabbits and to different mouse strains, including nude mice. Dermonecrotic lesions of the ulcerous type were observed within 4 days and they were developed in both rabbits and mice with about 10(7) colony forming units (cfu) of H. ducreyi. Viable bacteria were isolated from the lesions up to 9 days after inoculation. All lesions healed spontaneously within 2-3 weeks. Bacterial sonicate (heated and unheated) and LOS preparations caused mainly abscess formation in rabbits, while in mice, a superficial, haemorrhagic ulceration was observed. To obtain ulceration at all injection sites, about 200 micrograms of LOS was required. Histological examination of acute, dermonecrotic lesions caused by viable bacteria showed deep necrosis, infiltrate of inflammatory cells, especially granulocytes and dilatation of blood vessels. The same type of inflammatory cells as seen in lesions caused by bacteria, were involved in the mouse lesions caused by bacterial sonicate and LOS preparations. The results indicate that LOS/endotoxin, probably in combination with other bacterial polysaccharides, can play a role in ulceration caused by H. ducreyi in animals; however, a relatively high amount of LOS preparation was necessary to cause dermal ulceration at all injection sites in the mouse model. The development of ulcers correlated with the endotoxin activity in bacterial sonicate and in LOS preparations. The model may therefore be useful to study the role of LOS components in development of ulceration. There was no significant difference in lesions caused by cytotoxin producing, respectively, non-producing H. ducreyi strains and cell-free preparations from such strains. The bacterial sonicates, cytotoxic for human cell lines, failed to kill animal cell lines, indicating that animal models do not adequately reflect the cytotoxin activity in experimental H. ducreyi infection. Antibodies to H. ducreyi sonicate and LOS, tested by means of ELISA, were found in pre-immune sera from both rabbits and mice. There was a significant antibody response to homologous cell sonicate and LOS, after primary and secondary infections with bacteria. Still, there was no clear difference between primary and secondary lesions in animals. Since animal lesions are mainly due to endotoxin activity, this may indicate that antibodies are of minor importance for protection in animal models. PMID- 1291844 TI - Cloning and nucleotide sequence of a variant Shiga-like toxin II gene from Escherichia coli OX3:H21 isolated from a case of sudden infant death syndrome. AB - Escherichia coli OX3:H21 expressing a toxin related to Shiga-like toxin (SLT) was isolated from the small bowel contents of a case of Sudden Infant Death Syndrome (SIDS). This strain was lysogenic for a lambdoid bacteriophage, but this did not encode the toxin. Southern hybridization analysis of chromosomal DNA revealed that the SLT-related gene was located on a 4.6 kb PstI fragment, which was cloned into E. coli JM109 in both orientations, using the vector pUC19, to generate plasmids pJCP501 and pJCP502. JM109 cells harbouring the recombinant plasmid produced SLT, as judged by cytotoxicity for Vero cells. Nucleotide sequence analysis revealed that the SLT gene was related to, but distinct from, previously reported variants of Shiga-like toxin type II, produced by E. coli from both human and animal sources. The A subunit of the SLT gene from OX3:H21 exhibited 95.9% homology (at both the DNA and derived amino acid sequence level) to the A subunit of the most closely related SLT-II variant. The B subunit was less similar, exhibiting 88.6 and 88.8% homology to the related gene at the DNA and amino acid level, respectively. PMID- 1291845 TI - Detection of a vascular permeability factor in the extracellular products of Renibacterium salmoninarum. AB - The presence of vascular permeability factors in the extracellular products (ECP) of 10 strains of Renibacterium salmoninarum with different geographical origin and serological characteristics are reported. All the ECP produced haemorrhagic and/or oedematous zones at the injection site with a diameter ranging from 10-30 mm. However, the ECP samples did not display toxic effect in fish at the same dose as inoculated in rabbit (180-400 micrograms protein/0.1 ml). No differences were observed in the production of this dermatotoxic factor between the two antigenic groups found in this microorganism. Whereas heating (80 and 100 degrees C/15 min) the ECP samples resulted in a complete loss of their proteolytic activity, only a decrease (but not total inactivation) of the dermatotoxic effects was detected. Therefore, although proteases could be implicated in the permeability factor, they are not totally responsible for this activity. PMID- 1291847 TI - Why do we continue to use ineffective types of care? PMID- 1291846 TI - The 17 kDa lipoprotein and encoding gene of Francisella tularensis LVS are conserved in strains of Francisella tularensis. AB - A T-cell-stimulating 17 kDa protein of the vaccine strain Francisella tularensis LVS has previously been cloned, sequenced and shown to be a lipoprotein. In the present study, it was investigated whether the protein, denoted TUL4, and its gene are present in various strains of the genus Francisella. By Western blot analysis, it was demonstrated that a TUL4-specific monoclonal antibody bound to a protein present in each of the Francisella strains. The immunoreactive proteins had an M(r) of 17 kDa in all F. tularensis strains and in the strain Francisella novicida, whereas the M(r) in strains of Francisella philomiragia was 20 kDa. When genomic preparations were probed with a radioactive DNA fragment of F. tularensis LVS encoding TUL4, hybridization was demonstrated in all strains of Francisella, although the F. philomiragia strains did not hybridize under conditions of high stringency. The hybridizing chromosomal DNA fragment of the F. philomiragia strains was larger than that of the other Francisella strains. No hybridization or Western blot reactivity was seen when various other Gram negative and Gram-positive bacteria were probed. In summary, the 17 kDa lipoprotein of F. tularensis LVS appears to be Francisella-specific and present in the species F. tularensis and F. novicida, whereas an immunologically related protein is present in F. philomiragia. PMID- 1291848 TI - The rebirth of midwifery in Canada: an historical perspective. AB - The history of midwifery in Canada, beginning in the 17th century in New France, is characterised by periods of suppression and rebirth. At present, the long standing dominance of the medical establishment is giving way to the demand of women to assume greater control over the birthing process. Several provinces in Canada are in the process of obtaining midwifery legislation designed to strengthen, support and legalise the practice of midwifery. Lack of supportive legislation has discouraged the practice of midwifery. Though midwifery care has not been readily accessible, women have persisted in their search for care by a midwife. In response, female friends with a variety of educational preparation have found ways to prepare themselves and respond to women's need for an expert in normal birth. From an historical analysis of midwifery in Canada it would appear that a primary factor influencing midwifery's rebirth has been the power and determination of women to demedicalise normal birth and return it to the domain of women. PMID- 1291849 TI - To stay or not to stay: are fears about shorter postnatal hospital stays justified? AB - Common concerns raised during a Ministerial Review of Birthing Services in Victoria, Australia about the potential detrimental effects of shorter hospital stays after birth were examined in a study of women's actual experiences of and opinions about their hospital stays. Just under one in four women left hospital within five days of the birth, with the greater majority staying five days or more. Satisfaction with length of stay was high in the sample, with 82% of women feeling their stay had been about right, 11% feeling it had been too long and only 7% of women feeling their stay had been too short. A number of the concerns about the consequences of shorter lengths of stay were not borne out. Women who left hospital earlier than the traditional 5-7 day stay were not less likely to breast feed, nor were they more likely to be depressed 8-9 months after the birth. They were also much more likely to feel confident about looking after their baby when they went home than women who stayed five days or more. Implications for further research and for policy development concerning length of stay are considered. PMID- 1291850 TI - She can lip-read, she'll be all right: improving maternity care for the deaf and hearing-impaired. AB - In the UK a midwife is unlikely to meet many deaf women during her working life. Therefore very few midwives have a wealth of experience in providing care for these women. Postnatal discussion with one woman showed us that despite our good intentions the care we had given her was inadequate for her individual needs. We recognised that other deaf women were possibly receiving inadequate care. We set out to investigate this, and when we discovered that our suspicions were correct, devised a method that we hoped would improve the care we provided. The process of investigating the needs of deaf women is described in this paper together with the development of a teaching package for student and qualified midwives. PMID- 1291851 TI - The value of clinical experience to a non-clinician: combining midwifery practice with teaching. AB - This paper explores the value of clinical experience to midwives and other health care providers who work in other than clinical situations. The value of this experience may relate to personal or educational goals. Due to the lack of attention to this topic in the midwifery literature, the author recounts her own experience and compares it with the nursing and health visiting literature. Differing expectations feature as an issue. The value of this arrangement, for teaching, research and personal development more than compensate for the difficulties identified. PMID- 1291852 TI - A simplified form of cardiotocography for antenatal fetal assessment. AB - Antenatal cardiotocography has become the primary method of evaluation of fetal wellbeing, and the relationship between the presence of fetal heart rate accelerations in response to fetal movement and subsequent good fetal outcome has been demonstrated. However, in areas where electronic monitors are few or not available it would be useful if such accelerations could be demonstrated using the Pinard stethoscope. A prospective study involving 200 women with a singleton pregnancy of more than 34 weeks gestation was performed at Harare Maternity Hospital, Harare, Zimbabwe, when a 6 min electronic trace using an external transducer was compared with simultaneously performed 6 min manual record using the Pinard stethoscope. The findings showed that the manual record has a sensitivity of 75% and although traces with excessive base line variability would show an acceleration on the manual record, in no case with a flat trace was an acceleration noted on the manual record. This acceptable degree of sensitivity would allow for a significant decrease in the number of women being referred for electronic tracing and would be a more appropriate use of limited resources in terms of manpower and equipment. PMID- 1291853 TI - Comparison of the effect of sodium fluoride and calcidiol on the rib cortical endosteal surface remodeling in dogs receiving prednisone. AB - The effects of sodium fluoride and calcidiol on the remodeling of the rib cortical-endosteal surface were compared in dogs treated with prednisone over long-term periods. In the study histomorphometric and tetracycline-labeling methods were used. It was found that administration of sodium fluoride in combination with calcidiol and calcium carbonate limited the development of prednisone-induced osteoporosis to a higher degree than treatment with calcidiol and calcium. This included less enhancement of the bone resorption surface, an increase in both the bone formation surface and osteoid seam thickness in conjunction with a lower reduction in the mineralization rate. The changes induced by sodium fluoride had a favorable effect on the ratio of the resorption to the formation processes at the basal multicellular units of bone turnover. PMID- 1291854 TI - Stimulation of renal prostanoid synthesis by potassium loading in the rat. AB - In vitro we measured the urinary excretion and synthesis of prostaglandins (PGE2, 6-keto-PGF1 alpha, thromboxane B2 and PGF2 alpha) by isolated glomeruli, cortical homogenates, medulla and papilla in KCl-loaded rats (KCl+, average K intake: 17 mmol/day for 20 days) and in rats loaded with non-Cl K salts (KCl-, average K intake: 21 mmol/day) as compared with control rats. In 2 separate groups of rats (KCl+ and KCl-) the urinary excretion of prostaglandins was measured after variations of K intake from an average of 4 to 20 mmol/day in 5-day periods. Glomerular PGE2 synthesis tended to decrease in KCl+, whereas it increased in KCl rats. 6-Keto-PGF1 alpha and TXB2 did not vary, and PGF2 alpha decreased in both K-loaded groups. In the cortex, KCl loading decreased PGE2 synthesis. In KCl-, cortical TXB2 decreased. In the medulla, KCl loading increased the synthesis of TXB2 and PGF2 alpha, but not that of PGE2 and 6-keto-PGF1 alpha. In KCl- rats, TXB2 but not PGF2 alpha increased and PGE2 synthesis was also elevated. In the papilla, TXB2 synthesis increased in both KCl+ and KCl- rats. The urinary excretion of 6-keto-PGF1 alpha and TXB2 increased in both KCl+ and KCl- rats, whereas PGF2 alpha increased only in KCl+ rats. The changes of glomerular prostaglandin synthesis during K loading could dilate the glomerular vasculature, in keeping with the known vasoactive effects of the cation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291855 TI - Platelet levels of reduced glutathione, superoxide dismutase, zinc and malondialdehyde in uremic patients. AB - Platelet-reduced glutathione (GSH), superoxide dismutase (SOD) and zinc content as well as malondialdehyde (MDA) formation were studied in 24 healthy volunteers as controls and 25 patients with chronic renal failure. Uremic patients had a significantly lower GSH and SOD content as well as an abnormal MDA formation in platelets. Their plasma zinc levels were sharply below the normal value, but the platelet zinc content was similar to normal controls. The decrease in the platelet GSH level was closely related to plasma zinc in uremic patients. We also found that the platelet zinc levels were positively correlated to the platelet GSH content in normal controls and uremic patients, but not to the platelet SOD level. The results suggest that uremic toxins may influence the content of platelet GSH and SOD, as well as inhibit prostaglandin synthesis. The decreases in platelet GSH may partially be related to the low plasma zinc level. PMID- 1291856 TI - Acute renal denervation decreases tubular phosphate reabsorption. AB - Acute renal denervation (DNX) has been reported to increase urinary phosphate (Pi) excretion in rats with intact parathyroid glands and also in rats which were thyroparathyroidectomized (TPTX). The present study was performed to determine the effects of acute renal denervation on the tubular transport of Pi in rats in the absence of parathyroid hormone (PTH) and in rats with constant PTH levels. In TPTX rats, the reabsorbed Pi normalized for the glomerular filtration rate (Reab Pi/GFR) was 2.38 +/- 0.16 mumol/ml in the DNX kidney compared to 2.56 +/- 0.16 mumol/ml (p < 0.05) in the contralateral innervated (INN) kidney at endogenous plasma phosphate levels (n = 6). The lower values for the Reab Pi/GFR in the DNX kidney persisted at elevated plasma phosphate concentrations during phosphate infusions. Infusion of PTH resulted in markedly lower Reab Pi/GFR values in the innervated kidney (1.47 +/- 0.21 mumol/ml) at endogenous plasma phosphate levels than in the vehicle-infused group. Furthermore, the Reab Pi/GFR in the DNX kidney was decreased (1.21 +/- 0.14 mumol/ml, n = 6) compared to the contralateral INN kidney. These studies demonstrate that acute renal DNX decreases the tubular transport of Pi both in the absence and in the presence of constant PTH levels. PMID- 1291857 TI - Hyperparathyroidism: cause or consequence of recurrent calcium nephrolithiasis? AB - Primary hyperparathyroidism (PHP) might be characterized by either prevailing bone or renal stone patterns with different metabolic features. To explore the possibility of different hormonal patterns we studied 129 patients with PHP: 95 stone formers (SF) and 34 nonstone formers (NSF). Females prevailed over males in both groups. Severe and specific bone lesions were more evident in NSF than SF. Parathyroid gland histology displayed a prevalence of adenoma in NSF, whereas isolated hyperplasia prevailed in SF. SF had lower levels of serum Ca, urinary Ca, ALP and serum PTH than NSF. As expected serum 1,25-dihydroxyvitamin D [1,25(OH)2 D] levels were greater in both groups of patients than in controls but we found no difference between the two groups. 25-Hydroxyvitamin D was neither increased with respect to controls nor different between groups. We conclude that patients with PHP may represent well separated metabolic and clinical entities, but we cannot confirm that serum 1,25(OH)2D levels play a key role in discriminating the different clinical features. In addition, the findings of predominant parathyroid hyperplasia in SF and the clinical evidence of recurrent hyperparathyroidism only in these patients suggest the possibility that the endocrine disorder might be the consequence over time rather than the cause of nephrolithiasis. PMID- 1291858 TI - Severe hypophosphatemia in a patient with anorexia nervosa during oral feeding. AB - We report a case of refeeding-associated hypophosphatemia in a 24-year-old malnourished male patient with anorexia nervosa but no history of alcoholism. He was given tube feeding with a low-calory preparation supplemented with phosphate. During refeeding, a severe hypophosphatemia developed after 5 days, i.e., serum phosphate 0.00-0.01 mmol/l for 2 days, accompanied by a reduction in red-cell ATP and 2,3-diphosphoglycerate, mild hemolytic anemia and transient changes in cardiac repolarization; there was, however, a striking lack of clinical symptomatology. Parenteral replacement with phosphate initially was complicated by an unexpected high urinary phosphate excretion due to an extremely low TmP/GFR (0.02 mmol/l) for over 2 days. Only after an increase of the TmP/GFR to supranormal values, i.e. up to 2.5 mmol/l, unrelated to changes in serum PTH or vitamin D3, the serum phosphate concentration became normal. The case report shows that severe hypophosphatemia can occur in nonalcoholic patients after oral feeding, and may induce reversible changes in renal phosphate handling that complicate replacement therapy. PMID- 1291859 TI - Effect of ethanol on water and chloride transport in the rat papillary collecting duct. AB - While it is believed that the effect of ethanol on human renal water homeostasis is indirect, amphibian membrane experiments have demonstrated direct effects albeit at high concentrations. To evaluate the direct effect of ethanol, diffusional water and chloride permeability was simultaneously measured in isolated rat papillary collecting ducts with increasing concentrations of ethanol (0, 0.12, 0.24, 0.48, 0.96 and 1.92 g%) both in the presence and absence of arginine vasopressin (AVP). Low concentration of ethanol (0.12 g%) increased basal water permeability by 9%. With increasing concentrations it then fell to control levels (0.48 g%) only to increase again with concentrations of 0.96 and 1.92 g% to a maximum increase of 26%. Similar changes in chloride permeability occurred. Water permeability in the presence of submaximal concentrations of AVP (20 microU/ml) was also significantly increased with lower concentrations of ethanol (0.12, 0.24 and 0.48 g%) but fell to control levels with higher concentrations. With the highest ethanol concentration (1.92 g%), submaximal AVP did not significantly increase water permeability. However water permeability was unaltered by increasing concentrations of ethanol in the presence of supramaximal AVP (2,000 microU/ml). These results demonstrate a direct effect of ethanol upon distal nephron water and chloride transport. PMID- 1291860 TI - Subdiaphragmatic vagotomy in rats induces systemic hypertension and sodium retention. AB - We examined the acute effects of bilateral subdiaphragmatic vagotomy (BSV) on blood pressure and renal function in female Sprague-Dawley rats. Mean arterial pressure was greater (p < 0.0001) in rats with BSV than in sham-operated rats (SOR). Rats with BSV had a significantly lower effective renal plasma flow (p < 0.01), total sodium excretion (p < 0.005), fractional sodium excretion (p < 0.01), urine flow (p < 0.01), and fractional excretion of water (p < 0.02) than SOR. The glomerular filtration rate was not significantly different between the 2 groups of rats. Plasma potassium was greater in rats with BSV than in SOR (p < 0.02). Pretreatment with an inhibitor of the angiotensin-converting enzyme prevented the above changes in rats with BSV. Changes in renal function and mean arterial pressure could not be attributed to antidiuretic hormone since plasma levels of antidiuretic hormone were lower in rats with BSV than in SOR (p < 0.002). In addition, the activity of the sympathetic system was decreased in rats with BSV, as suggested by the lower plasma levels of epinephrine (p < 0.003) and norepinephrine (p < 0.02) and the significantly lower renal tissue concentrations of norepinephrine (p < 0.03). No significant changes in renal tissue concentrations of acetylcholine or choline, its precursor, were observed in BSV rats when compared to SOR, suggesting a lack of renal parasympathetic innervation. Plasma renin activity was lower in rats with BSV (p < 0.02) than in SOR, but this effect was blunted in rats given an angiotensin-converting enzyme inhibitor prior to BSV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291861 TI - Acute effect of parathyroid hormone on Ca2+ ATPase of pancreatic islets. AB - The Vmax of Ca2+ ATPase of pancreatic islets is reduced in states of chronic excess of PTH. This has been attributed to the reduced ATP content of pancreatic islet and to impaired response of the enzyme to calmodulin. It is also possible that excess PTH directly inhibits the activity of islet Ca2+ ATPase. The present study examined this issue. Small doses of 1-84 PTH (0.0625 and 0.125 x 10(-7) M) stimulated while larger doses (0.25, 0.5, 1.0, 2.0 and 4.0 x 10(-7) M) inhibited the activity of Ca2+ ATPase of intact islets. PTH has no effect on Ca2+ ATPase when the hormone was added to preparation of membrane homogenate of islets. Verapamil abolished both the stimulatory as well the inhibitory effects of PTH on Ca2+ ATPase of intact islets. The data indicate that PTH does not have a direct effect on the Vmax of islet Ca2+ ATPase of islet. Its effect on the enzyme activity of intact islet is most likely mediated through the hormone-induced calcium influx. PMID- 1291863 TI - Medicare asking for copies of medical records. PMID- 1291862 TI - Luminal membrane potassium conductance of rabbit proximal straight tubules. AB - Potassium channels have been found in the apical and basolateral membranes of renal proximal straight tubules, but the fraction of apical membrane conductance due to or associated with potassium has not been reported. Therefore, the transepithelial conductance of rabbit pars recta was measured and the portion of conductance which was inhibited by barium determined. The mean control transepithelial voltage and conductance were -5.6 +/- 0.7 mV and 106 +/- 10 mS/cm2, respectively. The addition of barium to the luminal perfusing solution decreased transepithelial conductance to 93 +/- 9 mS/cm2. This decrease of 13 +/- 2% from control (p < 0.001, n = 20) cannot be explained solely by inhibition of an apical potassium conductance. It is proposed that the apical potassium channels found in the pars recta facilitate transepithelial conductive transport by sodium and other ions. PMID- 1291864 TI - Payments that Medicare is allowing. PMID- 1291865 TI - CHAMPUS guidelines for Missouri physicians. PMID- 1291866 TI - Transfusion medicine in the 1990s, why it has changed and how. AB - This paper is intended for physicians not directly responsible for transfusion medicine in their everyday practices. The field has changed dramatically in the last decade. This paper attempts to outline these changes, and detail factors that will be of practical use in general, medical, and surgical practices. Topics include available blood products with indications and risks, education about types of blood donation, possible future products, and a key concept in the field today, "conservation." PMID- 1291867 TI - Dissociation of somatosensory and motor evoked potentials in a patient with an intramedullary spinal tumor. AB - We describe a patient with an intramedullary spinal tumor who demonstrated postoperative improvement of motor and sensory function despite the lack of somatosensory evoked potentials (SSEPs) before and after intraoperative monitoring. The motor system was evaluated by direct spinal cord stimulation across the tumor bed. The resultant evoked compound muscle action potentials and compound nerve activities were normal. Although there is sufficient clinical evidence that SSEPs are sensitive to posterior and posterolateral ischemic insults of the spinal cord, the technique should be employed with an awareness of its limitations in monitoring the descending tracts which have a different blood supply and occupy more anterior locations in the spinal cord. PMID- 1291868 TI - Contemporary management of chronic persistent cough. AB - A chronic persistent cough is one that lasts longer than eight weeks in a patient without known chronic pulmonary disease. These patients may experience prolonged frustration, guilt and self-imposed social isolation, besides risking the medical and surgical complications of recurrent coughing episodes, if the cause of their cough is not quickly established and treated. A comprehensive discussion of the management approach to this problem with reference to the recent literature is presented. PMID- 1291869 TI - Venous stasis ulceration. PMID- 1291870 TI - The spectrum of opportunistic filamentous fungi present in the CBS culture collection. AB - The mould collection of the Centraalbureau voor Schimmelcultures, Baarn, The Netherlands, was screened for isolates originating from warm-blooded animals. The range of species indicates that distribution of clinically relevant, pathogenic or opportunistic strains over the fungal kingdom is non-random. Some opportunistic fungi possess adaptations to life under hostile environmental conditions, enabling them to survive inside the human body. Presence of melanin or carotene seems to be an important virulence factor. Opportunistic fungi which sporulate in submersion are able to disseminate or cause severe local mycoses when the aspecific immune system of the host is impaired. Mycoses caused by a few dimorphic fungi, mostly in their natural ecological niche living in association with vertebrates, are promoted by specific immune deficiencies. PMID- 1291871 TI - A retrospective clinical comparison between antifungal treatment with liposomal amphotericin B (AmBisome) and conventional amphotericin B in transplant recipients. AB - Invasive fungal infections are an important cause of morbidity and mortality in immunosuppressed bone marrow and solid organ transplant recipients. Treatment with amphotericin B, the drug of choice for these infections, is however often limited by toxicity. Ten transplant patients receiving a liposomal amphotericin B formulation (AmBisome) were compared to ten retrospective control patients given conventional amphotericin B. Each group included bone marrow (8), kidney (1), and liver transplant (1) recipients. Conventional amphotericin B treatment was instituted due to nine Candida infections, and one Aspergillus fumigatus infection. In the AmBisome group treatment was instituted due to eight Candida infections, one infection caused by Saccharomyces cerevisiae and in one case as prophylactic treatment. In the amphotericin B group, maximal daily doses ranged from 0.1 to 0.65 mg kg-1 and cumulative doses were 21-836 mg kg-1 and were given over 3-32 days. In the AmBisome group, maximal daily doses ranged from 0.9 to 2.3 mg kg-1 and cumulative doses ranged from 225 to 3525 mg kg-1 over 8-28 days. All patients in the amphotericin B group experienced severe toxicity, especially nephrotoxicity which in four cases caused withdrawal of the drug. In contrast, the only adverse reaction in the AmBisome group was cholestasis in one patient. Only three out of ten patients in the amphotericin B group responded to treatment, seven patients died and six patients still had evidence of invasive fungal infection at autopsy. In contrast, eight out of nine patients in the AmBisome group responded to treatment, and the patient that received prophylaxis had a successful course. PMID- 1291872 TI - Prophylaxis and treatment of fungal infections with fluconazole in bone marrow transplant patients. AB - In an open study 31 patients undergoing bone marrow transplantation for various haematological diseases received fluconazole as prophylaxis or treatment of fungal infections. In 26 of these patients an antecedent oral prophylaxis with polyene antimycotics had failed to prevent infections with Candida species. Five of the 31 patients received fluconazole as primary prophylaxis because of non compliance for polyene antimycotics. Fluconazole was administered orally at a daily dose of 100 mg and 200 mg, respectively (n = 29), or intravenously at a dose of 100 mg and 400 mg (n = 2). Cure or efficient prophylaxis was achieved in 22/31 patients (71%) after a median of 52 (9 to 493+) treatment days. In three patients (10%) Candida was eradicated but the infection reappeared 14-28 days after cessation of the drug; in 6 patients (20%) the infection was persistent or progressive. Four patients developed lethal Aspergillus infection while on fluconazole medication. A moderate and reversible elevation of liver function tests under therapy was observed in 9 patients and was possibly attributable to fluconazole in three of them (10%). One patient developed tremor which resolved after cessation of fluconazole. No other adverse drug reactions could be noted. We conclude that fluconazole is a relatively safe and effective drug for the prevention and treatment of superficial and, possibly, deep Candida infections in severely immunocompromised patients. However, it is presumably without preventive value in Aspergillus infections. PMID- 1291873 TI - Fungal infections in surgical patients. AB - Deep fungal infection was diagnosed in 42 patients (a rate of four per 1000) treated during a one-year period between 1988 and 1989 at the Surgical Clinic in Wurzburg. Most occurred in association with damage to intra-abdominal hollow organs. Diagnosis of deep fungal infections is difficult and only histological identification provides definite proof. However, often the decision to treat has to be made on the basis of the clinical picture and the physician's subjective assessment. Combination treatment with amphotericin B and 5-fluorocytosine is still the current recommendation but the introduction of the azole antifungal agents appears likely to bring about a change. A trial of fluconazole showed it to have clear advantages over combination treatment, being effective, well tolerated and easily administered. PMID- 1291874 TI - Vaginal yeast flora of pregnant women in the Cusco region of Peru. AB - A study of the vaginal yeast flora in pregnant women living in Cusco and in its region (Peru), located approximately 3000 m above sea level, is reported. We observed 300 pregnant, healthy and non-diabetic women who attended a gynaecological clinic in the Lorena, Regional or IPSS (Instituto Peruano de Seguridad Social) hospitals in Cusco. A comprehensive clinical history was obtained from each patient. It included age, work, parity, time of pregnancy, use of contraceptives or antibiotics, type of vaginal symptoms, type and amount of vaginal secretion. The yeasts were isolated from 44.3% of the cases. The positive cases were more frequently found in the following categories: 20-30 year-old patients (69.2%), ninth month of pregnancy (49.6%), first pregnancy (41.4%), no delivery (58.7%) and no abortion (66.9%). Most women complained of leukorrhea (75.9%) with mucus, scarce without odour (18.8%) or lumpy, regular, without odour (15.8%) secretion. The yeasts isolated were Candida albicans (66.2%), other Candida species (12.8%), Torulopsis glabrata (8.3%) or other Torulopsis species (2.2%), Saccharomyces cerevisiae (7.5%), Rhodotorula sp. (1.5%) and Trichosporon cutaneum (1.5%). PMID- 1291876 TI - Cutaneous phaeohyphomycosis due to Cladosporium cladosporioides. AB - A 54-year-old man, affected by pemphigus vulgaris and severe steroid-induced diabetes, developed seven red-brown, firm, slightly raised 0.1-1 cm papular lesions on the anterior aspect of both knees and thighs. A cutaneous biopsy showed a granulomatous infiltrate with numerous fungal elements scattered in the dermis and also within giant cells. Cultures of cutaneous biopsy fragments on Sabouraud glucose agar in presence of chloramphenicol resulted in the growth of dark-green colonies at 25 degrees C. They were identified as typical Cladosporium cladosporioides. As far as we know, this species was previously isolated only in an HIV-seropositive patient as opportunistic pathogen in the site of skin testing. PMID- 1291875 TI - Immunogenic potential of Aspergillus nidulans subcellular fractions and their polypeptide components. AB - Cell-free extracts of the ascomycetous fungus Aspergillus nidulans were separated into three subcellular fractions: cell walls, total membranes and cytosol, and two different immunization protocols were used to raise antibodies against them in 12 New Zealand rabbits. The immune response was followed over time by dot and Western blot analyses to determine the immunogenic potential of each individual fraction and their polypeptide components. The IgG fractions, purified from pools of the best sera, were used to analyze in detail the antigenic composition of A. nidulans mycelium. The fast immunization protocol provided a much earlier response and higher sera titres. Cytosols and membranes were more immunogenic than cell walls and, in most cases, a positive correlation was shown between the titre of each serum and the number of detected antigens. The polypeptides of A. nidulans included six major immunodominant antigens of the molecular weights ranging between 13 and 200 kDa. PMID- 1291877 TI - Demonstration of antibodies against Candida guilliermondii var. guilliermondii in asymptomatic infertile men. AB - Candida guilliermondii (C.g.) occurs mostly in animals, but it can affect humans too. Using serological screening methods studies have been carried out in 57 (30 normozoospermic and 27 oligozoospermic) asymptomatic infertile men, of whom 15 (26.3%; 9 oligozoospermic and 6 normozoospermic) were found to have responded to Candida guilliermondii var. guilliermondii. Sperm parameters (cell count, motility, morphology) were determined and various tests (hypo-osmotic swelling test, bovine mucus penetration, swim-up and testosterone examinations) were also performed. In the C.g.-infected and non-infected groups no significant difference was observed in any of the parameters. Precipitation was performed with a special antigen and in the positive group agglutination titres ranged from 0 to 1/320. Comparing C.g. titres with sperm parameters, only the swim-up technique showed noticeable alteration (P = 0.003). One month following ketoconazole treatment, the patients showed no precipitation reactions and their agglutination titres were < 1/80. Our results suggest that for the diagnosis of male infertility a serologic screening for C.g. is essential. As C.g. can also be sexually transmitted, both the husband and wife must be treated, if infection occurs. PMID- 1291878 TI - Outdoor airborne dermatophytes and related fungi: a survey in Turin (Italy). AB - Aerial dispersal of propagules, an important mechanism of fungal spread, has not been sufficiently studied for skin-infecting fungi. Over a period of one year, we have monitored the distribution of dermatophytes in the air of Turin. We have also examined the related aleurioconidic and arthroconidic fungi, which share physiological and morphological characters with dermatophytes and are sometimes considered to cause similar infections. A viable volumetric collector was used. Samples were taken each month; each sample collected 9.6 m3 of air. The medium was Dermasel agar supplemented with cycloheximide and chloramphenicol. Thirty-two species were isolated, within the genera Aphanoascus, Arthrographis, Chrysosporium, Geomyces, Gymnoascus, Malbranchea, Myceliophthora, Myxotrichum, Ovadendron, Trichophyton. The total mycoflora load obtained was rather low throughout the year and particularly in the hottest months. Apart from T. rubrum and T. mentagrophytes, which are dermatophytes very frequently encountered in Turin, many of the species detected have known pathogenic potential and/or keratinolytic activity. PMID- 1291879 TI - Incidence of febrile seizures in The Netherlands. AB - To assess the incidence of febrile seizures in The Netherlands, we analyzed data from a population-based study carried out in 161 Dutch general practices. The overall incidence rate was 4.8/1,000 person-years. Considerable age and seasonal variation was found. The chance of a child suffering a febrile seizure in the course of the relevant age period (3-72 months) is 2.7%. One out of 3 children was referred to hospital. This is considerably less than in other countries. The incidence rates are similar to those found in the United States, England and Sweden, but differ from Asian studies. PMID- 1291880 TI - Correlates of hot water epilepsy in rural south India: a descriptive study. AB - Seizures precipitated by the stimulus of hot water known as 'hot water epilepsy' (HWE) have been commonly reported from South India. The present report outlines certain descriptive epidemiological aspects of 78 cases from two rural satellite clinics of National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India. Geographical clustering was observed in one of the centres. HWE was common in the age group of 26-35 years with a male to female ratio of 3.6:1. The frequency of seizure occurrence was more than 1-4 attacks/month in 89% of cases. Past history of febrile convulsions and family history of HWE was noticed in 27 and 18% of our cases, respectively. The conversion of reflex to nonreflex epilepsy occurred in 30.8% of cases. Population-based epidemiological studies are essential for further understanding of HWE for developing strategies towards prevention and control. PMID- 1291881 TI - Effects of epilepsy on daily functioning in northern Ecuador: summary of findings of a population-based research project. AB - 215 patients with epilepsy and 125 healthy controls were questioned on the effects of epilepsy on social functioning as part of a population-based study of epilepsy in Northern Ecuador. 144 of these patients and 98 of the controls were followed, over a period of 1 year during an intervention study and their response to treatment assessed. Economic, intellectual and social functioning were examined. In the patient group, function was affected in important areas, most clearly, work. The low opinion the community had of the intellectual and physical abilities of patients might affect a patient's own view of themselves and sometimes diminish their opportunity for development. At 12 months, as a result of treatment, a significantly lower level of patients reported effects on function in some areas, though control individuals' views of their functional impairment had not shifted to any extent. Moreover, despite improvement, more patients at 12 months acknowledged fear of seizures, especially their unpredictability, as a handicapping factor, particularly in working outside or away from home. This seems to indicate that even when seizures are controlled, for many patients, the uncertainties of the condition remain and continue to affect their view of their capabilities. PMID- 1291882 TI - Stroke subtype is an age-independent predictor of first-year survival. AB - The short-term outcome after acute stroke is known to be strongly dependent on stroke subtype, especially favoring patients having suffered a lacunar stroke. The value of stroke subtypes as long-term predictors of survival has not been firmly established. We therefore examined the 1-year survival from acute stroke in the Klosterneuburg Stroke Data Bank, which since 1988 systematically collects data on acute stroke patients treated in one center in Lower Austria. The cumulative survival of 398 consecutive patients (mean age 67.7 +/- SD 11.6) 1 year after a first-ever stroke was not only adversely related to age but also appeared to be age independent when compared according to stroke subtypes. The cumulative survival rates (CSR) ranged from 88.7 [95% confidence interval (CI): 82-92] for lacunar strokes (n = 107) to 68.1 (CI: 50-79) for atherothrombotic strokes (n = 69). Cardiogenic embolism (n = 68) showed a CSR of 72.1 (CI: 61-83) similar to the group of cryptogenic strokes (n = 121, CSR: 74.4, CI: 67-82). The CSR for primary intracerebral hemorrhage (n = 33) was 68.8 (CI: 53-85). It is concluded that the comparatively favorable prognosis of lacunar strokes must be recognized in trials designed to evaluate efficacy in terms of 1-year mortality. Furthermore, as cryptogenic stroke has an almost identical survival rate when compared to strokes caused by cardiogenic embolism it may be assumed that a considerable number of strokes for which no cause can be found are, in fact, cardiogenic embolic. PMID- 1291883 TI - Update of trends in mortality from stroke in Italy from 1955 to 1987. AB - Mortality form stroke in Italy over the period 1955-1987 was analysed in terms of age-specific, age-standardised death certification rates, and by means of a log linear model to separate the effects of age, cohort of birth and calendar period of death. In males the overall age-adjusted rate on the world standard population fell from 118.4/100,000 population in 1955-1959 to 72.0 in 1985-1987 and in females from 94.8 in 1955-1959 to 54.7 in 1985-1987. The overall decline in age standardised rates over the 3 decades was thus 39% for males (averaging 1.7%/year) and 42% for females (averaging 1.9%/year). The declines were even greater in truncated rates from 35 to 64 years: from 80.4 to 41.2/100,000 for males (49%), and from 63.0 to 24.1/100,000 for females (62%). Inspection of age specific rates shows comparable falls--in relative terms--in early and later middle age. For instance, male rates declined from 70.4 to 38.1/100,000 (46%) at age 50-54, and from 1,151.1 to 584.2/100,000 (50%) at age 70-74. Only above age 75 were the falls smaller. In females aged 50-54 years the decline was 63%, and for those aged 70-74 years it was 59%. In young adults, no appreciable changes were observed in either sex. Thus, the age, period and cohort model showed downwards trends in both the period and cohort effect, except for the most recent cohorts on account of an age-cohort interaction. These favourable trends are discussed in relation to better control of hypertension and the potential impact of other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1291884 TI - Measuring stroke in the population: quality of routine statistics in comparison with a population-based stroke registry. AB - The validity of routine stroke data (official mortality statistics and hospital discharge registries) and a population-based MONICA stroke registry was assessed in a population of 309,806 25- to 74-year-old people in Sweden. The 'true' number of strokes in the population was estimated by screening for non-stroke diagnoses in death certificates and hospital discharge records and by a period of intensified search for otherwise unrecognized non-hospitalized stroke cases. Applying strict stroke criteria, the proportion of false-positive diagnoses was 10% and false-negative 17% in official mortality statistics. Among patients discharged alive from hospital, there were 32% false-positive and 6% false negative stroke diagnoses. In the MONICA registry, the proportion of false negative cases was 6% in fatal cases and 4% in non-fatal cases. Diagnostic information for subtyping stroke improved over time in non-fatal cases but remained essentially unchanged in fatal cases. We conclude that official mortality statistics give a reasonably good estimate of fatal stroke cases in Sweden, whereas hospital discharge records reflect poorly the incidence of stroke in the population. The overall quality of the population-based MONICA registry is good, although 4% of all strokes are missed. The proportion of unspecified stroke is substantial and changes over time; this makes longitudinal studies of stroke subtype difficult. PMID- 1291885 TI - Dietary fat in the epidemiology of multiple sclerosis: has the situation been adequately assessed? AB - Epidemiological studies have demonstrated that environmental influences contribute to determining the risk of multiple sclerosis (MS). The nature of this influence has not been established, although infectious agents have received the most attention with relative neglect of alternative hypotheses. This paper critically reviews the evidence implicating dietary fat in altering susceptibility to MS. It is concluded that a dietary theory accords with current knowledge regarding MS as well as an infective theory and thus should not be dismissed in research examining the aetiology of MS. PMID- 1291886 TI - Epidemiology of multiple sclerosis in US veterans. 4. Age at onset. AB - Age at onset of multiple sclerosis (MS) symptoms was ascertained for subsets of some 4,400 veterans of World War II who had been adjudged 'service-connected' for this condition. Average age at onset was 27.0 years for white men, 27.7 for white women, and 27.5 for black men. The unexpectedly older age for women is attributed to their older age at entry into service. When the coterminous United States was divided into three horizontal tiers of states, we found a strong effect of geography on age at onset. By state of residence at entry into active duty (EAD), white men had an average age at onset of 26.4 years in the northern tier, 27.3 years in the middle, and 28.8 years in the south. Trends were similar for white women and black men. Migrants, defined as those whose birth and EAD tiers differed, showed increasing ages at onset with southward moves. A statistical model used to discriminate between the influence of birth and EAD tiers on age at onset confirmed the significant effect of EAD alone. These data are compatible with the theses that the cause of MS is less common (or less efficient) in locations where the clinical disease is less common, and that its acquisition therefore occurs at an older age in those locales. PMID- 1291887 TI - The changing mortality from motor neurone disease and multiple sclerosis in England and Wales and the Republic of Ireland. AB - A study has been undertaken to ascertain the changes in mortality from motor neurone disease (MND) and from multiple sclerosis (MS) in England and Wales and in the Republic of Ireland. During the 20 years 1968-1987, 16,077 deaths were reported as being primarily due to MND in England and Wales with a male/female ratio of 1.22. There has been an increase in MND deaths from 3,185 in 1968-1972 to 5,241 in 1983-1987. The increase occurred in the death rates in both sexes and in all age groups, but particularly over the age of 65. In contrast, there was no increase in MS deaths and the MS death rates fell below the age of 55 but increased over this age, evidence that MS patients are living longer. A similar but more marked increase in MND mortality, and a considerable fall in MS mortality, occurred in the Republic of Ireland. The increase in MND mortality is not due to an increase in the number of neurologists, as there has been little increase in their numbers. The highest MND mortality was in Social Class IIIN males - skilled non-manual workers. PMID- 1291888 TI - Multiple sclerosis and prostate cancer: what do their similar geographies suggest? AB - Mortality rates from multiple sclerosis show a well-known north-south gradient, both within the United States and internationally. Mortality rates from prostate cancer show a similar gradient and are significantly correlated with multiple sclerosis (MS) mortality and MS prevalence. This finding adds prostate cancer to the set of diseases whose geographic distributions are significantly correlated with MS and whose members include colon cancer, dental caries, and Parkinson's disease. Review of the literature indicates that these clinically dissimilar diseases may share an aberration in vitamin (hormone) D. Recent evidence demonstrating a multi-faceted role for vitamin D in immunoregulation suggests that a vitamin D aberration may also contribute to the etiology of MS. A vitamin D hypothesis can illuminate several unexplained features of the epidemiology of MS and suggests opportunities for epidemiologic, laboratory, and clinical investigation. PMID- 1291889 TI - Meta-analysis of progestin and estrogen receptors in human meningiomas. AB - Among 301 human meningiomas published in the literature, 69% were progestin receptor (PgR)-positive. Estrogen receptors (ER) were detected in only 13% of the samples. The PgR levels were also elevated (p < 0.001) compared to the ER concentration. No association with sex, age, menstrual status or tumor location was found. Meningiomas with typical histology (75/171), were PgR-positive in significantly greater proportion than the atypical (12/171) or transitional (27/171) tumors. The PgR levels in the typical meningiomas were also increased (p = 0.005) compared to the atypical or transitional meningiomas. The ER levels did not differ by histology. The association of PgR levels with different histologic types is not well documented in the literature. Such an association is important for the understanding of the natural history of this disease as well as in the design and evaluation of therapeutic trials. PMID- 1291890 TI - The Neuro-Oncology Register. AB - In this report we describe the establishment of a Neuro-Oncology Register (NOR) at the University Hospital of Maastricht, The Netherlands. The register includes data on numbers and types of primary central nervous system (CNS) tumours and neurological complications of systemic cancer. One of the objectives of the register is to determine the incidence rate of neuro-oncological complications in systemic tumours and the incidence and prevalence rates of primary CNS tumours in a well-defined population. The catchment area of the NOR was defined with the help of the Dutch Regional Cancer Register. It involves 140,819 inhabitants and will be considered as our catchment population. At present, 1,168 cases have been recorded since the NOR became operational. All neuro-oncological reports in 1988 were chosen for further analysis (n = 276). We diagnosed 79 metastatic complications from systemic cancer. Metastasis of the brain is the most frequent metastatic complication in our population, followed by epidural metastasis. As in other series, the lung and breast are the most frequently encountered tumour sites. The NOR is a clinically based register which, in co-operation with the Dutch Regional Cancer Register, will generate important epidemiological data on CNS complications. PMID- 1291891 TI - A perceived cluster of amyotrophic lateral sclerosis cases in a Massachusetts community. AB - We investigated a report of a perceived cluster of amyotrophic lateral sclerosis (ALS) in Middleborough, Mass. Although an increase in ALS incidence was observed [2.51 deaths/100,000 person-years (p-y)], relative to the statewide rate over the years 1969-1985 (1.26/100,000 p-y), it was not statistically significant at the 95% confidence level. Problems in evaluating possible neurological disease clusters and their association with environmental exposures are presented. PMID- 1291892 TI - Elevated ratio of late measles among subacute sclerosing panencephalitis patients in Karachi, Pakistan. AB - Subacute sclerosing panencephalitis (SSPE) in Western countries and Japan is found more often in early- than in late-measles sufferers. Recent SSPE findings in Karachi, however, present a different picture. Age at measles contraction was obtained and analyzed for 44 SSPE patients identified in Karachi between 1983 and 1988. The ratios of early- (< 2 years of age) and late- (> or = 2 years of age) measles sufferers among 36 of these patients who had experienced only one attack of measles were 0.33 and 0.67, respectively. This is in striking contrast to the predominance of early measles in the SSPE histories reported in Japan and an number of Western countries. PMID- 1291893 TI - Validation of the Hodkinson abbreviated mental test as a screening instrument for dementia in an Italian population. AB - We investigated the accuracy of the Hodkinson abbreviated mental test (AMT) as a screening instrument for dementia in an Italian population. The AMT was administered by nonmedical personnel to 124 subjects > 59 years old. Each subject independently underwent a clinical evaluation for dementia (DSM-III criteria), and scores on the AMT were compared to corresponding clinical diagnoses (standard for comparison). Twenty of the 124 subjects were found to be affected by dementia upon clinical investigation. Although a score of 6 on the AMT showed the best combination of sensitivity (90%) and specificity (89%), only a score of 7 yielded 100% sensitivity (71% specificity). Specificity was higher in men, younger, and more educated subjects. PMID- 1291894 TI - A new type of epidemiological study: questionnaire administered by medical personnel. AB - Doctors, nurses, and medical and nursing students administered a questionnaire on memory disturbances, tremor and clumsiness in their first-degree relatives who live or lived near them. We obtained data on 1,479 relatives, of whom 805 were alive and 674 had died. Of those alive and older than 65, 8.69% had severe memory disturbances, 1.11% a parkinsonian syndrome and 5.59% essential tremor. Of those who had died, 10.68% had suffered from severe memory disturbances before they died. The results of both groups are similar and in accordance with the data in the literature. In our opinion this new type of epidemiological study can be very useful in diseases which are easily detected by nonspecialists and in areas with hospitals and medical schools. PMID- 1291895 TI - Correlation between milk and dairy product consumption and multiple sclerosis prevalence: a worldwide study. AB - Multiple sclerosis (MS) epidemiology suggests that different factors are involved in the clinical expression of the disease. Alimentary cofactors have already been considered, but mainly theoretically. We have studied the relationship between MS prevalence and dairy product consumption in 27 countries and 29 populations all over the world, with Spearman's correlation test. A good correlation between liquid cow milk and MS prevalence (rho = 0.836) was found; this correlation was highly significant (p < 0.001). A low but still significant correlation was obtained with cream or butter consumption (rho = 0.619 and rho = 0.504, respectively). No correlation was found for cheese. These results suggest that liquid cow milk could contain factor(s) - no longer present in the processed milk - influencing the clinical appearance of MS. The possible role of some dairy by products is discussed in the light of a multifactorial etiology of MS. PMID- 1291896 TI - A case-control study to evaluate the association of epilepsy and migraine. PMID- 1291897 TI - [Demonstration of cardiac arrhythmias in multi-infarct dementia and ischemic stroke using Holter monitoring]. AB - The occurrence of the cardiac arrhythmias was estimated by using 24-hour ECG Holter monitoring in 30 patients with multi-infarct dementia and in 30 with ischaemic stroke. Holter monitoring revealed pathological cardiac arrhythmias in 36.7% patients with multi-infarct dementia and in 40% with single ischaemic focus in the brain. It also allowed to reveal more frequent occurrence of cardiac arrhythmias in patients with ischaemic stroke (40%), than standard ECG (17%). PMID- 1291898 TI - [Phenotype characteristics of mononuclears in peripheral blood and csf in multiple sclerosis]. AB - In 48 clinically definite cases of multiple sclerosis the studies were performed of mononuclears phenotypes in CSF and peripheral blood. The results lead to following conclusions: 1. The percentage of cells with dominant reactivity of Anti HLADR, CD14 and CD56 in CSF is markedly lower than in the peripheral blood. 2. There exists a marked difference in the percentage of cells in CSF with reactivity anti-HLADR, CD14 and CD56 between patients in the relapse-remitting and chronic progressive phases of multiple sclerosis. PMID- 1291899 TI - [Long-term steroid therapy in multiple sclerosis]. AB - Corticosteroids have a firm place in the treatment of ms, but as yet no generally accepted regimen of this therapy exists. It is not known either, how to achieve the greatest effectiveness of these drugs and avoid side effects. Many clinicians advocate high intravenous doses of methylprednisolone in a short time of 5-7 days. This method is more effective and leads to less adverse effects. The studied patients received prednisone (Encorton Polfa) in short course of 3 days every month. The dose of Encorton in each course depended on the clinical condition but never exceeded 200 mg. The regimen was used in 18 patients who were followed up at least one year. Evident improvement or stabilization was obtained in 11 cases. No adverse effects were noted. These results are comparable to those achieved with methylprednisolone. It may be supposed that every regimen of corticoid treatment in ms is usefull if it causes no adverse effects. The treatment by method of long-term pulse therapy with corticoids is applicable in outpatients. PMID- 1291900 TI - [Hospitalization of patients with central nervous system neoplasms in 1979-1981 and 1986-1988]. AB - The hospitalizations and hospital deaths due to nervous system tumours were analysed on the basis of statistical cards filled in hospitals in a random sample of 10% of patients hospitalized in all Polish hospitals in the years 1979-1981 and 1986-1988. An evident rise was observed in the frequency of these hospitalizations and a less evident rise in the number of hospital deaths with a decrease of the hospital deaths caused by nervous system tumours. In the analysed time periods the greatest number of hospitalizations was in the age group 40-59 years, and deaths in the age group over 60 years. Hospitalization and hospital deaths indices were higher for urban population and males. PMID- 1291901 TI - [Hospitalization of patients with cerebrovascular diseases in Poland in 1979-1981 and 1986-88]. AB - Hospitalization and death indices of patients admitted with cerebrovascular diseases were analysed on the basis of statistical cards filled by hospitals in a sample of 10% in patients in all Polish hospitals in the years 1979-1981 and 1986 1988. In these years a 40% rise was noted of the hospitalization indices and a 22% rise in the death rated caused by these diseases. On the other hand, the hospital death rate decreased from 32.2% to 27.9%. Higher hospitalization indices were found for males and for the urban population. The death rates and intrahospital mortality were higher for women but the standardized death rates, with the exception of oldest age group, were higher for men. A cause for concern is the rise of hospitalization indices for men and women and death rates in men aged 40-59 years which may indicate lowering of the age of threatening stroke. PMID- 1291902 TI - [First-hand experiences in trans-sylvian microsurgery of the posterior part of the circulus arteriosus and end-part of the basilar artery]. AB - The authors present the technique and the obtained results of surgical treatment of vascular malformations in the upper part of the basilar artery in 14 patients using a trans-sylvian microsurgical approach. The techniques of subfrontal and subtemporal approaches are compared. PMID- 1291903 TI - [Treatment of cerebral vein aneurysms in children]. AB - Aneurysms of the vein of Galen are very rare vascular anomalies found mainly in newborns and infants. In the years 1982-1989 five children with these aneurysms were treated. Their age was from 6 weeks to 16 months, all were males. The diagnosis was based on computed tomography (initial examination) and cerebral angiography. Two cases with hydrocephalus were treated with valves. The main procedure was clipping of supplying vessels. One child died during diagnostic procedures. The results in four operated on patients are good. PMID- 1291904 TI - [Tumor metastases to the brain. Clinical differences]. AB - The authors analysed differences between two types of clinical diseases based on 161 cases of brain metastases. The first type (A) is, when symptoms of brain metastasis appear in different time of recognized malignant disease. In type B brain metastasis is the first symptom of neoplastic disease. PMID- 1291905 TI - [Usefulness of intracranial pressure measurement by Camino V420 system: preliminary report]. AB - The authors discuss the basis of ICP measurements with Camino V420 system and present the introductory experience of Department of Neurosurgery, Medical Academy of Lodz with it's clinical use. Continuous ICP measurements, lasting from 24h to 15 days were performed in 16 patients. In 13 of them ICP measurements were done in order to establish the dynamics of hydrocephalus and indications for shunt surgery. The other 3 suffered from intracranial hypertension, caused by trauma (1 patient) or spontaneous intracranial haemorrhage (2 patients). Camino system proved to be easy in handling, highly reliable, and infallible, even for successive days. PMID- 1291907 TI - [Changes of visual evoked potentials in experimental occlusion of superior sagittal sinus in the cat]. AB - In the model of experimental occlusion of superior sagittal sinus (SSS) in 6 cats, the authors examined cerebral cortex activity by means of visual evoked potentials (VEP). They found shortening of latency of P2 wave potential in relation to the control by 5.5-13.3 msec, appearing after 4-6 hours following occlusion. Simultaneous cerebrospinal fluid pressure measurement indicated an increase in pressure following SSS occlusion from the control medium value 6.8 mmHg to 12-13 mmHg. Visual cortex in cat (area 17) is situated along the posterior portion of SSS. The occlusion of this vessel results in local haemostasis, which is likely to affect the physico-chemical properties of visual cortex cells, especially in the slow conducting system X (X cells can be found exclusively in area 17). The partial disappearance of this system activity results in reducing the signal and noticeable shortening of latency to peak P2 wave of VEP. PMID- 1291906 TI - [Application of physiological data in evaluation of the intracranial volume pressure interaction. I. An experimental study]. AB - In experimental studies on cats the pressure and volume loadings corresponding to the physiological situations were used. The following tests were applied: central venous pressure increase, postural changes and increase of CO2 percentage in inspired gas mixture. It was found that the central venous pressure increase test is useful in the evaluation of CSF outflow routes, the postural change test examines the intracranial compensation and the elevation of CO2 level in inspired air tests the intracranial volume reserve. PMID- 1291909 TI - [A case of Alzheimer's disease simulating Creutzfeldt-Jakob disease]. AB - A case of Alzheimer's disease simulating Creutzfeldt-Jakob disease--We report here a case of 67-year old man with frank dementia accompanied by extrapyramidal syndrome and myoclonic jerks. The diagnosis of Creutzfeldt-Jakob disease was suggested but the neuropathological examination revealed features most compatible with Alzheimer's disease. The "gray area" between both cerebral amyloidoses was discussed. PMID- 1291908 TI - [Gangliosides in neurological pharmacotherapy]. AB - Gangliosides take part in synaptic transmission, neuronal metabolism and development of nervous tissue. They cooperate with nerve growth factor (NGF) and have positive influence on regeneration of the nervous system impairments. There exist many behavioural and biochemical evidences of gangliosides participation in the regeneration of experimentally injured animal nervous system. The therapeutic effectivity of gangliosides in clinical practice is encouraging. Commercial preparates of gangliosides (Cronassial, Sygen) have been successfully used in the therapy of chronic neuropathies, strokes and subarachnoidal haemorrhages. Among the adverse reactions to these drugs are: local irritation, anxiety and possible detrimental effect in immunological system. Ganglioside preparations need further clinical examinations. PMID- 1291910 TI - [Subacute sclerosing panencephalitis pregnancy]. AB - In a patient aged 16 behaviour at changes, followed by visual agnosia, aphasia, paraparesis and involuntary movements developed about the 24th week of pregnancy. The presence of measles virus antibodies in the cerebrospinal fluid and progressing course of the disease with fever suggested SSPE. Pregnancy was terminated by caesarean section in the 30th week of pregnancy, the male premature baby died after 4 days, his brain was not examined under microscope. The mother died 2 weeks after labour in decerebrate rigidity. In the brain numerous profuse infiltrations composed of lymphocytes and plasma cells were found around blood vessels, the glia was proliferated and hypertrophied, eosinophilic inclusions were demonstrated in the nucleic of cortical neurons. The authors review the very few case, reported as yet, of SSPE in pregnant women. During pregnancy natural immunosuppression occurs, which may lead to activation of dormant infection with measles virus mutant. However, the history of one of the published cases suggests the possibility of other pathogenetic factors active in such cases. PMID- 1291911 TI - [Diagnostic difficulties in tumours of foramen occipitale magnum]. AB - The reported case was diagnosed formerly as multiple sclerosis. On autopsy it was found that disseminated neurological symptoms were caused by a neurofibroma of the foramen magnum. The diagnostic difficulties in cases of tumours in this location are discussed. PMID- 1291912 TI - [A case of progressive bulbar paralysis in a child (Fazio-Londe disease)]. AB - The reported case was diagnosed in a girl aged 14, in whom the first signs developed at the age of 6, with progressive involvement of the cranial nerves IX, X, XI and XII, and V with VII. After ruling out other possible causes the diagnosis of the Fazio-Londe disease was established. Electromyographic examination confirming the diagnosis demonstrated also evidence of changes of neurogenic type in the muscles of upper extremities despite absence of demonstrable clinical abnormalities, which, as suggest the authors, may support the hypothesis of the similarity of the disease to other forms of spinal muscular atrophy, such as Werdnig-Hoffman and Kugelberg-Welander diseases. PMID- 1291913 TI - [Micropsia in multiple sclerosis]. AB - Micropsia is described in a case of remitting multiple sclerosis with left optic neuritis and spastic paraparesis. The damage to small axons in the optic nerve conducting spatial impulses from temporal and lower segments of retina might be responsible for the occurrence of transient micropsia. PMID- 1291914 TI - [Spontaneous chronic spinal epidural haematoma in a 14-year-old boy. Case report]. AB - An unusual case of a 14-year-old boy with spontaneous chronic spinal epidural haematoma treated surgically with full success is reported. The clinical presentation and aetiology are discussed. The result of treatment depends mainly on the time of duration of neurological deficit. Immediate transfer to neurosurgical department gives a chance of good recovery. PMID- 1291915 TI - [Parkinsonism caused by bilateral subdural haematomas]. AB - The authors present a case of 75-year old man with bilateral chronic subdural haematomas presenting as parkinsonism. Surgical removal haematomas was followed by complete recovery of the patient. PMID- 1291917 TI - [Report on the conference "New Trends and Advances in the Rehabilitation of Patients with Hemiparesis]. PMID- 1291916 TI - [Neurological diseases as the causes of disability]. PMID- 1291918 TI - [Top performance for cardiovascular implants in the cardiac implant market]. PMID- 1291919 TI - [The electrocardiogram in epidemiology: the Minnesota code]. AB - A correct methodological approach to electrocardiogram interpretation is an important requirement above all as far as epidemiological studies on large case reports are concerned. The Minnesota code represents a pattern of objective classification of the electrocardiogram and it is fit for application to studies on people and consequent statistical analysis. It consists of a series of items which are assembled in nine principal classes, each of them describing with objectivity a figure of the electrocardiogram; moreover it includes several classes for the codification of the electrocardiogram after effort and in sequenced studies. Multiple applications in this sense confirm the validity of this code which gains, in times of automatisation, a new value. PMID- 1291920 TI - [Physiopathology of venous stasis at the microcirculation level]. AB - The division of the venous circulation in to two sectors, one constituted by the superficial and deep venous trunks (macrocirculation) and the other by the capillaries and precapillary venules (microcirculation), is surely schematical but aids the comprehension of many hemodynamic effects connected to hampered venous return and to the incompetence of the valvular devices. In fact many of the effects of stasis and venous hypertension (oedema, red cell diapedesis, skin dystrophies) cannot be explained merely by hydraulic mechanisms but require a primary alteration of the microvascular wall associated with structural changes of the perivascular connective tissue. The alterations that occur in microcirculation are of the utmost importance in the formation of the venules ulcerations. The passage of fibrinogen through large pores in the venules of the patients affected by venous hypertension derived from venous insufficiency creates a pericapillary fibrin deposition that cannot be removed because of inadequate blood and tissue fibrinolysis. This accumulation acts as a barrier to the diffusion of oxygen and other nutrients, determining a stasis dermatitis that may lead to tissue necrosis and ulceration. The more precise knowledge of the phenomena connected with the venous stasis at the level of microcirculation (pericapillary fibrin deposition, endothelial ischemia, blocked lymphatic drainage) will not only allow a deeper comprehension of the clinical signs but hopefully will lead to a more effective treatment of the postphlebitic syndrome. PMID- 1291921 TI - [The choice of approach in the surgical therapy of the superior thoracic outlet syndrome]. AB - The symptoms of thoracic outlet syndrome (TOS) may be improved or cured either by physiotherapy or by a surgical operation. The choice of patients to be submitted to surgery must be performed on the basis of clinical picture and of non invasive and invasive assessment. Moreover the surgeon must choose the best procedure to relieve symptoms. The Authors on the basis of their experience and of a literature review refer to the various surgical approaches used in the treatment of TOS. PMID- 1291922 TI - [Profundaplasty as the only revascularization procedure in ischemia of the leg. Clinical contribution]. AB - The profunda femoris artery is the primary source of collateral flow to the lower extremity in the presence of superficial femoral and/or popliteal occlusion. The arteriosclerotic disease involvement of this segment is relatively less frequent and in the majority of the cases localized on the ostium and reaches to the first branch. Profundaplasty to relieve limb-threatening ischemia is infrequently employed as an isolated procedure. However many Authors reported their experience on this treatment, in case of critical limb ischemia in patients without significative lesions of the aortofemoral district. Our late four year experience concerns of 22 patients (18 male, 3 female). All the patients had severe ischemia of the lower limbs, with serious symptoms, such as invalidating claudicatio (13), rest pain (7) and gangrene (2). Twenty-two profundaplasty were performed as the only reconstructive procedure. There was no postoperative mortality. Two patients had above knee amputations (15 days and 14 months after the revascularization). All of the other patients improved and follow-up extended to 48 months shows a limb salvage rate of 90%. In conclusion, on the basis of our experience, we think that the operation is recommended, whenever possible, in patients with critical ischemia when the possibilities of more extensive revascularization procedures are considered to be poor. PMID- 1291923 TI - Ten years of surgery of aortic dissections and aneurysms. Clinical experience and original contributions. AB - From January '82 to April '91, 117 patients with aortic disease were operated upon at our University Hospital in Genoa, Italy. Thirty-seven had arch dissections or aneurysms; 66 had acute aortic dissection type A and 14 had aortic dissections or aneurysms type B, acute and chronic. Patients with arch or type B aortic pathology but without surgical indication and cases of post-traumatic aortic transections are not included. There were 84 male and 33 female patients with a mean age of 52 (6 min and 74 max). In the acute patients, the mean interval between clinical onset and surgery was 34 hours (6 min-72 max). All patients with primary arch disease had surgical repair with the aid of deep hypothermia and circulatory arrest (17-96 min). Type A dissections were treated with standard CPBP at 28 degrees C. Surgical techniques included direct suture of intimal tear alone, direct suturing of the two aortic stumps; interposition of Dacron tubular prosthesis; Bentall repair; separated valve and aortic replacement; an original aortic bulb aortoplasty with valve repair; arch replacement with resuturing of one or more aortic trunks. Human fibrin glue (Tissucol) was employed either as haemostatic agent, widely spread over the suture lines or as tissue adhesion agent between dissected aortic layers. Human fibrin glue is adopted because it gathers high glueing capacity and maintenance of the elastic property of the vessel wall. Hospital mortality (30 days) has been 25% in ascending aortic dissections (16/66 patients) and 50% in patients with arch disease (18/37 patients) who needed circulatory arrest. Late mortality 5/83 (6%). Reoperations for aortic valve insufficiency or re-dissection have been 7 (8.4%). Early diagnosis (increasing reliability of 2D-Echo and CT scans), aggressive surgery, meticulous myocardial and cerebral protection and introduction in clinical use of biological glues seem to be the milestones of present and further improvements in surgical results. PMID- 1291924 TI - [Electrocardiogram ambulatory monitoring: technological evolution and current prospectives]. AB - The value of ambulatory ECG monitoring in the investigation of arrhythmic or ischemic events with paroxysmal patterns is well-known and its use is widespread. More recently, technical advances in informatics and in ECG signal digitizing have rapidly developed the current available ambulatory ECG instruments, reducing the time necessary for pattern analysis meanwhile assuring acceptable accuracy and reliability of the results. ECG recording techniques other than traditional Holter monitoring are now available such as transtelephonic transmission of ECG signal recorded in real time or previously stored in solid state memory by intermittent recorders that can be switched on by the patients himself at the first prodroms or at the end of the event. These "loop recorders" make it possible to indefinitely extend ECG monitoring time, reducing costs and increasing record sensitivity in comparison to conventional Holter monitoring. Moreover, recent technological development of Holter monitoring makes it possible to perform heart rate variability analysis and late potentials research in addition to traditional analysis of cardiac rate and ventricular repolarization. Thus Holter recording may become, combined with other usual risk factors, a polyparametrical non invasive approach to sudden cardiac death risk assessment characterised by low cost/benefit ratio and by large screening capacity. PMID- 1291925 TI - [Coenzyme Q10: contractile dysfunction of the myocardial cell and metabolic therapy]. AB - Coenzyme Q10, a mitoquinone involved in mitochondrial energy synthesis and the removal of free radicals, may be lacking in a number of cardiac pathologies leading to reduced contractile activity. The administration of exogenous coenzyme Q10 may help to improve contractile activity. In order to assess this hypothesis 63 patients suffering from altered myocardial contractile function (29 dilated cardiopathies, 15 valvular cardiopathies, 19 ischemic cardiopathies) which presented a NYHA class above 2 were selected. The study was open and patients were subdivided into two groups, one of which received conventional therapy alone whereas the other also received exogenous coenzyme Q10. After 4 months of follow up clinical (NYHA class, effort tolerance) and echocardiographical (ventricular diameter and contraction fraction %) parameters were evaluated. In those patients treated with coenzyme Q10 and suffering from dilated cardiomyopathy a significant reduction in the NYHA class and a marked improvement in echocardiographic parameters were observed at the end of this period. The variations observed in other groups of patients treated were less conspicuous and not always statistically significant. The results of this study confirm that the association of coenzyme Q10 and conventional therapy may lad to a marked improvement in contractile function and correlated clinical conditions. PMID- 1291926 TI - [Clinical study of the therapeutic efficacy and tolerance of nimesulide in comparison with a sodium diclofenac in the treatment of acute superficial thrombophlebitis]. AB - The efficacy and tolerability of nimesulide were assessed in a randomized study versus diclofenac sodium in the treatment of 50 patients affected with acute superficial thrombophlebitis. Both drugs, administered in a dose of 1 tablet b.i.d. for 10 days, evidenced a prompt and effective analgesic and anti inflammatory activity. Particularly, the tolerability of nimesulide was excellent. PMID- 1291927 TI - [Usefulness of temporal bicameral stimulation in the interruption of refractory ventricular tachycardia]. AB - The occurrence of sustained ventricular tachycardia with worsening hemodynamic performance in patients with ischemic heart disease can represent a critical event when the arrhythmia, refractory to antiarrhythmic drugs, recurs after D.C. shock. In this case temporary DDD pacing can be a reliable alternative treatment. PMID- 1291928 TI - Managing: a major challenge. PMID- 1291929 TI - [Health promotion and health policy. The range of directions towards 2002]. PMID- 1291930 TI - The registration certificate--an obligation. PMID- 1291931 TI - [A stimulating learning milieu]. PMID- 1291932 TI - [Case management. The nursing business of care or cost]. AB - Less money spent on health services, cost-effectiveness, better productivity and more efficiency are some of the driving forces of contemporary "neo-liberalism" and political trends. How can nursing services and the profession's human values adapt in this difficult context? The authors describe the newest modality of patient care delivery system: nursing case management. They examine the factors and assumptions that led up to its development and point out the validity of asking some serious questions before embarking on the euphoria of case management. PMID- 1291933 TI - Practice checkup: it's your turn. PMID- 1291934 TI - Clinical prosthodontic management of a new implant system. AB - Just prior to the advent of the branemark implant, the Harvard consensus on implantology condemned all maxillary implants. While implant utilization has skyrocketed in the last few years integration of implants in the maxilla is a persistent problem and even the branemark implant enjoys a lower success rate in this bone. These observations underscore the higher failure rate of the maxillary implant and suggest the need for development of a new implant design configuration that would favour long term successful integration despite the attenuated maxillary attributes. Such is the intent of the ostial implant. The basic considerations concerning this device, its bioengineering, experimental performance and clinical trials are discussed elsewhere. The purpose of this paper is to describe clinical prosthodontic applications of this implant system. PMID- 1291936 TI - Should dental implants be an insured benefit? PMID- 1291935 TI - Tactile sensibility of sapphire endosseous dental implants. AB - Experiments are described in which the tactile thresholds of sapphire (bioceram) endosseous implants were measured and compared with those of natural teeth. The effects of local anaesthesia were determined in an attempt to localize the mechanoreceptors involved. The thresholds of the implants were higher than those of natural teeth but lower than those of another type of implant (alumina tubingen) examined in another study. The results of local anaesthesia testing indicated that the sensory receptors involved were located in the connective tissues around the implant. PMID- 1291938 TI - GST and commercial leasing. The impact on the dental profession. PMID- 1291937 TI - Combined use of bone graft and Biotes fixtures in the treatment of the severely resorbed upper jaws. AB - Horse-shoe shaped bone grafts from the hip together with biotes self-tapping fixtures were used to rehabilitate patients with extremely resorbed upper jaws. Our experience and results from the 10 first consecutive case have been analyzed to form the base for further use of the method. We have lost eight fixtures out of 57 so far. Surgical complications with exposure of the bone transplant have occurred in three patients. A surprisingly good recovery from the hip has been seen in all of the patients. Certain technical precautions such as construction of a splint in the dentulous or partially dentulous jaw to prevent occlusal trauma towards the transplant have been made to avoid complications such as rupture of the mucosal flap. The method should be used with great care and the case meticulously chosen to avoid individuals who do not have the right motivation for the long-lasting and demanding surgical and prosthetic procedures. The combined use of implants and transplants should not be used routinely until a long-term evaluation of the method has been made to minimize potential drawbacks. PMID- 1291939 TI - The management of soft tissue defects using the "gingival shaving" technique. AB - A simple, effective technique is described for the correction of unfavourable gingival contour during post-surgical or pre-prosthetic procedures. Termed the "gingival shaving technique", it is conducted with high-speed course diamond burs. Results are relatively rapid and predictable, especially in cases where esthetics are most desirable. The technique can be performed by the periodontist or prosthodontist, and can be repeated until satisfactory gingival contour is achieved. Case selection, careful preparation, and post treatment management and care are essential for success. PMID- 1291940 TI - Operative arthroscopy of the temporomandibular joint. PMID- 1291942 TI - Some facts about oral cancer or how we can do it better. PMID- 1291941 TI - Ludwig's angina: a place for steroid therapy in its management? AB - Ludwig's angina is an uncommon but potentially fatal condition which presents as a hard swelling of the floor of the mouth. It spreads rapidly as a gangrenous process that may cause death through local airway obstruction. Ludwig's angina carried a 54% mortality rate in the preantibiotic era which has now been reduced to approximately 4%. Diagnosis is based on history and clinical observation. Currently described treatment involves protecting the airway and managing the infection with antibiotics and surgical drainage when indicated. PMID- 1291944 TI - An art career in dentistry. PMID- 1291943 TI - The risk of transmission of human immunodeficiency virus in dental practice. AB - After a decade of study of the acquired immunodeficiency syndrome (AIDS) there is evidence to address the concerns of dental staff about possible transmission of human immunodeficiency virus (HIV). This paper reviews that evidence which demonstrates an extremely low risk of transmission of HIV to staff and patients. Only a few isolated cases have implicated transmission during dental practice, however, there are no proven cases where seroconversion has been demonstrated in relation to an exposure during dental treatment. PMID- 1291945 TI - Disposal of biomedical waste--a guide for the sole practitioner. PMID- 1291946 TI - To rinse or not to rinse (better not get rid of that cuspidor) PMID- 1291948 TI - The diagnostic process. PMID- 1291947 TI - Immediate placement of osseointegrated dental implants into extraction sockets: advantages and case reports. AB - Osseointegrated dental implants have proven to be predictably successful when appropriate guidelines are followed. The technique as outlined by branemark includes a post-extraction period of up to 12 months in order to allow for bone healing. This delay, combined with ridge resorption following extraction, may contribute to several problems. Insufficient available bone for ideal implant placement and prolonged treatment time are two common difficulties. Recently, several investigators have reported immediate placement of dental implants into extraction sockets achieving excellent results while, at the same time, minimizing or eliminating the above-mentioned difficulties. This paper will discuss the technique of immediate placement of osseointegrated dental implants into extraction sockets and its potential advantages. A future article will detail surgically-related difficulties with this technique. PMID- 1291949 TI - Modern concepts in endodontics. Part 1. Diagnosis. AB - Diagnosis is the basic procedure from which further endodontic treatment decisions flow. Although we still use diagnostic tools which differ little from those of 50 years ago, our understanding and interpretation of their results has been slowly changing. As an example, we now believe that the painful responses to hot and cold occur via different a delta and C fibre pathways, involving changes in intra pulpal pressure and neuropeptides such as VIP and SP. As treatment planning is becoming more sophisticated and treatment modalities and options are expanding, correct endodontic diagnosis is even more important in the new age of rising patient expectations and ever-increasing legal complexities. Endodontists are frequently called upon to deal with difficult diagnostic situations, or manage situations of misdiagnosis where treatment has been initiated but the original chief complaint mysteriously persists. In the future, new exciting techniques such as pulse oximetry or laser doppler analysis may be clinically available as endodontic diagnostic aids. This paper will try and cover some of the broader concepts involved in correctly diagnosing a patient's chief complaint. PMID- 1291950 TI - How not to sell your practice. PMID- 1291951 TI - [The significance of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the pathogenesis of generalized forms of meningococcal infection in children]. PMID- 1291952 TI - [Influenza B in the winter-spring season of 1991 in children (based on polyclinic and hospital data)]. PMID- 1291953 TI - [The clinico-laboratory characteristics of paralytic poliomyelitis with the regular immunization of children with the Sabin live vaccine]. PMID- 1291954 TI - [The efficacy of the ADTP-vaccine immunization of children with different courses of the vaccinal period]. PMID- 1291955 TI - [The reasons for unfavorable outcomes in suppurative meningitis in children in the coal-mining region of Russia and the prospects for improving the treatment results]. PMID- 1291956 TI - [The treatment of intrahepatic cholestasis in newborns and infants in the first months of life living in the southern Kuznetsk Basin]. PMID- 1291957 TI - [New approaches to the treatment of confirmed and suspected community-acquired pneumococcal pneumonia]. PMID- 1291958 TI - [The clinical polymorphism and diagnostic and treatment characteristics of the convulsive syndrome in newborn infants]. PMID- 1291959 TI - [The effect of the endovascular laser irradiation of the blood on the indices of cyclic nucleotide metabolism in nursing infants with severe forms of pneumonia]. PMID- 1291960 TI - [Histiocytic syndromes in children: the classification problems and diagnostic criteria]. PMID- 1291961 TI - [The pathogenesis of diabetic fetopathy]. PMID- 1291962 TI - [The work experience of the department for infants of a pediatric polyclinic]. PMID- 1291963 TI - [A case of an apparent life-threatening event in an infant in the first year of life]. PMID- 1291964 TI - [The clinical manifestations of congenital rubella]. PMID- 1291965 TI - [A case of intestinal septicopyemia caused by Yersinia enterocolitica in a 13 year-old girl]. PMID- 1291966 TI - [The efficacy of kalmagin in chronic nonspecific diseases of the digestive organs]. PMID- 1291967 TI - [The centenary of the Moscow Society of Pediatric Physicians]. PMID- 1291968 TI - [Immunity in iron deficiency]. PMID- 1291969 TI - [Uric acid and arterial hypertension]. PMID- 1291971 TI - Mandibular repositioning to enhance athletic performance: is it well founded? And more importantly, is it safe? PMID- 1291970 TI - Guidelines for diagnosis and management of disorders involving the temporomandibular joint and related musculoskeletal structures. American Society of Temporomandibular Joint Surgeons. PMID- 1291972 TI - Conservative and successful treatment of temporomandibular dysfunction in a private rural practice. PMID- 1291973 TI - Avoiding abandonment. PMID- 1291974 TI - Computer takeover? PMID- 1291975 TI - Proof of the project. PMID- 1291976 TI - Family festivities. PMID- 1291977 TI - Home help. PMID- 1291978 TI - Safe as houses. PMID- 1291979 TI - Perceptions of deafness. PMID- 1291980 TI - Special delivery. Interview by Daloni Carlisle. PMID- 1291981 TI - Play school. PMID- 1291982 TI - Breaking the news. PMID- 1291983 TI - AIDS in Spain. PMID- 1291984 TI - Listening in. PMID- 1291986 TI - The changing role of the nurse teacher. PMID- 1291987 TI - Clients still prefer traditional GUM clinics. PMID- 1291985 TI - Encouraging fathers to care for babies. PMID- 1291988 TI - Learning disabilities. Sexual awareness. PMID- 1291989 TI - Learning disabilities. Skilled transfer. PMID- 1291990 TI - Learning disabilities. Adapt and survive. PMID- 1291991 TI - Mandatory teaching to boost AIDS awareness demanded. PMID- 1291992 TI - Co-prescribing with NSAIDs. PMID- 1291993 TI - Shortness of breath. PMID- 1291994 TI - Clinics for healthy children. PMID- 1291995 TI - Screening for oral cancer. PMID- 1291996 TI - Arthroscopy of the hip joint. PMID- 1291997 TI - Heartsink patients--optimising care. PMID- 1291998 TI - Coping strategies for GPs. PMID- 1291999 TI - Passing the MRCGP. Strategies for preparation. PMID- 1292000 TI - Travellers' diarrhoea. PMID- 1292001 TI - Viral hepatitis. PMID- 1292002 TI - Irritable bowel syndrome. PMID- 1292003 TI - Early diagnosis of gastrointestinal cancer. PMID- 1292004 TI - Treatment of epilepsy. PMID- 1292005 TI - 'Health policing' erodes civil liberties. PMID- 1292006 TI - Preventive medicine is good for your health. PMID- 1292007 TI - Functional properties of cloned melanogenic proteins. AB - Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct catalytic activities--tyrosine hydroxylase, 3,4 dihydroxyphenylalanine (DOPA) oxidase and DHI (5,6-dihydroxyindole) oxidase. The brown locus encodes TRP-1 (tyrosinase-related protein-1), which has the same, but greatly reduced, catalytic potential. The slaty locus encodes TRP-2, another tyrosinase related-protein, which has DOPAchrome tautomerase activity. In this study we have examined the enzymatic interactions of these proteins, and their regulation by a novel melanogenic inhibitor. We observed that tyrosinase activity is more stable in the presence of TRP-1 and/or TRP-2, but that the catalytic function of TRP-2 is not affected by the presence of TRP-1 or tyrosinase. Other factors also may influence melanogenesis and a unique melanogenic inhibitor suppresses tyrosinase and DOPAchrome tautomerase activities, but does not affect the spontaneous rate of DOPAchrome decarboxylation to DHI. The results demonstrate the catalytic functions of these proteins and how they stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized by the melanocyte. PMID- 1292008 TI - Molecular characterization of the p(un) allele of the mouse pink-eyed dilution locus. AB - The mouse pink-eyed dilution locus, p, located on chromosome 7, mediates coat and eye color. The human correlate of this gene may underlie some forms of tyrosinase positive oculocutaneous albinism. Mutations at the p locus result in a reduction in pigmentation of the eyes and coat. Although most mutant p alleles (including all spontaneous mutations) affect only pigmentation, several mutant alleles (all radiation induced) are also associated with a variety of other phenotypes. We have focused our attention on the p(un) mutant allele, a spontaneous mutation, exhibiting one of the highest reversion frequencies reported for a mammalian mutation. Using a new technique, genome scanning, we have cloned fragments of genomic DNA from the p locus that are associated with a DNA duplication in p(un) DNA. These fragments can now be used to locate the p gene-encoding sequences and aid in the molecular characterization of complex mutant p alleles. PMID- 1292009 TI - Analysis of mutations in the copper B binding region associated with type I (tyrosinase-related) oculocutaneous albinism. AB - Mutations of the tyrosinase gene are responsible for type I (tyrosinase-related) oculocutaneous albinism (OCA), an autosomal recessive genetic syndrome with a broad phenotypic spectrum. Mutant tyrosinase alleles can be associated with no melanin synthesis (I-A, tyrosinase-negative OCA), small to moderate amounts of melanin (I-B, yellow OCA) or unusual pigment patterns (I-TS, temperature sensitive OCA). A total of 26 mutations of this gene have been described in type I OCA. Analysis of all known mis-sense mutations (n = 17) shows that most cluster in three areas of the coding region. Two clusters involve the copper A or copper B binding sites and may disrupt the metal ion-protein interaction necessary for enzyme function and the third cluster is located in exon I. Computer modeling of the secondary structure of the copper binding regions based on homology with the known crystal structure of hemocyanin show that they both consist of two alpha helices containing three histidine ligands that complex to a single copper atom. Mutations in the copper B binding region lie in the region between the two alpha helices that consists of a loop structure. These mutations may affect tyrosinase activity by either altering the position of the alpha helical domains and thus preventing proper copper binding to the histidine ligands, or affecting a catalytic or substrate binding site located between the two alpha helical domains. PMID- 1292010 TI - Mutations of the tyrosinase gene in oculocutaneous albinism. AB - Since our first report showing that the phenotype of tyrosinase-negative or type IA oculocutaneous albinism (OCA) is a consequence of a mutation in the tyrosinase gene (Tomita et al., Biochem. Biophys. Res. Commun., 164:990-996, 1989), a number of mutations were found in the tyrosinase gene of OCA patients. However, to establish the molecular basis of OCA in each patient, we must carry out several important experiments as summarized here. First, we should confirm that the cloned or amplified genomic DNA segments are not derived from the pseudogene or related gene. It should be noted that the putative tyrosinase pseudogene contains the sequence almost identical to exons 4 and 5, including their exon/intron boundaries of the authentic tyrosinase gene. Thus, the mutations, detected in exon 4 or 5 amplified from genomic DNA, must be carefully analyzed to exclude a possibility that the mutation is located in the pseudogene. Second, it is of significance to confirm the promoter activity of the patients' tyrosinase gene. Accordingly, we established the cell-free transcription system derived from melanoma cells where the cloned tyrosinase gene is faithfully transcribed. Finally, transient expression assay of mutant tyrosinase is invaluable to conclude that OCA phenotypes are associated with the mutant tyrosinase alleles. I also discuss the implications of a cluster of mutation sites in exon 1 coding for the amino-terminus of tyrosinase. PMID- 1292011 TI - Phylogeny of regulatory regions of vertebrate tyrosinase genes. AB - Highly homologous DNA elements were found to be shared by the upstream regions of the mouse tyrosinase and tyrosinase related protein (TRP-1) genes. Several nuclear proteins were shown to bind to both of these upstream regions. Shared homologous DNA elements were also found in the 5' flanking sequences of Japanese quail and snapping turtle tyrosinase genes. Shared homologous nucleotide sequences were found to be scattered like an archipelago in the 5' upstream regions of mouse and human tyrosinase genes. Comparisons between Japanese quail and snapping turtle tyrosinase genes gave similar results. On the contrary, mammalian (mouse and human) and nonmammalian (quail and snapping turtle) tyrosinase genes did not show significant homology in their 5' upstream regions. In contrast, coding sequences in the first exons of vertebrate tyrosinase genes and their deduced amino acid sequences were found to be highly conserved except for their putative leader sequence-coding regions. PMID- 1292013 TI - Expression of tyrosinase gene in transgenic albino mice: the heritable patterned coat colors. AB - To elucidate the regulatory mechanism for tyrosinase gene expression in vivo, we microinjected a mouse tyrosinase minigene, mg-Tyrs-J, into the fertilized eggs of BALB/c albino mice. As a result, we obtained six pigmented founder mice that exhibited non-standard coat color variations as well as the wild-type phenotype. These founder mice were subsequently crossed with BALB/c albino mice to establish the transgenic lines. As a consequence, two primary lines and five sublines have been obtained from four of the six founder mice. We found that not only uniformly pigmented phenotypes but also patterned phenotypes were inherited by their descendants. The possible underlying mechanism of the patterned phenotypes is discussed. PMID- 1292012 TI - Molecular characterization of the mouse tyrosinase gene: pigment cell-specific expression in transgenic mice. AB - Tyrosinase is the key enzyme in melanin synthesis, and is expressed in the pigment epithelium of the retina, a cell layer derived from the optic cup; and in neural crest-derived melanocytes of skin, hair follicle, choroid, and iris. The tyrosinase gene has been cloned and shown to map to the well-characterized c locus (albino locus) of the mouse. Subsequent studies demonstrated that a functional tyrosinase minigene was able to rescue the albino phenotype in transgenic mice. The transgene was expressed in a cell type-specific manner in skin and eye. During development of the mouse, the tyrosinase gene is expressed in the pigment epithelium of the retina as early as day 10.5 of gestation. In the hair follicle, tyrosinase gene expression is detected from day 16.5 onwards. This cell-type-specific expression is largely reproduced in transgenic mice. Our results suggest that sequences in the immediate vicinity of the mouse tyrosinase gene are sufficient to provide cell type-specificity and developmental regulation in melanocytes and the pigment epithelium. PMID- 1292014 TI - The expression of mouse tyrosinase in chick cells in vitro and in vivo when controlled by a constitutive promoter. AB - Virally introduced mouse tyrosinase expression was checked both in vitro and in vivo in chicken cells and tissues. The results indicate that a constitutive promoter is able to express mouse tyrosinase in a variety of cells and tissues both in vitro and in vivo. Tyrosinase expression is marked by pigment production in situ, which is visible at macroscopic as well as microscopic levels without the use of substrates. It is concluded that tyrosinase can be a valuable marker for tracking gene insertion since it is spontaneously expressed. The expression of tyrosinase in some cells and tissues has a detrimental effect, however, and should be controlled by tissue-specific promoters. PMID- 1292016 TI - Tyrosinase and the regulation of coat color changes in C3H-HeAvy mice. AB - Hair follicular tyrosinase activity was measured during hair growth in neonatal, pubertal, and adult C3H-HeAvy mice that show differences in coat color as a result of changes in the synthesis of eumelanin and pheomelanin. Tyrosinase activity increased during hair growth in all mice but higher levels were found at puberty, when the mice grow a dark, eumelanin coat of hair, than during early and adult life, when the hair follicular melanocytes produce mainly pheomelanin. This suggests that tyrosinase is more important for the synthesis of eumelanin than that of pheomelanin. The increased tyrosinase activity associated with eumelanogenesis in the pubertal mice could not be explained by enhanced transcription of the tyrosinase gene or enzyme synthesis and appeared to be the result of a post-translational activation. Such an activation of tyrosinase was lacking in the neonatal and adult mice; in the latter this was accompanied by a reduction in the glycosylation of tyrosinase and the proportion of enzyme associated with the melanosomal fraction. Our findings suggest that post translational mechanisms are important control points in the regulation of tyrosinase and that differences in their level of activation are responsible for determining the patterns of melanogenesis in the C3H-HeAvy mice, but it is still not clear how these mechanisms are regulated. Although cyclic AMP increased tyrosinase synthesis it had no post-translation activating effect. The neonatal mice, unlike their pubertal and adult counterparts, also lacked dopachrome converting activity and TRP tyrosinase-related protein-1 expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292015 TI - Expression and transmission of wild-type pigmentation in the skin of transgenic orange-colored variants of medaka (Oryzias latipes) bearing the gene for mouse tyrosinase. AB - Transgenic fish carrying a reconstructed mouse tyrosinase gene, mg-Tyrs-J, were produced by microinjecting the gene into the oocyte nucleus of an orange-colored variant of medaka (Oryzias latipes). Of 64 oocytes microinjected and subsequently inseminated, 13 embryos developed normally beyond hatching and three of them exhibited brown skin pigmentation in the adult as was commonly observed in the wild type of this species. Light and electron microscopic examination disclosed a ubiquitous distribution of typical melanophores in the skin of these transgenic fish. Judging from their population density and distribution pattern, it was presumed that melanogenesis in these fish was elicited in amelanotic melanophores that resided in the skin of the orange-colored fish of this variant. Immunofluorescence with use of the anti-mouse tyrosinase antiserum lacking reactivity to medaka tyrosinase clearly disclosed that the gene introduced was expressed in the melanophores of transgenic fish. Crosses of female transgenic fish and males from an orange-colored variant yielded offspring exhibiting wild type or orange-colored pigmentation in a ratio of 1:1, thus implying that mg-Tyrs J integrated into the medaka genome behaves like a dominant gene. Little melanogenesis was observed in xanthophores, leucophores and iridophores in transgenic fish, suggesting possible specificity in recognition of teleostean cell types (i.e., melanophores) by the regulatory region of the mouse tyrosinase gene. PMID- 1292017 TI - The molecular basis of human piebaldism. PMID- 1292018 TI - Proliferation and neoplastic transformation of pigment cells in metallothionein/ret transgenic mice. AB - Although melanoma is a common human disease, there were few animal models in which melanoma developed at high incidence. To date, the Xiphophorus fish has been used as a model system to study melanoma formation. Studies on this fish showed the presence of a dominant oncogene, Tu, which encodes a transmembrane, tyrosine kinase of epidermal growth factor receptor type (Wittbrodt et al., Nature, 341:415-421, 1989). Recently, we succeeded in establishing novel transgenic mouse lines in which melanosis and melanocytic tumors developed stepwise by introducing another transmembrane tyrosine kinase oncogene, ret (Iwamoto et al., EMBO J., 10:3167-3175, 1991). In our transgenic mice, high levels of expression of the ret transgene induced proliferation and neoplastic transformation of melanin-producing cells. In addition, crossbreeding experiments between transgenic mice and Wv mice showed that the ret oncogene can also induce melanogenesis and melanocyte development in Wv/Wv mice. PMID- 1292019 TI - Molecular cascades in UV-induced melanogenesis: a central role for melanotropins? AB - When human skin is exposed to ultraviolet (UV) light, a highly complex cascade of events ensues that culminates, among other things, in increased skin melanin content. From analyses at the tissue and cellular level, it has been shown that following exposure to UV light there is an increase in the number of active melanocytes in the basal layer of the epidermis, and individual melanocytes are stimulated to produce more melanin. In addition, the rate of transfer of melanosomes from melanocytes to keratinocytes is apparently increased, although the role of UV light in this process remains to be demonstrated. Recent biochemical evidence is reviewed on factors that regulate these processes. A plausible explanation for the effects of UV on pigmentation is that there are mechanisms in the skin for the orderly, regulated reception of UV signals that are then transduced to initiate the cascade. The signals involve both melanocytes and keratinocytes, and available evidence supports a model in which melanotropins and their receptors play a central role in the process. PMID- 1292021 TI - The pigmentary system and inflammation. PMID- 1292020 TI - Melanocyte-stimulating properties of arachidonic acid metabolites: possible role in postinflammatory pigmentation. AB - Normal human epidermal melanocytes became swollen and more dendritic with an increase in the amount of tyrosinase and immunoreactive b-locus protein when they were cultured for 2 days with the following arachidonic acid metabolites: prostaglandin (PG) D2, leukotriene (LT) B4, LTC4, LTD4, LTE4, thromboxane (TX) B2 and 12-hydroxy eicosatetraenoic acid (12-HETE). The effect of LTC4 was particularly strong compared to that of PGE2, about which we have previously reported. On the other hand, PGE1, PGF2 alpha and 6-ketoPGF1 alpha did not show any significant stimulatory effect. These data suggest that arachidonate-derived chemical mediators, especially LTC4, may be responsible for the induction of post inflammatory hyperpigmentation of the skin. PMID- 1292022 TI - Canada's first hospital dental clinic for patients with HIV infection. PMID- 1292023 TI - A hospital-based dental clinic for patients with HIV infection in the United States. PMID- 1292025 TI - An evaluation of dental hygiene practice standards workshops. PMID- 1292024 TI - Recent recommendations for hepatitis B vaccination. PMID- 1292026 TI - Behavioural techniques in oral health promotion. PMID- 1292027 TI - Oral health in old age--practical problems and practical solutions. PMID- 1292028 TI - Effects of drug therapy on oral health of older adults. PMID- 1292029 TI - Dental implantology and the older adult. Implications for oral hygiene maintenance. PMID- 1292031 TI - Merry Christmas John. PMID- 1292030 TI - Nutrition concerns of and for senior canadians. PMID- 1292032 TI - Complications of suction-assisted lipoplasty. AB - The potentially fatal, surgical, and aesthetic complications of suction-assisted lipoplasty are discussed in this article. Prevention through early detection and risk management will be emphasized. PMID- 1292033 TI - Writing for publication: advice to potential authors. AB - If you have thought about writing for publication, then take the time to read this article! Plastic Surgical Nursing Editor Joyce Black, MSN, RNC, CPSN, will discuss each step of the process, including tips on generating a topic, writing the first draft, editing your work, and submitting to a journal. Advice to authors on submitting to Plastic Surgical Nursing will also be discussed. PMID- 1292034 TI - The nurse as patient advocate. PMID- 1292035 TI - Safety measures are important in the operating room. Association of Operating Room Nurses, Inc. PMID- 1292036 TI - Sexual harassment in the workplace. PMID- 1292037 TI - Patients with high exposure to silicone need not be concerned by report. PMID- 1292038 TI - Ventricular size and regional cerebral blood flow in schizophrenia: an attempted replication. AB - We attempted to replicate the finding of Berman et al. (1987) that frontal cortical blood flow correlated inversely with ventricular size in schizophrenia. Computed tomography and high-resolution 99m-Tc-HMPAO single photon emission computed tomography were performed in 25 right-handed chronic schizophrenic men engaged in a word-fluency task. Weak, nonstatistically significant inverse correlations were found between the ventricle-brain ratio (VBR) and frontal cortical blood flow. The VBR was significantly inversely correlated with the ratio of left to right medial frontal blood flow. PMID- 1292039 TI - Uptake and utilization of [beta-11C]5-hydroxytryptophan in human brain studied by positron emission tomography. AB - The immediate precursor in the serotonin synthetic route, 5-hydroxytryptophan (5 HTP), labeled with 11C in the beta position, has become available for studies using positron emission tomography (PET) to examine serotonin formation in human brain. Normalized uptake and intracerebral utilization of tracer amounts of [beta 11C]5-HTP were studied twice in six healthy male volunteers, three of them before and after pharmacological pretreatments. The kinetic model defines regional utilization as the relative regional radioactivity accumulation rate. Repeat studies showed good reproducibility. Pretreatments with benserazide, p chlorophenylalanine (PCPA), and unlabeled 5-HTP all significantly increased uptake of [beta-11C]5-HTP. The utilization rates in both striatal and frontal cortex were higher than those in the surrounding brain, indicating that PET studies using [beta-11C]5-HTP as a ligand quantitate selective processes in the utilization of 5-HTP. We tentatively interpret uptake and utilization as a measure of brain serotonin turnover, the selectivity of which was shown by pharmacological interventions in vivo. PMID- 1292040 TI - SPECT imaging of serotonin2 receptors in depression. AB - Changes of serotonin2 (5HT2) receptors have been described in depression, and long-term antidepressant treatment has been shown to decrease the number of 5HT2 receptors. In this study, single photon emission computed tomography (SPECT), with 2-123I-ketanserin as a ligand, was used to investigate 5HT2 receptors in vivo in the brain of depressed patients and normal volunteers. A higher uptake of the tracer was observed in the parietal cortex of the patients, and there was a right greater than left asymmetry in the infero-frontal region of the depressed subjects and not in that of the control subjects. These findings could indicate changes in 5HT2 receptors in major depression. PMID- 1292041 TI - Left temporal hypoperfusion in catatonic syndromes: a SPECT study. PMID- 1292042 TI - An interview with Ernest Wolf. Part II: The analytic years to 1990. Interview by Virginia Hunter. PMID- 1292043 TI - On dreaming of one's patient: dense objects and intrapsychic isomorphism. PMID- 1292044 TI - A case of rape: real and imagined. PMID- 1292045 TI - A psychoanalytic interpretation of Ovid's myth of Narcissus and Echo. PMID- 1292046 TI - Inclined toward the marvelous: romantic uses of clinical phenomena in the work of Frederic W.H. Myers. PMID- 1292047 TI - The suicide of a survivor: some intimate perceptions of Bettelheim's suicide. PMID- 1292048 TI - Sex, lies and videotape: Hopper country. PMID- 1292049 TI - Case #10. Taurodont. PMID- 1292050 TI - A cookbook approach isn't answer to all perio disease assessments. PMID- 1292052 TI - The road to autonomy. PMID- 1292051 TI - Treatment for anxiety ranges from therapy to medications. PMID- 1292053 TI - Eye to eye. PMID- 1292054 TI - Mouthguards are an athlete's best friend. PMID- 1292055 TI - Civilian service in military offers opportunity for growth. PMID- 1292056 TI - Spore testing of sterilizers ensures patients' protection. PMID- 1292058 TI - Answers to questions about self-regulation. PMID- 1292057 TI - Returning to the fold. PMID- 1292059 TI - Do your part to further the profession: recruit. PMID- 1292060 TI - We have the power to change, but will we take the risk? PMID- 1292061 TI - Research conducted in the office sometimes more relevant to practice. PMID- 1292062 TI - On-the-job hazards. PMID- 1292063 TI - Case study #9 . Tooth resorption. PMID- 1292064 TI - Hazardous waste must be clearly labeled, stored before disposal. PMID- 1292066 TI - It's your right ... or is it? PMID- 1292065 TI - Don't spend another sleepless night counting herds of sheep. PMID- 1292067 TI - Consensus sequences at transcription start sites. AB - A new consensus sequence (A/G)CTGTTC is defined for the cap regions of a number of eukaryotic structural genes. This sequence is related to other elements involved in transcription initiation, including the CAAT and -35 motifs. PMID- 1292068 TI - Diagnostic aspects, functional significance and therapy of simple renal cysts. A clinical, radiologic and experimental study. AB - Simple renal cysts and renal cell carcinomas constitute the majority of the renal masses disclosed by radiologic methods. The reliability of radiologic diagnosis was studied in patients with different renal mass lesions. Based on the experiences from the study, ultrasonography is recommended when a renal mass is discovered at urography. Computerized tomography and rarely angiography and percutaneous puncture for cytologic examination are necessary when all criteria of a simple renal cyst have not been fulfilled. Forty-one patients with renal cell carcinoma and additional renal masses in the same or contralateral kidney were studied. In 3 patients the radiologic methods were insufficient to establish a definite diagnosis of the additional renal mass occurring in the kidney contra lateral to the renal cell carcinoma. Only explorative surgery established the true diagnosis. A method for estimating single kidney glomerular filtration rate by gamma camera renography using 99mTc-DTPA was studied. The accuracy and reproducibility was satisfactory when compared to the 51Cr-EDTA clearance reference method. The functional consequences of simple renal cysts and percutaneous puncture were studied by gamma camera renography before as well as after puncture and evacuation of the cysts. Signs of obstruction of the renal outflow were rarely seen. No other effect on renal function was found and percutaneous puncture with evacuation of the cysts did not improve renal function significantly. The therapeutic efficacy of percutaneous puncture and instillation of bismuth-phosphate was compared to percutaneous puncture alone and to the natural course of simple renal cysts. After 24 months there were no significant difference in size between cysts that were only punctured and those that had no intervention. The cysts that were treated with bismuth-phosphate disappeared or diminished with few exceptions. The effects of bismuth-phosphate on the renal parenchyma and renal outflow tract were investigated by microangiography and histopathology in an experimental study. A zone of connective tissue around the deposited bismuth-phosphate was seen and no effects on glomeruli or renal vessels were disclosed. It is concluded that the radiologic diagnosis of simple renal cysts is definite when all diagnostic criteria are fulfilled by ultrasonography or computerized tomography. Simple renal cysts have no effect on renal function. Therapeutic interventions because of simple renal cysts are not indicated in patients without outflow obstruction. PMID- 1292069 TI - Carcinoma-in-situ of the testis: screening and management. PMID- 1292070 TI - Recurrence of urethral stricture and late results after optical urethrotomy: comparison of strictures caused by toxic latex catheters and other causes. AB - During the years 1977-1985, 183 new urethral strictures were diagnosed and treated by optical urethrotomy. A sharp increase in the incidence of iatrogenic strictures was found in 1980-1981 which normalized after simultaneous changing of the resectoscope, lubricant and catheter type. In fact, an "epidemic" of urethral strictures associated with the use of indwelling latex catheters in cardiac operations was observed in Finland in those years. It is suggested that toxic latex catheters exacerbated the local mechanical injury caused by endoscopic surgery. The recurrence rate for our "epidemic" strictures was 54%, whereas in other cases it was 37% (p = 0.02), but there were no differences in the later course. The patients age, stricture site, postoperative period of catheter drainage, length, diameter or multiplicity had no effect on the recurrence rate after the initial urethrotomy. Stricture recurrences occurred up to 8 years after the initial operation. Because of the chronic nature of the urethral stricture, a follow-up time of at least 10 years is needed before the final results of urethrotomy can be evaluated. PMID- 1292071 TI - Micturition habits of older people. Voiding frequency and urine volumes. AB - A questionnaire study was carried out among elderly subjects (mean age 73.6 +/- 6.1 years (SD)) with a response rate of 74% (n = 1,115). It covered various aspects of health, symptoms and disease. 26% (n = 287) stated that they had two or more micturitions per night. A subgroup consisting of healthy older people, 39 men and 56 women with an average age of 73.9 +/- 4.9 years and 70.8 +/- 5.3 years, respectively, was studied concerning the distribution of diuresis and the frequency of voiding. The combined 24-hour diuresis (average for three 24-hour periods) was 1,400-1,600 ml, with a quotient between day and night of about 1, except the group with only one micturition at night (12 hours), where it was 1.8. The micturition volume between 08-20 h was less than between 20-08 h. The micturition volumes during both periods were significantly less with an increase in the number of voidings between 20-08 h. The quotient between the micturition volume 08-20 h and 20-08 h was strikingly constant (about 0.7). The finding of equally large urine volumes both day and night differs from that among younger adults in whom the diuresis is twice as large in the day as in the night. PMID- 1292072 TI - Use of indomethacin in the prophylaxis of ureteral colic following extracorporeal shock wave lithotripsy. AB - Ureteral obstruction leading to pain seems to be related to an increase of renal prostaglandins (PG). We designed a prospective double-blind, placebo controlled protocol for evaluating the effect of indomethacin, a PG-synthetase inhibitor, in the prophylaxis of ureteral colic following extracorporeal shock wave lithotripsy (ESWL). Sixty patients undergoing ESWL were randomized into two groups, group 1 (study group) received 50 mg indomethacin capsule three times daily and group 2 (control group) received multiple-vitamin tablet three times daily. Twenty-four hours urine samples were collected before and three days after ESWL was performed for PGE2 (predominant renal PG) determination. Subjective pain after ESWL was recorded with pain score (0-10 degrees). Oral codein or pethidine injection were available for relieving pain following ESWL. The pain score, analgesic requirement and urinary PGE2 in pre- and post-ESWL were used to compare the two groups. The pain score was 4.00 +/- 0.25 and 3.00 +/- 0.25 in the control and study groups respectively; it had a statistically significant difference (p < 0.01). In control group, 12 and 14 patients required 23 doses of codein and 18 doses of pethidine. In the study group, three and four patients required five doses of codein and eight doses of pethidine. The difference was statistically significant (p < 0.05). In the control group, the mean pre- and post-ESWL urinary PGE2 was 305 +/- 65.8 and 474 +/- 101 micrograms/24-hr respectively. In the study group, the mean pre- and post-ESWL urinary PGE2 was 289 +/- 60.7 and 186 +/- 26.5 micrograms/24-hr respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292073 TI - Carcinoma of the renal pelvis. Experience of 80 cases. AB - The clinical course and association with other urothelial carcinomas was studied in 80 patients with carcinoma of the renal pelvis. At the time of diagnosis macroscopic haematuria was the most common symptom. Urography and retrograde pyelography gave the most accurate diagnoses. Sixty-eight patients (85%) had transitional cell carcinomas, 39 had a history of another urothelial carcinoma either before or after the diagnosis of the renal tumour, usually in the urinary bladder. A previous urothelial carcinoma together with a small renal tumour were predictive of the subsequent development of another urothelial tumour. Regular cystoscopy is recommended during follow-up because of the short observed interval between the development of carcinoma of the renal pelvis and a subsequent urothelial malignancy. The overall five-year survival was 20%. Survival did not depend on the operation, but was significantly related to the extent of locoregional or distant metastases at the time of diagnosis. Patients with such renal tumours that were preceded by or associated with other urothelial carcinomas had a more favourable median survival (42 months) than patients whose renal tumour was their first urothelial carcinoma (19 months). PMID- 1292074 TI - Skeletal metastases in 102 patients evaluated before surgery for renal cell carcinoma. AB - During a 3-year period a consecutive series of 102 patients were treated for renal cell carcinoma at one urological unit. Thirty-three patients (32.4%) had metastatic spread, but bone metastases were found in six patients only, i.e. 5.9% of the whole series and 18.2% of the patients with metastases preoperatively. The bone metastases had in all six patients given local symptoms first indicating radiography, and thereafter radionuclide scintigraphy of the entire skeleton. Bone scintigraphy performed merely by routine in 70 patients did not reveal one single case of bone metastasis. Only one patient had a solitary bone metastasis, and this metastasis was considered inoperable because of its location and size and the patient's age. The decision about nephrectomy was not in any case altered by the finding of bone metastases. Solitary bone metastasis must be diagnosed early since they may be radically removed. Routine scintigraphy of the skeleton in symptomless patients, however, has a low yield. Screening for skeletal metastases may therefore be best performed by careful physical examination and history-taking. PMID- 1292075 TI - Multiple renal masses in patients with renal cell carcinoma: diagnostic pitfalls and surgical implications. AB - Additional renal masses were found in the same or contralateral kidney in 41 of 131 patients with renal cell carcinoma. In 35 of the patients the additional renal masses were simple renal cysts situated in the kidney contralateral to the renal cell carcinoma in 16 patients, in the same kidney in 11 and bilaterally in 8 patients. Four patients had bilateral renal cell carcinomas. One patient had polycystic kidney disease as well as renal cell carcinoma and another patient had a benign tumour in the contralateral kidney. In 3 of the 30 patients with additional renal masses in the kidney contralateral to the renal cell carcinoma the radiologic examinations were insufficient to exclude malignancy. Only explorative surgery could establish a true diagnosis of these masses. PMID- 1292076 TI - Biochemical fingerprinting of urinary Escherichia coli causing recurrent infections in women with pyelonephritic renal scarring. AB - A biochemical fingerprinting system, especially designed for subtyping of Escherichia coli and suitable for screening large number of bacterial strains was used in a long-term follow-up study of 19 women with non-obstructive pyelonephritic renal scarring and recurrent urinary infections in order to examine whether recurrent infections mostly are relapses or reinfections in this group of patients. Seventy-six recurrent infections occurred during a 47-month follow-up (0.09 infections per observation month). The majority of the recurrences were reinfections (58/76, 76%) and 18 (24%) were relapses caused by E. coli. Approximately 50% of relapses and reinfections caused by E. coli were symptomatic while the majority of reinfections caused by other bacteria were asymptomatic (23/30, 77%). In one patient a relapse of E. coli infection occurred more than two years (745 days) after the initial infection. Reinfections may occur early (7 days) after cessation of antimicrobial therapy in this group of patients. Two patients had an episode of symptomatic bacteriuria 51 and 56 days after asymptomatic bacteriuria with the same E. coli strain was detected. Biochemical fingerprinting of the E. coli isolates revealed that they belong to a wide variety of biochemical phenotypes which indicates that they are not members of widespread uropathogenic clones. PMID- 1292077 TI - Urinary excretion of citrate, glycosaminoglycans, magnesium and zinc in relation to age and sex in normal subjects and in patients who form calcium stones. AB - One hundred and ninety-seven healthy subjects and 104 patients with idiopathic calcium stone disease had their urinary excretion of citrate, glycosaminoglycans, magnesium, and zinc measured and the results correlated with sex and age. In normal subjects the daily excretion of citrate, magnesium, and zinc increased with age to a maximum during the fifth decade and remained relatively constant until the eighth decade when they decreased. The daily excretion of magnesium and zinc were higher in men than in women, which was attributed to the higher body weights of the men. The urinary excretion of citrate, magnesium, and zinc related to creatinine remained relatively constant with age in adult life; analyses of magnesium and zinc excretion rates divided by urine creatinine did not distinguish men from women. There was no significant difference between men and women for citrate excretion in 24 hour urine, but the citrate:creatinine ratio was significantly higher in women than men. The higher citrate excretion in women may explain the lower incidence of calcium stones in women. The highest glycosaminoglycan excretion rates were seen during the first two decades which is why children and teenagers are less prone to develop calcium stones in spite of high urinary calcium concentrations. Urinary citrate and magnesium excretion were lower, and glycosaminoglycan and zinc excretion were higher, in stone formers than in controls. It seems that a decreased excretion of citrate and magnesium together with an increased excretion of calcium, may contribute to the formation of calcium stones. The role of urinary glycosaminoglycans and zinc in the formation of calcium stones remains uncertain. PMID- 1292078 TI - Decrease in renal function following decreased fibrinogen and raised fibrin degradation products in lupus nephritis with nephrotic syndrome. AB - To clarify the relationship between renal function and laboratory indicators of abnormal blood coagulation in lupus nephritis with nephrotic syndrome, we studied 28 patients with this disease over the 11 years. Follow-up tests included serial determination of plasma fibrinogen, serum fibrin degradation products (FDP), serum creatinine and endogenous creatinine clearance (Ccr) as well as other parameters. Either decreased fibrinogen, elevated FDP, or both were found in 13 cases. Taking as a criterion of decreased renal function an increase in serum creatinine above 0.2 mg/100 ml combined with a decrease in Ccr by more than 30% below the immediately preceding values, 11 of the above 13 patients showed a marked deterioration in renal function concurrently or within two weeks after the episodes of clotting disorder. Two other patients showed a less marked decrease in renal function. The 15 patients whose circulating fibrinogen and FDP remained normal did not show deterioration in renal function. The difference in renal function decrease between the groups with and without abnormal hemocoagulation indicators is significant. Our preliminary results indicate that when fibrinogen and FDP indicate intravascular hypercoagulation deterioration in renal function in patients with lupus nephritis is probable. PMID- 1292079 TI - Long term morbidity and mortality after kidney transplantation. AB - A cohort of 69 patients received a kidney transplant in the period 1963-1977. The mean observation time was 9.5 years. Accumulated follow-up time was 661.4 patients year. The mean (SE) 10-year survival was 55(5.9)%. Univariate analysis showed that female patients had poorer survival than male. Patients with a cadaveric donor had lower survival than those with a living donor. Also survival with different HLA-A,B match differed significantly. A multivariate analysis pinpointed nature of donor, cadaveric vs. living, as the sole independent predictor of mortality. Patients receiving a cadaveric kidney were on double (2.2) relative risk of mortality as compared to patients with a living donor. The major causes of death were infections during rejection treatment, and cardiovascular disease. Patients had low rates of morbidity. Our results showed satisfactory outcome of kidney transplantation. PMID- 1292080 TI - Renal transplantations from the same kidney donor: outcome of diabetic and non diabetic patients. AB - Diabetic (DM) nephropathy is an indication of renal transplantation in 30% of all cases in our hospital. We assessed retrospectively the outcome of these diabetics (DM) in comparison with their non-diabetic (NDM) controls. Each diabetic (n = 24) had a control (n = 24) receiving a kidney from the same donor. There was no difference in the stage of uraemia preoperatively. Anaesthesia and fluid therapy were standardized. Peroperative hypotension occurred more often in diabetics (NS). All operating parameters including cold ischaemia were comparable. Kidney function started immediately in 14/24 in the DM group and 13/24 in the NDM group and was delayed in 10/24 and 11/24, respectively. One diabetic patient rejected the transplant as did two non-diabetic patients. Postoperatively diuretics could be discontinued more often in the DM than in the NDM group (p < 0.05). Antihypertensives had to be started in the NDM more often (NS) than in the DM group. In conclusion, the outcome of diabetic patients after renal transplantation was comparable to their NDM controls. PMID- 1292081 TI - Effects of schistosomiasis on living kidney donors. AB - Twenty living kidney donors with schistosomiasis were compared with 20 uninfected donors for a mean follow-up period of 42 months (range 12-62). All patients with schistosomiasis had been treated preoperatively with antischistosomal chemotherapy. None of the donors developed any appreciable change in mean systolic or diastolic blood pressure during the follow-up period, though one infected and two uninfected donors had traces of protein in the urine. One uninfected donor developed microscopic haematuria. The two groups has similar reductions in renal function after unilateral nephrectomy. The response of the remaining kidneys to a combined infusion of dopamine and an amino acid preparation was similar in both groups. One infected and two uninfected donors were found to have developed mild hydroureter and hydronephrosis on excretory urography. Schistosomiasis did not significantly affect compensatory hypertrophy of the remaining kidney. We conclude that uncomplicated schistosomiasis in living kidney donors does not adversely affect either the function or the morphology of the remaining kidney, at least during an observation period of up to five years. Schistosomal infection does not seem to alter the adaptive changes in the remaining kidney, provided that the donor had functionally and morphologically intact kidneys and that the schistosomiasis was treated before kidney donation. Longer term evaluation is recommended, however, to confirm the validity of these observations. PMID- 1292082 TI - Safety aspects and diagnostic findings of serial renal allograft biopsies, obtained by an automatic technique with a midsize needle. AB - Percutaneous biopsy is an important diagnostic procedure in evaluating the renal allograft with compromised function. Graft losses and haemorrhagic complication are major risks. To minimize these problems we used a midsize TruCut needle, controlled by an automatic firing device (Biopty-Cut), fixed to an ultrasound guidance system. Core biopsies of 1.2 x 20 mm were obtained from 1,421 kidney grafts. On 5 occasions a haemorrhagic complication that required prolonged hospitalization or intervention occurred. No grafts were lost as a consequence of the biopsy procedure. Typical histological morphological parameters found during allograft rejection has earlier been established. Using a protocol with 27 histological parameters this study confirms that recognized criteria for rejection can be relied upon even with this smaller needle. The results showed that the degree of oedema and lymphocytic infiltration of the interstitium and in the arterial wall discriminated best between rejecting grafts and non-rejection grafts. PMID- 1292083 TI - Renal abscess complicating renal abnormalities in tuberous sclerosis. Case report. PMID- 1292084 TI - Say it isn't so... PMID- 1292085 TI - Self-care assessment tool for spinal cord injured persons. AB - The purpose of this study was to develop a reliable and valid tool that assesses the cognitive and functional skills needed for self-care in persons with spinal cord injury (SCI). The Self-Care Assessment Tool (SCAT) assesses cognitive and functional skills in eight self-care areas: bathing/grooming, nutritional management, taking medications, mobility/transfers/safety, skin management, bladder management, bowel management and dressing. The tool was carefully developed and has demonstrated content validity. Interrater reliabilities for the cognitive, functional and total scores ranged from .69 to .94 (n = 10). Test retest reliabilities for the cognitive, functional and total scores ranged from .06 to .86 (n = 14, 16). Regarding predictive validity, R2 ranged from .61 to .90 for the cognitive, functional and total scores (n = 18). Although continued reliability and validity studies are needed, the SCAT has potential to measure patient rehabilitation outcomes, to evaluate nursing care approaches and to serve as a quality assurance indicator for nursing care. PMID- 1292087 TI - What is the best transportation for a person without head control? PMID- 1292086 TI - The arduous road to recovery. AB - The transition from acute rehabilitation to life in the community represents a new experience for the person with a spinal cord injury (SCI). After returning home, the person is required to manage a range of new challenges created by the injury and its consequences. There is a paucity of information regarding the practical aspects of persons with SCI attaining educational goals and full-time employment. Considerations such as emotional/social adjustment, support systems, physical and attitudinal barriers, work disincentives, and health care needs must be addressed. This article illustrates how one person with quadriplegia overcame obstacles and barriers in his quest to obtain a college education and gainful employment. The experiences of a young man with quadriplegia, as well as a nursing perspective, are presented. Key aspects are identified and related to nursing practice. Stages of adult development, education, and practical considerations are also examined. PMID- 1292088 TI - [Psychodynamics of perversions]. PMID- 1292089 TI - [Management of perversions]. PMID- 1292090 TI - [Pedophilia and perversions]. PMID- 1292091 TI - [Perversions]. PMID- 1292092 TI - [Children who are victims of sexual abuse]. PMID- 1292093 TI - [Difficulties of management. A clinical case]. PMID- 1292094 TI - [The nursing relationship confronted with perverted acts]. PMID- 1292095 TI - [Lise]. PMID- 1292096 TI - [Confidant, messager of the gods]. PMID- 1292097 TI - [A brief and recurrent violence]. PMID- 1292098 TI - [Anomalies of sexual conduct. Definitions and classifications]. PMID- 1292099 TI - [Nursing story. It is not dangerous]. PMID- 1292100 TI - [Research--patients as research subjects]. PMID- 1292101 TI - [Joint leadership education]. PMID- 1292102 TI - [Postpartum crisis--when Marianne became psychotic. Interview by Mette Fjordbo]. PMID- 1292103 TI - [Postpartum crises--collapse of the capable young woman]. PMID- 1292104 TI - [Drug information. Fish oils can make big babies]. PMID- 1292105 TI - [Clinical nursing. One and a half years with liver transplantations]. PMID- 1292106 TI - [Work environment. Nurses need psychological support]. PMID- 1292107 TI - [Work environment. They are in need of help. Interview by Anne-Mette Riis]. PMID- 1292108 TI - [White fear]. PMID- 1292109 TI - [Relief for the soul]. PMID- 1292110 TI - [Schizophrenia. Network bases--a new type of institution]. PMID- 1292111 TI - [Nutrition information. Fat, cholesterol and ghetto culture]. PMID- 1292112 TI - [Continuing education--cancer patients are found everywhere]. PMID- 1292113 TI - [ICN--international congress now open for everyone]. PMID- 1292114 TI - [Instruction can save health expenses]. PMID- 1292115 TI - [Nursing story. When the magnolias bloom]. PMID- 1292116 TI - [Initial experience with the clinical use of intravascular ultrasonic scanning in general angiography]. PMID- 1292117 TI - [Clinical variants of the acute course of common variable immunodeficiency]. PMID- 1292118 TI - [The treatment of the therapeutic patient: contradictions and errors]. PMID- 1292119 TI - [Sudden cardiac death (a review of the literature, problems for discussion and the author's own observations)]. PMID- 1292120 TI - [Lipoprotein(a)--a risk factor for coronary atherosclerosis]. PMID- 1292121 TI - [Late ventricular potentials in the assessment of electrical instability of the myocardium in acute forms of ischemic heart disease]. PMID- 1292122 TI - [The mechanisms of a disorder of the respiratory movements in diseases of the respiratory and circulatory organs]. PMID- 1292123 TI - [The combined and isolated effects of arterial hypertension and hypercholesterolemia on the late prognosis of patients with stenocardia (based on the results of 26 years of prospective observations)]. PMID- 1292124 TI - [The criteria for a differentiated approach to using hemosorption and plasmapheresis in the combined treatment of progressive stenocardia]. PMID- 1292125 TI - [The characteristics of segmental contractility in patients with an acute myocardial infarct at different times of physical activation]. PMID- 1292126 TI - [Early physical rehabilitation and its neuroendocrine support in myocardial infarct patients]. PMID- 1292127 TI - [The pathogenesis of chronic inflammation]. PMID- 1292128 TI - [The assessment of the effect of a change in the frequency of continuous electrocardiostimulation on the indices of central hemodynamics and myocardial contractility using the method of radionuclide ventriculography]. PMID- 1292129 TI - [The characteristics of the changes in the renin-aldosterone system, prostaglandins and cyclic nucleotides of patients with a fatal outcome against a background of chronic heart failure]. PMID- 1292130 TI - [The ultrasonic assessment of heart function and pressure in the pulmonary artery of patients with rheumatic diseases]. PMID- 1292131 TI - [The characteristic cytological, immunological and biochemical changes in the synovial fluid in synovitis of different etiologies]. PMID- 1292132 TI - [The prostaglandin-prostacyclin system and thrombocyte functions in patients with systemic lupus erythematosus]. PMID- 1292133 TI - [Thrombocyte survival in blood diseases]. PMID- 1292134 TI - [The use of autotransfusions of photo-modified blood in the combined treatment of hematology patients]. PMID- 1292135 TI - [The radionuclide content of the feces of people working in the area of the Chernobyl Atomic Electric Power Station in 1986-199)]. PMID- 1292136 TI - [Bivalent cations of the bronchial contents in the pathogenesis and clinical picture of bronchial asthma]. PMID- 1292137 TI - [The clinical manifestations of bronchial asthma]. PMID- 1292138 TI - [The effect of pelotherapy on the external respiratory function of patients with pulmonary tuberculosis]. PMID- 1292139 TI - [The pulmonology of disasters]. PMID- 1292140 TI - [The nitrate withdrawal syndrome. A review of the literature and the data from the authors' own research]. PMID- 1292141 TI - [The clinical course of paroxysmal reciprocal atrioventricular tachycardias under long-term prospective observation]. PMID- 1292143 TI - [Psychogenic disorders in patients on hemodialysis treatment]. PMID- 1292142 TI - [The effect of nitrosorbide, korinfar, obzidan and spesikor on cardiovascular function in a right bundle of His block]. PMID- 1292144 TI - [The aerobic-anaerobic transition as an index of tolerance for physical loading in morbidly obese patients]. PMID- 1292145 TI - [Blood volumes in patients with chronic glomerulonephritis]. PMID- 1292146 TI - [A renal mask of melanoma]. PMID- 1292147 TI - [A case of the Ehlers-Danlos syndrome complicated by massive hemorrhages]. PMID- 1292148 TI - Internal resorption: a case presentation with bruxism as the possible etiology. PMID- 1292149 TI - The new Texas insurance laws: relief for the Texas dentist. PMID- 1292150 TI - Orthodontic treatment of a Class II division 1 malocclusion exhibiting significant maxillary arch length deficiency: a case report. AB - The orthodontic correction of a Class II Division I malocclusion with significant maxillary arch length deficiency and a blocked-out maxillary cuspid is reported. The case was successfully completed on a non-extraction basis using extraoral cervical headgear anchorage and compressed coil springs to gain necessary maxillary arch length. No intermaxillary elastics or functional appliances were used. Favorable patient cooperation and facial growth were instrumental in achieving good results. PMID- 1292151 TI - [Empirical approaches to epidemiology of the Middle Ages]. AB - Diseases result from hazards and influences originating in one's environment and could be described in evolutionary terms as maladaptations. Variations in the pattern of diseases throughout times and places can therefore indicate variations in the living conditions of ancient populations. Palaeopathology is the only way of gathering empirical data suitable for the reconstruction of epidemiological developments in the past. In spite of an abundance of material from the middle ages, only 25 series turned out to fulfill two crucial prerequisites, a certain minimal sizes and a palaeopathological analysis. Still a statistical comparison of those palaeopathological analyses proved impossible, because in most cases only casuistic details were available. This deficiency results from a lack of concept within palaeopathology. The ecosystem theory offers a basis for the development of a far-reaching concept. Widely accepted paradigms are indispensable for a prolific interdisciplinary cooperation on the highly relevant and complex phenomenon disease. Working with a standardized concept palaeopathology will be able to contribute to the solution of questions central to both, social history and environmental archaeology. PMID- 1292152 TI - [Approaches for identifying the functional application of Greek-Roman medical instruments]. AB - Various approaches may be used in attempting to identify ancient medical instruments in cases where documentary or archaeological evidence fails to provide adequate information about their appearance or application, viz.: 1) the etymological approach, which is appropriate when only the instrument's name is known and when this indicates something about its form or function. 2) the philological approach, involving a Constitutio textus, the etymological analysis of the instrument's name and an examination of parallel references. This method is suitable in the case of instruments described in an ancient medical text whose meaning is not completely clear. 3) the philological-technical approach, which attempts an interpretation using the above philological approach supplemented by a consideration of the present-day function of a particular instrument or procedure. 4) the technical approach, which may be useful either when the existence of specific variants of an instrument has already been reliably established by means of appropriate technical terms or archaeological evidence and when the instrument is designated in the next in question only by some generic term, or alternatively when terminological specifications are lacking but the available archaeological evidence points to the existence of variants of an ancient instrument adapted for specific ends. For the purpose of illustration, the approaches described here will be applied to problem cases. PMID- 1292153 TI - ["Preformation and prediction" of the human sex. Wilhelm Weinberg's critique of Otto Schoner's "theory"]. AB - In 1909 Otto Schoner, a district medical officer, claimed human sex to be determined by ovarian preformation and to be precisely predicted. Up to his death in 1940 Schoner denied not only the role of sex chromosomes, but chromosomes as carrier of heritage in general. His "theory" of sex preformation in the human ovary and sex prediction was published in renowned journals, e.g. "Zentralblatt fur Gynakologie" and "Zeitschrift fur Geburtshilfe und Gynakologie". His statistics as well as the "theory" were criticized by Wilhelm Weinberg, a general practitioner, obstetrician and statistician. Weinberg's name has been firmly linked to a principle of population genetics by the eponym "Hardy-Weinberg-law". This paper is intended to give an extensive description of the controversy between Schoner and Weinberg. PMID- 1292154 TI - [Microscopic anatomy from the viewpoint of the macroscopic anatomist: the Vienna anatomist Joseph Hyrtl and his microscopic injection specimen]. AB - Mainly due to an intellectual opposition to microscopy the promising early investigations in this field had come to an untimely end resulting in a neglect of the microscope during the 18th century. In this situation micro-injected specimens were to become an important link on the way to the microscopical science of histology establishing in the first half of the 19th century. Starting without optical instrumentation on the solid grounds of visual experience injected vessels and ducts provided a pathway from well known macroscopical into unknown microscopical dimensions. Without changing their level of perception anatomists could look through a microscope with macroscopist's eyes. Under this aspect Joseph Hyrtl's specimens are not part of a systematic microscopic anatomy or histology but technically demanding preparations to study body morphology and function by comparative anatomy. PMID- 1292155 TI - [Human abnormalities--their importance in the world view during antiquity and the early Middle Ages]. AB - In consideration of the experience that also in our present day society the development of a handicapped baby is understood by some as the visible result of a morally guilty behaviour of the parents, the present study raises the question, whether the identification of physical appearance and moral attitude has been in a certain historical epoch the preferred approach in science for understanding the origin of human malformations. After the treatment of the teratological theories in greek medicine and aristotelian natural philosophy the question of the origin of human malformation is examined in Pliny's "Historia naturalis" and Augustine's "De civitate dei". A comparison between the theories presented shows that the moral interpretation of human malformation is an inevitable consequence of the augustinian theological thinking. PMID- 1292156 TI - [Virchow as politician and the Berlin Society of Obstetrics in 1848]. PMID- 1292157 TI - [The characteristics of chromosomal distribution and of the variability of the multiply repeating DNA fraction of the genome in Bos taurus L]. AB - The uniform distribution of satellite DNA II and IV has been revealed using in situ hybridization and differential staining in centromeric regions of autosomes. The sex chromosomes have not found such nucleotide blocks. There is only minor satellite IV block inside Y chromosome short arm. The Y chromosome has got some (TG)n enriched blocks distributed also among other parts of genome and one copy of sequences like human ZFY gene. The high repetitive fraction of bovine genomic DNA have not revealed RFLP. However, the difference has been found by blot hybridization between genomic organization of satellite IV in cattle and yak chromosomal DNA. Non-Mendelian distribution of some such nucleotide blocks has been obtained for interspecies crosses of cattle and yak. PMID- 1292158 TI - [The function of alloantigens in the animal organism]. AB - Spread of alloantigens in the animal organism is shown. Alloantigens play a great role in cellular differentiation, intercellular interaction and regulation of immune response. The substances, the cell interacts with, are selected using restrictions, that exerts an influence on regulation of gene expression by feedback principle. PMID- 1292159 TI - [Polyploidy and deviations in the gonadal morphology of tetraploid toads, Bufo danatensis (Amphibia: Anura: Bufonidae)]. AB - Morphological features of gonads of diploid Bufo viridis and tetraploid B. danatensis from 15 localities of USSR (453 spec.) were investigated. Females with the rudimentary ovaries were found among polyploid toads from south Turkmenia. The toads from Tajikistan having the external features of males usually demonstrated a specific kind of lateral gynandromorphism: a single side testes and rudimentary ovaries (with the normal ovarioles). The observed facts are treated either as a result of hybridization of recent species or as a result of originality of genomes organization. PMID- 1292160 TI - [The genetic aspects of phylogeny in the brown Carpathian cattle of Ukraine]. AB - The results of studies of special features of the genetic structures of grey brown Carpathian cattle in its ecological recess are presented. The immunogenetic resemblance and distance between related and unrelated breeds of grey-brown Carpathian cattle were calculated. It was found, that grey-brown Carpathian cattle were genetically most similar to Swiss (r = 0.9067) and unsimilar to Herefords (r = 0.7457). It was shown, that the grey-brown Carpathian cattle had unique traits of the genetic structures for B-system of erythrocyte antigens. PMID- 1292161 TI - [The characteristics of the reproductive capacity of hybrids of banteng (Bos (Bibos) javanicus d'Alton) with the domestic cow (Bos (Bos) primigenius taurus)]. AB - The hybrid progeny of F1 produced by crossing of banteng and domestic cow is characterized by absolute sterility of the male line and fertility of the female line. The crossbred males become fertile in further progenies while crossing cross-females with males of initial forms. Successful use of inter-subgenetic hybrids of banteng and domestic cow in selection work is hindered by pathological deviations in their genitals structure as well as frequent deaths of the embryos and foetus in hybrid cows at the different stages of embryogenesis. It is suggested that those deviations (both in cow and in bulls) are caused mainly by genetic and immunological factors and are determined to a greater extent by combination of parental couples. PMID- 1292162 TI - [Chromosomal anomalies of human gametes and intrauterine selection. Research on female gametes]. AB - The results of cytogenetical analysis of human oocytes are summarized. The chromosomal disorders in human gametes and in spontaneous abortions are comparatively analyzed. PMID- 1292163 TI - [The cytogenetic indication of irradiation in persons exposed to the action of the factors in the Chernobyl accident]. AB - 363 men who have been working under conditions of additional irradiation in terms from few hours to some months were cytogenetically examined to define individual irradiation. In 111 men with the known dose of irradiation (5-140 cGy), the results of cytogenetic evaluation indicated, as a rule, a less intensive irradiation than physical dosimetry. This could be caused by elimination of chromosome aberrations, individual sensitivity, peculiar irradiation situation, or in some cases by incorrect evaluation of dose. In 252 men with the unknown dose of irradiation a tentative level was determined as based on frequency of metaphases with chromosome type aberrations. According to the study the absorbed dose was below 25 cGy in 209 cases, 26-50 cGy in 39 cases, and reached 51-90 cGy in 4 cases. PMID- 1292164 TI - [The clinico-genetic aspects of mental retardation related to the fragile-X chromosome]. AB - This review deals with main problems of syndrome of X-fragile chromosome. The history of discovery and subsequent study of diseases as well as methods of examination, main clinical symptoms, methods of treatment and prophylaxis have been described. Some hypotheses, explaining complicated mechanism of fra-X syndrome inheritance are discussed. The recent achievements of molecular and genetic investigations of mental backwardness, associated with X-fragile chromosome are included in review. PMID- 1292165 TI - [The interrelation of the antimutagenic action of mannitol to its effect on cellular metabolic processes]. AB - The mannitol influence on mutagenesis of ionizing radiation and cyclophosphate has been studied in albino mongrel rats using the methods of genetic and biochemical analysis. N correlation is determined between antimutagenic action of this preparation and a decrease of malondialdehyde content in cells and free fractions of matrix lysosomes (beta-galactosidase; N-acetyl-beta-D glucosaminidase) and firmly membrane-structurized microsomal (glucose-6 phosphatase) enzymes, whose level increases under the influence of mutagens. It is shown that, one of the way of antimutagenic actions of mannitol is connected with mutagenesis correction at the stage of origin of mutagenic products and their transport to chromosome DNA. PMID- 1292166 TI - [The effect of administration of non-soluble fungal glucan on the level of delayed skin hypersensitivity and phagocytic activity of leukocytes in the blood of calves]. AB - The level of delayed skin hypersensitivity (DSH) was evaluated in vivo after dinitrofluorobenzene induction (3rd and 7th week of the experimental) while the level of phagocytic activity (FA) of blood leucocytes (in weekly intervals during six weeks of observation) was evaluated in calves (4.5 to 5.5 months of age) after administration of particular fungal glucane (from oyster mushroom) at a dose of 10 mg/kg live weight. In calves which were administered glucane (abbr. G), a significantly stronger cell-mediated immune response was recorded by means of DSH test in the 3rd week of observation, namely in comparison with its starting value (P < 0.01) and also with the value of control animals (P < 0.01; K group)-Tab. I. In the seventh week of the experiment there was not a statistical difference in the average values of DSH any more (Tab. I). But at that time 100 percent of calves showed a skin reaction above 6.5 mm (mean = 7.64 +/- 0.55) evoked by the used sensibilizer in the G group; this reaction was significantly higher (P < 0.01) in comparison with the value of DSH in a majority (80%) of calves of the K group (mean = 6.15 +/- 0.21)-Fig.1. The immunostimulating effect of the used glucane on the FA of blood leucocytes was less significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292168 TI - [Relation of lactose levels in milk and indicators of mammary gland health in the first third of lactation]. AB - A total of 662 bucket milk samples from cows of two breed groups were examined: red and white breed = Bohemian Pied cattle with different genetic proportions of Ayrshire and Red Holstein improvement breeds; black and white breed = Black and White Lowland breed and different degree of absorptive crossing with a genetic proportion of the Holstein breed. Samples of daily milk yields were taken in the first three months of lactation once a month within a year. A possibility of using lactose content as an auxiliary indicator for detection of the mammary gland secretion disorders in the initial lactation stage was evaluated. The average values of the different indicators and their variability are summarized in Tab. I showing also the significance in a statistical model of included effects. Lactose content (L) was 4.88 +/- 0.20%, chloride content (Cl-) 113.7 +/- 22.4 mg/100 ml, somatic cell (SC) count 474 +/- 805 thousand/ml, SC count log corresponds to the geometrical mean of 234 thousand/ml, titratable acidity (SH) 7.34 +/- 0.83 x 2.5 mmol/l, chloride-lactose ratio (ClL) 2.27 +/- 0.51, conductivity (gamma) 442.4 +/- 34.5 mS/m and mastitis test (MT-NK) 0.72 +/- 1.18. The efficiency of the used statistical model was highest for Cl- content (Tab. I, R2 = 0.41), and it was lowest for SC counts (R2 = 0.07), while it increased to the twofold value (R2 = 0.15) after logarithmic transformation of SC counts. The breed group exerted a significant effect on Cl-, SC, log SC, SH, ClL, gamma and MT-NK (Tab. I). The breed group of red and white cows (Tab. II) had higher component contents and better indicators of the udder health state (Cl-, SC, log SC, ClL, gamma and MT-NK). The month of lactation influenced significantly SC, log SC, SH and gamma (Tab. I). A decrease in SC counts with the accruing month of lactation was observed (Tab. II), the trend of gamma and SH was opposite. The effect of lactation number was found to be significant for L, SC, log SC, SH, ClL, gamma and MT-NK (Tab. I). A tendency of a gradual decrease with the lactation number was observed in these indicators: L, SH, proteins and solids-non fat (Fig. 1), while Cl-, gamma and ClL showed an opposite tendency. The year season influenced significantly L, log SC, SH, ClL, gamma and MT-NK (Tab. I, Fig. 2).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1292167 TI - [The effect of administration of vitamin E on levels of serum immunoglobulins and levels of phagocytic activity]. AB - The effect of peroral administration and parenteral implantation of vitamin E was followed as exerted on the concentration of total serum immunoglobulins and phagocytic activity of blood leucocytes in calves. Twelve calves at the age of maximally 14 days with the average live weight of 41.2 kg were included in an experiment with peroral administration; six of them were given Combinal E (Tocoferolum aceticum 40 mg in 1 ml) at a dose of 20 mg tocopherol acetate per kg live weight. Sixteen calves at the age of three months and with the average live weight of 112.6 kg were included in the second trial. The Erevit preparation was implanted intramuscularly to eight calves at the same dose as in the first experiment (Tocoferolum aceticum 300 mg in 1 ml solutions oleosae). The animals of control groups in both experiments were administered sunflower oil as a placebo, namely at the same amount as the above-mentioned preparations (no oil treatment for peroral administration, heat and pressure treatments of oil for intramuscular implantation). All the preparations lead to a significant increase in vitamin E concentrations in the blood plasma of calves in both experiments, the highest average level being recorded in 24 hours after administration (8.05, and/or 5.51 mumol/l; Tabs. I and IV). The level of total serum immunoglobulins was not influenced by vitamin E supplementation; this level remained below the physiological range of values in calves with peroral administration during the whole time of observation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292169 TI - [Functional liver disorder in relation to decreased titratable acidity of milk]. AB - The internal environment of 17 dairy cows was observed by help of 23 variables of metabolic profile in blood and milk at lowered titratable acidity of milk (Tab. I) Average values of the observed variables were compared with reference values in a histogramme (Fig. 1). We calculated the statistical significance of differences of arithmetical means from reference average. Using correlation analysis we calculated the correlation coefficients for the observed variables. We represented the chosen correlation relations in correlogrammes (Fig. 2). We found significant correlation relations between AST and titratable acidity (degrees SH) (r = 0.791), AST and milk pH (r 0.617), AST and lactose (r = 0.69), AST and glucose (r = -0.56), blood pH and milk pH (r = -0.608), milk pH and lactose (r = -0.89). Mutual relations of titratable acidity with chosen variables of blood serum and milk were evaluated by help of regression coefficients, calculated for each parameter from the mathematical model (Fig. 3). The nearest relations were found for blood pH (regression coefficient /k/ kPH = -11.9), for AST (kAST = -3.1), for milk pH (k milk pH = -1.72) and for Mg (k Mg = -1.98). We also compared the recorded results of titratable acidity with theoretical values of titratable acidity calculated from the mathematical model (Tab. II). The differences between them were not statistically significant. It is evident from the results that the acid-base balance and functional liver condition influence the titratable acidity of milk. PMID- 1292170 TI - [Biochemical aspects of the toxic effects of Supermethrin and the histochemical activity of alkaline phosphatase, acid phosphatase and non-specific esterase in subchronic poisoning in sheep]. AB - Fifteen Slovak Merino sheep were included in the experiment. The animals weighing 21-28 kg were divided into three groups per five animals. In a six-week feeding experiment the animals of group I were given 50 mg supermethrin per kg live weight per day while those of group II received 200, and from week four of the experiment 300 mg supermethrin per kg live weight per day. During the experiment changes of aspartate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2), acetylcholine esterase (EC 3.1.1.7), urea und creatinine levels in blood serum were observed. Six weeks after supermethrin treatment the sheep were slaughtered and histochemical evaluation of alkaline phosphatase (EC 3.1.3.2), acid phosphatase (EC 3.1.3.1) and non-specific esterase (EC 3.1.1.1) was carried out in liver, kidney, duodenum, jejunum and ileum. In the course of the experiment changes of the enzymatic activities of aspartate aminotransferase observed in both experimental groups of sheep were similar to those seen in the control group of animals (Tab. I). As compared to the starting values, no significant changes in the activity of alanine aminotransferase were observed in group II of the experiment and in the controls. However, a significantly decreased alanine aminotransferase activity could be seen in the blood serum of sheep of group I (Tab. II). In both experimental groups of animals no significant changes in the acetylcholine esterase could be seen (Tab. III). As compared to the starting values, no significant changes were observed in creatinine levels of the control and the 1st experimental group of sheep (Tab. IV). In the sheep of the 2nd group a temporary significant decrease (p < 0.05) in creatinine levels was seen. The dynamics of urea levels was similar to starting values in all animals throughout the experiment Tab. V). In the control group of animals (Fig. 1) the high density of reaction product of alkaline phosphatase was determined in the microvilli of enterocytes of the small intestine. In the small intestine of the animals of both experimental groups, the activity of this enzyme was shown to be located in the same zone (Fig. 2). In all experimental animals in the parenchyma of the liver and kidney no significant changes could be observed. In both experimental and control animals the high activity of acid phosphatase was demonstrated to be located especially in the cytoplasma of enterocytes. The activity of non-specific esterase was located in the cytoplasma of enterocytes of the small intestine, in the intestinal crypts its activity was slight up to high.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1292171 TI - [The effect of bentazone manufactured in Czechoslovakia on the synthesis of bacterial proteins in the rumen of sheep]. AB - The effect of the perorally ingested pesticide bentazone (195 mg.kg-1) of Czechoslovak origin on the amino acid composition of proteins of bacteria adhering to the ventral and dorsal ruminal wall investigated in six sheep. Proteosynthesis of adherent bacteria was studied by a modified and quantified elution method (elution of bacteria by an isotonic buffered solution at 4 degrees C). By the latter, a concentrate of undamaged bacteria a adhering to the sheep ruminal epithelium could be obtained. The yield of the method was estimated by scanning electrone microscopy and it was 93.3% (Legath et al., 1990). The high correlation coefficient (r = 0.94, p < 0.01) suggested that in comparison with the control group of sheep, bentazone in the diet did not have a marked effect on the amount of amino acids in hydrolyzates of bacteria adhering to the dorsal and ventral ruminal epithelium. From the analysis of the single amino acids, it however follows that bentazone in the feeding ration caused significant changes in the concentrations of some amino acids in the proteins of bacteria adhering to the epithelium in the ventral and dorsal part of the rumen (p < 0.05) (Tab. I, II). In both topographico-anatomical parts of the rumen phenylalanine levels significantly increased whereas those of alanine and glycine decreased (Fig. 1). Pesticides can be one of the factors that negatively affect the biosynthetic processes in the rumen of ruminants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292172 TI - [Arbovirus antibodies in wild game caught in Moravia]. AB - The HIT method was used to examine blood serums of the game in Moravia (roebuck, red deer, fallow deer, mouflon, wild boar, brown hare) for the presence of antibodies to arboviruses of these groups: alphavirus (Sindbis-SIN), flavivirus (West Nile-WN), tick-borne encephalitis (TBE) and Bunyamwera (Tahyna-TAH, Calovo CVO). Antibodies to all viruses were detected, and namely in these frequencies: SIN 0.9%, WN 16.9%, TAH 41.5%, CVO 23.1% and TBE 8.5%. PMID- 1292173 TI - [Dynamics of methemoglobin levels in the blood of calves in relation to the ingested quantity of nitrates and the transrenal transport of nitrates]. AB - Changes of methaemoglobin levels were investigated in the blood of suckling calves. Transrenal passage of nitrates was determined in dependence on the ingested amount of nitrates. The experiments were conducted under defined husbandry conditions; no excessive nitrate and nitrite supplementation of the calves by feeds and water could be stated. Imitation of possible field conditions when mainly water, but feeds too, may contain higher nitrate and nitrite levels, was carried out by peroral administration of an aquaeous solution of KNO3 to calves. The administered dose was increased from one to 2, 5 and 10 g per animal and day, respectively, in weekly intervals. MtHb determination in the blood of experimental calves on day 1 and 5 of the administration of 1 g KNO3 revealed no significant values. On day 1 and 5 of the administration of 2, 5 and 10 g KNO3 per animal and day, respectively, a significant increase of MtHb levels in the blood of calves was observed 2 and 3 hours after administration, followed by a decrease 4 hours after administration. The maximum values of MtHb in the blood of experimental calves, observed 3 hours following application of the respective KNO3 dose, were within the tolerance limits of the reference values. In urine, 3 hours after the administration of 10 g of KNO3 a mean nitrate value of 941.40. PMID- 1292174 TI - [The effect of monensin on performance and selected biochemical and hematological parameters in the blood of calves]. AB - The aim of this study was to find out the influence of monensin, a ionophore antibiotic, on calf performance and selected physiological parameters. Monensin is a product of Streptomyces cinnamonensis. It has effects on all Gram-negative microbes, such as Escherichia coli, salmonellas, pseudomonads and vibria. It has a small effect on Gram-positive microbes. At the beginning of the experiment eight young crossbred bulls (C x N) at the age of three weeks were weighted and divided into two groups, experimental and control ones. Calves were kept in individual boxes and fed acidified whole milk (2 ml of 85% formic acid per 1 litre of milk). They had a free access to concentrates (COT), hay and drinking water. The calves received 3 lt. of whole milk twice a day until the age of eight weeks. 0.5 mg of monensin per 1 kg live weight were served orally to calves of the experimental group every day. Monensin was made by the Spofa Corporation, Prague. Daily intake of feed was recorded and the calves were weighted once a week. Blood samples were taken from the jugular vein before the beginning of the experiment, and in the period from the fifth to the tenth week of age, always before morning feeding. The average daily live weight gain was 0.452 kg and 0.471 kg for the control and experimental group, respectively, during the milk feeding period, the index being 104.2 (Tab. I). Tab. II shows the average feed intake per 1 kg live weight gain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292176 TI - [Seasonal dynamics of the occurrence of parasites in the digestive tract in poultry]. AB - The extensity of digestive tract infection with different parasites in domestic fowl kept on large and small farms was diagnosed in individual months of the years 1986-1989. The obtained results were confronted with the values of average monthly temperatures and rainfall sums in individual months of the above mentioned period. The numbers of birds examined in individual months of the years 1986-1989 were as follows: 105 to 234 from large farms and 32 to 112 from small farms. The numbers of examined chicks from small farms were lowest in winter, and on the other hand highest in summer. The numbers of examined fowl from large farms varied from month to month. Particularly Coccidia (average extensity 12.1%), scarcely Heterakis gallinae (0.2%) and Capillaria spp. (0.1%) were detected in birds kept on a large scale. The occurrence of Coccidia fluctuated from 5% in birds dissected in May, July and November to 22% in birds dissected in August. H. gallinae and Capillaria spp. occurred rarely, namely in the second half of the year after warm and rainy periods (Figs. 1 and 2). The occurrence of gastrointestinal parasites in domestic fowl kept on small farms is variable within the year while the change begins in summer and culminates in autumn after warm and rainy months. Only following the sporulation of larger numbers of oocysts, or the maturation of larger numbers of eggs or cysticercoids their pathogenicity can play a key role while their concentrations in the environment are increasing. Hence parasitoses begin to appear after the rise of temperatures and rainfall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292175 TI - [Verification of the usefulness of Estrophan inj. Spofa in the control of reproductive parameters in sows after weaning of piglets]. AB - Cloprostenol, a prostaglandin F2-alpha analogue, used in the Czechoslovak preparation Oestrophan ing. Spofa was tested by a new nontraditional use. The effect of cloprostenol use on reproductive parameters of sows after piglet weaning was followed in a set of 456 experimental and 434 control sows. The effect of single intramuscular instillation of cloprostenol was tested in five partial observations: to multiparous sows at a dose of 175 micrograms on the day of weaning (experimental group no. 1), on day 1 after weaning (group no. 2), 500 micrograms on day 1 after weaning (group no.3), to primiparous sows at a dose of 500 microgram on day 1 after weaning (group no. 4). The treatment used in group no. 4 was also applied to 42 primiparous sows kept on a farm with regular occurrence of post-weaning anoestria of sows (experimental group no. 5). These parameters were evaluated: dynamics of oestrus onset within five, and/or ten, days after weaning, average length of the weaning--first insemination interval, conception rate after the first insemination in dependence on terminated deliveries and parameters of piglet litter. Cloprostenol application did not have a statistically significant effect on the evaluated reproductive parameters. The percentage of multiparous, and/or primiparous, sows in which the oestrus onset was not detected by the 10th day after weaning, did not show any large differences in the various experimental and control groups (17.09 vs. 16.55%, 23.53 vs. 32.56%, 13.66 vs. 18.13%, 29.54 vs. 30.30%; P > 0.05). On the farm with regular occurrence of post-weaning anoestria there were 73.81% of primiparous sows with oestrus onset after cloprostenol instillation and 71.43% primiparous sows without treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292177 TI - [Use of monoclonal antibodies against human HLA II antigens for the detection of bovine B lymphocytes and macrophages]. AB - The crossreactivity of mouse monoclonal antibodies (MoAbs) (Tab. I) prepared against human HLA-DR and HLA-DP antigens was studied in various bovine cells: lymphocytes from lymph nodes and peripheral blood, adherent (B) and nonadherent (T) lymphocytes, monocytes, granulocytes and platelets. In the immunofluorescence test, MoAbs Bra13, Bra14, Bra20, Bra22, Bra30, Bra70, HL-38 reacted with bovine B lymphocytes and monocytes, but not with other tested cells (Tab. III, IV). These antibodies, except Bra22, were positive with B lymphocytes in the complement dependent cytotoxic test (Tab. II). The similarity of the bovine antigens and HLA DR antigens determined by used MoAbs was also proved by immunoblotting. Monoclonal antibodies Bra38 and BraFB6 did not react with the bovine cells and separated antigens. The epitope (HLA-DR) recognized by the antibody Bra38 is probably absent in cattle. The presence of HLA-DP analogue determined by the antibody BraFB6 has not been confirmed. The crossreactive MoAbs could be used for the detection of B lymphocytes and macrophages in veterinary immunology. PMID- 1292178 TI - [Selected biogenic elements in the blood of hares (Lepus europaeus Pall.)]. AB - Blood samples were collected through aortic punctures in hares coming from different agricultural regions. Base biogenic elements (Ca, P, Mg, Na, K, chlorides) were determined in blood plasma not showing haemolysis. The values obtained in hares born and kept in captivity are presented for the purposes of comparison. Changes in element levels are described for different pollution load of ecosystems, from physiological aspects for more advanced stages of gravidity, for a higher lactation number and for young growth. The problems of qualitative fasting of hares can also be documented by mineral contents in blood plasma. The levels of some elements were evaluated for a group of adult male and female hares, and the youngs regardless of their sex until the disappearance of Stroh's outgrowth. The results were processed statistically and are summarized in tables (Tabs. 1-12) and they are compared with available literature. PMID- 1292179 TI - [The international exhibition-symposium on the problems of medical and medicotechnical support for rescue services and emergency medical care service]. PMID- 1292180 TI - [The adaptation of servicemen to military service]. PMID- 1292181 TI - [The consequences of the war in the Persian Gulf region (a review of the literature)]. PMID- 1292182 TI - [The optimization of bone repair in open comminuted fractures of the long bones]. AB - Clinical and experimental researches were conducted to study the possibilities for enhancing the efficiency of treatment of open composite comminuted and crushed fractures of long bones with the help of repercussive action of electrets. The results of roentgenomorphometric, clinical and biomechanical researches have shown the efficiency of electrets that could shorten the healing time of the infected wounds, stop the inflammatory reaction and promote the repairing process of bones. The application of electrets using the repercussive methods in complex treatment of complicated open fractures in cases with multiorgan and concomitant injuries creates favourable conditions for the healing process. This method is simple, atraumatic and economical. PMID- 1292184 TI - [The characteristics of the course and treatment of thermomechanical injuries of a moderate degree of severity (experimental research)]. PMID- 1292183 TI - [The therapeutic procedure in acute arterial obstruction]. PMID- 1292185 TI - [The use of solcoseryl during intraoperative hemodilution and in the early postoperative period]. PMID- 1292186 TI - [Disorders of antiviral cellular resistance in acute suppurative-destructive lung diseases]. PMID- 1292187 TI - [The characteristics of the course of reactive arthritis in Afghanistan]. PMID- 1292188 TI - [Ultraviolet irradiation of the blood as a method for the nonspecific therapy of acute pneumonia]. PMID- 1292189 TI - [The prevention of obliteration of the rhinostoma after dacryocystorhinostomy]. PMID- 1292190 TI - [The medical service of the Armed Forces in a unified state system of disaster medicine]. PMID- 1292191 TI - [The clinico-epidemiological characteristics of brucellosis in young people]. AB - The article describes an outbreak of brucellosis among the servicemen (age 19-32) which was caused by Br. melitensis. 13% of servicemen in the military unit went through this disease. This outbreak was caused by unsatisfactorily treated mutton of sheep which were affected with brucellosis. The illness had acute septic course. The appearance of the focuses of disease in locomotor system took place only when the infectious process had a rather long period (septicometastatic course). The acute septic form of brucellosis (minor and middle-gravity cases) was characterized by subfebrile and febrile body temperature, slight intoxication without considerable worsening of health or incapacitation. The application of the modern means of treatment, including immunotherapy, resulted in a rapid coping of the acute course of illness, but the complete recovery was not attained. The convalescents had multiple recidivating (secondary metastatic forms) of infectious process with affections of locomotor, genital, peripheral nervous systems with further development of residual signs. PMID- 1292193 TI - [New aspects of the use of hyperbaric oxygenation in aviation medicine]. PMID- 1292192 TI - [The morphofunctional status of the gastric mucosa in persons exposed to microwave action]. PMID- 1292194 TI - [The prognosis of the professional fitness of sailors for action under extreme conditions]. AB - The researches described in this article made it possible to substantiate a number of important professional qualities of seamen which are indispensable in extreme situations. Three professional categories, namely command duty officers, operators and specialists of the local posts were the matter of these researches. A combination of symptom complexes of individual qualities which predetermines a successful duty performance in extreme situations was disclosed. A complex of valid methods was substantiated for quantitative estimation of individual psychological qualities. On the basis of these symptom complexes the authors worked out the estimation criteria for prognostication of professional ability of seamen to act in extreme situations. PMID- 1292196 TI - [A mounting device for the Linza MT-4 microscope]. PMID- 1292195 TI - [A device for the temporary transcutaneous ligation of the major vessels of the extremities]. PMID- 1292197 TI - [A diagnostic ultraviolet illuminator]. PMID- 1292198 TI - [The problems of a healthy life style in the armed forces of the USA]. PMID- 1292199 TI - [Variants in the deployment of a special-assignment medical detachment]. PMID- 1292200 TI - [The priority trends in fundamental biomedical research]. AB - Priority trends should primarily include wide-scale aimed epidemiological investigation of the population health in different regions of Ukraine, determination of risk factors. This is genetic monitoring of the population, creation of national and regional registers of hereditary and congenital abnormalities. Progress in all medical domains will be promoted by investigations on the molecular and genetic levels. This is evidenced by world experience, achievements of th A. A. Bogomolets Institute of Physiology, Institute of Molecular Biology and Genetics (Acad. Sci., Ukraine), Institute of Gerontology, Institute of Endocrinology, Institute of Occupational Health developing. New apparatus, materials and drugs, technology methods for medicine are developing in many Institutes of physico-technical and chemical specialties (Acad. Sci., Ukraine). This creates new possibilities in the diagnosis, treatment and prophylaxis of diseases. PMID- 1292202 TI - [The prevention of HIV infection in the army and navy]. AB - In the course of 5 years 121 foreign and 13 Soviet military servicemen showed HIV infection; seven of them (officers and warrant officers) are still in service. As distinct from WHO requirements symptomless virus carriers are also registered. Infected servicemen constitute 1.5% from the total number of infected in the country. PMID- 1292201 TI - [The effect of vilozen on the immune status of erysipelas patients and the prospects for its use for the immune rehabilitation of convalescents]. PMID- 1292203 TI - [A cholera outbreak in Nikolaev Province]. PMID- 1292205 TI - [Preclinical trials of polyplatillen, the antitumor activity of a complex platinum compound with DNA on a leukemia P388 model in a HEp-2 cell culture (1)]. AB - The authors studied the antitumour activity of a new complex platinum compound (DDP-DNA) in mice with leukemia P-388 and in cell culture. DDP-DNA was introduced intraperitoneally 24 hours after inoculation of 2 x 10(6) tumour cells. It was established that by its antitumour activity DDP-DNA was not inferior then DDP. The antiproliferative activity of nontoxic doses of the preparation in cell culture has been shown. PMID- 1292204 TI - [The diagnostic problems of systemic diseases in an infectious disease clinic]. AB - Results are reported of a study of 46 patients with systemic diseases: connective tissue, inflammatory granulomatous processes, lymphoid tissue lesions and blood diseases treated in the clinic of infections diseases. Difficulties and errors in their clinical diagnosis, and their causes are shown. It is emphasized that these patients are hospitalized in infections clinics and that the incidence of systemic diseases rises in conditions of radiation environment. PMID- 1292206 TI - [The results of a clinical trial of the new drug agent carbabenzpyride]. AB - Analyzed were results of a clinical use of a new drug carbabanzpyrid in 57 patients as an analgetic, antipyretic, anti-inflammatory, interferonogenic drug. The drug proved effective in the complex treatment of several diseases, accompanied by fever, pain syndromes of different genesis and location, acute respiratory viral infections, active inflammatory processes of different etiology including bronchitis, pneumonia, active rheumatism, arthralgias, myalgias. The drug was of little efficacy in infections-allergic polyarthritis with a marked exudative component. PMID- 1292207 TI - [The structural bases of the cardiotoxic action of the anti-tumor antibiotic carminomycin]. AB - The authors substantiate morphological and structural-functional basis of the cardiotoxic effect of the antitumor anthracycline antibiotic carminomycin after its single intraperitoneal administration in maximum tolerable doses. Results indicate that the cause of development of cardiac failure after administration of carminomycin to experimental animals in the development of an alternative and plastic cardiac failure prevalence of type I. PMID- 1292208 TI - [Experience in using an autovaccine in treating patients with chronic osteomyelitis]. AB - Autovaccine immunization (AI) of 60 patients with chronic osteomyelitis resulted in 93% success (significant in 43%) in formerly failures both with surgical and medical treatment. The method of manufacturing the autovaccine is described, immunization schemes are given. PMID- 1292209 TI - [The working conditions and health status of miners in Donets Basin coal mines]. AB - Data are reported on working conditions of coal miners considering the main physical (dust, noise, vibration, microclimate) and chemical environmental professional factors and their prognosis up to the year 2005. The authors analyze professional morbidity (pneumoconiosis, dust-induced bronchitis, vibration disease, cochlear neuritis etc.) and diseases with temporary loss of the working capacity invalidity and mortality of miners. The relation between working conditions and health status of miners were analyzed. PMID- 1292210 TI - [The work experience of the consultative polyclinic of a provincial hospital under the new economic mechanisms]. PMID- 1292211 TI - [The complications of basic therapy in rheumatology (a review of the literature)]. PMID- 1292212 TI - [The current problems of dietary feeding (a review of the literature)]. AB - Group dietary system is now a disputable problem in medicine. Ukraine shows a tendency in development of universal therapeutic diets with individualization of diets depending on the patient's condition, course of the disease, sex, age etc. Advancements of dietary feeding in the Ukraine should be based on scientific principles. This will promote efficient treatment of the patients. PMID- 1292213 TI - [The differential diagnosis of ecological and professional lung diseases]. AB - Ecological pulmonology appeared due to the technical revolution and increase of toxic substances entering the body through the upper respiratory tract to the lungs. In distinction from professional, ecological diseases are spread among the population in general and not only among those working in conditions of increased professional noxae. PMID- 1292214 TI - [The ecological and hygienic aspects of the use of surface-active substances in oil-producing regions of Ukraine]. AB - Use of surface-active substances (SAS) in the oil-extracting regions of the Ukraine should consider the fact that this is a rather small territory, densely populated, with environmental water and soil problems, significant contamination of several areas by pesticides, mineral fertilizers and complicated by the Chernobyl accidents sequels. SAS may influence the ecological-hygienic balance of the environment, they may enhance migration of many ingredients, increase their toxicity. The authors propose several measures aimed at improving the quality of preventive and actual state inspection over the oil enterprises. PMID- 1292215 TI - [Changes in the low-molecular fractions of physiologically active substances in the tissues of the spleen, lymph nodes and blood serum of rats exposed to x-ray irradiation]. AB - Acute radiation sickness (grades II-III) was induced in experiments on 135 adult rats by single total X-ray radiation (185.7 mCal/kg). A gel-chromatographic study showed that 40 days after irradiation the surviving animals showed a 2 times increase of substances with a molecular mass of 600-850 daltons in the homogenate of lymphoid organs. This possibly evidences their participation in restorative processes. PMID- 1292216 TI - [The interrelation of the secretory activity of the myocardium with its hypertrophic characteristics in patients with ischemic heart disease]. AB - Evaluation of the concentration of atrial natriuretic peptide, angiotensin P, renin activity in the blood of the coronary sinus and aorta in 18 patients with IHD and hypertrophy of the left ventricle during development of induced ischemia revealed that in left ventricular hypertrophy secretion of atrial natriuretic peptide by the myocardium is reduced. The level of this reduction depends on the kind of hypertrophy. Dilatation of the left ventricle cavity furthers exhaustion of the secretory function of the ischemic myocardium. PMID- 1292217 TI - [The efficacy of immunomodulating preparations in treating patients with chronic cholestatic liver diseases]. AB - A study of 102 patients with chronic cholestatic liver diseases revealed that levamisole, T + activin and thymalin possess an immunostimulating effect increasing the level of lymphocytes, T-lymphocytes, activate the functional activity of lymphocytes in patients with chronic cholestatic hepatitis and primary biliary cirrhosis. T = activin, thymalin produce a more pronounced normalization of the immune response by increasing the contents of T-lymphocytes and their subpopulations, elevating the functional activity of mononuclears, reducing the concentration of immunoglobulins, cyclic immune complexes. These changes favour controlling the immuno-inflammatory process in the liver, normalization of clinical manifestation of the disease. PMID- 1292218 TI - [The effect of obzidan and isobarin on the lysosomal apparatus of the neutrophilic granulocytes and on hemostasis under stress factors]. AB - Experiments on rabbits were carried out with the purpose of evaluating the participation of beta-adreno-blockader and sympatholytic agent in the reaction of liberation of lysosomal enzymes of peripheral blood neutrophilic granulocytes in response to the immobilization. It was established that the sympathetic nervous system (via alpha- and beta adrenoreceptors) produces an effect on reduction of the number of lysosomes and liberation of lysosomal enzymes that participate indirectly through factor XII in hemostasis regulation. PMID- 1292219 TI - [A flow cytometric study of the effect of chemotherapy on the lymphocyte population composition in chronic lympholeukemia]. AB - Results are described of a study of the population and subpopulation composition of lymphocytes in the course of use monochemotherapy (MTS) and polychemotherapy (PCT) in 60 patients with the tumorous form of B-cell chronic lympholeucosis using flow cytometric analysis. It was shown that cytostatic treatment in this form of hemoblastosis results in a reduction of the absolute number of B lymphocytes due to reduction of general hemocytosis while the relative content of B-cells remained unchanged in MCT and is increased in PCT. A prolonged scheme of PCT is recommended for clinical use that possesses a distinct antitumour effect as compared with MCT and producing a significantly smaller immunosuppressive effect on the T-cell immune system that other schemes of cytostatic therapy. PMID- 1292220 TI - [Differential diagnostic criteria in chronic myeloproliferative diseases]. AB - A study of functional activity of segmentonuclear neutrophil granulocytes of the peripheral blood in 20 patients with subleukemic myelosis (SLM) and 20 patients with polycythemia vera (PV) revealed in the latter an increase of the functional activity of phagocytosis, oxygen-dependent metabolism and enzymatic activity were more pronounced than in SLM. Nonhomogeneity of morphological and cytochemical indices and patients with SLM and IP may be used as supplementary differential diagnostic criterion in SLM and IP. PMID- 1292221 TI - [The use of lyophilized blood serum for determining the 3-HAA antigen in patients with precancerous diseases and cancer of the bladder]. AB - 3-OAK antigen was determined by immunodiffusion in agar by means of immune sera containing antibodies against 3-OAK. In patients with cancer of the urinary bladder the percentage of detecting 3-OAK-Ag in the native serum was 76.9 while in lyophilized it was 41.9. In patients with pretumorous diseases (leukoplakia, chronic cystitis, papillomas) their values were 64.1 and 56.1 respectively. It is concluded that lyophilized blood serum may be used in the clinical practice for immunological and serological examinations. PMID- 1292222 TI - [The immunodeficiency state and the efficacy of the glucocorticoid therapy of patients with glomerulonephritis and the nephrotic syndrome]. AB - Results are compared of glucocorticoid treatment of proliferative, mesangioproliferative and membraneous types of glomerulonephritis with initial levels of T- and B-lymphocytes. Five types of immunodeficiency states were distinguished different frequency of the latter in various types of glomeruli involvement. It was found that glucocorticoid therapy of nephritis is most efficient in cases when the initial number of T-lymphocytes was within normal limits while the content of B-lymphocytes was increased. PMID- 1292223 TI - [The dynamic mental status of patients who have undergone stereotaxic destruction of the ventrolateral thalamic nuclei]. AB - Examined were 80 patients with parkinsonism and 20 patients torsional dystonia before and after stereotaxic cryodestruction of the ventrolateral thalamic nuclei. A set of tests was used to evaluate attention, memory, associative processes, generalization, comprehension to examine these patients. Only in the group of parkinson patients a reduction of these findings was noted (memory, perception, comprehension). All other mental activity types suffered similarly in all patients after the operations. PMID- 1292224 TI - [The ultrasonic diagnosis of lesions of the hepatobiliary system in protracted forms of viral hepatitis in children]. AB - Ultrasound examination of the hepatobiliary system was carried out in 102 children (3-12 years) with viral hepatitis A and B on the 57-75 days of the disease. Increased liver size and swelling of the parenchyma was revealed in 100% of patients. Thickening of the gallbladder walls was similarly frequent in A and B hepatitis. In 40% deformation of the gallbladder was revealed in 40.1%. The pancreas was increased in 13.6%, indurated in 36.4% of patients. Changes in the gallbladder and cholangitis are clearly related to the level of bilirubinemia ALT activity that is one of the causes of delayed convalescence. PMID- 1292225 TI - [Pulmonary surfactant and its role in the pathogenesis of dust-induced diseases of the respiratory organs in the miners of coal mines]. AB - AIM OF THE STUDY: establishing a relationship between the condition of the pulmonary surfactant and external respiration function in Donbass coal miners with initial and advanced forms of dust-induced lung pathology. One of the early manifestations of lung pathology in miners is increased synthesis and secretion of the surfactant on the alveolar surface with disorders of its functional activity evidencing disorders of lipid excretion from the pulmonary tissue. The presence of albumin in the expired air indicates the presence of alternative processes in the bronchopulmonary apparatus, and highest albumin content in patients with pneumoconiosis and chronic dust-induced bronchitis may be an index of activity of the inflammatory process. PMID- 1292226 TI - [Programming apparatus support of an electrophysiological experiment in hygiene research to set standards for nonionizing radiations]. AB - The authors developed and introduced into practice program-apparatus complex ensuring automation of electrophysiological experiments. This allowed to use neurophysiological methods as an express-analysis with the purpose of substantiating critically limited levels of electromagnetic radiation. PMID- 1292227 TI - [Thermography in the complex examination of patients with skin melanoma]. AB - It is suggested that the thermographic method of examination is most perspective in current diagnosis. It proved very effective in the complex examination of patients with skin melanoma, early tumour metastasis and recurrence of operative treatment. PMID- 1292228 TI - [The naturophilosophical concept of oriental medicine for rational nutrition (a review of the literature)]. PMID- 1292229 TI - [The use of homeopathy in treating diabetics]. AB - The rationale of homeopathic treatment of diabetes mellitus (DM) with constitutional predisposition is discussed. On the basis of a detailed analysis of one case the author describes the method of homeopathic treatment of diabetes mellitus. The treatment is orientated not only on the treatment of DM but also of concomitant diseases with emphasis in the patients constitution. Minimal doses of homeopathic treatment used in 68 patients resulted in a statistically valid stable reduction of hyperglycemia and glucosuria. Stable subcompensation and compensation of DM allowed to decrease the dose of sugar reducing drugs. PMID- 1292230 TI - [The effect of the long-term treatment with calcium antagonists on myocardial function in patients with hypertension]. AB - Prolonged effect (6-12 months) of verapamil and nifedipine on the systolic and diastolic function of the myocardium was studied in 48 patients with hypertensive disease (stage II). It was established that in patients with a high ejection fraction (55% and more) the two drugs produce a distinct reduction of the pumping heart function. The two drugs increase the rate of early diastolic filling. They also may reduce the arterial pressure via different hemodynamic mechanisms: vasodilatation or via reduction of cardiac output. PMID- 1292231 TI - [The functional disorders of the large intestine (a lecture)]. AB - Current ideas on the etiology and pathogenesis of functional disorders of the large intestine are discussed. Their classification, clinical picture, principles of diagnosis and differential diagnosis are outlined with emphasis of the most spread functional diseases of the large intestine: functional (common) obstipation, irritation of the large intestine pruritus ani, insufficiency of anal sphincters, proctalgia. Special attention is paid to treatment (diet, drugs, physiotherapy, spa). PMID- 1292232 TI - [The status of intracardiac hemodynamics and diastolic function in hypertension patients treated with Adverzuten]. AB - Data are reported of changes of the intracardiac hemodynamics, systolic and diastolic cardiac function and their interrelations in the course of treatment of 34 hypertensive patients with adverzuten. Results indicate that the systolic and diastolic cardiac functions did not deteriorate and that reduction of postload was associated with their favourable changes. PMID- 1292233 TI - [The evaluation of the efficacy of obzidan and sydnopharm in patients with stenocardia of effort]. AB - It is concluded that obsidane and sidnopharm were effective in the treatment of patients with exertion stenocardia in outpatients conditions. The patients continued to work. Obsidane treatment was most effective in patients with the hyperkinetic type of circulation, increased blood viscosity and hypercoagulation syndrome. PMID- 1292234 TI - [Experience in the treatment of hypertension patients at a day hospital]. AB - The authors summarize the work a day clinic of a regional cardiological dispensary in the treatment of 152 patients with ischemic heart disease characterized by stenocardia attacks, unstable stenocardia, disorders of the cardiac rhythm, hypertensive crises and other. A positive effect was observed in 94.7%. The economic effect of day-clinic treatment was essential. PMID- 1292235 TI - [The cholecystokinetic effects of Truskavets mineral waters in chronic noncalculous cholecystitis]. PMID- 1292236 TI - [The use of low-energy laser radiation in the combined treatment of patients with chronic lympholeukemia]. AB - Our investigations evidence that intravascular laser radiation of the blood is an effective method of treatment of chronic lympholeucosis. The average hospitalization time became shorter, the period of clinical remission increased. N positive dynamics in the content of beta 2-microglobulin was noted, peripheral blood values improved, the dysbalance of cellular and humoral immunity was controlled. PMID- 1292237 TI - [Calculus formation in the prostate in chronic prostatitis]. AB - The authors examined 350 patients with chronic prostatitis. In 48 (13.7%) of theirs calculi in the prostate were found. The typical clinical manifestations of calculi formation in the prostate, diagnostic criteria and treatment principles developed in the Department of Sexopathology of Kiev Research Institute of Urology and Nephrology are outlined. PMID- 1292238 TI - [Medical deontology in the neurology and neurosurgical clinics]. AB - Deontological problems in neurology and neurosurgery include behaviour of the medical personnel to patients and their relatives, evaluation of the severity of the patients' condition, performance of manipulations and operations, information of the patients about his disease. Deontological problems are of major importance in the adequate treatment of patients with diseases of the nervous system. PMID- 1292240 TI - Metabolic control of eating. PMID- 1292239 TI - [The clinical types of somatization mental disorders in elderly people]. AB - A study is presented of 33 patients suffering of borderline neuropsychic disorders of neurotic and affective levels with somatized course. One should distinguish in these patients mental disorders per se (asthenia, depression and hypochondria) and different functional-somatic, vegetative-vascular and senestopathic disorders and their combinations. Somatized disorders characteristic of this age group were singled out: cutaneous-muscular, abdominal, cerebral and cardiovascular. Cutaneous-muscular were most frequent. The problem is discussed of distinguishing peculiar "senestovegetoses" and "senestosomatoses" in the borders of somatized depressive states. PMID- 1292241 TI - The bioenergetics of obesity syndrome. PMID- 1292242 TI - Energy expenditure and fuel selection in biological systems: the theory and practice of calculations based on indirect calorimetry and tracer methods. PMID- 1292243 TI - Regulation of fatty acid synthase at transcriptional and post-transcriptional levels in rat liver. AB - The regulation of fatty acid synthase in rat liver was investigated at transcriptional and post-transcriptional levels. When rats were fasted for 3 days and refed on a high-carbohydrate diet, the amounts of FAS in liver cytosol began to increase at 12 hours and further increased until 48 hours. The amount of mRNA for FAS began to increase at 6 hours and reached to a maximum level at 12 hours, indicating that the expression of mRNA for FAS precedes the increase of FAS protein pool. After 12 hours the amounts of mRNA gradually decreased and remained at a much lowered level between 24 and 48 hours. The elevated amount of FAS mRNA reflected on the amount of FAS protein in the first 24 hours, but these two parameters were not paralleled thereafter, probably due to the changes in the translational efficiencies. The run-on transcriptional activity of FAS gene began to increase at 4 hours after refeeding a high-carbohydrate diet and further increased to reach a maximum level 25 fold of the initial level at 12 hours, followed by a 16 fold level between 24 and 48 hours. The elevation of run-on transcriptional activity of FAS gene preceded the increase of FAS mRNA in the liver cytosol by 2 hours, and a similar increasing pattern was observed until 12 hours. However, FAS mRNA concentration decreased gradually after 12 hours, while the transcriptional activity remained at a high level until 48 hours. The changes in FAS mRNA content in the cytosol of rat liver were closely related to the transcriptional activity of FAS gene in the early phase of induction, but another regulatory mechanism seems to operate in the decrease of mRNA after 12 hours. PMID- 1292244 TI - Detection of Mycobacterium tuberculosis in clinical samples from patients with tuberculosis or other pulmonary diseases by polymerase chain reaction. AB - Polymerase chain reaction (PCR) using primers targeting the IS6110 repetitive sequence was employed to detect Mycobacterium tuberculosis in 228 samples from patients with tuberculosis or other pulmonary diseases and controls, and the results were compared with culture and clinical findings. None of culture negative samples from 17 healthy controls were PCR positive. Of 109 active tuberculosis patients under chemotherapy, 88 (80.7%) were PCR positive and were significantly higher than 63 (57.8%) positive by culture. Fifty-nine (93.7) of 63 culture positive and 29 (63.0%) of 46 culture negative specimens contained M. tuberculosis detectable by PCR. In 41 specimens from inactive tuberculosis patients who visited to the chest clinic because of chest problems, 16 (39.0%) also gave PCR positive results. In addition, 14 (46.7%) of 30 specimens submitted for M. tuberculosis culture from patients with pulmonary diseases were PCR positive. Presumptive diagnosis of these PCR positive patients was bronchitis, pneumonia, bronchial asthma, etc. Therefore, this study suggests that PCR is sensitive and specific in detecting M. tuberculosis in clinical specimens. However, the interpretation of the PCR results in specimens from patients with pulmonary diseases should be done cautiously in areas with a high prevalence of tuberculosis. PMID- 1292245 TI - Amelioration of diabetic microalbuminuria and lipid peroxidation by captopril. AB - Administration of captopril, a scavenger of oxygen derived radicals as well as an inhibitor of angiotensin converting enzyme, has been an efficient way of treating diabetic proteinuria. In the present study, we evaluate whether captopril can ameliorate diabetic proteinuria as an effect on oxidative stress in streptozotocin- induced diabetic rats (STZR). At four weeks after the injection of streptozotocin (50 mg/kg, i.v.), STZR (n = 5) exhibited microalbuminuria. The rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.6 +/- 0.3 mg/24hr in age matched control rats (CR; n = 5) and STZR, respectively. Compared to CR, STZR also showed an extremely increased rate of urinary lipid peroxides (LPO) excretion, an index of oxygen derived radicals generation. The respective values for CR and STZR were 0.6 +/- 0.3 and 6.9 +/- 0.6 mumol/24 hr. Significant amelioration of urinary albumin and LPO excretion rate by the treatment of insulin (2 U/day) suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct effect of streptozotocin. Chronic administration of captopril, which did not cause any discernible effect on CR, significantly reduced the urinary albumin excretion rate and decreased LPO excretion in STZR. The urinary albumin excretion rate was significantly correlated with the LPO excretion rate (p = 0.0004). These results suggest that oxidative stress can be responsible for diabetic microalbuminuria, and captopril could diminish the lipid peroxidation and ameliorate the microalbuminuria in diabetic rats. PMID- 1292246 TI - Umbilical vs peripheral vein catheterization for parenteral nutrition in sick premature neonates. AB - The efficacy and safety of using umbilical venous catheters vs. peripheral venous catheters for the delivery of parenteral nutrition was studied in 129 critically ill premature infants who were treated in a neonatal intensive care unit for the first 3 weeks of life. Infants who received parenteral nutrition by umbilical venous catheter had greater parenteral caloric intake, lower physiologic weight loss and greater weight gain during the study as compared to infants who received parenteral nutrition by peripheral vein. While the overall incidence of sepsis was comparable in both groups (19% vs 19.7%), benign and transient episodes of hyperglycemia were seen more commonly in infants receiving parenteral nutrition by umbilical catheters. None of the hyperglycemic infants, however, required insulin therapy. The incidence of other metabolic complication was comparable in both groups. At follow up, no evidence of portal hypertension was detected in any of the infants up to 66 months of age treated with umbilical venous catheters. We conclude that the use of umbilical venous catheter allows for a comparably safe and a more appropriate parenteral nutrition support than peripheral catheters in critically ill premature neonates. PMID- 1292247 TI - Effect of captopril on heavy proteinuria in patients with various glomerular diseases. AB - The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p < 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p < 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven. PMID- 1292248 TI - Expressions of c-fos and c-myc genes during 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)-induced rat hepatocarcinoma. AB - We investigated the expression of the growth-related nuclear proto-oncogenes, c fos and c-myc, in early preneoplastic regions and tumor nodules of 3'-MeDAB induced rat hepatocarcinoma. To amplify the levels of these transcripts, we gave cycloheximide (100 mg/kg B.W. i.p.) to each group of rats. The elevated levels of the 2.2 kb c-fos and 2.4 kb c-myc transcripts appeared as early as the 2nd week after feeding on the 3'-MeDAB diet and lasted through the 4th; 6th weeks and tumor. Southern blot analysis indicated that gross amplification or rearrangements were not observed in DNA of the preneoplastic livers and hepatoma nodules. We also measured the rate of the incorporation of [3H] thymidine into hepatic DNA in order to monitor the rate of cell proliferation occurring at the early preneoplastic periods. We have found that the rate of [3H] thymidine incorporation corresponds to the elevated levels of c-fos and c-myc transcripts in the precancerous stages. This finding suggests that the elevated expressions of c-fos and c-myc may result from the continuous cell proliferative stimuli generated in the carcinogen altered cells, which is essential to the initiation and promotion of chemical hepatocarcinogenesis. PMID- 1292249 TI - DNA flow cytometry in pheochromocytoma and paraganglioma. AB - Flow cytometric DNA analysis was performed on 19 adrenal pheochromocytomas and 6 extra-adrenal paragangliomas in parallel with clinical and histopathological review to determine the usefulness of this technique to predict biologic behavior of these tumors. In pheochromocytomas and paragangliomas, tetraploidy or near tetraploidy occurred in 32% and 33% and aneuploidy in 10% and none respectively. A case of malignant pheochromocytoma had diploid DNA content. Occurrence of aneuploidy or tetraploidy is frequent in clinically benign tumors in conjunction with a marked degree of nuclear atypia and cannot be a predictor of malignancy. PMID- 1292250 TI - Influence of primary tumor site on host anti-tumor immunity. AB - Stage IV-S neuroblastoma, characterized by a primary tumor plus disseminated tumors in liver, skin and bone marrow, has a favorable clinical prognosis when compared to metastatic Stage IV neuroblastoma. This favorable outcome also characterized mice receiving tumor transplants to these "IV-S" sites. We report the testing of the hypothesis that enhanced anti-tumor immunity in "IV-S" site neuroblastoma recipients explains this improved survival. A million murine C1300 neuroblastoma cells were inoculated into 256 A/J mice to either "IV-S" sites of skin, liver, peritoneal cavity, or to the disseminated stage "IV" sites of subcutaneous tissue, muscle, kidney and lung. After 21 and 28 days of tumor growth, spleen cells from tumor bearing mice were harvested and analyzed by a 51 Cr release lymphocytotoxicity assay. Cytotoxic T cell activity was consistently higher at day 28 than day 21. In the liver and in the peritoneal cavity, cytotoxic T cell activity was higher than in other organs, and at day 28 these values were significantly higher than Stage "IV" sites. On the other hand, skin is not a immunologically privileged site in vivo study. PMID- 1292251 TI - Partial mastectomy with axillary lymph node dissection and radiotherapy as a new treatment modality of breast cancer (I). AB - This is the first preliminary report among two consecutive papers. Partial mastectomy(PM), axillary lymph node dissection(AD) and radiotherapy (RT) were performed on seventeen operable breast cancer patients who had been admitted from April 1991 to March 1992 to the department of surgery, Yongdong Severance Hospital for improved cosmetic appearance and better survival rate. Of seventeen patients, 47% were T1 lesion and 76% were stage I and II. Extensive intraductal component(EIC) within or around the tumor was also analyzed. Twenty nine per cent of the patients were EIC positive. The mean number of axillary lymph nodes was 21.5 after PM with AD and 20.5 after mastectomy. For radiotherapy, 4,500 rad was delivered to the breast parenchyma and 1,600 rad of boost to the primary tumor site using the electron beam method after surgery. All patients have since been living well without any local recurrence and were satisfied with breast preservation for the one-year follow-up period. We concluded that the PM, AD and RT can be another surgical treatment modality of breast cancer. A longer follow up data will be followed on the second paper. PMID- 1292252 TI - Multiple basal cell carcinoma associated with keratoacanthoma. AB - We report a case of multiple basal cell carcinoma associated with keratoacanthoma. A 65-year-old Korean female had suffered from multiple, variable sized papules and nodules on the face for 20 years previous to treatment. She had no history of arsenic intake, irradiation, herb medication, or hereditable or preexisting dermatoses. Histopathologically, the tumors revealed typical findings of solid and adenoid types of basal cell carcinoma and keratoacanthoma. PMID- 1292253 TI - A case of anaphylaxis by ant (Ectomomyrmex spp.) venom and measurements of specific IgE and IgG subclasses. AB - Hypersensitivity to the stings of the Hymenoptera has been described since antiquity. The hypersensitive reactions to insect stings vary from minor skin reactions to severe and sometimes fatal anaphylaxis. Concerns about sting hypersensitivity have been increasing because of many incidents of allergic reactions of patients to the fire ant in the southern area of the United States as well as the harvester ant in some areas. We experienced one unique case with severe allergic reactions by ant of the Ectomomyrmex spp. of the subfamily Ponerinae, which is not a harvester ant. For three years the patient had been suffering from generalized allergic reactions such as anaphylaxis after the ant stings four-five attacks in a year. We determined that her reactions were due to specific IgE mediated type I hypersensitivity by the detection of a high level of specific IgE to the ant venom in her serum. The high level of specific IgG4 to the ant venom was also noted in her serum, however, the role of ant venom IgG4 was not clearly determined. PMID- 1292254 TI - Simultaneous repair and rebase of a removable partial denture. AB - A patient presented a unique dental problem: the evulsion of mandibular canines, and the restoration of anterior alveolar bone associated with periodontal disease. A mandibular removable partial denture, bilaterally supported by the canines, premolars, and molar abutments of blade implants, had been worn for more than ten years. The open clasps in the canine areas were irritating the oral tissues, and the space under the anterior saddle of the denture was retaining food. Both situations needed immediate consideration. The evulsed canines were reproduced in autocured acrylic and secured in the clasps of the denture. The space under the saddle was rebased with autocured acrylic. Since both areas were adjacent to each other, they were splinted together simultaneously. The patient was satisfied with having the old denture repaired without being deprived of the prosthesis for an extended period of time. PMID- 1292255 TI - Smokeless tobacco. PMID- 1292256 TI - OSHA regulations relating to bloodborne diseases. PMID- 1292257 TI - What you should be doing about the American with Disabilities Act. PMID- 1292259 TI - [It is important that all members take part in the discussions. Interview by Jan Thomasson]. PMID- 1292260 TI - [New regulations hit hard against women. Number of approved occupational injuries halved. Interview by Elisabet Forslind]. PMID- 1292258 TI - Orofacial injury relative to sporting activity ... How can interested members of the Virginia Dental Association become Involved? PMID- 1292261 TI - [More than 500 could lose jobs in occupational health services]. PMID- 1292262 TI - [Changes occur altogether too fast. Interview by Jan Thomasson]. PMID- 1292263 TI - [Storm over Malmo's effect on health care. Interview by Kaj Nyman]. PMID- 1292264 TI - [Anniversary celebrant chooses new spokesperson]. PMID- 1292265 TI - [Difficult everyday life casts a shadow over the future]. PMID- 1292266 TI - [Nurses may be going their own way]. PMID- 1292267 TI - [Senile dementia and nursing care in a university course]. PMID- 1292268 TI - [Hygiene nurses stop bacterias' spread. Interview by Maria Ejd]. PMID- 1292269 TI - [Inadequate hygiene costs Swedish health care half a billion per year. Interview by Maria Ejd]. PMID- 1292270 TI - [New proposal for wage policy program. Now you can have an effect on your salary]. PMID- 1292271 TI - [Do professional organizations have a future?]. PMID- 1292272 TI - [Organizations' needs even in the future. Interview by Jan Thomasson]. PMID- 1292273 TI - [Ethnic nurse gives Swedish instruction in nursing care]. PMID- 1292274 TI - [Job in Finland provides experience and hard cash]. PMID- 1292275 TI - [Norway, Falun, Oregon--3 places to prioritize in health care]. PMID- 1292276 TI - [Dear politicians!]. PMID- 1292278 TI - [Fight unemployment!]. PMID- 1292277 TI - [Hungarian nurse on a visit to Scania. Swedish experiences give support in professional work]. PMID- 1292279 TI - [Nearness to patients gives pleasure in work]. PMID- 1292280 TI - [A tool to improve quality of care. Interview by Maria Ejd]. PMID- 1292281 TI - [The new General Director of the Public Health Institute: SHSTF's members have a key role in public health activities. Interview by Jan Thomasson]. PMID- 1292282 TI - [Health care in the USA. Insurance is expensive--Rita takes a chance on never needing hospital care. Interview by Asa Jonholt]. PMID- 1292283 TI - [Health care in the USA. Private hospital run just like any business]. PMID- 1292284 TI - [Health care in the USA. Lawyers get wealthy on physicians' mistakes. Interview by Jonas Hallen]. PMID- 1292285 TI - [Paradise knocks holes in our condemnation of mentally handicapped]. PMID- 1292286 TI - [Right to Work analyzed: more power to employers, less to the profession. Interview by Jan Thomasson]. PMID- 1292287 TI - [Whose interest weighs heaviest?]. PMID- 1292288 TI - [She makes the best of a necessary evil. Barbro praised for care in Gula Villan]. PMID- 1292289 TI - [Wage differences increase--a long way to go to equal pay for equal work ]. PMID- 1292291 TI - [Lena has studied women's work environment. Nursing profession is a good one to grow old in. Interview by Britta Collberg]. PMID- 1292290 TI - [New data system for primary health care. Medea is district nurses' upper hand]. PMID- 1292293 TI - [Do not destroy the right to work]. PMID- 1292292 TI - [From antiquity to the 1900s. History of medicine has been collected in Lund]. PMID- 1292294 TI - [Safe routines protect Catherine's life]. PMID- 1292295 TI - [We must prevent accidents not look for scapegoats. Interview by Maria Ejd]. PMID- 1292296 TI - [Employment agencies help the USA recruit Swedish nurses]. PMID- 1292297 TI - [The cytoarchitectonics of the adenohypophysis in light of the concepts of cellular flows]. AB - Analysis of published data allows to suggest a possible model of adenohypophyseal cytoarchitectonics based on the concepts of tissue self-renewal and streaming in this gland. The model provides a framework for understanding: a) the existence of ambiguous cellular elements; b) change of relationship between different types of hormone secreting cells with sex-dependent prevalence of somato- or lactotrophs; c) relatively high proliferative activity of lactotrophs in mature pituitary gland; d) specific spatial arrangement of various types of hormone secreting cells; e) multiple effects of some bioregulators on the secretion of two or more pituitary hormones; f) the existence of polyfunctional pituitary adenomata containing and secreting several adenohypophyseal hormones simultaneously. Possible approaches to thorough evaluation and testing of the model in experiments using organ or cell cultures of adenohypophysis are discussed. PMID- 1292298 TI - [Structures in neurosurgery in Germany 1991. Part I. Presented by the Structure Commission of the German Society of Neurosurgery]. PMID- 1292299 TI - Classification and coding in neurosurgery. AB - Twelve years' experience in classification and coding by a neurosurgical department serving a population of about 1.5 million is presented. The involvement of clinicians and the relationship to health service resource management is demonstrated. The incorporation of a comprehensive coding system (the READ codes) is outlined. PMID- 1292300 TI - [Quality assurance--an important factor in the structure of medical management of the future]. AB - Quality of medical practice has several prerequisites. A certain structural quality is essential to ensure good quality medical performance. Structural and performance quality both lead to result quality. Performance quality is dependent on well-working structures. With respect to neurosurgery a high level hospital organisation is required which allows equally qualified medical performance. Structure therefore has to attain a standard to stand up to quality assurance criteria. Next to hospital equipment structural quality requires sufficient staff capacity as well as unlimited neurosurgical access to technical equipment such as computerized tomography, MR, angiography and also intensive care under neurosurgical supervision. Quality assurance has been widely discussed in recent years. Measures to guarantee quality assurance, as required by federal law in Germany, are taking three different steps, first a model phase as a scientific study developing methods and observation, a second phase called study phase with wide effects and institution in various departments. In this phase the effectiveness of the procedure is tested and assured. In the third phase routine use is instituted. In quality assurance in neurosurgery phase two is presently tested, phase three is in preparation. PMID- 1292301 TI - [Evaluation of economic business management in the hospital. Results from four neurosurgical clinics]. AB - An audit of economicalness performed by one company from 1980 to 1985 in four neurosurgical departments is presented. The report is restricted to medical care. There is a considerable difference in findings: in the department first looked at there are 3.8 patients per surgeon and in the 1985 examination 5.4. These departments being well comparable otherwise both judgement and competence of the business consultants involved must be questioned. PMID- 1292302 TI - [43d Annual Meeting of the German Society of Neurosurgery 10-13 May 1992 in Frankfurt. Financing problems of the hospital]. PMID- 1292303 TI - [Structural problems and future perspectives of hospital specialty departments, especially in neurosurgery]. PMID- 1292304 TI - Alpha thalassaemia in Saudis. AB - The alpha-thalassaemias are group of inherited anaemias. Their severity is known to increase with the number of alpha-globin genes deleted. Employing different types of restriction enzymes, we found that alpha-thalassaemia-2 are more common than held previously. On the basis of our results we also anticipate that the haplotype alpha alpha alpha anti3.7/ occurs at a higher frequency. PMID- 1292305 TI - Hydroxyurea for the treatment of sickle cell disease. AB - In this study 21 adults with severe form of sickle cell disease (SCD; sickle cell anaemia, n = 15; Hb S/beta degree-thal, n = 6) were treated with hydroxyurea (HU) to assess the effectiveness of the drug in managing SCD. The individual dose was selected for each patient. The dose selection was based on the HU clearance study. Thereafter, the patients received daily doses of 15-20 mg/kg body weight. An evaluation data form was filled out at the monthly visit. The severity index (SI) of the disease was determined and haematological parameters including red cell indices, platelet counts, reticulocyte counts, irreversibly sickled cells, red cell deformability, Hb F, Hb F cells, total and direct bilirubin levels were measured prior to treatment, at follow-up intervals during treatment and after cessation of treatment. The trial period lasted 3 months. Statistically significant improvement was observed in the clinical presentation, haematological and biochemical parameters. Hb F level and F cells showed a significant increase in most patients, but to a variable degree. A major resultant effect was an increase in mean cell volume. Our experience shows that HU can be used for the treatment of severe forms of SCD with no major side effects, provided that the doses are monitored and that laboratory investigations are regularly undertaken. PMID- 1292306 TI - Neutralization and immunoaffinity chromatography of erythroid colony-stimulating activity in mouse plasma by an anti-erythropoietin monoclonal antibody. AB - A relationship between erythropoietin (EPO) and erythroid colony-stimulating activity (ECSA) in mouse plasma was examined in fetal mouse liver cell (FMLC) cultures using a monoclonal antibody (MoAb) R2 raised against recombinant human EPO. Most of the ECSA in plasma from normal, anemic, and hypoxic mice was neutralized by MoAb. This neutralization could be reversed by addition of excess of anemic plasma or by preincubation of MoAb with goat anti-mouse IgG antibody. Most of the plasma ECSA was bound to an immunoadsorbent column containing the immobilized MoAb, and the retained ECSA was completely neutralized by MoAb. The plasma ECSA and standard EPO showed parallel dose-response curves and additive effect on CFU-E stimulation. Based on these findings, we conclude that mouse plasma ECSA detected by CFU-E assay using FMLCs is mainly due to EPO. PMID- 1292307 TI - Serum selenium status in children with iron deficiency anemia. AB - Serum selenium concentration was investigated in 40 children with iron deficiency anemia and in 40 control subjects matched for age, sex and geographical origin. A spectrofluorometric method was used for determination of the selenium level. It was found to be significantly lower (p < 0.001) in the patient group, which consisted of both normally developed and malnourished children. Patients also having pica had higher levels of selenium compared to patients without pica. There was no relation between the serum selenium concentration and hematological parameters such as hemoglobin, serum iron, serum iron binding capacity and unsaturated iron binding capacity. However the results of 15 patients followed during iron therapy indicated that the duration of the anemic period may affect the selenium concentration. This study also suggests the effectiveness of iron and selenium administration. PMID- 1292308 TI - Severe congenital dysfibrinogenemia (fibrinogen-Riyadh): a family study. AB - Congenital severe dysfibrinogenemia was discovered in a small Saudi family. Their single child exhibited abnormal severe bleeding tendency since birth and his coagulation profile revealed evidence of severe dysfibrinogenemia. The parents who were first-degree cousins and completely asymptomatic showed evidence of dysfibrinogenemia but to lesser degree than in their son. The child presented with large cephalohematoma and evidence of intracranial hemorrhage and left hemiparesis. He was treated with cryoprecipitate and his hematoma resolved, but his neurological deficit remained. PMID- 1292309 TI - Long-term survival of a baby with homozygous alpha-thalassemia-1. AB - Triplets born to a Chinese woman consisted of 2 healthy boys and a girl with hemoglobin Bart's hydrops syndrome. The girl with hemoglobin Bart's hydrops syndrome, confirmed by gene analysis to be homozygous for alpha-thalassemia-1, survives for 27 months at the time of reporting. The dilemma in sustaining her life and the availability of other therapeutic options are briefly discussed. This is the third case report of homozygous alpha-thalassemia-1 with long-term survival. PMID- 1292310 TI - Cytogenetic evidence for extramedullary blast crisis with t(8;13)(q11;p11) in chronic myelomonocytic leukemia. AB - A 27-year-old male developed massive generalized lymphadenopathy with chronic myelomonocytic leukemia (CMML) presenting as extramedullary blast crisis mimicking a lymphocytic lymphoma. On presentation, a consistent chromosomal abnormality involving chromosomes 8 and 13, i.e. 46,XY,t(8;13) (q11;p11), was present in lymph node tissue, bone marrow and unstimulated peripheral blood. The appearance of trisomy 21 in addition to the presence of the original cytogenetic abnormality is simply regarded as clonal evolution, i.e. 47,XY,t(8;13)(q11;p11),+21. The importance of the cytogenetics lies in finding the same abnormality in bone marrow and lymph node, adding evidence that the immunologically similar cells in the two sites have arisen from a common progenitor cell. To our knowledge, this novel chromosomal abnormality has not been reported in association with a unique case. PMID- 1292311 TI - Isolated cerebellar infarction as a presenting symptom of polycythemia vera. AB - Although polycythemia vera is one of the reported causes for cerebral infarction, isolated cerebellar infarction, a rare disorder, was never reported in combination with polycythemia vera. This is a report of a 72-year-old woman in whom isolated cerebellar infarction was the presenting manifestation of polycythemia vera. The patient was treated with recurrent phlebotomies until the hematocrit decreased to < 45%. This treatment was followed by marked neurological improvement. A better awareness of the possibility of cerebellar infarction in polycythemia vera may disclose additional cases. PMID- 1292312 TI - Adult T cell leukemia associated with eosinophilia: analysis of eosinophil stimulating factors produced by leukemic cells. AB - The mechanism of eosinophilia in a patient with adult T cell leukemia (ATL) was investigated. A 61-year-old woman with ATL presented marked eosinophilia. No parasite infections or allergic diseases were found in this patient. The number of eosinophils fluctuated in parallel with that of ATL cells during her clinical course. The patient's serum and the culture supernatant of ATL cells showed eosinophil colony-stimulating activity. Northern blot analysis of granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5), which are known eosinophil CSFs, showed that only GM-CSF but not IL-3 or IL-5 was expressed in freshly separated and cultured ATL cells. Since neutrophil and monocyte numbers did not increase, it is suggested that GM CSF and unknown cytokines other than IL-3 and IL-5 produced by ATL cells synergistically stimulated eosinophil precursors in the present case. PMID- 1292313 TI - Primary adrenal lymphoma. PMID- 1292314 TI - The bcr breakpoint and chronic phase duration in chronic myeloid leukemia. PMID- 1292315 TI - Thrombocytopenia in the newborn. PMID- 1292316 TI - A simple technique to instantly convert from insufflation to positive pressure ventilation. PMID- 1292318 TI - The standard of care. PMID- 1292317 TI - HCFA medicare billing update. PMID- 1292319 TI - Factors which predict performance on the National Certification Examination for Nurse Anesthetists. AB - Predicting the performance of registered nurse anesthesia students (RNAS) on the national certification examination (NCE) is an area of interest to educators, students, and employers. Following graduation from an accredited nurse anesthesia educational program, RNAS must pass the NCE to practice. The purpose of this study was to investigate 13 academic, demographic, and preadmission factors which predict RNAS' performance on the NCE. This retrospective analysis included 1,690 RNAS who took the five NCEs administered from December 1987 through December 1989. Results of multiple regression analyses revealed that seven of the 13 academic, demographic, and preadmission variables were predictive of performance on the NCE. These variables included science and overall grade point average (GPA), highest degree attained before entry, gender, number of cases, age, and years of nursing experience. The GPA in science accounted for 24% of the variance in the overall certification examination score, and the remaining six variables contributed an additional 3% to the variance. Variables which were not predictive of performance on the NCE included type of nursing preparation, clinical background, type of nurse anesthesia program, case hours, number of science hours, and length of the nurse anesthesia program. Additional research findings from the one-way analysis of variance of the categorical variables indicate that level of education before entry into a nurse anesthesia educational program is predictive of performance on the NCE. RNAS with bachelor's or master's degrees achieve higher mean certification examination scores than RNAS with diplomas or associate degrees. Similar results were found for the type of nurse anesthesia program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292320 TI - Hearing loss after general anesthesia for cecectomy and small bowel resection. AB - Acute hearing deficit following nonotologic surgery and general anesthesia is a rare phenomenon. Hearing loss following anesthesia has more commonly been associated with spinal anesthesia or following cardiopulmonary bypass surgical procedures. This case study describes a patient who developed a left-sided hearing loss after cecectomy and small bowel resection. The postoperative management was directed toward reversing idiopathic hearing loss secondary to a microvascular hypoperfusion etiology. Possible causative factors and the management of sensorineural hearing loss following anesthesia are discussed. PMID- 1292321 TI - Admissions issues and disabilities law. PMID- 1292322 TI - Effective methods of in-line intravenous fluid warming at low to moderate infusion rates. AB - Three methods of warming intravenous (IV) fluids were examined. An in-line blood warmer was generally ineffective at flow rates of < 250 mL/hr but did produce temperatures of 30 to 31 degrees C at the catheter when the infusion rate was 500 to 1,000 mL/hr and the tubing was insulated. An in-line hot water bath produced temperatures of > or = 30 degrees C at flow rates of 200 to 1,000 mL/hr with uninsulated tubing. The addition of insulation maintained on infusate temperature of > or = 30 degrees C at a rate of 100 mL/hr. Application of a K-Thermia pad to the IV tubing close to the patient maintained an infusate temperature of > or = 30 degrees C at rates of 50 to 200 mL/hr. Warming at rates of 200 to 1,000 mL/hr is most effective with an in-line hot water bath. Warming at low infusion rates is best accomplished with a K-Thermia pad. The use of in-line blood warmers for routine fluid warming is ineffective. PMID- 1292324 TI - Council on Accreditation of Nurse Anesthesia Educational Programs. PMID- 1292323 TI - AANA journal course: update for nurse anesthetists--blood-brain barrier function alteration during anesthesia. AB - With some exceptions, the entire central nervous system (CNS) is encircled by the blood-brain barrier (BBB). The function of the BBB is to sustain the CNS in a homeostatic environment. A variety of occurrences during an anesthetic have been shown to disrupt the BBB. Alterations of electrolytes or drugs in the systemic circulation at the time of a disruption in the BBB could result in an abnormal concentration of these molecules in the CNS leading to abnormal CNS neuronal transmissions which may manifest as both intraoperative or postoperative problems. PMID- 1292326 TI - Assessment of a self-designed protocol on patients with adverse reactions to beta lactam antibiotics. AB - Suspected adverse reactions to beta-lactam antibiotics are the most frequent reason for consultation in relation WMH drug allergy. Because of their therapeutical usefulness and wide use, we developed a protocol for confirmation or exclusion of this type of allergy. The proposed protocol is based on clinical, causal and laboratory criteria that are used to assign scores from 0 to 9 points. Patients with scores between 0 and 3 are considered to be highly prone to beta lactam antibiotic allergy and are given an alternative therapy that is selected by applying skin provocation tests (SPT). Those with a score of 9 points are excluded. Finally, those with scores between 4 and 8 are subjected to skin tests with 5 antigens (penicillin G, ampicillin, cephalothin, Penkit PPL and Penkit MDM); if they give negative results they are subsequently subjected to oral provocation with beta-lactam antibiotics. In this work we report the results obtained from 150 patients analysed for 28 variables altogether. The results allowed us to rule out adverse reactions in 94 patients. Only 9 individuals yielded positive skin tests, and only one gave a positive oral provocation (bronchospasm, 6 hours after subjection to the test). The usefulness of the proposed protocol, the profitability of the test applied and the mechanisms involved are assessed. PMID- 1292325 TI - A multi-allergen ELISA screening method. Comparison with Pharmacia CAP system and Phazet skin prick test. AB - Eighty consecutive subjects, coming to our service as suffering from conjunctivitis and/or rhinitis and/or asthma, were investigated by a new multi allergen enzymatic screening immunoassay (Profilo, Bio-Allergy, Rome, Italy) regarding to serum specific IgE for groups of inhalant allergens (Dermatophagoides, Parietaria, grasses, trees, animal danders). These groups include allergens which are most frequently responsible of allergy in our country. Indices of diagnostic accuracy of this assay were analyzed in relation to skin prick test (SPT, Phazet, Pharmacia), as in vivo reference test, and Pharmacia CAP System, as in vitro reference test, comparing the results achieved by these tests in the same group of subjects. Profilo showed high significant (p < 0.0005) correlations and satisfactory indices of diagnostic accuracy (sensitivity, specificity, predictive values of positive and negative, and efficiency) for the tested allergens with reference to both Phazet SPT and CAP System. In addition, the method appeared very rapid and simple, so that it could be performed in the physician's office. PMID- 1292327 TI - Comparison between late onset and childhood asthma. AB - BACKGROUND: The onset of asthma frequently occurs after the age of 50 yr and the severity and causes of this late onset disease are poorly known. METHODS: 25 chronic asthmatics (65.7 +/- 6.5 yr) whose asthma started after the age of 50 yr were compared with 23 chronic asthmatic children (11.6 +/- 2.8 yr) and 24 COPD patients (61.6 +/- 3.4 yr). Both asthmatic groups had a similar apparent duration of asthma. None of the asthmatics was a smoker. All COPD were smokers. The severity of asthma was defined according to the Aas score. FVC, FEV1, MMEFR, Raw were tested and reversibility of bronchial obstruction was determined on Raw after salbutamol inhalation. Allergy was assessed by skin prick tests, RAST and total serum IgE (PRIST). RESULTS: Patients with childhood asthma had: 1) a significantly lower clinical severity of asthma; 2) a significantly less severe bronchial obstruction, and 3) a significantly greater reversibility than old age asthmatics. There was no significant difference between pulmonary function tests pre- and post-bronchodilators between COPD and old-age asthmatics. All asthmatic children and 40% of older patients were allergic. CONCLUSIONS: The occurrence of asthma in old age patients leads to a more severe course of the disease and allergy appears to play a role in many old age patients. PMID- 1292328 TI - Allergic skin reactivity in 232 patients over 50 years. AB - We examined two hundred and thirty-two out-patients, ranging in age from 50 to 75 yrs. All patients were submitted to skin-tests: prick and, if it was necessary, intradermal reactions and/or RAST. Allergens employed were Gramineae, Parietaria, Olea, dermatophagoides Farinae, dermatophagoides Pteronyssinus, house dust, cat and dog skin scales. One hundred and twenty-eight subjects had positive responses to one or more aeroallergens. Asthma was the most frequent condition both in skin positives and in skin-negatives. For 58% of skin-positives and 51% of skin negatives the symptoms' onset was more than 10 yrs before our check. In 58.6% of patients we found positive reaction to dermatophagoides Farinae, in 51.5% to house dust, in 47.6% to dermatophagoides Pteronyssinus, in 34.3% to Gramineae, in 28.9% to parietaria and in 14.8% to olea. Fifty-four skin-positives subjects carried out lung function tests; in twenty-eight of them we found a bronchial obstruction. In more than 50% of the subjects, which had shown a reactivity to aeroallergens, we prescribed a specific hyposensitization. These data suggest that skin tests results in elderly patients can have a relevant role in preventive and pharmacological treatment, improving life quality. PMID- 1292330 TI - Plasma kallikrein amidolytic activity in bronchial asthma. AB - We have investigated plasma kallikrein amidolytic activity in the following groups of patients: 1. Normal control group of blood donors. 2. Extrinsic pollen activated bronchial asthma patients, during periods of symptomatology and at a later time after the spring. 3. Subjects with atopic bronchial asthma in acute phase when admitted to our hospital's emergency room and later when clinically recovered. 4. Subjects with extrinsic bronchial asthma, sensitive to Dermatophagoides pteronyssinus and Dermatophagoides farinae with FEV1 < 80%. 5. Subjects with extrinsic bronchial asthma, sensitive to Dermatophagoides pteronissinus and Dermatophagoides farinae in a state of clinical rest. After 9 minutes of activation, the following results were found, with a significance of p < 0.01: There are significant differences between the normal group and those that we consider the active groups, asthma FEV1 < 80%, pollen-sensitive asthma in springtime and acute asthma. No significant differences exist between the normal group and inactive groups, inactive asthma, pollen-sensitive asthma out of springtime and acute asthma inactive. Significant differences exist in active groups (acute asthma and pollen-sensitive asthma in springtime) when they become inactive (acute asthma inactive and pollen-sensitive asthma out of springtime). The active groups have a higher plasma kallikrein amidolytic activity than both the inactive and control groups. PMID- 1292329 TI - Determination of eosinophil rate after nasal provocation test in allergic rhinitis diagnosis. AB - After nasal provocation test in patients with allergic rhinitis, using the allergen they were sensitized to, we have observed: 1) an increase in the percentage of nasal eosinophils after 2, 3, 24 and 48 hours; 2) sneezes, mainly in the first 30 minutes; 3) nasal obstruction in the first three hours; 4) absence of rhinorrhea, but not in all the patients; and 5) no predominance of nasal, auricular and/or palatine pruritus at any time. When patients without rhinitis, or with allergic rhinitis were stimulated using a pneumoallergen they were not sensitized to, no significative increase in the nasal eosinophils percentage was found. No symptoms were observed either. So, we can conclude that nasal secretion samples, for eosinophilia percentage determination, should be taken from 2 to 48 hours after nasal provocation, and that the most frequent symptoms, which are probably related to cellular changes, are nasal obstruction and sneezes. PMID- 1292331 TI - An unusual case of allergy to doxycycline. PMID- 1292333 TI - Things are worse than ever. PMID- 1292334 TI - Practical considerations in the interpretation of urine drug screens. PMID- 1292335 TI - Clinton's playing field. PMID- 1292332 TI - Adolescent pregnancy: a regional tragedy. PMID- 1292336 TI - The UAB School of Medicine. The founders and the almost forgotten essential doctor: Harry Lee Jackson. PMID- 1292337 TI - Mobilization of an intracellular glycoprotein (Mac-1) on monocytes and granulocytes during hemodialysis. AB - We studied the upregulation of the intracellular glycoprotein Mac-1 (CD11b/CD18, CR3) on monocytes and granulocytes during 36 bicarbonate hemodialyses in 12 patients who were randomly treated with Cuprophan (Cu), Hemophan (He) or Polysulfone (PS; low-flux) membranes. The degree of mobilization of this adhesion protein was related to changes in granulocyte and monocyte count, generation of C3a and production of interleukin-1 beta in plasma. Mac-1 expression on granulocytes was significantly higher after 5 and 15 min of Cu hemodialysis as compared to He or PS dialyses (p < 0.001) and correlated to changes in granulocyte count at 15 min (r = 0.62 and r = 0.76, p < 0.001). No differences in early Mac-1 mobilization on circulating monocytes was observed despite a decrease in cell count. Mac-1 expression on monocytes and granulocytes in the venous blood line at 180 min of treatment was significantly higher during Cu dialysis as compared to He and PS dialyses (p < 0.02 and p < 0.001, respectively). Early generation of C3a was higher in patients on Cu dialysis than in He or PS dialysis (p < 0.001) and correlated both to granulocytopenia (r = 0.45, p < 0.01) and to the subsequent increase in Mac-1 expression on granulocytes (r = 0.63, p < 0.001). An early increase in Mac-1 expression on monocytes was accompanied by an increase in plasma interleukin-1 beta later during dialysis (p < 0.05). Studies of Mac-1 expression during hemodialysis increased the sensitivity of biocompatibility measurements and correlated better than complement generation to changes in granulocyte count as it mediates adhesion to endothelial cells. PMID- 1292338 TI - Serum levels of the soluble interleukin-2 receptor are dependent on the kidney function. AB - We have investigated the influence of kidney function on soluble interleukin-2 receptor (S-IL-2R) serum levels. S-IL-2R is a glycoprotein with a molecular weight of 45 kDa. The serum concentration of S-IL-2R was positively correlated to serum creatinine (r = 0.35) and complement factor D (r = 0.30), a low molecular weight protein, and the reciprocal value of S-IL-2R was negatively correlated to 51Cr-EDTA clearance (r = -0.35). When measuring S-IL-2R and factor D in a wide range of serum creatinine (140-1,380 mumol/l), a high positive correlation was found between factor D and serum creatinine. S-IL-2R and serum creatinine had r = 0.92 and r = 0.79, p = 0.0001, respectively. The correlation coefficient between factor D and S-IL-2R was 0.86. S-IL-2R is used as a marker for an increased activity of the immune system and in a variety of lymphoproliferative disorders. However, it is important to keep in mind that a reduced kidney function may contribute to the increased S-IL-2R levels seen in different immune diseases. Therefore, renal function should be taken into account in the interpretation of elevated plasma concentrations of S-IL-2R. PMID- 1292339 TI - Prospective study on captopril renography in hypertensive patients. AB - Six hundred and sixty-seven hypertensive patients were analyzed by captopril enhanced scintigraphy. If time to reach maximal activity (Tmax) was > or = 5 min using 99mTc-diethylenetriaminepentaacetic acid (DTPA) or > or = 3 min with 123I-o iodohippurate (OIH) and 99mTc-mercaptoacetyltriglycine (MAG3) and washout time > or = 15 min, a control study with nifedipine was performed. If the difference between Tmax under captopril and nifedipine premedication was > or = 5 min with 99mTc-DTPA or > or = 3 min with 123I-OIH and 99mTc-MAG3, the renogram was defined highly suggestive of renovascular hypertension. In the evaluation of bilateral abnormalities an additional parameter was considered, i.e. the presence of functional asymmetry of the emuntories susceptible of partial reversal in the control study under nifedipine. Based on these criteria, 58 out of 667 (8.7%) scintigrams were found to be abnormal. Thirty-five of these 58 patients and 32 of the remaining 609 scintigraphically negative cases underwent additional arteriographic examination. A renal vascular stenosis > or = 50% was found in 33 out of 35 (94.2%) patients with positive scintigraphy and in 3 out of 32 patients with negative scintigraphy. By examining results of the 67 patients undergoing arteriography, the sensitivity of captopril-enhanced scintigraphy was estimated to be 91.6%, with a specificity of 93.5%, an accuracy of 92.5%, and predictive values of a positive or negative result of 94.2 and 90.6%, respectively. By restricting analysis to bilateral stenosis, sensitivity was found to be 76.9%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292340 TI - Effect of high-flux hemodialysis on quality of life and neuropsychological function in chronic hemodialysis patients. AB - The objective was to evaluate the effect of high-flux hemodialysis on quality of life, intra- and interdialytic symptoms and neuropsychological function. The study was double-blind single cross-over with random allocation to order of treatment. The patients were stable adult hospital hemodialysis patients. Both the conventional and high-flux membranes were cellulose acetate, the dialysate was bicarbonate, and dialysate sodium was held constant. The high-flux membrane had an ultrafiltration rate of 15 ml/h/mm Hg transmembrane pressure, a B12 clearance of 88 ml/min and a beta 2-microglobulin clearance of 11.4 ml/min. The values of the conventional membrane were 3.5-5.0, 34-45 and negligible. Each treatment period was 4 months. Twenty-two patients completed both phases of the cross-over. The KT/V value was higher during high-flux than conventional treatment; 1.42 versus 1.27(p < 0.05). There were no differences between high flux and conventional treatment with respect to quality of life. Symptoms during dialysis were less severe during high-flux than conventional treatment for 12/14 items. Only 3 items reached statistical significance (0.05 > p > 0.01) and none were clinically significant. Symptoms between dialyses were less severe during high-flux than conventional treatment for 18/20 items. No single item had a statistically significant improvement but 3 had clinically important improvement. Among the 23 neuropsychological variables, none demonstrated statistically significant changes. PMID- 1292341 TI - Bisphosphonate kinetics in patients undergoing continuous ambulatory peritoneal dialysis: relations to dynamic bone histomorphometry, osteocalcin and parathyroid hormone. AB - In the evaluation of renal osteodystrophy bone biopsy is often performed. However, a reliable noninvasive test could be very useful, and recently the estimation of osseous tracer uptake as an index of bone formation has been introduced-the bone bisphosphonate clearance (BBC). The aim of the present investigation therefore was to compare BBC with parameters of bone histology, serum levels of osteocalcin, alkaline phosphatase, and parathyroid hormone in patients (n = 8) undergoing continuous ambulatory peritoneal dialysis (CAPD). No significant correlations were found between BBC values and the bone histomorphometrical variables measured. A positive correlation was seen between serum osteocalcin and resorption and active resorption surface (p < 0.05), as well as tetracycline-labelled surface, bone formation rate, surfaces, volume and tissue referents, respectively (p < 0.01). Furthermore, levels of alkaline phosphatase showed significant correlations to mineral appositional rate, tetracycline-labelled surface and bone formation rate, volume referent (p < 0.05). Values of parathyroid hormone were significantly correlated to resorption surface (p < 0.02), active resorption surface, mineral appositional rate and mineralization lag time (p < 0.05). In conclusion, BBC was of no use in patients treated with CAPD as a noninvasive test for evaluation of bone histomorphometry. However, osteocalcin correlated best with resorption and bone dynamics indices. Levels of alkaline phosphatase and parathyroid hormone were of a more limited value. PMID- 1292342 TI - Effects of naloxone infusion in patients with septic shock and renal failure: a limited experience. AB - Septic shock is frequently associated with acute renal failure. Management of these patients becomes complicated if either the renal or systemic hemodynamic derangement cannot be corrected. Although previously large doses of furosemide and naloxone infusion have been used separately in managing these patients, the combination of both agents has not been employed. We therefore report our limited experience with this combined treatment in 5 patients with septic shock, of which 4 had acute renal failure. PMID- 1292343 TI - Glomerular morphometry of adriamycin-induced focal and segmental glomerulosclerosis in the rat. AB - The present paper presents a morphometric study of the evolution of the glomerulus in Adriamycin-induced focal and segmental glomerulosclerosis in the rat over 32 weeks. The morphometric parameters studied generally varied significantly when the groups treated with Adriamycin were compared with controls. Glomerular area and perimeter showed an irregular pattern and finally ended up with values similar to those of the control group. Glomerular capillary tuft area and perimeter were always significantly greater in Adriamycin-treated groups than in controls. The mesangial area of treated animals increased over the study period in comparison with that of controls. While the total number of cells in the glomerular capillary tuft had an irregular pattern, the proportion of cells in relation to glomerular capillary tuft area was significantly lower in treated animals than in controls. PMID- 1292344 TI - Pioneer nephrologists of Berlin. PMID- 1292345 TI - Balloon expandable stents to treat central venous stenoses in hemodialysis patients. AB - Vascular access failure in hemodialysis patients remains a significant problem. The use of thrombolytic agents and balloon angioplasty instead of or in conjunction with surgical revision, has been helpful in increasing the life span of vascular access in these patients. The application of newer endovascular therapies, such as vascular stents, may further improve the salvage rate of hemodialysis access sites. These stents may be particularly valuable in treating stenoses in large central veins. We present 2 cases in which a balloon-expandable Palmaz stent was used to treat a central venous stenosis causing signs of vascular access failure. PMID- 1292346 TI - Disappearance of immune deposits with EDTA chelation therapy in a case of IgA nephropathy. AB - In this report, we describe the development of renal function impairment in a 33 year-old patient with mesangial IgA nephropathy and a history of recent gout. Increased body lead burden was identified with a positive EDTA mobilization test. The patient was treated with 1 g of edetate disodium calcium weekly for 2 months until normalization of urinary lead excretion. Improvement of renal function and proteinuria were noted. It was even more interesting to find that both immunofluorescence and electron microscopy studies of the second biopsy specimen revealed the loss of previous mesangial immune deposits. Our case demonstrated that lead may be a nonspecifically damaging factor related to the deterioration of renal function in patients with preexisting renal disease. Moreover, the disappearance of mesangial immune deposits after chelation therapy has not been previously documented. The pathogenetic basis of this observation is unknown, and its causal relationship with lead requires further elucidation. PMID- 1292347 TI - Chronic hypovolemia associated with accelerated hypertension and orthostatic hypotension in a patient on continuous ambulatory peritoneal dialysis. AB - We report a patient with nondiabetic end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD) associated with chronic hypovolemia. Despite the administration of nilvadipine, the patient showed accelerated hypertension and concomitantly orthostatic hypotension. Plasma renin activity was markedly high, and blockade of angiotensin II action by captopril or an angiotension II antagonist decreased the supine blood pressure. This indicated that the enhanced activity of the renin-angiotensin system was the principal cause of the supine hypertension. The plasma concentration of norepinephrine was also very high. After correction of hypovolemia by blood transfusion, the enhancement of the renin-angiotensin system and high plasma norepinephrine level were reduced, and symptomatic orthostatic hypotension disappeared. The accelerated hypertension was easily controlled by the administration of low-dose captopril and nilvadipine. These findings suggest that chronic hypovolemia related to the intractable supine hypertension as well as orthostatic hypotension. Hypovolemia-induced enhancement of the renin-angiotensin system and sympathetic nerve activity may cause vasoconstrictive hypertension in patients on CAPD. PMID- 1292348 TI - Membranoproliferative glomerulonephritis associated with multicentric angiofollicular lymph node hyperplasia. Case report and review of the literature. AB - A 14-year-old boy presented with fever, anemia, hepatosplenomegaly, generalized lymphadenopathy and nephrotic syndrome. Lymph node biopsy showed angiofollicular lymph node hyperplasia (generalized Castleman's disease) of the plasma cell type. Kidney biopsy showed membranoproliferative glomerulonephritis type 1. Complete remission was achieved with corticosteroid treatment and repeat kidney biopsy 22 months later showed complete resolution of the renal pathology. The association between membranoproliferative glomerulonephritis and multicentric angiofollicular lymph node hyperplasia, plasma cell type, has not previously been reported. PMID- 1292349 TI - Effect of recombinant human growth hormone in a postpediatric hemodialysis patient with delayed growth. AB - We present an 18-year-old patient who has been on renal replacement therapy since the age of 11. He had growth retardation and delayed puberty, with a bone age of 13.6 years. Treatment with human recombinant growth hormone (rhGH) resulted in a clearcut increase in height and lean body mass. We emphasize that rhGH treatment could be tried even at a postpediatric age, provided bone radiology suggests that further growth is possible. PMID- 1292350 TI - Influence of anaesthesia on renal hippurate handling during angiotensin converting enzyme inhibition in unilateral renal artery stenosis. PMID- 1292351 TI - Immunogenicity of a recombinant hepatitis B vaccine in hemodialysis patients. PMID- 1292353 TI - [The effect of the characteristics of maternal psychological adaptation on the outcome of labor]. AB - The authors analyze the effect of psychologic adaptation of 108 pregnant women to the clinical course of their labor. Psychologic adaptation of pregnant women was assessed by the method of comprehensive personality analysis (the adapted variant of the Minnesota personality questionnaire). Two groups of women were distinguished: Group 1, 30 women (27.7%) with effective psychologic adaptation and Group 2, 78 women (72.3%) with disordered psychologic adaptation abilities. Disco-ordination of the uterine contractions (primary and secondary uterine inertia, early rupture of amniotic membranes, abnormal preliminary period), fetal and neonatal hypoxia, injuries to the soft tissues of the birth routes were more often observed in Group 2 women than in Group 1. PMID- 1292352 TI - [Pregnancy and labor in women in the region of the accident at the Chernobyl Atomic Electric Power Station]. AB - The authors analyze the tentative results of a multiprofile study, including a review of labor histories, examinations of pregnant women and parturients, measurements of fetoplacental hormones, study of the immunity status and microbiocenosis of the mothers and newborns, living in the first (up to 15 Ci/km2) and second (15 to 40 Ci/km2) zones of radioactive contamination. The detected shifts of a compensatory nature were found mostly in women living in the first zone. The disorders found in the women living in the second zone evidenced a decrease of the defense potential of the body, this necessitating nonspecific and correcting therapy during pregnancy, in labor and the postpartum period. PMID- 1292354 TI - [The acupuncture prevention of anomalies in labor strength in pregnant women of a risk group]. AB - Acupuncture was carried out for 3-6 days in the course of preparation to labor of 80 pregnant women at risk of developing labor activity abnormalities. Pulmonary, renal, gastric meridians, anteromedian and auricular points were used. Acupuncture was conductive to improvement of the autonomic nervous system activity with the predominance of the cholinergic component. The course of spontaneous labor was normal and blood loss was significantly lower than in puerperae not administered acupuncture. PMID- 1292355 TI - [A clinico-experimental study of the tocolytic properties of salbupart in treating threatened abortion]. AB - Clinical and experimental studies have revealed that salbupart, a beta-mimetic agent, administered in a dose of 0.14 mg/kg (the maximal therapeutic dose) markedly inhibited the spontaneous and oxytocin-induced uterine contractility, caused no embryotoxic or teratogenic effects, and did not influence fetal growth and development. The efficacy of salbupart tocolytic therapy was estimated as 75%. Blood plasma cAMP levels normalized in the pregnant women over the course of therapy. Clinical and experimental results recommend salbupart for pregnancy protecting therapy in cases with threatened spontaneous abortions. PMID- 1292356 TI - [New aspects of the surgical procedure in abdominal delivery]. AB - A single-row suturing of the incision on the uterus after cesarean section with separate muscular-muscular sutures by synthetic dissolving threads holds good promise. Such suturing helped optimize the reparative processes in the uterine cicatrix and reduce the incidence of postoperative pyoseptic complications. Kaproag, an antibacterial suture material made in this country, proved to be the best for the purpose. PMID- 1292357 TI - [The ultrasonic diagnosis of intrauterine fetal growth retardation]. AB - A total of 256 pregnant women were examined in pregnancy terms of 19-40 weeks. Besides routine fetometric parameters, the transverse diameter of the cerebellum was measured in the fetuses. This parameter was in good correlation with the gestational age. In 42 cases with small-for-date fetuses the transverse diameter of the cerebellum did not much differ from that in the reference group. Therefore measurement of the transverse diameter of the cerebellum is a truly good method for the assessment of the gestational age, for it is virtually independent of all the pathologic processes in the mother or fetus. PMID- 1292358 TI - [The ultrasonic antenatal diagnosis of rarely encountered tumors in fetuses and the procedure for managing the pregnancy and labor]. AB - Ultrasonic examinations of 3000 pregnant women revealed congenital developmental defects in 22 (0.7%) fetuses: in 4 cases tumors of various sites were detected and in 2 cases the tumors were found in one of the twins. Pathologic and histologic examinations carried out after delivery revealed a sacrococcygeal teratoma and a retroperitoneal dermoid cyst in one fetus, a ganglioneuroma of the retroperitoneal space, located between the bladder and rectum, an intrapericardial teratoblastoma, and a cystic cervical lymphangioma. The latter three tumors were responsible for nonimmune fetal edema. In one case an abortion was induced at pregnancy term of 22 weeks. Three fetuses died after deliveries in various terms. Based on his own experience and the literature data, the author suggests recommendations on the policy of following up the pregnancy and labor in various periods of gestation with different number of fetuses with due consideration for the tumor size and the fetal state, as well as on the possible correction after birth. PMID- 1292359 TI - [Fractures as a possible complication of osteoporosis in women in the climacteric]. AB - The author has analyzed the incidence of bone fractures in women of various age groups, residents of the Cheryomushki District of Moscow in 1988-1989, using the records of the traumatologic service of the district and the census data. The incidence of bone fractures was the highest in women aged over 45 (up to 2.5%), and was the higher the older the woman grew, 2/3 of all the fractures occurred in women aged 45-64. Analysis of the findings has confirmed that the developing postmenopausal osteoporosis, that was not diagnosed in time and therefore not prevented, contributed to the occurrence of bone fractures in women aged 45 to 65. The author emphasizes the necessity of studying osteoporosis incidence in various age groups and the share of this condition in women with fractures, making use of the monophoton absorptiometry. PMID- 1292360 TI - [A clinical trial of a monophasic contraceptive preparation containing ethinyl estradiol and desogestrel]. AB - A multicenter trial was conducted in 267 centers in Italy to evaluate the efficacy, acceptability and safety of a monophasic oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms desogestrel (Marvelon). 13,290 women were followed up for a total of 74,967 cycles. No pregnancies due to method failure were reported and only three because of patient failure. Cycle control was good. There was a decrease in the occurrence of irregular cycles and in the duration and amount of menstrual bleeding; the incidence of breakthrough bleeding and spotting was low. No severe side effects occurred and the incidence of minor complaints was generally lower during treatment than in the pretreatment cycle. Body weight and blood pressure were not significantly altered. PMID- 1292361 TI - [Superovulation and intrauterine insemination with treated spermatozoa in treating infertility--the first results of using the method in an urban obstetrical-gynecological hospital]. PMID- 1292362 TI - [Immunological changes in women with infertility of an inflammatory origin and their correction]. PMID- 1292363 TI - [The effect of individual placental proteins on the immunoregulatory cells of women with a normally proceeding pregnancy and with one complicated by abortion]. PMID- 1292364 TI - [The characteristics of the phospholipid spectrum of the blood serum and of the erythrocyte membranes in patients with hyperplastic processes of the endometrium and cancer of the corpus uteri]. PMID- 1292365 TI - [The results of dissertation work in obstetrics and perinatology approved by the Higher Certification Commission of the USSR in 1990]. PMID- 1292366 TI - [The treatment of underlying diseases of the cervix uteri in young women who have not given birth]. PMID- 1292367 TI - [Changes in the indices of the immune and protease inhibitor systems in physiological pregnancy]. AB - Studies of the immune and enzymic homeostasis in 26 healthy nonpregnant women and in 30 healthy pregnant women in the course of pregnancy and on days 2-3 after normal labor have revealed that the T immunity system was liable to changes over the course of pregnancy to a greater measure than the B system. A significant elevation of the neutral proteinase activity and slight fluctuations in acid proteinase activities were seen in pregnant women as against nonpregnant ones. Immunoglobulins A, M, G, circulating immune complexes levels and elastase activity and the total activity of antiproteinases were virtually unchanged in pregnancy. PMID- 1292368 TI - Stereo architecture of the connective tissue cores of the lingual papillae in the treeshrew (Tupaia glis). AB - The stereo architecture of the lingual connective tissue cores (CTC) in the treeshrew (Tupaia glis) (which has the primitive characteristics of primates) was observed by scanning electron microscopy, and compared to that of other animal orders. The tongue of the treeshrew has three vallate papillae which are situated in the posterior part of the tongue, while some macaques have several vallate papillae. Among numerous filiform papillae, fungiform papillae are sporadically distributed. A filiform papilla consists of a bundle of several slender spine like processes arranged in a circle at the basal margin. After removal of the epithelium, the CTC of the filiform papilla looks like a human hand raised with the palm facing towards the tongue tip. The fungiform CTC in the threeshrew is columnar in shape (rather similar to that of Insectivora and Rodentia) and at the top there are several round depressions for taste buds. In the treeshrew several large rod-shaped processes are derived from the postero-lateral margin of the tongue, as in Carnivora (dogs and cats), where foliate papillae are located in many other animal species. The treeshrew has numerous characteristics similar to those of the crab-eating macaque (Primates), but at the same time it has some characteristics similar to those of Insectivora, Rodentia, Carnivora and Artiodactyla. PMID- 1292369 TI - The cellular network of interstitial cells associated with the deep muscular plexus of the guinea pig small intestine. AB - Systematic examination using electron microscopic montages and serial sections has demonstrated that three types of interstitial cell, namely gap junction-rich cells, glycogen-rich cells and fibroblast-like cells, are densely located along the whole extent of the deep muscular plexus of the guinea pig small intestine. They tend to be distributed in an alternating fashion in the cellular network, connected with muscle cells of the outer, circular layer by means of gap junctions. These three types of interstitial cell show close relations to two types of nerve varicosity: one type is characterized by clear round vesicles with diameters of about 50 nm, and the other by flattened vesicles measuring about 35 nm by 70 nm. Electron-dense patches have been observed at the cytoplasmic side of the axonal membranes. Muscle cells of both inner and outer circular layers also show close relations to these two types of nerve varicosity. These morphological features are discussed with the implication that they may have some regulatory role in intestinal movement. PMID- 1292371 TI - Human mandibular prenatal growth: bivariate and multivariate growth allometry comparing different mandibular dimensions. AB - Mandibular growth was studied in 36 human fetuses (both sexes) ranging from 13 to 37 weeks of gestation by bivariate and multivariate analyses (bivariate allometry and principal components analysis, PCA). Several mandibular dimensions were measured and correlated with fetal weight. Considering the different mandibular dimensions in sequence of increasing component weights, PCA agreed with bivariate analysis. No mandibular dimension was considered to increase in isometric relationship. PCA showed the following distances with negative allometry: caput mandibulae-gnathion (both sides), gonion-processus coronoideus (both sides), caput mandibulae-processus coronoideus (both sides) and gonion-gnathion (right side). On the other hand, the following dimensions grew with positive allometry: gonion-gnathion (left side) and symphyseal height (both sides). PCA and bivariate analysis showed higher growth rates for the gonion-processus coronoideus distance and symphyseal height on the right side than on the left. All other mandibular dimensions presented more elevated growth rates on the left than on the right side. During the second and third trimesters of prenatal life the mandibular growth was allometrical; the mandibular body grew with more intensity than the ramus in both length and height. The greatest growth rate was found for the height at the symphysis. The angulus mandibulae presented a negative and slight correlation with the other linear dimensions of the mandible during prenatal life. PMID- 1292370 TI - Ultrastructural localization of calcium in the chick chorioallantoic membrane as revealed by cytochemistry and X-ray microanalysis. AB - The chorioallantoic membrane (CAM) of the chick embryo actively transports calcium from the egg shell into the embryonic circulation. To investigate the intracellular pathway of calcium transport across the CAM, ultrastructural localization of intracellular calcium in cells of the chorionic ectoderm (CE) was determined using cytochemical methods and X-ray microanalysis. Treatment of the CE with potassium oxalate, potassium ferricyanide or potassium pyroantimonate revealed large numbers of electron-dense granules (EDGs) in the ectodermal cells. These measure 30-40 nm in diameter, and are not membrane-bound. These granules were seen in all three cell types of the CE. The presence of calcium in the EDG was directly confirmed by X-ray microanalysis. When strontium or barium ions were applied to the shell membrane side of the CAM, the cells of the CE incorporated these divalent cations and sequestered them in granules (25-40 nm in diameter) in cytoplasm and mitochondria. This study indicates that calcium enters the CE cells by means other than endocytosis, as the EDGs are not membrane-bound, that all three types of the CE cells appear to function in transport of calcium from shell to embryo during embryogenesis, and that the EDG plays important roles in intracellular accumulation of calcium during the process of calcium transport across the chorioallantoic membrane. PMID- 1292372 TI - Ultrastructural and immunocytochemical study of the myoendocrine cells of the fish Hypostomus cordovae. AB - The myoendocrine cells of the heart of Hypostomus cordovae (Gunther 1880), a teleost fish from South America, were investigated by electron microscopy and immunohistochemistry. By applying antibodies raised against synthetic cardiodilatin 99-126 (CDD/ANP 99-126), a specific labeling of this hormone was found in the heart of this fish, mainly in myoendocrine cells of atrial trabeculae, where specific secretory granules are stored. The distribution of secretory granules exhibited striking seasonal variations. In winter there were fewer differentiated myoendocrine cells, which were easily recognized by the presence of specific secretory granules, most of which occur clustered in perinuclear areas of the cells. By contrast, in summer the majority of the myocardic cells of the atrium are active endocrine cells. They contain abundant secretory granules widely scattered in the cytoplasm, many of them polarized toward the subendocardial aspect of the cell. The secretory granules can be easily differentiated from the Weibel-Palade granules of endothelial cells, the shape, size and content of which were typical at electron-microscopic level. In addition, these endothelial granules did not display CDD immunoreactivity. The presence of cardiodilatin in a fish such as Hypostomus cordovae further supports the view that cardiac hormones are present in many Vertebrates and may preserve analogous roles such as those reported in other species throughout the group. PMID- 1292373 TI - Number and size-spectra of myelinated nerve fibers of human premolars. AB - The primary objective of this study was to determine the number and size of myelinated nerve fibers at the subcervical, midroot and juxta-apical levels of human premolars. Sixty-seven healthy premolars extracted from adolescents were utilized. Root-discs were prepared from the three sites and processed for light and electron microscopy. The myelinated nerve fibers were counted from semithin sections using a sampling microscope. The measurements were taken from composite electron micrographs using an electronic image processing unit. A total of 1883 myelinated axons from seven mandibular second premolars was gauged. The 67 teeth had an average of 312 +/- 149 myelinated nerve fibers at the juxta-apical level (range 18 to 728). The contra- and ipsilateral differences in means among the four groups of premolars were not significant (P > 0.05). The number of nerves increased significantly (P < 0.05) toward midroot and subcervical (P < 0.001) levels in all groups. The average neural diameter was 3.5 + 1.0 microns at the juxta-apical level, and the between-teeth difference in mean was found to be significant (P < 0.01). There was no decline (P > 0.05) in the diameter of myelinated nerve fibers toward midroot and subcervical levels. PMID- 1292374 TI - An ultrastructural study of myoepithelium maturation during postnatal development of the hamster Harderian gland. AB - This study reports the ultrastructural cell modifications in the myoepithelium of the Harderian gland during the postnatal development of the Syrian hamster. Tissues were obtained from male and female hamsters at days 1, 3, 5, 7, 10, 12, 15, 17, 20, 27, 37, 46 and 90 after birth, and processed for transmission electron microscopy. Electron microscopy was coupled with point counting methods to quantitate changes in several subcellular organelles during the course of myoepithelial cell maturation. The myoepithelial cells in this gland remained immature at birth. The earliest age of development when organized bundles of microfilaments were observed was 7 days. By the 12th day, the myoepithelial cells had developed most of their specific characteristics and resembled the mature form. Myoepithelial cells mature synchronously with each other and with the secretory cells. No undifferentiated myoepithelial and myoepithelial cells, the secretory endpieces of the adult hamster Harderian gland contain a third cell type which resembles the myoepithelial cell in shape and has an extremely electron-lucent cytoplasm lacking microfilament bundles. PMID- 1292376 TI - Development and ageing of phenotypically distinct fibrocartilages associated with the rat Achilles tendon. AB - We describe by routine histology and by immunohistochemistry three phenotypically and developmentally distinct fibrocartilages associated with the Achilles tendon of the rat. All the fibrocartilages develop after birth and show significant age related changes in the composition of their extracellular matrix. Attachment-zone fibrocartilage occurs at the insertion of the tendon on the calcaneus. It derives from the cartilage rudiment of the calcaneus and from the region where the tendon merges with the perichondrium. The extracellular matrix contain type II collagen and chondroitin sulphate. Compressive tendon fibrocartilage occurs in the deep part of the tendon where it presses against the calcaneus, and is derived by metaplasia of tendon cells. The cells label strongly for the intermediate filament vimentin, and the extracellular matrix contains chondroitin and keratan sulphates, but type II collagen only in very old animals (> 2 years). Calcaneal fibrocartilage covered the posterior surface of the calcaneus where it was in contact with the Achilles tendon. It labelled intensely for type II collagen and contained chondroitin and keratan sulphates. The cells were rich in vimentin. This fibrocartilage was derived from the calcaneal perichondrium. PMID- 1292375 TI - Fiber order in the opossum's optic tract. AB - The distribution of axons by size in the optic tract of the South American opossum, Didelphis marsupialis was studied. Thin and semi-thin sections were examined, and measurements of axonal diameter were made on electron micrographs taken from various locations across the optic tract of normal opossums. In order to determine the contributions of the different axon diameter classes to the crossed and uncrossed retinofugal pathways, measurements were also made from the tracts of opossums in which one eye had been enucleated 5 weeks previously. Within the opossum's optic tract, the axons are partially segregated by their size: the deepest parts of the tract contain only fine and medium-sized axons, whereas coarse axons are also present superficially. In the middle of the tract, all three size classes are present. At increasingly superficial positions, there is a steady reduction in the proportion of medium-diameter axons, and an increase in the number of the finest axons. Medium and coarse axons contribute to both the crossed and uncrossed pathways, and the uncrossed component is displaced superficially relative to the crossed component. The fine axons in the deeper parts of the tract arise from both retinae, while those in the superficial parts of the tract, near the pial surface, are virtually all crossed. The opossum's optic tract thus displays the segregation of axons by size found in placental mammals, and follows a pattern reminiscent of that found in carnivores. Such a common organizational plan, particularly the similarities between the didelphids and carnivores, is suggestive of an early acquisition of parallel visual pathways in mammalian phylogeny. Since the fiber order in the optic tract of eutherians is a chronological map of axonal arrival during development, these results suggest that a conserved developmental mechanism has led to a common organizational plan. PMID- 1292377 TI - [Intra- and extracranial nasopharyngeal fibroma. Contribution of imaging and study of local failure. Report on 34 patients]. AB - Thirty-four patients with nasopharyngeal angiofibroma were treated between 1975 and 1990. Lesions were classed according to Sessions' classification. 17 showed intracranial extension. Treatment always associated embolization and surgical excision using a transfacial approach and, if necessary, neurosurgical techniques. A total of 13 patients (38.2%) developed recurrent lesions; these included 3 (17.6%) patients in the extracranial group and 10 (58.8%) patients in the intracranial group. Erosion of the clivus and displacement of the cavernous sinus seem to be 2 factors significantly associated with the development of recurrent lesions. Symptomatic recurrences were managed by surgery. Close clinical and radiological follow-up of patients with asymptomatic recurrent tumor made it possible to observe the stabilization, or even, the regression of the tumor. This study also underlines the importance of modern diagnostic and interventional imaging, which makes it possible to better determine tumor extension and to perform highly selective embolizations. Modern imaging also detects recurrences which once would have remained unknown because of their small size and the absence of symptoms. The techniques of embolization of the tumor branches from the internal and external carotid arteries are explained. Finally, our results are compared to those published in the literature. PMID- 1292378 TI - [Partial posterior cordectomy with laser CO2 in bilateral recurrent paralysis]. AB - Thirteen patients with bilateral vocal cord abductor paralysis were treated by Carbon Dioxide Laser Posterior Cordectomy. 6 out of 7 patients were decannulated. 92% of patients recovered a physiologic respiration. Advantages of this surgical technique are discussed in comparison with Endoscopic Laser Arytenoidectomy. PMID- 1292379 TI - [Cervical branchiomeric paraganglioma. Report of 21 cases]. AB - Over the last 24 years the authors operated 21 branchiomeric paragangliomas in 18 patients. They emphasize the difficulty of making the diagnosis and the importance of completing a thorough work-up before deciding surgery. Adequate imaging is particularly important (neck sonography, computed tomography, arteriography) to avoid making the diagnosis by exploratory neck dissection and to assess the vascular risk. Biological studies have regained importance, especially in the context of complex neuro-cristopathy. Treatment is essentially surgical and must be considered with prudence in patients with bilateral lesions. The surgical removal of branchiomeric paragangliomas necessitates preparation of a small saphenous vein bypass in case it is not possible to avoid sacrificing the internal carotid artery. PMID- 1292380 TI - [Revision intranasal sphenoethmoidectomy in recurrent nasosinusal diseases especially polyposis]. AB - A 16 case series of intranasal revision sphenoidecthmoidectomies is presented in this study concerning 10 patients with recurrent polyposis after 245 intranasal ethmoidectomies performed between 1986 and 1990 (6.5%). The modalities of surgical decision are precisely described, pointing out the correlation between clinic and endoscopic arguments. The CT-Scan is particularly appreciated for the details of recurrence sites and the anatomical dangers along these recurrences. Comparison is established with the most recent publications in this field and the discussion is open to express the rules of this surgery. 80% of good and excellent results are obtained in this series, justifying the procedure. The causes of bad results are evocated, especially allergy and the age of polyposis. PMID- 1292381 TI - [Long-term follow-up and therapeutic results of the protocol of the National Society of Internal Medicine in centrofacial malignant granuloma. Report of 40 cases]. AB - We have studied 40 cases of mediofacial necrosis with no specific diagnosis on biopsy. After an exhaustive work-up we reached a specific diagnosis in 13 patients (Wegener's granulomatosis in 7, classical malignant lymphoma of the nose in 3, squamous cell carcinoma = "goundou" in 1, syphilis and tuberculosis in 1, aspergillosis in 1). Those patients received the appropriate treatments with good results. The remaining 27 patients, however, had ulcerative lymphomas of the midface (according to the immunofluorescence and molecular biology techniques). Their fate was worse since only 15% remain alive on the long-term, despite intensive treatments with chemotherapy, radiotherapy, interferon, artificial nutrition and antibiotics as needed. We present a new protocol with intensified chemotherapy and growth factor treatment in order to ameliorate the very poor prognosis of these patients. PMID- 1292383 TI - [Secretory eosinophilia and obstructive rhinitis]. AB - Detecting eosinophilia in the nasal secretions of patients complaining of nasal obstruction makes it possible to identify a group of high risk patients. Hosty use of surgery in these patients carries a high risk of iatrogenic complications and little potential for improvement. The 2 most frequently used methods of obtaining cytologic specimens (swabbing versus washing) were compared in 37 patients with obstructive rhinitis (early stage polyposis and nonallergic rhinitis with eosinophilia syndrome, NARES). Swabbing gave reliable results. Eosinophilia was negligible in a group of 25 control subjects. The mean eosinophil count was 2.5% and only 1 patient had a positive cystogram. The 220 patients which nasal obstruction were classed in 5 groups according to the severity of clinical signs and symptoms. The mean eosinophil count and the percentage of patients with positive cystogram increased with increased severity of the clinical syndrome. 28 patients had uncomplicated obstructive rhinitis, 10 had NARES, 43 had allergic rhinitis, 52 had chronic obstructive rhinitis, and 87 had nasosinal polyposis. The respective mean eosinophil counts were 6.42%, 10.3%, 13.8% 16.8% and 31.4%. The percentage of patients with positive cytograms was respectively, 10.8%, 20%, 23.3%, 28.8% and 54%. PMID- 1292382 TI - [Cystic lymphatic malformations of the head and neck. Role of interventional radiology]. AB - Cystic lymphatic malformations are hemodynamically inactive vascular malformations of the lymphatic compartment. Over a 9 years period, 52 patients with superficial cystic lymphatic malformations of the head and neck underwent embolization by direct injections of Ethibloc (Ethicon, Ethnon Laboratories, Neuilly/France) under fluoroscopic control. Results were graded as excellent or good in 57% of patients after embolization alone. Treatment was completed by surgery in 19% of patients. Embolization was considered a failure in 24% (12 patients), although 10 of these patients showed regression of the cystic component after embolization. This safe, efficacious percutaneous technique has emerged as the first treatment to be considered for cystic lymphatic malformations. PMID- 1292385 TI - The burns scene in Singapore--past, present and future. PMID- 1292384 TI - [Treatment of epistaxis in Rendu-Osler disease by intramucosal injection of ethibloc]. AB - The authors relate their one-year experience in percutaneous embolization of 12 patients presenting with severe epistaxis because of a Rendu Osler disease. Using Ethibloc a sclerosing substance derived from maize in direct intramucosal injection seems to be a promising technique. Ethibloc is still used successfully in percutaneous treatment of superficial venous angiomas. PMID- 1292386 TI - The burned ear (I): An experimental study with the rabbit model to evaluate scalding temperature, surface and histopathologic appearance, and healing responses with depth of injury. AB - There are few papers on experimental burns of the external ear. An experimental model was made and a study was conducted on 18 white rabbits to evaluate the response of the rabbit ear in relation to temperature, surface and histologic appearances and healing response with depth of injury. The rabbit model showed that: a) the rabbit ear resembled that of the human ear in histological structure. b) there was a definite correlation of the temperature of the scalding agent with the depth of the injury. c) it was possible to classify morphologically the depth of injury based on surface appearance. d) there was an accurate morphologic correlation with that of histopathologic assessment of burns depth. e) the sequential biopsy at different times (immediate, third, fifth day) showed that the depth of the burns was already apparent soon after the injury. f) there was also a correlation of burns depth with the rate of ear healing. PMID- 1292387 TI - The burned ear (II): A prospective clinical study of 100 patients with 150 ear burns. AB - A prospective clinical study of 100 patients with 150 ear burns was carried out in the Burns Centre, Singapore General Hospital. The aims of this study were to document the nature of the injury, the results of various methods of treatment, the complications of ear burns and the changes that led to chondritis. Based on the findings of the experimental studies on the burned ear, it is possible to accurately classify the depth of the burn injury based on the surface appearance. The results show that fire was the commonest aetiologic agent for ear burns (65% cases) and hot water scalds second (25% cases). Scalds tended to cause unilateral ear burns whilst fire caused bilateral injuries. The single most important factor in healing of the burned ear was the depth of the injury. Erythema took six days, mid-dermal (MD) burns ten days, uncomplicated deep-dermal (DD) and full thickness (FT) burns 35 days. When chondritis developed deep dermal burns took 43.5 days to heal and full thickness burns took 57.8 days. Conservative treatment of 104 ears resulted in complete healing except for 15 which had pigmentary and/or hypertrophic scar problems. Surgical treatment was used in 23 ears. Three returned to normal appearance, eleven had mild and four had moderate deformities. Five ears were lost (3% cases). Chondritis was present in 12 ears (8% cases), six in DD and six in FT burns. Seven of these ears were successfully salvaged. Favourable results in this study were attributed to the following factors: early detection of chondritis by the EAR SPRINGING SIGN, early surgical intervention, radical cartilage removal, meticulous post-op care to prevent cross infection and avoidance of pressure to the ears. PMID- 1292388 TI - Epidemiology and management of respiratory burns in National Burns Centre, Singapore. AB - Respiratory burns constitute one of the two leading causes of burns mortality today, the other being infection. When cutaneous burns are complicated by co existent respiratory or inhalational injury, the mortality remains high in most reported series. We began our prospective study of respiratory burns in 1982 as a multi-disciplinary team effort involving respiratory physicians, anaesthetists and our burns physicians. Between 1982 until February 1990, we treated a total of 240 patients with respiratory burns. During the same period, a total of 4041 patients were admitted to our Burns Centre at Singapore General Hospital. Respiratory burns cases therefore constituted 5.4% of the total burns admissions. In our series, there were 44 deaths out of 240 patients, giving an overall mortality of 18.3%. The average size of burns in the patients who died was 57.4% BSA in Group A patients, 65.0% BSA in Group B and 57.7% BSA in Group C. Our management protocol has gradually evolved over the eight years of the study. Systemic antibiotics and steroids are no longer used routinely. Fiberoptic bronchoscopy is done early in the ward as a bedside procedure once a patient is clinically assessed to have suffered a respiratory burns and repeat bronchoscopic examination done when deemed necessary. An aggressive regime of respiratory support measures with early intubation and PEEP ventilation is recommended. PMID- 1292389 TI - Morbidity and mortality in respiratory burns--a prospective study of 240 cases. AB - A prospective study of 240 consecutive admissions with respiratory burns over an eight-year period beginning 1982 was carried out at the National Burns Centre, Singapore General Hospital. Diagnosis of respiratory burns was based on clinical criteria and a clinical score was then computed to grade the severity. Investigations included chest x-rays, blood gases, carboxyhaemoglobin level, lung scan and fibreoptic bronchoscopy. Treatment was carried out according to a standard protocol where a policy of early intervention in the form of endotracheal intubation was emphasised. Other respiratory support measures were chest physiotherapy, tracheobronchial suction, mucolytics and bronchoscopic lavage where indicated. We found that respiratory burns was a significant cause of mortality in burns patients. The influence on mortality was most marked in patients with large body surface area burns of more than 40%. Age was also an important determinant of survival with patients older than 50 years faring significantly worse. The routine steroids and prophylactic antibiotics did not influence the survival rate. Carbon monoxide poisoning was not a significant cause of mortality. We achieved an overall mortality rate of 18.3%, with 44 deaths out of 240 patients. The main causes of deaths at post-mortem were bronchopneumonia, septicaemia and extensive burns. PMID- 1292390 TI - Mass ammonia inhalational burns--experience in the management of 12 patients. AB - Twelve Korean crew members of a deep sea fishing vessel were admitted to the Burns Centre, Singapore General Hospital following exposure to ammonia gas. The injuries sustained were primarily respiratory burns with minor cutaneous and corneal burns. They were divided into three grades of severity based on the admission findings and subsequent clinical course. Management was according to a standard respiratory burns protocol. Eight patients were intubated. Ten of the patients with mild and moderate involvement of the respiratory tract recovered without complication. Of the two patients with severe respiratory burns, one died while another progressed to chronic debilitating airway disease. PMID- 1292392 TI - Burns mass disasters: aetiology, predisposing situations and initial management. AB - Many agents that are encountered daily are liable to cause burns mass disasters. These include flames, hot water and steam, combustible gases and liquids, molten liquids, boiling liquid expanding vapour explosion, chemicals and explosives. They result in disaster when certain lacks in safety occur. The proper management of such burns victims begins with rescue. At the disaster site, triage is important to separate the living from the dead, decide on priorisation for initial treatment and then evacuation to an appropriate facility. Proper management requires team effort and should be continued en-route to hospital. Repeat triage and use of clear guidelines in the Emergency Department ensure optimal and rapid care of the casualties. Finally psychological support for victims, relatives, rescuers and health workers must not be forgotten. PMID- 1292391 TI - Radionuclide lung scanning in the management of respiratory burns. AB - Soluble radioaerosols such as technetium-99m diethylene triamine pentacetate (DTPA) permit simple quantitative studies of alveolar-capillary permeability to be performed, since the submicronic aerosols are deposited mainly at the lung periphery and are cleared across the alveolar-capillary membrane. Regional alterations in permeability can also be noted using this radionuclide technique. We have measured the alteration in pulmonary epithelial permeability in normal subjects and in patients with inhalation burns using a computer-linked gamma camera. In the normal volunteers, the time taken for 50% of inhaled Tc-99m DTPA to be cleared from the lungs (T1/2) was 66 minutes +/- 1sd of 12 minutes. In the 42 patients with inhalation burns, besides the T1/2, retention images of uncleared Tc-99m DTPA in the lungs were obtained to note regional differences, if any, in lung clearance arising from pulmonary epithelial damage; these patients showed increased rate of clearance (short T1/2) with mean T1/2 of 36 minutes +/- 1sd of 11 minutes, while the retention images revealed regional lung damage in moderately severe inhalation burns. In 18 patients with abnormal T1/2, 16 (89%) had abnormal bronchoscopy findings. Fifteen patients also had lung perfusion scans with Tc-99m MAA (macroaggregated albumin). The regional defects in perfusion when present were generally matched with the defects seen on ventilation scans. The Tc-99m DTPA lung clearance measurement and imaging has clinical usefulness in suspected inhalation burns. PMID- 1292393 TI - Anatomy of a burns disaster: the Miri Bank explosion. AB - A bank explosion in a neighbouring country over 1000 km away resulted in ten badly burned victims being airlifted to the Burns Centre, Singapore General Hospital (BCSGH) for treatment. The severely injured included patients with 90%, 80%, 74%, 66%, 45%, 33% and 31% burns. Nine had respiratory burns (four severe, one moderate, four mild). One patient died, thus, the mortality rate for the six most severely injured was 16.7%. This differs from predicted mortality rates of 78% according to McCoy or 54% according to Thompson, Herndon et al. The factors contributing to this result were the small size of the disaster, the use of an established Burns Mass Disaster plan and an individual management policy that incorporates carefully monitored fluid resuscitation, recognition of respiratory burns with early treatment by intubation thus pre emptying complications, early surgery and a multidisciplinary approach to complications such as infection and renal failure. The average length of stay was 43 days (range 5-122 days). The cost of the hospitalisation of the ten casualties was $312,317.00. PMID- 1292394 TI - Forensic investigation of deaths due to fire in mass disaster. AB - When a body is recovered from a fire site, it is essential to determine if death occurred before or after the fire started. Foul play is suspected when there is an alternative cause of death not due to the fire. In cases of mass disaster due to fire, the forensic pathologist has an additional task of identifying the bodies. This is important in medico-legal investigations. The severity of the burnt injuries sustained may be useful in the reconstruction of the incidence. Examples will be given in this paper on the identification of the burnt victims and the forensic investigations on death by fire in mass disasters. PMID- 1292395 TI - The prevalence of invasive candidiasis in patients with extensive burns. AB - A retrospective study of patients admitted to the Singapore General Hospital Burn Unit with > 30% total body surface area burns was performed to establish the prevalence of fungal colonisation and invasive fungal disease (IFD). Forty-eight percent of patients surviving at least ten days following thermal injury had fungi isolated. IFD was documented in ten patients. Risk factors associated with the development of IFD, clues to assist in diagnosing IFD, and therapeutic options for managing IFD are reviewed. PMID- 1292396 TI - Emergence of a multiply-resistant strain of Acinetobacter in a burns unit. AB - Multiply-resistant Acinetobacter has emerged as an important organism in the Burns Unit of the Singapore General Hospital. From November 1990 onwards, a strain that was resistant to all antibiotics except Polymyxin B emerged in the Burns Unit. We present two cases where the Acinetobacter isolated was resistant to all antibiotics including Polymyxin B. These cases serve as an important reminder to adhere to strict infection control procedures. PMID- 1292397 TI - Multiple resistant Staphylococcus aureus. AB - Burn wound sepsis is still a common cause of death in burn injuries. Eighty percent of this infection is with colonisation from the patient and twenty percent as a result of cross infection. Most of the mortality is due to virulent cross infection. Pseudomonas has almost disappeared and multiple resistant staphylococcus aureus is the main pathogen today. It can cause loss of skin grafts and septicaemia, particularly due to colonisation of intravenous lines. The risk increases with the time since the burn injury. Early excision and grafting is important. With a large burn it is not possible to do this in one session and so the risk is increased with a compromised patient. Maintenance of a good diet and vitamin supplements is important, preferably orally or through a naso-gastric tube. Parenteral nutrition increases the risk of infection. Clinical infection is combated by good cleaning procedures, preferably with chlorhexidine solution and the application of a good topical agent such as Silvazine. The presence of bacteria in the wound must be monitored. Strict barrier nursing and personal hygiene, particularly hand washing, are the mainstay of cross infection prevention. Antibiotics may be required, monitored by blood cultures. Documenting MRSA is a good way to monitor the unit's infection prevention programme. The main preventive measures are early referral, early excision and grafting, good nutritional support, good topical agents and barrier nursing. PMID- 1292398 TI - Epidemiology of burns in Singapore children--an 11-year study of 2288 patients. AB - A retrospective review of 2288 children (12 years and below) admitted to the Burns Centre, Singapore General Hospital over an eleven year period (1978-1988) was made. Annual admissions from 1978-85 ranged from 208-290 cases annually (32 38% of all admissions). Between 1986 to 1988 annual admissions ranged from 73-104 cases annually (22-28% of all admissions). There was a reduction of number as well as proportion of children admitted. The main reasons for this change in trend were due to the successful nationwide campaign on fire and home accident prevention, change in admission policy and introduction of newer dressings to treat smaller burns. Boys accounted for 62% admissions. Toddlers between the age of one to two were most vulnerable (26% admission) and children under three years of age accounted for 50% admissions. Eighty-five percent of burns admitted were 10% or less. Length of stay ranged 8-12 days. The commonest cause of injury was scalds (90%) and flame burns (6%). Flame was responsible for the death of six children and scalds of three children. There were nine deaths in this series giving a mortality of 0.4%. Children mortality contributed to 5.6% of total mortality seen in our burns centre. Age per se did not contribute to a higher mortality. There was a definite correlation of mortality to extent of burns. Only one child died from burns of less than 40%. Case mortality in the 40-60% burns group was around 20% and it increased sharply when extent of burns reached or exceeded 70%. Burns in children exhibit anatomical, physiological, surgical, rehabilitative and psychological differences when compared to adults. PMID- 1292399 TI - Psychiatric disorders associated with burns. AB - A study was made of burns patients who were referred for psychiatric problems. There were a total of 69 subjects, divided into three groups. The first group comprised thirty-four cases who attempted suicide by burning themselves--there were more women than men, the majority were less than forty years, and Indians were overrepresented. The majority of these were suffering from schizophrenia or a major depressive disorder. The second group of twenty-three patients were those who had a non-psychotic psychological reaction to their burns. The majority were also less than 40 years of age, and the main reactions were anxiety neurosis or reactive depression. The third group of twelve patients were suffering from delirium. All were pyrexic and in eleven, infective agents were cultured. Some of them also had electrolyte abnormalities and two had respiratory burns. PMID- 1292400 TI - Going deep into chemical burns. AB - This is a five year retrospective study of chemical burn injury in our burn center between 1 January 1987 and 31 December 1991. Of the 1,226 total burn cases, 131 patients had chemical burns. We noted a constant prevailing incidence of 10.7% per year. Males (72%) are more common than females (28%). Most of those injured are in the working age group (65%). Majority of cases had deep full thickness burn involving less than 10% of their total body surface area. Sulfuric acid is the most common chemical agent encountered. We had three mortality cases with deep third degree burns covering 60% of their total body surface area. Some clinical cases are demonstrated. Lastly, proposed solutions for the prevention of chemical burns are cited. PMID- 1292401 TI - Escharotomy in burns. AB - The need for escharotomies is relatively common in the treatment of burn injuries. The need arises because the tight eschar may interfere with the circulation to a limb causing demarcation and loss of the limb or in the case of the chest, may cause interference with respiration such that the expansion in the lungs is interfered with causing atelectasis and pneumonia. In the neck the oedema in the tissue may cause obstruction to the trachea. Indications for escharotomy rest on clinical grounds with tension in the limb under the burn and the state of circulation to the periphery being important. Added to this is the use of Doppler ultrasound, clinical presence of peripheral pulses and at times compartmental pressure measurements. The aim of the escharotomy is to release the pressure over the involved deeper tissues and to restore their circulation. TECHNIQUE: Under sterile conditions make incisions through the eschar until the tissue gapes such as to release the pressure particularly on the vascular supply. These should avoid flexion increases and be designed to release pressure in all compartments if necessary. In the case of electrical burns this may need to be combined with a fasciotomy for diagnostic and therapeutic purposes. Bleeding must be controlled and the escharotomy is then treated as a burn injury being packed with Silvazine cream. Elevation of the limbs is important also to help limit the oedema. PMID- 1292402 TI - Skin graft and skin equivalent in burns. AB - The problem in extensive burns is the relative lack of available donor sites for skin grafting. Before the burnt areas can be covered, infection often sets in and the patients may then succumb. Skin grafts can be expanded in a limited way. Biological dressings or synthetic dressings can be used to buy time till donor sites become available. Cultured epithelium grown in the tissue culture laboratory permits massive expansion of skin and has been used with success as epithelial autografts in patients. Composite skin equivalents or skin substitutes have been developed and show promise. PMID- 1292403 TI - Cadaveric study on the vascular anatomy of the ulnar nerve at the elbow--a basis for anterior transposition? AB - The clinical results of anterior transposition of the ulnar nerve in compressive ulnar neuropathy have been unsatisfactory. This study aims at qualifying and quantifying the vascular anatomy of the ulnar nerve at the elbow so as to enable us to appreciate the possible effects of anterior transposition of the ulnar nerve. In our study of 16 cadaveric limbs, we found that the average number of nutrient vessels supplying the ulnar nerve is 14.3. The main contributing vessel in the arm is the superior ulnar collateral artery, at the elbow, the inferior ulnar collateral artery proximally, and the posterior ulnar recurrent artery distally. In the forearm, the main supply is from the ulnar artery. The average length of the nutrient vessels ranges from 1 cm at the elbow to about 2.6 cm in the arm. The nutrient vessels at the elbow are short, small and numerous. Blood supply to the nerve is segmental in nature. In our histological study of the nerve at the elbow, we found that overall, there are more vascular channels in the intrinsic system than the extrinsic system (statistical significance p < 0.01). From this study, we were able to postulate that there is devascularisation of the ulnar nerve following an anterior transposition. The significance of the devascularisation will require further studies. PMID- 1292404 TI - Results of total hip replacement in renal transplant recipients. AB - A vascular necrosis of the femoral head associated with steroid immunosuppression is a cause of significant morbidity in renal transplant recipients. We review the results of 30 total hip replacements in 20 renal transplant recipients with a mean follow-up of 6.3 years. The mean age at the time of surgery was 35 years. The average Hospital for Special Surgery Hip Score was 17 points before operation and 32 points after operation. Fourteen hips were rated excellent and 12 hips rated good. There were four failures--one hip was revised for symptomatic loosening and three prosthesis were removed for infection. Twenty-seven of the hip replacements were subjectively rated as satisfactory by the patient. There was no significant difference in post-operative hip scores between cemented and uncemented prostheses. Total hip replacement in renal transplant recipients in this study has shown good long term result with a revision rate of about 3%. Late infection was a major problem with an incidence of 13%. Prophylactic antibiotics must be used whenever there is a risk of haematogenous seeding from transient bacteremia in these immunosuppressed patients. Use of uncemented prosthesis may make future revision arthroplasty easier. PMID- 1292405 TI - Tracheo-oesophageal groove clearance in well differentiated thyroid carcinoma. AB - Papillary carcinoma of the thyroid has a propensity for spread to the regional lymph nodes, in particular those along the recurrent laryngeal nerve. Twenty cases of papillary carcinoma of the thyroid had prophylactic clearance of the lymph nodes along the tracheo-oesophageal groove, and one patient had removal of recurrent disease in the groove. Eleven of the twenty patients had, in addition, some form of cervical lymph node clearance for clinically palpable ipsilateral cervical lymph nodes. Metastases to the tracheo-oesophageal groove lymph nodes was seen in seven of the twenty patients (35%). Tumour size, age, sex, race and cervical lymph node involvement did not appear to predict involvement of the tracheo-oesophageal groove lymph nodes. Clearance of the lymph nodes along the tracheo-oesophageal groove at the time of resection of primary disease is worthwhile for thyroid papillary carcinoma, because of the high incidence rate (35%) and also clearance for subsequent recurrence will be more difficult with a higher risk of damage to the recurrent laryngeal nerve and parathyroids. PMID- 1292406 TI - A successful peritoneovenous shunting of ascites using the great saphenous vein. AB - For the surgical palliation of massive ascites, a LeVeen or Denver shunt may be implanted to drain ascitic fluid from the peritoneal cavity into the circulation. But all commercial shunts are costly and depend on a synthetic valve to prevent blood refluxing into the peritoneal cavity. We report here the first patient with a malignant ascites that was successfully palliated by peritoneovenous shunting using the great saphenous vein as a biological valve. PMID- 1292407 TI - An assessment of preoxygenation techniques using the pulse oximeter. AB - The effect of preoxygenation with varying inspired oxygen concentration on the arterial oxygen saturation during induction of anaesthesia and intubation was studied using the pulse oximeter. Sixty-five healthy, young adults, (American Society of Anaesthesiologists Class I) undergoing elective surgery were randomly divided into three groups. Group I patients were not preoxygenated. Groups II and III patients were preoxygenated with 50% oxygen and nitrous oxide and 100% oxygen respectively for one minute. All were then induced with thiopentone, paralysed with suxamethonium and orally intubated. During intubation, severe arterial desaturation occurred in those patients who were not preoxygenated (lowest saturation was 81.7 +/- 7.8% occurring 87 +/- 24.5 seconds after suxamethonium injection). This was significantly lower than the other two groups (p < 0.001). No patient had clinical signs of hypoxaemia. Patients who were preoxygenated with either 50% oxygen and nitrous oxide or 100% oxygen showed similar and clinically insignificant desaturation during this period. One minute after intubation and manual ventilation with 100% oxygen, the saturations of all patients returned to preinduction levels. PMID- 1292408 TI - The aetiopathogenesis of craniofacial anomalies. AB - Craniofacial embryogenesis with emphasis on the mechanisms of morphogenesis as a basis for understanding developmental anomalies is reviewed. A classification of maldevelopment into malformation, deformation and disruption is illustrated by examples. A brief review of the clinical consequences of craniofacial anomalies and possible therapeutic modalities is undertaken. PMID- 1292410 TI - The challenge of health care reform. PMID- 1292411 TI - Don't forget GratefulMed when conducting literature searches. PMID- 1292409 TI - Howard Eddey. PMID- 1292412 TI - Sexual dysfunction in the male end stage renal disease patient. AB - This article reviews the anatomy and physiology of the male reproductive system and pathophysiology attributed to chronic renal disease. Clinical evaluation strategies are outlined and treatment modalities explained. The role of the nephrology nurse is outlined as a patient advocate and advisor. PMID- 1292413 TI - Microwave warming of peritoneal dialysis fluid. AB - A nursing research study was undertaken to determine whether biochemical composition of peritoneal dialysate fluid was altered with microwave heating and whether the external bag temperature of the heated dialysate was a reliable reflection of the actual fluid temperature. No significant laboratory changes were found in the control, heated, or superheated solutions. By closely following established time frames for specific bag solution volume, agitation of fluid prior to instillation, and external temperature check with specific minimum and maximum acceptable temperatures, peritoneal dialysate can be microwaved and used safely. PMID- 1292414 TI - Clinical experience with erythropoietin in continuous ambulatory peritoneal dialysis. AB - The purpose of this project was to determine a safe and effective Epogen (EPO) subcutaneous administration schedule for patients who were on continuous ambulatory peritoneal dialysis. To comply with the manufacturer's recommendation to enter a vial only once, a dosing regimen had to be established that used a standard dose of 2,000 or 4,000 units. The goal was to determine the frequency of administration that would achieve and maintain the target hematocrit. Twenty-six patients participated. The starting dose of 4,000 units was administered either two or three times per week. An average 8.3% point increase in hematocrit was seen in 8 weeks. When the target hematocrit of 33% to 35% was reached, the dose and or frequency of administration was decreased. Maintenance doses were established at 2,000 or 4,000 units weekly or biweekly. We were able to meet and maintain the target hematocrit by using 2,000 or 4,000 units per dose and adjusting the frequency. PMID- 1292415 TI - Work stress, burnout, and sense of coherence among dialysis nurses. AB - The overall goal of this study was to examine the relationship among work stressors, burnout, and sense of coherence (SOC) in dialysis nurses. Two hundred thirty-eight registered nurses from 56 dialysis units completed a demographic data form, the Nursing Stress Scale, the Maslach Burnout Inventory, and Antonovsky's Sense of Coherence Scale. The results indicated that work load was the major contributing factor to both overall stress and burnout. Understanding the stressors that affect responses to the work environment will allow for successful interventions to alter the risk of exhaustion and burnout. PMID- 1292416 TI - Bartter's syndrome: a chronic electrolyte losing syndrome. AB - Bartter's Syndrome is a chronic electrolyte losing syndrome with symptoms and abnormalities that form an organized framework in which to study clinical effects of chronic electrolyte disturbances. Bartter's Syndrome has received minimal attention in continuing education journals. The purpose of this article is to define Bartter's Syndrome, present the historical significance, pathophysiology and clinical signs and symptoms. Selected results of a case study, with specific clearance studies and nursing implications, designed to diagnose and treat this rare renal tubular dysfunction will also be presented. PMID- 1292417 TI - Differences in immunosuppressant agents. PMID- 1292418 TI - Positive impact of home hemodialysis. AB - The intended patient outcomes have been achieved. Home hemodialysis has improved the quality of life for this entire family. Continuous support is necessary to help this family maintain an acceptable lifestyle. This remains a primary goal of care. The nephrology nurse proved to be the key to this successful home hemodialysis experience. Appropriate training coupled with frequent communication and encouragement resulted in a positive patient and family outcome. PMID- 1292419 TI - Case management of the anemic patient. Epoetin alfa: focus on sexual dysfunction. AB - Sexual dysfunction is a common problem for patients with ESRD. This article discusses the nature of the problem, along with the improvement in sexual function that has been noted after beginning therapy with Epoetin alfa. The assessment and management of patients with sexual dysfunction are described, and the role of the nurse is emphasized. PMID- 1292420 TI - Calcitriol injection for the management of renal osteodystrophy. AB - The introduction of synthetically produced calcitriol in the early 1970s was an important contribution to the prevention and treatment of renal bone disease. However, despite the efficacy and the availability of oral calcitriol many dialysis patients continued to develop secondary hyperparathyroidism (Norris, 1991). Effective treatment was often impossible in patients with osteitis fibrosa because even low oral doses of calcitriol could cause hypercalcemia (Andress, Norris, Coburn, Slatopolsky, & Sherrad, 1989). From 1981 to the present, numerous studies have been conducted that have demonstrated intravenous calcitriol as being more effective and having several advantages over the oral route of administration, particularly in patients with poor compliance and those with a tendency to develop hypercalcemia. PMID- 1292421 TI - The biomedical literature on central Africa 1880-1991. Preliminary observations. PMID- 1292423 TI - Screening for Trypanosoma brucei gambiense antibodies with the Indirect Fluorescent Antibody Test (IFAT). Effect of age and previous treatment. AB - This paper reports on some of the findings of a longitudinal multi-round investigation into the predictive power of early signs and symptoms of human African trypanosomiasis caused by T.b. gambiense, in the Rural Health Zone of Kasongo (Maniema, Zaire). It assesses the importance of the effect of age and a history of previously treated sleeping sickness on serological positivity as measured by the Indirect Fluorescent Antibody Test (IFAT), used as a screening test. The impact of including age and a history of previous sleeping sickness as part of the screening process is discussed in terms of sensitivity and positive predictive value. Including weak serological positivity among the screening criteria does not appear to improve the sensitivity of the IFAT test in this setting. PMID- 1292422 TI - [Efficacy of radical treatment with halofantrine on the prevention of imported Plasmodium falciparum malaria]. AB - We carried out in 1989 a non randomized comparative study in French army units which had been in Central Africa (Central African Republic and Gabon) for 4 months, in order to compare in 758 men on return from malaria areas the usual strategy of chemoprophylaxis with chloroquine and a radical cure by halofantrine (Halfan). Chloroquine was taken by 278 men (100 mg daily for 6 weeks after their return to France); the other 480 men were given two doses of 1,500 mg halofantrine on the third and on the tenth day after their return to France. In Africa both of the units were on chloroquine prophylaxis (100 mg daily for 4 months). The Plasmodium falciparum attack rates were, during a period of 5 months after the return to France, 0.2% in the halofantrine group (1/480) and 4.7% (13/228) in the chloroquine group (P < 10(-4)). The radical cure by halofantrine was more effective than chloroquine prophylaxis in preventing falciparum malaria on return from malaria areas. PMID- 1292424 TI - Evaluation of the cryptococcal antigen test as a diagnostic tool of AIDS associated cryptococcosis in Rwanda. AB - To evaluate the latex test, two different retrospective studies were undertaken. A positive culture for Cr. neoformans was used as the golden standard of active cryptococcal infection. 439 sera selected at random sent to the NSP laboratory for screening of HIV antibody were tested as well as--71 CSF from patients with meningeal symptoms sent to the laboratory of the Centre Hospitalier de Kigali. In total, two discrepancies were found: two CSF samples from ancient cases of cryptococcosis under treatment were positive with the latex test and negative by culture. If it stands to reason that the antigen test cannot differentiate between active and inactive cryptococcal diseases, the persistence of small amounts of soluble antigens in a CSF implies that the patient must remain under surveillance, a relapse being very frequent in AIDS patients. As a conclusion, the latex test is a fast, easy to perform and quite reliable test for the diagnosis of cryptococcosis. PMID- 1292425 TI - [Seroepidemiological study of toxoplasmosis in Libreville, Gabon]. AB - A sero-epidemiological survey of toxoplasmosis has been carried out in 1178 subjects residing in urban and suburban areas of Libreville, Gabon. Two techniques were used: Pastorex toxo of the Institut Pasteur and ISAGA of bioMerieux. The acquisition of antibodies occurs at an early age, from the age of six months on. After the age of 15 years, the age of procreation, the prevalence is 68%. Between the ages of 15 and 19 years, 19% have IgM. The risk for toxoplasmosis acquired during pregnancy is not to be neglected. It decreases between the ages of 20 and 30 years. The most probable source of contamination is the reservoir from the soil. No difference between the sexes was observed. PMID- 1292426 TI - [High prevalence of konzo associated with a food shortage crisis in the Bandundu region of zaire]. AB - Konzo is a form of spastic paraparesis reported from several rural areas in Sub Saharan Africa. It has been attributed to cyanide exposure from exclusive consumption of insufficiently processed bitter cassava roots. We have tested this attribution in a community based epidemiological survey in an area of Bandundu region in Zaire composed of two agro-ecological zones: savanna and forest. In the savanna area with poor soils we found 78 konzo cases in 1,936 inhabitants, a prevalence of 4%; but in the forest area only 9 cases in 5,531 inhabitants (0.2%). This geographical distribution as well as the temporal distribution coincide with frequent short-soaking of cassava roots (only one night) induced by an agro-ecological crisis. High levels of blood cyanide, mean 13.3 mumol/l (range: 0.1-76.3) and serum thiocyanate, mean (+/- SD) 401 (+/- 126) mumol/l, in a sample of 18 subjects from the savanna area confirm high cyanide exposure in this population with high prevalence of konzo. Prevention of konzo in Zaire is possible by promotion of sufficient soaking of cassava with strict adherence to traditional three nights soaking and the use of completely dry flour. PMID- 1292427 TI - [Population dynamics and infestation of Bulinus truncatus and Bulinus forskalii by schistosomal larvae in the Sudan-Sahelian zone of Cameroon]. AB - The evolution of the population densities of Bulinus truncatus and Bulinus forskalii has been studied during 18 months in a number of sites of the Sudan Sahelian zone of Cameroon, in relation to certain environmental factors. Only the altitude of the water in the sites has an influence on the density of the snails. The populations of B. truncatus present a greater proportion of young molluscs during the entire year, with the exception of the last months of the dry season. The population dynamics of B. forskalii varies depending on whether the environment is temporarily stagnant, temporarily running or stable. The proportions of B. truncatus and B. forskalii that emit cercariae of schistosomes are 1.2% and 0.8% respectively. Study of the adult worms obtained after infestation of the laboratory mammals show that B. truncatus emits cercariae of Schistosoma haematobium at the end of the dry season and at the beginning of the rainy season. We have not been able to identify precisely the cercariae emitted by B. forskalii, which raises the necessity of further systematic studies being carried out on the schistosomes of Cameroon. PMID- 1292428 TI - [Typology and performance of first-referral hospitals in sub-saharan Africa]. AB - This descriptive study provides a typology of first referral level hospitals in sub-Saharan Africa. Data are provided on 88 mainly non-governmental hospitals in 25 African countries. They were obtained through a mail survey. The first aspect discussed is the place of the hospital within the spatial organization of the health care district: population served and other health units. This makes it possible to classify the hospitals in three groups. The analysis of the role of the hospital in the management of the district and the support of the peripheral network is based on information about the formal relations of authority, the participation of the hospital in training and supervision, in provision of drugs and in the financial management of the district. This is followed by a description of the human and other resources available in the hospitals, the type and organization of care provided, as well as the performances in terms of outpatient care, inpatient care and technical interventions. Finally, the available information on expenditure and sources of financing is presented. PMID- 1292429 TI - Bone tissue growth enhancement by calcium phosphate coatings on porous titanium alloys: the effect of shielding metal dissolution product. AB - The possible mechanism of minimization of prosthesis-derived bone growth inhibitors by shielding of the metal and the reduction, if not elimination, of the associated metal dissolution was investigated. Titanium, aluminium and vanadium release rates were determined in vitro for Ti alloy specimens both with and without a calcium phosphate coating. Ti orderly oriented wire mesh (OOWM) porous coatings on Ti-6Al-4V substrates were used as the metal specimens. Half of the specimens were coated with a 75 microns calcium phosphate ceramic (CPC coating). Seven reference (OOWM) and seven coated (OOWM-CPC) specimens were immersed and placed along with seven control solutions for various periods in an incubator maintained at 37 degrees C and 5% CO2 - air atmosphere. Whereas the reference solutions showed a Ti release increasing as a function of time, the solutions that had the CPC-coated specimens contained no measurable amounts of titanium. The Al in solution around the CPC-coated specimens was significantly greater than the concentration around non-coated specimens. The Al, however, did not increase significantly with time, at least up to 4 wk immersion. The ceramic coating had a small beneficial effect on V concentration. In the absence of a significant adverse effect of Ti on local bone tissue formation, we focus on the Al data of our study. The possible adverse effect of this element is well documented. The calcium phosphate coating produced a significant increase of biological fixation, yet at the same time a greater Al release into solution, calling into question the significance of CPC coating in shielding adverse metal passive dissolution to explain enhanced bone growth [corrected]. PMID- 1292430 TI - Gene patenting. Top HHS lawyer seeks to block NIH. PMID- 1292431 TI - Using theory and basic research to target primary prevention programs: recent developments and future prospects. AB - This paper is concerned with recent attempts within the field of primary prevention to use theory and basic research to develop intervention programs. It starts by reviewing a number of recent large scale studies based upon the dominant theoretical perspective within this field--the social influences model. It argues that the results of such evaluations suggest that a 'universal' prevention strategy (i.e. one aimed in an undifferentiated manner at all individuals within a given population) is out of touch with our current knowledge concerning the etiological processes underlying substance use and misuse. As an alternative, it is suggested that prevention programs be developed according to a number of 'specific' strategies (i.e. ones targeted at vulnerable subgroups within larger populations). The rationale underlying this approach, as well as a number of theoretical models upon which such interventions might be developed, is then outlined. PMID- 1292432 TI - Alcohol and the skin. AB - The cutaneous stigmata of chronic alcoholic liver disease have been well recognised since the nineteenth century. However, it is now clear that the skin may be affected as an early feature of alcohol misuse. In particular, psoriasis, discoid eczema and superficial infections are more common in heavy drinkers. Awareness of these early associations can alert physicians to patients at risk of future complications of alcoholism. Great advances have been made in the understanding of the physiological and pathological effects of ethanol. The implications of these changes in the skin are discussed with reference to both the new and established cutaneous signs of alcohol misuse. PMID- 1292433 TI - Platelet paroxetine binding in alcoholics. AB - Platelet paroxetine binding was analysed in 24 abstinent alcoholics and 18 control persons. The alcoholics had significantly more binding sites than the control persons. Most of the alcoholics showed affective symptoms and the increased platelet paroxetine binding was predominantly observed among those who had the lowest Newcastle score, indicating the presence of non-endogenous depression. PMID- 1292434 TI - Reduced spinal and femoral bone mass and deranged bone mineral metabolism in chronic alcoholics. AB - Prevalence and factors which may influence the development of osteoporosis have been assessed in 32 chronic alcoholic males by measuring the bone mineral density (BMD) of the lumbar spine and femoral neck by dual photon absorptiometry. Serum bone Gla-protein, as an index of bone formation, 25-hydroxyvitamin D, testosterone and cortisol levels were also measured. Eleven patients (34%) had osteoporosis. In seven the lumbar BMD was below the fracture threshold. Lumbar and femoral neck age-matched BMD were below mean normal values in 20 and in 23 patients, respectively. Moreover, the age-matched BMD was significantly lower in the femoral neck (91.7 +/- 14.4%) than in the lumbar spine (100.1 +/- 17.1%) (P < 0.001). Duration of alcoholism was significantly higher in patients with age matched BMD below 100% than in those with age-matched BMD above 100%. Bone GLA protein and 25- hydroxyvitamin D were below normal levels in 67% and 56% of patients, respectively. Serum testosterone was normal in all but two patients, and cortisol was within normal values in all patients tested. In addition a direct correlation was found between the days of abstinence before the study and serum levels of bone GLA-protein (r = 0.64, P < 0.001). In conclusion, chronic alcoholics frequently have bone loss of the lumbar spine and femoral neck related with the duration of alcohol intake. The correlation between bone-GLA protein levels and the days of abstinence suggests that alcohol directly depresses bone formation. Likewise, the low levels of vitamin D also support that this deficiency may contribute to the development of osteopenia in chronic alcoholism. PMID- 1292435 TI - Acute inhibition of lipid transport in rat intestinal lymph by ethanol administration. AB - To observe the effect of acute ethanol ingestion on stable lipid transport in intestinal lymph, three groups of mesenteric lymph fistula rats were prepared. In group A rats, lipid emulsion containing 120 mumol/hr of oleate (control meal) was infused intraduodenally for 8 hr. Group B rats were infused with another lipid emulsion, which had the same basic composition as the control meal but included 0.75 g/kg body weight/hr of ethanol (alcohol meal), for 8 hr. In group C, rats were infused with the control meal for the first 4 hr, then with the alcohol meal for the next 4 hr. Lymph flow increased just after the infusion of ethanol, that is, lymph flow in group B was significantly higher than that of group A at 1 and 2 hr, and lymph flow in group C was significantly higher than that of group A at 5 hr. In group A, lymphatic triglyceride (TG) output reached a plateau of more than 30 mumol/hr after 3-hr infusion. TG output in group B was significantly lower than that in group A from 2 hr to 8 hr and was two-thirds that of group A at the plateau level. In group C, TG output was the same as in group A until 5 hr, but decreased to two-thirds of that in group A at 6 hr, 2 hr after replacing the control meal with the alcohol meal. Lymphatic phospholipid output exhibited a tendency similar to that of TG output. Comparisons of group A vs. B and A vs. C clearly demonstrated an inhibitory effect of ethanol on stable lipid transport in intestinal lymph. A 2-hr infusion was enough for ethanol to exhibit its inhibitory effect. In conclusion, stable lymphatic transport of intestinal absorbed lipid was suppressed by acute ethanol ingestion. PMID- 1292436 TI - Imidazole dipeptides in experimental alcohol-induced myopathy. AB - Rats were chronically fed a nutritionally complete liquid diet containing 35% of total calories as either ethanol, or (for the controls) an isocaloric amount of glucose. After 6 weeks of treatment, the feeding regime induced skeletal muscle myopathy as characterised by reductions in muscle weight and RNA content. Ethanol preferentially affected the metabolically glycolytic plantaris (Type II fibre predominant) muscle of the rat, compared with the metabolically oxidative soleus (Type I fibre-predominant). The changes in the plantaris were associated with increases in the concentration (mumol per g wet weight) of anserine (18%) and carnosine (50%). No significant changes were seen for the concentrations of either anserine or carnosine in the soleus muscle. The total contents (mumol per muscle) of carnosine and anserine in the plantaris were not significantly altered by ethanol treatment, though a significant decrease in anserine content (30%) occurred in the soleus. It is concluded that reductions in imidazole dipeptide content, considered to be antioxidants and/or intracellular buffering agents, are not mediating factors in the development of chronic experimental myopathy. PMID- 1292437 TI - Kinetics of ethanol and methanol in alcoholics during detoxification. AB - We investigated the kinetics of ethanol and methanol in 20 dependent alcoholics (16 men and four women) during the first 24 hr after admission to hospital for detoxification. The blood-ethanol concentration (BEC) on admission ranged from 238 to 489 mg/dl (mean 386 mg/dl). The mean rate of ethanol disappearance from the blood was 23 mg/dl/hr with a spread from 13 to 36 mg/dl/hr. The concentrations of methanol in blood at the start of detoxification ranged from 0.16 to 2.8 mg/dl (mean 1.15 mg/dl) and these levels remained more or less unchanged until the BEC had dropped below 30 mg/dl. The concentrations of ethanol and methanol in blood at the start of detoxification were not correlated (r = 0.032, P > 0.05). The results of this study do not support the notion that the metabolism of methanol in chronic alcoholics proceeds independently of the prevailing BEC. We found a three-fold difference in the rate of disappearance of ethanol from blood in alcohol-dependent subjects. PMID- 1292438 TI - A randomized study of long-term out-patient treatment in alcoholics. Psychiatric treatment versus multimodal behavioural therapy, during 1 versus 2 years of treatment. AB - Seventy-two alcoholic patients (60 men and 12 women) were randomized into four groups who received psychiatric treatment (PT) or multimodal behavioural therapy (MBT), for either 1 or 2 years. PT was based on psychodynamic principles, and MBT is a cognitive-behavioural treatment. The patients accepting treatment had a mean age of 37 +/- 9 years, and they were socially stable. There was no difference in attrition rate (35%) in relation to therapy and length of treatment. The rate of favourable drinking outcome during the third year was similar in all four alternatives, at 40-44%. A favourable drinking outcome was predicted by a better initial psychic status and few psychiatric symptoms at intake. In PT patients a favourable outcome was more strongly related to a better psychic status than in MBT patients (P = 0.58). The mean number of sessions, 23, did not differ in relation to outcome. The main conclusion from this study is that there were only small and inconclusive differences between the therapies of different types and different duration. PMID- 1292439 TI - Physician's information about alcohol problems at hospitalisation of alcohol misusers. AB - Information was gathered on recognition and treatment of alcohol problems in the primary and secondary health sectors, the latter represented by a department of hepatology. The general practitioner finds in most cases (18/26, 69%) that it is relevant to advise about a patient's alcohol misuse on admission forms when the patient previously has been discharged from another department with this diagnosis. However, if the patient has not previously been hospitalised due to alcohol misuse, information on the diagnosis is only rarely (30/114, 26%) available. This difference is highly significant (P = 0.0001). The case-recording hospital physician at admission recognises 73% of alcohol misusers who are admitted with a non-alcohol-related diagnosis. When the patient had been evaluated by both the admitting physician and the case-recording hospital physician, information on the alcohol problem occurred significantly less often in female compared to male patients (75% vs. 94%; P < 0.002). Only 42 of 208 (20%) of alcohol misusers were under treatment with thiamine/B-vitamins and/or disulfiram before admission. There was a significant difference (P < 0.003) as to whether the patient was treated when the general practitioner wrote alcohol misuse on the admission form and when he did not (37% vs. 10%). At admission, treatment was begun in 54%, and by the discharge 78% were under treatment. Further quality assurance in the diagnosis and treatment of patients with alcohol problems is needed. PMID- 1292440 TI - A descriptive study of alcohol-dependent women attending Alcoholics Anonymous, a regional council on alcoholism and an alcohol treatment unit. AB - A total of 86 women, attending three different agencies, were interviewed on their help-seeking behaviours for problem drinking. Each agency represented a different type of help available in the community. Self-help was represented by Alcoholics Anonymous; the non-statutory sector by a regional council on alcoholism's offices; and the statutory sector by an alcohol treatment unit's out patient department. Differences between the groups in terms of demography and drinking history are explored in this paper. It was found that the regional council group resembled the female problem drinkers in other alcohol treatment agencies in terms of alcohol dependency, pattern of alcohol consumption and drinking styles, but differed in age and abstinence behaviour. PMID- 1292441 TI - Old and new MMPI-derived scales and the short-MAST as screening tools for alcohol disorder. AB - Ten previously published and two new MMPI-derived scales were compared with the short-form of the Michigan Alcohol Screening Test (SMAST-13) in terms of sensitivity and specificity at detecting alcohol disorder in a study of 100 alcohol out-patients, 100 mental health out-patients, and 100 college students. The SMAST-13 and the new MMPI-derived alcoholism scales performed best at detecting alcohol disorder on multiple criteria including the standard contingency table, relative efficiency, and receiver operator characteristic analyses. These conclusions, were found to be robust in separate analyses for males and females. PMID- 1292442 TI - Operational definitions of alcohol dependence and associated factor structures. AB - This paper examines the impact of three different operational definitions of alcohol dependence on analyses of the factor structure of that concept. Data came from a sample of 219 men interviewed while in treatment for alcohol problems. The first operational definition was created with 20 items previously used in the literature and which are thought to represent the elements of dependence in the DSM-III-R criteria. In the second operational definition, the 20 items composing the first definition are combined under each of nine elements approximating the DSM-III-R criteria and thus analyzed. Finally, in the third operational definition, rather than using traditional items, the elements of the syndrome are defined by new items with wording close to that found in the DSM-III-R criteria. Results show variations ranging from a dual factor to a five-factor structure depending on the operational definition being analyzed. PMID- 1292443 TI - Alcoholism flows from the pleasures of the many, not the sins of the few. PMID- 1292444 TI - Artificial intelligence in automated classification of rat vaginal smear cells. AB - Microscopic examination of vaginal smears has been used routinely to determine the stage of the estrous cycle of female rats in reproductive research. The stage of the estrous cycle is based on relative counts of nucleated epithelial cells, cornified epithelial cells and leukocytes. The purpose of this project was to explore automation of vaginal smear analysis using image processing and artificial intelligence techniques. A fully connected back-propagation neural network was used to locate all potential objects in a digitized scene. A unique algorithm was then employed to center a subsequent sampling box to collect pixel intensity values from the red and green components of each image. A final neural network was used in the classification of cell type. Neural networks were used because of their ability to generalize among input patterns and to tolerate extraneous noise due to variations in staining artifacts and aberrant illumination of the microscope field. This preliminary cell diagnosing system not only provides the basis for the fully automated system but also provides a method by which many other cytologic image processing problems can be automated. PMID- 1292445 TI - Bayesian belief networks in quantitative histopathology. AB - Bayesian belief networks have a dynamic range and numeric response characteristics that make them uniquely suitable for descriptive classification schemes. Features showing considerable overlap of tolerance regions may be used, in a cumulative manner, to derive unequivocal classification decisions. The numeric response characteristics of Bayesian belief networks are analyzed, and their application as control modules in automated scene segmentation in histopathology is demonstrated. PMID- 1292446 TI - Comparison of nuclear shape in aspirated and histologic specimens of prostatic carcinoma. AB - Nuclear shape analysis of histologic sections of operative specimens has separated patients with clinically localized prostatic carcinoma with good and poor prognoses. In order to become more useful clinically, nuclear shape should be evaluable preoperatively but is distorted by core biopsy. We used nuclear morphometry to compare histologic and cytologic specimens obtained from 20 patients who underwent radical prostatectomy for clinically localized prostatic carcinoma. Neoplastic nuclei from cytologic aspirates prepared by the Papanicolaou and Diff-Quik techniques and standard histologic sections stained with hematoxylin and eosin were digitized. Air-dried nuclei of the Diff-Quik preparation had a nuclear area of 104.2 microns 2 +/- 28.2 SD. These nuclei were nearly twice as large (paired t test, P < .001) as in the Papanicolaou (55.6 +/- 13.0 microns 2) and histologic (55.8 +/- 12.7 microns 2) preparations. However, nuclear shape was not affected. Nuclear roundness factor (deviation from circularity) and boundary curvature were similar (paired t tests, P > .05). All nuclear shape descriptors of cytologic smears fell within intraobserver variations of measurements in histologic sections. Nuclear shape is not altered in Papanicolaou- and Diff-Quik-stained cytologic specimens and should be tested for preoperative assessment of outcome in clinically localized prostatic carcinoma. PMID- 1292447 TI - Syntactic structure analysis of the arrangement of nuclei in dysplastic epithelium of colorectal adenomatous polyps. AB - In search of new objective classifiers of the degree of dysplasia in colorectal adenomatous polyps, we conducted syntactic structure analysis on hematoxylin eosin-stained tissue sections of 59 colorectal adenomas. The adenomas were subjectively graded as showing mild (n = 20), moderate (n = 20) or severe (n = 19) dysplasia in a double-blind examination by two pathologists. Using an interactive video-overlay measuring system, a minimum spanning tree was computed in 10 fields per specimen according to a strict measurement protocol. From each minimum spanning tree, such features as total line length, length of line segments, total number of points and number of points with one, two, three or four neighbors were derived. Simple descriptive statistics of these minimum spanning tree features were used to analyze differences between the three grades of dysplasia. Univariate analysis indicated that most of the variables used were suitable for discriminating between mild and moderate as well as between mild and severe grades of dysplasia. Only median minimum line length also showed significant differences between moderate and severe dysplasia. By means of a jackknifed stepwise discriminant analysis, an overall correct classification of mild versus moderate and severe dysplasia of 81.4% was achieved. It is concluded that syntactic structure analysis may have additional value in describing, in an objective and rapid way, the morphologic changes of dysplasia in colorectal adenomatous polyps. PMID- 1292448 TI - Interactions between dental amalgams and the oral environment. AB - Dental amalgam fillings interact in a complex way with the environment in the oral cavity as they are subjected to chemical, biological, mechanical, and thermal forces. These forces change the restoration's appearance and properties, while metal ions, amalgam debris, non-metallic corrosion products, and mercury vapor are released into the oral cavity. The phenomena and conditions that affect the amalgam/environment interaction include the chemistry and biochemistry of the environment, formation of biofilms on the amalgam surfaces, existence of localized corrosion cells, galvanic contacts with other metallic restorations, abrasion during mastication, and synergistic effects of the different forces. Corrosion processes result in a degradation of the functional amalgam properties, while tarnishing reactions cause discoloration. Corrosion degradation of amalgam fillings is due mainly to localized corrosion cells in pores and crevices. Corrosion on occlusal surfaces is accelerated by abrasion during mastication, which removes the protective surface films. The average total amounts of metal species, including mercury, released per day in vivo from a restoration have not been determined. Much of the reported indirect evidence for high mercury release rates is either unreliable or controversial. A more detailed investigation is needed and will require the development of more sophisticated techniques of sampling in vivo, as well as both experimental and theoretical modeling in vitro. PMID- 1292449 TI - Side-effects: mercury contribution to body burden from dental amalgam. AB - The purpose of this paper is to examine and report on studies that relate mercury levels in human tissues to the presence of dental amalgams, giving special attention to autopsy studies. Until recently, there have been few published studies examining the relationship between dental amalgams and tissue mercury levels. Improved and highly sensitive tissue analysis techniques have made it possible to measure elements in the concentration range of parts per billion. The fact that mercury can be absorbed and reach toxic levels in human tissues makes any and all exposure to that element of scientific interest. Dental amalgams have long been believed to be of little significance as contributors to the overall body burden of mercury, because the elemental form of mercury is rapidly consumed in the setting reaction of the restoration. Studies showing measurable elemental mercury vapor release from dental amalgams have raised renewed concern about amalgam safety. Mercury vapor absorption occurs through the lungs, with about 80% of the inhaled vapor being absorbed by the lungs and rapidly entering the bloodstream. Following distribution by blood circulation, mercury can enter and remain in certain tissues for longer periods of time, since the half-life of excretion is prolonged. Two of the primary target organs of concern are the central nervous system and kidneys. PMID- 1292450 TI - Teratological aspects of dental amalgam. AB - The teratogenic effect is determined by four factors: (1) the agent, (2) the dose, (3) the stage of embryonic development, and (4) the genetic constitution of the embryo. The first two factors are of particular interest and warrant further comment. It should be emphasized that the mercury released from dental amalgam is mainly metallic mercury vapor. The dose of mercury vapor from dental amalgam fillings in the order of 5 micrograms/day is very low compared with the doses in a teratological study and is not likely to exceed the threshold necessary for a teratogenic effect to occur. The concentration of the teratogen at the target tissue is determined not only by the degree of placental transfer but also by other factors, such as the distribution within the maternal organism, the affinity to the fetal liver and blood, the hematocrit value, and the passage through the ductus venosus. These factors might help to explain toxicological mechanisms and species differences and have to be considered if the results of animal experiments are to be extrapolated to human conditions. Neither epidemiological data nor animal experimental data indicate that the release of metallic mercury vapor from dental amalgam therapy should cause teratogenic effects. A comparison with the incorporation of the fetotoxic methyl mercury might be justified. PMID- 1292451 TI - Oral mucosa and skin reactions related to amalgam. AB - Documented cases of oral mucosa and skin affections related to amalgam restorations are rare, although the exact incidence is unknown. Lesions of the oral mucosa may be due to specific immunologic or non-specific toxic reactions toward products generated from restorations. The immunologic reaction most probably involved in mucosal affections related to amalgam is the delayed or cell mediated (type IV) reaction. Such reactions are seen in contact allergy, and the term "contact lesions of the oral mucosa" has been used. There is a much lower tendency of sensitization through mucous membranes than through skin, and it is questionable whether mercury released from amalgam restorations is able to sensitize a patient. A chronic toxic reaction may be established due to repeated or constant influence to toxic agents in low concentrations over long periods. Such reactions are most frequently localized to the contact zone with the toxic agent. Chronic toxic reactions may possibly be seen in areas of the oral mucosa in direct contact with amalgam fillings. Since the clinical features of these lesions do not differ from those of lesions due to contact hypersensitivity, the diagnosis is obtained by exclusion based on a negative patch test. PMID- 1292452 TI - Dental amalgam--environmental aspects. AB - Increasing knowledge about the risk of toxic effects caused by anthropogenic mercury accumulation in ecosystems has resulted in a growing pressure for reduction of the discharge of mercury waste. Consequently, the mercury waste problems of dental clinics have been given increased attention, and restrictions on handling and discharge of contaminated waste have been established in several countries. Major amalgam particles from trituration surplus of those produced during the carving and burnishing of new amalgam restorations are generally collected in coarse filters and sold for refinement. Minor amalgam particles released by production of new fillings or by removal of old restorations partly sediment in tubes and drains. The remaining particles are carried with the waste water stream to the local purifying plant. In Scandinavia, the industrial discharge of mercury-contaminated waste water has been reduced to a minimum. According to recent investigations, dental clinics appear to be responsible for the major amount of mercury collected in the sludge generated in purifying plants. If threshold values for heavy metal content, including mercury, are exceeded, the sludge is not allowed to be recycled as fertilizer. Installation of an approved amalgam-separating apparatus in dental clinics is now mandatory in several countries--for example, Switzerland, Germany, Sweden, and Denmark. Approval of amalgam separators is based on national testing programs, including clinical or laboratory tests demanding 95-99% separating efficiency. PMID- 1292453 TI - Documented clinical side-effects to dental amalgam. AB - Since all dental restorative materials are foreign substances, their potential for producing adverse health effects is determined by their relative toxicity and bioavailability, as well as by host susceptibility. Adverse health effects to dental restoratives may be local in the oral cavity or systemic, depending on the ability of released components to enter the body and, if so, on their rate of absorption. The medical scientific community is now in general agreement that patients with dental amalgam fillings are chronically exposed to mercury, that the average daily absorption of mercury from dental amalgam is from 3 to 17 micrograms per day, and that the amalgam mercury absorption averages 1.25-6.5 times the average mercury absorption from dietary sources (World Health Organization, 1991). The health significance of this chronic mercury exposure is now being investigated by several medical research groups. PMID- 1292454 TI - Dental amalgam and mercury vapor release. AB - Dental diseases are among the most common ailments, and dentists in the United States spend over 50% of their time in dental practice rebuilding carious, malformed, and traumatically injured teeth. It is logical, therefore, that the majority of the dental school curriculum is devoted to the diagnosis, prevention, and treatment of teeth with anomalies. Dentists have several choices of materials they can use to accomplish the task of rebuilding teeth. Besides amalgam, they have ceramic materials, resin composites, base-metal and noble casting alloys, and glass-ionomer cements to use to restore the posterior dentition. Each of these restorative materials has advantages and disadvantages, and the clinical judgment as to when a particular material should be used is given a high priority in dental education. Amalgam is the most widely used of these restorative materials, with 92% of dentists listing it as the material of choice in the posterior of the mouth (Clinical Research Associates, 1990). Dentists have been placing amalgams for over 150 years in the US. They placed 150 million last year, which represents over 75 tons of amalgam alloy. The reasons that dentists use this restorative material so frequently are its durability, ease of manipulation, and low cost. Numerous clinical studies have been conducted on the serviceability of amalgam. Most of these have been on the old, low-copper alloys, and results indicate that they last from 8 to 15 years (Bailit et al., 1979; Osborne et al., 1980; Qvist et al., 1986). In the past 20 years, vast improvements have been made in amalgams with the development of the high-copper systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292455 TI - Statement: effects and side-effects of dental restorative materials. PMID- 1292456 TI - Toxicology versus allergy in restorative dentistry. AB - The frequency of side-effects among dental patients is very low and is seen mostly as mild allergic reactions. Among the dental staff, contact allergic eczema is occasionally seen, induced by certain metals and various organic materials. PMID- 1292457 TI - Principles of risk assessment. AB - This review discusses the basic principles of risk assessment as used in general toxicology and in monitoring side-effects of therapeutic treatments. It also outlines how these principles may apply to assessment of biological reactions to dental restorative materials. Mercury exposure from amalgam fillings is used as an example. The calculations performed are intended only as illustrations, and many other factors must be taken into account. Thus, the calculations are not intended as the last word in risk assessment of amalgam fillings. PMID- 1292458 TI - Casting alloys: the materials and "The Clinical Effects". PMID- 1292459 TI - Biodegradation of restorative metallic systems. AB - Metallic materials utilized for the construction of intra-oral and implant dental restorations include a wide range of relatively pure metals and multicomponent alloys. Basic corrosion and biodegradation properties of these alloys have been studied by both in vitro and in vivo techniques. These property characteristics have been shown to be dependent on composition and metallurgical state, combinations within a construct, surface conditions, mechanical aspects of function, and the local and systemic host environment. The susceptibility of these metallic materials to various forms of biodegradation will be presented, with emphasis on corrosion. PMID- 1292460 TI - Casting alloys: side-effects. AB - Side-effects from dental materials are a minor problem, but should be recognized. In recent questionnaire surveys about side-effects, the incidence was estimated to be 1:300 in periodontics and 1:2600 in pedodontics. None of these reactions was related to dental casting alloys. In prosthodontics, the incidence was calculated to be about 1:400, and about 27% were related to base-metal alloys for removable partial dentures (cobalt, chromium, nickel) and to noble/gold-based alloys for porcelain-fused-to-metal restorations. The complaints consisted of intra-oral reactions (such as redness, swelling, and pain of the oral mucosa and lips), oral/gingival lichenoid reactions, and a few instances of systemic reactions. In orthodontics, the incidence was 1:100, and most reactions (85%) were related to metal parts of the extra-oral anchorage devices. Even though the extensive use of base-metal alloys has been of major concern to the dental profession, relatively few case reports substantiate this concern. Allergy to gold-based dental restorations has been more commonly reported. Palladium-based alloys have been associated with several cases of stomatitis and oral lichenoid reactions. Palladium allergy seems to occur mainly in patients who are very sensitive to nickel. All casting alloys, except titanium, seem to have a potential for eliciting adverse reactions in individual hypersensitive patients. Tolerance induction may be a possible benefit of the use of intra-orally placed alloys. In non-sensitized individuals, oral antigenic contacts to nickel and chromium may induce tolerance rather than sensitization. A variety of systemic diseases and reactions has been claimed to be caused by dental materials. The claims are generally poorly documented. PMID- 1292461 TI - Future needs for dental restorative materials. AB - While the population of the United States increases from 250 to 310 million people, the number in older age groups will increase dramatically from 28 million to about 64 million. Tooth retention has improved remarkably in the 65-74 age groups, from 7.4 in 1962 to 17.9 in 1986. While younger age groups will require less treatment due to decline in dental caries, older age groups appear to require more treatment than did similar age cohorts in previous generations. Hence, the need for restorative procedures by the United States population will be on an upward trend for the next decade or two. PMID- 1292462 TI - Dental composites/glass ionomers: the materials. AB - Most commercial dental composites contain liquid dimethacrylate monomers (including BIS-GMA or variations of it) and silica-containing compositions as inorganic reinforcing filler particles coated with methacrylate-functional silane coupling agents to bond the resin to the filler. They also contain initiators, accelerators, photo-initiators, photosensitizers, polymerization inhibitors, and UV absorbers. Durability is a major problem with posterior composites. The typical life-span of posterior composites is from three to 10 years, with large fillings usually fewer than five years. Polymerization shrinkage and inadequate adhesion to cavity walls are remaining problems. Some pulp irritation can occur if deep restorations are not placed over a protective film. Some have advocated the use of glass-ionomer cement as a lining under resin composite restorations in dentin. The concept of glass-ionomer cements (GICs) was introduced to the dental profession in the early 1970's. Current GICs may contain poly(acrylic acid) or a copolymer. Higher-molecular-weight copolymers may also be used to improve the physical properties of some GICs. Stronger and less-brittle hybrid materials have been produced by the addition of water-soluble compatible polymers to form light curing GIC formulations. The ion-leachable aluminosilicate glass powder, in an aqueous solution of a polymer or copolymer of acrylic acid, is attacked by the hydrated protons of the acid, causing the release of aluminum and calcium ions. Salt bridges are formed, and a gel matrix surrounds the unreacted glass particles. The matrix is adhesive to mineralized tissues. Provisions must be made for maintenance of the water balance of restorations for the first 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292463 TI - Biodegradation of dental composites/glass-ionomer cements. AB - Studies of the degradation processes, types of tests, and measurements and analyses of substances leaching out from resin-based composite materials and glass-ionomer cements are reviewed. For both types of materials, the initial release rate rapidly decreases to a low, but nearly constant, level. For composites, various types of degradation processes have been demonstrated. Elements from filler particles and degradation products from the resin (e.g., formaldehyde) leak out. Many substances are not properly identified. It is, however, difficult for in vitro and in vivo degradation to be compared. For glass ionomers, a total disintegration of a surface layer is observed, together with a slow release of elements from the bulk. Of the elements released, fluoride is the most interesting. Marked differences have been shown between in vitro and in vivo solubility tests. PMID- 1292464 TI - Local and systemic responses to dental composites and glass ionomers. AB - For many years, the dental profession worked mainly with rather inert restorative materials that had a limited contact with vital tissue, and the opportunity for local and systemic complications was minimal. However, conditions have changed in recent years where the two leading non-mercury-containing materials, resin composites and glass-ionomer cements, are chemically active compounds and can have detrimental effects on pulp tissue. With the advent of light-curing techniques with incremental layering, resin component formulae that were formerly found to be quite irritating to the pulp have become less so with the elimination of the need for matrices and pressure for good adaptation to be gained. As experience revealed the deficiencies and dangers of ultraviolet-light-curing techniques, visible-light-curing systems were developed that provided greater depth of cure, a higher degree of polymerization with less shrinkage with incremental layers, and less porosity. When glass-ionomer cements (GICs) were first introduced, with just one acid (polyacrylic), pulpal responses were classified as bland. With the addition of many more acids to enhance certain characteristics and reduce the setting time, GICs have become more irritating, especially when used as luting agents in areas where the remaining dentin thickness is 0.5 mm or less. Gold foil and amalgam are inert and innocuous restorative materials but require pressure for condensation which creates an exaggerated inflammatory response. This presentation emphasizes the pulpal responses and side-effects of these non-mercury-containing restorative materials and how to keep them within an acceptable range of biocompatibility. Despite the lack of any substantial appearance of soft tissue and systemic responses to resin composites and GICs, the results of a survey of recent literature are included. PMID- 1292465 TI - Dental composites/glass ionomers: clinical reports. AB - Composites and glass ionomers have not been extensively tested in clinical trials for biological safety. Most clinical evaluations have looked at other factors, such as retention, wear, or color. The primary evaluation criterion used in clinical trials is post-operative sensitivity. Sensitivity does not seem to have any correlation to pulpal inflammation. Inflammation can be the result of mechanical, thermal, chemical, and bacterial insults. It is complicated for individual contributions to be separated in short-term studies. General usage of these materials over about 20 years indicates a high benefit-to-risk ratio. Despite some complaints of sensitivity with some glass-ionomer compositions, both composites and glass ionomers are relatively trouble-free. There is no evidence of short-term or long-term risk. Toxicological studies have focused almost exclusively on pulpal reactions. Systemic reactions have not been closely examined, although there is no suspicion of any problems after virtually billions of procedures in the United States. New glass-ionomer cements are similar to contemporary composite formulations. Continued development of these materials may ultimately produce an amalgam replacement material that is economically and philosophically desirable to general dentists. PMID- 1292466 TI - Problems and benefits associated with restorative materials: side-effects and long-term cost. AB - The paper reviews data on biological side-effects of dental materials on patients and also on personnel who routinely handle the materials. The incidence of adverse effects is low--in one study indicated to be 1:700 for all types of treatments. For individual types of materials, it will be significantly lower, and for restorative materials, probably in the 1:10,000 to 1:20,000 range. Allergic reactions are the most common type of adverse effect of dental materials. Lichenoid reactions on the oral mucous membrane adjacent to amalgam restorations are the most frequently encountered side-effects for a specific group of restorative materials. Cost analyses were based on reports of longevity of different restorations and the cost of restorations at the time of placement. Amalgam restorative therapy was more cost-effective than composite restorations and gold castings. PMID- 1292467 TI - Dental ceramics: the state of the science. AB - This review covers the properties of dental ceramics. Castable systems, bioactive glass, PMF systems, CAD/CAM, and ceramic brackets in orthodontics are briefly discussed. Many of the advances made between 1960 and 1975 were directed toward the understanding, controlling, and developing of new ceramic processes. New and deeper understanding of the structure of non-crystalline solids, structural imperfections, sintering physics, and other physical phenomena related to the melting and solidification processes has brought ceramics from the near-total art form process of the mid-century to the status of a highly sophisticated science it enjoyed in the 1980's. PMID- 1292468 TI - Degradability of dental ceramics. AB - The degradation of dental ceramics generally occurs because of mechanical forces or chemical attack. The possible physiological side-effects of ceramics are their tendency to abrade opposing dental structures, the emission of radiation from radioactive components, the roughening of their surfaces by chemical attack with a corresponding increase in plaque retention, and the release of potentially unsafe concentrations of elements as a result of abrasion and dissolution. The chemical durability of dental ceramics is excellent. With the exception of the excessive exposure to acidulated fluoride, ammonium bifluoride, or hydrofluoric acid, there is little risk of surface degradation of virtually all current dental ceramics. Extensive exposure to acidulated fluoride is a possible problem for individuals with head and/or neck cancer who have received large doses of radiation. Such fluoride treatment is necessary to minimize tooth demineralization when saliva flow rates have been reduced because of radiation exposure to salivary glands. Porcelain surface stains are also lost occasionally when abraded by prophylaxis pastes and/or acidulated fluoride. In each case, the solutes are usually not ingested. Further research that uses standardized testing procedures is needed on the chemical durability of dental ceramics. Accelerated durability tests are desirable to minimize the time required for such measurements. The influence of chemical durability on surface roughness and the subsequent effect of roughness on wear of the ceramic restorations as well as of opposing structures should also be explored on a standardized basis. PMID- 1292469 TI - Dental amalgam: the materials. AB - The goal of this presentation is to describe the material as it is used clinically, explain why small quantities of Hg can be released, and suggest ideas for amalgams that do not release mercury. A set amalgam is a dynamic material that undergoes many microstructural changes during clinical use, related to both the elevated temperature and corrosion-prone environment in the mouth and mechanical forces applied to the restoration. Amalgams can be divided roughly into two groups by their copper content: low Cu (traditional) and high Cu. High Cu amalgams generally perform better clinically, but all amalgams corrode to some extent in the mouth. Some corrosion is deemed to be a positive factor, because corrosion product deposition reduces leakage at the margins of restorations; that is, the restorations are partly self-sealing. One of the reasons cited for the improved clinical performance of high-Cu amalgams over low-Cu amalgams is that the corrosion-prone phase, gamma 2, is nearly eliminated in high-Cu amalgams. Future research should involve improvements in the clinical performance of dental amalgams, studies of the mercury release from various types of amalgams and the toxic potential of this exposure, and the development of new amalgam systems that reduce the mercury exposure. Although the longevity of modern amalgams is impressive, it is important for their stability to be increased both clinically and microstructurally. An amalgam should be developed with a stable microstructure that, once set, would not change during clinical use. Microstructural changes lead to clinical deterioration. A stable system would not corrode, and the matrix transformation gamma 1 to beta 1 would be prohibited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292470 TI - New perspectives in the differentiation of bone-forming cells. AB - Bone formation comprises a complex but ordered sequence of events which involves the proliferation and differentiation of chondrogenic and osteoblastic precursor cells ultimately leading to the formation of a calcified extracellular matrix. This process can be observed in vivo but under these conditions is difficult to study at the molecular level. A number of in vitro models have been developed which recapitulate discrete elements of this process. Using these models, detailed information has been obtained regarding the differentiation of bone forming cells and the molecular biology of the mineralization process. It has been shown that, in vitro, osteoblastic precursor cells can form a mineralized matrix similar to that seen in vivo. This calcification process was shown to consist of three interdependent phases: proliferation, matrix maturation and mineralization. Each of these phases was characterized by the expression of particular genes. Osteoblast precursors have been cloned and consequently shown to be able to differentiate in vitro into a number of other mesenchymal cells, supporting the theory that osteoblasts are derived from multipotent mesenchymal cells. It is possible that markers derived from these models could be used in the future to extend our knowledge of bone formation in vivo. PMID- 1292471 TI - Interleukin-11 and its receptor. AB - Interleukin (IL)-11 is a bone marrow fibroblast derived cytokine with a wide spectrum of activities in different biological systems. It has been shown that IL 11 supports the growth of certain types of plasmacytoma and hybridoma cells, enhances antigen-specific antibody responses, synergizes with IL-3 in supporting megakaryocyte colony formation, acts synergistically with IL-3 in shortening the G0 period of early progenitors, induces the synthesis of acute phase proteins, and inhibits lipoprotein lipase activity and adipocyte differentiation. The human IL-11 gene, which is localized at 19q13.3-13.4, consists of five exons and four introns. Initial biochemical characterization has identified a 151 kDa protein as the potential IL-11 binding subunit of the receptor complex. Because of the overlapping biological activities between IL-6 and IL-11, we compared the signal transduction pathways mediated by IL-6 or IL-11 in cell lines responsive to both cytokines. Results from protein tyrosine phosphorylation and immediate response gene expression suggest that there are convergent and divergent points along the signal transduction pathways utilized by IL-6 or IL-11. The IL-6 signal transducer, gp130, appears to be involved in the IL-11 mediated signaling. Other cytokines such as leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor have also been shown to utilize gp130 as a signal transducer. The significance of growth factor sharing common biological activities and signaling pathways will be discussed. PMID- 1292472 TI - Iron metabolism in Pseudomonas: salicylic acid, a siderophore of Pseudomonas fluorescens CHAO. AB - Under iron-starvation conditions of growth, Pseudomonas fluorescens CHA0, a soil isolate involved in phytopathogenic fungi antagonisms, produced, together with pyoverdine, a second iron-chelating compound which was purified and identified by spectroscopy, HPLC and 1H-NMR to be salicylic acid. Mutants unable to synthesize pyoverdine overproduced this compound by a factor of 9-14. The biosynthesis of salicylic acid was under iron control; it was fully inhibited by 5 microM added iron in the growth medium. In contrast, salicylic acid of either bacterial or commercial origin facilitated labeled iron incorporation in iron-starved cells. Based on these two relationships observed with bacterial iron metabolism it is concluded that salicylic acid has a siderophore function for this strain. PMID- 1292473 TI - The effect of selenium on the function of the anion transporter (Band 3) of erythrocyte membranes. AB - The transport activity of Band 3 of spectrin-stripped inside-out erythrocyte membrane vesicles (IOVs) or resealed ghosts was enhanced in the presence of trace amounts of Na2SeO3 (0.2-0.5 p.p.m.); however, at higher concentrations of Na2SeO3 (> 4.0 p.p.m.), an inverse result was obtained. Reassociation of spectrin with IOVs has no effect either on the transport activity of Band 3 or on the enhancement of its activity by Na2SeO3. Sulfhydryl reagents (p chloromercuribenzoic acid and N-ethylmaleimide) could also inhibit Band 3 activity and eliminate the selenium effect. It is suggested that SH groups are involved in anion transport of Band 3 and that the selenium effect is based on the interaction of SH groups of Band 3 with Na2SeO3. PMID- 1292474 TI - Lipopolysaccharide-binding factors are present in bovine serum. AB - Response of vertebrates to bacterial lipopolysaccharide (LPS) may be regulated, in part, by serum factors that influence the bioavailability and cellular binding affinity of LPS. Using 3H- or 14C-labeled LPS, or a novel fluorescence-based assay for detection in CsCl isopycnic density gradients, our studies indicate the existence of factors in adult and fetal bovine serum that bind LPS. Within serum containing gradients, labeled LPS appeared in two peaks: least-dense fractions (< or = 1.30 g/cm3) and at 1.35 g/cm3. This profile was different from that of gradients without serum, where LPS appeared at 1.38 g/cm3. Binding of LPS to serum component(s) at 1.35 g/cm3 was rapid (< 1 min), saturable and specific. A partial shift (50%) of LPS from a density of 1.35 g/cm3 to other serum components at < or = 1.30 g/cm3 occurred over 1 h. Flow cytometric analysis indicated that bovine serum factors influence the binding of LPS to blood monocytes, because monocyte-FITC-LPS association increased in the presence of bovine serum. PMID- 1292475 TI - Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in established and malignant fibroblasts. AB - Studies on glutathione (GSH) metabolism in an established baby hamster kidney fibroblast cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY) have revealed a significant stimulation of intracellular GSH peroxidase (GSHpx) activity (selenium-independent plus selenium-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (i.e. GSH reductase and GSH S-transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting that some protection was afforded by the alpha-tocopherol. PMID- 1292476 TI - Effect of saffron on thymocyte proliferation, intracellular glutathione levels and its antitumor activity. AB - Liposome encapsulation of saffron effectively enhanced its antitumor activity towards Sarcoma-180 (S-180) and Ehrlich ascites carcinoma solid tumors in mice. Significant inhibition (P < 0.001) in the growth of these tumors was observed as compared with vehicle (control) mice. In the presence of phytohemagglutinin (PHA), a T cell mitogen, saffron stimulated non-specific proliferation of lymphocytes in vitro. The intracellular reduced glutathione and related enzymes, i.e. glutathione reductase and glutathione-S-transferase, of S-180 tumor cells were significantly elevated when incubated with saffron, possibly acting to maintain functional levels of other antioxidants. Our studies indicate the antioxidant activity of saffron. PMID- 1292477 TI - The ability of bacteria to synthesize a new cyclopyrophosphate correlates with their tolerance to redox-cycling drugs: on a crossroad of chemotherapy, environmental toxicology and immunobiochemical problems. AB - Many redox-cyclers were recently shown to induce, in some bacterial species, large-scale biosynthesis of a new 2-methylbutan-1,2,3,4-tetraol-2,4 cyclopyrophosphate believed to be involved in anti-stress reactions. In the present study Mycobacterium smegmatis, Micrococcus luteus and Brevibacterium ammoniagenes were shown to begin synthesis of the new cyclopyrophosphate when cultivated in a medium containing furacilin or furadonin (widely used nitrofuran antibacterial drugs) and to maintain close to normal growth rates, whereas Staphylococcus aureus, Bacillus subtilis and Escherichia coli were inhibited by the drugs and were unable to synthesize the cyclopyrophosphate compound. Preferential binding of Mg2+ and Cd2+ with one or other phosphoryl groups of the cyclopyrophosphate, which was indicated by selective changes of 31P-NMR chemical shifts and intramolecular hydrogen bonding, is suggested as a reason for this selectivity. PMID- 1292478 TI - [Reduced influence of penile disability on the mating capacity of male staggerer mice]. AB - Most staggerer mutant mice do not mate spontaneously. This deficiency may be attributed to a penile disability (during erection, the penis in extension is directed backward). The main characteristics of this phenomenon and its involvement in the reproduction of the staggerer mutant have been considered in our study. Seventy-four percent (n = 66) of staggerer males presented this temporary abnormality at least once. It appeared when the males were 84 +/- 37-d old (M +/- SD). In most animals the penile abnormality was labile and did not exceed 1 wk duration in 48% (n = 32) of the males. Three males mated in spite of presenting this abnormal erection. Moreover, 25% of males (n = 23) did not present this disability; nevertheless, most of them (91%) still did not reproduce. Other mechanisms are certainly responsible for the inefficient mating. In any case, the influence of penile disability on this deficiency appears to be weak. PMID- 1292479 TI - Ultrastructural study of nucleolar changes in rat embryos during diapause and reactivation. AB - Changes in nucleolar ultrastructure were studied in preimplantation rat embryos before diapause (d 5), during diapause (d 6, 7 and 8) and after reactivation brought about either by in vitro culture for 24 h (d 7 and 8) or by estradiol-17 beta treatment of the mothers (d 11). Before diapause, fully developed nucleoli contained several low-density fibrillar centers surrounded by a dense fibrillar component and an abundant granular component. This type of nucleolus indicates a high activity of ribosomal RNA synthesis. During diapause, nucleoli revealed a disorganization of the fibrillar and granular elements typical of a diminution in transcriptional activity. During reactivation, nucleoli progressively returned to a reticulo-fibrillar configuration characteristic of the onset of intense transcriptional activity. It is concluded that the structure of the nucleolus in rat preimplantation embryos corresponds to the level of transcriptional activity and is a reliable model for studying structure-function relationships during early development. PMID- 1292480 TI - The effect of breed-type and castration on bone growth and distribution in cattle. AB - Data from carcasses of 210 cattle (119 bulls and 91 steers) from 4 breed types, serially slaughtered from approximately 200-800 kg kg liveweight were used to test the hypothesis of similar gender dimorphism among breeds in relation to carcass bone growth and distribution. Relative to total bone weight, breed types tended to have similar growth rates for all bones other than the cervical vertebrae, ribs, tibia and fibula, and tarsus. Adjusted to the same total bone weight there were significant differences among breed types in bone weight distribution, but the differences were very small and probably of little economic importance. Castration stimulated growth of the lumbar vertebrae, hindlimb bones, patella and hindquarter bones but inhibited growth of the ribs, scapula, carpus, forelimb bone, and forequarter bone. At the same total bone weight, steers as compared to bulls showed a shift in bone weight distribution towards the hindquarter, pistol and long bones. There were small but significant breed x gender interactions in the distribution of some bones. PMID- 1292481 TI - The possible involvement of protein kinase C(s) and inositol phosphate metabolism in the basal but not in the prolactin stimulated casein release by the lactating rabbit mammary epithelial cell. AB - The secretagogue effect of prolactin (PRL) on casein release by epithelial mammary cells has been previously related to stimulation of the phospholipase A2 arachidonic acid cascade. In order to determine whether other intracellular pathways are implicated in this secretagogue effect, different agents acting on protein kinase C (PKC) and phospholipase C (PLC) activity have been assessed in vitro in lactating rabbit mammary gland fragments. Phorbol ester (20 nm TPA and 1 oleoyl-2-acetyl-sn-glycerol (10 microM (OAG) stimulated newly synthesized casein secretion and potentiated the PRL secretatogue effect. However, 100 microM quercetin, 100 microM H-7 and 5 and 20 nM staurosporine did not inhibit the latter effect. Exogenous PLC did not stimulate casein secretion. PRL did not affect production of inositol phosphates (IPs) during 10 or 60 min exposure. These results show that PKC activation may increase basal levels of casein secretion, and demonstrate that PRL does not act primarily via PKC activation or by PLC activation to stimulate casein secretion. PMID- 1292482 TI - Intestinal transfer of manganese: resemblance to and competition with calcium. AB - The effect of calcium, phosphate and the sugars lactose and sorbitol on the intestinal absorption of manganese were studied in adult male rats. Gastric gavage showed that lactose (100 mM or 200 mM) increased the hepatic retention of 54Mn, while phosphate decreased it. In situ ileal loop studies indicated that Mn absorption was normally complete in 30 min. Sorbitol had no effect on uptake during this period, but extended Mn absorption from 30 min to 120 min. Low concentrations of Mn (10 microM) did not alter the enhancing effect of lactose on calcium transport (10 mM), but the enhancing effect of lactose on Mn transport was blocked by this high calcium concentration. Intestinal alkaline phosphatase activity was rapidly stimulated by Mn. These similarities plus the competition between cations, especially calcium, suggest that a common mechanism exists in their intestinal transport. PMID- 1292484 TI - Ingestion, Digestion, Absorption, Metabolism Seminar. 28th meeting of the Association Francaise de Nutrition. Dijon, France, 8-9 October 1991. Abstracts. PMID- 1292483 TI - Effects of protein kinase inhibitors on pig oocyte maturation in vitro. AB - Normal oocyte maturation depends on signal transmission between granulosa cells and the oocyte. We have analysed the effects of inhibiting (I) cyclic AMP dependent protein kinase (protein kinase A, PK-A), (II) Ca2+/phospholipid dependent protein kinase (protein kinase C, PK-C) and (III) calmodulin (CaM) on pig oocyte maturation in vitro, protein synthesis and phosphorylation. The inhibition of PK-A using a specific inhibitor H8, decreased the maturation rate (rate of germinal vesicle breakdown, GVBD) of cumulus-enclosed pig oocytes in a dose-dependent manner by approximately 12%, reaching a plateau at 100 microM. The inhibition of PK-C with H7, an inhibitor with some side-effects on PK-A, decreased the maturation rate of cumulus-enclosed oocytes in a dose-dependent manner to a maximum of 20% at a concentration of 100 microM. The calmodulin antagonist W7 up to a concentration of 200 microM had no effects on maturation of cumulus-enclosed pig oocytes. None of the inhibitors (H7, H8 and W7) altered the patterns of protein synthesis of either pig oocytes and cumulus cells after maturation in vitro. Oocyte phosphoprotein patterns were, however, clearly changed by W7. Cumulus cell protein phosphorylation patterns were changed by all 3 agents. Since inhibition of cyclic AMP and Ca2+ phospholipid pathways by PK-A and PK-C blocking chemicals affected only a limited proportion of oocytes (12 and 20%, respectively) and inhibition of Ca2+ binding to CaM was without effect on oocyte maturation, we conclude that these pathways modulate rather than regulate oocyte maturation in the pig. PMID- 1292485 TI - [Investigation on the plant origin and commodity of Chinese drug bixie]. AB - An investigation has been made on the Chinese drug Bixie available in drug market, its folk uses and plant origin in different districts in China. The results reveal that the drug Bixie presently used in different regions in China are derived from 24 species belonging to genus Dioscorea (Family Dioscoreaceae); genus Smilax and Heterosmilax (Family Liliaceae). PMID- 1292486 TI - [Research on the resources of medicinal materials in Yili]. PMID- 1292487 TI - [Morphology and histology of Usnea Longissima Ach]. PMID- 1292488 TI - [A study on suitable storage conditions for Melaphis chinensis (Bell) Baker]. AB - It is a key procedure for breeding Chinese gallnuts to put the collected Melaphis chinensis on winter host Mnium cuspidatum. The result shows that the most suitable storage condition for the collected Me. chinensis is to store it for four days in shade before putting to winter host. PMID- 1292489 TI - [Studies on film-covered soil setting seedling of Panax notoginseng (Burk.) F.H. Chengfu]. AB - Film-covered soil setting seedling can markedly raise the yield of seedling and seedling establishment of Panax notoginseng, thus providing higher economic benefit. The increase of yield in trial plots was about 8.82%-24% higher than the control. PMID- 1292490 TI - [Pharmacological studies on erzhi pills]. AB - The experimental results show that Erzhi Pills can markedly increase the weights of immunological organs in mice and antagonize the immunosuppressive action of prednisolone. The diameter of SRID precipitating ring, the hemolytic ability of PFC and the clearance rate of i.v. charcoal particles in mice can all be increased by the pills. Erzhi Pills also protect mice from CCl4 intoxication. Steamed Ligustrum lucidum has the same action as Erzhi Pills. PMID- 1292491 TI - [Comparison of constituents in Pueraria thomsonii Benth before and after processing]. AB - Determinations of aqueous extract, alcoholic extract, flavonoids and puerarin as well as ten inorganic elements in Pueraria thomsonii have been made before and after processing. The results showed that the above mentioned ingredients all varied in amount. PMID- 1292492 TI - [Analysis of active ingredients in wuren liguid]. AB - The active ingredients and their relative concentration in Wuren liquid were analyzed by GC/MS. It has been found that there are concentrative antimicrobiological ingredients in the liquid such as phenols, benzoic acids, fatty acids, and so on. The results have confirmed the effectiveness of Wuren liquid in disinfection, germ-killing and treatment of skin diseases. PMID- 1292493 TI - [Studies and preparations of fufang danshen granules]. AB - With the preparation of borneol-beta-cyclodextrin inclusion compound, the stability of the product was improved. In the studies on quality standards, TLC method was used in the identification of three medicinal ingredients and TLC ultraviolet spectrophotometry was used in the content determination of the chemical constituent tanshinone II A in Salvia miltiorrhiza. PMID- 1292494 TI - [Chemical constituents of the root of Oplopanax elatus Nakai]. PMID- 1292495 TI - [Chemical constituents of Cirsium segetum (Bge.) Kitam]. PMID- 1292496 TI - [Diterpenoid alkaloids of Aconitum sinomontanum var. angustius W.T. Wang]. AB - Three diterpenoid alkaloids were isolated from Aconitum sinomontanum var. angustius distributed in south Gansu. They were identified as ranaconitine (I), lappaconitine (II), 3-acetylaconitine (III) on the basis of spectral evidences (UV, IR, HNMR, 13CNMR, MS). PMID- 1292498 TI - [Determination of naphthoquinone in zicao]. AB - A TLC-spectrophotometric method for the separation and determination of the naphthoquinones in Zicao is described. The sample solution was applied at a point 1 cm from the bottom edge of a silica gel G plate. A mixture of n-hexane-acetone chloroform-glacial acetic acid was used as the developing solvent. The plate was saturated for 30 min and developed. The spots were scraped and extracted with chloroform for spectrophotometric determination at 523nm. The method has been applied to the analysis of different samples. PMID- 1292497 TI - [Chemical constituents from the root bark of Dictamnus dasycarpus Turcz]. AB - Rutaevin was isolated from the root bark of Dictamnus dasycarpus. It has been obtained from genus Dictamnus for the first time. PMID- 1292499 TI - [Protective effects of Panax quinquefolium saponin on oxidative damage of cultured rat cardiac cells]. AB - When cultured cardiac cells of rats were exposed to X-XOD containing medium, the absolute values of electronic parameters were decreased the percentage of beating clusters reduced and the microscopic structure destroyed. PQS significantly converted all the indices, which shows that PQS can protect the cells from oxidative damage. PMID- 1292500 TI - [Inotropic action of Astragalus membranaceus Bge. saponins and its possible mechanism]. AB - Astragalus membranaceus saponins (AMS) 50-200 micrograms/ml had a positive inotropic action on the isolated working heart of rats, but in the case of 30 micrograms/ml the inotropic action turned negative. The contractility recovered after washing out the AMS. Strophanthin K performed in a similar manner as AMS. AMS 500 micrograms/ml decreased the resting potential of cultured rat heart cells by 10 mV. The results suggest that AMS plays its inotropic role through influencing the Na-K-ATPase. PMID- 1292501 TI - [Antitumor effect of castor oil extract]. PMID- 1292502 TI - [Adolf Butenandt lecture 1992. Molecular mechanisms of mouse embryogenesis]. PMID- 1292503 TI - A new ultrasensitive bioluminogenic enzyme substrate for beta-galactosidase. AB - A derivative of D-luciferin, D-luciferin-O-beta-galactoside, was synthesized and used as highly sensitive substrate for beta-galactosidase. The substrate was physicochemically characterized. Enzymatic cleavage of the new compound by beta galactosidase was demonstrated and kinetic constants Km, Vmax, kcat and kcat/Km have been determined. The compound has been proved to be a highly sensitive substrate for beta-galactosidase, permitting a limit of detection of 3.7 x 10( 19) mol of enzyme per assay. PMID- 1292504 TI - Partially phosphorylated glycogen phosphorylase in the lugworm Arenicola marina, its regulatory function during hypoxia. AB - Glycogen phosphorylase (GPase) from the body wall of the lugworm Arenicola marina (Annelida, Polychaeta) probably exists as a phospho-dephospho hybrid (GPase ab). The hybrid was identified by phosphorylation of purified lugworm GPase b (unphosphorylated form) with rabbit muscle GPase kinase and [gamma-32P]ATP. The completeness of phosphorylation was checked on DEAE-Sephacel. Only one GPase form was eluted. Its 32P incorporation was determined to 0.52 +/- 0.08 mol 32P/100,000 x g protein (n = 4). This GPase ab produced by in vitro phosphorylation has shown similar dependences on AMP and caffeine as GPase extracted from the body wall of the lugworm. Its reversible conversion with endogenous phosphatase and kinase to GPase b has also been demonstrated while a completely phosphorylated form (GPase a) was not detected neither in vivo nor in vitro. Lugworm GPase ab has shown a 2.4-fold higher specific activity as GPase b. The Km for P(i) was 16 mmol/l in absence and 13 mmol/l in presence of AMP. Half maximum activation by AMP was reached at 9 mumol/l. IMP up to 10 mmol/l did not activate and ATP up to 4 mmol/l did not inhibit GPase ab in absence of AMP. PMID- 1292505 TI - Brain-restricted amyloidoma of immunoglobulin lambda-light chain origin clinically resembling multiple sclerosis. AB - Cerebral amyloid deposits restricted to the white matter and associated with intracerebral lymphoma were biochemically identified. The patient died at 58 years of age after 37 years of illness with progressive neurological symptoms clinically indicative of multiple sclerosis. Pathomorphologically, spongiform alteration and demyelinization of the white matter in the vicinity of the amyloid deposits was detected and systemic amyloidosis excluded. Immunohistochemically, the amyloid was found to be of immunoglobulin lambda-light chain origin. To establish the nature of this amyloid, its fibrils were extracted and the amyloid fibril proteins isolated by size exclusion chromatography. Immunochemically, the purified amyloid fibril proteins were shown to be of immunoglobulin lambda-light chain origin. This finding was substantiated chemically. Since the N-terminal amino acid was blocked, tryptic peptides were isolated by reversed phase HPLC. The amino-acid sequence of two major peptides revealed homology with the variable region of the immunoglobulin lambda-light chain. This report defines a novel local A lambda-amyloid disease restricted to the white matter of the brain. PMID- 1292506 TI - Modulation of macrophage response to interleukin-2 immunotherapy by interleukin-3 in cancer patients. AB - It has been observed that neopterin, a specific marker of macrophage activation, increases during cancer immunotherapy with IL-2, and this effect is mediated by interferons produced by IL-2-stimulated lymphocytes. Moreover, our previous studies have shown that neopterin rise during IL-2 immunotherapy is associated with an enhanced release of soluble IL-2 receptor (SIL-2R), which may suppress IL 2-dependent immune functions. This finding would suggest that neopterin increase may be related to the generation of suppressive events, which occur during IL-2 immunotherapy. On the basis of the documented modulatory effect of IL-3 on macrophage functions, we have evaluated the influence of IL-3 on neopterin secretion during IL-2 immunotherapy. The study was performed in advanced lung cancer patients. We have investigated 9 immunotherapeutic courses consisting of IL-2 (6M IU/day s.c. for 5 days/week for 3 weeks) plus IL-3 (1 microgram/(kg x day) i.v. for 14 days, starting 7 days before IL-2). The results were compared to those found during 18 courses with IL-2 alone. Mean neopterin levels increased significantly during IL-2 alone, but not in response to IL-3 plus IL-2. SIL-2R rise was significantly higher during IL-2 than during IL-3 plus IL-2. Mean numbers of NK cells and activated lymphocytes increased significantly in both groups of patients, but were significantly lower at the end of the treatment in patients receiving IL-2 alone than in those treated with IL-3 plus IL-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292507 TI - Cloning and sequence analyses of cDNAs encoding aminoacylase I from porcine kidney. AB - cDNAs encoding L-aminoacylase (EC 3.5.1.14) were isolated from a lambda gt10 cDNA library derived from porcine kidney mRNA. The clones were identified by hybridization with a synthetic oligonucleotide probe based on partial peptide sequences, or with a DNA probe encoding human aminoacylase I. Several cDNA clones isolated from the library had a length of about 1.3 kbp. They contained an open reading frame of 1218 bp encoding a polypeptide of 406 amino acids. The deduced amino-acid sequence contains the known peptide sequences; in addition, M(r) (45.3 kDa) and amino-acid composition of the predicted polypeptide match those of purified aminoacylase I. Data base searches did not reveal significant sequence homologies of aminoacylase I with other well-known amidases. PMID- 1292508 TI - Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene. AB - The cDNA and complete gene encoding mouse acid sphingomyelinase (ASM) has been isolated using a homology screening approach. Comparison with the human sequence shows 81% sequence identity at cDNA level and 82% at the protein level. Homology is markedly reduced in the N-terminal region, especially in the presumed signal peptide. The six-exon gene structure is similar to the human one, except for the position of Alu1 elements. The alternatively used splice site 40 bp downstream of the human exon 2 is not conserved in the mouse gene and accordingly no such alternative splicing was found in mouse. PMID- 1292509 TI - The properties of monoclonal antibody against sepiapterin reductase from fat body of the silkworm, Bombyx mori. AB - A specific monoclonal antibody prepared for the 29-kDa a subunit of silkworm fat body sepiapterin reductase (SPR) was able to recognize the subunit in crude extract of fat body after SDS treatment. Although SPR from the silkworm fat body has biochemical properties similar to those reported for SPR from mammalian sources, especially rat erythrocytes, the antibody failed to recognize the 28-kDa subunit of rat erythrocyte SPR. This result indicates that SPR from silkworm fat body has a different amino-acid sequence from that of the rat erythrocyte enzyme. Sepiapterin reductase activity has not been found in crude extract of fat body from the silkworm mutant lemon. Although the antibody recognized only 29-kDa protein in the crude extract of silkworm fat body from normal strain after SDS treatment, the antibody recognized only an approximately 80-kDa protein in the crude extract of the lemon mutant after SDS-treatment. PMID- 1292510 TI - Synthesis of N-acetyl-9-O-acetylneuraminic acid alpha-p-amino-phenylthioketoside and its application as ligand in the affinity chromatography of a lectin with preferential affinity to O-acetylated sialic acids. AB - The N-acetyl-9-O-acetylneuraminic acid-alpha-p-aminophenylthioketoside 7 was synthesized as a sialidase-stable ligand for the affinity chromatography of a lectin with preferential affinity to O-acetylated sialic acids. The thioketoside was prepared by phase-transfer-catalysed glycosidation followed by Zemplen deacetylation. Regioselective acetylation of the completely de-O-acetylated derivative was practised by two different methods. The acetylation with trimethylorthoacetate did not show the desired selectivity for hydroxyl groups; in addition to the acetylation in position 9 extensive formation of an acetimidate ester derivative with the amino-group in the aminophenyl-moiety was observed. However the esterification with N,N-dimethylacetamide dimethyl acetal resulted in an exclusive acetylation of the hydroxyl-group in position 9. After catalytic hydrogenation this ligand was immobilized both directly and by a six carbon long spacer group to the agarose matrix. The adsorbents were applied in the affinity chromatography of the lectin and their binding capacity and selectivity compared to those of the formerly used mucin matrix. In both respects the thioketoside coupled by the spacer turned out to be a better ligand for the isolation of the lectin than the mucin. PMID- 1292511 TI - Pteridines in the yellow-colored chromatophores of the isopod, Armadillidium vulgare. AB - Biochemical analyses of the dorsal integument of the isopod, Armadillidium vulgare, revealed that sepiapterin, biopterin, pterin, isoxanthopterin and uric acid accumulated in the yellow-colored chromatophores which are distinguishable from ommochrome chromatophores. The pattern of the yellow-colored chromatophores in the female is externally observable at the dorsal surface of the integument as yellow markings. In contrast, the yellow-colored chromatophores are not externally observable in the male, since they are covered by an ommochrome chromatophore layer. The content of both sepiapterin and biopterin in the male chromatophores was about two times greater than that in the female. The yellow colored chromatophores were observable by light microscopy as pigmented granules. Electron microscopy showed that morphological properties of the granules were similar to those of pteridine granules which contain uric acid occurring in the silkworm integument. These facts indicate that both pteridines and uric acid in the integument of A. vulgare are localized in the pigmented granules of the yellow-colored chromatophores. PMID- 1292513 TI - 2-hydroxy-4,4-dimethyl-2-(4-tolyl)-morpholinium bromide. AB - C13H20NO2+.Br-, M(r) = 302.2, monoclinic, P2(1)/c, a = 8.697 (2), b = 12.741 (3), c = 12.940 (2) A, beta = 103.39 (2) degrees, V = 1394.9 (8) A3, Z = 4, Dx = 1.439 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 29.1 cm-1, F(000) = 624, T = 296 K, R = 0.038 for 1662 observations with I > 2 sigma (I) (of 2460 unique data). The morpholinium ring adopts the chair conformation with endocyclic torsion angle magnitudes 49.1 (4)-61.9 (4) degrees. The hydroxyl group is in the axial position of the morpholinium ring, with C--OH bond distance 1.401 (4) A. The hydroxy H atom points towards a Br ion; the interaction has O...Br distance 3.292 (2) A, H...Br distance 2.61 (3) A, and angle at H 160 (4) degrees. PMID- 1292512 TI - Intra- and interchain disulfide bridges of the human J chain in secretory immunoglobulin A. AB - All intra J chain disulfide bridges of human sIgA, the disulfide bonds between the J chain and the two IgA monomers, and one inter IgA monomer disulfide bridge were determined. sIgA was isolated from colostrum of healthy women and digested with IgA1-specific protease followed by cyanogen bromide cleavage. This procedure generated fragments of 140 kDa, 60 kDa, and 28 kDa. The 28-kDa polypeptide comprised the complete J chain covalently bound to two alpha 1 chain octapeptides derived from the C-termini of two alpha 1 chains. The 28-kDa fragment was digested with trypsin. The resulting peptides were purified by RP-HPLC, and subsequently characterized by amino-acid analysis, mass spectrometry, and gas phase sequencing. These data unequivocally show that the J chain cysteines C1-C6, C4-C5, and C7-C8 form intra chain disulfide bridges. The second (C2) and the third (C3) J chain cysteines are disulfide linked to two alpha chain cysteines (C17) joining the two IgA monomers of sIgA tail to tail. The remaining two alpha chains of the two monomers are directly bound to each other via their ultimate cysteines (C17-C17). A new model for the J chain in sIgA is presented. PMID- 1292515 TI - Development notes & DNA. PMID- 1292514 TI - Structure of 5 beta-pregnane-3 alpha, 6 alpha, 17 alpha-triol triacetate. AB - C27H40O7, M(r) = 476.61, monoclinic, P2(1), a = 17.440 (5), b = 13.267 (1), c = 12.168 (2) A, beta = 110.49 (8) degrees, V = 2637.3 (9) A3, Z = 4, Dx = 1.20 g cm 3, lambda (Cu K alpha) = 1.5418 A, mu = 7.04 cm-1, F(000) = 1032, T = 293 K, R = 0.048, wR = 0.068 for 5590 observed reflections with (Fo)2 > 2 sigma [(Fo)2]. The structure contains two crystallographically independent molecules in the asymmetric unit that have almost identical geometry. Rings A, B and C have chair conformations and the D ring assumes a half-chair conformation in both molecules. The progesterone side chain has a conformation typical for other 17 alpha-ester steroids; the C(16)--C(17)--C(20--O(20) torsion angles are -18.2 (5) and -15.0 (4) degrees for the first and the second molecule respectively. PMID- 1292516 TI - Clinical evaluation of a prototype glucose electrode. AB - A new prototype direct reading glucose electrode working with glucose oxidase and hydrogen peroxide was preliminarily tested clinically during insulin-induced hypoglycemia in eight healthy subjects, and during hyperglycemia in five dysregulated diabetic patients. The results for 282 whole blood samples were compared to those of our routine method, which measures the glucose concentration in whole blood. The correlation was: y = 1.05.x - 0.05 mmol/L, r = 0.99. The glucose electrode measured a glucose concentration of 10.5 mmol/L +- 0.49 mmol/L (between-day imprecision) in a control serum (glucose 10.0 mmol/L). The glucose electrode supposedly responds to the activity of glucose that equals the molality (mmol glucose per kg water). The ratio of results with the glucose electrode and our routine method was lower than the expected ratio between water concentration in calibrator and whole blood, which is 1.18. A steep gradient from blood sample to glucose electrode, depending on the diffusion coefficient and hematocrit might explain the discrepancy. PMID- 1292517 TI - Sensor arrays based on biological systems. PMID- 1292518 TI - In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue. AB - Cleanroom processing techniques have been used to mass-produce flexible, electroenzymatic glucose sensors designed for implantation in subcutaneous tissue. In vitro characterization studies have shown the sensor's performance to be acceptable. Initial in vivo studies were conducted with the sensor implanted in the subcutaneous tissue of rabbits. Sensors implanted in the subcutaneous tissue of normal human subjects showed an excellent correlation between glucose concentrations measured by the sensor and capillary finger sticks measured with a commercial analyzer. PMID- 1292519 TI - Fluorescent fibre-optic immunosensing system based on complement lysis of liposome containing carboxyfluorescein. AB - A novel type of fibre-optic immunosensing system has been developed. Agar gel immobilized liposomes containing carboxyfluorescein were attached to the tip of an optical fibre. Complement-mediated immunolysis of the liposome was fluorometrically detected through the fibre. By using dinitrophenyl (DNP) hapten loaded liposomes, concentrations as low as 500-fold diluted anti-DNP antibody and 0.76 CH50 ml-1 of complement were detected. PMID- 1292520 TI - Implementation of a thermal biosensor in a process environment: on-line monitoring of penicillin V in production-scale fermentations. AB - The production of penicillin V was monitored in 0.5 m3 and 160 m3 bioreactors. The thermal biosensor was an enzyme thermistor modified for split-flow analysis. The heat signal generated in the enzyme column was corrected for any nonspecific heat with the use of an identical but inactive reference column. The on-line monitoring was performed in the fermentation pilot plant and in a fermentation plant of Novo Nordisk A/S. Immobilized beta-lactamase was used to monitor three consecutive 0.5 m3 penicillin fermentations. Broth samples were continuously filtered through a tangential flow filtration unit in a sterile external loop. The on-line penicillin V values were 10% higher than those obtained by off-line HPLC analysis. Alternatively a polypropylene filtration probe was inserted into a 160 m3 bioreactor and samples were withdrawn at 0.5 ml/min. The same experiments were repeated with purified and immobilized penicillin V acylase. The on-line penicillin V values obtained with this enzyme correlated very well with those from HPLC analysis. The on-line monitoring was controlled and analysed by a software program written in Labtech Notebook. PMID- 1292521 TI - Covalent binding of urease on ammonium-selective potentiometric membranes. AB - As part of the development of disposable urea bioselective probes, the covalent binding of urease on ammonium-selective potentiometric membranes has been assessed. Nonactin/bis(1-butylpentyl)adipate/poly(vinylchloride) (PVC) membranes, directly applied to an internal solid contact (conductive epoxy-graphite composite), has been used as a support for covalent immobilization of urease. Two types of all-solid-state construction process have been assayed: thin layers of cellulose acetate (CA) were coated on the PVC ammonium-selective membranes (type 1) and blends of PVC and CA at various ratios were used as ammonium-selective membrane matrices (type 2). Urease was covalently attached to CA via aldehyde groups. These groups were created on the polysaccharide with sodium periodate to which the enzyme was immobilized through a spacer (hexamethylenediamine). The viability of both types of probe for the determination of ammonium ions was assessed after each step of the activation process. Results indicated that type 2 potentiometric probes are altered after the treatment with sodium periodate. Good results were obtained with type 1 probes. Their dynamic concentration range of response to urea was from 2 x 10(-5) to 0.01 M with a sensibility of 50 mV/decade. PMID- 1292522 TI - Sulotroban selectively inhibits thromboxane-receptor-mediated responses in the peripheral vascular bed of the cat. AB - The effects of Sulotroban (BM 13.177, SK&F 95587) were investigated under conditions of controlled blood flow in the hindquarters and mesenteric vascular beds of the cat. Injections of the thromboxane (TX) A2 mimics, U46619 and U44069, caused dose-related increases in perfusion pressure. After administration of SK&F 95587, vasoconstrictor responses to the TXA2 mimics were reduced significantly, and the dose-response curves were shifted to the right in a parallel fashion. Responses to norepinephrine, phenylephrine, tyramine, endothelin-1, angiotensin II, BAY K8644, acetylcholine, sodium nitroprusside, isoproterenol, lemakalim, prostaglandin (PG) E1, and PGF2 alpha, agents which alter vascular resistance by a variety of mechanisms, were not changed by the TXA2 receptor antagonist. However, SK&F 95587 reduced mesenteric vasoconstrictor responses to PGD2. Results of the present study indicate that SK&F 95587 blocks TX-receptor-mediated responses in the hindquarters circulation of the cat in a competitive and selective manner and reduces mesenteric vascular responses to the TXA2 mimics, as well as PGD2. These data suggest that this antagonist would be useful in studies on the role of TXA2 in physiologic and pathophysiologic processes in the systemic vascular bed of the cat. PMID- 1292523 TI - Role of eicosanoids in rat aortic ring response to agonists and acetylcholine with special reference to the biphasic effects of prostacyclin. AB - To examine the role of prostanoid release during vascular contraction and endothelium-dependent relaxation, isolated rat thoracic aortic rings were contracted with norepinephrine (NE) or the thromboxane analog U46,619 and then exposed to acetylcholine (ACh). Pretreatment of aortic rings with the cyclooxygenase inhibitor indomethacin decreased (P < 0.05) NE and U46,619-induced contraction. Subsequent ACh-mediated relaxation was also reduced (P < 0.05) in the indomethacin-treated rings. These observations suggest that cyclooxygenase products participate in the rat aortic contractile response to agonists and the relaxation response to ACh. Since prostacyclin has been claimed to contract rat aortic rings, other sets of aortic rings were precontracted to different preloads with NE and then exposed to varying concentrations to prostacyclin (0.02 to 4000 ng/ml). Prostacyclin in modest amounts uniformly decreased aortic ring tension, while greater (> or = 2000 ng/ml) concentrations resulted in a modest contractile response. Prostacyclin per se had minimal contractile effect on quiescent rat aortic rings, but only at unphysiological concentrations. These observations indicate that the primary effect of prostacyclin on rat aortic rings is vasorelaxation, but very high, unphysiological concentrations may result in contraction. PMID- 1292524 TI - Suggested mechanism for the formation of 15-hydroxyeicosatrienoic acid by rat epidermal microsomes. AB - We have previously demonstrated that rat epidermal microsomes NADPH-dependently convert 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) into 15 hydroxy-5,8,11-eicosatrienoic acid (15-HETrE). The present study examines the mechanism of this reductive conversion. Rat epidermal microsomes were incubated with [1-14C]15-HPETE in the presence and absence of NADPH. Major reaction products were purified by high performance liquid chromatography (HPLC) and analyzed by gas chromatography-mass spectrometry (GC-MS), UV spectroscopy and/or cochromatography with standard products. In the presence of NADPH, 15-HPETE was transformed to 13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid (13-HEpETrE), 15(S)-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), 15-keto-5,8,11 eicosatrienoic acid (15-KETrE) and 15-hydroxy-5,8,11-eicosatrienoic acid (15 HETrE). In the absence of NADPH, the microsomes reacted with 15-HPETE to form 13 HEpETrE, 15-keto-5,8,11,13-eicosatetraenoic acid (15-KETE) and 15-HETE. Furthermore, when supplemented with NADPH, epidermal microsomes converted 15-KETE to 15-KETrE, which was subsequently reduced to 15-HETrE. These data suggest that rat epidermal microsomes are capable of metabolizing 15-HPETE to 15-HETrE via the following reaction steps: conversion of HPETE to KETE, NADPH-dependent double bond saturation in KETE to KETrE and keto-reduction of the latter compound to HETrE. PMID- 1292525 TI - Thromboxane B2 urinary metabolites in patients undergoing cardiopulmonary bypass. AB - The urinary excretion of selected markers for renal injury and thromboxane metabolites was studied in 16 patients undergoing cardiopulmonary bypass (CPB). Excretion of both tubular and glomerular markers sharply increased on day 1 after CPB and remained elevated throughout the observation period (five days). Immunoreactive thromboxane B2 (i-TXB2, mainly reflecting 2,3-dinor-TXB2) and immunoreactive 11-keto-thromboxane B2 (i-11-keto-TXB2) were measured by direct enzyme immunoassays. TXB2, 2,3-dinor-TXB2 and 11-keto-TXB2 were also measured in selected samples by GC-MS. Urinary excretion rates of both i-TXB2 and i-11-keto TXB2 markedly increased on day 1 after surgery and decreased thereafter. Following CPB, excretion rates of 2,3-dinor-TXB2 and TXB2 displayed parallel changes, suggesting that in these patients most urinary TXB2 derives from blood platelets rather than the kidney. Taken together, our observations do not support the hypothesis that acute renal injury observed after CPB is caused by exaggerated thromboxane biosynthesis in the kidney. PMID- 1292526 TI - Epicardial versus endocardial "in mirror" changes in prostaglandin synthesis after short periods of ischemia and reperfusion. AB - Cardiac ischemia and reperfusion are associated with increased prostaglandin levels in the coronary venous effluent. This study implemented an in vivo-in vitro technique to investigate regional alterations in heart tissue PGE2 and PGF2 alpha de novo production. Canine endocardial and epicardial explants were incubated following 5 min regional ischemia, or 5 min ischemia with 10 min reperfusion, induced in vivo in two groups of animals (n = 10 and 6, respectively). Ischemia produced a significant upsurge in endocardial but not in epicardial prostaglandin synthesis as compared with the non-ischemic zone: 7.6 +/ 0.7 versus 4.5 +/- 0.5 pg/mg tissue per h in PGE2 (P < 0.001) and 8.8 +/- 1.2 versus 6.8 +/- 1.2 pg/mg per h PGF2 alpha (P < 0.01). Following reperfusion, PGE2 was higher in the apparently normal than in the affected endocardium (5.8 +/- 0.6 versus 4.4 +/- 0.5 pg/mg per h, P < 0.05). Opposite changes occurred in the reperfused epicardium: 8.2 + 0.9 versus 4.9 +/- 0.7 pg/mg per h PGE2 (P < 0.01) and 11.1 +/- 0.9 versus 6.0 +/- 0.6 pg/mg per h PGF2 alpha (P < 0.001), for the reperfused as compared to the "normal" region, respectively. Our findings imply that the left ventricular wall is not homogeneous in its eicosanoid response to ischemia and reperfusion. "In mirror" changes were found between endocardium end epicardium and between the injured and the apparently normal regions. PMID- 1292527 TI - Metabolism of absorbed glucose in mouse jejunum: influence of arachidonic acid, non-steroidal anti-inflammatory drugs and eicosanoids. AB - The involvement of arachidonic acid and eicosanoids in glucose absorption and metabolism was investigated in isolated mouse jejunum. Characteristics of glucose absorption and its metabolic fate are reported. Reduction in the dietary precursor of arachidonic acid, linoleic acid, and inhibition of phospholipid hydrolysis with mepacrine reduced glucose absorption with no effect on metabolism, although mepacrine increased the proportion of luminal to serosal lactate release. Bradykinin and n-FMLP enhanced metabolism by 2.1- and 2.4-fold, respectively, both reducing the percentage of metabolised glucose converted to lactate, while neither influenced absorption. Both indomethacin and NDGA decreased absorption and enhanced metabolism. The percentage of metabolised glucose converted to lactate decreased and the ratio of luminal to serosal lactate release was unchanged. In the absence of inhibitors, PGE2 (5 microM) decreased absorption by 28%, metabolism by 24% and total lactate production by 32% and LTB4 (20 nM) increased only absorption by 32%. PGE2 release into the perfusates was predominantly serosal (1-10 nM) and was inhibited by indomethacin. PGE2 could not reverse the indomethacin-induced decrease in absorption, but reversed the enhancement of metabolism by 89% and total lactate production by 60%. In conclusion, while the specificity of the drug-related absorptive effects remain unclear, alterations in the utilisation of the absorbed glucose via drug induced changes in arachidonic acid synthesis and metabolism are apparent. Furthermore, exogenous PGE2 may protect against the effects of indomethacin and itself reduces active glucose absorption, the metabolism of the absorbed glucose and the amount of lactate formed. PMID- 1292528 TI - Loss of cytosolic 15-lipoxygenase activity in A23187-stimulated human leukocytes: involvement of a translocation process? AB - We focused our study on the subcellular redistribution of 15-lipoxygenase in human leukocytes challenged with A23187 and arachidonic acid (AA). We found that in cytosolic fractions of stimulated cells the 15-lipoxygenase (15-LO) activity, measured as 15-HETE, was 65% less than in controls. However, no activity was found in cell membranes. This effect was complete within 2 min of incubation and was correlated in a dose dependent manner to exogenously added AA. No significant difference in cytosolic distribution of 15-LO activity was observed when cells were stimulated in presence of various concentrations of Ca++. Immunoblot analysis showed that the loss of cytosolic 15-LO activity registered after challenging with A23187 was associated with a concomitant loss of the enzyme content in the cytosol, suggesting the possibility of a translocation process. Neither the 15-LO activity nor the enzyme was, however, found in the cell membrane under our present experimental conditions. But, addition of protease inhibitors showed a slight increase of 15-LO activity in the membrane fraction. Despite the small effect, this may indicate a translocation of 15-LO following challenge of human leukocytes with A23187. PMID- 1292529 TI - Diet-induced atherosclerosis in rabbits alters vascular prostacyclin release. AB - Atherosclerosis is complicated by thrombosis and it has been suggested that a decreased prostacyclin and/or an increased thromboxane release from the vascular wall could play a part in this process. There are few reports dealing with determinations of prostanoid release from physiologically perfused normal and atherosclerotic vessel walls or from perfused atherosclerotic hearts. Therefore, fourteen rabbits were given 2% cholesterol added to the diet for 26 weeks, which led to atherosclerosis, verified by scanning electron microscopy. Five animals died, and in the surviving nine, as well as from ten healthy rabbits, the aorta was excised. The vessels were perfused with pulsatile flow at physiologic pressure five times for fifteen minutes with the addition of arachidonic acid to the last perfusate. Prostacyclin and thromboxane were determined as their stable degradation products 6-keto-PGF1 alpha and TxB2 by radio-immuno assay. Atherosclerotic and normal animals had the same initial release of prostacyclin but in the atherosclerotic animals the release did not decline with time as it did in the normal animals. The response to arachidonic acid was also higher in the atherosclerotic group. The release of thromboxane was not altered in the atherosclerotic group compared to the control group. It is concluded that prostacyclin release from aortas is altered in rabbits with diet-induced atherosclerosis compared to normal rabbit aortas, but that vascular thromboxane production is not. PMID- 1292530 TI - [Peritoneal dialysis in the chick embryo with gastroschisis]. AB - The ever increasing possibilities of prenatal diagnosis and intra-uterine treatment of malformations has created the need for simple and reproducible experimental models on which to build a better knowledge of the biology of the abnormal fetus. Using our own model of experimental gastroschisis (GX) in the chick embryo, we have undertaken to study whether transperitoneal exchanges of water and solutes take place after prolonged visceral exposure to the mixture of amniotic and allantoic fluids which has a greater content in Potassium, Urea, and Proteins and less sodium, chloride and glucose than fetal blood. After surgical evisceration of bowel on the 14th day, incubation was resumed until the 19th day and the embryos were then recovered for weighing and for blood sampling biochemical analysis. The chicks with GX had significantly increased serum Potassium and minimally increased Urea whereas Sodium and Chloride were moderately decreased. Our data confirm that a real peritoneal dialysis with transperitoneal exchange of water and solutes between extraembryonal fluids and the fetal internal environment does indeed take place in this model. PMID- 1292531 TI - [Pulmonary surfactant in experimental congenital diaphragmatic hernia]. AB - This paper examines the amounts of tensoactive phospholipids in the lung tissue of rat fetuses treated with Nitrofen (TOK) and in control animals. The herbicide led to congenital diaphragmatic hernia (CDH) in some fetuses and to pulmonary hypoplasia (PH) in all. The amounts of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) per gram of fresh lung tissue were significantly increased in comparison with the control animals, those of phosphatidylserine (PS) and sphingomyelin (SM) were also increased, but not significantly. Fetuses with HP alone had intermediate values. These findings are in agreement with our previous demonstration of an excess of type II pneumocytes in this model, and point to the existence of some trouble of the secretion or release of surfactant in it; although they do no clarify whether the amount of alveolar surfactant is in fact decreased. PMID- 1292532 TI - [Skin graft protection by treatment of recipients with ultraviolet irradiated fragments of the donor spleen]. AB - We have tested de possible protective effects of UVA radiated spleen fragments upon simultaneous skin allografts in 84 rats. Under these circumstances skin graft rejection was less evident with a 20 day graft disappearance rate of 46.87% rate in the treated series, that compares favourably with a 80% in the control series. This study shows a parallel increase in the mean survival time of skin grafts in treated specimens. The figures being 19.8 days in the treated series against 12.9 days in untreated controls. Spleen implants are finally shown to produce a healing stimulus in the skin graft zone. These differences are statistically significant. PMID- 1292533 TI - [Protocol for the treatment of hypertrophic cicatrix with silastic gel. First results]. AB - Functional limitation and scarring use to be common sequelaes of a burns injury in children. We report our initial experience with silicone gel (silastic gel shetting) in the treatment of 15 children with hypertrophic scars, without success to other alternatives therapies. Improvements in texture, colour and height of the lesion were noted in all cases. PMID- 1292534 TI - [Urodynamic diagnosis and treatment in neurogenic bladder dysfunction]. AB - A group of 55 patients (28M,27F) with neurogenic bladder dysfunction was studied. Patient age ranged from 1m. to 20 years (mean age 9.1 years). Most of the patients had neurogenic bladder secondary myelomeningocele (70%). The urodynamic investigations demonstrated detrusor hyperreflexia in 50 (poor compliance in 28p) detrusor arreflexia in 3 and normal bladder in 2. Six patients hadn't incontinence and didn't need treatment. The rest (49p), couldn't be dry more than 2 hours. After treatment (anticholinergic, alpha adrenergic agonist, alpha-betha adrenergic agonist, I. C. and bladder augmentation), the continence was improved satisfactorily in 38 patients (77.5%). In conclusion, we think that early treatment from neonatal period, supported with urodynamic studies may prevent lon term renal damage and most patients with neurogenic bladder do not require surgical intervention to improve continence because it can be controlled satisfactorily by other means. PMID- 1292535 TI - [Role of echography in septic arthritis of the hip in the newborn]. AB - Pyogenic arthritis of the hip in neonates remains a serious problem. The sequelae of delay in diagnosis and treatment can be crippling. Five hips, in four neonates, with a presumed diagnosis of septic arthritis were examined with ultrasonography. In two hips ultrasonography found intracapsular effusion. In the remaining three hips there were no pathological findings. In the two hips with joint effusion an arthrotomy was performed, dislodging pus in both cases. Follow up radiographs and ultrasonographies of the five hips showed normal joint anatomy. In neonates, ultrasonography provides an early and reliable evaluation of hips in which septic arthritis is suspected. PMID- 1292536 TI - [Thymus in posterior mediastinum]. AB - It is presented the clinical case of a mass of posterior mediastinum with diagnostic by C.T.Scan, and ratified by Pathologic Anatomy, as posterior prolongation of thymus. Comments of the importance of the diagnostic by image and the rarity of this entity are made. PMID- 1292537 TI - [Solitary hepatic cyst. Presentation of a case diagnosed in neonatal period]. AB - We reported one case of hepatic solitary cyst, in an infant seven days old. The precocious diagnostic was supported by the presence of an abdominal cyst mass in prenatal period. Different diagnostic and therapeutic consideration are made. PMID- 1292539 TI - [Idiopathic perforation of the colon with simultaneous acute appendicitis in a newborn. Presentation of a case]. AB - We report a case of a three days old male newborn who suffered several apnea crisis. Radiologic studies revealed a pneumoperitoneum. Laparotomy proved it was caused by two intestinal perforations in the ascending colon. Histologic study showed a concomitant suppurated acute appendicitis. We discuss the case features, its possible etiopathogeny and the most frequent clinical aspects and treatment of intestinal perforation at this age. PMID- 1292538 TI - [Appendicular carcinoid tumor in childhood]. AB - Apendicular Carcinoid tumors are very infrequent, being lower than 0.1% of the appendicectomies carried out. We report on the case of a 13 year-old girl, with Acute Appendicitis picture. The appendix was removed and the histological study revealed the presence of the carcinoid tumor with a diameter of a 6 mm. Where non invasive treatment was decided on, and at present, after two years follow-up, there has been no recurrence. PMID- 1292540 TI - [Ureteral valve associated with pyeloureteral stenosis]. AB - We report a case of ureteric valve associated with pyeloureteral obstruction, exhibited as fistula after pyeloplasty. We analyst different features of ureteric valves: anatomical, location, symptoms and associated congenital anomalies. The writer consider necessary to achieve the sounding of ureteral stretch during the operation of pyeloplasty. PMID- 1292541 TI - [Avoidable complications in the management of a patient with an artificial urinary sphincter]. AB - All the patients who underwent implantation of an artificial urinary sphincter can have three types of complications: those coming from the own patient, mechanical complications and other aleatory ones. J. L. C. A., a 13-year-old boy with secondary neurogenic bladder, received the implantation of a model AUS 800 artificial urinary sphincter for urinary incontinence. After 15 months without problems, he was admitted in our hospital with pump erosion in the scrotum. He was operated on and the pump system was preserved. No plain roentgenograms were made neither before nor after surgical procedure. However, the balloon pressure reservoir was not seen in a control pielogram performed before his discharge from the hospital. Three months later the entire device should be removed because of infection. In the operation a cut off tube was found. A new artificial urinary sphincter was reimplanted and the cuff was placed around the bulbous urethra one year later. Retrospective analysis of this case can help to review the possible complications and their management. PMID- 1292542 TI - Technologic advances in diagnostic radiology. AB - Technologic advances in radiographic equipment and procedures for four different areas of diagnostic radiology are reviewed: bone mineral assessments, musculoskeletal imaging, mammography, and chest imaging. For bone mineral assessments the accuracy and precision obtained using single- and dual-energy photon absorptiometry, dual-energy x-ray absorptiometry, and quantitative CT are summarized. Various digital systems employed in musculoskeletal imaging are reviewed. In mammography, papers related to accreditation and research interests are highlighted. The use of photo-simulated phosphor plates and scanned equalization radiographic systems for chest imaging are discussed. Finally advances in radiographic film processing are noted. PMID- 1292543 TI - Imaging of degenerative disk diseases. AB - This review provides a new understanding of the areas of disk anatomy, degeneration, herniation, and lumbar canal stenosis. It discusses new findings on calcified disks, disk imaging, intraspinal synovial cysts and even intraspinal pigmented villonodular synovitis. Special attention has been given to percutaneous therapeutic procedures and the postoperative spine. PMID- 1292544 TI - Osteoporosis and bone mineral densitometry. AB - Osteoporosis is a common cause of vertebral and hip fractures and although their occurrence depends on a variety of factors, bone mineral density (BMD) is the most important determinant. Methods of measuring BMD are therefore pertinent to identify individuals with reduced bone mass and at increased risk of fracture, and current techniques provide accurate and precise BMD measurements with low radiation dose. The methods most widely used are single photon absorptiometry; dual photon absorptiometry, which has been replaced by dual energy x-ray absorptiometry; and quantitative CT. Dual energy x-ray absorptiometry permits BMD measurement in the lumbar spine, femoral neck, forearm, and whole body. Bone strength is also related to trabecular width and arrangement. The newer techniques of broadband ultrasound attenuation and MR imaging (T2*) offer potential for investigating both trabecular bone mass and structure, as does high resolution CT. These methods provide powerful tools for the study of the skeleton in health and disease and have established roles in appropriate clinical circumstances. Although BMD measurement can provide an estimate of fracture risk, there are limitations to fracture prediction in an individual subject, but efforts are being made to improve the discriminatory and predictive aspects of BMD. PMID- 1292545 TI - Imaging of the postoperative spine. AB - In the current literature on the imaging modalities of the spine, several papers deal with the diagnostic evaluation of the postoperative spine. Particular attention is focused on the use of MR imaging in evaluating the postoperative spine in symptomatic and asymptomatic patients. Other papers discuss application of different radiologic modalities such as conventional tomography, CT, sonography, and scintigraphy. The effectiveness of various imaging techniques in evaluating the postsurgical changes in the spine is the subject of this review. PMID- 1292547 TI - Musculoskeletal radiology. PMID- 1292546 TI - Radiology of Paget's disease. AB - A review of Paget's disease produces few surprises; however, several good articles have recently been published on its appearance, on MR imaging, sarcomatous degeneration, and the disease-related occurrence of multicentric giant-cell tumors. One recent paper illustrated the possible progression of fibrous dysplasia occurring in the skull after adolescence, a finding that does not occur elsewhere. An excellent review article on the normal and abnormal calcaneus is reviewed, and two brief reports on skeletal angiomatosis are discussed. Condensing osteitis of the clavicle is well described in one article that proves it to be an entity distinct from chronic recurrent multifocal osteomyelitis of the clavicle seen in children. Finally, a number of articles on congenital spinal anomalies are reviewed. PMID- 1292548 TI - Magnetic resonance imaging of bone marrow. AB - The development of MR imaging has been a great advance in the imaging of bone marrow disorders. MR imaging exhibits excellent soft-tissue contrast and therefore has a greater sensitivity for marrow disease than did previously available modalities. This article reviews the normal morphology and appearance of bone marrow, describes the MR appearance of normal bone marrow, and discusses the MR findings associated with various marrow disorders. PMID- 1292549 TI - Imaging of bone tumors. AB - In the recent literature on benign bone tumors, papers have highlighted the atypical appearances of intracapsular osteoid osteoma, the characteristic (yet not pathognomonic) feature of fluid-fluid levels on CT and MR imaging of aneurysmal bone cysts, the difficulties of MR imaging of giant cell tumors laden with hemosiderin following intratumoral hemorrhage, and the reliability of ultrasound in measuring the thickness of the cartilage cap in chondroid lesions. MR imaging remains preeminent in the staging of musculoskeletal tumors, although, as yet, there has been only limited success in using this modality for tissue characterization. One study has described certain distinctive patterns on MR associated with different histologies. In particular, peritumoral edema was only found in malignant bone tumors and giant cell tumors. Subjective MR criteria would appear not to be helpful in identifying osteosarcomas patients who are good responders to chemotherapy. Intra-arterial chemotherapy for osteosarcoma of the lower limb may be complicated by infarction of the distal femur, which on MR imaging should not be mistaken for metastatic or transarticular tumor spread. PMID- 1292550 TI - Imaging of soft tissue tumors. AB - The evaluation of many soft tissue lesions remains a diagnostic dilemma for both the radiologist and the clinician. In recent years MR imaging has emerged as the modality of choice for the assessment of soft tissue tumors, with well-documented advantages over CT and other imaging techniques. PMID- 1292551 TI - Muscle, tendon, and ligament evaluation. AB - Magnetic resonance imaging is the technique of choice for soft tissue evaluation. Muscle injuries occurring during physical activities are very frequent and are very well appreciated by MR imaging. Associated with 31P spectroscopy, MR imaging allows better understanding of physiopathologic phenomena and inflammatory lesions. An early and correct diagnosis is possible using MR imaging in cases of soft tissue pseudotumors, such as myositis ossificans. The quadriceps and Achilles tendons, which are superficial and thick, can be well evaluated using ultrasonography. Nevertheless, MR imaging is superior for deeply situated tendons and ligaments of the knee and ankle. PMID- 1292552 TI - Imaging of the skeleton and soft tissues in children. AB - Sonographic applications to osteomyelitis, myositis ossificans, tropic pyomyositis, child abuse, synovitis, and slipped capital femoral epiphyses; MR imaging (including gadolinium-enhanced MR scans) in osteomyelitis, the normal and abnormal physis, physeal bars, normal marrow, Gaucher disease, cancer, dysplasia epiphysealis hemimelica, myositis, tenosynovitis, arthritis, and clubfoot; nuclear imaging in osteomyelitis, tibia valga, limp, and unexplained lower extremity pain; and CT in osteomyelitis, are reviewed. Routine long-bone radiography for patients with congenital syphilis is not recommended. Tibia valga after fracture has not been fully explained; tibia valga also follows treatment of renal failure. Nonsupracondylar humerus fractures in infants and femoral shaft fractures in the first year of life may suggest child abuse. PMID- 1292553 TI - Radionuclide investigation of osteomyelitis. AB - The diagnosis of osteomyelitis in the presence of fracture and orthopedic appliances and in the diabetic foot can be a formidable challenge to radionuclide imaging. Radiophosphate is highly sensitive in detecting bone disease, but of low specificity; to improve specificity it must be complemented by 67Ga or radiolabeled leukocytes. These latter agents are not without limitations, and the search for new agents and novel imaging strategies continues. The relative roles of nuclear medicine and MR imaging are coming into focus, and a diagnostic algorithm based on the shortcomings of both methods is suggested. PMID- 1292554 TI - Magnetic resonance imaging of the shoulder joint. AB - Because the shoulder is the most mobile joint in the body, it is naturally predisposed to several disorders. The most commonly encountered disorders requiring diagnostic imaging are rotator cuff disease and glenohumeral instability. Plain film radiography and arthrography have for many years been the mainstays of shoulder imaging. CT added a third dimension to shoulder imaging, improving its sensitivity with respect to glenoid labral pathology. Ultrasonography of the rotator cuff showed early promise in noninvasive evaluation of cuff tears, but it did not gain universal acceptance because of various negative factors, including inadequate visualization of the cuff, poor results regarding partial tears, and most importantly, operator dependency. The development of MR imaging afforded the radiologist improved comprehensive visualization of the shoulder joint in a noninvasive manner. PMID- 1292555 TI - Magnetic resonance imaging of the knee: evaluation of meniscal disease. AB - The advent of MR imaging in musculoskeletal radiology, coupled with advances in the past decade in the treatment of knee disorders, has fueled an explosion of interest in MR imaging of the knee. Evaluation of meniscal pathology has been central to this development. The accuracy of MR imaging in the diagnosis of meniscal tears is now well established; attention has more recently been focused on the prevalence, natural history, and clinical significance of other intrameniscal signal abnormalities, as well as on the postoperative meniscus. Nonmeniscal knee disorders that may clinically mimic meniscal lesions are also reliably diagnosed with MR imaging. Technical advances in pulse sequences allow knee imaging with enhanced accuracy and efficiency. PMID- 1292556 TI - Imaging pediatric hip disorders and residual dysplasia of adult hips. AB - The application of newer imaging modalities such as ultrasound, CT, and MR imaging has made a major contribution to the understanding of pediatric hip disorders. Multiplanar imaging has been a major advancement in the depiction of the complex hip joint anatomy. Direct visualization of cartilage in the immature joint is now possible with MR imaging. Sophisticated computer software programs allow three-dimensional reconstruction of the joint from CT and MR data. Manipulation of three-dimensional images allows preoperative simulation of proposed surgical reorientation of hips with deformity resulting from dysplasia and Legg-Calve-Perthes disease. PMID- 1292557 TI - Evaluation of joint prostheses and orthopedic appliances. AB - Several recent articles describe imaging evaluation after joint replacement surgery. The following articles about total hip and knee replacement and silicone rubber prostheses are highlighted because they offer new observations or review typical problems after joint revision surgery. PMID- 1292558 TI - Imaging of the normal spine, developmental anomalies, and trauma of the spine and extremities. AB - Many significant papers in the current literature have considered the spectrum of developmental and traumatic alterations in the spine. The increasing role of MR and CT imaging is stressed as well as the continued importance of conventional radiography. The distinguishing features and pathology of developmental anomalies and traumatic injuries and the importance of accurate and complete diagnosis are discussed. This review includes articles that emphasize imaging of the normal spine, congenital anomalies, and trauma of the spine and extremities. PMID- 1292559 TI - [Hernia surgery today]. PMID- 1292560 TI - [The functional recovery of the internal anal sphincter and the restoration of continence after rectopexy for rectal prolapse]. AB - Eleven patients with full thickness rectal prolapse underwent ambulatory fine wire electromyography (EMG) of the internal anal sphincter (IAS), external anal sphincter and puborectalis muscle, and anorectal manometry using a computerised system. Examinations were performed preoperatively and at 3 months following rectopexy. The median preoperative IAS EMG frequency was 0.21 Hz (range = 0.05 0.30) and the median preoperative resting anal pressure (RAP) was 13 cmH2O (range = 2-84 cmH2O). A significant improvement in the IAS EMG frequency (median = 0.31 Hz; 0.23-0.47 Hz; p < 0.02) and RAP (median = 30 cmH2O; 20-84 cmH2O; p < 0.01) was noted post-rectopexy but these parameters remained significantly different from a group of normal controls (median IAS EMG frequency = 0.48 Hz; 0.25-0.61 Hz; median RAP = 76 cmH2O; 22-120 cmH2O). We suggest that repair of the prolapse allows the IAS to recover by removing the cause of persistent recto-anal inhibition. PMID- 1292561 TI - [The complications of pulmonary resection surgery: the experience of 200 consecutive cases]. AB - Postoperative complications observed in 200 patients after pulmonary resection (66 pneumonectomies--30%, 106 lobectomies--53% and 28 wedge resections--17%) are presented. Surgical operations were carried out in 86% of cases for cancer, in 16% for benign lesions. Major complications were: lobar atelectasis, bronchopneumonia, pulmonary embolism, respiratory insufficiency, bronchial fistula, ventricular tachyarrhythmia, altogether they concerned 21% of the cases. Their incidence was not significantly influenced by the extension of resection (the latter, on the contrary, influenced postoperative mortality as much as 4.5% after pneumonectomy, 2.8% after lobectomy and 0% after wedge resection), age of patients under or over 70 years, functional respiratory reserve, or associated cardiovascular diseases. On the contrary, the advanced stage of disease in neoplastic patients was significant for major complications. An adequate monitoring of minor respiratory and cardiac complications is recommended to reduce the incidence of major ones and their control when present. In authors' experience, in fact, postoperative mortality was overall 3% following such behaviour. PMID- 1292562 TI - [Extensive resections in rectal carcinoma. Our experiences]. AB - The authors review their experience in the surgical management of rectal cancer. They analyze rectal malignancies and their recurrences from natural history to surgical strategies and survival rates. In particular, the need to perform extended operations in order to offer patients a better prognosis is discussed. PMID- 1292563 TI - [Hepatic cystadenoma: a case report]. AB - Hepatic cystadenoma is a rare tumor arising from the biliary system. Although ultrasound and CT scan show peculiar features, diagnosis is not easy preoperatively. Because of the unreliable natural history of cystadenoma, total excision of the neoplasm by hepatic resection seems to be the treatment of choice. A case of benign cystadenoma treated by minor liver resection is reported. PMID- 1292564 TI - [2 cases of chylothorax during total parenteral nutrition: the etiopathogenetic considerations]. AB - The authors report the onset of bilateral chylothorax during postoperative total parenteral nutrition. They underline the peculiar origin of the complication. Therefore, attention is payed to the possible pathogenic causes. The overload of fluids, in the elderly with minimal functional reserves, may increase central blood pressure, so to adversely affect lymphatic drainage causing chylothorax. PMID- 1292565 TI - [The osseous location of echinococcal cysts: comments on a clinical case]. AB - Primary bone location of hydatid disease is extremely rare. The clinical case herein reported represents a primitive bone location of echinococcus in the ileal and sacral area. The aspecific symptoms did not allow for a preoperative diagnosis. The latter was possible only after a CT scan performed for other reasons. The patient underwent a CT scan and MIR which showed a diffuse involvement of the ilium and sacrum along with the presence of two cysts (anterior and posterior). Surgery was performed through an anterolateral extraperitoneal and posterior access in the gluteal region. Asportation "en bloc" of the cysts was not possible. Therefore, they were opened, aspirated and washed with hypertonic solution (33% NaCl). Following surgery Albendazole was prescribed to the patient. At 22 days from surgery, a CT scan confirmed the disappearance of the cysts along with the presence of bone lesions. PMID- 1292566 TI - [The surgical treatment of laterocervical adenopathies due to malignant cervicofacial tumors]. AB - Head and neck malignant tumors show a high tendency to spread to cervical lymph nodes. Therefore, surgical approach to these neoplasms is primary tumor exeresis associated with functional or radical neck dissection, unilaterally or bilaterally at the same time, in relation to T site and N stage. In this paper the validity of such approaches is evaluated by correlating clinical and histopathologic N involvement in 168 patients with head and neck malignancies, observed in a 5-year period (1986-1990), and submitted to radical (65 pts.) and functional (198 pts.) neck dissection. The histopathologic findings showed 31 patients (14.7%) with N0+ (false negatives). The incidence of occult latero cervical metastases confirms the importance of elective functional neck dissections in N0 patients with head and neck malignant tumors even though the risk of performing many unnecessary surgical procedures may be considerable (180 cases out of 211 in the Authors experience). Rare false positives (overall 4 cases) did not represent a significant clinical problem while N3 showed massive neoplastic invasion with extracapsular spread. PMID- 1292567 TI - [Cholecystectomy via video laparoscopy: the whys of a choice]. AB - The management of calculous disease of the gallbladder has undergone significant change during the last decade. Recent years have seen the development of alternative methods for the treatment of biliary stones including dissolution therapy, endoscopic and percutaneous extraction, extracorporeal shock wave lithotripsy. Yet, despite these technologic advances, most surgeons have continued to consider cholecystectomy the safest, most effective and the only curative procedure. Open cholecystectomy, performed in the same fashion for more than a century has demonstrated low morbidity and minimal mortality rates. However, the operation does incur sizable expense in terms of hospitalization, cosmetic appearance and time lost from work. Laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy. The authors report their experience of laparoscopic cholecystectomy performed at the Surgical Department of Montecchio Maggiore Hospital (VI). Twenty-eight patients were operated on: in all but one laparoscopic cholecystectomy was successfully completed; in one case a fistula between gallbladder and the common bile duct led to T-tube drainage insertion via a laparotomy. In one patient laparoscopic cholecystectomy was performed after an endoscopic retrograde cholangio-sphincterotomy for associated stones of the common bile duct. Mean operative time was 69 minutes (range 46 210). Morbidity and mortality were 0%; maximal hospital stay was 48 hours. These data confirm that laparoscopic cholecystectomy may be considered the treatment of choice for stone disease of the gallbladder and it should enter into the cultural and technical background of a general surgeon. PMID- 1292568 TI - [The role of magnetic resonance in the follow-up of aortofemoral prosthetic reconstructions]. AB - The authors report their experience with the use of Magnetic Resonance (MR) in the follow-up of patients undergone aortofemoral bypass or substitution procedures for aneurysmal and/or steno-occlusive lesions of the aortoiliofemoral vascular bed. Twenty-eight patients, at least 2 years from aorto-bifemoral revascularization were evaluated by means of coronal and parasagittal MR planes (mean follow up 78.9 months). One exam over 28 was found to be not diagnostic; whereas the technique showed great usefulness in the morphological and haemodynamic evaluation of each of the graft sites explored (proximal anastomosis, graft body and limbs, femoral anastomosis and periprosthetic tissues) in the remaining 27 cases. The use of this method, in spite of some setting up problems peculiar to the type of examination, according to the authors is very promising because of the chance to obtain morphological and functional data at once and because of the interesting current and future developments of this diagnostic device. PMID- 1292569 TI - [The complications of diagnostic colonoscopy]. AB - Major complications of diagnostic colonoscopy based on a series of 17.583 procedures performed from 1980 throughout 1991 are reported. No higher risk of colon perforation was registered either performing total or partial colonoscopy, for the site of perforation was in most cases the sigmoid colon. PMID- 1292570 TI - A mechanistic model for morphogenesis and regeneration of limbs and imaginal discs. AB - When an amphibian limb, cockroach leg or Drosophila imaginal disc is subjected to a surgical operation, it is capable of regenerating or duplicating certain parts. Although the structure of the regenerated tissue varies depending on the location and mass of the amputated or transplanted part, it can be predicted from a set of formal rules, called the polar coordinate model [French et al., (1976) Science 193, 969-983; Bryant et al., (1981) Science 212, 993-1002]. In the polar coordinate model, it is assumed (and experimentally proven) that the juxtaposition of normally non-adjacent cells stimulates cell proliferation locally, which implies that the underlying mechanism which gives positional values to each cell, is also responsible for the control of cell growth. Because locally activated proliferation alters the shape and size of the developmental field, the question of how to control the cell growth is the central problem in the regeneration of the limbs and imaginal discs. In this paper, I propose a possible underlying mechanism for the 'polar coordinate rules', and show how this mechanistic model explains the experimental results using computer simulation. The proposed mechanism is an extension of Turing's model (1952). In addition to the reaction-diffusion of the molecules, cell proliferation is taken into consideration. With appropriate initial conditions, the computer simulation shows that a small mass of cells grows up to form a mature limb, and that the mature limb is able to respond to surgical operations as predicted by the polar coordinate model. PMID- 1292571 TI - A Hox 3.3-lacZ transgene expressed in developing limbs. AB - We describe transgenic mouse lines that express lacZ under the control of the Hox 3.3 Promoter II. The correct anterior boundary can be fixed by 3.6 kb of promoter DNA (plus 1.6 kb of 5' transcribed sequences), both in tissues of ectodermal and mesodermal origin. The posterior border, however, is not respected, and lacZ expression continues into the tail region. One line has particularly strong graded expression in the anterior proximal limb bud. Other lines, containing a shorter promoter fragment (0.6 kb), have ectopic expression in the head region, including one line that has expression in the anterior half of the retina. Such mouse lines make it possible to molecularly distinguish cells in regions of the embryo that look otherwise identical and may be useful in studying the establishment of molecular differences in the mouse embryo. PMID- 1292572 TI - Expression of mouse PDGF-A and PDGF alpha-receptor genes during pre- and post implantation development: evidence for a developmental shift from an autocrine to a paracrine mode of action. AB - We examined the expression of platelet-derived growth factor (PDGF)-A and the PDGF alpha-receptor in pre-implantation and early post-implantation mouse embryos. At two-cell and blastocyst stages, all cells express mRNA and protein for both ligand and receptor. In contrast, early post-implantation embryos express PDGF-A chain mRNA in both embryonic ectoderm and in the ectoderm lining the ectoplacental cavity, while mRNA for PDGF alpha-receptor is localized to the mesoderm layers of both embryonic and extra-embryonic membranes. At days 3.5 and 7.5, receptors are demonstrably functional in response to exogenous PDGF-AA. We propose that chronic autostimulation of PDGF alpha-receptors occurs in pre implantation embryos, whereas, following implantation, early mesoderm development is dependent on stimulation by ectodermally produced PDGF-A. PMID- 1292573 TI - Treatment of hypertension in the elderly--the end of the story? AB - The elderly constitute a high-risk group in which the benefit of treatment of hypertension is now obvious. The initial drug should be a low-dose diuretic, followed by a beta-blocker. At present there are no data favoring the use of an ultra low-dose diuretic, such as 12.5 mg hydrochlorothiazide, unless there is coexisting prediabetes or gout. PMID- 1292574 TI - Treatment of the older hypertensive: paradigms, practices, and proofs. AB - Recent outcome trials in patients above age 60 with systolo-diastolic hypertension are reviewed. The meta-analysis suggests that antihypertensive drug therapy can decrease cardiovascular and coronary mortality in selected patients. Based on these studies it is suggested that antihypertensive drug therapy is indicated in patients between age 60 and 75 when the diastolic pressure remains above 95 mmHg after repeated measurements. A target for systolic b.p. is not definitely established but a pressure of 150 mmHg may serve as a temporary proposal. Whether uncomplicated isolated systolic hypertension in symptomless patients should be treated is still under investigation. PMID- 1292575 TI - Treatment of hypertension in the elderly--what have we learned from the recent trials? AB - Treatment of hypertension in the elderly has so far mainly been based on clinical judgment and very few large controlled trials. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP, and MRC trials. All have shown that drug treatment of hypertension in the elderly (65-85 years) with permanent diastolic hypertension or isolated systolic hypertension reduces stroke incidence. Most patients have needed combined drug treatment with diuretics and beta-blockers. When thiazide diuretics are used, serum potassium should be followed very closely and most likely amiloride should be added to the thiazide therapy, since this was done both in the STOP and the MRC trials. Since many elderly patients with hypertension suffer from other diseases that might represent contraindications to thiazide diuretics or beta-blockers, the choice of drug must be made after careful clinical evaluation. With the newer classes of antihypertensive agents (calcium antagonists, ACE inhibitors and alpha-blockers) side effects are probably seen less often, but long-term data on morbidity and mortality are still lacking. PMID- 1292576 TI - Treatment of hypertension in the elderly. AB - Treatment of hypertension in the elderly is beneficial, and benefit exceeds risk, but in some individuals it may be difficult to decrease blood pressure to goal or normotensive levels. Recent data suggest that the use of diuretics and, in some instances, beta-adrenergic inhibitors will reduce morbidity and mortality in elderly hypertensives and will probably not alter metabolic parameters to a clinically significant degree in most individuals. PMID- 1292577 TI - The case for antihypertensive drug treatment in subjects over the age of 60. AB - The already strong case for drug treatment of hypertensive patients aged over 60 has been reinforced by the reports on the SHEP, STOP, and, to a lesser extent, MRC trials. SHEP showed benefit in "isolated systolic" hypertension, mainly in relation to stroke, but with a strong trend towards also reducing myocardial infarction. SHEP demonstrated advantages from low-dose chlorthalidone, especially if hypokalemia was prevented. STOP in patients aged 70-84 at entry demonstrated a reduction in stroke and all-cause mortality but not in myocardial infarction; benefit was apparent in women as well as men. The MRC trial, in subjects over 65, many of whom had "isolated systolic" hypertension, found a reduction in stroke but not in coronary events or all-cause mortality. Extensive cross-contamination of allocated treatment groups restricted worthwhile evaluation of different drug regimens in MRC. Potential benefits from antihypertensive drug treatment in old people are substantial but are in danger of being discredited because of intemperate and inaccurate claims. PMID- 1292578 TI - Hypertension in the elderly. AB - Publication of the SHEP study (Systolic Hypertension in the Elderly Programme) leaves no doubt that isolated systolic hypertension in the elderly should be treated. There are, however, a number of important outstanding questions: (a) the mechanism of reduction of morbidity, (b) because antihypertensive therapy appears to be more effective in elderly patients than in the young, when should treatment be started in relation to progression of age?, (c) besides the blood pressure elevation, what are the exact mechanical factors responsible for degeneration of the arterial wall?, and (d) what in 1993 is the definition of hypertension? These are questions that now need to be answered. PMID- 1292579 TI - Iontophoretically enhanced transdermal delivery of an ACE inhibitor in induced hypertensive rabbits: preliminary report. AB - Both conventional direct current (DC) and pulsed-mode DC constant-current iontophoresis were used to investigate enhanced transdermal delivery of the angiotensin-converting enzyme (ACE) inhibitor captopril to rabbits with acutely induced hypertension. Passive transdermal captopril administration and pulsed DC constant-current iontophoresis of the vehicle were studied as control experimentation. Mean arterial pressure (MAP) was not significantly (p > 0.05) altered following passive transdermal delivery of captopril (n = 4) or after iontophoretic delivery of the vehicle alone (n = 4). Pressure reduction was evident within 10 minutes of iontophoretic enhancement of transdermal captopril delivery. DC mode constant-current (n = 4) iontophoretic transdermal captopril administration caused MAP to fall by 21% from a mean hypertensive level of 66 +/- 5 mmHg to a mean post-treatment level of 52 +/- 6 mmHg (p < 0.05) within 60 minutes. Pulsed DC mode constant-current (n = 4) iontophoresis of captopril caused mean MAP to fall on average by 27% from 62 +/- 6 to 45 +/- 5 mmHg (p < 0.05), also within 60 minutes. This paper provides the first report on the enhanced efficiency during iontophoretic delivery of an ACE inhibitor. We have concluded that both modes of constant-current iontophoresis of captopril offer a safe and effective means of pressure reduction in rabbits with induced hypertension and that there is no significant difference in efficacy between the two forms of enhanced delivery. These results have potential applications for enhanced transdermal delivery of ACE inhibitors in humans. PMID- 1292580 TI - Vascular relaxation to omega-3 fatty acids: comparison to sodium nitroprusside, nitroglycerin, papaverine, and D600. AB - The vasorelaxant activity of the omega-3 fatty acids--docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids--in comparison with other known vasodilators--sodium nitroprusside, nitroglycerin, papaverine, and D600--were studied in the isolated rat aorta. The relaxant responses of these vasodilators and fatty acids at concentrations of 1-100 microM were assessed in aortic rings contracted with norepinephrine (NE 10(-6) M) or with KCl (30 mM). Cyclic nucleotide enhancers (sodium nitroprusside, nitroglycerin, papaverine) were more effective in producing relaxation, regardless of the contractile mechanism, i.e., alpha adrenoceptor stimulation or depolarization. In contrast, the omega-3 fatty acids produced augmented relaxation in NE-contracted vessels. Relaxations produced by DHA (15 +/- 2% to 45 +/- 10%) were similar to D600 (16 +/- 2% to 60 +/- 7%) in NE contracted rings, but not in KCl contracted rings. The responses to D600 and DHA in KCl-contracted vessels were 79 +/- 2% to 104 +/- 3% and 5 +/- 1% to 21 +/- 3%, respectively. In another set of experiments, the effects of omega-3 fatty acids in the presence of albumin were examined; no significant differences in the induced relaxant responses were noted. These results suggest that the mechanisms of vascular relaxation, such as cyclic nucleotide elevation and calcium antagonism of potential-operated channels, are different from those induced by the omega-3 fatty acids. PMID- 1292582 TI - Effect of simvastatin on high density lipoprotein subfractions and apolipoproteins in type IIa hypercholesterolemia. AB - Changes in plasma concentrations of high density lipoproteins (HDL) and triglycerides may partly explain the ability of cholesterol-lowering drugs to decrease the incidence of coronary heart disease. We measured the response of fasting plasma lipids, lipoproteins, and apolipoproteins in 46 subjects with Type IIa hypercholesterolemia treated with simvastatin for 3 months. The initial dose of simvastatin (10 mg/day) was subsequently increased up to 40 mg/day if the plasma cholesterol concentration had not fallen below 5.2 mmol/l. Plasma concentrations of HDL cholesterol and of the apolipoproteins AI and AII were increased by simvastatin. The increase in HDL cholesterol (9%) was due to increases in both subfractions (HDL2 17%; HDL3 7%), changes that would be consistent with a beneficial effect on cardiovascular risk. Simvastatin decreased plasma triglyceride concentrations by 25%. Plasma total cholesterol concentrations fell by 35% after 3 months of treatment; this fall was proportional to the initial concentration and was due almost entirely to a 45% fall in low density lipoprotein cholesterol. In contrast, plasma concentrations of lipoprotein Lp(a) were not affected by simvastatin. PMID- 1292581 TI - Effects of sodium nitroprusside (MR7S1) and nitroglycerin on the systemic, renal, cerebral, and coronary circulation of dogs anesthetized with enflurane. AB - In beagle dogs anesthetized with enflurane-nitrous oxide, effects of sodium nitroprusside (SNP; MR7S1) and nitroglycerin (NTG) on hemodynamics and main organ circulation were studied to evaluate their effectiveness and safety as hypotensive agents during anesthesia. SNP (MR7S1) infusion (1-10 micrograms/kg/min) decreased arterial blood pressure in a dose-dependent manner. The hypotension was stable during the infusion. After discontinuation of infusion, the blood pressure rapidly returned to the initial level. The hypotension was associated with decreases in cardiac output and total peripheral resistance. NTG infusion (3-10 micrograms/kg/min) decreased arterial blood pressure, too, but the hypotension was less marked and not dose dependent, and the recovery was slower. Neither drug changed the heart rate. Infusion of SNP (MR7S1) and NTG did not change the hypotension induced by the injection of adenosine, SNP, and NTG. Furthermore, cerebral blood flow, cerebral oxygen consumption, and renal blood flow were unchanged during the hypotension produced by either drug. Coronary blood flow was decreased, but this was due to decreases in cardiac oxygen consumption. In conclusion, SNP (MR7S1) is superior to NTG as a hypotensive agent during anesthesia in efficacy, clear dose dependency, and rapid recovery. The hypotension induced by NTG as well as SNP (MR7S1) seems to have no undesirable effects on the circulation of important organs. PMID- 1292583 TI - The effect of transdermal nitroglycerin on exercise tolerance in relation to patch application time--a meta-analysis. AB - Disagreeing results have been reported in the many studies on continuous treatment with nitroglycerin patches. The effects on exercise tolerance are partly studied at the end of a 24-hour application period, and partly examined only a few hours after patch renewal. The present meta-analysis estimates the overall efficacy of nitroglycerin patches in trials with and without concomitant antianginal therapy, and investigates if the treatment effect depends on the patch application time. A computed search (MEDLINE) identified 110 publications, of which 17 trials on nitrate patch monotherapy and six trials on combined therapy satisfied the inclusion criteria. Data on "exercise duration" and "ST segment depression" were converted to a standardized treatment effect size d, and pooled to an overall treatment effect size d+. In tests 2-5 hours after patch renewal, moderate but significant effects of nitrate monotherapy were observed; d+ was 1.20 with regard to "ST-segment depression" and 0.39 with regard to "exercise duration" (both p < 0.0001). In contrast, 24 hours after patch application, the values for d+ were 0.09 (not significant) and 0.36 (p < 0.01), respectively. When adding the results from the six trials on combined therapy, d+ with regard to "exercise duration" was reduced to 0.28 (p < 0.0001) 2-5 hours after renewal and to 0.17 (p = 0.04) after 24 hours. Thus, the efficacy of continuous nitroglycerin patch treatment is moderate but evident during exercise tests 2-5 hours after patch renewal; however, it is reduced after 24 hours of patch application. PMID- 1292584 TI - Successful treatment of postoperative external biliary fistula by selective nasobiliary drainage. AB - A 25-year old man presented with a high output external biliary fistula after an operation for a giant hydatid cyst of the liver. Endoscopic sphincterotomy was inadequate to close the fistula. A nasobiliary tube was selectively inserted into the leaking hepatic duct and bile was continuously aspirated. The fistula and the residual cavity healed completely. Details of the patients' management using this alternative technique, are discussed. PMID- 1292585 TI - Multiple biliary papillomatosis. AB - Diffuse biliary papillomatosis is a rare bile duct tumour. We report a case of multiple biliary papillomatosis treated surgically with a transhepatic stent. Diffuse biliary papillomatosis involving intra and extrahepatic bile ducts is extremely rare. It is regarded as having low grade malignant potential. In this report a case of diffuse biliary papillomatosis with obstructive jaundice is presented. PMID- 1292586 TI - Giant pancreatic pseudocysts: procedures in management. PMID- 1292587 TI - Effect of intraoperative hypotension on survival after resection of colorectal liver metastases. PMID- 1292589 TI - Effect of alcohol consumption on variceal rebleeding and mortality. PMID- 1292588 TI - Should neither sclerotherapy nor propranolol be used prophylactically for oesophageal varices? PMID- 1292590 TI - Acute calculous cholecystitis. What is new in diagnosis and therapy? AB - The management of patients with acute calculous cholecystitis has changed during recent years. The etiology of acute cholecystitis is still not fully understood. Infection of bile is relatively unimportant since bile and gallbladder wall cultures are sterile in many patients with acute cholecystitis. Ultrasonography is first choice for diagnosis of acute cholecystitis and cholescintigraphy is second best. Percutaneous puncture of the gallbladder that can be used for therapeutic drainage has also diagnostic qualities. Early cholecystectomy under antibiotic prophylaxis is the treatment of choice, and has been shown to be superior to delayed surgery in several prospective trials. Mortality can be as low as 0.5% in patients younger than 70-80 years of age, but a high mortality has been reported in octogenerians. Selective intraoperative cholangiography is now generally accepted and no advantage of routine cholangiography was shown in clinical trials. Percutaneous cholecystostomy can be successfully performed under ultrasound guidance and has a place in the treatment of severely ill patients with acute cholecystitis. Laparoscopic cholecystectomy can be done safely in patients with acute cholecystitis, but extensive experience with this technique is necessary. Endoscopic retrograde drainage of the gallbladder by introduction of a catheter in the cystic duct is feasible but data are still scarce. PMID- 1292591 TI - Experimental and clinical evaluation of capsular and parenchymal total liver perfusion. Liver microcirculation. AB - Liver blood flow measurements obtained from both the liver surface and deep within the parenchyma, were correlated in an effort to assess the usefulness of laser-Doppler flowmetry for non-invasive monitoring of total liver blood flow, the probe being positioned on either the surface or within the liver parenchyma. In 23 Wistar rats and 10 biliary surgery patients, anaesthetized prior to gallbladder removal, liver microcirculation was measured at 4 points on the capsular surface, and consequently at 4 points deep within the parenchyma, using probes connected to a laser-Doppler flowmeter. The findings revealed that laser Doppler measurements on the liver surface and within the parenchyma were well correlated, as no statistically significant differences were found either in rats or humans. It is concluded that laser-Doppler flowmetry for monitoring of total liver perfusion can be applied either on the capsular surface or within the hepatic parenchyma. PMID- 1292592 TI - Fostering research growth in a nursing department. AB - Introducing research objectives in nursing departments is presenting challenges for nurse administrators. Where does one begin? The Nursing Department at Toronto General Hospital implemented a number of strategies to make the vision, "research integrated with daily practice", a reality. The strategies served to translate the vision into concrete actions. Three broad themes are used to describe the strategies--bringing resources together, raising awareness about research and conducting research projects. This article describes some of the strategies we implemented in anticipation that other Nursing Departments may benefit from our experiences. PMID- 1292593 TI - Development of a research committee at a community hospital. AB - This paper describes the process undertaken in setting up a nursing research committee in a community hospital in British Columbia. The primary goal of the committee is to increase awareness among bedside nurses of the value of research in their practice. This goal is based on the belief that research conducted by practicing nurses validates existing practice and promotes quality patient care, important concerns for nurse administrators. PMID- 1292594 TI - Five years in the life of a nursing research and professional development division. AB - The Nursing Research and Professional Development Directorate was established to support the growth of research of professional practice in the Nursing Department. Designed as an innovative work structure, it elicited high commitment from its members, contributed to their satisfaction and freed their creative potential. The organizational structure and processes were designed to satisfy the important work criteria of involvement in decision-making, equity, dignity, security, job challenge, autonomy, mutual trust and open communication. The Directorate not only brought together expertise in research and professional development but also created mechanisms to ensure the expertise was available at the bedside. With a mandate of developing and transmitting knowledge, the availability of that knowledge in the practice arena is a mark of our success. This article describes our formative experiences including the structure, processes and outcomes of our work. The challenges we faced are also discussed. PMID- 1292595 TI - Focus on the future. PMID- 1292596 TI - Job sharing: impact on the general well-being of female nurses. AB - Women today have more life choices than ever before: career, marriage, motherhood, or any combination of the three. Unfortunately little has been done to make up for the competing demands of these roles. Job sharing may be the alternative choice which allows working women to cope with the multiple stressors of having it all--career and family without having to sacrifice their sense of well-being. Nursing administrators stand to benefit from a work schedule alternative which promotes a healthy balance between work and family. Job sharing may offer a solution to the loss of valued staff nurses who require less than full-time employment. In order to compare the general well-being of female nurses who are employed in full-time, casual part-time, and job sharing positions a descriptive correlation study was conducted. One hundred female nurses between the ages of 22 and 40 who have their children living at home with them completed the 18-Item General Well-Being Questionnaire. Additional questions regarding job satisfaction, physical health status, and demographic data were also included. The results of the analyses of variances revealed there were no statistical differences between the general well-being scores of women working full-time, casual part-time, or job sharing. However, crosstabulations showed the job sharing nurses had the highest ratings for job satisfaction and physical health status. PMID- 1292597 TI - [Current problems in syphilis]. PMID- 1292598 TI - [Tuberculous meningitis in patients without HIV infection. Presentation of 21 cases]. AB - BACKGROUND: Tuberculous meningitis accounts for 5% to 12% of all extrapulmonary tuberculosis cases in western-hemisphere population non infected by HIV virus, and carries a high mortality rate. METHODS: We analyze retrospectively 21 patients with tuberculous meningitis in HIV negative patients seen from 1975 to 1989, with emphasis on clinical, laboratory and therapeutic features. RESULTS: In 48% of cases there were not typical meningeal signs, and 61% of patients showed neurological focal signs and/or seizures. CSF examination revealed a clear fluid with high cell counts (mostly lymphocytes), high protein and low sugar levels in 67% of cases. However, the microbiologic examination had a low yield of diagnosis (33%). The clinical course is prolonged, and treatment is usually delayed. Morbidity and mortality were high (34% and 10% of cases). In this study, the use of steroids did not show a significant reduction in mortality nor in neurological sequelae. CONCLUSION: Tuberculous meningitis in HIV negative patients is a chronic infection, without meningeal signs in most cases and linked to a high rate of neurological defects. The microbiologic tests have low yield of diagnosis. Steroid drugs seem to be indicated only if there are additional complications. PMID- 1292599 TI - [Septic shock: epidemiology and prognosis]. AB - As part of an infection control program in ICU, we studied prospectively 1500 consecutive patients admitted to a medical and surgical ICU from January 1988 to July 1990. Over this period of time, 69 patients developed septic shock, and 38 of them died (55.1%). Primary source of infection was the lower respiratory tract or intraabdominal in more than 50% of cases, and were related to a high mortality rate, however SS arising from a biliary tract infection is associated with a mortality rate below 20%. In the univariate analysis, nosocomial origin (p = 0.0001), creatinine serum level > 175 mumol/l (p = 0.005), multiple organ failure in the first 24 hours after shock started (p = 0.02), underlying cancer disease (p = 0.02) or liver cirrhosis (p = 0.03) were associated with a statistically significant higher risk for dying. No differences were found regarding age, sex, admission date, coma, recent surgery, prior cardiac arrest, diabetes, organ transplantation, corticosteroid therapy, cancer chemotherapy, absence of fever, bacteriology of the infection and appropriate antibiotic therapy. The multivariate analysis further identified that creatinine serum level > 175 mumol/l (p = 0.004), underlying cancer disease (p = 0.005), liver cirrhosis (p = 0.02) and nosocomial-acquired infection (p = 0.02) were independently associated to a higher risk for dying. These data allows the identification of factors related to a worst outcome. The high mortality rates recorded for septic shock still recommends the rapid transfer of the patient to an ICU as well as the use of aggressive therapy in all cases. PMID- 1292600 TI - [Molecular study of ampicillin resistance in clinical isolates of Salmonella]. AB - BACKGROUND: The purpose of this work was to study the molecular basis of beta lactamase production in ampicillin-resistant strains of Salmonella spp. METHODS: It was performed analytical isoelectric focusing of beta-lactamases produced by a group of 33 strains selected in basis of their resistance phenotype. Plasmid profile analysis and assays of transferable drug resistance were developed. The study was completed by hybridization experiments with an intragenic TEM probe which allowed the location of the bla-TEM gene. RESULTS: By analytical isoelectrofocusing we found that 26 out of the 27 ampicillin-resistant strains produced beta-lactamases with pl 5.4 and/or 5.6 corresponding to TEM-1 and/or TEM 2 type. Analysis of plasmid DNA revealed in almost all strains plasmids ranging in size from 1.1 to 125 Mdal. This plasmids were responsible of the resistance and, moreover, were able to transfer the resistance by conjugation mechanisms. Southern blot analysis detected the gene that code the TEM beta-lactamase at the 125, 8 and 5.8 Mdal plasmids. CONCLUSIONS: Resistance to ampicillin in the strains of Salmonella studied was due to the presence of TEM type beta-lactamases coded by conjugative plasmids. These plasmids coded also resistance to other antimicrobial agents. Our results showed that the use of a DNA probe to the detect TEM-type beta-lactamases using a non radioactive probe, could be a suitable alternative to isoelectric focusing. PMID- 1292601 TI - [Prevalence and treatment of bacteriuria in the geriatric population]. AB - The aim of this study was to evaluate the prevalence of asymptomatic bacteriuria and its prognostic factors in a geriatric population living in a nursing home. Seventy-eight patients (68 females, 10 males) with a mean age of 82 +/- 6 years (range: 60-94) were studied. Once symptomatic infection is ruled out and the risk factors had been analyzed, a urine culture was performed in all cases. We then identified two different population groups: asymptomatic bacteriuria without risk factors (group A), and asymptomatic bacteriuria with risk factors (group B). Overall prevalence of asymptomatic bacteriuria was 38.5% (Group A: 23%, group B: 63%; p < 0.001). Considering all patients with bacteriuria, 50% of cases (15 out of 30 patients) had urine incontinence, 40% suffer from severe limitation of movements and 70% had a past history of pregnancy. The same figures for the population with negative urine culture were 12.5%, 14.5%, and 46% respectively (p < 0.01). In group B, 79% of cases had more than one RF, including all patients with the association of urine incontinence, movement limitation and diabetes. In group A, 93% of asymptomatic bacteriuria were due to E. coli with low adhesin expression (27%) whereas in group B, E. coli was isolated in 44% asymptomatic bacteriuria cases, with high adhesin expression (71.5%), other enteric gram negative bacilli (31%), non-fermentative gram-negative bacilli (19%) and gram positive cocci (6%). Group A patients were treated with a single dose of ciprofloxacin (500 mg) with elimination of bacteria in urine in 91% of cases (at one week) and 73% of cases (at one month).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292602 TI - [Pulmonary cryptococcosis in AIDS]. AB - We present here three AIDS patients with disseminated cryptococcal infection and lung involvement. Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding. Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case. One patient has also simultaneous infection by P. carinii. Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non induced sputum exam in two cases. All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole. Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates. The presence of C. neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable. PMID- 1292603 TI - [Mycobacteriosis during 1980-1990 in a Madrid hospital]. AB - BACKGROUND: To assess the incidence and features of environmental mycobacteria that can produce disease over a ten years period (1980-1990) in an University Hospital from Madrid (Spain). METHODS: Medical records of all patients in whom and environmental mycobacteria that can produce disease had been isolated were reviewed and classified as definite, possible or not clinically significant isolates, according to clinical features and microbiologic findings. RESULTS: Mycobacterium species were isolated in 415 patients (491 clinical samples over a total of 3003, 16.3%). In 29 patients a environmental mycobacteria that can produce disease was identified. Medical records from 25 patients were retrieved, being this mycobacteria isolated classified as with definite clinical significance in 8 cases, with possible clinical significance in 4, and without clinical significance in 13 cases. Clinical features in the significant cases were: lung infection (3 cases), pleural and pericardial disease (1 case), peritonitis (1) and soft tissue infection (1) Two patients died. Surgical excision of the lesion was performed in the remaining patients, and clinical cure was achieved in five cases. CONCLUSIONS: The most prevalent mycobacterial infection in our environment is still due to M. tuberculosis infection, followed by M.avium-intracellulare. Surgical treatment is a valid approach in patients with localized infection by environmental mycobacteria that can produce diseases. PMID- 1292604 TI - [Hepatitis E virus]. PMID- 1292605 TI - [Eosinophilia in a patient from Cape Verde]. PMID- 1292606 TI - [Hematuria in a traveling doctor]. PMID- 1292607 TI - [Tracheostomy wound infection caused by Stomatococcus mucilaginosus]. PMID- 1292608 TI - [Sepsis caused by Staphylococcus lugdunensis]. PMID- 1292609 TI - [Empyema caused by Salmonella in a patient with alcoholism]. PMID- 1292610 TI - [Maxillary sinusitis caused by Alternaria sp. in a bone marrow transplantation patient]. PMID- 1292611 TI - [Coinfection by Nocardia asteroides and Mycobacterium avium- intracellulare in a patient with AIDS]. PMID- 1292612 TI - Surfactin/iturin A interactions may explain the synergistic effect of surfactin on the biological properties of iturin A. AB - Iturin A and surfactin are two lipopeptides extracted from a same strain of Bacillus subtilis. Iturin A possesses antibiotic and antifungal activities and surfactin is a strong surfactant. The presence of surfactin, at a concentration at which, alone, it is inactive, increases to a very large extent the haemolysis percent induced by iturin A. This synergistic effect seems to be in relation with interactions between iturin A and surfactin. Iturin A adsorbs to and penetrates into surfactin monolayers. Iturin A and surfactin are miscible and interact specifically in mixed monolayers. PMID- 1292613 TI - Expression of the full-length rabbit prolactin receptor and its specific domains in baculovirus infected insect cells. AB - The prolactin receptor is a membrane protein mainly involved in the development of the mammary gland and in lactation in mammals. We used specific cDNA constructs and the insect/baculovirus expression system and produced independently and in large amounts several recombinant forms of the rabbit mammary gland prolactin receptor: the full-length receptor (L1, L2), a truncated membrane form (S), a secretable form of the extracellular domain (E) and two forms of the intracellular domain (I1, I2). Of these forms, the L1 and L2 are associated with the membrane fraction, the E is predominantly secreted into the medium and the I1 and I2 are expressed as soluble proteins and surprisingly, a great portion accumulates in the culture medium. The molecular mass (94 kDa) of the expressed full-length receptor corresponds to the translation product of the entire cDNA coding region. The receptor biochemically identified in the rabbit mammary gland is however much shorter. Thus, in the mammary gland, the receptor presumably undergoes post-translational modifications. The receptor forms L1, L2 and S bind prolactin with specificity and affinity similar to those reported for the native receptor. They also interact with two monoclonal antibodies, M110 and A917, specific for the native conformation of the hormone-binding site. The I1 and I2 forms do not bind prolactin, whereas the E form does. Thus, the hormone binding site is located in the extracellular domain which can function autonomously as a PRL-binding soluble protein. However, the E form binds prolactin with a higher affinity than the native receptor and it does not bind one of the two antireceptor monoclonal antibodies, known to be hormone binding site specific. Thus, the conformation of the native receptor and that of the E form differ. PMID- 1292614 TI - Organization of repetitive DNA sequences in the genome of the echinoderm Holothuria tubulosa. AB - The abundance of repetitive DNA in the haploid sea cucumber genome has been determined by screening a Holothuria genomic DNA library for clones containing repeated sequences using reverse genome hybridization. Analysis by in situ plaque hybridization of a set of 1132 clones has revealed the presence of repetitive DNA sequences in about 38.1% of the clones screened. The distribution of the reiterated DNA has been further analyzed by restriction endonuclease digestion of seven randomly selected repetitive clones. The repeated sequences have a fairly uniform distribution of lengths with an average length value of 7.3 kb. Analysis of the measurements suggests that the repetitive sequences are interspersed among longer single copy sequences with an average spacing interval of about 47.3 kb indicating that the repetitive and single copy DNA in the Holothuria genome are arranged in a long-period interspersion pattern. PMID- 1292615 TI - Detection of satellite DNA in Palorus ratzeburgii: analysis of curvature profiles and comparison with Tenebrio molitor satellite DNA. AB - Very abundant and homogenous satellite DNA has been found in the flour beetle Palorus ratzeburgii, representing 40% of its genome. Sequencing of 14 randomly cloned satellite monomers revealed a conserved monomer length of 142 bp and an average A+T content of 68%. Sequence variation analysis showed that base substitutions, appearing with a frequency of 2.3%, are predominant differences among satellite monomers. The satellite sequence is unique without significant direct repeats and with only two potentially stable inverted repeats. After electrophoresis of satellite monomers on native polyacrylamide gel retarded mobilities characteristic for curved DNA molecules are observed. The curvature profiles and DNA helix axis trajectory are calculated on the basis of three different algorithms. These calculations predict that P ratzeburgii satellite DNA forms a left-handed solenoid superstructure. Comparison of described features with other satellite DNAs reveals some striking similarities with satellite DNA from related species Tenebrio molitor, which belongs to the same family of Tenebrionidae. Both satellites are very abundant and homogenous with the same, highly conserved monomer length, although there is no homology at the nucleotide level. Their monomers, as well as multimers, exhibit very similar retarded electrophoretic mobilities. The calculated curvature profiles predict two bend centers in monomers of each satellite, resulting in a model of left-handed solenoid superstructures of similar appearance. PMID- 1292616 TI - Refined conditions for selective modifications of rabbit skeletal myosin light chains. AB - We selectively modified the LC1 and LC2 N-terminus as an approach to understand the function of skeletal myosin light chains and their possible implication in some diseases. Three new myosin isoforms were thus created, namely: myosin [(P)LC1'], myosin-[(T)LC2'] and myosin-[(CT)LC2"] in which the N-terminus was selectively cleaved at Lys7 in (P)LC1', Arg8 in (T)LC2' and Phe19 in (CT)LC2". In order to obtain species with a minimum amount of secondary cleavages, eight to 12 different conditions were screened for each species and the two most efficient conditions were tested at the preparative scale. PMID- 1292617 TI - Purification of a heparin binding FGF receptor (HB-FGFR) from adult bovine brain membranes. AB - A new form of high affinity fibroblast growth factor receptor has been purified from adult bovine brain membranes. Purification was performed by chromatography on DEAE-Trisacryl and wheat germ agglutinin-agarose followed by FGF-2 affinity chromatography. Affinity labeling of purified fractions with 125I-FGF-2 showed after cross-linking a 170-kDa complex, suggesting the existence of a 150-kDa FGF receptor. No cross-reactivity with anti-FGF receptor 1 (FGFR-1 or flg) or with anti-receptor 2 (FGFR-2 or bek) antibodies could be detected with this partially purified receptor. Heparitinase treatment of the partially purified FGF receptor abolished the formation of the ligand receptor complex. The complex was restored in the presence of heparin in a dose dependent fashion, supporting the idea that heparin-like molecules are needed for proper binding. Further purification of the receptor was achieved by heparin-Sepharose affinity chromatography and yielded a purification of over 320,000-fold. The purified receptor fraction was radiolabeled and loaded on RPLC C4 column. Eluted fractions were analysed by SDS PAGE. A major 150-kDa band was detected. These data show for the first time a new form of FGF receptor isolated from bovine brain membranes. This purified receptor displays affinity for heparin and was therefore named heparin binding FGF receptor (HB-FGFR). It remains unclear whether the receptor is a proteo-heparin sulfate or whether heparans are strongly associated and therefore are copurified. Large scale preparations are in progress for core protein structure studies. PMID- 1292618 TI - Differential expression of PDGF A- and B-chain genes and production of AA and AB dimers by activated human blood monocytes. AB - Platelet-derived growth factor (PDGF) is composed of two chains (A and B) bound by disulfide bridges. Blood monocytes (BM) express the c-sis proto-oncogene, the gene coding for PDGF B-chain, and release PDGF. To evaluate PDGF release and A- and B-chain gene expression by BM, normal BM were cultured with LPS and specific transcripts for PDGF A- and B-chain genes were detected by Northern analysis and PDGF dimers by specific Elisas. Normal BM did not spontaneously express either A- or B-chain gene while, when activated, PDGF B-chain expression was precocious (maximum at 1 h) and decreased over 24 h; PDGF A-chain transcripts were present after 4 h and progressively increased over 24 h. Furthermore, activated BM released more AB dimers than AA dimers and almost no BB dimers. This observation confirms the concept of PDGF A- and B-chain separate gene regulation, and defines the specific molecular pattern of PDGF released by activated BM. PMID- 1292619 TI - 20-alpha-Hydroxysteroid dehydrogenase from pseudopregnant rat ovary: obtention and characterization of a monoclonal antibody against the enzyme activity. AB - The enzyme 20-alpha-hydroxysteroid dehydrogenase (20-alpha-HSD) was purified from pseudopregnant rat ovaries and used as antigen for the development of a monoclonal antibody by the hybridoma technique. Spleen cells of BALB/c mice immunized with purified 20-alpha-HSD were fused with SP2/0 mouse myeloma cells. Among the colonies of hybrid cells, one (designated mAb-HSD 11) was found to be secreting antibodies (IgM) able to inhibit 20-alpha-HSD activity. The antibody secreting hybridome was amplified by ascitic fluid production and the monoclonal antibody purified by Bakerbond ABx procedure. Purified mAb-HSD 11 was able to inhibit 20-alpha-HSD activity in a dose-dependent manner. Studies of Michaelis constants of 20-alpha-HSD indicate that this monoclonal antibody increases the Km for 20-alpha-dihydroprogesterone and decreases the Vmax. PMID- 1292620 TI - [Changes in the epidemiological profile of dentofacial anomalies and in the status of orthodontic treatment between 1979 and 1989 in the city and district of Leipzig (an ICS-I replication study). International Study of Dental Manpower System]. AB - Ten years after the Leipzig ICS-I-Study a replication study was performed in analogous fashion and in the same territory. Using the COCSTOC methods changes in the prevalence of dental-facial anomalies and the orthodontic state of treatment were determined in a random sample of 13-14-year-old school children. The prevalence of anomalies had decreased within a decade from 43% to 35%. At the same time the percentage of children not under treatment decreased from 14% to 10%. The causes are seen mainly in the area under consideration and the related preservation of the support zone until the physiological replacement of teeth as well as a reduced extraction rate for primary and permanent teeth. PMID- 1292621 TI - [The follow-up of the orthodontic treatment of facial cleft patients with the Gottingen computer-supported documentation system]. AB - The care of patients with cleft lip, alveolus, and palate demands supervision of the development and progress over a long period of time. It also requires a standardized and systematic basic documentation. In our cleft center the documentation is summarized on one sheet of paper with DIN-A4 formation (297 x 210 mm). The use of electronic data processing improves the documentation. The storage of general and medical data has been supplemented by a personal computer system, PC-System. Five years after developing of this computer aided documentation system several patients are shown as examples for the application of this system for longterm control patients with cleft lip, alveolus, and palate. PMID- 1292622 TI - [Mandibular condyle fractures in childhood--the clinico-roentgenological follow up]. AB - In a clinical and roentgenographical follow-up study in 35 children, who had suffered a fracture of the condylar process of the lower jaw, the following observations were made on the average 61 months after conservative treatment: The clinical outcome ranged from "satisfactory function" to "restitutio ad integrum". Best results were achieved after unilateral displaced fractures, while only few children showed a "restitutio ad integrum" after bilateral fractures or/and after fracture dislocations. In children, who were less than 8 years old, the results were much better than in older ones. Roentgenographically the morphological regeneration after fracture dislocations was frequently incomplete--in the contrary to fractures with displacement. PMID- 1292623 TI - [Changes in the condyle path following fractures with dislocation of the maxilla]. AB - In spite of rigid internal fixation with miniplates after midfacial fractures, dislocation of the previously mobilized fragment in the dorsal direction is conceivable. Thus, the mandible would be forced into a dorsal position over the occlusion. As a result, changes of the condyle paths, such as limitations or deviations from the normal, would be possible. Six patients, who had sustained midfacial fractures with mobilization or dislocation of the maxilla, were followed up. The condyle paths were recorded at the earliest time possible after rigid internal fixation and after removal of the miniplates. We used the electronic computer-assisted registration system (ECRS), which allows three dimensional registration without occlusal interferences. The patterns of the TMJ movements were not impaired, arguing against the dorsal transposition of the maxilla. The extent of the movements during the first postoperative weeks, however, was significantly reduced in some cases, even if intermaxillary fixation was not carried out. In our opinion, this is due to the periarticular infiltration and a varying elasticity of the articular capsule in different directions. PMID- 1292624 TI - [The bacteriological and clinical aspects of odontogenic soft-tissue infections]. AB - The antibiotic treatment is proved to be an effective supplement for the surgical therapy of odontogenic soft-tissue infections. For the use of antibiotics the knowledge of the oral bacterial flora and its state of resistance is very essential. In a catamnestic study the clinical records of 250 patients with orofacial infections, who were under stationary treatment in the Dept. of Maxillofacial Surgery, University Clinic Gottingen, were analyzed. The results show, that the bacterial flora has not changed basically during the last decade. Predominantly mixed aerobic and anaerobic infections can be found. Increasing importance must be attached to penicillin-resistant Staphylococci and anaerobic pathogens. Penicillins must be further considered as antibiotics of the first choice. For an extension of the antimicrobial activity the combination with a betalactamase inhibitor is useful. PMID- 1292625 TI - [Necrotizing sialometaplasia]. AB - The necrotising sialometaplasia is a rare disease of the orofacial system. The minor salivary glands of the palate are the main localisation. It's clinical importance consists in the possibility of confusion with squamous cell carcinoma or the mucoepidermoid tumor. The authors report on 3 cases and discuss the etiology and the diagnostic of this disease. PMID- 1292626 TI - [The limits of root planing in the furcation area. A mathematical comparison of the radii of curvature on the root surfaces and on the curettes]. AB - In order to draw some conclusions about the furcation region accessibility for periodontal instruments and their cleaning effect, the curvature radii of the root faces of 31 lower molars were mathematically determined and compared with the curvature radii of the working end of normally available curettes. From the results of this work it can be seen, that the Gracey curettes have an essential greater curvature radius as the curvature radius of the root faces. On the other site the special curettes for root planing in the furcation region have a smaller curvature radius as that of the root faces. Using the instruments included in this study, it is not possible to achieve an optimal root planing. PMID- 1292627 TI - Cloning, expression and characterization of ovine interleukins 1 alpha and beta. AB - Ovine interleukin 1 alpha (IL-1 alpha) c-DNA, obtained by polymerase chain reaction, has been cloned into pTZ18R and pTZ19R. The resulting DNA sequence shows close homology with the bovine sequence. The derived amino-acid sequence shows conserved motifs similar to those observed in all species studied so far. No signal peptide is seen. Northern blots of RNA from lipopolysaccharide (LPS) stimulated ovine alveolar macrophages show IL-1 beta m-RNA to be produced earlier than and to be more transient than IL-1 alpha m-RNA. c-DNAs coding for the IL-1 alpha proprotein and IL-1 alpha and IL-1 beta mature proteins have been cloned and expressed in the yeast Ty-VLP system as fusion proteins. The resultant IL-1 protein preparations, cleaved from their fusion partners by the action of activated coagulation Factor Xa, are 80-95% pure and show biological activity in standard thymocyte co-mitogen and cartilage degradation assays for IL-1. Some species specificity is observed in that sheep thymocytes are more responsive to ovine rIL-1 than are mouse thymocytes. The presence of a Factor Xa cleavage site in the IL-1 alpha proprotein suggests that Factor Xa may be involved in the processing of ovine IL-1 alpha to its mature form. PMID- 1292628 TI - Gene transfer investigations of p56-LCK function in IL-2-dependent T-cell lines: implications for mechanisms of IL-2-signal transduction. AB - Recently, the SRC-like non-receptor protein tyrosine kinase p56-LCK has been shown to physically associate with the interleukin-2 receptor (IL-2-R) complex and to undergo rapid elevations in its tyrosine kinase activity upon stimulation of T lymphocytes with IL-2. The functional significance of p56-LCK kinase activation for IL-2-mediated lymphocyte responses, however, has never been directly assessed. Using gene transfer approaches, we have achieved markedly elevated levels of p56-LCK kinase activity in the IL-2-dependent cytolytic T-cell line CTLL-2 and the helper line HT-2. CTLL-2 and HT-2 cells that were stably transfected with expression plasmids encoding either the normal human p56-LCK or a constitutively active version of the mouse p56-LCK kinase (LCK[Y505]) contained striking elevations in the levels of tyrosine phosphorylation on several proteins (34-36, 50-60, 62-68, 77-78, 104-110 kDa), as determined by immunoblot analysis using anti-phosphotyrosine antibodies. CTLL-2 and HT-2 LCK- and LCK(Y505F) transfected cells remained dependent on IL-2 for their growth and survival in culture despite the findings that (i) IL-2 specifically stimulated elevations in the activity of the endogenous p56-LCK in untransfected CTLL-2 cells without affecting the activities of the other SRC-like kinases in these cells (p59-FYN, p62-YES) and that (ii) IL-2-mediated regulation of p56-LCK correlated with IL-2 driven proliferation of these T cells. Specifically, no elevation in the proliferation (DNA synthesis) or growth of these T cells was found at any of the concentrations of IL-2 examined (0.01-25 U/ml), relative to untransfected and control transfected cells. Furthermore, when cultured in the absence of IL-2, transfected T cells whose relative levels of p56-LCK activity were elevated by approximately 20-50-fold died with the same kinetics as control cells and underwent apoptosis, as defined by uptake of trypan blue dye and DNA fragmentation assays, respectively. Taken together, these data indicate that while IL-2 can up-regulate the enzymatic activity of p56-LCK, elevated levels of p56-LCK tyrosine kinase activity are insufficient to stimulate IL-2-mediated pathways required for T-cell growth and survival. These findings thus imply the existence of other signal-transducing molecules, besides p56-LCK, that physically participate in IL-2R complexes and that are necessary for initiation of the biochemical events ultimately responsible for IL-2's pleiotropic actions on lymphocytes. PMID- 1292629 TI - Human B cell lines express the interferon gamma gene. AB - Interferon gamma (IFN-gamma) production has been attributed exclusively to activated T cells and NK cells. We sought to determine whether human B cells express IFN-gamma. We studied 28 B cell lines including Epstein-Barr virus (EBV)+ normal lymphoblastoid B cell lines (N = 7), EBV+ B cell lines derived from patients with Burkitt's lymphoma with (N = 6) or without AIDS (N = 8), as well as seven EBV- B cell lines. All cell lines were studied by reverse transcription polymerase chain reaction (RT-PCR). We detected constitutive expression of IFN gamma in every B cell line. The tumor promoters PMA and teleocidin appeared to enhance this IFN-gamma expression in nearly every B cell line. The 517 bp amplicons spanning the entire protein coding region of the IFN-gamma mRNA from three representative lines were sequenced, definitively establishing that B cell IFN-gamma is identical to IFN-gamma from activated T cells and is not altered by derivation of the B cell lines from AIDS patients or by EBV status. Detection of IFN-gamma in the entire panel of EBV+ and EBV- cell lines suggests that the IFN gamma gene is broadly expressed by human B cells. Our data imply that human B cells can be activated to produce IFN-gamma, further enmeshing B cells in the dynamics of immunoregulation. PMID- 1292630 TI - Multiple cytokine secretion by IL-7-stimulated human T cells. AB - The induction of cytokine secretion by human peripheral blood (PB) T cells was examined. Highly purified T cells stimulated with interleukin 7 (IL-7), in the absence of co-mitogen, secreted IL-2, IL-4, IL-6 and interferon gamma (IFN-gamma) upon restimulation with phorbol ester and ionomycin. In contrast, induction of T cell cultures initiated with IL-2 or IL-4 yielded only low levels of IL-6 and virtually undetectable levels of IL-4 or IFN-gamma, while IL-2 secretion was reduced. No difference was seen in the ability of CD4+ and CD8+ subpopulations, grown in IL-7, to produce cytokines. In contrast, subdivision of T cells into memory and naive populations using the CD45RO monoclonal antibody (mAb) UCHL1, revealed that almost all of the potential to secrete IL-4 and IL-6 in response to IL-7 resided in the CD45RO+ memory population. Stimulation of cytokine-secreting cells appeared to be a direct effect of IL-7 as neutralizing antibodies directed against IL-2 and IL-4 had no effect on the levels of cytokines produced. The differences observed in the ability of IL-2, IL-4, and IL-7 to potentiate cytokine production was supported by measurement of cytokine mRNA levels by PCR. The elevated levels of cytokine secretion seen in cells cultured with IL-7 was not due simply to increased viability in these cultures compared with those containing IL-2 or IL-4, as these populations showed comparable cloning frequencies in phytohemagglutinin (PHA) + IL-2. These results demonstrate that IL 7, in the absence of co-mitogen, is a potent initial stimulus for multiple cytokine production by human T cells upon restimulation. PMID- 1292631 TI - The in vitro growth of murine high proliferative potential-colony forming cells is not enhanced by growth in a low oxygen atmosphere. AB - The growth of primitive murine hematopoietic progenitors, high proliferative potential colony-forming cells (HPP-CFC), has been reported to be improved in low O2 tension cultures. In this report we investigated the growth of HPP-CFC stimulated by combinations of interleukin (IL)-1, IL-6, kit-ligand (KL), granulocyte (G) colony-stimulating factor (CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF) and IL-3 in clonal cultures incubated at 7% or 21% O2 tension. Neither the numbers of HPP-CFC colonies nor the number of cells per HPP-CFC colony differed significantly between cultures grown under 7% or 21% O2 tension. The mean number of cells per HPP-CFC colony was found to range from 3.9 x 10(4) to 2.2 x 10(5). The smallest HPP-CFC colonies were stimulated by the cytokine combination IL-1 + IL-6 + KL, whereas the largest colonies were stimulated by a combination of all seven cytokines tested. The growth of erythroid colonies from murine or human bone marrow did, however, show some enhancement when cultured at a lower O2 tension. These results demonstrate that the growth of murine HPP-CFC was not compromised when cultured at ambient O2 concentration. PMID- 1292632 TI - Activated human Langerhans cells express mRNA for IL-1 alpha and IL-1 beta and produce these cytokines but do not secrete them. AB - Human Langerhans cells (LC) were isolated from epidermal cell preparations by panning with mouse anti-CD1 monoclonal antibody. RNA was prepared and probed for the presence of mRNAs for various cytokines using radiolabeled cDNAs. After stimulation with phorbol myristate acetate LC express RNA for interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta) and produce proteins but do not secrete them at detectable levels. LC-associated IL-1, particularly IL-1 alpha, may play a role in antigen presentation. PMA did not induce IL-6 expression in LC. The addition of lipopolysaccharide, a muramyl dipeptide analog, ionomycin, IL 1 alpha, tumor necrosis factor-alpha, insulin-like growth factor-1 or IL-6 did not induce IL-1 mRNA in LC. UVB augmented IL-1 beta mRNA expression. Glucocorticoids did not detectably affect IL-1 alpha or IL-1 beta mRNA levels following PMA induction, however, staurosporin inhibited IL-1 beta mRNA synthesis. Thus the inducers and regulators of IL-1 formation in human LC and monocytes are not identical. PMID- 1292633 TI - Endotoxin and Staphylococcus aureus enterotoxin A induce different patterns of cytokines. AB - The effects of Staphylococcus aureus enterotoxin A (SEA) and lipopolysaccharide (LPS) in cytokine production were assessed at the single cell level in cells obtained from healthy blood donors. Cytokine production was studied with UV microscopy of fixed and permeabilized cells stained with cytokine specific monoclonal antibodies. The cytokines evaluated included tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-2, IL-4, interferon (IFN)-gamma and TNF-beta. LPS exhibited marked production of IL-1 alpha, IL-1 beta, TNF-alpha, IL-6 and IL-8. After LPS stimulation IL-1 alpha, IL 1 beta, TNF-alpha and IL-8 were the dominating products, all peaking at or before 4 hours after cell stimulation. In addition, IL-10 production was evident after 12 hours of cell stimulation. The T-lymphocyte-derived cytokines TNF-beta, IL-2, IFN-gamma and IL-4 were never detected in the cultures. All cytokine production, except IL-8, was downregulated at 96 hours. In contrast, peak production of IL-1 alpha, IL-1 beta and IL-8, which were the dominant products, occurred after 12 hours in the SEA-stimulated cultures. Further, a significant T-lymphocyte production of TNF-beta, TNF-alpha, IFN-gamma and IL-2 was found with peak production 12-48 hours after initiation. Only low amounts of IL-6 were evident. The two types of cytokine pattern and kinetics found may correspond to the different clinical conditions after invasive Gram-negative Escherichia coli vs Gram-positive Staphylococcus aureus infections in humans, with a much more rapid onset of disease after E. coli infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292634 TI - Induction of HLA class I mRNA by cytokines in human fibroblasts: comparison of TNF, IL-1 and IFN-beta. AB - Expression of HLA class I antigens is known to be regulated by various cytokines at both the mRNA and protein levels. We have examined the induction of HLA-B7 by tumor necrosis factor alpha (TNF), interleukin 1 alpha (IL-1) and interferon beta (IFN-beta) in normal human diploid FS-4 fibroblasts. Optimal induction of HLA-B7 by TNF at 24 h was shown to require a continuous presence of TNF. Since TNF also induces IFN-beta in these cells and the latter cytokine itself has the capacity to upregulate HLA class I expression, we investigated the role of autocrine IFN beta in the induction of HLA-B7 by TNF. Experiments with neutralizing polyclonal antibodies to recombinant IFN-beta showed that the induction of HLA-B7 mRNA by TNF was partially dependent on autocrine IFN-beta. However, TNF and IFN-beta induced HLA-B7 mRNA with similar kinetics and treatment with saturating concentrations of both TNF and IFN-beta resulted in an additive or possibly synergistic response. The latter findings support the idea that induction of HLA class I by TNF is not mediated solely by autocrine IFN-beta produced in response to TNF. In addition, experiments with the protein synthesis inhibitor cycloheximide suggested that the induction of mRNAs for both the heavy and light (beta 2-microglobulin) chains of the HLA class I antigen by TNF did not require de novo protein synthesis. IL-1 was also shown to increase steady-state mRNA levels of HLA-B7 with kinetics similar to those of TNF and IFN-beta in FS-4 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292635 TI - Identification of a monocyte-derived factor which regulates synthesis of insulin receptors on activated T-lymphocytes (MIRRF). AB - The regulation of the insulin receptor on the activated T-lymphocyte was studied. It has been previously shown that the monocyte with its constitutive insulin receptor can signal the quiescent T-lymphocyte with respect to ambient insulin concentration which regulates the copies of insulin receptors synthesized during the lymphocyte activation event. In this communication it is shown that the vehicle by which the monocyte signals the T-lymphocyte is a soluble, small molecular weight protein. Initially a bioassay was established to test the putative monocyte-derived factor in which freshly prepared purified populations of monocytes were incubated with insulin, extensively washed, and replated with lymphocytes in microwells or across a 3 microns filter from lymphocytes using the appearance of insulin receptors on T lymphocytes responding to lectin as measured by a radioligand binding assay as the outcome variable. Dose response and time course relationships were established to develop the ideal conditions for the bioassay. It was shown that the monocyte-derived insulin receptor regulatory factor (MIRRF) could be readily detected in conditioned medium of insulin incubated and then washed monocytes as a starting point for attempts at later purification. Using rats fed an essential fatty acid deficient diet (EFAD), incapable of generating standard prostanoids, it was demonstrated that the MIRRF was readily detectable in our standard bioassay revealing that the factor was not a member of the arachidonic acid family. Lastly, it was shown that MIRRF is cycloheximide sensitive and either is a protein or requires protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292636 TI - Cytokine responsiveness in germfree and conventional NMRI mice. AB - 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. PMID- 1292637 TI - IL-1 synergizes with ARA-C in aborting the development of chloroleukemia while protecting from ARA-C-induced alopecia in the rat model. AB - 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. PMID- 1292638 TI - Suppression of IL-2-induced SAA gene expression in mice by the administration of an IL-1 receptor antagonist. AB - 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. PMID- 1292639 TI - Chronic intraperitoneal infusion of low doses of tumor necrosis factor alpha in rats induces a reduction in plasma triglyceride levels. AB - 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. PMID- 1292640 TI - 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. AB - 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) PMID- 1292641 TI - Influence of surgery on in-vitro cytokine production by human monocytes. AB - 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. PMID- 1292642 TI - High serum levels of TNF-alpha after its administration for isolation perfusion of the limb. AB - 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. PMID- 1292643 TI - Interleukin 8 (IL-8) in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS. AB - 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. PMID- 1292644 TI - Critical sites: a semantic approach to protein sequences. Application to the HIV 1 envelope molecule. AB - 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. PMID- 1292645 TI - Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate. AB - 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. PMID- 1292647 TI - Effect of enkephalins on bone marrow cells. AB - 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. PMID- 1292646 TI - Cell-mediated immunity against HGP-30, a group-specific peptide of HIV p17 in individuals infected with the AIDS virus. AB - 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. PMID- 1292648 TI - Bromazepam-induced dystonia. AB - 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. PMID- 1292649 TI - Allotransplantation of canine pancreatic islets. AB - 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. PMID- 1292650 TI - In vitro growth of erythroid progenitor cells (BFU-E) and production of burst promoting activity (BPA) by T lymphocytes in patients with myelodysplastic syndromes. AB - 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. PMID- 1292651 TI - Radical tumor excision and cosmetic balance in the surgical treatment of breast carcinoma: biquadrantectomy. AB - 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. PMID- 1292653 TI - Thyroid hormone extraction by plasma exchange: a study of extraction rate. AB - 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. PMID- 1292652 TI - Characterization of a murine monoclonal antibody, 5D-4, reacting with pancreatic cancers and islets of Langerhans. AB - 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. PMID- 1292654 TI - Should there be a separate code of nomenclature for the protists? AB - 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. PMID- 1292655 TI - Papers presented at the 9th meeting of the International Society for Evolutionary Protistology. Paris, July 3-7, 1992. PMID- 1292656 TI - When is a family not a family? AB - 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. PMID- 1292657 TI - Detecting morphological convergence in true fungi, using 18S rRNA gene sequence data. AB - 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. PMID- 1292658 TI - Green algae and the evolution of land plants: inferences from nuclear-encoded rRNA gene sequences. AB - 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. PMID- 1292659 TI - An analysis of partial 28S ribosomal RNA sequences suggests early radiations of sponges. AB - 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. PMID- 1292660 TI - Quantization test of the evolution trend of Paleocosta pervinquieri (Ostracode) during a 10-million year period (Djebel-Dyr section, Paleogene, Algeria). AB - 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. PMID- 1292661 TI - Miocene variability of Calcidiscus gr. leptoporus and possible evolutionary relationship with another Coccolithaceae: Umbilicosphaera gr. sibogae. AB - 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. PMID- 1292662 TI - The impact of environment on ontogenesis variations in Ruggieria and Chrysocythere (Ostracoda). AB - 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. PMID- 1292663 TI - Unusual extrusive organelles in karyorelictid ciliates: an argument for the ancient origin of this group. AB - 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. PMID- 1292664 TI - Flagellar apparatus duplication and partition, flagellar transformation during division in Entosiphon sulcatum. AB - 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. PMID- 1292665 TI - Energy metabolism of ancestral eukaryotes: a hypothesis based on the biochemistry of amitochondriate parasitic protists. AB - 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. PMID- 1292666 TI - Matrix representation in reconstructing phylogenetic relationships among the eukaryotes. AB - 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. PMID- 1292667 TI - Eukaryote-eukaryote endosymbioses: insights from studies of a cryptomonad alga. AB - 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. PMID- 1292668 TI - The four genomes of the alga Pyrenomonas salina (Cryptophyta). AB - 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. PMID- 1292669 TI - Gene phylogenies and the endosymbiotic origin of plastids. AB - 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. PMID- 1292670 TI - The number of symbiotic origins of organelles. AB - 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. PMID- 1292671 TI - [The chemosensory support of feeding behavior in precocial and altricial mammals during ontogeny]. AB - 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. PMID- 1292672 TI - [Atypical endplate miniature potentials in the frog neuromuscular junction after modification of the intercellular matrix and osmotic exposures]. AB - 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. PMID- 1292673 TI - [The structural dynamics of vagus influence on the heart rhythm in exposures directed at altering the acting acetylcholine concentration]. AB - 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. PMID- 1292674 TI - [The effect of stimulation and blockade of the dopaminergic system on the choice of behavioral strategy by rats in the shuttle box]. AB - 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. PMID- 1292675 TI - [Adaptation to periodic hypoxia decreases ethanol consumption and abstinence related damages to the internal organs during withdrawal in chronically alcoholized animals]. AB - 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. PMID- 1292676 TI - [Diaphragmatic blood flow in hypoxia and hypercapnia]. AB - 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. PMID- 1292677 TI - [The content of mitochondrial and microsomal cytochromes in liver tissue in experimental drug-induced fatty hepatosis]. AB - 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. PMID- 1292678 TI - [The role of noradrenaline in regulating myocardial oxidative metabolism in rats with different resistances to hypoxia]. AB - 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. PMID- 1292679 TI - [The correlation of energy-consuming and energy-synthesizing reactions in rat hepatocytes in different O2-deficient states]. AB - 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. PMID- 1292680 TI - [The conjugation of preliminarily immunosorbent-immobilized 5B4D6 monoclonal antibodies with a chelating polymer]. AB - 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. PMID- 1292681 TI - [Ganglioside participation in the regulation of free-radical reactions in brain membranes]. AB - 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. PMID- 1292682 TI - [The effect of endothelin-1 on Na+/H+ metabolism in vascular smooth muscle cells]. AB - 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. PMID- 1292683 TI - [Calpains and cathepsin D from the damaged myocardium: the role of iodothyronines]. AB - 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. PMID- 1292684 TI - [The competition of serum amyloid protein and apoprotein E for binding with human serum albumin]. AB - 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. PMID- 1292685 TI - [The effect of sodium cyanate-modified hemoglobin oxygen affinity on the heat resistance of rats]. AB - 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. PMID- 1292686 TI - [The mechanisms of the neutrophil suppression of creatine kinase and aspartate aminotransferase activities in rat skeletal muscles]. AB - 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. PMID- 1292687 TI - [The anticoagulant properties of the endothelium studied by the standard venous occlusion test]. AB - 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. PMID- 1292688 TI - [The action of dipyridamole on megakaryocytopoiesis in regenerating and stationary bone marrow cell populations]. AB - 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. PMID- 1292689 TI - [The action of korazol on the defensive behavior of rats]. AB - 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. PMID- 1292690 TI - [The properties of the glucocorticoid-sensitive alkaline proteinases of target organs in rats]. AB - 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. PMID- 1292692 TI - [The hemodynamic and metabolic effects of 2-deoxy-D-glucose in waking Wistar rats]. AB - 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. PMID- 1292691 TI - [The normalizing effect of dalargin on the glucocorticoid and opioid levels of the blood in CBA and C57Bl/6 mice undergoing footshock stress]. AB - 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. PMID- 1292693 TI - [Antibody formation to morphine and neuromediators in morphinized rats]. AB - 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. PMID- 1292695 TI - [A comparative study of met-enkephalin effects on the secretion by murine lymphocytes of antibodies to different antigens]. AB - 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. PMID- 1292694 TI - [The immunomodulating activity of new muramyl dipeptide derivatives in vitro]. AB - 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. PMID- 1292696 TI - [The immunostimulating properties of cholecystokinin octapeptide and its fragments]. AB - 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. PMID- 1292697 TI - [Changes in the content of reduced glutathione in the liver of mice under the action of staphylococcal enterotoxin type A and lipopolysaccharide]. AB - 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. PMID- 1292698 TI - [The binding of pathogenic ligands by human placental erythrocytes]. PMID- 1292699 TI - [The stimulation of the bactericidal activity of human neutrophils by lymphoid cells activated by interleukin-2; the effect of inflammatory cytokines]. AB - 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. PMID- 1292700 TI - [The effect of a mite allergen on Na/H metabolic activity in peritoneal mast cells]. AB - 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. PMID- 1292701 TI - [A method for the primary biological assessment of the photodynamic activity of photosensitizers in a nontumor model in vivo]. AB - 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. PMID- 1292702 TI - [The oncogenic action of nonfibrous mineral dusts]. AB - 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. PMID- 1292703 TI - [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]. AB - 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. PMID- 1292704 TI - [The characteristics of Ehrlich carcinoma recurrence and metastasis]. AB - 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. PMID- 1292705 TI - [The chromosomal radiosensitivity of children whose parents were exposed to antitumor radiochemotherapy]. AB - 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. PMID- 1292706 TI - [A comparative analysis of the cerebral cortical proteins in rats with different sensitivities to hypoxia]. AB - 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. PMID- 1292707 TI - [A morphological evaluation of the action of collagenase from the king crab Paralithodes camtschatica on the experimental wound process]. AB - 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. PMID- 1292708 TI - [Structural changes in the central nervous system of dogs with a combined bilateral lesion of the carotid arteries]. AB - 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. PMID- 1292709 TI - HIV-associated tuberculosis in developing countries: epidemiology and strategies for prevention. AB - 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. PMID- 1292710 TI - Mass miniature X-ray screening for tuberculosis among immigrants entering Switzerland. AB - 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. PMID- 1292711 TI - Good concordance between two batches of new tuberculin in the Mantoux test. AB - 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. PMID- 1292712 TI - Comparative study of skin testing with PPD and new tuberculins by the WHO Mantoux test. AB - 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. PMID- 1292713 TI - Isoelectric focusing patterns of beta-lactamases in the rapidly growing mycobacteria. AB - 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. PMID- 1292714 TI - Tuberculosis surveillance and evaluation system in Portugal. AB - 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. PMID- 1292715 TI - Childhood tuberculosis and tuberculous meningitis: high incidence rates in the Western Cape of South Africa. AB - 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. PMID- 1292716 TI - Comparative antigenic analysis of Mycobacterium avium complex (MAC) isolates from AIDS patients. AB - 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. PMID- 1292717 TI - Mycobacterial lymphadenitis in Western Australia. AB - 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. PMID- 1292718 TI - Lymph node tuberculosis: 7-year experience in Veterans General Hospital, Taipei, Taiwan. AB - 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. PMID- 1292719 TI - Case-control study of the efficacy of BCG immunization against pulmonary tuberculosis in young adults in Santiago, Chile. AB - 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. PMID- 1292720 TI - 10-year assessment of treatment outcome among Cambodian refugees with sputum smear-positive tuberculosis in Khao-I-Dang, Thailand. AB - 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. PMID- 1292721 TI - Human tuberculosis due to Mycobacterium bovis: report of 10 cases. AB - 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. PMID- 1292722 TI - Spinal infection by Mycobacterium xenopi in a non-immunosuppressed patient. AB - 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. PMID- 1292723 TI - Auricular stimulation and acupuncture as an adjuvant to an anti-smoking programme: analysis of the results of a 1-year experience. PMID- 1292724 TI - Primary nasopharyngeal tuberculosis. PMID- 1292725 TI - Nosocomial transmission of multidrug-resistant tuberculosis between AIDS patients. PMID- 1292726 TI - Epidemiological mess? PMID- 1292727 TI - Scabies: not just a nuisance infection. PMID- 1292728 TI - Another view to blood and body substance precaution: 1988-91. AB - 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. PMID- 1292729 TI - Hospital outbreak traced to a case of Norwegian scabies. AB - 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. PMID- 1292730 TI - How to clean and maintain urinary leg bags: 'easy on the nose'. AB - 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. PMID- 1292731 TI - Results of CHICA-Canada survey of long term care infection control practitioners. AB - 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. PMID- 1292732 TI - [Relationship between health services for maternal and child health and working hours of public health nurses]. AB - 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. PMID- 1292733 TI - [Structure of communication between physicians and patients from the viewpoint of community health]. AB - 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. PMID- 1292734 TI - [Observation of sequential changes in results of oral glucose tolerance tests in individuals]. AB - 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. PMID- 1292735 TI - [The prevalence of diabetes mellitus and impaired glucose tolerance studied by 75 gram oral glucose tolerance test in a rural island population]. AB - 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. PMID- 1292736 TI - [A survey of body temperatures in the elderly and the thermal environment in nursing homes]. AB - 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. PMID- 1292737 TI - [Health status and care of the urban elderly]. AB - In order to investigate the health and care of the urban elderly, self administered anonymous questionnaires were sent to a sample randomly selected from the elderly 70 to 89 years of age, in 3 different areas (central, residential and suburban) in Wakabayashi-Ward in Sendai. Responses from 1,248 were returned by mail (response rate = 76.4%) and results were compared to the expected values estimated from the results of investigations conducted by the Ministry of Health and Welfare. 1) As for present addresses of the elderly, 94.2% were at home, 3.8% in hospitals, 0.7% in nursing homes, and 1.3% in other facilities. 2) Responses showed that 28.4% were suffering from hypertension, 5.6% from diabetes mellitus, 2.2% from strokes and liver diseases, with all of these percentages similar to the respective expected values. However, 12.7% were suffering from heart disease which was over twice the expected value. 3) Analysis of health habits showed that the percentages of the elderly who had "good sleep and rest", "nutritious meal", and "moderate exercise" were higher than expected. Only 2.3% did not practice good health habits, which was one sixth of the expected value. 4) As for meal habits of the elderly, 88.3% had three meals a day, and 33.7% made efforts to take less salty foods. 5) Dietary habits of the elderly indicated that 83.8% were frequent consumers of meat, fish and soybeans products, 62.3% vegetables, 51.0% sweet confectionery (significantly higher), 49.2% milk (significantly higher), 22.3% fried foods like tempura (significantly higher), and 22.3% salty vegetables (significantly lower).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292738 TI - [A study of falls experienced by institutionalized elderly]. AB - This study was conducted to determine what factors are related to falls, conditions contributing to falls and the associated injuries. Subjects who had lived in 3 institutions for the elderly in the western region of Shizuoka Prefecture were chosen. Subjects (n = 181) had an average age of 76.4 +/- 7.8 years, and all were interviewed regardless of their history of falls. For those who had experienced falls further interviews were conducted. The following results were obtained: 1) There were 64 subjects (35.4% of the subjects) who had experienced falls, some having experienced multiple falls (for a total count of 89 falls). 2) The frequency of falls of differed by sex or age was significantly. The frequency of females was significantly higher than that of males. The frequency for those in their 70's was lower than in other age groups. 3) At the time of experiencing falls the majority of subjects had hypertension, eye symptoms, insomnia, paralysis, functional restrictions, were going up or down stairs, working, and had difficulty reading characters in newspapers, had experiences of stumbling or need of medical attention within for the past 2 years. Results of this study showed that, while the use of tranquilizers or hypnotics were not statistically significant, they were closely connected to and increase in falls among the aged. 4) In the causes of falls, intrinsic factors figured in 34 (34.0%) cases, and the extrinsic factors in 66 (66.0%). 5) Both falls and fall-caused external injuries were higher among females than males. Furthermore, female subjects mainly suffered contusions and fractures while male subjects mainly suffered abrasions. PMID- 1292740 TI - [Adolescents cigarette use--how do we health education researchers approach the problem?]. PMID- 1292739 TI - [Prevention of hepatitis B in a hospital]. PMID- 1292742 TI - [Factors associated with the improvement of lifestyle among a middle and advanced aged male population]. AB - Factors associated with improvement of lifestyle (diet, smoking, drinking, exercise and health check-up) were studied among 3,503 males aged 40 or more, based on data obtained by two questionnaire surveys which were conducted at about a five year interval in a mountainous area of Aichi Prefecture. Age was positively associated with the improvement of every habit except for health check up. Developing diseases was associated with the improvement of every habit except for exercise, with strong associations existing between liver diseases and improvement in drinking habits and between diabetes and improved nutritional balance. Improved dietary habits was inversely associated with frequent use of instant foods and irregular eating habits. Moderation in eating was associated with a balanced diet, frequent intake of yellow/green vegetables, fats & oils, and non-smoking at the time of the initial survey. Cessation of smoking was positively associated with fruit intake and inversely associated with irregular meal times, number of cigarettes per day and alcohol intake at baseline. An increase in frequency of exercise was positively associated with consumptions of fruits and dairy products and inversely associated with frequent use of instant foods at time of the initial survey, while an increase in frequency of health check-up was observed among men who had a balanced diet. The improvement of each habit was associated with the improvement of one or more other habits. These results suggest that likelihood for improving lifestyle is higher among men who have a health consciousness and that improvements in these habits are independent. PMID- 1292743 TI - [A case-control study on factors relating to discontinuation of domiciliary care for the bedridden elderly in a metropolitan area]. AB - A case-control study was conducted to examine factors relating to discontinuation of domiciliary care for the bedridden elderly in Shinagawa-ku, Tokyo. Cases were bedridden residents aged 65 years and over who had abandoned home care and applied for admission to live in a special nursing home for the aged between April and September in 1990 after being recipients of welfare allowances for disabled elderly. Controls were bedridden residents who continued to be given home care and matched to cases by sex, age and beginning month of the receiving of allowances. Among 50 cases and 94 controls interviewed, we obtained responses from 31 cases (62%) and 60 controls (64%). The main results were as follows: 1. During the home-care period, ADL (activities of daily living) of cases, especially walking ability, deteriorated more severely than in controls. Night delirium also appeared more frequently in cases. 2. The primary caregivers of cases were older than those of controls. Remarkable differences between cases and controls were observed in the family structure, the number of family members and the number of sub-caregivers. Cases tended to live alone or live with a spouse only, and with smaller number of family members and caregivers. 3. Case lived more frequently in houses with small numbers of rooms and without rooms of their own. 4. As regards utilization of domiciliary care services, cases used dispatch of home helpers more frequently and used day services less frequently. PMID- 1292741 TI - [Prevention of cerebro-cardiovascular diseases by early intervention in youth]. AB - A significant number of youth have obesity, hypertension, hypercholesterolemia and diabetes mellitus which are major risk factors for C.V.D and I.H.D. and which frequently occur after maturity. Analysis of lifestyle factors show a strong relationship between a series of these factors, and life style practices as typified by time-saving, dietary practice such as convenience foods, insufficient exercises, as well as family history of C.V.D. Prompt establish next of a system for screening high risk children with these factors and a corresponding support system for guiding and instructing them, is indicated. Studies should be performed from the viewpoint of life-cycle health management for establishing an integrated examination system for circulatory diseases for screening to follow up. PMID- 1292744 TI - [Study on the relationship between toddler temperament and development (first report)--the correlation among toddler temperament, maternal perception and rearing environment]. AB - The purpose of this study is to clarify how a child's temperament and maternal perception influences the rearing environment. As the conceptual framework, we used A.J. Sameroff's transactional model and Miyake's conceptual model of mother and child. The following process was hypothesized: toddler temperament influences maternal perception, which in turn influences rearing environment under which children are developing. Questionnaires concerning toddler temperament, maternal perception and rearing environment were sent to mothers whose children were scheduled to receive 1 year and 6 months child health examinations, and results from 306 mothers and children who answered the questionnaires were analyzed. The results were as follows: (1) Child temperament showed a tendency to accord with maternal perception of how easy it is to handle him/her. (2) Maternal perception was related to rearing environment. (3) Temperamental characteristics were related to rearing environment. (4) While the influence of child temperament and maternal perception on the rearing environment was not shown to be strong, the hypothesized process of this study was supported to a certain degree. From these results, it appears that it is important to pay attention to a child's temperament as a contributing factor in the health practice of mother and child. PMID- 1292745 TI - [An outbreak of food poisoning suspected due to Aeromonas and characteristics of the isolated strains]. AB - On June 7, 1990, food poisoning with main symptoms of abdominal pain and diarrhea occurred in Inuyama City, Aichi Prefecture. From results of bacteriological examination, three kinds of mesophilic Aeromonas spp. were detected from patients, leftover foods, well water, and cookers, one of which was A. hydrophila which was shown to produce haemolysin thought to be the cause of the food poisoning. On the other hand, A. sobria and A. caviae isolated from various materials did not produce haemolysin. The latter two strains of mesophilic Aeromonas spp. did not produce any other enterotoxins. Therefore, it appears that the well water containing A. hydrophila, A. sobria and A. caviae polluted the foods, which then had caused the food poisoning. Of nine strains of A. hydrophila, five do not dissolve sucrose, and these are typed as serogroup O:22 or O:23. The other four strains dissolve sucrose, and these are typed as serogroup O:16. According to the drug sensitivity test, all of these nine strains of A. hydrophila were resistant to Ampicillin, Erythromycin and Cephaloridine. PMID- 1292747 TI - [A study on the distortion of distributions of delays in detecting pulmonary tuberculosis]. AB - It is reported that a cumulated percentage of the interval between the onset of symptoms and the first visit to a doctor (patient delay) and that between the first visit and diagnosis (doctor's delay) among pulmonary tuberculosis (TB) patients demonstrate a straight line on the log-normal probability paper. Factors influencing the straight line nature of these delays were analyzed. The samples consist of 454 patients who were diagnosed between 1986 and 1988, from the area served by the Kochi Chuo Health Center. They were divided into two groups; 125 patients detected due to the manifestation of additional symptoms related to TB while being treated for other diseases (group A), and 329 patients detected only after the onset of TB symptoms (group B). Results are as follows. 1) When considering all patients (group A+B), patient delay among cases found through positive examination of tubercle bacillus and the doctor's delay among cases whose bacillus examination was negative demonstrated a straight line. However patient delay among bacillus negative cases demonstrated a downward tendency and the doctor's delay among bacillus positive cases demonstrated a upward tendency on the log-normal probability paper. 2) In the B group, both the patient's and doctor's delay demonstrated virtually straight lines among both bacillus positive and negative cases. However, in the A group, a straight line among bacillus positive cases was demonstrated, while a downward tendency was revealed among the bacillus negative cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292746 TI - [Occupational skin hazards in hairdressers and their etiologic factors--results of mass health examination at health centers]. AB - From 1986 to '88, mass health examinations for skin disorders among hairdressers were performed in 4 Health Centers in Osaka Prefecture. Among 306 female hairdressers examined, the prevalence of skin lesions was 49.0%, consisting of skin lesions of hands and arms alone 22.9%, nail lesion alone 13.7%, and both 12.4%. Characteristic features of the skin lesions were dryness, roughness, thickening of epidermis, redness, hyperkeratinization, scales, desquamation, etc. In the case of nails, thinning, onycholysis, onychoschisis, pitting, transverse grooves and onychorexis were characteristic. The relationship between prevalence of skin disorders and site of lesions to history or category of work was studied. For the prevention of these skin hazards, improved chemicals, equipment, and hygienic education are necessary. Periodical health-checks including participation by a dermatologist, and health supervision should be continued with cooperation between Health Centers and beauty salons, because these businesses are principally small-size enterprises. PMID- 1292748 TI - [Visiting behavior to medical institutions of 26 intractable diseases patient receiving financial aid for treatment in Saitama Prefecture]. PMID- 1292749 TI - Uterine fibronectin mRNA content and localization are modulated during implantation. AB - Fibronectin mRNA and protein content were examined during embryonic implantation in the rat uterus. Content of total fibronectin mRNA at day 6 of pregnancy increased relative to the non-pregnant uterus. In contrast, fibronectin protein content of the subepithelial stroma was relatively decreased except in the region directly surrounding the lumen, and this fibronectin immunoreactivity was sensitive to hyaluronidase treatment. These changes are likely to reflect the degradation and subsequent remodeling of the previously stable uterine extracellular matrix in preparation for embryonic implantation. A+, B-, V + fibronectin mRNAs were present in both the non-pregnant and day 6 pregnant uterus with increased content of A+ and V+ fibronectin mRNAs in the latter. A + fibronectin mRNA was distributed throughout the endometrial stroma of the non pregnant uterus and content of the subepithelial stroma increased by day 4 of pregnancy, coincident with progesterone action on the endometrium. On day 6 of pregnancy, fibronectin mRNAs encoding the V95 and A regions were preferentially localized to the mesometrial zone of the subepithelial stroma. Accumulation of these mRNA splicing variants at the mesometrial zone was dependent upon decidualization, but the embryo was not required. Thus, there are two major changes in uterine fibronectin gene expression as a result of pregnancy: increased fibronectin mRNA content and mesometrial localization. These changes suggest a key function for fibronectin in implantation and imply the operation of a regulatory program of fibronectin gene expression which depends on hormonal sensitization and a nidatory stimulus. PMID- 1292750 TI - Expression of Hox 2.1 protein in restricted populations of neural crest cells and pharyngeal ectoderm. AB - A polyclonal antibody, alpha Hox 2.1a, was used to localize Hox 2.1 protein in presumptive neural crest cells and nodose ganglion of 8.5-10.0 day p.c. mouse embryos. The following results were obtained: (1) The nodose placode, in its epithelial state, first expresses Hox 2.1 protein at 9.0 d.p.c. By 9.5 d.p.c. presumptive migrating neuroblasts between the nodose placode and ganglion primordium also express Hox 2.1 protein. (2) At 9.5 d.p.c., presumptive crest cells lateral to the cephalic cardinal vein and within pharyngeal arches 4 and 6 are immunoreactive for alpha Hox 2.1a. In the arch 6 region, positive cells extend medially to a mesenchymal cell population on the lateral aspect of the foregut wall. (3) At 10.0 d.p.c., Hox 2.1 protein expression in putative crest cells is restricted to the arch 6 cell population. A similar staining pattern is seen using alpha Hox 2.1a with chick embryos. Comparison with the chicken embryo suggests that the Hox 2.1 positive cells in the pharyngeal arch and those on the lateral aspect of the foregut in the mouse embryo correspond to the caudalmost subpopulation of the circumpharyngeal crest (Kuratani and Kirby: Am. J. Anat. 191:215-227, 1991; Anat. Rec. 234:263-280, 1992). These results are consistent with a role for Hox 2.1 in pattern formation in the caudalmost region of the vertebrate head. PMID- 1292751 TI - Segregation and early dispersal of neural crest cells in the embryonic zebrafish. AB - We have exploited our ability to visualize and follow individual cells in situ, in the living embryo, to study the development of trunk neural crest in the embryonic zebrafish. In most respects, the development of zebrafish trunk neural crest is similar to the development of trunk neural crest in other species: zebrafish trunk neural crest cells segregate from the dorsal neural keel in a rostrocaudal sequence, migrate ventrally along two pathways, and give rise to neurons of the peripheral nervous system, Schwann cells, and pigment cells. However, some aspects of the development of zebrafish trunk neural crest differ from those of other vertebrates: zebrafish trunk neural crest cells are significantly larger and fewer in number than those in avian embryos and the locations of their migratory pathways are slightly different. This initial description of neural crest development in the zebrafish embryo provides the foundation for future experimental studies. PMID- 1292752 TI - Laminin expression in the mouse lung increases with development and stimulates spontaneous organotypic rearrangement of mixed lung cells. AB - The recent establishment of a role for laminin in mouse lung organogenesis (Schuger et al. 1990a,b, 1991) prompted us to study its expression in the developing lung. Laminin A and B chains were detected in the murine lung from the first hours of development onward. In situ hybridization of mRNA as well as SDS PAGE studies of lung cells in monoculture indicated that both epithelium and mesenchyme produce complete laminin molecules. Quantitative analysis of the in situ hybridization studies showed a gradual increase in laminin expression during development which was further supported by immunohistochemistry and ELISA. The overall pattern of expression suggested that the effects of laminin in morphogenesis were not restricted to a particular stage of development. Furthermore, the increase in expression during late development supported a role for the molecule in the fetal lung, which was not previously established. We next determined whether the increase in laminin production modulated the behavior of fetal lung cells as compared with their embryonic counterparts. We previously showed that organotypic pattern formation does not occur in cultures of mixed embryonic lung cells unless exogenous laminin is added (Schuger et al., 1990b). Organotypic pattern formation is the result of cell sorting into epithelial and mesenchymal compartments and further rearrangement in a pattern resembling the tissue of origin. In the present study, we demonstrated that organotypic pattern formation occurs spontaneously in cultures of mixed fetal lung cells, which express high laminin levels. Pattern formation was abolished by antibodies to laminin. These studies suggest a correlation between laminin expression and the ability of lung cells in culture to reproduce normal tissue patterns. We conclude that laminin is critical for epithelial-mesenchymal recognition and further morphogenic interaction during both the embryonic and fetal stages of lung development. PMID- 1292753 TI - Coordinate expression of IGF-I and its receptor during limb outgrowth. AB - The morphogenetic mechanisms involved in shaping the embyro are largely unknown. Previous studies from this laboratory suggest that the mesonephros promotes limb outgrowth in ovo in the chicken embryo and might be involved in early limb morphogenesis, since damage to the mesonephros results in truncated limbs. In limb bud organ cultures, the presence of the mesonephros promotes cartilage formation. This effect can be reproduced by exogenous IGF-I or prevented by blocking antibody to IGF-I. In order to examine the hypothesis that mesonephros derived IGF-I is involved in the early morphogenesis of the limb, we examined the spatial and temporal expression of IGF-I and type I receptor for IGF by in situ hybridization at stages when the onset of limb development occurs. The results show that neither transcript is detected at stage 13, prior to the appearance of the limb bud; but both transcripts are detected in the mesonephros at stage 14, an early stage in limb outgrowth. The hybridization signal in the mesonephros for both transcripts increases with development and signal was codistributed as well. At stage 18 the level of receptor transcripts detected in the flank relative to the limb decreased. Thus, the temporal and spatial patterns of expression of IGF I and its receptor are consistent with their involvement in the initiation of limb outgrowth and support the model that localized expression of a growth factor and its receptor can be involved in shaping the embryo. PMID- 1292754 TI - Paracrine/autocrine growth mechanisms in tumor metastasis. AB - The successful growth of metastatic tumor cells is due to their responses to local paracrine growth factors and inhibitors and their production and responses to autocrine growth factors. At early stages of metastatic progression, there is a tendency for many common malignancies to metastasize and grow preferentially at particular sites, suggesting that paracrine growth mechanisms may dominate the growth signals affecting metastatic cells. At later stages of metastatic progression, where widespread dissemination to various tissues and organs occurs, autocrine growth mechanisms may dominate the growth signals affecting metastatic cells. The progression of malignant cells to completely autonomous (acrine) states can ultimately occur, and at this stage of metastatic progression cell growth can be completely independent of growth factors or inhibitors. Various strategies have been developed to treat cancer that are based on the responses of malignant cells to growth factor or inhibitor analogs, anti-receptor antibodies, or antibody- or growth factor-toxin conjugates. Since the responses and expression of growth factor receptors can change during malignant progression, the development of cancer treatments using analogs of specific growth inhibitors or antagonists of growth factors, such as monoclonal antibodies or other agents, to block growth signaling mechanisms may only be useful at the early stages of malignant cancer progression before widespread metastasis of acrine cells occurs. PMID- 1292755 TI - Synergistic antiproliferative effects of the combination of interleukin-1 alpha and doxorubicin against human melanoma cells. AB - We have investigated the antiproliferative effects of recombinant human interleukin-1 alpha (IL-1) combined with the cytotoxic antitumor drug doxorubicin against A375 human melanoma IL-1-sensitive (C6) and IL-1-resistant (C5) clonal cell lines. Growth inhibition was assessed by the MTT assay, and C5 cells were 10 fold less sensitive to IL-1 than the C6 cells, but both cell lines were equally sensitive to doxorubicin. Synergistic antitumor activity between the two agents was evaluated by median effects/combination index analysis, and IL-1 and doxorubicin were strongly synergistic over a broad range of drug concentrations. The strongest synergism occurred when C6 cells were exposed to IL-1 prior to doxorubicin, and when C5 cells were pretreated with doxorubicin for 6 hr prior to IL-1 additions. An examination of various ratios of the two agents revealed a maximum 20-fold potentiation of doxorubicin, and a 30-fold potentiation of IL-1 median dose values in the combination compared to the median dose values obtained with doxorubicin or IL-1 alone. Doxorubicin treatment enhanced the binding and internalization of [125I]IL-1 after 24 and 48 hr at 37 degrees C, but IL-1 binding to cells incubated on ice was increased only marginally by doxorubicin pretreatment. Treatment of C6 cells with IL-1 for 24 hr did not alter the cellular accumulation of doxorubicin. A recombinant protein IL-1 receptor antagonist that binds to both the 80 kDa type I and the 65 kDa type II IL-1 receptors, blocked the cytostatic effects of IL-1 and abrogated the synergism with doxorubicin. In cells synchronized following release from aphidicolin block, doxorubicin caused a G2 + M accumulation, IL-1 alone had no effect, and the combination of both agents resulted in a G2 + M block similar in magnitude to that caused by doxorubicin alone. These results provide preclinical evidence that doxorubicin combined with IL-1 may be beneficial in the clinical treatment of malignant melanoma and possibly other types of solid tumors. PMID- 1292756 TI - Sequential therapy with chemotherapeutic drugs and liposome-encapsulated muramyl tripeptide: determination of potential interactions between these agents. AB - Three syngeneic murine tumor models were used to determine potential interactions between chemotherapeutic drugs and the synthetic liposome-encapsulated macrophage activator, muramyl tripeptide phosphatidylethanolamine (MLV-19835). Experiments were designed to maximize any additive toxicity of the simultaneous administration of MLV-19835 on the known myelosuppressive effects of doxorubicin, ifosfamide, and cisplatin. Treatment with these drugs resulted in diminished blood leukocyte counts, altered leukocyte differentials, and decreased hematocrits, but the systemic administration of MLV-19835 produced no additional deleterious effects. Myelosuppression normally observed at 2 weeks following treatment of mice with doxorubicin was prevented by combination treatment with MLV-19835. In addition, there was no interference of the antitumor activity of ifosfamide or doxorubicin against subcutaneous, kidney, and spleen tumors. These studies and the recent demonstration of the biological activity of MLV-19835 in phase II trials of osteosarcoma recommend clinical testing of these combined modalities. PMID- 1292758 TI - Reference listings in cancer research. PMID- 1292757 TI - Expression of glial fibrillary acidic protein in human medulloblastoma cells treated with recombinant glia maturation factor-beta. AB - Medulloblastoma, a common pediatric brain tumor, is a primitive neuroectodermal tumor which often displays neuronal and/or glial characteristics. We have investigated the consequences of treating cell lines derived from a human medulloblastoma with glia maturation factor-beta (GMF-beta), a protein found in mammalian brain. GMF-beta promotes growth arrest and morphological alteration of cultured glioma and neuroblastoma cells. The proliferation of medulloblastoma cells was arrested 24-48 hr after exposure to human recombinant GMF-beta. During the same period, treated cells acquired a morphology similar to that of mature astrocytes. By 72 hr, all treated cells bound an antibody against glial fibrillary acidic protein (GFAP), a distinguishing biochemical feature of mature astrocytes. Immunoreactivity was accompanied by de novo expression of GFAP mRNA. Our observations are the first demonstration of the induction of morphological and biochemical characteristics of mature astrocytes in cultured medulloblastoma derived cells by an exogenous factor. PMID- 1292759 TI - [Screening of cancer in Europe: current update]. PMID- 1292760 TI - [Tumor necrosis factor: pleiotropic cytokine]. AB - Originally described for its capacity to induce hemorrhagic necrosis of transplantable tumors in mice, TNF-alpha also exerts cytotoxic effects against some tumor cell lines in vitro. It is now known that TNF is an essential mediator of cellular immunity and a wide variety of biological activities of TNF in vitro and in vivo has been reported. TNF is an important mediator of inflammation and is involved during the pathogenesis of several auto-immune, infectious or cancer diseases. While some immunomodulatory properties of TNF have at least been partially elucidated, the biochemical basis of TNF cytotoxic action remains largely unknown. Furthermore, the molecular mechanisms of TNF susceptibility have yet to be clarified. Clinical studies with recombinant TNF as an anticancer agent are encouraging. Multiple phase I and phase II trials have been carried out without major therapeutic effect. In fact, TNF resistance and TNF-induced systemic toxicity are two major limitations for the use of TNF as an antineoplastic agent. The clinical application of human TNF remains an area of active research and innovative approaches such as gene therapy need to be elaborated. The elucidation of the process of lysis and the modulation of TNF resistance are crucial to the future development of TNF and its use in antitumor therapy. PMID- 1292761 TI - [Meta-analysis, tool for synthesis and observation]. PMID- 1292762 TI - [Retinoids and carotenoids in cancer chemoprevention trials]. AB - At the present time, cancer chemoprevention trials, especially non-randomised studies, constitute a large part of the scientific literature. Our purpose was to perform a critical analysis of the few randomised trials comparing a group treated with retinoids or carotenoids to an untreated control group or a placebo control group. Only one trial gave convincing results in favor of such chemoprevention, especially concerning the incidence of secondary cancer, at the cost of severe toxicity. Moreover, we have attempted to list the ongoing intervention trials which could provide details on the indications involved for such treatments. PMID- 1292763 TI - [Chemotherapy of malignant ovarian Brenner tumors. Review of the literature apropos of 2 histological complete remissions after polychemotherapy]. AB - The authors report two cases of malignant ovarian Brenner tumor treated by polychemotherapy, that had a complete histological response confirmed by a second look laparotomy. The review of the literature shows that complete responses are exceptional, either after mono- or polychemotherapy. PMID- 1292764 TI - [Adjuvant therapy of breast cancer with tamoxifen and endometrial carcinoma]. AB - Twenty cases of endometrial carcinoma are reported, observed in women who had received long term tamoxifen treatment as adjuvant therapy for breast cancer. Furthermore, a specific study was carried out on an homogeneous group of 790 women with an operable breast cancer, 318 receiving tamoxifen as adjuvant treatment. Five endometrium carcinoma were observed in the group under tamoxifen versus none in the other group. From an analysis of these cases, authors will carry out a case control study to evaluate the relative risk of endometrial carcinoma for patients under tamoxifen. They underline the importance of gynecologic follow up procedures for all women receiving this endocrine therapy. PMID- 1292765 TI - [Epidemiology of breast cancer in men]. AB - Incidence data for male breast cancer from 34 selected cancer registries in different parts of the world are presented. The geographic variation in incidence is similar to that observed for female breast cancer, resulting in a strong correlation between their respective rates, although certain populations have higher rates for male breast cancer than expected from the female incidence, notably Israeli Jews and blacks in the United States. It seems that both environmental factors (acting by the intermediary of endogenous oestrogens excess) and genetic predisposition play a role in determining the epidemiological profile of male breast cancer, as they do for cancer of the female breast. PMID- 1292766 TI - [Departmental compilation of histoprognostic data in senology. Apropos of campaign screening in Bouches-du-Rhone]. AB - In January 1990 a registry for cases of breast cancer occurring in the Bouches-du Rhone area was set up in conjunction with a screening programme for women over 50 years of age. The aim of this study was to compare histoprognostic findings of unscreened patients (A) with a palpable lesion, screened patients (B) with or without a palpable lesion and self screened patients (C) registered for clinically occult mammary carcinoma. The histoprognostic criteria studied were: histological type, tumor size, prognostic grade and axillary lymph node involvement. Of the 2,478 surgical procedures registered, 1,125 involved women over 50 years of age including 47% with malignant disease. Only 3.7% of screened patients presented intraductal carcinoma compared with 1.17% to 18.2% of unscreened A or self-screened C patients. The incidence of minimal infiltrating breast cancer smaller than 10 mm varied widely from 17.3% in A patients to 33.7% in B patients and 51.4% in C patients (P < 0.001). The incidence of histoprognostic grade III tumors ranged from 17.9% in A patients to 10% in B patients and 4.3% in C patients (P < 0.007). Lymph node involvement decreases from 41% in A to 28% in B patients and 23% in C patients (P = 0.01). Based on our data, 41.9% of screened patients were in the most favorable prognostic category, ie intraductal carcinoma or infiltrating carcinoma less than 10 mm or grade I and no lymph node involvement, versus only 26.1% of A patients and 60.9% of C patients (P < 0.0001). Information of the incidence, pathology of interval tumors in previously screened women will be evaluated in the future. This first study underscores the necessity for this kind of registry to evaluate the histoprognostic profile year by year of a breast cancer screening campaign. PMID- 1292767 TI - [Acute cholecystitis: percutaneous transhepatic drainage]. AB - Despite emerging endoscopic techniques for treatment of gallbladder diseases the operative cholecystectomy is the treatment of choice in acute cholecystitis. Percutaneous cholecystostomy is an alternative treatment modality in poor surgical risk patients. In 19 out of 36 patients with percutaneous cholecystostomy no subsequent cholecystectomy was performed. A long-term observation of these 19 patients showed normal function of the gallbladder in ultrasound studies, thus percutaneous drainage can be a definitive treatment for acute cholecystitis in selected cases. PMID- 1292768 TI - [Percutaneous removal of residual calculi of the bile ducts by T-drainage tract]. AB - Percutaneous instrumentation under fluoroscopic control via the T tube tract is a minimally invasive technique to remove retained bile duct stones after cholecystectomy. 23 of 25 patients were treated successfully with this method. Two patients needed either percutaneous transhepatic stone-removal or repeat surgery because his residual calculus could neither be removed percutaneously nor endoscopically. In standard situations, the calculi were removed quickly and easily under outpatient conditions. Impacted and large calculi had to be mobilized and fragmented prior to their removal. One patient developed fever, another a mild, transient pancreatitis, no serious complications were observed. In large series, the success rate is 86-95%, the complication rate 3-5%, and the mortality rate 0-0.1%. A relative drawback of the percutaneous technique is the waiting period of approximately 4 weeks which is required for tract maturation. However, this inconvenience is acceptable if we consider that the risk of the percutaneous procedure is less than with endoscopic retrograde sphincterotomy. Therefore, we still favour a primary percutaneous radiologic approach to remove retained bile duct stones. PMID- 1292769 TI - [Roentgen findings in T-drainage--results of 311 patients]. AB - Postoperative T Tube cholangiographies of 311 patients from 1980 to February 1992 were evaluated by studying the patient histories and x-ray examinations. Most frequent questions concerned residual stones and papillary occlusion. Most frequent pathological findings were dilatation of the choledochus and of the bile ducts, residual stones and paravasations. Fistulas, abscesses and signs of cholangitis rarely occurred. Dilatation of the choledochus alone did not lead to further treatment. Papillary occlusion was treated by leaving the T drain in situ, patients with occlusion and residual stones were treated by papillotomy, litholysis or lithotripsy. Only 5 patients with necrotizing pancreatitis and abscess had to be reoperated. T tube cholangiography, which at the beginning of the study was a routine postoperative control with minor complications, will surely be applied less frequently in the future due to advances in endoscopy. PMID- 1292770 TI - [Sonography and biliary extracorporeal shockwave lithotripsy]. AB - Ultrasound is an indispensable tool for preliminary diagnosis ('filter function'), during treatment ('monitoring function') and in the followup examinations ('follow-up function') after shock wave lithotripsy of gallstones. It permits rapid and reliable assessment of the therapeutic outcome and early identification of complications, which experience to date has shown to be rare. PMID- 1292772 TI - [Renal arteriovenous fistula after kidney biopsy: color Doppler ultrasound and angiography diagnosis with embolization using the same procedures]. AB - Arteriovenous (AV) fistulas are an uncommon but well-known complication of percutaneous renal biopsies. Recent studies suggest that Color Doppler Sonography is useful in the identification of post-biopsy renal AV fistulas. AV fistulas may cause persistent hematuria, hypertension, or high-output cardiac failure. In these cases surgical ligation or angiographic embolization is necessary. In this study we report a case of post-biopsy renal AV fistula identified with Color Doppler Sonography and Angiography. The renal AV fistula also was embolized with a platinum microcoil under angiographic and ultrasonographic guidance. PMID- 1292771 TI - [Magnetic resonance tomography of the hepatobiliary system: indications, limitations and outlook]. AB - In a prospective study we examined the diagnostic value of MRI and MR cholangiography (MRC) in patients suffering from hepatobiliary disease. By using hepatobiliary contrast media (Mn-DPDP, Gd-BOPTA), sensitivity and specificity of MRI were significantly increased. In 65 patients we comparatively analyzed the diagnostic results of MRI and MRC versus ultrasound, CT and invasive techniques such as ERCP. We conclude that the use of MRI and MRC improves the diagnostic evaluation of patients with hepatobiliary disease. PMID- 1292774 TI - [American College of Rheumatology 56th Annual Scientific Meeting Atlanta, 11-15 October 1992. New aspects of imaging procedures in rheumatology]. PMID- 1292773 TI - Urinary extravasation from the kidney of recurrent renal cell carcinoma. AB - A man presented with recurrent renal cell carcinoma, complicated with acute pyelonephritis, 3 months status post partial nephrectomy. He underwent cystourethroscopy and a bilateral retrograde pyelogram, then was referred for a Tc-99m DTPA renal study; the images showed an initial photon-deficient area of the right kidney being gradually filled-in by radiotracer with further extension laterally, indicating urinary extravasation. 16 days later this area was aspirated, yielding 5 ml of yellowish fluid with clots consistent with necrotic tumor and pus. PMID- 1292775 TI - [1st Seminar on the trans-jugular intrahepatic portosystemic stent shunt (TIPS) (1st Freiburg TIPS Seminar). Freiburg University Medical Clinic, 26 September 1992]. PMID- 1292776 TI - Deriving a 67-nucleotide trans-cleaving ribozyme from the hepatitis delta virus antigenomic RNA. AB - RNAs derived from the genomic and antigenomic hepatitis delta virus are capable of self-cleavage, and thus have the potential for serving as ribozymes in a trans cleaving reaction. Because the catalytic core of such an enzymatic RNA was not evident from phylogenetic data, we took a step-wise approach to identifying the core, reducing the RNA in size, and characterizing various properties for each size class. Thus, a 186-nucleotide antigenomic RNA (termed Ag180) was found to be capable of cleaving well in 20 M formamide (Smith and Dinter-Gottlieb, 1991), and this unusual stability in formamide was lost by reducing the 3' end of the molecule, leaving a 140-nucleotide RNA (Ag 140). Both RNAs showed only intramolecular cleavage at a wide range of concentrations, and a number of conformers could be seen in the Ag140 RNA, some of which were resistant to cleavage at 37 degrees C. Since Ag140 could not cleave in 20 M formamide, the 5' and 3' termini of Ag180 were truncated and produced Ag5-84, which cleaved to 100% at 37 degrees C in less than 0.25 min. Internal deletions of the Stem IV region resulted in Ag5-73, still capable of efficient cleavage, although with a lessened stability in formamide. A trans-cleaving enzyme-substrate pair was finally derived from this RNA, and it consisted of a 67-nucleotide enzyme that cleaved a 13-nucleotide RNA substrate. PMID- 1292778 TI - Characterization and minimization of cellular autofluorescence in the study of oligonucleotide uptake using confocal microscopy. AB - Intrinsic autofluorescent signals can interfere with extrinsic fluorophore signals when living cells are viewed under a confocal laser scanning microscope. The general pattern of this endogenous fluorescence is initially diffuse and cytoplasmic, but it can redistribute and intensify to become punctate and perinuclear as cells age. To reduce the contribution of autofluorescence when tracking the location of an extrinsic fluorophore, such as a fluorescently labeled oligonucleotide, laser power settings, aperture settings, laser scanning rates, pH buffering environments, and excitatory wavelengths can be modulated. Decreasing laser power settings and aperture sizes, increasing laser scanning rates and excitatory wavelengths, and surrounding cells in a pH buffer all act to delay the signal transformation. In addition, the presence of an exogenous fluorophore can hasten the autofluorescent redistribution and intensification when compared to similar untreated cells. PMID- 1292777 TI - 9-Aminoellipticine-derivatized alpha- and beta-oligodeoxyribonucleotides targeted to the cap of beta-globin mRNA: hybridization to natural and engineered mRNA, inhibition of translation, and improved effect of tandem chains. AB - We studied the duplex stability and the antimessenger activity of 9 aminoellipticine-5'-functionalized alpha- and beta-anomeric DNA sequences complementary to the first 14 nucleotides of the rabbit beta-globin mRNA. The duplex formed by the beta-conjugate with the natural mRNA target possessed a marginally better stability to that of the duplex formed by the unfunctionalized compound, as measured by the thermal elution. The alpha-conjugate did not anneal to native mRNA, possibly due to the interference of the 9-aminoellipticine with the cap structure and, unlike the beta-adduct, was practically inactive as inhibitor of translation in a cell-free system. However, it did hybridize to an RNA construction containing the beta-globin mRNA plus an additional 50 bases in 5'. Surprisingly, translation from this construction was inhibited by the alpha species in spite of the nonvicinity of the target to the cap. Both alpha and beta conjugates hybridized to a DNA 14-mer of the same sequence as that targeted onto the mRNA. Thermal denaturation and fluorescence spectroscopy showed that the drug brought no considerable stabilization to the duplex, the linker presumably being unfavorable to intercalation. An increased stability of the complex and a higher inhibitory effect on cell-free beta-globin translation were obtained with two contiguous beta-oligomers of which one was functionalized. PMID- 1292779 TI - Inhibition of murine leukemia viruses by nuclease-resistant alpha oligonucleotides. AB - We studied the antiviral activity of nuclease-resistant alpha-anomeric oligonucleotides. An alpha-oligonucleotide (20-mer) targeted to the primer binding site (PBS) of murine retroviruses inhibited viral spreading. The inhibition only occurred when the cells had been electropermeabilized in the presence of the oligonucleotide. The PBS sequence is involved in reverse transcription and in translation. The data suggest that the oligonucleotide could perturb reverse transcription activity. Thus, either the oligonucleotide induced a decrease in initiation or it inhibited the extension of the minus or plus strands DNA during reverse transcription. These results show that reverse transcription may be an interesting target for antisense oligonucleotides. PMID- 1292780 TI - Nonspecific suppression of [3H]thymidine incorporation by "control" oligonucleotides. AB - Phosphodiester oligonucleotides are rapidly degraded in spleen cell cultures. The present studies were conducted to determine whether thymidine released from degradation of such oligonucleotides could be reutilized and compete with [3H]thymidine incorporation, thereby causing nonspecific inhibition of "proliferation" assays. Our studies in mitogen-stimulated mouse spleen cells demonstrate that "control" oligonucleotides that contain thymidine can cause more than 90% inhibition of [3H]thymidine incorporation. This inhibitory effect was generally dependent on the location of the thymidine within the oligonucleotide: oligonucleotides that had 3'-terminal thymidine(s) caused more suppression than those in which thymidines were at the 5' end. All oligonucleotides caused a modest but variable inhibition of [3H]uridine incorporation. Furthermore, [3H]thymidine incorporation was partially inhibited even by oligonucleotides that did not contain thymidine. We propose that investigators who use [3H]thymidine incorporation assays to assess antisense effects do so with caution. It may be prudent to use control oligonucleotides with the same number and location of thymidine bases and to confirm [3H]thymidine incorporation assays with other measures of cell proliferation. PMID- 1292781 TI - Cytotoxicity of a selected series of substituted phenols towards cultured melanoma cells. AB - Substituted phenolic compounds were previously shown to exhibit cytotoxicity towards epithelial cells in the presence of the enzyme tyrosinase as a result of the formation of their quinone products. Seventeen of these compounds were tested for cytotoxic properties towards three different melanoma cell lines. The compounds were split into four groups of phenol derivatives, A; alkoxyethers, including 4-hydroxyanisole (4HA), B; oxyethers derivatized at the acyl side chain, C; oxyethers derivatized at the phenol, and D; acyl thioethers. Toxicity was determined by total cell counts after 3 days exposure to the compounds. Large reductions in cell numbers were observed with 4HA (the methoxy-), ethoxy-, propoxy and iso-butoxyethers of group A and the methyl- and propyl thioethers of phenol of group D. Derivatization of the ethoxy- and propoxy side chains (group B) did not seem to increase the cytotoxic effects, as determined by cell counts. Compounds of group C, which need intracellular esterase activity to release the phenols, showed moderate toxicities. Toxicity of certain compounds was confirmed by LDH release into the culture medium and by increased trypan blue uptake of cells exposed to the compounds. Flow cytometric investigations of cells after exposure for 24 h revealed that most compounds caused an increase in the proportion of cells in G1 phase. A complete accumulation of cells in S-phase was observed after exposure to 4-ethoxyphenol. Inhibition of DNA synthesis was also shown by inhibition of bromodeoxyuridine incorporation. The results presented show that phenolic compounds exhibit cytotoxic properties towards melanoma cells some of which may be mediated by tyrosinase activity. Toxicity of the compounds was shown to be exerted during DNA replication but their toxic action may also be due to membrane damage and inhibition of cell metabolism. PMID- 1292782 TI - Purification and analysis of growth regulating proteins secreted by a human melanoma cell line. AB - Supernatants of a human malignant cell line established from a CNS metastasis, contained several proteins with putative growth regulating functions. BioGel P-10 gel filtration chromatography, reverse phase HPLC purification, and amino terminal sequencing of purified peptides resulted in characterization of beta 2 microglobulin (beta 2M, 10 kD), ubiquitin (6 kD), and tissue inhibitor of metalloproteinases 2 (TIMP-2, 21 kD). In addition, CNBr cleavage and purification of resulting peptides revealed diazepam binding inhibitor (DBI, 8 kD) and melanoma inhibiting activity (MIA, 11 kD). The secretion of beta 2M as part of the HLA-class I complex may be related to impaired autologous anti-tumour immune function; ubiquitin may play a role in activation or deactivation of extracellular proteins or cell-cell interactions. As HTZ-19 cells respond in a dose-dependent manner to midozolam, DBI may interfere with growth regulation mediated by diazepam receptor sites. In a collagenolytic assay, TIMP-2 interfered with metalloproteinase functions, which are required for degradation of collagen type IV and organotopic metastasis. MIA is clearly associated with a proliferation inhibiting effect on HTZ-19 cells. In conclusion, although this tumour shows a degree of progression, several proteins with putative functions at different cellular levels were identified, related to proliferation as well as to the type of metastasis. PMID- 1292784 TI - The relationship of tumour antigens to normal proteins, with special reference to albumin-like melanoma antigens. PMID- 1292783 TI - Treatment with high dose mouse monoclonal (anti-GD3) antibody R24 in patients with metastatic melanoma. AB - R24 is a mouse IgG3 monoclonal antibody that reacts with the ganglioside GD3 expressed by melanoma cells and other cells of neuroectodermal origin (e.g. adrenal medulla). Antitumour activity of R24 was demonstrated in initial phase I and pilot trials, but treatment was limited by urticaria at cumulative doses of 400 mg/m2. A trial exploring intensification of the dose of R24 was conducted in eight patients. Planned doses of R24 antibody were 800 and 1200 mg/m2 over 6-8 days by continuous i.v. infusion. All patients received concomitant therapy with hydroxyzine hydrochloride and cimetidine to minimize urticaria. One patient developed anaphylaxis, after which no further therapy was given. All patients developed peripheral blood lymphopenia and marked decreases in serum complement values during treatment, suggesting depletion of two possible effector mechanisms of the antitumour effects of R24. A vascular leak syndrome, manifested by weight gain, oedema and hypotension, was evident in seven patients during the initial 24 36 h of treatment. Serum sickness syndrome was observed in six of seven evaluable patients between days 5 and 8, coincident with the onset of the human anti globulin response to R24. One patient given 1200 mg/m2 had a minor response (38% reduction in pelvic nodes) lasting 12 months. There was no detectable increase (by immunohistochemical staining) in deposition of R24 within tumour sites at doses used in this trial compared to that observed at doses of 240 and 400 mg/m2. The maximum tolerated dose was 800 mg/m2. Dose-limiting toxicity was manifest as reversible hypertension with end-organ symptoms (chest pain or visual field defects) in patients treated with a dose of 1200 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292785 TI - Identification of a 66 kD heat shock protein (HSP) induced in M-14 human melanoma cells by severe hyperthermic treatment. AB - Following severe hyperthermic treatment M-14 cells synthesize at high rate a new protein of about 66 kD, in addition to the three well known major HSPs (HSP 28, HSP 70 and HSP 90). This 66 kD protein is constitutively expressed at low levels and its rate of synthesis is not enhanced by mild hyperthermic exposures (40 degrees C for 2-4 h; 42 degrees C for 1-3 h), sufficient to induce the three major HSPs. The 66 kD protein is induced whenever the thermal dose administered to cells attains a threshold, roughly corresponding to a 50% reduction in survival. The 66 kDa protein is not induced by a variety of compounds (disulfiram, arsenate, cadmium) able to elicit a stress response in M-14 cells, as indicated by enhanced synthesis of the three major HSPs. Once induced by a treatment at 45 degrees C for 15 min, the rate of synthesis of the 66 kD protein remains above the control level for 16-20 h during recovery from the stress, while the synthesis of HSP 70 is shut off between 8 and 12 h. Immunoblotting and immunoprecipitation studies showed that the 66 kD protein shares immunological determinant(s) with HSP 70. Pulse-chase experiments demonstrated that the 66 kD protein is not a degradation product or a late post-transcriptional modification of HSP 70. It is proposed that the 66 kD protein is a previously unrecognized heat shock protein (HSP 66), characterized by an unusually high threshold for its induction. PMID- 1292786 TI - Cerebral metastatic melanoma: correlation between clinical and CT findings. AB - Thirty patients with malignant melanoma and cerebral metastases confirmed by CT were studied. Metastases were classified according to their size: < or = 1 cm (group A), 1.1-4 cm (group B), and > 4 cm (group C), in order to assess the clinical course of the disease and predict the response to treatment with fotemustine. Group B lesions were the most common, independent of the site of the primary tumour, except for patients with rectal melanoma. Group C metastases were least common and were usually solitary. Asymptomatic patients usually had group A metastases, whereas those with non-specific complaints, hemisyndrome or neurobehavioural changes usually had group B metastases. The time from diagnosis of the primary tumour to discovery of disease in the CNS was significantly longer for those who had group A lesions, compared with those who had groups B or C lesions (P < 0.0001). Solitary lesions usually belonged to groups B or C, whereas multiple lesions belonged mainly to groups A or B. All the responders to fotemustine has mainly cortical, group A or group B lesions. Patients with group C lesions or leptomeningeal spread did not respond to fotemustine. Our findings suggest an association between the size of the cerebral metastatic lesion from malignant melanoma and clinical parameters characteristic of tumour behaviour. PMID- 1292787 TI - Fotemustine--an advance in the treatment of metastatic malignant melanoma. AB - Although chemotherapy has been generally of limited clinical benefit in the treatment of metastatic malignant melanoma (MMM), fotemustine (FM) is a newly developed drug which is active against this disease. Twenty-four patients with histologically proven MMM were treated with fotemustine, with or without dacarbazine (DITC) according to different phase II trials. In the first schedule, three patients received FM alone on days 1, 8, 15 followed by a 5-week rest period. The second schedule consisted of FM administered on days 1 and 8 alternating with DTIC on days 15 and 16, followed by a 5-week rest period (19 patients). The third schedule, given to two patients, consisted of DTIC followed 4 h later by FM. The overall response rate was 8.3%. Response in those who were treated with alternating drugs, included one partial response (PR) in the brain which lasted 4 months, and one PR in brain metastases with complete response (CR) in lymph nodes for 4 months. Clinical and radiological evidence of regression was observed mainly in brain metastases (22.2%), reflecting the intracerebral activity of the drug. It seems that fotemustine is superior to any other drug currently available in the treatment of these metastases. PMID- 1292788 TI - The role of regional isolated perfusion in the eradication of melanoma micrometastases in the inguinal nodes: a comparison between an iliac and femoral perfusion procedure. AB - Regional perfusion therapy of melanoma is followed by an apparent decrease in lymph node metastases. When regional isolated perfusion is performed by cannulating the blood vessels at the iliac level, at least the middle and distal parts of the inguinal nodal zone are included. This is not the case with femoral perfusion. These two types of perfusion were therefore compared to determine whether iliac perfusion eradicates micrometastases present in the inguinal nodes. The regional node recurrence rate and time to regional node relapse of 97 patients treated with iliac perfusion were compared with those of 20 patients who received femoral perfusion. Prognostic factors such as sex, MD Anderson stage of disease, Breslow thickness and Clark level of the primary melanoma, and number of nodules of those with recurrent melanoma were equivalent in both groups. All patients were perfused with melphalan under normothermic conditions during the period 1978-1990. Five of 20 patients (25%) receiving femoral perfusion and 31 of 97 patients (32%) receiving iliac perfusion (P = 0.7, chi 2 test) developed inguinal node metastases after a median period of 25 (8-40) and 19 (2-71) months, respectively (Mann-Whitney U test, P = 0.9). There was no statistically significant difference in the 5-year survival rate (55% versus 62%, respectively; log rank test P = 0.5). Since no advantage could be seen in terms of reduction of inguinal node relapse for iliac perfusion, it is concluded that perfusion of the distal nodes is not the major cause of reduction of regional node metastases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292789 TI - [Hepatitis B in Wallis: results of a seroepidemiological survey]. AB - A sero-epidemiological survey was conducted on Wallis Island, in the South Pacific, from July 1988 to May 1989. A random sample from the general population was examined. 672 sera were tested for HBs antigen and anti-HBc antibody. Analysis of the data showed that there was little, if any, transmission from mother to newborn; serological markers seemed to be acquired during the first years of life, before the age of 15 years. After 15 years, seropositivity rate is stabilized at 85% for one and/or the other of the two markers. The seropositivity rate is 39% for the HBs antigen alone. A protocol to vaccinate infants less than one year is proposed. PMID- 1292790 TI - [Analysis of new criteria for increasing the specificity of commercial Western blots]. AB - We examined the frequency of serum cross-reactivity on Western blot for HIV1 and HIV2. 661 patients with tuberculosis in Abidjan, and 4,899 asymptomatic persons for HIV1 and HIV2 infections were tested. All specimens positive on ELISA for HIV1 or HIV2 were further characterized by synthetic peptide based tests. Confirmed positive samples were tested by HIV1 and HIV2 specific Western blot criteres utilisis. Dual serologic reactivity on synthetic peptide tests was significantly more frequent in HIV positive patients with tuberculosis than asymptomatic subjects. Positive HIV1 Western blots were seen in 61%-86% of specimens positive for HIV2 only on synthetic peptide tests. [Cross-reactivity, to HIV2 Western blots by HIV1 positive specimens was significantly more frequent in patients with tuberculosis than in asymptomatic subjects.] Using recently recommended criteria for HIV1 and HIV2 Western blot interpretation (presence of 2 env bands) reduced the overall proportion of HIV1 positive specimens having a positive HIV2 Western blot from 39% to 14% and HIV2 positive specimens having a positive HIV1 Western blot from 31% to 8%. PMID- 1292791 TI - [Resurgence of yaws in Central African Republic. Role of the Pygmy population as a reservoir of the virus]. AB - The authors present the results of a clinical (framboesia) and serological (TPHA and VDRL) investigation aimed at defining the reservoir of virus of yaws in the Lobaye area (southwest of CAR) out of which the disease spreads in spite of previous mass treatment campaigns. The Lobaye focus is still active because we found among the pediatric population under the age of 15 years, 5.6% contagious skin lesion and 19.6% VDRL+. In this area with contact between nomadic Pygmies and sedentary ethnic groups, the observed level of clinical and serological attacks suggested that the pygmie population, as previously described, makes up the principal focus of yaws. For every 1 case found through clinical examination, 3.5 cases VDRL+ and 4.8 cases TPHA+ are found through serological examination. This proportion indicates that clinical screening alone is not sufficient to evaluate the endemic yaws level in a population. PMID- 1292792 TI - [Neurosyphilis in Guinea. Retrospective study of 82 cases hospitalized at the CHU of Conakry]. AB - The authors report the semeiology of 82 (61 male, 21 females) neurosyphilis cases in patients, admitted into hospital at the CHU of Conakry, in the service of neurology and psychiatry. These cases were confirmed by serological reactions in the sweat and the neurolymph-spinal fluid. PMID- 1292793 TI - [Trachoma in the Sabou area (Burkina Faso). An epidemiological investigation]. AB - Little is known about the epidemiology of trachoma in the Mossi plateau of Burkina Faso and the recent drought could have modified the transmission of the disease. A study population of 82,187 was surveyed using a cluster sample technique. A total of 1,841 people in 108 compounds were included in 18 villages. Data concerning trachoma were collected during six weeks of fieldwork in July 1991, during which local health workers were trained in trachoma and primary health care in ophthalmology. Active trachoma prevalence rises in infancy to reach a peak of about 13% (95% CI 3-23) in the 2 to 5 years old age groups, and then falls to less than 2% prevalence in 30 to 49 age group. Trachoma scarring is almost non-existent and trichiasis was not seen. Active disease was significantly more prevalent in female (prevalence ratio = 1.97, 95% CI: 1.34-2.90) and this difference was present from the age of 3 years. Active trachoma above the age of 30 was more likely to be intense than follicular (p < 0.001, Fisher's exact test). Because of a low prevalence of active disease and because trichiasis is absent, trachoma is not a major health problem in the Sabou area, Burkina Faso. Girls are more affected by active disease than boys and inflammatory trachoma in adults are usually intense in this setting. PMID- 1292794 TI - [Current status of knowledge on the epidemiology of rickettsiosis in Africa]. AB - Rickettsioses have been reported all over Africa. Serologic investigations have been driven using non specific methods as Giroud microagglutination and Weil Felix test which led to numerous false positive. This explains the difficulties encountered in the evaluation of the prevalence of such diseases in Africa. However, three recent studies made in Tunisia, Central Africa and Zimbabwe show that seroprevalence of spotted fever group rickettsiae infections is close to 45% using MIF as reference method. New technics as Western and Line immunoblotting and RFLP PCR should allowed to new studies and revision of epidemiologic data on rickettsioses in Africa. PMID- 1292795 TI - [Imported malaria in Brest hospitals from 1981 to 1990]. AB - From 1981 to 1990, 96 confirmed hospital cases of imported malaria occurred in Brest. An important increasing of the annual number was observed in 1986. A high proportion of infection was due to Plasmodium falciparum, mainly from black Africa. Most of the patients was French young men, without or with inadequate chemoprophylaxis. Every case of malaria due to P. falciparum appeared during the 2 months following their return from an endemic area. Two patients had a clinical profile of visceral evolutive malaria and 5 a cerebral malaria. Three patients died. PMID- 1292796 TI - [Toxoplasmosis in Gabon. Results of a seroepidemiological investigation]. AB - A toxoplasmosis sero-epidemiological inquiry was effected with 2,324 sera collected from Libreville, Lebamba, Makokou, Lastourville and Woleu-Ntem. All the sera were first screened through Pastorex toxo (Diagnostics Pasteur). Those with more 8 IU/ml and 267 sera with less 8 IU/ml were then assayed by ISAGA (bioMerieux) for IgM. The results of ISAGA must be interpreted with carefulness for natural agglutinins are frequent in this population. The acquisition of immunity is precoce and more of 60% have a serology positive from ten years old. There was no difference between sex. PMID- 1292797 TI - [Cysticercosis in the province of Kayanza (Burundi)]. AB - Prompted by the diagnosis of two cases of cysticercosis in patients from the same province of Burundi, we conducted a study in this area to determine the cysticercosis incidence rate in this area of Burundi. Patients having presented with more than two convulsive seizures were studied. All of them usually eat pork. Diagnosis was established with the 3 following criteria: positive ELISA reaction in blood and/or CSF; presence of cystercus in subcutaneous node. Cysticercosis was diagnosed in 40 of the 98 investigated patients, 25 presenting a neurocysticercosis. PMID- 1292798 TI - [Electroencephalographic study of trypanosomes in meningoencephalitic stage of human African trypanosomiasis from Trypanosoma brucei gambiense before and after treatment with DL-alphadifluoromethyl- ornithine hydrochloride monohydrate (DFMO)]. AB - The aim of the study was to assess effects of DFMO (an inhibitor of polyamine biosynthesis) on waking electroencephalogram (EEG) of 25 patients at meningoencephalitic stage of human african gambiense trypanosomiasis (HAT), six of whom having been previously treated with and considered refractory to Melarsoprol. DFMO was administered intravenously at dose of 400 mg/kg/day for 14 days, followed by oral treatment at dose of 300 mg/kg/day for 21 days. EEG data were performed before, then 15 days after the end of the therapy. Initially tracings presented diversified abnormalities which have been classified into four groups: intermittent delta waves/generalised delta waves/low voltage background/paroxistic activities. Control recordings showed an improvement, but as for Melarsoprol tracings not returned completely to normal patterns. In most of the patients therapy was associated with clinical disorders improvement and in all but one with disappearance of trypanosomes. Marked amelioration in recordings of the patient who presented trypanosomes in LCR samples, suggest he was responsive to the treatment and perhaps therapy did necessitate continuation? The use of EEG investigation during treatments as a supervision way of patients with trypanosomiasis is discussed. PMID- 1292799 TI - [Phlebotomus perniciosus Newstead, 1911 naturally infected by promastigotes in the region of Nice (France)]. AB - The authors report the results of investigations in Nice from July, 16 to August, 3, 1991. The 2,098 phlebotomes captured represent three species: Phlebotomus perniciosus, Phlebotomus ariasi and Sergentomyia minuta. Two species: P. perniciosus and P. ariasi are infected with promastigotes. About 4% of dissected females are parasited. This is the first description in France of P. perniciosus infected. PMID- 1292800 TI - [Anopheles paludis: important vector of malaria in Zaire]. AB - An entomological study was carried out on the transmission of malaria in the Bandundu region, Zaire, during the dry season (July and August 1991). Five Anopheles species were recorded: Anopheles paludis, A. gambiae, A. funestus, A. moucheti and A. nili. A paludis was the dominant species and represents 55.1% of the total; the average number of A. paludis bites per man/day was 4.2. The sporozoite index was 6.2%; the inoculation rate due to A. paludis was h = 0.26, 1 infective bite each 4 days. A. paludis plays an important role with A. gambiae and is considered as one of the main vectors of malaria in this region. PMID- 1292801 TI - [Application of a new transport and storage material for improving the quality of drinking water in rural African areas]. AB - Although boreholes in rural african areas deliver safe drinking water, there is a daily consumption of water polluted by fecal bacteria. Contamination occurs during transport, storage and domestic allocation of water. This is directly attributable to ignorance of the rules of hygiene, and the use of traditional jars ineffective in maintaining water quality. Their replacement with more modern recipients and the initiation of sanitary education markedly decrease bacterial water contamination, however, WHO standards which define portable water are rarely attained. In fact, it seems that established WHO conditions can only be achieved with piped water or after chemical disinfection. PMID- 1292802 TI - [Epidemiology of Tinea capitis in Bangui (Central African Republic)]. AB - In Bangui (Central African Republic) an epidemiological survey making use of cluster sampling has been performed. Prevalence rate is not very high in Bangui (3.4%). Boys are more infected than girls. Both in rural and urban area prevalence rates are decreasing with age. Microsporum langeronii has been identified in 98% of case. PMID- 1292803 TI - [Epidemiologic aspects of whooping cough in a village of the central district of Kolokani in Mali]. AB - Epidemiologic aspects of a whooping cough outbreak are studied in a village of a rural precinct of Kolokani in Mali. The survey shows that the village as been contaminated by two children coming from Bamako, an urban center. Spreading of the epidemic is due to the lack of suitable therapy and vaccination. Seventeen cases are noticed within 83 children aged 0 to 13 years (20.5%) from October 12th, 1988, to January 22nd, 1989. The attack rate is the same in males and females. Knowledge, attitudes and practices of the population to face whooping cough are noted. Measures are proposed for therapy and prevention. PMID- 1292804 TI - [The effect of the alkylating carcinogen dipin on the proliferation, the level of polyploidy development and on micronucleus formation in a population of parent and newly formed hepatocytes]. AB - In the process of hepatocarcinogenesis induced by dipin and partial hepatectomy in mice, initial hepatocytes are gradually replaced with a population of newly formed hepatocytes which originate from oval cells (Radaeva, Factor, 1990). It has been shown that the increase in hepatocarcinogenesis duration (2-11 weeks) along with the intensification of oval-cell reaction are accompanied by a progressive injury of cell genome in the initial hepatocyte population. This injury manifests itself by an accumulation of cells with micronuclei as well as by the development of high levels of polyploidy and aneuploidy. In the initial parenchyma, clastogenic and aneuploidizing effects of dipin are maximally pronounced at the stage of appearing hepatocyte nodules which consist of newly formed hepatocytes (8-11 weeks). By this time the proliferative pool comprises 83 92%, the amount of aberrant cells increases in average from 7 to 50%, and the indices of average nuclear ploidy in population enhance 6-8 times as compared with the average level of polyploidy in normal parenchyma. The quota of binuclear cells without micronuclei abruptly falls while the quota of binuclear cells with micronuclei and nuclear bridges increases reaching 3/4 of the total amount of binuclear cells. Binuclear cells with nuclear bridges comprise about one third of binuclear cells with micronuclei. At the stage of hepatocytic nodules (8-11 weeks after induction), the population of newly formed hepatocytes is characterized by the absence of morphologically damaged cells and of cells with micronuclei, a low incidence of binuclear cells (1-3%), and a high value of proliferative pool (83 96%). PMID- 1292805 TI - [The peroxisomes of eosinophilic leukocytes]. AB - Functional properties of peroxidase-containing granules (peroxidasosomes) of eosinophiles are discussed. Findings are reported on the activities of peroxidase systems and of non-enzymic cationic proteins which occur in the eosinophilic peroxidasosomes in normal state and in various pathological states as well as their antimicrobial and antiparasitic activities. PMID- 1292807 TI - [Saprotrophic microflora as a producer of biologically active substances for the purpose of microbial saprotrophic pharmacotherapy]. AB - A problem of utilizing the microflora producing biologically active substances with a view to elaborating a microbial pharmacotherapy is discussed. The principle of this kind of therapy is to arrest pathological processes and to correct biochemical processes in the organism by means of "beating up" the strains-producers of biologically active substances. Substances secreted by strains-producers, are capable to suppress the growth of pathogenic microflora and malignant tumors as well as to correct physiological and pathological processes, may be utilized in future for a microbial saprotrophic pharmacotherapy depending on indications. PMID- 1292806 TI - [The antimicrobial proteins and peptides of neutrophilic leukocytes]. AB - Findings suggesting a vast variety of non-enzymic cationic proteins and peptides in human and animal leucocytes are reported. These cationic proteins and peptides demonstrate their antimicrobial and cytotoxic properties due to their detergent characteristics and their capacity to change the permeability of cellular wall and membrane by electrostatic interactions. Information on their homology with some serine proteases is presented. PMID- 1292808 TI - [An experimental study of the mechanisms of precopulatory isolation between 3 genetic forms of the house mouse in the genus Mus]. AB - Under experimental conditions, possible mechanisms of precopulatory isolation were studied in house mice of there forms: Mus musculus musculus, sympatric M. spicilegus, and allopatric hybrid population of M. m. domesticus x M. m. musculus. In these experiments, the animals were placed in pairs (a male and a female in state of estrus) on a neutral territory. Nine combinations of matching were used. No pronounced mechanisms were found to prevent the copulation of partners of different forms. The factor analysis has revealed the dependence of different forms of social interactions between potential sexual partners upon three factors: taxonomic position of female, taxonomic position of male, and variant of matching. It was shown that the behaviour of female was one principal determinant of the development of events during the experiment. PMID- 1292809 TI - [An electron microscopic study of retinal development and pathogenesis in mutant CBA/J mice with hereditary retinal degeneration]. AB - Electron microscopic study of the neural retina pathogenesis was carried out on mice CBA/J in comparison with corresponding process in substrain CBA/Ki (Caley et al., 1972). A difference in terms of the pathology development was found between substrains CBA/J and CBA/Ki. It was shown that, in CBA/J, the retinal degeneration begins later than in CBA/Ki. As distinct from the latter, CBA/J proceeds to increase the thickness of outer nuclear and plexiform layers as well as the number of membranous discs of rod outer segments (ROS) between P10 and P12. In the retina of mouse CBA/J, pathologic alterations of the outer nuclear layer and the inner segments of photoreceptors precede the ROS destruction. It was found that the pigment epithelium is capable to phagocytize membranous discs of ROS in mouse CBA/J at P10 and P12. In CBA/J, the mitochondria in inner segments of photoreceptors begin to decay at P10; by P12, the amount of such segments reach 40%. At P12, the number of pycnotic nuclei (6%) in the outer nuclear layer coincides with the number of inner segments with dense degenerative cytoplasm. At P15, the state of retina as evaluated by the extent of far advanced degeneration of the outer nuclear layer is equalized in mice of both substrains. From P10 to P15, macrophages which phagocytize membranous discs of ROS are present in the interphotoreceptor space of CBA/J. The administration of PABA solution (7.5 x 10(-3) mg/g) daily from P1 to P9 or from P1 to P11 and with subsequent fixation at P10 and P12 respectively exerted no effect on the rate of retinal pathogenesis in mouse CBA/J. The causes of revealed differences in the development of retinal pathology between CBA/Ki and CBA/J are discussed as well as the causes of the absence of PABA effect on the retina of mutant mouse CBA/J. PMID- 1292810 TI - [A trial of the enzyme nuclease S1 for the recognition of defects in the secondary structure of DNA]. AB - In order to develop an adequate method for quantitative determination of age related defects of DNA secondary structure in somatic cells, the testing of enzyme nuclease S1 ("Sigma") was carried out. The conditions have been selected under which this enzyme revealed all single-stranded breaks and did not induce nonspecific breaks in DNA. It was shown that homopurine-homopyridine blocks of DNA capable of changing to H-form hypersensitive to S1, were not detected with the enzyme in the selected conditions. PMID- 1292811 TI - [Defects in the secondary structure of DNA recognizable by nuclease S1 and their possible role in the aging of mammalian somatic cells]. AB - The amount of defects in DNA secondary structure recognized by nuclease S1 and their localization by sequences of various nucleotide composition were studied in relation to the age factor. It was established that a significant twofold increase in defects of DNA secondary structure was observed in hepatic cells of very old (30 months and older) intact mice only, as well as in radiation-induced acceleration of aging at the age 19 months. The prevailing localization of the defects of DNA secondary structure has been demonstrated in those sequences which were enriched with AT pairs by 3% (as compared with the average level). It was concluded that the mentioned defects of DNA secondary structure are not the cause of aging. Nevertheless they can play an essential role in the process of irreversible destruction of genome in the terminal phase of aging. PMID- 1292813 TI - Bibliometric analysis as a measure of scientific output. PMID- 1292812 TI - [Changes in the count of large granular lymphocytes in the blood of virtually healthy persons depending on sex and age]. AB - The maintenance of large granular lymphocytes (LGL) in peripheral blood of 30 healthy donors has been studied. The mean value was 5.5 +/- 0.4% spreading from 2.4% to 10%. Healthy men had a higher level of LGL maintenance than healthy women (5.8 +/- 0.4% vs 3.6 +/- 0.7% respectively). It was found that the amount of LGL in male peripheral blood increased with age while the parameter spread decreased. PMID- 1292814 TI - Why patients choose to purchase a hearing aid privately. AB - A questionnaire survey was undertaken of patients who had recently purchased a private hearing aid. They were asked their reasons for choosing a private aid in preference to an NHS aid. Cosmetic considerations and the failings of Health Service provisions were the most commonly cited reasons. PMID- 1292815 TI - Simplified measurement of auditory filter shapes using the notched-noise method. AB - The shape of the auditory filter at a given centre frequency can be estimated by measuring the threshold for detecting a sinusoid presented in a spectral notch in a noise masker, as a function of notch width. Laboratory studies using this method have typically been based on threshold measurements for between 13 and 19 notch widths. In this note, we describe how both the overall sharpness and asymmetry of the auditory filter in hearing-impaired subjects can be estimated with reasonable accuracy using only five notch widths. This considerably reduces the testing time needed, making it possible to apply the method in clinical testing. PMID- 1292816 TI - The period evoked potential: a rapid technique for acquisition of phase-locked responses to continuous pure-tone stimulation. AB - In view of the current audiological need to obtain rapidly recorded and objective threshold information, particularly for frequencies below 1 kHz, we have developed an evoked potential technique based on the frequency following response. The technique involves the acquisition of a single captured epoch of EEG containing phase-locked responses to 1000 cycles of a continuous pure-tone stimulus. The captured epoch is partitioned into segments representing the responses to single cycles of the stimulus. The segments are then averaged to produce the period evoked potential. The process takes less than five seconds. PMID- 1292817 TI - The effect of posture on three objective audiological measures. AB - This study examines the effect of posture on click evoked otoacoustic emissions, tympanic membrane displacement, and travelling wave velocity obtained using the auditory brainstem response. Statistically significant changes with posture were observed for each technique. The changes in evoked emission and tympanic membrane displacement measurements were comparable with those reported by previous experiments. Travelling wave velocity measurements were shown to be sensitive to inferred posturally-induced changes in labyrinthine fluid pressure of around 150 mm saline. There was no statistically significant correlation between posturally induced changes measured by the three techniques. It is suggested that different mechanisms are responsible for the posturally-induced changes observed for the three techniques. PMID- 1292818 TI - Non-organic hearing loss in young persons: transient episode or indicator of deep seated difficulty. AB - Depressed auditory thresholds without evidence of organic hearing loss are observed in a small percentage of children and young adults. Several studies suggest that non-organic hearing loss (NOHL) is a manifestation of, or reaction to stress. Proposed treatments range from ignoring the apparent hearing loss through the use of psychotherapy and/or counselling to confronting the individual with evidence to prove that there is no real loss of function. Few studies report on long-term outcome. Thirty-eight subjects who had been diagnosed more than six and up to twenty-seven years ago as having NOHL were identified from records. Efforts were made to determine if there was any evidence of longer term effects. Nine were untraceable. Of those reviewed one was established as a malingerer; five had concurrent speech problems; one was possibly dyslexic; five were or had been under psychiatric care. These findings suggest that NOHL may, in some individuals, indicate underlying problems that merit detailed investigation and treatment. PMID- 1292819 TI - Syllabic compression: effective compression ratios for signals modulated at different rates. AB - Compression circuits are being used increasingly in hearing aids to reduce the dynamic range of signals. Their performance is usually characterized by: (1) the threshold sound level above which the compression starts to operate; (2) the compression ratio, which is the change in input level (in dB) required to achieve a 1 dB change in output level; and (3) the attack and release times over which the signal is integrated to determine the necessary gain change. In many practical situations, the effective compression ratio obtained with dynamically varying signals such as speech is less than the compression ratio obtained using standard test signals (slow square-wave modulation with large modulation depth). This article describes the effective compression ratios achieved with sinusoidal modulation, as a function of modulation rate, level relative to the compression threshold, compression ratio and time constants. The effects of compression on a typical speech signal are also discussed. PMID- 1292820 TI - Bias in scoring auditory brainstem responses. AB - ABR waveforms from 50 multi-handicapped children were analysed by nine judges in an investigation of scoring bias. Prior to estimating threshold for each subject, the judges were provided with either true or false ABR thresholds. This preliminary information was true in 25 of the cases and false in the other 25. The same ABR waveforms were evaluated one week later, but true/false biasing thresholds were reversed. Results revealed that while the more experienced judges were more accurate in their assessments, they were not necessarily less biased. The effects of bias were more predominant in those cases where the estimation of threshold was the most difficult. PMID- 1292821 TI - Effects of the fitting parameters of a two-channel compression system on the intelligibility of speech in quiet and in noise. AB - These experiments were carried out to assess how accurately the gains and compression ratios in a two-channel compression system needed to be set. We used as a research tool a laboratory version of a two-channel full-dynamic-range compression system. The system was initially adjusted to suit each hearing impaired subject according to the manufacturer's recommendations. Then, further adjustments were made to ensure that speech stimuli were both audible and comfortable over a wide range of sound levels. Finally, the settings of the gains and compression ratios were systematically varied from the adjusted values and the effects of this on the intelligibility of speech in quiet and in noise (12 talker babble, levels of 65 and 75 dB SPL) were measured. The results indicated that speech reception thresholds (SRTs) in quiet were significantly adversely affected by decreases in low-level gain. However, SRTs in noise were relatively unaffected by changes in low-level gain. An exception occurred at the higher noise level used, where increases in the low-level gains (with corresponding increases in compression ratios) had a significant adverse effect on the SRTs. It is concluded that, provided excessive low-level gains (associated with high compression ratios) are avoided, the main criteria for fitting such a system should be listening comfort (i.e. achieving an acceptable tonal balance, and avoiding uncomfortably loud sounds) and an appropriate value of the threshold for detecting speech in quiet (which should be a little below 50 dB SPL). PMID- 1292822 TI - Diaries of tinnitus sufferers. AB - Nine tinnitus sufferers kept daily diaries of their tinnitus experiences for up to three months. Levels of the loudest and quietest tinnitus and tinnitus annoyance were moderately highly correlated with each other and weakly correlated with the degree of sleep disturbance. Fluctuations in tinnitus sensation were frequent and associated with higher perceived levels and annoyance. Results were complicated by individual differences in tinnitus and lifestyle. PMID- 1292823 TI - Estimation of the loudness of tinnitus from matching tests. AB - To correct for the influence of recruitment when the loudness of tinnitus is measured by a balance test in an ear with sensorineural hearing loss, an averaged loudness function was devised, which converts the sensation level (SL) of tinnitus into an estimate of the effective loudness level. This is essentially the same as a phon scale except for the difference in reference level, and is defined as the equivalent SL of the tinnitus as if measured in an ear with a bone conduction threshold of 0 dB HL at a frequency between 500 Hz and 4000 Hz. Using this function, the median estimated loudness of tinnitus from 301 randomly selected patients was 15 dB 'effective loudness level' with a maximum of more than 60 dB. A nomogram was made for clinical use to determine the effective loudness level easily from the SL of tinnitus and the bone-conduction HTL of the test ear. Although somewhat approximate, the effective loudness level is considered to be an unbiased loudness estimate of tinnitus under the condition that only the SL of tinnitus and the bone-conduction HTL are available, and makes it easier to appreciate the actual loudness compared with a complex loudness unit such as on the sone scale. PMID- 1292824 TI - A hearing survey in patients awaiting cataract operation. PMID- 1292825 TI - [4-year experience of the Warsaw Center for Home Oxygen Therapy]. AB - Long-term oxygen therapy (LTOT) became a routine in the treatment of severe respiratory failure and cor pulmonale. Four years experience of the LTOT in Warsaw is presented. From 237 patients referred 172 were qualified for treatment. Majority--130 (76%) suffered from COPD. The rest of the group presented with pulmonary fibrosis, tb sequelae, bronchiectasis, kyphoscoliosis or chronic pulmonary thromboembolic disease. The mean oxygen breathing time averaged 14.5 H/day. Seventy two patients that is 42% of treated group died. The most frequent (63%) cause of death was respiratory failure. No adverse effects of LTOT were observed. PMID- 1292826 TI - [Effect of home oxygen therapy on patients with chronic obstructive lung diseases]. AB - Effects of 4 year of long-term oxygen therapy (LTOT) in 130 COPD patients were evaluated. All suffered from severe airways obstruction (FEV1 = 0.84 l), hypoxaemia (PaO2 = 55 mm Hg) and pulmonary hypertension (PAP = 29 mm Hg). The mean oxygen breathing hours averaged 15.2 h/day. Forty seven patients (36%) died during the observation period. LTOT did not prevent the progress of respiratory insufficiency-fall inc C and FEV. However it stabilized pulmonary arterial pressure and haematocrit. It was found that FEV1 < 0.76 l, PaO2 < 52 mm Hg, PAP > 30 mm Hg and oxygen breathing hours < 12/day bear risk of early death despite LTOT. The variables correlated best with survival were FEV1 and PaO2. PMID- 1292828 TI - [Effect of short-term home oxygen therapy on pulmonary artery pressure does not predict the survival of patients with chronic obstructive lung disease]. AB - We wanted to verify if the acute effect of oxygen on pulmonary arterial pressure (PPA) is related to survival on LTOT as was suggested recently in the literature. We studied 46 COPD patients qualified for LTOT. The acute effects of O2 on pulmonary haemodynamics were assessed by pressure and flow measurements before and after 30 mins of O2 breathing via 28% Ventimask. Thirty nine patients reacted with a fall of the mean PPA of less than 5 mm Hg. These were termed nonresponders (NR). In seven patients mean PPA fell > 5 mm Hg. They were called responders (R). After the initial investigations patients were followed up on LTOT for 2 years or until death. During two years of LTOT 15 patients died (12 from NR and 3 from R groups). The first two years survival rate was 69% in NR and 57% in R groups respectively. We conclude that survival on LTOT is not related to the acute effect of oxygen on the pulmonary arterial pressure in COPD patients investigated in the steady-state period of the disease. PMID- 1292827 TI - [Quality and results of year-long home oxygen therapy in Poland]. AB - Accuracy of qualification to LTOT and the results of one year of treatment were assessed in 12 regional centres in Poland. 390 patients with advances respiratory failure entered the study. There were 305 patients with COPD and 85 patients with other chronic lung diseases. The accuracy of qualification to LTOT in Poland is satisfactory--2/3 of patients were accepted to treatment with severe hypoxaemia (PaO2 55 mm Hg), the remainder with moderate hypoxaemia (PaO2 = 56-65 mm Hg) and signs of tissue hypoxia. After one year of treatment 6.5% of patients did not need LTOT and 13% stopped to fulfill the single entry criterion still needing treatment. PMID- 1292829 TI - [Effect of tobacco smoking on pulmonary function in employees of the Institute of Tuberculosis and Lung diseases in Warsaw]. AB - The effects of smoking habit on pulmonary function was studied prospectively (from 1987 to 1991) in a group of the staff in the Institute of Tuberculosis and Lung Diseases in Warsaw. The prevalence of smoking was the lowest among physicians (42% in 1987 and 24% in 1991). Nurses smoked more--51% in 1987 and 41% in 1991. A positive trend in quiting smoking was noted especially among physicians, nurses and technicians. Pulmonary function test were normal in all studied groups. The most pronounced decreases in lung function were noted in smokers. PMID- 1292830 TI - [Home oxygen therapy in the world and in Poland]. PMID- 1292831 TI - [Evaluation of the relations between exercise tolerance, dyspnea and pulmonary function in patients with chronic obstructive lung diseases]. AB - We studied 53 patients with severe COPD (FEV1 0.92 +/- 0.40 1, PaO2 61 +/- 9 mm Hg), aged 58 +/- 9 years, to assess the relationship between ability to exercise (6 MWD), dyspnea and baseline lung function parameters. Dyspnea at rest (D1) and during exercise (D2) was evaluated using VAS. During exercise dyspnea increased by 41 +/- 28, and oxygen saturation (StcO2) decreased from 92 +/- 3% to 84 +/- 9%. The fall in the StcO2 of more than 3% was observed in 42 patients (79%). We found that 6 MWD significantly correlated with the FEV1, VC and maximal dyspnea during exercise. There was no correlation between exercise tolerance and resting PaO2, PaCO2, severity of dyspnea at rest and the increase in dyspnea during exercise as well as with the resting and exercise StcO2 and the fall in StcO2 during walk. Dyspnea at rest and during exercise significantly correlated with air flow limitation and StcO2 at rest, during exercise and the exercise decrease in StcO2. There was a significant correlation between the fall in StcO2 during exercise and blood gases at rest. No relationship between the fall in StcO2 and the increase in dyspnea during exercise was found. PMID- 1292832 TI - [Dyspnea at rest and after exercise and the mental status of patients with chronic obstructive lung diseases]. AB - Thirty two patients with severe COPD were studied. We evaluated relationships between their psychological status, lung function parameters, exercises tolerance (6 MWD test) and dyspnea at rest and exercise (visual analogue scale). Patients demonstrated increased level of anxiety and psychological tension. In nearly half of the patients depression, low self-esteem and disbelief in the efficiency of therapy were observed. The correlations between the psychological status and the exercise tolerance hasn't been found. The correlation between the high level of depression and impairment of the lung function was found. The high increase in dyspnea score during exercises was connected with low self-esteem, although at rest the dyspnea level in those patients was low. PMID- 1292833 TI - [Regulation of respiration in patients with sleep apnea syndrome]. AB - 20 obese men with OSAS were examined. Polysomnography confirmed this diagnosis. In the daytime pattern of breathing, mouth occlusion pressure (P0.2) and ventilatory responses during CO2 rebreathing test were evaluated. Lung function indices were within normal limits except decreased value of MEF 25 and slight hypoxaemia (Pa0.2 -67 +/- 6 mm Hg). In comparison to control subjects the patients with OSAS when awake had increased ventilation, Vt/Ti ratio and P0.2. This suggests increased inspiratory neuromuscular output in daytime. During CO2 rebreathing test the whole ventilatory and P0.2 response lines were shifted to the left but the slopes of these lines were within normal limits. We conclude that the control of breathing in OSAS patients is changed in comparison to healthy subjects with normal weight. PMID- 1292834 TI - [Test of nonspecific bronchial hyperreactivity to water mist in patients with atopic bronchial asthma]. AB - 22 males with atopic asthma in clinical remission and 22 healthy males were evaluated. The age of the 44 males ranged from 19 to 23 years. Atopy was diagnosed in patients with a characteristic medical history, positive skin prick tests and elevated serum IgE levels. All patients underwent a bronchial provocation test to distilled water mist. The aerosol was produced in a ultrasonic nebuliser (Thomex) at a speed of 2 ml/min. All spirometric tests were carried out using Pneumoscreen (Jaeger) before and after inhalation of 2, 6, 12, 20 and 30 ml of distilled water. A positive test was defined: as a decrease of FEV1 by/or more 10%, decrease of MEF50 by/or more 25% and increase of Raw by/or more 30%. A positive test was found in 7 patients with atopic asthma after inhalation of 20 ml of distilled water. Sole lowering of FEV1 was seen in 11 asthmatics. In the control bronchial constriction could not be induced. PMID- 1292835 TI - [Cough-syncope syndrome in tracheobronchomalacia]. AB - A 40-year-old man, referred for treatment of syncope due to cough, was found to have generalized tracheobronchomalacia. The diagnosis was based on an abnormal collapsibility of the trachea and bronchi on bronchoscopic examination. The detailed investigations confirmed the diagnosis of cough-syncope syndrome due to tracheobronchomalacia. Based on this case the causes, symptoms and possible treatment of those clinical entities are discussed. PMID- 1292837 TI - [Dyspnea in chronic obstructive lung diseases]. PMID- 1292836 TI - [Threatened hypometabolic crisis in a patient with hypothyroidism, pneumonia and respiratory insufficiency]. PMID- 1292838 TI - Food allergens as causative factors of respiratory, skin and gastrointestinal allergy confirmed by skin prick test and specific IgE and IgG4 FAST in children. PMID- 1292839 TI - Screening test and further particular allergological diagnosis in children. PMID- 1292840 TI - Determination of total and specific IgE to antigens from food allergens in children with atopic dermatitis using fluorimetric method of 3M Diagnostic Systems. PMID- 1292842 TI - Analysis of hypersensitivity to airborne allergens in children with bronchial asthma using FAST. PMID- 1292841 TI - Fluorimetric method of 3M Diagnostic Systems in determining the role of inhaled allergens in atopic dermatitis in children. PMID- 1292843 TI - Specific bronchial hyperreactivity in patients with asthma in anamnesis and elevated serum levels of total IgE and/or of allergen-specific IgE. PMID- 1292844 TI - Determination of total and allergen-specific IgE in patients with bronchial asthma. PMID- 1292845 TI - Allergen-specific IgE antibodies in circulating immune complexes in allergy to house dust and plant pollens. PMID- 1292846 TI - Humoral response in asthma patients sensitive to house dust mites during specific immunotherapy with Alutard SQ. PMID- 1292847 TI - Occurrence of high serum levels of allergen-specific IgG4 to antigens from common food allergens in blood donors. PMID- 1292848 TI - Study on specific immunotherapy with the aid of 3M Diagnostic Systems' tests. PMID- 1292849 TI - Effect of specific immunotherapy on IgE immune complexes in seasonal allergic rhinitis. PMID- 1292850 TI - Monitoring of specific immunotherapy with 3M Fluoro-FAST in insect sting sensitive patients. PMID- 1292851 TI - Prevalence of serum specific antibodies to Borrelia burgdorferi antigens in persons from region of high risk of tick bites. PMID- 1292852 TI - Lyme disease in clinical practice. PMID- 1292853 TI - Evaluation in vitro of T-cell mediated immunity in patients with atopic disease. Effects of thymic hormone therapy. I. Phenotypic features of peripheral T lymphocytes. PMID- 1292854 TI - IgE in children with adverse reactions to food. PMID- 1292855 TI - Repression of the E. coli lactose operon by cooperation between two individually unproductive "half-operator" sites. AB - Two remote and weak lac regressor binding sites can be used jointly to repress the synthesis of beta-galactosidase in E. coli, while they cannot separately. When this result is discussed in reference to the various modes of cooperation between the sites, it supports with a new approach a model implying the simultaneous binding of lac repressor to both sites with the formation of a DNA loop. In connection with this point, we present a new strategy to detect cooperative interactions in vivo, based on the asymmetry of the DNA binding site, formally equivalent here to a half-site, heterodimerization of the protein, and influence of orientation of the sites on repression at short and long distance. PMID- 1292856 TI - [Biological significance and interpretation of the corpulence index BMI (Body Mass Index)]. AB - A study of the corpulence of young French men between the age of 18 and 20 has proved the existence of a biological constant between the height and the weight, bringing a new significance to the Body Mass Index. The elaboration of a new index BMC (BMI corrected), allows us to know with precision the underweight or overweight of any individual. PMID- 1292858 TI - Fair pay and then some: how to retain your staff. AB - It may be stating the obvious, but the bottom line is this: treat staff the way you would like to be treated yourself. Appreciate, respect, recognize and reward them. Behavior that is appreciated gets repeated. The easiest way to find out if your team is happy is to open up the channels of communication. Relieve yourself of the guesswork by asking them what they want. If you can't give them everything at once, you may be able to satisfy at least some of the items on their wish list. And when you address their needs and wants, you'll be rewarded with more loyalty and commitment than you'd ever have expected. You will be that "greener pasture" that the best and the brightest gravitate toward. PMID- 1292857 TI - [Effect of interleukins and somatomedins on the production of neurotensin by cell line SH-SY5Y derived from human neuroblastoma]. AB - The goal of this study was to investigate the regulation by insulin-like growth factors 1 and 2, and interleukins on the production of neurotensin in the SH-SY5Y cell line derived from a human neuroblastoma. Cultures were performed in RPMI1640 culture medium with heated foetal calf serum 12%. After 24 hrs. of fasting without serum, interleukins-1 alpha, IL-2, IL-4 and insulin-like growth factors 1 and 2 were added. Results showed: 1) A mitogenic effect of ILs (p < 0.001) and of IGFs (p < 0.001). 2) The presence of neurotensin in HCl0.1N cellular extracts (0.06 fmol/micrograms protein). 3) The increase of cellular neurotensin content in the presence of IL-4 (560%), IL-2 (480%), IGF-1 (610%) and IGF-2 (200%). Our results indicate that the human neuroblastoma cell line SH-SY5Y produces neurotensin and that ILs and IGFs act in vitro to modulate this production. PMID- 1292859 TI - Dentists at risk: an interview with Dr. Bob Brandon. PMID- 1292860 TI - Stress factors and coping strategies in the dental profession. AB - Stress is inherent in dental practice. Identifying stressful factors is the first step toward coping with the insidious nature of stress, as preventive measures can then be efficiently established. While numerous studies have been conducted, none of them has identified a specific stress factor that is common to all practitioners, which demonstrates the multifactorial and multidimensional aspects of dental stress. PMID- 1292861 TI - Dental care for the psychiatric patient: chronic schizophrenia. AB - In recent years, there has been a shift in philosophy concerning the overall delivery of mental health services. As a result, the treatment and management of patients with various psychiatric and behavioral disorders have undergone some fundamental changes. Improved diagnostic and treatment modalities have, in many instances, reduced the need for long-term institutionalization for a large number of these patients. Consequently, community-based mental health agencies (e.g., group homes, homes for special care patients, etc.) are now assuming an increasingly important role in the long-term management of these patients, providing, for example, more sophisticated mental health promotion programs and counselling services. A greater positive interaction now exists between these individuals and the surrounding community, thereby encouraging a more favorable integration within society as a whole. Due to this shift from primarily an institutional-based treatment regimen to a more community-oriented approach, the general dental practitioner can expect to see and be requested to treat an increasing number of these patients, many of whom present with significant dental pathology. The purpose of this paper will be to provide an overview of the oral health findings and management protocols for those individuals suffering from one specific form of psychiatric illness--chronic schizophrenia. An attempt will be made to familiarize the practising dentist with the main psychopathological features of this disorder as well as the specific oral health care requirements and management protocols for these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292862 TI - Comparison of dental caries and oral hygiene indices for 13- to 14-year-old Quebec children between 1977 and 1989-1990. AB - A comparison of the principal dental health indices of 13- to 14-year-old Quebec school children between 1977 and 1989-1990 is reported. Data derive from a dental health survey of 1,093 Quebec school children in 1977 and from a province-wide probability sample of 1,342 children in 1989-1990. The most interesting conclusions are: the DMFT index for 13- to 14-year-old children dropped from 9.0 to 4.5; an improvement in the caries treatment level from 26 per cent to 90 per cent is noted; caries treatment needs decreased from 55 per cent to nine per cent; the mean number of extracted teeth per child dropped from a score of 1.6 to a score of 0.03; significant differences in the DMFT index between residential status no longer exist; and no improvement in the oral hygiene condition (OHIS index) is observed. In 1989-1990, 35 per cent of these adolescents had perfect periodontal health. For the others, the principal problems were bleeding gums and/or calculus. PMID- 1292863 TI - [Special considerations relating to class 1 and class 2 removable partial dentures in the mandible]. AB - During the rehabilitation of partially edentulous patients, dentists must try to preserve the health of the remaining oral structures. That is why it is essential to make maximum use of the support areas. With removable class 1 and 2 prostheses (Kennedy-Applegate classification), the remaining teeth and the edentulous areas provide support. While virtually no movement from the teeth is noticeable, the tissues covering the edentulous ridges do move in a variable manner. A unit must therefore be designed and built to protect the remaining teeth as well as the residual ridges. The problem is all the more acute for the mandible, since the compressibility of the tissues of the edentulous ridges and remodeling of the bone are greater. Many approaches and techniques have been described in the dental literature: functional impressions, use of appropriate direct retainers, and relining of units, if necessary. PMID- 1292864 TI - [The short- and long-term results in heart surgery of the elderly]. AB - We have studied retrospectively 106 patients aged 69 years or older (range 69 to 79) who underwent cardiac surgery between November 1986 and December 1989. The majority of patients (61%) were male. Coronary artery bypass surgery was performed in 59 patients, isolated valve replacement in 38 and combined valve replacement with coronary artery bypass surgery in 5. Two patients underwent ascending aorta replacement for aortic dissection and 2 ventricular aneurysmectomy and postinfarction ventricular septal defect repair. The mean postoperative hospital stay was 12 days. Ninety-one percent of patients underwent a primary elective operation and 9% required an emergency operation. Hospital mortality was 5% (n = 6). All hospital survivors were followed up by telephone contact (mean follow-up: 37 months) to determine presence or absence of chest pain, dyspnea, postoperative NYHA class and the overall effect of surgery on quality of life. There were 16 follow-up deaths; 5 were non cardiac. Follow-up study showed significant improvement in symptom status and quality of life (96%). We concluded that cardiac surgery in the elderly, although associated with increased operative risk, gives excellent relief of symptoms and good survival. PMID- 1292865 TI - [The determination of myocardial necrosis in unstable angina by the immunoradiometric measurement of circulating myosin]. AB - Ventricular myosin heavy chains serum levels are a new marker of myocardial necrosis. We have studied plasma levels of myosin in 30 patients with unstable angina, 30 patients with acute myocardial infarction and 25 healthy subjects. The myosin peak level was 317 +/- 101 microU/L in angina patients, 2510 +/- 433 microU/L in infarcted patients and 62.3 +/- 17 microU/L in the controls. In both groups, the increase in serum myosin was more marked in those with larger infarction and in those with more severe angina. These data suggest that the measurement of serum myosin can identify the presence of micronecrosis in patients with unstable angina, according to what has been found using other markers of myocellular necrosis. PMID- 1292866 TI - [The emergency treatment of supraventricular tachyarrhythmias: the efficacy and safety of intravenous propafenone]. AB - One hundred patients, admitted to the Emergency Unit for paroxysmal supraventricular tachycardia (SVT) with 1:1 AV conduction, atrial fibrillation (af) and flutter (AF) of recent onset (less than 72 hours) were treated with intravenous propafenone (P). The drug was administered at the dose of 70 mg over 5 min, repeated after 10 min if sinus rhythm (SR) was not restored and eventually followed by continuous infusion (0.35-0.50 mg/min) until conversion to SR or during the next 48 hours. Exclusion criteria were ventricular rate < 100/min, R-R intervals > 1 s, clinical signs of heart failure or asthma. Termination of SVT within 30 min was obtained in 94% of the patients, while reversion to SR occurred in 79% with af and in 55% with AF. For af and AF conversion was achieved within 30 min in 49% of overall responders (R), between 30 min and 6 hours in 27% and between 6 hours and 48 hours in 24%. The efficacy of P was significantly influenced by the duration of arrhythmia and left atrial size, measured by 2D echocardiography. On the contrary, no difference was observed between R and non-R in mean age and in the percentage of primary or relapsing arrhythmias. Adverse effects were encountered in 7 patients: in 1 case worsened arrhythmia and in 6 patients, with long-lasting arrhythmias, congestive heart failure. Neither conduction disturbance nor extra-cardiac complications occurred. In conclusion, P provides effective and safe treatment for paroxysmal atrial tachyarrhythmias, so that it can be considered among the drugs of first choice even in non-intensive care units. PMID- 1292867 TI - [Recurrent cardiac echinococcosis: a report of a case with multiple intrapericardial cysts]. AB - A case of an isolated recurrent cardiac hydatidosis with multiple intrapericardial cysts is presented. The patient, who underwent 2 previous surgical resection of intramyocardial and pericardial hydatid cysts, presented with atypical chest pain. The ECG and the perfusion scintigraphy with 201 thallium showed a previous lateral myocardial infarction. The diagnosis of recurrent cardiac hydatidosis was made by two-dimensional echocardiography and computed tomography and was confirmed by clinical and biochemical findings. PMID- 1292868 TI - [The correlation between the acidic composition of diacylglycerol and protein kinase C activation in cultures of rat cardiomyocytes]. AB - We have studied the fatty acid composition of the diacylglycerol produced after different stimulation times with an alpha 1-agonist (phenylephrine) in cultures of beating neonatal rat cardiomyocytes, and we have related the acidic pattern to the time course of the translocation of protein kinase C from cytosol to the membrane, both in control cells and in cells grown in a medium supplemented with docosahexaenoic acid. Gas chromatography of the diacylglycerol produced after stimulation revealed significant differences between control cells and cells grown in the docosahexaenoic acid supplemented medium. In the control cells, in the early stimulation times, the higher protein kinase C activity was due to a higher relative molar content of arachidonic acid in the diacylglycerol; in the docosahexaenoic acid treated cells the lower but more persistent activation of the membrane-bound protein kinase C might be sustained by an enrichment of diacylglycerol with docosahexaenoic acid. The modification of the fatty acid composition of diacylglycerol can cause an alteration in the response of the cells to alpha 1-adrenoceptor stimulation. PMID- 1292869 TI - [The inotropic and bathmotropic effects of beta stimulation: a study comparing dobutamine and dopamine on the guinea-pig papillary muscle in isotonic contraction]. AB - The study was aimed at comparing the effects of dobutamine (dob) and dopamine (dop) on isotonic contraction and rhythmicity of isolated guinea-pig papillary muscles (in oxygenated Tyrode at 37 degrees C), by taking into account: 1) the rate of stimulation (50% above the diastolic threshold) at 5 fixed periods: (RR: 1600, 1200, 1000, 800 and 400 ms); 2) 7 log concentrations (logC) of the index amine (from 10(-9) to 10(-3) M). To this end, a dose-relation protocol which explored the effects of all 5 RR and 7 logC was designed and 15 adult female Guinea-pigs (250 to 350 g) were randomized to either the dob (n = 8) or the dop (n = 7) arm. This enabled a total of 525 sets of data to be analyzed: in 38 sets (7.2%) premature contractions (CP) were coded. CP were sustained (freq: > 3) in 25 of these latter 38 sets (4.8%). Compared to the basal state, the amplitude (AMP%) and the log of percent amplitude (logAMP%) and time to peak (TP%) changes of the isotonic (Gould transducer) twitch were calculated along with the log of this latter variable (logTP%). AMP%, log AMP%, TP% and logTP% were linearly correlated with logC at all RR. In the range 1600-400 RR, for both amines, significant linear correlations (magnitude of 0.15 > r < magnitude of 0.70, 0.001 > p < 0.022) were seen for plots of AMP%, logAMP% and TP%:steeper correlations were observed for dop. This was confirmed in multivariate analysis (BMDP-9R) whereby AMP%, logAMP%, TP%, logTP%, CP, and freqCP were dependent variables and coded variables were included to either define the type of treatment (dop versus dob) or logC. In these analyses, logC (t > 11) and dop (t > magnitude of 3) might be used to explain (0.28 > r2 < 0.42, 0.00001 > p < 0.0025) AMP% and logAMP%, meaning that a different inotropic (isotonic) efficacy exists between these 2 amines, at all logC. On the other hand, when CP and freqCP were coded, explanatory variables were AMP% and logAMP% (4.86 > t < 6.95, 0.06 > r2 < 0.09, p < 0.00001), but not the variable used to code the type of treatment (dob versus dop).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1292870 TI - [A 31P-NMR spectroscopic study of the changes in energy metabolism induced by cardiac ischemia and reperfusion in rats of different ages]. AB - In order to investigate the energetic status of the aged heart during ischemia and reperfusion we perfused female Wistar rats 6, 12 and 24 month old. The hearts were subjected to 15 min of global total ischemia plus 30 min of reperfusion. NMR spectra were collected during the entire experimental period to have the in vivo monitoring of the changes in intracellular pH and intracellular ATP, PCr and Pi contents. In the first 8 min of ischemia the fall of pH was similar in the 3 groups of rats, while at the end of the ischemic period the young rat hearts showed an intracellular pH significantly lower than aged rat hearts. At the end of reperfusion, ATP and PCr contents appeared significantly higher in the adult and aged hearts as compared to the young. The Pi content, on the contrary, was significantly lower in aged than young rat hearts. We suggest that the hearts of adult and aged animals, at the end of reperfusion, showed larger energetic recovery, in our experimental conditions of brief ischemia, than young hearts. PMID- 1292871 TI - [Ischemia and reperfusion: the production and release of malondialdehyde, oxypurines and nucleosides in the isolated rat heart]. AB - Ischemia and reperfusion damage has been evaluated by determining the sum of adenine nucleotides, nucleosides, oxypurines and the concentration of malondialdehyde, ascorbic acid, lactate and pyruvate in the isolated rat heart subjected to global normothermic ischemia and subsequent reperfusion. In addition, the sum of oxypurines and nucleosides, and the concentration of malondialdehyde has been determined in the perfusate collected during the reperfusion. Data indicate that ischemia and reperfusion induce an oxidative stress to myocardial tissue (increase of tissue malondialdehyde and decrease of ascorbic acid, and release of malondialdehyde during reperfusion) that, due to the output of relevant amount of oxypurines (congruent to 6.7 mumol/g dry weight) and of nucleosides (congruent to 7.0 mumol/30/min/g dry weight), it is not even able to restore its energy metabolism after reperfusion. PMID- 1292872 TI - [The effects due to reduced coronary inflow and hypoxemia during myocardial ischemia]. AB - The events associated to myocardial ischemia result from 2 overlapping phenomena due to reduced blood flow (ischemia) and reduced O2 supply (hypoxemia). To distinguish these effects, 2 groups of isolated rat hearts were perfused through the aorta (Langendorff's method) with Krebs-Henseleit buffer, and were exposed for 20 min to hypoxemia or ischemia, matched in terms of the O2 supply (10% of baseline), with continuous monitoring of cardiac contractility, O2 uptake and lactate production. The developed pressure and the O2 uptake were similar in hypoxemic and ischemic hearts; heart rate, end-diastolic pressure and lactate production rate were higher in hypoxemia than in ischemia; the recovery from hypoxemia was less than that from ischemia, despite the same O2 supplies; treatment with superoxide dismutase and catalase, scavengers of the O2 derived free radicals, during hypoxemia, allowed hypoxemic hearts to recover as ischemic hearts. Therefore, the main determinant of the reperfusion injury is to be attributed to the low O2 supply rather than to the low coronary flow; part of the injury is due to free radicals; a substantial portion is mediated by the energy demand during the stress which was higher in hypoxemia than in ischemia. PMID- 1292873 TI - [The enzymatic activity of adenosine metabolism in the rat heart. The effects of cardiac hypertrophy]. AB - The transmural distribution of the adenosine metabolizing enzyme activities 5'nucleotidase (5'N) and adenosine deaminase (ADA) across the left ventricular wall was explored in rats with heart hypertrophy induced by aortocaval shunt (FAC), or coarctation of the abdominal aorta (S) or by tireotoxicosis (T). FAC caused largest heart hypertrophy with a very short latency (1 day: + 0%, 3.5 days: + 30%, 7 days: + 41%, 21 days: + 49%). A 30% increase in the left ventricle free wall was observed after 3.5, 14 or 28 days of treatment with FAC, T or S respectively. Different changes in enzyme levels and alteration of transmural distribution profiles were observed with the different types of heart hypertrophy. Level of 5'N was decreased with FAC, did not change with T and increased with S; levels of ADA were always increased. The pattern of the transmural distribution of 5'N was affected by S but not by T and FAC, whereas distribution of ADA was not affected by S and T and was altered by FAC transiently. PMID- 1292874 TI - [Isoproterenol causes changes in the mitochondrial energy metabolism in the rat heart]. AB - In this paper we report observations on kinetic and structural characteristics of mitochondrial ATP synthase of rat-heart after subcutaneous injection of isoproterenol. The results obtained indicate: a decrease of respiratory rate either in absence (state 4) or in presence (state 3) of oxidative phosphorylation; decrease of respiratory control ratio; decrease of ATP hydrolase activity in sonic submitochondrial particles; decrease of relative content of the catalytic subunit F1 with respect to the membrane sector F0. The data obtained are in favour of the hypothesis that isoproterenol causes structural and functional alterations of mitochondrial ATP synthase. PMID- 1292875 TI - Expression of desmin cDNA in PtK2 cells results in assembly of desmin filaments from multiple sites throughout the cytoplasm. AB - The assembly of intermediate filaments into a cytoplasmic network was studied by microinjecting into the nuclei and cytoplasms of PtK2 cells, plasmids that contained a full length desmin cDNA and an RSV promoter. Immunofluorescence was used to monitor the expression of desmin and its integration into the cells' vimentin intermediate filament network. We found that the expressed desmin co localized with filaments of vimentin just as it does with fluorescently labelled desmin is microinjected into the cytoplasm of PtK2 cells. As early as two hours after microinjection of the plasmids, small discrete dots and short fragments of desmin could be detected throughout the cytoplasm of the cells. This initial distribution of desmin was superimposed on the filamentous pattern of vimentin in the cells. At 8 hours after microinjection of the plasmids, some of the desmin was present in long filaments that were coincident with vimentin filaments. By 18 hours, most of the desmin was in a filamentous network co-localizing with vimentin. There was no indication that desmin assembly began in the perinuclear region and proceeded toward the cell periphery. In some cells, excessively high levels of desmin were expressed. In these cases, overexpression led to clumping of desmin filaments as well as to an accumulation of diffusely distributed desmin protein in the center of the cells. This effect was apparent at approximately 18 hours after introduction of the plasmid. The native vimentin filaments in such cells were also aggregated around the nucleus, co-localizing with desmin. The microtubule networks in all injected cells appeared normal; microtubules were extended in typical arrays out to the periphery of the cells. PMID- 1292876 TI - Desmosome assembly in MDCK epithelial cells does not require the presence of functional microtubules. AB - Desmosomes, complex multisubunit structures that assemble at sites of cell-cell contact, are important components of the epithelial junctional complex. Desmosome assembly requires the coordinated interaction at the plasma membrane of at least 8 cytoplasmic and integral membrane proteins organized into two structurally and functionally distinct domains, the cytoplasmic plaque and membrane core. Previous studies (Pasdar et al., J. Cell Biol., 113:645-655) provided evidence that cytokeratin filaments and microtubules may regulate transfer and assembly of cytoplasmic plaque and membrane core proteins, respectively. To determine directly the role of microtubules in these processes, Madin-Darby canine kidney (MDCK) cells were treated with nocodazole or colchicine to disrupt the microtubular network. Biochemical analysis of the different components of the cytoplasmic plaque and membrane core domains revealed little or no effect of nocodazole or colchicine on the kinetics of synthesis, post-translational modifications, transfer of proteins to the plasma membrane or their metabolic stability in the presence or absence of cell-cell contact. Likewise, immunofluorescence analysis of desmosome formation demonstrated an apparently normal desmosome assembly in the presence of nocodazole or colchicine upon induction of cell-cell contact. These results indicate that an intact microtubular network is not necessary for the processing or transport of the desmosomal membrane core glycoproteins to the plasma membrane in the absence or presence of cell-cell contact. Furthermore, the integration of the cytoplasmic plaque and membrane core domains induced by cell-cell contact at the plasma membranes of adjacent cells does not require the presence of functional microtubules. PMID- 1292877 TI - LC20 and kinetics of gizzard myosin subfragment-1: digestion with papain vs. S. aureus protease. AB - Previous reports have shown that papain-digested gizzard subfragment-1 (PAP-S1) has a cleaved regulatory light chain (LC20), and Vmax similar to phosphorylated heavy meromyosin (HMM) (Greene et al., Biochemistry 22:530-535, 1983; Sellers et al., J. Biol. Chem. 257:13880-13883, 1982; Umemoto et al., J. Biol. Chem. 264:1431-1436, 1989], while S. aureus protease-digested S-1 (SAP-S1) has intact LC20, but Vmax closer to that of unphosphorylated HMM [Ikebe and Hartshorne, 1985]. To determine whether intact LC20 inhibits ATPase activity for subfragment 1 (S1), we compared the kinetic properties and structures of unphosphorylated PAP S1 and SAP-S1. SDS-PAGE showed that SAP-S1 had 68 and 24 KDa heavy chain and 20 and 17 KDa light chain components. PAP-S1 (15 minutes digestion at 20 degrees C) also had 68 and 17 KDa bands, but the single 24 KDa band (24HC) was replaced by a group of 22-24 KDa fragments and LC20 was cleaved to a 16 KDa fragment. At 13 mM ionic strength, both PAP-S1 and SAP-S1 had Vmax similar to phosphorylated HMM (1.1-1.5 s-1). SAP-S1 had the same KATPase as phosphorylated HMM (38 microM actin), but KATPase for PAP-S1 was 3-fold stronger (11 microM actin). Subsequent digestion of SAP-S1 with papain did not significantly change Vmax, but as LC20 and 24HC were cleaved, both KATPase and Kbinding strengthened 3- to 5-fold. Thus, intact LC20 did not inhibit, and cleavage of LC20 did not increase Vmax for S1. Rather, papain cleavage of LC20 and 24HC was associated with strengthened actin binding. PMID- 1292878 TI - Tubulin dimer formation via the release of alpha- and beta-tubulin monomers from multimolecular complexes. AB - The functional subunit of microtubules is a heterodimer consisting of alpha- and beta-tubulin. An understanding of tubulin dimerization has been hampered because it has not proved possible to purify native tubulin monomers. To study the process whereby tubulin dimers are formed, we made use of tubulins synthesized by in vitro transcription and translation. We present evidence that the in vitro synthesis of different mouse alpha-tubulin isotypes involves a multimolecular complex. The synthesis of mouse beta-tubulin isotypes also involves the formation of multimolecular complexes, though different isotypes behave somewhat differently from one another. The properties of in vitro synthesized alpha- and beta-tubulin multimolecular complexes strongly suggest that they are intermediates in the biosynthesis of tubulin monomers. Upon release, these monomers can exchange with pre-existing tubulin heterodimers. PMID- 1292879 TI - The effect of hemorrhagic shock on intestinal amino acid absorption in vivo. AB - Hemorrhagic shock causes a disproportionate decrease in portal blood flow which may adversely affect the barrier and absorptive functions of the intestine. The absorptive capacity of the small intestine was studied during shock induced by mild and severe hemorrhage in the rat by measurement of the uptake of a radiolabelled amino acid analog (aminoisobutyric acid: AIB). Hemorrhage resulted in a significant reduction in systemic blood pressure, portal blood flow, and the absorption of AIB from the small intestine. Resuscitation restored both blood pressure and portal blood flow. But a significant reduction in absorption of AIB persisted. This suggests that hemorrhage results in an inhibition of amino acid intestinal active transport which is not dependent on the mesenteric circulation. The reduced intestinal absorptive function has important implications for the route of administration of nutrition following hemorrhage and trauma. PMID- 1292880 TI - Arterial norepinephrine changes in patients with septic shock. AB - Arterial, mixed venous (pulmonary arterial), and peripheral venous norepinephrine and epinephrine levels; hemodynamics; and blood lactate levels were measured in 28 patients with septic shock (16 men and 12 women). During hospital follow-up, 18 patients (64%) died of circulatory failure. There were no significant differences in hemodynamic parameters or initial blood lactate levels between survivors and nonsurvivors. Initial arterial, mixed venous, and peripheral venous norepinephrine levels were elevated above normal in both survivors and nonsurvivors. However, norepinephrine levels at all three sampling sites were significantly higher in nonsurvivors than in survivors. Arterial or mixed venous norepinephrine level was better than peripheral venous norepinephrine level in distinguishing survivors from nonsurvivors. In contrast, the differences in plasma epinephrine levels between survivors and nonsurvivors became significantly different only after 48 hr of follow-up. During 60 degrees head-up tilt, the increase in plasma norepinephrine level was significantly higher in survivors compared to non-survivors, suggesting a differential response in the sympathetic nervous system in the two groups of patients. These data suggest that measurement of arterial or mixed venous plasma norepinephrine levels may be a useful guide for assessing the clinical course of patients in septic shock. Moreover, the differences in the sympathetic nervous system response to a 60 degree tilt may predict a poor outcome in these patients. PMID- 1292881 TI - In vitro plasma perfusion through adsorbents and plasma ultrafiltration to remove endotoxin and cytokines. AB - In vitro plasma perfusion experiments were performed using small columns containing either resin or charcoal adsorbents to assess the removal of cytokines and endotoxin. 125I-labelled tumor necrosis factor-alpha (TNF-alpha; 500 pg/ml) and interleukin-6 (IL-6; 10 ng/ml) were added individually to human plasma. Over 4 hr of perfusion, Amberlite XAD-7 resin removed 32.5% +/- 3.3% (n = 5) of the initial amount of TNF-alpha and 71.4% +/- 3.8% (n = 5) of the initial amount of IL-6. DHP-1 polyhema-coated activated charcoal removed 17.2% +/- 6.2% (n = 5) of TNF-alpha and 48.5% +/- 7.4% (n = 5) of IL-6. Preliminary experiments were performed with lipopolysaccharide (LPS; 100 ng/ml) and interleukin-1 alpha (IL-1 alpha; 500 pg/ml), which showed that, over 4 hr, Amberlite XAD-7 removed 10.3% of the initial LPS and 29.1% of IL-1 alpha, whereas DHP-1 charcoal removed 23.2% of the initial LPS and 65.3% of IL-1 alpha. In vitro plasma ultrafiltration with either polysulfone or polyacrylonitrile membranes, as used clinically in haemodialysis, was performed with recirculation of plasma containing LPS or TNF alpha. Neither of the substances was filtered to a significant degree. In conclusion, direct removal of these inflammatory mediators from the circulation of patients with multiorgan failure due to fulminant hepatic failure or sepsis would be possible by perfusion of plasma through adsorbents but not by haemodialysis. PMID- 1292882 TI - Lung innervation and the hemodynamic response to 7% sodium chloride in hypovolemic dogs. AB - A pulmonary vagal reflex triggered by passage of hypertonic saline through the pulmonary circulation has been proposed as one of the mechanisms by which hypertonic saline resuscitates dogs in hemorrhagic shock. Thirteen anesthetized dogs with denervated left lung lobes were subjected to a standard hemorrhage model to evaluate this purported reflex. We then infused 7% NaCl (4 ml/kg) into either the innervated (six dogs) or the denervated (seven dogs) pulmonary circulation. There were no differences in cardiac output, mean arterial pressure, right atrial pressure, heart rate, or peripheral vascular resistance between groups during a 1 hr period after 7% NaCl infusion. Changes in hematocrit, total plasma protein, and osmolality after 7% NaCl administration suggested that plasma volume expansion had occurred and was similar between groups. We conclude that a pulmonary reflex elicited by hypertonic saline does not contribute to the beneficial hemodynamic effects associated with administration of 7% NaCl during hemorrhagic shock. PMID- 1292883 TI - Effects of continuous naloxone infusion in intestinal ischemia shock in the rat. AB - The effects of continuous naloxone infusion on the response to intestinal ischemia-reperfusion were studied in a rat model. Naloxone was given as a bolus injection (2 mg/kg bw) followed by a continuous infusion (4 mg/kg bw/h) starting before (-10 min) intestinal ischemia was applied (0-60 min) and continuing 2 h after reperfusion of the intestine. Blood pressure, acidosis and survival were determined. Saline-infused shocked rats and untreated shocked rats served as comparisons and non-shocked animals as controls. Blood pressure was slightly higher before and during the continuous naloxone infusion but did not differ after reperfusion in the three shock groups. Acidosis was less pronounced in naloxone compared to untreated shocked rats. Survival rates were significantly higher in naloxone-treated shocked rats compared to untreated shock and significantly lower in saline treated shocked rats compared to non-shocked controls. In conclusion a naloxone effect on acidosis and survival in shock after intestinal ischemia and reperfusion is possible. PMID- 1292884 TI - Tolerance of the liver as measured by ketone body ratio and hepatocyte energy charge to 120 minutes acute venous congestion in dogs. AB - Although acute passive hepatic congestion (APHC) sometimes occurs in patients undergoing open heart surgery or liver transplantation, the effects and safety limits of APHC on hepatic energy status have yet to be investigated. The present study reports an APHC model in 11 dogs in comparison with a control in 9 dogs by clamping the throacic inferior vena cava with passive venovenous shunt (APHC group) and by clamping the same with an active shunt at a rate of 60 ml/min/kg (control group). We investigated the effects of 120-min APHC on hepatic energy status by assessing the changes in arterial ketone body ratio (KBR) and hepatic energy charge (EC). After induction of the APHC, portal vein pressure elevated significantly to almost three times the control level. KBR decreased significantly for 60 min as compared with that of the control, but gradually recovered thereafter, returning to the preclamping level after reversal. Although total hepatic blood flow after 60-min clamping was approximately 18% of the preclamping value, no significant differences in EC and KBR values were seen after 60-min clamping as compared with preclamping and the control. All dogs in both groups survived at least 1 week. In this experimental model, 120-min APHC had no long-term effects on hemodynamics and energy production in the liver. PMID- 1292885 TI - Antishock and endothelial protective actions of a NO donor in mesenteric ischemia and reperfusion. AB - Splanchnic artery occlusion (SAO) of the celiac, superior mesenteric, and inferior mesenteric arteries for 2 hr, followed by a 2-hr reperfusion period in cats produces a severe form of circulatory shock characterized by endothelial dysfunction, increased lysosomal leakage, and severe hypotension resulting from release of proteases, oxygen-derived free radicals, and other humoral mediators into the circulation. Administration of 0.75 mg/kg/hr of C873754, a nitric oxide (NO) donor, 10 min prior to reperfusion, significantly attenuated the accumulation of plasma cathepsin D from 12 +/- 3 U/ml in the SAO + vehicle group to 5 +/- 1 U/ml (P < 0.05) in the C87-3754 treated SAO group. A similar attenuation of plasma myocardial depressant factor (MDF) activity was observed in the C87-3754 treated cats (P < 0.02). Administration of C87-3754 significantly increased short term (i.e., 2-hr) survival rate (P < 0.05, compared to the vehicle group). Moreover, C87-3754 attenuated the SAO shock induced decline in release of endothelium-derived relaxing factor (EDRF) from isolated superior mesenteric artery (SMA) rings stimulated by acetylcholine and A23187. Additionally, C87-3754 significantly decreased PMN adherence to the superior mesenteric venous endothelium in vitro. Thus, treatment with the NO donor, C87 3754 reduced the accumulation of humoral mediators into the plasma while significantly attenuating endothelial dysfunction and improving short term survival. PMID- 1292886 TI - Septic focus localized by determination of arterio-venous difference in neopterin blood levels. AB - We describe a case of a 38-year-old female accident victim who was admitted to the trauma hospital with an ISS of 66. Successful emergency treatment (including amputation of the left leg) and 4 weeks of intensive care led to an overall improvement so that the patient was extubated on day 29. Throughout this period neopterin was measured routinely 3 times a week and correlated well with the clinical course. At the end of the fifth week massive lung impairment and all clinical signs of sepsis appeared. Neopterin values increased dramatically up to 200 nmol/L. However, no abnormal findings were revealed by X-ray, contrast fluoroscopy, or sonographic imaging. To examine the amputation site more closely, simultaneous determination of neopterin in samples from the vena and arteria femoralis was performed. We found a 50% higher level in the venous blood (300 vs. 200 nmol/L). This was regarded as evidence for a hidden focus. Immediate surgical intervention revealed an abscess, which proved to be Pseudomonas aeruginosa positive. After adequate treatment the patient recovered quickly. In this case neopterin was not only helpful in monitoring the septic episodes of the patient, but proved essential for the detection of a septic focus and the risk of explorative relaparotomy could be omitted. PMID- 1292888 TI - Comparison of the pulmonary lymphatic and hemodynamic changes of near-drowning in a sheep model. AB - The hemodynamic and lung lymph changes following near-drowning (ND) were studied in sheep. Experimental ND was by transtracheal aspiration of 10 ml/kg body weight of either seawater (SW) or freshwater (FW). Extravascular lung water and lung lymph protein flux were significantly increased, but cardiac index was depressed in both groups following ND. Systemic and pulmonary vascular resistances were markedly elevated with FW compared to only a slight rise with SW. Lung lymph oncotic pressure decreased with SW ND from baseline of 9.7 +/- 0.4 to 6.8 +/- 0.63 mm Hg (P < 0.05). In contrast, FW ND increased lung lymph oncotic pressure from 12.8 +/- 0.9 to 16.6 +/- 1.3 mm Hg (P < 0.05). These data suggest that the changes in lung lymph and hemodynamic response to SW and FW ND differ in sheep. The changes are immediate and profound with SW, but slower in onset and less severe with FW. FW ND is associated with hemolysis, which is absent in SW ND. PMID- 1292887 TI - Calcium transport by rat liver plasma membranes during sepsis. AB - The effects of sepsis on the ATP-dependent Ca2+ transport in rat liver plasma membranes were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. The results show that the ATP-dependent Ca2+ transport by liver plasma membranes was not affected during early sepsis (9 hr after CLP) but was decreased by 30-50% (P < 0.05) during late sepsis (18 hr after CLP). Kinetic analysis of the data indicates that during late sepsis, the Vmax values for ATP and for Ca2+ were decreased by 38.5% (P < 0.05) and 41.8% (P < 0.05), respectively, while the Km values for ATP and Ca2+ remained unchanged. Mg2+ stimulated ATP-dependent Ca2+ transport. The Mg(2+)-stimulated activity was unaffected during early sepsis but was decreased by 34-63% (P < 0.05) during late sepsis. These data demonstrate that ATP-dependent Ca2+ transport in rat liver plasma membranes was impaired during late sepsis and that the impairment is associated with a mechanism not affecting the affinity of the Ca2+ transporter for ATP and Ca2+. Since plasma membrane ATP-dependent Ca2+ transport plays an important role in the regulation of intracellular Ca2+ homeostasis in hepatocytes, an impairment in the ATP-dependent Ca2+ transport by liver plasma membranes during late sepsis may have a pathophysiological significance in contributing to the development of altered hepatic metabolism during septic shock. PMID- 1292889 TI - Hyperdynamic sepsis in baboons: II. Relation of organ damage to severity of sepsis evaluated by a newly developed morphological scoring system. AB - The purpose of our study was to set up a baboon hyperdynamic sepsis model with live bacteria administration, which produces within 8 hr an organ failure comparable to human pathological conditions. Twelve adult male baboons were instrumented and studied for 8 hr under pentobarbital (2-3 mg/kg BW/hr) anesthesia breathing spontaneously. The animals were divided into two groups: 1) Live Escherichia coli were infused intravenously at a dose of 1.0-2.0 x 10(10) CFU/kg BW over 8 hr; 2) Live E. coli were infused i.v. at a dose of 5 x 10(8) CFU/kg BW over 2 hr. Organ damage was monitored by a newly developed scoring system. Organ damage was clearly dependent on the concentration of the bacterial challenge. Bacterial challenge at a dosage of 5.0 x 10(8) produces insignificant hemodynamic effects, while the 1.0-2.0 x 10(10) animals demonstrated massive hemodynamic alterations and needed much higher fluid support. The higher E. coli dosage was associated with an overwhelming organ damage seen, e.g., from the lung weight (12 g/kg BW vs. 9.6 g/kg BW with the lower dosage) or from the organ failure score, which is based on macroscopic pathology, histological data and organ weight. The percentage of animals with one, two, or three organ failures (organ failure score > or = 2) was higher in baboons with the higher dosage/kg BW. Therefore, we believe that the less severe organ damage in the acute phase after 8 hr with live bacteria 5 x 10(8) CFU/kg BW infusion over 2 hr is better to monitor the efficacy of newly developed therapeutic regimens, since in another set of experiments this model still produces lethal organ damage (80%) in a subchronic setting over 72 hr. PMID- 1292890 TI - Two types of septic shock classified by the plasma levels of cytokines and endotoxin. AB - We investigated plasma levels of cytokines and endotoxin in septic shock to clarify the roles of various cytokines in this type of shock. Endotoxemia was observed in 16 of 22 septic shock patients. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) IL-2, and IL-6 were significantly higher in septic shock than in sepsis without shock. Strong correlations were noted between TNF-alpha and IL-2 levels and between IL-1 beta and IL-6 levels. Patients with high TNF-alpha and IL-2 levels also showed endotoxemia. We defined two types of septic shock from these data, i.e., endotoxin+TNF-alpha + IL-2 shock and IL-beta + IL-6 shock. In the former type, high TNF-alpha and IL-2 levels were present before the onset of shock, and shock itself was associated with endotoxemia. The second type showed simultaneous elevation of IL-1 beta and IL-6 levels at the onset of septic shock, and endotoxin was detected in some of them. These results suggest that endotoxin and extremely high levels of TNF-alpha and IL-2, or the simultaneous elevation of IL 1 beta and IL-6, are related to the onset of septic shock. PMID- 1292891 TI - The genetic program for preimplantation development. AB - This review summarizes information on accumulation profiles of individual gene transcripts in preimplantation development. Most of the information is from the mouse, but some data from other species are reviewed as well. The principal finding is that the transcription of most genes is not temporally linked with any of the three morphogenetic transitions (compaction, cavitation, and blastocoel expansion) that characterize this period. Most genes that are expressed during preimplantation development of the mouse are already being transcribed in the 4 cell stage, and some clearly begin as early as the 2-cell stage. Once activated, a gene continues to be transcribed at least into the blastocyst stage, resulting in continuous mRNA accumulation. Thus the pattern of gene transcription established at the time of genomic activation in the 2-cell stage is perpetuated into the blastocyst, with a few additions along the way. This information is interpreted in light of previous findings concerning the sensitivity of morphogenetic transitions to inhibition of gene expression. The lack of a clear relationship between the timing of expression of most genes and the schedule of morphogenesis leads one to conclude that temporal regulation is imposed downstream of transcription and translation. This conclusion is substantiated by a consideration of factors controlling the events of compaction. PMID- 1292893 TI - Use of a yeast site-specific recombinase to generate embryonic mosaics in Drosophila. AB - An efficient method for generating embryonic mosaics using a yeast site-specific recombinase (FLP), under the control of a heat shock promoter, is described. FLP recombinase can promote mitotic exchange between homologous chromosomes that contain FRT (FLP Recombination Target) sequences. To demonstrate the efficiency of FLP-recombinase to generate embryonic mosaics, clones of the recessive and cell autonomous mutation armadillo (arm), detected by their ability to differentiate ectopic denticles in the naked cuticle of each abdominal segment, have been induced. We have analyzed the parameters of FLP-recombinase induced embryonic mitotic recombination and have demonstrated that clones can be efficiently induced during the postblastoderm mitotic divisions. We discuss applications of this technique for the analyses of the roles of various mutations during embryonic patterning. PMID- 1292892 TI - Sequence and expression of IMP-L1, an ecdysone-inducible gene expressed during Drosophila imaginal disc morphogenesis. AB - Drosophila imaginal discs are induced by the steroid hormone 20-hydroxyecdysone to initiate morphogenesis leading to formation of the adult appendages and thoracic epidermis at the end of the third larval instar. Ecdysone-dependent transcriptional activation of a set of genes that encode imaginal disc transcripts found on membrane-bound polysomes precedes and may be responsible for some aspects of the cellular changes that mediate epithelial morphogenesis in this system. A 1.35 kb transcript from one of these genes, IMP-L1, is first observed in vivo at or just prior to pupariation, as ecdysone titers are peaking and beginning to decline. Expression is initiated in proximal areas of the antennal disc, later spreading to a more widespread but nonuniform distribution throughout other thoracic imaginal discs. IMP-L1 is not, however, expressed in other ecdysone target tissues such as salivary glands or fat body. The IMP-L1 gene encodes a novel protein product containing a signal peptide, a possible transmembrane domain, two highly charged domains and a proline rich C-terminal domain. We suggest that the delayed timing of expression of this secondary response gene is necessary for proper ordering of cellular events associated with disc morphogenesis. PMID- 1292894 TI - [Evaluation of digital subtraction arthrography on the diagnosis of temporomandibular joint dysfunction syndrome]. AB - Digital subtraction arthrography of temporomandibular joint superior cavity (TMJSC-DSA) was performed for 70 cases with TMJ dysfunction syndrome. A comparative observation between the operative findings and the findings of TMJSC DSA examination was carried out for 11 cases who underwent TMJ operation. The results showed that TMJSC-DSA could overcome the disadvantages of conventional arthrography and make exact diagnoses for the anterior displacement of the disc and the disc perforation. PMID- 1292895 TI - [A study of the computer aid design for tooth arrangement of full denture]. AB - This paper is to use the power function Simpson's integration formula and some other methods to describe the geometric form of the dentition and edentulous arch in accordance with the theories and principles of tooth arrangement in textbook. The matching equations of artificial dentition and edentulous arch form and size are developed by using the multivariable regression method to analyze and summarize the clinical experiences of prosthodontists. Based on the above facts, a computer program that can be used to aid the dentist to arrange the artificial teeth for full denture is developed with Quick Basic Language and realized them in PC miniprocessors. PMID- 1292896 TI - [A method of cephalometric analysis]. AB - In this paper, 220 children ranging from age 11 to 15 were selected. Each of them received a cephalometric roentgenographic examination. 153 cephalometric items from 13 types of methods which had been widely in use were studied through statistic analysis. By means of "t" test, several items which expressed little difference between the normal occlusion and the malocclusion were eliminated. By using of the cluster analysis we selected one item to represent the items which were with similar effect. Finally, 17 cephalometric items were pick out to provide references for clinical work. PMID- 1292897 TI - [Experimental study of decalcified bone for transplantation]. PMID- 1292898 TI - [Cell morphometric analysis in oral submucous fibrosis, leukoplakia and squamous cell carcinoma]. AB - The morphometry of the cells and the nuclei in the spinous cells of oral epithelium in 48 specimens were studied by interactive image analysis system (IBAS-II). Five groups, normal mucosa, oral submucous fibrosis (OSF), leukoplakia, epithelial dysplasia and squamous cell carcinoma, were included. The result showed a progressive reduction in the dimensions (area, perimeter, all kinds of diameter) of the cells from normal mucosa, through OSF, leukoplakia, dysplasia to carcinoma (P < 0.01), while the dimensions of the nuclei did not show significant differences among the groups (P > 0.05), except the minimum diameter, but the nuclear cytoplasmic ratio showed a progressive increase (P < 0.01). The shape factors (form factor [PE] and contour index [CI]) seemed to be less helpful in identification. It indicated that the decrease of cell area of the spinous cell could reflect a malignant progress, and nuclear cytoplasmic ratio might be an objective feature to distinguish carcinoma from other lesions. The result also suggested that the pathological grade of OSF is between normal mucosa and mild epithelial dysplasia. PMID- 1292899 TI - [Clinical application of sclerosing agent injection in treating habitual dislocation of temporomandibular joint]. AB - Based on the experimental study, small amount of sclerosing agent was injected to the site outside the joint and below the ridge of TMJ on 105 cases for the treatment of habitual dislocation of TMJ. All of the cases were followed-up for more than 2 years and it was found that the cure rate reached 89 percent, including one case who was followed-up for 19 years free from recurrence. This method is suggested as it is simple to perform and acceptable to the patients. It has to be mentioned, however, that this injection was not so effective for those with cerebrovascular disease associated with habitual dislocation of TMJ. PMID- 1292901 TI - [Study on permanent magnet as a high-quality root-canal filling material]. PMID- 1292900 TI - [Research of women's periodontal conditions after using sex hormonal contraceptives]. PMID- 1292902 TI - [Comparison of facial nerve end-to-end suture and intramuscular implantation with facial muscle]. PMID- 1292903 TI - [Effects of Lycium barbarum L and Drynaria fortunei J Smith on in vitro attachment and growth of human gingival fibroblasts on root surfaces]. AB - In this study, the effects of Lycium barbarum L and Drynarna fortunei J Smith on in vitro attachment and growth of human gingival fibroblasts to root surfaces were investigated. The results revealed that the above herbs at dose of 1.25 mg/ml could improve attachment and growth of fibroblast, on the planed diseased root surfaces to a certain extent. When exposed to Lycium brabrum L cells on the diseased root surfaces increased markedly in number, with more even distribution, better spread, and more exuberant growth. Drynaria fortunei J Smith was not as potent as Lycium brabarum L. The results suggest that the two drugs may improve the formation of new attachment of periodontal tissue. PMID- 1292904 TI - [The effect on erythrocyte deformability in Sjogren's syndrome with treatment by activating blood and replenish body fluid]. PMID- 1292905 TI - [Analysis of two kinds of method in the treatment of mandibular fracture]. AB - In this paper, 27 cases of mandibular fracture with displaced fragment were divided into experiment group fixed by plate following AO principles and control group fixed by IMF. Through postoperative evaluation separately at the first, second, third month by means of X-ray, occlusal analysis based on dental models before and after fracture, occlusal force recording in areas of molar, premolar, incisors, and investigation of mandibular movement function during mastication, the results show that: (1) Occlusal relationship is not as satisfied as considered previously when IMF is used to treat mandibular fracture. In some cases, the dental cusps of molar and premolar don't contact tightly in lingual side, the occlusal plane seem to be inclined bucco-lingually. (2) The use of DC plate or EDC plate can avoid long-time IMF and reduce its complications, allow early function of mandibular fracture and follow the principles of biomechanics of combining mobility with static. As long as exact operative procedures, better occlusion than the use of IMF can be achieved. PMID- 1292906 TI - [Sagittal fracture of mandibular condyle (SFMC) of the children treated by occlusal pad]. AB - We have observed two cases of fresh SFMC of the children treated by occlusal pads and one case of old SFMC not treated. According to the survey of the above two kinds of SFMC, we conclude that: (1) The degree of the fractured fragment of the children are smaller than that in the adult. The outcomes of the cases treated by occlusal pads are good. (2) The condyle will be malformed and adhered to the lateral tubercle of the mandibular fossa in the untreated case. (3) The principles of the treatment of fresh SFMC are to prevent secondary trauma of the joint, to let the residual part of the condyle remodelling under light pressure and to reduce distance between the fractured fragments. The occlusal pad can fulfil these requirements. PMID- 1292907 TI - [A scanning electron microscopic study of surface layer changes in artificial carious enamel]. AB - The present study was carried out to describe surface changes and development of pathways of caries in vitro by the scanning electron microscope. Results indicate that direct crystal dissolutions of the surface layer itself are prominent features and recrystallization phenomenon is present in different degrees. The dissolution was more severe in Tome's process pit, focal hole and opening of striae of Retzius, but less severe in inter-rod areas. PMID- 1292908 TI - [Purification and characterization of a surface protein antigen from Streptococcus mutans]. PMID- 1292909 TI - [A preliminary report on the artificial blood vessel bridging of internal jugular vein for bilateral radical neck dissection]. PMID- 1292910 TI - [Photoocclusion analysis for the reduction of occlusal table dimension of the pontics]. AB - 50 cases of mandibular dentitions with normal morphology and occlusion are analyzed by using photoocclusion. The occlusal surfaces of the molars are divided into four regions buccolingually. That are the buccal inclines and lingual inclines of the buccal and lingual cusps of the molars. The relationship of sigma epsilon value among these four regions is 3:5:2:0 respectively. This indicates that it is effective to get force reduction by adjusting the buccal incline of the pontic in fixed bridge restoration. PMID- 1292911 TI - Animal models of non-insulin-dependent diabetes. PMID- 1292912 TI - Pancreatic beta cells in insulin-dependent diabetes. PMID- 1292913 TI - Insulin-like growth factors and diabetes. PMID- 1292914 TI - Bactericidal activity and postantibiotic effect of cefdinir (Cl 983, FK 482) against selected pathogens. AB - The bactericidal activity and the postantibiotic effect (PAE) of cefdinir (Cl 983, FK 482) (CDR), were determined against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis and Escherichia coli (5 strains each) in comparison to erythromycin (E), cotrimoxazole (SXT) and amoxicillin-clavulanic acid (AMC). Kinetic studies of kill showed that CDR was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was observed after 6-8 h for many of the isolates tested. As expected, a PAE was observed when S. aureus was treated with CDR at MIC (range of individual values for 5 strains 0.8-1.5 h) and 4 x MIC (range 1.1-1.4 h). Moreover, CDR showed a significant PAE at both its MIC and 4 x MIC against S. pneumoniae (range 0.5-1.0 h and 0.9-1.1 h), H. influenzae (range 0.4-0.7 h and 0.4-0.8 h), B. catarrhalis (range 0.5-0.7 h and 0.65-0.95 h) and E. coli (range 0.5-0.6 h and 0.5-0.7 h). The good bactericidal activity and the significant PAE of CDR against Gram-positive and Gram-negative bacteria (including respiratory pathogens) are a promising indication for the clinical efficacy of this cephalosporin in several bacterial infections. PMID- 1292915 TI - Evaluation of cefixime biliary disposition in the isolated perfused rabbit liver model and in humans. AB - Cefixime is a new orally effective third-generation cephalosporin. It inhibits a wide variety of Gram-positive and Gram-negative bacteria, especially most of the Enterobacteriaceae. Since extrarenal excretion processes have been reported to account for 60% of cefixime systemic clearance we have endeavoured to determine the place taken up by biliary excretion of unchanged cefixime in this pattern. We initially used the isolated perfused rabbit liver technique. Six perfusions were performed. Cefixime concentrations were measured by HPLC chromatography. After addition of a single 10-mg dose of cefixime to the circulating blood, biliary elimination of the drug proved to be very low, since only 0.28 +/- 0.15% of the dose was recovered during the 3-h perfusion period. The rate of cefixime biotransformation in the liver was found to be 16.2%. In contrast, the data obtained in humans highlight substantial biliary excretion of the drug. In six healthy volunteers submitted to duodenal aspiration and receiving a single 200-mg i.v. dose of cefixime, drug levels in duodenal fluid were at least fivefold greater than the simultaneous concentrations in serum. Biliary excretion of cefixime was further investigated in ten cholecystectomized patients provided with T-tube drainage: following a single 200 mg oral dose of cefixime, Cmax in bile reached 56.9 +/- 70 mg/l, that is about 25 times as high as Cmax in serum, 2.3 +/- 0.85 mg/l. Drug levels in choledochal bile proved to be sustained, since a concentration of 4.3 +/- 3.7 mg/ml was still observed 20 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292916 TI - Comparison of the effects of midecamycin acetate and clarithromycin on gastrointestinal motility in man. AB - The gastrointestinal motor effects of the macrolide antibiotic, clarithromycin, were compared with those of midecamycin acetate. The method of investigation consisted of intraluminal pressure measurements in the gastric antrum and upper small intestine by means of a low compliance perfused catheter system. Six healthy volunteers participated in the single-blind, placebo-controlled study of both interdigestive and postprandial gastrointestinal motility. Clarithromycin was administered by mouth in a dose of 250 mg b.i.d.; midecamycin acetate was given in a dose of 600 mg b.i.d. The effect of midecamycin acetate on gastric antral and jejunal motility was not significantly different from that of placebo. This was true for both the interdigestive and the postprandial phases of gastrointestinal motility. Oral treatment with clarithromycin (250 mg, b.i.d.) resulted in a statistically significant increase in the postprandial number of antral contractions per hour as well as in the postprandial antral motility index, as compared to placebo. PMID- 1292917 TI - The action of propionyl-L-carnitine on the vasal endothelium: increased t-PA synthesis and a decrease in the activity of PAI-1. A preliminary study. AB - In this study the authors attempted to restore the coagulative fibrinolytic homeostasis that is compromised in peripheral vascular disease. Eleven patients with arterial disease, eleven with venous disease and seven healthy volunteers underwent oral treatment using 3 g of propionyl-L-carnitine divided into thrice daily doses for a period of 20 days. (1 g t.i.d.). This quaternaria amine is able to correct tissue hypoxia by increasing ATP and energy production and has the capacity to prevent alterations in endothelial membrane permeability. The authors observed a significant increase of t-PA synthesis on the 10th day of therapy in the arterial disease and control groups. All three groups showed a significant increase in t-PA synthesis on the 20th day of therapy. A significant decrease in PAI-1 activity was observed on the 10th and on the 20th day of therapy in both the patient groups, but not in the control group. Although the exact pathological mechanisms of peripheral vascular disease are complex and in many aspects still unknown, it is now absolutely certain that there is a pathogenetic role of functional imbalances. An important part is played by the reduction in t-PA synthesis and the increase in PAI-1 activity, and the authors conclude that it is necessary to use pharmaceutical substances to restore proper equilibrium. PMID- 1292918 TI - Controlled study on L-carnitine therapeutic efficacy in post-infarction. AB - A controlled study was carried out on 160 patients of both sexes (age between 39 and 86 years) discharged from the Cardiology Department of the Santa Chiara Hospital, Pisa, with a diagnosis of recent myocardial infarction. L-carnitine was randomly administered to 81 patients at an oral dose of g 4/die for 12 months, in addition to the pharmacological treatment generally used. For the whole period of 12 months, these patients showed, in comparison with the controls, an improvement in heart rate (p < 0.005), systolic arterial pressure (p < 0.005) and diastolic arterial pressure (NS); a decrease of anginal attacks (p < 0.005), of rhythm disorders (NS) and of clinical signs of impaired myocardial contractility (NS), and a clear improvement in the lipid pattern (p < 0.005). The above changes were accompanied by a lower mortality in the treated group (1.2%, p < 0.005), while in the control group there was a mortality of 12.5%. Furthermore, in the control group there was a definite prevalence of deaths caused by reinfarction and sudden death. On the basis of these results, it is concluded that L-carnitine represents an effective treatment in post-infarction ischaemic cardiopathy, since it can improve the clinical evolution of this pathological condition as well as the patient's quality of life and life expectancy. PMID- 1292919 TI - The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs). AB - Recent studies on the maturation of auditory brainstem evoked responses (ABRs) present conflicting results, whereas only sparse reports exist with respect to the maturation of middle latency auditory evoked responses (MLRs) and auditory cortical evoked responses (ACRs). The present study reports the effect of preterm birth on the maturation of auditory evoked responses in low risk preterm infants (27-34 weeks conceptional age). The ABRs indicate a consistent trend towards longer latencies for all individual ABR components and towards longer interpeak latencies in preterm infants. The MLR shows longer latencies for early component P0 in preterm infants. The ACRs show a remarkable difference between preterm and term infants. At 40 weeks CA the latencies of ACR components Na and P2 are significantly longer in term infants, whereas at 52 weeks CA the latencies of the same ACR components are shorter in term infants. The results support the hypothesis that retarded myelination of the central auditory pathway is partially responsible for differences found between preterm infants and term infants with respect to late ABR components and early MLR component P0. Furthermore, mild conductive hearing loss in preterm infants may also play its role. A more complex mechanism is implicated to account for the findings noted with respect to MLR component Na and ACR components Na and P2. PMID- 1292920 TI - Neonatal cerebral ultrasound, neonatal neurology and perinatal conditions as predictors of neurodevelopmental outcome in very low birthweight infants. AB - To determine the assessments before discharge from the intensive care unit, that will predict outcome most accurately, a prospective longitudinal study in a cohort of 79 high risk VLBW children was conducted from birth to 3.6 years of age. Birthweight, gestational age, obstetrical and neonatal optimality, neonatal neurological examinations and neonatal cerebral ultrasound were studied in relation to outcome. The best predictor for outcome was a simple cerebral ultrasound classification according to the presence or absence of ventriculomegaly and intraparenchymal damage of any cause. Infants with normal neonatal cerebral scans or abnormal scans without ventriculomegaly almost invariably had a normal neurological outcome. In infants with cerebral lesions with ventriculomegaly the incidence of normal neurological outcome decreased to less than 50%. Intraparenchymal damage was associated with cerebral palsy as well as other (mental and sensori) handicaps in over 85% of the cases. Neonatal neurological examinations at preterm age had additional value in predicting neurological outcome especially in the group with ventriculomegaly. Neither birthweight, nor gestational age, obstetrical or neonatal optimality were independent variables in the prediction of outcome in high risk VLBW children at 3.6 years of age. PMID- 1292921 TI - Neonatal blood pressure levels of preterm infants who did and did not develop chronic lung disease. AB - The aim of this study was to assess if, in the neonatal period, there were differences in the blood pressure (BP) level of infants who did and did not develop chronic lung disease. If such differences were demonstrated to exist, we also hoped to determine influencing factors. Forty infants, consecutively admitted to our unit and who remained there throughout the neonatal period were studied. Twenty infants, median gestational age 29 weeks (range 27-32), did not develop CLD (non-CLD group) and 20 infants, median gestational age 26 weeks (range 24-32), developed CLD. Systolic BP was assessed using a non-invasive Doppler technique on day one and subsequently at weekly intervals. After day one and throughout the neonatal period BP levels, corrected for birthweight, were higher in the CLD group compared to the non-CLD group, by a mean of 5 mmHg. There was no significant difference between the numbers of infants in each group receiving theophylline or pancuronium. Significantly more infants in the CLD group had an umbilical catheter inserted and their catheters remained in situ significantly longer, a median of 8 days compared to a median of one day in the non-CLD group. We conclude that even in the neonatal period infants who develop CLD may have a modest elevation of BP, this is associated with prolonged umbilical arterial catheterisation. Our results, however, suggest that significant hypertension in infants who develop CLD, occurs after the neonatal period. PMID- 1292922 TI - A comparison of height, weight and head circumference of primary school children living in deprived and non-deprived circumstances. AB - Heights, weights and head circumferences were obtained from two groups of primary school children: 1016 children from throughout Oxfordshire, a rural county with few areas of deprivation, and 219 children from an economically deprived part of the city of Newcastle on Tyne. Compared to Tanner and Whitehouse standards, Oxfordshire children were significantly taller, but not heavier, while the Newcastle children were significantly shorter and markedly lighter. Mean head circumference values were lower in the Newcastle than the Oxfordshire children. Existing national growth standards are outdated when applied to children in acceptably advantaged circumstances while impoverished children still fall below these standard in a pattern suggestive of under nutrition. PMID- 1292923 TI - Umbilical cord insertion: normal location in neonates. AB - The distances between the xyphoid appendix and the insertion point of the umbilical cord (XU) and between the xyphoid appendix and upper edge of the pubic symphysis (XP) were measured in 201 newborn infants. The mean ratio XU/XP was 0.62 (S.D. 0.044) with no differences between sexes nor correlations with weight or length. Ratios lying between 0.53 and 0.71 can be considered as within the normal range. PMID- 1292924 TI - Doppler velocimetry in cerebral vessels of small for gestational age infants. AB - Using the duplex Doppler system, blood velocity was measured serially at two sites of the anterior cerebral artery (ACA) and in the middle cerebral artery (MCA) during the first 3 days of life, in eight term, small for gestational age (SGA) infants (birthweight, 2179 +/- 230 g; mean +/- S.D.), and 13 term, appropriate for gestational age (AGA) infants (3376 +/- 441 g). All infants in both groups had normal Apgar scores and none manifested signs of respiratory distress. At 1 h post partum, the average MCA mean velocity in the SGA group (25.8 +/- 6.9 cm/s) was higher than that in the AGA group (19.6 +/- 5.7 cm/s), whereas the average values of the two ACA sites did not differ between the groups. A significantly increased value of the average mean velocity as compared to the value at 4 h post partum was reached earlier in the AGA group at all three vessel sites. The pulsatility index (as defined by Gosling) was lower at all vessel sites up to 72 h in the SGA group. Pulse pressure was significantly lower in the SGA group due to increased diastolic blood pressure. We suggest the results imply a state of cerebral vasodilation in the SGA infants and a poor ability to respond with an increased perfusion in the frontal regions supplied by the ACA. Changes in blood pressure and cerebral haemodynamics appear to exist in SGA infants in the absence of postnatal hypoxia which might explain the vulnerability of the growth-retarded infant to perinatal hypoxia. PMID- 1292925 TI - Impact of early growth delay on subsequent fetal growth and functional development: a study on diabetic pregnancy. AB - In the first trimester of type-1 diabetic pregnancy, the embryo and fetus are often smaller than normal (early growth delay). We examined the impact of early growth delay on subsequent growth (birth weight) and functional development near term (organizational level of fetal behavioral states) in 21 and 10 fetuses of diabetic women, respectively. There was no relationship between the degree of early growth delay and birth weight (centiles). Mean growth delay per fetus in early diabetic pregnancy was negatively correlated with the occurrence of no coincidence between behavioral state parameters at 36 weeks (R = -0.59; P < 0.05). These results indicate that disorders occurring in early life may underlie abnormal functional development in later life, whereas (catch up) growth is mainly determined during the second half of pregnancy. PMID- 1292926 TI - Essential fatty acid status during early human development. AB - Preliminary studies indicated that the EFA status of normal neonates is marginal, if not insufficient. Since a better knowledge of the physiology of maternal-fetal essential fatty acid transfer is relevant for nutritional recommendations during pregnancy, we investigated the course of the fetal EFA status during fetal development by analysing the absolute (micrograms/g dry fetal tissue) and relative (% of total fatty acids) fatty acid composition of phospholipids in human fetal tissue, (n = 40, gestational age 5-15.2 weeks). The total content of fatty acids (mg/g dry fetal tissue) increased with gestational age. The absolute amount of virtually all fatty acids increased with maturation. Linoleic acid (18:2n-6, LA), however, was an exception. A highly significant, negative correlation between gestational age and the relative amount of LA in fetal tissue was observed during this first trimester of pregnancy. Our results show that the fetal-maternal difference in linoleic acid content observed at birth, initiates early in pregnancy. Since the fetus completely depends on the mother for its EFA supply, the maternal EFA status was measured simultaneously by analysing the fatty acid composition of phospholipids, isolated from plasma and red blood cells. Significant positive correlations between maternal rbc and fetal tissue were found for the relative amounts of LA. Similar relationships were observed between maternal plasma and fetal tissue for the relative amounts of cervonic acid (22:6n-3), the most abundant essential fatty acid in brain and retina. The relation between maternal and fetal EFA in phospholipids is significantly more pronounced after 10 weeks of gestation than before. This might be connected with the increased importance of the placenta with respect to maternal-fetal fatty acid transfer after 10 weeks of gestation. PMID- 1292927 TI - Failure of expression of the phenobarbital-induced enhancement of UDP glycosyltransferases in native, sealed endoplasmic reticulum vesicles from rat liver. AB - Conflicting data have been published regarding the effects of phenobarbital treatment on bilirubin UDP-glucuronyltransferase activity in native liver microsomes. Recent evidence suggests that the bilirubin UDP-glycosyltransferase system faces the interior of microsomal vesicles, and that expression of its activities in sealed microsomes may be rate-limited by transport of UDP sugars across the membrane. These observations raise the possibility that the reported variability in the effects of phenobarbital may reflect differences in integrity of the membrane in microsomal preparations. We examined the effect of phenobarbital on bilirubin UDP-glucosyltransferase and the UDP glucuronyltransferase activities towards bilirubin, 4-nitrophenol, and 1-naphthol using native rat liver microsomes with verified vesicle integrity. Phenobarbital induced microsomes in which the membrane permeability barrier was eliminated by pretreatment with detergent displayed markedly higher UDP-glycosyltransferase activities towards all tested substrates compared with activities in similarly disrupted microsomes from untreated rats. In contrast, none of the transferase activities tested were significantly enhanced by phenobarbital treatment when the enzymic activities were assayed in sealed microsomes. Addition to the enzyme assay mixture of UDPGlcNAc, a presumed physiological activator of the UDP glucuronyltransferases, failed to expose the enhanced UDP-glucuronyltransferase concentration in phenobarbital-induced sealed microsomes. Our findings are consistent with the idea that transport of UDP sugar across the membrane may be rate-limiting for expression of UDP-glycosyltransferase activities in sealed microsomes. Quantitative assessment of membrane integrity is an essential prerequisite in experiments designed to study the regulation of the microsomal UDP-glycosyltransferase system. PMID- 1292928 TI - Hyperoxia elevates Cu,Zn-superoxide dismutase of endothelial cells as detected by a sensitive ELISA. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of bovine Cu,Zn-SOD. Accuracy of the ELISA and specificity of the antibody for cell free extracts was established by: (1) measurement of antigen levels of bovine endothelial cell extracts reconstituted with pure antigen, and (2) immunoblotting with affinity purified antibody. The ELISA was highly sensitive and 0.05-0.10 ng of pure antigen could be accurately detected, which allowed the measurement of Cu,Zn-SOD in as few as 250 endothelial cells. With utilization of the ELISA for detection, DEAE-cellulose chromatography patterns of endothelial cell Cu,Zn-SOD overlapped those of pure bovine erythrocyte Cu,Zn-SOD. Exposure of cells in culture to 80% O2 for 48 h increased the relative abundance of the Cu,Zn-SOD as measured by the ELISA by 1.8-fold. Thus, endothelial cells in culture respond to hyperoxia by enhanced production of Cu,Zn-SOD protein. The ELISA developed in this study may be useful for assessing other factors that regulate cellular production of Cu,Zn-SOD. PMID- 1292929 TI - Tissue-mediated regeneration of ascorbic acid: is the process enzymatic? AB - Ascorbic acid's function in animals is attributed in part to the ease with which it reduces potentially damaging components, such as reactive free radicals. After more than six decades of speculation and laboratory efforts, the mechanisms by which ascorbic acid is maintained in the useful, reduced state remain uncertain. Previous attempts to isolate the enzymes that reduce the partially and the fully oxidized metabolites of vitamin C are reviewed. Some speculation on why dehydroascorbate reductase (EC 1.8.5.1) has not been purified from animal tissues is presented. PMID- 1292931 TI - Characterization of ecto-nucleoside triphosphatase on A-431 human epidermoidal carcinoma cells. AB - Hydrolysis of extracellular ATP and other nucleoside phosphates by A-431 human epidermoidal carcinoma cells was studied. The hydrolysis of extracellular ATP by these cells required either Mg2+ or Ca2+, and either cation could be replaced by Co2+, Fe2+, or Mn2+. Nucleoside triphosphates (ATP, GTP, CTP, UTP, and dTTP), but not nucleoside diphosphates, were hydrolyzed by the cells with Km and Vmax values similar to those for ATP (0.9-1.1 mmol/l and 6-10 nmol Pi formed/10(6) cells, respectively). The hydrolysis of ATP was inhibited strongly by ATP-gamma S and AMPPNP, and weakly by AMPCPP and ADP-beta S, but not by AMPCPP or AMPCP. Since the hydrolysis of [gamma-32P]ATP was inhibited by all these nucleoside triphosphates, the binding site for ATP is presumed to be the same as that for the other nucleoside triphosphates. All these results indicate that ecto-ATPase activity associated with A-431 cells is due to ecto-nucleoside triphosphatase. The nucleotide specificity shown in the present study indicates that ecto nucleoside triphosphatase associated with A-431 cells is a molecule different from P2-purinergic receptors which can be stimulated specifically with nucleoside phosphates like ATP, ADP, UTP, UDP, and GTP, but not by other nucleotides. PMID- 1292930 TI - A rapid and strong increase of plasminogen activator induced by experimental anaphylaxis in rabbits. AB - Anaphylactic shock was induced in rabbits by injecting bovine serum albumin (BSA) as an antigen. Measurements of the enzyme activities in the fibrinolytic system confirmed that a rapid and strong increase of plasminogen activator (PA) was induced during anaphylaxis. The euglobulin fibrinolytic activity (EFA) as estimated by the plasminogen-rich fibrin plate method rose significantly, peaking at 15 min after the BSA injection (when the arterial pressure was minimum). However, EFA was not detected by the plasminogen-poor fibrin plate method. The tissue-type PA (t-PA) activity using the natural substrate plasminogen increased significantly with a peak at 15 min. The amidolytic activity also simultaneously increased significantly using the t-PA substrate, H-D-Ile-Pro-Arg-pNA. The plasminogen activator inhibitor (PAI) activity remained at baseline levels until 30 min, but rose fourfold at 90 min. The main plasma fibrinolytic enzyme which increased in anaphylaxis was proved by zymography to be t-PA with a molecular weight (MW) of 69,000. PMID- 1292932 TI - Effect of thyroid hormones on 5'-nucleotidase of isolated rat fat cells. AB - 5'-Nucleotidase was measured in isolated fat cells from normal, hypothyroid and hyperthyroid rats. This was done to find out whether thyroid hormones had an effect on the production of adenosine by the fat cell. The results showed that 5' nucleotidase is modified when the rats received injections of 3,3',5-triiodo-L thyronine (T3). There was no change in the enzyme in hypothyroidism or when T3 was added to incubation of cells. PMID- 1292933 TI - Retinal oxidation activity and biological role of human cytosolic aldehyde dehydrogenase. AB - The major cytosolic aldehyde dehydrogenase isozyme (ALDH1) exhibits strong activity for oxidation of retinal to retinoic acid, while the major mitochondrial ALDH2 and the stomach cytosolic ALDH3 have no such activity. The Km of ALDH1 for retinal is about 0.06 mumol/l at pH 7.5, and the catalytic efficiency (Vmax/Km) for retinal is about 600 times higher than that for acetaldehyde. Thus, ALDH1 can efficiently produce retinoic acid from retinal in tissues with low retinal concentrations (< 0.01 mumol/l). The gene for ALDH1 has hormone response elements. These findings suggest that the major physiological substrate of human ALDH1 is retinal, and that its primary biological role is generation of retinoic acid resulting in modulation of cell differentiation including hormone-mediated development. PMID- 1292934 TI - Detection of creatine kinase isoenzymes as tumoral markers of rhabdomyosarcoma. AB - We analyzed the expression profile of isoenzymatic fractions of creatine phosphokinase (EC 2.7.3.2) isotypes MM, MB and BB in three cell lines derived from embryonic rhabdomyosarcomas and a normal counterpart cell line. Electrophoretic data showed that the BB fraction was consistently expressed de novo, in contrast with its counterpart in normal tissue. The BB fraction may serve as new tumoral marker for the diagnosis of rhabdomyosarcoma. In addition, the appearance of macrocreatine kinase type-1 in this type of neoplasm may serve to reinforce the diagnosis when rhabdomyosarcoma is suspected. PMID- 1292935 TI - Characterization of acatalasemia detected in two Hungarian sisters. AB - Acatalasemia was detected in 2 sisters of a Hungarian family. The pedigree of the family showed hypocatalasemia in the children of the patients and in 1 of their brothers, while the other members of the family had normal blood catalase activity. The biochemical characterization (catalase activity, electrophoretic migration, isoelectric point and enzyme stability) of the blood as well as tissue catalase of the acatalasemic patients yielded a catalase form which did not differ from normal. PMID- 1292936 TI - Platelet-activating factor (PAF-acether) formation in neonatal intestinal mucosa and in cultured intestinal epithelial cells. AB - We report the presence of platelet-activating factor (PAF-acether; 1-O-alkyl-2 acetyl-sn-glycero-3-phosphocholine) in small-intestinal and colonic mucosa of neonatal rats. The PAF-acether content was higher in the colon than in the small intestine, and was lower in the small intestine of 30-day-old animals than in 14 day-old animals. We also report that cultured intestinal epithelial cells (INT 407) produce PAF-acether when stimulated with the calcium ionophore A23187, and that homogenized INT 407 cells can degrade PAF-acether with the formation of lysoPAF-acether. These findings suggest that intestinal epithelial cells are able to produce and metabolize PAF-acether, a potent mediator of inflammation. The authors propose that this might contribute to the pathophysiology of inflammatory bowel disease. PMID- 1292937 TI - Evaluation of antioxidant treatment with superoxide dismutase in rat liver transplantation after warm ischemia. AB - In order to investigate the effects of the exogenously administered radical scavenger superoxide dismutase (SOD) on the orthotopic liver graft, livers from male Wistar rats were transplanted after subjection to 40 min of warm ischemia and 30 min of storage at 4 degrees C. SOD was given at the onset of ischemia and before reperfusion as a supplement (6,000 IU) to the washout solutions. 30,000 IU were infused into the recipient. SOD reduced tissue levels of thiobarbituric acid reacting substances at the end of ischemia (737 vs. 956 nmol/g; p < 0.01) and 60 min after the onset of reperfusion (629 vs. 947 nmol/g; p < 0.001) and preserved total adenine nucleotides after reperfusion (11.69 vs. 10.40 mumol/g; p < 0.01). Survival 2 weeks after transplantation was 18% (2/11) in the SOD group versus 10% (1/10; nonsignificant) in untreated animals. It is concluded that SOD protects the ischemically altered liver from radical mediated peroxidation and preserves hepatic energy stores upon reperfusion. However, in our model no major improvement in organ viability could by achieved. PMID- 1292938 TI - Hepatic energy metabolism during hypothermic storage and reperfusion using different protecting solutions. AB - Effects of 5 cold storage solution on hepatic high energy phosphate metabolism and metabolic function were examined using the isolated perfused rat liver. University of Wisconsin (UW), Euro-Collins (EC), and 2 cardioplegic solutions, Bretschneider's HTK and St. Thomas Hospital solution, were studied for their protective capacity. Krebs-Henseleit bicarbonate buffer (KHB) was used to point out the effect of simple hypothermia. Liver ATP, total adenine nucleotides and energy charge losses were significantly lower during 21 h of storage in UW preserved livers. Also, only UW-protected livers were able to complete regeneration of ATP and total adenine nucleotides after 1 h of reperfusion, whereas EC, HTK, St. Thomas and KHB stored livers only showed minimal regeneration. Concerning metabolic function, UW protected livers liberated significantly less LDH and sGOT as well in the 21-hour storage solution as into the perfusate under reperfusion conditions. This study demonstrates the capability of UW solution in liver preservation by its ability to maintain and restore high energy phosphates. PMID- 1292939 TI - Effect of hyperbaric oxygen and surgery on experimental gas gangrene. AB - An experimental model of clostridial gas gangrene was developed in rats and the therapeutic value of surgical debridement alone versus a combination of surgery and hyperbaric oxygen (HBO) was assessed. The infection was produced by an intramuscular injection of Clostridium perfringens microorganisms. The mortality of untreated rats was 100%. The mortality of the rats treated only with surgery was 37.5% compared to 12.5% when HBO was added to the treatment protocol (p < 0.01). In the group treated with HBO and surgery 82.5% of the animals healed completely and were able to walk normally, whereas the corresponding figure in the rats treated with surgery alone was 12.5% (p < 0.001). In the present experimental setting HBO treatment was an important therapeutic adjunct to surgery reducing both mortality and morbidity. PMID- 1292940 TI - Portal venous pressure following splenectomy in patients with portal hypertension of differing etiology. AB - To clarify the effect of splenomegaly on portal hemodynamics in patients with portal hypertension and esophageal varices, manometric studies were carried out before and after splenectomy during an operation for esophageal varices. The 118 patients evaluated retrospectively had underlying liver cirrhosis (LC) (62), idiopathic portal hypertension (IPH) (42), and extrahepatic portal occlusion (EHO) (14). The weight of the spleen did not differ significantly among the three diagnostic groups: 640 +/- 473.5 g for LC, 780 +/- 414.6 g for IPH, and 683 +/- 457.2 g for EHO. Before splenectomy, portal pressure was significantly elevated in the patients with EHO (410 +/- 85.2 mm H2O) as compared to either the LC or IPH groups (348 +/- 64.1 and 348 +/- 73.5 mm H2O). Following splenectomy the reduction of portal pressure was significantly greater in the EHO group (29 +/- 15.5%) than in either the LC (18 +/- 17.4%) or IPH (19 +/- 17.0%) groups. Each group was subdivided according to severity of splenomegaly: marked (spleen weight > or = 500 g) or slight (spleen weight < 500 g). Patients with LC and marked splenomegaly showed a reduction in liver function parameters as shown by the prolongation of indocyanine retention rate at 15 min as compared to those with slight splenomegaly. Though it is not statistically significant, the average portal pressure tended to be higher among those with marked splenomegaly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292941 TI - Comparative cell culture effects of shape memory metal (Nitinol), nickel and titanium: a biocompatibility estimation. AB - Nitinol is an equiatomic alloy of nickel and titanium which has been attracting increasing interest in the field of biomedical engineering. To quantify toxicity as a preliminary evaluation of biocompatibility, inhibition of mitosis in human fibroblasts in tissue cultures exposed to test materials is an accepted screening method, although a dose-effect relationship had never been investigated. In this experiment, the effect of an increasing dose exposure to Nitinol, nickel or titanium on human fibroblasts in cell cultures was tested in subgroups in comparison with a control group. The results showed that nickel induces a significant (p < or = 0.05) inhibition of mitosis in human fibroblasts, whereas no significant effects of this kind were found for titanium or Nitinol. According to the results of these studies, Nitinol is to be considered in this respect biocompatible and comparable to titanium, which would seem to justify application as a surgical implant. PMID- 1292942 TI - [Chemical plaque control]. AB - Most of the diseases with which dentists must deal with are related to microbial plaque and bacterial infection. The mechanical removal of supra- and subgingival plaque by the patient and by the dentist respectively, is time consuming and exacting, furthermore it is not one hundred per cent successful. There has been extensive search for many years for chemical agents that could supplement or even substitute mechanical plaque removal. Many chemical agents delivered in different ways were tested. Chemotherapeutics of various modes of action have to meet pharmacokinetic and biological requirements. Apparently the ideal anti-plaque agent is not yet available, so that they should be reserved for well defined clinical situations and short--or medium--term application. PMID- 1292943 TI - [Covering of residual palatal defects by a combination of prostheses]. AB - We carried out successful oral rehabilitation of a 17 year old female patient, who had a congenital cleft lip and palate. Having been operated on several times, she still had residual cleft on her palate. We used removable metal plate clipped to the cemented circular bridge to cover the communication. It is known that fixed prostodontics are more acceptable for patients, and cause less psychical difficulties, especially in cases of patients with congenital disorders, which have already caused psychical disturbances. PMID- 1292944 TI - [The effect of surface etching on tensile strength]. AB - The aim of this study was to investigate the effect of different partial size of corundum used by sand blasting on the surface roughness and on the tensile strength. The conclusions of the authors were as follows: 1. The maximum values of tensile strength were measured when 200-250 microns corundum was used. 2. The values of the R(a) and Rmax were grown proportionally with the grain of corundum, but it was not resulted in the same increase of the tensile strength. 3. After the tensile test the residue of the bonding agent on one surface of the test piece pairs, always remained significantly higher, than on the other, but this phenomenon cannot be explained by the differences between R(a) and Rmax within the test-piece pairs. PMID- 1292945 TI - [Diabetes care and research in Europe. The St. Vincent Declaration Action Program. A french adaptation by the Conseil Superieur du Diabete]. PMID- 1292946 TI - Induction and prevention of type 1 diabetes mellitus by viruses. AB - Genetic factors and environmental factors are thought to be involved in the pathogenesis of insulin-dependent diabetes mellitus Type 1. Viruses, as one environmental factor, may act as primary injurious agents to beta cells or as triggering agents for autoimmunity. Some viruses such as EMC-D and Coxsackie B4 can induce Type 1 diabetes by infecting and destroying beta cells in genetically susceptible mice. In addition, certain species of monkey, such as Patas, show elevated blood glucose levels and depressed insulin secretion after infection with Coxsackie B4 virus. An occasional case of Type 1 diabetes mellitus appears to be associated with the infection of beta cells with Coxsackie B viruses. In addition, Coxsackie B4 virus may also generate viral antigen-specific cytotoxic T cells which may cross-react with a beta cell-specific autoantigen leading to autoimmune Type 1 diabetes. In the case of viral triggering of autoimmune Type 1 diabetes, certain viruses (eg, retrovirus in NOD mice and rubella virus in hamsters and humans) may alter a normally existing beta cell antigen into an immunogenic form or might induce a new antigen, leading to beta cell-specific autoimmune insulin dependent diabetes mellitus. In addition, other viruses (eg, Kilham's rat virus in DR-BB rats) could generate antigen-specific T effector cells which may cross-react with a beta cell-specific autoantigen. In contrast to the induction of diabetes, viruses can prevent the development of diabetes. Inoculation of DP-BB or NOD mice with lymphocytic choriomeningitis virus reduced the incidence of diabetes or prevented the disease by disordering particular lymphocyte subsets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292947 TI - [Is it possible to improve the teaching methods of physicians who instruct patients? Comparative analysis of the same courses given before and after teacher's training]. AB - The goal of the present study is to compare the pedagogic involvement of two groups of doctors, both of which were in charge of teaching the same courses to diabetic patients. Important structural differences were-shown exit between the two series of courses. The first group of ten doctors (who not undergone any pedagogic training) applied either ex-catedra teaching methods or proceeded by systematically asking questions to the patients. These scholastic methods led to passive attitudes in their patients in listening and replies to a large number of questions. In the second group of ten doctors (who had undergone pedagogic training) learning practices and a stimulating didactic material were used which resulted in more diversified and more attractive responses in the participation of the patients. Providing improved didactic means on the behalf of the doctors is aimed at obtaining better knowledge from patients who have themselves to assume the self-management of their treatment. PMID- 1292949 TI - [Should one be afraid of hypoglycemia?]. PMID- 1292948 TI - Evaluation of a dipstick test for microalbuminuria in three different clinical settings, including the correlation with urinary albumin excretion rate. AB - A dipstick test for microalbuminuria was compared with urinary albumin excretion and urinary albumin concentration. Elevated urinary albumin excretion was defined as > 30 mg/24 h, elevated urinary albumin concentration in early morning urine as = > 20 mg/l and sticks = > 20 mg/l were considered positive. 1,071 samples with urinary albumin concentration 20-200 mg/l from 258 diabetic subjects were evaluated in three settings: I. 3 trained nurses testing samples from day-clinic diabetic patients. Sticks v.s. urinary albumin excretion sensitivity 86%, specificity 97%, predictive value of negative test 97%, correlation coefficient 0.79. Values for same setting but v.s. urinary albumin concentration were almost identical. II. 1 laboratory technician testing not-hospitalised diabetic patients: Sticks v.s. urinary albumin concentration: sensitivity 91%, specificity 85%, predictive value of negative test 95%, correlation coefficient 0.82. III. 58 general practitioners testing not-hospitalized diabetic patients: Sticks v.s. urinary albumin concentration: sensitivity 66%, specificity 92%, predictive value of negative test 83%, correlation coefficient 0.70. CONCLUSIONS: In the hands of trained nurses and laboratory technician the Micral-Test showed good correlation with urinary albumin excretion and urinary albumin concentration for day-clinic and not-hospitalized patients and can be recommended as a screening tool. General practitioners obtained a lower sensitivity probably due to lack of experience and incorrect handling of the sticks leading to systematical errors. Training in the use of the stick must be emphasized, since under such circumstances the results are satisfactory. PMID- 1292950 TI - [Study of a specific gene: cloning, sequencing and deduced information]. PMID- 1292951 TI - Local oscillations of frog skeletal muscle sarcomeres induced by subthreshold concentration of caffeine. AB - Different intracellular processes are selectively controlled by a signalling system based on transient rises or oscillations of cytoplasmic calcium concentration, which transmit extracellular signals at subcellular level. When treated with a subthreshold concentration of caffeine, skeletal muscle cells provide a suitable preparation to study mechanisms which generate repetitive calcium transients. Based on optical diffraction measurements of local contractions of individual sarcomeres, we have shown substantial enhancement of spontaneous repetitive calcium release in the presence of subthreshold caffeine concentration. Calcium release propagates to neighbor calcium sources and forms slow contraction waves. A power spectra density analysis has revealed parameters of the time course of these events. However, substantial amounts of calcium released in sarcomeres are not synchronized. PMID- 1292952 TI - Force-frequency relations in hypertrophic heart muscle: a mathematical model for excitation-contraction coupling. AB - Static and dynamic chrono-inotropic responses were recorded from both normal and hypertrophic rat auricular myocardium. The slope of the static force-frequency relation for hypertrophic hearts was steeper than that for control hearts. Computer experiments were designed to study the cellular mechanisms underlying the changes in the force-frequency response associated with heart hypertrophy, with the aid of a mathematical model for excitation-contraction coupling in rat heart. A set of equations was derived which permitted to study the effects on the chronoinotropic relations of both the geometrical dimensions of cardiomyocytes and the sarcoplasmic reticulum, and of the variation in activity of mechanisms for Ca movements through the sarcolemma and the sarcoreticular membrane. A comparison of data obtained from simulated and real experiments suggested that the features characteristic of force-frequency relations for hypertrophic heart are a result of an enhanced volume of intracellular Ca-stores rather than of the total volume of the cardiomyocyte. PMID- 1292953 TI - Temperature studies of glyceraldehyde-3-phosphate dehydrogenase binding to liposomes using fluorescence technique. AB - Interaction of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase with negatively charged liposomes was investigated as a function of temperature. This interaction affects the temperature-dependent conformational transition in the enzyme and exerts stabilizing effect on the protein structure. It can be seen from the fluorescence quenching experiments that the accessibility of tryptophanyl residues and isoindol probe fluorophores (covalently bound with the protein amino groups) for a dynamic quencher, acrylamide, is altered upon binding. This accessibility represented by effective quenching constant (Keff) strongly depends on temperature for unmodified enzyme and for the enzyme adsorbed on liposomes, it is nearly constant over a wide range of temperatures. PMID- 1292954 TI - On the correlation of myopia and intelligence. AB - A pleiotropic relationship between intelligence and myopia has been shown to exist. Large eyes (as measured by axial length) have been shown to lead to myopia, and large brains have been shown to be more intelligent. I hypothesized that the myopia/intelligence relationship could arise because a single genetically controlled mechanism affects both brain size and eye size. This hypothesis has testable implications. PMID- 1292955 TI - Outcomes of weight-loss programs. AB - We examined the results of a stratified random sample of 50 weight-loss studies conducted in the 1980s for weight change, change in overweight percentage, and improvement in physical health during treatment and follow-up. The typical participant was a White, middle-class woman 48% over her average weight before treatment, who lost 12.8 lb during a 13-week treatment program and then regained 4.3 lb over the next 6.5 months. Treatment efficacy was not improved when only the most successful treatment conditions were examined or when the studies conducted at the end of the decade were compared with earlier studies. Only one study examined change in physical health during weight loss, and only one study showed that participants moved from clinical to nonclinical levels of obesity. In light of these results, we argue that treating obesity through dieting techniques may be a misdirected goal. PMID- 1292956 TI - African-American and Puerto Rican drug use: personality, familial, and other environmental risk factors. AB - Using a family interactional theoretical framework giving primacy to the mutual attachment between parent and child, we examined the interrelationship of acculturation, ecological factors, family, personality, peers, and drug context domains with drug use in an inner city sample. We also assessed the extent to which family protective factors mitigated against risks for drug use from most of the other domains. The sample consisted of 695 African-American and 637 Puerto Rican 7th-10th graders who answered the questionnaire while listening to it on personal tape players in their classrooms. The results of hierarchical regression analyses sufficiently supported the hypothesized sequence of interrelationships in both ethnic groups to substantiate our developmental model of drug use. We also found protective buffers common to both ethnic groups and buffers specific to each group. The implications of the results for targets and timing of intervention in the path to drug use are discussed. PMID- 1292957 TI - The "temporalis-inhibitory reflex" in post-lumbar puncture headache. AB - Nausea and rigidity of the neck muscles, typical symptoms of post-lumbar puncture syndrome (PPS), may also be found in patients suffering from chronic headache of the tension-type. A decreased duration of the late suppression period of temporal muscle activity indicating a central disturbance of pericranial muscle control, can be observed in these patients. We have studied the temporalis-inhibitory reflex in 47 neurological inpatients requiring lumbar puncture. There were no significant differences of latencies or durations of temporalis silent periods between patients with and without PPS before, and 48 h following, lumbar puncture. PMID- 1292958 TI - Corneal sensitivity during and outside attacks of cluster headache. AB - Corneal sensitivity has been studied in cluster headache (n = 38) and controls (n = 16). The patients were studied either during remission (n = 20), interparoxysmally in a bout (n = 17), or during attacks (spontaneously occurring attacks (n = 5) and nitroglycerin-provoked attacks (n = 6). For the measurements, a Cochet-Bonnet esthesiometer was utilized. This esthesiometer has a 6 cm long, adjustable nylon monofilament, which can be reduced in length by 0.5 cm at a time, the length of the filament determining the pressure exerted onto the corneal surface. All controls sensed the pressure at 6.0 cm filament length. In 5 cluster headache patients (remission, n = 4; cluster period, n = 1) a slight reduction in corneal sensitivity was found. No statistical difference was, however, found between any of the groups tested, and there was no asymmetry as far as averages were concerned. PMID- 1292959 TI - Hemicrania continua and chronic paroxysmal hemicrania: a comparison of pupillometric findings. AB - Pupillometric studies were carried out in 9 patients with chronic paroxysmal hemicrania (CPH), in 10 patients with hemicrania continua (HC) and in age- and sex-matched controls (n = 12-17). Studies were carried out in the basal condition and after instillation of 2% tyramine, 1% OH-amphetamine, or 1% phenylephrine. The pupillary response to tyramine in HC was more marked than in controls on a percentage increase basis, but not so much when the increment is calculated in absolute values. In this series, there was no asymmetrical response (relative miosis on the symptomatic side) like in previous case reports. The pupil reaction was less in HC than in CPH after hydroxyamphetamine instillation and without any marked asymmetry. There was no definite evidence of supersensitivity to a directly acting sympathicomimetic agent, phenylephrine. No gross abnormalities as regard the sympathetic function in HC was thus observed. The asymmetry on tyramine testing differed in CPH and HC (most marked in HC). No major emphasis should probably be attached to this finding, since on testing with OH amphetamine, a similar substance, this finding was not reproduced. PMID- 1292960 TI - Cardiovascular effects of TENS: heart rate variability and plethysmographic wave evaluation in a group of normal subjects. AB - Transcutaneous electrical nerve stimulation (TENS) is generally used in controlling pain. Side effects are not frequent, but sometimes do happen. Among these, automatic disturbances have been described. The purpose of the investigation was to study high frequency TENS effects on heart rate variability and the plethysmographic wave. Results showed no change in heart rate variability parameters (Standard Deviation, Mean Square Successive Difference) despite an increase in R-R interval, while a decrease in the amplitude of the plethysmographic wave was observed. This study seems to point out that high frequency TENS does not modify the neural control to the heart while a sympathominetic effect is shown on the peripheral plethysmographic wave. PMID- 1292961 TI - Sneddon's syndrome and renal carcinoma. Case report. AB - A patient with Sneddon's syndrome in association with renal neoplasm is discussed. The association has not been reported before and raises questions concerning the pathogenesis of vascular proliferation in Sneddon's syndrome. PMID- 1292962 TI - Electrocortical power spectrum changes induced by microinfusion of corticotropin releasing factor into the locus coeruleus in rats. AB - Rat corticotropin-releasing factor (CRF) microinfused unilaterally or bilaterally into the locus coeruleus (LC) of awake, chronically cannulated rats produced a dose-dependent ECoG desynchronization and behavioral activation. ECoG spectra analysis revealed a significant decrease of total voltage power and of 0.25-3 and 3-6 Hz frequency bands. These effects were prevented by a pretreatment into the same site with alpha-hCRF, a selective antagonist at CRF receptors and by alprazolam, a benzodiazepine derivative. In conclusion, the present results indicate that CRF produces its behavioral and ECoG activating effects by interaction with specific receptors located on LC neurons. PMID- 1292963 TI - Clinical features of patients suffering from Streptococcus milleri infections--a retrospective analysis. AB - We examined the clinical records of patients from whom S. milleri was isolated at Kyushu University Hospital from January 1987 through December 1988. Sixty-one patients were treated in 64 episodes with drainage or antibiotics. Oral and nasopharyngeal infections were observed in 27 cases, intrathoracic infections in 13, urogenital infections in 8, intraabdominal infections in 6 and skin and subcutaneous infections in 6. Except for acute bronchitis and urogenital infections, all of them were suppurative. As to underlying diseases, 21 patients had malignancies and 6 had diabetes mellitus. Leukocytopenia was not observed in any of the patients. S. milleri can be eradicated by treatment but it is sometimes replaced by other organisms. However, considering its tendency to cause suppurative infections, its pathogenic significance should be taken into account and patients should undergo surgical drainage combined with antibiotic therapy. PMID- 1292964 TI - [Clinicopathological study on the proliferation and differentiation of laryngeal carcinoma and dysplasia]. AB - It is important to examine the proliferative activity of cells in the laryngeal carcinoma and dysplasia for the decision of the clinical treatment and the presumption of the prognosis. I studied here the proliferative activity with three indications, such as the measurement of nuclear DNA contents by flow cytometry, immunohistochemistry of Proliferating Cell Nuclear Antigen (PCNA) and intake of bromodeoxyuridine (BrdU). Furthermore, I compared the proliferative activity with cellular differentiation, which was investigated by immunohistochemistry of involucrin, a marker of human mature suprabasal squamous epithelia. Flow cytometric DNA analysis was performed in 69 patients of laryngeal carcinoma and in 15 patients of dysplasia. In laryngeal carcinoma, 41 cases (59%) had DNA aneuploid pattern, and in dysplasia, 6 cases (40%) represented aneuploid group, and 27% and 11% per 1 hour in diploid group, respectively. The mean of DNA Index (DI) was 1.21 in the carcinoma and 1.13 in the dysplasia. In the cases of recurrent carcinoma and transformed carcinoma, aneuploid pattern was predominant and DI was high. I performed double staining of BrdU and involucrin in these cases. The former is an index of cellular proliferation and the latter is a marker of the differentiation, as described above. These two markers showed reciprocal relationship in normal squamous cell layers, dysplasia and many areas of squamous cell carcinoma. But, some cells of the carcinoma in advanced stage represented concomitantly positive result in these two markers. This finding suggests the biological disorder in these carcinoma cells and requires the follow up examination of these cases. PMID- 1292965 TI - Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice. AB - In naive mice, ibogaine at a tremorigenic dose (30 mg/kg, ip), did not produce antinociception but did potentiate the antinociceptive potency of morphine in the tail-flick test. In morphine-dependent mice, ibogaine did not eliminate withdrawal symptoms but significantly increased the number of repetitive vertical jumps induced by naloxone, whatever the duration of the chronic morphine treatment. By comparison, repetitive jumping induced by alpha-napthoxyacetic acid (alpha-NOAA), a non-convulsant drug which induced jumping without affecting other morphine-withdrawal signs, was not significantly modified by ibogaine. These results indicate that while acute antinociceptive effects of morphine are modulated by ibogaine, this drug, shown to alleviate opiate dependence in man, does not attenuate in mice opioid withdrawal manifestations. PMID- 1292966 TI - Inhibition of [3H] gamma-aminobutyric acid release from guinea-pig hippocampal synaptosomes by serotonergic agents. AB - We studied the effects of (m-trifluoromethyl-phenyl)piperazine (TFMPP) and quipazine on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes loaded with [3H]GABA.TFMPP and quipazine inhibited the K(+)-evoked release of [3H]GABA dose-dependently (IC50 = 153 and 123 microM, respectively). Serotonergic antagonists such as methiothepin (0.1, 0.3 and 1 microM), ketanserin (0.1, 0.3 and 1 microM), dihydroergotamine (0.1 microM), metergoline (0.1 and 0.3 microM), methysergide (0.3 microM), propranolol (1 microM) and yohimbine (1 microM) did not significantly alter the inhibitory effect of TFMPP on [3H]GABA release suggesting that neither 5-HT1 nor 5-HT2 receptors are involved in this process. By contrast, the effect of TFMPP was diminished by selective 5-HT3 receptor antagonist: MDL 72222 (0.3 microM), tropisetron (0.3 and 1 microM), ondansetron (0.3 microM) and metoclopramide (1 microM). Tropisetron (1 microM) and ondansetron (0.3 microM) also inhibited significantly the quipazine effect whereas methiothepin (1 microM), dihydroergotamine (0.1 microM), yohimbine (1 microM) and ketanserin (1 microM) were ineffective on the quipazine inhibition of [3H]GABA release. Our results show a serotonergic modulatory effect on the K(+) evoked [3H]GABA release from guinea-pig hippocampal synaptosomes by receptors which are neither 5-HT1, 5-HT2 or 5-HT4. They appear to be pharmacologically related to the 5-HT3 type but different from the 5-HT3 ionic channel receptors. PMID- 1292967 TI - Treatment with growth hormone-releasing hormone (GHRH) 1-44 in children with idiopathic growth hormone deficiency: a randomized double-blind dose-effect study. The GHRH European Multicenter Study (GEMS) Group. AB - One hundred and eleven pre-pubertal children (70 boys, 41 girls, aged 2.5 to 14.3 years) with growth failure (height 2 SD below the mean for chronological age (CA) and height velocity (HV) below the 10th percentile for bone age) due to idiopathic growth hormone deficiency (peak plasma GH < 20 mUI/1 to two standard provocative tests) were treated with GHRH 1-44 NH2. Patient stratification in two classes was performed according to body weight; in each class, patients were randomly allocated to one of seven GHRH doses, from 30 to 300 micrograms/day. GHRH was injected subcutaneously, every evening, for six months in a double-blind fashion. No relationship was found between the absolute or incremental HV during treatment and the dose (range from 1.3-23.1 micrograms/kg/day) of GHRH. However, HV (cm/year) increased from 3.8 +/- 0.1 (mean +/- SEM) before treatment to 6 +/- 0.2 during six months treatment and 47 patients (42%) increased their HV up to at least the mean normal HV for bone age (catch-up growth). Low titer antibodies to GHRH were found in 19 patients (17.1%) at six months; no adverse effect was observed. Our results suggest that patients showing catch-up growth were older, had a height closer to the mean for chronological age and a slower pre-treatment height velocity. Failure to demonstrate a relationship between GHRH dose and changes in growth velocity might be explained by the combination of a placebo effect, insufficient frequency of GHRH administration and heterogeneity of the population. PMID- 1292968 TI - Lack of effect of isradipine on cyclosporin pharmacokinetics. AB - The influence of isradipine as a long acting form (IcazR LP 5 mg) on cyclosporin pharmacokinetics was studied in six hypertensive renal transplant patients (mean age 37 yrs; mean body weight 62 kg). These patients received a mean daily cyclosporin dose of 307 mg in two equal intakes. Isradipine was orally administered once a day at a dose of 5 mg before the morning cyclosporin intake. Cyclosporin kinetics was assessed over a 0-12-h period, the day before (D-1) and 13 days (D+13) after isradipine treatment. Whole blood concentrations of cyclosporin were determined by radioimmunoassay (RIA) using the SandimmuneR-RIA kit (specific and non-specific monoclonal antibodies). Area under the blood concentration-time curve (AUC), the maximum blood concentration (Cmax) and the time to reach Cmax (Tmax) on D-1 and D+13 were not significantly different whatever the specificity of the RIA method. For example, the mean AUC +/- sd values were 5,247 +/- 2,255 (D-1) vs 5,317 +/- 1,675 (D+13) microgram.1(-1).h for the specific and 20,905 +/- 8,317 vs 19,327 +/- 5,758 microgram.1(-1).h for the non-specific determinations. Therefore, the pharmacokinetics of cyclosporin is not influenced by co-administration of isradipine at a therapeutic dosage. Moreover, the clinical results show that isradipine treatment was effective after 13 days administration (mean systolic blood pressure 132 vs 158 mm Hg, P < 0.05 and mean diastolic blood pressure 77 vs 93 mm Hg, P < 0.05 in supine position), and well tolerated throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292969 TI - Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers. AB - The purpose of the present study was to determine whether erdosteine and its metabolites (substances containing thiol groups) can prevent the alteration of the chemotactic function of polymorphonuclear cells (PMN) from peripheral blood induced by cigarette smoke of eight healthy non-smoking volunteers, when incubated in vitro before smoke exposure, and whether oral treatment with erdosteine (900 mg/day) for two weeks might restore the chemotaxis of PMN, either from eight healthy or from 16 chronic bronchitic smokers. The chemotactic stimuli in vitro were casein, lipopolysaccharides (LPS), and formyl-methionyl-leucyl phenyalanine (FMLP). The results of the study in vitro have confirmed that PMN from non-smoking volunteers shows a reduced chemotactic responsiveness when exposed in vitro to smoke. This can be partially prevented in a dose-related manner by pre-incubation with erdosteine, its metabolites, cysteine, and glutathione (metabolites I and II being at least 10 times more active than the intact substance and the known biological standards also containing thiol groups). The experiment on PMN from healthy smokers (in a double-blind crossover design versus placebo) has indicated that the chemotaxis can be improved only after treatment with erdosteine. The same observation has been made in the experiment on PMN from smokers affected by chronic bronchitis (in a double-blind design versus placebo with two distinct groups). In these patients the phagocytic and bactericidal activities of PMN were not affected by the smoke and therefore, neither one was influenced by erdosteine treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1292970 TI - Malotilate completely inhibits CCl4-induced liver cirrhosis in rats: biochemical and morphological analysis. AB - Malotilate, diisopropyl 1,3-dithiol-2-ylidenemalonate, is a relatively recently synthesized hepatotrophic chemical substance. Its inhibitory effect on rat liver cirrhosis induced by carbon tetrachloride (CCl4) was biochemically and morphologically investigated for 10 weeks, since this chemical had been reported to suppress liver damage caused by CCl4 or in vitro collagenogenesis of human fibroblasts. Concomitant administration of malotilate with CCl4 completely suppressed liver cell necrosis and markedly inhibited fatty change of hepatocytes in the first three weeks of the experiment. During the six to ten weeks of the experimental period, liver cirrhosis was perfectly inhibited by malotilate. Previously established liver cirrhosis, however, could not be normalized by malotilate treatment. Precise mechanism of the inhibitory effect of malotilate on liver cirrhosis is not elucidated, but this substance is clearly effective for preventing liver cell damage and/or liver cirrhosis caused by CCl4. PMID- 1292971 TI - Emotion and identification of environmental sounds and electroencephalographic activity. AB - Eight environmental sounds, i.e., playing the harp, cuckoo's song, sound of the waves, cock's crow, noise of the subway, alarm of a clock, sound of a dentist's drill, scratching of the blackboard, and their temporally reverse sounds were presented for 20 sec to 16 college students in a sound-attenuated chamber. The subjects were requested to estimate the degree of pleasantness-unpleasantness and confidence in identifying each sound 10 sec after presentation. Electroencephalography was recorded at C3, C4, O1 and O2 (International 10-20 system), and the mean EEG powers of delta, theta, alpha-1, alpha-2, beta-1 and beta-2 bands during the sound presentations were computed by a signal processor. The results were as follows: 1) Even when the loudness and frequency component of the sounds were equivalent, there was big difference in pleasantness unpleasantness estimation among the environmental sounds. 2) Inaccuracy in identifying the sounds presented backwards neutralized the pleasantness unpleasantness estimation. 3) Powers of theta and low frequency alpha bands were higher during presentation of the pleasant sounds than during presentation of the unpleasant sounds. 4) Alpha activity was more closely related with subjective confidence in sound identification than with pleasantness-unpleasantness estimation of sound. These findings suggest that pleasantness-unpleasantness estimation of environmental sounds depends not only on their loudness level or frequency component but on the accuracy in sound identification and that modification of sound identification may be useful in alleviating the environment noise problem. Alpha activity seems to be closely related to the recognition of sound, but further research is needed on EEG activity in the relationship between the emotional state and sound identification. PMID- 1292972 TI - Optic atrophy, sensorineural hearing loss and polyneuropathy--a case of sporadic Rosenberg-Chutorian syndrome. AB - We report on a 41-year-old woman with slowly progressive motor dominant polyneuropathy, optic atrophy and sensorineural deafness, but without any known familial feature. These neurological manifestations were in accordance with the syndrome reported by Rosenberg and Chutorian in 1967 (Rosenberg-Chutorian syndrome), a unique form of Charcot-Marie-Tooth disease. The syndrome was first reported to be autosomal dominant in trait, but subsequently recessive forms and sporadic ones have also been described. Nerve biopsy and neurophysiological studies including electromyography, nerve conduction velocities, somatosensory evoked potentials, auditory brainstem responses, and visual evoked potentials revealed the axonopathic involvement of the central nervous system as well as the peripheral nervous system. Since neurophysiological aspects of this particular syndrome have not been well studied, these results would provide some insight into the understanding of this disorder. PMID- 1292973 TI - Growth-hormone-binding protein in patients with acromegaly. AB - The present study was undertaken to investigate the possible regulatory effect of chronic exposure to human growth hormone (hGH), in patients with acromegaly, on growth-hormone-binding protein (GH-BP). Nineteen patients with active acromegaly, before, during or after treatment, comprised the subjects of this study. Serum GH was measured by radioimmunoassay and GH-BP by a binding assay with dextran-coated charcoal separation. The specific binding of [125I]hGH (1 ng) obtained with 50 microliters serum was expressed as a percentage of total cpm. To evaluate the impact of the lower GH-BP on GH activity, we studied the effect of acromegalic serum on hGH displacement of [125I]hGH binding to GH receptors in rabbit liver membranes. Compared to normal controls (11.43 +/- 0.37%), the acromegalic patients had low serum levels of GH-BP (5.45 +/- 0.40%; p < 0.001), which correlated negatively with serum GH levels (p < 0.01). In 7 patients, GH-BP normalized within 2-3 months of successful therapy. The lower GH-BP was due to a reduction in binding capacity, whereas binding affinity remained unchanged. Acromegalic serum, with its low GH-BP, resulted in a shift to the left of the GH displacement curve when compared with normal human sera: IC50 values were 7.47 +/ 0.29 and 11.19 +/- 0.84 ng (p < 0.02) for acromegalic and normal human sera, respectively. We conclude that acromegaly is characterized by low levels of GH-BP due to a decrease in serum-binding capacity. The decrease in GH-BP may render the acromegalic serum GH relatively more active in the GH receptor assay. PMID- 1292974 TI - Bone turnover in overt and subclinical hyperthyroidism due to autonomous thyroid adenoma. AB - Parameters of bone turnover were measured in 20 premenopausal women affected by autonomous thyroid adenoma: 7 patients were suffering from overt hyperthyroidism with raised values of free thyroid hormones; 13 were clinically euthyroid and had normal values of free thyroid hormones. In all cases serum TSH concentrations were below the lower normal limit of our laboratory (< 0.4 mU/l). Eleven healthy premenopausal women were studied as a control group. Patients with overt hyperthyroidism disclosed a significant enhancement of both bone resorption (increased serum calcium and urinary excretion of hydroxyproline) and bone formation (increased serum levels of osteocalcin and alkaline phosphatase) when compared both to controls and to patients with subclinical hyperthyroidism. No significant alterations of bone metabolism parameters were found in patients with subclinical hyperthyroidism in comparison with controls. Therefore, in premenopausal women affected by autonomous thyroid adenoma the bone turnover appeared to be significantly increased when the serum values of free thyroid hormones were raised in the group of patients with overt hyperthyroidism. PMID- 1292975 TI - Insulin activity: stimulatory effects of cinnamon and brewer's yeast as influenced by albumin. AB - Cinnamon and Brewer's yeast extracts have been shown to potentiate the action of insulin in isolated adipocytes. In this study, isolated rat epididymal adipocytes were used to evaluate the influence of bovine serum albumin on insulin activity as affected by cinnamon and Brewer's yeast extracts. Albumin at 0.01-0.1% decreased the insulin stimulatory effects of cinnamon from 11.8- to 5.3-fold and 2% albumin decreased this effect to near control levels. Conversely, the insulin enhancing properties of Brewer's yeast remained low in the presence of less than 0.25% albumin but subsequently increased 2.8-, 4.8- and 5.6-fold in the presence of 0.25, 0.50 and 1.0% albumin, respectively. In the absence of added insulin, increased activity of the insulin-stimulated utilization of glucose by both extracts was observed but only Brewer's yeast extract displayed additive effects when tested at higher insulin levels. Due to the inhibitory and enhancing effects of albumin on the insulin activity of cinnamon and Brewer's yeast, respectively, it is suggested that the effects of albumin be assessed when evaluating the insulin-enhancing effects of other substances using isolated adipocytes. PMID- 1292976 TI - Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys. AB - Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10 15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates. PMID- 1292977 TI - The sole presence of the testis-determining region of the Y chromosome (SRY) in 46,XX patients is associated with phenotypic variability. AB - Four cases of XX patients with testis development are reported. The aim of this study was to describe their clinical features and to see if there was any relationship between phenotypes and the presence of Y material. Several human Y derived sequences including the SRY probe were used to analyze the DNA of the patients. Yp material including the pseudo-autosomal region and SRY was detected. The cases reported in this study confirm that XX true hermaphrodites cannot be distinguished from XX males on the basis of their genotypes. There is no relationship between clinical and anatomical phenotypes and the presence of Y material. SRY does not warrant a complete and normal testis differentiation. Although similar in some features with Klinefelter's syndrome patients, XX males exhibit specific clinical manifestations due to the lack of Y-specific genes. PMID- 1292978 TI - Evolutionary origins of intercellular communication systems: implications for mammalian biology. AB - Traditionally, the two major systems of intercellular communication (i.e. the nervous and endocrine systems) were considered separate functional and anatomical entities. Recent studies have provided evidence that the biochemical elements of these systems have common early phylogenetic origins and have suggested that, with the exception of their anatomical diversity, all the systems of intercellular communication are biochemically similar. On the basis of these findings, we suggest that the overlaps between the nervous and endocrine systems, the widespread tissue production of hormones, and other phenomena are now more easily understood. PMID- 1292979 TI - Role of insulin-like growth factors and growth hormone in reversing catabolic states. AB - The insulin-like growth factors (IGFs) mediate the anabolic effects of growth hormone or protein synthesis in muscle and skeletal tissues. Administering growth hormone to normal volunteers who have been made catabolic by caloric restriction improves the nitrogen balance. The studies described illustrate that administration of somatomedin-C (IGF-I) to catabolic normal volunteers also results in improved nitrogen balance and, unlike growth hormone, does not induce insulin resistance. Growth hormone was anabolic in patients with severe chronic obstructive lung disease and resulted in improved chest wall muscle strength. Both IGF-I and growth hormone have the potential to improve muscle mass and function in patients who are catabolic due to the severity of their underlying disease state. PMID- 1292980 TI - Growth hormone actions on fat distribution and metabolism. AB - The secretion of growth hormone (GH) and the mass and distribution of body fat are linked through a complex series of interactions. There is increasing evidence that a GH/fat cycle exists and that elements of this cycle may possess regulatory functions. The essential elements of the cycle are: (1) GH-deficient individuals are often obese and lose body fat when they are treated; GH is lipolytic in vitro and causes an acute release of free fatty acids (FFA) when administered in vivo; (3) circulating FFA inhibit the pituitary release of GH by most secretagogues, including growth hormone releasing hormone, and (4) the obese state is characterized by a defect in GH release which can be reversed by weight loss. PMID- 1292981 TI - The effects of human growth hormone and prednisone on whole body estimates of protein metabolism. AB - Human growth hormone (GH) increases estimates of whole body protein synthesis, but has little effect on the rates of proteolysis either post-absorptively or when absorption occurs during a meal. In contrast to insulin, GH stimulates protein synthesis in skeletal muscle tissue. Prednisone in high doses induces protein catabolism and has been used as a controlled model for catabolic illness. Prednisone increases the rates of proteolysis and amino acid oxidation, but has little effect on estimates of protein synthesis. The administration of high doses of GH together with prednisone prevents the protein catabolic effects of prednisone alone. Thus, GH may provide a new management strategy in patients with significant protein catabolic conditions. PMID- 1292982 TI - Growth hormone and insulin interactions. AB - Insulin and glucose clamp techniques were used to investigate insulin action and insulin secretion during childhood. Preliminary results suggest that growth hormone (GH) therapy leads to changes in glucose, amino acid and insulin responses that are qualitatively similar to those observed during puberty. Furthermore, the insulin resistance normally seen during puberty may be restricted to peripheral glucose metabolism. In patients with Turner's syndrome, data indicate that there is an increase in the glucose-stimulated insulin response which is exaggerated by GH treatment. PMID- 1292983 TI - Gender and sexual orientation in relation to hypothalamic structures. AB - Animal experiments have provided evidence for the presence of sex differences from the synaptic level up to behaviour. Although sex differences in the human brain may have been presumed implicitly since the days of Aristotle, research on the presence of functional and structural sex differences of the human brain started only relatively recently. The most conspicuous sex difference in the mammalian brain was described by Gorski et al. [1978] in the preoptic area (POA) of the rat hypothalamus. We found that the volume of a putative homologue of this sexually dimorphic nucleus (SDN) in the adult human hypothalamus was more than twice as large in men as in women and contained about twice as many cells. Recently a similar sex difference and volume has been described for the human bed nucleus of the stria terminalis and 'interstitial nuclei of the hypothalamus' (INAH). Sexual differentiation of the hypothalamus was generally believed to take place between 4 and 7 months of gestation. A life span study on the SDN of more than 100 subjects revealed, however, that only after the age of 2-4 years postnatally sexual differentiation becomes manifest by a decrease in volume and cell number in the female SDN. If sexual differentiation of the brain indeed takes place postnatally, not only chemical and hormonal factors may influence this process but also social factors. A prominent theory on the development of sexual orientation is that it develops as a result of an interaction between the developing brain and sex hormones. According to Dorner's hypothesis, male homosexuals have a female differentiation of the hypothalamus. This hypothesis was not supported by our observations on the SDN. Neither the SDN volume nor the cell number in the hypothalamus of homosexual men differed from that of heterosexual men. However, a difference in SCN cell number was observed in relation to sexual orientation. The volume and cell number of the SCN of homosexual men was twice as large as that of a reference group. During development, the SCN volume and cell counts reach peak values around 13-16 months after birth. At this age the SCN contains about the same number of cells as the SCN of adult male homosexuals, whereas in the reference group the cell numbers subsequently decline to the adult value, which is about 35% of the peak value.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1292984 TI - Genetic determinants of testis development in normal and abnormal individuals. AB - A candidate for the male sex determining gene 2 has recently been isolated. This gene, named SRY, has an expression profile consistent with a role in testis determination, is mutated in some XY females, and causes female to male sex reversal in transgenic mice. The cloning of this gene should facilitate the characterization of other genes in the testis determining pathway. PMID- 1292985 TI - Differentiation of the fetal gonad. AB - Gonadal differentiation may be divided into four stages: pregonadal, indifferent, primary sex differentiation, and secondary sex differentiation. Sertoli cells appear at 6-7 weeks and Leydig cells differentiate at 8 weeks, but in ovaries, primary sex differentiation occurs much later. Testosterone secretion peaks at 12 16 weeks causing male secondary sex development together with the appearance of anti-Mullerian hormone. Fetal testis is able to synthesize and secrete inhibins. Lower circulating luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in male than in female fetuses at midgestation suggest that the fetal pituitary is already responsive to the gonadal hormones. Placental human chorionic gonadotrophin may regulate testosterone synthesis at midgestation, and both LH and FSH are likely to have some regulatory effect on fetal gonads during the last third of gestation. PMID- 1292986 TI - Anti-mullerian hormone and Sertoli cell function. AB - Anti-mullerian hormone (AMH) is a glycoprotein that is produced by immature Sertoli cells and is responsible for the regression of mullerian ducts in male fetuses. It is a useful marker of testicular function in children, when anorchia is suspected and in intersex states. In the persistent mullerian duct syndrome, both AMH-positive and AMH-negative forms have been reported. In three cases of the latter, a mutation of the AMH gene is thought to have been responsible for the condition. PMID- 1292988 TI - Syndromes and genital dysmorphology. AB - External and internal genitalia can be malformed by genetic and environmental factors without involvement of sex chromosomes or fetal gonads. Thus, genital dysmorphology may be part of many syndromes of various etiology, such as monogenetic disorders, autosomal chromosomal abnormalities and non-random malformation syndromes of unknown etiology. Genital dysmorphology may also occur as a result of teratogenic effects following maternal ingestion of synthetic progestins. The genital manifestations in all these syndromes occur more commonly in males than in females. Penetrance and expression of these abnormalities tend to show great variability. PMID- 1292987 TI - Male pseudohermaphroditism: clinical management, diagnosis and treatment. AB - Male pseudohermaphroditism (MPH) is a disorder of sexual differentiation whereby the external genitalia are at variance with a male karyotype and the presence of testes. Abnormalities of Leydig cell function are an important cause of MPH, but postnatal age must be considered when interpreting the testosterone response when HCG stimulation is used as a diagnostic test. Androgen insensitivity is also a common cause of MPH; the specific defect in androgen receptor function is currently the subject of intense study, using a combination of biochemical assays and molecular analysis of the androgen receptor gene. The treatment of MPH is influenced by genital tissue responsiveness to androgens and the technical complexity of reconstructive surgical procedures. There is a need for information on the outcome of MPH treatment regarding pubertal development, sexual performance and fertility. PMID- 1292989 TI - Autoimmune polyglandular syndromes. AB - Autoimmune polyglandular syndromes originally defined by Blizzard, Maclaren and Neufeld were classified into three constellations based on the clinical clustering of the various component diseases. Type I and type II are reasonably well circumscribed entities with type III being an ill-defined group. The autoimmune nature of these diseases has been based on the presence of lymphocytic infiltration in the affected gland, organ specific autoantibodies in the serum, cellular immune defects and an association with the HLA DR/DQ genes or immune response genes. Autoantibodies to the various endocrine and non-endocrine tissues not only offer a diagnostic clue to the autoimmune nature of diseases but also can be used to identify asymptomatic individuals who are at risk of developing other component diseases of the syndrome. In this review the clinical and serological spectrum of type I and II APS will be discussed. PMID- 1292990 TI - Factors that affect depth perception in stereoscopic displays. AB - This study investigated several factors that affect depth perception in stereoscopic displays: half-image separation magnitude, separation direction (crossed vs. uncrossed), viewing distance, stimulus size, and exposure duration. The depth perceived under various combinations of levels of these factors was compared with depth predicted by the geometry of stereopsis. Perceived depth in the crossed-separation direction was frequently close to predictions, such that increases in separation and viewing distance produced appropriate increases in perceived depth. Depth in the uncrossed direction was frequently less than that predicted, especially for small stimuli presented at a long viewing distance, with a large half-image separation, and/or with a brief duration. Thus depth in both crossed and uncrossed directions equaled predictions only for large stimuli exposed for a long duration. PMID- 1292991 TI - Human stereopsis. AB - This paper reviews much of the basic literature on stereopsis for the purpose of providing information about the ability of humans to utilize stereoscopic information under operational conditions. This review is organized around five functional topics that may be important for the design of many stereoscopic display systems: geometry of stereoscopic depth perception, visual persistence, perceptual interaction among stereoscopic stimuli, neurophysiology of stereopsis, and theoretical considerations. The paper concludes with the presentation of several basic ideas related to the design of stereoscopic displays. PMID- 1292992 TI - Time stress and the processing of visual displays. AB - Selecting the appropriate display format for time-constrained tasks is the focus of the research presented in this paper. The effect of time stress on operator performance was assessed by manipulating the time available to process the display. Twenty people were trained as operators and instructed to identify the state of a system using either a digital display or a polygon display. Participants were required to reach a prespecified criterion in training and were then tested under time-constrained conditions. Time constraints were set at 100%, 50%, and 25% of each person's mean unpaced response times obtained during training. Results showed that response to the time constrained conditions was significantly affected by uncertainty and the type of display format. Discussion focuses on the effects of time stress on performance and the selection of displays for time-constrained tasks. PMID- 1292993 TI - Cervical cancer in India--strategy for control. AB - The available information on the incidence of cancers by site in India have indicated that of incidence of cancer of uterine cervix among women is by far the highest compared to other sites in women. The epidemiology of cervical cancer has been studied extensively in India and in other countries. The majority of factors related to cervical cancer are associated with sexual behaviour. The available evidence for control of cervical cancer is through secondary prevention, namely- early detection through Pap smear. In the present communication the alternative strategies with secondary prevention for control of cervical cancer is worked out. Taking into consideration the number of cervical cancer cases saved, number of woman years saved and the cost aspects the strategy at present for India should be to provide one life time screening for women at the age of 45 years. PMID- 1292994 TI - Primary tracheo oesophageal puncture our initial experience. AB - Our initial experience of 9 primary tracheo oesophageal punctures with Blom Singer prosthesis is reported. Patient selection was based on motivation, intelligence and socioeconomic status. Excellent speech resulted in 7 out of 9 patients (77%), with 2 failures (23%). There were no major complications. The results are encouraging, but a larger study is required to determine the role of this procedure in our conditions. PMID- 1292996 TI - Induction chemotherapy in non-metastatic high grade osteo sarcomas--results of pilot study at Cancer Institute (WIA), Madras. AB - Twelve patients with high grade osteosarcomas of the extremities were treated with two cycles of induction chemotherapy using adriamycin and cis-platinum and sandwich radiation between the two cycles (4000 rads). Ten patients underwent amputation or disarticulation, two patients had wide excision followed by endoprosthesis. The specimen was assessed for grade of necrosis. The Disease Free Survival at a minimum follow-up period of 26 months and median follow-up period of 35.5%. All the five patients who developed distant metastases had shown only a grade I necrosis in the tumour. PMID- 1292997 TI - Primary subglottic carcinoma. AB - Primary subglottic carcinoma is rare with a uniformly poor prognosis. We present our experience of eight such cases treated over a period of ten years. One patient had a mucoepidermoid carcinoma while the rest had a squamous cell carcinoma. A combination of surgery and radiotherapy was employed in five cases, while one case each underwent radiotherapy only, surgery only and salvage surgery following radical irradiation. Three cases died of locoregional failure within a year. The remaining five patients have been disease-free for six months to 3.5 years. PMID- 1292995 TI - Cancer profile in western Rajasthan. AB - A retrospective study of malignancy was conducted in the arid region of Western Rajasthan over a period of five years (1984 to 1988) to determine the frequencies of various malignancies. This was the region where India's first nuclear explosion took place in 1974. During this period 2662 new cancer cases were recorded. In males, Oropharyngeal and Hypopharyngeal malignancies topped the list. Males had an overall higher incidence than females (1.28:1). Most of the cases were between 31 years and 60 years with male peak at 60 years and female at 50 years. In females, cancer of the cervix formed the largest group followed by Breast cancer. A comparatively high rate of skin, urinary bladder, bone malignancy, lymphoma and leukaemia was observed in this region. Limited investigational facilities, lack of trained personnel, tough working condition, extremes of temperature, long distances in the desert region, with associated poverty, illiteracy and ignorance were some of the factors responsible for majority of the patients presenting in advanced stages. PMID- 1292998 TI - The dose time relationship in the radiotherapy of carcinoma of the cervix- application of CRE formalism. AB - A retrospective analysis of 291 patients with cancer of the uterine cervix treated with a combination of external and intracavitary radiotherapy was carried out. Patients were either treated with 45 Gy in 20 fractions by five fractions per week or with 42 Gy in 14 fractions by three fractions per week or with 42 Gy in 14 fractions by three fraction per week schedule by external radiotherapy. For brachytherapy the total dose was 24 to 32 Gy at a dose rate of 1.4 to 2.2 Gy per hour. Complication were correlated with total CRE values for point A (CRE TA) and for rectum CRE TR. Correlations of CRE TA with overall complication rate (p value < 0.05) and rectal complication rate (p value < 0.01) were excellent. Lack of correlation was observed between CRETR and overall complication rate (p value > 0.1) as well as rectal complication rate (p value > 0.1). In order to limit Grade II and III rectal and bladder complications to acceptable level, in combined external and intracavitary treatments, CRETA value of less than 2500 reu is suggested. PMID- 1292999 TI - Pure red cell aplasia and non-Hodgkin's lymphoma: a case report and brief literature review. AB - Pure red cell aplasia associated with lymphoproliferative malignancies other than thymoma is an uncommon occurrence. In the present paper we report a rare case of nodular non-Hodgkin's lymphoma with pure red cell aplasia who presented with symptoms related to anemia rather than the lymphoma and responded well to combination chemotherapy. PMID- 1293000 TI - Primary lymphoma of breast--report of six cases and review of literature. AB - Six patients of primary lymphoma of breast are presented. All our patients were female with median age of 46 years. Combination chemotherapy was the mainstay of treatment in all the patients. Five patients achieved complete remission of which two relapsed, one had a distant relapse and the other was local. Patient with distant relapse expired after a follow-up of 224 months whereas the one with local recurrence was well controlled with radiotherapy only. The role of combination chemotherapy to decrease the distant relapse and thereby mortality is discussed. PMID- 1293001 TI - Gastric transposition & deltopectoral flap for peristomal recurrence following total laryngectomy--a case report. AB - Stomal recurrence following laryngectomy presents a difficult problem with an incidence of 8.3-15%. Wide excision of the recurrence with mediastinal dissection, although the operation of choice,m is technically demanding and has a high morbidity and mortality. We recommend a technically easier procedure for reconstruction after palliative excision and present a case to illustrate it. PMID- 1293002 TI - Computed tomography evaluation of esophageal carcinoma. AB - Forty patients of histologically proven esophageal carcinoma were subjected to computed tomography (CT) with the objective to assess its reliability in preoperative evaluation of these patients. The findings were confirmed on surgery in twenty five of these patients, thought to be resectable. Bronchoscopy was performed to evaluate bronchial tree in cases of tumor of upper and middle third of esophagus. CT was found to be sensitive in predicting the location and size of tumor, in assessing invasion of tracheo-bronchial tree, spread to liver, celiac and left gastric nodes. However, it was not successful in picking up metastatic spread to local periesophageal nodes in five cases and celiac in one case. The study concluded CT should be carried out for preoperative evaluation of esophageal carcinoma to select operable cases and avoid unnecessary radicle surgery in advanced cases. PMID- 1293003 TI - Total leukocyte acid phosphatase and its isoenzymes in patients with leukemia. AB - Leukocyte acid phosphatase and its isoenzyme composition was studied in leukemic patients to determine the specificity of different isoenzymes in leukemic leukocytes. It was found that leukocyte acid phosphatase content is significantly increased in ALL, AML, and CML patients, while CLL patients had decreased levels of acid phosphatase. The distribution and intensity of leukocyte ACP isoenzymes vary in respective leukemic condition. Thus isoenzyme 'O' was predominant in AML and CML, while isoenzymes 1, 2 and 3 predominated in ALL. The lack of predominance of isoenzyme 3 was a feature in CLL patients. It was concluded that the isoenzyme patterns, though promising, presented inconclusive picture for diagnosis purpose and further studies on immunochemical characteristics of these isoenzymes are warranted to ascertain their cell specificity. PMID- 1293004 TI - Malignant systemic mastocytosis. AB - Malignant Systemic Mastocytosis is a very rare condition. Only about less than 40 well documented cases have been reported as per the available literature. The paper presents the case report of a 54 year old male patient who presented with huge hepatosplenomegaly and abdominal lymphadenopathy. Splenectomy specimen was 17 x 16 x 10 cm size with cut surface studded with numerous tiny 1-2 mm nodules. Histologic sections of spleen showed extensive mast cell (typical and atypical) infiltrates. Liver biopsy and abdominal lymphnode biopsy specimens and bone marrow smears also showed similar infiltration by mast cells. Special stains done for non-specific esterase and chloracetate esterase showed strong positivity for mast cells. The results of immunohistochemical and electron microscopic studies are also presented. PMID- 1293005 TI - Morbidity & mortality following craniofacial resections. AB - A seven year experience with twenty patients undergoing the craniofacial approach for excision of tumours of the paranasal sinus and orbit is presented. Results indicate a low postoperative morbidity and mortality with excellent cosmesis. Good palliation is achieved in the presence of extensive disease, while large tumours which would have been considered inaccessible can be resected. Its advantage recommend it as the treatment of choice for tumours of the orbit and paranasal sinuses. PMID- 1293006 TI - Neck metastasis from an occult primary--the Kidwai experience. AB - This study highlights our treatment policy in 26 cases of epidermoid metastatic carcinoma in the neck from a primary deemed occult after exhaustive examination of the Upper Aero-digestive Tract (UADT). Planned Radical Neck Dissection (RND) and post-operative radiotherapy (RT) has been the favoured approach in all neck nodes deemed resectable and a loco-regional control rate of 64% was obtaining using this combined modality approach. Pre-operative RT was utilised in three cases with nodal disease of borderline resectability and loco-regional control was achieved in one case. Three cases of massive neck metastasis initially deemed unrectable became amenable to surgical salvage after Radical RT with concurrently administered chemotherapy. Only one of these remained disease free. Overall loco regional control rate of 55 per cent could be achieved in 20 evaluable patients followed up for two years--three years (mean 30.5 months). Regional failures were noted in 25 per cent of patients while distant spread occurred in 15 per cent, thus accounting for an overall failure rate of 40 per cent. Manifest primaries were documented in 20 per cent, half of which could be salvaged and successfully controlled. PMID- 1293007 TI - Choroidal metastasis from primary adenocarcinoma of the esophagus--a case report. AB - Primary adenocarcinoma of the esophagus is uncommon and the incidence in the middle third is rare, accounting for about 0.7 percent to 1.5 percent. Metastasis of carcinoma to the eye is a rare occurrence. We report here a case of primary adenocarcinoma of the middle third of the esophagus with choroidal metastasis. PMID- 1293008 TI - Epidermoid cyst of the brain stem--a case report. AB - Epidermoid cysts occurring within the brain stem are extremely rare and only nine such cases are reported in the literature. In this report, we report a case of Intrapontine epidermoid cyst in a young female patient. PMID- 1293009 TI - Tumour induced osteomalacia: a report of two cases. A disease of defective matrix synthesis? AB - Tumour induced hypophosphataemic osteomalacia or rickets is a well delineated clinical entity. There is confusion, however, about the nomenclature and classification of the associated tumours. The tumour factor responsible for the biochemical abnormalities has also not been identified. We report here two cases: one, a 43 year old male with a soft tissue tumour in the left vastus medialis, and the other, a 25 year old female with a soft tissue tumour in the right anterior axillary fold. Reversal of biochemical abnormalities and clinical improvement occurred after removal of the tumour in both cases. Both tumours showed unusual morphology characterised by spindle cell component, large vascular spaces, osteoclast-like giant cells, calcification and ossification. The tumour in the second patient was benign, while the nature of the tumour in the first patient was debated. We speculate that defective matrix may be the cause of unusual histology of the tumours, and also the source of the phosphaturic factor. PMID- 1293010 TI - Extranodal sinus histiocytosis with massive lymphadenopathy--a case report. AB - Sinus histiocytosis with massive lymphadenopathy involving organs other than the lymph nodes is a rare event. A case of SIIML presenting with multiple skin and subcutaneous nodules and multiple osteolytic lesions is described. A search of the Indian literature revealed many cases of nodal SIIML, but none of the reported cases had prominent extranodal involvement. PMID- 1293011 TI - Malignant 'multinodular' oncocytoma of parotid gland--a case report and literature review. AB - The pathological findings in a multinodular malignant oncocytoma of the parotid gland in a male 62 years of age, with tumour infiltration into the adjacent skin and skeletal muscle and with regional lymph node metastasis is presented. PMID- 1293012 TI - Detection of rabies virus in different tissues of experimentally infected mice at preclinical and postclinical stages of the disease. AB - Rabies fixed virus (CVS) was passaged 10 times in mice by intramuscular (im) route followed by experimental inoculation of the titrated virus in 4 groups of mice with the dose of 0.1 ml of 1000 mouse (LD50 0.03 ml) using intracerebral (ic), intravenous (iv), intramuscular (im), intraocular (io), and intranasal (in) routes respectively. No marked variation in clinical signs due to variation of routes could be detected. Involvement of brain with io route could be detected even in preclinical stage. Although the virus could be detected in the postclinical stage in all the tissues under study (brain, skin, salivary gland and corneal impression), with io and ic routes spread of the virus was observed in comparatively higher concentrations. PMID- 1293013 TI - Prevention of development of tolerance and dependence to opiate in mice by BR-16A (Mentat), a herbal psychotropic preparation. AB - Chronic treatment with BR-16A (20-500 mg/kg) followed by saline on days 1 to 9 failed to produce any significant change in tail-flick latency from the saline pretreated group in mice. Repeated administration of BR-16A(20-500 mg/kg) for 9 days however, attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg). BR-16A (20-500 mg/kg) also suppressed, in a dose-dependent manner, the development of morphine dependence as assessed by naloxone (2 mg/kg) precipitated withdrawal on day 10 of testing. PMID- 1293014 TI - Effects of plant extract Centella asiatica (Linn.) on cold restraint stress ulcer in rats. AB - Extract of C. asiatica (Linn.) inhibited significantly gastric ulceration induced by cold and restraint stress (CRS) in Charles-Foster rats, Antiulcer activity of plant extract was compared with famotidine (H2-antagonist) and sodium valproate (anti-epileptic). Plant extract, formotidine and sodium valproate showed a dose dependent reduction of gastric ulceration. Plant extract increased brain GABA level which was also dose dependent. Pretreatment with bicuculline methiodide (specific GABAA-antagonist) at the dose level of 0.5 mg/kg im, reversed the antiulcerogenic activity of both plant extract and sodium valproate. Bicuculline as such did not induce gastric ulceration in normal rat. PMID- 1293015 TI - Stage specific effect during one seminiferous epithelial cycle following ethylene glycol monomethyl ether exposure in rats. AB - Stage specific effect of single oral dose (500 mg/kg body wt) of ethylene glycol monomethyl ether (EGME) was characterised during one cycle of seminiferous epithelium in rats. Maximum peritubular membrane damage and germinal epithelial distortion were observed at stages IX-XII. Cell death occurred during conversion of zygotene to pachytene spermatocytes (stage XIII) and between dividing spermatocytes and step I spermatids (stage late XIII-XIV). Profound effect was noted during first meiotic division than during second meiotic division. Presence of multinucleated secondary spermatocytes indicated cytokinesis arrest. The spermatogenesis was delayed and consequently frequency of tubules at stages I VIII was reduced by day 10. Many of the tubules were devoid of round spermatids on day 12. Possibly, EGME (or it's metabolite) distorted the barrier system at stages IX-XIV and damaged the cells mostly at stages XII-early XIV. PMID- 1293016 TI - In vitro study of rat uterus after chronic formaldehyde exposure. AB - To measure cholinergic, adrenergic and tryptaminergic receptor activity of formaldehyde (HCHO) in rat uterus, albino rats were treated with 5 and 10 mg/kg, ip HCHO for 30 days. Acetylcholine (ACh) in doses 1.33, 2 and 3 micrograms/ml produced mild to moderate contraction of isolated rat uterus in control group. HCHO had no effect on isolated rat uterus per se, however it reduced ACh and carbachol induced contraction and presence of adrenaline influences in respect of ACh and carbachol activity. Adrenaline per se had no effect in control preparations, but reduced carbachol induced contraction. Propranolol had no effect on rat uterus; but its presence in the bathing medium increased activity of adrenaline. 5-Hydroxytryptamine (5-HT) had no effect of its own on isolated rat uterus but its presence in the bathing medium enhanced contractions of carbachol and oxytocin. PMID- 1293017 TI - Iron bioavailability from Spirulina platensis, whole egg and whole wheat. AB - Bioavailability of iron from Spirulina was assessed in comparison with whole egg, whole wheat and standard ferrous sulphate using haemoglobin depletion repletion assay. Haemoglobin regeneration efficiency of Spirulina and whole egg was similar and significantly higher than that of whole wheat. The absorption of iron from Spirulina was significantly lower than that of ferrous sulphate and whole egg but significantly greater than that from whole wheat. PMID- 1293018 TI - Effect of centchroman and tamoxifen on protein patterns of fallopian tubes of rhesus monkeys, Macaca mulatta. AB - To study the effect of centchroman and tamoxifen on estrogen-dependent proteins of fallopian tubes of rhesus monkey, these antiestrogens were given with and without estradiol to ovariectomized monkeys. In absence of estradiol, both the compounds induced the synthesis of 130 and 95 K proteins. Concentration of 85 K protein was also increased markedly. These compounds, however, suppressed the estrogen stimulated synthesis of 130 K protein when administered with estradiol. The results show that both centchroman and tamoxifen possess estrogen agonistic as well as antagonistic properties and 130 K protein can be used as a marker protein to study estrogen action and for screening of antiestrogenic compounds in a primate model. PMID- 1293019 TI - Effect of diethylcarbamazine on acetylcholine and gamma amino butyric acid in Setaria digitata. AB - In vitro studies on the effect of neurotransmitter amino acids and amines on the motility of S. digitata showed that acetylcholine (Ach) had a stimulatory and gama amino butyric acid (GABA) an inhibitory effect on the parasite. When the worms were incubated in different concentrations of diethylcarbamazine there was a significant dose related increase in the level of Ach, and the level of GABA remained unchanged. Inhibition of acetylcholine esterase activity by diethylcarbamazine caused the accumulation of Ach in the synapses resulting in receptor desensitization and after a momentary stimulation causes paralysis of the parasite. PMID- 1293020 TI - An improvised method of laboratory colonization of Phlebotomus papatasi, the vector of cutaneous leishmaniasis. AB - A cyclic colony of P. papatasi was successfully established, using wild caught females. The major obstacle in the colonization was infestation of fungus, which was solved when bentonite, a dehydrant was mixed in the larval diet i.e., powdered and sterilized faecal pellets of rabbit. The average duration of development from egg to adult was 46.41 +/- 3.26 days. Females readily engorged on mouse, which was kept immobilized inside restrainer cages Majority of the fed females laid viable eggs, when confined in improvised styro-foam humidity chambers and survived after oviposition. In this process a stable, cyclic colony was established and it is now in F39 generation. PMID- 1293021 TI - Characteristics of monoclonal antibodies against porcine zona pellucida-3 and their functional relevance. AB - Seven monoclonal antibodies (MAs) against 55 kDa glycoprotein family of porcine zona pellucida (ZP3) reacting with either ZP3 alpha (MA-7, MA-27, MA-28) or ZP3 beta (MA-1, MA-2, MA-11, MA-30) have been described. MA-1, -2, -27, -28 and -30 do not recognize carbohydrate determinants as shown by their reactivity to the deglycosylated (DG) ZP3 alpha and ZP3 beta. Indirect immunoperoxidase studies showed that all MAs reacted with zona pellucida from porcine and monkey ovaries. Only MA-1 and -27 reacted with ZP from rabbit ovary as well, while none of the MAs recognised mouse ZP, MA-7, -11, -27, -28 and -30 inhibited in vitro, the zona lysis by trypsin as well as the binding of ZP3 to sperm membrane vesicle as investigated by ELISA. PMID- 1293022 TI - Patterns of inhibin and FSH localization in endometrium of baboon (Papio anubis) during menstrual cycle and early pregnancy. AB - Immunoreactive 10.5 KDa moiety of inhibin and hFSH was present in the baboon endometrium during menstrual cycle, early pregnancy and in castrated animals treated with steroid hormones, estrogen and/or progesterone. Endometrial differences during the menstrual cycle altered the intensity of immunostaining of inhibin and FSH. Maximum staining was observed in late luteal phase for both the hormones. In early pregnancy (35th day), the conceptus increased the staining for inhibin in the adjoining endometrial glands. Treatment of castrated animals with steroids for 14 days caused increased staining for inhibin. Maximum staining was observed when treated with estradiol or progesterone, whereas combination of estrogen and progesterone treatment decreased the staining reaction. In conclusion, both inhibin and FSH were localized in baboon endometrium and were under the influence of estrogen and progesterone. PMID- 1293023 TI - Seminal inhibin--prospects for immunocontraception. AB - Passive immunization of adult rats, hamsters and marmosets with rabbit anti seminal inhibin resulted in complete or partial block of fertility. The antiserum treatment presumably neutralized endogenous inhibin resulting in an unopposed rise in circulating FSH. This probably led to a refractoriness of the testes to FSH resulting in complete spermatogenic arrest. Nevertheless, there was no change in the mating behaviour of the animals. The antibodies also affected the epididymal spermatozoa by causing large scale agglutination. PMID- 1293024 TI - Antifertility effects in rats actively immunized with 80 kDa human semen glycoprotein. AB - A 80 kDa human sperm antigen has been identified using the serum of an infertile woman having circulating antisperm antibodies. The antigen was then purified to homogeneity by gel permeation chromatography using HPLC (protein PAK-125 column) system and on FPLC (superose-12 column) system. The antigen was found to be a glycoprotein. The antigen was mainly localized in the postacrosomal region of the human sperm, while it was localized in the head region of the rat sperm as demonstrated by immunofluorescent staining. The presence of this antigen was also demonstrated in the human prostate and endometrium and in the rat testis; epididymis and the prostate by immunocytochemical staining. The purified protein upon active immunization in female rats caused infertility in 100 percent animals. While in male rats it caused infertility in 90 percent animals. On morphometric analysis of testicular tissue it was observed that there was no significant change in spermatogonia and spermatocytes, but significant decrease in spermatids and sperm number as well as daily sperm production in the immunized male rats. The epididymal spermatozoa were markedly reduced in number and were largely found to be agglutinated. The results suggest that 80 kDa human sperm antigen appears to be a suitable candidate for immunocontraception both in male and female. PMID- 1293025 TI - Dual regulatory action of prostatic inhibin (10.7 kDa) on DNA synthesis. AB - Present studies deal with the role of inhibin in proliferation and growth. The effect of inhibin on incorporation of 3H-thymidine in prostatic DNA in vivo as well as by NRK-49F and Balb/c3T3 cell lines in vitro, was investigated. Also studied the immunocytochemical localization of inhibin in normally proliferating and differentiated tissues of human prostate and endometrium. The in vivo studies revealed a suppression of 3H-thymidine uptake both in ventral (33%) and dorsolateral (26%) lobes of rat prostate. Interestingly, the histology of inhibin treated rat prostate manifested amidst the epithelial lining, an appearance of apoptotic bodies which are considered to be indicative of cell death. Further, the immunocytochemical studies for localization of inhibin showed intense staining in the differentiated human prostate and endometrium as compared to the respective proliferative tissues. Is inhibin kept suppressed in these proliferating tissues, because it is antiproliferative? The present in vitro experiments demonstrated that, at low inhibin concentrations, the incorporation of 3H-thymidine is stimulated while at higher doses it is suppressed. Thus, it is clear that prostatic inhibin seems to have a concentration-dependent dual role in the regulation of DNA synthesis. PMID- 1293026 TI - Interrelationship between ovine follicular fluid inhibin and serum albumin. AB - Ovine follicular fluid inhibin (oFF-I) as isolated in this laboratory, proved to be a monomeric protein (M(r).65 kDa). It was found to share very many of the physico-chemical characteristics of ovine serum albumin (oSA)-such as molecular size, iso-electric point, N-terminal aminoacid, finger-print patterns following enzymatic or cyanogen bromide cleavage, as well as binding of estradiol-17 beta and tryptophan. Furthermore, an antiserum containing polyclonal antibodies to oSA showed perfect cross-reaction with oFF-I. Nevertheless, oFF-I is distinct and different from oSA, as would be evident from the data reported here. Of the two proteins, oFF-I alone is capable of suppressing pituitary FSH output in a dose dependent manner. Secondly, an antiserum containing polyclonal antibodies against Fraction-S2, a partially purified, biologically active fragment (M(r): 30-40 kDa) derived from oFF-I, cross-reacted with the 65 kDa inhibin, but did not recognize oSA. Finally, the CD-spectra of the two proteins, when examined as a function of pH, show characteristic differences. PMID- 1293027 TI - Kinetics of spermatogenesis in megachiropteran bat, Rousettus leschenaulti (Desmarset): seminiferous epithelial cycle, frequency of stages, spermatogonial renewal and germ cell degeneration. AB - The paper describes in detail the cytomorphology of different types of germ cells, the 10 typical cellular associations or stages of the cycle of seminiferous epithelium (CSE), frequency of appearance of these stages, pattern of spermatogonial stem cell renewal and per cent degeneration of various germ cells in R. leschenaulti. Of the 14 steps of spermiogenesis (stained with PAS haematoxylin) the first 10 were associated with the stages I-X, whereas, the remaining were found in association with one of the first six stages. The frequency of appearance of the various stages ranged from 3.84% (stage V) to 19.84% (stage I). These observations indicate that stage V is of shortest duration and stage I is of the longest duration in the bat. Five types of spermatogonia (A1, A2, A3, In and B) were identified based on their shape, size and nuclear morphology. Type A spermatogonia are oval with a large nucleus containing 1 or 2 nucleoli. The chromatin showed progressive condensation from A1 to A3 so that the latter appeared darkest among all the A type spermatogonia. The In type derived from A3 are smaller but appear darker than A3 due to heterochromatin crusts along the inner border of the nucleus. The B type spermatogonia derived from In are round and possess single nucleolus. The B type spermatogonia divided mitotically before entering meiosis or the actual production of the primary spermatocytes. The various spermatogonia divided mitotically at fixed stages of the cycle giving rise to their next generations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293028 TI - Amphiphilic and hydrophilic domains of human sperm membrane antigens recognized by immunoinfertile sera. AB - Selected sera from married couples with immunological infertility were used to identify antigens on hydrophilic and amphiphilic domains of human sperm membrane. Out of eight sera, six recognized proteins from the hydrophilic as well as amphiphilic regions of the sperm membrane. Sera were either reactive to acrosome or to equator and tail of human sperms in indirect immunofluorescence assay. PMID- 1293030 TI - Maturation-dependent goat epididymal sperm autoagglutination and its inhibition by a glycoprotein factor. AB - The maturing goat epididymal spermatozoa were isolated from different segments of epididymis and these cells dispersed in a modified Ringer's solution, were incubated at 37 degrees C for 60 min to evaluate their autoagglutination efficacy. Distal corpus-epididymal spermatozoa specifically showed high order of head-to-head autoagglutination property whereas all other sperm cells did not show any detectable aggregation. The goat epididymal plasma has been shown to possess an anti-agglutinin that markedly inhibits sperm agglutination phenomenon and also dissociates the cells from the sperm clusters. Epididymal plasma is the most potent source of the anti-agglutinin which is a heat-stable specific glycoprotein. Like the autoagglutination phenomenon, the initiation of sperm forward progression also starts in the distal-corpus epididymis. The temporal correlation of these two events suggests that sperm autoagglutination may be a prerequisite for the induction of flagellar motility during the epididymal maturity of male gametes. PMID- 1293029 TI - Antifertility investigations on the crude chloroform extract of Carica papaya Linn. seeds in male albino rats. AB - Crude chloroform extract of C. papaya seeds (5 mg/animal/day, po, for 20, 40 and 60 days) was investigated for contraceptive efficacy and related side effects in male albino rats. The crude extract reduced fertility to zero per cent by 40 to 60 days of treatment. Suppression of cauda epididymal sperm motility was the most pronounced effect of the drug administration. Scanning electron microscopic observations revealed treatment induced abnormalities in sperms. Cauda epididymal and testicular sperm counts decreased following treatment. Clinical parameters did not show any alterations. Results suggest that the contraceptive effects of chloroform extract of papaya seeds are mainly post-testicular in nature without influencing toxicological profile and libido of the animals. PMID- 1293031 TI - Effect of efferentiectomy on enzymes of glycolytic pathway, HMP pathway and TCA cycle in epididymis and vas deferens of rhesus monkey. AB - The importance of exocrine secretions of testis in the regulation of energy metabolism of the epididymis and vas deferens was examined in rhesus monkeys by performing efferentiectomy. At autopsy the epididymis was divided into initial segment, caput, corpus and cauda portions to make an account of regional differences, if any. Eleven enzymes of glycolysis, two key enzymes of HMP pathway and seven enzymes of TCA cycle were assayed in the epididymal segments and vas deferens of control (intact) and experimental (efferentiectomised for 90 days) monkeys. The results indicate that while anaerobic energy metabolism (glycolysis and HMP pathway) is sensitive to efferentiectomy chiefly in the proximal regions of epididymis, the oxidative pathway (TCA cycle) is dependent on testicular exocrine secretions throughout the length of epididymis, as well as in the vas deferens. Since all androgen-sensitive enzymes do not regress after efferentiectomy, it is suggested that unidentified exocrine factors of testis may have role in regulating energy metabolism in the epididymis and vas deferens. PMID- 1293032 TI - Role of prolactin on epididymal glycoprotein metabolism in matured monkeys, Macaca radiata: specific activities of glycosyltransferases and glycosidases. AB - Impact of altered serum prolactin status on enzymes involved in glycoprotein metabolism in epididymal tissue of matured monkeys was studied. Hyperprolactinemia (ovine prolactin-250 micrograms/kg body weight/day for 30 days) significantly inhibited the specific activities of dolichylphosphate mannosyl transferase, dolichylphosphate glucosyl transferase and galactosyl transferase, in the epididymal tissues. However, it had an enhanced effect on epididymal glycosidases such as beta-galactosidase, beta-N-acetyl glucosaminidase, beta-N-acetyl galactosaminidase, alpha-mannosidase and alpha-L fucosidase. Hypoprolactinemia (bromocriptine mesylate-1-mg/kg body weight/day for 30 days) on other hand had no significant effect on the specific activities of both, glycosyltransferases and glycosidases, in the epididymal tissues. The results suggest that hyperprolactinemia inhibits epididymal glycoprotein metabolism by impairing the incorporation of oligosaccharide units into proteins with enhanced degradation. This may have adverse effect on events leading to sperm maturation in epididymal environment. PMID- 1293033 TI - Serum and semen levels of immunoreactive prolactin, LH and FSH in normospermic, oligospermic and azoospermic men with obstructive infertility prior to and after vasoepididymostomy. AB - Attempts were made to validate RIA for prolactin (PRL), LH and FSH in semen from normospermic, oligospermic and azoospermic subjects. The RIA used to measure PRL and LH in semen fulfilled the criteria of reliability, whereas low levels of FSH in semen precluded the validation of FSH assay in semen. Semen levels of PRL and LH were significantly (P < 0.05) higher than serum levels in all groups of subjects investigated. Semen levels of FSH in azoospermic men after vasoepididymostomy (VEA), were significantly (P < 0.05) higher compared to azoospermic men prior to surgery. Serum levels of PRL were significantly higher (P < 0.05) in normospermic men compared to oligospermic and azoospermic men prior to and after surgery. Semen levels of PRL in normospermic men were comparable with oligospermic and azoospermic subjects prior to and after surgery. Serum levels of LH in oligospermic and azoospermic men who did not undergo surgery and in men reporting oligospermia after VEA were comparable to normospermic subjects but in men showing azoospermia post surgically, serum LH levels were significantly (P < 0.005) elevated. Semen levels of LH in men reporting azoospermia before surgery and in subjects showing oligospermia or azoospermia post surgically were significantly lower (P < 0.05) compared to men with normal sperm count. Serum levels of FSH were significantly elevated (P < 0.05) compared to semen levels in oligospermic men prior to surgery but this increase was not seen in post VEA subjects. These results were discussed. PMID- 1293034 TI - Effect of prolonged incubation of male rat whole pituitary or pituitary hypothalamus complex with testosterone on release of gonadotrophin and prolactin in vitro. AB - Investigations were undertaken to study the effect of in vitro addition of testosterone (0.3 mM) on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) by pituitary-hypothalamus complex (PHC) or the whole pituitary (PI) incubated for 72 hr, with incubation media changed every 24 hr. PHC or PI were from adult intact or castrated (7 days post castration) rats. The tissues incubated with or without testosterone were further exposed to 0.1 nM luteinizing hormone-releasing hormone (LHRH) for 4 hr. Incubation media and the pituitary were analyzed for PRL and gonadotrophin content. While PHC from normal and castrated rats released increasing amounts of LH with diminishing amounts of FSH and PRL at different periods of incubation, PI showed a decrease in the amounts of gonadotrophin and PRL released. Co-incubation of PHC or PI of intact or castrated rats with testosterone stimulated the release of LH and FSH during the first or second-24 hr incubation but inhibited the release of PRL in all the three incubations of 24 hr each. The extent of PRL inhibition increased with increasing incubation period. Testosterone had no effect on LHRH induced release of PRL but inhibited LHRH induced release of LH and FSH by pituitaries from constructs of normal rats. Testosterone reduced intrapituitary contents of PRL and FSH of intact and castrated rats. The data are interpreted to suggest that hypothalamus is essential for the maintenance of functional pituitary in vitro and that intrinsic differences exist in mechanisms regulating the secretion of LH, FSH and PRL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293035 TI - Immunoendocrine interrelationship--effect of ovariectomy on spleen and thymus in mouse. AB - Increase in the weights of spleen were observed 15 days after ovariectomy in adult as well as immature mice. However, no corresponding change was recorded in the splenocyte count. Morphological alterations in the shape of germinal centres was noted after ovariectomy in adult and immature mice. Increase in weight of the thymus could be demonstrated in adult mice only, with a concomitant enlargement of cortical and medullary region. PMID- 1293036 TI - Role of calcium in secretion of chorionic gonadotropin by first trimester human placenta. AB - The role of calcium in regulation of secretion of human chorionic gonadotropin (hCG) by first trimester human placental minces in vitro has been investigated. Depletion of calcium in the medium by addition of EGTA resulted in a drastic decrease in the levels of immunoreactive hCG in the medium with consequent of accumulation of hCG in the tissue. Addition of A 23187 which is a calcium ionophore resulted in a dose dose dependent increase in the hCG in the medium and this stimulatory response could not be observed in the absence of calcium. Use of lanthanum (a calcium antagonist) in place of calcium in the medium used resulted in a significant decrease in the levels of hCG in the medium. Addition of veratridine (a sodium channel activator) stimulated hCG secretion in a dose dependent manner. These results suggest that calcium is essential for normal secretion of hCG by human placenta. PMID- 1293037 TI - Early developmental studies with clomiphene citrate: their subsequent validation and extension. PMID- 1293038 TI - Vaccines for control of fertility. PMID- 1293039 TI - Early pregnancy factor. PMID- 1293040 TI - Mechanism of ovulation--an overview. PMID- 1293042 TI - Binding of radiolabelled luteinizing hormone to intact and ovariectomised rat uterus. AB - Binding of ovine LH to uterine tissue preparation from intact and ovariectomised rat clearly indicates that uterus possesses specific binding sites for LH. Binding characteristics of LH to uterine tissue preparation from intact rat showed saturability with high affinity and low capacity. Scatchard plot analysis showed dissociation constant of the specific binding site to be 0.12 x 10(-9) mol/l and the number of binding sites was 2.31 +/- 0.05 f mol/mg protein. Ovariectomy did not change the binding affinity but effected a decrease in the number of binding sites (1.7 +/- 0.08 f mol/mg protein). LH treatment of ovariectomized (ovx) rat had no effect on binding affinity but significantly increased the number of binding sites (3.23 +/- 0.1 f mol/mg protein). Reduction of uterine weight due to ovariectomy and marked increase of ovx rat uterine weight by LH administration indicate a source of estrogen in ovx rat. An in vitro uterine tissue slice (from intact and ovx rat) incubation showed depletion of 17 beta-estradiol (E2) content in ovx rat which significantly elevated on LH addition. Data suggest that LH binding to rat uterine tissue has biological relevance. PMID- 1293041 TI - Duration of antiestrogenecity of compound CDRI-85/287: a new orally active nonsteroidal antiimplantation agent. AB - Duration of antiestrogenic and antiimplantation action of CDRI-85/287, (2-(4-(2-N piperidino)ethoxy phenyl)-3-phenyl(2H)benzo(2)pyran), was studied in rat. Pretreatment of ovariectomized immature rats with this compound caused translocation of cytoplasmic estrogen receptor (ER) to the nucleus and a marked depletion of cytoplasmic ER pool resulting in a nonresponsive state of the uterus to subsequent estrogen administration until day 4. While in rats pretreated with estradiol, increased cytoplasmic ER level made the uterus responsive to a second injection of estrogen. In the delayed implantation model, 85/287 pretreated rats were given estrone on days 4, 5 or 6 post-antiestrogen treatment. No implantations were observed after estrone administration on day 4, but were present when estrone was given on days 5 or 6. Summation of these results suggests the duration of action of 85/287 to be 3-4 days in rat. PMID- 1293043 TI - Effect of fertility regulating agents on motility and zona-free hamster egg penetration by spermatozoa of bonnet monkey. AB - Administration of STS-557 (17 alpha-cyanomethyl-17 beta-hydroxyestra 4,9(10)-dien 3-one; 12 mg/monkey daily) for 4 weeks either alone or in combination with 20 Aet 1 (testosterone-trans-4-n-butyl cyclohexyl carboxylate; code CDB 1781; 40 mg/monkey single administration) had no significant effect on motility and zona free hamster egg penetration by spermatozoa of bonnet monkey, but continuation of the treatment for 12 weeks reduced (in one monkey treated with STS-557) or abolished (one treated with STS-557 and two with STS-557 + 20 Aet-1) the motility as well as zona-free hamster egg penetration (by spermatozoa of all treated monkeys). Motility and the ability to penetrate zona-free hamster egg returned to normalcy after 10 weeks of withdrawal of treatments. Active immunization of monkeys with ovine FSH (4 weeks after booster) had no adverse effect on motility of spermatozoa but none of the zona-free hamster eggs was fertilized. The correlation between motility and the capacity to penetrate the zona-free hamster eggs by monkey spermatozoa varies with the treatment. Such correlation was apparent in monkeys treated with STS-557 but not in monkeys immunized with ovine FSH. PMID- 1293044 TI - Ability of deglycosylated human chorionic gonadotropin (dghCG) to block luteal function and establishment of pregnancy in bonnet monkeys (Macaca radiata). AB - The ability of deglycosylated hCG (dghCG) prepared by deglycosylation of a clinical hCG (3000 IU/mg) preparation, to block luteal function during regular cycles as well as luteal rescue in simulated and mated cycles of female bonnet monkeys (M. radiata) has been evaluated. The cycle length (C:28 vs E:24 days) and the total progesterone produced during the luteal phase was significantly reduced (by 45%, P < .05) by injecting 450 micrograms of dghCG/day (in split doses) on days 18, 19, and 20 of cycle. At the doses tested the dghCG used did not exhibit any agonistic activity in the female monkey. In a second experiment injection of 200 micrograms of dghCG/day on days 18-20 of cycle blocked the normal response of the luteal tissue to exogenous hCG (10 micrograms of a 12,000 IU/mg preparation) injected on day 23 of cycle. In a third experiment no pregnancies occurred when a group of 5 animals were injected dghCG (450 micrograms dghCG/day) on days 18-21 of their mated cycle. Animals chosen for this study were proven fertile regularly cycling monkeys and these were cohabited with males between days 9 and 14 of cycle. Each of the monkeys was exposed to 3 consecutive treatment cycles. During post-treatment phase 2 out of 3 monkeys exposed to males became pregnant. The study clearly demonstrates that it is possible to block normal luteal function as well as luteal rescue of the female monkey by using dghCG in the right dose and mode. PMID- 1293045 TI - Contraceptive potential of an antiprogestin ZK 98.734: reversal of ZK 98.734- induced blockade of folliculogenesis with FSH and LH and their differential effects in bonnet monkeys. AB - Studies were undertaken in adult bonnet monkeys to investigate whether treatment with an antiprogestin ZK 98.734 at weekly intervals, starting from day one of menstrual cycle, could arrest ovulation and also to determine if ZK 98.734 induced blockade of ovulation could be reversed with gonadotropins. Adult animals have ovulatory menstrual cycles of normal duration were treated at weekly intervals with ZK 98.734 (25 mg/dose, sc, oil base) for 10 consecutive weeks and its effects on serum levels of estradiol, bioactive LH and progesterone, and endometrial histology were investigated. Following treatment with the antiprogestin they were treated with hMG or hFSH alone. Ovulation was blocked during treatment period in all the animals (n = 14). Typical follicular phase rise in estradiol levels was inhibited, mid cycle surge in the levels of bioactive LH was abolished and serum progesterone levels remained below 1 ng/ml throughout the treatment period. However, prolonged treatment had no significant effect on the basal levels of estradiol which were around 50 pg/ml. ZK 98.734 also had no significant effect on cortisol levels. In animals (n = 4) followed for recovery after the last dose, the treatment cycle length was increased to 117.8 + 6.8 days. In three animals the treatment cycles were anovulatory, whereas in one delayed ovulation with luteal insufficiency was observed. The endometrium had become atrophic. Treatment with hMG (Pergonal: 35 I.U. hLH and 35 I.U. hFSH) or hFSH (Metrodin, 35 I.U.) for 7 consecutive days initiated folliculogenesis and the animals ovulated either spontaneously or after a single im injection of hCG (100 I.U.) on day 8 in ZK 98.734 treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293046 TI - Manage of acute osteomyelitis in children--should it be conservative? AB - 73 children with acute osteomyelitis seen at King Fahd University Hospital, Al Khobar, Saudi Arabia were reviewed. Majority of patients were between the 6-10 year age group and male children predominated. All patients had incision and drainage and antibiotic therapy for a minimum of 6 weeks. Metaphysis of the tibia was the commonest site of infection and the staphylococcal species was cultured in 77% of children. Ampiclox was the most sensitive antibiotic. The average follow up was 4.9 years and the incidence of chronic osteomyelitis was 1.75%. In conclusion this study confirms that clinically it is not possible to detect a subperiosteal abscess within the first 48 hours. As blood culture is not 100% reliable in isolating the ineffective organism and incision and drainage plays a double role, firstly in the identification of the offending organism and secondly in the evacuation of pus. A six-week antibiotic therapy is essential to prevent any relapses. The correct management of acute osteomyelitis in children is surgical drainage of the affected site combined with antibiotic therapy. PMID- 1293047 TI - Serum electrolytes and osmolality in diabetes mellitus. AB - Fasting plasma glucose levels, serum osmolality and serum concentrations of sodium and potassium were determined in 73 Libyan diabetic patients attending the outpatient clinic of the Diabetes Hospital, Tripoli, Libya. The respective mean values were 234.8 +/- 9.7 mg.dl-1, 288.5 +/- 2 m0sm.L-1, 134.7 +/- 0.8 mEq.L-1 and 4.2 +/- 0.07 mEq.L-1. Statistically significant correlations were present between fasting plasma glucose and serum osmolality as well as the concentrations of serum sodium and potassium. There is is an increase in osmolality and levels of sodium and potassium concentration with an increase in plasma glucose concentration. PMID- 1293048 TI - High dose aerosol pentamidine for secondary Pneumocystis carinii pneumonia prophylaxis in AIDS patients. AB - In a prospective trial of aerosolized pentamidine as secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) 18 patients received 400 mg once weekly for a mean period of 15.5 months. Pentamidine aerosol was administered with an MA2 jet nebulizer. No PCP relapses were observed and no serious side effects occurred. PMID- 1293049 TI - Cerebrospinal fluid neopterin and beta 2-microglobulin levels in neurologically asymptomatic HIV-infected patients before and after initiation of zidovudine treatment. AB - The effect of zidovudine on beta 2-microglobulin and neopterin in the cerebrospinal fluid (CSF) was studied in ten HIV-seropositive neurologically healthy individuals. CSF concentrations of neopterin decreased by 53% (from 20.3 to 9.5 nmol/l, p < 0.01) and beta 2-microglobulin by 36% (from 2.8 to 1.8 mg/l, p < 0.01) four to eight months after initiation of therapy. PMID- 1293050 TI - Transintestinal elimination of ciprofloxacin in humans--concomitant assessment of its metabolites in serum, ileum and colon. AB - Ciprofloxacin (200 mg) was infused to seven patients at the beginning of elective colorectal surgery. Thirty minutes after the end of infusion (i.e. 60 min after the start of the operation) ciprofloxacin reached concentrations of 1.60 mg/l in serum and of 3.42-6.07 mg/kg fresh weight in the ileum and colon. During the next 30 min (90 min after the start of operation) the concentration of ciprofloxacin in serum decreased to 86% of its initial level, but this decrease was less rapid than that observed in the ileal (to 56.8%) or colonic (to 74.8%) mucosa. Three metabolites could be identified (desethylen-, sulpho-, oxociprofloxacin). Initially, at 60 min the amount of these metabolites was about 15% of the total drug concentration in serum, but only 2-3% of that in the gut tissues. At 90 min the relative amount of metabolites was increased in serum as well as in the gut tissues. It is concluded that transintestinal elimination of ciprofloxacin is a general feature of the whole gut. Obviously, the elimination process is not due to degradation of ciprofloxacin within the gut wall. PMID- 1293051 TI - Risk factors of HIV-1 infection among female prostitutes in Khon Kaen, Northeast Thailand. AB - HIV infection has increased to epidemic proportions in Thailand since 1987. There have been separate epidemics among population groups at high risk of infection and significant increases in different localities. The northeast region of Thailand has been affected by the epidemic since early 1989. The purpose of this study was to identify factors associated with HIV transmission among prostitutes during an early phase of the epidemic in the regional center of Khon Kaen. Three hundred and fifty-six prostitutes known to work in the urban area of Khon Kaen (Ampur Muang) in November 1990 were included in the study. Prostitutes were divided into two groups according to the type of place where they worked: direct prostitutes (in brothels, n = 217) and indirect prostitutes (in massage parlors, n = 139). The prevalence of HIV infection was found to be 12% among direct prostitutes and 2% among indirect prostitutes. Four variables were significantly associated with HIV infection after adjusting for confounders by logistic regression analysis: previous work in an area of high HIV prevalence, working in Khon Kaen less than one month, a low price charged for sex and using injectable contraceptives. Follow-up investigations are currently being carried out to explore in detail the association between the use of injectable contraceptives and HIV infection. PMID- 1293053 TI - Hepatosplenic candidiasis, a fatal disease? AB - We report on two patients with acute leukemia and prolonged granulocytopenia after cytotoxic therapy in whom the diagnosis hepatosplenic candidiasis was made. Both patients developed upper abdominal discomfort with elevated alkaline phosphatase after resolution of granulocytopenia. The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography. Both patients were initially treated with amphotericin B i.v., one of them received liposomal amphotericin B (cumulative dose of 2,530 mg and 570 mg, respectively). Thereafter, therapy was continued for months with oral fluconazole. The treatment of hepatosplenic candidiasis was successful, however, the patients died from relapse and progression of leukemia. PMID- 1293052 TI - Carriage of methicillin-resistant Staphylococcus aureus by non-hospitalized subjects in Israel. AB - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the anterior nares and axilla was studied in 920 non-hospitalized subjects: 350 drug addicts, 350 individuals presenting at a hospital emergency room for various reasons, and 220 hospital health care workers. S. aureus was isolated from 105 (11.4%) subjects, in six (6.3%) of whom the isolates were methicillin-resistant. The isolation rate of the organism and the prevalence of resistant strains in the different subgroups were, respectively: drug-addicts, n = 32 (9.1%), n = 2 (6.9%); emergency room patients, n = 36 (10.2%), n = 1 (3.2%); and hospital health care workers, n = 37 (16.8%), n = 3 (8.5%). Our findings suggest that MRSA remains uncommon in the community, while the prevalence of S. aureus carriage (including methicillin-resistant strains) in hospital personnel is quite similar in divergent geographical areas. PMID- 1293054 TI - Resistance of recent Neisseria gonorrhoeae isolates in Nigeria and outcome of single-dose treatment with ciprofloxacin. AB - One hundred four patients (71 males, 33 females) with acute gonococcal urethritis or cervicitis were treated with a single oral 250 mg dose of ciprofloxacin at Jos University Teaching Hospital, Jos, Nigeria. All gonococcal strains were isolated from appropriate pre-treatment swabs. Penicillinase-producing Neisseria gonorrhoeae (PPNG) accounted for 72.8% of all isolates. In vitro sensitivity of gonococcal isolates to ciprofloxacin was 100%, while that to penicillin, ampicillin and co-trimoxazole was below 15%. Of the 104 patients treated with ciprofloxacin, 73 (70%) attended a follow-up visit. Seventy-three (100%) patients showed clinical cure and elimination of N. gonorrhoeae from the respective site of infection. Post-gonococcal urethritis or cervicitis believed to be due to concomitant chlamydial infection was found in 22 (30.1%) patients--18 males and four females. No adverse reactions were reported by any patient. Our findings show that a single oral dose of ciprofloxacin (250 mg) is well tolerated and effective in the treatment of uncomplicated gonorrhoea and is particularly useful in regions with a high prevalence of PPNG. PMID- 1293055 TI - Active immunization with pC protein of Borrelia burgdorferi protects gerbils against B. burgdorferi infection. AB - Serious infection due to Borrelia burgdorferi and the disseminated infection characteristic of the disease possess unique treatment problems. The wide and still increasing incidence of Lyme borreliosis as well as the problems in treatment call for effective prevention strategies by active immunization. Vaccination experiments were done to determine if active immunization of gerbils with recombinant OspA and pC protects against infection with strains of B. burgdorferi. Gerbils were vaccinated with recombinant OspA and pC (20 kDa protein) and challenged four weeks later with a clone (derived from B. burgdorferi strain PKo) which expresses an abundant amount of pC but only little OspA. Non-immunized gerbils challenged with the same B. burgdorferi strain were used as controls. Both groups of immunized gerbils developed antibodies against the recombinant vaccines. The pC vaccinated group was protected against infection, whereas the OspA vaccinated group showed signs of infection. The non vaccinated group developed generalised infection. These results show that pC should be considered as a further vaccine candidate and probably needs to be combined with OspA for an efficient vaccine against B. burgdorferi. PMID- 1293056 TI - Intracellular bactericidal activity of fosfomycin against staphylococci: a comparison with other antibiotics. AB - The intracellular bactericidal activity of fosfomycin was compared to that of other anti-staphylococcal agents. Two staphylococcal strains (one isolate of Staphylococcus aureus and one isolate of Staphylococcus epidermidis) were incubated in vitro with human granulocytes isolated from volunteers. After phagocytosis and removal of residual extracellular bacteria, the cells were resuspended in the presence of clinically relevant concentrations of fosfomycin, teicoplanin, vancomycin and rifampin. The number of bacteria surviving intracellularly was determined by colony counts after osmotic lysis of the granulocytes at different time intervals. Incubation with fosfomycin resulted in a mean reduction of intracellular bacteria by approximately two logs of ten within 18 h for both staphylococcal strains. Although less effective than rifampin, fosfomycin showed a significantly higher intracellular activity than the glycopeptide antibiotics in this model. PMID- 1293057 TI - The non-enzymatic inactivation of thirteen beta-lactam antibiotics in human faeces. AB - In order to obtain a method that could predict the in vitro inactivation of an antibiotic in the digestive tract, the non-enzymatic inactivation of 13 beta lactam antibiotics by human faeces was investigated. Benzylpenicillin, amoxicillin, amoxicillin/clavulanate, cloxacillin, piperacillin, temocillin, cefuroxime, cefamandole, cephradine, cefotaxime, ceftazidime, aztreonam and imipenem were mixed in six graded concentrations with faecal suspensions of 30 healthy volunteers. After incubation the remaining antimicrobial activity was measured by means of a serial dilution method. A relationship between the initial antibiotic concentration (Aia) and the remaining antimicrobial activity after incubation (Asd) was derived, namely: Asd = 1/2[(Aia-K-F)+square root ((Aia-K-F)2 + 4 K Aia)]. The parameters K and F represent the intrinsic dissociation constant and the amount of available bindingsites in the faeces, respectively. Asd values were predicted with a reasonable degree of accuracy for all thirteen antibiotics. Dissociation constants differed significantly between the penicillins and the cephalosporins but F- values did not differ between cephalosporins and penicillins. PMID- 1293058 TI - The effect of liposomal cefoperazone against Pseudomonas aeruginosa in a granulocytopenic mouse model of acute lung infection. AB - The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host. PMID- 1293059 TI - Successful treatment of brain abscess caused by Nocardia in an immunocompromised patient after failure of co-trimoxazole. AB - Disseminated infection caused by Nocardia asteroides is a fairly rare entity occurring mostly in immunocompromised states. Metastatic brain abscesses are a frequent and ominous complication. We report on a patient whose underlying disease was stage II pulmonary sarcoidosis. He acquired disseminated N. asteroides infection while on immunosuppressive therapy with prednisolone. After the generally recommended therapy with co-trimoxazole (trimethoprim/sulfamethoxazole) proved ineffective in controlling his brain abscesses, the lesions of the central nervous system completely resolved under a combination of oral rifampicin with i.v. imipenem, followed by oral rifampicin and ampicillin/clavulanic acid. PMID- 1293060 TI - Pseudomonas vesicularis bacteraemia. AB - A case of repeated episodes of Pseudomonas vesicularis bacteraemia, in a 54-year old woman with a past history including systemic lupus erythematosus and chronic active autoimmune hepatitis is reported. She was treated with tobramycin and ceftazidime but bacteraemia persisted until surgical resection of the infected tissue was performed. PMID- 1293061 TI - Elevated levels of interleukin 6 in serum of patients with serious group A streptococcal infections. PMID- 1293062 TI - Illness behavior in children of chronic pain patients. AB - OBJECTIVE: Recent studies on pain behavior have pointed to a relationship between expression of illness in patients with chronic pain and reports of physical complaints in other family members. This article includes two related studies. The aim of the first study was to determine whether, among pain patient families, parents who exhibited higher levels of illness behavior and emotional distress were more likely to report that their children had frequent pain complaints. The aim of the second study was to assess whether children of patients with chronic pain were perceived by their parents to have more pain and illness behavior than children of non-pain parents. METHOD: In the first study, forty-two primary caregivers in families with a parent with chronic pain completed questionnaires regarding their children's pain and illness behavior. In the second study, report of somatic complaints in children of chronic pain parents was compared to complaints in fifty-five children of parents without chronic pain. RESULTS: Results of the first study showed that frequently reported pain in the child was associated with significantly higher levels of parent disability, pain behavior and emotional distress. Results of the second study showed that children of patients with chronic pain were reported to have more frequent abdominal pain and to use more medication than children of parents without pain. CONCLUSIONS: The findings of these studies suggest that children of parents with chronic pain may be at risk for illness behavior, especially when the parents exhibit emotional reactions to their pain. PMID- 1293063 TI - Munchausen syndrome by proxy. AB - This study examined the indicators of possible presence of Munchausen Syndrome by Proxy (MSBP) in pediatric inpatients discharged against-medical-advice (AMA), in cases transferred to another hospital, and in regular discharges. In a two-year period, there were fourteen AMA discharges and twenty-four transfer cases. These were compared to a randomly selected sample of forty-one regular discharges occurring during the same time period, matched for age, sex and pediatric service. The records were scored for the presence or absence of six MSBP characteristics, which had been developed from a review of MSBP literature. The findings indicated a suspicion for MSBP in 64 percent of the AMA cases, 8 percent of the transfer cases, and none in regular discharges. The findings suggest that AMA discharges need to be examined for the possible presence of MSBP. PMID- 1293064 TI - Paramenstrual aggression in mentally retarded adult ameliorated by buspirone. AB - OBJECTIVE: This case examined the efficacy of buspirone therapy as a reductive technique for severe treatment resistant paramenstrual aggression. METHOD: Aggressive outbursts of an institutionalized mentally retarded adult were analyzed and correlated with menstrual cycling. Behavior was closely monitored, and after ineffective trials of antipsychotics, benzodiazepines and beta blockers, a trial of buspirone was initiated. RESULTS: Buspirone therapy resulted in a marked decrease in aggressive incidences, and substantial increases in desirable behaviors. As a result of the subjects improvement, doses of concurrent psychotropic medications were reduced or discontinued altogether. CONCLUSIONS: The authors conclude that buspirone is an effective pharmacotherapy for paramenstrual aggression in the developmentally disabled, and encourage similar experimentation when behavior seems to be otherwise untreatable. PMID- 1293065 TI - A review of the postconcussion syndrome. AB - OBJECTIVE: This review will focus on aspects of the postconcussion syndrome (PCS), including accompanying symptomatology, neuropsychological changes, brain imaging studies and treatment. METHOD: In each topic area, those research studies resulting in the most interpretable data are reported. Since there is little research in some aspects of the PCS, some studies of limited merit are described, with their limitations outlined, in lieu of not reporting any study. The section on psychopharmacology largely consists of opinions of recognized clinicians, since there is almost no research on the psychopharmacology of PCS. RESULTS: Mild traumatic brain injury is a relatively frequent occurrence which often results in the postconcussion syndrome (PCS), consisting of complaints of irritability, fatigue, headache, difficulty concentrating, dizziness, and memory problems. Anxiety and depression are also frequently present, especially later in its course. Although the PCS has often been thought to reflect a psychological response to injury, there is considerable recent evidence to suggest that it is primarily a physiologic disturbance. For most individuals, treatment consists primarily of education of the patient and his/her family, along with supportive counseling regarding emerging problems at work or at home. A subgroup of patients, however, may require psychopharmacologic intervention. CONCLUSION: More research is needed in all aspects of PCS, especially its neurophysiology and pharmacologic treatment. Relationships between neurophysiological changes and behavioral and neuropsychological changes are unknown. New imaging techniques, such as single-photon emission tomography, and positron emission tomography will likely play an important role in understanding the physiology of this disorder. PMID- 1293067 TI - Transmission studies with simian immunodeficiency virus of macaques; persistent infection of baboons. AB - The host range of SIVmac was investigated in three monkey species. Blood-borne and cell-adapted virus inocula obtained from a rhesus macaque infected with SIVmac251 were compared. African green monkeys were not susceptible to infection, whereas baboons and rhesus macaques became persistently infected and showed similar patterns of seroconversion. However, in contrast to the macaques, no clinical or histopathological evidence of disease was seen in the baboons 2 years after virus inoculation. Thus baboons could be used as an alternative to macaques in vaccine development studies with this particular isolate of SIVmac. Furthermore, this system may be useful for the investigation of factors responsible for disease progression. PMID- 1293066 TI - Monoclonal antibodies recognising pol and env proteins of mammalian retroviruses. AB - Mouse monoclonal antibodies were generated for three 20- to 23-mer synthetic peptides whose amino acid sequences were highly conserved in the pol or env regions of 14 mammalian and two avian retroviruses. By Western-blot analysis, these antibodies recognised the epitopes in major and minor pol or env proteins of six mammalian type-C and -D retroviruses. One of the anti-env monoclonal antibodies was found to recognise all the env transmembrane proteins of six mammalian retroviruses examined. PMID- 1293068 TI - Experience with subfascial ligation for varicose veins in Tanzania: a brief communication. AB - From January 1987 through December 1989, ten patients with varicose veins complicated by postphlebitic ulcers were treated at Muhimbili Medical Center, Tanzania, by subfascial ligation of perforating veins. The technique employed was a posterior subfascial approach which avoids making the skin incision through the ulcer itself. The follow up periods ranged from one to three years and there was no recurrence of the ulcer in any of the patients in the study. The major indication for performing the procedure was the presence of a varicose stasis ulcer. Before surgery, all patients had a complete peripheral vascular examination to exclude deep venous thrombosis. Healing of varicose ulcers and elimination of stasis eczema had to be achieved four weeks before surgery. The authors maintain that patients who present with varicose veins of the lower leg and a postphlebitic stasis ulceration invariably have incompetence of the valves in the perforating veins and should be treated by subfascial ligation of the perforating veins. PMID- 1293069 TI - Estimation of the urinary galactitol level in children by capillary gas chromatography. AB - A rapid and efficient capillary gas chromatography was utilized to measure urinary galactitol in 133 non-galactosemic children on a free diet. The children aged from 12 days to 14 years were divided by age into six groups. The urinary galactitol concentration was found to be the highest (64.04 mmol/mol creatinine) in the neonatal group and the lowest (7.12 mmol/mol creatinine) in the group over 2 years old. It is concluded that the urinary concentration of galactitol is strongly age-dependent. PMID- 1293070 TI - Helicobacter pylori infection and gastroduodenal disease: a comparison of endoscopic findings, histology, and urease test data. AB - To determine the prevalence and significance of Helicobacter pylori (H. pylori) infection, biopsies of the antral mucosa were obtained from 139 patients and 43 asymptomatic volunteers. The specimens were examined by hematoxylin-eosin staining and the ureas test. The detection rate of H. pylori by histologic examination was 91.3% in patients with duodenal ulcer, 75.0% in those with combined duodenal and gastric ulcer, 63.6% in those with gastric ulcer, 22.9% in those with gastric carcinoma, 36.4% in those with gastric adenoma, 14.3% in those with gastric hyperplastic polyp, and 51.7% in those with gastritis, and the respective percentages detected by the urease test were 91.3%, 75.0%, 54.5%, 28.6%, 27.3%, 14.3%, and 44.8%. H. pylori was also detected in 10/43 (23.3%) asymptomatic healthy volunteers by histology and the urease test. The prevalence of H. pylori was significantly higher in the patients than in the asymptomatic healthy volunteers (p < 0.05). H. pylori was detected in 62.9% of patients with endoscopic erosive gastritis and in 97.9% of those with histologically proven chronic active gastritis. The urease test was positive in 77/82 patients who were histologically positive for the organism (sensitivity: 93.9%), and it was negative in 98/100 patients who were negative by histology (specificity: 98.0%). Thus, there was over 90% agreement between the urease test and histology. Our investigations showed that H. pylori was closely related to peptic ulcers and antral gastritis, and that the urease test provides a simple, rapid and accurate diagnosis of H. pylori infection. PMID- 1293071 TI - Cellular aging and expression of fibronectin. AB - Several changes in the functional characteristics of fibronectin (FN) have been noted as cells become senescent in culture. In a previous report we showed that the steady state level of FN mRNA increases significantly during the process of in vitro cellular aging in a fibroblast strain. Because a phenomenon observed in one cell strain may not be the case in other cell strains, we extended the previous study and confirmed that this is a common phenomenon in at least two fibroblast strains of different origin. The greatest change in the proportion of cells expressing high levels of FN occurs near the end of a culture's proliferative potential. The proportion of cells unable to synthesize DNA follows a similar pattern. We also found that increasing cell size correlates closely with higher levels of FN expression. Thus, there is a clear correlation between increased FN mRNA content and in vitro cellular senescence. In order to see if this phenomenon could also be observed in cells aged in vivo, we analyzed cells aged in vivo. We found that fibroblasts from donors of higher age show lower labeling index, express a higher level of FN and come to have a larger cell area, similar to cells aged in vitro. This strongly suggests that a fibroblast in vivo ages with aging of the individual in like manner to that observed in in vitro aging cells, that is, by exhausting division potential. This supports studies using in vitro aging cells as a model for cellular aging in vivo. PMID- 1293072 TI - Light and electron microscopic observation in a case of congenital renal proximal tubular dysfunction. AB - We report a case of congenital renal proximal tubular dysfunction (CRPTD) accompanied by IgA nephropathy. The mesangial matrix was slightly increased with depositions of IgA and C3. Podocytes contained many clear vacuoles. Cuboidal cells, as well as squamous cells, lined the parietal epithelium of Bowman's capsule, although the functional or pathological significance of the cuboidal cells is unknown. The proximal tubular cells appeared to have a less-developed apical endocytic complex, basal infoldings and fewer lysosomes. These morphological changes may reflect proximal tubular dysfunction. PMID- 1293073 TI - Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. II. Isolation of arbekacin-resistant strain. AB - Resistance patterns against 24 antimicrobial agents were examined for 50 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital during the period October 1990 and July 1991. Overall resistance (the percentage of highly and moderately resistant strains) to the antimicrobial agents is summarized as follows: methicillin 100%, flomoxef 100% (beta-lactams); kanamycin 94%, tobramycin 94%, amikacin 100%, isepamicin 94%, gentamicin 80%, dibekacin 94%, arbekacin 2% (basic oligosaccharide group/aminocyclitols); ofloxacin 96%, temafloxacin 96%, levofloxacin 96% (fluoroquinolones); erythromycin 98%, clarithromycin 98%, josamycin 30% (macrolides); vancomycin 0% (glycopeptide); tetracycline 94%, minocycline 94% (tetracyclines); fosfomycin 100%; mikamycin B 30%, nosiheptide 0% (peptide); rifampicin 2% (ansamycin); streptomycin 2% (basic oligosaccharide group); chloramphenicol 2%. Arbekacin resistance was observed in one case: the cross resistance was complete among the aminocyclitol antibiotics tested in this study and streptomycin, probably due to the ribosomal alteration. PMID- 1293074 TI - Elastosis in breast--correlation with epithelial proliferation in benign disease and carcinomatous growth. AB - Elastosis in the breast is an unusual phenomenon and its morphogenesis has not yet been fully ascertained. The degree of elastosis in the breast associated with benign diseases, including fibroadenoma and fibrocystic disease as well as with breast carcinoma, was examined with special reference to the correlation between the degree of epithelial proliferation and elastosis. Using the immunohistochemical method, the presence of elastase (EL) and alpha 1 antichymotrypsin (ACT), one of the protease inhibitors, in these epithelial cells was also investigated to elucidate the role of an imbalance in these enzymes in the morphogenesis of the elastosis. Consequently, it was shown that there is a tendency in fibroadenoma and fibrocystic disease, for epithelial proliferation to be related to the degree of elastosis, and that the lack of EL in proliferated epithelial cells might play a role in the occurrence of elastosis, although ACT has no significant correlation. On the contrary, in our study noninvasive carcinoma showed marked periductal elastosis but no stromal elastosis, while invasive carcinoma showed various degrees of periductal and stromal elastosis. In invasive carcinoma, especially scirrhous carcinoma, the degree of ACT in cancer cells correlated well with stromal elastosis, although there was no correlation with EL. These findings suggest that an imbalance of the protease-antiprotease system, produced by epithelial cells of the breast, contribute to the morphogenesis of elastosis, although the physiological event, aging, is only marginally related to elastosis. Further investigation of the cells producing elastin and regulatory factors may be necessary. PMID- 1293075 TI - Fate of ciliated epidermal cells during early development of Xenopus laevis using whole-mount immunostaining with an antibody against chondroitin 6-sulfate proteoglycan and anti-tubulin: transdifferentiation or metaplasia of amphibian epidermis. AB - Xenopus embryonic epidermis changes its cellular composition during development: the appearance of ciliated epidermal cells before hatching is a remarkable characteristic. In this study, the functional change of ciliated cells to mucus secreting cells was examined with immunocytochemistry using anti-tubulin and anti chondroitin 6-sulfate (C6S). Before hatching, most epidermal cells were labeled with anti-C6S in a granular fashion. Immunoelectron microscopy revealed that the anti-C6S-positive structure was the mucus granule. Ciliated epidermal cells lacked anti-C6S staining, but were strongly labeled with anti-tubulin. After hatching, most ciliated cells in the surface of the embryo disappeared. During their disappearance, some ciliated cells exhibited anti-C6S-positive granular labeling. This strongly suggests that the disappearance of ciliated cells is a functional conversion to mucus-secreting cells instead of shedding through cell death. PMID- 1293076 TI - Expression of intestinal alkaline phosphatase in human organs. AB - Human intestinal alkaline phosphatase was immunohistochemically identified and localized in the pancreas, liver and kidney by use of a monoclonal antibody specific for intestinal alkaline phosphatase isozyme and by amplified biotin streptavidin staining. In all the examined organs, the intestinal isozyme was found to be localized in the epithelial cells of ducts: bile ducts in the liver, distal convoluted tubules and collecting tubules in the kidney and ducts in the secretory epithelium in the pancreas. In the liver the antibody also stained some sinus-lining cells. In all the examined organs the endothelial cells of the capillaries and some vessels were stained. By use of immunoelectron microscopy, intestinal alkaline phosphatase was, as expected, found to be localized to the microvillar region of the small intestine. The isozyme was abundantly expressed in the apical area of the microvilli and in membrane remnants in the fuzzy coat. Capillaries and vessels in the submucosa were also stained, as well as small vesicles in the endothelial cells. The present investigation demonstrates the expression and localization of the intestinal alkaline phosphatase in several organs, though previously believed to be expressed only in the intestine. PMID- 1293077 TI - Lectin binding sites on head structures of the spermatid and spermatozoon of the mosquito Culex quinquefasciatus (Diptera, Culicidae). AB - The presence of intranuclear and acrosomal lectin binding sites in spermatids and spermatozoa of the mosquito Culex quinquefasciatus was analysed. Direct and indirect lectin-gold techniques were used on LR White-embedded cells. The nuclear compartment was the structure most intensely labelled. Early spermatid nucleus showed moderate labelling for peanut agglutinin (PNA), Griffonia simplicifolia IB4 (GS-IB4) and Ricinus communis agglutinin (RCA), and light labelling for the other lectins tested. The sperm nucleus was intensely labelled by all lectins. The acrosome, an enzyme-containing structure, was labelled by some lectins. The anterior acrosomal region was labelled by PNA, while the proximal acrosomal region was labelled by PNA and G. simplicifolia II (GS II) lectins, and showed the presence of fucose residues with the use of Ulex europaeus I (UEA-I) lectin. The spermatozoa stored in the spermatheca showed the same pattern of labelling as that observed in spermatozoa localized in testis and seminal vesicles for all lectins tested. Carbohydrate residues in the nuclear compartment may be involved with the process of chromatin condensation. In the acrosomal region these residues may play a role in the process of sperm-oocyte interaction. PMID- 1293078 TI - Protein kinase C (alpha, beta, gamma) in Pacinian corpuscle. AB - Immunocytochemical demonstration of protein kinase C (PKC) subspecies (alpha, beta, gamma) was carried out in Pacinian corpuscles of rat hind feet using monoclonal or polyclonal antibodies against each of these subspecies. The inner core cells and lamellae and the Schwann cell cytoplasm of the nerve fiber innervating the corpuscle were strongly positive for PKC alpha-immunoreactivity (IR). In contrast, the axon terminal and the outer core did not display any positive alpha-IR. Very weak PKC beta-IR was detected in the ultraterminal region of the axon terminal, while the trunk region showed no immunoreactivity. Very faint PKC beta-IR was found also in the lamellar cells located at the periphery of the inner core and the endoneurial fibroblasts in the intermediate layer. PKC gamma-IR was not detected in any part of the corpuscle. The strong PKC alpha-IR in the inner core and the presence or absence of PKC alpha-, beta-, and gamma-IR in the axon terminal are discussed from the point of view of the functional aspects of each part. PMID- 1293079 TI - Glycosaminoglycans and fibrillar collagen in Priapulida: a histo- and cytochemical study. AB - The distribution of glycosaminoglycans and fibrillar collagen was studied in various tissues of priapulids, which represent an ancient group of marine metazoa. Sulphated glycosaminoglycans, as demonstrated at the electron microscopical level by Cupromeronic blue, were predominantly found in the cuticle, in basement membranes and also in the narrow connective tissue space below epidermis and anterior intestine. On the basis of their morphology the Cupromeronic blue precipitates could be divided into several groups. Fibrillar collagen occurred in the connective tissue under the epidermis and the epithelium of the anterior intestine. The spatial interrelationship between fibrillar collagen and glycosaminoglycans lacked with some exceptions, the high regularity found in connective tissues of other invertebrates and of vertebrates. This might be related to the special skeletal system of priapulids, consisting mainly of a strong extracellular cuticle and the turgor of the fluid-filled body cavity. In such a system the usual supportive structures seem to be of less functional significance. PMID- 1293080 TI - Use of a murine T-cell hybridoma expressing human T-cell receptor alpha- and beta gene products as a tool for the production of human T-cell receptor-specific monoclonal antibodies. AB - We describe the production of mouse monoclonal antibodies specific for the human TcR using as the immunogen transfected murine T-cell hybridoma cells coexpressing mouse CD3 with human Jurkat TcR alpha and beta chains. The shortage of monoclonal antibodies (mAbs) specific for the human TcR-V alpha and V beta families reflects the difficulties in their production by conventional methods using whole human T cells or purified soluble receptors as immunogens. As an alternative strategy to circumvent these difficulties, we have generated a transfected mouse T-cell line expressing a human (Jurkat) TcR alpha beta dimer in a complex with mouse CD3. The parental mouse T-cell line, TG40, is a cell surface TcR-negative, cytoplasmic CD3 positive variant of the mouse T-cell hybridoma 2B4. The human-TcR alpha beta expressing mouse transfectant was used to immunize mice with the same genetic background as the parent mouse T-cell line, and a human TcR-specific response was successfully achieved. MAb-producing hybridomas were generated by fusing spleen cells from the immunized mice with the mouse myeloma cell line NSO. Of 124 hybridoma supernatants screens, 72 showed reactivity to the human T-cell line Jurkat. Twenty-four of the hybridomas producing human (Jurkat) TcR-specific antibodies were cloned and screened for reactivity to Jurkat TcR. Several IgG2b and IgM mAbs specific for the Jurkat T cell line were selected on the basis of their ability to modulate surface CD3 expression on Jurkat cells. Most of the antibodies do not stain other TcR-expressing human T cell leukemia cell lines, implying specificity for the variable domains of the Jurkat TcR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293081 TI - Evaluation of an automated method of percent reactive antibody determination. AB - A fluorescence-based automated method of percent reactive antibody (PRA) analysis is described. This method utilizes the conventional antibody-mediated, C' dependent lymphocyte microcytotoxicity assay to detect alloantibodies, but replaces the eosin-based method for detection of cell death with a fluorescence based method. To identify viable cells, lymphocytes were pretreated with carboxy fluorescein diacetate (CFDA), which fluoresces green, to identify viable cells. To identify dead cells after the reaction with antibody and C', they were treated with propidium iodide (PI), which fluoresces red. Pretreatment of lymphocytes with CFDA did not affect their ability or interact with alloantibodies in the microcytotoxicity assays. When visually analyzed, detection of cell death by fluorescence was as sensitive as detection by eosin exclusion. However electronic detection of fluorescence was slightly more sensitive than visual detection. Automation of the fluorescent method required a calculation that converts electronic data to an ASHI score for cell death. One such method is described and evaluated. Both the automated and the conventional methods of analysis were used to obtain PRA values for various sera. There was good correlation between the PRA values obtained with the automated method versus the conventional method. Further, there was good correlation for PRA-derived alloantibody specificities obtained with the automated method versus the conventional method. These data demonstrate that automated fluorescence-based PRA analysis is an effective and practical alternative to conventional PRA analysis. PMID- 1293082 TI - HLA-DR and -DQ genotypes of celiac disease patients serologically typed to be non DR3 or non-DR5/7. AB - The susceptibility to develop celiac disease (CD) seems to be primarily associated to a particular HLA-DQ alpha/beta heterodimer encoded by the DQA1*0501 and DQB1*0201 alleles, in cis position on the DR3-DQ2 haplotype or in trans position by DR5-DQ7/DR7-DQ2 heterozygotes. However, exceptional patients exist who are neither DR3 nor DR5/DR7, particularly among Southern European populations. We therefore examined the DRB1, DQA1, and DQB1 alleles of 13 Spanish CD patients who were serologically typed to be neither DR3 nor DR5/DR7. Five patients were found to carry the DQA1*0501 and DQB1*0201 alleles either in cis or in trans position, three of them had previously been serologically mistyped. However, two of these patients carried DQA1*0501 and DQB1*0201 on haplotypes other than DR3 or DR5 in combination with DR7. One of the latter patients carried an unusual DR4-DQ2 haplotype, while another had an unusual DR8-DQ2 haplotype. Four of the remaining eight patients carried DR4-DQ8 haplotypes. Taken together, our findings provide further evidence that the DQ alpha/beta heterodimer encoded by the DQA1*0501 and the DQB1*0201 alleles confers the primary HLA-associated susceptibility to develop CD. However, our studies also corroborate that a second (and "weaker") HLA-associated CD susceptibility gene may be present on some DR4 carrying haplotypes. PMID- 1293083 TI - HLA and immunoglobulin polymorphisms in idiopathic dilated cardiomyopathy. AB - Dilated cardiomyopathy (DCM) is an idiopathic heart muscle disorder. The presence of circulating cardiac antibodies and the association with HLA-DR4 are consistent with autoimmune pathogenesis in a subset of patients. Sixty-eight DCM patients and 277 controls were typed for IgG heavy-chain constant region (Gm) and kappa light-chain (Km) allotypes. All patients and 210 of the 277 controls were HLA-DR typed. The Gm (1, 3, 17; 23; 5*, 21, 28) phenotype was overrepresented in DCM compared with controls (25% vs 13%, p = 0.0139, pc = NS, RR = 2.23). The frequency of this phenotype was higher in patients with younger age at onset, shorter symptom duration, and among those who were positive for cardiac as well as for non-organ-specific autoantibodies than in controls. A higher frequency of the Gm (1, +/- 2, 3, 17; +/- 23; 5*, 21, 28) heterozygous phenotypes was also found in DCM compared to controls (40.91% vs 26.89%; p = 0.02, pc = 0.04, RR = 1.88). The finding of Gm heterozygosity in DCM was associated with serum positivity for cardiac antibodies. A higher proportion of DCM patients were positive for both the Gm (1, 3, 17; 23; 5*, 21, 28) phenotype and HLA-DR4 compared to normals (3/68 vs 0/210; p = 0.04, RR = 22.50).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293084 TI - Comparative studies of isolated CD3: CD8, CD3: CD3, and monovalent CD3 binding on CD8+ T-cell activation: model of progressive T-cell receptor aggregation synergism. AB - The TCR and CD8 complexes of CD8+ T cells bind to different regions of MHC class I molecules and both play important roles in the response of the CD8+ T cells to Ag/MHC on APCs. In this report, we mimicked common MHC binding with an anti CD3:anti-CD8 (CD3,8) BSMAB to isolate the effect of CD3: CD8 pairing, compared this with the effect of CD3: CD3 pairing by the parental bivalent anti-CD3 MAB, and with monovalent anti-CD3 binding by an anti-CD3: anti-CD4 (CD3,4) BSMAB. CD3: CD8 pairing induced an increase in cytosolic free [Ca2+] 1.5 to 3.0-fold greater than the increase induced by CD3: CD3 pairing whereas monovalent CD3 binding induced only 20%-30% of the increase. Postbinding receptor migration studies suggested that microaggregation increased from monovalent CD3 binding to CD3: CD3 pairing to CD3: CD8 pairing. Further studies revealed that progressively higher concentrations of antibodies were needed from CD3,8 to CD3,3 to CD3,4 to initiate the same degree of DNA synthesis. These results demonstrated that Ti/CD3 and CD8 can indeed be bridged by a single molecule. A model of direct CD8: CD3 synergism was raised as a possible explanation for the enhanced activation induced by CD3: CD8 pairing. The observed parallel between all three parameters and the number of TCRs that can be directly linked by the Abs raised a nonmutually exclusive model whereby CD3 binding induces activated TCR intermediaries (aTCRi) that progressively synergize with other adjacent aTCRis. In this model, this dominant inter-aTCRi synergism may be enhanced by the di- and multimeric CD8 alpha chains serving as aTCRi-aggregation foci. PMID- 1293085 TI - HLA polymorphism in a Mataco South American Indian tribe: serology of class I and II antigens. Molecular analysis of class II polymorphic variants. AB - In the present study, HLA-A, B, C, DR, DQ, and DP loci were analyzed in a group of Mataco Amerindians of Argentina. Using reagents from the 11th International Histocompatibility Workshop (11th IHW), class I specifities such as Bw70, Bw75, and Bw48 were found in this population, other than the HLA determinants commonly described in South American Indians. The class II antigens found were DR4, DRw14, and DRw8 at the DR locus, and DQw4 and DQw7 at the DQ locus. The analysis of DRB1 DR4 related alleles, performed by PCR amplification and oligonucleotide probe hybridization, showed the presence of DRB1*0403, *0404, *0405, and *0411 in individuals from this ethnic group. By the analysis of DRB1-DRw14 related alleles, two variants were found: DRB1*1402 and DRB1*1406, the latter provisionally called DRB1 14.6 in 11th IHW. The DRw8-related allele present was DRB1*0802. The analysis of DRB3 gene revealed only the presence of DRB3*0101 allele in DRw14 individuals. DPB1 locus was also analyzed in unrelated individuals of the same population. Only five DPB1 alleles were found: DPB1*0201, *0301, *0402, *0501, and *1301 over the 19 previously described in the literature. These findings emphasize the restricted HLA class I and II variation observed in this ethnic group as it has been previously shown in other American groups. Some particular haplotypes in this Mataco tribe are described in this work. PMID- 1293086 TI - Generic HLA-DRB1 gene oligotyping by a nonradioactive reverse dot-blot methodology. AB - HLA-DRB1 allelic specificities can be determined using SSOs annealing to their complementary PCR-amplified target DNA. To perform HLA-DR oligotyping routinely for donors and recipients of bone marrow transplantation, a "reverse" dot-blot technique has been developed that consists in the hybridization of labeled PCR amplified target DNA to SSOs that have been first attached to nitrocellulose membranes. The 15 oligonucleotides chosen enabled the following HLA-DRB1 "generic" specificities to be defined: DR1, BON, 2, 3, 4, 11, 11 JVM, 12, 13, 13 HAG, 14, 7, 8, 9, 10. The genomic DNA was amplified by asymetric PCR with incorporation of biotinylated deoxynucleotides predominantly to generate labeled single-stranded DNA. Hybridization between specific immobilized oligoprobes and target DNA was nonradioactively detected by a colorimetric reaction using alkaline phosphatase. The reverse dot-blot methodology was successfully tested, first, for the determination of HLA-DR4 subspecificities, and then the procedure was routinely applied to the generic HLA-DR oligotyping of bone-marrow donors and recipients. PMID- 1293087 TI - Cytotoxic and proliferative allospecific T-cell clones contain perforin and mediate anti-CD3-induced cytotoxicity. AB - Some in vitro-generated allospecific T-cell clones can kill target cells bearing specific antigen, whereas others can only proliferate in response to that antigen. The mechanism of target lysis by clones that exhibit antigen-specific cytotoxicity is thought to involve the exocytosis of lytic granules, which contain the pore-forming protein perforin. Here, CD4+, CD8+, and CD4-8- T-cell clones, positive for CD3 and the alpha/beta T-cell receptor, were tested for their ability to lyse the mouse-anti-human CD3 hybridoma OKT3; this hybridoma has been shown to trigger the cytolytic mechanism in cytotoxic T cells regardless of their clonal specificity. We found that all in vitro-generated allospecific T cell clones can efficiently lyse the OKT3 targets whether or not they can kill alloantigen-bearing lymphoblastoid B-cell line targets. Furthermore, all tested clones contained perforin. The OKT3 hybridoma was not lysed by perforin-negative, CD3+ leukemic T-cell lines or by CD3- NK clones. Thus, the presence of perforin in T-cell clones correlated with their ability to lyse OKT3 targets, but not with their ability to lyse alloantigen-bearing targets. These results demonstrate that T-cell clones that are nonlytic when activated by specific antigen nevertheless contain a complete lytic mechanism and also support the proposed central role in perforin in that mechanism. PMID- 1293088 TI - Congenital 21-hydroxylase deficiency as a new deletion mutation. Detection in a proband during subsequent prenatal diagnosis by HLA typing and DNA analysis. AB - A child with 21-OH-def whose 9 weeks' pregnant mother was referred for prenatal diagnosis was found upon very careful histocompatibility testing to lack expression of any of his father's HLA antigens on his peripheral blood lymphocytes. The possibility of alternative paternity was considered to be extremely unlikely after additional genetic marker tests. The conclusion that the affected child's disease resulted from inheritance of a maternal CYP21B (21-OH) deletion and a de novo deletion in the paternal chromosome 6 segment that includes both the CYP21B (21-OH) and HLA genes was confirmed by subsequent DNA analysis using 21-OH, C4, DPB, and PCH6 probes. The presence of a heterozygous RFLP for DPB, the absence of a deletion for either CYP21B (21-OH) or C4 genes, and the presence of a paternal HLA antigen haplotype on the fetal cells additionally indicated that the fetus lacked the same deletion and could be predicted to be completely normal. PMID- 1293089 TI - Conservation of genes encoding HLA-B5 and B35 cross-reactive group antigens in various races. AB - HLA-B5 and B35 CREG antigens include HLA-B35, B51, B52, B53, and B78. Recent studies suggest that the genes encoding the HLA-B5, B35 CREG, and HLA-B58 antigens share a common ancestor. We sequenced the exons of the genes encoding HLA-B51, B53, and B58 from American black individuals and the gene HLA-B52 encoding from an Arabic individual, and compared them with previously reported sequences of HLA-B51 (B*5101) and HLA-B52 (B*5201) from Japanese, HLA-B53 (B*5301) from an Algerian, and HLA-B58 (B*5801) from a Sardinian. The sequences of the genes from the American black and Arabic individuals were identical to those from the other races. These findings support the hypothesis that these antigens have evolved prior to divergence of the major ethnic groups. PMID- 1293090 TI - High yields of anti-HLA human monoclonal antibodies can be provided by SCID mice. AB - In an attempt to develop a suitable model for increasing the yield of human anti HLA mAbs, we have used mice with SCID for i.p. injection of two human-mouse heterohybridomas. HMP1 hybridoma secretes a DQB1*0201 allele-specific human mAb whereas HMP12 secretes a human mAb recognizing the DRB1*1101, 1102, 1103, and 1104 alleles. Both hybridomas could be grown in SCID mice as localized tumors with no apparent alteration in the morphology of the cells or in the immunoglobulin secretion. Ascitic fluid was produced that showed a 600- to 1000 fold increase in monoclonal antibody cytotoxic titer as compared with that obtained in tissue culture. HLA-DQB1* and DRB1* alleles recognized by ascites and supernatants from SCID-derived cultures were analyzed by microlymphocytotoxicity assay on a small panel of B-lymphoblastoid cell lines. The results show that HLA specificity was retained after in vivo passage. PMID- 1293091 TI - Evaluation of students and new graduates. PMID- 1293092 TI - Viral infections in joints. PMID- 1293093 TI - Questions theory on cause of exercise-induced pulmonary hemorrhage. PMID- 1293094 TI - Metabolic acidosis and ionized calcium. PMID- 1293095 TI - World AIDS Day 1992--how veterinarians are helping. PMID- 1293096 TI - Pets prove therapeutic for people with AIDS. PMID- 1293097 TI - Encountering AIDS--a personal perspective. PMID- 1293098 TI - Study explores health risks and the human/animal bond. PMID- 1293100 TI - Immunodeficiency syndrome makes cats desirable HIV research model. PMID- 1293099 TI - Essex reveals new gene therapy for AIDS. PMID- 1293101 TI - Veterinarian with HIV infection shares views. PMID- 1293102 TI - Veterinarian writes musical tribute for AIDS victims. PMID- 1293103 TI - Shielding clients from injury protects against malpractice claims. PMID- 1293105 TI - Employment, starting salaries, and educational indebtedness of 1992 graduates of US veterinary medical colleges. PMID- 1293104 TI - The veterinarian's role in the AIDS crisis. PMID- 1293106 TI - Pursuing good moral character. PMID- 1293107 TI - A seeker of the truth. PMID- 1293108 TI - Diet-induced alterations of lipoprotein metabolism. PMID- 1293109 TI - Difficult dermatologic diagnosis. PMID- 1293110 TI - Transfusion practices and costs in dogs. AB - A geographically stratified sample of 25 small-animal practices administering at least six transfusions to dogs over the last 12 months was surveyed to determine how veterinarians obtain blood for transfusions, the direct costs of administering transfusions, and the impact of available blood on the management of critically ill dogs. The primary source of donor blood for each practice was a borrowed dog (12 practices) or in-house dogs kept on the premises (12 practices). Only one practice obtained blood from a nearby veterinary school. There was a wide variation in practices regarding testing for diseases and screening of donors. Thirty-six percent of practices surveyed did not screen dogs for infectious diseases or evaluate hematologic variables prior to blood donation. Twenty-four percent of the respondents evaluated the donors solely for the purposes of detecting microfilaria. The remaining 40% of the practices performed one or more of the tests generally recommended as part of a screening program for potential blood donors. The blood type of donors was determined in eight of the practices, whereas blood typing of recipients was not routinely performed. Ten of 25 practices performed blood crossmatches, but only one practice performed crossmatches in all cases. The distribution of direct costs per whole blood transfusion (500-ml unit) ranged from 25 to more than $300, with three fourths of the practices having costs less than $100. The higher-cost practices were those that maintained donors on the premises specifically for blood donation purposes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293111 TI - Investigation of an outbreak of velogenic viscerotropic Newcastle disease in pet birds in Michigan, Indiana, Illinois, and Texas. AB - An outbreak of velogenic viscerotropic Newcastle disease in exotic pet birds in the United States from April through July 1991 was investigated. More than 2,000 pet birds in 5 states (Michigan, Indiana, Illinois, Texas, and Maryland) were tested. Infected birds were found in Michigan, Illinois, Indiana, and Texas. This disease was eradicated without spread to domestic poultry. Epidemiologic investigations revealed the source of infection to be double yellow-headed Amazon parrots suspected to be illegally imported into Texas. PMID- 1293112 TI - Serum thyroid hormone concentrations and thyrotropin responsiveness in dogs with generalized dermatologic disease. AB - Fifty-eight dogs with generalized dermatologic disease that had not been given glucocorticoids systemically or topically within 6 weeks of entering the study were evaluated for thyroid function by use of the thyrotropin-response test. Dogs were classified as euthyroid or hypothyroid on the basis of test results and response to thyroid hormone replacement therapy. Baseline serum thyroxine (T4), free T4 (fT4), and triiodothyronine (T3) concentrations were evaluated in the 58 dogs. Serum T4, fT4, and T3 concentrations were evaluated in 200 healthy dogs to establish normal values. Hormone concentrations were considered low if they were less than the mean -2 SD of the values for control dogs. Specificity of T4 and fT4 concentrations was 100% in predicting hypothyroidism; none of the euthyroid dogs with generalized skin disease had baseline serum T4 or fT4 concentration in the low range. Sensitivity was better for fT4 (89%) than for T4 (44%) concentration. Significant difference was not observed in serum T4 and fT4 concentrations between euthyroid dogs with generalized skin disease and healthy control dogs without skin disease. Serum T3 concentration was not accurate in predicting thyroid function; most of the euthyroid and hypothyroid dogs with skin disease had serum T3 concentration within the normal range. PMID- 1293113 TI - Comparison of computed tomography and radiography for detecting changes induced by malignant nasal neoplasia in dogs. AB - The ability of computed tomography and radiography to detect changes associated with nasal neoplasia was compared in dogs. Eighteen areas or anatomic structures were evaluated in 21 dogs for changes indicative of neoplasia. Computed tomography was superior (P < or = 0.05) to radiography for detecting changes in 14 of 18 areas. Radiography was not superior for detecting changes in any structure or area. Computed tomography reveals vital information not always detected radiographically to assist in providing a prognosis and in planning treatment for nasal neoplasms in dogs. PMID- 1293114 TI - Characteristics of pet populations and households in the Purdue Comparative Oncology Program catchment area, 1988. AB - A 1-stage, random-digit dial telephone survey was conducted to obtain information on characteristics of pet populations and pet-owning households in 1988 in Marion and Tippecanoe Counties, Indiana. Interviews for 653 out of 731 eligible households were completed (response rate, 88%). Approximately half of the households in each county owned a pet. Of these, 35% owned at least 1 dog, and 23% owned at least 1 cat. Households with pets were more likely to be larger and have a higher median income score than were households without pets. Households with children between 6 and 17 years old were more likely to own pets than were households with no children; however, no difference in pet ownership proportions was determined for households with children < or = 5 years old, compared with households without children. For dogs, younger dogs and male dogs were less likely to have been neutered than older dogs and female dogs. Older cats were more likely to have been neutered than younger cats, with neutering percentages of > 90% for cats in the oldest age group. Approximately 20% of dogs and 40% of cats had not been seen by a veterinarian in the 12 months preceding the interview. PMID- 1293115 TI - Serum haptoglobin concentration in swine naturally or experimentally infected with Actinobacillus pleuropneumoniae. AB - Serum haptoglobin (Hp) concentrations were measured in swine that were naturally or experimentally infected with Actinobacillus pleuropneumoniae. In swine from a specific-pathogen-free herd, mean serum concentration of Hp (+/- SD) was 5.79 +/- 1.06 mg of cyanmethemoglobin-binding capacity (CHBC)/dl. Serum Hp concentrations in paired samples were measured at 7-day intervals in 40 swine randomly selected from a conventional herd that was experiencing an acute episode of pneumonia and deaths caused by A pleuropneumoniae serotype-5 infection. Day-0 and -7 serum Hp concentrations were 24.58 +/- 1.38 and 23.10 +/- 1.12 mg of CHBC/dl, respectively, with no significant difference between these measurements. In a second conventional herd with a history of chronic infection with A pleuropneumoniae serotype 5, serum concentrations of Hp measured in paired samples obtained 6 days apart were 12.36 +/- 0.81 and 18.63 +/- 0.76 mg of CHBC/dl, respectively, and were significantly (P < 0.05) different from each other. Twenty-nine 12-week-old conventional swine were challenged intranasally with A pleuropneumoniae serotype 1 (n = 19) and serotype 5 (n = 10). Serum Hp concentration increased from prechallenge concentrations of 7.49 +/- 1.38 and 15.10 +/- 1.22 mg of CHBC/dl, respectively, to 41.01 +/- 1.35 and 22.37 +/- 1.78 mg of CHBC/dl, respectively, 72 hours after challenge. For these 29 swine, serum Hp concentration was positively correlated with rectal temperature (r = 0.34; P < 0.001) during the immediate postchallenge period. PMID- 1293116 TI - Gastric perforation associated with administration of ibuprofen in a dog. AB - A 3-year-old Chow Chow was examined because of a 2-week history of vomiting and anorexia after administration of 200 mg of ibuprofen. Peritoneal effusion and free gas within the peritoneal cavity were observed on radiography of the abdomen. A full-thickness perforation of the pyloric antrum and pylorus were detected during exploratory laparotomy, and a Billroth-I gastroduodenostomy was performed successfully. PMID- 1293117 TI - Chronic diarrhea associated with intestinal anomalies in a six-year-old dog. AB - A 6-year-old mixed-breed dog was referred because of chronic diarrhea, which had begun after antibiotic treatment for pulmonary disease. Intestinal bacterial overgrowth was presumptively diagnosed on the basis of intestinal mucosal cytologic examination and low serum cobalamin concentration. When the diarrhea did not respond to treatment, contrast radiography was performed and a short small intestine was found. The diarrhea could not be managed by medical treatment, and the dog was euthanatized. Necropsy revealed 2 blind intestinal pouches attached to a 46-cm length of small intestine connecting the stomach and colon. The dog's deteriorating condition was attributable to necrosis and rupture of 1 of the pouches. PMID- 1293118 TI - Thrombocytopenia associated with administration of trimethoprim/sulfadiazine in a dog. AB - A diagnosis of trimethoprim/sulfadiazine-induced, immune-mediated thrombocytopenia in a dog was made, using a novel in vitro assay for thrombolytic activity. The assay quantifies thrombolytic activity by measuring the amount of platelet fragments in normal canine platelets before and after incubation with plasma from the thrombocytopenic dog. This report confirms previous reports of the development of thrombocytopenia after administration of trimethoprim/sulfadiazine, and describes a new assay that, after further validation, may be useful in the diagnosis of immune-mediated thrombocytopenia when an adequate sample of platelets cannot be obtained for quantification of platelet-associated IgG. PMID- 1293119 TI - Obstructive enterolith in an 11-month-old miniature horse. AB - An obstructive enterolith was diagnosed in an 11-month-old 68-kg miniature horse with a 24-hour history of mild, intermittent colic. Abdominal radiography revealed gas distention of the cecum and the right and left ascending colon, and a radiodense elliptical structure in the area of the left kidney. During exploratory laparotomy, the right dorsal colon was noticed to contain ecchymotic hemorrhage and generalized discoloration in the portion proximal to the location of the enterolith. While exteriorizing the ascending colon, it ruptured caudal to the diaphragmatic flexure in the right dorsal colon. Radiography of the enterolith did not reveal a metallic center, but division of the stone allowed identification of a canvas cloth, and chemical analysis determined the stone's composition to be ammonium magnesium phosphate. Although equine enteroliths were reported over 100 years ago and the factors involved in their formation were investigated, the reasons for their development have yet to be determined. The mean reported age of horses requiring abdominal surgery because of an obstructive enterolith is 10 years, with the youngest being 4 years. The time required for an enterolith to enlarge is unknown, although a true enterolith has not been reported in horses younger than 4 years of age. PMID- 1293120 TI - Calcifying tendinopathy of the biceps brachii in a dog. AB - Calcifying tendinopathy of the biceps brachii was associated with lameness in a 1.5-year-old Rottweiler. Lameness was relieved by excision of the calcified mass and suture repair of the partially ruptured tendon. Calcifying tendinopathy is not well described in dogs, but it is a recognized clinical syndrome in human beings. The etiopathogenesis of the condition in human beings and dogs is poorly understood. Wider recognition of calcifying tendinopathy in dogs should lead to a better understanding of the disease and development of appropriate clinical treatments. PMID- 1293121 TI - Results of surgical management of portosystemic shunts in dogs: 20 cases (1985 1990). AB - Serum bile acid (SBA) values were obtained in 20 dogs, 2.5 to 60 months (mean, 18.6 months) after surgery for occlusion of a congenital portosystemic shunt. The SBA values obtained after food was withheld were significantly (P < 0.005) reduced at follow-up, compared with preoperative values. In 85% of the dogs (17/20), response to surgery was graded by the owners as excellent or good, although most dogs had abnormal SBA values at follow-up. Significant difference in clinical results or follow-up SBA values was not found in dogs that had complete or partial occlusion of the shunting vessel. Correlation between clinical results and SBA values also was not detected. Dogs that were > 2 years old at the time of diagnosis and surgery had a significantly (P = 0.012) poorer clinical result than that of dogs < 1 year old. PMID- 1293122 TI - Evaluation of risk factors for blastomycosis in dogs: 857 cases (1980-1990) AB - An epidemiologic study was conducted by use of the Veterinary Medical Data Base to investigate risk factors for blastomycosis in dogs. From January 1980 through June 1990, 971 cases of blastomycosis in dogs from 22 North American veterinary teaching hospitals were identified. Of these cases, 114 (11.7%) were excluded from the study because of incomplete information regarding age, body weight, sex, and neuter status. A control group of 417,079 dogs was selected that included all other dogs with medical conditions unrelated to blastomycosis for which records were submitted to the data base during the same period. The prevalence of blastomycosis in dogs was 205/100,000 admissions during the study period. When veterinary teaching hospitals were grouped on the basis of their general geographic location, dogs in the East South central, East North central, West South central, and South Atlantic regions had a significantly (P < 0.05) increased risk of acquiring blastomycosis, compared with that of dogs in the Mountain/Pacific region. When teaching hospitals from all geographic regions were considered, dogs had a significantly (P < 0.05) increased risk of acquiring blastomycosis in autumn, compared with that in spring. Sporting dogs and hounds, as defined by the American Kennel Club, were at increased risk for blastomycosis. At highest risk were Bluetick Coonhounds, Treeing-walker Coonhounds, Pointers, and Weimaraners, compared with mixed-breed dogs. Ages of dogs with blastomycosis tended to be normally distributed. Generally, the highest-risk group was composed of sexually intact male dogs, 2 to 4 years old, weighing 22.7 to 34.1 kg. This same pattern was observed for sporting dogs and hounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293123 TI - Traumatic luxation of the cubital joint (elbow) in dogs: 44 cases (1978-1988). AB - The medical records from 44 dogs with traumatic luxation of the cubital joint were reviewed. Closed reduction was performed in 35 dogs, and open reduction in 9 dogs. Excellent or good results were achieved in 31 of 35 dogs (88.6%) treated by closed reduction and in 5 of 9 dogs (55.6%) treated by open reduction. Collateral ligament repair, performed in 5 dogs, did not appear to affect the prognosis. Factors such as body weight and type and duration of external coaptation also did not appear to influence the outcome. Increased dysfunction associated with open reduction most likely was caused by the chronic nature of the dislocation, iatrogenic damage to the articular cartilage during reduction, or both. A good prognosis for return to normal function with minimal gait abnormality can be expected in most cases of traumatic luxation of the cubital joint treated by early closed reduction. PMID- 1293124 TI - Flavobacterium indologenes infection in leopard frogs. AB - An investigation of an epidemic of infectious disease in a frog (Rana pipiens) colony was conducted. Six of 40 frogs in a continuous (once through) water flow housing system had weight loss, swollen abdomen, corneal edema, uveitis, subcutaneous edema, petechial hemorrhage, incoordination, and respiratory distress. The frogs had lesions consistent with bacterial septicemia. A gram negative, nonfermenting bacillus, Flavobacterium indologenes (Flavobacterium sp biovar IIb), was isolated in pure culture from tissues and blood. The clinical isolate was used to inoculate healthy frogs sc. An isolate identical to the one isolated from the sick frogs was recovered from tissues and blood of the inoculated frogs. Inoculation of the housing water in a nonflow-through system did not result in disease, despite proliferation of the Flavobacterium spp in the water; therefore, it is likely that establishment of infection requires the presence of the organism in sufficient numbers and a portal of entry into the body. PMID- 1293125 TI - Perineal hernia in a cougar. AB - An 8-week-old female cougar with a history of acute perineal swelling was determined to have a perineal hernia. The hernia was repaired with the conventional suture technique. This case represents an unusual perineal hernia, which may have been congenital. PMID- 1293126 TI - What is your diagnosis? Cranial abdominal hernia. PMID- 1293127 TI - Androgen regulation of programmed death of normal and malignant prostatic cells. AB - Androgen-dependent normal prostatic glandular cells and androgen-dependent prostatic cancer cells can be induced to undergo cell death after androgen ablation. This death does not require the cells to proliferate and occurs as an energy-dependent process collectively referred to as "programmed cell death" in which the cells actively commit "suicide." Associated with this programmed cell death pathway is the enhanced expression of a series of genes and the fragmentation of the genomic DNA into nucleosomal oligomers. This genomic DNA fragmentation is the irreversible commitment step in the death of the cell and results from activation of Ca2+/Mg(2+)-dependent endonuclease activity within the cell nucleus. This activation is due to sustained elevation of intracellular free Ca2+ (Cai) induced after androgen ablation. Metastatic prostatic cancer within an individual patient is heterogeneous, including both androgen-dependent and independent cancer cells. Thus, androgen ablation is rarely curative since it only induces the programmed death of the androgen-dependent cancer cells without activating this pathway in the androgen-independent cancer cells within the patient. Androgen-independent prostatic cancer cells do not activate this death process after androgen ablation, since this does not induce a sustained increase in Cai. A new approach to treat androgen-independent prostatic cancer cells has focused on the use of chemotherapeutic agents to induce a sustained increase in Cai. These studies demonstrate that if such a sustained elevation in Cai is maintained, even androgen-independent prostatic cancer cells undergo programmed cell death. PMID- 1293129 TI - Role of nerve growth factor-like protein in the paracrine regulation of prostate growth. AB - Prostate cancer is the most commonly diagnosed form of malignant neoplasia in men. Considerable evidence has accumulated suggesting that paracrine interactions between stromal cells and epithelial cells mediate, in part, the growth and development of the prostate. A nerve growth factor-like protein secreted by stromal cells has been implicated in the paracrine regulation of prostate epithelial tumor cell growth in vitro. This prostate-derived nerve growth factor like protein differs from the known members of the neurotrophin family of proteins, and may represent a prostate-specific form of this family of gene products. Furthermore, corresponding nerve growth factor receptors have been localized to the epithelial cells of the human prostate in vivo, consistent with a role of the receptors and the adjacent nerve growth factor-like protein secreted by stromal cells, in the paracrine regulation of prostate growth and neoplasia. PMID- 1293128 TI - Normal and abnormal development of the male urogenital tract. Role of androgens, mesenchymal-epithelial interactions, and growth factors. AB - Androgen-dependent male urogenital development occurs via mesenchymal-epithelial interactions in which mesenchyme induces epithelial morphogenesis, regulates epithelial proliferation, and evokes expression of tissue-specific secretory proteins. Mesenchymal-epithelial interactions continue to be important into adulthood. For example, mesenchyme of the urogenital sinus (UGM) and seminal vesicle (SVM) induce dramatic morphologic and functional changes in various adult epithelia. Since adult epithelial cells are unquestionably responsive to mesenchymes that can elicit expression of alternative morphologic and functional phenotypes, established carcinomas might also be influenced by their connective tissue environment. In this regard, Dunning prostatic tumor has been induced by UGM or SVM to differentiate into tall columnar secretory epithelial cells. This change in cytodifferentiation is associated with a reduction in growth rate and loss of tumorigenesis. The role of soluble growth factors in the mechanism of mesenchymal-epithelial interactions is discussed. PMID- 1293130 TI - Acute and long-term effects of a single dose of the fungicide carbendazim (methyl 2-benzimidazole carbamate) on the male reproductive system in the rat. AB - The effects of carbendazim (methyl 2-benzimidazole carbamate) on the testis, efferent ductules, and sperm were determined in the adult rat after a single oral dose. Two experimental trials were performed: a time response between 2 hours and 32 days after exposure using 0 and 400 mg/kg, and a dose response at 2 and 70 days after exposure using 0 to 800 mg/kg doses. In experiment 1, effects were seen throughout the 32-day period, beginning 8 hours after exposure; the effects included first an increase in testis weight, then decreases in testicular spermatid numbers and in the percentage of morphologically normal cauda sperm. In experiment 2, significant testicular and efferent ductal alterations occurred in animals treated with doses of 100 mg/kg or greater. A dose-dependent increase in testicular weight 2 days after treatment was accompanied by increases in seminiferous tubular diameter and excessive loss of immature germ cells in a stage-dependent manner. There was also a dose-dependent increased incidence of occlusions in the efferent ductules. The occluded ductules were characterized by severe inflammation and exhibited disorganization of the epithelium. At 70 days, there were dose-dependent decreases in mean testis weight and mean seminiferous tubular diameter; however, only minimal long-term effects were seen at 50 mg/kg. In testes exhibiting seminiferous tubular atrophy of greater than 25% (100 mg/kg or greater doses), all of the testes were associated with efferent ductules containing occlusions. Caput sperm numbers were significantly reduced in these testes. Occlusions, abnormal ductules, fibrosis, spermatic granulomas, and mineralization were observed in the ductuli efferents. Long-term effects of carbendazim on the testis were induced primarily by ductal occlusions. Results show that carbendazim produces more severe short- and long-term effects on the male reproductive system than the fungicide benomyl. PMID- 1293131 TI - Effect of fucoidin on human sperm-zona pellucida interactions. AB - The authors recently reported that fucoidin (a polymer of predominantly L-fucose sulfate) produced a strong, significant, and dose-dependent inhibition of sperm zona binding under hemizona assay conditions. The current studies were designed to evaluate the mechanisms underlying this inhibitory activity. Using computerized semen analysis, the monoclonal anti-sperm antibody T-6 and indirect immunofluorescence technique, and the fura-2 indicator, no significant impact of fucoidin on sperm motion parameters, on the spontaneous acrosome reaction, or its prerequisite, the increase in calcium influx, were observed. Subsequently, a mild acid hydrolysis of the fucoidin molecule was performed, followed by sizing hydrolysates in a Biogel P2 column and separating fractions (n = 6). All fucoidin fragments significantly inhibited tight binding of human sperm to human zona pellucida under hemizona assay conditions (range, 56%-94%) when tested individually. These results provide further evidence that the effect of fucoidin is produced by a receptor-ligand association. PMID- 1293132 TI - Differential regulation in the release of bioactive versus immunoactive gonadotropins from cultured rat pituitary cells by inhibin and androgens. AB - Using in vitro bioassays and radioimmunoassays, the authors examined the interactions between purified 32kD ovine inhibin, testosterone, and dihydrotestosterone on basal and GnRH-stimulated secretion of gonadotropins in primary rat pituitary cell cultures. This study demonstrates that inhibin and androgens: 1) differentially regulate gonadotropin levels, 2) cause changes in the amounts of bioactive and immunoactive FSH and LH released. In conclusion, differences in bio- and immuno-FSH and LH secretion suggest that the endocrine milieu results in not only quantitative but qualitative changes in the secreted gonadotropin isoforms. PMID- 1293133 TI - Androgen-induced prevention of the outgrowth of cranial gonadal suspensory ligaments in fetal rats. AB - Normal and disturbed testicular descent is frequently approached exclusively through a consideration of the caudal testicular suspensory apparatus. This is surprising, because embryonal gonads develop with both cranial and caudal suspensory ligaments, and the sexes differ with respect to the persistence and development of both the cranial and the caudal ligaments. The current study examined the possible role of fetal testicular androgens in male-specific failure of the development of the cranial gonadal suspensory apparatus in rats. Normal male fetuses were studied, as well as fetuses exposed to the anti-androgen flutamide from day 10 after conception. Females were given daily injections of methyl-testosterone alone or in combination with the anti-androgen cyproterone acetate from day 15 after conception, and were studied on day 22. The cranial ligaments remained of minor extension in normal males but developed considerably in females. They developed in female fashion in males exposed to flutamide, and persisted throughout postnatal life. Cranial ligaments did not develop in females that had been exposed to methyl-testosterone. Simultaneous treatment with a large dose of cyproterone acetate effectively counteracted this effect. Fetal testicular testosterone thus appears to play a key role in the prevention of the outgrowth of the cranial gonadal/genital ligament in rats. The supposed function of this suspensory apparatus makes it likely that its persistence in males, as the consequence of inappropriate androgen action during fetal life, facilitates disturbance of testicular descent. This finding may contribute to understanding developmental disorders underlying disturbed testis descent in humans. PMID- 1293134 TI - Dose-response effects of gonadotropin-releasing hormone on plasma concentrations of gonadotropins and testosterone in fertile and subfertile stallions. AB - Five fertile and five subfertile stallions were treated with a single intravenous injection of saline the first week followed by a single intravenous injection of varying doses of gonadotropin-releasing hormone (5, 10, 25, 100, 500 micrograms) given in a randomized fashion over the next 5 weeks during the nonbreeding season. Blood samples were collected periodically before and after treatment for analysis of luteinizing hormone, follicle stimulating hormone, and testosterone content by radioimmunoassay. Before treatment, semen samples were collected every other day for 3 weeks for analysis of volume, concentration, motility, pH, and morphology. Basal plasma levels of luteinizing hormone were higher (P < 0.05) in the subfertile group, follicle stimulating hormone levels tended to be higher (P < 0.10) in the subfertile group, and testosterone levels were similar in the two groups. A significant linear-log dose-response relationship was observed for plasma luteinizing hormone (P < 0.05) and follicle stimulating hormone (P < 0.05) to exogenous gonadotropin-releasing hormone in both the fertile and subfertile group. A linear-log dose-response relationship was also observed for plasma testosterone (P < 0.05) in the fertile group. The magnitude of the luteinizing hormone and follicle stimulating hormone response to gonadotropin-releasing hormone across doses was similar in both groups of stallions. A significant testosterone response to gonadotropin-releasing hormone in the subfertile group of stallions was not observed (P > 0.05). Mean testosterone concentrations after treatment in terms of net increase and percent of baseline were significantly lower (P < 0.05) in the subfertile group compared to the fertile group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293135 TI - Ultrastructure of adult and juvenile marmoset (Callithrix jacchus) Sertoli cells in vivo and in vitro. AB - The morphologic differentiation of Sertoli cells isolated from adult and juvenile marmosets and cultured on different extracellular matrices was evaluated by light and electron microscopy and compared to cells in vivo. Both cell types could be maintained in culture for at least 6 days. The degree of cellular differentiation, shape, ultrastructural appearance, and polarity seemed to benefit from laminin-coated substrata, compared with collagen-, fibronectin-, serum-, and heparan sulfate-coated substrata. With the former two substrates, a difference in behavior between juvenile and adult cells was evident. Whereas juvenile cells displayed a lesser degree of differentiation, adult cells exhibited identical morphologic characteristics in culture and in vivo. Cyclicity of morphologic features was not found, neither in vivo nor in vitro. The results indicate that: (1) laminin plays a unique role for marmoset Sertoli cell differentiation in vitro compared with other extracellular components; (2) a greater similarity between cells in vivo and in vitro is evident with adult Sertoli cells; and (3) the adult marmoset monkey could provide a primate model for mature Sertoli cells in culture, since there is a close similarity to human adult Sertoli cells in vitro and in vivo. PMID- 1293136 TI - Human sperm acrosin. Further studies with the clinical assay and activity in a group of presumably fertile men. AB - The goals of this study were to determine the effect of the nonionic detergent, Triton X-100, on the recovery of acrosin in the clinical assay (Kennedy et al, 1989), since previous investigations have used higher concentrations for acrosin extraction from spermatozoa; and to establish the minimal acrosin activity in fertile men. The recovered acrosin activity was dependent on the concentration of Triton. A peak in acrosin activity was obtained at 0.01% to 0.02% Triton, the approximate critical micelle concentration (CMC; 0.015%). The bimodal effect of Triton was not due to substrate/buffer alterations, to the degree of acrosomal disruption as assessed by light and transmission electron microscopic examination, or to its effect on the kinetic properties of acrosin, as determined by spectrophotometric analysis of acid-extracted enzyme. However, Triton affected the conversion of proacrosin to acrosin, with peak activation occurring at 0.01% to 0.02% detergent. The acrosin activity of a group of presumably fertile men (as established by the production of offspring under natural conditions) varied from 18 to 42 microIU/10(6) spermatozoa, as assessed by the clinical assay containing 0.01% Triton. Furthermore, men who had initial acrosin values in the low normal range (18 to 25 microIU/10(6) sperm) were observed for 11 months. The acrosin activity of their ejaculates never fell below 17 microIU/10(6) sperm. Thus, it can be tentatively assumed that the minimal levels of acrosin for naturally fertile men are 17 to 18 microIU acrosin/10(6) sperm in this assay. PMID- 1293138 TI - Min Chueh Chang. Experimentalist for whom perseverance, cognitive planning, and the favoring winds of chance paid off. PMID- 1293137 TI - Modulation of immunoradiometric and bioactive follicle stimulating hormone secretion and clearance in young and elderly men during treatment with tamoxifen or flutamide. AB - The secretion and clearance of immunoactive and bioactive follicle-stimulating hormone (FSH) in healthy young men (N = 10) and elderly men (N = 7) during blockade of endogenous sex steroid hormones with tamoxifen, an antiestrogen, and flutamide, an antiandrogen, was investigated. To this end, subjects underwent blood sampling basally every 10 minutes for 24 hours, and then received 2 consecutive intravenous pulses of synthetic gonadotropin releasing hormone (GnRH; 10 micrograms and 100 micrograms) every 2 hours. This paradigm was repeated on two subsequent visits, in which subjects received either flutamide HCl, a specific nonsteroidal competitive antagonist of the androgen receptor (750 mg daily for 3 days), or tamoxifen, a selective antagonist of the estrogen receptor (20 mg daily for 9 days). Serum immunoactive FSH concentrations were measured in each sample by immunoradiometric assay (IRMA). Serum bioactive FSH concentrations were determined by an in vitro bioassay (rat granulosa cell aromatase system) on 24-hour serum pools. Deconvolution analysis was used to analyze both the FSH IRMA 24-hour time series and FSH release after GnRH. Comparisons between young and elderly men of the basal state showed significantly increased 24-hour mean serum immunoactive and bioactive FSH concentrations and significantly decreased free testosterone concentrations in elderly men. By deconvolution analysis, elderly men had a significant decrease in FSH secretory burst duration, and an increase in FSH half-life and FSH secretory burst amplitude compared with younger men. In response to sex steroid receptor blockade in young men, there was a significant increase in mean serum bioactive FSH concentrations during antiandrogen treatment, but not during antiestrogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293139 TI - The detection of alcohol problems in a primary care clinic. AB - The CAGE is a four item questionnaire which is used to help clinicians identify alcohol problems. Charts of 433 primary care patients who were given a medical health form containing the CAGE questions (experimental patients) were compared with charts of 451 patients given a similar form that did not contain the CAGE questions (control patients). Alcohol problems were detected more frequently in the experimental patients (10.6%) than in the control patients (6.7%) (p < 0.05). This difference in detection tended to be most evident for persons with milder alcohol problems (problem drinking) as opposed to more well developed alcohol abuse. Experimental patients (3.7%) also tended to be more likely than control patients (2.9%) to receive active alcohol treatment during their initial medical visit. Medical health screening forms which include the CAGE questions may promote the identification of alcohol problems in primary care. PMID- 1293140 TI - Legislative interventions to increase access to screening mammography. AB - Although numerous studies have established that breast cancer mortality can be significantly reduced through early detection, only a small percentage of women obtain screening mammograms at intervals recommended by the National Cancer Institute, the American Cancer Society, and other major medical organizations. This paper examines the importance of cost as a barrier to routine screening and the state legislative movement to make screening mammography a basic health insurance benefit. Mammography "knowledge, attitudes, and behavior" studies offer conflicting findings on the extent to which cost enters into the decision to have a mammogram. Women seldom report cost as a major reason for postponing or failing to have a mammogram; yet, descriptive studies show a consistently positive relationship between income and mammography use. State mammography reimbursement laws vary greatly with respect to whether screening mammography is a required or optional benefit, payment limits, and eligibility and referral requirements. Although state-specific data on the percentage of women with private health insurance are not available, 1987 National Medical Expenditure Survey estimates for U.S. Census geographic divisions suggest that the New England, East North Central, West North Central, Middle Atlantic, and Mountain states have the highest percentages of women who are privately-insured and, thus, potentially eligible for legislated mammography benefits. Access to screening mammography also is likely to be influenced by the proportion of employer-sponsored health plans that are self-insured and, therefore, exempt from minimum benefit mandates and the extent to which women are aware of the screening coverage. PMID- 1293141 TI - Prevalence of smoke detectors and safe tap-water temperatures among welfare recipients in Memphis, Tennessee. AB - The poor are at high risk for fire- and scalding-related injuries and deaths, many of which could be prevented by installing smoke detectors and reducing residential tap-water temperatures to safe levels. The goal of this study was to measure the prevalence of smoke detectors and safe tap-water temperatures among welfare recipients and compare subjects living in safe and unsafe homes. We interviewed 109 black women residing in inner-city Memphis who were receiving Aid to Families with Dependent Children and inspected their homes for functional smoke detectors and safe tap-water temperatures. Of the 533 residents reported to live in the homes visited for this study, 53.1% were not protected by smoke detectors. More crowded residences were substantially more likely to lack detectors. Most of the smoke detectors which were present were provided by landlords. Of 69 smoke detectors examined, 17.4% did not work. Of the 153 children age 0-5 years living in the homes we visited, 79.1% lived in residences with excessively hot tap water (> 54 degrees C). We conclude that additional efforts are needed to increase the use of smoke detectors and to decrease excessively hot tap water in the homes of welfare recipients. PMID- 1293143 TI - Food commercials during television soap operas: what is the nutrition message? AB - Studies have examined food commercials appearing during daytime, prime time, and Saturday morning programming; none have evaluated commercials aired during soap operas. The purposes of this study were to examine the dietary composition of food products advertised during soap operas and the health and nutrition claims made on their behalf, using current dietary recommendations as a basis of evaluation. A total of 508 commercials videotaped during the top nine daytime serials for five consecutive days, were for food or beverage products. Most foods advertised were rated low in sugar, fat, sodium, and dietary fiber, and health and/or nutrition appeals occurred frequently. However, of the foods advertised as "low cholesterol," 77% were high in fat. Similarly, those foods advertised as low in saturated fat were high in total fat content. Forty-three percent of the food commercials promoting nutrition were for items such as flavored drinks with little nutrient value. Generally, the nutrition messages conveyed in these commercials supported current dietary recommendations, but the way in which the food products were promoted was often inconsistent and confusing, particularly in the area of fat. Nutrition educators need to address these inconsistencies when assisting consumers in interpreting television food advertising messages. PMID- 1293142 TI - Student nurse opinions about the importance of health promotion practices. AB - Senior nursing students (N = 505) attending 13 schools in the NY metropolitan area were administered a questionnaire to assess their beliefs about the importance of health promotion behaviors to the average person. Respondents rated 23 health promotion practices on a Likert scale. The five most important items concerned: knowledge of drug contents and their side effects; the elimination of cigarette and cigar smoking; eating a balanced diet; and using a seat belt. The least important item concerned having an annual exercise test. These results were similar to those found for other health care providers, including physicians, dietitians, and pharmacists. Further, the results were similar to those found in an earlier survey of student nurses. Nurses' attitudes and beliefs seem supportive of health promotion and disease prevention. These attitudes also seem associated with the nurse's role as health promoter. Positive nurse attitudes/beliefs toward health promotion are posited as precursors to the alteration of patient behaviors, although further exploration in this area is needed. PMID- 1293144 TI - Connective tissue growth factor. PMID- 1293145 TI - Structure, function and possible clinical application of transforming growth factor-beta. AB - Transforming growth factor-beta (TGF-beta) is a family of multifunctional 25 kDa proteins. TGF-beta was originally identified because of its ability to induce the growth of normal rodent fibroblasts in soft agar, but is now known as a potent growth inhibitor for many different cell types. In addition, TGF-beta is known to regulate the differentiation of cells, induce chemotaxis of cells, and to induce the accumulation of extracellular matrix proteins. In vivo, TGF-beta stimulates the repair of soft as well as hard tissues. It also acts as a potent immunosuppressant. TGF-beta is produced as latent high molecular weight complexes; since it is produced by many different cell types, and most cells have receptors for TGF-beta, the activation of latent TGF-beta is likely to be an important step in the regulation of its action. TGF-beta exerts its effects by binding to specific cell surface receptors. The type I and type II TGF-beta receptors are suggested to be the most important for signal transduction; a recent report has disclosed that the type II receptor has a serine/threonine kinase domain. Since TGF-beta is a potent growth regulator with multifunctional activity, it may be useful in the treatment of certain clinical disorders. Local application of TGF-beta is shown to accelerate wound healing. Since an increase in TGF-beta activity is often observed in various fibrotic disorders, antagonists for TGF-beta might be valuable in the treatment of such diseases. PMID- 1293146 TI - The growth regulation of keratinocytes. AB - Taken together, all these results suggest that TGF-alpha and amphiregulin are the major growth factors for positive growth control, although we don't know which plays the central role. For negative growth control, TGF-beta is the major factor. However, it remains to be solved which isoform of TGF-beta is naturally involved in keratinocyte growth regulation. PMID- 1293147 TI - Stimulation of keratinocyte migration by growth factors. AB - Migration of keratinocytes from the wound edge is thought to be one of the critical features of reepithelialization. A quantitative migration assay was carried out using normal human keratinocytes. Keratinocytes, seeded on 12 well plates, were grown in serum free, keratinocyte growth medium (KGM, Curabo Co) with 0.08 mM Ca2+. The medium was switched from KGM to keratinocyte basal medium (KBM) 6 h prior to the wounding. Half of the plate's confluent monolayer of keratinocytes was removed with razor blade, and the remaining keratinocytes were incubated in KBM for 16 hrs in the presence of indicated growth factors. After incubation, the cells were fixed and counted at 100 magnification. Migration was quantitated by counting the number of cells in ten successive 125-microns zones. Transforming growth factor alpha (TGF-alpha), acidic and basic fibroblast growth factor (aFGF, bFGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and insulin-like growth factor-I (IGF-I) stimulated the migration of keratinocytes, while TGF-beta suppressed it. PMID- 1293148 TI - Alteration of the chemotactic response of human skin fibroblasts to PDGF by growth factors. PMID- 1293149 TI - The mitogenic effect of transforming growth factor-beta 1 on human fibroblasts involves the induction of platelet-derived growth factor-alpha receptors: implication for wound healing. PMID- 1293150 TI - Differential modulation of bFGF receptors by TGF-beta in adult skin, scleroderma skin, and newborn foreskin fibroblasts. PMID- 1293151 TI - The effects of basic fibroblast growth factor and doxorubicin on cultured human skin fibroblasts: relevance to wound healing. AB - The effects of basic fibroblast growth factor (bFGF) and doxorubicin on cultured human skin fibroblasts were examined in order to determine their relevance to wound healing. bFGF is shown to stimulate fibroblast collagenase production per cell, and this effect in vitro seems to be one explanation for its efficacy in wound healing. Doxorubicin inhibited not only fibroblast proliferation but also collagen production by inactivating prolyl hydroxylase. This result may explain the reduced wound healing in patients undergoing treatment with doxorubicin. These studies indicate the importance of assessing the effects of growth factors on matrix metabolism in order to understand their roles in wound healing. PMID- 1293152 TI - Growth factors and chronic wounds: the need to understand the microenvironment. AB - The care of chronic wounds has become a major health issue in developed countries because of their increasingly elderly populations. There is hope that progress made in understanding and producing growth factors will lead to their successful use to induce faster and better healing of chronic wounds. This report will discuss growth factors in the context of their use in chronic wounds, and will focus on the importance of the wound microenvironment in determining the interactions between growth factors and wounds. We believe that a greater understanding of the chronic wound microenvironment will be of benefit in the optimal use of growth factors. In published studies, we have found that wound fluid taken from acute wounds stimulates fibroblast and endothelial cell proliferation, whereas fluid obtained from chronic non-healing wounds inhibits the growth of fibroblasts, endothelial cells, and keratinocytes. In this report, we describe the effect of these two types of wound fluid on the synthesis of extracellular matrix components. We hypothesize that the chronic wound microenvironment is generally non-conducive to cell growth, and that this may prevent a truly successful use of topical growth factors in chronic wounds. Novel approaches in the delivery of growth factors to wounds may be necessary to overcome these obstacles. PMID- 1293153 TI - A wound healing model using healing-impaired diabetic mice. AB - A quantitative histological approach was employed to evaluate the effects of basic fibroblast growth factor (bFGF) in healing-impaired diabetic mice. The dorsal areas of female mutant diabetic mice, C57BL KsJ db/db (Jackson Lab.), were given two 6 mm-size full thickness wounds with a punch biopsy instrument. After application of bFGF, the wounds were left open. 8 days after wounding, the mice were sacrificed, and histological sections were evaluated using several histological parameters, such as the degree of wound closure, granulation tissue thickness, matrix density, and capillary numbers. Application of 5 micrograms of bFGF for 5 days induced significant responses by all of these dermal parameters when compared to those of non-treated db/db mice (p < 0.001). A minimum of 0.5 micrograms bFGF per day was required for a significant effect. Time-course experiments indicated that the granulation response in bFGF-treated mice peaked between 8 and 12 days and decreased after 12 days, while matrix density continued to increase until the 18th day. PMID- 1293154 TI - The role of growth factor in wound healing. AB - A pig wound healing model was developed to study the morphological processes involved in incisional and excisional wound healing, the immunohistochemical localization of TGF-alpha in wound healing, and the latter's relevance. In incisional wounds, a few layers of epidermis were regenerated after only 32 hours. In contrast, several layers of epidermis were regenerated on day 7 in excisional wounds. In general, the incisional wound model is useful for evaluating tensile strength, while the excisional wound model is suitable for evaluating epidermal regeneration. Immunohistochemical study showed that keratinocytes migrating from wound edges expressed TGF-alpha very faintly, while TGF-alpha was present prominently in the upper several layers of the epidermis adjacent to the wound, which resembled normal epidermis and showed no changes during the wound healing process. PMID- 1293155 TI - Molecular bases for hereditary cancer-prone diseases. AB - Constitutional loss or inactivation of one copy of a tumor-suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8-dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss-of-function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild-type allele of the functionally heterozygous APRT gene resembled that reported for tumor suppressor genes in malignancies in that mitotic non-disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer-prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain-of function mutation at a proto-oncogene and/or the loss-of-function mutation at a tumor-suppressor gene. XP complementation group A (XP-A) LCLs were extremely sensitive to UV-mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV mutagenesis in XP-A. We have succeeded for the first time in rendering XP-A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293156 TI - Xeroderma pigmentosum: recent clinical and photobiological aspects. AB - In Japan, more than 400 patients with xeroderma pigmentosum (XP) have been registered. The major groups are XP-A and variant, while clinically mild types of XP with intermediate levels of unscheduled DNA synthesis (UDS) have recently been increasing. The classical type of XP-A and some of the XP-D patients exhibit neurologic abnormalities. XP individuals display a marked increase in the frequency of skin malignancy. Development of skin malignancies appears to be related to the level of DNA repair capacity; the lower the capacity, the earlier and more frequently the skin tumors develop. Furthermore, the incidence of internal malignancy in XP patients is at least ten times higher than that for the Japanese general population over the age of 40 years. Cultured fibroblasts from XP patients exhibit higher sensitivity not only to UVC but also to UVB. The cellular sensitivity to UVB may correlate to photosensitivity in vivo from a study on a group E patient who showed age-related changes in photosensitivity and cellular sensitivity to UVB. We have also reviewed current status of molecular genetics in XP. PMID- 1293157 TI - Porokeratosis: clinical and cellular characterization of its cancer-prone nature. PMID- 1293158 TI - Alterations of mitogenic responses of mononuclear cells by arsenic in arsenical skin cancers. AB - We have studied the endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan. The effects of arsenic on the mitogenic responses of mononuclear cells (MNC) derived from patients with arsenical skin cancers in that area were evaluated. The subjects enrolled in this study included patients with 1) Bowen's disease, 2) arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 3) non-arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 4) nasopharyngeal cancer and 5) healthy controls from endemic and non-endemic areas. Phytohemagglutinin (PHA) stimulated [3H]thymidine incorporation in MNC in all groups except the arsenical skin cancer group. However, when a low concentration of As2O3 (2.5 x 10(-7) M) was added to PHA stimulated MNC, a tremendous amplification of the uptake of [3H]thymidine was noticed in patients with arsenical skin cancer. In this study, this phenomenon did not occur in cancers not related to arsenic. This result shows that arsenical carcinomas are hyperreactive to its specific etiology--arsenic. Arsenic seems to play a role as a co-stimulant of PHA similar to interleukin-1. PMID- 1293159 TI - Chemoprevention of skin cancer in xeroderma pigmentosum. AB - Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients. PMID- 1293160 TI - Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma. AB - T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293161 TI - Establishment and phenotypic analysis of skin-associated human T cell lines from healthy individuals and patients. PMID- 1293162 TI - Mechanisms of desensitization in delayed cutaneous hypersensitivity--modulation of T-cell response by haptenized amino acid. PMID- 1293163 TI - Structure of desmoplakin and its association with intermediate filaments. AB - Desmoplakins (DPs) I and II are two major related proteins located in the desmosomal plaque where they have been proposed to play a role in attaching intermediate filaments (IF) to the inner cell surface. The predicted amino acid sequence of DP was obtained by analysis of overlapping cDNA clones. Computer aided analysis suggests that DPI will form a dumbbell-shaped homodimer, with a central alpha-helical coiled coil rod domain of 132 nm and two globular end domains. The DPII molecule is missing 599 residues from the central domain, resulting in a rod about one third the length of DPI. The carboxyl terminus comprises three subdomains each containing almost 5 repeats of a 38 residue repeating motif with a periodicity in acidic and basic residues similar to that found in the rod domain of IF proteins. This suggests a possible mechanism by which these proteins might interact. The amino terminus contains groups of heptad repeats that are predicted to form at least two major alpha-helical rich bundles. A series of c-myc-tagged mammalian expression vectors encoding specific predicted domains of DPI were transiently expressed in COS-7 cells. Light and electron microscopical observations revealed that DP polypeptides including the 90 kDa carboxyl terminal globular domain of DPI specifically colocalized with and ultimately resulted in the complete disruption of keratin and vimentin IF. This effect was specific for the carboxyl terminus, as the expression of the 95 kDa rod domain of DPI did not visibly alter IF networks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293164 TI - Epidermolysis bullosa and the search for the basis of hereditary disorders of the skin. AB - During the past two years the application of newer strategies of molecular genetics has resulted in the identification of genes whose mutations underlie five diseases of the skin. This is likely to be but the start of an unprecedented expansion in our understanding of these disorders and, most likely, of our ability to treat them. PMID- 1293165 TI - A model to study the fate of genetically-marked keratinocytes in culture. AB - In this study we demonstrate a method for analyzing the spatial distribution or fate of progeny keratinocytes derived from single progenitor cells. The method relies upon the use of retroviral vectors to introduce a reporter gene into replicating cells and to effect integration and expression of that new gene. All progeny cells from that initial cell inherit and express the transferred gene. The reporter gene is the E. coli beta-galactosidase gene (B-gal), which encodes a histochemically-detectable product in the cytoplasm. Using this method, we show that foci of genetically marked, B-gal positive cells can be readily identified in submerged cultures and we term this grouping of cells a "clonal proliferation unit". Analysis of B-gal stained whole mounts and paraffin sections allows visualization of the proliferative potential and differentiating capacity of clonogenic cells. This model will allow exploration of how agents known to alter epidermal proliferation and differentiation affect lineage relationships. PMID- 1293166 TI - Melanin-related metabolites as markers of melanoma: a review. PMID- 1293167 TI - 5-S-cysteinyldopa in urine and tumors. AB - 1) The urinary 5-S-CD contents in malignant melanoma subjects (n = 135) and non melanoma subjects (n = 204) were measured by HPLC. These results suggest that, as a biochemical marker, periodic measurement of urinary 5-S-CD is quite useful for evaluating the determinations of stage classification (UICC, 1987), and the detection of metastases, the therapeutic efficacy of operation or immunochemotherapy against malignant melanoma. 2) Quantitative analyses of 5-S-CD values in tissues from primary malignant melanoma lesions (n = 24) and pigmentary tumors other than melanomas (n = 136) showed 80.6-821.4 ng/mg and N.D.-55.0 ng/mg respectively. In view of the above findings, it was suggested that the pigmentary tumors can be diagnosed as malignant melanoma if the 5-S-CD value in the tissues is higher than 100 ng/mg. PMID- 1293168 TI - Serum 5-S-cysteinyldopa (5-S-CD) as a marker of melanoma progression. AB - We previously reported that serum 5-S-cysteinyldopa (5-S-CD) tended to elevate earlier and reflect melanoma progression better than urinary 5-S-CD. In patients without metastatic melanomas, serum concentration and urinary excretion of 5-S-CD and 6-hydroxy-5-methoxy-indole-2-carboxylic acid (6H5MI2C) were within the upper limits of normal controls. In this report, we presented more precisely the changes in these melanin-related markers and clinical courses of four melanoma patients. Serum and 24-hour urine samples were serially collected and assayed every 1 to 4 months. Three of them developed stage IV malignant melanomas and died of metastatic disease. 6H5MI2C in serum and urine did not reflect the progression of disease. Among the 4 parameters considered, 5-S-CD in serum appeared to be the best biochemical marker for melanoma progression. Serum 5-S-CD over the upper limit of 10 nmol/L was suggested as a serious sign of the progression of melanoma. PMID- 1293169 TI - Gangliosides of melanoma. AB - The relationships between the ganglioside composition of melanomas and their biologic behavior were investigated. (1) The amount of GM2 and/or GD2 in melanoma cells injected into nude mice correlated with the tumor growth rate. (2) GD2 content of melanoma cell lines correlated with sensitivity to radiation and vincristine. (3) GM2 expression of melanoma cells correlated with sensitivity to lymphokine-activated killer cells. (4) Gangliosides inhibited the proliferation of human T cells stimulated with interleukin-4 or interleukin-2. Based on these results, we proposed a hypothesis for the role of melanoma-associated gangliosides in the biologic behavior of melanomas and suggested a prospective melanoma treatment related to the gangliosides. PMID- 1293170 TI - Melanoma-associated antigen synthesized in vitro for active specific immunotherapy. AB - The immunogenicity of the antigen molecule is a prerequisite for active specific immunotherapy for melanoma. Since most of the melanoma-associated antigens recognized by the murine immune system are known to be not immunogenic in man, a detection and analysis system for melanoma-associated antigens is required to reflect in vivo immune responses in patients with melanoma. One of the promising approaches, an attempt to develop human monoclonal antibodies from B lymphocytes of patients with melanoma, has met with limited success due to the difficulties of producing large amounts of antibodies and using them in immunochemical assays, because most of them belong to the IgM class and have low affinity. Our approach is to utilize the screening of a cDNA expression library constructed from mRNA extracted from cultured melanoma cells with antibodies from patients with melanoma. The cloned cDNA, designated as D-1, had 1029 bp and showed no significant homology with viral and mammalian sequences stored in GENETYX. cDNA D 1 hybridized to a 2.0 kb mRNA species from 3 different cell lines of human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cells, but not from a renal carcinoma cell line, normal peripheral lymphocytes, or normal fibroblasts. The in vivo expression and distribution of mRNA related to cDNA D-1 has been examined in tissue specimens by in situ hybridization and shown to be rather restricted on melanoma cells. The polypeptide antigen encoded by cDNA D-1 may be a valuable immunogen for implementing active specific immunotherapy in patients with melanoma. PMID- 1293171 TI - Analysis of the expression of Hanganutziu-Deicher (HD) antigen in human malignant melanoma. AB - Hanganutziu-Deicher (HD) antigen is classified as a heterophile antigen and chemically defined as a ganglioside and/or glycoprotein containing N glycolylneuraminic acid (NeuGc). HD antigen is absent from normal tissues in humans and chickens but can be expressed in human malignant neoplasms including melanoma. We analysed HD antigen expression in ganglioside and glycoprotein fractions of human melanoma tissues by means of TLC enzyme-immunostaining and Western blotting with biotinylated affinity-purified chicken anti-NeuGc lactosylceramide (anti-HD3) antibody. No HD-antigenic gangliosides were detected in 11 specimens of human melanoma. In the glycoprotein fractions, however, a strong HD-positive band of 58 kD was detected in 3 of 10 specimens and several minor bands (37 kD, 13.5 kD, etc.) were also found in 5 specimens. The positive bands completely disappeared after treatment with neuraminidase. These results suggest that HD antigen is expressed on the carbohydrate chains of glycoproteins but not on those of gangliosides in human melanoma. PMID- 1293172 TI - Integrin expression in malignant melanoma and their role in cell attachment and migration on extracellular matrix proteins. AB - The interaction between melanoma cells and extracellular matrix (ECM) components may be important for invasion and metastasis. The integrins belong to a family of protein heterodimers composed of alpha and beta subunits and the beta 1-integrins are especially important as ECM receptors. We investigated the expression of beta 1-integrins on four human melanoma cell lines (two primary, one from the radial growth phase (RGP) and another from the vertical growth phase (VGP), and two metastatic) and examined their attachment and migration on laminin (LN), type IV collagen (CN) and fibronectin (FN). Among LN and/or CN integrin receptors, only alpha 2 beta 1 (VLA2) was expressed at significantly higher levels in the VGP and metastatic cell lines in comparison to the RGP cell line. In addition, enhanced attachment and migration on LN and CN were significantly inhibited by anti-VLA2 monoclonal antibody (mAb). As to FN receptors, alpha 4 beta 1 and alpha 5 beta 1 expression was heterogeneous among the cell lines, however, it was directly related to enhanced attachment and migration on FN, which also could be inhibited by anti-VLA4 and anti-VLA5 mAbs. Our findings provide evidence for a role in beta 1-integrins, in particular alpha 2 beta 1, in melanoma progression and metastasis. PMID- 1293173 TI - Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins. AB - We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis. PMID- 1293174 TI - Oncogenes in melanomas. PMID- 1293175 TI - Aspects in neurofibromatosis from the viewpoint of dermatology. AB - The neurofibromatoses are a heterogenous set of conditions having clinical manifestations such as skin, nervous system, bone and eye disorders. The clinical pictures of the patients will obviously differ, and there is considerable variation of manifestations even within a family. During the last twenty-five years, one thousand and two hundred patients with neurofibromatosis were personally examined. Almost all our patients had classical von Recklinghausen disease. But in addition to these cases, there are 28 cases of NF-2 and 10 patients which we call multiple neurilemmomatosis. Also, there are related groups of patients with conditions which were not neurofibromatosis, such as 40 cases of localized multiple neurofibromas and 61 cases of localized cafe-au-lait spots. The features of neurofibromatosis in Japan are not different, compared with foreign countries, except increased pigmentation is more common. In addition to cafe-au-lait spots, some 20% of Japanese neurofibromatosis patients have pigmentary conditions which I termed hairy fuscoceruleus spots. These spots are blue-brown in colour, and one can see coarse hairs in them. Our recent study indicates that the patients with neurilemmomatosis have loss of heterozygosity of chromosome 22, the same position as the site of patients with NF-2. Neurilemmomatosis may be classified as an NF-2 without acoustic tumors. PMID- 1293176 TI - Nosological considerations of the neurofibromatoses. AB - We are on the threshold of evaluating the NF1 and NF2 loci with respect to variant forms of the neurofibromatoses. Genetic mapping of NF1, gene cloning and characterization of its encoded product, neurofibromin, provides a framework for the evaluation of the variant forms of NF. This may also apply to NF2 variant forms in the near future. The mapping approach in evaluating variant forms of NF should begin with the rigorous clinical assessment of familial cases whereby the establishment of genetic linkage in families with overlap syndromes might determine if either NF1, NF2, or a separate locus is involved in the phenotype. Conditions mapping to the NF1 locus could then be screened for mutations in hopes of identifying the etiologies of the variant forms of NF. Mutation identification should provide a molecular-based classification scheme for the variant forms of NF, now tentatively divided into alternative and related forms. It is expected that the nosology of the neurofibromatoses will most certainly change as more is learned of the NF1 and NF2 loci. PMID- 1293177 TI - The neurofibromatosis type 1 (NF1) gene: identification and partial characterization of a putative tumor suppressor gene. AB - The NF1 gene has been isolated and partially characterized. The discovery that NF1 functions as a ras GTPase activator protein has led to new opportunities for understanding the pathology of this disease. The approximately 11 kilobase (kb) NF1 consensus cDNA sequence contains an open reading frame encoding a peptide of 2818 amino acids. DNA blot and polymerase chain reaction analysis indicate that the NF1 gene consists of over 50 exons spanning 300 kb of chromosome 17. PMID- 1293178 TI - The prenatal diagnosis of NF-1 and NF-2. PMID- 1293179 TI - The tuberous sclerosis complex, a prototype of hamartiosis and hamartomatosis. PMID- 1293180 TI - The neuropathology of tuberous sclerosis. AB - Tuberous sclerosis, an autosomal dominant disorder associated with hamartomas in multiple organs, prominently affects the central nervous system; principle lesions include subependymal nodules and giant cell astrocytomas, white matter heterotopias, and cortical tubers. Histologic, immunocytochemical, and ultrastructural features of these processes suggest they have their basis in abnormal cell migration and differentiation. Aberrant expression of cystoskeletal proteins appears to be common to the multisystem hamartomas of this disorder and may, in part, underlie their pathogenesis. PMID- 1293181 TI - CT and MR imaging of intracranial tuberous sclerosis. AB - CT and MR have permitted radiology to play a greater, but not definitive, role in detecting the pathologic components of tuberous sclerosis. SEN may be identified in only 80% of patients. Tubers are more ubiquitous and readily identified by MR in children and adults when the brain is myelinated. Since tubers are predominantly peripheral hypomyelinated lesions, the detection of small lesions may be delayed until an infant is over 16-18 months of age when the myelin will have extended to the junction between the cortical white and gray matter. SEGA typically evolve later during the first and second decades of life. Successful genetic counseling implies a need to detect tuberous sclerosis at a stage during infancy when imaging may fail to confirm the diagnosis, so tuberous sclerosis remains a clinical diagnosis. PMID- 1293182 TI - Biochemical study of cells cultured from a patient with tuberous sclerosis. PMID- 1293183 TI - Tuberous sclerosis complex: genetic aspects. AB - Much has been learned about tuberous sclerosis complex (TSC) since it was described at the end of the nineteenth century. TSC was recognized to be a genetic disease with autosomal dominant inheritance in the early twentieth century. The prevalence in the general population is at least 1 in 10,000 with two-thirds of cases occurring sporadically and one-third of cases being familial. The disease exhibits variable expression which may cause mildly affected individuals to be undiagnosed. Because the aberrant or missing proteins which result in TSC have eluded investigators, a positional cloning approach has been pursued to find the mutated genes. Genetic linkages have been reported to chromosomes 9, 11, and 12. There is definite evidence for a TSC-causing locus on chromosome 9 which is thought to account for between one-third and one-half of all familial cases. Investigators have narrowed the location on chromosome 9 to approximately two megabases of physical distance. There is some evidence for a locus on chromosome 11 which probably accounts only for a small percentage of familial cases. The locus proposed on chromosome 12 was reported by a single group and has not been confirmed by other research groups. Evidence for genetic heterogeneity is abundant. There is definitely a TSC-causing locus on chromosome 9q (TSC-1) and there is at least one additional locus, maybe more than one. As the molecular basis of TSC unfolds, new insight will be gained about the protean nature of the disorder and the genetic heterogeneity. PMID- 1293184 TI - Mechanisms of local, low-dose UVB-induced immunosuppression in contact hypersensitivity. AB - Preirradiation of contact sensitizing sites to low-dose ultraviolet B (UVB) renders animals unresponsive to challenge reaction. This unresponsiveness is known as local, low-dose UVB-induced immunosuppression. Although researchers in this area have developed theories, the exact mechanisms of UVB-induced immunosuppression are still a matter of controversy. This article reviewed various scientific data on UVB-induced immunosuppression, categorizing them into individual sequential steps in the whole cascade. PMID- 1293185 TI - Donovanosis. PMID- 1293186 TI - Expression of neuron-specific enolase immunoreactivity by cutaneous and extracutaneous Langerhans-cell histiocytoses ("X"). AB - The immunohistochemical expression of Neuron-Specific Enolase (NSE) and of S100 protein was studied in 10 cases of cutaneous and 19 cases of extracutaneous Langerhans cell histiocytoses (LCH), including acute/proliferative forms (cutaneous Letterer-Siwe disease) and chronic/granulomatous forms (eosinophilic granuloma, Hand-Schuller-Christian disease). Of the LCH cases, 18 (62%) exhibited detectable NSE-immunoreactivity as compared to 82.8% for S100. NSE expression was found more frequently and intensely within acute (as compared to chronic) forms of LCH. This result lends further support to the cellular unicity of LCH, but also suggests some degree of heterogeneity among LCH cells. It can be speculated that NSE-expression is correlated with the proliferation/activation state of (abnormal) Langerhans cells. PMID- 1293187 TI - Significance of antibodies to phenolic glycolipid-I in leprosy diagnosis. AB - A gelatin particle agglutination assay for the detection of anti PGL-I antibodies in 40 clinically diagnosed and variously classified groups of leprosy cases revealed elevated PGL-I antibody titers in 85% of cases. In contrast, the slit skin smear examination was positive in only 30% of cases. It was further observed that, out of 28 cases with Bacteriological Index (B.I.) zero, 22 cases (78.5%) had significant levels of PGL-I antibodies. There was no case in which the slit skin smear was positive and the PGL-I antibody titer was not significant. The elevated titers of PGL-I antibody better correlated (84%) with histopathological findings than did B.I. Thus it was concluded that estimation of PGL-I antibody titer is a better supplement to clinical diagnosis than B.I. Significant levels of PGL-I antibody were seen in 85% of cases who had no earlier chemotherapy or were treated for less than 2 months. Similar findings were observed in 12 patients who were on MDT for more than 5 months but for less than 2 years. In order to determine the significance of anti PGL-I antibodies in monitoring the response of patients to chemotherapy, a longer follow up with a greater number of cases should be contemplated. PMID- 1293188 TI - Influence of oral metronidazole on the endocrine milieu and sebum excretion rate. AB - As part of a study of the mechanism of metronidazole's efficacy in the treatment of acne and rosacea, its effects on the endocrine milieu and sebum excretion rate were assessed. Thirteen healthy males received oral metronidazole treatment (500 mg/day) for 4 weeks. Serum sex hormone levels were determined in all 13 subjects and the sebum excretion rate was determined in seven of them, before and after treatment. We measured serum levels of estrone (E1), estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG). There were no significant changes in E1, T, FT, DHT, or SHBG levels, but E2 and DHEA-S levels decreased significantly after treatment. In all seven subjects in whom the sebum excretion rates were determined, the amount of facial skin surface lipids decreased significantly after treatment. These results suggest that metronidazole exerts its clinical effects through suppressing the sebum excretion by a mechanism other than anti-androgenic action. PMID- 1293189 TI - The role of metal allergy and local hyperhidrosis in the pathogenesis of pompholyx. AB - Pompholyx (Dyshidrosis) is a disease of unknown etiology presenting as symmetrical, vesicular hand and foot dermatitis. To clarify the pathogenetic role of sweat and metal allergy, twenty five patients with pompholyx were examined with respect to their perspiration volume using equipment that continuously recorded the local perspiration volume. Patients were also examined for metal allergy by patch testing and oral challenge tests. The perspiration volumes were measured using recently developed equipment for continuous recording of local perspiration volume (Kenz-Perspiro oss-100). The perspiration volume of pompholyx patients was found to be 2.5 times higher than that of age-matched normal controls. Twenty percent of the patients showed sensitivity to chromate, 16% to cobalt, and 28% to nickel on patch testing. Six patients with positive results were challenged orally in a controlled trial with 2.5 mg nickel, 1 mg cobalt, or 2.5 mg chromium. Four of them (67%) showed vesicular reactions on their hands with challenge testing. These results indicated a sensitivity to metal compounds which, in combination with local hyperhidrosis, may contribute to the development of vesicular lesions in pompholyx. PMID- 1293190 TI - Nodular scleroderma in systemic sclerosis under D-penicillamine therapy. AB - A case of systemic sclerosis (SS) which developed keloidal lesions (nodular scleroderma) on the chest during D-penicillamine (DPC) therapy is reported. The 36-year-old woman showed rapidly progressing skin sclerosis with lung and esophageal involvement, and DPC was started at the age of 38. Skin sclerosis as a whole had improved to some extent, when keloidal nodules developed on the upper chest at the age of 44. Since there were no other findings suggestive of adverse reactions caused by DPC, we speculate that activation of the fibroblasts in these lesions occurred despite the suppressive effect of DPC. PMID- 1293191 TI - An AIDS patient with atopic dermatitis-like eruption responsive to systemic anti fungal treatment. AB - Patients with the acquired immunodeficiency syndrome (AIDS) often develop unusual skin complications. We describe a case of a 58-year-old man with AIDS who had a history of multiple transfusions with anti-hemophilic factor A. He developed papulovesicular and lichenified skin lesions on his head, face, neck and the extensor aspects of his extremities accompanied by severe pruritus. Atopic dermatitis was suspected; however, intensive treatment with a potent topical corticosteroid and a systemic antihistamine failed. In addition to the decreased subset of CD4-positive lymphocytes characteristic of AIDS, this patient showed an elevated level of serum IgE particularly specific for Candida albicans, probably because he had a chronic candidial infection of the digestive tract. Oral administration of anti-fungal agents Diflucan and Fungizone produced almost complete relief from the atopic dermatitis-like skin disease within 2 weeks. PMID- 1293192 TI - The effects of crowding on adults of Philophthalmus nocturnus grown in domestic chicks. AB - The effects of crowding on growth, reproduction, rate of recovery and site of infection of Philophthalmus nocturnus were investigated by infecting various groups of day-old chicks with 25, 50, 75, or 100 excysted metacercariae and examining them at 10 or 25 days post-infection. Considerable reduction in the body length and the size of the gonads was noticed in flukes grown under crowded conditions. Crowding also caused some change in the habitat of flukes, but had no effect on their rate of recovery. Very few flukes reached the ovigerous stage under overcrowded conditions and none reached the embryonated larval stage. PMID- 1293193 TI - Ultrastructure of the spermatid and spermatozoon of Macracanthorhynchus hirudinaceus. AB - The ultrastructure of the spermatid and spermatozoon of Macracanthorhynchus hirudinaceus (Archiacanthocephala) was studied by means of transmission electron microscopy. The flagellum and nucleus in the spermatid gradually expanded simultaneously. The karyoplasma of the spermatid transformed into dense inclusions and a multibarrel structure, which were also found in the spermatozoan body. The multibarrel structure was located close to the flagellum and consisted of many irregular microtubes. The flagellum of the developing spermatozoon was observed in a concavity of the spermatid nucleus. The microtubule arrangement of the flagellum was "9 + 2". No mitochondria or acrosome were observed in spermatozoa. PMID- 1293194 TI - The effect of catecholamines and catecholamine antagonists on the third larval moult of Dirofilaria immitis in vitro. AB - Various catecholamines and catecholamine antagonists have been examined for their effects on the third larval moult of the parasitic nematode. Dirofilaria immitis, cultured in vitro. The non-selective alpha and beta agonist, noradrenaline, and the beta agonist, isoprenaline, had no effect on the timing of the third stage moult when used at a concentration of 10(-5) M. The alpha-adrenergic antagonist, phentolamine, resulted in worm mortality at 10(-5) M. At 10(-7) M, both phentolamine and the beta-antagonist, propranolol caused a significant reduction in the numbers of larvae capable of completing the third stage moult. Idazoxan, an alpha 2-antagonist, at 10(-5) M did not affect worm mortality but did completely prevent ecdysis. The potential of these compounds as possible filaricides is discussed. PMID- 1293196 TI - Efficacy of ivermectin against Parastrongylus malaysiensis infection in rats. AB - The efficacy of ivermectin on experimental infections of P. malaysiensis in rats was determined. Ivermectin was 99.4% and 97.9% effective at a dosage of 400 meg and 800 meg respectively at seven days post-infection. The same two dosages of ivermectin when given at 14 days post infection had an efficacy of 100%. However, as an adulticide it had only 40.7% efficacy. Ivermectin may therefore be useful for the treatment of parastrongyliasis due to the larval stages of the worm which can cause significant pathology in man and animals. PMID- 1293195 TI - The use of 35S-labelled Toxocara canis to determine larval numbers in tissues. AB - The potential of using 35S-labelled larvae to determine the number of second stage Toxocara canis larvae present in the tissues of infected animals was assessed. Infective larvae were labelled by in vitro culture with medium containing 35S-methionine. The amount of radiolabel attached to larvae decayed exponentially with time and had an in vitro mean half life of 3.54 +/- 0.65 days. The 'lost' radiolabel was incorporated into proteins which formed part of the worm's excretory/secretory products. The levels of radioactivity present in different organs of BALB/c mice, infected with 35S-labelled T. canis larvae, varied over the course of infection. Initially most of the radioactivity was present in liver, but over the course of infection 35S liver levels gradually decreased and brain levels increased. By day 14 post-infection the majority of the isotope was present in the brain (p < 0.01). Assessment of antibody levels on day 14 post-infection showed that infection with 35S labelled T. canis larvae induced the production of parasite-specific IgM, IgG and IgG1 antibodies. PMID- 1293197 TI - Immunodiagnosis of human trichinellosis using excretory-secretory (ES) antigen. AB - Infective first stage larvae of Trichinella spiralis were recovered from muscles of laboratory infected mice by digesting the muscles with 1% HC1-1% pepsin and collecting the larvae by modified Baerman's method. The larvae were cultivated in a serum-free medium for 18 h. The ES antigen obtained from the culture medium was used in an enzyme-linked immunosorbent assay (ELISA) for detecting IgG antibodies to T. spiralis in serum samples collected from three groups of individuals. The individuals of the first group were parasitologically confirmed trichinellosis patients, while those of group 2 were patients with other helminthiasis and group 3 were healthy, parasite-free individuals. The specificity of the assay was 100%. The sensitivity of the test was also 100% when performed on sera of group 1 collected at days 57 and 120 after infection. Sera collected earlier (day 23) and those collected 700 days after infection had negligible reactivity. Thus IgG ELISA using ES antigen of the L1 was useful not only for diagnosis but also in evaluation of cure. Western blot analysis revealed that specific antigens of T. spiralis were 94, 67, 63, and 39 kilodalton components. PMID- 1293198 TI - Radiolabelling of the excretory-secretory and somatic antigens of Anisakis simplex larvae. AB - Anisakis simplex larvae were cultured in vitro in medium containing 35S methionine for ten days. The medium and the larval tissues were analysed for biosynthetically labelled polypeptide by sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography. Immunoprecipitates with positive and negative human antisera were similarly analysed, using Staphylococcus aureus to absorb immuno-complexes. ES products of Anisakis larvae contained many polypeptides with molecular weights of less than 200 K. 180 KDa and 40 KDa polypeptides in ES products reacted with IgG in Anisakis-infected human sera. Somatic extracts also contained many polypeptides with molecular weights of less than 200 K. One of these polypeptides with a molecular weight of 130 K reacted with IgG in Anisakis-infected human sera. These polypeptides did not react with other nematode-infected human sera. PMID- 1293199 TI - Isoenzymatic pattern and structure of glutamate dehydrogenase from Ascaris suum. AB - The isoenzymatic pattern of glutamate dehydrogenase (GDH) has been described for Ascaris suum a parasite of Sus scrofa domestica. Only one band of activity has been revealed, suggesting a monomorphic condition for this enzyme. Also, the structure of GDH has been assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. Only one subunit was present with a molecular weight of about 55,000. A hexameric structure for GDH of A. suum is suggested. PMID- 1293200 TI - Traditional Crow Indian health beliefs and practices. Toward a grounded theory. AB - An important element in American Indian cultures is a holistic view of wellness. Nurses attempting to provide holistic, culturally sensitive health services to American Indian clients must assess the cultural orientation of their clients and have culture-specific knowledge. A pilot qualitative study was conducted at the Crow Indian Reservation in south central Montana. Qualitative analysis of data identified categories of traditional contemporary health practices of Crow Indians. These categories are use of rituals/ceremonies, indigenous healers, and sacred objects. Five patterns of use of traditional health practices were also discovered. These are (a) initial use of traditional practices followed by modern health services, (b) initial use of modern health services followed by traditional practices, (c) simultaneous bicultural use, (d) traditional use only, and (e) modern use only. PMID- 1293201 TI - Improving organ donation rates in the black community. AB - The risk of developing end-stage renal disease is four times higher in the Black than in the White population. The number of Blacks on dialysis or on the waiting list for transplantation continues to grow due to an insufficient number of suitable organ donors. Same-race transplants have been shown to be more successful when blood types and human leucocyte antigens are used as the matching criteria. The low levels of organ donation by Blacks has been attributed to a number of factors. This article reviews some of the more complex factors (e.g., social practices, religious beliefs, and cultural expectations) affecting the organ donation decision. In addition, some implications and strategies are suggested that may increase the rate of organ donation in the Black community. PMID- 1293202 TI - Cultural considerations. PMID- 1293203 TI - The Soviet health care system: Glasnost, Perestroika, and health problems of the 1990s. AB - Worsening economic conditions and political turmoil in the Soviet Union have led to significant health care problems in the 90s. The Soviet people are calling for reforms of education and the health care system that extend beyond the unsuccessful program of glasnost and perestroika. The purposes of this article are to (a) describe the health care system in the Soviet Union, (b) highlight health issues and concerns of the Soviet people, (c) describe the education of physicians and nurses, and (d) compare and contrast common and unique factors about Soviet health care with health care in the West. The data base for the article was collected from observational site visits, on-site focused interviews with key informants in Kiev and Moscow, and extensive computerized and manual literature searches. Data were also gathered from questionnaires distributed to a convenience sample of 17 nurses in Moscow. Study results include demographic information and the state of nursing education and research, including availability and access to resources to conduct nursing research in Moscow. PMID- 1293204 TI - Perspectives on nursing care of Chinese Americans. AB - Chinese population growth in the United States is expected to accelerate more rapidly than that of any other Asian group in the coming decades. As a result, nurses will be encountering members of this diverse and rich cultural group more frequently. A better understanding of the cultural beliefs, customs, and health care practices of Chinese Americans can only improve the quality of nursing care provided for these clients. Awareness of the barriers to health care that confront many Chinese Americans will be useful in designing appropriate nursing interventions. Knowledge of the positive and negative effects of some traditional Chinese health care practices can be incorporated into individualized client teaching plans. PMID- 1293205 TI - A holistic approach to vaso-occlusive pain crisis in children with sickle cell disease. AB - A significant number of children with sickle cell disease suffer from episodes of acute recurrent vaso-occlusive pain crisis. Unfortunately, very limited published information is available about specific pain management practices used for these patients. There is even less information available on the use of an interdisciplinary approach for management of sickle cell crisis pain. The purpose of this article is to review the genetic cellular pathophysiology, the sickling process, vaso-occlusive crisis, and management of pain associated with sickle cell disease in children. The article further examines an interdisciplinary approach for the management of vaso-occlusive pain crisis. PMID- 1293206 TI - The "big three" cardiovascular risk factors among American blacks and Hispanics. AB - Today's chronic diseases require "treatment" by shifting control of the outcome from the provider back to the individual and the environment in which one functions. There is a strong need to consider the individual in the context of ethnicity and culture, which express themselves in the prevalence and magnitude of risk factors, the biological impact of risk factors and expression of disease, and the potential for control of unhealthy behaviors. Educational and screening programs related to the risk factors of cigarette smoking, hypertension, and cholesterol must be structured so that recommended life-style changes are compatible with the individual's cultural values and beliefs. PMID- 1293207 TI - Issues related to dust aerosols in the magnesite industry. I. Chamber exposure. AB - The present paper is an overview of the experimental research into the effects of flue magnesite dust in the magnesite industry in which the raw material (magnesite) is processed into refractory magnesite clinker. The issues related to dust are divided into two problem areas: a) dust aerosol arising in the process of ore mining and consisting largely of magnesite (MgCO3) and b) dust aerosol originating during ore baking in rotatory furnaces and made up mostly of MgO. Thus, larger groups of people become exposed to these aerosols as a result of solid particles escaping into the atmosphere than in the case of occupational exposure. Experimental research carried out on laboratory animals after chamber exposure provided findings on the deposition, retention and elimination of magnesite dust, on impaired balance between magnesium and calcium leading to damage of biological membranes, on how the immune profile or reproduction and embryogenesis is impacted as well as on the possible interaction with sodium salicylate as a result of an impaired acid base balance. These findings are followed up by evidence produced in the course of biological monitoring (Part II). PMID- 1293208 TI - The past and future of tropical medicine in Czechoslovakia. AB - The authors present a short historical review on the developments in the Czechoslovak tropical health studies with special reference to the post WW II period. Perspectives for future expansion are likewise outlined. PMID- 1293209 TI - Pilot studies on the occurrence of some infectious diseases in two different areas in south Yemen (Aden). Part I. Parasitology. AB - Two pilot studies on malaria, leishmaniasis, schistosomiasis and intestinal parasites were carried out in 104 children 6-15 years old from villages in the lowland and highland areas of South Yemen in November 1988. Some of the results presented are in the order lowland and highland. The occurrence of malaria parasites in blood smears was 6.7% and 3.8%. P. falciparum was detected only. The antimalarial IFAT antibodies were proved in 66.7% and 11.5% respectively. IFAT antibodies against leishmania were in 43.8% and 39.3% respectively of sera examined. Ova of S. haematobium diagnosed with the frequency 29.0% and 13.3% respectively. S. mansoni infection was found in 19.2% of examined children in highland only. From parasites found in stool specimens should be mentioned E. histolytica (42.3% and 36.8%), G. lamblia (34.6% and 35.1%). The other intestinal protozoa were less frequent. Further details of sex and age groups distribution are mentioned. PMID- 1293210 TI - Vertical transmission of hepatitis B in north India. AB - A total of 2337 mother-baby paired sera were screened for the presence of hepatitis B surface antigen. Fifty eight mothers (2.48 per cent) were positive for HBsAg. Six babies (10.3 per cent) were positive for HBsAg at birth. The risk of the babies acquiring the infection during the first year of life varied with the serological status of the mothers. In HBeAg positive mothers the babies were at the greatest risk, with 11/15 (73.3 per cent) babies acquiring the infection by twelve months. If the mothers were only HBsAg positive the risk was lower (17.3 per cent), and if the mother was anti-HBe positive also then the baby had the least chance of becoming infected (9 per cent). PMID- 1293211 TI - Qualification of long-stored samples of serum banks for seroepidemiological studies. AB - Serum samples were tested for antibodies against polio virus and measles virus from two serum banks after having been stored under different conditions for several years. The results are compared with those ones obtained immediately after sampling. Despite of small increases of antibody-negative samples and of small decreases of the titres the suitability of the samples stored could be shown. Special attention should be given to the establishment, e.g. in the framework of Expanded Programme on Immunization of the World Health Organization and in order to study new pathogens unknown to date, and the technical preconditions for that should be planed. PMID- 1293212 TI - Diagnosis of mycobacterial infection in acquired immunodeficiency syndrome (AIDS) patients and HIV carriers. AB - Differences in tuberculosis diagnosis between infected and non-infected HIV patients were described. In Barcelona, tuberculosis is present in 41.6% of 851 patients in whom AIDS was detected between 1981 and the first quarter of 1990. We reviewed the results of the methods used for tuberculosis diagnosis in 270 AIDS patients controlled in our hospital, in whom tuberculosis was detected (33.3%), and we compared these data with the results obtained in HIV carriers with tuberculosis and with tuberculous patients without HIV infection. Statistically significant differences were found between the three groups with respect to sex, age, results of Ziehl-Neelsen stain in pulmonary specimens and skin test reaction; between AIDS patients and the non-HIV infected population differences were observed in tuberculosis site. Positive skin test reaction diminished from tuberculous individuals non-HIV infected (95%), to HIV carriers with tuberculosis (71.8%) and AIDS patients with tuberculosis (21.8%). Acid-fast smears from pulmonary specimens were positive in 35.7%, 23.5% and 43.7% respectively. Statistically significant differences were found in tuberculosis localization between tuberculous patients non-HIV infected and tuberculous patients with AIDS, in the last group tuberculosis lymphadenitis was the most frequent localization (33.3%) of extrapulmonary tuberculosis, followed by abdominal tuberculosis (15.5%). The incidence of HIV infection among tuberculous patients was 4.6 in our study, but could be higher if patients between 19 and 30 years old were always checked for anti-HIV antibodies. PMID- 1293213 TI - Antibacterial properties of the Vietnamese cajeput oil and ocimum oil in combination with antibacterial agents. AB - Main antibacterially active agents obtained from plants-Cajeput essential oil- 1,8 cineol, linalool, alpha-terpineol and terpinen-4-ol, for example from Melalleuce leucadendron (Myrtaceae) as well as essential oil from Ocimum gratissimum (Labiatae) were combined in tests in vitro with selected antibiotics. Above mentioned plant products were found to be effective medicaments for local application in modern medical practice. Combinations with antibiotics potentiated their therapeutical action. On the basis of tests in vitro the synergistic action of these two kinds of medicaments, i.e., preparations traditionally used for a few last decades--antibiotics--might be well applied for therapeutical needs. PMID- 1293214 TI - Yeasts at different mucosal sites in patients with carcinoma cervix before and following radiotherapy. AB - The yeasts isolated from four superficial sites and blood were studied before and during radiotherapy in patients with carcinoma of the cervix. Significant yeast growth increased markedly in all four superficial sites during the 1st and 2nd week following radiotherapy. By the 4th week the count had decreased in all samples except in stool of 4 patients. Candida albicans was the most frequent isolate (54.3%) followed by C. tropicalis (28.3%). PMID- 1293215 TI - C-reactive proteins, immunoglobulin profile and mycobacterial antigens in cerebrospinal fluid of patients with pyogenic and tuberculous meningitis. AB - Cerebrospinal fluid (CSF) samples were collected from 12 patients with pyogenic meningitis (PM), 19 with tuberculous meningitis (TBM), 20 with clinically suspected but not definitely proved cases of tuberculous meningitis (STBM) and 12 normal controls. C-reactive proteins, immunoglobulins G, A, M and mycobacterial antigens were estimated in the CSF samples. Seven out of 51 (13.7%) samples obtained from the patient groups were positive for CRP. Immunoglobulins M and A were significantly raised in the PM group. When the TBM and STBM groups were compared with the controls a highly significant increase was obtained for all immunoglobulins. Mycobacterial antigens/epitopes were identified in 36.8% samples with TBAGB1 and TB68-H monoclonals and in 26.3% with WTB72-A2. In case of patients with suspected TBM, 6.6% were positive with TBAGB1 and WTB72-A2 and 13.3% with TB68-H. However, non-tuberculous patients also reacted with WTB72-A2 (10.5%) and TB68-H (21.0%). This is, to the authors' knowledge, the first report on the presence of CRP in the CSF. Technique for immunoglobulins in CSF is also updated in this paper. We infer that the monoclonal antibody TBAGB1 and immunoglobulins G and A may be safely considered as diagnostic markers of TBM. Estimation of CRP in CSF samples may be made to give a preliminary or additional diagnosis of meningitis regardless of its aetiology. PMID- 1293216 TI - In vitro stimulation of human lymphocytes by alpha, beta and delta toxins and toxoids of Staphylococcus aureus. AB - Alpha, beta and delta toxins of Staphylococcus aureus stimulate human peripheral blood lymphocytes to blastic transformation and formation of IgM, IgG and IgA. The toxins are efficient at concentrations that are not toxic for the cells in culture. A dose of a toxin suitable for stimulation is 100 ng/ml but a stimulation can be observed also at 10 ng/ml, in the case of Ig formation even at a concentration of 1 ng/ml. Toxoids are approximately as effective to elicit blastic transformation as the toxins themselves, their efficiency to stimulate Ig formation being somewhat lower but significant. Alpha and delta toxins and toxoids at the appropriate concentration appear to act as medium-strength polyclonal activators of lymphocytes. Beta toxin and its toxoid are weak polyclonal activators. PMID- 1293217 TI - [Clinical study on symptoms in patients with strongyloidiasis]. AB - We treated strongyloidiasis patients and obtained the following results: Of the 299 patients (184 males and 115 females), 81 patients (27.1%) had no complaints before treatment, 218 patients complaints of some symptoms, including arthralgia and/or lumbago (28.4%), abdominal pain and/or borborygmus (19.3%), numbness of extremities (18.1%), constipation (16.3%) and itching (15.7). We treated 219 patients with mebendazole and symptoms improved after treatment described below: Thirty-seven of the 63 patients (58.7%) with arthralgia and/or lumbago improved. Twenty-seven of the 36 patients (75.0%) with numbness of extremities improved. Thirty-one of the 32 patients (96.9%) with heartburn improved. We treated 26 patients with mebendazole plus thiabendazole and twelve of 14 patients (85.7%) with abdominal pain and/or borborygmus were improved after treatment. We treated 54 patients with ivermectin and five of 18 patients (27.8%) with arthralgia and/or lumbago were improved after treatment. PMID- 1293218 TI - [Detection of verotoxin-producing Escherichia coli using polymerase chain reaction from dairy cattle]. AB - The vero cytotoxin (VT) is responsible for hemorrhagic colitis and hemolytic uremic syndrome. Polymerase chain reaction (PCR) was used to detect VT-producing coliform bacteria from dairy cattle. It was found that 39 (33.3%) of the 117 fecal samples examined were recognized with VT genes in BGLB enrichment broth by the PCR method (named BGLB-PCR). Of the VT-positive samples, 31 samples (26.5%) were found to have VT-producing Escherichia coli. Frequencies of isolation in younger cattle (under 5 months) were 31.3-32.9%. On the other hand, the PCR method using the bacterial suspension of some colonies from DHL selective isolation medium (named DHL-PCR), was used for 105 samples. The DHL-PCR was validated according to the number of colonies tested for detecting VTEC. When using E. coli strains which have been stored after isolation by the conventional culture method, the VT-producing strains found were 7 (10.3%) of the 68 isolates tested. The 101 out of the 108 VTEC strains from cattle were classified into 14 O groups. 4 O serogroups (O26, O111, O145, O157) from 60% of VTEC positive cattle, were also the most common in humans with diarrhea. All E. coli O157:H7 isolates failed to ferment after 48 hrs and to hydrolyze 4-methyl-umbelliferyl-beta-D glucuronide (MUG). These results suggests that cattle may play an important role in human VTEC infections. The BGL B-PCR technique is usefull in ecological studies for VT-producing pathogens. PMID- 1293219 TI - [The 5th report on long-term chemotherapy using erythromycin (EM) for chronic lower airway infection--cases followed over 7 years]. AB - Clinical studies were made over 7 years on 9 cases to whom long-term chemotherapy with EM was administered for chronic airway infection. 1) Clinical effectiveness: Highly effective in 8 cases; Improvement in QOL was observed in 8 cases. Bacteriological effect: In 7 cases, pathogenic bacteria disappeared. 2) No side effects were observed. 3) Changes in PaO2 levels with the passage of time: In most cases, PaO2 reached a plateau within 1 year. Although in some cases, there was subsequent elevation. 4) The frequency of catching cold over the 7 years period was low with an average of 1.2 times/year per subject. In only 2 cases were subject hospitalized due to acute exacerbation triggered by a cold. 5) Mucociliary transport improved in 7 out of 8 cases examined. However, only 4 of these recovered normal transport. The effect of EM in the other cases in which clinical improvement was not demonstrated was deemed slightly effective. On the basis of the above findings, it was suggested that long-term chemotherapy using EM was clinically efficacious. This is based on the fact that its efficacy, including amelioration of QOL appeared within one year of the initiation of therapy, and continued without decline for over 7 years. PMID- 1293220 TI - [Isolation of MRSA from inpatients, staff and environment in the hospital]. AB - The state of MRSA contamination of inpatients, hospital staff, and the hospital environment was evaluated. Nasal, pharyngeal, and digital samples from 182 patients admitted in September and October, 1990, and 288 hospital staff members and sputum, urine, and feces of the inpatients were cultured. Environmental contamination was examined in samples collected from the air by air sampling and from the floor by the wiping method. The MIC and the coagulase type of the MRSA obtained were determined, and their relationships were evaluated. MRSA was detected in 9.5% of nasal samples, 7% of pharyngeal samples, 10% of sputum samples, 0% of urine samples, and 2.6% of fecal samples from the 182 inpatients. It was detected in 4% of nasal samples, 0.7% of pharyngeal samples, and 1% of digital samples from the 288 hospital staff members. From the environment, MRSA was detected from hospital rooms of the surgery and neurosurgery wards, the nursing room and corridors of the obstetrics and gynecology ward, and the recovery room of the urology ward. The coagulase type of the MRSA obtained was the primarily type II regardless or whether the samples were obtained from the subjects or the environment. Concerning the drug sensitivity, many MRSA strains were highly resistant to DMPPC and FOM, but the sensitivity to RFP was 0.1 microgram/ml or less in all strains except for one highly resistant strain (200 micrograms/ml or above).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293221 TI - [Maternal carriage and vertical transmission of group B Streptococcus (GBS)]. AB - The pneumonia, sepsis and meningitis are common diseases of GBS infection in infants. There are early-onset and late-onset types in this disease, the result of the infection is unknown. M. Sugiyama reported that M9 is a new type of GBS in Japan in 1989. Analysis of GBS typing and serum specific antibody concentrations of the type are simple with new technics. By studying the infants' contamination we discovered that GBS appeared to originate from mother-infant sources. The infants were followed for a year. 52% of the infants had GBS contamination in their throat or stool. The most common type was Ia, followed by III, JM9 and NT6. Those types without III type had been present for more than 9 months in the infant. The contamination term of Ia or III type in infants correlated with the blood specific antibody concentration of the type. PMID- 1293222 TI - [Bacteriological study of traveller's diarrhoea. 4) Isolation of enteropathogenic bacteria from patients with traveller's diarrhoea at Osaka Airport Quarantine Station during 1984-1991]. AB - During the last 8 years (1984 to 1991), 16,639,233 overseas travellers were quarantined at Osaka Airport Quarantine Station and 38,326 travellers reported that they were (or had been) suffering from diarrhoea. Bacteriological examination of stools from 12,573 persons revealed the following results. 1) Various enteropathogenic bacteria were isolated from 3,669 cases (29.2%) examined. The predominant species of bacteria isolated were as follows: Salmonella, 1049 cases; Plesiomonas shigelloides, 1030 cases; Vibrio parahaemolyticus, 789 cases; Shigella, 607 cases; enterotoxigenic Escherichia coli, 422 cases; Vibrio cholerae non-O1, 212 cases. 2) There were no apparent seasonal variations in the isolation rate of these pathogens. 3) The suspected regions for infection with these pathogens were as follows: a) Salmonella, Enterotoxigenic E. coli and Plesiomonas, mainly South-East and South-West Asia. b) Shigella, South-West Asia, especially India (59.8%). c) V. parahaemolyticus and V. fluvialis, mainly South-East and East Asia. d) V. cholerae non-O1, V. mimicus, almost restricted to Asia, mainly South-East Asia. 4) 22 strains of V. cholerae O1 were isolated and 19 were Ogawa, E1 Tor. Of these strains, 13 were cholera toxin-producing strains and 9 were non-toxigenic strains. 5) Several pathogens (mixed infection) were isolated simultaneously from 670 cases. 6) The 1247 Salmonella strains were identified into 98 serovars. 7) Of 624 Shigella strains isolated, 57.9% were S. sonnei, 29.2% were S. flexneri, 8.6% were S. boydii, 4.3% were S. dysenteriae. 8) The most predominant serovar of V. parahaemolyticus was O4:K8. Of 1,247 strains isolated, 9.8% were not producing thermostable direct hemolysin (TDH). 9) 570 (91.3%) of 624 Shigella strains and 409 (32.8%) of 1,247 Salmonella strains isolated were resistant to any one of the drugs tested (SM. CP. TC. KM. ABPC. NA. OFLX). The resistance rate and the number of multiple drug-resistance strains increased year by year. 10) Enterotoxigenic E. coli was isolated from 422 cases (10.7%) of 3,939 cases. Cases with enterotoxigenic E. coli strains producing ST (heat-stable), LT (heat-labile) or both ST and LT were 53.8%, 24.2% and 14.2% respectively. The others were cases with mixed types of enterotoxin production. PMID- 1293223 TI - Staphylococcus aureus bacteremia in patients with hematologic disorders. AB - During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients. PMID- 1293224 TI - [Infectious complications in patients with adult T-cell leukemia]. AB - Between January, 1982, and January, 1992, a total of 112 patients with adult T cell leukemia (ATL) and 109 patients with non-Hodgkin's lymphoma (NHL) were admitted to our hospital. They were studied for their infectious complications. Infectious complications were seen in 90 patients (80.4%) with ATL, and 51 patients (46.8%) with NHL (p < 0.001). Documented infections were seen in 70 patients (62.5%) with ATL, and 30 patients (27.5%) with NHL (p < 0.001). Pneumonia (p < 0.005), skin infections (p < 0.05), Pneumocystis carinii pneumonia (p < 0.05), fungal infections (p < 0.05), cytomegalovirus infections (p < 0.05) and herpes simplex virus infections (p < 0.01) were identified infections at high risk for patients with ATL. Tuberculosis, listeriosis and salmonella infections were seen only in patients with ATL. PMID- 1293225 TI - [Detection of intestinal parasites from dogs in Tochigi-City in 1979 and 1991]. AB - To clarify whether sanitary and hygienic conditions surrounding humans and pet animals have improved or not, we examined feces from dogs for intestinal parasites in Tochigi in 1979 and 1991. Intestinal parasites were detected from 109 of the 262 dogs (41.9%) in 1979 and 86 of the 260 dogs (32.8%) in 1991. Among the parasites. Ancylostoma caninum, Tirchuris vulpis and Toxocara canis were most commonly detected, and their detection rates were higher in 1979. On the contrary, Dipylidium caninum, Strongyloides stercoralis, Isospora spp., which are important causes of human diseases, were detected at higher rates in 1991. In the dogs of outdoor feeding, the detection rates of parasites were markedly decreased, but slightly increased in the dogs of indoor feeding in 1991. These results suggest that sanitary conditions surrounding pet animals have not been sufficiently improved, in spite of the fact that humans are in more contact with their pet animals. PMID- 1293226 TI - [Comparison of polymerase chain reaction and IDEIA Chlamydia in detection of Chlamydia trachomatis from first-voided urine of male urethritis patients]. AB - We have reported a method for detection of Chlamydia trachomatis by polymerase chain reaction (PCR) with two oligonucleotides based on sequences within the major outer membrane protein gene from C. trachomatis serovar L2. In the previous report, in addition to treatment of the mixture of first-voided urine (FVU) sediment and 1 ml of urine with proteinase K. DNA purification by phenol extraction was necessary for preparation of template DNA for PCR. In this study, FVU sediment was suspended in 1 ml of Chlamydiazyme dilution buffer and a part of the suspension was treated with proteinase K for DNA extraction. The DNA extraction solution could be used as template for PCR without purification of DNA by phenol extraction. One hundred FVU specimens obtained from male urethritis patients were examined with the two methods (PCR and IDEIA) for detection of C. trachomatis. In 33 of 100 specimens, the DNA fragments of C. trachomatis was amplified by the PCR and in 32 of 100, the chlamydial antigen was detected by IDEIA. The positive and negative coincidence rate of the PCR to IDEIA were 93.8% (30.32) and 95.6% (65/68) respectively, resulting in a high overall coincidence rate at 95%. Thus, the improved method with PCR using FVU as a specimen is proved to be a useful, non-invasive diagnostic tool for diagnosis of chlamydial urethritis. PMID- 1293227 TI - [Nested polymerase chain reaction for the diagnosis and follow-up of tuberculous meningitis: a case report]. AB - We presented a case of tuberculous meningitis in which a nested polymerase chain reaction was useful for its rapid diagnosis and follow-up. A 5-month-old girl was hospitalized for gastrointestinal complaints of 4 days' duration. She initially had no meningeal signs, but showed a bulging of the anterior fontanel on the 10th day of her illness. Cerebrospinal fluid examination revealed a cell count of 886/3 microliters (80% lymphocytes), protein of 20 mg/dl, and glucose of 27 mg/dl. Tuberculous meningitis was suspected clinically and an antituberculous therapy was commenced on the 13th day. Although repeated attempts to culture Mycobacterium tuberculosis were negative, the DNA of the organism was detected sequentially from the cerebrospinal fluid of the 13th and 16th day by the method of a nested polymerase chain reaction. The final diagnosis of tuberculous meningitis was established on the basis of the positive results of the nested polymerase chain reaction, a positive tuberculin test, and typical cerebrospinal fluid findings. She recovered rapidly in response to the therapy and was discharged from the hospital without any neurological sequelae on the 89th day. The follow-up samples of the nested polymerase chain reaction resulted as negative after the 26th day of the illness. PMID- 1293228 TI - [A case of adult respiratory distress syndrome likely due to measles and Mycoplasma pneumoniae]. AB - We described a case of adult respiratory distress syndrome (ARDS) likely due to measles and Mycoplasma pneumoniae. A 24-year-old, previously healthy man was referred to our hospital because of respiratory arrest. He was unconscious and cyanotic. He had erythematous and polymorphic eruptions of his extremities and trunk, but his face was spared. His chest roentgenogram showed consolidation with air bronchograms affecting the whole bilateral lungs. After mechanical ventilation with positive end-expiratory pressure and administration of intravenous hydrocortisone and protease inhibitor "urinastatin" and so on, the patient recovered from his critical condition. No attributable organisms were isolated from the specimens investigated in his acute phase. Serological examinations of the specific IgM antibody to measles during the course indicated a recent measles infection. Mycoplasma pneumoniae indirect hemagglutination test rose from a titre of less than 1/40 to 1/60. ARDS is a rare complication of measles or Mycoplasma pneumoniae infection. Moreover he received measles vaccine before 1970 in Japan, so this case was suspected to be atypical measles. PMID- 1293229 TI - Ophthalmic drug use in the OR. AB - Categories of ophthalmic drugs used in the operating room (OR), their generic and trade names, indications for use, actions, contraindications, usual dosages, adverse reactions, and nursing concerns are presented to give the ophthalmic nurse a comprehensive knowledge of the most commonly used ocular pharmaceuticals. PMID- 1293230 TI - QA, CQI, TQM: what's the difference? AB - Total Quality Management (TQM) is not a program, but a process. It is a major cultural change of healthcare organizations. TQM should not be embraced as a "short term fix," but as the long term solution to the shortcomings in the delivery of patient care. PMID- 1293231 TI - Microwave ovens and eye injuries. PMID- 1293233 TI - Standards of clinical nursing practice. PMID- 1293232 TI - Back to the basics. PMID- 1293234 TI - A generation gap? PMID- 1293235 TI - Nurses: advocates for nursing. AB - Based on the nursing literature and my own ophthalmic nursing experience, there appears to be some confusion about how the general public, our colleagues, and physicians view the duties and responsibilities of the profession of nursing. We, as nurses, can serve as advocates for our own profession and educate the public about who we are, how we have achieved our current status and goals, and where we expect to be in the future. PMID- 1293236 TI - Oral colon transit scintigraphy using indium-111 DTPA: variability in healthy subjects. AB - Oral colon transit scintigraphy using indium-111 diethylene-triamine-pentaacetic acid was performed in 41 healthy subjects (22 females, 19 males) to determine variability with age and sex and to define normal ranges. Repeat studies were performed in 10 females and 9 males to assess intra-subject variability. Females showed slightly but significantly slower colonic transit than men and slightly greater intra-subject variability. There was no correlation between age and colonic transit. The results have implications for the definition of normal ranges. PMID- 1293237 TI - Electromyography of the pubococcygeus muscles in patients with obstructed defaecation. AB - The function of the pubococcygeus muscles during defaecation straining was compared in 10 women with obstructed defaecation and 12 age-matched control subjects. Video-proctography in each patient showed failure to evacuate the rectum and sagging of the pelvic floor during attempted defaecation. Trans perineal concentric needle electromyography in the puborectalis muscle and transvaginal electromyography in the pubococcygeus muscle was carried out during defaecation straining and during attempted rectal balloon expulsion. Contraction of the pubococcygeus muscle was observed in 10 of the 12 control subjects and in 2 of the 10 patients with obstructed defaecation (P < 0.005). Virtually equal proportions of subjects in each group showed relaxation or contraction of the puborectalis muscle during straining. There was significant perineal descent on straining in the patient group (P = 0.005). This group of patients with obstructed defaecation showed failure of the pubococcygeus muscles to contract, perhaps due to neuropathic weakness of the muscles. The puborectalis muscle did not cause obstructed defaecation in these patients, and the concept of "paradoxical" contraction of this muscle is questioned. PMID- 1293238 TI - Conservative and surgical treatment in acute and chronic anal fissure. A study on 308 patients. AB - The aetiology of anal fissure is not fully understood--why some heal spontaneously and others become chronic remains a mystery. In this study we compared surgical and conservative therapy and investigated which surgical procedure is most useful in the treatment of fissure. There were investigated 308 patients, 157 with acute fissure and 151 with chronic fissure. Healing was achieved in 45 +/- 15 days and in 40 +/- 10 days in acute fissures treated conservatively and surgically, respectively, 40 +/- 15 days and 30 +/- 5 days were required to achieve healing in chronic fissure by conservative and surgical therapy, respectively. Manometric tests showed a decrease in resting pressure and maximum voluntary contraction pressure at one month, and an increase towards the pre-operative level at 4 months for both parameters. There were no recurrences at 5 years in 100 patients (50 males and 50 females). PMID- 1293239 TI - Combined radiation and chemotherapy for epidermoid carcinoma of the anal canal. AB - Between 1985 and 1992, 46 patients with epidermoid carcinoma of the anal canal were treated prospectively by a protocol of combined radiation and chemotherapy with 5-Fluorouracil and Mitomycin C. The survival rate, NED-survival rate and local tumour control rate were 84%, 71% and 83% at 5 years. Anorectal function was retained in 33 of 41 patients (80%). We observed severe acute toxicity including three deaths, but very little late morbidity. The only marginally significant prognostic factor (P = 0.06) for local tumour control was T-stage. NED-survival was significantly affected (P = 0.02) by reduction of chemotherapy during the second course. PMID- 1293240 TI - Observations on the characteristics of stimulated defaecation in severe idiopathic constipation. AB - A combined manometric and radioisotope study is described which was designed to investigate the motility characteristics of induced defaecation in the colon, rectum and anal canal, in patients with severe constipation. Five women with severe idiopathic constipation, aged 30-45 years, were studied. A multiple channel water-perfused manometric tube was placed colonoscopically into either the whole colon or left colon to monitor pressure activity. In two whole-colon studies, 5.5 MBq 111In DTPA and later 9 MBq 99mTc DTPA were instilled into the colon to monitor the transit of colonic contents in response to two separate stimuli. Motor activity was initiated on both occasions by intraluminal instillation of 5.5 mg bisacodyl. In the whole-colonic studies a right colonic stimulus initiated multiple high-pressure peristaltic waves which traversed the entire length of the colon. The bowel was then refractory to a second stimulus at the splenic flexure. In the five left colonic studies, a stimulus at the splenic flexure produced high-pressure peristaltic waves which proceeded distally, and which included a rise in rectal pressure. The anal canal relaxed simultaneously with the onset of peristalsis high in the left colon, and remained relaxed until the pressure wave reached the anus and bowel content had been expelled. In both types of study high-pressure waves corresponded to the effective transport of radioisotope. The constipated patients showed a coordinated motor response to the stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293242 TI - Preoperative hyperthermia combined with chemotherapy and radiotherapy for patients with rectal carcinoma may prevent early local pelvic recurrence. AB - We examined retrospectively the results of hyperthermia combined with irradiation and chemotherapy (HCR) prescribed preoperatively for patients with adenocarcinoma of the rectum. We compared two groups of patients: Group A: 23 were treated surgically between 1986-1988 and received HCR therapy; group B (controls) 48 were treated with surgery alone or surgery plus chemotherapy from 1980-1985. The recurrence rate within 2 years was compared. Although there was a difference in follow-up time, the two groups were comparable with regard to various prognostic factors. The incidences of local recurrence and of lung metastasis were nil in those given the HCR therapy. In group B, however, the incidences were 15% and 10%, respectively. These differences were statistically significant (P < 0.05). The incidence of liver metastasis was much the same between the two groups. All patients tolerated the HCR therapy well except for one with myelosuppression and who refused local hyperthermia because of mild anal pain. There were no other side effects requiring cessation of this treatment. These findings suggest that preoperative HCR therapy for patients with rectal carcinoma decreases the frequency of local recurrence and the likelihood of tumour cell spread during surgical procedures. PMID- 1293241 TI - Reduction of the effluent volume in high-output ileostomy patients by a somatostatin analogue, SMS 201-995. AB - Twelve ileostomy patients were given subcutaneous SMS 201-995 therapy (100 micrograms t.d.s. for 5 days) in a randomized placebo-controlled trial. All patients had ileostomies constructed 60 cm proximal to the terminal ileum (proximal ileostomy) following restorative proctocolectomy. SMS 201-995 reduced the daily ileostomy output from 997 +/- 52 g to 736 +/- 28 g, P < 0.05, along with a decrease in daily sodium and chloride excretion (sodium: 92.60 +/- 8.51 to 75.22 +/- 8.64 mEq, chloride: 143.46 +/- 8.54 to 113.60 +/- 15.84 mEq; both P < 0.05). There were no significant changes in the plasma levels of glucagon, C peptide, insulin, renin or aldosterone with SMS 201-995 therapy. Patients developed no severe side effects and reported easier management of the ileostomy and a reduction in thirst. Our results suggest a possible clinical role for SMS 201-995 in the management of proximal ileostomy. PMID- 1293243 TI - Anal fistulas in Crohn's disease: incidence and outcome of surgical treatment. AB - The incidence and prognosis of anal fistulas were investigated in a prospective study comprising 136 patients operated on for Crohn's disease. The incidence of anal fistulas was 27 of 136 (20%), in patients with classical disease 12 of 68 (18%), and in those with Crohn's colitis 15 of 68 (22%). A fistula preceded the intestinal manifestation of the disease in 6 patients. At the time of diagnosis of Crohn's disease anal fistulas were observed in 19 cases, including 3 of the 6 with early onset which had resisted treatment and remained active. Five patients developed anal lesions during the course of the disease, all but 2 in temporal relationship to an intestinal recurrence. Of the 27 patients with anal fistulas, 11 were of the low-anal type, whereas 14 were anorectal. Conventional laying open of the fistula was undertaken in all patients with classical Crohn's disease in close conjunction with resection of the intestinal disease. On local surgical treatment 10 of 12 (89%) healed with preservation of continence. Four recurrent fistulas occurring in conjunction with intestinal recurrence also healed uneventfully. Laying open was undertaken in 11 of the 15 patients with colitis. Healing was obtained in only 4 of these patients. In the remaining 4 severe colitis indicated immediate proctocolectomy. Occurrence of fistulas involved a significant delay in perineal healing after proctectomy. It is concluded that traditional laying open of an anal fistula in patients with classical Crohn's disease is followed by high rate of uneventful healing. In contrast, local surgical treatment of anal fistulas complicating Crohn's colitis is usually unsuccessful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293244 TI - Proctological outpatient surgery. PMID- 1293246 TI - Reduced pouch capacitance due to gynaecological pathology. PMID- 1293245 TI - A simple technique for sutureless very low colorectal anastomosis. PMID- 1293247 TI - Double versus single stapling technique in rectal anastomosis. PMID- 1293248 TI - Prevention and treatment of osteoporosis. One of the most frequent disorders in American women: a review. AB - This review summarizes basic pathophysiology, epidemiology, classification and theories on the etiology of osteoporoses. Diagnostic, preventative and therapeutic aspects are discussed including the use of hormones and hormone analogues (estrogen, progestins, calcitonins, anabolic steroids), calcium, fluoride, bisphosphonates, vitamins D and their metabolites and the recently proposed "coherence therapy". Reference is made to new compounds under study including imidazoquinazolinones, methylxanthines and benzothiophenes. PMID- 1293249 TI - A statistical study on clinical findings of solar keratosis. AB - Clinical findings were studied in 50 patients with 53 lesions of solar keratosis encountered during the 15 year period from 1977 to 1991. The majority of these cases were evident in the over-sixty age group (average 62.2 years). A greater proportion were females. Most lesions were observed on the face; especially on the cheek, and from the outer eyelid to the temple. The erythematous type (desquamative-keratotic) lesion was the most evident. With the exceptions of the years 1979 and 1991, no remarkable increase in the number of patients was noted during the 15 year period. PMID- 1293250 TI - A statistical study on histopathologic findings of solar keratosis. AB - We examined histopathologic data from 50 patients with 53 lesions of solar keratosis encountered over the past 15 years (1977 to 1991). The epidermis showed acanthosis, uneven epidermal dyeing properties, disorderly arrangement of the basal cells, atypia of the nucleus, mitotic figures and hyperpigmentation of the basal layers. The dermis showed actinic elastosis, cell infiltration mainly consisting of the lymphoid cells, and incontinentia pigmenti histologica. Among histologic types, the hypertrophic type was the primary example. PMID- 1293252 TI - Treatment of chronic cerebrovascular disease in elderly patients with pentoxifylline. AB - A placebo-controlled, randomized, double-blind study was conducted to assess the efficacy and safety of pentoxifylline in 80 patients with symptoms of vascular dementia. Efficacy was assessed using neuropsychologic tests. With regard to the primary efficacy criteria, absolute changes in the active treatment group were more pronounced in both the protocol and endpoint analysis than in the placebo group. Compared with the placebo group, differences were statistically significant for the active treatment group. Similar changes were reported in a post-hoc defined subgroup of patients displaying "stepwise deterioration," an essential criterion of multi-infarct dementia (MID). Medication was generally well-tolerated. The present study shows that pentoxifylline is suitable for the symptomatic treatment of vascular dementia. PMID- 1293251 TI - Relation between serum uric acid and angiographically defined coronary artery disease in postmenopausal women. AB - Serum uric acid (UA) levels were studied in 40 postmenopausal women and 57 men, almost matched for age and body mass index (BMI) and undergoing coronary angiography. For women, the mean value of UA increased as the number of coronary arteries with > or = 50% stenosis increased. Its value was significantly higher (p < 0.05) in a three-vessel disease group than that of a group without stenosis. No significant changes were seen in men. However, the increase in UA for postmenopausal women was statistically (p < 0.05) correlated with serum triglyceride levels. Possibly, UA is not an independent coronary risk factor. However, elevated UA levels may suggest the prevalence of severe coronary artery stenosis for postmenopausal women. PMID- 1293253 TI - Serum levels of lipids and apolipoproteins in angiographically assessed coronary artery disease in Japanese patients. AB - Serum total cholesterol (T-CHO), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo A-I, A-II, B, C-II, C-III and E) values were determined in 143 Japanese subjects undergoing coronary angiography. Among the factors measured, T-CHO, TG, apo B and C-III levels were significantly higher in patients with coronary artery disease (CAD) than in those without CAD. The HDL-C/T-CHO ratio was also significantly lower in patients with CAD. Although no parameters show differences between the group without CAD and the group of single vessel disease, T-CHO and apo B were significantly higher in the groups with double and triple vessel disease, and TG and apo C-III were also higher in the group with triple vessel disease compared with the normal group. Furthermore, the HDL-C/T-CHO ratio was significantly lower in the double and triple vessel groups, and HDL-C was lower only in the triple vessel group. The results indicate that changes in these parameters suggest a high likelihood of multiple vessel disease, and that an increase in TG and apo C-III levels is also one of the important indicators for CAD even in Japanese patients. PMID- 1293255 TI - Helicobacter pylori and peptic ulcer diseases: prevalence and association with antral gastritis in 210 patients. AB - Evidence is accumulating that Helicobacter pylori infection plays a major contributory role in peptic ulcer disease [Duodenal Ulcer (DU) and Gastric ulcer (GU)] and non-ulcer dyspepsia (NUD). We, therefore, studied prospectively 210 consecutive patients with upper gastrointestinal symptoms (62 DU, 38 GU and 110 NUD) to determine the prevalence of H. pylori infection and to investigate their association with histological gastritis. Using endoscopic biopsy of the gastric antrum for diagnosing H. pylori infection by Campylobacter-like Organism (CLO) test, histology or bacteriology, the overall prevalence of H. pylori was 63.3 per cent. When H. pylori infection was related to diagnosis, DU had the highest prevalence rate of H. pylori infection (66%), GU and NUD were less frequently associated with H. pylori infection (55% and 44% respectively). We found a close association between H. pylori infection and histologically antral gastritis, in that 72.7, 61.7, and 62.6 per cent of the DU, GU and NUD patients with antral gastritis (respectively) had H. pylori infection. In contrast, none of these patients seen with normal antrum had H. pylori infection. We also found that the prevalence of H. pylori in our patient series was not age related. Of the three procedures used to demonstrate H. pylori, the CLO test and histological staining method gave the highest yields of 84.9 and 79.6 per cent respectively, and bacteriology in only 44.3 per cent, we conclude that the prevalence of H. pylori infection in Thai patients with upper gastrointestinal symptoms is high. H. pylori infection commonly occurs in the patients with antral gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion. PMID- 1293254 TI - Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators. AB - Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism. PMID- 1293256 TI - The impact of routine preoperative electrocardiogram in patients age > or = 40 years in Srinagarind Hospital. AB - A 12 lead electrocardiogram (ECG) has been recommended for adult patients before operations involving general or regional anesthesia. However, there is a growing consensus that it is of little benefit and ECG should be done only in selected subsets of patients with cardiac signs and symptoms or older patients. We prospectively surveyed 1,013 patients before operation, 395 patients were 40 years or more, ECG abnormalities were present in 130/395 (32.9%), significant ECG abnormalities in 31/395 (7.9%) and ECG with management change in 10/395 (2.5%). Old or questionable myocardial infarction were found in 8 (4.0%) and acute ischemia or injury in 4 (2.0%). The frequency of ECG abnormalities increased with age in males but not in females. Abnormal physical examination could predict only 20 per cent of abnormal ECG. The variables which could predict ECG abnormalities were age and irregular pulse. The frequency of ECG abnormalities, significant ECG abnormalities and ECG abnormalities which led to management change in those patients with normal physical examination were 31.7, 6.4 and 2.2 per cent respectively. In conclusion we propose that preoperative ECG may be indicated in both men and women aged > or = 40 years. PMID- 1293257 TI - Gore-Tex cruciate ligament reconstruction in athletes. AB - This prospective study evaluated the athletes with chronic instability of the knees using the expanded polytetrafluoroethylene (PTFE) prosthetic ligament as a substitute for the ACL and PCL preoperatively and at regular intervals during the post-operative period. Thirty Gore-Tex ACL and four Gore-Tex PCL reconstruction were performed. All patients had chronic instability of the knee joint for a duration of one month to five years (average 15.7 months). There were thirty-one males and three females, most of them were football players (63%). The average follow-up was 23 months postoperation. Ninety-seven per cent of the patients had satisfactory results. Objectively the instability pattern was improved in 97 per cent of the knees and subjectively, no pain persisted post operatively. Rejection occurred in one patient. The results indicated excellent stability of the affected knee joint. However, longevity of the prosthesis under the wide variety of loading conditions in athletes remains to be determined by continuing clinical study. PMID- 1293258 TI - A common source foodborne outbreak of E1 Tor cholera following the consumption of uncooked beef. AB - In July 1988, an outbreak of cholera with 71 culture-confirmed cases of biotype El Tor, serotype Ogawa, occurred in a non-endemic area in Mae Sot district, Tak province. Fifty-two cases had diarrhea and 19 had asymptomatic cholera infection. No cases died. Epidemiological investigation revealed a significant association between cholera infection and the consumption of uncooked beef. Increased risk of cholera infection was observed when the incriminated beef was kept at room temperature and consumed later without cooking. The beef was possibly contaminated with V. cholerae O1 from an infected butcher who may have contracted the disease from his foreign worker who was found to have asymptomatic cholera infection. Early detection of the outbreak and rapid identification of transmission source permitted prompt appropriate control measures which, therefore, prevented the outbreak from spreading to other communities. As outbreaks of foodborne diseases, including cholera, have been reported frequently after the consumption of raw food in many parts of Thailand, preventive educational efforts should be directed towards modifying the traditional behavior patterns of consuming raw food among these Thai people. PMID- 1293259 TI - Elderly bed-blockers in a Thai teaching hospital: is it a problem? AB - Elderly patients suffer from a wide range of chronic disabling diseases and social problems. These conditions often lead to increased lengths of hospital stay for acute medical and surgical problems--"bed-blocking". By means of a one day census of all inpatients at Chulalongkorn Thai Red Cross Hospital the number and reasons for continued hospital stay of all patients, classified by age (less than 60, and 60+ years), were measured. Of 191 medical inpatients surveyed, 34 per cent were 60 years and over. More older than younger patients were still in hospital for non-medical reasons (35% vs 21%, Chi-square = 4.89, p < 0.01). Durations of hospital stay were longer for older patients: median stay 8 and 11 days respectively for those less than 60 and those 60+ years. Early discharge of disabled elderly people to their families was achieved by vigorous social work, thus reducing the extent to which elderly patients become bed-blockers. Further demographic trends, coupled with a breakdown of the extended family structure, will make bed-blocking a very likely problem. The present patterns of care may lead to poor long-term outcomes for the elderly. PMID- 1293260 TI - Corneal involvement in acrodermatitis enteropathica: a case report. AB - A case of acrodermatitis enteropathica occurred with corneal changes consisting of superficial punctate lesions, nebulous subepithelial opacities and linear epithelial erosions. These manifestations exacerbated intermittently whenever the patient ran out of her oral zinc sulphate therapy, but regressed and disappeared when she resumed her medication. PMID- 1293261 TI - Direct epidural morphine injection during lumbar discectomy for postoperative analgesia. AB - A double-blind controlled study was done on 42 patients to test the analgesic activity of epidural morphine after lumber laminectomy for single level disc herniation. Sixteen patients received 3 mg preservative-free morphine. Twenty-six patients received normal saline. The patients given epidural morphine had a longer postoperative pain-free period (6.28 vs 2.37 hours) and needed less postoperative analgesia (0.2 vs 0.9 times for paracetamol, and 0.16 vs 0.51 times for morphine). Epidural morphine injection under direct vision during discectomy operation is an effective and safe method for postoperative pain relief. PMID- 1293262 TI - Scanning electron microscopic study on dendritic cells and fibroblasts in connective tissue. AB - Perfusion fixation and intravascular resin injection were used to study in situ the cells of superficial fascia (loose connective tissue) of the rat limb by scanning and transmission electron microscopy. These procedures enabled us to differentiate fibroblasts, representative cells of the connective tissue and so called "dendritic cells," the other cellular constituent of the tissue, known as possible antigen presenting cells. "Dendritic cells" were amoeboid with some spatular processes by which the cells clung to the collagen fiber bundles. The fine structures characteristics of macrophages; they contained abundant primary and secondary lysosomes and expressed factor XIIIa in their cytoplasm. Fibroblasts, on the other hand, were attenuated, sheet-like cells whose edges were juxtaposed closely to collagen and elastic fibers, and were further anchored by microfibrils. The cells were usually interconnected to each other with gap junctions, thus producing a cellular network in the connective tissue. PMID- 1293263 TI - Ultrastructure of intracellular membranous system and intracellular transport of asialoglycoproteins in rat hepatocytes. AB - The ultrastructure of the intracellular membranous system in rat hepatocytes was observed three dimensionally with a scanning electron microscope using the aldehyde prefix osmium-dimethyl sulfoxide-osmium method. Intracellular organelles were clearly observed in three dimensions, and direct connection of tubular structures with the bile canalicular membrane was clearly seen. The transcellular pathway of asialoglycoproteins in isolated cultured rat hepatocytes was also investigated, by affinity cytochemistry, using gold-conjugated asialofetuin, under a transmission electron microscope. Gold particles were clearly seen not only in vesicles, endosomes and lysosomes, but also in the tubular structures. These results suggest that the tubular structures in rat hepatocytes directly participate in the transcellular transport of macromolecules. In addition, the frequent connections of tubular structures with the bile canalicular membrane indicate that these structures around the bile canaliculus may supply membrane components to the bile canalicular membrane. PMID- 1293264 TI - Immunogold localization of ribulose-1,5-bisphosphate carboxylase/oxygenase in developing proplastids of dark-grown wax-rich cells of Euglena gracilis. AB - Wax-rich cells of Euglena gracilis Z grown in the dark without agitation were subjected to freeze-substitution procedures in electron microscopy, which gave intact images of wax accumulated as globules in the cytoplasm. The proplastids in these wax-rich cells were shown to contain no extensive internal structures. When these cells were transferred to an inorganic medium containing ammonium salt and aerated in the dark the specific activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) increased concurrently with the development of a prolamellar body and a rudimentary pyrenoid. When cell sections were labeled with antisera prepared against RuBisCO subunits followed by protein A-gold, gold particles (RuBisCO) were localized in a narrow peripheral region between the plastid envelope and the prolamellar body during an earlier phase of the dark incubation of cells. Subsequently, immunogold particles were concentrated over the rudimentary pyrenoid formed at a site adjacent to the prolamellar body, while the stroma was only slightly labeled with gold particles. It was postulated that the small subunits of RuBisCO made in the cytoplasm combined with the plastid made large subunits to form the holoenzyme at the peripheral region near the prolamellar body before transfer to the rudimentary pyrenoid. PMID- 1293265 TI - Scanning electron microscopy of proteoglycans in metaphyseal cartilage. AB - Alcian blue (AB) was used for scanning electron microscope investigations on metaphyseal cartilage. In the pericellular area three-dimensional network connecting the cell membrane surface to the lacunar wall is evident. The network is formed by very long rod-like filaments about 50 nm thick. The segments may be interpreted as the proteoglycans (PGs) of the pericellular area. In the pericellular area in hypertrophic and degenerative zones, the rod-like segments are closely connected to "chain granules" which are the morphological expression of Ca-P non crystalline compounds. The rod-like segments are not at all evident either in glutaraldehyde-osmium fixed fragments or in predigested-(streptococcal hyaluronidase and chondroitinase) AB stained ones. It is concluded that AB is a good method to detect the three-dimensional spatial disposition of cartilage PGs. PMID- 1293266 TI - Natural surfactant for neonatal respiratory distress syndrome in very premature infants: a 1992 update. AB - Natural surfactant (Surfactant TA, Survanta, CLSE, SF-RI 1, Curosurf and human surfactant obtained from amniotic fluid) therapy for RDS in very premature infants has been evaluated in 17 controlled clinical trials. Uniformly intratracheal surfactant administration caused a decreased intensity of mechanical ventilation during the first hours (reduced inspiratory pressure, reduced oxygen requirements) as an immediate effect of surfactant administration. Metanalysis reveals barotraumatic pulmonary complications mainly, pneumothorax and pulmonary interstitial emphysema to occur less frequently in surfactant treated infants in virtually all trials; an increased incidence of survival without bronchopulmonary dysplasia following surfactant treatment was observed in 10 controlled clinical trials. The incidence of other complications of prematurity (intracranial hemorrhage, patent ductus arteriosus and necrotizing enterocolitis) was unchanged following natural surfactant treatment. Dosing of natural surfactant is still under investigation, however recent data indicate that the initial dose should not be less than 100 mg/kg b.w. and retreatment should be given to infants with unsatisfactory response (i.e. fraction of inspired oxygen (FiO2) > 40%). Timing of surfactant treatment still remains controversial. Prophylactic treatment shortly following birth has been compared with rescue-treatment, i.e. surfactant administration to infants suffering from manifest RDS in most studies 4-8 h after birth. Conflicting data from 5 controlled trials may be interpreted as follows: prophylactic treatment seems to be favourable for extremely premature infants (GA < or = 26 weeks) and rescue treatment seems to be adequate for infants of 27-30 weeks of gestation. Intratracheal surfactant instillation in very premature infants did not result in an improved lung function for 24 h to 48 h in all patients. Ten--25% of study infants were reported to be "non-responders", i.e. infants without sustained decrease in oxygen requirements (i.e. FiO2 > 40%). Various factors may be operative including congenital bacterial infections (sepsis or pneumonia), lung hypoplasia and cardiac failure. Inactivation of surface properties of natural surfactant caused by a leakage of proteins across the alveolar-capillary membrane was observed in experimental and clinical studies. Current investigations focus on a combination of postnatal steroids and surfactant treatment to improve lung function and outcome in "non-responders". As long as any controlled clinical studies are being published, this approach remains experimental. Up to now, any controlled clinical trials have been performed to assess different modes of artificial ventilation (e.g. high frequency oscillating ventilation versus conventional ventilation) combined with surfactant therapy. Data obtained from premature animals given natural surfactant indicate any advantage with respect to gas exchange and lung histology to result from high frequency ventilation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293267 TI - Protein C activity in severely ill newborns with congenital heart disease. AB - Levels of protein C functional activity were studied in twenty-nine full-term infants with symptomatic congenital heart disease, who presented in the neonatal period. Protein C levels on admission ranged from < 10% to 61% (mean 37.7% S. D. 14.1%). Eight of the twenty-nine babies had protein C levels between 1.5 and > 3.0 S. D. below the normal neonatal mean with no parental evidence of familial deficiency. Of these infants with low protein C two developed thrombotic complications and four had evidence of coagulation factor consumption. Critically ill infants were over-represented in the group with low protein C. Severely ill newborn infants with protein C at or below the lower limit of the normal neonatal range may be at increased risk of either a consumptive coagulopathy or major thrombosis. PMID- 1293268 TI - Onset of spontaneous labor and changes in E2 and progesterone levels--possible interrelation. AB - Unlike the findings in animal studies, in which a decline in progesterone levels is clearly associated with the onset of labor, investigation of progesterone levels among human parturients has resulted in controversy. This study was designed to address the issue and evaluate labor-onset related changes of estradiol-progesterone (E2-P) concentration in fetal scalp serum, umbilical vein serum and in the peripheral maternal serum. Seven women in spontaneous labor, were compared to 7 women in whom labor was induced. Our results reveal a significant decrease in the maternal serum P concentration when spontaneous labor is taking place (120.6 +/- 24.5 mg/ml verus 177.3 +/- 61.4 mg/ml, p < 0.05). Significant change in the ratio of the fetal scalp to the maternal serum E2/P ratio in women at spontaneous labor versus induced labor is also shown. We could not demonstrate any changes in the E2 levels in relation to labor. We conclude that the onset of labor in human pregnancy is most probably preceded by local changes in the levels of P and ratio of P to E2. These changes may play an important regulatory role in onset of labor. PMID- 1293269 TI - Salbutamol infusion to treat neonatal hyperkalaemia. AB - Salbutamol infusion, 4 micrograms/kg in 5 ml of water infused for 20 minutes, was given to treat hyperkalaemia (potassium level > 6.0 mmol/l) in 10 critically ill preterm infants (median gestational age 26 weeks). Seven infants had acute renal failure, two had persistent metabolic acidosis without renal failure and the remaining infant had a combination of acute renal failure and persistent metabolic acidosis. No infant developed a tachycardia or became hyperglycaemic in response to the infusion. Seven of the 10 infants ultimately died but this was at a mean of 9 days following the infusion and as a consequence of complications due to their extreme prematurity or major congenital abnormality. In response to the infusion the potassium level fell in 7 infants with acute renal failure by a median of 1.1 mmol/l (range 0.7-1.8) at one hour but in the three infants with a persistent metabolic acidosis, the potassium level continued to rise. We conclude that salbutamol infusion achieves, without side-effects, at least a temporary reduction in hyperkalaemia in preterm infants with renal failure, but not metabolic acidosis. Its effect is of sufficient duration to allow ample time for definitive therapy to be instituted and thus may be a useful alternative for infants in whom the possible hypoglycaemic side-effects of glucose and insulin should be avoided. PMID- 1293270 TI - Increased inorganic sulfate concentrations in amniotic fluid. AB - We assayed inorganic sulfate by ion chromatography in 49 amniotic fluid samples from pregnancies of 14 to 38 weeks gestation. In second trimester samples (14 to 26 weeks gestation), amniotic fluid sulfate concentrations (317 +/- 22 mumol/L, mean +/- SE; n = 32) were not different from previously reported maternal serum values but were significantly lower (p < 0.001) than in the third trimester (693 +/- 42 mumol/L; n = 16). In third trimester samples, sulfate concentrations were significantly correlated with creatinine and uric acid but not chloride, suggesting that renal excretion may be the major source of the amniotic fluid sulfate in the late stages of gestation. PMID- 1293271 TI - Accelerated lung maturation following maternal steroid treatment in infants born before 30 weeks gestation. AB - A meta-analysis was performed of 9 controlled trials of maternal beta /dexamethasone treatment in which the incidence of RDS in infants born before 30 weeks gestation was reported. A significant decrease could be shown in 250 immature infants. The number of cases was to small for analysis of lower gestational ages or for the demonstration of a reduction in mortality. In a separate study of 135 infants born before 30 weeks gestation tracheal aspirate phospholipid analysis was performed using thin layer chromatography. 64 of them had been exposed prenatally to steroids. Significantly more of these infants had a mature L/S ratio > or = 2.7 (p < 0.02) and prenatal glucocorticoid treatment was associated with a markedly increased survival rate (odds ratio 2.4, p < 0.02). We conclude from the meta-analysis of the literature and from the findings of our study, that accelerated lung maturation follows prenatal steroid treatment with a reduction in RDS-incidence even in very immature fetuses. Consequently it would be appropriate to administer glucocorticoids combined with tocolysis since this has been shown to be beneficial for those women threatening to deliver prematurely at less than 30 weeks gestation. PMID- 1293272 TI - The effect of thyroxine and corticosteroids upon amniotic fluid fluorescence polarization: a randomized controlled study. AB - The efficacy of glucocorticoid and intra amniotic thyroxine therapy on fetal lung maturity were compared in a randomized prospective clinical trial. Eighty two patients received either intra amniotic thyroxine (n = 36), or intra muscular Dexamethasone (n = 46). The Fluorescence Polarization (FP) of amniotic fluid measured prior to and one week following treatment were similar in the two groups. The rate of decrease in FP value per unit of time (dFP/dt) was identical in the T4 and corticosteroid treated patients and the proportion of immature FP values obtained was similar in the two groups. The effect of thyroxine therapy was more pronounced in pregnancies above 33 weeks gestation. Intra amniotic thyroxine therapy appeared to be as effective as glucocorticoids for the enhancement of fetal lung maturity. This therapeutic modality may be of particular use on pregnant subjects in whom a relative contra indication for the administration of steroids exists. PMID- 1293273 TI - t-PA activity and antigen in the newborn and infant. AB - Concentrations of tissue plasminogen activator (t-PA) activity and t-PA antigen in blood obtained from neonates were investigated in order to elucidate a fibrinolytic condition of the neonates and compare with that of the infants and children. The t-PA activity was measured by bioimmunoassay using monoclonal antibody (SP-322), which bound with an epitope nonintervening with active site of t-PA. The t-PA antigen was detected by ELISA using the same monoclonal antibody (SP-322). As a result, t-PA activity in blood from the newborn baby increased to 0.97 +/- 0.48 IU/ml at the second to the fifth day, and decreased gradually to the baseline levels of healthy adult until 15 years old. The t-PA antigen level was increased from the seventh day. These results suggests that t-PA activity in blood from the neonates may be higher concentrations than those from the infants, children and adults. PMID- 1293274 TI - Computerised cardiotocography following vibro-acoustic stimulation. AB - To study the effect of vibro-acoustic stimulation (VAS) to the mean fetal heart rate (FHR), period of high and low FHR variation, overall variation (msec and bpm) and short term variation (msec). In a prospective study 17 pregnant women between 34-42 weeks gestation admitted to antenatal ward for obstetric complications two 60 min FHR recording was carried out with an interval of 30 min in between recordings. On a random basis the fetus was stimulated by a vibro acoustic stimulator for 5 sec at the beginning of one of the two 60 min FHR recordings. Automated analysis of the FHR, tocodynamometry, and maternal perception of fetal movements was done by a commercially available computerized programme (System 8000). It was possible to obtain the two 60 min recordings with signal loss of < 10% in 12 out of 17 patients. No changes were observed when the FHR parameters for 60 min after VAS was compared with the control period. When analyzed in segments of 0 to 10, 11 to 20, 20 to 40 and 41 to 60 min the mean baseline FHR was significantly higher after VAS during the first 10 minutes compared with any 10 or 20 min segment of the control period or any such segments 10 min after VAS. Concomitantly the overall variation and short-term variation was significantly lower during the first 10 minutes following VAS (p < 0.05) compared with the parameters in the corresponding periods during the control period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293275 TI - The predictive value of CRP and I/T-ratio in neonatal infection. AB - C-reactive protein (CRP) and immature: total neutrophil ratio (I/T-ratio) were evaluated as tests to detect neonatal sepsis in a prospective study in 185 neonates. The positive predictive values (P.P.A.) of CRP and I/T-ratio when used for screening for infection were 20-30% in early onset and 50-60% in late onset infection. In patients with clinical signs of infection the P.P.A. of CRP and I/T ratio was 35-45% in early onset and 65-70% in late onset infection. For the whole group of patients the negative predictive accuracy (N.P.A.) of both CRP and I/T ratio was high, in early as well as in late onset infection (90-98%). Based on incidence rates of 7.5% and 23% for early and late onset infection respectively the chance that the infant was not infected was already 92.5% and 77% for the two types of infection. In conclusion, CRP and I/T-ratio determination are of limited value as diagnostic tests in neonatal infection. PMID- 1293276 TI - Effects of n-alkanols and a methyl ester on a transient potassium (IA) current in identified neurones from Helix aspersa. AB - 1. A two-microelectrode voltage clamp was used to determine the effects of n butanol, n-hexanol, n-octanol, n-decanol and methyl hexanoate on a transient potassium (IA) current in identified Helix aspersa neurones. Experiments were carried out at a temperature of 10-12 degrees C. 2. Each n-alkanol reversibly reduced the amplitude of the IA current. Logarithmic dose-response curves for the current reduction by each homologue were sigmoidal and had slope factors of around four. The concentrations required to reduce the peak (with time) current at -30 mV by 50% (ED50 +/- fitted standard error) were: 57 +/- 5 mM (n-butanol); 2.0 +/- 0.1 mM (n-hexanol); 0.28 +/- 0.02 mM (n-octanol) and 0.016 +/- 0.001 mM (n-decanol). Methyl hexanoate also reduced the current amplitude, with an ED50 of 1-2 mM. The Helix IA current thus showed a similar sensitivity to n-alkanols to that of squid and rat sodium currents but was rather more sensitive than the squid delayed rectifier potassium current. 3. The n-alkanol ED50 concentrations were used to calculate a standard free energy per methylene group for adsorption to a site of action in the cell of -3.1 +/- 0.2 kJ/mol. This suggested a hydrophobic site or sites of action. The regularity of the change in free energy with chain length was maintained up to, and including, n-decanol. This implied that the site(s) could accommodate a ten-carbon chain as readily as an eight carbon chain. 4. The voltage dependencies of IA current activation and steady state inactivation were not consistently altered by treatment with n-alkanols at concentrations around or above their current suppression ED50 concentrations. 5. The kinetics of current activation and inactivation were affected, particularly by lower chain length compounds. At 60 mM n-butanol reduced the time constant for development of inactivation of open channels (tau b) by 56%, while 0.016 mM n decanol produced only a 13% reduction. n-Butanol (60 mM) also caused a substantial (76%) reduction in the time constant for development of inactivation in channels which were presumed to be closed. The effects of n-alkanols on the current time-to-peak (tc) were complex, showing both increases and decreases, but these actions also declined with chain length. Methyl hexanoate (1 mM) reduced tau b by around 30% and tc by around 20%. 6. n-Alkanols have now been shown to inhibit a number of voltage-gated ion conductances.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293278 TI - A developmentally regulated blood-cerebrospinal fluid transfer mechanism for albumin in immature rats. AB - 1. The transfer of albumin between the blood and the cerebrospinal fluid (CSF) has been investigated in neonatal (3 days old) and juvenile (20 days old) rats. At both stages of postnatal development, all of the albumin present in the CSF can be accounted for by transfer from the blood. Thus it is unlikely that in situ synthesis of albumin contributes to the naturally high levels of albumin in CSF in the developing brain. 2. The high concentration of albumin in CSF of the neonatal rat brain cannot be accounted for solely by diffusion from the blood. In the 3-day-old rat, only about one quarter of the albumin in CSF enters by diffusion from the blood, whilst the remainder appears to be transported into the CSF by a specific mechanism which can discriminate between different species of albumin. The specific transport component of albumin transfer between the blood and the CSF appears to be developmentally regulated and is not apparent in 20-day old rats. 3. Chemical modification of albumin resulting in either an increase or a decrease in electrophoretic mobility (at pH 7.4), significantly reduces blood CSF transfer of albumin in 3-day-old rats, but has little effect in the 20-day old rat. Thus overall molecular charge does not appear to be an important feature of the species-specific blood-CSF albumin transport mechanism in neonatal rats. PMID- 1293277 TI - Activation of N-methyl-D-aspartate receptors by L-glutamate in cells dissociated from adult rat hippocampus. AB - 1. Single channel recording techniques were used to study the ion channel openings resulting from activation of N-methyl-D-aspartate (NMDA) receptors by the agonist glutamate. Patches were from cells acutely dissociated from adult rat hippocampus (CA1). Channel activity was studied at low glutamate concentrations (20-100 nM) with 1 microM-glycine, in the absence of extracellular divalent cations. 2. Channel openings were to two main conductance levels corresponding to 50 pS and 40 pS openings in extracellular solution with 1 mM-Ca2+. Around 80% of openings were to the large conductance level. The single channel conductances increased as extracellular Ca2+ was reduced. 3. Distributions of channel open times were described by three exponential components of 87 microseconds, 0.91 ms and 4.72 ms (relative areas of 51, 31 and 18%). Most long openings were to the large conductance level. 4. The channel closed time distribution was complex, requiring five exponential components to describe it adequately. Of these five components, at least three, with time constants of 68 microseconds, 0.72 ms and 7.6 ms (relative areas of 38, 12 and 17%) represent gaps within single activations of the receptor. The presence of a component with a mean of 7.6 ms is notable because gaps of this length have not previously been identified as being within single NMDA receptor channel activations. 5. Channel activations were identified as including gaps underlying at least the first three closed time components. Activations consisted of clusters of channel openings. Distributions of the length of these clusters had mean time constants of 88 microseconds, 3.4 ms and 32 ms (relative areas of 45, 25 and 30%). Long clusters contained short, intermediate and long duration openings as well as subconductance openings. The open probability within clusters averaged 0.62. Three components were evident in distributions of the number of openings per cluster. These had mean values of 1.22, 3.2 and 11 openings per cluster. 6. An inverse correlation was evident between the length of adjacent open and closed times. When open intervals were separated into groups based on the length of adjacent gaps, the time constants of the exponential components in these conditional open time distributions were independent of the length of the adjacent gap. This supports the idea that the NMDA receptor channel gating has the properties of a discrete Markov process. 7. The long duration of NMDA receptor channel clusters suggests that they contribute to the slow time course of the NMDA receptor-mediated synaptic current. PMID- 1293279 TI - An analysis of the long-lasting after-hyperpolarization of guinea-pig vagal motoneurones. AB - 1. The long-lasting after-hyperpolarization which characterizes the neurones of the dorsal motor nucleus of the vagus in the guinea-pig was studied in vitro. 2. Following a train of action potentials, vagal motoneurones develop a long-lasting after-hyperpolarization. Two different shapes of long-lasting after hyperpolarization were encountered: an after-hyperpolarization which slowly (0.6 1.2 s) and monotonically developed to peak value; and a second type of long lasting after-hyperpolarization where the onset of the slow component appears to be masked by an early, relatively fast component. Both shapes of long-lasting after-hyperpolarization depend on Ca2+ influx and increase as a function of the number of action potentials in the train. 3. A novel procedure was used to analyse the ionic processes which underlie the long-lasting after hyperpolarization. The neuronal responses to a series of long (7 s) hyperpolarizing current pulses during the long-lasting after-hyperpolarization were recorded and the voltage-current curves at 600 different time points along the long-lasting after-hyperpolarization were plotted. The conductance and the reversal potential at each time point were calculated from the slope and the intersection of these curves, respectively. 4. Using this procedure it was found that the long-lasting after-hyperpolarization consists of two conductances that differ in kinetic properties and reversal potential: an early conductance which peaks shortly after the end of the train and decays in a few tenths of seconds (EAHP), and a late conductance which develops slowly (time to peak about 1 s) and decays in 3-8 s (LAHP). The reversal potential for the early conductance is 10 mV more positive than the reversal potential for the late conductance (-84 mV); the latter reversal potential is in agreement with the K+ equilibrium potential. The different shapes of long-lasting after-hyperpolarization can be explained by different ratios of these two conductances. 5. Noradrenaline (10 microM) selectively blocks the late conductance, without an observable effect on the Ca2+ action potential. 6. The behaviour of the noradrenaline-sensitive late conductance was analysed. The amplitude of the conductance change increased sigmoidally as a function of the number of spikes in the train. A log-log plot suggests that at least two Ca2+ ions participate in the opening of a K+ channel. 7. A model that accounts for the slow kinetics of the late conductance was constructed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293280 TI - The effects of hypoxia on the ventilatory response to sudden changes in CO2 in newborn piglets. AB - 1. The ventilatory response to square-wave challenges in end-tidal partial pressure of CO2 (PCO2) was investigated at three levels of arterial PO2 (Pa,O2) in nineteen anaesthetized 2- to 11-day-old piglets. 2. The ventilatory responses, measured on a breath-to-breath basis, were separated into a peripheral and a central component using a two-compartment model. Both components were described by a CO2 sensitivity, a time constant, a time delay and a single offset. 3. Fifty six responses were analysed against a background of normoxaemia (Pa,O2 = 12.70 +/ 0.72 kPa, mean +/- S.D.), fifty-three against a background of moderate hypoxaemia (Pa,O2 = 8.63 +/- 0.34 kPa) and fifty-one against a background of severe hypoxaemia (Pa,O2 = 4.98 +/- 0.30 kPa). 4. The sensitivity of the peripheral chemoreceptors in mediating the response to CO2 increased from 38.3 +/ 17.0 ml min-1 kPa-1 kg-1 during normoxaemia to 48.8 +/- 15.3 ml min-1 kPa-1 kg-1 during moderate hypoxaemia and to 72.9 +/- 24.0 ml min-1 kPa-1 kg-1 at severe hypoxaemia. 5. As compared with the central CO2 sensitivity during moderate hypoxaemia and normoxaemia (104.0 +/- 39.0 and 100.8 +/- 41.6 ml min-1 kPa-1 kg 1, respectively) it decreased to 85.9 +/- 54.1 ml min-1 kPa-1 kg-1 at severe hypoxaemia. 6. We conclude that in newborn piglets there is a positive interaction between hypoxia and hypercapnia at the level of the peripheral chemoreceptors while severe hypoxaemia reduced the CO2 sensitivity centrally. PMID- 1293281 TI - Corticospinal volleys evoked by electrical stimulation of human motor cortex after withdrawal of volatile anaesthetics. AB - 1. In twenty-two neurologically normal patients undergoing surgery for scoliosis, corticospinal volleys to transcranial electrical stimulation of the motor cortex were recorded from the spinal cord using epidural electrodes. While anaesthesia was maintained by nitrous oxide and narcotics, volatile anaesthetics were withdrawn to determine whether such agents had a depressant effect on the evoked corticospinal volley. 2. Profound changes were documented in liminal D waves, there being an increase in amplitude averaging 392% following withdrawal of the volatile anaesthetic. There was a proportionately smaller increase (averaging 26%) in supraliminal D waves; these had a complex bifid or trifid shape indicating that some corticofugal axons were being activated deep to cortex. In general the effect on the D wave of withdrawing the anaesthetic agent was similar to that of increasing stimulus intensity. 3. Withdrawal of isoflurane dramatically increased the number of I waves and their mean amplitude. In the absence of isoflurane, I3 (mean latency 3.5 ms after the D wave) became the dominant I wave. The amplitude of I2 (mean latency 2.2 ms) became slightly smaller. The change in I waves could not be likened to an increase in stimulus intensity, because I waves invariably increase in, or remain of the same, amplitude as stimulus intensity is increased. 4. These findings indicate that changes in motor cortex excitability can result in major changes in the corticospinal volley produced by transcranial electrical stimulation, affecting both the D wave and I waves. They caution against identifying a cortical action solely on the basis of a change in the responses to magnetic stimulation of motor cortex but no such change to electrical stimulation. PMID- 1293282 TI - Inhibitory synaptic currents in rat cerebellar Purkinje cells: modulation by postsynaptic depolarization. AB - 1. Synaptic currents were recorded in voltage-clamped cerebellar Purkinje cells using the tight-seal whole-cell recording technique. Cells were dialysed with a CsCl solution and were held at -60 or -70 mV. Inhibitory interneurones (basket and stellate cells) were stimulated using an extracellular pipette positioned in the molecular layer. Blockers of excitatory glutamatergic synapses were included in the bath solution. 2. Evoked synaptic currents were observed after a latency of 3-4 ms. The time course of synaptic currents could in most cases be fitted to a biexponential curve, with a rise time constant, tau on, of 1-3 ms and a decay time constant, tau off, of 7-13 ms. These currents were blocked by bicuculline. 3. The mean amplitude of evoked synaptic currents increased in discrete steps when the voltage applied to the stimulating pipette was increased. At each level, very prominent fluctuations of the amplitude were observed among trials. 4. Complex synaptic currents corresponding to repetitive activity of the presynaptic interneurone were occasionally observed, particularly with high intensity presynaptic stimulation. This repetitive activity could lead to bursts of synaptic currents lasting for several seconds. 5. Following a depolarizing voltage train in the postsynaptic Purkinje cell, the amplitude of evoked synaptic currents was first inhibited, and then potentiated. The inhibition was accompanied by a small but consistent increase in tau off and by no alteration in tau on. When using small intensity presynaptic stimuli, it was found that the probability of failures was greatly enhanced. The inhibitory phase lasted for about 1 min before giving way to potentiation. The potentiation returned to the control with a time to half-decay of 12.9 +/- 0.9 min. 6. The present results give further evidence to a previously proposed hypothesis that the inhibition produced by Purkinje cell depolarization is mainly presynaptic. The longer lasting potentiation, on the other hand, has most probably a postsynaptic origin. Cerebellar Purkinje cells receive inhibitory GABAergic inputs from two classes of interneurones located in the molecular layer (reviewed in Palay & Chan-Palay, 1974; Ito, 1984). Basket cells are closest to the Purkinje cell layer and address their inhibitory signal primarily to the soma and to the main dendrites. Stellate cells are more externally located and have contacts with the more distal part of the dendritic arborization of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293283 TI - Ionic mechanisms mediating 5-hydroxytryptamine- and noradrenaline-evoked depolarization of adult rat facial motoneurones. AB - 1. The actions of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) on the membrane properties of facial motoneurones in slices from the adult rat brainstem in vitro were examined using intracellular recording techniques. 2. In voltage clamp recording, hyperpolarizing voltage steps (> 20 mV), from holding potentials at or close to the resting potential, induced a slowly activating, voltage dependent inward current possessing properties similar to the hyperpolarization activated current (Ih) seen in other cell types. From tail current analysis two groups of facial motoneurones can be distinguished in terms of the activation range for Ih, one with a half-maximal activation at -81 mV and the other at -94 mV but with similar shapes. 3. 5-HT (120/126) and NA (21/21) depolarized facial motoneurones. The reversal potentials (Em) obtained from peak voltage amplitude I V plots in varying extracellular potassium concentrations suggested mechanisms involving a decrease in K+ conductance. 4. Under voltage clamp, close to the resting potential, both 5-HT (39/41) and NA (13/13) evoked inward currents. 5. I V plots and plots of 5-HT-sensitive current at different membrane potentials, obtained from currents evoked by voltage steps and measured before the development of Ih (instantaneous current), indicated that the 5-HT-evoked inward current was predominately associated with a decrease in conductance but with a range of reversal potentials for 5-HT (E5-HT) from close to, to much more negative than the reversal potential for a potassium conductance (EK). In some cases no change or increases in instantaneous conductance were observed. 6. Steady-state I-V relationships and plots of 5-HT-sensitive current, measured after development of Ih, indicated a 5-HT-associated conductance increase with a time and voltage dependence close to that of Ih, which could be abolished by extracellular caesium (2-5 mM). 7. The NA-evoked inward current was always associated with a decrease in conductance. Instantaneous and steady-state I-V relationships as well as plots of NA-sensitive current indicated a reversal potential at EK. 8. The activation curve for Ih was shifted to more positive potentials in the presence of 5-HT. The time constant for activation of Ih showed a similar shift. 9. 5-Carboxamidotryptamine (5-CT), a 5-HT receptor agonist, was selective for the enhancement of Ih and only evoked an inward current when the holding potential was within the activation range of Ih.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293284 TI - A contraction-related component of slow inward current in dog ventricular muscle and its relation to Na(+)-Ca2+ exchange. AB - 1. The slow inward current component related to contraction (Isic) was studied in voltage clamp experiments on canine ventricular trabeculae at 30 degrees C with the aims of (a) estimating its relation to electrogenic Na(+)-Ca2+ exchange and (b) comparing it with similar currents as reported in cardiac myocytes. 2. Isic may be recorded under conditions of augmented contractility in response to depolarizing pulses below the threshold of the classic slow inward current (presumably mediated by L-type Ca2+ channels). In responses to identical depolarizing clamp pulses the peak value of Isic is directly related to the amplitude of contraction (Fmax). Isic peaks about 60 ms after the onset of depolarization and declines with a half-time of about 110 ms. 3. The voltage threshold of Isic activation is the same as the threshold of contraction. The positive inotropic clamp preconditions shift both thresholds to more negative values of membrane voltage, i.e. below the threshold of the classic slow inward current. 4. Isic may also be recorded as a slowly decaying inwardly directed current 'tail' after depolarizing pulses. In this representation the peak value of Isic changes with duration of the depolarizing pulses, again in parallel with Fmax. In response to pulses shorter than 100 ms both variables increase with depolarization time. If initial conditions remain constant, further prolongation of the pulse does not significantly influence either one (tail currents follow a common envelope). 5. Isic differs from classic slow inward current by: (a) its direct relation to contraction, (b) the slower decay of the current tail on repolarization, (c) slower restitution corresponding to the mechanical restitution, (d) its relative insensitivity to Ca(2+)-blocking agents (the decrease of Isic is secondary to the negative inotropic of Ca(2+)-blocking agents (the decrease of Isic is secondary to the negative inotropic effect) and (e) its disappearance after Sr2+ substitution for Ca2+. 6. The manifestations of Isic in multicellular preparations do not differ significantly from those reported in isolated myocytes (in contrast to calcium current). 7. The analysis of the correlation between Isic and Fmax transients during trains of identical test depolarizing pulses at variable extra- and intracellular ionic concentrations (changes of [Ca2+]o, 50% Li+ substitution for Na+, strophanthidin) indicate that the observed effects conform to the predictions based on a quantitative model of Na(+)-Ca2+ exchange. 8. It is concluded that Isic is activated by a transient increase of [Ca2+]i, in consequence of the release from the reticular stores.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293285 TI - Endothelium-derived vasodilator responses to sympathetic stimulation of the submandibular gland in the cat. AB - 1. The extent to which vasodilator responses to electrical stimulation of the sympathetic innervation, in the submandibular gland of the cat, depend upon release of endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anaesthetized cats given N-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine. 2. Close intra arterial infusions of L-NAME (> or = 100 mg kg-1) produced a steady and significant rise in mean aortic pressure together with a steady increase in basal submandibular vascular resistance over the next 20-30 min. It also reduced, but failed to abolish, the vasodilatation which occurs during intermittent stimulation of the sympathetic innervation (20 Hz for 1 s at 10 s intervals) together with the after-dilatation which occurs immediately after a period of continuous stimulation of these nerve fibres (2 Hz). 3. In cats pretreated with the beta-blocker propranolol (> or = 1.0 mg kg-1) both vasodilator responses were reduced, but persisted until L-NAME was administered, whereupon both were abolished. 4. It is concluded that release of EDRF within the submandibular gland of the cat contributes to the basal tone of the vasculature and is responsible for the alpha-adrenergic vasodilator responses to stimulation of the sympathetic innervation, but not for the beta-adrenergic vasodilator responses. PMID- 1293286 TI - A Cl- conductance sensitive to external pH in the apical membrane of rat duodenal enterocytes. AB - 1. The pH dependence of a chloride conductance in the apical membrane of rat duodenal enterocytes was examined. 2. A stepwise reduction of both internal and external pH from 7.4 to 6.8 resulted in a significant stimulation of 36Cl flux driven by an inside-positive membrane potential. 3. A stepwise reduction in pH had no significant effect upon other parameters such as the initial rate of D [3H]glucose or voltage-independent 36Cl uptake, suggesting a specific effect upon the chloride conductance. 4. The pH-dependent stimulation of 36Cl uptake exhibited saturation kinetics, with an apparent Vmax (maximum velocity) of 5.5 nmol (mg protein)-1 (4 s)-1 and an apparent Km (Michaelis-Menten constant) of 88 nM H+ ions. 5. To determine the site of action of protons upon the conductance the effect of asymmetrically reducing either the internal or external pH was examined. 6. A step reduction of extracellular pH from 7.8 to 6.8 significantly stimulated the rate of 36Cl uptake. In contrast, a step reduction of internal pH from 7.8 to 6.8 was without effect upon the rate of 36Cl uptake. 7. These results suggest that the chloride conductance on the apical membrane of rat duodenal enterocytes is allosterically regulated by protons at an external site. PMID- 1293287 TI - Effects of left atrial receptor stimulation on carotid chemoreceptor-induced renal responses in dogs. AB - 1. Dogs were anaesthetized with thiopentone sodium and alpha-chloralose and artificially ventilated. The carotid sinus regions were vascularly isolated and perfused with arterial or venous blood to stimulate the chemoreceptors. Left atrial receptors were stimulated by distending four balloons, three in the left pulmonary vein-atrial junctions and one in the left atrial appendage. Mean aortic pressure was held constant by means of a pressure control device. Atenolol and atropine (2.0 and 0.5 mg kg-1, respectively), and gallamine triethiodide (3.0 mg kg-1 h-1) were given I.V. Renal blood flow was measured by an electromagnetic flowmeter, glomerular filtration rate by creatinine clearance, urinary sodium by flame photometry and solute excretion by osmometry. 2. In fifteen tests in eight dogs (in one dog responses of both left and right kidneys were determined), at a constant aortic pressure (AoP) of 92.0 +/- 3.2 mmHg, and carotid sinus pressure (CSP) of 95.0 +/- 2.0 mmHg, stimulation of left atrial receptors with balloon inflation resulted in significant increases in renal blood flow (RBF) by 8.3 +/- 0.9 from 255.0 +/- 14.6 ml min-1 (100 g kidney weight)-1 (n = 9), in glomerular filtration rate (GFR) by 4.1 +/- 0.6 from 21.2 +/- 1.9 ml min-1 (100 g)-1, in filtration fraction (FF) by 0.04 +/- 0.003 from 0.20 +/- 0.01, in urine flow rate (V) by 0.08 +/- 0.02 from 0.33 +/- 0.05 ml min-1 (100 g)-1, in sodium excretion (UNaV) by 4.4 +/- 0.9 from 27.7 +/- 4.2 mumol min-1 (100 g)-1, in osmolar excretion (UosmV) by 62.0 +/- 5.6 from 303.0 +/- 28.3 mu osmol min-1 (100 g)-1, and in a decrease in free water clearance (CH2O) by 0.13 +/- 0.03 from -0.63 +/- 0.04 ml min-1 (100 g)-1. Left atrial pressure (LAP) and heart rate (HR) did not change significantly from 6.9 +/- 0.3 cmH2O, and 133.0 +/- 3.4 beats min-1 respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293288 TI - Multiple motor pathways to single smooth muscle cells in the ferret trachea. AB - 1. We investigated the distribution and characteristics of motor pathways to individual smooth muscle cells activated by electrical stimulation of either, single nerves which enter the tracheal plexus (inlet nerves), or a longitudinal nerve trunk (LNT) located near the entrance of an inlet nerve into the plexus. Excitatory junction potentials (EJPs) were recorded using intracellular microelectrodes as an index of smooth muscle cell activation. In all experiments EJPs were completely blocked by tetrodotoxin and by atropine. 2. In smooth muscle fields located in the caudal direction from the point of inlet or LNT nerve stimulation, neural input decreased as a function of distance. There was evidence of a demarcated area innervated by neurons entering the plexus in one inlet nerve. In smooth muscle fields located in the rostral or transverse direction from the site of nerve stimulation, no such demarcated area could be identified. 3. Of the smooth muscle cells located within the innervated fields studied, 83 95% were activated following stimulation of a single inlet nerve or LNT. Evoked EJPs were similar in different innervated cells or units of electrically coupled cells located within the same 1 mm2 'field'. 4. There was overlapping cholinergic motor input to single smooth muscle cells originating from neurons present in different inlet nerves or different neurons present in the same inlet nerve or region of the LNT. Multiple small step increases in the voltage used to stimulate a LNT resulted in three or four step increases in EJP amplitudes. This gives a minimal value for the number of motor pathways that can be activated by neurons in a region of LNT leading to a single smooth muscle cell. 5. Motor pathways to smooth muscle cells located in caudal and rostral fields ran initially in the LNT and exited in proximity to the smooth muscle cell studied. 6. Motor pathways used in transmitting signals to smooth muscle cells to different areas of trachealis muscle varied in their sensitivity to hexamethonium or curare. EJPs evoked in fields located in the caudal direction from the stimulating electrode were abolished by these drugs. Muscle cells located in different rostral fields showed EJPs that were either sensitive or resistant to these drugs. 7. The rostral hexamethonium-resistant pathway ran initially in the LNT but it exited from the LNT several millimetres before reaching the level of the smooth muscle field innervated. This pathway followed stimulation frequencies up to 25 Hz. The final neuron in this pathway released acetylcholine and evoked EJPs were entirely inhibited by atropine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293289 TI - The classification of afferents from muscle spindles of the jaw-closing muscles of the cat. AB - 1. The effects of the muscle-depolarizing drug succinylcholine (SCh) on the stretch responses of jaw-closer muscle spindle afferents were studied in the anaesthetized cat. Using ramp and hold stretches repeated every 6 s the basic measurements made were: initial frequency (IF), peak frequency (PF) and static index (SI), the frequency 0.5 s after the end of the ramp of stretch. Derived from these were: dynamic difference (DD) = PF-IF, dynamic index (DI) = PF-SI and static difference (SD) = SI-IF. Increases in these measures caused by a single I.V. dose of SCh (200 micrograms kg-1) are symbolized by the prefix delta. 2. In a population of 234 units, delta DD and delta IF were each distributed bimodally, but were uncorrelated, thus defining four subgroups. 3. delta DD was argued to be an index of the effect of bag1 intrafusal fibre contraction and delta IF to be an index of the effect of bag2 fibre contraction. On this basis it is proposed that units can be divided into four groups according to the predominant influences of the bag1, bag2 and chain fibres as b1c (6.8%), b1b2c (22.2%), b2c (54.3%) or c (16.7%). 4. Testing with sine wave stretches at 1 Hz showed that changes in mean frequency and amplitude of response caused by SCh correlated with delta IF and delta DD respectively, but separated groups of units much less effectively than did ramp and hold testing. 5. Evidence is presented to indicate that the control value of DD in passive spindles does not relate to the potential strength of bag1 fibre effects in fully activated spindles. The bag1 fibre appears to contribute little to responses of spindle afferents in the passive state. DD is superior to DI as a measure of bag1 effects. 6. Conduction velocity was unimodally distributed in masseter spindle afferents and was not correlated with delta DD or delta IF and was therefore of no value in classifying them. 7. Neither the threshold of afferents to quick transient stretch nor the coefficient of variation of interspike intervals provided any significant additional help in classification. 8. The unexpectedly high proportion of units of b2c type is thought to include primaries lacking appreciable bag1 fibre contacts and secondaries with more or less substantial bag2 contracts. PMID- 1293290 TI - The effect of succinylcholine on cat gastrocnemius muscle spindle afferents of different types. AB - 1. A population of 269 gastrocnemius muscle spindle afferents have been studied in anaesthetized cats for the effects of succinylcholine (SCh) on their response to ramp and hold stretches repeated every 6 s. The effectiveness and reliability of the SCh test was improved by prior stimulation of the muscle at 10 Hz for 30 s to increase the blood flow. 2. Responses have been assessed from averaged cycle histograms before and after a single I.V. dose of SCh of 200 micrograms kg-1. As for previous studies of jaw muscle spindles the basic measurements were initial frequency (IF), peak frequency (PF) and static index (SI), the frequency 0.5 s after the end of the ramp of stretch. Dynamic difference (DD = PF-IF), dynamic index (DI = PF-SI) and static difference (SD = SI-IF) were derived from these and increases caused by SCh indicated by the prefix delta. 3. delta DD and delta IF were each distributed bimodally and since they were uncorrelated formed the basis for a four-way classification. Since delta DD can be attributed to activation of bag1 (b1) intrafusal fibres and delta IF to bag2 (b2) fibres, while all afferents receive input from chain (c) fibres it is proposed as with the jaw spindles that the classes correspond to predominant influence from b1c, b1b2c, b2c and c intrafusal fibres. 4. The proportion of units in the different groups were similar to those in the jaw muscles except for there being very few b1c type in gastrocnemius. 5. Conduction velocity was bimodally distributed with the best dividing line at 63.2 m s-1. The b1b2c units were all, save one, in the fast group, while the b2c units were equally divided between fast and slow. 6. Mean control values for DD did not differ between the b1b2c and the b2c groups, which is taken to indicate that the b1 fibre does not contribute significantly to the dynamic stretch response of spindles with no intrafusal contraction. 7. The results emphasize the importance of recognizing that some apparently primary afferents lack b1 fibre influence, while many secondaries have marked b2 fibre influence. 8. The importance of the SCh classification is discussed in relation to the identification of fusimotor effects on spindle discharge and in relation to studies of central connectivity. PMID- 1293292 TI - Role of basal release of nitric oxide on coronary flow and mechanical performance of the isolated rat heart. AB - 1. The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function was studied in isolated working rat hearts. 2. The inhibition of basal release of NO by L-Ng-monomethylarginine (L-NMMA; 500 microM), a specific inhibitor of its synthesis, induced a reduction of coronary flow to 39.1% (+/- 3.4) of its basal level. 3. Associated with this was a drop of cardiac output to 58.10% (+/- 5.42) of control values. 4. This mechanical dysfunction, which was more pronounced in hypertrophied hearts, appears to be related to ischaemia, as it was prevented by simultaneously administered glyceryl trinitrate. Furthermore, L-NMMA did not alter the contractile activity of isolated cardiac myocytes, thereby excluding a direct toxic effect. 5. These findings provide evidence that NO plays a crucial role in the maintenance of basal coronary flow and appears to be essential for sustaining mechanical activity. PMID- 1293291 TI - Ventilatory response to hyperoxia in newborn rats born in hypoxia--possible relationship to carotid body dopamine. AB - 1. The influence of postnatal hypoxia on regulation of breathing and turnover rate of carotid body dopamine was examined in newborn rats. The percentage change in frequency, tidal volume and ventilation elicited by transient hyperoxia was assessed by flow plethysmography in unanaesthetized pups. The alteration in ventilation was taken as an index of peripheral chemoreceptor activity. 2. The rats were born and reared in hypoxia. The inspired oxygen fraction (FI,O2) was 0.12-0.14 until 2 days after delivery when the rats were placed into room air and the ventilatory chemoreflex was tested. At 4 days of age, i.e. 2 days after termination of hypoxia, the rats were tested again. The ventilatory data were compared with those from a previous study in normoxic rats. 3. We found a smaller decrease in ventilation (8.8 +/- 3.9%, mean +/- S.D.) in the hypoxic rats at 2 days of age compared with normoxic rats (22.7 +/- 6.4%; P < 0.001). In contrast, at 4 days of age there was no difference in ventilatory response between the posthypoxic rats (19.2 +/- 4.6%) and normoxic pups (18.6 +/- 4.9%). 4. The turnover rates of dopamine in carotid bodies were determined at 0-6, 6-12, 12-24 h and 2 days after birth in hypoxic rats and in 2-day-old posthypoxic rat pups at different time intervals after termination of hypoxia. Postnatal hypoxia sustained a high turnover rate which decreased after termination of the hypoxia. 5. We propose that the weak chemoreflex in hypoxic rat pups is brought about by a high release of carotid body dopamine. PMID- 1293293 TI - The ventilatory response to CO2 of the peripheral and central chemoreflex loop before and after sustained hypoxia in man. AB - 1. The ventilatory response to sustained hypoxia is characterized by a fast increase due to the peripheral chemoreceptors followed by a slow decline. The mechanism of this decline is unknown. 2. To investigate the characteristics of the ventilatory response to sustained hypoxia ten healthy subjects were exposed to two consecutive periods of isocapnic hypoxia (arterial saturation 78%) separated by a 5 min exposure to isocapnic normoxia. 3. The acute hypoxic response to the second exposure to hypoxia (mean increase in ventilation +/- S.E.M., 7.2 +/- 0.8 l min-1) was significantly depressed (P = 0.04) compared to the first one (9.5 +/- 1.3 l min-1). 4. To investigate whether this depression was due to central or peripheral effects or both we measured, in the same ten subjects, the normoxic ventilatory response to CO2 before and after a period of 25 min of hypoxia using the technique of dynamic end-tidal forcing. 5. Each response was separated into a fast peripheral and slow central component characterized by a CO2 sensitivity, time constant, time delay and an off-set. 6. A total of thirty-six prehypoxic and thirty posthypoxic responses were analysed. The ventilatory CO2 sensitivities of the peripheral and central chemoreflex loops and the overall off-set (apnoeic threshold) after 25 min of hypoxia were somewhat larger than their prehypoxic values, but this effect was not significant. 7. We argue that the hypoxic ventilatory decline in man is due to a change in the off set of the peripheral chemoreflex loop. PMID- 1293294 TI - [Electromechanical transductions and a new substance responsible for functioning of input mechanism for E-C coupling]. PMID- 1293295 TI - Phonological transformations in conduction aphasia. AB - Different explanations and subtypes of conduction aphasia are analyzed. Characteristics of literal paraphasias in parietal-insular conduction aphasia are discussed, emphasizing that paraphasias in conduction aphasia are articulatory based (articulatory literal paraphasias) and due mainly to phoneme substitutions and phoneme deletions; they result basically in switches in phoneme manner and place of articulation. Similarities between errors in ideomotor apraxia and conduction aphasia language deficits are presented. It is proposed that language deviations (in oral as in written language) in conduction aphasia can be understood as a segmentary apraxia of speech. PMID- 1293296 TI - Cytogenetic adaptive response of cultured fish cells to low doses of X-rays. AB - The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. PMID- 1293297 TI - Gamma-radiation produces abnormal Bergmann fibers and ectopic granule cells in mouse cerebellar cortex. AB - Morphological changes in Bergmann glial fibers in the developing cerebellar cortex produced by exposure to gamma-rays were investigated in association with ectopic granule cells. Six-day-old mice that had been exposed to 3 Gy of gamma radiation were killed 6 hours after exposure or at 7 through 30 days of age. Their cerebella were examined histologically and immunohistochemically for glial fibrillary acidic protein in Bergmann fibers. Extensive cell death took place in the external granular layer (EGL) of the cerebellum from 6 through 24 hours after exposure. This led to the thinning of the EGL and a decrease in the number of migrating cells in the molecular layer. The number of Bergmann cells was not decreased, but the fibers in the molecular layer were distorted; whereas, in the control these fibers were straight and perpendicular to the pial surface. The EGL began to recover 2 days after exposure, and abnormally oriented migrating cells were seen. At 17 days of age, some cell clustering was observed in the molecular layer of the irradiated cerebellum. Distortion of the Bergmann fibers was marked in regions where ectopic granule cells appeared at 30 days of age. These findings suggest that the distortion of Bergmann fibers leads to the production of ectopic granule cells after exposure to gamma-radiation. PMID- 1293298 TI - Modification of radiosensitivity by the so-called tissue recovery stimulator. I. Radiosensitizing effects of solcoseryl. AB - The effect of solcoseryl on the growth, radiosensitization and ability of V79 cells to recover from X-ray-induced damage has been observed. Solcoseryl at 0.8 mg/ml was the optimal concentration for the stimulation of cell growth. Increased sensitivity to X-irradiation was found in the shoulder region of V79 cells treated before and after irradiation with solcoseryl (0.8 mg/ml). The Dq and extrapolation number (n) decreased. Solcoseryl treatment apparently does not reduce split dose recovery or inhibit the repair of potentially lethal damage. Flow cytofluorometry studies of the cell cycle distribution and mitotic index show that solcoseryl inhibits the expression of radiation-induced cell arrest in the G2 phase of the cell cycle. Although this action increases radiation sensitization, additional mechanisms probably exist. PMID- 1293299 TI - The effect of OK-432 upon erythropoietic recovery in sub-lethally irradiated mice: a preliminary report. AB - OK-432, a multicytokine inducer and clinically used as an immunopotentiating anti cancer agent, is known to induce IL-1 and TNF-alpha. The suppressive effect of IL 1 and TNF-alpha on erythropoiesis could limit the clinical use of OK-432 in cancer treatment, especially when combined with radiotherapy. In this study, the effect of OK-432 on normal and X-ray impaired erythropoiesis was examined. C57BL/6J mice were injected with a single dose of OK-432 (5.0 KE). Erythropoietic activity was measured by 59Fe incorporation into circulating erythrocytes and the heme iron fraction of erythropoietic tissue. When irradiated with 662 cGy of X rays, OK-432 prolonged the survival of mice. No significant change in erythropoiesis was observed when normal mice were treated with OK-432. When treated with OK-432, the recovery of erythropoiesis after irradiation was promoted as judged by the uptake of 59Fe into erythrocytes. This promotion was observed when OK-432 was injected within 1 day before or within 3 hours after the irradiation with 284 cGy of X-rays. This promoting effect, however, appeared to be limited to the spleen. Whether the combination of OK-432 with radiotherapy has the potential to improve the treatment of malignant tumors is still a subject of controversy. The present results, nevertheless, suggest that when combined with radiotherapy, OK-432, at the very least, may have no adverse effects on erythropoiesis. PMID- 1293300 TI - Transfer of plutonium to rat embryos in vivo and in vitro. AB - The 239Pu distribution in the 12.5-day-old rat conceptus was compared between in vivo and in vitro experimental systems to establish a possible mechanism of cross placental transfer of this radionuclide. In the in vivo study, plutonium citrate solution was injected intravenously to pregnant Wistar rats. In the in vitro study, either plutonium citrate or plutonium hydroxide colloid was administered, as a solution of Eagle MEM and FCS containing 239Pu at the concentration used in the maternal serum in the in vivo experiments, to rat conceptuses maintained by the whole-embryo culture method. The concentration of 239Pu in the yolk sac (239Pu activity per gram wet weight) were much higher than in the embryo in both the in vivo and in vitro experiments, suggesting that the yolk sac may be an effective barrier against the transfer of plutonium to the embryos. The ratios of the 239Pu concentration in the yolk sac to that in the embryo were relatively constant with time after administration in the in vitro system; 18-27 for plutonium citrate and 67-84 for plutonium hydroxide. In the in vivo experiment, these ratios changed with time after injection; 15 at 5 min and 62 and 60 min after injection. This suggests that in the in vivo system, the chemical form of 239Pu changed with time after injection, probably to a macromolecular form such as the hydroxide colloid or plutonium-protein complex although 239Pu was injected to the maternal blood as citrate. PMID- 1293301 TI - Incorporation and distribution of tritium in rats exposed to tritiated rice or tritiated soybean. AB - The incorporation and distribution of tritium were examined in rats exposed to tritiated rice or tritiated soybean by single ingestion or continuous feeding. Results were compared with those for tritiated wheat and tritiated water in a previous study done under the same experimental conditions. All the tritiated crops examined were more efficiently incorporated into rat tissues than was tritiated water, the extent of incorporation depending on the kind of crop. The differences in incorporation were clear in organically bound tritium determined as tritium in dried tissue. The respective concentrations of organically bound tritium after a single ingestion of tritiated rice, tritiated wheat or tritiated soybean were about 10-20, 20-30 and 25-60 times higher than after the ingestion of tritiated water. After continuous feeding for 22 days with tritiated rice, tritiated wheat or tritiated soybean, the respective concentrations of organically bound tritium were 5-8, 6-11 and 10-25 times the values after continuous ingestion of tritiated water. At the end of continuous ingestion, the radiation dose rates to almost of the tissues from all three tritiated crops were estimated to be 2-3 times that for tritiated water. PMID- 1293302 TI - Carcinogenic effect of in utero 252Cf and 60Co irradiation in C57BL/6N x C3H/He F1 (B6C3F1) mice. AB - C57BL/6N x C3H/He F1 mice were exposed in utero to 0, 1.0 and 2.7 Gy of 252Cf or 60Co at day 16.5th of gestation. Mice of both sexes were observed for 2 years. The females in the irradiated groups showed increases in the incidences of pituitary, mammary gland, liver and lung tumors. 252Cf was more effective in inducing tumors than was 60Co. Interestingly, the incidence of hematopoietic tumors decreased by irradiations with 252Cf but not with 60Co. The incidences of liver tumors in males increased by 252Cf-irradiation, whereas, the incidences of skin and soft tissue tumors increased by 60Co-irradiation. These results indicate that irradiation in utero during the late embryonic stage can induce tumors postnatally after a long latency. Moreover, females irradiated in utero had disfunction of the ovaries, evidence of impairment of the female's specific hormonal environment. This may be the cause of the low incidence of ovarian tumors and the high incidences of liver, lung and pituitary tumors in these female mice. Females with pituitary tumors had a high serum prolactin, which might be responsible for the concurrence of mammary gland tumors. These results indicate the importance of host factors in the development of radiation-induced tumors. PMID- 1293303 TI - Heterogeneity of the radiosensitivity and origins of tissue macrophage colony forming cells. AB - Previous studies suggest that the radiosensitivity and origin of tissue macrophage precursors differ from those of hemopoietic macrophage colony-forming units (CFU-Ms) committed to macrophage-lineage cells. We assessed the origins of tissue macrophage colony-forming cells (M-CFCs) in mice by comparing their kinetics and radiosensitivities in the normal steady state and under the conditions of bone marrow depletion by 89Sr-administration and/or splenectomy. The results indicate that the radiosensitive peritoneal M-CFCs elicited by thioglycollate are derived from bone marrow macrophage precursors; where as alveolar M-CFCs, which are radioresistant, are self-sustained locally and independent of hemopoietic macrophage precursors. In contrast, highly radiosensitive liver M-CFCs are probably derived from CFU-Ms that appear to be propagated in the spleen in association with hemopoietic responses. PMID- 1293304 TI - Protective effects of various calcium antagonists against experimental arteriosclerosis. AB - Arterial walls altered by sclerotic processes accumulate lipids (particularly cholesterol) and calcium. Whereas the accumulation of lipids has long been incriminated as the major pathogenic factor involved in arteriosclerosis, concomitant arterial calcium overload has been considered of secondary importance. Using various animal models and specific calcium antagonists as experimental tools, we have shown the crucial role of excessive calcium uptake into arterial walls in the pathogenesis of arteriosclerotic lesions. Anticalcinotic vasoprotection with calcium antagonists has been demonstrated using light and electron microscopy, radiocalcium uptake experiments and calcium analyses with atomic absorption spectroscopy. The new 1,4-dihydropyridine calcium antagonist amlodipine has been shown to inhibit calcium accumulation in the internal elastic membrane of abdominal arteries of NaCl-loaded salt-sensitive Dahl-S rats, and consequently also exerts protective effects against arteriosclerotic lesions, shown particularly in the distal mesenteric artery branches. Formation of human coronary plaques is marked by a substantial local uptake of calcium, whereas there is a large overlap in the mural cholesterol content of healthy coronary arteries and plaques. Experimental findings in animals and with human tissue indicate that calcium antagonists such as amlodipine may provide a new approach to the prophylaxis of coronary artery lesions. PMID- 1293305 TI - Comparison of the effects of amlodipine and captopril on clinic and ambulatory blood pressure. AB - Forty-one patients with mild to moderate essential hypertension (sitting diastolic blood pressure (DBP) 95-114 mmHg) were randomised in a double-blind fashion to treatment with either amlodipine 5-10 mg once daily (n = 21) or captopril 25-50 mg twice daily (n = 20) over a period of 8 weeks. Office BP, heart rate and side effects were assessed during the run-in period on placebo, and after 2, 4 and 8 weeks' treatment. Blood pressure and heart rate were measured at the same time at each visit, 12 hours after the last captopril dose and 24 hours after the last amlodipine dose. At the end of the 8 week study, the reduction in sitting DBP was significantly greater (P = 0.002) with amlodipine. Ambulatory BP recordings were performed over a 24-hour period, at baseline and at the end of the study. Both treatment regimes significantly reduced clinic BP without affecting heart rate. However, amlodipine reduced ambulatory systolic (SBP) and DBP almost every hour over the whole circadian cycle, whereas the antihypertensive effect of captopril was attenuated during the final 3 hours of each dosing interval. The incidence of headache and peripheral oedema was identical between the two regimens. Only one patient taking amlodipine withdrew due to ankle swelling. This study demonstrates that the once-daily administration of amlodipine has a more sustained antihypertensive effect than does captopril taken twice daily. PMID- 1293306 TI - Circadian rhythms in cardiovascular disease: the crucial hours. AB - Major cardiovascular events, i.e. myocardial infarction and sudden death, have a circadian variation with a peak incidence during the morning hours. The factors possibly triggering those events, namely myocardial ischaemia, sympathetic tone and blood coagulability, have a similar circadian variation which could explain the circadian distribution of the major cardiovascular events. PMID- 1293307 TI - Intra-arterial monitoring of the antihypertensive effects of once-daily amlodipine. AB - Amlodipine is a dihydropyridine calcium antagonist with a long elimination half life making it suitable for once-daily dosing. This study used sphygmomanometric and intra-arterial ambulatory blood pressure (BP) monitoring to confirm the antihypertensive effect of a once-daily dose of amlodipine over the dosing interval. After a 2-week single-blind placebo run in, amlodipine was administered to 11 patients at a starting dose of 5 mg daily for 2 weeks increasing to 10 mg daily for a further 4 weeks if diastolic blood pressure (DBP) measured sphygmomanometrically was not < 90 mmHg or decreased by > 10 mmHg from baseline values. Intra-arterial blood pressure recordings for 24-hour periods were made at the end of the placebo run in and on completion of the active treatment phase. The effects of isometric and dynamic exercise and head-up tilting (60 degrees) on BP and heart rate were measured during ambulatory monitoring. Mean supine cuff BP was 169/104 mmHg (n = 11) at the end of the placebo treatment period and was reduced to 153/95 mmHg (n = 11) after 2 weeks of amlodipine treatment and 146/92 mmHg (n = 11) after 6 weeks of amlodipine treatment. There was no significant change in heart rate. Intra-arterial ambulatory monitoring showed that BP was controlled for the whole dosing interval with once-daily doses of amlodipine. The normal circadian pattern of BP changes was not altered. BP was reduced by amlodipine during exercise and physiological tests, but there was no postural hypotension and the BP and heart rate responses to exercise were not blunted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293308 TI - Pharmacokinetics of propetamphos following intravenous administration in the F344 rat. AB - Propetamphos [(E)-1-methylethyl 3-[[(ethylamino)methoxyphosphinothioyl]oxy]-2 butenoate], the active ingredient in Safrotin, is an organophosphate developed by Sandoz, Ltd. (Switzerland) as an insecticide (1). Although metabolism of propetamphos has been previously investigated (2,3), there is no pharmacokinetic data available in the literature. The current studies were undertaken to investigate the pharmacokinetics of propetamphos following intravenous administration in male and female Fischer 344 (F344) rats. Rats were dosed via an indwelling jugular cannula at a dose of 12 mg/kg (one-tenth the oral LD-50). Blood samples were withdrawn via the cannula at predetermined timepoints to quantitate plasma concentrations of propetamphos over time. Propetamphos is highly bound to plasma proteins (free fraction = 0.06). Free propetamphos concentration in plasma vs. time data were analyzed by noncompartmental methods. The terminal elimination rate constant, lambda, was significantly different for males versus females (0.015 min-1 for males and 0.037 min-1 for females, p = 0.001). Plasma was cleared of unbound propetamphos at rates of 0.559 +/- 0.069 and 0.828 +/- 0.181 L/min/kg for males and females (mean +/- standard error). Mean residence times (MRTs) for propetamphos in the body for males and females were 28.3 +/- 5.7 and 14.4 +/- 3.5 min, and the volume of distribution at steady state (Vss) was 14.7 +/- 2.6 and 12.3 +/- 4.5 L/kg. The differences in these parameters, clearance (CI), MRT, and Vss, were not statistically significant at the p < 0.05 level for males versus females, but MRT was nearly significantly different (p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293310 TI - Strand scission in DNA by gossypol and Cu(II): role of Cu(I) and oxygen-free radicals. AB - Gossypol, a polyphenolic binaphthyl dialdehyde found in cotton seeds, is a dietary mutagen and a potential male contraceptive. In the presence of Cu(II), gossypol caused breakage of supercoiled plasmid pBR322 DNA. The products were relaxed circles or a mixture of these and linear molecules. Other metal ions tested [Ni(II), Co(II), Mn(II), and Fe(II)] were ineffective or less effective in the DNA breakage reaction. In the case of gossypol-Cu(II) mediated cleavage, Cu(I) was shown to be an essential intermediate by using the Cu(I) sequestering reagent bathocuproine. By using job plots, it was established that in the absence of DNA, eight Cu(II) ions can be reduced by one gossypol molecule. The involvement of active oxygen species, such as singlet oxygen and H2O2, was established by the inhibition of DNA breakage by catalase and by sodium azide. It was further shown that gossypol is capable of directly producing H2O2. PMID- 1293309 TI - Perfluorooctanoic acid has persistent effects on peroxisome proliferation and related parameters in mouse liver. AB - Male C57Bl/6 mice were treated for 5 days with 0.05% perfluorooctanoic acid (PFOA) in their diet. This treatment resulted in a potent induction of peroxisomal fatty acid beta-oxidation in the liver. In order to investigate recovery from treatment with PFOA, mice were given normal laboratory chow for up to 20 days after termination of PFOA administration. It was established that the activities of peroxisomal lauoryl-CoA oxidase and palmitoyl-CoA oxidation were still elevated 2-3 weeks after termination of treatment. The catalase activity recovered in the cytosolic fraction was also still significantly elevated after 20 days with normal laboratory chow. Furthermore, the protein content of the mitochondrial fraction was increased by PFOA and had not returned to control level at the end of the recovery period. Perfluorooctanoic acid also caused a persistent effect in omega hydroxylation of lauric acid (cytochrome P-452). The activities of cytosolic DT-diaphorase and glutathione transferase were also enhanced by PFOA. However, these two enzymes recovered relatively rapidly from the treatment (2-20 days). This study reveals two different patterns of recovery from PFOA treatment, one involving parameters that recovered completely, or almost completely, from PFOA treatment after 20 days and another involving parameters that were still elevated at the end of the recovery period. PMID- 1293311 TI - Heterogeneity of antibodies to metallothionein isomers and development of a simple enzyme-linked immunosorbent assay. AB - A competitive enzyme-linked immunosorbent assay (ELISA) for the measurement of metallothionein (MT) in tissues and body fluids has been developed. The ELISA employs the IgG fraction of a rabbit antiserum to rat liver Cd-MT-2 polymer, a biotinylated secondary antibody, and peroxidase conjugated avidin. With a 1:4000 dilution of the immunoglobulins, typical standard curves (logit-log regression) provide a linear range of 0.1-100 ng for MT-2 and 10-1000 ng for MT-1. Fifty percent inhibition is accomplished with 15 ng and 250 ng for MT-2 and MT-1, respectively. Rat liver MT-1 and MT-2 containing different metals (Ag, Cu, and Zn) inhibited the antibodies as effectively as CdMT. However, the antibodies exhibited greater affinity for both Apo-MT isoforms. Previously reported discrepancies between results obtained by metal binding assays (e.g., Ag-hem binding) and radioimmunoassay for MT levels in tissues have been largely resolved. By addition of 1% Tween 20 to samples, the ELISA routinely estimated the total MT in samples of rat, mouse, and human liver and kidney at 88% of the value obtained by the silver-hem binding assay. Specific antibodies to MT-2 were purified from our antiserum by affinity purification using CH-Sepharose 4B coupled with rat liver MT-1. Estimation of MT in samples using purified MT-2 antibodies provided slightly lower values (72%) for MT in tissues as compared to the Ag-hem method. The predominant form of MT in tissues of control animals was found to be MT-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293312 TI - Bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene by rat liver bile acid sulfotransferase I. AB - The bioactivation of 7-hydroxymethyl-12-methylbenz[a]anthracene (HMBA) to an electrophilic sulfuric acid ester metabolite has been shown to be catalyzed by rat liver bile acid sulfotransferase I (BAST I). The sulfation and activation of HMBA by BAST I was determined by the ability of sulfated HMBA to form DNA adducts. The BAST I was also shown to react with rabbit anti-human dehydroepiandrosterone sulfotransferase antisera and to represent a major form of hydroxysteroid/bile acid sulfotransferase in female rat liver cytosol. Higher levels of BAST I activity and immunoreactivity as well as HMBA-DNA adduct formation were detected in female rat liver cytosol than in male rat liver cytosol. The bioactivation of HMBA by pure BAST I was dependent on the presence of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the reaction and was inhibited by dehydroepiandrosterone, a physiological substrate for BAST I. Glutathione, a cellular nucleophile with important protective properties, decreased DNA adduct formation in the HMBA sulfation reaction in the absence of glutathione S transferase activity. These results indicate the usefulness of BAST I to investigate the sulfation and activation of HMBA and probably other hydroxymethylated polyaromatic hydrocarbons to electrophilic and mutagenic metabolites under defined reaction conditions. PMID- 1293313 TI - The differential hepatotoxicity and cytochrome P450 responses of Fischer-344 rats to the three isomers of dichlorobenzene. AB - The acute hepatotoxicity and response of hepatic cytochrome P450 to treatment with the three isomers of dichlorobenzene (DCB) have been investigated. The objectives were to estimate the onset of toxicity and to further elucidate the role of cytochrome P450 in the metabolism and toxicity of these compounds. In a study design employing one animal per dose level, Fischer-344 rats were gavaged with up to 25 different dosages, then evaluated 24 h later. Hepatic necrosis, serum alanine aminotransferase, and serum aspartate aminotransferase exhibited similar patterns demonstrating that ortho-DCB (o-DCB) was the most toxic in terms of both earliest onset and degree of response at higher dosages. For these three endpoints, meta-DCB (m-DCB) exhibited a lesser toxicity. Para-DCB (p-DCB) did not cause changes in these three endpoints, but hepatic degenerative changes were found. Total hepatic cytochrome P450 responses were also different after treatment with each isomer. The o-DCB produced a dose-dependent decrease in P450 beginning at dosages lower than the onset of necrosis and appeared to be a suicide substrate for P450. The m-DCB treatment increased P450 at dosages below the onset of necrosis and decreased P450 at higher dosages, with the decline preceding the onset of hepatocyte death. Treatment with p-DCB increased P450 beginning at 380 mg/kg. The combination of toxicity and P450 profiles has provided a framework for interpreting literature data on the metabolism and toxicity of the DCBs in rats. It is also noteworthy that o-DCB and p-DCB were administered at dosages several times the oral rat LD-50 (RTECS) without any lethality. PMID- 1293314 TI - Age-related effects of platelet activating factor (PAF) in the isolated perfused rat heart. AB - Platelet Activating Factor (PAF) is a phospholipid that has been implicated as an important mediator of anaphylactic cardiac dysfunction and involved in the toxic effects of the ischaemia-reperfusion process. In the elderly, these phenomena are thought to be exaggerated by the age-related changes in response to several chemical factors and myocardial ischaemia. We evaluated the effects of PAF (acetyl-o-alkyl-l-phosphatidylcholine) on left ventricular systolic (LVSP) and diastolic (LVDP) pressure, coronary flow rate (CFR) and heart rate (HR) in adult (6 months, AH) and senescent (24 months, SH) rat hearts. The perfusion of PAF (10(-8), 10(-7) and 10(-6) M) induced a concentration-related reduction of LVSP, CFR and HR and a linear increase in LVDP. Contractile modifications were more pronounced in senescent hearts: LVSP decreased (P < 0.01) and LVDP increased with respect to younger animals (P < 0.01 vs. AH). This negative inotropic effect was also present in electrically paced hearts. PAF produced conduction arrhythmias ranging from second-degree atrio-ventricular conduction block to cardiac standstill both in adult and senescent hearts; at a higher dose (10(-6) M), cardiac standstill appeared after 96.5 +/- 15.3 s in adult hearts and after 45.5 +/- 17.6 s in senescent hearts (P < 0.01). Lyso-PAF did not modify while specific PAF antagonist compounds CV-3988 inhibited all electromechanical responses both in adult and senescent hearts. These data suggest that age influences the effect of PAF on contractile parameters, coronary flow and conduction arrhythmias by acting on receptors, whose function is unaffected by age. PMID- 1293315 TI - Changes in work rate to oxygen consumption ratio during hypoxia and ischemia in immature and mature rabbit hearts. AB - This study was designed to evaluate the relative response of myocardial efficiency to reduced oxygen supply (hypoxia and ischemia) in immature and mature isolated rabbit hearts. Hearts were subjected to either 15 min of hypoxia (60% or 30% O2) or reductions in coronary flow to 75%, 50%, 25%, and 15% of basal flow followed by 12 min of total global ischemia and 15 min of reperfusion. In order to examine changes in cardiac efficiency, we utilized the ratio of isovolumic contractile function (rate-pressure product) to myocardial oxygen consumption (RPP/MVO2). Under basal conditions, immature hearts displayed lower aortic pressure. RPP, coronary resistance and RPP/MVO2. Moderate hypoxia (60% O2) resulted in similar reductions in RPP and MVO2 in both age groups, with RPP/MVO2 remaining unchanged. During severe hypoxia, RPP/MVO2 increased significantly in mature hearts but not in immature hearts (P < 0.05). Underperfusion produced greater reductions in RPP and heart rate, whereas reperfusion after ischemia resulted in greater recovery of RPP, dP/dt and MVO2 in immature compared to mature hearts. When oxygen supply was limited by reductions in coronary perfusion. RPP/MVO2 tended to increase in mature hearts, whereas the ratio declined significantly in immature hearts. These data demonstrate that, in this model, a reduction in oxygen supply by hypoxia or hypoperfusion decreases efficiency in immature hearts, but increases efficiency in mature hearts under the same conditions. PMID- 1293316 TI - Physiological growth of arteries in the rat heart parallels the growth of capillaries, but not of myocytes. AB - Maladaption to hemodynamic overload, especially to arterial hypertension, has important clinical implications, and it is necessary to obtain criteria in order to discriminate physiological and pathological growth processes. We investigated the physiological growth of intramyocardial arteries in the rat heart. A new stereological method was introduced to determine the length of intramyocardial arteries from counts on histological sections. Four groups of male Sprague-Dawley rats of different ages were investigated. The growth rate of arteries was characterized by the growth coefficient b according to the exponential function y = axb (allometric growth function). Analysis of left ventricular weights (LVW) and total lengths of left ventricular intramyocardial arteries (L) revealed Lv = constant.LVW0.71 (r = 0.77, P < 0.001). The growth coefficient b < 1 indicates that the arterial supply of the heart, i.e. the length density of arteries Lv (length per unit myocardial volume), decreases during normal growth. Empirically, we found L = constant.LVW-0.28 (r = 0.43, P < 0.01). Previously, we estimated growth rates of b = 0.33 for the total length of left ventricular myocytes and b = 0.71 for the total length of capillaries. Thus, growth of intramyocardial arteries considerably exceeds the length increase of myocytes, but is proportional to the length increase of capillaries. Growth analysis of total mitochondrial volume using historical data of our group revealed proportionality to arteries, as well (b = 0.76). This indicates that growth of arteries and capillaries may be determined by oxygen consumption. PMID- 1293317 TI - The effects of Ca(2+)-free perfusion and the calcium paradox on [125I] endothelin 1 binding to rat cardiac membranes. AB - The binding characteristics of [125I]endothelin-1 (ET-1) to cardiac membranes isolated from rat hearts subjected to Ca(2+)-free perfusion or the Ca2+ paradox were examined. The effect of treatment with 2, 3 butanedione monoxime (BDM), which inhibits the tissue damage associated with the calcium paradox, was also investigated. Membranes from rat hearts perfused under control conditions bound [125I]ET-1 to a single population of sites with a Bmax of 107.7 +/- 3.7 fmol/mg protein and an affinity (KD) of 153 +/- 12 pM. Ten minutes of Ca(2+)-free perfusion resulted in a significant (P < 0.01) increase in Bmax to 167.5 +/- 8.3 fmol/mg protein without change in KD. Ca2+ repletion following Ca(2+)-free perfusion tended to increase further the Bmax (180.6 +/- 10.4 fmol/mg protein) without change in KD. Treatment with BDM attenuated but did not prevent the rise in Bmax following Ca(2+)-free perfusion. Following Ca2+ repletion, however, Bmax returned to control levels in the BDM treated group. These changes were not associated with changes in the ability of ET-1 and ET-3 to inhibit [125I]ET-1 binding. The results demonstrate that Ca(2+)-free perfusion is associated with an increase in the binding site density of [125I]ET-1 which is maintained or further increased upon Ca2+ repletion. If, however, the tissue damage associated with the Ca2+ paradox is prevented with BDM, Ca2+ repletion is associated with a reversal of the increase due to Ca(2+)-free perfusion. PMID- 1293318 TI - The genetic basis of hypertrophic cardiomyopathy. AB - In this article we review the techniques of molecular biology as they apply to the elucidation of the genetic basis of hypertrophic cardiomyopathy. We review the evidence for linkage to chromosome 14 and the specific mutations described to date. The evidence for genetic heterogeneity is presented. We speculate on the pathophysiology of the disease from the perspective of the known molecular defects and review the clinical implications the evolving information may have. PMID- 1293319 TI - Differential growth of neonatal WKY and SHR ventricular myocytes within sympathetic co-cultures. AB - Sympathetic innervation is known to increase heart size in the immature animal, yet the mechanism for this growth remains to be established. This comparative study stereologically quantified the volume of cultured neonatal ventricular myocytes with and without in vitro sympathetic innervation to isolate the mechanisms regulating cardiac growth. Since ventricular myocyte size at birth differs between the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY), we questioned whether SHR myocytes respond differently than WKY myocytes to innervation. Four groups of ventricular myocytes from each strain were compared: myocytes grown alone, myocytes innervated by cultured sympathetic neurons, innervated myocytes exposed to adrenoceptor blockade, and non-innervated myocytes in co-culture dishes. Volumes for the myocyte, nucleus, cytoplasm, mitochondria, sarcomeres and other cellular organelles were assessed within each population and between populations. Relative volumes were determined for the mitochondria, sarcomeres, and other cellular components within the cytoplasm. Innervated WKY myocytes were 38% larger than control myocytes (P < 0.0004). This growth was not blocked by adrenoceptor blockade (P = 0.89 vs. innervated) and was present in the non-innervated myocytes distant from the neurons in the co cultures (P = 0.39 vs. innervated). SHR myocytes were 36% larger than WKY myocytes (P < 0.009) but did not increase with innervation (P = 0.48). SHR myocyte size was also unaffected by adrenoceptor blockade (P = 0.39) or presence of the neurons in the culture dish (P = 0.53). Neonatal WKY ventricular myocyte growth can be provoked in vitro by sympathetic innervation via regulatory mechanisms independent of neuroeffector transmission or anatomic contact, whereas volume of neonatal SHR myocytes is unaltered by sympathetic coculture. These findings are significant for understanding normal as well as aberrant cardiomyocyte growth. PMID- 1293320 TI - [A 13-week subcutaneous toxicity study of prednisolone farnesylate (PNF) in rats]. AB - The toxicity of Prednisolone farnesylate (PNF), a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF was injected subcutaneously at doses of 0.03, 0.3, 3 and 30 mg/kg/day for 13 weeks. In addition, 18.7 mg/kg/day prednisolone (PN), which is approximate to 30 mg/kg/day PNF in prednisolone molarity, was also administered to the rat for comparison. The results are summarized as follows: 1. All animals from the PN 18.7 mg/kg/day group, and four(4) out of ten(10) males and three(3) out of ten(10) females from the PNF 30 mg/kg/day group died having shown weakened condition such as unkempt fur and emaciation. Histopathologically, systemic suppurative inflammation, as shown by pyeronephritis and abscess formation in many organs and tissues, was observed and it was considered that the administration of steroid induced weakened condition and systemic suppuration which resulted in death. In addition, atrophy was noted in the adrenal glands, lymphatic organs and skin, and histopathological lesions were also observed in the lungs, liver, pancreatic islets, bone, bone marrow and mammary glands. 2. Surviving animals in the PNF 30 mg/kg/day group showed almost the same changes as those observed in the dead animals that died. Hematological examination revealed an anemic change and a decrease in lymphocytes with an increase in segmented neutrophils and eosinophils. In the urinalysis and blood chemistry, the changes suggesting damages to the liver and kidneys were mainly observed. 3. In the PNF 3 and 0.3 mg/kg/day groups, several changes such as atrophy of the adrenal glands, lymphatic organs and skin were noted in a dose dependent manner. 4. In the PNF 0.03 mg/kg/day group, ther were no toxic signs. 5. Based on these results, it was concluded that the overt toxic dose of PNF was 0.3 mg/kg/day and the non-toxic dose was 0.03 mg/kg/day in the present study. PMID- 1293321 TI - [A 13-week percutaneous toxicity study of prednisolone farnesylate (PNF) gel in beagle dogs with a recovery period of 5 weeks]. AB - The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Beagle dog. PNF gel was administered percutaneously at doses of 0.2, 0.8 and 3.2 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 2 mg/kg/day prednisolone gel (PN gel), which is approximate to 3.2 mg/kg/day PNF gel in prednisolone molarity, was also administered for comparison. The results are summarized as follows: 1. No deaths were observed in any of the PNF gel test groups or the PN gel group, nor were there any abnormal findings in the clinical signs of the animals. 2. In the hematology, a tendency toward a decrease in the lymphocyte ratio was observed in males from the PNF gel 0.8 mg/kg/day and above groups. In the PN gel group, a significant decrease or a tendency toward a decrease in the lymphocyte ratio was observed, as well as an increase in the white blood cell count in some animals. 3. In the blood biochemistry, a significant decrease or a tendency toward a decrease in total cholesterol and phospholipid was observed in males from the PNF gel 3.2 mg/kg/day group and a tendency toward an increase in triglyceride in females from the PNF gel 3.2 mg/kg/day group was observed. In the PN gel group, a tendency toward an increase in AIP activity, a tendency toward an increase in triglyceride were observed. 4. In the histological examinations, a decrease in the weight of the thymus and adrenal glands, vacuolation of hepatocytes in the middle zone of the liver, atrophy of zona fasciculata of the adrenal glands, hypertrophy of zona glomeruli, swelling of cortical cells of zona faciculate and atrophy of the thymus were observed in the PNF gel 0.8 mg/kg/day and above groups. In the PN gel group, atrophy of submandibular lymph nodes and mesenteric lymph nodes was observed in addition to the same changes as observed in the PNF gel groups. Furthermore, thinning, atrophy or a decrease in the weight of the adrenal glands was also observed both in the PNF gel 3.2 mg/kg/day group and the PN gel group at the end of the 5-week recovery period. 5. As described above, a decrease in the lymphocyte ratio, in the weight of the thymus and adrenal glands and vacuolation of hepatocytes were observed in the PNF gel 0.8 mg/kg/day and above groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293322 TI - [A 52-week percutaneous toxicity study of prednisolone farnesylate (PNF) gel in beagle dogs with a recovery period of 8 weeks]. AB - The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Beagle dog. PNF gel was administered percutaneously at doses of 0.05, 0.2 and 0.8 mg/kg/day for 52 weeks, then the drug was with held for 8 weeks to evaluate reversibility. The results are summarized in the following. 1. In the 0.05 mg/kg/day and above groups, hypotrichosis in the application site of the skin, thinning of the skin and atrophy of the appendages, and in the 0.2 mg/kg/day and above groups a tendency toward retarded body weight gain, were observed. 2. In the 0.2 mg/kg/day and above groups, a drop in the lymphocyte ratio, a rise in GOT activity and A1P level, and in the 0.8 mg/kg/day group a rise in free fatty acid were observed. 3. In the 0.2 mg/kg/day group and above groups, atrophy of the zona fasciculata and zona reticularis were observed. In the 0.8 mg/kg/day group, a decrease in the weight of the thymus and adrenal glands, and a increase in the weight of the liver, were observed. 4. At the end of the recovery period, most of the changes disappeared, except for those in the adrenals and treated area. From the above results, under the conditions of this study, it was concluded that when the changes observed in the application site of the skin in each group were not taken into consideration, the toxicological no effect level was 0.05 mg/kg/day for both males and females and the overt toxic dose level was 0.8 mg/kg/day. PMID- 1293323 TI - [Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)- study by subcutaneous administration of PNF prior to and in the early stages of pregnancy in rats]. AB - A fertility study of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, was conducted in Sprague-Dawley rats. This compound was administered subcutaneously at dose levels of 0(control), 0.04, 0.2 and 1 mg/kg/day to males for 63 days before mating and during the mating period, and to females for 14 days before mating, through the mating period and until day 7 of pregnancy. Each 24 male and female rats were mated, and females were killed on day 20 of pregnancy to examine their fetuses. 1. In the parental animals, loss of fur or thin fur and incrustation of treated site occurred in male rats treated at doses of 0.2 mg/kg or more and female rats treated at dose of 1 mg/kg, and at the same dose groups, the thinning of skin, atrophy of the thymus and intention of the substance at the injected site were noted. Moreover, body weight gains and food consumption were suppressed in both sexes treated at the dose of 1 mg/kg. 2. Fertility and reproductive ability in both sexes, and estrus cycles in female rats were not affected by administration of PNF. 3. In the fetuses, no embryonic or fetal lethal effect and teratogenic effect were noted. From these results, the no-effect dose levels of PNF on the parental general states, the parental reproductive ability and those of the fetuses are thought to be 0.04 mg/kg/day, 1 mg/kg/day or more and 1 mg/kg/day or more, respectively, under the experimental conditions of this study. PMID- 1293325 TI - [Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)- teratogenicity study in rabbits by subcutaneous administration]. AB - The effect of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, on fetal development of the rabbit was studied. PNF was administered subcutaneously at dose levels of 0(control), 0.01, 0.05 and 0.25 mg/kg/day during the fetal organogenesis period. In the pregnant animals, PNF caused no abnormalities in clinical sign, body weight gain, food consumption, or autopsy findings at 0.01 and 0.05 mg/kg/day groups; the animals at 0.25 mg/kg/day group showed a reduction in body weight gain and food consumption. Two of 13 animals at 0.25 mg/kg/day group aborted. And hydrothorax, mucosal hemorrhage of the stomach, or fading of the liver were observed in some animals. In the fetuses, PNF was observed no abnormalities in external, visceral, or skeletal examination; slight increase of embryofetal mortality, or reduction of live fetal body weight and placental weight were observed at 0.25 mg/kg/day. The results suggest that the non-effective dose level of PNF is 0.05 mg/kg/day for pregnant females in general and reproductive toxicity, and for fetuses under the condition of this study. PMID- 1293324 TI - [Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)- study by subcutaneous administration of PNF during the period of fetal organogenesis in rats]. AB - A teratogenicity study of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, was conducted in Sprague-Dawley rats. This compound was administrated subcutaneously to female rats at dose levels of 0(control), 1, 5 and 25 mg/kg/day, once a day, for 11 days from day 7 to day 17 of pregnancy. In each dose group, 26 or 27 dams were killed on day 20 of pregnancy to examine their fetuses. The remaining 14 or 15 dams of each group were allowed to litter naturally, and observations were made on the postnatal growth and development of their offspring. 1. In the dams treated at doses of 1 mg/kg or more, decreased body weight gains and food consumption and retention of the substance at the injected site were noted. However, general signs, parturition, lactation and nursing behaviors were not affected by the administration of PNF. 2. In the F1 fetuses, no embryonic or fetal lethal effect, fetal retardation and teratogenic effect were noted. 3. In the F1 newborns, the postnatal growth, development, responses, behaviors, learning ability and reproductive ability were not influenced. Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were detected. From these results, the no-effect dose levels of PNF on the parental general states, the parental reproductive ability and those of the F1 offspring are thought to be less than 1 mg/kg/day, 25 mg/kg/day and 25 mg/kg/day, respectively, under the experimental conditions of this study. Moreover, the F2 fetuses are not affected by doses up to 25 mg/kg/day of PNF. PMID- 1293327 TI - [Mutagenicity studies of prednisolone farnesylate (PNF)]. AB - Prednisolone farnesylate (PNF) was tested for mutagenicity by Ames test using Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2 uvrA), for clastogenic activity in vitro by the chromosomal aberration test in a Chinese hamster fibroblast cell line (CHL), and for induction of micronuclei by the micronucleus test in male ICR mice. 1) In Ames test, PNF with and without metabolic activation showed no mutagenicity in any strains at any dose levels (312-5,000 micrograms/plate). 2) In the chromosomal aberration test, PNF with metabolic activation produced a slight increase in the incidence of structural chromosomal aberrations in CHL cells at 1,500 micrograms/ml. 3) In the micronucleus test, a single administration of PNF caused no significant increase of micronucleated polychromatic erythrocytes at any doses (250-2,000 mg/kg). PMID- 1293326 TI - [Reproductive and developmental toxicity study of prednisolone farnesylate (PNF)- study of subcutaneous administration of PNF during the perinatal and lactation periods in rats]. AB - The effects of Prednisolone farnesylate (PNF), a newly synthesized corticosteroid, administrated during the perinatal and postnatal periods were studied in Sprague-Dawley rats. This compound was injected subcutaneously to female rats at dose levels of 0(control), 0.05, 0.5 and 5 mg/kg/day, once a day, for the period from day 17 of pregnancy to day 21 after parturition. Twenty-two to 25 dams in each dose group were allowed to litter naturally, and observations were made on the postnatal growth and development of their offspring. 1. In the dams treated at doses of 0.5 and 5 mg/kg, decreased body weight gains, atrophy of the thymus and retention of the substance at the injected site were noted. However, general signs, food consumption, parturition, lactation and nursing behaviors were not affected by the administration of PNF. 2. In the F1 newborns, the postnatal growth, development, responses, behaviors, learning ability and reproductive ability were not influenced. Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were detected. From these results, the no effect dose levels of PNF on the parental general states, the parental reproductive ability and those of the F1 offspring are thought to be 0.05 mg/kg/day, 5 mg/kg/day or more and 5 mg/kg/day or more, respectively, under the experimental conditions of this study. Moreover, the F2 fetuses are not affected by doses up to 5 mg/kg/day of PNF. PMID- 1293328 TI - [Effects of prednisolone farnesylate (PNF) gel on skin and ocular mucosa]. AB - Various tests for irritation, phototoxicity, contact sensitivity and photocontact sensitivity of PNF gel were conducted. The results were as follows. 1) In the primary dermal irritation test and trypan blue test, slight erythema was noted in the rabbits treated with 0.8 and 1.6% PNF gel, although similar reaction occurred in those treated with the base. 2) In the test for the primary irritation to the ocular mucosa, severe irritant reactions were caused by 0.8 and 1.6% PNF gel and its base. However these reactions disappeared 7 days after irritation. 3) In the phototoxicity test and contact sensitivity test, no positive reactions were detected by 0.8 and 1.6% PNF gel. On the other hand, in the photocontact sensitivity test, positive reaction were noted in the guinea pig treated with 0.8 and 1.6% PNF gel and its base. PMID- 1293329 TI - [Mammalian toxicity of empenthrin (Vaporthrin, S-2852F)]. AB - 1. Acute toxicity: Empenthrin ((RS)-(EZ)-1-ethynyl-2-methyl-2-pentenyl (1R) cis/trans-chrysanthemate) caused some toxic signs such as muscular fibrillation, tremor, hypersensitivity, decrease of spontaneous activity, ataxic gait, lymb paralysis, irregular respiration, excretion of oily substance, loose stool and urinary incontinence in oral acute toxicity studies at 1000 mg/kg and above in rats, and at 2000 mg/kg and above in mice. The oral LD50 value was estimated greater than 5000 mg/kg (male) and greater than 3500 mg/kg (female) in rats and greater than 3500 mg/kg (both sexes) in mice. In both rats and mice, the toxic signs were not found at 2000 mg/kg by dermal administration. The dermal LD50 value was estimated greater than 2000 mg/kg (both sexes) in both rats and mice. The LC50 value in rats for the acute inhalation toxicity of empenthrin was estimated to be greater than 4610 mg/m3 for both sexes. The LC50 value in mice was determined to be 2700 mg/m3 for male and 2300 mg/m3 for female. Mice showed higher sensitivity to empenthrin than rats. 2. Reproductive and developmental toxicity: Empenthrin was orally administered to fetal organogenesis periods of rats at the dose levels of 50, 150 and 500 mg/kg, and of rabbits at 100, 300 and 1000mg/kg. Maternal toxicity was found at 500 mg/kg in rats and at 300 mg/kg or more in rabbits. There were no teratogenicity, no embryotoxicity and no fetal retardation in rats or rabbits. In addition, there were no adverse effects on F1 pups growth, development or reproductive performance. 3. Subchronic toxicity: Empenthrin was orally administered to male and female SD rats at dose levels of 0 (corn oil), 10, 100 and 300 mg/kg for 26 weeks. Clinical signs, body weight, food and water consumption were monitered, and hematological, blood biochemical, ophthalmological and histopathological examination were carried out. As a result, changes related to administration of empenthrin were observed mainly in the liver and kidneys in rats receiving 100 mg/kg or more. Therefore, the no-effect-level of empenthrin is determined to be 10 mg/kg in both sexes of rats in this study. PMID- 1293330 TI - [A 13-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 5 weeks]. AB - The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel (PN gel), which is approximate to 16 mg/kg/day PNF gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the PNF gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum AIP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the PNF gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of PNF gel, there were no toxic signs induced by the drug. 4. In the PN gel 10 mg/kg/day group, drug-related changes were almost similar to those of the PNF gel group, but the severity of the lesions was stronger than in the PNF gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of PNF gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study. PMID- 1293332 TI - [Nursing, from feminist theory perspective. 1. Evolution of feminist theories]. PMID- 1293331 TI - [A 52-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 8 weeks]. AB - The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.125, 0.5 and 2.0 mg/kg/day for 52 weeks, then the drug was withdrawn for 8 weeks to evaluate the reversibility. The results are summarized as follows: 1. In the PNF gel 2.0 mg/kg/day group, thinning of the skin at the application site, slightly retarded body weight gains, a tendency toward a decrease in the white blood cell count, an elevation of serum GOT and GPT activity, free fatty acid level, and a decrease in alpha 1-globulin fraction were observed. In the pathological examinations, decreased organ weights of the thymus, spleen and adrenal glands, and thinning of the skin were observed. Histopathological examination revealed atrophy of the thymus and zona fasciculata of the adrenal glands, thinning of the skin with atrophied skin appendages, and hepatocellular hypertrophy with hypertrophied uncleus in the perilobular zone. 2. In the PNF gel 0.5 mg/kg/day group, thinning of the skin at the application site and a decrease in alpha 1-globulin fraction were observed. Histopathologically, thinning of the skin atrophied skin appendages was observed. 3. In the PNF gel 0.125 mg/kg/day group, there were no toxic signs induced by the drug. 4. After the 8-week recovery period, the changes in the skin were observed in the 2.0 mg/kg/day group, but the severity was lowered. The other changes disappeared and so it was demonstrated that the changes were reversible. 5. Based on these results, it was concluded that the overt toxic dose of PNF gel was 0.5 mg/kg/day and the non-toxic dose was 0.125 mg/kg/day in the present study. PMID- 1293333 TI - [Nursing, from feminist theory perspective. 2. Approaches to feminist analysis]. PMID- 1293334 TI - [Nursing, from feminist theory perspective. 3. Feminism and nursing: redefining the issues]. PMID- 1293335 TI - [Nursing, from feminist theory perspective. 4. Envisioning possibilities: applying feminist principles to the issues]. PMID- 1293336 TI - [Nursing, from feminist theory perspective. 5. Feminist principles in practice]. PMID- 1293337 TI - [Nursing, from feminist theory perspective. Feminist pedagogy in nursing education]. PMID- 1293338 TI - [Blood group determination during pregnancy]. PMID- 1293339 TI - [Improvement of cooperation between maternity care stations and delivery hospitals]. PMID- 1293340 TI - [Mother-Child Development Project report]. PMID- 1293341 TI - [The midwife is always needed]. PMID- 1293342 TI - [Dear midwives!]. PMID- 1293343 TI - [No one knows everything--not even a mother]. PMID- 1293344 TI - [Constriction of the left main coronary artery. Early and long term treatment outcome]. AB - Clinical presentation and course were studies in 45 consecutive patients (p)--39 males, 6 females with angiographically proven left main coronary artery stenosis (LMCA) > 50%. Mean age was 54.7 years. Three (6%) had no history of chest pain, 2 p (4%) had atypical chest pain, and the remaining (90%) had typical angina pectoris. 19 p (42%) had unstable angina, 20 p (44%) had suffered a myocardial infarction in the past. Outside an episode of chest pain most of the patients had an abnormal ECG with ST-T segment depression 2 mm or more in leads V3-6 and ST-T elevation in leads V1 and aVR. No significant differences were found when the abnormalities of the ST-T segment were compared to severity of LMCA obstruction. A symptom limited exercise test was performed in 17 (37%) p. It was abnormal in 13 p (29%). Thirty eight patients (85%) underwent bypass surgery and the mean number of bypass graft was 3.3. Seven patients were treated medically. In the surgical group four p (10.5%) died perioperatively. All of them had subtotal occlusion of LMCA, without significant lesions in the remaining coronary arteries, the ejection fraction (EF) was above 66%. Among thirty four living patients thirty have been asymptomatic. In the medically treated group 3 p (42%) died and only two of four survivors were asymptomatic at a mean follow-up 35.7 months. Left ventricle of all died patients were severely damaged (EF mean 28%), right coronary artery (RCA) was totally occluded and all had rythm disturbances. We conclude, that patients with significant LMCA stenosis had a good prognosis when treated surgically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293345 TI - [Sinus node in patients with atrioventricular and interventricular blocks. Electrophysiologic evaluation]. AB - To assess the function of the sino-atrial node, electrophysiological study with pharmacological autonomic blockade was performed in 3 groups of patients: group I with a-v III zero or II zero type 2 heart block, group II with bifascicular interventricular blocks and group III-controls. Sino-atrial node electrogram was recorded in 81% of patients. Obtained results show, that sino-atrial node dysfunction is uncommon in patients with atrioventricular or interventricular blocks (8.6% and 15% respectively). Electrophysiological assessment of sino atrial node function seems to be important in the consideration of patients with a-v or interventricular blocks for appropriate type of permanent pacing. PMID- 1293346 TI - [Echocardiographic test of dipyridamole in recognition of coronary artery disease]. AB - To assess the feasibility, safety and usefulness of dipyridamole stress echocardiography for the detection of coronary artery disease we evaluated 194 patients (124 men, 70 women) with effort chest pain. All patients underwent electrocardiographic submaximal bicycle exercise testing and 2-dimensional echocardiography after dipyridamole injection. Echocardiographic test was considered positive when new wall motion abnormalities were observed after dipyridamole i.v. injection (0.56 mg/kg b.m.). Sensitivity and specificity of electrocardiographic exercise test and dipyridamole stress echocardiography were assessed in 37 persons who underwent selective coronary angiography. The sensitivity and specificity of dipyridamole stress echocardiography, were respectively 85.0% and 91.7% and were higher than those of exercise electrocardiography. 2-dimensional echocardiography after dipyridamole injection is a well tolerated, feasible and effective test in the diagnosis of coronary artery disease. PMID- 1293347 TI - [Heart transplantation in the doctors' opinion (results of a questionnaire)]. AB - This report presents the results of the survey aimed to evaluate physicians' attitude and personal opinion on heart transplantation. The study comprised 124 people: 92 physicians (internal medicine) and 32 students of the Faculty of Medicine (sixth year) in Cracow. None of the responders was directly or indirectly involved in cardiac transplantation. Responders were assessed using questionnaire consisting of 17 questions. Participation was voluntary and anonymous. Percentage analysis and non-parametric chi-2 test were applied in statistical analysis of the results. As many as 91.9% responders declared themselves as heart transplantation supporters. As the most important causes of small number of heart transplantations in Poland the following factors were considered: inadequate quantity of cardiosurgical centers and qualified medical staff (72%), shortage of heart donors (53%), insufficient knowledge of the physician on donor's qualification (49%), excessive cost of transplantation and postoperative management (46%). Only 11.3% responders have chosen right criteria for brain death out of given possibilities, 4% identified the factors excluding potential heart donors, 89.5% have known who was authorized to diagnose brain death and 59.6% knew where to refer the donor. The fact that after cardiac transplantation the patient requires long-term immunosuppressive treatment was recognized by 87%. Only 8.3% was able to indicate the essential drug - cyclosporin A, whereas 56.1% of responders were willing to treat the patients after heart transplantation. No statistical correlation between the above mentioned results and the place of work, degree of specialization, professional experience of the physician was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293348 TI - [Two-dimensional transesophageal echocardiography (clinical value)]. AB - The introduction of two-dimensional echocardiography (echo 2D) complemented by doppler techniques has allowed to assess the dynamic function of the heart. However in 10-15% patients the standard transthoracic method (TEE) does not provide complete echocardiographic image due to obesity, emphysema and deformations of thorax. These difficulties have been later overcome by transesophageal probe, but it made the examination possible only in one plane monoplane TEE (m-TEE). Transesophageal echocardiography the biplane probe (bi TEE), introduced in late 80s has permitted the heart and aorta visualization in two perpendicular planes: transverse (T) and longitudinal (L). The purpose of our study was to establish the diagnostic value of biplane transesophageal echocardiography in comparison with hitherto existing monoplane echocardiography (transverse plane). The study group consists of 60 patients (aged 19-78 years) with various diseases of heart and aorta. We performed biplane transesophageal examinations with the use of Aloka SSD-870 echocardiograph connected with the biplane probe (45 patients) or new, prototypical matrix probe (15 patients). For the heart and aorta assessment the typical projections were used. The advantages of biplane TEE compared with monoplane TEE are as follows: 1) more favorable left ventricular examination, 2) better assessment of the heart apex, 3) the ability to investigate the right heart; tricuspid valve, right ventricular outflow tract, pulmonary valve, pulmonary trunk and right pulmonary artery, 4) precise imaging of both atrial' structures: cavities, intraatrial septum, foramen ovale, left atrial appendage, venae cavae and pulmonary veins, 5) possibility of thoracic aorta diagnostics, especially in ascending aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293349 TI - [Vital recognition of complete occlusion of the left main coronary artery]. AB - Left main coronary artery occlusion is found in about 0.05% of all coronary arteriograms. In this case report left main occlusion was associated with a dominant right coronary artery and good collaterals to the circumflex and left anterior descending coronary arteries, which seems to be essential for survival in this lesion. Our case belongs to the minority of patients who have survived a myocardial infarction in the presence of left main occlusion. PMID- 1293350 TI - [Angiotensin converting enzyme inhibitors. Increasing importance in the treatment of hypertension]. PMID- 1293351 TI - [Automatic implanted cardioverter-defibrillators (AICD)]. PMID- 1293352 TI - [M. Mirowski--co-originator of the implantable cardioverter-defibrillator]. PMID- 1293353 TI - [The physiological importance of the micro-flora of the digestive system]. PMID- 1293355 TI - [Standard of care for transurethral urinary catheterization. Standard of care for nursing schools or the didactic standard of care]. PMID- 1293354 TI - [The practical transformation of pathophysiological findings in the development of decubitus ulcers]. PMID- 1293357 TI - [Laparoscopic appendectomy]. PMID- 1293356 TI - [Septicemia in the newborn]. PMID- 1293358 TI - [Surgery through a key hole. New minimally invasive surgery. Tiny sewing machine instead of clips]. PMID- 1293359 TI - [The trouble with dental prostheses]. PMID- 1293360 TI - [Sleep disorders: various sleeping pills are individually adjusted to provide an undisturbed night's rest]. PMID- 1293361 TI - [Highly motivated]. PMID- 1293362 TI - [Dying and death in the intensive care unit. Strategies for survival for the daily showdown]. PMID- 1293363 TI - [Dealing with death]. PMID- 1293364 TI - [Bed to bed]. PMID- 1293365 TI - [Good topics--reread. Resolutions by the German Surgical Society on the treatment of the terminally ill and the dying]. PMID- 1293366 TI - [Neurologic rehabilitation in older patients--with special regard to stroke]. PMID- 1293368 TI - [Possibilities and limitations of endoscopic surgery]. PMID- 1293367 TI - [Laser therapy of dermatologic diseases]. PMID- 1293369 TI - [Tasks in the care of breast neoplasms]. PMID- 1293370 TI - [Prevention of thromboembolism]. PMID- 1293371 TI - [Bitter complaints at Wildbad]. PMID- 1293372 TI - [Rules for medical devices--what improvements for patients and users developed?]. PMID- 1293373 TI - [Therapeutic possibilities for hand dysfunctions in cerebral paralyses]. PMID- 1293374 TI - [Ascites: pathophysiology, clinical aspects and therapeutic effectiveness]. PMID- 1293375 TI - [Wounds and their treatment]. PMID- 1293376 TI - [Dental continuing education for the nursing personnel]. PMID- 1293377 TI - [Non-professional activities--do they exist?]. PMID- 1293378 TI - [Hygiene hints: eggs]. PMID- 1293379 TI - X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation. AB - Three female patients are described with pyruvate dehydrogenase (PDH) deficiency as a result of mutation in the X-linked gene for the E1 alpha subunit of the complex. Two of these patients illustrate typical presentations of PDH E1 alpha deficiency, with severe neurological dysfunction, degenerative changes and developmental anomalies in the brain, together with variable lactic acidosis. The third patient extends the known spectrum of the condition to include mild to moderate mental retardation and seizures in an adult. All three patients have the same mutation in the PDH E1 alpha gene. This mutation, a C-to-T substitution in a CpG dinucleotide in amino acid codon 302 (designated R302C), results in the replacement of arginine by cysteine at this position. The mildly affected adult was the mother of one of the other patient, making this the first described instance of mother-to-daughter transmission of a mutation causing PDH E1 alpha deficiency. The genetic basis of the variable expression of X-linked PDH E1 alpha deficiency in heterozygous females is discussed. PMID- 1293380 TI - Hypertrophic obstructive cardiomyopathy in a neonate with the carbohydrate deficient glycoprotein syndrome. AB - The carbohydrate-deficient glycoprotein (CDG) syndrome in its most severe form (neonatal olivopontocerebellar atrophy) is a life-threatening multisystem disease. We report a neonate who was referred for cardiological assessment because of respiratory distress, a murmur and episodes of desaturation. After initial spontaneous improvement he presented at 9 weeks with evidence of a severe hypertrophic obstructive cardiomyopathy (HOCM). The diagnosis of CDG syndrome was suggested by the characteristic dysmorphic features, hypotonia, visual inattention and severe failure to thrive; it was confirmed by electrophoresis of serum transferrin. HOCM can be a feature of the CDG syndrome, in addition to the (previously reported) pericardial effusions. PMID- 1293381 TI - Autoimmune thyroiditis in a case of tyrosinaemia type III. PMID- 1293382 TI - Isolated biotin-resistant deficiency of 3-methylcrotonyl-CoA carboxylase presenting as a clinically severe form in a newborn with fatal outcome. AB - The son of Kurdish, consanguineous parents (cousin marriage) presented from the first day of life with initially focal and later generalized attacks of epileptic seizures and a severe generalized muscular hypotonia. Urinary excretion of 3 hydroxyisovalerate and of 3-methylcrotonylglycine was persistently increased. Diagnosis of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency was confirmed in cultured fibroblasts. Psychomotor retardation was progressive, seizures and marked EEG abnormalities persisted. Treatment with leucine and protein-resistricted diet under hospital control did not significantly improve these conditions. The patient died from a cardiac and circulatory failure after a prolonged epileptic attack, with bronchial aspiration. The non-responsiveness of our patient to therapy and the fatal outcome indicate the existence of a severe neonatal variant of this otherwise rather benign genetic enzyme deficiency. PMID- 1293383 TI - Glycogen debranching enzyme deficiency: long-term study of serum enzyme activities and clinical features. AB - In glycogen storage disease type III (glycogen debranching enzyme (DE) deficiency), the activities of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase may be strikingly elevated during childhood but are low during adult life. To determine the pattern of the elevated serum enzyme activities in relationship to diet, the biochemical subtype and clinical symptoms, 13 patients with DE deficiency were studied. Activities of serum aspartate and alanine transaminases, lactate dehydrogenase, and alkaline phosphatase were markedly elevated during infancy. Continued elevation of enzyme activities during childhood appeared to be related to DE deficiency in liver, but unrelated to DE deficiency in muscle. Activity elevations correlated inconsistently with diet and poorly with childhood growth rate or the presence of hypoglycaemia. The serum enzyme activities declined around puberty concomitantly with a decrease in liver size. Although periportal fibrosis and micronodular cirrhosis indicated the presence of hepatocellular damage during childhood, the decline in serum enzyme activities with age and the absence of overt hepatic dysfunction suggest that the fibrotic process may not always progress. PMID- 1293384 TI - Hereditary xanthinuria and Ehlers-Danlos syndrome. PMID- 1293385 TI - Differential diagnosis of hydroxydicarboxylic aciduria based on release of 3H2O from [9,10-3H]myristic and [9,10-3H]palmitic acids by intact cultured fibroblasts. AB - Intact cultured fibroblasts from patients with deficiency of long-chain 3 hydroxyacyl-CoA dehydrogenase release 3H2O from [9,10-3H]myristic acid and [9,10 3H]palmitic acid more slowly than normal. The ratio of activity (palmitate/myristate) is also low and the expression (rate with palmitate2/(rate with myristate) gives good differentiation between affected and unaffected cells. In some patients who have shown hydroxydicarboxylic aciduria when unwell there is reduced 3H2O production from [9,10-3H]myristic and [9,10-3H]palmitic acids by intact cultured fibroblasts but normal 3-hydroxyacyl-CoA dehydrogenase activities in disrupted cells. The palmitate/myristate ratio is higher than in long-chain 3 hydroxyacyl-CoA dehydrogenase deficiency. The basic defect in these patients is still unknown but it is suggested that caution be used over the administration of medium-chain triglyceride. PMID- 1293386 TI - Methylmalonic aciduria and sudden child death. PMID- 1293387 TI - Long-term effects of bone marrow transplantation on lysosomal enzyme replacement in beta-glucuronidase-deficient mice. AB - This study uses bone marrow transplantation (BMT) between congenic strains of mice as an experimental model to examine enzyme replacement therapy of lysosomal storage diseases. Bone marrow cells from donor mice which have normal levels of the lysosomal enzyme beta-glucuronidase (Gus), which is heat-stable, rapidly repopulated the haematopoietic compartment of irradiated recipient mice which have only low levels of a thermolabile form of this enzyme. Gus activity was found to increase progressively in the tissues of the recipients, including the liver, heart and skeletal muscle. Elevated levels were also observed in the kidney and brain. The increase in enzyme activity in the host tissues was not due to the presence of contaminating blood cells, but rather to the acquisition of new, heat-stable enzyme from the donor bone marrow cells. High levels of Gus activity persisted for at least 72 weeks, showing the potential therapeutic value of BMT for enzyme deficiency diseases. PMID- 1293388 TI - Bone marrow transplantation for Sanfilippo disease type B. AB - Allogeneic bone marrow transplantation was performed on twins with Sanfilippo B disease. They were the first two patients with this disorder to undergo the procedure. There was definite evidence of engraftment as shown by conversion to donor blood group antigen and tissue type, and increased leukocyte alpha glucosaminidase activity. Nine years post transplant, neither twin is as handicapped as her untreated brothers were at the same age, although in one twin hyperactivity and behavioural problems, characteristic of the disorder, are present. Details of the twins' intellectual development and growth, their alpha glucosaminidase activity and urinary glycosaminoglycan excretion are reported. PMID- 1293389 TI - Bone marrow transplantation for Niemann-Pick type IA disease. AB - Bone marrow transplantation has been undertaken with encouraging results as therapy for a wide variety of lysosomal storage diseases. We report a case of Niemann-Pick disease Type IA in which, despite the presence of only mild hypotonia with depressed reflexes, the clinical course of the disease appeared to be only slightly modified by this procedure, which was performed at the earliest practical opportunity. The patient was diagnosed early when asymptomatic, because of a family history of an affected sibling who died at 14 months. He received a bone marrow transplant from an HLA-identical, MLC non-reactive sibling donor, whose leukocyte sphingomyelinase activity was in the homozygote normal range. There was adequate engraftment as evidenced by persistently normal leukocyte sphingomyelinase activities, and there was no evidence of graft-versus-host disease. Visceral storage and neurological impairment were less rapidly progressive than in his untreated sibling but he eventually died at 30 months. Autopsy confirmed that this was essentially due to the effects of the underlying Niemann-Pick disease. We conclude that despite some success in other neurovisceral lysosomal storage disorders, bone marrow transplantation is not likely to be an adequate treatment for Niemann-Pick disease Type IA. PMID- 1293390 TI - Carotenaemia with low vitamin A levels and low retinol-binding protein. PMID- 1293392 TI - Aspartylglycosaminuria presenting with hepatosplenomegaly in early infancy. PMID- 1293391 TI - Rhizomelic chondrodysplasia punctata--a new clinical variant. PMID- 1293393 TI - Thyrotoxic periodic paralysis in a Saudi Arab. PMID- 1293394 TI - 5-Oxoprolinuria due to glutathione synthetase deficiency. PMID- 1293395 TI - Estimates of uridine diphosphate glucose in human erythrocytes. PMID- 1293396 TI - D-glyceric aciduria: new development. PMID- 1293397 TI - Selective killing of cells with oxidative defects in galactose medium: a screening test for affected patient fibroblasts. PMID- 1293398 TI - Urinary screening for alpha-OH triazolam by FPIA and EIA with confirmation by GC/MS. AB - Triazolam is a very short-acting triazolobenzodiazepine with sedative-hypnotic properties. Approximately 2% of an oral dose is excreted unchanged in the urine. The major urinary metabolite is alpha-hydroxytriazolam glucuronide (70% of the dose). The objective of this study was to characterize the reactivity of alpha hydroxytriazolam in the urine benzodiazepine assay by fluorescence polarization immunoassay (FPIA; Abbott TDx) in comparison with enzyme immunoassay (EIA; Syva EMIT d.a.u. benzodiazepine assay). alpha-OH triazolam at 300 ng/mL gave a response equivalent to the 200-ng/mL nordiazepam Abbott calibrator. In the EMIT assay, alpha-OH triazolam gave a response equivalent to the 300-ng/mL calibrator (Syva) at 100-200 ng/mL. Both immunoassays gave positive results in 9 out of 9 urine specimens collected from individuals receiving triazolam. Confirmation was performed by analyzing for alpha-OH triazolam after enzymatic hydrolysis and formation of a TMS derivative for GC/MS. All urine specimens were positive for alpha-OH triazolam. In conclusion, both the FPIA and EIA immunoassay screening assays are acceptable for detecting the presence of alpha-OH triazolam in the urine of patients receiving therapeutic doses of triazolam. PMID- 1293399 TI - Isolation of acidic, neutral, and basic drugs from whole blood using a single mixed-mode solid-phase extraction column. AB - A solid-phase extraction procedure was developed for the isolation of acidic, neutral, and basic drugs from whole blood. A blood sample was sonicated, diluted with phosphate buffer, and the drugs were extracted on a mixed-mode bonded-phase silica column at pH 6.0. The extraction system was adjusted to pH 3.3 with acetic acid. After column drying, the drugs were selectively eluted from the column by two different eluates, which were collected separately. Acidic, neutral, and weakly basic drugs with lower pKa values (e.g., benzodiazepines) were present in the first acetone-chloroform (1:1) fraction. The other basic drugs were present in the second fraction (basic ethyl acetate). The drugs with pKa's close to the pH of the extraction system (pH 3.3) appeared in both fractions. The two fractions were evaporated until approximately 100 microL of solvent remained in the tube and were then analyzed on a gas chromatograph equipped with a wide-bore capillary column and flame ionization detector. The absolute recoveries of all tested drugs exceeded 81% at a concentration of 2 micrograms/mL. PMID- 1293400 TI - Gas chromatographic determination of propylene glycol dinitrate in rodent skin. AB - A gas chromatographic (GC) method was developed for the detection of propylene glycol dinitrate (PGDN) in rodent skin following extraction with ethyl acetate. Known quantities of PGDN contained in the torpedo fuel Otto Fuel II were added to homogenates of rat skin, which were subsequently extracted with two 10-mL portions of ethyl acetate. An aliquot of each extract was analyzed by GC with a flame ionization detector. With this method, concentrations ranging from 0.0042 to 11.2 mg/mL were determined by comparison with a standard curve. The extraction efficiencies ranged from 85.7% for the lowest concentration to 101% for the highest concentration. PMID- 1293401 TI - Quantitation of cinnamaldehyde and cinnamic acid in blood by HPLC. AB - A rapid and sensitive high performance liquid chromatographic (HPLC) method is described for the quantitation of cinnamaldehyde (CNMA) in rat blood at concentrations of 0.1-100 micrograms/mL. One of the metabolites of CNMA, cinnamic acid, can also be quantified simultaneously. CNMA is unstable in rat blood, probably because of rapid oxidation to cinnamic acid by enzymatic catalysis and nonenzymatic Schiff base formation with free amine groups of blood proteins. The disappearance of CNMA from rat blood follows first-order reaction kinetics with a half-life of 9 min at room temperature. The current analysis method involves the addition of an agent that will prevent CNMA degradation by denaturing protein and competitively blocking nucleophilic addition reactions, resulting in the nearly complete recovery of CNMA from blood. Recovery of cinnamic acid was approximately 80% at concentrations of 1-10 micrograms/mL. PMID- 1293402 TI - Confirmation of low concentrations of urinary benzodiazepines, including alprazolam and triazolam, by GC/MS: an extractive alkylation procedure. AB - Urine samples containing diazolo- and triazolobenzodiazepines and metabolites were hydrolyzed with beta-glucuronidase and extracted with methylene chloride. The extracts were treated with methyl iodide, methylene chloride, and tetrahexylammonium hydrogen sulfate in basic solution to form the methyl derivatives of the drugs and metabolites. GC/MS analysis resulted in the following test characteristics: day-to-day precision at 360 ng/mL (120 ng/mL for the triazolobenzodiazepine metabolites) was 2.4 to 5.5% CV; calibration curves were linear to 6000 ng/mL (1000 ng/mL for the triazolobenzodiazepine metabolites), and operational limits of quantitation were in the range 13-25 ng/mL. PMID- 1293403 TI - Emit ETS plus ethyl alcohol assay for the determination of ethanol in human serum and urine. AB - We evaluated the enzymatic Emit ETS Plus Ethyl Alcohol Assay (Emit) intended for the quantitative analysis of ethanol in human urine, serum, and plasma. The assay had been designed for use with the new Syva ETS Plus analyzer. The assay had a linear range up to 6.5 g/L and a low detection limit of 0.1 g/L. Assay within-run precision in serum with ethanol added to 0.25, 0.40, 1.00, 3.00, and 5.00 g/L yielded CVs (n = 32) of 6.1, 5.8, 3.7, 3.5, and 4.5%, respectively. Within-run precision of the assay using with ethanol added to 0.25, 0.40, 1.00, 3.00, and 5.00 g/L yielded CVs (n = 32) of 4.9, 5.0, 4.3, 3.3, and 5.0%, respectively. Between-run precision of aqueous controls yielded 0.41 +/- 0.02 g/L ethanol (target value, 0.40 g/L), CV = 4.5% (n = 31) and 3.05 +/- 0.06 g/L ethanol (target value, 3.00 g/L) CV = 2.1% (n = 31). Absolute recovery of the assay with 0.40 to 6.00 g/L ethanol added to serum and urine yielded mean recovery values of 105.5 and 101.5%, respectively. Results of the analysis of patient serum and urine specimens for ethanol by the Emit assay correlated well with those obtained by other methods. The Emit assay was found to be rapid, precise, and accurate for the determination of ethanol in clinical specimens. It was also found to be free of interferences from small molecular weight alcohols, aldehydes, ketones, and glycols. The Emit assay's linear range of up to 6.50 g/L ethanol was a major advantage over the ADx and aca assays; these assays were only linear to 3.00 g/L. PMID- 1293404 TI - Morphine determination by gas chromatography/mass spectroscopy in human vitreous humor and comparison with radioimmunoassay. AB - A gas chromatographic-mass spectroscopic method (GC/MS) for morphine determination in human vitreous humor was developed. Reversed-phase solid-liquid extraction gave better sample purification compared with liquid-liquid or normal phase solid-liquid extractions. In 10 real cases of death by heroin overdose, the correlation between the results obtained by GC/MS and by radioimmunoassay (RIA) was studied. PMID- 1293405 TI - Application of gas chromatographic determination of organotin compounds to basic research on the metabolism of triphenyltin chloride in rats. AB - This paper describes the application of gas chromatographic determination of organotin compounds to basic research on the metabolism of triphenyltin chloride in rats. Phenyltin compounds were extracted (as chloride) from rat-liver homogenates and subcellular fractions with hydrochloric acid and n-hexane-benzene (3:2, containing 0.05% tropolone). These organotin compounds were pentylated with a Grignard reagent prior to capillary gas chromatography. The absolute detection limits were in the range of 3.6 to 4.4 pg as tin. The absolute recoveries of phenyltin compounds added to homogenized whole liver and each subcellular fraction sample ranged from 73.9 to 97.4%. The intracellular distribution of triphenyltin and its metabolites in the liver was observed for 72 h after a single oral dose of triphenyltin chloride was given to rats. The tri-, di-, and monophenyltin compounds in the fractions reached maximal amounts about 6, 48, and 72 h after administration, respectively. Also, the concentrations of monophenyltin compounds in the liver were typically lower than to those of di- and triphenyltin compounds. The highest contents of di- and triphenyltin compounds per protein were found in the microsomal fractions. PMID- 1293406 TI - Modification of Emit assay reagents for improved sensitivity and cost effectiveness in the analysis of hemolyzed whole blood. AB - This report describes an improved method for the direct detection of a broad spectrum of drugs of abuse in hemolyzed whole blood by means of Syva Emit enzyme immunoassay. Improvements include a 1.5 to 10 fold increase in Emit assay sensitivity along with a 2 to 4 times increase in the normal number of assays per kit. This was accomplished by enzyme substrate and cofactor supplementation with a commercially available product (Raichem), assay reagent dilution, and extension of the absorbance measure time. The Emit drug abuse in urine (d.a.u.) assays used in this study included amphetamine, barbiturate, methadone, methaqualone, opiate, benzodiazepine metabolite, phencyclidine, and propoxyphene. The Emit serum assays used were the benzodiazepine and the tricyclic antidepressant assays. The within run coefficients of variation ranged from 0.25 to 0.66%, and the between-run coefficients of variation ranged from 0.45 to 1.00%. The proposed method allows for the analysis of hemolyzed whole blood using both Emit d.a.u. and serum assays. It is sensitive and can detect therapeutic or subtherapeutic concentrations of drugs in all assays tested. The method is simple, rapid, and allows for the direct analysis of a methanolic extract of whole blood without lengthy sample concentration steps. The method allows for the detection of highly potent drugs and for long-term monitoring of drug metabolites and conjugates. This could be beneficial for therapeutic drug monitoring, assessing patient compliance, and detection of previous drug use. PMID- 1293407 TI - Serial capillary gas chromatography/Fourier transform infrared spectrometry/mass spectrometry (GC/IR/MS): qualitative and quantitative analysis of amphetamine, methamphetamine, and related analogues in human urine. AB - A method using serial capillary gas chromatography/Fourier transform infrared spectroscopy/mass spectrometry (GC/IR/MS) for the analysis of derivatized amphetamine, methamphetamine, and related analogues was developed. The GC/IR/MS was configured and optimized with a Hewlett-Packard (HP) 5890A gas chromatograph with a 12-m x 0.32-mm i.d. HP-5 capillary column serially interfaced through an HP 5965A infrared detector to an HP 5970 mass selective detector with a fused silica 1.2-m x 0.10-mm i.d. column. Urine samples are extracted and derivatized as heptafluorobutyryl (HFBA) derivatives. For quantitation GC/MS in the selected ion monitoring (SIM) mode was used, with D,L-amphetamine-D5 as the internal standard. Gas chromatography/Fourier transform infrared spectrometry (GC/FT-IR) quantitation uses a selected wavelength chromatogram, spectral subtraction, double internal standard method using both D,L-amphetamine-D5 and 4-phenyl butylamine. Sensitivity for the combined GC/MS and GC/FT-IR system for amphetamine and methamphetamine shows limits of linearity of 100 to 5000 ng/mL, a limit of detection of 25 ng/mL, and a limit of quantitation of 98 ng/mL. The overall recovery for amphetamine and related analogues was greater than 85%. Precision studies for concentrations over the range of 200 to 1500 ng/mL showed coefficients of variations ranging from 2.8 to 13.0%. Correlation studies for quantitative GC/MS SIM and GC/FT-IR are greater than 0.98 for amphetamine, methamphetamine, and related analogues. Each analysis includes GC/MS SIM and GC/FT-IR quantitation, qualitative nonselective full spectra GC/FT-IR, and GC/MS scans of HFBA derivatives cross-referenced with an internal drug library, which provides high confidence and a means for the surveillance of amphetamine-like chemical analogues. PMID- 1293409 TI - Concerning norcocaine, ethylbenzoylecgonine, and the identification of cocaine use in human hair. PMID- 1293408 TI - Toxicological findings in a fatal case of acebutolol self-poisoning. AB - A fatal case of acebutolol self-poisoning is presented. After single-step liquid liquid alkaline extraction, acebutolol was identified by using an HPLC/DAD screening procedure. By means of a specific HPLC method, acebutolol was then quantified in a large range of postmortem samples. The blood acebutolol concentration was 34.7 micrograms/mL. The tissue distribution of the drug is discussed in the light of the existing literature. PMID- 1293410 TI - A biological monitoring method for cadmium. PMID- 1293411 TI - How specific for ethanol is breath-alcohol analysis based on absorption of IR radiation at 9.5 microns? PMID- 1293412 TI - Coping strategies among police recruits in a high-stress training environment. AB - The use and impact of coping strategies were explored in a setting of environmental stress. The sample consisted of 180 police recruits subjected to training stress in a U.S. police academy. Measures of coping, personal distress, and life stressors were used. Recruits who scored high on personal distress tended to use more coping strategies than those who had lower distress scores. These findings suggest that the magnitude of personal distress may be an important factor in determining which array of coping techniques is used. In terms of effectiveness, the coping strategies of distancing and planful problem solving significantly reduced distress. Escape/avoidance and self-control coping did not appear to work in the police situation and significantly increased distress. PMID- 1293413 TI - Ethnic group preferences and the evaluation of ethnic identity among adolescents in The Netherlands. AB - The relationship between the evaluation of ethnic identity and ethnic group preferences among Dutch and that among ethnic minority adolescents was examined. It was predicted that a more positive attitude toward one's own ethnic identity would be associated with a higher level of ingroup preference. This prediction was confirmed, and this led to the question of how inter-ethnic relations and a positive ethnic identity could be stimulated simultaneously. Not only the ingroup aspect of ethnic group relations was studied but also the outgroup aspect. As members of the high-status group, the Dutch subjects showed a higher level of ingroup preference, compared with ethnic minorities. Also, own-group identification and own-group-oriented patterns of preferences among the Dutch subjects were found to be accompanied by the rejection of minority groups. No such tendency was found among adolescents from ethnic minorities. PMID- 1293414 TI - Facts and myths of suicide in Canada and the United States. PMID- 1293415 TI - Investigation of circadian rhythms in anaerobic power and capacity of the legs. AB - Previous work has demonstrated that exercise performance varies with time of day. The aim of this study was to investigate the influence of time of day on measures of anaerobic power and anaerobic capacity. Twelve male subjects, aged 18-22 years, performed a stair run test, a standing broad jump and the Wingate Anaerobic Test on twelve separate occasions. These were at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours, duplicate measurements being obtained at each time point. Subjects' diet and activity prior to exercise and the laboratory temperature were controlled. Pre-exercise rectal temperature was measured on each occasion. The rectal temperature data conformed to a cosine function: its peak occurred at 18:11 hours and the peak to trough variation was 0.76 degrees C (p < 0.001). There was a rhythm in performance on the stair run and the broad jump tests, in phase with the curve in rectal temperature. Results for peak power and mean power production on the Wingate test did not display a significant circadian rhythm. The stair run and broad jump tests seem to be more sensitive to circadian rhythmicity than does the Wingate Anaerobic Test. PMID- 1293416 TI - Effect of time of day on adaptive response to a 4-week aerobic exercise program. AB - The circadian effects of an aerobic training program were studied in 3 groups of men who exercised at different times of day. Twelve healthy sedentary men were assigned to morning (9:00-9:30), afternoon (15:00-15:30) or evening (20:00-20:30) exercise groups. Each group performed a 30-minute 60% VO2max cycle ergometer exercise 4 days per week over a 4-week period. Maximal oxygen uptake (VO2max) was estimated and adaptive responses of heart rate and blood lactate levels to the training program were measured. After 4 weeks, the afternoon group showed a significant increase in estimated VO2max. A significant decrease in heart rate and blood lactate responses occurred in the afternoon and morning groups and the afternoon and evening groups, respectively. These results suggest that aerobic training is most effective in the afternoon. PMID- 1293417 TI - Isometric and isokinetic knee joint performance in Japanese alpine ski racers. AB - Isometric and isokinetic (concentric and eccentric, strength of alpine skiers with different performance levels were measured. Nine national (elite, EG) and 10 collegiate (trained, TG) female alpine skiers (16 to 23 years of age) performed maximal voluntary knee extension and flexion. Peak torque was measured at an angular velocity of 30 deg.s-1. The cross-sectional area (CSA) of thigh muscles (quadriceps and hamstring muscles) was determined by an ultrasonic method. No significant differences in anthropometric variables and CSA were observed between EG and TG. EG had significantly greater (p < 0.01 for extensors and p < 0.05 for flexors) eccentric knee extensor and flexor strength than that of TG whereas no significant differences were noted in isometric and concentric strength. Eccentric strength/CSA ratio was also higher for EG than for TG. It was suggested that knee extension and flexion strength during eccentric muscle action might be related to the performance level of alpine skiers. PMID- 1293418 TI - Force and power of preferred and non-preferred leg in young soccer players. AB - The purpose of this study was to assess the effects of soccer training on strength and power of leg extensor muscles in preadolescent boys and their possible influence in developing a muscular lateral dominance. Twenty male children (mean age 9.6 yr), ten soccer players and ten untrained subjects, participated in this study. Force and power were measured at five constant cranking velocities on an isokinetic bicycle dinamometer. Each isokinetic load was given after each trial. Force and power outputs were calculated for each limb. Soccer players always showed higher and statistically significant differences (p < 0.05) for force and power values for all considered pedal frequencies. No significant differences were observed for force and power values between preferred and non preferred limb. The results demonstrate the effect of soccer training on the increase of force and power of both legs regardless of lateral dominance. PMID- 1293419 TI - The relative contribution of strength and physique to running and jumping performance of boys 7-11. AB - The purpose of this study was to determine the association of static strength with motor performance of 7 through 11 year old boys (N = 60) after accounting for differences in physique, i.e., body size, shape, and composition. Static strength measures included thigh extension, leg extension and plantar flexion measured by electronic transducer and back lift, leg lift, and right and left grips measured by spring dynamometer. Measures of body composition consisted of fat estimated from triceps, subscapsular and calf skinfolds, and fat-free body weight estimated from potassium-40 measurements. Body structure consisted of skeletal widths, and segment girths, lengths and volumes. The dependent variables were vertical jump, standing broad jump, 50-yard dash, 600-yard run and mile run. The measures of strength increased the variance accounted for from 10 to 23% over that when body size, composition and structure were used without strength. An exception was vertical jump where no increase in the variance accounted for was found with the addition of strength variables. The regression equations determined for the sample of 60 boys rendered multiple R's ranging from 0.64 (mile run) to 0.75 (50-yard dash). It was concluded that strength has a significant relation to motor performance and that its contribution can be better assessed after accounting for differences in body size, shape, and composition. PMID- 1293420 TI - The heart rate VO2 relationship of aerobic dance: a comparison of target heart rate methods. AB - The purpose of this study was to examine the relationship between heart rate (HR) and oxygen consumption (VO2) for aerobic dance exercise. Therefore, eleven females completed 20 minutes of aerobic dance with continuous monitoring of HR and VO2. These physiological responses were analyzed with correlation/regression techniques. The results showed that for aerobic dance to produce a response in excess of 50% of VO2 max, the target HR must be approximately 80% of the age predicted HR max or greater. In contrast, previously reported data for treadmill running shows that 50% of VO2 max is achieved at approximately 65% of age predicted HR max in females. The maximum heart rate reserve (Karvonen) method was also found to underestimate the actual VO2 of AD. With the Karvonen method, the target heart rate must approximate 65% of maximum HR reserve in order to elicit a VO2 response which is representative of 50% of VO2 max. These data support recent research which illustrates that target heart rate prescriptions derived from treadmill testing may fail to accurately place AD participants in the recommended training zone. PMID- 1293421 TI - Factors enhancing cardiac output in resting subjects during cold exposure in air environment. AB - Six young males, in semi-nude conditions, resting in dorsal reclining position, were exposed successively to a thermoneutral environment (30 min), a cold environment (1 degree C) (Cold) or thermoneutrality (Control) (120 min), and during 60 min recovery in thermoneutral conditions. Cardiac output has been measured using a Dual Beam Doppler. During cold stress a significant increase of heart rate (66.4 +/- 6.4 to 91.0 +/- 14.9 beats.min-1), systolic blood pressure (119.5 +/- 7.8 to 218.7 +/- 18.7 mmHg), diastolic blood pressure (68.1 +/- 11.7 to 114.3 +/- 28.3 mmHg) and cardiac output (5.42 +/- 0.96 to 8.08 +/- 1.28 l.min 1) were observed. On the contrary initial systolic aorta flow acceleration is significantly lowered (1130 +/- 120 to 840 +/- 170 cm.s-2). Systolic ejection volume remained unchanged throughout the whole experiment. Increase in cardiac output during cold air (1 degree C) exposure is thus only imputed to the higher heart rate partly due to hypersecretion of catecholamines. The diminution of the blood flow acceleration could be related to a lesser arterial compliance and/or to the cold induced hemoconcentration. Enhanced heart's mechanical work due to sympathetic stimulation, seems thus to be absorbed by the increase in the peripheral resistance. PMID- 1293422 TI - Body composition of university students by hydrostatic weighing and skinfold measurement. AB - The body composition of 124 male and 70 female Tartu University students was measured by three different methods: hydrostatic weighing by maximal expiration, hydrostatic weighing by maximal inspiration and subcutaneous fat thickness measurements. Our results show that the proposed body density measuring method by maximal expiration is simple, reliable and applicable not only in indoor swimming pools but in field conditions as well. The second new hydrostatic weighing apparatus is more comfortable for the subjects where the body density is measured at maximal inspiration. The mean body density of males was somewhat higher when measured by the maximal inspiration (1.066 +/- 0.012 g.ml-1) than when measured by the maximal expiration (1.063 +/- 0.009 g.ml-1, p < 0.05). For females, on the contrary, the maximal expiration method (1.044 +/- 0.010 g.ml-1) yielded a higher body density value than when measured by the maximal inspiration (1.040 +/- 0.011 g.ml-1, p > 0.05). The body fat percentage measured by skinfold thickness correlated significantly with the body fat percentage calculated by body density by maximal expiration (males r = 0.420, females r = 0.531) and inspiration (males r = 0.507, females r = 0.663). We must conclude that the presented two methods of measuring body density offer new possibilities for densitometric analysis without the need for expensive laboratory equipment. PMID- 1293423 TI - Effect of middle-intensity exercise on carnitine and beta-hydroxybutyrate plasmatic concentration in men and women. AB - The purpose of this study is to describe the dynamics of carnitine, its esters and beta-hydroxybutyrate, during a prolonged moderate-intensity physical exercise, as the literature data (Angelini 1986, Carlin 1986, Lennon 1984) up to date reported were not uniform. In our study twenty-two untrained subjects (11 males, 11 females) performed a test exercise on a motor-driven treadmill for 90 min at 50-60% of VO2 max. Blood samples were obtained at rest, at 20, 40, 60 and 90 min during the exercise and after 30 min of recovery. Men show an increase over rest values in short chain acyl carnitine after 90 min of exercise higher than women (M 157%, F 80%), while women have a more elevated relative increase in beta-hydroxybutyrate (M 201%, F 233%); Total carnitine in both sexes is not significantly modified. PMID- 1293424 TI - Little effect of long-term, self-monitored exercise on serum lipid levels in middle-aged women. AB - To study the effect of long-term, self-monitored exercise on physical fitness and serum lipid levels of middle-aged, nonsmoking females, a controlled study was conducted in 33 sedentary Swiss women. Seventeen women were randomly allocated to jog 2h/wk for 4 months on an individually prescribed and heart rate controlled base, whereas 16 women served as controls. Although leisure-time physical activity increased significantly in exercisers compared to controls, the average running distance of 10.9 km/wk was somewhat less than expected. The "net decrease" (4-month change in exercisers minus 4-month change in controls) in the sum of four skin-folds was -4.85 mm (p < 0.05). Four-month changes in serum lipids were generally small and nonsignificant. For example, the net decrease in total triglycerides was -0.2 mmol/l (p = 0.13). Correlational analyses revealed significant associations between changes in the waist-hip ratio and changes in total cholesterol (total-C) or the HDL/total-C ratio (r = 0.44, p < 0.01 and r = 0.29, p < 0.05, respectively). An increase in endurance capacity was associated with an increase in the HDL2-subfraction and in the ratio of HDL/total-C (r = 0.46, p < 0.05 and r = 0.52, p < 0.01). Multivariate linear regression analyses confirmed a change in endurance capacity as the statistically strongest positive predictor of changes in HDL, HDL2 and the HDL/total-C ratio. However, women who used oral contraceptives did not show any favourable lipid changes despite a considerable improvement in endurance capacity. The present training study in healthy, habitually sedentary middle-aged women was not able to show the same beneficial changes in serum HDL concentration as seen in male counterparts, when analyzed according to the principle of intention-to-treat. Exploratory analyses revealed that a too low jogging activity as well as a confounding effect of oral contraceptive use may partially account for the lack of significant changes in serum lipid levels after training. PMID- 1293425 TI - The effect of exhaustive exercise on salivary immunoglobulin A. AB - The purpose of this study was to examine salivary immunoglobulin A (s-IgA) responses to exhaustive exercise. Twenty-nine, college age (means +/- SD = 21.45 +/- 3.1 yrs; range 18-29 yrs) moderately active males (running < 10 miles per week) performed an incremental treadmill test to exhaustion. Unstimulated salivary samples, collected before as well as immediately and one hour following the test, were analyzed for s-IgA using an enzyme-linked immunosorbent assay (ELISA). Mean s-IgA levels decreased significantly (24.4%, p < 0.05) immediately following the maximal test, and remained depressed (16.9%) one hour after the test. Of the 29 subjects, five exhibited an increase (range = 1.3 to 53.3%) in s IgA following the exercise bout. The results of this study suggest that exhaustive exercise may temporarily reduce salivary IgA levels. PMID- 1293426 TI - Strengthening physical self-perceptions through exercise. AB - Two studies examined the effects of physical activity/exercise on physical self perceptions, self-efficacy, body satisfaction, fitness and relationships among these variables. In study 1, 34 female undergraduates participated in a 10-week exercise/activity program. Participants were selected from existing classes forming a weight training, aerobic exercise and activity control group. Results revealed changes in physical self-perceptions, strength, and body composition over the 10-weeks. Improvements in physical self-perceptions and fitness occurred independent of exercise/activity group. Groups differed in the perceived importance attached to physical self-perceptions. Correlations among the measures revealed relationships among physical self-perceptions, body satisfaction, global self-esteem, and fitness. In study 2, we hypothesized that weight training would have a greater effect on physical self-perceptions and body image perceptions than physical education activity classes. Thirty-seven males and 28 females were selected from existing classes forming a weight training and activity group. Results revealed no significant changes in physical self-perceptions, body image, or global self-esteem over the 10-week program, while strength and physical self efficacy improved. Correlations among measures from both studies offer preliminary support for Sonstroem and Morgan's model for the examination of self esteem in exercise settings. PMID- 1293428 TI - The fates of Czechoslovak contestants in Olympic games. AB - Since the Second Olympic Games of the new era up to the Games in 1988 on the whole 2031 Czechoslovak competitors participated in both Summer and Winter Games. The author succeeded in compiling items on the length of life and causes of decease of 265 Olympic participants who died up to the end of 1989. The study of those items revealed that the length of living of those athletes who died in the period 1950 till 1989 was 67.4 years. That indice may be compared with men in population with a mean length of life 67.7 years in 1988. It is however necessary to take into consideration that the studied sample of Olympic competitors represents a certain selection of men. The causes of natural death of Olympic competitors do not differ in principle from natural deceases of other former Czechoslovak athletes and also no expressive differences were found in comparison with natural causes of death of men in population. PMID- 1293427 TI - Effect of training on the reaction time of Indian female hockey players. PMID- 1293429 TI - Lymph, lymph glands, and homeostasis. AB - Under aerobic conditions every respiring cell in the human body normally consumes oxygen to burn food and produce stoichiometric quantities of water which dissolves carbon dioxide and less soluble cell products. The effluent water and solutes appear in the form of lymph in the interstices between cells. The lymph effluent from all respiring cells flows to become the circulating lymph and blood plasma which coordinately sustain a steady state of homeostasis throughout the internal milieu. As a result, every living cell served by the vascular system has equal opportunity to partake of water and solutes emanating from or absorbed by remaining cells. Solute quantities available depend on cell location, regional plasma flow, local vascular permeability, molecular size, configuration, solubility and concentration, as well as avid cell receptors. Proportional to oxygen consumption, organized lymph glands develop in environments of relatively high oxygen tension around regional arteries to filter and process lymph coming from regional cells, and to produce effluent lymph rich in soluble globulins extruded by local mononuclear cells (especially macrophages, plasmacytes, lymphocytes), along with suspended small cytoplasm-poor lymphocytes. In turn, such dissolved globulins and remarkably motile small lymphocytes help feed, regulate growth and provide immunity to remaining cells. The lymph effluent from lymph glands and residua from capillary filtrates, along with newly absorbed solvent water, join the blood circulation during pulmonary inspiration in volumes proportional to the volume of air inspired with each breath. PMID- 1293430 TI - Use of tonometry to assess lower extremity lymphedema. AB - Tissue tonometry was used to assess the outcome of microwave hyperthermia in treatment of 9 patients with lower extremity lymphedema. After microwave treatment, tissue tonicity of the lymphedematous leg returned toward normal. This improvement correlated with a reduction of leg volume and circumference, decrease in "inflammation" in the edematous subcutaneous tissue and clinical episodes of cellulitis. Possible factors involved in this shift in tissue tonicity toward normal include mobilization of excess fluid and plasma proteins from the interstitium, reduction in microvascular cellular infiltrate and changes in the elastic and viscoelastic properties of matrix collagen, elastin and ground substance following hyperthermia. PMID- 1293431 TI - A comparative study of acetylcholinesterase activity in bovine (S. cervi) and human (B. malayi, W. bancrofti) filaria. AB - Setaria cervi, a bovine filarial parasite, contains a significant amount of acetylcholinesterase (AChE) activity with microfilaria having five to ten times more AChE activity than female and male adult worms, respectively. Because AChE shows substrate specificity and hydrolyzes acetylthiocholine but not butrylthiocholine, this parasitic enzyme is likely a true acetylcholinesterase. The latter also resembles an AChE enzyme in the human filarial parasite B. malayi which hydrolyzes acetylthiocholine iodide three times faster than butrylthiocholine iodide. The S. cervi AChE, like its counterpart, also exhibit inhibition with eserine, a specific inhibitor of this enzyme. Subcellular localization of AChE in adult female worms shows enzyme activity both in the mitochondrial and post-mitochondrial fraction. However, enzyme activity in the soluble fraction is twenty-seven times greater than in the mitochondrial fraction. PMID- 1293432 TI - Dermal lymphatics in myotonic dystrophy. AB - Myotonic dystrophy is an hereditary disorder of several organ systems. Skeletal muscle is a principal target organ, but abnormalities also occur in the peripheral microcirculation. Because morphological and functional changes in the dermal blood microcirculation may affect interstitial fluid drainage of the skin, we examined dermal lymphatic morphology in adult patients with myotonic dystrophy. Skin biopsies were taken from the big toe from patients with myotonic dystrophy (age 18-50 years) and subjected to light and electron microscopy; five healthy subjects served as controls. The salient findings in myotonic dystrophy were ultrastructural changes of the lymphatic endothelial cells and the fibrillar elements that surround the lymphatic wall. These abnormal lymphatic findings are interpreted in light of changes in the blood microvasculature and loose connective tissue in this disorder. PMID- 1293433 TI - New technique for the subcutaneous drainage of peripheral lymphedema. PMID- 1293434 TI - Enzyme-histochemical identification of the human lymphatic capillary by adenylate cyclase. AB - This investigation was performed in order to establish a new histochemical method for the identification of lymphatic capillaries. The microvasculature in specimens from human foreskin was examined for adenylate cyclase and alkaline phosphatase activity by light and electron microscopy. Lymphatic capillaries showed positive adenylate cyclase reactivity and negative alkaline phosphatase reactivity whereas the blood capillaries showed a positive reaction for alkaline phosphatase and a negative one for adenylate cyclase. The presence of adenylate cyclase activity in the endothelium of the lymphatic capillary may relate to microvascular function including the transcapillary exchange of water and solutes. PMID- 1293435 TI - Review of neural network applications in medical imaging and signal processing. AB - The current applications of neural networks to in vivo medical imaging and signal processing are reviewed. As is evident from the literature neural networks have already been used for a wide variety of tasks within medicine. As this trend is expected to continue this review contains a description of recent studies to provide an appreciation of the problems associated with implementing neural networks for medical imaging and signal processing. PMID- 1293436 TI - Fundamental characteristics of human limb electrical impedance for biodynamic analysis. AB - The paper describes the use of human-limb impedance for biodynamic analysis. The change of human-limb impedance during movement was measured, and was found to be related to kinematic and kinetic parameters. Strong relationships were found between the velocity of change of the forearm impedance and the angular velocity of the elbow joint (correlation coefficient r = -0.97), between the the change of forearm impedance and the velocity of a human limb (r = 0.79). A change of upper limb impedance was caused by a change in a sectional area of muscular tissue in the measured part and a change of blood volume during movement of an upper limb. In tennis, there was a strong relationship between a change of forearm impedance and ball velocity (r = 0.87). Impedance waveforms were useful for analysis of the movement pattern and the stability of movement in tennis. This method has the following characteristics: (a) it does not have a spatial and temporal limitation for measurement; (b) the subject is scarcely restricted in movement; (c) the data processing can be handled easily and quickly; (d) impedance waveforms inherently show magnitude, form and stability of movement. PMID- 1293437 TI - Simulation method for cardiac stroke volume estimation by intracardiac electrical impedance measurement. AB - Using the electrical impedance measurement technique to investigate stroke volume estimation, three models of the ventricle were simulated. A four-electrode impedance catheter was used; two electrodes to set up an electric field in the model and the other two to measure the potential difference. A new approach, itself an application of the quasi-static case of a method used to solve electromagnetic field problems, was used to solve the electric field in the model. The behaviour of the estimation is examined with respect to the electrode configuration on the catheter and to catheter location with respect to the ventricle walls. Cardiac stroke volume estimation was found to be robust to catheter location generating a 10 per cent error for an offset of 40 per cent of the catheter from the chamber axis and rotation of 20 degrees with respect to the axis. The electrode configuration has a dominant effect on the sensitivity and accuracy of the estimation. Certain configurations gave high accuracy, whereas in others high sensitivity was found with lower accuracy. This led to the conclusion that the electrode configuration should be carefully chosen according to the desired criteria. PMID- 1293438 TI - Cellular automation model of ventricular conduction. AB - A computer simulation of ventricular conduction is presented with a discrete element ventricular conduction model. The model is shown to be capable of demonstrating normal ventricular rhythm, including QRS and T-waves, plus a variety of rhythm disturbances including missed beats, electrical alternans and self-sustaining instability with arrhythmias. The morphology of the range of alternans produced bears a strong resemblance to certain clinically recognised arrhythmias. PMID- 1293439 TI - Pupillometer for clinical applications using dual 256-element linear CCD arrays. AB - A new pupillometer for measuring the size of the pupil of the human eye is described. It uses two inexpensive 256-element charge coupled device (CCD) arrays in an orthogonal configuration. The system is controlled and data are analysed by means of a Z80A microcomputer. Software allows the position and diameter of the pupil to be displayed on a monochrome video monitor. Infra-red diodes irradiate the eye so that measurements can be made in darkness. The accuracy is better than +/- 0.1 mm, over the range 3.2-9.5 mm. Dynamic measurements of the pupil light reflex response can be made with sampling periods as short as 20 ms. PMID- 1293440 TI - Effect of mains interference on time coherent averaging. AB - The paper deals with the influence of mains interference on time coherent averaging using an internal trigger. The general distribution of the time jitter is derived and applied to a simplified signal. The authors prove that no amount of averaging can do away with this type of interference. Finally, the deformation this type of jitter has on a step signal is computed. PMID- 1293441 TI - Optimal time-window duration for computing time/frequency representations of normal phonocardiograms in dogs. AB - The optimal duration of the time-window used to compute the time-frequency representation (spectrogram) of the phonocardiogram was studied in four dogs by using intracardiac and thoracic measurements of the PCG. The power and cross spectrograms of the intracardiac and thoracic PCGs were computed using a fast Fourier transform algorithm and a sine-cosine window with 10 per cent decaying functions. A coherence spectrogram was also computed for each dog to study the linear relationship between the two signals and determine the optimal time-window duration. Results show that the optimal range of the time-window duration is between 16 and 32 ms. A time-window shorter than 16 ms spreads out low-frequency components into the higher frequencies and generates a spectrographic representation with poor frequency resolution (> or = 62.5 Hz). A window larger than 32 ms increases the frequency resolution but smears the spectrographic representation of the signal in the time domain and thus cannot correctly reflect the time-varying properties of the signal. In both cases, the amplitude of the coherence function computed between the left ventricular and the thoracic phonocardiograms is overestimated. PMID- 1293442 TI - New method of automated sleep quantification. AB - Since its discovery some 50 years ago, the electro-encephalogram (EEG) has formed the basis for classification of sleep into several stages, either laboriously performed by visual examination of the EEG and related signals or, more recently, by automated techniques. Both visual scoring and most automated analyses are highly subjective and rely on application of a predefined set of rules. A method of analysing the EEG which requires no such application of rules and aims to give some indication of the dynamics of sleep in humans is proposed in the paper. PMID- 1293443 TI - Impedance plethysmography for blood flow measurements in human limbs. Part 2. Influence of limb cross-sectional area. AB - The cross-sectional area of a limb varies along the extremity. This is of great importance when impedance plethysmography is used for limb blood flow studies. The actual measurement site, as well as the interelectrode distance, must be carefully selected to avoid underestimation of the blood flow value. The distance between the potential electrodes should be less than 10 cm for an adult subject. PMID- 1293444 TI - Mathematical model for the exchange of gases in the lungs with special reference to carbon monoxide. AB - A mathematical model has been formulated for the simultaneous exchange of gases O2, CO2, CO and N2 in the lungs. The model takes into account the physiological parameters, such as ventilation rate, diffusing capacity of the lungs, cardiac output, total volume of blood in the body and the interaction of gases in the blood. The nonlinear functions for representing O2, CO2 and CO dissociation curves have been used. The results predicted from the model are in good agreement with those based on the ventilation/perfusion relationships. The COHb build-up in the blood, computed from the model as a function of exposure time, is in good agreement with the experimental values. The consideration of capillary blood pO2 as a constant value, instead of an independent variable, is shown to introduce a maximum error of 0.25 per cent in the blood COHb. The model is applied to analyse the COHb levels at high altitude. PMID- 1293446 TI - Faradic resistance of the electrode/electrolyte interface. AB - A new method is used to measure the direct-current (Faradic) resistance of a single electrode/electrolyte interface. The method employs a constant-current pulse and a potential-sensing electrode. By choosing a sufficiently long pulse duration, the voltage between the test and potential-sensing electrode exhibits a three-phase response. In the steady-state phase, the voltage measured is equal to the current flowing through the electrode Faradic resistance and the resistance of the electrolyte between the test and potential-sensing electrode. By measuring this latter resistance with a high-frequency sinusoidal alternating current, the voltage drop in the electrolyte is calculated and subtracted from the voltage measured between the test and potential-sensing electrode, thereby allowing calculation of the Faradic resistance. By plotting the reciprocal of the Faradic resistance against current density and fitting the data points to a third-order polynomial, it is possible to determine the zero-current density (Faradic) resistance. This technique was used to determine the Faradic resistance of electrodes (0.1 cm2) of stainless-steel, platinum, platinum-iridium and rhodium in 0.9 per cent NaCl at 25 degrees. The zero current Faradic resistance is lowest for platinum (30.3 k omega), slightly higher for platinum-iridium (47.6k omega), much higher for rhodium (111k omega) and highest for type 316 stainless-steel (345k omega). In all cases, the Faradic resistance decreases dramatically with increasing current density. PMID- 1293445 TI - Monitoring of respiratory and heart rates using a fibre-optic sensor. AB - A new method, which uses a fibre-optic probe to monitor respiratory and heart rates simultaneously, has been developed and evaluated. The results provide evidence that it is possible to monitor respiratory and heart rates using the reflection mode of photoplethysmography (PPG). The fibre-optic probe makes it possible to monitor from different sites on the patient, and the method is convenient to use. In addition, the probe is X-ray transparent, insensitive to electromagnetic interference (e.g. during MRI investigation) and may be made very light and small. Therefore the method is suitable for the observation of both adults and neonates, in hospitals as well as in other environments. PMID- 1293447 TI - Numerical model of blood flow through a bifurcation: interaction between an artery and a small prosthesis. PMID- 1293448 TI - Filtering respiration and low-frequency movement artefacts from the cardiogenic electrical impedance signal. PMID- 1293449 TI - Instrument for controlling drowsiness using galvanic skin reflex. PMID- 1293450 TI - Effect of milk on myoelectrical activity of the stomach--an electrogastrographic study. PMID- 1293451 TI - Photoplethysmograph from a laser source. PMID- 1293452 TI - Teachers at a British medical school. AB - Clinical teachers' attributes, beliefs and attitudes to teaching were measured by mailing a questionnaire to a 50% sample of staff at a British medical school. This paper describes the attributes of the 80% who responded. The majority (83%) were male and females were particularly under-represented in the upper echelons of academia. Most (57%) taught at least once weekly, though 20% taught less often than once a month. The 41% who were primarily NHS employees were as active in teaching as those employed by the University. Small group teaching was most frequently undertaken by 73%, though 17% (who were more likely to be University employees) most often lectured. Only 19% of teachers had attended a course in medical education in the previous 5 years--these were more likely to have qualified relatively recently and to be University employees. Few (9%) teachers claimed membership of a medical education society. It is hoped that these findings will stimulate debate on how medical school teachers are selected, how they can be helped to improve their teaching performance and how their enthusiasm for teaching can be fostered. PMID- 1293453 TI - Ten statements on the motivation of medical teachers to teach. AB - Not only high number of students, increasing disintegration of curricula, lack of resources or hindering state regulations and laws seem to be the crucial problem in medical education worldwide but in particular substantially reduced interest and poor commitment in educational matters. Ten statements on possible reasons for the teachers' lack of motivation to teach are given and proposals for promoting their commitment are made. PMID- 1293454 TI - Bulletin boards for faculty development. AB - Within the faculty development program of a Department of Family Medicine at a major research university, bulletin boards offer an alternative method for communicating new information, reinforcing knowledge previously acquired, and stimulating faculty to think about new ideas. This paper describes a five-step strategy for integrating bulletin boards into a faculty development program. PMID- 1293455 TI - Faculty development in the health professions: conclusions and recommendations. AB - This report summarizes recent literature reviews and resource books on faculty development in the health professions and describes findings from articles not previously reviewed. Nine conclusions about faculty development in the health professions are drawn: (1) the concept of faculty development is evolving and expanding; (2) research skills are becoming a major focus of faculty development; (3) teaching skills are still a prominent aspect of faculty development; (4) fellowships are being used effectively to recruit and train new faculty; (5) the institutional environment has become a focus of faculty development; (6) faculty evaluation is an effective approach to faculty development; (7) the efficacy of faculty development needs better research documentation; (8) model curricula have been developed for different types of faculty; and (9) comprehensive faculty development centers are gaining in popularity. A set of recommendations based on the conclusions drawn is offered for those planning faculty development interventions. PMID- 1293456 TI - Faculty mentors for medical students: a critical review. AB - New concern about the psychosocial development of medical students has resulted in a call for closer relationships between faculty and medical students. This review examines the literature on advising programs in medical schools and on mentoring generally to develop a better understanding of how faculty and students might interact. Innovative advising programs are discussed within the context of current thought about the value and structure of mentoring relationships. PMID- 1293457 TI - Changes in personal health behaviors of medical students. AB - Physicians, including medical students, seem to lead healthier lives than the general public. Whether their favorable health behavior is learned through medical education is not known. This study uses a standardized health risk assessment to compare the personal health behaviors of a single class of medical students before and after completing their clinical rotations. Our findings confirm that medical students exhibit healthier lifestyle behaviors than that of the general population, and that changes in health behaviors may evolve with training. PMID- 1293458 TI - Professional attitudes of doctors and medical teaching. AB - The attitude of doctors towards the profession influences to a large extent a number of aspects of clinical competence. Their attitude towards the patient is particularly important as it determines the quality of communication. There is reason to believe that a certain number of practising clinicians have not acquired the appropriate attitude to their patients and the skills in communicating that this entails in spite of specific undergraduate education programmes. This would warrant more and different attention to this subject by medical schools than is actually the case. The recently introduced scale of attitudes between doctor-centred, disease-oriented and patient-centred, problem oriented could provide a basis for studying, teaching and evaluating individual attitudes of students. PMID- 1293459 TI - Time involvement in journal reading and a suggested facilitation. AB - In the field of continuing postgraduate education, the reading of professional journals is an accepted method of keeping informed in regard to new developments and contemporary thought on different philosophies of treatment. Not only is such reading realized as being an efficient educational vehicle, but there is now a growing awareness of the actual necessity for any clinician to set aside specific time to the exercise. It is not always readily apparent, however, how great the time commitment can be, even when the reading is limited to selected articles. This paper sets out to indicate in quantitative terms the time that could be expected to be utilized by both general dental practitioners and academic teachers if a thorough and conscientious perusal of the journals were to be undertaken. A practical strategy for facilitating at least part of the problem is put forward in the hope of reaching a helpful compromise. PMID- 1293460 TI - A tutorial/essay project to expand the learning experience in undergraduate medical pharmacology. AB - To lessen fact overload and to enhance the teaching of pharmacologic principles in an undergraduate course we introduced a tutorial/essay project into our traditional lecture-based course. Under the guidance of a faculty tutor, each student researched an assigned topic, developed a paper incorporating the results of the literature review and his or her own attitudes and formally discussed and answered questions on the topic with the tutor. Students and tutors were enthusiastic about this learning experience especially in that it required independent student-centred activity, provided opportunity for useful student/tutor interaction and helped students to learn to integrate scientific information with their own thoughts and ideas. PMID- 1293461 TI - A review of the oncology curriculum at Dalhousie medical school. AB - The teaching of oncology at Dalhousie medical school is currently left to the discretion of the 30 university departments. There is no central coordination. This organization leaves no monitoring of curriculum content to see that what should be covered is indeed covered, nor does it provide teaching from the perspective of oncology rather than the perspective of the other individual disciplines. Following an inventory of the oncology curriculum and a survey of interns graduating from Dalhousie in 1991, we recognize deficiencies in the clinical portion of the curriculum that could be rectified with a small number of hours designed to teach the various aspects of the management of cancer patients in case-scenario, student participation sessions. PMID- 1293462 TI - Student assessment of clinical experience in general surgery. AB - Forty-two students kept a log diary of all activities during their general surgical firms at a main university hospital in London. The students saw on average 35 patients per week on whom physical aspects were discussed by the consultant with the student after the consultation in 58%, psychological aspects in 4% and social aspects in 1.6%. Students spent an average of 11.2 hours per week with patients. In outpatients students spent most of their time as passive observers, but there were opportunities for more active involvement on the wards. Here the students spent on average 1.5 hours per week personally examining patients and 1 hour per week taking histories. Each student performed on average two short and one long examination per week and 0.5 short and 2.25 long histories per week. The students received on average 2.9 hours per week of consultant teaching in small groups, junior medical staff teaching at 2.2 hours and non medical staff teaching of 1.1 hour per week. Students spent almost 4 hours per week attending formal traditional lectures in large groups. Some areas identified for improvement were: the relatively little feedback and supervision students received when personally examining patients and taking histories; the passive involvement of students in most educational settings; the small amount of time devoted to discussing social and psychologically relevant factors in the history; the few practical procedures personally performed by students; the relatively large amount of time students reported as unproductive and the small amount of time spent on self-education.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293463 TI - Establishing goals and priorities in a surgery department. AB - Limitation of resources necessitates prioritization in the planning of goals for a clinical discipline such as surgery. Private practitioners and academic surgeons have their own priorities which reflect their specific, often conflicting, interests. We describe a model (modification of Davies & Morgan, 1983) for establishing goals and priorities with input from both private practitioners and academic full-time surgeons in a large Department of Surgery. The model consists of four phases each of which is divided into input, process and output stages. During the input stage general large group discussion allows identification of disparate views. This is followed by refinement of these ideas in small group discussions (process) which results in the formulation of a report (output). Application of this model resulted in a clear definition of goals and priorities by consensus and placed education first on this list of priorities in spite of a department in which there is a predominance of private practitioners whose major area of activity is in the realm of patient care. PMID- 1293464 TI - Teaching statistics to health professionals: the legal analogy. AB - Despite the importance of statistical concepts to health professionals, the teaching of statistics to students from this field has generally been unrewarding. We feel that a few central concepts are crucial to all statistical thinking and that, for most health professionals, the communication of these is more important than learning about complex mathematical models. A device for demonstrating the parallels between a criminal legal trial and statistical hypothesis testing is presented. We feel that it can facilitate the learning of this central statistical concept. PMID- 1293465 TI - Anatomy of the upper limb: a partnership in learning and assessment. AB - Specific rehabilitation of the upper limb by the Occupational Therapist requires a sound working knowledge of the anatomy of the pectoral girdle, arm, forearm and hand. To aid the learning process the Liverpool occupational therapy students are given their assessment topics at the beginning of the course. They find a conductive partner with whom to work and practice, and together they prepare for the oral demonstration which forms the assessment test at the end of the second term. Each student completes a questionnaire at the end of the fourth term. This is designed to ascertain how confident the student felt, and how well they retain their anatomical theory of the upper limb for clinical work. PMID- 1293466 TI - A new approach in training pre-clinical medical undergraduates in community medicine in Pondicherry, South India. AB - Pre-clinical medical undergraduates are taught Community Medicine using a variety of teaching methods keeping the didactic lectures to the minimum in conformity with the latest recommendations of Medical Council of India. Five of the total twelve topics were taught using group discussion during 1988-89. The present paper gives the details of lesson plans for two topics. Evaluation was done based on the results of the written test, opinions expressed by the students and on the spot observation by the faculty members. Suggestions given by the students to improve the sessions have also been highlighted. PMID- 1293467 TI - Audit of oral examinations in psychiatry. AB - This study describes a simple set of statistical parameters for assessing the reliability and validity of oral examinations (OE). Traditional feedback to examiners tends to categorize them as 'hawks' or 'doves' on the basis of whether their personal mean mark is above or below the group mean. Our study shows that the mean OE mark on its own is not a good measure of examiner performance. We suggest that inter-rater reliability between examiner pairs is a more satisfactory indicator of reliability and face validity. The correlation between the OE marks given by an examiner and the student's subtotal from written parts of the exam (SUBTOT) is suggested as a useful indicator of OE validity. These measures, as applied to our own student exam results, suggest that our OE examiners are performing at an acceptable standard of agreement (Cohen's Kappa for pass/fail 0.74, p < 0.0001), and support the use of the OE as a method of student assessment. PMID- 1293468 TI - Do you know? An opportunity to assess how up-to-date you are with the medical education literature. PMID- 1293469 TI - [Heterogeneity of lung ventilation as an indicator of early occupational exposure effects on the respiratory system]. AB - The homogeneity of lung ventilation was evaluated in 148 male workers without any evident symptoms of impaired lung ventilation who were employed as miners (94 persons) and processors (52 persons) of PbS ore. The V2:V1 factor was calculated from the resultant of the maximum flow and volume. In the group of miners, significant increase of homogeneity was found to occur in elder workers (over 35 years of age) and in those employed for a longer period of time (above 10 years). Ventilation heterogeneity in that group was also intensified by simultaneous occurrence of chronic bronchitis. In the group of the floatation plant workers, there was a similar relationship between the ventilation heterogeneity and their age as well as employment period. As no effect of tobacco smoking on the discussed parameter was detected, it can be presumed that the effect of the working environment factors was predominant. PMID- 1293470 TI - [Neurobehavioral effects of chronic occupational exposure to mixtures of solvents used in furniture varnishing. Part I--Psychological examination]. AB - The study aimed at detecting psychological effects of chronic occupational exposure to the mixtures of solvents used in furniture varnishing. 36 exposed workers and 34 controls selected so as to account for age, education level and the nature work were examined. The following tests were used in the examinations: the Neurobehavioral Core Test Battery, Orebro Symptom Questionnaire, Perceived Stress Scale. A slow-down of perceptive and motor activities, which intensified with the duration of exposure, was the only observed adverse effect of the exposure. The workers employed for periods longer than 15 years more often reported symptoms of psychic function disturbances and deterioration of their health condition. PMID- 1293471 TI - [Neurobehavioral effects of chronic occupational exposure to mixtures of solvents used in furniture varnishing. Part II--Testing of visual evoked potentials]. AB - The study involved a group of 40 workers chronically exposed to mixtures of organic solvents. The exposure did not exceed the allowed hygienic standard. Organic changes in the central and/or peripheral nervous system were not detected. Irregular visual evoked potentials were found in 9 (22.5%) of the exposed workers. The irregularities related primarily to the latency of some components of visual evoked potentials. Those changes occurred primarily within the group of workers employed for longer periods of time (16 years and longer). PMID- 1293472 TI - [Biological evaluation of experiments in rats of Australian and Italian talc aggressiveness]. AB - In order to evaluate biological effects of Austrian and Italian talc, pulmonary and hemolytic tests as well as pathomorphological examinations were performed. 120 Wistar rats divided into 5 groups were given intratracheally 50 mg of the examined talc dust suspended in 0.5 ml of 0.9 NaCl. The control group received one 0.5 ml dose of NaCl. The observation periods were 6 and 9 months. Then the biochemical tests for hydroxyproline content in the lung were carried out along with patho-morphologic tests to evaluate the fibrogenic activity of the talcs examined. In animals the intratracheal insufflation of talc dust causes inflammatory changes within the bronchi and lungs. On the basis of biochemical examination of lung homogenates, the differences in the hydroxyproline content were determined. After 6 months the symptoms of chronic inflammation and cellular modules developed. Within another 3 months the symptoms of chronic atrophic inflammation in the bronchi were observed and cellular modules containing dust particles were detected in the lung. Hemolytic test revealed a slightly higher degree of aggressiveness of the Austrian talc. PMID- 1293473 TI - [Effect of an occupational environment containing manganese on granulocyte adherence]. AB - Workers employed in the manufacture of iron/manganese alloys were exposed primarily to manganese, but also to noise and other factors. Neutrophilic erythrocytes of those workers displayed significantly higher adherence compared to that determined in the control group. Duration of employment, occurrence of chronic bronchitis and the intensity of tobacco smoking did not affect the adhesive properties of neutrophilic granulocytes in peripheral blood. PMID- 1293474 TI - [Participation of mental workload in circulatory system reaction to occupational work]. AB - The aim of the study was to determine the degree to which the heart rate during and after work of variable physical and mental load was affected by the mental workload of moderate intensity. The subjects were 150 women aged 17-57. 24-hour recordings of their heart rates during work, leisure and sleep were taken using the Medilog recording-analysing system. Mental workload was determined in two ways: by the AET method, which enabled objective evaluation of the load, and by a method which involved subjective evaluation of work requirements and the ability to cope with them. Using the multiple regression analysis, the degree to which concurrent elements of mental and physical workload an serve as predictors of heart rate during work, leisure and sleep. The results show that physical workload is the more essential factor affecting the reaction of the circulatory system under the circumstances of concurrent mental and physical workload. By extending the measurements to involve off-duty hours, it was possible to determine that the consequences of mental workload manifested also after the work. The prolonged effect of mental workload on the heart rate was evident only when the subjective method of workload estimation was used. This points to the individual character of mental workload. The findings indicate on one hand that the share of mental workload should not be neglected during evaluation of the effects of occupational workload on the physiological reactions and, on the other, that the heart rate measurement is a useful tool for indicating essential elements of workload. PMID- 1293475 TI - [The effect of social support on women's perception of global stress and health status]. AB - Social support is considered to be an essential factor in the perception of global stress, as it reduces the impact of the stressors (and thereby protects against excessive stress), a well as reduces the detrimental effects of stress. The purpose of the study was to determine the level of social support received by women in two essential areas: family life and occupational work, and to estimate the relationships between the support level and stress perception by women and the condition of their health (estimated with the use of the Goldberg General Health Questionnaire). The APGAR questionnaire designed by G. Smilkstein was used to estimate the support. This was the first instance of the application of the method in a Polish study--with prior written consent of the author of the method. The study involved 98 women in four occupational groups (physicians, nurses, spinning machine operators, and employees of financial department of an industrial plant). The results of the study indicate that the situation of the women in respect of the received social support differs, to a statistically significant degree depending on the occupational group to which they belong. The evaluations of the support are also, significant correlated with the evaluations of global stress in the whole population test--higher results with respect to the support are correlated with the lower degree of stress. The support from the family shows higher degree of correlation with the level of the perceived stress than the support received at the place of employment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293476 TI - [Effect of combined exposure (noise, dust, nitrogen oxides) on health status of metal workers in heavy industry. Evaluation of erythrocyte metabolism]. AB - This paper presents the effects of combined exposure (noise, dust, nitrogen oxides) on the health condition of industrial workers, with special regard to red blood cell metabolism. 208 male industrial plant workers of the average age of 38.5 +/- 8.27 years and the average work period of 14.7 +/- 8.22 years were examined. The statistically significant increase of methemoglobin level was detected as well as some changes in erythrocyte metabolism in terms of increased activity of glucose-6-phosphate dehydrogenase, pyruvate kinase and in vitro production of lactic acid in erythrocytes. The observed changes indicate the influence of exposure to nitrogen oxides and the resulting cellular adaptation to unfavourable working conditions (activation of the pentose cycle and of the final stage of anaerobic glycolysis cycle). PMID- 1293477 TI - [Acetylation phenotype as a biomarker of sensitivity to the carcinogenic effect of aromatic amines]. AB - The feasibility of genetic screening used for the determination of the acetylation phenotype in workers exposed to carcinogenic aromatic amines seems to be well-grounded. A conclusion like that is supported by numerous epidemiologic observations which show that the slow acetylators are more prone to bladder cancer under the conditions of exposure to aromatic amines than the fast acetylators. The significance of the acetylation phenotype for the processes which start the transformation of the normal bladder epithelium cells into the neoplasm was explained by studying the metabolism of the carcinogenic amines in the cells of mammals, including humans. Further tests are required to explain to what degree the genetic inclination is associated with the occurrence of the slow acetylation phenotype dependent on the tobacco smoking and on other factors, such as diseases, past or present. PMID- 1293478 TI - [Carpal tunnel syndrome of occupational etiology--new problems in diagnosis and certification]. AB - The work is based on the author's own experience during her employment as an expert at the Institute of Occupational Medicine, Lodz, and on the literature on diagnosing and certification of occupational etiology of the carpal tunnel syndrome. The paper also discusses the applicability of the electrophysiological tests for occupational certification, as well as the significance of having adequate information about the workplace of the examined people and the problem of expected difficulties in evaluating exposure to the due variable structure of production and services. PMID- 1293479 TI - [Health protection in the workplace in Germany (former Federal Republic of Germany) in 1973-1990]. AB - 1. In Germany health protection against injuries at work is distinctly separated from the general health care of the population. 2. Health protection at work includes: recognition, prevention, treatment and rehabilitation connected with occupational diseases as well as prevention of accidents at work. The total cost of this system including accident indemnities is covered by the employer. 3. The system of health care and safety at work within the enterprise comprises a coordinated activity of the physician inspector and a representative of the enterprise and the owner. 4. In big enterprises there is another system operating parallel to the one mentioned above: this system provide comprehensive health care. The costs are covered by contributions both on the paid of the employers and the employees. PMID- 1293480 TI - Testicular organization and spermatogenesis in Tegula (Chlorostoma) tridentata (Potiez and Michaud, 1838) (Mollusca: Archaeogastropoda: Trochidae). AB - The basic environment for the generation of spermatozoa in the gastropods is a gametogenic compartment resulting from somatic and germ cells interaction. In arachaeogastropods however, such association has not been characterized. In this study at the light and transmission electron microscopy level, evidences are given that in T. (C.) tridentata, spermatogenesis is centrifugal and occurs around seminiferous tubules surrounding the lumen that is a blood vessel. This basic organization presents somatic cells interacting with germ cells. There are three types of spermatogonia: primary spermatocytes with proacrosomic granules, and spermatids that undergo the following spermiohistogenic events: 1. Nuclear chromatin condensation to form a short cylindrical nucleus with an anterior invagination containing the base of the axial rod and a posterior invagination containing the proximal centriole. 2. Polarization of mitochondria attached to the posterior nuclear membrane to integrate the midpiece. 3. Coalescence of proacrosomic granules in one acrosomic vesicle, polarization of the acrosomic vesicle in the anterior nuclear region and transformation of the acrosomic vesicle in the conical acrosomic complex with a subacrosomic cavity containing the axial rod. 4. Tail formation from the distal centriole. Apparently the supporting cells do not associate closely with the spermatids. Therefore, they would not perform a mechanical role in the generation of spermatozoa shape that is characteristic of the Trochidae and other archaeogastropod families. This spermatozoon is peculiar due to its prominent acrosome larger than the nucleus. PMID- 1293481 TI - Leaf ruminal digestion in Sorghum bicolor cultivars as influenced by water deficit. AB - A study was carried out on the effects of water deficit upon the specific leaf digestion of two sorghum cultivars: Novillero and Leoti Red. Using scanning electron microscopy it was established that after ruminal incubation, losses of structural integrity increased when the plants were submitted to drought conditions. This increase was marked in cv. Novillero after 48 h of digestion. For both cultivars, the phloem, mesophyll, parenchyma and epidermis were the most susceptible tissues to bacterial attack. The alterations in tissue disappearance during digestion, could partially explain the effects of water deficit upon the improvement in the nutritional quality of the two cultivars studied. PMID- 1293482 TI - Dehydroleucodine prevents ethanol-induced necrosis in the rat gastric mucosa. A histological study. AB - The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG). PMID- 1293483 TI - A light- and electron-microscopic study of the pineal complex of the ammocoete larva of the southern lamprey Geotria australis. AB - The pineal complex of larval Geotria australis lampreys has been examined by light- and electron-microscopy. The complex consists of a pineal organ and a smaller parapineal organ, the former being situated dorsal to the latter. It is concluded that the pineal organ is a functioning photoreceptor, with neural and endocrine output. The parapineal appears to be a more basic neuroendocrine organ without photosensory capability. Day-night comparisons of the pineal complex show no obvious differences in ultrastructure; this could be related to the chronobiological role of the complex as a constant monitor of ambient light levels, rather than a mere visual receptor that changes its sensitivity at night. PMID- 1293484 TI - Crystals in supporting cells of pineal organ in larval lamprey not likely to be pure guanine. AB - Spectrophotometry of larval pineal organs, digested in either 1 M HCl or 1 M NaOH, revealed peak absorbances at 253 nm and 268 nm, respectively. This result is not consistent with the view that the crystals found in lamprey pineals are chemically made of guanine. PMID- 1293485 TI - [The chitinases of aerobic sporulating bacteria isolated from different ecological sources]. AB - The chitinolytic activity of 171 strains of 15 species of spore-forming aerobic bacteria isolated from different ecological sources has been studied. 85 strains of the studied bacilli (50%) hydrolyzed colloidal chitin in a different degree. Among the cultures isolated from human and animal organism 60% of strains were characterized by the presence of extracellular chinases, among the collection strains--37%, among those isolated from soil and from insects--40 and 43%, respectively. The cultures of Bacillus subtilis as well as B. coagulans, B. megaterium and some other possessed the highest activity on the liquid medium. Some strains have been chosen for further research aimed at their possible use for biotechnology. PMID- 1293486 TI - [The lysogeny of Vibrio parahaemolyticus of serovar O4:K12]. AB - Lysogeny has been first established in strains of parahemolytic vibrios of serovar O4:K12. Moderate phages belonged to morphological group IV by home A. S. Tikhonenko's classification and were presented by one serological type. No correlation has been revealed between sensitivity to moderate phages of parahemolytic vibrios and specificity of "O"- or "K"-serotypes. PMID- 1293487 TI - [A method for determining the toxigenicity of micromycetes]. AB - A method is suggested to determine toxigenicity of microscopic fungi from genera Aspergillus, Penicillium, Fusarium, etc. which contaminate fodder, food products and environment objects. The method is based on the property of micromycetes isolated from fodder, food products and environment objects to produce mycotoxins under optimal conditions of their cultivation on the nutrient media. Their further extraction by the organic solvent, evaporation and emulsification of the extract and its peroral introduction to young female rats cause a disease and death of animals. The suggested method may be used for recognizing and preventing mycotoxicoses of farm animals and poultry. PMID- 1293489 TI - [Was a handshake enough?]. PMID- 1293488 TI - [Problems for discussion on the creation and use of bacterial preparations for the correction of the microflora of warm-blooded animals]. AB - Different aspects of interrelation between macro- and microorganisms are considered in the paper. The phenomenon of rapid translocation of the exogenic microflora into blood and organs of the hot-blood animals opened by the authors is analyzed in detail. Strategy and tactics of application of biopreparations from living microbiol cultures are discussed as based on the authors' experimental data as well as on numerous data from literature. PMID- 1293490 TI - Polymerase chain reaction: relevance for oral pathology. AB - The polymerase chain reaction (PCR) is a recent innovation in biotechnology for amplifying specific nucleic acid sequences by use of repeated cycles of DNA synthesis. Application of PCR has been extended to a wide variety of biological and medical disciplines; fields of application include molecular genetics, pathology, microbiology, forensic medicine, and infectious diseases. Because of its speed and powerful sensitivity, PCR has become a highly valuable method for detecting small amounts of target nucleic acid sequence with the caveat that it has certain limitations. Importantly, false-positive reactions can result from the amplification of contaminating DNA whereas false-negative reactions can result from introduction of inadequate numbers of primer sequences. The application of PCR in the context of oral pathology is presented along with a discussion of the utility of this technique to aid in the elucidation of the etiology of oral disease. PMID- 1293491 TI - [The first isolation of Torulopsis glabrata (Anderson) Lodder from dental granulomas]. AB - Three Torulopsis have been isolated from two hundred or so dental granulomas. Torulopsis glabrata has been observed in cases of ophthalmopathy, infections of the oral cavity, lung infections, endocarditis and septicaemia. Apical lesions due to Torulopsis glabrata are not typical of mycosis but are generic of dental granulomas. The histological granulomatous character prevails. Experimental infections have been obtained from this fungus. Human infections by Torulopsis glabrata have been described. These infections are induced particularly in subjects with their immunity systems depressed by prolonged cortisone therapy. Their systematic position and morphology in optical microscopy have been examined in accordance with current views. PMID- 1293492 TI - [In vivo and in vitro experimentation with the effects of chlorhexidine in patients who have undergone a periodontal intervention]. AB - The periodontal pack is often used to cover the surgical site after surgery, even when associated with local applications of preparations containing chlorexidine, in order to obtain an antiseptic protection. However many people question whether the drug effectively succeeds in penetrating the pack, or if the presence of the pack itself doesn't obstruct the action of the medication. The aim of this work is to evaluate the efficiency of the clorexidine in the surgical area with and without a periodontal pack. In a first stage, a case was chosen and contemporary operated on in two different but anatomically similar sites at the same time. One of the two sites was covered with a chlorexidine gel for the following week, whilst the other was left without medication. After seven days the stitches removed from the two different sites were placed in culture mediums to number and classify the bacterial strains present. In the second stage of the experiment, another eight patients were operated on in the same way, and the two sites covered with periodontal packs. In one of the two sites a layer of chlorexidine gel was positioned under the pack, and the chlorexidine above and on the sides of the pack was continually renewed throughout the week following the operation. The other site was not treated. The results obtained show that the pack partially reduces the action of the drug medication, probably because an insufficient amount reaches the site. The activity and efficiency of chlorexidine against the strains of bacteria found in vivo were tested in vitro. The chlorexidine destroyed all of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293493 TI - [The action on bacterial plaque of the mastication of a sorbitol chewing gum]. AB - The authors made a clinical evaluation of mastication of sorbitol chewing gum and its interference on plaque accumulation on teeth in 14 volunteers, 10 men and 4 women with an age average of 27 y.o., who joined both control and gum groups for 1 or 2 or 3 days. Both groups, after perfectly cleaning their teeth, were requested to avoid any measure of oral hygiene for the whole time of the study and the gum group was advised to chew one sorbitol chewing gum immediately after every assumption of solid food for unless than 30' minutes with a minimum of 4 pieces a day (after breakfast, after lunch, during the afternoon, after dinner). They were supplied with one of two most diffused sorbitol chewing gums in Italy: Vivident in 8 and Happydent in 6 cases. The choice of sorbitol was made because it can be considered a non-cariogenic sweetener and because in our country it is the most used in the so called "senza zucchero" gums and sweets. Plaque extension was evaluated by Quigley-Hein plaque index with the same procedure of the original work and taken as a parametric value in order to apply parametric tests as media, normal distribution, standard deviation, variance, Student's tests, etc. These evaluations were made on Ramfjord's teeth: 1.6, 2.1, 2.4, 3.6, 4.1, 4.4 each one divided in two half. Results, so processed, showed a significant reduction (-0.96%; p < 0.01) of plaque index for 1 day with best effect on vestibular half of frontal teeth (p between < 0.01 and < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293494 TI - [A scanning electron microscope assessment of the changes induced by wear on subsonic endodontic instruments]. AB - The aim of the present work was to study the wear of a special kind of subsonic instruments with usage. We have examined with scanning electron microscope new and used instruments: the first to estimate the features and degree of final touches; the second to examine how they wear after 1, 3 and 5 minutes. We tested for each period 3 instruments per size. In all we controlled 72 instruments. The results of the study show that after 5 minutes the instruments are very worn. PMID- 1293495 TI - [Anatomicosurgical comments on the importance of the spinal accessory nerve]. AB - The preserved integrity of the spinal accessory nerve plays an extremely important role in cervico-facial surgery since the majority of surgical approaches involve this nervous structure. Following a short historical outline of the surgical method, the Authors illustrate the anatomo-topographical aspects and anatomo-surgical problems. A number of points emerge from a review of the literature which are vital to isolate the spinal accessory nerve: 1) the transversal apophysis of the atlas is particularly prominent in the retrostyloid space and lies half-way across an imaginary horizontal segment connecting the mastoid process with the angle of the mandible; 2) the posterior edge of the sternocleidomastoid muscle at approximately six centimetres from the mastoid process; 3) the nervous point of Erb located at the point where the superficial branches of the cervical plexus emerge from the posterior edge of the sternocleidomastoid muscle (the nerve generally emerges from the posterior edge of the sternocleidomastoid muscle two centimetres above this point and two centimetres below it the nerve meets the anterior edge of the trapezius). This is followed by an analysis of the possible complications deriving from lesions to this vital nervous structure. The resection of the spinal accessory nerve leads to the so-called "shoulder syndrome" mainly due to the denervation of the trapezius. This syndrome is characterised by the onset of regional pain, the typical deformation of the shoulder joint and functional deficit. The deformation is provoked by the decreased muscular strength of the superior and middle portion of the trapezius manifested as the rocking of the shoulder and a higher superointernal angle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293496 TI - [Primary reconstruction of the anterior sublingual sulcus with a nasolabial flap after the resection of a malignant neoplasm]. AB - The reconstruction of the loss of substance from the oral floor following demolitive cancer surgery aims to guarantee adequate tongue movement and the consequent preservation of phonatory and swallowing functions, as well as the possibility of using prosthetic rehabilitation. Large defects are resolved using musculocutaneous or free vascularised flaps, whereas smaller defects may be closed by first intention using alveolo-lingual suture. There are a number of drawbacks to this method: occurrence of fistulas immediately after surgery and secondary ankyloglossia. It is then necessary to resort to a second operation using dermoepidermic graft and plastic surgery of the oral floor to liberate the tongue. These problems may be resolved using a nasolabial flap. The flap can be prepared using either an upper or lower peduncle, it is relatively simple to perform and does not significantly prolong operating times. The contemporary dissection of the neck with ligature of the facial artery does not in our experience significantly influence flap vascularisation. The main drawback is the limited size of the flap (on average it is 6-7 cm long with a maximum width of 3 4 cm at the base. The upper edge is equally placed 7-10 mm from the medial side). The flap must be sufficiently thick to ensure an adequate blood supply to subcutaneous tissue, but the dissection plane must be sufficiently near the surface to preserve the facial nerve. It is important to prepare the graft bed so as to avoid creating tension after suture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293497 TI - [The orthosurgical correction of 2 cases of Angle class II div I]. AB - An orthosurgical technique comprising maxillary expansion using Burstone screws associated with multiple corticotomy, repositioning of the bone basis and pre- and postoperative orthodontics was used to correct two cases of Angle's class dysgnathia with involvement of both the bone basis and alveolodental component. The outcome was satisfactory in that a good esthetic result was achieved together with normal and functional occlusion which was stable over time. PMID- 1293498 TI - From diet to DNA: dietary patterning of gene expression. AB - The role of molecular biology in understanding structure/function relationships as well as the influence of metabolic processes on host nutrition is becoming increasingly important. Not only is this field having a major effect in elucidating the detailed structure of nutritionally important enzymes but it is also allowing the nutrition scientist to study metabolic function and the significance of different pathways in whole animals. In this review, the use of gene transfer studies, in particular, the creation of transgenic animals to study mechanisms in which nutrients may regulate gene expression is discussed. Although these studies are presently quite specific, it is envisioned that these studies will ultimately lead to a better understanding of dietary host interactions, which may lead to the ability of the clinician to optimize dietary intake in order to more favorably modify metabolic disorders. PMID- 1293499 TI - Growth hormone and nutritional support: adverse metabolic effects. AB - The use of growth hormone in clinical nutritional support has received considerable attention over the past decade. The most encouraging results have been improved nitrogen retention and protein synthesis in the presence of hypocaloric nutritional support. Adverse effects, however, can limit the clinical usefulness of this technology. In the following case study, an obese 71-year-old man with a history of chronic obstructive pulmonary disease remained ventilator dependent 2 months following anterior cervical fusion and had severe depletion of visceral proteins despite nitrogen equilibrium. He was treated with 10 mg of recombinant human growth hormone (Genentech) subcutaneously every other day while also receiving nutritional support. We hypothesized that growth hormone administration could promote both protein synthesis and the development of muscle mass, particularly in the respiratory muscles, without increasing nutrient intake and, therefore, without increasing CO2 production. The patient, however, developed two potentially life-threatening adverse effects: hyperglycemia and fluid retention. The severity of these adverse effects led to discontinuation of this mode of therapy. PMID- 1293500 TI - Applications of biotechnology in nutrition. PMID- 1293501 TI - Limiting bacterial contamination of enteral nutrient solutions: 6-year history with reduction of contamination at two institutions. AB - Running enteral nutrient solution (ENS) bacterial contamination logs that were collected over a 6-year time frame are presented. At hospital A, reconstituted ENS were prepared by the pharmacy department in bulk and were frozen in the final container. These solutions were cultured and counted after 12 hours of storage at room temperature to stimulate this institution's hang time. Major reductions in ENS bacterial counts occurred after improvements in sanitation, a reduction in solution hang time, the conversion to the use of sterile water for dilution and reconstitution of ENS, and most dramatically, after the incorporation of a preservative (potassium sorbate) to reconstituted ENS. At hospital B, ENS usage consisted of canned feedings that were prepared by nursing personnel and were transferred to the feeding container at the bedside. Reductions in final counts of contamination of ENS occurred after procedural changes, which included container changes every 24 hours, use of sterile water for dilution, cleansing of can lids with alcohol swabs before use, rinsing and air drying of intermittent feeding containers between feedings, and limiting feeding container fills to 4 hour hang time quantities. At both institutions, the value of an ongoing three class enteral quality control program with a defined acceptance/rejection criteria was demonstrated in that ENS contamination was reduced to acceptable levels comparable with federal standards for milk and dairy products. PMID- 1293502 TI - Animal models in human nutrition research. AB - Animal models are used extensively in nutritional research. Studies with animal models may not provide a discussion of the applicability of the model to humans, and seldom do such studies discuss the limitations of the model. This article presents information that is targeted toward the nutrition support practitioner about the use of animal models in nutritional research. The rationale for using animal models and the applicability to humans, the limitations of applicability, and the unique opportunities related to animal models is presented. PMID- 1293503 TI - JCAHO reports field testing of six indicators for home infusion therapy. PMID- 1293504 TI - Molecular biology in nutrition. AB - Recent progress in the field of molecular biology has had a considerable effect on both basic and applied clinical nutrition and offers even greater promise for the future. It is important for individuals working in clinical nutrition, as well as basic science investigators, to have an understanding of the fundamental concepts of molecular biology in order to be able to evaluate and apply new approaches to clinical problems as they become available. The purpose of this review is to provide those who are not molecular biologists with a brief overview of the fundamental concepts of molecular biology and then to describe a number of the recent applications of molecular biological methods and tools in the field of nutrition. PMID- 1293506 TI - Lipogenesis from n-butyrate in colonocytes. Action of reducing agent and 5 aminosalicylic acid with relevance to ulcerative colitis. AB - Cell membranes of colonic epithelial cells (CEC) in ulcerative colitis show structural abnormalities which are specific to the disease and which suggest impaired lipogenesis in CECs. Lipogenesis from [1-14C]-n-butyrate, the chief oxidative fuel of colonic epithelial cells, was measured in isolated CECs under control conditions, with or without glucose and in the presence of mercaptoacetate, a major reducing agent in the colonic lumen. Glucose significantly (p < 0.01) stimulated lipogenesis from [1-14C]-butyrate which was reversed by 5 mM mercaptoacetate. Mercaptoacetate significantly diminished CEC thiolase activity (EC 2.3.1.9). 5-Aminosalicylic acid reversed the adverse effects of mercaptoacetate in the saponifiable fraction of extracted lipids. Changes in lipogenesis due to colonic luminal reducing agents would affect the barrier function of CECs a feature relevant to the disease process of ulcerative colitis. PMID- 1293505 TI - Antioxidant drug mechanisms: transition metal-binding and vasodilation. AB - In our work evaluating the antioxidant properties of a number of cardiovascular drugs, we have emphasized the importance of lipophilicity as a property contributing to antioxidant potency. Thus, the dihydropyridine calcium channel blockers and propranolol, one of the most lipophilic beta-blockers, were found to exhibit the greatest potency in membrane and cellular models. Both beta-blockers and calcium channel blockers are classified as antihypertensive agents. We found that the specific chemical moieties of various drugs may participate in the antioxidant mechanism of action. While reviewing relevant work from the past literature, it became apparent that some of the chemical moieties of antihypertensive and vasodilator drugs may bind transition metals. Thus, this present review focuses on common properties of transition metal-interaction that are shared, to a greater or lesser degree, by a number of vasoactive drugs and chemical agents. Although this observation has been pursued by other investigators in the past, we submit that the potential relevance to the newer pharmacological agents needs to be explored further. In addition, new information regarding the role of transition metals and free radicals involving vascular cells focuses greater importance on transition metal-interaction as a potential mechanism in vasodilation. This review does not intend to be inclusive of all chemical structures capable of binding transition metals; only those that are clinically relevant will be considered in some detail. Potential mechanisms of metal-chelating actions leading to vasodilation are also discussed. PMID- 1293507 TI - An AP-1-like motif in the first intron of human Pro alpha 1(I) collagen gene is a critical determinant of its transcriptional activity. AB - The first intron of the human Pro alpha 1(I) collagen gene contains an orientation-dependent enhancer composed of both positive and negative cis-acting elements involved in the transcriptional regulation of this gene. Deletion of a 360 bp Sau 3A intronic fragment spanning nucleotide +494 to +854 (S360) resulted in dramatic down-regulation of pCOL-KT (Thompson et al., J Biol Chem 266: 2549 2556, 1991). Using a DNaseI protection assay, we demonstrate a single footprint located at +590 to +615 in the S360 fragment; nuclear extracts prepared from mesenchymal and nonmesenchymal cells exhibited similar binding characteristics. A double stranded oligonucleotide representing a consensus Ap-1 binding sequence competed with S360 for binding. In contrast to what occurred in response to S360 deletion which was always accompanied by reduced expression, the deletion of the Ap-1 binding site (+598 to +off) caused either increased or decreased expression of the reporter gene depending on the target cell. Site-directed mutations in the Ap-1-like cis-element of Pro alpha 1(I) were also tested in transient expression assays. Consistent with the paradoxical results of Ap-1 deletion, we observed that the functional consequences of mutations in the Ap-1 site also varied in different cells. In A204 cells, one point mutation, which resulted in the loss of protein binding to S360, led to increased CAT activity while another point mutant, which retained binding of the Ap-1 like trans-acting factor(s), showed decreased CAT expression. The effects of these two mutations in the HFL-1 cells were exactly opposite of what was seen for A204 cells. Based on these observations, we postulate that the Ap-1 site plays a critical role in the transcriptional activity of the human Pro alpha 1(I) gene. The implications of an apparently dual mode of regulation through a single cis-regulatory element are discussed. PMID- 1293508 TI - Morphological changes in Krebs II ascites tumour cells induced by insulin are associated with differences in protein composition and altered amounts of free, cytoskeletal-bound and membrane-bound polysomes. AB - A three-step sequential detergent/salt extraction procedure was used in order to isolate three distinct subcellular fractions containing free (FP), cytoskeletal bound (CBP) and membrane-bound polysomes (MBP), respectively, from Krebs II ascites cells (Vedeler et al., Mol Cell Biochem 100: 183-193, 1991). The purpose was to study changes in the distribution of polysomes in these three fractions during long-term incubation with insulin under either stationary conditions or in roller suspension culture. Insulin caused a redistribution of polysomes between FP, CBP and MBP fractions. The hormone appeared to promote an entry of ribosomes into polysomes both in CBP and MBP populations. When cells were grown in stationary culture in the presence of insulin and thus promoted to attach to the substratum and undergo morphological changes, a diversion of ribosomes from CBP into MBP was observed. The level of protein synthesis was apparently very high in this latter fraction since more than 70% of ribosomes were in polysomes. Morphological changes observed following insulin treatment were accompanied by a shift of certain proteins among subcellular fractions (for example actin and p35). The fibronectin content was about 20% higher in attached compared to non attached cells. The results suggest that morphological changes induced by stimulation with insulin are associated with an increased activity of MBP, presumably reflecting a requirement for an increased synthesis of membrane proteins. PMID- 1293509 TI - Effects of alloxan and ninhydrin on mitochondrial Ca2+ transport. AB - Alloxan at millimolar concentrations slightly inhibited the velocity of Ca2+ uptake by isolated rat liver mitochondria irrespective of the free Ca2+ concentration between 1 and 10 microM and was an effective concentration dependent stimulator of mitochondrial Ca2+ efflux. Ninhydrin also slightly inhibited the velocity of mitochondrial Ca2+ uptake but only at free Ca2+ concentrations above 5 microM. However, ninhydrin was a strong stimulator of mitochondrial Ca2+ efflux even at micromolar concentrations, 10-50 times more potent than alloxan. The mitochondrial membrane potential was reduced 10-20% at most by alloxan and ninhydrin. Alloxan and ninhydrin also stimulated Ca2+ efflux from isolated permeabilized liver cells. When isolated intact liver cells had been pre-incubated with alloxan or ninhydrin before permeabilization of the cells the ability of spermine to induce mitochondrial Ca2+ uptake was abolished. Glucose provided the typical protection against the effects of alloxan on mitochondrial Ca2+ transport only in experiments with intact cells but not in experiments with permeabilized cells or isolated mitochondria. Therefore glucose protection is apparently due to inhibition of alloxan uptake into the cell. Glucose provided no protection against effects of ninhydrin under any of the experimental conditions. Thus both alloxan and ninhydrin are potent stimulators of Ca2+ efflux by isolated mitochondria but very weak inhibitors of the velocity of mitochondrial Ca2+ uptake. The direct effects of ninhydrin on mitochondrial Ca2+ efflux may contribute to the cytotoxic action of this agent whereas the direct effects of alloxan on mitochondrial Ca2+ transport require concentrations which are too high to be of relevance for the induction of the typical pancreatic B-cell toxic effects of alloxan. However, the effects on mitochondrial Ca2+ transport during incubation of intact cells which may result from the generation of cytotoxic intermediates during alloxan xenobiotic metabolism may well contribute to the pancreatic B-cell toxic effect of alloxan. PMID- 1293510 TI - Effect of n-3 and n-6 fatty acids on hepatic microsomal lipid metabolism: a time course study. AB - The present study examines the time dependent effects of n-6 and n-3 polyunsaturated fatty acids on liver microsomal lipid metabolism in FVB mice fed a diet supplemented with a mixture of free fatty acids (mainly 18:3n-6 and 20:5n 3) at 25 mg/g diet. Significant changes in the fatty acid composition of total liver and microsomal lipids were observed after 7 days on the diets. Thereafter, some animals remained on the same diet while others were fed a diet supplemented with hydrogenated coconut oil (HCO). With the exception of 20:5n-3 which showed a slower recovery, establishment of the HCO pattern was rapid indicating that the diet-induced changes could be easily reversed. The unsaturation index, the cholesterol/phospholipid ratio and the microviscosity of the microsomal membranes were not affected by these dietary manipulations. Unsaturated fatty acid supplementation reduced the activity of delta 9 desaturase by 50%. Feeding the HCO diet to mice previously fed the EPA/GLA diet led to a progressive increase in delta 9 desaturase activity, reaching 80% of the day zero values after 14 days. The monoene content of hepatic total lipids reflected, in most cases, the changes in enzyme activity. This study shows that a low dose of a n-3 and n-6 free fatty acid mixture increases the quantities of members of the n-3 family, without loss of n-6 fatty acids in microsomal membranes and modifies the activity of delta 9 desaturase without altering the microsome physicochemical parameters. PMID- 1293511 TI - Cardiac dilatation associated with collagen alterations. AB - There is a complex collagen network in the heart. Various components have been identified and generally on the basis of form and position some functions have been ascribed to one or another of these components. Since the various components all appear to be connected in a hierarchial network of some type assigning function is not difficult but demonstrating a given function is somewhat hazardous. We have demonstrated that two I.V. infusions of disulfide reagents one week apart activates a collagenolytic system that results in near complete loss of the collagen struts that interconnect myocytes, the collagen struts that connect capillaries to all adjacent myocytes and the weave complex that surrounds groups of myocytes. Increases in pre load or afterload result in responses indicating that the disulfide treated animals generate pressure equal to or greater than the control hearts, thus, the treatment has no affect on either myocyte contractility or force delivery to the ventricle. However, static pressure volume measurements in the disulfide treated animals are shifted far to the right indicating marked dilatation of the ventricle and increase in distensibility. This indicates that the weave complex contributes to the initial rectilinear portion of the pressure volume curve. PMID- 1293512 TI - Menadione-resistant Chinese hamster cell variants are cross-resistant to hydrogen peroxide and exhibit stable chromosomal and biochemical alterations. AB - We have investigated the antioxidant properties of V79 Chinese hamster cells rendered resistant to menadione by chronic exposure to increasing concentrations of this quinone. MD1, a clone of resistant cells, was compared to the parental M8 cells; the former showed increased activity of catalase (3 fold), glutathione peroxidase (1.6 fold) and DT-diaphorase (2.6 fold), as well as an increase in glutathione (3.2 fold). Although one of the products of menadione metabolism is superoxide anion, no changes in total superoxide dismutase activity was observed in MD1 cells. MD1 menadione resistant cells were also resistant to killing by hydrogen peroxide and contained tandem duplication of chromosome 6. A similar duplication of chromosome 6 was seen in several independently derived menadione resistant clones and therefore seems closed linked to the establishment of the resistance. Upon removal of menadione from the medium, some of these properties of MD1 cells, viz., resistance to menadione, elevated glutathione levels, and glutathione peroxidase activity, were lost and the cells resembled M8 cells. However, resistance to H2O2, elevated catalase activity and the duplicated chromosome remained stable for more than 40 cell passages in the absence of menadione. The increase in catalase activity was correlated with an increase in catalase mRNA content and a 50% amplification of catalase gene, as determined, respectively, by Northern and Southern blot analysis. The role of the chromosome 6 duplication in resistance to oxidative stress remains to be established. It is not responsible directly for elevated catalase levels since the catalase gene is on chromosome 3. PMID- 1293513 TI - A flea bite. PMID- 1293514 TI - Toward a new paradigm for nursing. PMID- 1293515 TI - Public policy analysis for registered nurses in a baccalaureate curriculum. AB - As nurses become more involved in the macro-decision-making arena, they need policy analysis skills in order to make effective recommendations on policy alternatives. Dunn's policy analysis framework, useful for examining and understanding policy issues, is relevant to nursing education and practice and provides guidance for effective action. This framework guided an educational experience for registered nurse (RN) students in a baccalaureate nursing program. The students participated in community-based policy analysis, examining public policies affecting the health of individuals, families, groups, and populations. Dunn's framework and this policy experience can be incorporated into formal education courses or continuing education programs. PMID- 1293516 TI - AIDS and the Rehabilitation Act. PMID- 1293517 TI - People's Community Clinic: collaboration in the Third World. AB - A West African government undertook to improve primary health care (PHC) training of mid-level health workers. In partnership with a neighboring squatter settlement, the premiere local training institution created a community-sponsored clinic, providing low-cost, PHC services, and a birthing center, as well as student experiences. Their collaboration in mobilization, research, planning and operations are described. Their success should encourage other educational and training institutions to consider a similar approach. PMID- 1293518 TI - Improving home health care for the Navajo. AB - Home health care clients on the Navajo reservation present complex nursing problems that require interventions that are culturally sensitive. A collaborative project was developed that used the skills of researchers, clinicians, and members of the Navajo culture to develop culturally appropriate nursing care. Traditional life themes, values, and beliefs of the Navajo related to health and illness are described with examples of how the project facilitated home health care for Navajo clients. PMID- 1293519 TI - Nursing administration at the turn of the century. PMID- 1293520 TI - Involving the target population and their providers in evaluation of substance abuse videos. AB - Substance abuse prevention and case finding are serious challenges to nurses who care for pregnant women and their infants. Audiovisual media can be useful in helping these nurses and their patients. This article discusses the insights of pregnant, low-income, minority women and their health care providers regarding selected substance abuse prevention videos. Focus group sessions were used to elicit valuable information, not only about reactions to substance abuse media but on their use in facilitating communication between patients and providers. Through this process, collaborative relationships were fostered among pregnant inner-city women, nurse clinicians, and nursing faculty, all of whom share a concern about substance abuse and an interest in working together to combat the problem. PMID- 1293521 TI - Evaluating our new health care plan. PMID- 1293522 TI - A collaborative process and framework for nursing research. AB - Currently, there is a need for outcome research in nursing practice. To facilitate practice-based research, collaboration between education and service is essential. Although a few studies have been reported in the literature on partnerships between education and service, there is a need to describe the nature of a successful collaborative research process between a university college of nursing and a medical center. Nursing leaders from a university college of nursing and a medical center developed a collaborative framework and process by which to obtain funding for research. The following elements were crucial to the framework and facilitated the research process: commitment from leaders and individuals; concentration on positive outcomes and communication between institutions and within groups; matching of individuals; consensus on issues; and adherence to deadlines. The major benefits to this partnership are the enhancement of and opportunity for intradisciplinary research. The process provides a study site for the research and prepared faculty to develop it. All of the above elements factors contribute to a collaborative working arrangement and ensure successful outcomes for future projects. PMID- 1293523 TI - Ethics of writing in nursing: responsible mentorship. PMID- 1293524 TI - Retrospective study of optometric referrals. AB - We undertook a retrospective study of the referral patterns of optometrists. During the study period 13,107 patients had been seen, of whom 2.86% had been referred. Of the referred patients, 66.67% were referred to an ophthalmologist via the general practitioner, 25.87% to their general practitioner alone, and 7.47% directly to an ophthalmologist. The conditions for which patients were referred are given along with information on any supplementary tests used. The effect of practitioner age and seasonal variations on referrals was also determined. The role of the optometrist in screening for ocular disease is discussed. PMID- 1293525 TI - Screening for glaucoma: age and sex of referrals and confirmed cases in England and Wales. AB - This paper is based on a prospective survey covering 275,600 sight tests by optometrists in England and Wales. It analyses the age and sex distribution of 1402 referrals for suspected glaucoma and 456 confirmed cases of the disease. The proportion of sight tests which led to a confirmed case increased with age, for both sexes, to a maximum at approximately 70 years, and then tended to decline. Cases of glaucoma in people aged 36-51 years accounted for about a tenth of the total, which is more than is generally recognized. Wider adoption of routine tonometry for middle aged people would help to ensure that these cases are detected at an early stage. Confirmed cases of glaucoma in which raised intraocular pressure had not been given as a reason for referral, i.e. probable low tension glaucomas, increased from 5% of patients < 51 years old to 13% of patients > 75 years old. Glaucoma was found to be much more common in men. PMID- 1293527 TI - Variability of fixation disparity and accommodation when viewing a CRT visual display unit. AB - Fixation disparity and accommodation were measured while subjects viewed a target on a cathode ray tube at a 50 cm viewing distance. The psychophysical method of sequential testing was used. For measuring fixation disparity a series of brief dichoptic nonius targets was presented and the direction of perceived misalignment was reported by the subject. From these responses the psychometric function of fixation disparity can be derived which gives not only the mean fixation disparity but also the range of fluctuation during the period of measurement. During a 5 min period, this range was +/- 1.5 min arc averaged over subjects, when expressed as the range in which instantaneous fixation disparity fell with a probability of 68%. Repeated measurements on 5 days within 2 weeks gave a larger range of +/- 2 min arc. However, individual results can differ considerably from these average values. Repeated measurements and the analysis of the psychometric function can provide a more complete description of individual binocular status than is obtained with a single adjustment of continuously visible nonius targets. Laser optometry revealed that, compared to the stimulus distance of 50 cm, accommodation lagged behind in the range 1-2 D. The two display modes of bright characters on dark background and vice versa gave very similar results. PMID- 1293526 TI - Evaluation of two infrared autorefractors in pseudophakia. AB - We investigated the viability of using an objective infrared autorefractor to identify high corneal astigmatism (> 3.00 D) in a pseudophakic population. The eyes of 91 patients, who had recently undergone cataract extraction and intraocular lens implanation, were refracted manually and using two infrared autorefractors, a Canon RK-1 and a Nikon NR-2000. Autorefractor measurements were repeated to provide estimates of reliability for each instrument. LogMAR visual acuities were also recorded with both the manual and autorefractor corrections. Approximately 75% of repeat autorefractor measurements were within 0.50 D of the initial readings, and about 75% of measurements were within 1.00 D of the manual refractions. Visual acuities with manual corrections were, on average, one line better than with autorefractor corrections. By validating the autorefractors against manual refraction, the efficiency of the autorefractors for detecting astigmatism > 3.00 D was calculated. Setting the cut-off criterion to ensure high sensitivity (95%), so that almost all patients with > 3.00 D were detected, resulted in both instruments having a poor specificity of about 40%. PMID- 1293528 TI - Rapid- and slow-velocity vergence eye movements. AB - Previously we have measured rapid-velocity vergence responses to targets at different distances that provided no disparity or accommodative stimulation. To evaluate the possibility that this rapid-velocity vergence occurs during saccades, the latencies of eye movement between two long dim luminous rods were compared under two conditions. Rapid-velocity vergence with an average latency of approximately 300 ms was elicited when subjects alternately viewed horizontal rods at distances of 38 and 78 cm, and with a vertical separation of 5.2 degrees. Horizontal saccades with a comparable latency were measured when the rods were equidistant and oriented vertically. The correlation between the mean latencies of vergence and saccadic movements was 0.97, suggesting that the two movements occurred together. In a second experiment vergence responses were measured when the subject looked between a bright vertical line on a screen at 76 cm and a second pair of lines (vertically displaced between 0.15 degrees and 3 degrees) with crossed disparity to simulate a target at 38 cm. Slow-velocity vergence often occurred alone when the vertical separation between targets was small; rapid-velocity vergence intruded when the separation between the targets was larger. The results can be accounted for if proximity and disparity stimulation act through a single vergence controller, the output of which produces slow- or rapid-velocity vergence depending upon whether the saccadic system is concurrently active. PMID- 1293529 TI - Method for identifying amblyopes whose reduced line acuity is caused by defective selection and/or control of gaze. AB - Three visual tests were administered to a group of 15 amblyopic children, 15 adult amblyopes and two age-matched control groups, each of 20 subjects. Test results comprised visual acuity for recognizing high contrast letters presented in line (i.e. Snellen) format, isolated-letter format and repeat-letter format. The classical Snellen format confounds the effects of gaze control defects with the effects of adjacent contours on a patient's ability to recognize a foveated letter. We designed a repeat-letter format intended to unconfound these effects. The repeat letter format is much less sensitive to gaze control defects, and somewhat more sensitive to adjacent contour interactions than is the Snellen format. We report that amblyopic eyes can be subdivided empirically into three repeat-letter categories: repeat-letter acuity significantly better than Snellen acuity; repeat letter acuity not significantly different from Snellen acuity; and repeat letter acuity significantly worse than Snellen acuity. We report that this subdivision cuts across the clinical subclassification of amblyopia and also across the crowding/no crowding subclassification. We suggest that, rather than abnormal lateral interactions, defective selection and/or control of gaze is an important factor in depressed visual acuity in amblyopic eyes of the first repeat letter category but not for the third type, in which abnormal lateral interactions may be important. To test the hypothesis that the response to patching and refractive therapy may be less satisfactory in our first category of amblyopic eyes, we are carrying out a prospective study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293530 TI - Contribution of accommodation and disparity-vergence to transient nearwork induced myopic shifts. AB - Many investigations have attempted to demonstrate a relationship between sustained near-vision and the aetiology of environmentally-induced myopia, but it remains unclear whether myopic development relates to the actions of either accommodation or vergence. The present study investigated the effect of varying the disparity-vergence demand during a near-vision task while maintaining the accommodative stimulus constant. We required 20 young subjects to perform a near task (viewing distance = 20 cm) for 20 min through base-in, zero power and base out prisms. The magnitude of the prisms for each individual corresponded to one third their near vergence range. Pre- and post-task measurements of refractive state were determined objectively using an infrared optometer, with post-task readings being recorded over the initial 50 s following task completion. The results indicated no significant difference between the transient far-point shift for the three disparity-vergence conditions. However, combining data across conditions, a significant, mean shift in the myopic direction of 0.14 D was observed during the 10-20 s period immediately following task completion which dissipated within 20-50 s post-task. These findings suggest that the transient post-task myopic shift was not related to the output of disparity-vergence. PMID- 1293531 TI - Effect of attention on the VEP in binocular and monocular conditions. AB - To study the effect of voluntary concentration on the visual evoked potential (VEP) with monocular and binocular rivalry stimulation, pattern reversal VEPs were recorded using 5.5 min arc and 50 min arc check sizes. Subjects viewed the VEP stimulus with the left eye and a light emitting diode (LED) with the right eye. They were asked to concentrate on either the VEP stimulus or the LED. The two targets were arranged so that the left eye remained accurately focused on, and directed to, the centre of the VEP stimulus throughout the recordings. The binocular VEP wave became attenuated when the subject concentrated on the LED. The wave was reduced to around two-thirds of the amplitude present when concentrating on the VEP stimulus. This reduction in the VEP amplitude is considered to be due to a binocular interaction because there was a lack of amplitude attenuation when the experiment was repeated with monocular conditions. The results also suggest that the wave is smaller when the non-dominant eye receives the VEP stimulus compared with that when the dominant eye is stimulated by the VEP target. PMID- 1293532 TI - Relationship between axial length and chromatic refraction of the eye. AB - A new mathematical expression is derived to provide an estimate, alpha x, of the axial length of the human schematic eye. Approximations in the expression are made after considering effects in the Gullstrand-Emsley schematic eye. Parameters required to solve the expression are, for two wavelengths, the refractive indices of the humours, the focal power of the cornea and refractive errors in two states of accommodation. Unlike recognized optical methods, additional intraocular parameters are not required. For emmetropic variants of the Gullstrand-Emsley schematic eye with axial lengths between 19 and 27 mm, alpha x is within 0.06 to 0.26 mm of the actual value. Furthermore, alpha x is essentially independent of variations in the refractive indices of the crystalline lens. However, the estimate of alpha x is critically dependent on the accuracy of values assigned to the parameters. For that reason, the model is considered impractical for clinical application. PMID- 1293533 TI - Refractive plasticity of the developing chick eye. AB - We have developed a lightweight plastic goggle with rigid contact lens inserts that can be applied to the eyes of newly hatched chicks to explore the range and accuracy of the developmental mechanism that responds to retinal defocus. Convex and concave lenses of 5, 10, 15, 20 and +30 D were applied to one eye on the day of hatching. The chick eye responds accurately to defocus between -10 and +15 D, although hyperopia develops more rapidly than myopia. Beyond this range there is first a levelling off of the response and then a decrease. The resulting refractive errors are caused mainly by increases and decreases in axial length, although high levels of hyperopia are associated with corneal flattening. If +/- 10 D defocusing lenses are applied nine days after hatching the resulting myopia and hyperopia are equal to about 80% of the inducing power. After one week of inducing myopia and hyperopia with +/- 10 D lenses, the inducing lenses were reversed. In this case, the refractive error did not reach the power of the second lens after another week of wear. Instead, astigmatism in varying amounts (0-12 D) was produced, being greater when reversal was from plus to minus. Finally, astigmatism can also be produced by applying 9 D toric inducing lenses on the day of hatching. The astigmatism produced varies from 2 to 6 D, and the most myopic meridian coincides with the power meridian of the inducing lens. This astigmatism appears to be primarily due to corneal toricity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293534 TI - Twice-daily use of a chlorobutanol-preserved artificial tear on rabbit corneal epithelium assessed by scanning electron microscopy. AB - Female pigmented rabbits received two drops of a chlorobutanol 0.5%-preserved, polyvinyl alcohol-based artificial tear at 21.00 h and 09.00 h for 1, 2, 3, 6 or 12 consecutive days. The animals were killed at 15.00, 6 h after the last treatment. Scanning electron microscopy of the corneal epithelial surface at x 200 magnification revealed only occasional cell exfoliation averaging < 8% of the surface analysed at central, mid-peripheral and peripheral sites, showing minimal cytotoxic effects. The level of exfoliation was maximal after 2 to 3 days treatment and then returned to close to zero, so the eye adapts to repeated use of the artificial tears. Evaluation of the surface microplicae of the cells at x 15,000 indicated subtle, but distinct, changes in what might be the mucus material associated with the cell surface, especially after 2 and 3 days treatment. PMID- 1293535 TI - Meridional profiles of variance-covariance of dioptric power. Part 1. The basic theory. AB - It has recently become possible to calculate and represent variation or spread of dioptric power in a meaningful way. This is important for the proper analysis and interpretation of data on dioptric power in a number of areas of the vision sciences. The representation takes the form of a symmetric matrix of six (usually) variances and covariances. Although the matrix is satisfactory for several formal statistical purposes, such as the testing of hypotheses, it does not give an intuitively satisfactory picture of the extent and nature of the variation, nor is it easy to interpret in a way that could be useful to the researcher or clinician. A useful graphical representation of variation can be constructed from the variance-covariance matrix. It consists of curves that show the meridional dependence of the variation. These meridional profiles of variation give a complete and intuitively satisfactory picture of the nature and extent of the variation of power and are potentially of general use to researcher and clinician. A complete theoretical basis is provided for the construction of meridional profiles of variation of dioptric power. An accompanying paper employs the theory to construct profiles for a number of representative samples of dioptric power. PMID- 1293536 TI - Meridional profiles of variance-covariance of dioptric power. Part 2. Profiles representing variation in one or more of sphere, cylinder and axis. AB - Meridional profiles of variation of dioptric power are constructed. Using the basic theory developed in an accompanying paper, samples are selected in a systematic way to illustrate variation only in sphere, only in cylinder and only in axis, and in all possible combinations of sphere, cylinder and axis. For each of the seven samples, scatter plots are constructed together with ellipsoids that represent the estimated distribution of powers in the population from which the sample was taken. The surfaces of the ellipsoids are surfaces of constant probability density within which 95% of the population is calculated to lie. The scatter plots and distribution ellipsoids are plotted in a three-dimensional space called h-space. Meridional profiles of variation are constructed for each of the samples. Properties of the profiles are discussed. Meridional profiles are also presented for eyes before and after radial keratotomy. Among other things, the profiles show meridians of greatest and least variation and are intuitively satisfying. They are potentially useful for the researcher and clinician including the surgeon. They may help to improve surgical and therapeutic techniques. Certain patterns may prove to be characteristic of physiological or pathological conditions, in which case meridional profiles may have use as a diagnostic tool. PMID- 1293537 TI - Analysis of refractive status of Hong Kong Chinese infants. AB - Recently developed methods of quantifying changing dioptric power are applied to the refractive status of Hong Kong Chinese infants from about 10 to about 40 weeks of age. The analysis confirms that hyperopia decreases during the period and that with-the-rule astigmatism predominates. Change, however, is not constant over the period. The rate of decrease of hyperopia slows down and the refractive status becomes more spherical. The mean refractive status is calculated at 10, 20, 30 and 40 weeks. The spread of refractive status is represented by variance covariance matrices calculated for each group and 95% confidence ellipsoids on the mean are constructed. The variance-covariance exhibits little change over the period. The right and left eyes show similar behaviour. PMID- 1293538 TI - Strategy for the design of multifocal surfaces. AB - A method is proposed which may prove useful as an aid in the design of non spherical surfaces with desired multifocal properties. More specifically, if an axially symmetrical surface is described by a polynomial then the coefficients of this polynomial can be found such that optical path lengths between given object and image points are nearly constant over desired portions of the surface. Three examples are given. One of the examples, a 'trifocal' surface, is compared to an aberration-free two-segment concentric bifocal contact lens. PMID- 1293539 TI - Construction of a model eye and its applications. AB - Construction details are given of a model eye, based on the Bennett and Rabbetts schematic eye. It incorporates a cornea, lens, and spherical fundus. Distilled water filled the anterior and vitreous chambers. By means of a micrometer screw, the vitreous chamber depth can be precisely varied to produce axial ametropia from +11 to -17 D. Readings taken over the greater part of this range with a Topcon Autorefractor RM-A6500 were found to be repeatable and reproducible within +/- 0.25 D. The model eye was used to investigate the relationship between the actual size of a fundus feature and its photographic image in two different fundus cameras. With a Zeiss Oberkochen camera of telecentric design the magnification was found to remain constant whatever the degree of axial ametropia, whereas with a Carl Zeiss Jena camera the magnification varied linearly with ametropia. A technique developed by Littmann for determining the actual size of a retinal feature when using a fundus camera of telecentric design is discussed briefly. PMID- 1293540 TI - Effects of different ocular fixation conditions on A-scan ultrasound biometry measurements. AB - A-scan readings must be taken along the visual axis for accurate axial length measurement. Various fixation targets, which ideally should not induce accommodation, are used to limit eye movements. In this study results using the Humphrey biometer under different fixation conditions were compared to establish the most suitable target. We also investigated corneal applanation effects by comparing optical and ultrasonic measurements of anterior chamber depth. We examined 12 randomly selected normal eyes of 12 young subjects. Three A-scans were recorded for each of five fixation conditions: spotlight at 6 m; Snellen letter at 6 m; solid probe's built-in green fixation target; Snellen letter at 6 m viewed through a -4.00 DS lens; spotlight at 6 m under cycloplegia (the comparison condition). Variability 'within' each fixation condition, estimated by the standard deviation for each subject, was equal throughout the 12 subjects for each fixation condition. Also variation was independent of size of the ocular dimension. The good agreement between the comparison condition and optical anterior chamber depth measurements indicated that the solid probe produced little applanation. Differences 'between' fixation conditions were investigated. It was concluded that a spotlight or letter at 6 m provides a suitable fixation target for biometry. Built-in fixation targets can produce significant errors. PMID- 1293541 TI - Capillary filtration in venous hypertension. Comparison between the vacuum suction chamber (VSC) device and straingauge phlethysmography. AB - To evaluate capillary filtration a group of normal subjects and two groups of subjects with venous incompetence (50 with deep and 50 with superficial incompetence) were studied with the vacuum suction chamber (VSC) device applied onto the internal perimalleolar region. This method was compared with straingauge plethysmography rate of ankle swelling (RAS). By the VSC the time taken for the weal to disappear (VSC time) was considered indicative of capillary filtration. The values obtained with the two methods were well related (r < 0.742) and there was a good separation between patients and normals. The separation between the two groups of patients was significantly better (p < 0.05) with the VSC time. In conclusion VSC time is a good indication of capillary filtration in comparison with straingauge plethysmography RAS. It may be used to assess variations in capillary filtration in venous hypertension and possibly to follow up the effects of treatments. PMID- 1293542 TI - Relations between subcellular events in the degenerating notochord and histopathological features of the spinal chordomas. AB - The authors focused their attention on the cytology of the degenerating notochord at the level of the vertebral anlagen and compared it with data of the literature on the histopathology of the spinal chordomas. The purpose of the research was to investigate the notochordal histological features justifying the fact that the remnants of a structure destined to atrophy during prenatal life, maintain a proliferative potential in postnatal life. Therefore, from the earliest stages (24th incubation hour) to the terms of development, the notochord was studied by electron microscope in chick embryo. The data obtained show that, in most notochordal cells, signs of metabolic damage and progressive degeneration coexist with signs of secretory and mitotic activity, from which the proliferative potential of these cells seems to derive. Vacuolar degeneration is also likely due to the progressive metabolic segregation of the notochord, owing to the absence of blood-vessels and the appearance of perichordal sheath. PMID- 1293543 TI - Cholesterol in normal and pathological seminal plasma. AB - One hundred and twenty eight samples (seminal plasma) were studied for cholesterol. They included normozoospermia (44), oligozoospermia (22), oligoasthenozoospermia (34) and azoospermia (28). The cholesterol level in normal group was 61.48 mg/dl (32.5-97.5 mg/dl). Among the groups no difference was seen in cholesterol level. Correlation (r = 10.35) was existing between total spermatozoa count and the level of cholesterol in normozoospermia. A reverse pattern was seen in oligozoospermia (r = -4.04). There was no correlation present between cholesterol and spermatozoa motility in any groups studied. PMID- 1293544 TI - Experimental investigation on histocompatibility of bovine collagen in rat tongue. AB - Authors injected a 1.5-2 cc Gax-Collagen into the tongue of 13 rats in order to examine the reactivity of the tissues around the graft and its attitude and duration. The research had practical purposes as the material is mainly used in E.N.T. for reconstructing the vocal cords. The animals have been sacrificed from 1 day to 9 months and the tongue subjected to the ordinary histologic methods. Our conclusions are as follows: a) a moderate inflammatory reaction following the introduction of the foreign body, then it attenuates and disappears at the third month; b) the implant is well tolerated, does not cause structural alterations in the surrounding tissues, in particular in the musculature where it is placed; c) a neovascularization appears, it lessens over the time, keeping itself only at the edge of the graft; d) in the formed fissures, fibroblasts, traces of collagen and neocollagen are present. All these conditions allow for taking root and the persistence of the implant. It is remarkable that the spherical form of the Gax Collagen does not modify even if it has been implanted into a muscular organ and therefore subjected to severe and continuous mechanical stress. PMID- 1293545 TI - Usefulness of the determination of carcinoembryonic antigen (CEA) in the serum of patients with colorectal cancer in Albania. AB - In our work we have studied the value of the determination of serum CEA in patients with colorectal cancer. We have studied 56 patients with colorectal cancer aged 40 +/- 16 years of both sexes, 26 of whom have metastasis and 30 not. The positivity of serum CEA in the patients with colorectal cancer was 66% (37/56) in the patients without metastasis 53% (16/30) and in the patients with metastasis 80.7%. (21/26). The referent values of serum CEA were significantly lower than the values of serum CEA in the patients with colorectal cancer with and without metastasis (p1 < 0.001). Also we noticed that the values of serum CEA of the patients with colorectal cancer with metastasis were considerably higher than those without metastasis (p2 < 0.001). Analysing the values of serum CEA in the patients with colorectal cancer we noticed that all the patients of our work that had serum CEA value 20 ng/ml had metastasis. Relying on our data we conclude that the determination of serum CEA in the patients with colorectal cancer is very useful for the diagnosis and the prognosis of these patients. PMID- 1293546 TI - Effect of immunostimulating therapy on the immunocompetent system in breast carcinoma. AB - The authors studied 68 patients suffering from breast cancer, with or without lymph node metastasis, who underwent surgery and antitumour therapy (CMF). Twenty three patients were treated using CMF and 1.5 mg/kg of thymostimulin, 24 with CMF and 1 mg/kg of thymostimulin and lastly, 21 subjects received anti-tumour therapy with CMF alone. Thymostimulin was administered every day for a week prior to surgery; subsequently, it was administered on alternate days for a week and then twice a week for 3 months. The blastogenesis of immunocompetent cells was evaluated. During thymostimulin treatment a higher rate of 3HTdR captation (p < 0.005) by cells stimulated with ConA + IL-2 was observed; these levels tended to increase after 3 weeks and reached statistically significant levels after 3 months of treatment; no significant changes were observed in those patients treated with CMF alone. In addition, the cytotoxic activity of monocytes and NK cells against K-562 cells and against short-lasting cell lines derived from breast carcinoma was also studied. It was observed that this activity increased significantly (p < 0.002) following thymostimulin treatment; this increase was greater in subjects treated with 1.5 mg/kg compared to those treated with 1 mg/kg, but the difference was not statistically significant. The study also evaluated the presence of IL-2 receptors (Tac): thymostimulin treatment for 3 months led to the appearance of receptors, although in restricted numbers, on non stimulated cells. After IL-2 stimulation, the percentage of cells with Tac receptors increased significantly (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293547 TI - Surgical approach to combined abdominal aortic aneurysm and renal artery stenosis. AB - Thirty-four cases of combined abdominal aortic aneurysm (AAA) and renal artery stenosis (RAS) are reported. Hypertension was found at admission in 32 subjects, the other two being well responsive to drug therapy. Angiography and selective renal vein renin assay were always performed: renal artery stenosis was unilateral in 21 (61.7%) subjects and bilateral in 13 (38.3%). In 9 cases renal artery stenosis was not correlated to the hypertensive state. Mild chronic renal insufficiency was demonstrated preoperatively in 20 patients (58.8%). Simultaneous surgical treatment was carried out in 25 cases (73.5%). Mortality was 4% (one subject), severe renal insufficiency 8% (two subjects) and permanent renal failure 4% (one subject) All complications occurred among the group with bilateral RAS. While surgical repair of AAA is always mandatory, simultaneous surgical treatment of AAA and RAS should be carried out in carefully selected cases, due to elevated mortality rates reported in the literature, in order to cure renovascular hypertension, when it is demonstrated as related to RAS, or to preserve renal functionality, when RAS is contralateral to a functionally excluded or hypotrophic kidney or it exceeds 80% of the diameter of the artery. PMID- 1293548 TI - Therapeutic effects of pulsed magnetic fields on joint diseases. AB - The present paper describes the effects of pulsed magnetic fields (MF) on diseases of different joints, in chronic as well as acute conditions where the presence of a phlogistic process is the rule. Optimal parameters for MF applications were sought at the beginning of the study and then applied for 11 years; a technical modification in the MF generator was introduced 5 years ago to satisfy the requirement of a hypothesis advanced to understand the mechanism of MF treatment. 3,014 patients were treated by means of MF at extremely low frequencies and intensities. Patient follow-up was pursued as constantly as possible. Pain removal, recovery of joint mobility and maintenance of the improved conditions represented the parameters for judging the results as good or poor. The chi-square test was applied in order to evaluate the probability that the results are not casual. A general average value of 78.8% of good results and 21.2% of poor results was obtained. Higher (82%) percentages of good results were observed when single joint diseases were considered with respect to multiple joint diseases (polyarthrosis); in the latter, the percentage of good results was definitely lower (66%). The high percentage of good results obtained and the absolute absence of both negative results and undesired side-effects, together with the therapeutic advantage due to a technical modification in the MF generator, led to the conclusion that magnetic field treatment is an excellent physical therapy in cases of joint diseases. A hypothesis is advanced that external magnetic fields influence transmembrane ionic activity. PMID- 1293549 TI - Persistent pain and personality evaluation. A report of seven multi-operated patients for chronic pain complaints of non malignant origin. AB - The MMPI scores, the PPI and the MPQ of seven multi-operated patients for chronic pain complaints of non malignant origin were studied. The results of the analysis performed in this group of surgically treated patients point out that there is a strong evidence of relationship between personality traits and the persistence of pain. PMID- 1293550 TI - Emotional characteristics of chronic and acute incestuous daughters. AB - Incest can have a devastating effect on the emotional stability of the victim both in childhood and in adulthood. The present research was conducted to determine: (1) emotional variables associated with chronic and acute incestuous daughters, and (2) a comparison of the similarities and/or differences of each. Results suggested ten different variables of importance in father-daughter incest, however, there were significant differences regarding which of these tended to be associated more with either the chronic or acute incestuous daughters. PMID- 1293551 TI - Combined adrenal adenoma and myelolipoma in a patient with Conn syndrome. Case report. AB - Adrenal myelolipoma is an uncommon benign tumor usually discovered by chance in patients with hypertension, obesity, arteriosclerosis or cancer. The association with adrenocortical endocrine dysfunctions is rare. We report herein an unusual case, the second in the literature to the best of our knowledge, of combined adrenal adenoma and myelolipoma in a patient with Conn syndrome. PMID- 1293552 TI - Group modalities in the care of clients with drug and alcohol problems. PMID- 1293553 TI - Research perspectives on alcohol and drug problems. PMID- 1293554 TI - The role of the nurse on the interdisciplinary treatment team. PMID- 1293555 TI - Impaired professional practice: management issues. PMID- 1293556 TI - Perspectives on drug and alcohol problems. PMID- 1293557 TI - Nursing strategies with the client with alcohol and drug problems. PMID- 1293558 TI - Patterns of addiction in the family. PMID- 1293559 TI - Nursing strategies with alcohol and drug problems in the family. PMID- 1293560 TI - [Prevalence of HIV antigens in cerebrospinal fluid and in serum of patients with both asymptomatic and symptomatic HIV infection]. AB - Prevalence of HIV-Ag in both serum and CSF has been determined in 19 HIV infected patients, including 7 patients without any symptoms or only generalized lymphadenopathy, 5 patients with ARC and 7 patients with AIDS. The results have been correlated with clinically evident neurological disorders. HIV-Ag have been detected in 9 out of 12 patients with ARC (AIDS Related Complex) and AIDS. In 8 of them neurological disorders have been present. Out of the remaining 7 patients in only one HIV-Ag has been detected in CSF (p < 025). No correlation between the presence of HIV antigen in CSF and serum has been noted. PMID- 1293561 TI - [Quantitative assay of CD8+ (cytotoxic and suppressor) lymphocytes in patients with both asymptomatic and symptomatic HIV infection]. AB - Lymphocytes CD8+ have been assayed prospectively in 245 individuals infected with HIV. Percentage and number of CD8+ have been nearly two-fold higher in asymptomatic patients or patients with lymphadenopathy than those in the control group. The number of CD8+ lymphocytes has been rapidly decreasing parallel to the progression of HIV (ARC and AIDS), while their percentage has increased--however insignificantly. There has been a positive correlation between the number of CD4+ and CD8+ cells and all clinical stages of HIV infection. PMID- 1293562 TI - [Affinity of antibody anti-HBs in patients after asymptomatic or symptomatic infection with hepatitis B virus and in individuals vaccinated against this virus]. PMID- 1293563 TI - [Tuberculosis of the lymphatic nodes and coexisting invasion with Toxoplasma gondii]. AB - Six cases of the peripheral lymphatic nodes tuberculosis with positive serologic reactions to Toxoplasma gondii antigen are presented. It was shown, that independently of a complex of clinical examinations histologic examination is decisive for the diagnosis of lymphatic nodes tuberculosis with coexisting toxoplasmosis. A positive serologic reaction with T. gondii antigen in patients with lymphatic nodes tuberculosis may reflect inactive infection with T. gondii. Use of anti-toxoplasmosis drugs may be not necessary in such cases. PMID- 1293564 TI - [Epidemiologic and clinical aspects of leptospirosis with reference to personal observations]. PMID- 1293565 TI - [Incubation period of varicella in children with neoplastic diseases]. AB - Duration of varicella incubation period has been analysed in 21 pediatric patients with neoplastic diseases and in 59 children without immunological deficiency. In has been found, that incubation period has been significantly longer in children with neoplastic diseases (mean 19.58 days), than that in children without immunologic disorders (15.45 days). The difference was statistically significant (p < 0.001). PMID- 1293566 TI - [Effect of ethylenediaminetetraacetic acid disodium salt and doxycycline on drug resistant bacteria]. AB - Effect of Na2EDTA and doxycycline applied alone and in combination in the treatment of experimentally induced dermatitis in rabbits with Staphylococcus aureus resistant to tetracyclines was studied. The rabbits were divided into three groups. The animals of group I were treated locally with the ointment containing 1% doxycycline or 1% Na2EDTA. In group II topical treatment was applied by means of injections of Na2EDTA solution in doses of 12.5 and 6.25 mg Na2EDTA per 1 kg/body weight. Group III was also treated locally with Na2EDTA solution like in group II, but additionally doxycycline in a dose of 50 micrograms per 1 kg/body weight was given i.v. Favourable therapeutic results were observed in the case of local, simultaneous application of Na2EDTA and doxycycline, or local application of Na2EDTA, and intravenous administration of doxycycline. However, the best therapeutic effect was seen in the case of local, simultaneous application of the ointment containing Na2EDTA and doxycycline. PMID- 1293567 TI - [Evaluation of diagnostic methods in the early recognition of toxoplasmosis in children]. PMID- 1293569 TI - [Late episodes of apnea in a premature infant infected with E. coli O111K58]. AB - Typical episodes of apnoea with paleness and cyanosis have been noted noted in premature baby born on the 28th week of pregnancy with body weight 1,010 g as a result of infection with enteropathogenic strain of E. coli O111K58 on the 21st day of life (3rd day of the infection). Effective treatment with antibiotics produced recovery. PMID- 1293568 TI - [Sarcoidosis in coexistence with Toxoplasma gondii invasion]. AB - Two cases of sarcoidosis with peripheral lymphatic nodes involvement and coexisting toxoplasmosis are presented. Both cases illustrate diagnostic and differentiating problems in patients with chronic lymphatic nodes enlargement and positive serological reaction to T. gondii antigen. An emphasis is on the importance of the histological examination of the lymphatic nodes for the sarcoidosis diagnosis and contribution of T. gondii to the disease. Positive serological reaction to T. gondii antigen in patients with sarcoidosis may reflect inactive toxoplasmosis; however, periodical serological tests are necessary monitoring the due immunosuppressive treatment used in patients with sarcoidosis. PMID- 1293570 TI - [A new case of cutaneous myiasis from South America via the larva Dermatobia hominis (L. Jr.)]. AB - A case of cutaneous myiasis produced by D. hominis in a 26-year Polish missionary, who spent 3 months in Peru in 1990 is presented. Practical indications helpful in the diagnosis of this parasitosis are given together with data concerning occurrence and biology of D. hominis. PMID- 1293572 TI - Child sexual abuse. PMID- 1293571 TI - [Aspergillosis of the lymphatic nodes]. AB - The authors emphasize fungal lesions to the lymphatic nodes confirmed by the presence of Aspergillus flavus in blood and throat smear cultures (on Sabouraud's medium) and presence of A. flavus in cytological examination of biopsy from the lymphatic node, increased number of eosinophils in peripheral blood, and infiltration of eosinophils in bone marrow and lymphatic nodes. Aspergillosis coexisted with the infection with Candida albicans and S. aureus. The treatment of recurrent tonsillitis with antibiotics and also lowered granulocyte myeloperoxidase activity with increased production of O2 peroxide ion might predispose to such fungal infection. PMID- 1293573 TI - Failure to thrive/growth deficiency. PMID- 1293574 TI - Lead poisoning. PMID- 1293575 TI - Index of suspicion. Case 2. Diagnosis: autoimmune hemolytic anemia. PMID- 1293576 TI - Index of suspicion. Case 3. Diagnosis: prolonged QT interval. PMID- 1293577 TI - [Professor Jerzy Gieldanowski]. PMID- 1293578 TI - [Antibodies labelled with dyes their application in diagnosis]. AB - Antibodies labelled with some disperse dyes, colored polymers, fluoro- and chemiluminescence, formazan, colloidal gold and selenium are reviewed. An application of the labelled antibodies in commercially available diagnostic home tests is presented. PMID- 1293579 TI - [Aerobic actinomycetes and their significance in human and animal pathology. I. Actinomycetales infections--characteristics, etiology, epidemiology and pathogenesis]. AB - Aerobic actinomycetes causing nocardiosis, GRT-(Gordona, Rhodococcus, Tsukamurella) infections, actinomycetomas, dermatophilosis and extrinsic allergic alveolitis, including etiology, epidemiology and pathogenesis of the diseases are described. The name "actinomycetosis" for all these diseases has been proposed. Many clinical important and potential pathogens, as well as an increasing number of opportunistic, immunosuppressed and immunocompromised cases are discussed. A review of the abundant literature up to date, concerning the problem, is presented. PMID- 1293580 TI - [Targeted immunotherapy against interleukin 2 receptors (IL-2R)--an attempt at synthesis]. PMID- 1293581 TI - [Regulation of immunoglobulin class E synthesis]. AB - IgE production by B cell is T cell dependent. Induction of human IgE synthesis requires IL-4 and T/B cell physical interactions. The pivotal role of cytokines and of Fc epsilon R2 and its soluble fragments in regulation of IgE synthesis are presented. PMID- 1293582 TI - [Dna adducts--characterization and role in chemical carcinogenesis]. AB - A review of the metabolic pathways and interaction with DNA of benzo[a]pyrene and some other carcinogens is presented. Consideration is given to the formation and persistence of adducts in relation to carcinogenic process. PMID- 1293583 TI - [Role of blood platelets in pathogenesis of ischemic cerebral infarction]. AB - The author considers the role of platelet reaction as adhesion, release, and aggregation in the development of ischaemic stroke. The special attention is paid to the problem of platelet behaviour in stroke victims and the role of platelet activity in brain infarction in the young. PMID- 1293584 TI - [Mechanism and kinetics of micronuclei formation in mouse bone marrow]. AB - The paper presents a review of results concerning mechanism and kinetics of micronuclei formation. Special attention has been paid to differences in the induction of micronuclei by clastogenic compounds and spindle poisons as well as modifying factors which play important role in micronuclei formation. PMID- 1293585 TI - [Advances in haptoglobin research]. PMID- 1293586 TI - [Glucocorticosteroid receptors--experimental and clinical aspects]. PMID- 1293587 TI - [The role of iron in immunologic processes]. AB - Iron, apart a for long time well-known function connected with: transportation (hemoglobin), storage (myoglobin), and utilize (cytochromes, cytochrome oxidase) oxygen for respiration, has a critical role in host-pathogen interactions. Iron is essential for microbial growth, but also for immune function. The role of iron in infection, thermoregulation, acute lymphocytic leukemia, neoplasia, rheumatoid arthritis, stimulation of free radical reactions, and studies with iron chelation therapy are discussed. PMID- 1293588 TI - [Alcohol dehydrogenase--polymorphism, properties and role in ethanol metabolism]. AB - The paper presents the molecular and kinetics aspects of alcohol dehydrogenase polymorphism. The role of this enzyme in ethanol metabolism are too discussed. PMID- 1293589 TI - [Interaction of acetaldehyde and proteins]. AB - A review of literature dealing with acetaldehyde-proteins reactions in vitro and in vivo was done. The changes in proteins structure and functions resulting from acetaldehyde binding were discussed. PMID- 1293590 TI - [Acute poisoning with trichloroethylene, toluene and xylene--toxicokinetic mathematical models and clinical experiments]. AB - The paper presents a review of toxic activity of three solvents and mathematical models of their metabolism and different routes of elimination. Special attention was paid to clinical difficulties and complications which may occur during acute poisonings, especially the immunological disorders and coagulation disturbances. PMID- 1293592 TI - [Boleslaw Skarzynski 1901-1963. Recipient of the Polish Biochemical Society award for the best article published in the quarterly Biochemical Progress]. PMID- 1293593 TI - [Wlodzimierz Mozolowski 1895-1975. Recipient of the PTBioch award for a young biochemist for the best and the best represented bulletin at the annual Society Assembly]. PMID- 1293594 TI - [RNA editing]. PMID- 1293591 TI - [Jakub Karol Parnas 1884-1949. Recipient of the award from the Polish Biochemical Society for the best executed research in the country in the field of biochemistry]. PMID- 1293595 TI - [The introns of group I and II, satellite RNAs of plant viruses, viroids ant tRNA like structures as chosen examples for considering the role of RNA in the evolution of the present day genetic system]. PMID- 1293597 TI - [The role of protein C in coagulation and fibrinolysis]. PMID- 1293596 TI - [Functional reliance of nucleic acids on structure]. PMID- 1293598 TI - [Value of ethology in psychiatry]. PMID- 1293599 TI - [Effect of atropine therapy on sudden infant death. A multicenter survey of 7851 children at risk]. AB - The results of a multicentre inquiry started in 1988 in reference centres of sudden infant death are presented. This study concerns the sudden and unexplained mortality of infants under 1 year of age who were treated with atropinics for an alleged risk of sudden death. The 7,851 infants involved were divided into 2,605 siblings, 1,067 premature babies and 4,179 infants who experienced malaises. Only one of the 2,034 infants treated with atropinics (385 siblings, 435 prematures, 1,214 with malaise) died, as opposed to 27 deaths among the 5,817 infants who where not treated (10 deaths among 2,220 siblings, 6 among 632 premature and 11 among 2,965 infants with malaise); P = 0.005. These results are encouraging, but they suffer from the limitations and biases inherent in all large inquiries. They certainly do not allow us to conclude without reservation that vagal hyperreflectivity is the mechanism responsible for sudden infant death and that atropinics must be systematically given to all infants at risk. Wide and randomized prospective studies are highly desirable in this particular field. PMID- 1293600 TI - [Hepatobiliary manifestations in AIDS in adults. Place of cholecystectomy]. AB - In AIDS patients an acalculous cholecystitis may be responsible for abdominal pain subsiding after cholecystectomy. But the indications for cholecystectomy are not clear: cholecystitis is usually associated with diffuse cholangitis and this might cause the symptoms. Since 1985, 8 AIDS patients have undergone cholecystectomy for acute cholecystitis. Ultrasonography revealed a 5 to 12 mm thickening of the gallbladder wall in all of them and gallbladder stones in two; four patients had cholangitis. The decision to operate was based on persistent pain associated with fever, poor general condition and muscular rigidity at palpation. Four patients had septic shock at the time of surgery; one died in the immediate postoperative period. In all other patients pain and septic syndrome subsided. Two patients died of AIDS complications 20 days after surgery; the remaining five died of AIDS 6, 9, 10, 12 and 14 months respectively after surgery; in two of them cholestasis had reappeared due to cholangitis. To summarize, in the 8 AIDS patients studied cholecystectomy was performed for clinical deterioration. Gallbladder pathology was responsible for the abdominal pain and the febrile general condition which was relieved by cholecystectomy. PMID- 1293601 TI - [Neuroendocrine tumor of the trachea of the intermediate type. Value of its individualization]. AB - Tracheobronchial neuroendocrine tumours can be divided into 4 main groups: typical carcinoid; well-differentiated neuroendocrine carcinoma (atypical carcinoid); neuroendocrine carcinoma of the intermediate type, and small-cell carcinoma. Typical and atypical carcinoids are differentiated tumours, whereas intermediate neuroendocrine tumours and small cell carcinomas are little or not differentiated. Morphological or architectural criteria usually suffice to distinguish between carcinoid tumours and small cell carcinomas. In some cases, however, the neuroendocrine nature of poorly differentiated and non-small cell carcinomas is suggested by morphological criteria, but it can be confirmed only by immunohistochemistry and electron microscopy. Tracheobronchial neuroendocrine tumours of the intermediate type have been studied from a first, well-documented clinical case which demonstrated two important points: the prognosis of these tumours seems to be worse than that of carcinoid tumours, and they favourably respond to chemotherapy. In view of the therapeutic consequences, it is necessary to investigate, by the appropriate techniques, the neuroendocrine nature of these poorly differentiated carcinomas. PMID- 1293602 TI - [Fetal toxicity of non-steroidal anti-inflammatory agents]. AB - All non-steroidal anti-inflammatory drugs (NSAIDs) are prostaglandin inhibitors, which explains their foetal toxicity. So far, no epidemiological study of their cardiopulmonary and renal effects has been carried out, but case-reports have been published. The cardiopulmonary effects of NSAIDs include closure of the ductus arteriosus, pulmonary hypertension cardiopathy and tricuspid valve insufficiency. They were responsible for 31 neonatal accidents, 8 of which were fatal (for 22 pregnant women, 7 bearing twins, 1 bearing triplets). The renal effects of NSAIDs consisted of acute renal failure with oedema, oliguria, hyponatraemia and marked hyperkalaemia. They affected 23 neonates, 8 of whom died (for 17 pregnant women, 4 bearing twins, 1 bearing triplets). A few epidemiological studies have reported foetal haemorrhages when aspirin was used by the mother as anti-inflammatory agent. In comparative trials of indomethacin as short treatment of premature labour and polyhydramnios the drug proved to be effective. In obstetrical tocolysis NSAIDs can be given in the absence of alternative therapy with beta-adrenergic agents, and their risk can be minimized by ultrasonographic examination and monitoring of foetal cardiac function and diuresis. In the field of rheumatology, corticosteroids would be a good alternative to NSAIDs for rheumatic diseases, but using NSAIDs for low back pain, sciatica, haemorrhoids, toothaches, sinusitis, etc., would not be justified in pregnant women. Self medication must be discouraged. PMID- 1293604 TI - [A surprise of surgical celioscopy]. PMID- 1293603 TI - [Important prevalence of type 2 diabetes mellitus in dialysed uremic patients in French departments and overseas territories]. PMID- 1293605 TI - [Primary glomerular nephropathies in southern Tunisia]. PMID- 1293606 TI - [Drug-induced serum sickness after ingestion of cefatrizine. First reported case]. PMID- 1293607 TI - [Otorhinolaryngologic localization of malignant lymphomas associated with HIV infection. A new factor in erroneous prognosis?]. PMID- 1293608 TI - [Pubic pain revealing postoperative pubic osteitis]. PMID- 1293609 TI - [Thrombolysed myocardial infarction complicated by cardiac insufficiency. Cost and quality of life]. PMID- 1293610 TI - [Ambulatory isotopic monitoring of left ventricular ejection fraction. Preliminary results]. PMID- 1293611 TI - [Reactions of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with amines]. AB - The reaction of the title compounds with amines gave in dependence of the reaction conditions and the structure of the title compounds and the amine 3 acylamino-thieno[2,3-b]pyridine-2-carbonamides (B), 4-oxo-4 H pyrido[3',2':4,5]thieno[3,2-d]pyrimidines (D),N-(2-carboxy-thieno[2,3-b]pyridine 3-yl)amidines (C) and N-(thieno[2,3-b]pyridin-3-yl)amidines (E). Substances of structure C and E seem to be of biological interest, especially for their antianaphylactic reactions. PMID- 1293612 TI - MAOI activity of some novel series of substituted thiazol-2-yl-hydrazines. AB - Three series of 2-thiazolylhydrazines were synthetized and evaluated for their MAO inhibitory (MAOI) activity, both by in vivo tests, to assay their influence on several MAOI activity-related parameters (the variation on blood pressure induced by tyramine and clonidine and L-amfetamine-induced hypermotility) and in vitro tests, to assay their effect on rat brain mitochondria by a kinuramine fluorimetric assay. In vivo, all the tested compounds significatively influenced the evaluative parameters used. As regards in vitro test, all compounds displayed MAOI activity at a concentration of 1.10(-4) mol.l-1, which was significant in several cases. In the discussion of the results, the influence of the structure on the biological activity of the prepared compounds was delineated. PMID- 1293613 TI - [Antiarrhythmic active amidinohydrazones of substituted benzophenones. 3. The isomerization of (E)-2-amino-5-chlorobenzophenone amidinohydrazones]. AB - The isomerization of the title compound in a preparative scale can be realized by acetylation/deacetylation or by influence of protons in dimethylformamide. The title compound is obtained als main product of the condensation of 2-amino-5 chlorbenzophenone and aminoguanidine if the reaction is carried out in the presence of formaldehyde. PMID- 1293615 TI - [Antiarrhythmic active amidinohydrazones of substituted benzophenones. 4. The photoisomerization of (Z)- and (E)-2-amino-5-chlorobenzophenone amidinohydrazones and the corresponding (E)-N-phenylamidinohydrazone]. AB - The title compounds undergo a photoisomerization by irradiation. If the E-isomers are irradiated by light of a wavelength of an absorption maximum typical for them, they can be converted quantitatively to the corresponding Z-isomers. In case that the synthesis of analogs of the title compounds give only one configurational isomer, sometimes the missing one can be obtained by photoisomerization. PMID- 1293614 TI - [Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)amidines by means of reaction of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with primary aliphatic amines]. AB - The title compounds were synthesized by the reaction of tricyclic compounds of structure B with primary aliphatic amines under different conditions and useful isolation methods in good yields. These compounds showed an acceptable antianaphylactic activity. PMID- 1293616 TI - Development of medicated aerosol dressings of chlorhexidine acetate with hemostatics. AB - Aerosol formulations to act as medicated aerosol dressings have been prepared with an aim of forming a protective film over the wound after spraying combining the properties of antiseptics and hemostatics. Chlorhexidine acetate along with three hemostatics namely zinc acetate, methyl cellulose and Calendula tincture were used for the formulations. The formulations were found to be satisfactory in their performance and purpose. PMID- 1293617 TI - [The effect of cholesterol on membrane potentials, proliferation and migration of cultivated endothelial cells]. AB - The influence of cholesterol added as cholesterol containing liposomes [sphingomyelin/cholesterol (1: 1; mol/mol)] or as cholesterol suspensions on cultured bovine aortic endothelial cells was investigated. 10(-6) mol/l cholesterol enhanced membrane potential, 10(-5) mol/l caused depolarisation. The proliferation of the cells was dependent on the concentration influenced in opposite directions too. The proliferation was stimulated by 10(-6) mol/l cholesterol and inhibited by 10(-5) mol/l. The migratory rate of the cells was increased by 10(-6) mol/l and 10(-5) mol/l cholesterol. Our results suggest that exogenous cholesterol is integrated in membranes of the endothelial cells and causes in this way changes of membrane potential, proliferation rate and migratory activity. PMID- 1293618 TI - [The development of pharmaceutical analysis at German universities in the 19th and 20th century]. AB - The aim of this paper is to trace some features of the historical development of drug analysis as an academic discipline in its relation to the emergence of pharmaceutical science. In the first half of the nineteenth century pharmacists identified and characterized minerals, plants and drugs. K.F. Mohr played a decisive part in the founding of the new discipline drug analysis. The development described here, which began in Marburg, Breslau and Konigsberg and was extended to other places, led to the evolution of drug analysis. The establishing of independent departments, for instance in the former G.D.R., played a decisive role in developing the discipline drug analysis. PMID- 1293619 TI - Effect of PEG 400, ethanol and laurocapram (Azone) on the transport of testosterone through rat skin. PMID- 1293620 TI - The reproductive revolution: new survey findings. AB - A reproductive revolution is spreading across much of the developing world. Use of effective contraception has risen rapidly, and fertility has been falling. But there is still a long way to go. More than one woman in every five wants to avoid pregnancy but is not using contraception. PMID- 1293621 TI - Is stupor by itself a catatonic symptom? AB - Many patients present with stupor or substupor without classical catatonic signs as described by Kahlbaum. The phenomenological literature is not clear as to whether stupor, when it presents alone, constitutes a separate syndrome or is a forme fruste of catatonia. All patients who presented with stupor, (a) partial or total mutism or (b) absent or decreased motor responses (n = 22), were compared with patients who also had classical catatonic signs such as negativism or waxy flexibility (n = 43) over a one-year period (1988), on sociodemographic and clinical variables. There were very few significant differences between the two groups (age, sex, diagnosis, duration of illness, number of ECTs required). The stupor group had a slight excess of patients with manic-depressive psychosis, depression and more frequently positive family histories of mental illness. The current study provides a tentative support to the hypothesis that stupor is a catatonic sign, and even when present alone can be considered to constitute a catatonic syndrome. PMID- 1293622 TI - A polydiagnostic approach to self-perceived cognitive disorders in schizophrenia. AB - The relationship between the self-perceived cognitive disorders (SPCD) assessed using the Frankfurt Complaint Questionnaire (FCQ) and 21 definitions of schizophrenia was studied in a sample of 118 consecutively admitted patients. The FCQ total score was significantly associated (p < 0.05) with the presence of Schneider's, Yusin's and Present State Examination criteria of schizophrenia. A significant association, in this case negative, was also found between the FCQ total score and the presence of the DSM-III-R criteria of schizophrenia. The results suggest that the SPCDs are more associated with Schneider-related criteria than with chronic or deficit models of schizophrenia. It was also found that the female sex as well as the presence of insight were significantly associated with a greater number of SPCDs. PMID- 1293623 TI - On the distinctions between diagnosis, description and measurement of schizophrenia. AB - The distinctions between diagnostic classification of schizophrenia, the description of the characteristics and course of schizophrenia, and measurement of its severity are discussed. There is confusion among these three categories by both researchers and clinicians. The causes for this confusion are discussed, and it is noted that there are few appropriate measures of cognitive function in schizophrenics. It is proposed that the research design used in most schizophrenia research does not lend itself to the development of more informative interval scales. It is proposed that rather than using performance as a dependent measure with a task of fixed level of difficulty, a 'threshold design' should be used, where the environmental factors are varied to produce a given performance level. PMID- 1293624 TI - Exploration of obsessive compulsive phenomena: a preliminary investigation. AB - Different dimensions of obsessions and compulsions were explored in 103 obsessions and 60 compulsions recorded from 32 subjects who received a primary diagnosis of obsessive compulsive disorder. Intrusiveness and repetitiveness formed relatively discrete dimensions, while resistance, distress, irrationality, interference and ease of dismissal tended to be associated within themselves. An anxiety-provoking effect was an additional dimension observed among compulsions. PMID- 1293625 TI - Suicide in the Nordic countries. AB - There are great differences in the suicide rates in the closely related Nordic countries. The suicide rates are higher in Finland, especially in males, and Denmark, especially in females, and lower in Norway and Iceland, with Sweden in a middle position. The statistics are found to be comparable. In this article the development from 1880 to the present day is described, and special emphasis is laid on the development from 1960 onwards. Denmark and Finland still keep the top position, while the rise in suicide rates, especially in the age group 15-29 years, has been most marked in Norway. Within the Nordic region Greenland has an extremely high suicide rate, especially in youngsters, while the Faroe islands have a very low rate. Tentative explanations are given for the development of suicide rates in the Nordic countries. PMID- 1293626 TI - Music psychopathology. V. Objective features of instrumental performance and psychopathology. AB - Mental disease systematically impairs musical expression according to nosologic classification. This was demonstrated with a polarity profile of the instrumental performances of 60 inpatients and 14 controls matched for musical aptitude. Objective performance characteristics such as irregularities and playing faults were analyzed too. No meaningful correlation between these features and psychopathology resulted. This indicates that even in severe psychopathologic alterations performance features, which depend mainly on education and actual training, are not altered in a systematic manner, in contrast to expressive qualities. PMID- 1293627 TI - Music psychopathology. VI. The course objective instrumental performance characteristics with psychiatric inpatients. AB - The impairment of musical expression due to mental disease is reversible with growing remission. This finding resulted from follow-up examinations of instrumental playings assessed by means of a polarity profile with 60 psychiatric inpatients and 14 controls. A follow-up comparison of objective performance characteristics as defined by careful analysis of the recordings did not reveal a meaningful variation. This is taken as a strong indication that even in severe psychopathologic alterations, learned motor patterns of music performance are fairly stable. A simple reduction in playing irregularities cannot explain the systematic influence of psychopathology on musical expression. PMID- 1293628 TI - Checkers and washers: valid subtypes of obsessive compulsive disorder. AB - The current study aimed to examine sociodemographic and clinical variables between washer and checker subgroups of obsessive compulsive disorder. Of 412 subjects seen during 1975-1984, there were 123 washers, 70 checkers and 89 washers and checkers (mixed group). Checkers were more likely to be single and male and have an earlier age of onset and consultation; if married the illness was more likely to have started prior to marriage. The mixed group appeared to be a female-dominated pathoplastic variant of the checkers group. The current study suggests that other variables should also be explored in differentiating these disorders. PMID- 1293629 TI - Trichotillomania. Two case reports from a similar cultural background. AB - Case reports of 2 female patients from the Makrani culture are presented. They were both around 30 years of age, clinically depressed and responded favorably to antidepressants. One of these patients was infertile, and the other one had started pulling her hair when deprived of her jewelry. Fertility and possession of jewelry represent femininity in the Makrani culture. A brief review of the literature on trichotillomania and its psychopathology is also included. PMID- 1293630 TI - Differentiation of DSM-III-R anxiety disorders by severity of illness and symptom onset sequences. AB - 187 patients were investigated by a structured interview for DSM-III-R and various clinicians' and patients' ratings. A high frequency of comorbidity between different anxiety disorders and between anxiety and depression was found. According to sociodemographic data, various anxiety disorders showed more similarities than differences. Patients with a generalized anxiety disorder showed an earlier age at onset compared to patients with panic disorder as well as a greater severity of illness and comorbidity. Avoidance behavior occurred before, simultaneous with, as well as after the onset of panic disorder. PMID- 1293631 TI - Obsessive-compulsive disorder in adolescence. Differential diagnostic considerations in relation to schizophrenia and manic-depressive disorder: a comparison of phenomenology and sociodemographic characteristics. AB - Some borderline cases of obsessive-compulsive disorder (OCD), schizophrenia, and manic-depressive disorder in whom the diagnosis had been difficult to assess in adolescence are presented. The records of 27 OCD patients with admission both in adolescence and adulthood were compared to a group of manic-depressive and schizophrenic patients with an admission in adolescence where the OCD diagnosis had been given. Some differential diagnostic considerations and difficulties in the borderline area between OCD, manic-depressive psychosis and schizophrenia at the time of the first manifestation in adolescence are described. The symptomatology in the three groups of patients as it was presented in adolescence only showed a few differences, and the patients offered differential diagnostic difficulties to the clinicians. PMID- 1293632 TI - A typology of alcoholism in Taiwan aborigines: a study on evolving process of community cases. AB - Thirty-one habitual drinkers with a personal, familial, social complication were screened from a Taiwan aborigine community. Each was given an in-depth descriptive semistructured interview. The interview, recorded with audiotape, contained 4 aspects: (1) personal developmental history; (2) family structure and interaction; (3) developmental process and current state of drinking behavior, and (4) attitude toward drinking behavior. Based on the evolving process and current state of drinking behavior, three process patterns of alcoholism were defined: (1) social developmental type (67.7%); (2) deviant behavioral type (9.7%), and (3) special constitutional type (22.6%). PMID- 1293633 TI - Assessment of saccadic eye movements as an instrument of differential diagnostic screening. AB - Fast conjugate (saccadic) eye movements tested for stimuli between 5 and 30 degrees to the left or the right are characterized by three parameters: latency, maximum velocity, and accuracy. The recordings of 152 patients, diagnosed by the psychiatrist for depressive and/or organic symptoms, demonstrate different sensitivity of saccadic parameters to instruction, medication, and psychopathology. The parameter maximal velocity appears to be a parameter of psychopathology, but above all also of medication, while the parameter latency appears to be primarily a parameter of psychopathology. Accuracy is the more 'psychological' or 'volitional' parameter. PMID- 1293634 TI - Alexithymia and depression in families with alcoholics. AB - Alexithymia and depression in family members of alcoholics were examined among 48 families. Results were as follows: (1) The prevalence of alexithymia was 47.9% (23 cases), whereas that of depression was only 6.3% (3 cases); (2) no significant correlation between alexithymia and depression was noted; (3) expressiveness and conflict were significantly lower in families with alcoholics than in healthy families without alcoholics, although families with alcoholics do have strong conflicts. The results suggest the possibility that half of them forcefully suppress their conflicts, unconsciously deny the existence of alcoholics, and finally manifest secondary alexithymia. PMID- 1293635 TI - The functional architecture of the acetylcholine nicotinic receptor explored by affinity labelling and site-directed mutagenesis. PMID- 1293636 TI - Structure and dynamics of polypeptides and proteins in lipid membranes. PMID- 1293637 TI - Kinetic analysis of lipid soluble ions and carriers. PMID- 1293638 TI - Integration of pharmacology and toxicology. PMID- 1293639 TI - Occupational epidemiological studies in risk assessment and their relation to animal experimental data. AB - The role of epidemiological and animal experimental studies in the process of qualitative and quantitative risk assessment is discussed. So far little agreement exists between animal experimental data and epidemiological outcomes in the procedure of qualitative risk assessment. Several reasons for these discrepancies are mentioned. The application of existing epidemiological study results in quantitative risk assessment is hampered by factors, such as the lack of exact exposure information (compound, level, duration), undefined other exposures in and outside the working environment, small sample sizes, the comparatively short duration of epidemiological studies and the absence of detailed information about the specific effects. All this resulted in a relatively small impact of epidemiological studies in risk assessment. Recommendations are made in order to improve the impact of epidemiology in risk assessment. PMID- 1293640 TI - Environmental tobacco smoke. AB - In 1992, the U.S. Environmental Protection Agency (EPA) issued a "draft" assessment of ETS and lung cancer in adults and respiratory disorders in children. Relying on weak and inconclusive epidemiological data, the supposed similarity between ETS and MS, the presence of "known or suspected carcinogens" in MS and by extrapolation in ETS, and the "biological plausibility" of an adverse relationship between ETS and health, the EPA recommended that ETS be classified as a "Group A (known human) carcinogen." Fundamental physical and quantitative chemical differences among ETS, MS, and SS and human exposure to each smoke were disregarded: The three are not equivalent nor is ETS exposure a quantitative variant of cigarette smoking. A substantial difference in retention percentage overlays the huge dosimetric difference between exposures. As a result, the "dosage" of ETS retained is miniscule relative to MS. Also, conclusions reached by the EPA and the use of tenuous relationships as bases for Group A classification are unwarranted because of failure to consider the data upon which the "tumorigenicity" of the ETS components was based, questions on the presence and/or levels of these components in MS, and data indicating that a 25- to 30-fold decrease of a high-level dose of MS or MS condensate diminished the effects observed in bioassays from pronounced to zero, i.e., a threshold was demonstrated. Finally, EPA overlooked the more than 100 tobacco smoke components known to inhibit the tumorigenic action of many of the listed "tumorigens." PMID- 1293641 TI - Review of a study reporting an association between 2,4-dichlorophenoxyacetic acid and canine malignant lymphoma: report of an expert panel. PMID- 1293642 TI - Macronutrient substitutes: safety evaluation. AB - Macronutrient substitutes, reduced-calorie substances used to replace organoleptic and/or functional properties of fats and sugars in the diet, may become a significant part of the diet as the trend toward lower fat and lower calorie diets continues. Procedures currently used to evaluate the safety of traditional food additives (microadditives) may be inadequate to properly assess the safety of macronutrient substitutes (macroadditives) because of the unique nature of these substances and the potentially large intakes. An evaluation procedure is proposed that recognizes the benefits to be derived from the test material, uses a structured approach to obtain animal and human nutritional and toxicological (including kinetic and dispositional) data that are critically evaluated and that provide a basis for further testing, encourages consultation with the regulatory agency (FDA), and recommends postmarketing surveillance of the macronutrient substitute. The proposed scheme differs from the traditional approach in many respects, such as using dispositional and kinetic data, assessing nutritional status, using human data collected under carefully controlled conditions early in the process, and consulting with the FDA. A case by-case approach is recommended for safety evaluation of these macroadditives. PMID- 1293643 TI - An assessment of the hazards of lead in food. AB - Exposure to lead (Pb) continues to be a source of concern for the U.S. Food and Drug Administration and other federal regulatory agencies. Blood lead levels as low as 10 micrograms Pb/dl have been associated with impaired neurobehavioral development in children and infants. Because of exposure to the fetus, blood lead levels of 10 micrograms Pb/dl are also of concern in pregnant women. Blood lead levels of 30 micrograms Pb/dl have been associated with elevated blood pressure and other adverse effects in adults. The dietary exposure that results in these blood levels of concern were estimated to be 60 micrograms Pb/day for children age 6 years or younger, 150 micrograms Pb/day for children age 7 years or older, 250 micrograms Pb/day for pregnant women, and 750 micrograms Pb/day for adults. A provisional tolerable total dietary intake was derived by applying a factor of 10 to obtain an exposure level that would include some margin of safety. PMID- 1293644 TI - The Council for Health and Environmental Safety of Soils. AB - The Council for Health and Environmental Safety of Soils (CHESS) was organized in 1987 to develop a consensus soil risk assessment methodology to be used as a framework for establishing standards for soil contamination to protect the environment and public health. The wide range of contaminating substances of possible health concern in soil is affecting land use and development, causing excessive economic expenditures, and the regulatory approaches for control are disperse. The International Society of Regulatory Toxicology and Pharmacology agreed to sponsor the Council and through a Governing Board composed of experienced scientists from the federal government, state departments of public health and environmental protection, academia, and the private sector including industry and environmental organizations. The Board was created to support the goals of CHESS, its mode of operation, and to establish funding policies and directions. A technical council agreed to develop a peer-reviewed consensus methodology to assess public health risks from contaminated soil by technical committees composed of recognized experts in the area of soil contamination and other relevant disciplines. This methodology would then be made available to federal and state agencies, the private sector, and the scientific community at large. After extensive study, a final decision was made to develop a decision tree framework to be used at the state and local levels for application to all types of soil contamination. Following extensive studies it was agreed the ubiquitous nature of petroleum contamination in soil has direct and immediate public health implications and CHESS therefore directed its first efforts to this area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293645 TI - Predicting blood lead concentrations from environmental concentrations. AB - A method is presented by which blood lead concentrations can be estimated from environmental concentrations using a multipathway analysis. For the ingestion and dermal uptake pathways the incremental increase in blood lead concentration is estimated as the product of the concentration in the relevant medium, a medium specific contact rate, and an empirically determined ratio between intake and blood level. The inhalation pathway omits the contact rate and uses a ratio between the concentration in blood and the concentration in air. Model outputs corresponding to various input parameters are presented, and some of these are compared with outputs from the U.S. Environmental Protection Agency's Lead Biokinetic/Uptake model, Lead 5. PMID- 1293646 TI - Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs). AB - The polycyclic aromatic hydrocarbons (PAHs; also referred to as the polynuclear aromatic hydrocarbons or PNAs) are commonly encountered at hazardous waste sites and are often the focus of site remediation activities. However, toxicity criteria are not available for all the PAHs. In the past, EPA has assessed risks posed by mixtures of PAHs by assuming that all carcinogenic PAHs are as potent as benzo[a]pyrene (B[a]P), one of the most potent PAHs. The available information on the toxicity of the PAHs suggests that most are considerably less potent than B[a]P and therefore, the EPA approach is likely to overestimate risks. Several approaches have been developed to allow the relative potency of the different PAHs to be considered in a site-specific risk assessment. This paper evaluates these approaches and presents a modified version that we feel more accurately reflects the state of knowledge on the relative potency of these compounds. PMID- 1293647 TI - Reevaluating the carcinogenicity of ortho-toluidine: a new conclusion and its implications. AB - The aromatic amine ortho-toluidine has been recognized by IARC as an animal carcinogen for the past decade. Three recent epidemiological studies of worker populations have now implicated this chemical as a human bladder carcinogen. In a study by E. Ward, A. Carpenter, S. Markowitz, D. Roberts, and W. Halperin ((1991), J. Natl. Cancer Inst. 83, 501-506), workers definitely exposed to ortho toluidine for at least 10 years experienced a Standardized Incidence Ratio (SIR) of 27.2 (90% CI = 11.8-53.7). The other major exposure was to aniline, which significant epidemiological studies have failed to confirm as a human carcinogen. In retrospect, studies by G. F. Rubino, G. Scansetti, G. Piolatto ((1982) Environ. Res. 27, 241-254) and M. J. Stasik ((1988) Int. Arch. Occup. Environ. Health 60, 21-24) also support the hypothesis that ortho-toluidine is a human bladder carcinogen. Animal studies of both ortho-toluidine and its possible confounders in these epidemiological investigations further confirm this hypothesis. When evaluated in a suitably comprehensive way, according to the traditional standards for assessing causality outlined by A. B. Hill ((1977) A Short Textbook of Medical Statistics, pp. 288-294, Lippincott, Philadelphia) the evidence that ortho-toluidine causes human bladder cancer has become much more conclusive. In this case, animal tests have proven a good predictor of human carcinogenicity. PMID- 1293648 TI - Approaches to evaluating the toxicity and carcinogenicity of man-made fibers: summary of a workshop held November 11-13, 1991, Durham, North Carolina. AB - The Workshop on Approaches to Evaluating the Toxicity and Carcinogenicity of Man Made Fibers (MMF) was held in Durham, North Carolina, on November 11-13, 1991. The goal of the workshop was to reach a consensus, or to determine the extent to which a consensus existed, in two areas. Participants were asked to identify scientifically sound approaches for evaluating the toxicity and carcinogenicity of man-made fibers based on today's science and to determine research appropriate for study during the next 5 years that can provide an improved scientific basis for future revisions of approaches used to evaluate man-made fiber toxicity and carcinogenicity. During the first day, a series of "state of knowledge" presentations were made to provide all participants with a common data base from which to interact and discuss scientific issues. The workshop participants were assigned to one of four discussion groups, which met separately in three half-day sessions following the first day of presentations. All groups discussed the same topics: exposure assessment, hazard identification, and dose-response information needed to integrate to characterize risk in the first session; approaches to obtaining the needed information in the second session; and recommended approaches and guidelines for evaluating the toxicity and carcinogenicity of MMF and research needs in the third session. The workshop participants reconvened as a whole after each discussion session, and one member from each group reported the group's conclusions. A closure period was also included at the end of the workshop for review and discussion of items that had been considered during the workshop. The primary conclusions reached were the following: -All fiber types capable of depositing in the thorax are not alike in their pathogenic potential. Only fiber samples with dimensions similar to those to which humans can inhale should be tested. -A complete characterization (i.e., dimensions, fiber number, mass, and aerodynamic diameter) of the fiber aerosol and retained dose is essential. -Appropriate aerosol generation methods must be used for inhalation studies in order to preserve fiber lengths. -A tiered approach to toxicity evaluation is recommended that includes: 1. In vitro screening for durability, surface properties, cytotoxicity, and similar properties, etc; 2. Short-term inhalation or other in vivo studies; 3. That chronic inhalation studies are the "gold standard" (i.e., provide most appropriate data for risk characterization). The rat is the most appropriate species for inhalation studies. -In chronic inhalation studies, animals should be retained to at least 20% survival after 2 year exposure. -Serial lung burden analyses are an essential component of inhalation studies and are essential for understanding exposure-dose-response relationships. -Studies oriented to understanding mechanisms of toxicity and carcinogenicity are important adjuncts to traditional toxicity studies. Histopathological analyses of tissues of the respiratory tract represent primary endpoints for evaluating effects of inhaled fibers. Major effects include pulmonary fibrosis, lung tumors, and mesotheliomas. Experimental tissues should be archived for future studies; wherever possible, handling and preservation of tissues should be done in a way that maximizes their future use in mechanistic studies. -Potential human exposures throughout the entire life-cycle of the fiber must be considered and fibrous material for toxicologic studies prepared accordingly. -Intracavity studies are inappropriate for risk characterization but can play a useful screening role in assessing fiber toxicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1293649 TI - [Utility of new drugs inhibiting gastric secretion in the prevention of broncho aspiration syndrome during elective surgery]. PMID- 1293650 TI - [Utility of premedication with different regimens of omeprazole and ranitidine in the prevention of acid broncho-aspiration syndrome]. AB - OBJECTIVE: To study the usefulness of several omeprazole regimens on gastric fluid volume and pH in patients undergoing elective surgery. MATERIAL AND METHODS: We analyzed 105 patients undergoing to elective surgery who received prophylactic treatment for the acid aspiration syndrome. They were randomly allocated into 7 homogeneous groups according to the therapeutic regime. Placebo (group 1), oral omeprazole (20 mg) the night prior to surgery (group 2), oral ranitidine (150 mg) the night before (group 6), two doses (the previous night and before surgery) in the remaining three groups: 20 mg of omeprazole (group 4), 40 mg of omeprazole (group 5) or 150 mg of ranitidine (group 7). In all patients we measured pH and volume of the gastric content after induction of anesthesia and one hour thereafter. RESULTS: There were no statistically significant differences in mean pH values and gastric volume content among groups 1.2,3, and 6 (2.1 (pH) and 27 ml (gastric volume) in group 1, 2.1 and 23 ml in group 2, 2.6 and 19 ml in group 3, and 2.2 and 32 ml in group 6). With repeated doses of 40 mg omeprazol (group 5), mean pH values were comparable to those found with the two doses of ranitidine (4.1 +/- 1.8 vs 4.1 +/- 3.6) although gastric volumes were significantly less (12 +/- 2.6 ml vs 20 +/- 4.8 ml). These two groups showed significantly greater mean pH values and less gastric volumes than the remaining patients. CONCLUSIONS: The incidence of patients with gastric content deemed at risk for acid aspiration (pH less than 2.5 and gastric volume greater than 25 ml) was less after premedication with two oral doses of omeprazole (40 mg) than either two doses of ranitidine (150 mg) or smaller doses of both drugs. PMID- 1293651 TI - [Chronotropic changes and cardiac arrhythmias during anesthetic induction and intubation in patients undergoing heart surgery. Study of 79 patients using Holter monitoring]. AB - OBJECTIVES: To assess changes in heart rate and cardiac arrhythmias during anaesthetic induction and tracheal intubation in patients undergoing cardiac surgery. MATERIAL AND METHODS: 79 patients scheduled for cardiac surgery were divided into three groups: group I, 36 valvular diseases with a good ventricular function, group II, 22 valvular diseases with an ejection fraction less than 0.5, and group III, included 21 patients with coronary artery disease. All patients had a Holter monitoring. Anesthesia was performed with diazepam and morphine in patients with valvular disease and with diazepam and fentanyl in those with coronary artery disease. RESULTS: During anesthesia induction there were no significant increases in heart rate in the two groups of patients with valvular diseases: in group I (n = 36, with good ventricular function) heart rate increased by about 5.4 +/- 23% and in group II (n = 22, with ejection fraction less than 0.5) by 7.5 +/- 33%. In patients with coronary artery disease (n = 21) we did not observe significant decreases in heart rate (-4.28 +/- 17%). During tracheal intubation the heart rate increased by 15.9 +/- 30% in group I (p < 0.002), by 13.6 +/- 30% in group II (p < 0.02), but decreased by 1.19 +/- 23% (p = NS) in patients with coronary artery disease. During anesthetic induction we observed frequent premature beats (single forms) in 13.8% of patients in group I, 13.6% in group II, and 9.5% in group III. The incidence of this arrhythmia during tracheal intubation was 16.6%, 9%, and 14%, respectively for the three groups. Sustained ventricular tachycardia was only observed in one patient. CONCLUSIONS: Changes in heart rate and ventricular arrhythmias occurring during anesthetic induction and tracheal intubation in patients undergoing valvular and coronary surgery were infrequent and not severe. PMID- 1293652 TI - [Design of an expert system for decision-making in an emergency situation]. AB - OBJECTIVES: To study the clinical applicability of the expert system URGSANT as a help in making up decisions in emergencies. MATERIAL AND METHODS: URGSANT is an expert system implemented in INSIGT 2+ which is structured in a modular and hierarchical form. It contemplates 44 urgent situations relating to the central nervous system, hematopoietic, cardiovascular, respiratory, gastrointestinal, genitourinary, endocrinological, and miscellaneous group. Validation of the program was made by four anesthesiologists who evaluated the performance of the program in 25 emergency cases and in 25 other situations that were treated by other specialists. RESULTS: The rationale of the system was basically correct. In most cases the program was considered efficient or very efficient during the different clinical situations and only in one case its guidance was wrong. CONCLUSIONS: The URGSANT expert system is an efficient and useful method for the clinician during emergency situations. PMID- 1293653 TI - [Indications for the use of platelets, plasma and anti-hemorrhagic drugs]. AB - During the last years, the use of hemoderivatives has largely increased. Their use carries a high risk for post-transfusion reactions and for transmission of severe infectious diseases. In a high percentage of cases the use of these compounds is inadequate. At the present time there are pharmacologic (desmopressin, antifibrinolytics, vitamin K) and nonpharmacologic strategies (autotransfusion, hemodilution, intra and postoperative recovery of blood) directed to avoid or to decrease the need for transfusion. We review all these strategies and we propose some criteria for transfusion of plasma and platelets, as well as attitudes for particular situations. PMID- 1293654 TI - [Approach to the scientific work of Jaume Raventos (1905-1982)]. AB - We analyze the scientific work done by Jaume Raventos (1905-1982) preceded by a brief biographic profile. The work of this Catalonian investigator has been separated into two stages: The first one, called the Barcelona period, is the training phase and comprises three moments: during the first one (1925-1927) the scientific participation of Raventos is still marginal; during the second period (1928-1933) he began to collaborate in large projects with A. Pi Sunyer and F. Domenech Alsina; and during the third period (1932-1934) he developed its own experimental line that culminated with his Doctoral Thesis. The second stage, called the British period, includes all work done during his exile at the United Kingdom. This phase can also be divided into three periods: the first one (1936 1939) took place in Edinburgh and was characterized by a continuation of the scientific line initiated in Barcelona; the second period developed in Manchester (1939-1954) and includes the studies with intravenous barbiturates; the third period (1956-1965) encompasses the last years of Raventos investigative activity which was devoted to the study of fluothane a new volatile anesthetic agent. PMID- 1293655 TI - [Radial nerve injury caused by external compression during the dissection of the internal mammary artery in coronary surgery]. AB - Injury of the radial nerve produced by external compression during dissection of the internal mammary artery during surgery of ischemic heart disease, is an infrequent event. The use of sternal retractors with only one rod may be the cause of these lesions. We report two cases of radial nerve paralysis produced as a consequence of external compression induced by a sternal retractor during dissection of the internal mammary artery. In the first case the patient showed loss of power of the external muscles of the left forearm and a clear flexion of the left hand. The second patient presented loss of power of the left hand and impossibility to extend the carpus and fingers. In both cases the lesion was reversible. PMID- 1293656 TI - [Inhalation anesthesia in porphyria variegata]. AB - We report the anesthetic technique performed in a 38 year old woman with variegate porphyria who underwent a partial right mastectomy. The patient was diagnosed in 1984 on the basis of the biochemical profile and enzymatic deficit. She presented marked photosensitivity without neurological or systemic symptoms. Among their personal antecedents an uneventful general anesthesia in 1982 was recorded. The patient was premedicated one hour before surgery with 0.25 mg of scopolamine, 5 mg of dihydrobenzperidol (DHB), and 100 micrograms of fentanyl, all of them given by the intramuscular route. At the operating theater the patient received 5 mg of diazepam, 2.5 mg of DHB, and 200 micrograms of fentanyl. Anesthetic induction was done with a bolus of 20 mg of etomidate, 1 mg of atropine, and 60 mg of suxamethonium. Maintenance of the anesthetic level was achieved with 0(2), N2(0) with 0.5 of 1% isoflurane, and 40 mg of atracurium in two doses. Surgery lasted 50 min and pharmacologic reversion of the anesthesia was not required. Urine was collected in a dark recipient 24 hours after surgery in order to measure the following parameters: porphobilinogen, aminolevulinic acid, coproporphyrins and uroporphyrins. We found a significant increase of uroporphyrins at the three sampling times, although this increase was less marked during surgery, probably due to hemodilution. We stress the advantages of inhalation anesthesia in these patients. PMID- 1293657 TI - [Paradoxical reaction to midazolam after its use as a sedative in regional anesthesia]. AB - We report 3 cases of paradoxical reaction to midazolam after being used for sedation during regional anesthesia. The picture was characterized by a marked aggressiveness. In one case the reaction was treated with general anesthesia, whereas in the other two patients the clinical picture was rapidly reversed by administration of flumazenil. We describe the possible causative mechanisms of this reaction as well as their treatment. PMID- 1293658 TI - [Late cardiac tamponade after a penetrating chest wound]. PMID- 1293659 TI - [Oxygen transport and consumption during general anesthesia with enflurane]. PMID- 1293660 TI - [Local anesthesia in Spain in the pre-cocaine era]. PMID- 1293661 TI - [Werlhof's disease: splenectomy. Platelet administration?]. PMID- 1293662 TI - [Usefulness of intravenous patient-controlled analgesia in the treatment of postoperative pain]. PMID- 1293663 TI - [Anesthetic management with propofol in a case of tracheal stenosis]. PMID- 1293664 TI - [Resolution of a case of unforeseen impossible endotracheal intubation by the use of a Brain laryngeal mask]. PMID- 1293665 TI - [Cryoanalgesia in post-thoracotomy pain]. PMID- 1293666 TI - Papers from the International Meetings of the International Society for Clinical Biostatistics. 1989-91. PMID- 1293667 TI - Statistical handling of drop-outs in longitudinal clinical trials. AB - This paper considers the statistical complexities that arise due to outcome related drop-outs in longitudinal clinical trials of the randomized parallel groups design with fixed assessment times and an explanatory aim. The shortcomings of currently popular methods of coping with the problem of drop-outs are discussed. It is proposed that progress can be made by applying the modern methodology that was primarily developed for sample surveys with non-response and for observational studies. A practical application using the Hamilton Rating Scale for Depression is presented. PMID- 1293668 TI - Using toxicity grades in the design and analysis of cancer phase I clinical trials. AB - Ethical considerations in a cancer phase I trial require a design allowing determination of the maximum tolerated dose with a minimum number of patients treated at low ineffectual or high overly toxic doses. It would also be advantageous to complete the phase I trial in as short a period of time and with as few patients as possible to allow further resources for later studies in which patients are treated at the optimal dose. Several dose escalation schemes are compared. These are the Fibonacci, two two-stage schemes, and a proposed scheme which uses knowledge of all toxicity grades. Estimates of the maximum tolerated dose are obtained and compared using the dose escalation schemes alone, a logit model, and a proposed mean response model. Confidence intervals using the delta method are obtained from the logit and mean response models. The proposed scheme and the two-stage schemes have the advantage of requiring fewer patients, particularly at low doses. Confidence intervals obtained from the mean response model have better coverage than those from the logit model. Data from a cancer phase I trial of dipyridamole and acivicin is presented to illustrate the methods. PMID- 1293669 TI - Importance of trends in the interpretation of an overall odds ratio in the meta analysis of clinical trials. AB - This paper contains a proposition related to the publication of meta-analyses of clinical trials. We consider the situation where the results of a number of trials are summarized by a common or typical odds ratio. We show that stating such an odds ratio as the summary of evidence from a number of trials can be misleading if certain systematic differences between trials exist. In such cases the author should state not just one odds ratio but also its dependence on the relevant characteristics of the trials. In particular, we propose that those reporting a meta-analysis state in advance a (limited) number of variables to be considered for potential interaction with the exposure (risk factor or treatment) of interest. The list might include centre size and the odds in the placebo or control group if such an effect is a priori clinically plausible. The trials should be ordered according to each of these variables and a trend test for the odds ratio should be computed. Apart from a 'genuine' effect, an appreciable interaction could also be indicative of the (multiplicative) odds ratio being an inappropriate measure for the particular meta-analysis. Without any consideration as to the possibility of interaction, the meta-analysis should be considered incomplete. If such an interaction exists, the odds ratio should be stated as a function of the interacting variable, either as a formula or (preferably) in a table stating the odds ratio for a number of different values of the interacting variable, and not as a single summary statistic. PMID- 1293670 TI - Comparison of adjusted attributable risk estimators. AB - The estimation of attributable risk in the presence of confounding and effect modification is studied in this paper. Different adjustment methods for the attributable risk are reviewed. The results of a stimulation study comparing these methods under the unrestricted multinomial sampling model are reported. From the study it is concluded that the maximum likelihood estimator resulting from the 'case load weighting' of the stratum-specific attributable risk estimates will be the best overall choice in all practical situations with relatively large sample sizes. Other adjusted attributable risk estimators depend heavily on the underlying structure of the multinomial model. PMID- 1293671 TI - A bootstrap resampling procedure for model building: application to the Cox regression model. AB - A common problem in the statistical analysis of clinical studies is the selection of those variables in the framework of a regression model which might influence the outcome variable. Stepwise methods have been available for a long time, but as with many other possible strategies, there is a lot of criticism of their use. Investigations of the stability of a selected model are often called for, but usually are not carried out in a systematic way. Since analytical approaches are extremely difficult, data-dependent methods might be an useful alternative. Based on a bootstrap resampling procedure, Chen and George investigated the stability of a stepwise selection procedure in the framework of the Cox proportional hazard regression model. We extend their proposal and develop a bootstrap-model selection procedure, combining the bootstrap method with existing selection techniques such as stepwise methods. We illustrate the proposed strategy in the process of model building by using data from two cancer clinical trials featuring two different situations commonly arising in clinical research. In a brain tumour study the adjustment for covariates in an overall treatment comparison is of primary interest calling for the selection of even 'mild' effects. In a prostate cancer study we concentrate on the analysis of treatment-covariate interactions demanding that only 'strong' effects should be selected. Both variants of the strategy will be demonstrated analysing the clinical trials with a Cox model, but they can be applied in other types of regression with obvious and straightforward modifications. PMID- 1293672 TI - A latent class model for repeated measurements experiments. AB - Standard models for the analysis of repeated measurements assume a common response profile for all experimental units within a treatment group. However, in many applications this under-represents the nature of the response. There may be several distinct modes of response within a group (for example, responders versus non-responders to a given treatment), or there may be a set of distinct response profiles which are common to all the treatment groups. In these situations the effect of treatment can be characterized both by the shape of the fitted profiles and by estimating the proportion of cases who exhibit each particular response profile. This paper describes how such experiments may be analysed through the introduction of a latent variable into the standard model. Maximum likelihood estimation is straight-forward using the EM algorithm. Model choice requires some care, but good-fitting models can be identified via inspection of residuals and the use of empirical semi-variogram plots. Once the number of distinct profiles has been determined, treatment effects can be investigated using likelihood-ratio statistics. The approach is illustrated with a re-analysis of a dataset first described by Grizzle and Allen. PMID- 1293673 TI - Analysis of factors influencing the efficacy of pooled platelet transfusions. AB - The results of 839 platelet transfusions in 115 patients were studied to establish the relative importance of 10 clinical factors in determining the efficacy of pooled donor transfusions. Efficacy was measured by the one hour corrected increment in platelet count. The number of transfusions available for study from individual patients varied widely from 1 to 37. Two methods of analysis are presented. The first makes assumptions about the correlation between transfusions within patients, and the variation between patients. The second is based on a repeated sampling procedure whereby unbiased estimates of the parameters of interest are obtained from random samples containing only one transfusion per patient. PMID- 1293674 TI - Identification of pulses in hormone time series using outlier detection methods. AB - The identification of discrete hormonal secretory pulses is of critical importance in clinical endocrinology. Pulses are defined as sudden increases in hormone concentration followed by exponential decay. We propose a model-based iterative procedure for pulse detection in pulsatile hormone time series. Our model is seen to be analogous to the model for innovation outliers in autoregressive series, and outlier detection techniques for pulse identification are adapted to the endocrine context. An original feature of the procedure is that it distinguishes between true pulses and gross observation outliers in the series. Simulation experiments are used to investigate the behaviour of the method under physiologically or clinically relevant circumstances. Five experimental endocrine series from rhesus monkeys, where the times of the pulses are known from the concomitant recording of the electrical activity of the hypothalamus, are analysed. PMID- 1293676 TI - [Stressed out? Me? Never...!]. PMID- 1293675 TI - 24-hour blood pressure measurement in antihypertensive drug trials: data requirements and methods of analysis. AB - Non-invasive ambulatory blood pressure monitoring is an appropriate technique for the identification of the target population requiring antihypertensive treatment, since the systematic bias seen in casual clinic measurement is removed. The use of the technique in controlled clinical trials leads to a reduction in the sample size required to show a treatment difference in antihypertensive effect compared to sporadic single measurements, although in practice the number of recruited patients can considerably exceed the number of evaluable patients, due to poor compliance or incompleteness of data. In addition, the equality of observation essential in clinical trials cannot be controlled to the same degree as is possible with clinic measurements. Comparison of estimators of the overall characteristic blood pressure reveals that the 24-hour mean value produces an adequate estimator. A description of the individual blood pressure profile is obtained using smoothing procedures, the moving interval average providing a robust and simple approach. Clinically meaningful characteristics of the profile are difficult to define due to a dearth of information on prognostic importance of the features of the 24-hour blood pressure profile. Smoothed individual profiles can be combined to produce graphical descriptive treatment group summaries. PMID- 1293678 TI - [The grape cure]. PMID- 1293677 TI - [A vaccine has arrived for little children]. PMID- 1293679 TI - [Nurses, patients ... all go to the country!]. PMID- 1293680 TI - [France-Canada, evaluation of an exchange program]. PMID- 1293681 TI - [The plague still exists]. PMID- 1293682 TI - [Until death, terminal care ... at home]. PMID- 1293683 TI - [Private practice nurses: adhering to an approved association]. PMID- 1293684 TI - [Inside the ear]. PMID- 1293685 TI - [Public health system]. PMID- 1293686 TI - [Maastricht and public health]. PMID- 1293687 TI - [Overcoming visual handicap ... addresses to know]. PMID- 1293688 TI - [Solidarity in the hospital, it exists!]. PMID- 1293689 TI - [Social treatment of AIDS]. PMID- 1293690 TI - [A day with Catherine Dupont at Fenelon. Interview by Virginie Champion and Isabelle Lefevre]. PMID- 1293692 TI - [School lunches, reality-oriented menus]. PMID- 1293691 TI - [Anne Beurmier, school nurse at Noisy-le-Sec. Interview by Virginia Champion and Isabelle Lefevre]. PMID- 1293693 TI - [Freeze drying: at school too!]. PMID- 1293694 TI - [Cleaning and disinfection protocol for endoscopes]. PMID- 1293695 TI - [Bacteria and man]. PMID- 1293696 TI - [Nursing staff: legislation and responsibility. 1st Part: Malpractice responsibility]. PMID- 1293697 TI - [Nutrition from 7 to 14 years old]. PMID- 1293698 TI - [Bandages, their functions and quality]. PMID- 1293699 TI - [The first role of a mobile unit is pedagogic]. PMID- 1293700 TI - [Nursing role in a palliative care unit]. PMID- 1293701 TI - [Nursing staff: legislation and responsibility. 2nd part: The responsibility of hospital supervisors]. PMID- 1293702 TI - [At Vaugirard, a new approach to geriatrics]. PMID- 1293703 TI - [A liaison notebook for a new hospital: the communication tool between the Vaugirard Hospital and the XV district]. PMID- 1293704 TI - [The electrocardiogram]. PMID- 1293705 TI - [Justice and AIDS]. PMID- 1293706 TI - [A day with a movie industry nurse. Interview by Virginie Champion and Isabelle Lefevre]. PMID- 1293707 TI - [Professional status of movie industry nurses project]. PMID- 1293708 TI - [The "House of Diabetes", what is its purpose?]. PMID- 1293709 TI - [The education of the child with diabetes at home]. PMID- 1293710 TI - [Diabetes: rapid diagnostic tests]. PMID- 1293711 TI - [Antidiabetic drugs]. PMID- 1293712 TI - [The diabetic child and his parents]. PMID- 1293713 TI - [The non-insulin-dependent diabetic]. PMID- 1293714 TI - [Help for smoking cessation in industry]. PMID- 1293715 TI - [Information on AIDS in industry]. PMID- 1293716 TI - [Hepatitis B in the workplace]. PMID- 1293717 TI - [Tendon pathology of the hand and wrist and tunnel syndromes of professional origins]. PMID- 1293718 TI - [The evolution of the nursing profession]. PMID- 1293719 TI - [European training]. PMID- 1293721 TI - [Studies, training and diplomas]. PMID- 1293720 TI - [Professional identity]. PMID- 1293722 TI - [Training objectives for the training in nursing care at the diploma level]. PMID- 1293723 TI - Effect of natural naphthoquinones in BALB/c mice infected with Leishmania amazonensis and L. venezuelensis. AB - Plumbagin, 3,3'-biplumbagin and 8,8'-biplumbagin are naphthoquinones isolated by activity-directed fractionation from a Bolivian plant, Pera benensis, used in folk medicine as treatment of cutaneous leishmaniasis caused by Leishmania braziliensis. BALB/c mice were infected with L. mexicana or L. venezuelensis and treated 24 h after the parasitic infection with plumbagin (5 or 2.5 mg/kg/day), 3,3'-biplumbagin, 8,8'-biplumbagin (25 mg/kg/d) or Glucantime (200 mg/kg/d). Lesion development was the criteria employed to evaluate the inhibitory effect. The bis-naphthoquinones were less potent than Glucantime against L. amazonensis and L. venezuelensis. Plubagin and Glucantime delayed the development of L. amazonensis and L. venezuelensis. Assays of a single local treatment on foot-pad infection two weeks after the parasitic inoculation with L. amazonensis showed that 8,8'-biplumbagin (50 mg/kg/d) was as potent as Glucantime (400 mg/kg/d). PMID- 1293724 TI - An in vitro bioassay for quantification of melarsoprol in serum and cerebrospinal fluid. AB - A biological assay was developed for measuring melarsoprol in serum and cerebrospinal fluid of patients with human African trypanosomiasis. Trypanosomes were cultivated in microtiter plates for 72 hours with melarsoprol (Mel B) in concentrations of 1.25 micrograms/ml to 2.2 ng/ml. The minimum inhibitory concentration of Mel B for a reference Trypanosoma brucei rhodesiense clone was determined by microscopical examination. Samples of serum or cerebrospinal fluid were incubated under the same conditions and the highest dilution determined which caused death of all trypanosomes. The melarsoprol concentration of the sample was then calculated using the sample dilution and the determined minimal inhibitory concentration of the trypanosome population used for the assay. The test was validated using a number of reference samples and it was used for melarsoprol determination in serum- and cerebrospinal fluid samples taken from two treated patients. A sample size of 100 microliters was sufficient to perform the assay. The lower detection limit was 9 ng/ml (22.6 nmol/ml). The assay has potential for measuring other trypanocidal drugs in body fluids. PMID- 1293725 TI - Preliminary observations on the efficacy of mel Cy (Cymelarsan) in domestic animals infected with stocks of Trypanosoma brucei brucei and T.b. evansi. AB - The trypanocidal activity of an arsenical compound (RM 110; mel Cy; Cymelarsan) was evaluated against Trypanosoma brucei brucei and T. brucei evansi in cultures, in goats and pigs. The trypanosome stocks used differed in their levels of susceptibility to cymerlarsan in an in vitro test, their IC50 values (drug concentration which inhibits growth by 50%) ranging from 4.8-5.1 nM for susceptible, and 26.9 nM for a resistant stock. Goats infected with a susceptible T.b. evansi stock were cured after a single injection of 0.3 mg/kg cymelarsan. In three out of four goats chronically infected with the same stock a single injection of 0.625 mg/kg cymelarsan effected a cure, whereas the goat in which the infection relapsed was finally cured after injection of 0.625 mg/kg on each of three consecutive days. A single dose of 2.5 mg/kg did not cure goats infected with an arsenical-resistant T.b. brucei stock. One of two pigs chronically infected with arsenical-susceptible stocks of T.b. brucei was cured after a single injection of 0.625 mg/kg cymelarsan, whereas the other one relapsed and died. In conclusion, the results may indicate that the dose of 0.25 mg/kg recommended by the manufacturer is too low and that a single may not cure animals with CNS involvement with certainty. The recommended dose might therefore have been applied strictly for the treatment of camels only. PMID- 1293726 TI - Risk factors for deaths in children under 5 years old in Bagamoyo district, Tanzania. AB - We conducted a population based case control study of deaths in children < 5 years old from Bagamoyo District, Tanzania, to evaluate factors associated with death, and factors associated with not utilizing Government health care system. Six hundred and ten children who died between 1 July, 1986 and 30 June 1987 were enrolled as cases; 1,160 healthy control children were selected by multistage random cluster sampling. Twenty-five percent of deaths were ascribed to pneumonia based on "verbal autopsy"; 39% of acute respiratory deaths occurred in children < 6 months of age. In a multivariate analysis, significant independent associations were found with mother as sole decision maker for treatment (O.R = 0.13; 95% C:I. 0.07, 0.22); use of water from village well, pond, or river vs. tap water (O.R. = 11.86; 95% C.I., 5.46, 25.72); the child eating with others (O.R. = 9.42; 95% C.I. 5.68, 15.62) and the child sleeping in the room where cooking is done (O.R. = 2.78; 95% C.I. 1.79, 4.33). Overall only 45% of families utilized Government health care (village health worker, dispensary or health centre) during their child's terminal illness. Families utilizing Government health care were significantly more likely to say that the mother alone could make treatment decision (O.R. = 2.49, 95% C.I. 1.39, 4.46), and to be closer to a dispensary. The main reasons for not utilizing Government health care were 'traditional medicine is better' (41%) and 'no drugs available' (38%). PMID- 1293727 TI - Perception of risk for malaria and schistosomiasis in rural Malawi. AB - A sample of 120 individuals--representative of the Malawian population in terms of gender and age distribution--were interviewed regarding their perceptions of the diseases malaria and schistosomiasis. Particular attention was paid to judgements regarding the level, seriousness, predictability and controllability of these health risks. Sample sites were lowland marshland areas where both diseases were highly prevalent. Individuals were also asked about their adherence to recommended malaria and schistosomiasis control and prevention procedures. Respondents commonly rated malaria and schistosomiasis both unpredictable and uncontrollable. For malaria, no risk judgements predicted level of adherence to prevention guidelines. That is, individuals' perception of malaria risk bore no influence on whether or not they engaged in recommended behaviour. For schistosomiasis, seriousness of infection (at one sample site) and the predictability and controllability of infection (at the other sample site) predicted such adherence. Analysis of the influence of factors such as age, gender and level of education confirmed distinct patterning or responses for the two health risks. Whilst adherence to preventative guidelines for schistosomiasis is influenced by personal perceptions of risk, it appears that social factors may exert more influence on the extent of compliance with malaria control and prevention procedures. Distinct approaches to health education regarding malaria and schistosomiasis may, therefore, be warranted, with the former emphasising community responsibility and participation, and the latter individual actions which may reduce risk. PMID- 1293728 TI - Analysis of ecdysteroids in the trematodes, Schistosoma mansoni and Fasciola hepatica. AB - Adult Schistosoma mansoni from experimentally infected mice and Fasciola hepatica recovered from ovine livers post mortem were analyzed for free and conjugated ecdysteroids by radioimmunoassay, high-performance liquid chromatography monitoring fractions by radioimmunoassay, and by capillary gas chromatography/mass spectrometry (selected ion monitoring). Both species contained ecdysone and 20-hydroxyecdysone as free ecdysteroids and as polar conjugates. F. hepatica also contained a polar conjugate of 2-deoxyecdysone. Evidence of apolar ecdysteroid conjugates was only obtained for F. hepatica. The free ecdysteroid-containing fraction of S. mansoni contained small amounts of unidentified immunoreactive material. PMID- 1293729 TI - Ultrasound versus clinical examination as indication for Schistosoma mansoni associated morbidity in children. AB - In order to compare clinical versus ultrasound based diagnosis of Schistosoma mansoni induced periportal fibrosis (pF) 536 infected Sudanese schoolchildren underwent clinical and sonographical examination. A liver exceeding 3 cm in sternal line and a palpable spleen were considered pathological. Ultrasound criteria for age dependent organometry of a Central European cohort were used as reference. Based on clinical criteria 190 children (35.4%) had hepatomegaly, whereas according to ultrasound results the rate was only 11.4%. Splenomegaly was detected in 77 cases (14.4%) by clinical means, but in 196 by ultrasound (36.6%). The sensitivity of clinical parameters as indication of pF was around 50%. Results for ultrasound detected organomegaly were only slightly better. It was concluded that assessment of liver and spleen sizes was of limited value as an indication for pF and that a considerable discrepancy existed between clinical and ultrasound based assessment of hepato- and splenomegaly. PMID- 1293730 TI - Paragonimiasis in Ecuador: prevalence and geographical distribution of parasitisation of second intermediate hosts with Paragonimus mexicanus in Esmeraldas province. AB - To determine whether the human cases of pulmonary paragonimiasis detected in the province of Esmeraldas were autochthonous a total of 1,457 freshwater crabs, species Hypolobocera aequatorialis, were collected from 45 different streams in 4 cantons to determine the rate of parasitisation with metacercariae of Paragonimus mexicanus. Some 28 (62.2%) streams were found to harbour parasitised crabs, with 76.5% of the streams in canton Quininde infected, followed by those in Muisne, 72.7%, Esmeraldas, 62.5% and Eloy Alfaro 22.2%. Of the 1,043 crabs studied from these 28 streams, 42.6% (444) were found to be parasitised with metacercariae: 45.1% of the crabs in the streams in the canton of Quininde, 43.9% in Muisne, 37.4% in Esmeraldas and 13.2% in Eloy Alfaro. There was a positive correlation between the crab parasitisation and the increasing size of their carapace. The results indicate that there is potential active transmission of disease in the four cantons in the province of Esmeraldas and that the human cases detected are probably autochthonous. PMID- 1293731 TI - First record of Angiostrongylus cantonensis (Chen, 1935) (Nematoda: Metastrongylidae) in the Dominican Republic. AB - Rats, Rattus norvegicus, trapped in some sections (barrios) of the city of Santo Domingo, the capital of the Dominican Republic showed that 5 of them from two barrios harbored the nematode Angiostrongylus cantonensis in the pulmonary artery. Macerated and digested terrestrial snails, Subulina octona, collected from the backyards of houses where the rats were trapped contained L2 and L3 larvae of the nematode. The morphology of the adult worms and the larvae was consistent with that described for A. cantonensis in the literature. This is the first report of this Oriental and Western Pacific nematode in the Dominican Republic and the fourth in the Americas. Gastrointestinal hemorrhage, a rare symptom due to another species, the American A. costaricensis, which occurs in mesenteric arterioles of rodents and humans, is in the recent literature; the patient was a 41-year old Dominican. Thus the Dominican Republic is the first country in the Western Hemisphere to have the two species of Angiostrongylus. PMID- 1293732 TI - The effect of repeated doses of ivermectin on adult female Onchocerca volvulus in Sierra Leone. AB - The effects of single and multiple doses of ivermectin on mortality and morphology were assessed in over 700 female Onchocerca volvulus worms and the effects on embryogenesis were assessed in 490. Nodules were surgically removed from Sierra Leoneans recruited from a double-blind placebo controlled study of ivermectin given at six-monthly intervals. Nodules were digested in collagenase to isolate whole adult worms. After four or five doses of ivermectin there were significant increases in the numbers of discoloured and calcified worms and possibly a trend towards increased mortality, but this was not seen consistently. There was no evidence of a prophylactic effect of the drug. Worms were then homogenised and embryograms constructed. A single dose of ivermectin produced large numbers of degenerating intrauterine microfilariae, but embryonic development occurred normally. After multiple doses we observed almost complete cessation of embryogenesis, with a highly significant decrease in the numbers of viable multicellular embryonic stages, while oocytes appeared to be produced normally. Development is probably impeded at the single cell stage, possibly because of reduced fertilization. In planning the future role of ivermectin as a control measure for onchocerciasis it is crucial to determine if these effects on embryogenesis are reversible. PMID- 1293733 TI - Results of a safety trial on single-dose treatments with 400 mcg/kg of ivermectin in bancroftian filariasis. AB - Two groups of Polynesian Wuchereria bancrofti carriers, 17 females aged 21 to 84 years and 20 males aged 26 to 57 years, in whom microfilaraemia ranged from 1 to 10,121 mf/ml and from 1 to 6,484 mf/ml, respectively, were given a supervised singledose treatment with 400 mcg/kg of ivermectin. Carriers were examined and questioned regarding their experience of adverse reactions, which were graded 0 to 3 according to severity, at 6, 12 and 24 hours and at 4 days after treatment. Biological examinations which included determination of microfilaraemia, complete blood count, liver function tests and assessment of creatinine and urea levels were performed at 4 days before and 4 days after treatment. Adverse reactions were observed in 65% of female and in 70% of male carriers; they were of grade > or = 2 in 35% of carriers in both groups. None as considered serious; they all disappeared in 24-48 hours. The main symptoms were headache, fever > or = 37.5 degrees C and myalgia in females. One male vomited 3 hours after treatment; as a result the drug was not ingested and no decrease of microfilaraemia was noted. Twelve days afterwards, he was given a second 400 mcg/kg dose, he experienced again a grade 1 reaction and his microfilaraemia fell to zero. The 37 carriers in the present study were matched with 37 other Polynesian carriers treated with a 100 mcg/kg single dose of ivermectin in previous trials for pretreatment mf density and sex: no significant difference could be found in adverse reactions between the 2 treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293734 TI - The selection of communities for treatment of onchocerciasis with ivermectin. AB - In areas endemic for onchocerciasis, active community-based treatment with ivermectin is preferred to individual diagnosis and treatment. Ideally, all infected persons should be treated, although initially priorities may have to be set at local or national levels. We suggest that all communities with a prevalence of O. volvulus infection of 20% or more in adult males aged 20 years or over should be treated; and that elsewhere facilities for passive treatment should be provided. In some areas, for logistical reasons, treatment may first have to be started in communities with the highest prevalences (perhaps above 40% or even 60%) and then expanded to all endemic communities. The available data suggest that a rapid assessment method based on the examination for nodules will give a simple, acceptable, non-invasive and reasonably reliable method of identifying the communities that should be treated. If a nodule is detected in at least three men from a sample of 30 men aged 20 years or over, the community can be assumed to have a true prevalence of infection of 20% or more and should be included in community-based treatment. PMID- 1293735 TI - Expression of an active cathepsin B-like protein Sm31 from Schistosoma mansoni in insect cells. AB - Recombinant Schistosoma mansoni cathepsin B was produced in insect cells via the baculovirus expression vector system as a 37.5 kDa precursor molecule and a 31 kDa mature enzyme. Extracts prepared from cells infected with the recombinant virus were able to cleave a synthetic dipeptide substrate specific for cathepsin B. Proteolytic activity was inhibited by trans-epoxysuccinyl-L-leucyl-amido (4 guanidino) butane (E64) but not by phenylmethylsulphonyl-fluoride (PMSF), pepstatin and 1,10-phenanthroline. Specific inhibition by diazomethylketone derivatives, which bind covalently to the active centre of cysteinyl proteinases was also demonstrated. PMID- 1293736 TI - Serum TNF in patients with severe malaria treated by exchange transfusion. AB - The authors report on three cases of severe P. falciparum malaria successfully treated by iv quinine and exchange transfusion. Serum concentrations of Tumor Necrosis Factor (TNF) were determined before and during treatment. After an initial decrease, serum levels of TNF remained markedly elevated during the first 48 hours despite exchange transfusion. Though exchange transfusion accelerates the elimination of parasites from the blood, it seems to have no immediate effects on reducing serum levels of cytokines such as TNF. PMID- 1293737 TI - Genetic causes of stillbirth. PMID- 1293738 TI - Frequency and load of congenital anomalies in a neonatal intensive care unit, prenatal diagnosis, and perinatal management. PMID- 1293739 TI - Vascular changes in the eye of the newborn infant. PMID- 1293740 TI - The newborn with ambiguous genitalia. AB - The unexpectedness of genital ambiguity in an infant creates an urgent and stressful situation. A logical approach, using a team of specialists together with nursery staff and physicians, allows each member to contribute expertise and unnecessary overlap of investigations. The psychological needs of the parents should be recognized, because their relation with the infant will determine the success of the assigned gender role in the future. PMID- 1293741 TI - Ethical issues presented by children with congenital anomalies. PMID- 1293742 TI - Role of nontraditional inheritance in congenital anomalies. PMID- 1293743 TI - Human congenital anomalies: application of new genetic tools and concepts. AB - The discovery of nontraditional inheritance and of developmental gene families common to all metazoans has revolutionized research on human congenital anomalies. The most gratifying results of these new concepts are summarized in Table 5: several human syndromes have already been related to their causative genes. Classic embryonic mechanisms (ie, gastrulation, segmentation, adhesion) also have been correlated with specific molecules. Perhaps most optimistic are the facts that many of the relevant molecules can be viewed as growth factors and that many anomalies are examples of extended or arrested development known as heterochrony. The implication is that genetic screening and preconceptional diagnosis will allow treatment of congenital malformations by supplementation/suppression of the maternofetal unit. This future specialty of "gestational endocrinology" is already being used for embryonic therapy of 21 hydroxylase deficiency. PMID- 1293744 TI - [Effect of norepinephrine on the frontal neuron activity related to delayed discrimination task in monkeys]. AB - To study the role of norepinephrine (NE) in the cognitive function of the brain, the effects of NE, tolazoline (TOL) and propranolol (PR) on the activity of frontal neurons were examined in 3 rhesus monkeys (Macaca mulatta) during the performance of a delayed visual discrimination go/no-go task. Of the 230 task related neurons recorded from the area medial to the superior ramus of the arcuate sulcus, 159 neurons were tested with NE applied microiontophoretically. Of these tested neurons, 11 neurons were related to starting period, 28 neurons to cue period, 66 neurons to delay period and 54 neurons to response period. About 2/3 of these neurons increased in discharge rate in the task, and the rest decreased. For most of the neurons with decrease of discharge rate in the delay period, the discharge rate was further decreased during application of NE. During application of TOL or PR, the discharge rate was increased and the effect of NE was antagonized. The present results suggest that NE may play a role in the cognitive function of the frontal neurons, particularly in attention and short term memory, and may be involved in the inhibitory process of the neuronal activities. PMID- 1293745 TI - [Antagonistic effect of electro-acupuncture analgesia with Ca2+ injection into habenula could be reversed by gallamine triethiodide]. AB - .1 mol/L CaCl2 0.5 microliters, 0.06 mol/L ACh 0.5 microliters, 5.4 x 10(-3) mol/L gallamine triethiodide (cholinergic nicotinic receptor blocker) 0.5 microliter and 14.4 x 10(-3) mol/L atropine (cholinergic muscarinic receptor blocker) 0.5 microliter were injected through bilateral intracranial cannulae in rat habenula. Pain threshold was measured by the latency of tail-flick reflex elicited by radiant heat exposure before and after intracerebral injection. CaCl2 significantly reduced the basic pain threshold and weakened the effect of the acupuncture analgesia. ACh apparently antagonized the effect of acupuncture analgesia. Gallamine triethiodide could recover the pain threshold almost to the raised level by acupuncture, but atropine only strengthened the effect on pain threshold weakly and briefly. The results suggest that the antagonistic effect of Ca2+ may be mediated via ACh in habenula. PMID- 1293746 TI - [Simple spike response of cerebellar Purkinje cells to stimulation of C-fiber in saphenous nerve]. AB - Simple spike of cerebellar Purkinje cells (PC-SS) was recorded with microelectrode. In the NCCVF (normalized cross-covariance function) histogram, spontaneous PC-SS does not show obvious peak. When the saphenous nerve is stimulated at lower intensities, which elicits the A-fiber input only, the discharge response (A-CED) consists of an early component with a latency of 16.7 +/- 0.9 ms and a late component with a latency of 270.8 +/- 12.8 ms. After A fibers are blocked selectively by polarizing current, the stimulation at a suprathreshold strength for C-fiber evokes a characteristic response (C-CED) with a latency of 142.4 +/- 4.3 ms. However, the C-CED can not be evoked by the inputs of A- and C-fiber simultaneously. In NPSDF histogram, the spontaneous activities of PC-SS can be divided into two groups, the high and the low peak group. The high peak group (n = 15) has a peak energy value of 15.7 +/- 4.7 x 10(-3) and peak frequency of 4.07 +/- 1.69 Hz. A-fiber input causes an increase of the peak value, while C-fiber input causes a decrease. The low peak group (n = 16) has a peak energy value 8.4 +/- 1.4 x 10(-3) and peak frequency of 3.67 +/- 2.90 Hz. Both A-fiber and C-fiber inputs cause an increase of the peak value, but the effect of A-fiber input was more prominent. The results show that the pure C fiber input can reach the cerebellar PC and elicit characteristic simple spike response. PMID- 1293747 TI - [Relationship between neuronal activities of the guinea-pig inferior mesenteric ganglion neurons and muscular contraction of the colon in vitro]. AB - A perfused inferior mesenteric ganglion (IMG)-colon preparation was prepared from the guinea-pig for intracellular recording of IMG neurons and for simultaneously recording the muscular contraction. It was found that: (1) At zero preloaded tension of colon, the spontaneous fast excitatory post-synaptic potentials (f EPSPs) could be recorded in about 50% sampled neurons. These f-EPSPs were abolished by either severing the colonic nerve or superfusing IMG with d tubocurarine (d-TC, 50 mumol/L). (2) The contraction of circular but not longitudinal muscle was augmented and slowed down by superfusing IMG with d-TC or low Ca/high Mg solution. (3) A train stimulation of the preganglionic nerves initiated a volley of f-EPSPs or orthodromic discharges, in the IMG neurons and a quick relaxation of the longitudinal muscle with a latency of between 0.1 s and 0.2 s. The responses of the neuron and the muscle could be eliminated by superfusing IMG with d-TC. Multiple irregular responses of the circular muscle of the colon to the train stimulation could also be found. The results suggest that the IMG neurons participate in the cholinergic afferents and colo-colonic reflex mediated by cholinoceptors. The output of the reflex mainly inhibited the circular muscle contraction of the colon. PMID- 1293748 TI - [Changes of central glucose metabolism following caudate stimulation produced analgesia in the rat--an autoradiographic deoxyglucose A study]. AB - Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia. PMID- 1293749 TI - [Inhibition of dopamine on WDR neurons of dorsal horn not antagonized by phentolamine and naloxone in rats]. AB - The inhibitory effects of dopamine (DA) applied spinally on the wide dynamic range (WDR) neurons of dorsal horn in rats were studied with extracellular recording technique. 54 WDR units were tested from 43 rats. With a dosage of DA from 0.26 x 10(-6) to 1.58 x 10(-6) mol/kg, the inhibitory effect of the neurotransmitter on the responses of dorsal horn neurons to noxious transcutaneous electrical stimulation exhibited a gradual increase. After DA (0.52 x 10(-6) mol/kg) administration, the inhibitory effect of DA began to appear in 5 min and reach to maximum in 15 min, whereupon the maximum level could be maintained for about 25 min. This effect of DA could be reversed completely by dopaminergic receptor antagonist, droperidol (0.66 x 10(-6) mol/kg) but not by 2.65 x 10(-6) mol/kg phentolamine or 1.37 x 10(-6) mol/kg naloxone. The results of the present investigation suggest that DA may be involved in the modulation of nociception at the spinal level as an independent neurotransmitter. PMID- 1293750 TI - [Guiding effect of embryonic fimbria graft on cholinergic fiber growth in hippocampus of adult rats]. AB - In view of the fact that in embryonic and neonatal central nervous system (CNS), the pathway of developing fiber tracts is capable of guiding the axonal growth, it would be interesting to know whether a similar effect exists on the axonal growth in adult CNS. Embryonic fimbria was grafted into the hippocampus of the adult rat. Two weeks later, the grafts were examined for cholinergic fibers with AChE histochemical method. It was found that a lot of cholinergic fibers appeared in the embryonic graft, but none of them in the adult fimbria graft as control. If the fimbria-fornix was transected at the time of grafting, no cholinergic fibers could subsequently be detected in both the embryonic graft and the host hippocampus. If a suspension of embryonic fimbria was used as a graft, only a few of long cholinergic fibers could be found in the grafted area. However, if tissue fragments of embryonic fimbria adhered to a strip of nitrocellulose filter were grafted as previously, numerous cholinergic fibers from the host hippocampus were found to be attracted around the strip and grow along the surface of the filter. The results seem to indicate that grafted embryonic fimbria or its tissue fragments are able to guide cholinergic fiber growth in adult hippocampus. It is possible that embryonic fimbria and other pathways of developing CNS fiber tracts provide a natural substrate for guiding axonal growth in adult CNS. PMID- 1293751 TI - [Alteration of calcium uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum in rat during ischemia-reperfusion]. AB - Using Langendorff's perfusion model of isolated rat heart, the effect of period of ischemia, ischemia-reperfusion and changes in perfusate pH on the function of calcium uptake of cardiac sarcoplasmic reticulum (SR) was observed. The initial rate and capacity of calcium uptake by SR decreased significantly after 25 min ischemia, and were further worsened when ischemia was prolonged to 40 min. When hearts were subjected to 15 min reperfusion after 25 min ischemia, calcium uptake capacity and initial rate decreased even more in comparison with that of 40 min ischemia. In addition, the calcium dependent ATPase activity of SR was also markedly inhibited. Reperfusion with acid (pH 6.8) or alkaline (pH 8.0) made no significant difference on the aforementioned reperfusion induced changes. The results indicated that myocardial ischemia depressed the calcium transport activity of SR, and this depression was further aggravated with prolonging ischemia. Reperfusion after ischemia exacerbated the ischemic injury. Reperfusion with either acid or alkaline Krebs-Henseleit solution could not improve the calcium uptake function of SR, implying that the pH change does not seem to be an important factor in inducing the SR dysfunction during ischemia-reperfusion. PMID- 1293752 TI - [Role of sulfhydryl compounds in the oxygen radical induced injury of isolated gastric mucosal cells]. AB - Gastric mucosal cells were separated by pronase-EDTA method and cultured. The cellular injury was produced by oxygen radicals provided by xanthine oxidase(XO) xanthine(X) system. When the cells were subjected to the action of XO-X system, the cellular viability was decreased and leakage of lactate dehydrogenase (LDH) from the cells was significantly increased. In addition, the cellular contents of nonprotein sulfhydryls (NPSH) and protein sulfhydryls (PSH) were decreased. When the intracellular sulfhydryl content was decreased by N-ethylmaleimide (NEM, a depletor of endogenous sulfhydryls), the cell mortality and LDH leakage were increased in a time-dependent and dose-dependent manner. If glutathione or cysteamine (compounds containing-SH) was administered into the media, the cellular injury induced by XO-X system was notably inhibited, also in a dose dependent manner. The above results suggest that sulfhydryls may play an important role in the cell defending mechanism against injury of gastric mucosal cells by oxygen radicals. PMID- 1293753 TI - [Induction of Fos-like protein in the rat spinal cord following electroacupuncture stimulation]. AB - The expression of the c-fos proto-oncogene has been regarded as a marker for noxious stimulation. We now report that electroacupuncture (EA) stimulation (100 Hz, 0.3 ms, 1-2-3 mA, 30 min) delivered into the acupoint Sanyinjiao (SP6) could also induce the c-fos expression in the rat spinal cord as demonstrated by immunohistochemical technique using antibody against the c-fos protein product Fos. In rats receiving EA stimulation, numerous cells with Fos-like immunoreactivity (FLI) were observed in both dorsal and ventral horn of the spinal cord with dense labelling in laminae III and IV of the ipsilateral side. Only scattered FLI cells were found in laminae I and II. In contrast, FLI evoked by noxious stimulation (5% formalin injected at the hindfoot subcutaneously) was shown mainly in laminae I and II, rather than in III and IV. The c-fos expression was very low in control animals receiving neither formalin nor EA administration. The present study indicates that the site specificity of the c-fos expression induced by EA is different from that evoked by noxious stimulation. The possibility that EA-induced Fos protein might participate in acupuncture analgesia is currently under investigation. PMID- 1293754 TI - [Cardiovascular effects of microinjection of neuropeptide Y into lateral septal nucleus]. AB - Cardiovascular effects of microinjection of neuropeptide Y (NPY) into the lateral septal nucleus (LS) were investigated in anaesthetized rats. The microinjection gave rise to a significant increase in blood pressure and heart rate. The pressure response was dose-dependent but the tachycardia was not. Control injection of 0.9% saline into LS produced no haemodynamic response. PMID- 1293756 TI - [Preliminary study on the effect of endothelin on the contraction of isolated rat pulmonary artery and its mechanism]. AB - Experiment was performed on the rings of right pulmonary artery (PA) taken from male Wistar rats. Each ring was suspended in an organ bath (37 degrees C) containing Krebs solution, gassed with 95% O2-5% CO2 (pH7.40). The changes of vascular tension were measured. The contraction of PA to endothelin (ET) (10(-9) mol/L) and the effects of 764-3 (50, 100, 200, 300 micrograms/ml as a scavenger of superoxide anion), verapamil (3 x 10(-6) mol/L) NDGA, indomethacin, atropine, phentolamine, propranolol, ketanserin tartrate and diethylcarbamazine on the ET induced contraction were investigated. The results indicated that ET can induce a potent and sustained contraction of PA, inhibited by verapamil and 764-3, but unaffected by inhibitors of cyclooxygenase, lipoxygenase, leukotrienes systhetase or adrenergic, serotonergic, cholinergic receptors. It is suggested that the influx of extracellular Ca2+ and the production of superoxide anion might be involved in the ET-induced contraction. Arachidonate metabolism and receptors mentioned above probably didn't participate in the responses. PMID- 1293755 TI - [Stimulation of the brain osmoreceptor attenuates the sensitivity of tubuloglomerular feedback in rats]. AB - By using micropuncture technique and measuring inulin concentrations in plasma and tubular fluid, and tubular flow rate, single nephron glomerular filtration rate (SNGFR) was calculated. The effect of stimulation of the brain osmoreceptors on the sensitivity of tubulo-glomerular feedback in rats was observed. The SNGFR value measured at the proximal tubular (SNGFRp) was greater than that measured at the distal tubule (SNGFRd) of the same nephron. The difference between these two values (SNGFRp-d) was a measure of the extent of tubuloglomerular feedback (TGF). The SNGFRp-d value was reduced after intracerebroventricular administration of hypertonic saline (icv. HS), indicating that stimulation of the brain osmoreceptor can attenuate the sensitivity of TGF. The icv. HS-induced increase in renal plasma flow rate and glomerular filtration rate could be abolished by intravenous injection of furosemide, while natriuretic response persisted. These results suggest that icv. HS can alter renal hemodynamics via reduction of TGF, and confirm the claim that icv. HS can inhibit tubular reabsorption, which is responsible for the natriuretic response. PMID- 1293757 TI - [Use of a computer-controlled servo system to produce "ephysiological" contraction of isolated rat papillary muscle]. AB - A computer-controlled servo system consisting of an ergometer with a force displacement dual mode transducer, a Z-80 single-board microcomputer and a designed software was constructed. This servo system can be used to generate physiological contraction in isolated rat papillary muscle, in which the muscle went through a complete 4-phase cycle of force and length changes, similar to those undergone by muscle fibers in the beating heart during the cardiac cycle. This system is being used to investigate the tension-length relation and the network of isolated myocardium as well as the end-systolic tension-length relation and the force-velocity relation simultaneously. PMID- 1293758 TI - [Neurotensin excited neurons of the dorsal motor vagal nucleus: an in vitro study]. AB - Intracellular recordings were made from neurons of the dorsal motor nucleus of the vagus (DMV) in rat brain slices. Most of DMV neurons (88%) were depolarized by droplets or perfusion of neurotensin (NT) in a dose-dependent manner. The depolarization, accompanied by an increase in membrane resistance, depended on extracellular K+ concentration and reversed polarity at about -82 mV. Perfusion with Ca(2+)-free/high-Mg2+ solution or with 1 mumol/L TTX solution, which blocked synaptic activities, did not eliminate NT-induced depolarization. The results indicate that NT excites DMV neurons through postsynaptic mechanism and this exciting depolarization may result from a decrease in K+ conductance. PMID- 1293759 TI - [Involvement of vasopressinergic neurons of paraventricular nucleus in the electroacupuncture-induced inhibition of experimental visceral pain in rats]. AB - It has been demonstrated in animal model of somatic pain that hypothalamic paraventricular nucleus (PVN) participates in acupuncture analgesia, probably by mediation of vasopressin release. The role of PVN in acupuncture analgesia for experimental visceral pain in rats was further investigated in the present study. Experimental results demonstrated that electroacupuncture could inhibit the writhing response, produced by intraperitoneal injection of antimonium potassium tartrate and this inhibitory effect could be enhanced by electrical stimulation of PVN, but decreased by electrolytical lesion of PVN, intracerebroventricular injection of vasopressin antiserum (14 microliters) or the vasopressin antagonist, d(CH2)5Tyr(Me)-AVP (500 ng/5 microliters). Intraperitoneal administration of the latter drug (10 micrograms/kg), however, was ineffective. The above experimental results suggest that vasopressinergic neurons in PVN also participate in the inhibition of visceral pain by electroacupuncture. PMID- 1293760 TI - [Effects of intrahippocampal injection of 6-OHDA on acquisition and retention of avoidance response in rats]. AB - The role of hippocampal noradrenergic and dopaminergic transmission in the acquisition and retention of active conditioned avoidance behavior was investigated in rats by injection of 6-hydroxydopamine (6-OHDA) into dorsal hippocampus. The main results are as follows: (1) After injection of 6-OHDA the contents of dopamine, particularly norepinephrine (P < 0.01) in the hippocampus was decreased significantly. (2) The acquisition of conditioned avoidance behavior was markedly impaired. (3) The facilitating effect of AVP on retention of active conditioned avoidance behavior could be eliminated by prior injection of 6-OHDA bilaterally into hippocampus. PMID- 1293761 TI - [Effect of injection of enkephalin and bestatin in caudate-putamen on operant conditioning in rats]. AB - Female Wistar rats were trained in a Skinner-box, 30 trials per day in a dark room to establish operant defence conditioning. Training started with a light (15 s), then combined with footshock for further 8 s. When the rats learned to press the key to avoid footshock within 15 s, conditioned response was considered established. After the rats reached a conditioning rate (CR) above 80% for 5 days, cannulae were implanted into caudate-putamen. Two to three days later, Met enkephalin (MEK) or bestatin (an aminopeptidase inhibitor) was injected bilaterally into caudate-putamen. 30 min, 2 h, 24 h and 48 h after injection, conditioning tests were conducted, with each session consisting of 30 trials. Control experiments were done when 0.9% NaCl (NS) was injected. After injection of NS, CR maintained above 80% in all 4 test sessions. MEK (60 ng/rat) or bestatin (10 micrograms/rat) significantly lowered the CR during the 30 min and 2 h test session. In the latter case, the latency (L) was also prolonged. However both CR and L returned to the control level in the 24 h and 48 h test sessions. Naloxone (2 mg/kg, i.p.) blocked the conditioning-depression effect of bestatin. No significant alteration was seen in locomotor activity after MEK or bestatin injection. The results suggest that enkephalin in caudate-putamen may be involved in the regulation of retrieval of conditioning. Bestatin mimics the effect of MEK on conditioning reflex probably by increasing production of endogenous enkephalin. PMID- 1293762 TI - [Effects of stimulation and cauterization of hypothalamic paraventricular nucleus on acupuncture analgesia]. AB - The role of hypothalamic paraventricular nucleus (PVH) in acupuncture analgesia was investigated by local brain stimulation and cauterization. The results showed that electrical or L-glutamate sodium stimulation of PVH could enhance the effect of analgesia of Zusanli acupuncture, both in a dose dependent manner. Electrical cauterization of PVH decreased the effect of acupuncture analgesia, while removal of pituitary had no effect on the enhancing effect by L-glutamate sodium injection. PMID- 1293763 TI - [A voltage-dependent potassium channel of outward rectifier type in plasma membrane of oocyte from toad, Bufo bufo gargarizans]. AB - Membrane properties of the fully-grown oocytes from toad, Bufo bufo gargarizans, were studied by using voltage-clamp technique. It was found that a sustained outward current was elicited by membrane depolarization to -30 mV or more positive value. The increase of the current was nearly proportional to the degree of depolarization. The peak value of the current ranged 2-5 microA at a membrane potential of 20 mV in oocytes from different toads. The current was inhibited by antagonists of potassium channel, TEA and 4-AP. The concentration of TEA capable of inhibiting half of the current was 2.6 mmol/L. Chloride channel antagonist 9 AC (2.5 mmol/L) had no effect on the current. Triple the extracellular calcium concentration did not show any effect either. The reversal potential of the current varied with an increase of 47.3 mV per decade change of the extracellular potassium concentration. Changing extracellular concentration of sodium or chloride did not shift the reversal potential. It was concluded that the outward current was a voltage-activated potassium current. The voltage-dependent potassium current decreased after treatment of the oocytes with progesterone to a state of maturation. A large decrease of the current (to about 1/20 of the control) occurred to the oocytes obtained from hibernating toads while a less striking decrease of the current (to about 1/3 of the control) was observed in the oocytes from toads all year round reared at 25-30 degrees C. PMID- 1293764 TI - [Different changes in renal sympathetic nerve activity and adrenal sympathetic nerve activity produced by hemorrhage]. AB - The present study was undertaken to investigate the changes in renal sympathetic nerve activity (RSNA) and adrenal sympathetic nerve activity (AdSNA) due to acute hemorrhage in anesthetized rabbits. The animals were bled to a mean arterial pressure (MAP) of 5.3 kPa within 10 minutes from the femoral artery. Acute hemorrhage elicited a biphasic responses of RSNA with an initial excitation and a late inhibition during hemorrhage. But hemorrhage only induced a lasting excitation in AdSNA which could be abolished by sino-aortic denervation (SAD). Bilateral vagotomy either before or after hemorrhage could reverse the late inhibition in RSNA, but did not abolish the excitation in AdSNA. Intravenous injection of naloxone or microinjection of naloxone into rostral ventrolateral medulla (RVLM) could reverse the late inhibition in RSNA, but had no significant effect on the initial excitation in RSNA and AdSNA during hemorrhage. Hemorrhage induced heart (HR) change was similar that in RSNA, but could not be reversed by naloxone. These results indicate that the late inhibition in RSNA is mediated by inputs from vagus nerves and opiate peptide, particularly that in RVLM, and the excitation in AdSNA during hemorrhage is related to arterial baroreceptor reflex. PMID- 1293765 TI - [Inhibitory effect of transferrin on the binding and maintenance of FSH receptors in rat granulosa cells]. AB - It has been recently demonstrated that transferrin (TRF) can inhibit the functional differentiation of rat granulosa cells, but the mechanism remains unknown. In present experiment, the effect of TRF on the binding of 125I-rFSH to receptors and on the maintenance of FSH receptors in granulosa cells from immature, diethylstilbestrol treated rats were studied. The results show that the physiological range of TRF partially blocked the binding of 125I-rFSH to granulosa cells in a dose-dependent manner. TRF also dose-dependently inhibited the maintenance of FSH receptors in accordance with the reduced production of progesterone and estradiol. In view of the present and our previous investigation, it could be concluded that mechanisms of the inhibitory effect of TRF on the functional differentiation of granulosa cells mainly involve blockade of FSH binding to its receptors and inhibition of FSH receptor maintenance by FSH. PMID- 1293766 TI - [Plasminogen activators and plasminogen activator inhibitor type-1 in human endometrium]. AB - Two types of plasminogen activator (PAs) are present in human endometrium, and their contents vary with the different phases of menstrual cycle, i.e. high in the proliferative phase and low in the secretory phase. In the present study by immunohistochemical technique, both uPA and tPA antigens were demonstrated in the stromal and glandular cells of the endometrium. In cell culture, tPA was released only from stromal cells and uPA only from glandular cells as determined by SDS PAGE followed by fibrin overlay technique, but PA inhibitor type-1 (PAI-1) was secreted by both stromal and glandular cells. Furthermore, secretion of PAs from endometrial cells was enhanced by adding estradiol and markedly inhibited by progesterone in a dose dependent manner, while the PAI reacted just in the opposite way. The effect of the peptide hormones, hCG, GnRH, PRL, as well as cAMP in cell culture on the secretion of PAs and PAI was similar to that of estradiol, while forskolin demonstrated definitely more stimulative effect on tPA than uPA. Taking into account of the finding of the present study, it appears that, under hormonal control, a balance between PAs and PAI in the endometrium exists. The physiological roles of the PAs and PAI in the endometrium were discussed. PMID- 1293767 TI - [Cardiovascular responses to microinjection of atrial natriuretic peptide into ventrolateral medulla of rat]. AB - Application of atrial natriuretic peptides (alpha-ANP and AP III) to glutamate sensitive area of ventrolateral medulla produced a dose-dependent decrease in MAP and HR in anesthetized rats. Lower dosage of AP III induced hypotension without bradycardia, whereas the higher dosage of AP III decreased both blood pressure and heart rate. The results suggested that ANP may inhibit the medullary sympathetic center. PMID- 1293768 TI - [Effect of anoxia on the growth of cultured neurons from embryonic chick forebrain]. AB - Pure neurons from embryonic day 8 chick forebrain were cultured under anoxic condition (95% N2 and 5% CO2). After 24, 48 and 72 h in culture, MTT colorimetric microassay showed a reduced production of formazan, indicating that the neurons were seriously damaged. In addition, the glucose of the cultured media was significantly depleted. Even when glucose concentration was increased to 800 1,200 mg/100 ml, anoxia still caused neurons to die. The results indicate that brain neurons in embryo are sensitive to anoxia, and any protective influence of glia on anoxic neurons could not be mediated by supplying the latter with glycogen. PMID- 1293769 TI - [Study on zinc resistance to the immunosuppression caused by cyclophosphamidum in the mouse]. AB - Swiss mice were used to study the effect of zinc in antagonizing the suppressive action of Cy on the immune function and thymus structure. Mice (weighing 18-22 g) receiving daily dose of 0.2 mg zinc for 25 days did not show any change in peripheral WBC count, production of IgM antibody and thymus weight, but did display marked resistance to the reduction of WBC count and number of mature T lymphocyte, suppressed production of IgM antibody and decreased thymus weight due to administration of Cy. PMID- 1293770 TI - [Large-cell lymphomas: the International Prognostic Index]. PMID- 1293771 TI - [Non-Hodgkin's lymphomas. I. Clinico-biological features of 307 cases]. AB - PURPOSE: To assess the clinico-biological features appearing in 307 patients with non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: The clinical records of 338 patients diagnosed of NHL between January 1975 and December 1988 were revised in retrospect. All cases with histologic diagnosis of NHL aged over 14 years were included, and classified in accordance with the Working Formulation criteria. The following data were analysed: age, sex, first complaints, time elapsed since onset, histologic type, number of sites involved, bulky disease, anaemia, thrombocytopenia, LDH, stage, type of treatment and initial response, survival, and cause of death. The statistical evaluation was performed by actuarial analysis (Kaplan and Meier) and comparison (log-rank test) of survival. RESULTS: According to the three categories of the malignancies, the NHL were distributed into low-grade (37.8%), intermediate (36.1%) and high-grade (26.9%). The mean age of the series was 56.6 years and the M/F ratio was 1.3. Lymph node enlargement was the commonest finding; 36.4% of the patients had symptoms related with the disease, and 26.7% had bulky disease. Anaemia was present in 37.7% of the cases and thrombocytopenia in 14.3%, with similar distribution among the three grades. High LDH levels were found in 44% of the patients. At diagnosis, 85% of the patients were in advanced stages (III+IV) already. Complete response was attained in 51.1% of the cases, with median survival of 48 months. CONCLUSIONS: The clinico-evolutive data found here are similar to other reports in the literature. In one-half of the patients the cause of the first visit is lymph node enlargement. Complete remission is achieved by one out of two patients, this figure being similar for each of the histologic groups. The Working Formulation is useful in determining the different prognostic groups with respect to survival. PMID- 1293772 TI - [Non-Hodgkin's lymphomas. II. Analysis of the prognostic factors in a series of 307 patients]. AB - PURPOSE: To analyse different clinico-biologic data in order to assess their prognostic value in non-Hodgkin's lymphoma (NHL) patients. MATERIAL AND METHODS: The series comprises 307 patients with NHL diagnosed and treated between 1975 and 1988. The histopathologic diagnosis was revised in accordance with the working formulation system, three prognostic groups being thus considered: low-grade (LGL), intermediate-grade (IGL) and high-grade (HGL) lymphomas. Age, sex, clinical course prior to diagnosis, presence of B symptoms, histologic type, number of lymph-node areas involved, bulky disease, anaemia, thrombocytopenia, LDH, stage and response to therapy were all evaluated for the study. Survival curves were drawn with the Kaplan-Meier method, and the log-rank test was used for comparison of median survival. Whenever the univariate analysis achieved statistical significance, a multivariate analysis was performed by means of a multiple correlation and regression study in accordance with the Cox's model, in which the variables were expressed in a binary model. RESULTS: The following 8 values were found significant in the univariate study of low-grade lymphomas: age, number of involved areas, bulky disease anaemia, thrombocytopenia, LDH, stage, and initial response to treatment. In intermediate-grade lymphomas, the significant findings were age, number of affected areas, bulky disease, thrombocytopenia, LDH, stage, and initial response. For high-grade lymphomas, number of affected areas, thrombocytopenia, LDH, stage and initial response were found statistically significant. Although no significant differences were found for survival within each of the three grades, such differences were significant between them. In the multivariate analysis, age was significant only in the LGL (p < 0.0001) in IGL, age (p < 0.07) and initial response to therapy (p < 0.0001) achieved significant value, and in HGL, stage (p < 0.02) and initial response to treatment (p < 0.0001) attained significance. CONCLUSIONS: The univariate analysis provides various prognostic factors of statistically significance, as reported in the literature, but these after the multivariate analysis was applied, were reduced to age, stage and initial response to treatment. PMID- 1293773 TI - [Features of chronic myeloid leukemia at diagnosis. Study of a series of 134 cases]. AB - PURPOSE: To analyse the clinico-biological features of 134 patients with chronic myelogenous leukaemia (CML) at presentation. MATERIAL AND METHODS: The series is comprised of 134 patients from the Asturias Central Hospital and other hospital of the region, diagnosed of CML with conventional criteria between 1970 and 1989. A retrospective study was carried out revising the clinical records and the clinico-biological data at diagnosis. Cytogenetic studies were available in 62 cases. The statistical analysis was based upon descriptive statistics and comparison of means and proportions by the chi square and Student's tests. Univariate study was also performed for several variables. RESULTS: The mean age of the group was 50 years, ranging between 2 and 81. The M/F ratio was 76/58. The commonest symptoms at onset were those secondary to hypermetabolism and splenomegaly, 8% of the patients being asymptomatic. Splenomegaly was present in 73.8% of the patients and hepatomegaly in 37.6%. The median white cell count was 132 x 10(9)/L. Absolute basophilia and eosinophilia were seen in 83% and 78% of the cases, respectively. Anaemia was found in 47.4% of the patients, usually mild, and 39% of them had nucleated red cells in peripheral blood. The median platelet count was 400 x 10(9)/L. Thrombocytosis was found in 48% of the cases, while 11% had thrombocytopenia. The mean number of blast cells in the bone marrow was 1.72%. The histopathologic study of the bone marrow revealed decreased red cells in 94.5% of the patients and decreased megakaryocytes in 29.5%; these last were increased in 50% of the patients. Increased reticulin fibres were found in 38.5% of the bone marrow samples. In addition to the Ph' chromosome, which was present in 51 patients, chromosomal abnormalities were seen in 15.6% of the cases in the chronic phase and in 69.2% in the terminal stages of the disease. Positive correlation could be established between the white cell count and the size of spleen (p < 0.001) and liver (p < 0.05), and there was a negative correlation between white blood cell count and haemoglobin rate and platelet count (p < 0.05 for both). CONCLUSIONS: (1) The analysis of this series shows that the CML cases in this region have similar characteristics to those in other western world communities (2). The mean age of this group is somewhat higher than in other series, which should be re-evaluated after discarding the Ph'-negative cases. (3) There seems to be positive correlation between leucocyte count and spleen and liver enlargement, and negative correlation between leucocyte count and haemoglobin and platelet count. PMID- 1293774 TI - [Cause of death, survival, and prognostic factors in a series of 98 patients with chronic myeloid leukemia]. AB - PURPOSE: To analyse the survival from diagnosis to blastic crisis, as well as the causes of death and the significance of different features in patients diagnosed of chronic myelogenous leukaemia (CML). MATERIAL AND METHODS: The series includes 98 patients who died of CML in Asturias Central Hospital and other nearby hospital between 1970 and 1990. The CML diagnosis had been established according to conventional criteria. The blastic crisis was diagnosed in accordance with morphologic and cytochemical studies, complemented in some cases with the assay of TdT or other markers. The Kaplan-Meier curves and long-rank test were applied to the statistical analysis of survival. The prognostic factors were evaluated by univariate correlation. RESULTS: The series' mean age was 48.57 years (range: 6 90) and the M/F ratio was 56/42. Cytogenetic study had been performed in 35 patients, of whom 33 had the Ph' chromosome. Death occurred in the blastic crisis in 67 cases (72%), in the accelerated phase in 14 cases (15%) and in the chronic phase in 12 cases (13%). The cause of death could be determined in 47 cases; of them, 24 (51%) died of infection, 11 (23.4%) of haemorrhage, and the remaining 12 (25.6%) of different complications. The median survival of the group as a whole was 32 months (range: 4-137). For the blastic crisis this figure was reduced to 2.5 months (range: 1-14), the lymphoid forms doing better, 5 months, than the non lymphoid ones; 1.5 months (p < 0.03). Out of the data evaluated at diagnosis, only haemoglobin and the percentage of blast cells in peripheral blood showed any correlation with survival (r = +0.28, p < 0.05 for haemoglobin, and r = -0.30, p < 0.01 for blast cells). CONCLUSIONS: (1) Although most patients die from infection or haemorrhage during the blast crisis, CML increases the risk of death in the accelerated and chronic stages as well. (2) Non-lymphoid blastic crisis has poorer prognosis than the lymphoid form. (3) The concentration of blast cells and haemoglobin in peripheral blood at diagnosis acquire prognostic significance in the present study. PMID- 1293775 TI - [Normal values of hemoglobin, hematocrit, blood coagulation factors, and fibrinolysis in New Zealand white rabbits]. AB - PURPOSE: To assess the normal rates of several haematological parameters along with coagulation and fibrinolysis values. MATERIAL AND METHODS: Male white New Zealand rabbits weighting between 1.5 and 2.5 kg. were used in variable amounts for each test (117-102). The following haematological determinations were carried out: haemoglobin, haematocrit, platelet count, and peripheral blood cell morphology. Prothrombin time, kaolin-activated partial thromboplastin time and thrombin time were assessed as well. Fibrinogen, plasminogen, prothrombin, factor V, factor X and factor XIII assays were also performed, along with tests for fibrinolytic activity and assay of fibrin and fibrinogen degradation products. All tests were compared with samples of pooled human and rabbit plasma. A statistical study was carried out including mean, mode, standard deviation, variation coefficient, confidence interval and chi square test plus Kolmogorow Smirnoff test for normality assessment. RESULTS: The curves attained after plotting the figures for haematocrit, haemoglobin, platelet count, kaolin activated partial thromboplastin time, thrombin time and factors II and X approached the normal values (p > 0.05). Asymmetric curves were achieved for fibrinogen, prothrombin time and plasminogen (p < 0.005). Rabbit anti-fibrinogen serum reacted with rabbit plasma and fibrinogen, but failed to react against human samples. No fibrin and/or fibrinogen degradation products were detected and no fibrinolytic activity was observed on fibrin plate assays. CONCLUSIONS: White New Zealand rabbits have values for haemoglobin, haematocrit and fibrinogen similar to the human ones. On the contrary, factors V, X and XIII, along with plasminogen, are in higher concentration, especially the former. Factor II is present at about half the human concentration. No fibrinolytic activity could be demonstrated with the methods used here. PMID- 1293776 TI - [Effect of physical training on hematological parameters in young swimmers]. AB - PURPOSE: To evaluate the effects of a regular training programme on some haematological values in a group of young swimmers. MATERIAL AND METHODS: The study group is composed of 32 infantile swimmers (18 boys and 14 girls) and the control group of 12 boys and 11 girls of similar ages, performing no sports. Blood samples were taken at the beginning of training and four months later. Automated blood cell counts were performed in duplicate, along with assessment of the serum levels of iron, ferritin, transferrin and haptoglobin. The statistical study was made by comparison of means (Student's t, Wilcoxon and Mann-Whitney's U tests). RESULTS: Significant descent of haemoglobin rates (p < 0.05) was found in the swimmers, whereas serum iron was also significantly decreased (p < 0.01). Transferrin and haptoglobin were increased in both sexes (p < 0.01) in the swimmers, while ferritin was increased only in the female swimmers. With regard to the control groups, the boys showed significantly higher levels of ferritin both at the beginning and the end of the test, whereas the girls had lower only at the beginning (p < 0.01). CONCLUSIONS: After a 4-month physical training programme the tissular iron deposits are increased in a population of infantile swimmers, such increase being significant only in females. PMID- 1293777 TI - [Stereological study of the fat cells in bone marrows with a heterogeneous distribution of adipose tissue]. AB - PURPOSE: 1) To analyze to what extent the fat tissue fraction of the human bone marrow with heterogeneous distribution depends on size and number of adipocytes. 2) To infer the influence of local factors on the two aforementioned parameters. MATERIAL AND METHODS: The material was made up of 15 specimens of bone marrow biopsy with markedly heterogeneous distribution of fat tissue, alternating normal or hyperplastic zones (area I) with aplastic ones (area II). The method of study was the stereological technique on plastic-embedded specimen sections. RESULTS: In the area II, with a fat tissue fraction markedly higher than in area I, both adipocyte number and size were significatively increased. The fat tissue fraction difference (Dif FRGR) between both areas was significatively correlated with the difference of the adipocytes number (Dif Nv) but not of the size (Dif D). However, in multiple regression both Dif Nv and Dif D contributed significatively to Dif FRGR. CONCLUSIONS: Since the histopathological pattern investigated in this work represents a model caused by intervention of local factors, it can be concluded that these can modify both the size and number of adipocytes. PMID- 1293778 TI - [Treatment with interferon alfa-2a in the chronic phase of Philadelphia-positive chronic myeloid leukemia]. AB - PURPOSE: To evaluate the cytologic and cytogenetic response attained with interferon alpha-2a (IFN, Roferon*A) in patients with Ph '-positive chronic myelogenous leukaemia (CML) in the chronic phase. MATERIAL AND METHODS: A prospective study was carried out on 22 CML patients diagnosed in the Haematology Service at the Princesa Hospital in Madrid. The therapeutic regime consisted of two phases: A) Hydroxyurea was given until the white-cell count was reduced to 15 20 x 10(9)/L. B) Roferon*A was then given subcutaneously at a doses of 5 MU/m2 per day. The follow-up was performed weekly, and monthly once the leucocyte count had stabilized. The cytologic and cytogenetic response was assessed by bone marrow aspiration performed after 6, 9, 12 and 18 months. The toxicity was evaluated in accordance with the WHO recommendations. RESULTS: The median follow up is 263 days (21-930). Thirteen patients (65%) had initial complete haematological response and 3 (15%) had partial response. The mean time to achieve response was 42 days (0-321). In the last evaluation, 69% of the patients were in sustained haematological remission (53% complete and 16% partial) with median follow-up of 232 days (21-930). The cytogenetic response was evaluable in 13 patients (follow up > or = 6 months): three attained complete response (23%) and three others partial response (23%). The commonest untoward effects were hypertriglyceridaemia (100%) and myelosuppression (86%). Grade-III thrombocytopenia was seen in 19% of the patients and grade-III anaemia or leucopenia in 5%. No infectious or haemorrhagic complications have appeared. Therapy was discontinued in 3 patients (14%), two due to severe flu-like syndrome and one for parkinsonism after 809 days of treatment. At the moment of evaluation two patients had died, one in lymphoid blastic crisis on day 217 and the other in the immediate post-BMT period. CONCLUSION: Treatment with interferon-alpha 2A is useful in the chronic phase of CML. An important number of responses can be attained, even in patients in the late chronic phase, and the toxicity seems acceptable. PMID- 1293779 TI - [Neoplasias of the erythrocyte series and related clonal pathology. Unified view and proposal for classification]. PMID- 1293780 TI - [Rearrangement of the bcl1 and bcl2 oncogenes in chronic lymphoid leukemia]. AB - Oncogenes bcl1 and bcl2 are located in the rupture site of t(11;14) and t(14; 18), respectively. They have been found to rearrange in different B-cell malignancies. A molecular study of oncogenes bcl1 and bcl2 was carried out in 42 patients diagnosed of B-cell chronic lymphoid leukaemia. In 14.3% of the patients the rearrangement affected bcl1, but no differences were found with regard to stage and clinical course between these patients and those without any oncogen rearrangement. In all the patients studied bc12 was in a germinal configuration. PMID- 1293781 TI - [Masked Philadelphia chromosome: diagnostic implications in a case of chronic myeloid leukemia presenting in blast crisis]. AB - We present a female patient with acute non-lymphoblastic leukemia (ANLL) and with haematologic features suggestive of its evolution from chronic myeloid leukaemia (CML), in which a bone marrow karyotype showing a "masked" Philadelphia (Ph) chromosome due to a variant translocation of complex type t(9;9;22)(q32;q34;q11) was found. We comment the peculiarities of this special Ph chromosome as well as the differential diagnostic problems between ANLL Ph(+) and CML with onset in blastic crisis. PMID- 1293782 TI - [Correlation between the grade of histological malignancy and nuclear positivity using the AgNOR technique in 6 cases of isolated bone NHL]. AB - Several reports have shown that the degree of positivity for the AgNOR count can be used to evaluate the aggressiveness of malignancies since it express an increased protein-synthesis activity. This technique was applied to six cases of stage I osseous non-Hodgkin's lymphoma--4 intermediate grade (2 diffuse small, non-cleaved cell and 2 diffuse large, non-cleaved cell lymphomas) and 2 high grade immunoblastic lymphomas--in order to assess the histologic grade and the number of AgNOR-positive regions. It was noted that survival together with the trend to invade the surrounding soft tissues (i.e., the tumour aggressiveness) correlated with the AgNOR granule count. Both factors were also related with Ki 67 cell-proliferation antibody positivity. Such correlations were even higher than those found with the histologic features conventionally evaluated in the Working Formulation, so they seem to convey more reliable indices of neoplastic growth potential. PMID- 1293783 TI - [Chronic neutrophilic leukemia associated with myeloma. Simultaneous presentation]. AB - A case of chronic neutrophilic leukaemia associated with multiple myeloma is reported. The patient had a 6 months history of bruising and weight loss, and showed mature neutrophilic leukocytosis, hepatosplenomegaly, high neutrophil alkaline phosphatase score, hyperuricaemia, neutrophils with pseudotoxic granulation and scarce Dohle bodies; moreover, a monoclonal IgG lambda was detected amounting 57.3 g/L. The bone marrow was grossly hypercellular with marked myeloid hyperplasia and aggregates of immature plasma cells. After treatment during 1 year with melphalan and prednisone she is well, although persisting with neutrophilic leukocytosis, slight splenomegaly, and the monoclonal IgG decreased to 25.8 g/L. PMID- 1293784 TI - [Autotransfusion in the regional hospitals of Andalusia]. PMID- 1293785 TI - [Blood donation in persons older than 65 years]. PMID- 1293786 TI - [Cyclosporin-related coma in bone marrow transplantation]. PMID- 1293787 TI - [Translocation (4;11) associated with mature B-line acute lymphoblastic leukemia in an adult patient]. PMID- 1293788 TI - [Translocation T(2;9) in a patient with Philadelphia-negative chronic myeloid leukemia in blast crisis]. PMID- 1293789 TI - [Fever of unknown origin as the clinical manifestation of multiple myeloma activity]. PMID- 1293790 TI - [Pseudohyperphosphatemia in a patient with multiple myeloma]. PMID- 1293791 TI - [Sudden leukemization in a patient with a non-Hodgkin's lymphoma of a low grade of malignancy]. PMID- 1293792 TI - [Reduction of iron deposits after physical exercise of short-duration]. AB - PURPOSE: To study iron metabolism in young people subjected to short-term physical exertion. MATERIAL AND METHODS: Haemoglobin rate, plasma iron, total iron binding capacity and haptoglobin were assessed before, during and fifteen days after seven-day intensive exertions (military drill) in 38 cadets of the General Military Academy at Zaragoza, at sea-level altitude. The type and intensity of the exercises and the diet were similar for all the subjects. Mean and standard deviation of all values were calculated; the differences were studied by paired t test and p < 0.005 was fixed to allow statistical differences. RESULTS: Decreased serum ferritin, which probably means diminished iron deposits, was found after exertions. Haemolysis is not likely involved since the haptoglobin rates were not decreased below the security limits which avoid haemoglobinuria. CONCLUSIONS: Physical exercise, although of short duration, may lessen iron deposits, although not to the extent of iron-lack erythropoiesis. PMID- 1293793 TI - [Second neoplasms as a late complication of the treatment of Hodgkin's disease]. AB - PURPOSE: To determine the incidence of a second malignancy in patients with Hodgkin's disease (HD) diagnosed and treated in the same hospital. PATIENTS AND METHODS: A retrospective study was performed on 99 patients diagnosed and treated for HD in the Hospital San Carlos, in Madrid, between January 1976 and december 1987. The clinical records were revised; the diagnosis and staging followed the Rye and Ann Arbor criteria, and the treatment included radiation therapy (RT), chemotherapy (CT), or a combination of both. The diagnosis of the second malignancy was based upon clinical, analytical, radiological and histological records. RESULTS: The median age in the series was 31 years (16-82) and the M/F ratio was 61/38. The stage distribution was: I-9; II-29; III-31, and IV-30. Twenty-six patients received RT alone, 59 were treated with CT, and 14 received RT plus CT. A second neoplasm was found in 6 patients (6%), of whom 4 developed a myelodysplastic syndrome (MDS) and 2 a solid tumour. All the patients who had MDS had received MOPP or C-MOPP chemotherapy, associated in two of them with extensive RT. Both patients with solid tumour had been given CT+RT. The median time of presentation of the second malignancy since the diagnosis od HD was 89 months (48-174) for MDS and 120 months for the solid tumours. The four MDS patients have died, 2 for ANLL-M5, one for SRA and the remainder for cerebral haemorrhage, not yet evolved into acute leukaemia. The two patients which solid tumours are alive and seemingly in complete remission at 12 and 10 months, respectively, of the diagnosis of the second malignancy. CONCLUSIONS: 1) All the patients with second neoplasms had been previously treated with CT (MOPP or C MOPP) or CT+RT. 2) Non-Hodgkin's lymphoma has not appeared in any of the patients in this series. 3) An endless follow-up of patients with HD seems important in order to achieve an early diagnosis of other malignant complications which, although in case of MDS have poor prognosis, in case of solid tumours may do well with adequate treatment. PMID- 1293794 TI - [Disseminated intravascular coagulation induced by endotoxin in rabbits: effect of treatment with t-PA and urokinase]. AB - PURPOSE: To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit. MATERIAL AND METHODS: DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies. RESULTS: No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality. CONCLUSIONS: High-dose t-PA has beneficial effects on endotoxin induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model. PMID- 1293795 TI - [Acute lymphoblastic leukemias off therapy: course of 80 cases after treatment cessation]. AB - PURPOSE: To retrospectively analyse all the patients diagnosed and treated in the same hospital for acute lymphoblastic leukaemia (ALL) in whom therapy was suppressed after sustained complete remission (CR) for a variable period. PATIENTS AND METHODS: Eighty cases of ALL treated at the Jimenez Diaz Foundation between 1968 and 1991 were revised. Treatment had been suppressed after 60 months of maintained CR (1968-1974) or after 28 months (1986-1991), with a median follow up after suppression of 6 years. All the patients had been treated with several protocols (FJD-68, FJD/BFM, APO, BFM-83, BFM-86 and BFM-90). Maintained CR, relapses and course after therapy cessation were analysed. Actuarial curves of RC duration and survival were drawn according to the Cutler and Ederer life tables. RESULTS: The age at diagnosis ranged from 1.5 to 68 years. Childhood (< 15 years) ALL presented in 49 cases; 25 were young adults (15-30 years), and 6 others were over 30 years of age. Two of the 80 patients (2.5%) died in CR (astrocytoma and demyelinating leukoencephalopathy). Fifty-eight patients (72.5%) are living in maintained CR; 20 others relapsed (25%), 14 of them (70%) attaining a second CR. Allogenic BMT was carried out in 4 such cases. Four patients are out of any treatment after the second CR. The actuarial curves of CR duration after suppression of therapy gave a stable plateau at 73% for children, at 75% for young adults and at 22% for patients over 30 years. The survival after suppression of therapy showed a plateau at 75% for children and at 86% for young adults. CONCLUSIONS: 1) Relapse was seen in 25% of the patients after cessation of therapy. 2) Relapse occurred in the first two years after therapy cessation in 75% of the instances. 3) At this writing, 78.7% of the patients keep up the CR. 4) Adults over 30 years of age comprise the poorest prognosis. 5) The course of young adults in this series after cessation of therapy is as good as that of children. PMID- 1293796 TI - [Idiopathic thrombocytopenic purpura: present knowledge and future expectations]. PMID- 1293798 TI - [Hereditary elliptocytosis caused by a spectrin deficiency (Sp alpha I/46). 1st patient described in Cuba]. AB - We report biochemical studies of membrane proteins performed in a patient with hereditary elliptocytosis (HE). The presence of 90% of elliptocytes on wet smears of glutaraldehyde-fixed cells, the increased red cell thermal sensitivity, the normal erythrocyte membrane electrophoresis, the increased spectrin dimer in the 4 degrees C extract (35%) and the 46 Kd peptide present in electrophoresis after limited tryptic digestion of spectrin, allows us to classify this disorder as type I HE. The patient has common HE with compensated mild hemolysis. This is the first case of HE with alpha chain molecular variant of spectrin found in a Cuban population. PMID- 1293797 TI - [Use of a chromosome 21 gene library in the identification of a marker chromosome in chronic myeloid leukemia]. AB - The non-isotopic in situ hybridization makes it possible the analysis of, both, numeric and structural chromosome aberrations in interphase nuclei. Moreover, this technique is useful for identification of chromosome markers of unknown origin, frequently present in malignant diseases. In our case, the fluorescent in situ hybridization allowed us, in a CML patient in accelerated phase, to know the origin of a chromosome marker, and then, to state that the patient had a 21 trisomy added to the Philadelphia chromosome. PMID- 1293799 TI - [Appearance of a chronic myeloid leukemia in Waldenstrom's macroglobulinemia]. AB - Philadelphia chromosome-positive chronic myeloid leukaemia (CML) developed three years after the diagnosis of Waldenstrom macroglobulinemia (WM) in a patient who had received chlorambucil and prednisone during this time. Treatment with busulphan was started and two and a half years later the died in blastic crisis. Six months before the blastic transformation of the leukaemia the amount of IgM, which remains stable (above normal values) along the chronic phase, initiates a decrease, reaching normal values in the phase of acute transformation. CML is a very rare second neoplasia in patients receiving anticancer drugs. The correlation between the decrease of IgM and the blastic crisis is very interesting. We do not find an explanation for this finding although similar observations have been described heralding the appearance of second neoplasias in WM, and one might speculate with a possible role of IgM in the control of chronic phase of the myeloid leukaemia or if the overgrowth of blastic cells could overwhelm the development of lymphoplasmacytoid cells. PMID- 1293800 TI - [Advantages of a complete analytical study before the 1st blood donation]. PMID- 1293801 TI - Antonio Raichs lecture. Autologous bone marrow transplantation. PMID- 1293802 TI - [History--wear it with honor. Interview by Grethe Kjaergaard]. PMID- 1293803 TI - [Financial sector. Large purchasing power can act as oil on the water. Interview by Kirsten Stallknecht]. PMID- 1293804 TI - [Nursing story. My little recipe]. PMID- 1293805 TI - [Military psychiatry. You must be mentally ill, man]. PMID- 1293806 TI - [In vitro fertilization. A service for the childless]. PMID- 1293807 TI - [Waiting lists. ADP provides overview and better service]. PMID- 1293808 TI - [Waiting lists. Clear decisions in good time]. PMID- 1293809 TI - [Italy--no professional autonomy]. PMID- 1293810 TI - [French relief assistance--a way of life. Interview by Pia Loyau]. PMID- 1293811 TI - [French relief assistance--Doctors without Borders. Interview by Pia Loyau]. PMID- 1293812 TI - [Incontinence--testing of urinary condoms]. PMID- 1293813 TI - [Nursing story--I believe we shall survive]. PMID- 1293814 TI - [Executive Board. A broad but also vague work environment plan]. PMID- 1293815 TI - [Societal economy--economy seen through different glasses]. PMID- 1293816 TI - [AIDS--hemophiliacs' risk of dying before The European Human Rights Commission]. PMID- 1293817 TI - [French relief assistance--across all borders]. PMID- 1293818 TI - [Spain--bedside management. Interview by Kirsten Bjornsson]. PMID- 1293819 TI - [Spain--ideal and reality. Interview by Kirsten Bjornsson]. PMID- 1293820 TI - [Spain--for the competent. Interview by Kirsten Bjornsson]. PMID- 1293821 TI - [Nursing story. Ella's hidden world]. PMID- 1293822 TI - [Information to relatives--when patients isolate themselves. Interview by Grethe Kjaergaard]. PMID- 1293823 TI - [In the wings]. PMID- 1293824 TI - [Europe against cancer. Support from EEC could be returned]. PMID- 1293825 TI - [Cancer nursing. New continuing education for oncologic nurses]. PMID- 1293826 TI - [Australia--a study in health]. PMID- 1293827 TI - [Spain--nurses and family]. PMID- 1293828 TI - [The prospective dynamic observation of the pain syndrome in a population group selected at random]. PMID- 1293829 TI - [The side effects and complications in treatment with diuretic preparations. 2]. PMID- 1293830 TI - [The intoxication syndrome in acute dysentery]. PMID- 1293831 TI - [Herpetic infection in patients with lupus erythematosus]. PMID- 1293832 TI - [A case of the early development of ischemic heart disease in a female patient with dextrocardia]. PMID- 1293833 TI - [The development of signs of dilated cardiomyopathy in patients with nonobstructive hypertrophic cardiomyopathy]. PMID- 1293834 TI - [Food poisonings and diabetes mellitus]. PMID- 1293835 TI - [The clinico-immunological characteristics and treatment of acute intestinal infections caused by enterobacteria of the genus Citrobacter]. PMID- 1293836 TI - [The immunorehabilitative action of thymohexin in treating patients with chronic brucellosis]. PMID- 1293837 TI - [The dynamics of the levels of specific immunoglobins G, A, M and E during the treatment of patients with chronic brucellosis]. PMID- 1293839 TI - [Infectious diseases in the Russian Federation]. PMID- 1293838 TI - [The clinical manifestations of tropical malaria in local inhabitants and Europeans in the Republic of Guinea (Western Africa)]. PMID- 1293840 TI - [The clinical picture of acute viral hepatitis B and HLA antigens in women of reproductive age]. PMID- 1293841 TI - [The role of infectious antigens in the etiology of glomerulonephritis]. PMID- 1293842 TI - [Free-radical processes and lipid peroxidation in kidney diseases]. PMID- 1293843 TI - [Hyperlipoproteinemia as a factor in the progression of glomerulonephritis with nephrotic syndrome]. PMID- 1293844 TI - [Hemostatic disorders in lupus nephritis]. PMID- 1293845 TI - [The levels of antigens to plasminogen activators compared to their functional activity and inhibitor activity in patients with glomerulonephritis and amyloidosis]. PMID- 1293846 TI - [The endogenous phospholipase activity of the erythrocytes and the lipid peroxidation level in patients with chronic kidney failure]. PMID- 1293847 TI - [The effect of certain factors on the nature of the course and the rate of progression of chronic kidney failure in patients with kidney lesions of different etiologies (the results of the author's own long-term dynamic observations)]. PMID- 1293848 TI - [The comparative characteristics of parlodel, zinc sulfate and recombinant erythropoietin in treating uremic hypogonadism in patients on chronic hemodialysis]. PMID- 1293849 TI - [The biomedical aspects of the problem of intoxication in infectious pathology]. PMID- 1293850 TI - [Physiological approaches to the climatic treatment of kidney disease]. PMID- 1293851 TI - [Immunological criteria of the activity of glomerulonephritis]. PMID- 1293852 TI - [A comparative study of the plasma amyloid A level as well as of 9 other parameters in allograft rejection]. PMID- 1293853 TI - [Lupus subtypes--the relationship of the clinical and immunological signs]. PMID- 1293854 TI - [Systemic lupus erythematosus etiologically due to the hepatitis B and C viruses]. PMID- 1293855 TI - [The prevalence of systemic lupus erythematosus in Moldova]. PMID- 1293856 TI - [The clinical and immunomorphological characteristics of rheumatoid vasculitis]. PMID- 1293857 TI - [Sjogren's syndrome: some new facts]. PMID- 1293858 TI - Diffusion and focus in sexual networking: identifying partners and partners' partners. AB - This article describes the second stage of a research project on sexual networking that aims to further understanding of the spread of sexually transmitted diseases and HIV/AIDS in Ondo State, Nigeria. A sample of 488 males aged 15-50 were interviewed in depth to ascertain (1) the numbers and characteristics of their sexual partners, (2) the numbers and characteristics of the partners of those partners, and (3) the extent to which these relationships were commercial. In addition, a census was taken of all commercial sex establishments in order to estimate the numbers of their clients. The results show that male (and female) sexual networking is extensive, that in most nonmarital relationships men do not have accurate knowledge of their partners' partners, and that detailed questioning provides a reasonably accurate picture of the number of these relationships that are commercial in nature. The situation revealed was one of sexual diffusion rather than one with a strong focus on commercial sex workers, which fits the model of a slowly increasing HIV/AIDS epidemic rather than an explosive one. PMID- 1293859 TI - Contraceptive use in Matlab, Bangladesh in 1990: levels, trends, and explanations. AB - The results of a 1990 knowledge, attitudes, and practice survey in Matlab, Bangladesh, indicate that contraceptive prevalence has risen to 57 percent in the maternal and child health/family planning project area. Between 1984 and 1990 significant increases were registered in the proportions of women using contraceptives for the purposes of spacing and limiting births. By 1990 fertility control in the intervention area had become so widely diffused that educational differentials in contraceptive practice were no longer evident. Although significant gains in contraceptive use were also evident in the neighboring comparison area during this period, at 27 percent, prevalence there still remained substantially below the levels in the intervention area. The disparity in contraceptive use between the two areas is adequately explained neither by differences in socioeconomic conditions nor in the demand for family planning, but rather by differences in the intensity, coverage, and overall quality of their family planning programs. PMID- 1293860 TI - Changing men's attitudes and behavior: the Zimbabwe Male Motivation Project. AB - A multimedia communication campaign was conducted between 1988 and 1989 to promote family planning among men in Zimbabwe. The campaign consisted of a 52 episode semiweekly radio soap opera, about 60 motivational talks, and two pamphlets about contraceptive methods. Changes over time were measured by comparing a subset of a follow-up survey conducted from October to December 1989 to a baseline survey conducted from April to June 1988. Men exposed to the campaign were also compared to men who were not exposed. The follow-up survey revealed that the campaign reached 52 percent of men aged 18 to 55. Among married Shona-speaking men, use of modern contraceptive methods increased from about 56 percent to 59 percent during the campaign. Condom use increased from about 5 percent to 10 percent. Awareness and current use of modern contraceptives was also higher among men exposed to the campaign, primarily because of their greater awareness of condoms. Men exposed to the campaign were significantly more likely than other men to make the decision to use family planning and to say that both spouses should decide how many children to have. PMID- 1293861 TI - Evidence from peninsular Malaysia of breastfeeding as a contraceptive method. AB - This report examines Malaysian women's perceptions of the contraceptive effect of breastfeeding, the determinants of their perceptions, and any effect these perceptions might have on nursing duration and contraceptive use. The report also considers whether women are consciously replacing breastfeeding with modern contraceptive methods. Data from the 1976 Malaysian Family Life Survey are analyzed, and the author concludes that Malaysian women do perceive that breastfeeding has a contraceptive effect, but that this perception is not universal. Ethnicity and desire for a particular family size are the most significant determinants of this perception. Finally, Malaysian women's recognition of the contraceptive effect of nursing does not influence either the duration of their breastfeeding or their adoption of contraception. Malaysian women may not be abandoning breastfeeding to adopt contraception. More probably, breastfeeding declines and contraceptive prevalence increases with modernization. PMID- 1293863 TI - Setting standards of quality in family planning programs. PMID- 1293862 TI - An experiment using a month-by-month calendar in a family planning survey in Costa Rica. AB - Recent demographic surveys have incorporated a month-by-month calendar for the five-year reference period before the survey for the recording of fertility related events (sexual unions, contraceptive use, pregnancies, and breastfeeding). In the 1986 survey of Maternal and Child Health and Family Planning in Costa Rica, approximately one-half of the 3,527 women interviewed were administered a questionnaire with traditional fertility and family planning questions; the other half were asked virtually the same questions, but the women's responses were entered in a month-by-month calendar. The assignment of questionnaire type was randomly alternated by cluster. Comparisons of the number of events (live births, pregnancy losses, and contraceptive use) showed that more events were recorded among the women in the calendar group. Significantly less erroneous superposition of events (contraceptive use in the last trimester of pregnancy and hormonal contraceptive use in the first month postpartum) was noted when the calendar was used. PMID- 1293864 TI - Jordan 1990: results from the demographic and health survey. PMID- 1293865 TI - Transporter explosion: update on uptake. PMID- 1293866 TI - Development of the cytokine inducer romurtide: experimental studies and clinical application. PMID- 1293867 TI - Reinforcing drug seeking. PMID- 1293868 TI - How to estimate the total receptor concentration when the specific radioactivity of the ligand is unknown. AB - A computation method is presented allowing a direct determination of the total receptor concentration from a competitive displacement curve. Compared to the classical method based on the numerical processing of binding data, the proposed method has the advantage of being more accurate and of not requiring knowledge of the specific radioactivity of the ligand. PMID- 1293869 TI - The role of individual human cytochromes P450 in drug metabolism and clinical response. AB - Recent advances in the study of human cytochromes P450 by protein purification, molecular cloning techniques and analysis of polymorphisms has led to increased understanding of the role of the various forms in the metabolism of clinically important drugs. In particular, the substrate specificity of one form, CYP2D6, is well established. CYP2D6 shows polymorphism, with 5-10% of Caucasians (poor metabolizers) not expressing this enzyme. The molecular basis of this deficiency is now well understood and methods for the detection of poor metabolizers are discussed, as well as the effect of the polymorphism on drug metabolism. Substrate specificities and possible polymorphisms in other cytochromes P450 are also discussed. PMID- 1293870 TI - Neuroprotective role of adenosine in cerebral ischaemia. AB - Several lines of evidence suggest that adenosine may be an endogenous protective agent in cerebral ischaemia. Adenosine is normally present in the extracellular fluid in most tissues of the body, including the brain, and its level increases dramatically following hypoxia or ischaemia. The rate of adenosine production is enhanced when the energy demand is larger than the rate of energy supply. Adenosine acts on specific receptors that are present in most cells in the body and that produce cellular effects that tend to antagonize a number of pathological events thought to be instrumental for ischaemic nerve cell death. Karl Rudolphi and colleagues review evidence for the neuroprotective potential of adenosine and indicate some targets for drug development. PMID- 1293871 TI - [The structure and function of the chromosomal nucleolus organizer regions: the molecular, cytological and clinical aspects]. AB - Numerous data concerning nucleolar organizer region (NOR) structure and function in normal and pathological human cells are analysed. The contents of argentophilic nucleolar proteins vary in the cells tested. The silver-stained test is closely connected with cellular proliferative potentials and differentiation status of the cells. This test also depends on the level of tumor cell malignancy and seemed to be very useful for megakaryocyte and cardiomyocyte studies. In summary, the NOR silver-staining approach is of great value for both fundamental cytological investigations and wide medical practice. PMID- 1293872 TI - [The ultrastructure of the centrosome in cytoplasts and its alteration under the action of ouabain]. AB - It has been shown that after enucleation of the PE cells with cytochalasin D the centrioles remain in approximately 80% of cytoplasts. Some cytoplasts contain only single centriole, either a mother (active) of a daughter (inactive) one. 20% cytoplasts have no centrioles. 2h after enucleation the centrosome structure in the cytoplasts did not differ from that in normal cells. 14-16 h after enucleation in many cytoplasts large secondary lysosomes and lipid droplets appeared around the centrosome. At this time in some cytoplasts in the centrosome we observed free microtubule convergence foci. 14-16 h after the enucleation, some cytoplasts have doubling centrioles. Under the influence of ouabain (30 min), the number of active centrioles oriented perpendicularly to the substrate plane in the cytoplasts increased. We suggest that the preferentially perpendicular orientation of centrioles to the substrate plane does not depend on the nuclear activity. PMID- 1293873 TI - [The mitogenic effect of insulin isolated from the mammalian brain on Swiss 3T3 cells]. AB - Mitogenic properties of the insulin derived from pig brain were compared with the action of pancreatic (standard) pig insulin and epidermal growth factor (EGF) using the culture of Swiss 3T3 cells. The brain insulin, likely as the pancreatic insulin, induced uptake of 14C-thymidine by resting cells in a dose-dependent manner at concentration of 0.5-2.0 micrograms/ml in culture medium. However, at equal concentrations of these hormones the proliferating effect of the brain insulin appeared to be 2-fold higher than the effect of the pancreatic hormone. At the same time the mitogenic action of both hormones was lower than that of EGF (10 ng/ml). The additive effect of the brain insulin and EGF, administered in combination, was more pronounced than the effect of the pancreatic insulin combined with EGF. The data obtained suggest a possible participation of brain insulin in the process of nerve cell proliferation. PMID- 1293875 TI - [Endoplasmic reticulum (a review of the literature)]. AB - Recent data on the structural and molecular organisation of the endoplasmic reticulum (ER) are reviewed. A special attention is paid to the mechanism of soluble and integral membrane protein translocation across the ER bilayer. A model of phospholipid-coupled polypeptide translocation is introduced served to overcome hydrophobic and (or) conformational constraints during the passage of polar amino acid residues within a polar environment of the ER membrane. In addition the mechanisms of diverse covalent and noncovalent post-translocational polypeptide modifications are considered, together with the process of the sorting events among ER-resident polypeptides and those destined to leave the ER domain for the Golgi apparatus. PMID- 1293874 TI - [Growth factor from the tissues of the marine mollusk Mytilus edulis]. AB - The absence of specific stimulators of cell proliferation, i.e. of growth factors, is one of the causes of failure in long-term cultivation of the marine invertebrate cells. In search for such stimulators in tissues of marine invertebrates, we succeeded in discovering in some tissues a stimulator of cell proliferation, similar to EGF, with a comparatively high content of it in tissues of Mytilus edulis. The similarity of the obtained factor with EGF was shown by the substitution of 125I-EGF, connected with EGF receptors on the surface of A431 cells, with analysed extracts, as well as by the ability of this extract to induce the internalization of EGF-receptor complexes. The fraction of acid/ethanol extract of M.edulis stimulating the cell proliferation in resting mouse fibroblasts Swiss 3T3, was obtained in the same conditions as EGF did, using reversed phase chromatography. Thus, the factor from tissues of M.edulis may belong to the family of EGF-like factors. PMID- 1293876 TI - [The effect of the treatment of skin wounds in rats with hydrolytic enzymes on the synthetic activity of the epidermocytes]. AB - Epidermis cells synthetic activity was studied by a luminescent microscopy method. Different conditions of skin wound healing in intrascapular region were investigated on 84 rats-males. Daily effect of 0.2% trypsin or 0.1% ronidase solution on the healing surface for 20 min has been shown to increase basal layer cells synthetic activity of forming epidermis in comparison with control. However, maximum raise of epidermis cells functional activity after ronidase influence was observed already on the 4th day, while after trypsin action--only on the 7th. Epithelial cells synthetic activity decreases several days before total skin defect epithelialization. In all experiments their activity stabilizes not less than one month after the operation. We have come to a conclusion that the mechanism of healing acceleration due to proteolytic enzymes depends on basal layer cells synthetic activity of forming epithelium. PMID- 1293877 TI - [The characteristics of the internalization of normal and mutant receptors for the growth factor released by thrombocytes]. AB - The platelet-derived growth factor (PDGF) is a major mitogen in serum for connective tissue derived cells in culture. The influence of receptor structure on the ability of PDGF receptor to be internalized was studied using cell lines transfected with different PDGF-receptor constructions. CHO cell lines expressing either normal PDGF receptor (CHO wt cells) or truncated PDGF receptor, lacking all but 19 amino acids of the intracellular domain (CHO-ECTM cells) were stained according to the method of indirect immunofluorescence with monoclonal antibody B2 to PDGF receptor. It has been found that after a 30-min incubation of the CHO wt cells at 37 degrees C in the presence of PDGF-BB a typical process of endocytosis is observed, while after a 2 h incubation in the same conditions the staining of the cells is absent which suggested the existence of the down regulation and the process of degradation of PDGF receptor in CHO wt cells. In contrast, in the case of CHO-ECTM cells after both 30-min and 2-h incubation of cells in the presence of PDGF-BB a bright staining of margins and a low staining of the cytoplasm are observed. When the cells where incubated in the presence of lysosomotropic drug chloroquine (0.1 mM), that inhibits degradation of the receptor, the immunostaining of CHO wt cells is changed, with bright compact spots appearing. But in CHO-ECTM cells the fluorescence pattern is not changed. To examine the rate of endocytosis of PDGF-BB, both the types of cells were incubated in the presence of 2 ng/ml of 125I-PDGF-BB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293878 TI - [The antioxidant properties of tumor cell subpopulations]. AB - A study was made of the antioxidative activity (AOA), of the activity of glytathionreductase and catalase, and of SH-group concentration in suspensions of intact cells from eight fractions of the rat ascitic ovary tumor. A correlative bond was detected between AOA, the activity of antioxidative enzymes, and SH group concentration. It was shown that antioxidative properties of the fractions containing resting (G0) and polyploid cells were higher than those of proliferating diploid cells. PMID- 1293879 TI - [The cultivation of mouse and human lymphoid cells on serum-free media]. AB - The optimum composition of several serum-free media has been established for a long-term cultivation of hybridomas, lymphoid and erythroleukemic cells. The medium DME/F12 appeared to be the medium of choice. It is necessary to supplement the basic medium with lipid and iron transport proteins (bovine serum albumin, transferrin) and peptide hormone (insulin) for obtaining stable results. However, there are differences in successful growth of examined cell lines under serum free conditions: some of them acquire saturation density comparable with that of the control medium (hybridomas derived from myeloma Sp2/0-Ag14, cell lines K-562, Raji) but other lines do not (hybridoma derived from myeloma NS0/1, cell lines Namalwa, RPMI 1788, Molt-4). Thus, these serum-free media are not universal, therefore each new hybridoma and cell line should be tested to determine the suitability for them of some proposed media. The high effectiveness of cultivation under serum-free conditions can be presumably achieved by optimization of both qualitative and quantitative composition of the serum replacement and of the basic medium. PMID- 1293880 TI - [The effect of heavy metal salts on the embryonic development of the common frog]. AB - To elaborate methods of biological testing during monitoring of the environment, a study was made of the effect of heavy metal salts on frog embryos and of the influence of temperature on the extent of toxicity of these substances. It was shown that the early stages of embryogenesis were more sensitive to this toxic effect. The differences in the effect of heavy metals are expressed not only in the extent of toxicity, but also in the pattern of change in toxicity as related to concentration. A rise in temperature of the solution containing heavy metals results in a relative increase in the number of abnormal larvae, whereas a decrease in temperature of the solution leads to a higher mortality at the earliest stages of embryogenesis. The latter, apparently, is due to a longer duration of development at low temperature, and thus, to a longer exposure of embryos to toxic effect. This is more pronounced at earlier stages of development, more vulnerable (sensitive) to toxicants. The estimation of toxicity of a substance by the pathological changes induced in embryos and larvae is one of the most sensitive methods, which allows not only to determine the extent of toxicity, but also to give prognosis of its possible effect on the population. PMID- 1293882 TI - Transport of malic acid in the yeast Schizosaccharomyces pombe: evidence for a proton-dicarboxylate symport. AB - The transport system for malic acid present in Schizosaccharomyces pombe cells, growing in batch culture on several carbon sources, has been studied. It was found that the dicarboxylic acid carrier of S. pombe is a proton-dicarboxylate symporter that allows uphill transport and accumulation as a function of delta pH with the following kinetic parameters at pH 5.0: Vmax = 0.1 nmol of total malic acid s-1 mg (dry weight) of cells-1 and Km = 1.0 mM total malic acid. Malic acid uptake (pH 5.0) was accompanied by disappearance of extracellular protons, the uptake rates of which followed Michaelis-Menten kinetics as a function of the acid concentration. The Km values calculated as the concentrations either of anions or of undissociated acid, at various extracellular pH values, pointed to the monoanionic form as the transported species. Furthermore, accumulated free acid suffered rapid efflux after the addition of the protonophore carbonyl cyanid m-chlorophenyl hydrazone. These results suggested that the transport system was a dicarboxylate-proton symporter. Growth of cells in a medium with glucose (up to 14%, w/v) and malic acid (1.5%, w/v) also resulted in proton-dicarboxylate activity, suggesting that the system, besides being constitutive, was still active at high glucose concentrations. The following dicarboxylic acids acted as competitive inhibitors of malic acid transport at pH 5.0: D-malic acid, succinic acid, fumaric acid, oxaloacetic acid, alpha-ketoglutaric acid, maleic acid and malonic acid. In addition, all of these dicarboxylic acids induced proton movements that followed Michaelis-Menten kinetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1293881 TI - Effect of sterol alterations on conjugation in Saccharomyces cerevisiae. AB - Sterol auxotrophic strains of Saccharomyces cerevisiae were grown and allowed to conjugate on media supplemented with various sterols. The mating efficiency of the auxotrophs is perturbed by the replacement of the normal yeast sterol, ergosterol, with other sterols. After 4 h of mating, cells grown on ergosterol exhibited a 30-fold higher productive mating efficiency than those cells grown in stigmasterol. Aberrant budding by the conjugants was enhanced following incubation on stigmasterol and other non-ergosterol sterols. Using light and electron microscopy, we demonstrated that there is a reduced ability for stigmasterol-grown cells to undergo cytoplasmic fusion during conjugation. Many of the mated pairs remained adherent but prezygotic even after 12 h of incubation. The addition of ergosterol to cells previously grown on stigmasterol rescued the organisms, allowing for zygote formation and normal budding. PMID- 1293883 TI - Polyamines and cell wall organization in Saccharomyces cerevisiae. AB - Cells of Saccharomyces cerevisiae 179-5, an ornithine decarboxylase mutant (spe 1), showed several ultrastructural abnormalities when cultivated in the absence of polyamines. Besides the appearance of microvacuole-like spaces in the cytoplasm and of deformed nuclei, the most important alterations seemed to be located in the cell wall, which was thicker and of heterogeneous texture, and in the cell membrane, of irregular contour. These modifications could not be evoked by general stress conditions elicited by lack of nutrients. The relative levels of cell wall polysaccharides were altered in polyamine-deprived organisms, giving an envelope with increased mannan and decreased glucan content; this cell wall was incompletely attacked by the lytic enzyme zymolyase. Polyamine depletion led also to some abnormalities in the budding pattern. The above observations suggest the involvement of polyamines in the correct structure and organization of the yeast cell. PMID- 1293884 TI - Fluorocytosine causes uncoupled dissipation of the proton gradient and behaves as an imperfect substrate of the yeast cytosine permease. AB - At pH 5-6 ATP-depleted washed cell preparations of strain NC233-10b[pII4-9], in which the cytosine permease was overexpressed, absorbed cytosine, hypoxanthine or fluorocytosine stoichiometrically with, respectively, about 1, 1.4 and 5 proton equivalents. The cellular pH fell proportionately. The membrane depolarization caused by each compound was assayed in the presence of glucose with a voltage sensitive dye and increased in the same order. Fluorocytosine significantly lowered the growth yield that a 'petite' strain of the yeast formed at limiting glucose concentrations. At pH 5.6 with extracellular [K+] below 1 mM, each of the three substrates was accumulated about 200-fold from a dilute solution at the expense of the proton gradient. This concentration ratio corresponds to a solute gradient (delta mu(s)) of 13 kJ mol-1. Raising [K+]o systematically lowered the substrate accumulation ratio and delta muH. The mean ratio delta mu(s)/delta muH was 0.82 for all three substrates. It was concluded that whereas the behaviour of cytosine approximated to that expected for a symport of unit proton stoichiometry, the absorption of protons with fluorocytosine and, to a lesser extent, hypoxanthine, was only partly conserved as useful work. A possible mechanism of this novel phenomenon is outlined. PMID- 1293885 TI - DNA transformations of Candida tropicalis with replicating and integrative vectors. AB - The alkane-assimilating yeast Candida tropicalis was used as a host for DNA transformations. A stable ade2 mutant (Ha900) obtained by UV-mutagenesis was used as a recipient for different vectors carrying selectable markers. A first vector, pMK16, that was developed for the transformation of C. albicans and carries an ADE2 gene marker and a Candida autonomously replicating sequence (CARS) element promoting autonomous replication, was compatible for transforming Ha900. Two transformant types were observed: (i) pink transformants which easily lose pMK16 under non-selective growth conditions; (ii) white transformants, in which the same plasmid exhibited a higher mitotic stability. In both cases pMK16 could be rescued from these cells in Escherichia coli. A second vector, pADE2, containing the isolated C. tropicalis ADE2, gene, was used to transform Ha900. This vector integrated in the yeast genome at homologous sites of the ade2 locus. Different integration types were observed at one or both ade2 alleles in single or in tandem repeats. PMID- 1293886 TI - DIT101 (CSD2, CAL1), a cell cycle-regulated yeast gene required for synthesis of chitin in cell walls and chitosan in spore walls. AB - A mutant screen has been designed to isolate mutants in Saccharomyces cerevisiae deficient in spore wall dityrosine. As shown by electron microscopy, most of the mutant spores lacked only the outermost, dityrosine-rich layer of the spore wall. Mutant dit101, however, was additionally lacking the chitosan layer of the spore wall. Chemical measurements showed that this mutant does not synthesize chitosan during sporulation. The mutant spores were viable but sensitive to lytic enzymes (glusulase or zymolyase). Unlike most of the dit-mutants, dit101 did show a distinctive phenotype in vegetative cells: they grew normally but contained very little chitin and were therefore resistant to the toxic chitin-binding dye, Calcofluor White. The cells showed barely detectable staining of the walls with Calcofluor White or primulin. The decrease in the amount of chitin in vegetative cells and the absence of chitosan in spores suggested that the mutant dit101 could be defective in a chitin synthase. Indeed, a genomic yeast clone harboring the gene, CSD2, sharing significant sequence similarity with yeast chitin synthases I and II (C. E. Bulawa (1992), Mol. Cell. Biol. 12, 1764-1776), complemented our mutant and was shown to correspond to the chromosomal locus of dit101. Thus, the mutations dit101 and csd2 (and probably also call; M. H. Valdivieso et al., (1991), J. Cell Biol. 114, 101-109) were shown to be allelic. The gene was mapped to chromosome II and was located about 3 kb distal of GAL1. Using this DNA clone, a transcript of about 3500-4000 nucleotides was detected. Comparing RNA isolated from vegetative cells and from sporulating cells at different times throughout the sporulation process, no significant differences in DIT101 transcript levels could be detected indicating absence of sporulation specific transcriptional regulation. However, the amount of DIT101 transcript changed significantly at different stages of the mitotic cell cycle, peaking after septum formation, but before cytokinesis. As most of the chitin synthesis of vegetative cells occurs at this stage of the cell division cycle, chitin synthesis mediated by DIT101 could be primarily regulated at the level of transcription in vegetatively growing cells. PMID- 1293887 TI - Genetic and physical mapping of the WBP1 locus close to CENV. AB - The WBP1 locus, encoding an essential component of the N-oligosaccharyl transferase, was mapped both genetically and physically. The gene is located on chromosome V between CENV and gcn4. The distance from CENV sequences is 2 kb. PMID- 1293888 TI - The allantoin and uracil permease gene sequences of Saccharomyces cerevisiae are nearly identical. AB - We have determined the structure of the allantoin permease (DAL4) gene of Saccharomyces cerevisiae. The gene putatively encodes a hydrophobic protein with a M(r) of 71,755. It possesses the alternating hydrophobic-hydrophilic regions similar to those found in many other integral membrane proteins. The most striking feature of the allantoin permease component encoded by DAL4 is its striking similarity to the uracil permease component encoded by FUR4. Although data available indicate that these proteins do not share any overlap of function, their predicted protein sequences are 68% identical, 81% similar, and their DNA sequences are 70% identical. The upstream regulatory region of DAL4 contains all of the characterized cis-acting elements previously reported for inducible allantoin pathway genes: six sequences homologous to UASNTR, the element responsible for nitrogen catabolite repression-sensitive activation of allantoin pathway gene expression, and two sequences homologous to the cis-acting element responsible for inducer-responsiveness of the allantoin pathway genes, UIS. The finding of these homologous sequences predicted to exist on the basis of DAL4's expression characteristics, supports and strengthens the suggestion that these elements mediate the functions we have previously ascribed to them. PMID- 1293890 TI - The effect of an experimental neoplastic disease on the flux of sodium and potassium ions across red blood cells and on the lipid composition of their membranes. AB - The erythrocytes from Morris Hepatoma 5123 bearing rats took up Na+ and K+ ions from the incubation medium and released Na+ into the extracellular space at lower rates than did erythrocytes from intact control rats. The lipid composition of erythrocytes membranes from the tumor-bearing rats differed from that of membranes from unaffected rats, showing increased contents of phospholipid phosphorus and a decreased content of cholesterol, resulting in decreased cholesterol:phospholipid molar ratios. PMID- 1293889 TI - A simple method for visualization of phenolics exudation by roots of intact lupin plants; the effect of nitrate and pH. AB - Phenolics exudation by imbibed seeds and roots of intact lupin plants (Lupinus albus L.) was studied during the first 4 days of growth by a new agar test with specific reagents for phenolics (Gibbs reagent, Naturstoffreagenz A). Comparative studies of the phenolics exudation reveal that legumes exude different phenolics (even if not qualitatively, then at least quantitatively) than oat. The exudation of phenolics starts very quickly after the imbibition of seeds and can be visualized as early as 24 h after sowing. In older seedlings, the exudation of phenolics can be detected along root zones and is influenced by nitrate and pH. At acidic pH, nitrate reduces phenolics exudation, but at pH 7.5 the exudation of phenolics becomes restricted to only some root zones. Nitrate must be present in the rooting media for at least 24 h to cause visible changes in the pattern of exudation at different pH values. PMID- 1293891 TI - Effect of mesitylene on ethanol metabolism in rat liver microsomes. AB - Increased catalase activity was observed in the liver microsomal fraction of ethanol-treated rats (10% v/v aqueous ethanol solution per os for 5 weeks). In contrast, cytochrome P-450 concentration and specific activity of NADPH cytochrome c reductase remained at the same level as in the liver of control rats (drinking water). The ratio of microsomal H2O2-generation to catalase activity was lower in the "ethanol" group than in the control one. This phenomenon seems to be related to the increased contribution of the "peroxidatic" reaction (increased rate of ethanol oxidation). Administration of mesitylene (1,3,5 trimethylbenzene) by gastric tube for 3 days (5 mmoles per kg daily) increased cytochrome P-450 concentration, specific activity of NADPH-cytochrome c reductase and ethanol metabolism. PMID- 1293892 TI - On the possibility of involvement of glutamate:glyoxylate and serine:glyoxylate aminotransferases from rye (Secale cereale L.) seedlings in the metabolism of tetrapyrrole compounds. AB - The activity of highly purified L-serine:glyoxylate aminotransferase (SGAT, EC 2.6.1.45) from rye seedlings was inhibited competitively by 5-aminolevulinate (ALA, Ki = 5 mM) SGAT was activated by hematin. Protoporphyrin IX and hematin inhibited irreversibly the activity of highly purified glutamate:glyoxylate aminotransferase (GGAT, EC 2.6.1.2) from rye seedlings. SGAT was found to catalyse transamination between ALA and hydroxypyruvate, whereas GGAT that between ALA and 2-oxoglutarate or pyruvate. It is suggested that SGAT is involved in the process of degradation of the excess ALA which has not been incorporated into porphyrin compounds. PMID- 1293893 TI - Prediction of protein secondary structure by neural networks: encoding short and long range patterns of amino acid packing. AB - A complex, cascaded neural network designed to predict the secondary structure of globular proteins has been developed. Information about the local buried-unburied pattern and the average tendency of the particular types of amino acids to be buried inside the globule were used. Nonspecific information about long distance contact maps was also employed. These modifications result in a noticeable improvement (3-9%) of prediction accuracy. The best result for the average success ratio for the testing set of nonhomologous proteins was 68.3% (with corresponding Matthews' coefficients, C alpha,beta,coil equal to 0.60, 0.47, 0.43, respectively). PMID- 1293895 TI - Negative effect of stress of in vitro fertilization program on quality of semen. AB - There are controversial data on the effects of stress on semen quality during treatment for infertility. We have compared the parameters of semen obtained from 84 patients on the day of the ovocyte pick-up during an in vitro fertilization and embryo transfer program (IVF) with those of semen collected from the same patients on the day of admission to the program (up to 3 months earlier). Abnormal semen has been found in 2 of the 84 patients on the day of admission and in 11 on the day of IVF. There were no improvements in semen quality of any patient at the second test. All except two parameters evaluated objectively by the Hamilton-Thorn Motility analyzer were significantly worse (p < 0.001) on the day of IVF, the exceptions were the percentage with moderate or slow motility and the Linear Index. These data indicate that the emotional stress to a subject enrolled in an IVF program negatively affects the quality of semen. Some suggestions are made for improved management of these patients. PMID- 1293894 TI - Luteal phase defects in assisted reproduction: the role of luteal phase supplementation. AB - Data from literature show that whereas in non-GnRH-a controlled ovarian hyperstimulation cycles luteal phase supplementation is not crucial, its use in GnRH-a/gonadotropins protocols seems to lead to a definite reduction of the negative effects of such drugs. The most important side effect of the hCG use as luteal support is the increased rate of the ovarian hyperstimulation syndrome (OHSS). Therefore its use should be reserved for very selected patients, for those subjects with preovulatory levels of E2 < 2500 pg/ml. As regard the use of progesterone, most authors agree that it has less efficacy than hCG but this depends on the administration route. PMID- 1293896 TI - Conservative treatment of ectopic pregnancy with intramuscular administration of methotrexate (MTX/CV). AB - 20 cases of unruptured ectopic pregnancies were studied from August 1990 till May 1991. They were treated according to the Sauers et al. (1987) protocol with Methotrexate and rescuvolin. The treatment was successful in all but one case. Six out of 17 cases had a normal pregnancy in the 12 months following treatment. Seventeen out of 20 cases had tubal patency checked with HSG and laparoscopy. We conclude that conservative management of unruptured pregnancy with MTX must be the treatment of choice. PMID- 1293897 TI - Presurgical treatment of uterine fibroids by using gonadotropin-releasing hormone agonists. AB - Evaluation of clinical intra- and post-operative benefits of pre-myomectomy therapy with a Gonadotropin-Releasing Hormone Agonist (GnRH-A) (Goserelin) in anemic and non-anemic patients suffering from uterine leiomyomas. Evaluation of ultrasound, estradiol (E2) and hematological measurements before and during treatment with a GnRH-a in thirty women with uterine leiomyomas, comparing pre treated patients operative time, total intraoperative blood loss, blood counts and febrile morbidity with of thirty-five control women. GnRH-A pre-treatment cures, iron-deficiency anemia, significantly reduces myoma and uterine volume (p < 0.01), total intra-operative blood loss (p < 0.001), decreases post-operative febrile morbidity, though it does not reduce operative time. GnRH-A pre-treatment over a period no longer than two months should be suggested in anemic patients suffering from uterine leiomyomas who have to undergo myomectomy. PMID- 1293899 TI - Successful pregnancy in a pure gonadal dysgenesis with karyotype 46,XY patient (Swyer's syndrome) following oocyte donation and hormonal treatment. AB - A pregnancy obtained in a patient with 46XY gonadal dysgenesis (Swyer's syndrome) after ovum donation and IVF/ET is described. The efficacy of this technique in overcoming particular cases of otherwise irreversible infertility is discussed. PMID- 1293898 TI - Flutamide: a rational approach to hirsutism. AB - The Authors would show the effectiveness of flutamide, a potent selective antiandrogen, by an analysis of 30 patients with moderate to severe hirsutism. This therapy caused a marked improvement of clinic symptoms. PMID- 1293900 TI - Sodium and potassium in normal and pathological seminal plasma. AB - A total number of 273 seminal plasma samples from normozoospermia (n = 91), oligozoospermia (n = 50), oligo-asthenozoospermia (n = 76), asthenozoospermia (n = 10) and azoospermia (n = 46) were analysed for sodium and potassium. A decreased sodium level was seen in pathological groups. A negative correlation was found to be in existence between sodium and potassium in seminal plasma in the groups studied except in azoospermia. Positive correlation was found between sodium and motile spermatozoa in normal and oligozoospermia. In oligo asthenozoospermia it was negative. Potassium, was negatively correlated with percentage of motile spermatozoa in the groups studied. PMID- 1293902 TI - [The polymerase chain reaction (PCR) and its application in transfusion medicine and hematology]. AB - The new technique, polymerase chain reaction, used for in vitro DNA fragments amplification is described. The conditions of the reaction and methods of data analysis are discussed as well as the usefulness of this technique in research and medical practice. PMID- 1293901 TI - "In vitro" tests to assess human sperm fertilizing ability. PMID- 1293903 TI - [Advances in treatment of multiple myeloma]. AB - Median survival time in multiple myeloma treated with melphalan and prednisone does not differ significantly from survivals yielded by combination of alkylating cytostatics. Intensive chemotherapy linked with marrow transplantation provides elongated complete remission more frequently in patients, who reached early remission by conventional means. Multidrug resistance of myeloma plasmocytes has been overcome by adding of verapamil to the VAD program. In recently diagnosed myelomas, it is more rational to assay the survival prognosis and access to intensive therapy. PMID- 1293905 TI - [Activity of NK in elderly people]. AB - Optimally healthy elderly persons, selected according to Senior Protocol criteria, aged 60-93 years were characterized by as high level of NK activity as their young adult, 20-35 years old, counterparts. NK activity of the nearly optimally healthy elderly persons of the corresponding age was significantly lower than that of optimally healthy ones. The lowest values of NK activity were noted for the elderly persons suffering from recurring infections of the respiratory tract. PMID- 1293904 TI - [Evaluation of microtest in dextran gel for blood group serology]. AB - Microtest in gel was compared to the traditional, immunohaematological methods. Blood samples of 1.032 persons were tested. From the results presented in this paper we conclude that Gel-test is specific, clear, easy to perform and more sensitive than the traditional methods. It can be used for red cell phenotyping and antibody detection as well. By this technique it was possible to establish the specificity of antibodies of Rh system not found by any other method. The advantage of this test is that nearly all unspecific reactions could be eliminated. The disadvantage concerned the high sensitivity in the detection of cold, clinically insignificant allo- and autoantibodies. Therefore, some modifications for the elimination of these unfavourable reactions were introduced. PMID- 1293906 TI - [Evaluation of phagocytic activity of peripheral blood neutrophils in patients after kidney transplantation treated with cyclosporin and prednisone or with azathioprine with prednisone]. AB - In 32 renal transplant patients neutrophil phagocytic activity was evaluated using living bacterial cells of Staphylococcus aureus Oxford 209 P strain. The total group of patients was divided into two subgroups according to the kind of the applied immunosuppressive treatment 1) cyclosporin--12 patients treated with cyclosporin A along with prednisone and 2) azathioprine--20 patients treated with azathioprine along with prednisone. The index of phagocytizing cells i.e. the percentage of neutrophils phagocytizing the bacterial cells was assessed in the investigation of phagocytosis. In the renal transplant patients as compared with the control group, statistically significant increase in the phagocytic of peripheral blood neutrophils in relation to the used bacterial cells of Staphylococcus aureus Oxford 209 P strain was found. Statistically significant differences in the investigated range were also present between the compared subgroups. In the cyclosporin subgroup statistically significant increase was revealed in the percentage of phagocytizing neutrophils. PMID- 1293907 TI - [Clonal proliferation of less mature granulocytic precursors (CFU-dG) under the influence of neoplastic B lymphocytes in low grade non-hodgkin's lymphomas]. AB - The effect of peripheral blood lymphoma B cells from low grade malignancy non Hodgkin's lymphoma patients (Kiel classification: lymphocytic, centrocytic, centroblastic-centrocytic lymphomas) on clonal growth of normal marrow granulocytic precursors (CFU-dG) was studied. Using in vivo diffusion chamber culture method it was shown that all the tested lymphoma cells enhanced the CFU dG growth by releasing humoral factor(s). The effect of stimulation was cell concentration and cell-source dependent. The colony stimulating activity produced by centrocytic lymphoma cells had higher potency than that released by centroblastic-centrocytic lymphoma cells, whereas lymphocytic lymphoma cells showed the lowest ability to generate the CFU-dG growth-promoting activity (p < 0.01). It was shown that the CFU-dG growth enhancing effect was independent of marrow-derived macrophages and T lymphocytes (p > 0.05). Normal peripheral blood B lymphocytes used as a control did not show any substantial effect on the granulocytic precursors proliferation. PMID- 1293908 TI - [Effect of thrombin stimulated blood platelets on plasma fibrinolytic activity]. AB - The influence of thrombin stimulated-blood platelets on plasma fibrinolytic activity was evaluated. Thrombin-activated blood platelets have been shown to significantly inhibit plasma fibrinolytic activity before and after venous stasis. This was expressed by a reduction of the digestion area of fibrin dish from 10.3 +/- 3.3 cm2 to 3.7 +/- 1.5 cm2 and from 15.6 +/- 6.8 cm2 to 3.7 +/- 1.7 cm2, respectively. PMID- 1293909 TI - [Acute nonlymphoblastic leukemia as a secondary malignancy--demonstration of 15 patients]. AB - Among 90,128 patients with malignancies in the years 1976-1989 acute non lymphoblastic leukaemia (ANLL) was diagnosed in 351 patients (0.4%) and in 15 (4.3%) of them ANLL was secondary neoplasm. Secondary ANLL occurred in 10% of all the 148 secondary malignancies observed at that period of time and constituted 6.7% of secondary malignancy in patients with solid tumours and 43% in patients with myeloproliferative syndromes as a first malignant neoplasm. In the treatment of first malignancy radiotherapy was applied in 11 persons, in combination with chemotherapy in 7 of them and chemotherapy alone was given to 4 patients. The appearance of the secondary ANLL was usually preceded by the myelodysplastic syndrome. Morphologically, secondary ANLL belonged mostly to M6 and M4 (8 patients) according to FAB classification. The course of ANLL was fulminant and the disease was completely resistant to the treatment. PMID- 1293910 TI - [Comparative evaluation of treatment results in advanced multiple myeloma with the help of polychemotherapy with vincristine, doxorubicin, dexamethasone (VAD) or only with dexamethasone]. AB - A prospective clinical trial was undertaken to determine the therapeutical effectiveness of multidrug chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) or only high dose of dexamethasone (D) in 56 patients with multiple myeloma (MM). The group of patients included 41 with intermediate (II) and 15 with high (III) tumor mass. The final evaluation was performed in 19 patients treated with D and in 19 receiving VAD regimen. Improvement was defined by at least 50% reduction of serum myeloma protein concentration or disappearance of light chain proteinuria. The VAD regimen was more effective giving improvement in 90% of patients with no prior therapy and in 44% of patients with reflectory myeloma. In this respect, cytoreduction of the same magnitude was noted both in stages II and III. Higher therapeutical effect of VAD regimen was observed independently of the immunological type of MM. The treatment with D has given the improvement in 56% of patients with no previous therapy. Our results support the usefulness of VAD regimen in MM-patients with no prior therapy and with refractory myeloma. High frequency of therapy-related complications, however, indicates that VAD treatment should rather be reserved for the patients with resistant MM. PMID- 1293911 TI - Leprosy in HIV-positive and syphilitic young Paraguayan man. AB - In a borderline lepromatous patient a positive serology for syphilis and HIV 1 has been detected. The patient also had an urinary tract infection with Acinetobacter calcoaceticus. In Paraguay up till now no leprosy cases infected with HIV have been reported. PMID- 1293912 TI - [Cutaneous neoplasms during leprosy: 2 case reports]. AB - The authors report on two cases of dermal neoplasia in foot trophic disorders observed in leprous subjects. The report includes the description of the clinic and histologic data as well as the surgical technique used; finally, it underlines the importance of a precocious diagnostic so as to obtain a good therapeutic result. PMID- 1293913 TI - [Leprosy serology: current status and perspectives]. AB - The different serological tests used for leprosy are firstly the methods for the detection of antibodies (anti-PGL1, 35kD, 36kD, LAM), and secondly, the tests to detect the PGL1 antigen from the serum or urine. The antibody detection tests have a good but insufficient specificity for the diagnosis of leprosy patients and their sensitivity is generally high for the multibacillary patients but low for the paucibacillary patients. Their positive predictive value for the diagnosis of patients in a population are very low: 2.1% for the anti-PGL1 ELISA when the prevalence is 1/1000. For the early diagnosis of patients and the follow up of high risk populations, these tests are not cost effective: the number of patients detected in these populations is 10 fold lower than in the general population and the relative risks for developing the disease are not different among seropositive and among seronegative groups. In treated multibacillary patients, the IgM anti-PGL1 level decreases in correlation with the decrease of the bacillary index. For the diagnosis of M. leprae infection in a population, there was no correlation between the anti-PGL1 seroprevalence and the prevalence of the disease. Concerning the PGL1 antigen detection tests, they are specific and sensitive for the diagnosis of multibacillary patients but they cannot be used in routine for technical reasons. In conclusion and to date, the usefulness of serological tests in a leprosy control programme is quite questionable. PMID- 1293914 TI - [Leprosy survey conducted in the Central African Republic from 1982 to 1985 among the Ba-Benzele Pygmies]. AB - A leprosy survey was conducted from 1982 to 1985 among 2650 semi-sedentarized Pygmies in two camp-villages in the Central African Republic. Leprosy is endemic there, with an estimated prevalence rate of 1.05% and an annual detection rate of 0.2%. In view of its close relations with other neighbouring ethnic groups this Pygmy community can be considered as a target population the study of which provides indications on the transmission and typical course of leprosy in the region and also as a potential focus of contamination. However, the concurrent presence of endemic tuberculosis made it necessary during the survey to look for clinical associations of leprosy and tuberculosis in patients so that the standard multidrug treatment schedules comprising rifampicin could be adjusted accordingly. PMID- 1293915 TI - Histological changes with combined chemotherapy and immunotherapy in highly bacillated lepromatous leprosy. AB - Highly bacillated untreated lepromatous cases with an initial BI 4+ of to 6+ were treated with combined multidrug treatment (MDT) and immunotherapy with heat killed Mycobacterium w or BCG. The vaccines were administered intradermally every six months. It was observed that majority of cases on immunotherapy showed increased lymphocytic infiltration (both at local and distant sites) and some cases showed epithelioid cells as well. The lymphocytic infiltration was (slightly) more vigorous in those vaccinated with Mycobacterium w. Such changes were not seen in the patients on MDT alone. Also, the granuloma fraction reduced much faster in cases who were on additional immunotherapy as compared to those on MDT alone. These changes along with evidence of clinical and bacteriological improvements suggest that immunotherapy may have an important supportive role specially in the therapy of anergic lepromatous cases. PMID- 1293916 TI - Treated-cured indeterminate leprosy: a search for predictive histopathological and immunohistochemical parameters in skin biopsies taken from patients at admission and at clinical discharge. AB - In a previous study an index (sigma 3) resulting from the summation of three parameters, i.e., presence of bacilli, even in small numbers, in various dermal structures, multiple positive antigen sites as detected by anti-BCG antiserum and dermal nerve involvement, identified 72.22% of cases of indeterminate leprosy which progressed to multibacillary leprosy. The present study was undertaken to investigate possible parameters which might be indicative of indeterminate leprosy which would persist unchanged or be cured (treated cured patients). Thirty treated cured indeterminate leprosy patients were selected from the files of the Sao Paulo Health Institute and studied by histopathological, immunohistochemical and statistical methods similar to those employed in the previous study. The sigma 3 index was 4.10 +/- 0.60, a finding that places this group of patients in a position close to that of patients changing to paucibacillary leprosy but statistically different from that of patients progressing to multibacillary leprosy. Moreover, it was found that patients belonging to this group have heterogeneous single parameters, some of them suggestive of multibacillary and others of paucibacillary leprosy. Immunologically based techniques mainly employing rabbit anti-BCG serum as the primary antibody have proved to be valuable to detect antigen sites in biopsies from indeterminate leprosy patients and should be used together with the bacillary index during the follow up and clinical discharge control of such patients. In the present study, we show that clinical discharge of these patients did not mean a complete clearance of bacillary antigens. PMID- 1293917 TI - [Effects of tetraethylammonium chloride and verapamil on the effective refractory period of ischemic myocardium in rabbits]. AB - The effects of potassium ion channel blocker TEA and calcium ion channel blocker verapamil on effective refractory period (ERP) of ischemic ventricular muscle were studied in rabbits. The results showed that ERP of the ventricular muscle in central ischemic zone (CIZ) and border ischemic zone (BIZ) were shortened, respectively, at 10 min and 30 min after coronary occlusion (P < 0.01). The changes of ERP in TEA-treated and verapamil-treated rabbits after coronary occlusion were found to be significantly less than those in untreated rabbits. The results suggest that TEA and verapamil alleviated the degree of ERP shortening after coronary occlusion and may exhibit protective effects on the ischemic myocardium. PMID- 1293918 TI - [Protective effects of praeruptorin C and nifedipine on ischemia-reperfused injury in working rat hearts]. AB - The effects of praeruptorin C (Pra-C, 15 mg/kg, bid x 3 d, ip) on global myocardial ischemia and reperfusion were investigated in the isolated working rat hearts. The results at 35 min after reperfusion showed that as compared with the values before ischemia, AP, LVSP, +dP/dtmax, -dP/dtmax, LVEDP and T were recovered up to 80 +/- 19%, 82 +/- 16%, 78 +/- 21%, 85 +/- 11%, 136 +/- 77% and 133 +/- 21%, respectively. The corresponding parameters of Nifedipine (Nif, 60 micrograms/kg, bid x 3 d, ip) were 80 +/- 16%, 97 +/- 30%, 102 +/- 24%, 106 +/- 32%, 129 +/- 41% and 145 +/- 46%, respectively. The CF, SV and HR were recovered by 81 +/- 11%, 104 +/- 20% and 78 +/- 7% when using Pra-C and 86 +/- 11%, 106 +/- 25% and 82 +/- 11%, respectively, when using Nif. Additionally, in comparison of Pra-C and Nif with the ischemia group, the levels of creatine kinase released from cardiac cells decreased by 30% and 40%; while calcium accumulation in myocardial mitochondria were 41% and 46%, respectively. The study suggests that the protective effects of Pra-C on myocardial cells in the isolated working rat heart during myocardial ischemia are similar to those Nif. PMID- 1293919 TI - [Synthesis and bacteriostatic activity of new thiosemicarbazone derivatives- amino mercaptotriazole Schiff bases]. AB - 4-amino-3-(furan-2)-5-mercapto-1,2,4-triazole (Ia) and its ten Schiff bases derived from Ia with different aldehydes were synthesized. All the compounds were screened for activity against seven bacteria and three fungi. Most compounds were found to possess different inhibition effect on some bacteria and fungi. The azomethine group of Schiff bases is the active functional group and the substituted groups on the phenyl ring had definite effect on the bacteriostatic and fungistatic activities. 4-(5-Nitrofurfurylideneamino)-3-(furan-2)-5-mercapto 1,2,4-tria zol e (Ik) showed the most powerful antibacterial activity and broad antibacterial spectrum, while 4-salicylideneamino-3-(furan-2)-5-mercapto-1,2,4 triazole possessed strong activity against fungi. PMID- 1293920 TI - [Studies on anthraquinones from the roots of rubia cordifolia l]. AB - Seven anthraquinones were isolated from the ethyl alcohol extracts of the roots of Rubia Cordifolia L. By means of spectrometric data combined with physico chemical properties, six of them were identified as 2-methyl-1,3,6-trihydroxy 9,10-anthraquinone (I), 1-hydroxy-9,10-anthraquinone(II), 1,2,4-trihydroxy-9,10 anthrequinone(III), 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-beta-D glucoside(IV), 1,2-dijhydroxy-9,10-anthraquinone-2-O-beta-D-xylosyl(1-->6)-beta-D -glucoside(V) and 1,3-dihydroxy-2-hydroxymethyl1-9,10-anthraquinone-3-O-beta-D- xylosyl(1-->6)-beta-D-glucoside(VI). VII is a new compound. Its structure was elucidated to be 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-beta-D xylosyl(1-->2)-b eta-D- (6'-O-acetyl)glucoside. PMID- 1293921 TI - [Studies on the chemical constituents of Glycyrrhiza pallidiflora Maxim]. AB - A species of the genus Glycyrrhiza, G. pallidiflora Maxim, growing in Jiangsu and Hebei Provices of China, has been little studied before on its chemical constituents. This paper reports the isolation and chemical elucidation of five compounds from this plant, one of them is a new compound named glypallichalcone (P-2). Their chemical structures were elucidated by means of chemical and spectrometric analysis (UV, IR, MS, 1HNMR and 13CNMR) and were first reported to be present in this plant. Glypallichalcone (P-2), was found to be 4-hydroxy-2,4' dimethoxy-chalcone. The known compounds were identified to be 4'-O methylcoumestrol (P-1), N-acetyl-glutamic acid (P-3), formononetin and beta sitosterol (P-5). PMID- 1293922 TI - [New monoterpenoids from Cynanchum hancockianum]. AB - Five monoterpenoids have been isolated from the roots of Cynanchum hancockianum (Maxim) AI. Iljinski. Their structures were determined on the basis of spectral evidence. The three new compounds are: 4-p-menthane-1,7,8-triol (III), neohancoside A (IV), neohancoside B (V), and the two knowns: 4-p-menthene-1-8, 9 diol (I), and 4-p-menthane-1,8, 9-triol (II). Compound V was purified by acetylation. PMID- 1293923 TI - [Trimethylsilylation of testosterone, epi-testosterone and determination of their ratio in urine by GC-MS]. AB - The trimethylsilylation of testosterone and epitestosterone was discussed in detail in this report. Both derivative conditions under which testosterone and epi-testosterone were prepared into TMS-derivatives in the presence of mercaptoethanol as an antioxidizing agent and method for the analysis of the ratio of testosterone to epi-testosterone in urine, based on GC-MS, had been established. The conditions of detection were: carrier gas was helium, derivatives were separated with SE-54 fused silica capillary column, using temperature program and detected by using multiple ion detection mode in which the ion of m/z 432 was the monitoring ion. The method is rapid, sensitive and specific. For the ratio of testosterone to epi-testosterone (testosterone: 20 ng/microliters), there is a linearity between ratio 1:1 and 10:1 (r = 0.998), the limit of detection for testosterone and epi-testosterone is 1 ng, and the minimum concentration of detection in urine is 8 ng/ml. PMID- 1293924 TI - [Studies on the determination of plasma level and pharmacokinetic parameters of anisodamine by micellar liquid chromatography]. AB - Anisodamine is a tropane alkaloid isolated from the plant Anisodus tanguticus (Maxim) Pasch. It is an anticholine drug widely used in clinics. Micellar liquid chromatography is a new type of HPLC developed in the 1980's. Direct plasma injection technique is the application of micellar HPLC in bioanalyses. In this paper, a micellar HPLC method, which employs n-propanol as modifier, SDS as surfactant, atropine sulphate as internal standard, has been developed. By direct injection, this method was successfully applied to the measurement of plasma level of anisodamine. Application of this method to the study of anisodamine pharmacokinetics was investigated in human volunteers following a single intramuscular injection. The separation was performed in a Shim-pack CLC-CN column (150 mm x 6 mm ID, 5 microns) with a mobile phase of n-propanol-water (15:85) with 45 mmol/L SDS and total ion strength 70 mmol/L by adding phosphate, and detected at 205 nm. The standard curve was linear over the concentration range of 15-750 ng plasma level (r = 0.9972). The measurable lowest concentration was 10 ng/ml plasma (S/N = 3:1). The study of anisodamine pharmacokinetic in man was also described. PMID- 1293925 TI - [Optimization of the solvent system used for thin layer chromatography. VI. Furthering of the uniform design method]. AB - In this paper, we optimized the solvent systems of sulfa drugs and five traditional Chinese medicines for thin layer chromatography by means of uniform design method. The optimal system for the eleven sulfa drugs is benzene-n-butanol n-hexane (5.71:2.86:1.43). The optimal systems for Mu Xiang and Jiu Li Xiang are all absolute chloroform. The optimal systems for Liang Mian Zhen and San Cha Ku are all acetonitrile-ethyl ether-methyl chloride-cyclohexane (0.05:0.3:0.1:0.55). The optimal system for Jin Yin Hua is ethyl acetate-methyl chloride-formic acid (1:1:1). The method has been born out to be theoretical, simple and practical. In our opinion, it is an effective systematic method. PMID- 1293926 TI - [Studies on the analysis of stereoisomer of agarofurans by GC and GC-MS]. AB - The method for separation and identification of three pairs of agarofuran epimers (alpha-and beta-dihydroagarofuran, alpha- and beta-baimuxinol, alpha- and beta baimuxinol methyl ether) by HRGC and HRGC/MSD is described. The proportion of each pair of isomers was determined and the analytical procedure for isomers of sesquiterpenes was established. Thus, the correct synthetic route can be effectively guided and the study of agarofuran synthesis can be greatly accelerated. The method provides a reliable basis for identifying the products. MS data given in Table 2 may be useful for the identification of agarofuran derivatives. PMID- 1293927 TI - [Adsorption in stratum corneum and percutaneous penetration of propranolol hydrochloride]. AB - The sorption and rate of permeation of propranolol hydrochloride were measured as a function of drug concentration in the solution bathing rat skin in vitro. The sorption isotherm was nonlinear, and can be expressed in Langmuir form. The lag time and apparent permeability coefficient through intact skin decreased as the concentration of donor compartment increased, and those through stripped skin were not varied. These results indicate that an adsorption process existed when propranolol hydrochloride penetrated through the stratum corneum. Based on the adsorption--diffusion theory, a mathematical formula was developed for expressing the relationship between the concentration of drug and permeability coefficient through the skin quantitatively. PMID- 1293928 TI - [Hypotensive effects of safflower yellow in spontaneously hypertensive rats and influence on plasma renin activity and angiotensin II level]. AB - Safflower yellow (SY) is a mixture of chalconoid compounds extracted from Carthamus tinctorius L. Ig SY 1-2 g.kg-1.d-1 lowered the blood pressure of spontaneously hypertensive rats (SHR), for about 1.86-3.86 kPa. Five weeks after administration of SY, the plasma renin activity and angiotensin II level diminished in the SHR experimental groups. These suggest that the decrease of blood pressure is mediated by the renin-angiotensin system. PMID- 1293929 TI - [A new alkaloid from Menispermum dauricum DC--N-desmethyldauricine]. AB - A new phenolic dauricine-type alkaloid together with the know dauricine were isolated from the rhizoma of Menispermum dauricum DC cultivated in Xianning district, Hubei province. Dauricine was obtained as the major alkaloid and was confirmed by comparison with authentic sample. The new alkaloid is an unstable white powder: Based on spectrometric analysis (UV, IR, FAB-MS and 1HNMR) and N methylation which offered dauricine dimethiodide (V), the structure was elucidated as RR, N-desmethyldauricine (II), which was isolated for the first time from nature. PMID- 1293930 TI - [Studies on the chemical components of Viscum coloratum. VIII. Isolation and structure of 3-beta-D-glucopyranosyloxy-butanol-2]. AB - From the ethanol extract of Viscum coloratum (Kom.) Nakai, a glucoside of aliphatic diol and three other glucosides were isolated. Based on chemical and spectroscopic analysis, the structures have been elucidated as 2-beta-D-glucosyl 3-methylpropanol (VIII), syringin (IX), eleatheroside E (X) and syringenin-4'-O-D apiosylglucoside (XI). VIII is a new glucoside of aliphatic diol and named 3-beta D-glucopyranosyloxy-butanol-2. Three other compounds (IX-XI) were found for the first time in this plant. PMID- 1293931 TI - [Separation and identification of impurities in mifepristone]. AB - In this paper we presented details of methods for the TLC and HPLC separation of mifepristone and its impurities. The results showed that Chinese mifepristone contained five impurities. The major one was isolated by sillca gel column chromatography and thin layer chromatography. On basis of its UV, IR, EIMS and 1HNMR spectral analysis and by comparison with reference substance, it was identified as (11 beta, 17 beta)-11-[(4-methylamino)phenyl]-17-hydroxy-17-(1 propyny)-estra-4 ,9-dien-3 - one. Meanwhile, TLC analysis indicated that French mifepristone contained the same impurity. PMID- 1293932 TI - [Effect of panaxatriol saponins isolated from Panax notoginseng (PTS) on myocardial ischemic arrhythmia in mice and rats]. AB - PTS, one of the major effective components of Panax notoginseng was found to exert remarked antiarrhythmic activities on coronary artery ligation induced ischemic and reperfused arrhythmias in rats. PTS also reduced the size of myocardial infarct. For i.v. CaCl2-Ach induced atrial fibrillation and/or flutter in mice, PTS produced a significant protective effect. In addition, PTS showed an action of prolonging the life under the condition of normobaric hypoxia. PMID- 1293933 TI - [Effect of ageing on hepatic biotransformation function and microsomal membrane fluidity in rats]. AB - Microsomes were isolated from livers of male Sprague-Dawley rats at 3-4, 14 and 24 months of age for each group for the determination of monooxygenase components and drug metabolism activities. Some GSH-related enzyme activities in microsomes and cytosol were also measured. DPH (1,6-diphenyl-1,3,5-hexatriene) was used to determine the microsomal membrane lipid region fluidity. Microsomal cytochrome P 450 content and NADPH-cytochrome c reductase activities remained unchanged in old rats, but there were significantly decreases in cytochrome P-450 dependent aminopyrine N-demethylase and aniline hydroxylase activities. Glutathione S transferase (GST) in cytosol and microsomes and glutathione peroxidase (GSH-Px) in cytosol were also decreased in old rats. Simultaneously, microsomal membrane fluidity of 24-month old rats decreased (measured at 25 degrees C and 37 degrees C), accompanied by an elevation of cholesterol/phospholipid ratio. Results suggest that there might be some relationship between the lipid environment and membrane fluidity changes and the decreases of hepatic biotransformation function. PMID- 1293934 TI - [Effects of platelet activating factor on the cerebrovascular permeability in rats and the protection by drug]. AB - The action of platelet activating factor in the rat brain was detected by Evans blue staining after injection of PAF into the rat brain. The results show that PAF increased the Evans blue staining of the brain, but no staining was observed without prior injection of PAF. Meanwhile, PAF was shown to stimulate the release of 14C-arachidonic acid (14C-AA) in the cerebral microvascular smooth muscle cells (CMSMC). SZ-1, a new synthetic drug, dose-dependently inhibited the Evans blue staining of the rat brain and the PAF induced 14C-AA release in CMSMC. These results indicate that the action of PAF in the rat brain might be related to the stimulation of AA release. SZ-1 may antagonize the PAF receptor and protect the brain from PAF induced damage. PMID- 1293935 TI - [Synthesis and antitumor activity of 4-alkylthio-4-deoxy-4' demethylepipodophyllotxin derivatives]. AB - As a continuing part of our study on the chemistry and antitumor activity of podophyllotoxin, 11 new C-4 S-substituted podophyllotoxin derivatives were synthesised and screened in vitro against L1210 leukemia and KB cells. Thus, 4' demethylepipodophyllotoxin was reacted with thiols in the presence of BF3. Et2O or trifluroacetic acid to give thioethers. In addition, 4-bromo-4-deoxy-4' demethylepipodophyllotoxin, when reacted with thiols, also gave rise to corresponding thioether (4-alkylthio-4-deoxy-4'-demethylepipodophyllotoxins). Compounds 10 and 12 have the same activity as etoposide in the inhibition against L1210 leukemia, and compounds 9, 10, 12 and 15 also have comparable activity with etoposide against KB cells. PMID- 1293936 TI - [Synthesis and radiosensitizing activity of benzimidazoles]. AB - In search for effective radiosensitizer with low neurotoxicity, benzimidazole compounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl alpha-(2-nitrobenzimidazolyl-1)-formate(1) or ethyl alpha-(2-hydroxybenzimidazolyl-1)-formate(2), depending upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,2-epoxy-3-chloropropane gave a cyclized compound which was confirmed to be benzimidazo(1,2b)-5'-chloromethyl oxazolidine(3). In attempt to increase hydrophilicity, 1-substituted 2(3' pyridyl)-5-nitrobenzimidazoles were prepared by reaction of 2-(3'-pyridyl)-5(6) nitrobenzimidazole(4) with alkyl epoxides or ethyl chloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich ascites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizing activity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be 1.50, 1.52 and 1.65 respectively. PMID- 1293937 TI - [Studies on the cyclopeptides of Stellaria dichotoma L. var. Lanceolata Bge]. PMID- 1293938 TI - [Studies on the alkaloid constituents of Jiangyou fu-zi Aconitum carmichaeli from Sichuan]. AB - Six compounds were isolated from the aqueous extract of Aconitum carmichaeli Debx (cultivated in Jiang-you region of Sichuan province). Five of them have been identified as uracil (I), songorine HCl(II), karakoline(III), neoline(IV), and fuzitine(VI). Compound V is a new C19-diterpenoid alkaloid determined as C33H47NO9 and named neojiangyouaconitine. PMID- 1293939 TI - [Studies on chemical constituents of the gall of Python molurus bivittatus Schlegel]. AB - Two constituents were isolated from the gall of Python molurus bivittus Schlegel, one is sodium taurodeoxycholate (I). The other is a new compound--sodium tauropythocholate (II). Its structure was elucidated as 3 alpha, 12 alpha, 16 alpha-trihydroxy-5-cholan-24-oic acid N-[2-sulfoethyl] amide by IR, 1HNMR, 13CNMR, MS 13C-1H COSY, and chemical reaction. PMID- 1293940 TI - [Studies on the chemical constituents from the skin of Bufo bufo gargarizans Cantor]. AB - Four bufotoxins were isolated by means of preparative reversed phase HPLC from the water soluble fraction of the skin of Bufo bufo gargarizans Cantor. On the basis of their spectral data (UV, IR, 1HNMR, 13CNMR, EIMS and FDMS), amino acid analyses and chemical properties, they were identified as bufotalin 3 succinoylarginine ester(I), bufalin 3-succinoylarginine ester(II), cinobufagin 3 succinoylarginine ester(III), and resibufogenin 3-succinoylarginine ester(IV). Compound I is a new bufotoxin. PMID- 1293941 TI - [The effect of molecular volume and partition coefficient on percutaneous absorption]. AB - A series of 8 p-aminobenzoate esters were selected as model drugs to study the effect of molecular volume and partition coefficient on percutaneous absorption. The octanol/water partition coefficient and solubility of these compounds were determined and their penetration rate through rat skin in vitro was measured using a Keshany-Chien diffusion cell. The results showed that when the molecular volume was increased the permeation coefficient was decreased. However, when the partition coefficient was increased, the permeation coefficient was increased at first and then reached a plateau. The mathematical formula has been derived from a bi-layer diffusion model to show how the molecular volume and the partition coefficient influence the permeation coefficient. The formula could be used to estimate the permeation coefficient of drug through skin. PMID- 1293942 TI - [Determination of oleanolic acid in Achyranthes bidentata BLume and its preparations by supercritical fluid chromatography]. AB - Capillary SFC was used for the determination of oleanolic acid in Achyranthes bidentata BLume and its preparations Tianmawan, Jinguishenqiwan and Hechedazaowan. The amount of oleanolic acid in the root of Achyranthes bidentata BLume was 1.75-2.19% (mean +/- SD = 1.94 +/- 0.17%). The limit of detection was 9.605 x 10(-11) g. The method is highly sensitive, accurate, reproducible, simple, rapid and specific, so, it can be extensively used for the determination of other preparations and crude herbs. PMID- 1293943 TI - [On the correction of systematic errors of analytical methods used in the content uniformity test]. AB - In this paper, the constant and proportional systematic errors of analytical methods for the content uniformity test were studied with reference to the accurate analytical method for the assay. Seven monographs of tablets admitted to USP(XXII), Ch P (1985, 1990) and JP(XI) were taken as cases in point and the systematic errors of two of them, i.e. digoxin and nitroglycerin tablets, were ascertained by the test of significance. To improve the accuracy of analytical methods for the content uniformity test, a correction formula more reasonable and convincing than that of USP (XXI, XXII) was proposed, and its theoretical basis described briefly. PMID- 1293944 TI - [Zero-crossing derivative spectrophotometry for the determination of three components in paracetamol compound tablets]. AB - The zero-order derivative absorption spectra of aspirin, paracetamol and caffeine are closely overlapping. In this paper, a zero-crossing derivative spectrophotometry combined with simultaneous equations is proposed for the determination of the three components in a mixture without the need of prior separation. Satisfactory results were obtained. The method is reproducible, accurate and rapid. Calculation is not complicated. This method could be applied to biological fluid analysis. PMID- 1293945 TI - [A study on the decomposition kinetics of vitamin C tablet]. AB - Under the condition of relative humidity less than the critical relative humidity, the discoloration rate and decomposition rate of vitamin C tablet and the discoloration rate of vitamin C tablet in solution were studied at temperatures 60-90 degrees C and relative humidities 60%-80%. The general equation of the relationship between the apparent rate constant k, absolute temperature T and relative humidity RH is: k = k' exp(-E/RT) exp(mRH), where k' and m are constants, E is apparent activation energy. The values of k', m and E for discoloration, decomposition and discoloration in solution are different. PMID- 1293946 TI - [Study of the relationship between structure and anticonvulsant activities of 5 substituted-1-butry-3-pyrazolidinones and their synthesis]. AB - According to the quantitative structure-activity relationship studies of 3 pyrazolidinones with different substituent on positions 1 and 5 reported previously, the anticonvulsant activity is parabolically related with the total fragment constent (Fr hydrophobic parameter) of the 1 and 5 substituents of 3 pyrazolidion. The optimum Fr was about 5.6. Therefore, eleven new 5-substituted-3 pyrazolidinones have been synthesized. Pharmacological test showed that they are all potent anticonvulsant agents. Among them 1-n-butyl-5-(p-chlorophenyl)-3 pyrazolidinone was shown to be the most potent so far synthesized. PMID- 1293947 TI - [Synthesis of N-(4-substituted amino-4-oxobutyryl)-N-substituted glycines]. AB - Nine N-(4-substituted amino-4-oxobutyryl)-N-substituted glycines expected to have inhibitory activity on angiotensin-converting enzyme were synthesized. All of the title compounds and their t-butyl esters were unreported in the literature. In preliminary test in rats, compounds V2, V6 and V7 showed marked hypotensive activity. PMID- 1293948 TI - [Behcet's disease. Experience of an internal medicine service from 1982 to 1991]. AB - The authors present the results of a retrospective study on Behcet's disease, concerning 19 patients observed in Medicine Service 2 (Santo Antonio dos Capuchos Hospital) between 1982 and 1991. There were 15 male and 4 female patients, with a mean age of 33. The clinical manifestations were: oral--100%, ocular--100%, genital--89%, articular--79%, cutaneous--68%, general non-specific manifestations -52%, venous--26%, peripheral nervous system--21%, central nervous system--10% and persistent headaches--10%. PMID- 1293949 TI - [Psychiatric morbidity in general hospital inpatients]. AB - Psychiatric morbidity was studied in 73 patients of three Units (Medicine, Surgery and Obstetrics) of a general hospital (S. Francisco Xavier Hospital, Lisbon). In the first stage, the patients were clinically evaluated by their doctors. In the second stage, psychiatrists using the General Health Questionnaire (G.H.Q. 30) interviewed all the patients according to the clinical evaluation, 41% of the patients had a significant psychological disorder. However, very significant differences were found between the prevalence rates in the three units. As defined by the G.H.Q. 30, 50 patients (68.5%) had psychiatric disorders, which is statistically different from the results obtained through clinical evaluation. The depression and anxiety syndromes were the most frequent disorders. Organic mental disorders were less frequent and almost limited to medical patients. The results of this study confirm a high rate of psychiatric morbidity in the general hospital, although considerable differences exist between the three units included in the study. We can also conclude that many psychiatric disorders are not correctly identified. This fact, more frequent in units where there is a more brief doctor-patient relationship, supports the necessity of implementing liaison psychiatry programs. PMID- 1293950 TI - [Depression as the sign of true self]. AB - Referring to examples from the poetry of Fernando Pessoa and Mario de Sa Carneiro, we draw attention to the narcissistic relationship between mother and baby, to the role of the mirror-image of the mother's face, and to the organization of a false self caused by a deficiency both of that function, and of the narcissistic investment of the child. The false self is a defence mechanism which protects the true self. This may appear as a depressive state with a feeling of loss and emptiness. The depression is, in such cases, a sign and a clue which may lead to the revelation of the true self. PMID- 1293951 TI - [Blood transfusion in sickle cell disease]. AB - Sickle cell disease is a genetic disorder characterized by the presence of hemoglobin S. This hemoglobin has a low affinity for oxygen, allowing a good oxygenation of tissues with low levels of hemoglobin. Therefore, blood transfusions are not necessary to correct basal anemia, but are indispensable in the treatment and prevention of some complications. Detailed indications for blood transfusions are presented, as well as the different types of transfusion usually performed: simple, exchange and hypertransfusion. Finally, reference is made to the preferable blood components to be used, complications related with transfusion, the preventive measures to be taken and the need for a patient's transfusion record. PMID- 1293952 TI - [Safety in hemophilia A treatment. Viral inactivation of FVIII:C concentrates]. AB - In the last thirty years, factor VIII concentrates have been the mainstay of hemophilia treatment, first as wet cryoprecipitate and later as dry concentrates commercially available. The evidence of a high risk of blood-born virus transmission by these products provoked the development of new methods for virus inactivation. We report these methods with special attention to their safety, and mention the new perspectives of treatment with recombinant DNA FVIII:C and ultimately by gene insertion therapy. PMID- 1293953 TI - [Evaluation of blood esterases in Alzheimer's disease]. AB - The aim of this work was to evaluate a possible correlation between erythrocyte acetylcholinesterase activity (AChE) and membrane fluidity expressed by fluorescence polarization of--1,6--diphenyl 1,3,5--hexatriene (DPH). Blood samples of 34 Alzheimer's patients (18F and 16M) were obtained and haemoglobin concentration, haematocrit, plasma (butyrylcholinesterase, BuChE) and erythrocyte (AChE) esterase activities and fluorescence polarization after introduction of DPH in erythrocyte membrane have been determined. Results were compared with values obtained from blood samples of 34 apparently healthy volunteers with the same age variation (53-82 years). There was no correlation between AChE activity and fluorescence polarization in the control group nor in the patients' group. There was a significant negative correlation (r = -0.82; p < 0.001) between mean corpuscular hemoglobin concentration (MCHG) and erythrocyte acetylcholinesterase activity in Alzheimer's patients. This correlation suggests that any variation of internal globular viscosity (or MCHG) may indirectly affect AChE enzymatic activity and consequently contribute to the loss of interrelation between AChE activity and membrane lipid fluidity, verified in the present work. A biological marker for Alzheimer's disease diagnosis remains to be discovered. PMID- 1293955 TI - [Research in child mental health]. AB - Some considerations are made about current child psychiatry research and its future challenge. We analyse some studies about parental psychopathological influence in the early relationship, mentioning obstacles and advantages of some clinical and epidemiological research methods. We emphasize the value of interaction, observation and the use of videoscopy in infant clinical research. In Portugal, the lack of motivation to work in mental health research is an impediment to establishing clinical and training priorities. PMID- 1293954 TI - [Drug surveillance: concepts, objectives, and methods]. AB - Adverse reactions to drugs, by their frequency and morbidity, constitute a very important problem in clinical practice today. However, it is not always possible to establish the definitive causal relationship between the drug and the clinico laboratory situation. This is not only due to the variability of these findings and the inherent difficulties of the methodology used, but also the fact that most doctors show little sensitivity to such an important subject. In this paper we present a short review of the drug surveillance programme: basic concepts, objectives and the most important methodology, as well as the current situation in the EEC countries. PMID- 1293956 TI - [Ethics, health & society]. AB - The sudden advent of new technological devices and sophisticated methods in both biological research and medical practice alerted different social groups to the development of unprecedented problems for moral counsel and decision-making. The field of study called bioethics grew out of religiously motivated concerns, but nowadays it attracts the attention of politicians, lawyers, religious thinkers, philosophers, scientists and doctors. Bioethics is becoming a sphere of interest to an increasing number of people. Each of these groups bring their own values, which are sometimes not in total agreement with the traditional values of medical ethics, to discussion. Therefore, the Author defends a more active participation of doctors through their representative bodies in the discussion of policies concerning the research and development of new technologies, and also the individual use of them when they are available, so that the practice of medicine may preserve the hippocratic legacy, accepting only the external influences when they are not in conflict with the intrinsic morality of medicine. PMID- 1293957 TI - [Beyond appearances... (neuropsychiatric symptoms as presentation form of insulinoma)]. PMID- 1293958 TI - [Myxedema coma]. AB - Five patients, 4 female and 1 male, aged 45 to 73, were observed in myxedema coma between 1984 and 1992. In three patients hypothyroidism was not known. Depressed consciousness, hypothermia, bradycardia and no goiter were common to all and a precipitating factor could be identified in 3 of them. Therapy included L thyroxine and/or triiodothyronine by nasogastric tube, hydrocortisone and supportive measures. Outcome was good in the 2 patients with known precipitating event, less impaired consciousness and normalization of body temperature by the third day of treatment. PMID- 1293959 TI - Hippocampal rhythmic slow activity (RSA) in the cat after intraseptal injections of muscarinic cholinolytics. AB - Influence of intraseptal injections of cholinolytics on hippocampal rhythmic slow activity (RSA) was investigated in cats. Results of the first experiment have shown that neither atropine (At) nor scopolamine (Sc) injected into the medial septum in doses of 20 micrograms prevented the induction of RSA by a cholinergic (carbachol-CCh) stimulation of the anterior hypothalamus as well as by electrical stimulation of posterior hypothalamus or periaqueductal grey substance (PAG), and were only partially effective in prevention of the spontaneous RSA. RSA did not appear spontaneously and could not be induced by electrical brain stimulation after intraperitoneal injections of At (2.0 mg/kg) or Sc (0.2 mg/kg). Results of the second experiment have shown that intraseptal injections of At (5.0 or 10.0 micrograms) are also ineffective in prevention of RSA induction by CCh (2.5 micrograms) injected into the same septal locus. The data suggest that the medial septum cannot be regarded as the common muscarinic link within the RSA generating system of the cat. PMID- 1293961 TI - The differences between simultaneously or separately tested instrumental sexual responses in rats. AB - The instrumental sexual responses were investigated in male and female rats in the following experimental situations: (1) when the instrumental responses were tested simultaneously in the male and the female (2) when the male was a subject and the female was used as a reward only, and (3) when the opposite was true. The analysis of the data indicated that if the instrumental responses were tested separately in male and female rats, the male response latencies were significantly shorter than the female ones, while during the simultaneous testing no such difference was observed. This phenomenon seems to be a result of avoiding by the male rat of the frustration which occurs during waiting for the female after accomplishing the instrumental response. PMID- 1293960 TI - Pharmacological and physicochemical properties of collagen breakdown-products. AB - It has been found that the pharmacologically active, low molecular products obtained by digestion of telopeptides-deprived type I collagen with bacterial collagenase is a heterogenous mixture of at least 21 peptides of different molecular weight. They contain 3 to 15 amino acid residues. About 80% of them are tripeptides of the sequence Gly-Pro-X. The most abundant are two peptides: Gly Pro-Hyp and Gly-Pro-Ala. The peptides injected into the lateral cerebral ventricle of the rat evoked some behavioral effects. They decreased the psychomotoric activity (evaluated with Lat's test) and increased the cataleptic action of haloperidol. On the other hand, they did not exert any effect on amphetamine-induced stereotypy and did not counteract the apomorphine-induced stereotypy. PMID- 1293962 TI - Asymmetry in visual evoked potentials to gratings registered in the two hemispheres of the human brain. AB - The study aimed at testing, by a visual evoked potential method, the hypothesis of the hemispheric specialization in processing of high and low-spatial frequencies. Twenty four right-handed subjects (12 males and 12 females) were presented with square-wave vertical gratings of various spatial frequencies (0.67, 0.86, 1.20, 2.00, 2.40, 3.00, 3.30, 6.00 and 7.50 c/deg). Gratings were presented in nine separate blocks each containing 64 exposures. Time of exposure was 30 ms and the interstimulus interval varied from 2 to 3.5 s. VEPs were recorded with electrodes located at O1 and O2 and referred to Cz according to the 10/20 system. Amplitudes and latencies of two VEPs components (N130-150 and P200 240) were analyzed. The results showed larger amplitudes of VEPs registered in the right hemisphere of both males and females. This difference, however, was apparent in the earlier component of VEPs in females and in the later component in males. The observed hemispheric asymmetry did not depend on the spatial frequency of grating. Females demonstrated longer latencies than males for both N and P components. Our data suggest that the right hemisphere predominates in processing grating stimuli, but the dynamics of this process differ in the two sexes. The results do not support Sergent's hypothesis which postulate the right hemisphere specialization for low spatial frequencies and the left hemisphere specialization for high spatial frequencies. PMID- 1293963 TI - Hemispheric asymmetry in event related potentials associated with positive and negative emotions. AB - Event-related potentials from symmetrical points of the left and right frontal and occipital cortex were recorded while subjects experienced positive and negative emotions. The emotions were elicited by either missing or hitting a target with a photoelectric gun. Twenty three right-handers (10 males and 13 females) were tested. Each subject took part in two sessions. In the first session the subjects were informed about their performance (hit or miss) after each shot. In the second, control session, no feedback was given. The amplitudes of P180 potential registered from the occipital cortex were higher in the right than in the left cerebral hemisphere, irrespectively of subjects' performance (i.e. a miss or a hit). No such tendency was observed in potentials registered from the frontal cortex. These regularities emerged only in the feedback situation, i.e. when subjects were informed about their performance, although higher ERPs were registered for hits than for misses. The results support the hypothesis that the posterior region of the right hemisphere is more engaged than the left one in experiencing emotions, irrespectively of their sign. PMID- 1293964 TI - Response strategy in two-choice visual discrimination in the rabbit. AB - Rabbits were trained to discriminate striated patterns of different orientation in a two-choice discrimination box. After the 90% correct level had been reached, motor behaviour was studied during visual discrimination. It was found that the animals made their decision after seeing one of the two stimuli. This finding is in disagreement with an earlier study from which it was concluded that the animal's choice is mainly controlled by the unrewarded stimulus (Van Hof and Van Hof-van Duin 1984). PMID- 1293965 TI - The role of calcium in the regulation of melatonin biosynthesis in the retina. AB - Vertebrate retina rhythmically produces melatonin, a hormone involved in the regulation of several intraocular processes cued by environmental lighting conditions. Calcium ions play an important role in the induction process of serotonin N-acetyltransferase (NAT), a key regulatory enzyme in melatonin biosynthetic pathway. The physiological, i.e. nocturnal, increase of NAT activity in the retina depends on transmembrane transport of Ca2+ through the L-type of voltage-sensitive calcium channels. It is suggested that Ca2+ may regulate NAT activity indirectly, by affecting the intracellular cyclic AMP content, which is, in turn, critical in the regulation of melatonin biosynthesis. The mode and mechanisms of Ca2+ action on processes governing melatonin formation in the retina are discussed. PMID- 1293966 TI - Interaction between phosphatidylserine biosynthesis and protein kinase C activation in neuroblastoma NB2a cells. PMID- 1293967 TI - Special issue dedicated to Professor Giuseppe Andrea Buscaino. PMID- 1293968 TI - [Dopaminergic neurons and clinical neuropsychiatry]. AB - The neurobiologic acquisitions in the realm of the dopaminergic neurons are analyzed and discussed in connection with related clinical problems. Both "neurological" (extrapyramidal; autonomic; neuro endocrine) and "psychiatric" (bradifrenia; dissociation; depression of mood) symptoms and syndromes--whose pathophysiology and pharmacotherapy involves dopaminergic transmission--are discussed. The peculiar physiological meaning of dopaminergic neurons between the monoaminergic adaptive systems is stressed. PMID- 1293969 TI - Luigi Rolando and anatomy of the nervous system at the dawn of the 19th century. PMID- 1293970 TI - Headache and migraine in the scientific traditions of the Salerno Medical School. PMID- 1293971 TI - The use of EEG activating procedures in epileptology. AB - Epileptic seizures and EEG interictal paroxysmal activity (PA) usually occur in an apparently unpredictable fashion, and a small number of patients with truly epileptic seizures may not present any PA on repeated EEGs. With the aim of increasing the possibility of recording interictal or ictal PA, several activation procedures are routinely carried out. In rarer instances, seizures seem to be more or less specifically evoked by unusual triggering procedures, or are chronologically related to biological rhythms. These different activating procedures may have different effectiveness depending on the type of epileptic syndrome. In the present paper the Authors describe the different activating procedures, both routinely employed and unusual ones. Their possible differential use with regard to the different epileptic syndromes and to the specific epileptologic history of the patient are examined. A selective use of these procedures is suggested, as an accurate choice of such techniques may increase the diagnostic usefulness of the EEG, in particular in patients whose basal recording is not contributory. PMID- 1293972 TI - Photoparoxysmal response on eye closure in photosensitive patients. AB - The Authors studied the presence of photoparoxysmal response (PPR) during intermittent photic stimulation (IPS) in 2,888 consecutive EEG recordings. PPR was present in 2.3% of EEGs and 10% of all patients referred to EEG laboratory for epilepsy (45 patients, 18 males, 27 females (M:F ratio 1:1.5), mean age 12 yrs). In 24 (53.3%) of these patients PPR was evident only (24.4%) or strikingly (28.9%) on eye closure during IPS. In 7 patients no other epileptic abnormalities were found on basal EEG and during hyperventilation, nor during IPS with eyes closed and with eyes open. The Authors consider the eye closure during IPS the most useful method to reveal a PPR in photosensitive patients and believe that a good IPS technique must include this procedure in the routine EEG examination. PMID- 1293973 TI - "Memory-scanning" event-related potentials. Correlations with verbal and performance scores. AB - Auditory and visual event-related potentials (ERPs) to a digit probe identification task in a modified Sternberg paradigm have been compared with psychological tests of verbal and performance ability (WAIS) in 19 healthy subjects. We have found a significant correlation between ERP amplitude and test scores. The higher the scores the "more negative" the responses. Correlations were stimulus-modality dependent. Auditory and visual ERPs were strongly correlated with "verbal" and "performance" IQ, respectively. The characteristics of these IQ-dependent electrophysiological features suggest that they may be related to the ability to allocate attention. PMID- 1293974 TI - In vivo administration of propranolol decreases exaggerated amounts of serum TNF alpha in patients with migraine without aura. Possible mechanism of action. AB - Patients with migraine without aura (MWA) display elevated amounts of Tumor Necrosis Factor (TNF)-alpha in their sera. In this study in 18 patients with MWA the in vivo effect of propranolol, a beta blocker agent, was evaluated with regard to the TNF serum levels before and after treatment. Results show that in 9 out 11 patients exaggerated serum concentrations of TNF reverted to normality after three months of therapy. Some hypotheses on the mechanisms of action of propranolol in terms of modulation of the immune response are formulated. PMID- 1293975 TI - Acute effect of flunarizine on saccadic eye movements. AB - It has been postulated that flunarizine (FNZ) acts on the brain through a stabilizing effect on membrane electrical activity of neurones. It has been also suggested that neurogenic events characterized by an increased tendency of nerve cells to fire, could be involved in the pathogenesis of migraine and epilepsy. The study was aimed to assess the effect of a single oral dose of FNZ (20 mg) on CNS specific functions by means of computer analysis of saccadic eye movements. The study was performed on six healthy volunteers according to a double-blind, cross-over, placebo controlled design. FNZ produced a significant reduction only of peak saccadic velocity, thus suggesting a rather specific and selective effect on the burst cells of the para-median pontine reticular formation. PMID- 1293976 TI - Cytokines in the pathogenesis of multiple sclerosis. AB - The authors evaluate the involvement of various cytokines (interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha and gamma-interferon) in the pathogenesis of multiple sclerosis. The cytokines might participate in nervous tissue damage by promoting demyelination and oligodendrocyte injury or by enhancing local immune response. In addition, several authors reported increased levels of some cytokines in serum and cerebrospinal fluid of patients with multiple sclerosis. These findings suggest that cytokines can play a significant role in the immunopathogenesis of the disease. PMID- 1293977 TI - The role of cytokines in AIDS-dementia complex. PMID- 1293978 TI - [Clinical and electrophysiological findings in various hereditary sensory neuropathies]. AB - An electrophysiological study, comprehensive of peripheral sensory and motor conduction velocity (SCV, MCV), motor cortical stimulation (CS), median nerve somatosensory evoked potentials (SSEPs), brainstem evoked potentials (BAEPs) and sural nerve biopsy, was performed on 100 hereditary ataxia patients: 48 with Friedreich's ataxia (FA), 18 with Early Onset Cerebellar Ataxia (EOCA) and 34 with Autosomal Dominant Cerebellar Ataxia (ADCA). An early "peripheral" and "central" sensory impairment was observed in FA probably due to axonal loss and not related to disease severity or duration. On the contrary, BAEP and CS findings suggested a progressive involvement of the auditory and motor pathways. The presence of a non progressive sensory neuropathy allowed a distinction of EOCA patients in two groups: with and without peripheral neuropathy. The clinical and genetic heterogeneity was confirmed by the variability of evoked potential results. The ADCA patients showed the mildest degree of electrophysiologic abnormalities with an involvement of the peripheral pathways, both sensory and motor, more frequent than the central ones. PMID- 1293979 TI - Evoked potentials in brain death. A critical review. AB - The development of transplant surgery has determined the necessity to revise criteria and to apply new electrophysiologic techniques to add further informations when survival of brain function is in question. The EPs, which provide a sensitive tool for assessment of integrity of main sensorial systems, could have a place in the electrophysiologic evaluation of the brain death. This review deals with the role of EPs in brain death and points out the main patterns found in that clinical condition. PMID- 1293980 TI - Plasma exchange and i.v.-immunoglobulins: new approaches to the treatment of Guillain-Barre' syndrome. AB - We report the results obtained with plasma exchange (PE) in 26 patients (18 males, 8 females) with Guillain-Barre Syndrome (GBS) of maximal severity and also the results with IVGG in 7 patients (3 males, 4 females) where PE could not be employed. A complete clinical and neurophysiological evaluation was carried out. A follow-up was effected at regular intervals for a year. From this study the efficacy of PE in GBS was confirmed and a correlation was found between the amplitude of the muscular potential registered in the acute phase and the prognosis of the illness. PE is not effective for patients with a fulminant course and blocking of conduction. Good results have been obtained with IVGG therapy, which seems to be safe and effective whenever PE is not possible. PMID- 1293982 TI - [Magnetic resonance angiography in occlusive/stenotic pathology of the intra and extracranial cerebral vessels]. PMID- 1293981 TI - Antiphospholipid antibodies in young adults with cerebrovascular ischemic disease. AB - In this survey we reviewed some of the most recent laboratory and clinical studies on cerebral ischemia in young patients with antiphospholipid antibodies (aPLs). A strong association between aPLs and cerebrovascular ischemic disease has been documented, but the underlying pathogenetic mechanism remains unclear. Furthermore, long-term prognosis is not clear since too few controlled longitudinal studies had been reported. Further prospective clinical trials are needed to define risk factors, to identify different subgroups of patients, and to lead to an effective therapy. PMID- 1293983 TI - Congenital fiber type disproportion in two sisters. A clinical and histopathological study. AB - Two sisters aged 27 and 29, respectively, born of nonconsanguineous parents, presented diffuse malformations at birth, followed by psychomotor retardation, reduction in muscle strength and easy fatigability at limbs. The clinical and neurophysiological examination as well as the histochemical study were indicative of a myopathic condition. Fiber type analysis in both patients showed that the type I fiber mean diameter was smaller than that of type II fibers by 12%. Clinical and laboratory findings are consistent with those observed in most cases of Congenital Fiber Type Disproportion, as described in literature. PMID- 1293984 TI - Classifications of hereditary ataxias. A critical overview. AB - The classifications of hereditary ataxias (HA) proposed from 1907 to 1984 are reviewed. An analysis is provided of the possible variables in the classification of HA, including inheritance, known metabolic or other cause, localization of pathological lesions, clinical signs, natural history, epidemiology, diagnostic tools. Harding's classification is assumed to be the best clinical tool to support molecular genetics studies. However, we suggest the inclusion of Late Onset Recessive Cerebellar Ataxias in Harding's classification. Some exceptions must be considered for the diagnostic criteria of Friedreich's disease. Early Onset Cerebellar Ataxia with retained tendon reflexes (EOCA) is probably a heterogeneous entity. PMID- 1293985 TI - Early onset hereditary ataxias of unknown etiology. Review of a personal series. AB - Among 300 patients affected by hereditary ataxia, 94 received the diagnosis of Friedreich's disease, 12 of Late Onset Friedreich's disease, 27 of Early Onset Cerebellar Ataxia with retained tendon reflexes, 10 of Progressive Myoclonic Ataxia, 4 of Ataxia with hypogonadism and 2 of Ataxia with hearing loss. Only Friedreich's disease appears clinically homogeneous, whereas the others are not specific entities and each of them probably includes different diseases. PMID- 1293986 TI - [Clinical, multimodal electrophysiological study of a family with progressive cerebellar ataxia and late deafness and an autosomal recessive inheritance]. AB - We described the clinical, electrophysiological (electromyography, sensory and motor nerve conduction study, somatosensory evoked potentials, brainstem auditory evoked potentials, visual evoked potentials) and neuroradiological (brain magnetic resonance) data in 3 siblings (2 males and 1 female, age range: 54-48 years) affected by autosomal recessive late onset cerebellar ataxia. The 3 patients showed at the electrophysiological examination: mild peripheral neuropathy, involvement of somatosensory pathways both on central and peripheral side. A mild cerebellar atrophy, most evident in the female more severely disabled, was found by magnetic resonance. PMID- 1293987 TI - [Eye movement disorders in hereditary degenerative ataxia. Electro-oculographic study of 11 cases]. AB - An electro-oculographic study has been performed in 11 patients affected by hereditary degenerative ataxias (5 Friedreich's ataxias, 4 olivopontocerebellar atrophies and 2 late onset cerebellar ataxias). Electrooculographic records were obtained during saccades, pursuit movements and fixed gaze. Saccadic latency, saccadic speed and morphologic features were studied. In Friedreich's ataxia ocular motility was less accurate than in olivopontocerebellar atrophy and in late onset cerebellar ataxia. PMID- 1293988 TI - Dopa responsive dystonia and juvenile Parkinson's disease: two subtypes of the same disorder? AB - We report a sporadic case of Dopa responsive dystonia and two families with different combinations of parkinsonism and dystonia. The possible relationships between Dopa responsive dystonia and early onset Parkinson's disease are discussed. PMID- 1293989 TI - Progressive myoclonus epilepsies. Criteria for diagnosis on the basis of the follow-up of 37 cases. AB - The authors report the clinical criteria for the diagnosis of progressive myoclonus epilepsies on the basis of their experience following 34 cases (2 with sialidosis, 2 with MERRF, 4 with Lafora disease, 24 with Unverricht-Lundborg type, 4 with ataxic myoclonus). 3 rare forms of PME are also reported: a case of lipoma and PME, a family with dentato-rubro-pallido-luysian atrophy and a family of myoclonus epilepsy, Hartung type. The autonomy of Ramsay Hunt syndrome is discussed on the light of recent molecular genetic data. PMID- 1293990 TI - Progressive rubella panencephalitis. Follow-up EEG study of a case. AB - Progressive rubella panencephalitis is a very rare slow virus disease of the nervous system. The authors present a case, concerning a young man, aged 20 years, died 11 months after the onset of the disease. The following peculiarities of the case are emphasized: 1) the clinical symptomatology and the evolution (myoclonus, lack of cerebellar impairment) could suggest the diagnosis of SSPE; 2) the EEG recordings showed epileptiform abnormalities, long latency diffuse periodic complexes and--during interferon therapy and simultaneously with a temporary clinical improvement--the appearance of short latency anterior periodic complexes. PMID- 1293992 TI - Cavernous angioma does not exist? AB - 12 cases of cerebral "venous angioma" are reported; pathological, clinical and radiological features of the lesion are reviewed. "Venous angioma" should be regarded as a developmental anatomic variation of the venous drainage system of the white matter. Its clinical significance is controversial, although it has been reported to cause hemorrhage, seizures, progressive neurological deficits, headaches. The clinical presentation of our patients was variable and, in some of them, dependent also on associated lesions. An hematoma was found in three patients, infarction in one and tumor in one. Angiography, CT and MRI demonstrated the typical appearance of the anomaly. Surgery was performed in one patient harboring a significant cerebellar hematoma and the coexistence of a cavernoma was pathologically confirmed. Venous developmental anomalies are often identified as the source of symptoms due to other conditions, that should be treated independently sparing the anomaly. PMID- 1293991 TI - Cerebral toxoplasmosis and AIDS. Clinical, neuroradiological and immunological findings in 15 patients. AB - Cerebral toxoplasmosis is the most common cause of focal CNS disease complicating AIDS and its incidence ranges from 3% to 40% of such patients. This opportunistic infection is generally due to reactivation of chronic toxoplasmosis as a consequence of severe immune deficiency. We present the clinical, neuroradiological and immunological findings of 15 AIDS patients with cerebral toxoplasmosis. All patients had focal neurological signs. CT-scan (13 cases) and NMR (2 cases) showed single or multiple mass lesions and edema. Serum IgG anti Toxoplasma antibodies were positive in 14 patients; CSF specific IgG were positive in 5 out of 7 studied patients, while serum and CSF specific IgM were negative in all subjects. The intrathecal synthesis of anti-Toxoplasma antibodies were high in all 7 patients. A presumptive diagnosis of cerebral toxoplasmosis is based on the focal cerebral signs and neuroradiological findings. It is more frequently confirmed by the improvement of the clinical and neuroradiological picture during the treatment with pyrimethamine-sulphadiazine or clindamycin. PMID- 1293993 TI - Upper airway muscles dysfunction and levodopa responsiveness in Parkinson's disease. AB - Pulmonary function tests were performed before and at different times after 250 mg L-Dopa in 12 patients with Parkinson's disease (PD). Six were de-novo patients, the other six patients had been taking L-Dopa over different periods. All patients had an abnormal basal flow-volume loop, which significantly improved only in de-novo patients. This improvement occurred early and was independent on improvement of neurological symptoms. The effect of L-Dopa on pulmonary function could be a useful test in differentiating PD from related extrapyramidal syndromes. PMID- 1293994 TI - [Huntington chorea. Clinical correlations and preliminary neuropsychological data]. AB - One of the cardinal features of Huntington's disease (HD) is the progressive cognitive deterioration. However, studies carried out on the neuropsychological profile in HD are discordant because there are differences in study designs, stage of disease and because of the coexistence of psychiatric disorders and cultural and educational background of subjects. Aim of this study is to relate the neuropsychological assessment with duration of illness and severity of motor impairment. Fourteen patients are given a neuropsychological battery, the results were statistically related to age and schooling. The data demonstrate very slow progression of cognitive deterioration without focal impairment of cognitive functions and without correlation with the severity of disease. PMID- 1293995 TI - Essential mental anorexia. Psychopathologic considerations and analysis of a case. AB - The AA. report the case of an anorexic girl, who could resume her evolutive process after an individual psychotherapy and parent's psychotherapy. In this way she could work out her defensive mechanisms and her EGO could internalize a previous menacing and persecutory maternal object. PMID- 1293996 TI - Antiepileptic drugs in pregnancy: late effects on the children's cognitive abilities. Preliminary data. AB - The authors report preliminary data on cognitive development of 57 children, perspectively followed, who were exposed to antiepileptic drugs in utero for maternal epilepsy. Cognitive impairments are associated with other risk factors in 5 cases, so that a direct AEDs responsibility is not easy to prove. PMID- 1293997 TI - THINKable, a computerized cognitive remediation. First results. AB - We have carried out the first study in Italy on the cognitive remediation by a new computerized system developed by IBM and called THINKable. Statistical analyses revealed that on some measures there was a significant improvement in the level of performance of the subjects at the time of the posttreatment assessment compared with the pretreatment assessment. Disorders of memory and higher cognitive functioning improved by structured retraining, independently of attention. Improvement has been matched by changes in the patients real-word functioning. Senile patients also took advantage from cognitive training. They were already followed before as outpatients and had no spontaneous recovery. The role of personal computers in neuropsychological training is discussed. PMID- 1293998 TI - Progress and controversies in neuropsychology of memory. AB - In the first part of this paper we discuss some of the most important areas of progress and of controversy in the field of memory functions and of memory impairment. Three main issues are taken separately into account: (1) the fractionation of memory into a number of sub-systems and the relationships existing among these subsystems; (2) the main theories of amnesia and the mechanisms underlying memory disorders; (3) the main anatomoclinical forms of amnesia and the brain structures subserving various components of the amnesic syndrome. In the second part we shift from the basic research to the clinically oriented investigations, reporting the results of two studies that we have recently conducted on some aspects of memory disorders in dementia. In the first study we have shown that severity and qualitative aspects of amnesia can be used to distinguish the two most frequent clinical forms of dementia, namely the dementia of the Alzheimer's type (DAT) from the vascular forms of dementia. In the second study we have demonstrated that a fine grained analysis of memory impairment can help improving the most difficult differential diagnosis in this field, namely the distinction between DAT and depressive pseudo-dementia. PMID- 1293999 TI - Semantic paralexias facilitated by tachistoscopic reading in a patient with impairment of phonological recoding. AB - This study of a dyslexic patient supports the view that the level of impairment of the phonological route plays a role in the production of semantic paralexias. The patient's reading was based on a defective phoneme-to-grapheme transcoding, in spite of evidence that semantic information was available through non phonological routes. The hypothesis that the residual ability to carry out phonological recoding could block the production of semantic paralexias was confirmed by tachistoscopic reading, assumed to interfere with phonological recoding in this patient, that provoked a definite rise of this type of error. The relationship between the degree of damage of phonological route and the clinical expression of the syndromes of phonological dyslexia and deep dyslexia is also discussed. PMID- 1294000 TI - Are patients with constructional disorders different in visuo-spatial abilities? AB - Many authors hypothesized a linkage between the anatomical region of damage and the nature of constructional apraxia. In particular, the functional impairment of right brain damaged patients should consist in a visuo-spatial defect. However a large amount of researches have showed impaired visuo-spatial abilities in apraxic subjects respect to non-apraxics, but independently by the side of brain damage. In these researches constructional and visuo-spatial abilities have been often evaluated by methods not comparable among them. Aim of this paper is to verify the constructional performances of left and right brain damaged patients, utilizing exclusively the copy of geometric figures and tasks considered specific in detecting visuo-spatial disabilities. The experimental results show that both left and right brain lesions produce impairments of visuo-spatial abilities. Lastly, the utility of a cognitive approach of study is discussed. PMID- 1294001 TI - [Rehabilitative approach to ataxia]. AB - The author, after visiting the most common methods in use to value the ataxic patient, gives a video camera system as a good valuation device, good to give objective, complete and verifiable data. This kind of evaluation must offer the formulation of a personalized treatment plane and can demonstrate the improvements obtained during the treatment. PMID- 1294002 TI - Megadolichobasilar anomaly. Clinical and diagnostic considerations on 30 cases. AB - 30 patients with megadolichobasilar artery, explored by angiography, are reported; 23 among them were first studied by computerized tomography and 4 by magnetic resonance. From the clinical point of view, 9 had transient ischemic attacks or definitive ischemia, 7 had subarachnoid or intracerebral hemorrhage, and 7 had deficits of the cranial nerves; in the other 7 cases the condition was incidentally discovered as isolated asymptomatic anomaly or with other unrelated lesions. Among the patients with ischemic symptoms, vertebrobasilar insufficiency and pontine infarction were the most common clinico-radiological findings. Among the patients with intracranial hemorrhage, four had associated aneurysm or arteriovenous malformations. CT and MR allow a correct diagnosis of this anomaly. MR seems to be superior to CT in delineating the relationship of the anomalous artery with the nervous structures, and the coexisting pathology. PMID- 1294004 TI - Video analysis of DNA sequence homologies. AB - A method for the rapid quantitative analysis of dot blot assays is presented. A video camera, an NTSC compatible frame grabber board, and an AT personal computer are used to read photographic exposures of the assay plate. Image processing and image analysis techniques are used to calculate the orientation of the dot raster and then to compensate for the effect of variations in field illumination on measurements of local contrast. Local contrast (between dots and background) is an exponential function of the amount of hybridization between blotted DNA and complimentary oligonucleotide probes. The amount of hybridization between blotted DNA and oligonucleotide probes of known sequence is the criteria used to establish HLA-DR tissue types. Although the assay described here utilizes a chemiluminescent reaction, this algorithm may be used to read any assay that produces a rectangular raster of dots. PMID- 1294003 TI - Solid-phase method for the purification of DNA sequencing reactions. AB - A solid-phase method for the purification of the single-stranded DNA molecules produced in enzymatic sequencing reactions has been developed. A primer oligonucleotide is synthesized containing a biotin moiety at an internal position. This primer is utilized in enzymatic extension reactions, and the resulting products are bound to streptavidin-coated magnetic beads. Contaminating species such as protein, salts, template DNA, and unincorporated or degraded deoxy and dideoxy nucleotide triphosphates may be removed by washing the beads after immobilizing them in the sample tube with a fixed magnet. The resulting pure single-stranded DNA fragments are removed from the solid support by heating in 10 mM EDTA, 95% formamide, loading dye at 90 degrees C, and may then be directly loaded onto a polyacrylamide gel for sequence analysis. This method was used to investigate the effect of various contaminants upon DNA sequence data. PMID- 1294005 TI - Axial evolution of the negative glow in a hollow cathode discharge. AB - The purpose of these studies was to examine the axial evolution of the negative glow in a hollow cathode discharge. The time-average negative glow profiles along the central axis of a hollow cathode were recorded for 81 pulse widths over the range of 5-25 microseconds in increments of 0.25 microseconds at a constant interpulse delay of 206.4 microseconds. Subsequent numerical processing yielded the instantaneous negative glow profile. The negative glow was viewed through a mesh-covered slot along the length of the hollow cathode. The negative flow profiles were imaged using a vidicon video camera. A PC-based frame grabber digitized the video images and stored them for subsequent processing. PMID- 1294006 TI - Acousto-optic tunable filter as a polychromator and its application in multidimensional fluorescence spectrometry. AB - Acousto-optic tunable filter (AOTF) is an electronically driven dispersive device which operates on the principle of acousto-optic interaction in an anisotropic medium. Incident white light will be diffracted by the AOTF into a specific wavelength when a specific rf is applied to it. The diffracted light needs not be a monochromatic light. Multiwavelength light can be diffracted from the AOTF when several rf signals are simultaneously applied into the filter. Compared to conventional polychromators, advantages of this electronic AOTF polychromator include its ability to individually amplitude-modulate each wavelength of the diffracted multiwavelength light at different frequency. This is accomplished by individually and sinusoidally modulating each applied rf signal at the desired frequency. This feature makes it possible to develop a novel AOTF-based multidimensional fluorimeter in which the sample was simultaneously excited by two different wavelengths (514.5 and 488.0 nm) whose amplitudes were sinusoidally modulated at two different frequencies (100 and 66 Hz). Multicomponent samples, e.g., mixtures of rhodamine 6G and rhodamine B, were successfully analyzed using this novel fluorimeter and the developed data analysis. PMID- 1294007 TI - 252Cf plasma desorption mass spectrometry in the synthesis of porphyrin model systems. AB - 252Cf plasma desorption mass spectrometry has been used in the characterization of more than 100 synthetic porphyrins ranging in mass from 614 u for tetraphenylporphyrin to over 2000 u for some porphyrin model systems. In virtually every case, 252Cf plasma desorption mass spectrometry yielded an intense ionized molecule ion [M.+ and/or (M+H)+], irrespective of the groups appended to the porphyrin. The appended groups include carboxylic acids, amides, imides, chloroacetamides, Fmoc-protected amino acids, aromatic amines, nitriles, alkynes, alkenes, esters, active esters, benzyl ethers, acetals, dithioacetals, ketones, imines, phenols, quinone, hydroquinone, ferrocene, cyanine dyes, trimethylsilyl protecting groups, nitro groups, and combinations of these functionalities. Metalloporphyrins and porphyrin-porphyrin dimers are also analyzed with ease. Resolved isotopic peaks were observed for porphyrins with molecular weights below 1000, and unresolved isotopic peaks yielding average masses were observed for porphyrin compounds with higher molecular weights. The limited resolution in the higher molecular weight range does not lessen the utility of the method because the observation of the molecule ions [M.+ and/or (M+H)+] provides unambiguous evidence concerning the success of the synthesis. The 252Cf plasma desorption mass spectra of porphyrins are not complicated by chemical transformations. This method is ideally suited for rapid analysis of synthetic porphyrins and provides a powerful tool for chemists engaged in the synthesis of complex organic molecules. PMID- 1294008 TI - Capillary ultrafiltration: in vivo sampling probes for small molecules. AB - Capillary ultrafiltration is a novel sampling method convenient for low molecular weight substances in living biological systems. By application of a negative pressure across a hydrophilic membrane capillary, small molecules are actively "pulled" across the membrane and collected. By elimination of large molecules and cellular matter, the ultrafiltrate collected is well suited for further analysis by liquid chromatography, capillary electrophoresis, or mass spectrometry. Ultrafiltration probes (UF probes) provide a simple means to obtain a small volume sample from subcutaneous tissue, blood, saliva, or any other biological fluid in vivo. The dependence of recovery on flow rate, temperature, membrane dimensions, and vacuum magnitude are considered. The relative merits of capillary ultrafiltration probes and microdialysis probes are considered. UF probe applications presented include in vivo monitoring of drug disposition in human saliva and in the subcutaneous space of awake, freely moving rats. PMID- 1294009 TI - Determination of intracellular species at the level of a single erythrocyte via capillary electrophoresis with direct and indirect fluorescence detection. AB - Intracellular contents reflect the specific history of a cell including innate physiological heterogeneity as well as differing levels of exposure to environmental influences. A method capable of analyzing a variety of species from within a single human erythrocyte is demonstrated. Guided by a microscope, individual cells can be drawn into open capillaries of 10-microns i.d. On contact with a low ionic strength buffer solution, the cell lyses and releases its intracellular fluid. The ionic components are then separated by capillary electrophoresis. For glutathione, microderivatization with a fluorescent reagent can be accomplished in vitro with monobromobimane. The effects of extracellular oxidizing and reducing agents on the glutathione levels can thus be followed. For sodium and potassium, or any other ionic species, charge displacement of a fluorescent cation results in indirect fluorescence detection. The two detection modes are suitable for intracellular components present at low-attomole and sub femtomole levels, respectively. PMID- 1294010 TI - Derivatization in trace organic analysis: use of an all-glass conical reaction vial. PMID- 1294011 TI - [Glycoprotein hormones, glycosylation and biological activity]. AB - Glycoprotein hormones LH, FSH, TSH and hCG are heterodimeric molecules: each contains two subunits, a common alpha and a unique beta subunit. Each subunit bears one or two Asparagine linked carbohydrate moieties which have a biantennary complex-type or hybrid-type structure. Different technical methods as deglycosylation or molecular biology techniques have been used to study the role of carbohydrate residues in hormonal bioactivity. The carbohydrate chains are not directly involved in receptor binding events but their mechanisms of action is not fully understood. Two hypotheses are frequently emphasised: a conformational role or an involvement in the coupling of the receptor-adenylate cyclase system. At the post receptor level carbohydrate chains modulate the bioactivity in two ways: a global regulation following an all-or-none mode and slight one. The removal of the carbohydrate moieties leads to a loss of the in vitro hormonal activity. The results observed are dependent of the deglycosylation techniques and the bioactivity tests used. Hormone's deglycosylation reduces their capacity of production of cAMP and, to a lesser extent, their steroidogenic power. Deglycosylated hormones are antagonists to negative hormones although deglycosylated hCG has some agonist properties in vivo. Microheterogeneity of the glycoprotein hormones is due to slight variations in sialic acid and/or sulfate content. Glycoprotein hormones exist as several isoforms which differ in biological potency. Alkaline isoforms (less sialylated ones) are the most biologically active in vitro but have a short half live in vivo; acid isoforms are less active in vitro but have a longer circulatory half live. The polymorphism of glycoprotein hormones is a highly regulated process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294012 TI - [Structure an functions of IgG subclasses]. AB - This review first deals with IgG subclasses according to the aspects that ascribe them their common class properties: general structure, enzymatic cleavage, synthesis, Gm allotypes. Then the subclass specific characteristics are described, comparing the main structural features (domains, hinge, disulfide bridges, kappa/lambda ratio). The IgG subclasses are further compared according to their effector functions, stressing those resulting from structural differences: classical pathway of complement activation, binding to Fc receptors, to protein A and to rheumatoid factors. Finally, a survey of the prolific works about antibody functions of IgG subclasses, allows a glimpse of the wide possible applications in this field. PMID- 1294013 TI - [Interlaboratory tests: completion of a method of aluminum assay in serum by electrothermal atomic absorption spectrometry]. AB - After carrying out a prior analysis of published literature, the members of the SFBC trace-elements study group present an interlaboratory trial on the measurement of aluminum in serum using electrothermal atomic absorption spectrometry. The means of measurement chosen, following methods reliability criteria, was the use of a standard addition calibration of the samples diluted 1/5 in nitric acid 0.02 mol.l-1. Standard addition calibration was performed on two serums and gives acceptable results. Measurements are preferably carried out in 'tantalised' graphite tubes or pyrolytic tubes with platforms. However, when using graphite tubes, their quality must be checked because measurements can be seriously affected by poor quality tubes. PMID- 1294014 TI - Evaluation of bronchoalveolar lavage for the diagnosis of bacterial pneumonia in ventilated patients. AB - Fourty-six patients requiring mechanical ventilation and suspected of bacterial pneumonia were examined by fiberoptic bronchoscopy. Specimens recovered by bronchoalveolar lavage (BAL) and using a protected specimen brush (PSB) were quantitatively cultured and the results compared. An assessment of the percentage of cells with intracellular organisms present on cytocentrifuged preparations made from lavage fluid was made to evaluate the utility of this method in early diagnosis of pneumonia. BAL cultures made a correct diagnosis in 43 out of 46 patients and detected 10 false-negative cultures of the PSB. With a threshold of more than 3% of cells with intracellular bacteria, direct microscopic examination diagnosed bacterial pneumonia in 36 out of 46 patients and allowed appropriate antibiotherapy to be instituted earlier. These results demonstrate the ability of BAL to diagnose bacterial pneumonia in ventilated patients. PMID- 1294015 TI - Evaluation of five commercial tests: complement fixation, microparticle agglutination, indirect immunofluorescence, enzyme-linked immunosorbent assay and latex agglutination, in comparison to immunoblotting for Mycoplasma pneumoniae serology. AB - A panel of 68 serum specimens from 41 subjects exhibiting various immunological patterns to Mycoplasma pneumoniae as determined by detection of a 180 kDa protein in immunoblotting was used to compare five commercially available tests based on different methods: complement fixation test (CFT), microparticle agglutination (MAG), indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (Elisa), and latex agglutination (LA). The tests were performed according to the manufacturers' instructions. For the determination of immunity to M pneumoniae, the five tests were in good accordance with immunoblotting: sensitivity was 100% for all the five assays, specificity ranged from 95.6% (MAG) to 82.6% (Elisa) and overall agreement ranged from 98.2% (MAG) to 92.8% (Elisa). The comparisons of antibody rates obtained by the four quantitative tests (CFT, MAG, IFA, Elisa) showed correlation coefficients ranging from 0.87 (CFT-IFA) to 0.67 (CFT-Elisa). Six significant antibody rises demonstrated by immunoblotting patterns were detected by all the tests but Elisa in one case. As a whole, the commercial assays gave satisfactory results for routine determination of immune status to M pneumoniae: CFT was the cheapest test and MAG and LA were the easiest to perform. PMID- 1294016 TI - [Identification of Mycobacterium tuberculosis and Mycobacterium avium by non radioactive probes: evaluation of the Snap Syngene system]. AB - We evaluated an alkaline phosphatase-labeled oligonucleotide probe for the rapid identification of Mycobacterium tuberculosis and mycobacteria belonging to the M avium and M intracellulare complex (MAIS). Sixty-two strains of mycobacteria and eight strains belonging to related genera were studied. All M tuberculosis strains hybridized with the tuberculosis probe. All M avium and M intracellulare gave a strong signal with their probes. However the 3 M xenopi strains tested hybridized with all probes for MAIS complex. PMID- 1294017 TI - [Recommendations for the assay of glycated proteins by the so-called fructosamine method]. PMID- 1294018 TI - Structure and genetic engineering of antigens and antibodies: applications in immunoassays. PMID- 1294019 TI - [Antimalarial effect of n-hentriacontanol isolated from Cuatresia sp (Solanaceae)]. AB - The antimalarial activity of the fatty alcohol, n-hentriacontanol, isolated from the bolivian Solanaceae, Cuatresia sp, is investigated in vivo through a classical four-day suppressive test against Plasmodium berghei and P. vinckei in mice. This product markedly reduced the virulence of experimentally induced P. vinckei infection. n-Hentriacontanol belongs to a new class of antimalarial natural compounds to be exploited for therapeutic purposes. PMID- 1294020 TI - Interleukin-6 in psoriasis: expression and mitogenicity studies. AB - Interleukin-6 (IL-6) is a multifunctional cytokine which has been suggested to function as an autocrine mitogen in psoriatic epidermis. We report here the results of several experiments designed to further examine this hypothesis. Blot hybridization was unable to detect 1.3 kb IL-6 transcripts in RNA extracted from normal or psoriatic epidermal (keratome) biopsies, suggesting that IL-6 expression is very low in normal and psoriatic epidermis. Therefore, qualitative and semiquantitative PCR/Southern blot analyses were performed on keratome derived RNA, and revealed variable but significantly increased IL-6 mRNA levels in lesional psoriatic relative to normal tissue. To further examine the ability of normal human keratinocytes (NHK) to express IL-6, RNA was extracted from rapidly proliferating secondary NHK cultures. IL-6 transcripts were nearly undetectable by blotting in keratinocytes grown in low-calcium serum-free medium, but low levels could be induced by treatment with 1.8 mM CaCl2. IL-6 transcripts were strongly superinduced after cycloheximide treatment, suggesting that a labile protein regulates IL-6 mRNA levels in these cells. Finally, the mitogenic activity of IL-6 was examined in NHK under varying conditions of cell density and added growth factors. IL-6 did not stimulate high density keratinocyte growth in the presence or absence of other growth factors, but did stimulate clonal growth in epidermal growth factor (EGF)-deficient media at high concentrations (> or = 10 ng/ml). The proliferative effects of IL-6, but not of basic fibroblast growth factor, were abrogated by monoclonal antibodies directed against the EGF receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294021 TI - Phenotypic determination of T-lymphocytes responding to chemotactic stimulation from fMLP, IL-8, human IL-10, and epidermal lymphocyte chemotactic factor. AB - Human T lymphocytes were collected after they had migrated towards N-formyl methionyl-leukylphenylalanine (fMLP), rIL-8, human IL-10 (hIL-10), and epidermal lymphocyte chemotactic factor (ELCF). They were stained for determination of their phenotype by FACS analysis using anti-CD4, -CD8, -CD18, -CD45R0 and OPD4 antibodies. Human IL-10 increased the percentage of CD8+ T lymphocytes in the migrating cell population by 152% compared with cells migrating towards the medium and decreased the number of CD4+ T lymphocytes by 79%. ELCF increased the number of CD4+ T lymphocytes by 18%, and the number of CD45R0+ T lymphocytes by 52%, while the number of CD8+ T lymphocytes was decreased by 20%. rIL-8 increased the number of CD4+ T lymphocytes and decreased the CD8+ T lymphocytes. The distribution of the different subpopulations of T lymphocytes was not changed significantly by fMLP. The observed changes in the phenotypes did not occur when incubating T lymphocytes with the chemotaxins. Our observations demonstrate that individual chemotactic factors will attract specific subsets of T lymphocytes. They may help to explain the predominance of memory T lymphocytes (CD4R0+, CD4+) in allergic contact dermatitis and certain other skin diseases. They also confirm the results of a recent study, that showed hIL-10 to be selectively chemotactic for CD8+ T lymphocytes. PMID- 1294023 TI - UVA tanning devices interact with solar-simulated UV radiation in skin tumor development in hairless mice. AB - The carcinogenic effect of three UVA tanning sources was studied in lightly pigmented hairless mice. The three tanning sources (Bellarium-S SA-1-12, Philips TL 09R and Philips TL 10R) have different emission spectra, and emit different amounts of UVB. Radiation from the tanning sources was administered for 20 min/day, 5 day/week in daily doses equivalent to those used in suntan salons. The radiation was given alone or after 12 weeks of exposure to solar-simulated UV radiation (SOLAR UV) (10 min/day, 4 day/week; daily dose, 19.5 kJ/m2 UVA and 3.9 kJ/m2 UVB). Irradiation with Bellarium-S SA-1-12 for 47 weeks and Philips TL 09R for 74 weeks induced skin tumours in 20/20 and 13/20 of the animals, respectively. When irradiation with Bellarium-S SA-1-12 and PHilips TL 09R was administered after 12 weeks of SOLAR-UV exposure, a strong enhancement of SOLAR UV-induced photocarcinogenesis was observed (p < 0.001). Irradiation with Philips TL 10R was only slightly carcinogenic, and during 85 weeks of irradiation only one skin tumor appeared in a group of 20 mice. However, when irradiation with Philips TL 10R was administered after 12 weeks of exposure to SOLAR UV, an enhancement of SOLAR-UV-induced carcinogenesis was observed (p < 0.001). Our results suggest that the hazards of exposure to commercial tanning devices are increased when they are used after a period of natural sun exposure. Even tanning sources with a low carcinogenic potential are able to increase SOLAR-UV-induced carcinogenesis significantly. PMID- 1294022 TI - A two-colour flowcytometric study of cell kinetics and differentiation of human keratinocytes in culture. AB - Double histochemical staining followed by flow cytometric analysis was performed to determine whether involucrin synthesis is associated with a particular phase of the cell cycle. In low-calcium medium (0.1 mM) monolayer cultures the expression of involucrin was confined to about 8% of the total cell populations. When the concentration of calcium was increased to 1.8 mM, the percentage increased and the distribution pattern of the cell cycle changed. The addition of retinoic acid at concentrations in the range 10(-8) M to 10(-6) M to a high calcium medium induced a further increase. The greatest increase in involucrin expression (up to five-fold) occurred in both the G1/G0 and G2 + M phases, while S phase cells showed a two-fold increase. The results indicate that involucrin synthesis is induced by retinoic acid, which occurs at any stage of the cell cycle, even in the S phase. PMID- 1294024 TI - Effect of the dose of ultraviolet radiation on the pigment formation by human melanocytes in vitro. AB - Human melanocytes were cultivated under different conditions with phorbol ester (TPA), or with bovine pituitary extract (BPE). The cells altered their morphology with the different culture conditions. With TPA they were predominantly bipolar, while with BPE most of the cells had a dendritic cell shape. In order to investigate the effect of UV irradiation, the cells were irradiated with 50, 100 and 200 mJ/cm2 UVA/B. After irradiation with 200 mJ/cm2 UVA/B the cells cultured with TPA also showed a dendritic shape. We determined the tyrosinase activity, the cellular melanin content and the cell number 3 days after irradiation. In all cases the number of cells decreased depending on the UVA/B doses. In melanocytes we found a marked increase in tyrosinase activity and melanin content after irradiation with 200 mJ/cm2. The UV-induced effect on tyrosinase activity was higher in melanocytes cultured with BPE than in those cultured with TPA. The results were compared with two human melanoma cell lines. Only little pigment formation could be measured in the tested melanoma cell lines without change after UV irradiation. PMID- 1294025 TI - Stratum corneum sphingolipids and free amino acids in experimentally-induced scaly skin. AB - Stratum corneum sphingolipids are of particular importance in maintaining the water permeability barrier of mammalian epidermis. Free amino acids also play an important role in water retention in the stratum corneum. To clarify the way in which these substances affect scaly skin, stratum corneum sphingolipids and free amino acids collected from artificially-induced scaly skin were analysed. Scaly skin was induced by tape stripping. The total amount of sphingolipids was quantified by gas chromatography and five of sphingolipid fractions were isolated and quantified by thin-layer chromatography. Free amino acids were analysed using a high-speed amino analyser. The total amount of sphingolipid in scaly skin did not differ statistically from that in control skin. However, a significant change in the distribution of the five sphingolipid species was observed in scaly skin and the total amount of amino acids was decreased in scaly skin. These results suggest that the distribution of these five types of sphingolipid and the total amount of amino acids are responsible for scaly skin. PMID- 1294026 TI - The effect of 1,25(OH)2-vitamin D3 on Langerhans cells and contact hypersensitivity in mice. PMID- 1294027 TI - Ultrastructural localization of autoantigens of intercellular IgA vesiculopustular dermatosis in cultured human squamous cell carcinoma cells. PMID- 1294028 TI - [Results of a randomized, double blind prospective study of intravesical chemoprophylaxis with 2 drugs: adriamycin and mitomycin; and 2 ways of initiating the instillations: early and late. Effect on recurrence and progression]. AB - The results of a double blind prospective study comparing the chemoprophylactic effects of adriamycin and mitomycin C and two modes of instillation (early: 6 hours following transurethral resection; late: 7-14 days later) for superficial carcinoma of the bladder are presented herein. Since the minimum follow up is over 5 years, the effects on tumor progression and mortality achieved by each of the 4 arms of the protocol were also evaluated. Concerning tumor recurrence, early instillation of mitomycin and overall early instillation therapy achieved significantly better results (p < 0.01). No differences, however, were observed relative to tumor progression or mortality. PMID- 1294029 TI - [Cystometry in recurrent stress urinary incontinence]. AB - We reviewed the postoperative cystometries and clinical data of 33 patients with post-surgery recurrent stress urinary incontinence to determine the incidence of surgical failure and misdiagnosis. The results show that 63.6% of the cases were due to a technical failure. A second postoperative failure is likely to be due to an unstable bladder. PMID- 1294030 TI - [Laparoscopic testicular autotransplantation]. AB - The authors describe an experimental technique of endoscopic autotransplantation of the testis. Four trocars are utilized; one is placed at the level of the umbilicus, one in the right flank, another in the left flank, and one in the hypogastrium. Five or six cms of the epigastric vessels are dissected and sectioned. Then the spermatic vessels and released from the inguinal orifice up to their origin and sectioned. The testis is taken to the peritoneal cavity through the skin and the sustenaculum testis is sectioned. Both vascular pedicles are exteriorized through an incision at the level of the inguinal duct. Microvascular anastomosis is performed as in a routine procedure and the vessels are inserted into the abdomen again, the testis is taken to the scrotum and the inguinal duct is closed from inside. PMID- 1294031 TI - [Extracorporeal arterial reconstructive surgery in complex vasculo-renal pathology]. AB - Herein we describe a case of a 23-year-old male patient with severe hypertension that was refractory to medication, a hypoplastic left kidney and complex renovascular disease. Patient evaluation revealed stenosis of the right renal artery and saccular aneurysms of its three branches. Treatment with converting enzymes was discarded due to the risk of azotemia and the complex vascular disease advised against percutaneous transluminal angioplasty. He was therefore submitted to ex situ vascular repair (bench surgery) using the hypogastric artery with its three branches and autotransplantation in the right iliac fossa. The foregoing procedure achieved excellent results. The arterial pressure and overall renal function returned to normal 15 days postoperatively. In our view extracorporeal surgery is the procedure of choice in patients with complex renovascular disease involving the small branches of the renal artery. PMID- 1294032 TI - [Villous adenoma of urinary bladder. Report of a new case]. AB - We report on an 80-year-old female patient with a villous polyp of the bladder. We believe this lesion may correspond to an intermediate stage in the well known sequence of injury-metaplasia-dysplasia-carcinoma of the large intestine. Intestinal metaplasia in the bladder is a potentially malignant lesion. If villous adenomas are diagnosed early, before malignant transformation, simple excision can achieve cure. PMID- 1294033 TI - [Retroperitoneal abscess. Report of 2 cases]. AB - Two cases of retroperitoneal abscess that had recently been treated in our service are described. The primary infection was localized to the psoas muscle in one patient with a previous injury to the right lumbar region. The other case was secondary to an ascending urinary infection. Staph aureus were isolated in the first case and E. Coli in the second. The different clinical course and treatment of each case are described. PMID- 1294035 TI - [Pyo-urachal cyst]. AB - A case of infected and suppurating pyourachal cyst is described. The rarity of urachal pathology in the adult prompted us to report the present case. The clinical features, diagnosis and treatment of this urachal complication are discussed. PMID- 1294034 TI - [Inguino-scrotal bladder hernia]. AB - We report on a 61-year-old patient with massive scrotal herniation of the bladder and non-Hodgkin malignant lymphoma. We briefly describe this disease entity and its form of presentation, and discuss its diagnosis and treatment. PMID- 1294036 TI - [Renal cyst communicating with excretory tract: report of a case]. AB - Simple renal cyst communicating with the excretory tract is a rare complication frequently arising from obstructive uropathy. In most of the cases treatment continues to be conservative. PMID- 1294037 TI - [Adrenal myelolipoma: a new case. Review]. AB - We report a case of symptomatic myelolipoma with a good evolution at three and a half years' follow up. The clinical features and the diagnosis of this tumor type are discussed. In this case, as in most cases, CT proved to be the most useful in making the diagnosis. Like most of the cases, the patient was middle aged, obese and hypertensive. The etiology, pathogenesis, clinical features and diagnosis of this disease entity are reviewed. The treatment modalities utilized according to the specific features of each case are discussed. PMID- 1294039 TI - Surgical treatment of obstructive azoospermia. AB - The records of 325 azoospermic patients were reviewed. A total of 109 patients (33.5%) had obstructive azoospermia and 48 of them underwent surgical treatment. Three patients had vas deferens agenesia and underwent artificial spermatocele; 14 with epididymal obstruction were treated by an end-to-end microsurgical vasoepididymostomy; and 31 vasectomized patients were submitted to microsurgical reversal. There was no pregnancy in the spermatocele patients. In the vasoepididymostomy patients 60% became patent and 30% achieved pregnancy. In the reversal group 90% of patency and pregnancy rate of 80% were observed, in a mean follow-up of 21 months. The last 8 cases were treated with a biological glue and 7 showed patency and one pregnancy in a 3-month follow-up period. One was lost to follow-up. PMID- 1294038 TI - [Calcification of seminal vesicles and deferent duct]. AB - Herein we describe a chronic diabetic with calcification of both seminal vesicles and the deferent duct which had been disclosed by a plain film of the urinary tract and an IVP. Currently the foregoing condition can be considered to be pathognomonic of diabetes mellitus, although these patients generally do not present urological symptoms or signs. PMID- 1294040 TI - [Minimally invasive surgery of urologic complications in renal transplant recipients]. PMID- 1294041 TI - [Injection of autologous fatty tissue in the bladder submucosa: experimental study in swine]. AB - The results achieved by the use of inert materials via endoscopic injection for the treatment of urological pathologies have been disappointing. Furthermore, these materials are costly, carry the risk of migration and may not be tolerated locally. Autologous fatty tissue, however, is not costly and is tolerated better. The authors have conducted an experiment in the pig to evaluate the degree of resorption and persistence of autologous fat injected into the bladder submucosa. The results show that submucosal injection of autologous fat acts like an autograft and persists as mature fatty tissue. The degree of resorption and/or steatonecrosis is directly related to the amount injected; the smaller the amount used the better the results. PMID- 1294042 TI - [Our caseload in Fournier's disease]. AB - We reviewed the records of 17 cases of Fournier's gangrene that had been diagnosed and treated in the Urology Service of the Marques de Valdecilla Hospital from 1982-1991. The series comprised male patients aged 32 to 77. Eleven cases (64.7%) were due to a known cause, above all infection. Most of the patients had factors that predisposed to the development and progression of the disease, predominantly diabetes mellitus (5 cases, 29.4%). The clinical features frequently corresponded to those of acute infection, with high fever, chills, pain, nausea and vomiting that could progress to a septic state. The local symptoms and signs included pain, swelling, erythema and necrosis, depending on the compromised area. Infection was usually caused by Gram-negative bacteria, particularly E. coli, although Gram-positive bacteria and anaerobes have been observed. Mixed bacterial infections have also been observed. Treatment must be instituted early using a combination of broad spectrum antibiotics that cover both aerobes and anaerobes, and wide surgical debridement of the compromised area. In some cases hyperbaric oxygen therapy may be warranted. The disease continues to be severe. In the present series, the outcome was favorable in 12 cases (70.5%) and there were 5 deaths (29.4%). PMID- 1294043 TI - [Sclerosing therapy of testicular hydrocele with tetracycline]. AB - Twenty-six patients, aged 38 to 78 years, with testicular hydrocele were treated by aspiration, punction and tetracycline instillation. The cure rate was 79%. Inflammation of the scrotum was observed in all of the cases. Due to recurrence two patients underwent surgery, which revealed a hematocele. PMID- 1294044 TI - [Histogenesis of isthmic nodular salpingitis]. AB - Nodular salpingitis of the isthmus is a clinicopathological entity related to what is classically referred to as interstitial adenomyosis. These two lesions are due to the same aetiopathogenic process and result from inflammatory proliferation of the tubal epithelium with formation of pseudoglandular ducts. The only difference between the two is that one is ensheathed by a fine network of mesonephric muscle fibres and the other is surrounded by a thick layer of myometrial muscle fibres. These two lesions should be grouped under the same heading: nodular salpingitis. The term adenomyosis is incorrect due to the absence of endometrial glandular ducts and stroma in these lesions. Nodular salpingitis of the isthmus should be distinguished from tubal endometriosis, which is part of the clinical expression of extrauterine endometriosis. In particular, this lesion must be distinguished from interstitial endometriosis which, for some authors, corresponds to colonisation of the tubal mucosa by endometrium and, for others, to metaplasia of the tubal mucosa. PMID- 1294045 TI - [Primary and secondary carcinomas of the thyroid gland with systematic discovery. Apropos of hundred thyroid glands removed at autopsies and review of the literature]. AB - One hundred thyroids from autopsies performed in a Cancer Center were sectioned at 4 mm intervals. Each slice was processed to obtain one or several sections for histologic examination. Five primary microcarcinomas and ten secondary clinically unknown carcinomas were found. This study and the review of the literature confirm that the high prevalence rate of microcarcinomas, most of them papillary, in autopsies does not agree with the clinically diagnosed carcinoma rate. Tumors greater than 5 mm in diameter may sometimes be aggressive. Intrathyroid metastases are relatively frequent in cancerous dissemination observed in autopsies, but raise problems when they precede the primary tumor or are revealed on surgical samples a long time after because of a slow development. The authors emphasize the importance of differential diagnosis between primary and secondary tumors and the value of immunohistochemistry for histological diagnosis. PMID- 1294046 TI - [Comparative study of the expression of CEA and a myelomonocytic antigen (CD15) in serous effusions using two monoclonal antibodies NEO 723 and Leu M1]. AB - A comparative study of the reactivity of two monoclonal antibodies (MAb), NEO 723 (anti-CEA) and Leu M1 (CD15) was performed by immunocytochemistry on sixty five reactive effusions and sixty two neoplastic effusions, fifty eight due to metastases from carcinomas, two due to disseminations of sarcoma and two due to malignant mesotheliomas. The study of the expected reactivity of NEO 723 and the cross-reactivity of Leu M1 on exfoliated neoplastic cells in effusion fluids showed that the sensitivity of NEO 723 was superior to that of Leu M1 for the detection of carcinomatous metastases, as 78% reacted with NEO 723 versus 38% with Leu M1. Among the positive cases, the mean number of reactive cells was twice as high with NEO 723, while only three of the carcinomas no expressing CEA reacted with Leu M1. The study of the reactivity of benign and malignant mesothelial cells with these two antibodies also confirmed the absence of labelling of these cells. Thus, despite a good specificity for carcinoma, the combination of these two antibodies provides only a minor gain in diagnostic sensitivity (+5%) compared with the use of an anti-CEA antibody alone and a loss of sensitivity (-5%) compared with the combination of an anti-CEA and an anti-EMA antibodies. These results appear to justify the suppression of Leu M1 from the first panel of antibodies screening for carcinomatous cells in favour of a combination of anti-CEA and an anti-EMA antibodies. However, Leu M1 may be useful as a second-line test in order to define the primary tumour responsible for the effusion. PMID- 1294047 TI - [Epidemiology of tumors of the testis]. AB - Testicular tumours are rare tumours affecting young adults (75% of tumours are diagnosed between the ages of 25 and 40 years). The descriptive epidemiological study of the data of the literature reveals a considerable improvement in the prognosis of testicular cancers, particularly since the introduction of cisplatin in the 1980. An epidemiological study conducted on a series of 200 testicular tumours treated at Val-de-Grace military hospital between 1979 and 1989 confirms this improvement with a mortality rate of 7.5% for all stages and histological types combined, with a follow-up of 2 to 12 years. PMID- 1294048 TI - [Pathologic anatomy of tumors of the testis]. AB - Pathological examination of testicular tumours demonstrates the heterogeneity of the histological types encountered. Germ cell tumours, with one or several components, represent 95% of all testicular tumours. The distinction between these various types is always based on morphological criteria, but may also be facilitated by the use of immunolabelling techniques on fixed sections. The local and regional extension and the distinction between seminomatous and non seminomatous germ cell tumours are important criteria in the subsequent therapeutic strategy. At the present time, there is no consensus concerning the selection of other histoprognostic criteria, which may be observed in the primary tumour it its metastases. Residual masses also have a variable histology and their pathophysiology is sometimes difficult to interpret. PMID- 1294049 TI - Vaginal metaplasia of the bladder associated with ectopic ureterocele. A clinicopathologic study of two cases. AB - We report two cases of vaginal metaplasia associated with ectopic ureterocele with complete ureteric duplication. The theories proposed to explain this metaplastic change are briefly reviewed. This previously unreported association with ectopic ureterocele suggests that this may an example of heteroplasia, and that this relationship could be more than casual. PMID- 1294051 TI - A survey of hospital attendances for skin disease in Perth. AB - Analysis of hospital attendances for skin diseases is not a true prevalence study; however, it gives valuable information to the dermatologist. A two week study of hospital attendances at the skin clinics in three major hospitals in Western Australia was conducted. The most common conditions encountered were solar keratoses, psoriasis, malignant tumours and dermatitis. These results are similar to those of a population based prevalence study carried out in Western Australian in 1979. PMID- 1294050 TI - A case of perineurioma with prominent myxoid changes. AB - A perineurioma with prominent myxoid changes is presented. The patient, a 41 year old woman, presented with a small skin nodule on her back. Light microscopy revealed subtle cellular whorls within a myxoid background. Immunohistochemistry showed epithelial membrane antigen positivity. In contrast, S-100 protein, common leukocyte antigen, vimentin and AE1-AE3 cytokeratin were negative. PMID- 1294052 TI - Skin disease in general practice. AB - Out of 336 consultations in general practice 52 (15%) concerned a dermatological problem. Sun related problems, eczema/dermatitis and infection were encountered most frequently. PMID- 1294053 TI - Australian Dermatopathology Society. Recurrent vesicular lesions on sun exposed skin. PMID- 1294054 TI - Modern treatment of lymphoedema. I. Complex physical therapy: the first 200 Australian limbs. AB - Complex Physical Therapy (CPT) is discussed and its principles outlined. CPT involves: 1. skin care, 2. a special lymphatic massage, 3. compression bandaging and (later) garments, 4. special exercises which supplement the massage. CPT was used on 78 patients with postmastectomy lymphoedema (17 with Grade 1 and 61 with Grade 2). There were significant differences between the Grades. In the first four-week course the mean Grade 1 was reduced from 121% of normal to 107% (the mean change in the oedema was 103% of its initial value), and Grade 2 from 153% to 123% (with a mean change in oedema of 60%). All these were very highly significant. Over the next year there was a small, but very significant, decrease in the percentage of oedema. A further four-week course resulted in significant, and similar, reductions in the residual oedema. CPT was used to treat 128 lymphoedematous legs; 22 were Grade 1 lymphoedema, 84 were Grade 2 and 19 were elephantitic (Grade 3). After the first course of CPT the mean losses were: 1.1, 1.3 and 3.7 litres, respectively (all very significant). Over the next 11 months there were significant further reductions for all legs and in the amount of oedema of the unilateral legs. Some patients had a second course of CPT with similar reductions in the remaining oedema to that after the first course. PMID- 1294055 TI - Modern treatment of lymphoedema. II. The benzopyrones. AB - The benzo-pyrones reduce all high-protein oedemas, including lymphoedema and elephantiasis, by increasing the numbers of macrophages and their normal proteolysis. Thus they remove the excess protein, and thereby the oedema which is caused by it. They also remove the stimulus it provides for chronic inflammation and fibrosis, and its action as a culture medium for bacteria. Coumarin (5,6 benzo-[alpha]-pyrone, 56 BaP) and oxerutins (HR, O(beta-hydroxy-ethyl)-rutosides) have been used in many clinical trials on a variety of high-protein oedemas. Four such trials are summarised here: on lymphoedema and elephantiasis (from many causes in Australia, and filaritic in India and China). The drugs reduced these much more slowly than adequate physical therapy, but they did reduce them. About half the excess volume was removed over six months in the Australian trials. In India and China similar rates were achieved with lymphoedema, but elephantiasis reduced at a slower rate. The benzo-pyrones convert a slowly worsening condition into a slowly improving one. No compression garments are necessary. In addition, the drugs considerably reduce the number of attacks of secondary acute infection, reduce the deformities of elephantiasis and considerably improve the patients' comfort and mobility. They may be taken orally, or applied topically, have very low toxicities and only few, minor side-effects. They are useful in many other forms of high-protein oedema, and improve the results of physical therapy for lymphoedema. PMID- 1294056 TI - The effect of bacterial colonization on venous ulcer healing. AB - To determine the effect of bacterial colonization on venous ulcer healing, 82 patients with 100 venous ulcerated limbs were each studied prospectively for six months. Despite bacteriological swab results, topical or systemic antibiotics were not administered unless cellulitis supervened. Initial ulcer size, length of ulcer history and time to complete healing of colonized and uncolonized ulcers were determined and compared. Organisms were cultured from 83 limbs prior to commencement of treatment, the commonest isolates being Staphylococcus aureaus (48%), mixed coliforms (28%), Pseudomonas aeruginosa (21%) and anaerobes (17%). When compared with ulcers with no bacterial growth, colonized ulcers were of longer duration (p [symbol: see text] 0.01), had a larger initial size (p [symbol: see text] 0.001) and had significantly longer healing time (p [symbol: see text] 0.001). When analysed individually beta-haemolytic streptococci, anaerobes, Staphylococcus aureus and coliforms were associated with delayed healing. Delayed healing was not found with Pseudomonas aeruginosa, although pseudomonas-colonized ulcers were significantly larger and of longer duration than uncolonized ulcers. Bacterial colonization is associated with delayed venous ulcer healing. To further clarify the pathogenicity of colonizing bacteria, however, the effect of their eradiction on healing of venous ulcers needs to be established. PMID- 1294057 TI - Treatment of basal cell carcinoma with intralesional interferon alpha: a case report and literature review. AB - We report the case of a 76 year old man with three ulcerated basal cell carcinomas on his lower limbs. He was considered unsuitable for surgical therapy and was treated by intralesional interferon alpha-2b (Intron A) injections. Twenty months post therapy two of the three treatment sites remain clinically cured. Recurrence occurred at the site which received the smallest total dose of interferon. A review of the therapeutic trials of interferon alpha for basal cell carcinoma is presented. We conclude that interferon alpha-2b is a useful agent for treatment of basal cell carcinoma in selected patients. PMID- 1294058 TI - Carbon dioxide laser treatment of periungual and subungual viral warts. AB - This is a retrospective study of the cure rates of forty patients with subungual and periungual viral warts treated with carbon dioxide laser vapourisation (total of 69 lesions). 70.6% (48/68) lesions had failed treatment with cryotherapy and/or electrocautery treatment previously. 20/68 were treated with CO2 laser vapourisation as a first line treatment. The overall cure rate over 10 months follow-up period was 57.4% (39/68). Most recurrences (24/25) occurred within the first 3 months of vapourisation. The carbon dioxide laser vapourisation cure rate for warts in which previous cryotherapy and/or electrocautery had failed was 47.9% whereas those treated with carbon dioxide laser vapourisation as a first line treatment had a cure rate of 80% (p = 0.043). Subungual warts responded slightly better with a cure rate of 64.7% compared with periungual warts (54.9%) (n.s.). The carbon dioxide laser vapourisation cure rate for recurrent subungual and periungual warts (which failed previous carbon dioxide laser vapourisation) was 73.3% (11/15). Our findings appeared to indicate that periungual and subungual warts can be eradicated by CO2 laser vapourisation. Recurrent warts can be effectively eradicated by further vapourisation. Recalcitrant periungual and subungual warts which have previously failed to respond to cryotherapy and/or electrocautery can be effectively eradicated with CO2 laser vapourisation. PMID- 1294059 TI - Cutaneous cryptococcosis: recurrence following oral fluconazole treatment. AB - A case of recurrent cutaneous cryptococcosis in an immunocompromised patient is described. The patient presented with a non-healing cutaneous ulcer due to infection with Cryptococcus neoformans. Extensive investigation failed to reveal any evidence of associated systemic cryptococcosis. Treatment with oral fluconazole resulted in complete resolution of the ulcer but after several months a second cutaneous cryptococcal lesion appeared, strongly suggesting dissemination from an underlying systemic focus. This case illustrates the hazards associated with making a diagnosis of isolated cutaneous cryptococcosis and the necessity for prolonged follow-up of patients who present in this way. PMID- 1294060 TI - Hypomelanosis of Ito: report of two cases. AB - Hypomelanosis of Ito is an uncommon syndrome where bizarre, systematized hypopigmentation is often associated with neurological and other non-cutaneous abnormalities. We report two cases, one which was associated with laryngomalacia and sudden death (in which the parents were consanguineous), and one which was associated with episodes of loss of consciousness. PMID- 1294061 TI - Cognitive impairment after ECT in patients with Parkinson's disease and psychiatric illness. PMID- 1294062 TI - Electrogenic properties of the cloned Na+/glucose cotransporter: II. A transport model under nonrapid equilibrium conditions. AB - The results of the accompanying electrophysiological study of the cloned Na+/glucose cotransporter from small intestine (Parent, L., Supplisson, S., Loo, D.D.F., Wright, E.M. (1992) J. Membrane Biol. 125:49-62) were evaluated in terms of a kinetic model. The steady-state and presteady-state cotransporter properties are described by a 6-state ordered kinetic model ("mirror" symmetry) with a Na+:alpha MDG stoichiometry of 2. Carrier translocation in the membrane as well as Na+ and sugar binding and dissociation are treated as a function of their individual rate constants. Empty carrier translocation and Na+ binding/dissociation are the only steps considered to be voltage dependent. Currents were associated with the translocation of the negatively charged carrier in the membrane. Negative membrane potential facilitates sugar transport. One numerical solution was found for the 14 rate constants that account quantitatively for our experiment observations: i.e., (i) sigmoidal shape of the sugar-specific current-voltage curves (absence of outward currents and inward current saturation at high negative potentials), (ii) Na+ and voltage dependence of Ksugar0.5 and isugarmax, (iii) sugar and voltage dependence of KNa0.5 and iNamax, (iv) presteady-state currents and their dependence on external Na+, alpha MDG and membrane potential, and (v) and carrier Na+ leak current. We conclude that the main voltage effect is on carrier translocation. Na+ ions that migrate from the extracellular medium to their binding sites sense 25 to 35% of the transmembrane voltage, whereas charges associated with the carrier translocation experiences 60 to 75% of the membrane electrical field. Internal Na+ ion binding is not voltage dependent. In our nonrapid equilibrium model, the rate-limiting step for sugar transport is a function of the membrane potential, [Na]o and [alpha MDG]o. At 0 mV and at saturating [Na]o and [alpha MDG]o, the rate-limiting step for sugar transport is the empty carrier translocation (5 sec-1). As the membrane potential is made more negative, the empty carrier translocation gets faster and the internal Na+ dissociation becomes increasingly rate limiting. However, as [Na]o is decreased to less than 10 mM, the rate-limiting step is the external Na+ ions binding in the 0 to -150 mV potential range. At 0 mV, the external Na+ dissociation constant KNa' is 80 mM and decreases to 24 mM at -150 mV. The external sugar dissociation constant KNaS' is estimated to be 200 microM and voltage independent. Finally, the internal leak pathway (CNa2 translocation) is insignificant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1294063 TI - ST-waveform analysis of the fetal electrocardiogram could reduce fetal blood sampling. PMID- 1294064 TI - Breech delivery and epidural analgesia. AB - OBJECTIVE: To examine the effect of epidural analgesia on the progress and outcome of spontaneous labour in women with a singleton breech presentation at term (greater than or equal to 37 weeks). DESIGN: A retrospective study. SETTING: Data Bank, Aberdeen Maternity Hospital. SUBJECTS: 643 women (273 primiparae and 370 multiparae) with a singleton breech presentation and spontaneous onset of labour at term. OUTCOME MEASURES: Duration of labour; augmentation of labour with oxytocin infusion; caesarean section rates. RESULTS: Epidural analgesia was associated with a significantly increased need for augmentation of labour with oxytocin infusion (P less than 0.001) and longer duration of labour (P less than 0.001), irrespective of parity. Comparing women who had epidural analgesia with those who did not, there was no significant difference in caesarean section rates in the first stage of labour in primiparae (odds ratio 1.79; 95% CI 0.88-3.63) or multiparae (odds ratio 0.97; 95% CI 0.48-1.96). Epidural analgesia was associated with a significantly increased likelihood of caesarean section in the second stage of labour, both in primiparae (odds ratio 5.43; 95% CI 2.46-11.95) and multiparae (odds ratio 5.37; 95% CI 2.07-13.87). The increased likelihood of caesarean section in the second stage in primiparae with epidurals was independent of the extent of cervical dilatation (less than 3 cm or greater than or equal to 3 cm) on admission. However, in multiparae with epidurals, the difference in second stage caesarean section rate was significant only when initial cervical dilatation was less than 3 cm (odds ratio 3.65; 95% CI 1.14 11.65). CONCLUSION: Epidural analgesia was associated with longer duration of labour, increased need for augmentation of labour with oxytocin infusion and a significantly higher caesarean section rate in the second stage of labour. PMID- 1294065 TI - Pre-employment colour vision testing. AB - Male candidates (1020) for employment in occupations that required discrimination of colour were subjected to the Ishihara test and two trade tests of colour perception, the Giles Archer Lantern test and the Electricity Supply Industry (ESI) wire test. One hundred candidates failed the Ishihara test, 61 of the 100 passed both trade tests; 16 of the 100 passed the wire test alone and 7 of the 100 passed the lantern test alone but only 16 failed all 3 tests. Seventy-seven of the 84 who passed some part of their colour perception assessment were offered employment appropriate to their colour vision ability. Eleven of the 16 who passed the wire test alone and 3 of the 6 who passed the lantern test alone successfully entered employment. The Ishihara test, whilst being a useful screening test, is not sufficient on its own as a test of suitability for employment; one or more trade tests should be administered before rejecting candidates who fail it. PMID- 1294066 TI - Schizophrenia following pre-natal exposure to influenza epidemics between 1939 and 1960. AB - We examined the relationship between the dates of births of schizophrenic patients admitted to hospitals for the first time in England and Wales between 1970 and 1979, and the occurrence of influenza epidemics between 1939 and 1960. Our results indicate that exposure to influenza epidemics between the third and seventh month of gestation is associated with schizophrenia in adult life. The hypothesis that maternal viral infection is an important cause of schizophrenia can explain many aspects of the enigmatic epidemiology of the condition. PMID- 1294067 TI - Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction. AB - From a study of 526 patients having automatic ECG analysis, criteria were established which diagnosed acute evolving Q wave myocardial infarction with 71% sensitivity and 98% specificity. Specificity was 100% when patients with known previous Q wave infarction were excluded. In pre-hospital practice the high sensitivity and specificity were maintained. This method appears appropriate, when other criteria are met, for paramedic-initiated pre-hospital thrombolysis with remote supervision of a cardiologist by telephone. PMID- 1294068 TI - Femoral and popliteal arteries: reanalysis of results of balloon angioplasty. AB - The author presents an alternative statistical analysis of the results of the University of Toronto series of percutaneous transluminal angioplasty (PTA) of the femoral and popliteal arteries (n = 254). After recalculation of the data with the Kaplan-Meier method, the postprocedure success rate ranged from 88.8% +/ 2.0 at 1 month to 35.7% +/- 4.8 at 6 years. With Cox multiple regression analysis, the type of femoropopliteal lesion and the runoff were the variables that were useful to predict late results. For stenoses with good runoff, the success rate was 53% at 5 years; with poor runoff, 31% at 5 years. For occlusions with good runoff, the success rate was 36% at 5 years; with poor runoff, 16% at 5 years. In initially successful cases, ongoing clinical success at 1, 3, and 5 years was better in patients with good runoff at the time of PTA than in those with poor runoff. Now that more recent studies have documented improved technical success in femoropopliteal PTA, a comparative study of the relative safety, long term clinical efficacy, and cumulative cost of PTA versus surgery seems warranted. PMID- 1294069 TI - Who's in charge? PMID- 1294070 TI - Rapid diagnosis of testicular tumour. PMID- 1294071 TI - Intravenous volume replacement: which fluid and why? PMID- 1294073 TI - Coping with extraperitoneal insufflation during laparoscopy: a new technique. AB - For most laparoscopists, pneumoperitoneum is essential before introducing a trocar into the peritoneal cavity. Extraperitoneal insufflation is one of the most common complications of laparoscopy; it is difficult to correct and may result in abandonment of the procedure. A technique for dealing with extraperitoneal insufflation is described. We have used this technique successfully on 11 consecutive patients. The gynecologist uses the view created by the extraperitoneal gas to place the Veress needle correctly into the peritoneal cavity. Insufflation proceeds under direct vision; the peritoneum will rise and obliterate the extraperitoneal space. This technique may be useful particularly when alternative methods are contraindicated. PMID- 1294072 TI - Relinquishment of premarital births: evidence from national survey data. AB - According to 1982 and 1988 NSFG data, unmarried white women are far less likely than they were in the early 1970s to place their children for adoption. The levels of relinquishment among black women have remained low throughout this period, and relinquishment among Hispanic women may be virtually nonexistent. Multivariate analysis of the determinants of relinquishment among unmarried non Hispanic white women suggests that having a well-educated mother, being in school at the time of conception, having no labor force experience, and being older are positively associated with placing a child for adoption. Sons were found to be less likely to be relinquished than daughters. PMID- 1294074 TI - Denture stomatitis--a review of the aetiology, diagnosis and management. AB - Denture stomatitis is a common recurring problem of the denture wearers. The aetiology of the disease includes infection, trauma and probably a defect in the host defence mechanism. Current thinking suggests an interplay of most of these factors in the pathogenesis of the disease. The extent of interplay of these factors is still a controversy. Candida albicans has been implicated as the causative organism. However, in the light of recent research it is debatable if it is the only causative organism. Recently, cases resistant to antifungal therapy have been reported. In such cases other micro-organisms have been isolated. At the moment, comprehensive management includes meticulous denture hygiene together with anti-fungal or antibacterial therapy and correction of denture faults. PMID- 1294075 TI - Breast implant materials: sense and safety. AB - Cosmetic breast augmentation, and post-mastectomy breast reconstruction surgery using synthetic implants, have become established in surgical practice over more than 20 years. The operative technique for implant placement have changed somewhat during this time, as many different implant presentations have become available, but the same basic materials have remained in use. We have reviewed the present state of knowledge about breast implant materials with particular reference to the possible connection between polydimethylsiloxane and polyurethane to the so-called "Human Adjuvant Disease", and to carcinogenesis. Problems related to capsular contracture and mammography are also discussed. PMID- 1294076 TI - Fatal and near-fatal anaphylactic reactions to food in children and adolescents. AB - BACKGROUND AND METHODS: Reports of fatal or near-fatal anaphylactic reactions to foods in children and adolescents are rare. We identified six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation. All the cases but one occurred in one of three metropolitan areas over a period of 14 months. Our investigations included a review of emergency medical care reports, medical records, and depositions by witnesses to the events, as well as interviews with parents (and some patients). RESULTS: Of the 13 children and adolescents (age range, 2 to 17 years), 12 had asthma that was well controlled. All had known food allergies, but had unknowingly ingested the foods responsible for the reactions. The reactions were to peanuts (four patients), nuts (six patients), eggs (one patient), and milk (two patients), all of which were contained in foods such as candy, cookies, and pastry. The six patients who died had symptoms within 3 to 30 minutes of the ingestion of the allergen, but only two received epinephrine in the first hour. All the patients who survived had symptoms within 5 minutes of allergen ingestion, and all but one received epinephrine within 30 minutes. The course of anaphylaxis was rapidly progressive and uniphasic in seven patients; biphasic, with a relatively symptom-free interval in three; and protracted in three, requiring intubation for 3 to 21 days. CONCLUSIONS: Dangerous anaphylactic reactions to food occur in children and adolescents. The failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome. PMID- 1294077 TI - Radiation protection associated with well women breast cancer screening. PMID- 1294078 TI - Further studies on the use of 2,2,2-trichloroethyl groups for phosphate protection in phosphoserine peptide synthesis. AB - Boc-Ser(PO3Tc2)-OH, Z-Ser(PO3Tc2)-OH and Fmoc-Ser(PO3Tc2)-OH, derivatives useful for peptide synthesis, have been obtained in high yields by acylation of H Ser(PO3Tc2)-OH.CF3COOH. The latter was obtained from Boc- or Z-Ser(PO3Tc2)-OBzl by simultaneous removal of the amino- and carboxy-protecting groups by Pd catalyzed hydrogenolysis in acetic acid-trifluoroacetic acid solution. Removal of the Tc-protecting group was efficiently achieved by hydrogenolysis in aqueous ethanol. PMID- 1294079 TI - Gastrointestinal endoscopy: an accurate and safe primary diagnostic and therapeutic modality. AB - OBJECTIVE: To review the place of gastrointestinal endoscopy in the management of upper and lower gastrointestinal disorders. DATA SOURCES: We reviewed articles on endoscopy reported over two decades. A Medline search complementing our experience and knowledge of the literature was used to identify the articles. STUDY SELECTION: Papers were selected which focused on indications, comparison with radiology, including clinical outcome measures, and complications. One hundred papers, including those from radiology journals, were reviewed. DATA EXTRACTION: Results of studies are referenced as appropriate. DATA SYNTHESIS AND CONCLUSIONS: Endoscopy allows direct visualisation of the mucosa of the upper gastrointestinal tract, colon and terminal ileum. Subtleties of colour change, vascular pattern abnormalities and scarring are easily detected at endoscopy and are often of diagnostic importance. Endoscopy also provides access for tissue biopsy and allows a wide variety of therapeutic interventions. Traditionally barium studies have been the first step in the evaluation of many gastrointestinal symptoms and still retain cost advantages over endoscopy. However, endoscopy is frequently more sensitive and specific than barium studies. Costs associated with incorrect diagnoses may undermine the apparent cost benefits of barium studies. Advances in endoscopic design have allowed wider therapeutic options and increased safety. Gastrointestinal endoscopy should now be the first line of investigation where diagnostic precision is required or where therapeutic intervention is likely. PMID- 1294080 TI - Rare x rare. PMID- 1294081 TI - Day-to-day variation of blood glucose and insulin responses in NIDDM subjects after starch-rich meal. AB - OBJECTIVE: To study day-to-day variation of postprandial blood glucose and insulin increments in non-insulin-dependent diabetes mellitus (NIDDM) subjects and to analyze intra- and interperson variance of response. RESEARCH DESIGN AND METHODS: Ten NIDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied. The subjects ate three meals of 90 g of white bread, with 7 days between tests. RESULTS: Mean +/- SD areas under the blood glucose response curve (above basal) over a 3-h period were 557 +/- 60, 569 +/- 74, and 565 +/- 67 mM x 180 min (NS), and areas under the insulin-response curve were 3350 +/- 448, 2815 +/- 359 and 3551 +/- 679 mU/L x 180 min (NS) on each of the three occasions. The 95% confidence intervals of blood glucose and insulin areas for the test meal repeated three times were 564 +/- 120 mM x 180 min and 3240 +/- 1645 mU/L x 180 min, respectively. Intra- and interperson components of variance were 25 vs. 75% (glucose) and 78 vs. 22% (insulin) of the total variance. The intraperson components of variance included all sources of variation other than between-person variation. There was no significant correlation between blood glucose and insulin response areas. CONCLUSIONS: A valid estimate of the glycemic response in a single patient is obtained after a single meal. Because of the large between-person variation, paired data should preferably be used when comparing glycemic responses to different foods. PMID- 1294082 TI - Preventing violence through primary care intervention. AB - Homicide was the United States' second leading cause of death among people aged 15 to 24 in 1988; non-fatal assaults occur 100 times more frequently. Yet as a society, we have ignored the problem. Risk factors for violent injuries comprise sociological, developmental/psychological and neurophysiological elements. Providers of primary care for children, young adults and their families can help parents develop healthy parenting techniques in child-rearing, help the grade school-aged child develop non-violent conflict-resolution skills, and help young people learn to avoid violence and potentially violent activities and situations. Health care providers are able to reduce the incidence of violent injuries by addressing the issue of violence in periodic examination visits with both parents and children. Familiarity with risk indicators enables the health care provider to intervene early when needed. An anticipatory guidance outline and a violence induced injury-visit form are included. PMID- 1294083 TI - Tissue expansion: its cost factor. PMID- 1294084 TI - Youth and tobacco: addiction and death. AB - Tobacco use by youth is a serious problem that can be handled by the combined attention of parents, youth advocates, health professional and youths themselves. Tobacco related addictions kill over 2,000,000 people worldwide every year and over 8,000 people in North Carolina. The best way to end such killings is to focus on prevention. Adolescents themselves can become leading advocates for a smokefree society and a healthier North Carolina for all of us. PMID- 1294085 TI - Clinical performance of ceramic brackets: a survey of British orthodontists' experience. AB - Eight-hundred-and-twenty-two British orthodontists were sent questionnaires regarding their use of ceramic brackets. Five-hundred-and-forty-six (66 per cent) responded, and from these, 512 (62 per cent) were analysed. Approximately half of these operators had experience with ceramic brackets, but only 32 operators had treated more than 30 patients. Clinicians' experiences and problems during treatment and debonding are discussed. PMID- 1294086 TI - Human insulin and hypoglycaemia: burning issue or hot air? PMID- 1294087 TI - Osteogenesis imperfecta: fractures of the femur when testing for congenital dislocation of the hip. PMID- 1294088 TI - Unexplained death in fit young people. PMID- 1294089 TI - Developing a district diabetic register. AB - OBJECTIVES: To compile a district wide diabetic register of all diabetic patients registered with general practitioners in the catchment area of a single district general hospital and to compare different approaches to identifying patients. DESIGN: Information for a register was obtained from general practitioners' practice registers, the Prescription Pricing Authority, and hospital diabetic clinic records. SETTING: Catchment area of an inner London district general hospital with a large diabetic clinic. SUBJECTS: All patients with a diagnosis of diabetes resident in or attending general practitioners or hospital clinics in the district or its catchment area. MAIN OUTCOME MEASURES: Prevalence of diabetes, population of patients elicited by different approaches, proportion attending the local district general hospital, cost of using prescription returns for identifying diabetic patients. RESULTS: 4674 patients with diabetes were identified from all sources of information, which corresponds to a mean of 22.4 patients per general practitioner and the prevalence of known diabetes of 1.17%. 39.4% of patients identified had Prescription Pricing Authority returns and 42.8% of patients appeared on practices' diabetic registers. Only 56.5% of patients identified attended the district general hospital. For practices where all sources of information were available, practice registers included 60.4% of all patients, and prescription returns and the clinic register identified 64.9% and 40.6% respectively. The cost of using prescription returns to identify patients not detected in other ways was 6.37 pounds per patient. CONCLUSION: The task of developing district diabetic registers may prove, even in one cross sectional attempt, a major task in many inner city health districts. PMID- 1294090 TI - So, what is a clinical oncologist? AB - The non-surgical management of patients with cancer often involves both radiation and medical oncologists. It is argued here that the term 'clinical oncologist' should encompass both specialties, but implicit in this is agreement in matters of both joint training and the delivery of treatment in integrated cancer centres. The provision of optimal care in district general hospitals as well as cancer centres also depends on a proper structure to which clinical oncologists provide the key. The newly created Joint Council on Oncology (involving representatives of the Royal Colleges of Physicians and Radiologists) should facilitate these agreements, breaking down old prejudices and helping to create a better standard of treatment for cancer patients in Britain. PMID- 1294091 TI - Damage to coaxial breathing systems. PMID- 1294092 TI - 'Acceptable' risk of drug treatment. PMID- 1294093 TI - Colposcopically directed punch biopsy: a potentially misleading investigation. PMID- 1294094 TI - Prenatal microbiological risk factors associated with preterm birth. PMID- 1294095 TI - Confined, managed and delivered: the language of obstetrics. PMID- 1294096 TI - Bile acid therapy for Helicobacter pylori. PMID- 1294097 TI - Comment: drug information centers in Europe. PMID- 1294098 TI - Very late immune response to growth hormone (GH) therapy in an infant with GH-N gene deletion. PMID- 1294099 TI - Controlling leprosy. PMID- 1294100 TI - Emergency feeding programmes. PMID- 1294101 TI - Misuse of temazepam. PMID- 1294102 TI - Reaccrediting general practice. PMID- 1294103 TI - Managing the persistent vegetative state. PMID- 1294104 TI - Exercising for health. PMID- 1294105 TI - Developing a district diabetes register. PMID- 1294107 TI - The meaning of insight. PMID- 1294106 TI - Indications for hyperbaric oxygen therapy. PMID- 1294108 TI - Re: The use of bladder pressure warning device during transurethral prostatic resection decreases absorption of irrigation fluid. PMID- 1294110 TI - Audit of general practitioner referrals to an acute surgical unit. PMID- 1294109 TI - Anterior resection without a defunctioning colostomy: questions of safety. PMID- 1294111 TI - Laparoscopic appendicectomy. PMID- 1294112 TI - Administrative blunders in Third World medicine. PMID- 1294114 TI - Monitoring nutritional status in burn patients. PMID- 1294113 TI - The quest for quality begins in medical school. PMID- 1294115 TI - Surgical correction of posttraumatic ventricular septal defect via the right atrium. PMID- 1294116 TI - Gunshot wounds to the heart. Utility of transesophageal echocardiography in assessment. PMID- 1294117 TI - Patient incidents. PMID- 1294118 TI - Organization of the gene encoding the human macrophage mannose receptor (MRC1). AB - The gene for the human macrophage mannose receptor (MRC1) has been characterized by isolation of clones covering the entire coding region. Sequence analysis reveals that the gene is divided into 30 exons. The first three exons encode the signal sequence, the NH2-terminal cysteine-rich domain, and the fibronectin type II repeat, while the final exon encodes the transmembrane anchor and the cytoplasmic tail. The intervening 26 exons encode the eight carbohydrate recognition domains and intervening spacer elements. However, no simple correlation between intron boundaries and functional carbohydrate-recognition domains is apparent. The pattern of intron positions as well as comparison of the sequences of the carbohydrate-recognition domains suggests that the duplication of these domains was an evolutionarily ancient event. PMID- 1294120 TI - Readers respond to nociceptive considerations. PMID- 1294119 TI - Isolation, mapping, and characterization of two cDNA clones expressed in the cerebellum. AB - In an effort to characterize genes expressed in the cerebellum, we have isolated two cDNA clones, H11B (D16S286) and 507 (D5S344), that hybridized to a cerebellar cDNA probe. Using a panel of human-rodent somatic cell hybrids, cDNA clone H11B was mapped to human chromosome 16, and clone 507 was mapped to human chromosome 5. TaqI RFLPs were identified with both clones and were used for linkage analysis in the CEPH families. D16S286 was tightly linked to several markers near chromosome 16p13, and D5S344 was tightly linked to several markers on chromosome 5q. Sequence tagged sites or expressed sequence tags were generated from the 3' untranslated regions of both cDNA clones. PMID- 1294121 TI - Intraosseous lipoma of the skull. PMID- 1294122 TI - Electrodiagnosis of botulism. PMID- 1294123 TI - Rheumatic mitral stenosis: balloon dilatation is not the alternative to closed mitral commissurotomy. PMID- 1294124 TI - Immunotherapeutic modification of Escherichia coli peritonitis and bacteremia by tinospora cordifolia. PMID- 1294125 TI - Diagonal earlobe creases: an association with primary open angle glaucoma. PMID- 1294126 TI - Epiphyseal migration of abnormalities in algodystrophy: the role of bone scintigraphy. PMID- 1294127 TI - Management of generalized faecal peritonitis. PMID- 1294128 TI - Pachydermoperiostosis mimicking acromegaly. PMID- 1294129 TI - Re: Renal transplantation in children with posterior urethral valves. PMID- 1294130 TI - Pain management for PEG? PMID- 1294131 TI - Thunderstorm associated epidemics of asthma. PMID- 1294132 TI - Predicting AIDS deaths and prevalence in Australia. PMID- 1294133 TI - The content of one doctor's practice. Resident training and the biopsychosocial model. PMID- 1294134 TI - National research projects and medical ethics. PMID- 1294135 TI - Angiotensin converting enzyme inhibitors for hypertension and heart failure? PMID- 1294136 TI - Misclassification among methods used for multiple group discrimination--the effects of distributional properties. PMID- 1294137 TI - Spinal abnormalities and the atypical form of the Mayer-Rokitansky-Kuster-Hauser syndrome. AB - In 96 patients with congenital absence of the uterus and upper vagina, the Mayer Rokitansky-Kuster-Hauser (MRKH) syndrome, it proved possible to distinguish between the typical and the atypical form using laparoscopy. The typical form was characterized by symmetrical nonfunctioning muscular buds (the Mullerian duct remnants) and normal fallopian tubes, and the atypical form by aplasia of one or both buds, one bud smaller than the contralateral one, with or without dysplasia of one or both fallopian tubes. The atypical form was found in 52 patients (54.2%). Radiographs of the spine showed that congenital spinal abnormalities, especially the Klippel-Feil (KF) syndrome, were seen in 14 of the 52 patients with the atypical form only. Renal agenesis or ectopia together with the MRKH and KF syndromes, known as the MURCS association (MU: Mullerian duct aplasia; R: renal agenesis/ectopia; CS: cervical somite dysplasia), was diagnosed in 10/52 patients in the atypical group. From our results we conclude that additional cervical spine films in patients with the MRKH syndrome are indicated only in the atypical form the syndrome. In those cases where the MRKH syndrome is associated with the KF syndrome, the MURCS association should be considered. PMID- 1294138 TI - Homoeopathic remedies. PMID- 1294139 TI - Docking of dogs: practical and ethical aspects. AB - Next month, the Council of the Royal College of Veterinary Surgeons will discuss the docking of dogs' tails, with a view to deciding whether docking for non therapeutic purposes should be considered as prima-facie evidence of disgraceful professional conduct. Here, Professor David Morton considers the arguments for and against tail docking, and the ethical issues involved. PMID- 1294140 TI - Taking chronic fatigue syndrome seriously. PMID- 1294141 TI - Taking chronic fatigue syndrome seriously. PMID- 1294142 TI - An ethnological approach to self-injurious behavior. PMID- 1294143 TI - Simplified quality of anaesthesia scoring system. PMID- 1294144 TI - Unexpected results: consider a medication error. PMID- 1294145 TI - Rehabilitation and outcome after severe head injury. PMID- 1294146 TI - Patterns of use of chest physiotherapy. PMID- 1294147 TI - Denture stomatitis. PMID- 1294148 TI - Safety of post-menopausal hormone replacement. PMID- 1294149 TI - Effect of bronchial smooth muscle contraction on lung volumes. PMID- 1294150 TI - Synthesis and clearance of atrial natriuretic factor in cirrhosis. PMID- 1294151 TI - Acquired immunodeficiency syndrome-related lymphoma. PMID- 1294152 TI - pH regulation in adult rat carotid body glomus cells. Importance of extracellular pH, sodium, and potassium. AB - The course of intracellular pH (pHi) was followed in superfused (36 degrees C) single glomus (type I) cells of the freshly dissociated adult rat carotid body. The cells had been loaded with the pH-sensitive fluorescent dye 2',7'-(2 carboxyethyl)-5 (and -6)-carboxyfluorescein. The high K(+)-nigericin method was used for calibration. The pHi of the glomus cell at pHo 7.40, without CO2, was 7.23 +/- 0.02 (n = 70); in 5% CO2/25 mM HCO3-, pHi was 7.18 +/- 0.08 (n = 9). The pHi was very sensitive to changes in pHo. Without CO2, delta pHi/delta pHo was 0.85 (pHo 6.20-8.00; 32 cells), while in CO2/HCO3- this ratio was 0.82 irrespective of whether pHo (6.80-7.40; 14 cells) was changed at constant PCO2 or at constant [HCO3-]o. The great pHi sensitivity of the glomus cell to pHo is matched only by that of the human red cell. An active Na+/H+ exchanger (apparent Km = 58 +/- 6 mM) is present in glomus cells: Na+ removal or addition of the amiloride derivative 5-(N,N-hexamethylene)-amiloride induced pHi to fall by as much as 0.9. The membrane of these cells also contains a K+/H+ exchanger. Raising [K+]o from 4.7 to 25, 50, or 140 mM reversibly raised pHi by 0.2, 0.3, and 0.6, respectively. Rb+ had no effect, but in corresponding concentrations of Tl+ alkalinization was much faster than in K+. Reducing [K+]o to 1.5 mM lowered pHi by 0.1. These pHi changes were shown not to be due to changes in membrane voltage, and were even more striking in the absence of Na+. Intrinsic buffering power (amount of strong base required to produce, in the nominal absence of CO2, a small pHi rise) increased from 3 to approximately 21 mM as pHi was lowered, but remained nearly unchanged below pHi 6.60. The fitted expression assumed the presence of one "equivalent" intracellular buffer (pK 6.41, 41 mM). The exceptional pHi sensitivity to pHo suggests that the pHi of the glomus cell is a link in the chemoreceptor's response to external acidity. PMID- 1294153 TI - [Sudden infant death. Should the definition be changed?]. PMID- 1294154 TI - [Pathologic anatomy in the monitoring of the liver transplant patient]. PMID- 1294155 TI - [Rabies encephalomyelitis with myocarditis and pancreatitis. Report on a case recently imported into France]. AB - We report the case of a 29 year-old man who died from rabies in France, following a dog-bite during a trip in Mexico. Although it was clinically suspected, the diagnosis was uncertain until he died because of digestive, cardiac and psychiatric misleading symptoms associated to the neurologic disorders. Post mortem diagnosis was based upon virological study in immunofluorescence on cerebral smears, viral isolation on cell-culture, and ELISA. It was confirmed by light microscopy examination which showed numerous Negri bodies, and ultrastructural study of the rhabdovirus in the central nervous system. Extranervous lesions, especially myocarditis and pancreatitis, were observed and their meaning is discussed. The physician is exceptionally confronted to the diagnosis of human rabies in France. Nevertheless, the lack of compulsory antirabic vaccination and the increase of touring in enzootic countries increase the risk of infection. As an intra vitam diagnosis in frequently lacking, the diagnosis of rabies infection needs a complete post mortem virological study as well as an histological and ultrastructural examination of the central nervous system. PMID- 1294156 TI - [Immunohistochemical demonstration of ceruloplasmin and lactoferrin in a series of 59 thyroid tumors]. AB - Fifty-nine thyroid tumors were re-examined and studied using immunohistochemistry to detect the presence of ceruloplasmin (CP), lactoferrin (LF), thyroglobulin, thyrocalcitonin, carcinoembryonic antigen and ferritin. In an attempt to study the contribution of the immunodetection of CP and LF in the diagnosis of malignant versus benign tumors, specially in follicular tumors, we compared our results of immunodetection with those of Tuccari and Barresi, and carried out our own studies on the usefulness of these immunolabelling. Concerning CP and LF staining, we have found the following data: 1) little (in contrast to Tuccari and Barresi) or no staining in normal thyroid and benign adenomas; 2) diffuse and intense staining in papillary and follicular carcinomas (as noted by the previous authors); 3) diffuse and weak staining for medullary carcinomas (in contrast to Tuccari and Barresi who found none). Our findings suggest that a diffuse and intense cytoplasmic staining with CP and LF concerning more than one third of all cells is a criterion of malignancy, whereas a weak paranuclear staining of a few cells is more in favor of a benign process. PMID- 1294157 TI - [Neuroendocrine carcinoma of the esophagus. Case report with immunohistochemical study]. AB - The authors report a case of neuroendocrine carcinoma of the lower third of the esophagus. Immunohistochemical study revealed that most tumor cells expressed neuron specific enolase, chromogranin A, carcinoembryonic antigen and glucagon. They insist on the usefulness of this study on biopsies in order to guide therapeutic decision. PMID- 1294158 TI - [Colonic elastoma. A pathologic study of 7 cases]. AB - The occurrence of elastic tissue abnormalities in the digestive tract is not common. There are sometimes observed in genetically transmitted connective tissue diseases in which numerous systemic complications are associated as in Ehlers Danlos and in Gronblad-Strandberg syndromes. We report 7 cases of an unusual lesion localized in the colon in which abnormally increased amounts of elastic tissue were observed. This elastosis raises many nosological and diagnostic difficulties. We propose the term "colonic elastoma" to describe this lesion. The review of the literature allows to consider several etiopathogenetic possibilities. PMID- 1294159 TI - [Cystic adenomatoid malformation of the lung, bilateral renal agenesis and left heart hypoplasia. An unusual association in Potter's syndrome]. AB - We describe an autopsy case of congenital cystic adenomatoid malformation of the lung (CCAM) associated with bilateral renal agenesis. Prenatal ultrasound examination showed additional left heart hypoplastic syndrome. A therapeutic abortion was induced at 23 weeks of gestation. The association CCAM-bilateral renal agenesis is a rare condition (5 cases previously described) which has to be known because of the mitigation effect of the CCAM on the oligohydramnios determined by bilateral renal agenesis. However, this instance is usually associated with oligohydramnios. The pathogenesis of polyhydramnios in isolated CCAM is discussed in regard with these data. PMID- 1294160 TI - [Axillary adenopathy indicating a tumor of the finger]. PMID- 1294161 TI - [Classification of tumors of the esophagus and stomach (OMS, 1990). Part I: Tumors of the esophagus]. PMID- 1294162 TI - [Follicular Hurthle cell tumors of the thyroid gland]. PMID- 1294163 TI - [A deceptive liver tumor: inflammatory pseudotumor. Report of a case]. PMID- 1294165 TI - Synthesis of modified prostaglandins and their inhibitory activity on natural killer cells. PMID- 1294164 TI - Synthesis and anti-inflammatory activity of 2-pyridyl-2-thiobenzothiazole derivatives. AB - A series of novel 2-pyridyl-2-thiobenzothiazole compounds was prepared and investigated by a number of in vitro methods in order to determine their anti inflammatory properties. Results are discussed with reference to well known NSAIDs. (3-carboxy-2-pyridyl)-2-thiobenzothiazole had the most potent anti inflammatory activity, being 1.34 times more active than indomethacin used as reference compound. PMID- 1294166 TI - 4H-thieno[3,4-c]pyrazole derivatives with antiinflammatory, analgesic, antipyretic and platelet antiaggregating activities. AB - The synthesis of a series of 1-aryl-1,6-dihydro-4H-thieno[3,4-c]pyrazol-4-ones by cyclization of 3-[(2-arylhydrazino)methylene]thiophene-2,4(3H,5H)-diones, prepared by reacting 3-dimethylaminomethylenethiophene-2,4(3H,5H)-dione with arylhydrazines, is described. The 4-fluorophenyl derivative showed remarkable analgesic, antiinflammatory and antipyretic activities in mice or rats, as well as a platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid. PMID- 1294167 TI - 2-substituted 1H-pyrrolo [3,2-h] quinoline derivatives: synthesis and aspects of their biological activity. AB - Certain 2-substituted 1H-pyrrolo [3,2-h] quinolines have been prepared and their biological activity in mammalian cells and in some microorganisms have been studied. These compounds represent a simplified ellipticine heterocyclic moiety: in addition they have a different ring condensation, leading to an angular molecular structure instead of a linear one. In mammalian cells all compounds appeared to be able of inducing an antiproliferative effect and an extensive DNA fragmentation, similarly to ellipticine, even if to a reduced extent. The new derivatives behaved in a comparable way also on some microorganisms, such as T2 bacteriophage (which appears to be less sensitive than mammalian cells) and in mutagenesis tests carried out with E. coli WP2 TM9 and S. typhimurium TA 98, which are reverted by base substitution and frame-shift mutagens, respectively. Similarly to the reference compound, all ellipticine analogues appeared to be no mutagenic. The obtained results suggest that they induce the antiproliferative activity in mammalian cells mainly as topoisomerase inhibitors, similarly to ellipticine itself. Therefore, they represent an interesting model to design new potential anticancer drugs. PMID- 1294168 TI - Photobiological activity of certain new methylazapsoralens. AB - The photobiological activity of a series of psoralen isosters carrying a nitrogen atom at 8 position, new potential drugs for the photochemotherapy of hyperproliferative skin diseases, have been studied; the more active derivatives appeared to be 5,4'-dimethyl-8-azapsoralen and 3,4,4'-trimethyl-8-azapsoralen which induced a strong inhibition of DNA synthesis in Ehrlich ascites cells, very similar to that provoked by 8-methoxypsoralen, the furocoumarin at present used in photochemotherapy. Such compounds induced a small amount of inter-strand DNA cross-links and were non phototoxic when assayed on guinea-pig skin; however, both derivatives appeared to be highly mutagenic in E. coli WP2 TM6. This strain contains the plasmid R46 and it is proficient in DNA repair, and therefore monoadducts do not should be mutagenic in such a strain. Because the first steps of excision, which remove monoadducts, and of the main cross-link repair use the same enzymes (produced by the uvrABC complex), in the presence of a great number of monofunctional lesions, it is possible that there are not sufficient enzyme molecules for removing cross-links according this pathway, which could be repaired by a second one, uvrABC independent and based on glycosilase activity, which works at reduced levels and is much less accurate. PMID- 1294169 TI - Antifungal and antibacterial activity of 2-acetylpyridine-(4 phenylthiosemicarbazone) and its metal (II) complexes. AB - 2-Acetylpyridine-(4-phenylthiosemicarbazone) and its metal (II) complexes have been synthesized and characterized by chemical and spectral methods. They were studied for their antibacterial and antifungal activities in vitro. The ligand and its metal (II) complexes exibited significant activity against a wide spectrum of bacteria and fungi. PMID- 1294170 TI - 3-Diazopyrroles. Part 5 (1). Antibacterial activity of 3-diazo-2-phenylpyrroles. AB - 3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c. The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity. PMID- 1294171 TI - Determination of sodium cromoglycate in pharmaceutical dosage forms using TLC densitometry. AB - A TLC-UV densitometric method for the determination of sodium cromoglycate (SCG) in ophthalmic solutions, gels and capsules has been developed. After TLC separation of active substance on silica gel GF254 using methanol-water ethylacetate (15:45:40 v/v/v) as the mobile phase, densitometric measurements were performed with HPTLC scanner at 254 nm. The proposed method is rapid and simple, free from interference by adjuvants and can be suggested for the routine analysis of sodium cromoglycate. PMID- 1294172 TI - [Textual study of Chinese drug loulu]. AB - Through a critical study of Loulu in ancient Chinese herbals, it is concluded that the botanical origin of Loulu should be Qizhou Loulu, the dried root of Rhaponticum uniflorum of family Compositae, while the dried root of Echinops latifolius, which is also one of the species specified in Chinese Pharmacopoeia, should not be used as Loulu because of its deficiency of herbal evidences and totally different chemical constituents from those of the former. It is therefore recommended the latter plant be deleted from the Chinese Pharmacopoeia. PMID- 1294173 TI - [Pharmacognostical studies on two species of Chinese drug caowu produced in Sichuan]. AB - This paper deals with 2 species of medicinal roots of Aconitum legendrei and A. geniculatum which are used in Sichuan as Caowu. The morphological and histological characteristics of these two roots are described. PMID- 1294174 TI - [Experimental studies on growing seedlings of Morinda officinalis How]. AB - By using the techniques of growing seedlings in bowshaped shed covered with plastic sheeting plus treatment with plant growth regulator, vegetative and generative propagation tests have been made of Morinda officinalis. Scientific evidences have thus been provided for growing seedlings of Morinda officinalis. PMID- 1294175 TI - [Effect of the root of Polygonum multiflorum Thunb. and its processed products on fat accumulation in the liver of mice]. AB - Experiments have shown that the root of Polygonum multiflorum exhibits inhibitory effect on triglyceride (TG) accumulation in the liver of mice induced by CCl4, cortisone acetate and thioacetamide (TAA). Its processed products (I, II) were found to be effective in lowering the accumulated TG induced by cortisone acetate. The root of Polygonum multiflorum and its processed products also reduced the enlargement of liver by CCl4. PMID- 1294176 TI - [Synchronized control of specific gravity, drug contents and recovery rate of inspissated extracts]. AB - As a result of experimentation we have developed a method that helps to synchronize the control of the three preset criteria, i.e. specific gravity, drug contents and recovery rate, in the process of preparing traditional Chinese medicines. Simple and easy to use, the method is also good for similar purposes in the preparation of traditional Chinese syrups. PMID- 1294177 TI - [Research on sterilization of pathogens by high electrostatic voltage method]. AB - An experimental research has been carried out on the sterilization of four kinds of pathogens by high electrostatic method along with an inquiry into the influence of voltage waveform and the treated time on sterilization. It is concluded that pathogens can be killed efficiently by corona discharge field. PMID- 1294178 TI - [Saponins in the fruit pedicels of Panax notoginseng (Burk.) F.H. Chen (continue)]. AB - Six saponins were isolated from the fruit pedicels of Panax notoginseng. Five of them were identified as gypenoside-XVII, -XV, ginsenoside-Rb1, and notoginsenoside-Fc, -Fa on the basis of chemical methods, spectroscopic analysis and comparison with authentic standards. Quantitative determination of the major saponins in fruit pedicels from the plant was made by thin layer chromatography densitometry. PMID- 1294179 TI - [Chemical constituents of Bauhinia hupehara Craib]. PMID- 1294180 TI - [Chemical constituents of Hedysarum polybotrys Hand.-Mazz]. AB - Butanedioic acid was isolated from the ethyl alcohol extract of Hedysarum polybotrys. The methylated carboxylic acid was identified by GC-MS method. PMID- 1294181 TI - [Anti-inflammatory and analgesic actions of artificial and fermentative Ganoderma sinense (AFGS)]. AB - Both AFGS and natural Ganoderma sinense (NGS) have obvious anti-inflammatory and analgesic effects for arthritis in rats induced by carrageenan and the pain reaction in mice induced by hot scalding as well as HAC-induced writhing. AFGS also can reduce the edematous swelling of mice's ears, reduce the capillary permeability of mice skin and obviously inhibit cotton pellets granuloma implanted in rats. It can promote cytophagy capacity of the reticular endothelial cells in mice. No irritation on the gastric mucosa in rats has been observed. PMID- 1294182 TI - [Pharmacokinetics of liensinine in rabbits]. AB - A method for the determination of plasma concentration of liensinine with HPLC and pharmacokinetic study of liensinine in rabbits were reported. Assay linearity was shown over the range of 0.125-2.5 micrograms/ml serum with regression coefficient of 0.9997. The mean recoveries of liensinine in plasma (within-day and between-days) were all more than 99% of the dose and the coefficients of variation were less than 5%. After a single intravenous injection of liensinine 6mg/kg to rabbit. The pharmacokinetic characteristics were found to fit a two compartment open model. Important parameters were: t1/2 alpha = 8.303 min t1/2 beta = 129.960min AUC = 132.67 micrograms.min/ml CL = 0.045 L/min Vc = 2.768 L/kg. PMID- 1294183 TI - [The protective effect of Hippophae rhamnoides L. on hyperlipidemic serum cultured smooth muscle cells in vitro]. AB - The effect of Hippophae rhamnoides on hyperlipidemic rabbit serum (HRS) cultured smooth muscle cells (SMC) was observed in comparison with vitamin E(VE). The results show that Hippophae rhamnoides, much like VE, is also a potent antioxidant. It strongly decreases the MDA content in HRS cultured SMC and protect the cells from the injury of lipid peroxidation, and thus keeps the SMC growing and proliferating health. The results implicate that Hippophae rhamnoides is an effective antioxidant, and one of the important mechanisms of Hippophae rhamnoides in anti-atherosclerosis reported recently may be closely related to the action of anti-lipid peroxidation. PMID- 1294184 TI - [A review on the synthesis of alkaloidal constituents of Chinese medicinal herbs in recent years in China]. PMID- 1294185 TI - Furan and thiophene analogues of omeprazole. AB - Synthesis and structure of some analogs of the omeprazole containing furan and thiophene rings are reported. Their effects on the basal and the histamine stimulated secretion were evaluated on the isolated rat stomach. PMID- 1294186 TI - Chemical stability of insulin. 4. Mechanisms and kinetics of chemical transformations in pharmaceutical formulation. AB - Insulin decomposes by a multitude of chemical reactions [1-3]. It deamidates at two different residues by entirely different mechanisms. In acid, deamidation at AsnA21 is intramolecularly catalyzed by the protonated C-terminal, whereas above pH 6 an intermediate imide formation at residue AsnB3 leads to isoAsp and Asp derivatives. The imide formation requires a large rotation around the alpha carbon/peptide carbonyl carbon bond at B3, corresponding to a 10 A movement of the B-chain N-terminal. The main determinant for the rate of B3 deamidation, as well as for the ratio between the two products formed, is the local conformational structure, which is highly influenced by various excipients and the physical state of the insulin. An amazing thermolysin-like, autoproteolytic cleavage of the A-chain takes place in rhombohedral insulin crystals, mediated by a concerted catalytic action by several, inter-hexameric functional groups and Zn2+. Intermolecular, covalent cross-linking of insulin molecules occurs via several mechanisms. The most prominent type of mechanism is aminolysis by the N terminals, leading to isopeptide linkages with the A-chain side-chain amides of residues GlnA15, AsnA18 and AsnA21. The same type of reaction also leads to covalent cross-linking of the N-terminal in protamine with insulin. Disulfide exchange reactions, initiated by lysis of the A7-B7 disulfide bridge, lead mainly to formation of covalent oligo- and polymers. Activation energy (Ea) for the neutral deamidation and the aminolysis reactions was found to be 80 and 119 KJ/mol, respectively. PMID- 1294187 TI - Chemical stability of insulin. 5. Isolation, characterization and identification of insulin transformation products. AB - During storage of insulin formulated for therapy, minor amounts of various degradation and covalent di- and polymerization products are formed [1-3]. The main chemical transformation products were isolated from aged preparations and characterized chemically and biologically. The most prominent products formed in neutral medium were identified as a mixture of deamidation products hydrolyzed at residue B3, namely isoAsp B3 and Asp B3 derivatives. A hydrolysis product formed only in crystals of insulin zinc suspensions containing a surplus of zinc ions in the supernatant was identified as an A8-A9 cleavage product. The small amounts of covalent insulin dimers (CID) formed in all formulations were shown to be a heterogenous mixture of 5-6 different CIDs with a composition dependent on the pharmaceutical formulation. The chemical characteristics of the CIDs indicate that they are formed through a transamidation reaction mainly between the B-chain N-terminal and one of the four amide side-chains of the A chain. GlnA15, AsnA18 and, in particular, AsnA21 participate in the formation of such isopeptide links between two insulin molecules. The covalent insulin-protamine products (CIPP) formed during storage of NPH preparations presumably originate from a similar reaction between the protamine N-terminal with an amide in insulin. Covalent polymerization products, mainly formed during storage of amorphously suspended insulin at higher temperature, were shown to be due to disulfide interactions. Biological in vivo potencies relative to native insulin were less than 2% for the split-(A8-A9)-product and for the covalent disulfide exchange polymers, 4% for the CIPP, approximately 15% for the CIDs, whereas the B3 derivatives exhibited full potency. Rabbit immunization experiments revealed that none of the insulin transformation products had significantly increased immunogenicity in rabbits. PMID- 1294188 TI - Relative bioavailability in man of noscapine administered in lozenges and mixture. AB - The bioavailability of noscapine base administered in lozenges in a dose of 100 mg to twelve healthy volunteers, in a study using an open balanced cross-over design, was compared with that of 100 mg of noscapine hydrochloride given perorally as a mixture. The bioavailability of noscapine after administration in lozenges was significantly higher than that after administration of the drug as a mixture. It is concluded that the lozenges containing noscapine base may be a valuable alternative to the conventional noscapine hydrochloride mixture. PMID- 1294189 TI - Bioactive compounds from nature. PMID- 1294190 TI - The limbic system: a review of its empirical foundation. AB - The concept of the limbic system is highly influential in many areas of the neurosciences and in their applications to clinical medicine. The value of this concept has been questioned, denied, and defended several times in the past but a comprehensive critical evaluation has never been published. In this article we take several approaches to analyse empirical data of relevance to the limbic system. First we delineate its factual application in different areas. The limbic system has a very wide scope and divergent use. Secondly we extract criteria for its definition from research literature using the bibliographic database Medline. The limbic system has been defined variously on a number of different descriptive levels from morphology to behaviour. Thirdly we review its empirical foundations comparing evidence from different sources. The limbic system lacks an adequate empirical definition in spite of numerous efforts. Last we evaluate its construction as a scientific concept from empirical facts. The limbic system is a non-empirical explanatory concept for poorly understood brain functions. We conclude that the concept of the limbic system cannot be accepted on empirical grounds. However, it is a very attractive concept in the search for explanation of brain function. The non-empirical contents of the limbic system remains largely unexplored. PMID- 1294191 TI - A fuzzy limbic system. PMID- 1294192 TI - Can rats solve a simple version of the traveling salesman problem? AB - Whereas correct tours through the radial arm maze are almost equally long, free choice mazes with multiple goals scattered in an open field allow the animal to select the shortest one from a multitude of correct tours. Thirteen rats were trained (at 10 trials per day) to visit an array of cylindrical feeders in an open field (40 x 100 cm) with reward available only when visiting the last feeder of the set. In Expt. 1 with eight feeders arranged in five different configurations the rats made after 10 days of training 1 error in the first 8 choices and incidence of errorless trials was about 20%. In Expt. 2. the use of six feeders in a rectangular (A) or double triangle (B) configuration increased the incidence of errorless trials to 60%. Expt. 3 showed that performance in the 6-feeder maze was significantly impaired by 6 mg/kg ketamine or 0.25 mg/kg scopolamine but not by lower dosages of these drugs. Tours generated on errorless trials (each feeder visited only once) during 10 days of Expt. 2 were analyzed. Six places can be visited in 6! = 720 different closed tours the lengths of which (in arbitrary units) range from 6.00 to 10.12 for A and from 6.83 to 10.47 for B. Whereas random generation of correct routes yielded only 5% of the shortest tours, they were clearly preferred by rats (41% in A and 45% in B). The apparent proficiency of rats in this optimization problem is probably not due to cognitive comparison of the possible correct routes but rather to following a simple rule 'Always go to the nearest not yet visited feeder'. PMID- 1294193 TI - The ontogenesis of sensorimotor reflexes in the Mongolian gerbil Meriones unguiculatus. AB - The ontogeny of a number of sensorimotor reflexes has been studied in the Mongolian gerbil. In contrast to a number of other mammals, the gerbil has relatively long and strong hindlimbs but small forelimbs, indicating their different importance for a number of locomotor acts, and during the developmental period studied, the hindlimbs grow at a much faster rate than the forelimbs. The following sequence of appearance and maturation of the reflexes was observed: rooting, forelimb hopping, surface body righting, forelimb grasp, hindlimb hopping, chin tactile placing, visual placing, air body righting and, at the same time, forelimb and hindlimb tactile placing. This sequence concords with the general gradient of development and maturation of the spinal and brain centers subserving these reflexes, as evaluated from Nissl preparations. The results indicate that there is no clearcut rostro-caudal gradient of postnatal maturation of the spinal cord and the spinally mediated reflexes, but that there is a general caudo-rostral gradient of brain maturation and of the brain-mediated reflexes. Comparisons with other mammals are made. PMID- 1294194 TI - Behavior-related cortical activity and swim-to-platform performance in the aged rat. AB - Aged rats (26 months) usually retained normal acetylcholine-dependent and serotonin-dependent forms of neocortical low-voltage fast activity and serotonin dependent hippocampal rhythmical slow-wave activity. In a simple swim-to-platform test, aged rats (23 and 26 months) performed normally in acquisition and in retention over a 7-day period. The results are discussed in relation to the common assumption that aged rats provide a valid model of human senile dementia. PMID- 1294195 TI - Classical conditioning after temporal lobe lesions in man: sparing of simple discrimination and extinction. AB - Recent reports of impaired conditional discrimination learning in temporal lobectomy subjects have raised the question of response inhibition deficits in these patients. In the present study, left and right temporal lobectomy subjects and healthy controls completed an eyelid conditioning task, which required simple two-tone discrimination learning, followed by extinction. There were no group differences with regard to discrimination learning or extinction. General deficits in response inhibition are therefore not likely to account for the impairment in conditional discrimination observed in temporal lobectomy patients. PMID- 1294196 TI - The effect of imagery perspectives on the psychophysiological responses to imagined exercise. AB - The effect of imagery perspectives, i.e. internal imagery vs. external imagery, on the psychophysiological responses to imagined exercise was investigated in the present study. Thirty male and female college students were randomly assigned to perform either internal imagery, external imagery or simple rest in addition to actual exercise. Metabolic, cardiovascular and perceptual responses were recorded before, during and after imagined exercise, actual exercise and rest. The results indicated that internal imagery resulted in a significant increase in ventilation and this response differed from the control condition. Effort sense was higher with internal imagery compared with external imagery. However, both internal and external imagery produced significant elevations in systolic blood pressure (SBP) from pre- to post-imagery, and these values were identical to those observed with actual exercise. Therefore, some responses to imagery were like those seen during actual exercise. Oxygen consumption (VO2), respiratory rate (RR), respiratory exchange ratio (RER), heart rate (HR) and diastolic blood pressure (DBP) were similar between internal and external imagery. It is concluded that the psychophysiological responses to internal imagery resemble actual exercise more than external imagery. PMID- 1294197 TI - Sexual behavior enhances postictal behavioral depression in kindled rats: opioid involvement. AB - Past research has demonstrated brain opioid and GABA release in response to ejaculation. In the present study we evaluated the potential role of these neurotransmitters in the postictal behavioral depression (PBD), after-discharge (AD) duration, and seizure intensity in rats kindled in the medial preoptic area (MPOA) and amygdala (AMG). The PBD, the AD duration and the seizure intensity were measured after a standard kindling stimulus and after a standard kindling stimulus applied 2 min after ejaculation. The PBD was significantly increased when the animals were stimulated 2 min after ejaculation. This increase was found in MPOA- but not in AMG-kindled rats. Ejaculation had no effect on AD duration or seizure intensity. Naloxone administration before the initiation of sexual behavior completely blocked the increase in PBD in MPOA-kindled rats. It is suggested, by indirect evidence, that opioid release during sexual behavior is added to the release associated with kindled seizures, increasing the duration of the PBD. Since sexual behavior lacked effect on AD duration or seizure intensity, no evidence could be found suggesting that functionally relevant amounts of GABA are released during this behavior. PMID- 1294198 TI - The function relating the subjective magnitude of brain stimulation reward to stimulation strength varies with site of stimulation. AB - A two-lever choice paradigm with concurrent variable interval schedules of reward was used to measure the growth in the subjective magnitude of reward as a function of current, by finding the adjustment in the stimulating current required to offset a given difference in the rates at which two rewards were received. Increasing current by a factor of 2 increased subjective reward magnitude by a factor ranging from as little as 3 to as much as 4,000. This range was about as great between electrodes within one rat as between electrodes and rats. In the light of earlier findings regarding the equivalent effects of increments is current and pulse frequency, these large differences cannot readily be explained by differing fiber densities at the site of stimulation. It is suggested that the medial forebrain bundle terminates in more than one spatio temporal integration mechanism. The magnitude of the spatio-temporally integrated effect of a barrage of action potentials in the reward-relevant axons depends on which subset of reward-relevant axons is excited by the stimulation. PMID- 1294199 TI - [Morpho-functional considerations on the annulate lamellae of the human oocyte]. AB - Ovarian biopsy specimens from four girls in complete remission state of acute lymphoblastic leukemia, previously treated with antiblastic chemotherapy for about three years, were examined by means of electron microscopy. The normal morphology of residual follicles and, in particular, the observation that annulate lamellae were always present in oocytes of primordial and primary follicles, gave the chance to consider a possible functional role and to suggest a prognosis for future fertility. The similarities in structure to the nuclear envelope and the relation between annulate lamellae and other cellular organelles (especially endoplasmic reticulum and ribosomes) suggest that lamellae may be involved in the release, assembly or activation of stored development information. The annulate lamellae could prove to be an important organelle that participates in the regulation of gene expression. Therefore, the presence of annulate lamellae in oocytes of primordial and primary follicles may present the possibility of a normal development for these cells in which long-lived gene products are synthesized and transported to the cytoplasm for storage and use later in development. The above hypothesis, while leads to consider these patients at risk for low fertility and early menopause, does not consider them as definitely infertile. PMID- 1294200 TI - [Intramural ganglia of the human gallbladder: morphological and functional observations]. AB - The purpose of this study was the reinvestigation of the intrinsic innervation of human gall bladder with an immunohistochemical technique named peroxidase anti peroxidase (PAP). The antigen demonstrated was the S100 protein normally present in the surface of glial cells, Schwann cells and satellite cells in ganglia. The tissues used were taken from 20 human gall bladders, fixed after surgery. This technique is not specific to demonstrate adrenergic or cholinergic innervation but it reveals just myelinated fibers. The current study was undertaken in order to study the organization and the function of plexus of nerves and ganglia present in the wall of the gall bladder. The neck of the gall bladder was the region in which the higher number of nerve cells and nervous fibers was present. The technique used has demonstrated ganglionated plexus and nerves in submucosal layer, fibromuscular and adventitial layer according to the enteric nervous system. All ganglia are postganglionic stations related with preganglionic cholinergic fibers. These results confirm that the intramural ganglia of the gall bladder are analogous to those of the enteric nervous system according to their common origin. PMID- 1294202 TI - Food ingestion and egestion in mating reactive populations of Paramecium primaurelia. AB - The study of food ingestion and egestion carried out on Paramecium primaurelia mating reactive cells shows that, after their transfer into a medium with suspended particles, the complementary mating type cells exhibit very significant differences in the food vacuole formation and egestion rate. Under the same external environmental conditions, the mating type II cells form and egest a higher number of food vacuoles when compared with mating type I cells. The higher rate of food vacuole formation shown by the mating type II cells is related to their faster growth rate. PMID- 1294201 TI - [Macronuclear DNA and total protein contents of mating types I and II of Paramecium primaurelia, during the phase of maturity and the transition to senescence. Preliminary observations]. AB - Concerning the studies on mating type differentiation and life cycle development in Paramecium primaurelia stock 90, both macronuclear DNA and total protein contents have been measured cytofluorometrically in mating type I and mating type II isogenic cell lines growing in logarithmic phase, throughout their maturity period and transition to senescence. The target was to investigate whether the two mating types undergo clonal decline in different times, as the previous studies suggested. The results indicate that, throughout the maturity period, macronuclear DNA and total protein contents vary both in mating type I and mating type II cell lines; moreover, aged phenotypes as the dramatic decrease of both contents, firstly occur in mating type II which, therefore, appears to be submitted to clonal decline before mating type I. PMID- 1294203 TI - [Mixed-function oxidase induction as a test for the biological monitoring of water: limitations and prospects]. AB - The induction in fish liver of some enzyme activities, and typically of microsomal mixed-function oxidases (MFO), provides the earliest biological warning signal of exposure to pollutants. Our studies provided evidence that the basal levels of cytochrome P-450 and specific MFO activities, such as arylhydrocarbon hydroxylase (AHH) and ethoxyresorufin deethylase (EROD), were strongly influenced by the diet in freshwater fish (Oncorhynchus mykiss). The response of fish liver to a known enzyme inducer, i.e., beta-naphthoflavone, was also affected by the diet, which therefore should be carefully controlled in laboratory studies. Under field conditions MFO activities were significantly enhanced in the liver of O. mykiss kept in polluted river water as well as in the liver of the seawater fish Diplodus annularis collected from a polluted harbour area, as compared to specimens of the same species collected from an unpolluted reference area. PMID- 1294204 TI - [Cytogenetic damage in fish (Oncorhynchus mykiss) exposed in situ to water from a polluted river]. AB - Specimens of rainbow trout (Oncorhynchus mykiss) were exposed in situ for 7, 15, and 30 days to the water of the Po River either upstream or downstream the immission of the Lambro River, a small affluent which is highly polluted with industrial wastes. A third group of animals was maintained as control in aquarium with a flow of unchlorinated fresh water. Blood smears were obtained from each of the 90 trout specimens and examined under the microscope. The number of micronucleated erythrocytes (MNE) was registered by scoring at least 2,000 cells per animal. No increases in the number of MNE was detected in the animals exposed upstream the confluence, as compared to controls. Conversely, a significant increase in the frequency of MNE after 7 days of exposure to the water of the downstream site was observed. This frequency remained elevated, yet not significantly, after 15 and 30 days of exposure. This study demonstrates the validity of in situ exposure and the usefulness of cytogenetic end-points for environmental biomonitoring. PMID- 1294205 TI - [Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 1) Studies during normal sodium and potassium balance]. AB - We have investigated the effective role of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in normal potassium balance in both absence (N3) and presence of E (N3.E). All subjects were submitted to normal dietary intake of sodium (150 mmol/d) and potassium (50 mmol/d). The basal values of PRA, urinary aldosterone and plasma electrolytes were in the normal range. The only significant effect produced by E was a reduction in mean arterial pressure, without significant changes in creatinine cl., urinary hydro-electrolyte excretions as well as urinary excretions of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294207 TI - [Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 3) Relative roles of angiotensin II and prostanoids in early hypokalemic dysfunction]. AB - We have investigated the relative roles of some renal prostanoids and angiotensin II in the hypokalemic renal dysfunction. To this aim we have evaluated the renal function in healthy women in induced potassium depletion of moderate degree before and after acute inhibition of cyclooxygenase (indomethacin, I) or angiotensin converting enzyme (enalapril, E). The renal function was explored by clearance (cl.) method during hypotonic polyuria induced by oral water load followed by 5% dextrose solution infusion; the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Potassium depletion was induced in 12 subjects by adaptation to low potassium (< or = 10 mmol/d) and normal sodium (150 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. In 6 subjects paired functional studies were performed in absence (D3) and presence of I (D3.I), 100 mg administered i.m. immediately before the water load. In other 6 subjects, paired studies were performed in absence (D4) and presence of E (D4.E), 10 mg administered per os 1 hour before the water load. No significant difference between D3 and D4 was observed as regards the potassium cumulative deficit as well as the basal values of plasma potassium concentration and plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294206 TI - [Renal effects of the acute inhibition of angiotensin-converting enzyme. I. 2) Studies during moderate potassium depletion]. AB - We have investigated the relative roles of angiotensin II on the renal function and urinary excretion of some prostanoids in healthy women submitted to different conditions of potassium balance. To this aim we have evaluated the effects of an acute inhibition of angiotensin converting enzyme by enalapril (E). The renal function was explored by clearance (cl.) method during induced hypotonic polyuria (oral water load followed by 5% dextrose solution infusion). During 60 min cl. period the urinary PGE2, 6-keto-PGF1 alpha and TxB2 were determined by RIA method. Each subject received paired studies, in absence and presence of E (10 mg administered per os 1 hour before the water load). Basal values of plasma renin activity (PRA) and urinary aldosterone (excreted during the 24 hours before the water load) were also determined by RIA method. This study protocol was applied in normal potassium balance (n = 6) and induced moderate potassium depletion (n = 6). This paper concerns the group in potassium depletion in both absence (D4) and presence of E (D4.E). Potassium depletion was induced by adaptation to a normal sodium (150 mmol/d) and low potassium (< or = 10 mmol/d) dietary intake combined to natriuretic treatment. The water and NaCl net losses were restored by 0.9% NaCl solution infusion. The cumulative potassium deficit achieved at the end of the depletive treatment was 214 +/- 54 mmol. This treatment induced significant decrease in basal plasma potassium concentration and increase in PRA without affecting urinary aldosterone and plasma sodium concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294208 TI - Reliability and upper normal variability limits of pattern reversal visual evoked potential parameters. AB - Twenty healthy volunteers aged 21-48 years (10 males, 10 females) were submitted to pattern reversal visual evoked potentials with 15' and 30' checks. The recordings were repeated after 7 days to assess reliability and upper normal variability limits of the following parameters: latencies of N70, P100, N140 and peak-to peak amplitudes of N70-P100, P100-N140. Reliability was tested with intraclass correlation coefficient, which was excellent or good for all parameters. Test-retest variability limits were computed with = 0.01 for absolute latency differences and relative amplitude differences. PMID- 1294210 TI - [We should get along without nurses]. PMID- 1294209 TI - Study of 4-NQO induced mutations at the HPRT locus in CHO cell lines. Possible influences of preferential DNA-repair on the mutational spectrum. AB - In the attempt to determine the possible influence of excision repair processes on 4-NQO mutational spectra in mammalian cells, 4-NQO-induced mutants at the hprt locus were isolated in excision repair proficient (AA8) and deficient (UV5) CHO cell lines. DNA sequencing data on these mutants revealed that DNA repair may indeed modulate the induced mutational spectrum. In particular, more splice mutations were found in the repair proficient than in the repair deficient cells. This can be interpreted by a difference in repairability of the two principal 4 NQO G-adducts or by the existence of a transcription-coupled DNA preferential repair process. PMID- 1294211 TI - [Safe with nurse-anesthetists. Interview by Bjorn Arild Ostby]. PMID- 1294212 TI - [Danish EEC-invitation]. PMID- 1294213 TI - [Hospitals for employees?. Interview by Bjorn Arild Ostby]. PMID- 1294214 TI - [Patients are not the clients. Interview by Bjorn Arild Ostby]. PMID- 1294215 TI - [No, to antibiotics regulation]. PMID- 1294216 TI - [Nursing under a different sky--India]. PMID- 1294217 TI - [Ecuador: lepers fear banishment from society. Interview by Segio Gaete]. PMID- 1294218 TI - [Observations by a pregnant nurse]. PMID- 1294219 TI - [Latvia--Norwegian Nurses' Association's new cooperative partner]. PMID- 1294220 TI - [New transfer technique for stroke patients]. PMID- 1294221 TI - [Occupational health nursing: environment on the agenda]. PMID- 1294222 TI - [Can nursing care replace drugs?]. PMID- 1294223 TI - [NSF (Norwegian Nurses' Association) guides KS (District Central Organization) in labor laws: guidelines are voluntary]. PMID- 1294224 TI - [Nursing with the swastika as guiding star. "Lost without ethics"]. PMID- 1294225 TI - [Nursing with the swastika as guiding star. Nothing is black or white. Interview by Bjorn Arild Ostby]. PMID- 1294227 TI - [Big ambitions on patients' behalf]. PMID- 1294226 TI - [New career opportunities for nurses in professional jobs]. PMID- 1294228 TI - [Labor laws: guidelines mean more work for nurses]. PMID- 1294229 TI - [Torture and imprisonment did not break Miriam Bergholz. Nursing and solidarity through Norwegian project in Cairo. Interview by Erling Bergan]. PMID- 1294230 TI - [Nursing under a different sky--Tanzania]. PMID- 1294231 TI - [Central America: alarming spread of disease blamed on water]. PMID- 1294232 TI - [Warning against shifts on request. Interview by Kjell Arne Bakke]. PMID- 1294233 TI - [Nursing with the swastika as guiding star]. PMID- 1294234 TI - [Nursing with the swastika as guiding star. Assigned by the Red Cross to work for the Germans. Interview by Kjell Arne Bakke]. PMID- 1294235 TI - Sex, race, age, and violent offending. AB - Although there is an increase in attention being paid to race and sex variations in crime and delinquency, little has been done to disaggregate the "gender-ratio" problem in order to account for participation in particular offenses, specifically different types of violent crime. Virtually all of the research pertaining to the interaction of gender, race and -violent crime focuses on murder and dichotomizes race into white and black, or white and nonwhite. This paper uses New York City arrest data to examine the extent of violence within various race-sex-crime subgroups. Rates of violent offending (i.e., homicide, robbery, assault, and burglary) are presented for black, Hispanic and white males and females. Regardless of violent crime type, black and Hispanic females exhibited high rates of offending relative to white females. Furthermore, the violent offending rates of black females paralleled those of white males. These findings suggest that an examination of gender differences in violent offending, independent of race, will produce incomplete and potentially misleading interpretations. The paper also provides a social structural explanation of the disproportionate involvement of black females (and males) in violent crime. PMID- 1294236 TI - Patterns of homicide among the elderly. AB - Forty-five homicide offenders aged 55 and older are analyzed in the contexts of their deadly acts. Analyses include demographic and social characteristics of offenders and victims, demographic and social relationships between offenders and victims, circumstances of offense, and arrest disposition. Where feasible, comparisons are made with age-general populations of homicide offenders. Explanatory insights based on the "routine activity approach are offered. PMID- 1294237 TI - Attitudes and practices of doctors toward spouse assault victims: an Australian study. AB - The attitudes and practices of 96 doctors toward spousal assault victims in the Australian Capital Territory, Australia, were investigated by questionnaire surveys distributed to general practitioners. The results indicate that although most doctors believe that members of their profession should play a role in prevention and treatment, many doctors may be failing to do so. In general, the sample was fairly homogeneous attitudinally, although long-serving practitioners tend to have more conservative attitudes about the causes of spousal assault and about doctors' role in prevention; and female doctors have more liberal beliefs than males about some aspects of causation and intervention. However, the latters' responses are less sympathetic when questioned about their own feelings and practices. Very few of the doctors had received any training on domestic violence issues, and for those that had, such training was minimal. There is nevertheless an indication that training has influenced some beliefs. The findings are not surprising in the context of the historical and current Australian ethos which perpetuates traditional gender stratification and wife battering. PMID- 1294238 TI - Coping capacity among women with abusive partners. AB - Coping capacity, although increasingly implicated as a mediating force in how individuals respond to personal threat, is an underrecognized factor in work with women of abusive partners. To explore the utility of coping capacity as a multivariable set to guide intervention with women of abusive partners, findings are reported comparing four groups of women: those whose partners do not engage in abuse, are abusive toward them, are sex offenders of children for whom the woman is a parent, or are offenders of children for whom the woman is not a parent. Three variable sets were included: vulnerability factors that may negatively influence appraisals of threat and ability to cope with abuse; coping responses that include cognitive, emotional, and behavioral reactions to the abuse; and coping resources expected to mediate effects of vulnerability factors and to influence the mobilization (of lack thereof) of coping responses. There were significant differences in coping capacity profiles across the four groups. These appeared to be a continuum of coping capacity, with women who were most directly threatened showing the lowest and women who were least directly threatened showing the highest levels of coping capacity. In order from the lowest to the highest levels of coping capacity were (1) battered women, (2) women whose partners are offenders against their children, (3) women whose partners are offenders against children of whom they are not the parent, and (4) control group women. The paper ends with a conceptual interpretation of the mediating functions of coping resources and implications for intervention and further study. PMID- 1294239 TI - The role of family factors, physical abuse, and sexual victimization experiences in high-risk youths' alcohol and other drug use and delinquency: a longitudinal model. AB - Our understanding of the adverse effects of early child physical and sexual abuse has developed to a point where there is need to elucidate the processes by which various developmental outcomes occur. Limited variability on key measures of family stress and in youths' drug use, other delinquent behavior and abuse histories in the general population has limited theory development. Using data from an ongoing, longitudinal study of juvenile detainees, we test a developmental damage model of the relationships among the youths' family background and problem factors, their sexual victimization and physical abuse experiences, and their substance use and delinquent behavior over time. The hypothesized model was supported by the data. Theoretical and policy implications of the results are drawn. In particular, early intervention with high-risk youths and their families is needed to address effectively their problems and troubled behavior before drug use and delinquent careers become firmly established. PMID- 1294240 TI - After the crisis: a needs assessment of women leaving a domestic violence shelter. AB - The current study presents the results of a needs assessment of 141 women exiting an emergency shelter for women with abusive partners. Extensive in-person interviews were conducted. Results indicate that battered women need numerous community resources upon their shelter exit, including legal assistance, employment, and housing. Race, age, and whether a woman was returning to her assailant influenced which resources she reported needing at shelter exit. Most of the women had experienced severe abuse and injuries, and required physical protection. Implications of these findings as they relate to program development and integration of social services are discussed. PMID- 1294241 TI - Mitochondria and aging: the universality of bioenergetic disease. PMID- 1294242 TI - The role of mitochondrial DNA rearrangements in aging and human diseases. AB - Instabilities and point mutations of the high molecular weight mitochondrial DNA (mtDNA) were shown to be correlated with various degenerative processes in both lower eukaryotes as well as in mammals. In filamentous fungi, circular and linear plasmids were demonstrated to be involved in mtDNA rearrangements and in the genetic control of senescence. In addition, in these eukaryotic microorganisms, which have proved to be ideal model systems in experimental gerontology, a number of nuclear genes were identified controlling the stability of the mitochondrial genome. Although the mitochondrial genome of mammals, including humans, appears to be quite stable in comparison to other species, mtDNA instabilities of the type described in fungi were observed in mitochondria of patients with different mitochondrial degenerative disorders (CPEO, KSS, Pearson syndrome, LHON, MERRF, MELAS). It was later demonstrated that such mtDNA rearrangements appear to accumulate progressively during aging in human subjects. These data suggest that instabilities of the mitochondrial genome may play an important role in the control of life span not only in lower eukaryotes, but also in humans. PMID- 1294243 TI - Coping with health problems in old age. A longitudinal approach. AB - An analysis of medical, psychological, and social data of the Bonn Longitudinal Study on Aging, comparing a subgroup of the BOLSA sample, which developed different forms of chronic disease four to six years after the beginning of the study, and a healthy subsample, points to different patterns of coping in these two subgroups. The sequence of these response patterns provides some evidence for a special form of psychosocial competence of chronically ill aged persons, which developed in an 'accelerated' way in the ill group, and in a retarded way in the initially healthy group. The findings emphasize the need for continuing research into the psychosocial aspects of coping with chronic disease in old age. PMID- 1294244 TI - The oldest old and their children: how strong are the relationships? AB - Eighty-five-year-old parents (N = 99) and their middle-aged children (N = 58) participated in a study on solidarity in intergenerational relationships in Sweden. The research model utilized evaluated six dimensions of family solidarity: family structures and associational, affectional, consensual, functional and normative solidarity. The finding of close family bonds in most of these areas may be attributed to the fact that the extensive Swedish public home help system facilitated relationships on more equal terms. While the children were relieved from much responsibility for their parents' needs, most parents did not experience feelings of dependency on their children. It was in fact evident that even very old parents can be a source for help to their children. Children were, however, the main providers for emotional support and this role could not be substituted by formal caregivers. PMID- 1294245 TI - Differences in cerebrospinal fluid gangliosides between "probable Alzheimer's disease" and normal aging. AB - The four major brain gangliosides, GM1, GD1a, GD1b, and GT1b, were determined in cerebrospinal fluid (CSF) of 43 patients with "probable Alzheimer's disease (AD)" and 40 healthy controls without psychiatric or neurological disorders. The total concentration of the four gangliosides did not differ significantly between "probable AD" group (116 +/- 58 nmol/L) and controls (92 +/- 31 nmol/L), but the proportion between the gangliosides was changed. In the "probable AD" group compared with the age-matched control group, there was an increase in both the GM1 (22.6 +/- 9.3% vs 12.6 +/- 4.1%; p < 0.0001) and GD1a (32.1 +/- 9.8% vs 23.3 +/- 5.7%; p < 0.0005) proportion, and a decrease in the GD1b (20.0 +/- 6.6% vs 23.8 +/- 6.0%; p < 0.05) and GT1b (25.3 +/- 7.9 vs 40.3 +/- 9.3%; p < 0.0001) proportion. The proportion of GM1 showed a positive correlation with age in the control group (r = 0.45; p < 0.01), but a negative correlation with age in the "probable AD" group (r = -0.37; p < 0.05). Thus, although the increase in proportion GM1 in the "probable AD" group was preferentially found in younger "probable AD" patients, it was not caused by age differences. While the pathogenetic mechanism for these changes in CSF-gangliosides in "probable AD" remains to be established, it may reflect the degeneration of nerve cells and synapses. PMID- 1294246 TI - Components of competence in the community aged. AB - Following a discussion of different approaches to the definition of 'competence' and their theoretical background, the need for both situation-specific and global conceptualizations of this construct is stressed. Aside from competencies for physical and social survival, those related to psychological survival should be considered. A battery of indicators of competence, as used in the Bonn Longitudinal Study on Aging (BOLSA), was helpful in identifying six groups of elderly people with different levels of competence in the range of 'normal' aging. Cognitive and personality variables most significantly differentiated the competence groups. On the basis of these findings, the value of complex competence models and the need for situation-specific and person-specific assessments of competence is stressed. PMID- 1294247 TI - Unrecognized dementia: sociodemographic correlates. AB - Eighteen geriatric patients, aged 77 +/- 8 years, in whom a diagnosis of dementia was formulated during an unrelated hospital stay, were studied to clarify why dementia had not been detected at an earlier stage. The control group was composed of 20 patients aged 79 +/- 11 years with a comparable degree of cognitive impairment who had been recognized 1-3 years previously. The index group was characterized by a lower formal education (5.2 +/- 3.7 years vs 8.5 +/- 4.7 years, p < 0.05), and higher prevalence of subjects living in rural areas (50% vs 10%, p < 0.006); other sociodemographic variables (age, sex, marital status, employment before retirement) could not distinguish the groups. A multivariate logistic regression analysis showed that the end point late diagnosis was significantly correlated with the independent variables, rural residence (odds ratio = 4.65, C.I. = 1.7-12.9) and lower occupational role (odds ratio = 3.3, C.I. = 1.2-9.5). A structured interview with relatives of the patients disclosed 3 main reasons accounting for later diagnosis: poor awareness of the problem of dementia; respect for parents and grandparents; and negligible effect of this problem on family life and economy. In the control group, dementia had been diagnosed earlier mostly because of its heavier social and economic impact on the family. PMID- 1294248 TI - Differentiated thyroid carcinoma in the elderly. AB - Prognostic factors and therapeutic results in a group of 268 patients with differentiated thyroid cancer (DTC) aged over 60 years are reported. These cases were selected from a total of 1457 DTC-patients seen at our Center from 1967 to 1987. All elderly patients underwent total thyroidectomy, and were treated with 131I therapy and suppressive hormonal therapy. Moreover, external radiotherapy was performed in 20% and chemotherapy in 3.8% of all cases. Follow-up included periodical clinical examination, serum Thyroglobulin (Tg) determination, 131I total body scan (TBS), and echographic and radiologic survey. Several unfavorable prognostic factors were identified in elderly patients with DTC. In comparison with data obtained in a group of patients under 60 years of age, 1) the follicular histologic type was increased, papillary/follicular ratio was 1.1 vs 2.6; 2) the F/M ratio was decreased, 1.5 vs 2.8 for papillary tumors, and 1.7 vs 3.6 for follicular tumors; 3) the rate of cases with local extrathyroid tumor growth and distant metastases was higher, and 4) rates of metastases to bone and metastases with low 131I uptake were increased. Moreover, the 10-year survival rate in elderly patients with lymph node and distant metastases was significantly reduced compared to younger patients, both for papillary and follicular cancer. The finding of detectable serum Tg levels was well correlated with the presence of metastatic disease. Moreover, Tg sensitivity was higher than TBS in showing the presence of metastatic foci. DTC in elderly people must be considered an aggressive tumor both for follicular and papillary histologic types. A radical approach is recommended: total thyroidectomy, 131I administration, and suppressive hormonal therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294249 TI - 80-year-old men have elevated plasma concentrations of catecholamines but decreased plasma renin activity and aldosterone as compared to young men. AB - Plasma concentrations of adrenaline, noradrenaline, aldosterone and plasma renin activity were determined in a selected group of 80-year-old men (N = 41) in good health without clinical signs of cardiovascular disease, and were compared to levels in young healthy males (N = 20, 24-28 years). Plasma adrenaline and noradrenaline concentrations were higher (0.24 median; 25th-75th percentiles 0.16 0.34 nmol/L vs 0.15; 0.11-0.18 nmol/L, p < 0.01 and 2.22; 1.58-3.27 nmol/L vs 1.15; 1.00-1.74 nmol/L, p < 0.001), and plasma renin activity and plasma aldosterone concentration were lower in the old than in the young men (0.65; 0.35 1.04 micrograms/L/1h vs 2.09; 1.23-2.41 micrograms/L/1h, p < 0.001 and 0.12; 0.09 0.19 nmol/L vs 0.38; 0.28-0.54 nmol/L, p < 0.001). In conclusion, increased plasma concentrations of catecholamines and decreased plasma concentration of aldosterone and plasma renin activity in old men, as compared to young men, must be considered when interpreting data of these hormones in elderly men. PMID- 1294250 TI - A comparison of community care of elderly people in Wales and Northern Ireland. AB - This study compares the provision of community services for elderly people in Wales and Northern Ireland using data from two independent surveys. Despite sampling and definitional problems, certain interesting comparisons can be obtained. In general, elderly people in the Northern Ireland sample seem more likely to be dependent and more disabled than those in Wales. Northern Ireland people receive less help, but the help given is more likely to be from statutory services than in Wales; in many cases statutory help is the sole source of support. Further, in Wales there is more specialized care for very disabled elderly people living in the community, and the work is more likely to be shared by carers and the statutory services. There is however still considerable unmet need in both countries. A comparative study using common definitions and methods would be of considerable interest in relation to the debate concerning the relative shares of health care resources in the United Kingdom. PMID- 1294251 TI - [Molecular and cellular aspects of the cardioprotective mechanism of phosphocreatine]. AB - The present state of investigations on molecular and cellular mechanisms of cardioprotective effects of phosphocreatine (PCr) is reviewed. The protective effect of PCr is manifested as significant improvement of heart contractile function recovery, lowering of diastolic pressure elevation and myocardial enzymes release during postischemic reperfusion as well as better preservation of high energy phosphates in comparison with control. Data from multidisciplinary studies using physico-chemical, physiological, pharmacological etc. approaches suggest that one of the key mechanisms of PCr action is its interaction with the sarcolemmal membrane. The authors own data obtained with the use of spin-labeled ESR-probe incorporated into the isolated sarcolemmal vesicles provide direct evidence in favor of the ordering effect of PCr sarcolemmal phospholipid packing with essential involvement of Ca2+ ions. PCr transform membrane phospholipids into more structured gel-like state. The results of biomedical studies suggest that the mechanism of this protective action is complex and includes at least four components: 1) inhibition of lysophosphoglyceride accumulation in the ischemic myocardium and preservation of cardiac cell sarcolemma structure via zwitterionic interaction with PCr molecules; ii) extracellular action consisting in inhibition of platelet aggregation via ADP removal in the extracellular creatine kinase reaction and increasing plasticity of red blood cells; iii) PCr penetration into cells maintenance of high local ATP levels is possible; iiii) inhibition of adenine nucleotide degradation at the step of 5'-nucleotidase reaction in cardiac cell sarcolemma. PMID- 1294252 TI - [Enzymes in thick filaments of vertebrate cross-striated muscles]. AB - Contemporary data on three enzymes of vertebrate cross-striated muscle thick filaments, such as creatine kinase, AMP-deaminase and phosphofructokinase, are reviewed. The physico-chemical, enzymatic and regulatory properties and localization of these enzymes in different zones of the thick filament are considered. The functional relevance of localization of creatine kinase, AMP deaminase and phosphofructokinase on thick filaments is discussed in terms of the possible role of the enzyme adsorption on subcellular structures in regulation of metabolic processes. PMID- 1294253 TI - [The effect of lysolecithin on rat liver microsome monooxygenase activity after induction by xenobiotics of the methylcholanthrene type]. AB - Effects of exogenous gamma-myristoyl- and gamma-palmitoyllysolecithins on physico chemical characteristics of rat liver microsomes, such as hydrophobicity and viscosity, as well as on oxidative NADPH-dependent O-deethylation of 7 ethoxycoumarin (7-EC), O-demethylation of p-nitroanisole (p-NA) and hydroxylation of 3.4-benz(a)pyrene (BP) induced by the mechylcholanthrene xenobiotics methylcholanthrene (MCh), beta-naphthoflavone (NF) and Sovol (SV) have been investigated. The specific inducible form of P-450c showed different affinity for the substrates. Lysolecithin decreased the hydrophobicity but only slightly increased membrane viscosity, whereas the monooxygenase substrates neutralized these effects. Lysolecithin (2-20 micrograms/mg of microsomal protein) inhibited the activity of deethylase 7-EC (maximally by 11%) in NF- and SV-induced microsomes, this inhibiting effect being more pronounced than that in MCh-induced microsomes. At higher concentrations lysolecithin inhibited the rate of 7-EC deethylation in MCh-induced microsomes more strongly; the maximal inhibition (23%) was observed at the protein concentration of 60 micrograms/mg. In case of NF- and SV-induced microsomes the inhibition was 18%. The inhibiting effect of lysolecithin on 7-EC dealkylation was expressed in a lesser degree than that on p NA O-demethylation in induced (but not intact) microsomes. A significant positive correlation has been found between the changes in hydrophobicity and inhibition rates in the presence of lysolecithin, however only for 7-EC deethylation. PMID- 1294254 TI - [Regulation of the activity of neuron-specific enolase by certain endogenous compounds]. AB - The effects of glycolysis metabolites and some amino acids on the activity of bovine brain enolase have been studied. The inhibiting effect of glycolysis metabolites, of which two (2-phosphoglycolate and glyceraldehyde 3-phosphate) may be functionally significant, has been demonstrated. The action mechanisms of these compounds within a range of physiological concentrations as well as the combined effect of glyceraldehyde 3-phosphate and phosphoglyceromutase on enolase activity have been investigated. PMID- 1294255 TI - [The effect of tetrahydrofuran on the microsomal monooxygenase system in vitro and in vivo]. AB - The effects of tetrahydrofuran (THF) on rat liver microsomes in vitro and in vivo were opposite. In vitro THF inhibited the p-nitrophenol (PNP) hydroxylase activity of microsomes from control rats and from rats treated with PB, acetone, and isoniazide--by 50, 20, 60, and 80%, respectively. THF inhibited dimethylnitrosamine (NDMA) demethylation in control and induced microsomes in a lesser degree. THF increased the total cytochrome P-450 content as well as the contents of cytochromes P-450IIE1 and P-450IIB1/B2. The activities of PNP hydroxylation and NDMA-demethylation increased also, whereas the PR-dealkylation activity was unchanged. An increase in the THF dose caused inhibition of the rat liver microsomal monooxygenase system. PMID- 1294256 TI - [Uneven distribution of amino acid substitutions throughout the amino acid sequence of homologous proteins]. AB - A set of aligned homologous protein sequences is divided into two groups consisting of m and n most related sequences. The value of position variability for homologous protein sequences is defined as a number of failures to coincide in the intergroup comparison of all possible m*n pairs of amino acid residues in that position divided by m*n. The position variability value plotted versus the sequence position number with a window of 10 positions gives the intergroup local variability profile. Area S of the figure included between the local variability profile and the straight line corresponding to the mean local variability value is compared with the average area Sr for 1000 random homologous protein families. If S is greater than Sr by more than 2 standard deviation units sigma r, the local variability profile is assumed to contain peaks and hollows corresponding to significant variable and conservative regions of the sequences. The profile extrema containing the area surplus delta S = S-(Sr+ 2 sigma r) are cut off by two straight lines to locate significant regions. The difference (S-Sr) given in standard deviation units sigma r is believed to be the amino acid substitution overall irregularity along the homologous protein sequences OI = (S-Sr)/sigma r. The significant conservative and variable regions of six homologous sequence families (phospholipase A2, cytochromes b, alpha-subunits of Na,K-ATPase, L- and M-subunits of photosynthetic bacteria photoreaction centre and human rhodopsins) were identified. It was shown that for artificial homologous protein sequences derived by k-fold lengthening of natural protein sequences, the OI value rises as square root of k. To compare the degree of substitution irregularity in homologous protein sequence families of different lengths L the value of standard substitution overall irregularity for L = 250 is proposed. PMID- 1294257 TI - [Purification and properties of pyrocatechase II from Pseudomonas putida strain 87]. AB - Induction of modified ortho-pathway enzymes (catechol 1.2-dioxygenase II, muconate cycloisomerase II, dienelactone hydrolase, and maleylacetate reductase) was found in Pseudomonas putida 87, when 3-chlorobenzoic acid was used as a sole carbon and energy source. Catechol 1.2-dioxygenase II, the key chlorocatechol cleaving enzyme, was purified and characterized. The enzyme molecular mass as determined by gel filtration was 65,000 Da; the minimum molecular mass upon SDS electrophoresis was 33,000 Da. The pH and temperature optima for the enzyme were 7.2-7.8 and 35 degrees C, respectively. The highest stability of catechol 1.2 dioxygenase II upon storage was observed in 50 mM Tris-HCl buffer pH 7.8 at 4 degrees C. The relative values of Vmax for catechol 1.2-dioxygenase II with 3 chloro-, 4-chloro-, and 3.5-dichlorocatechols were 28%, 50%, and 41% of those for catechol. The enzyme affinity for chlorocatechols was 3-9 times higher than for methylcatechols and 10-20 times higher than for unsubstituted catechol. PMID- 1294258 TI - [Isolation and properties of superoxide dismutase from human blood plasma]. AB - A procedure for purification of superoxide dismutase (SOD) from human blood plasma has been developed, which includes gel filtration on Ultrogels AcA-34 and AcA-44 (LKB, Sweden). The protein purified from blood plasma is a glycoprotein which is thermostable at 70-80 degrees C. The molecular mass of the protein determined immediately after gel filtration is approximately 147,000 daltons. A comparative analysis of effects on the SOD activity of plasma and erythrocytes of compounds capable of forming chelating complexes with metals within the enzyme active center has been carried out. The purified enzyme differs by its physico chemical characteristics from cytosolic Cu,Zn-SOD and pertains to a new class of SOD, the so-called extracellular SOD, detected in some biological fluids. PMID- 1294260 TI - A guide to human chromosome defects. PMID- 1294259 TI - [Energy metabolism and contractile function of the heart in diabetic cardiomyopathy: effect of ischemia and reperfusion]. AB - Physiological parameters, rates of mitochondrial respiration, high energy phosphate levels and creatine phosphokinase (CPK) activity were investigated in the hearts from control and alloxan-induced diabetic rabbits before and after 40 min total ischemia and reperfusion. Diabetic hearts demonstrated significant decreases in the rates of contraction (+dP/dt) and relaxation (-dP/dt), heart rates and cardiac work compared to control hearts. Determination of mitochondrial respiration rates in saponin-skinned fibers showed a low mitochondrial respiratory function in diabetic hearts. It was found that the ATP and ADP levels and the total and mitochondrial isoenzyme activities of CPK in diabetic hearts were lowered in comparison with control. A post-ischemic recovery of cardiac performance for diabetic hearts was better than in controls. After reperfusion diabetic hearts had increased ATP levels. The data obtained demonstrate some abnormalities of both cardiac performance and energy metabolism in the hearts of diabetic animals and a decreased sensitivity of the latter to ischemic injury. PMID- 1294261 TI - Improving access to prenatal care: innovative responses to a national dilemma. PMID- 1294262 TI - Problems with the international normalized ratio. PMID- 1294263 TI - Studies on gastroprotection induced by capsaicin and papaverine. AB - Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) but the possibility that NO mediates the protective and hyperemic effects of capsaicin and papaverine has been little studied. Using N-nitro-L-arginine (L-NNA), a selective blocker of NO synthase, and L-arginine as a substrate for NO, we investigated the role of NO in protective action of capsaicin and papaverine against ethanol-induced gastric damage and in GBF. Pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose-dependently the area of ethanol-induced lesions, the LD50 being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous (i.v.) injection of L-NNA (1.2-5 mg/kg), which by itself caused only a small increase in ethanol lesions, reversed dose-dependently the protective and hyperemic effects of capsaicin and papaverine against ethanol-induced damage and attenuated the increase in GBF induced by each of these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i.v.) but not by D-arginine. L-arginine partly restored the decrease in GBF induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), which suppressed the generation of PG by 85%, slightly enhanced the mucosal lesions induced by ethanol but failed to affect the fall in GBF induced by this irritant. Gastroprotective and hyperemic effects of capsaicin and papaverine were partly reversed by indomethacin suggesting that endogenous PG are also implicated in these effects. Addition of L-NNA to indomethacin completely eliminated both the protective and hyperemic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsaicin and papaverine on the gastric mucosa. PMID- 1294264 TI - Direct protective action of epidermal growth factor on isolated gastric mucosal surface epithelial cells. AB - Epidermal growth factor (EGF) protects gastric mucosa against acute injury produced by a variety of damaging agents, but the mechanism of its protective action is not clear. Since the surface epithelial cells (SEC) are important component of gastric mucosal defence, we studied whether EGF may directly protect isolated gastric SEC against ethanol injury in vitro, in condition independent of systemic factors and whether endogenous prostaglandins may play a role in EGF's protective action. The isolated SEC from rat gastric mucosa were preincubated in medium only, or medium containing 0.0001-10.0 micrograms/ml of h-rEGF for 15 minutes, and incubated with 8% ethanol for 1 hour. In another study the above experiment was repeated but cells were pretreated with 10(-4) or 10(-5) M indomethacin before EGF treatment. The cell viability was assessed by fast green exclusion test. Incubation of SEC with 8% ethanol significantly reduced SEC cell viability to 50 +/- 2%: EGF 0.1 or 1.0 microgram/ml significantly reduced ethanol induced damage (cell viability 59 +/- 3 and 62 +/- 3% respectively). Pretreatment with 10(-4) M indomethacin (the dose which does not affect SEC viability but inhibit PGE2 and PGI2 generation), significantly reduced protective action of EGF against 8% ethanol injury. EGF 1.0 and 10.0 micrograms/ml alone without ethanol increased PGE2 and 6 keto PGF1 alpha generation by SEC. These studies demonstrated: 1) EGF is able to protect gastric surface epithelial cells directly without mediation by systemic factors. 2) EGF induced protection of SEC may in part be mediated by prostaglandins. PMID- 1294265 TI - Platelet activating factor (PAF) inhibitor (TCV-309) reduces caerulein- and PAF induced pancreatitis. A morphologic and functional study in the rat. AB - Caerulein-induced acute pancreatitis was studied in rats. Consistent with this type of acute pancreatitis morphological (edema, leukocytic infiltration and acinar cell vaculization) and biochemical (increase in pancreatic protein content. PAF release and serum amylase) changes developed 5 hours after caerulein administration. In addition increase in pancreatic weight and decrease in pancreatic blood flow were noticed. PAF administration caused pancreatic damage similar in some parameters to caerulein-induced pancreatitis, along with reduction of pancreatic blood flow, increase in pancreatic protein content, and serum amylase. TCV-309, a selective PAF antagonist, administered prior to caerulein and/or PAF, reduced caerulein-induced pancreatitis and prevented PAF induced pancreatitis. Results of our present studies indicate the crucial role of PAF in pathogenesis of experimental acute pancreatitis. PMID- 1294266 TI - The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart. AB - The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG-nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG-nitro-L Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI2 and PGE2) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance. PMID- 1294268 TI - Induction of ornithine decarboxylase in normal and protein kinase C--depleted human colon carcinoma cells. AB - To examine the role of protein kinase C (PKC) in induction of human colon adenocarcinoma cell line, DETA/W, by polypeptide growth-promoting factors, ornithine decarboxylase activity (ODC) and DNA synthesis were determined in cells depleted of PKC. PKC depletion was achieved by prolonged cultivation (more than 30 passages) with 10(-6) M phorbol 12-myristate 13-acelate. Lack of PKC in studied cells was proved by measurements of PKC activity and immunoreactivity. Although ODC activities and DNA syntheses in PKC-depleted cells were decreased by about 40-50% compared to normal DETA/W cells, the percentage increase of these mitogen-responsive reactions was quantitatively similar in both cell sublines. These results raise the possibility that not all of the biological responses to growth factors are connected with the activation of calcium-dependent PKC. PMID- 1294267 TI - Vasopressin release from posterior pituitary lobe incubated in situ after preganglionic stimulation of the rat superior cervical ganglion. AB - In urethane-chloralose anaesthesia the pituitary gland was exposed by transpharyngeal approach in rats. The anterior lobe was removed and the posterior lobe was incubated in situ, that is in conditions of anatomical integrity of the hypothalamus with the posterior pituitary lobe. The 15-min samples of the medium incubating the posterior pituitary lobe in situ were collected. Vasopressin (AVP) content in the incubation medium was determined by radioimmunoassay. The stimulation of preganglionic fibers of the superior cervical ganglion (SCG) with alternate short (5 s) bursts of electric pulses with short (5 s) breaks did not change AVP release. However, stimulation of preganglionic fibres with alternate long (30 s) bursts of electric pulses with long (30 s) breaks evoked an increase in AVP release after some latency. Probably, at the hypothalamic or posterior pituitary level temporal summation should occur affecting vasopressinergic neurons or their endings and evoking AVP release. PMID- 1294269 TI - Human centrifugation: new approach in the treatment of diabetic background retinopathy (preliminary communication). AB - In previous studies we reported that Human Centrifugation Treatment (HCT) provoked endogenous prostaglandin liberation by a mechanical stimulus over the vessel walls. Up to now, the importance of Prostacyclin (PGI2) and HCT in the treatment of diabetic retinopathy has not been investigated. We studied the efficacy of one month of HCT in background retinopathy (BR). We evaluated the evolution of the visual acuity and the eye fundus at one, three six and one year after HCT in twenty-five patients. PGI2 levels were determined before and after HCT in seven patients and four normal volunteers. HCT was performed in a centrifuge Isasi's Model. Patients were exposed daily for 1 hour to acceleration profiles from head to feet during a period of a month. This preliminary communication demonstrated that: HCT provokes endogenous PGI2 liberation (p < 0.001), b) HCT substantially reduces vascular leakage and macular edema improving the visual acuity (p < 0.001); c) HCT has long-lasting beneficial effects. PMID- 1294270 TI - In vitro uptake of 18-hydroxycorticosterone by regions of the central nervous system. AB - The specific uptake of tritiated 18-hydroxycorticosterone (18-OH-B) by purified cell nuclear fractions and cytosol of medulla oblongata, pons, amygdala, anterior pituitary, hypothalamus, hippocampus, preoptic-area and lung from adrenalectomized animals was investigated after incubation of tissue sections with radioactive ligand. We found that 18-OH-B was taken up mainly by nuclei obtained from pons and medulla oblongata; this profile differs from previous observations with the closely related steroids corticosterone and aldosterone, which are mostly concentrated by the limbic system. Based on this finding, as well as on former studies with 18-OH-B, we suggest that this steroid may exert its action on renal excretion of protons as well as on central nervous system structures involved in respiratory regulation, related to that excretion. PMID- 1294271 TI - Time-dependency for the effect of different stressors on rat pineal melatonin content. AB - This study describes the effects of two stressors, swimming for 15 min or i.p. beta-carboline (beta-CCE) injection, on rat pineal melatonin levels when applied either at the end of the light period of daily photoperiod (1800 h) or at the expected melatonin maximum (at 2200 h). Neither procedure affected melatonin levels at 1800 h. In contrast, both stressors were effective to augment pineal melatonin content when applied at 2200 h. When applied at light-dark transition, only beta-CCE injection increased pineal melatonin levels at the middle of the night. Neither procedure was effective to counteract the inhibition of pineal melatonin content caused by prolonging the light phase for 4 h. Deprivation for two days of water, but not of food, augmented pineal melatonin levels in rats killed at the end of the light period, up to levels that were undistinguishable from those found at 2200 h. No differences were found between the two stressors and controls when tested at 2200 h. The present results further support the concept that stressful stimuli can influence differentially pineal melatonin production. PMID- 1294272 TI - [Evaluation of the method for early pregnancy factor detection (EPF) in swine. Significance in early pregnancy diagnosis]. AB - Early pregnancy factor (EPF) is a protein detected in the serum of pregnant females in most mammals, before implantation of the embryo; its activity is detected by the rosette inhibition test (RIT). After preincubation of lymphocytes in serum of non-pregnant pigs, the mean titre of RIT was 10.80 +/- 0.32. The upper limit of the 95% confidence interval was calculated to be 11.44. Therefore, all titres 12 were defined indicating the presence of EPF activity. The incubation of lymphocytes in serum of pregnancy caused a significant increase in the mean rosette inhibition titre, raising it to 19.88 +/- 1.13 (p < 0.001). False negative results were obtained for 10% of pregnant pigs. EPF positive activity was detected in only one non-pregnant pig (RIT = 20). This assay is not quantitative nor suitable for pregnancy diagnosis taking into account RIT values dispersion. PMID- 1294274 TI - [Abstracts of papers presented at XXXIV annual meeting of Japan Society of Smooth Muscle Research (I)]. PMID- 1294273 TI - Human centrifugation machine a physiological stimulator of endogenous prostaglandin synthesis. AB - A new model of human centrifugation machine with clinical purposes which makes possible to stimulate endogenous prostaglandin synthesis by a mechanical stimulus over the vessel walls is presented. The different therapeutical applications of this machine were demonstrated in lymphedema, peripheral obstructive arteriopathies, reflex sympathetic dystrophy syndrome, diabetic background retinopathy and coronary artery disease. PMID- 1294275 TI - [Abstracts of papers presented at the XXXIV annual meeting of the Japanese Society of Smooth Muscle Research (II)]. PMID- 1294276 TI - The effect of parental alcohol dependence on perceived children's behavior. AB - The effect of past-year parental alcohol dependence on perceived children's behavioral problems was assessed using data from a general population sample of 3,409 father-child pairs and 5,892 mother-child pairs. Eight percent of the children living in households containing fathers had an alcoholic father; 2% of those living with mothers had an alcoholic mother. Behavioral problems in the 3 months preceding the interview were assessed using a list of 32 indicators and were evaluated by an adult household member, usually the child's mother. The unadjusted odds of a child's being in the top 10th percentile of the behavioral problem distribution were increased by a factor of 1.7 for paternal alcoholism and 2.2 for maternal alcoholism. After adjustment for social and demographic characteristics of the child and family, the odds ratio for alcohol dependence in the mother dropped to 1.6; the odds ratio for paternal alcohol dependence remained at 1.7. Parental alcohol dependence did not interact with social and demographic factors in its association with children's behavioral problems. PMID- 1294277 TI - The relationship of dieting severity and bulimic behaviors to alcohol and other drug use in young women. AB - Patients with bulimia nervosa frequently have problems with alcoholism and other substance abuse. The goal of this study was to assess whether this relationship between eating abnormalities and substance abuse extends to subthreshold levels of dieting and substance use. A self-administered questionnaire assessing dieting and substance use (alcohol, cigarettes, and marijuana) was completed by 1,796 women prior to their freshman year in college. Using a scale derived from DSM-III R criteria for bulimia nervosa and previous research in this population, subjects were categorized as nondieters, casual, intense, severe, at-risk or bulimic dieters. The relationship between the dieting-severity category and frequency and intensity of alcohol use and frequency of marijuana and cigarette use was assessed. DSM-III-R criteria for bulimia nervosa were met by 1.6% of the women. Only 13.8% of these women were nondieters. Increasing dieting severity was positively associated with increasing prevalence of alcohol, cigarette, and marijuana use and with increasing frequency and intensity of alcohol use. The bulimic and at-risk dieters were similar in their alcohol and drug use. The relationship between eating disorders and alcoholism and other substance abuse noted in clinical populations extends in a continuous, graded manner to subthreshold levels of dieting and substance use behaviors. Dieting-related attitudes and behaviors in young women may be related to increased susceptibility to alcohol and drug abuse. PMID- 1294278 TI - The development and reliability of the RAATE-CE. AB - The Recovery Attitude And Treatment Evaluator-Clinical Evaluation (RAATE-CE) utilizes a brief, structured clinical interview that assesses five key dimensions that produce a clinically relevant and useful severity profile of the patient for making placement, continued stay, discharge, and treatment-planning decisions. The RAATE-CE also measures treatment progress. These five dimensions are: (A) degree of resistance to treatment (including denial of addiction problems); (B) degree of resistance to continuing care (including self-help groups); (C) acuity of biomedical problems; (D) acuity of psychiatric-psychological problems; and (E) the degree to which the psychosocial environment is supportive or detrimental to recovery. Data on 139 publicly funded, high-severity subjects suggest that the RAATE-CE demonstrates an interrater reliability across the five dimensions between .59 and .77, and an internal consistency reliability range between .65 and .87. PMID- 1294279 TI - Alcohol and anxiety: postdrink-performance feedback alters affective and self evaluative responses to a subsequent social stressor. AB - Several models of alcohol use and abuse implicate self-evaluation as a variable that mediates alcohol's anxiolytic effects. Self-evaluation when drinking, in turn, is affected by people's causal attributions for their behavior and alcohol expectancies. Accordingly, postdrink performance feedback was manipulated by having 20 subjects engage in a set of tasks before and after a moderate dose of alcohol. Half of the subjects received feedback that alcohol impaired their task performance whereas the other half received feedback that alcohol did not impair their performance. All subjects then participated in a stressful social interaction. As expected, subjects in the high behavioral impairment condition made more external performance attributions during the social stressor and reported less negative self-evaluation and subjective anxiety than subjects in the low behavioral impairment condition. Alcohol expectancies appeared to account partially for the data. The results indicate that information concerning alcohol induced behavioral impairment moderates alcohol's effects on self-evaluation and subjective anxiety. PMID- 1294280 TI - A Cocaine High-Risk Situations Questionnaire: development and psychometric properties. AB - Although high-risk situations have been identified for alcoholism, opiate abuse, and smoking, further research is needed to identify high-risk situations for cocaine abuse. A 233-item Cocaine High-Risk Situations Survey was developed based on a comprehensive literature review and was administered to 179 cocaine users in treatment. Situations that occurred infrequently or that were not often associated with cocaine use were eliminated and the remaining 89 items were factor analyzed using half the sample with confirmatory factor analysis on the remainder of the sample. Only one factor was found for frequency of cocaine use in these situations. The 21 items with high factor loadings and a diverse range of content were retained for subsequent analyses and renamed the Cocaine High Risk Situations Questionnaire (CHRSQ). Reliability and convergent and discriminant validity of this scale were demonstrated. Frequency of alcohol use in the same situations was not significantly related to cocaine use and abuse, supporting discriminant validity. The findings suggest that the frequency of ongoing cocaine use is not determined by specific situations. Theoretical and clinical implications are discussed. PMID- 1294281 TI - Alcohol use and personality relationships in U.S. and Polish adolescents. AB - To obtain information, which could be useful to the design of intervention and prevention programs for adolescent alcohol users and potential users, personality and alcohol use data were collected from over 300 Polish and U.S. 15-year-olds. Thirty percent of these subjects were already drinking on a more or less consistent basis. Users were angry, nonconforming, and impulsive-antisocial persons in both countries. Future research and potential intervention and prevention strategies are discussed. PMID- 1294282 TI - Observer reports of smoking status: a replication. AB - Observer and self-reports of abstinence from smoking were compared at 2-, 7-, 14 , 30-, 90-, and 180-day follow-ups and with biochemical verification at 180-day follow-up in a study of 630 self-quitters. Observer reports were often not returned (25-65%), rarely refuted self-reported abstinence (< 1%), and were often discordant with biochemical results (32%). These results replicate a prior finding (Hughes, 1990) that observer verification of smoking status during a prospective study of cessation is not very helpful. PMID- 1294283 TI - [Characteristics of the radioprotective and radiotherapeutic effect of serotonin on mammalian embryo development]. PMID- 1294284 TI - [A mathematical model of kinetic activation of blood coagulation factors VII and X]. PMID- 1294285 TI - Basic fibroblast growth factor high and low affinity binding sites in developing mouse brain, hippocampus and cerebellum. AB - Fibroblast growth factors (FGFs), first extracted from brain and retina, are potent neurotrophic factors. They stimulate neuroblast proliferation and neuron differentiation and survival. In order to study the spatial and temporal distribution of the target cells in the mouse brain we studied by autoradiography and quantified by image analysis 125I-bFGF binding sites as a function of development. We have revealed the presence of two types of specific bFGF receptors. One is heparitinase sensitive and is co-localized with heparan sulfate proteoglycans of the basement membranes (meninges, choroid plexus and blood vessels). It is not developmentally regulated and corresponds to the low affinity receptors. It may be a storage form. The second type is heparitinase resistant and is modified during development, matching, in the adult, layering of the hippocampus and cerebellum. At 13 days of embryonic development there is a preferential distribution of silver grains on the ecto- and neuroectodermal tissues. In the adult, the labeling is localized on the neural process layers. It likely corresponds to the specific binding to cell high affinity receptors. Binding patterns according to the developmental stages of the brain can be correlated with mitotic, migration and differentiation phases of the neuronal cells. PMID- 1294286 TI - The role of calcium, polyamines and centrosomes in the formation and organization of cleavage furrows in amphibian eggs. AB - Cleavage furrows of amphibian eggs exhibit characteristic morphological features: the presence of finger-like microvilli (MV) along their outer edges, the formation of furrow walls from new plasma membrane lacking MV, and the subsequent retrieval of this membrane during the infolding of the furrow. A similar structure can be induced, specifically, by certain cytoplasmic components such as centrosomes, polyamines and calcium. Their respective roles in the events associated with the furrowing process have been investigated by injecting these agents into nucleated and enucleated Pleurodeles eggs and evaluating their effects using cytochemical labelling of the egg surface with a biotin streptavidin system. The injection of polyamines (spermine or spermidine) and in some cases, calcium into enucleated eggs provoked MV elongation and the appearance of newly formed, smooth plasma membrane. In these eggs, this membrane was not incorporated into the furrows, and as a consequence, the blastomeres did not actually separate. In contrast, the injection of centrosomes into enucleated eggs induced both the incorporation and internalization of new membrane, resulting in the formation of furrows and a true cellularization of the eggs, identical to the cleavage process observed in fertilized eggs. The present results provide further evidence that the establishment of the furrow depends on two complementary interacting systems: the contractile elements of the egg cortex which regulate the insertion of new membrane and the mitotic center which is essential for the invagination of the furrow. PMID- 1294287 TI - Structure of the mouse gene encoding peripherin: a neuronal intermediate filament protein. AB - The gene encoding mouse peripherin, a neuronal intermediate filament protein, has been cloned. Its sequence, through 1021 nucleotides composing the 5'-flanking region, nine exons, eight introns and 547 nucleotides of the 3'-flanking region, as well as its transcription initiation site have been determined. The amino acid coding sequence differs from that of the rat peripherin gene. The mouse gene has an additional histidine near the N-terminal end, and shows three conservative and two non-conservative changes. The promoter sequence, containing the binding sites for transcription factors as well as other sequences is homologous to promoter regions of other type III intermediate filament protein genes and other neuronal specific genes. PMID- 1294288 TI - Changes in retinal pigment epithelial cell autofluorescence and protein expression associated with phagocytosis of rod outer segments in vitro. AB - The accumulation of autofluorescent lipofuscin was quantified in cultured human retinal pigment epithelial (RPE) cells phagocytosing bovine rod outer segments (BROS) and the expression of proteins in these cells was investigated. Results showed a steady increase in autofluorescence of RPE cells over a 4-week period as measured by fluorophotometric flow cytometry. A significantly greater increase in autofluorescence was found in the cultured RPE cells from a 7-year-old donor compared with those from a 47-year-old donor. Within both groups the BROS challenged cells had significantly higher fluorescence readings than the control cells which were not challenged. Autoradiography of 35S-labelled proteins separated by polyacrylamide gel electrophoresis (PAGE) revealed a small distinct band at 102 kDa in BROS-challenged RPE cells of both bovine and human origin that did not appear in control or microsphere-phagocytosing RPE cells. The intensity of the signal was unrelated to the duration of the challenge period. PMID- 1294289 TI - Principal and intercalated cells in primary cultures of rabbit renal collecting tubules revealed by monoclonal antibodies. AB - In this study we describe the production and characterization of two monoclonal antibodies (mAb 503 and mAb 703) raised against the apical membrane of rabbit cortical collecting tubule (CCT) cells. The specificity of the two monoclonal antibodies was studied by immunoelectron microscopy on kidney sections. These antibodies were used to identify principal and intercalated cells in primary cultures of CCT. To assess the maintenance of the basic characteristics of the cortical collecting cells during the growth process we determined the biochemical and electrophysiological properties of cultured CCT. Of the monoclonal antibodies produced mAb 503 was specifically directed against the luminal membrane of intercalated cells as shown by immunoelectron microscopy. mAb 703 bound specifically the apical membrane of the principal cells. In primary cultures of CCT mAb 503 and mAb 703 bound antigens present on the apical membrane of different cells and permitted the study of the distribution of the two cell types. Results showed the maintenance of the epithelial polarity of cultured CCT and the expression of specific antigens. PMID- 1294290 TI - D-galacturonic acid derivatives as acceptors and donors in glycosylation reactions. AB - Jones oxidation of suitably protected allyl beta-D-galactopyranosides and subsequent esterification were reinvestigated. Partial deprotection of the resulting D-galacturonic acid derivatives afforded compounds suitable for transformation into glycosyl acceptors. The synthesis of 2-, 3-, and 4-trityl ethers, relying on efficient differential protecting-group strategies, is described. Trityl-cyanoethylidene condensation of these trityl ethers, leading to the protected disaccharide units beta-D-GalpA-(1-->2)-D-GalpA and beta-D-GalpA-(1 ->3)-GalpA with high stereoselectivity, is demonstrated. A beta-D-GalpA-(1-->4)-D GalpA disaccharide was also prepared. PMID- 1294291 TI - Synthesis of a heteroglycuronan derivative containing the beta-D galactopyranosyluronic acid (1-->3)-L-rhamnose repeating unit. AB - Helferich glycosylation of the cyanoethylidene L-rhamnose derivative 3 with the galactosyluronic bromide 2 gave the disaccharide 4 as a key intermediate in the synthesis of the monomer 13 for trityl-cyanoethylidene condensation (TCC). The following formation of the monomer 13, including introduction of a trityl group at O-3', proceeded in six steps. Because of the difficulty of some steps, an alternative route for 13 was tested. Model compounds 20, 21, and 22 were synthesized in order to confirm the stereoregularity of the products of the polycondensation. The polycondensation of the monomer gave D-GalpA-(1-->3)-L-Rha oligomer derivatives consisting mainly of three repeating units. This result is in contrast with the degree of polymerisation (dp > or = 22) of other synthetic rhamnans, but is very similar to dp 2-7 of homo- and hetero-glucuronan derivatives. PMID- 1294293 TI - Synthesis of (+)- and (-)-nojirimycin and their 1-deoxy derivatives from myo inositol. AB - The conversion of the naturally abundant cyclitol, myo-inositol (4), into (+) nojirimycin (1a), its enantiomer (1b), and their 1-deoxy analogues (2a and 2b) is described. Biological assay of 2a, 2b, and the bisulfite adducts of 1a and 1b (3a and 3b) showed that the compounds having the unnatural L-gluco configuration (2b and 3b) possess moderate-to-high inhibitory activity against almond beta-D glucosidase and bovine liver beta-D-galactosidase. PMID- 1294292 TI - Strong competitive inhibition of porcine pancreatic alpha-amylase by aminodeoxy derivatives of maltose and maltotriose. AB - The syntheses are described of 6-amino-6-deoxymaltose (2), the 6-amino-6-deoxy (4), 6'-amino-6'-deoxy (6), and 6"-amino-6"-deoxy (8) derivatives of maltotriose, and the methyl alpha- (10) and beta-glycoside (12) and the 1-deoxy derivative (16) of 4. The Ki values (microM) of these competitive inhibitors of porcine pancreatic alpha-amylase were: 2, 88; 4, 1.9; 6, 2.0; 8, 175; 10, 360; 12, 9000; 16, 7600 (cf. 1800 for maltotriose and 3000 for methyl alpha-maltotrioside). The low values for 4 and 6 reflect reinforcement of the normal binding by ionic attraction and, possibly, interaction of the reducing end groups with the protein. PMID- 1294294 TI - 1H and 13C NMR study of nonsymmetrical alpha,alpha-trehalose derivatives. PMID- 1294295 TI - Sulfate composition of dermatan sulfate from scar tissue. PMID- 1294296 TI - Crystal structure of methyl 3-O-beta-D-glucopyranosyl-beta-D-glucopyranoside (methyl beta-D-laminarabioside) monohydrate. AB - Crystals of methyl 3-O-beta-D-glucopyranosyl-beta-D-glucopyranoside (methyl beta D-laminarabioside) belong to the orthorhombic system, space group P2(1)2(1)2, with a = 14.548(2), b = 24.252(7), c = 4.938(1) A, and Z = 4. The crystal structure was solved by the direct method and refined by the full-matrix least squares procedure to an R-value of 0.062 for 1099 observed reflections in the X ray data. The molecular structure is similar to that of beta-D-laminarabiose. The torsional angles around the glycosidic bonds are influenced by both the existence of an intramolecular hydrogen bond at O-4'... O-5 and the exo-anomeric effect. In the nonreducing residue, the exocyclic O-5-C-5-C-6-O-6 and C-4-C-5-C-6-O-6 torsional angles are (+)gauche and trans, respectively, whereas the corresponding torsional angles in the reducing residue are (-)gauche and (+)gauche. One water molecule cocrystallizes with each disaccharide, and the crystal structure is stabilized mainly by intra- and inter-molecular hydrogen bonds involving water molecules. PMID- 1294297 TI - A 1H NMR study of a fragment of partially n-acetylated chitin produced by lysozyme degradation. PMID- 1294298 TI - Synthesis and 13C NMR spectra of 2,3-di-O-glycosyl derivatives of methyl alpha-L rhamnopyranoside and methyl alpha-D-mannopyranoside. AB - The syntheses are described of 2,3-di-O-glycosyl derivatives of methyl alpha-L rhamnopyranoside (1-5) and alpha-D-mannopyranoside (6-9). [formula: see text] [table: see text] The deviation from additivity in 13C NMR spectra calculated for 1-9 were similar for stereochemically related trisaccharides. PMID- 1294299 TI - Effects of fluoride and methanehydroxydiphosphate on enamel and on dentine demineralization. AB - The aim of this article was to investigate the effects of methanehydroxydiphosphonate (MHDP) and fluoride (F) separately and combined, on the demineralization process in enamel and in dentine under constant composition conditions. The demineralization was carried out in solutions containing 3 mM calcium, 3 mM phosphate, pH = 5.0, and either 6 microM MHDP, 12 microM F or 6 microM MHDP and 12 microM F. After demineralization periods (t) between 24 and 140 h, the lesion depth l and the mineral loss delta Z were measured by transverse microradiography of the enamel and dentine specimens. The amount of mineral lost during demineralization averaged over the lesion depth, R = delta Z/l, was calculated. R approximately 17 vol% for both enamel and dentine, both delta Z and l being greater for dentine than for enamel by approximately the same factor. The results show that under the same conditions dentine is attacked much more strongly than enamel. The lesion progress with time is quite different for the two tissues: in enamel the lesion depth progresses als l3 = alpha t + beta, in dentine as l2 = alpha't + beta'. The slopes alpha and alpha' decrease in the order MHDP > F > MHDP+F. In enamel the combined inhibitor effect is only slightly larger than the effect of F alone; in dentine the inhibiting effects of F and MHDP are approximately additive. The inhibitor interactions can be described by the Langmuir adsorption theory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294301 TI - Salivary clearance from different regions of the mouth in children. AB - The aim of this study was to evaluate the rates of salivary clearance at seven different locations in children. The diffusant was 1 mol/l KCl in a 1.0% agarose matrix, placed in small acrylic devices which could be fastened to the teeth with dental floss. The diffusion chambers were taken from the mouth at selected time intervals and the gels transferred quantitatively to flasks containing 400 ml of 100 ppm NaCl. The fluid was agitated intermittently for 1 h and analyzed for potassium by atomic absorption spectrophotometry. For 12 subjects (5 years of age), the clearance halftimes (the time for the initial potassium concentration to decrease by half) were lowest in the lower anterior lingual regions and were highest in the upper anterior buccal regions. When the salivary flow was stimulated, the clearance halftimes for the lower and upper anterior buccal sites in the 6 subjects without spaces between their anterior teeth were significantly higher than in the 6 subjects with spaces. The results show that the clearance halftime is longest for the upper anterior buccal site which is the site most prone to nursing bottle caries in the deciduous dentition. PMID- 1294300 TI - Influence of occlusion on the fluoride distribution in rat molar cementum. AB - This study was undertaken to examine the influence of occlusion on the fluoride distribution in cementum following an experiment in which the occlusion in rats was locally altered by extracting the upper left molar. These and control rats with normal occlusion were given water containing 0 or 100 ppm fluoride for 12 weeks. The fluoride distributions in cementum from both first lower molars of the same animal were compared. The fluoride concentrations had increased throughout the tissue as a result of increased fluoride administration, irrespective of any changes in occlusion. They were, as usual, generally highest at or near the cementum surface and decrease towards the interior of the tissue. Where there had been a change in occlusion, the thickness of cementum was less than that of the contralateral tooth, but, despite this, the fluoride profiles in contralateral teeth were similar in both experimental and control rats. In the experimental rats, on the other hand, the total fluoride tended to be lower, and the mean fluoride tended to be higher in left molars without antagonists. These findings were never seen in the control rats. It was concluded that the alteration in occlusion influenced the fluoride distribution in the cementum through its effect on the rate of cementum formation. PMID- 1294303 TI - Effect of different glass ionomers on the acid production and electrolyte metabolism of Streptococcus mutans Ingbritt. AB - In order to study the effects of different glass ionomers on the metabolism of Streptococcus mutans, test slabs of freshly mixed conventional glass ionomer (Fuji), silver glass ionomer (Ketac-Silver), composite (Silux), and 2-week-old Fuji were fitted into the bottom of a test tube. A plaque-like layer of S. mutans strain Ingbritt was centrifuged onto the test slabs, and the samples were incubated for 20 h in 1.7% (w/v) sucrose solution. For freshly mixed Fuji and Ketac-Silver, the pH fall was significantly smaller than for old Fuji and composite. These materials also released the largest amount of fluoride into the fluid phase. Incubation with glass ionomer materials led to an increase in the cellular concentration of fluoride in bacteria, but intracellular fluoride did not correlate with the fall in pH. The lowest pH was associated with the lowest cellular magnesium content. Ketac-Silver released large amounts of calcium in the fluid phase, and the cellular calcium content was doubled in this group. The results show that freshly mixed glass ionomers affect acid production and electrolyte metabolism of S. mutans in vitro. The effect of conventional glass ionomer, however, seems to disappear after a few weeks. The effects of calcium and silver released by cermet glass ionomer deserve further study. PMID- 1294302 TI - Plaque formation in vivo and bacterial attachment in vitro on permanently hydrophobic and hydrophilic surfaces. AB - Highly hydrated polyethylene oxide (PEO) films represent one type of surface modification which may interfere with biofilm formation. Protein adsorption and saliva-mediated bacterial adherence were investigated in vitro on normal and hydrophobized glass surfaces and on glass surfaces with immobilized PEO films. More protein and bacteria bound to untreated compared to hydrophobized and PEO treated glass. Pellicle and plaque formation was also studied in vivo on ceramic crown surfaces either untreated, hydrophobized or with immobilized PEO films. Pellicle and plaque formation was similar on the untreated ceramic and PEO surfaces. Less plaque seemed to collect on these surfaces compared to adjacent normal tooth surfaces. Almost no plaque accumulated on the hydrophobic crown surface and it was virtually devoid of stainable pellicle. Even after 7 days in the mouth without oral hygiene this surface was very hydrophobic and the disclosing solution could not spread. PMID- 1294305 TI - Validity of probing for fissure caries diagnosis. AB - One hundred extracted molar teeth with discoloured fissures but without any visible carious cavitation were selected from a large supply, using standardized criteria. The teeth were mounted, placed on a mechanical balance, and probed with a force of 500 g in every fissure, at as many places as possible. Every time the probe was found to stick, the spot was marked. After probing colour slides were made of the occlusal faces. Subsequently, the crowns were embedded in epoxy resin. 700 microns thick sections were cut in a facial-lingual direction with a diamond wheel. From the sections X-rays were taken which were scored as follows: a measuring grid was placed on the X-ray image of a section, and the caries score (0-4) for every millimetre was determined. By scoring every section of a tooth in this way, an overview was obtained of the location of all caries lesions in the occlusal surface. By comparing this overview with the colour slide of the tooth, the relationship between the sticky spots and the lesions was visualized. The results indicate that only 24% of the caries lesions were discovered by probing for stickiness (low sensitivity), but that the probe seldom stuck in a sound fissure (high specificity, > 99%). Probing proved to be unreliable for the diagnosis of fissure caries. PMID- 1294304 TI - Oral sugar clearance and root caries prevalence in rheumatic patients with dry mouth symptoms. AB - The relationship between root caries, oral sugar clearance, salivary flow rate, and salivary counts of mutans streptococci, lactobacilli and candida has been studied in a group of 22 rheumatic patients (age range 40-72 years). The study group comprised all subjects volunteering for a clinical trial on relief of dry mouth symptoms. The median salivary flow was 0.09 ml/min at rest and 0.9 ml/min during chewing stimulation. The median sugar clearance time was about 5 min in the sublingual area and 16 min in the lower buccal vestibule. For subjects with 0 2 root caries lesions the clearance time at both sites was shorter than for subjects with 3 or more lesions (p < 0.05). A long oral clearance time was significantly correlated with age, root caries (DS and DFS), low resting salivary flow, and high salivary counts of mutans streptococci. It is concluded that root caries in rheumatic patients with low salivary flow is significantly related to oral sugar clearance time. PMID- 1294306 TI - Prediction of root caries in periodontally treated patients maintained with different fluoride programmes. AB - The aims of the investigation were to evaluate the effect of different fluoride programmes, as adjuncts to professional plaque control every 3-4 months, on root caries incidence in periodontally treated patients and to identify risk factors for root caries development. Ninety-nine individuals, 33-76 years old, who had been treated for periodontal disease were subjected to one of three fluoride programmes during a 2-year period: (1) professional application, 3-4 times/year, of Duraphat (n = 34) or (2) of a 0.4% stannous fluoride gel (n = 33), or (3) daily mouthrinsing with a 0.05% sodium fluoride solution (n = 32). A number of clinical recordings and laboratory tests, used as presumptive risk indicators for root caries, were carried out before and on three different occasions after the periodontal treatment. No statistically significant differences were found between the various fluoride programmes. During the 2-year period, a total of 246 new decayed or filled surfaces (DFS) were recorded, 72 (29.3%) of which were diagnosed as active and 124 (50.4%) as inactive root caries lesions; 50 (20.3%) of the surfaces had been restored. Individuals with > or = 1 new root DFS during the 2 years (n = 50) differed significantly from those with 0 new root DFS (n = 49) as concerns salivary counts of mutans streptococci and lactobacilli, root plaque scores and percentage of exposed root surfaces. Baseline root caries prevalence (r = 0.43) and root plaque scores (r = 0.36) showed the highest correlations with new root DFS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294307 TI - Prevalence and intraoral distribution of coronal and root caries in middle-aged and older adults. AB - This work describes the prevalence and intraoral distribution of coronal and root caries in 326 predominantly white, educated, middle-aged and older adults. Study participants were recruited from Tufts Geriatric Outreach Program, Nutritional Status Study (NSS), and the Forsyth Root Caries Study. Eighty-five percent of participants reported visiting their dentist in the last year. The median number of teeth was 21 in the 65+ age-group, and 40% of participants had coronal caries and 33% had root carious lesions. The mean coronal and root caries (DFS) was higher and the proportion of decayed surfaces to all decayed and filled surfaces (%D/DFS) was lower than in other comparable studies. A comparative analysis of intraoral distribution of coronal and root caries and their relation with age is discussed. PMID- 1294308 TI - Time trends in caries experience of children in England and Wales. AB - Regular national surveys of child and adult dental health and regionally coordinated surveys of caries experience in children provide a comprehensive picture of secular changes in disease levels in England and Wales. The substantial decrease in mean dmft in 5-year-olds between 1973 and 1983, amounting to 7.7% per annum, slowed to 0.9% per annum between 1983 and 1989/90. Conversely the decline in DMFT in older children and adolescents has accelerated more than twofold since 1983. In some parts of the country, caries experience at 5 years has shown a small increase and possible reasons for this are discussed. The validity of the survey data is examined and ways of consolidating and maintaining the downward trend in disease are considered. PMID- 1294309 TI - [The importance of detection of antigliadin antibodies in the diagnosis and therapy of celiac disease in children]. AB - The authors describe the method of assessment of antigliadin antibodies class IgA and IgG by the ELISA method. In a group of children with untreated coeliac disease the antigliadin antibodies were elevated in 91.6%, in a group of children with coeliac disease after exposure to gluten in 87.8%, in children on a gluten free regime in 48.5%. The dynamics of antigliadin antibodies in the course of the first year are presented--their decline in serum of children suffering from acute coeliac disease after elimination of gluten and conversely their rise after discontinuation of the gluten-free diet in children previously treated for prolonged periods. The sensitivity of the assessment is 91.6% and the specificity 90.6%. PMID- 1294310 TI - [The effect of breast feeding on morbidity in children]. AB - The authors investigated in a group of 4210 children from birth to three years from Southern Moravia the morbidity from respiratory infections, diarrhoea and other infections. There were bisexual differences in morbidity, girls were less frequently ill. Children from child communities had a two old morbidity. Birth order was also important. The influence of natural nutrition was apparent in particular during the first year when infants breastfed for more than 4 months had significantly fewer spells of illness. These results were influenced by sex and birth order. At the age of two and three years the differences between children breastfed for a short and long time disappeared. Similar results were found also in other morbidity indicators such as administration of antibiotics, number of hospital admissions and mean number of days spent in hospital. PMID- 1294311 TI - [Morbidity in children up to 1 year of age and factors affecting it during a longitudinal prospective study]. AB - During a longitudinal survey of 5154 children under one year the morbidity was investigated and the influence of some psychosocial, socioeconomic and oecological factors which influence morbidity. These are partial results of a long-term research project. PMID- 1294312 TI - [Intraosseous infusions in children]. AB - The authors submit a review on th intraosseous approach to infusions and their possible application in emergency medicine. PMID- 1294313 TI - [Pharmacokinetics of sulfamethoxazole in childhood]. PMID- 1294314 TI - [ACE inhibitors--a prospective new group of drugs for the treatment of kidney diseases]. AB - ACE inhibitors which till recently were used only in the treatment of cardiovascular diseases are becoming a perspective group of drugs also in the treatment of chronic nephropathies. It was revealed that they are effective in particular in the treatment of proteinuria of different etiology and have also a marked renoprotective effect and are therefore recommended to slow down the progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard the progression of chronic glomerulonephritis and diabetic nephropathy. It may be excepted that their therapeutic application will in the near future be extended also to clinical nephrology. PMID- 1294315 TI - [The importance of a rapid, direct method of detection of group A streptococci in the treatment of pharyngitis]. PMID- 1294316 TI - [Bronchomotor tests in asthma associated with running]. PMID- 1294317 TI - Constituents of the roots of Cynanchum bungei Decne. Isolation and structures of four new glucosides, bungeiside-A, -B, -C, and -D. AB - Four new glucosides, bungeiside-A, -B, -C, and -D, were isolated from the roots of Cynanchum bungei Decne. The structures of the new compounds were determined by chemical and spectroscopic methods, including two-dimensional nuclear magnetic resonance (2D NMR) techniques, especially 1H-detected heteronuclear multiple-bond multiple-quantum coherence. PMID- 1294318 TI - Resin glycosides. XV. Simonins I-V, ether-soluble resin glycosides (jalapins) from the roots of Ipomoea batatas (cv. Simon). AB - Five new ether-soluble resin glycosides (jalapins), simonins I-V, have been isolated from the roots of Ipomoea batatas and characterized on the bases of chemical and spectral data. Simonin I is the first example of resin glycoside with aromatic acid (trans-cinnamic acid) as a component organic acid. PMID- 1294319 TI - Repandiol, a new cytotoxic diepoxide from the mushrooms Hydnum repandum and H. repandum var. album. AB - Repandiol, a new cytotoxic diepoxide has been isolated from the mushrooms Hydnum repandum and H. repandum var. album. The chemical structure was elucidated as (2R,3R,8R,9R)-4,6-decadiyne-2,3:8,9-diepoxy-1,10-diol on the basis of spectroscopic analysis. The structure was confirmed by the synthesis of optically active repandiol. Repandiol displayed potent cytotoxic activity against various tumor cells. PMID- 1294320 TI - Russuphelin A, a new cytotoxic substance from the mushroom Russula subnigricans Hongo. AB - A new cytotoxic substance, designated russuphelin A (1), has been isolated from the mushroom Russula subnigricans Hongo (Basidiomycetes). The structure was elucidated as 2,6-bis(2,6-dichloro-4-hydroxyphenyloxy)-1,4-dimethoxy-benzene on the basis of spectroscopic data and confirmed by total synthesis. PMID- 1294321 TI - 5-Lipoxygenase inhibitors isolated from the mushroom Boletopsis leucomelas (Pers.) Fayod. AB - Terphenyl compounds, tentatively named Bl-I (1), Bl-II (2), Bl-III (3), Bl-IV (4) and Bl-V (5), showing 5-lipoxygenase inhibitory activity have been isolated from the mushroom Boletopsis leucomelas (Pers.) Fayod. On the basis of physico chemical and spectral evidence, they were concluded to be a series of cycloleucomelone-leucoacetates. PMID- 1294322 TI - Studies on antiplatelet agents. I. Synthesis and platelet inhibitory activity of 5-alkyl-2-aryl-4-pyridylimidazoles. AB - 5-Alkyl-2-aryl-4-pyridylimidazoles were synthesized and tested in rat ex vivo platelet aggregation studies. Among these compounds, 2-(2-fluorophenyl)-5-methyl 4-(3-pyridyl)imidazole (25) was most potent, and showed 98% inhibition at a dose of 10 mg/kg (p.o.). 25 had inhibitory activity on cyclooxygenase, thromboxane A2 (TXA2) synthetase, and phosphodiesterase, and also showed inhibited KCl-induced contraction of rat aorta. All compounds have little acute toxicity and appear to be free of adverse effects on the stomach. PMID- 1294324 TI - Stability in aqueous solution of two monocyclic beta-lactam antibiotics: aztreonam and nocardicin A. AB - The catalytic effect of various buffer systems (citrates, acetates, phosphates, borates and carbonates) on the degradation of aztreonam and nocardicin A in aqueous solution was studied at 35 degrees C and a constant ionic strength of 0.5 mol.dm-3 over a pH range of 3.50 to 10.50. The observed degradation rates, obtained by measuring the remaining intact antibiotic, were shown to follow pseudo-first-order kinetics with regard to antibiotic concentrations and to be influenced by general acid and general base catalysis. The changes in the concentration of intact beta-lactam antibiotic in the solutions were established by reverse-phase HPLC with UV-detection. In general the buffer systems employed in the kinetic studies showed a very weak catalytic effect on the degradation of aztreonam and nocardicin A. The pH-rate profiles for these antibiotics showed degradation minimums at pH 5.38 and 6.13, respectively. Aztreonam is slightly more reactive with hydrogen ions than nocardicin A and is much more reactive with hydroxide ions. In comparison with other beta-lactamic antibiotics, aztreonam and nocardicin A are much more stable in aqueous solution, except for aztreonam in a base solution, which is just as unstable as penicillins and cephalosporins. The Arrhenius activation energies were determined for aztreonam and nocardicin A at pH's 4.23, 6.59 and 8.60. PMID- 1294323 TI - Renin inhibitors. II. Synthesis and structure-activity relationships of N terminus modified inhibitors containing a homostatine analogue. AB - The synthesis and structure-activity relationships of N-terminus modified renin inhibitors containing the homostatin analogue, (2RS,4S,5S)-5-amino-2-ethyl-4 hydroxy-7-methyloctanoic acid, are described. The compounds having a 3-alkyl (or aryl)sulfonylpropionyl residue at the N-terminus are found to be potent inhibitors which contain two amino acids. (2RS,4S,5S)-N-Isobutyl-5-[N-[(2S)-3 ethylsulfonyl-2-(1- naphthylmethyl)propionyl]-L-norleucyl]-amino-2-ethyl-4 hydroxy-7- methyloctanamide (20) has an IC50 of 0.5 nM against human plasma renin and the oral bioavailability of 20 is 0.73% in rats. Interaction between renin and the N-terminus of 1 and 20 is discussed in molecular modeling studies. PMID- 1294325 TI - Catalysis of hydrolysis and aminolysis of non-classical beta-lactam antibiotics by metal ions and metal chelates. AB - The Zn(2+)-tris (hydroxymethyl)aminomethane (Tris) system has a great catalytic effect on the hydrolysis and aminolysis of some beta-lactam antibiotics. In order to ascertain the mechanism of this catalysis we have analysed the effects of the beta-lactam antibiotic structure. First we studied the kinetics of the decomposition of imipenem, SCH 29482, aztreonam and nocardicin A in aqueous solution of Tris at 35.0 degrees C, 0.5 mol.dm-3 ionic strength and in the presence of metal ions (Zn2+, Cd2+, Co2+, Cu2+, Ni2+ and Mn2+). From these studies, we conclude that Tris and metal ions (in separate solutions) exert a great catalytic effect on the hydrolysis of imipenem and SCH 29482. We suggest that in metal ion solutions a 1:1 complex is formed between the metal ion and beta-lactam antibiotic, which is attacked by hydroxide ions. Studies of the degradation of the antibiotics studied in solutions of Tris and metal ions together indicate that the systems Cd(2+)-Tris and Zn(2+)-Tris have a great catalytic effect on the hydrolysis and aminolysis of imipenem and SCH 29482. We suggest that this catalysis takes place via a ternary complex in which the metal ion plays a double role by (a) placing the antibiotic and the Tris in the right position for the reaction and (b) lowering the pKa of the hydroxide group of Tris, which is coordinated with the metal ion, generating a strong nucleophile. PMID- 1294327 TI - New bronchodilators. II. 3H-imidazo[4,5-c]quinolin-4(5H)-ones. AB - A series of novel 3-substituted imidazo[4,5-c]quinolin-4(5H)-ones (2a-w) was prepared by the reaction of imidazo[4,5-c]quinolin-4(5H)-ones (6) with several electrophiles under basic conditions. The bronchodilatory activity of these compounds was evaluated on the basis of their protective effects against antigen induced contraction (the Schultz-Dale reaction) of guinea-pig trachea (in vitro) and antigen inhalation-induced bronchospasm in passively sensitized guinea-pigs (in vivo). Although correlations between in vitro and in vivo activities were not clear, short alkyl chains such as the methyl and ethyl groups at the 3-position were important for potent activity, especially in vivo. Substituents at the 5 position were more tolerant of the activity than those at the 3-position. 5-Ethyl 3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one (21) exhibits the most potent bronchodilatory activity among our tested compounds and is at least 5-fold more active than theophylline in vivo. PMID- 1294326 TI - Nematocidal activity of long alkyl chain amides, amines, and their derivatives on dog roundworm larvae. AB - The nematocidal activity of amides and amines having a long alkyl chain against the second-stage larva of dog roundworm, Toxocara canis, was examined. Long chain acyl amides with smaller substituents on the nitrogen showed stronger activity and the activity of cyclic amine amides was stronger than that of acyclic ones. In a series of homologous amides, the activity was dependent on the alkyl chain length: it reached a maximum at an optimal chain length and decreased in both shorter and longer homologues. The relationship between the activity and hydrophobicity of the homologues was analysed by the use of the bilinear model. The hydrophobicity of a compound, which gives a maximal activity, was similar for all neutral amides, but amides which have an additional amine group in the molecule had different values. Tertiary amines and their salts having a long alkyl chain also showed nematocidal activities comparable to those of the corresponding amides. The salts killed the larva at concentrations lower than their critical micell concentration, suggesting that they behave as a single molecule for the nematocidal action. PMID- 1294328 TI - Amino acids and peptides. XVI. Synthesis of N-terminal tetrapeptide analogs of fibrin alpha-chain and their inhibitory effects on fibrinogen/thrombin clotting. AB - N-Terminal tetrapeptide analogs of fibrin alpha-chain were synthesized by the solution method using a new active ester, the ester of the oxime of p nitroacetophenone, and by the solid-phase method. Their inhibitory effects on fibrinogen/thrombin clotting were examined. Of the synthetic peptides, amide analogs of Gly-Pro-Arg-Pro exhibited a more potent inhibitory effect. PMID- 1294329 TI - The reactions of beta- and alpha-pyranose peracetates with PCl5, and utilization of the products to construct sarsasapogenin glycosides. AB - The reactions of beta- and alpha-pyranose peracetates with PCl5 gave products regioselectively chlorinated. The reactions of 1,2,3,4,6-penta-O-acetyl-beta-D glucopyranose (5) and -beta-D-galactopyranose (6) with PCl5 in CCl4 and that of methyl 2,3,4-tri-O-acetyl-beta-D-glucuronatopyranose (7) with PCl5 in toluene gave 2-O-trichloroacetyl-beta-D-pyranosyl chlorides 4, 12 and 14, respectively, as major products, and alpha-D-pyranosyl chlorides 11, 13 and 15, respectively, as minor products. On the other hand, the reactions of compounds 8 and 9 which were alpha-anomers of 5 and 6, respectively, with PCl5 gave as major products transformed acetyl groups at C-6 to -C(Cl) = CCl2 or -C(Cl)2-CCl3 group (16 and 17 from 8 and 18 from 9). The same reaction of 10, which was alpha-anomer of 7, gave alpha-chloride 15 as a major product. The glycosidation of sugar derivative 4 with sarsasapogenin 23 gave beta-glycoside 24 (29.1%) and alpha-glycoside 25 (46.9%), and that of 12 with 23 gave beta-glycoside 26 (24.0%) and alpha glycoside 27 (40.8%). The improvement of the yields of beta-glycosides 24 and 26 (66.9 and 62.1% for 24 and 26, respectively) in the glycosidations were accomplished by the employment of alpha-bromides 28 and 29 obtained from 4 and 6, respectively. The glycosidations of monoglycosides 30 and 31 obtained by the treatment 24 and 26, respectively, with ammonia-saturated ether with sugar acetate bromides 32 and 34 gave diglycoside derivatives 35 and 33, respectively. PMID- 1294330 TI - Six new triterpenoidal glycosides including two new sapogenols from Albizziae Cortex. V. AB - Six new triterpenoid glycosides called julibrosides A1-A4, B1 and C1 were isolated from Albizziae Cortex, the dried stem bark of Albizzia julibrissin Durazz. Their structures were determined based on spectral and chemical evidence. Julibrosides B1 and C1 had new sapogenols, designated julibrogenin B and C, respectively, while julibrosides A3 included N-acetyl-D-glucosamine as a sugar component. PMID- 1294331 TI - Isolation and identification of a cytotoxic principle from Chrysosplenium grayanum Maxim. (Saxifragaceae) and its antitumor activities. AB - A cytotoxic principle was newly isolated from Chrysosplenium grayanum Maxim. (Saxifragaceae) and identified as beta-peltoboykinolic acid (1) on the basis of spectral data. Cytotoxicity of compound 1 was tested against various human cancer cell lines in vitro, and antitumor effect of this compound was demonstrated on Meth.A mouse fibrosarcoma. The experiment of combined treatment with compound 1, mitomycin C, and OK-432 resulted in enhancing the antitumor effect against B16 BL6 mouse melanoma in C57BL/6 mice. PMID- 1294333 TI - Bioavailability study of commercial sustained-release preparations of diclofenac sodium in gastrointestinal physiology regulated-dogs. AB - The gastrointestinal (GI) physiology of beagle dogs was regulated with a combined treatment of intramuscular pentagastrin (10 micrograms/kg x 2) and intravenous atropine sulfate (0.02 mg/kg x 1). Here, the gastric acidity, the gastric emptying time and the small intestinal transit time in the regulated-dogs were respectively around pH 2, 0.7h and 4h, approximating those in healthy humans. The superiority of the regulated-dogs over the intact dogs was confirmed in comparative bioavailability studies by using two classes of commercial preparations. Both the conventional tablet and the sustained-release capsule of diclofenac sodium exhibited simple and similar average plasma concentration-time curves of free diclofenac in the intact dogs, while the latter preparation is reported to reveal a bimodal plasma curve of the drug in healthy humans. The regulated-dogs, however, permitted a bimodal average plasma pattern of the drug for the capsules due to an approximation of the GI physiology between humans and these classes of the dogs. The combined-treatment of beagle dogs with pentagastrin and atropine sulfate seems to supply a useful animal model in predicting the absorption characteristics of the sustained-release preparations and poor water-soluble drugs. PMID- 1294332 TI - Nucleotide sequences of membrane-bound hydrogenase gene in Alcaligenes hydrogenophilus. AB - The nucleotide sequences of membrane-bound hydrogenase small (hupS) and large (hupL) subunit genes of hydrogen bacterium Alcaligenes hydrogenophilus were determined. The hupS and hupL genes encoded polypeptides of 363 and 619 amino acids, respectively. The hupS was located upstream of hupL with 35bp of intergenic region. The consensus ribosome-binding sequences were identified upstream of the start codons of hupS and hupL. Amino acid sequence of hupS is very similar to that of Rhodobacter capsulatus, Bradyrhizobium japonicum, and Azotobacter vinelandii at amino acid levels of 82%, 77%, and 81%, respectively. Similarly, amino acid sequence of HupL is similar to that of R. capsulatus, B. japonicum, and A. vinelandii at amino acid levels of 63%, 65%, and 68%, respectively. Northern hybridization analysis showed that hupS and hupL were co transcribed, and addition of fructose to the culture medium remarkably decreased the amount of mRNA transcribed from hupS and hupL. PMID- 1294334 TI - Inhibition of apical membrane enzyme activities and protein synthesis by gentamicin in a kidney epithelial cell line LLC-PK1. AB - The mechanism of a gentamicin-induced decrease in apical membrane enzyme activities was investigated in LLC-PK1 cells. Increasing activities of apical membrane enzymes (alkaline phosphatase, aminopeptidase, and gamma glutamyltransferase) were markedly suppressed by gentamicin during growth in culture. On the other hand, a lesser effect was observed when the activities of these enzymes were decreasing or relatively constant. Gentamicin treatment decreased the maximal enzyme activities of alkaline phosphatase and aminopeptidase, indicating that the number of active enzyme molecules in the apical membrane was decreased by gentamicin. [3H]Leucine incorporation in LLC-PK1 cells was inhibited by gentamicin in a dose-dependent manner, followed by a reduction of total protein. In addition, a well-known protein synthesis inhibitor, cycloheximide, also decreased the apical enzyme activities. These results suggest that the inhibition of protein synthesis by gentamicin is a possible cause of the decreased activities of apical membrane enzymes in LLC-PK1 cells. The inhibition of protein synthesis may be related to the nephrotoxicity induced by aminoglycoside antibiotics. PMID- 1294335 TI - Thyroxine binding properties of glycosylated bovine serum albumin. AB - Thyroid hormone, thyroxine (T4) binding properties of glycosylated bovine serum albumin (G-BSA), and intact BSA were studied by the fluorescence method. The apparent binding constants for intact BSA were 0.8 (0.16) x 10(6) M-1 at pH 5.0 and 2.18 (0.06) x 10(6) M-1 at pH 9.5 at 25 degrees C. T4 binding for G-BSA was independent of pH and the apparent binding constant was 1.4 x 10(6) M-1. Thermodynamic parameters were also evaluated from the Van't Hoff plots of the apparent binding constants at pH 7.4 and 8.5. At both pH's, the free energy, enthalpy and entropy changes were almost the same for both G-BSA and BSA. PMID- 1294336 TI - Triterpene glycosides from the seeds of Astragalus sinicus L. AB - From the seeds of Astragalus sinicus L. (Leguminosae), seven triterpene glycosides were isolated and identified as soyasaponin I-III methyl esters (1-3) which were treated with CH2N2 during the separation procedure, soyasaponin IV (4), soyasapogenol B 3-O-beta-D-glucuronopyranoside (5), 3-O-alpha-L rhamnopyranosyl(1-->2)-beta-D-xylopyranosyl(1-->2)-beta-D- glucuronopyranosyl 3 beta, 22 beta, 24-trihydroxy-11-oxoolean-12-ene (6), whose sapogenol (8) was obtained by enzymatic hydrolysis using glycyrrhizinic acid hydrolase, unambiguously characterized and designated as complogenin, and 3-O-alpha-L rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D - glucuronopyranosyl complogenin (7). PMID- 1294337 TI - A new metabolite of 2,4,3',4'-tetrachlorobiphenyl in rat feces. AB - Metabolism in vivo of 2,4,3',4'-tetrachlorobiphenyl (TCB) was further studied using male Wistar rats. When the extract of feces of rats given TCB with chloroform was methylated and applied to gas chromatography (GC)-mass spectrometry (MS), a new metabolite was detected. The structure of this new metabolite was 4-hydroxy-2,5,3'4'-TCB based on both its retention time in GC and comparison of the mass spectrum with that of the synthetic sample. 4-Hydroxy 2,5,3',4'-TCB was assumed to be formed via a 4,5-oxide intermediate followed by NIH-shift of a chlorine atom at 4-position. PMID- 1294338 TI - Gastric emptying rate of drug preparations. III. Effects of size of enteric micro capsules with mean diameters ranging from 0.1 to 1.1 mm in man. AB - The gastric emptying rates of three enteric micro-capsule preparations with mean diameters of 1.1 mm and less (1.1, 0.5 and 0.1 mm) were compared. The gastric emptying rate was evaluated by determining the pharmacokinetic parameters of pyridoxic acid, including Vmax (peak excretion rate) and Tmax (time to reach peak excretion rate) after oral administration of micro-capsules containing pyridoxal phosphate as a marker drug to five healthy subjects. When given under fasting conditions, the gastric emptying rates of these preparations, according to Tmax, differed significantly; the preparations with smaller particle sizes were emptied from the stomach at a faster rate than those with larger particle sizes. However, under non-fasting conditions the gastric emptying rates were virtually the same, regardless of particle size, and all the preparations were emptied from the stomach at a much slower rate than when administered under fasting conditions. PMID- 1294339 TI - Tinctormine, a novel Ca2+ antagonist N-containing quinochalcone C-glycoside from Carthamus tinctorius L. PMID- 1294340 TI - Clinical and laboratory work-up prior to hormone replacement therapy in postmenopausal women. AB - In a retrospective study on 100 female patients (mean age 52 years), with a menopause lasting for 3.5 years, referred to the Menopausal Clinic of Beilinson Medical Center, we studied the pretreatment, clinical and laboratory work-up before administration of hormone replacement therapy (HRT). The work-up consisted of clinical and medical examination and history. Mammography is a necessary test for malignancy exclusion, and also the assessment of lipid metabolism. Pap smear is not so important since cervical cancer is a rare event in Jewish women and pelvic sonography cannot be a decisive diagnostic tool for ruling out malignancy. We conclude that HRT for prevention of osteoporosis and cardiovascular disease should be administered in a menopausal clinic by a gynecologist, after performing a few tests: confirmation of menopause by follicle-stimulation hormone (FSH) and E2, excluding malignancy by mammography, and confirmation of normal lipid metabolism. PMID- 1294341 TI - Iron balance in pregnancy in relation to anemia. AB - Blood levels of iron, transferrin and ferritin varied in the course of pregnancy (6th to 42nd week) in 136 women. Analysis of variance showed that the factor "weeks of pregnancy" (< or = 27 or > 27 weeks) was correlated differently with the variables "ferritin" and "iron" according to the presence or absence of anemia (Hb < or = or > or = 11 g/dl). In anemic women the correlation was significant (F-ratio = 5.90; P = 0.018) for iron (which decreased from initial low level until term) but not ferritin, whereas in non-anemic women the correlation was significant (F-ratio = 13.306; P = 0.0006) for ferritin (which decreased to less than 20 micrograms/ml around the 34th week) but not iron. In both anemic and non anemic subjects, transferrin levels increased with weeks of pregnancy. It is concluded that towards the end of pregnancy, some decrease in ferritin (> or = 15 micrograms/ml) is physiological, and in the absence of anemia (Hb > 11 g/dl) iron supplements are not necessary. PMID- 1294342 TI - Cystic hygromas associated with Turner's syndrome. Report of three cases. AB - Three cases of cystic hygromas are reported. Two of these were singleton pregnancies diagnosed at 20 weeks' gestation and the other was an affected fetus in a twin pregnancy at 19 weeks gestation. Amniocentesis was done and chromosomal analysis revealed Turner syndrome in all cases. The two singleton pregnancies were terminated by intrauterine installation of PgF2a. The affected fetus of the twin pregnancy died at 24 weeks' gestation and the pregnancy continued. PMID- 1294343 TI - Quantitative ultrasound diagnosis of endometrial cysts. AB - We measured the ultrasonic frequency dependent attenuation of ovarian cysts using the spectral difference method to find the difference in the characteristics of attenuation of the endometrial cyst and other ovarian cysts. We investigated an analytical method to measure the ultrasonic frequency dependent attenuation of ovarian cysts and we called this method the boundary echo spectrum method. The endometrial cyst had an attenuation slope of 0.67 +/- 0.27 dB/cm/MHz, and attenuation value was 1.85 +/- 1.27 dB/cm, and it had significantly higher attenuation slope and attenuation value compared with those of serous cystadenoma and mucinous cystadenoma, but no significant difference compared with those of dermoid cyst (fat component). Compared with attenuation slope and attenuation value, attenuation slope is superior because of smaller standard deviation and better linearity between water immersion and transabdominal method. PMID- 1294344 TI - Maternal fructosamine and glycosylated haemoglobin in the prediction of gestational glucose intolerance. AB - The value of maternal glycosylated haemoglobin (HBA1c) and fructosamine in the prediction of gestational diabetes is debated. One hundred high risk patients were grouped as normal, impaired glucose tolerance (IGT) and gestational diabetes mellitus, according to the WHO criteria, after 2 hours, 75 g oral glucose tolerance test (OGTT). Maternal HBA1c and fructosamine were measured at different gestational ages and at the start of labour. The aim of the study was to determine the most sensitive predictor of abnormal glucose tolerance. Maternal fructosamine was higher in gestational diabetics than in the other two groups, but the difference was not of statistical significance. The values for normal and IGT groups overlapped markedly. The fructosamine test sensitivity was 12.2%, specificity was 94.7% and predictability was 75%. Glycosylated haemoglobin was significantly higher in IGT and gestational diabetes mellitus (GDM) groups than in the normal group after 36 weeks of gestation. At 32 weeks or less the difference was not of statistical significance. As with fructosamine, there was a wide range of value that overlapped markedly, particularly between the normal and IGT patients. The HBA1c test sensitivity was 19.1%, specificity was 95% and predictability was 81.1%. This suggests that both HBA1c and fructosamine have very low sensitivity as predictors of gestational glucose intolerance. PMID- 1294345 TI - Bromocriptine (Bromergon, Lek) in the management of premenstrual syndrome. AB - The efficacy of bromocriptine (Bromergon, Lek) was studied in a group of 21 women with premenstrual syndrome (PMS). To qualify for inclusion, the patients had to have a score of 20 or more on Casper's Analog Self-Rating Scale for Premenstrual Tension Syndrome completed during the last premenstrual week. The study was designed as a double-blind, randomized, cross-over trial introduced by a wash-out cycle. Patients received Bromergon in a daily dose of 5 mg from cycle day 10 to the onset of menstruation for two consecutive menstrual cycles, followed by two placebo cycles or vice versa. The subjects were instructed to complete the scale every three days from cycle day 3 to the onset of menstruation. A statistically significant improvement due to the administration of Bromergon was observed in symptoms associated with overreactiveness to normal prolactin levels, i.e. abdominal tension, edema, weight gain and breast tenderness. Scores on the linear analog scale and physician's assessments differed regarding psychological symptoms. The investigators observed no difference in the presence of psychic symptoms in the treatment-free period, on Bromergon therapy and during the administration of placebo. On the other hand, self-rating scores reflected an improvement in the presence of depression and irritability during Bromergon treatment. The results obtained suggest that Bromergon may be a useful agent for the treatment of somatic symptoms associated with PMS, while it seems somewhat less effective in PMS cases where psychic symptoms are the major complaint. PMID- 1294346 TI - Decrease of cellular growth potential in "in vitro" culture of amnions with premature rupture of membranes. AB - The "in vitro" cellular growth of 8 amniotic membranes from preterm deliveries with premature rupture of membrane (PROM) in absence of risk factors as cervical or vaginal infection (microbiologic negativity), cervical incontinence and other mechanical factors, was compared with cellular growth of 9 amnions from preterm deliveries without PROM. Amniotic membranes were set up in the Eagle basal medium with Earle salts and heat-inactivated fetal bovine serum (10%), gentamicin 50 micrograms/ml and amphotericin B 0.5 micrograms/ml. The results suggested that the growth potential of the cells (epithelial cells and fibroblasts) obtained from amnions with PROM was lower than that of cells obtained from amnions without PROM. We postulated that the premature rupture of membranes in patients without risk factors for PROM, would be conditioned by an intrinsic decrease of cellular growth potential. PMID- 1294347 TI - Neonatal complications and risk of intraventricular-periventricular hemorrhage. AB - We have prospectively studied 117 premature infants < or = 1500 gm (VLBW) to assess the relationship between maternal, obstetric, fetal and newborn complications and the grade of periventricular-intraventricular hemorrhage (PVH IVH). PVH-IVH was documented by cranial ultrasonography in 41% of surviving neonates. 83% of infants with PVH-IVH grade I-II survived as compared to the 39% of infants with PVH-IVH grade III-IV (p < .001). Maternal and obstetric complications were not associated with PVH-IVH (NS). Newborn respiratory complications (p < .004) and major infections (p < .02) are independent variables associated with PVH-IVH. Immaturity at delivery, metabolic acidosis, respiratory distress syndrome and recurrent apnea are important mechanisms of cerebral injury contributing to severity of PVH-IVH. PMID- 1294348 TI - Breech presentation: obstetrical risks. Data from the Bavarian Perinatal Evaluation (BPE). PMID- 1294349 TI - Caesarean section and breech delivery. Old question--new answers. PMID- 1294350 TI - Shoulder dystocia: revisited. PMID- 1294351 TI - Mayer-Rokitansky-Kuster Syndrome: Vecchietti's personal series. PMID- 1294352 TI - Diagnostic and therapeutic hysteroscopy. PMID- 1294353 TI - Operative hysteroscopy. PMID- 1294354 TI - Microcarcinoma of the cervix: diagnosis and treatment. PMID- 1294355 TI - Personal experiences with exenterations in patients with gynecologic malignancies. PMID- 1294356 TI - The value of pelvic lymphadenectomy in endometrial cancer. PMID- 1294357 TI - Surgical strategies in vulvar cancer. PMID- 1294358 TI - Circulating low molecular weight IgM--a disease marker in autoimmune, infective, immunodeficient and B cell lymphoproliferative disorders. PMID- 1294359 TI - Clinico-immunogenetic study on Egyptian multicase tuberculous families. AB - Thirteen multicase Egyptian families (having more than one sib affected) with pulmonary tuberculosis have been studied. They include 26 parents (4 were tuberculous) and 53 sibs (30 tuberculous and 23 healthy). For all of them the following have been carried out: (a) Clinical, radiological, and bacteriological examination for diagnosis and evaluation of the disease severity; HLA-antigen determination using 9(A), 16(B) and 6(DR) antigens. The analysis of data revealed: (1) high incidence of tuberculosis among sibs in families having A2 B5 in their haplotypes compared to those having A2 X or B5 X--affected sibs with A2 B5 showed more severe manifestations than those having only one of the two antigens; (2) aggregation of HLA concordance among the sib pairs, both fully identical and haploidentical, while none of the sib pairs is non-identical; (3) Lod score studies showed linkage between the genetic control of susceptibility to pulmonary tuberculosis and HLA; (4) identity by descent study confirms the dominant pattern of transmission. The recommendation is that in a clinical setting of genetic counselling healthy individuals having either A2 or B5 antigens in their haplotypes should be vaccinated with BCG. Furthermore tuberculous patients having these HLA antigens should be managed aggressively, especially those having A2 B5 haplotypes in whom the disease is likely to run a severe course. PMID- 1294361 TI - Lack of in vivo transcription of Acetabularia mediterranea 1175 bp ctDNA fragment homologous to the Drosophila per locus. AB - The period (per) locus of Drosophila melanogaster has a fundamental role in the expression of biological rhythms. A DNA sequence homologous to a short region of the Drosophila per locus was detected in the chloroplast of Acetabularia mediterranea. A 1175 bp DNA fragment containing the sequence was used as a probe in 'Northern' hybridization experiments. It was found that this DNA was not transcribed or only marginally transcribed in A. mediterranea, at least at the developmental stage just prior to cap formation. It seems that the 1175 bp ctDNA fragment is not involved in the Acetabularia biological rhythm mechanism. PMID- 1294360 TI - Lack of association of the alpha-1-antitrypsin PIZ allele with rheumatoid arthritis or with its extra articular complications. AB - PIZ allele frequencies were defined by PCR amplification and hybridization using a PIZ SSO (sequence specific oligonucleotide) probe. The groups studied included 64 normal controls, 104 subjects with rheumatoid arthritis (RA) without any extra articular features, 29 of whom had severe arthritis and 31 of whom had mild RA. The extra-articular subsets include 41 with RA-bronchiectasis (RA-BR), 21 with bronchiectasis without RA (BR), and 23 with RA and pulmonary fibrosis (RA-PF). Fifteen RA subjects with obstructive airways disease (RA-OAD) were compared to 25 RA patients with normal lung function tests. Using Fishers' exact test and chi squared statistical analysis with Yates correction, no statistically significant associations were found between PIZ and any of the groups studied. Thus in this population there is no evidence that PIZ either increases susceptibility to rheumatoid arthritis or affects the risk of pulmonary complications or the severity of arthritis in subjects with rheumatoid arthritis. PMID- 1294362 TI - Effects of calcitonin and calcitonin gene-related peptide on 3H-thymidine incorporation into DNA of rat thyroid lobes in vitro. AB - The effects of a 4 h incubation of rat thyroid lobes, in the presence of calcitonin (CT) and calcitonin gene-related peptide (CGRP) on the incorporation of 3H-thymidine into DNA, were investigated. In other groups the thyroid lobes were incubated during exposure to CT and thyrotropin (TSH), and to CGRP together with TSH. All concentrations of CT (10(-6)-10(-8) M) revealed a tendency towards lowering 3H-thymidine uptake, but the effect was not statistically significant. The influence of CGRP was dose-dependent; the lowest concentration of CGRP (10( 9) M) significantly enhanced DNA synthesis in the incubated rat thyroids; an intermediate dose of the peptide (10(-8) M) had no effect, while the highest concentration of CGRP (10(-7) M) decreased 3H-thymidine incorporation. Calcitonin (10(-7) M), as well as CGRP (10(-8) M), suppressed the stimulatory effect of TSH on 3H-thymidine incorporation. PMID- 1294363 TI - Effect of fasting, branched-chain amino acids, and glucocorticoids on histone H1 extractability from rat skeletal muscle. AB - The effect of 72 h fasting, nutritional therapy of fasted rats, and acute and chronic glucocorticoid treatment on the yield of histone H1 from rat hind limb muscles was determined. Fasting significantly enhanced the extractability of muscle H1. The effect of treating starved rats with glucose alone, or with glucose supplemented with branched-chain amino acids (BCAA), or with two commercial preparations of mixtures of essential and non-essential amino acids was evaluated. Treatment of starved rats with glucose alone significantly decreased H1 extractability from muscles, but isocaloric treatment with glucose supplemented with BCAA or two commercial preparations of amino acid mixtures was more effective. Glucocorticoid treatment for 5 days enhanced the yield of H1 from muscles less than starvation. The enhanced H1 extractability from muscles noted in starved rats is similar to that reported in rats with insulinopenic diabetes and may reflect changes in nuclear fragility. PMID- 1294364 TI - Child abuse and neglect fact sheet. PMID- 1294365 TI - Improving child protective services: how to expand and implement the consensus. PMID- 1294366 TI - Healthy families America. PMID- 1294367 TI - Shaken baby syndrome. The problem and a model for prevention. PMID- 1294368 TI - The secretary's initiative on child abuse and neglect. PMID- 1294369 TI - [Diagnosis and therapy of pleural empyema. 7th trilateral symposium of thoracic surgery. Bad Schandau, 15-17 May 1992]. PMID- 1294370 TI - Relationship between inhibitor of extrathyroidal 5'-deiodinase activity and serum free fatty acid in children with nonthyroidal illness and acute ketosis. AB - To clarify whether serum free fatty acid (FFA) is an inhibitor of extrathyroidal conversion (IEC) of thyroxine (T4) to thyronine (T3), we measured the concentration of FFA, IEC activity and thyroid hormones in normal subjects, acute ketotic children and children with low T3 syndrome due to nonthyroidal illness (NTI). Iodothyronine (I) 5'-deiodinase activity was assayed with reverse triiodothyronine (rT3) as substrate and liberated 125I-was measured. The IEC was determined by the inhibition of I 5'-deiodination by ether extract of sera or standard oleate solution. IEC values were represented as mM oleate. The serum concentration of FFA was 0.470 +/- 0.117 (SD) mM in 11 normal subjects, and it was significantly higher (1.242 +/- 0.248 mM; P < 0.01) in 10 acute ketotic children and in 7 samples from 6 NTI children (0.904 +/- 0.530 mM; P < 0.05). In contrast, there was no difference in IEC among three groups (normal subject, 0.451 +/- 0.069 mM; acute ketosis, 0.437 +/- 0.040 mM; NTI, 0.465 +/- 0.224 mM). No correlations were found between IEC activity and the serum FFA concentration or thyroid hormones in 28 samples from three groups. The sequential changes in serum thyroid hormones, FFA and IEC in 3 of 6 NTI children revealed no consistent relationship. Furthermore, one NTI child had significantly high IEC (> 1.000 mM) but its serum FFA (1.182 mM) was below the mean value for the acute ketotic group. These results indicate that 1) many NTI patients may bear no relation to IEC and 2) IEC may not be caused by serum FFA only but includes several factors. PMID- 1294371 TI - Generalized resistance to thyroid hormone (GRTH) in a family: case studies. AB - A familial case of generalized resistance to thyroid hormone (GRTH) is described. A 17-year-old man (case 1), who had been treated with methimazole under the diagnosis of Graves' disease and his 11-year old sister (case 2) visited our clinic for the evaluation of their thyroid function. They lacked the signs and symptoms of thyrotoxicosis in spite of extremely high serum thyroid hormone levels. Their plasma TSH levels were not suppressed, but in fact markedly increased after TRH loading. Their peripheral indices of thyroid hormone were within normal limits and were not influenced by exogenous T3 administration. Even 150 micrograms T3 administration for 7 days did not fully suppress the TRH stimulated TSH level in case 2. The two patients thus were diagnosed to have GRTH. Sera from their father and another sister showed identical abnormalities. PMID- 1294372 TI - The effect of DHAS on steroidogenesis of the human corpus luteum. AB - To examine whether or not dehydroepiandrosterone sulfate (DHAS) is a substrate for steroidogenesis in the corpus luteum, we studied 17 women in the luteal phase, the follicular phase, and after castration. Following suppression of adrenal function with dexamethasone, DHAS was administered intravenously and the serum levels of DHAS, dehydroepiandrosterone (DHA), androstenedione (ADS), testosterone (T), 17 beta-estradiol (E2) and progesterone (P) were measured serially for 24 h. An obvious increase in the serum levels of all steroids except for E2 and P was observed in each subject for at least 8 h after DHAS administration. To evaluate the effect of DHAS on the serum levels of the steroid hormones, the integrated response area (IRA) was calculated for each hormone in all the subjects. The IRA values for ADS, T and E2 (at 2 and 4 h) in the luteal phase group were significantly higher than in the other DHAS treated groups, and the IRA values for DHA and P tended to be higher than in the other groups. These results suggest that the corpus luteum utilizes serum DHAS as a substrate for steroidogenesis. PMID- 1294373 TI - Characterization of parathyroid hormone-related protein in the human term placenta. AB - To characterize parathyroid hormone-related protein (PTHrP) in the human placenta, we measured PTHrP-like immunoreactivity (PRP-LI) in the term placenta and studied the elution profiles of placental tissue extracts on Sephadex G-75 chromatography with a specific RIA. We also examined the gene expression of PTHrP mRNA by Northern blot analysis and the localization of PRP-LI in the placenta by immunohistochemistry. The amount of PRP-LI in placental extracts (n = 7) was 20.9 +/- 2.2 pg/g wet tissue (mean +/- SE). Dilution curves of placental tissue ran parallel to those of synthetic PTHrP (1-34) standards. Sephadex G-75 gel chromatography demonstrated two major PRP-LI peaks; the first peak was eluted around the molecular size between 10 kilodaltons (Kda) and 20 Kda and the other around 5 Kda. Northern blot analysis of PTHrP mRNA extracted from placental tissues showed a major hybridization signal around 18S. PTHrP immunohistochemistry showed PRP-LI staining in the cytoplasm of syncytiotrophoblasts and stroma cells (Hofbauer cells) in the term placenta. These results suggest that syncytiotrophoblasts and stroma cells in the term placenta synthesize PTHrP in two major molecular forms, 10 Kda-20 Kda and around 5 Kda. PMID- 1294374 TI - Clinical significance of adrenal computed tomography in Addison's disease. AB - Adrenal computed tomographic (CT) scanning was conducted in twelve patients with Addison's disease during the clinical course. In tuberculous Addison's disease (n = 8), three of four patients examined during the first two years after disease onset had bilaterally enlarged adrenals, while one of four had a unilaterally enlarged one. At least one adrenal gland was enlarged after onset in all six patients examined during the first four years. Thereafter, the adrenal glands may atrophy bilaterally, in contrast to adrenal glands in idiopathic Addison's disease, which atrophy bilaterally from disease onset (n = 2). Adrenal calcification was a less sensitive clue in tracing pathogenesis, i.e., adrenal calcification was observed in five of eight patients with tuberculous Addison's disease, but not in idiopathic patients. Thus, adrenal CT scanning could show the etiology of Addison's disease (infection or autoimmunity) and the phase of Addison's disease secondary to tuberculosis, which may be clinically important for initiating antituberculous treatment. PMID- 1294375 TI - Transient extreme insulin resistance in shock during diabetic ketoacidosis. AB - Transient extreme insulin resistance was encountered during an episode of diabetic ketoacidosis (DKA) in an insulin-treated diabetic patient. On admission, the plasma glucose level was 1241 mg dl-1 and arterial blood pH 6.895 with HCO3- 4.7 mEql-1. An intravenous bolus injection of 20 units, followed by continuous infusion of 20 units h-1 of short-acting regular human insulin, was instituted. Ischemic myocardial changes were noted on the initial electrocardiogram, therefore fluid replacement was limited to 1,000 ml of 0.9% saline solution in the first hour. As the plasma glucose level declined by only 203 mg dl-1 (41 mg dl-1 h-1) in the first 5 h, the insulin dose was doubled every 2 h. At hour 4, the patient developed circulatory shock which required vasopressor support and respiratory assistance. A plasma glucose level of 300 mg dl-1 was not achieved until the total dosage of insulin amounted to 91,580 units at hour 25. Insulin resistance was not observed from that point on. The patient had neither insulin antibodies nor anti-insulin receptor antibodies in serologic testing. The insulin binding characteristics of the patient's erythrocytes were similar to those from healthy controls both with and without experimental acidosis and with a high level of beta-hydroxybutyrate. Among multiple potential factors, the severe shock associated with DKA has been considered as a primary cause of the transient severe insulin resistance in this case. PMID- 1294376 TI - Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family. AB - Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein. Several inherited TBG variants resulting in partial or complete TBG deficiencies have been shown to be caused by either one or two nucleotide substitutions, or one nucleotide deletion in the coding regions of the TBG gene. In this report, a Japanese female patient (proband) with hyperthyroid state, whose lower TBG levels did not return to normal under the euthyroid state after treatment was examined. Genomic DNA samples from the proband with thyroxine-binding globulin deficiency (termed TBG-Kumamoto) and her family were subjected to the polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide substitution in the codon for the amino acid 363 of native TBG molecule (CCT to CTT) was found, resulting in the replacement of proline by leucine. It was revealed that the proband was a heterozygote and her father was a hemizygote. The mutation was confirmed by the allele-specific amplification of genomic DNAs from the proband and her father using oligonucleotide primers of normal or mutant residues at the 3' position in the polymerase chain reaction. These results indicate that the abnormality of TBG-Kumamoto is the consequence of this mutation. Genetically, this point mutation observed in TBG-Kumamoto might be classified as a new type of TBG deficiency. PMID- 1294378 TI - Immunohistochemical evidence that rat FSH cells contain beta II-subspecies of protein kinase C. AB - Immunocytochemical double-staining analysis revealed that in the rat anterior pituitary 86% of cells containing the beta II-subspecies of protein kinase C also contained follicle stimulating hormone (FSH), and that 22% of these FSH cells expressed the beta II-subspecies. These findings suggest a close relationship between the beta II-subspecies of protein kinase C and FSH regulation. PMID- 1294377 TI - Source of prolactin in human follicular fluid. AB - To analyze whether prolactin (PRL) in human follicular fluid (FF) is synthesized locally or derived from the circulation, PRL concentrations of plasma and FF were determined in the patients after ovarian stimulations. The amounts of PRL messenger ribonucleic acid (mRNA) in the follicular tissues during different menstrual phases were also determined. The FF PRL concentration was correlated positively with plasma PRL and highest estradiol levels during the stimulatory cycle. No PRL mRNA sequence was detected in the RNAs extracted from follicles at any stage in the menstrual cycle, although beta-actin mRNA was detected in all samples. In a comparison with pituitary RNA, the PRL mRNA concentration in ovarian follicular tissues seemed to be 10,000 times less than that in the pituitary. These results suggest that FF PRL may not be synthesized locally, but derived from the pituitary via the circulation through passive diffusion, and thus regulated by estrogen. PMID- 1294379 TI - The relationship between education and risk factors for coronary heart disease. Epidemiological analysis from the nine communities study. The Research Group ATS OB43 of CNR. AB - In nine samples of adult populations (2707 males and 2871 females, aged 20-59 years) we studied the relationship between educational level and several lifestyle factors at risk for coronary heart disease (CHD), (i.e., smoking, alcohol consumption, dietary fat intake, sedentary behaviour at work and leisure) and the association between education and certain CHD risk factors (i.e., total cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressure, body mass index). The data were analyzed separately in samples from North, Central and Southern Italy. The results show that educational level is often associated to the lifestyle factors considered here. This association was positive for both men and women for physical activity at leisure and work stress and only for women with respect to smoking. It was negative for both men and women for alcohol consumption and physical activity at work and for men only for cigarette smoking. The age-adjusted mean levels of the CHD risk factors show some significant differences among subjects with different educational levels, which were not always the same for the three geographical areas. This was with the exception of BMI in females, which appears negatively associated to education in all areas. These differences decreased after adjustments were made for daily cigarette smoking, wine consumption and dietary fat intake. Education seems to play a determining role in lifestyle, however, its direct and indirect effects on some major CHD risk factors are somewhat different in areas at different socio economic conditions. PMID- 1294381 TI - The independent effect of habitual cigarette and coffee consumption on blood pressure. AB - The authors investigated the possible relation between habitual cigarette and coffee consumption and blood pressure (BP) levels in 7506 men and 2095 women. The study population were managers and employees examined in northern Italy between 1986-1988. In particular, the hypothesis of a substantial independence between smoking-BP and coffee-BP was tested. BP levels were corrected for age, body mass index, physical activity, and alcohol consumption by analysis of covariance. Significantly, smoking was inversely related to BP, both in men (SBP, P < 0.001, DBP, P < 0.001) and women (SBP, P = 0.001, DBP, P = 0.012). In particular, the BP of non-smoking men, SBP/DBP, was 131.0/83.5, whereas in male smokers up to and over 20 cigarette/day, BP was 128.1/82.0 and 128.1/82.1 respectively. Coffee consumption was related to BP levels in men (SBP, P < 0.001; DBP, P = 0.009), but not in women (SBP, P = 0.320; DBP, P = 0.982). BP in male subjects was 131.3/83.5 in non-drinkers, 130.7/83.3 in those drinking 1-3 cups/day, 128.4/82.6 and 127.2/81.8 in drinkers of 4-5 and over 5 cups/day, respectively. No significant interactions were demonstrated, thus the relationship between habitual smoking and coffee consumption with BP appears to agree with an additive model. PMID- 1294380 TI - Correlation between mortality trends of ischaemic cardiopathy and some nutritional factors in Spain 1968-1986. AB - After describing the evolution of mortality from ischaemic cardiopathy (IC) in Spain from 1951 to 1986, which is tending to stabilize in some age groups, and from cerebrovascular accidents (CVA), which is clearly declining, an attempt is made to relate these developments to the prevalence of the main risk factors (hypertension, cholesterol, tobacco) associated with IC and CVA. Certain advances, though of a limited number, have been made in recent years in the control of arterial hypertension in Spain, although campaigns on a national scale as in other countries have not been carried out. Regarding alimentary factors, there is an obvious increase in the consumption of food rich in proteins and animal fats, abandoning to a great extent the traditional "Mediterranean diet", with health care action being limited to the improvement of nutrition education of the public. Furthermore, the consumption of tobacco has been increasing in Spain during the study period in spite of health legislation in force in recent years. It is therefore deduced that there is no obvious relationship between mortality due to IC and CVA and the prevalence of the main risk factors associated with these diseases, especially when taking into account that preventive actions on a public health level have been very limited. PMID- 1294382 TI - Cardiovascular risk factors and prevalence of coronary heart disease in type 2 (non-insulin-dependent) diabetes. AB - The relationship between cardiovascular risk factors and the prevalence of coronary heart disease was examined in 152 Type 2 diabetic patients (65 men, 87 women) aged 35-54 years and in 105 randomly selected control subjects (46 men, 59 women). Coronary heart disease, defined by symptoms and ECG abnormalities, was 1.2 times higher in male and 3.4 times higher in female diabetic patients than in the controls. In logistic regression analysis (including diabetes, age, body mass index, triglycerides, HDL-cholesterol, non-HDL-cholesterol and hypertension) diabetes showed an independent, significant association to coronary heart disease in women, whereas hypertension was independently related to coronary heart disease in men. PMID- 1294383 TI - A case-control study of major congenital heart defects in Sweden--1981-1986. AB - This paper reports the results of a case-control study of major congenital heart defects (CHD) in Sweden. During the period 1981-1986, 1,324 such cases were identified and 2,648 controls were selected. Some common maternal characteristics and exposures were studied using information from prospectively collected data. Possible associations with CHD were found for previous perinatal death, maternal diabetes, epilepsy, hydramnios and disproportion between fetus and pelvis. More specific associations were observed between previous spontaneous abortion, epilepsy, hydramnios and truncus anomalies and between diabetes and septal anomalies. However, no associations were found with involuntary childlessness, contraceptive use, or smoking. PMID- 1294384 TI - An epidemiologic study of environmental and genetic factors in congenital hydrocephalus. AB - Risk factors were studied in 96 children with congenital hydrocephalus (CH) coming from 118,265 consecutive births of known outcome. Hydrocephalus with neural tube defects, intracranial tumors or secondary to brain atrophy were excluded. The prevalence of CH was 0.81 per thousand. Diagnosis was performed prenatally in 41 cases. Forty-three (44.8%) of the cases had hydrocephalus without other malformations (isolated hydrocephalus), 18 (18.7%) infants had recognized chromosomal or non-chromosomal syndromes and 35 children (36.4%) had multiple malformations. Each case was matched to a control. Weight and length at birth of children with hydrocephalus were less than in the controls (p < 0.001). The weight of the placenta was lower than in the controls (p < 0.05). The pregnancy with a hydrocephalic child was more often complicated by threatened abortion, polyhydramnios and oligohydramnios. The mothers of children with hydrocephalus and multiple malformations had used oral contraceptives during the first trimester of pregnancy more often than the mothers of the controls. No differences appeared between the mothers of children with CH and the controls for the other risk factors studied: parental age, parity, previous pregnancies, previous stillbirths, smoking, diabetes, epilepsy, X-rays, hypertension, fever "flu", medication and occupational exposure. There was an increase of parental consanguinity in the parents of our patients (6.2% v. 1.1%, p < 0.001) and first degree relatives had more non-cerebral malformations than the controls (7.3% v. 3.2%, p < 0.05). PMID- 1294385 TI - Are homes for the elderly still a risk area for HBV infection? AB - To verify whether improvements in hygiene affect the risk of HBV infection, a seroepidemiological survey on HBV infection was carried out in a home for the elderly with continuous-care accommodation. HBV serum markers were tested in 315 subjects and the results of HBV infection were compared to those observed in two different types of nursing homes for the elderly from an earlier seroepidemiological study carried out in 1978. In addition, results from a cohort of a pre-geriatric population living in their own homes in the same geographical area surveyed in 1980 were compared to the present study. A statistically significant lower prevalence of HBV serum markers in the new home for the elderly compared to the two types studied in 1978 was observed. No difference was found between the new institutionalized study group and the cohort of a pre-geriatric population surveyed in 1980. These results reflect the improved sanitation in homes for the elderly and show that the elderly have very few opportunities to become infected, even in a close cohabitation system. PMID- 1294386 TI - Knowledge, attitudes and practices of Greek health professionals, in relation to AIDS. AB - In order to improve educational programmes directed at health care workers we investigated their knowledge, attitudes and practices in relation to HIV/AIDS. An anonymous self-administered questionnaires was distributed to 609 health care workers. Of these, 59.6% agreed to participate (42.4% of the medical doctors, 74.3% of the nurses and 79.6% of the laboratory technicians, health visitors and other health care workers). All studied groups believed that their knowledge of HIV modes of transmission (84.3%) was sufficient. In contrast, a relatively small percentage reported knowledge of the clinical spectrum of HIV infection (48.8%) and the diagnostic assays (57.6%). Nearly all the study participants believe (92.8%) that there is a risk of acquiring HIV infection during the hospitalization of HIV/AIDS patients. Obligatory screening of all patients was reported by nearly all participants (90.6%) as a chance to minimize their occupational risk. Although health care workers reported satisfactory knowledge of safety measures (87.0%), only 56.7% used gloves and 38.8% accept the hospitalization of HIV/AIDS patients. In spite of the educational programmes for AIDS in Greece, this study demonstrates that health professionals' knowledge and precautionary measures are not sufficient. As a result, a small percentage of them treat AIDS patients without discrimination. There is an urgent need to implement specific educational programmes for health professionals so that they will safely provide high quality care to people affected by HIV/AIDS. PMID- 1294388 TI - The epidemiology of head injury in Cantabria. AB - The epidemiology of head injury was studied in Cantabria, Spain, using a methodological design consisting of a cross-selectional analysis of one year of duration and an additional one year follow-up of all the patients included in the initial sample. The 477 cases identified represent a rate of 91/100,000, with males showing a head injury rate 2.7 times higher that than for females. Sixty per cent of all cases involved traffic accidents, falls accounted for 24% and industrial accidents were the cause in 8%. The annual age-adjusted mortality rate was 19.7/100,000. Over 92% of all deaths occurred prior to hospital admission. The presence of alcohol intoxication was evaluated in 211 cases by determining the osmolar gap. It was found that 51% of all the cases examined presented clear evidence of acute alcohol intoxication. PMID- 1294387 TI - Head injuries after serious bicycle accidents. AB - Between 1987 and 1988 there were 47 serious or fatal injuries among bicycle riders in the city of Tel Aviv-Yafo (Serious injury was defined as being hospitalized for at least 24 hours). Collisions with vehicles, mostly cars, were responsible for about 80% of these cases. Two-thirds of the accidents occurred in adults aged 20 and over. We were able to trace the records of 24 of the 47 who were injured. Head trauma was the most common form of severe injury, occurring in 11 of the 24 cases. Two of the 11 died instantly and one died after 14 days of hospitalization, all from severe brain damage. Eight suffered severe head trauma, 7 of which had brain injury and 2 of the 7 were left with severe residual brain damage. In view of the efficacy of bicycle helmets in preventing head trauma there is a great need to expand their use among bicyclists in Israel. PMID- 1294389 TI - Non-melanoma skin cancer: an evaluation of risk in terms of ultraviolet exposure. AB - A retrospective study of 143 patients histologically diagnosed with non-melanoma skin cancer (NMSC) was carried out in order to evaluate the influence of ultraviolet (UV) radiation on the appearance of more than one NMSC in the same person. Descriptive statistical and logistic regression analyses were carried out for each variable and its possible interaction, in order to determine the potential appearance of multiple NMSC. The results obtained were in agreement with those of earlier studies. A significant relationship was observed between occupational UV exposure and individuals with more than one NMSC. Those patients tended to be blue-eyed and were chronically exposed to UV radiation as a result of occupational activities (although not always in leisure activities); most did not take protective measures such as the use of hats or creams. PMID- 1294390 TI - Occupational physical activity and colon cancer risk in Turkey. AB - A case-control study of 107 colon cancer cases and 486 controls from an oncological clinic in Istanbul was conducted to examine the association between occupational physical activity and colon cancer in Turkey, where incidence of this disease is low. Only two of the four activity measures showed evidence of an increased colon cancer risk for sedentary jobs (time spent sitting OR = 1.5 and occupational energy expenditure OR = 1.6); neither was statistically significant. Subjects below age 55 showed higher risk associated with sedentary jobs than did the older age group, probably due to their adoption of a more western lifestyle, including dietary habits, less activity, and other factors that may interact to increase the risk of colon cancer. PMID- 1294391 TI - Epizootics of Salmonella infection in poultry may be the result of modern selective breeding practices. AB - This paper discusses the hypothesis that a major factor in the epizootics of Salmonella infection in poultry is a declining host genetic diversity. A computer model is described which is based on models that have been previously used to investigate host-pathogen coevolution in cereal crops. It is shown that, as host genetic diversity declines, parasite diversity also declines to a lower equilibrium level. With a highly diverse host, parasite numbers decline to zero. With a homogeneous host population, after an initial decline, there is a rapid increase in parasite numbers, due to the selection of a particularly well adapted parasite strain. This simple computer simulation is used as the basis for a discussion of the literature supporting the suggestion that a major factor in the epizootic of Salmonella in poultry is related to the low genetic diversity of commercial poultry flocks. PMID- 1294392 TI - Features of cholera and Vibrio parahaemolyticus diarrhoea endemicity in Calabar, Nigeria. AB - The clinical and epidemiological features of acute vibrio diarrhoeal disease were studied in 881 patients seen at the University of Calabar Teaching Hospital (UCTH), Calabar, Nigeria, between January and December 1989. Stools and rectal swabs of patients and randomly-selected control subjects were microscopically and culturally examined for the presence of enteric pathogens. Households of vibrio diarrhoea cases and matched controls were visited for ecologic studies. Of a total of 108 (12.3%) culturally-confirmed bacterial diarrhoeas, 47 (43.5%) were due to Escherichia coli, 33 (30.6%) to Vibrio cholerae-01 (classical and El Tor biotypes) and V. parahaemolyticus, while shigellae and salmonellae accounted for 29 (26.9%) and 9 (8.3%) cases, respectively. Most cholera case households clustered within the ancient neighbourhood of the inner city, characterized by poorly developed water and sewage disposal systems. A preponderance of vibrio diarrhoea patients were children < or = 10 years. Adult cases involved mostly females. The only case of diarrhoea-related death involved an eight-month old child with kwashiorkor and V. parahaemolyticus infection. Incidence of vibrio diarrhoeas was seasonal, with most cases occurring during the dry season followed by subsidence at the onset of rainy season. Bimodal peaks of vibrio diarrhoeal episodes observed over the period appeared to coincide with periods of acute water scarcity, high temperature, increased fishing activities and trade traffic on the Calabar River estuary. Of the environments sampled, only clam shells from a case household and river sediments yielded vibrio pathogens on culture. Ecological factors that are capable of stabilizing a focus of vibrio diarrhoea endemicity in this area are highlighted. PMID- 1294393 TI - A survey of urease-positive Vibrio parahaemolyticus strains isolated from traveller's diarrhea, sea water and imported frozen sea foods. AB - The frequency of urease-positive Vibrio parahaemolyticus among isolates from patients, imported frozen sea foods and the environment (sea water) was studied. The highest isolation frequency of urease-positive V. parahaemolyticus was found in clinical isolates (11.2% out of 204 strains examined). Urease-positive V. parahaemolyticus was found in 5.7% of 88 frozen sea food-isolates examined, but no strains isolated from sea water were urease-positive. The isolates were further examined for the production of thermostable direct hemolysin (Vp-TDH) and its related hemolysin (Vp-TRH). Both are possible pathogenic toxins produced by mostly clinical isolates of V. parahaemolyticus. Urease-positive strains have a tendency to associate with clinical isolates producing both or neither Vp-TDH and Vp-TRH. Rabbit ligated ileal loops test was performed with several strains of urease-positive and -negative clinical isolates, and we found that some strains producing urease, even those which do not produce Vp-TDH or Vp-TRH, caused intestinal fluid accumulation. PMID- 1294394 TI - Diversity of resistance phenotypes and plasmid analysis in multi-resistant 0:12 Pseudomonas aeruginosa. AB - Antibiotic resistance phenotypes, plasmid content and ability of conjugal transfer of antibiotic resistance genes of 35 multi-resistant Pseudomonas aeruginosa strains were examined. The strains were isolated in 12 Greek hospitals and the majority of them (80%) belonged to serotype 0:12. The isolates were distributed to a variety of different antibiotic resistance phenotypes. Plasmid analysis showed that 10 isolates harboured plasmids ranging in size from 20 to 100 Mda. Among these strains, four carried plasmids of 100 Mda, two strains had 60 Mda plasmid each while in three strains the plasmids detected were 65, 25 and 20 Mda, respectively. One strain harboured two plasmids of 100 and 60 Mda. All strains containing plasmids belonged to 0:12 serotype, except the one harbouring the 25 Mda plasmid, which belonged to serotype 0:6. Using a P. aeruginosa recipient resistant to rifampicin and ciprofloxacin, conjugal transfer was achieved in two occasions. These plasmids, 100 Mda in size, encoded high-level resistance to both gentamicin and tobramycin whereas resistance to other drugs was not transferable. Interestingly, all 100 Mda plasmids, including the self transferable ones, were found to share a certain degree of homology as judged by restriction analysis. It is suggested that both resistance phenotypes and analysis of plasmid content might be useful in subdividing 0:12 multi-resistant P. aeruginosa. PMID- 1294395 TI - Case-control study of congenital malformations. AB - To determine potentially teratogenic influences in Belgrade, a group of 113 mothers who gave birth to severely malformed infants and a control group of 195 mothers with normal infants were interviewed using a structured questionnaire. Statistically significant differences between the two groups were found in the mother's family history of congenital malformations (P < 0.05) and the mother's diseases during the pregnancy (P < 0.01). Infections in the first trimester were particularly more prevalent in case mothers (OR = 7.70; P < 0.01). Mothers did not differ significantly according to exposure to organic solvents, supportive therapy during the pregnancy, use of oral contraceptives, or other personal habits. PMID- 1294396 TI - Influence of different upper age limits on the "Years of Potential Life Lost" index. AB - The use of 65, 70 or 75 years as upper age limits for the "Years of Potential Life Lost" index (YPLL) could influence the relative importance assigned to different causes of premature death. Data from a representative year (1987) in Catalonia (Spain), show that health priorities and comparability among studies are not affected by the use of these upper age limits. PMID- 1294398 TI - IgA antichlamydia antibodies as a diagnostic tool for monitoring of active chlamydial infection. AB - Chlamydia trachomatis isolation in culture is the best means of chlamydial infection diagnosis. Antichlamydial antibodies, if present, may also serve as diagnostic markers. In eleven patients with positive C. trachomatis culture and serological positive response, specific IgA and IgG antibody titers were measured before and after treatment. In all cases, cultures became negative after treatment and IgA titers decreased rapidly, while IgG levels remained high. Thus, presence of specific IgA antibodies in a single sample may serve as a diagnostic tool for monitoring of active chlamydial infection. PMID- 1294397 TI - Low risk of mother to infant transmission of hepatitis B virus in Guipuzcoa (Basque country, northern Spain). AB - The prevalence of HBsAg carriers in 18,196 pregnant women (64% of women who gave birth in Guipuzcoa in 1986-1991) was 0.61% (0.43% for the last two years of the study). Three of the carriers were also HBeAg/HBV-DNA positive and two were anti HDV positive. Anti-HBc prevalence was 6.5% in 602 20-40 year old women and 1.6% in 428 girls 10-11 years old (0.47% of gypsy ethnic subjects are not included). PMID- 1294399 TI - HIV-1 infection in Italian blood donors during a 5 year surveillance. PMID- 1294400 TI - Human Chorionic Gonadotrophin (hCG) in the management of recurrent abortion. PMID- 1294401 TI - Human chorionic gonadotrophin (hCG) in the management of recurrent abortion; results of a multi-centre placebo-controlled study. AB - An international ten-centre double-blind trial comparing hCG with placebo in the management of habitual abortion was conducted. The dose regime for hCG used was 10,000 IU i.m. on first diagnosis of pregnancy, 5000 IU thence twice weekly to week 12, followed by once weekly up to week 16. Identical ampoulage of placebo was used. Seventy-five patients completed the trial. Thirty-six received hCG and thirty-nine placebo. 83% of the pregnancies on hCG were successful compared with 79% on placebo (P = 0.45). Of the 25 defined as having no cause for their habitual abortion history, 83% on hCG were successful, as were 85% on placebo (P = 0.73). No significant differences were found between the two therapies in terms of delivery weight, placental weight or neonatal Apgar score. This study fails to confirm previous promising placebo-controlled data advocating the use of hCG in habitual abortion. PMID- 1294402 TI - Convention for reporting amniotic fluid pressure. AB - A proposed convention sets zero pressure at atmospheric pressure at the level of the surface supporting the supine patient and takes the cm of water as the unit of measurement. This ensures that measurements made in different clinics will be comparable. Statements about 'higher' and 'lower' pressures, in different patients or in the same patient in different situations, should specify the level of the uterus to which the statement applies. PMID- 1294403 TI - Fetal malformations associated with chronic polyhydramnios in singleton pregnancies. AB - Forty-one congenital malformations were found in 28 newborns in a group of 197 cases of chronic polyhydramnios in singleton pregnancies. Of these, a total of 61% (17/28) was antenatally diagnosed ultrasonically. Nine newborns (4.5%) had malformations of the central nervous system (CNS), 9 (4.5%) cardiovascular malformations, 8 (4.1%) musculoskeletal anomalies, 7 (3.6%) malformations of the urinary and reproductive system, 4 (2%) respiratory system anomalies and 3 (1.6%) anomalies of the gastrointestinal system. Chromosomal abnormalities were found in three cases. As the association of polyhydramnios with fetal congenital anomalies is quite high (14.2% in our series), it is imperative to make a major effort to antenatally detect as many cases as possible. This means that in the case of hydramnios the following are required: ultrasound examination by an expert, echo ultrasonography when no other abnormalities are detected, and maybe even a chromosomal analysis. PMID- 1294404 TI - The influence of presentation and method of delivery on neonatal mortality and infant neurodevelopmental outcome in nondiscordant low-birthweight ( < 2500 g) twin gestations. AB - The effects of birth order, presentation and method of delivery on neonatal mortality and neurodevelopmental outcome in nondiscordant low birthweight ( < 2500 g) twin gestations were evaluated. Sixty-four sets of twins were included in the study; 29 sets were in vertex/vertex presentation (Group I), 25 sets in vertex/breech (Group II) and in 10 pregnancies the first twin was nonvertex (Group III). The rate of favorable neonatal outcome (survival and normal neurodevelopmental outcome after a 2-year follow-up) was lower in pregnancies in which at least one twin was in nonvertex presentation (50/70 vs. 52/58 P = 0.02). However, after adjustment by multiple logistic regression analysis for the effects of gestational age, birthweight, birth order and educational level of the mother, this difference was not statistically significant (odds ratio = 0.6; 95% confidence interval 0.44 to 5.9; P = 0.5). In pregnancies in which at least one of the twins was in nonvertex presentation, delivery by cesarean section did not affect the rate of favorable neonatal outcome (odds ratio = 1.8; 95% confidence interval 0.48 to 12.9; P = 0.8). The results of this study suggest that in low birthweight twin gestations, method of delivery in relation to fetal presentation has little or no effect on neonatal mortality and subsequent neonatal neurodevelopmental outcome. PMID- 1294405 TI - Prediction of light-for-gestational age at delivery in twin pregnancies: an evaluation of fetal weight deviation and growth discordance measured by ultrasound. AB - The purpose of this retrospective study was to evaluate and discuss different ultrasound methods widely used, among other things, as predictors for light-for gestational age (LGA) in twin pregnancies. The methods evaluated and compared as predictors for LGA at birth were: (1) Difference between twins in biparietal diameter; (2) difference in abdominal diameter; (3) the percentage difference in estimated fetal weight between twins; and (4) estimation of the weight deviation from the expected weight during pregnancy. The study comprised 66 twin pregnancies, examined by ultrasound scanning less than 15 days before delivery. Using Relative Operating Characteristic curves (ROC curves) estimated fetal weight deviation was the most sensitive and specific of the methods. It is stressed that fetal discordance is not the appropriate predictor of LGA at birth in twin pregnancies. PMID- 1294406 TI - Grand multiparity as an obstetric risk factor; a prospective case-control study. AB - In a socio-economically stable community with free access to medical care, a prospective comparison was made of pregnancy, delivery and neonatal data concerning 480 grand multiparas (> or = 5 deliveries) and 325 controls. The mean diastolic blood pressure was slightly higher (79.8 vs. 77.8 mmHg) among the grand multiparas and the rates of episiotomy differed greatly (5.8% in the grand multiparas vs. 45.7% in the controls). The main clinical difference was a slightly higher incidence of placental complications-i.e., praevia, abruptio and retentio (3.4% vs. 0.9%; P < 0.05) in the grand multiparas. The differences had no effect on neonatal outcome. Grand multiparity should be regarded as an obstetrical risk factor, mainly because of the higher frequency of placental complications. With good obstetric care there should be no adverse effects on the mother or the newborn. PMID- 1294407 TI - The value of anamnestic information regarding previous genital infection in male fertility investigation. AB - The study was designed to assess the value of information from male subjects under fertility investigation, regarding previous genital infection, in clarifying the causes of depressed sperm quality. Information was gathered using a questionnaire which was sent to 312 men who had previously attended our laboratory for semen analysis. A previous sexual transmitted disease (STD) in the male partner did not significantly influence the sperm quality or the pregnancy rate. However, a previous STD in the female was generally associated with a lower pregnancy rate. Previous episodes with urethral discharge, dysuria, pain with ejaculation or suprapubic discomfort had little relevance for the subsequent sperm quality. The results indicate that, in general, information provided by men under fertility investigation, regarding previous genital infections or symptoms, is only of limited value in elucidating the cause of impaired sperm quality. PMID- 1294408 TI - Plasma lipid and lipoprotein effects of transdermal administration of estradiol and estradiol/norethisterone acetate. AB - To evaluate the effect of transdermal sequential treatment with estradiol and estradiol/norethisterone acetate on lipoprotein metabolism, 25 postmenopausal women received treatment for 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day and 2 weeks a combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Blood samples for lipoprotein analyses were drawn before treatment and in estrogen and combined phases in cycles 3 and 12. Plasma total cholesterol, low (LDL) and high (HDL) density lipoprotein were all significantly reduced in both estrogen and combined phases. Eighteen of the women continued the treatment for 36 cycles. In this group the HDL-cholesterol had returned to baseline values in combined phase in cycle 24. Plasma cholesterol and LDL-cholesterol values remained significantly reduced throughout the whole study compared to the pre-trial values. The present study by transdermal sequential hormonal treatment results in a lipid and lipoprotein pattern with reduced total cholesterol and LDL cholesterol in postmenopausal women. PMID- 1294409 TI - Growth factor content in normal and benign ovarian tumours. AB - Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) content was measured in normal ovaries and benign ovarian tumours. Epidermal growth factor was present in 12.7% of normal ovaries, with a range 0.030-0.533 ng/mg DNA, and in 31.8% of benign ovarian tumours, with a range 0.1335-2.080 ng/ml DNA. TGF alpha was present in 84.5% of normal ovaries, with a range of values from 0.037-18.2 ng/mg DNA, and in 84.1% of benign ovarian tumours, with a range of 0.083-195 ng/mg DNA. The TGF alpha content in post menopausal benign ovarian tumours was significantly higher (P < 0.0001) than TGF alpha in the pre menopausal normal ovarian group. The frequency of detection and levels of TGF alpha measured were significantly higher than those of EGF in the normal ovary group (P < 0.001) and also in the benign ovarian group (P < 0.005). We conclude that TGF alpha is the predominant growth factor present in normal ovaries and benign ovarian tumours. PMID- 1294410 TI - Epidermal growth factor receptor in normal ovaries and benign ovarian tumours. AB - Epidermal growth factor receptor (EGFR) was assayed in 52 women who had normal ovaries removed at hysterectomy and in 30 women with benign ovarian tumours. The histology of each ovary was recorded. A single point screen was performed on all samples and in positive cases a full Scatchard analysis. EGFR was present in 8 of 52 normal ovaries (15.4%) and 3 contained the high-affinity component while 5 had the low affinity component. In the benign ovarian tumour group 4 of 30 tumours (13.3%) had receptor present, one was high affinity and 3 were low affinity in type. We can conclude that EGFR is detectable only at low frequency in normal and benign ovarian tumours. PMID- 1294411 TI - A prospective randomized double-blind trial of ceftriaxone versus no treatment for abdominal hysterectomy. AB - The value of preoperative prophylactic parenteral treatment with ceftriaxone at elective abdominal hysterectomy was investigated in a prospective, randomized, double-blind study, in which 157 women participated, 77 in the antibiotic group and 80 in the control group. Increased febrile morbidity and a significant preponderance of women with urinary tract infections were observed in the untreated group, whereas there was no significant difference between the two groups regarding wound infections or infiltration at the top of the vagina. We find no indication for routine prophylactic use of antibiotics at elective abdominal hysterectomy. PMID- 1294412 TI - Preoperative investigations for suspected pelvic masses. AB - Ultrasound examination was performed on 307 patients admitted to Herlev Hospital, Copenhagen, for suspicion of a pelvic tumor. Of these, 194 were operated on, 38 (19.6%) having a malignant tumor and 156 with benign conditions. A solid tumor was suspected in 72 patients on whom intravenous pyelography, barium enema, cystoscopy and rectoscopy were performed, although 11 did not undergo an intravenous pyelography and 12 did not undergo a barium enema. Intravenous pyelography, barium enema, rectoscopy and cystoscopy very seldom gave unsuspected information and never changed the indications for operation. Ultrasound examination of the kidneys, urinary tract, bowel system, liver and retroperitoneum as a complementary investigation to the gynecologic examination of the pelvic tumor gave the same information as did the barium enema, intravenous pyelography, rectoscopy and cystoscopy. Therefore, we conclude that these investigations should be carried out only in patients with symptoms from the urinary tract or the bowel system. Instead, we suggest that ultrasound examination of a pelvic mass also include an examination of the kidneys, urinary tract, bowel system, liver and retroperitoneum. PMID- 1294413 TI - Comparison of five immunoassay procedures for the ovarian carcinoma-associated antigenic determinant CA 125 in serum. AB - Interassay variability in CA 125 values was studied in 77 serum samples (covering a range of CA 125 values between 8.9 and 310 arb. U/ml as measured by the original Centocor RIA) using three 125I-labeled RIA kits (Centocor, Byk and Cis) and two enzyme-labeled immunoassays (Abbott and Roche). Taking the Centocor RIA as a reference, orthogonal regression equations resulted in slopes varying between 0.74 and 1.35, with y-axis intercepts varying between -6.5 and +6.2, and correlation coefficients ranging from 0.88 to 0.94. Compared with the results of the Centocor RIA, the EIAs of Abbott and Roche gave overall lower CA 125 values, whereas the Cis and the Byk RIAs gave higher assay results. At the 35 arb. U/ml Centocor cut-off, serum levels with the other assays varied between 23 and 53 arb. U/ml. The 65 arb. U/ml cut-off level corresponded with CA 125 serum levels between 45 and 94 arb. U/ml. When classifying CA 125 values in three clinically relevant categories based on Centocor RIA results, ('normal' < or = 35 arb. U/ml, 'slightly elevated' > 35- < or = 65 arb. U/ml and 'elevated' > 65 arb. U/ml), discordances ranged from 26% with the Cis RIA to 40% utilizing the Byk RIA. The five CA 125 assays tested do not give equal assay results. As a consequence, the interpretation of CA 125 serum concentrations should be done with caution in disease monitoring and in the assessment of ovarian masses, especially when using different serum assays. PMID- 1294414 TI - Ovarian carcinoma causing cerebellar degeneration. AB - Subacute cerebellar degeneration can be associated with malignancies. If the underlying tumor is a gynecological one, Purkinje cell cytoplasmic antibodies in serum serve as tumor markers. PMID- 1294415 TI - Postpartum periarticular hip abscess with later coxitis caused by group B streptococcus. AB - Intrapartum haematogenous spread of vaginal group B Streptococcus is rare, but it can lead to severe complications like abscesses, endocarditis and meningitis postpartum. We report a postpartum periarticular hip abscess caused by group B Streptococcus. Clinically it caused pain in the hip and a compression of the femoral nerve with motor and sensory component. Diagnosis was made by aspiration under computed tomography control. The only sign of infection was an increased sedimentation rate. After antibiotic treatment the symptoms disappeared and the abscess vanished, but it was reactivated 4 months after delivery, leading to arthritis of the hip joint. Another antibiotic treatment was administered for 8 weeks. 17 months postpartum the patient is well, but a development of a secondary coxarthrosis can not be excluded. PMID- 1294416 TI - Pulmonary complications of antepartum pyelonephritis: more alertness is needed. AB - Three cases of pulmonary complications associated with antepartum pyelonephritis are presented, in two of them tracheal intubation and mechanical ventilation were required. All three cases were related to recurrent urinary infections with failure of first line antimicrobial therapy and a concomitant usage of tocolytic therapy. The possible etiology, risk factors and clinical approach, aimed to prevent pulmonary complications in antepartum pyelonephritis are discussed. PMID- 1294417 TI - Unsuspected involvement of the female genitalia in pemphigus vulgaris. AB - A 56-year-old woman had erosions due to pemphigus vulgaris in the inner thighs and perineum. The cutaneous lesions cleared following intramuscular gold therapy. However, because of complaints of dyspareunia, a colposcopic examination was performed and involvement of the cervix was demonstrated. The need for a vaginal examination in the monitoring of pemphigus vulgaris is emphasized. PMID- 1294418 TI - Familial ovarian cancer. AB - Familial ovarian cancer occurs in approximately 5% of all ovarian cancers. Since the relation between ovarian cancer and genetic heritage has drawn much attention lately, general gynaecologists will more and more be faced with the question how to survey patients from a family with the familial ovarian cancer syndrome. We describe a patient from a family with three daughters, of which two older sisters were known to have ovarian cancer. Although our patient was closely observed, a third-stage ovarian cancer developed. With this case in mind and after a review of the literature, we will in future closely survey patients from familial ovarian cancer families from their twentieth birthday on, and recommend prophylactic bilateral oophorectomy after child-bearing age. However, we are aware of the fact that it is impossible to diagnose ovarian cancer in a premalignant phase as yet, and the benefit of a close survey might be an earlier diagnosis and not prevention. Also, prophylactic oophorectomy does not prevent the occurrence of intra-abdominal malignancies histopathologically indistinguishable from ovarian cancer. Patients should be aware of these restrictions. If, in the future, the precise chromosomal defect in ovarian cancer families is localized, prevention of ovarian cancer, but not of intra-abdominal malignancies of the same histopathology, might be within reach. PMID- 1294419 TI - Alobar holoprosencephalic embryo detected via transvaginal sonography. AB - The incorporation of high-frequency transvaginal probes in commercial ultrasonic equipment allows now for the earlier detection of fetal malformations and the possibility of interrupting pregnancy when such an anomaly is incompatible with postnatal life. We describe here a case of alobar holoprosencephaly associated with serious facial anomalies, diagnosed via transvaginal sonography during the 10th week of amenorrhea. A cytogenetic study was carried out by transabdominal chorial biopsy and diagnostic confirmation by necropsy was made after termination. In order to be able to counsel patients on the advisability of future pregnancies we stress the importance of making a cytogenetic study of the embryo. PMID- 1294420 TI - [Association of serum C3 and essential hypertension]. AB - This study was performed to assess the possible involvement of humoral immunity in essential hypertension, independently of the presence of atherosclerotic disease, which in turn may be associated with immunologic changes. Sixty-five patients without demonstrated atherosclerotic disease were selected according to clinical and arteriographic criteria, including 23 hypertensive subjects (all pharmacologically treated) and 42 controls. Mean ages (58.7 +/- 8.3(1 S.D.) years in the controls and 57.7 +/- 7.9 years in the hypertensive subjects) and sex distribution were similar in the 2 groups. Of the main risk factors, atherosclerosis, smoking, diabetes, total cholesterol and HDL-cholesterol were equivalent, while triglycerides were higher in the hypertensive subjects than in the controls (142.6 +/- 52.7 vs. 112.6 +/- 67.7 mg/dl; p = 0.0065). In these subjects' sera the immunoglobulins IgG, IgA and IgM, and the third and fourth complement components (C3 and C4) were measured. Of these variables, only C3 was higher in the hypertensive subjects than in the controls (124.3 +/- 29.3 vs. 107.8 +/- 18.4 mg/dl; p = 0.0183). Furthermore, C3 was significantly correlated with triglycerides (tau = 0.3613; p < 0.0001), but the association with hypertension was confirmed only for C3, and not for triglycerides, by multiple logistic regression (p = 0.0142). The increase in serum C3 suggests the possible implication of humoral immunity in the pathogenesis or progression of essential hypertension. PMID- 1294421 TI - [Inflammatory aneurysm of the abdominal aorta: anatomo-clinical study on 16 cases and pathogenetic hypothesis]. AB - BACKGROUND: Inflammatory aneurysms of the abdominal aorta constitute an anatomoclinical entity characterised by prominent thickening and fibrosis of the aneurysmal wall, extending to the adjoining structures. Etiology, pathogenesis and relation with atherosclerosis still remain controversial. METHODS: Sixteen consecutive patients undergoing surgery for inflammatory aneurysm of the abdominal aorta between March 1987 and December 1990 were studied (Group I); as a control, a series of 16 consecutive patients operated on in the same period for atherosclerotic aneurysm of the abdominal aorta was selected (Group II). As far as clinical history and symptoms are concerned, the comparison between the two groups revealed significant differences only for hydronephrosis (exclusively present in Group I, p < 0.05) and abdominal pain (more frequent in Group I, p < 0.01). The microscopic study of the aneurysmal wall was performed by scoring its histological features (atherosclerotic lesions, medial and adventitial fibrosis, inflammatory infiltrates and lymphatic stasis) from 1+ to 3+. RESULTS: As regards the microscopical features, atherosclerotic lesions were present in all the examined cases, whereas periadventitial fibrosis appeared in all the aneurysms of Group I and in none of Group II; the comparison between the two groups revealed further significant differences for extensive intimal calcification (exclusively present in Group II, p < 0.05), fibrous replacement of the tunica media (more thorough in Group I, p < 0.02), and the extent of inflammatory infiltrates (more prominent in Group I, p < 0.05). CONCLUSIONS: From the scarcity of pathognomonic features in both case-history and clinical presentation, the constant coexistence of prominent atherosclerotic lesions, and the progressive trend of the pathologic features, inflammatory aneurysms may be inferred to be a variant of atherosclerotic ones, characterised by a particular prominence of inflammation and fibrosis. The frequent occurrence of dilation of both periaortic lymphatic vessels and lymph node sinuses, even in "incipient" aneurysms, supports the hypothesis that it may be the lymphatic stasis which determines periaortic fibrosis. Finally, atherosclerotic components passing into periaortic fibrosis and eliciting granulomatous reaction were observed in two Group I cases featuring prominent "inflammatory" symptoms; such a finding favours the hypothesis that an immune reaction against some components of the atherosclerotic plaque may lead to the pronounced inflammatory response that is peculiar of inflammatory aneurysms. PMID- 1294422 TI - [Hemodynamic effects of enalapril in patients with non-complicated acute myocardial infarct]. AB - To evaluate the hemodynamic effects of the first oral administration of enalapril maleate, a long-acting ACE-inhibitor, in the early phase of an acute uncomplicated myocardial infarction, we studied 15 patients, in Killip class I or II, within 72 hours from the onset of symptoms. Hemodynamic measurements were obtained by a triple lumen 7 F Swan-Ganz catheter, inserted into the pulmonary artery, under control conditions and 2, 4, 6, 8 and 12 hours after 10 mg (15 patients) and 20 mg (11 patients) of the drug. Ten milligrams of enalapril reduced systolic and mean arterial blood pressure (from 118 +/- 17 to 111 +/- 18 mmHg, p < .05, and from 92 +/- 12 to 83 +/- 12 mmHg, p < .01, respectively), with a maximum effect after 4 hours from administration. Heart rate and vascular resistances showed an insignificant trend toward reduction, and no changes were observed in left ventricular systolic work index, right and left ventricular filling pressures or cardiac index. Hemodynamic changes induced by 20 mg of the drug, in a smaller group of patients, had a similar trend, which did not reach a statistical significance. In conclusion, in patients with acute uncomplicated myocardial infarction, a single oral dose of enalapril maleate is safe and well tolerated, does not induce severe hypotension, and produces potentially beneficial changes in hemodynamics. PMID- 1294423 TI - [Atrial natriuretic peptide, left ventricular mass and renin-angiotensin aldosterone system in essential arterial hypertension of a mild or moderate degree]. AB - OBJECTIVE: The relationship between plasma atrial natriuretic peptide (ANP), renin-angiotensin-aldosterone system and left ventricular mass in essential hypertension was assessed. PATIENTS AND METHODS: Immunoreactive ANP in 10 normal subjects and 20 untreated patients with mild to moderate essential hypertension was compared with echocardiographic measurement of cardiac size, function and blood pressure. Venous plasma concentrations of ANP were also studied in relation to urinary sodium and potassium excretion, as well as the renin-angiotensin aldosterone system. RESULTS: Plasma ANP was higher in hypertensive patients (25.3 +/- 13.3 pg/ml; p = 0.003) than normotensive subjects (11.1 +/- 2.7 pg/ml). In hypertensive patients, plasma ANP was inversely related to plasma renin activity (PRA) (r = -0.6; p = 0.009). No relationship was found between ANP and blood pressure, nor between the indices of left ventricular mass and function or urinary electrolytes. CONCLUSIONS: This study showed that circulating ANP is, in average, significantly increased in hypertensive patients, consistent with previous reports. Our data do not support a direct link between left ventricular mass and increased plasma ANP levels in hypertensive patients. Whether the inverse relationship between ANP and PRA in this pathologic state is a direct one or merely a secondary association has not been clearly established. PMID- 1294424 TI - [Controversies in the selection of donors in heart transplants]. AB - The shortage of ideal donor hearts has led to an increasing number of would-be heart transplant recipients who die while on the waiting list: an extension of the classical donor criteria seems necessary to expand the donor pool. In this paper, the major controversies on donor selection are presented, along with the clinical results obtained in cardiac transplantation with donor grafts not complying with standard criteria. The extension of donor age over 35 years is supported by the decreased incidence of coronary artery disease (CAD) in the Western world. In our experience, the number of donors over 40 years has increased steadily, without concomitant significant increase in postoperative short- and medium-term mortality after cardiac transplantation. The relative importance of CAD risk factors in the older heart donor is to be weighed out on a case-by-case basis. The performance of coronary angiography in 90% of the donor grafts over 50 years has led to more accurate selection. ECG minor alterations and ECHO diagnosed dyskynesias are of uncertain significance. Localized infection, transitory hypotension, brief cardiac arrest and thoracic trauma do not necessarily contraindicate heart donation. The importance of donor/recipient weight mismatch over 20% is critical only in face of high pulmonary vascular resistance. Prolonged dopamine infusion above 10 micrograms/kg/min may predict poorer function outcome. From our data, severe donor dysionemia may be very hazardous. In conclusion, our experience demonstrates that extended donor criteria do not compromise short- and medium-term clinical results of cardiac transplantation. Nevertheless, several controversial aspects of donor graft selection remain open. PMID- 1294425 TI - [Intermittent block of the left bundle branch as a cause of atypical retrosternal pain]. PMID- 1294426 TI - [Rare anatomic coronary variant. Description of a case]. AB - A case of a patient with post-infarction angina and peculiar abnormalities of the coronary arteries is reported. We describe the anatomic findings as well as the possible therapeutical options. PMID- 1294427 TI - [Fatal aortic dissection in a young woman at the 32nd week of pregnancy]. AB - Aortic dissection in young women without Marfan disease is unusual. When it occurs it is often related to pregnancy. We report a fatal case of aortic dissection in a 29-year-old woman at the end of her first pregnancy. A prompt diagnosis and surgical treatment usually permits the physician to save both mother and fetus. In this case the delay in the diagnosis was fatal for both. We retain that knowledge of this rare complication of pregnancy is useful in order to refer patients early for surgical treatment. PMID- 1294428 TI - [Prostaglandins and ischemic cardiopathy]. PMID- 1294429 TI - [The Italian Group for the Study of Streptokinase in Myocardial Infarct Sub project-3: Echocardiographic evaluation of ventricular remodelling after acute myocardial infarct. Study protocol]. PMID- 1294430 TI - [HELLP syndrome--metamorphosis of pre-eclampsia]. AB - During an eight year period, 100 patients with the diagnosis of pre-eclampsia and HELLP syndrome were treated at the Departments of Obstetrics and Gynaecology of 2 University Hospitals (Technische Universitat Munchen and Universitat Gottingen). The clinical treatment concepts, which were used in common at the two hospitals, are presented and differ from the common clinical management of pre-eclampsia. The results and therapy concepts are compared and critically reviewed. In recent years, the number of diagnoses and cases of HELLP syndrome has been increasing. Case reports, epidemiological statistics and maternal and perinatal mortality rates indicate a change of the "Gestalt" of preeclampsia due to the HELLP syndrome and its complications. PMID- 1294431 TI - [Prenatal diagnosis and therapy of adrenogenital syndrome with 21-hydroxylase deficiency]. AB - Genetic counselling of the parents is prerequisite before prenatal diagnosis and prenatal therapy of CAH. Today, chorionic villous biopsy with DNA probe is the method of choice to identify homozygous CAH-fetuses. The aim of prenatal therapy is to prevent intrauterine virilization of the external genitalia in affected female fetuses. Therefore, dexamethasone (3 x 0.5 mg/d p.o.) is given to the mother immediately when pregnancy is confirmed, before prenatal diagnosis and karyotyping is possible. After the result of prenatal diagnosis, treatment is continued until term only when the fetus is affected and female. Prenatal diagnosis and effective treatment of female CAH fetuses greatly reduces the need for corrective surgery and thus helps to alleviate anxieties of prospective parents and therefore encourages further pregnancies. However, prenatal treatment of CAH to date still is an experimental therapy [corrected]. PMID- 1294432 TI - [Umbilical blood flow relations in patients with gestosis-- gestosis-specific Doppler phenomenon]. AB - A collective of 48 pregnant women, whose pregnancies showed signs of a pregnancy induced hypertension or gestotic tendencies was examined by Doppler ultrasound. The subject of interest was the resistance along the umbilical cord. Measurements were taken both ends of the umbilical cords. Usually, a decline of the indices is seen, which makes the difference between the two ends (Delta F) turn out positive. Pregnancies with any sign of a gestotic development, showed elevated resistances at the placental end of the cord. The indices of the foetal abdominal insertion were just about the same. Delta F changed significantly in our group of patients. Here, the values of both sides either did not differ from one another or the placental indices even exceeded the foetal ones. We called this special constellation of umbilical indices a Doppler phenomenon characterising gestotic pregnancies. PMID- 1294433 TI - [Cellular immunity in pregnancy-induced hypertensive diseases]. AB - Cytokines (IL-1, sIL-2R, IL-3, IL-6, TNF-alpha, IFN-gamma, GM-CSF and neopterin) were measured in sera of 37 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy non-pregnant controls. With the exception of neopterin (p = 0.004) there were no statistically significant differences in cytokine concentrations between healthy pregnant and non-pregnant controls. No statistically relevant differences between healthy pregnant women and hypertensive patients could be found in cytokines of T-lymphocytic origin except GM-CSF in patients with HELLP syndrome (p = 0.02). Elevated levels of IL-6, TNF alpha and neopterin were observed in hypertensive women. Differences to healthy pregnant controls were statistically significant for IL-6 (p = 0.008), TNF-alpha (p = 0.009) and neopterin (p = 0.04) and were more pronounced in severe forms of the disease. These 3 parameters of monocytic origin showed significant positive correlations amongst each other. A participation of cell-mediated immunity (especially monocytes/macrophages) in the pathomechanism of hypertensive disorders of pregnancy can thus be assumed. PMID- 1294434 TI - [Monitoring daily insulin needs--an important follow-up parameter in late pregnancy in diabetic mothers?]. AB - Pregnancy is a state of natural insulin resistance, which is due to placental production of human placental lactogen (HPL), an insulin antagonising hormone, leading to a remarkable increase of insulin requirement in pregnant diabetics in the 2nd and 3rd trimester. Aim of the prospective study was the quantification of daily insulin requirement during the last 28 days before delivery in pregnant women suffering from insulin-dependent diabetes mellitus (n = 20) with and without evidence of "placental insufficiency syndrome" employing peripheral rheography as indirect parameter for placental haemoperfusion. All diabetic women included controlled carbohydrate metabolism by means of a functional insulin therapy (FIT; HbA1c in normal range < 5.8%), a multiple injection regime with frequent blood glucose self-control at least from the 2nd trimester of pregnancy. According to the results of peripheral rheography in the 34th gestational week, an impedanceplethysmographic method for quantifying peripheral haemoperfusion, patients were subdivided in a group with (B: n = 8) and without (A: n = 12) indirect evidence of placental dysfunction. Groups did not differ in maternal age, duration of diabetes, maternal weight and week of delivery (A: 39.08 +/- 1.44; B: 39.12 +/- 1.46). Mean weight of neonates was lower in group B (3319 +/- 619 g) compared to group A (3613 +/- 437 g). During a comparable state of near normoglycaemia in both groups, 7 out of 8 women in group B, but only 1 out of 12 women in group A displayed a significant decrease in daily insulin requirement from day -28 to day -3 before delivery (linear regression; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294435 TI - [Induction of labor with a new intracervically administered prostaglandin E2 gel. Report of initial experience]. AB - We report on our experience with the induction of labour using 0.5 mg of prostaglandin E2 gel (Cerviprost, Organon) intracervically. Out of 43 cases, 27 were primiparae. Indication for induction was: 10 post-term pregnancies, 9 PROM's > 24h, 12 foetal and 11 maternal indications. Mean Bishop score before induction was 3.1 and 9 hours later or at the beginning of regular contractions 6.7. In 9 of the 43 cases induction was unsuccessful. There were 23 spontaneous vaginal deliveries, 6 forceps and 5 Caesarean sections. Uterine hyperstimulation was found in 6 cases, 5 of which occurred during the first 16 inductions, and only one was seen during the following 27. A possible reason may be unrecognised extra amniotic application of the gel. Intracervical prostaglandin seems to be an appropriate method not only for cervical ripening but also for induction of labour in cases with a low Bishop score. Although side effects are rare, sufficient monitoring and control of mother and foetus are mandatory. PMID- 1294436 TI - [Occlusion of a vesicovaginal fistula with Latzko-repair]. AB - The Latzko procedure is a well-known method for the closure of small vesico vaginal fistulas occurring in the vaginal dome after hysterectomy. This method is favoured by gynaecologists. In three Departments of gynaecology, a total of 104 patients were treated. 76% had been referred from other hospitals. 56.7% resulted from gynaecological operations. In 69.2% was a benign and in 28.8% a malignant disease. In only 2 cases, the primary disease remained unknown. RESULTS: In 97 of 104 (= 93.3%) cases, the procedure according to Latzko succeeded at the first attempt. 5 of 7 recurrences were resolved by the second attempt with the same operative technique according to Latzko, signifying a secondary success rate of 98%. There were only 2 notable complications: the one, where a postoperative bladder haemorrhage attributed to anticoagulants, and the second with a bladder stone noticed 11 years after the Latzko procedure. This technique can be performed in 95% of all vesico-vaginal fistulas occurring. The fundamental advantages of its use are: short duration of the procedure, high cure rate and few complications. PMID- 1294437 TI - [Prognostic and therapeutic significance of steroid receptors in invasive breast cancer]. AB - It is generally accepted that breast cancer with positive steroid receptors has a better prognosis than with negative receptors. The aim of this study was to analyse the influence of the oestrogen (ER) and progesterone (PR) receptors regarding disease-free interval (DFI) and overall (oa) survival of 441 patients operated on in the Department of Gynaecology of the University Hospital of Zurich. Analysis of the subgroups separated according to menopausal status showed the following results: Premenopausal patients (n = 135): Only PR have a significant influence on the oa-survival (p = 0.0370), not the ER. The DFI was independent of ER and PR positive findings. Postmenopausal patients (n = 306): In this group only the ER has a significant influence (p = 0.0296) on the oa survival, not the PR. Both steroid receptors did not have any influence regarding DFI. Metastases and local recurrence occur pre- and postmenopausaly approximately at the same time, independent of the quality of the steroid receptors. The better oa-survival despite the same DFI can be explained by a better response to the therapy by patients in the premenopause with positive PR status and patients in the postmenopause with positive ER status. PMID- 1294438 TI - [Use of computer-assisted image analysis for the detection of immunohistochemical receptor status in breast cancer. Immunohistochemical densitometry receptor analysis--IRDA]. AB - A method for the evaluation of the immunohistochemical staining score of steroid receptors in breast cancer using computer-based image analysis is presented. The optical density of tumour cell nuclei was measured using kryostat sections and, using a control section as reference, an objective threshold for specific staining was defined. In intensively stained sections, a good correlation with visual scoring was achieved, but in 9 out of 16 sections, which were regarded as receptor-negative by visual scoring, a specific receptor-positive staining was demonstrated by image analysis. Next to the percentage of positive cells (PP) and the mean staining intensity (SI), a histogram of the receptor concentration in positive nuclei was calculated. The method allows, besides an objective evaluation and documentation, an exact definition of a threshold for specific receptor measurement and furthermore shows the pattern of receptor concentration in the tumour cell nuclei. Hence, the method could contribute towards a more widespread use of immunohistochemical receptor analysis. PMID- 1294439 TI - [Malaria tropica and pregnancy]. AB - The authors report on a female patient of 26 years of age suffering from malaria tropica infection in her 36th week of pregnancy with fatal outcome. The newborn (after performance of Caesarean section) was infected connatally. Although infections with malaria are rare in Europe today--especially during pregnancy- there is a probability of rising incidence on account of increasing international tourism. Therapeutic problems are expected to multiply due to the resistance of Plasmodia to antiparasitary medication. Additionally pregnancy involves the risk of a more severe course of the disease in the mother. Pregnant women should be discouraged from travelling to countries with malarial risk because of the likelihood of a high rate of abortion, danger of intrauterine retardation, increased incidence of premature deliveries and risk of connatal infection of the newborn. If such warnings cannot be heeded, the persons concerned must be given all relevant information on conventional preventive measures in accordance with WHO recommendations and drug prophylaxis as recommended by a hospital or institution dealing with tropical diseases according to updated standards. The measures to be taken must be adapted to the individual risk of exposure of the patient. PMID- 1294441 TI - [Forensic aspects of bladder and ureteral injuries in standard gynecologic operations]. AB - Damage to the efferent urinary passages during abdominal or vaginal hysterectomy cannot always be prevented no matter how carefully one may proceed preoperatively and intraoperatively. However, all possibilities of avoiding complications or at least of recognising and eliminating them before surgery, must be explored. Nevertheless, formation of vesicovaginal or ureterovaginal fistulas or of a congested ureter will be rare. In such cases, one cannot jump to the conclusion of mismanagement or a therapeutic error from the mere occurrence of damage. In each individual case, there must be an expertise and a legal judgment as to whether there has been any infringement of the legal requirement to exercise all possible medical care lege artis. Claims for damages are justified only if the conditions of an individual case show, on close examination, that such care had not been exercised. PMID- 1294440 TI - [Malignant lymphomas of the vulva and vagina]. AB - Primary appearance of a malignant lymphoma in the vulvovaginal region is extremely rare. In this paper, we report on three such cases we observed during the last few years. There was no difference in clinical manifestation compared to cancer of the vulva/vagina. The diagnosis was made using histological and immunohistochemical methods. Choice of the treatment depended upon the stage of malignancy and spreading of the tumourous changes (radiation, chemotherapy). On reviewing the literature of the last 15 years, we could not find any description of primary malignant lymphoma in the vulva and vaginal region. PMID- 1294442 TI - [Disseminated lymphangioleiomyomatosis]. PMID- 1294443 TI - [Carl Crede: in memory of the 100th anniversary of his death (14 March 1892)]. AB - Major advances taught by the German gynaecologist and obstetrician Carl Siegmund Franz Crede were the manual expression of the placenta and the prophylaxis of the gonoblennorrhoea. Under his supervision, as head of the obstetrical department of the Berlin Charite, the first exclusively gynaecological unit was founded in Europe. In 1856, he was elected head of the Department of Obstetrics of the University of Leipzig. Crede was the editor of the first 42 volumes of "Archiv fur Gynakologie". He died on March 14th, 1892, from prostatic carcinoma. PMID- 1294444 TI - [An unusual type of locomotion in mice of line 101/Hy]. AB - An unusual type of locomotion--backward movements--was revealed in the 101/HY mouse strain characterized by a chromosomal instability and the defect in DNA repair. The backward movements were found in 60% of mice belonging to the population under study. The manifestation of the character was found to vary: it was high in 16% of the animals. No age and sex differences were found. The backward movements in the 101/HY mouse strain were somewhat similar to the peculiarity in locomotion of the neurological hot-foot mouse mutants. The latter had mild anatomical alterations in the cerebellum. No obvious brain pathology was revealed in the 101/HY mice. PMID- 1294445 TI - [Structural heterochromatin and X-chromosome inactivation]. AB - Our previous studies on the expression of the G6PD and alpha-GAL genes from the X chromosome of inter-specific hybrids of voles of the Microtus genus have demonstrated an unusual pattern of X-inactivation in the parents. The observed phenomenon was explained as the presumable result of nonrandom inactivation of the X chromosomes with a heterochromatin block in crosses involving Microtus arvalis whose X lacks a heterochromatin region and also of random X inactivation when both parents had heterochromatin blocks on the Xs. Based on known models, we discuss here the possible mechanisms of the effect of heterochromatin on X inactivation; we give preference to the model postulating binding of nonhistone protein to the inactivation centre as the key event. The hypothesis we offer suggests change in chromatin conformation in the inactivation centre during packaging of heterochromatic region of a chromosome; the protein molecules diffusing along the chromosome towards the heterochromatin region by the "facilitated diffusion" mechanism may happen to be in the region of the X inactivation centre, which, being in a favorable state, binds specifically to it; as a consequence, the binding probability of protein to heterochromatin increases as compared to chromosome without heterochromatin block. PMID- 1294446 TI - [Cloning the trpBA-genes from Pseudomonas mendocina and Pseudomonas marginata]. AB - The trpBA genes of Pseudomonas mendocina and P. marginata were cloned in Escherichia coli using pBR322 as a vector. Transcription of the cloned genes took place from their own promoters, in the following order: trpB-->trpA. The latter genes were not linked to the trpF gene and could not be induced by indole glycerol phosphate. Thus, the trpBA cluster of P. mendocina and P. marginata are distinguished from that of P. putida, P. aeruginosa (trpIBA) and P. acidovorans (trpFBA). PMID- 1294447 TI - Right-to-die responses from a random sample of 200. AB - Seeking public attitudes toward the right-to-die, 200 telephone interviews were conducted with a random sample of residents in a midwestern city in the summer of 1990. Overall, 90% favored some kind of personal control over death circumstances. With semantics as an independent variable (euthanasia, mercy killing, physician-assisted suicide, or some form of personal control over death) only the group to whom "physician-assisted suicide" had been presented as a choice said "no" or "probably not" to a legalization question (p = < .0001). PMID- 1294448 TI - Alterations in perceptions of caregiving demands in advanced cancer during and after the experience. AB - Bereaved spouse caregivers (N = 65) studied during the time they were giving care were contacted a minimum of 6 months following the first interview to determine if perceptions of the demands of caregiving had changed over time. Thirty-one participated in the second phase of the study. Although managing the physical care was identified as most difficult during the time of caregiving, reflective thought about the difficulties in caregiving revealed that standing by or observing the slow deterioration of the ill spouse was perceived as most difficult. In addition, over 50% of the caregivers returning the survey at Time 2 reported personal regrets with respect to their ole as caregiver. These people wished they had sought out and utilized more resources to aid them in their caregiving activities. Recommendations for clinical work include: helping the spouses to: (a) recognize their own grief over the losses they incur, and (b) accept assistance from resources outside the home. PMID- 1294449 TI - Oregon Hospice Association: statewide data set. AB - The Oregon Hospice Association (OHA) has developed a statewide data set on persons who die while receiving hospice services. The work to date is described, including the development and refinement of data collection forms, and selected results from 1989 and 1990. Although the data set is limited, the information generated does provide OHA staff and board members, and hospice programs in the state, baseline information to use with legislators, funding sources, and the media. PMID- 1294450 TI - Developing a certificate course for hospice nurses: a Delphi survey of subject areas. AB - A Delphi survey of 16 national experts in hospice nursing was conducted to address which subject areas were the most important to include in a certification course for hospice nurses. The three-round survey elicited 70 subject areas which were ranked in order of importance according to the group opinion of the panel of experts. The means, average deviations, standard deviations, and variances for each rank were calculated. The panel showed a high degree of consensus and there was little change in ranking after the second round. The survey produced results that should be of interest to organizations concerned with developing certification courses and examination procedures for hospice nurses. PMID- 1294451 TI - Organizational factors to consider when developing a certification program for hospice nurses: a Delphi survey. AB - A Delphi survey of 16 national experts in hospice nursing was conducted to address the question of which organizational factors should be considered when developing a certification program for hospice nurses. The three-round survey elicited many factors to consider which were arranged by category and ranked in order of importance according to the group opinion of the panel. The means, average deviations, standard deviations, and variances for each factor were calculated. The panel showed a high degree of consensus and there was little change in ranking after the second round. The survey produced results that should be of interest to organizations concerned with developing a certification program for hospice nurses. PMID- 1294452 TI - Certification for hospice nurses? Assessment of need. AB - An assessment of need survey questionnaire sent to the hospice nursing community yielded a substantial return (1,550). The respondents overwhelmingly endorsed a certification process. They also emphasized the value of hospice experience and caring personal attitudes over formal educational preparation both for hospice work and for certification purposes. The preferences of these nurses for various elements of a certification process are compared to those revealed in a Delphi study of 16 hospice nursing leaders. Certain of their experimental and demographic characteristics are related to other research findings about the characteristics of hospice nurses. PMID- 1294453 TI - Production of anti-fibroblast growth factor receptor monoclonal antibodies by in vitro immunization. AB - Monoclonal antibodies against the high affinity tyrosine kinase Fibroblast Growth Factor (FGF) receptor may help define receptor epitopes involved in FGF binding and signal transduction which mediate coronary and tumor angiogenesis (the development of blood vessels). Monoclonal antibodies against the FGF receptor were made by in vitro immunization. Receptor was PAGE-purified and transblotted to nitrocellulose. The nitrocellulose was dissolved with acetonitrile, and the receptor used as antigen in an in vitro immunization system. Screening for FGF receptor positive clones was done using membrane preparations from Coronary Venular Endothelial Cells (CVEC) expressing the FGF receptor, both by Enzyme Linked Immunosorbent Assay (ELISA) and Western blot. Culture supernatants of several clones tested positive for IgM or IgG monoclonal antibodies against the FGF receptor. Antibodies were affinity purified. Ascites fluid was produced in Balb/c mice primed with Incomplete Freund's adjuvant (IFA). The monoclonal antibodies were also found to be suitable for receptor immunoprecipitation. Immunocytochemistry was done on sections from a variety of species. Further characterization of these antibodies, as well as the production of the remainder of a panel of anti-FGF receptor monoclonal antibodies, is underway. PMID- 1294454 TI - An erythroid species-specific antigen of swine detected by a monoclonal antibody. AB - A monoclonal antibody (1AC11) has been produced which recognized the glycophorin of swine red blood cells. 1AC11 was specific for swine membrane erythrocytes. No other swine cells (leukocytes, macrophages, kidney and testis cells) nor red blood cells from all the tested mammalian species (goat, human, sheep, cattle, horse, rabbit, cat and guinea pig) were recognized. There was no blood group activity detected. Immunocytochemical analysis of blood vessel in the swine pituitary tissue showed that besides membrane erythrocytes, cytoplasmic molecules were recognized in some cells. Immunoblot analysis of both membrane and aqueous phase of chloroform/methanol fractions from swine erythrocytes showed that the monoclonal antibody 1AC11 reacts with the major sialoglycoprotein of apparent molecular weight 45,000 daltons. PMID- 1294456 TI - Monoclonal antibodies to somatostatin receptor of rat brain. AB - Murine Monoclonal antibodies (MAbs) to the rat brain somatostatin (SRIF) receptor were produced. Sp 2/0 myeloma cells were fused with splenocytes of Balb/c mice immunized with the soluble rat brain SRIF receptor which was partially purified by gel-filtration chromatography. Screening by radioligand ([125I-Tyr11]SRIF-14) binding inhibition assay yielded three stable cell lines producing IgG1, IgM, or IgA antibody. Autoradiographic study of the polyacrylamide gel electrophoresed under nondenaturing conditions revealed that these MAbs inhibited the ligand binding to the receptor, regardless of their incubation with the receptor prior to the ligand binding. The results suggest that the MAbs produced are the antibodies to the ligand binding site of the receptor, and bind to the receptor in competition with the ligand. PMID- 1294455 TI - Preparation and binding specificity of a monoclonal antibody recognizing 3-deoxy D-manno-2-octulosonic acid (Kdo) in lipopolysaccharides of Re chemotype. AB - A mouse monoclonal antibody (MAb E1) was raised against the lipopolysaccharide (LPS) of the Re mutant R595 of Salmonella minnesota. This IgG3 antibody (MAb E1), unstable at low pH and low ionic strength, was purified by chromatography on QAE Sepharose A50. The binding specificity of MAb E1 was characterized by direct and inhibition enzyme immunoassays, using natural LPSs from different strains and chemotypes, and synthetic analogs of LPS substructure of the 3-deoxy-D-manno-2 octulosonic acid (Kdo) and Lipid A regions. Among various LPSs, MAb E1 reacted exclusively with those of Re-chemotype. It recognized alpha-Kdo- monosaccharide and disaccharide structures present as non-reducing side chains in various Re type LPSs and synthetic antigens. The antibody did not react with Lipid A or various lipids, and the presence of the lipid region was not necessary for the reaction. The recognition of the epitope was not reduced by the presence of a substituent at O-8 of one of the two Kdo units present in the Re LPS from Proteus mirabilis, but the reaction was inhibited by phosphorylation of O-4 of Kdo, by the proximity of core (heptose) or Lipid A (acylated glucosamine) residues, or by certain LPS-LPS interactions. PMID- 1294457 TI - Production and characterization of two monoclonal antibodies to human glutathione peroxidase. AB - Glutathione peroxidase (GSH-Px) is an important selenium-containing enzyme which protects cells from oxidative damage. Two hybridoma clones (GPX-121 and GPX-347), producing mouse IgG1 monoclonal antibodies specific for GSH-Px, were established. Immunoblot analysis revealed that GPX-347 was specific for human GSH-Px, while GPX-121 cross-reacted with human, rat, mouse and rabbit GSH-Px. Correlation between GSH-Px content and its enzymatic activity was investigated in erythrocytes of 76 humans and in human lung adenocarcinoma PC-9 cells by using a sandwich type ELISA. The results indicated that GSH-Px activity was expressed higher than expected from GSH-Px content especially in the range of low GSH-Px concentration. PC-9 cells selenium depleted medium did not stain but the cytoplasm of PC-9 cells grown in medium supplemented with selenium stained strongly. PMID- 1294458 TI - Generation of murine triomas secreting bi-specific monoclonal antibodies that recognize HBsAG ad and ay subtypes. AB - We report the generation of murine triomas by fusing splenocytes from mice previously immunized with HBsAg ay-subtype and a hybridoma, secreting anti-HBsAg ad-subtype monoclonal antibody, which was rendered HGPRT- by induced mutagenesis with N-methyl-N'nitro-N-nitrosoguanidine. The fusion yielded a 83.8% of hybrids showing the antigen specificity of the parental hybridoma and a 16.1% of bi specific monoclonal antibodies. One of them, coded as 1C8A5, showing a heavy chain isotype (IgG1/IgG2b) was used as capture reagent in an ultramicro-ELISA. As little as 0.78 I.U. of both HBsAg ad- and ay-subtypes could be realiably detected. PMID- 1294459 TI - A MAb-based ELISA for detecting circulating antigen in CSF of patients with neurocysticercosis. AB - A monoclonal antibody (MAb)-based enzyme-linked immunosorbent assay (ELISA) was evaluated for detecting circulating antigen (CAg) in the cerebrospinal fluid (CSF) of patients with neurocysticercosis. CAg of Cysticercus Cellulosae was detected in 95 out of 116 patients with neurocysticercosis. Of the 21 neurocysticercosis patients in whom CAg was not detected, 14 had only higher density spots, 3 had one or two lower density spots and 4 had no obvious damage in their brain Computed Tomography (CT) scans. CAg was also not detected in CSF samples of patients with other diseases of the central nervous system. These included cerebral tumor, encephalopyosis, brain trauma, viral meningitis and cerebral hemorrhage. Detecting CAg with MAb-based ELISA is better than any previously available methods for the diagnosis of active neurocysticercosis. PMID- 1294460 TI - Conformational transitions and specific heat anomaly in poly(dG-dC) and its methylated analogue. AB - The Zimm and Bragg theory of the helix<-->coil transition has been modified to explain order<-->order transitions in polynucleotides, in particular B<-->Z<- >psi(-)<-->coil transitions in poly(dG-dC) and poly(dG-me5dC). Lambda anomalies in specific heat measurements around the transition point have also been explained by a further modification of the same theory. Theoretical results are found to be in good agreement with the experimental data. The nucleation parameter is consistent with the stabilization/destabilization of the ordered states (Z helix) under various environmental conditions, e.g. methylation of cytosine residue at C5 position or change in the cationic concentration of the solvent. PMID- 1294461 TI - Solution conformation of a model hexapeptide containing RGD sequence. AB - The solution conformation of a model hexapeptide Asp-Arg-Gly-Asp-Ser-Gly (DRGDSG) containing the RGD sequence has been studied in DMSO-d6 as well as in aqueous solution (H2O:D2O/90:10%) by 1H NMR spectroscopy. The unambiguous identification of spin systems of various amino acid residues and sequence specific assignment of all proton resonances was achieved by a combination of two dimensional COSY and NOESY experiments. The temperature coefficient data of the amide proton chemical shifts in conjunction with the vicinal coupling constants, i.e. 3JNH-C alpha H, NOESY and ROESY results indicate that the peptide in both the solvents exists in a blend of conformers with beta-sheet like extended backbone structure and folded conformations. The folded conformers do not appear to be stabilised by intramolecular hydrogen bonding. Our results are consistent with the flexibility of RGD segment observed in the NMR studies on the protein echistatin containing the RGD motif (references 23-25). PMID- 1294462 TI - Positron annihilation studies in lysozyme and catalase. AB - Positron annihilation studies have been carried out in two enzymes, lysozyme and catalase. Temperature dependence of the positron lifetimes in these two enzymes has been investigated. The results explained in terms of the free volume model and fluctuations between different conformational microstates of enzyme structures provide a new insight into the mechanism of bio-activity of these enzymes. PMID- 1294463 TI - Effect of coenzymes on the quaternary structure conformation of glyceraldehyde-3 phosphate dehydrogenases of mung beans and rabbit muscle. AB - Kinetics of thermal inactivation of glyceraldehyde-3-phosphate dehydrogenases of mung beans and rabbit muscle have been studied under different pH conditions in the absence and presence of various concentrations of NAD+ and NADH. The data have been discussed with respect to the effect of the coenzymes on the quaternary structure symmetry of the two enzymes and their binding isotherms. Both the (homo tetrameric) apo-enzymes exhibit biphasic kinetics of thermal inactivation, characteristic of C2 symmetry, at lower pH values and a single exponential decay of enzyme activity, characteristic of D2 symmetry, at higher pHs. In each case, NAD+ has no effect on the biphasic kinetic pattern of thermal inactivation at lower pH values, but NADH brings about a change to single exponential decay. At higher pH values, NADH does not affect the kinetic pattern (single exponential decay) of any enzyme, but NAD+ alters it to biphasic kinetics in each case. The data suggest that NAD+ and NADH have higher affinity for the C2 and D2 symmetry conformation, respectively. With mung beans enzyme, the effect of NAD+ on the two rate constants of biphasic inactivation at pH 7.3 is consistent with a Kdiss equal to 110 microM. The NAD(+)-dependent changes in the kinetic pattern of thermal inactivation of this enzyme at pH 8.6 suggest a positive cooperativity in the coenzyme binding (nH = 3.0). In the binding of NADH to the mung beans enzyme, a weak positive cooperativity is observed at pH 7.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294464 TI - Role of serine esterase in hydrogen peroxide-mediated activation of phospholipase A2 in rabbit pulmonary arterial smooth muscle cells. AB - Exposure of rabbit pulmonary arterial smooth muscle cells to hydrogen peroxide cause dose-dependent stimulation of [14C] arachidonic acid (AA) release and enhancement of the cell membrane-associated phospholipase A2 activity as well as of the cell membrane-bound serine esterase activity tested against synthetic substrate p-tosyl-L-arginine methyl ester. While pretreatment of cells with serine protease inhibitors, viz. phenyl methyl sulphonyl fluoride, diisopropyl fluorophosphate and alpha-1-proteinase inhibitor, and antioxidant vitamin E prevents H2O2 stimulation of AA release and the cell membrane-bound serine esterase and PLA2 activities, that with actinomycin D and cycloheximide is devoid of any effect on H2O2 caused stimulation of AA release and the smooth muscle cell membrane associated serine esterase and PLA2 activities. Treatment of the smooth muscle cell membrane suspension with the serine protease trypsin markedly stimulates PLA2 activity. These results suggest that on exposure to H2O2 the smooth muscle cell membrane-bound serine esterase plays an important role in stimulating the cell membrane associated PLA2 activity thereby resulting in an increase in AA release. PMID- 1294465 TI - Inactivation and reactivation of horseradish peroxidase immobilized by various procedures. AB - Horseradish peroxidase (HRP) immobilized by coupling the amino acid side chain amino groups or carbohydrate spikes to the matrix has been studied for its resistance to heat, urea-induced inactivation and ability to regain activity after denaturation in order to understand the influence of the nature of immobilization procedure on these processes. The various immobilized preparations were obtained and their properties studied: Sp-HRP was obtained by direct coupling of HRP to cyanogen bromide-activated Sepharose, Sp-NHHRP by coupling periodate oxidized and diamine-treated enzyme to the cyanogen bromide activated Sepharose, SpNH-COHRP by coupling periodate-treated enzyme to amino-Sepharose and SpCon A-HRP by binding of the enzyme on Con A-Sepharose. All the immobilized preparations exhibited higher stability against heat-induced inactivation as compared to the native HRP. Sp-NHHRP was most stable followed by Sp-HRP, SpNH COHRP and SpCon A-HRP. Sp-NHHRP was also superior in its ability to regain enzyme activity after thermal denaturation, although Sp-HRP regained maximum activity after urea denaturation. Inclusion of Ca2+ was essential for the reactivation of all preparations subsequent to denaturation by urea. PMID- 1294466 TI - Spectral evidence for the oxidation of beta-hydroxybutyrate to acetoacetate: diminution of spectra by glucose and chloride. AB - Chemical oxidation of beta-hydroxybutyrate (beta-OHB) to acetoacetate (AcAc) has been carried out by a simple and new method employing potassium persulphate as an oxidising agent. Under the conditions of assay, beta-OHB (0.079-0.395 microM) was instantaneously oxidised to AcAc and the authenticity of the oxidised product was proved by absorption spectroscopy. A common absorption maxima at about 446 nm was observed in all the spectra recorded for the product (AcAc-complex) obtained after the oxidation of beta-OHB (0.079-0.395 microM) to AcAc followed by coupling with diazotized p-nitroaniline. This absorption maxima was almost equal to that obtained for AcAc-complex using AcAc as reference standard. It implies that AcAc formed by the chemical oxidation of beta-OHB is identically similar to the AcAc used as reference standard for the study. This fact was further strengthened when absorption spectra, recorded either individually or in combination (mixed-type), exhibited a single peak with a common absorption maxima at about 446 nm. Absorption spectra was found to be partially diminished by glucose (1.77 microM) and chloride (17.1 microM), while almost complete diminution of absorption spectra was observed at higher concentration of glucose (8.88 microM) and chloride (51.3 microM). PMID- 1294467 TI - Characterization of aliphatic amine 1,4-diazobicyclo (2,2,2) octane-induced stimulation of beet spinach thylakoid electron transport. AB - Electron transport activity of beet spinach thylakoids was enhanced in the presence of aliphatic amine, DABCO (1,4-diazobicyclo (2,2,2) octane), a hydrophilic proton trapping agent. The extent of stimulation was pH-dependent and similar to the effect of the uncoupler ammonium chloride on electron transport. The stimulation of whole-chain (H2O-->MV) electron transport activity was observed only at high (rate-saturating) light intensity. The light-induced proton uptake coupled to electron transport of thylakoid was also arrested by DABCO, suggesting that DABCO uncouples thylakoid phosphorylation by proton trapping. PMID- 1294468 TI - Identification and characterization of mutations in 'X' region of a hepatitis B virus carrier. AB - A defective form of Hepatitis B virus (HBV) was identified in an apparently healthy voluntary blood donor, who was positive for the presence of HBV by dot blot hybridization, but did not have any serological markers of HBV infection. Two regions, part of X and part of surface antigen genes, were amplified by polymerase chain reaction, cloned and sequenced by Sanger's dideoxy chain termination method. The base sequence analysis revealed that the HBV mutant belonged to ayw serotype and showed three point mutations, in the form of deletions at nucleotides number 1402, 1438 and 1450. Such mutations in the 'X' region, and their likely presence elsewhere, could explain altered antigenic expression. PMID- 1294469 TI - Physicochemical characterization and phylogenetic comparison of fish lens proteins. AB - The composition of soluble eye lens proteins from four chondropterygiian and fourteen teleostean fishes were analyzed for heterogeneity in MW and pI. Lens proteins from all the fish species studies are distributed in the pI range 4.3 9.0 with polypeptides in the range 17,500-31,000 Da. Phylogenetic trees are constructed based on the observations. PMID- 1294470 TI - Purification of C-reactive protein from Channa punctatus (Bloch). AB - C-reactive protein (CRP) is found to be a normal component of serum of freshwater air-breathing murrel Channa punctatus. Based on the property of binding with C polysaccharide (CPS) of pneumococcus bacteria in presence of Ca2+, CRP was purified by phosphorylcholine-Sepharose affinity column chromatography. Molecular weight of the intact protein molecule was estimated to be approximately 141,000 by gel filtration. In non-reduced and reduced conditions the molecule showed molecular weight approximately 28,000 and 14,000 respectively in SDS-PAGE. Monospecific antisera was raised against the affinity purified CRP and used as a tool to detect CRP in the hepatic cytosol and egg extract. The level of CRP in the normal serum was estimated to be 220 micrograms/ml. PMID- 1294471 TI - Reconstitution of denatured E. coli alkaline phosphatase with E. coli ribosome. AB - E. coli alkaline phosphatase was denatured by physical/chemical means. In vitro reconstitution of this denatured enzyme was assisted by 70S E. coli ribosome, as shown by the recovery of its catalytic competence. Almost total recovery of activity of the totally inactivated enzyme was obtained in presence of equimolar concentration of 70S ribosome at 50 degrees C. PMID- 1294472 TI - Purification of erythrocyte cytochrome P-450 from goat and chick. AB - Cytochrome P-450 has been purified from goat and chick erythrocytes and characterized. Goat erythrocyte cytochrome P-450 content was higher than that of chick erythrocytes cytochrome P-450. Elution profile of purified protein from DEAE-cellulose column showed a single peak. The catalytic activities of aminopyrine-N-demethylase and acetanilide hydroxylase were found to be higher in purified proteins. Molecular weight was determined by SDS-polyacrylamide gel electrophoresis. PMID- 1294473 TI - Effect of vanadate on tryptophan metabolism in streptozotocin diabetic rats. AB - Administration of sodium orthovanadate (0.3 mg/ml) through drinking water for 20 days to streptozotocin-induced diabetic rats resulted in reversal of markedly elevated activities of some of the key enzymes of tryptophan-niacin pathway, viz. hepatic and renal aminocarboxymuconate semialdehyde decarboxylase and hepatic tryptophan oxygenase, to normal levels without restoring the elevated blood sugar level to normal state. However vanadate administration to normal rats did not cause any significant change. PMID- 1294474 TI - Effect of amiodarone, an antiarrhythmic drug, on serum and liver lipids and serum marker enzymes in rats. AB - Administration of amiodarone (AD) to rats leads to marked damage to liver, as evidenced by pathological changes and significant increases in activities of serum marker enzymes and levels of lipids like cholesterol and phospholipids with no alteration in the triglyceride levels. The risk factor, that is the total cholesterol/HDL cholesterol ratio, exhibited increase in the experimental animals, indicating that amiodarone treatment may lead to the development of coronary heart disease. PMID- 1294475 TI - CDRI-85/287: studies on competition to estrogen binding sites in the immature rat uterus. AB - Ability of compound CDRI-85/287, a new nonsteroidal antiestrogen with negligible inherent estrogenicity, to inhibit uptake of 3H-estradiol (3H-E2) by the immature rat uterus in vivo was investigated. Different doses of 85/287 were administered either intraperitoneally 30 min before 3H-E2 or orally 1 and 6 hr before 3H-E2. A dose dependent inhibition in 3H-E2 uptake was observed after administration of the compound by either route and was 69% at 50 micrograms/rat ip dose and 80% at 2.5 mg/kg po dose. In in vitro competitive binding assay, however, the compound showed poor affinity (RBA 0.42% of estradiol-17 beta) for cytosolic estrogen receptors. Considering the potent anti-estrogenic as well as anti-implantation efficacy of the compound, its action in vivo appears to be mediated via its active metabolite(s). PMID- 1294476 TI - Effect of depot medroxyprogesterone acetate and testosterone ananthate on the testis of albino rats: ultrastructural and biochemical studies. AB - Male albino rats were treated with depot medroxyprogesterone acetate (1 mg/animal/day) + testosterone ananthate (100 micrograms/100 g body weight/day) for 30 and 60 days. After 30 days of treatment, all the testicular enzymes like beta-glucuronidase, hyaluronidase, sorbitol dehydrogenase, lactate dehydrogenase, acid and alkaline phosphatase, registered non-significant decrease in their values. Fifty percent of the treated animals achieved sterility after 30 days of treatment. After 60 days of treatment the testis showed degenerative changes in Golgi phase and late spermatids. Changes in the Golgi phase spermatids were related with degeneration of the nuclear membrane. Changes in the late phase spermatids included mitochondrial hypertrophy of the midpieces, membrane lysis, absence of cristae and degeneration of annulus leading to detachment of tail. Cytoplasm of luminal area displayed hypertrophied mitochondria devoid of cristae, prominent appearance of Golgi bodies, intense lysosomal activity and ample vacuolation. Tail fragments of degenerated spermatids prevailed in luminal cytoplasm. Except for beta-glucuronidase which registered a significant decrease, levels of all the other testicular enzymes, viz. hyaluronidase, lactate dehydrogenase, sorbitol dehydrogenase, acid phosphatase and alkaline phosphatase were within their control limits. The ultrastructural and biochemical changes are correlated. PMID- 1294477 TI - Ultrastructural specialization of intestinal epithelium over Peyer's patches in the bonnet monkey, Macaca radiata. AB - The follicle associated epithelium (FAE) which separates the lymphoid follicle of Peyer's patch from the gut lumen is known to have specialized cells called M cells or "microfold" cells in man and certain animals. These cells are considered to be involved in antigen uptake and transport. Our light microscopic study of the small intestine of bonnet monkeys suggested the presence of such specialised cells in FAE. We have confirmed the presence of M cells in bonnet monkey FAE having ultrastructural features very similar to those of human M cells. PMID- 1294478 TI - Evaluation of the modulatory influence of food additive-garam masala on hepatic detoxication system. AB - Potential chemopreventive role of an Indian food additive-garam masala has been assessed through its impact on the hepatic levels of detoxication enzymes like glutathione S-transferase (GST), cytochrome b5 (cyt. b5) and cytochrome P-450 (cyt. P-450), and acid soluble sulfhydryl (-SH) content in 8-9 weeks old Swiss albino mice of either sex fed on the 0.5%, 1.0% and 1.5% (w/w) garam masala in the diet for 10 days. The data from this short term study revealed the significant but dose-independent alteration in the levels of detoxication system enzymes. The results suggest the possible chemopreventive potency of this widely used food additive by being a bifunctional inducer of detoxication system. PMID- 1294479 TI - Toxicities, LD50 prediction and in vivo neutralisation of some elapid and viperid venoms. AB - Toxicity levels of elapid (Naja naja and Naja oxiana) viperid (Vipera lebetina and Vipera russelli) venoms for mice and rat for intraperitoneal intravenous and intramuscular routes have been determined. The data have been analysed using a mathematical expression to calculate lethal venom concentrations in human snake bite cases. Further, in vivo neutralisation of snake venom potency (after experimental injection) using high voltage-low current electric shock treatment has been attempted. This treatment postponed the death further by 60-90 min in mice in case of elapid envenomation. In case of viperid envenomation such a postponement of death time was not noticed. The death postponement induced by the shock treatment probably refers to structural impairments that occur at molecular level in venom components and their consequent altered interactions with the target tissue or system. PMID- 1294480 TI - Curative effect of methionine on certain enzymes of chick kidney cortex under lanthanum toxicity situation. AB - Acute single dose administration of lanthanum chloride (250 mg/kg body wt, ip) to chicks have been found to alter the levels of enzymes of the antioxidant defence system of chick renal cortex fractions. Such changes involved significant decrease in activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase and catalase of kidney epithelial cells. However glutathione-S-transferase activity was not altered. Glutathione and total thiol contents were decreased while lipoperoxidative reactions in kidney-cortex was significantly enhanced. The data indicate that amelioration of lanthanum toxicity condition by methionine supplementation may be due to the methionine serving as a precursor of glutathione. PMID- 1294481 TI - Effects of Azadirachta indica A Juss on some biochemical, immunological and visceral parameters in normal and stressed rats. AB - Effects of A. indica (AI) were evaluated on some biochemical, immunological and visceral parameters in normal and stress rats. AI (100 mg/kg) lowered blood glucose, triglyceride and SGOT levels in normal rats, and attenuated stress induced elevations of cholesterol and urea levels. In rats immunized with SRBC, AI enhanced the humoral antibody response to the antigen. Further, AI facilitated the footpad thickness response to SRBC in sensitized mice and also enhanced leucocyte migration in immunized rats. In stressed rats, AI significantly attenuated the stress-induced (a) suppression of humoral immune response and (b) gastric ulcerogenesis. These results are discussed in light of the possible mechanisms involved in the effects of AI in normal and stressful situations. PMID- 1294482 TI - Biopharmaceutical studies of spirobishexahydropyrimidine. AB - Oral administration of spirobishexahydropyrimidine showed an increase in the activity of serum transaminases, lactate dehydrogenase and alkaline phosphatase. Biological half life and other pharmacokinetic parameters showed rapid absorption and slow elimination of the drug. PMID- 1294483 TI - Metal uptake by mycelia during submerged growth and by sporocarps of an edible fungus Volvariella volvacea. AB - Uptake of a few metals by V. volvacea was determined during submerged growth of the organism in sublethal concentration of each metal salt. The uptake of Pb2+ and Hg2+ was 5 and 5.23 micrograms g-1 respectively while that of Cu2+ was 500 micrograms g-1 under experimental conditions. Treatment of spawned substrate separately with different metal salts showed maximum and minimum uptake of Pb2+ (100 micrograms g-1) and Cd2+ (2.93 micrograms g-1) respectively by sporocarps. All metal salts at test concentrations reduced biological efficiency of sporocarp production but markedly by Co2+. Cd2+ and Co2+ were highly toxic to mycelia and sporocarps respectively. The uptake of Cu2+ by mycelia and Pb2+ by sporocarps were highest among the five metals tested. Metal toxicity, tolerance and uptake capacity of V. volvacea differ considerably with concentration of metal ions. PMID- 1294485 TI - Phaseolus vulgaris L. var. HUR 15--a potential indigenous source for commercial PHA preparation. AB - Mitogenic potential of the partially purified lectin from P. vulgaris isolated by ammonium sulphate precipitation was assessed by lymphocyte transformation test (LTT) and was compared with three commercially available phytohemagglutinins (PHA). The blast inducing capacity and mitotic index analysis revealed that this preparation has potential to be used in the indigenous commercial production of PHA which is routinely used for human chromosomal studies from the peripheral blood culture at, at present, is imported. PMID- 1294484 TI - Role of free radicals in Plasmodium berghei infected Mastomys natalensis brain. AB - Lipid peroxide, lipid hydroperoxide, reduced glutathione, oxidised glutathione, lipofuscin contents and the activity of the enzyme superoxide dismutase were assessed in P. berghei infected M. natalensis brain. The results showed significant increase in the levels of lipid peroxides, lipid hydroperoxides and lipofuscin in brain subcellular fractions of P. berghei infected M. natalensis. Furthermore, a depressed superoxide dismutase activity was observed along with regulation in glutathione content. An elevated level of lipid peroxidation products along with depressed activity of scavengers in brain during malaria highlights the role of free radicals in malarial pathology. PMID- 1294486 TI - Rationale for chemotherapy of tuberculosis and current recommendations. PMID- 1294487 TI - Drug therapy in malnutrition. PMID- 1294488 TI - Reasons for partial/non-immunization with oral polio vaccine/triple antigen among children under five years. AB - To identify the reasons for non-immunization/postponing immunization, parents of 615 poliomyelitis (APM) children and 908 children attending the Outpatient Department (OPD) for other ailments were interviewed. A total of 165 (26.9%), 185 (30.1%) and 264 (43%) among APM and 645 (71%), 183 (20.2%) and 80 (8.8%) among OPD children were immunized, partially immunized and unimmunized, respectively. Forty two per cent and 21% among parents of APM and OPD children, respectively in the unimmunized group were unaware of the need for immunization. The other reasons are minor illnesses, lack of interest, fear of side reaction, non availability of vaccine or vaccinator. The decision to withhold immunization was mostly by parents when the child had some minor illnesses, mostly respiratory infections. It is recommended to educate the health personnel-clinicians and para clinical workers by seminar and training and the public through mass media and group contact on the need for and completion of the immunizations. PMID- 1294489 TI - Prophylactic theophylline infusion for prevention of apnea of prematurity. AB - To assess if there was any advantage in the prophylactic use of theophylline to prevent apnea in preterms, we treated 56 preterms (Group A) < 34 weeks gestation with theophylline infusion and compared these with 25 age and weight matched preterms (Group B) who received no therapy. Aminophylline (25 mg/ml) was infused from admission in all neonates (group A) at rates ranging 0.2 to 0.38 mg/kg/h and blood levels estimated on an Abbots TDX analyser by Fluorescence Polarization Immunoassay, after 5 days infusion. All neonates (Groups A + B) were monitored on a Corometric 505 neonatal monitor. In Group A, 1/48 developed primary apnea while in Group B, 4-21 had primary apnea (p < 0.05). Serum theophylline ranged from 2.3 to 39.5 micrograms/ml with a mean of 12.7 micrograms/ml. The mean serum level of theophylline in 4 cases who exhibited clinical evidences of toxicity was 30.1 micrograms/ml. A statistically significant difference (p < 0.05) was noted in birth weight and serum level inspite of similar infusion rates of theophylline. A linear correlation r = 0.65 was noted between serum level and infusion rate. Multivariate regression analysis, between birth weight and gestational age to serum level, showed a linear correlationship only between birth weight and serum level (r = 0.45). PMID- 1294490 TI - Prevention of hypoglycemia: a controlled evaluation of sugar fortified milk feeding in small-for-gestational age infants. AB - The study population included 110 term healthy small-for-gestational age (SGA) infants having a blood sugar of > 30 mg/dl at the age of < 30 minutes. They were randomized into two groups; (a) Group I (study group) received sugar-fortified milk formula and (b) Group II (control group) received standard milk formula. A minimum of 80 ml/kg/24 hour of milk was given. The first feeding was given within 45 minutes of birth and subsequently at 2 hours of age and then every 2 hourly till the age of 24 hours. The blood sugar (initial within 30 minutes of birth) was monitored at the age of 2, 4, 12 and 24 hours by dextrostix. The babies on fortified feeds received significantly (p < 0.001) higher amount of carbohydrate (8.1 mg/kg/min) as compared to those on standard milk (5.1 mg/kg/min). The incidence of hypoglycemia was reduced significantly (p < 0.01) by the sugar fortified feeds. The mean blood sugar level in babies receiving fortified feeds was significantly higher at all the ages as compared to those receiving standard feeds. Nearly all the babies who subsequently developed hypoglycemia had a preceding blood sugar value of less than 60 mg/dl. The study highlights that sugar-fortified milk feeds are useful in preventing hypoglycemia in SGA infants and should be routinely recommended along with breast feeding in developing countries especially when facilities for monitoring of blood sugar are unsatisfactory or not available. PMID- 1294491 TI - Sleep pattern and night awakening in healthy infants. AB - Sleep pattern and night-awakening were studied in 500 healthy infants by a semistructured interview method. A total of 92.2% infants shared bed with their mothers, 6.8% with grand parents and 1% with fathers. Paternal participation at bedtime was observed to be insignificant. Infants of non-working mothers and families with vegetarian habits slept significantly more as compared to the working mothers and families with non-vegetarian habits. Night-time awakening was reported in 96% of the infants. If a child is functioning well in other areas of life, parents can be assured that the problem is not of serious concern and unnecessary medication of infants should be avoided. PMID- 1294492 TI - Infant mortality in Pondicherry--an analysis of a cohort of 8185 births. AB - Infant mortality rate is one of the 12 global indicators for monitoring Health for All. Reliable data on infant mortality are not available for the majority of developing countries including India. To plan strategies for bringing down the rate and, later, to evaluate them, 'Cause Specific Rates' would be necessary. Pondicherry has achieved low rates of infant mortality. A study was conducted in the Anganwadis of Pondicherry to determine the causes of infant deaths. The 8185 children born between 1-4-1987 and 31-3-1988 in Pondicherry formed the study group. The Anganwadi workers collected information on the cause of death for the 222 children dying within the first year. The infant mortality rate was 27.1 per 1000 live births. Acute respiratory infections and diarrheal diseases accounted for 45% of the deaths. PMID- 1294493 TI - Renal parameters during infancy. AB - In a prospective study we estimated common renal parameters in 48 full term normal neonates, of which 15 were also tested at 6 months and 12 months of age. The mean levels of serum creatinine, were high at birth (0.73 mg/dl) but normal for age at 6 and 12 months; uric acid followed a similar trend. The blood pH and bicarbonate were low at birth (7.28 and 20.36 mEq/L, respectively) reached normal adult values by 12 months; chloride levels were high at birth (110 +/- 5 mEq/L) and normal at 6 months. The plasma renin activity was higher than normal all throughout the first year (27.1, 416.8, 64.8 ng/ml/hr by RIA). Plasma aldosterone values were high at birth (1387.5 pg/ml) and reached normal level (301.6) at 12 months. Renal length and volume as assessed by ultrasonography compared well with American standards. Urinary constituents were variable due to breast feeding up to 6 months and varied diet during the weaning period. This study shows that mild metabolic acidosis and hyperchloremia due to immaturity of renal acidification mechanism and high renin and aldosterone levels due to partial nonresponsiveness of distal tubules are normal variables in babies from birth to 6 months. The levels of serum creatinine and uric acid are high at birth and in assessing renal functions this should be borne in mind. PMID- 1294494 TI - Commercial oral rehydration solutions--pitfalls, knowledge, attitude and practices. AB - Locally available commercial preparations of oral rehydration solutions (ORS) were analyzed for their composition, package instructions and availability. A survey from 50 chemist stores, revealed that ORS packets available belonged to 28 different pharmaceutical companies. None of the shops stored more than five different brands and alternate preparations were handed over the counter freely. Only 48% of the available ORS formulations had the WHO recommended composition. In about one-fourth preparations, the sodium concentration was 30 mEq or less per litre. Forty-one per cent solutions had glucose concentrations more than 2%. The glucose and sodium ration of 1:1 was maintained in only 48% of the formulae. Bicarbonate and citrate both were used with almost equal frequency in these preparations. Cost, flavor, additional ingredients and package instructions varied widely in different packets. ORS formulations most commonly found in the drug stores had low sodium and high glucose concentration. The attitude of doctors and nurses of Pediatric Department and Chemists towards commercial ORS was also studied. While 92% doctors were aware about WHO-ORS, none of the chemists and only 4% nurses had this awareness. All the respondents could remember only up to 3 or 4 brand names and except 30% doctors, none were aware about the composition of those brands of ORS. Regarding importance of composition, preparations and precautions, practically nobody was up to the mark, but doctors were definitely better as compared to nurses and chemists. PMID- 1294495 TI - Renal osteodystrophy with multiple osteolytic lesions in the skull. PMID- 1294496 TI - Pulmonary aplasia: a CT appearance. PMID- 1294497 TI - Acquired immunodeficiency syndrome (AIDS) with lymphocytic interstitial pneumonitis (LIP) in a multi transfused child with thalassemia major. PMID- 1294498 TI - Nesidioblastosis: ultrastructural and immunohistochemical observations. PMID- 1294500 TI - Angelman's "happy puppet" syndrome. PMID- 1294499 TI - Paraplegia following cisternal puncture in thoracic osteochondroma. PMID- 1294501 TI - Maternal knowledge of childhood immunization. PMID- 1294502 TI - Osteoma of the tongue: a rare cause of upper airway obstruction. PMID- 1294503 TI - Acute acalculous cholecystitis in typhoid fever. PMID- 1294504 TI - Conservative treatment of bile ascites in a neonate. PMID- 1294505 TI - Intraperitoneal CSF pseudocysts following ventriculo-peritoneal shunts. PMID- 1294506 TI - Single dose antibiotic therapy for urinary tract infection. PMID- 1294507 TI - Progeria. PMID- 1294508 TI - Multiple giant mesenteric cysts. PMID- 1294509 TI - Tuberculosis in a BCG vaccinated child with leprosy. PMID- 1294511 TI - UTIs in the 90s. Pathogenesis and management. PMID- 1294510 TI - Hypocalcemia in office practice. PMID- 1294512 TI - Urinary tract infections in the 90s: pathogenesis and management. AB - Urinary tract infections are one of the most common types of infection encountered in the practice of medicine. Recent discussions have focused on our current knowledge of natural host defenses that function during normal physiologic conditions in an attempt to prevent urinary infections. However, increased susceptibility to these infections may result from intrinsic risk factors that alter host defenses, or from extrinsic risk factors. Advances in the treatment of urinary infections have focused on short course therapy for women with uncomplicated lower tract infections, and on oral therapy in women with mild acute uncomplicated pyelonephritis. Also, in the area of prevention, reasonable candidates for antimicrobial prophylaxis have been identified. Even so, further studies are needed to define more clearly our understanding of the pathogenesis, treatment, and prevention of infections of the urinary tract. PMID- 1294513 TI - Criteria for diagnosis of urinary tract infection and evaluation of therapy. AB - Patients with urinary tract infections are commonly used to study the efficacy of new antibiotics. Some criteria, for example the presence of more than 100,000 organisms of a single species per ml as an indicator of infections, have been accepted for many years but all rules have exceptions. Other criteria such as relapse, re-infection are less clearly agreed. Furthermore, timing of collection of specimens during and after treatment shows great variation in protocols and in definition. These criteria and the methodology of collecting, transportation and examination of urine are discussed. PMID- 1294514 TI - Urinary tract infection in the elderly. How to treat and when? AB - The prevalence of urinary infection increases with increasing age for both men and women, reaching over 50% for both sexes amongst institutionalized patients. Bacteriuria is, generally, asymptomatic, and asymptomatic bacteriuria is not an indication for therapy, except prior to invasive genitourinary procedures. Treatment has not been shown to prevent subsequent symptomatic episodes, is associated with antimicrobial adverse effects, and promotes the emergence of resistant organisms. In addition, early recurrence is the rule following therapy in the institutionalized elderly and prolonged periods free of bacteriuria are seldom achieved. Symptomatic infection may manifest as invasive infection or irritative symptoms. Antimicrobial therapy is selected on the basis of organism susceptibility and patient tolerance. Therapy of 7-14 days is suggested, as short course therapy is not as effective in older women. For men, initial courses of therapy of 7-14 days are likely to be appropriate. As prostatic localization is frequent, recurrent symptomatic infection may require more prolonged therapy of six or 12 weeks. Bacteriuria in the elderly is a large and complex problem. Overuse of antimicrobials should be avoided, but further investigations to characterize the optimal use of antimicrobials are still required. PMID- 1294516 TI - Controversies in single dose therapy of acute uncomplicated urinary tract infections in women. PMID- 1294515 TI - Optimal characteristics of agents to treat uncomplicated urinary tract infections. AB - The optimal characteristics of agents to treat uncomplicated urinary tract infection must include activity against the major pathogens involved in these infections as well as a low potential for development of bacterial resistance. High urinary levels should be present for an adequate period to eliminate the organisms. Side effects should be minimal with minimal effect on the bacterial flora of the community. Treatment programs of single-dose, three days, or five days can be developed depending upon the agent. PMID- 1294517 TI - Single dose treatment failure in women with acute cystitis. AB - Single dose treatment regimens (SDT) are effective, inexpensive alternatives to longer courses of therapy for adult females with acute cystitis or asymptomatic bacteriuria. A number of SDT regimens consistently cure 85 to 100% of women with acute cystitis and 50 to 80% of women with asymptomatic bacteriuria. However, SDT is inherently less effective than longer regimens because many upper tract infections are not cured. Initial SDT studies suggested that most patients with significant renal invasive disease or underlying urological abnormalities fail therapy. As a result, SDT has been proposed as an efficient strategy to diagnose significant upper tract infections with accompanying pathology that merit additional investigation or treatment. Few studies have refuted or supported this hypothesis. Single-dose treatment studies show an association between the site of infection as determined by the antibody-coated bacteria (ACB) test and treatment outcome. Patients with ACB-negative tests have a cure rate of over 90% in almost all studies in which the organism is susceptible to the agent chosen. Patients with positive ACB tests tend to have treatment failure rates of 30 to 50%. However, imaging studies have not been carried out in parallel with these studies and the validity of using single-dose treatment failure to screen women for significant upper tract pathology has still not been established. PMID- 1294519 TI - Short-term treatment of urinary tract infections: the French concept. AB - The indications for short-term treatment to cure urinary tract infections (UTIs) have been recently clarified in France by a "Consensus Conference". Short-term treatment essentially concerns young, non-pregnant women with symptomatic uncomplicated lower UTI of less than three days duration, with no other underlying severe illness or previous uro-nephrological history, and who accept the idea of clinical and possibly bacteriological control after treatment. Only antibiotics with prolonged urinary excretion are recommended, i.e. co trimoxazole, fluoroquinolones or fosfomycin-trometamol. In pregnancy, in children, or in the elderly, indications for short-term treatment still remain controversial. As compared with conventional therapeutic strategies using urine cultures, the use of test strips for nitrite and leukocyte esterase for deciding on treatment and assessing its efficacy should allow considerable financial savings. PMID- 1294518 TI - Management of urinary tract infections in pregnancy: a review with comments on single dose therapy. AB - Most investigators agree that the adverse effects of urinary tract infections in pregnancy can be abrogated by effective early detection and treatment. However, the optimal methods for screening and treatment remain controversial. Although single-dose therapy has not been applied to pregnant women with acute pyelonephritis, most but not all studies which have compared single-dose with longer courses of beta-lactam or other antibiotics in pregnant asymptomatic bacteriuric women have shown no differences in outcome. This paper reviews recent trials of single-dose treatment of bacteriuria in pregnant women. PMID- 1294520 TI - Susceptibility of frequent urinary pathogens to fosfomycin trometamol and eight other antibiotics: results of an Italian multicenter survey. AB - In order to assess the resistance profile for fosfomycin trometamol after several years of clinical use in Italy, this study has explored the susceptibility to fosfomycin and eight other antibacterial drugs of 6,021 strains isolated from 23,816 urines during 1990 in three teaching hospitals located in Genoa, Parma and Catania. Gram-negative strains, notably Escherichia coli (41.6%), were primarily involved. Amoxicillin was the least active compound with resistance in 41.4% of the isolates. Fosfomycin showed the lowest rate of resistance in both gram negative (2.8%) and gram-positive (2.1%) pathogens. This was followed by norfloxacin with a resistance rate of 11.8% and netilmicin with 12.2%. These results indicate that fosfomycin-trometamol may continue to be used in single dose treatment of urinary tract infections even in the absence of microbiological data since the prevalence of resistance to the drug is, at present, so low that therapeutic failure is highly improbable. PMID- 1294521 TI - Spectrum and susceptibility of pathogens causing acute uncomplicated lower UTI in females and its correlation to bacteriologic outcome after single dose therapy with fosfomycin trometamol versus ofloxacin/co-trimoxazole. AB - In a multicentric study comparing oral single-dose therapy of fosfomycin trometamol (3 g as fosfomycin) versus co-trimoxazole (1.92 g) or ofloxacin (200 mg) as many as possible of the pathogens were sent to and analysed in a central laboratory. The pathogens were identified and minimal inhibitory concentrations (MIC) of fosfomycin, trimethoprim alone and in combination with sulfamethoxazole, ofloxacin, ampicillin, amoxicillin combined with clavulanic acid, and cephadroxil were determined. The eradication of pathogens (cfu < 10(3)/ml at one week after single-dose therapy) was analysed according to species and MIC of the antibiotic used. Urine cultures of 349 patients were analysed. Escherichia coli was the predominating species followed by staphylococci and Proteus mirabilis. Enterococci were mostly found in mixed culture. Baseline pathogens of monoinfections were eradicated in 87.1%, in 88.9% and in 86.4% of 284 patients treated with fosfomycin trometamol, co-trimoxazole and ofloxacin, respectively. The MICs of the five antibacterial agents and the two antibiotic combinations for 253 baseline pathogens showed that of the E. coli strains none was resistant to ofloxacin, three (MIC = 128 mg/l) were resistant to fosfomycin, 3.6% to co trimoxazole, 6.2% to trimethoprim, 8.8% to ampicillin, and 5.7% to amoxicillin/clavulanic acid. The eradication rates according to the MICs of the corresponding drugs showed equally good eradication rates for fosfomycin up to an MIC of 64 mg/l. Above this level two out of three strains were also eradicated by fosfomycin trometamol. For co-trimoxazole and ofloxacin no intermediately sensitive or resistant strains were found. Within the range of MICs found there were equally good eradication rates for both antibacterial agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294522 TI - The comparative activity of fosfomycin trometamol against organisms isolated from infected urines. AB - Five hundred urinary pathogens, collected from patients of general practitioners and hospital in-patients, were identified and tested for susceptibility to fosfomycin, ampicillin, cephalexin, nalidixic acid, nitrofurantoin, trimethoprim and sulfamethoxazole. Overall, 83% of the isolates were sensitive to fosfomycin, comprising 89% of the out-patient strains and 77% of the in-patient isolates. This degree of sensitivity was similar to that of cephalexin, nalidixic acid and trimethoprim, but higher than that observed with ampicillin, nitrofurantoin and sulfamethoxazole. Fosfomycin generally showed a broad spectrum of activity, but was less active than some other compounds against Klebsiella spp. and streptococci. More than 70% of strains resistant to ampicillin, sulfamethoxazole or trimethoprim were sensitive to fosfomycin indicating that cross resistance is not presently a problem. PMID- 1294523 TI - The influence of anaerobiosis on the activity of fosfomycin trometamol. AB - MICs of fosfomycin trometamol were estimated for 40 strains of bacteria (20 gram positive cocci, 20 gram-negative bacilli) by the agar incorporation method (Iso Sensitest agar) in the presence of the potentiating agent, glucose-6-phosphate (25 mg/l). Titrations were carried out in duplicate under aerobic and anaerobic conditions. For 22 strains (12 gram-negative bacilli), a fourfold or greater reduction in MIC was observed in tests conducted under anaerobic conditions. The effect was particularly marked with Klebsiella spp., four of five strains of which showed a 16- to 32-fold reduction in MIC in anaerobic conditions. To investigate the reasons for the effect of anaerobiosis, selected strains were examined in an opacity monitoring device in which cultures can be grown in aerobic or anaerobic atmosphere. Surprisingly, the effect of anaerobiosis observed by continuous turbidimetric monitoring was much less than that seen in agar incorporation MIC titrations: under anaerobic conditions, there was little or no reduction in the concentration of fosfomycin trometamol required to cause a lytic effect on dense bacterial cultures, and a small, but variable effect on the emergence of resistant variants. PMID- 1294524 TI - Fosfomycin trometamol in treatment of uncomplicated lower urinary tract infections in adult women--an overview. PMID- 1294525 TI - Treatment of bacteriuria in pregnancy with single dose fosfomycin trometamol: a review. AB - Bacteriuria in pregnancy occurs in about one in 20 pregnant women and is usually initially asymptomatic. It is an important marker for acute symptomatic infection (often pyelonephritis) later in pregnancy, which occurs in about one in four bacteriurics. Several considerations surround the antibiotic treatment of the asymptomatic infection; these include a low frequency of in vitro resistance to the agent used, lack of toxicity to the foetus, a low incidence of gastrointestinal side effects, good compliance and proven efficacy. Fosfomycin trometamol seems to fit these requirements. In three controlled studies (two multicentric) 250 patients were treated with fosfomycin trometamol in a 3 g (as fosfomycin) single dose; 197 patients were given one of three other agents. Cure rates for fosfomycin trometamol were 77-94% (68-94% for other agents), which was satisfactory in an infection which is sometimes difficult to eradicate. Further studies are needed in this important but accessible group of patients. Opportunities should be taken to study more foetal outcomes and provide more data on gastro-intestinal tolerability. PMID- 1294526 TI - The role of fosfomycin trometamol in the management of urinary tract infections in pediatrics. AB - Single-dose therapy has been documented in defined groups of adults. For children, this type of treatment requires further investigation. Children to be studied should have uncomplicated UTI and the drugs should optimally have a broad antibacterial spectrum, a low tendency to select for resistant bacteria, and pharmacokinetic properties allowing maintenance of inhibitory antibiotic levels in urine for at least two to three days. Fosfomycin trometamol, trimethoprim and co-trimoxazole are oral antibacterials that may prove effective for single-dose therapy in children, as has been suggested in some studies. PMID- 1294527 TI - Oral prophylaxis with fosfomycin trometamol in transurethral prostatectomy and urological maneuvers: literature review and personal experience. AB - In the literature there are three comparative and two open studies in which 1,395 patients received 3 g of fosfomycin trometamol per os 12 or three hours before and 24 hours after surgery: 625 patients received control substances or placebo. In the comparative studies the incidence of postoperative bacteriuria in patients treated with fosfomycin trometamol ranged from 2.9 to 7.6% at one week and from 1.2 to 3.2% at two to four weeks follow-up, and was lower than in patients treated with reference drugs or placebo. In the open study, postoperative bacteriuria ranged from 2.9 to 6.0% at one week follow-up. In our open study, 70 patients were evaluable. Four out of 70 (5.7%) developed fever > or = 38 degrees C, with positive urine culture, during the first three postoperative days. At two weeks follow-up another 5.7% showed a symptomatic urinary tract infection with a cumulative infection rate of 11.4%. In all cases, the bacteria were resistant to fosfomycin trometamol. A low incidence, 4.2%, of side effects, mainly related to the gastrointestinal tract, was observed. Fosfomycin trometamol proved to be effective with the advantage of no risk of cross resistance, practical pharmaceutical formulation with good patient compliance, good safety profile with few side effects and a satisfactory cost/benefit ratio. PMID- 1294528 TI - [Diuretic therapy: renaissance of time-tested therapeutic principles]. PMID- 1294529 TI - Induction of an invasive phenotype in benign tumor cells with a laminin A-chain synthetic peptide. AB - K-1735 clones 10 and M2 are cell lines cloned from a UV-induced murine melanoma. While both lines are highly tumorigenic, only the M2 cells are highly invasive in vitro and metastatic in vivo. Here we have exposed the clone 10 cells to the synthetic peptide PA22-2, which contains the IKVAV sequence from the A chain of laminin and which, like laminin, induces collagenase IV production and enhances metastasis formation by B16F10 cells. Zymogram analysis of conditioned media from clone 10 cells cultured on the peptide demonstrated a dose-dependent increase in collagenase IV activity. When clone 10 cells were cultured on a reconstituted basement membrane (Matrigel), this peptide caused an invasive phenotype comparable to the M2 cells. The invasive clone 10 cells were, however, unable to form lung colonies in vivo in the presence of this peptide. We conclude that this peptide represents an active site on laminin which is able to stimulate the invasiveness of this tumor cell line, but that this activity is not sufficient to confer metastatic potential. PMID- 1294531 TI - Altered establishment/clearance mechanisms during experimental micrometastasis with live and/or disabled bacterial lacZ-tagged tumor cells. AB - To study micrometastasis at its earliest stages, the bacterial lacZ marker gene was introduced into human EJ Ha-ras-transformed BALB/c 3T3 cells (LZEJ), followed by their intravenous injection into nude mice. Lung micrometastases were easily identified by blue staining of lacZ-tagged cells minutes/hours after injection, permitting effective evaluation of establishment/clearance mechanisms of LZEJ cells. Different treatments were used to disable LZEJ cells (fixation, irradiation, or mitomycin C) to determine modulation of these processes--although unable to divide, these cells stain for lacZ expression for days after treatment. Fixation-killed cells generated large microfoci (> 13-15 cells/focus) with well rounded morphologies while live, irradiated, or mitomycin-treated cells generated smaller, irregularly shaped foci (3-7 cells/focus). Fixed-cell foci were cleared more slowly from lungs than the other three classes, even when prefiltered to remove large aggregates. All foci of disabled cells were eventually cleared while a basal level of live-cell foci persisted. Co-injection of fixed and live cells (or preinjection of fixed cells, followed by live cells) resulted in complete clearance of live-cell microfoci; in contrast, preinjection of live cells (then injection of fixed cells) led to survival of live-cell micrometastases. Therefore, altered deformability and/or cell surface interactions of tumor cells modulate the effectiveness of host-clearing mechanisms in the lung and in some situations these altered cells facilitate clearance of live tumor cells that are normally tumor-progressing. PMID- 1294530 TI - Evaluation of in vitro reconstituted basement membrane assay to assess the invasiveness of tumor cells. AB - The crossing of tumor cells through basement membranes represents a critical step in the metastatic process. We have used a reconstituted basement membrane (matrigel) coated on filter in a Boyden chamber to assess the invasive potential of tumor and normal cells. No correlation was found between chemoinvasion in vitro and the metastatic potential in vivo. Normal human fibroblasts and murine 3T3 fibroblasts penetrated filters coated with matrigel. On the other hand, the tumoral cells (MCF7, MCF7 gpt, MCF7 ras, BeWo, JAR, NUC-1 cells) were unable to cross the matrix. Our results suggest that in our conditions, this widely used model to assess tumoral invasion does not provide a universal assay to test the invasiveness of tumor cells. Penetration of the matrigel appears to be related to chemotactic or haptotactic responses depending upon cell types. Our data emphasize the variability of molecular events associated with basement membrane invasion. PMID- 1294532 TI - MHC class I antigen expression is inversely related with tumor malignancy and ras oncogene product (p21ras) levels in human breast tumors. AB - MHC class I antigens participate in the immune response by presenting peptides to CD8+ cytotoxic T cells. Decreased expression of these antigens in tumor cells may contribute to an evasion of immune system and consequently to enhanced tumor growth. However, not all tumors expressing low levels of HLA antigens show increased malignancy, probably as a result of the differential activity of the oncogenes involved in malignant transformation. The ras family of cellular oncogenes is one of the most frequently detected families of transformation inducing genes in human solid tumors. The aim of this work is to study the expression of MHC antigens and the ras oncogene product, p21ras, in 60 primary breast tumors in order to define its clinical significance in tumor progression. HLA antigen expression and p21ras levels were measured on breast tumors using immunohistochemistry methods and enzymoimmunoassay, respectively. The results demonstrate that more invasive tumors have both a decreased expression of HLA class I antigens and higher levels of p21ras protein expression than less aggressive tumors. These findings indicate that the capacity of breast cancers to grow and metastasize is related to low levels of MHC class I antigens and enhanced p21ras expression, thus supporting the involvement of MHC and ras oncogenes in breast tumor malignancy. PMID- 1294533 TI - Polyclonal natural antitumor antibody binding dynamics: preferential release of surface membrane molecules and increased metastasis. AB - Flow cytometry revealed the dynamic nature of polyclonal whole serum naturally occurring IgG and IgM antibody binding to the syngeneic murine T cell lymphomas SL2-5, L5178Y-F9 and the in vitro selected high natural antibody binding variant L5178Y-F9 TPA/NAb+3. This was particularly evident at physiological conditions where the temperature was 37 degrees C and the concentration of reactive serum natural antibodies (NAb) was high. Lower binding was observed at 37 versus 4 degrees C, or after raising the temperature from 4 to 37 degrees C, a procedure which was associated with an augmented loss of 125I-surface-labelled material from cells incubated in NAb compared to cells exposed to growth media. Even at 4 degrees C, NAb binding exhibited biphasic kinetics suggesting a loss of surface bound NAb and a subsequent cycle of NAb uptake. The increased intravenous liver metastasis potential of the high NAb binding L5178Y-F9 TPA/NAb+3 corresponded with its higher total loss of 125I-surface-labelled material when incubated in NAb at 37 degrees C, and with its extensive loss of NAb binding when the temperature was raised from 4 to 37 degrees C. These observations are consistent with the idea that molecules released from the cell may contribute to the higher metastasis. This thinking was supported by the increased metastasis of tumor cells injected intravenously, either with serum in which they had been preincubated at 37 degrees C or into mice treated with supernatants from tumor cells incubated in NAb. PMID- 1294534 TI - [Wound healing disorders]. PMID- 1294535 TI - A price worth paying? PMID- 1294536 TI - Defend the weak. PMID- 1294537 TI - School health. Swings and roundabouts. PMID- 1294538 TI - School nurses immunising without a doctor present. AB - Oxfordshire's school health nurses routinely carry out rubella and tetanus and polio booster immunisations without a doctor present. Kate Saffin describes the preparation for and introduction of the practice and the results of an evaluation study. School nurses surveyed reported only one problem: increased workload because the doctor is no longer there to provide 'an extra pair of hands'. PMID- 1294539 TI - HIV/AIDS and sexual health. AB - In including HIV/Aids and sexual health as key areas, The health of the nation stresses that 'good personal and sexual relationships can actively promote health and well-being'. This is a central concept, presenting challenges for professionals working in education and health writes Doreen E Massey, director of the Family Planning Association. In the second of our series on the opportunities the white paper offers nurses working in the community, she explores some of these challenges; in particular that promoting sexual health is not simply about disease prevention. PMID- 1294540 TI - Health care interviews by school nurses. AB - A health care interview (HCI) carried out by school nurses was piloted in Bath health authority for pupils entering secondary school. Tim Williamson reports the results of an evaluation study involving 99 pupils who had previously had a check with the school doctor at the age of ten. The HCI significantly improved the children's knowledge of who the school nurse was and how to contact her, but failed to improve knowledge of what the school nurse did. A total of 39 problems requiring some action were identified. PMID- 1294541 TI - A village school perspective. PMID- 1294542 TI - What's cooking in school meals? AB - School meals are a valuable opportunity to provide children with a nutritious meal and to teach children about healthy eating. It is a service on which many children, and parents, still rely. Since 1980, however, school meals have not had to meet any minimum nutritional standards and the service has become increasingly cost-orientated due to budget constraints. Gill Cawdron looks at the school nurse's role in relation to two initiatives in school meals: the School Meals Campaign and the School Meals Assessment Project. PMID- 1294543 TI - Marketing: Part 4 of 4. Using quality assurance to promote the generic role. AB - Unless customers--purchasers, providers and the public--can identify the benefits of the health visiting service they are unlikely to see it as a priority provision, warns Joy Notter. In the fourth and final article in this series, she examines the role of quality and quality assurance in a marketing strategy to sell health visiting services. PMID- 1294544 TI - First aid. Helping them to help each other. PMID- 1294545 TI - Income support. Paths to receiving premiums. PMID- 1294547 TI - Miners. 'I'd rather Christmas were cancelled'. PMID- 1294546 TI - Rough justice. PMID- 1294548 TI - South East Thames. No safe haven. PMID- 1294549 TI - Beating the big killer. PMID- 1294550 TI - Family and social issues in sickle cell disease. AB - Sickle cell disease (SCD) in Britain affects some 150 babies a year, born mainly to Afro-Caribbean and West African families. Like every chronic illness, it can have major psychosocial and practical consequences. Kenny Midence and Polly Shand describe the condition and the problems facing people with SCD and their families. PMID- 1294551 TI - Informal care: problem or solution? AB - Government policy stresses that care in the community must mean care by the community. Government policies have increasingly recognised, too, that care by the community means care by families. Yet social support policies have reduced the benefits available to carers. Hilary Graham examines the problems facing those giving and seeking informal care. PMID- 1294553 TI - Understanding what they tell us. PMID- 1294552 TI - War and community health in the Philippines. PMID- 1294554 TI - Starting a gentle exercise class for the elderly. PMID- 1294555 TI - GP fundholding. Sold out to slow extinction. PMID- 1294556 TI - The Birth Traditions Survival Bank. PMID- 1294557 TI - Propranolol retards revascularisation and impedes early myogenesis in regenerating skeletal muscle transplants: an autoradiographic and morphometric study in mice. AB - The beta-antagonist (blocker) propranolol was tested for its effects on satellite cell proliferation and the revascularisation and regeneration of transplanted skeletal muscles. Utilising autoradiographic techniques it was found that there was no difference in the actual timing of onset of satellite cell activation between propranolol-treated and control mice. However, the numbers of proliferating myogenic cells were substantially reduced in the propranolol treated mice until revascularisation of these transplants began, about 24 h later than in the controls; myogenesis was therefore retarded by propranolol. When transplants from propranolol-treated and control mice which had been allowed to regenerate for 14 d were analysed morphometrically it was found that there was no significant difference in the size of the transplants, although propranolol induced the formation of substantial lipid deposition in the central transplant region; this was evidence of inhibited revascularisation in the early stages (up to 4 d) after transplantation. PMID- 1294559 TI - Cartilage and related tissues in the trunk and fins of teleosts. AB - The structure and distribution of cartilage and related tissues in the dorsal fin, caudal fin and vertebrae of teleosts were studied in 11 species. With the exception of Zellknorpel, all the tissues previously described in teleost heads were present in the trunk and fins, although they were found in smaller quantities. The distribution of the supporting tissues indicates that they serve different functions. Hyaline cartilage was restricted to vertebral and fin bones undergoing endochondral ossification, fibro/cell-rich cartilage acted as an articular tissue, and hyaline-cell cartilage and its subtypes formed flexible and resilient supports in the caudal fin. Mucous connective tissue was packed as a space-filler around neurovascular bundles in fin rays, and chondroid bone was found beneath articular surfaces. The differences between cranial, and trunk and fin supporting tissues may reflect developmental as well as functional differences between the cranial and postcranial skeleton. PMID- 1294558 TI - Hypertrophy of rat extensor digitorum longus muscle injected with bupivacaine. A sequential histochemical, immunohistochemical, histological and morphometric study. AB - Histochemical, immunohistochemical, histological and morphometric properties of bupivacaine-injected rat skeletal muscle were studied at times spanning the complete course of degeneration and regeneration to establish when, if ever, 'normality' is reached. This was achieved in a sequence of measurements made on the same series of rat fast-twitch extensor digitorum longus muscle (EDL), of the fibre type composition, myosin heavy chain content, fibre size, connective tissue content and myofibril size at 1-2 h and 2, 4, 8, 11, 21, 40, 60, 80 and 180 d after treatment. By 2 d after injection 86% of the fibres had undergone necrosis. A rapid restoration of histochemical, immunohistochemical and morphometric properties then occurred, being apparently complete by 21 d after injection. A pattern of ongoing changes recognised when regeneration was essentially 'complete' are reminiscent of changes that occur in muscles following compensatory hypertrophy produced by synergist ablation. These changes included an increase in muscle weight, a decline in normalised peak twitch and tetanic tensions, and normalised force in response to different stimulation frequencies (Rosenblatt, 1992), an increase in the relative number of type I fibres and of fibres reacting with the slow myosin heavy chain antibody, an increase in whole muscle cross-sectional area, an increase in type I and type II fibre cross sectional area and diameter, an increase in myofibril cross-sectional area, density, number, and area fraction, and an increase in the relative proportion of intramuscular connective tissue collagen. This suggests that the EDL muscle is being made to do more active work and is being influenced by passive forces (stretch) imposed on it. These changes appeared permanent: they stabilised at about 60 d after injection and were maintained for at least the next 120 d. PMID- 1294560 TI - Macrophages and other endocytic cells in the mouse uterus during the second half of pregnancy and into the postpartum period. AB - The spatiotemporal distribution of macrophages in the uterine wall of mice in the second half of pregnancy and the early postpartum period has been studied. Macrophages were identified using a combination of morphological criteria, the capacity to endocytose horseradish peroxidase and the expression of the Mac-1 antigen. Macrophages were a consistent feature of the myometrium. Numerous endocytic cells were found in the decidua basalis and metrial gland of pregnant mice and in the 'scar' regions of postpartum mice. However, few of the endocytic cells expressed the Mac-1 antigen. It is concluded that stromal/decidual cells, and not monocyte-derived macrophages, are primarily responsible for the removal of cellular debris in the decidua basalis and metrial gland during the last week of pregnancy and in repair of the uterine wall in the postpartum period. PMID- 1294561 TI - Lectin histochemical study of the prostate gland of the rhesus monkey (Macaca mulatta). AB - Glycoconjugates in the secretory epithelial cells of the rhesus monkey (Macaca mulatta) prostate gland were investigated using lectin histochemistry. The monkey prostate possesses cranial and caudal lobes. Histochemical staining with a battery of 8 lectins demonstrated differences in lectin binding patterns of the secretory epithelial cells between the 2 lobes. BS-1 bound exclusively to the cranial lobe, and PNA bound exclusively to the caudal lobe. DBA bound exclusively to a number of the secretory epithelial cells of the caudal lobe. In addition, both lobes showed binding with Con-A, RCA-1, WGA and S-WGA, but were negative for binding with SBA. Specific lectin binding patterns suggest a differing carbohydrate composition for each region, and a biological difference between the cranial and caudal lobes of the rhesus monkey prostate. PMID- 1294562 TI - Mandibulodental allometry in the African wild dog, Lycaon pictus. AB - Mandibulodental relations were evaluated in a sample of 34 adult Lycaon pictus crania (18 males, 16 females). Standard mesiodistal and buccolingual measurements, together with 8 mandibular measurements (intercondylar distance, intercarnassial breadth, mandibular length, arch length, condylar height, canine condylar length, mandibular width, mandibular height) were allometrically scaled to total skull length. These results were then compared with those of domestic dogs and of 3 smaller southern African canids, Vulpes chama, Canis adustus and C. mesomelas. The results highlighted the differences in mandibulodental relations between males and females and provided support for the theory that females have relatively larger postcanine tooth sizes to match the higher masticatory demands of lactation and pregnancy. The African wild dog is shown to be more closely related dentally to the domestic dog than has previously been supposed. PMID- 1294563 TI - The proboscis in human cyclopia: an anatomical study in two dimensions. AB - A 2-dimensional anatomical study has been undertaken of the proboscis and its contribution to the roof of the median orbit in human cyclopia. The cyclops material consists of 4 sectioned fetal heads and a dried cyclops skull. The skeleton of the proboscis is formed by the nasal capsule. The base of the proboscis lies in the floor of the anterior cranial fossa filling an extended ethmoidal notch and contributing to the roof of the median orbit anterior to the fused lesser wings of sphenoid. The cavity of the proboscis is lined with squamous epithelium, respiratory and olfactory mucosa. Olfactory fibres pass from the proboscis into the extradural space of the ethmoidal notch forming a collection of tissue similar to the inferior layer of the normal olfactory bulb. The data indicate that the proboscis represents the anterosuperior part of the normal nasal cavity developed in the absence of median components. It is suggested that the cyclops face constitutes a model for the study of the development of the normal face. PMID- 1294564 TI - A further study of the high incidence of the median artery of the forearm in Southern Africa. AB - Sixty-two forearms from 36 cadavers of South Africans of European extraction were dissected. The frequency of the median artery per forearm was 27.4%. There was neither bilateral difference nor sexual dimorphism in the incidence of the artery. These findings compare well with a previous study of black South Africans (Henneberg & George, 1992) where frequency per forearm was 27.1%. Our findings are much higher than those of earlier studies. This discrepancy may be explained either by differences in the thoroughness of the observations or regional variation, or by the occurrence of a secular trend in the development of vasculature. PMID- 1294565 TI - Significance of the innervation pattern of the human abductor pollicis longus muscle. AB - The abductor pollicis longus muscle (APL) can be separated into 2 divisions, deep and superficial. The deep division has more bellies, each of which has its own site of insertion. The superficial division is situated on top of the deep tendon. Each division is innervated by a separate branch of the radial nerve. This pattern of innervation may indicate independent actions by individual muscle parts. The deep division, inserting around the carpometacarpal joint of the thumb, has a nerve supply that reaches each separate muscle belly. This division should have a stabilising action on the joint. The superficial division, together with the extensor pollicis brevis, is innervated from the ulnar side by a terminal branch of the radial nerve. This division should, in cooperation with the extensor pollicis brevis and longus muscles and the thenar muscles, act to move the thumb in various directions. PMID- 1294566 TI - Neuropeptide accretions in the endoplasmic reticulum of oxytocinergic neurons in cats, monkeys and rabbits: a widespread phenomenon. AB - Light microscopic observations using Nomarski optics on the aldehyde-fixed hypothalamus of normal adult cats, monkeys and rabbits revealed the presence of cells in the supraoptic, paraventricular and periventricular nuclei which possessed yellow birefringent inclusions. Immunogold labelling showed that in each species the cells displayed oxytocin-like immunoreactivity, both in electron dense inclusions within some (but not all) cisterns of rough endoplasmic reticulum and in secretory granules. The cells in cats and rabbits were in all respects indistinguishable from the homologous 'birefringent' cells previously described in rats, but in monkeys, cells frequently contained additional inclusions in cisterns of rough endoplasmic reticulum which did not display oxytocin or vasopressin-like immunoreactivity, even after trypsin, pepsin or chymotrypsin treatment of sections. Observations on cats and rabbits using fluorescence microscopy revealed that the birefringent cells possessed bright autofluorescence which facilitated the identification of more cells than were seen using Nomarski optics alone. Autofluorescence was abolished when sections were mounted in glycerol, or when exposed to light for protracted periods of time. Attempts to label for monoamines in these cells were not successful, suggesting that the fluorescence is not due to aldehyde-induced amine fluorescence. It is not clear why neuropeptides are retained in some rough endoplasmic reticulum cisterns. It is possible that these birefringent cells contain a peptide, or peptides, which are abnormal in some manner, or which may be other members of the oxytocin gene family. Alternatively, the processing of neuropeptides to permit their export to the Golgi apparatus may be deficient. Acetylcholinesterase (AChE) histochemistry revealed that, unlike other oxytocin neurons, cells with intracellular accretions lacked detectable acetyl cholinesterase. As AChE is a known peptidase, it may be involved in regulating peptide export from the rough endoplasmic reticulum. PMID- 1294567 TI - M. J. T. FitzGerald: undergraduate medical anatomy teaching: Journal of Anatomy (1992) 180, 203-209. PMID- 1294568 TI - A permeability barrier to lanthanum and the presence of collagen between odontoblasts in pig molars. AB - Previous experiments in rat incisors indicate that the odontoblasts form an impermeable barrier which prevents fluid movement between pulp and dentine. The permeability of the odontoblast layer has now been investigated in pig molars which are more analogous to human teeth. The heads and necks of anesthetised piglets were perfused intra-arterially with lanthanum nitrate in Ringer's solution or with Ringer's solution alone. Molar tooth germs were removed, sliced, fixed by immersion and embedded in resin. Ultrathin sections including pulp and dentine were examined by transmission electron microscopy. Fenestrated capillaries were permeable to the electron dense lanthanum which thus entered the extracellular space between the odontoblast cell bodies. The lanthanum was excluded from predentine indicating that a barrier to permeability is present. In the above specimens and in others from 2 animals which were fixed by perfusion fixation, longitudinally oriented bundles of collagen fibrils were found passing from dentine through predentine into the odontoblast layer. Longitudinal collagen was also present between odontoblast cell bodies and entering the pulp at their basal ends. This suggests that classical von Korff fibres are present during primary circumpulpal dentinogenesis. In some sections longitudinally oriented collagen was absent. The junctions showed features of classical tight junctions but open tight junctions containing longitudinal collagen were also observed, suggesting that the junctions may modulate. Despite a trace of evidence that lanthanum can leak through adjacent to longitudinally penetrating collagen we concluded that the biological permeability barrier is maintained. The presence of the barrier indicates that other than the longitudinal collagen fibrils of which the source is unknown, all molecules incorporated into dentine are deposited there by the odontoblasts. An advantage of the barrier may be that it provides a closed environment for the orderly process of matrix deposition and mineralisation of dentine. PMID- 1294569 TI - Pericapillary collagen in the human thymus: implications for the concept of the 'blood-thymus' barrier. AB - The deposition of collagen in the walls of capillary-size blood vessels was studied in 95 human thymuses with respect to the site of deposition, extent of the change and relation to age and degree of involution. When examined by electron microscopy the collagen was found to be situated between the 2 basement membranes of the so-called 'double-layered' capillaries characteristic of the thymus of many species. This results in the formation of substantial 'collars' of collagen around a proportion of the blood vessels examined. Few such collars are seen before birth, but their number and thickness increase markedly during the 1st year of life. The relationship of these changes to the degree of involution is less apparent. The significance of these changes to thymic structure and function is discussed in relation to cell traffic through the thymus and the postulated 'blood-thymus barrier', the existence of which is seen to be in some doubt. PMID- 1294571 TI - Quantitative analysis of factors contributing to expansion of microvillous surface area in the coprodaeum of hens transferred to a low NaCl diet. AB - A stereological study of the lower intestine (coprodaeum) of the domestic hen was undertaken using combined light and electron microscopy. Numbers of columnar absorptive epithelial cells and the dimensions and numbers of microvilli were estimated. The aim was to identify the main factors contributing to an increase in microvillous surface area following transfer of hens from a high to a low NaCl diet on which they were kept for at least 3 wk. The principal contributor to observed changes between organs was cell number. Birds adapted to the low NaCl diet had 57% more cells than high NaCl controls. The average cell had a larger microvillous surface (55%) and this could be explained by the presence of longer (34%) and more densely packed (38%) microvilli. The total number of microvilli per coprodaeum doubled (from 35 x 10(9) on the high NaCl to 71 x 10(9) on the low NaCl diet). The increase in cell number accounted for 67% of the change in surface area and 78% of the change in number of microvilli per organ. These findings emphasise that, when assessing the form and function of a whole organ, it is important to monitor cell populations as well as single cells. This is especially true when studying renewing and expanding (rather than static) populations. PMID- 1294570 TI - Changes in fibronectin, laminin and type IV collagen distribution relate to basement membrane restructuring during the rat vibrissa follicle hair growth cycle. AB - Hair growth in adult mammals involves continuous dermal-epidermal interaction across the follicular basement membrane, and repeated reorganisation of lower follicle structure during the hair growth cycle. The immunolocalisation of 3 extracellular matrix components, fibronectin, laminin and type IV collagen was investigated during the course of the rat vibrissa follicle growth cycle, and their distribution correlated with changes in cellular and extracellular ultrastructure, particularly around the basement membrane zone. Laminin and type IV collagen were omnipresent at the follicular dermal-epidermal junction, but were also seen in granular extracellular form within the inner dermal component of the follicle, the dermal papilla. Both the inner papilla-epidermal junction and the thick specialised outer basement membrane (the glassy membrane) revealed labelling by these 2 antibodies around telogen (the period of nonfibre production). By contrast, fibronectin was abundant within the anagen dermal papilla but at telogen stained the dermal-epidermal junction heterogeneously, when it disappeared from the inner papilla-epidermal interface but intensified externally. These changes to extracellular matrix distribution coincided with a modification of basement membrane ultrastructure from a relatively uniform line at anagen, to one which became much broader and multilayered at telogen with a loss of definite structure within the papilla. This shows that the lower part of the vibrissa follicle retains the capacity for very rapid basement membrane modification and remodelling, and implies that it is part of the biological process which enables dermal-epidermal signalling, rather than a secondary product of physical changes to the appendage. The work supports the idea that dermal papilla cells could contribute to basement membrane formation, and also that fibronectin may be involved in regulating cellular activities within the follicle. In the vibrissa follicle, dynamic cellular activity clearly takes place throughout the duration of the hair cycle. PMID- 1294572 TI - Distribution of anionic sites on the perineurium. AB - The distribution of anionic sites on the perineurial basal lamina (BL) and plasmalemma of dorsal root ganglia and sciatic nerves was determined using cationic ferritin (CF) and cationic gold (CCG). The probes were applied to the tissue before and after resin embedding and visualised by electron microscopy. There were no apparent differences in charge distribution between the 2 tissues. At physiological pH a strong anionic charge was distributed evenly over the BL as demonstrated by pre-embedding labelling with CF; the plasmalemma was only moderately anionic. A similar application of CCG at pH 2.0 revealed a quasi regular distribution of anionic sites (presumably due to acidic carbohydrate moieties) on the BL, whilst CCG-labelling of L. R. White sections indicated a differential distribution of these moieties on the BL of the inner and outer perineurial lamellae. Cationic ferritin (12 nm diameter) crossed the BL and entered perineurial caveolae, but CCG (effective diameter of 15 nm) did not, suggesting that the BL is a size-restrictive filter. These results are discussed with regard to the ultrastructure and function of the BL of other tissues and the possible role of perineurial BL charge as a determinant of perineurial permeability. PMID- 1294573 TI - Microangioarchitecture of the guinea pig gallbladder and bile duct as studied by scanning electron microscopy of vascular corrosion casts. AB - The microvasculature of the gallbladder, the common bile duct, and the duodenal papilla was investigated in 20 albino guinea pigs (Cavia porcellus) using microvascular corrosion casting and scanning electron microscopy (SEM). Main supplying and draining vessels (first-order vessels) approach the gallbladder along the cystic duct. From the latter, penetrating vessels (second-order vessels) arise which pierce the muscular coat of the gallbladder body to form the plexus of third-order vessels between the muscle coat and the mucosa. Third-order vessels finally branch to supply the subepithelial capillaries, which show a honeycomb arrangement, corresponding to the gallbladder pits. At the areas bordering mucosal pits and beneath the tunicae plicae mucosae, the capillaries form glomera. These structures make the mucosal vasculature suitable for adapting to gallbladder wall distension caused by volume changes. The mucosal capillary glomera may also be involved in absorption of substances from bile, or they could act as buffer zones, counteracting the pressure which develops as the gallbladder volume increases. Venous sphincters occurring at the junction of mucosal vessels with the subjacent third-order veins may regulate blood flow in the mucosal glomera. The neck region as well as bile ducts consist of 2 vascular layers: an inner capillary layer and an outer one containing arterioles and venules. The duodenal papilla has a hemispheric shape and is interposed in the transition zone between the stomach and the duodenum. On the most luminal aspect, the capillaries of the papilla have a ring-shaped arrangement, as do the capillaries of the stomach, surrounding the mucosal glands; the remainder of the papilla is covered by duodenal villi capillaries. PMID- 1294574 TI - MR features of intracranial hemangioblastomas. AB - The contribution of MR in 10 patients with surgically proven intracranial hemangioblastomas was retrospectively evaluated and correlated with the computed tomographic findings. Angiography was obtained in eight cases. Multiple lesions were shown in only two patients, but none proved to have von Hippel-Lindau disease. In six patients the tumor typically appeared as a cystic lesion with an intensely enhancing mural nodule at the pial surface of the cyst; three patients presented with a solid lesion with a central cyst and one with a solid lesion only. Thirteen tumors were located in the posterior fossa, with one in the brain stem extending towards the spinal cord. A supratentorial localization was found in two patients. Abnormal serpiginous vessels supplying or draining the mural nodule or solid lesion were not visualized on contrast-enhanced computed tomography, but were easily identified as flow voids on MR in five patients. Calcification or hemorrhage were not seen in the entire series. Because of the multiplanar imaging capability and the lack of streak artifacts from the petrous bone, MR provides better localization than CT. MR is more accurate in predicting the number, extension and vascularity of hemangioblastomas, and provides a sound basis for further diagnostic and therapeutic procedures. PMID- 1294575 TI - Portal vein thrombosis after acute pancreatitis: diagnostic confirmation with computed tomography during arterial portography. AB - Portal vein thrombosis is a rare complication of pancreatic inflammatory disease. Usually, the radiologic diagnosis is made either by ultrasonography, contrast enhanced CT or angiography. Moreover, MRI seems a very promising method. CT during arterial portography (CTAP) focused on portal system proved to have a place in the evaluation of portal vein thrombosis in a particular case. PMID- 1294576 TI - Postoperative imaging of labyrinthine fistulae in cholesteatomas. AB - We evaluated the morphology of three operatively closed labyrinthine fistulae which were due to acquired middle ear cholesteatoma in three patients. In all three cases the fistula location was in the horizontal semicircular canal. The fistulae were closed by a mixture of bone powder and Tissucol. The layer closing the fistula was in all cases indistinguishable from the bony otic capsule on the postoperative CT. PMID- 1294577 TI - Arthro-CT in detecting sideways displacement of the temporomandibular joint disk. AB - One of the major disadvantages of sagittal arthrotomography of the temporomandibular joint is its limited capability to detect sideways (medial or lateral) disk displacement. Several arthrographic signs, suggesting sideways disk displacement have been described in recent reports. The most important one is the edge sign. In doubtful cases, arthro-CT can be used for depiction of medial or lateral disk displacement. PMID- 1294578 TI - Spontaneous rupture of the bladder: an uncommon finding on excretory urography. AB - A case of recurrent intraperitoneal bladder rupture is reported. Tearing occurred after minor trauma in a woman who had suffered a fracture of the pelvic rim 6 years earlier. Spontaneous rupture of the bladder is rare. The symptoms of an intraperitoneal bladder rupture may suggest intestinal disease and intravenous urography may be misleading. A retrograde cystogram is required to obtain the diagnosis. PMID- 1294579 TI - Chronic focal fibrosing pancreatitis: detection by MRI. AB - The study of a 70-year-old woman with fibrosing pancreatitis, an uncommon variety of chronic pancreatitis, presenting as a discrete solid mass in the head of the pancreas, is reported. CT and US were non-diagnostic while ERCP and MR detected a focal anomaly. This case report stresses the sensitivity of MR in some pancreatic pathologies. PMID- 1294580 TI - Congenital intrahepatic porto-systemic shunt. AB - An asymptomatic case of intrahepatic shunt between a portal and hepatic vein is presented. Ultrasound examination combined with Doppler sonography showed a communication between a dilated portal vein and a hepatic vein. Computed tomography and angiography confirmed the findings. Porto-hepatic venous shunting is very rare and has previously been reported in association with cirrhosis. The vascular malformation we present is believed to be a congenital anomaly, as no signs of cirrhosis or trauma were found. PMID- 1294581 TI - [Stomach adenocarcinoma: what form of gastrectomy?]. AB - Three hundred and sixty consecutive cases of gastric adenocarcinoma were studied retrospectively between 1976 and 1987. Surgery was curative in 195 patients: 91 had a subtotal gastrectomy 83 a total gastrectomy and 21 a proximal gastrectomy. Subtotal and total gastrectomy were compared within this group in terms of postoperative morbidity and mortality, abdominal comfort and 5-year actuarial survival: Postoperative mortality was greater after total gastrectomy (9.6 vs 2.2%, p = 0.04), as were anastomotic leaks (19 vs 2%, p = 0.0009). Mean weight loss was greater after total gastrectomy (p = 0.005). Comparison of patients with similar tumor staging and localization did not show any significant difference in 5-year actuarial survival. If subtotal gastrectomy is certainly justified for distal gastric cancer, it should be considered for some proximal localization. PMID- 1294582 TI - [Surgical silicone prostheses in the treatment of biliary tract cancers: long prostheses or short prostheses? Results apropos of 500 cases]. AB - The interest of surgical prostheses in the palliative treatment of biliary tract cancer is well established, on the basis of their good tolerance, the more than 15 year follow up experience and the number of patients operated upon. After exeresis, they allow re-establishment of continuity, either by use of a prosthesis in Y when the right and let ducts can be dissected, or by using two prostheses, a multiperforated long prosthesis reimplanted in the duodenum and a short prosthesis reimplanted in the common bile duct without attaining the sphincter of Oddi. Of the 1000 cases treated, 500 were the object of a statistical analysis, 46 being operated upon by the author, in 60% of cases for biliary tract cancer, either primary or as an extension from the gallbladder. One third of the patients had advanced lesions and a short survival of less than 3 months. Two-thirds a median survival of 9 months. In 10%, a radical exeresis was performed with survival of more than one year without recurrence of jaundice. Failure of treatment with persistence of jaundice was due to advanced disease for which surgery is unsatisfactory. Essential complications were premature bile leaks (5%) without serious consequences if sufficient drainage was maintained, since it stopped spontaneously, and angiocholitis (6%), the result of territory exclusion or reflux. Recurrence of jaundice was related to extension of the neoplasm to the secondary bile ducts, and to hepatic metastases. Obstruction of the prosthesis before two months was rare (6%) and was preceded by angiocholitis. In the absence of recurrence of the cancer the prosthesis can be replaced surgically without difficulty. PMID- 1294583 TI - [Should routine exploratory laparotomy be performed in the presence of an abdominal wound? Discussion apropos of 176 cases]. AB - Management of abdominal wounds is presently the subject of discussion between the partisans of routine laparotomy and those preferring "armed" surveillance. Results of study of a series of 176 abdominal wounds subjected to surgical dogma showed: that the diagnosis of non penetrating wounds (17.6%) was not always evident, due either to their anatomical localization (frontier region wounds) or to insufficient local exploration in urgent cases (6.6% of false-negatives), that the existence of serious clinical signs (50 cases) was always associated with one or more visceral lesions, requiring urgent laparotomy with a morbidity of 20% and a mortality of 8% (4 cases), that in the case of asymptomatic penetrating wounds (96 cases), routine laparotomy did nevertheless allow the diagnosis of visceral lesions in 50 cases (including 23 major lesions) but was of no utility in 46 cases (31.5% of blind laparotomies for the total series). The elevated proportion of useless laparotomies (30% in the literature), the result of a dogmatic attitude, or the risk of a delayed intervention (5 to 8%) in the series practising the selective method, led to a modification in the authors' attitude. The existence of serious signs should obviously result in a laparotomy. In their absence, and when confronted with a penetrating or doubtful (frontier region) wound, an exploratory celioscopy is proposed to ensure complete abdominal exploration, to confirm the presence or absence of penetration, to treat minimal lesions and to perform a classical laparotomy in case of evident necessity. PMID- 1294584 TI - [Paraplegia after surgery of the suprarenal aorta (26 cases reported during a national survey)]. AB - Although their frequency is probably underestimated, medullary complications of abdominal aorta surgery are rare but serious, and may be the cause of medico legal actions. Referral of a patient allowed the collection of 26 unpublished cases: 18 with aneurysms, including 6 ruptured lesions and 12 undergoing cold surgery, and 8 with aorto-iliac occlusion, these 26 cases representing 0.16% of abdominal aorta interventions performed during the same period. Mortality (6 cases) was due principally to neurological complications, total in 4 cases, partial in 3 and persistent in 13. Risk factors were perioperative collapse (explaining the elevated frequency in ruptured aneurysms) and the occlusion of the internal iliac arteries. Duration of clamping was not significant. No certain method of prevention could be elucidated, either by a literature review or by analysis of the personal series. PMID- 1294585 TI - [The aorto-esophageal fistula. A rare cause of digestive hemorrhage]. AB - The authors report a new case of aortoesophageal fistula caused by a giant ulcer of the esophagus. Success of the surgical treatment during the bleeding period couldn't occult the seriousness of this fistula which is almost fatal. Only an early diagnosis permitting a surgical treatment in better conditions could improve the prognosis of this condition. PMID- 1294586 TI - [Surgical treatment of ruptures of the achilles tendon in athletes. 31 cases operated on with an average follow up of 4 years]. AB - The authors analyze a series of 31 tendo achillis ruptures occurring after sport accident. All were treated surgically. The actual follow up being of 4 years (1 to 12 years). In nearly one third of the cases, either a change in the training methods or intensive activity was noted. 80% of cases showed an causal violent trauma. Tendinopathy preceded the rupture in 20% of the cases, without being an important prognosis factor. In 70% of cases, diagnosis was made within the 24 following hours, and later (more than 8 days after) in one patient out of ten. Type of the surgical procedure does not seem to make any change in the long term prognosis. Each time a severe post op. complication occurred, the final result was bad. In one third of cases pre op. and post op. tendon lengths were not identical, this detail not seeming to bother the patients. In 60% of cases, same sport level was reached. In 80% of cases the final results were good or excellent. PMID- 1294587 TI - [Metacarpophalangeal luxation of the thumb. Apropos of 30 cases]. AB - A retrospective study of a series of 30 cases of metacarpo-phalangeal luxation of thumb (18 dorsal and 12 palmar) showed the relatively high frequency of the palmar variety both in adults and children. Prognosis was better for dorsal than for palmar luxations, the latter being associated with other lesions; cutaneous, tendinous and/or bony, these constituting the severity factor. PMID- 1294588 TI - [Osteosynthesis of fractures of thr proximal end of the humerus by the screw-pin technique]. AB - Both fascicular pinning as described by Appril and palmate pinning are inconvenient in that the pins can perforate the articular cartilage of the humeral head and provoke premature unpinning because of insufficient fixing in an osteoporotic bone. A new osteosynthesis material has been developed to reduce these inconveniences: the screw-pin. This ensures initial stability in the humeral head and allows immediate postoperative re-education of displaced fractures of the upper end of humerus. Results are presented of the use of this new material since 1988 in 26 fractures of upper end of humerus. PMID- 1294589 TI - [Surgical treatment of carcinoid tumors of the intestine]. AB - Carcinoid tumours arise from the neuroendocrine system and present a characteristic morphological picture. They occur in almost every organ, predilected sites are the appendix and the small intestine. Prognosis depends on the primary localization and tumour size. Carcinoids of the appendix and rectum are mostly small and thus have a good prognosis. Growth of bronchial, stomach and small intestinal carcinoids is aggressive and implicates a high percentage of metastatic disease. First choice therapy is the surgical removal of the tumour. Depending on tumour size surgical treatment includes fulguration, local excision and oncologic radical resection up to extended organ extirpation. Reoperation and repeated surgery have good chances to be successful concerning tumour remission and improvement of the carcinoid syndrome. Additive treatment comprises in particular somatostatin therapy and, in some cases, chemotherapy. PMID- 1294591 TI - [Peritonitis caused by rupture of a mesenteric cyst]. PMID- 1294590 TI - [Angioma of the spleen]. PMID- 1294592 TI - [Chronic Corynebacterium endophthalmitis. Apropos of 3 cases]. AB - Only a few isolated cases of endophthalmitis have Corynebacterium been implicated as etiology. This diphtheroid, which has been considered for a long time as a nonpathogenic contaminant from the conjunctival flora, may produce systemic diseases usually in immuno-deficient patients. Keratitis and endophthalmitis cases have been reported in the literature. We report three cases of chronic endophthalmitis after extracapsular extraction with intraocular chamber posterior lens which are characterized by many subacute iridocyclitis and vitritis attacks treated by topical steroids. These endophthalmitis are characterized by decrease of visual acuity, hypopion, white plaque on posterior capsule and vitritis. In the first case, Corynebacterium has been isolated from the culture of vitreous and in the second and third cases from the culture of aqueous humor. These bacteria are often very slow growing, 8 to 14 days in the 3 cases. Colonies may not become visible on culture plates before one week or more. Corynebacterium grow well on ordinary media (blood and chocolate agar). The major difficulty is not to discard organism frequently considered contaminants. The treatment associated systemic antibiotherapy with steroids or not, central capsulotomy and vitrectomy with intraocular injection of antibiotic with or without steroids. Antibiotics sensitivities among diphteroids vary greatly. Quinolones, penicillins, vancomycin, cyclines and aminosides are often a good choice. However, individual sensitivities determined by the antibiogram must be used for an appropriate treatment. PMID- 1294593 TI - [Photorefractive keratectomy following undercorrected myopic epikeratoplasties]. AB - Five eyes had a delayed refractive regression following myopic epikeratoplasty; the undercorrection ranged between -8.00 and -10.00 diopters. Four of the 5 eyes had a loss of best spectacle visual acuity of two Snellen lines or more. Excimer laser photorefractive keratectomy was performed to achieve a full refractive correction. A dense subepithelial haze was observed in the 5 eyes. The 3 months postoperative refraction ranged between -1.00 D and +2.50 D but the spectacle corrected visual acuity reached only 0.1 to 0.2. Because of the poor visual acuity results, the five epikeratoplasty lenticles were removed, resulting in restoration of best preoperative spectacle visual acuity in 4 of the 5 eyes. Excimer laser photorefractive keratectomy was not a helpful means of correcting residual high myopia after myopic epikeratoplasty. The poor results may be explained by the preexisting stromal abnormalities. PMID- 1294594 TI - [Evaluation of the efficacy of antimicrobial drugs in ophthalmic solutions]. AB - The antimicrobial efficacy of preservatives in ophthalmic solutions was tested. Five strains were used as challenge organisms. They represented bacteria, yeasts and molds. Sixty per cent of the ophthalmic solutions showed a good preservation against S. aureus ATCC 6538, according to the standards and in 40% of cases, the bacteria disappeared on the second week. Against E. coli ATCC 8739, 90% of the samples were well preserved and in 10% the bacteria disappeared by the second week. Against Ps. aeruginosa ATCC 9027, C. Albicans ATCC 10231 and Asp. niger ATCC 16404, the ophthalmic solutions showed a 100% preservation. The majority of the products showed a satisfactory preservation. They contained declared preservatives and sometimes combinations of two antimicrobial agents. PMID- 1294595 TI - [Values and limitations of radioimmunoscintigraphy with MoAb 225-28S in the diagnosis of posterior uveal melanoma]. AB - When evaluating a clinical situation in which a posterior uveal melanoma (PUM) is suspected, we have to use all available diagnostic procedures because it may be difficult to distinguish between amelanotic tumours and/or small melanomas. Early diagnosis of a small lesion is mandatory for successful conservative therapy. Radioimmunoscintigraphy (RIS) of malignant melanoma has become an encouraging tool in Nuclear Medicine. 99mTc labelled F (ab')2 fragments of MoAb 225-28S raised against cutaneous melanoma were used. Nine patients were examined: the clinical diagnosis was PUM in 7 cases and choroidal metastases in 2 cases. Due to the size and/or site of the tumor, six eyes were enucleated. In all of these cases histopathology revealed a malignant melanoma. One patient died with disseminated hepatic metastases, 2 months after observation. RIS was positive in 5 of 7 PUM (71.4%) and a false negative result was obtained in 2 patients. Two true negative scintigraphies were observed in the patients with breast carcinomas and choroidal metastases. On the basis of these results, RIS may be valuable to diagnose ocular malignant melanoma, but specificity of MoAb 225-28S needs to be assessed. PMID- 1294596 TI - [Results of trabeculectomy in congenital glaucoma]. AB - Congenital glaucoma has a very serious prognosis. It represents the first cause of blindness in Tunisian children. Trabeculectomy introduced by Cairns in 1968, was initially proposed as second-line treatment in congenital glaucoma surgery. It has now become more frequently used as first-line treatment in this indication. We have already used this technique directly in 35 children suffering from congenital glaucoma with a total of 54 eyes. Forty four eyes underwent a single operation, ten eyes underwent two to four trabeculectomies. Then study of these cases with a mean follow up of 24 months shows an overall success rate of 64% after one trabeculectomy, with or without additional medical treatment. The study of tonometric diagrams shows that the successful results obtained after 3 months persisted in the long term. Trabeculectomy gives better results in congenital glaucoma with intraocular pressure greater than 40 mmHg. Repeated operations are sometimes necessary. In these cases, postoperative subconjunctival 5 fluorouracil (SFU) did not improve the surgical outcome. PMID- 1294597 TI - [The visual field of patients with pseudophakia using kinetic and automated perimetry]. AB - One of the major benefits of pseudophakia is to maintain a good visual field. Visual field was therefore studied in 40 pseudophakic eyes using: 1. kinetic perimetry according to Goldmann using 3 tests: I1, I2, I4; 2. Automated perimetry. Insertion of a posterior chamber intraocular lens was performed in 85% of cases whereas the remaining 15% received an anterior chamber intraocular lens. Visual acuity was > 5/10 P2-P4 in all patients. The results showed a 15% reduction in the visual field compared to normal values. This reduction was concentric and harmonious but was more marked in internal isopters. This reduction was less marked with posterior chamber intraocular lenses. On the other hand, automated perimetry showed that global retinal sensitivity was decreased in pseudophakia, and this deficiency was more pronounced in the periphery. PMID- 1294598 TI - [Prognostic factors of choroidal melanoma: an anatomo-clinical retrospective and statistical study of 76 enucleated cases]. AB - The authors report the results of a retrospective study of 76 patients enucleated for a choroidal melanoma, in whom prognostic factors of survival were studied. The presence of metastasis at the time of diagnosis, the size of the tumor and the epithelioid cellular type are the most pejorative factors (though statistically not significant). A peak mortality can be observed between the second and the fourth year after enucleation. A predominance of the liver metastases is clearly established (75% of the metastases observed in our sample). We observed a majority of small tumors (40%) of spindle cell type (50%). PMID- 1294599 TI - [Unusual uses of liquid perfluorocarbons]. AB - Since the use of low viscosity perfluorocarbon liquids by Chang in 1987, many applications in vitreoretinal surgery have become possible owing to their physical properties (density, viscosity and refraction index). Perfluorocarbon liquids are used exclusively when a vitrectomy is necessary. The main indications are drainage of subretinal fluid by peripheral dehiscence, to facilitate dissection of vitreo retinal proliferation, in retinal detachment by giant tear and in posterior lens dislocation. The authors report three cases illustrating two new indications for perfluorocarbon liquids. Confirming the presence or absence of a peripheral dehiscence in a total retinal detachment if vitrectomy is necessary, subretinal fluid is displaced and escapes via a possible dehiscence. Treatment of vitreretinal incarcerations in a sclerotomic orifice during a vitrectomy is simplified. Easier treatment of this complication is made possible by the injection of perfluorocarbon liquids into the "non-incarcerated" orifice. Despite the more frequent use of perfluorocarbon liquids in vitreoretinal surgery, the possible specific complications which may occur with these products mean that they should be used with caution. PMID- 1294600 TI - [Goldenhar syndrome. Surgical emergency apropos of a case]. AB - We report a case of Goldenhar syndrome in a six week old infant. This patient had bilateral peribulbar choristoma, bilateral pre-auricular appendix and left superior palpebral coloboma with severe exposure keratitis. This condition necessitated an emergency surgical eyelid repair. The authors discuss the different clinical manifestations of this syndrome and therapeutic modalities, particularly the surgical treatment of choristoma and palpebral coloboma. PMID- 1294601 TI - [Eye manifestations and treatment of brain chordoma. Apropos of a case]. AB - We report a case of intracranial chordoma revealed by an isolated abducent nerve palsy in a 4 years old boy. We discuss the possible symptoms of intracranial chordomas and their clinical, radiological and histological diagnosis as well as differential diagnosis. We summarize the available therapeutic modalities and we emphasize the future advantages of proton beam therapy in these lesions. PMID- 1294602 TI - [The Fasanella-Servat technique in the correction of ptosis]. PMID- 1294603 TI - [Bilateral hidrocystoma of the median canthus. Apropos of a case]. AB - Cystic lesions of the eyelids are not uncommon and are variable in nature. A case report of a 42-year-old male patient is detailed. A bilateral cystic lesion was clearly visible at both medial canthuses. Surgical resection was performed under local anesthesia, followed by histopathological study of the specimens. This revealed that these lesions were hidrocystomas, of probable eccrine origin. As many different cystic lesions may be encountered on the eyelids (dermoid cysts, epidermic cysts, cystic basal cell carcinomas...), routine histopathological study of surgically removed cystic specimens is mandatory to obtain an accurate diagnosis. PMID- 1294604 TI - [Treatment of macular hemorrhage]. PMID- 1294605 TI - [Corneal grafts after photorefractive keratectomy using excimer laser]. PMID- 1294606 TI - [Local treatment by epidermal growth factor after epikeratoplasty. A double-blind clinical trial]. AB - Epidermal growth factor is a protein which stimulates epithelial cell growth. We conducted a randomized double blind study between patients treated with PHZ102 (Inpharzam SA, Cadempino, Switzerland) containing EGF, and placebo eyedrops as topical treatment following epikeratoplasty, to evaluate the effect of EGF on corneal reepithelialization. The patients of the EGF group recovered earlier (1 to 4 days) than the patients in the placebo group (3 to 15 days). Therefore, the results obtained confirmed that EGF may reduce the time normally required for complete reepithelialization of the cornea. PMID- 1294607 TI - [Is vitrectomy cataractogenic? Study of changes of the crystalline lens after surgery of retinal detachment]. AB - In order to assess the relationships between vitrectomy and postoperative crystalline lens changes we reviewed the records of 298 selected cases of operated retinal detachments in phakic eyes. We compared two groups: 155 eyes were operated with cryotherapy, vitrectomy and gas injection. 143 eyes received cryotherapy and retro-hyaloid fluid-gas exchange. Follow-up of at least 12 months and detailed description of the lens were available in 90 cases and 82 cases of the two groups respectively. Postoperative lens changes were as follows: nuclear sclerosis occurred in 63% of the vitrectomised eyes, mild in 14%, moderate in 16%, severe in 32%. In contrast, nuclear sclerosis occurred in only 4% of the non vitrectomised eyes, all these cases were noted as moderate. Posterior subcapsular opacities occurred in 4.5% of the vitrectomised eyes versus 2.4% of the non vitrectomised eyes. Nuclear sclerotic changes were correlated with vitrectomy and longer follow-up. Posterior subcapsular cataract was correlated with vitrectomy and larger intraocular gas bubble. PMID- 1294608 TI - [Ultrasonic treatment of hypertonia caused by intraocular silicone oil]. AB - The authors treated 53 patients with uncontrolled glaucoma in silicone oil filled eyes with high intensity focused ultrasound. The silicone oil filled eyes present unusually difficult problems in glaucoma management, since the silicone oil rapidly obstructs filtration openings, and laser techniques have not been effective. The mean pretreatment pressure was 34.2 mmHg. The patients were followed for a mean of 17 months. Seventy-five per cent of ultrasound treated eyes had successful reduction of intraocular pressure to below 20 mmHg with or without concomitant medical treatment at two years after treatment. The complication rate was low in this group of eyes. Five eyes developed hypotonia and three eyes had full thickness scleral perforations but were effectively controlled and developed no other complications during two years of follow-up. This technique appears more effective than cyclo-destructive techniques alone. PMID- 1294609 TI - [Trabeculoretraction by argon laser. 5 and 8-year results]. AB - To appreciate the current place of argon laser trabeculoplasty (ALT) in the therapeutic armamentarium of primary open-angle glaucoma (POAG), the first 211 photocoagulated phakic eyes were analysed. One hundred and fifty-nine eyes had a 5 year-follow-up and 147 eyes had a minimal 8 year-follow-up. These eyes came from an initial group of 151 patients: 76 women and 75 men with a mean age of 66 years. We decided, arbitrarily, to assess trabeculoplasty results according to three combined criteria of failure (insufficient or transient intraocular pressure drop (3 mmHg), progression in visual field loss and need for a filtrating surgery) and to various expected goals: prevent an increase of drugs with their subsequent side effects, taper a non tolerated medical treatment and, lastly, try to cease all medical treatment in non compliant patients. According to these criteria, during the first five years, the cumulative failure rate in the 159 eyes rose steadily from 19% (31 eyes) in the first year to 52% (82 eyes) in the fifth year. The initial mean intraocular pressure (27.22 mmHg) of 7 failures operated on during the first 2 months and that of all 27 operated on failures (24.41 mmHg) was higher than the initial mean intraocular pressure of the 77 successful cases (22.67 mmHg). In the 77 eyes still controlled at 5 years, the intraocular pressure drop was 6.57 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294610 TI - [Prevalence of eye diseases in Basedow disease. Apropos of a prospective study with 85 cases]. AB - The authors report the results of a prospective study, conducted between March 1990 and March 1991, on 85 patients suffering from Graves' disease, who were systematically examined to evaluate the prevalence of ophthalmopathy in Graves' disease. They were graded according to the Nospecs classification: 32 patients had no ophthalmopathy; 21 had only eyelid retraction (grade I in the Nospecs); 32 had a real ophthalmopathy (Grade II) or more in the Nospecs: 27 patients had signs of inflammation (grade II), that were often minor, 14 patients a moderate or intermediate exophtalmos (grade III), 4 patients had corneal injuries (grade V). The authors discuss the problems caused by this classification. PMID- 1294611 TI - [Developmental aspects of diabetic retinopathy during pregnancy]. AB - The course of diabetic retinopathy (DR) was studied in 93 pregnant patients. Results were compared with data from 98 diabetic non pregnant women. Worsening of initial retinal lesions was observed in 16% of the pregnant group whereas only 6% of the control group showed a similar aggravation. The difference between the two groups was statistically significant (p < 0.05). Argon laser panretinal photocoagulation of pre-proliferative and proliferative DR resulted in no subsequent DR-induced complications. On the other hand, the risk of appearance of DR and/or its worsening during pregnancy depends on initial network but mostly on the duration of diabetes mellitus. In conclusion, regular ophthalmologic examination of diabetic patients especially during pregnancy seems crucial for the early screening of any worsening. Furthermore, the importance of pregnancy planning is emphasized. PMID- 1294612 TI - [Multifocal and monofocal implant. Comparative functional results (contrast sensitivity and dynamic visual acuity)]. AB - The functional results (contrast sensitivity and dynamic visual acuity) of 19 multifocal (3 M design) and 14 monofocal intraocular (IOL) were compared. Best corrected visual acuity was > or = 8/10 P 2. Major differences of functional performance in favour of monofocal IOL's were found under standard conditions of vision (low contrast and illumination levels). Dynamic visual acuity allowed accurate evaluation of the difference of performance between these two models of implant. The indications for multifocal IOLs were reconsidered in the light of these results. PMID- 1294613 TI - [Should accommodative strabismus be operated on?]. AB - Hypermetropia is probably not the real cause of accommodative squint. The arguments for this view are the absence of binocular vision in more than half and of the presence of a vertical deviation in about one third of cases of accommodative strabismus. Furthermore, after reduction of this vertical deviation by means of simultaneous surgery upon the horizontal and oblique muscles, binocular vision recovers spontaneously, the accommodative component of the squint disappears and visual acuity improves without glasses. Recent neurophysiologic research explains the beneficial effect of simultaneous surgery. According to these investigations there are two systems of accommodation and convergence; a quick phasic one, where accommodation is linked with convergence and a slow tonic one without interaction. The tonic system is responsible for the neutralization of the excess of convergence induced by hyperaccommodation. Tonic vergence depends on fixation disparity which is eliminated by a vertical deviation and restored by the surgical reduction of this vertical deviation. The fact of wearing positive correction produces and consolidates a hypo accommodation, revealing a latent hypermetropia which could compromise emmetropisation. Furthermore, this correction being associated with squint, is a source of psychological complexes and the cost of an optical treatment is high, considering that spectacles need to be renewed frequently and many times during lifetime. On the other hand, simultaneous surgery removes an important obstacle to fusion and makes the patient independent of spectacles, not only regarding the squint, but also visual acuity. PMID- 1294614 TI - [Anterior lenticonus, suggesting Alport syndrome. Apropos of a first case in Zaire]. AB - Anterior lenticonus is a rare condition, in which there is a conical or spherical protrusion of the anterior surface into the anterior chamber. This is demonstrated by this case report, which has not been previously described in the Black African or Zairian ophthalmological literature. The patient was 28 years old and complained of gradual deterioration of vision over several years. The visual acuity was 20/200. The slit lamp biomicroscope showed an anterior lenticonus with microopacities of the lens. On fundus examination, a fundus albipunctatus-like appearance with midperipheral retinal flecks and macular hole were found. The presence of associated ocular abnormalities, deafness and hematuria, is suggestive of Alport's syndrome. PMID- 1294615 TI - [Idiopathic and secondary chorioretinal folds]. AB - Chorioretinal folds may be observed in many choroidal or retinal diseases. In age related macular degeneration, they are usually associated with retraction of a neovascular membrane and a typically radial pattern of the folds can be seen. In this disease, pigment epithelium folds were recently described. Their clinical and angiographical characteristics are different from chorioretinal folds and the two diseases should not be confused. A 74-old patient presented, in the left eye, with sub foveal new vessels situated at the center of a pigment epithelial detachment (PED). Radial chorioretinal folds surrounded the PED, as frequently observed during follow-up in subretinal neovascular membranes. Nevertheless, right eye fundus examination revealed roughly horizontal, regular and parallel chorioretinal folds. Ultrasonography demonstrated characteristics of idiopathic chorioretinal folds: flattening and thickening of the posterior sclera and choroid. No sign of posterior scleritis was found. These ultrasonographic elements were observed in the left eye away from the central neovascular membrane. The chorioretinal folds therefore seemed to be idiopathic, in a hyperopic patient. The shape of the folds was modified in one eye by a subfoveal neovascular membrane. Chorioretinal folds may occur in different retinal diseases. The associations with many different aetiologies with modification of the shape of the folds, as described in this clinical case, should be emphasized. PMID- 1294616 TI - [Indications of artificial multifocal lenses]. PMID- 1294617 TI - [Surgical excision of encapsulated filtration blebs after trabeculectomy]. PMID- 1294618 TI - Significant anti-HIV activity of new modified polyanionic polymers in vitro. AB - The anti-HIV activities of two new polyanionic polymers (AM 242 and AM 612) were investigated in cell culture-based and biochemical antiviral assays. These compounds inhibited the reverse transcriptases from HIV-1 and HIV-2, using enzyme purified from virions and either a ribosomal RNA or gapped duplex DNA as the template. With the ribosomal RNA template, AM 242 and AM 612 had ID50 values of 1.1 and 0.10 micrograms/ml against the HIV-1 reverse transcriptase. In vitro cell based assays determined that both compounds significantly inhibited both the cytopathic effects associated with HIV-1 infection and the replication of virus in infected cells. AM 242 had an IC50 of approximately 1.0 micrograms/ml, while that of AM 612 was 0.19 micrograms/ml. These two active polyanionic polymers were effective in inhibiting the growth of a panel of HIV-1 isolates and were also active against HIV-2. Although the compounds were toxic at high concentration, they had antiviral activity over a wide range of nontoxic concentrations, yielding a high selectivity index. AM 612 was 100% protective for CEM cells from 320 ng/ml to 1 microgram/ml. Both compounds caused a significant increase in cellular proliferation as determined by the concentration-dependent increase in incorporation of radioactive precursors into cellular macromolecules. PMID- 1294619 TI - Effect of metals on interleukin-6 (IL-6) mitogenic stimulation of murine hybridoma cells. AB - The effect of several divalent metal cations (Co, Cu, Zn, Hg and Pb) on the proliferative response of B9 hybridoma cells to IL-6 has been investigated. At concentrations which are not cytotoxic all the metals inhibited proliferation. The inhibition by Cd and Pb was dependent on both time of addition of the metal and IL-6 concentration. Cd (10 microM) and Pb (50 microM) added at the same time as IL-6 were inhibitory but added 24h later had no effect. Increasing the concentration of IL-6 overcame the inhibitory effect of Cd (10 microM) and Pb (50 microM). Inhibition caused by the other metals was independent of either time of addition or IL-6 concentration. IL-6 did not stimulate an increased intracellular concentration of metallothionein suggesting that the protective effect of IL-6 is not mediated via induction of metallothionein. The results suggest that there are at least two distinct metal sensitive events in B9 proliferation, i) IL-6 reversible inhibition by Cd and Pb ii) IL-6 independent inhibition by Co, Cu and Hg. PMID- 1294620 TI - Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death. AB - Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca(++)ionophore-induced apoptosis. PMID- 1294621 TI - A short incubation with PGE2 affects the proliferative response of T lymphocytes to PWM. AB - In this study we have investigated the role of PGE2 in the activation of human T lymphocytes by PWM. A preincubation of these cells with molar concentrations of the prostaglandin ranging from 10(-9) M to 10(-4) M is able to reduce the expression of IL-2R and CD71 on T lymphocyte membrane during the first days of culture, while the DR molecule which is expressed later in the same experimental conditions is not affected by the treatment of T lymphocytes with PGE2. The PGE2 induced inhibition of IL-2R and CD71 well correlates with the reduction of 3H thymidine incorporation by T cells, indicating that a preincubation of T lymphocytes with PGE2 profoundly affects the proliferative apparatus of these cells when they are stimulated by PWM. PMID- 1294622 TI - Antimicrobial agents induce monocytes to release IL-1 alpha, IL-6, and TNF, and induce lymphocytes to release IL-4 and TNF tau. AB - Evaluation was carried out on the action of different antibiotics on the release of cytokines. Experiments were done in vitro on monocytes and on human lymphocytes. Results show that the majority of the antibiotics tested are able to induce the release of one or more cytokines from their respective producing cells. Among the beta-lactams the most active were the cephalosporins (cephalexin, cefamandol, ceftazidin, and a sulbactam-ampicillin combination) in inducing the release of TNF, IL-1 alpha, and IL-6 from monocytes, and releasing IL-4 and IFN-tau from lymphocytes. The sulbactam-ampicillin combination and cefamandole were extremely active in the production of IFN-tau. Among the lincosamides, clindamycine notably stimulated the release of TNF and IL-6, while lincomycine induced a notable increment of IL-4 from monocytes. Teicoplanin is a very strong inducer of TNF, IL-1 alpha and IL-6. PMID- 1294623 TI - Regulation of murine T-lymphocyte function by spleen cell-derived and exogenous serotonin. AB - The modulatory effects of serotonin on T-cell activity were investigated. T-cell blastogenesis of normal spleen cells was slightly stimulated by the addition of low doses (1 and 10 ng/ml) of the inducer of serotonin release, fenfluramine. In contrast to the stimulatory effects of low doses of fenfluramine, high doses of fenfluramine (1 and 10 ug/ml) or of exogenously added serotonin (> or = 0.1 ug/ml) inhibited T-cell activation. Both the stimulation by low dose fenfluramine and the inhibition by high dose fenfluramine were accentuated by pretreating mice with tryptophan to heighten intracellular stores of serotonin and then inducing serotonin release. Pretreatment of mice with the serotonin inhibitor p chlorophenylalanine (PCPA) abolished the fenfluramine inhibition of T-cell activation indicating that the fenfluramine inhibitory effect was mediated via endogenous spleen cell-derived serotonin. However, the PCPA treatment diminished T-cell activation. These results suggest that endogenous serotonin causes a biphasic dose-response effect on T-cell activity with serotonin being required for optimal T-cell function, low doses being immune stimulatory and higher doses being suppressive. PMID- 1294624 TI - beta-Lactam antibiotic modulation of murine neutrophil cytokinesis. AB - Fourteen cephalosporins, 11 penicillins and 1 monobactam were evaluated for their in vitro modulation of murine neutrophil cytokinesis. As a result, the beta lactam antibiotics were placed into 6 groups based on their effect on random (R) and FMLP-directed (D) migration [Group 1 (no effect): cephalosporin C; Group 2 (R ->D decreases): cloxacillin, cefotaxime, ceftazadime, cefuroxime, cephalothin, cephapirin, cephadine, nafcillin, piperacillin, ticarcillin, ampicillin, oxacillin, aztreonam; Group 3 (R increases D-->): cephaloridine; Group 4 (R increases D increases): cefsulodin; Group 5 (R increases D decreases): cefoperazone, cefoxitin, ceftriaxone, 6-amino-penicillanic acid; Group 6 (R decreases D decreases): cefadroxil, cefazolin, penicillin G, methicillin]. Trypan blue exclusion studies showed that inhibition of R and D by Group 6 beta-lactam antibiotics is not due to overt cytotoxicity. beta-lactam antibiotics inhibiting D also increased neutrophil adherence to plastic at a concentration of 1000 microM. Finally, the [Ca++] inhibitor chlorpromazine significantly abrogates beta lactam- and FMLP-directed migration at a test concentration of 1 microM. PMID- 1294625 TI - Preventive effect of a synthetic immunomodulator, 2-carboxyethylgermanium sesquioxide, on the generation of suppressor macrophages in mice immunized with allogeneic lymphocytes. AB - The effect of 2-carboxyethylgermanium sesquioxide (Ge-132) on the generation of splenic suppressor macrophages (S-M phi) in C3H/He mice (H-2k) immunized with allogeneic spleen cells from C57Bl/6 mice (H-2b) was investigated. We have previously demonstrated that S-M phi expressing I-J antigen, which appeared during alloimmunization, inhibited cytotoxic T lymphocyte (CTL) generation in the MLR and the elimination of these S-M phi before subjection to the MLR resulted in more effective generation of CTL. The CTL activity, which was determined in vivo by the Winn's test, was markedly enhanced when immunized mice received a 100 mg/kg dose of Ge-132. The compound was found to be the most efficacious when injected simultaneously with the immunization. The activity of allospecific CTL co-cultured with M phi fractions obtained from immunized mice in a 4-h 51Cr release assay was shown to be 31% lysis of the target cells as compared with 90% lysis of the target cells in effector cells co-cultured with normal M phi fractions. In contrast, effector cells co-cultured with M phi fractions from Ge 132-treated immunized mice lysed 95% of the target cells. Analysis of the level of I-J antigen expression on macrophages (M phi) obtained from mice 7 days after immunization revealed a > 2.5-fold increase, whereas I-A antigen expression remained constant when compared with splenic M phi from naive mice. In contrast, the opposite effect on I-J and I-A antigen expression was observed in splenic M phi from alloimmunized mice treated with Ge-132. These results suggest that Ge 132 could regulate CTL generation in alloimmunized mice by preventing the generation of I-J+ S-M phi. PMID- 1294626 TI - Antitumor activity evaluation of bromine-substituted analogues of ifosfamide. I. Stereodifferentiation of biological effects and selection of the most potent compounds. AB - The series of 9 compounds, including 3 racemates and 6 enantiomers of bromine substituted analogues of ifosfamide (bromo-, chlorobromo- and dibromofosfamides) have been evaluated for antitumor activity against L1210 leukemia, Lewis lung carcinoma and B16 melanoma in mice. Effective and curative doses of tested compounds were estimated on the basis of computer-assisted elaboration of the dose-effect curves obtained from experimental data. Two oxazaphosphorine drugs, ifosfamide and its congener cyclophosphamide, were used as referentials. Elementary toxicity studies were conducted in parallel in healthy animals and lethal doses were determined. Selection of the most potent compounds was based on the comparison of their therapeutic indices, calculated from the ratio of lethal to effective doses. In effect four compounds which have been shown therapeutically more effective than both referential drugs, were selected for further evaluation in mice bearing advanced tumours. Stereodifferentiation of evaluated biologic effects favouring S(-) isomers was observed in all three groups of compounds. Preliminary observation was also made indicating significant lethality reduction after per os administration of selected agents, which was not paralleled by diminution of their antitumor effectivity. PMID- 1294627 TI - Decreased immunological responses by wortmannin-containing rice culture of Fusarium oxysporum and by purified wortmannin in avian species. AB - Immunological assays were performed in young chicken and duck after they had been fed wortmannin-containing culture of Fusarium oxysporum or purified wortmannin for 2 weeks. The culture significantly decreased humoral response to sheep red blood cell, cell-mediated cutaneous hypersensitivity to phytohemagglutinin and phagocytic activity in isolated peritoneal exudate adherent cells, but only when the concentration was high enough to cause concurrent reduction in body weight gain and hematocrit. Increased dietary metabolizable energy and protein did not affect the toxicity of the culture. On the other hand, purified wortmannin (1 mg/kg diet) significantly inhibited the aforementioned immunological responses prior to the adverse effects on body growth and hematocrit. The data strongly indicate that wortmannin is an immunotoxic substance. The possibility that macrophage is the primary target cell type is discussed. PMID- 1294628 TI - The effects of perfluorodecanoic acid (PFDA) on humoral, cellular, and innate immunity in Fischer 344 rats. AB - The in vivo effects of perfluorodecanoic acid (PFDA) exposure on antibody production, delayed type hypersensitivity (DTH), and natural killer (NK) cell activity were determined. Fischer 344 rats were injected with PFDA (20 mg/kg or 50 mg/kg, 8 days or 30 days prior to sacrifice) and were immunized with keyhole limpet hemocyanin (KLH). Pair-fed and ad libitum-fed control rats were included to evaluate effects of PFDA-induced anorexia. KLH-specific IgG2a production was significantly decreased (p < 0.05) in PFDA-treated rats when compared to ad libitum-fed and pair-fed controls at 8 days but not at 30 days following PFDA treatment. The DTH response of PFDA-treated rats was decreased 8 days and 30 days after PFDA treatment when compared to ad libitum-fed and pair-fed controls, however, the decrease was not statistically significant. NK activity 30 days after PFDA treatment was significantly elevated (p < 0.05) when compared to ad libitum-fed controls, but pair-fed controls had similarly elevated NK activity. NK activity at 8 days after PFDA treatment was not significantly altered. In conclusion, PFDA has been demonstrated to have immunomodulatory effects, some of which may be associated with drug-induced anorexia. PMID- 1294629 TI - The effect of Lasso herbicide on human immune function as measured by in vitro assays. AB - Using in vitro assays, this study was undertaken to determine whether the components of Lasso herbicide formulation had an effect on the human immune system. Mononuclear cells from human peripheral blood were exposed to analytical alachlor, alachlor conjugated to human serum albumin or Lasso formulation over a concentration range from .01 microM-1.0 microM. The effects of the test materials on the following immunological functions were determined: lymphocyte proliferation induced by mitogen or antigen; antibody synthesis of IgG and IgM isotypes in pokeweed stimulated mononuclear cell cultures; cytotoxic T cell proliferation; lysis of target cells by natural killer cells and lymphokine activated killer cells. The data demonstrated that the test compounds had no significant, dose related effect on the function of immunocompetent cells. Hence, the data suggest that the components of the Lasso formulation have no effect on the human immune system. PMID- 1294630 TI - Crohn's disease and the Jews. AB - Several epidemiologic studies of Crohn's Disease (CD) from the northern hemisphere show high rates of the disease among Jews. Israel has absorbed many Jews from those countries and the rates of CD in Israel are lower than in their place of birth. Important, too, among immigrants from the middle east Mediterranean countries, the rates appear to be higher than those in their countries of origin, where the disease is rare. CD has a genetic predisposition, but we physicians cannot ignore the environmental factors. PMID- 1294631 TI - Diversion colitis--20 years a-growing. AB - During the last decade, clinical and pathologic studies of diversion colitis have led to a better understanding of its nature. The clinical features are well described, and the endoscopic appearances, and gross and microscopic pathology are now defined. Thus, firm diagnosis and distinction from other colitides, notably ulcerative colitis and Crohn's disease, are possible in most cases. Restoration of the fecal stream cures diversion colitis, which in some cases may be successfully treated with short-chain fatty acid enemas, although the efficacy of this method remains to be substantiated. An understanding of the pathogenesis of diversion colitis (currently unknown) may lead to better methods of prevention and treatment. PMID- 1294632 TI - Chronic idiopathic esophageal ulceration in the acquired immunodeficiency syndrome. Characterization and treatment with corticosteroids. AB - Study objectives were to characterize the clinical syndrome of chronic idiopathic esophageal ulceration in patients with acquired immunodeficiency syndrome (AIDS), to determine the extent of local human immunodeficiency virus (HIV) infection, and to evaluate the effect of corticosteroid therapy upon symptoms and healing. Twelve AIDS patients with chronic esophageal ulcers whose etiology remained unknown after clinical evaluation were the subjects. All patients complained of severe odynophagia, chest pain, and weight loss. Barium radiography and endoscopy demonstrated large, undermined ulcers with severe acute inflammation. No evidence of herpes simplex viruses I or II, cytomegalovirus, fungi, or tumors were found histologically. Evidence of HIV was found in all ulcers using a combination of RNA in situ hybridization, immunohistochemistry, and quantitative antigen capture enzyme-linked immunosorbent assay of tissue homogenates. Steroid therapy by the oral or intravenous routes or by direct intralesional injection resulted in pain relief, weight gain in 10 patients, and ulcer healing in five patients. A characteristic clinical syndrome of chronic idiopathic esophageal ulceration may occur in patients with AIDS, related to local HIV infection in the esophagus. Corticosteroids relieve symptoms and may promote healing of the ulcer. PMID- 1294633 TI - Healing and relapse of duodenal ulcer during ranitidine therapy in the elderly. The RUDER Study Group. AB - A total of 2,109 outpatients with active duodenal ulcer (DU) entered an open, prospective study in order to investigate factors influencing healing and relapse during 2 years of ranitidine therapy (300 mg daily for healing, 150 mg as maintenance treatment). In a retrospective analysis, we evaluated the influence of age. Symptoms related to DU in 1,899 evaluable cases in patients over 65 years of age (n = 185) were identical to those of DU patients younger than 65 years old (n = 1,714). Rapid healing within 2 weeks of ranitidine therapy was less frequent in the elderly (32.5%) than in younger patients (40.7%) though identical healing rates (94.1%) in each group were achieved by continuation of ranitidine therapy for 8 weeks. Cumulative recurrence rates during the 2 years of long-term therapy were lower (17.3%) in old age than in patients under 65 years of age (23.3%). Adverse events were rare in both age groups. We conclude that DU healing during ranitidine is delayed in old age. Additional differences in relapse rates in favor of the elderly suggest that DU disease has a different course in the elderly. PMID- 1294634 TI - Low prevalence of gastric metaplasia in the duodenal mucosa in Peru. AB - We compared the prevalence of gastric metaplasia of the duodenal mucosa (GM) and its characteristics in 204 Peruvian patients from a low socioeconomic level with the corresponding prevalence reported in dyspeptic patients from a developed country, the United Kingdom. Gastric metaplasia was significantly less prevalent in the Peruvian than in the United Kingdom series. However, when present, GM was not significantly different in extent or frequency of colonization by Helicobacter pylori or association with active duodenitis, despite a higher prevalence of H. pylori-associated gastritis. Hypochlorhydria was markedly more frequent in the Peruvian than in the United Kingdom series. The finding of a low prevalence of H. pylori-colonized GM in patients with previously reported low prevalence of duodenal ulcer gives further support to a pathogenic link between both conditions. PMID- 1294635 TI - Early gastric cancer in southern Taiwan. AB - Between January 1986 and November 1990, 231 patients underwent resection for primary gastric adenocarcinoma at Chang Gung Memorial Hospital in southern Taiwan. Thirty-nine (17%) of these patients had early gastric cancer (limited to the mucosa or submucosa regardless of nodal metastases). Epigastric pain was the most frequent symptom (71.8%). The lesions were located in the lower third of the stomach in 84.6% of the patients and in the middle third in 15.4%. A preoperative diagnosis of gastric cancer was achieved in 94% of patients by endoscopic examination with biopsies. All of the patients underwent distal subtotal gastrectomy without mortality. Macroscopically, 84.6% of cases were included in types IIc, III, and IIc-III. One patient died of multiple liver metastases 3.2 years after operation. The cumulative survival rate at 5 years is 92.9%. We comment on these matters and place early gastric cancer in Taiwan into a more global context. PMID- 1294636 TI - Preoperative clues to Crohn's disease in suspected, acute appendicitis. Report of 12 cases and review of the literature. AB - Twelve patients who underwent laparotomy for suspected acute appendicitis were found to have Crohn's disease of the terminal ileum. Appendectomy was performed in all although in only four patients was the appendix grossly inflamed. Postoperative complications, either abscess or fistula, developed in four patients (33%). Careful investigation of the records revealed some preoperative diagnostic clues: a history of recurrent abdominal pain and/or diarrhea (83%), physical examination revealing normal temperature (50%), and laboratory results compatible with a chronic process such as microcytic anemia (33%) and hypoproteinemia/hypoalbuminemia/hypocholesterolemia (50%). As the differential diagnosis between Crohn's disease and appendicitis is difficult and the surgical approach to the appendix in the presence of Crohn's disease is controversial, we illuminate some practical points in the preoperative evaluation of these patients and deal with the question of whether appendectomy should be performed in these patients. PMID- 1294637 TI - Ki-67 antibody labeling index in colorectal carcinoma. AB - Ki-67 labeling index of 58 colorectal carcinomas and 10 normal colonic mucosa samples was determined by the use of an immunohistochemical staining technique. The Ki-67 labeling index in colorectal carcinomas ranged from 15.7 to 63.6% (mean +/- SD of 38.5 +/- 10.5) and was significantly higher than the index for normal colon mucosa (mean +/- SD of 14.1 +/- 2.8). The mean Ki-67 labeling index was significantly higher in Dukes' B and Dukes' C tumors than in Dukes' A tumors, but the index did not correlate with the size of the tumor. There was no correlation between the Ki-67 labeling index of the tumor and lymph node involvement. The present study disclosed that the Ki-67 labeling index correlated with local invasion of colorectal carcinoma, but not with metastasis of the tumor. PMID- 1294638 TI - The effect of loperamide on anorectal function in normal healthy men. AB - Loperamide improves anorectal functioning in patients with diarrhea and incontinence. Loperamide reduces sensitivity of the recto-anal inhibitory reflex and increases internal anal sphincter tone. Additionally, it has an effect on rectal compliance in incontinent patients with diarrhea. We studied the effect of loperamide versus placebo at different distances from the anal verge in 18 healthy male volunteers, using standard anorectal manometry was a double-blind, two-factorial design. We found that the recto-anal inhibitory reflex is most pronounced when stimulated in regions close to the anal canal and that distention stimuli are also perceived best in that region. Both effects are counteracted by loperamide. We found no effect on internal sphincter tone or rectal compliance. These results imply a gradient of sensitivity for rectal perception and the recto anal inhibitory reflex in healthy volunteers. Loperamide action on both mechanisms suggests a common mediator for both effects. PMID- 1294639 TI - Diagnosis of the acute abdomen in the neurologically stable spinal cord-injured patient. A case study. AB - The diagnosis of the acute abdomen in the spinal cord injured patient is difficult. Diagnoses are often so delayed that approximately 10% of these patients die of acute abdominal problems. The presentation also varies with the level and duration of injury. An understanding of the functional neuroanatomy of the abdominal wall and viscera aids in timely diagnosis. I present an illustrative case and describe the pertinent functional neuroanatomy. PMID- 1294640 TI - Injection sclerotherapy as a cause of Klebsiella pneumoniae peritonitis. AB - We report a case of Klebsiella pneumoniae peritonitis after endoscopic sclerotherapy and discuss its pathogenesis and risk factors. We also review previous cases in the literature and make recommendations for prophylactic therapy. Endoscopists should be aware of peritonitis as a possible complication of endoscopic sclerotherapy. PMID- 1294641 TI - A cecal diaphragm associated with the use of nonsteroidal anti-inflammatory drugs. AB - In the small intestine, strictures and diaphragms causing obstructive symptoms are well known to occur in patients using nonsteroidal anti-inflammatory drugs. Recently, two cases of nonsteroidal anti-inflammatory drug (NSAID)-associated diaphragm-like colonic stricture were reported as unexpected findings in patients being investigated for iron-deficiency anemia. We present a third such case that occurred in the cecum in a 49-year-old woman with rheumatoid arthritis who had been taking NSAIDs for 5 years. PMID- 1294642 TI - Pancreatitis in ulcerative colitis. AB - A 19-year-old man without apparent predisposing factors was found to have chronic pancreatitis and 6 months later developed ulcerative colitis. Is there a real association between pancreatitis and inflammatory bowel disease? We discuss previous reports. PMID- 1294643 TI - Endoscopic diagnosis and treatment of Mirizzi's syndrome. AB - Mirizzi's syndrome is the name given to common bile duct obstruction secondary to a stone in the cystic duct. The cause of the biliary obstruction is often difficult to establish before operation. We report two cases of Mirizzi's syndrome, diagnosed endoscopically and treated without surgery. One of the patients was treated by drainage of both the common bile duct and the gallbladder associated with monooctanoin dissolution of the gallstone. The other was treated by common bile duct stenting. PMID- 1294644 TI - Colonoscopy: a prospective report of complications. AB - Patients (N = 2,097) undergoing ambulatory office colonoscopy were followed to determine the incidence of endoscopic complications. In this group, 1,320 patients had diagnostic colonoscopy with or without biopsy; 777 patients had 2,019 polyps removed. Three of 2,097 patients (0.1%) had transient hypotension requiring i.v. fluid resuscitation and oxygen administration. All patients went home without sequelae. Acute postpolypectomy bleeding occurred in 11 of 777 patients (1%) requiring acute management; bleeding was controlled during colonoscopy in all. Postpolypectomy syndrome occurred in 9 of 777 patients (1%). All patients were treated medically. Late postpolypectomy bleeding occurred in 15 of 777 patients (2%). Perforation occurred in two of 777 patients (0.3%), at 1 and 9 days postpolypectomy. Both patients underwent surgery with uneventful recoveries. We conclude that office colonoscopy including polypectomy is safe. The overall complication rate for therapeutic ambulatory colonoscopy was 5%, with major events requiring hospitalization in 2% of patients. PMID- 1294645 TI - Gut transit in coproporphyria? PMID- 1294646 TI - Giant inflammatory fibroid polyp mimicking gastric cancer. PMID- 1294647 TI - Attempt to reverse atrophic gastritis associated with common variable immunodeficiency. PMID- 1294648 TI - Does vasculitis occur in abdominal tuberculosis? PMID- 1294649 TI - [Characteristics of group A streptococci isolated from children with non suppurative complication or severe infection]. AB - We determined the characteristics of group A streptococci isolated from 29 sporadic cases with non-suppurative complication or severe infection during a 15 year period from 1977 to 1991. The clinical diagnoses of children included 4 patients with rheumatic fever, 2 with reactive arthritis, 2 with central nervous system complication, 5 with glomerulonephritis, 11 with Honoch-Scholein purpura, 4 with sepsis and 1 with empyema. Twenty-four strains were isolated from throat swabs, 4 from blood specimens and one from pleural fluid. M/T-serotypes and the number of isolates were as follows; 1/1:10, 3/3:1, 3.3R/3:3, 4/4:7, 5/NT:1, 12/12:3, 18/18:2, 62/12:1, NT/13:1. All 29 isolates had productivity for at least one of streptococcal pyrogenic exotoxins (SPEs) A, B and C. Two strains were positive for A, 2 for A and B, 3 for A, B and C, 9 for B and 13 for B and C. Of 11 isolates from patients with Henoch-Schonlein purpura, 7 and 2 strains were serotyped in M1 and M4, respectively, but none was in M12. Ten of 11 isolates were positive for SPE B or SPEs B and C. PMID- 1294651 TI - [Culture-positive Legionella pneumonia in Japan, 1980-1990. Working Party for Legionellosis, Japanese Ministry of Health and Welfare]. AB - The Working Party for Legionellosis headed by the Japanese Ministry of Health and Welfare processed to standardize the diagnostic procedures for Legionella pneumonia, as the first step to clarify the actual occurrence of patients with this respiratory disease. All the clinical data were collected and analysed on the 28 culture-confirmed patients in Japan during the past 11 years, from 1980 through 1990. The 28 patients were distributed throughout Japan, from Hokkaido to Kyushu. Out of 28 patients, 18 were community-acquired and 10 were nosocomially infected. In 8 of 18 community-acquired patients, any significant underlying disease was not observed. Though it was dominant in the age group in their 60s & 70s, victims were distributed in adults over 20 years of age and even in a new born baby. Only 5 out of 28 patients recovered successfully. From the autopsy findings, in 5 out of the remaining 23 expired patients, Legionella pneumonia seemed to be successfully treated, but other disease or other bacterial pneumonia put an end to the patients. The results of clinical laboratory tests and the efficacy of antibiotics to Legionella pneumonia were essentially the same as those reported in the literature. PMID- 1294650 TI - [Identification of strains on recurrent Haemophilus influenzae infections in patients with chronic respiratory tract infections]. AB - Nontypable Haemophilus influenzae is one of the most important pathogenic bacteria in respiratory tract infections. H. influenzae is most frequently associated with recurrent infections in chronic respiratory tract infections (CRTIs). It is known that H. influenzae often reemerges after the antibiotic treatment has been stopped. We analyzed serotype, biotype, and the OMP patterns of H. influenzae isolates from sputum of CRTIs patients to determine whether an exacerbation is caused by an identical H. influenzae strain, or by a new H. influenzae strain. One hundred eighty nine strains of H. influenzae were obtained from 124 exacerbation from 24 patients. The first and second isolates were identical in 23 out of 33 exacerbations (< or = 15-days interval between each exacerbation) and also in 22 out of 34 exacerbations (15 < days but < or = 30 days interval between each exacerbation). This is called early recurrence. In contrast, the first and second isolates were different in 28 out of 34 exacerbations (> 30-days interval between each exacerbation). This is called late recurrence. These results suggest that early recurrence and late recurrence of recurrent H. influenzae infections occur in a different mechanism. PMID- 1294652 TI - [Typing system for Clostridium difficile by western blotting using antisera against ten different serogroup strains]. AB - Western blotting using antisera against each of reference ten serogroups was evaluated as a typing system for Clostridium difficile. A total of 164 isolates of C. difficile (114 epidemiologically unrelated and 50 isolates from a hospital outbreak in New York) were tested. Blotting patterns for the ten reference strains showed serogroup-specific bands located in the 30-60 kDa when each homologous antiserum was used. At greater than 60 kDa, variations in each serogroups were observed; these variations were used for subserogrouping the isolates. Serogroup A, G, H, and K were most frequently recovered in the group of epidemiologically unrelated isolates. Subserogroup G-1 strains of serogroup G was isolated from 28 of 36 patients (78%) of the hospital outbreak. The result suggested that the subserogroup G-1 strain was the major cause of infection in the hospital outbreak. A total of 46 of the 114 unrelated isolates (40.4%) and 9 of 50 outbreak isolates (18%) did not react with any of reference antisera and classified as nontypable. The western blotting was found to be useful not only as an epidemiological tool but as a typing system for C. difficile. PMID- 1294653 TI - [Relationship between hand-washing activity of disinfectants and in vitro bactericidal activity in the presence of peptone]. AB - A study was made on the relation between in vitro bactericidal activity against Staphylococcus epidermidis which is the main bacterial flora of skin and the disinfecting activity of hand-washing with povidone-iodine, sodium hydrochloride, chloramin-T, chlorhexidine gluconate and benzalkonium-chloride. Although the bactericidal activity of povidone-iodine and sodium hydrochloride was significantly high as compared with those of the other three disinfectants, both povidone-iodine and sodium hydrochloride showed no or a little hand-washing effects. In vitro the bactericidal activity of both povidone-iodine and sodium chloride were significantly retarded by the addition of peptone in the reaction mixture. On the other hand, chloramin-T, chlorhexidine gluconate and benzalkonium chloride showed a high disinfecting activity in hand washing in spite of low in vitro bactericidal activity. Moreover, the bactericidal activity of these three disinfectants were not suppressed by the addition of peptone in the reaction mixture. These results strongly suggested that hand washing effect of disinfectant is affected by the protein on the hand and that hand-washing activity of disinfectant should be determined by in vitro bactericidal activity in the presence of peptone. PMID- 1294654 TI - [Enteroadherent Escherichia coli exhibiting localized pattern of adherence among infants with diarrhoea in Brazil--incidence and prevalence of serotypes]. AB - The incidence of enteroadherent Escheridhia coli exhibiting localized adherence to HeLa cells was investigated using the EAF probe (Nataro et al., J. Infect. Dis., 152:560-563, 1985) among 126 infants below 3 years of age along with 126 age-matched healthy controls in Brazil. The EAF probe proved to be sensitive and specific in detection of enteroadherent E. coli. EAF-probe positive E. coli was isolated from 23.0% of the infants with acute diarrhoea while the corresponding rate of isolation from healthy controls was 11.9%. EAF-probe positive E. coli strains belonging to the classical enteropathogenic E. coli (EPEC) serogroups were more often associated with diarrheal cases (18.3%) than with strains isolated from control healthy infants (5.6%). The predominant EAF-probe positive E. coli serotypes were O55:H-, O111:H2 and O119:H6. These serotypes, especially O111:H2, were mainly isolated from cases with diarrhoea suggesting a strong causal association. Among the EAF positive non-EPEC serotypes, the most prevalent serotype was O88:H25 and this represents a, hitherto, unrecognized diarrheagenic E. coli serotype. PMID- 1294655 TI - [Epidemiological study of Staphylococcus aureus isolated from the Japanese National University and Medical College Hospitals with coagulase typing, and production of enterotoxins and toxic shock syndrome toxin-1]. AB - Coagulase typing, staphylococcus enterotoxins (SE) A to E or toxic shock syndrome toxin-1 (TSST = 1) production, and susceptibility to Oxacillin (MPIPC) were examined in 430 strains of S. aureus, which were isolated from clinical specimen of 43 Japanese National University or Medical College Hospitals during the one month period of August in 1990. Methicillin-resistant Staphylococcus aureus (MRSA): more than 4 mmg/ml of minimum inhibitory concentration for MPIPC in Mueller-Hinton broth containing 2% NaCl, occupied 58.6% of all the S. aureus, and more than 60% of the strains from admitted patients in all the areas of Japan except Hokkaidoh. Coagulase type II, SEC and TSST-1 producing strains were most frequently detected, 34.5% of all the MRSA. This kind of strain was distributed mainly in the eastern part of the Honshyu island, and showed high percentage especially in the Tohhoku and the Chyubu area. The second most frequent kind of MRSA was coagulase type II, no SE nor TSST-1 producing one, 15.4%, which was distributed mainly in the western part of Japan. Coagulase type IV, SEA producing MRSA strains and Coagulase type II, SEA, SEC and TSST-1 producing strains were detected in relatively high incidence, 10.3% and 8.7% respectively. Coagulase type III, no SE nor TSST-1 producing MRSAs demonstrated characteristic distribution, and were detected only in the western part of Japan, presenting the highest incidence in the Shikoku Island. PMID- 1294656 TI - [Detection of mycobacteria by DNA amplification]. AB - Polymerase Chain Reaction (PCR) was used to detect and to identify Mycobacterium species. In this study, 13 out of 14 Mycobacterium species were detected by using six pairs of oligonucleotide primers. The PCR product was detected by non isotopic southern blot hybridization even when as little as 10 fg of purified M. tuberculosis DNA was used. And 8 mycobacterial species were identified by PCR Restriction Fragment Length Polymorphism (RFLP) using two kinds of endonuclease. PMID- 1294657 TI - [Mycoplasma pneumoniae respiratory tract infection prevailing among infants at a nursery school]. AB - Mycoplasma pneumoniae (M. pneumoniae) infection in infants had been considered to be very rare, but recently some clinical cases have been reported. We experienced an epidemic of M. pneumoniae infection in a nursery school, and compared M. pneumoniae infection in infants with that in preschool and school children to investigate the features of infantile M. pneumoniae infection. We obtained the following clinical findings in 15 infantile patients with M. pneumoniae infection: The maximum body temperature scarcely increased to 38.5 degrees C or more and the period of high temperature and cough was shorter in infant patients than in preschool and school aged patients. Stridor occurred in 4 patients but skin disorder was not observed. In the laboratory findings, the white blood cell count tended to increase with no changes in neutrophil/lymphocyte ratio and CRP increased slightly. M. pneumoniae antibody was negative in all the patients except 3 and old hemagglutination tests were positive in only 4 patients. The chest X-ray examinations showed a mild increase in the hilar shadow. However, the sequentially located homogeneous shadow which is commonly seen in preschool and school aged patients was not detected. M. pneumoniae antibody scarcely increased in infantile patients but M. pneumoniae was isolated by throat culture from 14 of the 15 patients who were diagnosed as having M. pneumoniae infection. PMID- 1294658 TI - [Changes in serotypes of clinical isolates of Pseudomonas aeruginosa by anti pseudomonal drugs]. AB - Forty-two isolates of P. aeruginosa from various infections were each incubated in Mueller-Hinton broth including piperacillin, cefsulodin, ceftazidime, imipenem, gentamicin or norfloxacin (1MIC-4MIC) at 35 degrees C for 18 hours, and serotyped using monoclonal antibodies. Serotypes of 4 (9.5%)-8 (19.0%) of the 42 isolates each changed to different groups after incubation. No relationship was found between serotypes of the formed variants and anti-pseudomonal drugs used. When P. aeruginosa TA-2 was exposed to cefsulodin at different concentrations (1MIC and 2MIC) under the above conditions, the distinct variants different in serotypes were formed according to the drug concentrations. Furthermore, P. aeruginosa TA-2 and TA-13 were incubated in Mueller-Hinton broth including cefsulodin (1/2 or 2MIC) and gentamicin (1/2MIC), respectively, and the growth curves of parent and variant cells were determined. In the experiments, the variants appeared 6 hours after onset of the incubation and grew with the parents. The present results may explain our findings previously reported; coexistence of colonies different in serotype of P. aeruginosa isolated from some individual patients. The results indicate the possibility that alteration in bacterial surfaces in association with changes in serotypes might occur in vivo in these patients infected with P. aeruginosa and treated with anti-pseudomonal drugs. PMID- 1294659 TI - [Analysis of chest radiographs of culture positive Legionella pneumonia in Japan, 1980-1990. Working Party for Legionellosis, Japanese Ministry of Health and Welfare]. AB - We analyzed the initial and follow-up chest radiographs of 28 patients with culture-positive Legionella pneumonia, and developed a scoring system to quantitate the severity of radiological findings for pneumonia. Intrapulmonary shadows were observed on the initial chest radiograph in 26 patients, but pleural effusion was noted in only one. In one patient the initial chest radiograph had probably been obtained too early to reveal any pulmonary change. Alveolar shadows were noted on the initial radiograph in 21 (81%) patients, and interstitial shadows in 5 (19%). In ten (38%) patients shadows were present in both lung fields. Shadows were prominent in the middle and lower lung fields. A cavity was noted in only one patient, and pleural effusion was also noted at some time during the clinical course in 19 (70%). A large amount of pleural effusion was observed in four patients. The average pneumonia severity score was 3.3 in the 9 patients who survived, and 5.1 in the 17 who died (p > 0.05). The mortality rate was 53% in the 17 patients with pneumonia severity score of 5 or less and 89% in the 9 patients with a score of 6 or more (p > 0.05). Twelve patients died within one week after the initial chest radiograph was obtained. There were no differences among patients with community-acquired infection with or without underlying disease and those with nosocomial infection in characteristic and extension of shadow, presence of pleural effusion, or pneumonia score. The chest radiograph of Legionella pneumonia include bilateral shadow findings characteristic, pleural effusion and rapid progression of shadow, and are clinically useful for diagnosis. PMID- 1294660 TI - [A case of perinatal transmission of human immunodeficiency virus--diagnosis of HIV infection by culture and PCR]. AB - A child born from a mother with HIV infection was reported. We have followed the patient from 3 month old of age. Her HIV antibody disappeared at 7 month by EIA, and at 10 month by WR. But we confirmed her HIV infection by PCR and HIV culture, repeatedly at those times, PCR and HIV culture are thought to be necessary for sero-negative infants born from mothers positive for HIV antibody. PMID- 1294661 TI - [A case of chronic myelogenous leukemia with pulmonary aspergillosis diagnosed by the detection of circulating Aspergillus antigen]. AB - Immunocompromised hosts usually develop invasive mycotic disease. Among many pathogenic fungi. Aspergillus spp, is the most common pathogen of respiratory infection. Early diagnosis of invasive type pulmonary aspergillosis is still difficult, and the treatment is usually difficult. Many investigations have recently suggested that detection of Aspergillus antigen from sera of the patients is useful for early diagnosis to save their lives. We have experienced a case diagnosed by the detection of circulating Aspergillus antigen by Pastorex Aspergillus, who was a 64-year-old female with the blastic crisis chronic myelogenous leukemia. After anti-leukemic chemotherapy, she suffered from pneumoniae with pleural effusions and severe hypoxia, which did not respond to antibiotics. At this point, her serum sample showed positive Aspergillus antigen by Pastorex Aspergillus. She was treated by intensive antifungal chemotherapy, and thereafter improved quickly. Titers of Pastorex Aspergillus were well correlated with her clinical course. The sensitivity of the test requires further improvement, but the specificity of the test is considered to be high enough for clinical use. PMID- 1294662 TI - [Clinical significance of anti-Helicobacter pylori antibody in the diagnosis of Helicobacter pylori infection in chronic gastritis]. PMID- 1294663 TI - [Studies on risk factors influencing delayed resolution of pneumonia]. AB - Among 61 patients admitted to our hospital because of bacterial pneumonia during the last six years, we investigated several risk factors influencing delayed resolution of pneumonia shadows, such as age, extent of the lesion, period of fever and sputum production after antibiotic therapy, WBC, CRP and PaO2 values on admission, the period of increased values of WBC and CRP, the presence or absence of etiological pathogens, the period from the appearance of symptoms to admission, and the period of drug therapy. In our series, the period from appearance of symptoms to admission (r = 0.62) and that of increased WBC (r = 0.35) significantly correlated with the period of pneumonia shadows to the time of their resolution. Similar results were obtained from the multiple variate analysis of various factors. These results suggest that the duration period (nontherapy period) of inflammation closely associated with leukocytosis plays a crucial role in the delayed resolution of pneumonia shadows. PMID- 1294664 TI - [Kinetics of the complement subcomponent C1q production of peritoneal macrophages in NZB/W F1 female mice]. AB - To clarify the role of local production (exohepatic) of complement on primary host defense mechanisms against microbial infections in the host who decreased the amount of complement in serum, the kinetics of the complement production by the complement-producing cells in exohepatic tissue was examined by measuring the amount of C1q, subcomponent of the first complement component, in cultured supernatant of the monolayer of peritoneal macrophages (PM phi) collected from 5, 15, 35, and 48 weeks-old female mice of NZB/W F1 (B/W F1). The C1q production of PM phi in B/W F1 mice showed remarkable decrease at 15 weeks-old. After that, however, the C1q producibility of PM phi recovered gradually and, at mice 48 weeks old, the complement produced finally exceeded the amount observed in mice 5 weeks-old, contrariwise the C1q values in serum were significantly lowering in the same aged mice. The increased production of C1q of PM phi was observed in both 35 and 48 weeks-old mice, of which the value corresponded with increase of anti-nuclear antibody titer in serum and of the amount of protein in urine. On female mice of ddY (control), the amount of C1q production of PM phi in 5 weeks old mice was two-fold higher than that of 5 weeks-old B/WF1 mice. But at 15 weeks, the production showed a 1/2 decrease in that of mice 5 weeks-old and the decreased values were kept to 35 weeks-old.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294665 TI - [Analysis of urinary tract infections in hospitalized elderly patients, with particular reference to the use of diapers]. AB - We investigated the clinical and laboratory data of 215 hospitalized patients (mean age were 76.9 +/- 12.1) to analyze both the characteristics of senile UTI and the influence of the way of urination. UTI was present in 121 of 1897 patients (6.4%), 95 of whom (78.5%) were female. Comparison of the parameters between non-infected and infected patients were as follows: body temperature was 36.57 +/- 0.64 degrees C vs. 37.49 +/- 0.77 degree C; WBC, 5410 +/- 2040/microliters vs. 7260 +/- 3230/microliters; CRP, 1.2 +/- 2.4 mg/dl vs. 3.5 +/ 3.4 mg/dl; mean class of urinary RBC, 0-1/hpf vs. 3-5/hpf; and mean class of urinary WBC, 5-10/hpf vs. 30-50/hpf. All parameters were significantly elevated (p < 0.001) in the patients with UTI. The rate of detection of causative bacteria was 88.7%; with 14.8% Escherichia coli, 12.8% Providencia species, 9.6% Enterococci, and 8.7% Pseudomonas aeruginosa. Patients with UTI were divided into three groups according to their method of urination: normal urination, use of diapers and catheterization. Body temperature (> or = 37.5 degrees C) was 2.8%, 10.1% and 34.9%; WBC (> or = 9.000), 2.7%, 6.1%, and 14.3%; CRP, 16.9%, 36.1% and 51.1%; urine RBC (> or = 6-10/hpf), 8.4%, 7.1% and 36.1%; urine WBC (> or = 15 30/hpf), 20.4%, 44.4% and 76.9%, respectively. There was a significant difference (p < 0.05-0.001) between all parameters except for urine RBC between the normal urination patients and diaper using patients. This investigation suggested that the use of diapers was a risk factor for UTI in elderly patients. PMID- 1294666 TI - [Detection of Ureaplasma urealyticum by polymerase chain reaction]. AB - A polymerase chain reaction (PCR) procedure for detection of Ureaplasma urealyticum was developed. A set of oligonucreotides based on sequences within the 16S ribosomal RNA gene from U. urealyticum were used as extension primers for the PCR. A DNA fragment of 397 bp was amplified by the PCR, when U. urealyticum DNA was template for the PCR. No amplified product was detected from other bacterial DNA including those of Mycoplasma genus. The amplified DNA fragment of 397 bp was detected on agarose gel electrophoresis, when DNA of > or = 10(2) cells of U. urealyticum per PCR was used as template for the PCR. Thus, the PCR procedure was shown to be a simple, rapid and specific method for detection of U. urealyticum and could be applied to detection of U. urealyticum from clinical specimens. PMID- 1294667 TI - [Shigella flexneri strains having a new type antigen 89-141]. AB - Two Shigella strains (89-141 and 89-11) isolated from the stool of patients returning from abroad (both from India) in Tokyo in 1989 showed an atypical serologic reaction of agglutination with only polyvalent antiserum to S. flexneri prepared commercially. These strains had the typical biochemical characteristics of S. flexneri and were biochemically identical. Both strains were positive for Sereny test in guinea pig eye and cell-invasion test in HeLa cells. The strains also had virulence-plasmid encoding outer membrane proteins, indicating pathogenicity. The results of antigenic analyses showed that the strains were serologically identical to each other and gave significant cross-reactions with S. flexneri variant Y that has only group 3, 4 factor antigen. However, the results of reciprocal absorption tests showed that the O antigen of these strains was not identical to S. flexneri variant Y, and they were confirmed to have an additional type-specific antigen which is not included among the known S. flexneri type antigen I-VI or provisional type 88-893 which were proposed by us in 1992. Furthermore, one stock strain (TSH508) formally identified as S. flexneri variant X has this type antigen, suggesting that the new antigen can be classified into two subtypes by combination of group factor antigen. Strain 89 141 is designated as the test strain for this new type antigen of S. flexneri. PMID- 1294668 TI - [Significance of normal oral flora, particularly group oral streptococci as defense mechanism against infection in healthy individuals (normal defense mechanism by oral Streptococcus group)]. AB - The alpha-streptococci, consisted of normal oral flora mainly, with inhibitory activity against pathogenic microbes in healthy individuals was investigated by group A Streptococcus (indicator strain 6-22 nonmucoid T-12). Rate of alpha streptococci with inhibitory activity against group A Streptococcus was increased as aging, and the rate in pre-school children was higher than that in school children. These results suggested that more than 90% of the tested alpha streptococci with strong inhibitory activities (S. salivarius) against indicator strain had inhibitory activities against group A Streptococcus (mucoid T-6), H. influenzae, S. pneumoniae, group C Streptococcus, and from 40% to 70% of the tested strains had also inhibitory activities against other pathogens. As there were many strains of alpha-streptococci with inhibitory activities against pathogens, that usually detected in the upper respiratory infection, the problem on the strains in the future will explain significance of the defense mechanism against upper respiratory infection and this can be applied clinically. PMID- 1294669 TI - [Distribution of Clostridium botulinum and Clostridium tetani in Okinawa Prefecture]. AB - Soil samples from the sugar cane fields and muscovado samples from the manufacturing processes at sugar manufacturies in many parts of Okinawa Prefecture were collected, mainly in 1988 and 1989, and examined for Clostridium botulinum and Clostridium tetani. Of 290 soil samples 21 (7.2%) were positive for C. botulinum. Four (1.4%) and 17 (5.9%) contained types E and C respectively. C. botulinum type E was demonstrated in the North and South areas of Okinawa main island. Type A and B were not demonstrated from soil samples in Okinawa Prefecture. Of 53 samples of the manufacturing processes of muscovado 5 (9.4%) were positive for C. botulinum type C. Type A, B and E were not found from muscovado samples in Okinawa Prefecture. Of 290 soil samples 54 (18.6%) were positive for C. tetani. Among the 53 muscovado samples from the manufacturing processes of the sugar cane, 10 (18.9%) were positive for C. tetani. PMID- 1294670 TI - [The first cholera case diagnosed early in the clinical laboratory by DNA probe method]. AB - An alkaline-phosphatase-labelled synthetic oligonucleotide probe was applied to detect the structural gene of cholera enterotoxin (ctx). This DNA probe has a complementary base sequence to 30 base of the CT-A subunit. This method was, for the first time, applied to diagnosis of a diarrheal patient. The probe detected ctx rapidly and simply as compared with reversed passive latex agglutination (RPLA) and Beads-ELISA. The cfu minimal dose for detection with the probe was about 10(6-7)/ml. This method can be easily performed in any clinical laboratory because the procedure is safe, simple and rapid (it can be completed within about 3 hours). PMID- 1294671 TI - [Human lymphocyte proliferative response and gamma-interferon production to Pneumocystis carinii antigen in vitro]. AB - In vitro proliferative response and gamma-interferon (IFN-gamma) production to Pneumocystis carinii antigen were investigated in peripheral blood mononuclear cells (PBMC) from healthy volunteers and cord blood mononuclear cells (CBMC) from umbilical cords after delivery. Twenty three of 25 samples of PBMC had strong proliferative response, and 15 of 25 samples of PBMC produced IFN-gamma. In the samples showing strong proliferative response, CD4 lymphocytes expressed interleukin 2 receptors. None of the 3 CBMC samples had proliferative response nor production of IFN-gamma. When CD4 lymphocytes were depleted in PBMC, the proliferative response was markedly decreased and IFN-gamma production was abolished. In conclusion, the lymphocytes of healthy adults are activated and produce IFN-gamma by stimulation with P. carinii antigen, and these two response are both induced by CD4 lymphocytes. PMID- 1294672 TI - Aerobic and anaerobic bacterial interactions in the development of anaerobic bacterial pneumonia. AB - The interactions between aerobic and anaerobic bacteria in the development of anaerobic bacterial pneumonia were studied by introducing Bacteroides fragilis and Escherichia coli alone or in combination into guinea pigs by tracheal infusion. The lung lesions induced by B. fragilis were mainly located near the pleura, unlike those induced by E. coli, and were accompanied by pneumonia, lung abscess, and pleuritis. The lung lesions produced by mixed infection with B. fragilis (10(9) cfu) and E. coli (10(7) cfu) were significantly more severe than those induced by either microbe alone, and the redox potentials at the foci of inflammation were markedly reduced (max: -330 mV). Analysis of lung lesions after treatment with aztreonam and clindamycin and neutrophil phagocytic activity suggested that E. coli was primarily responsible for the lung lesions and that B. fragilis promoted the accompanying inflammation, resulting in increased pathogenicity of the mixed infections. PMID- 1294673 TI - [Rapid and direct detection of Mycobacterium tuberculosis complex and mycobacteria in sputum by advanced method, PCR]. AB - We developed two PCR methods, which amplify bovine tuberculous MPB70 gene and mycobacterial 16S rRNA gene, for detection of tubercle bacilli and mycobacteria in sputum, respectively. Among 27 Mycobacterium species and 57 species of 30 genuses other than Mycobacterium, only M. tuberculosis (TB) complex, i.e., M. tuberculosis, M. bovis, M. africanum, M. microti showed DNA amplification by PCR for MPB70, and amplification of 16S rRNA gene were observed specific in Mycobacterium species. A combination of these PCR abilities were available to differentiate the TB complex and nontuberculous mycobacteria (NTM). We investigated the correlation between these methods and conventional methods with 311 sputa that were suspected mycobacteriosis. The PCR method could detect 12 cases of TB complex and 4 cases of NTM in 17 specimens, which were positive by conventional methods, but could not for one specimen. Among 294 specimens that were negative with conventional methods, the PCR method detected 13 and 8 cases of TB complex and NTM, respectively. These results were confirmed by commercial tuberculous specific DNA probe or investigation of the clinical background of the patients. On the other hand, 273 specimens showed negative result either PCR nor conventional methods. The PCR method did not detect tuberculous DNA in normal 197 sputa, which were not suspected mycobacteriosis. These results indicate that each one of these PCR methods is highly specific to TB complex or Mycobacterium species. We concluded that these PCR methods are useful and advanced methods for rapid and direct detection of tuberculosis and mycobacteriosis. PMID- 1294674 TI - [A case of organizing pneumonia which had to be treated with steroids in the early phase of the disease against delayed resolution of severe pneumonia occurring even after antibiotic therapy]. AB - A 58-year-old male was referred to our division because of antibiotic-resistant pneumonia. A chest X-ray film revealed severe pneumonia over the left lung field but laboratory data showed no leukocytosis. Transbronchial lung biopsy findings showed the evidence consistent with organizing pneumonia. One-month prednisolone therapy produced a disappearance of the pneumonia shadow, but a giant bulla was found at the same site. It was considered that it was necessary to treat this case with a combination of effective antibiotics and steroids in the early phase of the disease. PMID- 1294675 TI - [SceI: an endonuclease with multiple cutting sites induces homologous genetic recombination]. PMID- 1294676 TI - [Structure and tissue-specific expression of erythroid type delta-aminolevulinate synthase: relation to erythroid-specific transcription factors]. PMID- 1294677 TI - [Hatching enzyme]. PMID- 1294678 TI - [Sarcoplasmic reticulum Ca(2+)-ATPase]. PMID- 1294679 TI - [The resolution of D- and L-amino acids by reversed-phase high-performance liquid chromatography]. PMID- 1294680 TI - Monitoring for HIV-1, HIV-2, HTLV-I sero-progression and sero-conversion in a population at risk in east Africa. AB - Thirty-three individuals from East Africa, at risk for acquiring sexually transmitted infections, were selected to be monitored over a five month period for evidence of sero-progression and/or sero-conversion for human immunodeficiency virus type-1 and type-2 (HIV-1, HIV-2), and human T cell leukemia virus type-1 (HTLV-I). Initially, all sera were reactive by at least one retroviral screening assay, but most produced negative or indeterminate results by western blot assays. Five months after the initial screening, western blot assays indicated that one individual exhibited full sero-conversion for HIV-1; one HIV-1 positive individual also became positive for HIV-2; and two subjects showed sero-progression to become HTLV-I confirmed positive. Sera from fourteen individuals produced indeterminate results by western blot for HIV-1, ten of which were previously negative; the remaining four sera exhibited reactivity to at least one additional viral specific antigen after the five months. Circulating HIV-1 antigen was not demonstrated in any of the sera but DNA isolated from one of the individuals with indeterminate results produced a positive reaction for HIV-1 by the polymerase chain reaction. PMID- 1294681 TI - Hepatitis B & D viral infections among schistosomal patients in Egypt. AB - A comparative study was done between schistosomal and non-schistosomal groups of acute and chronic HB patients to explore the possible role of schistosomiasis in predisposition to HBV and HDV infections in Egypt. The studied groups were 116 cases of acute hepatitis (78 cases without schistosomiasis and 38 cases with schistosomiasis). The second group of the study was 51 chronic HB patients (31 with schistosomiasis and 20 cases without schistosomiasis). All cases were tested for HBV markers and anti-HDV using ELISA technique. In acute hepatitis patients, the percentage of HBV infection as detected by HBsAg was significantly higher in the schistosomal group (63.15%: 24 out of 38) compared to non-schistosomal patients (37.17%: 29 out of 78) (Table 1). Also, Anti-HBs was detected in a significantly higher proportion among schistosomal group (85.71%: 12 out of 14) compared to non-schistosomal acute HB cases (44.9%: 22 out of 49) (Table 2). The infection rate of HBV (HBsAg+anti-HBs) was found to be statistically higher among schistosomal compared to non-schistosomal patients (94.73%: 36 out of 38 and 65.38%: 51 out of 78 respectively) (Table 3). As regards HDV among schistosomal and non-schistosomal patients suffering from acute HB, frequency of anti-HDV was found to be 33.33% (8 out of 24 HB cases) in schistosomal group versus 17.24% (5 out of 29 HB cases) in the non-schistosomal (Table 4). In chronic HB patients, anti HDV was present as 29.03% (9 out of 31) and 15% (3 out of 20) in schistosomal and non-schistosomal groups respectively (Table 5). But the differences between schistosomal and non-schistosomal groups, as regards delta infection (anti-HDV) among acute and chronic HB patients, were not statistically significant. From the present study, it was concluded that schistosomiasis contributes to significantly increased HBV infection and possibly also HDV infection. PMID- 1294682 TI - Pathological changes in testes and liver of male albino rats after dermal exposure to DDVP insecticide. AB - Exposure of male albino rats to DDVP insecticide at sublethal dose of 30 mg/kg/day through dermal painting for a period of 90 days didn't show any intoxication symptoms or mortality. However, cytopathological changes in testicular and liver tissues were evident. There was a positive correlation between the degree of cellular damage and the period of insecticide administration. In general, damages were prominent in rats treated for 30 days or more. Histological examination of testes showed degenerative seminiferous tubules and fewer leydig cells. Hepatic cells were congested, atrophied and showed different stages of necrobiotic changes. This suggests a great care and caution for workers during different phases of DDVP insecticide handling. PMID- 1294684 TI - Cross sectional study of schistosomiasis among military recruits in Alexandria. AB - A cross-sectional survey for schistosomiasis infection was carried out among 1170 military recruits in Alexandria. Data on prevalence-intensity of infection subjective symptoms and history of antischistosomal chemotherapy administration were collected from participants. The results confirmed the endemicity of S. mansoni and the low prevalence of S. haematobium infection in Delta region (33.1% and 1.1%) respectively. Previous antischistosomal chemotherapy administration was associated with decreased geometric mean egg count inspite the increase in prevalence. It is recommended that mass chemotherapy with praziquantel of this young active adult group would be of beneficial effect in decreasing schistosomiasis morbidity among an important large section of the community. PMID- 1294683 TI - An epidemiologic study of ovarian cancer. Part 11: Oral contraceptive use and menstrual events. AB - This work was conducted to investigate the potential risk factors which may contribute to the development of ovarian cancer. A retrospective analysis was adopted where 52 ovarian cancer cases and an equal number of a control group were obtained from the Western region of Saudi Arabia. This case-control study confirms that oral contraceptive use protects against the onset of ovarian cancer and that the decrease in the risk of the development of this disease is also directly related to the duration of use. Additionally, the study revealed a positive association between both age at menopause and hot flashes and the relative risk of ovarian cancer. On the contrary, age at menarche and premenstrual tension have been shown in this study to have no role as a risk factor in the development of ovarian cancer. PMID- 1294685 TI - Association between chronic hepatitis B carrier state and schistosomiasis. AB - A case-control study was designed to investigate the association between chronic HB carrier state and schistosomiasis infection. Four hundred bilharzial and 370 non-bilharzial individuals were included in this study. Sera from all individuals were tested for HBsAg and antibodies to delta Ag using ELISA. Chronic HB carrier rate was significantly higher among bilharzial cases (12.5%) than non-bilharzial individuals (6.2%). However no association was observed between HBs antigenaemia and intensity of schistosoma infection estimated by geometric mean of number of S. mansoni eggs/gm stools and S. haematobium eggs/10 ml of urine. Among important hepatitis associated risk factors reported were parenteral injection, dental manipulation and hospitalization. Blood transfusion seemed to have very minor role. Antibodies to delta Ag were detected in 9.6% of chronic HBsAg carriers, especially in the high titered individuals. PMID- 1294686 TI - Assessment of level of intellectual functioning among juvenile boy delinquents in Alexandria and its relation to behavioral deviance. AB - Sixty-five institutionalized boy delinquents in Alexandria aged 11 to 21 years were screened for intellectual functioning (I.Q. level) in relation to behavioral deviance. Findings revealed that the mean I.Q. score on the intelligence scale was within the average level of intelligence. The presence of behavior disorder varied insignificantly as a function of intellectual level. Results of this study do not indicate the prevalence of behavior disorders in relation to intellectual functioning in the total population of delinquent children not officially declared. However, the results could be a valid index of the demand for mental health services for the delinquent children, in whom "nonintellectual factors" (familial and psychosocial) might have a significant role in shaping their behavior. PMID- 1294687 TI - Clinical and radiologic study of the frequency and presentation of chest infection in children with severe protein energy malnutrition. AB - The association between P.E.M. and frequent and severe life threatening infections including lower respiratory tract infections have been always reported. Lack of the usual general and local signs of infection in P.E.M. makes the diagnosis difficult and sometimes only postmortem. This study evaluated the frequency of chest infections as well as the sensitivity, specificity and predictivity of different signs and symptoms of the disease in 100 children with severe P.E.M. (marasmus, kwashiorkor, and marasmic kwashiorkor). Sixty two percent of the studied children had chest infection (33% pneumonia, 29% bronchitis). Although most patients were symptomatic, yet, signs and symptoms were few and mostly non specific. Chest roentgenograms are thus mandatory in evaluating patients with P.E.M. whenever possible. The only valuable signs suggestive of chest infection in P.E.M. were tachypnea (> or = 40/min) and/or chest indrawing. Both were moderately sensitive, highly specific and predictive of the disease particularly pneumonia. Their presence thus, its indicative of the need for early institution of antibiotic therapy even before the results of chest roentgenograms. Total Leucocytic count was of little diagnostic value while contrary to the common belief that tuberculin test is usually negative in P.E.M., the use of double the usual dose of P.P.D. (i.e. 10 TU) yielded positive reaction in some of the studied patients and thus must not be omitted from the routine investigations of malnourished patients. PMID- 1294688 TI - Effect of dietary fat on serum and tissue lipids of adult rats. AB - The effect of 3 types of fat: 1) Ghee, 2) Corn oil, 3) Subsidized vegetable oil (SVO) on serum and tissue lipids was studied by using adult albino male rats mean weight 114 g. Rats fed diet containing SVO had the highest serum cholesterol and LDL-cholesterol concentrations than those fed diet containing ghee or corn oil. Serum high density lipoprotein-cholesterol (HDL) concentration was highest in animals fed the ghee and lowest with those fed the SVO diet. On the other hand phospholipids values tend to be lower when feeding diets containing oils. Also serum triglycerides levels were higher on saturated fat diet than on the unsaturated fat diets. The same trends were found for liver cholesterol as in serum cholesterol. SVO diet gave the highest liver cholesterol concentration. Also SVO gave the highest heart phospholipids values. PMID- 1294689 TI - Tumor necrosis factor (TNF alpha) in lymphadenopathy and bone marrow involvement: histopathological and serological study. AB - Serum samples were collected from 40 patients with enlarged lymph nodes. Lymph node and bone marrow biopsies were performed and processed as usual. Tumor necrosis factor-alpha (TNF alpha) was determined in the sera by factor test human TNF alpha ELISA kit. Histopathological studies of lymph node and bone marrow biopsies were evaluated. The data obtained from this study showed that bone marrow was involved in only 5 patients and their TNF showed the lowest level in this study with a mean level 50 pg/ml. The highest level of TNF occurred in cases with granulomatous lymphadenitis (124 pg/ml) followed by reactive lymphadenitis (105 pg/ml). It can be considered that TNF reflects the immune status of the patient and its study in the serum can be of help in evaluating the progress of the disease. An extended study is need to evaluate the role of TNF-alpha as a prognostic marker in malignancy. PMID- 1294690 TI - Evaluation of diagnosis of ovarian malignancy using immunohistochemical technique. AB - Immunohistochemical staining was performed on biopsy specimens from normal ovary and also from abnormal ovarian growth using monoclonal OKT9 antibody. The results showed positive reaction in 8.77% of normal ovarian specimens removed during laparotomy. The reaction was also positive in 15.7% in cases diagnosed by histological examination as benign ovarian growth. Specimens proved by histological examination to be malignant showed reaction with OKT9 in 100%. The significance of this finding is discussed. PMID- 1294691 TI - A study of the morbidity pattern of referred patients and the effectiveness of the referral system in primary health care centers. AB - Patient referral system is considered to be an important element in achieving the objectives of the Primary Health Care services. Patients attending the Primary Health Care Center (PHCC) expect basic medical care and appropriate follow-up services. Thus, patients requiring further evaluation and treatment are referred to a secondary health care facility. In this study the morbidity pattern as well as the referral system was evaluated in selected PHCC in the city of Jeddah. A systematic random sample of all the patient referrals from selected PHCC's were analyzed. A total of 1,164 referrals were studied, 59.9 per cent were females and 40.1 per cent were males. The contents of referral letters from PHCC to hospitals as well as feed back from hospitals were analyzed. The majority of referrals were for the age group 25-44 years old 458 (39.3%). The results demonstrated that 5 per cent of patients were routinely referred to the secondary health care centers, and the feedback from these secondary health care facilities was (22.7%). It was also noted that the majority of referral letters lack commonly accepted standards of information about the patient. It was concluded that the follow-up and feed-back system needs to be reinforced. The primary health care providers need to review the patient referral system and implement specific criteria for the optimum utilization of this essential service for the benefit of the community. PMID- 1294692 TI - Study of the effect of birth spacing on maternal health. AB - This study aims at identifying the effect of birth spacing on maternal health. The study was carried out on a representative sample of 324 married women at the fertile age period and having at least two children. The result of this study revealed that women practicing birth spacing were 33.3% of the studied sample. The mean age was 34.4 +/- 5.3 years and 31.3 +/- 5.7 years for improper and proper birth spacing respectively. Improper birth spacing women constituted 70.2% of low social class. Out of the total number of improper birth spaced women, 41.7% were overweight, 25.9% were hypertensive, 57.4% had varicose veins, and 18.1% had low limb oedema. Concerning Gynecological findings; vaginal discharge and cervical erosion were 70.4% and 19.4% of improper birth spacing women respectively, laboratory investigations revealed that anaemia and glucosuria were 88.4% and 12.5% of improper birth spacing women respectively. Good knowledge and favorable attitude were 88% and 100% of properly birth spaced women. The mean number of gravidity, number of abortions and number of infant deaths were 6.6 +/- 2.8; 0.9 +/- 1.3 and 1.36 +/- 1.63 of improperly birth spaced women respectively and 4.2 +/- 1.7; 0.6 +/- 1.1 and 0.41 +/- 0.81 of properly birth spaced women respectively. It could be concluded that young women were practicing birth spacing more properly. Rural origin women are less practicing birth spacing. Medical and Gynecological disorders were more among improper birth spacing women. Pregnancy wastage are more among improper birth spacing. It is to be recommended that more efforts should be done among low social class. Encouraging young women to practice pre-natal care. Emphasizing on the practice of proper birth spacing and small family size. PMID- 1294693 TI - Phospholipase A2 inhibitors from marine organisms. AB - This review of phospholipase A2 (PLA2) inhibitors from marine organisms presents a compilation of research in this field over the past decade. As an introduction to the research on marine natural products, there is an overview of the role of PLA2 in inflammation that provides a rationale for seeking inhibitors of PLA2 as anti-inflammatory agents. A radiometric assay to measure inhibition of bee venom PLA2 is described in detail. Examples of marine natural products that inhibit PLA2 are manoalide and its derivatives, scalaradial and related compounds, the pseudopterosins, the vidalols, and a group of terpenoids that contain masked 1,4 dicarbonyl moieties. PMID- 1294694 TI - Strategies and tactics for the synthesis of oxygenated natural products. AB - The total synthesis of the ansa antibiotic macbecin I [1] is described exploiting an approach that features the oxidative transformation of furans into hydropyrans that then serve as conformationally biased templates for stereoselective refunctionalization and elaboration. A novel variant of the Mitsunobu reaction was developed that may be applied to the inversion of hindered secondary alcohols. In work directed toward the total synthesis of the antifungal antibiotic ambruticin [3], new and general methods have been invented for the asymmetric synthesis of functionalized cyclopropanes by intramolecular cyclopropanations of omega-unsaturated diazoacetates and the convergent stereoselective synthesis of trisubstituted alkenes. PMID- 1294695 TI - Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis. AB - The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor. PMID- 1294696 TI - Isolation of picropolygamain from the resin of Bursera simaruba. PMID- 1294697 TI - Cytotoxic activity of tetraprenylphenols related to suillin, an antitumor principle from Suillus granulatus. AB - Cytotoxic activity against three tumor cell lines (KB, P-388, and NSCLC-N6) has been determined for 14 natural and semisynthetic tetraprenylphenols. Structure activity relationships have been examined. PMID- 1294698 TI - Anti-tumor-promoting activities of afromosin and soyasaponin I isolated from Wistaria brachybotrys. AB - Afromosin [1] and soyasaponin I [2] isolated from Wistaria brachybotrys exhibited remarkable inhibitory effects on mouse skin tumor promotion, and afromosin also exhibited a significant inhibitory effect on pulmonary tumor promotion. The combined effects of these compounds on the two-stage skin carcinogenesis were also examined, and it was concluded that the combination of 1 with 2 enhanced the inhibitory effect. PMID- 1294699 TI - Identification of the new 10,15-eicosadienoic acid and related acids in the opisthobranch Haminaea templadoi. AB - The free fatty acids of the Mediterranean opisthobranch Haminaea templadoi were isolated and characterized, revealing the presence of the new 10,15-eicosadienoic acid [1] and several unusual cis delta 6 monoenoic acids, such as (Z)-6 tetradecenoic acid, (Z)-6-pentadecenoic acid, and (Z)-6-heptadecenoic acid. These results reveal some previously unrecognized fatty acids in mollusks. PMID- 1294701 TI - Distribution of circulating beta-carotene in human plasma lipoproteins. AB - We examined the distribution of beta-carotene in plasma lipoprotein fractions. In healthy children and adults, LDL contained more beta-carotene than did HDL, but in cord blood more beta-carotene was found in HDL than in LDL. After the oral administration of beta-carotene, its plasma level rose although its distribution in the individual lipoprotein fractions did not change. Among disease conditions associated with hyperlipidemia, the ratio of beta-carotene to plasma lipids was highest in anorexia nervosa, while nephrotic syndrome and diabetes mellitus had similar ratios to each other. PMID- 1294700 TI - Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra. AB - Five sesquiterpenoids containing isonitrile or isothiocyanate groups were isolated from the sponge Acanthella klethra. Compounds 1 and 2 were identified as axisonitrile 3 and the corresponding isothiocyanate derivative, respectively. Compounds 3-5 were found to be eudesmane sesquiterpenes. None of these compounds was cytotoxic toward cultured KB-3 cells, but varying degrees of activity were observed with cultured Plasmodium falciparum. Compound 1 demonstrated greatest promise as an antimalarial agent. PMID- 1294702 TI - High-performance liquid chromatographic separation and spectral identification of the photoreaction products of methyl 5,8-epoxyretinoate. AB - Photoreaction of methyl 5,8-epoxyretinoate was investigated. Irradiation of methyl 5,8-epoxyretinoate in acetonitrile with a light from a high-pressure mercury lamp or a daylight fluorescent lamp afforded three new products, which were purified by high-performance liquid chromatography. They were characterized on the basis of spectroscopic data as 11-(Z), 13-(Z), and 11,13-di(Z) isomers, respectively. PMID- 1294703 TI - Determination of absorption and endogenous excretion of iron in man by monitoring fecal excretion of a stable iron isotope (58Fe). AB - The absorption and endogenous excretion of iron in man was studied by monitoring the fecal excretion of a stable iron isotope (58Fe). The study was carried out for 12 healthy volunteers who were divided into two groups. Group I received 58Fe labeled ferric ammonium citrate (III) (58FeAC) equivalent to 6 mg of iron as a control, and group II received a combination of 500 mg of vitamin C and 58FeAC. A new formula was used to calculate the 58Fe absorption ratio reflecting the pool of iron in the intestinal cells, and the ratio was compared with that obtained from Janghorbani's formula, which has been used as one of the common methods. As a result, the 58Fe absorption ratio in group II was statistically significantly higher than that of group I (34.4 +/- 6.1% vs. 15.0 +/- 5.5%, M +/- SD) using Janghorbani's formula. The similar absorption ratio (34.1 +/- 6.0% vs. 14.8 +/- 5.5%) was also obtained by our new formula. Our results confirmed the previous findings that the availability of iron is stimulated by the supplementation of vitamin C. Both formulae agreed in the absorption of iron, indicating that the endogenous excretion of iron (caused by the desquamated cells) in the intestine does not disguise the iron absorption. PMID- 1294704 TI - Impact of lead toxicity on brain metabolisms of nucleic acid and catecholamine in protein malnourished rats. AB - The brain biochemistry in terms of certain key substances of brain were studied in 18% protein and 6% protein-fed rats following lead ingestion at a level of 1% in the diet. Lead ingestion diminished the protein and increased the RNA content of brain, and, consequently reduced the protein/RNA ratio. The RNA/DNA ratio in brain was elevated in lead toxicity, while the protein/DNA ratio remained unaltered. The RNase and DNase activities of brain were decreased. Lead treatment diminished the glutathione (GSH) level of blood but the GSH level of brain was not altered significantly by the lead treatment. The plasma protein level was also diminished after lead treatment. The effects of lead on some of these parameters were found to be more pronounced in rats receiving the 6% protein diet. The serotonin (5-HT) level of brain was reduced, while the norepinephrine (NE) and dopamine (DA) levels of brain were elevated following lead treatment. The monoamine oxidase (MAO) and tryptophan hydroxylase (TPH) activities and 5 hydroxy-indole acetic acid (5-HIAA) content of brain were elevated in lead ingested rats. The effects of lead on these parameters were found to be potentiated when the rats were fed on a 6% protein diet. These studies suggest that lead at the present dose affects brain biochemistry in terms of both nucleic acids and amine metabolism, and protein deficiency potentiates some of these lead induced changes. PMID- 1294705 TI - Lipophilic soluble protein represents labile protein in rat liver. AB - Lipophilic proteins, having higher turnover rates than the average of the total soluble protein pool, were separated from soluble rat-liver proteins on alkyl agarose column. The quantitative immunoprecipitation, using the antibody against the lipophilic proteins, showed that the soluble proteins from the liver of fed rats contained about twice as much lipophilic proteins as that of 3-day-starved rats. This result indicates that the lipophilic proteins, at least in part, represent labile protein in rat liver. PMID- 1294706 TI - The effect of dietary safflower phospholipid and soybean phospholipid on plasma and liver lipids in rats fed a hypercholesterolemic diet. AB - The effect of dietary safflower phospholipid (Saf-PL) and soybean phospholipid (Soy-PL) on plasma, liver, and fecal lipids in rats fed a hypercholesterolemic diet was compared with that of triglyceride mixture (controls). Triglyceride mixture (SP-Oil) of safflower oil and palm oil (8:2) contained almost comparable amounts of linoleic acid to safflower phospholipid or soybean phospholipid. Concentration of total cholesterol in plasma of rats fed the Saf-PL and Soy-PL diets were significantly decreased in comparison with that of the SP-Oil diet. Similarly, both Saf-PL and Soy-PL induced a reduction in the concentration of liver cholesterol compared with SP-Oil; Saf-PL indicated the lowest value. Saf-PL only significantly increased the level of high density lipoprotein (HDL) cholesterol. The level of chylomicron plus very low density lipoprotein (VLDL) cholesterol was lower in rats fed the Saf-PL and Soy-PL diets than that of the SP Oil diet. The activity of plasma lecithin-cholesterol acyltransferase (LCAT) was increased in rats fed Saf-PL and Soy-PL. Saf-PL and Soy-PL caused an enhanced excretion of fecal neutral steroids, but not acidic steroids compared with SP Oil. These results suggest that, in addition to soybean phospholipid, safflower phospholipid suppresses the elevation of plasma and liver cholesterol and that this effect may be brought about by inhibiting the absorption of cholesterol in the small intestine. PMID- 1294707 TI - Hemoglobin repletion in anemic rats fed a new bean cultivar (Phaseolus vulgaris L.) as source of iron. AB - Utilization of iron from a new cultivar of dry bean (Carioca 80 SH) was estimated using anemic rat by two methods: the slope ratio and the hemoglobin regeneration methods. The bean was incorporated into the diet in the form of whole bean flour (WBF) 7.45 mg Fe/100 g or as partially decorticated bean flour (DBF), 8.57 mg Fe/100 g. Hemoglobin concentration in the rats' blood at the beginning of the experiment averaged 13.79 +/- 0.33 g Hb/dl; at the end of the depletion period it ranged from 5.62 +/- 0.38 to 6.30 +/- 0.39 g Hb/dl blood, difference which was not statistically significant (p < or = 0.05). The bean iron relative biological value (RBV, relative to FeSO4 = 100) evaluated by the slope ratio method, was 74% for the WBF and 77% for the DBF. The hemoglobin regeneration efficiency was 60.4 +/- 6.5, 50.8 +/- 3.2, and 52.7 +/- 5.7%, respectively, for the iron sulfate (reference source), the WBF, and the DBF. PMID- 1294708 TI - Obligatory nitrogen losses in pregnant rats with special reference to estimation of net protein utilization. AB - For estimation of net protein utilization of dietary proteins during pregnancy, obligatory nitrogen losses were measured in protein-deficient rats in which pregnancy was maintained by administration of ovarian steroids. On shift from normal to protein-free diet, urinary nitrogen, expressed as mg/day or mg/100 g BW per day, decreased initially rapidly and then gradually during the first two weeks in both pregnant and nonpregnant rats. However, urinary endogenous nitrogen increased during the final week of pregnancy, whereas it continued to decrease in nonpregnant controls. The endogenous urinary nitrogen excretions during early-mid and late pregnancies were significantly higher in pregnant rats (666 mg/15 days and 234 mg/6 days, respectively) than in nonpregnant animals (585 mg/15 days and 153 mg/6 days, respectively), indicating pregnancy-induced protein hypercatabolism. The metabolic fecal nitrogen excretions in pregnant and nonpregnant rats were comparable. In pregnant rats, a protein-free diet resulted in decrease of basal energy expenditure, from 24 kcal/day on day 1 to about 15 kcal/day on days 16, 19 and 22 of pregnancy. Thus, the ratio of endogenous urinary nitrogen to basal energy expenditure increased in late pregnancy, indicating that "the law of a constant relationship of minimal nitrogen and energy output" is not applicable to the pregnant animals. We discuss which values for obligatory nitrogen loss should be used for estimating the net utilization efficiency of dietary proteins in pregnancy. PMID- 1294709 TI - Net utilization of various levels of whole egg protein in pregnant rats. AB - Net protein utilization (NPU) was examined in pregnant rats fed various levels (1, 3, 6, 10 and 20%) of whole egg protein (WEP), based on their obligatory nitrogen losses. On increase in dietary protein, nitrogen balance improved curvilinearly and the NPU decreased exponentially in both pregnant and nonpregnant rats. The utilization efficiency was high in rats fed marginally low protein diets, mainly due to lower urinary nitrogen levels than the obligatory levels of nitrogen loss. The NPUs in pregnant rats fed 1, 3, 6, 10 and 20% WEP diets were 103, 99, 78, 66 and 46, respectively. These values were 15 to 20% higher than those in nonpregnant rats because in pregnant rats obligatory urinary nitrogen loss was higher and the animals took more energy. The problems in application of the NPUs in pregnant rats for estimating the protein allowance of pregnant humans are discussed. PMID- 1294710 TI - Umbilical ascorbic acid levels in fetal distress. AB - Umbilical arterial and venous blood samples were obtained at birth immediately after clamping the cord in 38 infants. Simultaneously, maternal arterial samples were collected. Arterial blood samples were analyzed for acid-base blood gas content and venous blood samples were analyzed for plasma ascorbic acid levels. The umbilical plasma ascorbic acid level was significantly higher when compared with maternal plasma levels (172.9 +/- 39.2 vs. 57.8 +/- 21.0 mumol/liter, p < 0.0001). Correlations between maternal ascorbic acid levels and umbilical cord levels proved to be insignificant. Umbilical ascorbic acid levels in the 2 groups of infants characterized by the presence or absence of fetal distress showed significantly higher levels in the fetal distressed group (17 infants) when compared to the non-distressed group (21 infants)--191.9 +/- 36.0 vs. 157.4 +/- 34.6 mumol/liter, p < 0.005. The use of an umbilical cord ascorbic acid cut-off point of 95.8 mumol/liter gave a sensitivity of 76% and a specificity of 67% as predictors for the presence or absence of fetal distress (p < 0.025). The results of the present study demonstrate a substantial increase in ascorbic acid levels in infants exposed to intrapartum fetal distress, without any clinical sign of such insult at or after birth. PMID- 1294711 TI - A simple enzymatic quantitative analysis of triglycerides in tissues. AB - We determined a method to measure the triglyceride levels in tissues by using a modified enzymatic kit. This enzymatic kit was originally designed to be used to measure the triglyceride levels in plasma. Our method of triglyceride level determination includes dissolving the tissue lipid extracts in an alcohol. Before using the enzymatic kit directly, the lipids were dissolved in tert-butyl alcohol, then a Triton X-100/methyl alcohol mixture was added (1/1 by volume). The presence of organic surfactants such as tert-butyl alcohol and methyl alcohol, and of a surfactant such as Triton X-100, did not interfere with the enzymatic activity. This method enabled us to determine triglyceride levels between 10 and 90 nmol, by using a spectrophotometer to measure the absorbances. PMID- 1294712 TI - The morphological and biochemical changes in skeletal muscle fibers by dietary protein restriction. AB - The effects of dietary protein restriction on skeletal muscle fibers were studied according to morphological and biochemical approaches. Protein and DNA content of quadriceps muscles from young adult rats were decreased by the low protein and protein-free diet. Morphological examination demonstrated that there was a significant decrease in the size of muscle fibers without change in their numbers due to protein restriction. The protein/DNA ratio, accepted as an index of cell size in biochemical approaches, was compared with cell size on photomicrographs. Actual fiber size appeared much smaller than that indicated by the protein/DNA ratio. PMID- 1294713 TI - Thiamin triphosphate does not affect contraction of skinned fibers. AB - Effects of thiamin triphosphate (TTP) on contraction of chemically skinned fibers prepared from the extensor digitorum longus muscle of guinea pigs were investigated. The addition of TTP at 40 microM concentration affected neither Ca2+ uptake nor Ca(2+)-induced Ca2+ release by sarcoplasmic reticulum. Contraction of myofibril was not affected by TTP either. PMID- 1294714 TI - [Structural studies of malaria vaccine]. AB - Malaria still remains a serious health problem in large areas of the world, and in this article, recent research progress mainly made by us toward malaria vaccine development has been reviewed. 1) Peptide vaccines (antigens) of immunodominant tetrapeptide repeats (NANP and NVDP) of the circumsporozoite surface protein of the malaria parasite, Plasmodium falciparum, were genetically produced in E. coli as a fusion protein with a part of human growth hormone, which has affected on the conformations and immunogenicities of the peptide vaccines. 2) Monoclonal antibodies against the peptide antigens were produced by fusion of mouse spleen cells with myeloma cells, and the F (ab's) obtained by partial digestion of the antibodies with papain were used for the measurement of the dissociation constants of the antigen-antibody complexes. The amino acid sequence of the Hv region in F(ab) domain was also deduced from its nucleotide sequence. PMID- 1294715 TI - [Studies on the mechanism of drug distribution in tissues]. AB - The importance to elucidate the mechanisms of drug distribution in tissues has been discussed in this review. By considering several factors such as tissue binding, plasma binding, membrane permeability and tissue interstitial fluid space, the tissue distribution states of drug have been characterized based on the biochemical and pharmacokinetic studies. These physiological pharmacokinetic analyses have been applied to evaluate the determinant factors of inter-organ, drug to drug, interspecies or age related changes of tissue distribution of drug. The mechanisms of membrane permeability of drug which could play the most important role to regulate the drug distribution have been discussed. The drug distribution to the brain is strictly restricted by the function of the blood brain barrier (BBB). The drug transport mechanisms at the BBB have been discussed. Especially, the role of carrier-mediated and absorptive-mediated transport systems at the BBB has been focused on. PMID- 1294716 TI - [Quenching of ethidium-DNA fluorescence by novel acridines with antitumor activities]. AB - In order to elucidate the relationships between the antitumor activity and the molecular structure of novel acridine derivatives (1a-f, and 2a-e in Chart 1) the DNA-binding properties (intercalation) of the derivatives were examined by the quenching in fluorescence of an ethidium-DNA complex, which may be caused by the displacement of DNA-bound ethidium by a second DNA-binding ligand, acridines. The concentration (C50 value) of the acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The fluorescence quenching of the acridines was examined using 4'-(9-acridinylamino)- methanesulfonanilide (amsacrine, AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pairs. PMID- 1294717 TI - [Activity of Enterococcus faecalis (FK-23) preparation as a biological response modifier]. AB - The biological activity of a preparation of heat killed cells of Enterococcus faecalis, FK-23 which was isolated from the feces of a healthy human, was investigated in C3H/He mice. Intraperitoneal injection of the preparation caused an accumulation of neutrophils and macrophages in the peritoneal cavity of the mice 6 h later. As a parameter of the activation of macrophages, the effect of the FK-23 preparation on the production of tumor necrosis factor (TNF) was examined. The mice were given two consecutive intravenous injections of the preparation at a dose of 10 micrograms/mouse and, 3 h later, of 300 micrograms/mouse. The TNF level in the sera reached 99 U/ml in mice 2 h after the second injection. This preparation also stimulated peritoneal macrophages to produce TNF in vitro and increased the capacity of neutrophils to adhere to plastic plates and to release active oxygens, but did not induce blastogenic transformation of lymphocytes. These results suggest that the FK-23 preparation is a biological response modifier (BRM) with various activities on phagocytes similar to a streptococcal antitumor agent, OK432. PMID- 1294718 TI - [Effects of ascorbic acid on the metabolic fate and the free radical formation of iproniazid]. AB - The effects of ascorbic acid (AA) on the metabolic fate of iproniazid (IPN) and on the free radical intermediates derived from IPN were investigated in rats. After oral administration of IPN with or without AA, the plasma concentration and the urinary excretion of IPN and its metabolites were determined by gas chromatography-mass spectrometry using stable isotope labeled compounds as internal standards. In the excretion of IPN and its metabolites except hydrazine (Hy), the differences between co-administration and single administration were not observed. The excretion of Hy, which is a known hepatotoxic metabolite, decreased clearly in the co-administration of IPN and AA. When IPN and AA were co administered orally, the profiles of plasma levels of IPN and its metabolites were almost similar after the administration of IPN alone. Furthermore, no differences between i.v. co-administration and i.v. administration alone were observed. These results indicated that AA did not affect both absorption and metabolism of IPN. By the electron spin resonance (ESR) spectroscopy and spin trapping technique, the ESR signals due to the alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (4-POBN) adducts induced by isopropylhydrazine (IP-Hy) were two-fold higher than those by IPN in microsomal systems. The free radical formations of IPN and IP-Hy were significantly inhibited by AA in a dose dependent manner. The 4-POBN-trapped radical species generated from IPN and IP-Hy were presumed to be an isopropyl radical by the results of mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294719 TI - [Antimutagenic substances in the Armeniacae semen and Persicae semen]. AB - Using the Ames/Salmonella/microsome assay, we examined the antimutagenic effect of the hexane extract of Armeniacae semen (apricot (Prunus armeniaca L.) seed), Persicae semen (peach (P. persica Bat.) seed), and seeds of cherry (P. avium L.), plum (P. salicina Lindle) and almond (P. dulcis Mill). Hexane extracts of Armeniacae semen and Persicae semen inhibited the mutagenicity of benzo[a]pyrene (B[a]P), but those of seeds of cherry, plum and almond did not. The mutagenicities of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-(2 furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) were also inhibited by the extracts of Armeniacae semen and Persicae semen. Inhibitory substances in Persicae semen were fractionated by silica gel column chromatography and high performance liquid chromatography, and were identified as oleic acid and linoleic acid. The contents of oleic acid and linoleic acid were 0.7 and 0.4% in the hexane extract of Armeniacae semen, and 1.5 and 0.5% in that of Persicae semen, respectively. PMID- 1294721 TI - [Endoluminal echography, major axis of progress in imaging]. PMID- 1294720 TI - [Determination of scopolia extract in commercial gastrointestinal drugs by high performance liquid chromatography]. AB - Tropane alkaloids, contained in gastrointestinal drugs including Scopolia Extract, were determined using high-performance liquid chromatographic method. Tropane alkaloids in commercial drugs were extracted with 0.5 N hydrochloric acid test solution. This solution was adjusted to pH 10.0 with a strong ammonia solution, extracted with ethyl ether, and separated on TSKgel ODS-120T (4.6 mm i.d. x 15 cm; temperature, 30 degrees C; flow rate, 1.5 ml/min; detector, UV 210 nm) with a mixture of 1/15 M sodium phosphate buffer (pH 2.5) and acetonitrile (68:32) containing 12 mM sodium dodecyl sulfate. The contents of atropine in the gastrointestinal drugs were 0.25-0.34 mg (coefficient of variation = 0.20-2.61%) a day. PMID- 1294722 TI - [Contrast media in hepatic MRI]. AB - This article is a review of the current commercial MR contrast media (gadolinium chelates) and of the products that are not yet on the market and are under trial in man (super-magnetic iron oxides, manganese compounds) or only in animals (ferric chelate, liposomes containing gadolinium compounds, gadolinium chelate/human serum albumin compounds, hepatic asialoglycoprotein receptors). PMID- 1294723 TI - [Imaging of HIV+ abdominal involvements]. AB - Abdominal symptoms are among the most frequent complaints of patients with AIDS. Because precise diagnosis from symptoms alone is difficult, the contribution of radiologist is important to fill in evaluating the cause of various illnesses. The review describes common clinical symptoms and lists the most likely causes with discussing the most appropriate imaging evaluation. For diagnosis and treatment, the most frequent and characteristics radiographic findings are described. PMID- 1294724 TI - [Interstitial pulmonary involvements in polymyositis and dermatopolymyositis. Apropos of 3 cases. Review of the literature]. AB - The authors report 3 cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti Jol antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis. PMID- 1294725 TI - [Anguilluliasis of the small intestine and AIDS. A case and review of the literature]. AB - The authors report about one patient with an Acquired Immune Deficiency Syndrome (AIDS) presenting with strongyloidiasis involving the small bowel. On the basis of this observation, they describe the appearances of small bowel involvement by strongyloidiasis in patients with AIDS. They emphasize the main features differentiating these cases from the usual affection, namely the severity and diffusion of the lesions, as well as the presence of a very extensive associated lymphoid nodular hyperplasia. PMID- 1294726 TI - [Breast microcalcifications]. AB - Microcalcifications of the breast are better recognized as the quality of mammographs is improving. The clinical examination and complementary modalities are often essential to evaluate their significance and point out to an indication for surgery. However, especially when the microcalcifications are detected during a systematic examination, a strict analysis of mammographs is essential. The number of useless punctures must be reduced, as their psychological impact and socioeconomic weight are already demonstrated. Although there is no consensus, most recent publications contain ideas converging on the selection of the indications for a histological control on the basis of an accurate semiological study. PMID- 1294727 TI - [Ultrasonographic aspects of hemolytic uremic syndrome in children. Apropos of a series of 21 cases]. AB - The sonographic expression of the hemolytic-uremic syndrome in children is a cortical hyper-echogenicity, which has a real prognostic value in comparison to the clinical criteria. In addition, renal ultrasonography with Doppler is useful to predict the evolution of the condition, and may help the clinician to define the therapeutic choices. PMID- 1294728 TI - [Merkel cell tumor. Contribution of imaging apropos of a case]. AB - This rare malignant skin tumor, of controversial origin, possesses marked potential for dissemination. A case is reported in which medical imaging technics allowed close surveillance of the course of the disease. PMID- 1294729 TI - [Chordoma of the base of skull. Apropos of 3 cases]. AB - The authors report 3 cases of skull base chordomas. In 2 cases, skull radiographies and computed tomography found lytic lesions of sphenoid and clivus, with calcifications into the tumors. In the third case, radiological findings suggest a naso pharynx tumor. PMID- 1294730 TI - [Radiological study of firearm projectiles. 3: Projectiles for sifled firearms]. PMID- 1294731 TI - Changing perspectives in the treatment of rheumatoid arthritis. PMID- 1294732 TI - Systemic lupus erythematosus and the antiphospholipid syndrome: reflections about the relevance of ARA criteria. PMID- 1294733 TI - Localization of the enzyme neutral endopeptidase to the human synovium. AB - Neuropeptides, contained within sensory nerve fibers in the synovium, are present in inflammatory joint fluids. The potency of these peptides in vitro has led to the hypothesis that enzyme degradation systems are operative in vivo. To address this question we localized neutral endopeptidase (NEP; EC 3.4.24.11) in human synovium. The normal human synovium failed to show any immunoreactivity for NEP. In the disease groups there was intense staining of cells surrounding blood vessels. Our data are consistent with the hypothesis that a proportion of synovial fibroblasts are the major source of this enzyme in the arthritic joint. PMID- 1294734 TI - Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: I. Nonsteroidal antiinflammatory drugs. AB - The probability of continuation of a particular nonsteroidal antiinflammatory drug (NSAID) over 5 years was estimated for 1,775 courses taken by 532 patients with rheumatoid arthritis treated in 7 rheumatology private practices. Similar results were seen for 15 different NSAID--48% of courses were continued at 12 months, 36% at 24 months, and 20% at 60 months. Only acetylated salicylates, other than plain aspirin, were continued significantly longer than any of the other NSAID. The probability of continuation of plain aspirin was similar to other NSAID, including nonacetylated salicylates and nonsalicylate NSAID. The first NSAID taken by an individual patient was continued only marginally longer than the 4th NSAID taken by the same patient. While most NSAID courses were not continued for long periods, 20% were continued for longer than 5 years, suggesting effective longterm results in this minority of courses. PMID- 1294735 TI - Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. AB - The probability of continuation of 1,077 courses of 2nd line drugs taken by 532 patients with rheumatoid arthritis treated in 7 rheumatology private practices was examined. This probability was that 50% of courses were continued over 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate (MTX). MTX and prednisone were the only drugs continued by more than 50% of patients after 60 months, while about 20% of courses of other 2nd line drugs other than oral gold were estimated to be continued at 60 months. Estimated drug continuation did not differ significantly according to age, duration of disease, or whether the drug was the first, second, or 3rd 2nd line drug used. Some patients took each 2nd line drug for more than 5 years, suggesting a favorable experience, but most courses were not continued beyond 2 years. PMID- 1294737 TI - Relationship of changes in helplessness and depression to disease activity in rheumatoid arthritis. AB - We investigated the relationship between changes in helplessness and depression to disease activity in rheumatoid arthritis (RA). Sixty-three men with RA were examined at baseline, 3 months, and 6 months. Joint counts, immunophenotypic analyses of peripheral blood lymphocytes, and measures of psychological status were obtained at each examination. Zero-order correlations between psychological change and disease activity change from baseline to 6 months were not significant, but hierarchical multiple regression analyses revealed that changes in affective state were significantly related to joint counts at 6 months. Additionally, changes in absolute numbers of HLA-DR+ (human leukocyte antigen DR type) cells were significantly related to joint counts at 6 months. When absolute numbers of HLA-DR+ cells were entered prior to affective state in a hierarchical multiple regression, affective state was only marginally statistically significant. The study shows that longitudinal relationships between affective changes and disease activity are moderated by intervening variables such as immunologic activation. PMID- 1294736 TI - Sex hormones and bone metabolism in postmenopausal rheumatoid arthritis treated with two different glucocorticoids. AB - To investigate the effect of low doses of 2 different glucocorticoids on bone mass, sex hormone status and bone metabolic indices, a study was undertaken in 16 postmenopausal women with rheumatoid arthritis (RA) receiving < 15 mg/day of deflazacort and in 16 patients with RA matched for age, years postmenopause and disease duration, receiving < 10 mg/day of prednisone. Sixteen healthy postmenopausal women and 16 nonsteroid treated patients with RA were also studied as control groups. Vertebral bone density (vBMD) was lower (mean +/- SD: 0.65 +/- 0.07 vs 0.73 +/- 0.09 g/cm2; p < 0.02) in prednisone treated patients than in deflazacort treated patients, whose vBMD values were similar to those of nonsteroid treated RA. No significant difference was found as for radial bone mineral content. Circulating levels of estradiol, dehydroepiandrosterone sulfate, androstenedione and progesterone were low in all patient groups with RA when compared with healthy controls. The prednisone treated patients showed significantly lower values of all sex hormones with respect to deflazacort treated patients. Osteocalcin values were also lower (3.0 +/- 1.4 vs 3.9 +/- 1.6 ng/ml; p < 0.05) in prednisone treated patients with respect to deflazacort treated group. Glucocorticoid treated patients showed a direct correlation (r2 = 0.39) between vBMD and plasma estradiol levels, while no correlation was found with osteocalcin values. In conclusion, our postmenopausal patients with RA treated with low dose prednisone had reduced levels of sex hormones and osteocalcin and reduced vertebral bone mass. Comparable doses of deflazacort showed only a mild inhibitory effect on sex hormones and osteocalcin, and did not show any detectable effect on bone mass. PMID- 1294738 TI - Severity of disability and duration of disease in rheumatoid arthritis. AB - A longitudinal sample of patients with rheumatoid arthritis (RA) from Santa Clara County, CA was analyzed. Severity was measured with the Disability Index from the Health Assessment Questionnaire (HAQ). First, 6 cohorts were created of women and men with 0 to 10, > 10 to 20, and > 20 years of duration of illness in 1981. Experiences of the 6 cohorts were studied from 1981 to 1989. For both sexes, and both samples which alternately included and excluded the deceased, persons with > 20 years of duration experienced faster deterioration than those with < 20 years. Second, multiple regression models were estimated which treated the Disability Index as the dependent variable. In the regression models, the Disability Index worsened more quickly for women than men, for persons with few rather than many years of education, and for older than younger persons. Regression models which excluded an intercept term suggested a unique "S" shaped curve that described the Disability Index and duration relation. PMID- 1294739 TI - The sense of coherence questionnaire in patients with rheumatic disorders. AB - Aaron Antonovsky's Sense of Coherence (SOC) questionnaire with its 3 subscales is designed to measure strengths within individuals that allow them to survive in the face of extreme stresses, including chronic illness. We administered the SOC to 1333 patients with rheumatic disorders. Although the instrument had high alpha reliability, factor analysis did not support the concept of distinct subscales. The SOC was strongly related to the Arthritis Impact Measurement Scales anxiety and depression scores (r = -0.63 to -0.69), less strongly related to clinical variables (r = -0.20 to -0.33), and was minimally related to demographic variables. When psychological variables were controlled for, almost no association between the SOC and clinical variables remained (r = 0.06). Whether the SOC will be more useful than standard psychological instruments awaits the result of ongoing studies. PMID- 1294740 TI - Autoantibodies versus clinical symptoms in blood donors. AB - A group of 255 blood donors was analyzed for the presence of serum autoantibodies, e.g., antinuclear antibodies, smooth muscle antibodies, antimitochondrial antibodies, antiparietal cell antibodies and antireticulin antibodies by indirect immunofluorescence microscopy. The 37 (15%) who had autoantibodies underwent examination and extended laboratory investigation. We found no strong evidence of disease in any of the blood donors with autoantibodies. PMID- 1294741 TI - Absence of HLA-B8 and HLA-DR3 in Japanese patients with Sjogren's syndrome positive for anti-SSA(Ro). AB - Forty Japanese anti-SSA(Ro) positive patients with Sjogren's syndrome were typed for HLA-A, B, C, DR and DQ antigens. No patient had either HLA-B8 or HLA-DR3 which has been reportedly associated with the immune response to SSA(Ro) antigens in white and black patients. Our patients had higher frequencies of HLA-DRw8 and HLA-DRw52 than the control population. PMID- 1294742 TI - Fibroblast growth factors released by wounded endothelial cells stimulate proliferation of synovial cells. AB - We demonstrated that vascular endothelial cells mechanically wounded by scraping from the substratum were able to release growth promoting factors for synovial cells as well as for endothelial cells. The wounded endothelial cell conditioned medium stimulated the proliferation of synovial cells derived from different human donors dose dependently and induced transit of growth arrested synovial cells (predominant in the G0 and G1 phases), through the S phase and into the G2 and M phases. When the wounded endothelial cell conditioned medium was applied to heparin-sepharose columns, mitogenic activity was eluted with 2.0 M NaCl. The mitogenic activity in wounded endothelial cell conditioned medium, which was heat sensitive, was inhibited by protamine sulfate and a specific mouse monoclonal antibody against basic fibroblast growth factor (bFGF). Our results are evidence that the wounded endothelial cell conditioned medium contained growth promoting factors for synovial cells, including bFGF. We also showed the presence of bFGF in the endothelial cells of the small blood vessels and stromal synovial fibroblast-like cells in patients with rheumatoid arthritis (RA). Our results suggest that the endothelial cells in the luxuriant capillaries in the synovial tissues from patients with RA may have a critical role in the stimulation of neighboring synovial cell proliferation, resulting in pronounced synovial hyperplasia. PMID- 1294744 TI - Correlates of knee pain among US adults with and without radiographic knee osteoarthritis. AB - We examined the associations of sociodemographic variables, health behaviors, health status and psychological well being with radiographic knee osteoarthritis (OA) and self-reported knee pain for 4056 US adults aged 45-74 years. Among persons with or without knee OA known correlates of radiographic knee OA (age, sex, race, obesity) were generally not associated with knee pain. Radiographic severity, psychological well being and health status were associated with knee pain, both among persons with and without radiographic knee OA, suggesting that nonradiographic correlates of self-reported knee pain are independent of whether a person has radiographic knee OA. PMID- 1294743 TI - Predictors of functional outcomes after arthroscopic partial meniscectomy. AB - OBJECTIVE: To confirm previous studies that have identified knee osteoarthritis as the principal correlate of poor outcomes after arthroscopic partial meniscectomy (APM), we considered a range of other preoperative characteristics using multivariable analyses to control for confounding variables. METHODS: One hundred five patients who had APM were studied. Selected demographic and clinical features were obtained from charts and operative notes. Preoperative and current functional status were determined by patient interviews. The principal outcomes were functional status at the time of followup, measured by the Physical Activity Scale of the SF-36 Health Status Inventory, and the Lysholm Knee Rating Scale. RESULTS: SF-36 scores improved from a mean of 53.7 to a mean of 18.2. The percentage of patients with satisfactory (> or = 77) Lysholm scores increased from 5% preoperatively to 73%. In multivariable analyses, Worker's Compensation (p = 0.003), worse baseline physical functional status (p = 0.007), and Grade III IV cartilage damage (p = 0.05) were associated with worse post-operative function. CONCLUSION: The outcome of APM is generally favorable. The extent of cartilage damage was confirmed as a correlate of poor outcome. However, Worker's Compensation and preoperative physical functional status had the greatest prognostic value and should be ascertained routinely in orthopedic outcome studies. PMID- 1294745 TI - Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal antiinflammatory drug or pure analgesic. AB - Our randomized double blinded comparison of acetaminophen versus analgesic and antiinflammatory doses of ibuprofen in the treatment of 182 subjects with knee osteoarthritis (OA) systematically evaluated soft tissue tenderness and joint swelling. Improvement in these signs of joint inflammation was associated with lessening of disability (p = 0.02), and reduction in rest pain (p = 0.07), but not with the drug treatment regimen. Thus, joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee OA. PMID- 1294746 TI - Interrater reliability of the tender point criterion for fibromyalgia. AB - The diagnosis fibromyalgia (FS) requires the existence of tender points, routinely identified by clinical examination. We evaluated the interrater reliability of digital (thumb) examination for tender points by comparison with dolorimeter examination, a procedure considered to measure accurately muscle tenderness. Subjects were 15 patients with varying rheumatological diagnoses and anatomically widespread pain. In a physician blinded procedure, 2 rheumatologists determined the tender point count by digital examination at 18 points, and the tender point threshold by dolorimeter at 12 points. A pain threshold of 4 kg/1.77 cm2 or less defined the presence of tender points under both methods. Results indicate (1) classification as FS vs other diagnosis using pain complaint and digital examination for tender points, was moderately reliable (kappa = 0.74, p < 0.005); (2) interrater agreement about presence/absence of tenderness at individual points was not significantly lowered by digital examination (kappa = 0.51, p < 0.0001) relative to dolorimetry (kappa = 0.62, p < 0.0001); however, (3) analyses on the 12 anatomical points that were common to both methods indicated that digital examination resulted in significantly more anatomical points being considered tender relative to dolorimetry. Our findings indicate that digital and dolorimeter measures are equally reliable, but have poor concurrent validity for defining tender points in FS. Implications of these findings for the classification of fibromyalgia are discussed. PMID- 1294748 TI - Liver disease, erroneously attributed to methotrexate, in a patient with rheumatoid arthritis. AB - We describe a patient with rheumatoid arthritis and Felty's syndrome who developed evidence of hepatic dysfunction initially attributed to a short course of methotrexate therapy. He was subsequently found to have nodular regenerative hyperplasia. PMID- 1294747 TI - Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection. AB - We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis. PMID- 1294749 TI - Lymphadenopathy, oligoclonal T cell receptor rearrangement and systemic lupus erythematosus. AB - To investigate the cause of generalized lymphadenopathy in case of systemic lupus erythematosus (SLE), we performed a molecular genetic analysis of lymph node, peripheral blood mononuclear cell and bone marrow specimens with T cell receptor and immunoglobulin gene probes. Oligoclonal T cell receptor rearrangements were detected in the lymph node cells. The oligoclonal T cell expansion observed is the first such example reported in SLE, and may be indicative of an immune response to specific antigenic challenge. Alternatively, these changes may represent the earliest phases of a malignant process. Molecular genetic investigations in autoimmune disease such as SLE can provide opportunities to enhance our understanding of the underlying condition, or reveal unexpected abnormalities requiring further assessment. PMID- 1294750 TI - The "shrinking lungs syndrome" in systemic lupus erythematosus--improvement with corticosteroid therapy. AB - A 35-year-old woman had a 13-year history of systemic lupus erythematosus (SLE) with recurrent flares since 1972 responding to corticosteroid therapy. In August, 1990 she presented with a 2-month history of dyspnea at rest, 4-pillow orthopnea and paroxysmal nocturnal dyspnea. Respiratory rate was 32-36/min, chest expansion 2 cm and crackles were present at the lung bases. On chest radiograph diaphragms were elevated. Pulmonary function tests (PFT) showed further reduction in lung volumes, maximum inspiratory pressures, maximum expiratory pressures and arterial blood gases. Ventilation/perfusion and gallium lung scans were normal. A diagnosis of "shrinking lungs syndrome" was made. Treatment with 40 mg of prednisone resulted in resolution of the patient's shortness of breath. PFT showed improvement in all variables. Corticosteroid therapy for acute "shrinking lungs syndrome" in active SLE can improve symptoms and pulmonary function. PMID- 1294752 TI - Simultaneous occurrence of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis in the same patient. AB - Diffuse idiopathic skeletal hyperostosis (DISH) frequently gives rise to some diagnostic confusion, as it may radiologically mimic ankylosing spondylitis (AS). A patient with features of DISH and AS is described and the literature is reviewed. The diagnostic value of sacroiliac computerized tomography is emphasized. The role of spinal mobility in the appearance of the enthesiophytes is discussed since our patient, who underwent a segmental fusion, presented different radiological features in the mobile segment and the fused region. PMID- 1294751 TI - Hypertrophic cardiomyopathy in systemic lupus erythematosus and "lupus-like" disease. Chance association? A report of 2 cases. AB - Two patients, both women, one with "lupus-like" disease, age 51 years, the other a 45-year-old with systemic lupus erythematosus (SLE), developed symptoms and echocardiographic signs of hypertrophic cardiomyopathy. One patient had a family history of sudden maternal death. Neither patient had a history of sustained hypertension and there were no significant valvular lesions detectable to account for the septal and ventricular hypertrophy. The association of SLE or any related condition with hypertrophic cardiomyopathy has not been recorded. In one patient the question of a hereditary cardiomyopathy remains a possibility. The diagnosis of the condition was based on clinical and echocardiographic grounds alone. No endomyocardial biopsies were performed. PMID- 1294753 TI - Magnetic resonance imaging assessment of sacroiliac joint involvement in Gaucher's disease. AB - A young woman with Gaucher's disease experienced acute pain in her right sacroiliac (SI) joint. Although pelvic radiographs and computed tomographic scan showed no significant change in the right SI joint, magnetic resonance imaging demonstrated an area of high signal intensity in the iliac part of the right SI joint, and a periosseous collection of blood. This skeletal location is rarely reported in Gaucher's disease; the mechanism of bone crisis is still controversial and our case suggests the occurrence of a bone infarct. PMID- 1294754 TI - Spinal cord claudication from amyloid deposition. AB - We describe the clinical course of an 81-year-old woman who was evaluated for worsening symptomatology of spinal cord claudication. Diagnostic studies revealed mild lumbar canal stenosis at L3-4, severe stenosis at L4-5 with a myelogram-CT scan demonstrating a complete block at this level mainly a result of a hypertrophied ligamentum flavum. At surgery, the ligamentum was found to be thickened and to be causing severe compression of the dural tube. Pathologic studies of the excised ligamentum flavum revealed extensive amyloid protein deposition. The amyloid was not further classified with further medical evaluation and followup failing to identify any conditions associated with local or systemic amyloidosis. PMID- 1294755 TI - Articular histoplasmosis. AB - Rheumatic manifestations of histoplasmosis are uncommon. Polyarthritis or arthralgias may occur as a part of a sensitization process in primary acute histoplasmosis. Infectious arthritis may accompany disseminated histoplasmosis or occur as solitary monoarthritis. Treatment of the latter traditionally consists of surgical excision followed by amphotericin B. Reports of clinical experience with the newer triazole compounds in treating articular histoplasmosis are lacking. We describe a patient with solitary monoarticular histoplasmosis of the knee who was successfully treated with oral fluconazole and required no surgical intervention. Specific issues that pertain to clinical presentation and management of articular histoplasmosis are discussed. PMID- 1294756 TI - Antibiotic allergy in systemic lupus erythematosus. PMID- 1294757 TI - Performance of the McMaster rheumatoid arthritis measurement questionnaire in Brazilian patients. PMID- 1294758 TI - Kikuchi's disease associated with lupus-like syndrome--a fatal case. PMID- 1294759 TI - Lymphocytotoxic antibodies in the healthy children of patients with Behcet's syndrome. PMID- 1294760 TI - Detection of localized Salmonella infection by gallium-67 citrate scan. AB - Fifteen cases (9 males, 6 females, ages: 18-73 y/o) of salmonella bacteremia were referred for a Gallium-67 citrate (Ga-67) scan to detect the focal site(s) of salmonella infection. Among them, 8 were finally proved to have focal infection(s). Their underlying diseases were systemic lupus erythematous (SLE, 4 cases), malignancies (2 cases), immunocompromise (1 case) and unknown disease (1 case). The focal infections detected were septic arthritis in 6, soft tissue abscesses in 4 and lung abscesses in 2. This report suggests that Ga-67 scan is of great value in detection of localized salmonella infection. PMID- 1294761 TI - [Kinetic studies of protein kinase A in rat liver during late sepsis]. AB - The covalent modification of receptor proteins via phosphorylation and dephosphorylation is one of the principal mechanisms controlling carbohydrate metabolism and is known to be regulated by various protein kinases. Recent studies indicated that many hormones may exert their effects on cellular metabolism by regulating intracellular c-AMP levels and by activating a c-AMP dependent protein kinase, i.e., protein kinase A. The metabolic disturbances during sepsis are characterized by an initial hyperglycemia followed by a progressive hypoglycemia and a depletion of hepatic glycogen content. The latter is coupled with a slowdown in glycogenesis, an accelerated glycogenolysis, and a depression in gluconeogenesis in the liver. Since the liver is the major organ that regulates the homeostatic level of blood glucose, it is conceivable that the sepsis-induced glucose dyshomeostasis might be mediated by changes in protein kinase activity and the kinetic characteristics of enzymes. The present experiment was designed to study the correlation between protein kinase A and the pathophysiology of hepatic glucose dyshomeostasis during sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP). Late sepsis occurred 18 hours after CLP. Protein kinase A was extracted from the rat livers by acid precipitation and ammonium sulfate fractionation, and then partially purified by DEAE-cellulose. The results show that in the late sepsis, type-I protein kinase A (eluted at low ionic strength) activity was significantly decreased by 34-52% (P < 0.01). The kinetic parameters such as Vmax's for ATP, histone, and c-AMP were also significantly decreased from the control values of 6.1 +/- 0.9, 5.4 +/- 0.8, and 5.1 +/- 1.9 nmoles/mg.min. to 3.6 +/- 0.5, 2.8 +/- 0.3, and 2.5 +/- 0.5 nmoles/mg.min., respectively. Analysis using Hill's equation indicates that the S0.5 and n (Hill coefficient) values of the various substrates and activators for type-I protein kinase A remained unchanged. In the case of type-II protein kinase A (eluted at high ionic strength), the Vmax, S0.5, and n values for ATP, histone, and c-AMP were unchanged during late sepsis. The results of the present study indicate that the activities and kinetic characteristics of type I protein kinase A in rat liver are modified during late sepsis. Since protein kinase A is known to regulate glucose metabolism through adrenergic receptor mediation, these findings may have a pathophysiological significance in the understanding of hepatic glucose dyshomeostasis during sepsis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1294762 TI - [Phagocytosis of the reticuloendothelial system in diabetes mellitus]. AB - It has been assumed that patients with diabetes mellitus (DM), who are usually susceptible to bacterial infections, have a depression of the antibacterial defense mechanism. This study was undertaken to substantiate the hypothesis that phagocytosis of the reticuloendothelial system (RES) is depressed in diabetic patients. It is believed that intravenously injected colloidal suspensions whose particles are unable to pass through the capillary barrier will be phagocytized mainly by the reticuloendothelial cells in the liver and spleen. In the present study, the RES phagocytic index (RESPI) was measured in 48 subjects: 20 normal controls and 28 patients with DM. Measurements were based on the rate of disappearance (T1/2) of radioactivity in the heart (blood pooling) after rapid I.V. injection of 3mCi of Tc-99m phytate (2mg phytate). Using a gamma camera, sequential images of the liver and heart were obtained, and computer-generated time-activity curves were established. The T1/2 was then calculated. Our results revealed that the RESPI values in the DM group were significantly increased as compared to the normal control group (normal control = 4.60 +/- 1.01; DM = 6.78 +/- 3.83; P < 0.05). This prolonged half-disappearance time of blood radioactivity in diabetic patients is interpreted as a reflection of impaired phagocytotic efficiency in the reticuloendothelial system. The results of this preliminary study add support to the in vivo evidence explaining the increased susceptibility to infection in diabetic patients. PMID- 1294763 TI - [A study of the satisfaction of clients with the home visiting service provided by public health nurses]. AB - The purpose of this study is to explore the satisfaction of clients with the home visiting services provided by public health nurses. In addition, the related factors that influence this satisfaction are to be explored. A structured questionnaire was used for data collection. This study comprises 247 subjects who were chosen via distributive sampling, 222 questionnaires were completed for use. The completed percentage achieved 90%. Factors analysis was used to discern the satisfaction components. The contents of the client's satisfaction can be broken down into 5 major areas: (1) the assistance provided by home health services; (2) the professional capacities of the home-visiting nurses; (3) the disturbance caused by the home health services; (4) the home visiting nurses' capacity for instruction and reaction; (5) the autonomy of home health services. The results of this study indicate that the clients' satisfaction ratio achieves 89%. A stepwise multiple regression was used to analyze the related factors that influence the clients' satisfaction. We found that the most important variables were "the assistance provided by home-visiting services", "the necessity of home visiting services", and "the variation in client diagnosis". The predictable variance of these three variables reaches 34.8%. PMID- 1294764 TI - Pneumatosis cystoides intestinalis arising in jejunal diverticular disease: report of a case and a suggestion to its pathogenesis. AB - The occurrence of pneumatosis cystoides intestinalis (PCI) in the gastrointestinal tract is rare. Among the cases already documented in the English language literature, the association of PCI with jejunal diverticulosis has only been mentioned once or twice. We herein report a case of a 63-year-old woman who had both entities concurrently in a segment of the jejunum. What is important to note is the relationship of PCI to the diverticulosis and its possible pathogenesis. Through histological examination and review of related articles, we are convinced that a mechanical theory plays a pivotal role when both diseases occur in the same segment of intestine and are compounded by obstruction or impaired peristalsis. This finding, when properly applied to PCI in other settings, helps to resolve the pathogenesis of PCI and other related gas-filled cysts. PMID- 1294765 TI - Osler-Weber-Rendu disease: a six generation family. AB - A Taiwanese family, with at least nine members in six generations has been affected with Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia. It is an autosomal dominant familial disease which involves systemic subepithelial fibrovascular dysplasia and manifests with telangiectasia or angiomas of the face, the palms, or the mucosa of the aerodigestive tract (such as the nose, lips, oral cavity, or stomach, etc.). The most common clinical symptom is recurrent epistaxis with/without upper gastrointestinal bleeding which may be resistant to the otolaryngologist's best efforts for control. Repeated bleeding marks the typical course of the disease. Epistaxis from hereditary hemorrhagic telangiectasias often requires a combination of therapeutic approaches. Carbon dioxide laser surgery was highly successful in decreasing postoperative morbidity and epistaxis in the four patients we treated. PMID- 1294766 TI - Internal jugular phlebectasia. AB - Phlebectasia, defined as abnormal venous dilation, may occur in a number of different sites. Two cases with definite diagnosis of internal jugular phlebectasia were reported. The first case was a 6-year-old girl with a bulging mass on right neck for 3 years. Angiography and CT scan showed definite diagnosis, and the bulging mass was resected from the internal jugular vein (IJV). The second case was a 66-year-old female patient, also complained of a bulging mass on her right neck. Sonogram and CT scan also showed the same diagnosis. Because it did not bother the patient, she was just under close observation. From the three kinds of diagnostic modalities, we found sonography is an effective technique because of its clarity, safety and low cost. PMID- 1294767 TI - [Neurogenic pulmonary edema: five cases report]. AB - Five patients with neurogenic pulmonary edema (NPE) were reported. The edemas were caused by head injuries in four patients and by a craniotomy in the fifth. The onset of NPE was either acute (3 hours after injury) or was slow to develop (4 days later). Clinical symptoms included the sudden onset of coughing, tachypnea, tachycardia, and pink bubbly sputum. Moreover, the patients also suffered cyanosis, confusion, or respiratory failure. The distribution of the resulting pulmonary edema was diffuse in 4 cases and localized within a single lobe of the lung in 1 case. Treatment of the NPE included reducing intracranial pressure (glycerol), diuresis (furosemide and mannitol), narcotics (morphine, phenobarbital), and blocking the peripheral effect of sympathetic reflex activity (hydralazine, sodium nitroprusside). Mechanical ventilation support (CPU-1) in combination with controlled hyperventilation may also be necessary. The inability to correct hypoxemia without toxic levels of oxygen necessitates the use of PEEP (positive end-expiratory pressure, +5-10 cmH2O). Resolution of symptoms was noted 24 to 48 hours after treatment in 4 patients. Early diagnosis and intensive care of the pulmonary edema may have a significant bearing on the recovery of lung functions. Unfortunately, 4 of the patients failed to survive because of central nervous system failure. We therefore want to emphasize that NPE can cause secondary deterioration of neurological functions. In conclusion, when dealing with respiratory distress patients with CNS injuries, the possibility of additional damage from a NPE must be taken into consideration. PMID- 1294768 TI - [Clinicopathological study on progressive hereditary nephritis: observations of ultrastructural lesions in the glomerular basement membrane]. AB - Four boys and six girls with progressive hereditary nephritis were studied clinicopathologically. Renal biopsy was performed 16 times in ten cases. Mean age at renal biopsy was 7.3 years old (range 2 to 14 years old). The obtained results were as follows: (1) Montages of electron micrographs were prepared to complete one whole glomerulus. The length of the glomerular basement membrane (GBM) with the characteristic splitting of the lamina densa (Reticulation) was measured and expressed as a percentage of the total length of the GBM. The range of the percentage of the GBM with Reticulation was from 2 to 43% (13.4 +/- 10.0%, mean +/- SD, n = 16). In 4 cases of the 5 cases performed serial renal biopsy, the percentage of the GBM with Reticulation at the 2nd biopsy increased compared with the 1st one. (2) Protein excretion in the urine, serum albumin, alpha 2-globulin, fibrinogen and total cholesterol showed the correlation with the percentage of the GBM with Reticulation. (3) Incomplete ruptures (deep invasion of the epithelial cells into the thickened GBM with Reticulation) were observed. Those suggested that the GBM became fragile associated with the expansion of Reticulation and finally ruptured. Gaps of the GBM were observed 0 to 3 per in one glomerulus (0 to 1.87 per 1mm GBM) and the serial biopsies showed an increase in the number of the gaps as time passed. (4) This study showed the increase in factors activating the blood coagulation such as total cholesterol and fibrinogen, with the expansion of the GBM with Reticulation. And in a nephrotic case, fibrin strands were observed in the glomerular capillary loops and in the GBM. These findings suggest that the activation of the blood coagulation plays a role for the damage of the glomeruli in progressive hereditary nephritis. PMID- 1294769 TI - [Echocardiographic assessment of cardiac function in the children of chronic renal failure with cardiomegary]. AB - Five children (four boys and one girl) with chronic renal failure (CRF) developed congestive heart failure 0.5 to 11 years after the onset of the disease. Their ages were from 4 to 13 years old. They noticed tachypnea, tachycardia, cough, chest anxiety, general fatigue and their chest X-rays showed cardiomegaly with cardio-thoracic ratio (CTR) of from 55 to 63% and pulmonary congestion. Their echocardiograms showed no cardiomuscular hypertrophy, but the dilatation of left ventricular diastolic diameter (LVDd), and the decreased ejection fraction (EF) were observed. They were treated with water restriction, antihypertensive agents, cardiotonics and dialysis. Their clinical symptoms improved promptly, but their cardiomegary and echocardiographic findings improved gradually. The causes of heart failure in these patients seemed to be due to uremia, fluid overload and hypertension. The echocardiographic examination was useful for the management of the children with CRF in heart failure. PMID- 1294770 TI - [Clinical effects of six-month short time biofiltration]. AB - The clinical effects of six-month short time biofiltration (SBF) were evaluated using a B-A-B' study (B, B': conventional bicarbonate hemodialysis; CBHD, A:SBF) in ten patients maintained on CBHD three times a week. An F80 hemodiafilter (1.9 m2, polysulfone, Fresenius) was used. In addition to routine clinical parameters for a patient on regular dialysis treatment, plasma von Willebrand factor antigen (vWF) (an index of stimulation of vascular endothelium), and the methylguanidine/creatinine ratio (MG/Cr) and malondialdehide (MDA) (indices of the levels of oxygen radicals), were evaluated. Nine patients completed the study, one patient dropping out at the 12th week of A because of muscle cramps during SBF. The treatment time was 2 hours in six cases and 2.5 hours in three cases. The mean blood flow rate was 280 +/- 42 (SD) minutes. Using the urea kinetics model, the mean KT/V was 1.26 +/- 0.28, and the mean protein catabolic rate was 1.22 +/- 0.18 g/kg body weight/day at the end of A. No change in ultrafiltration, blood pressure, cardiac function (assessed by echocardiography), CTR, human atrial natriuretic peptide, total protein, albumin, uric acid, serum creatinine, sodium, calcium, inorganic phosphorus, vWF, or MDA was found between each period. Blood urea nitrogen, c-PTH, and MG/Cr increased during the A period. Serum magnesium and beta-2 microglobulin decreased during the A period. Blood gas results, on the whole, did not change. In a patients, however, acidosis gradually developed. An increase in substitution fluid from 5 L/session to 7.5 L/session improved the acid-base balance in that patient. In conclusion, SBF is as effective as CBHD in removing small molecules and maintaining cardiocirculatory status, and is superior to CBHD in removing beta 2-microglobulin and is less stimulative to the endothelium than CBHD. PMID- 1294771 TI - [Effect of weight loss on the reduction of blood pressure in obesity hypertension -hyperinsulinemia and renal sodium retention]. AB - The role of insulin and dopamine on blood pressure and renal sodium excretion was evaluated in 10 obese hypertensive patients. Essential hypertensive subjects (age 49.7 +/- 7.7) with at least 26.0kg/m2 obesity were hospitalized and a 2000k cal diet for 7 days (control periods) followed by a 800 k cal for 21 days were given. Salt intake was maintained at 10 g/day throughout this study. Mean blood pressure (MBP), plasma insulin (IRI), urinary dopamine and fractional excretion of sodium (FENa) were measured in both diet periods. Body mass index significantly decreased from 31.6 +/- 4.6kg/m2 to 28.6 +/- 4.1 kg/m2 after weight reduction (P < 0.001). MBP significantly lowered from 112.8 +/- 14.1 mmHg to 100.4 +/- 12.4 mmHg (P < 0.01) and IRI from 9.11 +/- 5.0 microU/ml to 6.3 +/- 5.5 microU/ml (P < 0.001) after weight loss. We observed a significant correlationship between delta MBP and delta IRI (r = 0.754, P < 0.01). Also, we observed a significant correlationship between delta MBP and delta FENa (r = -0.835, P < 0.01). A significant relationship was observed between urinary excretion of sodium and urinary excretion of dopamine (r = 0.507, P < 0.05). We concluded that sodium retention and increase of sympathetic nervous activity by hyperinsulinemia might play an important role of hypertension, and blood pressure reduction by weight loss resulted from decreased insulin and increased excretion of sodium in obesity hypertension. PMID- 1294772 TI - [A diabetic patient with empty sella syndrome accompanied by stimulated guanidinoacetic acid metabolism]. AB - Since urinary guanidinoacetic acid (GAA) derives from the kidneys, its detection is suggested to be associated with renal disease. We have been making a practice of investigating renal GAA production in diabetic patients, using a citrulline/creatine loading test. We noted a marked increase in urinary GAA excretion in 1 patient. Since GAA-synthesis is hormonally regulated, we made a through investigation of endocrine function in this patient. She was a 58-year old woman with a 15-year history of diabetes mellitus, proliferative diabetic retinopathy, and negative microalbuminuria. There was a high plasma GH level and urinary 17-KS analysis revealed an increase in the adrenal androgen-derived fractions. Based on the X-ray finding of ballooning of the sella turcica and the MRI data, empty sella syndrome was diagnosed. It was suggested that stimulated anabolic hormone release had accelerated renal nitrogen metabolism and induced aggravation of her retinopathy. The findings in this patient implied the involvement of hormones in the development of diabetic complications. PMID- 1294773 TI - [A case of Bufferin induced acute interstitial nephritis--analysis of immune cells and cytokine]. AB - This paper describes a case report of acute interstitial nephritis associated with Bufferin. A 15-year-old girl were referred to our hospital due to fever and renal dysfunction. Laboratory findings showed elevation of serum BUN and creatinine, and increased urinary beta 2-MG excreation. Light microscopic findings of her renal biopsy specimen revealed edema and numerous inflammatory cells in the interstitium, and minor alterations in glomeruli. The interstitial infiltrates consisted mainly of T cells and also monocytes/macrophages. Interstitial cells were labelled with antibodies to interleukin (IL)-1 and tumor necrose factor (TNF). Bufferin was positive by lymphocyte stimulation test. Thus, we considered that this drug was causative in this case. This observation suggests the participation of cell-mediated immune injury in drug induced acute interstitial nephritis. PMID- 1294774 TI - [Effects of growth factors on proliferation of cultured human peritoneal mesothelial cells]. AB - Loss of ultrafiltration during continuous ambulatory peritoneal dialysis (CAPD) is often caused by the structural peritoneal membrane alteration, namely the disappearance of mesothelial cells and the proliferation of peritoneal collagen fibers. The interleukin hypothesis has been proposed to explain the etiology of peritoneal fibrosis. The CAPD procedure has been shown to induce macrophages and lymphocytes in the peritoneum, resulting in the production of interleukin-1 (IL 1) and interferon-gamma (IFN-gamma), which may be promote to the development of peritoneal fibrosis. On the other hand, the mesothelial defect can be rapidly restored by proliferation of mesothelial cells implanted on the wound surface. In this study, we demonstrated that IL-1 beta, IFN-gamma, epidermal growth factor (EGF) and platelet derived growth factor (PDGF) enhance to the growth of cultured human peritoneal mesothelial (CHPM) cells. The cell cultures were derived from surgically removed omentum using the enzymatic disaggregation method. CHPM cells were cultured with Ham's F-12 medium containing 10% FCS up to third generation. At a concentration of 1x10(4) cells/well were cultured with various concentrations of IL-1 beta, IFN-gamma, EGF, PDGF and IL-6. [3H] TdR (37MBq/well) was added to the cultures during the last 12hr of the 48hr culture period and then radioactivity was measured to determine the uptake of [3H] TdR. It was shown that IL-1 beta, IFN-gamma, EGF and PDGF induced the proliferation of CHPM cells in a dose dependent manner when cultured in medium containing 3% FCS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294775 TI - [Studies of the analysis of urinary proteins from children with renal diseases by reversed-phase high performance liquid chromatography]. AB - In order to analyze urinary proteins from patients with various renal diseases, a reversed-phase high performance liquid chromatography (HPLC) with IPG PACK ODS column packed with polyporous glass was used. The reproducibility of standard proteins was good. The results by this method correlated well with those by radioimmunoassay or laser nephelometry, precolumn procedure needed the centrifugation only. The reversed-phase HPLC was superior to the other HPLC methods in the analysis of urinary proteins for its simplicity and high sensitivity. The peaks of both alpha 1-acid glycoprotein (alpha 1-AGP) and human serum albumin (HSA) in the chromatogram was regarded as the marker of renal damage. Urinary alpha 1-AGP/HSA ratio was calculated after measuring these two peak areas. As a result, it was significantly higher in the urine from patients with various glomerulonephritis (GN) than in those from healthy children. In the patients with postural proteinuria, it was the same level as that in healthy children. These date suggest that the urinary alpha 1-AGP/HSA ratio would be a beneficial indicator to find out the patients with GN from among children with proteinuria. Furthermore, it seems that this method is suitable for use in routine screening of renal diseases for its simplicity and speed. PMID- 1294776 TI - [The production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with non-insulin dependent diabetes mellitus]. AB - The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with PMA, FMLP, aggregated IgG and phagocytosis were determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). The H2O2 production of PMN after the stimulation was measured using by flow cytometry. The patients were divided into four stages as follows: (1) non-microalbuminuric stage, (2) microalbuminuric stage, (3) proteinuric stage without impairment of renal function (less than 1.2 mg/dl of serum creatinine) and (4) proteinuric stage with impairment of renal function (more than 1.3mg/dl of serum creatinine). The H2O2 production after stimulation with PMA or phagocytosis was significantly higher in patients with NIDDM than normal controls. And also, there is the tendency of an increase in the H2O2 production after stimulation with FMLP or aggregated IgG. This increase of the H2O2 production was observed in all four stages of NIDDM patients after the stimulation, especially in patients with renal failure associated with diabetic nephropathy. These results suggest that reactive oxygen species produced by PMN after stimulation under various conditions may play an important role in the progression and exacerbation of diabetic nephropathy. PMID- 1294777 TI - [A case of acute interstitial nephritis and nonoliguria acute renal failure induced by cimetidine]. AB - Cimetidine is a histamine H2-receptor antagonist. Widely it is prescribed, and then various side effects have been increasingly recognized. Acute renal failure as a result of acute interstitial nephritis is one of the most important adverse effect. We report a case of biopsy-proven acute interstitial nephritis following cimetidine therapy. Farther more, we review other reported cases of cimetidine induced acute interstitial nephritis, and discuss the clinical features and a role of immunological mechanisms of these cimetidine-induced disorders. A 52-year old woman was admitted because of fever and protenuria. A month before admission, she developed gastric ulcer and was given cimetidine 600mg orally a day by a near physician. Laboratory data on admission included the following: white blood cell count, 14700/microliters; eosinophils, 6%; BUN, 50.7mg/dl; Cr, 7.6mg/dl; CRP, 34.0mg/dl. All drugs were discontinued because we suspected drug-induced acute renal failure, especially by cimetidine. Renal biopsy performed on day 3 showed interstitial nephritis with lymphocyte infiltration which was composed mainly of T cell. T4/T8 ratio was determined to be 1. There was neither predominance of helper nor cytotoxic cells in T cell subpopulation. We reviewed 22 cases reported and discussed the features of cimetidine-induced interstitial nephritis. The most important thing is to monitor renal function periodically with the suspicion of this disorder. On the detection of abnormality of laboratory data, cimetidine should be discontinued. PMID- 1294778 TI - [A successfully treated case of acute renal failure due to acute immune hemolytic anemia and nontraumatic rhabdomyolysis induced by streptomycin reinjection]. AB - A case of acute immune hemolytic anemia associated with non-traumatic rhabdomyolysis (NTR) induced by streptomycin (SM) reinjection, which developed acute renal failure, has been reported. A 70-year-old female was admitted to our hospital because of sudden macroscopic hematuria after reinjection of 1g. SM. Laboratory findings on admission were as follows; hemoglobin and myoglobin were positive in urine. RBC 129 x 10(4)/microliters, Hb 4.9g/dl, Ht 11.1%, reticulocytes 52/1000, serum indirect billirubin 3.8g/dl, LDH 9, 230 WU, BUN 149mg/dl, Cr 7.9mg/dl, myoglobin 1, 400ng/ml and haptoglobin 10.6mg/dl. The drug lymphocyte stimulating test of SM was positive (215%). A direct antiglobulin test was also positive. An indirect antiglobulin test was negative, but became positive after incubation with SM. These observations made the diagnosis of SM induced hemolytic anemia associated with NTR. On the second hospital day she developed anuria, and was put on hemodialysis treatment. Two months after the acute hemolytic episode and acute renal failure she recovered and is presently in good health without recurrence. PMID- 1294779 TI - [Tuberculosis in young generation: a report from six general hospitals]. AB - We investigated epidemiologic and clinical aspects of tuberculosis in young generation and pointed out problems in ambulatory treatment. In six general hospitals in Tokyo, 418 cases of tuberculosis (285 males and 133 females) were diagnosed between 1983 and 1991. They were divided into three groups; 1) young group, 10 to 29 yr (62 cases), 2) middle age group, 30 to 69 yr (255 cases), 3) elderly group, above 70 yr (101 cases). And the risk of clinical breakdown, method of case finding, radiological findings, extra-pulmonary lesions, method of diagnosis, relationship with epidemics, patient's delay, doctor's delay, drug regimens and patient's compliance in each group were investigated. In addition, after completion of therapy we sent them survey questions about relapse and attack of tuberculosis among their families. Results were followings. 1) Estimated risk of clinical breakdown by age was calculated as follows, (the number of patients)/(the population of Tokyo)/(estimated incidence of infection). This was extremely high in young group. 2) Sixteen percent of patients in young group were related with epidemics and another eight percent with familial outbreaks. 3) Although many patients in young group showed focal lesions in chest radiographies, the rate of symptomatic patients was 61% and that was almost same as in other groups. 4) The rate of patients showing atypical radiographic findings, extra-thoracic lymphadenopathy and idiopathic pleuritis were relatively high in young and elderly group. 5) Results of survey questions showed no relapse among ambulatory treated patients. Familial outbreaks (three cases) were thought to be caused by long patient's delay and not by ambulatory treatment of smear positive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294780 TI - [Case study of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 production peripheral blood monocytes in patients with diabetes mellitus complicated by pulmonary tuberculosis]. AB - Patients with diabetes mellitus (DM) show an increased susceptibility to bacterial infections due to the presence of neutrophil dysfunction. Susceptibility to tuberculosis has also been reported in such patients, however, the reason remains unclear. This study measured the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL 6) by the peripheral monocytes of patients diagnosed with pulmonary tuberculosis accompanied by DM (TB+DM) and patients without DM complications (TB) using age matched, healthy control subjects for comparison. Also examined was the relationship between cytokine production and DM control. The results were as follows: (1) The production of IL-1 beta, TNF alpha and IL-6 in TB patients was significantly higher than that observed in the healthy control subjects. (2) The production of IL-1 beta, TNF alpha and IL-6 in TB+DM patients was significantly lower than that observed in the TB patients. (3) The production of IL-1 beta and TNF alpha in TB+DM patients with poor control was significantly lower than that observed in the patients with good control. (4) The TNF alpha production had a significant inverse correlation to HbA1c in the TB+DM patients. This study demonstrated that the production of cytokines is impaired in TB+DM patients and suggests a close correlation between tuberculosis immunity and DM. PMID- 1294781 TI - [Three cases of young adults advanced pulmonary tuberculosis due to patient's and doctor's delay]. AB - Three young adults advanced pulmonary tuberculosis due to delay of therapy were reported. In case 1 and 3, their delays resulted from difficulty in diagnosis, in case 2, from neglecting medical counseling. Each cases revealed bilateral diffuse shadows on chest roentgenograms on admission, which were typical shadows of advanced pulmonary tuberculosis. Malnutrition might contribute to the development of the diseases, which were improved by anti-tuberculosis therapy and hyperalimentation therapy. These cases were suggested some clinical problems characteristic of pulmonary tuberculosis of young adults. PMID- 1294782 TI - [Diagnostic role of fiberoptic bronchoscopy for mycobacterial diseases]. AB - From 1981 to 1991, 5,572 patients underwent bronchoscopic examination, in this series 3,754 patient's samples were sent for determination of mycobacterial isolation. In the 506 samples, mycobacterial bacilli were detected with smear or culture. In the low tuberculous incidence area like northern part of America, many reporters supported the opinion that routine bronchial aspirate detection for tuberculosis was not cost-effective. Inversely, in the high tuberculous incidence area like Hong Kong, M. lp et al. claimed the usefulness of routine bronchial aspirate examination for mycobacterial bacilli. Japan was regarded as moderate tuberculous incidence area. We review a ten-year experience with fiberoptic bronchoscopy for mycobacterial isolation. Our results suggest that in an area with a moderate prevalence of tuberculosis, bronchoscopic examination for mycobacterial disease is useful in the selected hospitals for the selected cases. In Japan, the smear positive prevalence has been on the increase from 1982. We estimate that the Japanese popularization of fiberoptic bronchoscopy may influence a part of the Japanese epidemic statistical analysis of mycobacteriosis. PMID- 1294783 TI - [Diagnostic role of fiberoptic bronchoscopy for mycobacterial diseases- serological diagnosis]. AB - Detection of IgG antibodies against purified cord factor (trehalose-6, 6' dimycolate) prepared from Mycobacterium tuberculosis H37Rv was carried out by the method of enzyme-linked immunosorbent assay (ELISA) and its diagnostic usefulness was also evaluated in this study. Sera from 65 patients with active pulmonary tuberculosis, 58 patients with inactive pulmonary tuberculosis, 36 patients with diseases other than tuberculosis and 66 healthy adults were examined. Patients with active pulmonary tuberculosis showed significantly higher titers of IgG antibodies against cord factor than other groups (p < 0.001). Patients with inactive pulmonary tuberculosis also showed significantly higher titers of IgG antibodies against cord factor than patients with diseases other than tuberculosis and healthy adults (p < 0.001). An antibody titers of greater than 0.29 were established as a positive ELISA test. For patients with active pulmonary tuberculosis, the ELISA had a sensitivity of 85% and a specificity of 96%. From these results, it is concluded that the detection of IgG antibodies against cord factor is useful for the serodiagnosis of active or inactive pulmonary tuberculosis. PMID- 1294784 TI - [Comparison of MB-Check, BACTEC, and egg-based media for recovery of mycobacteria]. AB - The rate of recovery and time to the detection of mycobacteria from clinical specimens were measured for biphasic and radiometric liquid-based culture systems and egg-based media (3% Ogawa and Ogawa K). From the 245 sputum specimens processed, a total of 86 (35.1%) mycobacterial isolates were detected. Of these, 81 (94.2%) and 80 (93.0%) isolates were detected with the MB-Check and BACTEC systems, respectively, and 65 (75.6%) isolates were detected with the 3% Ogawa egg method. The difference in the percentages of positive cultures between the two systems based on liquid media and the 3% Ogawa egg method was significant (P < 0.01). This difference was even greater among smear-negative specimens. The detection time was shorter with the liquid-based systems. The mean times to the detection of the Mycobacterium tuberculosis complex were 19.1 days with the MB Check system, 13.4 days with the BACTEC system, and 21.7 days with the 3% Ogawa egg method. These results indicate that both the MB-Check and the BACTEC systems, based on liquid media, are efficient for the recovery of mycobacteria. PMID- 1294785 TI - [Polymerase chain reaction for identification of Mycobacterium in sputa]. AB - Polymerase chain reaction was applied to the diagnosis of mycobacterial infections. This reaction could detect bacteria in clinical specimens within a few hours. Sensitivities of the five primer systems reported in 1990 were compared. It was proved that the primer system reported by Eisenach et al. was as sensitive as culture on Ogawa's medium for the detection of Mycobacterium tuberculosis in sputa. Other systems were found to be less sensitive than this system, and the nested PCR should be applied to make these systems highly sensitive. For the practical application of PCR method, we should improve the detection system to fit for the practice in clinical laboratory. High cost of PCR system could be another barrier for the practical application. PMID- 1294786 TI - [DNA probe and polymerase chain reaction for detection and identification of mycobacteria]. AB - The DNA probe and polymerase chain reaction (PCR) technique for detection and identification of mycobacteria were compared with the conventional smear and culture method. The results of identification by DNA probe agreed well with those of the biochemical method. Moreover, six percent of Mycobacterium avium complex (MAC) were revealed to be mycobacteria other than MAC by DNA probe. The nested PCR for detection of gene coding protein antigen b of Mycobacterium tuberculosis complex showed excellent specificity and sensitivity. Then we applied this technique to rapid detection of M. tuberculosis in 222 clinical samples. The agreement between nested PCR and the biochemical method was excellent, and 17 cases were diagnosed by only nested PCR in spite of negative results by smear and culture. These cases were unlikely to have yielded false positive results since their clinical features were compatible to tuberculosis. From these data, it was considered that the DNA probe and PCR technique were extremely useful strategies and would contribute to rapid diagnosis of mycobacterial infectious diseases. PMID- 1294787 TI - [Rapid genetic identification system of mycobacteria]. AB - Rapid colorimetric hybridization method was applied for the identification of mycobacteria and phylogenetic detection and identification system of mycobacteria of polymerase chain reaction method was designed. Quantitative DNA-DNA hybridization in microdilution plate was used to identify 22 mycobacterial species. This method could identify 90% (178 among 194 trials) of clinical isolates within 3 hr. Ten percent of clinical isolates did not belong to any of the established 22 species. Through this work, we found Mycobacterium abscessus is genetically independent from M. chelonae and proposed M. abscessus as a distinct species. M. pregrinum had been classified as M. fortuitum, however, it was also found as a independent species. Thus the name M. peregrinum was officially revived and acquired the taxonomic position. Highly sensitive genetic detection system of mycobacteria was designed by using polymerase chain reaction (PCR) method. Common mycobacterial sequence of 16S ribosomal RNA gene was first amplified by a single pair of PCR primers from staining negative sputum and the amplified DNA was identified by species specific DNA probe because the amplified fragment contained species specific sequence. PMID- 1294788 TI - [An esophageal foreign body in a child causing the development of an esophago pericardial fistula and suppurative pericarditis]. PMID- 1294789 TI - [The juridical aspects of surgical activities]. PMID- 1294790 TI - [The treatment of intestinal invagination in children]. AB - The work discusses the results of analysis of clinical diagnostics of intestinal intussusception in 197 children and their treatment. Age peculiarities of the clinical course of intussusception were revealed. The characteristic pathomorphological changes of the walls of the invaginated portion of the intestine were studied according to the duration of the disease and the type of intussusception. The causes of the inefficacy of nonoperative correction of the invagination are identified. The tactics of intussusception management and the indications for operative treatment were elaborated on the basis of these data. The author suggests his own method for desinvagination. Operations were conducted on 62 children. Nonoperative treatment by the method developed by the clinic was applied in 169 (85.7%) children, the invaginated portion was reduced in 139 (82.2%) children and the treatment proved ineffective in 30 (17.8%) children. The author recommends the method for reduction developed at the clinic as the method of choice in the management of intestinal intussusception in children. PMID- 1294791 TI - [The concept of iatrogenic diseases]. PMID- 1294792 TI - [The diagnosis of motor disorders of the small intestine in peritonitis in children and the rationale for pathogenetic methods of correction]. AB - The work deals with the results of experimental (200 animals) and clinical (20 patients) study into the role of the efferent link of the autonomic nervous system in regulating motor activity of the small intestine and the possibility of using direct electroenteromyography in the diagnosis of the stages of paresis and the degree of motor disorders in peritonitis. The pathogenetic methods of treatment of intestinal paresis are substantiated. Medicamentous stimulation of the cholinergic nervous system in peritonitis is effective only when intactness of the intramural ganglia is maintained, in which case the electroenteromyographic test with neostigmine methylsulfate or cerucal may be conducted. The pathogenetic method of treatment in all other cases is medicamentous blockade of the adrenergic nervous system. PMID- 1294793 TI - [Fecal incontinence in Hirschsprung's disease in children]. AB - Among the criteria of evaluation of the results of operative treatment of Hirschsprung's disease in children, along with the absence of constipation is the function of defecation control. The authors examined 27 patients with fecal incontinence after Duhamel's operation. It was established that fecal incontinence in children after operative treatment of Hirschsprung's disease may be caused not only by affection of the external sphincter muscle of the anus, the nerve plexuses, and adaptation of the rectum to the new conditions after the pull through operation, but also by trauma inflicted to the levator ani muscle. In children with severe damage to the levator group of muscles consequent upon operative treatment of Hirschsprung's disease, operative intervention for creating the anorectal angle is indicated. PMID- 1294794 TI - [The late examination results in children with pylorospasm and dyskinesia of the proximal sections of the small intestine]. AB - The article analyses the late-term results of examination of 46 children with neurogenous dyskinesias of the gastrointestinal tract which were recognised in infancy for the first time. The author believes that the functional, motor evacuation, and sphincter disorders of the proximal parts of the digestive tube lead to the development of organic noninfectious diseases of the gastroduodenal system. PMID- 1294795 TI - [Changes in the respiratory coefficient during the intravenous administration of energy substrates in the early postoperative period in children]. AB - Changes of the respiratory coefficient in the early period after operation on the abdominal organs were studied in 18 children during intravenous infusion of the main energy-producing substrates glucose and fat for 60 minutes. Their doses were in proportion to the age daily requirements and constant for each child during the whole period of study. The mean respiratory coefficient before infusion of the substrates was 0.84 +/- 0.005 on the first postoperative day, 0.857 +/- 0.009 on the second, and increased further to 0.888 +/- 0.008 and 0.909 +/- 0.023 on the third and fourth days, respectively. During infusion of energy-producing substrates the mean value of the respiratory coefficient reduced significantly (p < 0.001). It was 0.702 +/- 0.005 on the 60 th minute of the first day, 0.726 +/- 0.004 on the second day, and then increased to 0.761 +/- 0.009 and 0.778 +/- 0.01 on the third and fifth days, respectively. Before infusion of the substrates, the relative amounts of energy produced due to oxidation of fast and glucose were, respectively. 54.6% and 45.4% on the first day after operation. Later the share of fat decreased and that of glucose increased to 31.1% and 68.9%, respectively by the fifth day. During infusion of the substrates the relative amount of energy obtained at the expense of fat grew to 100% on the 60th minute of the first day and was 93.5% on the second day, the amount of glucose was 6.5%. The respective figures were 81.6% and 18.4% on the third day and 75.8% and 24.2% on the fifth day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294796 TI - [Computed tomography of the pelvis in pediatric proctology]. AB - The article shows the wide possibilities of computed tomography (CT) diagnosis of the topography of muscles forming the external sphincter of the anus (ESA) in patients with developmental anorectal anomalies and in trauma and rupture of the perineum. It is shown that in anorectal anomalies with fistulas opening into the urinary system the puborectal muscular sling is "drawn up" ventrally in relation to the external sphincter elements lying closer to the surface. Analysis of the results of CT examination of the pelvic floor in 16 children with anorectal anomalies showed that the degree of development of the sphincter muscles does not always correspond to the level of atresia. For instance, the mass of the ESA muscles is manifested more in some forms of cloacal atresia than in "tubular" stenoses of the rectum (anorectal stenosis--Curravino-triad component) (G. Curravino, 1981). CT examination of children with this complex of caudal anomalies allowed the authors to reveal a fourth constant component: dysplasia of the pelvic floor and a specific developmental anomaly of the anal sphincter. CT is the method of choice in the examination of children with this pathological condition because it makes it possible to recognise the presence of presacral masses. The use of CT in traumas and ruptures of the perineum allows the depth and extension of ruptures of the ESA muscles to be authentically determined. PMID- 1294798 TI - [The clinical significance of membrane-destructive processes and their correction in children with suppurative surgical infection]. AB - The results of examination of 101 patients with purulent surgical infection provide evidence of considerable disorders of cell membrane metabolism which correspond to the severity of the disease. Three states of the antioxidant defence system were distinguished: compensated, subcompensated, and decompensated. It is suggested that antioxidant and membrane-stimulating treatment should be applied with consideration for the types of the course followed by the metabolic processes (metabolically latent, lipoperoxidatative, and peroxidative). The clinical effect of the use of antioxidants in 38 patients is shown. PMID- 1294797 TI - [The treatment procedure in vesicoureteral reflux in young children]. AB - A group of 54 children with vesicoureteral reflux recognized in the first 3 years of life was analysed. All of them received adequate nonoperative treatment including prolonged antibacterial therapy and management of cystitis and urodynamic disorders of the lower urinary tract. According to the degree of vesicoureteral reflux (VUR), the children were divided into two groups. Group 1 consisted of 29 children with Degrees I-II VUR in 37 ureters. Nonoperative treatment was effective in 75% of cases. Retrospective appraisal of urograms revealed no signs of cicatricial-sclerotic changes in the parenchyma of the kidneys. In five children with Degree II VUR of long duration the kidneys were smaller than the normal size of their age. Group 2 was made up of 24 patients with Degrees III-V VUR into 34 ureters. No changes were found in the renal parenchyma on urograms made during the first examination. During follow-up, however, signs of reflux-nephropathy (RN) were detected, which according to the recommendations of the International group for reflux study were evaluated as Degree I RN--10 cases, Degree II RN--12 cases, Degree III RN--8 cases, and Degree IV RN--4 cases. The authors believe nonoperative treatment of children with Degrees I-II VUR to be justified, patients with Degrees III-V VUR call for active surgical intervention from the moment that the reflux is recognized. PMID- 1294799 TI - [The efficacy of specific plasma in the therapy of newborn infants with a Pseudomonas aeruginosa surgical infection]. AB - 141 newborn with purulent surgical infection were under observation. In 73 the inflammatory process was not induced by Pseudomonas aeruginosa in 68 the infection was caused by the blue pus bacillus. Bacteriological and immunological examination was conducted, including that with the use of enzyme immunoassay, to monitor the optical density of anti-pyocyanea antibodies during the course of the disease. It was found that the serum of a healthy newborn baby contains antibodies to Pseudomonas pyocyanea and did no differ from that of healthy older children in the level of anti-pyocyanea antibodies. The increase of the level of anti-pyocyanea antibodies in response to infection with Pseudomonas pyocyanea is twice less in newborns than older children with this infection. The use of specific plasma is much more effective than the administration of nonhyperimmune plasma. The efficacy of treatment with anti-pyocyanea plasma is determined by the level of anti-pyocyanea antibodies produced in the patient as a result of plasmatherapy rather than the volume of the dose given for the course. PMID- 1294800 TI - [The diagnosis of obstructive cholangiopathy in newborn infants]. AB - To establish an early diagnosis of obstruction of the extrahepatic bile ducts in 12 newborn infants with jaundice the authors applied hepatobiliary scintigraphy and transcutaneous cholecystocholangiography under control of laparoscopy (2 patients). Atresia of the bile ducts was diagnosed in 4 children, which was confirmed during the operation; in one of these patients scintigraphy undertaken 3 weeks after the intervention showed restoration of the flow of bile into the intestine. In 5 cases a mechanical component of jaundice was not found and in 2 newborn infants the results of scintigraphy proved to be poorly informative. Transcutaneous cholecystocholangiography under control of laparoscopy in 2 cases made it possible to avoid laparotomy in suspected atresia of the bile ducts. PMID- 1294801 TI - [The immune status of children with extrahepatic portal hypertension following splenectomy]. AB - The purpose of the work was to study the immune status and some nonspecific defense factors in children with extrarenal portal hypertension after splenectomy. Seventy-one children were examined. It was found that the T lymphocyte count before and in the early periods after the operation in children with extrahepatic portal hypertension did not differ from that in the control group. At the same time, the changes in serum immunoglobulins depended on the stage of the examination. Study of other links of immunity also revealed the time course of changes in their values. PMID- 1294802 TI - [The results of the surgical treatment of thyroid diseases in children]. AB - The results of surgical treatment of various forms of diseases of the thyroid gland in 254 children are analysed in follow-up periods of 12 months to 20 years. Functional compensation of the thyroid occurred in all patients with nodular forms of goiter who were subjected to operation which did not exceed hemithyroidectomy in volume. The analysis showed that operative treatment of children with the diffuse toxic form of goiter attended by the autoimmune component lead to hypothyroidism in 76.6% of patients, whatever the activity of the thyroid tissue, and a recurrence developed in 11.7% of those who were operated on. In children without the autoimmune component postoperative hypothyroidism was found in 48.6% of those examined, a recurrence was found in 3.2% of cases. The indications for operative treatment are specified, measures for the prevention of postoperative complications are listed. PMID- 1294803 TI - [The surgeon's procedure in dystrophic bone cysts in children]. AB - The authors set apart childhood dystrophic cyst as a separate nosological unit. The underlying factor of the development of a bone cyst is dysplasia of vessels filling the bone-marrow canal and a concomitant dystrophic process in the surrounding bone tissue. The nonneoplastic nature of the cysts led to the search for sparing methods of treatment, namely, the puncture method. The administration of demineralized bone shavings during therapeutic puncture (after osteoperforation of the wall, scraping off the fibrous membrane) produces good results. The clinical material consists of 46 cases. There were 8 cases of aneurysmal bone cyst, 23 with active and 15 with passive bone cysts. In 44 cases treatment by two or three punctures led to recovery in 2-4 months. In 2 patients with aneurysmal bone cysts three punctures proved ineffective and an operative intervention was undertaken. It is concluded that treatment by puncture is indicated in dystrophic bone cysts. Operation is indicated in poor outcomes of puncture treatment in patients with aneurysmal bone cysts. PMID- 1294804 TI - [The criminal law responsibility of the physician in the FRG]. PMID- 1294805 TI - [The conservative treatment of acute hematogenous osteomyelitis in children]. AB - Radioisotopes were used to study the water spaces of the bone and bone marrow in 47 dogs with a created model of acute osteomyelitis. By the 3rd-5th day of experimental osteomyelitis sharp hyperhydration of the bone marrow and bone proper was revealed which was caused by a 2.5-2.8-fold increase of the volume of intercellular fluid in the zone of the affection, leading to circulatory disorders and necrosis. Dehydration of the tissues is accomplished by inflicting numerous percutaneous osteoperforations (NPO) with Kirschner's wire. The osteoperforations are made not at random but in a regular manner through both walls of the bone in two interperpendicular planes. Circulation in the zone of the affection is restored in this case and osteonecrosis in prevented. Conservative methods of treatment of acute hematogenous osteomyelitis were developed according to the stage of its development and were applied in 168 patients whose ages ranged from 20 days to 14 years; in 75% of patients who were admitted in the early stages of AHO the disease took and abrupt course. In patients with neglected forms of AHO three-fourfold infliction of NPO in the subacute stage produced a stimulating effect on reparative regeneration in the zones of osteonecrosis and the forming sequestra. PMID- 1294806 TI - [Arthropneumography in the diagnosis of meniscal diseases in children]. PMID- 1294807 TI - [The treatment of intestinal fistulae in children by applying a by-pass anastomosis using magnetic devices]. AB - A new method is suggested for the exclusion of intestinal fistulas by the formation of by-pass anastomoses by means of a permanent magnet. The variants of the techniques of magnet by-pass anastomoses are discussed. The results of treatment of 46 children with external intestinal fistulas are shown. With the formation of a by-pass compression anastomosis the mortality rate among children with intestinal fistulas reduced from 31 to 13%. PMID- 1294808 TI - [Neurogenic lung tumors]. PMID- 1294809 TI - [Conjoined twins]. PMID- 1294810 TI - Enzymatic properties of ubiquitously expressed delta-subspecies of protein kinase C differing from other members of protein kinase C family. AB - The delta-subspecies of protein kinase C (PKC) was purified to near homogeneity from the Triton X-100 extract of the rat brain particulate fraction by successive chromatographies on S-Sepharose Fast Flow, Phenyl 5PW, Heparin 5PW, hydroxyapatite, and Mono Q columns. The purified enzyme was doublet with molecular weight of 78 kDa and 76 kDa on SDS-PAGE. This doublet proteins were separated partially by Mono Q column chromatography, both of which were recognized by the antibodies raised against synthetic oligopeptides, parts of the deduced amino acid sequence of the rat delta PKC. Protein phosphatase 2A treatment suggested that the 78 kDa protein was a phosphorylated form of the 76 kDa protein. To confirm the structural and genetic identity of the doublet proteins, delta PKC was expressed in COS 7 cells by transfecting its cDNA constructed plasmid, and was purified for comparison. This recombinant enzyme was also doublet. The enzymes isolated from the brain and COS 7 cells showed identical reactivities with delta PKC-specific antibodies, chromatographic behaviors, and V8 protease peptide mapping. In addition, these the enzyme preparations were indistinguishable from each other in their responses to phosphatidylserine, diacylglycerol, phorbol esters, free fatty acids, and Ca2+. Comparison was also made between the enzymological properties of delta PKC and alpha PKC, such as activation kinetics, sensitivity to protein kinase inhibitors and substrate specificity which were distinctly different from each other. PMID- 1294811 TI - Susceptibility of Aedes albopictus mosquitoes (Oahu strain) to infection with Dirofilaria immitis. AB - The susceptibility of the Oahu strain of Aedes albopictus mosquitoes to infection with Dirofilaria immitis was examined to study the development of larvae in detail. Most of the developing larvae were found in the Malpighian tubules and infective larvae in the labium, indicating that Aedes albopictus Oahu strain is susceptible to the infection with D. immitis. New different patterns of development from those reported by earlier studies were observed: (i) the second stage larvae in the thorax muscles of the mosquitoes and (ii) a small projection from the head of the sausage-form first-stage larvae. PMID- 1294812 TI - Protein kinase C subspecies in rat brain synapses and phosphorylation of growth associated protein. AB - Synaptosomes isolated from rat hippocampus contained the alpha- and beta subspecies of protein kinase C (PKC), but not the gamma-subspecies, whereas postsynaptic pyramidal cells contained all these three subspecies. The PKC enzymes were activated synergistically by diacylglycerol and cis-unsaturated fatty acids including docosahexaenoic acid which is abundant in brain phospholipids. The phosphorylation of a PKC-specific substrate, growth-associated protein (GAP-43), which is associated predominantly with presynaptic membranes, was also protein (GAP-43), which is associated predominantly with presynaptic membranes, was also stimulated by diacylglycerol and cis-unsaturated fatty acids, particularly at the micromolar range of Ca2+ concentrations. The results presented suggest that cis-unsaturated fatty acids together with diacyglycerol may take part in the phosphorylation of GAP-43 in presynaptic membranes presumably by the alpha- or beta-subspecies of PKC even after the Ca2+ concentrations return to the basal level. PMID- 1294813 TI - [Myocardial infarct in young women]. PMID- 1294814 TI - [The role of heredity in esophageal diseases]. PMID- 1294815 TI - [Antineutrophil cytoplasmic antibodies in systemic vasculitis]. PMID- 1294816 TI - [The characteristics of cardiomyopathy in different geographical regions]. AB - Region-specific characteristics of hypertrophic cardiomyopathy (HC) and dilated cardiomyopathy (DC) were compared for 108 relevant patients living in Dubai (United Arab Emirates) and Moscow (Russia). Out of 49 citizens of Dubai 17 had HC, 32 DC, and 59 Moscow patients had HC in 23, DC in 36 cases. It was found that HC in Dubai tends to run a silent latent course, involving mainly basal septum and right ventricle. Apical lesions were more typical for Moscow citizens who also display more severe myocardial impairment. DC in Dubai produces weaker cardiac insufficiency and arrhythmia. Incidence of idiopathic and periportal DC proved higher in Dubai, while alcohol and virus infection underlie DC more frequently in Moscow. PMID- 1294817 TI - [The clinical efficacy of plasmosorption in stenocardia]. AB - Follow-up examinations of 52 anginal patients who have received combined treatment involving plasma sorption indicate a good response in 77%, satisfactory in 11.5% and no response in 11.5% of the examinees. Exercise tolerance and performance increased by 34.3 and 52.1%, respectively. The scope of chemotherapy was related to the initial severity of the disease. Clinical remission after plasma sorption lasted 8.4 +/- 0.7 months. PMID- 1294819 TI - [The diagnosis and endoscopic removal of foreign bodies obstructing the esophageal lumen]. AB - The authors present a sequence of diagnostic (the patients' complaints, case history, clinical, x-ray and endoscopic evidence) and therapeutic (endoscopic treatment) measures to be taken in order to remove foreign bodies responsible for esophageal obstruction. The policy proposed allows the physicians to avoid misdiagnosis and to clear away foreign bodies from the esophagus with minimal complications in 96% of the cases. PMID- 1294818 TI - [Treatment experience with rheumatoid arthritis patients during remission]. AB - 94 rheumatoid arthritis (RA) patients were observed for 4-5 years to evaluate the effect of basic treatment and opportunities for prolonged remission. A regimen of combined treatment has been tested which allows for psychologic status of the patient, corrects weak points in the regulatory systems, affects mechanisms of nonspecific resistance. The combined treatment administered during RA remission has resulted in complete responses (remissions) more frequently, prolonged their duration. Destructive processes in the joints still present in remission were seen to slow down. PMID- 1294820 TI - [The surgical procedure in patients with hemorrhaging perforating gastroduodenal ulcers]. AB - The paper presented the results of surgical treatment of 277 patients with bleeding penetrating gastroduodenal ulcers. Gastric location of the ulcer was revealed in 52 patients and duodenal location in 225 ones. More commonly used resections of the stomach according to a Billroth-I method or suprapyloric resections versus the resection of the stomach according to method Billroth-II when used in the patients with gastric location of the ulcers helped to reduce the mortality from 23.1 to 0%. The wide usage of organ-sparing operations combined with vagotomy reduced the lethal outcomes of the disease from 13 to 5.5% versus the resection of the stomach. The rate of bleeding relapses in the early postoperative period which followed the suture of penetrating gastroduodenal ulcers was 25.9%. The dissection of ulcers or their elimination from the alimentary tract could be regarded as the methods of choice in case of palliative treatment. Surgical treatment of penetrating gastroduodenal ulcers should be performed prior to bleedings. Planned operative intervention should be performed in patients with deep gastric ulcer with diameter of 1.5 cm and more and pyloroduodenal ulcers with diameter of more than 1 cm. PMID- 1294822 TI - [The comparative efficacy of ranitidine and famotidine in treating exacerbations of duodenal peptic ulcer]. PMID- 1294821 TI - [The computerized evaluation of the signs of duodenal peptic ulcer]. AB - A mathematical analysis of the data bank collected on duodenal ulcer patients has been performed using adapted to computer processing coded disease histories. Most informative signs of ulcerogenesis, diagnostic indicators of peptic ulcer have been selected and ranged. The review of peptic ulcer diagnostic criteria is presented. PMID- 1294823 TI - [The prevention of ischemic stroke: the neurological and angiosurgical aspects]. PMID- 1294824 TI - [Acute cholecystitis in the clinical picture of acute food poisonings]. AB - The authors followed up 215 patients with acute cholecystitis who were hospitalized with an erroneous diagnosis of food poisoning and 346 food poisoning patients who developed acute cholecystitis in the course of the disease mentioned. Symptoms for differential diagnosis of acute cholecystitis and food poisoning were considered. PMID- 1294825 TI - [A new approach to the antibacterial therapy of chronic antral gastritis associated with Helicobacter pylori]. AB - The authors proposed an original method of treatment for antral gastritis associated with Helicobacter pylori and combined with duodenal ulcer. The principle of the method consists in a successive gastric lavage with alkaline and antibacterial (metronidazole) solutions twice a week for a fortnight. Three groups of patients were under observation (37 examinees with chronic antral gastritis associated with Helicobacter pylori and combined with duodenal ulcer). Ten persons who were enlisted into the first group were treated with the lavage only, the second group persons (n = 12) were treated with lavages and histodyl in a dose of 400 mg per night, the third group (n = 15) were orally treated with metronidazole (0.25 g three times a day) for 15 days. A total elimination of Helicobacter pylori was observed in the half of the first group, 2/3 of the second and in 1/3 of the third group. Epithelialization of duodenal ulcers was observed in all those enlisted in the first and second group. Cicatrization of ulcers was observed in half of the patients from the third group. PMID- 1294826 TI - [The diagnostic potentials of an immunological method for detecting Helicobacter (Campylobacter) pylori]. PMID- 1294827 TI - [Familial Itsenko-Cushing disease]. PMID- 1294828 TI - [The transport of sodium, water and active osmotic substances in different parts of the nephron of patients with chronic glomerulonephritis and hypertension]. AB - The lithium test was conducted to evaluate transport of water, sodium and osmotic active substances in 46 chronic glomerulonephritis (CG) patients. Sixteen CG patients entered group 1. All of them had secondary hypertension (SH). Twelve CG patients with SH symptoms of moderate reduction of endogenic creatinine clearance were assigned to group 2. Twelve patients of group 3 had CG and isolated urinary syndrome. Group 4 consisted of 6 patients with essential hypertension. As shown by the test, association of SH and CG is not an essential factor for renal transport of sodium, water and electrolytes. Some shifts in the transport in group 2 are attributed to reduced number of functioning nephrons. The tendency to enhanced lithium clearance was registered in group 4. This may reflect an increased supply of sodium, water and osmotic active substances to the uriniferous tubules. PMID- 1294829 TI - [Metastases of thyroid cancer to the heart simulating a myocardial infarct]. PMID- 1294830 TI - [A multiyear favorable course of an untreated rheumatic defect of the mitral valve]. PMID- 1294831 TI - [An evaluation of the efficacy of dispensary care as a method for the active detection of skin melanoma]. PMID- 1294832 TI - [Is an expansion of the concepts of so-called iatrogenic diseases valid?]. PMID- 1294833 TI - [Chronic bronchitis and pulmonary emphysema]. PMID- 1294834 TI - [In the tracks of World War II (the memoirs of an infectious disease specialist- a participant in the war)]. PMID- 1294835 TI - Identification and quantitation of cocaine and its metabolites, benzoylecgonine and ecgonine methyl ester, in hair of Bolivian coca chewers by gas chromatography/mass spectrometry. AB - Twenty hair samples obtained from Bolivian mine workers who chewed 3-8 g of coca leaves daily for several years were analyzed for cocaine and its main metabolites, benzoylecgonine (BZE) and ecgonine methyl ester (EME). A new method was developed for the detection and quantitation of cocaine and its metabolites, BZE and EME, from hair in a single procedure. The hair samples were washed, cut into 56 segments (2-cm length), pulverized, and incubated with phosphate buffer and the enzyme beta-glucuronidase-arylsulfatase. After solid phase extraction and derivatization with pentafluoropropionic anhydride/pentafluoropropanol, the drugs were identified and measured by gas chromatography/mass spectrometry (GC/MS) using deuterated cocaine, BZE, and EME as internal standards. The method is reproducible (cocaine, CV = 8%; BZE, CV = 14%) and the detection limit for cocaine and BZE was 0.1 ng/mg, for EME 1 ng/mg. In the different hair segments, cocaine was found to be present in concentrations between 1.4 to 50.6 ng/mg, benzoylecgonine from 0.4 to 17.6 ng/mg, and ecgonine methyl ester traces below the calibration curve of approximately 12.9 ng/mg. In 95% of the cases cocaine exceeded BZE and EME in concentration. PMID- 1294836 TI - Concentration of cocaine and metabolites in plasma of humans following intravenous administration and smoking of cocaine. AB - Plasma was obtained from 10 human subjects at various intervals after administration of two rapid doses of cocaine, either intravenously or by smoking, and multiple doses by smoking and intravenously. The plasma was analyzed for COC and its metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME). Plasma concentrations of COC were found to be dose-dependent. For patients receiving two successive doses of COC intravenously (IV) or by smoking (SM), the average half life of COC was found to be between 38 and 39 minutes, regardless of the dose or route of administration. Considerable interindividual variation was observed. Multiple doses of both SM and IV COC were administered to three patients in a manner consistent with COC abuse. The maximum COC concentration observed was 1.2 mg/L following a total administration of 316 mg of COC over 90 min. Analysis of BE and EME confirmed that BE is the principle metabolite of COC in blood. All COC was accounted for by BE. EME, when present, did not exceed 5% of the BE concentration. PMID- 1294837 TI - A simplified procedure for the determination of free codeine, free morphine, and 6-acetylmorphine in urine. AB - A procedure for detection and quantification of free codeine, free morphine, and 6-acetylmorphine in urine is presented. The analytes were extracted at neutral pH by solid-phase extraction prior to derivatization to their trifluoroacetyl derivatives. The derivatized extracts were analyzed by gas chromatography/mass spectrometry in the electron impact mode. Confirmation of the analytes was accomplished by comparing the ion abundance ratios of the analytes to those of a previously analyzed standard. The qualitative ion abundance ratios were required to be within 20% of those of the standard for acceptance. Quantification was based on the tri-deuterated analogs of the analytes. Linearity was obtained in the range of 10 to 1000 ng/mL, with correlation coefficients of all analytes exceeding 0.999. Percent recoveries were 90% for codeine, 88% for morphine, and 85% for 6-acetylmorphine. No hydrolysis of 6-acetylmorphine occurs during the extraction procedure. The authors also studied the stability of 6-acetylmorphine at various storage conditions of pH, temperature, and chemical preservation. 6 Acetylmorphine was found to be stable for 12 weeks when stored at -17 degrees C. PMID- 1294838 TI - The role of ecgonine methyl ester in the interpretation of cocaine concentrations in postmortem blood. AB - A study of the metabolism of in vivo cocaine (COC) and the stability of in vitro COC suggests that the presence of benzoylecgonine (BE) in unpreserved blood arises from in vivo COC metabolism and that ecgonine methyl ester (EME) in unpreserved blood arises from in vitro COC hydrolysis. Postmortem cases positive for COC were studied to determine if molar concentrations of EME in unpreserved blood could be used to estimate the blood COC concentration at the time of death when added to the molar COC concentrations. COC was analyzed in 10 postmortem blood specimens between 1 and 8 days following death and again 10 to 70 days after further storage. The COC lost was accounted for by its hydrolysis to EME. Good correlation (r = 0.9677, p < 0.001) was observed when the blood COC concentrations in postmortem cases were compared to blood COC concentrations predicted by the addition of blood COC and EME concentrations; hence, analysis for EME and estimation of perimortem COC concentrations can assist in defining deaths associated with COC use. PMID- 1294839 TI - Field performance of current generation breath-alcohol simulators. AB - The between-run accuracy and reproducibility of vapor-alcohol control tests associated with quantitative evidential breath-alcohol testing in the field were evaluated. Control samples were generated at six separate sites with 34 degrees C TOXITEST II breath-alcohol simulators and analyzed by infrared spectrometry with Model 5000-D intoxilyzers in the recirculation mode. Control test results at target alcohol concentrations of 0.060, 0.080, 0.090, 0.100, 0.110, and 0.120 g/210 L (n = 779) were combined and analyzed by standard statistical methods. Results were correlated with target values, and the signed and absolute differences were calculated and analyzed. Data treatment included ANOVA, linear regression analysis, t statistics, and relative and cumulative frequency distributions of the differences. We found the performance of these current generation simulators in the field to be similarly satisfactory to that obtained in our laboratory evaluation. We further found that vapor-alcohol control samples generated with these devices conformed to established formal requirements and that they can serve as an effective quality assurance measure in evidential breath-alcohol analysis. PMID- 1294840 TI - Detection of cocaine and its metabolites in human amniotic fluid. AB - The dramatic rise in maternal drug abuse and the incidence of positive drug findings during neonatal testing has increased the need for prenatal toxicological testing for drugs of abuse. Human amniotic fluid samples collected after 13-39 weeks of pregnancy were screened for cocaine metabolite (benzoylecgonine) by fluorescence polarization immunoassay (FPIA). All positive samples, as well as any accompanying maternal serum, were confirmed by gas chromatography/mass spectrometry (GC/MS) for cocaine and its metabolites. Five samples out of 450 were positive for cocaine, benzoylecgonine, and ecgonine methyl ester by GC/MS. In addition, one sample was also positive for cocaethylene. Two maternal serum samples were positive for benzoylecgonine and ecgonine methyl ester. The presence of cocaine, benzoylecgonine, ecgonine methyl ester, and cocaethylene in the amniotic fluid suggests that the fetus is exposed to cocaine and its metabolites through maternal circulation. The impact of this exposure on the health of the newborn is unknown. PMID- 1294841 TI - Feasibility of using GC/FT-IR for drug analysis in the forensic toxicology laboratory. AB - New developments in cryogenic sample deposition for gas chromatography/Fourier transform infrared (GC/FT-IR) spectroscopy have increased the sensitivity of the technique 100-1000-fold, to match or surpass that of gas chromatography/mass spectrometry (GC/MS). The current methods of GC/MS have led to some false positive identifications in drug testing labs. New methods employing GC/FT-IR will provide absolute identification through infrared fingerprinting with routine detection in the ppb range. GC/FT-IR methods are being developed which indicate low picogram amounts of material are detectable. Some preliminary data have shown that reference-quality spectra can be obtained from samples containing 200 ng/mL of amphetamines, and spectra from samples below the 25 ng/mL level for amphetamines can be obtained for identification purposes. These and other applications will be addressed along with limit of detection (LOD), limit of quantitation (LOQ), and linearity in comparison to commonly used techniques. PMID- 1294842 TI - Solid phase extraction of phencyclidine from urine followed by capillary gas chromatography/mass spectrometry. AB - This communication describes a method for the solid phase extraction of phencyclidine (PCP) from urine, followed by GC/MS analysis. The method is linear over the range 5-1000 ng/mL and consistently produces cleaner chromatograms than can be obtained by liquid-liquid extraction. The limits of detection and quantitation are 0.47 and 1.38 ng/mL, respectively. Extraction efficiency, or recovery, was found to be 100.8 +/- 6.5%, and the between-run precision was 3.5% (25 ng/mL, n = 51). This solid phase method for extraction of PCP from urine has several advantages over liquid-liquid extraction for laboratories of any size. PMID- 1294843 TI - Whole blood deproteinization for drug screening using automatic pipettors. AB - Automating the initial screening of postmortem blood and other tissues for drugs of abuse requires a pipetting procedure that is compatible with immunoassay screening tests. The deproteinization procedure uses a zinc sulfate-5 sulfosalicylic acid reagent to precipitate blood proteins. This procedure for deproteinization of whole blood and tissue homogenates is compatible with coated tube radioimmunoassays (RIA) and can therefore be used in automating the initial screening step. PMID- 1294844 TI - Tissue distribution of bupropion in a fatal overdose. AB - A fatality resulting from the ingestion of bupropion is reported. Quantitation of bupropion and its metabolites was accomplished by gas chromatography. The distribution of bupropion and its metabolites, along with analytical details, is presented. PMID- 1294845 TI - Group selection, individual selection, and the evolution of genetic drift. AB - In a subdivided population, genetic drift affects variation between groups, and thus it can have an important effect on the outcome of evolution (Wright, 1978). The rate of genetic drift is determined, in part, by the behaviour of population members. This paper presents three mathematical models in which behavioural traits that affect the rate of genetic drift are allowed to coevolve with traits that are under selection at the group and individual levels. The results show that if group selection is strong relative to individual selection, then behavioural traits that enhance the rate of genetic drift will tend to increase in frequency. The strength of this effect depends, in part, on the way in which vacant sites are colonized. PMID- 1294846 TI - On the origin of the transfer RNA molecule. AB - Data and arguments are given in favour of the hypothesis that the primitive tRNA molecule may have originated from a direct duplication event involving one of the two halves of the tRNA molecule. It seems that a molecule capable of assuming a hairpin structure was involved as a precursor in this duplication. The two halves of the present tRNAs could, therefore, be considered as paralogous. PMID- 1294847 TI - The evolution of regeneration: adaptive or inherent? AB - If regeneration were adaptive, it would have arisen autonomously by natural selection from non-regenerative antecedents. Unless each episode coincidentally reinvented the same method of regeneration independently, one would expect the various lineages to differ basically from each other, which they do not. On the other hand, if regeneration were inherent to metazoan life, a derivative of embryogenesis, its various expressions should be as much like each other as they resemble the development of embryonic appendage buds, which they do. It follows that the uneven distribution of regeneration must have been due to its extinction here and there, not as a negative adaptation by natural selection but as a pleiotropic epiphenomenon linked to more useful adaptations with which it was incompatible. In vertebrate evolution, these adaptations have included the transition from aquatic to terrestrial habitats and the modification of poikilothermic to homeothermic metabolism. The former advance rendered the regeneration of weight-bearing limbs impractical; the latter favored rapid wound healing and scar formation which effectively precluded blastema formation. If the latent capacity for regeneration persists in non-regenerative appendages, as would seem to be the case, then the restoration of its overt expression should be possible if the mechanisms of its inhibition could be discovered and eventually rendered ineffectual. PMID- 1294848 TI - Relationships between chromosome segregation, cell shape and temperature in Escherichia coli. AB - The partitioning of chromosomes into daughter cells during the division of Escherichia coli is non-random. As a result, the chromosome containing the older template DNA strand has a higher probability of segregating toward the old cell pole than toward the new cell pole. The numerical value of this probability is a function of the incubation temperature. It is shown here that a recent model for explaining the physiological basis for non-random chromosome segregation also explains the temperature dependence of the segregation process. PMID- 1294849 TI - Dimensional optimization at different levels of the arterial hierarchy. PMID- 1294850 TI - Modification of a consumer digital audio tape (DAT) for analog data recording. AB - A modification of a commercially available digital-audio tape (DAT) for DC recordings such as those used in patch clamp and other electrophysiological experiments is introduced. The modified DAT can record data from 2 channels plus a separate trigger signal for up to 2 h. The bandwidth ranges from direct current to 21 kHz; the signal-to-noise ratio is above 90 dB and the A-D resolution is 16 bit. A 120-min cassette yields a storage capacity of 1.4 Gbytes. The trigger is 'hidden' on 1 channel as a burst of 1-ms duration, thus minimizing interference with the recorded data. The modified DAT offers a low-cost yet high quality solution to most analog data storage needs. PMID- 1294851 TI - Hyperthermia-induced damage to rat sciatic nerve assessed in vivo with functional methods and with electrophysiology. AB - A 5-mm segment of the rat sciatic nerve was treated in vivo with hyperthermia (43 45 degrees C) for different times using a brass thermode. The effect of this local heat treatment on the nerve was assessed with electrophysiology and using two functional assays. Hyperthermia led to a dose-dependent decrease of motor and sensory function. Electrophysiological examination showed a decrease in amplitude of motor and reflex responses rather than a decrease in conduction velocities. Calculated ED50 values were not significantly different for the two functional and for the electrophysiological methods. Functional recovery from nerve damage took place in all cases. Measured at the same level of damage, i.e., 50% function loss, it took 14 days to recover from complete sensory function loss and 20 days from complete motor function loss. Although both motor and sensory functions were restored, 30 days after hyperthermia no responses could be detected with electrophysiology, this as a result of the thin myelin sheaths that occur upon recovery. PMID- 1294852 TI - Detection of complement protein mRNA in human astrocytes by the polymerase chain reaction. AB - Primer sets specific for complement proteins, C3, factor B and factor I, were designed and used to amplify cDNA from cultured human astrocyte mRNA by the polymerase chain reaction. Appropriately sized PCR products of 506 bp, 885 bp and 146 bp, respectively, were generated and specificity was confirmed with Southern blotting using an enhanced chemiluminescence detection system. The sensitivity of detection was high, with amplified product from cDNA of approximately 6250 cells readily visualized. C3 and factor B have previously been reported to be produced by murine astrocytes; however, this is the first report indicating synthesis of C3, factor B and factor I by human astrocytes. These results indicate that PCR is a simple and sensitive technique to detect mRNA transcripts for proteins of the alternative pathway of complement in human astrocytes. PMID- 1294853 TI - Computer-assisted alignment of standard serial sections without use of artificial landmarks. A practical approach to the utilization of incomplete information in 3 D reconstruction of the hippocampal region. AB - An algorithm for the alignment of stained serial sections without the support of artificial landmarks is described. Four-hundred-thirty serial sections of the rabbit hippocampal region were digitized, and computer-based alignment was performed without use of artificial markers, resulting in a consistent matrix. Following proper filtration, artificial sections were cut through the matrix. In a second experiment every second image was deleted and reconstructed by interpolation with a minor loss of biological information. In a third experiment every second image was deleted and the rest of the images were 'disordered', realigned and the missing planes reconstructed by interpolation. Under these circumstances the matrix was reconstructed with some loss of information. These results may widen the limits of 3-dimensional (3-D) reconstruction, as routine histological preparations normally include only every second or every third section without artificial landmarks. PMID- 1294854 TI - New transducers for measuring muscle length in unrestrained animals. AB - Muscle length in unrestrained, chronically implanted animals is conventionally measured with gauges consisting of a compliant silicone rubber tube filled with either hypertonic saline or mercury, the measurement principle being a continuous change in the electrical resistance of the fluid column inside the tubing with stretch. These gauges have two major disadvantages: (1) changes in resistance that are not related to changes in length, such as those produced by changes in temperature or osmotic dilution of the hypertonic saline, cause the measurements to drift, and (2) there is no direct and accurate way to calibrate the measurements. In this communication two new types of muscle length gauge are described that eliminate both problems. Both types make use of the principle of sonomicrometry, i.e., the measurement of distances with pulsed ultrasound. Both types have been successfully used to measure the length of the medial gastrocnemius muscle in chronically implanted cats during treadmill locomotion. PMID- 1294855 TI - Species differences in platelet aggregation induced by platelet-activating factor (PAF). AB - Species differences in platelet aggregation induced by platelet-activating factor (PAF) were investigated by using the same procedure of platelet preparation and biological assay. Washed platelets of six different species (horses, dogs, rats, rabbits, sheep and guinea pigs) were prepared employing the same method and platelet aggregation was induced by C16-PAF. Horse platelets were most sensitive to PAF (8.0 x 10(-12) M) and rabbit platelets activated by 5.0 x 10(-11) M PAF were also sensitive enough to detect PAF in clinical samples. PMID- 1294856 TI - Histamine leukocytosis. I. Effect of histamine on peripheral leukocyte counts. AB - The effect of chronic administration of histamine on the number of cells in peripheral blood of dogs, rabbits and guinea pigs was tested by single and consecutive intramuscular injections of histamine in a beeswax-sesame oil mixture. Leukocytosis due to increased numbers of neutrophils occurred in all animals after single injections of histamine in beeswax, although erythrocytes and hematocrit values were unaffected in all species. When injection of histamine was repeated on consecutive days, the extent of leukocytosis subsided in some cases; however, the simultaneous administration of aminoguanidine restored leukocytosis. Single or daily injections of the beeswax-sesame oil mixture without histamine had none of these effects in any animals tested. Although simultaneous injections of histamine and H1 receptor antagonists did not alter histamine effects, the combined administrations of histamine and H2 receptor blocking agents suppressed histamine-induced leukocytosis. PMID- 1294857 TI - The effect of naloxone on restraint-induced antinociception in mice. AB - Restraint for a period from 15-60 min induced significant antinociceptive effect in both male and female mice. The restraint animals all showed an increase in response time to the hot plate test at 55 degrees C. The antinociceptive activity was still apparent one hour after restraint. In the male animals, prior administration of naloxone s.c. 15 min before restraint for 60 min did not affect the degree of antinociceptive activity induced by restraint. In addition, naloxone administered s.c. immediately after restraint for 60 min also did not affect the degree of antinociceptive activity in male mice. These findings indicate that in male animals the endogenous opioid mechanism is most likely not involved in the restraint-induced antinociception. However, for the female mice naloxone administered s.c. either before or immediately after restraint for 60 min dose-dependently suppressed the antinociceptive activity induced by restraint. It is concluded that restraint can induce antinociceptive activity in mice; however, different mechanisms may be involved in the antinociception observed. In male mice the endogenous opioid systems do not seem to play a significant role in restraint-induced antinociception, while for female animals blockade of opioid receptors would greatly diminish the antinociception observed after restraint. PMID- 1294858 TI - The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. I. General characteristics. AB - A single-pass perfused rabbit ear was employed as the model for studying percutaneous absorption of clonazepam in an open perfusion system. Clonazepam at 1.5% concentration (w/w) was suspended in a gel containing 1% (w/w) neutralized Carbopol 934 vehicled by a 50% water solution of propylene glycol and applied to the skin, in a thermostatically controlled chamber, after 10 min pretreatment with a lauryl alcohol enhancer. At 32 degrees C, the amount of clonazepam which diffused into the effluent after a 3 h lag phase was constant for 3 h and the flux averaged 0.486 mcg/h/cm2, whereas at 25 degrees C, the flux averaged 0.424 mcg/h/cm2. The amount of drug diffusing into the effluent was a function of the contact surface area and was independent of the rate of perfusion up to values of 1 ml/min. The apparent diffusion coefficient, Ds, and the partition coefficient, KM, were 2.75/10(6)/cm/h and 5.21, respectively. PMID- 1294859 TI - Serum histamine in Alzheimer's disease and multi-infarct dementia. AB - Recent data indicate that a neuroimmune reaction might be responsible in part for neuronal death and cognitive deterioration in senile dementia. The potential involvement of brain histamine (HA) and interleukin-1 (IL-1) in this process has been previously documented. We have studied the concentration of serum HA in patients with Alzheimer's disease (AD) or multi-infarct dementia (MID) and in age matched control subjects. Serum HA levels were significantly higher in AD (10.935 +/- 5.692 nM) and MID (8.521 +/- 3.44 nM) than in controls (5.533 +/- 2.567 nM) and correlated with mental performance as evaluated with the Mini-Mental State Examination (MMSE) (r = +0.493, p < 0.009). No correlation was found with cardiovascular parameters, cerebrovascular risk factors or age. Hyperactivation of the histaminergic system in AD at central and peripheral levels might reflect a neuroimmune reaction to brain tissue damage, a neurotrophic response, and/or a reactive process to regulate the IL-1 induced amyloid precursor protein (APP) overproduction. PMID- 1294860 TI - Investigation of the pharmacokinetic behavior of barucainide in man during an early phase I study. AB - The pharmacokinetic behavior of the class Ib antiarrhythmic drug barucainide was investigated in a phase I study in a group of 6 healthy male volunteers after oral administration of an initial single dose of 20 mg and incremental doses between 30 and 70 mg barucainide hydrochloride. After a lag time of about 1 h, median plasma concentration peaked at ca. 48 ng/ml barucainide hydrochloride 2.5 h after administration of 20 mg. The drug was finally distributed in a total volume of VB/f of about 630 l. With a terminal half-life of ca. 12.5 h (8-26 h) it was eliminated rather slowly. Elimination was predominantly due to metabolic processes; however, a median of 21% of the dose (7-28%) was recovered unchanged in the urine. Barucainide, in the dose range studied, was not subject to any appreciable first-pass effect; its metabolism apparently depended on the hydroxylation capacity of the volunteers. The doses administered were well tolerated. There were no changes in the cardiovascular parameters investigated, no adverse effects and no impairment of general well-being. PMID- 1294861 TI - Shi-quan-da-bu-tang (ten significant tonic decoction), SQT. A potent Chinese biological response modifier in cancer immunotherapy, potentiation and detoxification of anticancer drugs. AB - Shi-Quan-Da-Bu-Tang (Ten Significant Tonic Decoction), or SQT (Juzentaihoto, TJ 48) was formulated by Taiping Hui-Min Ju (Public Welfare Pharmacy Bureau) in Chinese Song Dynasty in AD 1200. It is prepared by extracting a mixture of ten medical herbs (Rehmannia glutinosa, Paeonia lactiflora, Liqusticum wallichii, Angelica sinesis, Glycyrrhiza uralensis, Poria cocos, Atractylodes macrocephala, Panax ginseng. Astragalus membranaceus and Cinnamomum cassia) that tone the blood and vital energy, and strengthen health and immunity. This potent and popular prescription has traditionally been used against anemia, anorexia, extreme exhaustion, fatigue, kidney and spleen insufficiency and general weakness, particularly after illness. In order to restore immunity in cancer patients, potentiate the therapeutic effect and ameliorate adverse toxicity of anticancer agents, 116 Chinese herbal formularies (Kampo) have been screened and evaluated. Fifteen compounds were found to have such actions. Among these, SQT was selected as the most effective as a potent biological response modifier. During the last eight years, animal models and clinical studies have revealed that SQT demonstrates extremely low toxicity (LD50 > 15 g/kg op murine), self-regulatory and synergistic actions of its components in immunomodulatory and immunopotentiating effects (by stimulating hemopoietic factors and interleukins production in association with NK cells, etc.), potentiates therapeutic activity in chemotherapy (mitomycin, cisplatin, cyclophosphamide and fluorouracil) and radiotherapy, inhibits the recurrence of malignancies, prolongs survival, as well as ameliorate and/or prevents adverse toxicities (GI disturbances such as anorexia, nausea, vomiting, hematotoxicity, immunosuppression, leukopenia, thrombocytopenia, anemia and nephropathy, etc.) of many anticancer drugs. The application and mechanistic studies of SQT in future development have potential importance in basic and clinical research of the traditional Chinese therapeutic approach of "toning the blood and strengthening Qi (vital energy)" in cancer immunotherapy. PMID- 1294863 TI - The application of theory in medical anthropology: an introduction. PMID- 1294862 TI - How to discuss ethics in institutional review boards? PMID- 1294864 TI - Biocultural synthesis in medical anthropology. AB - Medical anthropology has developed distinct and separate biological and cultural approaches to the study of health and disease in human populations. Within cultural anthropology a major focus has been the ethnomedical perspective that analyzes the process of defining disease and describing the social response to disease. In biological anthropology, an ecological perspective considers the interaction of the population, the insult and the environment at the core of the disease process. There has been limited success in integrating the cultural and biological perspective. Some cultural anthropologists claim that the ecological perspective relies on a biomedical model and therefore is not useful in studying non-Western societies. Others are critical of the adaptivist perspective that they believe fails to consider political economic factors that affect the disease process. The lack of a biocultural integration has hindered the systematic analysis of health and disease in contemporary traditional and non-Western groups. An ecological model that addresses these problems will provide a biocultural integration of the disease process. PMID- 1294865 TI - Why does Juan Garcia have a drinking problem? The perspective of critical medical anthropology. PMID- 1294866 TI - Toward an ecology of women's reproductive health. AB - Medical ecology has been one of the dominant theoretical strands in medical anthropology since the 1960s. It has come to be identified with a rather narrow range of research issues, concerning such matters as adaptation to climate and infectious disease, and has dealt with small-scale foraging societies. An ecological model has potential for dealing broadly with other health issues, in the case explored here, women's reproductive health, a topic that has frequently been approached from either a cultural or biological standpoint rather than the integrated one advocated here. PMID- 1294867 TI - Postischemic breakdown in hippocampal protein synthesis and mnesic deficits in rats: pharmacological improvement by curative naftidrofuryl treatment. AB - This work was designed to investigate the effects of brain ischemia on mnesic retention in the model of unilateral microsphere embolization in rats. Using various radioactive tracers as well as a learning/memory test, we could correlate following parameters: regional blood flow, protein synthesis and memory retention. All were severely impaired by the hemispheric multi-infarction. A curative treatment with naftidrofuryl (15 mg/kg i.p.) for 3 consecutive days strongly improved the mnesic capacities of the animals, and this effect was corroborated by a marked protective drug action on protein synthesis in the hippocampus. Indeed, studies on valine incorporation into proteins revealed that, despite having no quantitative effect on regional blood flow, naftidrofuryl allowed an almost normal functioning of protein synthesis. As naftidrofuryl had also no direct effect on protein synthesis in the intact contralateral hemisphere, this effect was consequently attributed to the metabolic and/or antiserotoninergic effects of the drug. PMID- 1294868 TI - Astrocyte volume regulation and ATP and phosphocreatine concentrations after exposure to salicylate, ammonium, and fatty acids. AB - Cellular volume regulation following swelling in hypo-osmotic phosphate-buffered saline (PBS) and ATP and phosphocreatine concentrations of cells incubated in iso osmotic or hypo-osmotic PBS were measured in primary cultured rat cerebral astrocytes exposed for 30 min to NH4Cl, salicylate, hexanoate, octanoate, and/or dodecanoate. These compounds have been implicated in the pathogenesis of cerebral edema in Reye's Syndrome. NH4Cl (0.10 - 10 mM) had no effect on astrocyte volume regulation or ATP concentration. Salicylate significantly reduced ATP concentrations at 3.0 mM and 10 mM but had no effect on volume regulation. Hexanoate (10 mM and 30 mM) decreased astrocyte ATP content by over 80% while octanoate (10 mM) reduced ATP content by more than 50%. Concentrations of these fatty acids at or below 3.0 mM had no effect on ATP content. Volume regulation was inhibited by 3.0 mM hexanoate and 3.0 mM octanoate but not lower concentrations. Dodecanoate (0.1-3.0 mM) decreased cellular ATP content by 33-51% in iso-osmotic PBS solutions. Phosphocreatine content was reduced by exposure to salicylate or octanoate at concentrations which had no effect on ATP content. These results indicate that astrocyte energy metabolism and volume regulation may be compromised by agents associated with cerebral edema in Reye's Syndrome. Analysis of the dose-dependence of these effects suggests that inhibition of astrocyte energy metabolism is not sufficient to affect volume regulation. PMID- 1294869 TI - Effects of variations in the duration of diffusible-tracer infusions on calculated values of global and local cerebral blood flow. AB - Using dual tracer quantitative digital autoradiography and iodoantipyrine (IAP), we compared local cerebral blood flow (LCBF) measurements using two different infusion times within the same animal. Rats were given concurrent infusions of 14C-IAP and 123I-IAP; one tracer was administered over 20 seconds and the other over 40 seconds. Pairs of autoradiograms, one representing predominantly 123I and the other 14C, were then produced from 20 micron-thick brain sections and images from each section were digitized and processed to produce pairs of digital images of LCBF. The corresponding LCBF images were compared quantitatively on a pixel-by pixel basis. Global LCBF values were greater (28%) at 20 seconds compared to 40 seconds, consistent with the previously reported "falling flow" phenomenon. Perhaps more importantly, the actual pattern of LCBF differed in certain regions such as the cortex, hippocampus, thalamus, and cerebellum between the two time points. In other words, the quantitative patterns of calculated LCBF values were dependent upon the duration of tracer infusion, even when the infusion times were kept below recommended limits (45 seconds). Thus, errors in LCBF measurements may occur in certain structures even in brief experiments. Because these errors are spatially dependent rather than blood flow dependent, there is presently no model which can be globally applied to the brain to correct them. PMID- 1294871 TI - [Tubular sclerosis]. AB - Tubular sclerosis is a pulp-dentin complex defensive response to several physiologic and pathologic stimuli; it leads to an increasing tubular obliteration which enormously reduces dentinal permeability. Its typical structural features are either increased peritubular dentin thickness or "caries crystals". Pathogenesis is a much debated question: some authors assert that peritubular dentin thickening is the main liable for sclerosis while others support a centrifugal theory. Another point of view considers its pathogenesis the result of many integrated mechanism. PMID- 1294870 TI - [Immunological phenomena in pulpal-periapical lesions]. AB - Based on an extensive review of the literature, the authors examine immunological reactions in pulpal and periapical lesions. Although it has been known for some time that bacterial infection causes this pathology, attention has been recently focused on immunological factors in the ambit of the phlogistic process. The present study examines the correlation between the latter and the type of extent of antigenic response, focusing attention on their important role in the phenomena of osteoclastic activation and inhibition of bone repair. From a physiological point of view there are few inflammatory cells in dental pulp, like macrophages and T lymphocytes. When the pulp comes into contact with the antigenic substance it activates a specific and aspecific immune response: the form through the activation of B and T lymphocytes, and the latter through the action of LPS, PMN and complement. An important role in the immune response is played by the cytokines which are able to regulate the intensity and duration of the immune response against potential pathogenic agents. It was initially thought that these were only produced by lymphocytes and as a result they were known as lymphokines. Later it was observed that other cell populations were also able to produce them. Phlogosis of the periapex starts before the pulp is fully necrotic. Tissue detritus and products of bacterial derivation escape through the numerous endoparadontal communication pathways and stimulate an inflammatory response by the vascular system of the parodontal ligament. The concomitant immune reaction occurs due to the tendency to block and restrict the inflammation to the radicular channels, thus preventing its diffusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294872 TI - [The clinical and microbiological evaluation of the efficacy of oral irrigation on the periodontal tissues of patients wearing fixed orthodontic appliances]. AB - The aim of the present study has been the evaluation of the effectiveness of oral irrigation with or without toothbrushing and dental flossing, in individuals treated with fixed orthodontic appliances, on controlling the development of dental plaque and, hence, of gingivitis. Eight individuals with a good general and oral status have been chosen. Before the experimental period, they received instructions about oral hygiene with toothbrushing and dental flossing and then they have been monitored to verify they were doing well. At the time T0, the upper tooth have been banded, three Periodontal Indexes (Plaque Index according to Silness and Loe, Modified Gingival Index according to Lobene and Gingival Bleeding Index according to Ainamo and Bay) registered and subgingival plaque samples from the premolars' gingival sulcus collected in order to point out the total anaerobes bacterial counts, the rates of motile bacteria, spirochetes, Gram positive and Gram negative cocci and bacteria, by means of optical and dark field microscopy and of cultural methods. For their oral hygiene, the patients had to use, in the right side toothbrush and dental floss (Control 1), in the left side the oral irrigator alone (Test 1). One month later (time T1), the lower teeth have been banded, too. In the right side the patients had to use toothbrush and dental floss (Control 2), while in the left one they used the same devices as Control 2 plus the oral irrigator (Test 2). At the time T1 Periodontal Indexes and Microbiological analyses have been extended to all the four quadrants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294873 TI - [Oral symptoms in the climacteric. A prevalence study]. AB - The female climacteric is attributed to physiological ovarian failure with the consequent decrease in the secretions of oestrogen, progestones and androgens. Numerous metabolic, psychological and physical changes have been associated with this event. Oral discomfort, including the burning mouth syndrome and the dry mouth syndrome, has been described as a menopausal symptom. However, the relationship between the hormonal changes related to climacteric and the onset of oral discomfort is still controversial. The purpose of the present study was to evaluate the prevalence of oral symptoms, with particular regard to burning sensation, xerostomia, altered taste and recurrent oral ulcerations. The relationship between oral and climacteric symptoms and psychological status of the patients was also evaluated. A questionnaire was administered to 136 women (mean age: 51.2 years, range 40-62) being consecutively referred to the University Hospital Menopause Clinic from October 1991 to March 1992. The questionnaire included informations regarding menopausal state, oral symptoms, drug assumption, wearing of partial or total dentures, parafunctions (lip and cheek biting, bruxism, tongue thrusting). Climacteric symptoms including flushes/sweats, palpitations, headache, arthralgia/myalgia, vaginal dryness, decreased concentration, tiredness, decreased libido, insomnia, vertigo were evaluated. Visual analogue scale (VAS) was used where appropriate. Information regarding the alteration of the psychological status was collected by means of the Hospital Anxiety and Depression Scale Statistical analysis was performed by chi 2 test or Fisher's Exact Probability Test and Mann-Whitney U-test. The level of significance accepted was 5%. The subjects in this study were divided into two groups on the basis of their answers to the questionnaire: group I (no. 39), premenopausal women; group II (no. 97), menopausal women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294874 TI - [An update on nonsurgical periodontal therapy. A review of the literature]. AB - In this review the authors examine the currently accepted nonsurgical treatment modalities, the role of pharmacotherapeutics in the prevention and treatment of periodontal disease and in the maintenance of the results. They also consider the utility of nonsurgical treatment for cases of advanced periodontal disease and the future direction of clinical practice and research. PMID- 1294875 TI - [Lipoma of the parotid gland. Comments on a case]. AB - The authors present a case of parotid gland lipoma. They underline the clinical features, the unusual finding of it in the parotid lodge and the relationship with the surrounding tissues. After having shown the nosologic pattern of this neoplasm they underline the importance of the instrumental investigations by means of ET, TC and RM, that lead to a nearly sure pre-surgery diagnosis. PMID- 1294876 TI - [Mucopolysaccharidosis. A case report of Morquio's type-A disease (MPS IV-A)]. AB - The mucopolysaccharidosis represent a broad spectrum of disorders due to the deficiency of one of a group of enzymes which degrade three classes of mucopolysaccharides: heparan sulfate, dermatan-sulfate and keratan sulfate. The general phenotype includes coarse facies, corneal clouding, hepatosplenomegaly, joint stiffness, hernias, dysostosis multiplex, mucopolysaccharides excretion in the urine and metachromatic staining in peripheral leukocytes and bone marrow. Various components of the MPS phenotype are also found in the mucolipidoses, glycoprotein storage diseases. Detailed clinical and radiologic evaluation and identification of the type of MPS excreted in the urine help to narrow the diagnosis possibilities. Definitive diagnosis requires assay of specific enzymes in various tissues such as cultured skin fibroblasts. For the moment there are 14 types of known mucopolysaccharidoses, including several subtypes. They are classified into Hurler's syndrome (MPS I-H); Scheie's syndrome (MPS I-S); Hurler Scheie's syndrome (MPS I-H/S); Hunter's syndrome A, B (MPS II-A, B); Sanfilippo's syndrome A,B,C,D (MPS II-A,B,C,D); Morquio's syndrome A,B,C (MSP IV-A,B,C); Maroteaux-Lamy's syndrome (MPS VI) and Sly's syndrome MPS VII). The mucopolysaccharidosis incidence is around 0.04-0.3% of the newborn and they are 1.5% of all congenital disorders. All mucopolysaccharidosis are autosomal recessive disorders, except for Hunter's syndrome that is X-linked and recessive. Patient suffering of MPS, usually, don't show clinical sign from their birth in fact they develop later their characteristics. The average surviving of this patients is around 20-30 years old, and the exitus is due to cardiac failure or to infections to the gastrointestinal tract or to instability of atlantoaxial joint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294877 TI - [Hypertrophy of the masseter: a rare case associated with hypertrophic cardiomyopathy]. AB - Masseteric hypertrophy is a rare, monolateral or bilateral lesion. The aetiology is often unknown and both congenital and acquired forms are reported in the literature. The authors report a case of masseteric hypertrophy associated with hypertrophic cardiomyopathy. Family history shows two brothers suffering from the same cardiac disease. Echography, computed tomography, EMG test and aspiration biopsy of masseteric muscle were performed. Echocardiography and HLA, B and C antigens of 16 relatives were also performed. In the report case the authors hypothesized a multifactorial background on a genetic basis. PMID- 1294878 TI - Nutrition in inflammatory bowel disease. PMID- 1294879 TI - Nutrition support in inflammatory bowel disease. AB - Many patients with the inflammatory bowel diseases, Crohn's disease, or ulcerative colitis have significant protein-calorie malnutrition and micronutrient deficiencies. Factors that contribute to these nutritional deficits include inadequate nutrient intake, malabsorption, excessive nutrient secretion across the diseased gastrointestinal tract, drug-nutrient interactions, and increased nutrient requirements. In this review, the use of enteral and parenteral nutrition support as primary therapy for active Crohn's disease and ulcerative colitis is discussed. Other roles for nutrition support in patients with inflammatory bowel disease, including preoperative nutrition support, nutritional treatment of intestinal fistulas and growth retardation, and home parenteral nutrition for gut failure, are also reviewed. PMID- 1294880 TI - Standards for home nutrition support. American Society for Parenteral and Enteral Nutrition. PMID- 1294881 TI - Home hyperalimentation for inflammatory bowel disease. AB - Total parenteral nutrition (TPN) has become a useful tool in the management of patients with inflammatory bowel disease (IBD). In the past, it was felt that TPN would have a therapeutic role in IBD, but experience has shown that it functions more as an adjunct to other therapeutic interventions. The specific roles of TPN in IBD include: (1) nutritional maintenance in the short bowel syndrome, (2) TPN as adjunctive therapy in jejunoileitis of Crohn's disease, (3) home TPN (HTPN) in Crohn's colitis, and (4) preoperative repletion of significantly depleted patients going to surgery. The adaptation of hospital techniques to the home situation has allowed patients to carry out long-term TPN therapy at home. Patients with IBD on HTPN are subject to the same mechanical and metabolic problems as are other patients on HTPN and, in addition, have a higher infection rate. When carried out appropriately, however, HTPN is a valuable technique in the management of patients with IBD and may provide an improved quality of life. PMID- 1294882 TI - Ten-year survival of a Broviac catheter. AB - We report a patient with regional enteritis and short bowel syndrome who has been treated with home parenteral nutrition for 19 years, during 10 of which he used a single Broviac central venous catheter. The catheter finally required replacement because of progressive lumen occlusion, which was presumed to be caused by thrombosis. At the time of replacement, the catheter was found to be friable and embedded in a hard sheath that made it adherent to the wall of the internal jugular vein and prevented complete removal. At some time during the ensuing 16 months, the retained fragment embolized asymptomatically to the pulmonary artery. During the first 2 months after the placement of a new Hickman catheter, progressive flow resistance developed, probably because of calcium phosphate precipitation, although no change had been made in the parenteral formulation. It resolved immediately upon the instillation of hydrochloric acid into the catheter. PMID- 1294884 TI - A.S.P.E.N. moves to stop USP chapter on medical foods. PMID- 1294883 TI - Glutamine content of whole proteins: implications for enteral formulas. AB - In two recent clinical trials in surgical patients, supplementation of total parenteral nutrition with daily doses of 12 or 20 g of glutamine resulted in a diminished loss of free glutamine in skeletal muscle tissue. Studies in animals exploring the use of both enteral and parenteral glutamine supplementation suggest that glutamine may be an essential nutrient in the maintenance of gut structure and function during critical illness. These findings have led to heightened interest in the glutamine content of enteral formulas. This article describes a method for estimating the glutamine content of whole-protein enteral formulas. The average amount of glutamine in selected, whole-protein formulas ranges from a minimum of 3.55 g/4200 kJ to a maximum of 5.15 g/4200 kJ. Although it is still too early to define the safest and most effective dose of glutamine, there are two points regarding glutamine supplementation that clearly merit further investigation: no clinical trials have been conducted to assess the potential benefits of glutamine supplementation of an enteral diet or to assess the effects of using diets containing protein-bound glutamine rather than free glutamine. PMID- 1294885 TI - Use of lipids in enteral and parenteral nutrition. PMID- 1294886 TI - Selenium deficiency in long-term total parenteral nutrition. AB - Although selenium is an essential trace element, it is often not routinely added to total parenteral nutrition (TPN) formulations. When selenium is not added, patients are at risk for selenium deficiency. This report describes such a patient. He had several operations for colon cancer, including a massive resection of the small bowel that resulted in a short bowel and a fistula. TPN was started after his last operation. After he was discharged, he had a normal, active lifestyle, except that he limited oral intake to water and an occasional soft drink. After 3 years of almost exclusive nourishment by TPN, he developed whitened nail beds. Investigation for possible trace element deficiency resulted in a finding that he had very low levels of selenium in his blood. He did not have any of the cardiac or skeletal muscle abnormalities that have been associated with selenium deficiency. After supplementation with selenium, his blood levels of selenium rose and the nail bed changes were reversed. PMID- 1294887 TI - The essential fatty acids. AB - In animal and human tissues, there are four families of fatty acids that are derived from the precursors palmitoleic, oleic, linoleic, and linolenic acids. Of these, linoleic and linolenic acids are essential dietary elements for humans and all higher animals. The four precursor fatty acids are metabolized (through desaturation and chain elongation) to form the long-chain polyunsaturated fatty acids. The principal fatty acids derived from linoleic acid are arachidonic acid, which contains four double bonds (tetraene) and dihomogamma linolenic acid, whereas products formed from linolenic acid are eicosapentaenoic acid and docosahexaenoic acid. The major products from palmitoleic and oleic acids are the 20 carbon fatty acids with three double bonds (triene). In the presence of adequate dietary amounts of essential fatty acids, tetraene products predominate in plasma. When the intakes of both linoleic and linolenic acids are low, triene formation is high and hence the triene/tetraene ratio in plasma is used to assess the index of essential fatty acid deficiency. The polyunsaturated fatty acids derived from essential fatty acids serve as cellular membrane phospholipid components which can influence the physicochemical characteristics of the lipid bilayer. Changes in membrane lipids can modify the mobility and function of a variety of membrane proteins which may result in altered cell/organ functions. Linoleic acid is specifically required in the skin to maintain the integrity of epidermal water barrier. The dihomogamma linolenic acid, arachidonic acid, and eicosapentaenoic acid are the precursors of eicosanoids which influence many cell processes and organ functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294888 TI - Intravenous fat emulsions in clinical practice. AB - The use of intravenous fat emulsions has become an integral part of the provision of parenteral nutrition. In the past, this was achieved by the administration of lipids separately from the dextrose-amino acid base solution. More recently, lipids have been admixed along with the dextrose-amino acid formula as a total nutrient admixture (TNA). This article discusses the advantages and disadvantages of TNAs, the factors that affect the stability of emulsions, the potential for microbial growth in TNAs, and guidelines for the compounding of TNAs. PMID- 1294889 TI - Glutamine content of whole proteins: implications for enteral formulas. PMID- 1294890 TI - Lithium treatment and memory assessment: methodology. AB - Clinical observations have suggested that lithium may exert adverse effects on memory. The difficulty in achieving empirical consensus regarding this issue has reflected several methodological problems: diversity of research designs, heterogeneous samples, lack of control groups and the possible confounding of memory test scores by variables such as depression, other acute psychopathologies, organicity, treatment duration, and age. The diversity of memory tests in terms of the complexity and modality of the stimuli as well as the types of memory assessed (immediate, short- and long-term, logical, visuo practic) has further complicated the comparison of results across studies. Furthermore, the administration of test batteries has been limited by patients' fatigue and the severity of their illness, and by the time required to complete testing. Hence, the use of test norms may be restricted. Suggestions are made for the selection of appropriate memory tests, patients sampling and data analysis. The authors discuss the difficulties inherent in blind studies and in matched group designs examining the effects of lithium on memory. Conclusions point to the advantages of prospective within-subject designs with repeated testing in which patients serve as their own controls. PMID- 1294891 TI - Widespread reduction of regional cerebral blood flow during hyperventilation induced EEG slowing ('buildup'). Observation from subtraction of brain imaging with single photon emission computed tomography using technetium-99m hexamethyl propyleneamine oxime. AB - To study the pathophysiological mechanisms of hyperventilation-induced EEG showing, i.e., the so-called 'buildup' phenomenon, changes in regional cerebral blood flow (rCBF) were investigated before and during the phenomenon in a 16-year old woman with headache, thought to be of neurotic origin, by subtraction technique of brain images with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime (99mTc-HMPAO). The tracer uptake during buildup decreased by 31-42% as compared to baseline values at rest before buildup in all of the measured regions, reflecting a widespread reduction in rCBF. Gas analyses of arterial blood collected during buildup showed a decrease in PaCO2, and increases in PaO2 and pH with a slight decrease in blood pressure and an increase in pulse rate. These results directly demonstrate a close correlation between the hyperventilation-induced EEG and rCBF changes, suggesting that the buildup phenomenon results from cerebral ischemic change, presumably due to cerebral vasoconstriction caused by the PaCO2 decrease. PMID- 1294892 TI - EEG and evoked potentials in episodic-dyscontrol syndrome. AB - The neurophysiologic correlates of explosive rage and violence are uncertain and controversial. We recorded 17-channel electroencephalograms (EEGs), brainstem auditory-evoked potentials (BAEPs), and long-latency auditory-event-related potentials (AEPs) in 23 patients with impulsive, aggressive and violent behavior satisfying criteria for episodic-dyscontrol syndrome. Most patients also satisfied criteria for intermittent explosive disorder, although some had had conduct disorders in childhood or had previously used psychoactive substances. Sixteen of 23 patients had normal EEGs, while 7 had diffuse or focal slowing not ascribable to drowsiness or the effects of medication. They differed significantly from 20 age-matched patients with headaches, of whom 1 had an abnormal EEG (chi 2 = 4.68, p < 0.05), and from 24 depressed patients, all of whose EEGs were normal (chi 2 = 4.83, p < 0.05). Patients and normal control subjects did not differ in BAEP latencies. N100 and P160 AEP amplitudes were lower in episodic-dyscontrol patients than in control, but the difference was not significant. These findings suggest that non-specific cerebral dysfunction and EEG changes may be associated with disordered impulse or behavior control. Episodic dyscontrol may be associated with other evidence of minimal brain dysfunction. PMID- 1294893 TI - Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits. AB - Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity. PMID- 1294894 TI - Cognition and vigilance: differential effects of diazepam and buspirone on memory and psychomotor performance. AB - Effects of a single dose of the anxiolytic buspirone (15 mg) on memory and psychomotor performance were studied in healthy volunteers and compared to those of the classic benzodiazepine anxiolytic diazepam (15 mg). The study was performed in a double-blind, placebo-controlled way. Three groups of 12 subjects were exposed to an extended test battery before and after intake of drug or placebo. Next to this, an evaluation session took place 1 week later. Immediately after intake, diazepam exerted major effects on memory, impaired psychomotor performance and decreased alertness. In particular, long-term memory had deteriorated, which was interpreted as anterograde amnesia. One week later, more items were recalled from the predrug session compared to the number of items from the postdrug session; this was interpreted as retrograde facilitation. After intake of buspirone, there were no effects of alertness and vigilance, on psychomotor performance and on memory. One week later, a small memory decrement was noticed for verbal material, which was considered as a sign of anterograde amnesia. These results indicate that effects of anxiolytics on memory can be more easily demonstrated 1 week later than immediately after drug intake and, furthermore, that the disruptive effects of diazepam outweight the small effects of buspirone. Finally, it was established that the effects of diazepam on cognition might be mediated by its effects on alertness and vigilance and that cognitive effects are not related to the anxiolytic properties of the drug. PMID- 1294895 TI - Are there EEG correlates of mental states in animals? AB - The thesis of this paper emerges from the fact that mental states are generated by neural processes that also produce an associated electroencephalogram (EEG). Thus, it is logical to expect correlations between mental state and EEG. The corollary is that the EEG can serve as an index of mental state, which can be particularly useful for studies in animals, where mental states are much less accessible for objective study than in humans. Herein, I briefly review the traditional approaches that have informed our attitudes about animal mental states. Virtually all of our conclusions about mental states in animals are drawn by inference from behavioral observation, a process that is highly and unavoidably subject to anthropomorphism. Traditionally, the electroencephalogram (EEG) has been used in a crude way as an objective indication of physical and behavioral state in animals. This, however, has led to substantial controversy, because there are several situations in which EEG patterns and behavior seem to be dissociated. We not only fail to understand these dissociated states, but there are also important humane animal-welfare issues that remain unresolved because we do not fully understand the extent to which the EEG can reflect mental state. At issue is whether EEG-behavioral dissociations, to the extent that they exist, are proof that the EEG is dissociated from mental states. Powerful new EEG methods, such as topographical EEG mapping, wavelet analysis, and testing for nonlinear ('chaotic') dynamical properties and short-term serial dependencies, are now available for studying the extent to which the EEG can index thinking and feeling in humans and, by extrapolation, in animals. Critics who have become disenchanted with the utility of the EEG should at least concede that fresh approaches to old problems are now available and should therefore be thoughtfully considered. If such research does nothing more than improve the rigor of the debate over animal welfare and rights issues, it will be worth the effort. PMID- 1294896 TI - Intensity dependence of auditory evoked N1/P2 component and personality. AB - The slope of the amplitude/stimulus intensity function (ASF) of sensory evoked potentials was found to be related to 'action-oriented' personality traits like 'sensation seeking', 'extraversion', and 'impulsivity'. We studied the ASF slope of the auditory evoked N1/P2 component as well as short-term ASF slope changes and their relationship to a German personality inventory (Freiburger Personlichkeits-Inventar) in 33 healthy subjects. The ASF slope correlated negatively with 'life contentment' and positively with 'stress' in the first run. Stronger associations, however, were noted between slope changes within one test session and personality. Subjects scoring high on the second-order factor 'aggressive excitability' were characterized by a slope decrease from the first to the second run, following a 20-min interval. This finding of personality dependent test-retest changes of the ASF slope stresses the importance of monitoring the duration of the recording when studying ASF slopes and offers an explanation for inconsistencies in the literature concerning cross-modal correlations in visual and auditory ASF slopes. The hypothesis is proposed that the serotonergic system, which has been related to 'action-oriented' personality, is involved in the modulation of the intensity dependence of the auditory evoked N1/P2 component. PMID- 1294897 TI - [Normovolemic induced hemodilution. Behavior of various hemodynamic indices]. AB - Changes in mixed venous oxygen saturation of hemoglobin (SvO2), heart rate (HR), cardiac index, (SI) were measured in 20 patients undergoing major orthopedic surgery (rachis and pelvis bone resections for tumours: mean-lasting 8 hours), to estimate the safety limits during isovolemic hemodilution. Up to Hb 8 g%, in all patients, a cardiac index improvement (+41%) was found, and this was mainly caused by an increase in stroke index (+31%). For 16 patients at Hb 6 g%, this improvement was present only in 44% and declined during further hemodilution. In all cases, CI was moderately lower than baseline value (-18%) this was caused by an important increase in HR (= 55%) partially compensating for by the fall in SI (-57%). The Authors conclude that, in patients under general anaesthesia, isovolemic hemodilution is safe up to Hb 8 g%. Below this value the left ventricular performance rapidly declines. PMID- 1294898 TI - [Rationale for anesthesia in non-cardiac surgery on patients with heart transplant]. AB - The introduction of cyclosporine in the prevention of rejection, together with the improvement of surgical and anaesthetic techniques, produced a tangible increase in long term survival time and the life quality of heart-transplanted patients, so that, they have to undergo non-cardiac surgical operation, more and more frequently. The aim of this report is to analyse the essential physio pathological, clinical, haemodynamic and pharmacological knowledge in order to perform a safe anaesthesia on the above mentioned patients. The Authors are basing this report on experience obtained in deep study of their own cases. In fact they have anaesthetized 190 patients during heart transplantation; later on, 27 of these patients have undergone subsequent major or minor non-cardiac surgical operations. PMID- 1294899 TI - [Anesthesia and central nervous system in carotid surgery]. AB - The Authors, in the debate concerning the most appropriate anesthesiologic treatment in thromboendarterectomy surgery, relate their experience using three different types of general anaesthesia under electroencephalographic monitoring. The results are commented correlating data with some physiopathologic considerations. Carotid surgery, in particular the operation of thromboendarterectomy (TEA), during the last few years has assumed features and frequency typical of a routine procedure. Nevertheless, if from a surgical point of view the criteria of choice of the patients and the surgical techniques have been well standardized, in the anesthesiologic field the discussion between the supporters of the locoregional anaesthesia on one side and of the general anaesthesia on the other side is still open. By this report we mean to bring a contribution to the debate correlating our anesthesiologic files with some physiopathologic notations on the theme. PMID- 1294900 TI - [Gastric tonometry. Experience of a polyvalent intensive care unit]. AB - Tonomitor NG tube was positioned in the stomach of 11 critical ill patients during their stay in ICU and 48 measurements of intramucosal pH (pHi) have been performed. In 7 patients haemodynamic measurement were performed in concomitance with each pHi measure. The Authors looked for statistical relations between pHi and SAPS, pHa, HCO3-a, MAP, DO2/BSA, VO2/BSA, SvO2, diuresis and outcome. A good correlation was found between pHi and MAP (r = 0.47). Dividing the considered parameters into 2 groups in agreement with pHi values < or = and > 7.32 significant relations (p < 0.05) results between pHi and SAPS, MAP, pHa. More significant relations were found between pHi and outcome (p = 0.0015) and between the mean of the pHi values obtained from each patient (pHi-m) and outcome (p = 0.0005). The pHi-m of the surviving patients was always > 7.32 while the pHi-m of the deceased patients was always < 7.32. This results confirm the importance of the pHi measured during the stay in ICU as a prognostic index and suggest that the MAP may be the most important haemodynamic parameter which correlate with pHi values. PMID- 1294901 TI - [Anesthesia and perioperative care in radical cystectomy]. AB - The results of anesthesia and perioperative assistance on a series of 84 patients who underwent since 1982 to 1990 a one-stage radical cystectomy and urinary diversion are reported. Reduction of the high risk of operation is particularly dependent on preoperative preparation, use of a safe anesthesia technique with continuous evaluation of vital signs, control of blood loss and use of low dose of heparin for prevention of venous thromboembolism. The complication rate was low, 7.1% for the early one, 16.6% for late one. General mortality of 5.9% is dependent on the high average age of the patients and on the fact all the cases were deeply invasive cancer. PMID- 1294902 TI - [Aspiration syndrome in cesarean section. Our experience from 1980 to 1990]. AB - In the last twenty years maternal mortality attributed to anaesthesia has decreased. Inhalation of gastric contents is the commonest cause in patients undergoing cesarean section; in fact pregnant women are considered "high risk" because of gravidic modifications. In this retrospective study of 10017 caesarean sections performed under general anaesthesia in our institution between January 1980 and December 1990, we evaluated the frequency of this syndrome (7 cases = 1:1431). We had no case of maternal and neonatal mortality. All these seven patients were admitted at our recovery room for less than 5 days; aspiration pneumonitis occurred in only three patients. Our results suggested that induction of anaesthesia with high doses of thiopental reduces complications related to light anaesthesia, including vomiting. At a dose of 5-6 mg/kg thiopental didn't produce any significant neonatal depression as documented by Apgar scores. PMID- 1294903 TI - [Treatment and outcome of prospective organ donors in neurosurgical intensive therapy. Analysis of a 3-year period]. AB - Strict guidelines for selection, monitoring and treatment of Potential Organ Donors (POD) in Neurosurgical Intensive Care Units (ICUs) are mandatory since patients with Acute Brain Injuries (ABI) are more frequently admitted on these specialized ICUs. We report the guidelines accepted in the Neurosurgical ICU of Treviso City Hospital (TVH) and the results obtained in the last three years (1988-1990). All patients with unfavourable neurological outcome were considered POD if absolute or relative contraindications to organ procurement were absent. They were treated with a multisystemic approach, according to standard protocols, including: ECG monitoring, water and electrolyte balance restoration, pharmacological cardiocirculatory support, prophylaxis and treatment of infections, control of hormonal disturbances. Our data demonstrate an increase of POD from TVH due to the centralization of patients with ABI in the Neurosurgical ICU and show an increase of the rate of POD from Neurosurgical ICU vs General ICU of TVH. The increase of POD in the Neurosurgical ICUs involves medical, legal, organizing and psychological problems, related to this clinical condition. The attention to severe protocols, that must be periodically reviewed, makes more easy the management of POD and ameliorates the outcome of these patients. PMID- 1294904 TI - [Brachial plexus block by the axillary route. Cannulation of the neurovascular sheath with a G22 spinal needle. Our experience with 100 cases]. AB - The aim of this study was to evaluate the utility of the brachial plexus block using an axillary route employing the technique in which the needle is inserted into the sheath at an angle parallel to the neuro-vascular bundle with a sole modification: using a G22 spinal needle and without evoking paresthesia. The results obtained show that this method ensures an improved and more widespread analgesia. The flexibility and small size of the G22 spinal needle allow traumas to the axillary guaina and brachial plexus to be reduced to a minimum. In addition its length enables the anesthetic solution to be diffused around the first rib, including the axillary and musculo-cutaneous nerves, thus ensuring e total sensory and motor block of the upper limb. PMID- 1294905 TI - [Postoperative pain in shoulder surgery]. AB - Postoperative shoulder pain should be adequately treated not only because of the high severity of the symptomatology often observed, but also because pain and muscle contraction render impossible an early rehabilitation programme. Regional anaesthesia, by virtue of its beneficial effects on the pathophysiology of pain and its influence on the rehabilitative problems of shoulder surgery, is the most adequate technique for the control of postoperative pain. PMID- 1294906 TI - [Ambulatory anesthesia in arthroscopy of the knee: proposal of an intravenous general anesthesia technique]. AB - The Authors propose a technique completely i.v. for arthroscopy of the knee by means of proposal discontinuous infusion. The advantage underlined are tolerability, efficaciousness, features of awakening and a few collateral effects verified, and this leads to be conclusion that this anaesthesia system must be considered of choice in this type of surgery. PMID- 1294908 TI - [Urapidil and dopamine in severe heart failure. A clinical case]. AB - The Authors report their experience with a new vasodilator drug (Urapidil) employed in the management of serious cardiac failure, in a patient who previously didn't respond in a satisfactory manner to a therapy with Dopamine alone. After several days of continuous treatment, the patient was discharged, without any sign of toxic or metabolic reactions. PMID- 1294907 TI - [Brain death and prolonged fetal survival]. AB - The Authors presents in detail a case of a 25-year-old primigravida that had fatal intracranial bleeding at the beginning of the 15th week of gestation, whose vital function are sustained for 49 days. Despite the insuccess to bring the pregnancy to a gestational period favorable to induce the delivery, they analyse the problems connected to the maternal maintenance and to the fetal growth. PMID- 1294909 TI - [Subarachnoid anesthesia and peridural anesthesia: which are the causes of total failure? A clinical case]. AB - The paper reports the case of patient undergoing cystoscopy and subsequently radical cystectomy suffering from BPCO and pulmonary emphysema who received sub arachnoid anesthesia during the first operation and peridural anesthesia during the second, with total failure both times. The techniques were correctly performed and on both occasions it was necessary to resort to general anesthesia in order to perform the operation. PMID- 1294910 TI - [Case report: application of peridural stimulation in a case of intractable coccygodynia]. AB - The Authors report a case of coccygodynia following a car accident and describe the therapeutic approach used. In view of the clinical characteristics of pain and the limited quality and duration of benefits, it was proposed to insert an epidural neurostimulation electrode in an attempt to normalise the threshold of neuronal activity at the level of the spine. PMID- 1294911 TI - [How to write a scientific paper]. PMID- 1294913 TI - [National survey on the action taken at the intensive care units to control hospital infections]. AB - In 1990, a survey of recommended infection control practices in ICUs was carried out in 11 European countries. At the European level, 1005 ICUs returned the questionnaire (response rate = 61.2%), while in Italy only 129 ICUs out of 289 answered (response rate = 45%). The survey showed that the diffusion of recommended infection control practices in Italian ICUs was similar to other European countries, even if infection control resources at the hospital level were scarce: a hospital infection control program was launched ad necessary resources were available in only 14% of the responding Italian ICUs. PMID- 1294912 TI - [Chronic exposure to inhalation anesthetics and immunity]. AB - The existence of a professional disease caused by exposure to general anesthetics has been reported by a number of studies, but opinions still differ as to the effective implications of this type of exposure. The aim of the present study was to analyse alterations in cellular and humoral immunity in anesthetists regularly exposed to general anesthetics. Regression analysis showed that IgA and NK lymphocytes were significantly increased whereas total T lymphocytes reduced in parallel with age and length of service. It can therefore be supposed that the increase in IgA might suggest chronic liver disease, while alterations in the lymphocyte populations, even if closely associated to chronic exposure leading to the hypothesis of a cause-and-effect relationship, do not alter immune system functions since they are similar to those that occur with ageing. PMID- 1294914 TI - [Multicenter study on the treatment and outcome of patients admitted to intensive care units in Italy. Presentation of the research project and the study protocol. GiViTI (Gruppo Italiano per la Valutazione degli interventi in Terapia Intensiva)]. AB - Although Intensive Care Units (ICU) are present in most of the Italian Hospitals for acute patients, the heterogeneity of the patients case-mix and the large variation in structural, organizational and staffing arrangements have limited the feasibility and precision of evaluation studies aimed at assessing the quality of health care delivered and its impact on patients outcomes. To our knowledge there has been no nationwide study aimed at assessing the quality and effectiveness of the delivered care in samples of ICUs and patients that are representative of the source populations. To study the effects of variations in health care practices on the outcome of the patients admitted in ICU, we designed a multicentric observational study involving 120 ICUs within the country. The present study is the first part of a project involving a network of Intensive Care Units gathered under the name of GiViTI-Italian Group for the Evaluation of the Interventions in Intensive Care-that is representative of the national Italian reality in the field. The idea of a large collaborative group acting in the field of Intensive Care stands in line with several quality, effectiveness and resource utilization studies that are ongoing in other European countries and is also the result of a series of smaller-scale experiences carried out by other Italian groups eventually emboied in the GiViTI project. In the framework of the ongoing long term, multisite, and multidisciplinary project, the present study calls for the recruitment of all consecutive patients seen at the participant centers during a two months period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294915 TI - [The type of coma as prognostic indicator in severe cranial trauma in childhood]. AB - Various methods are used by neurologists to evaluate posttraumatic brain damage. The most important and reliable are the length of posttraumatic amnesia and coma. In previous papers we have already described the value of the type of coma in the prognosis of serious head injury in childhood (Baracchini-Muratorio et al. 1985; Pruneti et al. 1985). In this study, 30 children (aged 6-12 years) with serious closed head injury and subsequent coma were evaluated. The children were divided into two groups according to the type of coma, using the Plum and Posner coma classification (1966) modified by Pagni et al. (1974). The children were followed up for at least two years (9 for five years) after the trauma by means of neurological, physical, EEG, CT scan and neuropsychological examinations. The neuropsychological test results confirm the hypothesis of a different evolution of sequelae in relation to the type of coma, independently of length of coma and site of brain damage. PMID- 1294916 TI - [Transcranial Doppler for the monitoring of gas embolism in neurosurgical operations in the sitting position]. AB - The risk of venous air embolism is significant in neurosurgical procedures performed in the sitting position. Monitoring for venous air embolism, therefore, is crucial and can be approached from several aspects. The most sensitive generally applicable clinical method for the detection of intracardiac gas is based on an application of the Doppler principle. The Authors describe the technique used to adapt a transcranial Doppler (TC 2-64 B, EME, Germany), and a probe designed to record the Doppler signal from intracranial arteries (Transcran FP 2, EME, Germany), as precordial Doppler in order to monitor venous air embolism in neurosurgical procedures performed in the sitting position. PMID- 1294918 TI - [Fentanyl prevents the pain at the site of propofol injection]. AB - The effect of fentanyl, administered immediately before propofol, when pain is experienced at the site of propofol injection was studied in 28 children undergoing elective surgery. The intravenous administration of fentanyl (2 micrograms/kg) significantly reduced such pain compared with a control group receiving saline. The results suggest that the administration of fentanyl may be a valid procedure in relieving pain on injection of propofol. PMID- 1294917 TI - [Blood levels of cortisol and prolactin. Are they indices of the degree of protection against surgical stress?]. AB - The paper evaluates the level of analgesic protection by assaying cortisol and prolactin levels in two groups of 20 patients each undergoing general anesthesia using two different techniques: TIVA with propofol and fentanyl, and BPN-nitrous oxide. The results showed that TIVA caused a very slight increase in residue cortisol which was, however, within normal limits. With BPN-nitrous oxide anesthesia there was a greater increase in cortisol, reaching a statistically significant level in blood collected one hour after the end of surgery. With regard to prolactin, there was a marked increase in this hormone using both techniques although in percentage terms this increase was lower in TIVA. These results show that plasma prolactin is a more sensitive test than cortisol assay in evaluating antalgic protection and that, of the two anesthetic techniques used, the most protective appears to be TIVA with propofol and fentanyl. PMID- 1294919 TI - Postoperative pain control by transdermal fentanyl. Preliminary comparison of two dosages to a fixed-interval i.m. morphine regimen. AB - The efficacy of postoperative pain control with two doses of transdermal fentanyl were compared to a fixed-interval intramuscular (i.m.) morphine regimen in 21 patients undergoing orthopedic surgical procedures. The two transdermal fentanyl patches with delivery rates of 70-80 micrograms/hr and 90-100 micrograms/hr, groups one and two, respectively, were compared to an i.m. morphine regimen of 150 micrograms/kg every 6h, group three. Transdermal patches were applied one hour prior to surgery and removed after 24h. Analgesia, safety scores, side effects, and a global postoperative evaluation were recorded by a blinded physician at frequent intervals up to 36h. No significant difference in pain intensity, evaluated by the visual analog scale, were found between the three groups. Group two had the lowest discomfort score. Groups one and two had a significantly lower respiratory rate than group three. Although there were isolated significant differences in peripheral hemoglobin saturations, these differences were not consistent. This is the first study in which transdermal fentanyl was compared to a fixed-interval i.m. morphine protocol without supplementation with other narcotics. The results show that fentanyl by a transdermal route can provide analgesia comparable to i.m. morphine. No clinically important adverse side effects were found in any of the study groups. PMID- 1294920 TI - [TOSS (time oriented score system): definition of the nurse/patient relations based on the timing of the workload. Validation during the stay. Gruppo Italiano Multicentrico di Ricerche in Terapia Intensiva (GIRTI)]. AB - TOSS, together with severity of illness (SAPS) and intensity of processes (TISS), has been determined in 941 patients on the 9th day of ICU stay, to ascertain the validity of TOSS in the calculation of the nurse/patient ratio, not only at the time of admission to ICU but also during the stay. The mean values of all indexes measured on day 9 proved lower than those measured on day 1. When the patient population were divided into survivors and non survivors, the above finding held true for surviving patients, while only TISS showed such behavior in patients who eventually died. On the contrary, both TOSS and SAPS on day 9 were not significantly different from those on day 1. Moreover, overall TOSS and TISS were linearly correlated on both occasions; however, the slope of regression lines were significantly different for the two measurements. Specifically, TOSS grew less rapidly, as a function of TISS, on day 1 compared to day 9; this yields, at equal TOSS value, a lower TISS value on day 9 compared to day 1. Therefore, TOSS demonstrates to be a suitable index to determine the nurse/patient ratio, more reliable and straightforward to be measured than TISS. PMID- 1294921 TI - [Systemic poisoning caused by percutaneous absorption of mineral spirit]. AB - Owing to a car accident, the clothes of a injured joiner were permeated with a timber impregnating product containing 51.8% of mineral spirit (a mixture of naphthenes, aromatic and aliphatic hydrocarbons). Despite a short-lasting skin exposure (approximately 40 minutes), dermal contact has caused full thickness burns that, in their turn, have made easier the percutaneous absorption and the storage of organic solvents in subcutaneous tissue depots. Twenty-four hours later, clinical findings of neurologic involvement have arisen, that have got worse when the peripheral tissue perfusion has got better by the adequate replacement of lost blood. PMID- 1294922 TI - [A rare case of "secondary" drowning]. AB - The Authors present a case of a young man who drowned in sea water after the shock caused by a lightening that fell close to him as the swam. The Authors discuss and analyze the effects of the two events (drowning and lightening) which developed similar cerebral injuries but with a different origin. PMID- 1294923 TI - [Post-anesthesia rhabdomyolysis syndrome following muscular stress. 2 case reports]. AB - Effort rhabdomyolysis is a syndrome which takes the form of a pathology with different etiopathogenetic stages. General anesthesia may trigger off acute muscular cytolysis which is probably influenced by the inflammatory surgical pathology itself. The observation of two cases of post-anesthetic rhabdomyolysis following muscular stress suggest that the exhaustion of muscle energy reserves and the consequent alteration of the ATP/ADP ratio may act as a trigger mechanism for this syndrome. Its close relationship with malignant hyperthermia makes a precise anamnesis vitally important, especially in relation to recent intense physical effort in patients undergoing emergency surgery for acute pathologies. PMID- 1294924 TI - [A task force on AIDS]. PMID- 1294925 TI - [Processing, targeting and import into the mitochondria and peroxisomes of proteins coded by nuclear genes]. AB - I have herein discussed two gene-enzyme families in maize whose protein products participate to purge toxic oxidants from cells, and are thus of importance to all aerobic organisms. We have demonstrated that plant mitochondria import precursor proteins (i.e., preSOD-3) in a manner analogous to other eukaryotic cells. The "transit peptide" (TP) of preSOD-3 is 31 amino acid long and has similar properties to other reported TPs for mitochondrial and chloroplastic proteins. Import to peroxisomes is uniquely different from that for mitochondria and chloroplasts in that no consensus presequence seems to be involved. Instead, targeting signals seem to be integral parts of peroxisomal proteins. PMID- 1294926 TI - [A comparative analysis of notochord formation in amphibian embryos]. AB - We studied the origin, structure, and development of the notochord in Pleurodeles waltlii (Urodela) and Xenopus laevis (Anura) embryos. The notochord rudiment is formed in both species at the early gastrula stage as a cluster of polarized chorda-mesoderm cells located along the sagittal plane of the embryo. In Pl. waltlii the notochord rudiment is separated from the gastrocoele roof as a result of contraction of apical cell surfaces. The contraction wave spreads forward and backward along craniocaudal axis, i.e., segregation of the notochord rudiment progresses in two directions simultaneously. Similar process takes place in X. laevis embryos; however, propagation of the contraction wave in the anterior part of the body somewhat differs from that in the posterior part. While the "anterior" contraction wave resembles that in Pl. waltlii embryos, progression of the wave in the posterior part of the body is distinguished by a closer association of the notochord rudiment with ectoderm and the presence of its delamination boundaries with the somite mesoderm. PMID- 1294928 TI - [The effect of the micromanipulations used for transgenosis on mouse development]. AB - Non-specific effects of micromanipulation techniques used for producing transgenic mice on processes of embryonic development were studied. Zygotes obtained from C57BL and BALBxDD mice were treated as follows: (1) incubated in culture medium; (2) the male pronucleus punctured with a glass microneedle; (3) microinjected with a buffer solution; and (4) DNA (mouse P-35 oncogene with human insulin gene promoter) injected into the male pronucleus. Then zygotes were transferred into oviducts of syngeneic or allogeneic pseudopregnant females. Such treatment resulted in the intrauterine death of embryos, as well as in birth of the dead or non-viable offspring with numerous defects of development. Zygote pronucleus puncturing is the most damaging manipulation, since its effect exceeds that of the zygote incubation and is comparable with the effect of buffer of DNA injections. PMID- 1294927 TI - [Cytological study of the nucleolus organizer regions in the chromosomes of CBA and C57BL mice and their hybrids]. AB - Transcriptionally active NORs of chromosomes visualized by AgNO3 staining were studied in bone marrow and embryos (day 10 of gestation) of CBA and C57BL mice, as well as of (CBA x C57BL)F1 hybrids. These mouse strains were shown to differ by the average number of Ag-positive NORs in marrow cells; in hybrids, the number of NORs is greater than in the parent strains. During embryogenesis, the number of chromosomes carrying silver-stained NORs increases; however, no significant differences by this parameter was detected between hybrid and C57BL embryos. The average number of silver-stained NORs was the smallest in embryos of CBA mice. PMID- 1294929 TI - [Oocyte maturation and activation in the common frog and the clawed toad under the action of divalent cations]. AB - Maturation of Rana temporaria and Xenopus laevis oocytes was induced by solutions containing Mn2+ and Co2+ ions. Completion of oocyte maturation was estimated by the following criteria: (1) appearance of the maturation promoting factor (MPF) in the oocyte cytoplasm and (2) oocyte capacity to activation and formation of male pronuclei from the injected sperm nuclei. X. laevis oocytes matured under the effect of Co2+ ions were shown to contain MPF. Oocytes of both species matured under the effect of either ions could not be activated by pricking with a needle and injected sperm nuclei didn't transform into pronuclei. R. temporaria oocytes matured under the effect of ions in late spring, when natural spawning takes place, showed spontaneous activation. PMID- 1294930 TI - [Parthenogenetic activation of bovine oocytes maturing in vitro]. AB - The effect of hyaluronidase (0.3%) and killed bull spermatozoa on the parthenogenetic activation of cow oocytes matured in vitro until metaphase II was studied. It is shown that hyaluronidase, killed spermatozoa, and both agents in combination activate 3.4, 15.0 and 29.6% oocytes, respectively. PMID- 1294932 TI - [Phenogenetic analysis of independent and dependent differentiation]. PMID- 1294931 TI - [The centriolar cycle in polykaryons containing prematurely condensed chromosomes or telophase-like nuclei]. AB - In fused interphase-mitotic cells, either interphase nuclei are induced to premature chromosome condensation (PCC) or mitotic chromosomes are induced to telophase-like nuclei (TLN) formation. This study concerns structural and functional changes in centrioles of fused cells in which PCC or TLN are induced. Embryonic pig kidney cells were fused using a modified PEG-DMSO-serum method. Cell cycle period of the nuclei was determined before cell fusion using double labeling autoradiography. Polykaryons containing desirable type of PCC or interphase nuclear combination in TLN were selected on the basis of isotope labeling after being embedded in epon. Selected cells were cut into serial sections and studied under electron microscope. The data obtained showed that centrioles at every interphase period undergo mitotic activation when their nuclei are induced to PCC. They acquire fibrillar halo and form half-spindles. Daughter centrioles at G1, S and G2 periods are also capable of mitotic activation when separated from their mother centriole. Inert centrioles were found in some cells with G1-PCC. When mitotic nuclei are induced to TLN formation, their centrioles also become inactivated. They lose fibrillar halo and mitotic spindles break down. Some mitotic centrioles develop features characteristic of interphase period such as satellites and vacuoles. Induced nuclear and centriolar changes are simultaneous and may be controlled by the same factor. Mitotic factor of mitotic cell partner which induces PCC may also induce interphase centrioles to mitotic activation. Degradation of the mitotic factor leading to TLN formation may also cause the loss of the mitotic activity of centrioles and disorganization of mitotic spindles. PMID- 1294933 TI - Pathomorphologic atlas for differential diagnosis of skin diseases, with particular regard to tumors. Part II. Neoplasms and pseudo-neoplastic proliferations. PMID- 1294934 TI - [Secondary prevention of colon cancer]. AB - Each year more than 6000 patients in Poland die from cancer of the colon. Morbidity due to colonic cancer increases rapidly in our country. From 1973 to 1982 there was a three-fold increase in the morbidity due to colonic cancer as compared to the years 1952-1955. Five-year relative survival in the same periods did not improve, either being 28% in men and 27% in women. To compare, in the USA with high morbidity rates due to colonic cancer where each year there are 145,000 new cases of cancer, 5-year relative survival is 42% for men and 54% for women. This raises a question whether our strategy of treatment of colonic cancer is correct. This question is even more justified now when secondary prevention of colonic cancer is of practical value. Total mortality due to colonic cancer is 60%. However, diagnosis and treatment of early forms of colonic cancer reduces mortality to 20% and below. Therefore, effective management colonic cancer should include not only the so-called primary prevention (interfering with etiological factors for instance through high fibers diet) but also secondary prevention through monitoring of precancerous changes in the colon, removal of potentially malignant lesions and early forms of colonic cancer [19]. Secondary prevention interfering with the pathogenesis of colonic cancer is the subject of the present paper. We would like to emphasize the need for a better management program for colonic cancer, especially that the data concerning colonic cancer in Poland may be underestimated due to diagnostic neglect and faulty cancer register.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1294935 TI - Colorectal carcinoma as a genetic phenomenon. AB - Carcinogenesis in human large intestine is a result of multiple, heterogeneous and random genetic changes. Deletion of tumor suppressor genes and activation of oncogenes appear to be important molecular events. These compromise the loss of chromosomes 5, 17, 18 or functional inactivation of FAP, p53 and DCC genes. Activation of Ki-ras and c-myc oncogenes seems to be crucial for both cell immortalization and morphology modification. Identification of genes involved in this process enables both a screening and a new classification. Also it is an important step towards a gene therapy. PMID- 1294936 TI - Colorectal polyps in autopsy material. Part I. Adenomatous polyps. AB - In prospective studies specimens of the large bowel were obtained from 733 autopsy cases. After fixing they were examined under illuminated magnifying lens and all polypous lesions were excised for histological analysis and classified according to Correa's criteria (8). Adenomatous polyps were found in 280 cases (38.2%) and their prevalence increased with age in both sexes. Adenomatous polyps, also multiple were found most frequently in the transverse colon, and then ascending colon, sigmoid, descending colon and rectum. The mean number of adenomatous polyps per positive specimen was 2.33 for men and 2.60 for women. In 6.8% their diameter was > or = 10 mm. The prevalence of polyps with severe degree of dysplasia (III degree) increased from proximal to distal segments of the colon in both sexes and their prevalence is significantly higher in the ascending colon in women. In the whole series there were 6 adenocarcinomas of 5-18 mm in size, all in women over 80 years of age. The results of the present study were compared with the data concerning other populations of the world. In the light of a repeatedly confirmed a generally accepted relationship between adenoma and adenocarcinoma of the large intestine the results of our study seem to underestimate the prevalence of colon adenocarcinoma in the population of Cracow and Cracow district. PMID- 1294937 TI - Current methods in histopathology. AB - The past decade has presented many new methods to histopathology. However, there are important reasons for establishing these methods in every institute for pathology. It is not enough just to exchange old equipment into new systems. It takes a careful judgement what will be the benefits from a new system for the institute, the hospital and the patient. Important factors like institute management, quality assurance, quality control, speed, competitiveness, profitability and environmental safety aspects are high ranking tasks in the modern institute of pathology, next to the specialization in new diagnostic areas like immunohistochemistry, bone-pathology (bone-morphometry/undecalcifield iliac crest biopsy histology), flow cytometry, image analyzing or PCR-techniques etc. The main target of each institute of pathology, weather of private nature or a governmental/state institution, is the establishment of a high quality, safe and reliable diagnosis in the fastest time and for a price based on a standardized, accepted and economical system. Institutions will be more controlled by certain economical departments which have to watch the cost-/profit situation of the hospital and it's individual institutions in comparison to the average country standard and the average European standard. The introduced methods are mostly standard in "Western" institutes. However, it is of utmost importance that the institutes in "Eastern Europe" establish these standards as soon as possible in order to be competitive and to be able to join research-projects with "Western" universities - a necessary source of income. PMID- 1294938 TI - Pharmacokinetic and pharmacodynamic significance of antidepressant drug metabolites. PMID- 1294939 TI - Mode of action of fibrates. AB - Fibrates are a class of hypolipidaemic drugs that effectively reduce plasma triglyceride and cholesterol levels, but also raise HDL cholesterol. In recent years the attention of pharmacologists and clinicians to fibrates has been renewed also in the light of a multifaceted action on plasma lipids as well as on factors modulating the thrombotic homeostasis in blood. The mechanisms of actions underlying these effects are discussed in this short review. PMID- 1294940 TI - Vasoactive eicosanoids in the rat heart: clues to a contributory role of cardiac thromboxane to post-ischaemic hyperaemia. AB - To assess the potential role of vasoactive cardiac eicosanoids in the modulation of coronary flow, we measure thromboxane(TX)B2, 6-keto-prostaglandin(PG)F1 alpha, PGE2 and sulphido-peptide leukotrienes (LTC4, D4, E4) in the coronary effluent of isolated perfused rat heart in both baseline and post-ischaemic conditions. Leukotrienes were undetectable. The order of production rate for the other eicosanoids was 6-keto-PGF1 alpha > TXB2 > PGE2. Production of such substances was increased about seven-fold over control after 5 min. global ischaemia; experiments with hypoxia showed that this was due to an actual increase in synthesis and not to a washout effect. A platelet source for TXB2 was excluded by 111In platelet labelling experiments. We assessed relative sensitivity to inhibition of cardiac TX synthesis relative to production of 6-keto-PGF1 alpha to inhibition by aspirin, ibuprofen, diclofenac and the specific thromboxane synthase inhibitor OKY-046. Aspirin, ibuprofen and diclofenac decreased 6-keto PGF1 alpha production at a concentration always greater than required for a similar extent of TX inhibition. On the other hand a selective inhibition (> 90%) of TX was observed in the presence of OKY-046. Regression analysis of various 6 keto-PGF1 alpha/TXB2 ratios, as obtained in these different conditions, vs coronary flow, showed no correlation in baseline conditions, but a significant positive correlation (r = 0.59, P < 0.01) for post-ischaemic values. These data suggest a role for cardiac eicosanoids, including a non-platelet, cardiac-derived TX, in modulating the hyperaemic response in the isolated rat heart. PMID- 1294941 TI - Effects of a beta 2-agonist (clenbuterol) on cultured human (CG-5) breast cancer cells. AB - In order to gain further knowledge about the possible oestrogen-like activities of clenbuterol (a beta 2-adrenergic drug illegally used as partitioning agent in food producing animals), we treated a hormone dependent human breast cancer cell line (CG-5) with different concentrations of the drug (10(-3) M to 10(-8) M). The effects of clenbuterol and oestradiol on cell proliferation were compared. Both oestradiol and clenbuterol, at low concentrations (10(-7) M and 10(-8) M) stimulated cell proliferation, but the effects of clenbuterol were less marked and significant. Probably clenbuterol elicited cell proliferation through a different mechanism, since it did not affect the cellular oestrogen receptor concentration. Clenbuterol failed in binding to the high affinity oestrogen receptors present in the CG-5 cells. As the beta-adrenergic receptors and the susceptibility to their stimulation have been recently demonstrated in vivo and in vitro in many tumour and normal cells, it is reasonable to suppose that clenbuterol may induce cell proliferation through beta-adrenergic stimulation. PMID- 1294942 TI - Effects of sulglycotide on endogenous prostaglandin synthesis in human antral mucosa. AB - The effect of sulglycotide, a polysulphated glycopeptide isolated from pig duodenum, on PGE2, 6-ketoPGF1 alpha and TxB2 production from isolated biopsy specimens of human antral mucosa was investigated in vitro, in comparison with carbenoxolone. In addition to a tendency toward increased PGE2 production just short of statistical significance, both sulglycotide and carbenoxolone significantly increased 6-ketoPGF1 alpha accumulation in the incubation medium. TxB2 levels were not significantly modified by the two drugs. Therefore, changes in the prostanoid production by human antral mucosa could, at least partially account for the cytoprotective effects of sulglycotide in man. PMID- 1294943 TI - [Recent advances in xenotransplantation]. AB - Interest in xenotransplantation has dramatically increased in the past 4 years, focusing on the potential use as donors of distantly related animals such as pigs (discordant xenografts). The major barrier is hyperacute rejection. The mechanisms responsible for this rejection include: specific reaction of the recipient's natural antibodies with antigens in the donor's organ, direct activation of the recipient's complement system by endothelial cells in the donor's organ, and/or relative failure of complement inhibitory proteins in the donor's organ to impede activation of the recipient's complement system. In case of vascularized xenograft, the temporary depletion of anti-donor antibodies (anti ABH or anti-HLA class I) from a graft recipient may allow the long term survival of the graft despite a possible return of the antibodies to the circulation. This phenomenon is called accommodation. The mechanisms involved could be: the endothelial cells in a graft develop a resistance to complement mediated injury; the antigens expressed on the blood vessels become modulated or changed; the natural antibody repertoire changes in such a way that there are fewer anti-donor antibodies. The accommodation phenomenon encourages the view that the barrier to xenotransplantation is not immutable. PMID- 1294944 TI - [Residual lymphocytes after specific depletion. Functional study]. AB - We previously demonstrated that, following a 2-day stimulation of T cells by MHC incompatible cells, a ricin A-chain conjugated to a monoclonal anti-IL2 receptor p55 subunit can kill 1.5 log of the activated alloreactive T cells while non specific killing of alloreactive T cells of a third partner does not exceed 0.5 log. This methodology is of potential use for selective alloreactive T cell depletion in MHC incompatible bone marrow transplantation in order to prevent both graft versus host disease and graft rejection. This study shows that this T cell depletion method does not alter T cell reactivity to microorganism antigens encountered in infection following BMT. It was found that T cell proliferation to cytomegalovirus and to candida antigens is not affected as shown in proliferative assays and by limiting dilution analysis for the latter antigen. PMID- 1294945 TI - [Discordant heart xenografts. Experimental study in pigs conditioned by total lymphoid irradiation and cyclosporine A]. AB - The use of discordant xenografts may solve some of donor shortage problems. The beneficial effects of treatment with total lymphoid irradiation (TLI) and classical drugs on this discordant model of transplantation rejection was evaluated. Twenty-four lamb hearts were transplanted heterotopically in the abdomen of 24 pigs. Group I received no treatment (control). Group II received continuous intravenous medical treatment cyclosporin A (CyA) (5 mg/kg) and azathioprine (3 mg/kg) 3 days prior to transplantation. Group III received the same medical treatment and simultaneously 12 grays of irradiation in 5 equal fractions with a high rate (100 cGy/min) or a low rate (1.6 cGy/min) prior to transplantation. Group IV also received 12 grays in 5 fractions at a high rate followed by the medical treatment started 5 days after TLI and continued until the day of transplantation. Antibody and serum cyclosporine levels were monitored. Histology specimen were analyzed at the end of the experiment. Mean GST (graft survival time) in group I and II was 140 +/- 35 min and 117 +/- 27.4 min respectively. The histological features of these hearts suggested acute humoral rejection (hemorrhage, thrombosis, and edema) without cellular infiltration. In group III, one heart functioned 4.5 days with pathological features of cellular rejection and a second animal died at 6 hours with a functioning graft with no evidence of an acute rejection. Both had been treated with the low rate TLI protocol (1.6 cGy/min). The mean GST in this group was 1080 +/- 794 min. In Group IV, one graft functioned for 6.5 days and another for 3.25 days. Mean GST was significantly increased in this group to 4800 +/- 2647 min (p < 0.05). A cellular infiltration was seen in this two grafts. The remaining graft was rejected in 6 hours with histological lesions typical of acute humoral rejection. Antibodies levels at the time of transplantation were lowest (40%) in group IV and in the low rate irradiation group. The ability of TLI to induce tolerance and to prolong survival in a discordant xenograft model depends upon cumulative dose, rate of irradiation, delay between TLI and graft placement, and combined treatment with immunosuppressive drugs. A high rate of TLI and graft placement is delayed. Low rates of irradiation may be beneficial when there is a very short period between treatment and transplantation. These findings highlight the potential usefulness of TLI in combination with immunosuppressive drug therapy when antibody-mediated rejection occurs, such as with xenograft and in sensitized patient. PMID- 1294947 TI - [T clones, a means of exploring minor antigens involved in graft versus host reaction]. AB - During MHC-matched bone marrow transplantation, a graft-versus-host reaction (GVH) mediated by donor T lymphocytes and directed against host minor histocompatibility antigens may be observed. The establishment of T cell clones from GVH mice has enabled us to study minor antigens recognized during the reaction. Most of the T cell clones were Thyl+CD4+CD8-alpha beta+. Four minor, weakly polymorphic antigens, were evidenced; two of those antigens, recognized by CD4+ T cell clones, were implicated in GVH. One CD8+ T cell clone cannot provoke GVH mortality. The two "killer" clones express V beta 18 and V beta 2 TCR gene segments, respectively. PMID- 1294946 TI - [Superacute xenogenic rejection: attempted treatment with anti-idiotypic antibodies]. AB - Heart xenotransplantation in the guinea-pig to rat model, a highly discordant combination, is invariably followed by a hyperacute rejection of the graft. Preformed IgMs were shown to be responsible for the destruction of the graft by stimulating the complement cascade. We tried to inhibit preformed antibodies, before transplantation, by inducing anti-idiotypic antibodies using autologous Fab' mu specific for guinea-pig endothelial cells. This treatment seems to exert a neutralizing effect on xenogeneic hyperimmunization, against guinea-pig endothelial cells but not against preformed anti-guinea-pig antibodies. PMID- 1294948 TI - [Synthesis of collagen in culture of endothelial cells of the human umbilical vein. Effects of cyclosporine A]. AB - Interstitial renal fibrosis and gingival hypertrophy are frequent side-effects of cyclosporin A which have been attributed to a dysfunction of extracellular matrix synthesis. Endothelial cells might participate in the matrix accumulation observed. We studied the effects of increasing concentrations of cyclosporin A on protein synthesis by human umbilical vein endothelial cells. Collagen synthesis decreased significantly to 800 ng/ml in both medium and cell layer. The percentage of hydroxylation of its proline residues decreased significantly as from 400 ng/ml. The main proteins, analysed by SDS-PAGE, were thrombospondin, fibronectin and the alpha 1 and alpha 2 chains of type IV collagen. These fractions did not show any change after 24 hours exposure to 200 ng/ml of cyclosporin A. These results demonstrate an inhibitory effect of cyclosporin A on collagen synthesis by human umbilical vein endothelial cells. Consequently, matrix accumulation by increased collagen synthesis in cyclosporin A treated patient may not be directly related to the drug effect on endothelial cells. PMID- 1294949 TI - [Expression of HLA-DP antigens on normal and leukemic blood cells]. AB - HLA-DP allodeterminant elicit weak cellular and humoral immune responses. This study was undertaken to find out if the low immunogenicity of HLA-DP could be accounted for by a low level of expression on peripheral blood mononuclear cells. Double staining experiments and flow cytometry were performed in 28 healthy individuals, HLA-DP was found to be as expressed as DR and DQ on B lymphocytes. Furthermore, a DP+/DR- lymphocyte sub-population was identified and characterized as freshly activated T lymphocytes. PMID- 1294950 TI - [Natural killer lymphocytes in kidney transplantation]. AB - We conducted a dual study of phenotype and function of natural killer cells (NK) using flow cytometry, this study being applied to renal transplantation. The CD 16 and CD 56 clusters correlated well with NK cytotoxicity, especially for CD 3 lymphocytes, whereas CD 57 should no longer be considered a NK marker. NK activity was determined on K 562 or Daudi cells, either spontaneously or after in vitro activation with r-interleukin 2 (LAK). Cytotoxicity was analyzed after labeling of target cells by carboxyfluoro-diacetate and measured by flow cytometry. We found that in renal transplant recipients NK cells were deficient in numbers and functions and showed that LAK activity was also diminished. Azathioprine appeared to be the main immunosuppressant impairing NK cells. Viral infections increased the numbers and functions of NK cells, whereas during malignancies they remain as low as in uncomplicated recipients. NK cells deficiency might be involved in the high incidence of de novo malignancies in renal transplant recipients. PMID- 1294951 TI - [Immunodeficiency caused by graft versus host reaction. Extra-thymic effect of thymus in restoring immunity]. AB - Cell-mediated immunity in lethally irradiated graft-versus-host mice can be restored after repopulation with syngeneic bone marrow cells and thymus grafting. The thymus is not only required for the maturation of T lymphocytes, but also for the inhibition of a radioresistant mechanism resulting in lymphoid cell rejection. PMID- 1294952 TI - [Routine application of HLA class II oligotyping. Value of automatization]. AB - HLA class II typing by DNA amplification and hybridization with allele-specific oligonucleotides has led to an improvement of the overall typing accuracy. In an attempt to apply this procedure to a large-scale analysis, we sought to implement an automation system using the Biomek 1,000 robotic work-station. This system allows a rapid preparation of many consecutive samples and avoids the risk of human errors. It is now routinely used in several laboratories. PMID- 1294953 TI - [Interleukin 4 increases lymphocytic adhesion to allogenic endothelium through a dependent protein kinase A]. AB - Interleukin 4 and tumor necrosis factor alpha increase endothelial cell adhesiveness for lymphocytes by promoting adhesion molecules synthesis. We have shown that intracellular mechanisms, which transduce IL 4--but not TNF alpha- signal, involve a protein kinase A. PMID- 1294954 TI - [In situ production of interferon gamma and interleukin 6 by infiltrating cells from human kidney allografts in irreversible rejection. Modulation by cytokines]. AB - Using ELISPOT assays, we detected a significant number of cells secreting interferon-gamma and interleukin 6 among 8 irreversibly rejected kidney allografts compared with normal kidneys. Interleukin 2 increases the frequency of interferon-gamma producing cells and interleukin 4 decreases the frequency of both interferon-gamma and interleukin 6 producing cells. PMID- 1294955 TI - [Kidney transplantation in hyperimmunized patients ignoring the cross-match performed with historic sera]. AB - To ignore the positivity of renal pretransplantation cross-match performed with peak sera remains a controversial practice. The present study concerns 11 renal transplantations after positive cross-match with peak sera and negative cross match with current sera. The clinical results of these transplantations lead to the assumption that peak sera contained HLA antibodies not specific to the graft and non HLA antibodies responsible for the positivity of the cross-match. PMID- 1294956 TI - [Polycythemia after kidney transplantation]. AB - Between 1971 and 1990, 251 kidney transplanted patients with a well functioning graft were evaluated to determine the frequency of post-transplant erythrocytosis (PTE). Thirty-one patients (13 percent) developed polycythaemia 10.6 +/- 10 months after transplantation. Thromboembolic complications occurred in 22 percent of the cases. The frequency of PTE was higher in males than in females (sex ratio: 7.2 vs 2.1; P < 0.05). Patients with renal dysplasia had a lower incidence of PTE (3 vs 22 percent; P < 0.05) as did those who had been treated with azathioprine (9.4 vs 19 percent; P < 0.05). None of the patients treated with recombinant erythropoietin before transplantation developed PTE during a mean follow-up of 15.1 +/- 4.5 months. The majority of polycythaemic patients had normal erythropoietin levels. These results show that there is an erythropoietin independent proliferation due to an increased sensitivity of erythroid progenitors or to an erythroid stem cell stimulation by cytokines. PMID- 1294957 TI - [Kinetics of erythropoietin blood levels from D-1 to D-29 in kidney transplantation]. AB - This study of serum erythropoietin levels and reticulocytes counts in the first month after kidney transplantation shows that the erythropoietin peak is efficient only when serum creatinine level at the time of the peak is under 200 mumol/l. PMID- 1294958 TI - [Diagnosis of stenoses of the renal artery graft by pulsed echo Doppler velocimetry. Application to the prospective evaluation of the incidence of stenoses of renal graft artery]. AB - The value of pulsed Doppler velocimetry (PDV) to detect renal graft artery stenosis was evaluated in a prospective study of 42 kidney-transplanted adult patients. The results of PDV were compared with those of arteriography which is regarded as a reference examination. With PDV the diagnostic sensitivity was 85 percent and specificity was 82 percent. The low cost and good sensitivity (provided the interpretation problems are known) of this harmless examination make it a good instrument to detect renal graft artery stenosis. In order to obtain an early diagnosis, 148 kidney-transplanted patients were systematically examined by PDV 1, 3, 6 and 12 months after transplantation. The incidence of renal graft artery stenosis was evaluated at 6.8 percent. PMID- 1294959 TI - [Kidney biopsy puncture, kidney aspiration puncture with fine needle, examination of urine sediment in phase contrast. Comparative study for the diagnosis of acute rejection in kidney transplantation]. AB - The relative importance of renal biopsy and cytological studies (fine needle aspiration biopsy and urine sediment examination by phase contrast) in the diagnosis of acute rejection episode was evaluated in 30 patients who received a kidney transplant. All patients underwent these 3 examinations simultaneously during an acute degradation of graft function. Sensitivity of renal biopsy, fine needle biopsy and urine sediment was 0.86, 0.68, 0.43 respectively. The association of fine needle biopsy and urine sediment examination increased the sensitivity up to 0.73. Renal biopsy is indicated to assess the vascular and glomerular status or in the presence of inconclusive cytological studies. PMID- 1294960 TI - [Effect of pregnancy on renal function after transplantation]. AB - Between 1968 and 1991, 36 pregnancies were reported in 28 patients who had undergone kidney transplantation at the Necker hospital, Paris. Pregnancies with favourable graft outcome were compared with those accompanied by significant deterioration of graft function and requiring haemolysis. The risk factors for renal function deterioration during pregnancy in kidney-transplanted women were found to be an initial nephropathy induced or aggravated by a previous pregnancy, an alteration, even mild, of graft function, hypertension, even controlled by treatment, an HLA mismatch and several episodes of acute graft rejection soon after kidney transplantation. PMID- 1294961 TI - [Non anti-HLA antibodies and early irreversible rejection after kidney transplantation in children]. AB - Despite the absence of anti-HLA antibodies (Ab) about 10 to 20 percent of renal transplants are lost during the first months from rejection. The role of humoral rejection seems more likely than cellular rejection since they do not respond to standard anti-rejection therapy. We studied 37 patients who rejected their graft despite negative T and B lymphocytes cross-match during the first eight months (m: 59 days, range: 2-240) following kidney transplantation. These patients were compared with 57 patients who experienced a favorable outcome. The sera were tested for the presence of Ab against epidermis of a panel of 5 normal skins and against an epithelial-endothelial hybrid cell line (EA hy 926, Dr C.J.S. Edgell), expressing both endothelial and epithelial antigens. Among the 37 patients who rejected theirs grafts, 8 had anti-keratinocytes Ab, 11 had Ab against epithelial endothelial hybrid cell line, 9 were positive for both tests. Among the 8 pts who lost their graft before 25 days, 5 were positive for at least our test. Conversely, 7 among the 57 pts with favorable outcome had Ab: 2 against keratinocytes, 5 against hybrid cell line. These data suggest that non anti-HLA Ab may play a role in graft rejection. Furthermore the detection of such Ab prior to transplantation may predict patients at risk of severe rejection. In such cases, plasma exchanges may be proposed if they develop steroid-resistant rejection. PMID- 1294962 TI - [Study of CD45 isoforms on T CD8 lymphocytes, in the peripheral blood and the graft in patients after kidney transplantation]. AB - We report characterization of CD45 isoforms expressed by CD8+ lymphocytes in peripheral blood and in the graft of 40 kidney transplanted patients who underwent kidney biopsy on the basis of clinical signs suggesting rejection. Standard histological examination of the biopsy fragments and three-color cytofluorimetric analysis of lymphocytes extracted from the same fragments by mechanical and enzymatic treatment were performed simultaneously and compared to the peripheral blood lymphocytes. In 14/40 biopsies where lymphocyte extraction succeeded, the predominant subset was CD8 (CD4/CD8 mean ratio was 0.53). Almost all CD8+ cells were activated: among these CD8+ cells, 55 percent were HLA-DR+, and 68 percent CD45RO+, i.e. of a memory cell type with cytotoxic activity. This situation resembles the in vitro observation made during mitogenic stimulation of lymphocytes by phytohemagglutinin, OKT3 or CML ("culture mixte lymphocytaire"). Beside their evident interest for the diagnosis, these data could be useful for our understanding of the physiopathology of the rejection crisis. PMID- 1294963 TI - [Transplantation for primary hyperoxaluria. Role of oxalate crystal deposits in the occurrence of kidney failure]. AB - We analyzed the records of 3 patients transplanted for end-stage renal failure due to primary hyperoxaluria and evaluated on repeat biopsies the role played by oxalate deposits in the constitution of renal failure after isolated kidney graft, or combined liver and kidney transplantation. Early failure of the renal graft is frequent and often interpreted as the consequence of recurrence because of the presence of oxalate deposits on the graft biopsy. In fact, the decrease in oxalate deposits observed in our 2 cases of combined liver and kidney transplantation despite the progressive renal failure, indicates that crystal deposition is not responsible for the renal lesions. However, we cannot exclude that the oxalate molecule toxicity plays a role in the constitution of the diffuse sclerosis which occurred in these two cases after a primary renal non function, aggravating a hemodynamic process by using cyclosporin. On the other hand, as observed in our isolated kidney graft, renal crystal deposition occurring before the onset of renal failure suggests the true mechanism explaining the slow recurrence of renal oxalosis. PMID- 1294964 TI - ["Monobloc" resection in heart and lung transplantation. Technique and advantages of a new procedure]. AB - Hemostasis is a usual problem in surgical heart and lung recipient removal. Since April 1990, we have been using as surgical technique an "en bloc" removal of heart and lungs in order to reduce postoperative bleeding and cardiopulmonary bypass duration. PMID- 1294965 TI - [Plasma glycosylated residues demonstrated by proton NMR spectroscopy. Value in the detection of heart graft rejection]. AB - In conjunction with biopsy and Doppler studies, we analysed by high resolution proton NMR spectroscopy the blood plasma of 22 heart transplant recipients. There was a significant variation in the glycosylated residues of proteins with the development of acute cardiac rejection. A more extensive study is underway to assess the sensitivity and specificity of this approach for the early diagnosis of acute cardiac rejection. PMID- 1294966 TI - [Criteria for choice of the donor in heart transplantation in adults]. AB - Among 66 consecutive adult heart transplant recipients operated on from January 1988 to October 1991, 11 experimented early graft dysfunction (4 of them died). Mean donor's age was 37.4 +/- 11 years; 9 patients were older than 50 years; 85 percent of donors received dopamine. Were found without any significant influence on early graft function: donor's age, weight mismatch, duration of donor's intensive care, dose of dopamine administered, external cardiac massage and relative hemodynamic instability, and ischemic time. Conversely, a history of chronic alcoholism in the donor is of pejorative significance, which is not without consequences in view of the current scarcity of donors. PMID- 1294967 TI - [Towards an integrated protection of heart grafts]. AB - In an attempt to provide a consistent protection of cardiac allografts during the sequence of events inherent in transplantation procedures, we developed two preservation solutions of which one is used for initial arrest, storage and cardioplegia during graft implantation, whereas the other serves as initial reperfusate. The formulations of these solutions are closely interrelated and their design has integrated the basic principles of organ preservation with those of myocardium-specific metabolism. Based upon experimental studies in the isolated rat heart model, this integrated approach has yielded better functional recoveries than conventional preservation protocols. PMID- 1294968 TI - [Neonatal heart transplantation. First results]. AB - Two 5- and 17-days old neonates with hypoplastic left heart syndrome respectively underwent orthotopic heart transplantation. The donor-recipient weight ratio was +58 percent and +88 percent; ischemic time was 144 and 167 min. The immunosuppressive protocol included thymoglobulin during the induction period and a classical 3-drug therapy, with a rapid tapering off of prednisone over 3 weeks. No infectious complication was observed; each infant experimented one episode of acute rejection, successfully treated with prednisolone. Forty-three months and 10 months later, the 2 children are doing well, with normal renal function and normal growth. No late rejection episode was observed. Heart transplantation in neonates is feasible, the short-term and mid-term results are good. Despite important ethical problems, heart transplantation represents a great hope for neonates with inoperable congenital heart defects. PMID- 1294969 TI - [Enhancement of the quality of hepatic graft by restoration of hepatic glycogen reserves in the donor]. AB - It has been suggested that depletion of donor hepatic glycogen reserves deleteriously affects the resistance of the hepatic graft to ischemic episodes. In this study, performed in the pig model, we showed that it is possible to enhance the quality of the graft at the time of reperfusion by using a method which rapidly restores the donor hepatic glycogen reserves. With the aid of an isolated liver perfusion model, we compared grafts (n = 24) harvested from pigs fed (group N), fasted for 24h (group J), or fasted with a restoration of glycogen reserves (group P). After the grafts were subjected to 8 hours of cold ischemia, the release of alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase in the perfusate increased in group J (P < 0.05 vs group N); the increase was corrected in group P (P < 0.05 vs group J). When the grafts were subjected to 15 minutes warm ischemia prior to the liver harvest, the production of bile was reduced in group J (P < 0.05 vs group N); bile production was reestablished in group P (P < 0.05 vs group J). The clinical application of such a method of donor nutritional conditioning, in the hours which precede organ harvesting, may enhance the quality of the hepatic graft at the time of transplantation. PMID- 1294970 TI - [Double liver-kidney transplantation in the presence of a positive T cross match]. AB - Kidney transplantation, when performed across a positive T lymphocyte cross match, is always followed by the occurrence of a hyperacute rejection. On the other hand, successful hepatic allografts have been reported under these same conditions. Furthermore, clinically and experimentally hepatic allograft has been reported to induce tolerance of other organs from the same donor. Thus, combined liver-kidney transplantation constitutes an ideal application of these immunological events. We report here the case of a sequential liver-kidney transplantation in which liver transplantation performed prior to kidney transplantation with an organ from the same donor induced kidney tolerance despite an initial positive T lymphocyte cross-match. PMID- 1294971 TI - [Transplantation of a segmental small intestine in dogs. Comparison between jejunal graft and ileal graft]. AB - The purpose of this study was to compare heterotopic jejunal and ileal allografts in the dog under cyclosporine A. Fourteen allografts (8 ileal and 6 jejunal) were successfully performed. There was no case of graft-versus-host disease in this series. Six allografts (42.5 percent), 3 jejunal (50 percent) and 3 ileal (37.5 percent), were rejected during the first 3 months (NS). Eight allografts, 5 ileal and 3 jejunal, were tolerated up to 3 months and then removed; 2 ileal and 2 jejunal were normal; 2 ileal and 1 jejunal showed signs of chronic rejection, and 1 ileal signs of advanced rejection. It is concluded that there is no major difference between jejunal and ileal allografts in the dog. PMID- 1294972 TI - [Incidence and clinical expressions of microvascular complications in patients receiving kidney graft and treated with cyclosporine]. AB - Reported cases of HUS/TTP (hemolytic uremic syndrome/thrombotic thrombopenic purpura) with cyclosporin (CsA) are more and more frequent, which led us to evaluate the incidence of microangiopathic process in kidney graft patients. In our first retrospective study we noted 9.4 percent of HUS/TTP among 117 patients. We tried to detect infraclinical hemolytic events prospectively in 40 new patients by systematic measurement of haptoglobin levels after introduction of CsA. The incidence of falls in haptoglobin levels was 25 percent. The immunological context was always noted: rejection crisis in 5 cases, cytomegalovirus infection in 3 cases, isolated markers of lymphocyte-activity in 2 cases. We never found a clinical or infraclinical form of microangiopathic process without a symptomatic or asymptomatic immunological complication. Monitoring haptoglobin levels make it possible to detect early endothelial injuries which could be linked to the future arteriolopathy described with CsA therapy. PMID- 1294973 TI - [Protective effect of verapamil and dopamine against cyclosporine-induced vasoconstriction in isolated glomeruli in rats]. AB - Cyclosporin A (CsA)-induced nephrotoxicity is characterized by dramatic changes in glomerular filtration rate and renal plasma flow, largely limiting the clinical use of this drug. The vasoconstrictive response of CsA could explain, in part, these hemodynamic alterations. The present study compares the area changes in rat-isolated glomeruli incubated with CsA alone or after pre-treatment with verapamil and dopamine. In verapamil-pretreated CsA-intoxicated glomeruli, size decrease was reduced (-1.5 percent at T10, -3.1 percent at T20 and -4.8 percent at T30), when compared with CsA alone (-4.7 percent at T10, -10.1 percent at T20 and -12 percent at T30). The results obtained with dopamine were similar. In conclusion, verapamil and dopamine can be regarded as fair protective agents against CsA-induced vasoconstriction in rat-isolated glomeruli. PMID- 1294974 TI - [Reduction of TNF-alpha release and clinical effects of the first injection of OKT3]. AB - In order to prevent the adverse effects of a first OKT3 injection in renal transplant recipients, we administered polyclonal antilymphocyte globulins (ATG Fresenius, 4 mg/kg/j) for 3 days before OKT3 injection. Compared with a historical group of 5 patients who did not receive ATG pretreatment before OKT3 injection, the patients who were pretreated by ATG had a significantly lower absolute number of circulating lymphocytes before the first OKT3 injection (363 +/- 107 vs 1,230 +/- 80/mm3, P < 0.001), a lower raise in plasma TNF-alpha level 2 hours after OKT3 injection (178 +/- 42 vs 735 +/- 127 pg/ml, P < 0.005) and a significant decrease in frequency and intensity of clinical symptoms, mainly chills, dyspnea, and headaches. However, fever and peak creatinine level were similar in both groups. A 80 percent success rate of crisis treatment was achieved in both groups and there was no increase in infectious complications. In conclusion, pretreatment with ATG induces a lymphocyte depletion, and decreases the amounts of TNF-alpha released as well as the side-effects of a first OKT3 injection. PMID- 1294975 TI - [Role of reactive oxygen species in acute kidney failure]. PMID- 1294976 TI - [Perioperative remote infections in neurosurgery. Role of antibiotic prophylaxis]. AB - We report the results of a randomized, prospective study devised to assess the effectiveness of perioperative cefamandole prophylaxis on the remote infections rate in neurosurgery. Only two kinds of neurosurgical procedures were studied: shunt placement and craniotomy for brain tumour. In the treated patients cefamandole 1.5 g was given one hour before surgery, then repeated twice eight hourly. When the surgical procedure lasted more than three hours cefamandole 1.5 g was administered throughout the operation. No case of local infection was observed in either group, and the percentage of patients with remote infections was the same in both groups. Leucocytosis and temperature were measured during 15 days following the surgical procedure, and there were no differences between the treated and untreated groups in the evolution of these parameters. This study does not suggest that routine perioperative antibiotic prophylaxis is mandatory in neurosurgery. PMID- 1294978 TI - [Colorectal villous tumors. Treatment by electro-resection and laser photocoagulation. 134 cases]. AB - Endoscopic snare resection prior to Nd:YAG laser photocoagulation was used to treat benign colorectal villous adenoma. One hundred and thirty four patients were included in the study: 72 with surgical contraindications, 61 for whom surgical resection appeared to be too drastic and 1 who refused surgery. Treatment sessions were repeated every fifteen days until total tumour destruction was achieved. A carcinoma was detected in biopsy specimens obtained during endoscopic treatment of seven patients. Eight patients were lost to follow up. Treatment results could be analysed in 119 patients. A successful treatment was achieved in 108 patients. Tumour destruction was complete in 85.4 percent of the cases with lesions of at least 4 cm in diameter and in 94.3 percent of the cases with smaller lesions. During the average 101 weeks follow up period, 15.7 percent of the patients with total tumour destruction had recurrence. The risk of recurrence was correlated with the number of initial treatment sessions and previous surgical treatment. It would appear that endoscopic resection prior to Nd:YAG laser photocoagulation is a safe and effective method for the destruction of colorectal villous adenomas. PMID- 1294977 TI - [Cushing syndrome during pregnancy. New diagnostic methods used in 3 cases of adrenal cortex carcinoma]. AB - Cushing's syndrome during pregnancy is most often caused by an adrenal cortical tumour; it is a rare event which bears poor foetal and maternal prognoses. We report 3 cases of adrenal cortex carcinoma diagnosed during pregnancy (after 24, 27 and 28 weeks respectively of amenorrhea) and revealed by local tumoral signs in 2 cases and by pulmonary embolism in the third. Because hair growth was moderate and weight gain as well as high blood pressure had mistakenly been attributed to the pregnant state, these clinical features of hypercortisolism has only lately been related to tumoral secretion. The hypercortisolic state was firmly established by comparing the patients' urinary cortisol levels (677, 941 and 2,167 micrograms/day) and 20-hour salivary cortisol levels (9.9, 15 and 25.3 micrograms/ml) with values obtained in women at the same stage (88 +/- 11.4 micrograms/day and 2.31 +/- 0.25 micrograms/ml). The aetiological diagnosis was made by the finding of a highly increased salivary testosterone levels (50, 34 and 95 pg/ml; normal = 8.6 +/- 4 pg/ml), and by magnetic resonance imaging which showed unilateral adrenal masses of 3, 8 and 20 cm in diameter respectively. These 3 cases illustrate the difficulty of the clinical diagnosis of hypercortisolism during pregnancy. Assessment of the unbound steroids and magnetic resonance imaging are the most useful methods for an early diagnosis, thus preventing the severe complications which may otherwise reveal this rare pathological condition. PMID- 1294979 TI - [Complications of cervical spine manipulation. A case of "locked-in syndrome"]. AB - The current craze for cervical spine manipulation is due to its rapid and even dramatic results and to the ineffectiveness of many treatments prescribed by physicians. Complications of thoracic or lumbar spine manipulation are very rarely reported, but this is not the case with the cervical spine. We present the case of a woman who suffered a severely disabling complication caused by an "osteopathic" manoeuvre. This technique should be rejected as it is dangerous and as harmless methods can be used with good results in common cervicalgia, even if it is very severe. PMID- 1294980 TI - [Glucose transporters. Physiology and physiopathology]. AB - Glucose transport is an important step in the regulation of glucose homeostasis. Two types of transport systems are described: active transport accumulates glucose in specific cells, whereas facilitative transport equilibrates blood glucose and intracellular glucose inside all mammalian cells. At the present time, different levels of facilitative transport regulation are known. Facilitative transport is achieved by 5 different isoforms; each isoform has its own characteristics and is subjected to tissue-specific regulation. Alteration of glucose transporters expression may be involved in a physiopathological situation such as diabetes which is characterized by insulin resistance of peripheral tissues and impaired insulin secretion by beta pancreatic cells. Thus, Glut 2 expression is reduced in the beta cells of diabetic rats. The reduction of Glut 2 expression correlates with, and may contribute to the loss of glucose-stimulated insulin secretion. However, Glut 2 expression in liver remains unaltered. The insulin resistance of peripheral tissues may be explained in adipose tissue by a decrease in Glut 4 expression. In skeletal muscle, Glut 4 expression remains constant whatever the physiological or physiopathological situation. PMID- 1294981 TI - [Early detection of recurrence of ovarian carcinoma by immunoscintigraphy]. PMID- 1294982 TI - [Lung abscess in ventilated patients. Value of CT-guided percutaneous drainage]. PMID- 1294983 TI - [Cholesterol crystal embolization after intravenous thrombolysis by anistreplase for suspected myocardial infarction]. PMID- 1294984 TI - [Are non-steroidal anti-inflammatory agents justified in the treatment of acute otitis media in children?]. PMID- 1294985 TI - [Relationship between skin hyperpigmentation in AIDS and serum alpha-Melanocyte Stimulating Hormone level]. PMID- 1294986 TI - [Treatment of severe idiopathic thrombocytopenic purpura with high doses of methylprednisolone]. PMID- 1294988 TI - [1st Bencard-Symposium. Chances and risks in modern immunotherapy. Rovaniemi, 5-7 March 1992]. PMID- 1294989 TI - [Reform of clinical environment and problems of patients with mental diseases]. PMID- 1294987 TI - [Absence of HIV 1/HTLV I "autochtonous" coinfection in the region of Nice]. PMID- 1294990 TI - [Dealing with patients with mental diseases who committed crimes in England- present status and problems of their accommodation facilities]. PMID- 1294991 TI - [Therapeutic consideration of patients with mental diseases]. PMID- 1294992 TI - [Treatment of patients with mental diseases who compulsorily hospitalized according to the reports of the prosecutors and the chief of rehabilitation center]. PMID- 1294993 TI - [Patients with mental diseases who committed crime and manpower in psychiatry]. PMID- 1294994 TI - [Three problems exists in patients with mental disorders who committed crimes]. PMID- 1294995 TI - [Administrative viewpoint of systematization of mental health, social welfare and clinical therapy]. PMID- 1294996 TI - [Hospitals' viewpoint of systematization of mental health, social welfare and clinical therapy]. PMID- 1294997 TI - [Psychiatric hospitals' viewpoint of systematization of mental health, social welfare and clinical therapy]. PMID- 1294998 TI - [Psychiatric hospitals' viewpoint of rehabilitation of patients with mental diseases--their residential problems and development of group homes]. PMID- 1294999 TI - [Psychiatric clinic's viewpoint of systematization of mental health, social welfare and clinical therapy]. PMID- 1295000 TI - [Clinical genetic viewpoint of concept in atypical mental diseases]. PMID- 1295001 TI - [Concept of atypical psychotic disorders --comparison of International Classification of Diseases 10 and DSM-III]. PMID- 1295002 TI - [Concept of diagnosis of atypical psychotic disorders in Japan and clinical symptoms--results from multicenter studies]. PMID- 1295003 TI - [Ideal type of psychotic disorder and the ranking]. PMID- 1295004 TI - [Molecular mechanisms of aldosterone biosynthesis]. PMID- 1295005 TI - [The structural and functional characterization of P-450.aromatase (estrogen synthetase)]. PMID- 1295006 TI - [Genetic analysis of the toxins produced by Clostridium botulinum]. PMID- 1295007 TI - [Microdetermination methods for deoxyglucose and beta-NGF using NADP and NAD enzymatic cyclings]. PMID- 1295008 TI - [The low-birth-weight newborn. The training of mothers for care at home]. AB - In March 1989 the sub-program for reducing low birth-weight was put into practice. As a response to the application of this subsystem a plan was started at the Northern Maternal Hospital in Santiago de Cuba aimed at training these children's mothers in relation to techniques for caring babies. By means of the sources used some aspects regarding these newborn children were assessed, as well as the achievements of the mothers in the course during their hospitalization. The results showed the effectiveness of this plan, the advantages of its being adopted by nurses and its great social significance. PMID- 1295009 TI - [Urinary sepsis in children and nursing care]. AB - A study was carried out with children who had been hospitalized due to urinary sepsis at the Ciro Redondo General Hospital in Artemisa, during the first quarter of 1990. Nursing cares are pointed out. Of the 149 children admitted during that period, 13 (8.64%) had urinary infection. The most affected age group was that under 1 year. The germ most often found was Escherichia coli. Vesicoureteric reflux was found in 2 infants and the most common manifestation was fever. PMID- 1295010 TI - [The use of the direct method for the diagnosis of Gardnerella vaginalis vaginitis]. AB - A study was carried out on 200 patients divided in two groups of 100, labeled 1 and 2. They underwent vaginal secretion tests by the direct method in order to assess its appropriateness for Gardnerella vaginalis presumptive diagnosis. This study was related with patients' symptoms, such as leukorrhea and fetidity prevailing in Group 1 and lower abdomen pain prevailing in Group 2, as well as the proportions of germs isolated and the association with this symptom for defining the microorganism role in the occurrence of so-called unspecific vaginitis; Group 1 had 100% of positive plates and Group 2 had 55%, who were given adequate treatment for the couple with further confirmation of the results which were effective in 96.7% of the cases. No relation could be seen between IUD and the presence of germ, since it is likely that its existence was not taken into account on inserting IUD. PMID- 1295011 TI - [Pulmonary hemosiderosis: a case report]. AB - A case of pulmonary hemosiderosis was reported at the Eliseo Noel Caamano Pediatric Teaching Hospital in Matanzas City. It was a three-year-old patient, with clinical picture and complementary investigations. A review was made of the literature regarding the disease, which is unusual in children, especially with such a clear cause. Because of its high morbidity and frequent mortality, it will be imperative to carry out early examination and adequate therapy. Emphasis is placed on specific nursing procedures for the management of this disease. PMID- 1295013 TI - [Interrupted process]. PMID- 1295012 TI - [Pregnancy in adolescence]. AB - The goal of this paper is to provide information about pregnancy in adolescents and to influence those people who have to do with the situation of pregnant adolescents and the family and social consequences. The research was carried out at the Dr. Carlos Diez del Ciervo Hospital from 1989 to 1990. It included 1,500 cases and the variables considered were mothers' age, marital status, number of gestations, number of childbirth, residence and initiation of sexual life. The main findings are stated in detail. PMID- 1295014 TI - [Nursing care in psychiatric emergencies]. AB - The emergency psychiatric services implantation in general hospitals, at Sao Paulo City, motivated the authors to write this article. They present some considerations about psychiatric emergencies and the main points in nursing care of the client in a crisis intervention setting. PMID- 1295015 TI - [The estimate of nursing personnel: a study of 2 methods]. AB - This study aimed at analysing two methods for the calculation of nursing personnel (traditional formula and nursing progressive care), from statistics information on the atendly of the University Hospital of UFPB, in order to choose the most adequate method. The obtained results showed the nursing progressive care method as being the most viable one, provided is made a study in terms of hospital beds occupation, nursing hours per type of care and personnel performance. PMID- 1295016 TI - [The policy of human biological reproduction in Brazil]. AB - The author presents some of the historical determinations of the policies of human reproduction in Brazil, placing them among other social policies. She argues that reproductive profile of the social classes depends upon not only the biological reproduction, but also upon the work power. PMID- 1295017 TI - [The feelings and suggestions expressed by colostomy patients who self-irrigate]. AB - The analysis of feelings and suggestions presented by a group of colostomy patients which use a specific method of colostomy self-irrigation showed that it's well accepted by these patients. After the positive results using this method, we obtained 88.14% of the positive feelings answers specially wellbeing, safety and normality and an average of 0.35 suggestions per client. PMID- 1295018 TI - [The problem of body temperature vis-a-vis the nursing procedure: concepts and regulatory mechanisms]. PMID- 1295019 TI - [The intervention of the nurse in diabetic care]. PMID- 1295020 TI - [The mass communication media in diffusing the ideology of human reproduction]. AB - This study was conducted with women assisted at public health units of one municipality of Sao Paulo's metropolitan region. Its objectives were: to verify the mass-media to which they have access and to correlate these findings to these women's social class. It also intended to analysis the permeability of these subjects to the mass-media messages about human reproduction, correlating it to the biological profile presented by such women. PMID- 1295021 TI - [Playing and learning nurse-patient communication]. AB - The author present an educative game to teach nurse-patient communication. The game was tested by graduate students and utilized by the undergraduate students. Those students, judges and the Author considered this game efficient and adequate to the teaching of the topic under study. PMID- 1295022 TI - [Spiritual holism as a theoretical reference for the nurse]. AB - This paper pretend to talk about spiritual holism as a theoretical referential in nursing research includes some aspects of the occidental thinking on health and sickness concepts. Its shows man as having a very complex nature. PMID- 1295023 TI - [The indirect measurement of arterial pressure as a function of cuff width in patients in the immediate preoperative phase, the phase of entry into the operating room and in the postanesthesia phase]. AB - The goal of this study was to compare blood pressure measures using two sizes of cuffs: one standard width (12 cm) and other with correct width that is 0.38 of arm circumference as recommended by American Heart Association. The comparisons were done among surgical patients in mediate perioperative phase, reception area of operation room and postoperative phase during the staying of the patient in the recovery room. The results demonstrated that the arterial blood pressure was hypoestimated by the use of the standard width cuff, reaching values up 30 mmHg in the systolic arterial pressure and 30 mmHg in the diastolic ones. PMID- 1295024 TI - [The development of a model of the nursing record for the follow-up nursing care of parturients]. PMID- 1295025 TI - Administration of narcotics in cancer pain. AB - Cancer pain can be successfully managed with oral or parenteral narcotics in 80% of patients, if those factors that magnify pain perception are also controlled. Pain from any source can be made worse and pain tolerance impaired by depression, regression, intolerance to stress, and/or recurrent withdrawal, all of which require attention and management. Those patients whose cancer pain is still intractable may benefit from a procedure to interrupt pain pathways. Such procedures have become far less common since the introduction of chronic administration of intraspinal narcotics. The subarachnoid route is preferable to the epidural route because it is less likely to result in catheter failure and because much smaller doses can be used, with less systemic effect. In addition, tolerance can be managed more readily by readjustment of dose with the subarachnoid route, and there is no greater incidence of complications. Intraventricular narcotics can be considered in patients whose spinal canal does not allow catheter placement, at approximately 1/10th the spinal dose requirement. PMID- 1295026 TI - Computer-assisted stereotactic biopsy and volumetric resection of thalamic pilocytic astrocytomas. Report of 23 cases. AB - Twenty-three cases of pathologically verified thalamic pilocytic astrocytomas diagnosed at computer-assisted stereotactic biopsy and/or volumetric resection at the Mayo Clinic between January 1985 and October 1990 were reviewed. Computer assisted stereotactic volumetric resection was performed in 19 patients. Postoperative imaging demonstrated no residual contrast-enhancing tumor in 14 patients and a small amount of contrast-enhancing tumor (less than 5% of the original tumor volume) in 5 patients. Biopsy only was performed in 4 patients: 2 with primarily cystic tumors successfully treated with stereotactic instillation of 32P, and 2 patients with stable (nonprogressive) deficits. There was 1 operative death; a patient with tumor extending into the midbrain became comatose and died 10 days after surgery. The remaining 22 patients are alive and well. Computer-assisted stereotactic volumetric resection of thalamic pilocytic astrocytomas can be performed with low morbidity and a favorable long-term prognosis. PMID- 1295027 TI - Computer-assisted stereotactic third ventriculostomy in the management of noncommunicating hydrocephalus. AB - Between January, 1984, and December, 1990, a total of 85 patients have undergone stereotactic third ventriculostomy (TV) at the Mayo Clinic. Sixty-one patients (74%) presented with mass lesions in the region of the posterior third ventricle, aqueduct of Sylvius or fourth ventricle. Twenty-four patients (26%) presented with non-tumoral, adult/adolescent-onset aqueductal stenosis. Follow-up was available for all 85 patients and ranged from 1 to 66 months (mean 25 months). Follow-up revealed initial patency in 84 patients. Eleven patients (13%) ultimately required extracranial shunting for persistent symptomatic hydrocephalus. Two patients underwent revision of their TV. Twenty-seven patients had been previously shunted. Of these, 23 (85%) have remained asymptomatic after TV without the need for further shunting. Stereotactic TV is a safe and effective way of re-establishing normal cerebrospinal fluid flow dynamics in selected cases of obstructive hydrocephalus. PMID- 1295028 TI - Infratentorial stereotactic biopsy. A review of 11 cases. AB - A review of the stereotactic cases performed at the University of Iowa between February, 1985, and December, 1990, yielded 12 infratentorial stereotactic biopsies in 11 patients. A definitive diagnosis was obtained in 9 of 11 patients. One patient required a second biopsy to obtain a diagnosis and 1 yielded cystic fluid only. The pathological diagnosis obtained included 4 high-grade gliomas, 2 undifferentiated adenocarcinomas, 2 low-grade astrocytomas, 1 malignant ependymoma, 1 pontine hematoma and 1 cyst. None of the patients experienced increased neurological deficit following biopsy and there was no mortality. One patient developed postoperative meningitis. We conclude that stereotactic biopsy of infratentorial lesions can be performed safely with a high probability of obtaining a diagnosis. Adequate tissue diagnosis is necessary to direct further therapy. PMID- 1295029 TI - Computer-assisted neurosurgery: simulation and automation. AB - Instrumentation has been developed to automate, accurately guide, and integrate microsurgery laser resection equipment that is used in stereotactic brain surgery. The instrument is a computer-controlled laser-guiding system. The improvement in the accuracy comes from relying on a certain well-referenced three dimensional surgical orientation, and computer-preplanned tumor contours, rather than only the surgeons hand-eye orientation in the operating room. PMID- 1295030 TI - Interstitial hyperthermia of malignant brain tumors by an implant heating system using stereotactic techniques. AB - Interstitial hyperthermia of malignant brain tumors has been produced by a heated ferromagnetic implant with a low Curie point. Induction heating of the implant, which is stereotactically implanted in a tumor, is obtained by eddy currents in a high-frequency magnetic field. Safe, repeated and long-term treatment of 35 cases of malignant brain tumors has been done using this system. The overall response rate was 31.4%, but the rate for metastatic brain tumors, deep-seated gliomas and others were 50.0, 36.8 and 33.3%, respectively. Deep-seated gliomas were more effectively treated than superficial gliomas by combination with radiation therapy. The common pathological finding was a clearly demarcated coagulative necrosis of ellipsoid shape around the implant. PMID- 1295031 TI - Stereotactic microsurgical resection of intracranial tumors using the electromagnetic field focusing system. AB - The intense heat produced at the tip of the electromagnetic field focusing (EFF) probe at its point of contact with tissue can cut and vaporize tissue and coagulate blood vessels. As the probe is shaped like a bayonet and has a diameter of 0.3 mm at its tip, it can be used on deep structures through narrow openings, making it ideal for stereotactic craniotomy. Thirteen stereotactic craniotomy procedures using the EFF system were performed. Locations of the lesions were deep in the cerebrum, cerebellum and in the lateral ventricle. The system proved efficient with reduced blood loss and unobstructed view of deep structures. No complications resulted from the use of the system. PMID- 1295032 TI - Factors predicting successful stereotactic aspiration of colloid cysts. AB - Stereotactic aspiration is a valuable surgical alternative for colloid cysts, but due to cyst heterogeneity, it is not uniformly successful as the sole treatment in all patients. Since 1981, we performed CT-guided stereotactic aspiration as the initial procedure in 25 patients with colloid cysts. We retrospectively reviewed our experience in the first 22 patients and found that preoperative CT imaging studies accurately determined size and predicted cyst viscosity. The preoperative CT appearance of a hypodense or isodense cyst correlated favorably with successful aspiration. Preoperative MRI provided excellent anatomic definition of the cyst and its relationship to other structures, but failed to correlate successful aspiration. Unsuccessful aspiration was related to the high viscosity of the intracystic material or deviation of the cyst away from the aspiration probe. These factors were used prospectively in 3 additional patients to accurately predict success of cyst aspiration. PMID- 1295033 TI - Stereotactic management of midline brain lesions. AB - Eighty-seven patients, aged 10 months to 92 years, with midline brain lesions were treated using stereotactic techniques at our institution between January 1987 and June 1990. A total of 119 stereotactic procedures were performed with no operative mortality. Procedures included 53 biopsies only, 22 endoscopic laser decompressions, 8 stereotactic microsurgical resections, 9 permanent implants of 125I, 12 temporary implants of 125I, 11 cyst aspirations, 2 cystoperitoneal shunts and 2 intracavitary 32P. The morbidity rate was 4.21%. Local anesthesia was used in 106 of the procedures (89%). Accurate diagnosis was achieved in all cases. Image guidance and stereotactic techniques open new frontiers in the diagnostic and therapeutic management of deep-seated midline intraparenchymal lesions. PMID- 1295034 TI - Comparison of the neurochemistry of the endogenous opioid systems in two brainstem pain-processing centers. AB - SCH-32615 is a new enkephalinase inhibitor whose analgesic effects were examined following its stereotactic microinjection into the periaqueductal gray (PAG) and the ventromedial medulla (VMM) regions of the brainstem of the rat. SCH-32615 produced a strong, dose-dependent, naloxone-reversible analgesia to thermal noxious stimuli as measured by the hot plate test (HP; supraspinal analgesia) and the tail flick test (TF; spinal analgesia). The peak analgesic effect was seen within 10 min and remained for 45-60 min. ED50 were for PAG, HP = 10.7 micrograms and TF = 17.3 micrograms, and for VMM, HP = 5.7 micrograms and TF = 7.2 micrograms. Using the irreversible mu receptor antagonist, beta-funaltrexamine, it was found that the endogenous enkephalins in the PAG produce their analgesic effects by acting at only one receptor subtype (the mu receptor) while in the VMM both mu and delta opioid receptors are involved (not through the delta alone as previously believed). PMID- 1295035 TI - Current spectrum of stereotactic irradiation techniques. AB - Our 10-year experience with stereotactic irradiation techniques was evaluated in a series of 709 patients. Stereotactic intracavitary radiation of cystic neoplasms, brachytherapy of malignant glial neoplasms and radiosurgery represent effective and contemporary primary adjuvant or alternative methods to treat a wide variety of brain tumors and vascular malformations. PMID- 1295036 TI - Distribution of [32P]-chromic phosphate colloid in cystic brain tumors. AB - To suppress cyst formation in 42 brain tumors, 32P has been stereotactically instilled in doses calculated to deliver 20,000-40,000 rad to the cyst wall, assuming uniform dispersal of the radioisotope. However, samples of cyst fluid obtained at varying intervals after injection showed lower than expected activity levels, suggesting early 'plating' of 32P. To accommodate this phenomenon, a surface-area-dependent dosimetric calculation is compared with a volume-dependent calculation which assumes uniform dispersal. These two approaches represent lower and upper extremes. It appears that in small cysts there is less difference in the required administered dose, but in larger cysts potentially very large differences exist and caution should be exercised if uniform suspension is assumed. PMID- 1295037 TI - CT-guided stereotactic injection of radionuclide for treatment of brain tumors. AB - The authors report on 40 brain tumor patients treated with CT-guided stereotactic injection of 198Au and 32P. Among the 40 cases were astrocytoma in 23 cases, craniopharyngioma in 9, meningioma in 4, pituitary adenoma in 2, and pinealoma and metastatic carcinoma each in 1 case. The tumors were all located in deep or important areas of the brain which were difficult to deal with by conventional operation. 62 injections of colloidal isotopes were performed, and all were successful. No major adverse effects or complications occurred on follow-up of 6 12 months, 28 patients were improved in their clinical symptoms, and CT scanning showed that the tumor sizes were diminished. The effective rate is 70%. PMID- 1295038 TI - Three-dimensional imaging for brachytherapy planning. AB - A computerized 3-D brachytherapy treatment planning program has been developed which simulates catheter trajectories, radioisotope seed positioning and percentage dosimetry zones about a catheter/seed array in relationship to CT or MRI images. The high activity 125I seed is used in this program. A visual and a non-linear mathematical optimization program will also be described. PMID- 1295039 TI - Permanent iodine-125 implant and external beam radiation therapy for the treatment of malignant brain tumors. AB - Survival data of 114 patients treated for malignant brain tumors with 125I interstitial radiation therapy at Henry Ford Hospital, Detroit, Mich. (1986 1990), are presented. The first 64 patients were treated with temporary 125I implants with a total prescribed dose of 60 Gy at a dose rate of 40 cGy/h. In order to reduce the risk of injury to the surrounding normal tissue associated with high-dose brachytherapy, a new approach was initiated using permanent implants with a lower dose rate; 50 patients were treated after surgical resection with permanent implantation of 125I seeds at a lower dose rate of 4-7 cGy/h, with a total dose of 10,000-12,000 cGy, and concurrent external radiation therapy of 5,000 cGy. The rationale of this protocol was to increase the effectiveness of the low-dose-rate implant by a concurrent 'daily' boost of external radiation, thus inhibiting the proliferation of tumor cells during the protracted low-dose radiation treatment. Survival was compared between groups with permanent and temporary implants in terms of effectiveness in tumor control as well as impact on clinical condition. Low-dose-rate implant with concurrent external radiation therapy seems to offer the best chance for long-term survival without deterioration in the clinical condition. PMID- 1295040 TI - Fractionated stereotactic radiotherapy for intracranial neoplasms. AB - Fractionated stereotactic radiotherapy is a method which attempts to combine the radiobiological advantages offered by dose fractionation with a technique for focal delivery of radiation. At McGill University, fractionated stereotactic radiotherapy is given with a linear accelerator-based dynamic stereotactic radiosurgery unit. The first treatment is given using the stereotactic frame for target localization and head immobilization. Subsequent treatments are given using skin tattoos and laser alignment for target placement within the isocenter of the linear accelerator, and a modified portable halo-ring device is used for skull immobilization. Typically, a marginal dose of 42 Gy was prescribed at the margins of the lesion, divided in 6 fractions and given over a 2-week period. We report the pathological profile and treatment results in a series of 21 patients with a variety of intracranial tumors, treated in this manner between May 1987 and April 1990. Fractionated stereotactic radiotherapy appears to be a worthwhile procedure for the treatment of well-selected patients with intracranial neoplasms. PMID- 1295042 TI - Clinical and technical results from spinal stimulation for chronic pain of diverse pathophysiologies. AB - Spinal stimulation has been indicated for pain of peripheral deafferentation, but not for low-back pain. Technical and clinical records of 241 consecutive spinal stimulator recipients were reviewed, including: peripheral deafferentation pain (n = 44); predominant pain of low back, postlaminectomy (n = 96), and predominant pain of leg(s), postlaminectomy (n = 48). The groups were not statistically different with respect to important clinical features. For the postlaminectomy syndromes, only the technical results correlated significantly with outcome. Spinal stimulation actually yielded results as good for the 'failed back surgery syndrome' as for peripheral deafferentation pain, because newer technical methods were proven to stimulate the low back predictably. PMID- 1295041 TI - Template-guided stereotactic implantation of malignant brain tumors for interstitial thermoradiotherapy. AB - A phase I trial of 25 patients with anaplastic astrocytoma or glioblastoma multiforme is described. Hyperthermia and radiation were delivered stereotactically by means of template-guided interstitial catheters loaded with ferromagnetic wires and then 192Ir seeds. Implant volumes ranged from 15 to 113 ml (mean 54 ml) involving 9-38 catheters (mean 18); parallel catheters used hexagonal spacing of 1.0-1.5 cm. Patient tolerance of these procedures was excellent. Postoperative morbidity due to additional mass effect or edema was low, but there has been one death and one complication of hydrocephalus, bleeding and symptomatic pneumocephalus, each. PMID- 1295043 TI - Stereotactic mesencephalotomy for pain relief. A plea for stereotactic surgery. AB - Rostral mesencephalic reticulotomy (RMR) for pain relief was performed in 34 patients with intractable pain. Most of these patients have been followed for a long period of time postoperatively, the longest follow-up period being 11 years. Contrary to the commonly prevailed bias in the past that mesencephalotomy may be a surgical intervention with potential risk, these patients of RMR have continued to substantial improvement postoperatively in terms of their preoperative intractable painful dysesthesia after a long period of time. The results of pain relief for denervation pain as well as for nondenervation pain are surprisingly good even after unilateral procedures. There was no operative mortality. Postoperative disturbance of ocular motility has been reduced. RMR has its scientific basis in that the medial part of the reticular formation rather than the classical lateral spinothalamic tract has more significance in the central conduction of nociceptive impulses through the midbrain level, which was verified by intraoperative neuronal recording with a tungsten microelectrode. The present report emphasizes that stereotactic mesencephalotomy, if performed meticulously and precisely, is a safe surgical procedure for pain relief. Results of MRI and sensory manifestations of a patient 11 years after RMR are also presented. PMID- 1295044 TI - Bilateral MRI-guided stereotactic cingulotomy for intractable pain. AB - As a treatment of patients with intractable cancer and noncancer pain, bilateral radiofrequency cingulotomy was performed in 10 patients. The technique involved stereotaxis using magnetic resonance guidance and local anesthesia, with the placement of a radiofrequency lesion (75 degrees, 60s). Of the 10 patients, 8 had metastatic lesions with musculoskeletal (6) or neurogenic (2) pain. Pain relief was judged excellent (4 patients), fair (1), poor (2) and excellent for 6 months poor in the last patient. The two benign lesions were neurofibromatosis with neurogenic pain and thalamic pain from an old stroke. Pain relief (with 1 year follow-up) in this group was judged excellent in one and poor in the other (thalamic pain). PMID- 1295045 TI - MRI findings of DREZ-otomy lesions. AB - Pre- and postoperative MR findings in the spinal cord of 4 patients who underwent lesioning of the cervical dorsal root entry zone (DREZ-otomy) are reported. In 3 patients with root avulsion, MR images revealed spinal cord atrophy preoperatively and, after DREZ-otomy, long-lasting spinal cord enlargement and extensive intramedullary changes. In a case without root avulsion, the preoperative MR study showed no apparent abnormality and the only postoperative MR change was a discrete lesion well confined to the dorsal horn. The findings suggested basically different post-operative pathology among patients with root avulsion and those without. MRI can be a useful supplement to autopsy study in defining postoperative spinal cord changes after DREZ-otomy. PMID- 1295046 TI - Trigeminal nucleus caudalis dorsal root entry zone: a new surgical approach. AB - New radiofrequency lesion dorsal root entry zone (DREZ) electrodes for relief of facial pain were designed based on a neuroanatomic study in man of the trigeminal nucleus caudalis at the cervicomedullary junction. The human brainstems of 3 normal postmortem specimens were sectioned with measurements and relationships of the trigeminal nucleus caudalis, segmental tracts, spinocerebellar tracts and dorsal columns. Two right-angle DREZ electrodes were made by Radionics for producing DREZ lesions in the trigeminal nucleus caudalis to treat deafferentation facial pain. PMID- 1295047 TI - Descending trigeminal tractotomy for trigeminal neuralgia after surgical failure. AB - Percutaneous rhizotomy, microvascular decompression or rhizotomy by suboccipital craniotomy often cures medically untreatable trigeminal neuralgia with an acceptable complication rate. However, pain involving the same trigeminal distribution persists in a few patients despite both rhizotomies. For 7 patients with such surgically 'failed' trigeminal neuralgia, we performed descending trigeminal tractotomy. In all patients, neuralgia ceased immediately postoperatively and has not recurred during 9 months to 15 years follow-up. Descending trigeminal tractotomy provides a satisfactory solution to this relatively rare but paroxysmal pain syndrome. PMID- 1295048 TI - Dorsal root entry zone stimulation for deafferentation pain. AB - Dorsal root entry zone (DREZ) stimulation was performed in 12 patients with chronic pain syndromes after extensive trials of medical therapy, sympathectomy or peripheral nerve stimulation had failed, with 50% of them obtaining excellent long-term benefit. Evoked potential monitoring to facilitate positioning of electrodes under either general or spinal anesthesia, and postoperatively to explore the mechanism of action, revealed findings distinct from those reported with conventional spinal cord stimulation (SCS). DREZ stimulation may function on a different neurophysiologic basis than conventional SCS, involving intersegmental processing and influencing tract of Lissauer functions or the dorsal horn directly. PMID- 1295049 TI - Percutaneous trigeminal rhizotomy and percutaneous cordotomy under general anesthesia. AB - Most percutaneous procedures for the treatment of pain are done under local anesthesia and considerable pain can be involved. If the patient is elderly or confused because of severe pain, it is difficult or impossible to perform these procedures successfully. We treated 3 elderly patients with trigeminal neuralgia and 1 patient with severe bone pain due to metastatic osteosarcoma in the lumbosacral region by percutaneous trigeminal rhizotomy and percutaneous cordotomy under general anesthesia with intratracheal intubation. We conclude that percutaneous trigeminal rhizotomy and percutaneous cordotomy can be safely done under general anesthesia. PMID- 1295050 TI - Relief from chronic pelvic pain through surgical lesions of the conus medullaris dorsal root entry zone. AB - Dorsal root entry zone (DREZ) lesions are effective in treating specific pain syndromes, most notably post-brachial plexus avulsion. There is limited experience, however, with lesions in the conus medullaris. We review the case of a patient having pelvic pain and urinary retention who failed to improve despite multiple prior interventions. Her pain was completely relieved after DREZ lesions were placed bilaterally at S2, S3, S4 and S5. The intraoperative sensory and motor evoked potential monitoring used to define the level is described in detail. PMID- 1295051 TI - Stereotactic resection and its limitations in glial neoplasms. AB - With imaging-based volumetric stereotactic techniques, it is possible to selectively and accurately remove any CT- or MRI-defined part or all of any intra axial neoplasm. However, glial neoplasms are composed of two elements: tumor tissue and isolated tumor cells which infiltrate brain parenchyma. In high-grade gliomas and pilocytic astrocytomas, the tumor tissue component is most accurately defined by the volume of contrast enhancement. Tumor tissue in low-grade nonpilocytic gliomas is indistinguishable on imaging from infiltrated parenchyma. Stereotactic biopsy is presently the only method by which CT hypodense tumor tissue can be differentiated from infiltrated parenchyma, which is also hypodense. In eloquent brain areas, stereotactic resection is appropriate for the tumor tissue component only in patients harboring glial tumors. PMID- 1295052 TI - Central pain in the absence of functional sensory thalamus. AB - Since the pioneering publication by Dejerine and Roussy, the thalamus has been commonly implicated in the pathogenesis of central pain. It is well known that cerebral lesions that spare the thalamus as well as both small and large ones within that structure produce similar pain syndromes, but could such pain develop if the thalamus were completely destroyed? CT scans of our patients suggested that it could. Moreover, exhaustive physiological explorations of the thalamus with macro- and microstimulation and microelectrode recordings in 2 more patients in whom CT scans suggested thalamic preservation despite massive suprathalamic infarcts, for the purpose of carrying out deep brain stimulation (DBS), revealed no evidence of ascending or descending diencephalic function. Their sensory examinations were similar to those of patients with congenital hemiatrophy who had undergone hemispherectomy. In 1 case, microstimulation of periaqueductal grey periventricular grey (PAG-PVG) on the unaffected side of the brain induced the spectrum of responses correctly associated with these areas and during acute stimulation nearly abolished the patient's allodynia and hyperpathia. These observations suggest that processes occurring at a subdiencephalic level (or possibly ipsilaterally) may be involved in the generation of pain. Stroke-induced central pain remains a therapeutic dilemma for the pain surgeon, and the mechanisms underlying this pain state remain a mystery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295053 TI - [Primary non-Hodgkin's malignant lymphoma of the central nervous system]. AB - The incidence of primary central nervous system lymphoma (PCNSL) is increasing, not only in immunodeficiency states, but also in apparently normal individuals. The most common presentation of PCNSL is that of an intracranial mass lesion. Ocular involvement is associated in 20% of patients. CT/MR scan typically shows one or several periventricular tumors with indistinct margins that diffusely and densely enhance following contrast infusion. The diagnosis relies on lumbar puncture, vitreous biopsy, or stereotactic biopsy of a brain lesion demonstrating lymphomatous cells. If possible, corticosteroids should be used only after definite diagnosis. Corticosteroids have a cytotoxic effect responsible for transient remission in 40% of patients. Whole brain radiation therapy induces a complete or partial response in 80% of patients but recurrence always occurs and the median survival does not exceed 14-18 months. The addition of systemic and intrathecal chemotherapy seems to substantially improve the prognosis with median survival exceeding 3 years in some studies. PCNSL associated with AIDS generally occurs at a late stage of the disease and is the fourth cause of death in AIDS patients. Radiation therapy is useful but the median survival does not exceed 5.5 months because patients most often die of opportunistic infections. PMID- 1295054 TI - [Genealogical study of oculopharyngeal dystrophy at Saguenay-Lac-St-Jean, Quebec, Canada]. AB - The genealogies of 28 proband affected with oculopharyngeal dystrophy (OPD) distributed in 28 families from Saguenay-Lac-St-Jean, a geographically isolated region of northeastern Quebec, were reconstructed. The analysis of these genealogies showed that the Montmagny and L'Islet counties are the most likely center of diffusion of OPD among the French Canadians, as suggested by Barbeau in 1966. A unique founder couple, J.E.-M.B., common to all 28 genealogies was found. The children of this couple emigrated in the 17th century from Poitou (France), a region where several families with OPD were recently ascertained. PMID- 1295055 TI - [Sublingual administration of apomorphine in the treatment of motor fluctuations in Parkinson disease]. AB - Apomorphine, a mixed dopaminergic agonist was given sublingually to 12 patients with Parkinson's disease disabled by severe on-off fluctuations. The patient's mean age was 57 years and the duration of Parkinson's disease was 12 years. All patients were also given domperidone (60 mg/day). Apomorphine was administered as soon as the off periods appeared. On periods were observed in 11 patients, with a mean apomorphine dose of 40 mg for each administration (extremes values: 20-60 mg). One patient had no motor benefit after an apomorphine dose of 120 mg. The mean duration of daily off periods was reduced by 64 per cent in 11 patients, for a mean duration of 8 months (extremes values: 2-12 months). Four patients developed stomatitis or gingival edema and stopped treatment. This pilot study shows that sublingual apomorphine, during a mean period of 8 months, significantly decreases off periods in parkinsonian patients. Others studies are necessary to confirm these results. PMID- 1295056 TI - [Autoantibodies in paraneoplastic polioencephalomyelitis: 8 cases]. AB - Antibodies directed against the central nervous system were looked for by indirect immunohistochemistry in the sera of 8 patients with paraneoplastic neurological syndrome (group 1), 21 cancer patients without neurological signs, 23 patients with miscellaneous neurological diseases and 63 normal subjects (groups 2 to 4). Four patients in group 1 had very high titres of antibodies. In 2 patients with small-cell lung carcinoma associated with sensory neuropathy the antibody recognized the cytoplasm and nucleus of all neurons. A 37 Kd protein was recognized by Western blot. A woman with cancer of the ovary and cerebellar syndrome exhibited an antibody against Purkinje's cell cytoplasm with a band of about 50-55 Kd at Western blot. In a woman with chronic uveitis and cerebellar atrophy with disappearance of Purkinje's cells the antibody (in blood and CSF) recognized certain layers of the retina as well as glial cells and cells present in the subependymal areas of the brain. Two bands of 46 and 59 Kd were revealed by Western blot. Immunoglobulins were detected in the cytoplasm of white matter cells in the cerebellum and brain stem. Among the other groups, one patient with lung cancer had a moderate titre of neuronal antinuclear antibody. The Western blot test was negative. The relevance of these antibodies for the diagnosis and treatment is discussed. PMID- 1295057 TI - [Autosomal dominant centronuclear myopathy]. AB - In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features. PMID- 1295058 TI - [Death during migraine crisis]. AB - A 42 year old man presented with a rapidly progressive syndrome, including headache, aphasia, fever, stiff neck and impaired consciousness. Following a transient improvement, the patient died after a six weeks course. The autopsy showed foci of ischaemic necrosis in the white matter of the brain. The patient's clinical history suggests the diagnosis of migraine. PMID- 1295059 TI - [Isolated memory disorders disclosing antiphospholipid antibody syndrome]. AB - Most of the neurological complications of the antiphospholipid syndrome are consequences of arterial or venous cerebral thromboses. We report the case of a 46-year-old woman presenting with the main signs of antiphospholipid syndrome: Raynaud's phenomenon, livedo, leg ulcers, repeated miscarriages, presence of a circulating anticoagulant and of antiphospholipid antibodies, who developed an isolated amnestic syndrome with a peculiar pattern; 1) almost complete sparing of the ability to learn new skills and of short-term recall; 2) deterioration, followed by disappearance of recent memories after a sufficient delay; 3) progressive alteration of increasingly old memories including knowledge memory suggested a gradual alteration of mnestic traces. The lack of neuroradiological signs of multiple infarcts suggests a direct intervention of antibodies in this patient's memorisation mechanisms. PMID- 1295060 TI - [Marchiafava-Bignami disease. Interhemispheric disconnection, favourable outcome, neurological aspect]. AB - We report two cases of Marchiafava-Bignami disease studied by CT and MR imaging. Both had hemispheric disconnection syndrome and favorable outcome. The only residual signs were agraphia with the left hand in the two cases and mild dementia in one. In one case, a control CT scan performed 3 weeks after the first one was normal whereas T2-weighted MR images showed high intensity signal in the corpus callosum. We conclude that: 1. there are benign forms of MB disease; 2. neuroimaging has diagnostic and prognostic value; 3. vitamin B deficiency may play a role in the pathogenesis of the disease. PMID- 1295061 TI - [Nociceptive threshold and Parkinson disease]. AB - It has now become possible to measure pain thresholds in man by the threshold or amplitude of the leg flexion nociceptive reflex (RIII reflex). These parameters accurately reflect the pain levels perceived by the patients. The aim of the present study was to assess pain thresholds in Parkinsonian patients, using the RIII reflex. Painful phenomena are often mentioned in Parkinson disease, but the perceived pain threshold level can be difficult to assess because of the depressive symptoms which are often associated with Parkinson disease. In 8 cases out of 10, the pain threshold was found to be higher in patients with Parkinson disease than in a control population of the same age: in 2 cases, naloxone injection led to recovery of the normal pain threshold level. PMID- 1295062 TI - [Pick disease]. PMID- 1295063 TI - Immunohistochemical evidence of high concentrations of metallothionein in pancreatic hepatocytes induced by cadmium in rats. AB - A recent study from our laboratory has shown that cadmium, a toxic heavy metal, is one of the most effective agents known for inducing hepatocytic transdifferentiation of the rat pancreas. With repeated injections of cadmium, the incidence of rats with pancreatic hepatocytic foci can be as high as 93%. Cadmium is also well known as a very potent inducer of metallothionein, a metal binding protein that appears to be important in the biologic response to several toxic heavy metals in most tissues, including the pancreas. Therefore, the present study sought to determine if metallothionein was associated with cadmium induced transdifferentiation of pancreatic cells. Expression of metallothionein was studied immunohistochemically by the peroxidase-antiperoxidase method in tissue sections of the pancreas of rats with pancreatic hepatocytes. High levels of metallothionein were localized primarily within the pancreatic hepatocytes. Surrounding normal pancreatic islet and acinar cells were not immunoreactive. Thus, metallothionein is expressed actively in cells transdifferentiated to hepatocytes by cadmium within the pancreas. PMID- 1295064 TI - Spontaneous skin neoplasms in aged Sprague-Dawley rats. AB - A total of 93 tumors of the epidermis, its appendages, and dermis were observed in 1,433 (717 males, 716 females) rats employed in oncogenicity studies over a 2 yr period. Mammary gland neoplasms will be reported separately. Fifty-seven (61.3%) were epithelial with 49 in males and 8 in females. Keratoacanthoma was the most frequent epithelial neoplasm in males (22) followed by squamous cell carcinoma (11) and papilloma (5). Sebaceous gland neoplasms seen in males (5) included both adenomas (3) and carcinomas (2). In males, there were also 3 trichoepitheliomas, 1 pilomatricoma, 1 basal cell tumor, and 1 malignant melanoma. Of the 8 epithelial neoplasms in females, there were 3 squamous cell carcinomas, 2 keratoacanthomas, and 1 each basal cell tumor, malignant melanoma, and trichoepithelioma. There were 21 mesenchymal neoplasms in males and 15 in females. The most frequent neoplasm was fibroma (7 males, 8 females) followed by lipoma (7 males, 4 females) and fibrosarcoma (4 males, 3 females). One male had a liposarcoma and 2 males each had hemangioma. The total neoplasm incidence of 70/717 (9.8%) in males and 23/716 (3.2%) in females showed that skin neoplasms were 3 time more common in males than in females. Epithelial neoplasms of the skin were 6 times more common in males than in females. Males were more than twice as likely to have epithelial rather than mesenchymal skin neoplasms whereas the reverse was seen in females. PMID- 1295065 TI - Experimental renal papillary necrosis in the Mongolian gerbil (Meriones unguiculatus). AB - Sequential light microscopic and ultrastructural examination of kidneys from male and light microscopic examination of female Mongolian gerbils given 250 mg 2 bromoethylamine hydrobromide (BEA)/kg body weight ip were performed. In addition, male Mongolian gerbils were treated with both BEA and ip injections of either water, dimethyl sulfoxide, piperonyl butoxide, or reserpine. Light microscopic renal lesions in male Mongolian gerbils progressed from congestion of the vasa recta of the proximal inner medulla at 6 hr post-treatment to total renal papillary necrosis (RPN) at 24 hr post-treatment. There was no sex difference in sensitivity to BEA. Ultrastructural alterations in male gerbils were restricted to the vasa recta. Vascular lesions of endothelial swelling and pericapillary edema in the vasa recta of the proximal inner medulla was observed 2 hr post treatment and progressed to occlusion by platelets adherent to exposed basement membranes at 6 hr post-treatment. Diuresis induced by injections of saline and injections of dimethyl sulfoxide or piperonyl butoxide did not affect the development of BEA-induced RPN. Reserpine slowed the development of BEA-induced RPN by its vasodilatory effect on the renal vasculature, not by blocking the endothelial toxicity of BEA. RPN induced by BEA in the Mongolian gerbil is apparently an ischemic necrosis of the inner medulla that develops secondary to endothelial damage of the vasa recta. PMID- 1295066 TI - Spontaneous corneal dystrophy and generalized basement membrane changes in Fischer-344 rats. AB - Groups of young, sexually mature Fischer-344 rats (n = 25/sex) obtained from commercial breeders were examined ophthalmologically and histopathologically to determine the prevalence and severity of corneal basement membrane lesions (corneal dystrophy) and basement membrane changes in select nonocular tissues. Results disclosed a high incidence of corneal basement membrane dystrophy in rats of both sexes from all breeders; however, severity levels were significantly increased in rats obtained from one breeder when compared to others. Furthermore, rats that displayed the most advanced corneal lesions also exhibited more severe basement membrane changes in other organs, especially renal tubules and vascular internal laminae. These findings suggest that both ocular and nonocular dystrophic changes may have been linked through common physiologic (or genetic) mechanisms. Animals that displayed basement membrane lesions were not considered to represent compromised biologic test systems. PMID- 1295067 TI - Nasal lesion development and reversibility in rats exposed to aerosols of dibasic esters. AB - This study was conducted to investigate the initial tissue damage, morphogenesis, and reversibility of nasal lesions induced by the inhalation of dibasic esters (DBE). Young male rats were exposed, nose-only, to an aerosol/vapor mixture of DBE at a concentration of 5,900 mg/m3 for 4 hr and subsequently killed at 1, 4, 7, 14, 21, and 42 days after exposure. Nasal lesions were distributed along major inspiratory airflow routes. Widespread epithelial denudation occurred in the anterior nasal cavity, but the lesions were confined to the dorsal meatus, adjacent the nasal septum, and the lateral middle meatus in the mid-anterior nasal cavity. The lesions were markedly less severe in the posterior nasal cavity and sharply confined to the tips of dorsal ethmoturbinates and adjacent nasal septum. The damaged cuboidal/nonciliated and respiratory epithelium in the anterior nasal cavity regained a normal structure by 4 and 7 days postexposure, respectively. The regeneration of damaged olfactory epithelium was related to the severity of initial tissue damage. Slightly damaged epithelium regained a normal appearance within 1-2 weeks, but the extensively denuded epithelium of the dorsal meatus in the anterior nasal cavity failed to regain a normal structure by 6 weeks. The sustentacular cells of the olfactory epithelium appeared to be the initial site of DBE nasal injury. In the early stages of regeneration, the epithelium was repaired by proliferating stem cells derived from basal cells. Numerous mitotic figures and bromodeoxyuridine labeling were found in the regenerating basal cells, stem cells, and sustentacular cells at 4 and 7 days. As repair processes advanced, the numbers of olfactory neurons and vesicles were increased with a proportional decrease in stem cells. PMID- 1295068 TI - Studies of skin toxicity in vitro: dose-response studies on JB6 cells. AB - There are many reasons for developing in vitro tests of toxicity including cost, speed, studies of mechanisms, and studies utilizing human cells and tissues. The present study focuses on the development of in vitro tests to predict in vivo toxicity by comparing them to data from the literature. A broad spectrum of model toxic compounds was evaluated for toxicity on mouse skin JB6 cells in culture. These included mercuric chloride, sodium lauryl sulfate, formaldehyde, dimethyl sulfoxide, benzoyl peroxide, and ionomycin, all of which have been proven to be positive in the Draize test or in cutaneous toxicity studies. Cell viability was evaluated every 15 min for up to 1 hr, and then after 24 hr of treatment using the Trypan Blue exclusion method; morphological changes were evaluated using phase-contrast and transmission electron microscopy. Dose- and time-dependent cell death and morphological changes were observed at concentrations ranging from 10(-14) to 10(-2) M. Arbitrary rankings were assigned based on 1) IC50 value estimated from the present data, and 2) in vivo toxicity reported in the Registry of Toxic Effects of Chemical Substances. Good correlation between in vitro and in vivo toxicity based on arbitrary rankings was observed. Thus, these findings suggest that the JB6 cell culture model can be used for predicting in vivo toxicity. In the future, it may be possible to utilize this system for the study of intracellular ionized calcium ([Ca2+]i), and the expression of oncogenes as early indicators of toxicity. PMID- 1295069 TI - Parenteral aluminum compounds produce a local toxic myopathy in rats: importance of the anion. AB - Aluminum lactate, injected in rats, produced skeletal muscle necrosis of diaphragm and abdominal wall subjacent to peritoneal surfaces. Deeper muscle cells (distal from inoculum) were less severely affected. Ultrastructural studies of diaphragm revealed inoculum coating collagen fibrils, aggregating next to muscle basal lamina and localized within phagocytes. Aluminum lactate penetrated lymphatic vessels and caused reactive changes on the pleural as well as peritoneal surfaces of diaphragm. In contrast, injection of aluminum citrate did not produce myopathy. Also, mixtures of aluminum lactate with aluminum citrate, sodium citrate, or another chelating agent failed to produce myopathy. Therefore, the regional myopathy produced by the lactate salt provides a model for in vivo cytotoxicity of aluminum in which anionic binding is a critical determinant. PMID- 1295070 TI - Morphology of nasal lesions induced in Osborne-Mendel rats and B6C3F1 mice by chronic inhalation of allyl glycidyl ether. AB - Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epithelium and degeneration and regeneration with subsequent squamous and/or respiratory metaplasia of the olfactory epithelium were observed in many AGE exposed animals. Three primary nasal neoplasms (1 papillary adenoma, 1 squamous cell carcinoma, and 1 olfactory epithelial carcinoma) were observed in rats exposed to 10 ppm AGE, and 1 nasal papillary adenoma was observed in a rat exposed to 5 ppm. Four papillary adenomas and 2 hemangiomas were observed in the noses of mice exposed to 10 ppm AGE. Although the incidence of primary nasal tumors in AGE-exposed rats or mice was not statistically significant compared to the incidence in concurrent controls, the relative rarity of primary nasal tumors in historical controls and the concurrent presence of metaplastic and hyperplastic nasal lesions similar to those reported to be associated with induced tumors of nasal epithelia by other chemicals suggest that the nasal tumors observed may be related to AGE exposure. It was concluded that, in addition to lesions indicating a toxic effect on the nasal mucosa, inhalation exposure to AGE for 24 months resulted in some evidence of carcinogenicity of AGE for male mice, equivocal evidence of carcinogenicity for female mice and male rats, and no evidence of carcinogenicity for female rats. PMID- 1295072 TI - Quinolone arthropathy--acute toxicity to immature articular cartilage. AB - A class effect of quinolone antibacterial agents observed during animal toxicity testing is a specific arthropathy (QAP). Despite the growing list of laboratory animals susceptible to QAP and reports of arthralgia in patients treated with quinolones, the potential for QAP development in humans remains unknown. This review discusses current concepts in the biology of articular cartilage and how these concepts elucidate QAP pathogenesis. Biomechanical forces within synovial joints and toxicokinetic properties of quinolones contribute to QAP induction. Since a limited number of mechanistic pathways exist for acute articular damage, QAP may serve as a research tool to probe the pathobiology of injury to articular cartilage. PMID- 1295071 TI - Feeding studies in rats with mineral hydrocarbon food grade white oils. AB - This investigation compared the effects of feeding rats diets containing food grade white oil processed by either conventional oleum treatment or the more modern method of catalytic hydrogenation. In two separate experiments, male or female Fischer-344 rats were given free access for 90 days to diets containing 0, 10, 100, 500, 5,000, 10,000, or 20,000 ppm of either oleum-treated white oil (OTWO) or hydrotreated white oil (HTWO). There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by hematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several hematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method. PMID- 1295073 TI - Response of the esophageal epithelium to concomitant cis dichlorodiammineplatinum(II) and radiation treatment. An electron microscopic study in rabbits. AB - The rabbit esophageal mucosa was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose 2, 6, 10. 16 or 20 Gy). Fifteen to forty five minutes before the start of each irradiation 0.3 mg Cis dichlorodiammineplatinum (cis-DDP, cisplatinum) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of damage with cell loss and structural disarrangement of the microridges and whorls on the surface. However, with further treatment the esophageal mucosa exposed to cis-DDP and radiation normalized faster and more complete compared to the esophageal part exposed to cis-DDP alone. The difference may depend on an accelerated proliferation in the part of the trachea that is exposed to a combined treatment. PMID- 1295074 TI - Ultrastructural effects of therapeutic irradiation on human epithelial tumors. AB - Irradiation induces several cellular changes leading to death of cancer cells and normal cells which is followed by repairing processes of normal cells. We have studied the effects of therapeutic irradiation on head and neck cancers. Tissue samples taken before and during the radical irradiation (50-80 Gy) of the squamous cell carcinomas of the head and neck region were examined by light and electron microscopy. Nuclear atypia was most pronounced cellular change during irradiation. The tumor invasion pattern remained unchanged but the number of mitoses decreased. Lymphocytic infiltration increased at the beginning of the therapy (from 10 to 30 Gy) but decreased at the end of radiotherapy. The amount of neutrophils and the keratinization pattern remained almost unchanged at the light microscopical level. However, by electron microscopy, intracellular filaments and desmosomes tended increase slightly especially in tumors responding more favorable to the treatment. The changes in nuclear morphology pointing in a more undifferentiated direction are considered to be due to cell damage rather than to a more aggressive behavior of the tumor cells. This is in agreement with the simultaneous decrease in mitoses, which might partly be due to radiation induced arrest of tumor cells to the G2 phase. These observed changes correspond to animal studies in the literature and might be responsible for the disappearance of tumors during irradiation. PMID- 1295075 TI - Information and misinformation regarding ischemia of heart muscle tissue. The cause of cell death during blood reperfusion and reactivation of heart muscle tissue after prolonged ischemia. AB - An electron microscopic study of heart muscle tissue exposed to six hours ischemia and prepared according to the low denaturation embedding technique revealed a structural modification confined to the mitochondrial cristae. The modification consisted of a removal of Krebs cycle enzymes from the cristae. Reperfusion of the ischemic tissue after four hours ischemia led to extensive breakdown of the mitochondrial structure and contractility could not be restored. However, when after six hours ischemia the ischemic tissue was reperfused with blood, the composition of which had been modified to stimulate mitochondrial function, no additional structural changes were observed and contractility was restored. The structural damage caused by reperfusion with non modified blood is explained by a loss of control of plasma membrane permeability caused by impaired ATP production which makes the ionic composition of the cytosol approach that of blood plasma, stopping oxidative phosphorylation. A treatment to restore heart muscle function after long periods of ischemia and after heart transplantation is proposed. The structural damage revealed that the Krebs cycle and the respiratory chain enzymes are associated according to a regular periodic pattern and that the enzyme molecules are closely aggregated three-dimensionally. Earlier electron microscopic studies revealing massive structural deterioration of heart muscle cells already after 45 to 60 minutes ischemia leading to the conclusion that the cells are irreversibly damaged, is based on fixation artifacts caused by osmium fixation. This study has been carried out in collaboration with the research team of Gerald D. Buckberg at the Thoracic Surgery Division at University of California at Los Angeles. PMID- 1295076 TI - The effect on the ultrastructure of dental enamel of excimer-dye, argon-ion and CO2 lasers. AB - This study aimed to investigate the ultrastructural changes that occur in dental enamel irradiated with pulsed excimer-dye, continuous-wave (CW) argon-ion and CW CO2 lasers. The pulsed excimer-dye laser produced deep craters, rough damaged surfaces with underlying porosity and amorphous vitrified material. The vitrification of the enamel indicated that the temperature in these areas must have been at least in the range 1280 to 1600 degrees C. The CW argon-ion laser irradiation produced a changed non-cratered surface with inter-crystalline porosity and a mixture of small and some large irregularly packed recrystallized enamel crystals. The CW CO2 laser produced shallow craters, surface crazing and lifting off the removal of the surface layer to expose the underlying roughened enamel. The ultrastructure revealed inter- and intra-crystalline porosity, a mixture of small but variable size irregularly packed recrystallized enamel crystals and also well packed large crystals which indicated further grain growth. The porosity in lased enamel was overall very similar to that seen in enamel heated in an electric furnace to a temperature of 600 degrees C. The presence of recrystallized enamel crystals indicated a temperature rise of approximately 1000 degrees C and the grain growth indicated that a temperature > or = 1000 degrees C existed for some time after the laser irradiation. In general the excimer-dye laser produced most surface destruction because of its higher power density and shorter interaction time and the argon-ion laser produced least damage. These results indicated that the lasers used in this study require much more refinement before they can find therapeutic application to dental enamel, and this may well be the case for other lasers being investigated for clinical dental practise. PMID- 1295077 TI - Dentinogenesis and the calciotraumatic response to the injection of lead or fluoride ions. AB - A number of ions can disturb the formation of dentine resulting in a calciotraumatic response. The calciotraumatic response following the injection of sodium fluoride was investigated using backscattered electron imaging in the scanning electron microscope and compared with the response to lead acetate. With fluoride, there was formation of a hypermineralized band succeeded by a relatively hypomineralized band, but with lead acetate, only a hypomineralized band was produced. However, there were some differences in the response between the labial and lingual dentine with both ions. In the labial dentine following injection of sodium fluoride, the onset of hypermineralization was less abrupt than in the lingual dentine. Furthermore, the transition from hypermineralization to relative hypomineralization was more abrupt in the labial dentine. Sometimes there was an increased thickness of labial dentine between the hypermineralized layers towards the apex of the tooth and this dentine was less homogeneously mineralized. Normal incremental lines were occasionally seen both labially and lingually. Lead acetate produced a more severe disruption of dentine formation labially than lingually. These differences in response may be related to the pattern of mineralization labially and lingually and to the systemic effects following the injection of sodium fluoride. PMID- 1295078 TI - Microwear studies of early African hominid teeth. AB - Studies of microwear on fossil hominid teeth have become an important approach in paleoanthropology. Since there are very few samples of early hominids from East Africa with suitable teeth, this paper presents a review of the occurrence of some dental wear characteristics to provide a data base for reconstructing the diet of the early hominids. Distinctive microwear features such as furrows, crenulations, stress lines and deep grooves, are interpretive tools that can be used in a biomechanical approach. Occurrence of the same dental microwear patterns in extant species with known dietary differences is indicative of foods that have probably been exploited in fossils. PMID- 1295079 TI - Scanning electron microscopy of intracellular organelles in the young odontoblasts of rats. AB - Intracellular structures of the odontoblasts were studied by scanning electron microscopy (SEM) using a modified AODO (aldehyde prefixed-osmium-DMSO-osmium) method. Well-developed flattened and layered rER (rough endoplasmic reticulum), paved with its associated ribosomes on its outer surface, were clearly observed in the odontoblast. Branched tubular mitochondria with nodules and swollen endings, interposing between and passing through the fenestrated layered rER, were demonstrated in the functional cells. Oblique and cross-sections of both the rER system and tubular mitochondria showed orthodox configurations similar to those usually described in transmission electron microscopy (TEM) studies. Many finger-like projections constructing the cristae directing towards the inner mitochondrial chamber were observed, and external chamber extending into the tubular cristae was also demonstrated. PMID- 1295080 TI - Microvasculature of normal and hydropic labyrinth. AB - The microvasculature of the inner ear in guinea pigs and humans was observed with a scanning electron microscope using corrosion casting method. Alterations in the inner ear vasculature which occurred in association with experimental endolymphatic hydrops were also investigated. The results thus obtained are summarized as follows: 1. In the cochlea and vestibule, the arteries, coiled arterioles, and the veins are endowed with their respective characteristic morphologic features and play a role in the regulatory mechanisms of circulation. 2. The point in humans which is most different from guinea pigs was that coiled arterioles in the cochlea and the coil-like traveling of the anterior vestibular artery is not outstanding. 3. Arteriovenous anastomoses were demonstrated to exist in lateral wall of cochlea and utricular macula, a finding suggesting the existence of a regulatory mechanism for local blood flow. 4. Endolymphatic hydrops was noted to be preferentially associated with vascular abnormalities in the lateral wall of the cochlear duct and in the saccular macula, among other vestibular structures. PMID- 1295081 TI - Scanning electron microscopy of nerve fibers in the dog cochlea. AB - The nerve fiber arrangement inside the organ of Corti in the dog was studied. Thick sections were cut serially from celloidin-embedded cochleas and observed with a scanning electron microscope (SEM). The nerve fibers in the organ of Corti were clearly exposed in sections cut in the horizontal plane. The arrangement of nerve fibers in the dog showed considerable difference from that of other species. The tunnel basilar fibers in the dog curved basalward, and took a long longitudinal course to form a broad bundle in the center of the tunnel floor. This bundle has not been found in adult animals of other species. Two distinct types of tunnel radial fibers, upper tunnel radial fibers and underpassing radial fibers, were recognized. The latter type of radial fibers ran beneath the bundle of basilar fibers, and seemed to be characteristic of the dog cochlea. From the morphological characteristics, these underpassing radial fibers were thought to be efferent in nature. PMID- 1295082 TI - Cochlear and vestibular epithelia from a patient with Meniere's disease: a case study. AB - Scanning electron microscopy observations were carried out on the cochlear and vestibular epithelia of the left temporal bone of a Meniere's patient. There was almost complete absence of hair cells in the basal turn of the cochlea. The outer hair cells of the second turn presented an abnormal shortening of the shorter stereocilia within a tuft, reminiscent of the specific atrophy of the short and middle stereocilia in the ciliary tufts of outer hair cells in the guinea pig with experimental hydrops. The cilia of the inner hair cells showed fusion and giant cilia formation. Hair cells were observed in the apical turn which showed no pathological features in particular. In the saccular epithelium there were a number of striking features including, loss of the kinocilium, loss of ciliary tufts, swelling of the sensory cells, holes in the epithelium, and sensory cells pushed out and lying on the surface. The utricular epithelium was less perturbed and showed only relatively small protrusions from the epithelial surface. Similar observations have earlier been made on the vestibular epithelium in experimental hydrops. After taking into consideration the relatively long delay to fixation (12 hours) it appeared that the sacculus was more fragile and prone to autolysis than the other organs suggesting that the in-vivo pathology was manifested in particular in that organ as would be predicted from Meniere's symptoms. PMID- 1295083 TI - Comparison of cryopreparation techniques for electron probe microanalysis of cells as exemplified by human erythrocytes. AB - Erythrocytes in human blood were used to evaluate the reliability of cryopreparation techniques for electron probe X-ray microanalysis of biological cells and tissues. The elemental content determined by X-ray microanalysis of ultrathin freeze-dried cryosections was found to be consistent with data known from the literature. Considerable redistribution of the intracellular elemental composition was found after freeze-substitution as well as after freeze-drying followed by resin embedding. Two conclusions are drawn from this study: 1. Erythrocytes in human blood are a suitable reference specimen for evaluation of specimen preparation techniques for microanalysis. 2. At present, freeze-dried cryosections are the most reliable specimen type for quantitative electron probe microanalysis of cells. PMID- 1295084 TI - Effect of chronic treatment with diuretics on mouse liver: a morphological and microanalytical investigation. AB - In an attempt to produce an animal model for the disease cystic fibrosis (CF), mice were treated chronically with the diuretics amiloride and furosemide, in order to cause chronic inhibition of transepithelial ion transport. Experiments were carried out on adult mice (2 months treatment); in addition, pregnant mice were treated with diuretics, and tissue from offspring 2 and 7 days post partum was investigated. Since biliary cirrhosis is a common occurrence in CF, hepatocytes in the treated mice were investigated by X-ray microanalysis and by light and electron microscopy. Treatment with amiloride caused a significant decrease in cellular Na concentration in adult animals and in in utero treated mice 2 days after birth. The decrease in Na was paralleled by a decrease in Cl, but K levels were not affected. Furosemide caused a slight increase of cellular Na concentrations, especially in animals aged 7 days. In the adult animals, both amiloride and furosemide caused a significant decrease of the cellular Na and Cl levels. No signs of cirrhosis could be observed. Inconsistent changes in the accumulation of lipid droplets in hepatocytes of adult animals treated with amiloride were observed by electron microscopy. It can be concluded that chronic treatment with diuretics, even though it causes some, possibly pathological, changes of the liver, is only of very limited value for generating an animal model to study liver disease in CF. PMID- 1295085 TI - Atomic force microscopy of DNA on mica and chemically modified mica. AB - Atomic force microscopy (AFM) was used to image circular DNA adsorbed on freshly cleaved mica and mica chemically modified with Mg(II), Co(II), La(III), and Zr(IV). Images obtained on unmodified mica show coiling of DNA due to forces involved during the drying process. The coiling or super twisting appeared to be right handed and the extent of super twisting could be controlled by the drying conditions. Images of DNA observed on chemically modified surfaces show isolated open circular DNA that is free from super twisting, presumably due to strong binding of DNA on chemically modified surfaces. PMID- 1295086 TI - Investigation of living cells in the nanometer regime with the scanning force microscope. AB - Membrane structures of different types of cells are imaged in the nanometer regime by scanning force microscopy (SFM). The images are compared to those obtained with a scanning electron microscope (SEM). The SFM imaging can be done on the outer cell membrane under conditions that keep the cells alive in aqueous solutions. This opens up the possibility of observing the kinematics of the structures that determine the interaction of a cell with its environment. Therefore, STM observations, together with information obtained with the electron microscope, open up new ways of studying the development of biological structures. With the currently possible resolution, the SFM gives access to processes such as antibody binding or endo- and exocytosis, including processes correlated to the infection of cells by viruses. PMID- 1295087 TI - The arthritis of familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) is a disease of unknown etiology and pathogenesis. In addition to fever, arthritis is among its most frequent manifestations. The arthritis of FMF is typically an acute, episodic, self limited process with no sequelae. The radiographic features of FMF arthritis are usually limited to transient, often severe osteoporosis. Synovial fluid analysis many mimic septic arthritis with very high white blood cell counts; cultures are uniformly negative. The course of FMF is almost always benign, with no residual articular incapacity. Some patients, limited to certain ethnic groups, develop renal amyloidosis. Colchicine therapy modifies the natural history of the disease by decreasing the attack frequency and preventing amyloid deposition. At present, a lipocortin deficiency appears to be the likely candidate for a pathogenic mechanism. An unusual case with dramatic periarticular features (periostitis) and a protracted course with an excellent response to synovectomies is reported here. There is no explanation for the exuberant periarticular bone formation noted in this case, but a variety of recently discovered growth factors may be implicated. PMID- 1295088 TI - POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature. AB - A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement. PMID- 1295089 TI - Rheumatic complications of alcohol abuse. AB - The purpose of this report is to review rheumatic complications associated with alcoholism. Data were collected by an English-language literature search using MEDLINE (1966 to December 1991) and references from identified articles. Studies in humans, including case reports of joint disease and allied disorders associated with alcoholism, were reviewed. According to the data identified, alcoholism is associated with many rheumatic problems, including neuropathic arthropathy, hyperuricemia with gouty arthritis, septic arthritis, and joint hypermobility. Osteoporosis, osteonecrosis, and myopathy also are common. Several other rare musculoskeletal complication have been described. Early recognition of these problems is important for management. Further studies are needed to examine the effect of alcohol on connective tissue components in joints. PMID- 1295090 TI - Dyslipoproteinemia in the course of active rheumatoid arthritis. AB - Concentrations of serum lipids and serum very low-density lipoproteins and low density lipoproteins (VLDL+LDL, originally called beta lipoproteins) were measured and agarose gel electrophoresis of serum lipoproteins was performed in 69 patients with active rheumatoid arthritis (RA), 40 patients with psoriatic arthritis (PA), 21 patients with osteoarthritis (OA), and 65 healthy blood donors. These lipid parameters were also compared in 21 RA and 40 PA patients during periods of severe disease activity (SA) versus minimal disease activity (MA). RA patients had significantly decreased concentrations of total serum lipids, total serum cholesterol, cholesterol in LDL, and cholesterol in high density lipoproteins (HDL) compared with healthy blood donors. RA patients with SA had significantly decreased cholesterol in LDL and HDL compared with patients with MA. As the disease activity decreased, RA patients had normalization of almost all serum lipid concentrations. Electrophoresis of serum lipoproteins showed heterogeneous patterns in RA patients. Patients with PA also had some evidence of dyslipoproteinemia. Serum lipids changed with disease activity in PA patients in a manner similar to that in RA patients. These data show that patients with RA and PA have a dyslipoproteinemia that is related to disease activity. PMID- 1295091 TI - Geographic distribution of rheumatoid arthritis in ancient North America: implications for pathogenesis. AB - The fifth centennial of Columbus stimulates renewed interest in New World origins of disease. The earliest documentation of rheumatoid arthritis was in the New World. Subsequent study of its distribution in the New World in antiquity defines localization to a very specific geographic region. The absence of rheumatoid arthritis in 63 archaeological sites surrounding the original "catchment area" and in five Old World sites, with documented spread over time, suggests that it is a vector (microorganism or allergen)-transmitted disease. PMID- 1295092 TI - Diseases associated with calcium pyrophosphate deposition disease. AB - Although many metabolic and endocrine diseases have been reported to predispose to calcium pyrophosphate dihydrate crystal deposition, the validity of many of these associations remains unclear. A critical review of the literature relating to these associations, with illustrative cases and data derived from the authors' own experience, is presented. It is concluded that there is good evidence to associate hypophosphatasia, hypomagnesemia, and hyperparathyroidism with chondrocalcinosis and acute attacks of "pseudogout." Meta-analysis also suggests a small but significant association between hypothyroidism and chondrocalcinosis. Hemochromatosis stands alone in clearly associating not only with chondrocalcinosis but also with structural change and chronic arthropathy. The biochemical mechanisms that may produce these various associations are discussed. Recommendations are made concerning appropriate screening for metabolic and endocrine disease in patients with chondrocalcinosis. PMID- 1295093 TI - Laryngeal involvement in systemic lupus erythematosus. AB - Laryngeal involvement in systemic lupus erythematosus (SLE) can range from mild ulcerations, vocal cord paralysis, and edema to necrotizing vasculitis with airway obstruction. In this report, four cases showing the range of severity of this disease manifestation are presented, accompanied by a comprehensive review of the literature. The clinical course of 97 patients with laryngeal involvement with SLE are reviewed, of whom 28% had laryngeal edema and 11% had vocal cord paralysis. In the majority of cases, symptoms such as hoarseness, dyspnea, and vocal cord paralysis resolved with corticosteroid therapy. Other, less common causes of this entity included subglottic stenosis, rheumatoid nodules, inflammatory mass lesions, necrotizing vasculitis, and epiglottitis. The clinical presentation of laryngeal involvement in patients with SLE follows a highly variable course, ranging from an asymptomatic state to severe, life-threatening upper airway compromise. With its unpredictable course and multiple causations, this complication remains a diagnostic and therapeutic challenge to physicians involved in the care of patients with SLE. PMID- 1295094 TI - Penetrating trauma audit--TRISS analysis. AB - Quality assurance in trauma care is of major importance in assessing the efficacy of a trauma service and in identifying areas for improvement. Trauma scores and the TRISS methodology are at present the most accurate tools for quality assurance purposes. In this prospective study, the TRISS methodology was used to analyse the results in a group of 629 patients with penetrating trauma. PMID- 1295095 TI - [Partial ileal bypass for familial hypercholesterolemia]. AB - The extent of reduction in cholesterol levels, the maintenance of low levels in the long-term, the morbidity and mortality as well as the acceptance of side effects of the partial ileal bypass (PIB) is reviewed. The mean reduction in cholesterol levels following PIB was 35.2% in males and 35.8% in female patients. The reduction is significant and it is maintained over a 10-year period. The morbidity and mortality is low and side-effects are well tolerated. Our results indicate that the PIB may play an important role in the cholesterol-lowering armamentarium. PMID- 1295096 TI - A review of carcinoma of the colon and rectum over a 3-year period at Hillbrow Hospital, Johannesburg. AB - Fifty-one patients with adenocarcinoma of the large bowel seen at Hillbrow Hospital over a 36-month period are reviewed. The mean age at diagnosis was 53 years. Advanced disease was present in at least 60%. Carcinoma of the rectum constituted 48% and colonic carcinoma 52%. Cancer and polyps of the large bowel in urban blacks are no longer a rarity in urban hospitals. PMID- 1295097 TI - An unusual rectal carcinoma. A case report. AB - The case history of a patient whose barium enema radiographs confirmed the clinical diagnosis of a stenosing rectal carcinoma is presented. Two years previously, the patient had undergone sub-total gastrectomy for carcinoma of the gastric antrum. An abdominoperineal excision of the rectum was performed, and histological examination of the tumour showed it to be not primary large bowel in origin, but a metastatic manifestation of the original gastric cancer. PMID- 1295098 TI - The wandering ampulla--duodenal-jejunal intussusception of a carcinoid tumour with displacement of the bile duct to the left iliac fossa. A case report. PMID- 1295099 TI - Total gastrectomy for gastric cancer associated with situs inversus totalis. A report of 2 cases. AB - A 69-year-old man and a 54-year-old woman with situs inversus totalis were admitted to our hospital for surgery for gastric malignant disease. The diagnosis was made radiologically and successful total gastrectomies were performed. PMID- 1295100 TI - The management of clinically occult breast lesions. A Johannesburg learning experience. AB - There is an increase in demand for pre-operative radiologically guided percutaneous localisation of occult breast lesions. Specific problems in the progression from mammographic identification to histological diagnosis are cited. Accurate pre-operative localisation should always be followed by specimen radiography. PMID- 1295101 TI - Postoperative intensive care and the South African Society of Anaesthetists' patient category. AB - A group of 412 postoperative patients admitted to an intensive care unit of an academic hospital were evaluated in terms of their need for intensive care. The Acute Physiology and Chronic Health Evaluation score, the Therapeutic Intervention Scoring System (TISS) and the South African Society of Anaesthetists' (SASA) patient category were utilised to determine the level of care required by each patient. A further objective of the study was to determine if the SASA patient category, on its own, adequately described the need for intensive care in postoperative patients. Evaluation of the data indicated that, in terms of TISS, 66% of the patients required intensive care. These patients were distributed throughout all three SASA categories. Of the 137 patients who, according to TISS, did not require intensive care, 122 were SASA category 3 patients. However, of the total number of category 3 patients, just less than half required intensive care. In order to identify better those patients within a specific SASA category who require intensive care we suggest further subdivision of each category into groups A, B and C, according to the number of TISS points scored at 24 hours postoperation. In this way a retrospective audit using SASA categories would clearly identify those postoperative patients who required intensive care. PMID- 1295102 TI - Extending patient-controlled analgesia to patient-controlled neuroleptanalgesia. AB - A trial was conducted (among 22 patients) to assess a new use of patient controlled devices. Using a patient-controlled analgesia (PCA) pump under the anaesthetist's guidance, the patients self-administered a neurolept mixture consisting of droperidol and alfentanil. The patients were then able to undergo minor surgery (dilatation and curettage). The majority remained detached, sedated and pain-free, while able to control the PCA pump during the procedure. Patient controlled neuroleptanalgesia or PCNA, as we propose to call this technique, appeared practical, effective and safe. The method was generally well accepted and highly rated by the patients. PMID- 1295103 TI - Long-term results of Charnley low-friction arthroplasty of the hip. AB - The long-term results of 488 Charnley low-friction arthroplasties, performed by one surgeon, were analysed. Radiological changes were assessed using the CART nomenclature. If sepsis (1.4%) is excluded, the mechanical failure rate of one or both components requiring revision surgery was 6.5%. The incidence of radiological loosening of components was 4.7%. Kaplan-Meier survival analysis predicts an 88% mechanical survival of components at 10-12 years. PMID- 1295104 TI - Traumatic dislocation of the hip in children. A report of 4 cases. AB - During a 1-year period 4 children, aged 4-14 years, suffering from traumatic dislocation of the hip were treated at H. F. Verwoerd Hospital. This is a rare injury and constitutes 0.335% of injuries seen in this unit. Two cases of anterior dislocations, which are even more rare, are included in this study. This article emphasises the importance of this injury in all cases of children subjected to severe trauma. However, as illustrated by 1 case, mild trauma may be sufficient to cause a dislocated hip in the young child. PMID- 1295105 TI - [Does a correlation exist between positive wound cultures at the end of an operation and later wound and prosthetic sepsis?]. AB - A prospective study was carried out on 51 patients in whom a reconstructive vascular procedure was performed in order to determine whether any correlation between positive wound cultures at the end of the operation and later wound and/or prosthetic sepsis exists. Swabs were taken from all surgical wounds and cultured for aerobic and anaerobic organisms. The patients were monitored for 72 89 months and all instances of wound or prosthetic sepsis thoroughly investigated. The incidence of positive wound cultures was 13%, with a variety of organisms present. No increased incidence of wound or prosthetic sepsis was observed in patients with positive wound cultures. The incidence of wound sepsis was 3.7% and of prosthetic sepsis 2%. No correlation was found between organisms cultured during operation and organisms isolated from septic wounds. The 1 case of prosthetic sepsis (at 19 months postoperatively) was probably due to secondary haematogenous infection. PMID- 1295106 TI - Hypocalcaemia during surgery for ruptured De Bakey type III thoracoabdominal aneurysm. A case report. AB - A case of a leaking De Bakey type III thoraco-abdominal aneurysm is reported. The ischaemic liver resulting from prolonged aortic cross-clamping, extensive blood loss, citrated homologous blood replacement and low calcium levels is discussed. It is suggested that during aortic clamping the ischaemic liver cannot metabolise the excess citrate in homologous blood and recommend that homologous blood is avoided during this period--crystalloids and heparinised blood being used instead of citrated blood. PMID- 1295107 TI - Free plantaris (or tendo Achillis) osseotendinous transfer to restore finger flexion. AB - A new method to restore flexion of fingers is described whereby the plantaris tendon (or part of the tendo Achillis), with its bony insertion, is transferred to the finger. Strong bony anchorage is achieved in the distal phalanx, while a sound interweaving suture technique proximally in the palm will ensure enough strength to allow immediate mobilisation. PMID- 1295108 TI - [Respiratory insufficiency--life with a respirator]. PMID- 1295109 TI - [Respiratory insufficiency--helpers in the home]. PMID- 1295110 TI - [Nursing story. Balancing act]. PMID- 1295111 TI - [French relief assistance--where are the borders?]. PMID- 1295112 TI - [New job--from nursing to photography and journalism. Interview by Lars Peter Bergqvist]. PMID- 1295113 TI - [Politics--they have talked a lot. Negotiations 93]. PMID- 1295114 TI - [Danish Nursing Council--what has become of demands? Negotiations 93]. PMID- 1295115 TI - [Ethics on the agenda. Interview by Grethe Kjaergaard]. PMID- 1295116 TI - [Respiratory insufficiency--Annette's history]. PMID- 1295117 TI - [Abnormalities of ion movements in cardiac hypertrophy and failure]. AB - Main sources of transmembrane ionic current that lead to cellular electrical activity are described. In hypertrophied myocardium, action potentials are usually markedly prolonged. Current modifications that could be responsible for this are not well established. However, despite divergent observations, one can postulate that calcium current density (current per area unit) is maintained to its normal level and that action potential lengthening can be related to a prolonged Na-Ca exchange current, a prolongation due to the lengthening of the calcium transient (systolic increase of intracellular calcium). In heart failure, calcium current appears reduced. It is markedly depressed in dilated human atria which greatly shortens action potential plateau. In cat, during the initial overload phase which triggers right ventricle hypertrophy, action potential plateau is also transiently reduced, which could correspond to an initial reduction of calcium current before its normalisation. Several effects are probably related to fiber stretch and appear to involve different types of stretch sensitive ionic channels. PMID- 1295118 TI - Approaches to experimental arrhythmias in heart failure. AB - Sudden cardiac death accounts for at least 50% of the mortality of patients with heart failure. Available clinical evidence suggests that lethal ventricular arrhythmias are responsible for the vast majority of cases of sudden death in heart failure. However, despite extensive clinical investigation over the last decade, there has been relatively little experimental study of the mechanisms underlying the development of lethal ventricular arrhythmias in heart failure. In addition to the original process leading to myocardium alterations, the role of other arrhythmogenic mechanisms such as ventricular overload and neuro endocrine activation remains to be elucidated. In ventricular hypertrophy both reentry and triggered activity may induce arrhythmias. Some studies on experimental models of heart failure did not provide consistent results concerning electrophysiological modifications and their relations with arrhythmias. Few studies in man in vivo are in favor of prolongation as well as increased dispersion of repolarisation in patients undergoing heart transplantation for idiopathic dilated cardio-myopathy. Further studies will need to be undertaken to clarify mechanisms underlying arrhythmias in heart failure. PMID- 1295119 TI - [Ventricular pro-arrhythmic effects of anti-arrhythmia drugs]. AB - Ventricular pro-arrhythmic effects of antiarrhythmic drugs correspond either to an aggravation of a pre-existing arrhythmia or to the development of a new arrhythmia not yet observed for a patient. More easily inducible ventricular tachycardias (VT) take part in this latter category. The incidence of ventricular pro-arrhythmias is difficult to evaluate but should be close to 3 to 10% during antiarrhythmic treatments. Two main mechanisms can be involved in pro-arrhythmia: 1) reentry can cause sustained VT complicating a pre-existing cardiopathy when a sodium channel blocker is prescribed, 2) early post depolarizations can result in the occurrence of torsades de pointes complicating an antiarrhythmic treatment which prolongs ventricular repolarization and QT interval. The main risk factors of pro-arrhythmia are in the first case the existence of antecedents of VT or V fibrillation with an altered ventricular function and in the second case an important prolongation of QT with bradycardia and hypokalemia. The incidence of pro-arrhythmia should decrease when these risk factors are taken into consideration. However the diagnosis of pro-arrhythmia should be systematically evoked by clinicians since these unwanted side-effects can occur with any class Ia, Ic and III antiarrhythmic drug and any drug which prolongs QT. If this diagnosis is confirmed, the need for an antiarrhythmic treatment should then be systematically evaluated in any patient taking into consideration the benefit/risk ratio of the treatment. PMID- 1295120 TI - Adverse cardiovascular effects of anti-arrhythmia drugs. Part I: Proarrhythmic effects. AB - Antiarrhythmic drugs are able to save patients from emergency dysrhythmic situations or to avoid symptomatic disorders when used in a prophylactic goal. However they can also induce adverse effects. Cardiovascular adverse effects, and especially proarrhythmic effects, are the most dreaded. Analysis of the underlying mechanisms of the onset and perpetuation of sustained arrhythmias could lead to a better understanding of causes of proarrhythmic effects and thus to a limitation of their occurrence. Antiarrhythmic drugs can modulate the three principal factors which are involved in the onset of arrhythmias: individual predisposing factors, trigger mechanisms and environmental factors. This multiparameter modulation will conduct either to suppress the arrhythmic disorders (antiarrhythmic effect) or to impair it (proarrhythmic effect). According to the numerous factors which take part in the onset and perpetuation of arrhythmia, incidence of proarrhythmic effect of antiarrhythmic drugs is very difficult to evaluate. PMID- 1295121 TI - Adverse cardiovascular effects of anti-arrhythmia drugs. Part II: Inotropic effects and specific pharmacokinetic properties. AB - The antiarrhythmic drugs are unfortunately not devoid of adverse effects. A good watching of their safety is necessary, according to their cardiovascular adverse effects which are the most dreaded. Among these and beside the proarrhythmic effects, the negative inotropic effects can impair cardiac function. Different mechanisms could explain the negative inotropic effects of antiarrhythmic drugs: reduction of adrenergic sensitivity, decrease of calcium concentration in the cardiac cells. Pharmacokinetic properties of antiarrhythmic drugs can modulate their cardiovascular adverse effects. As a matter of fact the plasmatic concentration of the unbound drug, which could be correlated to the adverse effects, fluctuates according to the protein binding of the drug. In an other way the first pass hepatic effect of a drug can be saturable so that the resulting dose-concentration curve becomes exponential. Drug disposition might also be very different from one patient to another depending on kidney and/or hepatic function and genetically determined metabolic pathways. PMID- 1295122 TI - [Study of the influence of the time of administration on the antihypertensive effect and nitrendipine tolerance in mild to moderate essential hypertensive patients. Value of ambulatory recording of blood pressure on 24 hours]. AB - Forty-one patients with mild to moderate hypertension were included in a multicentre trial. The objective was to assess the influence of the time at which nitrendipine (Nidrel 20 mg) is taken on its efficacy and tolerance. The drug was administered once daily either in the morning or in the evening during 2 consecutive periods of 28 days. Efficacy was assessed on an ambulatory recording of blood pressure over 24 hours. Globally, nitrendipine results in a statistically significant drop in blood pressure which is not influenced by the time of administration. Treatment response varies greatly according to the initial value of ambulatory diastolic blood pressure. There is a clear antihypertensive effect if ADBP is greater than or equal to 90 mmHg and no hypotensive effect if ADBP is less than 90 mmHg. The incidence of adverse effects did not vary according to the time the drug was taken. Biological tolerance was excellent. Nitrendipine, administered once daily alone appears to be an efficient antihypertensive agent, well tolerated both clinically and biologically. Its efficacy is maintained over a 24-hour period regardless of the time at which the drug is taken. PMID- 1295123 TI - [Study of the association of bladder cancer and phenacetin use. Problems set by a pharmaco-epidemiological study]. AB - In a survey of the literature, phenacetin appears to be responsible for an increased risk of urothelial tumours in humans, especially renal pelvis tumour. Few observations have suggested an association between bladder cancer and phenacetin containing analgesics however. To assess this association in France, a case-control study of bladder cancer (143 cases, 120 controls) was undertaken. We point at some methodological difficulties, such as difficulties of recall, definition of a control group, non-responses, possible French distinctive features of analgesics use. Results are not able to confirm the suspected relationship between bladder cancer and phenacetin use. PMID- 1295124 TI - [Tolerance of famotidine. Study of network of sentinel physicians in pharmaco vigilance]. AB - This paper presents the results of an intensive surveillance based on a network of general practitioners and following 200 patients treated by famotidine 40 mg per day during 6 to 8 weeks. Four patients with a previous experience of adverse reaction to another H2 antagonist did not relapse with famotidine. None interaction was reported with drugs such as beta-blockers, oral anticoagulants, theophylline, benzodiazepines, calcium antagonists. Twenty four clinical side effects were reported; For 5 patients (2.5%) the treatment had to be stopped. The most common side effects were neurological. The results are compared with those of previously published studies. PMID- 1295125 TI - [Comparison of tacrine hepatotoxicity in patients with Alzheimer disease or AIDS]. AB - Previously used in Alzheimer disease Tacrine (THA): tetrahydroaminoacridine has shown a rise of hepatic transaminase enzyme activity (TEA) in 18% of patients for Summers and 19% for Ames. Although studies using THA from USA or Canada have noticed a rise of TEA in 30% of the patients, after a treatment course with French THA we also have noted a rise of TEA in 12% of the Alzheimer patients. However, these secondary effects yielded to the end of treatment. These studies have been done with THA from different origins and different associations. Summers, the Canadian group and the French one have used THA in association with lecithin, when american group study has been made with no additional product. Therefore we have initiated a trial with oral THA in AIDS patients. 52 patients with HIV infection (26 in the IVC1 group and 26 in IVC2 group) have been treated with the same THA as the one used for Alzheimer french group. The common dosage was 150 to 200 mg (3 to 4 of 50 mg dosing capsules per day). The THA has been synthetized such as having an over 99% pureness product. After a period of 260 months/patient no elevation of TEA has been noted in any patients of our group. These results observed in HIV advanced patients with this THA are discordant with the one observed in Alzheimer's study. The dosage used in AIDS is twice higher than the one used for Alzheimer which gives us credit to the lack of hepatic toxicity in HIV advanced patient after 7 months of treatment. PMID- 1295126 TI - Characterization, self-assembly and reattachment of S layer from Clostridium botulinum type E saroma. AB - S layer of Clostridium botulinum type E Saroma and its subunits were isolated and characterized for their chemical and morphological properties. The S layer was composed of a number of subunits with apparent molecular weights ranging from about 10 to 150 kDa. The isolated S layer subunits possess the ability to assemble into recrystallized flat sheets in the absence of any supporting layer and to reattach to the cell wall from which they have been removed. Immunoblot analysis using an antiserum against whole cells of the organism showed that 60 kDa and 90 kDa subunits of the S layer were major somatic antigens of the organism. Immunogold-labeling using monospecific antiserum raised to the individual 60 and 90 kDa proteins revealed that both subunits were exposed evenly over the entire cell surface. The amino acid compositions of both subunits showed that aspartate and glutamate were predominant whereas cystine and methionine were poor. The amino acid composition and acidic property of the two subunits of the S layer agree well with the results obtained from the S layers of other bacterial species as well as other pathogenic clostridia. PMID- 1295127 TI - The characteristics of interval breast cancer in mass screening. AB - To investigate the characteristics of interval breast cancer in mass screening, comparisons were made of the following three groups: interval group (21 interval breast cancer cases), mass screening group (87 breast cancer cases detected by mass screening) and outpatient group (266 breast cancer cases diagnosed at outpatient clinics). There were no differences among the three groups in terms of the case distribution by age or obesity, but significant differences in the case distribution according to nodal involvement and tumor size. Histological grading of the malignancy of the primary tumors disclosed that the incidence of breast cancer showing frequent mitoses was high in the interval group compared to the mass screening and outpatient groups. The 7-year cumulative disease-free survival rate was 75.3% in the interval group, 90.0% in the mass screening group and 83.1% in the outpatient group. The mean tumor size of the interval cases at the time of mass screening, back-calculated on the basis of the estimated tumor doubling time, was 1.5 cm in diameter, smaller than that of the mass screening group. It is surmised that interval breast cancer is characterized by marked proliferation of the tumor cells and has a poorer prognosis than the other group cases. These findings might be due to the marked proliferation of interval breast cancer rather than because of cases having been overlooked at the time of the last screening. PMID- 1295128 TI - Radioactive cesium in dirt accumulations on the roof of buildings. AB - The concentrations of 137Cs and 134Cs in dirt deposits on the roofs of buildings are much higher than those in the surface of soil at ground level. Thus dirt on roofs concentrates radioactive cesium in fall-outs. The 137Cs concentration in dirt deposits on the roofs of older buildings is not consistently higher than that on the roofs of new ones, but the 137Cs/134Cs ratio is higher in deposits on older buildings constructed before the first half of the 1970s, and decreases exponentially with decrease in age of the buildings gradually reaching 1.9 +/- 0.2, the value in the air-borne dust at the time of the Chernobyl accident. From this relationship, the contribution of Chernobyl radioactivity to accumulated 137Cs was calculated as 32% on buildings constructed in 1962. The radioactive cesium concentrations in dirt deposits in gutters of private houses and on the roofs of university buildings in Japan were also determined. PMID- 1295129 TI - Intraarterial lymphocyte-injection therapy for lymphedema of the leg: an examination using indium-111 oxine labeled autologous lymphocytes. AB - A 58-year-old female patient with lymphedema of the left leg was treated by repeated intraarterial lymphocyte-injection therapy. To elucidate whether the injected lymphocytes act at the affected site of the leg, we examined the distribution of the In-111 oxine labeled lymphocytes injected into the proximal artery to the affected leg in comparison with the distribution in the other, healthy, leg. The radioactivity of the affected leg was almost two times higher than that of the healthy leg during the first 30 min after injection, and it remained higher even after 24 hours. The circumference of the affected leg of the patient decreased steadily during her hospital stay. These results, together with the clinical findings, suggest that some of the intraarterially-injected lymphocytes remained in the affected leg at least 24 hours and might play some role in reducing the volume of lymphedematous fluid. PMID- 1295130 TI - Two sudden death cases of idiopathic ventricular tachycardia. AB - It is said that the prognosis of idiopathic ventricular tachycardia (IVT) without organic heart disease is good in general. In this paper, two sudden death cases of IVT are reported. The first case was a 44-year-old male, who was referred to our hospital for further examination and treatment of ventricular tachycardia. Echocardiography did not show obvious organic heart disease. After the patient was diagnosed with IVT, he was given drug therapy at the outpatient clinic. However, about six months later, he died suddenly while playing mahjong late at night. The second case was a 17-year-old male. He was also referred to our hospital by another hospital after being diagnosed with ventricular tachycardia. A diagnosis of IVT was made, for which he was given drug therapy at outpatient clinic. However, the patient discontinued receiving the drug therapy. The patient died suddenly about 3 months after discontinuation of the therapy. Some idiopathic ventricular tachycardia cases have poor prognosis like the present ones. It was considered necessary to thoroughly control and guide patients with their daily life and monitor them carefully about the ingestion of anti arrhythmic agents. PMID- 1295131 TI - Unusual cases of benign stricture of the biliary tract. AB - Three patients, i.e., two adults and one child, with unusual benign stricture of the extrahepatic biliary duct are reported. Case 1 is a 63-year-old male with obstructive jaundice caused by a sclerotic vascular ring formed by the right hepatic artery and its branch. Case 2 is an 18-year-old male with obstructive jaundice due to stricture of the common bile duct caused by compression of enlarged collateral varicose veins, so-called cavernous transformation following extrahepatic obstruction of the portal vein. Case 3 is a 19-month-old boy complicated with biliary obstruction resulting from ischemic changes of the biliary duct at 10 months after extended right hepatectomy for mesenchymal hamartoma of the liver. The definitive diagnosis was made on the basis of imaging evaluations and the surgical findings. They have been free of jaundice and have shown an uneventful clinical course after the surgical interventions. PMID- 1295132 TI - A case of femoral hernia in a child. AB - A 9-year-old boy with a painless reducible swelling in the right groin was admitted to our hospital. The diagnosis of a right external inguinal hernia was made, but no inguinal hernial sac was found at operation. On further examination, the diagnosis of femoral hernia was confirmed. Radical operation for the femoral hernia was performed using McVay's procedure, and there has been no recurrence since the operation. In the Japanese literature, 25 cases of femoral hernias have been reported in children aged 1 month-9 year (average age, 4 years). The sex ratio of M:F was 2:3. Eleven cases were on the right side, 7 were on the left, and 5 were bilateral. The rate of irreducible femoral hernia was 48% (12/25 cases). Femoral hernias in children are very rare and often misdiagnosed as inguinal hernias. Correct diagnosis was made in only three cases (12%). Careful examination and awareness of the possibility of femoral hernia in children are very important when dealing with groin swelling in children. PMID- 1295133 TI - A case of concealed WPW syndrome with three different reciprocal tachycardias due to triple AV nodal pathways. AB - Triple atrioventricular nodal pathways (TAVNP) occur occasionally, but it is rare for them to produce more than two different tachycardias. Here we report a case of concealed WPW syndrome with three different tachycardias. During electrophysiologic studies, three different reciprocal tachycardias were induced. Tachycardia #1 was characterized by a cycle length of 230 msec and an A'-H interval of 70 msec. For tachycardia #2, these parameters were 300 msec and 140 msec, while they were 370 msec and 200 msec for tachycardia #3. During all three tachycardias, the earliest atrial activity was observed in the left atrium. Ventriculoatrial conduction occurred following ventricular stimulation, and the earliest atrial activity was observed in the left atrium, indicating the existence of left-sided accessory pathway. Persistence of tachycardia for 15-30 min caused marked pulmonary congestion. The heart rate was very high (260 beats/min) during tachycardia #1, and the pulmonary arterial pressure rose to 40/30 mmHg, with the pulmonary arterial diastolic pressure remaining at about 30 mmHg throughout the tachycardia. It seems that the pulmonary venous pressure rises abnormally during paroxysmal supraventricular tachycardia with a very high heart rate and that pulmonary congestion can easily occur during a short period of tachycardia. PMID- 1295134 TI - In vitro self-assembly of the S layer subunits from Clostridium difficile GAI 0714 into tetragonal arrays. AB - Regularly arrayed surface component (S layer) of Clostridium difficile strain GAI 0714 was isolated with 4 M guanidine hydrochloride from the cell wall of the organism, and examined for self-assembly in vitro. The S layer was composed of two different protein subunits with molecular weights of 32 kDa and 45 kDa. Optical diffraction analysis revealed that the morphological units of both native and self-assembled S layer were essentially identical and composed of a rhombus possessing each side of 8.1 nm and interior angle of 88 degrees. The self assembly of S layer subunits were induced in the presence of divalent cations such as Ca2+ or Zn2+, but Ba2+ or monovalent cations including K+, Na+ and Li+ failed to induce self-assembly. These results suggest that Ca+2 or Zn+2 may act as bridges to link negatively charged surface subunits. PMID- 1295135 TI - Sudden unexplained death syndrome. A review and update. AB - Sudden unexplained death syndrome (SUDS) among young healthy Thai construction workers in Singapore has been given much publicity recently. From May 1982 to July 1990, 226 SUDS were reported among them. In this article we review and compare studies on SUDS in the United States and South-east Asia. So far, studies to identify the causal factors have been inconclusive and they cannot explain the male preponderance and occurrence of death during sleep. Current hypotheses about the cause of SUDS have included stress, genetic factors, dietary deficiency (particularly thiamine), potassium deficiency, melioidosis and sleep disorders. The following areas are suggested for further research: epidemiological investigations on SUDS at its source; in-depth case studies of families with and without SUDS; role of dietary factors, biochemical studies with respect to thiamine, pyruvate and potassium metabolism in the victims and susceptibles; and histopathological studies of cases and controls. PMID- 1295136 TI - Malaria in infants whose mothers received chemoprophylaxis: response to amodiaquine therapy. AB - In October 1988, a project was implemented for assessing the malaria chemoprophylactic efficacy of weekly chloroquine (CQ) and daily proguanil (PROG) during pregnancy in Muheza-Tanzania. Resultant CQ and PROG-cohorts of infants were followed up for prompt diagnosis and treatment of malaria. Infections were primarily treated with 25 mg base amodiaquine/kg over 3 days. By September 1990, 49 and 60 infants from PROG and CQ cohorts respectively had completed one year follow up. Thirty-five (71%) infants of PROG and 44 (73%) for CQ-cohort were infected with malaria before 3 months of age. The one year mean infection episode rates were 7 (PROG-cohort) and 6.6 (CQ-cohort). Amodiaquine cleared 209 (80%) of PROG's total infections and 224 (81%) for CQ-cohort, and significantly reduced the infection load among clearance failures. Clearance failures had high pre treatment parasite densities whilst post-treatment densities were higher in the CQ-cohort than PROG-cohort. Low malaria immunity and chloroquine's long residence time could explain these differences. We conclude that early infancy malaria is common and should always be suspected, looked for and adequately treated. Amodiaquine is better than chloroquine for malaria primary therapy during infancy and early childhood. PMID- 1295137 TI - Age-related prevalence of Strongyloides stercoralis infection in Okinawa, Japan. AB - Age-prevalence of Strongyloides stercoralis infection was studied in six areas of Okinawa, Japan. In all localities, most of the infected inhabitants were aged over 40 years of age and females were less infected than males. The peak prevalence was found in inhabitants in their fifties in high endemic groups and shifted to higher age in lower endemic groups. This age-prevalence pattern resembles more that of schistosome infections than that of other gastrointestinal helminthic infections. PMID- 1295138 TI - Helicobacter pylori and dyspepsia in an Arab population. AB - To determine the incidence and significance of the detection of Helicobacter pylori in an Arab population, 116 patients with dyspepsia were studied. 89 percent of these patients had H. pylori detected by culture or/and histological definition of Campylobacter-like organisms. By the modified rapid urease test (RUT) 80% of the patients had H. pylori (sensitivity of 91%, specificity of 75%). Irrespective of the endoscopic diagnosis, the presence of H. pylori was associated with histologic evidence of gastritis. A heavy growth of H. pylori on culture was associated with active gastritis. There was no difference in the incidence rates of H. pylori with regard to various diagnoses by endoscopy. It is suggested that H. pylori may be hyperendemic among Arab patients with dyspepsia. Its presence is associated with varying severity of gastritis with or without additional endoscopically recognised findings. PMID- 1295139 TI - Comparative studies of live neonates in maternal sickle cell haemoglobinopathy in Ghana. AB - This study assessed the current status of live neonates born to sickle cell mothers when compared with those of normal (control) women. Birth weight, placental weight, fetoplacental ratio, and gestational age for live neonates in singleton births by twenty-nine haemoglobin SS (HbSS), fifty-two haemoglobin SC (HbSC), and fifty-one (normal) haemoglobin AA (HbAA) mothers were statistically compared. Neonates of HbSS mothers had a statistically lower than normal mean birth weight and gestational age, but only a shorter mean gestation significantly distinguished those of the HbSC and HbAA mothers. Inferentially, neonates delivered by HbSS women were both underweight and preterm, whereas those of HbSC women were preterm but not underweight, and apparently large for gestational age (LGA). No statistical differences were found between neonates in terms of placental weights or fetoplacental ratios. PMID- 1295140 TI - Growth and sexual maturation of Brazilian patients with sickle cell diseases. AB - Growth and sexual maturation was studied of 125 Brazilian patients with sickle cell disease whose ages ranged from 7 months to 42 years. Height and weight were significantly lower when compared with the unaffected population. The height and weight deficit increased in the age range of 11-19 years as compared with patients less than 11 years of age. Age of menarche, breast and pubic hair staging in girls, and genitalia staging and testicular volume measurements in boys indicated a delayed sexual maturation for both sexes. The comparison of adult and young patients, however, demonstrated that although puberty is delayed, a normal sexual maturation is attained later in life by most patients. PMID- 1295141 TI - A reappraisal of underlying pathology in adult patients presenting with pancytopenia. AB - An analysis of the underlying pathology and different clinico-haematological features of 202 adult pancytopenic patients is presented. Aplastic anaemia (40.6%), megaloblastic anaemia (23.26%) and acute myeloblastic leukaemia (12.8%) together accounted for most of the cases. Our aplastic anaemia cases showed several different features compared to the cases reported in western literature. Aplastic anaemia and megaloblastic anaemia patients revealed significant differences in the incidence of hepatosplenomegaly, anisocytosis, circulating erythroblasts, relative lymphocytosis (P < 0.001 for all) and reticulocytosis (P < 0.01). The present study stresses the importance of physical and peripheral blood findings in the management of pancytopenic patients. PMID- 1295142 TI - Hemoptysis in rheumatic heart disease. AB - 107 Consecutive patients with rheumatic valvular heart disease (41 males, 66 females, average age 24.2 years) being followed at an Ethiopian cardiology referral clinic were examined and questioned about their experience of hemoptysis. 51 Patients (48%) gave a history of hemoptysis; 11 described their usual hemoptysis as frank blood, 40 as blood-streaked sputum. 29 patients had frequent hemoptysis, 13 had several episodes, and 9 only 1 occurrence. Prevalence of hemoptysis did not vary significantly by sex, physical findings, New York Heart Association classification, or valvular lesion, including the presence or absence of mitral stenosis. A majority (64) had been tested for tuberculosis, with 5 having been treated for active disease. Hemoptysis is a common manifestation of rheumatic heart disease, and is usually well tolerated. PMID- 1295143 TI - Renal papillary necrosis in Kuwait. AB - In 2,158 consecutive routine urograms, 85 patients (51 males and 34 females) were found to have typical changes of renal papillary necrosis, an incidence of 3.9% (2.8% in males, 9.4% in females). The changes were bilateral in 60 patients (71.6%) and unilateral in 25 (29.4%). 3 patients were diabetics, 4 had sickle cell anaemia and 7 had obstructive uropathy. 19 patients admitted to analgesic abuse. The remaining 52 patients were idiopathic but a combination of analgesic abuse and dehydration may have been the cause in this group. The possible reasons for the high incidence of RPN especially in females in this hot desert environment are discussed. The literature on the subject is briefly reviewed. PMID- 1295145 TI - Severe falciparum malaria: survival with oral therapy. AB - A case of severe falciparum hyperparasitaemia with trophozoites in greater than 35% of the patient's erythrocytes, relative lack of clinical symptoms and no organ complication is described. The patient, a 26-month old African child, was treated with oral mefloquine with prompt clearance of fever and parasitaemia in 24 and 48 hours respectively. No untoward sequelae was observed during 75 days of periodic clinical assessment. PMID- 1295144 TI - Obstetrical condition and neonatal neurological outcome in Dominica, the Caribbean. A comparative study. AB - Risk factors during pregnancy and delivery and neurological morbidity of newborns were assessed in a birth cohort in Dominica, the Caribbean. The data were compared with two reference groups, one from Grenada, the Caribbean, and the other from Groningen, the Netherlands. Despite variations in cultural and socio economic situation, the similarities in obstetrical conditions, neonatal neurological morbidity and perinatal relationships between the three groups were more striking than the differences. The Dominican group showed a significantly higher rate of preterm births than the two other groups. Preterm birth was associated with a significant increase in neurological deviancy. In general motility and muscle tone were found to be lower in the Caribbean region than in the Netherlands. PMID- 1295146 TI - Isolation of Entamoeba histolytica from arthritic knee joint. AB - Amoebae were isolated from an arthritic knee of a male patient. The organisms grew in Egg Yolk Infusion medium, and in Diamond's Biosate Iron-Serum-33 medium, which contained Trypanosoma cruzi, and were identified microscopically as Entamoeba histolytica. Furthermore, amoebae-like organisms in aspirate and cultures were immunocytochemically identified using monoclonal antibodies against E. histolytica. On the basis of the morphologic and immunologic observations, it was concluded that the knee lesion was caused by infection with E. hystolytica. The knee lesion resolved following treatment with metronidazole. This case is the first report of an amoebic infection of the knee joint. PMID- 1295147 TI - Pasteurella multocida infection in Singapore. AB - A case of Pasteurella multocida infection in Singapore is presented. The patient was a 21-year-old Chinese male who developed fever and cellulitis with abscess formation of his right index finger after it was bitten by a stray cat. The organism was isolated in pure culture and identified as Pasteurella multocida subspecies septica. The patient responded to antibiotic therapy and had an uneventful recovery. PMID- 1295148 TI - The association of infective hepatitis type A (HAV) and diabetes mellitus. AB - The cases of three patients who developed diabetes mellitus (DM) within 2-3 weeks of acute hepatitis A virus (HAV) infection associated with diabetic ketoacidosis are reported. The ketoacidosis was considered an index of insulin dependent diabetes mellitus most likely precipitated by the acute virus infection. PMID- 1295149 TI - IgA nephropathy (IgAN) presenting with the nephrotic syndrome. AB - A 20 year old Nigerian male with the nephrotic syndrome was found to have IgA nephropathy (IgAN) on renal biopsy. The renal function at presentation was normal and his nephrotic syndrome initially responded to steroid therapy. However, significant deterioration in renal function was noticed 2 years later when his nephrotic syndrome relapsed. This is the first documented case of IgAN in a Nigerian. Considering the rather low renal biopsy rate in this environment, a number of cases with this nephropathy may be missed. PMID- 1295150 TI - A critical study into the fecal analysis routine in practice in Jordan. AB - The fecal analysis routine adopted by 21 diagnostic medical laboratories in Jordan was surveyed by the means of a questionnaire filled in by the senior year medical technology students who spent 16 weeks in these laboratories as trainees. The recommended routine fecal analysis was not completed satisfactorily by any of the laboratories surveyed. The wet mount microscopic examination was the sole technical test done for the examination of parasite and ova by the majority of the laboratories, 90% (19 of 21). None of the surveyed laboratories adopted the routine use of a concentration technique. One hundred and eight known positive stool specimens were examined by four qualified medical technologists. The wet mount technique revealed positivity in 53% of specimens only, while the formol ether sedimentation technique yielded 98-100% positivity. This indicates the value of the formol-ether sedimentation technique over the practiced wet mount technique in the routine fecal analysis. PMID- 1295151 TI - Alkohl use in Saudi Arabia. Extent of use and possible lead toxicity. AB - The extent of alkohl use, its lead content and blood lead levels after use were investigated. A total of 500 individuals were interviewed. It was observed that 233 (47%) had used alkohl. The main purposes for its use were: eye cosmetic (66%) and eye and umbilical stump remedy (26%). Of those who used it as an eye cosmetic, 45% applied it daily and 18% occasionally. Sixty-five (28%) of the users experienced some type of adverse reactions. Their mean blood lead levels was 0.99 uMol/L as compared to 0.26 uMol/L in non-users. The majority of alkohl samples analyzed had high lead content. Mean blood lead levels of rabbits treated with alkohl was 3.31 uMol/L. It is recommended that the public should be educated on the possible dangers of continued alkohl use. PMID- 1295152 TI - Prevalence of hookworm species in Pondicherry, India. AB - A study was carried out to find out the hookworm species prevalent in Pondicherry, India, based on the identification of filariform larvae recovered from coproculture of hookworm positive stools. A total of 184 hookworm positive stools were cultured using the Harada-Mori coproculture method. The results of the study for the first time showed both hookworm species, Ancylostoma duodenale (60 cases) and Necator americanus (49 cases) to be present in Pondicherry. The former species was relatively more common than the latter. Three cases were infected with both species of hookworm. PMID- 1295153 TI - [The 3-dimensional organization of the nucleolus and the nucleolus organizer regions in differentiated cells. II. The reticular, vacuolized and nucleolonemal nucleoli of hepatocytes from the intact mouse liver and of hepatocytes stimulated to proliferation as a result of partial hepatectomy]. AB - By means of stereological and morphological analysis, the dynamics of nucleolar structural changes in stimulated mouse hepatocytes has been studied. Reticulated and vacuolized nucleoli typical for normally functioning hepatocytes were shown to convert into the nucleolonemal nucleoli, first noticed 18 hours following operation. The process of activation of mouse hepatocyte nucleoli involves two steps. At the first step (within 1-18 hours following operation) a progressive growth of nucleoli volume, due to a simultaneous reduction of vacuolar sizes and growth of RNP component occurs. Such changes were observed in both groups of nucleoli being present in the intact mouse liver, because at this particular step a considerable decrease in the number of vacuolized nucleoli took place. Besides, in the stimulated hepatocyte nucleoli the number and total volume of fibrillar centers increase. However, in spite of their considerable changes, the nucleoli preserve the marks characteristic of the reticulated type. The second step of activation, noted 18 hours after stimulation of hepatocytes, includes more fundamental structural reconstructions. As the result, reticulated nucleoli obtain the nucleolonemal structure. At the same time, on the background of a further decrease in the individual volume and an essential growth of the total volume in the fibrillar centres, a spasmodic increase in the mass of the dense fibrillar component, which is associated with the formation of the continuous strand of the nucleolonema. All this is responsible for the complete changes in structural organization of nucleoli commonly seen in mouse hepatocytes. It is suggested that the cause of such a structural reconstruction may be due to the changes in topography of transcriptionally active regions of rDNA. PMID- 1295154 TI - [The 3-dimensional organization of the nucleolus and the nucleolus organizer regions in differentiated cells. III. Changes in the nature of the distribution of argentophilic proteins in the nucleoli of mouse hepatocytes with stimulation of the hepatocytes to proliferation]. AB - The stereological and morphological analysis of Ag-positive zones revealed the principal difference in quantity and distribution of Ag-NOR proteins in reticulated and nucleolonemal nucleoli of mouse hepatocytes. It is shown that reticulated nucleoli of resting hepatocytes are characterized with the presence of discrete rounded Ag-positive zones, whose quantitative parameters correspond to the fibrillar centers and dense fibrillar component taken together. The analysis of the three-dimensional structure of Ag-positive zones of nucleolonemal nucleoli has revealed considerable changes in quantity and distribution of Ag-NOR proteins due to proliferative stimuli. 22 hours following operation, a continuous, strongly winding strand of nucleolonema is revealed in the nuclei. Taking into account that Ag-NOR proteins are associated with the transcriptionally active regions of rDNA it may be suggested that this structural conversion was due to decondensation and activation of inactive regions of r chromatin. A considerable growth of Ag-positive zone volume during the conversion of reticulated nucleoli into the nucleolonemal type may be explained by the increase in Ag-NOR protein contents. PMID- 1295155 TI - [The molecular organizational characteristics of the cell nucleus components at different phases of the mitotic cycle and in the resting state]. AB - Data about the changes of the cell nucleus structure at different levels of its organization are summarized in the review. The data about the change of the DNA break number during the cycle and in resting state are presented and the role of the changes of the repair efficiency in this process is discussed. The changes of the chromatin protein spectrum, the chromatin structure at nucleosomal and supranucleosomal levels, the DNA superhelicity, topoisomerase activity, nuclear matrix composition and structure are discussed as well. The nucleus structure during the S-phase and mitosis and the cycle-related changes of the chromatin structure in lower eukaryotes are reviewed separately. PMID- 1295156 TI - [The regulation of the DNA repair process in mammalian cells. IV. The role of DNA polymerases in the epidermal growth factor regulation of the repair of single stranded DNA breaks induced by ionizing radiation in Swiss 3T6 mouse cells]. AB - A study was made of the repair of ionizing radiation-induced DNA single-strand breaks (SSB) in proliferating and quiescent mouse Swiss 3T6 cells and in those stimulated from the quiet status by epidermal growth factor in combination with insulin, in the presence of specific inhibitors of DNA polymerase alpha and delta (aphidicolin) and DNA polymerase beta (2', 3'-dideoxythymidine-5'-triphosphate). The repair of DNA SSB induced by X-ray-irradiation (10 Gr) or by gamma-ray irradiation (150 Gr) is more sensitive to aphidicolin independently of cell proliferating status. Aphidicolin inhibits the recovery of single-strand DNA in quiescent and mitogen-stimulated cells three times stronger than in proliferating cells. The influence of 2', 3'-dideoxythymidine-5'-triphosphate on the rate of DNA SSB repair in cells of all the three types does not differ. Thus, the decrease in DNA repair efficiency in quiescent cells is connected with a decrease in the activity of aphidicolin-sensitive DNA polymerase, apparently DNA polymerase alpha. It is suggested that the regulation action of mitogens on the DNA SSB repair may be determined by qualitative changes of this enzyme or of some conditions in which it functions. The involvement of DNA polymerase delta in this process is not excluded. PMID- 1295157 TI - [Ethics confronted with new medical scientific data]. PMID- 1295158 TI - [Impotency. Review of etiopathogenesis]. PMID- 1295159 TI - [Treatment of acute and bacterial lower respiratory tract infections with roxithromycin]. PMID- 1295160 TI - [Pyogenic brain abscess: study of 16 cases]. PMID- 1295162 TI - [Epilepsy and psychiatric disorders. Retrospective study over five years]. PMID- 1295161 TI - [Eye involvement in AIDS: the first 12 Tunisian cases]. PMID- 1295163 TI - [Alpha-thalassemia in the north-east of Tunisia: three cases of hemoglobinopathy H]. PMID- 1295164 TI - [Leiomyosarcomas of the inferior vena cava: two cases]. PMID- 1295165 TI - [Pregnancy and epilepsy. Management]. PMID- 1295166 TI - [Urethral strictures. 158 cases]. PMID- 1295167 TI - [Results of transluminal coronary angioplasty. 42 patients]. PMID- 1295168 TI - [Digestive tract involvement in systemic scleroderma]. PMID- 1295169 TI - [Hepatic tumors in children. Anatomo-pathological study in 35 cases]. PMID- 1295170 TI - [Efficacy and tolerance of pefloxacin in the treatment of complicated urinary tract infections in Tunisia]. PMID- 1295171 TI - [Penicillin resistance in neisseria gonorrhoeae]. PMID- 1295172 TI - [Castleman's disease-multicentric form. A case report]. PMID- 1295173 TI - [Ferritin: structure, metabolism and clinical value]. PMID- 1295174 TI - [Percutaneous treatment of a primary psoas abscess]. PMID- 1295175 TI - [Hysteroscopy and hysterosalpingography: which examination to choose?]. PMID- 1295176 TI - [Involvement of the eyelids and the lacrymal system in facial burns]. PMID- 1295178 TI - [Cutaneous sarcoid reaction in tattoo scars: four cases, two with systemic involvement]. PMID- 1295177 TI - [Diagnosis and medical treatment of kidney abscess: nine cases]. PMID- 1295179 TI - [Umbilical endometriosis: a case report]. PMID- 1295180 TI - [The modification of posterior sclerocyclostomy in treating ciliochoroidal detachment after glaucoma-control operations]. PMID- 1295181 TI - [A glutathione deficiency in open-angle glaucoma and the approaches to its correction]. AB - A total of 151 patients with open-angle glaucoma, 23 ones with closed angle glaucoma, and 57 ones with age-associated cataracts were examined. The reference group consisted of 21 subjects with posttraumatic cataracts (1.5 years after the injury) and normal subjects. Nonprotein sulfhydryl groups (glutathione) were measured in the peripheral blood, aqueous humor, and in tissue samples from the scleral drainage sites, obtained in antiglaucoma surgery and in surgery for cataract extraction. Aqueous humor of patients with posttraumatic cataracts, blood samples of these patients and normal subjects were examined for control. The level of sulfhydryl groups was found significantly lowered in the anterior chamber humor of patients with open-angle glaucoma, particularly in those with disease Stages II and III as against the controls. The content of sulfhydryl groups was lowered in the tissue samples from the scleral drainage area of patients with open-angle glaucoma Stages II and III vs. that in the patients with Stage I condition. Similar changes were found in the red cells of patients with Stages II and III open-angle glaucoma. Glutathione is an important component of the cellular antioxidant system. The findings point to a reduction of the processes of antioxidant defense of ocular tissues, developing as early as in the first stage of open-angle glaucoma. Lipoic acid administration for 2 months was associated with a rise of glutathione level in the red cells of patients with Stages II and III open-angle glaucoma. PMID- 1295183 TI - [The use of new scleroplastic materials in the surgery of traumatic retinal detachment]. AB - New textile-based material is suggested for scleroplastic surgery for detachment of the retina. Features of the design of the new material are described and the efficacy of the implants assessed. Textile-based implants are recommended for clinical practice. PMID- 1295182 TI - [Transcutaneous electrostimulation of the primary elements of the visual system in children after the extraction of a congenital cataract]. AB - Courses of transcutaneous electrostimulation of the visual analyzer periphery according to E. B. Kompaneets were administered to 31 children (56 eyes) aged 4 to 12 because of low vision acuity after congenital cataract extraction. The amplitude of stimulating pulses was from 150 to 400 microA. The first course consisted of 5-8 sessions, repeated courses of 4 sessions. The results were assessed by vision acuity check-ups and recordings of visual [correction of auditory] evoked potentials (AEP). Vision acuity improved from 0.1 to 0.9 after a course of treatment. AEP amplitude was reduced in all the patients to 15.4 microV on an average, the time of the pulse conduction in the auditory system was normal (113.2 ms). Electrostimulation effects on the AEP were negligible. Electrostimulation may be recommended to children with low vision acuity and low values of the AEP amplitude after congenital cataract extraction. PMID- 1295184 TI - [The dynamic indices of local blood circulation in the surgical treatment of retinal detachment]. AB - The hemodynamics of both eyes was examined before and after surgery in patients with detachment of the retina. The depression of uveal blood stream was transitory in extrascleral ballooning, in contrast to that in cerclage and filling, when the hemodynamic characteristics of both eyes are significantly reduced. PMID- 1295185 TI - [The hemodynamics of the brain and eye in patients with presenile and senile nonexudative central chorioretinal dystrophy during health resort treatment]. AB - Rheographic studies of the cerebral and ocular hemodynamics carried out in patients with presenile and senile nonexudative central chorioretinal dystrophies over a 26-day course of multiple-modality health resort treatment revealed left side asymmetry of the earlier and more marked injuries of the ocular membranes and the carotid system, a low rheographic index of the carotid system as early as in the first stage of the disease. The findings evidence improvement of the brain and eye hemodynamics in the course of treatment, this being conducive to improvement of the ocular function during all stages of the disease. The most dynamic parameters were the rheo-ophthalmographic coefficient in the patients with all stages of the disease and the rheographic index of the central cerebral artery in those with Stages I and II maculodystrophy. Assessment of these parameters in the course of health resort therapy of the retinal conditions mentioned will help assess the treatment efficacy. PMID- 1295186 TI - [The effect of trental and actovegin on the organs of vision when administered into the end periorbital branches of the ophthalmic artery (experimental research)]. AB - Specific features of the delivery and the possible side affects of intraarterial infusions of trental and actovegin on the retina, vessels, and the optic nerve in administration of these drugs into the peripheral periorbital branches of the orbital artery were under study. Contrast angiography and fluorescent angiography have confirmed in all the cases the correctness of the catheter position and its functional competence, as well as the possibility of rapidly creating the necessary concentration of the drugs in the retinal and choroidal vessels for a sufficiently long time. Electroretinogram recording before and after intraarterial infusions of the before drugs has demonstrated the functional intactness of the retina, and morphologic studies have shown the absence of any injurious effect of the drug on the organ of vision in such a method of administration. Results of experimental trials permit recommending starting the clinical trials of the intraarterial infusion of trental and actovegin into the periorbital branches of the orbital artery. PMID- 1295187 TI - [The immunological factors characterizing neurochorioretinitis]. AB - Comprehensive clinical and immunologic studies carried out in 38 patients with neurochorioretinitis have demonstrated the contribution of infection to the etiology and pathogenesis of this condition and helped identify the nature, mostly infectious, of the condition in 55.3% of patients. Toxoplasma infection, revealed in 39.5% of cases, is one of the major etiologic factors of neurochorioretinitis. Tuberculous etiology of the condition is more rare (7.9% of cases). The autoimmune systemic component was detected in 7.9% of the examinees. Immunopathologic shifts, presenting as hyperimmunoglobulinemia, were fairly frequent (71.9% of patients), excessive concentrations of circulating immune complexes were detected in 78.6% and cryoglobulins were found in 42.9% of the examinees, this permitting the authors to regard neurochorioretinitis as a form of immunocomplex conditions of the eye, most possibly, of an infectious origin. Blood group A (II) was found to be a risk factor for neurochorioretinitis patients; according to the literature data, this is explained by a reduction of the interferonogenic activity. Etiotropic anti-inflammatory drugs, including corticosteroids, and interferon preparations for the risk group patients appear to be advisable for the therapy of neurochorioretinitis. PMID- 1295188 TI - [Panoramic zonography in the diagnosis of orbital fractures]. AB - A total of 453 patients with acute injuries of the upper and median zones of the facial skull were examined. The most frequent injury was that to the orbital entrance, fractures of the inferior wall; fractures of the exterior, interior, and anterior walls were less incident, and fractures of the orbital apex were the most rare. Types of the skull bone fractures, associated with injury to the orbital walls, were distinguished. The x-ray semeiotics of injuries to the orbital walls was specified making use of panoramic sonography. Panoramic zonography [correction of sonography] with the use of the Zonark [correction of Sonarc] apparatus helps identify the volume and extension of the injuries on all the orbital walls and is altogether an effective method for the diagnosis of the orbital wall fractures. PMID- 1295189 TI - [The involutional vitreoretinal syndrome]. AB - Ocular changes in elderly subjects are described, that may be regarded as manifestations of a disease, denoted by the author as the involution vitreoretinal syndrome. The subjective signs of the syndrome are floating 'moths', photopsias presenting as a 'lateral lightning', sudden appearance of a central macula (central positive scotoma). The objective signs are destruction and posterior detachment of the vitreous body, peripheral retinal dystrophy, stable light reflexes (coin-shaped, flap, etc.) on the fundus oculi, previously described by the author. The syndrome complications are fibroplasia of the fundus oculi central area, macular edema, perforation of the macula and characteristic lenticular changes. The author singled out the cases with combined changes of the vitreous body, fundus oculi and lens involvement as a lentivitreoretinal form of the involution vitreoretinal syndrome. PMID- 1295190 TI - [The dependence of the cortical topography of visual evoked potentials on the stimulation frequency]. AB - Cortical topography of steady-state flash visual evoked potentials (fVEP) was compared with topography of transient fVEP and pattern VEP (pVEP) in 17 normal subjects. It was found that at low (up to 20 Hz) frequencies fVEP demonstrate extensive dissemination on the scalp. At higher frequencies (30 Hz or higher) fVEP were registered mostly in the occipital area similarly as transient pVEP. These results suggest that the neural structures responsible for the generation of transient pVEP and steady-state fVEP of 30 Hz and higher frequencies are anatomically identical. PMID- 1295191 TI - [Pathological mineralization in retinoblastoma]. AB - Calcium phosphate, fluoroapatine mineral, Ca5(PO4)3F, characterized by a strong reflex in interplanar distance d = 2.789 A, were identified in the tissue of retinoblastoma by x-ray destructive analysis. The strong reflex intensity and the respective fluoroapatite level in the tumor are the higher, the more malignant the tumor is. The malignancy degree is determined by histologic analysis of the tumor cellular composition after enucleation. PMID- 1295192 TI - [A method of calibration measurement in assessing the hemodynamics of the retinal vessels]. PMID- 1295193 TI - [The laser correction of recurrent elevated intraocular pressure after a surgical operation to control glaucoma complicated by the blocking of the postoperative fistula by the root of the iris]. AB - Laser intervention was carried out in 18 patients (18 eyes) with open-angle glaucoma and decompensated intraocular pressure, that developed in 2 weeks--5 years after primary antiglaucoma surgery. Developed glaucoma stage was diagnosed in 16 eyes, in 2 eyes far-advanced condition was found. Blocking of the fistula by the iridal root was responsible for the inefficacy of fistulizing surgery. Laser trabeculoplasty to compensate for the intraocular pressure was carried out in 18 eyes, in 9 eyes this treatment was combined with gonioplasty. Stable normalization of intraocular pressure was observed in 13 eyes in remote periods after laser coagulation. Analysis of the results has brought the authors to a conclusion that the administered laser trabeculoplasty as an individual treatment modality and in combination with gonioplasty is fairly effective, results in prolonged compensation of the ophthalmic tone, and is altogether less traumatic than repeated surgery. PMID- 1295194 TI - [Ocular function in beta-thalassemia patients]. AB - The eyes were examined in 118 inpatients with various thalassemia forms. The examinations included viso- and perimetry, biomicro- and ophthalmoscopy, fluorescent angiography of the fundus oculi and retinophotography. Patients with thalassemia were found to develop a variety of changes in the eye, whose manifestations depended on the length and severity of the underlying disease and on the treatment administered. Changes in the conjunctival and retinal vessels develop as early as in the initial stages of thalassemia, presenting as twisting, dilatation, and irregular calibre of the veins, dilatation of the arteries and reduction of their light reflex. Later dystrophic and atrophic changes develop: obliteration of the iris pattern and thinning of its peripheral zone, deterioration of blood circulation in the central retinal zone. Multiple blood transfusions and hemosiderosis lead to the development of hyperpigmentation of the limb, sclera, fundus oculi and appearance of retinal angioid strips. These findings should be taken into consideration when assessing the ocular status of thalassemia patients and defining the indications for treatment for angiopathic and dystrophic processes in the eye. PMID- 1295195 TI - [The clinico-morphological characteristics of the annular form of iridociliary neoplasms]. AB - The authors present the results of clinical and morphologic analysis of 10 cases with annular iridociliary tumors that occurred within the latest decade. The incidence of this tumor among other intraocular tumors has been 3.7%, that among iridocialiary tumors, 42.8%. In seven of the ten patients the disease manifested by elevation of intraocular pressure, less frequently it manifested by changed color of the iris or acute iridocyclitis. Extrabulbar tumor growth into the scleral conjunctiva was observed in half of the patients, in two of these lymphogenic metastases were detected. The prolonged latent course of the disease impeded in the majority of cases not only timely diagnosis of the intraocular tumor, but of its dissemination as well. Four histologic variants of the tumor growth were distinguished. PMID- 1295196 TI - [Visual evoked potentials: the theoretical bases and principles for the practical use of the method in the eye disease clinic]. PMID- 1295197 TI - [The intravascular irradiation of the blood: its clinical efficacy and the prospects for its use in ophthalmology]. PMID- 1295198 TI - [The optimization of a method of local anesthesia in glaucoma-control operations]. AB - Revising his own experience, the author comes to a conclusion that instillation and subconjunctival anesthesia is sufficient for painless antiglaucoma surgery. Retrobulbar anesthesia and eyelid akinesia are justified only in rare cases. Use of the bridle suture is indicated only for surgery of the patients with a narrow lid slit and deeply sunk eyeball. PMID- 1295199 TI - [The influence of the fixation of the scleral flap on the hypotensive effect of trabeculectomy]. AB - The author analyzes 60 trabeculectomies with fixation of the superficial scleral flap by three nodular sutures (n = 24) and by one nodular suture (n = 36). He comes to the conclusion that trabeculectomy with scleral flap fixation by one nodular suture is preferable to its fixation with three sutures, for it creates better conditions for the formation of filtration pad and provides a more stable hypotensive effect, as evidenced by the results of three-year follow-up (75% vs. 41.6%). Nonetheless the author claims that fixation of the scleral flap with 3-4 sutures is desirable in cases when filtering trabeculectomy variants are deliberately employed or when trabeculectomy modifications with uveoscleral discharge stimulation are used. PMID- 1295200 TI - [Excessive cicatrization after glaucoma-control operations: the participation of plasma fibronectin]. AB - Based on the results of examinations of 300 patients with primary glaucoma after trabeculectomy, the author has developed clinical criteria for the evaluation of the intensity of the reparative processes at the site of intervention. Plasma fibronectin levels were found to grow with the progress of glaucoma (from Stage I to Stage II almost twofold). Analysis of correlations and regressions has revealed reliable relationships between plasma fibronectin levels and clinical values of the intensity of reparative processes at the site of surgery. Preoperative measurements of plasma fibronectin help predict with a high degree of probability the hypotensive effect of surgery. PMID- 1295201 TI - Normal values for certain serum enzymes of clinical value in Indian elephants. PMID- 1295202 TI - Causes of lamb morbidity and mortality in the Ethiopian highlands. AB - A study was conducted to investigate causes of lamb morbidity and mortality on farms and on-station at Debre Berhan during 1989 and 1990. It showed pneumonia (bacterial and/or verminous), starvation-mismothering exposure (SME) complex, gastrointestinal parasites, enteritis, abomasal impaction and physical injuries to be important health constraints on productivity. Neonatal mortalities were 51.5% and 46.3% on farms and on-station respectively and occurred owing to management problems such as SME, abomasal impaction and physical injuries. On the farms the lamb birth weight was 2.56 +/- 0.25 kg and was significantly (p < 0.05) affected by the dam's age, lambing weight, litter size, sex of lamb and year of lambing, but not by the season of lambing. Birth weight significantly (p < 0.05) influenced lamb mortality. Lambs with a low birth weight tended to die from SME. Morbidities and mortalities due to infectious causes increased in older lambs, suggesting that infections were acquired with age when resistance was lowered owing to inadequate nutrition and poor management. Heavy loss of lambs could be overcome by such health management interventions as foster mothering, warming lambs during the cold season and vaccination with polyvalent vaccines against pasteurellosis, clostridial infection and Dictyocaulus filaria. PMID- 1295203 TI - The effect of repeated freezing and thawing of serum on the activity of antibodies. PMID- 1295204 TI - Controlling tick infestations and diseases in sheep by pour-on formulations of synthetic pyrethroids. A field study. AB - The use of synthetic pyrethroids in pour-on formulations reduced tick infestations and the incidence of tick-associated diseases in lambs more than dipping in organophosphate acaricides. Though the use of pyrethroids did not prevent the lambs from being infected with tick-borne fever (TBF), the incidence of lambs with lameness (tick pyaemia) or lambs suddenly found dead (Pasteurella haemolytica septicaemia), which often are seen in association with TBF, was reduced. The use of pyrethroids for three years did not seem to affect the prevalence of TBF. PMID- 1295205 TI - Helminths of sheep and goats in desert areas of south-west Mauritania (Trarza). AB - Faecal samples were obtained from sheep and goats before, during and after the rainy season at three locations in south-west Mauritania. Several animals were also necropsied at the same time. Haemonchus contortus was the most prevalent worm. Infection by digestive-tract strongyles and Strongyloides papillosus was always very light (prevalence less than 20%). Sheep were more heavily infected than goats but animals under 1 year of age were not infected by digestive-tract strongyles. It is likely that young small ruminants became infected during the rainy season and that the parasites so acquired are inhibited in their development and/or survive nearly one year as adults. PMID- 1295206 TI - The effect of peri-parturient anthelmintic treatment on the productivity of dairy cattle in subtropical western India. AB - Trials with fenbendazole (Panacur, Hoechst India Ltd) were carried out on two commercial farms in subtropical western India to study the response and economics of nematode treatment in adult dairy cows. Milk yield, lactation length, time to first oestrus and worm egg output were monitored in treated and control groups. Treatment reduced the egg count considerably. Treated cows produced 142 litres more milk over 100 days (p < 0.05), with extension of lactation length and advancement of time to first oestrus. The economic gain in terms of milk yield far outweighed the cost of anthelmintic used. PMID- 1295207 TI - Endotoxin-induced microvascular injury in isolated and perfused pig lungs. AB - The lungs of 13 healthy Landrace piglets were isolated, perfused and maintained in an isogravimetric state under zone III conditions. By applying vascular occlusion methods, the total blood flow resistance (Rt) was partitioned into four components: arterial (Ra), pre- (Ra') and post-capillary (Rv'), and venous (Rv). The capillary filtration coefficient (Kfc) was evaluated using a gravimetric technique. A bolus of 55 micrograms of Escherichia coli endotoxins (LPS) per 100 g of lung was injected into the arterial reservoir of eight lungs, followed by an infusion of LPS at a rate of 55 micrograms per 100 g of lung per hour for 180 min. A bolus of theophylline (85 mg per 100 g of lung weight) was injected into the arterial reservoir after the last determination of the Kfc value. All the parameters were evaluated again when the lungs reached a new steady state. Endotoxin induced a significant increase in Rt from 54.7 +/- 7.0 at zero time to 184.7 +/- 44.2 cmH2O min L-1 (100 g)-1 180 minutes later, which can be ascribed to the increase in Ra' and Rv'. These haemodynamic modifications were related to the increases in the arterial pressure and in the pressure at the distal end of the arterial segment and to the decreases in the pressure at the proximal end of the venous segment and in the blood flow. The capillary pressure and the lung weight remained unchanged. Endotoxin infusion induced an increase in the Kfc value from 0.208 +/- 0.011 (at t = 0) to 0.391 +/- 0.034 ml min-1 (cmH2O)-1 (100 g)-1 (at t = 180). Administration of theophylline significantly reduced Rt,Ra,Ra' and Rv' towards or under the baseline values and also induced a significant increase in the lung weight and in the Kfc value. It was concluded that the endotoxin-induced increase in the total blood flow resistance can be ascribed to a vasospasm occurring at the level of the pre- and post-capillary small vessels and that changes in the permeability of the endothelium greatly contribute to the development of the pulmonary oedema observed in endotoxaemic pigs. PMID- 1295208 TI - [Studies of tissue endoproteases determining viral tropism]. PMID- 1295209 TI - [Exchangeability of HIV/SIV regulatory genes]. PMID- 1295210 TI - [Pathogenic mechanism of virus infection mediated by host response: important role of host-dependent oxygen radical generation]. PMID- 1295211 TI - [The use of biologically active plant substances for accelerating the process of climatic adaptation on arrival at a health resort]. PMID- 1295212 TI - [The effect of decimeter waves on the metabolism of the myocardium and its hormonal regulation in rabbits with experimental ischemia]. AB - Biochemical and morphometric methods were employed to study the effect of decimetric waves (460 MHz, 10 and 120 mW/cm2) in cardiac and thyroid exposure on oxygen metabolism, myocardial microcirculation and contractility, thyroid and adrenal hormonal activity, kallikrein-kinin system activity in rabbits with experimental myocardial ischemia. Hypoxia discontinued in all the treatment regimens, but the exposure of the heart (field density 10 mW/sm2) had the additional effect on lipid peroxidation which reduced in the serum and normalized in the myocardium, on myocardial contractility, kallikrein-kinin system and on the adrenal and thyroid hormones. PMID- 1295213 TI - [Carbon dioxide baths in the early prevention of hypertensive and ischemic heart diseases in adolescents with arterial hypertension and a hereditary predisposition to these diseases]. PMID- 1295214 TI - [The use of sea mud in the combined therapy of patients with acute pneumonia at a hospital]. AB - Basing on the observation on 246 patients with acute pneumonia, it is inferred that application of mud can be beneficial since the hospital treatment day 4-5. Compared to conventional, combined treatment with application of mud seems more favourable permitting more rapid attenuation of clinical symptoms and DIC syndrome, promoting active enzyme fibrinolysis and antithrombin-III, x-ray infiltration disappeared 4 days earlier, respiratory reserves and forced expiration grew. PMID- 1295215 TI - [The optimization of the treatment of patients with chronic bronchitis at climate health resorts]. AB - The system of staged rehabilitation of chronic bronchitis (CB) sufferers implies a sanatorium treatment stage involving climate, exercise, physical, psychological treatments, etc. In search for higher efficiency of sanatorium treatment, the analysis has been made of the response achieved in 6333 CB patients treated in sanatoria situated in various regions of the country. For all the climate conditions CB patients in remission proved the best responders. A therapeutic potential for such patients lies in better pretreatments preparation and appropriate choice of the patients in local outpatient departments, an individual approach to the diagnosis and treatment policy in sanatoria. PMID- 1295216 TI - [The general principles of the therapeutic and prophylactic use of physical factors]. PMID- 1295217 TI - [The balneotherapy importance of the silicon compounds in siliciferous waters when used externally]. AB - Bath therapy was assigned to 300 patients with primary hypothyroidism, chronic venous insufficiency of the legs, neurologic symptoms of lumbar osteochondrosis. Fresh, siliceous, siliceous carbon-dioxide and carbon-dioxide waters were tested comparatively. It is reported that siliceous baths with threshold silicon compounds concentration 50 mg/l had the effect similar to that of fresh-water baths. Indications have been specified for introduction of carbon dioxide and siliceous carbon dioxide baths in the diseases studied. PMID- 1295218 TI - [The effect of the naphthenic hydrocarbons of naphthalane on the change in the permeability of biological membranes after ionizing radiation]. AB - Nephthene hydrocarbons, a naphthalan active component, were tried for ability to change permeability of erythrocytic and vascular membranes for dyes. It was established that this preparation can return to normal hyperpermeability of biological membranes induced by radiation. Its mechanism of action is suggested to be participation in biosynthesis of adrenal steroid hormones and activation of some enzymatic systems. PMID- 1295220 TI - [Physical factors in the treatment of chronic enterocolitis in children]. AB - It is a review of long-term investigations in the field of treating chronic enterocolitis in children admitted to Pyatigorsk sanatoria. The disease is proposed to be managed with different therapeutic factors: sinusoidal currents, mud, radon, oral mineral water. Such combination proved beneficial as it corrected the principal pathogenetic mechanisms of chronic enterocolitis: inflammation, dysbacteriosis, malabsorption syndrome, enzymatic defects, etc. PMID- 1295219 TI - [The action of dynamic amplipulse therapy on the urodynamics of the upper urinary tract in patients with kidney and ureteral stone fragments following extracorporeal shockwave lithotripsy]. AB - Experimental data demonstrate that sinusoidal modulated currents are capable of increasing the frequency and amplitude of smooth muscle biopotentials in animal ureter. Basing on these findings, the authors conducted stone fragments elimination from the upper urinary tracts of patients subjected to pulse lithotripsy by means of an original physiotherapeutic complex: oral mineral water, sodium chloride baths, dynamic amplipulse therapy with 3-4 electrodes pairs applied on the renal area and different ureteral regions. The stones passage from the upper urinary tracts was reported in 91.7% of the cases. Functional improvement in the affected kidney is attributed to the stone elimination and antiinflammatory action of the above balneotherapeutic complex. PMID- 1295221 TI - [The effect of cryo- and cryoelectrotherapy on regional hemodynamics in coxarthrosis patients]. AB - Physiotherapy (cryo-, cryoelectrotherapy or sinusoidal modulated currents) and therapeutic exercise were included in the course of rehabilitation given to 110 coxitis patients. Less pronounced reduction in microcirculation in the cooled tissue was registered in the exposure to a single cryoelectrotherapy procedure than to a single cryotherapy one, activation of the blood flow that followed was more intensive. Positive trends in the local and peripheral circulation were more evident after cryo- or cryoelectrotherapy. PMID- 1295222 TI - [The therapeutic action of the low-water bulk of therapeutic sea mud]. AB - Clinical and laboratory investigations were carried out in 404 patients with rheumatoid arthritis and 205 with osteoarthrosis deformans, treated either with low-water curative sea mud mass, native sea mud or with combined mud and radon bath treatment. It was found that reducing the water content of Haapsalu sea mud did not essentially influence the therapeutic effect, in consequence of which the low water curative sea mud mass may be successfully used in the treatment and rehabilitation of various patients. PMID- 1295223 TI - [Analytical and experimental methods of determining and the significance of heat flow to the body from skin mud applications]. AB - The paper describes mathematical and experimental methods estimating heat supply to the body from peloid applications. Rat experiments provided evidence on correlation between the energy supplied and body response in the form of alterations in heat generation and heat transfer. PMID- 1295224 TI - [The assessment of the changes in the function of the cardiorespiratory system as a result of the sanatorium-health resort treatment of patients with neurocirculatory dystonia]. PMID- 1295225 TI - [Ultrastructural changes in the myocardium under the action of the helium-neon laser and obzidan]. PMID- 1295226 TI - [The treatment of the pain syndrome with radon water procedures and at a therapeutic adit in the Gastein valley]. PMID- 1295227 TI - [The predisposition of the adolescent nervous system for injury by physical loading]. PMID- 1295228 TI - [The estimation of the microclimate in organizing climatotherapy at health resorts in the southern Far East]. PMID- 1295229 TI - [Local sanatoria and their place in the system of the sociomedical rehabilitation of the rural population]. PMID- 1295230 TI - [Usefulness of biochemical studies in EPH gestosis]. AB - EPH-gestosis, especially its serious clinical complications, poses a high threat for the mother and fetus. The aetiology of this condition has not yet been completely explained. During gestosis the kidneys are most frequently involved, although other organs show changes also. The consequence of renal changes is reduction of renal blood flow and glomerular filtration rate. The studied group comprised 96 women with gestosis with at least two signs treated at the Department of Pathological Pregnancy, WAM in the years 1986-1988. The control group included 52 healthy pregnant women. Serum levels were determined of urea, creatinine-uric acid and protein. The obtained results were subjected to statistical analysis by Student's t test, accepting p less than 0.05 as statistically significant. In the group with EPH-gestosis, as compared to the control group, the uric acid level was significantly raised, while that of protein in the serum was slightly decreased. The levels of creatinine and urea were not significantly different between these groups. The raised serum uric acid level in gestosis cases was correlated with a higher frequency of instrumental labours and worse condition of the newborns at birth. PMID- 1295231 TI - [Pregnancy, labor risk factors and neonatal mortality]. AB - In 173 newborns dying at the Neonatology Department, Silesian Medical Academy in Katowice the risk factors connected with pregnancy and labour were analysed. The method used was analysis of onsterric cards and history of newborn development. In 67.3% of cases the newborns were born after complicated pregnancy and 39.9% after complicated labour. PMID- 1295232 TI - [Pregnancy and labor in multiparae]. AB - The course of pregnancy, labour and puerperium was analysed in 53 women in labour for the fifth time or more. It was found that many multiparae came from the lowest socioeconomic class and only rarely visited maternity clinics, as compared to the control group of 96 primigravidae and primiparae. They had more frequently earlier termination of pregnancy, premature rupture of membranes, and after labour incomplete placental expulsion and urinary tract infections were more frequent in them. The newborns in this group were more often stillborn or had low Apgar score. PMID- 1295233 TI - [Psychological aspects of the treatment of children with terminal renal failure by repeated hemodialysis]. AB - Adaptation difficulties of adolescents during treatment with repeated dialyses are discussed. Emotional status was studied in 5 such cases. In all of them long standing mood depression was found. The necessity of systematic psychotherapeutic care in such cases is stressed. PMID- 1295234 TI - [Current views on the treatment of hypertensive crises]. PMID- 1295235 TI - [The role of antiglobulin antibodies in pathophysiology of various internal diseases]. AB - Antiglobulins are a heterogenous group of antibodies specific for a large number of antigenic determinants on the heavy chains of various classes and on light chains. They are capable of reacting with hidden antigenic determinants of gamma globulins after they have been exposed by the action of proteolytic enzymes or after antigen-antibody reaction during which changes occur in the spatial configuration of the Fc fragments of immunoglobulin causing that they assume immunogenic properties. Antiglobulin antibodies against episomes in the Pab fragment of other antibodies have a strong regulatory influence on the immune response in view of their ability of specific interference with the response to a specific antigen. Antiglobulin antibodies may exert a protective effect but also a pathogenic effect. The latter has been demonstrated in atopic diseases, in IgA glomerulonephritis, in rheumatoid arthritis, in infectious mononucleosis, cryoglobulinaemia, in patients with IgA deficiency associated with presence of antiglobulin antibodies to IgA after transfusion of plasma or intravenous infusion of gamma globulins containing IgA. PMID- 1295236 TI - [Secondary polycythemia as an example of the paraneoplastic syndromes]. AB - The modern views on the coexistence of secondary polycythaemia with benign and malignant tumours of varying origin are reviewed describing certain mechanisms determining this association. The diagnostic management of secondary polycythaemia is outlined calling attention to the necessity of ruling out coexistence of a neoplasm. PMID- 1295237 TI - [Sudden infant death syndrome (SIDS)]. PMID- 1295238 TI - [Nephrotoxic effect of gentamicin on the function of the proximal tubules of the nephron and glomerular filtration]. AB - The purpose of the study was assessment of gentamicin nephrotoxicity with reference to proximal tubule function and glomerular filtration. The study was carried out in 20 patients with nephrolithiasis and chronic pyelonephritis, and 33 patients with respiratory and bile tract infections treated with gentamicin in doses of 2-3 mg/kg/2 h. In 3 patients with nephrolithiasis and chronic pyelonephritis signs of increased nephrotoxicity of gentamicin (according to Schentag criteria) were found. Similar signs were demonstrated in 3 patients with non-urinary tract infections. The abnormalities included increased excretion of low-molecular protein and beta-2-microglobulin (B2m), reduction of B2m reabsorption and lower glomerular filtration. Beta-2-microglobulinuria increase precede by 4-5 days the fall of the glomerular filtration rate which suggests that beta-2-microglobulinuria assessment is an early sign of gentamicin neurotoxicity. PMID- 1295239 TI - [Hemolytic anemia caused by excessive use of analgesics]. AB - A 40-year-old female patient is reported who gave a history of analgesics abuse (phenacetin) and had haemolytic anaemia. The probable mechanism of the toxic effect of phenacetin on the haemopoietic system through induction of intravascular haemolysis (so called stibophen-type haemolysis) is discussed. One year follow-up demonstrated the reversibility of these haematological changes. PMID- 1295240 TI - [Ultrasonographic image of small-intestinal lymphoma]. AB - A case of small intestine malignant lymphoma was observed in a man aged 56 years. The only imaging method which demonstrated the presence of abdominal tumour was ultrasonography. The features of the USG image are discussed for facilitating the diagnosis of this rare tumour. PMID- 1295241 TI - [Subcutaneous emphysema of the anterior chest wall as the only symptom of spontaneous rupture of the esophagus]. AB - A diagnostically difficult case of Boerhaave's syndrome is reported. The patient gave a history of subcutaneous emphysema of the anterior chest wall as the only sign. Aspiration drainage through thoracotomy opening and artificial alimentation through jejunostomy were used with success. PMID- 1295242 TI - [A rare case of coexistence of aneurysm of the abdominal aorta and sigmoid neoplasm]. AB - A rare case is reported of coexistence of aortic abdominal aneurysm with sigmoid tumour. Emergency surgical treatment was instituted. PMID- 1295243 TI - [3-year observation of a child with fetal alcohol syndrome]. PMID- 1295245 TI - [Clinical course of symptomatic toxocariasis in a 10-year-old boy]. AB - A case is described of symptomatic toxocariasis in a boy, with massive invasion of the parasites and strong response of the organism. The course of the disease was very serious. PMID- 1295244 TI - [TAR syndrome (congenital thrombocytopenia and aplasia of the radial bones) in a 5-months-old boy]. AB - A boy aged 5 months had the TAR syndrome (thrombocytopenia and aplasia of radial bones) of autosomal recessive inheritance. Bilateral reduction of the length of the upper extremities included both forearm bones and humerus, so that the shoulder girdle was connected directly to the hand, with all fingers and thumb normally shaped. These skeletal anomalies were associated with thrombocytopenia. Various other abnormalities were present, with the most controversial anomaly being bilateral cleft of the lip and secondary palate. It may be an accidental coexistence of abnormalities or may suggest a common mechanism of the development of the TAR syndrome, Roberts syndrome and SC-phocomelia belonging to hereditary reduction of the extremities with identical mode of inheritance. PMID- 1295246 TI - [Therapeutic monitoring of drugs as a real progress in drug therapy]. PMID- 1295247 TI - [Mechanical obstruction of the small intestine]. AB - A group of 193 patients treated for mechanical occlusion of the small intestine in the years 1978-1987 at the hospital in Jaslo were analysed. The epidemiological index of this occlusion was 14.8 per 100 thousand of the population annually, the total mortality was 11.4%. The risk was greatest in patients with incarcerated hernia operated on with delay, especially in old age, in whom intestinal resection had to be done. In cases with necessary intestinal resection in the vicinity of the ileocaecal valve the results were better if the valve was resected with adjacent part of the intestine and ileostomy and colostomy was done. PMID- 1295248 TI - [Biochemical markers of bone remodelling and their usefulness in the diagnosis of osteoporosis]. AB - In 65 subjects (42 women and 23 men) aged from 40 to 80 years, at risk for primary or secondary osteoporosis development without concomitant diseases affecting renal and hepatic function and vitamin D metabolism, alkaline phosphatase activity (F.A.s) and total calcium level (Cas) were determined in the blood serum, and also the excretion in the morning urine portion of hydroxyproline and calcium was measured in relation to creatinine excretion (FUHpr/kr; FUCa/kr). In each patient an X-ray was done of the thoracolumbar spine, and on its basis the X-ray vertebral index was calculated. The study has been undertaken in order to elucidate whether the above stated compounds regarded as biochemical markers of bone remodelling, and the X-ray vertebral index are useful in the diagnosis of osteoporosis. An increased F.A.s activity in the blood serum, and higher values of the X-ray vertebral index were found both in the group of patients with primary and secondary osteoporosis, in relation to normal values. It was found that FUHpr/kr and FUCa/kr were increased in patients with secondary osteoporosis in comparison to patients with primary osteoporosis. A statistically significant correlation was also noted between FUHpr/kr and FUCa/kr, and F.A.s in patients with primary and secondary osteoporosis. In both studied groups no relationship was found between the value of the X-ray vertebral index, and the levels of biochemical markers of bone remodelling. PMID- 1295249 TI - [Evaluation of the effectiveness of medical prophylactic procedures applied to workers in ports]. AB - The purpose of the study is an evaluation of the effectiveness of the introduced medical prophylactic procedures among workers employed in zone of pollution with inorganic dusts. Medical and laryngological examinations were done several times in 125 workers of the Maritime Merchant Haven in Gdansk overloading phosphates, apatites, and crystalline sulphur compounds. In all studied patients systematic procedures were applied of rinsing the nasal and oral cavities with normal saline. A protective gel and also mucolytic drugs, among others Mistabron, were applied intranasally. Toxicological examinations were done of the nasal cavity washings with measurement of the quantity of phosphorus in cm3 before and after rinsing. The phosphorus concentration before the hydrotherapy procedure was X = 12.7 Ug/cm3, and X = 0.65 Ug/cm3 after the procedure. After using of prophylactic measures for two years, a reduction was achieved of the number of workers with respiratory tract diseases by 60% in the Sulphur Overloading Division, and by 34.2% in the Raw Phosphate Fertilizers Overloading Division. PMID- 1295250 TI - [Factors of the "acute phase" in proliferative diseases of the hemopoietic system]. AB - In proliferative diseases of the homeopathic system before starting and at the end of treatment, the values of 8 acute phase factors were studied simultaneously, that is: seromucoid, sialic acid, alpha 1 acid glycoprotein, alpha 1 antitrypsin, haptoglobin, ceruloplasmin, transferrin, and fibrinogen. In chronic myeloid and lymphatic leukaemia no constant increase nor decrease of the concentration of any of the factors was found. In non-Hodgkin lymphoma the concentration of one factor -ceruloplasmin was constantly increased, and that of two factors--sialic acid and fibrinogen was decreased, while in plasmocytoma the concentration of two factors--haptoglobin and ceruloplasmin was constantly increased. At the end of treatment the concentration of certain factors was changing. In chronic myeloid leukaemia the concentration of ceruloplasmin, fibrinogen, and seromucoid was decreasing, while in non-Hodgkin lymphoma the concentration of haptoglobin and fibrinogen was increasing, in chronic lymphatic leukaemia the concentration of haptoglobin and increasing, in chronic lymphatic leukaemia the concentration of haptoglobin and transferrin was increasing, and in plasmocytoma the concentration was increasing of haptoglobin, sialic acid, and transferrin. The result of treatment in chronic myeloid leukaemia was good, in non-Hodgkin lymphoma and chronic lymphatic leukaemia--moderate, and in plasmocytoma it was least beneficial. PMID- 1295251 TI - [Thoracic sympathectomy in the treatment of chronic ischemia of upper extremities and excessive sweating of the palms]. AB - The results are presented of treatment of 65 patients with chronic peripheral ischaemia of upper extremities and excessive sweating of the palms, in whom 78 thoracic sympathectomies were done by the Smitwick method in the years 1972-1989. The cause of ischaemia in 45 patients were organic changes (TO, AO), in 18 cases- functional changes (Raynaud syndrome), and in two patients--excessive sweating of the palms. Patients with trophic changes were 72% of those surgically treated. Long-term follow-up (8.5 years on the average) demonstrated a significant improvement in the group of organic changes in 84% of the surgically treated cases, in the group of functional changes in 83.2% of cases, and in excessive sweating of the palms in 100% of cases. In five patients contralateral effect of thoracic sympathectomy was observed. The authors discussed the extent of sympathetic trunk removal. They think that thoracic sympathectomy is a procedure of choice in cases of peripheral ischaemic changes in upper extremities not responding to conservative treatment. PMID- 1295252 TI - [Appearance of antibodies against hepatitis type A virus (HAV) in alcoholics]. AB - In 144 alcoholics--patients of alcoholic outpatient clinic anti-HAV antibodies were studied using the commercially available ELISA test. Anti-HCV antibodies were found in 86% of the alcoholics, and this prevalence was not higher than in the control group. No differences were found in the titre of antibodies against cytomegaly and herpes virus between the subjects with and without anti-HAV antibodies which suggests the specificity f the determined anti-HAV antibodies. PMID- 1295253 TI - [Chronic active hepatitis in alcohol abusers]. AB - 12 cases of chronic active hepatitis in chronic alcohol abusers are described. All patients were HBsAg negative and 7 were anti-HCV positive. Four out of 5 anti HCV patients quickly progressed to liver decompensation. It seems that chronic hepatitis seen in chronic alcohol abusers can be divided into two groups: one due to HCV infection and the other due to sensitivity to alcohol, respectively. PMID- 1295254 TI - [Cell-mediated and humoral immunity in children with down syndrome]. AB - Forty-three children were studied, aged 3 months to 10 years, with Down syndrome confirmed by karyotype studies. A statistically significantly decreased percent was found in them of "E" rosette-forming T lymphocytes. The percent of "EAC" rosette-forming B lymphocytes was normal. The concentration of IgG, IgA, and IgM immunoglobulins was about normal for age. PMID- 1295255 TI - [Concentration of serum proteins in children with down syndrome]. AB - In the serum of 41 children with trisomy 21 (Down syndrome) the concentration was determined of 10 proteins by the radial immunodiffusion method. It was found that the concentration of prealbumin and alpha 2-macroglobulin was lower than in healthy children. The concentration of acid alpha 1-glycoprotein, alpha 1 antitrypsin, haptoglobin, C4 complement component, and hemopexin was higher than in healthy children. The concentration of ceruloplasmin, C3 complement component, and transferrin was similar as in healthy children. PMID- 1295256 TI - [Familiarity with diseases of the esophagus, stomach and pancreas among trainees who applied for specialization in general surgery]. AB - The range of knowledge of the diseases of oesophagus, stomach and pancreas amongst 277 trainees in general surgery has been investigated by means of the 180 multiple-choice question examination. Analysis of the results revealed that the knowledge of the above subject with constituted 19% of the questions, does not differ from that of the rest of general surgery problems, distributed in the remaining 81% of the test's content. PMID- 1295257 TI - [Effect of oestro-feminal on lipid metabolism in postmenopausal women]. AB - The cessation of hormonal function of ovaries after menopause leads, among others, to changes of concentration of serum lipids and lipoproteins which may cause an increased risk for atherosclerosis. The purpose of the study was an evaluation of the effect of three- and six-month use of conjugated oestrogens on lipid metabolism in women after surgically induced menopause. Both after three and six months of treatment a reduction of intensity or abolition was found of the climacteric syndrome symptoms. After six months of substitutive therapy beneficial changes were observed in lipid metabolism (decrease of total and LDL cholesterol levels, and increase of HDL-cholesterol level). Hormonal therapy may play a protective role and prevent the development of atherosclerosis in women after menopause. PMID- 1295258 TI - [Evaluation of remote results in 80 intra-articular calcaneal fractures treated by various methods]. AB - The studies were done in 69 patients in whom 80 intra-articular calcaneus fractures were diagnosed of tongue or crush type. In the analysis of the remote results a subjective three-grade evaluation of the results was used as reported by the patients. The good results in 60% were closely related to the reconstruction of the shape of the calcaneus and its articular surface with simultaneous restoration of functional fitness of the foot. It was found that the fractures of tongue type were to be reduced by the Westhues method, while the crush fractures were to be treated surgically or functionally. Poor results were observed in all fractures not reduced and not immobilised additionally in plaster casts. PMID- 1295259 TI - [Myocardial infarction transmural and non-transmural]. PMID- 1295260 TI - [The heart in arterial hypertension]. AB - The data is presented on the pathogenesis of myocardial changes in arterial hypertension. The non-haemodynamic causes are discussed of myocardial hypertrophy, as well as the participation of collagen in its early phase and the haemodynamic consequences of hypertrophy and its regression. Hypotensive drugs and their ability ot prevent myocardial hypertrophy and (or) inducing of its regression were compared. PMID- 1295261 TI - [Epidermal growth factor and the digestive system]. PMID- 1295262 TI - [Sex hormone-binding globulin (SHBG) under physiological and pathological conditions]. AB - The concentration of sex hormone-binding globulin (SHBG) in blood depends on the sex, age, metabolic status of the organism, liver function, and gonad function. The circadian rhythm of somatotropin secretion is an important regulator of SHBG synthesis and secretion, and its passage from vascular bed to the tissues depends on somatomedin-C. The concentration of SHBG in the serum is thus the resultant of the synthesis of this glycoprotein in the liver and the ability of its uptake in the cells of target tissues for sex hormones. PMID- 1295263 TI - [A case of endocardial elastosis in a 5-week old infant]. AB - A case is presented of fulminant endocardial elastosis in a 5-week-old infant. The baby died after four days from the appearance of the first pathological symptoms with evidence of extreme circulatory insufficiency. Of main importance for intravital diagnosis was echocardiographic examination. The autopsy confirmed the diagnosis. The myocardium was hypertrophic without evidence of inflammation. The typical changes for this disease were found in parietal endocardium of both ventricles, both atria, as well as both atrioventricular valves, and aortic valve. PMID- 1295264 TI - [Two stage endoscopic-laparoscopic operation for calculi of the gall bladder and bile ducts complicated by acute pancreatitis]. PMID- 1295265 TI - The effects of aerobic exercise on psychological adjustment: a randomized study of sedentary obese women attempting weight loss. AB - This study evaluated the psychological effects of aerobic conditioning in 40 moderately obese, sedentary women participating in a 12-week behavioral weight loss program. Participants were randomly assigned to a no-exercise or moderate walking condition. Emotional impact of the treatment was assessed in two ways: (1) Subjects reported subjective mood prior to each eating episode and (2) the SCL-90-R was administered before and after the program. Exercisers lost more weight and body fat than non-exercisers. Both groups of subjects showed numerous improvements in mood as a result of participating in the weight loss program. Exercise had no specific differential effect on emotions as measured by daily mood ratings or the SCL-90-R. Exercise did not appear to add appreciably to the psychological benefits of losing weight in this sedentary obese population. Future studies utilizing longer periods of aerobic exercise training, larger sample size, and exercise specific measures are recommended. PMID- 1295266 TI - Women's social roles and their exercise participation. AB - How women's social roles such as parenthood, marital status and employment status affect their exercise participation, is important for the rational planning of suitable and effective exercise programs for women in different social contexts. A secondary analysis of a large data-base of urban women aged 20-49 (n = 5939) was carried out to determine if social roles, their characteristics and their combinations were related to women's exercise participation. Parenthood and marital status were significantly related to whether women exercise, and among those exercising, all three roles were significantly related to the amount of exercise. Statistical modelling, including all three roles and their interactions, controlling for age and education, showed that with respect to whether women exercise, parenthood affected exercise participation most and that its effect was dependent on age. Of the role characteristics only the number of children and overall satisfaction with daily activities improved the prediction of exercising. With respect to how much women exercise, the effect of parenthood interacted with marital status. Married parents were least likely to exercise very much. Of the role characteristics only overall satisfaction with daily activities improved the prediction of the amount of exercise. PMID- 1295267 TI - Diet and activity patterns of male and female co-workers: should worksite health promotion programs assume homogeneity? AB - Worksite health promotion programs address the health education needs of the average employee. Anthropometric measurements and 24h diet and activity diaries collected from co-workers reveal that lifestyle and subsequently, health education needs of men and women working for the same employer, in the same environment and performing similar tasks, may be different. In this study, males were marginally overweight and obese; females were within recommended limits. Although job related workloads were comparable, females were more active (24hEE/FFM) outside the work place. Females spent more time engaged in moderate weight-bearing domestic activities than did males. These results question the effectiveness of worksite health promotion program which ignore the different health education needs of male and female employees. PMID- 1295268 TI - Drinking behaviors of women in four occupational groups. AB - Questions about alcohol consumption, social and work contexts, and negative consequences related to alcohol use were asked of forty-nine academics, 27 physicians, 15 attorneys, and 169 business women. The majority of the women were light drinkers and their drinking does not appear to be accompanied by negative consequences. The exception to this is driving while intoxicated or riding with an intoxicated driver, behaviors which may be increasing as a result of business related or after work drinking. The women reported being in drinking settings relatively often. Frequency in drinking settings was correlated with both level of alcohol consumption and number of negative consequences of alcohol use. Presence in such settings may be related to women's employment status, and thus could be considered both a work-related risk factor and a location for abuse prevention activities. PMID- 1295269 TI - Gender and race: an interaction affecting the replicability of well-being across groups. AB - The Life Satisfaction Index (LSI) continues to be one of the most frequently used measures of well-being in social gerontology. Discrepancies in the operational use of the LSI, however, have made comparisons across studies difficult. Few studies have incorporated examination of the effect of gender/race interactions on the performance of the LSI. The purpose of this study was to examine differences in the hierarchical factor structure of life satisfaction among four gender/race groups using previously reported item pools and coding schemes. Three second-order, three-factor life satisfaction models were examined using confirmatory factor analysis techniques with four groups of older adults: White men (n = 846), White women (n = 1341), Black men (n = 177), and Black women (n = 287). In general, results showed differences in LSI factor structure across gender/race groups. With regard to coding scheme, models using Neugarten et al.'s original coding scheme (1961) and those using Wood et al.'s alternative scoring (1969) were similar. Examination of models using different LSI item pools showed that the factor structure of life satisfaction was affected by the gender/race interaction, underscoring the problem of misspecification resulting from the sum of LSI items and use of the summated score as a unidimensional measure of well being. Implications for future research are discussed. PMID- 1295270 TI - [A study of perspective vision]. AB - The present study describes the structure of monocular depth perception using an experimental basis. It regards the traditional theory of perspective, which is a subset of descriptive geometry, only as a construction guide for flat, albeit depth eliciting, visual stimuli. The investigation starts with a definition of structure as a set with an automorphism on it. In the present context the projection of the physical stimuli onto the retina provide a suitable ground set. After suitable confinement of the stimuli to a horizontal plane, the effects of eye and head movements of the subject can be represented as projective mappings of the retinal image onto itself. The present approach represents these as visual automorphisms. They are each characterized by a special visual invariance. The automorphisms form a group which comprises the affine, the affine unimodular and the orthogonal groups (in this order) as subgroups. Experimental studies of the different invariants of these subgroups as well as the consideration of other empirical observations lead to the conclusion that the structure of monocular space perception is characterized by the affine unimodular subgroup of the projective group. There are indications that the phenomena of size constancy can be represented by affine unimodular maps instead of orthogonal (metric) maps as sometimes has been conjectured. PMID- 1295271 TI - [Experimental induction of emotional conditions--alternatives to the Velten method]. AB - The technique most often used to induce emotion is based on self-referent statements read by the subjects (Velten, 1968). This technique is known to be of intermediate efficiency. Therefore film and hypnosis-like procedures were investigated as alternative techniques. Efficiency was tested using two selected scales of a mood questionnaire (SES by Hampel, 1977). The subjects were male and female students. Both alternative procedures allowed us to induce significant changes in Ss' moods. The film method was more efficient than the Velten technique in inducing a negative mood, whereas it was equally efficient in inducing a positive mood. The hypnosis-like procedure, however, was not more efficient than the Velten-technique. Obviously film is a quite efficient and easy applicable alternative technique to induce moods. PMID- 1295272 TI - [Dependence of 'audio-phonatoric coupling' of speech rate and speech loudness]. AB - The 'audio-phonatoric coupling' (APC) was investigated in two independent experiments. Slightly delayed auditory feedback (delay time 40 ms) of the subjects' own speech was used as experimental method. The first experiment was conducted to examine whether the strength of the APC depends on the speech rate. In this experiment 16 male Subjects (Ss) were required to utter the testword/tatatas/either with stress placing on the first or second syllable at two different speech rates (fast and slow). In 16% of the randomly chosen speech trials, the delayed auditory feedback (DAF; 40 ms delay) was introduced. It could be shown that the stressed phonation was significantly lengthened under the DAF condition. This lengthening was greater when Ss spoke slowly. The unstressed phonations were not influenced by the DAF condition. The second experiment was conducted to examine whether or not speech intensity effects APC. Nine male Ss were required to utter the testword/tatatas/either with stress placing on the first or second syllable using three different speech intensities (30 dB, 50 dB and 70 dB). In 16% of the randomly chosen speech trials DAF condition was introduced. It could be shown that speech intensity does not influence the DAF effect (lengthening of stressed phonation). These findings were taken as evidence that the auditory feedback of the subjects' own speech can be incorporated into speech control during ongoing speech. Obviously, this feedback information is efficient only during the production of stressed syllables, and varies as a function of speech rate. In addition, the significance of stressed syllables for the structuring of speech is discussed. PMID- 1295273 TI - [Judgment of the credibility of rape allegations: a content analytic field experiment]. AB - This study explores the issue of whether allegations of rape can be correctly identified as true or false on the basis of a set of content criteria used successfully in previous studies with respect to children's accounts of sexual abuse. A sample of 30 authentic protocols of police interrogations of women reporting rape were selected for the study. Fifteen cases were classified as false accounts because the complaints eventually confessed to having fabricated their allegations. The remaining cases were classified as true rapes on the basis of medical and other corroborating evidence. A group of experienced police officers (N = 30) judged these cases in terms of their credibility on the basis of the 19 content criteria suggested by Steller & Kohnken (1989) and gave an overall judgment of the true vs. false nature of each statement. A second group of police officers (N = 22) judged the credibility of the statements without reference to these criteria. The findings from a series of discriminant function analyses showed that the set of criteria as a whole is successful in distinguishing between true and false rape allegations. The results of the stepwise discriminant function analyses reveal which criteria in particular contribute to the correct identification of true and false cases. However, the higher percentage of correct classifications in the group using the content criteria was only marginally significant compared to the second group judging the cases without reference to the criteria. Altogether, the findings of this study support the basic tenet of statement analysis that the linguistic features of a statement contain essential clues for assessing its credibility. PMID- 1295274 TI - [Reaction time and temporal serial judgment: corroboration or dissociation?]. AB - Dissociations between a motor response and the subject's verbal report have been reported from various experiments that investigated special experimental effects (e.g., metacontrast or induced motion). To examine whether similar dissociations can also be observed under standard experimental conditions, we compared reaction times (RT) and temporal order judgments (TOJ) to visual and auditory stimuli of three intensity levels. Data were collected from six subjects, each of which served for nine sessions. The results showed a strong, highly significant modality dissociation: While RTs to auditory stimuli were shorter than RTs to visual stimuli, the TOJ data indicated longer processing times for auditory than for visual stimuli. This pattern was found over the whole range of intensities investigated. Light intensity had similar effects on RT and TOJ, while there was a marginally significant tendency of tone intensity to affect RT more strongly than TOJ. It is concluded that modality dissociation is an example of "direct parameter specification", where the pathway from stimulus to response in the simple RT experiment is (at least partially) separate from the pathway that leads to a conscious, reportable representation. Two variants of this notion and alternatives to it are discussed. PMID- 1295275 TI - [Evaluation algorithm for eye movement patterns during a problem solving task]. AB - Cognitive processes are accompanied by eye movements, which are interrupted by fixations of an almost infinite number of points in the visual field. To investigate these processes, a systematic analysis of those movements is required to structure the long sequences of fixations. This task is possible if there are interrelationships between the ongoing thought processes and the fixations. Such interrelationships may manifest themselves through certain patterns of eye movements. It often happens that subsets of visual points are being looked at repeatedly. This is because a cognitive connection among the subset's elements is being discovered or created by such repetition. The method presented here attempts to achieve automatic recognition of fixation point patterns. Its usefulness is demonstrated using data from an experiment where eye movements were recorded while subjects were solving Raven Test items. The method may be characterized as a variant of time series analysis for nominal data. It is suitable for non-numerical data in general. PMID- 1295276 TI - [The tail suspension test: its theory and practical application]. AB - The tail suspension test (TST) was originally proposed by Steru et al (1985) as a primary screening test of anti-depressant drugs. In this test, it is shown that tail suspension-induced immobility of mice is specifically antagonized by such drugs. More recently, the automated version of TST (ITEMATIC-TST) was developed by the same authors. In the present paper, we described our own device which utilized spring, contactless micro angle potentiometer, A/D converter and personal computer. Results obtained with this apparatus showed that repeated, not single, administration of tricyclic and atypical antidepressants could reverse the immobility of mice. Methamphetamine also activated the behavior, but other psychotropic drugs did not have positive results. Based on these findings, the usefulness and problems of our device were discussed as compared with the original TST. PMID- 1295277 TI - [Anxiety and brain noradrenaline system]. PMID- 1295278 TI - Correction of the luteal phase defect with clomiphene citrate. AB - Among the various strategies proposed for the therapy of the luteal phase defects (L.P.D.), the administration of clomiphene citrate during the early follicular phase has proved to be very effective even though it is not one of the most used. Nevertheless, very soon has been risen the question if such drug acts by an overphysiological increase of the hormonal levels or instead by a re-balance of the altered latter ones. In order to answer this question a clinical study was carried out during 265 cycles on 63 normally ovulating and menstruating women, whose 27 with a luteal phase defect (L.P.D.), detected by clinical, echographic, endocrine, and morphological criteria. Each of these latter patients were given clomiphene citrate, 100 mg per day from the 2nd to the 6th day of the cycle, for a total of 108 cycles. The other 36 women without any luteal abnormality, were used during 156 cycles, as a control group. At the end of our study there were no significant differences in all parameters between two studied groups. This suggest that early follicular phase administration of clomiphene citrate in these pathologies can act by gradually improving the luteal function. PMID- 1295279 TI - Gynecologic interventional radiology. AB - Interventional radiology now finds a wide range of applications in the gynecologic area. They can be divided in general procedures applied to gynecology and procedures specific to gynecology. PMID- 1295280 TI - CA-125 and ovarian hyperstimulation. AB - The ovarian hyperstimulation syndrome (OHSS) has become more and more frequent in relation to the spread of the method of superovulation by means of pharmacologic induction and consequently the necessity of measures suitable for preventing and controlling it has been more and more improved. Among them the discovery of indicators which could reveal as early and sensitive as possible the onset and, when it is possible, also the degree of severity of this syndrome, holds an important position. Till now only the serum estradiol concentration performed this task, among the other things, in an incomplete and not-well defined manner, but its inadequacy has stimulated once again the search for new substances which would allow attention to be drawn to the development, entity and evolution of this syndrome in compliance with necessary requisites with greater timeliness, and tenacity. Therefore the behaviour of the serum CA-125 levels has been evaluated for the first time in 31 cycles of 31 patients, which were stimulated by gonadotropins (FSH, FSH/LH, HCG), of which 21 underwent ovarian hyperstimulation of various degree (10 of I, 8 of II and 3 of III grade), while the other 10 had no complications. The blood levels of this marker rose above the limit considered physiological (35 UI/ml) during the luteal phase in all the stimulated cycles and, in hyperstimulated ones always exceeded 70 UI/ml; in addition the serum CA-125 levels correlated very well with ovarian dimensions, degree of severity of the syndrome and estrogenic concentrations during only luteal phase, in the hyperstimulated cycles and continued to remain high or even increased in case of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295281 TI - Indomethacin and fertility in experimental endometriosis. AB - Clinical and experimental evidence showed an increased concentration of prostaglandins in peritoneal fluid in cases of endometriosis. The aim of this study was to verify whether an antiprostaglandin drug can restore fertility in cases of endometriosis. For this reason endometriosis was induced in 4 groups of 10 rats. Group A was treated with indomethacin both in the pre-ovulatory and in the post-ovulatory phase. Group B was treated in the pre-ovulatory phase. Group C was treated in the post-ovulatory phase. Group D was not treated. Ten other rats (group E) underwent a sham operation and were used as a control. Twelve days after mating, gestational sacs and corpora lutea were counted and the nidation index was calculated. Only indomethacin administered during the pre-ovulatory phase completely restored fertility in these rats. PMID- 1295282 TI - Effect of human gamma interferon on mice testis: a quantitative analysis of the spermatogenic cells. AB - Effect of Human Gamma Interferon (Hu-IFN-gamma) on the testicular histology was studied in mice. Male mice were administered Hu-IFN-gamma intratesticularly at the doses of 2, 10 and 20 micrograms/testis in a volume of 1.0 microliter isotonic normal saline. Contralateral testis served as control and was administered same amount of vehicle. All the animals were sacrificed 7 days after drug administration. Body weight and the weights of testis and epididymis were not affected by IFN treatment nor was there any effect of the drug on the motility of the vas deferens spermatozoa. Low dose of IFN (2 micrograms) did not have significant effect on the histoarchitecture of the testis and various spermatogenic elements, a progressive damage was however observed with the increasing doses of IFN. Pronounced deleterious effect of IFN on the testis leading to desquamation of the germinal epithelium, reduction in the germinal cell height and tubular diameter was observed with 20 micrograms dose. Quantitative studies on seminiferous epithelium showed a significant decrease in the number of Sertoli cells, stage-7 spermatids and stage-16 spermatozoa. The ratios of resting type spermatocyte: type A spermatogonia and stage-7 spermatids: pachytene spermatocyte was also reduced. The ratios of pachytene spermatocyte: resting spermatocyte and stage-16 spermatozoa: stage-7 spermatids were however not affected by IFN treatment. In another experiment IFN was administered (2 micrograms/day) subcutaneously to male mice for 30 days. No effect of drug treatment on body weight, organ weight, sperm motility and histology (including morphometry) of the testis was observed. Our data suggest that IFN action at testis may be associated with the antiproliferative effect of interferon. PMID- 1295283 TI - [Experimental pancreas transplantation]. AB - Experimental pancreatic transplantation was performed in dogs using different surgical techniques. Ten dogs underwent whole organ graft with diversion of exocrine secretion by anastomosis of duodenal segment to bladder (six animals) and of duodenum to a jejunal loop (four animals). Segmental pancreatic grafts were performed in 10 dogs with ductal filling with polymer in six animals and duct ligation in four dogs. It is concluded that segmental pancreatic graft with ductal filling with polymer is preferable to the other surgical techniques. PMID- 1295284 TI - [Incidence of cholelithiasis in patients with cancer of the colon and adenomatous polyp]. AB - Recent international publications remark the association about carcinoma of the colon and cholelithiasis. These two entities with similar geographical distribution can be seen frequently in the modern western societies, being the cause as aetiological factors the low content in dietetics fiber. Different studies about the carcinoma of the colon and cholelithiasis pathogenesis had lead the possibility that the abnormal degradation of bile acids for the colonic bacterias, could be responsible of each one of these illness. The exposition of colonic mucosa to products of degradation of bile acids, specially secondary bile acids, may play a role in the etiopathogenic of colon carcinoma. It was analysed 135 patients with colon carcinoma or adenomatosis polyps, 42 with cholelithiasis or cholecystectomized for the same cause (31.1%), although in the control group, only 2(5%) had cholelithiasis. The female predominated the group of colon carcinoma and cholelithiasis, as well as cholecystectomized for that cause. The most frequent associated pathology was the diverticulosis. PMID- 1295285 TI - [Professional risk: hepatitis B. Vaccination strategies in a general hospital]. AB - The risk of contracting hepatitis B: (HBV) by health workers is widely accepted. In 1989 our Hepatology Service started a voluntary anti-HBV vaccination program, employing recombinant vaccine (SKF) by intramuscular route with a 0-1-6 month schedule after screening with antibody against the anti-core HBV antigen (AntiHBc Elisa Abbott). Initially, it was planned to monitor antibody titers against superficial antigen (Anti-HBs) 30 days after the last dose. An epidemiological form listing personal data, working area, profession, seniority, written consent for blood extraction and tentative acceptance of vaccination, was completed by 357 hospital staff members. After serological screening, only 184 (51%) workers agreed to receive vaccination. Given the paucity of volunteers, an attempt was made to explain this degree of reluctance by a randomized blind voluntary survey, to which 349 hospital staff members and 40 medical students replied. Questions were related to knowledge concerning vaccination in general, hepatitis and particularly hepatitis B, and specific anti-HBV vaccination. An appraisal of data gathered disclosed a considerable lack of information not only on the risk of HBV infection and its complications, but also on the existence of a suitable vaccine. Non-existent adverse effects of vaccination were mentioned, including AIDS (Acquired Immuno-Deficiency Syndrome), hepatitis and cirrhosis, among others. To overcome this obstacle, we held a two-day workshop on hepatitis B prevention and prophylaxis intended for medical and ancillary staff. After the meeting, which were attended by 221 members, 48 individuals, comprising 25 physicians and 23 nurses, spontaneously requested to be vaccinated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295287 TI - [Intestinal duplication. Report of 2 cases]. AB - Intestinal duplications are rare and they result from embryological failures in the canalization of the gastrointestinal tract. This paper presents a case of ileal intestinal duplication and its differential diagnosis from Meckel's diverticulum. Besides, a case of rectal duplication in an asymptomatic elder patient is presented. PMID- 1295286 TI - [Manometric effects of pinaverium bromide in irritable bowel syndrome]. AB - The effects of pinaverium bromide on colonic motility were investigated in a controlled, controlled, cross-over study in 32 patients with irritable bowel syndrome. Constipation was clearly predominant in one group of 16 patients, and diarrhea in the other group of 16. Manometric measurements were taken of the colonic motor response generated by distention of a balloon inserted to the rectosigmoid junction. Measurements were taken before and one hour after ingestion of two tablets containing placebo or two tablets each containing 50 mg of pinaverium bromide. Following intake of placebo the motility index increased from the basal value in patients with constipation, and resistance to distention decreased in the diarrhea group. These changes were attributable to repetition of the mechanical stimulus within a relatively brief time lapse, or more probably to the ingestion of liquid which accompanied intake of tablets. Compared with placebo, pinaverium bromide induced inhibition of both effects. From the therapeutic point of view, the decrease in motility index seen in patients with irritable bowel syndrome and constipation is particularly interesting. PMID- 1295288 TI - [Benzodiazepine metabolism in experimental extrahepatic cholestasis]. AB - The aim of the present study was to determine the effect of bile flow impairment on hepatic lorazepam detoxication and its relationship with the liver microsomal membrane phospholipid composition. It was observed a decrease of phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and sphingomyelin content and an increase of phosphatidylserine and phosphatidylglycerol. A similar activity on lorazepam detoxication was observed when cholestatic rats were compared to controls. These results suggest that there is a different modulation than the phospholipid environment play the key role in lorazepam metabolism, independently of membrane. PMID- 1295290 TI - [Diagnostic value of abdominal pain in intra-abdominal desmoid tumor]. AB - Desmoid tumors are rare, less than 0.1% of all tumors (6.2%). The word desmoid has been recognized since 1838, and applied to non-encapsulated tumors, of connective origin and locally infiltrative. Generally, their course is painless and the recurrence rate is high if resection has not been complete. Most of these tumors can be found in different anatomic areas, most commonly the anterior abdominal wall although other sites, intra- or extra-abdominal, have been reported. We describe the case of a 50 year old female patient, with abdominal pain caused by an intraabdominal desmoid tumor. PMID- 1295291 TI - [Helicobacter pylori, gastritis, and peptic ulcer]. PMID- 1295289 TI - Gastroparesis: medical or surgical therapy? AB - It is presented the case of a 63-year-old female patient, who was admitted to the hospital for the first time, because of clinical picture compatible with acute cholecystitis and choledocholithiasis. She underwent cholecystectomy common bile duct (cbd) exploration, and duodenotomy, with the extraction of two stones located in the distal cbd. During her postoperative course, she had been under a great emotional tension, and ten days after her surgical intervention, she developed symptoms and signs of acute gastric dilatation, requiring a second admission. A barium meal and an upper endoscopy revealed gastric dilation, with marked pyloric spasm. Her complaints improved after conservative therapy was instituted. No surgical intervention was necessary. We concluded that the cause of her gastric retention was due to the emotional stress present during her postoperative course, which produced marked pyloric spasm, and not from an organic cause. PMID- 1295292 TI - [Chemical composition of gallstones in Santa Cruz--Bolivia]. AB - The knowledge of the gallstones chemical composition is very important from view point of lithogenesis and possible medical therapy of dissolution. The composition (chemical) of gallstones in 30 consecutive cholecystectomized patients were studied in the 2nd. Department of Surgery of Hospital San Juan de Dios, Santa Cruz, Bolivia (altitude 1900 m). All gallbladder stones were washed, counted, measured and dried before sending them to Japan to be processed. The composition of gallstones was analyzed by infrared absorption spectroscopy. Cholesterolemia, age, sex and number of stones were analyzed in cases of pure cholesterol stones. The incidence of pure cholesterol stones was 56.6%, statistically similar to be reported by other authors, but very low if compared with the valley area of Bolivia (Cochabamba altitude 2300 m) where hypothyroidism is frequent. Hypercholesterolemia had little relation with the pure cholesterol gallstones. There was no difference in the chemical composition and the size of the stones, but while their number was small, cholesterol stones were more frequent. The low incidence of pure cholesterol stones may show a bad nutritional condition of our population (poor fat and protein content) and this result is important in order in using the new advance: lithodissolvent drugs. PMID- 1295294 TI - Proceedings of the 4th International Meeting of the International Society for the Use of Resealed Erythrocytes as Carriers and Bioreactors. Urbino, Italy, September 5-7, 1991. PMID- 1295295 TI - Studies with biotinylated RBC: (1) use of flow cytometry to determine posttransfusion survival and (2) isolation using streptavidin conjugated magnetic beads. AB - Methods are reported for the quantitation and isolation of biotinylated red blood cells (B- RBC). The first method is for determination of posttransfusional survival of rabbit RBC by flow cytometry. The survival of B-RBC was measured using both fresh and paraformaldehyde-fixed cells with similar results. The posttransfusion survival of rabbit RBC measured in this way was normal. There was no indication of increased cell destruction due to antibodies directed against B RBC and no evidence for loss of biotin from circulating cells. The second methodology is for the isolation of B-RBC from blood with streptavidin-coated magnetic beads. At least eighty percent of positive cells were recovered with very few false positives. Both methods may be helpful in the study of resealed erythrocytes. PMID- 1295293 TI - On red blood cells, hemolysis and resealed ghosts. PMID- 1295296 TI - Resealing of protein tyrosine kinase substrates into human erythrocytes by rapid freezing and thawing in liquid nitrogen. PMID- 1295297 TI - The application of newer concepts of oxygen transport to the evaluation of the potential utility of reduced Hb-O2 affinity. PMID- 1295298 TI - Single cell analysis of factors increasing the survival of resealed erythrocytes in the circulation of mice. AB - Erythrocytes labeled with fluorescent membrane markers were reinfused into mice. Blood samples removed periodically were analyzed by flow cytometry for survival of labeled cells. Normal erythrocytes labeled with the markers persisted in the circulation for 45 days. A fraction of lysed and resealed erythrocytes labeled with marker were rapidly cleared from the circulation; the remainder were removed at approximately the same rate as normal cells in the same animal labeled with marker of another color. Lysis in a minimal volume of buffer and addition of ATP during lysis both increased the fraction of cells surviving initial clearance. PMID- 1295299 TI - Entrapment of purified alpha-hemoglobin chains in normal erythrocytes as a model for human beta thalassemia. AB - Entrapment of purified alpha-hemoglobin chains within normal erythrocytes resulted in structural and functional changes very similar to those observed in human beta thalassemic erythrocytes (Table 1). Membrane proteins and reactive thiol groups were decreased in a pattern similar to that observed in vivo in beta thalassemia. In addition, the alpha-chain loaded cells exhibited evidence of enhanced oxidant stress. Functionally, entrapment of alpha-chains resulted in the loss of cellular and membrane deformability, an important pathologic characteristic of the beta thalassemic erythrocytes. These results also demonstrate that the loss of membrane proteins and thiols as well as the functional loss of cellular and membrane deformability characteristic of the beta thalassemic cell occur very rapidly in the presence of soluble alpha-chains. Utilizing this model of the thalassemic erythrocyte, it is now possible to directly investigate the mechanisms underlying the cellular pathophysiology induced by excess alpha-chains. An understanding of these mechanisms may allow for the development of therapeutic interventions that would improve effective erythropoiesis and prolong erythrocyte survival in the peripheral circulation of individuals with beta thalassemia. Successful therapeutic interventions would diminish the frequency and/or necessity of blood transfusions and chelation therapy in beta thalassemia. PMID- 1295300 TI - ATP monitoring in human red blood cells with luciferase introduced intracellularly. PMID- 1295301 TI - Antagonism of the lethal effects of cyanide with resealed erythrocytes containing rhodanese and thiosulfate. AB - A new concept has been presented for the antagonism of cyanide and possibly other chemical toxicants. Until now, only a half dozen truly specific "antidotes" were known. There are many other "antidotes" which merely prevent the absorption or enhance the elimination of a toxic compound rather than specifically destroying the substance to prevent its toxic effect. This new approach has considerable conceptual significance in toxicology, as it suggests the encapsulating other enzymes to degrade various other chemical toxicants. There are many chemical toxicants for which there are no specific antidotes, and the conceptual approach of employing erythrocyte-encapsulated enzyme provides an innovative, specific approach to antagonize the toxic and lethal effects of these chemicals. PMID- 1295303 TI - Immunological response to L-asparaginase loaded into red blood cells. PMID- 1295302 TI - Acetaldehyde oxidation by aldehyde dehydrogenase loaded erythrocytes. PMID- 1295304 TI - Normalization of hyperglycemia in diabetic mice by enzyme-loaded erythrocytes. PMID- 1295305 TI - Comparison of uricase-bound and uricase-loaded erythrocytes as bioreactors for uric acid degradation. PMID- 1295307 TI - Xenobiotic detoxification by GSH-loaded erythrocytes. PMID- 1295306 TI - IHP entrapment into human erythrocytes: comparison between hypotonic dialysis and DMSO osmotic pulse. AB - Three different blood units were treated separately by the hypotonic dialysis (HD) and the dimethylsulphoxide osmotic pulse (DMSO) method, in order to load the erythrocytes with inositol hexaphosphate. A detailed comparison between the two loading techniques was performed by monitoring the red cell distribution patterns on discontinuous Percoll density gradients, the RBC oxygen affinity and the amount of the main intracellular organic phosphates with the 31P-NMR. The results obtained showed that: (1) The HD loading produces a redistribution of the RBC fractions with a concomitant smoothing of the relative differences among distinct fractions (2) only a minor portion of erythrocytes (from 8.5 to 24.9% of total RBCs) are loaded with IHP after the DMSO treatment. All of these cells move to the lightest fraction (d = 1.080 g/ml). (3) Both HD and DMSO IHP-loaded cells show an increase in P50 (basal vs. after loading, means +/- SD: 25.8 +/- 3.0 vs. 52.5 +/- 3.2 mm Hg) correlated to the IHP incorporation (mean intracellular IHP concentration: 4.2 mmol/l RBC). (4) probably the IHP incorporation efficiency could be probably improved at least by increasing the IHP concentration during the treatment. PMID- 1295308 TI - A new chemotherapeutic agent: L-asparaginase entrapped in red blood cells. PMID- 1295309 TI - Rubomycin loaded erythrocytes in the treatment of mouse tumor P388. PMID- 1295310 TI - Erythrocytes as carriers of new anti-opioid prodrugs: in vitro studies. AB - In using a reversed hypoosmotic lysis and resealing process, internalization of Naloxone or Naltrexone prodrugs as new opioid antagonists into red blood cells (RBC) can be obtained. We describe the entrapment method and haematological parameters of such RBC carriers. Percentages of internalization range between 35% and 70%, depending on the prodrug. The stability of the different prodrugs within RBC, after in vitro internalization have been compared at 4 degrees C and 37 degrees C. These studies were performed in order to screen and choose the most interesting prodrugs for in vivo studies. Some prodrugs tested appeared to be stable after 24 hours of incubation, but others were not. The intracellular ATP and 2,3 BPG concentrations of RBC carriers were similar to the control. PMID- 1295312 TI - Modulation of thiopurine metabolism in native human erythrocytes. PMID- 1295311 TI - Interactions of carboplatin with human erythrocytes and murine erythroleukemic cells. PMID- 1295313 TI - Red blood cells as advanced drug delivery systems for antiviral nucleoside analogues. PMID- 1295314 TI - Targeting of erythrocytes to cytotoxic T-cells. PMID- 1295315 TI - Introduction to in vivo targeting. PMID- 1295316 TI - In vitro targeting of doxorubicin loaded canine erythrocytes to cytotoxic T lymphocytes (CTLL). PMID- 1295317 TI - Pharmacokinetics of doxorubicin loaded and glutaraldehyde treated erythrocytes in healthy and lymphoma bearing dogs. PMID- 1295318 TI - Clinical evaluation of glutaraldehyde-treated canine erythrocytes in normal dogs. PMID- 1295319 TI - Sickle cells modified by an osmotic pulse in the presence of inositol hexaphosphate have decreased intracellular hemoglobin concentration and decreased in vitro sickling without prolonged in vivo survival. AB - An osmotic pulse was used to modify red blood cells (RBC) from two patients with sickle cell disease, resulting in an increased volume and decreased hemoglobin content. This treatment yielded cells which were divided into two populations, one in which RBC had markedly decreased hemoglobin concentration and another in which the cells appeared to be unmodified. Morphological sickling at low oxygen partial pressure was markedly decreased. However, there was no evidence for increased RBC lifespan when the 51Cr-labeled, modified cells were reinfused. PMID- 1295320 TI - A baboon model to test physiological and adverse effects of human red cells loaded with inositol hexaphosphate (IHP). PMID- 1295321 TI - Susceptibility of carrier erythrocytes to a natural hemolytic system. PMID- 1295322 TI - Gd-DOTA loaded into red blood cells, a new magnetic resonance imaging contrast agents for vascular system. PMID- 1295323 TI - Quantitative IHP determination by 31P-NMR: proposal for a standardized protocol. PMID- 1295324 TI - Determination of inositol hexaphosphate (IHP) in human IHP-loaded red blood cells by a simple high performance liquid chromatography method. PMID- 1295325 TI - Determination of purity of commercially available inositol hexaphosphate (phytates) and preparation of a reference material. PMID- 1295326 TI - Standardization of an encapsulation system: a method to remove fragile cells. PMID- 1295327 TI - The dialysis encapsulation process: the role of endocytosis. PMID- 1295328 TI - Properties of hypotonized, crosslinked and crosslinked- permeabilized rat erythrocytes as potential carrier systems. AB - The osmotic fragility curves of isotonic rat RBCs, studied at pH 8 to avoid the Hb insolubility, are similar to those in humans at pH 7.4. Hypotonized rat RBCs, either directly or dialysed (0-24 h), are more hemolysis-resistant than isotonic rat RBCs. The discocyte-stomatocyte-spherocyte transformation can be observed with scanning electron microscopy. Protein crosslinking with dimethyl suberimidate can stabilize RBCs. The crosslinking level (60%), the cellular yield (80%), the mechanical and hemolytic resistance and the protective effect of enzyme activities, were studied in crosslinked or crosslinked- permeabilized RBCs after digitonin treatment. The normal discocytic shape of RBCs under scanning electron microscopy becomes stomatocytic in crosslinked and crosslinked- permeabilized RBCs with an erosioned surface. PMID- 1295329 TI - Membrane properties of senescent and carrier human erythrocytes. PMID- 1295330 TI - The new biology and vaccine research. PMID- 1295331 TI - Induction of T helper cells and cytokines for mucosal IgA responses. AB - CD4+ Th cells and their derived cytokines play an important role in the regulation of IgA responses in the mucosal immune system. Th1 and Th2 cells induce different Ig isotype and IgG-subclass responses. Further, cytokines produced by Th2-type cells (e.g., IL-5 and IL-6) have been shown to induce PP sIgA+ B cells to secrete IgA. Our studies have now shown that oral immunization with SRBC selectively induces Th2-type cells in PP while systemic (I.P.) immunization with SRBC predominantly induces Th1-type cells. It is tempting to suggest that Th2 cells which produce IL-5 and IL-6 tend to be predominant in mucosal effector regions, such as the salivary glands and LP tissues and account for the predominant IgA responses which characterize these tissues. The PP contain B cell subsets which respond to IL-5 and IL-6, and these are largely restricted to the PNALo non-GC (memory) sIgA+ B cells. The importance of CD4+ Th cells in the regulation of IgA responses has also been shown by the depletion of CD4+ Th cells in anti-L3T4 (CD4)-treated mice. Loss of CD4+ Th cells from mucosal tissues resulted in dramatically decreased numbers of IgA plasma cells in the small intestine and led to a reduction in IgA SFC in isolated LP cells. The overall size of PP was reduced and the GCs were absent; however, the relative frequency of sIgA+ B cells in PP did not change, possibly suggesting that CD4+ Th cells do not influence switches to IgA. PMID- 1295332 TI - Cytokine production and T cell receptor expression by salivary gland T cells and intraepithelial T lymphocytes for the regulation of the IgA response. AB - The IgA effector sites such as the salivary glands and the intestinal tract contain several distinct T cell subsets which possess unique biologic characteristics. Freshly isolated CD3+ T cells from the salivary glands, the LP region of the small intestine and IELs all harbor T cells which spontaneously produce Th1 (IFN-gamma)- and Th2 (IL-5 and IL-6)-type cytokines. Interestingly, a high frequency of IL-5-producing Th2-type cells is always associated with the occurrence of increased numbers of IgA plasma cells (e.g., the salivary glands and the LP region of the small intestine). Further, the salivary gland CD3+ T cells can be divided into three distinct subsets including those of CD4+, CD8- (12-23%), CD4-, CD8+ (18-25%) and DN (6-16%) T cells. In terms of TCR expression, CD4+, CD8- and DN T cells exclusively expressed alpha/beta TCR and gamma/delta TCR, respectively. One of the unique features of the salivary gland T cells is that like IELs, relatively high numbers of gamma/delta TCR-bearing cells are seen in the CD4-, CD8+ T cell fraction. Since our study has provided important new evidence that these gamma/delta TCR-bearing T cells from IELs of mice orally immunized with TD antigen possess the capability of abrogating oral tolerance to antigen-specific immune responses including the IgA isotype, one can visualize that gamma/delta TCR+ T cells can be essential regulatory T cells which protect (or enhance) alpha/beta TCR+, CD4+ Th cells for maximum IgA responses at IgA effector tissues including the salivary glands, and the gastrointestinal tract in the presence of an active state of systemic unresponsiveness or oral tolerance. PMID- 1295333 TI - Prospects for human mucosal vaccines. AB - The selective induction of antibodies in external secretions and mucosal T cell mediated immunity are desirable for the prevention of various systemic as well as predominantly mucosa-restricted infections. An enormous surface area of mucosal membranes is protected primarily by antibodies that belong, in many species, to the IgA isotype. Such antibodies are produced locally by large numbers of IgA containing plasma cells distributed in subepithelial spaces of mucosal membranes and in the stroma of secretory glands. In humans and in some animal species, plasma-derived IgA antibodies do not enter external secretions in significant quantities and systemically administered preformed IgA antibodies would be of little use for passive immunization. Systemic administration of microbial antigens may boost an effective S-IgA immune response only in a situation whereby an immunized individual had previously encountered the same antigen by the mucosal route. Immunization routes that involve ingestion or possibly inhalation of antigens lead to the induction of not only local but also generalized immune responses, manifested by the parallel appearance of S-IgA antibodies to ingested or inhaled antigens in secretions of glands distant from the site of immunization. Convincing evidence is available that antigen-sensitized and IgA committed precursors of plasma cells and T cells from IgA inductive sites (e.g., BALT, GALT, and tonsils) are disseminated to the gut, other mucosa-associated tissues, and exocrine glands. However, due to the limited absorption of desired antigens from the gut lumen of orally immunized individuals, repeated large doses of antigens are required for an effective S-IgA response. Novel antigen delivery systems for the stimulation of such responses has been briefly reviewed here. These, of course, include genetically engineered bacteria and viruses, CT/CFB, liposomes and microspheres. Live attenuated or genetically manipulated bacteria expressing other microbial antigens have been used for selective colonization of GALT. Unique antigen packaging and the use of adjuvants suitable for oral administration hold promise for an efficient antigen delivery to critical tissues in the intestine and deserve extensive exploration. The oral immunization route appears to have many advantages over systemic immunization; however, one must consider alternate IgA inductive sites and compartmentalization within the Common Mucosal Immune System. In addition to providing immunity on mucosal surfaces, which are the most common sites of entry of infectious agents, the mucosal routes of administration are more acceptable and do not require stringent criteria applicable for injectable vaccines, storage problems may be simplified, and large populations of individuals can be immunized simultaneously without the assistance of highly trained health personnel. PMID- 1295334 TI - Immunological adjuvants. PMID- 1295335 TI - M cell-mediated antigen transport and monoclonal IgA antibodies for mucosal immune protection. PMID- 1295336 TI - A mechanism of passive immunization with monoclonal antibodies to a 185,000 M(r) streptococcal antigen. AB - The cell surface streptococcal antigen (SA) I/II of 185,000 M(r) is an immunodominant molecule that expresses one or more adhesion determinants. A series of 14 monoclonal antibodies (MAb) to defined parts of SA I/II were generated and some of these were used in passive immunization of macaques. Topical administration of selected MAb to the teeth of macaques prevented colonization of endogenous or implanted exogenous Streptococcus mutans for a period of 1 year. Significant reduction of both smooth surface and fissure caries was found in macaques who had MAb (Guy's 1) applied to their teeth, as compared with saline-treated animals. A series of in vivo passive immunization experiments was then carried out in 57 human subjects. Topical application of MAb to SA I/II prevented colonization of both artificially implanted exogenous strains of S. mutans, as well as natural recolonization by indigenous S. mutans. The properties of the protective MAb were then investigated and the epitope specificity within the SA I/II molecule was found to be essential but not the isotype specificity of the immunoglobulin (Ig). The requirement for complement activating and the phagocyte binding sites of the Fc fragment of MAb was not essential, as the F(ab')2 fragment of the MAb was as protective as the intact IgG, but the Fab fragment failed to prevent recolonization of S. mutans. Prevention of recolonization was specifically restricted to S. mutans, as the proportion of other organisms, such as S. sanguis, failed to show a significant change. The surprising feature of these experiments was that protection of re-colonization of S. mutans lasted up to 2 years, although MAb was applied for only 3 weeks and functional MAb was detected on the teeth only 3 days following application of the MAb. The long-term protection could therefore not be accounted for by a persistence of MAb on the teeth, but may be due to a shift in the microbial balance in which other bacteria occupy the ecological niche vacated by S. mutans, resulting in colonization resistance to S. mutans. Gene cloning and sequencing the SA from S. mutans, S. sobrinus and S. sanguis identified a conserved region (residues 955-1213) which on Southern hybridization and partial DNA sequence analysis was also found in 19 alpha-haemolytic oral streptococci. The results suggest that the SA molecule may constitute a family of adhesins in oral alpha haemolytic streptococci.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1295337 TI - Delivery of antigens by recombinant avirulent Salmonella strains. PMID- 1295338 TI - Use of recombinant BCG as a vaccine delivery vehicle. PMID- 1295339 TI - Liposomes and conjugate vaccines for antigen delivery and induction of mucosal immune responses. AB - In this brief review, emphasis was placed on the effectiveness of liposomes as carriers/vehicles of soluble antigens and as adjuvants for use in oral vaccine development. Evidence was provided that oral administration of antigen in liposomes resulted in a mucosal response which was higher than that obtained when the oral vaccine consisted of antigen alone. Specific mucosal responses were enhanced by incorporating lipophilic MDP into the antigen/liposome vaccines. Antigens shown to be effective in inducing a protective mucosal response when given in an oral liposome vaccine were anti-idiotypic antibodies, purified S. mutans GTF, CHO and Ag I/II. Evidence is also provided that CTB may be an effective oral adjuvant when coupled to proteins or peptides by either chemical or genetic methods. Further studies, however, will be required to characterize the effectiveness and safety of CTB in conjugate vaccines for inducing specific mucosal responses and to develop practical means to prepare oral liposome vaccines for use in humans. PMID- 1295340 TI - Peroral immunization with a cholera toxin-linked bacterial protein antigen and synthetic peptide. PMID- 1295341 TI - Peptomers as vaccine candidates. PMID- 1295342 TI - Molecular, immunological and functional characterization of the major surface adhesin of Streptococcus mutans. AB - In the 15 years since the last major NIH conference that dealt with anti-caries vaccines, we have learned much. Certainly, whole bacteria or bacterial fractions may not be proper immunogens due to the possibility of inducing tissue cross reactivity. Our own experience (van de Rijn et al., 1976) illustrates that pitfall. But even in the era of genetically engineered vaccines, we first must understand the biological functions of our chosen immunogen before employing that pure protein in a vaccine. Our recent work (Brady et al., 1991c) indicates that antigen P1, a ubiquitous protein found on several oral streptococci, may possess different, but possibly overlapping, functional domains influencing reactions with fluid-phase salivary agglutinin (aggregation) versus fixed agglutinin (adherence). A proper vaccine would induce antibodies against the latter domain(s) thereby retarding colonization. An improper vaccine that induces antibodies against aggregation-related domains on P1 would lessen the host's ability to clear those bacteria from the oral cavity. After carefully identifying appropriate functional domains and obtaining sub-clones of the larger gene that yield truncated polypeptides typical of adherence-specific regions that are also immunogenic, we may be in a position to create the most effective vaccine. In studies employing the polymerase chain reaction (PCR) and standard cloning procedures, we have already begun to produce such polypeptides. Once a library of polypeptides is assembled, they may be tested for functional activity and for lack of induction of cross-reactivity with nonpathogenic streptococci (i.e., S. gordonii). Certain of these recombinant-specified polypeptides could serve as the basis for an anti-caries vaccine. Alternatively, peptides may be synthesized that resemble these sub-molecular regions for use in a vaccine or as competitive inhibitors of adherence but not aggregation. Clearly, a vaccine against dental caries remains a real possibility for the future. PMID- 1295343 TI - Reactive antigens of the periodontopathic bacterium. Actinobacillus actinomycetemcomitans. PMID- 1295344 TI - Bacterial diseases of the oral tissues. PMID- 1295345 TI - Vaccine development: progression from target antigen to product. PMID- 1295346 TI - Significance of immune responses to oral antigens in dental diseases. PMID- 1295347 TI - Laboratory correlates of protection and protective immunity to Bordetella pertussis. PMID- 1295348 TI - Challenges and opportunities in vaccine research. PMID- 1295349 TI - Mucosal immunity to vaccines: current concepts for vaccine development and immune response analysis. PMID- 1295350 TI - Oral virus infections: the potential for gene transfer in treatment and prevention. PMID- 1295351 TI - Bacterial mucosal vaccines. PMID- 1295352 TI - A general overview of viral vaccine development. PMID- 1295353 TI - An update on the "Jennerian" and modified "Jennerian" approach to vaccination of infants and young children against rotavirus diarrhea. PMID- 1295354 TI - IgA1 proteases and host-parasite relationships in the oral cavity. PMID- 1295355 TI - Transport of IgA immune complexes across epithelial membranes: new concepts in mucosal immunity. PMID- 1295356 TI - Effect of mucosal microenvironment on immune response to viruses. PMID- 1295357 TI - Bone and joint disease progression: detection, imaging and quantification. PMID- 1295358 TI - Antigen-induced late-phase airway obstruction in the guinea pig? AB - Hartley or Dunkin-Hartley guinea pigs (n = 136) were actively sensitized to ovalbumin or Ascaris suum protein by five different regimes. Specific airway resistance (sR(AW)) was measured in conscious animals by a plethysmographic procedure before, immediately following and at various intervals (up to 96 h) after aerosolized antigen or vehicle challenge. Each sensitization and challenge regime produced an immediate allergic response with positive responses (defined as a 2-fold increase in sR(AW)) in 78-100% of animals. Recovery from the immediate response followed by late-phase responses was observed in only two out of a group of four animals. The results failed to substantiate literature reports of a high incidence of late responses in the guinea pig at 4-8, 17-24 or 72 h after allergen challenge. PMID- 1295359 TI - Antigen-induced hyperresponsiveness to methacholine in ventilated, anesthetized guinea pigs. AB - Guinea pigs were actively sensitized to ovalbumin and exposed 2-3 weeks later to an aerosol of ovalbumin or saline. Changes in lung function were assessed 0.5, 1, 6, 24 and 72 h later by measuring the peak increase in pulmonary inflation pressure induced by i.v. methacholine during constant-volume ventilation. Responses to methacholine were significantly potentiated at 0.5, 1, 6 and 24 h but not at 72 h following exposure to antigen. Hyperresponsiveness to methacholine was maximal at 0.5-1 h and, in terms of magnitude, comparable to the early increase in airway reactivity found in mild asthmatics after allergen challenge. Whether the hyperresponsiveness to methacholine induced by antigen in the guinea pig can be attributed solely to an increase in airway reactivity or is due, at least in part, to decreased lung compliance requires further study. PMID- 1295360 TI - Adenosine-induced bronchoconstriction in an allergic rabbit model: antagonism by theophylline aerosol. AB - Recently, there has been an increasing interest in the involvement of adenosine as a mediator of allergic asthma. In the present study, we have employed an allergic rabbit model to study the airway responses to adenosine. The rabbit litter mates were injected i.p., within 24 h of birth, with ragweed pollen extract to preferentially produce ragweed-specific IgE. This allergic rabbit model demonstrates many clinical features of asthma similar to human allergic asthma. Aerosolized adenosine (0.156-10 mg/ml) caused a concentration-dependent bronchoconstriction. The normal rabbits (non-immunized) did not respond to adenosine within that concentration range. Theophylline significantly inhibited the adenosine-induced bronchoconstriction. These early studies suggest that adenosine differentiated asthmatic airways from normal airways and adenosine induced bronchoconstriction in this model was mediated through specific cell surface receptor(s). PMID- 1295361 TI - Modification of allergen-induced airway obstruction and bronchial hyperresponsiveness in the allergic rabbit by theophylline aerosol. AB - The effects of theophylline on allergen-induced airway obstruction and bronchial hyperresponsiveness were investigated in allergic rabbits. This allergic rabbit model was developed in our laboratory and stimulates the human model of allergic asthma in several aspects. Four allergic rabbits with hyperreactive airways were challenged with ragweed to elicit early- and late-phase asthmatic responses and subsequent increased airway responsiveness. Two to three weeks later, the rabbits received theophylline (5 mg/ml, nebulized for 3 min) prior to a second allergen challenge. Theophylline significantly inhibited the allergen-induced early- and late-phase asthmatic responses by 38% (P < 0.05) and 49% (P < 0.05), respectively. Further theophylline inhibited the allergen-induced increase in lung resistance by 42% (P < 0.05) during the late-phase responses. Theophylline also inhibited the allergen-induced bronchial hyperresponsiveness by 39% (P < 0.05) at 24 h. These data suggest a potential anti-inflammatory effect of theophylline in preventing allergen-induced asthmatic responses and bronchial hyperresponsiveness. PMID- 1295362 TI - Quantitation of eosinophil Major Basic Protein cytotoxicity to rodent respiratory epithelium. AB - Eosinophil Major Basic Protein (MBP) may be a potent effector in damaging airway epithelium and inducing acute (2-3 h) hyperresponsiveness to agonists in primates. Accordingly, interactions between human eosinophil MBP and guinea-pig airway epithelium were quantitated biochemically. MBP was extracted from human eosinophils and purified by size-exclusion HPLC. This resulted in a single protein band on electrophoresis, which cross-reacted with antisera raised to peptides derived from the predicted sequence of human MBP. This human MBP caused modest, but statistically significant, damage to respiratory epithelium (16.4% increase in efflux of 51Cr from guinea-pig tracheal rings) after 3 h of incubation with 10(-4) M concentration, but not with lower concentrations. These data demonstrates that MBP cytotoxicity to intact epithelium can be rapidly measured in vitro, and suggests that rodent airway epithelium may be relatively resistant to the cytotoxic effects of MBP. PMID- 1295364 TI - Chasing the elusive animal model of late-phase bronchoconstriction: studies in dogs, guinea pigs and rats. AB - Antigen inhalation in sensitized dogs, guinea pigs and rats resulted in a marked, late-phase, eosinophil-rich, influx of inflammatory cells into the bronchial lumen. Attempts to demonstrate an associated late-phase bronchoconstriction were disappointing. We were unable to demonstrate a late-phase bronchoconstriction in either rats or dogs, even when dogs were pretreated with metyrapone to reduce blood cortisol levels. In ovalbumin-sensitized guinea pigs, challenged with low doses of ovalbumin, we observed an immediate bronchoconstriction, a late-phase bronchopulmonary eosinophilia but no late-phase bronchoconstriction. However, inhalation of very high doses of antigen in mepyramine-treated sensitized guinea pigs did induce a moderate late-phase bronchoconstriction. PMID- 1295363 TI - Multiple antigen challenge produces pulmonary eosinophilia but not pulmonary hyperresponsiveness in actively sensitized guinea pigs. AB - Exposure of actively sensitized boosted guinea pigs to aerosolized antigen, 3 times on alternate days, produced pulmonary eosinophilia but not pulmonary hyperresponsiveness to methacholine Cl measured 3 days after the last antigen challenge. These data suggest that the presence of large numbers of eosinophils in the airways and tissues of the lungs is not sufficient to produce nonspecific pulmonary hyperresponsiveness. These data also suggest that actively sensitized and boosted guinea pigs respond differently to repeated antigen exposure than do asthmatics or wild caught allergic cynomolgus monkeys. PMID- 1295365 TI - Repeated aeroallergen challenge induces lung dysfunction but not bronchial hyperresponsiveness in conscious guinea pigs. AB - Adult male Hartley-strain guinea pigs were sensitized by 10 min exposure to aerosolized 1% ovalbumin (OA; 10 mg/ml in normal saline containing 4% heat-killed B. pertussis vaccine and 0.02% antifoam B emulsion). One week after sensitization, animals were placed in an exposure chamber and challenged (nebulized OA 0.5%) until each animal showed labored breathing. Maximal exposure time was 10 min. Diphenhydramine (20 mg/kg, i.p.) was given 1 h before each OA challenge to protect the animals from bronchospasmic death. Antigen challenge was repeated twice a week for 2 weeks. The specific airway resistance (sR(aw)) changes in response to increasing concentrations of aerosolized acetylcholine (Ach) were determined. The data obtained in this study demonstrated that repeated antigen challenge produced a significant bronchial tone i.e. an increase in sR(aw) and a decline in specific airway conductance (sG(aw)) and failed to induce bronchial hyperreactivity to aerosolized acetylcholine (Ach) in conscious guinea pigs. PMID- 1295366 TI - Characterization of aeroallergen-induced dyspnea in unrestrained guinea pigs by bias-flow-ventilated whole body plethysmography. AB - Aeroallergen-induced dyspnea in guinea pigs was associated with an increase in amplitude in the box pressure fluctuations (212%) and pseudo-flow signal (604%) and an 80% decline (from 0.19 to 0.04 s) in relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value). All of these lung dysfunction changes were highly significant (P < 0.001). Pyrilamine (1 mg/kg, p.o., -2 h) inhibited dyspnea (delta P and delta F) by 50-53%. This technique allows quantitative analysis of allergic dyspnea in conscious, unrestrained guinea pigs. PMID- 1295367 TI - Pulmonary responses of the guinea pig to inhaled A23187: a brief review. AB - The pulmonary effects of inhaled A23187 are reviewed. Guinea pigs challenged with this divalent cationic ionophore rapidly develop airway obstruction, which is maintained for at least 4 h. Pulmonary inflammation and increased airway responsiveness are also observed. Pharmacologic manipulations suggest that these actions are due to the release of multiple mediators. We have found A23187 challenge to be valuable as an approach for testing potential asthma drugs. PMID- 1295368 TI - Lack of late-phase airway responses in conscious guinea pigs after a variety of antigen challenges. AB - Guinea pigs were actively sensitized by parenteral injections of ovalbumin (OA), house dust extract (HD) or Ascaris suum extract (As) in a variety of multidose regimens. At least 3 weeks after the initial sensitization injection, aerosols of the appropriate antigen were administered to conscious guinea pigs in a double chamber body plethysmograph. OA elicited the most consistent and intense bronchoconstriction (BC) as measured by decreases in specific airway conductance (sGAW). The airway responses to As were clearly separable into responders and nonresponders. HD produced essentially no BC. However, intense lacrimation and rhinorrhea occurred in all HD-sensitized, but not unsensitized, animals. No late phase changes in sGAW or increased reactivity to other spasmogens were seen up to 8 h after any antigen challenge. Eosinophil influx of magnitude similar to that measured by 24 h post-antigen bronchoalveolar lavage (BAL) occurred with all the three antigens. Animals which did not bronchoconstrict to As experienced an equal or greater pulmonary eosinophilia as airway responders. The present data with HD and As suggest that acute BC in response to antigen provocation is not a prerequisite for the eventual pulmonary eosinophilia. The lack of late-phase airway reactions in these models raises a doubt in the direct extrapolation to airway responses in allergic human asthma. The acute lacrimation and rhinorrhea to HD may suggest utility as a model of allergic rhinitis. PMID- 1295369 TI - Comparison of the airway hyperreactivity produced by single and multiple antigen exposures in sensitized guinea pigs. AB - Chronic airway hyperreactivity is a hallmark feature of asthma, but animal models of airway hyperreactivity often utilize a single antigen challenge. Therefore, we compared the airway hyperreactivity produced by single and multiple antigen challenges in ovalbumin-sensitized guinea pigs. Significant (2-fold) leftward shifts in dose-response curves for i.v. methacholine- or LTD4-induced bronchoconstriction in anesthetized and ventilated animals occurred 24 h following a single ovalbumin challenge. This nonspecific airway hyperreactivity was prevented by pretreatment with ketotifen or dexamethasone. However, airway hyperreactivity was no greater 24 h following the last of 3 daily antigen challenges than after 1 challenge and was absent 72 h following one antigen challenge. These results raise concern over the similarity of antigen-induced airway hyperreactivity in guinea pigs to the chronic airway hyperreactivity in asthmatics. PMID- 1295370 TI - Acute hypersensitivity to aerosolized histamine induced by aerosolized ovalbumin in guinea pigs. AB - Acute airway hyperresponsiveness can be induced after exposure to aerosolized ovalbumin in sensitized guinea pigs. The purpose of the present studies was to determine if "pro-inflammatory agents" would potentiate and prolong antigen induced pulmonary hyperresponsiveness to histamine in guinea pigs. Guinea pigs were sensitized to aerosolized ovalbumin by exposing them to a 3 min aerosol, generated ultrasonically from a 10% ovalbumin solution on day 0 and day 7. On day 13 the guinea pigs were exposed to a 3 min aerosol of deionized water or a pro inflammatory agent (1 microgram/ml PAF, 1 mg/ml LPS, or 4% B. pertussis vaccine). Twenty-four hours later, on day 14, the conscious guinea pigs were challenged with a 3 min aerosolized ovalbumin exposure (under isoproterenol cover) and the individual guinea pig responsiveness to aerosolized histamine was determined 2 and 24 h later in an anesthetized modified Konzett-Rossler preparation. Under these experimental conditions, ovalbumin challenge to sensitized guinea pigs produced only an acute hyperresponsiveness (about a 3-10-fold shift) to aerosolized histamine, which lasted less than 24 h. The pro-inflammatory agents neither potentiated nor prolonged the duration of the hyperresponsiveness. PMID- 1295371 TI - Specific temperature dependence of diamine oxidase activity and its thermal stability in the presence of polyvinylalcohol. AB - An inflexion point on the dependence of the swine kidney diamine oxidase activity upon the temperature was found at 40-43 degrees C, suggesting a conformational transition. The activation energies with putrescine as substrate calculated from the Arrhenius plots were 38.23 kcal/mol for the temperature interval 25-40 degrees C and only 15.14 kcal/mol for the range 45-60 degrees C. These values suggest two different conformations, one corresponding to the interval below 40 degrees C and another one between 43-60 degrees C, with an intermediate transitory form corresponding to the inflexion point at 40-43 degrees C. For various temperature decades within 10-60 degrees C, peculiar Q10 values in the range 1.37-3.00 (differing from the usual value Q10 = 2), were obtained. The non strictly Arrhenius curves, the activation energies and the inflexion point were quite similar with and without 0.05% polyvinylalcohol. This particular temperature effect found for swine kidney diamine oxidase is similar to the one reported for bovine serum amine oxidase. An increased enzyme thermal stability was obtained in the presence of high molecular weight polyvinylalcohol. PMID- 1295372 TI - Decreased histamine content and metabolism in mammary cancer tissue from C3H mice. AB - Histamine (HA) level and its metabolism in adenocarcinoma mammae, spontaneously growing cancer in C3H mice, were examined in relation to the type of tumor, intensity of tumor vascularization and the presence or absence of a secretory function. Histamine concentration being in mammary gland one of the highest among mammalian organs (418 nmol/g) was decreased by 90% in tumor (34 nmol/g). Similarly, histidine decarboxylase (HDC) activity dropped from approximately 7.6 pmol/min/g in normal gland to an undetectable level in adenocarcinoma mammae. Of the two main HA degrading enzymes, namely, diamine oxidase and histamine N-methyl transferase (HMT), only HMT could be detected in mammary gland, either healthy or neoplastic, and its activity was about 5-fold lower in tumor than in the control tissue (1 nmol/g/min vs. 5.2 nmol/g/min). The pattern of changes in histaminergic parameters evoked by the tumor was similar irrespective of the morphological type it represented, characteristics of its vascular bed or whether or not it showed secretory activity. PMID- 1295373 TI - Effects of ketotifen on airway responses to allergen challenge in the actively sensitized brown Norway rat. AB - The purpose of the study was to examine the effect of ketotifen on the airway responses and the recruitment of the inflammatory cells into the airways of sensitized rats after antigen challenge. Twenty-five Brown Norway rats, 7-9 weeks old, were actively sensitized to ovalbumin (OA) (1 mg s.c.) and Bordetella pertussis vaccine (10(9) bacilli i.p.). At 14 days after sensitization rats were anesthetized with urethane (1.1 g/kg i.p.) and intubated endotracheally. Aerosols of OA (5% W/V in saline for 5 min) were administered to control rats (Group A; n = 9), to a low-dose ketotifen group (Group B; 1 mg/kg PO; n = 8) and a high-dose ketotifen group (Group C; 10 mg/kg; PO for 10 days; n = 9). Pulmonary resistance (RL) was measured at baseline, and every 15 min for up to 8 h after OA. The magnitude of the early response was 241 +/- 51% in A (% baseline RL; mean +/- SE), and significantly less in B(119 +/- 7%) and C(131 +/- 16%) (p < 0.01). The late response was significantly lower in C than A but not B. The total cell number in bronchoalveolar lavage at 8 h after OA challenge was significantly higher in A than B and C (p < 0.01). The lymphocyte and eosinophil counts were reduced in B and C compared to A (p < 0.05). A positive correlation was found between the late response and total number of cells recovered in the BAL (r = 0.78) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295374 TI - Neutralization of the oedematogenic activity of Bothrops jararaca venom on the mouse paw by an antibothropic fraction isolated from opossum (Didelphis marsupialis) serum. AB - The pharmacological modulation of mice paw oedema produced by Bothrops jararaca venom (BJV) has been studied. Intraplantar injection of BJV (1-30 micrograms/paw) produced a dose- and time-related oedema, which was maximal 30 min after injection, reduced gradually thereafter and disappeared over 48 h. BJV heated at 100 degrees C for 5 or 15 min blocked local hemorrhage and caused partial inhibition of its oedematogenic activity. The BJV oedema was not inhibited by the anti-histamine meclizine, the inhibitor of histamine and serotonin, cyproheptadine, PAF-acether antagonist WEB 2170 or by the anti-leukotrienes C4/D4, LY 171883. Dexamethasone, aspirin, indomethacin, and the dual cyclooxygenase and lipoxygenase inhibitor BW 755C inhibited BJV-induced oedema indicating that arachidonic acid metabolism products via the cyclooxygenase pathway participate in its genesis and/or maintenance. The antibothropic fraction (ABF) (25-200 micrograms/paw) isolated from Didelphis marsupialis serum neutralized the oedema induced by the venom with and without heating, the hemorrhage induced by BJV and partially blocked the oedema induced by bradykinin and by cellulose sulphate. The oedema produced by histamine, serotonin, PAF acether or leukotriene C4 was not inhibited. PMID- 1295375 TI - Effect of clonidine on experimental brain edema in the rat. AB - Several experimental brain edema models are currently available for drug evaluation. Brain edemas are essentially vasogenic and/or cytotoxic, and eicosanoids are involved in the development of these edemas. Thus, a new model developed in our laboratory, which was obtained by phospholipase A2 intracerebral injection was used to study the antiinflammatory effect of clonidine. The copper wire edema model was chosen as reference. Edemas were evaluated by determining the swelling and Na+ and K+ tissue concentrations of each hemisphere. Drugs were administered intraperitoneally. Dexamethasone was the only drug to inhibit copper wire-induced edema, whereas indomethacin and clonidine as well as dexamethasone exhibited marked antiedematous activity in our model. The effect of clonidine, which could be inhibited by prior administration of yohimbine, suggests that central alpha 2-adrenergic stimulation is involved in reducing experimental brain edema. PMID- 1295377 TI - Comparative study of effects of cyclosporins A and G on collagen arthritis in mice. AB - The effects of the immunosuppressive agents cyclosporin G (CsG) and cyclosporin A (CsA) on collagen arthritis were compared in mice. When administered subcutaneously daily on days 0-13 after immunization with type II collagen, CsG and CsA were both capable of suppressing the development of collagen arthritis in mice as well as the immunological response to native type II collagen in a dose dependent manner. Histopathologically, no marked inflammatory lesions were observed in diarthroidal joints from mice treated with 100 mg/kg per day of CsA or 800 mg/kg per day of CsG. However, an analysis of dose response showed CsG to be 8 times less potent than CsA in inhibiting the development of arthritis. PMID- 1295376 TI - Anti-inflammatory properties of zinc protoporphyrin disodium (Zn-PP-2Na). AB - Anti-inflammatory properties of zinc protoporphyrin disodium (Zn-PP-2Na) were studied. Zn-PP-2Na exhibits anti-allergic action against type III and IV reactions (passive Arthus reaction in rats and tuberculin-induced footpad reaction in mice), but does not affect type I and II reactions (homologous passive cutaneous anaphylaxis in mice and reversed cutaneous anaphylaxis in rats). Zn-PP-2Na also clearly inhibits type II collagen-induced arthritis in mice. The agent inhibits general arthritis symptoms, anti-type-II collagen antibody production and type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice. Zn-PP-2Na, however, did not affect carrageenin-induced paw edema and histamine- and serotonin-induced skin reactions in rats. Zn-PP-2Na inhibits IL-1-induced mouse lymphocyte proliferation, but does not affect PMA induced O2- generation from guinea-pig neutrophil. These results indicate that Zn PP-2Na inhibits type II collagen-induced arthritis in mice due to the antagonism of IL-1 activity and the inhibition of DTH against type II collagen. PMID- 1295378 TI - Effect of adjuvant arthritis on the disposition of acebutolol enantiomers in rats. AB - Disease states such as arthritis may interact with the kinetics of beta-blockers. Acebutolol (AC) is a chiral beta-blocker which is available as a racemate. The beneficial properties of AC, however, is attributed mainly to the S-(+) enantiomer. The disposition of AC enantiomers and their active, chiral metabolites, diacetolol (DC) were examined after oral administration to healthy and adjuvant-induced arthritic (AA) female Sprague-Dawley rats. Arthritis was induced by tail base injection of Mycobacterium butyricum. Swelling of hind and forepaws were apparent in 10-16 days in AA but not controls. Control and AA rats were sacrificed at 0.5, 1, 2, 4, 6 and 8 h after a 25 mg/kg oral AC dose and blood was collected (n = 6). Significant three to tenfold increases in the initial plasma concentrations (0.5-2 h) of AC were observed in AA. Enantiomers were equally affected, thus AC S:R ratio was not changed. Higher plasma concentrations of the metabolite were only significant at 2 h. The ratio of DC:AC, however, was unaffected by AA. The DC S:R ratio was significantly decreased at 0.5 and 1 h in AA. The limited protein binding of AC (10%) was neither stereoselective nor affected by AA. Reduced intrinsic clearance in AA may be responsible for these observations. PMID- 1295379 TI - Immunodepressive activity of FCE 23762 on humoral and cell-mediated immune responses in normal mice: comparison with doxorubicin. AB - FCE 23762 (3' desamino-3'[2(s)methoxyl-4-morpholinyl]doxorubicin) is a new doxorubicin (Dx) derivative that has been selected for clinical testing for its favourable antitumor characteristics, which include efficacy on Dx-resistant tumors. Immunosuppression is an undesirable side-effect of anti-cancer chemotherapy and the therapeutic efficacy of Dx is probably also related to its low immunotoxicity. It was, thus, of interest to compare the effects of FCE 23762 and its parental drug on the immune responses. Both compounds were injected i.v. into healthy mice at equitoxic doses and according to different treatment schedules. Single doses of FCE 23762 and Dx, given concomitant or after the antigen, suppressed at the same degree and dose-dependently the primary anti-SRBC antibody response. Following a multiple treatment schedule after the antigen, FCE 23762 was less suppressive than Dx on both primary and secondary antibody production. Differently from Dx, that was completely inactive, FCE 23762 moderately inhibited DTH reaction to SRBC, only at the highest single dose tested or for repeated administrations given simultaneously or after priming. Both drugs were totally ineffective in delaying skin allograft rejection. Since spleen cellularity and ex vivo lymphocyte proliferation to Con A and LPS were similarly impaired by the two drugs, the differentiated immunodepressive activity of FCE 23762 and Dx cannot be merely associated to their cytotoxic and antiproliferative action. The hypothesis of a selective effect on different regulatory cell subsets and/or immune mechanisms is discussed. PMID- 1295381 TI - The retinal distribution of ganglion cells with crossed and uncrossed projections and the visual field representation in the opossum. AB - The retinal distribution of ganglion cells with crossed and uncrossed projections in the South American opossum, Didelphis marsupialis, was revealed by delivering HRP to one optic tract or to retinal targets of one hemisphere. The cells with uncrossed projections are restricted to the temporal retina, comprising 1/3 of the total retinal area, with a sharp transition at the naso-temporal boundary. Besides being distributed over the nasal 2/3 of the retina, cells with crossed projections are intermingled with those with uncrossed projections over the entire temporal retina. Quantitative analysis about the representation of the horizontal meridian on four specimens revealed that the maximum density of cells with uncrossed projections is on the average located at 3.2 mm (SD = 0.21), i.e. 34.8 deg, temporal to the optic disk, falling to 10% at 2.1 mm (SD = 0.14) or 22.8 deg. On the other hand, the peak for cells with crossed projections is more nasally placed at 1.8 mm (SD = 0.18), i.e. 19.6 deg. Between these two maxima, the site wherein the densities of cells with crossed and uncrossed projections are about equal is on the average about 2.7 mm (SD = 0.25) form the optic disk, i.e. 29.3 deg. This estimate supports the hypothesis that the retinal intersection of the vertical meridian lies within the region of split representation of crossed and uncrossed ganglion cells. In addition, it was observed that the opossum's retina has a large contingent of cells with uncrossed projections temporal to an eccentricity of 2.7 mm from the optic disk, where it represents roughly 2/3 of the ganglion cells. These data corroborate the relevance of the opossum as a non-primate model for visual work. PMID- 1295380 TI - Is granulocyte or endothelial cell activation responsible for the initiation of granulocyte recruitment during acute inflammation? PMID- 1295382 TI - [Acute toxicity of ammonia in the production process of postlarvae of Penaeus paulensis Perez-Farfante, 1967]. AB - Larval shrimp Penaeus paulensis showed a tendency to decrease in ammonia tolerance as the larva metamorphosed from nauplius to postlarvae stage. The 24-h LC50 were 4.04, 1.70, 2.72, and 1.42 mg/l NH3-N on nauplii, zoea, mysis and postlarvae, respectively. The zoea stage and the initial postlarvae substages were very susceptible to ammonia. The 96-h LC50 values on zoea and postlarvae were 0.69 mg/l and 0.32 mg/l, against 0.80 mg/l NH3-N on mysis. The eggs of Penaeus paulensis were very affected by ammonia, which provoked a progressive decrease in the hatching rate and induced morphological deformities in hatched nauplii. A "safe level" of ammonia was estimated at 0.032 mg/l NH3-N on the basis of 24-h LC50 for eggs. PMID- 1295383 TI - [Acute toxicity of ammonia to Artemia sp]. AB - The acute toxicity of total ammonia-N, (NH3 + NH4+), and un-ionized ammonia-N, NH3-N, on newly hatched Artemia nauplii and Artemia adults was measured in 24, 48, 72, and 96-h semi-static bioassays system. There was a significant difference (P < 0.05) in medial lethal concentrations (LC50) obtained during the tests. The LC50 values on nauplii ranged from 650 mg/l, in 24-h, to 399.1 mg/l total ammonia N, in 96-h, while the LC50 values on adults ranged from 1290.4 mg/l to 600.5 mg/l total ammonia-N, in the same period. Two methods for calculations of un-ionized ammonia toxicity are analyzed and discussed. PMID- 1295385 TI - Cold agglutinin disease. PMID- 1295384 TI - [Immunological origin of autoimmune cytopenias]. PMID- 1295387 TI - Idiopathic thrombocytopenic purpura, autoantibodies, autoantigens. An overview. PMID- 1295388 TI - [Interactions between human immunodeficiency virus and immune system in lymphoid organs]. PMID- 1295386 TI - T cell receptor and alloimmune thrombocytopenias: a model for autoimmune diseases? PMID- 1295389 TI - [Use of polymerase chain reaction (PCR) for the diagnosis of hepatitis C virus infections]. PMID- 1295390 TI - [Central nervous system lesions associated with human immunodeficiency virus infection]. PMID- 1295391 TI - Cardiomyopathy: a post-viral autoimmune disease? PMID- 1295392 TI - Antiphospholipid syndrome. The clinician's point of view. PMID- 1295393 TI - The autoimmune basis of ANCA positive systemic vasculitis. PMID- 1295394 TI - [Anti-neutrophil cytoplasm antibodies. From biology to clinics]. PMID- 1295396 TI - Interview with Graham Hughes. What is going to happen tomorrow in the field of anti-phospholipid antibodies?. Interview by P. Youinou. PMID- 1295395 TI - Ear, nose and throat manifestations in c-ANCA-positive vasculitides. Diagnostic, therapeutic and pathogenetic implications. PMID- 1295397 TI - Interview with Robert Schwartz. What is going to happen tomorrow in the field exploring the relationship between viruses and autoimmunity?. Interview by P. Youinou. PMID- 1295398 TI - Active clusters and concentration--effect dependencies for biologically active substances. PMID- 1295399 TI - General principles of protecting people from arthropod pests. PMID- 1295400 TI - Interpretation of a model for a DDT-treated population of Ixodes persulcatus. I. Susceptibility of Ixodes persulcatus P. Sch. (Acarina, Ixodidae) to DDT in different developmental stages and physiological states. PMID- 1295401 TI - Interpretation of a model for a DDT-treated population of Ixodes persulcatus. II. Factors contributing to effectiveness of acaricide application. PMID- 1295402 TI - Toward the constructive theory of human social behavior. I. General principles. PMID- 1295403 TI - Toward the constructive theory of human social behavior. II. Consumer behavior. PMID- 1295404 TI - Toward the constructive theory of human social behavior. III. Labor behavior with due regard for consumption. PMID- 1295405 TI - Toward the constructive theory of human social behavior. IV. Labor behavior under fixed remuneration. PMID- 1295406 TI - Toward the constructive theory of human social behavior. V. Labor behavior under piecework pay. PMID- 1295407 TI - Maturation of the filaria Litomosoides sigmodontis in BALB/c mice; comparative susceptibility of nine other inbred strains. AB - When inoculated subcutaneously, the infective larvae of L. sigmodontis undergo complete development and produce a patent microfilaraemia in mice of the BALB background (BALB/c, BALB/K and BALB/B, with respectively the H-2d, H-2k et H-2b haplotypes). The most susceptible strain is BALB/c with all mice harbouring adult filariae and 47% of mice presenting with a patent microfilaraemia. Mice with the B10 background (B10, B10Br and B10D2, with respectively the H-2b, H-2k et H-2d haplotypes) are almost completely resistant to infection. Adult filariae were recovered from all mice of the CBA/Ca, CBA/HN, C3H/HeN, DBA/2N strains. However, the site and structural development of the parasite varied in each strain. Absence of microfilaraemia is associated with absent or abnormal spicules, reduced number of female filariae and small size of female filariae. These results show that the Major Histocompatibility Complex only modulates the developmental pattern of filariae within the limits imposed by background genes. Male CBA/HN and C3H/HeN were more susceptible to infection than female mice. Inverse phenomenon was observed with strains BALB/c; and, no host sex effect was seen in DBA/D2N. PMID- 1295408 TI - Recertification. PMID- 1295409 TI - A survey of sexual behaviour of Singaporeans. AB - In order to plan education programmes against sexually transmitted diseases (STDs) and HIV infection, a population-based survey on partner relations was conducted on 2,115 Singaporean men and women aged between 15 and 49 years. Of the 605 (60.1%) sexually experienced men and 647 (58.3%) sexually experienced women, 510 (84.3%) men and 644 (99.5%) women were married. Of the marrieds, 465 (76.9%) men and 638 (98.6%) women had their first sexual encounter with the person who was or later became their spouse. Of the sexually experienced men, 97 (16%) engaged in casual sex in the previous year, of which 76 (78.4%) were encounters with commercial sex workers. Of these encounters 55 (72.4%) were unprotected or partially protected by condoms. A history of casual sex in the previous four weeks was given by 18 men, of whom 14 (77.8%) were married. Nine (64.3%) of these married men had sex concurrently with both their wives and commercial workers. Persons at high risk were those who started sexual activity early, unmarried, sexually active men with no or low education, and persons who travelled. Of the sexually experienced respondents, 1,242 (99.2%) had heard about condoms, and 431 (34.4%) were currently using them as contraceptive devices. Attitudes towards condoms and willingness to use them to prevent STDs and HIV infection were favourable. Men were more permissive in their attitudes towards sex. The level of permissiveness in men and women was not corroborated by their reported behaviour, an indication of either under-reporting and/or a disparity between attitude and practice. PMID- 1295410 TI - Clinical aspects of a successful embryo cryopreservation programme from IVF cycles in Singapore General Hospital. AB - An analysis in November 1991 showed a successful cryopreservation programme between May 1989 and October 1991 in Singapore General Hospital. This programme has resulted in 9.1% more pregnancies in addition to those from conventional in vitro fertilisation (IVF) methods, increasing pregnancy rates during the same period, from 27.8% per IVF cycle to 36.9% per cycle. The current policy is to transfer 3 fresh embryos in the IVF cycle and freeze the remainder using a modified Testart's method. Clinical factors that influence the success rate include the number of embryos transferred, stage of development of embryos and genital tract infections. Age of patient and grade of embryos did not seem to have affected pregnancy rates. Patients with anovulatory cycles enjoy similar pregnancy rates using a regulated cycle regime for frozen-thawed embryo transfer. PMID- 1295411 TI - Rheumatoid arthritis in Singapore: carpal predominance and lower incidence of erosive changes. AB - Radiographs of the hand and wrists in 33 patients with a diagnosis of classic or definite rheumatoid arthritis were reviewed. The mean duration of disease was about five years. A scoring system for quantitative analysis was used to assess the presence and severity of erosions, joint space narrowing and deviation of joint alignment. No radiological abnormality was seen in 30% of patients while in another 30%, only minor radiological changes were seen. Moderate to severe radiological abnormality was seen in only 40% and in this group of patients all showed more severe disease in the wrists than in the finger joints. Erosions in the fingers were only seen in 21% of patients and erosions in the wrists were present in 57%. Previous reports have indicated that disease in the wrists can be more severe than the hands in up to 60% while the incidence of erosions can be expected to range from 40% at 3 months to 95% at 10 years. Although the sample size in this study is small, the findings suggest that the radiological pattern of rheumatoid in the hands in Singapore is quite different from that classically described in temperate countries as the incidence of erosions appears lower while disease in the wrists can be expected to be more severe than in the fingers in almost all cases. The usual radiological criteria used to aid diagnosis of the disease may not be applicable. PMID- 1295412 TI - A cadaveric study of the potential damage in arthroscopic examination of the temporomandibular joints. AB - An arthroscopic study on 22 temporomandibular joints in 13 cadavers was undertaken. Dissections were carried out to correlate the arthroscopic with macroscopic findings in the joints. Iatrogenic damage to the temporomandibular joints and their surrounding tissues was also examined. Correlation between arthroscopy and macro findings was 91.0%. There was no damage to the facial nerve and superficial temporal vessels. Iatrogenic damage to the temporomandibular joint included scuffing of the articular surfaces of the glenoid fossa and articular eminence (31.8%), scuffing of the condylar articular surface (9%), one disc perforation (4.5%) and one perforation of the medial capsule (4.5%). Prevention of iatrogenic injuries is discussed. PMID- 1295413 TI - Benign lower jaw tumours and their management: a ten year experience in Nigeria. AB - Lower jaw tumours in Nigeria often grow to enormous size. A high cure rate can be achieved by wide excision of the tumours and bone grafting. Of 23 patients who underwent mandibular reconstruction in Enugu, Nigeria, over a ten year period, loss of bone graft occurred in three patients (14.28%), but no recurrence of tumour was noted over a follow-up period ranging from 2-12 years. An acceptable aesthetic and functional result followed bone grafting in most cases. PMID- 1295415 TI - A double-blind, randomised, cross-over study comparing the 50g OGTT and the 75g OGTT for pregnant women in the third trimester. AB - There is little consensus in the conduct and interpretation of the oral glucose tolerance test (OGTT) in pregnancy. In Singapore much data has been accumulated about the 50g OGTT while the converse is true of the 75g OGTT. A double-blind, randomised, crossover study of 56 subjects in the third trimester was conducted to compare both glucose challenges to determine if there was a difference in glucose handling in the context of a two hour OGTT. A significant difference (p < 0.001, t = 5.76) was found at two hours where the mean glucose concentrations were 5.2 +/- 0.8 mmol/L and 6.2 +/- 1.4 mmol/L for the 50g and 75g OGTT respectively. These findings suggest that the 75g OGTT is potentially more effective in unmasking pregnant subjects with impaired glucose tolerance. PMID- 1295414 TI - Renal bone disease in patients on haemodialysis: biochemical and radiological assessment. AB - Renal bone disease is an important cause of morbidity in patients on dialysis. The prevalence of renal bone disease, especially aluminium related bone disease, has not been studied in the Singapore dialysis population. As such, we studied 45 haemodialysis patients for renal bone disease using biochemical and radiological parameters. Selected patients underwent a renal biopsy. There were 29 males and 16 females, mean (+/- SEM) age, 44.6 +/- 13.4 years. The duration of haemodialysis ranged from two months to ten years, mean 18.5 months. 75.4% of patients had hyperphosphatasemia, 24.4% had hypocalcemia and two patients had hypercalcemia. There was a wide range in the serum parathyroid hormone levels and 55.4% of patients had serum parathyroid hormone levels > 1000 pmol/L. Patients with symptoms and radiological abnormalities had significantly higher serum parathyroid hormone and alkaline phosphatase levels than those without (P < 0.005). The desferrioxamine infusion test was positive, with an increment in serum aluminium (DL) > 100 mg/L in five patients. Skeletal survey was positive for renal bone disease in 24.4% of patients. There was a significant correlation between the serum parathyroid hormone level, DA1 and the duration of dialysis (r = 0.752, p < 0.001 and r = 0.837, p < 0.001 respectively). There was no correlation between serum parathyroid hormone, calcium, phosphate levels and DA1. The serum haemoglobin concentration and ferritin levels did not show a correlation with DA1. Bone biopsy revealed hyperparathyroid bone disease in two patients, aluminium-related bone disease in one patient and mixed uraemic osteodystrophy in one patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295416 TI - An assessment of serum lipid and lipoprotein levels in patients with ischaemic heart disease. AB - A total of 166 patients who had one or more attacks of myocardial infarction and those with angina pectoris, forty-five relative of 18 hyperlipidemic survivors of ischaemic heart disease, and 330 healthy persons (controls) were investigated for serum lipid profiles. Fifty-six of the 166 patients were hyperlipidemic. The commonest abnormalities in lipoproteins were Types IIa, IIb and IV. 75.5% of the 45 relatives investigated were hyperlipidemic. The familial studies showed that hyperlipidemias occurred in the family members of persons with ischaemic heart disease suggesting that hyperlipidemia could play an important role in predisposing familial clustering of coronary heart disease. A family history of heart disease may be a useful marker for identifying persons who are more likely to have high levels of blood lipids for possible treatment. PMID- 1295417 TI - Pattern of dermatophyte infection in Singapore. AB - Dermatophyte infection is the fourth commonest skin disorder seen in the National Skin Centre in Singapore. A prospective study was carried out from June 1990 to March 1991 to determine the epidemiology and pattern of dermatophyte infections seen in this centre. Two hundred patients who had a clinical diagnosis of dermatophyte infection and confirmed by direct microscopy were included into the study. Cultures for dermatophyte were done on Sabouraud's dextrose agar with chloramphenicol and cycloheximide. There were 148 male and 52 female patients, of whom 146 (73%) had a positive culture from one or more sites. One hundred and thirty-nine (95.2%) patients had dermatophyte infection while the remaining seven (4.8%) patients had non-dermatophyte infection. The sites involved were the groin (92 patients), feet (52 patients), trunk (26 patients), hands (18 patients), face (9 patients), legs (9 patients), scalp (8 patients) and axilla (7 patients). The commonest dermatophyte isolated was Trichophyton rubrum (81/139). It was also the commonest organism isolated in all the sites except the scalp. The other dermatophytes grown were, in order of frequency, Trichophyton interdigitale (21/139), Epidermophyton floccosum (19/139), Trichophyton mentagrophytes (9/139), Microsporum ferrigineum (4/139), Microsporum canis (4/139) and Microsporum gypseum (1/139). Scalp infections occurred in children and were due either to Microsporum canis or Microsporum ferrigineum. The organisms isolated in our study were either ubiquitous or common in the Asia-Pacific region indicating that certain dermatophytes are more prevalent in certain geographical regions. PMID- 1295418 TI - Myopia and educational attainment in 421,116 young Singaporean males. AB - Data of 421,116 Singaporean males aged 15 to 25 (mean 17.75) years who underwent compulsory medical examination in 1974-84 and 1987-91 were used to estimate the prevalence of myopia and to study the correlation between the prevalence and severity of myopia and educational attainment. The estimated myopia prevalence rate was 26.3% in 1974-84 and 43.3% in 1987-91. This rise in the rate was accompanied by an increase in the proportion of males who achieved higher levels of education over the same period. The overall myopia prevalence rate was 30.4%. Both the prevalence and severity of myopia were higher as the level of education attained increased. The myopia prevalence rate was 15.4% in males with no formal education and increased steadily through groups with intermediate education to 65.2% among those with GCE 'A' level education, 57.5% among diploma holders and 65.1% among university graduates in 1987-91. Seventy out of 173 (40%) myopes with no formal education compared to 1035 out of 1612 (64%) myopes with university degrees had unaided visual acuity worse than 6/60 in 1987-91. Our findings confirm indications from other sources that the association between the prevalence and severity of myopia and education attainment is real. A combination of genetic and environmental factors may be the cause of this association. PMID- 1295419 TI - A descriptive study of emergencies admitted to a surgical department. AB - A study was undertaken to evaluate the pattern of emergency admissions and their management by the surgical firm in a medium size (700 beds) general hospital. Over a three month period, 258 patients were admitted to one surgical team that was on take every third day. All patients were entered into a protocol that was updated daily by a registrar. In four (13.3%) of the 30 days on take, patients had to be referred to a nearby hospital due to shortage of emergency beds. The accuracy of diagnosis by the Accident and Emergency (A&E) resident, surgical resident and surgical team were 75.7, 77.2 and 88.4% respectively. The mean delay before attendance by an intern after admission was 47 (SD +/- 29) mins. Forty four (17%) of these admissions were probably unnecessary. A further 22 (8.5%) patients had to be referred to other disciplines, indicating an initial wrong diagnosis. A substantial number of investigations were unnecessarily done on an emergency basis. Ninety-three (36.0%) patients required surgery. The median duration of hospital stay was three days. The overall morbidity was 4.2% and mortality 1.2%. The study was valuable in revealing the deficiencies in the existing emergency service; leading to new proposals to achieve our ultimate aim of providing high quality patient care. PMID- 1295420 TI - An investigation of solvent-induced neuro-psychiatric disorders in spray painters. AB - An index case of chronic toxic encephalopathy is described in a 28 year old male spray painter with eleven years of exposure to solvents at work. The patient had progressive affective symptoms following repeated past episodes suggestive of acute solvent intoxication. He also showed impaired performance on tests of auditory memory, perceptual speed, visual scanning, and manual dexterity, as well as electromyographic evidence of prolongation of distal terminal latency and slowing of conduction velocities. The case investigation was followed up with an epidemiological study of the factory where he worked, to determine if other spray painters might have similar excessive complaints of neuropsychiatric symptoms and/or objective neurobehavioural deficits. This involved 15 other male spray painters employed for at least five years, and a sex- and age-matched group of 15 control workers not exposed to solvents. The spray painters reported significantly more numbers of neurobehavioural symptoms than the controls. There were little differences in neurobehavioural test results, except for aiming test (psychomotor co-ordination) and Benton visual retention test (visual memory). Spray painters with four or more neurobehavioural symptoms also performed more poorly on Digit Symbol (perceptual speed) compared with those with less number of symptoms. The epidemiological results provide strong circumstantial basis for the diagnosis of chronic toxic encephalopathy in the patient, and also indicates a need for vigilance of the hazards of central nervous system disorders in workers with chronic exposure to solvents in Singapore. PMID- 1295421 TI - Obstetric admissions to the intensive care unit--a retrospective review. AB - A five-year retrospective study of obstetric admissions to the Surgical Intensive Care Unit (SICU) in the National University Hospital, Singapore was carried out with the aim of determining the incidence, causes and outcome of these admissions. Most of the patients were admitted following emergency caesarean sections. Obstetric complications was the reason for admission in 56.8% with hypertensive disease of pregnancy being the major cause and haemorrhage accounting for the rest. Anaesthetic complications accounted for 21.6% of admissions and these included difficult intubation, aspiration pneumonitis, cardiac arrhythmias and respiratory depression. Medical complications due to cardiovascular disease, autoimmune disease and malignancy also accounted for 21.6% of admissions. Only 37 out of 16264 deliveries (0.22%) required intensive care support. The median of duration of stay was one day. PMID- 1295422 TI - The management of spasticity--a review of options available in rehabilitation. AB - The author gives a literature review of the management of spasticity carried out. Physical agents used such as ice, heat and vibration are described. Methods used by physical therapists are discussed. Drugs most commonly used in the treatment of spasticity are Diazepam, Baclofen and Dantrolene. Phenol has been used by injection into motor points, peripheral nerves and intrathecally. Other drugs that have been used are also discussed. Neurosurgical procedures include neurectomies, neurotomies, rhizotomies and more radical procedures such as myelotomies and cordectomies. Orthopaedic procedures involve muscle and tendon lengthening, release of contractures and tendon transfers. Surgery is discussed in terms of function. In considering the options, available care must be taken to achieve and maintain optimal functional level. PMID- 1295423 TI - Urinary symptoms and urodynamic diagnosis of patients in one geriatric department. AB - Fifty five patients between 65 and 89 years old who had their urinary problems assessed by urodynamics study were reviewed. The most common urinary symptom among males was urge incontinence, while retention and urge incontinence occurred with equal frequency among females. The commonest cause of retention in males was bladder outlet obstruction, while atonic neurogenic bladder was the most common cause in females. Urge incontinence was strongly associated with an unstable bladder, small bladder volume and Parkinson's disease. Retention of urine, and an atonic neurogenic bladder strongly correlated with diabetes mellitus. Three patients (out of 31) with unstable bladders also had detrusor external sphincter dyssynergia. Of these, two had Parkinson's disease. Although three patients were thought to have stress incontinence after history and physical examination, only two had stress incontinence with detrusor instability on urodynamic studies. The last patient had atonic bladder with overflow. PMID- 1295424 TI - Massive bleeding per rectum from a caecal pregnancy. AB - An unusual case of massive bleeding per rectum caused by erosion into the caecum of placental tissue from an ectopic pregnancy is presented. Despite its rarity, abdominal pregnancies may have to be considered in sexually active fertile women presenting with difficult torrential bleeding from the lower gastrointestinal tract. PMID- 1295425 TI - Polyneuropathy following intra-muscular sodium aurothiomalate for rheumatoid arthritis--a case report. AB - A patient with rheumatoid arthritis developed rapid onset of peripheral neuropathy whilst on treatment with intra-muscular (IM) gold (Sodium Aurothiomalate). At the time of admission, the arthritis was relatively quiescent. Electromyogram showed evidence of sensorimotor polyneuropathy. Investigations excluded other causes of polyneuropathy. Sural nerve biopsy did not reveal inflammation or vasculitis. The patient's condition improved after cessation of gold therapy. Gold induced neuropathy should be considered in a patient with rheumatoid arthritis who presents with polyneuropathy while on gold therapy. PMID- 1295426 TI - Tracheal rupture from incorrect positioning of endotracheal tube. AB - Significant ischaemic tracheal damage from endotracheal intubation is uncommon when the lateral wall pressure exerted by the cuff does not exceed the mean capillary perfusion pressure of the mucosa. This is facilitated by the modern endotracheal tubes with high-volume-low-pressure cuffs. We report a case of tracheal rupture due to an incorrectly positioned softcuffed tube. The need to review tube position radiologically and to make immediate adjustment cannot be overemphasised. PMID- 1295427 TI - Clear cell carcinoma of the lung--a case report. AB - Clear cell carcinoma of the lung is a rare entity. We report the first case seen locally. The patient is symptomatic, presenting with a large pulmonary tumour. Histologically, there were clusters of large tumour cells with ample clear cytoplasm and absence of mucin, glandular and squamous differentiation. Urine analysis, blood carcinoembryonic antigen level and abdominal CT scan were normal. PMID- 1295428 TI - Acute surgical abdomen in systemic lupus erythematosus--an analysis of 10 cases. AB - Gastrointestinal manifestations in a lupus patient may be due to different aetiologies such as vasculitis or a surgical condition. Problems of diagnosis are frequently encountered because the clinical presentations may mimic each other. We analysed ten lupus patients with acute surgical abdomen to identify the clinical, laboratory and radiological features that may aid in early diagnosis and management. Three patients with surgical abdomen had concomitant active lupus. Intra-abdominal sepsis and bleeding peptic ulcer disease constituted two major causes of laparotomies. Overt signs of peritonitis might not be present due to steroid masking effect. There were no specific clinical features, laboratory or radiological tests that could distinguish gastrointestinal vasculitis from acute surgical abdomen. Blood cultures, C-reactive protein and CT abdomen were useful adjuncts in the management of abdominal sepsis. No correlation was found between the timing of surgery, mortality, steroid dosage and wound complication. PMID- 1295430 TI - Echocardiographic diagnosis of quadricuspid aortic valve. AB - Isolated quadricuspid aortic valve is a rare congenital anomaly. We present a case diagnosed on cross-sectional echocardiography. To the best of our knowledge, this is the first case report on echocardiographically diagnosed quadricuspid aortic valve in Singapore. PMID- 1295429 TI - Hepatotoxicity of amiodarone. AB - Amiodarone, a commonly used antiarrhythmic agent, has numerous adverse effects. The purpose of this case report is to highlight its hepatotoxicity, an unusual complication of long term amiodarone therapy. Our patient is a 76-year-old man with underlying ischaemic heart disease and recurrent ventricular tachycardia. Eleven months after commencing amiodarone, he developed asymptomatic raised aminotransferases which resolved following drug withdrawal. Amiodarone was then reintroduced and four years later, the patient developed hepatomegaly, worsening liver biochemistry and histopathological changes consistent with early cirrhosis. His symptoms improved following discontinuation of amiodarone. However, hepatomegaly and a low serum albumin still persist four years later. PMID- 1295431 TI - [Contribution of intra-operative measurement of intact parathormone in surgery for primary hyperparathyroidism]. AB - Using a sensitive two-site immunoradiometric assay which detects intact parathormone (iPTH), we studied the decrease in peripheric and jugular plasmatic iPTH during surgical removal of abnormal parathyroid (s). In the next future, results of intact parathormone (iPTH) assay will be given in 45 minutes. In a prospective study of 33 patients operated on for hyperparathyroidism or for cold thyroid nodule, the serum levels of intact PTH was measured intraoperatively in peripheric and in jugular blood. The preoperative mean serum iPTH concentration was 119.23 +/- 172.48 pg/ml and fell to 34.5 +/- 32.21 pg/ml after surgery in 14 cases of primary hyperparathyroidism (p < 0.001). Thirteen out of 14 patients had serum iPTH values less than 65 pg/ml within 15 minutes after parathyroidectomy. The preoperative mean serum iPTH concentration in the 5 secondary hyperparathyroidism was 781.2 +/- 403.19 pg/ml. This value fell to 124 +/- 66.91 pg/ml after parathyroidectomy (p < 0.04). No significant decrease was observed in the mean serum concentration of the 14 patients operated on for cold thyroid nodule. Patients suffering from single parathyroid adenoma presented a significant gradient in jugular plasmatic PTH concentration between the adenoma side and the contralateral one. This gradient decreased during effective parathyroid adenomectomy (309.7 +/- 313.3 pg/ml to 3.7 +/- 35.1 pg/ml). Intraoperative serum iPTH concentration will provide a valuable tool to appreciate the effectiveness of surgical removal of parathyroid glands and to detect the location of parathyroid adenoma when the surgical research is negative. PMID- 1295432 TI - [Epidemiology of goiter in Auvergne]. AB - An epidemiological study about goiter, related to the French national survey concerning school children aged 10-16, was carried out in region Auvergne. The prevalence of goiter was 12.52%, including 2.8% patients with WHO stages I and II, thus being slightly below national average (16.7%). Iodine urinary excretion was 62.9 +/- 34.3 micrograms per gram creatinine (French mean value 85.0), although sometimes major variation was noted in the same area. Later, two studies were performed in adults, in two places of Haute-Loire and Puy-de-Dome, respectively Arsac-en-Velay and Besse-en-Chandesse. Both places were selected because of high frequency of goiter in children. Prevalence in adults was 16.1% in Arsac-en-Velay including 12.5% stages I and II, and 8.9% in Besse-en-Chandesse including 5.9% stages I and II. Mean iodine urinary excretion was respectively 59.78 micrograms/gram creatinine and 43.45 micrograms/liter. Thus, these surveys confirm a significant prevalence of goiter in Region Auvergne, with endemic places, and a generally low iodine urinary excretion. PMID- 1295433 TI - [Partial 3-beta-hydroxysteroid dehydrogenase deficiencies]. AB - An overview of the partial 3 beta-hydroxysteroid dehydrogenase deficiency is presented. The classical, congenital or early postnatal form is characterized by a salt-losing syndrome and/or ambiguous genitalia. The late-onset forms, only recognized for the last ten years and diagnosed with an increasing frequency, are to be systematically suspected in the presence of clinical hyperandrogenism with or without oligomenorrhea. This deficit, involved in both adrenal and gonadal tissues, seems to be transmitted by an autosomal recessive gene. An ovarian 3 beta-hydroxysteroid dehydrogenase deficit can be a primary cause of some cases of polycystic ovary syndrome and the relations with this affection are disputed. The increased ratios of delta 5 steroids/delta 4 steroids ensure the diagnostic conviction while the elevated ratio of 17-hydroxy-pregnenolone/17 hydroxyprogesterone and the normal ratio of 11-desoxycortisol/cortisol allow to eliminate the possibility of a 21-hydroxylase or 11 beta-hydroxylase deficiency, respectively. The treatment is based above all on the glucocorticoid utilization, which can lead to the return of menses and the ovulatory function, but the cutaneous symptoms of hyperandrogenism will be better controlled by cyproterone acetate out of situations of stress. PMID- 1295434 TI - [Genetic susceptibility of insulin-dependent diabetes]. AB - Type I Insulin-Dependent Diabetes Mellitus (IDDM) is an autoimmune disease characterised by the destruction of pancreatic Beta cells. There is an evidence for a contribution of genetic factors to the development of the disease and it is widely documented that HLA antigens contribute to the disease susceptibility. HLA DR3 and HLA-DR4 associations have been firstly described in Caucasian. Recent studies at the gene level have elucidated this HLA association more precisely, pointing out the prominent role of HLA-DQ locus genes. The hypothesis has been proposed that some critical amino-acid at position 57 of DQ Beta chain and at position 52 of DQ Alpha chain both contribute to disease susceptibility. According to the functional role of HLA class II molecules, these particular residues may affect the antigen binding and T cell recognition and therefore contribute to the triggering of the pathological auto-immune response. PMID- 1295435 TI - [Immunologic mechanisms implicated in autoimmune destruction of beta cells in type I diabetes]. AB - Lymphocytic infiltration of the islets of Langerhans results from activation of immunity effector cells during the period preceding clinical onset of diabetes. After escape from thymic selection, the autoreactive cell clones proliferate in the peripheral hemopoietic organs prior to invading the islets of Langerhans. The selection, expansion and activation of autoreactive cells are under genetic control. The development of quantitative tests of cellular immunity should allow determination of the importance of the anti-islet immunologic reaction, suspected at present from the presence of specific autoantibodies in genetically predisposed subjects at high risk of insulin dependence. PMID- 1295436 TI - [Risk markers of insulin-dependent diabetes in the normal population]. AB - Risk factors for IDD have been studied in relatives of patients, in whom the risk is far higher than in the children from the background population. Several factors have been identified as the genetic background at the HLA level (DR and DQ regions) and autoantibodies like islet cells antibodies (ICA) and insulin autoantibodies (IAA). 8,363 sera from schoolchildren (age 6-17 yr) have been tested for the presence of ICA. 150 sera (1.8%) were found positive; the prevalence rate of high ICA titres (> or = 20 uJDF) was very low: 0.2%. ICA titres remained stable over a 8 mth follow-up period. IAA have been measured on the first 2,000 sera and the prevalence rate was 1.2%. Only 3 sera were found positive for the two antibodies, one coming from a diabetic girl. The distribution of the susceptibility alleles at the DQ-HLA region was similar among the ICA-positive and ICA-negative children. PMID- 1295437 TI - [Metabolic markers of type I prediabetes]. AB - Studies of the early metabolic alterations of type 1 diabetes aim at the quantification of the residual beta cell mass and its rate of destruction, as well as identifying predictive markers of insulin dependency. The first phase of insulin secretion during the intravenous glucose tolerance test has been mostly investigated. The test is satisfactorily reproducible provided it is standardized. The age and the insulin sensitivity of the subject should be taken into account when interpreting the results. Moreover, functional phenomenon that may be reversible may take part in the observed alterations of insulin secretion. The abolition of the first phase of insulin secretion always precedes insulin dependency, and has a good positive predictive value in subjects with anti-islet cell antibodies. However, some pre-diabetic subjects already have a low first phase insulin response from the first examination, which does not favour the hypothesis of a linear beta cell destruction and points to the heterogeneity of this stage of the disease. Conversely, profound metabolic alterations have been described with no progression towards insulin dependency, suggesting remission of the autoimmune process. The predictive value of the alterations of insulin secretion using other stimulus will be assessed by ongoing studies. PMID- 1295438 TI - [Screening of type I diabetes in patients' families]. AB - Insulin dependent or type 1 diabetes is an autoimmune disease with a strong genetic susceptibility linked to MHC and non MHC genes. Risk of the disease is 20 fold higher in first degree relatives of patients than in the general population. beta-cell destruction is progressive and marked by the appearance of antibodies to several islet constituents including insulin and glutamate decarboxylase. These markers allow disease prediction specially in children where a population with a 5 years risk approaching 100% can be defined. The intravenous glucose tolerance test can detect a progressive decline of the first phase of insulin secretion, preceding glucose intolerance and hyperglycemia. These screening programs will allow clinical trials currently limited to non specific immuno suppressive agents such as cyclosporine in patients with preclinical diabetes. In the future, identification of targets and effector mechanisms of auto-immune destruction of the beta-cells will allow the evaluation of more specific approaches at earlier stages of the disease. PMID- 1295439 TI - [Immunology of insulin-dependent diabetes. Towards practical applications]. PMID- 1295440 TI - The effect of anti-CD3 on the induction of non-MHC restricted cytolytic activity. AB - The effects of an anti-CD3 mAb on induction of non-MHC restricted cytolysis was investigated. Peripheral blood mononuclear cells (PBMC) from normal donors (29) and cancer patients (18) were cultured in 100 U/ml of interleukin-2 (rIL-2) with and without anti-CD3 mAb (OKT3, 10 ng/ml) for the first 48 hours of incubation. Thereafter, both PBMC cultures were maintained on rIL-2 up to 20 days. PBMC proliferation was enhanced 17-fold in number by day 20 when anti-CD3 mAb and rIL 2 was present during the first 48 hours but only 3-fold by day 20 when rIL-2 alone was present. Concomitantly anti-CD3 mAb but not Lym-1, an isotype matched control, inhibited the induction of lytic activity against both NK sensitive (K562) and NK resistant (Raji) target cell lines. Thus the inhibitory effect is dependent on anti-CD3 mAb stimulating the CD3/TCR T-cell receptor complex. While lytic activity was dependent on the concentration of rIL-2, inhibition of the induction phase of non-MHC restricted lytic activity was independent of the concentration of rIL-2. Flow cytometry analysis indicated that treatment with the anti-CD3 mAb increased the percentage of CD3 positive cells, CD4 positive cells and especially CD25 positive cells, but decreased th percentage of CD56 positive cells. Supernatants from anti-CD3 mAb stimulated cultures also inhibited the induction of non-MHC restricted lytic activity. Lymphokine analysis showed that supernatants of anti-CD3 mAb stimulated cultures had higher levels of TNF-alpha and IFN-gamma. However, TNF-alpha and IFN-gamma alone or in combination could not mediate the inhibitory effect. The inhibitory factor(s) was partially purified by sequential chromatography on matrices of controlled pore glass and Sepharose CL 6B. The molecular weight of the inhibitory factor(s) was less than 67K. These studies have identified a novel regulatory pathway controlling non-MHC restricted cytolysis. Perturbation of the T-cell CD3/TCR complex with the anti-CD3 mAb results in the secretion of a soluble mediator that down-regulates the induction of rIL-2 dependent non-MHC restricted cytolysis. PMID- 1295441 TI - Monoclonal antibody SP-21 defines a sialosyl-Tn antigen expressed on carcinomas and K562 erythroleukemia cells. AB - Monoclonal antibody (mab) SP-21 resembles the well established mab B72.3 by high affinity binding to peptide linked sialosyl-Tn disaccharide, NeuAc alpha 2-6 GalNAc alpha, and non-reactivity to the related trisaccharide NeuAc alpha 2-6 (Gal beta 1-3)GalNAc alpha. Although mab SP-21 may be classified, accordingly, into the family of mabs defining the sialosyl-Tn antigen, its fine specificity is distinct from the reference antibody B72.3 by binding of mab SP-21 to fetal mucins from human meconium or amniotic fluid. The distinct immunoreactivity of this mab is also documented by its specific cell staining of the erythroleukemia cell line K562, where it binds to a 105 KDa glycoprotein. Moreover a subpopulation of normal lymphocytes stains to this mab SP-21. PMID- 1295442 TI - Anticancer activities of orally administered menogaril against human stomach and breast cancers implanted in nude mice. AB - The therapeutic effects of orally administered menogaril, a semisynthetic analog of the anthracycline antibiotic nogalamycin, were studied on a panel of human stomach and breast cancer xenografts. The maximum tolerated dose (200 mg/kg) of menogaril was administered 3 times every 4 days and its growth-inhibitory effects on subcutaneously implanted tumors in nude mice were evaluated. Menogaril significantly retarded the growth of 3 out of 7 stomach cancers, SC-2, SC-9 and 4 1ST, and 3 out of 4 breast cancers, H-31, MC-2 and MX-1, with overall response rates of 43 and 75% for stomach and breast cancers, respectively. Some of these relatively responsive cancers were also treated by daily oral administration for 5 consecutive days, but the anticancer effects of the intermittent administration seemed to be better. These results suggest that menogaril may be effective against stomach and breast cancers when orally administered. PMID- 1295444 TI - A randomized, comparative study of combination chemotherapies in advanced gastric cancer: 5-fluorouracil and cisplatin (FP) versus 5-fluorouracil, cisplatin, and 4'-epirubicin (FPEPIR). Kyoto Research Group for Chemotherapy of Gastric Cancer (KRGCGC). AB - Sixty patients with inoperable or recurrent gastric cancers were randomly assigned into 2 treatment regimens: the FP regimen, consisting of cisplatin (CDDP, 50 mg/body, d1) + 5-fluorouracil (5-FU, 250 mg/body, d2-d5), or the FPEPIR regimen, CDDP+5-FU (FP) + 4'-epirubicin (EPIR, 30 mg/m2, d2), administered intravenously every 2 weeks. The objective responses were evaluated in 43 patients (FP: 21; FPEPIR: 22). The response rates were 24% (5PR/21) for FP and 27% (6PR/22) for FPEPIR. Objective responses were seen in 1 primary lesion and 4 metastatic lesions in patients on the FP regimen, and in 3 primary lesions and 4 metastatic lesions in patients on the FPEPIR regimen. The 6 month and 1 year survival rates were 34% and 13% for FP, and 55% and 27% for FPEPIR, respectively (not significant). Significantly higher survival rates were demonstrated in those patients with recurrent cancers (p < 0.01) and those who responded to the FPEPIR regimen (p < 0.05). Drug toxicities were assessed in 56 patients, and were in general mild and well tolerated. However, the FP regimen induced significantly less neutropenia (p < 0.01) and less complete alopecia (p < 0.01) than the did FPEPIR regimen. These results suggest that FPEPIR may be a more beneficial regimen for the treatment of gastric cancer than FP, and may be indicated for further clinical trials. PMID- 1295443 TI - p53 mutation in human nasopharyngeal carcinomas. AB - Nasopharyngeal carcinoma (NPC) is the third most common cancer in the southern provinces of China, but a rare cancer in other parts of the world. Epidemiological studies suggested a multifactorial etiology of NPC involving infection of Epstein Barr virus (EBV), genetic predisposition, environmental factors, such as consumption of salted fish, and other unknown factors. p53 mutation is a common event in many forms of human cancers but its possible involvement in the pathogenesis of NPC has not been examined. The presence of p53 mutation in NPC is studied by the sensitive PCR-SSCP analysis and direct DNA sequencing method. The frequent sites of p53 mutation (exons 4 to 8) reported in other human tumors were studied. Thirty-eight biopsied tumors of NPC and 4 NPC cell lines were examined for the presence of p53 mutation. No mutation of p53 resulting in change in amino acid sequence of the encoded p53 protein was identified in any of the biopsies tumors. RFLP studies of the biopsied materials of NPC also revealed no loss of heterozygosity at chromosome region 17p13 in 15 out of 15 informative cases, which further supports the conclusion that p53 mutation is an infrequent event in NPC. Apparently, p53 mutation has no significant role in the pathogenesis of this special group of human cancers. However, p53 mutation is frequently observed in cell lines derived from the primary NPC tumors. All the three NPC cell lines examined carry a missense p53 mutation, suggesting that mutation of the p53 gene may confer growth advantage to the tumor cells to become established in culture. PMID- 1295445 TI - Laminin and 67 kD laminin binding protein in mouse B16 melanoma cells and 3T3 fibroblast spheroids. AB - Multicellular spheroids which promote cell-cell and cell-matrix interactions were prepared in culture with mouse B16 melanoma cells (pigmented or non pigmented) alone or mixed with mouse 3T3 fibroblasts. Their volume and proliferation or necrosis rate were evaluated. As measured by dot blot immunoassay, laminin was mainly produced by fibroblasts rather than by melanoma cells. High levels of laminin B1 chain mRNA were detected only in spheroids composed of 3T3 fibroblasts. The levels of 67 kD laminin binding protein mRNA were high in all cell populations studied here. PMID- 1295446 TI - A prospective study of tissue polypeptide specific antigen (TPS) in breast cancer diagnosis. AB - The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in sera from patients with breast cancer and patients with benign breast disease. The results for TPS were compared with those for TAG 12, CA 15-3 and MCA. The cutoff levels (90% specificity) determined for each test were 108.0 U/1 for TPS, 57.5 KU/1 for TAG 12, 24.8 KU/1 for CA 15-3 and 9.7 KU/1 for MCA. The diagnostic sensitivity of the TPS test was 0.21, for the TAG 12 test it was 0.2, 0.13 for the CA 15-3 test and 0.12 for the MCA test in detecting breast cancer. TPS, TAG 12, CA 15-3 and MCA tests were tested in a multivariate analysis to find the best combination of independent predictors of breast cancer. The most important predictor of breast cancer was TAG 12 followed by TPS. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The diagnostic score (DS) was: DS = TPS x 0.0085 x TAG 12 x 0.0596 - CA 15-3 x 0.0866 - MCA x 0.2938 + 0.1738. The sensitivity of the DS in detecting breast cancer was 55% with a specificity of 90% and an efficiency of 64%. In conclusion, new tumour markers TPS and TAG 12 may have some value in breast cancer diagnosis. In particular, the results indicate the usefulness of computer assistance and a simple diagnostic score when tumour markers are used in breast cancer diagnosis. PMID- 1295447 TI - The cytoskeleton as a subcellular target of the antineoplastic drug lonidamine. AB - Lonidamine (LND), a dichlorinated derivative of indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of normal and neoplastic cells. A target effect of the drug on the cell membrane structure was hypothesized. Thus, in order to elucidate better the mechanism of action of LND, the drug effects on the cell surface as well as on main cytoskeletal elements, i.e. actin microfilaments, microtubules and intermediate filaments, were investigated. In particular, an immunocytochemical and ultrastructural study was performed using two different cell lines: epithelial squamous carcinoma (A431) and melanoma (M14) cells. Treatment with 0.8 mM LND for 8 hr induced a remarkable rearrangement of the F-actin molecules with the disappearance of the stress fibers. As far as microtubules are concerned, formation of perinuclear patches of tubulin were detected after LND treatment. Intermediate filaments appeared to be differently affected by LND in the two cell types. Such changes were detected as an early phenomenon and the extent of the effects observed was positively related to the cell surface alterations and to the loss of cell viability, suggesting that the cytoskeletal elements might represent an additional target in the mechanisms of cytotoxic action of LND. PMID- 1295448 TI - Cell transforming and oncogenic activity of 2,3,7,8--tetrachloro--and 2,3,7,8 tetrabromodibenzo-p-dioxin. AB - We have developed a host-mediated assay system for detection of the transforming activity of chemical carcinogens on peritoneal macrophages, directly, as well as indirectly acting carcinogenic substances administered intraperitoneally to NMRI mice could be examined in this way. Resident macrophages were recovered by peritoneal lavage from treated and untreated mice and cultured in soft agar. After 5-6 days normal and transformed cells could be distinguished. Statistical analysis comparing cells from 2, 3, 7, 8-tetrachlorodibenzo-dioxin (TCDD)-treated animals with those from control mice proved that the test is positive at least on a significance level of 5%, using the t-test. TCDD revealed a cell-transforming potential that showed a dose-dependent response in this host-mediated assay. The co-carcinogenic activity of TCDD was established in experiments with diphenylhydantoin. Low doses of diphenylhydantoin which did not exhibit any transforming potential in our system gained a high oncogenic potential by the simultaneous administration of low doses of TCDD, which also had no transforming activity. We have compared the cell transforming potential of TCDD with its bromo analog TBrDD. The cell transforming potential of TCDD is 7 times that of TBrDD. We have succeeded in establishing a permanent cell lined from mice treated with TBrDD. The oncogenicity of this cell line was tested in athymic nu/nu mice. Animals treated subcutaneously with these cells (1 x 10(6) cells) developed tumors at the injection site. Using monospecific antibodies to tumor necrosis factor alpha (TNF-alpha), we have found that TCDD stimulates the secretion of TNF alpha. The experimental data reported here lead to the conclusion that TCDD has a carcinogenic as well as a co-carcinogenic activity and has the property to induce TNF-alpha. PMID- 1295449 TI - Effect of natural beta-interferon on estrogen receptor mRNA of breast cancer cells. AB - We have demonstrated that natural beta-interferon (beta-IFN) enhances estrogen receptor (ER) mRNA of a human breast cancer cell line, CG-5. Cells were sensitive to the effect of beta-IFN at concentrations ranging from 10 to 100 IU/ml. The increase of ER mRNA was seen after 48 hr of treatment in at least three separate experiments. Our results are in agreement with the previously observed enhancement of receptor protein. In addition, they suggest that the IFN-induced promotion of the antiproliferative activity of drugs which act via ER may be due, in part, to increased receptor synthesis. PMID- 1295450 TI - Transcriptional activation of the human immunodeficiency virus long terminal repeat sequences by tumor necrosis factor. AB - The recombinant plasmid pBHIV-1 carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1), linked to the reported chloramphenicol acetyl transferase (CAT) gene, was introduced into human and rat fibroblasts. Stable transfectants were obtained which were resistant to genetecin and expressed CAT-activity from the HIV-1 LTR. The response to TNF alpha was studied. It was found that, at the optimum concentration of 100 IU/ml in human and 1000 IU/ml in rat fibroblasts, the expression of CAT was stimulated by 2.1 and 2.5 fold respectively. Our findings suggest that TNF-alpha in physiological concentrations can transcriptionally activate the HIV-1 LTR sequences and this may play an important role in the pathogenesis of HIV infection. PMID- 1295451 TI - Growth inhibition of anaplastic glioma cells by nerve growth factor. AB - Nerve growth factor (NGF) inhibited cellular DNA synthesis of rat T9 anaplastic glioma cells in a dose-dependent manner in the range of 0.5-5 micrograms/ml. Oxidation of 2 to 3 tryptophan residues of NGF, which had been known to destroy biological and immunological activity, greatly diminished its inhibitory effect on DNA synthesis. The inhibition was also abolished by anti-NGF IgG. Flow cytometric analyses and immunocytochemical assays of DNA synthesis using bromodeoxyuridine incorporation at various times during cell exposure to NGF revealed that the growth inhibition was attributable to gradual accumulation of growth-arrested cells at the G1 phase. Synthesis of nuclear regulatory proteins JUN and p53 was inhibited preferentially and progressively by NGF as inhibition of DNA synthesis increased. PMID- 1295452 TI - Mode of EGF action on cell cycle kinetics in human breast cancer cell line MCF-7: some evidence that EGF acts as a "progression factor". AB - EGF is known to play a very important role in the growth regulation of tumor cells. We have determined the effect of EGF in the absence and in the presence of serum on the cell cycle of MCF-7 cells synchronized in the G1 phase by serum deprivation. In the presence of 1% serum, EGF was found to increase DNA synthesis to 120% of control (P < 0.02), but did not modify the transition time from G1 into S phases, nor the cell doubling time during the first generation following the cell synchronization. The autoradiography analysis of 3H-thymidine labeled cells indicated that, following 24 h of EGF treatment, a constant additional number of cells (11 +/- 1.5%, P < 0.002) were recruited into the S phase in the presence as well as in the absence of serum. These data indicate that EGF exerts its mitogenic effect on MCF-7 cells by increasing the percent of S phase cells without modulating the cell doubling time. However, in the absence of serum a significant increase of thymidine incorporation in whole cells required 12 h of EGF treatment, whereas a 6 h-incubation with EGF was sufficient to stimulate DNA synthesis when synchronized cells were pretreated with serum for 6 h, suggesting that EGF sensitivity is dependent on the cell advance into the G1 phase at the moment of EGF addition. Topographical analysis of 3H-thymidine-labeled cells aimed at determining the spatial distribution of cells in culture revealed that EGF-stimulated cells were disposed near proliferative cells, indicating the local influence on cell proliferation. Taken together, our results suggest that in the MCF-7 cell line, EGF acts in the G1 phase by increasing the proportion of S cells without affecting the duration of the cell cycle. In our model, EGF seems to act as a "progression factor", in that it stimulates only cells already traversing a certain stage in the G1 phase under the action of serum factors, cell secreted diffusible products and cell-cell contact. PMID- 1295453 TI - PSK (krestin) potentiates chemotherapeutic effects of tamoxifen on rat mammary carcinomas. AB - A total of 20 mg of 7,12-dimethylbenz[a]anthracene (DMBA) was administered orally to 41 female Sprague-Dawley (SD) rats (control group), and 60 mg/kg of Krestin (PSK) were orally administered daily to 38 rats (PSK group) after DMBA administration. The average development period (9.6 weeks) of DMBA-induced tumors in the PSK group was significantly longer (P < 0.02) than that (7.9 weeks) in the control group. Average estrogen receptor (ER) levels of established tumors were almost the same between these two groups. However, the chemotherapeutic effect of tamoxifen (TAM) was significantly enhanced by PSK pretreatment. PMID- 1295454 TI - Relationship between resonance energy and carcinogenic activity of benz[c]acridines. AB - In order to investigate the correlation between the carcinogenic activity of benz[c]acridines and the electron density, the Huckel orbital method was used. Resonance energies, circuit resonance energies and bond currents of benz[c]acridines were calculated by Aihara's TRE theory. It was shown that these compounds had very stable aromatic characters with positive resonance energies and that the resonance energies per pi-electron values for the compounds with lack of the double bond corresponding to the K-region from the parent skeleton were more stable than those of their parent compounds. 7-Methyl-benz[c]acridine derivatives with the methyl groups at 7-, 7, 9-, 7, 10-, 7, 11-, 7, 9, 10-, or 7, 9, 11-positions except 5, 7-dimethylbenz[c]acridine had potent carcinogenic activity and significantly lower resonance energy per pi-electron. PMID- 1295455 TI - Cytostatic effects of various alkyl phospholipid analogues on different cells in vitro. AB - Phospholipid analogues were studied with regard to their cytostatic activity on different tumour cell lines and on murine bone marrow cells. Compounds compared for their activity were alkylglycero- and alkyl-phosphocholines with the corresponding serines and the alkylphosphocholines and -serines with the corresponding phosphono derivatives. Moreover, compounds containing cytidine 5' diphosphate instead of the phospho (or phosphono-) choline or serine moiety were studied. rac-2-Chloro-2-deoxy-2-deoxy-1-0-hexadecyl-glycero-3-phosphocholine (cpd. Id), hexadecylphosphocholine (cpd. Ia) as well as hexadecylphosphonocholine (cpd. Ib) inhibited growth of tumour cells in suspension and monolayer culture and their colony and cluster formation in agar culture but not that of bone marrow cells. The exchange of choline for serine in these compounds results in the loss of this type of antitumour specificity. However, dodecylphospho-L-serine (cpd. IIc) is as specific as the choline derivatives Ia, b, d mentioned. Thus, for serine compounds the specificity for tumour cells might depend in a critical way on the length of the alkyl chain. The phosphono compounds Ib, IIb show almost the same activity as the corresponding compounds hexadecylphosphocholine (cpd. Ia) or hexadecylphosphoserine (cpd. IIa). The CDP-derivatives (IIIa, d, e, f) inhibited growth of tumour cells in suspension or monolayer cultures but not the colony and cluster formation in agar (i.e. they do not decrease the plating efficiency) from either tumour or bone marrow cells. PMID- 1295457 TI - Transforming growth factor-beta is not the major soluble immunosuppressor in the microenvironments of human breast tumours. AB - The immunosuppressive nature of the human breast cancer microenvironment was investigated. The soluble fraction of individual tumours was tested for its ability to influence the activation of peripheral blood lymphocytes (PBL) by interleukin-2 (IL-2) and to effect the continued proliferation of cells which had been pre-activated with IL-2. In all cases, both assays were profoundly inhibited (90-100%). None of this inhibition was due to cell killing by the tumour-derived soluble material (TDS). Sixty-two percent of TDS tested contained measurable transforming-growth factor-beta (TGF-beta) activity; following acidification TGF beta was present in all TDS. However, in neither case was this material present in sufficient amounts to account for the degree of inhibition observed. In addition, neutralisation experiments failed to demonstrate consistent relief of inhibition in the presence of excess anti-TGF-beta antisera. These results demonstrate that TGF-beta s are not the major soluble immunosuppressive materials within human breast tumours. PMID- 1295456 TI - Receptors for estrogen and progesterone in breast carcinoma in situ. AB - In contrast to the situation in invasive breast carcinoma, there are only few reports on the levels of receptors for estrogen (ER) and progesterone (PgR) in pre-invasive (in situ) breast carcinoma. In the present study ER and PgR levels were analyzed in 57 in situ human mammary carcinomas using a quantitative enzyme immunoassay method. Intraductal carcinoma was the dominating histopathological subgroup (75%). Within this subgroup the non-comedo and comedo variants comprised 66 and 34 percent respectively. Intralobular and papillary in situ subtypes were the second most frequent subgroups, representing 11% each. Using a cut-off level of 0.05 fmole/microgram DNA to define receptor poor and rich tumors we found that thirty-one out of the 57 cases (54%) were ER-rich. In the ER-rich tumors the receptor levels varied between 0.05 and 6.50 fmole/microgram with a mean concentration of 0.80 fmole/microgram DNA. Fifteen of 51 (30%) tumors were classified as PgR-rich tumors in which the levels ranged between 0.05 and 2.90 fmoles/microgram DNA, with a mean concentration of 0.45 fmoles/microgram DNA. Two thirds of the non-comedo, lobular and papillary variant were ER rich. A majority (80%) of comedo tumors were ER poor. Our findings show that 54% of in situ breast carcinomas have the molecular prerequisites for response to antiestrogen therapy which is of interest when planning adjuvant treatment protocols. PMID- 1295458 TI - Tumour levels of O6-alkylguanine-DNA-alkyltransferase and sensitivity to BCNU of human xenografts. AB - Tumour levels of O6-alkylguanine-DNA-alkyltransferase (O6 AT) and glutathione content (GSH) were correlated with 1, 3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) sensitivity in two human ovarian cancer xenografts (HOC8 and HOC18) and in two human glioblastoma xenografts (HG12 and HG15). HOC8 and HOC18, which were not responsive to BCNU treatment, showed O6 AT levels 14 and 23-fold higher than HG12 that was moderately sensitive to the same BCNU treatment. HG15, which was more sensitive to BCNU than HG12, showed significantly lower O6 AT levels. GSH levels were similar in all tumor xenografts. These data further stress the importance of O6 AT level as a relevant parameter for nitrosourea response in human tumours. PMID- 1295459 TI - Demonstration of monoclonal anti-carcinoembryonic antigen (CEA) antibody internalization by electron microscopy, western blotting and radioimmunoassay. AB - One of the important factors affecting the action of monoclonal antibodies (Mabs) or immunoconjugates on tumour sites depends on whether the Mab is internalized by the cancer cells in question. The underexplored subject of internalization is discussed in this paper, and a number of in vitro techniques for investigating internalization are evaluated, using a model which consists of a well characterized anti-carcinoembryonic antigen (anti-CEA) Mab and a number of CEA expressing human cancer cell lines. Employing two alternative radiolabeling assays, evidence for internalization of the anti-CEA Mab by a CEA-positive colorectal cancer cell line (LS174T) was obtained throughout the time intervals examined (5 min to 150 min). Electronmicroscopy employing horseradish-peroxidase labeled anti-CEA Mab and control antibody permitted direct visualization of anti CEA Mab-related staining in intracellular compartments of a high CEA-expressor human colorectal cell line (SKCO1). Finally Western blots of samples derived from cytosolic and membrane components of solubilized cells from lung and colonic cancer cell lines provided evidence for internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 minutes. Internalized anti-CEA was detected in all CEA expressing cell lines (LS174T, SKCO1, BENN) but not in the case of a very low CEA expressor line (COLO 320). PMID- 1295460 TI - Differential stimulatory and inhibitory responses of human MCF-7 breast cancer cells to linoleic acid and conjugated linoleic acid in culture. AB - Consumption of dietary fat has been linked to the high incidence of certain cancers. However, recent research has stimulated interest in conjugated linoleic acid (CLA), a newly recognized anticarcinogenic fatty acid. Human MCF-7 breast cancer cells were incubated for 12 d in culture medium supplemented with various concentrations (1.78-7.14 x 10(-5) M) of linoleic acid (LA) or CLA. Linoleic acid initially stimulated MCF-7 cell growth with an optimal effect at concentrations of 3.57-7.14 x 10(-5) M, but was inhibitory at similar concentrations after 8 and 12 d of incubation. In contrast, CLA was inhibitory to cancer cell growth at all concentrations and times tested. Cell growth inhibition by CLA was dose- and time dependent. Growth retardation at the prescribed LA and CLA concentrations ranged, respectively, from 4 to 33% and 54 to 100% following 8 to 12 d of treatment. At similar LA and CLA concentrations, cytostatic and cytotoxic effects of CLA were more pronounced (8-81%) than LA. These in vitro results suggest that CLA is cytotoxic to MCF-7 cells. PMID- 1295461 TI - A simple fluorescent technique for screening cervical cells prior to nuclear analysis. AB - Monolayer spreads of cervical cells were prepared and stained with haematoxylin and rhodamine-alpha-N-agmatine, a fluorescent marker for a cell surface protease. Mature epithelial cells from normal cervices lacked this cell surface enzyme and did not fluoresce. The abnormal cells possessed the cell surface enzyme, bound the probe and were quickly detected by fluorescence microscopy. The degree of abnormality of these fluorescent cells was determined by examination of their nuclear details, with the result that mild, moderate and severe dyskaryotic cells could be defined. PMID- 1295462 TI - Immunoscintigraphic detection of primary and metastatic spontaneous canine osteosarcoma with F(ab')2 fragments of osteosarcoma-associated monoclonal antibody TP-1. AB - Monoclonal antibody TP-1 has been shown to bind selectively to human and canine osteosarcoma cells in vitro using immunohistochemical stains. This report describes the in vivo administration of radioiodinated F(ab')2 fragments of monoclonal antibody TP-1 in dogs with primary and/or metastatic spontaneous osteosarcoma. Two dogs were injected with 131labeled F(ab')2 TP-1 and two dogs were injected with 123labeled antibody fragments. Immunoscintigraphy successfully demonstrated the radiolabeled antibody fragments in 6/6 known primary or metastatic lesions and in addition detected 4 metastatic lesions not diagnosed by conventional radiographs. Concurrent imaging of 99mTc labeled autologous erythrocytes in two dogs confirmed that the accumulation of radiolabeled antibody fragments was independent of the blood pool. There was no immunoscintigraphic evidence of localization of radioiodine to normal organs or tissues other than those expected to accumulate free iodine. The present study has demonstrated the potential of monoclonal antibody TP-1 F(ab')2 fragments for early detection of metastatic spread of spontaneous osteosarcoma. PMID- 1295463 TI - Further evidence for different isoenzymic forms of a cell surface protease, guanidinobenzoatase, associated with tumours. AB - Normal colonic epithelial cells possess a cell surface protease referred to as guanidinobenzoatase (GB) and a corresponding cytoplasmic protein inhibitor of GB. Colonic carcinoma cells possess two isoenzymic forms of GB, the normal and the carcinoma specific form, each of which is recognised by the corresponding inhibitors present in the cytoplasm of colonic carcinoma cells. An affinity purified inhibitor preparation obtained from the cytoplasm of cultured colonic carcinoma cells inhibited these two colonic carcinoma isoenzymic forms of GB but not the GB associated with other forms of tumour. The data suggest that each cell type possessing isoenzymic forms of cell surface GB also possesses the corresponding cell-specific inhibitors of GB. PMID- 1295464 TI - Sequence-dependent activity of 5-fluorouracil plus tauromustine in a transplantable well-differentiated murine colon adenocarcinoma. AB - Previous in vitro studies with 5-Fluorouracil (5-FU) plus Tauromustine (TCNU) demonstrated sequence-dependent effects. This study extended these investigations into an in vivo experimental model, relevant to clinical disease. A transplantable murine adenocarcinoma of the colon, MAC 29, was shown to have stable histology and reproducible growth. This model was used to determine the influence of sequence of administration of this drug combination. Effects ranged from antagonism, with 5-FU given 24 hours before TCNU, to addition, simultaneous treatment, and synergism, 5-FU 24 hours after TCNU. Careful consideration of sequence should be made during the evaluation of this combination in clinical trials. PMID- 1295466 TI - Suppressive activity of acivicin on murine bone marrow hemopoietic progenitors. AB - Acivicin (AVC), a L-glutamine antagonist, is an intriguing antimetabolite coupling cell growth inhibition activity with differentiating effects. In this in vivo study the influence of acivicin on mice bone marrow hemopoietic progenitors was tested. 10 mg/kg b.w./day of acivicin were i.p. injected in B6D2F1 mice for nine days. Leucocyte and reticulocyte level (in peripheral blood), CFU-S (multipotent stem cells) and GM-CFU (granulocyte-macrophage committed progenitors) content in bone marrow were determined during drug administration and for 14 days thereafter. All tested populations decreased severely during the first days of treatment. The drop was particularly striking for bone marrow CFU S. The recovery of hemopoietic progenitors, however, began while AVC was still administered. These results suggest that the effects of acivicin on normal mouse hemopoietic system are mainly inhibitory, causing considerable myelosuppression. PMID- 1295465 TI - The expression of the ras p21 oncoprotein in the bone marrow smears of children with acute leukemia. AB - Point mutations of the ras genes have been detected in various hematologic malignancies. This genetic event may either occur in all malignant cells or be acquired by different subclones, which however, cannot be demonstrated adequately by analyzing only DNA derived from patient specimens. The availability of the ras p21 monoclonal antibody (MoAb) Y 13259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. In this report the expression of the ras p21 oncoprotein in the bone marrow smears of 35 children with acute leukemia has been analyzed. The smears were treated with the MoAb Y 13259, biotinylated goat anti-rat IgG, streptavidin, peroxidase and stained with diaminobenzidine (DAB). The intensity of the staining was evaluated by two independent observers as negative or equivocal (-/+), moderate (+) or intense (++), by counting one thousand cells. Patients were also classified according to the percentage of the stained cells into four groups (0, I, II, III). It was found that 22/35 (63%) were (+) or (++) positive as follows: 11/21 (52%) with ALL CALLA (+), 2/2 ALL-B, 3/3 ALL-T and 6/9 AML. In Group 0 (none of the blasts was stained) were 13/35 (37%), as well as in Group I (1 to 25% of the blasts stained 1+ or 2+ positive), while in Group II (26 to 50% positive stained) 3/35 and in Group III (more than 51% stained) 6/35, all of which were AML (6/9). It is concluded that the immunohistochemical analysis of the ras p21 in blast cells of children with acute leukemia may demonstrate that ras gene expression in some subclones, the intensity and percentage of which may be of some clinical importance. PMID- 1295467 TI - Intracellular accumulation of free calcium in mouse tumor cells exposed to anticancer drugs. AB - Alterations in concentrations of intracellular free calcium ([Ca2+]i) were examined in mouse sarcoma S-180 cells exposed to cisplatin, mitomycin C and adriamycin, as related to cell viability. The [Ca2+]i was measured using the fluorescent Ca2+ indicator, fura-2. During the first 24 hr of incubation of the cells in vitro, in the presence of the drugs, the [Ca2+]i was lower than in the control cells. After 24 hr of incubation, the [Ca2+]i began to increase at a time when the cell viability was reduced to 50% of the controls, and finally exceeded 1 microM with reduction to 10%. The increase in [Ca2+]i was reciprocal to the loss of the cell viability. Changes in Ca2+ concentrations in the medium did not alter the results. These findings suggest that in the presence of anticancer drugs there is an accumulation of free Ca2+ with a release of this ion from internal stores and that cell death follows disruption in the homeostasis of intracellular Ca2+. PMID- 1295469 TI - Antitumor activity of orally administered SMANCS, a polymer-conjugated protein drug, in mice bearing various murine tumors. AB - The antitumor activity of an oily formulation of SMANCS (oily SMANCS), which is a product of conjugation between a proteinaceous antitumor antibiotic neocarzinostatin and poly (styrene-co-maleic acid), after oral administration to mice inoculated with various murine tumors was investigated. BALB/c mice, inoculated either s.c. or i.p. with allogeneic (sarcoma-180) or syngeneic (RL male 1 leukemia and Meth A fibrosarcoma) tumors, were treated with oily SMANCS orally or with an aqueous formulation of SMANCS (aqueous SMANCS) i.v. or i.p. Oral administrations of oily SMANCS or i.v. administrations of aqueous SMANCS to mice bearing three types of tumors in the ascites form resulted in a weak inhibition of tumor growth as compared to the complete inhibition of these tumors by aqueous SMANCS administered i.p. In mice bearing solid tumors, tumor growth was inhibited by 63-82% when a 10 mg/kg dose of oily SMANCS was administered orally to these mice. The antitumor potential of oily SMANCS administered orally was comparable to that obtained from solid tumor-bearing mice receiving i.v. doses of aqueous SMANCS. These results suggest that the oral administration of oily SMANCS to mice bearing various solid tumors inhibits the tumor growth as effectively as aqueous SMANCS administered i.v. PMID- 1295468 TI - Flow cytometric DNA measurement in benign and malignant human thyroid tissues. AB - The occurrence of aneuploidy in 108 normal, benign and malignant thyroid tissues was evaluated by DNA flow cytometry. Aneuploid cell populations were found in 60% of the papillary carcinomas, 67% of the follicular carcinomas, 52% of the follicular adenomas and in 10% of the multinodular goiters. None of the non neoplastic thyroid lesions (chronic thyroiditis and Graves' disease) showed aneuploidy. No significant differences in frequency of aneuploidy and DNA index were found between the well-differentiated and trabecular types of the papillary carcinomas (53%; 1.29 +/- 0.10 vs 75%; 1.30 +/- 0.10, respectively), although the latter type of papillary carcinomas have been shown to be associated with a more aggressive clinical behavior. Also no differences in frequency of aneuploidy were noted between the follicular carcinomas and the follicular adenomas, but the DNA index was significantly higher in the former. These findings indicate that flow cytometric analysis of DNA content may not be helpful in the evaluation of the clinical behavior of papillary carcinomas or in the determination of malignancy of follicular tumors, but may be useful in differentiating neoplastic from non neoplastic thyroid lesions. PMID- 1295470 TI - Mutant p53 product in patients with stage III cervical cancer. AB - Mutations in the p53 gene stimulate cell division. In our study we assessed the prognostic value of mutant p53 overexpression in cervical cancer stage FIGO III detected by immunohistochemistry. In 43 tissue specimens were detected p53 overexpression in 20 cases. Mean survival time was 36.4 (SE +/- 7.66) months in the p53 protein positive group. The group without p53 overexpression showed a mean survival time of 28.6 (SE +/- 3.85) months. p53 protein overexpression had no prognostic value in patients with stage III cervical cancer. PMID- 1295471 TI - Total control of chemotherapy induced emesis. AB - A combination of lorazepam, prochlorperazine, dexamethasone, scopolamine and ondansetron was used to prevent and diminish the occurrence of nausea and vomiting during administration of emetogenic chemotherapy. Immediately prior to administering chemotherapy a cutaneous scopolamine patch was applied to the retroaural area, prochlorperazine 5 mg was given orally, and intravenous (IV) lorazepam 0.5 mg, ondansetron 10 mg and dexamethasone 10 mg were given. The last two were repeated after 4 hours twice, and lorazepam at 6 hour intervals for four doses. A chemotherapy course consisted of mitoxantrone 20 mg/m2 i.v., followed by thiotepa 60 mg/m2 followed by 3 grams/m2 of cyclophosphamide as a constant infusion over 48 hours. There were 80 courses given to 30 women and one man with a median age of 42 years (29-58). Complete protection from vomiting in all 80 courses resulted. Minor nausea occurred in 25 courses. The antiemetic regimen was well tolerated and all patients received all the doses as prescribed. PMID- 1295472 TI - Ly-6A/E gene is widely expressed among transformed nonhematopoietic cells. Autocrine modulation by interferon. AB - Expression of the Ly-6A/E gene by transformed cells was investigated in 14 cell cultures of C57BL/6 and BALB/c mouse origin derived from spontaneous or chemically-induced non-hematopoietic tumours and from cells transformed by SV40 virus. Histologic types included carcinomas, sarcomas and a melanoma. Thirteen out of 14 cell cultures expressed membrane Ly-6A/E antigens; only the B16-A melanoma was negative, but it expressed Ly-6A/E after incubation with IFN-gamma. The effect of in vitro permanence was studied on early (< 10) and late (> 20) passages of B16-A melanoma and MN/MCA1 fibrosarcoma. Late passage B16-A cells were Ly-6A/E-negative and refractory to induction of Ly-6A/E (but not of H-2 antigens) by IFN-alpha, IFN-beta, or IFN-gamma; MN/MCA1 maintained a high expression of Ly-6A/E, but no increase was induced by IFNs. It was found that both early and late in vitro passages of MN/MCA1 actively produced IFN alpha/beta. The analysis of cells of fibroblastic origin revealed a significant correlation between IFN release in the culture medium and Ly-6A/E levels. Culture of fibrosarcoma cells in the presence of an anti-IFN-alpha/beta serum reduced Ly 6A/E expression, thus indicating the existence of an autocrine loop. PMID- 1295473 TI - Production of human macrophages with potent antitumor properties (MAK) by culture of monocytes in the presence of GM-CSF and 1,25-dihydroxy vitamin D3. AB - Antitumoral macrophages (MAK) were obtained by the culture of human mononuclear cells in hydrophobic bags. From one cytapheresis, up to 10(9) mature macrophages could be purified by elutriation after one week of culture in IMDM medium in the presence of 2% human AB serum. These MAK cells were used for adoptive treatment in metastatic cancer patient with no dose-limiting toxicity. The present study aimed to improve the average MAK yield by addition of GM-CSF and of dihydroxy cholecalciferol. The differentiated macrophages obtained presented higher antitumoral functionality in response to rh-IFN gamma than in their absence. These MAK presented all the differentiation antigens of cytotoxic macrophages compared to MAK cells differentiated in standard medium. They killed human tumor targets effectively in vitro at a low (1/1) effector/tumor ratio; furthermore, the antitumoral activity reached by MAK cells after IFN gamma activation appeared to be stabilized for several days. PMID- 1295474 TI - Mechanism of action of tricyclic drugs on Escherichia coli and Yersinia enterocolitica plasmid maintenance and replication. AB - Tricyclic medical compounds like many other non-antibiotics exhibit antimicrobial activities. Two chemically representative groups were tested in plasmid DNA transformation and replication to assign intracellular target sites responsible for the multiple effects in Escherichia coli and Yersinia enterocolitica cells. To analyse the mechanism of action at the molecular level, the effects of chlorpromazine, 7,8 dioxochlorpromazine, promethazine, methylene blue, imipramine, cannabidiolic acid and tetrahydrocannabidiolic acid were examined at several points in the course of transformation, in plasmid replication and on the topological state of plasmid DNA. Two possible target sites were identified, one of them involving membrane binding sites which participate in plasmid DNA replication. Drug binding at these sites interfered with the replicating plasmid DNA and membrane protein complex, preventing the proper processing of the replication that resulted in plasmid loss. The other in vivo and in vitro effect was observed on the topological state of plasmid DNA. Tricyclic drugs intefered with energy dependent gyrase activity and promoted the relaxation of plasmid DNA, causing disturbances in gene expression and in plasmid replication. The results give insight into the chemical structures connected with significant specific antimicrobial effects. PMID- 1295476 TI - Synthesis and antitumor activity of a new cis-diammineplatinum (II) complex containing procaine hydrochloride. AB - This paper refers to some of the chemical and biological properties of a new platinum (II) complex where the aromatic amino group of procaine is involved in the coordination with platinum and whose structure was defined by UV, IR, 1H-NMR, and elemental analysis. This new cationic platinum-triamine complex (DPR) displays excellent solubility (> 50 mg/ml) and stability in water. DPR has significant in vitro cytotoxicity against murine P388 leukemic cell line, human K562 erythroleukemic cell line and human Jurkat T cell line. The in vitro cytotoxic effects of DPR on P388 and Jurkat leukemic cells were comparable to those of cis-diamminedichloroplatinum (II) (DDP), while its activity on K562 cells was significantly better than that of DDP [IC50 = 1.07 +/- 0.36 (SD) microM vs 2.62 +/- 0.23 (SD) microM, P < 0.01]. The in vitro Pt accumulation rate for P388 cells was twice as rapid after DPR than after DDP exposure, while no difference in cellular platinum efflux was observed. The antitumor activity of DPR was tested in vivo against P388 leukemic cells in BDF1 mice and gave a % ILS value (75%) similar to that of the maximum tolerated dose (MTD) of DDP (8 mg/Kg). A comparative study of plasma urea nitrogen (PUN) levels and kidney morphological analysis in tumor-bearing mice receiving the LD50 dose of both drugs (39.3 mg/Kg and 16.5 mg/Kg for DPR and DDP, respectively), showed DPR to be less nephrotoxic than DDP. These results indicate that this new cationic platinum-triamine complex containing primary amine ligand is surprisingly active both in vitro and in vivo. In summary, the good characteristics of DPR in terms of high solubility, encouraging anticancer activity and absence of nephrotoxic effects make DPR a promising new platinum anticancer agent for preclinical development. PMID- 1295475 TI - Characterization of nuclear size, ploidy, DNA histogram type and proliferation index in 79 nerve sheath tumors. AB - The distribution values of ploidy, of the DNA histogram type, of the proliferation index and of the nuclear area are described in a series of 79 nerve sheath tumors including 7 traumatic neuromas, 55 primary and 9 recurrent benign schwannomas, 5 benign neurofibromas and 3 malignant tumors. The nuclear parameters were computed on Feulgen-stained nuclei (from archival formalin-fixed paraffin-embedded materials) by means of digital cell image analysis. The results show that 20-30% of benign nerve sheath tumors exhibit an abnormal nuclear DNA content (DNA index > 1.30). Such a feature was observed in the four groups of benign tumors, i.e. primary and recurrent schwannomas, neurofibromas and even traumatic neuromas. Aneuploid tumors exhibited triploid, hypertriploid or polymorphic DNA histogram types. The three malignant tumors under study were aneuploid. Lastly, the nuclear area and proliferation index measurements did not allow any clear distinction to be made between the four groups of benign tumors on the one hand, and between the benign and malignant tumors on the other. PMID- 1295477 TI - Tissue-specific induction of metallothionein by bismuth as a promising protocol for chemotherapy with repeated administration of cis-diamminedichloroplatinum (II) against bladder tumor. AB - The effects of bismuth nitrate pretreatment on the toxicity and antitumor activity of repeatedly administered cis-diamminedichloroplatinum (Cisplatin; CDDP) were examined using nude mice inoculated with human bladder tumor tissues. Lethal and renal toxicities exerted by the repeated administration of CDDP were effectively prevented by pretreatment with bismuth (Bi) without affecting its antitumor activity against transplanted human bladder tumor as in the case of single dose of the drug reported previously. The renal Bi level was gradually increased with the frequency of Bi administration, and metallothionein (MT) induced by Bi in the kidneys maintained its substantially high level during the treatment. It was confirmed that MT was not induced in the tumors even by the 5 cycles of repeated Bi administration. This specific protection shown by the Bi preadministration against the toxicity of repeatedly injected CDDP can be explained by the fact that Bi markedly induces MT in the kidney, a major target organ of CDDP toxicity, but not in the tumor tissues inoculated in the nude mice, probably because Bi is efficiently taken up by the kidney but hardly incorporated into the tumor tissues as reported previously. These data obtained by repeated doses of CDDP as described above strongly suggest a promising protocol for chemotherapy using CDDP with Bi compounds, a tissue specific MT inducer, against advanced bladder tumor in human. PMID- 1295478 TI - A prospective study of the value of imaging, serum markers and their combination in the diagnosis of pancreatic carcinoma in symptomatic patients. AB - The diagnostic accuracy of ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and tumour markers CEA, CA 50 and CA 242 in pancreatic cancer (n = 26) was studied in 113 patients with jaundice, in 20 patients with unjaundiced cholestasis, and in 60 patients with the suspicion of chronic pancreatitis or a pancreatic tumour. The sensitivities of US, CT and ERCP were 61.9%, 95.2% and 82.3%, the specificities 93.9%, 92.9% and 94.1%, and the efficiencies 91.6%, 96.6% and 92.1%, respectively. The sensitivities of CEA, CA 50 and CA 242 were 92.3%, 96.1% and 61.5%, the specificities 59.2%, 58.0% and 95.2%, and the efficiencies 63.7%, 63.2% and 90.6% respectively. The combined use of the imaging methods and tumour markers was also analysed. When either the imaging method or the serum marker test was required to be positive, the sensitivities of the combinations were clearly better than those of US and CA 242 alone, but only slightly better than those of CT, ERCP or the tumour markers CEA and CA 50 alone. When both the imaging test and the marker test were required to be positive, the specificities of the combinations were clearly better than those of CEA and CA 50 alone, but they did not exceed the specificity of the imaging methods or CA 242 alone. We conclude that CT, ERCP and CEA and CA 50 are highly sensitive in the diagnosis of pancreatic cancer in symptomatic patients, while the sensitivity of US and CA 242 is lower. The specificity of the imaging methods and CA 242 is high, but that of CEA and CA 50 is low. Imaging methods and serum tumour markers could be more used in clinical practice in a complementary manner. In patients with jaundice and/or cholestasis or with a suspicion of pancreatic tumour or chronic pancreatitis, the combined use may yield higher sensitivity than US alone and higher specificity than CEA or CA 50 alone. PMID- 1295479 TI - Uncommon mesenchymal tumors of the liver. Light microscopy, ultrastructure, immunohistochemistry and literature review. AB - This report presents the gross morphology, cytological, histological, ultrastructural and immunohistochemical features of two angiomyelolipomas of the liver. Diagnosis and classification of these tumors is difficult. There is no immunohistochemical and ultrastructural confirmation for Ito-cell pathogenesis of hepatic angiomyelolipomas. PMID- 1295480 TI - Immunohistochemical detection of mutant p53-suppressor gene product in patients with breast cancer: influence on metastasis-free survival. AB - Overexpression of p53-protein appears to be a common event in primary breast cancer. It has been proposed that the presence of elevated levels of this protein may be an independent prognostic factor and may be important for the ability of a tumor to metastasize. This study was performed to evaluate the influence of immunohistochemically detectable mutant p53-protein on metastasis-free survival of patients with breast cancer. Immunohistochemistry was performed on 117 paraffin-embedded biopsy specimens of consecutive patients with stage T1-T4 breast cancer, using a monoclonal antibody against p53 suppressor gene product. 29 (24.8%) specimens showed positive staining, whereas in 88 (75.2%) a negative staining reaction for p53 was found. Comparing time intervals to diagnosis of metastasis, using Kaplan-Meier curves, Log-Rank test revealed no significant differences in metastasis-free survival between p53 positive and negative patients (P = 0.32), whereas statistically significant differences were noted for tumor stage (P < 0.01), nodal status (P < 0.01), histological grading (P < 0.01) and estrogen receptor status (P = 0.03). Mutant p53-protein, as detected by immunohistochemistry in paraffin embedded tumor tissue, does not appear to influence metastasis-free survival in patients with breast cancer. PMID- 1295481 TI - Studies of the digestibility of pigs fed dietary sucrose, fructose or glucose. AB - Digestion of sucrose, fructose and glucose was studied in pigs with reentrant cannulas in the distal ileum or intact pigs fed diets formulated with sucrose, fructose and glucose as the major energy source and torula yeast. Sucrose and glucose were completely digested in the small intestine (apparent digestibility, 98.3 and 98.3%, respectively but a fraction of the dietary fructose escaped to the large intestine (adjusted value, 11.7%). There was no carbohydrate in rectal contents of the pigs. There was no carbohydrate influence on the pre-caecal or total digestibility of nitrogen. PMID- 1295482 TI - [The extraction particles from winter rapeseed with different glucosinolate fractions in swine with regard to the iodine supply. 3. Apparent digestibility of crude nutrients with special regard to the carbohydrate and nitrogen balance]. AB - In two digestibility and N-balance experiments the following solvent extracted meals were examined in a grain (barley and wheat in equal parts) or in a starch diet with four female pigs/group fitted with urethra catheters during the 5 days sampling period: 48% soyabean meal (SBM) (1), 24% conventional rapeseed meal (RSM) (2), 24 (3) or 48% (4) RSM from a newly bred low glucosinolate variety, groups 1 to 4 with grain, 48% low glucosinolate RSM (5) or 48% SBM (6) both with starch. In numeric order of the groups 88, 85, 86, 84, 79 and 89% N were digested. Pigs responded to the additional faecal N excretion from RSM diets by a lower urinary N excretion and thus they reached the N-balance of the animals fed on SBM. In numeric order of the groups 86, 79, 80, 73, 73 and 92% of the organic matter of the solvent extracted meals were digested. In comparison with SBM even 48% RSM in the feed significantly lowered the digestibility of organic matter. Using detergents the additional faecal organic matter excretion of RSM versus SBM could quantified as two third lignin. In the case of 24% RSM in the diet--i.e. 15% of the carbohydrates given--the carbohydrate digestibility is estimated with a high error, that an energetic feed value should not calculated. Investigating 48% SBM or RSM respectively in a grain diet the net energy content was 9.8 MJ (666 Energetic Feed Units, EFU pig) or 8.3 MJ (569 EFU pig)/kg dry matter (DM). Based on the starch diet, however, little relevant for estimation of normal pig diets, there were evaluated 10.6 MJ (720 EFU pig) for SBM and 8.3 MJ (567 EFU pig) net energy/kg DM for RSM. PMID- 1295483 TI - [Effect of the manganese content in laying hen feed with different Ca and mineral levels on the egg shell quality and bone mineralization of hens]. AB - Four experiments with 270, 44, 432 and 66800 Leghorn hens were carried out to investigate the influence of various Mn additions to diets differed in mineral or Ca contents on egg shell quality. The addition of 300 mg Mn/kg diet improved significantly egg shell breaking strength by 4 N over one year. The supply of 50 500 mg Mn/kg diet for 10-24 weeks of the second half of laying year did not influence the egg shell quality. Addition of mineral mixture or Ca grit to layer rations with adequate or higher Mn levels did not influence egg shell strength. High mineral content in a low manganese diet increased number of cracks by 3%. Strength, weight and ash content of tibia were significantly reduced by feeding a low mineral level. Addition of 50-150 mg Mn per kg low mineral diet normalized partially tibia stability in young hens. It was concluded that supplied dietary Manganese influences calcification positively only in young hens. High levels of Ca did not influence the effects of Mn. 50 mg Mn per kg layers mixture have been considered as an essential supply. PMID- 1295484 TI - DAP-decarboxylase activity and lysine production by rumen bacteria. AB - The last step of pathway of lysine biosynthesis by rumen bacteria was tested. The first measurements of DAP-decarboxylase activity and of lysine production by Megasphera elsdenii, Selenomonas ruminantium, Clostridium spp., Butyrivibrio fibrisolvens and Bacteroides succinogenes as well as the first attempts to increase the lysine production by ruminal streptococci by mutation are described. The highest values were measured in Selenomonas ruminantium (DAP-decarboxylase activity = 146 micrograms DAP.min-1.mg-1 protein and lysine production was 390 micrograms.mg-1 protein) and the lowest values were ascertained in Butyrivibrio fibrisolvens (DAP-decarboxylase activity = 27 micrograms DAP.min-1.mg-1 protein and lysine production was 32 micrograms.mg-1 protein). DAP-decarboxylase activity was increased by mutation especially in Streptococcus bovis, the lysine production in both of tested ruminal streptococci. The potential use of lysine excreting mutants in calves in future is suggested. PMID- 1295485 TI - Digestion and performance responses to lasalocid and concentrate supplements by beef cattle fed bermudagrass hay. AB - Beef cattle consuming bermudagrass hay were not supplemented or received a limited amount of ground corn alone or with a mix of protein meals to determine influences of concentrate supplementation on digestion and performance when the ionophore lasalocid (200 mg daily) was given. With limited feed intake, supplement treatment did not change the acetate to propionate shift in beef cows occurring with lasalocid (P < 0.06). Lasalocid did not affect sites of digestion of organic matter or nitrogen with any supplement treatment. However, lasalocid decreased (P < 0.10) ruminal digestion of neutral and acid detergent fibre. Live weight gain by growing beef calves ingesting bermudagrass hay ad libitum was higher (P < 0.05) with than without supplementation and tended (P < 0.12) to be greater for corn plus protein meals than for corn alone. Lasalocid did not affect or interact with supplement treatment in feed intake or live-weight gain of heifers (236 kg; no growth stimulant) or steers (237 kg; treated with 200 mg progesterone and 20 mg estradiol benzoate). Lasalocid at 200 mg daily did not improve digestion characteristics or influence performance by beef cattle consuming a Basal diet of bermudagrass hay. Further, effects of lasalocid were not modulated by supplementation with concentrate, concentrate type or sex or growth stimulant usage. PMID- 1295486 TI - DNR in the OR. PMID- 1295487 TI - Re: "Vasectomy and the risk of prostate cancer". PMID- 1295488 TI - An occupational health service in primary care. PMID- 1295489 TI - Does electromagnetic radiation cause cancer? PMID- 1295490 TI - Guidelines for local research ethics committees. PMID- 1295491 TI - Temperature- and concentration-dependence of compatibility of the organic osmolyte beta-dimethylsulfoniopropionate. AB - The effects of the organic osmolyte beta-dimethylsulfoniopropionate (DMSP) on the structural stability of three model proteins were examined to determine whether DMSP, like the structurally similar solute dimethyl sulfoxide (DMSO), is compatible with native protein structure at low, but not elevated, temperatures. DMSP stabilized phosphofructokinase under conditions of cold-induced denaturation. Thus, DMSP, like DMSO, may be an effective protein cryoprotectant. However, DMSP was not an effective stabilizer of protein structure under conditions of heat denaturation. Whereas low (0.2 M) concentrations of DMSP stabilized lactate dehydrogenase against inactivation at 50 degrees C, higher DMSP concentrations were ineffective. DMSP favored the denaturation of glutamate dehydrogenase at all DMSP concentrations tested. DMSP may be a compatible osmotic solute only under conditions of moderate temperature and low, yet physiological, concentrations. The mechanistic basis of DMSP's temperature- and concentration dependent effects and the possible roles played by adaptation temperature and severity of osmotic stress in the evolutionary selection of organic osmolytes are discussed. PMID- 1295493 TI - Pulsatile flow visualization in the abdominal aorta under differing physiologic conditions: implications for increased susceptibility to atherosclerosis. AB - The infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta. PMID- 1295492 TI - Photolabelling of Salmonella typhimurium LT2 sialidase. Identification of a peptide with a predicted structural similarity to the active sites of influenza virus sialidases. AB - The sialidase from Salmonella typhimurium LT2 was characterized by using photoaffinity-labelling techniques. The well-known sialidase inhibitor 5 acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non- 2-enonic acid (Neu5Ac2en) was modified to contain an amino group at C-9, which permitted the incorporation of 4-azidosalicylic acid in amide linkage at this position. Labelling of the purified protein with the radioactive (125I) photoprobe was determined to be highly specific for a region within the active-site cavity. This conclusion was based on the observation that the competitive inhibitor Neu5Ac2en in the photolysis mixture prevented labelling of the protein. In contrast, compounds with structural and chemical features similar to the probe and Neu5Ac2en, but which were not competitive enzyme inhibitors, did not affect the photolabelling of the protein. The peptide interacting with the probe was identified by CNBr treatment of the labelled protein, followed by N-terminal sequence analysis. Inspection of the primary structure of the protein, predicted from the cloned structural gene for the sialidase [Hoyer, Hamilton, Steenbergen & Vimr (1992) Mol. Microbiol. 6, 873-884] revealed that the label was incorporated into a 9.6 kDa fragment situated within the terminal third of the molecule near the C-terminal end. Secondary-structural predictions using the Garnier-Robson algorithm [Garnier, Osguthorpe & Robson (1978) J. Mol. Biol. 120, 97-120] of the labelled peptide revealed a structural similarity to the active site of influenza A- and Sendai-HN-virus sialidases with a repetitive series of alternating beta sheets connected with loops. PMID- 1295494 TI - Cage allocation designs for rodent carcinogenicity experiments. AB - Cage allocation designs for rodent carcinogenicity experiments are discussed and presented with the goal of avoiding dosage group biases related to cage location. Considerations in selecting a cage design are first discussed in general terms. Specific designs are presented for use in experiments involving three, four, and five dose groups and with one, four, and five rodents per cage. Priorities for balancing treatment groups include horizontal position on shelf and shelf of rack, nearest neighbor balance, and male-female balance. It is proposed that these balance criteria be considered together with practical issues, such as the ability to accurately conform to a design and to determine a sensible and efficient design for each experiment. PMID- 1295495 TI - Shipbuilding and ship repair. PMID- 1295496 TI - Estimating gallstone incidence from prevalence data. AB - Because incidence data for gallstones are generally unavailable, we have used a previously described epidemiologic method to estimate age-specific incidence rates from published gallstone prevalence data in seven populations. Yearly incidence rates ranged from a low of 1 in 1000 for the younger men to 19 in 1000 for the oldest women. An overall pattern of increasing incidence of disease with increasing age was observed. Rate-ratios for oldest versus youngest subjects ranged from 4.0 in German women to 9.4 in Italian men: mean rate-ratio = 5.9; 95% CI = 4.0-7.8. For all centers, age-specific female incidence rates exceeded comparable age-specific male rates at all ages (mean female to male rate-ratio = 1.85; 95% CI = 1.7-2.0). No differences were observed in the sex-specific incidence of gallstones for subjects of similar age in the various centers (P = > 0.10). For Denmark our estimates resemble recently published incidence data obtained by re-surveying the original population. PMID- 1295497 TI - [Role of home monitoring in the context of sudden infant death prevention. Current methods indications, monitoring]. AB - Some infants are cared with a home monitoring system during their first year of life. An international clinical consensus has been obtained and has proposed this technique mainly for infants who have presented an apparent life threatening event or for ex-premature with bradycardia or apnea, rather than for siblings of sudden infant death syndrome or other infants. In any case, this monitoring must be held after a complete clinical evaluation of the infant and after a real education of the parents about the use of the device. Many types of devices are used. The most efficient is the cardio-respiratory monitoring. Some of them include a processor and record the alarms. The need to see or to call the medical team to decode them allows close collaboration between the family and the clinical team. Knowledge of the alarms and the circumstances in which they have occurred help the medical team to propose the withdrawal of the home monitoring. Thus, sometimes preventive, sometimes prophylactic, this device will provide us for an optimal help. PMID- 1295498 TI - [Pain from distinct points of view]. PMID- 1295499 TI - Collagen and liquid silicone injections. PMID- 1295500 TI - Carotid endarterectomy in Puerto Rico. AB - The experience of the authors performing carotid endarterectomy in Puerto Rico is reported. The study was stimulated by the recently published results of the Carotid Endarterectomy Cooperative Trial groups in North America and Europe. This series consists of 61 carotid endarterectomies performed on 53 patients. The majority of the patients suffered from hypertension, diabetes mellitus, smoking, and ischemic heart disease. Most of the patients presented with Transient Ischemic Attacks (64%) or Reversible Ischemic Neurologic Deficits (19%). One patient died of a presumptive myocardial infarction and one patient had a post operative worsening of his neurologic condition. The permanent morbidity and mortality rate was 3.2%. PMID- 1295501 TI - Cardiac surgery on Jehova's Witnesses at Instituto Cardiovascular-Hospital Pavia. AB - Jehovah's Witnesses (J.W.) can undergo successful cardiac operations. We have operated five J.W. patients. Of these patients, two had coronary artery bypass surgery and three had correction of congenital anomalies. These included an atrial septal defect with infundibular pulmonic stenosis, a tetralogy of Fallot and a patient with a ventricular septal defect. Our treatment protocol includes a meticulous surgery, the use of early heparinization to collect all shed blood into the pump oxygenator, observation in the operating room for early exploration if the patient bleeds and administration of iron preparations. Recombinant human erythropoietin, although available and in our treatment protocol, has not been used yet. All patients survived the operation and left the hospital with an excellent hemoglobin and hematocrit. The length of stay varied from 7 to 15 days. PMID- 1295502 TI - Usefulness of single fibrinopeptide A determination in patients with acute ischemic coronary artery syndromes. AB - Coronary artery thrombosis plays a major role in the acute ischemic coronary artery syndromes in which fibrinopeptide A (FPA) has proved to be a sensitive marker. The purpose of this study was to determine FPA concentrations in patients with acute coronary artery syndromes and to determine if these could serve as a short-term prognostic indicator. Single plasma FPA levels were measured in 26 patients with acute ischemic coronary artery syndromes within 24 hours of the onset of chest pain as well as in 12 patients with chronic stable angina and in 9 control subjects. Higher FPA levels were observed in patients with unstable angina whom later developed recurrence of chest pain compared to those without (8.1 +/- 3.4 vs. 3.4 +/- 2.2; p = 0.01). Neither the localization of ischemia, presence of complications, need for revascularization nor short-term prognosis (6 months) correlated with the plasma FPA concentration. Therefore, except for recurrence of chest pain in patients with unstable angina, the finding of an elevated FPA level upon admission did not provide additional information regarding clinical course and prognosis than that obtained in a detailed clinical history, physical examination and initial electrocardiogram in patients with acute ischemic artery syndromes. PMID- 1295503 TI - Cardiopulmonary resuscitation personal choices of physicians and nurses. AB - Nine hundred and twenty-two attending physicians, residents and graduate nurses in five hospitals were requested to state their personal preference to receive either cardiopulmonary resuscitation (CPR) or intubation and mechanical ventilation (MV) when given three estimated outcomes: 1) complete recovery, 2) important loss in mental and physical functions, c) persistent unconsciousness. They also could choose not to accept either procedure. Seventy three percent would accept CPR and 70 percent MV, only if complete recovery was likely. Thirteen percent would accept CPR and MV if important losses of function were likely. Eight percent would accept CPR and 5 percent would accept MV if recovery of consciousness was unlikely. Six percent would not accept CPR and eleven percent would not accept MV under any circumstance. Men and women differed in the choice of outcomes which made resuscitation acceptable to them (p < .001). More women than men would accept CPR and MV if complete recovery was likely and were unwilling to accept CPR or MV under any circumstance at all. Half as many women as men would accept MV if they were likely to remain unconscious. Choices also varied with age and professional training. There are large individual differences as to how physicians and nurses would like their personal cardiopulmonary arrest to be managed. Their choice is appropriately influenced by the expected outcome and seems to be influenced by the local hospital setting. PMID- 1295504 TI - Hypertension: pathophysiologic-based management. Part II. AB - The therapy for hypertension utilizing diuretics and beta-blockers induces metabolic and biochemical alterations that blunt the possible beneficial effects of blood pressure reduction in coronary artery disease risk. The utilization of other antihypertensive medications with the capacity of improving cardiovascular risk factors, like diabetes and dyslipidemias is recommended. PMID- 1295505 TI - [Comments on cardiopulmonary resuscitation. We should resuscitate the dead when indicated and allowed]. PMID- 1295506 TI - Children and adults: comparing the risks from exposure to exogenous substances. PMID- 1295507 TI - Working with the elderly: do student nurses care for it? AB - This study investigates neophyte student nurses' attitudes to working with the elderly through placing them in relation to attitudes to other nursing career options and by exploring student nurses' reasons for such attitudes. The results are based on a questionnaire answered by 610 students from five NSW teaching institutions. The results indicate that nurses rate working with the elderly very poorly, and that this negativity is based on unfavourable stereotypes of aged persons and their care. These findings are placed in the context of projected demographic changes and the pressures these will place on the health care system and its need for nurses qualified in this area of work. PMID- 1295508 TI - Child immunisation levels in Sydney's Western Metropolitan Region: parental attitudes and nurses' roles. AB - Research was undertaken to examine childhood immunisation uptake rates, parental attitudes towards immunisation and immunisation services and parents' perceptions of health workers' (especially nurses') contribution to immunisation in the Western Metropolitan Region of Sydney, NSW. After a pilot study a questionnaire was distributed by teachers to a random sample of 450 parents of kindergarten children living in the Region. Data revealed an 84% childhood immunisation rate for all scheduled immunisations up to five years with a partial immunisation rate of 10% (6% did not answer or had gaps in immunisation information). The most significant factors associated with partial immunisation were found to be the socioeconomic and educational status of the children's fathers and itinerancy. Parents of partially immunised children were significantly more likely than parents of totally immunised children to consider that serious side-effects to immunisation do occur. The research also found that parents have a knowledge deficit about the seriousness of measles; that immunisation services in the Region have significant deficiencies and that nurses have a low profile and poor image in the provision of those services. As Early Childhood nurses were considered by parents as providing the most appropriate immunisation nursing service, their further involvement in promoting and extending services is recommended. PMID- 1295509 TI - Nurse practitioners' and students' attitudes towards people with disabilities. AB - This article reports the results of assessments of nurse practitioners' and nursing students' attitudes toward people with disabilities. Findings of three projects that used the Interaction with Disabled Persons Scale suggest that Australian nurses' and nursing students' attitudes are more positive than those of the general population and that nurse education strategies are effective in promoting positive attitudes. These findings contrast with the results of overseas studies which indicate that health professionals' attitudes toward people with disabilities are negative and unaccepting. PMID- 1295510 TI - Handover: the collective narrative of nursing practice. AB - This paper examines the practice of handover in a large metropolitan hospital. It shows that the handover is a significant site at which to examine how tensions and imperatives derived from the traditional institutional position and role of the nurse are played out in contradiction with emergent professionalism. It identifies handover dimensions and focuses discussion on how the collective narrative of the handover serves to construct patient identities as well as ensure solidarity and cohesion among nurses. PMID- 1295511 TI - Queen Elizabeth Behavioural Assessment Graphical System. AB - The Queen Elizabeth Behavioural Assessment Graphical Scale (QEBAGS) is presented as a new, descriptive rating method for documenting behavioural disturbances in a variety of clinical settings. The scale utilises three categories of behavioural disturbances which may occur in isolation or may co-exist. These are documented on a graphical plot across a 24 hours' time span. Neither diagnostic information nor severity of a particular behavioural disturbance needs to be interpreted before a rating on each parameter can be made, thus allowing its use by any intelligent observer, including a carer at home. Documenting of behavioural disturbance across day and night, by intermittent or regular observations, provides valuable information on the time, course and pattern of behavioural disturbance, from which diagnostic and therapeutic directions can be inferred. In preliminary clinical use, the scale has improved documentation of behavioural disturbance and communication between health professionals about such behaviour and its management. The scale also has the potential to provide supportive documentation for the Resident Classification Index in Nursing Homes and Personal Care Assessment Index in Hostels. The scale is most effective in situations where moderate to severe disturbance of behaviour is present. Where there is little or no disturbance, the system is unlikely to be of benefit. Clinical examples of its utility are presented. PMID- 1295512 TI - [Changes due to age in the regenerating axons of the adult rat]. AB - Muscle reinnervation after nerve crush was observed in rats at different ages with a combined technique that simultaneously demonstrates nerve endings and endplates. At early times of reinnervation the amount of sprouting was higher in older rats than in younger rats; according to this finding an enhanced number of polyinnervated endplates was found in older rats. A similar enhancement of sprouting and polyinnervation was observed during muscle reinnervation of vitamin E deficient rats, supporting the proposed analogy between vitamin E deficiency and aging. PMID- 1295513 TI - Calcium adenosinetriphosphatase of bovine retinal rod outer segment disks. AB - A Ca(2+)-pumping ATPase activity is present in bovine retinal rod outer segment purified disks. The ATPase has a high Ca2+ affinity (KM = 25 microM). Low Ca2+ (n microM) concentrations stimulate an ATP-dependent Ca2+ uptake and the ATP hydrolysis in the absence of exogenous Mg2+. Electrophoretic analysis of disk proteins after treatment with (gamma-32P)ATP shows the existence of the enzyme phosphate acid-stable, hydroxylamine-sensitive intermediate complex of molecular mass of about 135 kDa. The results would indicate the presence of an inwardly directed Ca(2+)-ATPase pump acting on the disk membrane, that could be involved in the regulation of cytosolic free Ca2+ levels inside ROS. PMID- 1295514 TI - [Fluorocytometric study of proliferation antigens, nuclear proteins and ploidy in acute leukosis]. AB - P53 protein, Ki67 proliferative associated antigen and DNA content have been studied by flow cytometry in the blood blastic cells from 41 patients with acute leukemia. The results were compared with the F.A.B. classification. Cells were permeabilised and fixed by PLP solution before using the FITC conjugated Ki67 MoAb and the p53 MoAb (clone 1801). Propidium iodide and RNAase has been used in order to determine ploidy. Ki67 and p53 protein were found to be expressed at higher level in leukemia cells than in normal bone marrow cells; however there was no correlation between Ki67 and p53 expression and F.A.B. subtype. In acute leukemia patients the range of positivity of Ki67 was 1.1-52.1% while it ranged from 1.8% to 80.1% for the p53 protein. On the basis of these findings we conclude that the flow cytometry evaluation of Ki67 and p53 represents a useful tool for the study of the biologic characteristics of the leukemic cells in patients with acute leukemia. PMID- 1295516 TI - Ascorbate peroxidase activity in resistant and susceptible plants of Lycopersicon esculentum. AB - Activity of redox-enzymes of AA system and of catalase was measured in two near isogenic tomato lines, respectively resistant and susceptible to Tobacco Mosaic Virus infection. AFR reductase, DHA reductase and catalase showed quite similar activities in both lines, whereas AA peroxidase activity in resistant plants was 75% higher than in susceptible ones, with Km values about 4-fold lower. These data suggest that hydrogen peroxide scavenging operated by AA peroxidase could play an important role in the development of biological defence mechanisms against pathogens. PMID- 1295515 TI - [Effect of ASA on the interaction of von Willebrand factor with the platelet membrane]. AB - Ristocetin induces a conformational change on von Willebrand Factor (vWF) similar to that due to the interaction with the subendothelium, by which the former can interact with the Glycoprotein-1 B (GPIB) of the platelet membrane and trigger aggregation and granule content secretion. Platelet Rich Plasma (PRP) treated with Acetyl Salicylic Acid (ASA) loses completely the aggregability induced by addition of Ristocetin whereas ASA-treated and successively Washed Platelets (AWP) supplemented with normal plasma (PPP) give an aggregation and a secretory response to Ristocetin similar to that given by PRP; similarly normal Washed Platelets (WP) supplemented with ASA-treated plasma (APPP) give identical aggregation, and secretion by Ristocetin addition. Ours results indicate that the Ristocetin-vWF complex can trigger two distinct intraplatelet metabolic pathways. A first well known way starts from the activation of Phospholipase A-2 (PL-A2), by which arachidonic acid is produced, that, in turn, undergoes the metabolic pathway leading to Thromboxane A-2; this pathway can be blocked by the intraplatelet ASA by irreversible inactivation of Cyclooxygenase, but it is insensitive to the extra-platelet ASA. A second, independent metabolic pathway, can be triggered by intact vWF, but not by the ASA treated one. It is insensitive to intraplatelet ASA and therefore unrelated to the arachidonic acid metabolism. This pathway could start from the activation of Phospholipase C (PL-C). PMID- 1295517 TI - Single stranded DNA-vectors for analyzing processing of DNA damage induced by 4 nitroquinoline-1-oxide in prokaryotes and eukaryotes. AB - Previous studies indicate that single stranded DNA vectors could be used in different organisms to study mutagenesis induced by DNA damaging agents. We applied this approach to study mutagenesis induced by 4NQO lesions. The use of ssDNA, on which the ultimate metabolite of 4NQO (Ac-4HAQO) induces mainly C8 guanine adducts, allowed us to find a correlation between G-transversions and the dGuo-C8-AQO adduct. This correlation was established in two independent assay systems, based on prokaryotic and eukaryotic cells. PMID- 1295518 TI - Investigation of the patterns of argyrophilic nucleolar organiser regions (AgNORs) in primary gastric lymphomas. AB - Eight cases of primary gastric lymphomas have been investigated by AgNORs method to individualize the patterns of distribution of NORs. Modifying and exemplifying the scheme of Nikicicz and Norback, previously applied to blood smears and bone marrow in patients affected by leukaemia, the authors found 8 principal distribution patterns of AgNORs. Recording the percentage of the single patterns in every case it was possible to individualize two quite homogeneous groups. The authors maintain that in this way, avoiding complex numerical evaluations and statistical analysis, it is possible to easily classify the gastric lymphomas. We suggest that an improvement of the results could be achieved by comparing the immunophenotype of the cellular lymphomatous populations, and the AgNORs pattern with patients survival. PMID- 1295519 TI - [Psychoacoustic tests: effects of atropine]. AB - The efferent pathways exert a control action on the function of the cochlear nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal system and its action can be blocked by atropine. In order to give a contribution to the knowledge of the function of the efferent bundle and of the cochlea efficiency we examined 10 young normal subjects before and after infusion of 1 mg of atropine i.v. a battery of three psychoacoustical tests (Remote Masking, Critical Ratio and Brief Tone Audiometry). After infusion of atropine we have shown an increase of 0.25 Hz hearing threshold, an increase of RC values and a decrease of RM values. It can be concluded that the pharmacological block of the olivo-cochlear bundle determines a stiffness of outer hair cells and basilar membrane; this finding means that the atropine can inhibit the facilitating activity of the efferent system on the cochlear performance. PMID- 1295521 TI - Undergraduate ophthalmology teaching. PMID- 1295520 TI - [Polyester treatment in rats with a dorsal air pouch: chemotaxis in lavage fluid from the pouch]. AB - Minced polyester threads introduced into peritoneal cavity of rats cause a granulomatous inflammation with evidence of macrophage stimulation. Chemotactic agents play an important role in the inflammatory reaction; they are released locally by cells involved in inflammation. In this paper the chemotactic effect of the peritoneal and subcutaneous air pouch fluids from rats bearing the polyester inflammatory process, have been studied on PMN cells "in vitro". The fluids were obtained by washing the cavity of untreated rats or rats injected with polyester, 7 days after the injection. The chemotactic response was assayed by employing modified chemotaxis Boyden chambers (Blind Well Neuro Probe) and polymorphonuclear cells from normal rats. Quantification of the migration was calculated by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrate that a chemotactic activity is present in peritoneal and subcutaneous air pouch fluids following the inflammatory process. In conclusion the chronic inflammation determines the appearance of chemotactic factors for PMN cells, in the peritoneal cavity and in the air pouch, and the air pouch is a very convenient experimental system with the particular advantage that it permits easy repeated sampling of exudate during the course of an inflammatory response. PMID- 1295522 TI - Informed consent. PMID- 1295523 TI - Problems of deep foveas. AB - Deep or convexiclivate foveas occur in some birds, including raptors, some lizards and certain deep-sea fishes. Theories on their function are reviewed. Common to raptor and deep-sea fish foveas is a radial fibre lining, dark staining so probably optically dense, adjacent to the less refractile vitreous. The foveal curvatures and size are remarkably similar in a wide taxonomic and size range of birds and fishes. Ray plotting through traced foveal outlines suggests that sharp images will be formed beneath the centre and shoulders, with the centre image enlarged enough to account for the high acuity of raptors. Deep foveas will also exaggerate eccentricity of off-centre images of a point source, such as deep-sea fishes may meet. Despite similarities in foveal shape, the receptors differ widely between species. Raptors, and notosudid fishes, have short cones. Searsid fishes have long single rods. Howella and Bajacalifornia have multiple bank rods, more in the fovea than the periphery. Those of Howella are shown to be multiple inner-outer segment complexes rather than interrupted single rods. Implications of foveal and receptor features are discussed. PMID- 1295524 TI - Ophthalmology in the undergraduate curriculum. A review in Queensland. AB - Three hundred and sixty-nine postal questionnaires related to the content and teaching of the undergraduate medical course were sent to Queensland city and provincial ophthalmologists, general practitioners, physicians and surgeons. The return rate was 53%. The views of the four groups were similar in most respects. The majority of respondents thought that ophthalmology should be taught as a separate course. They stated visits to operating theatre and eye casualty unit should be included in the course. Ophthalmologists and general practitioners stated the course should be longer, physicians thought it should remain the same length and surgeons felt less time should be dedicated to the teaching of ophthalmology. Topic areas regarded as essential were the acute care areas: trauma; glaucoma; infection; use of an ophthalmoscope; acute visual loss; and red eye. Squint was also regarded as an essential area by ophthalmologists. PMID- 1295526 TI - A retinitis pigmentosa register for western Australia. AB - This paper describes the main elements of the Western Australian retinitis pigmentosa register including details of the data stored on the register, aspects of the coding systems used and some description of the tests employed in diagnosis of retinitis pigmentosa. The register is family based and contains data on affected individuals and on their unaffected relatives. As at November 1991, the register contained data for 391 individuals from 207 separate families. Of the 391 individuals, 240 had definite or probable retinitis pigmentosa and 26 were possibly affected. The remainder were unaffected family members. In many cases, both affected and unaffected family members are being studied serially and the register is designed to store and easily retrieve serial data to allow study of disease progression for individuals and within families. PMID- 1295525 TI - The effect of topical corticosteroids on laser-induced peripheral anterior synechiae. AB - PURPOSE: To assess the influence of different topical steroid agents and a non corticosteroid medication after Argon laser trabeculoplasty (ALT) on the development of peripheral anterior synechiae (PAS) and the reduction of intraocular pressure (IOP). METHOD: In two separate prospective, randomised, group-controlled studies, topical fluorometholone 0.1% (FML Liquifilm) was compared with dexamethasone 0.1% (Maxidex) (Study A), or naphazoline hydrochloride 0.1% (Albalon) (Study B) after ALT for chronic open-angle glaucoma, with particular reference to the formation of PAS and the IOP response. RESULTS: In Study A (N = 109) eyes treated with Maxidex had a significantly higher incidence of PAS than those treated with FML - 45% compared with 22%, P < 0.05 (normal deviate test). In Study B (N = 75) the incidence of PAS was equal in eyes treated with FML or Albalon (23%). In the two studies combined (N = 184), the development of PAS was associated with a significantly lower mean response of IOP to ALT - 1.47 mmHg compared with 3.22 mmHg, 0.01 < P < 0.05 (Student t-test). CONCLUSION: The incidence of PAS after ALT is significantly higher with the post laser use of Maxidex than with FML, and is the same for Albalon as for FML. The therapeutic benefit of ALT is significantly reduced if PAS develop. PMID- 1295527 TI - Optic neuritis in children with poor recovery of vision. AB - We reviewed the records of 10 children with optic neuritis in whom recovery of vision was poor or incomplete. Our cases were otherwise similar to those described in previous studies in that they were always bilateral, often accompanied by a viral prodrome (seven of 10), and usually associated with disc oedema (seven of 10). Seven of twenty eyes had a final visual acuity of 6/60 or worse and only one patient regained 6/6 vision in either eye. In three patients the best vision in either eye was 6/60 or worse. Recovery of vision was often slow, taking up to six years. Five of 10 patients have developed multiple sclerosis (MS), and one child had acute disseminated encephalomyelitis (ADEM) with optic neuritis. Optic neuritis in children does not always carry a good prognosis for recovery of vision; however, the failure of vision recovery in a short period of time does not necessarily indicate a poor outcome. Some children with optic neuritis develop MS, which can develop even when optic neuritis follows a viral illness. PMID- 1295528 TI - Haemangiopericytoma of the orbit. AB - Orbital haemangiopericytomas are ideally managed by complete surgical excision in the first instance. This is frequently not achieved, because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. A series of 12 patients with orbital haemangiopericytoma seen over a 23-year period is presented. The following combination of clinical and radiological features is suggestive of haemangiopericytoma. 1. Painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling. 3. A soft, superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium. 5. Significant blush in all three phases of carotid angiography, without prominent arteriovenous shunting. Once haemangiopericytoma is suspected, complete surgical excision is recommended. PMID- 1295529 TI - Paediatric dacryocystorhinostomy. AB - The results of 95 dacryocystorhinostomy procedures in 78 paediatric patients are reviewed. The success rate was 77%. Factors influencing success and failure are discussed. PMID- 1295530 TI - Superior sagittal sinus thrombosis--an unexpected cause of papilloedema. AB - Two patients with superior sagittal sinus thrombosis are reported. Papilloedema was an important diagnostic sign in both cases. Magnetic resonance imaging (MRI) provided the diagnosis in each case and proved to be the investigation of choice. Superior sagittal sinus thrombosis should be considered in the differential diagnosis of papilloedema as it is both potentially fatal and probably underdiagnosed. PMID- 1295532 TI - True exfoliation of the lens capsule. PMID- 1295531 TI - Preservation of residual field after surgical lowering of intraocular pressure. AB - A 52-year-old Caucasian woman with pigmentary glaucoma underwent a left cyclodiathermy procedure for raised intraocular pressure (IOP) in 1962 and right sclerectomy the following year. Over 25 years later a low IOP was still maintained though pilocarpine was needed in the left eye. After a left cataract extraction with insertion of a posterior chamber lens, field loss had not progressed very much in either eye though the visual acuity was reduced in the more affected eye. Both drainage operation and a cyclodestructive procedure controlled IOP over a long period of time in this patient and were associated with only a very gradual progression of field loss. PMID- 1295533 TI - The patulous popping punctum: confirmation of a positive Valsalva bubble test. PMID- 1295534 TI - Lacrimal probing. PMID- 1295535 TI - [Preparation and utilization of BrdU antiserum. II. Detections of BrdU labelling chromosome and DNA using BrdU antibody technique]. AB - Utilizing highly specific BrdU antiserum, via the second antibody conjugated with enzyme and DAB-H2O2 or AEC-H2O2 colorific methods, the BrdU marked regions of CHO and human chromosomes were detected clearly. The BrdU-DNA prints (pg) on nitrocellulose membranes were also showed with similar methods. PMID- 1295536 TI - [Studies of distribution of subtypes of transferrin, group-specific component, alpha 1-antitrypsin in gastric cancer patients from Shanghai area]. AB - The genetic polymorphism of transferrin (Tf) and alpha 1-Antitrypsin (alpha 1-AT) in 202 gastric cancer patients and 202 controls in Shanghai Hans were analyzed by isoelectric focusing. In transferrin, the phenotype frequency of C1C1 and gene frequencies of c1 and c2 were 0.3713, 0.5718 and 0.4109 respectively in gastric cancer patients, and 0.5149, 0.6782 and 0.2970 separately in controls. The frequencies of the c1c1 phenotype and the C1 gene increased significantly (p < 0.01) among the controls, while the frequency of the C2 gene greatly increased (p < 0.01) among the patients. The frequencies of the C2C2 in gastric cancer patients and controls were 0.2228 and 0.1436 respectively, showing a significant difference between them (p < 0.05). The genetic polymorphisms of group-specific component (Gc) in 200 gastric cancer patients and 200 controls in Shanghai Hans were studied with isoelectric focusing followed by immunofixation. The Gc1F1F phenotype frequency and 1Fgene frequency were 0.22 and 0.4375 in gastric cancer patients, and 0.14 and 0.3600 in controls, respectively. The frequencies of the Gc1F1F phenotype and the 1F gene were significantly increased (p < 0.05) among the patients. In alpha 1-Antitrypsin, there was no significant difference in phenotype frequencies and gene frequencies between the patients and controls. The data reported here indicate that the gastric cancer is associated positively with TfC2 and Gc1F, and negatively with TfC1. These facts support the notion that cancerogenesis is a multi-step process controlled by multifactorial inheritance. PMID- 1295537 TI - [Synaptonemal complexes of human spermatocytes and foetal oocytes observed by electron microscopy]. AB - The electron microscopical studies on the synaptonemal complexes (SC) of Chinese spermatocytes and foetal oocytes have been made and used to construct SC karyotype with a modified surface micro-spreading technique. We also confirm the SC formation between the short arms of the X chromosome and Y chromosome as well as secondary association between the distal tips of Xq and Yq at pachytene. Moreover, attentions are paid to the morphology of the XY pairs and five pairing type of XY pairs. In our preparations, a rare triploid spermatocyte was observed and triple pairing was described. Some possible significances of the triple pairing of triploid spermatocyte in relation to the human chromosomal abnormalities have been supposed. PMID- 1295538 TI - [Isolation and characterization of prolactin messenger RNA from bovine anterior pituitary glands]. AB - The messenger RNA was extracted from bovine anterior pituitary glands and was purified by oligo(dT)-cellulose chromatography. The length of the mRNA was 1,200 nucleotides measured by agarose gel electrophoresis containing methylmercury hydroxide. The bovine prolactin (PRL) mRNA was confirmed by Northern blot analysis of the mRNA with gamma-32P labelled synthetic oligonucleotide probes based on the partial amino acid sequences of bovine PRL and could stimulate the incorporation of 35S-methionine into protein in the rabbit reticulocyte cell-free system. The translation product of bovine PRL mRNA was immunoprecipitable by rabbit anti-ovine PRL anti-antibodies. The molecular weight of the translation product corresponding to the bovine PRL precursor was estimated to be approximately 25,000 by SDS polyacrylamide gel electrophoresis and autoradiograph. PMID- 1295539 TI - [Iterative estimation of variance components for a mixed model with a numerator relationship matrix: apply to compute K of variance ratio in BLUP and genetic parameters]. AB - An iterative procedure is presented for the estimation of variance components in the mixed model with a numerator relationship matrix from non-balanced data. This method has been shown to be feasible if only designing matrix for fixed effects of the mixed model and Henderson method 3 hypothetic condition of the fixed effect to compute correctly the reduction in sum of squares, we would obtain more precise estimation of variance components, furthermore, the sizes of the initial value K could not affect to last result of the iterative solution. This is because in the iterative process may adjust automatically by designing matrix. Also, the variance components could apply not only to compute variance ratio in BLUP, but also to estimate genetic parameters. PMID- 1295540 TI - [Nucleotide frequency analysis of bacteriophage phi X174 genome]. AB - Detailed analysis was carried out on the nucleotide frequencies in the genome of bacteriophage phi X174. In coding regions the distribution of four nucleotides at the three codon sites was highly non-random, and the patterns were conspicuously similar among the genes, implying that it might be a feature of the genome. An index c, which was based on the chi 2 statistics of the site by base 3 x 4 table, was introduced to reveal he extra information embedded in the coding region, and also to discriminate between coding and non-coding open reading frames. Doublet deviation analysis showed that deviation patterns were not significantly related to the codon sites in coding regions, and were also very similar in different genes. Possible mechanisms of such similarity are discussed. PMID- 1295541 TI - The antimicrobial activity of non-antibiotics: interactions with antibiotics. AB - The following are considered: the direct antibacterial activity of non antibiotics: resistance-reversing agents and resistance-inducing agents; the antibacterial and antiparasitic activity of non-antibiotics: psychotropics, antihistaminics, antineoplastics, allopurinol, hyperbaric oxygen, etc.; as well as the antibacterial activity of agents modifying the urinary pH; the influence of non-antibiotic drugs on the pharmacokinetic parameters of antibiotics; the anti infectious activity of non-antibiotics through their effects on host defences, immunity and inflammation, and finally the use of non-antibiotics to decrease the toxicity of anti-infectious agents. PMID- 1295542 TI - Antiplasmid activity: loss of bacterial resistance to antibiotics. AB - The antiplasmid activity of tricyclic compounds, e.g. phenothiazines, dibenzoazepines, dibenzocykloheptene derivatives and some stereoisomers, was shown on E. coli in vitro. Some ring-substituted phenothiazine and cannabis derivatives had only an antibacterial effect. Promethazine, a selected phenothiazine, cured antibiotic resistance and lactose fermentation of E.coli, tumour inducing ability of Agrobacterium tumefaciens and nodule formation of Rhizobium meliloti. Plasmids of different E.coli strains were eliminated with varying frequency. The antiplasmid activity of the compounds can be due to the increased membrane permeability. Inhibition of DNA gyrase and complex formation with the supercoiled form of plasmid DNA can lead to the cessation of plasmid replication in the bacterial cells. In addition, in vivo plasmid curing was demonstrated at a low frequency. PMID- 1295543 TI - The modulation of the bacteriolytic effect of beta-lactam antibiotics by non antibiotics. AB - The addition of cationic proteins such as lysozyme, ribonuclease and cytochrome C enhanced the beta-lactam-induced bacteriolysis of staphylococci measured as release of wall label or by optical density. The treatment of staphylococci with penicillin plus cytochrome C resulted in a reduced viability of bacteria compared with those treated with penicillin alone. The wall autolysis and the penicillin induced bacteriolysis of staphylococci were enhanced by the lysosomal enzyme cathepsin C. The penicillin-induced bacteriolysis was also enhanced by the D amino acids D-alanine and D-methionine, while the comparable L-amino acids did not reveal any activity. On the other hand, some polyanionic substances were able to suppress the penicillin-induced bacteriolysis. Radiochemical and electron microscopic studies revealed the participation of bacterial wall autolysins in the first steps of degradation processes of staphylococcal walls within murine bone marrow-derived macrophages. PMID- 1295544 TI - In vitro antimicrobial activity of 18 phenothiazine derivatives: structure activity relationship. AB - The antimicrobial activity of 18 phenothiazine derivatives has been evaluated against aerobic and anaerobic bacteria. The mean of the MIC reveals five active drugs against the bacterial strains tested: thioridazine, chlorpromazine, trifluoperazine, fluphenazine and triflupromazine. The other derivatives are less active and some show no antimicrobial activity. It seems that in vitro antibacterial activity alone is insufficient to explain certain intestinal diseases linked to the use of these molecules in psychiatry. PMID- 1295545 TI - The antimicrobial activity of non-antibiotics. Report from a congress on the antimicrobial effect of drugs other than antibiotics on bacteria, viruses, protozoa, and other organisms. AB - In May 1990 the 1st International Conference on Antimicrobial Activity of Non Antibiotics was held in Copenhagen, Denmark. More than 200 scientists were drawn from 34 countries and from all five continents. Papers were presented dealing with the antimicrobial activity of different synthetic and natural compounds, and interactions between antibiotics and non-antibiotics. The conference pointed to the unusual properties of non-antibiotic drugs. These effects might create unexpected therapeutic possibilities and lead to new basic insights. PMID- 1295546 TI - Microcirculation of the rat pancreas, with special reference to the insulo-acinar portal and insulo-venous drainage systems: a further scanning electron microscope study of corrosion casts. AB - Microcirculation in rat pancreas was studied by scanning electron microscopy of resin vascular casts and by light microscopy of India ink-injected and sectioned tissue samples. In the scanning survey of the casts, islets larger than 30 microns in diameter counted no less than 400 in the adult rat pancreas. They were located either in the exocrine lobules (intralobular islets, counting 210 or more), or in the interlobular tissue spaces and along the secretory ducts (extralobular islets, 190 or more). Every islet received arterial blood via one or more proper arterioles. These afferent vessels first divided in the peripheral zone of the islet consisting of A and D cells and later extended deeper to form a capillary network in the islet core consisting of B cells. Blood originating from this capillary network left the islet via efferent vessels. This microvascular pattern may favor the regulation by A and D cells over the secretory activity of B cells. The intralobular islets gave their efferent vessels to the capillary bed of the exocrine tissue of the lobule, thus forming an insulo-acinar portal system. When the lobule was relatively small in size, superfluent blood was led directly to veins via insulo-venous drainage vessels. The intralobular islets sometimes issued one or more long translobular portal vessels reaching adjacent lobules. The extralobular islets issued either insulovenous vessels draining to interlobular veins, or extralobular insulo-acinar portal vessels supplying adjacent lobules. PMID- 1295547 TI - Two components of the pineal organ in the mink (Mustela vison): their structural similarity to submammalian pineal complexes and calcification. AB - The pineal complex in the mink (Mustela vison) consists of a larger ventral and a smaller dorsal pineal. Both organs contain pinealocytes, neurons, glial cells, nerve fibers and synapses in an organization characteristic of nervous tissue. The cellular elements are arranged circularly around strait lumina. These lumina correspond to the photoreceptor spaces of submammalian pineals. A 9 + 0-type cilium marks the receptory pole of the pinealocytes which may form an inner segment-like dendrite terminal in the pineal lumina. The cilia correspond to outer segments which form photoreceptor membrane multiplications in the pineal of submammalians and in certain insectivorous and mustelid mammals (bat, hedgehog, ferret). Axonal processes of the pinealocytes contain synaptic ribbons and terminate on intrapineal neurons of both organs. This pattern represents a neural efferentation of the pineal nervous tissue. The axonal processes of pinealocytes also form neurohormonal endings which pierce the perivascular limiting glial membrane in the ventral as well as in the dorsal pineal. The upper pineal ("epipineal") of the mink may correspond to the parapineal, frontal, or parietal organs of submammalian pineal complexes. Both pineals are encapsulated by the meningeal tissue of the brain stem. Afferent vasomotor axons of the meninges innervate smooth muscle cells of pineal arterioles. There are corpora arenacea in the pineal arachnoid and in the pineal nervous tissue, primarily in the ventral pineal. The localization of calcium ions detected around the membrane of pineal cells by pyroantimonate cytochemistry suggests membrane activity as the source of the calcium ions. The accumulation of calcium by the pinealocytes may be due to their neurosensory character. The mink is the first animal described to have both intrapineal and meningeal concrements like the human pineal. PMID- 1295548 TI - Semiquantitative analysis of the effects of fixation and paraffin embedding on immunoreactivity of renal basement membranes to a monoclonal antibody against type IV collagen. AB - The effects of formalin fixation and paraffin embedding on the immunoreactivity of human kidney to a monoclonal anti-type IV collagen antibody (JK-199) were examined semiquantitatively by a modified enzyme-linked immunosorbent assay (ELISA). The intensity of immunoreactivity in paraffin sections of the tissue fixed overnight with 10% formalin was approximately 70% of that in frozen sections. Immunoreactivity reduced to this extent did not impair the specific staining of basement membranes. Paraffin sections of tissues fixed 2 days showed 50-60% of the reactivity in the frozen sections of the tissue fixed overnight; the basement membranes in Bowman's capsules were stained positively, but those in other sites were not. The paraffin sections of tissues fixed 7 or 14 days showed no specific immunostaining. The immunoreactivity for type IV collagen in the basement membranes was restored after treatment with pronase E. The immunoreactivity after the enzymatic treatment was about 150% of that in the frozen sections of the overnight fixed specimens. PMID- 1295549 TI - Localization of hyaluronic acid, chondroitin sulfate, and CD44 in rabbit cornea. AB - To demonstrate the localization of hyaluronic acid (HA) in rabbit cornea, the biotinylated HA-binding region, which specifically binds to the HA molecule, was applied to the tissue. Localization of chondroitin sulfate (CS) and CD44, a possible cell surface receptor for HA, were also examined by immunohistochemistry. The stainability of HA changed depending on the fixatives used. Reaction products for HA were distinctly detected in epithelial cells and stromal keratocytes, but faintly in the extracellular matrix of the stroma when unfixed cryosections were applied. No positive reaction was found in the endothelium, except that the positive deposits formed a continuous layer on the apical surface of the endothelium. Electron microscopy using samples fixed with 2% paraformaldehyde revealed gold particles indicating HA labeling the intercellular space of the epithelium and stromal extracellular matrix. No intracellular deposition was detected in epithelial cells, whereas the gold labeling was seen in vacuolar structures of stromal keratocytes. Immunodeposits for CS were intensely localized in the epithelium and stroma, and weakly in the endothelium. Immunoreactivity for CD44 was found in the epithelial, endothelial and stromal cells. In particular, immuno-deposits for CD44 were detected in basal parts of epithelial cells, while they were localized in the apical surface of endothelial cells. These results suggest that HA is synthesized in and secreted from epithelial and stromal cells of rabbit cornea, while the localization of HA in the apical surface of the endothelium is closely associated with that of CD44. Moreover, the presence of CS in corneal tissue may play a role in its transparency, as has been suggested for keratan sulfate and dermatan sulfate. PMID- 1295550 TI - Structure and distribution of the lymphatic vessels in the parietal pleura of the monkey as studied by enzyme-histochemistry and by light and electron microscopy. AB - The entire distribution of lymphatics in whole mount preparations of the Japanese monkey was studied using the enzyme-histochemical technique reported by KATO et al. (1990, 1991). In this staining, the lymphatic endothelium was colored dark brown by its positive 5'-nucleotidase activity, while most blood vessels (especially arterioles) were colored blue due to their positive alkaline phosphatase reaction. The whole mount preparations of the pleura treated enzyme histochemically clearly indicated the distribution, branching patterns and running courses of lymphatic vessels. They revealed numerous short blind-ending knobs which represented the initial portions of lymphatics. These knobs were seen near the surface of the parietal pleura along its entire extent. In the costal and diaphragmatic pleura, the lymphatics ran parallel to the intercostal muscle fibers, but perpendicular to the tendinous and muscular fibers of the diaphragm; they formed ladders, independent of the courses of blood vessels. In the mediastinal pleura, lymphatic vessels showed a tree-like branching accompanying blood vessels. Under the light microscope, toluidine-blue stained semithin sections revealed the initial part of lymphatics as a small irregularly outlined cavity (7-10 microns in diameter) surrounded by a dense connective tissue. This lymphatic dilation was sometimes located close to a thin mesothelial layer. Such a structure suggesting a "stoma" was seen near the attachment of the muscular diaphragm to the sternum and along the borders of the ribs. Transmission electron microscopy revealed an occasional interruption in the mesothelium. This stoma continued to a submesothelial cavity whose base comprised an attenuated endothelium of an extended lymphatic vessel. PMID- 1295551 TI - Three-dimensional changes in direction and interrelationships among enamel prisms in the dog tooth. AB - This study describes the three-dimensional features of enamel prisms and their arrangement in dog teeth. Tangential semithin sections of demineralized tooth germ were serially cut from the enamel surface to the enamel-dentin junction. Straight rows of enamel prisms parallel or perpendicular to the meridian were selected at the enamel-dentin junction; these prisms were reconstructed from micrographs with a personal computer. Near the enamel-dentin junction, the arrangement of enamel prisms appeared regular. Viewed from the enamel surface, the cut-ends of the enamel prisms that were parallel to the meridian at the enamel-dentin junction appeared as a sine curve, with 16 enamel prisms forming one period. The enamel prisms in a row perpendicular to the meridian were parallel to each other and deflected to the left or right from the enamel-dentin junction. Away from the enamel-dentin junction, the periodicity of the prisms gradually disappeared. The sine curve formed by the cut-ends of prisms in a row parallel to the meridian became irregular, and prisms in rows perpendicular to the meridian crossed each other. The semithin sections showed belt-like zones arranged perpendicular to the meridian. Each belt-like zone consisted of enamel prisms oriented in the same direction, those in neighboring zones being oriented in opposite directions. The disappearance of the regular arrangement of prisms was related to changes in their location in the belt-like zones. PMID- 1295552 TI - Electron microscope observations on the formation of primitive villi in rat small intestine with special reference to intercellular junctions. AB - Formation and fusion of intraepithelial cavities have long been considered an essential process in the histogenesis of the intestinal mucosa. By electron microscope observation of thin sections and freeze-fracture replicas of the small intestine of rat fetuses, we first demonstrated the initial steps in the formation of intraepithelial cavities: A focal tight junction (macula occludens) was formed in the abluminal part of the epithelium, after which the membrane of an intracellular cavity was fused with that of the focal tight junction to form an intercellular (intraepithelial) cavity enclosed by a zonula occludens. The present study also revealed that gap junctions appeared and enlarged simultaneously with the formation of primitive villi and differentiation of absorptive cells. These gap junctions gradually came to be confined in the epithelium of intervillous regions where proliferation and differentiation of epithelial cells took place. Absorptive cells in villi rarely had gap junctions. These results suggest that tight and gap junctions play important roles in the histogenesis of the intestinal mucosa, and in the proliferation and differentiation of epithelial cells. PMID- 1295553 TI - Immunoelectron microscopic observation of calcitonin gene-related peptide (CGRP) positive nerves in the dental pulp of rat molars. AB - The ultrastructure of nerves containing immunoreactivity for calcitonin gene related peptide (CGRP) was investigated in the dental pulp of rat molars. The immunoreactivity was recognized predominantly in unmyelinated nerve fibers, and sparsely in a few myelinated fibers. It was localized throughout the axoplasm, as well as in the large cored vesicles. Small clear vesicles and mitochondria were free of the immunoreaction. The CGRP-immunoreactive nerves were frequently observed to terminate, being devoid of Schwann cell investment, in the vicinity of blood vessels in the coronal pulp, suggesting that CGRP may be involved in the regulation of pulpal blood flow. Moreover, CGRP-immunoreactive axon terminals containing numerous small clear vesicles, a few large cored vesicles and mitochondria were recognized in contact with the cell bodies of odontoblasts and their processes in the dentinal tubules. Although specialized synaptic ultrastructures were not recognizable, a functional association of CGRP nerves and odontoblasts was suggested. Thus, CGRP in the dental pulp appears to have multiple functions, including vascular regulation and sensory transduction. PMID- 1295554 TI - A comparative study of myogenic cell invasion of the avian wing and leg bud. AB - The borders of myogenic cell invasion of avian wing and leg buds were determined using the interspecific grafting technique between quail and chick embryos. Distal parts of quail limb buds were grafted ectopically into the coelomic cavity of chick embryos. The presence or absence of skeletal muscle was investigated in histological sections of the reincubated grafts. A comparison between the borders of myogenic cell invasion of the wing and leg buds showed that the differences in the position of the distal most muscles in the adult avian limbs could be a consequence of the cranio-caudal sequence of development. PMID- 1295555 TI - A two-step alignment method for 3D computer-aided reconstruction based on fiducial markers and applied to mouse embryonic hearts. AB - An accurate three dimensional computer reconstruction of microscopic biological objects or distribution of molecules identified on serial sections must solve two major problems: 1) the alignment of sections using adequate extrinsic references (fiducial markers); 2) the impossibility of observing these references and the cellular or molecular structures in the microscope at the same magnification. To provide extrinsic references for objects embedded in soft media, we have modified and simplified the charcoal-paraffin method described by Langemeijer and Simons (1973). It consists of drilling three or four small holes into the paraffin block, sealing this block at the extremity of a glass holder and, from the other extremity of the holder attached to a rubber hose, aspirating a liquefied mixture of charcoal-paraffin to fill these cylindrical holes. An alignment procedure was developed using serial sections of mouse embryonic hearts with bromodeoxyuridine labelled DNA synthesizing cells. From each fourth section, two sets of contours have been drawn and digitized: 1) at low magnification (about 40x), embryo body wall, heart, neural tube and extrinsic reference marks (black dots); 2) at higher magnification (240-300x): heart contours alone (without extrinsic references, but with individual labelled cells). Different operations of the computer-aided alignment, as well as checking of results by inverse alignment, are described in detail. This two-step alignment method offers a practical, efficient compromise between: a) purely subjective alignment based only on tissular landmarks interpreted by the operator; b) ideal perfect alignment based not only on adequate references, but on computerized correction of section deformation, as well. PMID- 1295556 TI - Origin of primordial germ cells, as characterized by the presence of nuage, in embryos of the teleost fish Barbus conchonius. AB - The presence, location and morphology of cells containing nuage, an ultrastructural characteristic of primordial germ cells (PGCs), is described from the moment of first morphological recognition of PGC (around 100% epiboly) in embryos of the teleost fish Barbus conchonius. Thus characterized cells were studied in relation to their cellular contacts with somatic germ layer cells, possibly involved in the determination of PGCs. The results show that from the very moment that cells, likely to be PGCs, can be light microscopically identified with morphological and positional criteria (from 10 h post fertilization (p.f.) onwards), they contain nuage near the nuclear envelope, which is a strong indication of their PGC-identity. During the studied period (9 12 h and 24 h p.f.) nuage-containing cells seem to translocate from the mesoderm towards the yolk syncytial layer (YSL). These PGCs usually appear not to be directly connected with the YSL but to remain separated from the YSL by one or more endodermal extensions, at least up to 12 h p.f. Also at 24 h p.f. somatic cells separate the PGCs from the YSL. PMID- 1295557 TI - Morphological indications of secretion by uterine epithelial cells and changes in the ratio between acidic and basic uterine proteins during early pregnancy in Chinese Meishan pig. AB - In Chinese Meishan pig embryonic mortality appears relatively low compared to European breeds. Most of embryonic loss in pig is believed to take place during early pregnancy. It is of interest to know possible specific features associated with low mortality. Therefore, the ultrastructure of the endometrial epithelium of Meishan pig was studied between Days 4 and 12 of pregnancy, and compared with earlier results on Yorkshire/Dutch Landrace interbreed (Y/DL). Furthermore, total protein and the relative amounts of acidic and basic proteins were determined in the uterine flushings, and compared with earlier results on Dutch Landrace (DL). As holds for European breeds, uterine glandular and luminal epithelium have to be considered as functionally different cell populations. Their morphology differs and suggests the synthesis of different secretory products. The periods of secretion are not the same: the luminal epithelium shows signs of product release during the whole period studied, the glands deliver their secretions from Day 12. This is correlated with a sudden increase in total protein in uterine flushings. Between Days 4 and 12, the relative amount of acidic proteins decreases from 92% to 47% in DL and from 88% to 38% in Meishan, resulting in a shift from acidic protein dominance to a mild dominance of basic proteins in both breeds, but most prominent in Meishan. PMID- 1295558 TI - Geometrical differences between neck motoneurons located in the brainstem and spinal cord in the mallard Anas platyrhynchos L.; a Golgi study. AB - The dendrite geometry of neck motoneurons located in the upper cervical cord and lower brainstem of the mallard was studied in Golgi silver impregnated material. Measurements were obtained from camera lucida drawings and concerned the extent and orientation of dendritic trees. Dendrites were found to be oriented predominantly parallel to the sagittal plane, and projections were asymmetric in the dorso-ventral direction. Comparison between motoneurons located in the supraspinal nucleus of the brainstem and motoneurons in the ventral horn of the upper spinal cord showed that dendrites of motoneurons in the first cell group branch more often than those of neurons in the latter group. In addition, dendritic trees of ventral horn motoneurons preferentially project into the field dorsal to the cell body. PMID- 1295559 TI - The developmental mutants of Xenopus. AB - The 32 developmental mutants found in our laboratory have appeared in the course of the genetic analysis of adult Xenopus laevis issued from nuclear transfers, and of their progeny. These experiments originally were devised more than thirty years ago to test whether somatic nuclei had undergone irreversible changes during differentiation or whether they had remained totipotent. In the majority of cases, the mutations were carried by wild-caught imported frogs or their laboratory-bred progeny; however, the precise origin of several mutations has not been determined. The mutants have been subdivided into three classes: Maternal effect mutants. Three such mutants have been found; they affect the development of all the embryos from homozygous mothers independently of the genotype of the father. Developmental lethals. This class comprises 19 mutants, among which are included the previously called "autonomous lethals" caused by general metabolic defects that affect all parts of the embryos as well as the tissue- and organ specific lethals, in several of which death occurs as a direct consequence of the anomalies. Developmental non-lethals. These are 10 mutants, suffering from specific defects not essential for survival. In addition, nucleolar mutants as well as mutants found in different species of Xenopus and mutants of Xenopus laevis found in other laboratories are also mentioned. The last part consists of an alphabetical description of the mutant phenotypes including more detailed analyses which have been carried out on several of them. PMID- 1295560 TI - Effects of dentin proteins, transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP2) on the differentiation of odontoblast in vitro. AB - We have studied the effects of dentin proteins, of Transforming Growth Factor beta 1 (TGF beta 1) and Bone Morphogenetic Protein (BMP2) on the differentiation of odontoblasts in vitro. The total EDTA-soluble fraction of dentin proteins, prepared from rabbit incisors was further separated by chromatography on DEAE Cellulose and heparin-agarose columns. While the total EDTA-soluble fraction of dentin had no effect on cultured dental papillae, fractions retained on both columns were able to initiate functional differentiation of preodontoblasts of isolated day-17 first lower mouse molar dental papillae cultured in vitro. TGF beta 1 and BMP2, both stimulated the matrix secretion by dental papillae cells. TGF beta 1 and BMP2, combined with the inactive total EDTA-soluble fraction, stimulated odontoblast differentiation. An active fraction retained on DEAE Cellulose completely lost the inductive activity after incubation with a neutralizing anti-TGF beta antibody. These results demonstrate that a TGF beta like molecule present in dentin could interact with some component which acts as a modulator of its activity on the initiation of the cytological and functional differentiation of odontoblasts. PMID- 1295561 TI - Endogenous epidermal growth factor regulates the timing and pattern of embryonic mouse molar tooth morphogenesis. AB - The tooth organ provides a model for discrete patterns of morphogenesis over short periods of developmental time. Studies were designed to test the hypothesis that endogenous epidermal growth factor (EGF) functions to regulate multiple cusp molar tooth morphogenesis during embryonic mouse development. The relative levels of endogenous EGF and EGF receptor (EGFR) transcripts were determined in both enamel organ epithelia and dental ectomesenchyme by reverse transcription polymerase chain reaction (RT-PCR) assays. EGF and EGFR were localized by immunohistochemistry; both antigenic determinants were demonstrated on the same odontogenic cells in cultured tooth explants. To examine EGF-mediated signal transduction, cap stage mouse molar tooth organs (E16) were cultured in serumless, chemically-defined medium as either (i) controls, or supplemented with (ii) tryphostin (an EGF receptor kinase inhibitor), (iii) tyrphostin plus exogenous EGF, and (iv) exogenous EGF. Antisense oligodeoxynucleotide (ODN) strategy was used to investigate the functions of endogenous EGF employing (i) non-treated control, (ii) sense ODN control, (iii) antisense ODN, (iv) exogenous EGF, (v) sense ODN with exogenous EGF, and (vi) antisense ODN with exogenous EGF. Tyrphostin inhibited DNA synthesis and produced a significant decrease in the volume of the explants. These effects were recovered by addition of exogenous EGF. Antisense ODN inhibition resulted in abnormal cusp formations, decreased DNA synthesis, total DNA, RNA and protein content, and decreased stellate reticulum and tooth explant volumes. The decreased tooth size was not uniform, the most pronounced effect was in the stellate reticulum. This pattern of changes was not seen when antisense ODN treatment was supplemented with exogenous EGF. These results suggest that during cap stage of odontogenesis endogenous EGF acts to stimulate DNA synthesis, which increases the cell number of specific phenotypes within the enamel organ epithelia, and thereby regulates molar tooth morphogenesis. PMID- 1295563 TI - Altering the position of the first horizontal cleavage furrow of the amphibian (Xenopus) egg reduces embryonic survival. AB - The animal/vegetal cleavage ratio (AVCR), defined as the ratio of the height of the animal blastomere to the height of the Xenopus embryo at the 8 cell stage, can be shifted by placing embryos in novel gravitational fields: clinostating (microgravity simulation) increases AVCR, and centrifugation (hypergravity simulation) reduces AVCR. This report contributes to an understanding of the subcellular mechanism responsible for the furrow relocation and assesses its significance. Embryo inversion and D2O immersion were found to increase AVCR, and cold shock was found to reduce AVCR. Based on the additive or antagonistic effects of combined treatments, it is postulated that the primary cause of AVCR changes is an alteration in the distribution of yolk platelets and the rearrangement of microtubule arrays. Embryos with a decreased AVCR exhibited reduced survival in early developmental stages, indicating serious difficulties in cleavage, blastulation and/or gastrulation. Cold-shocked embryos with a reduced AVCR could be rescued by D2O pretreatment or clinostating, an observation which supports the notion that changes accompanying AVCR modifications represent the primary cause of the reduction in percent survival. PMID- 1295562 TI - Effects of retinoids on tooth morphogenesis and cytodifferentiations, in vitro. AB - The first embryonic lower mouse molar was used as a model system to investigate the effects of two retinoids, retinoic acid (RA) and a synthetic analogue, Ch55, on morphogenesis and cytodifferentiations in vitro. Exogenous retinoids were indispensable for morphogenesis of bud, cap and bell-stage molars in serum-free, chemically-defined, culture media. Transferrin and RA or transferrin and Ch55 acted synergistically in promoting morphogenesis from bud and cap-stage explants. Transferrin, per se, had no morphogenetic effect. Epithelial histogenesis, odontoblast functional differentiation and ameloblast polarization always occurred in RA-depleted explants. Comparison of the distributions of bromodeoxyuridine (BrdU) incorporation between explants cultured in the absence or presence of RA revealed that RA could modify the patterns of cell proliferation in the inner dental epithelium and dental mesenchyme. Inner dental epithelium cell proliferation is regulated by the dental mesenchyme through basement membrane-mediated interactions, and tooth morphogenesis is controlled by the dental mesenchyme. Laminin is a target molecule of retinoid action. Using a monospecific antibody, we immunolocalized laminin and/or structurally-related molecules sharing the laminin B chain in the embryonic dental mesenchyme and in the dental basement membrane and showed that RA could promote the synthesis or secretion of these molecules. Based on previous in situ hybridization data, it was speculated that CRABPs might regulate the effects of RA on embryonic dental cell proliferation. The fact that Ch55, a retinoid which does not bind to CRABPs, is 100 times more potent than RA in promoting tooth morphogenesis in vitro seems to rule out this hypothesis. On the other hand, the stage-specific inhibition of tooth morphogenesis by excess RA is consistent with the hypothesis that CRABPs might protect embryonic tissues against potentially teratogenic concentrations of free retinoids. PMID- 1295564 TI - Differentiation of endocrine myocardiocytes in the developing heart of the toad (Bufo arenarum Hensel). AB - The differentiation of endocrine myocardiocytes was investigated in the heart of developing toad Bufo arenarum Hensel, combining ultrastructural and immunocytochemical procedures. The distribution of immuno-reactive atrial natriuretic peptide (ANP) in the whole heart was appraised by light microscopy, applying biotin-streptavidin and immunofluorescence techniques. With the latter procedures ANP was first recognized at embryonic stage 22, in both atrium and ventricle. In the ensuing stages the ANP-reactivity became stronger in the atrium, while it became dimmer in the ventricle. At the end of the larval prometamorphic stage, atrial myocardiocytes acquired almost all the features of adult myoendocrine cells. At electron microscope level, small inclusions, about 110-120 nm in diameter, resembling secretory granules were found in myoendocrine cells beginning at embryonic stage 22. However, no immunogold labeling of ANP occurred until stage 25. The number of secretory granules diminished in the ventricles and increased in the atrium of the larval heart and at the end of the prometamorphic stage the atrial myoendocrine cells presented the ultrastructural characteristics of active secretory cells. The synthesis of ANP in larvae is enhanced at a critical period of development when the developing toad switches from an aquatic environment to terrestrial life. The cardiac hormones seem to play a key role in the regulation of the osmolarity of body fluids at this developmental stage. PMID- 1295565 TI - Changes in embryonic 8-cell nuclei transferred by means of cell fusion to mouse eggs. AB - Metaphase II and activated mouse oocytes were fused with 8-cell blastomeres, and morphological changes in the transferred nuclei were followed using light and electron microscopy. In metaphase II oocytes, blastomere nuclei underwent premature chromosome condensation (PCC) typical for S-phase nuclei: chromatin pulverization. Then an abortive spindle was formed without evident microtubule organizing centers. Blastomere chromosomes condensed to a lesser degree than meiotic chromosomes and lacked mature functional, trilaminar kinetochores. After parthenogenetic activation of these oocytes, blastomere chromosomes followed, in synchrony with oocyte chromatin, a similar route of changes (anaphase, telophase) and then reformed interphase nuclei of the pronuclear type. Remodeling of 8-cell nucleus thus occurred, but the integrity of the chromatin set was frequently disturbed by formation of micronuclei. If blastomere fusion with oocytes was done close to activation (either before or after parthenogenetic stimulation), the chances of remodeling of the nuclei decreased, because PCC was not regularly induced in all oocytes. In hybrids produced 60 min or later after oocyte activation, blastomere nuclei were maintained in interphase without any structural modifications. Multiple experiments in the mouse have shown that the nuclei from 8-cell stage transferred to enucleated oocytes and egg cells are not capable of substituting for pronuclear functions. Possible reasons for impaired functional reprogramming of 8-cell nucleus in the mouse are discussed in light of our present findings on the morphology of nuclei transferred before and after oocyte activation. PMID- 1295566 TI - Patterns of dystrophin expression in developing, adult and regenerating tail skeletal muscle of Amphibian urodeles. AB - The patterns of expression of dystrophin were investigated by indirect immunofluorescence and by immunoblotting in developing, adult and regenerating tail skeletal muscle of newts Pleurodeles waltl and Notophthalmus viridescens. In this study, a monoclonal antibody H-5A3 directed against the C-terminal region (residues 3357-3660) and a polyclonal antibody raised to the central domain (residues 1173-1738) of the chicken skeletal muscle dystrophin were used. Western blot analysis showed that these antibodies recognized a 400 kDa band of dystrophin (and may be of dystrophin-related protein) in the adult muscle tissues and in newt tail regenerates. During skeletal muscle differentiation or epimorphic regeneration (blastema), anti-dystrophin immunoreactivity gradually accumulated over the periphery of the myofibers. Dystrophin and laminin were first and concomitantly observed at the ends of the newly formed myotubes where they were anchored on connective tissue septa or bone processes by dystrophin rich myotendinous structures. It is noteworthy that neuromuscular junctions, which most probably also contain dystrophin, are established in urodeles near the ends of the myofibers as shown by histochemical localization of AChE activity or fluorescent bungarotoxin detection of AChRs. In the stump transition zone close to the tail amputation level where tissue regeneration of injured muscle fibers took place, dystrophin staining located on the cytoplasmic surface of myofibers progressively disappeared during the dedifferentiation process which seemed to occur during muscle regeneration as suggested by electron microscopy. Furthermore, double labeling experiments using anti-dystrophin and anti-laminin antibodies showed a good correlation between the remodeling processes of the muscle fiber basal lamina and the loss of dystrophin along the sarcolemma of damaged and presumably dedifferentiating muscle cells. PMID- 1295567 TI - Development of fetal thymocytes in organ culture: effect of corticosteroids. AB - Corticosteroids affect the development of fetal foregut-derived organs in which epithelial-mesenchymal interactions are associated with the developmental process. The thymus is one such organ and is profoundly sensitive to corticosteroids when mature. In this study corticosterone (CS) effects on fetal thymocyte development were investigated using a fetal thymus organ culture system which allows the growth, differentiation, and function of developing thymocytes to be monitored in vitro. CS inhibited, but did not block growth of fetal thymocytes, although the appearance of mature thymocytes was inhibited, similar to previously reported effects of interleukin 2 (IL2). CS enhanced the proportion of Mac1+, Ia+ and FcR+ cells and maintained high levels of IL2 receptor (IL2R) positive immature cells. Functional cytotoxic cells were detected in CS-treated organ cultures which expressed a Thy 1-, CD8- phenotype, atypical for thymus derived killer cells. While this cytotoxicity may be stimulated by CS, it could simply be due to a relative depletion of the main pool of thymocytes. These cytotoxic cells may have a role in directing apoptotic mechanisms occurring during thymocyte development. PMID- 1295568 TI - Cyclic changes of membrane conductivity in fertilized and activated eggs of teleost (Misgurnus fossilis) and their relation to the cell shape. AB - Oscillations of membrane ionic conductivity, with a period similar to cell cycle duration, were observed in fertilized and activated loach (Misgurnus fossilis) eggs. In cleaving eggs the decrease in conductivity coincided with mitosis. Synchronously with the oscillations of membrane conductivity in activated as well as in fertilized eggs, rhythmic changes in blastodisc shape occurred. The blastodisc rounded up during the period of increasing membrane conductivity and flattened while conductivity decreased. Scanning microscopy of fertilized and activated eggs revealed differences in the surface relief of rounded and flattened blastodiscs. PMID- 1295569 TI - Aminopeptidase activity levels during axonal and dendritic growth in the rat brain. AB - Brain aminopeptidase activity has been suggested as a candidate for the regulation and biotransformation of several neuropeptides. In this paper, changes in Lys- and Leu-aminopeptidase activities in rat brain hemispheres, cerebellum and medulla were examined in 1-, 3-, 5- and 7-days postnatal subjects. Aminopeptidase activities were studied by measuring the rate of hydrolysis of the artificial chromogenic substrates Lys- and Leu-2-naphthylamides (fluorimetrically detected in triplicate). Both enzyme activities show a decrease on the 3rd day of life followed by increases on the 5th and 7th day postbirth. It is suggested that these activities could play a part in the neurochemical changes that take place during axonal and dendritic growth in the rat brain. PMID- 1295570 TI - The metabolism of microinjected inositol trisphosphate in Xenopus oocytes. AB - Microinjection of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) into Xenopus oocytes evokes a complex physiological response composed of a transient and a slow depolarizing chloride current. We investigated the relationship between intracellular levels of Ins(1,4,5)P3 and the kinetics of the physiological response. Microinjected Ins(1,4,5)P3 was slowly degraded following first order kinetics of disappearance (t1/2 = 10 min). The degradation products were inositol bisphosphate (InsP2), inositol monophosphate (InsP) and inositol, as well as inositol tetrakisphosphate (InsP4). The rate of degradation of injected 3[H] Ins(1,4)P2 was much greater (t1/2 = 3 min), indicating that the conversion of InsP3 to InsP2 may be the rate-limiting step in the degradation process. The slow degradation of 3[H]-Ins(1,4,5)P3 was not a result of its conversion to Ins(1,3,4)P3 since no accumulation of InsP3 was observed within 10 min of microinjection of 3[H]-Ins(1,3,4,5)P4. Activation of protein kinase C (PK-C) with a phorbol ester transiently increased the rate of conversion of 3[H]-Ins(1,4,5)P3 to InsP2. This, however, did not significantly affect the overall kinetics of 3[H]-Ins(1,4,5)P3 disappearance. Our results indicate that the kinetics of Ins(1,4,5)P3 degradation do not correlate well with the termination of both the rapid and the slow components of the physiological response. The termination of the slow component of the response, however, may be related to the decay of Ins(1,4,5)P3-induced 45Ca efflux, which lasted about 10 min. PMID- 1295571 TI - Is physical working capacity determined by optimal magnesium concentration? AB - Two lines of research originated in the mid-seventies; one attempted to gauge the effect of strenuous effort on serum magnesium concentration (S-Mg) and the second, the effect of S-Mg on the indices of physical working capacity. In apparently healthy trained young Israeli men, long-term studies of the effect of strenuous effort on S-Mg showed that after a moderately strenuous effort (70 km forced march), there was a decrease of S-Mg which became statistically significant after 72 h, whereas after a severely strenuous effort (120 km forced march), the decrease was biphasic, being significant after 1 h, with a second fall after 72 h. In repeated experiments, the decrease of S-Mg was found to persist over time parallel 1. Since chronic lowering of S-Mg signifies a concomitant lowering of intracellular Mg content, these findings showed that Mg deficiency was a sequel to strenuous effort. Studies of the effect of S-Mg on the indices of physical working capacity showed that: (1) S-Mg determines the maximal voluntary muscle contraction force (MVC); (2) S-Mg affects, among other things, the maximal aerobic capacity (VO2max). The estimated daily Mg intake in the Israeli population is inadequate and a widely prevalent marginal to overt Mg deficiency is found in apparently healthy Israelis. It is proposed that an optimal physical working capacity in the Israeli population will be achieved only under conditions of Mg saturation of metabolism. Studies to validate this hypothesis are under progress. PMID- 1295572 TI - Sudden death of athletes: is it due to long-term changes in serum magnesium, lipids and blood sugar? AB - In young, apparently healthy, trained Israeli men, strenuous effort was reported to give rise to persistent magnesium (Mg) deficiency and a parallel long-term increase of cholesterol, triglycerides and blood sugar parallel 1-3. The relationship of Mg deficiency to the pathogenesis of cardiovascular disease has been increasingly documented during the last decade. Several authors have highlighted the phenomenon of sudden deaths in sport and have suggested that it is associated with cardiovascular disease. The association is discussed between Mg deficiency and increase of blood lipids and sugar, found as a sequel to strenuous effort, and cardiovascular morbidity and mortality risk reported in athletes. It is postulated that sudden death of athletes and other intensely training individuals during exertion, is mediated by the deleterious cardiovascular effects of persistent magnesium deficiency and the resultant hyperlipaemia and hyperglycaemia, which, as we have documented, follows strenuous effort. PMID- 1295573 TI - Urinary characteristics of the Cape porcupine Hystrix africaeaustralis: effects of photoperiod and temperature. AB - The Cape porcupine Hystrix africaeaustralis is a large (11-18 kg), nocturnal, burrowing and group-living rodent. It experiences a metabolic response to seasonal acclimatization and is a hind gut fermenter. Changes in the urinary electrolyte and free urinary catecholamine concentrations of Cape porcupines were related to combined changes of ambient temperature and photoperiod regime. Three groups, A) Ta = 25 degrees C, 12L:12D; B) Ta = 32 degrees C, 16L:8D; C) Ta = 10 degrees C, 8L:16D, were studied to assess the influence of seasonal acclimatization on urinary bicarbonate and catecholamine concentrations. Urine volume was significantly (p < 0.001) higher in group C than in the other two groups. In groups B and C urinary pH was above 7 and this was associated with high concentrations of HCO3-. The total amount of catecholamines was higher in groups B and C than in group A. It is apparent that seasonal acclimatization of the Cape porcupine is also reflected by these parameters. PMID- 1295574 TI - The mixed lipoxygenase/cyclooxygenase inhibitor SK&F 105809 reduces cerebral edema after closed head injury in rat. AB - Closed head injury in rats induces edema formation, which is indicated by a decrease in cerebral specific gravity and an increase in water content. We previously described the activation of the eicosanoid metabolic cascade, namely, activation of PLA2 and accumulation of products of both 5-lipoxygenase (5-LO) and cyclo-oxygenase (CO) in the same model of head injury. The present study was designed to determine the effect of a novel drug, SK&F 105809, a dual inhibitor of 5-LO and CO on cerebral edema formation after head injury in rats. Rats, under ether anesthesia, were subjected to sham operation or trauma induced by weight drop device impacting over the left calvarium. One group of traumatized rats received 0.9% saline and served as control and two other groups were treated with SK&F 105809, 20 or 30 mg/kg, i.p. immediately after the impact. In one group treatment was repeated additionally 2.5 h post-trauma. Four hours after trauma, rats were sacrificed and brain edema was evaluated. SK&F 105809 treated rats which received 30 mg/kg had significantly less brain edema, as measured by both gravimetry and water content, at 4 h after trauma. The lower dose, 20 mg/kg, had no effect. Our results suggest that treatment with a mixed 5-LO/CO inhibitor shortly after head injury will result in less brain edema and ultimately improved functional outcome. PMID- 1295575 TI - Different degree of ileal colonization by segmented, filamentous bacteria in two strains of mice. AB - Segmented, filamentous bacteria (SFBs) are autochthonous, apathogenic inhabitants of the ileum of various animal species. Outbred Swiss (Cpb:SE) mice have significantly higher degrees of SFB colonization than do inbred BALB/c mice. The present studies were carried out to identify determinants of this strain difference. In a cross-fostering experiment it was shown that SFB colonization of the pups is determined by the strain of the pups themselves rather than by the strain of the nursing dam. Thus, maternal effects may not be involved in SFB colonization. In a cross-infecting experiment using germ-free and SFB-positive animals of the two mouse strains, it was found that ileal SFB colonization is determined by host characteristics rather than by origin of the SFBs. Thus, SFBs that are specific for a given mouse strain may not exist in the two strains of mice. It is concluded that the mouse strain difference in SFB colonization is determined by host characteristics, which probably have a genetic basis. PMID- 1295576 TI - Changes in colonic mucins of germfree rats in response to the introduction of a "normal" rat microbial flora. Rat colonic mucin. AB - In order to determine the influence of bacterial colonization on amount and composition of colonic mucins, germfree male AS/Ztm rats were colonized with a rat specific intestinal flora for different times (2, 7, 14, 21, 28, 35, 120 days). The amount of colonic mucins was determined by gel filtration on Sepharose CL-4B; the relative amount of acidic mucins was calculated after ion exchange chromatography. In addition, cecal weight and dry matter of feces were monitored. While germfree and SPF rats revealed similar amounts of colonic mucins (7.0 vs. 7.2 mg mucin/300 g body weight), the initial phase of association was characterized by considerably decreasing values. After four weeks of association, the total amount of colonic mucins had almost equalized in the two groups. The amount of acidic mucins, having decreased during the first three weeks of colonization, rendered values comparable to the SPF mucins after four months of adaptation. Cecomegaly in germfree rats disappeared within the first two days, while solidification of the intestinal content occurred within four months. Mucin losses during initial phase of association are attributed 1. to the disappearance of the cecal mucin pool, and 2. to the mucin degrading activity of some bacterial strains known to be present in the intestinal flora. Further development is conducted by a stimulation of mucin secretion, described to follow the colonization. The initially increased secretion of neutral mucins is attributed to a pronounced release of immature mucin glycoproteins, while the shift to more acidic mucins is considered to result from stimulated secretion as well as from a selective bacterial degradation of neutral mucin components. PMID- 1295577 TI - Oligonucleotide fingerprinting in Xiphophorus melanoma. Detection of a melanoma associated DNA modification. AB - Oligonucleotide fingerprints have been generated from fish melanomas and were compared to the constitutional multilocus patterns from normal brain DNA of the same individual. In 3 out of 8 cases additional bands were observed in the tumor DNA. This phenomenon can only be explained satisfactorily by so far unknown modes of DNA modification. PMID- 1295578 TI - Life expectancy, its relation to sexual activity and body weight in male inbred mice. AB - Body weight of male mice of five inbred strains caged in groups of five was determined three times between the ages of 80 and 100 days, representing the individual fully grown body weight. Sexual activity of each mouse (number of ejaculations and intromissions) was estimated under competitive conditions between the ages of 120 and 150 days in eleven repetitions. Within all inbred strains only about half of the males displayed sexual activity when confronted with an estric female. The other do not. The animals remained in their cage groups until natural death after 727 +/- 215 days (C57BL/6), 638 +/- 260 days (BALB/c), 630 +/- 187 days (CBA), 560 +/- 230 days (DBA/2) and 317 +/- 62 (AKR) days. Only amongst the sexually active animals did individual life span correlate with the number of ejaculations. This was seen in C57BL/6, CBA and DBA/2. Particularly sexually successful animals, carrying out the most ejaculations, live 10-20% longer than their (subdominant) competitors displaying less sexual success. Sexually inactive males (characterised by no ejaculations and less other sexual activities) show that this characteristic of their personalities imposes no limitation upon their life expectancy. Fully grown body weight and the individual life span correlates within the strains DBA/2, C57BL/6 and BALB/c. Medium-sized animals have a greater life expectancy than small or large ones. PMID- 1295579 TI - Examination of brown adipose tissue thermogenesis of glutamate-induced obese rats by differential temperature measurements. AB - Differential temperature measurement between interscapular brown adipose tissue (BAT, Tbat), rectum (Trect) and a subcutaneous point in the back left of the vertebral column (Tsc) was useful for examination of BAT-thermogenesis in glutamate-induced obese Wistar-rats. Positive temperature gradients Tbat-Tsc pointed to a basal BAT-thermogenesis, whereas negative temperature gradients Tbat Trect did not indicate that heat production in lean and obese rats. One may conclude from this, that inclusion of subcutaneous points outside the BAT improves sensitivity of differential temperature measurements for BAT thermogenesis. Basal temperatures Tbat, Trect and Tsc were reduced in obese rats compared to lean rats, although thermoinsulation of obese rats is improved on account of their high fat content. This points to a diminished heat production in obese rats. Cold exposure at 4 degrees C elicited an increase of temperature gradients Tbat-Trect in lean as well as in obese rats, with positive values found only in lean rats. However, positive values Tbat-Tsc were calculated for both groups. Increases were noted only in lean rats. Injection of noradrenaline (0.5 mg/kg i.m.) was followed by positive temperature gradients Tbat-Trect and increased positive values for Tbat-Tsc, pointing to a remarkable activation of BAT-thermogenesis in lean and obese rats. These findings confirm, that glutamate induced obese rats preserved the ability to activate BAT-thermogenesis. There were, however, hints of reduced heat production in BAT of obese rats, thus contributing to obesity despite normophagia. PMID- 1295580 TI - [Acute early rejection in renal transplantation]. AB - The incidence of early acute rejection (first two months after surgery) was evaluated in a group of 150 kidney transplants, receptors, who were followed for more than three months. Ninety nine were transplanted with kidney from a cadaver donor and 51 with living donor. One hundred forty two patients were treated with triple immunosuppression therapy (cyclosporine, prednisone and azathioprine). The incidence of early acute rejection was significantly higher in cadaver kidney receptors (34% vs 19.6%, p = 0.04. Fisher exact test). However, early rejection did not have demonstrable influence in graft or patient survival or in the follow up graft function. Graft and patient survival were not affected by the severity of the rejection episode. PMID- 1295582 TI - [Excellence in scientific research]. PMID- 1295581 TI - [Retrospective diagnosis of a sample of patients discharged with a diagnosis of schizophrenia]. AB - A retrospective diagnosis was obtained from a sample of 300 patients discharged from the Psychiatric Hospital of Maracaibo (Venezuela), with the clinical diagnosis of schizophrenia. These medical records were evaluated under DSM-III criteria, by two psychiatrists using structured formats. We found that 46.3% of the patients met the criteria corresponding to the schizophrenic disorder; from the remaining 53.6%, 19.6% did not have enough information to be included in this category, and 34.6% was classified under other psychiatric disorders. Of the patients with schizophrenic disorders, 61.2% were male, single, and Venezuelan citizens; 84.9% began their clinical manifestations during the second or third decade of their lives; 89.9% received education. The predominant symptomatology was impairment in social relations (93.5%), deterioration in hygiene and self- care (92.5%), impairment in functioning (87.1%), illogical thinking (86.3%), with predominant persecutory delusions, auditory hallucinations, dialogue hallucinations (84.6%), grandiose delusions (48.2%), and personal experiences of corporeal changes (45.3%). Affective symptomatology were present in all patients and the predominant subtype was the paranoid, that was observed in 80.6% of the cases. Positive signs of this disease in family history were present in 41 percent of the cases. Our findings confirm the necessity to unify criteria concerning the diagnosis of mental disorders, as it became evident that the variability in diagnosis, makes more difficult the psychiatric research in our country. PMID- 1295583 TI - Observation on a human intentional poisoning case by the organophosphorus insecticide fenthion. AB - A case of acute poisoning by oral ingestion of fenthion is reported. Plasma cholinesterase activity and fenthion whole blood concentration were thoroughly evaluated during the therapeutic intervention that consisted in administration of atropine, toxogonine and fresh plasma. Correlation studies between clinical signs, cholinesterase activity and fenthion levels revealed that pChE activity was not as helpful as the patient's clinical status in determining when the atropine infusion could be stopped. Moreover pChE was also useless in signaling sudden relapses. It is concluded, based on this case, that supportive care combined with antidotal therapy remains the cornerstone of treatment specially in severe acute poisoning cases. PMID- 1295584 TI - [Thoracic ectopic kidney. Report of a case]. AB - We describe a 23 months old boy who presented a clinical picture of bronchial hyperreactivity and a tumoral intrathoracic mass in a plain thorax X-ray, receiving for these reasons, antibiotic therapy during 30 days. Intravenous pyelography and ultrasonography revealed the presence of an ectopic intrathoracic kidney. Since this renal anomaly is usually asymptomatic and do not requires treatment, it is necessary to suspect this abnormality whenever an intrathoracic mass is found. PMID- 1295585 TI - [The distribution of mutans streptococci and lactobacilli depending on the caries prevalence in 11- to 12-year-old children]. AB - 20 Korean children, aged 11 to 12 years, participated in this study with the aim to compare the microbial composition of plaque samples in order to estimate, which genera (lactobacilli, streptococci) or species are associated with coronal caries. Significant differences in the microbial composition of plaque samples between children with healthy and carious dentitions were found. S. mutans (c, e, f) was dominating under Mutans-streptococci. PMID- 1295586 TI - [The synthesis of collagenous and noncollagenous proteins by cells from the periodontium]. AB - Synthesis of collagenous and noncollagenous proteins by cells originating from the alveolar bone (AB-cells) and from the periodontal ligament (PDL-cells) of 8 minipigs was analyzed in primary cell cultures. Incorporation of 3H-proline into proteins recovered from cell extracts showed, that 13.7% of protein synthesized by AB-cells and 8.0% of protein synthesized by PDL-cells were collagens. In both cell lines relative amounts of collagens synthesized decreased significantly on subculturing (AB-cells: 9.3%, PDL-cells: 6.0%). Preincubation of 2nd subculture AB-cells with beta-glycerophosphate had no significant effect on collagen synthesis. Considering the fact that relative amounts of collagen recovered from cell extracts represent only 10-20% of collagen recovered from whole culture (i.e. cells and culture medium), we suggest that collagen synthesis is an important component of in vitro-protein synthesis of cells originating from the alveolar bone and the periodontal ligament. PMID- 1295587 TI - [Reattachment after gingivoplasty--the initial results of an experimental animal histological study]. PMID- 1295588 TI - [In-vitro research on the marginal adaptation of composites with the use of different dentin adhesives]. AB - The aim of this investigation was the check and evaluation of 7 various dentin adhesives regarding their influence on the connection between dentin resp. enamel and composite filling. For that cylindrical cavities in dental crowns (enamel cavities) and roots (dentin cavities) were prepared and treated with dentin adhesives and composite materials. One part of the test teeth was subjected to loads storage in aqueous solution and thermocycling. The marginal adaptation of the composite filling was checked by means of the dye penetration test. The evaluation was made after cutting the teeth in the stereo microscope TECHNIVAL 2 (Carl Zeiss Jena) at 16-resp. 25 magnifications and defined criteria. The fillings in cavities bound by enamel exhibited a very good marginal adaptation of the composite. The location of the dentin cavity (crown or root dentin) had no significant influence on the fitting of the filling. A clear penetration of dye could be observed with the fillings in the dentin with and without adhesives, which considerably intensified after thermocycling. Best results with regard to the marginal adaptation were obtained with Scotchbond 2, Mirage-Bond and Cavex Clearfil-Newbond. A restoration without a marginal gap was not possible. PMID- 1295589 TI - [Legionellae in dental units--a hygienic risk?]. AB - Water samples were collected from the hot water systems and from dental units in 12 dental offices of Dresden and cultured for legionellae. From seven (58%) hot water supplies and from dental units in 6 (50%) offices legionellae could be isolated. To asses the hygienic risk for dental staff we studied the prevalence of antibodies against Legionellae in serum samples of 113 dentists, 105 dental nurses and 17 dental technicians. In comparison with a control group of healthy people (132 women, 161 men, 20-80 years) living in the Dresden area, dentists have had a higher prevalence of antibodies against legionellae. In a lesser degree this was the case in sera of dental nurses and dental technicians. There were substantially differences in the prevalence of legionellae antibodies in different facilities. The incidence of positive antibody titers rises with the duration of occupation. None of the dentists with high antibody titers have had a story of pneumonia in their history of life. Thus a higher risk for dentists to acquire legionnaires' disease during their professional duty cannot be established. PMID- 1295590 TI - [Oral leukoplakias--a histopathological and retrospective study]. AB - In a retrospective study 85 patients of our department with clinical oral leukoplakia occurring between 1980 and 1985 were checked histologically and reclassified. Compared to other studies and unusual high malignant transformation rate (14.1%) was found which seemed to be depended on the high rate of radiated patients. Four of twelve patients were healed due to early diagnosis and radical surgery performed consecutively. Using these data as a basis the different courses and therapies are demonstrated. PMID- 1295591 TI - [The treatment results in the differential therapy of mouth carcinomas. A retrospective study of the patient population of the Oral Surgery Department (1978-1986) of the University of Gottingen]. AB - In a retrospective observational study on malignomas of the oral and maxillofacial region a data material of 157 patients has been analyzed. Results of the therapy and the course of disease are presented. The average delay between the appearance of the first symptom respectively the beginning of a therapy and the treatment in a specialized department for maxillofacial surgery runs up to 4.3 month and 2.8 month respectively. This dissatisfying situation is corroborated by the results for TNM categories with more advanced tumors. Only 16.6% of the patients belong to the T1 category, 42% to the T2 category and 35.7% to the T3 category. In 30.5% of cases tumor cells are found in cervical lymph nodes. Correlations between the size and the localisation of the primary tumor and metastases are obviously. The results of treatment are presented in form of survival curves and curves for times of no recurrence. There is no advantage in a combination of chemotherapy and surgery instead of single surgical therapy. In cases of more advanced tumors in T2 and T3 category there is no recurrence after 2 years in 70% of surgical treatment and in 69% of combined surgical treatment and chemotherapy. The censored estimated survival rate after 5 years in cases of surgical treatment comes to 63%, in cases of combined therapy to 62%. The consistent radical neck dissection is of distinctive signification. Recurrencies in the neck dissection region appear in 8.2% of patients. PMID- 1295592 TI - [The gingival margin incision as the surgical approach in cleft jaw osteoplasty- the technic, the healing process and postoperative complications]. AB - Marginal incision became a common surgical approach in periodontal surgery because of its good healing results. Since 1983 we use this incision for bone grafting in cleft palate patients. Out of 120 cleft palate patients which had marginal incision for bone grafting, 9 developed local dehiscence, 3 times in combination with partial loss of the cancellous bone transplant. We saw one total loss of the transplant caused by infection. The good results of primary wound healing, the absence of horizontal scars and the possibility of mobilisation of epithelium from the cleft region to cover the transplant with mucosa from the alveolar process are the advantages of this procedure. PMID- 1295593 TI - [The teeth and old age in the literature and art of Greco-Roman antiquity]. PMID- 1295595 TI - Regulatory mode of the pac gene expression. AB - 1.65kb HindIII-BgIII DNA fragment containing pac operator was cloned from plasmid pPA4 to pBR322 at HindIII-BamHI sites, the resultant plasmid pPA41 was transformed into E. coli D816 carrying an intact pac operon on its chromosome, then the effect of operator titration was estimated. It was found that the penicillin acylase activity in E. coli D816 (pPA41) cells was higher than that of in E. coli D816 cells. The operators on high copy number plasmid pPA41 competed for the regulatory proteins with the single copy operator on the chromosomal pac operon, thus the expression of the pac gene was enhanced, because the free regulatory proteins were decreased by operator titration. The results of RNA-DNA hybridization showed that the cellular pac mRNA concentration was parallel to the penicillin acylase activity, and the pac mRNA in E. coli D816 (pPA41) cells was much higher than that of in E. coli D816 cells. These results indicated that the expression of pac gene was negatively controlled at transcriptional level. PMID- 1295594 TI - Cloning and nucleotide sequence of chloroplast psaA gene from sorghum. AB - The 6.7 kb EcoRI fragment containing the sorghum chloroplast psaA gene was cloned. The restriction endonuclease map and the nucleotide sequence were determined. The length of the determined nucleotide sequence was 3080 bp, of which the psaA coding sequence was 2253 bp, which encoded a polypeptide of 750 amino acids with a estimated molecular weight of 83000. The homologies of this psaA gene of sorghum with those of maize, rice and spinach were 99.4%, 96.3% and 89.4%, respectively, and the homologies of the deduced polypeptide sequences were 99.3%, 98.0% and 95.7%, respectively. We found that a difference in the profiles of the hydrophobic distribution of P700 apoproteins existed between C4 and C3 plants due to a change occurred at the 493th amino acid (C4 plants: Gly; C3 plants: Arg or Ser). PMID- 1295596 TI - Cloning, characterization and partial sequence analysis of the 5'-flanking region of bovine alpha-sl casein gene. AB - We have isolated a clone from a EMBL3 constructed bovine genomic library using a PCR-generated DNA fragment as a probe covering-660bp to + 158 bp of boving alpha sl casein gene. The results obtained from hybridization assay, restriction endonucleases map and partial DNA sequence analysis indicated that the cloned fragment spanned 5.7kb of the first part of the gene and 8.0 kb of its upstream flanking region. Some divergent restriction endonuclease recognition sites and a few mutations and deletions were found in exons, introns and 5'-flanking region of the gene we cloned when compared with the PCR-generated fragment and those which had been published [6,10]. All the deletions occurred at repeat sequences. PMID- 1295597 TI - Utilization of the protoplast fusion technique to explore directional altering lincomycin producing microorganism. AB - Interspecific protoplast fusion between Streptomyces lincolnensis var. lincolnensis (LM gamma, CTC gamma, producing lincomycin) protoplast and Streptomyces aureofaciens (LM gamma, CTC gamma, producing chlorotetracycline) protpolast which had been treated with UV radiation 40 min for inactivation was performed with PEG 6000, the fusants were obtained by directly selecting from the regeneration plates containing CTC 50 micrograms/ml, the fusion frequency was about 9.05 x 10(-5). From many fusants, only 4 stable recombinants were obtained. These species produced antibiotics which are different from lincomycin and chlorotetracycline. Preliminary identification of the antibiotic synthesized by one of the recombinants suggests that its basic structure might be similar to that of lincomycin. The fermentation product of recombinant No. 2 showed new chromatographic spot which is similar to that of clindamycin. Though the products remain to be identified further, this strategy seems to be worthy of exploring for screening new antibiotics. PMID- 1295598 TI - A perfusion system for high productivity of monoclonal antibody by hybridoma cells in a CelliGen bioreactor. AB - DA4-4 (ATCC HB57) is a shear sensitive mouse-mouse hybridoma cell, producing an IgG1 monoclonal antibody against human IgM. It was grown successfully in a perfusion propagation system consisting of a 1.5 CelliGen stirred bioreactor and a hollow fiber cartridge. CelliGen system produced low shear force and cells could grow well at high agitation of 150 rpm. The culture was maintained for 40 days and cell number reached 20 x 10(6)/ml. Maximal monoclonal antibody concentration was 4.75 mg/ml. This system produced about 1.0 g of antibody every day at its peaks. PMID- 1295599 TI - Purification and partial characterization of an antibacterial protein LCIII. AB - Total proteins were precipitated by (NH4)2SO4 from the overnight culture supernatant of antagonistic bacterium Bacillus subtilis A014, applied to CM52 column and separated into three main peaks. The preparation of peak III showed to inhibit specifically the growth of rice bacterial blight pathogen Xanthomonas compestris pv. oryzea was further purified with Mono S column on FPLC and named antibacterial protein LCIII. The molecular weight of this protein is 26915Da, pI = 9.12. Analysis of amino acid composition was revealed to be rich in glycine, threonine and serine, and devoid of proline. Twenty-eight amino acids of N terminal were sequenced by the Edman degradation and computer analysis of this partial sequence showed that antibacterial protein LCIII is a novel one. PMID- 1295600 TI - Studies on kinetic model of vitamin C two-step fermentation process. AB - This paper aims at analyzing the bioconversion process from L-sorbose to 2-Keto-L gulonic acid with the aid of the growth factor assumption. Fermentation mechanism is discussed after making necessary simplifications. A model is established for this second step fermentation process. Nonlinear optimization together with Runge Kutta method, are used to obtain model parameters. Results of computer simulation agree with experimental data to show the reliability of the kinetic model. PMID- 1295601 TI - Estimation for model parameters of batch fermentation kinetics. AB - Based on the widely accepted mathematical model of fermentation kinetics, an analytical solution is deduced in this paper. To describe the feature of batch fermentation, the parameters of the fermentation kinetics in the analytical solution (i.e., mumax, Ks, beta, YG, YP, and m) are estimated at one strike with POWELL optimization algorithm coded in FORTRAN-77. The experimental data in the example is quoted from a batch lysine fermentation process using Corynebacterium glutamicum. The result shows that: 1) the calculated values of the mathematical model agree very well with the experimental data; 2) the synthesis rate of lysine depends on both the growth rate and the concentration of the biomass. PMID- 1295602 TI - Screening of bacterial strains producing maltotetraose-forming amylase and the conditions for enzyme production. AB - The authors isolated 1380 bacterial strains from 290 soil samples collected in China and 490 strains were received from other research teams in this institute. By screening 707 strains showed starch-hydrolyzing activity. By further screening and paper chromatographic test, three strains with maltotetraose as the major product were obtained. The maltotetraose was further confirmed by treatment with beta-amylase splitting to maltose and with glucoamylase to glucose. The most promising strain was 537.1, which produced maltotetraose about 90% (w/w) in the starch hydrolysate. While the other two strains produced maltose and maltotriose besides maltotetraose. Strain 537.1 was tentatively identified as Alcaligenes sp. The optimum conditions for enzyme production were as follows: medium composition: 1.5% maltose; 0.5% peptone with initial pH of 7.0-7.5; cultured at 27-28 degrees C for 48 hours on rotary shaker. The culture supernatant of the strain 537.1 can hydrolyze starch and different kinds of cereal flour with a high yield of maltotetraose in the hydrolysate. PMID- 1295604 TI - The electron microscope comparative study of the thyroidian cell in Graves' disease and of the normal human thyroidian cell. AB - The comparative study of the thyroidian cell in Graves' disease and of the normal human thyroidian cell allows interesting findings about the changes of the thyroidian tissue in abnormal conditions. Histologically in Graves' disease appears a diffuse and general hyperplasic and hypertrophic process, affecting all the component parts of the thyroid cell. The thyroid cell appears to be high, columnar, with a retained nucleus/cytoplasm ratio. The cellular apical pole is covered by a thin plasmatic membrane with many microvilli. The cytoplasm has a foamy, distended aspect, established by the general hypertrophic and hyperplasic process of the cell constituents, respecting the normal arrangement of the normal cell. In electron microscopic images mitochondrias look like round and very distended formations with evident christae and a twofold membrane. The vesicles of rough endoplasmic reticulum are very closed to the mitochondrias and the Golgi apparatus represented by vesicles and bags and are situated around the nucleus. The secretion granules are abundant at the apical pole, the vesicular bodies are bigger and very numerous the nucleus has big amounts of euchromatin. This aspect is very similar to the exagerated function of the thyroid cell in Graves' disease. PMID- 1295603 TI - Dyes as teratogens. AB - The main fats and problems of the role of dyes in prenatal pathology are reviewed. The first section deals with the practical aspects related to teratological screening of industrial dyes (including also the results obtained in this laboratory). In the second section, various aspects of azo-dye teratogenesis are largely discussed, including also the experimental contributions of this laboratory. Concluding remarks are made with respect to the importance and to the perspectives of this field of research. PMID- 1295605 TI - Urethral and neobladder cytologic survey in patients with total cystectomy. AB - Fourteen patients with total cystectomy and sigmoidian ureterostomy, 10 with cutaneous ureterostomy and 6 with substitution bladder were studied from the cytologic point of view; from all patients samples of voided urine, urethral and neobladder washing were taken and smears stained with blue polychrom-tanin Dragan; the smears which belong to the last group were cytochemically investigated, too. From morphohistochemical point of view biopsies taken from cases with recurrences and one case with substitution bladder which died in the 10th day after surgery were studied. The cytologic study revealed two recurrences: one urethral and one at the pelvis level at 18 and respectively 4 months from total cystectomy, both being transitional cell carcinoma. Cytologic and histochemical aspects of the intestinal wall used as neobladder are described, revealing epithelial modifications and chronic inflammatory infiltrate with marked decrease of mucous synthesis. The importance of urinary cytology in oncologic survey of these patients is discussed. PMID- 1295606 TI - Histochemical study on the activity of some oxidative and hydrolytic enzymes in the normal human endometrium blood vessels and at various intervals after applying the intra uterine contraceptive device. AB - The paper intends to study the cytoenzymological modifications of the human endometrium blood vessels after applying the intrauterine contraceptive device for a long period of time. The results were different according to the: type of the enzyme-ATP-ase, Lactatdehydrogenase, Leucineaminopeptidase, NADH2-citochrome c-reductase, the components of the blood vessel wall (intima, media, adventitia), the blood vessel diameter, the hormonal cyclic stage. PMID- 1295607 TI - Morphometric study of cell populations in primary breast tumors and their lymph node metastases. AB - The study of nuclear parameters (long and short nuclear axes, nuclear axes ratio, nuclear area) revealed differences both between the primary breast tumors and their lymph node metastases and between the lymph nodes isolated from the same axilla. The results are discussed in terms of tumor progression. PMID- 1295609 TI - Multiple inverted papilloma of the urinary bladder associated with glandular metaplasia of colic type. A case report. AB - A case of inverted papilloma of the urinary bladder associated with glandular metaplasia is presented. A bladder urothelial carcinoma was suspected after clinic and endoscopic findings, but the diagnosis was established only on histological picture. Morphological and histochemical peculiarities of the lesions are described, considering the case being the first with such an association-according to our knowledge. The malignant potential of inverted papilloma and glandular metaplasia are discussed. PMID- 1295608 TI - Cytomorphological, ultrastructural and immunological characteristics of the ovialsyn fluid in seropositive rheumatoid arthritis. AB - Experiments have been performed on 15 samples of synovial fluid (SF) from patients with seropositive rheumatoid arthritis (RA) (Latex 1/280 and Waaler Rose 1/1024) versus 10 SF samples from patients with hydroarthrosis, used as control. By cytomorphologic studies, we determined the cellularity, ragocytosis and synoviocytogram of the SF cellular pellet and found out that rheumatoid SF is characterized by cytosis (9953/mm3), ragocytosis (70%) and polynucleosis (73%) whereas hydroarthrotic SF is characterized by lymphocytosis (54.6%). Ultrastructurally, rheumatoid SF ragocytes present numerous intracytoplasmic inclusions and phagolysosomes, a fact that certainly evidences an endocytotic activity. At the level degenerative of PMN cells, (6%), the experiments evidenced the presence of some lysis cytoplasmic plateau associated with the absence of cellular organelles, as well as an alteration of the granulofibrillar structure of the nucleus. We also noticed cellular debris consisting of partially destroyed cellular organelles. By immunologic studies we obtained seric pathologic values for CIC (mean = 108.05 U), IgM (mean = 420 Ul/ml), IgG (mean = 355 Ul/ml), anti DNA antibodies (mean = 405 U) and anti collagen II antibodies (mean = 558 U). As regards the seric complement activity of C1q and C3 fractions, it was higher (mean = 18.87 mg% and mean = 109.94 mg%, respectively) than in the SF (mean = 5.78mg% and mean = 30.83 mg%, respectively). Corroborating the cytomorphological, ultrastructural and immunological data, we could better explain the lesional types examined and emphasize the importance of the immunomorphological changes in RA diagnosis. PMID- 1295611 TI - [A comparison of the morphological aspects of the pregnant and non-pregnant sheep myometrium]. PMID- 1295610 TI - Kawasaki disease in an infant with cystic fibrosis. AB - The authors report a case of a 3-month-old infant with a very rare association: cystic fibrosis and Kawasaki disease. The clinical picture is atypical but cardiovascular signs consist of cardiomegaly, sick sinus syndrome and Q waves in D II, D III and AVF. The diagnosis is confirmed by the pathological changes found at the postmortem examination. The patient is the first case of Kawasaki disease reported in Romania. PMID- 1295612 TI - Dynamics of Golgi impregnation in neurons. AB - This paper describes the early stages of impregnation by the Golgi rapid method in sections and blocks of brain tissue. Aldehyde-fixed and potassium dichromate treated sections of cerebral cortex were placed on glass slides and coverslipped. The dichromate solution was then replaced by a silver nitrate solution, and events taking place in the section were monitored and time-lapse recorded until the impregnation was interrupted and the sections subsequently prepared for electron microscopy. The tissue blocks, fixed and chromated in the same way, were placed into a silver nitrate solution for 30 min to 24 h and the progress of impregnation compared with the results obtained in the sections on the glass slides. Two basic modes of impregnation were observed, apparently in direct relation to the process of crystallization of silver chromate: crystals of silver chromate growing directly from the surface of the tissue into the nerve cell via its transected plasma membranes, and microcrystalline precipitate of silver chromate spreading into the nerve cell from nucleation centres dispersed in the tissue. The precipitate grows inside the cell as in a preformed channel until the cell has been filled. If the nucleation begins extracellularly, the precipitate extends into the narrow intercellular gaps. Electron microscopy showed that the crystalline precipitate consisted of multilamellar formations containing dense coalesced granules that did not cross plasma or endocellular membrane boundaries. PMID- 1295613 TI - Techniques for converting Golgi precipitate in CNS neurons into stable electron microscopic markers. AB - Direct electron microscopy of nervous tissue stained with the Golgi impregnation method is unsatisfactory because the cytoplasm of the cell bodies and processes of the impregnated neurons are completely filled with a compact precipitate of electron dense silver chromate. This precipitate entirely obscures the cytological details of the impregnated neurons. Because of its solidity and instability in aqueous solutions, the silver chromate is also a source of inconvenience during the preparation of the ultrathin sections. This review summarizes methods that have been developed with the aim of replacing the Golgi precipitate in CNS neurons with a more convenient electron dense material--for example, heavy metal salts or metallic particles. Conversion of the precipitate into a stable electron dense marker is done before the material is embedded for electron microscopy. The methods include lead, gold, and bromide substitution, treatment with ammonia, direct chemical reduction into metallic silver, and photoreduction of the silver chromate into silver through irradiation with ultraviolet light. PMID- 1295614 TI - Electron microscopy of Golgi-impregnated interneurons: notes on the intrinsic connectivity of the cerebral cortex. AB - The Golgi-electron microscope technique has opened new avenues to explore the synaptic organization of the brain. In this article, we shall discuss basic methodological principles necessary to analyze axonal arborizations with this combined technique. To illustrate the applications of the method, we shall review the forms and distribution of the synapses in which the axonal arborizations of local cortical interneurons engage. PMID- 1295616 TI - A holder for critical point drying of large numbers of EM-grids. PMID- 1295615 TI - Application of the Golgi/electron microscopy technique for cell identification in immunocytochemical, retrograde labeling, and developmental studies of hippocampal neurons. AB - In this study the Golgi/electron microscopy (EM) technique has been used for an analysis of the fine structure, specific synaptic connections, and differentiation of neurons in the hippocampus and fascia dentata of rodents. In a first series of experiments the specific synaptic contacts formed between cholinergic terminals and identified hippocampal neurons were studied. By means of a variant of the section Golgi impregnation procedure, Vibratome sections immunostained for choline acetyltransferase, the acetylcholine-synthesizing enzyme, were Golgi-impregnated in order to identify the target neurons of cholinergic terminals in the hippocampus. It could be shown with this combined approach that cholinergic septohippocampal fibers form a variety of synapses with different target structures of the Golgi-impregnated and gold-toned hippocampal neurons. In this report cholinergic synapses on the heads of small spines, the necks of large complex spines, dendritic shafts, and cell bodies of identified dentate granule cells are described. The variety of cholinergic synapses suggests that cholinergic transmission in the fascia dentata is a complex event. Next, the Golgi/EM technique was applied to Vibratome sections that contained retrogradely labeled neurons in the hilar region of the fascia dentata following horseradish peroxidase (HRP) injection into the contralateral hippocampus. With this combined approach some of the hilar cells projecting to the contralateral side were identified as mossy cells by the presence of retrogradely transported HRP in thin sections through these Golgi-impregnated and gold-toned neurons. Our findings suggest that the mossy cells are part of the commissural/associational system terminating in the inner molecular layer of the fascia dentata. They are mainly driven by hilar collaterals of granule cell axons that form giant synapses on their dendrites. Finally, the Golgi/EM procedure was used to study the differentiation and developmental plasticity of hippocampal and dentate neurons in transplants and slice cultures of hippocampus. Under both experimental conditions, the differentiating neurons are deprived of their normal laminated afferent innervation but develop their major cell-specific characteristics including a large number of postsynaptic structures (spines). As revealed in thin sections of gold-toned identified cells, all these spines formed synapses with presynaptic boutons suggesting sprouting of the transplanted and cultured neurons, respectively. Altogether, the present report demonstrates the usefulness of the Golgi/EM technique, particularly of the section impregnation procedure, for a variety of studies requiring the identification of individual neurons at the ultrastructural level. PMID- 1295617 TI - Comparison of bone marrow transplantation and chemotherapy for acute leukemia. PMID- 1295618 TI - Specific cytokine regulators and their therapeutic potentials--an overview. PMID- 1295619 TI - Progressive spastic paraparesis associated with human T-cell leukemia virus type I (HTLV-I). AB - Patients with progressive spastic paraparesis (PSP), commonly middle-aged women, are distributed throughout the country of Chile. During the three years from 1987 to 1990, we collected 83 cases of PSP from among 225 patients with various neurological diseases. The clinical picture was of a bilateral pyramidal syndrome, with sensory deficits in only 15.5% of the cases, and a slow illness progression in the majority of them. In patients with PSP, antibody to human T cell leukemia virus type I (HTLV-I) was analyzed by enzyme linked immunosorbent assay (ELISA) and confirmed by western blot analysis. Forty-five (54.2%) patients were anti-HTLV-I antibody positive in cerebrospinal fluid (CSF) and peripheral blood. Among them, 2 patients had leukemia/lymphoma and one had Sjogren syndrome. In the laboratory study of seropositive PSP, mononuclear pleocytosis was found in 35.7%; there was an abnormal increase of the IgG index in 66.6% and an increase in CD2 in blood and CSF, and CD4 in blood. A delayed latency of somatosensory evoked potentials was observed in 90.9%. The neuropsychological study revealed a WAIS with a mean verbal IQ of 80.7 and a mean performance IQ of 84.8. The most impaired items were digit symbol and digit span. Seven subjects (18.9%) with anti HTLV-I antibody were found among 37 relatives from 19 anti-HTLV-I positive cases of PSP. PMID- 1295620 TI - Hypereosinophilic syndrome accompanied with necrosis of finger tips. AB - We report a case of hypereosinophilic syndrome (HES) with marked eosinophilia (59.7%) and mononeuritis multiplex (upper limbs and buttocks). Necrosis of the finger tips was the primary manifestation which simultaneously occurred on both sides. These clinical manifestations were improved dramatically by subsequent steroid therapy. Interestingly, an elevation of serum tumor necrosis factor (TNF) was observed. These findings suggest that TNF may play a role in the etiology of necrosis of the finger tips. PMID- 1295621 TI - Charcot-Marie-Tooth disease with diaphragmatic weakness. AB - A 61-year-old man, who suffered from Charcot-Marie-Tooth disease (CMT) for 44 years, was evaluated for the respiratory disorder. He had diaphragmatic dysfunction induced by phrenic nerve disturbance. In this patient, central type apnea and hypopnea related to diaphragmatic weakness occurred during REM sleep, which induced accessory inspiratory muscle inhibition. Respiratory muscle dysfunction had not been generally recognized in CMT until recently, but its significance should be emphasized. PMID- 1295622 TI - Crohn's disease associated with diffuse lymphoid hyperplasia of the large intestine: a possible role of the lymph follicle in HLA-DR antigen expression on epithelium. AB - A 14-year-old girl diagnosed as Crohn's disease had lymphoid hyperplasia throughout the large bowel. Biopsy specimens from the lymphoid hyperplasia demonstrated non-caseous granulomas within the lymph follicles. An immuno histochemical study of biopsy specimens showed that HLA-DR antigens were expressed on epithelium close to the lymph follicle, which was observed in all specimens containing the lymph follicle. This case provides evidence for the importance of the lymph follicle in the etiopathogenesis of Crohn's disease by demonstration of non-caseous granulomas within the lymph follicle and expression of HLA-DR antigens on epithelium close to the lymph follicle. PMID- 1295623 TI - Acquired chronic pure red cell aplasia successfully treated with intravenous pulse methylprednisolone therapy. AB - A 65-year-old male patient developed acquired chronic pure red cell aplasia (PRCA) associated with hypergammaglobulinemia and positive Coombs' test during the treatment of eosinophilic pneumonia with prednisolone (PSL). His PRCA was treated with oral PSL at a dose of 60 mg/day for 3 weeks, but anemia further progressed. Immediately after high-dose intravenous pulse methylprednisolone therapy (1 g/day for 3 days) however, reticulocyte crisis occurred and his anemia rapidly improved. He has been in complete remission under a maintenance dose of PSL for more than 2 years. This patient indicates that high-dose intravenous methylprednisolone therapy is one of the useful treatments, not only for constitutional PRCA, but also for acquired chronic PRCA. PMID- 1295624 TI - Malignant lymphoma localized in the abdomen: detection of Ig gene rearrangement from the specimen obtained by percutaneous lymph node biopsy. AB - A 32-year-old man was admitted to our hospital because of lumbago and an abdominal mass revealed by abdominal ultrasonography. Abdominal CT scan and MRI revealed multiple para-aortic lymph node swelling involving several arteries and veins. As there was no superficial lymph node swelling, percutaneous lymph node biopsy was performed under ultrasonographic guide. Although non-Hodgkin's lymphoma, diffuse, small cell type was suspected by light microscopic study, the monoclonality of the lymphocytes in the obtained specimen was not clear by the immunohistochemical study. Southern blot hybridization analysis of the biopsy specimen revealed the rearrangement of IgH and IgL (lambda) chain gene, indicating the existence of monoclonal proliferation of lymphoma cells. The DNA analysis appears useful for the differential diagnosis of lympho-proliferative diseases. PMID- 1295625 TI - Medial longitudinal fasciculus syndrome associated with a subdural hygroma and an arachnoid cyst in the middle cranial fossa. AB - A 60-year-old man complaining of diplopia and vertigo showed bilateral medial longitudinal fasciculus (MLF) syndrome. The CT scan revealed a space-occupying lesion with watery fluid in the left cranial fossa, which was divided into two parts by a thin septum. Surgical trepanation was performed followed by 4 weeks of prednisolone therapy. He was completely cured 5 months later. The plausible causes of MLF syndrome relevant to preexisting space-occupying lesions are discussed. PMID- 1295626 TI - Primary angiosarcoma of the right atrium detected by magnetic resonance imaging. AB - A 20-year-old woman with a primary angiosarcoma of the right atrium is reported. The patient had a cardiorespiratory arrest due to cardiac tamponade with bloody pericardial effusion. Magnetic resonance imaging (MRI) revealed a tumor, which was corroborated by selective coronary angiography. Open-heart surgery was performed. The tumor relapsed however, and she died four months after operation. The tumor was undetectable by echocardiography, but MRI demonstrated a heterogeneous mass with focal areas of high- and low-signal intensity in the right atrium, suggesting that MRI may allow characterization of cardiac tumors. PMID- 1295628 TI - Carbamazepine-induced systemic lupus erythematosus-like disease. AB - A 14-year-old female developed systemic lupus erythematosus (SLE)-like symptoms, rash, fever, leukopenia and positive anti-nuclear antibody (ANA) two weeks after administration of carbamazepine (CBZ; Tegretol) used against benign Rolandic epilepsy. Clinical symptoms and leukopenia normalized after discontinuation of CBZ and administration of prednisolone at 40 mg. The cases of CBZ-induced SLE reported in the literature were reviewed. PMID- 1295627 TI - Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease. AB - After 9 years of treatment for Parkinson's disease, a 68-year-old woman developed the complications of neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) while she was still receiving levodopa, bromocriptine and amantadine hydrochloride. The patient displayed a high fever (40 degrees C), impaired consciousness, marked systemic muscle rigidity, tremor and bloody stools. The diagnosis of NMS and DIC was made on the basis of the symptoms and the results of blood serological tests. The antiparkinsonian drugs that had been administered until her admission to our hospital were continued unchanged, while the NMS was treated with dantrolene sodium and the DIC, with nafamostat mesilate. Both of the above-mentioned therapies were effective. The present case is rare in that the patient developed NMS and DIC during treatment and not after the discontinuation of the antiparkinsonian drugs. PMID- 1295629 TI - A patient with severe iron-deficiency anemia and memory disturbance. AB - A 56-year-old woman presented with severe iron-deficiency anemia and memory disturbance. She had been in a state of severe iron deficiency for many years due to an unbalanced diet. Aerobic exercise test revealed an abnormal elevation of lactate and pyruvate reflecting mitochondrial dysfunction. After iron replacement therapy, WAIS verbal IQ score improved from 63 to 83, and levels of lactate and pyruvate on aerobic exercise test were normalized. We raise the possibility that severe and long-term iron deficiency anemia may cause memory disturbance due to mitochondrial dysfunction. PMID- 1295630 TI - Insulin-dependent diabetes mellitus showing microangiopathic hemolytic anemia and chronic disseminated intravascular coagulation. AB - It has been reported that microangiopathic hemolytic anemia occasionally occurs in patients with severe diabetic microangiopathy. We report a case of insulin dependent diabetes mellitus in whom microangiopathic hemolytic anemia and chronic disseminated intravascular coagulation (DIC) were thought to be complicated. The patient showed fragmentation hemolytic anemia and progressive diabetic microangiopathy, together with a mild elevation of serum fibrin(ogen) degradation products. Considering the state of chronic DIC, heparin therapy was started, but mild hemolysis persisted. It is possible that microangiopathic hemolytic anemia and chronic DIC cause a vicious cycle in patients with severe diabetic microangiopathy, leading to rapid progression of diabetic microangiopathy. PMID- 1295631 TI - Severe Guillain-Barre syndrome in aged patients: the effect of plasmapheresis. AB - We report two aged patients with Guillain-Barre syndrome (GBS), in whom the rapid progression necessitated the use of a respirator. The first case, a 72-year-old woman, needed a respirator on the 5th day after onset of illness and the second case, a 74-year-old woman, needed a respirator on the 23rd day. We treated the first patient with plasmapheresis; the second patient underwent plasmapheresis as well as a large dose of intravenous methylprednisolone. Both patients showed remarkable recovery and did not need the respirator from the early stages. It was suggested that plasmapheresis is beneficial for treatment of aged patients with severe GBS, who necessitate the support of a respirator, because it prevents the decline in functional status by shortening the period of hospitalization. PMID- 1295632 TI - Cytophagic histiocytic panniculitis with atypical lymphocytes in peripheral blood. AB - A 26-year-old female patient developed high fever, hepatosplenomegaly and subcutaneous nodules. Atypical lymphocytes were present in the peripheral blood. Skin biopsy revealed lobular panniculitis. Bone marrow examination showed prominent phagocytosis by benign histiocytes. The diagnosis of cytophagic histiocytic panniculitis was made, and the disease has been well controlled with oral prednisolone. This is the first report of cytophagic histiocytic panniculitis with atypical lymphocytes in the peripheral blood, which are frequently seen in virus-associated hemophagocytic syndrome. This observation suggests that underlying viral infection may be one factor in the development of cytophagic histiocytic panniculitis. PMID- 1295633 TI - Ganglioneuroblastoma with disseminated bone marrow infiltration in an adult. AB - Ganglioneuroblastoma is an extremely rare neoplasm of adults. We present a case of adrenal ganglioneuroblastoma in a 47-year-old female with disseminated bone marrow involvement. Bone marrow involvement was the major manifestation which determined the mortality of this patient. This case suggests that the diagnosis of bone marrow involvement should be carefully considered even in adult-onset ganglioneuroblastoma. PMID- 1295634 TI - Cushing's syndrome due to primary adrenocortical nodular dysplasia, cardiac myxomas, and spotty pigmentation, complicated by sarcoidosis. AB - A 23-year-old male patient revealed hypercortisolism with stigmata of Cushing's syndrome, and post-operative pathological examination demonstrated primary adrenal nodular dysplasia. Because of the presence of cardiac myxomas and skin pigmentation, the diagnosis of Carney's complex was given. After the control of hypercortisolism by adrenalectomy, the patient experienced iridocyclitis and bilateral hilar lymphadenopathy with elevated levels of serum angiotensin converting enzyme and lysozyme, all of which indicated the presence of sarcoidosis. Despite the numerous recent descriptions concerning Carney's complex, an association with sarcoidosis has not yet been documented. Moreover, the sequential occurrence of sarcoidosis after adrenalectomy suggests an etiological link between these two rare disorders. PMID- 1295636 TI - Bone marrow purging prior to autologous transplantation. AB - Our data suggest that ex vivo bone marrow purging using monoclonal antibodies (MoAbs) and sheep-anti-mouse immunobeads (SAM beads) prior to autologous bone marrow transplantation (ABMT) allows satisfactory tumor cell reduction without critical stem cell losses. Nevertheless, there is only a reduction but no elimination of tumor cells. The consequences will have to be clinically discussed. PMID- 1295635 TI - Freezing technique and quality of fresh-frozen plasma. AB - Cell-poor plasma was prepared by apheresis from 10 donors. From each donor, an amount of 200 ml was frozen rapidly to -40 degrees C in standard blood bags, and a further 200 ml was frozen slowly to -20 degrees C. Before freezing and after thawing, plasma samples were collected and frozen to -70 degrees C pending analysis. Coagulation factor VIII activity was reduced to 90% by rapid freezing and to 80% by slow freezing. Factor V was not influenced by rapid freezing, but slow freezing reduced the levels to 92% of the pre-freezing levels. In some of the plasma bags a slight increase in fibrinopeptide A occurred. However, soluble fibrin, thrombin-antithrombin complexes and spontaneous proteolytic activity were not altered by freezing. The beta-thromboglobulin increased slightly with slow freezing. Moreover, in a separate experiment, evaluating the possible effects of refreezing plasma samples, an increase in beta-thromboglobulin was also recorded, while the levels of factors VIII and V and von Willebrand factor were not affected. The changes in some variables, which were recorded in the cell-poor plasma, frozen soon after the blood donation at a slow freezing rate, must be regarded as insignificant in most clinical situations. PMID- 1295637 TI - Evaluation of a monocyte enrichment procedure using the blood cell separator Fresenius AS 104. AB - The small number of circulating monocytes in peripheral blood makes it difficult to collect enough cells for studies on the metabolism and analysis of receptor functions of this cell type for diagnostic aims and treatment. Therefore, a new procedure to enrich monocytes from peripheral blood using the cell separator Fresenius AS 104 was developed and evaluated. The separation is done using the tubing set 'P1Y-Gran-collect', which is a closed system with a single-stage separation chamber. The procedure is running continuously, while the cells are harvested cyclically. After processing of 4.9 l whole blood an average yield of (2.47 +/- 2.05) x 10(9) monocytes could be collected with an efficiency of 46 +/- 20%. The monocyte enrichment procedure using the Fresenius AS 104 provides a sufficient number of cells for the next steps: purification and concentration of the cells for drug monitoring, cell culturing, receptor analysis and further in vitro diagnostics. PMID- 1295638 TI - Thrombotic thrombocytopenic purpura: a multimodality model of treatment including plasma exchange, i.v. immunoglobulin, prednisone, antiplatelet agents, vincristine and splenectomy. AB - Thirteen patients with thrombotic thrombocytopenic purpura were treated at our facility between 1985 and 1991. All patients were treated with plasma therapy (both plasma exchange and plasma infusions), prednisone, intravenous immunoglobulin, and antiplatelet agents. Twelve patients achieved remission (92.3%). One patient died from cerebral hemorrhage. Vincristine was administered to 5 patients who did not respond after the first two plasmaphereses. Splenectomy was performed in a patient who relapsed four times within a 2-year period. From the 12 patients achieving remission, 11 have been still in remission for a period of 3 to 69 months. PMID- 1295639 TI - [24th annual meeting of the German Association for Histocompatibility. Essen, 12 14 November 1992. Abstracts]. PMID- 1295640 TI - The nature of nursing. Interview by Julie Goldsmith. PMID- 1295642 TI - Inspiring a new view of public health. Interview by Andria Hine. PMID- 1295641 TI - Knowledge is power. PMID- 1295643 TI - Scientist wins one for women. Interview by Julie Goldsmith. PMID- 1295644 TI - [Anti-HIV activity of complex isoborneol ethers]. PMID- 1295645 TI - [Limitation of the conformational mobility of DNA is maintained in transcriptionally active nucleosomes]. PMID- 1295646 TI - Native healing in Puget Sound. PMID- 1295647 TI - Oscar Howe: images of Native American life and death. PMID- 1295648 TI - The healing arts and the Illinois Indian tribe. PMID- 1295649 TI - Native American women and forced sterilization, 1973-1976. PMID- 1295650 TI - Pregnancy outcome of preterm premature rupture of the membranes before 28 weeks. AB - From January 1987 to December 1990 at Chang Gung Memorial Hospital, the fetal membrane ruptured in 47 singleton pregnancies at the 20th to the 28th gestational weeks. Sixty-six percent of the patients delivered within three days and 91.5% within one week. Only six (12.8%) patients carried their pregnancies over the 28th week. Of the 47 patients, 16 (34.0%) developed clinical evidence of chorioamnionitis during the latent period. The development of chorioamnionitis was not related to any of clinical factors [gestational age at rupture of the membranes, duration of rupture of the membranes before admission, positive endocervical culture, tocolysis, latent period or the presence of oligohydramnios (p > 0.05)]. The neonatal survival rate was 12.7% (six out of 47). Neonatal death was mainly attributable to prematurity. Gestational age beyond the 28th week and body weight greater than 1000 gm are two factors contributing to fetal survival. When fetal lung maturity has not occurred expectant management in the absence of infection is an alternative treatment. PMID- 1295651 TI - Clinical analysis of surgical treatment for tuboovarian abscess. AB - The role of copious irrigation and drainage in the treatment of tuboovarian abscess (TOA) is crucial, especially for the patients who want to remain fertile. Some have used vaginal drainage via posterior colpotomy for patients with TOA, whereas others preferred irrigation using large-bore drains. In this study, we reported 31 cases of TOA. We found that for women who want to conceive again the best method of treatment is conservative surgery plus low pressure sump tube drainage. PMID- 1295652 TI - A clinical evaluation of comprehensive dental treatment for children under general anesthesia. AB - The purpose of this study is to evaluate the comprehensive dental treatment for children under general anesthesia. From 1989 to 1991, 57 children with mean age of 3 years 2 months were treated, followed up with a minimal of 1 year. This procedure allows the dentition to be restored in one visit. Further care including preventive options and behavior shaping was provided on a 3-6 months recall schedule. The reasons for general anesthesia are that these children were either unable to accept treatment because of handicaps, extreme fear or young age. Their mean number of decayed tooth was 15 (Standard Deviation, SD = 5) and nearly three quarters of the children were under 6 years old. The most frequent treatment procedures were the extraction of teeth, composite resin restoration and Ni-Cr crown restoration. The Ni-Cr crown (1.7% failure rate) was more successful than the amalgam and composite resin restoration (9.7% failure rate). Pedo-strip crown had the highest failure rate (22%) for anterior teeth restoration. Nineteen children needed retreatment with conventional behavior guide. Six children had new caries and required further treatment. Thirty eight children returned for regular recall during the minimal 1 year follow-up period. PMID- 1295653 TI - [Epidemiology of scrub typhus in Matsu Peikang Island]. AB - A retrospective survey of the epidemiology of scrub typhus in 1990 in Matsu Peikang Island was made at the end of December of 1990. The diagnosis of scrub typhus was based on the presence of escar, typical clinical manifestation and good response to tetracycline treatment. There were 89 cases of scrub typhus studied, and except for one civilian, the other 88 cases were military personnel, occurring in 2.2% of the total military personnel on the island. However it occurred in 0.08% of the civilian population. Seasonal distribution of scrub typhus was limited to between June and October of 1990. The peak incidence occurred in July. Scrub typhus was distributed over the whole island. A higher incidence of scrub typhus occurred in soldiers and sergeants than in officers. A significant different incidence was found in different units. No fatalities were reported. Different units. No fatalities were reported. Different military activities, duties and the location of the military unit may affect the incidence of scrub typhus. The scrub typhus epidemic was also related to temperature. PMID- 1295654 TI - [Clinical evaluation of gingival tissue restored with stainless steel crown]. AB - The use of stainless steel crown for the restoration of primary molars is widely accepted in pediatric dentistry. There has been a concern regarding their effect on the health of the gingival tissue. It is a possibility that the preformed crown may be a contributing cause of gingivitis. This study evaluated one hundred and thirty-seven crowns in forty-five patients who had received pedodontic treatment at Chang Gung Memorial Hospital. The results indicated that the majority of stainless steel crowns had one or more defects, with crown crimping being the most common error. According to what the paired t-test showed, non ideal crowns indicated that the gingival index was significantly higher than the entire mouth and control teeth. However the supragingival plaque accumulation of these teeth was significant lower than the entire mouth and control teeth. There was only a moderate positive correlation between supragingival plaque and gingivitis. The operator is necessary to adapt the stainless steel crown margin as closely as possible to the tooth and to avoid the mechanical defect of a crown. It minimizes the irritation of gingival tissue and diminishes the bacterial adherence of subgingival plaque, therefore preserving the health of gingival tissue. PMID- 1295656 TI - Trisomy 18 (Edwards syndrome): report of two cases. AB - Edwards syndrome is the second most common autosomal trisomy syndrome, resulting from an extra chromosome in chromosome 18. Recently we encountered two cases with the following representative features: intrauterine growth retardation, polyhydramnios, low-set ears, micrognathia and clenched hands. Both cases were female newborns and had an abnormal karyotype 47, XX, 18. PMID- 1295655 TI - [Implementation of stereotactic focal radiotherapy using 10 MV x-ray]. AB - Stereotactic focal irradiation is also called stereotactic radiosurgery by some neurosurgeons. This irradiation is used for the treatment of brain AVM (arterio venous malformation) and small tumor. Application of stereotactic focal irradiation was developed with CRW (Cosman-Roberts-Wells) stereotactic device and two dimensional (2D) computer treatment planning system using 10 MV x-ray from a linear accelerator. This process of irradiation includes: (a) Identification and localization of a target volume in CRW stereotactic frame by CT scan or angiography. (b) To verify the alignment, a linear accelerator was used as a simulator to take portal films in anterior and lateral views. This was done to ascertain the angles between arc therapy, to encompass the target volume, and to exclude the critical organs such as lens at 0 degrees, 45 degrees, 90 degrees and 315 degrees couch angles. (c) A 2D computer treatment planning system was used to generate an isodose curve distribution for each couch angle. Then this was used to calculate the monitor unit per degree for rotation treatment. (d) 10 MV x-ray was used to implement the stereotactic focal radiotherapy. PMID- 1295657 TI - Subcapsular hematoma of spleen--a complication following extracorporeal shock wave lithotripsy for ureteral calculus. AB - Splenic trauma with hematoma following extracorporeal shock wave lithotripsy (ESWL) is very rare. We reported a case of subcapsular hematoma of spleen with impending rupture following ESWL for ureteral calculus. This case was noted to have liver cirrhosis and splenomegaly, and received a total of 2000 shock waves under 18 kilovoltage. The subcapsular hematoma occurred 2 months later. Splenectomy was undertaken for a symptomatic huge subcapsular hematoma and thrombocytopenia. We reviewed the literature and concluded that portal hypertension with severe coagulopathy are contraindications for ESWL, even in case with ureteral calculus. PMID- 1295658 TI - [Low dose radioiodine treatment of papillary thyroid carcinoma in a child--a case report]. AB - The thyroid carcinoma is rare in children and the optimal management is rather controversial. We report a case of a 7-year-old boy who had right neck masses and proved to be papillary thyroid carcinoma after near-total thyroidectomy. Post operative 20 mCi radioiodine-131 (I-131) ablation scan, lung metastasis was suspected but the chest X ray was normal. After being lost to follow up for 4 years, the patient returned with the complaints of cough; the chest X ray was still normal. He then received 5 treatment with low dose (30 mCi) I-131 therapy and continued thyroxine replacement. Progressive decrease both of the thyroglobulin level and the intensity of radioactivity of lung were noted. After a total doses of 193 mCi I-131 therapy, neither pulmonary fibrosis nor bone marrow suppression was seen. Although the low dose (< or = 30 mCi) I-131 therapy was recommended, it was limited for the ablation therapy of the remnant thyroid tissue. Upon consideration of economics and the convenience of not being admitted to the isolation room, the low dose I-131 therapy seems feasible for children with thyroid carcinoma with systemic disease. However, the long term efficacy needs further evaluation. PMID- 1295659 TI - [Cushing's syndrome with pregnancy. Report of three cases]. AB - Cushing's syndrome with pregnancy is rare, and only about 60 cases have been reported. In the recent 4 years, 3 cases were diagnosed in Chang Gang Memorial Hospital. They presented with serious maternal complications early in the second month of pregnancy, including hypertension, proteinuria and lower leg edema. Unfortunately it was not diagnosed until the 20th week of pregnancy. They had the same hormone profile as other Cushing's syndrome patients who were not pregnant. Under the supportive treatment they had outcomes of two premature deliveries and one still birth. Just after delivery all patients received left adrenalectomy and pathology showed adenoma. All of them had good recovery courses. According to the literature, early treatment (surgical operation, medical treatment, or irradiation) could decrease maternal morbidity and fetal loss rate. PMID- 1295660 TI - Ions, water, and energy in brain cells: a synopsis of interrelations. AB - A brief summary is given of some of the key points of the individual contributions at this International Brain Research Organization satellite meeting, presenting up-to-date, expert knowledge of energy metabolism, ionic turnover, and cell swelling at the cellular level of the mammalian central nervous system. On the basis of this material, we are also suggesting a unified concept of reciprocal interactions between metabolism, ion carriers, and ion channels, which are of crucial importance for the function of the central nervous system. PMID- 1295661 TI - Changes in the glucose transporter of brain capillaries. AB - Brain capillary endothelium has a high density of the GLUT-1 facilitative glucose transporter protein. This is reasonable in view of the brain's high metabolic rate for glucose and its isolation behind unique capillaries with blood-brain barrier properties. Thus, the brain endothelium, which constitutes less than 0.1% of the brain weight, has to transport glucose for the much larger mass of surrounding neurons and glia. I describe here the changes that occur in the density of glucose transporters in brain capillaries of subjects with Alzheimer disease, where there is a decreased cerebral metabolic rate for glucose, and in a novel clinical entity characterized by defective glucose transport at the blood brain barrier. In subjects with Alzheimer disease, cerebral microvessels showed a marked decrease in the density of the glucose transporter when compared with age matched controls, but there was no change in the density of glucose transporters in erythrocyte membranes. Thus, I believe that the decreased density of glucose transporters in the brains of subjects with Alzheimer disease is the result rather than the cause of the disease. In contradistinction, the primary defect in glucose transport at the blood-brain barrier in subjects with the recently described entity is associated with decreased density of GLUT-1 in erythrocyte membranes. PMID- 1295663 TI - Oxidative metabolism in neuronal and non-neuronal mitochondria. AB - Methodological advances have allowed the isolation of two populations of synaptic (SM and SM2) and two populations of nonsynaptic (A and B) mitochondria from rat forebrain. All four populations of brain mitochondria are metabolically active and essentially free from nonmitochondrial contaminants. They (SM, SM2, A, and B) can oxidize a variety of substrates; the best substrate is pyruvate. With pyruvate as the substrate, the respiratory control ratios (i.e., state 3/state 4) in all four populations are routinely > 6. Results from numerous enzyme activity measurements provide strong support for the hypothesis that brain mitochondria are very heterogeneous with respect to their enzyme contents and that the enzymatic activities in a particular population of mitochondria, be they synaptic or nonsynaptic, differ from those in another population of mitochondria derived from either the same or another brain region. The major methodological advances in brain mitochondrial isolation greatly facilitate metabolic studies. For example, we have demonstrated that the K+ stimulation of brain mitochondrial pyruvate oxidation is mediated through a K(+)-induced elevation of the activation state of the pyruvate dehydrogenase complex and the K+ stimulation of the flux through the pyruvate dehydrogenase complex. Our previous and ongoing studies using primary cultures of hypothalamic neurons and astrocytes are consistent with the proposal that brain cells are heterogeneous with respect to their capabilities in energy metabolism. I can envisage that in the no-so-distant future, one could adapt these preparations of cells as the starting material for the isolation of mitochondria of known cellular origin for metabolic studies. PMID- 1295662 TI - Energy metabolism in developing brain cells. AB - During development different energy substrates are available to cells in brain in plentiful supply. The metabolic environment, which is dictated by the milk diet rich in fat, ensures that substrates in addition to glucose are available as fuels. Some substrates serve readily as primary fuels for respiration, whereas other substrates can serve other functions in addition to serving as primary fuels. Primary fuels for respiration serve to supply acetyl CoA directly and as a result always have first priority. With this criteria in mind, a consideration of substrate priority for respiration by developing brain is presented. Many studies in the decade, 1970-1980, in human infants and in the rat pup model show that both glucose and the ketone bodies, acetoacetate and D-(-)-3-hydroxybutyrate, are taken up by brain and used for energy production and as carbon sources for lipogenesis. Products of fat metabolism, free fatty acids, ketone bodies, and glycerol dominate metabolic pools in early development as a consequence of the milk diet. This recognition of a distinctive metabolic environment from the well fed adult was taken into consideration within the last decade when methods became available to obtain and study each of the major cell populations, neurons, astrocytes, and oligodendrocytes in near homogeneous state in primary cultures. Studies on these cells made it possible to examine the distinctive metabolic properties and capabilities of each cell population to oxidize the metabolites that are available in development. Studies by many investigators on these cell populations show that all three can use glucose and the ketone bodies in respiration and for lipogenesis. Only one cell type, the astrocytes, can beta oxidize fatty acids such as octanoate. By comparing the production of labeled carbon dioxide from glucose labeled on carbon-1 compared with carbon-6, it is clear that all three cell populations are capable of active hexose monophosphate shunt activity. Neurons and oligodendrocytes are capable of making good use of acetoacetate and D-(-)-3-hydroxybutyrate, whereas the best substrate for astrocytes is fatty acid. Under comparable conditions of incubation with astrocytes, fatty acids serve better than ketones, which in turn serve better than glucose in respiration. Some of the major factors that can explain the differing observations by different investigators on the capacity for substrate oxidation are presented. Over the last decade, astrocytes have captured the attention of neurobiologists because they have special attributes as metabolic support cells for the management of intermediary metabolism in brain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1295664 TI - Physiologic coupling of glial glycogen metabolism to neuronal activity in brain. AB - Brain glycogen is localized almost exclusively to glia, where it undergoes continuous utilization and resynthesis. We have shown that glycogen utilization increases during tactile stimulation of the rat face and vibrissae. Conversely, decreased neuronal activity during hibernation and anesthesia is accompanied by a marked increase in brain glycogen content. These observations support a link between neuronal activity and glial glycogen metabolism. The energetics of glycogen metabolism suggest that glial glycogen is mobilized to meet increased metabolic demands of glia rather than to serve as a substrate for neuronal activity. An advantage to the use of glycogen may be the potentially faster generation of ATP from glycogen than from glucose. Alternatively, glycogen could be utilized if glucose supply is transiently insufficient during the onset of increased metabolic activity. Brain glycogen may have a dynamic role as a buffer between the abrupt increases in focal metabolic demands that occur during normal brain activity and the compensatory changes in focal cerebral blood flow or oxidative metabolism. PMID- 1295665 TI - Energy metabolism at the cellular level of the CNS. AB - Evidence is accumulating that interactions between different cell types are of paramount importance for CNS function, for example, release of the excitatory transmitter glutamate from neurons and its preferential uptake into astrocytes. Some information is also available about energy metabolism in different cell types, or more often in models of different cell types (e.g., synaptosomes, cultured neurons, cultured astrocytes). In this review an attempt is made not only to correlate information obtained with different cell models but also to integrate this information with in vivo data, with histochemical observations, and with results obtained using brain slices. The emerging patterns indicate that neurons, synaptosomes, and astrocytes are all capable of complete glycolysis and oxidation of glucose. Elevated extracellular concentrations of potassium, known to occur in vivo, enhance energy metabolism by mechanisms that differ between neurons and astrocytes and to a large extent serve to reaccumulate extracellular potassium ions into adjacent cells. Monoaminergic agonists also stimulate energy metabolism, but mainly or exclusively in astrocytes. Profound differences are found between the effects of excess potassium and of aminergic transmitters, suggesting that high potassium concentrations enhance neuronal-astrocytic interactions, whereas the monoamines may tend to dissociate metabolic events in neurons and in astrocytes. PMID- 1295666 TI - Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies on retina. AB - CNS tissue is well known to have large energy requirements. However, because of the difficulty of measuring rates of energy usage, relatively little is known about which cell types and which neurophysiological functions are the principal energy users. In experiments performed on rabbit retina in vitro, it was possible to measure O2 consumption and lactate production with the retinas under resting conditions and in different states of physiological activity. Resting energy consumption was large, as has been previously reported, and there were increases of up to 2.3 times with activity. Under some circumstances, the demands appeared to exceed the energy available. It was calculated that less than 5% of the energy generated by the retina was used for "vegetative metabolism" (i.e., for the anabolic reactions essential for viability), so that even in the resting state, the great majority of the energy usage appeared to be for function-related processes. This conclusion received further support from the finding that 50% of the energy generated was used for Na+ transport. The data obtained on retina are compared with published data on brain, which also suggest that a large fraction of the energy generated is used for function-related processes. It seems reasonable to conclude that by reversibly blocking the energy-demanding processes responsible for neurophysiological functioning, it would be possible to eliminate most of the energy requirements of CNS tissue and to reduce markedly its vulnerability to hypoperfusion. PMID- 1295667 TI - Glycolytic and oxidative metabolic contributions to potassium ion transport in rat cerebral cortex. AB - Putative roles of glycolytic and oxidative metabolism in the removal of potassium ion from the extracellular space were examined in rat cerebral cortex. In response to direct electrical stimulation of the cerebral surface, the activity of extracellular potassium ion (Ko+) transiently increased. Inhibition of glycolysis with iodoacetate prolonged the time required for dissipation of the elevated Ko+. This slowing was most evident in the early period after stimulation, when Ko+ was relatively high. Levels of high-energy intermediates were unchanged by iodoacetate. In contrast, severe hypoxemia was without effect during the early phase of K+ removal but hypoxemia slowed the later restoration of the Ko+ baseline. These data demonstrate that the rapid removal of potassium ion from the extracellular space following intense neuronal activity is aided by the Embden-Myerhoff metabolic pathways and perhaps by direct coupling of ATP produced by glycolysis. We suggest that removal of potassium ion from the brain extracellular space depends on two ATP pools, one derived from oxidative phosphorylation, the other from glycolysis. The glycolytic ATP pool may be most involved in the early and rapid phase of potassium clearance; the oxidative ATP pool may be more associated with the second and slower phase of Ko+ clearance, and with the maintenance of the Ko+ baseline under 'resting' conditions. PMID- 1295668 TI - Coupling of metabolism and electrical activity in cortical astrocytes. AB - Cortical mouse astrocytes in culture were impaled with two-channel microelectrodes. These mouse astrocytes have the same responses to different K+ concentrations, ouabain, and glutamate as cultured rat astrocytes, with the exception that a large barium-sensitive K+ conductance clamps the membrane potential at the K+ equilibrium potential. Glycolytic and mitochondrial inhibitors have little effect on the mouse astrocytes. Total blockade of energy metabolism leads to an irreversible, calcium-dependent depolarization, but only if applied for longer than 45 min. Increasing the extracellular K+ concentration to 60 mM increases the intracellular K+ concentration by 43 mM and the bicarbonate concentration by 22 mM and leads to a concomitant fast swelling. Together with the 20 mM increase in Cl- concentration reported in the literature this is a good indication for a Boyle- and Conway-mediated K(+)-anion influx with water. This influx is accomplished by the depolarization-induced opening of Cl- channels as reported in the literature. In conclusion, ischemia-like conditions have little direct, immediate impact on astrocytes. In contrast, ischemia-induced release of substances from neurones, such as K+, produces an immediate and fast response. PMID- 1295669 TI - Anoxia-induced extracellular ionic changes in CNS white matter: the role of glial cells. AB - The rapid changes in brain extracellular ion concentrations that occur with anoxia are important in understanding the pathophysiology of anoxic-ischemic brain injury. While previous studies have focused on the ionic changes that occur in gray matter areas of the brain, white matter (WM) is also damaged by anoxia. We describe the changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) that accompany anoxia in WM, and present new results indicating that glial cells directly contribute to the observed fluctuations of these ions. Anoxia-induced changes in [K+]o and pHo were measured with ion selective microelectrodes in the isolated rat optic nerve, a typical WM tract. To assess the contribution of glial cells, recordings were also made in optic nerves that contained only glial cells (produced by neonatal enucleation). Anoxia in WM produced less extreme changes in [K+]o and pHo than are known to occur in gray matter; in WM during anoxia, the average maximum [K+]o was 14 +/- 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 +/- 0.07 pH unit. These extracellular ionic changes were accompanied by rapid shrinkage of extracellular space volume. The ability of optic nerve axons to conduct action potentials was lost in temporal association with the increase in [K+]o. Increasing bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 +/- 0.08 pH unit) and a smaller average increase in [K+]o (9.2 +/- 2.6 mM). The increased glucose concentration presumably enhanced anaerobic metabolism, leading to extracellular lactate accumulation and a greater acid shift.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295670 TI - Relationship between ions and energy metabolism: cerebral calcium movements during ischaemia and subsequent recovery. AB - Intra- and extra-cellular concentrations of calcium were measured in hippocampal neurons of areas CA1 and CA3 during 8 min ischaemia and short-term (up to 60 min) recovery. During an ischaemic insult, [Ca2+]i increased progressively and [Ca2+]e decreased. There were large interneuronal differences, although, in general, rises in [Ca2+]i were much larger in area CA1 than in CA3. Restitution of blood flow was followed by movements of calcium in the directions opposite to those seen during ischaemia: [Ca2+] in the extracellular space gradually rose whereas that inside neurones fell. Within 30-60 min, calcium balance was restored to the original pre-ischaemic level. It is postulated that (i) large increases in [Ca2+]i in cerebral neurones during ischaemia are related to the high density of pathways on neurones that allow calcium entry; (ii) differences in the amount of calcium accumulated during periods of oxygen deprivation between neurones of the Ca1 and CA3 regions are linked to the level of glutamatergic input (and hence excitatory synapses) that the two areas receive; (iii) restitution of blood flow and consequent rapid restoration of ATP synthesis permit reactivation of calcium eliminating mechanisms. These latter involve especially sequestration by the mitochondria and extrusion by the plasma membrane Ca pump, which restore the low cytoplasmic [Ca2+]. PMID- 1295672 TI - Potassium and sodium transport and pH regulation. AB - The excitatory and metabolic events in nervous tissue lead to localized increases in extracellular potassium (K+) and intracellular hydrogen (H+) and calcium (Ca2+) ion concentrations. Even more pronounced increases are seen under pathological conditions and may interfere with the maintenance of cellular function and structure. Most presentations on the second day focused on these processes and the mechanisms for the clearance of K+, H+, and Ca2+ from intra- or extra-cellular compartments. The essential role of glial cells was a returning theme. Extracellular K+ is transported into cells by the Na-K pump and by two other processes, Na-K-Cl2 cotransport and spatial buffering, which both depend on the operation of the Na-K pump. The clearance of H+ from the cytoplasm and into the extracellular space is mediated by Na+ gradient dependent processes, Na+/H+ antiport, Cl-/HCO3- exchange, and Na(+)-HCO3- cotransport. Also the clearance of cytoplasmic Ca2+ is to a large extent mediated by a Na+ gradient dependent process, the Na+/Ca2+ antiport. There is a wide divergence between the rates of Na-K pump mediated K+ influx measured in various cultures of glial and neuronal cells. There is a considerable need for systematic comparison between the functional capacity and the concentration of Na-K pumps in cell cultures and intact nervous tissue. It has not yet been ascertained whether K+ transport as measured in cultured astrocytes is representative for K+ transport in the in situ functioning astrocyte. In astrocytes, glutamate was shown to elicit a rapid intercellular propagation of a rise in cytoplasmic Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295671 TI - Pharmacological properties of excitatory amino acid induced changes in extracellular calcium concentration in rat hippocampal slices. AB - We have studied extracellular ionic changes induced by iontophoretic application of excitatory amino acids in rat hippocampal slices. In contrast to kinetics of changes in [Ca2+]o, kinetics of changes in [K+]o, [Na+]o, [Cl-]o as well as in extracellular space size were comparable for different glutamate receptor agonists. Thus, alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA), quisqualate (quis), and kainate caused reductions in [Ca2+]o followed by an increase of [Ca2+]o above baseline, whereas glutamate, aspartate, N-methyl-D aspartate (NMDA), and DL-homocysteic acid caused only reductions in [Ca2+]o. After blocking the NMDA receptors with ketamine and 2-amino-5- phosphonovaleric acid (2-APV), glutamate-induced decreases in [Ca2+]o were followed by an overshoot. Reduction of the transmembrane Na+ gradient by lowering [Na+]o, blocking of the Na(+)-K+ ATPase by lowering [K+]o, and application of ouabain blocked the overshoots after quis application, whereas vanadate, a blocker of the Ca(2+)-Mg2+ ATPase, had no effects. Lithium enhanced the reductions in [Ca2+]o and blocked the overshoots. Amiloride also reduced the overshoots. All organic Ca2+ entry blockers diminished reductions of [Ca2+]o but increased the overshoots. Inorganic Ca2+ antagonists had variable effects. Ni2+ had similar effects as the organic Ca2+ entry blockers while Cd2+ reduced both the [Ca2+]o decreases as well as the subsequent overshoots. Co2+ had initially a similar action as Ni2+. With prolonged application, [Ca2+]o decreases became augmented and, during wash, overshoots could no longer be elicited. We suggest that the overshoots in [Ca2+]o are due to a combined effect of extracellular space shrinkage and activation of the Na+/Ca2+ exchangers. This would imply that NMDA receptor activation blocks extrusion of Ca2+ from the cells. We tested the hypothesis that quis-induced intracellular Ca2+ release and extrusion of Ca2+ from the cells contributed to the overshoots. Dantrolene was without effect on the quis-induced signals, while ryanodine reduced the overshoots. Caffeine on the other hand diminished the [Ca2+]o decreases with no effects on the overshoots. To test for possible second messenger routes by which NMDA receptor activation might slow Ca2+ extrusion from cells, we investigated the effects of arachidonic acid and N-monomethyl-D- arginine on the quis-induced signals. While these agents reduced decreases in [Ca2+]o, they had no clear effects on the overshoots. Thus a possible route by which NMDA receptor activation may affect Ca2+ extrusion from cells has still to be elucidated. PMID- 1295673 TI - K+ ion regulation in retina. AB - During onset and offset of illumination, considerable changes in extracellular K+ concentration ([K+]c) occur within particular retinal layers. There are two ways in which glial cells may control [K+]c: (1) by space-independent processes, for example, by K+ uptake due to the Na(+)-K+ ATPase, and (2) by space-dependent processes, that is, by spatial buffering currents flowing through K+ channels. Rabbit retinal Muller (glial) cells were studied for expression of mechanisms supporting both kinds of processes. This review demonstrates that rabbit Muller cells have Na-K pumps whose distribution and properties are highly adapted to meet the needs of efficient K+ clearance. Furthermore, spatial buffering currents through specialized K+ channels of Muller cells greatly accelerate retinal K+ clearance during and after stimulation. PMID- 1295674 TI - Mechanism of spreading depression: a review of recent findings and a hypothesis. AB - Spreading depression of Leao (SD) can be provoked by numerous nonspecific mechanical, electrical, and chemical stimuli. A similar, if not identical, phenomenon can be provoked by hypoxia. SD is characterized by drastic depolarization of neurons, severe reduction of membrane resistance, and redistribution of ions across cell membranes. Glial cells also depolarize but retain membrane resistance. Tetraethylammonium hastens the onset of hypoxic SD but reduces the sustained potential shift and K+ outflow from cells; 4 aminopyridine also accelerates SD but has no effect on the voltage shift. N Methyl-D-aspartate receptor antagonists delay the onset of SD, while nickel and cobalt reduce the amplitude of SD-related redistribution of Ca2+. Yet, no specific blocker of SD has been found. Microdialysis of high-K+ solution in hippocampal CA1 region induces recurrent waves of SD propagating semi independently in adjacent tissue layers, and a prolonged unstable depressed state that has not previously been described. Neither the release of K+ ions nor of glutamate is the unique agent of SD propagation. On the basis of recent findings we propose a hypothetical sequence of events that reconcile many of the previously seemingly paradoxical observations. PMID- 1295675 TI - Role of Na/K/Cl cotransport in astrocytes. AB - The kinetic characterization of the Na/K/Cl cotransport of cultured astrocytes and evidence for its involvement in volume regulation and K+ net uptake during K+ clearance are reviewed. Emphasis is put on experimental evidence for a proposed sodium cycle in astrocytes; this cycle involves a Na(+)-K+ ATPase that is stimulated by both a high external K+ and intracellular Na+. Elevated external K+ also stimulates the Na/K/Cl carrier, transporting these ions inward. As a result Na+ is cycled across the membrane, carried inward by the Na/K/Cl carrier, and returned by the Na(+)-K+ ATPase. Both functionally coupled mechanisms lead to intracellular KCl accumulation and inward movements of water to compensate for increased osmolarity. The combined cycle is expected to play a major role in the regulation of physiological K+ levels in the brain. PMID- 1295676 TI - Effect of elevated potassium on the ion content of mouse astrocytes and neurons. AB - Potassium is tightly regulated within the extracellular compartment of the brain. Nonetheless, it can increase 3- to 4-fold during periods of intense seizure activity and 10- to 20-fold under certain pathological conditions such as spreading depression. Within the central nervous system, neurons and astrocytes are both affected by shifts in the extracellular concentration of potassium. Elevated potassium can lead to a redistribution of other ions (e.g., calcium, sodium, chloride, hydrogen, etc.) within the cellular compartment of the brain. Small shifts in the extracellular potassium concentration can markedly affect acid-based homeostasis, energy metabolism, and volume regulation of these two brain cells. Since normal neuronal function is tightly coupled to the ability of the surrounding glial cells to regulate ionic shifts within the brain and since both cell types can be affected by shifts in the extracellular potassium, it is important to characterize their individual response to an elevation of this ion. This review describes the results of side-by-side studies conducted on cortical neurons and astrocytes, which assessed the effect of elevated potassium on their resting membrane potential, intracellular volume, and their intracellular concentration of potassium, sodium, and chloride. The results obtained from these studies suggest that there exists a marked cellular heterogeneity between neurons and astrocytes in their response to an elevation in the extracellular potassium concentration. PMID- 1295677 TI - Intracellular pH in rat brain in vivo and in brain slices. AB - Intracellular pH can be measured quantitatively in rat brain in vivo and in vitro using spectrophotometric detection of the vital dye neutral red. This method preserves spatial information and is compatible with microhistochemistry. The intracellular pH indicated by this method is in close agreement with that indicated by 31P-NMR spectroscopy. During ischemia, intracellular acidification is correlated with tissue lactate accumulation. The spatial distribution of pH values becomes more heterogeneous as the tissue becomes more acidic. Resuscitation from total cerebral ischemia produced by cardiac arrest results in rapid intracellular realkalinization. This realkalinization is at least partially inhibited by amiloride pretreatment. Some neuronal populations, especially in the hippocampal CA1 and CA4 regions, may become more acidic during ischemia and realkalinize more slowly after reperfusion than other tissue regions. The intracellular pH of hippocampal brain slice preparations is more alkaline than expected from in vivo studies. The intracellular pH of the brain slice can be acidified to near neutrality by specific inhibitors of the sodium/hydrogen ion exchanger. PMID- 1295678 TI - The regulation of intracellular pH in cultured astrocytes and neuroblastoma cells, and its dependence on extracellular pH in a HCO3-free solution. AB - Microspectrofluorometry was used to study the regulation of intracellular pH (pHi) in 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-loaded astrocytes and the neuroblastoma-glioma cells of the NG 108-15 line. The cells rapidly regulated pHi during an acid transient induced by an NH4+ prepulse. This regulation was blocked by removal of Na+, or by addition of 1 mM amiloride. The back regulation was also inhibited when extracellular pH (pHc) was lowered. Furthermore, when cells were exposed to buffer with reduced or increased pHc, pHi changed in parallel. Thus, although these cells possess at least one efficient H+ extrusion mechanism, which is likely to be the ubiquitous Na+/H+ antiporter, they fail to regulate pHi to a normal value unless pHc is held constant. The implications of these findings are discussed. PMID- 1295679 TI - Introduction to slow synaptic potentials and their neuromodulation by dopamine. AB - The existence of two muscarinically mediated slow postsynaptic potentials (PSPs) and a noncholinergic (peptidergic) late-slow PSP was established in the 1960s. These have synaptic delays and PSP durations 100-10,000 times those for the nicotinic (fast) excitatory post-synaptic potential (EPSP). Evidence is reviewed for an against the proposal that, in rabbit superior cervical ganglia, the slow (s-) inhibitory postsynaptic potential requires a second transmitter, dopamine, released by muscarinic action on interneurones (the small, intensely fluorescent cells). The s-EPSP in frog ganglia appears only in already depolarized cells by a muscarinic closure of the M (voltage-sensitive K+) channels. But the large s-EPSP in mammalian neurones, not depolarized, is generated largely via other mechanisms, especially one involving cyclic GMP. Dopamine also produces a long term enhancement (LTE) of the muscarinic slow PSPs in rabbit superior cervical ganglia, whether dopamine is applied exogenously or released intraganglionically by preganglionic nerve impulses at 10 s-1. LTE is producible heterosynaptically, and it persists well over 3 h; a noncholinergic (peptide?) transmitter may contribute to the initial 30 min of LTE. LTE is mediated by a D1 receptor coupled to cyclic AMP; it is blocked by cyclic GMP or low Ca2+ or calmidazolium (a calmodulin inhibitor). The modulatory process of LTE has certain similarities to, but also fundamental differences from, the long-term potentiation known in the hippocampus. PMID- 1295680 TI - Extracellular K+, pH, and volume changes in spinal cord of adult rats and during postnatal development. AB - Activity-related transient changes in extracellular K+ concentration ([K+]c), extracellular pH (pHc), and extracellular volume (EC volume) were studied by means of ion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3-14 days of age. Repetitive electrical nerve stimulation (10-100 Hz) in adults elicited increases in [K+]c by about 2.0-3.5 mM, followed by a poststimulation K+ undershoot and triphasic alkaline-acid-alkaline changes in pHc. In 3- to 6-day-old pups, the [K+]c increased by as much as 6.5 mM at a stimulation frequency of 10 Hz, and this was accompanied by an alkaline shift. Increases in [K+]c as large as 1.3-2.5 mM accompanied by an alkaline shift were evoked by a single electrical stimulus. Stimulation in 10- to 13-day-old pups produced smaller [K+]c change and an acid shift, which was preceded by a small initial alkaline shift, as in adult rats. We conclude that glial cells buffer the activity-related [K+]c increase and alkaline pHc shifts. Mg2+ blocked the alkaline but not the acid shift. Acetazolamide had no effect on the alkaline shift but blocked the acid shift. The alkaline shift was enhanced and the acid shift blocked by Ba2+, amiloride, 4-acetamido-4' isothiocyanotostilbene-2,2'-disulfonic acid (SITS), and 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Activity-related acid shifts therefore have a complex mechanism, which includes Na+H+ exchange, Cl /HCO3- exchange, or Na+/Cl-/H+/HCO3- antiport, Na(+)-HCO3- cotransport, and H+ efflux through voltage-sensitive H+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295681 TI - Cell swelling and volume regulation. AB - The extracellular space in the brain is typically 20% of the tissue volume and is reduced to at least half its size under conditions of neural insult. Whether there is a minimum size to the extracellular space was discussed. A general model for cell volume regulation was presented, followed by a discussion on how many of the generally involved mechanisms are identified in neural cells and (or) in astrocytes. There seems to be clear evidence suggesting that parallel K+ and Cl- channels mediate regulatory volume decrease in primary cultures of astrocytes, and a stretch-activated cation channel has been reported. The role of the different channels was discussed. A taurine leak pathway is clearly activated after cell swelling both in astrocytes and in neurones. The relations between the effect of glutamate and cell swelling were discussed. Discussion on the clearance of potassium from the extracellular space was continued. Neither the spatial buffering mechanism nor the role of the Na+/K+ pump was discussed here, but additional possibilities for K+ removal were discussed. At a high extracellular K+ concentration there is a possibility of channel-mediated KCl uptake by the glia cells, and a Na-K-2Cl cotransport system is present in astrocytes and seems to play a role at relatively low extracellular K+ concentrations (6-20 mM). The cotransport system is likely to be regulated, but little is known about its regulation in glia cells. PMID- 1295682 TI - Quantitative analysis of extracellular space using the method of TMA+ iontophoresis and the issue of TMA+ uptake. AB - The tetramethylammonium (TMA+) method for measuring the volume fraction and tortuosity of brain extracellular space is presented in detail. The temporal and spatial distribution of TMA+ in the extracellular space following iontophoresis or pressure microinjection is described by suitable equations and illustrated with graphs. By fitting the equations to the concentration versus time data obtained from measurements with ion-selective micropipettes, the volume fraction and tortuosity can be measured. In addition, the concentration-dependent uptake of TMA+ can be estimated from the given equations. The final section of the paper derives simple numerical estimates of TMA+ loss from the extracellular space by this mechanism. PMID- 1295683 TI - Methods for determination of cell volume in tissue culture. AB - In this paper we present an overview of methods for determining cell volume in both suspension and monolayer cultures. Data from the use of selected methods such as the Coulter counter system for suspension cultures and radiolabelled intracellular markers for substratum-attached, monolayer cultures are presented. The advantages, limitations, and conditions under which the different methods can be used are discussed. It is pointed out that there is a need for more direct physical methods for measuring dynamic changes in the cell volume of monolayer cultures without removing the cells from the substratum. Data from a method applicable to such cultures that measures extracellular impedance are presented. PMID- 1295684 TI - Correlations between energy metabolism, ion transport, and water content in astrocytes. AB - Energy metabolism, ion transport, and water content are interrelated in mechanisms of homeostasis of the brain intracellular and extracellular environment. The simplest model of cell homeostasis, the pump-leak hypothesis, incorporates basic relationships between these variables. Although this model accurately calculates steady-state cell volumes, ion concentrations, and metabolic rates, it fails to predict dynamic changes in these properties during elevated extracellular potassium, metabolic inhibition, and osmotic swelling. We have investigated relationships between ions, energy metabolism, and water content in cerebral astrocytes cultured from the neonatal rat. These cells swell more in hypoosmotic phosphate-buffered saline (PBS) containing NaCl than in hypoosmotic PBS with all NaCl replaced equiosmotically by sucrose. Unidirectional Na+ influx also is greater in cells suspended in hypoosmotic, compared with isoosmotic PBS. These data suggest that astrocytes possess a cell volume dependent mechanism of Na+ accumulation. The influx of Na+ during swelling may be coupled to metabolism via Na-K ATPase and may contribute to the sustained swelling of astrocytes observed in hypoosmotic swelling of the brain in situ. PMID- 1295685 TI - Role of taurine in neural cell volume regulation. AB - Release of taurine and other amino acids was monitored from cultured astrocytes and neurons under isosmotic and hyposmotic conditions as well as during exposure of the cells to 56 mM KCl. The release was correlated with swelling, as determined by the 3-O-methylglucose method. It was shown that release of taurine from astrocytes cultured from cerebral cortex and cerebellum of rats and mice regardless of the stimulating agent is a consequence of cell swelling. The release is unrelated to depolarization. This conclusion is also valid regarding release of taurine from cerebellar granule neurons. Comparison of release of different amino acids showed that not only taurine but also to some extent glutamate, aspartate, and glycine are released during cell swelling. On the other hand, glutamine is not released under these conditions. Studies of uptake of taurine under isosmotic and hyposmotic conditions as well as the dependency of the release on sodium and temperature strongly suggest that the release process is mediated by diffusional forces and not by a reversal of the high-affinity carrier. It is proposed that taurine may play an important role as an osmotically active substance in the brain involved in cell volume regulation. PMID- 1295686 TI - Involvement of second messengers and protein phosphorylation in astrocyte swelling. AB - In a hypoosmotic model of astrocyte swelling, we found that Ca2+ and intracellular signals such as diacylglycerol and inositol phosphate, as well as protein phosphorylation systems, are implicated in the generation and (or) modulation of volume regulatory processes. Cyclic AMP, which also has a significant effect on astrocyte volume regulation, in addition influences some of these second messengers. PMID- 1295687 TI - Effect of vasopressin on brain swelling at the cellular level: do astrocytes exhibit a furosemide--vasopressin-sensitive mechanism for volume regulation? AB - Two sets of new observations are reported: (i) astrocytes in primary cultures show an increased potassium-induced swelling in the presence of 1-100 x 10(-12) M vasopressin, whereas no similar phenomenon is found in primary cultures of neurons, and (ii) the furosemide-sensitive cotransport system for uptake of K+, Na+, and Cl-, which is known to exist in astrocytes, is absent in neurons. On the basis of these findings and observations by other investigators on transport of ions and water in the brain in vivo, a novel mechanism is suggested, according to which all boundaries of brain parenchymal tissue (perivascular astrocytic end feet, glia limitans, and ependyma) in the absence of vasopressin are capable of performing a net uptake of K+, Na+, and Cl- without uptake of water, and that the resulting hyperosmolarity in the presence of vasopressin leads to water uptake (cell swelling), which causes a reduction in the amount of water in the interstitial fluid and thus an increase in extracellular concentrations of ions. PMID- 1295688 TI - Intracellular transduction mechanisms for the slow synaptic events. AB - Electrical activities of the postganglionic neurons in the superior cervical ganglia of rabbits are modulated in various ways following activation of the subtypes of muscarinic acetylcholine receptors. (i) M1 receptors mediate a slow depolarization consisting of at least three types of ionic conductance changes, and one of these is possibly mediated by cyclic GMP. (ii) M2 receptors mediate a slow hyperpolarization that seems to be generated by inositol triphosphate derived from phosphatidylinositol breakdown. (iii) M2 receptors also cause, through an activation of C kinase, a suppression of Ca entry during action potentials that results in a characteristic change in the action potentials and thereby modulates excitability of superior cervical ganglion neurons. Each subtype of muscarinic receptors thus regulates different pathways of intracellular transduction and modulates the electrical signaling of sympathetic neurons. PMID- 1295689 TI - Synaptic mechanisms in sympathetic preganglionic neurons. AB - Intracellular recordings from sympathetic preganglionic neurons (SPNs) in adult cat and neonatal rat spinal cord slices reveal four types of synaptic potentials, namely, excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and slow EPSPs in both preparations, and a slow IPSP in cat SPNs. Pharmacological studies show that glutamate or a related excitatory amino acid and glycine are the probable mediators of EPSPs and IPSPs. There may be heterogenous mediators of slow EPSPs; substance P, serotonin, norepinephrine, and epinephrine are all probable mediators of slow EPSPs in subpopulations of SPNs. In the case of slow IPSPs, norepinephrine appears to be the likely transmitter. Finally, stimulation of ventral roots elicits a synaptic potential that appears to be caused by glutamate released from afferent fibers in the ventral roots. Our results indicate that a multitude of synaptic mechanisms exist in the rat SPNs by means of which inputs arising from sensory and supraspinal neurons are processed in a timely and orderly manner, thus ensuring highly organized but differentiated outputs to multiple peripheral target cells. PMID- 1295691 TI - Clinical aspects of chronic urticaria. PMID- 1295690 TI - The pathophysiology of chronic urticaria. PMID- 1295693 TI - Small GTP-binding proteins on rat liver lysosomal membranes. AB - GTP-binding proteins have been identified on the membranes of highly purified dextran-filled lysosomes (dextranosomes) and Triton-filled lysosomes (tritosomes) obtained from rat liver. Autoradiography of blots of lysosomal membrane proteins incubated with [alpha-32P]GTP revealed the presence of several specific GTP binding proteins with a relative molecular mass (M(r)) predominantly in the range of 26-30 kDa. These GTP-binding proteins migrated slower in polyacrylamide gels than purified c-Ha-ras protein expressed in E. coli, whose apparent M(r) was 23 kDa in the same blot. The relative contents of GTP-binding proteins in lysosomal membranes were comparable or greater than that of plasma membranes and of microsomes. Chemical extraction showed that lysosomal GTP-binding proteins were more tightly associated with the membranes than with microsomal GTP-binding proteins. The possible involvement of lysosomal GTP-binding proteins in cellular functions including vacuolar (lysosomal) acidification and organellar dynamics are discussed. PMID- 1295692 TI - Contact urticaria (immediate reaction syndrome). PMID- 1295695 TI - Calcium-sensitive, actin-related gelation of cell extracts of thermosensitive Chinese hamster lung cells capable of anchorage-independent growth. AB - The extent of actin-related gelation of extracts of thermosensitive Chinese hamster lung (CHL) cells capable of anchorage-independent growth was studied quantitatively by monitoring the total protein in the gel obtained by low-speed centrifugation. The gelation depended on the presence of ATP, KCl, MgCl2, and a reducing agent. Micromolar concentrations of Ca2+ and low doses of cytochalasin B inhibited the actin-related gelation of these extracts. The gelation was more sensitive to inhibition by Ca2+ and cytochalasin B when the extracts were prepared from cells cultured at the permissive rather than the nonpermissive temperature. When various ts mutants were examined, the half-maximal inhibitory dose (HMID) of Ca2+ and cytochalasin B for gelation of extracts of cells cultured at the nonpermissive temperature was between 1.25 and 2.19 times higher than that for extracts of the same cells cultured at the permissive temperature. The values of the HMID for Ca2+ and cytochalasin B changed shortly after the shift in temperature of cell cultures from the nonpermissive to permissive temperature. When cell extracts were incubated at the permissive temperature in vitro for only 15 minutes, these changes in values of HMID were also observed. Analysis of polypeptides of cell extracts and gel pellets on polyacrylamide gel electrophoresis suggested that the decrease in amount of a high-molecular-weight actin-binding protein (250 kDa) may play an essential role in the increased sensitivity to inhibition by Ca2+ and cytochalasin B of actin-related gelation in extracts of these ts mutants. PMID- 1295694 TI - Entrainment to external Ca2+ oscillation in ionophore-treated Physarum plasmodium. AB - To elucidate the mechanism of mutual interaction between intracellular chemical rhythms in the Physarum plasmodium, external Ca2+ oscillation was applied to the ionophore-treated plasmodial strand and its response was measured as tension oscillation. (i) Tension oscillation is entrained and phase locked to the externally applied Ca2+ oscillation. (ii) Two kinds of stable phase relationship, in-phasic and anti-phasic ones, are observed between them. (iii) Transition between the two stable phase relationships is also observed. These results suggest that intracellular rhythms with control tension generation are mutually entrained by means of cytosolic Ca2+ oscillation in the organism and that their interactions have two kinds of stable phase relationships. PMID- 1295696 TI - Correlation of axenic linkage groups with the position of the microtubule organizing center in aggregating Dictyostelium. AB - Positioning of the microtubule-organizing center (MTOC) in Dictyostelium discoideum was found to be genetically regulated. We examined the wild-type strain NC-4 cells independently maintained in different laboratories, freshly recovered cells from spores stocked for over 20 years, the temperature-sensitive growth mutant HU49 isolated from NC-4, as well as strain V-12 which is the opposite mating-type to NC-4. During aggregation on nonnutrient agar plates, all these strains showed similar cell polarity, as defined by the alignment of the nucleus ahead of the MTOC. By contrast, in Ax2 and Ax3, axenic strains carrying axenic mutations on linkage groups II and III, the MTOC was usually positioned ahead of the nucleus. Cells containing axenic linkage group II but not III positioned the MTOC ahead of the nucleus. Conversely cell polarity of strains including axenic linkage group III but not II was similar to that of wild-type cells. Thus axenic linkage group II, probably axeC or other linked gene(s) not yet identified, is responsible for the location of the MTOC anterior to the nucleus during aggregation. The anterior positioning of the MTOCs was prevented by growth on bacteria in cells carrying both axenic linkage groups, but not in those carrying only axenic linkage group II. PMID- 1295697 TI - Alternatively-spliced p53 mRNA in the FAA-HTC1 rat hepatoma cell line without the splice site mutations. AB - A novel mutation of the p53 gene has been found in a rat hepatoma cell line, FAA HTC1. This cell line carried two kinds of abnormal p53 transcripts; one lacked the exon 8 sequence, and the other had a single base substitution G to T which resulted in a new stop codon in exon 8. In the genomic DNA, this base substitution in exon 8 was present, indicating that both transcripts were transcribed from the mutated gene. No mutation was detected in its two flanking introns. In this cell line, the exon-deleted transcript seems to be generated by exon skipping due to an unknown mechanism other than splice site mutations. PMID- 1295698 TI - Inhibition of expression of a mouse alpha-globin gene by plasmids that include antisense oligonucleotides. AB - Plasmid-borne DNAs, corresponding to 68-base oligodeoxynucleotides, synthesized in the antisense or sense configuration and based on the nucleotide sequences of various regions of the mouse alpha-globin mRNA, were introduced with the gene for xanthine-guanine phosphoribosyl transferase from E. coli (Ecogpt) into mouse erythroleukemia (MEL) cells by protoplast fusion. Specific inhibition of the synthesis of alpha-globin was observed only in the cells transformed with the plasmids with antisense 68-mers that corresponded to the cap site as well as the site of initiation of translation of alpha-globin mRNA (Oligo-A); Other plasmids with antisense 68-mers that corresponded to the regions of the exon/intron junctions, the individual exons, or the 3' untranslated region were ineffective. This antisense RNA efficiently reduced the production of alpha-globin to 9-18% of the endogenous level after induction with hexylmethylene-bis-acetoamide (HMBA). Moreover, most of the antisense transformants did not show any decrease in the expression of the c-myc gene at the early phases of differentiation of MEL cells. Thus, we propose a hypothesis that the early decline in levels of c-myc mRNA may be independent of and uncoupled from the program of globin synthesis during the differentiation of MEL cells. PMID- 1295699 TI - [Immunochemical changes in the outer membrane of Escherichia coli adapted to amine oxides]. AB - Resistant strains of Escherichia coli were obtained by stepwise cultivation in subinhibitory concentrations of two antimicrobially active amine oxides. Changes in the chemical composition of the outer membrane of the resistant strains were accompanied also by different antigenic reactions. New precipitation lines were revealed by double immunodiffusion and immuno-electrophoretic methods. The results of immunochemical analysis confirm the findings that the resistance to amphiphilic compounds is associated with the outer membrane which limits the access of antimicrobially active molecules to their sites of action in the cytoplasmic membrane. PMID- 1295701 TI - [Induction of enzymes which metabolize substances foreign to the body and possible mechanisms of their effect]. PMID- 1295700 TI - [Local anesthetics. CVII. Local anesthetic effects of phenylcarbamates--the effect of connecting chain modification]. AB - The preceding study of the effect of the branching of the connecting chain by the metoxymethyl-, ethoxymethyl- and propoxymethyl group on the alpha carbon on local anaesthetic activity was a stimulus for the preparation of 16 drugs of the group of 1-ethoxyethoxymethyl-2-(1-pyrrolidinyl-), 2-piperidino- and 2-(1 perhydroazepinyl) ethyl esters of o-, m- and p-alkoxyphenylcarbamic acids. The discontinuation of the substituent on the alpha carbon of the connecting chain by another oxygen atom (introduction of an ethoxyethoxymethyl group) has a positive effect on surface and infiltration anaesthesia. Of the prepared agents, 2 piperidino- and 2-(1-perhydroazepinyl-) derivatives with a hexyl or heptyloxy group in the o-position of the benzene ring were most effective; they exceeded the standards cocaine and procaine more than one hundred times. p-Derivatives were least effective; in some cases their indices of effectiveness did not achieve the effectiveness of the standards in both surface and infiltration anaesthesia under study. Acute toxicity of all drugs lies within the range of the toxicities of the standards. PMID- 1295702 TI - [Medication errors from the legal aspect]. PMID- 1295703 TI - Diagnostic and therapeutic advances in nephrology. October 26-29, 1991, Madrid. Proceedings of a symposium. PMID- 1295704 TI - The role of NAG (N-acetyl-beta-D-glucosaminidase) in the diagnosis of kidney disease including the monitoring of nephrotoxicity. AB - The assay of urinary N-acetyl-beta-D-glucosaminidase (NAG) provides an early indication of tubular dysfunction resulting from renal disease or nephrotoxic damage. False positives are rare and its activity remains high during active disease or a sustained toxic insult but falls to normal levels on recovery or removal of the toxin. Urinary NAG activity can be used in conjunction with other tests to assess disease activity and prognosis. The assay of NAG isoenzymes increases the diagnostic potential of this test while the availability of dipsticks and simple assay kits will allow its use outside the laboratory. PMID- 1295705 TI - Microalbuminuria in non-insulin-dependent diabetes. AB - According to international consensus, microalbuminuria is defined as an elevated urinary albumin excretion rate (UAER) of 20-200 micrograms/min, which is below the proteinuric range. Nephropathy is a major complication in IDDM, seen in about 30% of patients after many years of diabetes. Increasing microalbuminuria is an excellent marker of subsequent nephropathy in these patients. End-stage diabetic nephropathy is also important in NIDDM, but in most Western countries this serious complication eventually develops in only 5 to 10% of cases, whereas the majority of patients die before this from cardiovascular disease. In completely healthy individuals there is no clear correlation between age and UAER, at least up to about 70 years of age. The mean excretion rate is around 5 micrograms/min, with a considerable range, but excretion only rarely exceeds 15 micrograms/min. In population studies among middle-aged and elderly individuals, higher values are seen. In newly diagnosed NIDDM about 40% of patients show an excretion rate above 15-20 micrograms/min. There is a significant but not precise correlation between albumin excretion rate and glycemic control, and usually UAER is reduced by standard antidiabetic treatment. In a considerable number of patients, high values cannot be reduced. In the course of NIDDM about 20-30% of patients show microalbuminuria. In patients with known diabetes, microalbuminuria is related not only to subsequent diabetic proteinuria, but even more strongly to early death, mainly from cardiovascular disease. Even slight microalbuminuria (15-40 mg/l in early morning urines) is clearly associated with increased mortality. In subjects with newly detected elevated blood glucose (by screening) microalbuminuria also predicts early mortality. The mechanisms are not established, but several arteriosclerosis-related risk factors are seen more frequently in patients with microalbuminuria, e.g. lipid abnormalities, elevated systolic blood pressure (BP), hemostatic measures, as well other markers of cardiovascular disease. Usually there is a significant but not precise correlation between BP and UAER in groups of patients throughout the course of diabetes. New studies document that also in the elderly background population microalbuminuria is a significant risk factor for early death, maybe even stronger than the established risk markers, which thus may be confounded with the presence of microalbuminuria. PMID- 1295706 TI - Markers for the diagnosis and monitoring of renal tubular lesions. AB - Single proteins and tubular enzymes have been proposed as markers to detect and differentiate prerenal, glomerular, tubular and postrenal forms of proteinuria and hematuria. By quantitation of total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin and N-acetyl-beta,D-glucosaminidase (beta-NAG) activity it has become possible to clearly separate these forms by analysis of a single sample of second morning urine. When this program was applied to screening of hospital patients, albumin, total protein and NAG proved to be sufficient to exclude clinically relevant disturbances. alpha 1-Microglobulin was useful to separate primary glomerulopathies from tubulo-interstitial diseases. Glomerular and postrenal hematuria could be clearly separated by their different excretion rates of alpha 2-macroglobulin, if urine albumin concentration exceeds 100 mg/l. The results imply that wider application of these techniques can help to detect renal abnormalities at an earlier stage and differentiate their various forms by less invasive techniques. PMID- 1295707 TI - Albuminuria of hypertensive patients. AB - Renal dysfunction as a consequence of malignant hypertension has been recognized for decades in patients with essential hypertension. It has been shown only recently, however, that albuminuria (including underlying albuminuria not detectable by conventional tests, i.e. microalbuminuria) has emerged as a frequent sequela of essential hypertension. Furthermore, renal dysfunction of the elderly as a result of ischemic nephropathy, in the absence of malignant hypertension, has turned out to be an important long-term outcome in the patient with essential hypertension. The presence of albuminuria is a strong predictor of cardiovascular events. Albuminuria is associated with more severe hypertension and with evidence of more advanced target organ damage (e.g. LVH). It is more prevalent in the elderly. It is unknown whether the predictive value of albuminuria reflects its association with more severe hypertension and end-organ damage, or whether albuminuria serves as an indicator of capillary leakiness which causes detectable abnormalities in the renal microcirculation but reflects more generalized endothelial barrier dysfunction predisposing to accelerated atherogenesis. PMID- 1295708 TI - Present status of kidney transplantation. AB - Kidney transplantation today is the method of choice to treat end-stage renal disease (ESRD) in more than 50% of the ESRD-population. Due to major improvements in surgical handling, immunosuppressive therapy, and infection control, the one year survival for patients and first grafts has reached nearly 90% in the recent years. In contrast no comparable achievements have been made in long-term graft survival. A constant number of grafts is lost yearly after the first postoperative year. In addition an increasing number of well functioning grafts is lost due to the death of the recipients caused mainly by cardiovascular and malignant disorders. The extension of kidney transplantation to all suitable recipients is nearly exclusively hampered by the organ shortage, which is further enhanced by failing grafts. This urges us to further improve the prognosis for patient and graft. This must include organ sharing on the basis of improved HLA typing to achieve highly compatible grafts. The tools for differential diagnosis of acute and chronic graft dysfunction have to be improved. New immunosuppressive agents with higher immunosuppressive power and specificity but fewer nephrotoxic, metabolic and hemodynamic side effects are required at least for chronic rejection. The risk of infectious and malignant complications must be limited. PMID- 1295709 TI - Selective immunosuppression with anti-T cell monoclonal antibodies. AB - Murine monoclonal antibodies specifically directed at the CD3 molecular complex are widely used in clinical practice. They are potent inhibitors of immune function and may be administered in association to conventional immunosuppressants. The main purpose of this review is to summarize our present knowledge on the CD3 molecule, to discuss the available data on the clinical use of anti-CD3 MoAb (therapeutic effectiveness, mode of action and side effects) and the recent information derived from the use of anti-CD3 MoAb in experimental models that are opening new perspectives in the applications of anti-CD3 and will hopefully lead to the extension of its clinical use to settings different from transplantation. PMID- 1295710 TI - Nephrology clinical trials supported by the kidney programs of the National Institutes of Health. PMID- 1295711 TI - The place of loop diuretics in the treatment of acute and chronic renal failure. AB - Loop diuretics (furosemide, bumetanide, muzolimine, piretamide, torasemide) are powerful drugs capable of increasing sodium excretion and urine output even when renal function is markedly impaired. In patients with chronic renal failure (CRF), loop diuretics may be given to control extracellular volume (ECV) expansion responsible for hypertension. But the use of loop diuretics in chronic uremia is mostly helpful when impaired renal function co-exists with nephrotic syndrome or chronic heart failure. Due to their powerful natriuretic activity, loop diuretics have been administered also to patients on maintenance dialysis to reduce the frequency of and/or to curtail dialysis time. In this condition, however, the increase of sodium and water excretion is very limited; whereas the use of diuretics in high dosage is not devoid of risky side effects such as neurologic lesions, cramps, deafness, weakness, muscle pain. In some patients with oliguric form of acute renal failure (ARF), loop diuretics increase sodium excretion and urine output. They do not affect the mortality rate for ARF but may facilitate the treatment of patients by reverting an oliguric form to a non oliguric form of ARF. PMID- 1295712 TI - Effect of antihypertensive therapy on the progression of non-diabetic renal disease. AB - There is a clear, inverse association between the level of blood pressure and the progression of renal disease. This association appears to extend well within the "normotensive" blood pressure range. Currently, there are no absolutely incontrovertible data from prospective, randomized trials in humans documenting that high blood pressure is the cause of an accelerated loss of GFR, or that the loss in renal function can be prevented by lowering blood pressure below 140/90 mmHg. Nevertheless, an aggressive lowering of blood pressure in patients with hypertension and renal disease seems reasonable and desirable. First, the control of blood pressure lowers the "all causes" risk of cardiovascular morbidity and mortality in all patients with elevated blood pressure. Second, any detrimental effects on GFR are uncommon or transient in these patients. Third, the beneficial effects on GFR are firmly supported in animal studies and in humans with malignant hypertension. Fourth, a growing body of evidence from human trials supports the inverse correlation between blood pressure and decrease in GFR, even below a level of 140/90 mmHg. The evidence for these conclusions is reviewed. PMID- 1295713 TI - The possible use of bisphosphonates in the treatment of renal osteodystrophy. AB - Bisphosphonates appear to provide an attractive, novel approach in the management of patients with uremic bone disease. Only limited studies are available. Based on the understanding of the pathogenesis of renal bone disease, three major indications for the use of bisphosphonates in patients with uremic bone disease emerge: 1. Hypercalcemia related to increased release of calcium from bone. 2. Excessive elevation of bone turnover related to increased parathyroid hormone effects. 3. Extraosseous calcifications due to high calcium phosphorus product. Moreover, further studies may reveal how the combination between bisphosphonates and 1,25 vitamin D therapy might affect uremic bone. Details on doses, mode of administration (continuously vs. intermittently) and optimal duration of therapy should be tested in an animal model of uremic bone disease. PMID- 1295714 TI - Effect of recombinant human erythropoietin on iron balance in maintenance hemodialysis: theoretical considerations, clinical experience and consequences. AB - Iron deficiency is the main reason for insufficient response to rEPO therapy. Serum ferritin and transferrin saturation give valuable information on storage iron and iron transport. Iron demand for correction of anemia can easily be estimated after HCT (vol%) x average blood volume (dl) = mg iron. Inadequate iron supply of the bone marrow in the presence of sufficient storage iron in the RES develops frequently under rEPO, possibly explaining the improvement of bone marrow response to rEPO by concomitant intravenous iron supply. The reasons of functional iron deficiency are still speculative. PMID- 1295715 TI - The long-term effects of recombinant human erythropoietin on the cardiovascular system. AB - Fifty-five hemodialysis patients (pts) received rHuEpo for 3-5 years (51 +/- 11 months, hematocrit 32.5 +/- 3.7). BP medication was required in 42% of pts prior to rHuEpo (Hct 20.8 +/- 3.5) and 69% (38 patients) now require such therapy. BP was controlled with single therapy in 16 pts and only 8 required 3 or more different BP drugs. Vascular access clotting episodes were rare in pts with autologous fistula (17 of 24 pts had no clotting), whereas access clotting episodes were 10 times more common in pts with AV grafts, yet 20% had no clotting after 3-5 years of rHuEpo. Heart size decreased in most who initially had cardiomegaly. Cardiovascular related and other deaths were decreased in this selected group when compared to other dialysis pts matched for age, race and type of renal disease. PMID- 1295716 TI - Stimulatory effect of circulated nicotine on rapidly adapting receptors in canine lungs. AB - The objective of this study was to determine the effect of circulated nicotine on rapidly adapting receptors (RARs) in canine lungs. Afferent activities of RARs were studied with a single fiber recording technique in 10 anesthetized, open chest and artificially ventilated dogs. Bolus injection of nicotine (10 micrograms/kg) into either right or left atrium did not activate the RARs in the first two breaths, but it consistently evoked a mild stimulatory effect beginning approximately 3-6 breaths after the injection, accompanied by a mild increase in tracheal pressure (Pt). There was no significant difference between the receptor responses to nicotine injected via these two different routes in either the peak discharge or the latency time. By contrast, nicotine delivered by cigarette smoke directly into the airways triggered an intense burst of activity upon the very first breath of smoke delivery. Taken together, these results suggest that the sensory endings of RARs are located near the surface of airway epithelium, more easily accessible from the luminal side of the airways. The delayed stimulation of RARs following the nicotine injection was probably activated by the bronchoconstrictive effect of nicotine. PMID- 1295717 TI - Effects of acute exercise on the biosynthesis of eicosanoids in rats. AB - We conducted this study to evaluate the effects of different intensities of acute exercise on the regulation of endogenous eicosanoid levels in male Wistar rats. The animals were divided into 4 groups; i.e.: control, mild exercise, moderate exercise and severe exercise. Immediately after exercise, animals were sacrificed. Plasma prostacyclin (PGI2) level and PGI2 release from two vessel segments (i.e., thoracic aorta and inferior vena cava) were determined by a specific 6-keto-PGF1 alpha (125I) radioimmunoassay. Urine thromboxane was determined by a specific 11-dehydro-TXB2 (125I) radioimmunoassay and normalized by urine creatinine. Although both plasma PGI2 and urine thromboxane tended to be elevated by severe exercise, only the increase in thromboxane was statistically significant (p < 0.05). In addition, PGI2 release from both vessels were not affected by different intensities of acute exercise. We also observed that aortic PGI2 release was greater than their corresponding veins in each group. We therefore conclude that only severe acute exercise, rather than mild or moderate exercise, may affect prostacyclin-thromboxane balance in rats. PMID- 1295718 TI - Mechanisms of adrenaline-induced antinociception in mice. AB - Infusion of adrenaline into the upper lumbar subarachnoid space in lightly anesthetized mice produced a significant elevation of the nociceptive threshold as quantitated by tail flick test. The antinociceptive effect of adrenaline was dose-dependent and antagonized equally by pretreatment with either alpha-1 selective antagonist prazosin or alpha-2 selective antagonist yohimbine at a dose of 0.05 microgram/5 microliter/mouse. This antinociceptive effect of adrenaline was also blocked by pretreatment with beta antagonist propranolol or opiate antagonist naloxone at higher doses, i.e., 0.5 microgram and 1.0 microgram/5 microliter/mouse, respectively. These results suggest that the antinociceptive mechanisms of adrenaline at the lumbar spinal level in the mouse seem to be mediated not only through alpha- and beta-adrenergic pathways but also through opiate system. PMID- 1295719 TI - Localization of the sympathetic postganglionic neurons innervating cardiac coronary artery with horseradish peroxidase in monkeys. AB - Localization of the sympathetic postganglionic neurons innervating the cardiac coronary arteries in monkeys was investigated by using retrograde axonal transport of horseradish peroxidase (HRP). HRP was applied to the main trunk of the left and right coronary arteries, and to the terminal branches of the ventral and dorsal descending vessels of the left and right coronary arteries, respectively. The animals were sacrificed 84-96 hours later and perfused via the left ventricle. The paravertebral sympathetic ganglia from the superior cervical, middle cervical and stellate ganglia to the T9 ganglia, and nodose ganglia were removed and processed for HRP identification. After HRP was applied into the main trunk of the right coronary artery, and into the main trunk and the terminal branches of the descending vessels of the left coronary artery, the HRP-labeled sympathetic neurons were localized predominantly in the right superior cervical ganglion, and next in the left superior cervical ganglia. However, labeled cells were found in the stellate ganglia bilaterally. After HRP applications to the terminal branches of the dorsal descending vessels of the right coronary artery, HRP-labeled cells were mainly present in the left superior cervical ganglion and next in the right superior cervical ganglion. Some labeled cells were found in the middle cervical and stellate ganglia. No labeled cell was found in ganglia below the second thoracic ganglia on either side in these four groups. PMID- 1295720 TI - New anti-inflammatory antedrugs: steroid acid esters and amides. AB - Therapeutic use of anti-inflammatory steroids is limited, due primarily to their suppressive effects on pituitary function and the immune system. In an attempt to circumvent the untoward systemic effects of corticosteroids, a new approach, the antedrug concept, was formulated by Lee. The term "antedrug" describes a drug that is active upon local application but is easily biotransformed, on entry into the systemic circulation, to an inactive or much less active metabolite. Thus, an antedrug acts only locally at the site of application and produces minimal systemic effects. This report provides a synopsis of the "evolution" of steroidal antedrugs, containing a metabolically labile carboxamide moiety, on the side chain or at the C-16 position of prednisolone. Pharmacological screening of these steroidal antedrugs in the rat cotton pellet and croton oil-induced ear oedema bioassays led to the identification of P16CM, 11, as the lead compound and a viable drug candidate. PMID- 1295721 TI - Characterization of zidovudine resistant variants of HIV-1 isolated from patients on prolonged therapy. AB - As part of a clinical trial to assess zidovudine related toxic effects, the authors followed 48 initially asymptomatic individuals who received prolonged therapy with this drug at several tertiary care institutions. Blood samples had been obtained for viral isolation every three months and had yielded infectious HIV-1 progeny in over 94 percent of cases. After one year of therapy, over 30 percent of individuals had developed variants of HIV-1 that displayed in vitro resistance to zidovudine. Six of these zidovudine resistant variants of HIV-1 were compared with drug sensitive isolates obtained from the same subjects prior to initiation of treatment. The drug resistant variants were generally as infectious per mg viral protein for both susceptible T cell lines and peripheral blood mononuclear cells as the corresponding parental isolates from which they were derived. The drug resistance phenotype remained stable, in that zidovudine insensitive species could still be identified, following many replication cycles in the absence of drug pressure. However, the percentage of zidovudine resistant viruses appeared to diminish in culture over time under such conditions. This was demonstrated by the fact that lower percentages of cells became infected in the presence of the drug, if the viruses used for infection had been propagated in the absence of the drug. In addition, higher concentrations of such viruses were required to initiate infection in the presence of the drug, and these viruses possessed lower IC50's for zidovudine. This suggests that zidovudine resistant variants of HIV-1 may be unlikely to possess any growth advantage in the absence of the drug. PMID- 1295722 TI - Activity of vancomycin against recently isolated nosocomial gram-positive cocci. AB - This study reports the in vitro activity of vancomycin against 174 Gram-positive cocci isolated in nosocomial patients. Vancomycin was shown to have a slightly better activity than teicoplanin and was the most active of all other agents tested including imipenem, new quinolones and aminoglycosides. PMID- 1295723 TI - Penetration of fleroxacin into human lung, muscle, and fat tissue. AB - Fleroxacin is a new fluoroquinolone with established potent antimicrobial and pharmacokinetic properties, and the aim of this study was to determine its rate of penetration into human lung, muscle, and fat tissues. In a total of eight patients undergoing lung surgery, plasma and tissue concentrations of unmetabolized fleroxacin were determined. This was done in subgroups of two patients each, receiving either 6, 8, 12 or 24 hours prior to surgery one single oral dose of 400 mg fleroxacin. It was found that fleroxacin penetrates well into muscle and lung tissues, but not into fat tissue. The levels in muscle and lung were 1.1 to 4.7 times higher than the according plasma concentrations. PMID- 1295724 TI - A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects. AB - Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295725 TI - Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis. AB - We found that E-cadherin (uvomorulin) is transiently expressed in restricted regions of the metencephalon, mesencephalon and diencephalon of mouse embryonic brain. This expression first occurred in parts of the mesencephalon and diencephalon at around E9.5, and subsequently extended to the primordia of cerebellum, the dorsal midline of mesencephalon and some other regions of the embryonic brain. These E-cadherin expressions ceased by E15 except at the dorsal midline. Immunohistological analyses showed that E-cadherin-positive cells are radially arranged in the neural tube and the E-cadherin-positive regions are sharply demarcated from E-cadherin-negative regions. Axons extending from some of the E-cadherin-positive regions also expressed this molecule. When embryonic brains were dissociated into single cells and cultured as monolayers, E-cadherin positive cells formed clusters that were segregated from E-cadherin-negative cells. E9.5 brain fragments containing metencephalon and mesencephalon were isolated, explanted on Nucleopore filters and cultured in the absence or presence of antibodies to E-cadherin. This antibody treatment removed most of the E cadherin molecules from the explants and consequently affected their growth pattern. To analyze cellular events induced by the antibody treatment, we stained these explants with an antiserum to En whose distribution was found to overlap in part with that of E-cadherin and found that the pattern of En staining was altered by the anti-E-cadherin antibody treatment. These results suggest that the local and transient expression of E-cadherin in embryonic brain is involved in regional pattern formation in this organ. PMID- 1295727 TI - Isolation of Sna, a mouse gene homologous to the Drosophila genes snail and escargot: its expression pattern suggests multiple roles during postimplantation development. AB - The Drosophila gene snail encodes a zinc-finger protein that is required zygotically for mesoderm formation. Snail acts as a transcriptional repressor during the period of mesoderm formation by preventing expression of mesectodermal and ectodermal genes in the mesoderm anlage. A Xenopus homolog (xsnail) of snail has been cloned and it too is expressed early in the mesodermal germ layer. We have isolated cDNA clones of a mouse gene (termed Sna) closely related to snail and xsnail and another Drosophila gene termed escargot that also encodes a zinc finger protein. Sna encodes a 264 amino acid protein that contains four zinc fingers. Developmental RNA blot analysis showed that Sna transcripts are expressed throughout postimplantation development. Analysis of the spatial and temporal localization of Sna transcripts by in situ hybridization to both whole mount and sectioned embryos revealed that, in the gastrulating embryo, Sna is expressed throughout the primitive streak and in the entire mesodermal germ layer. By 9.5 days post coitum (dpc) Sna is expressed at high levels in cephalic neural crest and limb bud mesenchyme. In fact, by 10.5 dpc Sna expression is observed in most mesenchymal cells, whether of neural crest or mesodermal origin. Later in gestation, high levels of Sna expression are observed in condensing cartilage and in the mesenchymal component of several tissues (lung, kidney, teeth and vibrissae) that undergo epithelial-mesenchymal inductive interactions during development. These results suggest multiple roles for the Sna gene in gastrulation and organogenesis during murine development. PMID- 1295726 TI - The protein product of the zebrafish homologue of the mouse T gene is expressed in nuclei of the germ ring and the notochord of the early embryo. AB - Embryos mutant for the T gene, in mice, make insufficient mesoderm and fail to develop a notochord. We report the cloning and sequencing of the T gene in the zebrafish (Brachydanio rerio) and show the nuclear localization of the protein product. Both RNA and protein are found in cells of the germ ring, including enveloping layer cells, prior to and during gastrulation of zebrafish embryos. Nuclei of the yolk syncytial layer do not express Zf-T. High levels of expression are maintained throughout early development in the notochord, while in paraxial mesoderm cells the gene is turned off during gastrulation. Exposure of animal cap cells to activinA induces Zf-T expression, as does transplantation into the germ ring. PMID- 1295728 TI - In situ hybridization reveals co-expression of embryonic and adult alpha globin genes in the earliest murine erythrocyte progenitors. AB - Murine erythropoiesis begins with the formation of primitive red blood cells in the blood islands of the embryonic yolk sac on day 7.5 of gestation. By analogy to human erythropoiesis, it has been thought that there is a gradual switch from the exclusive expression of the embryonic alpha-like globin (zeta) to the mature adult form (alpha) in these early mouse cells. We have used in situ hybridization to assess expression of these two globin genes during embryonic development. In contrast to what might have been expected, we find that there is simultaneous expression of both zeta and alpha genes from the very onset of erythropoiesis in the yolk sac. At no time could we detect expression of embryonic zeta globin mRNA without concomitant expression of adult alpha globin mRNA. Indeed, adult alpha transcripts exceed those of embryonic zeta in the earliest red cell precursors. Moreover, the pattern of hybridization reveals co-expression of both genes within the same cells. Even in the fetal liver, which supersedes the yolk sac as the major site of murine fetal erythropoiesis, there is a brief co-expression of zeta and alpha genes followed by the exclusive expression of the adult alpha genes. These data indicate an important difference in hematopoietic ontogeny between mouse and that of human, where zeta expression precedes that of alpha. In addition to resolving the embryonic expression of these globin genes, our results suggest that the embryonic alpha-like globin gene zeta may be physiologically redundant, even during the earliest stages of embryonic development. PMID- 1295730 TI - The role of initial cells in maize anther morphogenesis. AB - The near absence of cell movement in plants makes clonal analysis a particularly informative method for reconstructing the early events of organ formation. We traced the patterns of cell division during maize anther development by inducing sector boundaries that preceded the earliest events of anther initiation. In doing this, we were able to estimate the smallest number of cells that are fated to form an anther, characteristic cell division patterns that occur during anther morphogenesis, and the relationship between the pre-existing symmetry of the initial cells and the final symmetry of the mature anther. Four general conclusions are made: (1) anthers are initiated from small groups of 12 or fewer cells in each of two floral meristematic layers; (2) the early growth of the anther is more like a shoot than a glume or leaf; (3) cell ancestry does not dictate basic structure and (4) the orientation of initial cells predicts the orientation of the four pollen-containing microsporangia, which define the axes of symmetry on the mature anther. The final point is discussed with other data, and an explanation involving a 'structural template' is invoked. The idea is that the orientation of initial cells within the floral meristem establishes an architectural pattern into which anther cells are recruited without regard to their cellular lineages. The structural template hypothesis may prove to be generally applicable to problems of pattern formation in plants. PMID- 1295729 TI - Reduced junctional permeability at interrhombomeric boundaries. AB - Intercellular communication is considered to have a role during pattern specification processes in early embryonic development. This report analyzes the changing gap junctional communication properties of chick neuroepithelial cells depending on their position relative to the segmental partitions of the rhombencephalon. Intercellular electrical coupling and dye transfer were studied with microelectrode techniques. Neuroepithelial cells were electrically coupled irrespective of their location relative to interneuromeric boundaries. Iontophoretic injection of biocytin or Lucifer Yellow into single cells inside the rhombomeres was followed by transjunctional diffusion to the surrounding cells. In contrast, dye transfer was strictly limited when the diffusion zone contacted the cells forming the interneuromeric limits. Label injected into the boundary cells did not spread to other cells at all. Avian interrhombomeric boundaries are thus sites of reduced junctional permeability during early morphogenesis. PMID- 1295731 TI - Epithelial-mesenchymal transformation during palatal fusion: carboxyfluorescein traces cells at light and electron microscopic levels. AB - During the fusion of rodent embryo palatal shelves, the cells of the outer epithelial layer slough off, allowing the cells of the medial edge basal layer to form a midline seam that undergoes epithelial-mesenchymal transformation, as judged by electron microscopy and immunohistochemistry. In this study, we analyze the fate of the transformed cells using a lipid soluble dye to label the medial edge epithelium in situ. Prefusion E14 mouse palates were exposed in vitro or in vivo to a fluoresceinated lipid soluble marker, carboxydichlorofluorescein diacetate succinimidyl ester (CCFSE), which localizes in epithelia as a lipid insoluble compound that does not pass into the connective tissue compartment. The midline seam that formed after 24 hours contained labelled epithelial cells that were replaced by individually labelled mesenchymal cells where the seam transformed. By light microscopy, the labelled cells were seen to contain intensely fluorescent bodies that do not react for acid phosphatase. We were able for the first time to identify these structures by electron microscopy as CCFSE isolation bodies. The cells with isolation bodies are clearly healthy and able to participate in subsequent development of the palate. At 4 days after labelling, individual CCFSE containing cells present in the palate mesenchyme occupy both midline and lateral areas and can clearly be classified as fibroblasts by electron microscopy. CCFSE is a far more useful marker than another lipid soluble marker, DiI, for following cells, because the cells can be fixed and identified both at the light and electron microscope levels. Interestingly, if labelled palatal shelves are not allowed to fuse in vitro, the basal epithelial cells do not form mesenchyme after sloughing, indicating that formation of the epithelial midline seam is necessary to trigger its epithelial-mesenchymal transformation. PMID- 1295732 TI - An axial gradient of transgene methylation in murine skeletal muscle: genomic imprint of rostrocaudal position. AB - We previously used mice bearing a myosin light chain-chloramphenicol acetyltransferase (MLC1-CAT) transgene to show that adult muscle cells bear a heritable, cell autonomous memory of their rostrocaudal position. CAT mRNA and protein are expressed in a > 100-fold rostrocaudal gradient in skeletal muscles of developing and adult MLC1-CAT mice (Donoghue, M. J., Merlie, J. P., Rosenthal, N. and Sanes, J. R. (1991). Proc. Natl. Acad. Sci. USA 88, 5847-5851; Donoghue, M. J., Alvarez, J. D., Merlie, J. P. and Sanes, J. R. (1991). J. Cell Biol. 115, 423-434). Moreover, both in primary cultures and in myogenic cell lines prepared from individual muscles of these mice, CAT levels reflect the body position from which the myoblasts were derived (Donoghue, M.J., Morris-Valero, R., Johnson, Y.R., Merlie, J.P. and Sanes, J. R. (1992). Cell 69, 67-77). Here, we show that the methylation state of the MLC1-CAT transgene in skeletal muscles is also graded along the rostrocaudal axis: methylation levels decrease and expression levels increase in the order, jaw-->neck-->chest and forelimb-->hindlimb. Methylation levels are also approx. 10-fold higher in rostrally derived than in caudally derived myogenic cell lines, which express low and high levels of CAT, respectively. Within each cell line, undifferentiated cells (myoblasts), which do not express the transgene, and differentiated cells (myotubes), which do, are indistinguishable in methylation state. Thus, differentiation-related changes in transgene expression do not affect position-related levels of transgene methylation. On the other hand, treatment of rostrally derived lines with the demethylating agent, 5-azacytidine, decreases methylation and increases expression of the transgene. Thus, perturbation of methylation affects expression. Taken together, these results suggest that methylation provides a genomic imprint of rostrocaudal body position that may serve as a component of the positional memory that mammalian cells retain into adulthood. PMID- 1295733 TI - Cell interactions involved in development of the bilaterally symmetrical intestinal valve cells during embryogenesis in Caenorhabditis elegans. AB - We describe two different cell interactions that appear to be required for the proper development of a pair of bilaterally symmetrical cells in Caenorhabditis elegans called the intestinal valve cells. Previous experiments have shown that at the beginning of the 4-cell stage of embryogenesis, two sister blastomeres called ABa and ABp are equivalent in development potential. We show that cell interactions between ABp and a neighboring 4-cell-stage blastomere called P2 distinguish the fates of ABa and ABp by inducing descendants of ABp to produce the intestinal valve cells, a cell type not made by ABa. A second cell interaction appears to occur later in embryogenesis when two bilaterally symmetrical descendants of ABp, which both have the potential to produce valve cells, contact each other; production of the valve cells subsequently becomes limited to only one of the two descendants. This second interaction does not occur properly if the two symmetrical descendants of ABp are prevented from contacting each other. Thus the development of the intestinal valve cells appears to require both an early cell interaction that establishes a bilaterally symmetrical pattern of cell fate and a later interaction that breaks the symmetrical cell fate pattern by restricting to only one of two cells the ability to produce a pair of valve cells. PMID- 1295734 TI - A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm. AB - Pattern formation in the hindbrain and paraxial mesoderm of vertebrates occurs by the formation of a series of repeated segments. These processes of segmentation appear different at the morphological level, since hindbrain segments, the rhombomeres, form by the subdivision of the neural epithelium into compartments, whereas the mesodermal somites form by the sequential aggregation of mesenchymal cells into epithelial balls. Previous studies have implicated genes encoding transcription factors in the development of hindbrain segments, but nothing is known of genes involved in the formation of somites. Cellular interactions and signal transduction must be an important aspect of hindbrain segmentation, so we have screened for tyrosine kinases expressed in rhombomere-restricted patterns in the developing mouse embryo. We have identified a receptor protein tyrosine kinase, Sek, that has high relative levels of expression in rhombomeres 3 and 5. This alternating pattern is established coincidentally, both spatially and temporally, with the expression of Krox-20, a zinc-finger gene expressed prior to the morphological formation of rhombomeres. In addition, Sek expression occurs in several other developing tissues, including a dynamic regulation in the developing forebrain, spinal cord, early mesoderm and anterior presomitic mesoderm (segmental plate). The latter expression occurs in two stripes that correlate with, and presage, the formation of somites. Sek expression initially occurs throughout the presumptive somite, then becomes restricted anteriorly, and finally is down-regulated as the definitive somite is formed. These data suggest that despite the morphological differences in the segmentation of the hindbrain and mesoderm, Sek is involved in the segmental patterning of both of these tissues. PMID- 1295735 TI - MK: a pluripotential embryonic stem-cell-derived neuroregulatory factor. AB - MK is a gene encoding a secreted heparin-binding polypeptide originally isolated by differential screening for genes induced by retinoic acid (RA) in HM-1 embryonal carcinoma cells. Here we report that MK is expressed at high levels in both embryonal carcinoma and pluripotential embryonic stem cells and their differentiated derivatives. MK expression in these cell types is unaffected by the presence or absence of RA. Recombinant MK protein (rMK) was produced by transient expression in COS cells and purified by heparin affinity chromatography. rMK is a weak mitogen for 10T1/2 fibroblast cells but inactive as a mitogen for Swiss 3T3 fibroblasts. rMK is a potent mitogen for neurectodermal precursor cell types generated by treatment of 1009 EC cells with RA but has no mitogenic or neurotrophic effects on more mature 1009-derived neuronal cell types. rMK is active as an in vitro neurotrophic factor for E12 chick sympathetic neurons and its activity is markedly potentiated by binding the factor to tissue culture plastic in the presence of heparin. Stable 10T1/2 cells lines have been established which express MK. These cells do not exhibit any overt evidence of cell transformation but extracellular matrix preparations derived from these cells are a potent source of MK biological activity. It is concluded that MK is a multifunctional neuroregulatory molecule whose biological activity depends upon association with components of the extracellular matrix. PMID- 1295736 TI - Identification of RNA-binding proteins specific to Xenopus Eg maternal mRNAs: association with the portion of Eg2 mRNA that promotes deadenylation in embryos. AB - Maternal Xenopus Eg mRNAs have been previously identified as transcripts that are specifically deadenylated after fertilization and degraded after the mid blastula transition. Destabilizing cis sequences were previously localised in the 3' untranslated region of Eg2 mRNA. In order to characterize possible trans-acting factors which are involved in the post-transcriptional regulation of Eg mRNAs, gel-shift and u.v. cross-linking experiments were performed, which allowed the identification of a p53-p55 RNA-binding protein doublet specific for the 3' untranslated regions of Eg mRNAs. These p53-p55 proteins do not bind to the 3' untranslated regions of either ornithine decarboxylase or phosphatase 2Ac mRNAs, which remain polyadenylated in embryos. These novel RNA-binding proteins are distinct from the cytoplasmic polyadenylation element-binding protein that controls the polyadenylation of maternal mRNAs in maturing Xenopus oocytes, and from previously identified thermoresistant RNA-binding proteins present in oocyte mRNP storage particles. The p53-p55 bind a portion of the Eg2 mRNA 3' untranslated region, distinct from the previously identified destabilizing region, that is able to confer the postfertilization deadenylation of CAT-coding chimeric mRNAs. This suggests that the p53-p55 RNA-binding proteins are good candidates for trans-acting factors involved in the deadenylation of Eg mRNAs in Xenopus embryos. PMID- 1295737 TI - The function of the neurogenic genes during epithelial development in the Drosophila embryo. AB - The complex embryonic phenotype of the six neurogenic mutations Notch, mastermind, big brain, Delta, Enhancer of split and neuralized was analyzed by using different antibodies and PlacZ markers, which allowed us to label most of the known embryonic tissues. Our results demonstrate that all of the neurogenic mutants show abnormalities in many different organs derived from all three germ layers. Defects caused by the neurogenic mutations in ectodermally derived tissues fell into two categories. First, all cell types that delaminate from the ectoderm (neuroblasts, sensory neurons, peripheral glia cells and oenocytes) are increased in number. Secondly, ectodermal tissues that in the wild type form epithelial structures lose their epithelial phenotype and dissociate (optic lobe, stomatogastric nervous system) or show significant differentiative abnormalities (trachea, Malpighian tubules and salivary gland). Abnormalities in tissues derived from the mesoderm were observed in all six neurogenic mutations. Most importantly, somatic myoblasts do not fuse and/or form an aberrant muscle pattern. Cardioblasts (which form the embryonic heart) are increased in number and show differentiative abnormalities; other mesodermal cell types (fat body, pericardial cells) are significantly decreased. The development of the endoderm (midgut rudiments) is disrupted in most of the neurogenic mutations (Notch, Delta, Enhancer of split and neuralized) during at least two stages. Defects occur as early as during gastrulation when the invaginating midgut rudiments prematurely lose their epithelial characteristics. Later, the transition of the midgut rudiments to form the midgut epithelium does not occur. In addition, the number of adult midgut precursor cells that segregate from the midgut rudiments is strongly increased. We propose that, at least in the ectodermally and endodermally derived tissues, neurogenic gene function is primarily involved in interactions among cells that need to acquire or to maintain an epithelial phenotype. PMID- 1295738 TI - Parental methylation patterns of a transgenic locus in adult somatic tissues are imprinted during gametogenesis. AB - The methylation status of a mouse metallothionein-I/human transthyretin fusion gene was studied during gametogenesis in transgenic mice. In the adult tissues of this mouse line, the promoter region of the transgene on chromosome 11 is methylated when it is maternally inherited and undermethylated when it is paternally inherited. Germ cells from various developmental stages of gametogenesis were isolated, and their DNAs were assayed using methylation sensitive restriction endonucleases and the polymerase chain reaction. Only low to nonexistent levels of transgene methylation were detected in germ cells from 14.5-day-old male and female fetuses irrespective of the parental origin of the transgene. This undermethylated state persisted in oocytes from newborn females as well as in testicular spermatogenic cells and sperm. By contrast, the transgene promoter was completely methylated in fully grown oocytes arrested at the first meiotic prophase. The endogenous metallothionein-I gene promoter, located on a different chromosome, remained undermethylated at all stages examined, consistent with previous findings reported for a typical CpG island. Taken together, the results suggest that parental-specific adult patterns of transgene methylation are established during gametogenesis. PMID- 1295739 TI - Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system. AB - The first step in generating cellular diversity in the Drosophila central nervous system is the formation of a segmentally reiterated array of neural precursor cells, called neuroblasts. Subsequently, each neuroblast goes through an invariant cell lineage to generate neurons and/or glia. Using molecular lineage markers, I show that (1) each neuroblast forms at a stereotyped time and position; (2) the neuroblast pattern is indistinguishable between thoracic and abdominal segments; (3) the development of individual neuroblasts can be followed throughout early neurogenesis; (4) gene expression in a neuroblast can be reproducibly modulated during its cell lineage; (5) identified ganglion mother cells form at stereotyped times and positions; and (6) the cell lineage of four well-characterized neurons can be traced back to two identified neuroblasts. These results set the stage for investigating neuroblast specification and the mechanisms controlling neuroblast cell lineages. PMID- 1295740 TI - Tissue-specific ecdysone responses: regulation of the Drosophila genes Eip28/29 and Eip40 during larval development. AB - The Drosophila genes Eip28/29 and Eip40 are expressed in Kc cells and are rapidly induced by the steroid hormone ecdysone. The molecular basis for Eip28/29's regulation in those cells has been studied in some detail. To determine how this regulation relates to normal development, we have examined the expression of both genes throughout Drosophila development, with special attention to Eip28/29 and the final larval instar. Eip28/29 expression is complex; there are tissues in which it is never expressed, others in which it is continuously expressed at a low level and tissues in which its expression is regulated without obvious relationship to endocrine events. However high-level Eip28/29 expression always correlates with the presence of ecdysone and there is good evidence that Eip28/29 is directly regulated by the hormone in some tissues and at some stages. Most striking are the induction of Eip28/29 transcripts in numerous tissues at the last larval molt, their induction in the epidermis at the time of the 'late 3rd transition', their extinction in the same tissue by the premetamorphic ecdysone peak, and their induction by that peak in the lymph gland, hemocytes and proventriculus. These contrasting regulatory behaviors provide a well-defined model for studying the developmental specificity of steroid responses. Eip40 appears to be ecdysone-inducible only in the lymph gland and there only at the premetamorphic peak. The similarities been Eip28/29 and Eip40 regulation in the lymph gland and Kc cells support the idea that Kc cells are derived from a hematopoietic ancestor. PMID- 1295741 TI - Notochord grafts do not suppress formation of neural crest cells or commissural neurons. AB - Grafting experiments previously have established that the notochord affects dorsoventral polarity of the neural tube by inducing the formation of ventral structures such as motor neurons and the floor plate. Here, we examine if the notochord inhibits formation of dorsal structures by grafting a notochord within or adjacent to the dorsal neural tube prior to or shortly after tube closure. In all cases, neural crest cells emigrated from the neural tube adjacent to the ectopic notochord. When analyzed at stages after ganglion formation, the dorsal root ganglia appeared reduced in size and shifted in position in embryos receiving grafts. Another dorsal cell type, commissural neurons, identified by CRABP and neurofilament immunoreactivity, differentiated in the vicinity of the ectopic notochord. Numerous neuronal cell bodies and axonal processes were observed within the induced, but not endogenous, floor plate 1 to 2 days after implantation but appeared to be cleared with time. These results suggest that dorsally implanted notochords cannot prevent the formation of neural crest cells or commissural neurons, but can alter the size and position of neural crest derived dorsal root ganglia. PMID- 1295742 TI - The epithelium of the dorsal marginal zone of Xenopus has organizer properties. AB - We have investigated the properties of the epithelial layer of the dorsal marginal zone (DMZ) of the Xenopus laevis early gastrula and found that it has inductive properties similar to those of the entire Spemann organizer. When grafts of the epithelial layer of the DMZ of early gastrulae labelled with fluorescein dextran were transplanted to the ventral sides of unlabelled host embryos, they induced secondary axes composed of notochord, somites and posterior neural tube. The organizer epithelium rescued embryos ventralized by UV irradiation, inducing notochord, somites and posterior neural tube in these embryos, while over 90% of ventralized controls showed no such structures. Combinations of organizer epithelium and ventral marginal zone (VMZ) in explants of the early gastrula resulted in convergence, extension and differentiation of dorsal mesodermal tissues, whereas similar recombinants of nonorganizer epithelium and the VMZ did none of these things. In all cases, the axial structures forming in response to epithelial grafts were composed of labelled graft and unlabelled host cells, indicating an induction by the organizer epithelium of dorsal, axial morphogenesis and tissue differentiation among mesodermal cells that otherwise showed non-axial development. Serial sectioning and scanning electron microscopy of control grafts shows that the epithelial organizer effect occurs in the absence of contaminating deep cells adhering to the epithelial grafts. However, labelled organizer epithelium grafted to the superficial cell layer contributed cells to deep mesodermal tissues, and organizer epithelium developed into mesodermal tissues when deliberately grafted into the deep region. This shows that these prospective endodermal epithelial cells are able to contribute to mesodermal, mesenchymal tissues when they move or are moved into the deep environment. These results suggest that in normal development, the endodermal epithelium may influence some aspects of the cell motility underlying the mediolateral intercalation (see Shih, J. and Keller, R. (1992) Development 116, 901-914), as well as the tissue differentiation of mesodermal cells. These results have implications for the analysis of mesoderm induction and for analysis of variations in the differentiation and morphogenetic function of the marginal zone in different species of amphibians. PMID- 1295743 TI - Cell motility driving mediolateral intercalation in explants of Xenopus laevis. AB - In Xenopus, convergence and extension are produced by active intercalation of the deep mesodermal cells between one another along the mediolateral axis (mediolateral cell intercalation), to form a narrower, longer array. The cell motility driving this intercalation is poorly understood. A companion paper shows that the endodermal epithelium organizes the outermost mesodermal cells immediately beneath it to undergo convergence and extension, and other evidence suggests that these deep cells are the most active participants in mediolateral intercalation (Shih, J. and Keller, R. (1992) Development 116, 887-899). In this paper, we shave off the deeper layers of mesodermal cells, which allows us to observe the protrusive activity of the mesodermal cells next to the organizing epithelium with high resolution video microscopy. These mesodermal cells divide in the early gastrula and show rapid, randomly directed protrusive activity. At the early midgastrula stage, they begin to express a characteristic sequence of behaviors, called mediolateral intercalation behavior (MIB): (1) large, stable, filiform and lamelliform protrusions form in the lateral and medial directions, thus making the cells bipolar; (2) these protrusions are applied directly to adjacent cell surfaces and exert traction on them, without contact inhibition; (3) as a result, the cells elongate and align parallel to the mediolateral axis and perpendicular to the axis of extension; (4) the elongate, aligned cells intercalate between one another along the mediolateral axis, thus producing a longer, narrower array. Explants of essentially a single layer of deep mesodermal cells, made at stage 10.5, converge and extend by mediolateral intercalation. Thus by stage 10.5 (early midgastrula), expression of MIB among deep mesodermal cells is physiologically and mechanically independent of the organizing influence of the endodermal epithelium, described previously (Shih, J. and Keller, R. (1992) Development 116 887-899), and is the fundamental cell motility underlying mediolateral intercalation and convergence and extension of the body axis. PMID- 1295744 TI - Patterns of cell motility in the organizer and dorsal mesoderm of Xenopus laevis. AB - In a companion paper (Shih, J. and Keller, R. (1992) Development 116, 901-914), we described a sequence of cell behaviors, called mediolateral intercalation behavior (MIB), that produces mediolateral cell intercalation, the process that drives convergence and extension of the axial and paraxial mesoderm of Xenopus. In this paper, we describe the pattern of expression of MIB in the mesoderm during gastrulation, using video image processing and recording of cell behavior in 'shaved', open-faced explants of the marginal zone. At midgastrula stage (10.5), MIB begins at two dorsolateral sites in the prospective anterior mesoderm and progresses medially along two arcs that lengthen toward and meet at the midline to form a single arc of cells expressing MIB, called the vegetal alignment zone (VgAZ). The notochordal-somitic mesodermal boundary forms within the VgAZ at stage 11, and then progresses animally and laterally, along the prospective anterior-posterior axis, eventually bounding a trapezoidal area the shape of the fate-mapped notochord. Meanwhile, from its origin in the VgAZ, MIB spreads in the prospective posterior direction along the lateral boundaries of both the notochordal and somitic mesoderm. From there it spreads medially in both tissues. Subsequently, vacuolation of notochord cells, and segmentation and expression of a somite-specific marker repeat the progression of mediolateral intercalation behavior. Thus cells in the posterior, medial regions of the notochordal and the somitic territories are the last to express mediolateral intercalation behavior and subsequent tissue differentiations. In explants that do not converge, these cells neither express mediolateral intercalation behavior nor differentiate. These facts suggest that progressions of MIB in the anterior posterior and lateral-medial directions may be organized by signals emanating from the lateral somitic and notochordal boundaries. These signals may have limited range and may be dependent on convergence, driven by mediolateral cell intercalation, to bring cells within their range. In the embryo, the posterior progression of MIB results in arcs of convergence, anchored in the vegetal endoderm at each end, acting on the inside of the blastoporal lip to produce involution of the IMZ. PMID- 1295745 TI - Notch2: a second mammalian Notch gene. AB - Notch is a cell surface receptor that mediates a wide variety of cellular interactions that specify cell fate during Drosophila development. Recently, homologs of Drosophila Notch have been isolated from Xenopus, human and rat, and the expression patterns of these vertebrate proteins suggest that they may be functionally analogous to their Drosophila counterpart. We have now identified a second rat gene that exhibits substantial nucleic and amino acid sequence identity to Drosophila Notch. This gene, designated Notch2, encodes a protein that contains all the structural motifs characteristic of a Notch protein. Thus, mammals differ from Drosophila in having more than one Notch gene. Northern and in situ hybridisation analyses in the developing and adult rat identify distinct spatial and temporal patterns of expression for Notch1 and Notch2, indicating that these genes are not redundant. These results suggest that the great diversity of cell-fate decisions regulated by Notch in Drosophila may be further expanded in vertebrates by the activation of distinct Notch proteins. PMID- 1295746 TI - Increased levels of the Drosophila Abelson tyrosine kinase in nerves and muscles: subcellular localization and mutant phenotypes imply a role in cell-cell interactions. AB - Mutations in the Drosophila Abelson tyrosine kinase have pleiotropic effects late in development that lead to pupal lethality or adults with a reduced life span, reduced fecundity and rough eyes. We have examined the expression of the abl protein throughout embryonic and pupal development and analyzed mutant phenotypes in some of the tissues expressing abl. abl protein, present in all cells of the early embryo as the product of maternally contributed mRNA, transiently localizes to the region below the plasma membrane cleavage furrows as cellularization initiates. The function of this expression is not yet known. Zygotic expression of abl is first detected in the post-mitotic cells of the developing muscles and nervous system midway through embryogenesis. In later larval and pupal stages, abl protein levels are also highest in differentiating muscle and neural tissue including the photoreceptor cells of the eye. abl protein is localized subcellularly to the axons of the central nervous system, the embryonic somatic muscle attachment sites and the apical cell junctions of the imaginal disk epithelium. Evidence for abl function was obtained by analysis of mutant phenotypes in the embryonic somatic muscles and the eye imaginal disk. The expression patterns and mutant phenotypes indicate a role for abl in establishing and maintaining cell-cell interactions. PMID- 1295748 TI - Nonreceptor protein tyrosine kinases associated with neuronal development. AB - Protein tyrosine kinases (PTKs) of the nonreceptor class have been implicated in neurite outgrowth during development and regeneration of the central and peripheral nervous systems. Nonreceptor PTK encoded by mammalian proto-oncogenes (c-src, fyn, c-yes, c-abl) and their homologs in Drosophila exhibit patterns of expression and activities that suggest functions in axonal or dendritic outgrowth. These kinases may link cell surface recognition events elicited by the binding of cell adhesion molecules, extracellular matrix, or growth factors with intracellular signaling pathways in neuronal cells. The structure, localization, developmental regulation, and function of these molecules is reviewed. PMID- 1295747 TI - The fat facets gene is required for Drosophila eye and embryo development. AB - In a screen for mutations affecting Drosophila eye development, we have identified a gene called fat facets (faf) which is required for cell interactions that prevent particular cells in the developing eye from becoming photoreceptors. Analysis of eyes mosaic for faf+ and faf- cells shows that faf is required in cells near to, but outside, normal developing photoreceptors and also outside of the ectopic photoreceptors in mutant facets. faf is also essential during oogenesis, and we show that a faf-lacZ hybrid protein is localized via the first 392 amino acids of faf to the posterior pole of oocytes. Posterior localization of faf-lacZ depends on oskar. oskar encodes a key organizer of the pole plasm, a specialized cytoplasm at the posterior pole of embryos. The pole plasm is required for germ cell formation and contains the determinant of posterior polarity, encoded by nanos. Although other pole plasm components are required for localization of nanos RNA or for nanos protein function, faf is not. We have cloned the faf gene, and have shown that it encodes two similar large (approximately 300 x 10(3) M(r)) proteins that are unique with respect to other known proteins. PMID- 1295749 TI - Influence of basic fibroblast growth factor on the development of cholinoceptive neurons from fetal rat cerebrum in culture. AB - Neuronal cells from cerebral hemispheres of 14-day-old rats were grown for 6 days in a serum-free, chemically defined medium. About 95-98 and 3% of these cells were neurofilament and acetylcholinesterase (AChE)-positive, respectively. The addition of basic fibroblast growth factor (bFGF) at three developmental stages, i.e. at 4 h, 2 and 4 days resulted in an increase (about 2-fold) of the number of AChE-positive neurons. The enzyme reaction was present in the cell body as well as in the fibers, which often ramified extensively under the influence of bFGF. Treatment with bFGF after the 2nd day of culture had no or only a low stimulatory effect. Our findings indicate that bFGF affects the development of AChE containing neurons, i.e. cholinoceptive neurons from rat cerebrum. PMID- 1295750 TI - Thyroid hormone promotes transient nerve growth factor synthesis in rat cerebellar neuroblasts. AB - Primary cultures of cerebellum from 5-day-old rats indicated that proliferating neuroblasts synthesize and release nerve growth factor (NGF). Since NGF promotes DNA synthesis in these cells, our findings demonstrate that the early developing cerebellum is a suitable physiological model for studying the autocrine mitogenic action of NGF. Thyroid deficiency led to a greater reduction in the NGF content of the cerebellum than of the olfactory bulbs or hippocampus. Cerebellar NGF mRNA was also very sensitive to hormone deprivation. Physiological amounts of thyroid hormone stimulated both the mitotic activity and NGF production of cultured cerebellar neuroblasts. A lack of thyroid hormone is known to markedly alter cell formation in the cerebellum where postnatal neurogenesis is highly significant, in contrast to the olfactory bulbs and hippocampus. Taken together, these results suggest that the hormonal control of cell formation in the cerebellum is, at least partly, mediated by the autocrine mitogenic action of NGF. The thyroid hormone could temporally regulate the transient NGF synthesis by cerebellar neuroblasts directly and/or through its ontogenetic action, and hence all the NGF dependent trophic effects. PMID- 1295751 TI - Regulation of a beta-galactoside-binding lectin and potential ligands during postnatal maturation of rat brain. AB - Variations in expression and activity of a beta-galactoside-specific lectin were quantified during postnatal maturation of the rat brain. Lectin expression, estimated from enzymatic immunoassay data, and lectin activity, evaluated by rabbit erythrocyte agglutination, are higher in the brains of young animals (5 days after birth) than in older ones (2 months of postnatal life). Concurrently, modifications in glycosylation during cellular differentiation were detected by affinoblotting using a biotinylated derivative of a beta-galactoside-specific brain lectin. This study shows that membrane and cytosolic glycoconjugates of the rat brain bear appropriate beta-galactoside moieties which may be recognized by an endogenous lectin expressed in the tissue itself in relation to brain maturation. The observed variations in the expression of lectin and complementary glycoconjugates can be correlated with significant events of rat brain development. PMID- 1295752 TI - Demonstration of segmental arrangement of thoracic spinal motor neurons using lipophilic dyes. AB - Unlike the afferent input into the spinal cord, it is generally believed that the motor efferent system in the mammalian spinal cord is more segmental in arrangement. Isolated comments in recent reports suggest that motor neurons in the mammalian spinal cord may be strictly segmental, contrary to many earlier reports using less sophisticated methods. We have attempted to address the question of the segmental arrangement of motor neurons in a mammalian spinal cord using single and double labelling with the fluorescent lipophilic dyes, Di I and Di A. These dyes have the ability to diffuse along and stain the plasma membrane of the neural elements in aldehyde-fixed specimens. Sprague-Dawley rat fetuses and early postnatal pups were used. The study was conducted on the thoracic spinal cord. The results confirm that thoracic spinal motor neurons are restricted to the segments from which their axons exit via the ventral roots in the intrauterine stages of development. The segmental arrangement of motor neurons in the thoracic spinal cord corresponded well with that of the sympathetic preganglionic neurons which were stained simultaneously. PMID- 1295753 TI - Role of human microflora in health and disease. AB - The human host and its microbial flora constitute a complex ecosystem whose equilibrium serves as a remarkable example of reciprocal adaptation. Intestinal bacteria play an important role in the development of the immune system. The normal intestinal flora is responsible for resistance to colonization by exogenous pathogenic microorganisms. Nevertheless, it also constitutes a reservoir of potentially pathogenic bacteria in close contact with the host. These bacteria are responsible for opportunistic infections in immunocompromised hosts. The equilibrium of the flora can be upset by antibiotics, leading to infections as a result of proliferation of antibiotic-resistant pathogenic bacteria. PMID- 1295754 TI - Resistance of anaerobic bacteria to antimicrobial agents in Spain. AB - As a consequence of antibiotic consumption, the entire microbial ecosystem attached to man is evolving towards resistance. In Spain, penicillin resistance (MIC > 0.5 mg/l) is found in about 10% of Peptostreptococcus, Clostridium perfringens and Eubacterium, and in 50% of Veillonella. Cefoxitin resistance ( > 2 mg/l) is present in 10 to 20% of Peptostreptococcus and Clostridium, and in 50% of Eubacterium; 21% of Bacteroides (fragilis group) strains are resistant to 16 mg/l. A very low rate of imipenem resistance (> or = 128 mg/l) is found among Bacteroides (1%), but for 5% of the isolates MICs of imipenem are 2 to 4 mg/l. Metronidazole resistance ( > 8 mg/l) is found in 5 to 10% of Peptostreptococcus, Clostridium and Veillonella, and in less than 1% of the Bacteroides fragilis group. Erythromycin resistance ( > 2 mg/l) is present in over two-thirds of the Peptostreptococcus, Veillonella and Fusobacterium isolates, and in 27% of the Clostridium perfringens strains. Clindamycin resistance ( > 4 mg/l) is found in 10 to 20% of the Peptostreptococcus, Clostridium and Eubacterium isolates, and in 20% of the Bacteroides of the fragilis group, this rate being higher (30%) among faecal isolates. PMID- 1295755 TI - Clinical relevance of antimicrobial susceptibility testing. AB - In recent years, significant resistance to antimicrobial agents has been encountered among certain anaerobic bacteria. Susceptibility patterns vary from region to region, but even within a given region susceptibility is not always predictable. Initially, therapy of mixed anaerobic infections must be empirical, based on the nature of the infection, the usual flora of such infections, anticipated modification of this flora by pathophysiologic processes or prior antimicrobial therapy, and evaluation of Gram stains from appropriate specimens. If the infection does not respond well or the patient requires long-term therapy, antimicrobial susceptibility testing may be indicated in order to provide optimum therapy. Susceptibility testing is also indicated for determination of the usual patterns in a particular hospital, for monitoring geographical patterns, and to determine the activity of new antimicrobial agents. PMID- 1295757 TI - Methods for the isolation and identification of obligate anaerobes. AB - The methods used for the isolation and identification of obligate anaerobes often appear to be exactly the same as those used 20 years ago. However, careful evaluation of the methodology available reveals many improvements in technology. More importantly, the use of computerized instrumentation and new, non-growth dependent methods for characterization suggest that in the next few years even greater changes will occur in systems for identification of this group of organisms. PMID- 1295756 TI - Review of methods for susceptibility testing of anaerobes. AB - In the USA, the National Committee for Clinical Laboratory Standards has studied and published a reference agar dilution method for the susceptibility testing of anaerobic bacteria. While numerous investigators both in Europe and the USA have evaluated a variety of methods with a variety of modifications, only the broth microdilution method appears to be appropriate for routine use. The problems of the choice of breakpoint, inoculum size, media, media additives, endpoint recognition and other parameters affecting test performance and interpretation, while troublesome for anaerobes, are not unique to this group of organisms. The increasing resistance of anaerobes and the ever existing need to provide therapeutic guidance, surveillance for resistance and susceptibility data on new drugs make the need for an accurate and reliable susceptibility test for anaerobes critical. The newer methods, while showing promise, need further evaluation with all agents that have a therapeutic indication for anaerobic infections. PMID- 1295759 TI - Clinical importance of Bilophila wadsworthia. AB - Bilophila wadsworthia is an anaerobic, gram-negative, asaccharolytic, urease positive, bile-resistant, catalase-positive bacillus, originally recovered from infections in patients with gangrenous and perforated appendicitis. Additional isolations from clinical specimens, including pleural fluid, joint fluid, blood and pus from a scrotal abscess, mandibular osteomyelitis and axillary hidradenitis suppurativa are described here. Bilophila is found as normal flora in feces and, occasionally, in saliva and in the vagina. Isolates from humans are usually beta-lactamase positive and therefore resistant to certain beta-lactam antibiotics. Two percent of strains are also resistant to clindamycin. PMID- 1295758 TI - Epidemiological aspects of infections caused by Bacteroides fragilis and Clostridium difficile. AB - Bacteroides fragilis and Clostridium difficile are two of the most common anaerobes associated with human disease. Studies on the epidemiology of Bacteroides fragilis are limited and are based predominantly on serogrouping, which suggests intraspecies differences. Further studies using newer techniques for typing are required to elucidate the epidemiological characteristics of this important pathogen. By contrast, numerous phenotypic, immunological and molecular methods have been developed for typing and fingerprinting of Clostridium difficile and applied in epidemiological studies to show conclusively that Clostridium difficile is nosocomially acquired and that there is transmission and cross-infection between hospital patients. PMID- 1295760 TI - Role of fibrin deposition in the pathogenesis of intraabdominal infection. AB - The production of fibrinous exudates plays an important role in determining the outcome of peritoneal infection. Large numbers of bacteria are sequestered within fibrin matrices, thereby retarding bacterial spread throughout the peritoneal cavity and into the bloodstream. This walling-off process is teleologically advantageous in that it lessens early rapid mortality. Recent studies have documented that this same process is probably integral to the development of residual infection in the peritoneum. Bacteria sequestered within fibrin deposits are protected from normal host clearance mechanisms, thereby permitting unopposed proliferation and ultimately the establishment of an abscess. A complete understanding of the cellular and noncellular aspects of the host response to peritoneal infection will suggest novel strategies both to treat and to prevent the development of intraabdominal abscesses and their attendant consequences. PMID- 1295761 TI - In vitro susceptibility of clinical isolates of Bacteroides fragilis and Bacteroides thetaiotaomicron in Japan. AB - A nationwide survey of the susceptibility of 433 isolates of Bacteroides fragilis and 149 isolates of Bacteroides thetaiotaomicron was conducted from December 1986 through November 1989 in Japan. These strains were collected from 16 university hospitals and one metropolitan hospital. Metronidazole was the most active drug against both species, with no resistant isolates found. The activity of imipenem and sulbactam-cefoperazone was good, with very low resistance rates determined in Bacteroides fragilis (1.4% and 1.6%, respectively) and in Bacteroides thetaiotaomicron (3.4% for both drugs), and was comparable to that of metronidazole. Cefoxitin, cefmetazole, cefotetan, cefbuperazone, latamoxef and ceftizoxime were found to be more active against Bacteroides fragilis, for which resistance rates were 3.2 to 9.5%, than against Bacteroides thetaiotaomicron, for which resistance rates were 18.1 to 21.8%. Rates of piperacillin resistance in the two species were 12.9% and 26.8%, respectively. Clindamycin was very active at a low concentration (MIC50 of 0.39 to 1.56 mg/l), but 24% and 27.5% of Bacteroides fragilis and Bacteroides thetaiotaomicron isolates, respectively, were resistant to this agent. PMID- 1295762 TI - German multicentre study on the in vitro susceptibility of Bacteroides species. The German Bacteroides Study Group. AB - In 1990 the first German multicentre study on the in vitro susceptibility of Bacteroides species was completed. Employing a commercially prepared microbroth dilution assay, nine participating institutions evaluated approximately 100 consecutive isolates of Bacteroides species from relevant clinical specimens. A total of 911 strains (449 Bacteroides fragilis, 201 Bacteroides thetaiotaomicron, 79 Bacteroides ovatus, 78 Bacteroides vulgatus, 77 Bacteroides distasonis, 25 Bacteroides uniformis, 2 others) were tested. Most of the isolates came from surgical patients (72%); other sources included gynaecological patients (9%) and medical patients (5%). Seventy-eight percent of the anaerobes were found in mixed culture together with at least one aerobic organism (Escherichia coli 36%, streptococci 15%, or enterococci 13%), while in 22% of the cases, the anaerobes were the only bacteria grown from the specimens. The results showed that many of the strains were potent beta-lactamase producers (as judged by resistance to amoxicillin). However, all but one of the isolates demonstrated susceptibility in vitro when clavulanic acid was added to amoxicillin or ticarcillin. At the same time, 13% of the organisms were resistant to mezlocillin, 5% to cefoxitin and 4% to clindamycin. Three strains were reported resistant to imipenem and one strain to metronidazole. PMID- 1295763 TI - beta-Lactamase production and susceptibility of US and European anaerobic gram negative bacilli to beta-lactams and other agents. AB - The susceptibility of 1,476 US and European strains of anaerobic gram-negative bacilli to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was determined. All of the Bacteroides fragilis group and 51% of the non-Bacteroides fragilis group were beta-lactamase positive. Amongst the non-Bacteroides fragilis group, beta-lactamase positivity rates were higher for US strains (58%) than for European strains (39%). All strains were susceptible to imipenem and metronidazole. MIC90s of amoxicillin and ticarcillin for all beta-lactamase negative strains were 0.5 and 2 micrograms/ml, respectively. The addition of clavulanate reduced the MIC90s of amoxicillin (> or = 256 micrograms/ml) and ticarcillin (> or = 64 micrograms/ml) to 16 and 8 micrograms/ml, respectively, for the Bacteroides fragilis group, and to 4 micrograms/ml for both agents for the non-Bacteroides fragilis beta-lactamase producing group. Twenty-nine cefoxitin-resistant strains were found, mainly in the Bacteroides fragilis group, while 95 beta-lactamase producing strains (predominantly Bacteroides fragilis group and fusobacteria) did not show synergy between beta-lactams and clavulanate. Of the newe agents tested, meropenem and piperacillin-tazobactam were the most active (100% of strains susceptible), followed by amoxicillin-BRL 42715 (99% of strains susceptible); 94 to 98% of the strains were susceptible to cefoperazone-sulbactam, tosufloxacin, temafloxacin and clindamycin. Only 73% of the strains were susceptible to cefotetan, compared to 91% to cefoxitin; 88% of the strains were susceptible to trospectomycin. Overall, all of the beta lactam/beta-lactamase inhibitor combinations, imipenem, meropenem, cefoxitin, tosufloxacin, temafloxacin and clindamycin had good activity against beta lactamase producing strains, while all agents tested had good activity against beta-lactamase negative strains. PMID- 1295764 TI - Survey of the susceptibility patterns of Bacteroides fragilis group strains in France from 1977 to 1992. AB - Rates of antibiotic resistance within the Bacteroides fragilis group were monitored over a 15-year period in France by examining studies that employed the same methodology to test susceptibility of anaerobic bacteria. Chloramphenicol, metronidazole, beta-lactam/beta-lactamase inhibitor combinations and imipenem remained very active against Bacteroides fragilis. There was little or no change in rates of resistance to these antibiotics. Resistance to clindamycin increased from 1% in 1977 to a peak of 19% in 1987, and since then has remained at 8 to 12%. There was some evidence that resistance to most beta-lactam agents increased during the same period. These results emphasize the need for periodic surveys of resistance patterns of the Bacteroides fragilis group in each country. PMID- 1295766 TI - Comparison of the autoSCAN-W/A and Vitek Automicrobic systems for identification and susceptibility testing of bacteria. AB - The identification and susceptibility testing of bacteria by the autoSCAN-W/A rapid panels and Vitek Automicrobic systems were compared. A total of 291 clinical isolates, including 207 members of the Enterobacteriaceae, 41 nonfermentative gram-negative bacilli, 31 Staphylococcus aureus strains and 12 Enterococcus faecalis strains, were tested. autoSCAN-W/A and Vitek correctly identified 93% and 94% respectively of the Enterobacteriaceae, the identification in an additional 2% and 5% of strains respectively being reported as correct with a low probability. autoSCAN-W/A reported all identification results within 2 h after inoculation, whereas Vitek reported the identification results for the majority of gram-negative bacilli between 4 h and 6 h after inoculation. autoSCAN W/A and Vitek reported 81% and 74% of MIC results respectively after 3-6 h incubation. The rates of very major susceptibility errors were 0.4% and 0.4% for autoSCAN-W/A and Vitek respectively, the rates of major errors 0.4% and 1% respectively, and the rates of minor errors 4% and 3% respectively. Six of 30 Pseudomonas aeruginosa strains failed to grow sufficiently for susceptibility testing in the autoSCAN-W/A system, and four Xanthomonas maltophilia strains had insufficient growth for susceptibility testing in both systems. The majority of results of susceptibility testing of nonfermentative gram-negative bacilli were reported more than 6 h after inoculation. Both systems were reliable and easy to operate, and gave accurate results for common clinical isolates. PMID- 1295765 TI - Value of measurement of C-reactive protein in febrile patients with hematological malignancies. AB - The maximum serum levels of C-reactive protein (CRP) in 126 patients with hematological malignancies who had 554 febrile episodes were analyzed retrospectively with regard to documented infections and fever of unknown origin. The CRP levels were significantly higher when the blood culture was positive than when it was negative (p = 0.002). The CRP levels were significantly higher when the infection focus was identified than when it was not (p = 0.010). In patients with fever of unknown origin the CRP was significantly lower than in patients with microbiologically documented infections (p < 0.001). Cytotoxic treatment neither reduced nor enhanced the CRP reaction. The serial measurement of CRP is a reliable and readily available means for differentiating between bacterial infections and other causes of fever in patients with hematological malignancies, also during neutropenia and after cytotoxic treatment. PMID- 1295767 TI - Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus. AB - In an attempt to identify risk factors for Staphylococcus aureus septicemia, 136 consecutive HIV-infected patients were investigated for the presence of nasopharyngeal colonization with Staphylococcus aureus and subsequent Staphylococcus aureus infection. Sixty of 136 (44.1%) HIV-infected patients had staphylococci which were detected in the nasopharynx on initial culture compared to 12 of 39 (30.8%) patients with chronic diseases and 11 of 47 (23.4%) healthy hospital staff. Another 12 HIV-infected subjects proved to be Staphylococcus aureus carriers on follow-up cultures. Patients with full-blown AIDS had a higher carriage rate compared to subjects who were only HIV-positive (p < 0.05), indicating that Staphylococcus aureus colonized patients were more severely ill. Eight patients with Staphylococcus aureus septicemia were observed, all of whom were carriers; no septicemia occurred in the non-colonized patients (p < 0.01). Colonized patients with neutropenia (< 1000/microliters) were significantly more likely to develop septicemia (p < 0.01). Nasopharyngeal colonization with Staphylococcus aureus and the presence of an indwelling catheter were established to be factors that help identify patients at risk of acquiring subsequent Staphylococcus aureus infection. PMID- 1295769 TI - Anaerobic bacteria and infections. Introduction. PMID- 1295768 TI - Widespread occurrence of multiple drug-resistant Salmonella typhi in India. AB - Sixteen multiple drug resistant strains of Salmonella typhi belonging to Vi-phage types E1 (14) and O (2) and isolated in Southeast India in 1991 were characterized. All strains were resistant to chloramphenicol and the majority to trimethoprim and ampicillin. In all strains these resistances were encoded by plasmids of the H1 incompatibility group with molecular weights ranging from 110 to 120 megadaltons. Physicians in European countries should be aware that treatment may fail if patients with typhoid fever who have recently returned from the Indian sub-continent are given first-line treatment with chloramphenicol, trimethoprim or ampicillin. With the possible exception of young children, ciprofloxacin is currently the best choice for treatment of such patients. PMID- 1295771 TI - Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine. AB - The combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul treatment was examined in sublethally and lethally whole-body gamma-irradiated mice. The enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated when a single dose of Ivastimul was administered after irradiation. Ameliorative influence of combined radioprotection may be explained by the haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul. PMID- 1295770 TI - Current antimicrobial therapy of anaerobic infections. AB - The treatment of many anaerobic infections involves antimicrobial therapy, appropriate surgical drainage of abscesses, and debridement of devitalized tissue. Most anaerobic infections are polymicrobial and require treatment with agents active against an array of aerobic and anaerobic bacteria. Bacterial resistance, especially to penicillins and tetracyclines, but also to newer agents of other classes, continues to increase. As a result, treatment with more than one drug is often required. Combination therapy is often necessary in serious infection, and is indicated for empiric treatment before receiving culture results. In the past combination therapy has been the mainstay of antimicrobial therapy, but more recent studies suggest that monotherapy for anaerobic infections may dominate the future. Selection of an agent requires consideration of the site of infection and the most likely etiologic agents. In vitro susceptibility is important, but it is not the only determinant of antimicrobial effectiveness. The pharmacology of the drug--absorption, distribution, concentrations in body fluids and tissues, excretion and metabolism--also plays an important role. The nature and severity of the underlying illness are important factors in selecting empiric therapy. Although it is a clinical judgement, in patients considered to have mild to moderate infections, several factors in selecting antimicrobial agents may be considered, including cost, whereas in patients judged to have severe or life-threatening infections, the most potent agents should be chosen as initial therapy, regardless of cost. Finally, the toxicities of the agent must also be considered. PMID- 1295772 TI - Distribution of triiodothyronine nuclear receptors during the cell cycle in mouse leukemia cells. AB - The process of the appearance of thyroid hormone receptors in the cell cycle was studied in mouse leukemia cells L1210. After cell synchronization by 2 mM thymidine for 12 h followed by 80 nM Colcemid for 4 h, the specific binding of triiodothyronine (T3) to its nuclear receptors was determined 3, 6, 9 and 12 h after release from the thymidine-Colcemid block. Three h after release from the block, [125I]T3 specific binding was 11.4 +/- 2.5% of a control value measured for an asynchronous population. An upward slope in progression of T3 nuclear receptors was found 6 h (32.3% +/- 4.5%), 9 h (47.8% +/- 5.2%) and 12 h (83% +/- 4.3%) after release from thymidine-Colcemid block. The data suggest that processes involving T3 receptor promotion in cell nuclei are operative within the late G1 and S phases of the cell cycle, and thus the increase in T3 receptor concentration in the nuclei is in a positive correlation with the number of cells in the S compartment of the cell cycle. PMID- 1295773 TI - Defective function of blood granulocytes in patients with diabetes mellitus associated marginal periodontitis. AB - In ten periodontitis patients suffering from type I diabetes mellitus, phagocytic activity, aggregation and chemiluminescence generation of blood granulocytes were determined. Compared to controls with clinically healthy periodontal conditions, the phagocytosis of zymosan particles and the aggregation response induced by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine were significantly decreased, whereas aggregation induced by the platelet-activating factor, a potent mediator of inflammation, was significantly enhanced. PMID- 1295774 TI - [Enzyme deficiency of erythrocytes in human porphyria]. AB - Hereditary enzyme deficiency in porphyrias can be recognized in blood cells. In the red cell four enzymes of heme biosynthesis can be detected: porphobilinogen synthase (delta-aminolevulinic acid dehydrase), uroporphyrinogen synthase, cosynthase, and decarboxylase. A decrease of porphobilinogen synthase is observed in lead intoxication and in a new type of hereditary acute porphyria with nearly total enzyme deficiency in the homozygous state with a residual activity of 1-2% of controls. In another recessive condition, congenital erythropoietic porphyria, the deficient uroporphyrinogen cosynthase shows an activity between 1 and 20%. Acute intermittent porphyria is characterized by diminished uroporphyrinogen synthase which allows the recognition of gene carriers in red cells. In the genetic type of porphyria cutanea tarda triggered by alcohol, oral contraceptives, and liver damage the uroporphyrinogen decarboxylase is decreased to about 50%. In hepatoerythropoietic porphyria, a homozygous variant of porphyria cutanea tarda, decarboxylase activity was found below 10% of controls. With exception of congenital erythropoietic, hepatoerythropoietic porphyria, and lead poisoning enzyme deficiencies of porphyrin metabolism in red cells do not lead to anemia. PMID- 1295775 TI - [Effectiveness of comprehensive treatment with Normosang and plasmapheresis in acute intermittent porphyria]. PMID- 1295776 TI - [Erythrocyte membrane lipid composition in patient with iron deficiency anemia during treatment]. AB - Red blood cell membrane lipid composition was studied in 51 iron deficiency anemia patients, in 10 of them during ferro-therapy. It was noted that red blood cell membranes contained increased total levels of lipids, phospholipids and significantly decreased levels of cholesterol esters and lysophospholipids. During the treatment, in the presence of a distinct process of the recovery of disturbed lipid composition of red blood cell membranes, a significant increase was recorded in the content of triglycerides, phosphatidyl amines, while phosphatidyl and cardiolipin levels were significantly lowered. Red blood cell membrane lipid content in iron deficiency anemia patients and its dynamics in the process of their treatment might serve as an additional criteria of the body saturation with iron. PMID- 1295777 TI - [Erythrocyte membrane proteins in patients with hereditary spherocytosis]. AB - Red blood cell membrane proteins were studied in a group of patients with hereditary spherocytosis, in comparison with normal donors, to reveal anomalous proteins associated with this disease. For this purpose red blood cells of the patients and normal donors were fractionated, by the age, in Ficoll-400 gradient, as a result red blood cell membranes were obtained with proteins that were investigated by the method of two-dimensional electrophoresis. In comparison of two-dimensional electrophoregrams of red blood cell membrane proteins of normal donors and those of microspherocytosis patients it was found that the latters had additional peptides in the area of glyceraldehyde-3-phosphate hydrogenase and pyruvate kinase. The changes detected in the red blood cell membrane protein composition might be caused by age shifts in the red blood cell population or by the disease type. PMID- 1295778 TI - [Comprehensive evaluation of hemostasis in essential athrombia and Glanzmann thrombasthenia]. PMID- 1295779 TI - [Changes in aggregation and physico-chemical properties of blood in vibration disease]. PMID- 1295780 TI - [Organization and results of studies on acute hepatic porphyrias in Poland]. AB - The organization, activities and experience of Porphyria Reference Centre of the Institute of Hematology in Poland is shown. A total of 214 families with acute hepatic porphyria were collected. The family studies in search of latent cases were conducted, and measures for preventing the disease attacks were taken. The therapy of the attacks consisted in glucose and heme arginate infusions, and hyperalimentation in the patients is stressed. The incidence rate of porphyrias in Poland, according to the material collected at the Institute of Hematology is 1:15,000 inhabitants, however, it is suggested that the true value is much higher. PMID- 1295781 TI - [Current ideas for the correction of hemostatic disorders in patients with hemorrhagic vasculitis]. PMID- 1295782 TI - [Diagnosis and treatment of acute porphyria]. PMID- 1295783 TI - [Antibiotics as regulators of immunity]. PMID- 1295784 TI - [Lipid composition of erythrocyte stroma in patients with iron-deficiency anemia and its treatment-induced dynamics]. PMID- 1295785 TI - [Determination of the activity of the pathologic process in hypoplastic (aplastic) anemia]. PMID- 1295786 TI - [Importance of "minor" erythrocytic antigens in selecting donors giving blood for transfusion to patients]. PMID- 1295787 TI - [The results and prospects of research on the hygiene of the industrial microclimate]. AB - The main directions in the research and study of industrial microclimate are represented in the article. Evaluation of the microclimate based on thermophysiology, studies of correlation between the environmental temperature and the human functional status helped to establish the normal parameters, measures of the overheating and the overcooling prophylaxis. New data about the immediate and late effect of single microclimate parameters on the human functional status necessitate the creation of new methodic approaches to the evaluation and control of microclimate conditions. PMID- 1295788 TI - [The prevention of vibration disease]. AB - Probable cooling of hands must be taken into account in setting up the prophylaxis of pathology due to the local vibration. Warm air pumped into the manual pneumatic devices can eliminate the cooling of operators' hands. The same effect is gained by the physiotherapeutic procedure--the warming and micromassage of hands by the dry air. PMID- 1295789 TI - [The effect of hyperbaric oxygenation on the tissue oxygen balance and hemodynamics in miners with vibration-induced pathology]. PMID- 1295790 TI - [The hygienic assessment of the working conditions and health status of workers on the petroleum tank farms of Bashkiria]. AB - Work conditions and the health status in workers of Bashkirian oil enterprises are characterized. Exposure to oil products composed of alkanes and aromatics, petrol and tetraethyl lead was proved to be the major hazard for workers of all the occupations. Complex of occupational and industrial hazards of Bashkirian oil enterprises harms the health status of workers, which induces the high prevalence of chronic diseases. PMID- 1295791 TI - [The function of 2 detoxifying body systems in workers of the petrochemical industry]. AB - Studies of the immune status and antipyrine test helped to analyse the status of the two body detoxicants--the immune system and the system of microsomal hepatic oxygenases in petrochemical production workers suffering from the chronic bronchitis and bronchial asthma. Immune deficiency of T and B cells, decreased function of cytochrome P-450 containing monooxygenase system were revealed, which indicates complicated relations between the two body detoxicant systems. PMID- 1295792 TI - [Human functional status in combined exposure to industrial factors and mining migrations]. AB - The functional status and capacity for work were studied in humans exposed to the combined occupational and natural (everyday mountainous migrations) factors. Occupational factors and vertical migration appeared to effect synergistically on functional systems, which necessitates the further investigations concerning the work normalization in mountainous conditions. PMID- 1295793 TI - [The basic dynamic indices and structure of morbidity with temporary loss of work capacity in workers of the reactor industry]. AB - Retrospective analysis of morbidity with the transitory disablement in male workers of industrial nuclear reactors during the recent 5 years revealed moderate and low levels of morbidity in causes and days for 100 workers. Respiratory tract diseases, mainly acute, take the first place in the morbidity structure. Parameters were not found depending on age, length of service, total gamma-radiation dose. PMID- 1295794 TI - [Cellular immunity indices in combined chronic exposure to stress and low concentrations of carbon monoxide (II). Experimental research]. AB - Studies of the chronic combined effects of carbon monoxide low concentrations and psychoemotional stress revealed changes in the peripheral lymphocyte subpopulation in all groups of examinees, connected with the defense activation of the humoral immunity and functional decrease of T lymphocytes. Analysis of correlations of cell subpopulations revealed disorders of their relationships, augmenting with the intensity of exposure. Combined action of carbon monoxide in the maximal of studies concentrations with stress resulted in the most severe changes of nonspecific immunity, which proves decompensated decrease of immunity. PMID- 1295796 TI - [The industrial hygiene of auxiliary workers (a review of the literature)]. PMID- 1295795 TI - [The epidemiological assessment of the "dose-response" relationship in the hygienic regulation of asbestos-containing dusts]. AB - "Dose-response" dependence worked out by American scientists helped to reveal the linear dependence between carcinogenic risk factor, asbestos containing dust, and lung cancer formation, use it for basing the new MAC for asbestos containing dust taking into account the oncologic security. PMID- 1295797 TI - [Thermoregulatory characteristics in exposure to high temperature combined with low air humidity]. AB - Sweat evaporation from the skin surface and wearing the loose cotton shirt are proved to diminish the exposure to the high environmental temperature and prevent overheating. Recommendation for prevention of the overheating are suggested. PMID- 1295798 TI - [The article by G. Ia. Lipatov The dust factor, its action on the body and the prevention of worker morbidity in the smelting of copper and nickel ores (Gigiena truda i profzabolevaniia, 1990, No. 9, pp. 34-7)]. PMID- 1295799 TI - [The methodological characteristics of calculating the prevented economic loss from disability resulting from occupational diseases in assessing the activities of occupational pathology centers]. AB - Evaluation of prevented economic detriment from the occupational disablement can be used for estimating the economic efficiency of occupational centre activities. Decreased disability pensions as a main item of expenses must be taken into account in evaluation of prevented economic detriment due to the diminished disablement. Regional occupational pathology centre activities aimed at the early diagnosis of complications-free occupational diseases, complete clinical screening, active treatment and control of the adequate employment give a great social and economic effect. PMID- 1295800 TI - [The physicochemical characteristics of the dust formed during wood working and furniture manufacture and its effect on the development of pathological processes in the upper respiratory tract]. PMID- 1295801 TI - [The activities of the International Programme on Chemical Safety--IPCS]. PMID- 1295802 TI - [A method for recording the deep temperature of the human body under cooling and warming microclimatic conditions]. AB - The simple and safe method for the deep body temperature measurement is worked out. The temperature is measured by means of the heat point-sensor and fully corresponds to the deep body temperature. The maximal temperature of the voided urine was measured. The rectal temperature completely coincides with the measured by the stated method in healthy men exposed to high, low and contrast temperatures of air and water. PMID- 1295803 TI - [The development of occupational hearing loss under the influence of pulsed noise]. AB - The deafness was studied in workers engaged into the weaving and the blacksmithing. Both groups of workers were exposed to the noise dose of 109 dB estimated according to Robinson's formula. Processing of received data in diminished hearing revealed the reliable difference between the studies groups both in quantity of the cochlear neuritis and the grade of the hearing failure. Slight hearing failure predominated in the weavers' group whereas the moderate and severe forms appeared in the blacksmiths. Analysis revealed the positive correlation between the overall noise dose and diminished hearing in all studied groups concerning high and voice frequencies. The impulsive noise appeared to be more aggressive than the constant one. PMID- 1295804 TI - [Neuroorthopedics--a "concerted action". Interdisciplinary therapeutic concepts are required. Report from the Neuroorthopedic Symposium 1992 in Bayreuth, 23 May 1992]. PMID- 1295805 TI - [Differential pain therapy for backache. Guidelines for classification and therapy for backache. Reported from the Committee of the German Society for the Study of Pain and the German Society of Rheumatology Consensus Conference: Dresden, February 1992]. PMID- 1295807 TI - Growth as a measure of the nutritional and hygienic status of a population. AB - The history of the use of children's growth as a measure of the nutrition and hygiene of a population since the early 19th century is outlined. Secular trends towards greater height and earlier maturity are reported; the increase in adult height in British men born between 1900 and 1946 averaged about 1.25 cm/decade and in those born between 1946 and 1960 0.6 cm/decade, according to the data of Kuh et al. [Int J Epidemiol 1991;20:1001-1009]. Social class differences in height persist in the UK, amounting to almost 2 cm between the well off and the unskilled. The average height of subgroups of most populations serves well as a proxy for their health status and relates to their mortality rate. PMID- 1295806 TI - Interrelations between growth hormone and sex hormones: physiology and therapeutic consequences. AB - Animal experiments, analysis of growth hormone (GH) secretion in the human, studies on the synergistic metabolic effects between GH and sex hormones using the stable isotope 15N, and long-term growth evaluation of patients with GH and gonadotrophin deficiency treated with testosterone and hGH show that biologically important interrelations exist between GH and sex hormones. They are operative not only at the pituitary and gonadal levels but also in peripheral tissues, where sex hormones modify the metabolic and growth-promoting effects of GH. GH is also important for an optimal androgenic effect of testosterone in development of secondary sexual characteristics. Knowledge of these interrelations is not only of physiological interest, but also of practical clinical value. PMID- 1295808 TI - Growth hormone and ovulation: is there an indication for treatment of infertile women with growth hormone? AB - We have explored the use of growth hormone (GH) for ovulation induction and ovarian stimulation for in vitro fertilization and embryo transfer (IVF-ET). We first compared the effects of co-treatment with GH and placebo on the dose of gonadotrophins required to induce ovulation. The patients were gonadotrophin deficient and, for the main part, hypopituitary. We found a significant reduction in the dose of gonadotrophins and the duration of treatment needed to induce ovulation. The dose of GH used in these studies was substantial, and we await the results of a multi-centre trial attempting to establish a dose-response relationship. We then explored the role of GH in patients undergoing IVF-ET. The end-point measured was an increase in the number of follicles developing during standard treatment with gonadotrophins. In the first randomized controlled clinical trial we found a suggestion only of an enhanced ovarian response to co treatment with GH. Specifically selected patients with ultrasound-diagnosed polycystic ovaries were then treated. All were receiving treatment with luteinizing hormone-releasing hormone analogue as part of their ovarian stimulation protocol. The results showed clearly that in this group of patients, co-treatment with GH augmented the ovarian response to treatment with gonadotrophins. We also found an increase in serum and follicular-fluid insulin like growth factor I (IGF-I) concentrations, but since the serum concentrations always exceeded those in follicular fluid, the results were consistent with the notion that follicular-fluid growth factor was predominantly derived from serum IGF-I rather than being synthesized locally. PMID- 1295809 TI - The role of growth hormone and insulin-like growth factor I in the regulation of male reproductive function. AB - Animal experiments and clinical studies on the interactions between growth hormone (GH) and the male hypothalamic-pituitary-gonadal axis have predominantly concentrated on GH and sex steroid interactions in the regulation of growth and development, or on the metabolic effects of GH. In contrast, little attention has been paid to the possible effects of GH on spermatogenesis, although the first report dealing with this topic was published almost 30 years ago. The interactions of GH and its main mediator, insulin-like growth factor I (IGF-I), with the hypothalamic-pituitary-gonadal axis, and their role in spermatogenesis have recently been investigated using in vitro systems and different animal models (mice and rats). Using Leydig and Sertoli cell cultures, complex interactions between GH/IGF-I and the gonadotropins affecting differentiated cell functions, e.g. steroidogenesis and cell division, have been demonstrated at the cellular level. In vivo studies using immature and mature hypophysectomized rats and GH-deficient mutant male mice and rats indicate that IGF-I can play an important role in the regulation of steroidogenesis and spermatogenesis. Furthermore, although follicle-stimulating hormone and luteinizing hormone are the major regulators of testicular IGF-I production, GH may play an indirect role by potentiating the actions of the gonadotropins in regulating testicular IGF-I content. A large proportion of men presenting at male-infertility clinics are diagnosed as having idiopathic infertility. Further studies are necessary to investigate whether defects associated with GH and/or IGF-I effects in the testis are the cause of male infertility in a small group of these patients. PMID- 1295810 TI - What is the role of growth hormone and related peptides in implantation and the development of the embryo and fetus. AB - The role of growth hormone (GH) and the related placental lactogens in implantation and subsequent embryonic and fetal development is an enigma. Firstly, these peptides are abundant in both the fetal and maternal circulation. The variant growth hormone (hGH-V) is expressed by the placental syncytiotrophoblast and is released into the maternal circulation. It is not detectable in fetal blood. Fetal pituitary (GH) is abundant but is not a primary stimulus to human fetal musculoskeletal growth, since hypopituitary newborn infants have near-normal birth size. However, pituitary hGH has been shown to stimulate pancreatic islet growth and insulin release in vitro, and to be a mitogen for fetal hepatocytes obtained in late first trimester. This selectivity of action is confirmed by the immunohistochemical localization of hGH receptor in the human fetal kidney, endocrine pancreas, liver, skin and brain during the first and second trimester, and their absence from the musculoskeletal system, gut and lung. High-affinity human placental lactogen (hPL) receptors are abundant in animal and human fetal tissues, and hPL can attain concentrations of 10 nM in the human fetal circulation. In vitro data strongly suggest anabolic and mitogenic actions for PL on fetal tissues, including amino acid transport, hepatic glycogenesis, protein synthesis, and stimulation of insulin-like growth factor and insulin release. The PL axis in the fetus is influenced by maternal nutrition. Despite these findings, definitive evidence is still lacking that PL contributes to fetal growth and development in utero. PMID- 1295811 TI - Epidemiologic survey of patients treated with growth hormone in France in the period 1959-1990: preliminary results. AB - Because the delivery of growth hormone (GH) was centralized from 1977 in France, it has been possible to conduct, during the second half of 1990, a nationwide survey of the health status of patients treated with GH from the year 1959. A questionnaire regarding the 5,546 patients recorded for the period 1959-1990 was sent to the prescribers or the patients. 5,418 more or less completely documented reports were obtained. The mean age of the patients at the onset of GH treatment was 11.0 +/- 4.1 years. 1,937 of them had at this time some important disease associated with GH deficiency. The mean duration of treatment was 3.99 +/- 3.05 years. 3,446 patients were still under follow-up. Very recent information (1990 1991) was given for 82.7% of patients, less recent data (1985-1989) for 13.4%. For 3.9%, no data beyond 1985 were obtained. 77 patients had died, 38 from neoplastic disease (mainly recurrence of a primary malignancy), 10 from accident, 3 by suicide, 7 with neurological disease [only 1 case of Creutzfeldt-Jakob disease (CJD) was reported at the time of the survey], the others from various causes. No abnormal frequency of posttreatment leukemia, lymphoma, malignancies, hip diseases, glucose intolerance or other disease focusing attention, was found in the survey. From the time when this survey was completed (December 1990) to that of this report (May 1992), other cases of CJD have been reported in France: 3 ascertained, 7 clinically resembling but not yet certain. These 10 patients were treated for complete GH deficiency, 6 of congenital or neonatal cause and 4 after neurosurgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295812 TI - Untoward events in patients treated with growth hormone in the USA. AB - Since 1960 more than 30,000 children have been treated with growth hormone (GH) in the USA. Ten cases of Creutzfeldt-Jakob disease have been associated with the use of GH purified from pituitaries in the USA, and more cases may appear in the future. Ten cases of leukemia or preleukemia have been reported in patients undergoing GH treatment in the US. Eight of these patients had previously diagnosed tumors of the central nervous system. As the indications for GH treatment broaden, and the dosages of GH increase, more unfavorable clinical events linked directly to the biological actions of GH can be expected to occur. Continued surveillance for clinically important GH-associated events is important. PMID- 1295813 TI - Tumour occurrence and recurrence. AB - There is growing concern about the oncogenic potential of growth hormone (GH) used therapeutically. In rat experiments, a variety of malignant tumours have been induced following administration of supraphysiological doses of GH, whilst in other studies in hypophysectomized animals a lower than normal incidence of carcinogen-induced neoplasms was reported. In acromegaly, in which there is a pathologically sustained high GH level, there is a significantly increased incidence of cancer in general and specifically of colonic neoplasia. To determine whether the use of GH in the treatment of radiation-induced GH deficiency causes tumour recurrence, a comparison was made of tumour recurrence rates between 47 children treated with GH for radiation-induced GH deficiency after treatment for a brain tumour and a control population from the North West Children's Cancer Registry who did not receive GH (n = 160). All cases of acute lymphoblastic leukaemia (ALL), including those that were (n = 15) and were not (n = 146) treated with GH were reviewed. The computerized tomography (CT) scans in the children with brain tumours were reviewed at the time of GH commencement and subsequently. There were 5 brain tumour recurrences after GH therapy: 1 astrocytoma, 2 ependymomas and 2 medulloblastomas. Adjusting for variables other than GH which might affect tumour recurrence, the estimated relative risk of tumour recurrence was 0.82 (95% confidence interval: 0.28-2.37). In each tumour category there was no association between the use of GH and subsequent tumour recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295814 TI - Leukemia in growth-hormone-treated patients: an update, 1992. AB - Since 1988 the number of growth hormone (GH)-treated patients has markedly increased worldwide. To date, leukemia has been observed in 31 patients during or following GH therapy and related malignancies in 2 further patients. Leukemia occurred in 10 patients in Japan, 10 in the USA, and 10 in Europe, and in 1 patient in Canada. In 29 patients GH therapy had been started in 1975 or later. The onset of leukemia was 1984 or later in 28 patients with a mean time between the start of GH therapy and leukemia onset of 5.0 (0.2-18.8) years. Patients had received both pituitary and recombinant GH in moderate doses. In 15 patients definite additional leukemia risk was evident: Fanconi anemia in 2, myelodysplastic syndrome in 1, Bloom's syndrome in 1, radiation for brain tumor (+chemotherapy) in 9, chemotherapy in 2. The leukemic patients without a strong additional risk do not represent a definitely higher leukemia incidence worldwide, except for Japan where the occurrence is higher than expected. PMID- 1295815 TI - Thyroid function during growth hormone therapy. AB - Administration of growth hormone (GH) in GH-deficient patients has been reported to cause a variety of perturbations in thyroid function. Reports range from decreased sensitivity of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation and induction of hypothyroidism to increased energy expenditure and enhanced peripheral thyroxine (T4) to triiodothyronine (T3) conversion. Some of the diversities may relate to the fact that earlier studies were uncontrolled case reports, which furthermore employed pituitary GH preparations, which may have been contaminated with TSH. A confounding variable in terms of incipient TSH insufficiency in some patients may also have been present. Data from a placebo controlled crossover study of 4-months GH therapy in GH-deficient adults, some of whom were on ongoing T4 substitution, revealed that the most prominent effect on thyroid function was increased peripheral T4 to T3 conversion without significantly affecting TSH levels or secretion from the thyroid gland. It was furthermore observed that T3 levels during placebo were significantly decreased compared to an untreated healthy control group. Comparable findings have been made in a controlled study of 6-months GH therapy in adult-onset GH-deficient patients. More recent data suggest that these effects prevail after long-term (16 months) therapy. Similar findings have also been reported in healthy subjects receiving pharmacological GH doses. It is likely that this effect is not caused by GH per se inasmuch as reduced T4 to T3 conversion is a common observation in catabolic states with concomitant GH hypersecretion. It remains to be shown whether insulin-like growth factor I (IGF-I) stimulates peripheral deiodination. PMID- 1295816 TI - Metabolic changes and vascular risk factors in hypopituitarism. AB - Adults with hypopituitarism die prematurely, and the excess mortality is from vascular disease. On echocardiography we have demonstrated abnormalities of myocardial diastolic function in hypopituitary adults, indicating possible early ischaemic change. Peripheral arterial disease is evident on ultrasonography. Vascular risk factors have also been examined. Impaired glucose tolerance and unrecognized diabetes are common in hypopituitary adults. Total cholesterol levels are elevated, particularly in hypopituitary women. The role of growth hormone (GH) deficiency in the vascular disease and in the vascular-risk-factor abnormalities is unknown at present. Prolonged GH therapy causes a decrease in the levels of fasting total cholesterol, without any adverse effects on glucose homeostasis. GH therapy trials in adults will clarify the role of GH in the excess vascular risk of hypopituitarism. Prolonged GH therapy will be necessary for the vascular effects to be defined. PMID- 1295817 TI - Human growth hormone but not insulin-like growth factor I positively affects whole-body estimates of protein metabolism. AB - Human growth hormone (rhGH) increases estimates of whole-body protein synthesis, but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In addition, rhGH stimulates protein synthesis in skeletal muscle tissue. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. Using high-dose prednisone as a controlled model for protein catabolism in normal volunteers, high-dose rhGH together with prednisone prevents the protein catabolic effects of prednisone alone. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole body proteolysis, suggestive of a predominant insulin-like effect. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. Thus, the mechanism of action of rhGH on body protein metabolism remains to be elucidated. However, rhGH alone or in combination with rhIGF-I may provide a new management strategy in a variety of protein catabolic conditions in humans. PMID- 1295818 TI - Malnutrition in Crohn's disease: substrate deficiency or misuse? AB - Growth failure is frequently associated with Crohn's disease. However, it does not seem to be fully accounted for by overt endocrinological abnormalities or nutrient deficiencies. It may be related to an abnormal utilization of available substrates, particularly proteins, due to an imbalance in protein metabolism kinetics. Its primary mechanism may be an increase in protein breakdown rates over synthesis, specifically related to the associated inflammatory syndrome, and progressively leading to a protein debt. Reduction in food intake would only exaggerate this trend by further reducing the synthesis to breakdown ratio, whereas nutrient supplementation merely compensates for the deficit by promoting protein synthesis. PMID- 1295819 TI - Growth hormone and nutrition. AB - The regulation of growth hormone (GH) secretion in humans is a complex process which comprises more than stimulation by GH-releasing hormone and suppression by somatostatin. Although these two hypothalamic hormones are the primary regulators of GH secretion, they most likely function as the final pathway through which numerous factors influence GH synthesis and secretion. Some of the modulators of GH secretion include neurotransmitters, circulating glucose, insulin-like growth factor I and gonadal steroid concentrations. Age, nutrition and body composition are also related to the amount and pattern of GH secretion in humans. The influence of nutritional status on GH secretion is becoming more clearly defined. PMID- 1295820 TI - Nutrition and the secular trend of growth. AB - Japan has been experiencing ever more rapid socioeconomic development and changes in eating habit, especially in children, since the end of the Second World War. These occurrences (westernized life style) have greatly affected the growth of Japanese. Nutrition is the most important factor in promoting the physical growth in childhood during food supply shortage, and for a relatively short term the secular trend in linear growth will reach a plateau if the food supply is adequate, but the secular trend is also limited. Since the condition for this limitation should be comprised by genetic factors, we are most interested in investigating and analyzing these genetic factors in the near future. Overeating adversely affects growth in childhood, with most common representatives of these ill effects being atherogenic risk factors such as obesity, hypertension and hypercholesterolaemia. PMID- 1295821 TI - The effects of growth hormone therapy on spontaneous sexual development. AB - We have carried out a prospective randomised study in 52 (46 male, 6 female) children with isolated growth hormone (GH) deficiency treated with a GH regimen of 15 IU/m2/week administered as a daily subcutaneous injection. At the onset of the pubertal growth spurt, the patients were randomised to receive either an unaltered regimen (26 males, 1 female) or 30 IU/m2/week (20 males, 5 females). There was no change in the frequency of GH administration. The number of females in this study was too small to give a meaningful result. In contrast, the boys treated with either dose regimen showed no significant alteration in growth rate, but there was a faster than normal progression in pubertal maturation. It is concluded that the optimum final height of children with isolated GH deficiency may not be achieved in patients without the therapeutic manipulation of the onset and/or duration of puberty. 16 short normal children (9 males, 7 females) were treated with GH in a regimen of 25 IU/m2/week (range: 20-30) as a daily subcutaneous injection. The mean age for the onset of GH treatment was 11.5 and 11.0 years in the boys and girls, respectively. Our data suggest that both boys and girls had a more rapid rate of pubertal maturation than normal. It may be that in terms of final height prognosis, the events of puberty related to GH treatment counterbalance the improvement in growth prognosis during prepuberty. PMID- 1295823 TI - "Mr. K". PMID- 1295822 TI - Effects of changes in nutritional conditions on timing of puberty: clinical evidence from adopted children and experimental studies in the male rat. AB - Among 32 patients with idiopathic central precocious puberty seen during a 3-year period, 1/4 were adopted children from developing countries who showed early sexual maturation during the catch-up process following their arrival in Belgium. To study the possible mechanism accounting for such clinical observations, we used the male rat as a model, and evaluated the effect of variations in early nutritional conditions, by manipulating litter size, on hypothalamic and testicular maturation. We had shown previously that, in the male rat, onset of puberty was preceded, between 15 and 25 days of age, by a transiently increased activation of N-methyl-D-aspartate receptors involved in a facilitatory control of pulsatile secretion of gonadotropin-releasing hormone. We also showed that the proportion of elongated spermatids in testicular cell homogenates increased between 25 and 45 days of age. When compared to pups of a small litter (6/dam), those of a large litter (14/dam) showed a reduced growth rate (1.9 vs. 3.5 g/day) before weaning (21 days), whereas they grew at a similar rate (5.6 vs. 4.7 g/day) after weaning. At 35 days of age, the animals raised in the large litter showed evidence of delayed hypothalamic and testicular maturation when compared to animals from the small litter. Reduction of litter size at 17 days allowed food restricted pups of a large litter to resume a normal growth rate before weaning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1295824 TI - ANA issues American Nurses Association position statement on HIV infection and nursing students. PMID- 1295825 TI - Florence J. Middleton. Interview by Amanda Niskar. PMID- 1295826 TI - New graduates ... the reality of the job market. PMID- 1295827 TI - Perioperative nursing: a special nursing specialty. AB - The intraoperative phase of perioperative nursing practice is a special specialty, as it combines the nursing model and the collaborative model for specialization. As a nursing model, it focuses on the behavioral sciences, education, and nursing as a caring science. As a collaborative model, it requires skilled care with an additional knowledge base acquired from medicine and the behavioral and biological sciences. The nature of the operating room may distort the image, because although nurses work closely with other health care team members in diagnosing and treating patients, in this special specialty the scope of practice is uniquely nursing. PMID- 1295828 TI - Health care platforms. PMID- 1295829 TI - Nursing images and the profession. PMID- 1295830 TI - Overview: homelessness in America. PMID- 1295831 TI - Homelessness in the south--excerpts from student journals. PMID- 1295832 TI - Nursing the homeless--problems and solutions. PMID- 1295833 TI - The silent scream of HIV. PMID- 1295834 TI - Homelessness in the midwest. PMID- 1295836 TI - A student from Hong Kong looks at American health care costs. PMID- 1295835 TI - "The nurse I admire most". PMID- 1295837 TI - Conquering stage fright. PMID- 1295838 TI - [Local corporations in the National Health System]. PMID- 1295839 TI - [Social inequalities in health in the city of Malaga]. AB - Social inequalities and health inequalities are closely related, and their reduction is the goal of international organizations and governments as well. In order to better understand the territorial distribution of social inequalities in the city of Malaga (Spain) and compare them with measured health differences, a descriptive study was done using different sources of information. Using the city's neighbourhoods as the unit of analysis, a cluster analysis was carried out based on a set of demographic, socioeconomic and standard of living indicators. This led to the configuration of six social areas within the city. In these areas, as defined by socially homogeneous criteria, diverse health indicators have been measured, leading the verification of important health differences among them. For example, clear differences in mortality rates between Area IV (socioeconomically deprived) and Area III (with a higher standard of living) are observed: the ratio between their respective "years of potential life lost" was 1.79, and between standardized mortality rates, 1.42. A similar disadvantage in low birth weight was confirmed notably so in adolescent pregnancies (five times higher). In conclusion, those areas of the city with a lower socio-economic status also had the lowest health levels. PMID- 1295840 TI - [The association between iron deficiency and learning disorders in preschoolers]. AB - With the aim preventing future problems of underachievement at school, we studied the possible relationship between learning difficulties and iron deficiency in nursery-school children. To do this, we determined the prevalence of iron deficiency and the prevalence or learning difficulties in the different areas of mental development in a sample of 136 nursery school children coming from the Alaquas public school (Valencia), aged between four and five years. Their nutritional state and ferric state, socioeconomic and cultural level, and psychomotor development were evaluated. All the children were in a good nutritional state, coming from homogeneous families as regards their socio cultural level and being divided into two groups as regards their economic situation. The iron deficiency prevalence was 17.6% in stage I (ferritina serica < 12 ng/l) and 22.8% in stage III (anemia ferropenica). The coefficient for overall development was 85.95, the lowest marks being in the speech area. A positive association (prevalence ratio = 2; IC 95% = 1.1-8.3) between iron deficiency in its III stage and changes in the specific area of analysis and synthesis. PMID- 1295841 TI - [The demand for care and systems of access in primary health care]. AB - The aim of the investigation was to assess variations in the demand for medical care in the primary care centre of Ciudad Badia (Barcelona, Spain). The records of attendance were analysed over a period of seven years. During this period, some changes were made which affected the way the centre was used by patients, such as the creation of systems which required notice of medical and nursing appointments, the reduction of spontaneous attendance, and the introduction of a card for medication for the chronically sick. These changes were accompanied initially by a decrease, then a stabilisation, and afterwards a slight increase in total number of visits. All visits (with notice) rose from 5.3% in 1983 to 45.2% in 1989. Similarly, nursing visits (with notice) increased from 4% to 9.5 of total activity. Emergency visits in the same period rose from 3.4% to 8%. It is concluded that changes that were introduced raised the level of commitment of the staff to medical work-both preventive and therapeutic, as well as the improvement of the organisation of attendance at the centre and a higher satisfaction of users of the centre and the medical staff. PMID- 1295842 TI - [The reasons for consultation and active problems. A key for the understanding of information in primary care]. AB - The aim of this work is to assess the major differences found in the information content of the registers in primary care according to whether the registration includes the Reason (s) For Encounter (as ascertained by the professional) or the Active Health Problem (s). The information used is based on an observational study of a representative sample of the consultations to eight general practitioners from the Principate of Andorra. The study was performed during the period of May-June 1989. 547 consultations are analysed. A better specificity and information content is observed when both approaches are registered. Active Health Problems seem to be barely related to Reasons for Encounter and it seems that they could have as much, if no more. Influence in the process of care, than the RFEs it selves. PMID- 1295843 TI - [Advertising, advertising legislation and health]. AB - The media and specifically magazines and sunday supplements contain advertisements, some of which can be dangerous to one's health. We have investigated these types of advertisements, which were included in the 15 top sales magazines in Spain. The period of analysis corresponded to the period april may, 1991. We have compared the results obtained with the results of a previous investigation carried our in 1987, using an identical method. We have tried to test if the so-called Law of Publicity of 1988 has had any effect on publicity. We have found, 1383 advertisements that could have a damaging effect on one's health. Although the total number of advertisements have decreased over this four year period, the law has hardly produced any influence on publicity, and we have found breaking of the law in the investigated material. PMID- 1295844 TI - [The possibilities for the participation of local corporations in the management of health services]. AB - Strategies that stimulate the involvement of the community in the National Health System would provide more important role for the city councils in the management and control of public health care. This has currently proven to be difficult due to a new centralism at the Autonomous Community level. In this paper, recent collaborative experiences between municipalities and the National Health System are reviewed. Also, different ways for stimulating a real involvement of city councils in the health care are suggested: from managing new facilities and controlling existing facilities at the primary health care level, to a deep, not merely administrative, inclusion of the local health services into the National Health System. PMID- 1295845 TI - [A proposal to use the median and percentiles vs. the mean in the analysis of PYLL]. PMID- 1295846 TI - Dairy breed bull with complex chromosome translocation: fertility and linkage studies. AB - A chromosome study was performed on the offspring of an American Brown Swiss bull, which was carrier of a complex chromosome translocation. A total of 10 phenotypically normal calves were examined and a similar complex translocation was detected in five calves. The translocation involved identifiable parts of chromosome number one and eight. Furthermore, the terminal band of chromosome one had been translocated to an unidentified chromosome. One of the calves also carried a 1/29 centric fusion chromosome. Pedigree and chromosome analysis showed that the centric fusion originated from another American Brown Swiss bull. A linkage study was performed and an indication of linkage between the Z blood group system and the complex translocation was found. The fertility of the bull was studied, and it was found to have a severely reduced fertility mainly due to an increased rate of early embryonic mortality. PMID- 1295847 TI - Sex chromosome abnormalities in natural populations of the common vole (Microtus arvalis). AB - Four specimens with an aberrant sex chromosome constitution were found in natural populations of the common vole (Microtus arvalis). Two females had an X0 sex chromosome constitution and single males were 2n = 47, XXY and 2n = 47, XYY, respectively. No apparent phenotypical anomalies were recorded in the sex chromosome aneuploids, but their fertility may have been impaired. The incidence of sex chromosome aneuploidy seems to be unusually high in natural populations of the common vole (1.5% of animals examined). Possible explanations for this are discussed. PMID- 1295848 TI - An intriguing Y chromosome in Heteromys anomalus (Rodentia, Heteromyidae). AB - The mitotic chromosomes of the pocket mouse Heteromys anomalus (Rodentia, Heteromyidae) from Venezuela were analyzed by means of conventional staining and various banding techniques. The karyotype of this species is distinguished by a Y chromosome with exceptional banding properties. The very large heterochromatic Y long arm shows a remarkable bright quinacrine fluorescence, but only moderate or dull fluorescence when labeled with other AT base pair-specific fluorochromes. The implications of these findings are discussed. PMID- 1295849 TI - No adaptive response of Chinese hamster ovary cells to low doses of ionizing radiation. AB - Chinese hamster ovary (CHO) cells that had been exposed to very low doses of ionizing radiation from incorporated tritiated thymidine or X-rays were shown not to be more resistant to the induction of chromatid aberrations by a subsequent higher dose of ionizing radiation than previously untreated cells. The adaptive response to ionizing radiation was absent both in cells challenged with high doses of X-rays (1.25 Gy) and in cells post-treated with thermal neutrons (0.5-1 x 10(12) n/cm2). In agreement with these observations in CHO cells we were unable to demonstrate an adaptive response to X-rays also in human lymphocytes from five different donors. PMID- 1295850 TI - A comparison of light intensity preferences for an oviposition site in parthenogenetic and bisexual strains of Drosophila. AB - On the assumption that the survival of a parthenogenetic strain in nature relies on the strain's ability to compete with the bisexual population, we attempted to discern any diminution of competition between bisexual strains of Drosophila and parthenogenetic strains derived from them on the basis of light intensity preferences in choosing an oviposition site. Four different experiential conditions were imposed on each strain prior to testing for light intensity preferences for an oviposition site. Most light responses are significantly different in each strain for the four experiences. There are also significant differences among the bisexual, unisexual and F1 females of a given strain and between strains. Further experiments were performed to determine light preferences during oviposition when unisexual and bisexual females were in direct competition. In only one comparison were their light preferences significantly different. All strains were unique in their overall behavioral spectra. PMID- 1295851 TI - Chromosomal localization of the hormone sensitive lipase (LIPE) and insulin receptor (INSR) genes in pigs. AB - Using rat hormone sensitive lipase (LIPE) and human insulin receptor (INSR) cDNA probes, the LIPE gene was assigned to chromosome 6p11-q21 and the INSR gene to chromosome 2q11-q21 in pigs by in situ hybridization. In humans, these two genes are located on the q and p arms of chromosome 19, respectively. The present results provide the first in situ hybridization mapping data for porcine chromosome 2. PMID- 1295852 TI - Assignment of the bovine immunoglobulin gamma heavy chain (IGHG) gene to chromosome 21q24 by in situ hybridization. AB - By the use of in situ hybridization, the bovine immunoglobulin gamma heavy chain (IGHG) gene was assigned to chromosome 21q24. Fifteen percent of the total grains were scored on chromosome 21, with about 65 percent of these grains located on the q24 band. The present results confirm a previous synteny study and provide the precise chromosomal localization of this gene in the cattle genome. PMID- 1295853 TI - A difference in the proteins found in young adults of inbred strains of Drosophila melanogaster which correlates with genetically-determined, long or short life span. AB - One-dimensional electrophoresis was performed on extracts of flies collected from across all ages. Protein gel patterns were compared for two strains of Drosophila melanogaster with distinctly long and short adult life spans that result from different alleles of longevity genes. An inter-strain difference was observed in the changes in protein pattern in the 77 kDa region in period of day 0-5 after emerging. We propose that the protein involved is a product of autosomal longevity alleles A1 and A2 at the Jm A locus and is related to development of longevity potentials in the preimaginal stage. PMID- 1295854 TI - Purification and characterization of a protein associated with genetically determined longevity difference in Drosophila melanogaster. AB - Earlier studies have shown a correlation between the presence of a 77 kDa protein in the proteins extracted from young adult Drosophila melanogaster (D.m.) and the autosomal longevity allele. A2 at the JmA locus. In this study, a 77 kDa protein has been isolated from pupae of D.m. of a long-lived strain of genotype A2A2, and was purified by DEAE chromatography, ConA column chromatography, and two cycles of gel filtration. The purified protein has a molecular weight of 76,600 (by SDS PAGE), an isoelectric point of pH 6.5, and molar extinction coefficient A(280(1%) = 18.3. It is a glycoprotein containing 3.3% hexose. Supplementing the food of D.m. with the purified protein at 5 x 10(-4) micrograms/ml, beginning at day 5 after emergence, resulted in an increase in the survival rate and maximal life span of both short-lived and long-lived strains of D.m. PMID- 1295855 TI - High frequency of telomeric associations and chromatid exchanges and breaks in human ovarian carcinoma. AB - Cytogenetic analysis of an unselected series of twenty human serous adenocarcinomas and undifferentiated carcinomas of the ovary revealed the presence of telomeric associations (tas) and unstable chromosomal aberrations, including chromatid-type exchanges (cte) and breaks (ctb) in high proportion of tumors studied. Tas and cte & ctb were present in 75% and 55% of tumors, respectively. Involvement of different chromosome telomeres in tas seemed to be random. This is the first report describing telomeric associations in ovarian cancer. Our findings suggest that the frequency of extensive spontaneous chromosome breakage in ovarian carcinoma may be higher than that reported in the literature. PMID- 1295856 TI - Genetic basis of reduced eyes in the hybrids of Drosophila virilis phylad species. AB - Structural anomalies were detected in F1 and backcross hybrids of Drosophila virilis and three of its sibling species Drosophila novamexicana, Drosophila americana texana and Drosophila americana americana. Similar but not identical anomalies have been described in D. virilis x D. lummei hybrids. F1 (D. virilis x D. novamexicana) hybrids had only slight disorders in the abdominal cuticula, but 5.3% of the first backcross generation hybrids had reduced eyes. Eye defects in the second generation were due to interaction of the heterozygous fourth chromosome of D. novamexicana with the homozygous D. virilis chromosomes 2 and 3. Reciprocal F1 hybrids between D. virilis and D. a. americana and between D. virilis and D. a. texana had normal eyes, but in the second hybrid generation 4.9% of D. virilis x D. a. americana and 1.6% of D. virilis x D. a. texana hybrids had anomalous eyes. In D. virilis x D. a. texana hybrids, the heterozygous fourth chromosome of D. a. texana was incompatible with homozygous D. virilis chromosomes 2 and 3. Of the D. virilis x D. a. americana hybrids homozygous for D. virilis chromosomes 2 and 3, 10.2% had the eye defect. The incompatibility system of non-conspecific chromosomes causing the eye anomalies in the hybrids of these three species pairs was different from those in D. virilis x D. lummei hybrids and has evolved independently after the diverging of the American lineage from D. lummei. PMID- 1295857 TI - DNA fingerprints of captive wolves (Canis lupus). PMID- 1295858 TI - Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera. AB - The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened. PMID- 1295859 TI - A morphometric study of histological variations during cellular differentiation of normal human colorectal epithelium. AB - Quantifiable variations existing in the colorectal crypt during cellular differentiation were detected by using simple computer-aided morphometric techniques applied to routinely prepared H&E stained and semithin toluidine blue stained sections of normal colonic mucosa. Generally, most of the morphometric parameters including nuclear volume, nuclear volume weighted mean volume, cytoplasmic volume, cellular volume, nuclear axial ratio (a/b), mean nuclear diameter, nuclear shape factor (NSF) and nuclear maximum angle (Agmax) showed an increasing trend between basal and surface segments. Conversely, the nuclear cytoplasmic (N/C) ratio, NSF and nuclear circularity index (NCI) decreased between these segments. Epithelial cells in the basal segment had the highest N/C ratio and the lowest cell volume due to their low volumes of cytoplasm. However, substantial increases of cytoplasmic volume occurred in the intermediate segment, thereby expanding the cell volume to 136% of that of the basal segment cell. Data for a/b, NSF, NCI and Agmax suggest that the epithelial nuclei were more ellipsoidal in shape and were aligned more perpendicular to the basement membrane as they reached the surface epithelium. Numerical densities for epithelial cell nuclei were highest in the basal segment, indicating more nuclear profiles at this region per unit area or volume. This also suggested that the basal segment was the active proliferating zone. Such observations agree with previously reported cell kinetic and autoradiographic studies. PMID- 1295861 TI - Lymph pathways associated with Peyer's patches in sheep. AB - Lymphatic drainage of the ileum associated with Peyer's patches begins with lymph entering a single lacteal of the villus, probably through intercellular flaps, which prevent retrograde flow to the interstitium. These lacteals are continuous with an interconnecting plexus of branching sinuses which surrounds the crypts and follicle domes in the lamina propria. Small vessels emanating from this plexus penetrate the muscularis mucosa, where lymph can either flow within septal vessels to the deep submucosa, or enter the follicular sinuses to move freely around follicles, and through gaps in septal walls. All lymph enters a deep submucosal network where retrograde flow is prevented by valves. Lymph is then conveyed through vessels passing between the fibres of the muscularis externa to other lymphatics, which transport lymph from the ileal surface to the mesenteric nodes. PMID- 1295860 TI - A fractionator study of the effects of undernutrition during early life on rat Purkinje cell numbers (with a caveat on the use of nucleoli as counting units). AB - The effects of varying periods of general protein-calorie undernutrition during early life on Purkinje cells in the cerebellum of the rat were examined. In Experiment 1, animals were undernourished from d 18 of gestation until either d 30 or d 60 of postnatal age, followed in some cases by a period of nutritional rehabilitation. In Experiment 2, rats were undernourished from conception until d 30 postnatally, followed by a period of rehabilitation until 60 d of age. The 'fractionator' method was employed to estimate the total number of cerebellar Purkinje cell nucleoli. If each cell has one nucleolus, this number is equal to the number of Purkinje cells. In Experiment 1, the estimated mean number of Purkinje cell nucleoli varied between 188,000 and 273,000 for the groups of animals studied. However, the interanimal variation was large and 2-way analysis of variance tests failed to reveal any statistically significant age, nutrition or interaction effects. In Experiment 2, rats killed immediately after the period of undernutrition possessed significantly fewer Purkinje cell nucleoli than age matched controls. This did not represent a real decrease in cell number. Instead, the result could be explained by a change of Purkinje cell morphology in undernourished rats. The change included nucleolar regression. Nutritionally rehabilitated animals had similar numbers of nucleoli to control rats. It is concluded that the levels and periods of undernutrition used in these experiments did not affect significantly the total numbers of cerebellar Purkinje neurons. PMID- 1295862 TI - Modification of lectin binding in rat gut mucosa during experimental cholestasis. AB - Glycoconjugate distribution on rat gut mucosa has been studied by using peroxidase-labelled lectins (Lotus tetragonolobus, Dolichos biflorus, Arachis hypogaea and Glycine max) after surgical interruption of the common bile duct. Specimens from cholestatic rats were compared with sham-operated (simple laparotomy) and normal controls to determine which of the observed modifications could be due either to the operation itself or to the cholestasis. Most of the modifications occurred in the duodenum. The operation itself modified some binding properties. Lotus tetragonolobus binding extended both in cholestatic and in sham-operated rats, but returned to normal levels earlier in sham-operated than in cholestatic rats. Conversely, cholestasis induced (1) almost total loss of Arachis hypogaea binding in the Golgi zone of superficial duodenal goblet cells; (2) an increase at the 14th postoperative day of Dolichos biflorus binding in the cytoplasmic calyx of goblet cells which then diminished up until the 28th day; and (3) an increase of Glycine max binding in the Golgi zone of goblet cells. PMID- 1295863 TI - The intraglandular submandibular ganglion of postnatal and adult rats. II. A morphometric and quantitative study. AB - A morphometric study was undertaken on the submandibular ganglion cells in rats of different ages. This showed a direct proportional increase with age in all the variables measured. Mean cross-sectional cell area showed the most dramatic growth, an increase of more than 5-fold between birth and young adulthood. Mean cell diameter and cell perimeter doubled over the same period. The growth of the nucleus, expressed as diameter, was slower when compared with that of the ganglion cells as a whole. The number of intraglandular ganglion cells remained relatively unchanged from birth to young adulthood, ranging from about 3000 to 5000 cells. They were mainly distributed at the hilar region of the submandibular salivary gland, contributing 1/2 to 2/3 of the total ganglion cell population. The second largest cell population was in the intralobular region, which made up about one-third of the population. The least populated region was in the connective tissue of the sublingual salivary gland, which contained only about 5 7% of the total cell number. Cell counts based on the fluorogold labelling method were generally lower than those made after haematoxylin and eosin staining. In the 2-d-old animals, counts of fluorogold-labelled cells were only about half the H & E counts. The discrepancy may be due to the thicker sections used in the fluorogold method, superimposition of cells leading to an underestimation of cell numbers. Nevertheless, the fluorogold labelling method provided rapid and reproducible results. Its main advantage is that the labelled ganglion cells emit a bright yellow fluorescence which is readily identified; the other is the simplicity of the procedure, as labelling of ganglion cells can be achieved by the intraperitoneal route. PMID- 1295864 TI - Growth of the ribs at the costochondral junction in the rat. AB - The in situ growth of the ribs at the costochondral junction was examined by 2 methods. In the first, 3 threads were tied around the 5th, 6th or 7th ribs of 20 d-old rats. The first thread was located around the bony part of the rib close to the costochondral junction, the second around the cartilaginous part the same distance away from the junction, and the third also around the cartilaginous part but further away. The distances between the threads were measured at 20 and 40 d and were found to have increased considerably. In the second part, an immunohistochemical method using bromodeoxyuridine was employed to detect proliferating cells at the costochondral junction. The most active cell proliferation was observed in the proliferative zone, but mitoses were also noticed in the germinative zone. The results provide further evidence that the growth potential of costochondral grafts used in reconstructive surgery is related to the length of their cartilaginous portion. PMID- 1295865 TI - Elucidation of aspects of murine skeletal muscle regeneration using local and whole body irradiation. AB - To investigate the role of proliferating local and emigrating circulatory leucocytes in skeletal muscle regeneration in mice, their bone marrow was ablated with whole body irradiation and compared with the effects of local irradiation. The results indicate that (1) the sealing of damaged myofibres is a function of local cells and is not dependent on the presence of infiltrating leucocytes; (2) the formation of sarcoplasmic projections at the ends of damaged myofibres is dependent on leucocyte infiltration; (3) nuclei in the sarcoplasmic projections are probably derived from fusion of muscle precursor cells; (4) most muscle precursor cells in vivo replicate at least once before fusion; and (5) both replication and fusion of muscle precursors can occur in the absence of infiltrating leucocytes. These results are discussed with respect to the interaction of various cell populations during regeneration of skeletal muscle, and are of clinical significance to pathological changes seen in many myopathies. PMID- 1295866 TI - Behaviour of osteoclasts in vitro: contact behaviour of osteoclasts with osteoblast-like cells and networking of osteoclasts for 3D orientation. AB - The cell-cell contact-induced behaviour of osteoclasts and osteoblasts in vitro was investigated by time-lapse videomicroscopy. Contact interactions of osteoclasts with autologous cells, derived mostly from chick but also from rat bones, included contact inhibition, failure of contact inhibition, contact guidance along stabilised edges of other cells, and underlapping of other cells. Message-mediated contact behaviour (MMCB) between osteoclasts and autologous osteoblastic cells resulted, after a time delay, in zeiosis of the osteoblast like cell which could continue, or even begin, after the osteoclast broke contact, leading to retraction of the cell and occupation of its position by the osteoclast. MMCB may play a part in the breaching of the osteoblastic sheet by osteoclasts and, in general, in the malignant spread of neoplastic cells. Two or more osteoclasts were often joined by connecting and coordinating tubules (CCTs) of varied, and varying, lengths and widths. Osteoclasts could travel along the CCTs in both directions, or send nuclei through them. The CCTs became temporarily attached to the surface of other cells, or to the substrate, then acting as a temporary anchorage for orientation and for the return of the cell to the same spot. The dynamics of osteoclastic behaviour suggest that such a networking of osteoclasts is valuable for the 3D coordination of their role in bone turnover. PMID- 1295867 TI - Calcium phosphate crystal distribution in the superficial zone of human femoral head articular cartilage. AB - The distribution of cuboid crystals in articular cartilage was examined by image analysis of electron micrographs. The specimens were considered to be functionally normal articular cartilage from femoral heads resected either because of femoral neck fracture or tumour in the distal femur. The study was restricted to the superficial region between 0 and 50 microns depth. Crystals were present in all specimens regardless of the age of the patient. The crystal profile area density was significantly greater in superior region samples than inferior region samples and this difference was less in older specimens. A band of microcrystals 10-20 microns below the articular surface was observed in superior samples. A significant correlation between mean individual crystal profile area and age was observed. It is noted that crystals are present in regions of cartilage subject to high mechanical stress. PMID- 1295868 TI - Zonal differentiation of the marmoset (Callithrix jacchus) endometrium. AB - The differentiation of the marmoset (Callithrix jacchus) endometrium under different steroid hormone levels was investigated by electron microscopy and by the binding of different antibodies directed against collagen types. Based on differences in the glandular and interglandular compartments, the endometrium of sexually mature common marmosets consists of 3 zones: basal, adluminal and luminal. Hormone-dependent appearances are characterised. With low steroid concentrations, intercellular spaces between glandular epithelial cells occurred in the adluminal and the luminal areas. Epithelial cells of the basal region exhibited coated pits and phagolysosomes together with large apical protrusions. Under oestrogen dominance, phagolysosomes, fat vesicles and apical protrusions were evident in epithelial cells in the adluminal region. Secretory granules and concentric glycogen accumulations were a characteristic feature in epithelial cells of the adluminal and basal regions. With high progesterone concentrations, large empty vesicles were found with a higher frequency in adluminal than in basal epithelial cells. Using FITC-labelled antibodies against types V and VI collagen, binding was apparent adluminally in close vicinity to basement membranes, whereas reactivity was seen in the entire interglandular region of the basal area during this phase. Our findings indicate specific microenvironments with distinctive structural characteristics in the marmoset endometrium that are hormone dependent during all phases of the endometrial cycle. They are not related to menstruation, appear to be characteristic for primates and could reflect epithelial-mesenchymal interaction. PMID- 1295869 TI - In vivo interaction of cationised ferritin with the surface coat and endocytosis by pulmonary intravascular macrophages: a tracer kinetic study. AB - The pulmonary intravascular macrophages (PIMs) of goat lung contain a unique electron-dense coat consisting of globular units arranged in a linear fashion along the cell surface. The globules showed a high affinity for cationised ferritin (CF) within 2-5 min of its intravenous injection, whereas native ferritin did not bind with the globules of the coat. The CF-labelled (hybrid) globules were subsequently internalised via receptor-mediated endocytosis. During 2-5 min of CF treatment, hybrid globules rapidly reached endosomes, multivesicular bodies and lysosomes, which acquired a high visibility in the form of interconnected tubular structures in the area of the Golgi complex. It is suggested that globular units of the surface coat, by showing high affinity for CF, resemble negatively charged large low density lipoprotein molecules. It supports our earlier postulate that heparin and lipolytic lipase sensitive globules of the surface coat of PIMs may be composed of lipoprotein-like substances. The ubiquity of the surface coat as a differentiated surface structure perhaps enables PIMs to cope with a barrage of stimulatory and suppressive signals within the microcirculatory units of the lungs of these animals. PMID- 1295870 TI - Fibre type composition of the soleus muscle in hypoxia-acclimatised rats. AB - Fibre type composition in the soleus muscle was studied in second generation male and female Sprague-Dawley rats bred at 460 Torr (hypobaric hypoxia). In control male and female rats (bred at sea level atmospheric pressure) the percentage of slow twitch oxidative (SO) fibres increased, and the percentage of fast twitch oxidative glycolytic (FOG) fibres decreased over time. In male hypoxic rats fibre type composition did not change. However, in female hypoxic rats the percentage of SO fibres increased, and that of FOG fibres decreased over time. The female hypoxic rats had a higher percentage of FOG fibres and a lower percentage of SO fibres than age-matched control rats. These findings indicate that hypoxia acclimatised rats have a relatively high percentage of FOG fibres, and that this is due to inhibition of the fibre type shift from FOG to SO, which occurs during normal development. Furthermore, there is a sex-related difference in the change in fibre type composition in hypoxia-acclimatised rats. PMID- 1295871 TI - Comparative study of renin expression in the coagulating glands of C57BL/6 and Balb/c mice. AB - The comparative localisation of renin in the genital organs, especially in the coagulating glands of male mice of the strains C57BL/6 and Balb/c, was investigated using immunocytochemical, immunoelectron microscopical and Northern blot techniques. Dot-like reactions for renin, of varying diameters, were detected immunocytochemically in the epithelial cells of coagulating glands of C57BL/6 mice, but not in those of Balb/c mice. In both strains, many electron dense granules differing in content and morphology were observed in the epithelial cells of the coagulating glands. Crystalline materials were sometimes contained in these granules. Colloidal gold particles indicating the presence of renin were detected in the electron dense granules of C57BL/6 mice, in which they showed a heterogeneous distribution and were especially located on the crystalline structure. No positive reaction was detected in these crystalline structures in Balb/c mice. Renin mRNA was detected in the coagulating glands of both C57BL/6 and Balb/c mice by Northern blot analysis. However, the expression in C57BL/6 coagulating glands was stronger than that in Balb/c. These findings suggest that renin is synthesised and released in the coagulating glands. PMID- 1295872 TI - Lanthanum tracer and freeze-fracture studies suggest that compartmentalisation of early bone matrix may be related to initial mineralisation. AB - In adult bone the calcified matrix and enclosed osteocytes are separated from the extracellular space by a continuous layer of bone lining cells. It thus appears that bone matrix is compartmentalised and, as such, may constitute a 'milieu interieur' which is different from the general extracellular space. Since adult bone matrix is compartmentalised and matrix vesicles also form a microcompartment, it is conceivable that compartmentalisation, in early osteogenesis, may be a requirement for the initial events of the mineralisation process. We have therefore conducted an ultrastructural, tracer, and freeze fracture study to determine the stage in which bone matrix becomes compartmentalised and also to find out whether there are tight junctions between osteoblasts. The results show that in early nonmineralised stages and in incipient mineralisation, lanthanum penetrates all intercellular spaces and the newly forming bone matrix which is rich in matrix vesicles and collagen. With the progression of mineralisation, when all matrix vesicles appear mineralised and calcification is 'spreading' to the surrounding matrix, lanthanum is restricted to intercellular spaces and conspicuous macular tight junctions are present between osteoblasts. We suggest that matrix vesicles act as microcompartments for calcification when the early bone matrix is in continuity with the surrounding extracellular space. In later stages, when lanthanum fails to penetrate the matrix, matrix vesicles may no longer be necessary because the bone matrix itself is compartmentalised, thus allowing for localised changes in composition that might favour mineral deposition. PMID- 1295874 TI - Leydig cells in the lingual epithelium of the axolotl, Ambystoma mexicanum, are immunoreactive for serotonin. AB - The Leydig cells in the lingual epithelium of the axolotl were investigated by immunohistochemistry using serotonin antiserum. Serotonin-immunoreactivity was found in their secretory granules. The physiological role of serotonin in the Leydig cell, a type of exocrine cell, is unknown. PMID- 1295873 TI - Quantitative analysis of rough endoplasmic reticulum in chondrocytes of articular and tracheal cartilage of rabbits following the systemic administration of hydrocortisone. AB - The rough endoplasmic reticulum (RER) in chondrocytes was analysed stereologically in articular cartilage of knee joints and in tracheal cartilage of rabbits injected intramuscularly with 5 mg/kg hydrocortisone daily for 4 wk. In articular cartilage, RER area per unit cytoplasmic volume decreased in chondrocytes in all (superficial, middle and deep) zones, although the volume of glycogen deposits per unit cytoplasmic volume increased in the middle and deep zones. RER area per chondrocyte also decreased in the 3 zones without changes in average chondrocyte volume in the superficial and deep zones. Furthermore, the volume of glycogen deposits per chondrocyte did not alter in the 3 zones. These indicate a reduction of RER area in articular chondrocytes after hydrocortisone administration and suggest a decrease in the protein-synthesising capacity of these cells. In tracheal cartilage in which 2 zones were identifiable, RER area per unit cytoplasmic volume decreased in chondrocytes in both the superficial and main zones without changes in the volume of glycogen deposits per unit cytoplasmic volume. In addition, RER area per chondrocyte decreased in the main zone. The results suggest that the decrease in RER area in chondrocytes after corticosteroid administration is not specific to articular cartilage but is common to cartilage in various organs. PMID- 1295875 TI - Magnetic resonance imaging of the saccular otolithic mass. AB - The frog's inner ear was studied in vivo by high spatial resolution magnetic resonance imaging at 7 Tesla. The vestibule, the internal acoustic meatus, and the auditory tube have been identified. The large otolithic mass contained in the vestibule showed a virtual absence of magnetic resonance signal probably due to its composition of closely packed otoconia. PMID- 1295876 TI - Does the anatomical location of a muscle affect the influence of undernutrition on muscle fibre number? AB - Nutritional restriction during muscle fibre number development invariably has a more detrimental effect on the biceps brachii than on the soleus. The difference may be due to the relative proportions of fibre types in the muscles or the anatomical location of the muscles. To distinguish between the effects of location and fibre type the biceps (fast, cranial and proximal), soleus (slow, caudal and distal), and extensor digitorum longus (EDL) (fast, caudal and distal) were examined from control and undernourished guinea pig neonates. A 40% reduction in maternal intake resulted in a reduction in neonate body and muscle weights (P < 0.005), biceps (P < 0.05) and EDL fibre numbers (P < 0.005), but did not affect soleus fibre number. At birth the ratio of fast fibres to slow was 7.5 for the biceps, 7.0 for the EDL, and 1.5 for the soleus. The effect of undernutrition on muscle fibre number therefore seems to be a function of the fibre types in that muscle. PMID- 1295877 TI - A teaching model to illustrate the variation in size and shape of the maxillary sinus. AB - A technique to produce teaching models of the maxillary sinus is described. Dental impression material is injected into the maxillary sinus of a cadaver and subsequently dissected out. Using an impression and mould technique in a series of steps, a stone model of the maxillary sinus is produced. The shape, size and configuration of the model can be seen and the dimensions measured. A radiopaque impression material can be used so that the radiographic outline of the maxillary sinus on standard radiographic projections can be shown. Models of both dentate and edentulous patients can be used to show anatomical variation and the relationship to teeth and are useful in teaching both gross and radiographic anatomy. Since 10 out of 11 specimens had 3 walls leading to the apex from a 4 sided base, it would appear that the classical description of a 4-sided pyramidal shape to the maxillary sinus is relatively uncommon. PMID- 1295878 TI - Undergraduate medical anatomy teaching. PMID- 1295879 TI - Site-directed mutagenesis of amino acid residues involved in the glutathione binding of human glutathione S-transferase P1-1. AB - The four residues of human glutathione S-transferase P1-1 whose counterparts were indicated by X-ray crystallography to reside in the GSH-binding site of pig glutathione S-transferase P1-1 were individually replaced with threonine or alanine by site-directed mutagenesis to obtain mutants R13T, K44T, Q51A, and Q64A. The kinetic parameters, susceptibilities to an inhibitor, S-hexyl-GSH, and affinities for GSH-Sepharose of the latter were compared with those of the wild type enzyme, and pKa of the thiol group of GSH bound in R13T was shown to be equivalent to that in the wild type. From the results, Lys44, Gln51, and Gln64 were deduced to contribute to the binding of GSH. On the other hand, Arg13 seems to be essential for the enzymatic activity as mainly involved in the construction of a proper structure of the active site. PMID- 1295880 TI - Major ATPases on clofibrate-induced rat liver peroxisomes are not associated with 70 kDa peroxisomal membrane protein (PMP70). AB - We previously reported that novel Mg(2+)-ATPases were induced in rat liver peroxisomes by clofibrate administration and that these activities consisted of at least two types of enzymes, N-ethylmaleimide (NEM)-sensitive and -resistant. Here we present evidence that neither of these major peroxisomal ATPases is associated with the 70-kDa peroxisomal membrane protein (PMP70), because: (i) proteinase K treatment of peroxisomes resulted in inactivation of only NEM sensitive ATPase, whereas disappeared PMP70 completely; (ii) NEM-sensitive ATPase activity was barely immunoprecipitated with anti-PMP70 IgG; (iii) the solubilized ATPases behaved differently from PMP70 on native PAGE; and finally (iv), the major peroxisomal ATPases were separated from PMP70 on gel filtration chromatography. PMID- 1295881 TI - Chain length distribution of the products formed in solanesyl diphosphate synthase reaction. AB - Factors that affect the termination of isoprenoid chain elongation catalyzed by prenyltransferase were investigated. The chain-length distribution of reaction products of solanesyl diphosphate synthase [EC 2.5.1.11] homogeneously purified from Micrococcus luteus changed dramatically according to the concentration of the complex formed between isopentenyl diphosphate and Mg2+ (IPP-Mg) in the reaction mixture. However, the concentration of the complex between farnesyl diphosphate and Mg2+ (FPP-Mg), the priming substrate for this synthase, did not affect the product distribution, provided that the concentration of IPP-Mg was maintained at a certain level. Thus, the level of IPP-Mg is decisive in affecting the chain length distribution of the products of the prenyltransferase reaction, and the Mg(2+)-dependent variability of product specificity so far observed can now be understood in terms of the effect of IPP-Mg concentration. PMID- 1295882 TI - Inhibition of sarcoplasmic reticulum Ca(2+)-ATPase by 2,5-di(tert-butyl)-1,4 benzohydroquinone. AB - We characterized the interaction of 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) with the sarcoplasmic reticulum (SR) Ca(2+)-ATPase from rabbit fast twitch skeletal and canine cardiac muscles by examining the effect of this agent on the ATPase reaction. tBuBHQ at less than 10 microM inhibited ATP hydrolysis by both isoforms of Ca(2+)-ATPase by up to 80 and 90%, respectively. The half maximal inhibition of these enzymes was observed at about 1.5 microM tBuBHQ. Thus, this agent potently inhibits the fast-twitch skeletal and slow-twitch skeletal/cardiac isoforms of SR Ca(2+)-ATPase. tBuBHQ at 5-10 microM inhibited the rate of decomposition of the phosphoenzyme intermediate (EP), measured as a ratio between ATPase activity and the EP level in the steady state, by 35-40%. It also inhibited formation of EP by decreasing the rate of Ca2+ binding to the Ca(2+)-deficient, nonphosphorylated enzyme to about 1/8 of the control value. These results indicate that tBuBHQ has at least two sites of action in the reaction sequence for the SR Ca(2+)-ATPase. PMID- 1295883 TI - Preferential activation of phospholipase A2 by low concentrations of phosphatidic acid with long-chain fatty acids in rabbit platelets. AB - The role of phosphatidic acid (PA) in the signal transduction system of platelets was studied using 1-stearoyl 2-arachidonoyl PA (PASA). When PASA was added to rabbit platelets, aggregation occurred. BW755C, a dual inhibitor of cyclooxygenase and lipoxygenase, as well as p-bromophenacyl bromide and mepacrine, inhibitors of phospholipase A2, inhibited the aggregation induced by low concentrations of PASA, but not that induced by high concentrations. PASA also stimulated, in a dose-dependent manner, arachidonic acid liberation, lysophosphatidylcholine and diacylglycerol formation, and mobilization of intracellular Ca2+; all of which were dependent on the presence of Ca2+ in the outer medium. The arachidonic acid liberation was inhibited by p-bromophenacyl bromide or mepacrine, while diacylglycerol formation by low concentrations of PASA was inhibited by BW755C. With platelet membrane fractions or with the platelets made permeable to Ca2+ by pretreatment with ionomycin, PASA caused arachidonic acid liberation in the presence of Ca2+. Furthermore, PASA enhanced the activity of phospholipase A2 partially purified from platelet cytosol acting on 1-palmitoyl-2-[14C]arachidonoyl-glycerophosphoethanolamine. These results provide evidence that PASA preferentially potentiates the activation of phospholipase A2 in cooperation with Ca2+, suggesting that PA acts as a positive feedback regulator to potentiate the activation of phospholipase A2 and contributes to the amplification of platelet activation. PMID- 1295884 TI - Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. AB - Mitoxantrone, a new anthraquinone, showed inhibitory an effect on protein kinase C (PKC) activity. Its IC50 value was 4.4 micrograms/ml (8.5 microM), which is much lower than those of the well-known anthracyclines daunorubicin and doxorubicin, the IC50 values of which are more than 100 micrograms/ml (> 170 microM). Kinetic studies demonstrated that mitoxantrone inhibited PKC in a competitive manner with respect to histone H1, and its Ki value was 6.3 microM (Ki values of daunorubicin and doxorubicin were 0.89 and 0.15 mM, respectively), and in a non-competitive manner with respect to phosphatidylserine and ATP. Inhibition of phosphorylation by mitoxantrone was observed with various substrates including S6 peptide, myelin basic protein and its peptide substrate derived from the amino-terminal region. Their IC50 values were 0.49 microgram/ml (0.95 microM), 1.8 micrograms/ml (3.5 microM), and 0.82 microgram/ml (1.6 microM), respectively. Mitoxantrone did not markedly inhibit the activity of cyclic AMP-dependent protein kinase, casein kinase I or casein kinase II, at concentrations of less than 10 micrograms/ml. On the other hand, brief exposure (5 min) of HL60 cells to mitoxantrone caused the inhibition of cell growth with an IC50 value of 52 ng/ml (0.1 microM). In HL60 cells, most of the PKC activity (about 90%) was detected in the cytosolic fraction. When HL60 cells exposed to 10 micrograms/ml mitoxantrone for 5 min were observed with fluorescence microscopy, the fluorescence elicited from mitoxantrone was detected in the extranuclear area. These results indicated that mitoxantrone is a potent inhibitor of PKC, and this inhibition may be one of the mechanisms of antitumor activity of mitoxantrone. PMID- 1295886 TI - Calcium-induced fragmentation of skeletal muscle nebulin filaments. AB - When chicken breast muscle myofibrils were treated with a solution containing 0.1 mM CaCl2 and 30 micrograms of leupeptin/ml, nebulin filaments were fragmented into 200-, 180-, 40-, 33-, and 23-kDa subfragments. All the subfragments except the 180-kDa one were released from the myofibrils. The fragmentation of nebulin filaments seems to be induced by the binding of large amounts of calcium ions. Similar changes took place in nebulin filaments in post-mortem skeletal muscle. It has been proposed that nebulin co-exists with thin (actin) filaments and participates in stabilizing their organization [Wang, K. & Wright, J. (1988) J. Cell Biol. 107, 2199-2212]. Thus, the above result suggests that Ca-induced fragmentation of nebulin filaments destabilizes the organization of thin filaments and is a key factor in meat tenderization during post-rigor aging. PMID- 1295885 TI - Purification and characterization of two casein kinases from ejaculated bovine spermatozoa. AB - Two protein kinases active on casein and phosvitin were partially purified from the soluble fraction of ejaculated bovine spermatozoa. They were operationally termed casein kinase A and B based on the order of their elution from a phosphocellulose column. CK-A showed an approximate molecular mass of 38 kDa, and it phosphorylated serine residues of casein and phosvitin utilizing ATP as a phosphate donor (Km 19 microM). Enzyme activity was maximal in the presence of 10 mM MgCl2, whereas it decreased in the presence of spermine, polylysine, quercetin, and NaCl (20-250 mM). CK-B seemed to have a monomeric structure of about 41 kDa; it underwent autophosphorylation and cross-reacted with polyclonal antibodies raised against recombinant alpha, but not beta, subunit of human type 2 casein kinase. It phosphorylated both serine and threonine residues of casein and phosvitin, utilizing ATP (Km 12 microM) but not GTP as a phosphate donor. Threonine was more affected in the phosphorylated phosvitin than in the partially dephosphorylated substrate. CK-B was active toward the synthetic peptide Ser (Glu)5 and calmodulin (in the latter case, in the presence of polylysine), and it was activated by spermine, polylysine, MgCl2 (30 mM), and NaCl (20-400 mM). The activity of the enzymes was not affected by cAMP, or the heat-stable inhibitor of the cAMP-dependent protein kinase, or calcium. PMID- 1295887 TI - Purification and characterization of nebulin subfragments produced by 0.1 mM CaCl2. AB - Nebulin, which forms a long inextensible filament in sarcomeres, was fragmented into 200-, 180-, 40-, 33-, and 23-kDa subfragments on treatment with 0.1 mM CaCl2. The subfragments released from myofibrils were successfully purified by immunoaffinity column chromatography. The 200-, 40-, 33-, and 23-kDa subfragments were released from myofibrils and occupied 80% of the nebulin filaments. The remainder comprised the 180-kDa subfragment bound to the myofibrils. There is a possibility that an entire nebulin filament is constructed from the 200-, 180-, 40-, 33-, and 23-kDa subfragments. We have developed a new "fluorescence-method" to detect the binding of calcium ions to a protein using quin2, and clarified that nebulin is a calcium-binding protein, and that calcium ions bind to the 200 , 40-, and 23-kDa subfragments. Nebulin filaments are probably fragmented on the binding of large amounts of calcium ions to the 200-, 40-, and 23-kDa subfragments. PMID- 1295888 TI - Site of attachment of mercuribenzoate in crystals of an actin:DNase I complex. AB - Crystals of a complex of chicken gizzard G-actin and DNase I were soaked in a solution of radioactive 4-hydroxymercuribenzoate (MB). The soaked crystals, which contained 0.93 mol of MB per mol of G-actin, were dissolved in "G-buffer" and digested with trypsin, and the resulting peptides were fractionated by thin-layer chromatography. The MB is exchangeable between peptides that contain cysteine residues, but the data obtained here suggested that MB attached to the cysteine residue at the 373rd position of the G-actin molecule. PMID- 1295889 TI - Preparation and characterization of troponin C from bullfrog skeletal muscle. AB - Troponin C was isolated from the skeletal muscle of bullfrog (Rana catesbeiana), and its relative molecular mass was estimated to be 18,000 by SDS/polyacrylamide gel electrophoresis. In its amino acid composition, bullfrog troponin C was similar to that of the frog (Rana esculenta) but different from that of rabbit. Its ultraviolet spectrum was consistent with its amino acid composition. The ultraviolet difference spectrum of the Ca(2+)-loaded form vs. the metal-free form indicated that the single Tyr residue and some Phe residues in the bullfrog troponin C molecule were affected by the conformational change associated with Ca2+ binding. On electrophoresis in polyacrylamide gel in 14 mM Tris and 90 mM glycine, the metal-free and Mg(2+)-loaded forms migrated slower than the Ca(2+) loaded form. The property is shared by rabbit troponin C but not parvalbumins or calmodulin. The ATPase activity of CDTA-treated myofibrils reconstituted with bullfrog troponin C showed the same Ca(2+)- and Sr(2+)-sensitivity as that of those reconstituted with rabbit troponin C. Bullfrog troponin C is, thus, physiologically the same as rabbit troponin C, in spite of several marked differences in their physicochemical properties. PMID- 1295891 TI - Further studies on aspartate aminotransferase of thermophilic methanogens by analysis of general properties, bound cofactors, and subunit structures. AB - Aspartate aminotransferase (AspAT) [EC 2.6.1.1] of thermophilic methanogen was further characterized with the enzyme from Methanobacterium thermoautotrophicum strain FTF-INRA as well as M. thermoformicicum strain SF-4. AspAT of strain FTF INRA was similar in the amino donor specificity to the enzyme of M. thermoformicicum strain SF-4, in that it was active on L-cysteine and L-cysteine sulfinate in addition to L-glutamate and L-aspartate. The enzymes gave similar absorption spectra having maxima at around 326 and 415 nm with no pH-dependent shift but were found to contain 1 mol of tightly bound pyridoxal 5'-phosphate (PLP) per subunit. Reconstitution of each apoenzyme with added PLP resulted in partial recovery of the original enzymatic activity, suggesting a significant conformational change of the active site region upon removal of the cofactor. Polyacrylamide gel electrophoresis (PAGE) and gel filtration analyses revealed a tetrameric structure (180 kDa) of identical subunits with a molecular mass of 43 kDa for each of these enzymes. Electric current was found to affect the interaction or affinity of each subunit, promoting dissociation of the native enzyme into the monomeric form. Alkaline treatment was effective only for dissociation of the enzyme from strain SF-4. They were distinguishable by the more rapid reassociation of the monomer to the native aggregated form in the enzyme of strain FTF-INRA. PMID- 1295890 TI - The binding of adenine nucleotides to apo-electron-transferring flavoprotein. AB - Apoprotein of electron-transferring flavoprotein (ETF) reacts with FAD as follows: A*<-->A, A+FAD<-->holoETF. Two different forms of apoETF (A* and A) convert into each other and only one of them, A, can associate with FAD [Sato, K. et al. (1991) J. Biochem. 109, 734-740]. In the present study, the reactions between apoETF and ATP, ADP, AMP, riboflavin, or FMN were investigated. It was revealed that all three adenine nucleotides bind with apoETF with the same kinetic reaction scheme as FAD, and compete with FAD. These results suggest that the nucleotides bind to A with the same location as the ADP part of FAD in holoETF and that the ADP-binding site of apoETF is generated upon conversion from A* to A. Neither riboflavin nor FMN bound to apoETF regardless of the presence or absence of the nucleotides, indicating that the ADP part of the FAD molecule is essential to the incorporation of the isoalloxazine ring into ETF. The binding rate constant of FAD to A was 1/20 of that of ADP while the dissociation rate constant was 1/1,000. This indicates that the riboflavin part of FAD inhibits the binding of FAD by steric hindrance, while after the binding, it stabilizes the complex. PMID- 1295892 TI - Isolation and characteristics of scallop sarcoplasmic reticulum with calcium transport activity. AB - Sarcoplasmic reticulum with calcium transport activity has been isolated from the cross-striated adductor muscle of the scallop, which lives in cold (< or = 20 degrees C) sea water, by using pH 7.0 buffer solution both to homogenize the tissue and to sediment the membrane fraction. The yield of the preparation was 60 100 mg protein from 100 g of the scallop muscle. Ca(2+)-activated ATPase protein of about 100 kDa accounted for 40-50% of the protein preparation. The maximum activities of ATP-dependent, oxalate-facilitated calcium accumulation and Ca(2+) ATPase were observed at a pH of about 7.0 and temperature of 20-30 degrees C, and their values were about 2 mumol Ca2+/mg of protein/min and about 3 mumol ATP hydrolysis/mg of protein/min, respectively. At 0 degree C, 10-20% of these activities was maintained, while at 37 degrees C, the activities were irreversibly lost. The Ca(2+)-ATPase activity was half-maximally activated at about 0.3 microM [Ca2+]. The ATPase activity exhibited non-Michaelian behavior with respect to ATP, with two different Km values of approximately 10 microM and 0.1-0.3 mM. GTP, CTP, and ITP were also hydrolyzed by the preparation at a rate of 10-30% of that of ATP. The preparation was stored at -80 degrees C with retention of function for about a year. PMID- 1295893 TI - Modification of pig liver dimeric dihydrodiol dehydrogenase with diethylpyrocarbonate and by rose bengal-sensitized photooxidation: evidence for an active-site histidine residue. AB - Dihydrodiol dehydrogenase from pig liver was inactivated by diethylpyrocarbonate (DEP) and by rose bengal-sensitized photooxidation. The DEP inactivation was reversed by hydroxylamine and the absorption spectrum of the inactivated enzyme indicated that both histidine and tyrosine residues were carbethoxylated. The rates of inactivation by DEP and by photooxidation were dependent on pH, showing the involvement of a group with a pKa of 6.4. The kinetics of inactivation and spectrophotometric quantification of the modified residues suggested that complete inactivation was caused by modification of one histidine residue per active site. The inactivation by the two modifications was partially prevented by either NADP(H) or the combination of NADP+ and substrate, and completely prevented in the presence of both NADP+ and a competitive inhibitor which binds to the enzyme-NADP+ binary complex. The DEP-modified enzyme caused the same blue shift and enhancement of NADPH fluorescence as did the native enzyme, suggesting that the modified histidine is not in the coenzyme-binding site of the enzyme. The results suggest the presence of essential histidine residues in the catalytic region of the active site of pig liver dihydrodiol dehydrogenase. PMID- 1295894 TI - Inhibition of dimeric dihydrodiol dehydrogenase by 4-hydroxyphenylketone derivatives: aspects of inhibitor structure and binding specificity. AB - Dimeric dihydrodiol dehydrogenases from pig liver, monkey kidney, and rabbit lens were inhibited more potently by 4-hydroxyphenylketones such as 4 hydroxybenzaldehyde, 4-hydroxyphenylglyoxal, and 4-hydroxyacetophenone than by isoascorbate and ascorbate, known inhibitors of the enzymes. No significant inhibition was observed with 2- or 3-hydroxyphenylketones, phenylketones with a functional group other than a hydroxy group at the 4-position, and 4 hydroxyphenyl derivatives without a carbonyl group. The steady-state kinetic analyses of the inhibition of the pig liver enzyme indicated that the 4 hydroxyphenylketones, similarly to ascorbate and its epimer, bound to an enzyme NADP+ binary complex as competitive inhibitors with respect to dihydrodiol substrate. The inhibition by the 4-hydroxyphenylketones was uncompetitive with respect to isoascorbate, and the addition of one of the 4-hydroxyphenylketones or isoascorbate with NADP+ afforded a great protective effect against inactivation of the enzyme by diethylpyrocarbonate or by heat treatment, which indicates that 4-hydroxyphenylketones and isoascorbate bind at the same site in or near the active center of the enzyme. The structural comparison of 4-hydroxybenzaldehyde and ascorbate suggests that the hydroxy group at C-5, carbonyl group at C-1 and lactone ring of ascorbate are important for the binding to the enzyme. PMID- 1295895 TI - Purification and characterization of monomeric isocitrate dehydrogenase with NADP(+)-specificity from Vibrio parahaemolyticus Y-4. AB - NADP(+)-dependent isocitrate dehydrogenase [IDH: EC 1.1.1.42] was purified to electrophoretic homogeneity from Vibrio parahaemolyticus Y-4, and shown to be a monomeric protein of molecular weight 80,000 with a pI of 5.0. The amino acid composition and partial sequence at the N-terminus resembled those reported for other bacterial monomeric IDHs. Immunotitration with antisera to the monomeric and dimeric enzymes (antisera to IDH-II and -I of Vibrio ABE-1) showed an immunochemical distinction between the monomeric and dimeric IDHs, but there is similarity within the IDHs of each group. The circular dichroism spectra of the native and heat-denatured enzyme are also similar to those of monomeric IDH (IDH II of Vibrio ABE-1). These monomeric IDHs are proteins comprising 17-22% helix and 25-35% beta-pleated sheet in the native state. PMID- 1295896 TI - Mechanism of human keratinocyte migration on fibronectin: unique roles of RGD site and integrins. AB - The migration of human keratinocytes over the wound bed plays an important role in the re-epithelialization of cutaneous wounds. Fibronectin, a large glycoprotein matrix component that is abundant within cutaneous wound beds, promotes keratinocyte migration. However, the mechanisms by which keratinocytes migrate over fibronectin are unknown. In this study, we sought to identify specific sites within the fibronectin molecule that induce keratinocyte locomotion and to characterize the cell surface receptors involved. The data show that the domain within the fibronectin molecule that induces human keratinocyte migration is the 120 kD cell-binding domain close to the carboxyl terminus. The 40 kD heparin-binding domain near the carboxyl terminus and the 45 kD gelatin binding domain near the amino terminus did not promote keratinocyte migration. In addition, keratinocyte migration on both fibronectin and the 120 kD cell-binding domain was completely inhibited by the presence of GRGDSP peptide, suggesting that keratinocyte migration on fibronectin is mediated by recognizing the RGD sequence located within the cell-binding domain of fibronectin. Furthermore, keratinocytes were able to migrate directly on immobilized RGD substratum. Cell migration on fibronectin is mediated by the alpha 5 beta 1 integrin since antibodies blocking the alpha 5 and the beta 1 subunits completely inhibited keratinocyte migration on fibronectin. In addition, we demonstrate that human keratinocytes express alpha 5 beta 1 integrin in culture by flow cytometry. PMID- 1295897 TI - WGA-binding, mucin glycoproteins protect the apical cell surface of mouse uterine epithelial cells. AB - Expression of apical cell surface proteins and glycoproteins was examined in polarized primary cultures of mouse uterine epithelial cells (UEC). Lectin-gold cytochemistry revealed that wheat germ agglutinin (WGA) bound specifically to the components of the apical glycocalyx as well as intracellular vesicles. Double labeling with the pH sensitive dye 3-(2,4-dinitroanilino)-3'amino-N methyldipropylamine (DAMP) demonstrated the acidic nature of the WGA-staining intracellular vesicles. The enzymatic and chemical sensitivities of the WGA binding sites on the apical cell surface were monitored both by WGA-gold staining as well as by 125I-WGA binding assays. In thin sections, a large fraction of these sites were removed by pronase; however, application of a wide variety of proteases, glycosidases, or chemical treatments to the apical surface of intact UEC failed to reduce WGA binding. In no case did treatments designed to remove sialic acids reduce 125I-WGA binding more than 12%. In contrast, endo-beta galactosidase as well as a combination of beta-galactosidase with beta hexosaminidase succeeded in removing 28% and 77% of these sites, respectively. These studies suggested that the majority of the apically disposed WGA binding sites involved N-acetylglucosamine residues rather than sialic acids and included lactosaminoglycans. Many of the proteins detected at the apical cell surface by lactoperoxidase-catalyzed radioiodination were WGA-binding glycoproteins. A major class of these glycoproteins displayed Mr > 200 kDa by SDS-PAGE and was heavily labeled metabolically by 3H-glucosamine or by vectorial labeling at the apical cell surface with galactosyl transferase and UDP-3H-galactose. Analyses of the 3H labeled oligosaccharides labeled by either procedure indicated that a large fraction of the apically disposed WGA-binding oligosaccharides consisted of neutral, O-linked mucin-type structures with median MW of approximately 1,500. Oligosaccharides in this fraction were partially (15%) sensitive to endo-beta galactosidase digestion and bound to Datura stramonium agglutinin (68%), demonstrating the presence of lactosaminoglycan sequences. UEC were an extremely effective barrier to attachment or invasion by either a highly invasive melanoma cell line, B16-BL6, or implantation-competent mouse blastocysts. In contrast, neither uterine stromal cells nor a non-polarizing UEC cell line, RL95, prevented B16-BL6 attachment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1295898 TI - Switching from differentiation to growth in hepatocytes: control by extracellular matrix. AB - Studies were carried out to analyze how different extracellular matrix (ECM) molecules regulate hepatocyte growth and differentiation. Freshly isolated rat hepatocytes were cultured on non-adhesive plastic dishes that were pre-coated with defined densities of either laminin, fibronectin, type I collagen, or type IV collagen. Sparse cell plating densities were used to minimize cell-cell contact formation and all studies were carried out in chemically defined medium that contained a saturating amount of soluble growth factors. Dishes coated with a low ECM density (1 ng/cm2) supported hepatocyte attachment, but did not promote cell spreading or growth. Computerized image analysis confirmed that over 80% of cells remained free of contact with other cells under these conditions. Yet, these round cells maintained high levels of albumin gene expression as well as elevated secretion rates for multiple liver-specific proteins (albumin, transferrin, and fibrinogen), regardless of the type of ECM molecule used for cell attachment. When ECM coating densities were raised from 1 to 1,000 ng/cm2, cell spreading, expression of histone mRNA, DNA synthesis, and cell proliferation all increased in parallel. Activation of growth by high ECM densities was also accompanied by a concomitant down-regulation of differentiated functions and again, dishes coated with all four types of ECM molecules produced similar effects. Thus, the ability to switch hepatocytes from differentiation to growth (i.e., between different genetic programs) is not limited to a single ECM molecule, a distinct three dimensional ECM geometry, or due to alteration of cell cell interactions. Rather, the regulatory signals conveyed by immobilized ECM molecules depend on the density at which they are presented and thus, on their ability to either prohibit or support cell spreading. PMID- 1295899 TI - Initial characterization of heat-induced excess nuclear proteins in HeLa cells. AB - Exposure of mammalian cells to hyperthermia is known to cause protein aggregation in the nucleus. The presence of such aggregates has been detected as the relative increase in the protein mass that is associated with nuclei isolated from heated cells. We have characterized these excess nuclear proteins from the nuclei of heated HeLa cells by two-dimensional gel electrophoresis. The abundance of cytoskeletal elements which co-purify with the nuclei did not increase with exposure to hyperthermia, indicating that these proteins are not part of the excess nuclear proteins. In contrast, several specific polypeptides become newly bound or increase in abundance in nuclei isolated from heated cells. Members of the hsp 70 family were identified as a major component of the excess nuclear proteins. Among the other excess nuclear proteins we identified ten that had apparent molecular weights of 130, 95, 75, 58, 53, 48, 46, 37, 28, and 26 kilodaltons. Since hsp 70 is mainly cytoplasmic in non-heated cells, its association with nuclei in heated cells indicates that one mechanism accounting for the heat-induced excess nuclear proteins is the movement of cytoplasmic proteins to the nucleus. We also obtained evidence that increased binding of nuclear proteins is another mechanism for this effect. No overall increase or decrease in the phosphorylation of nuclear proteins was found to be associated with such altered binding or movement from the cytoplasm to the nucleus. PMID- 1295900 TI - Mechanism of zinc uptake by microvilli isolated from human term placenta. AB - The mechanism of zinc (Zn) uptake by microvillous membrane vesicles prepared from human term placenta has been studied. The uptake was complex, with two processes being identified. In the first process, uptake was rapid, reaching equilibrium within 2 min, and was temperature dependent, with a Q10 of 1.5. Equilibrium Zn levels were sensitive to osmotic pressure, with Zn binding at infinite osmolarity being 69% iso-osmotic value. The uptake was saturable, with a Vmax of 58 +/- 2 nmol/mg protein/min and an apparent Kt of 128 +/- 13 microM. Uptake was inhibited by increasing extravesicular K+ concentration, dropping from 0.91 +/- 0.03 nmol/mg/min at 0 extravesicular K+ to 0.47 +/- 0.03 at an extravesicular K+ concentration of 150 mM ([Zn] = 1.0 microM). In the presence of both valinomycin, an electrogenic ionophore, and nigericin, an electroneutral exchanger, an outwardly directed K+ gradient stimulated Zn uptake. Similarly, preloading vesicles with Zn and imposing an inward gradient resulted in a temperature dependent efflux of Zn. The data suggest that there is a K+ dependent Zn transporter in vesicle membranes, and we suggest that the evidence is biased in favour of a Zn/K+ exchanger rather than Zn being dependent on the membrane potential. PMID- 1295901 TI - Inhibition by 1,25 dihydroxyvitamin D3 of c-myc down-regulation and DNA fragmentation in cytosine arabinoside-induced erythroid differentiation of K562 cells. AB - The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on DNA fragmentation, altered expression of the heat shock protein (hsp) 70 gene, and protooncogenes c myc and c-myb was studied during chemical induction of erythroid differentiation in K562 cells. Preincubation of K562 cells with 1,25(OH)2D3 did not alter the concentration of hemoglobin in cells which did differentiate, but led to a reduction in the accumulation of low molecular weight DNA generated by Ara-C administration. The extent of this reduction was similar to the degree of inhibition of hemoglobin formation in the culture as the whole. Preincubation with 1,25(OH)2D3 had no effect on the increase of hsp 70 gene expression induced by a 48-hr treatment with Ara-C, but prevented the Ara-C-induced down-regulation of the protooncogene c-myc. The protooncogene c-myb was down-regulated after 15 min of treatment with Ara-C, and exposure to 1,25(OH)2D3 prior to Ara-C caused a further down-regulation of its expression. The data suggest that the events associated with erythroid differentiation may be separable into at least two groups; one of these may have an influence on the kinetics of the cell cycle traverse, and the other may be related to the expression of the erythroid phenotype. PMID- 1295902 TI - Stimulation of endothelial cell proliferation by vanadate is specific for microvascular endothelial cells. AB - Micromolar concentrations of sodium orthovanadate stimulated the proliferation of bovine capillary endothelial cells, but not bovine aortic endothelial cells. Vanadate was equally potent at inducing protein tyrosine phosphorylation and changes in morphology in both types of cells. However, vanadate treatment lead to an inhibition of protein tyrosine kinase activity in the aortic endothelial cells, but not the capillary endothelial cells. In capillary endothelial cells, the effect of vanadate was additive with basic FGF (bFGF) at low concentrations of bFGF. There was no interaction between bFGF and vanadate in aortic endothelial cells. TGF-beta, which inhibits the induction of endothelial cell proliferation by bFGF, appeared to shift the dose response curve to vanadate in capillary endothelial cells, increasing the proliferative effect of vanadate at low vanadate concentrations, but decreasing the proliferative effect at higher vanadate concentrations. PMID- 1295903 TI - Induced thermotolerance to apoptosis in a human T lymphocyte cell line. AB - A brief exposure to elevated temperatures elicits, in all organisms, a transient state of increased heat resistance known as thermotolerance. The mechanism for this thermotolerant state is unknown primarily because it is not clear how mild hyperthermia leads to cell death. The realization that cell death can occur through an active process of self destruction, known as apoptosis, led us to consider whether thermotolerance provides protection against this mode of cell death. Apoptosis is a common and essential form of cell death that occurs under both physiological and pathological conditions. This mode of cell death requires the active participation of the dying cell and in this way differs mechanistically from the alternative mode of cell death, necrosis. Here we show that mild hyperthermia induces apoptosis in a human leukemic T cell line. This is evidenced by chromatin condensation, nuclear fragmentation and the cleavage of DNA into oligonucleosome size units. DNA fragmentation is a biochemical hallmark of apoptosis and requires the activation of an endogenous endonuclease. The extent of DNA fragmentation was proportional to the severity of heat stress for cells heated at 43 degrees C from 30 to 90 minutes. A brief conditioning heat treatment induced a resistance to apoptosis. This was evident as a resistance to DNA fragmentation and a reduction in the number of apoptotic cells after a heat challenge. Resistance to DNA fragmentation developed during a recovery period at 37 degrees C and was correlated with enhanced heat shock protein (hsp) synthesis. This heat-induced resistance to apoptosis suggests that thermotolerant cells have gained the capacity to prevent the onset of this pathway of self-destruction. An examination of this process in heated cells should provide new insights into the molecular basis of cellular thermotolerance. PMID- 1295904 TI - Fibroblast growth factor upregulates PGG/H synthase in rabbit microvascular endothelial cells by a glucocorticoid independent mechanism. AB - The present study was undertaken to determine the effects of acidic fibroblast growth factor (aFGF) on eicosanoid synthesis in microvessel endothelial cells derived from rabbit left ventricular muscle (RCME cells). We observed that aFGF increased AA conversion to PGE2 in a time- and dose-dependent manner, and the stimulatory effect was abolished by actinomycin D and cycloheximide. Acidic FGF increased the recovery of PGG/H synthase activity following aspirin treatment, suggesting an action on de novo PGG/H synthase synthesis. Acidic FGF increased the incorporation of [35S] methionine into a 70 kD immunoreactive PGG/H synthase band. PGG/H synthase synthesis following aspirin treatment was also increased by transforming growth factor beta, while epidermal growth factor basic FGF and platelet derived growth factor were without effect. In addition, the actions of aFGF on de novo PGG/H synthase were compared in several endothelial preparations. Acidic FGF treatment of aspirin treated endothelial cells from rabbit lung microvessels and small pulmonary artery and from human lung microvessels all showed an increase in PGG/H synthase recovery. In contrast, similar treatment of human umbilical vein endothelial cells was without effect. Pretreatment of RCME cells with dexamethasone (1 microM) did not alter the aFGF induction of PGG/H synthase activity. We conclude that aFGF stimulates PGE2 production by a mechanism that includes the de novo synthesis of PGG/H synthase. This mechanism appears to be distinct from previously described glucocorticoid sensitive translational controls of PG synthase synthesis by epidermal growth factor in smooth muscle and mesangial cells. PMID- 1295905 TI - 1,25-Dihydroxy-vitamin-D3 enhances antiproliferative effect and transcription of TGF-beta1 on human keratinocytes in culture. AB - Both TGF-beta and 1,25-dihydroxy-vitamin-D3 (1,25(OH)2D3) have been reported to decrease the proliferation of normal human keratinocytes. The effect and expression of TGF-beta in keratinocytes treated with 1,25(OH)2D3 was investigated. Human keratinocytes were grown in the presence of various concentrations of TGF-beta and/or 1,25(OH)2D3 prior to enumeration. TGF-beta, alone, has a half maximal dose of inhibition (ED50) of approximately 750 pg/ml after seven days in culture in Keratinocyte Growth Medium (KGM; Clonetics) supplemented with 1.5 mM calcium. When 1,25(OH)2D3 (10(-7)M) was also added to cultures with various concentrations of TGF-beta, the ED50 shifted an average of 2-fold less. The presence of TGF-beta (10 pg/ml) augmented the potency of 1,25(OH)2D3 by at least 10-fold. In keratinocyte cultures, the antiproliferative effect of the two compounds together is synergistic. In keratinocytes grown for 1 week in the presence of 1,25(OH)2D3 at 10(-6)M, the TGF-beta 1 message increased approximately 5-fold. An increase is detected within 2 hours of exposure to 1,25(OH)2D3. There was only a 50% increase in the levels of TGF-beta 2 and no detection of TGF-beta 3. When keratinocyte cultures were treated with 1,25(OH)2D3 and neutralizing antibodies to TGF-beta, the induced-antiproliferative activity was blocked by more than 50%. The keratinocytes produced more active than latent TGF-beta after growth with high doses of 1,25(OH)2D3. PMID- 1295906 TI - Regulation of vascular smooth muscle cell integrin expression by transforming growth factor beta1 and by platelet-derived growth factor-BB. AB - We have examined the ability of transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor-BB (PDGF-BB) to regulate the expression of various integrins in cultured rabbit vascular smooth muscle cells (SMC). We found that expression of the alpha v beta 3 integrin complex was induced by both growth factors, although TGF-beta 1 appeared to be the more potent inducer. mRNA level of the beta 3 integrin subunit was undetectable in quiescent cells and enhanced by both growth factors, while the alpha v integrin subunit mRNA level did not change with growth factor addition. Therefore, appearance of the alpha v beta 3 integrin protein complex after growth factor stimulation was due to increased expression of the beta 3 integrin subunit mRNA. The TGF-beta 1 induced increase in beta 3 integrin mRNA was delayed, but did not require prior protein synthesis, since cycloheximide was unable to block the increase in beta 3 mRNA level. By contrast, PDGF-BB induced a more rapid increase in beta 3 integrin mRNA level that peaked by 6 h after growth factor addition and no detectable beta 3 integrin mRNA remained after 24 h. Interestingly, the PDGF-BB induced elevation of beta 3 integrin, although more rapid, was completely inhibited by cycloheximide. Expression of the alpha 5 integrin subunit in response to growth factors was very similar to beta 3. However, in contrast to beta 3 and alpha 5, neither TGF-beta 1 nor PDGF-BB were able to alter the expression of the beta 1 integrin subunit in vascular SMC. However, in TGF-beta 1 treated cells, there was a large increase in expression of a 190 kDa polypeptide that was associated with the beta 1 integrin subunit. This 190 kDa polypeptide was not detected in PDGF treated SMC or in TGF beta 1 treated fibroblasts. The alpha 1 integrin subunit has a MW of approximately 190 kDa and is capable of complexing with beta 1. Analysis of the alpha 1 integrin subunit mRNA level indicated that it was indeed induced by TGF beta 1, but not by PDGF-BB, suggesting that the 190 kDa polypeptide may be the alpha 1 integrin subunit. These results indicate that TGF-beta 1 and PDGF-BB are potent but distinct activators of integrin expression in vascular SMC. PMID- 1295907 TI - Quick and accurate method to convert BCECF fluorescence to pHi: calibration in three different types of cell preparations. AB - A rapid, easy, and accurate method for converting the fluorescence of BCECF to pH, as an alternative to the nigericin method, is described. The ratio of the fluorescence intensities for BCECF can be converted to pH between 4 and 9 by a formula similar to the one used to calculate [Ca2+]i from the fluorescence of fura2. The formula is inverted because H+ binding to BCECF causes a decrease in fluorescence, whereas Ca2+ binding to fura2 causes an increase in fluorescence. The ratio of the fluorescence intensities is a sigmoidal function of the [H+] between pH 4 and 9 with an essentially linear mid region from pH 6 to 8. This calibration procedure in cells is similar to the popular method for fura2 where ionomycin, Ca2+, and an alkaline EGTA solution are added in succession to change the intracellular pCa from 4 to 9. For BCECF in cells, a protonophore, FCCP or CCCP, is added and the cells are titrated with acid to an intracellular pH of 4 and then back to pH 9 with base by observing the gradual change in fluorescence as it asymptotically reaches its limiting minimum and maximum values. This method does not require changing the medium to one with high KCl to depolarize the membrane potential nor does the proton concentration need to be equilibrated across the plasma membrane. The technique can be used to calibrate BCECF in sheets of cells, as well as suspensions of cells over a wide range of pH sensitivities. PMID- 1295908 TI - [Celioscopic digestive surgery]. PMID- 1295909 TI - [Safety of cholecystectomy by laparotomy in elective situation and in emergency]. AB - Cholecystectomy is the only effective treatment of gallbladder stones. A retrospective study was carried out on results of 658 cholecystectomies by laparotomy without choledochotomy performed between January 1987 and December 1989, to determine morbidity and mortality of elective and emergency surgery and by age. Operations for tumors of the gallbladder and choledolithiasis were not included in the analysis. During this period, cholecystectomy was performed electively in 387 cases and under emergency conditions in 261 patients. Mortality and post-operative morbidity were 0% and 14.7% respectively after elective surgery, increasing to 1.1% (Fisher = 0.0617) and 25.2 (p = 0.0004) respectively after emergency operations. This large increase in postoperative morbidity in urgent cases was due to an increase in systemic and not local complications, as a result of the higher proportion of emergency operations with advancing age. Since elective cholecystectomy is safe it can be proposed to patients with symptoms, including the elderly. It is difficult at present to compare results of cholecystectomy by laparotomy with those of laparoscopy since the average age of in the latter category is markedly lower and the number of acute cases still low. The principal advantage of celioscopy could be a long term reduction in systemic complications in emergency operations. PMID- 1295910 TI - [Prognostic factors of femoropopliteal shunts. Retrospective study of a series of 52 shunts]. AB - Between January 1986 and January 1991, 52 femoropopliteal shunts were carried out in 51 patients for lesions defined by the Ad Hoc Committee as grade III in 36 cases, grade II in 10 and grade I in 6. The shunt graft used was the internal saphenous vein in situ in 34 cases, inversed in 13 cases, and a PTFE prosthesis in 5 cases. The postoperative course included 12 complications and one death. At the end of the study, 10 shunts had thrombosed and 4 patients had required a major amputation. Actuarial analysis at 5 year follow up showed primary permeability of 56% and secondary permeability of 60%. Statistical analysis of secondary permeability as a function of the distal bed, an associated diabetes or the in situ or inversed venous shunt, failed to demonstrate any significant difference. These femoropopliteal venous shunts in critical ischemias reduced the incidence of major amputations, the proportion of limbs saved being higher than that for shunt permeability from the 6th postoperative month. Poor results were recorded for femoropopliteal shunts using prostheses. PMID- 1295911 TI - [Peritonitis after spontaneous rupture of a pyonephrosis into the peritoneal cavity. Apropos of a case]. AB - Peritonitis by fistulization of a pyonephrosis is an extremely rare complication usually diagnosed perioperatively. Treatment is by immediate or deferred nephrectomy after ensuring the functional condition of the contralateral kidney. PMID- 1295912 TI - [Surgery called tumoral reduction: myth or reality?]. AB - The cytoreductive surgery (CS) or surgical debulking of tumors is supported by the following experimental concept: the maximal but incomplete resection of huge tumoral masses (debulking) induces the passage of remaining cancerous cells in proliferative cycle. So, these remaining cells become sensitive to chemotherapy, or eventually to radiotherapy. In this way, the CS appears to be a neoadjuvant treatment to the chemotherapy, this last treatment being the powerful therapeutic. In this study, we have studied successively: the theoretical basis of the CS, the experimental positive and negative arguments of this concept, and then the positive and negative clinical applications. At least, it seems that CS is more a myth than a reality, and that we should only keep the classical concepts of curative surgery or palliative surgery. PMID- 1295913 TI - [Treatment of extrahepatic bile duct calculi in 1992. Strategy and tactics]. PMID- 1295914 TI - [Laparoscopic cholecystectomy: technical gestures]. PMID- 1295915 TI - [Evaluation of celioscopy in the emergency treatment of acute cholecystitis]. PMID- 1295916 TI - [The "wall-hanger" and celio-surgery]. PMID- 1295917 TI - [Intraoperative cholangiography in cholecystectomies under laparoscopy]. PMID- 1295918 TI - [Place of biliary ultrasound endoscopy in the surgical treatment of cholelithiasis]. PMID- 1295919 TI - [Endoscopic sphincterotomy and cholecystectomy under celioscopy]. PMID- 1295921 TI - [Confrontation anesthetists-surgeons in cholecystectomy under celioscopy. "Duel or Duo"]. PMID- 1295920 TI - [Common bile duct calculi and celiosurgery]. PMID- 1295922 TI - [Complications of cholecystectomies under endoscopy. Apropos of 6512 cases]. PMID- 1295923 TI - [Responsibility and therapeutic choice for extrahepatic cholelithiasis]. PMID- 1295924 TI - [Treatment of cholelithiasis. Conclusion]. PMID- 1295925 TI - [Plication of the common femoral artery, a differential diagnosis with endofibrosis of the external iliac artery in racing cyclists]. PMID- 1295926 TI - [Gastric leiomyoma. Apropos of two cases and review of the literature]. PMID- 1295927 TI - Diagnostic model for local temporal thermal change at the skin of the breast during extended application of diagnostic ultrasound. AB - A biophysical model is derived to account for the temporal thermal change at the skin of the breast as a result of ultrasound stimulation at the suspect lesion for seven minutes, with responses recorded using an infrared camera. Twenty-two patients were studied. The observed temporal responses for malignant cases have a different pattern from those of the benign cases studied and a mathematical model is used to investigate the controlling parameters. A new method is used to estimate the coefficients of the resulting difference equation which allows more useful diagnostic parameters to be computed than the corresponding continuous bioheat equation. The model is used to fit the experimental data. The results suggest that this method might be a rapid and noninvasive aid for distinguishing between benign and malignant breast tumours. PMID- 1295928 TI - Mathematical models of wound healing in embryonic and adult epidermis. AB - Epidermal wound healing occurs by quite different mechanisms in embryos and adults. In the latter case, it has long been known that cells crawl inwards via lamellipodia to close the defect. In the embryonic system, recent evidence suggests that healing may be caused by a quite different mechanism, namely the contraction of a cable of filamentous actin at the wound edge. The authors use mathematical modelling to investigate both systems. A mechanical model for the initial formation of the actin cable in embryonic epidermal wounds is presented, which incorporates the important phenomenon of stress-induced microfilament alignment. Also discussed is a reaction-diffusion model for the healing of adult wounds subject to autoregulation of cell division. In both cases, the results suggest possible biological mechanisms for key aspects of the healing process. PMID- 1295929 TI - Optimal chemical control of populations developing drug resistance. AB - A system of differential equations for the control of the growth of certain populations by the use of chemical treatment is presented. Rather general growth rates and kill rates of drugs, as well as drug resistance, are considered. A class of optimal control problems with a performance criterion depending on a parameter is formulated and shown to admit the same basic optimal strategy. Applications to cycle nonspecific chemotherapy and control of the growth of bacterial populations in cellulose media in paper production plants are described. PMID- 1295930 TI - Quantitative analysis of platelet function using stagnation point flow aggregometry. First clinical results. AB - BACKGROUND: The clinical consequences of atherosclerosis result from vascular occlusion. The central role of platelet-vessel wall interaction in the initiation and perpetuation of this process is well established. Individual analysis and quantification of two major platelet functions underlying atherosclerosis and thrombosis, i.e. adhesion (platelet-wall interaction) and aggregation (platelet platelet interaction), would contribute significantly towards elucidation of the mechanisms involved and therefore towards optimization of prophylaxis and therapy. The Stagnation-Point-Flow-Adhesio-Aggregometer (SPAA), in which such an evaluation of platelet function is possible, was thus standardized and its clinical reproducibility and predictive power assessed. METHODS: Using the SPAA, a morphometric separation of adhesion and aggregation is obtained via dark field micrographs of platelet microthrombi formed during stagnation point flow of platelet rich plasma (PRP). Quantification is achieved via biomathematical evaluation of simultaneously obtained growth curves, whereby the degree of adhesivity and aggregability is reflected in the respective growth rate constants Kpw (%) and Kpp (%). Experiments with the PRP of 36 healthy volunteers were performed and the results compared to those obtained for 32 patients exhibiting angiographically verified peripheral arterial disease (PAD). RESULTS: The control group exhibited values (Kpw) ranging from 0.40% to 1.10% (average Kpw: 0.71 +/- 0.21%). Differences in average Kpw value between the control subgroup over and that under 45 years of age were absent. A spontaneous platelet aggregation was not observed in the controls (Kpp = 0%). The overall intraindividual Kpw variation in 18 volunteers examined 3 times or more ranged from a minimum of 3% to a maximum of 20% of respective Kpw value. The patients were divided into two subgroups: diabetics and nondiabetics. The nondiabetic group demonstrated an average Kpw of 1.56%. In addition, a spontaneous aggregation was observed in 50% of all experiments (average Kpp = 1.42%). The diabetic group exhibited the highest average adhesion value (Kpw = 1.94%) occurrence of spontaneous aggregation in all experiments (Kpp = 2.10%). CONCLUSION: The consistency in adhesion values obtained among the controls as well as the minimal intraindividual variance observed, demonstrates the reproducibility of the method. The statistically significant increase (p < 0.001) in adhesivity of patients as compared to controls, as well as the common occurrence of spontaneous aggregation can therefore be considered a pathologic platelet response reflecting the severity of the disease. Results obtained verify the presence of circulating hyperreactive platelets in PAD patient and indicate the predictive power of the method. Thus the SPAA may be of considerable aid in improving thrombosis prophylaxis and therapy. PMID- 1295931 TI - A monkey model for mucoid vasculopathy. AB - Mucoid vasculopathy is a new vascular entity observed by the Author in autopsy material in Kerala, a southwest coastal state of tropical India. This non atherosclerotic, non-inflammatory connective tissue disorder affects mainly arteries, veins, vasa-nervosum and fascial tissues. Characteristically, there are large deposits of acid mucopolysaccharide (glycosaminoglycan) material in the intima and media of arteries, accompanied by hyperplastic changes in cellular elements of the vessel wall and dystrophic changes in internal elastic laminae. There is secondary mineralization of elastic laminae and of medial mucoid material in some cases. To ascertain the role of diet in the aetiology of mucoid vasculopathy, groups of bonnet monkeys were fed protein-deficient normal carbohydrate, or protein-deficient high-carbohydrate tapioca (cassava) starch based diets or control diets of normal protein and carbohydrate for 3 or 5 months periods. The diet of the poorer sections in Kerala is deficient in protein and tapioca is the main source of carbohydrate. A generalised mucopolysaccharidosis and vasculopathy similar to the human condition and associated with some cardiomyopathic changes could be induced in the monkeys by protein deficient diets. These were enhanced both by ingestion of a high carbohydrate and by a longer experimental period. In order to exclude the effect of toxic factors which might be present in tapioca starch, experiments were repeated with corn starch as the carbohydrate: identical cardiovascular lesions were induced. The animal experiments established pivotal role for protein-deficiency in inducing mucoid vasculopathy with enhancement of degenerative cardiovascular lesions by ingestion of higher levels of carbohydrate in a protein-deficient state. This experimental study establishes a good animal model for mucoid vasculopathy. PMID- 1295932 TI - Reduced thrombogenicity of vascular prostheses by coating with ADP-ase. AB - In this pilot study ADP-ase coated polyurethane (PU) vascular prostheses and noncoated (control) PU vascular prostheses (all vascular prostheses: ID 1.5 mm, length 1.5 cm) were implanted into the carotid artery of the rabbit to test whether ADP-ase might function as an adequate anti-thrombogenic coating. The prostheses were evaluated after 1 hour (n = 4) and 3 weeks (n = 8). After 1 hour, there was extensive accumulation of thrombus on the inner surface of the control PU vascular prostheses, in contrast to the ADP-ase coated prostheses. At 3 weeks, all control PU vascular prostheses (n = 8) were occluded, whereas only 1 of the 8 ADP-ase coated PU vascular prostheses. The patient ADP-ase coated PU prostheses showed already extensive endothelial healing. These results indicate the potential of ADP-ase to function as an effective antithrombogenic coating of small-caliber and microvascular PU prostheses. PMID- 1295933 TI - Medical writing: inadvertent humor and other anomalies. AB - Although most readers consider medical publications to be somber and somnifacient, a critical eye will discover a remarkable array of absurdities and assorted other oddities, totally unintended by the authors. These eccentricities can be attributed to failure of the author to engage the mind before activating the pen, a lapse of attention during preparation of the manuscript, or an effort to convey profundity and conceal vacuity by inflated and pompous language. The egregious examples from prestigious journals included here should alert medical authors that eternal vigilance to clear, orderly reasoning and lucid, orderly language is crucial during preparation of a manuscript. To acquire a pleasing and distinctive literary style, read extensively of the literary masters, approach writing with enthusiasm for its challenges and rewards, experiment with the choice and arrangement of words and phrases, and read critically every word, phrase, sentence, paragraph, and section of your manuscript as though you were your most critical adversary. PMID- 1295934 TI - Failure of selective shunting to intercostal arteries to prevent spinal cord ischemia during experimental thoracoabdominal aortic occlusion. AB - Paraplegia from spinal cord ischemia during thoracoabdominal aneurysm repair remains an unpredictable and unpreventable complication. In an effort to prevent spinal cord ischemia during aortic cross-clamping, preoperative angiographic localization of the blood supply to the spinal cord was performed in dogs. Sixteen animals underwent 60 minutes of thoracoabdominal aortic cross-clamping either without (control, n = 8) or with (shunted, n = 8) a selective shunt. Shunting was performed from the aortic arch to that isolated aortic segment angiographically shown to supply the thoracolumbar anterior spinal artery. Spinal cord blood flow was measured with microspheres just prior to cross-clamping, at 5 and 60 minutes after cross-clamping and at 5 minutes after restoration of aortic blood flow. Functional neurologic outcome was evaluated in animals at 24 hours postoperatively. Shunting did not decrease spinal cord injury. Seven of the 8 animals in the control group and 7 of the 8 in the shunted group developed paraplegia or paraparesis. Thoracic, but not lumbar spinal cord blood flow, was significantly increased in shunted animals. Spinal cord blood supply in dogs may be more segmental than previously believed. Technical problems in angiographic localization, spinal artery spasm, loss of spinal cord autoregulation or poor collateral circulation from the distal thoracic to the lumbar cord may also account for these results. Although shunting to aortic segments supplying the anterior spinal artery during thoracoabdominal aortic clamping may be attractive in humans, no benefit could be shown in this experimental model. PMID- 1295935 TI - Ankle and toe systolic pressures comparison of value and limitations in arterial occlusive disease. AB - Ankle and toe systolic pressures represent the most convenient and useful measurements in the assessment of limbs with arterial occlusive disease. Each is a sensitive index of the presence and severity of the arterial obstruction and they both correlate with angiographic findings and with the severity of the symptoms. The measurements can be used to follow individual patients, to study the natural history of the disease, to assess prognosis and plan management, and to evaluate long-term results of surgical and transcutaneous interventions. However, because of the limitations of the ankle pressures related to the rigidity of the arterial walls of the tibial vessels and the more distal site of the measurement in the toes, measurements of pressure in the toes should be included in the evaluation of arterial disease in all patients with diabetes, and in all limbs with severe ischemia. PMID- 1295936 TI - Experimental venous thrombosis: what animal model? AB - A new experimental venous thrombosis model is described and its role relative to other models is defined. Previous models are not satisfactory for all types of investigation. Opposite, present model based on the three classic thrombogenic factors is suitable for venous scintigraphy and evaluation of different forms of therapy for venous thrombosis of the limbs. So this model permits research on diagnosis and therapy of thromboembolic disease. PMID- 1295937 TI - Raynaud's phenomenon: subjective influence of female sex hormones. AB - Recent studies with standardized laboratory measurements of skin blood flow suggest an influence of female sex hormones on vasospasm. Therefore we evaluated the influence of sex hormonal status on the subjective complaints of Raynaud's phenomenon and furthermore the combined presence of Raynaud's phenomenon and migraine. A detailed questionnaire was filled in by 130 primary Raynaud patients (31 males, 99 females), while 27 females, with regular menstrual cycles without the use of oral contraceptives, kept a diary with daily registration (during three months) of frequency, severity and duration of the vasospastic attacks. Complaints improved during pregnancy in 6 out of 23 females. No influence of the menopause or the use of oral contraceptives was found. An exacerbation in some phases of the menstrual cycle was present in 15 out of 80 females. The diaries, however, did not show such influence of menstrual cycle phase. Migraine was present in 21% of the Raynaud patients. In contrast to most reports in the literature and contrary to the results of laboratory research, this study shows that most females do not experience an important subjective influence of sex hormonal status on vasospastic attacks. PMID- 1295938 TI - Cutaneous circulation in Raynaud's phenomenon during emotional stress. A morphological and functional study using capillaroscopy and laser-Doppler. AB - In order to assess the effects of emotional stress on the cutaneous microcirculation in patients suffering from Raynaud's phenomenon (RP) a group of 18 patients with this pathology and 16 healthy control subjects underwent an "arithmetical test". The microcirculatory response was examined using a laser Doppler apparatus. The results obtained showed a constantly reduced flow during mental stress in normal subjects; in the RP group it was possible to observe: a first subgroup with a reduced flow similar to that seen in normal subjects, and a second subgroup with a paradoxically increased flow. It is likely that the normal vasoconstrictor response is the expression of the functional impairment of the microcirculation alone (primary RP), whereas vasodilatation in response to mental stress is a sign, of the organic development of the disease right from an early stage. PMID- 1295939 TI - Child abuse as an inhibiting factor for family planning. AB - The aim of this study is to determine the magnitude of the problem of using children as an economic asset to the family thus, in one way increasing the prevalence of child abuse in Egypt and also hindering the family planning program. Two focus-group interviews were conducted in urban & rural areas for 10 women with the same age range and socioeconomic background. All were non-users of any contraception. Subsequently an interview was conducted for all women who attended the Ob. & Gyn. Clinic at Ain Shams University Hospital in the period from June to August 1991, their ages ranged from 30-35 years and they never used contraception. Another group of women with the same characteristics were interviewed from a rural area at Fayoum Governorate. A questionnaire was filled for each interviewed woman. The total women interviewed in urban area is 340 while in the rural area they were 400 women. Sixty percent of urban women and 80% of rural women are illiterate, 70% of the urban & 100% of rural women are housewives. Their years of marriage ranged between 10-20 years and all of them have more than five children. A percentage of 73.5% of urban women and 85% of rural women stated that children are used as an economic asset to their families, they work in urban areas as assistants in motor repairs, hair-dressers, beggars, bakeries, shops, restaurants and factories while in rural areas they work as agricultural workers. PMID- 1295940 TI - Epidemiologic study of premenstrual symptoms. AB - The frequency of selected premenstrual symptoms among 342 Egyptian women were analyzed in relation to demographic and reproductive characteristics. The frequency ranged from 36% for breast pain or tenderness to 66% for premenstrual stomach and back cramps, socioeconomic status, education, age at menarche, breast size, menstrual irregularity, and history of pregnancy are all associated with the premenstrual symptoms. PMID- 1295941 TI - Dietary patterns and nutritional assessment of working children at Abou El-Dardar industrial area in Alexandria City. AB - The present study was undertaken in order to evaluate the nutritional status of young working children aged 8 to 18 years, working in workshops at Abou-El-Dardar industrial area in Alexandria Governorate. A total sample of 154 of young male workers were recruited from workshops. The nutritional status was assessed using anthropometric, dietary and biochemical criteria. The results of the study revealed that 45% of the working children were considered malnourished: 16% were wasted, 23% were stunted and 3% were both wasted and stunted and 3% were overweight. Analysis of nutrient intake revealed that the intakes were less than the recommended for energy, calcium, vitamin A, vitamin C and niacin, while the intake of protein, iron, thiamin and riboflavin were more than sufficient. About 77% of the young workers were found to have haemoglobin levels below the cut-off levels issued by WHO. A high prevalence of parasitic infection (food-borne) (72%) was found among young workers. The results also revealed that stunting, wasting and stunting together and overweight were more common in young workers who were both anaemic and had evidence of parasitic infection than those who were anaemic only or had parasitic infection only. PMID- 1295942 TI - Campylobacter jejuni in acute diarrhoea in infancy and its relation to faecal leucocytic count. AB - A prospective study was carried out to identify the relative risk of Campylobacter jejuni infection in 50 infants with acute diarrhoea, 24 infants with acute resistant diarrhoea and 25 healthy normal infants as a matching control group. Faecal samples were collected from the three groups and were cultured on both selective media for Campylobacter and other media for isolation of other organisms. Direct stool smears, stained with methylene blue, were examined for detection of faecal leucocyte in all samples. Campylobacter jejuni were isolated from 4 cases (8.0%) of the acute diarrhoeal group and 4 cases (16.6%) of acute resistant diarrhoeal group. The other bacterial pathogens isolated from our cases were Salmonella, Shigella, E. Coli, Proteus mirabilis, Vibrio Parahaemolytious Klebsiella, Streptococcus faecalis and Candida albicans. All cases from whom Campylobacter was isolated were bottle fed and their ages were below 6 months. Smears for faecal leucocytes were positive in 100% of Campylobacter isolated cases, 60% of Salmonella, 50% of Shigella, 14% of E. Coli and 100% were negative in all other cases. Thus it can be recommended that any case presenting with acute diarrhoea should be initially screened by faecal leucocytic counting, positive cases should be cultured for Campylobacter jejuni detection in addition to cultures for other organisms detection. PMID- 1295943 TI - Delta virus infection in Egypt. AB - The present study was carried out on 124 serum samples of acute hepatitis B, 51 with chronic HBV infection, and 41 chronic HBsAg carriers. Sera were tested by ELISA for HBV markers and anti-delta (anti-HDV). Delta infection (anti-HDV) in acute HB was found to be 16.9% (21 out of 124), 23.5% in chronic HB cases (12 out of 51), and 21.9% among chronic HBsAg carriers (9 out of 41). Out of the twelve delta positive in chronic HB patients, ten (83%) were suffering from CAH (chronic active hepatitis) denoting a possible role of delta infection in deteriorating the course of the disease. A competitive inhibition of HBV replication by coexistent delta infection was demonstrated in the present study. This was reflected on anti-HBc IgM in the acute cases and on HBeAg in chronic HB cases. Anti-HBc IgM was 71.42% (15 out of 21) in delta positive acute HB patients versus 92.23% (95 out of 103) in delta negative acute HB patients. On the other hand, HBeAg percentage was 8.33% (1 out of 12) and 46.15% (18 out of 39) in delta and non-delta chronic HB patients respectively. The difference in both anti-HBc IgM and HBeAg as regards delta positive and negative patients was found to be statistically significant. Out of the twelve chronic HB cases with delta infection, four cases were negative for HBsAg (33.33%). This observation might be attributed to the clearance effect of hepatitis D virus (HDV) on HBsAg (Ischimura et al., 1988) or due to suppressing effect resulting in low undetectable HBsAg level in serum, (Sherlock, 1989). From the present study it may be concluded that delta infection is endemic in Egypt (its incidence ranged from 16.94% in acute HB to 23.53% in chronic HB infection), delta infection possibly also worsens the outcome of chronic HB patients. Delta infection may exert a competitive inhibitory effect on HBV replication. PMID- 1295944 TI - Non-A, non-B viral hepatitis in Egypt. AB - A study was carried out on 200 patients of ages 20-40 years suffering from acute viral hepatitis. Sera were tested for markers of hepatitis B (HBsAg, and IgM anti HBc) and hepatitis A (IgM-anti-HAV) by the ELISA technique. Sera negative for the markers of both viruses: Hepatitis A (HAV) and Hepatitis B (HBV) were subsequently tested for IGM Heterophil antibodies against Epstein-Barr virus (EBV) by the Monospot slide test to diagnose acute infectious mononucleosis and tested for anti-CMV (IgM) by ELISA technique for the diagnosis of acute Cytomegalovirus (CMV) infection. Non-A, non-B hepatitis (NANB) was diagnosed by exclusion. The results of the study showed that 133 (66.5%) patients had evidence of HBV infection, while only 9(4.5%) were diagnosed as HAV infection. EBV and CMV were the possible etiological agents of acute viral hepatitis in (3.5%) and 1%) respectively. Accordingly the Non-A, non-B hepatitis in this study amounts to (24.5%) of the acute viral hepatitis. PMID- 1295945 TI - Evidence of a 1985-1987 outbreak of acute and chronic hepatitis in Egypt caused by a mutant hepatitis-B virus detected by spot-DNA hybridization test. AB - Sera from 65 acute and 113 chronic sporadic hepatitis were screened for serological markers of hepatitis-B virus (HBV) and hepatitis delta virus (HDV) and for HBV-DNA. The enzyme linked immune sorbent assay (ELISA) and dot-DNA hybridization tests were used. Two HBV-DNA probes and their labelling systems (biotin, radiolabelling with 32P and digoxigenin) were compared for sensitivity and specificity. The 65 acute sera had serological parameters of HBV infection in 38 (58%) when all these sera were HBsAg, IgM anti HBcAg positive plus HBeAg presence in 11/38 sera. Some of the acute sera had markers of acute HBV and HDV coinfection in 14 and superinfection in 13. Thus HBV with HDV represented 27 (41.5%) of the acute hepatitis in this study. Correlation of these serological markers with dot-DNA hybridization results showed that serum HBV-DNA was present in 36/38 (94.7%) of the acute HBV infection. In the case of acute HBV+HDV positive antigenemia 4/6 had serum HBV-DNA while 10/21 of acute HBV with anti deltaV. IgM had serum HBV-DNA. There were four cases that gave HBV-DNA positivity in sera without combination of HBV markers suggesting infection with "mutant" HBV. In the chronic hepatitis sera there were markers of HBV past infection (IgG anti HBc in 63/113 and IgG anti HBs in 36/113). Yet, among these sera there was HBV-DNA positive signals (20/63 and 17/36) respectively. Analysis of some of these HBV markers also suggested infection with "mutant" HBV. PMID- 1295946 TI - Bordetella pertussis FHA antibodies in maternal/infants sera and colostrum. AB - The high incidence of pertussis in the first year of life confirms that susceptibility remains high for children in this age group despite > 90% pertussis vaccine compliance. In this respect, immunoresponse to Bordetella pertussis was investigated. Filamentous hemagglutinin (FHA) antibodies were studied due to their important protective role, in blocking the adherence of the bacteria to respiratory tract ciliated cells. The relative rate of detection and degree of positivity of IgG and IgA antibodies to Bordetella pertussis FHA were studied in maternal and infant sera and in colostrum samples of the respective mothers. The study comprised 143 mothers of child bearing age and 25 newborns. The highest percentages of serum IgG and IgA were present in the younger females group (15-25 yrs). Both IgG and IgA were detected in the same mother in 60% of them. The study showed that 96.9% of colostrum samples who were positive for IgA, were associated with IgA positivity in serum, also an increase in the degree of serum IgA positivity was associated with a higher rate of detection of IgA in colostrum. Maternal serum IgA could therefore be used as a marker for the future presence of IgA in colostrum. This work demonstrated that newborns show little passive immunity to pertussis, evidenced by the low placental transfer of IgG (35.7%) and the low rate of detection of IgA in the colostrum (41%). We concluded that, it would be advantageous to reimmunize pregnant women, without adequate serum antibody to Bordetella pertussis, with appropriate new vaccine which would offer a better passive immunity to their infants. PMID- 1295947 TI - A genetic study of vitamin D deficiency rickets: 2-sex differences and ABO typing. AB - In a further attempt to study the role of genetics in vitamin D deficiency rickets, 400 rachitic infants randomly chosen and aged from 6 months to 2 years (14.3 +/- 3.5 months) were investigated for sex differences and ABO typing. A significant (P < 0.001) predominance of the male sex was found, sex ratio being 1.43. Blood group A was significantly (P < 0.001) associated with rachitic patients whether males or females. Alkaline phosphatase values were significantly (P < 0.01) higher in male infants 91% of them had levels above 30 K.A. units, while the corresponding percentage of girls was 72%. This indicates that the disease is more severe among males. The study gives added support for the belief that there is a genetic factor in nutritional rickets. PMID- 1295948 TI - Comparative results of the immunogenicity of Edmonston-Zagreb and Schwartz measles vaccines administered to 60 Egyptian infants. AB - The present study was conducted on sixty 9-11 month infants attending a primary care clinic in a rural Giza governorate area. Patients were divided into two groups: the first group comprised 42 infants who were vaccinated with the Edmonston Zagreb measles vaccine strain, whereas the second group comprised 18 infants who were vaccinated with the Schwartz measles vaccine strain. Estimation of measles antibody titer by neutralization testing was determined by the microtiter technique prior to and 4 weeks post vaccination. The overall serconversion rate was 85%. Three infants failed vaccination. The Edmonston Zagreb strain was superior to the Schwartz strain in inducing immunity to non immune infants. The nutritional status of the study group was abnormal in almost 1/2 (29/60) infants and borderline in 1/3 (20/60). PMID- 1295949 TI - Prenatal care in primary health care centers of Al Hassa, Saudi Arabia. AB - The objective of this study was to determine the performance of Al Hassa primary health care (PHC) centers in the scope of prenatal care and to have a baseline data for future evaluation of achievement in that field. A retrospective study was done by collecting information on a pre-designed form from the available records in the PHC centers. The number of registered pregnant ladies for prenatal care in PHC centers was 10,594 which was equal to 58% of the estimated number of pregnant ladies in Al-Hassa, in 1409 H (the official calendar of Saudi Arabia corresponding to 1989). The immunization coverage by tetanus toxoid of the registered pregnant ladies was 66.7% for the first dose and 40.3% for the second dose. Forty six percent of the registered pregnancies was identified by PHC staff as high risk pregnancy. It was found that 64.4% of the high risk pregnancy was due to causes in the reproductive history, 25.4% due to associated medical conditions and 7.2% due to causes in the present pregnancy. A self criticism and future need to improve prenatal services are discussed. PMID- 1295950 TI - Factors affecting birth weight in Kuwait. Part II: Pregnancy characteristics and health factors. AB - The aim of this was to determine the mean birth weight of Kuwaiti infants, the incidence of low birth weight and the impact of maternal age, smoking, health status, parents' consanguinity and pregnancy characteristics on infants' birth weight. The study was conducted in the major maternity hospital in Kuwait where the body weight of 1995 newborn infants was recorded shortly after birth. Data describing maternal age, duration of pregnancy, sex of the infant and maternal illness during pregnancy were recorded. Mothers were interviewed to collect data on duration between present and last pregnancy, birth order of the infant, parents' consanguinity and frequency of smoking. The results show that the mean birth weight was 3.5 Kg and the incidence of low birth weight was 3.4%. The results illustrate that young mothers were more liable to have small infants while old mothers were more liable to deliver a very heavy or low birth weight infant. The weight of the newborn infant was positively correlated with duration of pregnancy, duration between present and last pregnancy and birth order. The mean birth weight of male infants (3.51 Kg) was higher than females (3.47 Kg). Parents' consanguinity and maternal smoking had a slight effect on infants' birth weight. The results show that diabetic mothers delivered large babies. On the contrary, the incidence of low birth weight was highest (7.0%) among infants of hypertensive mothers. PMID- 1295952 TI - Patient satisfaction with hospital services: determinants and level in a hospital in Kuwait. AB - The present study used a well-tested patient satisfaction measuring instrument to identify the determinants of the level of overall satisfaction with hospital services, and to examine the level of satisfaction with attributes of 7 specific dimensions of hospital services. Using multiple regression analysis, it was found that out of 12 patient characteristics, age was the most important determinant of overall satisfaction, followed by gender. Perceived health status, clinical department, and expectations about the quality of services before admission were also significant but less important determinants of overall satisfaction. Marital status, level of education, nationality, and previous hospitalization in the study hospital, in Kuwait, or in a western country hospital, all had no significant effect on overall satisfaction. Concerning the effect of satisfaction with specific dimensions of hospital services on overall satisfaction, it was found that satisfaction with physicians was the most important determinant of overall satisfaction, followed by satisfaction with housekeeping and with nurses. Satisfaction with hospital environment and facilities and with admission process were also significant but less important determinants of overall satisfaction, while satisfaction with food and radiology services did not affect overall satisfaction. The level of overall satisfaction as well as satisfaction with specific dimensions of hospital services were quite high. Physicians' care was the most favorably rated dimension, followed by admission process and housekeeping, while nursing care was the least favorably rated dimension. Among the attributes of physicians' and nurses' care, technical care and courtesy were the most favorably rated items; while communication, particularly imparting of information, was the least favorably rated aspect. Several attributes of the hospital environment and facilities and of the food services were found to be dissatisfying to patients. PMID- 1295951 TI - Vaccination coverage before and after primary health care implementation and trend of target diseases in Al Hassa, Saudi Arabia. AB - There were two objectives of this study. The first was to determine the impact of vaccination coverage in the first year of life on the trend of the expanded program of immunization (EPI) target diseases in Al Hassa. The second was to determine the impact of primary health care (PHC) implementation in Al Hassa on vaccination coverage. A correlation matrex was computed for all the variables to determine the correlation between vaccination coverage by type of vaccine and reported cases of EPI target diseases. A negative correlation was noticed between Bacillus Calmette Guerin (BCG), Oral Polio Vaccine (OPV), Diphtheria, Pertussis and Tetanus (DPT) and measles vaccine and reported cases of corresponding diseases. This negative correlation was significant (P = 0.043) between measles vaccine and reported measles cases. The average vaccination coverage in the first year of life based on the total number of births significantly increased in 1988 and 1989 compared to the preceding four years (P < 0.01). It is concluded that with increased vaccination coverage in the first year of life against EPI target diseases, the number of reported corresponding diseases decreased, and that PHC implementation improved the vaccination coverage in Al Hassa. PMID- 1295953 TI - Childhood aggression, adolescent delinquency, and drug use: a longitudinal study. AB - The interrelation of childhood aggression, early and late adolescent delinquency, and drug use was explored. Data were obtained for the subjects when they were 5 10 years old. Follow-up interviews were conducted when the subjects were between 13-18 years old and again when they were 15-20 years old. A LISREL analysis of the three waves of data indicated that childhood aggression is a precursor of adolescent drug use and delinquency, and that early adolescent drug use is correlated with contemporaneous delinquency as well as with later drug use and delinquency. PMID- 1295954 TI - Effects of list organization and retrieval cues on children's delayed recall. AB - Developmental differences in recall were investigated as a function of mode of presentation (blocked vs. random), recall condition (cued vs. noncued), and time of recall (immediate vs. delayed). Ninety-six second graders and 96 fourth graders were the subjects, and the stimuli were 20 pictured items from five categories. Data on three dependent variables (item recall, category recall, and clustering score) were analyzed. Immediate recall was better than delayed recall, the fourth graders' overall performance was superior to that of the second graders, and the blocked presentation of items and the presence of retrieval cues at recall enhanced recall and organization in recall. Furthermore, an analysis of a three-way interaction on two dependent measures indicated that, in the noncued condition, immediate recall was better than delayed recall for children in both grades. However, in the cued condition, the fourth graders performed better during delayed recall than during immediate recall, whereas the second graders did better during immediate recall than during delayed recall. PMID- 1295955 TI - Parental practices, support system failures, self-concepts, and evaluations of parents. PMID- 1295956 TI - Implementing dietary recommendations. PMID- 1295957 TI - A social-psychological perspective of dietary quality in later adulthood. AB - Nutrition has been implicated in the quality of life of older adults, beyond proving essential nutrients and calories. Recent concern about malnutrition has prompted a broader social-psychological approach to nutrition and aging research. The present investigation examined the relationship of self-actualization and social support to dietary intake. Data from 100 community-dwelling adults, ages 60-83 years, revealed significant and positive associations between the predictor variables and vitamin A, B vitamin complex, iron, and dietary fiber. Specifically, the personality trait of being internally motivated and the presence of support from family, friends and neighbors were found to positively influence dietary quality. PMID- 1295958 TI - Vitamin B12 and folate status of a selected group of free-living older persons. AB - Vitamin B12 and folate status was determined in 50 male and 47 female free-living subjects (65-77 years) in winter and summer. The mean intake calculated from 3 day food records met the Canadian recommended intake (RNI) for both gender and season, however, probability analysis of dietary data revealed a number of subjects at risk of deficiency. Although the mean plasma levels were within the acceptable range for both vitamins, some 9 to 14% of individual subjects had folate plasma levels below normal. Fewer subjects had subnormal plasma vitamin B12 levels. Although mean values for dietary intake and plasma concentration of folate and vitamin B12 may indicate nutritional adequacy, a proportion of an older population may be at nutritional risk. PMID- 1295959 TI - Hemorrhagic emergencies in obstetrics. PMID- 1295960 TI - Vulnerability: a conceptual model applied to perinatal and neonatal nursing. PMID- 1295961 TI - Antepartum vulnerability: stress, coping, and a patient support group. PMID- 1295962 TI - Vulnerability in family systems: application to antepartum. PMID- 1295963 TI - Vulnerability of homeless pregnant and parenting adolescents. PMID- 1295964 TI - Platelet vulnerability in the fetus/neonate with neonatal alloimmune thrombocytopenia. PMID- 1295965 TI - Decision making and the vulnerable high-risk neonate: international perspectives. PMID- 1295966 TI - Vulnerability as a consequence of the neonatal nurse-infant relationship. PMID- 1295967 TI - Maternal perception and parent-infant interaction of vulnerable cocaine-exposed couplets. PMID- 1295968 TI - Rehabilitation R & D Progress Reports 1991. PMID- 1295969 TI - [Epidemiology of emergency department hospitalizations for poisoning by industrial products]. PMID- 1295971 TI - [Acute liver and kidney failure after the ingestion of cyclohexanone]. PMID- 1295972 TI - [Cytolytic hepatitis following ingestion of monochlorobenzene. Two cases]. PMID- 1295970 TI - [Chemical burns of the upper digestive tract and cytolytic hepatitis following ingestion of a mixture of methyl ethyl ketone peroxide, diacetone alcohol and diisobutyl phthalate]. PMID- 1295973 TI - [Six cases of acute poisoning by aromatic amines]. PMID- 1295974 TI - [Skin and eye burns, painful abdomen syndrome, Antabuse effect, and cytolytic hepatitis in workers exposed to dimethylformamide]. PMID- 1295975 TI - [Decapex poisoning. 15-year evaluation at the Poison Control Center of Paris]. PMID- 1295976 TI - [Encephalopathy due to repeated voluntary inhalation of paradichlorobenzene]. PMID- 1295977 TI - [Exposure to halogenated volatile anesthetics and professional activity]. PMID- 1295978 TI - [Is it useful to measure ionized fluorine in the urine to monitor occupational exposure to halothane?]. PMID- 1295979 TI - [Phosgene poisoning in the Toulouse area. Importance of a phosgene detection badge in industrial medicine and disaster medicine]. PMID- 1295980 TI - [Carbon monoxide poisoning caused by wall-paper stripper]. PMID- 1295981 TI - [Acute acrolein poisoning from exposure to the thermal degradation products of a vegetable fat]. PMID- 1295982 TI - [Acute poisoning by arsine in a ferrous metal foundry]. PMID- 1295983 TI - [The syndrome of chemical odor intolerance]. PMID- 1295984 TI - [Occupational asthma in a mechanic after a single exposure to isocyanates during handyman work]. PMID- 1295985 TI - [Importance and limitations of alveolar air in monitoring the risk of occupational exposure to volatile solvents: evaluation of a study]. PMID- 1295986 TI - [Skin manifestations accompanying acute arsenic poisoning and its treatment]. PMID- 1295987 TI - [Occupational chronic mercury poisoning. Two cases]. PMID- 1295988 TI - [Urinary excretion of mineral arsenic, methylarsonic acid and dimethylarsinic acid in workers exposed to gallium arsenide]. PMID- 1295989 TI - [Two cases of zinc chloride burns in a polyester film coating workshop]. PMID- 1295990 TI - [Lead poisoning, a present-day disease. Monitoring difficulties]. PMID- 1295991 TI - [Lead poisoning in children. Validation of a 5-hour urinary lead provocation test]. PMID- 1295992 TI - [Treatment of the ingestion of caustic substances]. PMID- 1295993 TI - [Cyanide poisoning. Evaluation of 15 years of phone calls to the Anti-Poison Center and autopsies at the Institute of Forensic Medicine]. PMID- 1295994 TI - [Phlebitis of the lower limbs. Which is the test of first choice today, Doppler echography? Phlebography?]. PMID- 1295995 TI - [Prospective study of echography versus phlebography in the detection of sural venous thrombosis]. AB - Among all noninvasive techniques, high-resolution ultrasonography used alone has rarely been used for the diagnosis of thrombosis in the calf. Nineteen patients with suspected AVT were examined with ultrasonography and phlebography during 4 months. For each patient, a sonogram and a phlebogram were taken within less than 24 hours and interpreted independently. The sonographic exploration with a high resolution (5 MHz) transducer covers all deep trunks and muscular veins (soleus or gastrocnemius muscles). The positivity criterion is the persistence of a hypoechogenic endoluminal image under moderate compression. According to the phlebographic data, 65% of the patients present with thrombosis. Ultrasonography has a sensitivity of 95% and a specificity of 99% for the study of the deep trunks. Ultrasonography screens more thromboses than phlebography (23 cases versus 17). On a whole, ultrasonography seems to be more sensitive than phlebography for the diagnosis of recent sural thrombosis. PMID- 1295996 TI - [Arnold-Chiari malformation. Contribution of cerebral echography in the pretherapeutic evaluation]. AB - From August 1988 to August 1989, we performed pre-operative sonographic examinations on eleven children who had Arnold-Chiari malformation (ACM). All children presented with myelomeningocele. ACM was the leading cause of hydrocephalus in infants and newborns. For eight children, hydrocephaly was particular by the discrepancy between the dilated atrium and the relatively small temporal horns. Two children have associated extra-neurologic malformations. Five patients were operated upon, with poor results in four. In our experience, ultrasonography was found very useful in patients presenting with myelomeningocele. PMID- 1295997 TI - [Cerebral miliary tuberculosis. Apropos of 5 cases and review of the literature]. AB - The authors report 5 cases of cerebral miliary tuberculosis studied by computerized tomography and review 5 cases of the literature. Computerized tomography can see very small tuberculomas, of several millimeters. Chest miliary tuberculosis is found in all their cases, and 3 of the 5 cases of the other authors. Because of the discretion of neurological signs and the association with chest miliary, we suggest to make a computed tomography of brain of all patients who have chest miliary tuberculosis despite the absence of neurological signs and we think that we will find out other cases of brain miliary tuberculosis. PMID- 1295998 TI - [MRI of the spinal epidural fat in pathology]. AB - The authors report about their experience with the merits of the normal systematization of epidural fat with MRI. On sagittal sections, this fat has a variable appearance, but its location along the spinal canal is constant. On axial sections, its morphology is suggestive of the level of section: cervical, upper or lower thoracic, lumbar. Some changes in this fat are precious data to explain local hypertrophy (scoliosis) or to locate an intra- or extradural process. PMID- 1295999 TI - [Thoracic lymphoma and AIDS]. AB - During the past 4 years, 122 patients with AIDS and 20 with thoracic lymphoma associated to AIDS were observed. There were 18 cases of non-Hodgkin's lymphoma, mostly at a high grade and a high b-cell stage (Burkitt's or Burkitt-like lymphoma) (16 cases). This prevalence reflects the general increase in the number of neoplasms secondary to immunosuppression, which goes along with the improvement of prevention and the control of opportunistic infections. Out of these 20 lymphomas in AIDS, 5 (25%) produced thoracic lesions; in 4 cases, the initial site of the disease was in a thoracic site. The frequency of such expressions is greater that reported in the literature. The radiological appearances are atypical relative to the classical signs of lymphoma in the general population, with predominantly nodular forms (60%) or peripheral, fast growing masses that are likely to invade the thoracic wall. Isolate lymph node invasion is possible, as well as pleural effusion. Though not pathognomonic, this appearance is highly suggestive of lymphoma in AIDS (LDS) in HIV-positive patients. In all patients with pulmonary lymphoma, CT showed bilateral lesions in a greater number than plain radiography had shown, with morphological and CT appearances that allowed a correct approach of the diagnosis and an appropriate choice of the site of biopsy. PMID- 1296000 TI - [What may be expected from endorectal echography and magnetic resonance imaging in the evaluation of local extension of cancer of the prostate?]. AB - Thirty patients presenting with a clinical stage A or B cancer underwent TRUS and MRI with a body coil prior to radical prostatectomy. Imaging and pathology were correlated to assess the limits of TRUS and MRI in pre-operative staging of prostatic carcinoma. Results showed that TRUS and MRI had a sensitivity of 42 and 66% and a specificity of 89 and 94% respectively, for the diagnosis of macroscopic capsular effraction. Seminal vesicle invasion was diagnosed by TRUS with a sensitivity of 16% and a specificity of 81%. With MRI, the sensitivity and the specificity were 85 and 94% if only gross infiltration was considered. Sensitivity dropped to 45% if microscopic invasion was included. We conclude that: 1) postero-lateral venous plexus are more easily delineated by MRI, permitting a more accurate diagnosis of capsular penetration. 2) Seminal vesicle invasion cannot be diagnosed by TRUS as the echo-structure of the cancer and the caudal junction of the seminal vesicles and vas deferent are similar. 3) A normal caudal junction on TRUS or a normal bilateral hypersignal of the seminal vesicles on MRI are associated with seminal vesicle invasion in less than 5% of cases. 4) A normal caudal junction on TRUS eliminates false positive cases of MRI related to non tumoral hyposignals of the seminal vesicles. PMID- 1296001 TI - [Renal lymphoma in a patient after kidney transplantation and cyclosporine therapy]. AB - The effectiveness of renal transplantation has been considerably improved by the use of cyclosporine as an antirejection agent. However, because of those very same immunosuppressive properties, this substance may lead to several infectious or tumoral complications that raise complex therapeutic problems. This article reports about one case of immunoblastic lymphoma discovered in a patient who received renal transplantation and who had been treated with cyclosporine for two years. PMID- 1296003 TI - [Organization of medicine in Romania]. PMID- 1296002 TI - [The role of the radiologist in the medicolegal procedure after an aviation accident]. AB - The role of radiologic imaging studies in the forensic medical procedure following an airborne disaster is now well established. This report summarizes the experience and the results acquired with a recent air crash, and insists on three suggestions: the necessity of a prepared identification team consisting of specialist in forensic medicine, in forensic odontology and specialist in forensic radiology, and the usefulness of a suitable structure for the study and the storage of the dead bodies, the need for a compilation of radiological informations, notably dental X-Ray examinations for the flying personnel. PMID- 1296004 TI - The economics of hypertension control: some basic issues. PMID- 1296005 TI - Societal value of health and the prevention of cardiovascular disease. PMID- 1296006 TI - Review of the benefits of treating hypertension. AB - The main points covered in this review are as follows: 1. Hypertension is a major determinant of cardiovascular disease (CVD). As such it is a major cause of mortality, potential years of life lost, morbidity and long-term disability. 2. The incidence of CVD is directly related to BP. It is likely that this extends over the full range of BP although some writers believe that a J-curve of risk exists for CHD. 3. The relationship between long-term disability from CVD and BP requires further study. 4. Because of regression dilution bias, the gradient in risk of stroke and CHD with BP has been underestimated in the past. Recent research suggests that the risk of stroke increases at least tenfold and CHD sixfold over a range of usual DBP of 30 mmHg (equivalent to approximately 50 mmHg baseline DBP). 5. The population attributable risk (PAR) of CVD related to general elevation of BP in the population from a mean daily excess of sodium intake of 100 mmol/day is at least 30%. In typical industrialised countries the PAR for stroke and CHD from clinical hypertension is 36% and 22%, respectively. These estimates of PAR provide a guide to the maximum benefit that could result from either restriction of sodium intake in the whole population or ideal management of all persons with hypertension. In practice such targets are unlikely to be realised. 6. Recent analyses of clinical trials of treatment of hypertension suggest that the risk of stroke is reduced at all levels of initial BP to the extent predicted from observational studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296007 TI - Cost effective analyses in the treatment of high blood pressure. PMID- 1296008 TI - Cost of hypertension treatment and the price of health. PMID- 1296009 TI - The hypertensive patient beyond blood pressure. PMID- 1296010 TI - Considerations regarding the cost and effectiveness of public and patient education programmes. AB - For nearly two decades, the National High Blood Pressure Education Programme has administered a programme of public, patient, and professional education in an effort to reduce uncontrolled hypertension, an important public health problem in the USA. A broad network has been established and many partners have joined forces to form the NHBPEP. During the tenure of the programme, awareness, treatment, and control rates for high BP have increased dramatically, and this has been associated with a nearly 57% reduction in age adjusted stroke mortality. In 1988, stroke cost this nation about $23.3 billion a year in direct and indirect costs. Much of this is attributed to uncontrolled hypertension. It seems likely that controlling hypertension saved nearly $1.5 billion in direct and indirect costs for stroke in one year alone. This is in addition to the other health care costs attributed to coronary heart disease that have been reduced as a result of treating high BP. A portion of this may be related to the NHBPEP. PMID- 1296011 TI - Community attributable risk: its economic dimensions. PMID- 1296012 TI - Costs and benefits of community programmes for the control of hypertension. PMID- 1296013 TI - Cost of hypertension in Spain. PMID- 1296014 TI - Does hypertension management audit provide cues for cost containment? Hypertension Management Audit Project Group. PMID- 1296015 TI - Relative costs of antihypertensive drug treatment. PMID- 1296016 TI - Assessing the economic value of antihypertensive medicines. PMID- 1296017 TI - Summary statements by workshop participants: working group discussions and reports. PMID- 1296018 TI - Panel discussion: cost containment and ethics- incompatible or complementary? PMID- 1296019 TI - [Acute toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in mice, rats and dogs. AB - Single oral, subcutaneous or intravenous administration to mice and rats and oral administration to dogs were performed to investigate the acute toxicity of FUT 187. 1) LD50 values in mice were 4,395 mg/kg for males and 3,626 mg/kg for females orally, 6,284 mg/kg for males and 5,492 mg/kg for females subcutaneously, and 39.4 mg/kg for males and 41.4 mg/kg for females intravenously. In rats, these values were 4,653 mg/kg for males and 3,761 mg/kg for females orally, 6,799 mg/kg for males and 3,343 mg/kg for the females subcutaneously and 21.8 mg/kg for males and 15.8 mg/kg for females intravenously. 2) Death occurred 2 hours after administration in a male dog of the 3,000 mg/kg group just after convulsion and nasal discharge were observed. 3) General symptoms in mice and rats included a creeping gait, convulsion, singultus, cyanosis, decreased locomotor activity, piloerection and salivation which were commonly observed by all routes. All dogs showed vomiting and decreased locomotor activity; the prone or lateral position, crouching, ataxic gait and salivation were also observed in many cases. 4) On autopsy, changes attributable to local irritation by FUT-187 were seen in all species except mice and rats dosed intravenously. For the gastro intestinal-tract (GIT), inflammation of the stomach, adhesions between the stomach and the liver and sclerosis, petechiae or ulcer were observed in mice and rats dosed orally. In the subcutaneous route, retention of the test compound and necrosis at the injection site were observed. Reddening and loss of mucosal smoothness were observed in the GIT of a dog which died; desquamation, congestion, hemorrhage and retention of tested compound in the digestive mucosa were observed on histopathology. PMID- 1296020 TI - The evaluation of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) by oral administration in cynomolgus monkeys in a 13 week subacute toxicity study. AB - To assess the subacute toxicity of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) a 13 week subacute toxicity study by gavage was done in Cynomolgus monkeys at dosage levels of 0, 15, 45 and 135 mg/kg/day. Deaths were seen in the 135 mg/kg/day group; with associated debility. The animals that died had high plasma levels of FUT-187. Little weight gain was seen in the 135 mg/kg/day group. There were no clear treatment related effects on ophthalmoscopy or electrocardiography or on hematological, biochemical or urinalysis. There were no effects noted at necropsy or on histopathology and the causes of death for each of the 3 animals that died were suppurative glomerulonephritis, bone marrow depression and possible gavage injury respectively. The no-effect level for toxicology was considered to be 45 mg/kg/day. PMID- 1296021 TI - [A 52-week oral chronic toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in rats with a recovery period of 5 weeks. AB - The chronic toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 0.4, 2, 10, 50 and 250 mg/kg/day for 52 weeks. The drug was then withdrawn for 5 weeks. The results are summarized as follows: There were no deaths or toxic signs caused by the drug throughout the experimental period. There were no drug-related changes in food consumption, ophthalmological examination, hematology or blood chemistry. Slight suppression of growth was observed in males in the 250 mg/kg group. This change was reversed on withdrawal of the drug. Drug crystals were observed in the urinary sediments of both sexes in the 250 mg/kg group, but this change disappeared on withdrawal of the drug. Gross pathological examination revealed the following changes: enlargement and nodule formation in the pancreas in both sexes given more than 10 mg/kg of the drug; dark red spots in the glandular stomach in males in the 250 mg/kg group; thickening of the small intestinal walls in both sexes given more than 50 mg/kg. Of these organs, no changes were observed in the stomach and small intestine at the end of the recovery period. Increased pancreas weight was observed in both sexes given more than 50 mg/kg of the drug. Examination at the end of the recovery period suggested reversibility, showing a lesser degree of change. Histopathological examination revealed the following changes in the pancreatic acinar cells: acidophilic foci and nodules in both sexes given more than 10 mg/kg of the drug; adenoma in one male in the 250 mg/kg group; increased zymogen granules in both sexes given more than 50 mg/kg of drug; fine vacuolization in females in the 250 mg/kg group. At the end of the recovery period, increased zymogen granules and fine vacuolization of the acinar cells were not found. Furthermore, erosion or healed erosion in the glandular stomach, duodenum and jejunum was observed in a few males or females in the 250 mg/kg group, but those changes disappeared after the recovery period. In the liver, altered cell foci was observed more frequently in males in the 250 mg/kg group than the other groups, but this change also disappeared after the recovery period. In addition, brown pigmentation in the proximal renal tubules of the kidney was observed in both sexes in the 250 mg/kg group, but lesions observed in the examination after the recovery period were less noticeable than in the examination at the end of the administration period. PMID- 1296022 TI - [A 52-week chronic oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) in dogs]. AB - A chronic oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol 2-yl)amino] benzoate dimethanesulfonate (FUT-187), a new protease-inhibiting agent, was carried out using male and female beagle dogs. FUT-187 was orally administered to the dogs at dose levels of 7.5, 15, 30 and 60 mg/kg/day for 52 weeks, followed by 5 weeks' recovery period. Results are summarized as follows: 1. In general conditions, vomiting, salivation and the passage of mucousy stools were observed in dogs given 15 mg/kg/day or more, and diarrhea was observed at 30 mg/kg/day or more. One male given 15 mg/kg/day showed transient pallidity of the oral mucosa, and another male in the same group showed apnea and abdominal breathing. In addition, one male given 30 mg/kg/day was euthanatized due to extreme weakness, as weight loss and pallid oral mucosa, and another male in the same group died after showing acute toxic symptoms such as hyperpnea, tonic convulsion and ataxic gait. 2. Weight gain was slightly suppressed in females given 60 mg/kg/day. No significant changes in food consumption were observed. 3. Hematological examination revealed no statistically significant changes. Decreases in RBC counts, Ht values and Hb concentrations, and increased reticulocyte counts were observed in one male of 15 mg/kg/day group, which also showed pallid oral mucosa, and in one male of the 30 mg/kg/day group, which was euthanatized in a moribund state. 4. Blood biochemistry revealed increased GPT activity in males given 15 and 30 mg/kg/day and females given 60 mg/kg/day, which was accompanied by sporadic increases in GOT, A1P and/or gamma-GTP activities. Males given 30 mg/kg/day or more showed decreased total protein. 5. Hepatic function testing (ICG test) showed no statistically significant changes. One female given 60 mg/kg/day showed increased accumulating concentration of ICG. 6. There were no toxicological changes in urinalysis, fecal occult blood, renal function (PSP clearance), ophthalmological and electro-cardiographic examinations. 7. In pathological examination, inflammatory cell infiltration and microgranuloma formation in liver were noted periportally or perivenularly in both sexes given 15 mg/kg/day or more (except for 30 mg/kg/day males). In the some cases, atrophy, degeneration and necrosis of hepatocytes and/or fibrosis around inflammatory cells and microgranuloma were observed. In the spleen, one male given 15 mg/kg/day and one female given 60 mg/kg/day showed increased plasma cells in the red pulp. In the case sacrificed in a moribund condition, findings in the liver and spleen similar to those in surviving cases were detected, but were more severe, and the liver showed diffuse fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296023 TI - [A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro 1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in rats]. AB - The toxicity of FUT-187, a synthetic protease inhibitor, was investigated in Sprague-Dawley rats. FUT-187 was given orally to the rats at doses of 2, 10, 50, 250 and 1250 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks for recovery. The results are summarized as follows: In the 1250 mg/kg/day group, 9 out of 20 males died with decreased body weight and exhaustion. Histopathological examination revealed renal papillary necrosis, ulcer in the urinary bladder, hemostatic lesions in the lungs and liver, ulcer or erosion in the stomach, duodenum and jejunum. The surviving animals in this group showed swelling of the limbs due to synovitis, transient salivation immediately after administration, suppression of growth with decreased food consumption. Urinalysis revealed a low pH, increased ketones and bilirubin excretion, dark yellowish change in color, the appearance of "leaflet-shaped" crystals and increased red blood cells and epithelial cells in the urinary sediment, increased water intake, decreased specific gravity and decreased sodium, potassium and chloride in the urine. Hematologically, there was an increase in the white blood cell count. A biochemical analysis of the blood revealed decreased amylase activity, glucose and total protein levels and increased GOT activity and inorganic phosphorus levels. Pathological changes were observed in the pancreas, kidney, digestive tract, urinary bladder and liver. The pancreas showed macroscopical enlargement and increased organ weight. Histopathologically, there were several alterations in the acinar cells, such as vacuolization due to increased fat droplets, nuclear irregularity, prominent nucleoli, irregular arrangement and vesiculation of rough endoplasmic reticulum (rER), dilatation of developed Golgi apparatus and increased free ribosomes. In the kidney, increased weight and pigmentation in the proximal tubular epithelium were noted. Electron microscopically, these pigments were recognized as secondary lysosomes containing filamentous material and electron dense granules within a lucent matrix. In the digestive tract, ulcer or erosion in the stomach and duodenum, and villous proliferation in the small intestine were observed. Furthermore, hyperplasia and vacuolization were noted in the mucosal epithelium of the urinary bladder. In addition, loss of perilobular fat droplets in the liver and increased adrenal weight without histological change were observed. After a 5-week recovery period, these changes disappeared almost completely. In the 250 mg/kg/day group, slight suppression of growth the appearance of "leaflet-shaped" crystals in the urinary , sediment, increased water intake and decreased sodium in the urine were observed. The pancreas showed enlargement, increased weight, acinar cell hypertrophy with increased zymogen granules, fine vacuolization, slight derangement and vesicular of rER, and dilatation of Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296024 TI - [Reproductive and developmental toxicity studies of FUT-187. (I)--Fertility study in rats with oral administration of FUT-187]. AB - FUT-187 was given orally at 20, 120 and 720 mg/kg during the pre-pairing period (63 days prior to pairing in males and 14 days prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (days 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. One male of the 720 mg/kg group died due to treatment. Temporary salivation was observed in males and females in the 20 mg/kg or more groups. In males, increases in the weight of the pancreas in the 120 mg/kg or more groups and the adrenals in the 720 mg/kg group, a depression of body weight gain and decreases in food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In females, an increase in the weight of the pancreas in the 120 mg/kg or more groups, a slight depression of body weight gain during the early stage of pregnancy and a decrease in the food intake, and a decrease in the weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. No dose-related changes were found in the estrus, copulation, insemination and fertility indices. In fetuses, decreased numbers of corpora lutea, implantation and live fetuses were observed in the 720 mg/kg group. There were no treatment-related abnormalities in fetal mortality, sex ratio, weights of fetuses and placenta, and external and visceral examinations. Based on these results, it is concluded that the no-effect-dose levels of FUT-187 are less than 20 mg/kg for the parents, 720 mg/kg for reproductive performance and 120 mg/kg for fetal development. PMID- 1296025 TI - [Reproductive and developmental toxicity studies of FUT-187. (III)--Postnatal study in rat F1 offspring from dams treated orally with FUT-187 during the period of fetal organogenesis]. AB - A postnatal study of F1 offspring exposed to FUT-187 during fetal organogenesis was carried out using Crj : CD rat. FUT-187 was dosed by gavage at 0, 50, 200 and 800 mg/kg/day from day 7 to 17 of gestation. All pregnant rats were allowed to deliver newborns, and F1 offspring were examined for development indices and reproduction and learning ability. Effects at 800 mg/kg included temporary salivation, body weight depression and decreased food intake. There were no adverse effects on delivery and lactation and no significant changes on neonatal development, growth, reproduction and learning ability in the F1 offspring. These results indicate that the no effect dose level of FUT-187 is 200 mg/kg/day in dams, and 800 mg/kg/day in offspring. PMID- 1296026 TI - [Reproductive and developmental toxicity studies of FUT-187. (V)--Perinatal and postnatal study in rats with oral administration of FUT-187]. AB - FUT-187 was given orally at 20, 120 and 720 mg/kg to female rats during the perinatal and postnatal periods and the effect on dams and offspring were evaluated. One dam during the terminal period of gestation and 3 dams after delivery in the 720 mg/kg group died due to FUT-187. In dams, an increased pancreas weight in the 20 mg/kg or more groups, temporary salivation after dosing in the 120 mg/kg or more groups, and a depression of body weight gain and decreased food intake and weight of the carcass in the 720 mg/kg group were statistically significant in comparison with controls. In offspring, postnatal death rate in the 720 mg/kg group tended to increased. Decreased body weight gain and delayed appearance of abdominal hair and descent of testis in the 720 mg/kg group were statistically significant in comparison with controls. There were no treatment-related abnormalities in visceral examination, organ weight, skeletal examination, sensory function, behavioral function, learning ability or reproductive function. Based on these results, it is concluded that the no-effect dose levels of FUT-187 are less than 20 mg/kg for dams, and 120 mg/kg for reproductive performance of dams and offspring development. PMID- 1296027 TI - [Antigenicity study of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2 yl)amino] benzoate dimethanesulfonate (FUT-187) in guinea pigs and mice. AB - Antigenicity study of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2 yl)amino] benzoate dimethanesulfonate (FUT-187), a new protease inhibitor, was investigated in guinea pigs and mice and the following results were obtained. 1. In guinea pigs immunized with FUT-187 plus adjuvant by intramuscular/subcutaneous routes, ASA, ACA and PCA reactions challenged intravenously or intradermally were positive. 2. In guinea pigs immunized with FUT-187 plus adjuvant by intramuscular/subcutaneous routes, ASA and PCA reactions challenged orally were negative. 3. In guinea pigs immunized with FUT-187 by the oral route, ASA, ACA and PCA reactions were negative. 4. In guinea pigs immunized with IABA and AN plus adjuvant by intramuscular/subcutaneous routes, ASA and PCA reactions were negative. 5. 48-hr PCA reactions were elicited with sera obtained from BALB/c and C3H/He mice immunized with FUT-187 plus adjuvant by the intraperitoneal route, responses were negative. 6. From the results of hapten inhibition tests using anti-FUT-187 guinea pig serum, it is suggested that the antigenicity of FUT-187 is attributable to the its benzoic acid. PMID- 1296028 TI - [A 13-week subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro 1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) in dogs. AB - A subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187), a new protease inhibiting agent, was carried out in beagle dogs of both sexes. FUT-187 was administered to dogs at daily oral doses of 15, 50 and 150 mg/kg. Dogs in 150 mg/kg group were given twice a day in a.m. and p.m.. The results were as follows: 1. Changes of physical sign attributed to FUT-187, consisted of vomiting, diarrhea, salivation, decrease of locomotor activity, sedation and hyperemia of eye mucosa. These changes expect vomiting vanished within about 2 hours after treatment. One male given 150 mg/kg died on day 19 and two females given 150 mg/kg were sacrificed on day 55 and 67 due to deterioration of systemic conditions. 2. Body weight gain was suppressed in males given 150 mg/kg and females given 50 mg/kg or more. 3. In hematological examinations, some changes suggesting anemia or inflammation were observed in a few animals received 50 mg/kg or more 4. In serum biochemical examinations, dogs given 50 mg/kg or more had decrease of albumin, total protein, A/G ratio and total cholesterol, increase of GPT activity. In liver function test, decrease of function was observed in a few animals in 150 mg/kg group. These changes diminished by the end of recovery period. 5. In autopsy findings, ulcer formation and desquamation of mucosa in the digestive tract were observed in dead or sacrificed animals and survived animals given more than 50 mg/kg. In sacrificed animals, liver was yellow in color and intussusception was seen. 6. Plasma levels of intact FUT-187 and metabolites on the day 37 or 83 were higher than that on the first day of administration. 7. In histopathological examinations, ulcer formation, desquamation, degeneration and/or atrophy of mucosa in the digestive tract were observed in the animals from 50 mg/kg and 150 mg/kg groups. In addition, fatty deposition in hepatocytes was observed in one dead animal and two sacrificed animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296029 TI - A simple animal model for inducing and releasing surgical jaundice in rats. AB - Surgical jaundice can be easily induced by ligation of bile duct, but it is not easy to reverse the ligation in rats. Therefore, a simple method was designed in our laboratory to address the problem. Obstruction of bile duct can be achieved by the compression by two arms of a fine silicon tube enveloped in an outer bigger silicon tube. Both silicon tubes are then fixed and sutured to the abdominal peritoneum. Therefore, if the releasing of the obstruction is required, removal of the inner fine silicon tube by removing off the previous suture tire of silicon tube which had settled under the skin. Thus, the reversing of obstruction could be achieved without extensive exploration into the abdominal cavity. One week after obstruction the bile duct of rats were dialated 6.10 +/- 1.26 mm (Mean +/- SD) in rats. The serum bilirubin and alkaline phosphatase were 6.29 +/- 1.26 mg% and 229.30 +/- 82.22 IU respectively. The dilated bile duct decreased into 3.00 +/- 0.98 mm one week after decompress with this method. Serum bilirubin and alkaline phosphatase were 1.80 +/- 0.79 mg% and 90.50 +/- 19.60 IU respectively. It proved that this animal model was simple and had the benefit of being able to sample the bile without contamination with intestinal contents after decompression. PMID- 1296030 TI - Ultrasonography of chest diseases: analysis of 154 cases. AB - Sonographic characteristics of various chest diseases in 154 cases were analysed according to margin of the lesion, internal echogenecity, posterior echo enhancement, air bronchogram etc. We intended to present the basic sonographic patterns of common chest diseases. The study included 10 normal cases, 10 cases with lung abscesses, 31 cases of pneumonia, 24 cases of tumors, 11 cases of obstructive atelectasis, 8 cases of pleuropericarcadial effusions, 10 cases of minimal effusions, 6 cases with pleural thickening, 32 cases of massive pleural effusion with simple compression atelectasis and 12 cases of pneumonia with parapneumonic effusion. Sonographically, normal lung showed hyperechoic zone beneath the chest wall. Identification of arc or ring-shaped wall favored lung abscess. Air bronchogram could only be found in pneumonia. Mass showed various internal echogenecity. The internal echogenecity in obstructive atelectasis was very homogeneous which could not be found in tumor. Pleural thickening showed linear hyperechogenecity beneath the chest wall. In minimal effusion, the line of the diaphragm could be easily identified. Pleuropericardial effusion could be easily diagnosed by chest sonography. The line of the pericarcadium could be clearly identified. The internal echogenecity of massive effusion were various. The internal echogenecity of simple compression atelectasis showed very homogeneous hyperdense internal echogenecity. The internal echogenecity of lung parenchyma in pneumonia with parapneumonic effusion was similar to that of pneumonia. Obstructive atelectasis, mass, consolidation and encapsulated effusion could be differentiated by chest sonography without much difficulty. Sonography could aid chest radiography by giving more morphologic information and was cheaper than computed tomography. PMID- 1296031 TI - Maximum inspiratory pressure: a neonatal criterion for weaning from mechanical ventilation. AB - Thirty-three newborn infants admitted to the neonatal intensive care unit of our hospital were studied. Mechanical ventilation was used for more than 24 hours for each patient. Maximum inspiratory pressure (MIP) was measured by means of a manometer at the oral end of the endotracheal tube just prior to extubation. Of the 33 studied neonates, 28 were successfully weaned at the first attempt of extubation (group I). Five neonates failed at the first attempt of extubation and required tracheal reintubation (group II). The mean birth weight was 1.78 +/- 0.86 kg, the mean gestational age was 32.6 +/- 4.3 weeks and the mean duration of intubation was 4.2 +/- 2.1 days in group I. The mean birth weight was 1.74 +/- 0.61 kg, the mean gestational age was 32.8 +/- 3.5 weeks and the mean duration of intubation was 7.0 +/- 2.6 days in group II. The mean MIP value in group I was 42.57 +/- 7.18 cm H2O and the mean MIP value in group II before the first attempt of extubation was -21.2 +/- 1.79 cm H2O. The patients in group I had a significantly lower MIP (P < 0.01) than group II, of the 28 patients in group I, 27 had MIP equal to or exceeding -35 cm H2O and only one case had MIP of -30 cm H2O. We conclude that measurement of MIP is a simple, useful and safe method for neonates to predict successful extubation from prolonged mechanical ventilation. A neonate with a MIP exceeding -35 cm H2O can be safely weaned from mechanical ventilation. PMID- 1296032 TI - [Flow cytometric analysis of DNA in esophageal cancer]. AB - Malignancy is the first of the ten leading causes of death in Taiwan area, however, since 1978, esophageal cancer is on the first ten causes of malignancy. Esophageal cancer is an aggressive neoplasm with a generally poor prognosis. This is usually related to the advanced stages of the neoplasm at presentation and at diagnosis. In this study, the DNA content in tumor was analyzed by flow cytometry, and compared it with clinical- pathological data, especially the survival time. All thirty seven cases (36 male, 1 female, mean age: 56.5 +/- 10.3 y/o) received operation at Kaohsiung Medical College Hospital in the past 11 years and 29 cases (27 male, 2 female, mean age: 62.2 +/- 9.6 y/o) proved to be esophageal cancer by endoscopic biopsy were assayed in this study. The formalin fixed-paraffin embedded block is used to analyze DNA content by flow cytometry. After comparing these results with clinical-pathological data, there were no significant difference in sex, age, duration, tumor location and length. However, there is a significant correlation between ploidy and tumor cell differentiation, that is, most of the diploid cells were well differentiated while most of the aneuploid cells were poorly differentiated. The median survival time of diploid cases was 325 days which was longer than the 277 days in aneuploid group, but there was no significant difference between these two groups. The same result was noticed in DNA index. Multiple variables analysis of prognostic factors disclosed that there were significant difference in correation with age tumor location tumor length, and whether there was combined radiotherapy and operation. But there were no significant relationship between survival and DNA ploidy DNA index distant metastasis surrounding tissue invasion sex duration and tumor cell differentiation. These data suggest that DNA folw cytometry analysis alone, may not provide a sueful biologic basis for the variable prognosis seen with esophageal tumors. PMID- 1296033 TI - [The functional assessment of chronic pain patients activity of daily living and psychosocial disability]. AB - The purpose of this study was to investigate the impact of activity of daily living and psychosocial function in patients with chronic nonmalignant pain. From Jun. 1989 to Nov. 1989, one hundred and eleven cases were assessed by Sickness Impact Profile (SIP) and Taita Symptom Check List (TSCL) to evaluate the disabilities associated with chronic pain. Patients showed significant impairment in the functions of physical psychosocial work and recreational activities. It was also apparent that the psychosocial disabilities were more severe than physical disabilities. Specifically, they showed anxiety depression and significant somatization. Analysis by stepwise multiple regression indicates that sex age educational level employment status diagnosis and pain intensity were the significant influencing factors related to the disabilities of activity of daily living and psychosocial function. The results supported the validity of the SIP as a measurement of functional status with chronic pain patients. Specifically, the psychosocial dimension was significantly correlated with the psychological and psychosocial distress categories of the TSCL. Based upon its reliability validity breadth of assessment and ease of administration, the SIP appeared to be well suited for the assessment of patients with chronic pain and for evaluating the efficacy of multidisciplinary pain treatment. PMID- 1296034 TI - Congenital absence of the pulmonary valve: report of two cases with review of the literature. AB - Congenital absence of the pulmonary valve is an uncommon combination of anomalies. Recently, we encountered two such cases, one associated with tetralogy of Fallot (case 1), the other with ventricular septal defect (case 2). Clinically, our cases had minimum symptoms. The congenital cardiac anomalies were diagnosed with physical examination, chest x-ray film, echocardiography, and confirmed with cineangiography. These procedures disclosed a rudimentary pulmonary valve, pulmonary regurgitation and aneurysmal dilatation of the main and right pulmonary artery. In case 2, the right lower pulmonary artery occlusion and left hydronephrosis were also demonstrated by magnetic resonance imaging. The two cases underwent surgical repair to correct the tetralogy of Fallot and the ventricular septal defect respectively. Our experience in diagnosing these cardiac anomalies is reported. PMID- 1296035 TI - [Clinical and scanning electron microscopic studies on Norwegian scabies infection]. AB - Two typical cases of Norwegian scabies were studied clinically, scanning electron microscopically and histopathologically. Case 1 was a boy with Down's syndrome and case 2 was a man with adult T cell leukemia/lymphoma. Their clinical pictures showed hyperkeratotic plaques and warty crusts on hands, feet, ears, elbows and buttocks. Direct examination of the KOH preparation revealed many embryonated sarcoptic eggs, postpartum egg-shells, fecal pellets, larvae and male and female adult mites. Histopathologic examination showed several burrows inside the thick horny layer. Many sarcoptic egg-shells, mites and fecal pellets were found in the burrows. Psoriasiform hyperplasia and parakeratosis were noted, too. The size and shape of the sarcoptic eggs and the detailed structure of mites and molt were observed by using a scanning electron microscope. Besides, hook-like structures were noted at the tarsi of both forelegs and hindlegs. We suggest that the larvae crawl out from longitudinal openings in the egg-shell by the use of hook-like structures. The mites also used these hook-like structures to make the burrows. Scanning electron microscopy provides a good method to understand the dynamics of these burrowing parasites. It is helpful in illustrating the behavior of the scabies mites in their burrows in Norwegian scabies patients. PMID- 1296036 TI - [Ileal inflammatory fibroid polyp: case report]. AB - The inflammatory fibroid polyp is a rare, polypoid lesion in the gastrointestinal tract. It occurs in the stomach, small intestine, and large intestine in descending order of frequency. This case report shows an ileal inflammatory fibroid polyp that causes ileoileal intussusception. So far, the histogenesis and pathogenesis of these kinds of polyps are still uncertain. Under the microscopic examination, the lesion appears to be made up of spindle-shaped or stellate cells that are morphologically identical to proliferating fibroblasts. Immunostaining results are strongly positive for vimentin and focally positive for S100 protein. However, epithelial membrane antigen, factor VIII R Ag, smooth muscle actin, and lysozyme test are all negative. This favors the view that the inflammatory fibroid polyp is fibroblastic in origin. PMID- 1296037 TI - The serum ferrokinetics in Parkinson's disease. AB - Ferrous ion is an essential cofactor in dopamine synthesis and its decrease may reduce the dopamine production in the nigrostriatal system, the basis of pathogenetic mechanism in Parkinson's disease (PD). Therefore, parkinsonians may have an abnormal systemic ferrokinetics. The serum iron, ferritin, total-iron binding-capacity (TIBC) levels and transferrin saturation were analysed in 15 patients with Parkinson's disease and 30 controls. The serum iron was lower in PD (95.53 +/- 33.5 micrograms/dl) than in controls (102.5 +/- 32.5 micrograms/dl), but the difference was statistically nonsignificant. The ferritin, TIBC and transferrin saturation were also similar in both groups. The systemic ferrokinetics in our PD was normal, but the ferrokinetics between the central and systemic compartments was different in PD. Therefore, reduction of central dopamine in PD is unlikely due to hypoferruginemia. PMID- 1296038 TI - A comparative study with intracavernous injection of prostaglandin E1 versus papaverine for the diagnostic assessment of erectile impotence. AB - The intracavernous injection of vasoactive drugs is a valuable diagnostic aid and an important tool for the treatment of erectile failure. A comparative study with intracavernous injection of prostaglandin E1 (PGE1) and papaverine was performed in 60 patients with impotence. We evaluated the efficiency and side effects of both agents. The overall positive response rate was 85.0% in the PGE1 group and 65.0% in the papaverine group which suggests PGE1 has a stronger vascular effect. The mean onset of maximal erection was after 9.6 minutes in the PGE1 group and after 6.5 minutes in the papaverine group. The mean maintenance of erection was for 53.2 minutes in the PGE1 group and for 38.6 minutes in the papaverine group. There were no systemic side effects of either agent. Three instances of injection pain and 2 of burning sensation in the penis were noted in the PGE1 group, while in the papaverine group, there were 21 reports of injection pain, 4 of prolonged erection and 2 of burning sensation in the penis. These results suggest that PGE1 is a more desirable vasoactive alternative for the diagnosis of impotence. PMID- 1296039 TI - Cystic intracranial meningioma. AB - Between April 1983 and April 1991, we studied nine cases of intracranial meningioma with cystic change out of 100 intracranial meningioma patients. The incidence was 9%. The patient's ages ranged from 40 years to 75 years old. There were five men and four women, of them, three had intratumoral cysts, and six had peritumoral cysts. Histologically, 7 cases were diagnosed as meningothelimatous type, one as psammomatous and the other one as angioblastic type. All the tumors with cystic change in this series were greater than two centimeters in diameter. Because the morphology was indistinct, Nauta's type II cystic meningioma was easily misdiagnosed as glioma or metastatic tumors preoperatively. Microsurgery is the best way for complete removal of the cyst wall to prevent recurrence. PMID- 1296040 TI - [The strength and functional performance of patients with Duchenne muscular dystrophy based on natural history]. AB - Duchenne muscular dystrophy (DMD) is a disease of progressive muscular weakness and wasting. This study is designed to evaluate the muscle strength and functional performance of patients with DMD during the natural progression of this disease. This study comprises a sample of 35 subjects who were confirmed to have DMD. Manual muscle testing (MMT) was used to evaluate muscle strength, the Brooke functional scale to rate the motor function of the upper extremity, and the Vignos functional scale to rate the motor function of the lower limbs. The results showed a significant positive correlation between age and the decrement in strength, i.e. a one year increment in age led to a 3.9% decrease in the average muscle strength. The strength loss always occurred in a typical pattern proceeding from the lower extremities to the upper extremities, and from the proximal to the distal parts. There was a significant negative correlation between muscle strength and both the Brooke and Vignos functional scales. These findings may suggest that decreased muscle strength results in a progressive worsening of the functional performance of the extremities. In addition, the Brooke scale is significantly correlated with the Vignos scale through the natural course of DMD. The high percentage (90.5%) of subjects without the long leg braces needed for ambulation indicates an inadequate rehabilitation care for DMD patients in this country. PMID- 1296041 TI - [Dipyridamole Tc-99m MIBI myocardial perfusion scintigraphy in patients with post infarction chest pain symptom]. AB - To evaluate the efficacy of stress Tc-99m MIBI myocardial perfusion imaging using intravenous dipyridamole in detecting coronary artery disease (CAD) and to determine if chest pain symptom is a proper index for detection of myocardial ischemia in post-infarction patients, we observed 73 cases (65 men, 8 women, 38 79 years old) between Sept. 1990 and May 1992. All patients were suffered from old myocardial infarction (MI) evidenced by history and ECG and were divided into two groups: group I involving 41 patients with post-infarction chest pain symptom and group II including 32 patients without post-infarction chest pain symptom. Among them, 19 (group IA) of group I and 11 (group IIA) of group II received coronary arteriography (CAG) for comparison. Of the 41 group I post-infarction chest pain patients, 17 suffered from old anterior or antero-septal wall (AW) MI, 21 from old inferior wall (IW) MI, 1 from old lateral wall (LW) MI and 2 from combined old AW and IW (AIW) MI by ECG. All 17 patients with AWMI suffered from AW perfusion defect (7 were MI, 10 were MI with ischemia) but 7 of them from multivessel disease (MVD) by Tc-99m MIBI. All 21 patients with IWMI suffered from IW perfusion defect (9 were MI, 12 were MI with ischemia) but 13 of them from MVD by Tc-99m MIBI. Of the patient with LWMI and 2 patients with AIWMI suffered from MVD by Tc-99m MIBI. Of the 32 group II post-infarction patients without chest pain symptom, 12 suffered from old AWMI, 14 from old IWMI, 2 from old LWMI, 3 from AIWMI and 1 from ALWMI by ECG. Of the 12 patients with AWMI, 11 suffered from AW perfusion defect (6 were MI, 5 were MI with ischemia) but 1 of them from MVD by TC-99m MIBI. All 14 patients with IWMI suffered from IW perfusion defect (12 were MI, 2 were MI with ischemia) but 4 of them from MVD by Tc-99m MIBI. Of the 2 patients with LWMI suffered from LW infarction by Tc-99m MIBI. Of the 3 patients with AIWMI and 1 with ALWMI suffered from MVD by Tc-99m MIBI. Of the 11 patients in group IA and 5 patients in group IIA with AWMI, CAG revealed the incidence of infarct-related recanalization of LAD was 9/11(82%) and 4/5(80%) respectively and the respective incidence of MVD was 6/11(55%) and 0/5(0%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296042 TI - [Muscle histochemical changes in rats swimming under high temperature]. AB - The aim of this study was to investigate the effects on muscle tissues of increasing amounts of exercise under normal and high temperatures. An experimental swimming test was applied to completely exercised rats. There were 42 adult male rats divided into 4 groups, including normal control rats, rats which swam to death under room or high temperature conditions, and rats swimming under high temperatures. Immediately after the exercise, the soleus (SOL) and extensor digitorum longus (EDL) muscles were removed by surgical excision. All specimens were frozen in isopentane cooled to -70 degrees C in liquid nitrogen. Cryostat cross sections were cut and stained using histologic and histochemical staining methods to observe pathological changes. The major changes included interstitial edema, muscle fiber atrophy, muscle fiber necrosis, hypercontracted fibers, and ragged red fibers. The rats exercised to death under high temperatures had more apparent changes than those not exercised to death. These results indicate that pathological changes in muscle will be brought about by increasing the amount of exercise and environmental temperature. Since there are more fast twitch fibers in the EDL than in the soleus, pathological changes in muscle tissues are more severe in the EDL. PMID- 1296043 TI - A simultaneous bilateral attack of infectious corneal ulcers in an extended-wear soft contact lens wearer: a case report. AB - A case study was made of a 23-year-old female with simultaneous bilateral infectious corneal ulcers related to extended-wear soft contact lenses. Cultures revealed Pseudomonas aeruginosa and Acinetobacter calcoaceticus. Multiple high risk factors were combined, including extended-wear, poor lens care, bilateral alternate wearing, and smoking. Amphetamine addiction may also have played a role. After treatment, a visual acuity of 20/20 was achieved in both eyes by the use of rigid gas-permeable contact lenses. PMID- 1296044 TI - Structure modification and biological activity of some griseofulvin derivatives. AB - Griseofulvin is an orally acting anti-fungal antibiotic with very limited water solubility. Five chemical modifications were made on the griseofulvin structure in order to evaluate these changes on the antifungal and water solubility properties. Antifungal activity was measured against Tricophyton mentagrophytes, T. rubrum, T. terrestre, and Microsporum canis. The oxime of griseofulvin was the most potent of the five compounds tested, but it was only of equal or less potency than griseofulvin. The somewhat increased water solubility of some of these compounds was offset by the lower anti-fungal potency of the structural modification. PMID- 1296045 TI - Flow cytometric DNA analysis of pleural effusions. AB - A total of 71 cases of pleural effusion in patients with and without cancer were analyzed by conventional cytology and flow cytometry (FCM) in order to detect cells with an abnormal DNA content (aneuploidy). For cytologic examination, the samples were prepared using standard techniques. Sample for FCM analysis were centrifuged and exposed to hypotonic solution containing detergent and propidium iodide. Thirty-eight patients had pleural effusion due to benign disease, whilst 33 patients had primary lung cancer. All 38 patients with benign pleural effusions showed FCM diploidy. There were 17 aneuploidy (52%) and 16 diploidy (48%) in the 33 patients with lung cancer by FCM analysis. Four of these 33 effusions were cytologically negative, however, FCM showed aneuploidy in 2 of these 4 patients. Based on these results, FCM analysis combined with conventional cytopathology yielded 100% specificity, 94% sensitivity and 100% predictive value of positive result. There were no false-positive results but 2 false-negative results. These findings suggest that FCM is a rapid and useful technique in the analysis of pleural effusion and can be a very useful adjunct to conventional cytopathology. PMID- 1296046 TI - Influence of central obesity and obesity level on the prevalence of NIDDM and impaired glucose tolerance. AB - The purpose of this study was to determine the association of the prevalence of non-insulin-dependent diabetes (NIDDM) with central obesity, obesity, and family history of diabetes. This survey consisted of 1590 subjects (646 men, 944 women) aged 30 years or more from the Sun-Ming district of Kaoshiung city. Glucose tolerance status was ascertained by both medical history and a 75-g oral glucose tolerance test according to World Health Organization criteria. In men and women with central obesity (WHR > or = 0.92 in men and > or = 0.85 in women) or obesity (BMI > or = 27.6 kg/m2 in men and > or = 28.3 kg/m2 in women) (WHR: waist-hip ratio; BMI: body mass index), the prevalence of impaired glucose tolerance (IGT) and diabetes was significantly higher, except the prevalence of diabetes in both sexes with obesity and the prevalence of IGT in women with central obesity were not statistically different, as compared with nonobese subjects. The prevalence of diabetes in men significantly increased from the first quartile to the fourth quartile of BMI and the waist-hip ratio (WHR) (4.48% to 9.21% in BMI, 3.67% to 13.61% in WHR), while the prevalence in women also significantly increased from the first to fourth quartile (2.45% to 11.76% in BMI, 2.04% to 13.49% in WHR). Multiple logistic regression analyses revealed similar increase in the prevalence of diabetes among both men and women for every 1 kg/m2 increase in BMI and every 0.05 increase in WHR (1.07-fold and 1.09-fold in BMI, 1.34-fold and 1.32-fold in WHR, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296047 TI - An analysis of brain tumors in south Taiwan. AB - A series of 544 pathologically verified brain tumors were analyzed for the relative incidence and location of tumors as well as the distribution of age and sex. These data were compared to series from north Taiwan, mainland China, America, Germany, and Japan. The incidence of gliomas among brain tumors in south Taiwan (25.4%) was lower than other reports (31-44%). It is interesting to note that the incidence of gliomas in Asian reports is lower than those in America and Germany. A much higher percentage of meningiomas and pituitary adenomas were seen in Taiwan's reports than in those from other countries. Aggressive surgical decompression of brain metastases in selected cases is advised and they comprised 15.1% of total brain tumors operated on. The incidence of brain tumors in the older age group in south Taiwan (22.1%) was much higher than those reported from mainland China (1.65%). Our series revealed a preponderance of tumors in females over males, which may be affected by the greater number of female-predominate meningiomas and pituitary adenomas. PMID- 1296048 TI - [A dental anthropological study of Chinese in Taiwan (3). Dental trait]. AB - Models of the upper and lower dental arches of 125 Chinese children in Taiwan with acceptable normal permanent dentition were surveyed in order to understand the developmental grades of dental traits from the viewpoint of dental anthropology. Developmental grades of dental traits were classified, calculated, statistically analysed by x2 test and results were summarized. Upper anterior teeth showed high frequency of shovel form; upper lateral incisors showed less tendency of regression. Interstitial cusp, lingual cusp, paracusp, central prominence and occlusal groove of lower premolars developed prominently. Upper molars showed low frequency of Carabelli cusps. Hypocone of upper second molars showed strong tendency of regression, but metacone had low regression tendency and a strong degree of compression. Compared to Japanese, Central American and South American Indians and Caucasians, the development of dental traits of Chinese in Taiwan was more similar to that of Japanese than to others. The characteristics of dental trait of Chinese in Taiwan and Japanese also showed greater similarity to Central and South American Indians than to Caucasians. PMID- 1296050 TI - [Aicardi syndrome: a case report]. AB - A 5-year-old girl had suffered from infantile spasms since 3 months of age. Cranial computerized tomography revealed agenesis of the corpus callosum. Abnormal ocular fundus features consisted of bilateral disc colobomas and lacunar pigment change in her right eye. The clinical presentations were consistent with Aicardi syndrome. The ophthalmologic manifestations of Aicardi syndrome will be discussed in this paper. PMID- 1296049 TI - [A survey of the relationships between children and their parents in chronic disease risk factors, health knowledge and lifestyles]. AB - The purpose of this study is to understand the relationships for risk factors, health knowledge and lifestyles between children and their parents. 2806 primary schoolchildren in Kaohsiung City were measured for selected risk factors: serum cholesterol (CHOL), triglyceride (TG), systolic and diastolic blood pressure and height and weight for obese index (Rohrer's index). Children whose Rohrer's index > or = 150, or blood pressure, or CHOL, or TG level were above the 95th percentile distribution in the same age group were categorized as the risk group, the other children fell into the non-risk group. Using random sampling, 180 children were chosen from risk group and non-risk group respectively. A structured questionnaire about health knowledge and lifestyles were filled out by these children and their parents. In the risk group, the questionnaire was completed by 157 children, 103 fathers and 112 mothers. In the non-risk group, 102 children, 83 fathers and 82 mothers completed the questionnaire. The same risk factors examination of children was given to parents; 86 fathers and 144 mothers completed the examination from the risk group, while 56 fathers and 98 mothers completed the examination in the non-risk group. The results showed that: (1) there were significant positive correlations between children and their parents in CHOL, TG and obese index in risk group; children of mothers with higher CHOL and TG levels also showed higher CHOL and TG levels, (2) childrens' health knowledge was not correlated with parents' health knowledge, (3) childrens' lifestyles showed a significant positive correlation with mothers' lifestyles, (4) health knowledge has a significant positive correlation with childrens' and parents' lifestyles, (5) healthy lifestyles have a negative correlation with Rohrer's index in children and a negative correlation with TG level in fathers. The results suggest the presence of certain relationships for risk factors and lifestyles between children and their parents. PMID- 1296051 TI - [Surgical treatment of biliary cyst]. AB - The experience with surgical treatment of 21 patients with a biliary cyst who underwent 25 operations has been analysed. The authors came to a conclusion about unexpediency to use the walls of a cyst in creation of the cystodigestive anastomosis. The operations with complete removal of the cystic wall are recommended. PMID- 1296052 TI - [Differential treatment of focal traumatic brain injury]. AB - On the basis of observation of 65 patients with focal traumatic injury to the brain (hematoma of mater encephali was noted in 24, intracerebral--in 27, a focus of type III brain contusion--in 24, type IV--in 11, multiple hematomas and foci on contusion-crush--in 21), the criteria for their non-surgical treatment have been substantiated. Choice of a method for the treatment depends on the sizes of a hematoma, focus of contusion-crush, location of an injury, degree of its influence on the brain structures (deformation, shift), value of intracerebral pressure, dynamics of the clinico-roentgenologic symptoms. PMID- 1296053 TI - [Staged treatment of patients with lymphedema of the lower extremities]. AB - At examination of 120 patients with lymphedema of the lower extremities, in 70% of them, structure and function of lymphangion were preserved. State of lymphangion is of great importance in substantiation of the tactics of treatment. In preserved morphofunctional properties of lymphangion, the operation of lymphovenous shunting is effective in 83% of the patients. Stimulation of contractile activity of the lymphatic vessels at the stages of in-patient, out patient treatment and that in sanatoria and health resorts contributes to improvement of a result of treatment of the patients. PMID- 1296055 TI - [Methods for surgical prophylaxis of the development of acute gastroduodenal ulcers]. AB - The results of the use of prolonged novocaine blockade with the aim of prevention of the development of acute gastroduodenal ulcers in 57 patients are presented. In 21 case, the prolonged blockade of the vagus nerves was used, in 36--that of the ligamentum teres hepatis. After the operation, the proteolytic activity and acidity of gastric juice were studied. All the patients underwent gastroduodenofibroscopy with biopsy and target pH-metry. Under the influence of novocaine blockade, the proteolytic activity decreased, pH increased. At endoscopy, no acute erosive-ulcerous lesion of mucosa was revealed. Thus, a high effectiveness of the use of prolonged novocaine blockade has been proved. PMID- 1296054 TI - [Venous occlusive plethysmography in assessment of hemodynamics in arterial thrombosis of the lower extremities]. AB - With the use of a method of venous occlusive plethysmography changes, in regional arterial and venous hemodynamics in 75 patients with arterial thrombosis as well as in 47 after reconstructive intervention at the immediate period, and in 25--at the late period were studied. It was established that in ischemia progression, the volume blood flow rate at rest and maximum rate decreased, indicating severe impairement in reserve possibilities of blood flow, maximum venous outflow reduced, venous filling of the vessels increased. In thrombosis, rough disorders in reserve possibilities of blood flow in the aorto-iliac segment were noted. After operation, dynamics of the indices didn't depend on type of reconstructive intervention and was determined only by adequacy of blood flow restoration in the extremity. PMID- 1296056 TI - [Lipid peroxidation and impairement in erythrocytic properties in patients with ulcer disease before and after surgery]. AB - The state of peroxide oxidation of lipids (POL) in the erythrocytes before and after the operation was studied. In patients with ulcer disease, the correlation between POL activity and changes in erythrocytic properties was noted. At the period of disease exacerbation, activation of POL processes in erythrocytes, suppression of the antioxidation protection (AOP), impairement in hemorheologic indices (increase in aggregation of erythrocytes, their resistance to acid hemolysis, reduction in their capacity for deformation) were revealed. Pronouncement of the pathologic changes after the operation depended on a background state of POL and AOP. In ulcer disease, the impairment in POL/AOP balance caused the development of postoperative complications. To prevent the development of complications, the administration of antioxidants is expedient. PMID- 1296057 TI - [The effect of smoking on the long-term outcome of closure of perforated gastric and duodenal ulcer]. AB - Examined were 164 patients at the long-term period after closure of a perforative ulcer of the stomach and duodenum. The negative effect of smoking on acid production and protective barrier of gastroduodenal mucosa leading to worsened healing of an ulcer closed and its recurrence in 50% of the patients operated on has been established. It was noted that in smokers, irrespective of a number of the cigarettes being smoked, an excellent and good long-term result was observed 2.5 times less often, and a poor one--3 times more often than in non-smokers. PMID- 1296058 TI - [Method of intraoperative hemostasis in parenchymatous hemorrhage]. AB - The authors have developed a new method for intraoperative hemostasis in parenchymatous hemorrhage. Hemostasis is achieved by means of electrophoresis of fibrinogen and some other factors of blood coagulation into the organ parenchyma. Approbation of the method on dogs has demonstrated its atraumaticity and safety. PMID- 1296059 TI - [Cystic duct obstruction in the pathogenesis of acute experimental cholecystitis]. AB - The experimental model of acute cholecystitis with a regulated cuff, which permits to reproduce the state of bile outflow in patients with acute inflammation of the gallbladder, when the cystic duct is partially, or completely obturated, has been developed. The results of investigation can contribute to choice of surgical tactics in acute cholecystitis. PMID- 1296060 TI - [Treatment of external pancreatic fistula]. AB - In the clinic, 56 patients with an external pancreatic fistula was treated. After conservative treatment, a fistula closed in 43 patients, and was functioning in 13. Fistuloenterostomy was performed in 6 patients, resection of the left lobe of the pancreas--in 7. There were no complications and lethal outcomes. The method for return of the pancreatic juice into the duodenum has been suggested. PMID- 1296061 TI - [Diagnostic accuracy in acute pancreatitis in the prehospital and early hospital stages]. AB - The results of the analysis of diagnosis of acute pancreatitis on the basis of studying 3634 case records are presented. Errors in the diagnosis of acute pancreatitis at the prehospital stage were established in 61.9%, at the early hospital stage--in 32.35% of cases, usually in the form of hyperdiagnosis of the disease. PMID- 1296062 TI - [Repeated surgeries of the bile ducts]. AB - The results of examination and operative treatment, of 74 patients with the postcholecystectomic syndrome, who underwent 81 restorative and reconstructive operation 1 month to 21 year after cholecystectomy, have been summarized. The postoperative lethality was 8%. Peritonitis and hepatic failure were the main causes of death. Necessity of early performance of a reoperation has been substantiated. PMID- 1296063 TI - [Choice of operative intervention in the treatment of echinococcosis of the left hepatic lobe]. AB - The results of treatment of echinococcosis of the left hepatic lobe in 15 patients have been analysed. Resection of the left hepatic lobe is considered an operation of choice in presence of a large cyst. PMID- 1296064 TI - [Informative value of amino acid reserve in the blood plasma in cholestatic and septic syndrome]. AB - Syndrome of cholestasis is characterized by pronounced increase in concentration of the sulphur containing, ketogenic amino acids and intermediates of a cycle of urea formation in the blood plasma; sepsis--by decrease in pool of glycogenic amino acids, increase in concentration of free ammonium and reduction in correlation of amino acid concentration with branched hydrocarbon chain of aromatic amino acids. In cholestasis, the levels of ammonium alpha-amino butyrate and aromatic amino acids were the most informative indices, in sepsis--content of lysin, glutamate, cystein and cysteate. PMID- 1296065 TI - [Use of absorbable antimicrobial suture material at the gastroenteric anastomosis in patients with gastric and duodenal disease]. AB - The authors in creation of the internal layer of sutures of gastroenteric anastomoses in 80 patients have used the synthetic antimicrobial absorbable material. No complications related to use of the suture material were revealed. The results obtained permit to recommend the new suture material for more wide use in the gastrointestinal surgery. PMID- 1296066 TI - [Computerized tomographic semiotics of acute pancreatitis]. AB - In the article, the expediency of the use of computerized tomography in the diagnosis of the different forms of acute pancreatitis in 49 patients is substantiated and results are analysed. PMID- 1296067 TI - [New approaches in diagnosis and therapy of the thoracic outlet syndrome]. AB - The results of diagnosis and treatment of the thoracic outlet syndrome (TOS) in 35 patients have been analysed. Compression of the subclavicular neurovascular bundle at the site of its outlet from the thoracic cavity was most frequent cause of TOS development. A degree of compression was assessed quantitatively by the data of a modified functional dynamic test. The modified operation, including resection of the I rib (and of a cervical one in its presence), scalene muscle, musculus pectoralis minor, periarterial sympathectomy of the subclavicular artery, was performed. In narrow (less than 1.5 cm) costoclavicular space, the II rib was additionally resected. An excellent long-term result is indicative of the effectiveness of the method. PMID- 1296068 TI - [Radiodiagnosis of the thoracic outlet syndrome]. AB - The results of roentgenological investigations in thoracic outlet syndrome are summarized. The method for defining the width of a costoclavicular cleft and its diagnostic importance in 72 patients operated on is described. A role of anomalies of the osteofibrous formations in the development of neurovascular compression is noted. PMID- 1296069 TI - [Surgical treatment of non-specific aortoarteritis of the aorto-femoral segment]. AB - For 15 years, the authors observed 158 patients with non-specific aortoarteritis. Of them in 37 (23.4%), isolated lesion of the terminal aorta, iliac and femoral arteries was revealed; in 81.1%--severe degree of ischemia of the lower extremities, 39.4% of men had impotency. Associated lesions of the aorta and arteries of the lower extremities was revealed in patients with acute inflammatory process. The extent of vascular occlusion depended on its presence. Surgical treatment was performed in 35 patients; in 30, the reconstructive operations were performed, in 3--lumbar sympathectomy, in 2--amputation of an extremity. At the early postoperative period, a good result has been noted in 82.9%, 5.7% of patients died. Twenty six patients were followed up for 5 years, 60.1% of them have shown a good result. PMID- 1296070 TI - [Clinical aspects and examination of obliterative atherosclerosis of the major arteries of the lower extremities]. PMID- 1296071 TI - [Pathogenesis of hemorrhage from esophageal varices]. PMID- 1296072 TI - [Colonic necrosis as a complication of acute pancreatitis]. PMID- 1296073 TI - [The role of opioids in the osmotically stimulated secretion of vasopressin. Report 2. Results of investigations (lecture-review)]. PMID- 1296074 TI - [Pathogenesis and methods of surgical treatment in disseminated forms of pancreonecrosis]. PMID- 1296076 TI - [Pancreatic cyst simulating a cyst of the left kidney]. PMID- 1296075 TI - [Errors in the diagnosis of posttraumatic splenic pseudocyst]. PMID- 1296077 TI - [Difficulties in the diagnosis of a duplicated gallbladder in acute cholecystitis]. PMID- 1296078 TI - [Ascariasis as a cause of hepatic colic]. PMID- 1296079 TI - [Level of circulating immune complexes in patients with complicated cholelithiasis]. AB - In 165 patients with the different forms of cholelithiasis, a level of the circulating immune complexes (CIC) was measured in the blood serum and bile from the common bile duct at the postoperative period. In associated purulent resorptive and cholemic intoxication, the CIC level in the blood serum and bile increases. This, in turns, enhances the likelihood of the development of purulent septic complications at the postoperative period, and requires performance of target immunocorrection. PMID- 1296080 TI - [A spiral-like drain for external drainage of the extrahepatic bile ducts]. PMID- 1296081 TI - [A methods for suturing the gallbladder bed after cholecystectomy]. PMID- 1296082 TI - [A method for upper median laparotomy]. PMID- 1296083 TI - [Acute destructive appendicitis associated with destructive cholecystitis]. PMID- 1296084 TI - [Gastric phlegmon associated with acute pancreatitis and chronic calculous cholecystitis]. PMID- 1296085 TI - [Surgical methods in the treatment of non-formed pancreatic cyst in patients with acute pancreatitis]. PMID- 1296086 TI - [Pyogenic hepatic abscess developing after perforation of the stomach by a fish bone]. PMID- 1296087 TI - [Isolated subserous rupture of the gallbladder]. PMID- 1296088 TI - [Traumatic two-stage rupture of the main spleen in the presence of accessory spleen]. PMID- 1296089 TI - [Value of exhaled air acetone level in assessing the impairement of secretory pancreatic function in acute destructive pancreatitis]. AB - For the first time, a semiconductor gas sensor of original construction was employed to measure acetone level in the biologic liquids and gases in patients with acute destructive pancreatitis. A statistically significant difference in acetone level in the exhaled air of the healthy subjects, patients with edematous and destructive forms of acute pancreatitis and diabetes mellitus has been established. PMID- 1296091 TI - Synonymous codon preferences in bacteriophage T4: a distinctive use of transfer RNAs from T4 and from its host Escherichia coli. AB - Codon usage data of bacteriophage T4 genes were compiled and synonymous codon preferences were investigated in comparison with tRNA availabilities in an infected cell. Since the genome of T4 is highly AT rich and its codon usage pattern is significantly different from that of its host Escherichia coli, certain codons of T4 genes need to be translated by appropriate host transfer RNAs present in minor amounts. To avoid this predicament, T4 phage seems to direct the synthesis of its own tRNA molecules and these phage tRNAs are suggested to supplement the host tRNA population with isoacceptors that are normally present in minor amounts. A positive correlation was found in that the frequency of E. coli optimal codons in T4 genes increases as the number of protein monomers per phage particle increases. A negative correlation was also found between the number of protein monomers per phage and the frequency of "T4 optimal codons", which are defined as those codons that are efficiently recognized by T4 tRNAs. From these observations it was proposed that tRNAs from the host are predominantly used for translation of highly expressed T4 genes while tRNAs from T4 tend to be used for translation of weakly expressed T4 genes. This distinctive tRNA-usage in T4 may be an optimization of translational efficiency, and an adjustment of T4-encoded tRNAs to the synonymous codon preferences, which are largely influenced by the high genomic AT-content, would have occurred during evolution. PMID- 1296090 TI - The effect of auxiliary conditions on intestinal unstirred layer diffusion modelled by numerical simulation. AB - Estimation of intestinal unstirred layer thickness usually involves inducing transmural potential difference changes by altering the content of the solution used to perfuse the small intestine. Osmotically active solutes, such as mannitol, when added to the luminal solution diffuse across the unstirred water layer (UWL) and induce osmotically dependent changes in potential difference. As an alternative procedure, the sodium ion in the luminal fluid can be replaced by another ion. As the sodium ion diffuses out of the UWL, the change in concentration next to the intestinal membrane alters the transmural potential difference. In both cases, UWL thickness is calculated from the time course of the potential difference changes, using a solution to the diffusion equation. The diffusion equation solution which allows the calculation of intestinal unstirred layer thickness was examined by simulation, using the method of numerical solutions. This process readily allows examination of the time course of diffusion under various imposed circumstances. The existing model for diffusion across the unstirred layer is based on auxiliary conditions which are unlikely to be fulfilled in the same intestine. The present simulation additionally incorporated the effects of membrane permeability, fluid absorption and less than instantaneous bulk phase concentration change. Simulation indicated that changes within the physiologically relevant range in the chosen auxiliary conditions (with the real unstirred layer length kept constant) can alter estimates of the apparent half-time. Consequently, changes in parameters unassociated with the unstirred layer would be misconstrued as alterations in unstirred layer thickness. PMID- 1296092 TI - Probability of occurrence of specific oligomers. AB - We improved an already existing formula for calculating the probability of occurrence of specific oligomers (Grob & Stuber, 1987) by taking into account unequal base distribution. This method identifies specific oligomers in a given sequence as candidates for biological signals. PMID- 1296093 TI - Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study. AB - The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296095 TI - Spatial patterns of cells in dividing epithelia. AB - The spatial patterns of cell boundaries in a view of the apical surface of a dividing epithelium are explored by constructing a hypothetical cell pattern of an epithelium of dividing cells. The two elements specified in the hypothetical pattern are the orientation of division planes and the separation between the division planes in neighbouring cells. The orientations of division planes in one generation are all the same but are orthogonal to those in the preceding generation. The division-plane orientations follow in an orthogonal succession, as happens in early embryos. The division planes in neighbouring cells are offset. The contractions of division planes that would occur during cytokinesis distort existing boundaries creating various types of cell shapes. The patterns generated resemble cell patterns found in life. The hypothetical pattern is regenerative and shows how epithelial cell patterns where cells divide might arise. It has enabled the putative identification of sister cells and first cousins in the embryonic chick chorion. PMID- 1296094 TI - Coexistence and competition in HIV infections. AB - In this paper we extend our explanation of a model for the dynamics of the interaction between HIV and the cells of the immune system (Nowak et al., 1990). We show that the Simpson index of viral diversity is a Lyapunov function for a simplified version of this model. We also present a more general mathematical characterization of the nature of the diversity threshold exhibited by the model, including for the first time heterogeneity in parameters like virus replication rate, cytopathicity and antigenicity. The more general diversity threshold condition includes the different contributions of strains with higher replication rates and cytopathicities or strains that are only weakly recognized by the immune system. This leads to some new insights and a more detailed understanding of why the viral diversity falls once the diversity threshold is exceeded. PMID- 1296096 TI - Sensitivity analysis of a new model of carcinogenesis. AB - A new simulation model of carcinogenesis is described which, in addition to the features of a standard clonal two-stage model (loss of both copies of a tumor suppressor gene by point mutations, cell division and cell death), includes a quantitative description of mitotic recombination, DNA repair, and cell to cell interactions in all stages. The model is implemented as a discrete event process. The results of a sensitivity analysis of the model are presented. The most sensitive parameters were found to be: the number of normal cells at risk, and the division rate, death rate and DNA repair efficiency for the intermediate stage cells. Accurate information about these parameters is important for a quantitative understanding of carcinogenesis. The sensitivity of the model to the number of normal cells indicates the importance of understanding the nature of the cells at risk, for example, stem cells vs. differentiated cells. The model can be used to assess the importance of chromosomal damage such as mitotic recombination and epigenetic mechanisms such as hyperplasia and cytotoxicity in the onset of malignant tumors. PMID- 1296097 TI - Comparison of translation in eukaryotic mode with translation in prokaryote mode. PMID- 1296098 TI - Does frequency-dependent selection optimize fitness? AB - In evolutionary biology, the axiom that natural selection tends ideally to maximize inclusive fitness of the individual or some other suitable quantity is often advanced (Cody, 1974; Maynard Smith, 1978; Krebs & McCleery, 1984; Houston et al., 1988). Moreover, the evolutionists generally distinguish two situations (Dawkins, 1980; Maynard Smith, 1982): one in which fitness is independent of the frequency of the phenotypes present in the population (frequency-independent selection), and one in which it does depend on this frequency (frequency dependent selection). This led some authors such as Parker (1984), and more recently Parker & Maynard Smith (1990), to consider "a 2-speed optimization": frequency-independent selection should lead to a "simple optimum" at the end of the selective process, since all the individuals should have the same strategy and the mean fitness of the population should be maximized; frequency-dependent selection, formulated in terms of the theory of games, should lead to a "competitive optimum" even though the "evolutionary stable strategy" (or "ESS"; Maynard Smith & Price, 1973) characterizing the equilibrium "is not the strategy that maximizes fitness in a population sense" (Parker & Maynard Smith, 1990: 30). Our aim in this short communication is to criticize the concept of "competitive optimum" by Parker & Maynard Smith, as well as the general ability of natural selection to "maximize fitness", even in "phenotypic models" (Lloyd, 1977). These models, devoid of genetic constraints since each strategist is assumed to reproduce its own kind, are especially suitable for examining the ideal effect of natural selection. PMID- 1296099 TI - Resource-dependent selection. AB - This paper presents a resource-dependent viability selection differential equation model of continuously reproducing diploid population with two alleles at one locus for a single limiting resource. This model assumes that the genotypic fitness is only a function of the limiting resource. The conditions that the interior equilibrium point of the system exists are that the heterozygote fitness is positive and the homozygote fitness is negative, or the heterozygote fitness is negative and the homozygote fitness is positive at the point. The sufficient and necessary conditions of locally asymptotical stability of the interior equilibrium point are that the heterozygote fitness is positive at the point, or the locally asymptotically stable equilibrium corresponds to the point at which the level of the limiting resource is locally minimized on the zero mean fitness curve, f = 0. PMID- 1296100 TI - Threshold consensus methods for molecular sequences. AB - We introduce a parameterized threshold consensus method (th chi) for molecular sequences which is based on a majority-rule voting principle. In contrast to other frequency-based methods, the th chi method uses a single criterion to return ambiguity codes of different lengths. We derive basic features of the method and establish that it returns at most two ambiguity codes at any position of the consensus sequence. We bound from below the size of the frequency gap that exists when the th chi method returns an ambiguity code. Using such properties, we compare the th chi method to other consensus methods for molecular sequences which are defined in terms of threshold or gap criteria. PMID- 1296101 TI - Phase resetting and fixed-delay stimulation of a simple model of respiratory rhythm generation. AB - In a previous study (Lewis et al., 1990), the response of the respiratory rhythm to a perturbing stimulus was investigated using two different stimulus protocols: phase resetting and fixed-delay stimulation. The first protocol consists of measuring the effects of perturbing an oscillator at different phases of the cycle on the duration of the perturbed cycle. The resulting phase response curves (PRCs) can be used to characterize the properties of the oscillator (Winfree, 1980). A second protocol, fixed-delay stimulation, involves perturbing an oscillator at a fixed latency from the onset of the cycle, repeated every n-th cycle. If a single stimulus produces an effect that lasts longer than a single cycle, complicated responses can be expected from fixed-delay stimulation (Lewis et al., 1987). A simple three-phase model for respiratory rhythm generation based on a hypothesis by Richter and coworkers (1982, 1983, 1986) was investigated in the context of these experimental studies. Phase resetting and fixed-delay stimulation protocols were simulated in the model. PRCs of the model resemble those obtained experimentally: a phase-dependent prolongation or shortening of the inspiratory phase depending on the stimulus magnitude, and a slight prolongation of the expiratory phase. Stimuli delivered to the model repetitively during successive inspiratory periods at a fixed-delay produced various combinations of shortened and prolonged cycles, similar to those observed in the experiments. However, the marked increases in cycle duration observed in the experiments during, as well as after, stimulation were not evident in the model. These comparisons suggest that (1) PRCs may not be an adequate way to evaluate certain models of rhythmogenesis, and (2) to improve the present simplified formulation of the three-phase model of the respiratory oscillator, time-varying stimulus dependent effects should be incorporated. PMID- 1296103 TI - Potential pseudoknots in the PrP-encoding mRNA. PMID- 1296102 TI - Analysis of vagally induced sinus arrhythmias. AB - Vagal stimulation at precise times in successive cardiac cycles can elicit sinus arrhythmias. Two mechanisms have been identified that can, but do not necessarily, cause these vagally induced sinus arrhythmias. First, changes in cycle length elicited by a given concentration of acetylcholine (ACh) depend on the phase of the pacemaker cell action potential when the ACh binds to muscarinic receptors. Second, acetylcholinesterase degrades ACh rapidly enough for the mean concentration of ACh per cardiac cycle to vary from cycle to cycle. We used a mathematical model of the underlying cellular physiology, to examine whether these mechanisms are responsible for arrhythmogenesis. Computer simulation showed that both mechanisms contribute to the vagally induced sinus arrhythmias. PMID- 1296104 TI - [Smoking at work]. PMID- 1296106 TI - [Identification of potential carcinogenic dyes and intermediates on the basis of their genotoxicity]. AB - 41 dyes, pigments and surface-active compounds were tested for mutagenic and genotoxic properties. It was found that 43% of the studied dyes of Polish make which belonged to the azo, triarylmethane and anthraquinone compounds were mutagenic or genotoxic. All the studied pigments and surface active compounds did not reveal potential carcinogenic activity except for NNO Dyspergator whose possible genotoxic activity needs confirmation in further study. PMID- 1296105 TI - [Project for amending regulations regarding jobs prohibited to women]. AB - Considering that the current legal regulations on jobs prohibited to women lack consistency, especially in relation to the criteria for including specific jobs into the prohibited category, and because the regulations fail to protect women satisfactorily from the harmful effects of occupational and environmental loads and exposures, preparation of new legal regulations on those matters has been attempted. Special stress has been put on specifying parameters which, when measured and compared with the suggested allowable values, should provide a basis for deciding whether a woman can be employed at a specified post. Separate criteria have been specified to determine jobs prohibited to women: a) irrespective of age, b) at reproductive age, c) during pregnancy and lactation. The irrespective-of-age restrictions result from lower average physical efficiency of women in relation to men, lower muscular strength and different psychical or biological characteristics. Lower allowable physical loads and lower maximum allowable weights of objects to be carried or moved by women have been specified. In specifying the restrictions for women at the reproductive age it has been assumed that, when determining the maximum allowable concentrations of chemicals at workplaces, effects of those chemicals on the reproducibility and health state of the off spring were taken into consideration. However, for chemicals which, according to the present knowledge, show genotoxic, teratogenic, or reproduction-disturbing effects, employers will be obliged to inform the reproductive-age female employees about the risk involved, as well as to take steps to reduce, as far as possible, below MAC the concentrations of those chemicals in the ambient air at workplaces. The restrictions in the employment of the pregnant and lactating women are intended to ensure conditions enabling correct development of pregnancy and safe growth of the fetus and, subsequently, of the neonate. The restrictions relate to: physical effort--as this has been proved to affect the course and the outcome of pregnancy (increased abortion risk, reduced duration of pregnancy, reduced neonate weight); exposure to carcinogens--as there is evidence that carcinogens display genotoxic properties and are capable of permeating the placenta: exposure to agents which can disturb the course of pregnancy and damage the fetus or unfavourably affect health condition of the offspring even if the MAC and MAI values are not exceeded; exposure to biologic agents, evidently harmful to the fetus and to the condition of health of the progeny.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296107 TI - [Biological evaluation of Indian and Chinese talc aggressiveness]. AB - In order to evaluate biologically the action of two different kinds of talc pulmonary and hemolytic tests were applied and pathomorphological examination carried out on animals. The study was performed on 120 rats within the 6th and 9th months periods. The talcs used in the experiment did not indicate any fibrogenic properties. Morphologic examination did not show any differences in the pathogenetic activity between the Indian and Chinese talcs Inflammatory changes within the lungs and bronchi, pulmonary emphysema and increased levels of fibrosis indices in biochemical examinations have drawn our attention to problems connected with longterm exposure to talc dust. PMID- 1296108 TI - [Effect of carbon disulphide on platelet aggregation in women]. AB - This study was performed in 50 female subjects aged 20-50 years. The women in group II were exposed to 10-14 mg/m3 carbon disulphide. Platelet aggregation was determined according to Born, the concentration of cholesterol and triglycerides with the enzymic method and LDL-cholesterol and HDL-cholesterol by precipitation. It was found that women exposed to CS2 had a significantly higher (p < 0.01) concentration of LDL-Ch. Furthermore, these women demonstrated very active platelet aggregation, reflected mainly by decreased aggregation threshold due to ADP influence. PMID- 1296109 TI - [application of electromyography (EMG) in recognition of lumbo-sacral back pain]. AB - Power spectra of electromyograms (EMG) of back muscles in the lumbo-sacral area were compared in two groups of subjects. In the first one EMGs were registered in 49 young, healthy, males working in standing posture. The recordings were carried out at rest, after application of a 20 kg load and at the onset of pain. In the second group 31 subjects of both sexes and different age, suffering from intense back pain of various etiology, were investigated and compared with a group of 15 healthy persons. In the first group the power level increased after the loading, and in 42 subjects it showed further rise when the pain appeared. In the second group the power level at the range of 25 to 400 Hz, at rest, was significantly higher in the back pain patients than in healthy subjects. The results are discussed from the point of view of their applicability for the diagnosis of back pain. PMID- 1296110 TI - [Activity of selected enzymes in urine of workers from the repair brigades in chemical plants "Organika-Azot" in Jaworz]. AB - In 45 repair service workers of a chemical plant producing pesticides the serum concentration of creatinine and uric acid as well as the concentration of proteins and the activity of alkaline phosphatase, a alanine and aspartate aminotransferases, lactic dehydrogenase, and N-acetyl-beta- glucosaminidase in urine were determined. As compared to 31 healthy controls, the serum creatinine concentration was significantly higher (in any case the creatinine and uric acid concentration did not exceed the upper normal limit), the urine lactic dehydrogenase and N-acetyl-beta- glucosaminidase activity, factored by creatinine, was significantly elevated. The results of the examinations point to a discrete lesion of the kidneys. PMID- 1296111 TI - [Assessment of the degree of air pollution at the work place in coke batteries of polycyclic aromatic hydrocarbons]. AB - The paper discusses the method and results of the assessment of PAHs in airborne particular matter collected at high-level exposure sites in the coke plant. Qualitative analysis of PAHs fraction was made and the content of the most prevalent PAHs was determined. PMID- 1296112 TI - [Musculo-skeletal system diseases in dentists--an analysis of consultation cases referred to the outpatient department of occupational diseases]. AB - During 1984-1991, 188 dentists referred for consultation to the Outpatient Department of Occupational Diseases, Institute of Occupational Medicine in connection with suspected occupational disease of musculo-skeletal system were examined. In total, 122 (64.9%) cases of the occupational diseases were diagnosed, among which chronic inflammation of humeral bone epicondyles (61.5%) and periarticular shoulder inflammation (25.4%) dominated. Claims associated with spondylosis and discopathies were decided to be rejected, as those changes are frequent in the general population and according to the legal regulations currently in force, are not included among occupational diseases resulting from the occupational work. PMID- 1296113 TI - [Prospective examinations concerning the effect of exposure to aromatic hydrocarbons on health status]. AB - The purpose of the study was to evaluate the general and toxicological status of footwear factory workers exposed to toluene, benzene and trace amounts of chromium. The subjects were 80 persons who worked with the glue, and were professionally exposed to aromatic hydrocarbons such as toluene and benzene AT amounts not exceeding the TLVs. The mean age of the subjects was 46.89 years and the mean period of work 20.26 years. Complete internal and neurological examinations were carried out. The following parameters were determined: hematocrit, hemoglobin, erythrocytes, leukocytes, platelets, reticulocytes, chromium, copper, zinc in serum and hippuric acid in urine (in 30 persons). In the examined group no changes in the leukocyte system were found. Two women had a lower hemoglobin level and erythrocyte count. In three persons thrombocytopenia was observed (3.75%). The mean metal levels in serum were within normal values. Only in 4 persons (5.0%) elevated levels of phenol in urine were found which indicated exposure to benzene. In 30 subjects (18 women and 12 men) (most exposed to toluene) the hippuric acid level in urine was examined. It was found to range from 130 mg/l to 2080 mg/l. In the control group not exposed to either of the solvents the level of hippuric acid in urine varied from 190 to 330 mg/l. There was little effect of aromatic hydrocarbons on hematopoiesis. The increased absorption of benzene or toluene found in the examined persons would indicate a necessity for biological monitoring of this group. PMID- 1296114 TI - [Opinions on health status and ability to work of persons with a history of subarachnoid hemorrhage]. AB - This paper is based on the author's own experience obtained during her activities at the Outpatient Department of Occupational Diseases, Institute of Occupational Medicine, Lodz, Poland, as well as on the literature data relating to the methods of evaluating health condition in people with subarachnoid hemorrhage history. Factors affecting prognosis and their effect on the possibility of taking up occupational job have discussed. Jobs contraindicated for people with subarachnoid hemorrhage history have been specified. PMID- 1296115 TI - [Current state of studies on the effect of organic solvents on the nervous system]. AB - Current problems of clinical neurotoxicology, particularly the effect of organic solvents on the nervous system functions have been discussed. A review of the literature on the neurophysiological methods for use in toxicology been presented. Special attention has been paid the usefulness of evoked potential testing for detecting early changes in the nervous system caused by action of neurotoxic chemicals. PMID- 1296116 TI - Measuring infants' temperature. PMID- 1296117 TI - Female genital mutilation--a practice that should have vanished. PMID- 1296119 TI - Perinatal mortality in Scotland. Mabel Liddiard Memorial Lecture. PMID- 1296118 TI - Why midwives should scan. Interview by Mark Cunningham. PMID- 1296120 TI - Grief and loss in childbirth. PMID- 1296121 TI - Artificial rupture of membranes in spontaneous labour at term. PMID- 1296122 TI - Developing research proposals workshop--September 1991. PMID- 1296123 TI - Epidural analgesia for labour (intermittent top-ups or continuous infusion). PMID- 1296124 TI - The second stage of labour--a battle against tradition. PMID- 1296125 TI - Quite a challenge! PMID- 1296126 TI - Committed to caring--committed to change. PMID- 1296127 TI - Health Committee report on the maternity services. PMID- 1296128 TI - "We overcame all". PMID- 1296129 TI - Hard work and persistence. PMID- 1296131 TI - Traditional Chinese medicine in obstetrics. PMID- 1296130 TI - Should mothers know more about breast-feeding? PMID- 1296132 TI - Physical education & the pregnant woman--the way forward. PMID- 1296133 TI - Health for life--yours and theirs. PMID- 1296134 TI - Taking to the water with Manchester's midwives. PMID- 1296135 TI - ENB recognises midwifery as a separate profession. PMID- 1296136 TI - [Lead in the 90's: "new" rules for the "oldest" of environmental toxins?]. AB - Present lead (Pb) exposures in working and general environments are undoubtedly lower than several decades ago so that mean blood lead levels (PbB) in the main industrial sectors using lead, such as ceramics and accumulator manufacturing, are now about 30 micrograms/100 ml and in the general population between 10 and 15 micrograms/100 ml and in some situations decidedly below 10 micrograms/100 ml. At the same time increasingly more accurate and sometimes original knowledge has been acquired on the effects of low-level Pb exposure, especially the effects on the nervous system, the cardiovascular system, the endocrine and immune systems, on heme-containing enzymes, and on the reproductive system. The question of a possible mutagenic and carcinogenic action of Pb is, however, still open. It is also clear that many of the above effects were observed for PbB levels considerably below the current limit levels. For certain effects, like those on heme, the central nervous system, and blood pressure, it has not been possible to establish a threshold below which they will not occur. With effects that are so different in nature and degree and with changed exposure conditions, a critical re-examination of the assumptions on which current knowledge and prevention models are based appeared appropriate. In particular, action models are proposed for discussion which, besides the priority aim of restricting use of Pb to those situations where there is no alternative and to those working environments which guarantee compliance with modern regulations and prevention procedures, have two differentiated objectives: the first is to eliminate the dose-dependent effects occurring at exposures higher than those in the general population; the second is to reduce to the lowest possible level the effects with no threshold or with as yet unestablished threshold, by means of actions in favour not only of occupationally exposed groups but also the general population. PMID- 1296137 TI - [Metabolic polymorphisms and the cancer risk: the evaluation of epidemiological studies]. AB - Genetic modulation of environmental exposures associated with common malignancies is an attractive mechanism to explain differential susceptibility to tobacco or occupation-related carcinogens in the population. The paper reviews the evidence for an association between three genetically based metabolic polymorphisms (N acetyltransferase, Debrisoquine, hydroxylase, aryl hydrocarbon hydroxylase), which have been implicated in the modulation of lung or bladder cancer risks. Fair to good support emerged for both an association of the acetylation phenotype with occupationally related bladder cancer and for an association of the debrisoquine metabolic phenotype with lung cancer, although in neither case was the evidence completely convincing. Epidemiologic evidence for an association between aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of the difficulties in the assay and subsequent confounding factors. PMID- 1296138 TI - Increased lead absorption in children living in an area with high concentration of ceramic workshops. AB - Children who live in contaminated areas or whose cohabitants are occupationally exposed to lead are at a higher risk of lead absorption. The present study examined the blood lead levels of 539 nursery and primary school children living in three towns in the Umbria region (central Italy): Deruta, Corciano and Perugia. Deruta is a small town with a high number of ceramic workshops; Corciano is a mainly agricultural centre; Perugia is the largest town in Umbria. The lead concentrations of house dust, soil, air and water ducts of Deruta and Corciano were also examined. The blood lead levels were significantly increased in children in Deruta (9.7 S.D. = 3.6 micrograms/dL, p < 0.05) and Perugia (9.6 S.D. = 4.0 micrograms/dL, p < 0.05) compared to Corciano (8.3 S.D. = 1.9 micrograms/dL). In Deruta the blood lead levels were higher in children whose cohabitants worked in small ceramic factories or workshops near or in the homes (10.7 S.D. = 4.1 vs 9.0 S.D. = 3.0 micrograms/dL, p < 0.05). The mean concentration of lead in the house dust in Deruta was higher than in Corciano (2.8 S.D. = 2.5 vs 0.8 S.D. = 3.8 micrograms/m2, p < 0.01); the highest values were found in the house dust of the homes of children whose cohabitants worked in small ceramic factories either near or in the same building. There was no significant difference between the concentrations of lead in street dust or tap water of Deruta and Corciano. We conclude that the production of handworked ceramics could lead to an increased risk of lead absorption in children, particularly those who live with workers from this sector. PMID- 1296139 TI - [The efficacy of personal prevention measures in controlling the exposure to metals of welders]. AB - Biological monitoring of welders employed in a power plant showed urinary nickel levels largely exceeding the reference values (Ni-U welders mean = 43.2, S.D. = 22.1 micrograms/24 h; Ni-U reference values mean = 2.7, S.D. = 1.4 micrograms/24 h). Subsequently urinary excretion levels of other metals (Cr, Zn, Fe, Mn, Cu, Al, Pb) were measured for a more complete assessment of occupational exposure of these subjects; only aluminum and lead were found to slightly exceed the reference values and correlate with urinary nickel levels. As a consequence of these results, some adjustments in personal prevention measures were introduced at the workplace; the subsequent biological monitoring checks showed a progressive reduction in urinary nickel excretion levels over time in all welders. PMID- 1296140 TI - [The exposure to tobacco smoke of the employees of a telephone company]. AB - Smoking habits were studied in a group of employees of a telephone company. The smokers were 34% of the subjects interviewed. The non-smokers said that they were bothered by other people smoking everywhere and also to a considerable extent at the workplace. Differences between smokers and non-smokers and between exposed and non-exposed non-smokers were studied by measuring expired CO and urinary cotinine. An expired CO concentration of 10 ppm discriminated between smokers and non-smokers. A mean urinary cotinine concentration of about 16 ng/mg was found in the exposed non-smokers, corresponding to the direct smoking of 1/10 of a cigarette per day. The search for the metabolic phenotype of destromethorphane, which was taken as an indicator of susceptibility to contract lung cancer due to IPA, showed that there were no differences between smokers and non-smokers since the rapid metabolizers, and therefore subjects potentially exposed to risk of lung cancer due to tobacco smoke, prevailed in both groups. PMID- 1296141 TI - [In the search for lost anamneses]. PMID- 1296142 TI - [Important steps toward a definition of the nephrotoxicity of organic solvents]. PMID- 1296143 TI - [Work hygiene and safety in Great Britain]. PMID- 1296144 TI - [The blood calcium error induced by oral calcium loading: study of the homeostatic compensation mechanism]. AB - The oral calcium load test, originally proposed for evaluating the intestinal calcium absorption and the renal calcium leak triggers some endocrine and metabolic responses addressed to correct the "calcemic error" induced by the load. Besides the increased plasma calcium there are: plasma PTH drop, increment in the urinary calcium excretion and in the threshold of tubular phosphate reabsorption. These responses have been measured and reciprocally correlated in 9 young adults at different times after the oral calcium load. The responses can be assessed with high precision in clinical practice and are in agreement with the known physiological models. The oral calcium load test is proposed as a tool for studying in the osteopenic population in the individual's capacity of correcting the calcemic error induced by the load. PMID- 1296145 TI - [Reduction in parathormone secretion after oral calcium loading in osteoporotic adults]. AB - The purpose of this study was to verify if a decreased inhibition of PTH secretion (abnormal suppressibility) in response to physiological increment of plasma calcium is present in patients with osteoporosis. The plasma concentration curve of intact PTH 1-84 following an oral calcium load (Pak) has been calculated in a selected population of 38 osteopenic patients (16 males and 22 females) and in a control group of 9 young healthy adults. All the patients included in this study a) had no past or present diseases and medications of potential influence on calcium homeostasis, b) showed a maximal calcemic response to the oral calcium load equal to that of the control group. PTH suppressibility was significantly smaller in the osteoporotic patients (-42% in males and -32% in females) than in the control group (-76%). This abnormal suppressibility of PTH is independent on sex and, in the females, also on postmenopausal estrogen deficiency. These results support the hypothesis that osteoporosis is associated to an altered secretory response of parathyroid glands maybe due to reduced sensitivity of the parathyroid cells to extracellular calcium. PMID- 1296146 TI - [Microvascular complications in diabetes mellitus. Pathogenetic aspects]. AB - Chronic microvascular complications are important causes of mortality and morbidity in people with diabetes mellitus. After 10 years of disease, nearly 70% of diabetics are affected by retinopathy and about 40% by nephropathy. Genetic factors have a great influence on the development of diabetic microvascular complications, as pointed out by their association with HLA system and Na/Li countertransport, but epidemiological and experimental studies show that the greater role is played by the metabolic milieu. Protein glycation, sorbitol pathway and lipid abnormalities can be responsible for early and fast development of the microvascular complications of diabetes mellitus. PMID- 1296147 TI - [Osteocalcin and hyperthyroidism]. AB - Osteoporosis may be induced by hyperthyroidism through an increase of bone turnover, because bone resorption exceeds formation in this condition. Also therapy with 1-thyroxine, especially by TSH-suppressive doses, may induce a reduction in bone mineral content. Circulating osteocalcin (sBGP) significantly increases both in endogenous and exogenous hyperthyroxinemia and is considered a reliable non invasive marker of bone turnover. In this study an extra-increase of sBGP in hyperthyroid post-menopausal women towards pre-menopausal is reported, the persistence of high sBGP levels in patients affected by any type of hyperthyroidism after four months of therapy and a positive relationship with thyroid hormones (fT4). Therefore monitoring of this serum marker may be suggested also in patient chronically treated with 1-thyroxine to avoid, if possible, overzealous therapy. PMID- 1296149 TI - [The TRH test in Turner syndrome]. AB - In order to evaluate the functionality of the hypothalamic-hypophyseal-thyroid axis in Turner's syndrome (TS), 27 subjects, aged between 5.1 and 16.1 years old, were studied, 14 of whom were karyotype 45,XO and 13 affected by mosaicism. The TRH test (200 mcg i.v.) was performed in all subjects using a single bolus. TRH titers were assayed in serum samples collected at 0, 15, 30, 60 and 90 minutes, and anti-microsome and anti-thyroglobulin, T4 and T3, were assayed in the basal sample; the latter were also assayed in the blood sample collected at 120 minutes. These results were compared with those obtained using the same test in a group of age- and sex-matched controls. Anti-thyroid antibodies and basal levels of T3 and T4 were within the norm in 26 subjects; a high basal value of TSH was only found in one patient with chromosomic mosaicism with an elevated response to TRH and a high titer of anti-microsomic antibodies. Apart from this no statistically significant differences were found in patients compared to control subjects in relation to TSH values at all stages of the test and between the two groups of TS; no significant results were found in the comparison between the areas below the curves (AUC). On the basis of these results the Authors conclude that it is not possible to reveal alterations in thyroid function attributable to hypothalamic and hypophyseal anomalies in this group of patients either with karyotype 45,XO and mosaicism. PMID- 1296148 TI - [Randomized comparative study using carbocalcitonin i.m. vs carbocalcitonin nasal spray vs ipriflavone x os in the treatment of post-menopausal osteoporosis]. AB - A comparative study of 90 post-menopausal osteoporotic women, has been carried out. The patients were divided in 3 homogeneous groups. According to 3 different schemes: Group A = 30 patients received carbocalcitonin i.m. 40 UMRC/day/1 month and 40 UMRC/alternating days/2 months followed by 1 month of wash-out for 11 months; Group B = 30 patients received carbolcitonin nasal-spray 80 UMRC/day/1 month and 80 UMRC/alternating day/2 months followed by 1 month of wash-out for 11 months; Group C = 30 patients received ipriflavone x os (600 mg/day/3 months followed by 1 month of wash-out for 3 times). BMC significantly was increased in all Groups after 7 and 11 months. In conclusion, carbocalcitonin and ipriflavone seem to show a similar improving densitometric effect in post-menopausal osteoporosis. PMID- 1296150 TI - [Association of hyperthyroidism and diabetes mellitus. Description of a case with partial recovery of pancreatic beta-islet function]. AB - The coexistence of Graves' disease and insulin-dependent diabetes mellitus is well known among autoimmune polyglandular syndromes and sustained by common underlying immune pathogenic factors. Hyperthyroidism itself may lead to impaired glucose tolerance in subjects with intact beta-cell function through various not well clarified mechanisms and treatment of thyroid hyperfunction, on the other side, generally ameliorates the degree of metabolic control when diabetes is pre- and/or coexisting. We report a case of Graves' disease associated with diabetes mellitus, in which a partial recovery of insulin secretion is documented after euthyroidism was restored. PMID- 1296151 TI - [A new future for beta blockers: metoprolol reduces mortality and the need for heart transplantation in patients with dilated cardiomyopathy]. PMID- 1296152 TI - [The role of Doppler echocardiography in assessing left ventricular diastolic function. Case histories]. AB - The aim of this study was to provide a further contribution to evaluate the alterations induced by age on a number of simple Doppler indexes of left ventricular diastolic function. A population of 48 healthy subjects aged between 15 and 78 years old was examined using pulsed Doppler analysis of the left ventricular refilling flow. Linear regression analysis revealed a significant inverse correlation between age and peak speed during rapid refilling (r = 0.80); between age and the ratio between peak speed during rapid refilling and peak during atrial systole (r = -0.92); between age and deceleration time of peak E wave speed, although on the contrary the peak speed of diastolic refilling flow during the atrial systole (r = 0.81) increased significantly with age. Variance analysis showed that indexes of left ventricular diastolic function and age continued on the contrary to be significant n the population as a whole and in both sexes. From these findings it is clear that in the different age groups (15 29, 30-49, 50-65, and over 65) the peak speed of rapid refilling flow was significantly lower in over-65-year-olds than in elderly, middle-aged and young subjects (55 +/- 0.8, 60 +/- 0.5, 65 +/- 0.7 and 75 +/- 0.6 respectively; p < 0.001). The ratio between the peak speed of rapid refilling and that during the atrial systole was lower in over-65-year-olds compared to elderly subjects, middle-aged subjects or the youngest age group (0.94 +/- 0.09, 1.05 +/- 0.13, 1.96 +/- 0.21 and 2.68 +/- 0.50 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296153 TI - [Risk stratification in patients with a first myocardial infarct based on simple clinico-instrumental variables]. AB - It is an acknowledged fact that the prognosis for patients with a first myocardial infarction depends mainly on the degree of residual left ventricle function. We wanted to evaluate the importance that certain simple clinical and instrumental variables can have in stratifying post-infarction cardiovascular risk with particular emphasis on chronic obstructive lung disease (COLD). We selected 97 out of the 512 patients treated in the coronary intensive care unit (CICU) from February 1, 1988 to October 31, 1990 according to the following criteria: First myocardial infarction; no cardiogenic shock; no serious concomitant diseases with considered negative prognosis within 6 months. The following variables were considered for all the patients: age; sex; positive family history for ischemic heart disease; history of diabetes mellitus; arterial hypertension; previous cerebrovascular incident; history of obstructive arteriopathy of the lower limbs, of angor and COLD. The following tests were performed on all the patients: echocardiogram prior to discharge form the CICU; angiocardioscintigraphy with Tc-99 between the 20th and 30th day following the acute event; bicycle ergometer stress test on the 30th day. END POINTS: general mortality; cardiac mortality; non-fatal reinfarction; residual angina at 3 months. All the patients were treated with aspirin (325 mg/die) and/or heparin (12,500 units subcutaneously). All 97 patients were monitored for a mean follow up time of 19.8 months. General mortality was 2.08% (for reinfarction) 24 (24.7%) non-fatal cardiac events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296154 TI - [The use of ergonovine in the hemodynamics laboratory]. AB - In our department we have reviewed the use of ergonovine maleate as a provocative agent for inducing coronary spasm during coronary arteriography. From January 1978 to December 1991 the test has been performed in 116 patients. According to their symptoms, the patients were divided into 4 groups: (A) patients with exertional angina: 16 patients (13.8%), (B) patients with angina at rest: 64 patients (55.2%), (C) patients with atypical chest pain: 29 patients (25%), and (D) patients with previous myocardial infarct: 7 patients (6%). We have subdivided the patients with angina at rest, according to the electrocardiogram recorded during pain, into: (1) 16 patients with ST-segment elevation; (2) 14 patients with ST-segment depression or T wave inversion; (3) 5 patients with electrocardiogram unchanged during angina; (4) 29 patients with no electrocardiogram recorded during angina. In 67 patients (57.7%) the coronaries were normal, 17 patients (14.6%) had mild irregularities, 26 patients (22.4%) had non critical fixed obstructions (< or = 70%), and in 6 patients (3.5%) there were fixed coronary narrowings > or = 70%. The left ventricle was normal in 85 subjects (73.2%), hypo or akinetic in 31 (26.8%). After routine coronary angiography and ventriculography, ergonovine maleate, 0.05 up to 0.4 mg, was given intravenously. The ergonovine test was considered positive when a focal spasm narrowed a normal coronary artery, or one with a mild fixed obstruction (< or = 50%) to more than 70%, or when a 70% stenosis became occluded. The development of angina and/or electrocardiographic changes were not taken as a criteria of positivity. Thirteen tests (11.2%) were considered positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296155 TI - [Heart surgery complications during diagnostic coronary angiography. The experience of a nondepartmental hemodynamics laboratory]. AB - The records of the Catheter Laboratory at S. Carlo Hospital in Milan (a District General Hospital without Cardiac Surgery Unit) between 1989-1991 were reviewed to determine how often emergency coronary by-pass surgery was performed because of a complication arising during elective coronary arteriography. A total of 1,009 cardiac procedures were performed, 876 (87%) were confined to left ventricular angiography and coronary arteriography in patients with suspected coronary artery disease. Our Catheter Laboratory complications rate was low: death 0.1%, stroke 0, non fatal myocardial infarction 0.8%, arrhythmia 0.5%, femoral haematoma 0.7%, emergency cardiac surgery 0. Case selection, seniority of operators, femoral approach (98% of the cases) with coronary catheters 6 French can explain these good results. In our experience coronary angiography at a District General Hospital is safe, feasible and diagnostic. Besides our main problem is the non emergency access to a Cardiac Surgery Unit after coronary arteriography: our patients have to join a long waiting list at major Regional Centres with an increase in cardiac events. PMID- 1296156 TI - [The fibroblast, definition of its phenotype by its "programme" of biosynthesis of the extracellular matrix]. AB - This presentation is an introduction to a symposium focusing on the fibroblast, a virtually ubiquitous cell which is cultured in many laboratories. The traditional definition of the fibroblast based solely on morphological criteria, which has satisfied most biologists for years, now needs reappraisal. The papers delivered at this symposium addressed this issue. Investigations ranged from the phylogenetic origin of fibroblasts in sponges, studied by R. Garrone, to the phenotypic modulations leading to the "myofibroblast" reported by G. Gabbiani, whose manuscript was unfortunately received too late for the conference. The present article describes how the fibroblast can be defined on the basis of its programme for producing extracellular matrix macromolecules. This programme includes a qualitative aspect, i.e., the selection of genes to be expressed: collagen types, variations in alternative splicing patterns of matrix proteins- and a quantitative aspect, i.e., the precise spatial and temporal regulation of production of "selected" macromolecules in order to meet the body's needs. This programme can be studied experimentally, and data are accumulating on the mechanisms involved and on its regulation through intrinsic factors (acting on the genome) and extrinsic and epigenetic factors (vitamins, hormones, nutrition...). Several French laboratories have supplied useful contributions to this research. The results of their investigations, which cover part of this field, are reproduced in this issue of this revue. PMID- 1296157 TI - [Synthesis and supramolecular organization of components of the extracellular matrix by fibroblasts cultured in a collagen lattice]. AB - Fibroblasts cultured in a collagen gel contract and organize the gel into a three dimensional matrix of collagen fibers. Within this matrix, the fibroblast cell cycle is blocked at the G1 phase but also at the G2 phase. The fibroblasts produce the main extracellular matrix components (collagen, noncollagen proteins, glycosaminoglycans), although in small amounts. Studies using this in vitro model with radiolabeled precursor substances (14C proline, 3H glucosamine) demonstrated production of supermolecular complexes which resisted to proteolysis by pepsin and collagenase and could not be isolated by saline precipitation. Polyclonal antibodies identified type I collagen, type VI collagen and fibronectin in this coherent supermolecular structure. The presence of glycosaminoglycans was also demonstrated by alcian blue precipitation. PMID- 1296158 TI - [Modulation of the organization of the extracellular matrix and the production of collagen by interferon gamma in three-dimensional cultures of normal and sclerodermic fibroblasts]. AB - Recent studies have shown inhibition of collagen synthesis by interferon gamma (IFN-gamma) in monolayer human fibroblast cultures on a plastic solid phase. However, the existence of this effect in vivo has not yet been demonstrated. Three-dimensional fibroblast cultures in collagen matrices (collagen lattices or dermal equivalents) provide a more physiological model than conventional cultures and fairly closely simulate in vivo conditions. This model was used for studying effects of IFN-gamma on normal and scleroderma fibroblasts. IFN-gamma induced a dose-dependent inhibition of fibroblast-mediated retraction of collagen lattices. IFN-gamma also inhibited total protein and collagen synthesis. Scleroderma fibroblasts were especially susceptible to the inhibitory effects of IFN-gamma. Since fibrotic scleroderma lesions are associated with tissue retraction and increased production of extracellular matrix macromolecules, these data confirm the potential value of IFN-gamma for the treatment of scleroderma and other fibrotic diseases. PMID- 1296159 TI - [The keratocyte or fibroblast of the cornea: morphological and biochemical characteristics in normal stroma and a few cases of corneal dystrophies]. AB - Keratocytes are differentiated mesenchymal fibroblast which are specialized in the production and maintenance of the transparent corneal stroma. These elongated cells with large nuclei and scant cytoplasm produce the collages, proteoglycans, and glycoproteins which make up the stroma, as well as the enzymes involved in post-translation modifications and catabolism of these macromolecules. The characteristic morphological features and specific metabolic activity of keratocytes undergo significant changes during tissue repair and in several corneal diseases. Alterations in keratocyte biosynthetic activity, regardless of their cause, ultimately lead to fibrillar alterations responsible for a loss of corneal transparency. PMID- 1296160 TI - [Inhibition of elastase activity in human gingival extracts by elastin peptides]. AB - Effects of elastin peptides on elastase activity of gingival biopsy specimen extracts were studied in vitro and in vivo. All the extracts from biopsy specimens from 15 patients with a variety of periodontal diseases demonstrated fairly marked elastase activity. In vitro, addition of elastin peptides produced a mean inhibition of 54% +/- 14% with a concentration of 0.25 mg/ml and a mean inhibition of 90% +/- 6% with 2.5 mg/ml. In vivo treatment of gums with a paste containing 1% elastin peptides reduced elastase activity by 47% in 7 of 8 patients. These data suggest that elastin peptides are effective inhibitors of periodontal elastase activity and may be useful in preparations used for the preventive or curative treatment of periodontal diseases with tissue lysis. PMID- 1296161 TI - [Integrins]. AB - Cells and extracellular matrix components have complex interactions which are involved in many biological processes throughout the life span. These cell-matrix interactions are mediated by receptors, of which some are integral membrane proteins. The aim of this short article is to review the integrin family, the overall structure of integrins, their distribution and their role. These new data will undoubtedly contribute to improved understanding of the physiological and pathological processes involving connective tissues. PMID- 1296162 TI - Reproducibility of cutaneous electrogastrography in the fasting state in man. AB - Cutaneous electrogastrography (EGGc), the recording of gastric electrical activity from the cutaneous abdominal surface, still presents a series of difficulties connected with the interpretation of signals. In this study, the authors evaluated the reproducibility of electrogastrographic data over a period of time by making recordings on three consecutive days in a group of healthy subjects. The recordings (lasting 1 hour) were made in the morning on fasting subjects. Three sets of bipolar cutaneous electrodes were placed on the abdomen around the pyloric radiological projection and the couple 3-6 corresponded to the antral axis. The spectral analysis of data was computed by fast Fourier transform. Their data confirmed that the 3-6 couple, corresponding to the antral axis, provides the strongest EGG signal. Each subject's mean gastric frequency and power were evaluated on the three consecutive recording days. The mean frequency was 2.83 +/- 0.22, 2.89 +/- 0.23, and 2.86 +/- 0.16 cpm on day I, day II and day III respectively. The mean power was 54.80 +/- 21.34, 46.86 +/- 21.52 and 49.25 +/- 19.55 microV 2 on day I, day II and day III respectively. The analysis of variance showed that the mean gastric frequency and power were not significantly different on the three days (p > 0.05). This shows that the frequency of the EGGc signal remains stable in the course of time and hence that EGGc is a reliable method of studying disorders in gastric electrical rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296163 TI - [Soluble interleukin-2 receptor assay is unhelpful in chronic inflammatory rheumatism]. AB - The level of soluble interleukin-2 receptors (SIL2-R), which reflects lymphocyte activation, is often described as a useful parameter for evaluating disease activity and progression in patients with inflammatory conditions. Serum SIL2-R was assayed using a sandwich ELISA method in 98 subjects including 38 controls (C), 36 patients with ankylosing spondylarthropathy (AS) and 24 patients with rheumatoid arthritis (RA). SIL2-R levels were higher in RA patients than in controls and AS patients (p < 10(-4)), whereas the difference between AS patients and controls was small (p = 0.02). In RA patients, SIL2-R levels were not correlated with any of the clinical or biological parameters studied and remained unchanged during clinical improvements. In the AS group, SIL2-R levels showed no correlations with inflammation parameters (CRP, IgA) and was similar in patients with and without HLA B27 or appendicular joint involvement. This study failed to provide any evidence that SIL2-R levels are helpful for monitoring patients with inflammatory joint disease. PMID- 1296164 TI - [A programme of eradication of rabies by vaccination of the fox]. PMID- 1296165 TI - [L-carnitine: metabolism, functions and value in pathology]. AB - Although L-carnitine is not considered as an essential nutrient, endogenous synthesis may fail to ensure adequate L-carnitine levels in neonates, especially those born prematurely. Free L-carnitine is found in many foods, mainly those from animal sources. Absorption of free L-carnitine is virtually complete. Lysine and methionine are necessary ingredients for the biosynthesis of L-carnitine. All tissues in the body can produce deoxy-carnitine but, in humans, the enzyme that enables hydroxylation of deoxy-carnitine to carnitine is found only in the liver, brain and kidneys. Complex exchanges of carnitine and its precursors occur between tissues. Muscles take up carnitine from the bloodstream and contain most of the body carnitine stores. L-carnitine and L-carnitine esters are eliminated mainly through the kidneys, which may play a central role in the homeostasis of this compound. Thyroid hormones adrenocorticotrophin (ACTH), and diet all influence urinary excretion of L-carnitine. Free L-carnitine can be assayed in plasma and urine and is occasionally measured in muscle biopsy specimens. Plasma L-carnitine levels may not accurately reflect L-carnitine body stores. L carnitine ensures transfer of fatty acids to the mitochondria where they undergo oxidation. This process is associated with production of short-chain acylcarnitine which exit from the mitochondria or peroxisomes. L-carnitine ensures regeneration of coenzyme A and is thus involved in energy metabolism. L carnitine also ensures elimination of xenobiotic substances. Carnitine deficiencies are common. Currently, these deficiencies are classified into two groups. In deficiencies with myopathy, only the muscles are deficient in L carnitine, perhaps as a result of a primary anomaly of the L-carnitine transport system in muscles. In systemic deficiencies, L-carnitine levels are low in the plasma and in all body tissues. Systemic L-carnitine deficiencies are usually the result of a variety of disease states including deficient intake in premature infants or long-term parenteral nutrition; renal failure; organic acidemias; and Reye's syndrome. Modifications in L-carnitine metabolism have also been reported in patients with diabetes mellitus, malignancies, myocardial ischemia, and alcohol abuse. A large number of supplementation trials have been carried out. PMID- 1296166 TI - [Gastro-protection in vivo and in vitro]. AB - Experimental evidence coming from Andre Robert studies indicates that prostaglandins (PG) administered exogenously or released endogenously by mild irritants prevent the formation of gross mucosal lesions induced by various ulcerogens such as absolute ethanol, bile salts, hypertonic solution and acidified aspirin. This action appears to be independent of their gastric inhibitory effects. Mild irritants such as 5 mM NaCl, 20% ethanol and 20 mM taurocholate prevent gastric necrosis through adaptive cytoprotection involving an increase in the generation of endogenous PG. In addition, PG have been shown to increase gastric mucosal blood flow and to stimulate mucosal bicarbonate as well as mucus secretion and these effect may contribute to their gastro protective action. As demonstrated recently, PG prevented the damage of isolated gastric glands in vitro condition, where systemic, neural and hormonal factors are excluded. Gastro-protection is not the unique property of PG, however the mucosal generation of protective PG is essential for gastro-protective effects of solcoseryl. This paper reviews not only protective factors but also the mechanism and possible pathogenic implications of three related compounds thromboxanes, leukotrienes and platelet activating factor (PAF) in acute mucosal injury by topical irritants. The release of these mediators have been thought to be involved in the mechanism of mucosal injury, especially damage to the microvascular endothelium. Whether gastro-protection plays crucial role in the mechanism of ulcer healing remain unknown, however in chronic studies, PG failed to affect the speed of ulcer healing. On the other hand, epidermal growth factor (EGF) exhibits both gastro-protective and ulcer healing properties due to the potent trophic action and to the stimulation of polyamine biosynthesis. The accumulation of EGF in a large quantities in the ulcer area by the antiulcer drugs such as sucralfate and De-Nol may explain their well-known enhancing effects on ulcer healing. PMID- 1296167 TI - [Is standardization possible in immunohistochemical examination?]. AB - Immunohistochemistry has become an important tool in research and in surgical pathology. Rapid growth of a new methods in immunohistochemistry supplement traditional histochemical and histological light microscopy investigations. Immunohistochemistry has given pathologists a chance to location different antigens on the cell surface as well as in the cell compartments. The expression of antigens are mostly influenced by factors connected with tissue processing; fixation and embedding. The aim of present article is to show the role of these factors and their influence on some immunohistochemical staining results. Not all the problems are discussed here, the main goal which authors would like to obtain is to show the way how to solve problems which can occur during immunohistochemical staining procedure. They want also to delineate the importance of standardization in immunohistochemistry to make the results more reliable between different laboratories. PMID- 1296168 TI - Some ultrastructural aspects of Helicobacter pylori gastritis. AB - Ultrastructural examinations of biopsy specimens of the gastric mucosa were performed in 20 patients with chronic gastritis proven by endoscopy and microscopy. The presence of the Helicobacter pylori bacteria was found in close contact with epithelial cells of the antrum and corpus of the stomach. The bacteria were not present in the areas of frequently observed intestinal metaplasia. There were ultrastructural changes on the surface and within the cytoplasm of the epithelial mucous cells, which indicated their disturbed metabolism. PMID- 1296169 TI - Reactivity of bronchoalveolar space cells in lung asbestosis. AB - Preliminary studies to evaluate lymphocyte subsets bronchoalveolar lavage (BAL) and blood were carried out in a group of patients with lung asbestosis. The assessments were made by an indirect immunofluorescent method using monoclonal antibodies as a marker. The results were recorded on a flow cytofluorometer FASC can. As compared with a control group, the patients with lung asbestosis showed a slight decrease in the total level of T lymphocytes (CD3) in BAL, however with a clearly disturbed proportion between T-helper (CD4) and T-suppressor (CD8) lymphocytes, which led to a decreased CD4/CD8 ratio. The blood level of T lymphocytes and their subsets in these patients approximated that in the controls. Heavy smoking was also found to enhance disorders in their number and proportion. The assessment of B lymphocytes (by using polyclonal antihuman immunoglobulins (sIg/FITC) showed a significantly high level of these lymphocytes in BAL with simultaneously low levels in blood in the same patients with lung asbestosis. We did not find a clear synergic effect of cigarette smoking on the levels of B lymphocytes in the studied group. PMID- 1296170 TI - Comparison of porphyrin content in the cortex and medulla of the kidneys and adrenals of patients dying from chronic circulatory insufficiency. AB - Taking into account a correlation between the metabolism of porphyrins and hormones, and especially the metabolic interactions between the kidneys and adrenals, preliminary pilot studies were carried out on porphyrins in the kidneys and adrenals, separately in the cortex and in the medulla of these organs. The material was taken from 11 men and 8 women dying from circulatory insufficiency with vasculogenic renal fibrosis, and without changes in the adrenals. In all cases the concentration of porphyrins was much higher in the adrenals than that in the kidneys, while the content of uro-, copro-, and protoporphyrin was always higher in the adrenal medulla then that in the cortex. Discussing the results obtained the author suggest a correlation between disturbances of the reno adrenal feedback, and an extremely increased concentration of porphyrins in the adrenal medulla which could be caused mainly by connections between the metabolism of catecholamines and porphyrins. PMID- 1296171 TI - Endometrial stromal neoplasms of the uterus. A clinicopathologic study. AB - A clinicopathologic study of uterine endometrial stromal tumors (EST) has been performed with special emphasis on histologic and immunohistochemical differential criteria and prognostic factors. The material comprised three stromal nodules (SN), twelve low grade stromal sarcomas (LGESS) and five high grade stromal sarcomas (HGESS). Previously unreported endolymphatic growth was found within one SN. EST showed an association of mitotic index (IM) with atypia, degree of stromal differentiation, additional non-stromal differentiation and venous invasion. IM was the best criterion in the differential diagnosis of LGESS and HGESS and the most significant histologic prognosticator. The present study shows that a histologic grade of stromal sarcoma was a more significant prognostic factor than pTNM stage. The results suggested that clinicopathologic classification of EST could be supplemented by including the following subgroups: a) SN--without intravascular growth, and potentially malignant SN--with endolymphatic growth within the tumor; b) LGESS with IM < 2 and no atypia, and LGESS with 2 > IM < 10 and mild atypia; c) HGESS with 10 > IM < 20 and moderate atypia, and HGESS with IM > 20 and marked atypia. Contrary to common view these observations indicate that the distinction of some SN and LGESS from stromal hyperplasia is possible in an endometrial curretage material. PMID- 1296172 TI - Granular cell tumour (Abrikossoff tumour) of the bronchus. PMID- 1296173 TI - The clinicomorphological correlations in Schoenlein-Henoch nephropathy in children. AB - Clinicomorphological analysis has been performed in Schoenlein-Henoch nephropathy. Various clinical symptoms are accompanied by morphological changes of variable type and severity. Electron microscopy is a major tool for evaluating these changes. It relatively frequently modifies the diagnosis made by light microscopy. It mainly concerns class I and VI changes (according to a grading system of the International Study Group of Kidney Diseases in Childhood). It was shown that late prognosis was largely determined by the type and severity of morphological changes. Varying severity of changes in individual glomeruli in the same specimen requires in each case a comparison of results obtained by electron microscopy with those obtained by light microscopy in semithin sections. In three children biopsy was repeated. Progression of morphological changes was found in one child. He developed renal failure. In one child morphological changes on first biopsy did not differ from those on second biopsy. Repeated biopsy was performed due to the presence of hypertension. In one child with persistent proteinuria repeated biopsy showed marked attenuation of morphological changes. PMID- 1296174 TI - Thin basement membranes syndrome: a rare cause of erythrocyturia. AB - The results of the studies in five children with the syndrome of thin basement membranes have been discussed. A comparison of clinical data with the morphological ones shows that recognition of erythrocyturia or hematuria necessitates familial examinations and long-term follow-up. Final diagnosis of this syndrome may be made only by means of electron microscopy. PMID- 1296175 TI - Focal segmental glomerulosclerosis in children. AB - Clinical and morphological examinations in 25 children with the diagnosis of focal segmental glomerulosclerosis (FSG) show that: 1. electron microscopy permits a detection of FSG in its early stage when light microscopy does not reveal any changes, and immunomorphological studies do not show deposits 2. in this stage small focal interstitial changes may be visible 3. ultrastructural studies reveal changes in case of nonspecific light microscopy i.e. suggesting mesangial glomerulonephritis 4. in doubtful cases it is useful to repeat biopsy. PMID- 1296176 TI - Membrane-bound tumour necrosis factor alpha: immunocytochemical and ultrastructural studies of human monocytes and monocytic cell line and its induction by tumour cells in vitro. AB - Monoclonal antibody against recombinant human tumour necrosis factor alpha (rTNF) was used for the immunochemical detection of TNF in human blood monocytes and monocytic cell line U 937. Cells stimulated with phorbol myristate acetate (PMA) showed strong surface but not cytoplasmic staining. Unstimulated cells demonstrated weak or no staining. At early time after stimulation (1-2h) a spot reaction was seen in the Golgi area of the cytoplasm of stimulated cells. Coculture of tumour cells with monocytes also resulted in the induction of membrane TNF. Ultrastructural studies confirmed TNF localization within the cell membrane. These results indicate that TNF can be detected within the cells by immunocytochemistry which may make feasible studies on TNF appearance in cellular infiltrates in the tissues. PMID- 1296177 TI - Immunolocalization of epidermal growth factor (EGF) in human salivary glands detected with the new monoclonal antibody. AB - Epidermal growth factor (EGF) is biologically active peptide commonly seen in many human tissues and organs. Its high concentration has been found in the salivary glands. The purpose of the present study was to determine EGF immunolocalization in normal human major salivary glands using a new monoclonal antibody anti-EGF. The results were compared with EGF location determined by using two human antibodies (Oncogene, USA and ICI from dr Gregory, UK). Immunohistochemical studies were performed by the PAP method. All antibodies demonstrated EGF expression in the efferent pathways of the salivary glands, especially in their proximal segments. PMID- 1296178 TI - TFX-polfa in the treatment of transplantable Morris 5123 hepatoma in buffalo rats. AB - Buffalo rats with Morris 5123 hepatoma implanted into the muscles of a paw were treated with the preparation TFX produced by Polfa and/or amputation of the paw with the tumour. The results of treatment with TFX followed by amputation were significantly better than those of TFX treatment or amputation alone. PMID- 1296179 TI - Effect of vitamin E on the immunoreactivity of spleen cells in hyperlipidaemic rats. AB - Atherogenic (lipid-rich) diet suppressed mitogen-induced lymphocyte blastogenic responses in rats. Supplementation with vitamin E completely abolished the suppressive effect of the diet. The atherogenic diet also decreased the tumour necrosis factor alpha (TNF-alpha) activity produced by spleen macrophages, however, vitamin E supplementation failed to abolish this effect. Diet or supplementation had no measurable action on interleukin-1 (IL-1) production of macrophages. PMID- 1296180 TI - The incidence of hepatitis delta virus infection in chronic liver diseases in Hungary. AB - A study of hepatitis B and D virus markers in 118 hepatitis B virus seropositive patients suffering from histologically confirmed chronic liver disease is reported. The prevalence of hepatitis delta infection amounted to 13.6%, whereas active hepatitis delta virus replication was proven in 6 of the cases. On the basis of these findings, conclusions--similar to those published earlier--are drawn about the role of hepatitis delta virus in the progression of chronic liver diseases. It is suggested that HBsAg-IgM complex seropositivity in patients suffering from anti-delta positive chronic liver disease supports active hepatitis delta virus replication. PMID- 1296181 TI - The significance of detailed hepatitis B virus serology in chronic liver diseases. AB - Hepatitis B virus (HBV) markers were studied with Sorin RIA kits in serum samples from 390 patients suffering from histologically confirmed chronic liver disease. On the basis of negative HBsAg, anti-HBs, anti-HBc tests, HBV infection was excluded in 235 of the cases. The diagnosis was fatty liver and/or alcoholic hepatitis in 52%, while chronic active hepatitis and/or liver cirrhosis only in 21.7%. Part or present HBV infection was proven in 155. In 53% of these cases the diagnosis was chronic active hepatitis and/or liver cirrhosis, whereas fatty liver and alcoholic hepatitis occurred in 27.7%. Detailed HBV marker analysis was performed in 76 patients. Previous infection without replication (positive anti HBs and/or anti-HBc and/or anti-HBe) was proven in 48 cases, 12 patients had active HBV infection (positive HBsAg, HBe, IgM anti-HBc), while in 16 cases HBV integration (positive HBsAg, anti-HBc, anti-HBe) was proven. HBsAg-IgM complex seropositivity was shown in every case with active HBV replication. Because of therapeutic, prognostic and epidemiologic reasons, the significance of detailed HBV serology in chronic liver diseases is stressed. PMID- 1296182 TI - The distribution of ABO(H) isoantigens in urinary bladder tumours. AB - The distribution of blood group isoantigens (ABH) was studied with the specific red cell adherence test (SRCA); the red blood cells were visualized by the benzidine-peroxidase reaction. The H antigen was detected with Ulex europaeus agglutinin I lectin by direct immunoperoxidase technique. One hundred and seven bladder tumours were tested. It was found that blood group isoantigens diminished with immaturity (grade) and tumour invasiveness (T stadium). Patients with ABH blood group isoantigen deletion should be considered to be belong to a particularly high-risk group. The preservation of blood group antigens in grade II-III carcinomas may be useful in the choice of treatment (conservative or radical). In six cases in the area of squamous metaplasia of invasive carcinomas a strong false SRCA reaction was noticed detecting presumably the blood group determinants of the epidermal growth factor receptors. PMID- 1296183 TI - Clinical utility of quantitative assessment of liver haemodynamics in cirrhosis provided by dynamic hepatoscintigraphy. AB - Interrelationships between quantitative assessment of portal (%Qp) and arterial (%Qa) components of hepatic blood supply obtained by dynamic hepatoscintigraphy, and clinical variables characterizing the severity of liver cirrhosis and portal hypertension were studied in 25 cirrhotic patients. The variables, clinical state, size of oesophageal varices, ascites accumulation, sonographic stigmata of portal hypertension, liver mass and elimination rate of lidocaine and antipyrine were studied. The %Qa rose in proportion to the severity of liver injury estimated from the Child-Turcotte and McCormick grading scores. The mean %Qa for patients with Child A cirrhosis was significantly higher than that for 8 healthy subjects (34.8 +/- 7.9% vs 18.1 +/- 4.0; P < 0.01). The %Qp values showed relationship with the size of esophageal varices, provided discriminatory data with respect to the ascitic fluid accumulation and the development of intraabdominal collateral circulation. The liver mass had no impact on hepatic dual blood supply pattern, but was linked with the rate of antipyrine clearance. Neither antipyrine clearance nor lidocaine elimination rate corresponded to alterations of hepatic dual blood supply. The %Qp showed a negative correlation with the initial half-life of lidocaine, which was referred to lowered hepatic uptake of the drug. It is concluded that the quantitative assessment of %Qp and %Qa reflect the advancement of portal hypertension better than liver function failure does. PMID- 1296184 TI - Dipyridamole thallium-201 scintigraphy in patients with arteriosclerosis obliterans. Increased accuracy in identifying cardiac risk. AB - Forty-eight preselected patients (pts) with arteriosclerosis obliterans were investigated by dipyridamole thallium scintigraphy (DTS). No correlation was found between the distribution of positive or negative exercise ECG testing (ExECG) and isotopic risk-scores (P > 0.1 in the chi-square test). We assessed cardiac ischaemia in 12 pts with insufficient ExECG. Although only 2 pts had documented previous myocardial infarction, 20 pts exhibited irreversible perfusion defect. Silent reversible or irreversible ischaemia was identified in 12 pts (25%). Seven pts would not have been diagnosed to have coronary artery disease (CAD) even by ExECG. In conclusion, DTS was found very useful in these cases. We support a stepwise cardiac risk stratification before major vascular surgery. PMID- 1296185 TI - Macroethical responsibilities of societies of gynaecologists and obstetricians. AB - The theme of maternal mortality and morbidity is of transcending macroethical importance. High rates of maternal mortality and morbidity can be significantly reduced by cost-effective means that are not dependent on advanced biotechnology. It has been shown that a major cause of maternal mortality comes from women (i) bearing children too early or too late in their reproductive lives, (ii) too frequently or at insufficiently spaced intervals. If women were able to control their fertility in order not to have children at unwanted times in periods of their life when pregnancy is inimical to their health, the incidence of maternal mortality and morbidity would drop. Improved standards of women's education, both in general and in particular regarding women's reproductive health, would reinforce the understanding of how to protect and improve one's reproductive health, and would accelerate the decline of maternal mortality and chronic morbidities. Accordingly, the macroethical demands of respect for autonomy, beneficence and justice would coincide. The value of justice would be served not only regarding women themselves, particularly those who have traditionally been vulnerable by virtue of their growing age, or dependent status in their communities, but also regarding the children dependent on such women, and families also dependent on the services of such women, like mothers, wives, daughters and grand-daughters. PMID- 1296186 TI - The effect of sulphonylurea therapy on the outcome of coronary heart diseases in diabetic patients. AB - A retrospective study was performed on 1040 diabetic patients. The survival time of those treated with first generation sulphonylureas (n = 227) was considerably (P < 0.001) shorter after the first attack of angina pectoris (5 +/- 1 years, mean +/- S.E.) or acute myocardial infarction (6 +/- 1 years) than of those (9 +/ 1 years) on glibenclamide treatment (n = 144), with regime alone (n = 282) or treated with insulin (n = 387). The systolic blood pressure of patients with first generation sulphonylureas (166 +/- 1/91 +/- 1 mmHg) proved to be higher (P < 0.01) than those treated with glibenclamide (159 +/- 1/91 +/- 1 mmHg) or being on regime alone (155 +/- 1/89 +/- 1 mmHg) or on insulin (156 +/- 1/89 +/- 1 mmHg) treatments. Serum sodium level was found to be lower (P < 0.05) in patients treated with any kind of sulphonylureas (138 +/- 1 mmol/l) than in the other patients (143 +/- 1 mmol/l). During an observation period, 576 of patients died, 412 of them due to cardiovascular or renal failures. Among the diabetic subjects suffering from coronary heart disease no difference could be detected in risk factors except for higher systolic blood pressure. The shorter survival time of patients treated with first-generation sulphonylureas might be explained by the arrhythmogenic activity of first-generation sulphonylureas. Improvement in therapy, metabolic and cardiovascular alterations during the survey can not be responsible for the shorter survival time of patients treated with first generation-sulphonylureas. PMID- 1296187 TI - Experiences with functional insulin substitution: a follow-up study on control and patient compliance. AB - Functional insulin substitution, an insulin regimen made up of two daily injections of intermediate-acting insulin and prandial boluses of regular insulin, was to be introduced in 49 type 1 diabetic patients, as previous regimens consisting of two or three daily injections proved to be inefficient due to the patients lifestyle or inherent metabolic lability. Forty-five patients were treated with human insulin injected by NovoPen. In 38 cases therapy was changed in the frame of a one-week, small-group, inpatient, structured educational course. After a mean 14 months of follow-up metabolic status improved in 33 cases while there was further derangement in 16. Eighteen patients were practising true functional therapy, i.e. doing blood glucose tests before each injection. Further 22 diabetics were trying to achieve better metabolic control through 2-3 daily blood glucose tests and insulin dose corrections. The metabolic status was not affected by the frequency of blood glucose testing, rather by raising of the daily dose of short acting insulin in conjunction with the switch in therapy acting beneficially. All patients insisted on using NovoPen further on. PMID- 1296188 TI - LDL molecular size as risk factor in coronary artery disease. AB - Sera of 65 fasting human subjects--32 patients with coronary artery disease (CAD) aged 42-80 years and 33 healthy individuals--were tested for determination of nine lipid-related laboratory parameters, including protein-enriched LDL (low density lipoprotein cholesterol (LDL apo B) which is proportional to the amount of cholesterol per LDL particle. Three of the investigated parameters: protein enriched LDL, HDL cholesterol and apo B level differed significantly in the two groups (corrected P < 0.001, P < 0.009 and P < 0.009, respectively). Discriminant analysis revealed that protein-enriched LDL, LDL cholesterol, apo B and fasting triglyceride levels, but not HDL cholesterol, were the major discriminating factors for CAD in this study. Pearson correlation coefficients were calculated to describe the association between this size-related parameter and those which in both groups seem to be most strongly associated with it: apo B/A-I ratio (i), triglyceride (ii) and LDL/HDL ratio (iii). The analysis was done separately in the two groups. In the patients with CAD the influence of these three parameters were less decisive in the determination of the protein-enriched LDL than in the controls (corr. coeff.: (i) -0.155 vs -0.358; (ii) -0.624 vs -0.791; (iii) -0163 vs -0.471). In healthy volunteers the size-reducing effect of the same parameters was more profound, and at high values of LDL/HDL ratio, apo B/apo A-I ratio and triglyceride no distinction in LDL particle size can be made any longer between CAD patients and controls. Thus the improvement of the atherogenic profile does not seem to result in the reduction of risk for CAD in terms of LDL size and composition. PMID- 1296189 TI - Genotoxic effects of occupational exposure in the peripheral blood lymphocytes of pesticide preparing workers in Hungary. AB - Venous blood samples of 240 donors including 33 industrial and 60 historical controls were investigated in order to assess the genotoxic risk of pesticide preparing workers manufacturing monochlorinated benzene in Hungary. Mutation frequencies were determined in the hypoxanthine-(guanine)-phosphoribosyl transferase genes located on the X chromosome. DNA repair capacity was estimated following hydroxyurea treatment with subsequent UV irradiation of separated lymphocytes. Smoking as confounding factor of genotoxicity was also taken into consideration. Mutation frequencies were increased among the workers exposed to monochlorinated benzene in correlation with the duration of working time, compared to the controls. Mutation frequencies were lower than expected among non smoker, long-exposed workers. Smoking itself proved to be an effective confounding factor in the enhancement of point mutations in the case of long exposed workers. Smoking, however, caused no significant increase in the mutation frequency among the controls, and did not influence the DNA repair capacity of any of the groups. PMID- 1296190 TI - Relationship of serum antihistone antibody level to the patient's age. AB - The serum antihistone antibody (AHA) positivity of patients with various autoimmune diseases was compared with their positive reaction for antinuclear factor, rheumatoid factor, lupus erythematosus factor, cryoglobulin, immunocomplex, C-reactive protein, total protein, gamma globulin, IgG and IgM. In non-drug-induced SLE cases the predictive value of the AHA test was not higher than that of the other tests. It was striking that in 42% of patients with non autoimmune disease aged over 70 the AHA test was positive. Elevated IgM values were recorded in about 70% of positive AHA samples. PMID- 1296191 TI - A case of multiple myeloma with multilobulated and convoluted plasma cell nuclei. AB - We report a case of multiple myeloma with unusual cytological features. Cytological diagnosis was rendered difficult due to plasma cells with multilobulated and convoluted nuclei and this variant of myeloma seems to indicate poor prognosis. PMID- 1296192 TI - Burkitt's lymphoma in adults: a retrospective study of 46 cases. AB - The prognosis of Burkitt's lymphoma is generally considered to be poor, particularly in the advanced stages of the disease. Although recent chemotherapy protocols have given high rates of cure in children, there are few such reports concerning adults. We therefore conducted a retrospective analysis of the results for treatment of 46 adults in the Institut Gustave Roussy (IGR) between 1978 and 1987, in order to establish an effective treatment strategy for use in a prospective trial. The median age of the patients was 31 years and the majority were Caucasians of European origin. The clinical symptoms and course of the disease were similar to those in the pediatric situation and corresponded to the so-called non endemic forms observed in Europe and the United States. Presentation was generally extra-nodal, usually with abdominal manifestations. As a rule, the disease progressed rapidly and showed a high affinity for the central nervous system in the absence of specific prophylaxis, despite systemic therapy with highly active agents, particularly in the advanced stages. According to Murphy's classification, there were 6 stage I, 11 stage II, 19 stage III and 10 stage IV patients (3 of whom had CNS involvement). Treatment was heterogenous, although all the patients received polychemotherapy including anthracyclins. The best results were obtained from eleven patients treated according to the French Multicenter Protocols for pediatric Burkitt's lymphoma (LMB-84 and LMB-86). Kaplan-Meier 5-year relapse free survival rate among the 46 patients was 42% (stage I: 83%; stage II: 67%; stage III: 30%; stage IV: 30%). In order to standardize our therapeutic approach, we started a prospective study in 1988 using the unmodified pediatric protocol for our adult patients. PMID- 1296193 TI - Polycythaemia and portal vein thrombosis. AB - An attempt was made to discover the aetiology of acquired portal vein thrombosis in 12 polycythaemic patients who did not show any obvious local or regional cause. In addition to the diagnostic criteria of polycythaemia vera, erythropoietin was determined and cultures of erythroblast precursors were examined. The patients could be divided into 3 groups, in the first of which the definite diagnosis of polycythaemia vera was made on the basis of the PVSG (Polycythaemia Vera Study Group) criteria and bone marrow biopsy (5 patients). In the second group (5 patients), there was a diagnosis of possible polycythaemia vera based essentially on the finding of a spontaneous growth of medullary CFU-E. Finally, diagnostic criteria for polycythaemia vera were absent in two patients. On the basis of these findings, the physiopathology of the association of portal thrombosis and polycythaemia is discussed, in particular polycythaemia secondary to hepatic ischaemia. PMID- 1296194 TI - RRR-alpha-tocopheryl succinate modulation of human promyelocytic leukemia (HL-60) cell proliferation and differentiation. AB - HL-60 human promyelocytic leukemia cells can be induced to differentiate to granulocytes by retinoic acid and dimethyl sulfoxide or monocyte-macrophages by phorbol esters and 1,25-dihydroxyvitamin D3. These studies show that RRR-alpha tocopheryl succinate (TS) inhibits HL-60 cell proliferation and induces the HL-60 cells to differentiate toward a functionally deficient macrophage-like cell. TS at (15 micrograms/ml) was found to suppress HL-60 cell proliferation by 63% and 89% at 24 and 48 hours, respectively. This suppression of proliferation, however, is not permanent and requires the presence of TS. HL-60 cells treated for 48 hours with TS (15 micrograms/ml) were found to be blocked in the G2/M phase of the cell cycle. HL-60 cells blocked in the G2/M cell cycle phase by TS expressed normal levels of the transferrin receptor. TS-treated HL-60 cells exhibited binucleated morphological appearance; however, the cells did not exhibit chemotaxis, phagocytosis, or changes in the expression of the cell surface markers, CD11a and CD18. However, HL-60 cells treated for 48 hours with TS (15 micrograms/ml) could be stimulated to produce superoxide radicals and exhibited nonspecific esterase activity, two characteristics of macrophages. These results suggest a role for TS as an antitumor proliferative agent and as a modifier of human leukemia cell differentiation. PMID- 1296195 TI - Effect of dietary soybean and licorice on the male F344 rat: an integrated study of some parameters relevant to cancer chemoprevention. AB - The individual and combined effects of dietary toasted soybean meal (3.13-25%) and dietary licorice root extract (0.38-3.0%) on selected liver and intestinal enzyme levels and on clinical chemistry and histopathological parameters were evaluated on male F344 rats. All parameters were measured one and three months after the 50-day-old rats were started on the diets. By use of newly developed high-performance liquid chromatography-based analytic methods, measurable levels of daidzein (2.67 micrograms/ml) and glycyrrhetinic acid (7.87 micrograms/ml) were detected in the sera of rats on the 25% soybean and 3% licorice diets, respectively. Histopathological evaluations of organs and tissues yielded only nonsignificant strain-related changes. At all dosages, there were no significant soybean- or licorice-related anatomic lesions or hematologic changes. In the clinical biochemistry profile, soybean meal caused moderate but significant dose dependent decreases in serum cholesterol and increases in alkaline phosphatase, blood urea nitrogen, and phosphorus, which remained within the normal range. Liver glutathione transferase, catalase, and protein kinase C showed significant inductions (up to 50%) in response to increasing doses of soybean meal and licorice extract, with evidence for only marginal interaction between the two additives. Their effects on the intestinal mucosa were not significant. Ornithine decarboxylase levels, an indicator of promotional activity, were unchanged or repressed by the additives. The favorable effects of up to 25% toasted soybean meal and 3% licorice root extract on the levels of the four enzymes, without unfavorable changes in clinical parameters, might account in part for the chemopreventive activities of these additives. These effects would be in addition to direct inhibitory effects of known components in these additives on these or other enzymes or modulation of hormone activity that is not evaluated in this study. PMID- 1296196 TI - Attributable risk for diet, alcohol, and family history in the Melbourne Colorectal Cancer Study. AB - From the data obtained in a large comprehensive population-based case-control study of colorectal cancer (The Melbourne Colorectal Cancer Study), attributable risk was calculated for a family history of colorectal cancer in near relatives for diet (when > or = 5 of the 11 previously determined dietary risk factors were present) and for beer consumption (for rectal cancer only). The attributable risk was 11% in the presence of a family history of colorectal cancer and 46% in the presence of five or more dietary risk factors. The attributable risk for rectal cancer in the presence of beer consumption was 31% in males and 11% in females. These data are relevant in the consideration of primary prevention of colorectal cancer in Australia, but their general application needs to be approached with caution in view of major differences in the genetic background and the dietary practices in various regions of the world and in view of the uncertainty of what is achievable change, especially for dietary practices. PMID- 1296197 TI - Diet, alcohol, smoking, serum beta-carotene, and vitamin A in male nonmelanocytic skin cancer patients and controls. AB - A case-control study was conducted in Melbourne, Australia of 88 consecutive males admitted for the surgical removal of a nonmelanocytic skin cancer (histologically confirmed basal cell carcinoma and squamous cell carcinoma) and of 88 male control patients admitted for small elective surgical procedures. In both cases and controls, previous diet, alcohol consumption, and smoking habit were investigated and serum beta-carotene and vitamin A levels were measured. A statistically significant inverse relationship was found between the risk of skin cancer and a high intake of fish (p = 0.05); vegetables in general (p < 0.001); beans, lentils, or peas (p < 0.001), carrots, silverbeet (Swiss chard), or pumpkin (p < 0.001); cruciferous vegetables (cabbage, brussel sprouts, or broccoli) (p < 0.001); and beta-carotene- and vitamin C-containing foods (p = 0.004). Cases had a lower mean serum level of beta-carotene (p < 0.001) and vitamin A (p = 0.02) than controls. The incidence of skin cancer in the study was inversely related to the level of serum beta-carotene (p < 0.0001). The correlation coefficient between dietary beta-carotene/vitamin C and serum beta carotene was 0.22 (p = 0.04). Smoking and alcohol consumption showed no statistically significant association with the risk of nonmelanocytic skin cancer. The results were similar for both cell types. A high intake of vegetables including cruciferous vegetables, beta-carotene- and vitamin C-containing foods, and fish appears to be protective for nonmelanocytic skin cancer, and this deserves further study, as does the possible etiologic relevance of the low serum levels of beta-carotene and vitamin A. PMID- 1296198 TI - Ethanol calories do not enhance breast cancer in isocalorically fed C3H/Ou mice. AB - Mammary tumorigenesis is augmented when C3H/Ou mice are fed diet ad libitum but delayed when calories are restricted by 40%. Three feeding experiments were done to evaluate the effect of ethanol on mammary tumorigenesis in isocalorically fed C3H/Ou mice: 1) ad libitum feeding of semipurified solid diet, with one group receiving 12% ethanol (15 g/kg/day) in the drinking water while controls received water alone; 2) isocaloric pair feeding of semipurified solid diet, with ethanol (4 g/kg/day) administered by gavage five time per week; and 3) isocaloric pair feeding of Lieber-DeCarli liquid diet, with one group receiving 29% of calories as ethanol (20 g/kg/day) in the diet. Despite administration of ethanol to isocalorically fed C3H/Ou mice for 65 weeks by three different methods, mammary tumor development was not enhanced. In two of the three ethanol-consuming groups, weight gain and mean body weight were less in the ethanol-consuming mice than in the controls, despite equal total calorie consumption. In only one ethanol consuming group, where mice received ethanol as a 12% solution in the drinking water, was any difference noted in the tendency to develop mammary tumors. In this case, delay in tumorigenesis was apparent in the ethanol-consuming animals (p = 0.03). These findings do not support the hypothesis that ethanol calories augment the risk of breast tumorigenesis among breast cancer-prone mice consuming isocaloric diets. Instead, reductions in weight gain and body weight among ethanol-consuming mice and an apparent reduction in mammary tumorigenesis in one of three experimental groups suggest that ethanol may decrease metabolic utilization of calories and hence contribute to lowered energy availability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296199 TI - Diet in the epidemiology of bladder cancer in western New York. AB - We present the dietary epidemiology of bladder cancer while controlling for a number of lifestyle and environmental risk factors in a study of 351 white male cases with histologically confirmed transitional cell carcinoma of the bladder and 855 white male controls selected from Erie, Niagara, and Monroe counties of western New York from 1979 to 1985. Usual diet was estimated by comprehensive interviews with use of a detailed food frequency questionnaire. An increased risk of bladder cancer was associated with higher kilocalorie intake, but only among those under 65 years of age, with the strongest pattern associated with fat intake. Further analyses of fat, carbohydrates, and protein, with adjustment for total kilocalories, resulted in a positive association of risk with fat intake and a decreasing risk with higher protein intake. Of the vitamins, carotenoid consumption appeared to decrease risk with increased consumption for those under 65 years of age. No significant differences between cases and controls were seen for intake of calcium, retinol, thiamin, riboflavin, niacin, vitamin C, vitamin D, and vitamin E. After adjustment for kilocalories and other confounders, higher intake of dietary sodium was associated with increased risk among both age groups, and the trends were statistically significant. The importance of diet in the etiology of bladder cancer is suggested by our findings. PMID- 1296200 TI - Dietary patterns and colon cancer in western New York. AB - Seven dietary patterns were identified among control subjects in the Western New York Diet Study (1975-1986) by application of principal components analysis to data from a 95-item food frequency interview. The results of case-control analyses of colon cancer risk for these patterns are presented. Cases were matched with neighborhood controls on the bases of age and sex; 205 colon case control male and 223 female pairs were obtained. The dietary patterns and intakes of energy, total fat, and dietary fiber were examined with logistic regression for their individual contributions to risk. In males, three of these dietary patterns were associated positively with fat and energy consumption; they elevated risk for colon cancer and accounted for more risk than did the specific nutrients. Control for energy and fat intakes allowed the protective influences of additional dietary patterns to be expressed. No patterns elevated risk in women; two patterns were protective for colon cancer. Controlling for energy and fat intake enhanced the protection afforded by one of these patterns but had no influence on that of the other. Measures of foods rather than single nutrients may be more inclusive of dietary exposures to risk as well as being related more directly to underlying health behaviors. Therefore they may be better able to account for risk in diseases with multiple causation. PMID- 1296201 TI - Diet and prostatic cancer: a case-control study in northern Italy. AB - The relationship between intake of various indicator foods and beverages and risk of prostatic cancer was assessed in 271 cases of prostatic cancer and 685 hospital controls recruited in two areas of northern Italy, the province of Pordenone and the greater Milan area. Increased risks were found for more frequent intake of meat [odds ratio (OR) in the highest vs. lowest consumption tertile = 1.4, 95% confidence interval (CI) 1.0-2.0], milk (OR = 1.6, 95% CI 1.1 2.4), fresh fruit (OR = 1.4, 95% CI 1.0-2.1), and vegetables (OR = 1.4, 95% CI 0.9-2.2). After allowance for the reciprocal confounding effect of various dietary habits, only frequent intake of milk seemed to be a significant independent indicator of prostatic cancer risk. There was also a clue that the unfavorable influence of frequent intake of a few food items (i.e. meat, fish, liver, ham and salami, milk and butter, and retinol) may be greater or restricted to older individuals (i.e., > or = 70 yrs of age). In conclusion, the present study confirms the presence of a moderate adverse effect of high intake of foods of animal origin, chiefly milk, while it suggests that a diet rich in fresh fruit and vegetables does not convey a protection. PMID- 1296202 TI - Lack of effects of selenium on N-nitrosomethylbenzylamine-induced tumorigenesis, DNA methylation, and oncogene expression in rats and mice. AB - The effects of dietary selenium deficiency and excess on N nitrosomethylbenzylamine-(NMBA) induced esophageal neoplasia in rats and forestomach tumors in mice and the effects of dietary selenium on DNA adduct formation and on the activities of DNA adduct-repairing enzyme and oncogene expression in rat esophagus were investigated. The esophageal and forestomach tumors were induced by administration of NMBA by gavage with a total dose of 39 mg/kg body wt in rats and 12 mg/kg body wt in mice. Neither selenium dietary deficiency (Se < 0.02 ppm) nor selenium excess (2.0 ppm) showed any significant effect on the incidence of tumors or number of tumors per tumor-bearing animal. For the DNA adduct formation studies, rats were given a dose of NMBA intraperitoneally after six weeks on the different selenium-containing diets. No significant difference in the amount of the DNA adduct O6-methyldeoxyguanosine was found among the different selenium-treated groups. In a parallel group of rats that did not receive NMBA, the levels of esophageal O6-methyldeoxyguanosine DNA methyltransferase were not significantly altered by dietary selenium levels. The c-myc oncogene expression in rat esophagus was induced by the administration of NMBA (3 mg/kg body wt) by gavage once a week for eight weeks. Dietary selenium did not show any effects on its expression. On the basis of the results of these studies, dietary selenium has no effects in the NMBA-induced tumor model. PMID- 1296203 TI - Lectin histochemistry of the human amnio-chorionic membrane complex. AB - The presence and distribution of glycoconjugates within the human amnion, chorion, and decidual tissues was examined histochemically following incubation with HRP-labelled lectins. Glycoconjugates within the cytoplasm of cells as well as the extracellular matrix of the maternal decidual layer and fetal chorio amniotic membranes reacted selectively with OFA, LTA, WGA, PSA, UEA-I, GSAI-B4, RCA-I, LFA, VVA, PHA-E, and GSA-II. Conjugated lectins specific for L-fucose stained components of amnion, chorion laeve, and decidua while other lectins bound glycoconjugates within decidua and at the junction between maternal decidua and fetal chorionic tissue. These observations suggest that the amnio-chorionic membrane complex may include several histochemically distinct and specialized subpopulations of glycoconjugates distributed within cells and the extracellular matrix. Although specific functions for these glycoconjugates have not been elucidated, they may mediate transport of amniotic fluid and/or facilitate maternal recognition of the developing fetus. PMID- 1296204 TI - Effect of calcium on mitochondria from human term placenta. AB - We describe here the effects of free Ca2+ on several functions of mitochondria from human term placenta. In the presence of 0.1 microM free Ca2+, an inhibitory effect on both ADP-induced respiration and succinate-DCPIP reductase activity was observed. At the same Ca2+ concentration, ATPase activity as well as various segments of the respiratory chain were stimulated. However, a higher free Ca2+ concentration (0.3 microM) was needed to stimulate progesterone synthesis. Our results suggest that Ca2+ plays an important role in the metabolic functions of mitochondria from human term placenta. PMID- 1296205 TI - Peroxidase: a novel pathway for chemical oxidation in human term placenta. AB - Hydrogen peroxide-dependent oxidation of xenobiotics in a crude fraction of human term placental membranes (nuclei, mitochondria and microsomes) was investigated. Guaiacol was employed as a model substrate. The rate of its oxidation was found to be dependent on the concentration of protein, H2O2 and the substrate as well as the pH of the buffer. Several other classical substrates for peroxidases from different sources viz. pyrogallol, benzidine, p-PDA, DMBD, ABTS, TMPD and TMBD and endogenous chemicals such as bilirubin and epinephrine were also found to undergo oxidation. The xenobiotic oxidizing capacity of the membranes was retained by CaCl2 (0.5 M) extract as well as by the partially purified enzyme obtained by affinity (Con A) chromatography. The H2O2-dependent chemical oxidation by the partially purified peroxidase was inhibited by NaN3 and KCN (IC50 values 41 and 23 microM respectively). These results suggest that peroxidase may be a major enzyme in human term placenta capable of oxidation of endogenous chemicals and xenobiotics. PMID- 1296206 TI - Evidence for inhibition by endothelium-derived relaxing factor of thromboxane A2 receptor-mediated vasoconstriction in the fetal vessels of the human perfused placenta. AB - Three inhibitors of the release or effects of endothelium-derived relaxing factor (EDRF), N-nitro-L-arginine, methylene blue and oxyhemoglobin, caused further increases in perfusion pressure during vascular constriction with submaximal concentrations of the thromboxane A2-mimetic, U46619 in fetal vessels of human placental lobules perfused in vitro. The results suggest the EDRF, released during constriction of fetal placental vessels in response to thromboxane A2 receptor stimulation, attenuates the vasoconstrictor response. Hence, impairment of EDRF release or function could contribute to the reduced placental blood flow observed in various disease states associated with increased thromboxane A2 production such as pre-eclampsia. PMID- 1296207 TI - Classics revisited: researches on pre-natal life by Sir Joseph Barcroft. PMID- 1296208 TI - Immunotitration of the catalase in the blood of Japanese subjects and mice suffering from acatalasemia and hypocatalasemia. AB - Catalase in hemolysates of normal, heterozygous hypocatalasemic and acatalasemic Japanese was immunotitrated with an anti-human blood catalase rabbit serum. Equivalence points were calculated from the regression lines between catalase activity added and catalase activity remaining in the supernatant. Catalase activities at the equivalence points of Japanese normal, hypocatalasemia and acatalasemia were similar. The results indicate that the specific activities of catalase in the normal and of the variant bloods are identical. Catalase in hemolysates of normal and variant mice was immunotitrated with an anti-mouse liver catalase rabbit serum. In contrast to Japanese acatalasemic subject, the equivalence points of catalase in heterozygous hypocatalasemic, homozygous hypocatalasemic, acatalasemic and normal hemolysates were different, and the ratios of specific activity in these variant mice to that in normal were 0.72, 0.46 and 0.21, respectively. The differences in catalase activities at equivalence points were also supported by the statistical analysis on parameters of regression lines of catalase activities remaining in the supernatant on catalase activities added in the immunotitration. These findings suggest that the molecular properties of residual catalase of Japanese acatalasemia and those of mouse acatalasemia are entirely different. PMID- 1296210 TI - Motional characteristics of K+ and Na+ in intact and sucrose-permeabilized rat lymphocytes. AB - Most, if not all, cells maintain an unequal distribution of Na+ and K+ against their environment. These two monovalent ions are in constant exchange between the cell and the extracellular space since both ions have proved to be permeable through the cell membrane. The distribution of Na+ and K+ in intact and "sucrose permeabilized" rat lymphocytes were studied ("sucrose-permeabilization" means homogenization in isotonic sucrose solution). Both the intact and the permeabilized lymphocytes were incubated in Hanks' solution and then transferred into K+, Na(+)-free isotonic sucrose solution. Alternatively, the cells were incubated only in the sucrose solution or in Hanks' solution. The Na+ and K+ content of the cells were determined at the conclusion of each period of incubation in the same or different medium. We found that K+ did not equilibrate under any conditions in intact lymphocytes but Na+ responded to changes of the incubation media. In the permeabilized cells Na+ freely equilibrated with the extracellular medium while K+ did not, although its concentration decreased compared to that of intact cells. PMID- 1296209 TI - Effect of thyroid hormones and their analogues on the mitochondrial calcium transport activity. AB - In this paper the authors studied the effects of thyroid hormones and their structural analogues on the mitochondrial calcium transport activities. The thyroid hormones, 3,5,3' L-triiodothyronine (LT3) and 3,5,3'5' L tetraiodothyronine (LT4) at physiological intracellular concentrations between 7.2 and 9 nM, decouple total Ca++ transport, as well as inhibit the passive transport of Ca++, either due to oxidation of pyruvate, malate or succinate or after inhibition with rotenone. The optical isomers 3,5,3' D-triiodothyronine (DT3) and 3,5,3',5' D-tetraiodothyronine (DT4) are less effective at all the used concentrations. Furthermore the structural analogues 3,3',5' L-triiodothyronine (LrT3), 3,5-dicloro, 3',5' L-diiodothyronine (LDiClT2) and 3,5 L-diiodothyronine (LT2) furnished even less effects on the same activities. The effect of the thyroid hormones and of their structural analogues has revealed that the mitochondrial calcium transport may be influenced both by a stereospecific interaction between hormones and protein ligands and by a lipophilic chaotropic action on the mitochondrial membranes lipids. In this context it is interesting to consider that both thyroid hormones and Ca++ transport activity are interacting with the energetic metabolism by means of phosphorylation and substrate oxidation mechanism. PMID- 1296211 TI - Non-Newtonian rheology of leukemic blood and plasma: are n and k parameters of power law model diagnostic? AB - When discussing the rheological properties of normal and leukemic blood it must be considered that blood is a suspension of cells in aqueous solution which is also known as plasma. Whole blood viscosity and plasma viscosity were determined by Rheometer LS30 which allows measuring whole blood and plasma viscosity in the middle and low shear rate ranges. The measurements of the viscosity showed that whole blood and plasma behave as non-Newtonian power law fluid. The values of n (non-Newtonian index) and k (consistency index) of power law fluid were calculated for both leukemic blood and plasma samples. The importance of this phenomenon for the micro-circulation is discussed. PMID- 1296212 TI - Transamination of some sulphur- or selenium-containing amino acids by bovine liver glutamine transaminase. AB - S-(3-aminopropyl)cysteine and Se-(3-aminopropyl)selenocysteine are deaminated by bovine liver glutamine transaminase. The corresponding alpha-keto acids, S-(3 aminopropyl)-thiopyruvic acid and Se-(3-aminopropyl)selenopyruvic acid, are produced which spontaneously cyclize to ketimine derivatives. They have been identified by comparing their UV absorption spectra and some chemical or chromatographic properties with chemically synthesized authentic samples. Also S (2-aminoethyl)homocysteine is the substrate for the enzyme. Kinetic parameters determined in comparison to thialysine and selenalysine show that neither the presence of a sulphur or a selenium atom nor the relative position of the atom in the carbon chain appreciably affects the substrate specificity of the enzyme. However, the length of the carbon chain has some influence on it. PMID- 1296213 TI - A study of the suitability of two methods used for describing the occlusal plane. AB - In this study an effort was made to determine which of the two commonly used methods of occlusal plane determination more precisely depicts changes induced by treatment or growth. Longitudinal lateral cephalometric radiographs of 70 individuals, 40 orthodontically treated and 30 with clinically acceptable occlusion, were used. Following an analysis of outcomes obtained through the conventional application of the Downs occlusal plane method and the functional occlusal plane method, there are indications that: 1) the Downs method may provide a better description of what happens to the occlusion following treatment; 2) the notion that the plane reconstructed using the functional method actually represents the location at which the occlusal function takes place is unsubstantiated; and 3) since it is possible that the results of this study could be influenced by the types of malocclusion, skeletal patterns, and methods of orthodontic treatment, further analyses are called for in order to make more conclusive determinations about these methods. PMID- 1296214 TI - Measurement and interpretation of changes in memory in response to drug treatments. AB - Drug-induced changes in cognitive functions such as memory are generally domain specific rather than general effects, that is, only some components of memory are altered. Changes in memory can be secondary to alterations in other cognitive domains such as attention, or non-cognitive domains (mood and arousal), or the direct result of alterations on those neurobiological systems that determine memory functions. The selective memory impairing effects of benzodiazepines are used to illustrate how cognitive neuroscience methods and theory can be useful in assessing the memory changes produced by psychoactive drugs. PMID- 1296215 TI - Toward a neuropsychology of memory in schizophrenia. AB - Three brain regions that have been the focus of recent interest in the neuropathology of schizophrenia include the frontal lobes, the basal ganglia, and the temporal lobes. We tested patients with chronic schizophrenia on three memory tasks, the successful performance of which depends on the integrity of each of these three brain regions. Comparisons between chronic schizophrenic patients and normal control subjects yielded the following results: (a) patients were impaired in remembering the temporal order of previously presented events; (b) patients were impaired on a motor task of procedural learning; and (c) patients showed normal priming effects in an implicit memory task despite their recall deficit in an explicit memory task. The significance of these findings lies in their relation to neuropsychological findings in patients with dysfunction in frontal cortical, basal ganglia, and medial temporal lobe structures. PMID- 1296216 TI - Remediation of neuropsychological deficits in psychiatric populations: rationale and methodological considerations. AB - The authors provide a literature review and methodological description of the emerging field of neuropsychiatric rehabilitation. Part I reviews literature that reveals compelling reasons for considering neuropsychological (NP) rehabilitation methods in patients with mental illness. NP deficits are prevalent in these patients and in contrast to psychopathology are predictive of social and occupational dysfunction, the most costly aspect of mental illness in both human and financial terms. NP deficits may explain the relatively poor outcomes from traditional vocational rehabilitation programs and there is evidence that they may be remediable. Part II summarizes methodological considerations required for research in this field. Methods for selecting optimal neuropsychiatric rehabilitation intervention techniques are reviewed and some suggestions are offered along with a brief theoretical discussion concerning their potential neural basis. Finally, design issues are reviewed, some tools for the measurement of outcome are offered, and methods are suggested for controlling for medications and environmental factors. PMID- 1296217 TI - Mental status testing in elderly Hispanic populations: special concerns. AB - The rapid growth of the older Hispanic population highlights the importance of accurately assessing the mental status of these individuals. Although several community surveys have reported relatively higher rates of cognitive impairment among older Hispanics, closer analysis has revealed excessive false positives and the underestimation of cognitive functioning. Problems inherent in the mental status testing of this group include the lack of appropriately translated and culturally sensitive instrumentation, the diversity of the population, differences in their educational experiences, and bias in the test-taking situation. Commonly used neuropsychological test batteries have generally been neither translated nor normed for Hispanic subjects. To minimize cultural differences, cross-cultural tests have used nonverbal content; however, nonverbal testing does not, in itself, remove cultural bias. Alternative methods of testing that may reduce bias include performance-based assessment of everyday living skills and measurement of basic psychophysiological responses. PMID- 1296218 TI - Cognitive deficits in delirium: assessment over time. AB - Delirium is commonly defined as a transient organic brain syndrome characterized by concurrent disorders of attention, perception, thinking, memory, psychomotor behavior, and the sleep-wake cycle. One of the difficulties in studying delirium is that symptoms tend to fluctuate over the course of the day. Pre-existing organic brain disease appears to be a significant risk factor for the development of delirium, and numerous studies have shown a high rate of delirium in patients with cerebrovascular disease, Parkinson's disease, and Alzheimer's disease. The cognitive deficits associated with delirium have not been widely studied in a systematic, quantitative fashion. Following resolution of the frank delirium, documented cognitive deficits can be observed, and may persist in a diluted form for a period of months. Residual cognitive deficits may be due to a minimal and persistent confusion or to an underlying brain disorder. PMID- 1296219 TI - Pharmacological treatment of the cognitive side effects of ECT: a review. AB - Electroconvulsive therapy (ECT) is an extremely effective treatment for a variety of psychiatric syndromes. However, it is frequently associated with transient cognitive side effects. Recent research has shown that these effects are sensitive to a number of treatment parameters, such as electrode placement and stimulus dosage, that the clinician may manipulate. However there have been relatively few efforts to determine if these cognitive side effects may be reduced or prevented by psychopharmacological intervention. In animals electroconvulsive shock (ECS) has been used frequently to screen for compounds which may improve cognition and memory. This paper reviews basic research studies on such compounds, as well as clinical trials in the treatment of various cognitive disorders. Studies using such compounds to reduce the cognitive side effects of ECT are exhaustively reviewed. The compounds that have been examined include: opioids, vasopressin, adrenocorticotropic hormone, other neuropeptides, cholinergic agents, nootropic agents, ergoloid mesylates, calcium-channel blockers, dexamethasone, thyroid hormone, and stimulants. PMID- 1296220 TI - Reliability and clinical concepts underlying global judgments in dementia: implications for clinical research. AB - The Clinical Global Impression Scale (CGI) is a recognized rating scale for global clinical judgments comprising scores for disease severity, change of disease conditions, and a so-called "efficacy index." In this report, the authors subject the CGI to a methodological analysis. Thirty-seven physicians working in psychogeriatric wards were interviewed on 12 patients each with a DSM-III diagnosis of a dementia syndrome. After the physicians made global judgments on the patients with the CGI, "personal" assessment criteria were elicited. The CGI data were correlated in the statistical analysis with the physicians' assessments of the patients on their personal criteria and on "recognized" assessment criteria obtained from DSM-III-R diagnostic criteria for dementia syndrome. Interrater reliabilities between physicians and nursing staff as well as retest reliabilities for the CGI criteria were also measured. While the CGI-severity reflects primarily the cognitive aspects of dementia, the CGI global assessment of change of the disease condition was poorly correlated with the assessments based on "personal" or the recognized DSM-III-R criteria. This was also indicated by the result that the reliability scores for CGI-severity were high and did not vary greatly, whereas the reliability scores for CGI change showed wide confidence intervals. PMID- 1296221 TI - Self-injurious behavior in the developmentally disabled: assessment techniques. AB - Self-injurious behavior (SIB) is a major cause of difficulty for the developmentally disabled person. Causes are varied, but medical, neurological, and psychiatric disorders should be considered before nonspecific approaches to treatment are chosen. A careful assessment should include a thorough medical and psychiatric evaluation as well as laboratory and diagnostic studies. Various assessment instruments are available to aid in the evaluation process and, to some extent, in the evaluation of the effectiveness of treatment for SIB. PMID- 1296222 TI - Self-injurious behavior in the developmentally disabled: pharmacologic treatment. AB - The current status of pharmacological treatments of self-injurious behavior (SIB) and aggression in persons with mental retardation and autism was reviewed in the literature. Much of the existing literature is derived from anecdotal clinical experience, with a relative lack of well-controlled studies to determine the efficacy of different treatments. Although all psychotropics have been used to manage SIB and aggression, particularly promising are the data on the use of opioid antagonists like naltrexone. Beta-blockers may also have some role, but more controlled, systematic studies are needed. Use of neuroleptics is on the decline because of their adverse effects, such as tardive dyskinesia and possible impairment of cognitive functions. We assert that the behavioral problems of SIB and aggression are at times manifestations of different psychiatric syndromes. They present in a modified, atypical form in the developmentally disabled population because of cognitive limitations. Further understanding and classification of the psychopathology associated with this behavior is essential for its successful treatment. PMID- 1296223 TI - Rating the severity of trichotillomania: methods and problems. AB - The capacity to measure the severity of trichotillomania is necessary for studies of the efficacy of treatment interventions. To date, researchers have used diverse methods, including: the adaptation of instruments designed for other purposes, counting episodes of hair pulling, counting hairs that have been pulled out, and both physician- and self-administered scales of severity or improvement. In this paper, the authors review the methods that have been employed, discuss problems in the measurement of trichotillomania, explore the potential for objective measures of hair loss and introduce a new instrument, the Psychiatric Institute Trichotillomania Scale. PMID- 1296224 TI - The Psychiatric Institute Trichotillomania Scale (PITS). PMID- 1296225 TI - The role of adenylate cyclase in neuropsychiatric disease. AB - Over the past decade the study of neuropsychiatric diseases has focused on investigating the integrity of various neurotransmitter and second messenger systems. The most extensively studied second messenger system in both human and rodent tissues has been the adenylate cyclase complex. The search for alterations of adenylate cyclase activity in diseased human tissues ranging from postmortem human brain to isolated lymphocytes has been both fruitful and controversial. Discrepancies are apparent between studies investigating alterations in this system in the human brain and peripheral tissues. Animal studies have proved invaluable for the elucidation of the role of the various components of the adenylate cyclase complex (such as the G proteins) in central neurones. Such studies have also contributed to the elucidation of the effects of psychotropic agents on this system. Clearly, alterations in the functioning of the adenylate cyclase complex have been identified in most neuropsychiatric disorders. The significance of such findings in the study of neuropsychiatric disease will be discussed and also the validity of the various tissue systems used in these studies. PMID- 1296226 TI - Methods of gene transfer into hepatocytes: progress toward gene therapy. PMID- 1296227 TI - Inherited disorders of mitochondrial fatty acid oxidation. PMID- 1296228 TI - Cholesterol gallstone formation. 1. Physical-chemistry of bile and biliary lipid secretion. PMID- 1296229 TI - Cholesterol gallstone formation. 2. Pathobiology and pathomechanics. PMID- 1296230 TI - Nonsurgical management of gallstones. AB - Nonsurgical management of gallstones has made considerable progress within the past 20 years. More than 95% of all patients with bile duct stones can be treated successfully by peroral endoscopic or percutaneous techniques. In the case of very large or impacted calculi, intracorporeal or extracorporeal lithotripsy is available (Figure 9-10). Mortality from these approaches is low (in the range of 1%) despite the fact that most patients are elderly and frail, and open surgery is rarely required. While nonsurgical management of bile duct stones is commonly accepted, there is disagreement as to whether gallbladder stones should be managed nonsurgically, especially in view of the introduction of laparoscopic cholecystectomy. For patients in good general health who are willing to undergo surgery, removal of the gallbladder is the treatment of choice. However, there are some patients in whom a nonsurgical procedure ought to be considered. These are patients with a patent cystic duct, a functioning gallbladder, and symptomatic, radiolucent stones who can be scheduled for elective treatment. In patients with small floating stones, solitary radiolucent stones or even multiple large stones with a CT density lower than 50 HU, the chance of complete clearance of the gallbladder ranges between 80% and 90% using oral dissolution therapy, direct contact dissolution, or a combination of extracorporeal lithotripsy and dissolution. Each method has its ideal candidates (Table 9-1). The overall percentage of patients with gallstones for these nonsurgical therapeutic options is probably not higher than 20%. Therefore, the impact on surgery is still minor. Controlled clinical comparisons of the different therapies are lacking at the moment. However, these approaches have already stimulated further research into the pathogenesis of gallbladder stone disease and will no doubt undergo further improvement. Drugs that, in addition to ursodeoxycholic acid, further reduce cholesterol saturation in bile such as 3-hydroxymethyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors are already under investigation for oral treatment of gallstones in combination with bile acids. Further studies will also clarify the influence of gallbladder motility and certain bile constituents, such as proteins, on clearance of gallstones and recurrence after successful nonsurgical management. Thus, nonsurgical options, which obviate the necessity for general anesthesia and eliminate the risk of bile duct injury, will certainly continue to play a role in the management of gallbladder stones. PMID- 1296231 TI - Ursodeoxycholic acid for the treatment of cholestatic diseases. PMID- 1296232 TI - The host immune response may be responsible for selection of envelope and precore/core variants of HBV. AB - The appearance of replication-competent variants of HBV with mutations in the envelope and precore/core proteins emphasizes that these proteins are the focus of immune selection pressure in the human host. The sequence and speed of application of the multiple selection pressures (humoral and possibly cellular) will determine the virological and clinical outcome. When these variant viruses are passed to a new host, in the absence of the immune selection pressures or modified immune pressures which resulted in their selection, a clinical picture different from that seen in the original host may emerge. Although HBV would seem to be highly evolved, it still seems to have the capacity for further diversity. A number of the reported variations have an obvious clinical relevance, but others do not, and further study is required to elucidate their importance. Whether they represent independently transmissible strains of HBV or are all selected during the course of infection, only to be lost in favor of the original strain on infection of another host, also remains to be determined. PMID- 1296233 TI - Cotranslational and posttranslational control of early steps in protein biogenesis: implications for the liver. PMID- 1296234 TI - Insulin resistance in liver disease and portal hypertension. PMID- 1296235 TI - Pathogenesis of sodium and water retention in liver disease. AB - The "Peripheral Arterial Vasodilation" hypothesis most completely explains the clinical spectrum of cirrhosis ranging from compensated to decompensated to the hepatorenal syndrome (Figure 15-1). As the systemic peripheral vasodilation increases, the neurohumoral responses to arterial underfilling are stimulated with resultant renal vasoconstriction, sodium and water retention. Hypoalbuminemia and portal hypertension, as well as local effects of vasodilation at the capillary level, also contribute to ascites formation and peripheral edema. The suppressed plasma renin activity and aldosterone concentrations and exaggerated natriuresis, which are observed in some patients with early cirrhosis during HWI and the supine position, probably indicate greater central translocation of splanchnic fluid in these volume expanded cirrhotic patients when compared with normal subjects. This interpretation is supported by the greater increases in ANF during HWI in these patients when compared with controls. The neurohumoral responses to arterial vasodilation in cirrhosis combine to decrease distal sodium and water delivery, an event which impairs escape from the sodium retaining effects of aldosterone and causes resistance to the distal tubular effect of ANF (Figure 15-3). As discussed, the peripheral arterial vasodilation of cirrhosis is no doubt multifactorial in nature and the resultant arterial underfilling may be worsened by events that could impair the cardiac response to afterload reduction, including bile salt accumulation, alcoholic cardiomyopathy, and tense ascites decreasing cardiac preload. This pathogenetic schema of cirrhosis is compatible with the unifying body fluid volume hypothesis (Figure 15-3), which we have recently proposed. PMID- 1296236 TI - Liver transplantation for fulminant hepatic failure. PMID- 1296237 TI - Molecular biology of the 2-oxo-acid dehydrogenase complexes and anti mitochondrial antibodies. AB - The confluence of molecular biology and clinical medicine has provided new and valuable insights in PBC. Our understanding of the immunobiology of PBC has changed dramatically using this new technology. It is now possible to explicitly define mitochondrial autoantigens and examine recognition sites, by using autoantibodies, at the primary sequence level. In addition, cloned antigens have been developed to reliably assay for presence of autoantibodies; the use of cloned recombinant antigens should replace that of traditional immunofluorescence for AMA assay. It is also now possible to begin the task of defining the role of T cells in the immunopathology of PBC and exploring the issue of whether immunotherapy is possible. Finally, there is increasing evidence that PDC-E2 is located on the cell membrane of biliary epithelial cells. The mechanism for this expression remains to be studied. The explosion of data in PBC is an example of the serendipity and synergy brought about by application of new techniques to investigate old problems. PMID- 1296238 TI - Biology of biliary epithelial cells. PMID- 1296239 TI - Vanishing bile duct disorders. PMID- 1296240 TI - [Results of liver examination in drug addicts infected with HIV virus]. AB - Investigations included 52 drug-addicts with asymptomatic HIV virus infection. 8 of them suffered some years ago, from virus hepatitis of type B. Physical examinations did not reveal in examined persons any deviations from normal condition except for hepatomegaly. Results of liver biochemical investigations remained within normal limits. In each of them one confirmed presence of serological markers of HBV infection and in 35 of them of HCV and in 5 of them in parallel HDV. In all the examined persons one carried out liver biopsy and routine morphological examinations. In every case one disclosed a liver injury of drug-induced type. Further, in 31 examined persons one detected a coexistence of chronic, active inflammatory process of liver hepatitis minimal--17 hepatitis chronica persistent--12 hepatitis chronica aggressivE--1 cirrhosis hepatis--1 and in four of them changes of the type fibrosis periportal. In HIV infected drug addicts it comes about to clinically asymptomatic, chronic hepatitis coexisting with morphological changes of drug-induced type liver. PMID- 1296241 TI - [Gastroduodenal reflux and histological changes in the gastric mucosa in patients with liver cirrhosis caused by HBV]. AB - Endoscopic and histologic examinations of the gastric mucosa were performed in a group of 35 patients with HBV liver cirrhosis and 30 healthy persons. From among the patients 2 groups were singled out according to a liver disease progression: cirrhosis during liver functional compensation (n - 20). Cirrhosis over the period of liver functional unbalance (n - 15). In the two groups of patients examined the authors found pathological changes in the gastric mucosa, those in the group of patients with liver functional unbalance being more frequent and progressed. A statistically significant relationship was found between the duodenal contents in the stomach and the appearance of inflammatory changes in the mucosa. PMID- 1296242 TI - [Is Aujeszky's disease a zoonosis?]. AB - Several cases of human illness with symptoms suggestive of Aujeszky's Disease (AD) at an outbreak of the disease in cattle and swine were evaluated during this study. Additionally serological studies of people in the group at high risk for illness caused by Aujeszky's Disease Virus (ADV) were carried out. In a herd of 180 bulls sudden clinical disease occurred with symptoms of muscular tremors, salivation, sweating and severe pruritus of the head. The clinical disease lasted two to eight hours and finished in death. In 7 days 10 bulls died and 60 were either killed or culled. A biological test for AD was positive. ADV was identified in the brain of a dead bull. Serological studies for the bulls were negative, however 92.9% on the premises farm were asymptomatically infected. On third to the fifth day of disease in the cattle clinical signs appeared in six of seven workers which had direct contact with diseased cattle. A pruritus of the palms, which spread onto the lower and upper arms, shoulders and back lasted several days. PMID- 1296243 TI - [Listeriosis--selected aspects of laboratory diagnosis and epidemiology]. AB - This review presents distribution of human listeriosis in the world including the large food-borne outbreaks in USA and Canada with the rising number of cases especially in Europe. Usefulness of food examination for L. monocytogenes is discussed. Methods for differentiation L. monocytogenes from other Listeria species and other genera are presented. PMID- 1296244 TI - [Trichinellosis focus resulting from consumption of wild boar meat]. AB - The focus of trichinellosis was presented comprising 28 patients and resulting from consumption of the wild boar meat. Early confirmation of trichinellosis diagnosis in the first case (index case) and an accurate epidemiological analysis established that the patients became infected with Trichinella spiralis strain originating from natural environment. A severe clinical course was disclosed in the index case, moderate course of trichinellosis in 11 patients, a mild course in 15 cases and an abortive course in one patient. The most frequent trichinellosis symptoms included muscular pain (92.3% cases), fever above 38 degrees C (62.2% cases), conjunctivitis (53.3%), periorbital and facial oedema (42.9% cases); headaches and excessive sweating were less frequent (35.8%), while diarrhoea, hemorrhages to the fingernail beds and skin rush were noted in single cases only. No leukocytosis was detected in 15 patients (53.5%) and number of acidophilic granulocytes was normal in 8 patients (28.5%) including 5 patients with moderate course of the disease. Also, no full correlation was detected between severity of the clinical course and anti-Trichinella antibody titres. Increased activity of a muscular enzymes creatine kinase (CPK) could be detected in 27 patients and increased activity of lactic acid dehydrogenase (LDH) in 9 patients. The increase in muscle enzyme activity (CPK in particular) in some patients failed to correlate with the severity of the clinical course. In 10 patients parasitological and histological study of muscle tissue biopsies was performed to determine intensity of the invasion and the character of pathomorphological lesions. PMID- 1296245 TI - [Complications imminent in patients with salmonellosis]. AB - In 1038 patients with salmonellosis treated in the last 20 years in Department of Infectious Diseases, Medical School, Bialystok and literature data defined, distribution and type of complications and consequences these diseases. In acute period of salmonellosis complications are: hypovolemic or infectious and toxic shock, metabolic acidosis, circulation collapse and ileus paralytic. As a late complications are mentioned organs changes and anemias. Salmonellosis nowadays may exist as a complications diseases with immunodeficiency (AIDS). PMID- 1296246 TI - [Qualifying individuals for vaccine against rabies and administration of the vaccine in Poland from 1980-1990]. AB - In Poland are implemented five basic elements necessary for the efficient human rabies control. They are: epidemiological surveillance of rabies; safe and immunogenic vaccine and serum; effective medical care; network of veterinary diagnostic laboratories; rabies legislation. Presented analysis is based on the 35,226 records of antirabies vaccinees in Poland during the period 1980-1990. It evaluates some failures in human antirabies control. The efforts to achieve the improvement in the standard of the performance should focus on the following: the most effective methods of increasing the level of public knowledge about rabies; medical postgraduated training in rabies; rapid methods for virus isolation; virological evidence (virus isolation) of infection in suspected atypical rabies hosts like squirrels, rodents, bats etc; pre-exposure vaccination for persons at risk of exposure. PMID- 1296247 TI - [Seroconversion after vaccine with trivalent influenza vaccine during the epidemic season 1990/1 in Poland]. AB - Vaccination was performed by influenza virus vaccine, trivalent type A and B. We vaccinated about 50,000 persons in Poland in different groups of age. HI and NI tests were used for testing antibody level for A/Taiwan/1/86 (H1N1), A/Shanghai/16/89 (H3N2) and B/Yamagata/16/89. The rise of antibody level was statistically significant. PMID- 1296249 TI - [Encephalitis during the course of measles]. AB - A case of measles encephalitis in a man aged 18 years was described. Attention is called to the relatively rare occurrence of such neurological complications in measles, diagnostic difficulties and good therapeutic results after corticosteroids and antiviral drugs. For reducing the incidence of measles and its neurological complications the author suggests the usefulness of protective re-vaccination against measles. PMID- 1296248 TI - [Evaluation of treatment outcome for bacterial meningitis and encephalitis at the provincial hospital of infectious diseases in Wroclaw during 1985-1989]. AB - Data about 848 patients treated in the years 1985-1989 in the Province Hospital of Infectious Diseases were analyzed. Among them were 98 patients with bacterial meningitis and encephalitis. The most frequent etiological agents were Neisseria meningitidis and Diplococcus pneumoniae. In none case Haemophilus influenzae was isolated. The average time of hospitalization was limited to 45 days. Treatment introduced at once was based on the results of bacteriological tests. Crystalline penicillin, cephalosporins of the II and the III generation and in some cases metronidazole were antibiotics of choice. Serious complications were observed in 25% of patients. 5% of patients died. PMID- 1296250 TI - [Tetanus in the Katowice district in the years 1976-1988]. AB - Analysis of 89 tetanus cases that appeared in Katowice district in years 1976 1988 in comparison with country data has been made. Morbidity rate was lower than country and frequency in younger age groups was lower too. About a half of dead ill persons suffered of injuries that was unusual for tetanus infections circumstances, and about a quarter of dead persons suffered only of slight and superficial trauma. Attention has been paid to frequent mistakes in specific prevention with injured persons. PMID- 1296251 TI - [Difficulties in diagnosing a case of typhoid fever]. AB - A sporadic case of typhoid fever of 41 years of age male was characterized clinically mainly with long duration of fever and a few enlargement of liver. Diagnosis was made relatively late. In this case an endoscopic picture of upper gastrointestinal tract and ultrasonographic findings of the organs of abdominal cavity was described. PMID- 1296252 TI - [Acute massive criminal arsenic poisoning. Epidemiologic examination--1990]. PMID- 1296253 TI - [Goiter in pre-school children from the Rzeszow district]. AB - The examination included 1594 children at the age of 3 to 6 from the city Rzeszow (834) and from villages in the Rzeszow district chosen at random (760). There were 865 boys (54.3%) and 729 girls (45.7%) in the group. The size of thyroid gland was measured according to the modified classification of WHO from 1974. All the examined children were in the clinical euthyroid state. Enlarged thyroid gland was found in 369 children (23.1%). Goiter OB was diagnosed in 271 children, I degree in 85, II degrees in 11, III degrees in 2. Enlargement of thyroid gland occurred significantly more often in rural areas (36.8%) than in towns (14.8%). The lowest percentage of goiter was found in 3-year-olds. These results point out that the province is an endemic area of mild goiter. Emphasis was put on the necessity to increase goiter prevention in the Rzeszow district. PMID- 1296255 TI - [Loneliness and its individual correlations with the degree of advancement of cerebral atheromatosis in old people in epidemiologic studies]. PMID- 1296254 TI - [Endemic goiter in the area of Mielec]. AB - The scope of this report is the incidence of goiter in school children living in Mielec and neighbouring villages. We examined a group of 3537 children aged 6-14. The enlargement of thyroid gland was observed in 49.3% of the population. Judging by the results of the research this region can be regarded as endemic. There might be several reasons for a high incidence of goiter in this region. The most important are: insufficient iodine prophylaxis, pollution of the environment including the pollution with radioiodine after the damage of the Chernobyl reactor. PMID- 1296256 TI - [Dr. Wladyslaw Prazmowski]. PMID- 1296257 TI - [Treatment of atypical mycobacterium infections: current state and therapeutic perspectives]. PMID- 1296258 TI - [Terminal care of patients with bronchial cancers]. PMID- 1296259 TI - [Diagnostic criteria, physiopathology and etiology of intra-alveolar hemorrhage]. AB - In the first part of this article the clinical and paraclinical criteria of intra alveolar haemorrhages are reviewed. The principal signs and symptoms are dyspnoea, haemoptysis, anaemia and bilateral alveolar and interstitial opacities. Computerized tomography of the chest shows a non-systematized alveolar filling. In the second part, the cytological and histological criteria are considered; they are provided by examination of the alveolar lavage fluid and by lung biopsy. Finally, the main elements in the physiopathology and causes of these haemorrhages are successively described. PMID- 1296260 TI - [External resistances and dyspnea. Value of the study of flow-volume loops]. AB - Breathlessness induced by external resistances (diaphragms with orifice size of 20, 15, 10, 7.5 and 5 mm) introduced in the ventilatory circuit of a spirometer and the corresponding parameters of a maximal flow-volume loop have been studied. 10 healthy subjects (5 men, 5 women), free from any acute or chronic cardiorespiratory disease, volunteered for this study. The results showed that the breathlessness (severe or moderate) was especially correlated with the decrease in peak flows, peak inspiratory flow (PIF) more than peak expiratory flow (PEF): when breathlessness was moderate, PIF was more decreased than PEF, 35% and -28% respectively; when breathlessness became severe, PIF also decreased more than PEF, -60% and -50% respectively; forced vital capacity (FVC) never changed and maximal expiratory flows at 50% and 25% of FVC were only slightly modified despite obvious breathlessness. The increase in diaphragmatic activity seemed more implicated than the activation of expiratory muscles in the genesis of breathlessness. PIF more than the commoner PEF could be a useful marker of the breathlessness perceived by the patient during acute bronchial obstruction (asthma). PMID- 1296261 TI - [Extrapleural hematoma: emergency diagnostic pitfall. Value of computerized x-ray tomography]. AB - A case of extrapleural haematoma consecutive to a chest injury is reported. This is a rare site of blood effusion since such injuries usually result in haemothorax. These two diagnosis can be distinguished not only by exploratory thoracotomy but also by computerized tomography which shows a characteristic subpleural fat-like ribbon. PMID- 1296262 TI - [Multiple nodular opacities in a young man]. PMID- 1296263 TI - [Endoscopic case: from diagnosis to therapy. Pseudotumoral pneumonia in broncholithiasis]. PMID- 1296264 TI - [Primary pulmonary candidiasis with favourable outcome. Apropos of a case]. PMID- 1296265 TI - [993.000.000.000.000 +/-?.000.000.000.000]. PMID- 1296266 TI - ["Soft" parameters and invisible resuscitation]. AB - Caring for a patient implies performing technical interventions and caring for the whole person, recognising his/her personal life, habits, family, wills. The working experience of an intensive care unit of Bellinzona is described: the theoretical framework that led the health team to start this new approach to intensive care patients and its translation in everyday practice. Verbal and non verbal communication skills (with the patient and the team) are pivotal in this approach; relatives are considered partners in the care of the patient and an essential element of the caring environment. Nurses identified meaningful data (soft data) related to living experience of the patient, to the interaction with the healing environment, his/her patterns of communication, and their use in the intensive care unit is described. PMID- 1296267 TI - [To live death in the hospital. The Lendinara School of Nursing]. AB - Issues related to death and dying are important subjects in the educational curriculum of nursing students; in the nursing school of Lendinara this subjects were discussed analysing practical and emotional experience of nursing students. An anonymous questionnaire was distributed to the 74 second and third year students (67 returned) to explore emotional experience and 52 terminal patients were observed during a 3 month period, to obtain data on the care of these patients in the hospital. Data were analysed by nursing students as part of their practical training. Some of the results are presented; results were discussed in the classroom and presented and commented in an open meeting with caring personnel (nurses, doctors, volunteers) involved in the care of dying patients. PMID- 1296268 TI - [The results of nursing interventions: is an evaluation possible?]. AB - The growing interest in measuring patients outcomes of nursing is argued has been occasioned by economic pressures and professionalizing thrust of the nursing profession. Problems in defining what a nursing intervention is and what can be considered an outcome are critically appraised. Ascertaining whether nursing care makes a difference by using outcome measures raises methodological as well as professional issues, for instance that of separating nursing from inputs of other professional groups. Opportunities and challenges posed to nurses by patient outcomes research are addressed, together with priorities for future nursing research in the field. PMID- 1296269 TI - [A window on the past: are women more adapted to care of the sick?]. AB - The issue of nurse and nursing as feminine concepts and profession was widely debated at the beginning of the century by various professional and political groups and female associations. One of the most accepted positions even among nurses was that women by nature are more patient and kind, therefore born to care for men. Women supported this position because saw in the nursing profession the possibility to have a job and economical independence, but the role of mother and nurse were considered conflicting. Doctors strongly favoured a female nurse, from middle class well educated women but the idea behind this position was to keep separate and subordinate roles. With the first World War, when lack of theoretical knowledge and organization of Italian nurses, especially compared with foreign countries, were evidenced, National Council of Italian Women proposed a nursing curriculum only for female nurses and with very strict requirements. Nurses Federation succeeded in 1920 in opening nursing education to both men and women but, with the advent of fascism, in 1925 a Regio Decreto Legge, with the establishment of Scuole Convitto only for female nurses was definitely approved. PMID- 1296270 TI - [Nursing research methods and instruments: an analysis of some articles]. AB - Research papers published on some of the most well known foreign nursing journals are presented and discussed. The main aim of the contribution, which opens a new arena for discussion on the Rivista dell'Infermiere is to critically appraise published research works focusing both on strengths and novelty and weaknesses in the hypothesis formulation, methods and instruments used, discussion of results. A critical analysis should enable nurses to start to learn to read and eventually write a research protocol, possibly avoiding some common mistakes. PMID- 1296271 TI - [The risk and prevention of deep venous thrombosis in hospitalized patients]. PMID- 1296272 TI - [Is it possible to prevent pulmonitis?]. PMID- 1296273 TI - [The living and health conditions of Palestinian children]. PMID- 1296274 TI - Clinical pathology for preclinical safety assessment: current global guidelines. AB - Regulatory guidelines for preclinical safety assessment studies of new drugs, chemicals, and food additives exist in many large industrial countries. Current guidelines include recommendations or requirements for clinical pathology testing. Many of the testing requirements are similar for every country, but others are not. The similarities and differences among several of the guidelines are discussed, and specific instances of ambiguous or inappropriate testing requirements are cited. PMID- 1296275 TI - Current statistical approaches to clinical pathological data from toxicological studies. PMID- 1296276 TI - Interpreting clinical laboratory data in safety assessment studies. AB - Traditionally, clinical laboratory data in safety assessment studies have been analyzed statistically to determine potential treatment-related effects. This has often led to inappropriate and/or controversial conclusions about clinical laboratory findings that are statistically significant but considered biologically unimportant. To overcome these problems, a decision-making process that integrates statistical analyses and sound medical judgement is required. Understanding the reasons why false-positive and false-negative results occur is the first step toward both better test selection and more accurate decisions on test material effects. PMID- 1296277 TI - Clinical pathology in the National Toxicology Program. AB - The National Toxicology Program (NTP) developed a standard approach for clinical pathology investigations that was integrated into most toxicity studies designed and conducted after 1986. Protocols for these studies include specific hematology and clinical chemistry analyses at 3 selected time points in 13-wk studies. Requirements concerning the anesthetization of animals, collection and analysis of samples, and reporting of results have been established to control sources of variability within and between contract laboratories that perform these studies for the NTP. Laboratories must meet minimum standards to be approved for participation in the Program. Important areas of consideration for these laboratories to perform clinical pathology investigations include the facility, equipment, personnel, performance, and quality control procedures. Clinical pathology results from approximately 60 13-wk studies that have been conducted by the NTP in 7 laboratories since 1987 are being analyzed to generate a database of control values for the Fischer rat and B6C3F1 mouse and to identify sources of variability. Experimental data from these studies are being analyzed and correlated with histopathologic findings to evaluate the contribution of clinical pathology to the characterization of toxicity and to examine the appropriateness of the current approach. Efforts such as these will provide for the evolution and continued relevance of clinical pathology in toxicity testing. PMID- 1296278 TI - Clinical pathology: preanalytical variation in preclinical safety assessment studies--effect on predictive value of analyte tests. AB - Significant differences in concentrations of analytes in samples may be introduced before samples enter analyzers. These differences are known as preanalytical variation and are part of the overall variation in analytical data. Preanalytical variation is caused by factors that operate during animal preparation prior to sampling, sample collection, sample processing, and sample storage prior to measurement. Preanalytical variation is important because it detracts from the predictive value of analyte measurements. Preanalytical variation may permanently damage data. Because its effects are difficult to quantitate it should be minimized in safety assessment studies. Sources of preanalytical variation are actions performed on animals prior to sample collection and actions performed on the specimen prior to analysis. Preanalytical variation produces a range of artefacts in experimental data. Consequences of preanalytical variation are loss of confidence in the data, obfuscation of real test article effects, false effects, and possibly the expense of repeating a study. To limit preanalytical variation, its sources must be identified, the effects documented, and measures devised to eliminate its sources. Predictive value (likelihood of actual disease) of appropriate clinical pathology tests in toxicology is inversely dependent on preanalytical variation: uncontrolled variation produces data with low predictive values, and controlled variation produces data with high predictive values. PMID- 1296279 TI - Enzymology in preclinical safety evaluation. AB - This short paper will briefly discuss the merits of determining plasma enzyme activities in pre-clinical safety evaluation. Emphasis is placed on the value of selecting the appropriate enzymes and collecting blood samples at the appropriate times during the study, so as to gain the maximum amount of diagnostic information. Examples of actual results will be cited to illustrate some of the points. These examples are drawn from the 2 commonly used toxicology species--the laboratory white rat and the beagle--and serve to demonstrate the importance of enzymology in monitoring the progress or resolution of an adverse drug effect. PMID- 1296280 TI - Clinical biochemistry requirements in the Organization for Economic Cooperation and Development guidelines--United Kingdom recommendations. PMID- 1296281 TI - Clinical pathology testing in preclinical safety assessment: regulatory concerns. PMID- 1296282 TI - The value of clinical chemistry data in animal screening studies for safety evaluation. PMID- 1296283 TI - Regulatory concerns in the current practices of clinical pathology. PMID- 1296284 TI - Regulatory concerns of the United States Environmental Protection Agency. AB - The US Environmental Protection Agency, under 2 of its legislative mandates, has the authority to require the testing of industrial and pesticide chemicals. Among the testing requirements, particularly in chronic studies, are those relating to hematology, clinical chemistry, and urinalysis. Some of these requirements will be discussed in detail. Comments on the usefulness of the current requirements and recommendations for changes will be solicited from the meeting participants. PMID- 1296285 TI - Thoughts on the proper use and interpretation of clinical pathology data in preclinical safety testing: a Canadian perspective. PMID- 1296286 TI - Present status of animal clinical pathology examinations in the Japanese Pharmaceutical Manufacturers Association. AB - This paper will review the current status of animal clinical pathology in Japan using data obtained during a survey conducted by the Japanese Pharmaceutical Manufacturers Association (JPMA). I am presenting this information as a representative of the Non-Clinical Evaluation Committee of the JPMA. Two co workers, Dr. Nomura of Daiichi Pharmaceutical Co., Ltd., and Dr. Unno of Kanebo Co., Ltd., are also involved in this effort. Investigating and discussing the various problems concerning animal clinical pathology is timely and truly heartening, and we expect this information exchange in the animal clinical pathology field to continue. PMID- 1296287 TI - Clinical pathology testing regulatory concerns. AB - In toxicity testing, each animal may have to be viewed as a surrogate for millions of people and should be examined as thoroughly as a human patient. However, there are many differences between human diagnosis and animal toxicity testing. Human diagnosis is primarily based on anamnesis, symptoms, and utilization of a huge database of diseases. However, in animal toxicity testing, clinical and anatomical pathology data are usually a primary source of toxicity information, even though the positive endpoints are generally not known in advance and the number of positive toxicity endpoints may be numerous. This situation will generate at least 2 practical problems in clinical pathology testing: (1) how to preselect test items without precise knowledge of toxicity endpoints and (2) how to handle multiple data sets for toxicity detection. The latter includes issues of inflation of the overall false-positive rate and multicomparison problems. A "disease" called "significantosis" and a concept of integrated interpretation of multiple biologically related items to avoid false positive judgments and unnecessary censoring of meaningful outlier data are briefly discussed. In general, toxicity tests are quite exploratory and the endpoints are unknown and multiple, so the procedures for data interpretation should be determined on a case-by-case basis. Construction of toxicity entity oriented databases may be a requirement for further refinement of toxicity study interpretation. PMID- 1296288 TI - Clinical pathology testing recommendations for nonclinical toxicity and safety studies. AACC-DACC/ASVCP Joint Task Force. AB - Clinical pathology testing in nonclinical toxicity and safety studies is an important part of safety assessment. In recent years, clinical laboratory testing has rapidly expanded and improved. Some government regulatory agencies provide guidelines for clinical pathology testing in nonclinical toxicity and safety studies. To improve these testing guidelines and the resultant safety assessments, the American Association for Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society for Veterinary Clinical Pathology formed a joint committee to provide expert recommendations for clinical pathology testing of laboratory species involved in subchronic and chronic nonclinical toxicity and safety studies. These recommendations include technical recommendations on blood collection techniques and hematology, serum chemistry, and urinalysis tests. PMID- 1296289 TI - [Physiopathology of intestinal Salmonella infection]. AB - Following a long period during which studies on the pathogenesis of salmonellosis and typhoid fever have been exclusively based on careful evaluation of clinicopathological data in infected patients and experimental infection in mice, the new tools that are now offered by molecular genetics and cell biology allow more systematic and analytical approaches. Numerous mutants have been obtained that can be assayed in selected cell assay systems such as in vitro-cultivated epithelial cells or macrophages, thus allowing to identify and characterize key virulence bacterial products as well as their eucaryotic receptors and effectors. Significant contributions have recently been made in the analysis of the mechanisms allowing invasion of the intestinal epithelium and survival and multiplication of bacteria within macrophages. However, many unsolved questions remain. It is still unclear what produces diarrhea during salmonellosis and studies on the pathogenesis of typhoid fever are still impaired by the lack of a proper animal model. PMID- 1296290 TI - [Resistance of Salmonella]. AB - The emergence and the increase of antibiotic resistant Salmonella particularly in non-typhi species has occurred in recent years. Beside plasmid mediated resistance, new resistance mechanisms like alterations of permeability have been identified. Factors associated with resistance are the use of antibiotics in human and animals. These findings have important public health implications. It seems necessary to define a more adapted policy in human and veterinary use in order to avoid the rapid emergence of drug-resistance among regularly active antibiotics like fluoroquinolones. PMID- 1296291 TI - [Epidemiology of minor salmonellosis]. AB - Epidemiological data concerning non Typhi salmonella infections in France and other industrialized countries are characterized by the important increase of S. enteritidis salmonellosis due to raw or insufficiently cooked eggs products since 1987, increase of salmonellosis among immunosuppressed patients, particularly patients with AIDS. There is a new interest for non typhi salmonellosis instead of typhoid fever which is regularly declining in industrialized countries. PMID- 1296292 TI - [Clinical aspects of salmonellosis]. AB - Salmonellosis includes two groups of diseases: typhoid fever and non-typhic infections. Epidemiological and clinical features are different in each group. Typhoid fever is a major health problem in developing countries. It realizes septicemia and endotoxinic symptoms, and has not to be forgotten when the patient is back from travelling. Non-typhic infections in most cases produce acute feverish diarrhea, conforming with collective food toxi-infection. Non digestive localizations are usually the fact of underlying diseases, and are able to kill the patient. PMID- 1296293 TI - [Non-typhoid salmonellosis in HIV infection]. AB - Non-typhoid Salmonella infections associated with HIV infection are 20 times more frequent than those observed in the general population. Drug addicts and homosexuals are equally infected. Concerning physiopathology, a deficit in gastric acid secretion has been blamed as an etiological factor, together with T cell deficit, except for reduction in the number of CD4 cells. This type of infection usually presents as fever; diarrhea is noted in only 20% of the cases. Several viscera can be involved. The best treatment seems to be fluoroquinones administered during 3 weeks, and several months in case of relapse. Patients under AZT therapy are less often affected with salmonellosis due to the antibiotic activity of this anti-retrovirus agent. PMID- 1296294 TI - [Salmonellosis: therapeutic aspects]. AB - The antibiotic therapy of salmonellosis has changed during the last decade, due to the development of resistance to classical drugs and also to increased knowledge in the conditions of in vitro and in vivo efficacy of new compounds. These new informations led to clinical studies of efficacy and tolerance of fluoroquinolones in the treatment of acute diarrhea or chronic carriage due to Salmonella, or against typhoid fever. These drugs appeared very efficacious and able to significantly shorten the duration of treatment. However, two potential pitfalls have to be kept in mind deserving additional informations: selection of resistant mutants and increased risk of persistent carriage. PMID- 1296295 TI - [Anti-typhoid vaccines]. AB - There are three commercially available vaccines against typhoid fever: parenteral inactivated whole cell vaccine, oral live attenuated (strain ty21a), parenteral polysaccharide vaccine (capsular antigen-Vi). Their protective efficacy is 50 to 88% (inactivated vaccine), 50 to 96% (live attenuated vaccine) and 75 to 80% (polysaccharide vaccine). The frequency of notable adverse reactions with the inactivated vaccine justifies the use of the new vaccines. PMID- 1296296 TI - [SVO2 catheter. A new method of monitoring in anesthesia and intensive care]. PMID- 1296297 TI - [Brief recurrent depression. A new severe form of depression]. PMID- 1296298 TI - [Bleeding time and hemorrhage risk. A simple test still in current use]. PMID- 1296299 TI - [Duodeno-pancreatic echoendoscopy. A major diagnostic tool]. PMID- 1296300 TI - [Phenylketonuria yesterday and today. Evaluation of the work of systematic neonatal screening]. AB - Phenylketonuria is due in the very great majority of cases to a deficiency in phenylalanine hydroxylase, an enzyme whose cofactor is biopterin. Prenatal screening consists in measuring the concentration of phenylalanine in a sample of dried blood taken after birth (levels are already raised by day 3). Screening, organized by the Association francaise pour le depistage et la prevention des handicaps de l'enfant, is very thorough (cover greater than 99%). Treatment involves observance of dietary restriction for at least five years. Results are good. Questions concerning the useful duration of dietary treatment, the level of phenylalanine that should not be exceeded, and the future of girls with PKU remain controversial. When adult, such girls may give birth to retarded children if they do not resume dietary restriction before becoming pregnant. Now that problems of screening, its organization, and the management of diet have been solved, these questions are the new challenge that faces us. PMID- 1296301 TI - [Tuberculosis, still yesterday ...]. PMID- 1296302 TI - [Colonic diverticulosis. Epidemiology, physiopathology, diagnosis, development, treatment]. PMID- 1296303 TI - [Hypoglycemia in children. Diagnostic orientation and emergency treatment with the dose]. PMID- 1296304 TI - [Autoimmune hemolytic anemia. Etiology, diagnosis, treatment]. PMID- 1296305 TI - [Dysphagia. Diagnostic orientation]. PMID- 1296306 TI - [Wound, contusion of the abdomen. Diagnostic orientation and emergency treatment]. PMID- 1296307 TI - [Cancer of the prostate. Diagnosis, development, prognosis, treatment]. PMID- 1296308 TI - [Cancer of the endometrium. Epidemiology, diagnosis, development, prognosis, treatment]. PMID- 1296309 TI - [Demential syndromes. Diagnostic orientation and treatment]. PMID- 1296310 TI - [Interpretation of an epidemiolog survey. Survey types, concepts of bias, causality]. PMID- 1296311 TI - [Cancer of the testicle. Pathological anatomy, diagnosis, development, prognosis, treatment]. PMID- 1296312 TI - [Epidemiology of asthma]. AB - Asthma epidemiology aims to provide answers to the following questions: what is the prevalence? what are the consequences? what are the risk factors of asthma? Questionnaires indicate that asthma prevalence averages 6 to 8% whereas assessment of bronchial reactivity reveals that approximately 15% of the population exhibit bronchial hyperesponsiveness; these figures have been increasing in many western countries. Asthma is an important cause of impairment in children physical development, school-related problems along with increased number and duration of hospitalizations. Asthma mortality averages 3/100,000 in France and is mainly focused on people more than 50 years old; its increase is very likely in some countries, but is still controversial in France. Environmental and socio-economic factors play a major role in the development of asthma and genetic factors are now under investigation. Although both understanding and drug treatment of asthma have dramatically improved in the recent past, no positive change has been observed so far in terms of morbidity and mortality. Nevertheless, knowledge of factors specific to France requires further investigations. PMID- 1296313 TI - [Physiopathology of asthma]. AB - Asthma is a multifactorial disease where genetic predisposition, environmental factors (allergens and pollutants) and endogenous factors intervene to varying degrees. Among the disturbances involved in the physiopathology of asthma dysfunction of the autonomic nervous system and development of bronchial inflammation are now known to play the major roles. From the adrenergic system, the role of which is now controverted, the attention of pharmacologists has shifted to the cholinergic central nervous system responsible for bronchial tone and the non adrenergic non cholinergic (NANC) nervous system. The more recently known NANC system is complex and mediated by neuropeptides, and it can alternately induce bronchodilatation and bronchoconstriction, as well as vasoconstriction and vasodilatation. The inhibitory NANC system acts through the bronchodilator VIP. The excitatory NANC system is mediated by tachykinins as which are potent bronchoconstrictors. Interaction of this system with the inflammatory cells induces a "neurogenic inflammation". Local inflammatory reaction is an almost constant element of asthma, irrespective of the cause of the disease. Although mast cells are the initial cells of the inflammatory reaction, there are important and complex cellular interactions with eosinophils, macrophages, lymphocytes and epithelial cells. Owing to their direct cytotoxic actions on the bronchial epithelium, eosinophils play a key-role in the inflammatory reaction. Cytokines secreted by alveolar macrophages, lymphocytes and mast cells amplify and maintain the inflammatory process. PMID- 1296314 TI - [From asthmatic crisis to severe acute asthma]. AB - Life-threatening acute attacks constitute the major complication of asthma. These attacks develop progressively or abruptly, within minutes. They are responsible for a mortality rate which in France has been estimated at 3 in 100,000 inhabitants. Most of the deaths occur before any medical assistance is given. Such deaths in serious attacks are caused by bronchial obstruction and not by possible cardiovascular complications. Since inflammation of the bronchi is now thought to be the primum movens of these near-fatal to fatal attacks, nothing but an early and prolonged anti-inflammatory treatment can prevent them. Because no precise profile of subjects at risk can be drawn, it is necessary to supervise with the utmost attention all patients who suffer from attacks of acute asthma which, unless proven otherwise, should be regarded as potentially serious: signs of severity must be systematically looked for, and strict therapeutic and monitoring measures must be taken. PMID- 1296315 TI - [Pseudo-asthma and asthma with hypereosinophilia]. AB - Despite of its high prevalence, asthma is not the sole cause of wheezing dyspnea: the obstruction of the principal airways, some diffuse bronchial diseases may present as pseudoasthma. The diagnosis of some behavioral dyspneas as well as functional laryngeal obstruction is sometimes highly difficult. The finding of a marked hypereosinophilia prompts the clinician to research a parasitic infection as a cause of pseudo-asthma, allergic bronchopulmonary aspergillosis complicating asthma, or an idiopathic hypereosinophilic disorder of which asthma is a component (as in Churg and Strauss syndrome). PMID- 1296316 TI - [Characteristics of allergic asthma]. AB - The frequency of extrinsic (or allergic) asthma varies with age and sex. An inborn tendency to atopy, shown by a positive Phadiatop test or by skin tests positive to air-borne allergens, is found in 50% of asthmatic patients. The arguments in favour of the allergic origin of asthma are primarily clinical: same time and place of symptoms in the typical form, frequent bouts of acute rhinitis, history of familial or personal atopy. The responsible allergen is often easily identified by questioning, and its nature can be confirmed by positive skin tests. The allergens most frequently involved are air-borne allergens, notably house dust mites furs or feathers of domesticated animals, and pollens. Compared with intrinsic asthma, extrinsic asthma has the following features: it begins at an earlier age, it is less severe, it seldom evolves towards chronic ventilatory impairment and, by definition, it implies that an allergen is responsible for the onset or worsening of the symptoms. PMID- 1296317 TI - [Asthma with permanent obstructive ventilation disorder]. AB - Asthma accompanied by chronic airways obstruction (CAO) is frequent and raises difficult clinical problems. Persistent inflammation of the airways is the main factor responsible for obstruction. There are no symptoms that distinguish this form of asthma from non-asthmatic chronic obstructive lung disease, and only respiratory function tests can confirm the diagnosis of CAO. Pharmacological tests with bronchodilators evaluate the bronchomotor part of CAO which is substantial in asthma as opposed to other causes of obstructive lung diseases. A negative test cannot exclude the diagnosis and suggests that the obstructive component due to bronchial inflammation is predominant. In such case a reversibility test performed with corticosteroids is of considerable interest as it reduces the partly reversible inflammatory part of the obstruction. Peak flow curves provide more precise date on the evolutive type of CAO and therefore contribute to a great extent to the monitoring and education of patients. Severe chronic asthma with high annual systemic corticosteroid consumption requires special care and justifies the current attempts made to replace corticosteroids by other anti-inflammatory drugs. PMID- 1296318 TI - [Non-allergen bronchial hyperexcitability and asthma: single and serial measurement]. AB - Non-specific bronchial hyperresponsiveness (NSBH) is an essential characteristic of asthma. Its absence in a symptomatic individual virtually excludes asthma. Its presence is not synonymous with asthma although, in the absence of other obstructive or restrictive pulmonary conditions, it strongly suggests the diagnosis. The severity of NSBH is related to the degree of bronchial inflammation. Changes in NSBH are more frequent, although not constant, in late asthmatic reactions. The measurement of NSBH is useful in confirming or excluding a clinical diagnosis of asthma. It can also help in assessing the need for medication. Serial assessment of NSBH can be a useful tool in the follow-up of an asthmatic subject or in a subject investigated for occupational asthma although figures for sensitivity and specificity are low and preclude its routine use in these circumstances. PMID- 1296319 TI - [The asthmatic child]. AB - Asthma is the most frequent chronic pediatric disease. Management is based on assessment of severity and should normalize lifestyle as well as pulmonary function. Mild asthma is treated with intermittent beta-2-agonists. Moderate asthma should receive non-steroids prophylactic anti-inflammatory drugs. Immunotherapy should be considered. Severe asthma requires inhaled steroids. At each stage inhaled medications should be preferred. Therefore inhalation delivery system must be adapted for children of different ages and degree of dyspnea. The importance of environment control is well recognized. Establishing a partnership with the child and its family and with the medical staff and with the child's school is always necessary. PMID- 1296320 TI - [Occupational asthma]. AB - The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, biological tests, respiratory function tests and non-specific tests of bronchial hyperreactivity and specific bronchial provocation test. The history search for the presence of an atopic state, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests run into the same snags. Respiratory function and non-specific bronchial provocation tests, confirm the diagnosis of asthma and enable the medium and long term prognostic to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen aerosols, realistic tests, and tests using exposure chambers to achieve true test doses. The products responsible for occupational asthma are multiple. The different substances are characterised in a simplified manner: first animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivates) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry. PMID- 1296321 TI - [Drugs for asthmatic crisis]. AB - The drugs used in asthmatic attacks must act on the two major mechanisms of the disease: bronchial obstruction and inflammation of the airways. Two main classes of drugs are available to reach these targets: bronchodilators, headed by beta 2 stimulants, and anti-inflammatory drugs of the corticosteroid family. Bronchodilatation obtained with beta 2-stimulants is the first and most effective treatment of the attack. These drugs are usually administered by inhalation: metered-dose aerosols with or without inhalation chambers, or nebulization for severe attacks. Very high doses can be used without fear of side-effects, the principal objective of this treatment being to relieve bronchial obstruction. In the absence of rapid and lasting improvement bronchodilators must always be combined with corticosteroids. In all cases medical supervision immediately after the attacks is necessary and the patient should subsequently be put under care of pneumologists. PMID- 1296322 TI - [Treatment of bronchial inflammation]. AB - Inflammation is a general defence mechanism. It is constant in asthma where it is characterized by the presence of eosinophils in sputum and blood. Treatment of bronchial inflammation is one of the master pieces of therapeutic strategy and relies on inhaled corticosteroids in most cases. These drugs are remarkably effective and can be used for long periods with little or no side-effects, but compliance with treatment must be checked regularly. In all cases, even when corticosteroids are the mainstay of maintenance treatment, bronchodilators must be used simultaneously. The triggering factors must be taken into account and re evaluated according to the course of the disease. In the short-term all efforts must concentrate on educating the patients and making sure that they comply with their treatment. In the mid-term new, more effective steroids with even less side effects than the others can be tried. In the long-term anti-inflammatory agents might multiply and be prescribed in combinations for successful cure of a multifactorial syndrome. PMID- 1296324 TI - [Huriet's law and clinical research. Some good, some less good...]. PMID- 1296323 TI - [Therapeutic strategy]. AB - The clinical manifestations of bronchial asthma fall into two categories: acute asthma which consists of asthmatic attacks and their variants, and chronic asthma. The treatment of acute asthma is now well established, while that of chronic asthma, more difficult to organize, is part of a true therapeutic strategy which has two aspects: 1. A more global approach to the treatment must be developed. This means full management of asthmatic patients who must be instructed and considered as active partners in the prevention of acute attacks, the evaluation of the severity of their disease and the application of the treatment prescribed. 2. An asthma severity scale must be devised and a specific therapeutic programme must be offered for each stage of the disease. The general principle, beside treatment of acute asthma, is to pay much attention to the intercritical situation and, in particular, to treat effectively the bronchial inflammation. PMID- 1296325 TI - [Nosocomial sinusitis in intensive care. A frequent complication that can be prevented]. PMID- 1296326 TI - [Fractures of the leg. Mechanism, diagnosis, treatment]. PMID- 1296327 TI - [Herpes zoster. Epidemiology, physiopathology, diagnosis, development, treatment]. PMID- 1296328 TI - [Complications of myocardial infarction. Diagnosis, development, treatment]. PMID- 1296329 TI - [Battered children. Diagnosis and management]. PMID- 1296330 TI - [Vomiting. Diagnostic orientation]. PMID- 1296331 TI - The T cell antigen receptor: biochemical aspects of signal transduction. PMID- 1296332 TI - The genetic basis of susceptibility to rheumatoid arthritis. PMID- 1296333 TI - [Recent progress and clinical significance of complement system]. PMID- 1296334 TI - [Physiopathology and therapy of pulmonary hypertension]. PMID- 1296336 TI - Social Security Bulletin. Annual statistical supplement, 1992. PMID- 1296335 TI - [Complications in patients with joint prosthesis--the cause, physiopathology and preventive methods]. PMID- 1296337 TI - Simulation of B-scan images from two-dimensional transducer arrays: Part I- Methods and quantitative contrast measurements. AB - Recently, theoretical investigations of the beamforming capability of two dimensional (2-D) transducer arrays have characterized the array parameters required to steer a symmetrically focused ultrasound beam up to 45 degrees off axis. These investigations have also shown that the number of elements in a steered 2-D array can be dramatically reduced by using a sparse set of elements, randomly distributed throughout the aperture of the transducer. The penalty paid for the use of a sparse array is the development of a "pedestal" sidelobe in the beam profile, the amplitude of which increases as the number of elements in the array decreases. In this paper the potential of 2-D arrays for medical imaging is assessed by simulating B-scan images of spherical lesions, both cystic and scattering, embedded in a large random scattering volume. Similar contrast characteristics over a range of cyst sizes are demonstrated for a dense 2-D array and a sparse array with 1/8th the number of elements, both operating at 5 MHz. A 32nd order sparse array is shown to perform at a reduced level, producing unacceptable artifactual echoes within images of cysts. The 8th order sparse array pattern has been fabricated on a fixed-focus poly(vinylidene difluoride) transducer using photolithographic techniques. Experimental images from this transducer are used to verify some of the theoretical predictions made in this paper. Comparisons between simulated B-scan images from linear and 2-D phased arrays are presented in a companion paper. PMID- 1296338 TI - Simulation of B-scan images from two-dimensional transducer arrays: Part II- Comparisons between linear and two-dimensional phased arrays. AB - Two-dimensional (2-D) arrays have been proposed as a solution to the degradation in medical ultrasound image quality occurring as a result of asymmetric focusing properties of linear phased array transducers. The 2-D phased transducer array is also capable of electronically steering the symmetrically focused ultrasound beam throughout a three-dimensional volume. In a companion paper the potential of 2-D transducer arrays for medical imaging has been investigated using simulated B scan images. In this paper, the advantages of 2-D over linear transducer arrays is demonstrated by simulating images of spherical cysts embedded in a large scattering volume. The large elevation beamwidth in the nearfield of a 5 MHz linear phased transducer array results in a severe reduction in the image contrast measured between a 4 mm diameter cyst and the surrounding scattering media. By employing a 2-D array with symmetric focusing, the contrast between the cyst and surrounding scatterers is significantly improved. The use of additional elements in the elevation direction of a linear array is also investigated. In this case the additional elements are included only to focus, but not to steer the ultrasound beam. Using the contrast characteristics of a 4 mm diameter cyst, it is shown that relatively few elevation elements are required to significantly improve the nearfield imaging capability of the linear array. PMID- 1296339 TI - Synthetic aperture imaging using a Lagrange based filtering technique. AB - Synthetic aperture imaging using a catheter based, circular phased array providing high resolution, dynamic focusing has been explored. Due to the high input impedance and low signal-to-noise ratio (SNR) of a classic single element synthetic aperture system, multi-element synthetic aperture processing has been proposed with SNR improvement of about 8 dB for a 33 element aperture. Reconstruction in this case uses an optimal filtering approach based on minimizing the mean square error between filter output and desired beam pattern. This approach, however, does not directly control both mainlobe beamwidth and sidelobe levels. To overcome this problem, a Lagrange based filter design technique has been developed that not only satisfies the minimum energy criterion, but also constrains sidelobe levels under a certain threshold. The new technique provides better spatial and contrast resolution. Both the mathematical formulation and simulation results are presented. PMID- 1296340 TI - A comparison method for mean frequency estimators for Doppler ultrasound. AB - Mean frequency estimators as used in pulsed Doppler ultrasound equipment should provide an accurate (quality) and consistent (robustness) estimate over a wide range of signal conditions. In a simplified signal model, the main parameters to consider are the noise level, mean frequency, bandwidth and power of both the Doppler signal and the stationary component over a given time window. It may be expected that one estimator for a given parameter combination exhibits a good performance while another estimator for the same parameter combination behaves poorly. To allow direct comparison between different types of frequency estimators, a method is introduced to evaluate the quality and robustness of estimators for a common signal space covering a wide range of realistic parameter combinations. The method is illustrated using three different mean frequency estimators: (1) a first order autoregressive estimator in combination with a stationary echo filter; (2) a second order autoregressive estimator; and (3) a complex linear regression estimator in combination with a stationary echo filter. It is concluded that, for the parameter combination considered, the complex linear regression estimator exhibits the best quality (low variance and bias of the estimate) and robustness (consistent quality for all parameter combinations). PMID- 1296341 TI - A discussion of two wavefront aberration correction procedures. AB - This review paper discusses the basic properties of two adaptive signal processing procedures for dealing with weak scattering in a phased array transducer system. A fundamental improvement in the lateral resolution of ultrasonic echo scanners will result if the weight vector of a large phased array transducer can be modified to account for distortion in the propagation medium. Lateral resolution in most tissue is limited to a few mm by wavefront-distortion induced sound-speed variations. One important wavefront-distortion source is scattering from local speed variations within large and reasonably homogeneous tissue beds such as the liver. Scattering disperses some energy from the beam and perturbs the wavefront, thereby distorting the image and limiting the resolution to the scale of the distortion. Often, such scattering is weak, meaning that most of the energy in the beam is unscattered. The total field at the receiving transducer is the vector sum of the unscattered and scattered fields. In weak scattering the unscattered field is dominant and the resultant field can be treated as the unscattered field plus a perturbation. The net effect is primarily a distorted phasefront, while the amplitude or modulus of the wavefront remains reasonably intact. Refraction and strong scattering effect the wavefront more severely and are less responsive to these algorithms. PMID- 1296342 TI - Two dimensional ultrasonic beam distortion in the breast: in vivo measurements and effects. AB - Two dimensional arrival time data was obtained for the propagation of ultrasound across the breasts of 7 female volunteers. These profiles were extracted through the use of cross-correlation measurements and a simulated annealing process that maintained phase closure while aligning the data. The phase aberration measured in two dimensions had a larger magnitude than previously reported phase aberration measured in one dimension in the breast. A point spread function generation computer program was used to demonstrate the system response degrading effects of the measured phase aberration and the usefulness of current one dimensional phase aberration correction techniques. The results indicate that two dimensional correction algorithms are necessary to restore the system performance losses due to phase aberration. PMID- 1296343 TI - [Pathogenesis of myocardial ischemia and acute coronary syndromes]. AB - Since the seventies, and in particular the eighties of this century, findings on pathogenetic mechanisms of ischaemic heart disease are expanding markedly and are becoming more accurate. This makes it possible to know and understand better factors which influence the genesis and development of myocardial ischaemia including the most serious clinical forms (unstable angina pectoris, acute myocardial infarction and sudden cardiac death). Diminution of the cardiac flow and/or increased oxygen demands of the heart muscle are not the only determinants of myocardial ischaemia which is influenced markedly also by neurohumoral, metabolic, prothrombotic (proaggregation and procoagulation) factors as well as antithrombotic and haemodynamic factors. Acute coronary syndromes have as a rule, in particular in patients with out severe atherosclerotic stenosis of the coronary arteries, a common pathophysiological mechanism of fissuration of the atherosclerotic plaque followed by different grades of dynamic coronary occlusion depending on vasoconstriction--spasm of the coronary arteries and thrombus formation. The coronary arteries, usually affected with atherosclerosis, may be due to the comprehensive action of various factors temporarily, intermittently or permanently occluded. In case of the development of acute coronary syndromes thrombosis plays a key role. Better knowledge of pathogenetic mechanism of IHD markedly changes views on treatment and management of patients with IHD in particular patients with acute coronary syndromes. The authors emphasize strategies focused (also preventively) on preventing progression of the disease with the aim to improve survival and the short-term and long-term prognosis. PMID- 1296344 TI - [Present views on unstable forms of ischemic coronary disease]. AB - The term unstable angina pectoris covers several forms of ischemic heart disease with heterogeneous pathophysiology, different clinical presentation and non uniform prognosis. Recent results of angiographic, angioscopic and autoptic observations on the nature of unstable coronary plaque rendered possible a better understanding of clinical symptoms of the unstable myocardial ischemia. Holter ECG monitoring of patients with unstable angina pectoris showed, that myocardial ischemia may persist despite the medical control of angina pectoris. It seems therefore more appropriate to use the terms unstable myocardial ischemia or unstable coronary syndromes rather than unstable angina pectoris. Coronary angiography in patients with unstable angina pectoris demonstrated eccentric narrowing with irregular or overhanging edges or intraluminal filling defects in 71-73% of vessels responsible for unstable myocardial ischemia. Autoptic studies showed, that thrombus usually develops on plaque with fissures, ulcerations and hemorrhage. The common pathway for all unstable coronary syndromes is an impairment of plaque integrity with subsequent activation of platelets, development of thrombosis and coronary spasm. Subsequent fate of coronary thrombus determines the clinical course with ischemic episodes lasting from several minutes to several hours. Medical therapy, PTCA or coronary bypass surgery are used to stabilise the patient, however, myocardial infarction or sudden death may occur. PMID- 1296345 TI - [Modern cardiac pacing. I. Dual-chamber pacemakers: 10 years' experience]. AB - Dual chamber cardiac pacemakers restoring an impaired atrioventricular synchrony meet a demand of contemporary so-called physiologic cardiac pacing. 39 dual chamber (DDD) pacers were implanted in 1982-1991 in our center. They improved both well-being and hemodynamic values (doppler echocardiography) more distinctly than common ventricular demand devices did. P-wave driven ventricular pacing in normal sinus node function (in 40 per cent of our DDD patients) made a frequency response in physical exercise possible. A short atrioventricular delay in DDD pacing proved to be helpful in the treatment for reentry tachycardias refractory to antiarrhythmic drug administration. Demanding implant, high price, lengthy programming as well as a higher incidence of complications (30.7 per cent) as compared to ventricular pacemakers (7.6 per cent) were the main problems of DDD ones. PMID- 1296346 TI - [Modern cardiac pacing. II. Rate responsive pacemakers: clinical experience]. AB - Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort are able to solve not only a bradycardia, but a chronotropic incompetence too. 23 rate responsive pulse generators, implanted in 1987-1991 in our center, simulated the physiological conditions and in this way they significantly improved both working capacity in bicycle stress test (p < 0.0001) and well-being in comparison with ordinary demand pacers. The incidence of complications did not exceed that in simple common pacemakers, but the rate adaptive ones were expensive and their programming was time consuming. In all three rate adaptive principles used their non-specific response revealed some imperfection of sensor driven devices. In addition, both in QT and in respiratory dependent systems their pretty proportional frequency response was delayed, while the irregular pacing rate in body activity sensor was not very proportionate to the physical exercise. The non-specific sensor response may be reduced by a combination of biologic sensors. PMID- 1296347 TI - [Relation between creatinine clearance and glomerular filtration in various stages of chronic renal disease]. AB - The relationship between creatinine clearance (Ccr) and inulin (C(in)) was investigated in 20 healthy subjects (group A) and 54 subjects with chronic renal disease (C(in): 10-80 ml/min/1.73 m2) treated conservatively (group B) and in 10 subjects with regular dialyzation treatment and a preserved residual diuresis (more than 1000 ml/24 h) (group C). In subjects from group B the Ccr/C(in) values were significantly higher than in healthy subjects (p < 0.01). In subjects of group C the values of Ccr/C(in) before dialysis did not differ significantly from values recorded in healthy subjects. Twelve hours after dialysis a marked increase of C(in)/Ccr occurred (p < 0.001). The findings are consistent with the idea that the increase of tubular creatinine secretion in patients with chronic renal disease is associated with a rise of its plasma concentration. In terminal stages in chronic renal failure there is, however, again a drop of tubular creatinine secretion which is reversible and rises after dialysis. These changes in tubular creatinine secretion could be explained by the fact that in chronic renal failure substances cumulate in the organism which inhibit tubular creatinine secretion. Due to haemodialysis the concentration of these inhibitors of creatinine secretion declines and after dialysis this process increases again temporarily. The findings suggest that the residual Ccr value assessed before dialysis is closer to the real value of glomerular filtration than values assessed during dialysis. PMID- 1296348 TI - [The effect of erythropoietin therapy on biocompatibility in hemodialysis]. AB - In order to evaluate the treatment with erythropoietin (EPO) on selected indicators of biocompatibility the authors examined 8 patients dialyzed for prolonged periods before treatment (HTK = 0.23, median), during EPO treatment (Recormon, administered by the s.c. route, HTK = 0.28) in the course of 4-hour haemodialysis on dialyzers with a Cuprophan membrane. The examination before and during treatment was made under equal conditions. Heparinization was also equal despite the fact that during EPO in four patients the residual blood volume in the dialyzer was increased. Comparison of the results before treatment and during EPO treatment did not reveal at any of the collection times (before dialysis, during the 15th, 10th, 60th and 235th minute of the procedure significant differences in the number of leucocytes, plasma concentrations of the C5a complement component, number of thrombocytes and activated coagulation times. Plasma concentrations of the thrombin-antithrombin III complex were in EPO during the 60th minute of haemodialysis significantly lower (p < 0.05) than before EPO. The authors conclude that EPO treatment does not have a significant effect on changes in the number of leucocytes in blood during haemodialysis nor on the activation of complement by an alternative way. EPO does not lead to a greater activation of the coagulation system during haemodialysis; the lower concentration of the thrombin-antithrombin III complex suggests the opposite. Explanation of this finding, similarly as detection of the cause of the increased residual blood volume in some patients, calls for further investigation. PMID- 1296349 TI - [Increased levels of noradrenaline in hypothyroidism and its association with cardiovascular system function]. AB - In a group of 10 athyroid subjects treated with thyroxine and triiodothyronine discontinuation of both hormones induced hypothyroidism. During its development on the 7th, 14th, 21st and 28th day systolic time intervals, the heart rate, blood pressure and noradrenaline and adrenaline plasma level were assessed. On the 7th day of hypothyroidism an increased index of the preejection time was recorded, and its value continued to rise throughout the investigation period. A reduction of the index value of the ejection time was also observed on the 7th day and during the subsequent period the value did not change any more. A decline of the heart rate was observed on the 7th day and subsequently the frequency was stable. The index of electromechanical systole was protracted on the 28th day. The systolic blood pressure declined on the 14th day and did not change afterwards. The diastolic pressure rose on the 28th day. The noradrenaline plasma level was elevated from the 21st day of hypothyroidism, the adrenaline level did not change during the decline of thyroid function. The authors discuss the mutual relationship of changes and evaluate the impact of the rise of the noradrenaline level in hypothyroid subjects. PMID- 1296350 TI - [Significance of laboratory examinations in the diagnosis of iron-deficiency anemia in older persons]. AB - In order to assess the effectiveness of selected laboratory examinations in the differential diagnosis of anaemias in elderly patients the authors examined 170 patients aged 65-93 years. Depending on the cause of anaemia, they divided the group into five sub-groups. Analysis revealed that for the diagnosis of iron deficiency anaemia the mean corpuscular volume and red cell haemoglobin level have a relatively low sensitivity (63 and 65.6%) and specificity (76.7 and 72.4%), serum iron has a very low specificity (37%) and the total iron binding capacity has a low sensitivity (31.3%). Serum ferritin (sF) has at the lower borderline of the reference interval 30 micrograms/l a 48% sensitivity and 100% specificity; when the value is 65 micrograms/l the respective values are 80 and 99%. Using routine parameters, it is not possible differentiate reliably in this group iron deficiency anaemia during chronic inflammations, infectious diseases and malignant diseases. Examination of SF when the lower borderline of the reference is raised improves the effectiveness of laboratory diagnosis in elderly patient. PMID- 1296351 TI - [Smoking habits of male and female physicians in the Czech Republic]. AB - The results of questionnaires given to 673 male and female physicians, pertaining to smoking habits, were compared with the Czech population with a similar age distribution according to results of the MONICA study. Male doctors smoke less frequently than men of the Czech population (24.2% vs. 44.9%). Female doctors smoke more frequently than male doctors, and what is worse, more frequently than women in the Czech population (27.4% vs. 26.6%). Specialists in internal medicine smoke least frequently (17.4%), surgeons smoke most frequently (32.3%). Partners of male and female smokers smoke more frequently than partners of non-smokers. Husbands more frequently than wives. Smokers are more frequently ignorant of their other risk factors. The authors present also data from some European and overseas countries. In countries where the number of smokers among medical doctors declines, there is also a decline of smoking in the general population. In the USA, Great Britain, Switzerland, Norway and Sweden smoking habits declined among physicians during the past 30 years 3-6x. PMID- 1296352 TI - [Treatment of congestive heart failure using angiotensin I convertase inhibitors]. AB - The authors describe the case of a 70-year-old female patient with ischaemic heart disease with an implanted pacemaker on account of sick-sinus syndrome, who after classical treatment with diuretics and cardiotonics suffered from frequent relapses of global decompensation of the circulation. After administration of the ACE inhibitor--Tensiomin--within a very short time (days) normalization of all indicators of previously severe congestion was found. During the subsequent follow up no relapse of decompensation occurred. The patient was shifted from stage IV to stage II in the functional classification of ischaemic heart disease according to NYHA. PMID- 1296353 TI - [Adult-onset Still's disease--the effect of methylprednisolone pulse therapy]. AB - The authors describe in a 40-year-old woman Still's disease with an adult onset. The activity of the disease was not controlled by large Prednisone doses and therefore pulsed treatment with methylprednisolone with very favourable results was used. The authors discuss the use of pulsed treatment with methylprednisolone in this disease. PMID- 1296354 TI - [The lipid metabolic indices in hypertensive patients under a plant fat load]. PMID- 1296355 TI - [The effect of linseed oil on the fatty acid composition of blood plasma low- and very low-density lipoproteins and cholesterol in diabetics]. AB - Twenty patients with compensated diabetes mellitus of 10-15-year duration took polyunsaturated fatty acids omega-3 (30 g of flax oil a day) in addition to their routine food. This led to an insignificant lowering in total cholesterol and elevation of cholesterol in high density lipoproteins. A significant rise in the level of omega-3 polyunsaturated fatty acids in lipoproteins occurred in 6 patients only. Minor effect of the diet oil may be due to low delta-6-desaturic activity in the majority of the examinees. The findings point to necessity to use other sources of omega-3 acids in diet therapy of diabetics, fish oil, in particular. PMID- 1296356 TI - [The effect of omega-3 polyunsaturated fatty acids on the clinico-biochemical indices and kidney nitrogen-excreting function in patients with chronic kidney failure]. AB - The addition of fish oil (20 g for 3 weeks) to diets of 7 patients with chronic renal failure (CRF) contributed to correction of metabolic derangement and nitrogen release, to alleviation of clinical symptoms. The most pronounced positive shifts were reported in early CRF. This gives evidence for a preventive value of diets supplemented with fish oil which secure delay of terminal CRF. PMID- 1296357 TI - [The use of monosodium glutamate in the combined therapy of patients with atrophic gastritis]. AB - Monosodium glutamate (MSG) taken per os has been found to stimulate gastric secretion provoked by pentagastrin. MSG gave rise to a marked elevation of endogenic gastrin levels both in experimental animals and atrophic gastritis patients. Thirty-six patients with secretory gastric insufficiency received MSG as an additive to their food during combined therapy of their disease. The preparation proved to be well-tolerated, good stimulant of gastric secretion, efficient in digestion improvement. MSG is recommended as an adjuvant in combined therapy of atrophic gastritis. PMID- 1296358 TI - [The alimentary correction of dyslipoproteinemias in children with a hereditary risk for ischemic heart disease]. PMID- 1296359 TI - [The vitamin C, B12 and folate allowances of pregnant women in Moscow]. AB - A dietary supply of vitamins was studied in 212 pregnant women for 11 months. Mean blood levels of vitamins were found subnormal, the percentage of the women with vitamin deficiency increased. Especially inadequate was supply of folate followed by vitamin C. Intake of 1 dragee a day of polyvitamins "Gendevitum" improved the vitamin status of the examinees with the best results obtained in the first trimester. Folate and B12 levels decreased with advance of pregnancy irrespective of polyvitamins administration. Vitamin C supply was better in summer and autumn, folate levels were higher in winter and spring. It is suggested that vitamins C, B12 and folate deficiency observed in pregnancy should be corrected. PMID- 1296360 TI - [The evaluation of the efficacy of a 6-month vitaminization of schoolchildren in grades 1 to 8 in the city of Baku]. AB - Investigations were conducted in 110 schoolchildren aged 7-10 and 11-14 years. They had received insufficiently balanced traditional nutrition deficient in animal proteins, vegetable oils, calcium, and, especially, in vitamins. Excretion of ascorbic acid, thiamine, riboflavine, N1-HA was decreased as compared to the lower standard limits 3.5-1.9 times in 85-90% of schoolchildren aged 7-14 years, microsymptoms of vitamin deficiency (including polyvitamin deficiency) were noted in 33-53% of the children. Administration of varying doses of "Undevitum" (0.5, 1 and 1.5 dragees/day) has shown that for normalization of vitamin status, decreasing morbidity rate and improvement of their mental capacity, the schoolchildren of 1-4 forms should receive 1 dragee and those of 5-8 forms--1.5 dragee of "Undevitum"/day as an optimum dose. PMID- 1296361 TI - [The vitamin allowance of the pupils in a rural vocational and technical school and their prophylactic vitaminization]. AB - The actual nutrition and providing with vitamins C and B1 was studied in boys aged 16-17 years, students of a rural trade school (Volsk of Saratov Province). Although the caloric value of their ration was high enough the content of animal proteins was only 42-48 g/day. The content of ascorbic acid in the ration comprised 48%, in the spring of 1987 it was 17%, and of 1988-29% of the recommended standard, vitamin B1 levels did not show seasonal differences. Vitamin C and B1 deficiencies in the spring were proved by their low excretion levels in urine, and by a low concentration of vitamin C and decreased activity of B1-dependent enzyme transketolase in the blood. Intake of "Undevitum" (1 dragee/day) during 4 months was conductive to the improvement of the student providing with vitamins. PMID- 1296362 TI - [The effect of the multivitamin premix 730/4 on the vitamin C allowance, physical development, work capacity and psychomotor indices of athletes]. PMID- 1296363 TI - [The effect of milk consumption on the activity of the formaldehyde detoxification system in sensitization to this compound]. AB - The activity of formaldehyde dehydrogenase (FDG) and total nonspecific formaldehyde oxidative activity of nasal mucosa and liver and the amount of reduced glutathione in the liver were measured in guinea pig subjected to epicutaneous or inhalative action of formaldehyde and additionally fed with cow milk. Glutathione-deficient animals demonstrated an increase in FDG activity following formaldehyde sensitization both in the liver and in nasal mucosa, whereas FDG activity in glutathione-supplied animals did not change significantly. The concentration of formaldehyde in the internal environment is supposed to be controlled by the levels of coenzyme (reduced glutathione) and FDG activity. PMID- 1296364 TI - [The characteristics of the involvement of the islets of Langerhans in rats with alloxan diabetes on rations with a varying quota of protein]. PMID- 1296365 TI - [The comparative activity of natural and synthetic enterosorbents in experimental hyperlipidemia]. AB - In-vitro experiments have shown that dietary fibre microcrystalline cellulose and lignin (polyphepan) possess high activity in binding sodium salt of cholic acid. This action is comparable with that of pectin and metamucile. Hypolipidemic effect of microcrystalline cellulose, polyphepan and synthetic enterosorbents carbonates was also seen in hyperlipidemic rats. It is concluded that microcrystalline cellulose and polyphepan hold promise as a dietary supplement for hyperlipidemic patients. PMID- 1296366 TI - [The level of available methionine and the biological value of fish protein]. AB - Food value of fish protein in fish canning was evaluated biologically and chemically (by available methionine). High-temperature sterilization (126 degrees) proved the least adequate for it causes the greatest loss in the protein food value. The chemical method by available methionine showing close correlation with biological techniques (NPU and PER rates) is thought demonstrative and convenient for technological control in fish processing industry. PMID- 1296367 TI - [Triacylglycerols in human milk and milk mixtures for infant feeding]. AB - High-performance liquid chromatography and computer program for identification of individual triacylglycerols (TAG) were employed for investigation of TAG composition of mature breast milk and 8 specimens of dry milk food for infants. The comparison was made by 15 molecular types of breast milk TAG using methods "close neighbour" and "star symbol plot" (Statgraphics). The composition appeared quite different. The design of artificial nutrition for infants basing on identity of fatty acids is believed inadequate as it cannot reproduce Tag composition of natural breast milk. PMID- 1296368 TI - [The effect of excessive ascorbic acid consumption on the body allowance of mineral elements]. PMID- 1296369 TI - [The use of ferrocyanides for obtaining pure meat production in contaminated areas following the accident at the Chernobyl Atomic Electric Power Station]. AB - The paper reports a new technique of obtaining radioactive Cs-free meat in the regions contaminated with radionuclides as a result of Chernobyl accident. The method is based on specific digestion features of ruminant animals. Ferriferrocyanide compounds are proposed as sorbents. Ferrocene is most efficient when introduced into mixed feed (1-3 g/day for sheep, 3-5 g/day for calves and young bulls) once a day. After that the animals can be fed radioactively contaminated forage and graze on contaminated land. PMID- 1296371 TI - [The mineral substance content of food products in eastern Kazakhstan]. PMID- 1296370 TI - [The nitrate reductase activity of human saliva]. AB - Investigations of human saliva reductase activity report the enzyme inactivation in 5-min heating at 50 degrees C, its maximal activity in neutral medium, reduced specific activity in the saliva dilution. Routine centrifugation inactivated nitrate reductase in supernatant, its activity in the precipitate hardly reached 10%. Combination of supernatant with precipitate recovered the baseline activity completely. Nitrates reduction into nitrites requires donor electrons. The latter are suggested to be present in the supernatant. Dehydrogenases substrates (lactate, pyruvate, malate, etc.) may act as donor electrons for nitrate reductase reaction. The addition of lithium lactate instead of supernatant to the precipitate partially recovered nitrate reductase activity. Biological role of salivary nitrate reductase is considered. PMID- 1296372 TI - [The content of amino acids in watermelon pulp]. PMID- 1296373 TI - [Experience in organizing medical examinations and scientific observation in conducting the vitaminization of schoolchildren in Krasnoyarsk]. PMID- 1296374 TI - [A case of histamine poisoning related to the consumption of Iwashi preserved herring]. PMID- 1296375 TI - [Overt and latent restlessness and the awareness of the meaning of life in patients with valvular heart disease]. AB - By means of R. B. Cattell Self-Knowledge Sheet and Crumbough and Miholick Scale of the Awareness of the Meaning of Life, 25 patients were examined, prepared for surgical correction of valvular heart disease. By means of R.B. Cattell Self Knowledge Sheet a group was isolated of patients showing high overt restlessness (OR) and high latent restlessness (LR). It was shown that the personalities of these two groups of patients demonstrated numerous common features, but very significant differences also existed. The patients with high latent restlessness (LR) demonstrated strong emotional tension caused by frustration, feeling of inferiority with low self-estimation, as well as many conflicts at super ego level, but they had strong defensive mechanisms of own personality. The patients with high overt restlessness (OR) revealed high degree of intensification of the feeling of isolation, loneliness, and existential emptiness resulting from the lost feeling of the meaning of further existence with the progress of disease. The results of our studies are guidelines for the choice of psychotherapeutic management of patients qualified for operation of valvular heart disease. PMID- 1296376 TI - [Arteriovenous fistula with subcutaneous displacement of basilic vein in children left in a program of repeated hemodialysis]. AB - In the paper 15 children are presented with terminal renal insufficiency in whom 17 arteriovenous fistulas were created between brachial artery and basilic vein displaced subcutaneously within the arm. Operational technique and obtained results are discussed with particular stress put on the usefulness of this type of fistula for children requiring treatment with haemodialysis. PMID- 1296377 TI - [Appearance of circulating immune complexes in patients with Hodgkin's disease and the etiology of this disease]. AB - The serum of 47 previously untreated patients with Hodgkin disease (HD) was subjected to analysis for the presence and level of circulating immune complexes (IC) detected by the tests of inhibition of EA and EAC rosette formation. The control group included 100 healthy persons, health service workers. Significantly higher incidence and levels were demonstrated of EA IC and EAC IC in the serum of patients in relation to the control group (p < 0.001). No correlation, however, was found between the appearance of EA IC and EAC IC and the degree of clinical progression of the disease, and the presence or absence of systemic symptoms. The presence of IC in the serum of patients with HD is one link in the whole chain of various immunological disturbances existing in this disease, the starting point of which can be a pathologically changed cell of the lymphatic system. PMID- 1296378 TI - [The effect of diet on the concentration of fructosamine in the serum of obese people]. AB - The influence was studied of slimming diet on the concentration of fructosamine in the serum of obese persons with normal glucose tolerance. It was found that the reduction of carbohydrate supply, apart from body weight reduction, led to normalization of the raised fructosamine level. PMID- 1296379 TI - [Ultrasonographic criteria of diagnosing tubal pregnancy]. AB - The results were subjected to analysis of USG examination of 11 patients with tubal pregnancy, verifying the found echographic anomalies with the intraoperative assessment done shortly after the USG examination. Of greatest usefulness for the preoperative diagnosis of tubal pregnancy is, according to the authors' opinion, coexistence of the following sonographic signs: enlargement of the uterus without echographic sing of pregnancy in the uterine cavity;-a mass of irregular outline, cystic-solid appearance, and axial dimension of above 50 mm, situated near the uterus;-fluid in the Douglas pouch. The experience of the authors shows that ultrasonography is a valuable supplementation of clinical examination and laboratory analysis in the diagnosis of tubal pregnancy, on condition of using objective criteria for sonogram interpretation. PMID- 1296380 TI - [Homocystinemia--a risk factor for atherosclerosis]. PMID- 1296381 TI - [Functional and morphologic changes of left ventricular myocardium in the course of aortic valve disease]. AB - The mortality of patients with aortic valve disease is growing significantly from the time of manifestation of features of left ventricular heart failure. Probably, the causes of that situation are the irreversible changes in the myocardium. During the first, asymptomatic stage of aortic valve disease, the increase of preload and afterload is compensated by myocardial hypertrophy, concentric or eccentric respectively. The global heart function as a pump remains normal, in spite of decreased contractility of individual sarcomeres. Valve replacement at that stage of the disease gives the best effects, being the causal treatment. After having used up the compensation possibilities, of the myocardium, the features develop of left ventricular heart failure. The mortality of patients operated on in that stage of the disease is high. Valve replacement is often a palliative method. PMID- 1296382 TI - [Sudden death--aspects of epidemiology and prophylaxis]. AB - The survey of literature is presented from the last over ten years, pertinent to the ever present problem--sudden death. The paper presents mainly the problems of epidemiology, and the possibilities and methods of preventing sudden death, as well as the organizational activities increasing the chances of resuscitation of patients with sudden cardiac arrest. PMID- 1296383 TI - [Pharmacologic treatment of atrial fibrillation in patients with Wolff-Parkinson White syndrome]. PMID- 1296384 TI - [Genetic counseling in the case of carrier state with reciprocal chromosome translocations]. AB - The principles are presented of genetic counselling for families with carrier state of reciprocal chromosome translocations (RCT). RCTs are the risk factor for the occurrence of reproduction disturbances, such as infertility, spontaneous abortion, congenital anomalies in the offsprings, and the degree of risk depends to a large extent on which chromosome segments are in the state of imbalance in the offsprings, due to various mechanisms of abnormal meiotic segregation. The uniqueness of chromosome translocations with respect to the type of chromosomes involved in translocations, and the location of breaking sites is the reason for the necessity of construing large pedigrees for the evaluation of the degree of risk. The newest Stene and Stengel-Rutkowski model makes possible the combination of smaller pedigrees in translocation groups of the so-called single risk of imbalance and determination of the individual risk of birth of children with anomalies. A number of psychological determinants are important for the possibility of genetic investigations in the affected families, and the decision about procreation may be influenced by a number of determinants other than the result of genetic counsel. PMID- 1296385 TI - [Difficulties diagnosing type I distal tubular acidosis in a 10-year old girl]. AB - A case is presented of type I distal tubular acidosis in a 10-year-old girl. The characteristic features of the disease are discussed together with related difficulties in the diagnosis of this case. The attention is paid to the age of diagnosis establishing, and to the clinical consequences resulting from the administered appropriate treatment. PMID- 1296386 TI - [Foreign bodies of the bronchus in children]. PMID- 1296387 TI - [A case of hypothyroidism with ascites as the dominant symptom]. PMID- 1296388 TI - [A case of functional hyperprolactinemia]. AB - A case is presented of a 27-year-old woman in whom galactorrhoea and amenorrhoea occurred simultaneously with the signs of acute neurosis. The determination of prolactin concentration after the administration of metoclopramide made possible the diagnosis of functional hyperprolactinaemia. Other causes of hyperprolactinaemia were excluded. The signs and symptoms regressed completely after several months of treatment with parlodel. Control investigation done after 18 months showed that the concentration of prolactin after administration of metoclopramide was slightly lower than before, but was still high. PMID- 1296389 TI - [Duodenal neurofibroma as a cause of chronic bleeding from the gastrointestinal tract]. AB - A rare case of chronic exacerbating gastrointestinal tract bleeding is reported which was caused by duodenal neurofibroma. The patient was successfully treated surgically. PMID- 1296390 TI - [Primary thrombocytosis causing profuse abdominal bleeding from a ruptured graafian follicle]. PMID- 1296391 TI - [Restriction or fulfillment. Ethical topics on suicide and sexuality of the elderly]. PMID- 1296392 TI - ["I want to join my Peterle". Anthropological and ethical considerations of sexuality and suicidal behavior in the elderly]. AB - Sexuality and suicidality express man being competent to shape his/her own life. From the bioethical point of view both phenomena are connected by shortening and fulfilling as well as autonomy. Considerations are provided for the physician to assist the aged being competent. Adequate framework is related to a concept of values guide living together. Thus tenderness and communication are appropriate levels of sexuality. Therefore they are to be integrated into the physician's concept of sexuality. For suicidality that means not to rescue life in a biological sense, but helping the elderly people making their life fulfilled and determining their life competent. PMID- 1296393 TI - [Sexuality and suicidal behavior. Ethical considerations from the viewpoint of geriatrics]. AB - The alternative "restriction" or "fulfillment" characterizes as age as geriatrics. Necessarily geriatric medicine has to realize not only a holistic concept of medicine but also to deal with the ethic questions and tasks risen by this quest. In both regards completion of awareness of the patient and his background is central. Especially concerning sexuality and suicidality geriatric and ethic interest must focus on the patient and his subjectivity and not start abstractly from principles and norms. PMID- 1296395 TI - [Hermeneutics of the quality of life concept]. AB - Medicine looks for reasonable criteria solving the problem of fair allocation of resources, assessing risks or discontinuing treatment. Further a reasonable measure is required for treating or accepting life in a reduced stage. The term "quality of life" seems to be like that. But it is generated by social politics and its problem, i.e. what people need for living, and does not ask whether a special treatment is useful for a patient. Thus the term should be used as follows: 1) only from patient's perspective, 2) as an undefinable term related to an "anthropologia negativa", and 3) reconstructing patient's preferences. PMID- 1296394 TI - [Quality of life--discourse and dialogue of a multilevel concept]. PMID- 1296396 TI - [The quality-of-life doctrine and the sanctity of life]. AB - The term "quality of life" might be used to qualify external circumstances with regard to the life of human beings (A). It also can be used to define the quality of a human life itself (B). Then it replaces the idea of "sanctity of life" by an eugenic idea that can be abused as a notion of discrimination. The B-position implies that life is only an instrument in order to serve a separable purpose (i.e. "the quality of being a person"). This specific quality articulates itself in so-called "indicators of humanhood/personhood". In consequence this "quality" is an eugenic expression including a dangerous power of definition and a selective anthropology that does not seem to be convincing theoretically and that can never serve as the basis of a reasonable and good social life of man. PMID- 1296397 TI - [Quality of life and fate]. AB - While the term "happiness of life", the "eudaimonia" of the greek philosophers, includes the good as such and therefore a metaphysical and moral component, the modern term of the "quality of life" is wholly defined by the criteria of a person's functional capacity and subjective wellbeing. The doctor's orientation by these criteria meets its limits, where he is confronted with fatality. This shows that we cannot really comprehend the quality of life without man's fundamental task of mastering his fate. PMID- 1296398 TI - [Quality of life--demands and reality as a medical parameter versus quality of life as individual reality]. AB - Quality of life (QL) is a term, whose definition extends beyond scientific methods. Even the most accurate description will only be able to represent a part of the reality due to the proviso of only a limited view. For that reason the abandonment of this term, described as "utopical" and "principally remaining in dissent", was called for. This could be countered by the possibilities to use QL as a therapeutic aim, as well as an aid towards finding an individual indication. Alone the demand staged by QL, to take the individuality seriously, and to be the motor for patient oriented medicine, make this term valuable. The definition itself will remain a called instruments have been developed and tuned, their evaluation has not yet been concluded. The acceptance of QL-registration within clinical studies is low, since the individual integration of values compared to the biometric difficulties can hardly be generalized. The aims of QL-research are: the individual focus on the field of projection of QL; a motivation-oriented mode of record; the involvement of QL-registration in form of information and accompaniment; adequate modular techniques including dialogical methods (nondirective interviews); the establishment of a QL-anamnesis towards an extension of the clinical picture; the observance of a possible conflict of roles, the danger of linguistic inaccuracies and misunderstandings, the consideration of a person's privacy. PMID- 1296399 TI - [Type I diabetes mellitus: quality of life as a subjective reality in the systemic context]. AB - Quality of life of insulin-dependent diabetics seems to be redefinable because of new findings in diabetology, i.e. more flexible therapy-concepts. Objective quality of life--operationalized by metabolic parameters--stands against subjective assessment by the patient. A comprehensive model of subjective quality of life-assessment of type-I-diabetics is presented. Beside individual assessment processes also systemic factors are integrated. Finally, consequences for diabetes-care are discussed. PMID- 1296400 TI - [The "dialogic principle" as the force of the physician-patient relationship]. AB - The discussion is opened with an analysis of the inherent problems of the concept of quality of life. Why must it be pressed into the straight jacket of a quantitative scheme? The second theme, the thesis that verbal contact and interviews in the doctor's office are an application of the philosophical programme of personalism and "dialogism", is also critically analyzed. Why must the physician (and the psychotherapist) aim so high? Is not the lack of symmetry between the physician and the patient typical of the verbal contact between the two? These factors are discussed, not-withstanding the valid insight that intense personal concern and contact are highly desirable in patient-oriented medicine. PMID- 1296401 TI - [The dialogic principle in medical treatment]. AB - Almost all kinds of medical therapy are based on a therapeutical dialogue. Some aspects of the dialogue principle in medical therapy are shown in this article. In addition the dialogue can open ways of communication to art-therapy (e.g. music therapy) and even to the arts itself. PMID- 1296402 TI - [6th Heymans Memorial Lecture. The significance for medicine of basic medical biological research]. PMID- 1296403 TI - [Organization and financing of biomedical research: national and regional aspects]. PMID- 1296404 TI - [European vision]. PMID- 1296406 TI - [Science policy in Flanders]. PMID- 1296405 TI - [Biomedical research: cost-benefit analysis]. PMID- 1296407 TI - [University education is more than higher education]. PMID- 1296408 TI - [Biomedical scientific research at the university]. PMID- 1296409 TI - [Evaluation of fundamental research]. PMID- 1296410 TI - [Education, status and future of the researcher]. PMID- 1296411 TI - [Medical faculties and university hospitals, partners in biomedical scientific research]. PMID- 1296412 TI - [Strengths of the Foundation for Scientific Research]. PMID- 1296413 TI - [The work environment of the biomedical researcher]. PMID- 1296414 TI - [Forms of cooperation between industry and university]. PMID- 1296415 TI - The changing pattern of measles in Papua New Guinea--past and future. PMID- 1296416 TI - There should be a place for emergency public health in Papua New Guinea. PMID- 1296417 TI - The rise of private practice: a growing disquiet with public services? AB - A survey of 325 national patients attending six private clinics in Port Moresby was carried out to determine the characteristics of those using private medical services. Most patients were employed in professional or clerical occupations. A sizeable proportion of private patients were from low and moderate income categories and over 40% of those interviewed said that they had to borrow the money to pay for the consultation. Education level was positively associated with both attending a private practitioner as first choice of treatment and enrollment in a medical insurance scheme. 15% of patients were medically insured, and they were more likely to choose a private practitioner as first treatment choice. The most common reason given for choosing private sector health care was that it was quicker, but a notable proportion, particularly amongst those who had previously attended government health services for the same complaint, thought that private clinics had better doctors or gave better medicine. The findings are discussed and contrasted with those from other developing countries. Conclusions are drawn regarding the significance of these findings both in relation to the upgrading of the public health services and the regulation and monitoring of private health services. PMID- 1296418 TI - Factors affecting the use of immunization among urban settlement dwellers in Papua New Guinea. AB - This paper examines the importance of selected social factors in the acceptance of childhood immunization in urban settlements in Port Moresby, Papua New Guinea. The study found that the provision of information to mothers on when to start immunization and how often the child should be immunized were key factors in determining immunization status. Maternal education was found to be positively associated with knowledge of immunization, but was not significantly associated with actual immunization practice. Over 70% of the women studied found out when to attend for immunization from the local maternal and child health (MCH) staff, hence emphasizing their importance in disseminating information. If coverage is to be increased further in urban settlements with mobile populations, maximal use must be made of local community organizations to disseminate the key immunization information and for follow-up of newborns and infants new to the community. Efforts to encourage mothers to deliver under supervision should also continue as this is an important point of first contact for immunization. PMID- 1296419 TI - Precipitation of asthma attacks in Melanesian adults by sodium metabisulphite. AB - Seven Melanesian asthmatic patients were challenged with substances that have been shown to precipitate asthma attacks in asthma patients in developed countries. Patients were challenged in a double-blind fashion using placebo and active substances. The active substances were tartrazine, sodium metabisulphite, aspirin and betel nut. All 7 patients were challenged with tartrazine and sodium metabisulphite; 5 were challenged with aspirin also, but only 2 were challenged with betel nut. Asthma attacks were precipitated by sodium metabisulphite in 3 patients. No other substances precipitated asthma. As sodium metabisulphite is a common food additive, these results suggest that processed foods introduced into developing countries may have an important role in precipitating asthma attacks in susceptible persons. PMID- 1296420 TI - The 'longlong' population of Ialibu District, Southern Highlands Province, Papua New Guinea: contact with health services and care in the village. AB - The aim of the study was to describe the general behaviour, living arrangements and level of health services contact of the mentally ill population of a health district in Papua New Guinea. The immediate relatives of 31 'longlong' people living in Ialibu District were interviewed. About half of the mentally ill subjects were able to cook and look after a garden. Just over half had engaged in physical violence or stolen and one-fifth had been physically restrained. Almost all were living in their own village although not all were living with their own families. Just over half had had contact with health services and this contact had usually been brief and, in the relatives' eyes, unsatisfactory. PMID- 1296421 TI - Determining drug dosages by height: applying a model made for coastal children in Papua New Guinea to children from the highlands. AB - A height scale for the determination of drug dosages in children of the Madang area was applied to children from the Nipa area of the Papua New Guinea highlands. In only 13 out of 1314 children (1.0%) did the use of the height scale result in drug doses below the recommended minimum dose per kilogram of bodyweight. The scale can therefore be used safely for highlands children in areas where facilities for accurate weighing are not available. PMID- 1296422 TI - Markers of hepatitis B infection in Tari District, Southern Highlands Province, Papua New Guinea. AB - Serum samples collected from two groups in the Tari District of Southern Highlands Province were assayed for markers of hepatitis B virus (HBV) infection. 85% of women of childbearing age were found to have markers of HBV infection; 37% were positive for HBV surface antigen (HBsAg), indicative of the chronic carrier state, and 6.6% were positive for HBV e antigen (HBeAg), indicating the presence of actively replicating virus. 75% of women negative for HBsAg were positive for antibody to HBV core antigen (HBcAb), a marker of past infection. A group of children aged 6 to 18 years showed a significantly lower prevalence of markers of infection (66%) but higher rates of HBsAg positivity (46%) and HBeAg positivity (30%). Only 37% of the HBsAg-negative children in this group were positive for HBcAb. The results from this serosurvey suggest that the major route of HBV transmission in this population is horizontal, between older children, though significant transmission also occurs during the neonatal period. PMID- 1296423 TI - Gentamicin resistance in fatal Klebsiella septicaemia. AB - The occurrence of antibiotic resistance in nosocomial infections is a common problem. This case details a fatality associated with Klebsiella infection acquired as a hospital inpatient. The transfer of gentamicin resistance between gram-negative bacteria could present a considerable problem in Papua New Guinean hospitals. PMID- 1296424 TI - Typhoid fever complicated by chloramphenicol toxicity, ataxia and psychosis. AB - A case of typhoid fever complicated by pancytopenia, cerebellar signs and psychosis is described. The association of reversible marrow suppression with chloramphenicol treatment and its clinical features are outlined. The features of cerebellar dysfunction and of psychosis in patients with typhoid are described. Recommendations are made to help identify the problem of chloramphenicol-induced marrow suppression when it occurs. PMID- 1296426 TI - Altitude sickness. PMID- 1296425 TI - Saint or sinner? A look at chloramphenicol. PMID- 1296427 TI - National nutrition survey. PMID- 1296428 TI - [Multiple positional relationships of nerves arising from the sacral plexus to the piriformis muscle in humans]. AB - The positional relationships between the piriformis muscle and the nerves which arise from the sacral nerve plexus were studied in 514 sides of 257 Japanese adults. These were classified into Types I-XIII and numerous subtypes based on: 1) the number of nerves perforating the piriformis muscle, 2) whether all or part of the nerve perforated the muscle, 3) the order of perforation and position in the muscle, and 4) communications between the nerves. In this paper, the multiple positional relations between the nerves and the piriformis muscle, the frequencies of the various types, and the order of priority concerning the perforation of nerves through the muscle are discussed. 1) The typical case, Type I, in which the piriformis muscle is not perforated by nerves except for a part of the superior gluteal nerve, was found in 309 (60%) of 514 sides. Types III-X, in which the muscle is perforated by additional nerves, were found in 195 sides (38%), and in 175 of these, all or part of the common peroneal nerve passed through the muscle. Types XI-XIII, in which the inferior gluteal nerve and other nerves pass above the piriformis muscle, were found in 10 sides (2%). Among all types, the following were generally seen: Type V, the piriformis muscle is perforated by both the inferior gluteal and common peroneal nerves; Type VII, the muscle is perforated by the two above-mentioned nerves and part of the posterior femoral cutaneous nerve (Fig. 16, Table 1). The common peroneal nerve followed two courses (a combination of over, through, and under the piriformis muscle) in 49 extremities. In the 4 cases of Type X (1%), the tibial nerve was divided into two components due to the intervention of the most caudal bundle of the piriformis or an unknown muscle. The dorsal component passed through the muscle, while the ventral component followed the typical course under the muscle (Figs. 9 11). Therefore, in the above-mentioned 53 cases as well as in other cases, the sacral nerve plexus cannot be divided into ventral and dorsal layers up to the sacral nerve roots, as in typical cases. Type II, in which the piriformis muscle is perforated by only a caudal branch of the superior gluteal nerve, was found in about 16% of 249 cases; this type was accompanied by some of the other types (Table 2). In the extraordinary case of Type XII with Type II, a branch of the superior gluteal nerve passed under the piriformis muscle (Fig. 13).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1296429 TI - [Study of the degree of pneumatization of the viscerocranium in man and pongidae]. AB - The volumes of the paranasal sinuses of 41 adult skulls of humans, gorillas, chimpanzees and orangutans, were examined with use of a Computertomograph type SOMATOM DR. The percentage distribution of the volumes of the different paranasal sinuses showed that the maxillary sinus always had the greatest volume. The maxillary sinus of the humans showed the smallest volume percentage in comparison with the pongids. The typical differences between humans and pongids were observed in the ethmoidal cells and the sphenoidal sinus. The ethmoidal cells of the gorilla and the orangutan have to be defined as rudimentary. Those of the humans come to more than 20% of the total volume of the paranasal sinuses of all hominoids. Differing from the humans, the sphenoidal sinus of the pongids pneumatizes almost the whole sphenoid bone. This volume percentage of the pongids is twice as high as that of the humans. In addition, an index was calculated from the volume of the facial skeleton volume and the total volume of the paranasal sinuses and defined as the degree of pneumatization. We found that the gorilla has the highest degree of pneumatization followed by the chimpanzee, the orangutan, and the humans. The lowest degree of pneumatization of the humans may be related to the reduction of the jaws. PMID- 1296430 TI - Variability of origin of serratus anterior muscle in Japanese. AB - The observations on 567 male and 251 female Japanese cadavers revealed that there was a wide variation of the lowermost origin of the serratus anterior muscle ranging from the 6th to the 12th rib. The most frequent cases in males were of the 8th rib type (42.5%), whereas those in females were of the 9th rib type (43.3%). There was a statistically significant difference in the distribution of the muscle origin between the sexes. The observations also showed that bilateral symmetry of the muscle origin was preponderant over asymmetry, the symmetric cases forming about seven-tenths of all individuals without sex distinction. PMID- 1296431 TI - Histogenesis of tunica media of the chick aorta. AB - We investigated the formation of the aortic tunica media in developing chicks from Hamburger-Hamilton stage (st) 12 to 1-day after hatching. At st 12, some cells of the lateral plate and the somite adjacent to the aorta extended processes toward the aortic endothelial tube. This is the first sign of the tunica media formation of the aorta. Then, these cells detached from the lateral plate and the somite attached to the aortic endothelial tube and covered it almost entirely by st 18. At this stage, bundles of microfilaments and spots of dense material were found in the peripheral region of cells of the tunica media (media cells); suggesting the earliest differentiation of smooth muscle cells. Subsequently, the tunica media increased in the number of cell-layers, reaching approximately 20 layers at st 34 (8-day incubation). The outer layers of the tunica media consisted of undifferentiated cells, whereas typical smooth muscle cells were found within the inner 4 to 5 layers. Elastic fibers first appeared at this st 34. With there was an increase in the elastic component, the tunica media assumed the lamella structure consisting of the alternating myocytes and elastic laminae. The aortic media 1-day after hatching essentially exhibited the same mature state as seen in the adult chickens. PMID- 1296432 TI - Defective response of plasma growth hormone to growth hormone releasing factor in growth hormone deficient children. AB - In an attempt to establish the reference pattern and the plasma growth hormone (GH) response to growth hormone releasing factor (GRF) (1-29)NH2, 5 normal stature with single kidney children and 14 with idiopathic GH deficient dwarfism received intravenous injections of 1 microgram/kg GRF(1-29)NH2. Plasma GH levels were measured at 0, 15, 30, 45, 60, 90, and 120 min after injection. The results showed that, first, in normal stature with single kidney children, each plasma GH reached peak level (80.31 +/- 19.28 ng/ml) at 45 min after injection. Second, the majority of those with GH deficient dwarfism also obtained maximal GH levels (13.10 +/- 10.78 ng/ml) at 45 min after injection but at significantly lower levels than the normal children (P < 0.01). To compare with that obtained after the insulin-induced hypoglycemia test, the peak GH level after GRF was higher but there was no significant correlation between them. The maximal GH level after GRF(1-29)NH2 injection did not show significant correlation with either chronological age or bone age. Third, 3 of 14 (21.4%) with GH deficient dwarfism had half response to GRF(1-29)NH2. It is reasonable to assume that out of these patients' GH deficiency is of hypothalamic origin. Therefore, GRF test is a safe and useful test for differential diagnosis of defect level in GH deficiency and may become a therapeutic regimen. PMID- 1296433 TI - Urinary N-acetyl-beta-glucosaminidase (NAG) in children receiving antiepileptic drugs. AB - The activity of urinary N-acetyl-beta-glucosaminidase (NAG) was measured in random urines using the ratio (NAG index) of NAG to grams of urine creatinine in 102 epileptic children taking antiepileptic drugs (AEDs). A high urinary NAG index (2 SD or more above the mean for the age-matched control/normal subjects) was detected in 40 (39%, 40/102) epileptic children with AEDs. None of the 40 epileptic children with abnormal urinary NAG excretion had significant proteinuria. Among the 83 epileptic children under monotherapy, 29 cases (35%) had elevated urinary NAG excretion. Valproic acid presented the highest incidence of abnormal urinary NAG index (78%, 7/9 cases) within the monotherapy group, and the incidence was statistically significantly higher than that (26%, 14/55) in the carbamazepine group (p < 0.005). In the monotherapy group, no significant difference in serum levels of AEDs was found between children with normal urinary NAG excretion and those with abnormal. Nineteen epileptic children were treated with more than one AEDs. Eleven of them (58%, 11/19 cases) had a high urinary NAG index. The incidence of high urinary NAG index in the polytherapy group and that in monotherapy group was not significantly different (p > 0.05). This study suggests that AEDs may be potentially nephrotoxic and that urinary NAG may play a role in screening renal tubular injury in epileptic children under therapy of AEDs. Further investigation should be conducted to determine whether the effect of AEDs on renal tubular cells is or is not reversible. PMID- 1296434 TI - Is IVP necessary in children with urinary tract infection? AB - A prospective study was conducted to determine the role of intravenous pyelography (IVP) in detecting the associated urinary tract anomalies in children with urinary tract infection (UTI). A total of 143 cases with confirmed UTI all received renal sonography (RS), voiding cystourethrography (VCUG) and IVP, to evaluate for G-U tract anomaly. Associated G-U tract anomalies were noted in 67 cases (46.85%). No single method was adequate in detecting all abnormalities. Based on the anomalies detected, we proposed and compared two different conditions in which IVP was required. In condition A, in which IVP was performed when abnormal finding were found in RS or VCUG, 67 of 143 cases with UTI (46.85%, 67/143) were required to have IVP, among them 32 cases yielded positive results and 35 cases negative results. Two cases of duplex collecting system (DCS) were found only on IVP would be completely undetected under this proposed condition. However, when IVP was recommended and performed at the time of high grade VUR in VCUG or any abnormality in RS (condition B), 43 of 143 patients (30%, 43/143) with UTI were required to undergo IVP, yielding abnormal findings in 30 cases (70%, 30/43) and normal findings in 13. This would leave four cases of DCS undetected, including the 2 detectable only by IVP plus 2 more that showed low grade VUR on VCUG. However, these 4 cases would not result in progressive renal damage in long-term follow up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296435 TI - [The coexistence of vesicoureteral reflux and ureteropelvic junction obstruction in children]. AB - From January 1982 to December 1990, there were 229 cases with 337 ureters having vesicoureteral reflux (VUR). Thirteen of them (3.86%) were also found to have ureteropelvic junction (UPJ) obstruction in the same ureter. They were categorized into three groups based on the therapeutic implications. Group 1 (two ureters) underwent pyeloplasty. Group 2 (two ureters) received both pyeloplasty and reimplantation. The remaining nine ureters having VUR and pseudo-obstruction fell into group 3, and two of them became true UPJ obstruction eventually. We stressed the importance of evaluating upper urinary tract in all refluxed ureters with inappropriately dilated renal pelvis. By doing that we can avoid unnecessary surgery and prevent complications from wrong sequence of operation to a least extent. PMID- 1296436 TI - [Educational effects of a short-term diabetes camp for children]. AB - A Diabetes camp provides children with fun and educational experience. Seventeen diabetic school children (12 boys and 5 girls) participated in a short-term diabetes camp from April 16 to 17, 1988. Their ages ranged from 8.5 to 13.2 years with an average of 11.3 +/- 1.5 (mean +/- SD) years. The duration of their diabetes varied from 0.05 to 5.3 years with an average of 2.7 +/- 3.3 years. The camp staff consisted of a pediatric endocrinologist, 3 nurses, 4 dietitians, 3 social workers, 4 assistant diabetes educators, and 2 counsellors who were specialized in music and recreational activities. The children's abilities in managing their diabetes were assessed by using a scoring system before and after the camping. Wilcoxon matched-pairs signed-rank tests with significance levels set at p < 0.05 (two-tailed) were conducted to determine whether there were any significant changes in the results from pre- and postcamp assessments. The children showed significant improvement in using glucose-monitoring devices, drawing insulin, injecting insulin, and choosing the right exchange of food with the p values of less than 0.05, 0.01, 0.01, and 0.01 respectively. We concluded that this short-term diabetes camp was educational for school children with diabetes. The campers improved their knowledge and skill in management of diabetes. PMID- 1296437 TI - Late infantile form metachromatic leukodystrophy: report of one case. AB - Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder with autosomal recessive inheritance, in which cerebroside sulphate (sulphatide) accumulates in the central and peripheral nervous systems due to a deficiency of arylsulphatase A. This article presents a 2-year-old boy who had occasional shortness of breath, horizontal nystagmus and unstable gait for 3 months prior to the entry. He was admitted to our hospital due to shortness of breath, frequent apnea, generalized hypotonia and conscious disturbance. The lumbar puncture, brain CT scan, serum amino acid analysis, urine organic acid assay and nerve conduction velocity of lower extremities all showed negative findings. The electron microscopic finding of muscle elicited lipid deposition. The auditory brainstem response showed bilateral impairment. The routine EEG revealed diffuse slow waves. The brain MRI showed widespread low signals over the white matter of bilateral frontal and parietotemporal areas of the cerebral hemispheres, as well as the white matter of the bilateral cerebellar hemispheres, and the brain stem in the T1-weighted image corresponding the high signals in T2-weighted image. The blood leukocyte lysosomal enzyme activity test revealed arylsulphatase A deficiency. Rapid progressive neurological deterioration was noted since admission. Unfortunately, the patient expired due to respiratory failure in the final. PMID- 1296438 TI - Essential myoclonus: report of four cases. AB - Four cases of essential myoclonus in childhood are reported. These include three males and one female, whose age-at-onset ranged from 2 months to 16 years. All manifested as involuntary movement of face, neck, or extremities without any known etiology. Only one case has a family history of myoclonus. They showed no other neurological abnormalities. The image or electrophysiological studies of nervous systems were within normal limits except that electromyogram (EMG) showed myoclonic discharge. All were treated by clonazepam with or without valproic acid. No significant effects were noted. PMID- 1296439 TI - The hypoglossia-hypodactylia syndrome: report of two cases. AB - Two cases of hypoglossia-hypodactylia syndrome are reported. This syndrome is characterized by reduction in the size of tongue, micrognathia and variable limb anomalies. In these present cases, both karyotypes revealed normal. The unrelated parents and siblings are normal. Drug exposure to the mother during pregnancy was negative. Since this syndrome is rare and no previous report in Taiwan. So we report these two cases and review the literature. PMID- 1296440 TI - Electrophysiologic study and surgical ablation of atrioventricular nodal reentrant tachycardia: report of one case. AB - A 12 years old boy with frequent episodes of palpitation was found, by the electrophysiologic study, to have an atrioventricular (AV) nodal tachycardia. Endocardial mapping during surgery revealed that the earliest retrograde atrial depolarization of the tachycardia occurred at the posterior part of Koch's triangle. Under normothermic cardiopulmonary bypass, perinodal dissection was performed above the tricuspid annulus at the coronary sinus region. The retrograde VA conduction disappeared. Post-surgery the antegrade conduction had a Mobitz type I block which had returned to normal after the fourth month follow up. PMID- 1296441 TI - Pyogenic sacroiliitis in children: report of three cases. AB - We report three children who were treated for pyogenic infection of the sacroiliac joint. The disease, usually present in late childhood or adolescence, is uncommon and difficult to assess so that the diagnosis is usually delayed. The three patients were two boys and one girl, aged 14, 15 and 12 years, respectively. A detailed history and physical examination are very important for establishment of the diagnosis. All the three cases presented with typical clinical triad of fever, limping gait and buttock pain. Pelvis compression maneuver, which directly stresses the sacroiliac joint, may aggravate the joint pain and suggest this diagnosis. On physical examination, this test is positive in all our cases. Nuclear scintigraphy is useful for localization of early lesions. For detecting abscess formation, magnetic resonance imaging was performed in two cases and computed tomography in one. In one of the patients, computed tomography failed to demonstrate an iliopsoas abscess formation, which was proved by magnetic resonance imaging later. Staphylococcus aureus was isolated from blood in all three patients. Prompt antibiotic therapy reduces complication and operation is rarely needed. With rapid and appropriate medical treatment, all our patients recovered without an sequelae. PMID- 1296442 TI - Study on the concentrations of cerebrospinal fluid immunoglobulin G and albumin in children. AB - Concentrations of immunoglobulin G (IgG) and albumin in cerebrospinal fluid (CSF) and serum were measured in 118 "normal" Chinese children from birth to 15 years old to obtain the reference values for the evaluation of the blood-brain barrier (BBB) function. The values of the CSF/serum IgG ratio, CSF/serum albumin ratio and IgG index (IgG ratio/albumin ratio) were then calculated for each subject. A relation was found between the content of IgG in CSF and serum depending on age. The gradual decrease of CSF IgG and IgG ratio during the first 6 months indicated a postnatal impediment of the diffusion of IgG from the blood to the CSF. In the meanwhile the CSF/serum albumin ratio continued to drop until the age of one year. The slower slope of the decrement of the latter ratio further demonstrated the differential permeability of the BBB in favor of the shift of small molecular protein. The change of the protein permeability within the first year of life shows a characteristic of the maturational process of the BBB. Nevertheless, IgG index has no age-dependent variation throughout the childhood period. It remains constant in the absence of inflammation within the central nervous system. PMID- 1296443 TI - Identification of sex chromosomal abnormalities by fluorescence in situ hybridization. AB - Chromosomes can be specifically stained in metaphase spreads and interphase nuclei by fluorescence in situ hybridization (FISH). Case 1 was a 20 year-old female patient who had chromosomal analysis six years ago because of primary amenorrhea and short stature. Three cell lines were identified: 45, X (20%); 46, X plus an unidentifiable fragment (50%) and 46, X plus an isodicentric X chromosome of short arm fusion (30%). Case 2 was a 6 year-old girl with the problems of clitoromegaly and growth retardation. By use of in situ hybridization with biotinylated X and Y centromere-specific alpha repetitive sequence probes, we were able to identify the marker chromosomes to be X and Y-chromosome originated, respectively. The use of FISH can facilitate clinical cytogenetic diagnosis, and allows fast screening of a large number of metaphases. This technique is applicable to the screening of other types of chromosomal mosaicism as well. PMID- 1296444 TI - Newborns of Chinese mother with systemic lupus erythematosus (SLE). AB - From January, 1979 to December, 1990, 105 pregnancies of the 87 mothers with systemic lupus erythematosus (SLE) were studied. There were 15 (14.29%) fetal losses. Among the 90 livebirths, 23 (25.5%) were moderately premature; and 1 (1.1%), was extremely premature. All but 2 (2.2%) had an Apgar score more than 7 at 1 minute. There was no neonatal death. Significantly lower birth body weights were noted compared with the matched control group (p = 0.0001). Birth body length and head circumference were not different. Only 1 of the 13 newborns who had been small for gestational age at birth had body weight and length less than the 3rd percentile during follow-up. Three (3.3%) newborns presented as congenital complete atrioventricular block (CCAVB). Their mothers were all positive for SSA (Ro) antibody. One of them obligatorily needed pacemaker implantation. ECG abnormalities including multiple ventricular premature contractions, wandering atrial pacemaker, sinus arrhythmia, and first degree A-V block were detected in another six newborns. Congenital cardiac defect with secundum type atrial septal defect was noted in two newborns (2.2%). Among the 59 mothers who had been tested for SSA antibody, 29 (49.1%) were positive. The incidence of complete A-V block was significantly higher in newborns of mothers with SSA antibody (p < 0.001). On the contrary, the frequency of fetal loss has higher in newborns of mothers without SSA antibody (p = 0.0043). PMID- 1296445 TI - An echocardiographic study on asymptomatic multiple interatrial septal defects in newborns. AB - In a prospective study on the integrity of the interatrial septum in the neonates, multiple interatrial septal defects or openings with shunting were discovered in nine neonates by means of the color flow mapping technique used in their first week of life among 130 Chinese neonates. Eight of the nine neonates had two openings each, and the remaining one had four openings. Thus a total of 20 openings were found in the 9 neonates. Openings located between the tip of the flap valve and the superior limbus of the foramen ovale were classified as "location A openings" (valve-like openings). Those located at the flap valve itself were classified as "location B openings" (fenestrations). Each of the 9 neonates had one opening at location A, eight of them had another opening at location B; one had three openings at location B. Six of the nine neonates were followed up at age of one month, three months and six months by means of color flow mapping, with a total of six openings at location A and eight openings at location B. Four out of the six openings of location A and seven out of the eight openings at location B closed spontaneously before the age of six months. In conclusion, seven percent (9/130) of these Chinese neonates have multiple interatrial openings. The openings tend to close spontaneously, regardless of their locations. PMID- 1296446 TI - Extracorporeal shock wave lithotripsy in children: experience with the multifunctional lithotripter MFL 5000. AB - Extracorporeal shock wave lithotripsy (ESWL) has been proved to be an effective method of treating upper urinary tract calculi. However, there is little experience with the use of this approach in pediatric urolithiasis, especially for lower urinary tract calculi. Nine children, aged 1-18 years, were treated here with urolithiasis in the renal pelvis, lower ureter and bladder, using Dornier MFL 5000. A polystyrene plate was used to protect small children from chest damage. Prone position was routinely used to treat lower ureteral and vesical calculi, thus avoiding bony pelvis blockage of shock wave energy. Excellent pulverization was achieved in eight cases; fragmentation in only one case, then required cystolithotripsy for bladder stone fragments three months after ESWL. No patient had melena. Neither hemoptysis nor gastrointestinal complications were seen. Extracorporeal shock wave lithotripsy is a safe and effective method of treating urinary tract calculi in children. PMID- 1296447 TI - Inward rectifier and delayed outward potassium currents in isolated guinea-pig ventricular myocytes: maturation and its role in repolarization. AB - In accord with previous reports, we have found that action potentials triggered from isolated mature (> 1 month) guinea-pig ventricular myocytes showed a longer duration than those from the neonate (< 1 day). A whole-cell voltage-clamp technique has been used to identify the postnatal changes of inward rectifier (Ikl) and delayed outward potassium currents (Ik), which may be related to the action potential transition. Our results have shown that the degree of maturation of the neonatal guinea-pig is much advanced, as compared to neonatal rabbits and rats. Slope conductance (1230 +/- 110 pS/pF, n = 10, for neonatal, and 1450 +/- 450 pS/pF, n = 10, for mature guinea-pig, p > 0.05) and the inward rectification occurring over a potential range from -50 to -10 mV were relatively similar between the neonatal and mature guinea-pig myocytes. But, the slope conductance of Ik was significantly greater in neonatal (702 +/- 80 pS/pF, n = 10) guinea-pig myocytes than in the mature (194 +/- 23 pS/pF, n = 10, p < 0.01). Therefore, we suggest that (1) the maturation of Ik appears later than that of Ikl, (2) age related decrease of the slope conductance of Ik could contribute to an age related lengthening of the action potential duration. PMID- 1296448 TI - Neonatal lupus erythematosus with negative anti-Ro and anti-La antibodies: report of one case. AB - Since 1981 when anti-Ro (SS-A) and/or anti-La (SS-B) antibodies were described to be present in infants with neonatal lupus erythematosus (NLE) and their mothers, subsequent studies have demonstrated the almost universal association of NLE with either or both of these autoantibodies. To our best knowledge, three cases of NLE were reported to be negative in anti-Ro (SS-A) and anti-La (SS-B) antibodies. We report one infant born to a mother with systemic lupus erythematosus (SLE). He had neonatal pancytopenia (thrombocytopenia, anemia, and leukopenia) which got resolved after intravenous immunoglobulin (IVIG) administration. Both anti-Ro (SS A) and anti-La (SS-B) antibodies were not detectable in his serum by immunodiffusion method while other such as RNP (nonspecific, including U1,U2,U3,...,U6), Sm and Scl-70 antibodies were all positive. This mother had all the above antibodies detectable in her serum. After excluding other possibilities, his pancytopenia was most likely to be attributed to neonatal lupus. We suggest that autoantibodies such as RNP and Sm antibodies may play an important role in the pathogenesis of thrombocytopenia of NLE. PMID- 1296449 TI - Rupture of chordae tendineae in acute rheumatic carditis: report of one case. AB - Acute rheumatic carditis is a rare cause of ruptured chordae tendineae of the mitral valve. Such rupture could result in severe mitral regurgitation and in fatality. Surgical valvuloplasty or valve replacement is usually necessary. A 12 year old boy presented with acute rheumatic carditis, complicated with rupture of the chordae tendineae of the mitral valve leading to intractable congestive heart failure and cardiogenic shock. He was successfully treated by a simple repair of the chordae and by mitral valvuloplasty. PMID- 1296450 TI - [Haemophilus influenzae cellulitis of the hand: report of one case]. AB - Cellulitis of extremities due to Haemophilus influenzae is rare in children. Only 60 cases of Haemophilus influenzae cellulitis of the extremities have been reported. It usually affects young children between the ages of six and 24 months. The lesion often presents with a red-to-bluish-purple discoloration overlying the involved area. High fever and leukocytosis are commonly found. Culture of needle aspirate and blood with appropriate media is necessary for diagnosis. Early diagnosis is especially important because of associated bacteremia and the subsequent possibility of life-threatening complications such as meningitis. We reported a 8-month-old female infant with Haemophilus influenzae type b cellulitis over the right hand. She was admitted due to high fever and painful swelling of the right hand. Edematous right hand with dusky erythematous skin over the dorsum and swelling of the palm with limitation of range of motion were noted on admission. Smear of needle aspirate revealed gram negative bacilli and beta-lactamase(-) Haemophilus influenzae type b was cultivated in the blood culture. She was successfully treated with ampicillin and discharged with stable condition. PMID- 1296451 TI - [Pancreatoblastoma: report of one case]. AB - Pancreatoblastoma is an extremely rare pancreatic tumor in childhood, comprising 0.5% of pancreatic non-endocrine tumors. It mostly affects children of under 8 years old without special sexual predilection. Abdominal mass is the dominant clinical feature and abdominal X-ray, sonography, UGI series, CT scan are of assistance in establishing diagnosis. The presence of acinar cells with zymogen granules, squamous metaplasia and endocrine components makes the diagnosis. We report a case of 4-year-old girl, who suffered from abdominal pain for two months. Abdominal mass was found at our OPD and abdominal sonography, UGI series, CT scan all indicated a parapancreatic tumor. AFP was 4700 ng/ml. Laparotomy confirmed a pancreatic tumor and only partial excision was performed due to tumor invasion and adhesion to major vessels. Diagnosis of pancreatoblastoma was made by pathohistology, cytochemical special stains and electronic microscopic examination of the tumor. Neither chemotherapy nor radiotherapy was performed due to family refusal. Then patient followed up at NTUH OPD regularly. Unfortunately patient expired because of the regrowth of residual tumor eight months later. PMID- 1296452 TI - Ubenimex (Bestatin), an aminopeptidase inhibitor, modulates protein kinase C in K562 cells. AB - Ubenimex (Bestatin) is a potent inhibitor of aminopeptidases (APase) including APase N (EC 3.4.11.2), a widely distributed membrane-bound metalloprotease. Binding of Ubenimex (UBX) to cells has been implicated in a variety of its biological activities, while little evidence has yet been provided as to any subsequent mechanisms of intracellular signal transduction. We now examined the possible involvement of protein kinase C (PKC), a key regulator in transmembrane signaling. Human leukemia K562 cells were cultured in the presence or absence of UBX (1 to 50 micrograms.ml-1, 1 to 72 h), and the subcellular distribution as well as phorbol-12, 13-dibutyrate (PDBu)-induced redistribution of PKC activities were assessed. The membrane-bound enzymatic activity tended to increase in the presence of UBX, while a significant loss of the activity was demonstrable upon subsequent exposure to PDBu (100 nM, 10 min) in both the cytosolic and membrane fractions. Specific binding of [3H]PDBu to intact K562 cells was also down modulated with UBX concentration- and time-dependently, suggesting loss of PKC enzyme protein on the cell surface. Western blot analysis of the total cell extracts disclosed no appreciable alteration in the amount of PKC protein. APase inhibition with UBX was observable independently of PKC modulation. The present findings were discussed with reference to the possible differential mechanisms of PKC-mediated regulation of cellular responses depending on cell types. PMID- 1296453 TI - Partial purification of a high molecular weight hepatocyte growth stimulating factor from normal calf serum. AB - A heparin-binding protein, acting as a potent hepatocyte growth stimulating factor (HGSF) was extracted and partially purified from normal calf serum. HGSF stimulated DNA synthesis and proliferation in primary cultures of adult Balb/c mouse hepatocytes and in two liver-derived epithelial cell lines (C6 and C2.8) plated at low cell density in serum-free medium in the absence of epidermal growth factor. HGSF was non-dialyzable in M(r) 50,000 cutoff membranes, and was purified after chromatofocusing on PBE94 resin, (NH4)2SO4 precipitation (80% salt concentration) of the active fractions eluted at pH 5.7, flow chromatography and elution through Sephacryl S300 HR and HA-Ultrogel columns. The hepatotrophic activity was eluted with a protein fraction that was concentrated approximately 40,000 fold over the starting material. The effect was half maximal at approximately 50 ng/ml on adult hepatocytes in primary culture, HGSF had a molecular weight of 90,000-110,000 by gel filtration, was unstable on heat treatment and was completely inhibited after trypsin digestion and after reduction with dithiothreitol. HGSF did not stimulate growth in Balb/c 3T3 fibroblasts. When injected into partially (40%) hepatectomized Balb/c mice, HGSF increased hepatic DNA synthesis 2 to 4-fold over the background stimulation, at 20 hours after the hepatectomy. PMID- 1296454 TI - Immunological effects of a single evening subcutaneous injection of low-dose interleukin-2 in association with the pineal hormone melatonin in advanced cancer patients. AB - Recent experiments have shown that a great variety of neurohormones can interact with IL-2 in the modulation of host antitumor immune response. On the basis of these data, a study was started to evaluate the effect of the pineal hormone melatonin (MLT) on IL-2-induced immune changes in cancer. The study included 30 advanced cancer patients. They were randomized to be treated with IL-2 at a dose of 3 million IU subcutaneously twice/daily (8.00 a.m. and 8.00 p.m.) for 6 days/week for 4 weeks, with IL-2 once/daily in the evening, with IL-2 once/daily plus MLT at 10 or at 50 mg/day. MLT was given orally at 8.00 p.m. Both IL-2 given twice daily and IL-2 given once daily and IL-2 given once daily in association with MTL induced a significant increase in mean number of lymphocytes, T lymphocytes, NK cells, CD25-positive cells and eosinophils, whereas the single administration of IL-2 alone was unable to determine a significant rise in the mean number of immune cells. Soluble IL-2 receptor and neopterin increase was significantly higher during IL-2 given twice/daily than during IL-2 plus MLT, while no difference was seen in TNF rise. This study would suggest that a single daily injection of low-dose IL-2 is able to efficiently activate the lymphocyte proliferation in cancer patients when it is given in association with the pineal hormone MLT. PMID- 1296455 TI - Molecular cloning of interferon-gamma inducible genes from a murine pre-B cell leukemia. AB - In the present study, a pre-B cell leukemia L1210-C7, representing a very early stage of the B lineage, was used to characterize the molecular mechanisms exploited by IFN-gamma to modulate B cell activity. A cDNA library was prepared with poly (A)+ RNA from cells stimulated with IFN-gamma and three cDNAs clones complementary to IFN-gamma inducible mRNAs were isolated by differential screening. Of these, the 9.5 cDNA hybridized to a 2.4 kb mRNA not homologous with previously cloned IFN-gamma inducible mRNAs. Furthermore, when compared with RNAs obtained from cells of different origins (fibroblasts and T cells) the 9.5 mRNA appeared to be increased only in cells belonging to the B lineage. Taken as a whole, these results demonstrate that in leukemic pre-B cells IFN-gamma induces the expression of a gene that could be employed as specific cell activation marker. PMID- 1296457 TI - [Orthodontic treatment for orthognathic surgery: indications, possibilities and limitations]. AB - The relation between the maxilla and the mandible can be so discordant that it cannot be corrected with orthodontic treatment only in adults, neither with orthodontic and jaw orthopedic in children. In these cases, only a combination of orthodontic treatment and orthognathic surgery can give the most satisfying results. A careful analysis of all patient records and an accurate planning of all the consecutive procedures should precede this treatment. Nowadays, computer aided systems can provide substantial help in analysis and planning. In this article, possibilities and limitations of the orthodontic part of these treatments are elaborated. PMID- 1296456 TI - Effects of granulocyte-macrophage colony stimulating factor on cortisol, growth hormone, prolactin and melatonin in cancer patients (short communication). AB - Several interleukins and interferons have been proven to induce endocrine effects. On the contrary, only few data are available about the possible hormonal activity of hemopoietic growth factors. This study was carried out to evaluate the endocrine influence of GM-CSF in humans. The study included nine head and neck cancer patients, evaluated in basal conditions and after an acute subcutaneous injection of GM-CSF at a dose of 3 mcg/kg b.w., by determining serum levels of cortisol, growth hormone (GH), prolactin (PRL) and melatonin. Both cortisol and GH significantly increased in response to GM-CSF, while PRL, and melatonin were not influenced. This preliminary study shows that hemopoietic growth factors, as well as interleukins, may also play endocrine effects in humans. PMID- 1296458 TI - [Importance of diagnosis in facial pain]. AB - The diagnosis and treatment of facial pain remains a great challenge for oral and maxillofacial surgeons. By taking an exact anamnesis--especially a pain anamnesis -and by starting specific examinations the patient can quickly be recommended to a qualified therapist. The pain syndromes are classified according to the IASP (International Association for the Study of Pain). The pain syndromes the maxillofacial surgeon is most frequently confronted with--idiopathic trigeminal neuralgia, atypical facial pain and the temporomandibular joint--are described. The necessity of a multidisciplinary examination is emphasized and the different diagnostic investigations are illustrated, particularly in the case of myo arthropathy. Beside the analysis of temporomandibular joint dysfunction, a radiologic examination is performed. In some cases the advise of a neurologist, ophthalmologist or otolaryngologist may be indicated. PMID- 1296459 TI - [Panoramic dental studies in systematic screening: useful or superfluous?]. AB - In the framework of a programme of systematic screening, a study of dental health of the population was completed on 791 members of the personnel of a service company together with their spouses. This multicenter study was completed in Belgium, by systematic panoramic dental radiography. Dental anomalies were found in 45.8% of the population studied. These 332 positive dental panoramic radiographies reveal on average 2.4 anomalies for each positive case. These anomalies are significantly (p < 0.05) more frequent among older age groups (51% among those over 45 years of age, 39% among those under 35 years). There is no important difference between the sexes, although a non-significant occurrence of anomalies can be observed among men over 45 compared to women of the same age. An active study of pathologies upon a "healthy" population by means of panoramic and clinical dental examination would therefore seem to be of interest. PMID- 1296460 TI - [Value of an anatomo-morphological classification of Class II]. PMID- 1296461 TI - Peripheral ameloblastoma: case report. AB - A case of peripheral ameloblastoma, a rare odontogenic tumour, is presented. This tumour appears to differ from endo-osseous ameloblastoma by the absence of local malignancy. It exhibits a less aggressive and destructive behavior and does not invade the underlying bone. Conservative treatment of the tumour is the treatment of choice. PMID- 1296462 TI - Comparison between specific IgE measured by RAST, two chemiluminescent assays and skin prick test. AB - Two hundred adult patients referred to a regional outpatient allergy clinic were skin prick tested and their specific IgE against ten inhalant allergens was measured by three different assays: the classical radioallergosorbent assay, Phadebas RAST (P-RAST), (Pharmacia AB, Uppsala, Sweden), the multi-allergosorbent chemiluminescent assay CLA (MAST), (Dome/Hollister-Stier, Miles Ltd., UK), and the immunocheminometric assay, MAGIC LITE SQ Specific IgE (ML), (ALK Laboratorierne, Horsholm, Denmark). Skin prick test (SPT) was performed with extracts from the same companies. Marked differences between the assays were seen especially in the low range. Specific IgE was detected in 17% of the samples by P RAST, in 66% by CLA, and in 17% by ML. Frequency distribution of P-RAST and ML measurements showed a peak at zero and a gradual decline towards larger values, whereas distribution for CLA was U-shaped with a peak at zero and another peak close to maximum reactions. Kendall's rank correlation coefficient being 0.80 for P-RAST vs. CLA. Correlation coefficient between measurements of specific IgE and SPT was high for CLA (0.65). Even in the low-level subgroup where IgE was detected by CLA only, a high correlation (0.60) between CLA and SPT was observed. In conclusion marked differences were observed between the three assays for specific IgE measurement. The CLA system seems to be more sensitive than the conventional P-RAST and ML, but further studies should reveal whether this extra sensitivity is clinically useful. PMID- 1296463 TI - Allergy to heparin. Special problems set by pregnant women. AB - Oral anti-coagulants are always contra-indicated for pregnant women. Only anti coagulants of the types of heparin or its derivatives may be used. However, some patients have an allergy to heparin. In this article the correct action to make both for diagnosis and prevention is studied. We present 2 observations of heparin-allergic pregnant women with, in the first case an attempted tolerization which failed and in the second case there was success in a second pregnancy with low-molecular weight heparin. PMID- 1296464 TI - Monitoring of various types of immunotherapy with gramineal pollens. I. Variation of clinical and biochemical parameters. AB - We assessed the clinical effectiveness and adverse effect of various types of immunotherapy on 42 pollinotic patients by monitoring their evolution on administration of Perennial lolium specific extract standardized in protein nitrogen units to 14 of them, the same extract but standardized in biological units (BUs) to another 13, and an extract containing four different pollens standardized in BUs to the remaining 15. For this purpose we measured clinical and medicinal scores, liver and kidney biochemical parameters, skin reactions and circulating immunocomplexes (CICs), both before immunotherapy was started (basal levels) and after 3, 6 and 12 month's treatment. We found no significant differences in clinical effectiveness or the occurrence of any adverse effects on administration of the different immunotherapies after one year's monitoring. We did found gradually decreased reactions to the skin tests, which thus provide a reliable means of monitoring allergen-specific immunotherapy. PMID- 1296465 TI - Monitoring of various types of immunotherapy with gramineal pollens. II. Variation of humoral immunochemical parameters. AB - We monitored the total and Perennial lolium-specific IgE, IgG, IgM and IgA serum levels of pollinotic patients under three different immunotherapeutic treatments with gramineal pollens over a one-year period. We found statistically significant (p < 0.05) decreases in the total serum IgE levels in successive controls performed after 3, 6 and 12 month's treatment with respect to the basal control levels. The specific IgE levels also decreased gradually throughout the study, while the total serum IgG and IgM levels increased significantly over the first 3 months, and those of IgG continued to increase up to the sixth month. Finally, the total serum IgA levels did not change significantly during the first year of treatment of our pollinotic patients. PMID- 1296466 TI - [An integrated approach to the psychological features of the asthmatic child]. AB - The work starts from the interrelation that occurs in asthmatic children between physical and psychical aspects. We carry out the experiment on an instructional programme as an efficient method of intervention that on one hand improves the levels of personal, social school and family adaptation and that on the other hand helps to modify the wrong attitudes about the illness, presuming that, in some way, it will be a relief in the physical aspect of the illness. The sample chosen by randomization and stratification from the Allergy Service of the Insular Hospital of Gran Canaria was tested using an experimental and control placebo with retest design. The children were between nine and eleven years old. The results for the adaptative aspects of the subjects were similar to the ones that Doctors Hernandez and Hernandez from La Laguna University (Canarias) got through similar studies, though the outcomes were not as successful as we hoped in cognitive/affective and social restriction. About the modification of the more internal aspects of asthmatic problems the programme was successful though we didn't modify some attitudes. We had the improvements that we hoped in some physical aspects as secondary effects but it seems that the programme can have more influence among them. PMID- 1296467 TI - Skin prick testing with standardized extracts from 3 different manufacturers. A comparative randomized study. AB - The aim of this study was to compare skin reactivity to routine allergen prick test with panels of allergens, supplied by three different manufacturers. The allergens comprised ten aero-allergens commonly used for skin prick test in Northern Europe, and included pollen, dander, house dust mites, and moulds. Two hundred consecutive patients were tested. The methods for standardization of allergen extracts, declaration of allergenic potency, and recommended lancets differed. The equipment were Soluprick SQ (Allergologisk Laboratorium A/S, Denmark) (ALK), Alphatest (Dome/Hollister-Stier, U.K.) (DHS), and Phazet (Pharmacia, Sweden) (PHA). The coefficient of variation for the allergen coated PHA (same lancet was applied twice) was 0.31, and for ALK and DHS allergen extracts 0.13 and 0.18, respectively. The frequencies of patients with positive reactions to the various allergens were generally similar, although DHS appeared to elicit less positive reactions to Timothy, dog, and Dermatophagoides pteronnyssinus. For the individual physician, it may be important to know the allergenic activity of the different allergens in his routine panel compared to the activity in other similar panels. PMID- 1296468 TI - Alveolar macrophages from AIDS patients spontaneously produce elevated levels of TNF-alpha in vitro. AB - In vitro production of TNF-alpha by alveolar macrophages was investigated in 15 AIDS patients with acute interstitial pneumonia and in 4 patients with asymptomatic HIV infection (anti-HIV+) and was compared to that observed in 6 patients with chronic pulmonary disease and in 5 normal controls (undergoing a fiberoptic bronchoscopy for suspected lung malignancy), all 11 HIV negative. Our results show that unstimulated alveolar macrophages of AIDS and anti-HIV+ patients released much more TNF-alpha than subjects with chronic obstructive pulmonary disease or healthy controls did: this overproduction may play a role in the pathogenesis of lung damage infection and particularly in AIDS patients. PMID- 1296469 TI - [Food allergy]. PMID- 1296471 TI - [New diseases born from clinical observation]. PMID- 1296470 TI - Innovation at the work site. Delivery of nurse-managed primary health care services. PMID- 1296472 TI - [Acquired atrophic pigmented band-like lesions following Blaschko's lines]. AB - Over a seventeen years period we observed 5 patients presenting with very similar lesions the equivalent of which we could not find in the literature. These were pigmented and more or less atrophic bands which exactly followed Blaschko's lines. The lesions appeared during childhood or adolescence, between the ages of 6 and 20 years and always were unilateral. In all cases they were located on the trunk where they formed a recumbent "S" pattern characteristic of Blaschko's lines. They often started 3 to 6 cm away from the posterior midline and ended precisely on the anterior midline. These bands varied in number and in 3 out of 5 cases they were associated with pigmented atrophic bands or lines on the limbs of the same side. The intensity of pigmentation and atrophy was variable. The lesions were asymptomatic and only caused a cosmetic prejudice. They were perfectly fixed, and during a 2 to 30 years observation period they remained unmodified. The five skin biopsies performed on 3 patients showed no abnormality of the epidermis other than irregular and moderate hyperpigmentation of its deep part. In the dermis, there was no distinct pigment incontinence, no inflammation and no alteration of connective tissue texture; the elastic network was invariably normal. The impression of skin atrophy was not due to true dermal hypoplasia and perhaps corresponded to atrophy of the subcutaneous cellular tissue. No biological disturbance was observed. These lesions can easily be distinguished from epidermic naevi, incontinentia pigmenti and areas of hypoplastic dermis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296474 TI - [Sevestre and Jacquet syphiloid erythema]. PMID- 1296473 TI - [Persistent photosensitivity: treatment with puvatherapy and prednisolone (corticopuvatherapy)]. AB - Eight patients, six men and two women, had chronic photosensitivity of 2.0 +/- 1.1 years' duration. The clinical and photobiological signs were consistent with a diagnosis of chronic actinic dermatitis syndrome. Photosensitivity was extremely severe, and the minimal erythematous dose (MED) in polychromatic light was dramatically decreased in all eight patients (82 +/- 20 mJ/cm2; range: 25-200 for a normal MED range of 1.000 to 2.000 mJ/cm2). Photopatchtests were positive to phenothiazine in four patients, to fragrance mix and oxybenzone in two patients, to balsam of Peru and musk ambrette in one patient each. Seven patients were treated with corticopuvatherapy. They all were markedly improved after one month of treatment, recovering normal MED and outdoor activities. Corticosteroid therapy was gradually reduced and stopped after 3 months, while puvatherapy was continued for several months. Treatment was withdrawn in three patients. The minimal erythematous dose was monitored after discontinuation of therapy: a progressive decrease of MED was observed, accompanied by a relapse in two of the three patients. This relapse was well controlled by another course of corticopuvatherapy. Four other patients had, after discontinuation of treatment, another course of corticopuvatherapy reinstituted in the early spring. Puvatherapy was stopped at the end of october. One patient did not receive corticopuvatherapy because she was living far from a puvatherapy centre. She was treated with azathioprine for 6 months without improvement, then with azathioprine+prednisolone 20 mg daily during 2 years with slight improvement. Corticopuvatherapy is a very efficient means of treating severe chronic actinic dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296475 TI - [Leg cellulitis caused by Aeromonas hydrophila. Medical treatment]. AB - A case of cellulitis of the leg caused by Aeromonas hydrophila in a cirrhotic patient is reported. The starting point of the infection could not be determined with certainty, but a direct local inoculation during foot-baths was suspected. Because of clinical signs suggestive of erysipelas, the disease was initially treated without success with penicillin G, which raises questions concerning the choice of the initial antibiotic therapy for cellulitis of the leg in immunocompromised patients, pending the bacteriological results. A purely medical treatment (adequate antibiotic therapy) resulted in complete cure of this patient, despite the fact that his lesions were necrotizing. PMID- 1296476 TI - [Lyell syndrome with ileal involvement]. PMID- 1296477 TI - [Prurigo pigmentosa]. PMID- 1296478 TI - [Eczema caused by contact allergy to tretinoin]. AB - Skin irritation induced by tretinoin is commonly observed, whereas allergic contact dermatitis to this drug is very rarely found in the literature. We report the case of a 34-year-old man who developed contact dermatitis in areas where a topical tretinoin preparation was applied. Patch tests were positive to tretinoin in low concentration and to isotretinoin. Oral administration of isotretinoin to this patient would carry a risk of systemic complications. PMID- 1296479 TI - [Association of lichen planus and thymus tumor]. PMID- 1296480 TI - [Medical secret in sexually transmitted diseases: cases of couples and adolescents]. PMID- 1296481 TI - [Botriomycosis and bacterial particles]. PMID- 1296482 TI - [Apropos of the article: Palmar punctate porokeratosis]. PMID- 1296483 TI - [A case for diagnosis: idiopathic calcinosis of the scrotum]. PMID- 1296484 TI - [Keratoacanthoma: therapeutic indications]. PMID- 1296485 TI - [Ofuji's disease and eosinophilic pustular folliculitis]. PMID- 1296486 TI - [Subacute cutaneous lupus erythematosus]. PMID- 1296487 TI - [Treatment of psoriasis in children]. PMID- 1296488 TI - [Balanced facial hydrophilicity of ioversol: a qualitative approach of hydrophilicity]. AB - Chimiotoxicity of iodinated contrast media is essentially due to non specific hydrophobic interactions with biologic proteins and membranes. These hydrophobic interactions depend both on the whole molecular lipophilicity and on the spatial accessibility of lipophilic molecular areas. Measurements of lipophilicity by partition coefficient, partially take into account the spatial localisation of hydrophilic groups around the lipophilic area due to the 1,3,5-triiodo-benzene. These measurements have to be completed by an accurate knowledge of the three dimensional localisation of hydrophilic groups to improve the biocompatibility of polyiodinated contrast media. The concept of evenly distributed facial hydrophilicity aims to minimize the accessibility to lipophilic area by a localisation of hydrophilic group on each plan of the benzene ring. The molecular structure of ioversol allows to put this concept in concrete form thanks to a tertiary anilide group which imposes on one hydroxy group to be located on each face of the 1,3,5-triiodo-benzene ring, providing facial hydrophilic protection. PMID- 1296489 TI - [Pharmacotoxicological profile of a non-ionic LOCM at high hydrophilicity: ioversol]. AB - The authors summarize the results of the main preclinical studies conducted to evaluate the tolerance of ioversol (Optiray), a new non ionic Low Osmolality Contrast Medium (LOCM). The various studies conducted by different routes of administration, in a number of animal species and at different dosages led to the conclusion that the product was equivalent or superior to the other non ionic agents used as references. This high inertia towards the biological systems particularly well evidenced in the neurologic tolerance studies has to be relied to the non ionic LOCM character of the agent but also to its highest hydrophilicity in its class and to the good distribution of this hydrophilicity around the molecule. These physiochemical characteristics which differentiate ioversol from the other products of its class make it a promising product for clinical use in humans. PMID- 1296490 TI - [Double-blind randomized study comparing ioversol 300 versus iopromide 300 abdominal computed tomography (CT scanner)]. AB - The authors compared ioversol 300 and iopromide 300 (ioversol 41 patients, iopromide 38 patients) in a randomized double blind study conducted on 79 patients undergoing abdominal computed tomography (CT) for a variety of indications. Each study was rated as diagnostic or non-diagnostic and the image quality was recorded. All side-effects were recorded. There was no significant difference in image quality and side-effects between both contrasts. In this study, both ioversol and iopromide provided excellent image quality and a low rate of side-effects. The authors conclude that ioversol is a safe and effective non ionic contrast agent for contrast enhanced body CT. PMID- 1296491 TI - [Ioversol 300 and iopamidol 300 in "whole body" computed tomography. A double blind clinical trial]. AB - The authors compared ioversol 300 to iopamidol 300 by double blind study in patients undergoing enhanced computed body tomography. There was no significant difference in clinical tolerance and efficacy between the two products. Only minor reactions were recorded in both groups. Contrast media were not considered to be responsible for the poor diagnostic quality of a few explorations. Ioversol 300 appears as a well tolerated and effective contrast medium for computed body tomography. PMID- 1296492 TI - [Evaluation of diagnostic efficacy and clinical tolerability of ioversol in "whole body" computed tomography in children. A non comparative phase III trial]. AB - An open-label noncomparative clinical study was conducted to evaluate the efficacy and tolerance of ioversol (Optiray 300), a new low-osmolality non ionic contrast medium, in body contrast-enhanced CT scanning in infants and children. Fourty pediatric patients who required contrast-enhanced CT scanning for evaluation of chest, abdominal or pelvic masses participated in the study. The vascular enhancement was judged to be excellent or good in 72.5% of the cases and the CT scans were judged to be diagnostic in 95% of the cases. Ioversol was well tolerated in the study with only two mild adverse reactions (nausea and vomiting, and metallic taste). PMID- 1296493 TI - [Clinical tolerability of ioversol 300 in brain computed tomography]. AB - Ioversol 300 (Optiray 300) is a new low-osmolality contrast medium. Optiray 300 was used in 92 patients for CT examination of the brain, to assess its clinical tolerance. Adverse reactions, when sensations of heat were neglected, were observed in 15% of the patients. All the adverse reactions, either observed by the radiologist or pointed out by the patient, have spontaneously disappeared without medical treatment and did not require hospitalization. Anaphylactoid phenomena were not observed. Optiray 300 appears as a well suited contrast medium for CT scan of the brain especially in patients with contrast medium high risk. PMID- 1296494 TI - [Evaluation of efficacy and tolerability of ioversol in intravenous urography. A comparative double-blind study versus iopamidol]. AB - The efficacy and safety of Optiray (ioversol), a new low osmolar non-ionic contrast agent were compared with Iopamiron in a double-blind randomized trial for intravenous pyelography. Concerning the diagnostic efficacy, Optiray 300 was equivalent to Iopamiron 370 for identical injection volumes. Significantly less reinjections were necessary with Optiray. Tolerability was found to be excellent, equivalent to the reference product. Optiray was found to be both well tolerated and of satisfactory diagnostic value. PMID- 1296495 TI - [Evaluation of clinical tolerability and diagnostic efficacy of ioversol 350 in UIV. A randomized double-blind study of ioversol 350 versus iohexol 350]. AB - The authors evaluated the clinical safety and the efficacy of ioversol compared to the reference contrast medium iohexol, during IVP. The clinical safety has been evaluated by the occurrence of side-effects. The efficacy was appreciated in terms of insufficient, medium, good or excellent. No side-effect was recorded for both contrast media. There was no difference in opacification quality and efficacy between ioversol and iohexol. The authors conclude that ioversol is a safe and effective contrast medium which can be, therefore, particularly recommended for urographic examinations of high risk patients. PMID- 1296496 TI - Ioversol in intravenous excretory urography. Evaluation of radiographic quality, patient tolerance and safety in four clinical studies. AB - Three randomized, parallel group, double-blind clinical trials (Study A, B and C) and one open-label, noncomparative clinical trial (Study D) were performed in adult patients to evaluate the radiographic quality, patient tolerance and safety of Optiray 300 (ioversol) in intravenous excretory urography. Comparative agents were iohexol (Study A and C) and iopamidol (Study B). Regarding the radiographic quality ioversol provided a statistically significant better ureter opacification (p = 0.029) compared to iohexol (Study A). In comparison to iopamidol (Study B) the mean degree of certainly with respect to the investigator's urogram-based diagnoses was statistically significant higher (p = 0.025) for ioversol. In these two studies the enhancement quality of regions visualized was higher in the ioversol groups than in the control groups. Regions investigated were: parenchyma, calyces, pelvis, ureters and the bladder. Ioversol, iohexol and iopamidol were found to be statistically comparable with regard to safety and patient tolerance. The results of these studies demonstrate that ioversol is an effective, well tolerated and safe contrast agent for intravenous excretory urography. PMID- 1296497 TI - [Evaluation of efficacy and tolerability of ioversol in intravenous urography]. AB - In an open clinical trial, 100 patients have been injected with ioversol (Optiray 350) during an IVP performed for various indications. This low osmolality contrast medium, which is remarkably hydrophilic, has exhibited a safety of use and image quality which were quite satisfactory. PMID- 1296498 TI - [Ioversol 300: clinical study in pediatric intravenous urography]. AB - The efficacy and safety of Optiray (Ioversol), a new low osmolar non ionic contrast agent, were evaluated in an open trial for pediatric intravenous urography. At a concentration of 30% iodine, Optiray had a good diagnostic efficacy and was found to be well tolerated. PMID- 1296500 TI - [Forum: reconstructive microsurgery of the mandible]. PMID- 1296499 TI - A double-blind comparative study on the contrast quality, tolerance and safety of ioversol 300 versus iohexol 300 in central venous angiography (C.V. DSA). AB - A prospective, randomised, double-blind study was performed to test the contrast quality, tolerance and safety of ioversol 300 mg/ml (Optiray 300, Mallinckrodt Medical, Inc., St-Louis, USA) versus iohexol 300 mg/ml (Omnipaque 300, Schering AG, Berlin). The study was conducted on 80 patients with peripheral vascular disease, who underwent central venous pelvis-leg angiography. The angiograms in the ioversol group were rated "very good" and "good" in 75.6% of the cases versus 51.3% in the iohexol group. Patient tolerance was nearly identical in both groups. On the 4 point rating scale for pain and heat sensations (1 = none; 4 = severe), the average heat scores were 1.28 for ioversol and 1.44 for iohexol. None of the patients complained of pain when receiving the injection. There were clinically significant changes of blood pressure in 3 patients out of each group and tachycardia in 5 patients in the ioversol group and 9 patients in the iohexol group. Seven out of 80 patients reported mild to moderate side-effects. These were related to the contrast medium in the case of 2 patients in both the ioversol and the iohexol group. All reactions resolved spontaneously or could be controlled by treatment. PMID- 1296501 TI - [History of microsurgical reconstruction of the mandible]. AB - The history of mandibular reconstruction, initially prosthetic, dates back to Ancient Egypt and China, but developed rapidly and diversified from the 19th century onwards when C. Martin, in 1889 developed his "immediate prosthesis applied to resection of the jaws", while A. Barth, in 1895, performed the first bone grafts. The more recent history of microsurgical reconstruction commenced with free rib transfers in 1977-1978 (Ariyan, Couly). Other microsurgical transfers, either pure bone or composite osteocutaneous, osteoseptal or osteomyocutaneous were then rapidly developed and used with varying degrees of success for mandibular reconstruction: inguinoiliac flap (Talyor and Watson, 1978), dorsopedal flap using the second metatarsal (O'Brien, 1979), forearm flap with the radius (Soutar and Mac Gregor, 1986), lateral brachial flap with humerus (Martin, 1988), free fibular flap (Hidalgo, 1989)... and the story continues. PMID- 1296502 TI - [Microsurgical reconstruction of the irradiated mandible with deep iliac circumflex flap]. AB - From 1979 to 1988, 30 osteomuscular or osteomyocutaneous free flaps of the iliac crest (revascularized by the deep circumflex pedicle) were used to reconstruct 28 mandibles severely compromised by radiotherapy exceeding 66 Grays. In addition to a perfect graft raising and microsurgical technique, perfect closure of the mucosal plane appears to be an essential factor of success. Over the years, this iliac crest flap appears to improve the radiological appearance of the bone stumps on either side. The procedure therefore appears to be particularly useful in the treatment of advanced radiation osteonecrosis. PMID- 1296503 TI - [Role of osteocutaneous external brachial flap in the treatment of composite loss of substance of the mandible]. AB - The authors report on their research begun in 1987 on this flap and its uses in reconstruction of composite defects of the horizontal and symphysical parts of the mandible, regardless of the cause of the loss. For treatment of average sized defects (less than 7 centimeters), it is reliable flap, easy to remove and to model by osteotomies, giving a thin skin mobile with bone and the removal of which results in only moderate development of scar tissue at the donor site. PMID- 1296504 TI - [Osteomuscular serrato-costal free flap: application to mandibular reconstruction]. AB - The serrato-costal free flap provides a large costal flap vascularized by a digitation of the serratus anterior muscle supplied by the dorsal thoracic artery. The flap is easy and rapid to raise with low morbidity. The repair obtained is functionally very satisfactory, but does not allow insertion of an implant. Six cases are reported. The indications of this technique of mandibular reconstruction are discussed. PMID- 1296505 TI - [Mandibular reconstruction by free transfer of the fibula after cancer excision]. AB - The authors present five cases of mandibular reconstruction using a vascularised fibula free transfer in cases of mandibulectomy for cancer. After giving a short account on the anatomy, they describe the technical details of fibula preparation and its transfer at the recipient site. The clinical observations are described. This recent technique seems to be developing, taking in account the qualities of the fibula: available bone length, possibility of performing osteotomies with preservation of the vascular supply, low morbidity at the level of the donor site, and satisfactory cosmetic and functional results. Despite of one recent failure, this short series seems to confirm the great interest in this type of bone reconstruction. PMID- 1296506 TI - [Free composite flaps with the fibula and their adaptation to mandibular reconstructive surgery. Apropos of 9 cases]. AB - Although revascularized fibula bone transfers have been used in reconstructive surgery of long bones for about fifteen years, the first reported cases of mandibular reconstruction were only published in 1989 by Hidalgo. The mandible and the fibula actually have very few points in common apart from their respective length and a certain similarity of cross-section. However, free composite flaps including the fibula are adapted to reconstruction of the mandible for several reasons: the length of the bone which can be raised (25 cm) and osteotomized into several fragments; the addition of other components (skin, aponeurosis, muscle, etc.) for skin and/or mucosal repair; the spatial independence of these various elements; the microsurgical qualities of the peroneal artery. This possibility of multidirectional and multiple tissue bony mandibular reconstruction is analysed on the basis of 9 clinical cases: 5 cases of traumatic sequelae of the lower third of the face following gunshot injuries, 2 cases of radiation osteonecrosis, 2 benign bone diseases. The triple bone, integument and vascular adaptation between the fibular donor site and the recipient site must be assessed preoperatively. Due to the quality of the morphological and functional results compared with the limitations of other free composite bone transplants, the authors propose free composite fibular flaps as adapted and adaptable solutions for one-stage reconstruction of extensive mandibular defects (> 10 cm) associated with small or large mucocutaneous lesions. PMID- 1296507 TI - [Should microsurgical mandibular reconstruction be dissociated?]. AB - Microsurgical transplant has the additional advantage over bone graft of being a composite tissue, resembling the defect it is intended to replace. This applies particularly to the mandible, as the mucocutaneous tissues are intimately applied over the bone. Regardless of the ingenuity of the transplant design and the different variations, none of the flaps used in this series of 37 microsurgical reconstructions was able to validly reconstruct bone and/or mucosa and/or skin in a single operative stage. It very rapidly became apparent that microsurgical reconstruction of the mandible needs to be divided into several stages in order to taken into account the mucosal defect. This choice of a more difficult alternative based on the lack of bone donor sites is compensated by the good tolerance of intestinal transfers to the buccal cavity. PMID- 1296508 TI - [mandibular reconstruction by free bone flaps with micro-anastomosis. Our current indications]. AB - The frequency with which difficulties were encountered in the reconstruction of the continuity of the mandible led us to attempt to systematize our indications. Although grafts, composite pedicle flaps and prosthetic guides still have their appropriate applications. Local conditions are more and more frequently amenable to free flaps. The factors guiding our choice are presented in detail: physical conditions, etiology and anatomy of the defect. In addition, the reason for choosing the type of free flap--iliac crest, fibula or external brachial--is discussed. PMID- 1296509 TI - [Practically: differential indications of mandibular reconstruction in maxillofacial cancerology]. AB - This study, based on the authors' experience, intends to determine the specific indications of mandibular reconstruction after oncological maxillofacial resections. Mandibular defects without osseous interruption do not necessarily need an osseous reconstruction: the esthetic and functional problems can be resolved using dental osseointegrated implants. On the contrary, mandibular defects with osseous interruption need imperatively an osseous and/or composite reconstruction: the best esthetic and functional results are obtained with an immediate reconstruction by an osseous or osteocutaneous free flap, either from the fibula or the iliac crest. The advantages and the disadvantages of all these reconstruction technics are detailed and largely illustrated. PMID- 1296510 TI - [No, Mozart was not trigonocephalic]. AB - The precise circumstances of Mozart's death and burial remain unclear at now. In this, the ownership of the skull supposedly belonging to the great musician and deposed at the Salzburg Museum is still a matter of controversy. A comparison between the cephalometric dental and cranial characteristics of this skull and portraits of Mozart, either genuine or reconstituted, has been established. The hypothesis of a trigonocephaly reported initially by Puech and Tichy seems to need modification to the benefit of a regional brachycephaly. On the other hand our study does confirm the great probability for this skull to be Mozart's one. PMID- 1296511 TI - [Diaphragmatic hernia complicating omentoplasty after thoracic wall excision. Reflections apropos of 2 cases]. AB - The authors relate two case-reports of diaphragmatic hernia occurring after antero-lateral chest-wall resection and repair with an omental flap. Both patients had undergone a prior lung resection for bronchogenic cancer, and the indication for chest-wall resection was parietal neoplastic recurrence. In both patients, the omental flap was brought up to the chest wall defect by a direct transdiaphragmatic route; prosthetic material was note used. The hernia presented once as early post-operative evisceration, and once as proximal obstruction due to gastric herniation. The causes of these two complications are analysed. Omentoplasty was justified twice, since the latissimus dorsi had been severed during the prior thoracotomy. Prosthetic material might have been useful to one of the patients, but not to the second who had undergone pneumonectomy. The transdiaphragmatic passage of the omentoplasty was certainly responsible for the herniae and should be avoided. PMID- 1296512 TI - [Musculocutaneoplasty by combined flap with tensor of the fascia lata- gluteus medius in trochanteric pressure sores. Apropos of a clinical case]. AB - The authors describe a musculocutaneous flap which can be used in trochanteric pressure sores in paraplegics. Described by Little and Lyons (1983), this reconstructive unit combines the proximal muscular segment of the tensor fasciae latae (TFL) and gluteus medius muscles in a round shaped flap pedicled on the lateral circumflex femoral artery. The anatomical basis of this muscle combination is found in the anastomotic network between the superior gluteal artery which supplies gluteus medius muscle and lateral circumflex femoral artery, the principal vascular pedicle of the TFL muscle. Cutaneous defects of the trochanter and associated osteitis are frequent complications in paraplegic patients which often require ostectomy and coverage of the bony prominence by well vascularised, padded skin. Musculocutaneous flaps are well suited for this purpose and we review various reconstructive units that may be brought into trochanteric defects. Among these, the gluteus medius-TFL flap appears to be an interesting option for, in case of recurrent ulcers, other donor areas are left intact, and the flap itself could give rise to a subsequent "traditional" TFL flap. PMID- 1296513 TI - [Surgical flaps with vascular pedicle in maxillofacial surgery in Cameroon]. PMID- 1296514 TI - Human reciprocal translocations: a new computer system for genetic counseling. AB - A new computer system for genetic counseling in reciprocal translocations is described. This system, namely RCPc (RCP counseling) is a knowledge base extracted from a data base called SCD (Structural Chromosome Data) which contains 1376 families carrying reciprocal translocations. RCPc gives key information for each translocation which allows an evaluation of the risk of unbalance at birth and a prediction of the characteristics of potential unbalances. This information could provide a useful basis for deciding whether a prenatal diagnosis is required and if so, the preferred sampling method i.e. amniocentesis or chorionic villus sampling (CVS). PMID- 1296515 TI - Population genetics of hereditary hemochromatosis in Saguenay Lac-Saint-Jean (Quebec, Canada). AB - Hereditary hemochromatosis (HH) is an autosomal recessive disorder that has a high prevalence in Caucasian populations. Based on HLA typing in 18 families, the gene frequency was estimated 0.12. The homozygote frequency was 0.014 and the heterozygote frequency was 0.21 in Saguenay Lac-Saint-Jean (SLSJ), a geographically isolated region of northeastern Quebec. The genealogical reconstruction showed that 15 of the 57 obligate carriers of the HH gene could be traced back to a unique ancestor in the 18th century. The mean coefficients of inbreeding and kinship were 17 and 15 times, respectively, higher in the HH group than in three control groups. The values of both coefficients were much higher than those found in other HH populations and in most of the other recessive disorders prevalent in SLSJ. PMID- 1296517 TI - Seckel syndrome: report of three sibships with the type I primordial dwarfism. Possible linkage with HLA locus. AB - The authors report on five cases of Seckel syndrome type I primordial dwarfism, belonging to three unrelated sibships. Immunological and cytogenetic investigations with DEB test did not evidence immunodeficiency or chromosomal fragility. HLA phenotype studies revealed an identical haplotype in affected sibs: a possible linkage with HLA is therefore suggested. Cranial magnetic resonance was performed in three patients and did not evidence any anomaly. One affected female showed precocious puberty at 7 years of age. PMID- 1296516 TI - Deletion 11q23-->qter (Jacobsen syndrome). Report of three new patients. AB - Three unrelated patients with de novo del 11q23-->qter are reported. Clinical features included growth and mental retardation, hypotonia, trigonocephaly, facial dysmorphism with hypertelorism, epicanthal folds, abnormally shaped palpebral fissures, eye globe malformations, depressed nasal bridge, "carp shaped" mouth, highly arched palate, low set and malformed ears. One patient had congenital heart defect, and reduced platelet count. This syndrome, originally reported by Jacobsen, is now corroborated by more than 35 patients and appears as the most common deletion involving 11q. Since deletion of subband 11q24.1 is critical for full expression of this syndrome, the JBS phenotype could be an example of contiguous gene syndrome. PMID- 1296518 TI - Trisomy of the short arm of chromosome 4: the changing phenotype with age. AB - In this paper the authors describe three patients with trisomy of the short arm of chromosome 4 with special attention to the striking phenotypic changes with age. When they get older the round face with chubby cheeks, deeply-set eyes and broad and flat nasal root with a bulbous nose tip becomes triangular or even long. Postnatal growth retardation is pronounced with short neck and broad, short chest with hyperkyphosis. The moderate to severe mental retardation is associated with almost absence of speech development, severe behavioural problems and poor fine motor development with persisting hypertonia, stiff, unstable gait, joint contractures and seizures. PMID- 1296519 TI - Is Yq11 the main critical segment in balanced Y;autosome translocations? AB - Balanced Y;Autosome translocations seem to be associated with male infertility whenever the Y breakpoint is located into Yq11 (where the azoospermia factor maps) or near its boundaries. By analogy with the effect on female carriers' fertility of balanced X;Autosome translocations, the band Yq11 emerges as the critical segment. This hypothesis implies that the subjacent mechanism is an impaired expression of the azoospermia factor--either through its physical disruption or via a position effect--rather than a disorder of the sex bivalent inactivation during prophase I. PMID- 1296520 TI - A 15p+ variant shown to be a t(Y;15) with fluorescence in situ hybridisation. AB - Prenatal diagnosis in two successive pregnancies revealed the karyotype 46,XX,15p+ (pat). Using the Y heterochromatic probe pHY3.4 and fluorescence in situ hybridisation, the variant 15 was identified as a t(Y;15)(q12;p11). Interphase scanning alone would have given a false result in both prenatal assessments and in the phenotypically normal father. PMID- 1296521 TI - Unbalanced karyotype due to adjacent 1 segregation of t(11;22)(q23.3;q13.2). AB - The 11q;22q translocations, whatever the breakpoints may be, are of particular interest because of their propensity to 3:1 segregation of the chromosomes at meiosis I. Until now, no unbalanced karyotype resulting from 2:2 adjacent segregation was published among offspring of 11q;22q translocation carriers. The authors report the case of an unbalanced karyotype due to adjacent 1 segregation of a maternal translocation (11;22)(q23.3;q13.2). The proband's karyotype was 46,XX,-22,+der(22)(11;22)(q23.3;q13.2)mat. This finding demonstrates that adjacent 1 segregation is possible in t(11;22) with breakpoints at 11q23 and 22q13, and can lead to birth of viable infants. PMID- 1296522 TI - 46,XX/46,XX,del(20)(pter-->p12.2) mosaicism limited to fibroblasts associated with MCA/MR and severe growth deficit. AB - In this report the authors describe an 8-year-old severely mentally retarded girl with facial features resembling the facial dysmorphism seen in patients with Alagille-Watson syndrome, severe growth retardation and a 46,XX/46,XX,del(20)(pter-->p12.2) mosaicism in fibroblasts. PMID- 1296523 TI - Y aneuploidy: a further case of a male patient with a 48,XYYY karyotype and literature review. AB - An adult male with three Y chromosomes is reported. The patient showed some clinical features similar to those of Klinefelter's syndrome. This case represents the 6th instance described in the literature of a 48,XYYY karyotype without recognizable mosaicism. The authors compare the clinical symptoms with those of the five previously reported cases. PMID- 1296524 TI - Interstitial deletion and ring chromosome derived from 19q. Proximal 19q trisomy phenotype. AB - A small supernumerary ring chromosome has been found in a boy with overweight, dysmorphic facies and mental retardation. His mother had an interstitial deletion of the long arm of chromosome 19 and the same ring chromosome. By means of fluorescence in situ hybridization the ring chromosome was shown to be derived from the deleted chromosome, after the occurrence of two breaks: one in the centromere region, the other in the q-arm of chromosome 19. PMID- 1296525 TI - Trisomy 21 mosaicism in two subjects from two generations. AB - In the course of a chromosome fragility investigation on the cancer prone hereditary disorder xeroderma pigmentosum, a low proportion of cells with a 47,XY,+21 karyotype was found in lymphocyte cultures of a patient not showing any Down syndrome symptom. The presence of trisomy 21 mosaicism was demonstrated also in peripheral blood of the healthy father and confirmed by "chromosome painting" that allowed a rapid detection of chromosomes 21 on metaphase cells and interphase nuclei. The trisomic cell line was not detected in fibroblast cultures. The analysis of chromosome 21 heteromorphism indicated that in both subjects the mosaic could result from either a diploid or an aneuploid zygote. Since in the trisomic cell line of the father and the son the extra chromosome 21 seems to be the same, a predisposition toward mitotic errors (non-disjunction or anaphase lagging) may be postulated, leading to the recurrent gain or loss of a specific chromosome 21. In order to test the hypothesis of an abnormal mitotic behaviour of the chromosome 21, we investigated the centromere separation index and the DNA restriction pattern in Southern blots probed with satellite DNA sequences specific for chromosome 21 centromere. Both the approaches did not reveal any peculiar feature that may account for the genetically determined proneness to mitotic error observed in the family. PMID- 1296526 TI - [Rationale for a cost-effective technologic regimen for microbiologic antibiotic synthesis. Statistical modelling]. PMID- 1296527 TI - [Assessment of the cost-effectiveness of the technological regimen for microbiologic antibiotic synthesis]. PMID- 1296528 TI - [Effect of inoculum parameters on the specificity of secondary synthesis in cultures producing novobiocin and mycoheptin]. AB - The impact of the vegetative inoculum parameters on specificity of the secondary synthesis in the cultures producing novobiocin and mycoheptin was studied. During the study the fermentation conditions were varied by using the vegetative inoculum differing in the respiration rate after its transfer to the fermentation medium. To show the decisive role of the inoculum parameters in regulation of the specificity of the secondary synthesis, the dynamics of accumulation of certain metabolites forming from glucose along with the main antibiotic and the activity of the key enzymes of the carbohydrate metabolism during the culture growth in the fermentation media were studied. It was found that the specificity of the secondary synthesis with respect to certain metabolites was defined by the intensity of carbohydrate metabolism, i. e. the ratio of the activity of enzymes of glycolysis and the pentosephosphate pathway. In this regard, the inoculum with the maximum respiration rate in an amount of 10 to 20 per cent promoted the highest productivity of the mycelium by the synthesis of novobiocin and mycoheptin while the rate of accumulation of fatty acids, carbohydrates and phenol compounds (for Streptomyces spheroides) and mycopentene (for Streptoverticillium mycoheptinicum) decreased. PMID- 1296529 TI - [Effect of rifampicin on the synthesis of antibodies to fraction I of vaccine EV]. AB - Multifactorial analysis was used to study the influence of rifampicin on the dynamics of synthesis of antibodies belonging to IgM and IgG classes in mice immunized by fraction I of the vaccinal strain EV. Equations and quadric surfaces describing individual dynamics of antibody formation within a wide range of antibiotic doses and time of antibody content determination were developed by the experimental data. It was shown that within the range of the doses corresponding to the therapeutic ones in man rifampicin stimulated antibody formation. It had an inhibitory effect on antibody genesis only when used in the doses many times higher than the therapeutic ones. PMID- 1296530 TI - [Detection of persistent resistance to antibacterial drugs in various strains of Francisella tularensis]. AB - Under natural conditions, the Francisella tularensis strains AE-261 and P-13864 capable of forming the persist type of resistance to antibacterial drugs and being the cause of the infection in laboratory animals not responding to monotherapy with antibiotics were detectable. The antibioticograms of strains AE 261 and P-13864 under the in vitro conditions did not differ from those of the other studied strains responding to the antibiotic therapy. The observed phenomenon could be associated with individual peculiarities of the strains and their phenotypic variation in the host. Combinations of aminoglycoside antibiotics (streptomycin, gentamicin and amikacin) with rifampicin were shown to be highly active in the treatment of general forms of the infection due to such strains. The combined therapy of tularemia was also considered promising because of its high efficacy when the treatment was started at late periods as well as because unlike the monotherapy with the aminoglycoside antibiotics it provided complete elimination of the pathogen from the host. PMID- 1296531 TI - [Protoplast fusion in Streptomyces fradiae strains producing neomycin and tylosin]. AB - Interspecies fusion of protoplasts of the Streptomyces fradiae strains producing neomycin (an aminoglycoside antibiotic) and tylosin (a macrolide antibiotic) was performed with a view to isolate strains producing novel antibiotics. Fusion of the protoplasts of the neomycin- and tylosin-producing strains labelled by the resistance to monomycin and lincomycin, respectively, caused no formation of stable strains producing antibiotics differing in chromatographic mobility from the antibiotics produced by the initial strains. In fusion of the protoplasts of the unlabelled strains, heat-inactivated protoplasts of the active line of one strain (donor) and native protoplasts of the inactive line of the other strain (recipient) were used. When the neomycin-producing culture was used as a recipient the fusion led to formation of strain 195-34 producing antibiotics of the benzo(a)anthraquinone group. One of these antibiotics, i.e. antibiotic 34-I, proved to be a novel biologically active substance. After regeneration of the protoplasts of the initial strains, no stable strains producing antibiotics differing from neomycin and tylosin were isolated. PMID- 1296532 TI - [Assessment of the sensitivity of Neisseria meningitidis strains to benzylpenicillin using the disc diffusion method]. AB - The sensitivity of 235 N. meningitidis strains to 5 antibiotics was estimated by the diameter of growth inhibition zones according to the criteria recommended by a Laboratory (Marseilles, France) collaborating with the WHO. All the strains proved to be sensitive to benzylpenicillin when disks containing 10 and 2 IU of the antibiotic were used. The strains were also shown to be sensitive to chloramphenicol and tetracycline. 95.7 and 7.7 per cent of the strains were sensitive to rifampicin and oleandomycin, respectively. When the strain sensitivity was assayed with the disks containing 10 and 2 IU of benzylpenicillin by the more severe criteria recommended by J. Saez-Nieto et al., significant changes were detected: meningococci with relative resistance to benzylpenicillin were detected in various regions of this country and the number of such strains was found to have a tendency to slightly increase. PMID- 1296533 TI - [Energy metabolism in Staphylococci containing plasmids of resistance to a number of antibiotics]. AB - Activity patterns of membrane-bound enzymes of an antibiotic sensitive strain of Staphylococcus aureus 8325-4 and its variants containing the plasmids of resistance to penicillin, tetracycline, erythromycin and chloramphenicol were studied. It was shown that acquiring of resistance to the above mentioned antibiotics influenced cellular energy metabolism. The resistant strains exhibited an increase in the specific activity of NADN, malate and succinate oxidases, intensification of the ATP-hydrolyzing activity, changes in the activity of definite dehydrogenases and a decrease in the specific content of cytochromes. No changes in the composition of respiration carriers were detected. PMID- 1296534 TI - [Effect of various adamantane compounds on the reproduction of Sindbis virus. Isolation and properties of a resistant strain]. AB - Rimantadine and its structural analogs, i. e. amide of 1-adamantane carboxylic acid (AACA) and 1-adamantane acetic acid amide, were shown to be able to inhibit reproduction of Sindbis virus in culture Vero cells. AACA had the maximum antiviral activity. Subcultures of the initial sensitive population of Sindbis virus in the presence of AACA led to formation of mutants resistant to AACA as well as to rimantadine, adamantane acetic acid amide and ammonium chloride. The Sindbis virus population was heterogenous in sensitivity to AACA, which was evident from isolation of separate clones with various levels of sensitivity to the above mentioned compounds from the population. It was found that reproduction of the AACA sensitive and resistant strains of Sindbis virus differed: the latent period of the resistant strain was 2 hours longer than that of the sensitive strain. The same effect was observed in the comparative study on synthesis of the virus-specific RNA. PMID- 1296535 TI - [Comparative effectiveness of various antibiotics in the treatment of patients with meningococcal meningitis]. AB - The results of treating 322 patients with various forms of meningococcal infection accepted to a hospital within a year are presented. The patients were divided into 3 groups by the character of etiotropic therapy. The patients of group I were treated with benzylpenicillin and those of group 2 were treated with levomycetin sodium succinate. Group 3 included the patients, the therapy of whom with the above two antibiotics failed and they were subjected to treatment with cefazolin, cefotaxime, amikacin and other broad spectrum antibiotics. Benzylpenicillin generally proved to be the drug of choice in the antibacterial therapy of meningococcal infection. In comparison to levomycetin (chloramphenicol) it provide more rapid clinical recovery of the patients and normalization of the indices of the cerebrospinal fluid. Only failure of benzylpenicillin therapy was considered as an indication to the broad-spectrum antibiotics to be in the complex treatment of the patients. As additional methods for estimating the efficacy of antibacterial therapy it was recommended to employ calculation of the integral indices of hemograms (the leukocyte index of intoxication and the hematologic index of intoxication). PMID- 1296536 TI - [Immunochemotherapy of infants in the first year of life with intestinal infections due to opportunistic gram-negative aerobic bacteria]. AB - The clinical and microbiological observations of 50 babies of the 1st year of age with intestinal infections due to opportunistic organisms were made. The babies were treated with antibacterial drugs and an immunoglobulin preparation. It was shown that the combined use of antibacterial and immunological preparations in the treatment of the babies with the intestinal infections caused by opportunistic organisms provided their earlier clinical recovery and lowered the unfavourable effect of the antibacterial drugs on the intestinal microflora. PMID- 1296537 TI - [Clinical aspects of the pharmacokinetics of unasyn (an ampicillin-sulbactam combination]. PMID- 1296538 TI - [Cefoperazone and other third-generation cephalosporins]. PMID- 1296540 TI - [Hypercholesterolemia and prevention of the cardiovascular diseases related to atherosclerosis. Responses to 10 current questions]. PMID- 1296539 TI - [Construction of hybrid plasmids containing genes for erythromycin biosynthesis and amplifying sequence AUD-Sr1 of Streptomyces rimosus]. PMID- 1296541 TI - [Blood cholesterol and mortality]. AB - Mortality rates vary with serum cholesterol levels: the causal nature of this relationship is studied by prospective studies (analysis of associations) and unifactorial primary prevention trials (experimentation to determine causality). In prospective studies all cause mortality is often increased at low and high cholesterol levels because of the inverse relationships of this factor with cardiovascular mortality (positive) and non-cardiovascular mortality (negative). Coronary death increases proportionally to serum cholesterol levels in all populations, including those with low cholesterol levels, in both sexes and at all ages. The relationship with cerebrovascular mortality seems to depend on the clinical feature: increased mortality rate due to cerebral haemorrhage in patients with low serum cholesterol and a positive correlation with cerebral thrombosis. Mortality due to cancers is generally negatively correlated to serum cholesterol levels with a significant increase in mortality in patients with a low serum cholesterol. This relationship often becomes less significant as the time between measurement and death increases. Mortality due to violent causes is not usually related to serum cholesterol. The multitude of possible causes of confusion makes any causal interpretation of data illusory. Experimentation by unifactorial primary prevention trials is essential for any etiological research but none of the trials performed to date was designed to analyse the effect of lowering serum cholesterol on global or coronary mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296542 TI - [Relations between HDL-cholesterol and cardiovascular diseases]. AB - Many retrospective and prospective epidemiological studies have demonstrated an inverse relationship between HDL-cholesterol and coronary risk. The predictive value of HDL-cholesterol is observed both in asymptomatic subjects and those with a primary vascular event. Several genetic abnormalities may be responsible for low HDL cholesterol (under 100 mg/dl or 0.26 mmol/l) or for a less severe hypoalphalipoproteinaemia. Despite some very low values, these rare causes of HDL deficiency are not all atherogenic and serve to emphasize the complexity of HDL metabolism. The protective role of HDL is explained by a number of mechanisms such as their role in the reverse transport from the peripheral tissues to the liver, their anti-oxidant effect and the increase in prostacyclin levels. The correction of isolated hypoalphalipoproteinaemia by drugs is controversial, but associated hyperlipidaemic states would be an indication to use drugs which increase the HDl-cholesterol the most. PMID- 1296543 TI - [Role of triglycerides in cardiovascular diseases]. AB - The role of triglycerides in cardiovascular disease is a controversial subject. Despite differences of opinion, present data allow a certain number of conclusions to be drawn. Hyperchylomicronemia is not associated with atherosclerosis, whereas type III hyperlipidemia is very atherogenic. These two abnormalities are, however, rare, and the majority of hypertriglyceridemias are, in practice, associated with increased very low density lipoproteins. Many epidemiological trials do not identify hypertriglyceridemia as an independent risk factor when the cholesterol and, in particular, the HDL cholesterol levels, are taken into consideration. Nevertheless, these results must be interpreted with caution as hypertriglyceridemia represents a very heterogeneous entity which is closely related to many factors which affect coronary risk (hypertension, insulin resistance, sedentarity, and even tobacco consumption). Therefore, hypertriglyceridemia and hypo-HDL-emia may be the result of the same primary abnormality; as the HDL-cholesterol level is more stable, it is the parameter which will be identified as a protective factor in epidemiological trials. The available data is insufficient to affirm that therapeutic lowering of triglycerides is accompanied by a reduced coronary risk because none of the large scale trials were designed to analyse this problem. Despite these epidemiological data, the measurement of serum triglyceride levels remains important in patients with hyperlipidemia. PMID- 1296544 TI - [Serum cholesterol and cancer. Is there a causal relationship?]. AB - Several studies have reported an inverse relationship between serum cholesterol levels and the risk of cancer, especially of the colon (Seven Countries, Framingham, Chicago studies, London Whitehall Study, Paris prospective study, New Zealand Maori, Honolulu Heart Study, Hypertension Detection and Follow-Up Program, ...). For example, in the Multiple Risk Factor Intervention Trial (361 662 men), the global mortality graph was J-shaped, higher at either side of the 4.6-5.1 mmol/l value of serum cholesterol. This increased mortality with lower serum cholesterol levels was due to increased numbers of death from cancer. However, when the relationship is studied with respect to the time elapsed between the cholesterol measurement and death from cancer, the relative risk of death in the lowest decile with respect to the average of the following deciles, decreases with the period between measurement of the serum cholesterol and time of death. The negative relationship between serum cholesterol and death by cancer, very significant for deaths occurring within the first 5 years, disappeared almost completely for deaths occurring after 5 years. Other trials designed mainly to examine cardiovascular risk, and concerning smaller numbers, have not demonstrated this inverse relationship between serum cholesterol and cancer. This negative relationship between serum cholesterol and cancer must be acknowledged. It is weak and concerns mainly colonic cancer, especially in men in the elderly age groups. Several explanations have been put forward: influence of the combination of factors, competition of risk of death by other causes, chance, alteration of normal biological function of the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296545 TI - [Is regression of atherosclerosis possible?]. AB - Experimental studies have shown the regression of atherosclerosis in animals given a cholesterol-rich diet and then given a normal diet or hypolipidemic therapy. Despite favourable results of clinical trials of primary prevention modifying the lipid profile, the concept of atherosclerosis regression in man remains very controversial. The methodological approach is difficult: this is based on angiographic data and requires strict standardisation of angiographic views and reliable quantitative techniques of analysis which are available with image processing. Several methodologically acceptable clinical coronary studies have shown not only stabilisation but also regression of atherosclerotic lesions with reductions of about 25% in total cholesterol levels and of about 40% in LDL cholesterol levels. These reductions were obtained either by drugs as in CLAS (Cholesterol Lowering Atherosclerosis Study), FATS (Familial Atherosclerosis Treatment Study) and SCOR (Specialized Center of Research Intervention Trial), by profound modifications in dietary habits as in the Lifestyle Heart Trial, or by surgery (ileo-caecal bypass) as in POSCH (Program On the Surgical Control of the Hyperlipidemias). On the other hand, trials with non-lipid lowering drugs such as the calcium antagonists (INTACT, MHIS) have not shown significant regression of existing atherosclerotic lesions but only a decrease on the number of new lesions. The clinical benefits of these regression studies are difficult to demonstrate given the limited period of observation, relatively small population numbers and the fact that in some cases the subjects were asymptomatic. The decrease in the number of cardiovascular events therefore seems relatively modest and concerns essentially subjects who were symptomatic initially. The clinical repercussion of studies of prevention involving a single lipid factor is probably partially due to the reduction in progression and anatomical regression of the atherosclerotic plaque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296546 TI - [Optimal serum cholesterol and efficacy of methods for lowering cholesterolemia]. AB - Analysis of epidemiological studies enables definition of the optimal serum cholesterol level between 2 and 2.2 g/l (5.2 and 5.7 mmol/l). Higher levels are associated with an exponential risk of coronary artery disease: lower levels should be interpreted with caution because of the J-shaped curve of global mortality reported in several trials. In primary prevention, therapeutic trials have clearly shown that a significant reduction in the number of coronary event may be obtained by lowering the serum cholesterol (15 for every 1,000 patients treated). In trials performed to date this benefit has not resulted in any gain in global mortality. In secondary prevention, the benefits of lowering serum cholesterol on the incidence of coronary disease seems identical in terms of relative risk to that observed in primary prevention. Nevertheless, the benefits in terms of absolute risk are much higher because of the high incidence of coronary mortality in a patient population with a previous coronary event. Thus, for 1,000 patients treated, there are 50 less cardiac events and this is reflected in a reduction of global mortality of about 20 for every 1,000 patients treated. PMID- 1296547 TI - [Should men aged 20 to 30 years with hypercholesterolemia be managed in the same way as older men?]. AB - Serum cholesterol intervention studies have been mainly performed in middle-aged men. Is the extrapolation of these results to men aged 20 to 30 years justified? Atherosclerosis is a process which continues throughout life. It is clear that increased serum cholesterol levels are associated with a higher coronary risk. In addition, serum cholesterol levels increase with age up to 60 years old. Do young men obtain the same benefits from medical intervention as older men? Therapeutic trials have been performed in middle-aged men. The increase in life expectancy associated with a 6.7% lowering of the serum cholesterol by life-long dietary restrictions would only be 4 months in 20 year old subjects at high risk (hypertension, smokers, low HDL cholesterol). With a 20% reduction in serum cholesterol, the gain would be 12 months. There is no reason for not extrapolating acquired data in the over 30s to 20 to 30 year old subjects. Due to the fact that young subjects are exposed to the risk for longer periods, it is advisable to treat their hypercholesterolaemia even more seriously than that of older patients. PMID- 1296548 TI - [Should hypercholesterolemic women be treated?]. AB - There have been few studies designed to evaluate the problem of hypercholesterolaemia in women despite the fact that, like men, cardiovascular disease is their main cause of death. Serum cholesterol is a risk factor in women, but the increased risk appears at much higher values of serum cholesterol than observed in men. In women, low HDL-cholesterol seems to be the best predictive factor for the occurrence of a coronary event, especially if the triglycerides are raised. The absence of therapeutic data on the treatment of hypercholesterolaemia in women underlines the need for a specific trial to assess the effects of lipid-lowering drugs in this population. The cardiovascular benefits of hormone substitute therapy at the menopause have been reported in several studies and a large scale randomised trial is under way to confirm these results. The benefit of hypercholesterolaemic therapy in women with mild hypercholesterolaemia has not been proved. When the serum cholesterol level is over 3 g/l (7.77 mmol/l), early treatment is advisable. PMID- 1296549 TI - [Hyperlipidemia in patients over 60 years old]. AB - The management of hyperlipidemia in individuals aged 60 or over is a serious problem, given the frequency of metabolic abnormalities in this age group. The decision to treat must take into account a number of uncertainties. Hypercholesterolemia is a risk factor in the elderly and, in general, its importance varies like the other major risk factors (hypertension and smoking): the relative risk decreases with age but this decrease in relative risk is associated with an increase in the absolute risk because the prevalence of cardiovascular disease greatly increases with age. The serum cholesterol level increases with age but the physiopathological mechanism os this increase is poorly understood (reduction in the number of LDC receptors?). In the over 70s, serum cholesterol levels decrease, probably because of a selection due to the deaths of subjects at higher risk. No therapeutic trials have been performed to evaluate the effects of lowering the serum cholesterol in the over 60s. In addition, strict application of international recommendations in this age group would result in a large number of therapeutic interventions, the value of which would be questionable. Under these conditions, practical clinical advice is based on reasoned extrapolation of epidemiological data obtained in middle-aged men. Treatment should therefore be reserved for sever forms of hyperlipidemia, taking into consideration the life expectancy of the individual. PMID- 1296550 TI - [The facts about cholesterol (condensed translation and comments of the common declaration of AHA and NHLBI)]. AB - Many epidemiological and experimental studies have confirmed the continuous positive relationship between serum cholesterol levels and coronary risk. Therapeutic trials have demonstrated that the lowering of serum cholesterol by diet or drugs can lower this coronary risk. The benefits have been shown in men and women, the young and old, in those with a high coronary risk due to raised serum cholesterol and LDL and those with only moderately increased risk. In addition, therapeutic interventions on serum cholesterol are cost-effective. These observations more than justify the present national program of lowering the serum cholesterol. PMID- 1296551 TI - [Comparison of methods for determining the prececal nutrient digestibility and amino acid absorption of swine with ileorectal anastomoses and ileocecal bridge cannulas]. AB - The apparent precaecal nutrient digestibility and amino acid (a.a.) absorption of 10 diets were estimated in pigs with end-to-side ileorectal anastomoses (IRA) as well as with ileocaecal re-entrant cannulae (IZB). The digestibilities of organic matter and crude carbohydrates were significantly higher in IRA pigs than in IZB pigs in two resp. three diets only. There were no practical important differences for the digestibilities of crude protein and crude fat in all diets. Out of the 180 a.a. absorption comparisons only 20 (i.e. 11%) showed differences larger than 5%-units. The absorption rates of several a.a. were lower in IRA than in IZB pigs and of some other a.a. on the contrary. The methionine absorption of five legume diets and one barley + lysine diet were up to 15% resp. 4%-units lower in IRA pigs. Possibly this was due to the activity of microbes in the rectum in connection with a small intake level of protein bound methionine. In order to minimize such a falsification it is proposed to use the end-to-end anastomosis. The deviations in the apparent a.a. absorption between IRA and IZB pigs can be explained partly by differences in the quantity of precaecally excreted endogenous a.a. per 100 g DM intake. PMID- 1296552 TI - [The use of the mobile bag technique in swine. Determination of the apparent crude protein digestibility and amino acid absorption of feed and rations]. AB - The mobile bag technique (MBT) was used in two ileorectostomized and two intact pigs with duodenal cannulae, in order to estimate the precaecal and total crude protein digestibility and amino acid (lysine, methionine, cystine, threonine, tryptophan) absorption of ten single feedstuffs (field bean, lupin, rapeseed meal, fish meal, barley, wheat) and three diets. For each feed 36 bags were applied per animal. After a peptic predigestion in vitro, application of the bags through the duodenal cannula into the intestine and their passage through the gut, the residues remaining in the bags were pooled to collective samples and just as the original feed material analysed on dry matter, nitrogen and amino acids. The directly determined MBT-digestibilities (BV) and the values obtained by regressive calculations (BVb) have been compared with apparent digestibilities (sV) conducted from conventional digestion experiments. 74 per cent of all BV data was higher than the corresponding sV values. Similarities of BV with sV showed in 58 per cent, those of BVb with sV only in 17 per cent. In all cases differences of > +/- 4 digestibility units showed. Checking additivity of diet-BV by means of calculations from the BV of their single ingredients did not generally lead to the same results as the directly estimated diet-BV; in some cases the results were contrary. Therefore the use of MBT for mixed feed diets has to be further investigated. For single feedstuffs the MBT can be used successfully as a rapid and simple technique when regressive calculations are employed. PMID- 1296553 TI - [The use of the mobile bag technique in swine. 2. Determination of the apparent and true crude protein digestibility of 15N-labeled feed]. AB - In a series of experiments in two ileo-rectostomized pigs the precaecal apparent and true digestibilities for crude protein of seven 15N-labelled feedstuffs were studied using the mobile bag technique. True digestibility values of crude protein calculated with the help of isotope dilution were 4-14 units higher than the corresponding apparent digestibility values. This is caused by the infiltration of the bag residues with endogenous unlabelled nitrogen. In dependence on the kind of feedstuff the endogenous N portion in the bags amounted to 25-70% of the total N. In addition, the contamination is influenced by differences between the animals (mean 4-7%) and by different treatments of bags after gut passage (3-10%). PMID- 1296554 TI - [The energy metabolism of growing swine in a live weight range of 10-50 kg. 3. Energy maintenance requirement of growing swine]. AB - Investigations into the energy maintenance requirement yielded the following results: For the energy maintenance requirement (EMR) in dependence on live weight (LW) using the relation EMR = aLWb from 13 experiments, an exponent of the live weight of 0.647 +/- 0.054 (0.57 to 0.73) was found out. Increasing the protein content in the feed from approximately 17 to approximately 45% in 6 experiments lowered the energy maintenance requirements about 14, 4, 6, 2, 6 and 12% respectively. The animals' development had no influence on the difference. The amount of the energy maintenance requirement varied greatly between the experiments. Exclusively in the experiments with barrows, a lowest value of 634 and a highest value of 931 kJ metabolizable energy per kg LW0.62.d was measured. On average of 19 comparisons the energy maintenance requirement derived from growth and maintenance periods by means of regression analysis was significant (alpha = 0.05), about 4% higher than the energy maintenance requirement measured on maintenance level directly. PMID- 1296555 TI - [The energetic utilization of rations with molasses, dried sugar beets, apple pectin and lucerne leaves by adult swine]. AB - The energetic utilization of 6 rations with molasses, dried sugar beets, apple pectin and lucerne leaves was measured in 8 adult pigs by means of the respiration test technique. The energy digestibility of the rations ranged from 74 to 88%, the partial utilization of the metabolizable energy from 66 to 78%. From the results with apple pectin a mean energy deposition value of 7.2 +/- 12.5 kJ/g digestible pectin was derived. Taking into consideration results from previous recorded experiments and the high standard deviation for estimation of the energetic feed value as deposition effect of digestible pectin, 5 kJ/g are proposed. PMID- 1296557 TI - Sunflower meal as a major vegetable protein source in layers' ration. AB - An experiment was conducted with Starcross layers to evaluate the replacement value of sunflower meal (SFM) for cotton seed meal (CSM) and sesame meal (SM). The birds (aged 24 weeks) were given 4 isonitrogenous and isocaloric rations containing 0, 5, 10 and 15% dehulled sunflower meal. The substitution of SFM for CSM and SM did not generally affect the egg production, feed consumption, feed conversion nor did it have any effect on the quality of eggs as measured by Haugh Units (HU) and yolk index. Egg shell thickness, however, improved by increasing dietary levels of SFM. The feed costs per hen were generally lower for the SFM group since SFM was cheaper than CSM and SM. PMID- 1296556 TI - Preliminary investigation on the effect of dietary supplemental biotin and palm kernel oil on blood, liver and kidney lipids in chicks. AB - A total of 480 day-old broiler chicks were used in two trials conducted to investigate the performance and lipid contents of blood, liver and kidneys of birds when fed varying levels of palm kernel oil (0% and 2%) and biotin (40, 80, 120, 160, 200 and 240 mcg/kg feed) in a 2 x 6 factorial experimental design. The results showed that blood, liver and kidney lipid concentrations were significantly affected by dietary biotin treatments. While total lipid, free fatty acid, triglyceride and cholesterol contents were negatively correlated with dietary biotin level, phospholipid concentrations were positively correlated. Biotin-deficient chicks had significantly higher total lipid, free fatty acid, triglyceride and cholesterol but lower phospholipid contents in their blood and the two organs. Supplementation of the diet with 2% palm kernel oil significantly elevated blood phospholipid concentration, but depressed the accumulation of the other lipid fractions in both organs and the blood of birds. Blood, liver and kidney cholesterol concentrations were not affected by 2% fat supplementation. Observation on the lipid parameters coupled with the results on feed utilisation appeared to suggest that a minimum of 120 mcg of the vitamin per kilogram of diet was required by broiler chicks for optimum performance. PMID- 1296558 TI - [Concentrations of metabolites and hormones in the blood plasma of lactating dairy cows during treatment with recombinant bovine somatotropin (BST)]. AB - Sixteen lactating dairy cows were submitted to six injections in a four-week interval of either 640 mg prolonged release bST or of 640 mg saline (control, n = 8). The bST-treated animals were pair fed to the control cows, which were fed according to requirements. Fourteen days after each injection, blood samples were derived and analysed for metabolites and hormones. Plasma contents averaged 0.16 mmol/l non esterified fatty acids (NEFA), 2.69 mmol/l glucose, 0.43 mmol/l beta hydroxybutyrate, 0.024 mmol/l acetoacetate, 78.8 g/l protein, 4.6 mmol/l urea, 0.81 micrograms/l insulin, 44.4 ng/l thyroxine (T4) and 1.41 ng/l triiodothyronine (T3). The bST-application was without effect on the analysed plasma contents. PMID- 1296559 TI - [The nitrogen metabolism in the large intestine of ruminants. 8. Metabolism of intracecally infused 15N-urea with a supplement of pectin in heifers]. AB - Three heifers with live weights of 255, 261 and 300 kg were supplied with ileo caecal re-entrant cannulas, jugular vena catheters and bladder catheters. The ration consisted of 4 kg maize silage and 4 kg wheat straw pellets. In a previous period 50% of the digesta flow was collected over 12 h/d on 5 consecutive days and stored in a deep-freeze. During the main period the re-entrant cannulas were disrupted and the flowing digesta was quantitatively collected. Precollected digesta and pectin were infused into the distal part of cannula hourly for about 30 hours. During the first 24 hours the digesta was also supplemented with 15N labelled urea. The amount of pectin corresponded to about 10% of digesta dry mater. An analysis of urine, faeces, digesta and blood plasma were carried out. The application of pectin increased the 15N-incorporation in the bacterial protein of faeces from 4.7% (without supplementation in an earlier experiment) to 10.5% of the introduced 15N. The ammonia-fraction of faeces was markedly higher than the bacterial fraction. The 15N-utilization of urea by the microbes of large intestine was lower in the actual trial evident than with supplementation of starch in the anterior experiment. During the pectin administration the amount of urine increased in comparison with earlier experiments and according to the literature to about the 4.5 fold. The amount of passage of 15N at the ileum cannula (recycled 15N) was 3.8% of the 15N intake. It is the same amount as in experiments in which starch was applied. PMID- 1296560 TI - [The measuring frequency necessary for food intake and milk yield data in feeding studies in dairy cows]. AB - An individual feeding experiment was carried out which comprised the daily milk analysis from Monday to Friday with proportional samples from the evening and morning milkings and the daily intake of the individual feed components being ascertained. For various measuring frequencies the following calculations were made: the mean values and their standard deviations, the absolute and relative control errors and their standard deviations, the standard deviations for the measuring error and the simple linear correlations and regressions between the various measuring frequencies for the individual parameters. From the results one can conclude that, in individual feeding experiments with dairy cows, five milk analyses per week do not bring about an essential improvement of accuracy in comparison with two analyses. If the composition of the ration remains the same and the same roughage is offered ad libitum, one can project the measuring of feed intake on five days per week for that of the whole week. PMID- 1296561 TI - Effect of feed intake and dietary vitamin A levels on sheep performance. AB - A study was conducted on 20 "Rahmani" male lambs of 16 kg body weight fed on normal feed level and high vitamin A level (NF-HV); normal feed level and normal vitamin A level (NF-NV); low feed level and high vitamin A level (LF-HV) or low feed level and normal vitamin A level (LF-NV) till slaughter weight of 35-40 kg. Average daily gains of lambs were 211, 148, 117 and 87 g for the NF-HV, NF-NV, LF HV and LF-NV groups, respectively. The corresponding feed conversions were 4.3, 5.9, 5.0 and 6.4 kg DM/kg gain. Raising feed intake and vitamin A level enhanced nutrients digestibility and nitrogen balance. Rumen liquor reflected higher pH value in animals fed higher intake (NF) in the first two diets. Both feed intake and vitamin A levels enhanced volatile fatty acids and ammonia concentrations in the rumen liquor. Feed intake and vitamin A levels positively affected haemoglobin content, packed cell volume, glucose, urea, total protein, vitamin A, insulin, cholesterol, phospholipids, glutamate oxaloacetate and glutamate pyruvate transaminases and alkaline phosphatase in blood Vitamin A, insulin, cholesterol and phospholipids in blood increased gradually over the experimental period. Dressing percentages were 56.2, 49.6, 49.1 and 44.6% for the experimental groups, respectively. Liver content of glycogen and vitamin A increased with increasing feed intake and vitamin A levels. It is concluded that higher levels of vitamin A supplementation (than usually recommended) is required during fattening of lambs. Low energy and normal vitamin A levels are not recommended in lambs feeding. PMID- 1296562 TI - [Relationship between wool yield and cyst(e)ine level in blood plasma]. AB - Publications from Williams were the stimulation to study the relations between wool yield and cyst(e)ine concentration in blood plasma. Methodical experiments were carried out and the two methods used each provided clear results. At the same time the reversible binding of a part of the free cystine in the plasma with the plasma proteins and its effect on the analysis results might be considered. After an interpretation of the two methods their use is described taking into consideration the factors influencing the results of the analysis. It is concluded that the two methods are usable for the planned purpose. PMID- 1296563 TI - [Cold storage of wheat. 1. Ergosterol, ochratoxin A and citrinin after inoculation with Penicillium verrucosum]. AB - Seed wheat was inoculated without having been sterilized with an ochratoxin A and citrinin forming strain of Penicillium verrucosum and stored at moisture contents of 18, 20, 22, 24, and 26% at 10 and 4 degrees C. The production of ergosterol, a chemical indicator of fungal biomass, started within the storage time investigated (240 days). Only at 18% H2O/4 degrees C an increase of the ergosterol content was not observed. Ochratoxin A and Citrinin were not detected at 18% H2O/4 degrees C and 20% H2O/4 degrees C within 240 days (detection limit: 10 and 25 micrograms/kg, respectively). At the other combinations of moisture content and temperature the first detection of the two toxins approximately coincided with the onset of ergosterol production. With increasing moisture content and temperature the time up to the start of ergosterol production decreased, whereas the production rates of ergosterol, ochratoxin A and citrinin increased. Both toxins were produced with about the same rate during a first phase of accumulation. At 20-26% H2O there was no influence of moisture content and temperature on the relation between toxin content and the simultaneously reached ergosterol content. It is recommended that wheat highly contaminated with Penicillium verrucosum should not be stored beyond the start of ergosterol production. PMID- 1296564 TI - [Angioproliferative processes in gangrenous limbs]. AB - The results of the investigation of the limbs amputated because of the gangrene are presented. Soft tissues close to the gangrenous parts were examined, and in 26 of 100 samples examined angioproliferative processes with the formation of capillary foci were found. Proliferating capillaries grow into the surrounding tissues, including fibrous, muscular and adipose one. The process resembles somewhat neoplastic one: there is an infiltrative growth and mitotic activity. No similar alterations in the gangrenous tissue have been described so far. PMID- 1296565 TI - [Is localization of B-cells in the acini a normal condition or the sign of compensatory process in insulin-dependent diabetes mellitus?]. AB - 45 pancreatic biopsies from patients with insulin-dependent diabetes mellitus (IDDM), obtained in the process of surgical treatment were studied. A different degree of the Langerhans islands and morphological changes in B-cells was noted. The presence of endocrine-like cells in the acini and among the cells of the inter-acinar duct is of great interest. The granules of these cells were insulin positive when studied immunohistochemically this permitting one to consider them as B-cells. Further study of these cells will allow to deepen the knowledge about the mechanism of IDDM development and to improve the methods of treatment. PMID- 1296566 TI - [Lymphangion in health and in lymphedema]. AB - Comparative analysis of lymphangion construction in different organs and sites of human body is performed. Quantitative parameters of lymphangions (length, width, volume) are found to have age and site peculiarities. Myo-myocyte contacts of the nexus type and fascicular-reticular organizational principle of the cells underly myocyte association into functional syncytium. The valve consists of a muscleless fold and valvular bolster containing muscles. Restructuring of lymphangions in lower limb lymphedema are observed. In the course of the disease progression myocyte atrophy occurs which is followed by lymphangion wall collagenization. The alterations in lower limb lymphangions are proportional to the gravity of the disease. PMID- 1296567 TI - [Cytogenetics of neuroblastoma and glioma]. AB - Without having the common high specific marker, the tumours of the nervous system are, however, characterized by regular quantitative and structural changes of chromosomes. In this review molecular and genetic aspects of chromosome translocations typical for the main types of the nervous system, their role in activation of protooncogenes and their conversion to oncogenes, which is able to cause tumor transformation, are considered. Additionally, the role of chromosome translocation in the inactivation of suppressor genes is discussed. PMID- 1296568 TI - [Apropos of the article by V.V.Vlasjuk "Formulation of diagnosis, pediatric pathology, intrauterine infections" (Arkh. Pathol., 1991, No. 11, pp. 71-72)]. PMID- 1296569 TI - [Modification of the cellular and vascular reactions in the inflammatory focus by luteotropic hormone]. AB - Luteotropic hormone considerably alters the dynamics of experimental inflammation. A decrease of microvascular bed activation and the density of macrophage population are observed at early stages of the inflammation. Inhibition of fibroblast proliferative activity and acceleration of their differentiation are revealed during the period of reparation. The formation of the capsule went more intensely, but collagen synthesis was inhibited and fibrous tissue formed more slowly. The results obtained prove principal possibility of inflammation regulation by means of mediators and metabolites of the stress limiting systems. PMID- 1296570 TI - [Histochemical study of lesions in superficial and visceral candidiasis]. AB - Mycotic foci were studied histochemically on various experimental models of candidiasis. NAD-H, NADP-H-diaphorase, acid phosphatase and ATPase were revealed in the fungi, the activity of these enzymes depended on the state of the fungus. Diaphorase activity in the mucous membrane epithelium falls only if it is damaged by massive invasion of pseudo-mycelium. Inhibition of the enzyme activity in the visceral foci (kidney, liver, heart) occurs only in case of pronounced destruction and is not observed at the distance from the fungi. The results do not confirm the idea of fungal secretion of mycotoxins penetrating into the surrounding tissues and damaging them. PMID- 1296571 TI - Neutral glycolipid abnormalities in a t-complex mutant mouse embryo. AB - The content of neutral glycolipids was studied in normal and twl/twl mutant mouse embryos at embryonic day 11 (E-11). The twl mutation is part of the T/t complex on chromosome 17 and causes embryonic lethality from defects in the developing neural tube. Previous studies suggested that the mutation could involve a defect in ganglioside biosynthesis. Although the total neutral glycolipid content was similar in the normal and mutant whole embryos (approximately 80 nmol glucose/100 mg dry weight), marked differences were detected for the distribution of specific glycolipids. The content of lactosylceramide, globotriaosylceramide, and globotetraosylceramide was significantly higher in the mutant than in the normal embryos, whereas that of glucosylceramide was significantly reduced. The Forssman glycolipid was slightly elevated. The neutral glycolipid composition was similar in embryonic head and body regions of normal embryos, suggesting that the glycolipid abnormalities observed in the mutants are expressed in most embryonic cells and tissues. These and the previously reported ganglioside abnormalities in the twl/twl mutants could result from an inherited defect in glycolipid biosynthesis. PMID- 1296572 TI - X-linked glucose-6-phosphate dehydrogenase (G6PD) and autosomal 6 phosphogluconate dehydrogenase (6PGD) polymorphisms in baboons. AB - Electrophoretic polymorphisms of glucose-6-phosphate dehydrogenase (G6PD) and 6 phosphogluconate dehydrogenase (6PGD) were examined in captive colonies of five subspecies of baboons (Papio hamadryas). Phenotype frequencies and family data verified the X-linked inheritance of the G6PD polymorphism. Insufficient family data were available to confirm autosomal inheritance of the 6PGD polymorphism, but the electrophoretic patterns of variant types (putative heterozygotes) suggested the codominant expression of alleles at an autosomal locus. Implications of the G6PD polymorphism are discussed with regard to its utility as a marker system for research on X-chromosome inactivation during baboon development and for studies of clonal cell proliferation and/or cell selection during the development of atherosclerotic lesions in the baboon model. PMID- 1296573 TI - Antithrombin III (AT3) polymorphism in the marsupial Monodelphis domestica: identification and genetics. AB - Antithrombin III polymorphism was observed in the gray short-tailed opossum, Monodelphis domestica, by either one-dimensional polyacrylamide gel electrophoresis (PAGE; pH 7.9), two-dimensional PAGE (agarose, pH 5.4; 12% T, pH 7.9), or isoelectric focusing (pH 4.2-4.9) followed by immunoblotting with rabbit antiserum to human antithrombin III. Family studies demonstrated an inheritance of three codominant autosomal alleles, AT3A, AT3B, and AT3C, and a population study revealed frequencies of 0.70, 0.10, and 0.20, respectively. PMID- 1296574 TI - Dipeptidase-C in Drosophila melanogaster: genetic, ontogenetic, and tissue specific variation. AB - Dip-A, Dip-B, and Dip-C constitute structural genes for three peptidic enzymes in Drosophila melanogaster distinct from the leucine aminopeptidases. Their ontogenetic and tissue distributions of activities suggest the involvement of these enzymes in a general metabolic role, such as the regulation of amino acid and oligopeptide pools to make amino acids available for protein synthesis. Screening of chromosome substitution isogenic lines for DIP-C activity indicated that, like DIP-A and DIP-B, unlinked activity modifiers exist for Dip-C. The developmental profiles of dipeptidase activities are very similar, except in the pupal stage, during which DIP-C activity is markedly low compared to the other two enzymes. Intercorrelations of dipeptidase activities vary ontogenetically, which is consistent with the need for coordinate expression of these enzymes during certain developmental stages. Tissue-specific expression of dipeptidases in larvae and adults are also similar, although the relative levels of DIP-A activity differ from those of DIP-B and DIP-C in certain organs and body parts. Some of the differences among chromosome substitution lines for dipeptidase activities appear to be systemic, while others are developmental stage-specific and tissue-specific. Second- and third-chromosome variants for DIP-C activity differed in their tissue distribution. This is consistent with the presence of temporal and spatial variants in natural populations for other Drosophila enzymes. PMID- 1296575 TI - Analysis of isozyme loci in the face fly, Musca autumnalis DeGeer. AB - Vertical polyacrylamide gel electrophoresis was used to resolve enzymes at 50 putative loci in Iowa face flies, a recently arrived, colonizing, Palearctic species. Sixty-two percent of the 50 loci were polymorphic. The mean number of alleles per polymorphic locus was 3.2 +/- 1.38; the mean among all loci was 2.38 +/- 1.62 alleles. The effective number of alleles among 50 loci was 1.4 +/- 0.62. Mean observed and expected heterozygosities for the 50 face fly loci were 0.167 +/- 0.037 and 0.186 +/- 0.031, respectively. Comparison of the electrophoretic data for Musca autumnalis and for M. domestica L. showed similar high levels of gene diversity. A survey of gene diversity at 12 loci among six geographically independent laboratory colonies demonstrated statistically significant genetic differentiation that was probably due to drift after colonization. PMID- 1296576 TI - Molecular and biochemical elucidation of a cellular phenotype characterized by adenine analogue resistance in the presence of high levels of adenine phosphoribosyltransferase activity. AB - A mouse embryonal carcinoma cell line isolated for resistance to the adenine analogue 2,6-diaminopurine (DAP) was found to have near-wild-type levels of adenine phosphoribosyltransferase (APRT) activity in a cell-free assay. This DAP resistant (DAPr) cell line, termed H29D1, also exhibited near-wild-type levels of adenine accumulation and the ability to grow in medium containing azaserine and adenine. Growth in this medium requires high levels of intracellular APRT activity. Using the polymerase chain reaction (PCR) and the dideoxy chain termination sequencing technique, an A-->G transition was discovered in exon 3 of the aprt gene in H29D1. This mutation resulted in an Arg-to-Gln change at amino acid 87 of the APRT protein that, in turn, resulted in a decreased affinity for adenine. An increased sensitivity of APRT to inhibition by AMP was observed when comparing H29D1 to P19, the parental cell line. Using a transgene containing the A-->G mutation, we demonstrated that this mutation is responsible for the biochemical and cellular phenotypes observed for the H29D1 cell line. The approach used in this study provides a definitive method for linking a mutation to a specific cellular phenotype. PMID- 1296578 TI - A triangular cutting arteriotomy scissors facilitating end-to-side anastomoses. AB - A new microsurgical triangular cutting scissors facilitating end-to-side anastomoses has been developed. The instrument removes oval pieces of tissue from the vascular wall with a single cut. This has several advantages over conventional double cuts with straight microscissors. Preferential use of end-to side anastomoses has been advocated by several authors, one of the main reasons for this being preservation of the distal blood flow in the artery used in the recipient bed. It also has been reported that vascular occlusions are less frequent with this type of coupling. Another important indication for end-to-side anastomoses is a significant discrepancy in vessel size. One of the more demanding tasks in making an end-to-side anastomosis is the performance of a perfect arteriotomy. With the aim of facilitating the arteriotomy in end-to-side anastomoses, a new microsurgical instrument has been developed. PMID- 1296577 TI - Two-dimensional electrophoretic protein patterns of reciprocal hybrids of the mouse strains DBA and C57BL. AB - Two-dimensional electrophoretic patterns of cytoplasmic liver proteins of the mouse were investigated in reciprocal hybrids of the two inbred mouse strains DBA and C57BL in order to establish whether strain-specific protein variants reveal a mode of inheritance compatible with the concept of genomic imprinting. Variants of this type were found to account for about 11% of approximately 200 variant protein spots scrutinized. Transmission of the maternal form of a variant protein was more frequent than transmission of the paternal form. Maternal/paternal transmission was observed only for proteins showing strain variations in their amount. The results are discussed in terms of the frequency of imprinted genes. PMID- 1296579 TI - Alfentanil increases intracranial pressure when intracranial compliance is low. AB - Intracranial pressure increases following the administration of alfentanil 1 mg are reported in five patients with suspected normal pressure hydrocephalus who were undergoing infusion of saline into a lateral ventricle to measure cerebrospinal fluid outflow resistance. The increase in intracranial pressure was accompanied by a fall in mean arterial pressure. These observations show that, when the intracranial compliance is reduced, alfentanil can cause considerable increases in intracranial pressure and decreases in cerebral perfusion pressure. PMID- 1296580 TI - Factors associated with pediatricians' participation in Medicaid in North Carolina. AB - OBJECTIVE: To describe the relative importance of factors influencing pediatricians' participation in Medicaid in North Carolina. DESIGN: Questionnaire survey. SETTING AND PARTICIPANTS: Nonacademic primary care pediatricians in direct patient care at least 50% of the time; 332 (85%) of the 389 eligible pediatricians responded. MAIN OUTCOME MEASURES: Proportion of pediatricians who restricted Medicaid patients' access to their practices. The association between restricting access and the following factors was assessed: Medicaid reimbursement, pediatricians' demographic characteristics, knowledge of the Medicaid program, attitudes toward Medicaid patients and the Medicaid program, and beliefs about whether other physicians were available to care for Medicaid patients. RESULTS: Twenty-nine percent of pediatricians restricted Medicaid patients' access to their practices. The proportion of pediatricians restricting access was 62% in cities, 13% in medium-sized towns, and 12% in small towns (P less than .001), but the proportion of pediatricians in cities who restricted access varied from 87% to 22%. Pediatricians who received a higher proportion of their usual fee were less likely to restrict Medicaid patients' access. The relationship between Medicaid payment and restricted access was substantially weakened after controlling for the following factors: (1) the size of the community, (2) pediatricians' attitudes toward Medicaid payment, (3) their perceptions that they were too busy to care for Medicaid patients, and (4) whether there were other resources for the care of Medicaid patients. At comparable levels of payment, rural pediatricians were about six times less likely than urban pediatricians to restrict access. Pediatricians who knew less about Medicaid reimbursement also restricted access more often. Whether or not they restricted access to new Medicaid patients, pediatricians provided acute, preventive, hospital, and emergency care to the Medicaid patients who were already in their practices. CONCLUSIONS: Existing resources for the care of Medicaid patients, pediatricians' economic dependence on Medicaid, and the local norms of practice may be important factors in pediatricians' decision to participate in Medicaid. Increasing reimbursement will have only modest effects on Medicaid participation. Strategies to improve participation should also address pediatricians' knowledge of the Medicaid program and enlist the support of community physicians. PMID- 1296581 TI - Seronegative generalized myasthenia gravis: low frequency of thymic pathology. AB - We have reviewed thymus histology, preoperative serum acetylcholine receptor antibody status, and clinical features of all 50 patients who underwent thymectomy for generalized myasthenia gravis in the University of British Columbia-affiliated hospitals over the last 8 years. Seven patients had thymoma, 25 had hyperplasia, and 18 had a normal thymus. The seven thymoma patients all had severe limb involvement and all had circulating antibodies against the acetylcholine receptor. Patients without circulating antibodies had only minimal limb involvement and half of them had a normal thymus. Only two of the 32 (6%) patients with abnormal thymus were antibody-negative; this contrasts with six of the 18 patients (33%) with normal thymus. We conclude that seronegative patients with generalized myasthenia gravis constitute a distinct subgroup which may not be immunologically homogeneous and could be subgrouped with normal or abnormal thymic histology. PMID- 1296582 TI - Recurrent encephalopathy and seizures in a US native with HTLV-I-associated myelopathy/tropical spastic paraparesis: a clinicopathologic study. AB - A patient with progressive spastic paraparesis originally ascribed to multiple sclerosis developed recurrent encephalopathy and seizures. A diagnosis of HTLV-I associated myelopathy/tropical spastic paraparesis was established prior to death. Autopsy confirmed chronic inflammatory myelopathy and active inflammation in the white matter of the temporal lobes. PMID- 1296583 TI - Circumferential aortic dissection in a young woman. PMID- 1296584 TI - Scleral buckle with diathermy for simple retinal detachments. 100 pneumatic retinopexy eligible eyes. AB - One hundred consecutive pneumatic retinopexy eligible eyes underwent outpatient scleral buckle and diathermy. Follow-up averaged 31 months. Four cases required a second operation. Absence of an encircling band was the only significant risk factor (P = 0.00000028) for the three redetachments because of new or missed retinal tears. Although 18 patients had some other disease that reduced visual acuity before the retina detached, final visual acuity was 20/40 or better in 79 patients. Matched with a reported series treated by pneumatic retinopexy with cryopexy, these scleral buckle with diathermy cases exhibit significantly better final visual acuity with fewer major complications. The final acuity is also better than for two similar series, one treated with temporary balloon buckle and the second with scleral buckle and cryopexy. Use of diathermy rather than cryotherapy in the zone of retinal detachment may be the reason for the current group's better final acuity results. PMID- 1296585 TI - Towards the 21st century: provision of battlefield surgical care. PMID- 1296586 TI - GPs' diagnosis and management of the discharging ear. PMID- 1296587 TI - Pneumosinus dilatans and arachnoid cyst: a unique association. PMID- 1296588 TI - Tuberculous abscesses in patients with AIDS. AB - Five cases of large tuberculous abscesses in patients with AIDS were observed over a 2-year period at the New York Veterans Affairs Medical Center. These cases represent 11.6% of the 43 cases of tuberculosis diagnosed in patients with AIDS during that period. The abscesses were located in the liver, abdominal wall, psoas muscle, mediastinum, and peripancreatic area. All patients presented with localized pain or swelling, and four of five patients had fever. The diagnosis was made on the basis of detection of abscesses on computed tomography (CT) and the results of culture of abscess material obtained by CT-guided aspiration. CT guided therapeutic drainage was performed in two cases. Despite administration of therapy, two of five patients died of tuberculous infection. Formation of tuberculous abscesses appears to be a common complication of tuberculosis in patients with AIDS. This diagnosis should be considered for patients with AIDS who have fever and localized pain or swelling. PMID- 1296589 TI - Which hormone tests for the diagnosis of polycystic ovary syndrome? AB - OBJECTIVE: To assess the frequency of abnormal values for hormone measurements commonly used in the biochemical diagnosis of polycystic ovary syndrome (PCOS). DESIGN: Hormone measurements in 63 unselected women with clinical and ultrasound diagnosis of PCOS attending gynaecological and general endocrine clinics in a District General Hospital were compared with those from a group of 20 normal ovulatory controls in the early follicular phase of their cycles. MEASUREMENTS: Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH ratio, total testosterone, derived free testosterone, sex hormone binding globulin, androstenedione, and dehydroepiandrosterone (DHEA) were measured by radioimmunoassays. LH and FSH measured by two different assays. RESULTS: The mean serum LH and LH/FSH ratio were significantly (P less than 0.01) higher in the women with PCOS compared with the normal group, but these two measurements were in the abnormal range for only 35% and 41-44%, respectively. Absolute gonadotrophin values were significantly different using the two assay methods, which employed the same reference preparation as standard. Mean serum total testosterone concentration was significantly higher in the PCOS group and was the most frequently (70%) abnormal biochemical marker for PCOS. Sex hormone binding globulin (SHBG) did not differ significantly between the two groups but showed a negative correlation with body mass index in women with PCOS. The combination of SHBG and testosterone to derive a free testosterone value did not further aid the biochemical diagnosis of PCOS. Androstenedione was significantly higher in the PCOS group than in the control group, with a frequency of 53%. There was no significant difference in DHEA-S between the two groups. CONCLUSION: When typical ovarian ultrasound appearances plus the clinical features of oligomenorrhea and/or hirsuitism were used to define PCOS total testosterone was the best single hormonal marker of the condition. Testosterone, androstenedione or LH, either alone or in combination, were raised in 86% of women with PCOS and these should be the definitive hormonal tests. Using LH/FSH ratio as a biochemical criterion for diagnosis of PCOS should be abandoned because of its low sensitivity. To be of value the normal range for all hormones should be precisely defined in a group of regularly ovulating women in the early follicular phase of the cycle for the assay used in each laboratory. PMID- 1296591 TI - The National Practitioner Data Bank. Report from the first year. PMID- 1296590 TI - Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. AB - PURPOSE: A multicentric randomized study that compared patients who received intrahepatic arterial infusion (HAI) to a group of patients who did not receive HAI (control group) was performed for unresectable hepatic metastases from primary colorectal carcinoma. PATIENTS AND METHODS: One hundred sixty-six patients were assigned randomly to HAI of floxuridine (5 fluoro-2'deoxyuridine [FUDR]) 0.3 mg/kg/d for 14 days every 4 weeks or to the control group; this latter group, depending on the investigator's choice, was either under observation or received systemic fluorouracil (5-FU). The same regimen of systemic 5-FU also was administered to the HAI group in the event of extrahepatic progression. No crossover from the control group to the HAI group was permitted. The mean duration of follow-up was 54 months (range, 31 to 72), and 163 patients were analyzed. RESULTS: A significant improvement was observed in the survival rate for the 81 patients assigned to HAI group (P less than .02) with a 1-year survival rate of 64% versus 44% in the control group (82 patients). The 2-year survival rate was 23% versus 13%. The median survival was 15 months versus 11 months for the HAI group and the control group, respectively. Survival was better for patients with a less than 30% liver involvement, and for those treated in more specialized centers. The hepatotoxic effects of HAI were observed in 47 patients (chemical hepatitis [n = 28], and biliary sclerosis [n = 19]). The 1 year rate of sclerosing cholangitis was equal to 25%. Gastrointestinal toxicity was infrequent and consisted of gastritis or diarrhea. CONCLUSIONS: Therapy with HAI of FUDR improves the survival of patients with liver metastases over colorectal carcinoma. However, the methods that are used to diminish the toxicity of HAI and efficient systemic chemotherapy, such as a combination of 5-FU and leucovorin, are required to prevent extrahepatic metastases. PMID- 1296592 TI - Performance characteristics of a 511-keV collimator for imaging positron emitters with a standard gamma-camera. AB - Line-source experiments were conducted to assess the performance of a gamma camera equipped with a specially designed 511-keV collimator for the planar imaging of positron emitters. The results were compared with the camera performance with routinely used collimators and radionuclides (thallium-201, technetium-99m and gallium-67). With positron emitters, scatter contributed less to the widening of the line spread function than with radionuclides emitting lower photon energies. These observations can be explained by the relative deterioration in the discrimination power of the gamma-camera to reject scattered radiation at low energies. Planar 511-keV imaging may provide relevant clinical information, as we showed by fluorodeoxyglucose studies in a patient with a myocardial infarction and in a patient with a malignant lymphoma. It is concluded that positron emitters can be effectively applied for planar imaging with the generally available gamma-cameras. This study implies that radiotracers developed for positron emission tomography may find a place in the practice of conventional nuclear medicine. PMID- 1296593 TI - Variability in consultation rates and practitioner level of diagnostic certainty. AB - BACKGROUND: This study was designed to determine the variability in the consultation practices of family physicians and family nurse practitioners in an urban group practice, and to examine the relation between the referring practitioner's diagnostic certainty at the time of the consultation request, the specificity of the request to the consultant, and the frequency with which the practitioner ordered consultations in that specialty. METHODS: This study examined consultations requested by six family physicians and two family nurse practitioners that were directed to nine medical and surgical specialties in connection with 35,218 family practice visits made over a 19-month period in an urban family practice. Requests for consultation were scored based on the level of certainty of the referring practitioner's diagnosis at the time of consultation and the specificity of the consultation request. RESULTS: There was nearly a fivefold variation in the overall specialty consultation rates among providers, with even greater variation in each individual specialty area studied. Referral rate correlated positively with certainty of diagnosis (r = .40). There was no consistent relation between request specificity and referral rate. CONCLUSIONS: Consultation rates vary widely, even among family physicians and nurse practitioners within the same practice. The rate at which a practitioner orders consultations in a specialty area increases in relation to the practitioner's certainty of the diagnosis at the time the consultation was requested. Diagnostic certainty is discussed as a possible indicator of a referring practitioner's knowledge in a specialty area, implying that the greater a practitioner's knowledge in a specialty area, the more he or she consults with specialists in the field. Financial incentives that attempt to decrease specialty consultation should be reexamined in light of these findings. PMID- 1296594 TI - Obstetrics and gynecology. PMID- 1296595 TI - Be cautious in the use of NSAIDs. PMID- 1296596 TI - Big money for big ideas: medical research in Texas. PMID- 1296598 TI - Nil by mouth after midnight? PMID- 1296597 TI - Multidrug-resistant tuberculosis. PMID- 1296599 TI - RACDS and ANZCA policy on sedation for dental procedures. PMID- 1296600 TI - Spinal cord compression from epidural metastases. PMID- 1296601 TI - July 6 deadline for compliance with all provisions of OSHA regs. PMID- 1296602 TI - Mitral valve prolapse: two dimensional echocardiography reveals a high prevalence in three to twelve year old children. AB - The prevalence of mitral valve prolapse (MVP) appears to be age related, MVP being commoner in children as compared to adults. This suggests that asymptomatic MVP may be most frequent in children who are very young. In this study, to better define the prevalence of MVP in young children, we used two dimensional echocardiography and prospectively surveyed 213 healthy urban school children between 3 and 12 years of age. MVP was diagnosed when prolapse of mitral leaflet/s was demonstrated by both two-dimensional and M-mode echocardiography at parasternal long-axis views. Overall, MVP was found in 28 of 213 (13.1%) children. MVP was similarly prevalent in all age groups studied (3-5.9 years: 13 of 83 (13.5%); 6-8.9 years: 9 of 71 (11.2%); and 9-12 years: 6 of 31 (16.2%) children; Chi square = 0.57, p greater than 0.5). Univariate analysis showed that the prevalence of MVP was independent of sex, birth weight, resting heart rate and systolic or diastolic blood pressure. A mid systolic murmur was present in 50.6% of the children although it correlated with echocardiographic diagnosis of MVP in only 39.3%. The left ventricular size or wall thickness and mitral EF and DE slopes were similar in children either with or without MVP. Our results indicate that asymptomatic MVP is frequent in children upto 12 years of age. As a diagnostic test of MVP, presence of apical systolic murmur is considerably inferior to echocardiography. No morphological left ventricular correlates were identified in MVP. PMID- 1296603 TI - Alternative models for specialty nursing practice. AB - Specialization in nursing dates from the early part of the twentieth century. Since 1925 the specialty movement has escalated, and the specialty programs have been moving to the master's degree level. There are two different models for specialization: One is the nursing model that focuses on advanced content from the behavioral sciences, education, and nursing. The specialists who use the nursing model focus on the caring role of the nurse. The specialists who follow the other model, the collaborative model, bring their nursing skills with them, and they acquire advanced knowledge of medicine and the behavioral and biological sciences. They work closely with physicians, diagnosing and treating patients. Most of the specialists within the collaborative model are covered by an additional level of state certification or licensure. PMID- 1296604 TI - Reference values of normal cerebrospinal fluid composition in infants ages 0 to 8 weeks. PMID- 1296605 TI - Reducing the mortality from abdominal aortic aneurysms: need for a national screening programme. PMID- 1296606 TI - A randomized controlled trial of perioperative rifampin/trimethoprim in cerebrospinal fluid shunt surgery. AB - A randomized, double-blind, placebo-controlled trial of perioperative rifampin trimethoprim was undertaken at the Hospital for Sick Children from March 1984 to October 1987, in which 243 patients undergoing 300 cerebrospinal fluid (CSF) shunting procedures were randomized into groups including treatment with rifampin/trimethoprim and placebo, and then followed for a minimum of 2 years. Patients were stratified prior to randomization into those with and those without meningo-myeloceles having first insertions of their shunts, and those having revisions. Patients could be entered into the study more than once, but always received the same treatment regimen once allocation had taken place. Among the patients receiving antibiotics there was an infection rate of 12%, versus 19% among patients receiving placebo. Among the surgical procedures, the rates were 9% and 15%, respectively. Because these rates of infection were a substantial increase over the rate of 7.5% overall for the few years prior to implementation of the study, and well over any acceptable rate of infection, the study was stopped before statistical significance was reached. However, had the study continued, and the proportions of patients becoming infected remained constant, we would have been able to achieve a statistically significant difference in rates of infection, and therefore demonstrate a benefit of rifampin/trimethoprim as prophylaxis against shunt infection. Methodological problems encountered in this and other studies of prevention of CSF shunt infection will be discussed. PMID- 1296608 TI - The readers' NIH. PMID- 1296607 TI - Percutaneous absorption of drugs. AB - The skin is an evolutionary masterpiece of living tissue which is the final control unit for determining the local and systemic availability of any drug which must pass into and through it. In vivo in humans, many factors will affect the absorption of drugs. These include individual biological variation and may be influenced by race. The skin site of the body will also influence percutaneous absorption. Generally, those body parts exposed to the open environment (and to cosmetics, drugs and hazardous toxic substances) are most affected. Treating patients may involve single daily drug treatment or multiple daily administration. Finally, the body will be washed (normal daily process or when there is concern about skin decontamination) and this will influence percutaneous absorption. The vehicle of a drug will affect release of drug to skin. On skin, the interrelationships of this form of administration involve drug concentration, surface area exposed, frequency and time of exposure. These interrelationships determine percutaneous absorption. Accounting for all the drug administered is desirable in controlled studies. The bioavailability of the drug then is assessed in relationship to its efficacy and toxicity in drug development. There are methods, both quantitative and qualitative, in vitro and in vivo, for studying percutaneous absorption of drugs. Animal models are substituted for humans to determine percutaneous absorption. Each of these methods thus becomes a factor in determining percutaneous absorption because they predict absorption in humans. The relevance of these predictions to humans in vivo is of intense research interest. The most relevant determination of percutaneous absorption of a drug in humans is when the drug in its approved formulation is applied in vivo to humans in the intended clinical situation. Deviation from this scenario involves the introduction of variables which may alter percutaneous absorption. PMID- 1296609 TI - Organic mental disorders. PMID- 1296610 TI - Prevalence of Plesiomonas shigelloides among diarrhoeal patients in Bangladesh. AB - The incidence of Plesiomonas shigelloides among diarrhoeal patients attending the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) from January through December 1987, has been reported. Using bile peptone broth (pH 8.8) as an enrichment medium and Salmonella-Shigella agar to isolate the organism, P. shigelloides was isolated from 838 (6.4%) of 13,142 patients, 523 (4.0%) of whom had no other pathogen isolated. The percentage of isolation was higher from stool (9.2%) than from rectal swab (5.9%) specimens (P < 0.005). The incidence of P. shigelloides was higher among male (64.0%) than female (36.0%) patients (P < 0.005). Isolation was highest among children less than five years. P. shigelloides was isolated most often in March (11.0%) and September (7.7%), indicating two seasonal peaks of incidence before and after the monsoons. All the strains were uniformly sensitive to chloramphenicol, furazolidon, gentamicin and trimethoprim-sulfamethoxazole. Sensitivity of the organism to ampicillin and tetracycline was 27.0% and 89.0%, respectively. This indicates that P. shigelloides may be an important agent of diarrhoea in our patient population. PMID- 1296611 TI - Inhibition of target cell adhesion by monoclonal antibody to the 66 kD surface antigen of Entamoeba histolytica. AB - The adherence of Entamoeba histolytica trophozoites to target cells was studied using a monoclonal antibody to a major surface antigen of 66 kD. Preincubation of trophozoites with monoclonal antibody decreased their ability to adhere to and engulf erythrocytes and to destroy Chinese hamster ovary cells. The monoclonal antibody was specific for the 66 kD antigen, which is possibly a major participant in the adhesion that precedes phagocytosis and cytopathic effects. PMID- 1296612 TI - Widespread granuloma annulare and cervical adenocarcinoma. PMID- 1296613 TI - Basal cell carcinoma in North American blacks. PMID- 1296615 TI - Reversible motor neuron disease. PMID- 1296614 TI - Motor neuron disease model. PMID- 1296616 TI - Botulinum toxin and dysphagia. PMID- 1296617 TI - Overtreatment of neonates? A personal retrospective. PMID- 1296618 TI - Meal frequency and the thermic effect of food. PMID- 1296619 TI - When do cardiovascular parameters return to their preconception values? PMID- 1296620 TI - Repeated intracervical instillation of prostaglandin E2 efficacy and safety. PMID- 1296621 TI - Pancreatic abscess due to Candida albicans. PMID- 1296622 TI - Spotlight article: effect of backrest position on mixed venous oxygen saturation in patients with mechanical ventilation after coronary artery bypass surgery. (Noll ML, Fountain RI. Heart Lung 1990; 19:243-51.) PMID- 1296623 TI - HIV infection, confidentiality and discrimination. PMID- 1296624 TI - Gastrointestinal damage associated with nonsteroidal antiinflammatory drugs. PMID- 1296625 TI - Arteriotomy scissors. PMID- 1296626 TI - Steroid treatment in giant cell arteritis. PMID- 1296627 TI - Reflux of air or barium into the biliary ducts. PMID- 1296628 TI - Statistical analysis of crossover studies. PMID- 1296629 TI - Rat bites and diabetic foot ulcer. PMID- 1296630 TI - Intuition and the nursing process. PMID- 1296631 TI - Pediatricians participating in Medicaid. PMID- 1296632 TI - Frontal sinusitis. PMID- 1296633 TI - More on minister's masterpiece. PMID- 1296634 TI - Prenatal screening for Down's syndrome. PMID- 1296635 TI - The American health care system--managed care. PMID- 1296637 TI - Meningismus defined. PMID- 1296636 TI - Comment on Bruera et al., Local toxicity with subcutaneous methadone. Experience of two centers, Pain, 45 (1991) 141-143. PMID- 1296638 TI - Biologic wound coverings in burn treatment. PMID- 1296639 TI - Culture and antigen detection tests for streptococcal tonsillopharyngitis. PMID- 1296640 TI - Nuts, nuts good for your heart...? PMID- 1296641 TI - SOAP or HOAP. PMID- 1296642 TI - Prevalence of carotid artery lesions in renal fibromuscular dysplasia. PMID- 1296643 TI - Differential diagnosis of otitis media and externa. PMID- 1296644 TI - Postcoital contraception. PMID- 1296645 TI - Intradermal vaccination for hepatitis B. PMID- 1296646 TI - Propofol infusion in children. PMID- 1296647 TI - Unexplained death in fit young people. PMID- 1296648 TI - Screening for abdominal aortic aneurysms. PMID- 1296649 TI - Early analgesia for acute abdominal pain. PMID- 1296650 TI - The National Practitioner Data Bank: bane or benefit? PMID- 1296651 TI - Self-prescribing: ill-advised? PMID- 1296652 TI - UTHC-Tyler bolsters state's medical research effort. PMID- 1296653 TI - When are tongue depressors regulated waste? PMID- 1296654 TI - Right-heart pulmonary emboli-in-transit. PMID- 1296655 TI - POINTER correctly estimates the transmission probabilities under the general transmission model in the case of incomplete selection. PMID- 1296656 TI - Molded acrylic mouthguard to control bleeding at the hard palate graft site after eyelid reconstruction. PMID- 1296657 TI - Theophylline poisoning. PMID- 1296658 TI - The use of animals in medical education. PMID- 1296659 TI - Typical changes in the viscerocranium in acromegaly. PMID- 1296660 TI - Cause of wild dog death. PMID- 1296661 TI - Unipolar coagulation in colon angiodysplasia. PMID- 1296662 TI - Basic life support training. PMID- 1296663 TI - Patient-controlled analgesia--a serious incident. PMID- 1296664 TI - Erythropoietin and platelet production. PMID- 1296665 TI - Ice man: victim of prehistoric schnapps? PMID- 1296666 TI - Thrombolytic treatment for elderly patients. PMID- 1296667 TI - An epidemiological perspective of injuries in the Northwest Territories. AB - This paper reviews the epidemiology of injuries in the multiethnic population of the Northwest Territories (NWT), Canada, based on mortality, hospital morbidity, and health survey data. Overall, injury mortality in the NWT has remained consistently higher than the Canadian national rate. In the NWT, an increasing trend was observed for motor vehicle accidents and homicide in both sexes, and suicide among males, while other accidents (including fires and drowning) have declined substantially among males. The age group which reported the highest suicide rate was shifted downward between the periods 1961-70 and 1981-86. Of the three major groups in the NWT, the overall injury mortality rate was comparable between Indians and Inuit, and their rates were twice as high as that of non Natives. The age-standardized hospitalization rate for all injuries for the Keewatin Region was similar to that of Canada as a whole whereas the rate for the entire NWT was about twice as high. In the NWT, age-specific hospitalization rate was highest in both sexes among the elderly (age 65+), followed by those in age group 15-24. A survey of a random sample of Keewatin Region residents indicated a low usage rate for seatbelts and helmets while a significant minority of drivers (18%) admitted to drinking and driving sometimes. Such data contribute to a more comprehensive assessment of the burden of injury mortality and morbidity, an important prerequisite for the investigation of risk factors and design of intervention programs. PMID- 1296668 TI - Septal neurons related with hippocampus increase their firing rate after long term clomipramine. AB - In the rat, long-term clomipramine increases the firing rate in lateral septal neurons. Although the hippocampus is the main afference for septal nuclei, it is unknown whether clomipramine increases the firing rate in most of hippocampal septal neurons. Therefore, the present study explored the actions of long-term clomipramine in lateral septal neurons identified by their relation to the hippocampus. In most recordings, hippocampal stimulation produced a brief excitatory short-latency response, followed by a period of inhibition of firing. These neurons increased their firing rate after clomipramine treatment. Other septal neurons not respondent to hippocampal stimulation did not respond to clomipramine treatment, either. We concluded that only hippocampal-septal neurons are clomipramine responders too, and the drug-induced enhancement of firing rate is likely to be mediated by an interneuron-mediated disinhibition process. PMID- 1296669 TI - Effects of nimodipine on multiunit activity of several brain structures following acute global cerebral ischemia-anoxia in cats. AB - The effects of nimodipine, a 1,4-dihydropyridine calcium channel blocker, on multiunit activity (MUA) of several brain structures were investigated in cats during 6 h immediately following acute global cerebral ischemia-anoxia induced by a 10 min cardiorespiratory arrest (CRA), as well as in cats exposed to sham procedures corresponding to CRA. Four groups of cats were studied: 1) CRA and continuous administration of nimodipine, 1 microgram/kg/min iv during 6 h; 2) CRA and continuous administration of vehicle; 3) sham and continuous administration of nimodipine as in group 1; 4) sham and vehicle as in group 2. MUA and electroencephalogram disappeared during ischemia-anoxia; their progressive recovery occurred throughout the hours following CRA, although 6 h after CRA MUA was still lower than its control prearrest values in all the recorded subcortical structures. Delta-like waves, isolated spikes, and bursts of fast EEG waves occurred during the recovery of EEG activity. Nimodipine inhibited the otherwise increasing MUA in mesencephalic reticular formation, hippocampus and putamen, but not in ventromedial hypothalamus, during the hours following acute global cerebral ischemia-anoxia. Absence of isolated spikes and bursts of fast EEG activity was noted in the EEG of CRA-, nimodipine-treated cats. Nimodipine significantly reduced MUA in hippocampus but not in other cerebral structures in cats of the sham treated group. The results suggest the involvement of 1,4 dihydropyridine sensitive calcium channels in the cellular mechanisms related to neuronal activity after cerebral ischemia-anoxia, and the possible relationship between the effects of nimodipine on MUA and better functional conditions of the central nervous system after acute global cerebral ischemia-anoxia. PMID- 1296670 TI - Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. AB - In cerebral cortex and lateral septal nuclei different serotonergic receptor subtypes coexist, thus a different action on neuronal firing may be expected depending on the receptor activated. Dorsal raphe nucleus stimulation produced an increased rate of firing in cortical layer V, and in lateral septal nuclei. However, firing rate in cortical layer VI remained unchanged after stimulating the dorsal raphe nucleus. Clomipramine is a tricyclic which exerts its main actions on serotonergic receptors, and long-term treatment with this antidepressant produced a selective increased firing rate in lateral septal neurons, but not in cortical neurons. From an electrophysiological point of view, it is concluded that the excitatory actions on firing rate elicited by dorsal raphe nucleus stimulation or clomipramine treatment are mediated by 5-HT2 receptor subtype activation which is likely to be acting as a 5-HT1A modulator in such places where both receptor subtypes coexist. PMID- 1296671 TI - The importance of employing homologous serum free of thyronines in radioimmunoassays to assess circulating thyroid hormones in rainbow trout. AB - Although abundant, available information regarding the values of circulating thyronines in the rainbow trout is misleading and confusing. The present study demonstrates the importance of maintaining species serum-homology when measuring thyronines with RIA to avoid spurious results. The utilization of homologous (trout) serum free of thyronines in the standard curve allowed the standardization of accurate and specific radioimmunoassays to quantitate circulating T3 and T4 levels in 10 microliters of rainbow trout serum. Detection limit was 50 pg for both thyronines. Inter- and intra-assay coefficients of variation were minor to 10%. Mean values for T3 and T4 +/- SEM in the trout population studied (n = 34) were 23.6 +/- 1.2 and 12.0 +/- 2.3 ng/ml respectively. A positive and significant correlation (p < 0.005) between body weight and T3 was observed, confirming the active participation of this thyronine in growth processes. PMID- 1296672 TI - Rapidly recurring cortical seizures induce changes in neuronal responsiveness to acetylcholine. AB - The majority of mechanisms proposed to explain epileptic discharge suggest an excessive synaptic input into the cell or possible changes in cellular excitability which result in a decreased firing threshold and in the presence of self-sustained activity. It is likely that these changes are caused by modifications in the membrane receptor sensitivity to a specific neurotransmitter. In view of the above, the purpose of the present study has been to evaluate the sensitivity of the postsynaptic receptor by means of the microiontophoretic applications of substances whose pharmacological effect is known, thus determining its possible involvement in the epileptic process. Changes in cortical excitability were induced by electric stimuli in the sensorimotor cortex of rats anesthetized with urethane (1 g/kg intraperitoneally), immobilized with pancuronium bromide and kept alive with mechanical respiration. The electric stimuli consisted of trains of biphasic pulses, each lasting one millisecond, with a frequency of 100 pps and with a train duration of 1 second. The response of the neuron to acetylcholine was evaluated before and after the kindling had been established. The dosage was measured in nanoamperes of microiontophoretic ejecting current. Extracellular field potentials were recorded with the central barrel of 4-barrel micropipettes. Peripheral barrels were used for iontophoretic applications of Acetylcholine (Ach .1, 1M), Atropine (25mM). One of these barrels containing NaCl (2M) was used for the automatic passage of balancing current.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296673 TI - [PAHO in action today: the case of cholera]. PMID- 1296674 TI - [PAHO. In the beginning: 1902-20]. PMID- 1296675 TI - [PAHO. The Office in expansion: 1920-1946]. PMID- 1296676 TI - [PAHO. A regional call-to-arms: 1946-1958]. PMID- 1296677 TI - [PAHO. The right to health: 1958-1975]. PMID- 1296678 TI - [PAHO. Toward health for all: 1975-1983]. PMID- 1296679 TI - [PAHO. Health in development: 1983-1992]. PMID- 1296680 TI - ["The Bulletin of the PAHO": a health forum]. PMID- 1296681 TI - [Health and the environment]. PMID- 1296683 TI - [Frontal attack on malaria]. PMID- 1296682 TI - [The campaign against Aedes aegypti]. PMID- 1296684 TI - [The campaign against communicable diseases]. PMID- 1296686 TI - [National and local health systems]. PMID- 1296685 TI - [Improving the health of the population through planning]. PMID- 1296687 TI - [The crucial resource: health workers]. PMID- 1296688 TI - [Veterinary public health]. PMID- 1296689 TI - [Health through nutrition]. PMID- 1296690 TI - [Promoting research]. PMID- 1296691 TI - [Response to the health needs of mothers and children]. PMID- 1296692 TI - [The death of a disease]. PMID- 1296693 TI - [The campaign against poliomyelitis]. PMID- 1296694 TI - [Disease prevention through immunization]. PMID- 1296695 TI - [Acute respiratory infections]. PMID- 1296696 TI - [The campaign against cancer]. PMID- 1296697 TI - [Essential drugs available to all]. PMID- 1296698 TI - [Preparations for disasters]. PMID- 1296699 TI - [Health promotion]. PMID- 1296700 TI - [The campaign against AIDS]. PMID- 1296701 TI - [Health: a condition for development]. PMID- 1296702 TI - [Therapeutic perspectives on antisense oligonucleotides]. PMID- 1296703 TI - Effect of continuous, long-term administrations of acetylsalicylic acid on hematological and hemocoagulation changes in the rat. AB - Acetylsalicylic acid is currently being widely used either itself or in combination with the other substances for the prevention of thromboembolic events. Its effect is particularly given by the inhibition of the cyclooxygenase enzyme participating in the metabolism of eicosanoids. The recommended doses of acetylsalicylic acid as well as frequency of administrations are very different. The present work is aimed at estimating the effect of the continuous administration of acetylsalicylic acid for 28 days on hematological and hemocoagulation changes in the rat. The experimental results suggest that long term administrations of acetylsalicylic acid should be used cautiously in human medicine. They signalize the need of long-term, aimed clinical studies of hematological parameters of patients preventively treated with acetylsalicylic acid, also with respect to the producer of this substance. It is also impossible to neglect regular controls of necessary parameters for the estimation of the efficiency of the given therapy in each patient with respect to individual reactions. The dosage should also be adjusted with respect to the age, sex and individual sensitivity of the organism. PMID- 1296704 TI - [The bioavailability of nicorandil after oral administration of a single dose of 10 or 20 mg preparations]. AB - To evaluate the bioavailability of 4 different formulations of nicorandil, 10 mg and 20 mg (Bracco) versus 10 mg ang 20 mg (Merck), we have carried out a study involving 24 young healthy volunteers. The drug was administered in single oral dose and the plasma concentration levels were evaluated by HPLC method. From the results obtained, we have seen that both the 2 products of 10 mg (A and B) and the 2 products of 20 mg (C and D) are equivalent and have high relative bioavailability: it reaches the values of 96.5% (A versus B) and 120% (C versus D). As regards the 2 formulation of 20 mg, the results of bioavailability are confirmed by data obtained from dissolution study in vitro, where the dissolution is almost complete in 30 minutes. PMID- 1296705 TI - [A new cold sterilization chemical. I. Chemical characterization and mechanism of action]. AB - The equilibria relative to a cold sterilizer and their interactions were studied to verify how many active compounds were present in solution. Microbiological activity derived from chlorine, hydrogen peroxide and peroxymonosulfate which could react also with chloride ions present in biological fluids, developing active chlorine. PMID- 1296706 TI - Induction of endoreduplication in double minutes of the human neuroblastoma cells and the replication pattern. AB - Induction of endoreduplication (ERD) using Hoechst 33258 as well as colcemid was carried out in cultured neuroblastoma (NB) line cells. In these endoreduplicated cells, the majority of double minutes (DMs) appeared to take a diplochromosome like configuration to form a cluster consisting of four minute elements, assuming a complex DM. Sister chromatid differential staining (SCD) using 5-bromo-2' deoxyuridine (BrdUrd) revealed the non-random distribution of the stained chromatids among four chromatids composing each diplochromosome, suggesting the occurrence of so-called "outside replication" of DNA strands during the process of ERD. The same pattern of differential staining was also found in the quadruple minutes of each endoreduplicated DM. Since DMs are acentric, the present results suggest that centromeres do not play any essential role in the formation of diplochromosomes observed in the conventional cytologic preparations and that centromeres are probably not responsible for the phenomenon of the "outside replication" of DNA strands. PMID- 1296707 TI - Analysis of protocol variations on DNA yield. AB - A modified alkaline lysis method for preparing plasmid DNA from bacterial cells has been developed for automation implementation. The objective of this study was to develop a simplified centrifuge-based protocol that can process samples in a microwell plate. These manual experiments and parametric studies show that the alkaline lysis method can be modified significantly to enable DNA preparations to be done rapidly and reliably by an automated system. The conclusions of this study were (a) centrifugation at < 1500 g is sufficient, (b) centrifugation times need not be extended to compensate for the reduced force, (c) reactions can be done at room temperature, (d) reagent volumes can be reduced over those typically used, and (e) certain reagents can be combined to simplify the handling of fluids. PMID- 1296708 TI - High-throughput DNA preparation system. AB - A system demonstrating the feasibility of high-throughput, centrifugation-based DNA separations and purifications has been constructed and tested. Samples are currently processed at a rate of 96 in approximately 2-3 h. The device implements an automation-optimized alkaline lysis protocol for the rapid extraction of plasmid or cosmid DNA from 1-ml bacteria cultures. The conditions for optimal culturing in deep-well (96 x 1 ml) microwell plates have been developed, and all sample manipulations are done within these plates. The use of microwell plates was essential to obtain high throughput and make manipulations following the DNA preparation (prep) easier because they can then be manipulated using a variety of commercially available robots. The entire prep system is constructed above a Beckman GPR centrifuge and operated under Macintosh IIcx control. This device has systems for fluid handling, microwell-plate manipulations, and centrifuge rotor alignment. PMID- 1296709 TI - Detection of single-base mutations in a mixed population of cells: a comparison of SSCP and direct sequencing. AB - Single-base-pair changes in several genes have been shown to be important in carcinogenesis. We have compared the sensitivity of two commonly used techniques for detection of single-base-pair changes. Defined populations of cells were prepared by mixing wild-type Chinese hamster ovary cells with cells carrying a known mutation in the CTP synthetase gene. RNA was extracted and analyzed for the mutation by single-strand conformational polymorphism and direct sequence analysis of polymerase chain reaction products. We found that both techniques were able to detect the mutation when it was present in 25% of the cells, but that direct sequencing was slightly more sensitive and able to detect the mutation when it was present in only 20% of the population. PMID- 1296710 TI - Histochemical techniques for locating Escherichia coli beta-galactosidase activity in transgenic organisms. AB - Escherichia coli beta-galactosidase is a commonly used reporter molecule for analyzing gene expression. Recently, beta-galactosidase fusions have been applied to a variety of eukaryotic systems. The techniques for constructing and introducing beta-galactosidase fusion constructs as well as soluble assays for total enzyme function have been described in detail elsewhere. This article describes histochemical techniques for analyzing organisms that contain a functional beta-galactosidase fusion construct. The object is to determine semiquantitatively which cells are expressing the beta-galactosidase fusion protein, as well as the subcellular localization of the protein. Due to its prevalence in the author's laboratory, Caenorhabditis elegans is used as a canonical organism for the detailed methods described. PMID- 1296711 TI - [Preliminary clinical trial of intrathecal rt-PA (TD-2061) for the prevention of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage]. AB - The results of preliminary clinical trial (a multicenter, open-label, dose escalation study) of intrathecal recombinant tissue plasminogen activator (rt-PA) for the prevention of cerebral vasospasm were reported. Seventeen patients admitted within 48 hours of subarachnoid hemorrhage (SAH) were enrolled in this study. Patients ranged from 42 to 69 years of age. All cases enrolled were classified in clinical grade II, III or IV according to the classification of Hunt and Kosnik and in group 3 or 4 according to Fisher's CT grading scale. Surgery for clipping the aneurysms were performed and a small silicone catheter was left in the subarachnoid space. Twenty four hours after the surgery intrathecal bolus infusion of rt-PA was started through the silicone catheter at 6-hour intervals for 3 days. Patients were divided into 4 groups based on the dosage of rt-PA for each infusion. The dosage of rt-PA for each infusion and a number of cases in each group was as follows; 25 KIU in 4 cases, 75 KIU in 6 cases, 200 KIU in 4 cases and 600 KIU in 3 cases. There was no significant difference in the clearance of subarachnoid clots between four groups. However, the occurrence of both symptomatic and angiographic vasospasm was less in the 75 KIU group than in other three groups. Intracranial bleeding complications were noted in 4 patients (1/6 in the 75 KIU group, 2/4 in the 200 KIU group and 1/3 in the 600 KIU group). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Disorientation was noted in 2 out of 3 patients of the 600 KIU group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296712 TI - [Correlation between clinical symptoms and draining pathways in dural arteriovenous malformation of the cavernous region]. AB - The clinical picture of dural arteriovenous malformations cannot be explained on the basis of degree of arteriovenous shunting in many cases. In this study, therefore we focused on the relation between clinical symptoms and draining pathways. Eighteen patients with dural arteriovenous malformation in cavernous region were studied before treatment. All patients underwent examination for their clinical symptoms, opthalmological examination and angiography on admission. Angiograms were used to determine the degree of arteriovenous shunting and the direction of draining pathway. The relationship between severity and shunt volume was inexplicable in many cases. However, close correlations appeared to exist between ocular hypertension and drainage pathways toward the orbit, between cranial nerve signs and drainage pathways toward the posterior fossa, and between headache and drainage pathways toward the cortical veins. PMID- 1296713 TI - [Effects of isosorbide dinitrate on regional cerebral blood flow and intracranial pressure in cats]. AB - The effects of isosorbide dinitrate (ISDN) on regional cerebral blood flow (rCBF) and intracranial pressure (ICP) were examined in cats. A low dose of ISDN (2.5 micrograms/kg/min) infusion did not show any changes in cerebral hemodynamics. During high dose of ISDN (5.0 micrograms/kg/min) or NTP (5.0 micrograms/kg/min) infusion, mean blood pressure (mBP) decreased by 10 to 20% accompanied by decreased cerebral perfusion pressure (CPP: mBP-ICP), however, rCBF or ICP did not change. It is concluded that intravenous administrations of ISDN in a dose of 2.5-5.0 micrograms/kg/min that produce slight decrease in blood pressure did not influence on cerebral hemodynamics. PMID- 1296714 TI - [A case of Meige's syndrome associated with post head trauma]. AB - The pathogenesis of Meige's syndrome (MS) is controversial and has yet to be determined up to today. We studied a case of MS associated with post head trauma. The patient was a 52-year-old female. At the age of 46, she began to suffer from oro-lingual dystonia after head trauma induced by a traffic accident and the brief administration of neuroleptics to the delusion deteriorated the dystonia. She showed a wry appearance after 1 year and 6 months of the trauma and began to exhibit blepharospasms, oro-mandibular dystonia and cervical dystonia after 2 years and 3 months. For these symptoms her daily life became difficult. These symptoms were resistant to various drug therapies, although trihexyphenidyl relieved the symptoms transiently. Laboratory examinations and cranial MRI findings were normal. By surface electromyogram of ocular orbicular muscles, bilateral continuous discharge was observed. This patient was diagnosed as MS by clinical symptoms and surface electromyogram findings. It was inferred that the head trauma was associated with the development of MS. We discussed the pathogenesis of MS in the present case and it was speculated that MS was presented by a minute lesion of the brain stem which was produced at the time of the head trauma. PMID- 1296715 TI - [Aspergillosis involving the thoracic spinal cord--an autopsy case]. AB - A 63 year old male complained of persistent backache and productive cough. The chest X-ray revealed the fungus ball at the left apical-posterior segment and Aspergillus fumigatus was cultured from the sputum. He was treated on fulconazole and miconazole. Six months later, motor and sensory paralysis below the mamillary level and urinary and stool incontinence developed. A magnetic resonance image disclosed the destruction of the second thoracic spinal vertebra involved by the cavitated fungus ball of the left lung. Continuous peroral administration of antifungal drugs was not successful, and he expired with severe dyspnea. The autopsy revealed an extensive granulomatous and purulent change of the epidural and subdural spaces of the second to fifth thoracic spinal cord. Subdural inflammation extended to the lower thoracic and lower cervical level. Thoracic spinal cord revealed an extensive myelomalacia predominantly involving the left lateral white column, and also anterior and posterior columns. Small areas of the white matter were cystic. The left anterior horn cells revealed severe central chromatolysis. Moderate lymphocytic and plasma cell infiltration was found around the vessels within the cord. A few thrombi were found in the vein near the anterior nerve root. Central nervous system involvement of pulmonary aspergillosis is quite uncommon. However, there are a few reports of patients with paraplegia secondary to the spinal extension by aspergillus infection. Sheth et al. described that epidural and subdural granulomatous change with aspergillus abscesses and spinal cord myelomalacia is comparable to metastatic carcinoma. However, the aspergillus infection in the spinal cord is more extensive and destructive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296716 TI - [Intracranial primary malignant lymphoma following Behcet's disease--case report]. AB - We reported a case of intracranial primary malignant lymphoma following Behcet disease treated with colchicine. A 43-year-old female with a past history of oral ulcer and folliculitis visited the Department of Ophthalmology on December, 1990, because of her impaired visual acuity. A diagnosis of uveitis due to incomplete type Behcet disease was made from funduscopic examination and her past history. She had been received 1.0mg/day colchicine for six months in the outpatient clinic. She was referred to our department on August 19, 1991, with nausea and headache. On admission, neurological examination revealed slight right cerebellar ataxia showing dysmetria and dysdiadochokinesis. Computed tomography scan and magnetic resonance images demonstrated a malignant lymphoma in the left cerebellar hemisphere. Stereotaxic biopsy resulted in the B cell type malignant lymphoma (Diffuse large cell type). Galliumscintigraphy, physical examination and peripheral blood examination disclosed no systemic abnormalities. There was a reduction of lymphocyte's response to PHA (phytohemagglutinin) stimulation (1.24). The tuberculin reaction was negative. Colchicine was discontinued and the therapy with radiation and prednisolone (20 mg/day) was started under the diagnosis of intracranial primary malignant lymphoma. She was discharged without any neurological deficits on November 25, 1991. She still suffers from impaired visual acuity, but has no problems in daily life. To our knowledge no intracranial primary malignant lymphoma following Behcet disease has been reported previously. The relationship between Behcet disease treated with colchicine and the occurrence of malignant lymphoma is discussed. In our case we speculated that malignant lymphoma might have occurred in an immunosuppressive state due to administration colchicine. PMID- 1296717 TI - [Epithelial cyst occurring on the anterior surface of the brain stem--case report and review of the literatures]. AB - Epithelial cysts in the posterior fossa are very rare, and only 22 cases have been reported in literatures. We report a case of epithelial cyst occurring on the anterior surface of the brain stem. A 31-year-old man was admitted to our hospital complaining of right hemiparesis and dysarthria. Plain CT showed a heterogeneous (isodense-hyperdense) mass in front of the pons, and was not enhanced after injection of contrast medium. As for findings of MRI, the tumor revealed as heterogeneous (isointense-hyperintense) mass on T1-weighted image and also heterogeneous (hypointense-hyperintense) mass on T2-weighted image. We removed partially the tumor which content was like yogurt. The histological findings of the cyst wall revealed a pseudostratified columnar ciliated epithelium. PMID- 1296719 TI - [Pathophysiology and treatment of reflex sympathetic dystrophy]. PMID- 1296718 TI - [A case of frontal lobe epilepsy presenting with recurrent speech arrest]. AB - We report a 55-year-old right-handed man with frontal lobe epilepsy manifesting recurrent speech arrest. He was known to have hypertension, hypertriglyceridemia, and gout. In the three days prior to admission, he had episodes of sudden inability to talk. These episodes lasted 10 to 30 seconds and recurred ten to twenty times a day. On admission, speech comprehension and other mental functions were normal, as were findings on neurologic examination. During the period of speech arrest, he understood spoken commands, and there was no abnormal motor activity or paresis. The episodes of speech arrest were thought to be short aphasic periods due to transient ischemic attacks in the left carotid territory. Computed tomography and magnetic resonance imaging demonstrated a small calcified lesion in the upper medial portion of the left frontal lobe. Left internal carotid angiography demonstrated no abnormal findings. After neuroradiological examination finished, he suddenly raised his right hand and followed it with his gaze and a right head turn. The EEG seizure pattern in which 20-25 Hz activity began in the left fronto-central region and spread rapidly to the right fronto central region, which after about 8 seconds was replaced by 12-14 Hz flattening rhythmic polyspikes was detected 9 times within 60 minutes. It is most unusual for supplementary motor area seizure to present pure paroxysmal speech arrest without accompanying paroxysmal motor activity. As in our case, epileptic arrest of speech may be confused with a transient ischemic attack of the dominant hemisphere. PMID- 1296720 TI - [Clinical utility and limitation of MRI in neuroradiology]. PMID- 1296721 TI - [High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy]. AB - We treated two patients with chronic inflammatory demyelinating polyneuropathy (CIDP) with high-dose intravenous immunoglobulin (HIG). The patients received 400 mg/kg of immunoglobulin a day for five days. One patient, who had failed to respond to prednisolone before, was treated with HIG, 18 months after the onset. His motor symptoms resolved immediately after the commencement of HIG. Electrophysiologically, the compound muscle action potentials increased in amplitude in all nerves examined and F wave reappeared in the left median nerve. The electrophysiological changes were compatible with improvement of conduction blocks. This patient had headache and exanthema during the HIG therapy, but they settled after cessation of the infusion. The other patient was administered HIG as an initial treatment, four months after the onset. HIG was of no effect in this case, but he showed remarkable recovery during the following prednisolone therapy. Although corticosteroid therapy is the first choice for CIDP, there are CIDP patients who do not respond to steroid or can not complete the steroid therapy because of adverse effects. HIG is an expectative and recommendable treatment for the steroid resistant CIDP patients. PMID- 1296722 TI - [Surgical treatment of brain stem lesions with reference to cavernous angioma]. AB - The surgical indications for localized brain stem lesions were evaluated retrospectively through the clinical results of 14 patients: 5 cavernous angiomas and 9 gliomas. Cavernous angiomas were located in fourth ventricle floor (2 cases), in dorsal midbrain (1 case), in right cerebellar peduncle (1 case), and in medulla oblongata (1 case). Those cases had direct surgery because of relapse of clinical symptoms and enlargement of the lesions on follow-up MR imagings. Each lesion was extirpated totally. Consequently, the majority of neurological deficits before operation improved. Therefore, radical extirpation in brain stem cavernous angioma was strongly recommended. Also, total, subtotal resection was performed for gliomas localized in brain stem: 2 low grade astrocytomas, 3 malignant astrocytomas, 3 plexus papillomas, and 1 ependymoma. Most of cases improved without new neurological deficits after surgery. In addition, MR imaging was considered to be essential to accurate diagnosis and surgical strategies for brain stem lesions. PMID- 1296723 TI - [Serotonergic mechanisms in hippocampal kindled seizures--inhibitory effects of L 5-hydroxytryptophan and 8-hydroxy-2-(di-n-propylamino)tetralin]. AB - Serotonin (5-HT) has been considered to possess an inhibitory action against the kindling development, but the role of 5-HT in kindled seizures is unclear. Furthermore, most previous studies have dealt with amygdaloid kindling. To clarify the role of the 5-HT system in epilepsy, we examined the effects of 5 hydroxytryptophan (5-HTP), a precursor which elevates brain 5-HT, and 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT 1 a receptor agonist, on seizures kindled from the feline hippocampus (HIP). Following the completion of HIP kindling, five cats received 0.9% saline, 5-HTP (20 or 40 mg/kg, i.p.) or 8-OH DPAT (0.1 or 1.0 mg/kg, i.v.). Drugs were administered 15 min (8-OH-DPAT) or 1 hr (5-HTP) prior to electrical stimulation at the generalized seizure triggering threshold, and the anticonvulsant effects were assessed by the behavioral seizure stage and afterdischarge (AD) duration. Both 5-HTP and 8-OH-DPAT suppressed dose dependently HIP-kindled seizures. The administration of 5-HTP at 40 mg/kg and of 8-OH-DPAT at 1.0 mg/kg produced a marked or complete suppression of HIP-kindled seizures in most of the cats tested, and was found to significantly reduce the seizure stage when compared with the saline control. Both drugs tended to shorten the AD duration, but this effect did not reach statistically significant levels. The present data suggest that the 5-HT system plays an important role in HIP kindled seizures, and that the 5-HT 1 a receptors have an inhibitory effect on the kindled focal epileptic activity of the HIP. PMID- 1296724 TI - [Local cerebral blood flow and its CO2 reactivity in the ischemic cerebrovascular diseases before and after bypass]. AB - We evaluated the effects of the STA-MCA anastomosis on local cerebral blood flow (LCBF) and CO2 cerebrovascular reactivity (CVR) in ischemic cerebrovascular diseases (CVD). [Patients and Methods] We examined the LCBF and CVR of 21 patients with ischemic CVD subjected standard STA-MCA anastomosis. During surgery, LCBF was continuously measured using the thermal diffusion method sometimes in a state of decreased PaCO2 (median: 7.2mmHg) before and after bypass. CVR was represented as % delta LCBF/delta CO2. [Results] 1) In the control group (with non-ruptured aneurysm, n = 7), LCBF was 58.6 +/- 14.1 ml/100g/min and % delta LCBF/delta CO2 was 4.68 +/- 1.68%/mmHg. 2) Before bypass, LCBF was 46.7 +/- 10.3ml/100g/min. It was significantly (p < 0.05) lower than control level. After bypass, LCBF increased significantly (p < 0.05) to 62.0 +/- 14.3 ml/100g/min. 3) Before bypass, % delta LCBF/delta CO2 was -1.36 +/- 4.34%/mmHg. In the 14 cases (66.7%), % delta LCBF/delta CO2 was below the 0%/mmHg (inverse steal effect). 4) After bypass, it increased to 0.08 +/- 2.73%/mmHg. 11 cases (52.4%) showed % delta LCBF/delta CO2 was above the 0%/mmHg. 5) In the group with a preoperative % delta LCBF/delta CO2 of less than 0%/mmHg, preoperative LCBF was 43.6 +/- 9.3 ml/100g/min, which was significantly low (p < 0.01) compared to that in the group with higher % delta LCBF/delta CO2. After bypass, LCBF and % delta LCBF/delta CO2 remarkably increased in the group with % delta LCBF/delta CO2 below 0%/mmHg. [Conclusion] Before bypass, LCBF was low and CVR was severely disturbed. In the 14 cases % delta LCBF/delta CO2 was below 0%/mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296725 TI - [Neurological disorders induced by antineoplastic drugs]. PMID- 1296726 TI - [Neurotoxicity of antiepileptic drugs]. PMID- 1296727 TI - [The analysis of nuclear organizer regions of astrocytomas with various histologic malignancies]. AB - Nucleolar organizer regions (NORs) correspond to the loops of DNA which encode the ribosomal RNA. Acid proteins related to NORs can be stained by the silver colloidal technique (AgNORs). Since the configurations of AgNORs may be related to the protein metabolism or the proliferative activity of the cell, we tried to evaluate the corelationship between the morphology of AgNOR and the histologic malignancy in astrocytic tumors. For the quantitative evaluation the histographic pattern of AgNORs was analysed. Twenty-seven surgical specimens of astrocytomas (astrocytoma; 7 Cases, anaplastic astrocytoma; 9 cases, glioblastoma; 11 cases) were examined. The average of the means of AgNOR count in astrocytoma, anaplastic astrocytoma, glioblastoma were 1.68, 1.85 and 2.76 respectively. The averages of standard deviations (S. D.) of AgNOR count were 0.87, 1.03 and 1.26, respectively. In those tumors, the AgNOR histograms were flattered and the means and S. D. increased significantly as the malignancy increased. We speculate that the increased number and variations of AgNOR count could be a reflection of phenotypic alterations of astrocytoma cells such as cellular anaplasia and pleomorphism. PMID- 1296728 TI - [Electrophysiological evaluation of human consciousness level by "Automated Fluctuation Analysis" of human high frequency EEG]. AB - This study is done to clarify the clinical meaning of "Automated Fluctuation Analysis" of high frequency EEG in man especially focused on the fine alteration of consciousness level of the subjects. Twenty normal volunteers were utilized for this study. They were divided into two groups, the subjects who felt sleepiness (Group S; N = 8) and the subjects who denied it (Group W; N = 12), during the EEG recording. "Automated Fluctuation Analysis" of high frequency EEG had been presented in our previous paper. In short, it is made of three steps, amplification of EEG signal, A/D conversion and Fast Fourier Transform by signal processor and extraction of Lorentzian parameters. Power spectral density (PSD) was displayed on log-log graph. Then the third step is performed by the best curve fitting program to the following equation, S (f) = S1/[1 + (f/fc1)2] + S2/ [1 + (f/fc2)2], where S(f) is power spectral density at any frequency f, S1 and S2 are plateau level of initial and second Lorentz, respectively and fc1 and fc2 are the corner or half power frequency of initial and second Lorentz, respectively. The algorithm of this program to extract these parameters were mathematically based on Brown & Dennis. As results, 1. PSD of human high frequency EEG was composed of double Lorentzians and vanished into white level within 1kHz. 2. A topographical display of S1 value revealed hyperfrontal in group W, which is in accordance with the cerebral blood flow study by Ingvar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296729 TI - [Nicergoline, an ergot alkaloid, improves ischemic brain damage by ameliorating the decreased cerebral blood flow and metabolism in spontaneously hypertensive rats]. AB - Effects of ergot alkaloids, nicergoline (NIC), on survival rate, brain water content, local cerebral blood flow (LCBF: 14C-iodoantipyrine) and glucose utilization (LCGU: 14C-2-deoxyglucose) were examined after bilateral carotid artery occlusion (BCAO) in spontaneously hypertensive rats. Two series of study were performed; the permanent BCAO and 3-hr-BCAO study. After permanent BCAO, the survival rate at 24 hrs of 32% (8 mg/kg, i.p.) or 38% (16mg/kg) in NIC group was higher than that in non-treated group (12%). At the end of 3-hr-BCAO, the increase in water content (dry-wet) in di-mesencephalon was less in NIC (100 micrograms/kg/min, i.v.) group than that in non-treated group. The decrease in LCBF in caudate-putamen (CP), parietal cortex (PC), thalamus (TH), hypothalamus (HT), and substantia nigra (SN) were less in NIC group than those in non-treated group. At the 2-hr-reperfusion after 3-hr-BCAO, the decrease in LCBF in TH and HT were less in NIC group than those in non-treated group. The LCGU in sensory motor cortex, CP, PC, HT, inferior colliculus and pons-reticular were higher in NIC group than those in non-treated group. From these results, it is concluded that nicergoline may have ameliorative effects on survival rate related to the prevention of decreased cerebral blood flow and metabolism following brain ischemia. PMID- 1296730 TI - [Changes in seizure-triggering threshold and after discharge duration in seizure susceptibility]. AB - Epilepsy is analysed on terms of two different conditions, seizure susceptibility and seizure induction. Reports on detailed changes of seizure-triggering threshold and after discharge duration in seizure susceptibility are few. We examined staged changes of seizure-triggering threshold and after discharge duration in seizure susceptibility in a cat amygdaloid kindling model. Ten crossed adult cats were used. We investigated after discharge threshold (ADT), partial seizure threshold (PST) in stage 4 group (P) and generalized seizure threshold (GST) in stage 6 group (C). At the same time, we examined after discharge duration on electroencephalograph (EEG) in each stage. Seizure triggering threshold decreases significantly step by step. After discharge duration increases significantly step by step. It is concluded that staged decrease of seizure-triggering threshold and increase of seizure's grade and duration was seen in seizure susceptibility. PMID- 1296732 TI - [Experimental syringomyelia in rabbits and rats after localized spinal arachnoiditis]. AB - In order to produce syringomyelia, localized arachnoiditis was created in adult New Zealand albino rabbits and Wistar rats by the injection of kaolin into the thoracic spinal subarachnoid space and incision of the dura mater of the thoracic spinal cord. The rabbits and rats were divided into 3 groups; the control group, dural incision group (DG) and kaolin injection group (KG). Each rabbit was sacrificed at 4, 8, 12 and 16 weeks after the operation. Each rat was sacrificed at 8 and 16 weeks after the operation. Cavity formation in the cord of all rabbits was examined by ultrasound. All animals were perfused with 10% neutral beffered formalin at 150 cm H2O pressure, and histological examination was performed with Luxol fast blue (LFB) and hematoxylin and eosin (H&E) stains. Results obtained: (1) Cavity formation was noted in 6 of 16 DG of rabbit (37.5%), 5 of 16 KG of rabbit (31.2%) and 2 of 9 KG of rat (22.2%) with histological verification. With use of ultrasound, cavity was noted in 3 of 16 DG rabbits (12.5%) and 2 of 16 KG rabbits (18.8%). (2) Cavity formation was present in the cord adjacent to the marked adhesive arachnoiditis both in rabbits and in rats. (3) Cavity was noted in the ischemic area. (4) In 2 rabbits in which kaolin encircled whole surface of the spinal cord, hydromyelia was formed communicating with enlarged central canal caudad from the kaolin subarachnoid block. (5) Histological examination showed obliteration or narrowing of lumen of the small pial vessels involved in the adhesive arachnoiditis. In the cord parenchyma adjacent to the arachnoiditis, multiple spots of demyelination due secondary to ischemia demonstrated by LFB stain were noted. On the other hand, in the cord with the pia-arachnoid remained uninvolved, no demyelination was observed. (6) Localized adhesive arachnoiditis consisted of proliferation of fibrous tissue, lymphocytic infiltration and obliterating processes of small pial vessels involved in it. These data suggest that the cavitation within the cord would be induced by the ischemia, and hydromyelia would be produced by the pressure dissociation between the spinal subarachnoid space and the central canal. PMID- 1296731 TI - [Application of immunohistochemistry to the dead brain]. AB - To evaluate the usefulness of immunohistochemistry for studies of brain tissues taken from patients with a clinically established diagnosis of brain death, we examined 8 brains that had been removed and fixed in formalin between 13 h and 5 days after diagnosis of brain death (Table). As a control we also examined the brain of a patient who had suffered extensive infarction with a 28-day clinical course and died of pneumonia. Routine examination of each of the brains revealed old to recent tissue necrosis associated with macrophages, capillary proliferation and/or astrocytic gliosis. The streptavidin-biotin immunoperoxidase method was applied to the materials using four monoclonal antibodies: antiglial fibrillary acidic protein (GFAP), anti-vimentin (vimentin), LN-1 and LN-3. GFAP was stained in reactive astrocytes even 5 days after diagnosis of brain death (Fig. 3, 7). Vimentin (Fig. 2, 4) was stained in reactive astrocytes until 3 days after diagnosis of brain death. LN-1 (Fig. 5) produced positive staining in resting microglias until 3 days after diagnosis of brain death. LN-3 (Fig. 1, 6, 8), which detects human leukocyte antigen-DR, stained reactive microglias and macrophages even 5 days after diagnosis of brain death. From our findings, it is considered that immunohistochemical examination is useful even in brains from patients diagnosed as brain-dead. PMID- 1296733 TI - [Surgical outcome of 32 cases in traumatic subdural hygroma]. AB - 32 cases of traumatic subdural hygroma (TSH) in adults with surgical treatment were retrospectively investigated by means by clinical features and CT findings. The cases consisted of 29 males and 3 females, aged 41 to 87 years (mean 69). Preparative CT scan of all cases revealed low density area and crescent shape in frontotemporal or frontoparietal subdural space. Half of the cases had bilateral lesions. At operation of TSH, color of subdural fluid collections was more water clear or xanthochromic than bloody. As a results, 22 out of 32 cases (69%) in TSH improved with surgical treatment. Many of effective cases of surgical treatment in TSH had short interval from trauma to operation and light disturbance of consciousness before operation. However, the other intracranial damage will also affect the clinical outcome of TSH, because the majority of cases in this study was accompanied by an intracranial damage including cerebral contusion, subarachnoid hemorrhage or intracranial hemorrhage. Nevertheless, surgical management for TSH was so effective that the operation should be undergone sooner interval from trauma, simultaneously considering the another intracranial lesions except TSH. But then, we experienced 7 cases (22%) of ventricular dilatation and 5 cases (16%) of chronic subdural hematoma in postoperative follow up CT scans. In 5 cases among the former, ventriculoperitonial shunt was done, and in 3 cases among the latter, burr hole evacuation was performed. Therefore, the postoperative course of TSH should require careful observation by CT scan and so on. PMID- 1296734 TI - [A case of aneurysm of the peripheral middle cerebral artery presenting putaminal hemorrhage--pitfall in diagnosis]. AB - A case mimicking hypertensive putaminal hemorrhage which was first treated by CT guided stereotactic aspiration and eventually diagnosed as a sequence of the ruptured aneurysm of the left peripheral middle cerebral artery on postoperative angiography is presented. This 41 old, right-handed, hypertensive female suffered sudden onset of headache and right hemiparesis. Next day hematoma was evacuated by the CT-guided stereotactic aspiration because of progressive deterioration of the consciousness and patient recovered well. Fourteen days after the evacuation when she presented mild right hand weakness and motor aphasia, angiography revealed a saccular aneurysm with broad neck derived from left posterior parietal artery. A neck clipping necessitated an additional anastomosis between superficial temporal artery and distal middle cerebral artery because of parent artery stenosis. Postoperatively she is doing well with slight motor aphasia. Among the typical hypertensive putaminal hemorrhage diagnosed on CT scan, it is stressed that there may be a possibility of ruptured aneurysm situated on the peripheral middle cerebral artery. PMID- 1296735 TI - [Community health physicians in Troms: home care aides not qualified to nurse]. PMID- 1296736 TI - [Flexitime in a hospital ward]. PMID- 1296737 TI - [Restructuring can lead to unrest. Interview by Siv Barstad]. PMID- 1296738 TI - [Unrest increases]. PMID- 1296739 TI - [Nursing under a different sky--Kabul]. PMID- 1296740 TI - [Unrest as a phenomenon]. PMID- 1296741 TI - [Asia: AIDS--a threat against the country's economy]. PMID- 1296742 TI - [With support from Norwegian nurses: midwifery education in Bethlehem]. PMID- 1296743 TI - [With support from Norwegian nurses: independent midwives]. PMID- 1296744 TI - [Norwegian nurses' international involvement]. PMID- 1296746 TI - [So many possibilities and big challenges. Interview by Bjorn Arild Ostby]. PMID- 1296745 TI - [Like a bird--Phoenix rising from the ashes]. PMID- 1296748 TI - [Started her 2d career when she reached retirement age. Interview by Kjell Arne Bakke]. PMID- 1296747 TI - [Bureaucrat with open door. Interview by Siv Barstad]. PMID- 1296750 TI - [Unlawful management of home nursing. "Regulations can be interpreted". Interview by Kjell Arne Bakke]. PMID- 1296749 TI - [Unlawful management of home nursing. 31 communities violate law. Interview by Kjell Arne Bakke]. PMID- 1296751 TI - [Unlawful management of home nursing. Nursing in the home must have the same quality as in the hospital. Interview by Bjorn Arild Ostby]. PMID- 1296752 TI - Novel structural patterns in divalent cation-depleted surface layers of Aeromonas salmonicida. AB - The fish pathogen Aeromonas salmonicida possesses a regular surface layer (or A layer) which is an important virulence determinant. The A-protein, a single bilobed protein organized in a p4 lattice of M4C4 arrangement with two morphological domains, comprises this layer. The role of divalent cations in the A-layer structure was studied to better understand A-protein subunit interactions affecting structural flexibility and function. Divalent cation bridges were found to be involved in the integrity of the A-layer. Two novel A-layer patterns were formed as the result of growth under calcium limitation or by chelation of divalent cations with EDTA or EGTA, thereby constituting the first reported case of formation of distinct regular arrays upon divalent cation depletion. Furthermore, under these conditions A-protein was sometimes released as tetrameric units, rather than in monomeric form. The formation of the two novel patterns is best explained by a sequence of structural rearrangements, following disruption of only one of the two A-layer morphological units, that is, those held together by divalent cation bridges. The free tetrameric units represent four A-protein subunits clustered around the unaffected four-fold axis. PMID- 1296753 TI - Ultrastructural evidence for a triple structure of the lateral element of the synaptonemal complex. AB - This study describes composition and localization of several substructures of the synaptonemal complex (SC) using different techniques. The techniques which were used were surface spreading, critical point drying of isolated SCs, and sectioning of Lowicryl embedded testis material. The lateral elements (LEs) of the SC appear to be composed of three lateral substructures: two morphologically identical major strands and a third strand which is considerably thinner. The thinner strand is localized on the inner side of the two major strands of the lateral element. In late pachytene/early diplotene stages when the SC starts to disintegrate more than three strands can be observed in the LEs. A model is presented and the function of the different substructures is speculated upon. PMID- 1296754 TI - Biochemical and ultrastructural studies of the C-type lectin bovine conglutinin. AB - The aim of this study was to correlate the supramolecular organization of conglutinin (BK) with its primary and tertiary structure and to gain more knowledge of functionally important regions of the molecule. BK analyzed by SDS PAGE under standard reducing conditions (40 mM DTT) showed a major band at 43 kDa and weaker bands at 86 and 180 kDa. In contrast, reduction with 6-50 mM L cysteine resulted in 37-kDa subunits indicating the presence of intrachain disulfide bonds within this subunit. Hydroxylamine treatment indicated presence of ester bonds in the 86- and 180-kDa subunits. Collagenase digestion and SDS PAGE under reducing and nonreducing conditions resulted in bands of 20 and 15 kDa, respectively, indicating the presence of intrachain, rather than interchain, disulfide bonds in the carboxy terminus. Deglycosylation and glycan differentiation analysis of BK revealed the presence of O-linked glycans of GalNAc and alpha (2-3) linked sialic acid type, whereas no N-linked glycans were demonstrated. Binding experiments with GlcNAc-gold suggested that multivalency is required for carbohydrate binding to BK. Electron microscopy showed mostly tetramers, 96 nm in diameter, but also mono-, di-, and trimers were seen. The tetramers consisted of 40-nm strands, each with a peripheral globular head composed of subunits and connected to a common central lobe built from four ring formed structures. The strands occasionally showed two bends, one close to the central lobe and another 25 nm from the lobe. These bends most likely correspond to the interrupted Gly-Xaa-Yaa repeats at residues 38 and 123. PMID- 1296755 TI - MgATP binding changes neither the shape nor the flexibility of the heads of single myosin molecules. AB - The structural mechanism by which myosin heads exert force is unknown. One possibility is that the tight binding of the heads to actin drives them into a force-generating configuration. Another possibility is that the force-generating conformational change is inherent to the myosin heads. In this case the heads would make force by changing their shape according to the species of nucleotide in their active sites, the tight attachment to actin serving only to provide traction. To test this latter possibility, we used negative stain electron microscopy to search for a MgATP-induced shape change in the heads of single myosin molecules. We compared the heads of 10S smooth muscle myosin monomers (wherein MgATP is trapped at the active site) with the MgATP-free heads of 6S monomers. We found that to a resolution of about 2 nm, MgATP binding to the unrestrained myosin head does not drive it to change its shape or its flexibility. This result suggests that the head makes force by virtue of an induced fit to actin. PMID- 1296756 TI - Polarity of microtubular structures in manchette-like formations: possible role of the "11th filament". AB - Bundles of microtubular structures appear in the cytoplasm of spermatids of the African frog Dicroglossus occipitalis. They are observed in the vicinity of axonemes. Natural tubulin polymerization leads to the formation of hooks on microtubular structures. They can be related to experimentally induced tubulin hooks. The direction of curvature of the hooks allows us to define the polarity of the bundles. This is opposite to the polarity of axonemal microtubules: Bundles and axonemes are antiparallel. Under colchicine action, arch-like microtubular structures are shown to open in the same direction as they lock. This enables us to characterize their opening and locking site: It corresponds to the place of the "11th filament" described in microtubular structures such axonemes. The "11th filament" is thus demonstrated to be the most susceptible to natural opening and to the action of colchicine in microtubular structures. PMID- 1296757 TI - Assembly of 2-D membrane protein crystals: dynamics, crystal order, and fidelity of structure analysis by electron microscopy. AB - Membrane protein reconstitution into two-dimensional (2-D) ordered arrays is described. The assembly of 2-D crystals may be modeled as a two-step process: the membrane protein is first integrated in the lipid bilayer and then crystallized by removal of excess detergent or lipid and/or by precipitating agents. Lipid detergent, protein-detergent, and lipid-protein interactions are critical during the first step, while lipid-protein and protein-protein interactions dominate events in the second step. The evidence supporting this model results from quasielastic light scattering analyses and electron microscopy of different lipid detergent systems and reconstitution experiments with Escherichia coli porin OmpF, Phormidium laminosum photosystem I reaction centers, and integral membrane proteins of mammalian lens fiber cells. PMID- 1296759 TI - Decreased uptake of low density lipoprotein by LLC-PK cells cultured at low magnesium concentration. AB - LLC-PK cells grown in tissue culture on medium containing normal or deficient amounts of magnesium were presented with 125I-low density lipoprotein (LDL) and the uptake determined. Total LDL uptake by Mg-deficient cells decreased as the magnesium concentration decreased. The receptor binding of LDL and the internalization of LDL by the Mg-deficient cells were reduced. Degradation of LDL by Mg-deficient cells, when corrected for the reduced uptake, was less affected. PMID- 1296758 TI - Actin crosslinking protein EF-1a of Dictyostelium discoideum has a unique bonding rule that allows square-packed bundles. AB - The elongation factor 1a (EF-1a) of Dictyostelium discoideum is an actin crosslinking protein that gives rise to a unique kind of actin bundle. Purified actin and EF-1a were allowed to form bundles and then were characterized by electron microscopy, computed diffraction analysis, and modeling. In these bundles crosslinked actin filaments are rotated by 90 degrees relative to each other, whereas other known crosslinking proteins require filaments to be unrotated. Bundles of actin EF-1a would tend to exclude other actin bundling proteins. EF-1a can thus regulate the state of the actin cytoskeleton as well as regulate protein synthesis. PMID- 1296760 TI - Influence of endothelium in the in vitro vasorelaxant effect of magnesium on aortic basal tension in DOCA-salt hypertensive rat. AB - The objective of this study was to examine the influence of the endothelium on the extracellular magnesium induced relaxation of basal tension in isolated aortas from both mineralocorticoid-salt (DOCA-salt) hypertensive and control normotensive Sprague Dawley male rats. After incubation in magnesium-free physiological salt solution (PSS) (O mM magnesium), the increase of extracellular magnesium (1.2; 4.8 mM magnesium) caused a decrease in aortic tone which was significantly greater when endothelium was disrupted. Magnesium-induced relaxation was also more pronounced when endothelial NO production was blocked by 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME). It is suggested that the vasorelaxation induced by extracellular magnesium is linked to the level of aortic basal tension developed in magnesium-free PSS. The endothelium does not seem to be directly implicated in magnesium-induced vasorelaxation in aortas from normotensive rats. However, in DOCA-salt hypertensive rats, the magnesium-induced relaxation of basal tension was less in the intact aorta (though not when the endothelium was disrupted) when the cyclo-oxygenase pathway was blocked by 10(-6) M indomethacin. These data therefore suggest that extracellular magnesium can promote relaxation by endothelium-dependent and cyclo-oxygenase-dependent mechanisms such as the production of relaxing prostacyclin in isolated aorta from DOCA-salt hypertensive rats. PMID- 1296761 TI - Spectral analysis of electroencephalography data in athletes with low erythrocyte magnesium. AB - In a population of high level athletes (kayakists) we compared quantitative electroencephalography data in those with low erythrocyte (magnesium magnesium deficit) and those with normal magnesium (controls). Logistic regression showed that the relative power of the alpha frequency band in the occipital lead is the most discriminant (P < 0.05). There was a significant positive correlation between low erythrocyte magnesium and alpha relative power (P < 0.05). An alteration of magnesium homeostasis could explain the occurrence of magnesium deficiency in athletes. PMID- 1296762 TI - New data on the antiarrhythmic value of parenteral magnesium treatment: magnesium and ventricular arrhythmias. AB - Antiarrhythmic magnesium (Mg) therapy was evaluated in 20 normomagnesaemic patients affected by ischaemic dilated cardiomyopathy (ID) and severe ventricular arrhythmias, and in 10 patients with torsade de pointes (TdP) occurring in the setting of acquired QT interval prolongation. In the group with IDC, magnesium sulphate was given as slow infusions (50 mg/min over 60 min) twice a day for 7 d. This was antiarrhythmic in all of the patients: ventricular premature contractions and couplets decreased from 13,979 +/- 8964 (mean +/- SD) to 382 +/- 265 (P < 0.001), and from 516 +/- 274 to 9 +/- 6 (P < 0.001), respectively; runs of ventricular tachycardia (41.9 +/- 14.2) disappeared by the fifth day of treatment. The efficacy of antiarrhythmic treatment was evaluated by 24 h Holter monitoring obtained in baseline conditions and after 3, 5 and 10 d from beginning of therapy. In patients with TdP, Mg infusions were instituted at a slow rate (50 mg/min) and continued for 2 h after disappearance of Tdp, which occurred within 20 to 30 min from the start of the Mg infusions. These were followed by prophylactic infusions at rate of 30 mg/min for 90 min twice a day over the next 3 to 4 d. No side effects were observed, and heart rate and QTc remained unchanged from baseline values. In conclusion, Mg infusions may be an effective antiarrhythmic treatment for short and medium-term control of severe ventricular arrhythmias associated with IDC, and may prove useful in the acute treatment of TdP, especially in situations where conventional therapy might prove deleterious or difficult. PMID- 1296764 TI - Influence of the magnesium content of drinking water and of magnesium therapy on the occurrence of preeclampsia. AB - A reverse relationship was found between the magnesium content of drinking water, ie. an adequate supply of highly available dietary magnesium, and the occurrence of preeclampsia. Where various parts of a settlement receive their drinking water from different sources (for example, surface water or well water) there may be an important difference in the level of magnesium supply to different population groups. In the population studied here, the occurrence of preeclampsia varied pari passu with the magnesium content of the drinking water in different parts of the city. The results show that during pregnancy the magnesium content of serum and erythrocytes decreases. This decrease may be prevented by magnesium therapy, which lowers the incidence of preeclampsia. PMID- 1296763 TI - Effects of increased dietary phosphorus on magnesium balance in very low birthweight babies. AB - The effects of three dietary phosphorus concentrations on magnesium balance in very low birth weight (VLBW) infants were measured. The infants consumed one of three special formulas for 20 consecutive days. Magnesium balance was calculated by measuring food intake, urinary magnesium and fecal magnesium. The highest dietary phosphorus concentration resulted in a higher (P < 0.05) fecal loss of magnesium. Net absorption and net retention of magnesium were lower (P < 0.10) in the high phosphorus group. A modest (33 per cent) increase in dietary phosphorus resulted in a decrease in magnesium absorption in VLBW infants. PMID- 1296765 TI - Magnesium and immune function: recent findings. AB - Recent findings regarding roles for magnesium in immunocompetence confirm and extend previous knowledge of its participation in natural and adaptive immunity. The detrimental effects of severe magnesium deficiency have been confirmed. There is better comprehension of how magnesium relates to mechanisms that control cellular activities and regulate interactions among cells that affect immune functions. Insight has been gained into how magnesium status affects susceptibility to physiological disorders, such as cardiomyopathy and cancer, that are exacerbated by inflammation and by the chemical mediators of anaphylaxis. More information is needed about the impact of less severe magnesium deficiency and of supplemental magnesium on indicators of immune function. Future studies should explore interactive relationships between Mg and such nutrients as vitamin D to elucidate more completely the roles that Mg can play in optimizing immune function. PMID- 1296766 TI - Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis. AB - The proposed aetiologies of multiple sclerosis (MS) have included immunological mechanisms, genetic factors, virus infection and direct or indirect action of minerals and/or metals. The processes of these aetiologies have implicated magnesium. Magnesium and zinc have been shown to be decreased in central nervous system (CNS) tissues of MS patients, especially tissues such as white matter where pathological changes have been observed. The calcium content of white matter has also been found to be decreased in MS patients. The interactions of minerals and/or metals such as calcium, magnesium, aluminium and zinc have also been evaluated in CNS tissues of experimental animal models. These data suggest that these elements are regulated by pooling of minerals and/or metals in bones. Biological actions of magnesium may affect the maintenance and function of nerve cells as well as the proliferation and synthesis of lymphocytes. A magnesium deficit may induce dysfunction of nerve cells or lymphocytes directly and/or indirectly, and thus magnesium depletion may be implicated in the aetiology of MS. The action of zinc helps to prevent virus infection, and zinc deficiency in CNS tissues of MS patients may also be relevant to its aetiology. Magnesium interacts with other minerals and/or metals such as calcium, zinc and aluminium in biological systems, affecting the immune system and influencing the content of these elements in CNS tissues. Because of these interactions, a magnesium deficit could also be a risk factor in the aetiology of MS. PMID- 1296767 TI - Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. AB - Magnesium is an essential cofactor for many enzymatic reactions, especially those involved in energy metabolism. Deficits of magnesium are prevalent due to inadequate intake or malabsorption and due to the renal loss of magnesium that occurs in certain disease states (alcoholism, diabetes) and with drug therapy (diuretics, aminoglycosides, cisplatin, digoxin, cyclosporin, amphotericin B). Protracted deficits of magnesium in humans and animals result in neurological disturbances, including hyperexcitability, convulsions and various psychiatric symptoms ranging from apathy to psychosis, some of which can be reversed with magnesium supplementation, others requiring correction of the dysregulation mechanism. Although the role of magnesium in neuronal function is not completely understood, a lowering of CSF or brain magnesium can induce epileptiform activity and there is an association between decreased CSF magnesium and the development of seizures. CSF concentrations of magnesium are normally higher than magnesium plasma ultrafiltrate (diffusible) concentrations due to the active transport of magnesium across the blood-brain barrier. Under conditions of magnesium deficiency, CSF concentrations decline, although this decline lags behind and is less pronounced than the changes observed in plasma magnesium concentrations. Decreases in CSF magnesium concentrations correlate with the alterations observed in extracellular brain magnesium concentrations in animals following the dietary deprivation of magnesium. CSF magnesium concentrations can readily be repleted following magnesium supplementation, although high dose magnesium therapy, such as that used in the treatment of convulsions in eclampsia, will only increase CSF magnesium concentrations to a very limited degree (approximately 11-18 per cent) above physiological concentrations. Greater increases in CSF magnesium may occur in neonates since neonatal swine, following treatment with magnesium, have CSF magnesium concentrations that are similar to their plasma concentrations. There has been a recent resurgence of interest in magnesium deficiency and its neurological consequences due to the finding that magnesium, at physiological concentrations, blocks N-methyl-D-aspartate (NMDA) receptors in neurones. NMDA receptors are normally activated by glutamate and/or aspartate which represent the principal neurotransmitters for excitatory synaptic transmission in vertebrate CNS. Magnesium deficiency produces epileptiform activity in the CNS which can be blocked by NMDA receptor antagonists. Other mechanisms, including alterations in Na+/K(+)-ATPase activity, cAMP/cGMP concentrations and calcium currents in pre- and postsynaptic membranes, may also be at least partially responsible for the neuronal effects associated with low brain magnesium. Further studies are necessary to increase our understanding of the neurological implications of magnesium deficit in the central nervous system. PMID- 1296768 TI - Commentary on recent clinical advances: almonds, monounsaturated fats, magnesium and hypolipidaemic diets. PMID- 1296769 TI - Bone marrow imaging in plasma cell dyscrasias: review of 130 cases. AB - Skeletal radiography, bone and bone marrow scintigraphy have been performed in 130 patients with plasma cell dyscrasias (119 multiple myeloma, 9 MGUS and 2 Waldenstrom disease). Our results confirm: 1) that radiography is much more sensitive than scintigraphy in the identification of the lesions typical of myeloma, but in the first stage bone scintigraphy and especially bone marrow scintigraphy are more sensitive than x-ray for the detection of regions affected by focal lesions; 2) that bone scintigraphy is of particular value in detecting some abnormalities in specific sites not fully visualized by x-ray; 3) that bone marrow scintigraphy is a valuable diagnostic tool in the early stage of myeloma, especially for evaluating the progression of the disease, because it is able to demonstrate not only focal lesions, but also bone marrow expansion. We believe that bone marrow scintigraphy may be a useful technique in the early diagnosis and follow-up of multiple myeloma, particularly in the detection of unusual forms (i.e., "smouldering" myeloma), but it remains only an "additional" technique for bone imaging. PMID- 1296770 TI - Evaluation by captopril renal scintigraphy and echo-Doppler flowmetry of hypertensive patients at high risk for renal artery stenosis. AB - Sixty-three hypertensive patients with probability of obstructive renal artery disease underwent both Captopril renal scintigraphy (CRS) and echo-Doppler flowmetry (EDF) before undergoing renal angiography. Angiography revealed renal artery stenosis (RAS) in 42 patients (unilaterally in 26 and bilaterally in 16). The sensitivity and specificity in the identification of RAS > or = 50% were 90% and 94%, respectively for Captopril renography, and 85% and 78% for echo-Doppler flowmetry. Captopril renography correctly identified stenoses greater than 50%, which is usually held to be the limit of hemodynamic significance. While the Doppler examination was more sensitive than Captopril renography (sensitivity 79% versus 64%) in the detection of all degrees of RAS, less information on the functional significance of RAS was provided. Both CRS and EDF could be usefully employed to assess kidney perfusion, but their appropriate clinical use must take into account inherent differences between the two techniques. PMID- 1296771 TI - Quantitative evaluation of 99mTc-hexamethylpropylenamineoxime brain SPECT in childhood-onset epilepsy. AB - In 10 patients with childhood-onset epilepsy, quantitative evaluation (QE) of interictal regional cerebral blood flow (rCBF) using technetium-99m hexamethylpropylenamine oxime (99mTc HMPAO) single-photon emission computed tomography (SPECT) was correlated with seizure foci localized by electroencephalography (EEG). Eighty regions of interest (5 x 5 pixels) were placed at five different neocortical areas in both cerebral hemispheres, in coronal and transaxial planes. Mean counts/pixel were calculated for each region and multiple right-left comparisons were done. Quantitative evaluation of 99mTc HMPAO increased detection of rCBF abnormalities by 26%. Abnormal EEG patterns correlated with abnormal rCBF in 75% of cases (Phi = 0.788, p < 0.001), and with visually detected abnormalities in 50% (Phi = 0.493, p < 0.001). Discordance between EEG and SPECT was most frequent in patients with non-localizing EEG (n = 3). In childhood-onset epilepsy, quantitative evaluation of brain perfusion scans provides: (a) objective estimates of interictal rCBF; (b) more precise detection of epileptogenic foci, when used to complement EEG. PMID- 1296772 TI - PET studies of cognitive functions: a review. PMID- 1296773 TI - Future scenarios for nuclear medicine. PMID- 1296774 TI - 67Ga-citrate imaging in rhabdomyosarcoma. AB - A 22-year-old female patient with a swelling in the right forearm near the elbow underwent a 67Ga-citrate scan because of paraesthesia on the ulnar side of the right hand. The 67Ga total body scan showed intense focal uptake on the forearm in the same position as the swelling. At surgery a histological diagnosis of alveolar rhabdomyosarcoma was made. Five months later, a repeat 67Ga scan was normal. Eight months after the diagnosis, the patient complained of pain in the left lumbar region extending to the hypogastric area. A third 67Ga scan showed intense uptake near the spinal column which at surgery was found to be a metastasis of the primary tumor. PMID- 1296776 TI - [Chronic hepatitis B infection in childhood: the possible therapeutic interventions]. PMID- 1296775 TI - [Chronic hepatitis: a chapter to be rewritten?]. PMID- 1296777 TI - [The transcatheter recanalization of occluded portosystemic shunts]. AB - The authors present their personal experience in percutaneous treatment of portosystemic shunt occlusion and stenosis by percutaneous transluminal angioplasty (PTA) and fibrinolytic local infusion. Twelve patients with portosystemic shunt stenosis or occlusion were percutaneously treated. In 8 patients only PTA was performed, 4 were treated with local fibrinolytic infusion, in 3 of the latter cases this treatment was followed by PTA. In all 12 patients recanalization was successful and non complications arose. Six patients died in the following 15 months, none due to rebleeding. In 5 of these patients the shunt was patent at post-mortem examination. In the 6 patients still alive in the follow-up period (2 to 25 months, mean 14.5 months) the shunt was patent in 4 and occluded in 2. IN CONCLUSION: percutaneous treatment with PTA or fibrinolytic local infusion is preferable in non-functioning portosystemic shunt; further surgery is always extremely risky in such patients. PMID- 1296778 TI - [The clinical importance of physiopathological studies of the bile salts performed using the gamma-emitting bile acid SeHCAT]. AB - The availability of the gamma-labelled bile acid 75SeHCAT, that allows a non invasive assessment of the enterohepatic circulation of bile acids, has prompted in the last 10 years the implementation of several studies involving wide series of normal subjects and patients with various organic and functional bowel disorders. The clinical indications for performing a SeHCAT test have been clearly defined: the test can identify with high accuracy, in the setting of the irritable bowel syndrome, the patients with bile acid malabsorption that can be confidently and successfully treated with cholestyramine; it can also assess whether, and to what extent, the diarrhoea presenting in patients with intestinal organic disorders is due to bile acid malabsorption, permitting an optimal therapeutic strategy to be designed. The parameters of the hepatic handling of SeHCAT after bolus intravenous administration have been characterized in normals, and studies on various chronic hepatic disorders are now in progress. Interesting results are emerging from studies performed in patients with chronic non obstructive cholestatic disease, where a specific defect in the excretion rate of SeHCAT is present: these studies may cast more light on the abnormalities of bile secretion and on the mechanism of action of drugs used to treat this condition, forming the rationale for the use of intravenous SeHCAT for hepatobiliary dynamic scintigraphy as a sophisticated liver function test. In conclusion, the SeHCAT test has become an important diagnostic tool for the gastroenterologist studying the diarrhoea, and awaits more studies to be used also by the hepatologist. The relatively long physical half-life of 75Se (180 days), preventing a wider use of the test, could theoretically be overcome by the synthesis of a similar gamma labelled bile acid with a shorter half-life. PMID- 1296779 TI - [Ileal adenocarcinoma in Crohn's disease. A report of 2 cases]. AB - The incidence of intestinal adenocarcinoma in Crohn's ileal disease is reported in the literature to be higher than in the normal population. The authors report two cases of adenocarcinoma observed during the course of Crohn's ileitis and, by comparing these findings with earlier published data, highlight their characteristics. Two patients, a 53-year-old woman and a 62-year-old man, are reported as suffering from Crohn's ileitis. The woman underwent resection of the right colon with ileo-transversostomy due to stenosis twenty years earlier, whereas diagnosis in the male patient dates back to an appendicectomy 11 years earlier. Surgery, which was performed in both due to subocclusion which failed to respond to steroid therapy, showed the typical alterations of Crohn's disease. An adenocarcinoma was also found in both patients in the stenotic zone with highly dysplasic foci. The man presented a monoclonal gammopathy of an IgA-type with light lambda chains and Bence-Jones' proteinuria. Both patients are living and enjoy apparently good health respectively 2 and 6 years after surgery. The authors emphasize that the association between Crohn's ileal disease and intestinal adenocarcinoma cannot be considered casual. In the literature the relative risk is reported to be between 6 and 320 times higher, with approximately 1 out of 350 patients suffering from both diseases contemporaneously. In the series reported earlier, 2 cases of carcinoma were diagnosed in 38 Crohn's patients studied over a period of 12 years out of a total population of 114000 inhabitants, with a frequency of carcinoma of 5.13% compared to 0.3% reported in the literature. The incidence of Crohn's disease was 2.84/100000 per year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296780 TI - Grim prospects for the unemployed. PMID- 1296781 TI - Diabetes in aborigines and other Australian populations. AB - The aetiology of diabetes mellitus is reviewed in the light of Australian epidemiological studies. The prevalence of diabetes has been studied in a wide variety of Australian settings. Comparisons of prevalences in Aborigines and other populations suggest that occurrence of this disease has both genetic and environmental determinants. Diet and obesity are associated with diabetes, but to increase physical exercise may be the most feasible intervention. Public health approaches are discussed. PMID- 1296782 TI - Future directions for mental health services in Australia. AB - The last decade has seen a marked increase in the attention given to mental health policy and services at both a state and national level. Mental health consumers, carers, service providers, and a number of professional bodies have contributed to the scrutiny of what had been a relatively neglected area. The release of Australia's first National Mental Health Policy is a milestone in the development of a national focus on mental health promotion, prevention and the provision of enhanced services for persons with mental disorder and mental health problems. This paper discusses briefly the directions promoted in the national policy, including mental health promotion, reorientation of mental health services, the nongovernment sector, consumer rights, intersectoral links, service quality, research and evaluation. PMID- 1296783 TI - Availability of cigarettes to minors. AB - Legislation banning the sale of cigarettes to minors is potentially a cost effective means of reducing smoking rates among adolescents. Such legislation has been in existence in Australia for over 80 years. Two studies examined the retail industry's adherence to the sales ban in two regions of New South Wales in 1990. The first study was a survey of 1,849 12- to 15-year-old adolescents from 12 high schools in New South Wales, providing data on self-reported purchasing of cigarettes from retail outlets by minors. In all, 38 per cent reported having purchased cigarettes illegally. A second study was undertaken to determine the proportion of retail shops which sell cigarettes to apparently underage youth. Two 16-year-olds who looked young for their age attempted to purchase cigarettes from 101 different retail outlets in one region of New South Wales. No challenge about age was made for 70 per cent of purchases, and proof of age was requested on only 15 per cent of occasions. The results suggest that legislation banning sales of cigarettes to minors requires strong enforcement procedures to be effective. PMID- 1296784 TI - Patterns of service utilisation following the 1989 Newcastle earthquake: findings from phase 1 of the Quake Impact Study. AB - A screening questionnaire was distributed to 5,000 adult members of the community six months after the 1989 Newcastle earthquake, with a response rate of 63 per cent (n = 3,007). The mean age of respondents was 46.7 years and 58 per cent were female. Subjects' earthquake experiences were rated in terms of weighted indices of exposure to threat and disruption. Psychological morbidity was measured using the General Health Questionnaire and the Impact of Event Scale. Subjects were asked to indicate which of a range of general and disaster-related support services they had used in dealing with the stressful effects of the earthquake. It was estimated that 21.3 per cent of the adult population used general and/or disaster-related support services. Users of these services reported greater exposure to threat and/or disruption and had higher levels of psychological distress than nonusers. However, a high level of use of general services and reliance on medical services were related more to psychological morbidity than degree of exposure to earthquake-related events. Overall, the Newcastle community's needs for assistance in the aftermath of the earthquake were effectively absorbed by the existing support services and the resources marshalled to supplement those services. Individuals and organisations mobilised following natural disasters need to be strengthened by enhancing the capacity of support service workers to identify and manage psychological distress in their clients. PMID- 1296785 TI - Public knowledge about characteristics of moles and melanomas. AB - In a study aiming to determine public knowledge about moles and melanomas 590 residents of Victoria aged 14 and over were interviewed in a face-to-face household survey. The majority believed that moles were primarily raised lesions. Recognition of the term melanoma was high (91 per cent), but many held misconceptions about key characteristics. Many thought an early melanoma was raised (20 per cent) or could be raised (42 per cent), compared with only 10 per cent who thought it was flat. Fifty per cent of respondents thought being ugly was a common characteristic. In response to photographs of skin lesions, a late melanoma, seborrhoeic keratosis and a squamous cell carcinoma were most likely to be identified as needing to be seen by a doctor, while a normal raised mole and two early melanomas were least likely. The data suggest that a large proportion of the community have misconceptions about the early signs of melanoma. Education programs are needed to inform the public that most early melanomas are flat. Strategies which might confuse this message, such as likening melanoma to moles, should be avoided. PMID- 1296786 TI - A survey of infertility, surgical sterility and associated reproductive disability in Perth, Western Australia. AB - Infertility, surgical sterility and associated reproductive disability were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Sixteen couples were omitted from analysis because of missing data. The proportion of couples affected by current infertility was 3.5 per cent (53 of 1,495), and 67.9 per cent of these (36 of 53) had a reproductive disability, meaning that they were unable to achieve their desired level of reproductive function. Those affected by surgical sterility accounted for 37.1 per cent (555 of 1,495), and of these couples 2.0 per cent (11 of 555) had a reproductive disability. Empirically, the prevalence of both infertility and reproductive disability peaked at ages 30 to 34 years in the female partner. Of the factors studied, infertility was associated with surgery for a ruptured appendix, a history of pelvic inflammatory disease and number of sexual partners. In 10 of the 47 couples with reproductive disability, contraceptive sterilisation had been a cause of later regret. Most other cases were due to infertility. Almost one half of couples with reproductive disability had sought treatment. The affected couples had at least one child from the current union in 23 of the 47 cases of reproductive disability. The results support the need for development of a strategy to prevent infertility and other causes of reproductive disability. PMID- 1296787 TI - A survey of contraceptive use and unplanned pregnancy in Perth, Western Australia. AB - Contraceptive use and unplanned pregnancy were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Twenty-one couples were excluded from analysis owing to missing data. The proportion of couples using contraception was 76.8 per cent (1,144 of 1,490), and all but three of the remaining couples gave a reason for nonuse. Among users, surgical sterilisation made up 42.3 per cent (484 of 1,144) of all methods, with a slight predominance of tubal ligation over vasectomy. Oral contraceptives accounted for just over half of nonsurgical methods. Comparisons with a Victorian survey performed in 1978 suggested that surgical methods and condom use may have increased, whereas use of oral contraceptives and intrauterine devices may have fallen. Unplanned pregnancies conceived during the 12 months before the interview affected 3.4 per cent (51 of 1,490) of respondents. The incidence of unplanned pregnancy was four times higher in couples with inconsistent usage patterns of contraception. PMID- 1296788 TI - Evaluating the petrol-sniffing prevention programs of the Healthy Aboriginal Life Team (HALT) AB - The evaluation of the Healthy Aboriginal Life Team's (HALT) petrol-sniffing prevention programs at Yuendumu, Kintore and the Pitjantjatjara Lands first required a specification of program outcome--which was not changed in the enumerated prevalence of petrol sniffing, but alteration in parental perceptions of the relevance and effectiveness of families' nurturant authority over recalcitrant youngsters. The evaluation then proceeded by a series of interviews with resident or ex-resident adults (Aboriginal and non-Aboriginal) of Yuendumu, Kintore, Kiwirrkurra, Ernabella, Indulkana and Fregon. Adults articulated their efficacy in different ways in each place. Some favoured the conclusion that HALT had helped them, others clearly identified HALT as an obstacle to or a distraction from the implementation of other preventive and curative community based action. We discerned a ferment of cultural adjustment in the distribution of authority over children among parents and welfare agencies. We caution against finding in HALT's successes a model procedure for benign interventions into such cultural adjustment. PMID- 1296789 TI - Smoking in aborigines and persons of European descent in southeastern Australia: prevalence and associations with food habits, body fat distribution and other cardiovascular risk factors. AB - As part of a population-base study of risk factors for heart disease, we aimed to establish the prevalence of smoking and to identify associations between smoking and other risk factors in Australian Aborigines (n = 306) and persons of European descent (n = 553) in two country towns. Smoking prevalence was first analysed as a dichotomy (current smokers compared with nonsmokers), and according to three levels of exposure (< 10, 10-20 and > 20 cigarettes per day), and two levels of nonexposure (never and former smoker). Other behavioural, biochemical and physical variables were included in multivariable analyses. Of the Aborigines, 64.4 per cent (95 per cent confidence interval (CI) 59.0 per cent to 69.8 per cent) were current cigarette smokers, compared with 22.8 per cent of non Aborigines (CI 19.3 per cent to 26.3 per cent). For persons aged 13 to 54 years, using the five categories of exposure, smoking in Aborigines again far exceeded that in non-Aborigines in all age groups (for males chi 2 = 72.8, for females chi 2 = 94.6, 4 df, P = < 0.0001 for both sexes). In non-Aboriginal females, the highest prevalence was in the youngest group (56 per cent of those aged 13 to 17 years). Food habit was associated with smoking. Subjects who ate meat without trimming the fat were more likely to smoke. In Australian country towns, Aborigines and all young women need smoking cessation programs. The nutritional status of smokers requires further study. PMID- 1296790 TI - Assessing community attitudes toward medical practitioner authority. AB - Despite the widespread belief that medical authority is under increasing challenge, no adequate research instrument has been available to measure relevant community attitudes. This paper reports the development of the Attitude Toward Medical Practitioners Scale (the AMPS). Samples of Australians (in total N > 1000) completed the AMPS, using three different procedures. The reliability of the scale, assessed by coefficient alpha, ranged from 0.80 to 0.86. A principal component analysis of the AMPS yielded loadings on each item exceeding 0.3 on the first unrotated factor; subsequent varimax rotation revealed dimensions associated with critical attitudes to doctors and evaluations of doctors' interpersonal competence and technical expertise. Positive and significant correlations between the AMPS and one measure of the General Attitude toward Institutional Authority (GAIAS) strongly suggested that the scale is consistent with generalised evaluations of community authorities. The specific validity of the AMPS was supported for each of three samples, using as validating criteria respondent ratins of the last doctor visited, satisfaction with the consultation and reported compliance with the doctor's advice. Significant improvements were found in the prediction of each of these criteria by the addition of the AMPS to contributions made by the GAIAS and the demographic variables, age and sex. The AMPS is an appropriate measure for assessing community attitudes towards medical practitioners conceived as institutional authorities, at least in the Australian context. PMID- 1296791 TI - Occupational injury and disease among patients presenting to general practitioners in a community health centre. AB - A prospective survey was conducted of all patients presenting over a six-month period to the primary medical care unit of a community health centre in an urban industrial area to determine the number and types of work-related injuries and disease, the causes, and details of the injured workers and their workplaces. Two hundred and eighty-three patients, 7.2 per cent of the total number of patients attending, were diagnosed as having a work-related injury or disease; 250 patients had occupational injuries and 33 had occupational diseases. The most common injuries were open wounds, sprains and strains, contusions and eye injuries; the most frequent diseases were musculoskeletal strain syndromes, dermatitis and respiratory conditions. Most of those injured were skilled tradesmen or labourers from small (less than 30 employees) or medium-sized (30 to 99 employees) manufacturing workplaces. In five of the local medium-sized workplaces, more than 10 per cent of the workforce presented with occupational injury or disease in the six months. The mechanisms of injury for common injuries such as back strain and eye injuries are described. Most patients were managed totally within the primary care setting. Thirty per cent of all patients surveyed received a worker's compensation certificate. It is possible that occupational diseases were underdiagnosed and that worker's compensation was underutilized. The information obtained from the survey is being used in planning prevention. PMID- 1296792 TI - General practitioner services under Medicare. AB - This paper examines how general practitioner numbers, bulk-billing rates and sociodemographic variables determined usage of general practitioners and services delivered over the period from 1984 to 1990. A 10 per cent sample of patient services, maintained by the Commonwealth Department of Health, Housing and Community Services, provided the data. Data were aggregated into 148 electorates. Separate regression analyses examined the determinants of the proportion of the population attending a general practitioner and of the number of general practitioner services delivered per patient. Determinants of the growth of these levels over the seven-year period were also examined. Region (metropolitan versus rural), age structure and general practitioner supply were significant factors in these analyses. Bulk-billing rates explained nine per cent of variance in patient numbers and 22 per cent of variance in service numbers after sociodemographic variables and general practitioner supply had been taken into account. The analyses suggest that bulk-billing and general practitioner supply influence the behaviour of patients and doctors and that the effect of bulk-billing is independent of indices of medical need. This implies that bulk-billing may increase service rates and this increase is not clearly directed to improving access to medically necessary services. Because no measures of treatment outcome are available. it is not possible to decide whether the effects observed represent an improvement in health care or are better seen as overuse by patients and demand inducement by practitioners. PMID- 1296793 TI - Accuracy of asthma death statistics in Australia. AB - Asthma mortality statistics issued by the Australian Bureau of Statistics (ABS) were compared with clinical data from a survey of asthma mortality. Deaths in Victoria from May 1986 to April 1987 containing 'asthma' in Parts 1 or 2 of the death certificate (N = 405) were reviewed. For each subject, the cause of death attributed by the Victorian Asthma Mortality Survey was compared with the ABS cause of death, by age and sex of the subject. Information on 393 of the 405 deaths investigated by the Victorian Asthma Mortality Survey was analysed. The ABS estimate of the total number of asthma deaths in Victoria was 47 per cent higher than the estimate of the Victorian Asthma Mortality Survey. In subjects under 50 years of age the two estimates were within 10 per cent. The difference between the estimates increased with age at death for persons over 50 years old and was equivalent for males and females. If the assessment by the Victorian Asthma Mortality Survey of the number of deaths due to asthma is accepted as accurate, then the ABS estimate of asthma deaths was reliable for those under 50 years of age. In those who died at an older age, the ABS significantly overestimated the number of deaths due to asthma in Victoria. PMID- 1296794 TI - Death certification in Western Australia--classification of major errors in certificate completion. AB - We aimed to develop a method to classify those errors in the completion of death certificates arising from misunderstanding of the certification process. We reviewed 430 Western Australian death certificates registered in March 1990 using a method devised to differentiate between major and minor errors. Major errors were found in 16 per cent of certificates (95 per cent confidence interval 12 to 20 per cent). The error rate did not vary significantly between city and country areas, nor between teaching hospitals and other locations. The method was validated on a separate sample of 120 certificates. It has potential as a tool to monitor a critical but neglected step in the production of mortality statistics and to assess understanding of the process of death certification. PMID- 1296795 TI - The rationing of health care: should Oregon be transported to Australia? AB - The Oregon Plan is an ambitious attempt to address the widespread problem in the United States of a growing number of individuals who are without private health insurance and are not eligible for federal assistance programs. Its aim is to provide universal access for all Oregonians, without increasing total health care expenditure, by restricting the cover of some treatments. It has aroused interest in Australia and elsewhere. The appeal of the Oregon Plan lies in its explicit approach to rationing, in community participation in setting priorities, and the use of a cost-effectiveness framework. This paper describes the beginnings and the development of the Oregon Plan, and compares the actual development of the Plan with the rhetoric. There is a gap between the rhetoric of the Plan and its reality. The Oregon plan should be considered in the context of the United States health care system. We compare the American problems with those facing the Australian health care system and conclude that the answer to the question of whether Oregon should be transported to Australia is no. Nevertheless there are elements of the rhetoric of the Plan which could be applied in rationing health care in Australia. PMID- 1296796 TI - QSAR, diagnostic statistics, and molecular modelling of antiallergic acrylamide derivatives. AB - Quantitative structure-activity relationships of antiallergic N-[4-[4 (diphenylmethyl)-1-piperazinyl]-butyl]-3-(3-pyridyl)acr yl-amide s were studied. It was shown that the biological action depends on lipophilic and steric substituent features; apolar but small groups improve activity. Diagnostic statistics indicated that the QSAR equation is relatively robust. It was hypothesized from molecular modelling that the substituents influence primarily the pharmacokinetic-toxokinetic behavior of the compounds. PMID- 1296797 TI - QSAR study of HMGR inhibitors: 7-(heteroaryl)-3,5-dihydroxy-6-heptenoic ( heptanoic) acids. AB - The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) inhibitory activity of pyridine- and pyrimidine-substituted 3,5-dihydroxyhept-6(E)-enoic acids and 7-(1H pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)-enoic (-heptanoic) acids was quantitatively analysed using hydrophobicity, molar refractivity, electronic and Verloop's steric parameters. The results obtained were comparable to the earlier findings of 7-(aryl/biphenyl)-3,5-dihydroxy-6-heptenoic (-heptanoic) acids. The R'4-substituent of the aryl substituent of heteroaryl moiety was found to influence the inhibitory activity through its steric and electronic properties, and the equations confirm that substituents with minimum steric bulk, positive polar and negative resonance constants lead to better inhibitory activity. The changes in the heteroaryl moiety of the inhibitors did not correlate with the activity. Probably, the heteroaryl moiety of the inhibitors may be serving as a skeletal framework to hold the surrounding hydrophobic substituents. PMID- 1296798 TI - Structure-activity relationships of N-n-propyl-2-(4-fluoro-3 hydroxyphenyl)ethylamine derivatives as dopamine receptor ligands. AB - A series of N-n-propyl-2-(4-fluoro-3-hydroxyphenyl)ethylamine derivatives obtained by introducing on nitrogen atom a 2-phenylethyl moiety (with aromatic nucleus substituted at 3 or 4 position with fluorine, chlorine or hydroxy and methyl groups), as well as a 2-cyclohexylethyl or 3-phenylpropyl groups were synthesized. These substituents can interact with the D2 accessory binding site pi 3. The affinities of new compounds for D1 and D2 subtypes of dopamine (DA) receptor were measured in a test involving displacement of [3H]SCH 23390 and [3H]spiperone, respectively, from homogenates of rat striatum. The new derivatives are selective for D2 sites, and are more potent than the parent compound N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3-hydroxyphenyl)ethylamine 2a. The N-n-propyl-N-[2-(4-hydroxyphenyl)ethyl]-2-(4-fluoro-3-hydroxyphenyl) ethylamine (11f) is the most potent and selective member in the series. Other derivatives are less effective but are as potent as the D2 agonist RU 24213. The results indicate that the pi 3 site is a rather large lipophilic pocket which can accommodate not only aromatic nuclei, but also the cyclohexyl group. PMID- 1296799 TI - Allograft rejection: the role of the cytokine network. PMID- 1296800 TI - Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis. AB - No biological parameter is currently available as a specific marker of multiple sclerosis (MS) activity. The aim of this study was to determine whether an evolution of the neurological disability is associated with a modified profile of cytokine production. Clinical disease activity was quantitated by the Kurtzke's expanded disability status scale (EDSS). Whole blood was stimulated with phytohemagglutinin (PHA) for 2 hours at 37 degrees C and the activated plasma was assayed for Tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta). Relapsing-remitting MS patients enduring a relapse (RRMS, in relapse) (721 +/- 58 pg/ml, n = 27) and chronic progressive MS (CPMS) patients (516 +/- 33 pg/ml, n = 17) had an higher TNF-alpha production capacity as compared to healthy subjects (143 +/- 25 pg/ml, n = 17), RRMS, stable patients, (123 +/- 11 pg/ml, n = 26) or other neurological diseases (OND) without immunological or inflammatory disease in the peripheral immune compartment (131 +/- 24 pg/ml, n = 14) (t test: p < 0.0001). IL-1 beta production was also significantly higher but to a lesser extent in the same conditions. Concentration of TNF-alpha was also found to be significantly higher in the cerebrospinal fluid (CSF) of CPMS patients (199 +/- 7.8 pg/ml, n = 7, p < 0.0001) but also in RRMS, in relapse (149 +/- 5.7 pg/ml, n = 11, p < 0.05) as compared to RRMS, stable (130 +/- 4.4 pg/ml, n = 7) or OND without inflammatory or immunological disease of the central nervous system (CNS) (142 +/- 6.2 pg/ml, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296801 TI - The biosynthesis of tumor necrosis factor during pregnancy: studies with a CAT reporter transgene and TNF inhibitors. AB - Tumor necrosis factor (TNF) is a protein hormone which mediates diverse inflammatory conditions, but which also may be involved in physiologic processes. To detect the expression of TNF as it might occur in normal tissues we developed a transgenic mouse line bearing a reporter gene construct in which the INF coding sequence and introns are replaced by a chloramphenicol acetyl transferase (CAT) coding sequence. In these animals, expression of CAT within tissues has been shown to reflect TNF production. We now report upon the pattern of CAT expression that is observed during normal pregnancy. CAT is constitutively expressed in both the fetal and maternal thymuses, and in the placenta, but in no other tissues. Placental CAT activity first becomes measurable at day 13 of gestation, peaks at day 16, and is maintained at high levels until parturition. Crosses between transgenic and non-transgenic mice clearly indicate that the trophoblast, rather than the decidua or uterus, is the source of CAT activity. A soluble TNF receptor/IgG heavy chain chimeric protein, which strongly inhibits TNF activity in vitro and in vivo, was shown to cross the placenta, gaining access to the fetal circulation when administered on the maternal side. However, the chimeric protein did not interrupt pregnancy, and had no obvious effect on fetal development, suggesting that TNF may not be required for completion of a normal gestation. PMID- 1296802 TI - Expression of CD23 by human bone marrow stromal cells. AB - CD23 is a surface antigen expressed by a variety of human hematopoietic cells and shown to display multiple biological functions. In present work, we assayed CD23 expression by human bone marrow (BM) or by stromal cells derived from this tissue. While freshly isolated BM-cells showed low CD23 expression, a subset of long term BM-culture (LTBMC)-derived stromal cells expressed CD23 mRNA at high levels in their steady state and secreted soluble CD23 in their culture supernatants. To assay the role of CD23 in LTBMC, these cultures were initiated in the presence of neutralizing anti-CD23 mAb. A dramatic decrease in total numbers of hematopoietic cells and CFU-GM recovery was observed in these cultures as compared to controls. These data suggest a role of CD23 expression in stroma cell functions and further confirm the ability of this antigen to regulate human hematopoietic cell development. PMID- 1296803 TI - Simultaneous quantitation of cytokine mRNAs in interleukin-1 beta stimulated U373 human astrocytoma cells by a polymerisation chain reaction method involving co amplification with an internal multi-specific control. AB - The measurement of cytokine mRNA levels is of fundamental importance in the understanding of diverse pathological states. We present a simplification of a polymerase chain reaction-based technique which permits the simultaneous measurement of up to 20 cytokine mRNAs, together with those of several other cellular products, including beta 2-microglobulin and beta-actin. The technique makes use of internal standards bearing multiple PCR primer sites which are identical to those on the mRNAs to be assayed. Known quantities of the standards are added to the cellular RNA and the mixture is co-reverse transcribed and co amplified. The simplifications described here are based on the fact that each pair of amplicons accumulates in a constant ratio even in the plateau phase of amplification. As a result, no preliminary experiments to determine the limits of the exponential phase of amplification are necessary; the same number of cycles may be chosen for all the mRNAs to be measured, whatever their level in the mixture might be; pipetting errors are avoided since all calculations are based upon the relative quantities of co-amplified material. Here we illustrate the method through a quantitative study of the expression of cytokine mRNAs in U373 human astrocytoma cells before and after stimulation with IL-1 beta. Quantitation was carried out either by incorporating radioactivity in the amplicons or by fluorescence measurements after propidium iodide staining. Only very low numbers of transcripts for IL-6, IL-8, CSF-1, MCP-1 and either Gro alpha or Gro beta were detectable in unstimulated cells. The levels of these cytokine mRNAs increased dramatically following IL-1 beta stimulation and, in addition, transcription of IL-1 beta, TNF alpha, GM-CSF, G-CSF, Gro gamma and MCP-1, some of which have not previously been detected in U373, was initiated in the stimulated cells. At the same time we found that transcripts for IL-2, IL-3, IL-4, IL-5, IFN gamma, huMlP1 alpha and huMlP1 beta were totally absent in this cell line. These results suggest a potentially important role for astrocytes in the local amplification of inflammatory responses in the brain. PMID- 1296804 TI - Subcellular distribution in vivo of testosterone and salt extractability of nuclear androgen complexes in the prostate and prostatic adenocarcinoma: effect of estrogen treatment. AB - The distribution of injected [3H]testosterone into nuclear (Nt) mitochondrial microsomal (Mp) and cytosolic fractions (Cs) obtained from hormone-dependent R 3327 Dunning tumor, dorsal prostate, ventral prostate and heart ventricle, as a non-target tissue, was studied. Since it has been suggested that salt resistant steroid receptor complexes may represent acceptor sites, extractability of nuclear androgen complexes with high KCl (0.6 M) solution was also determined. Both orchiectomized (Or) and estrogen treated (E2) rats were used. The distribution of bound radioactivity between Nt and Cs fractions was very similar in tumors, dorsal and ventral prostate, being approximately 50% and 10% in Nt and Cs, respectively. In heart the corresponding figures were 15% and 12%, respectively. The concentration of radioactivity/mg protein in nuclear KCl extract (Ne) from tumors was approximately 10-fold higher than that in the salt resistant (Nr) fraction and also nearly 10-fold higher than that in Cs. Similar distribution patterns were observed in dorsal and in ventral prostate, but the concentration in Ne from ventral prostate was higher than that from tumors or dorsal prostate. Both total and bound radioactivity in Cs from heart was similar to that in the tumors, whereas the concentration in Ne from heart was < 2% of that in Ne from tumors. No significant differences were found in the distribution of radioactivity in tumors or tissues obtained from Or or E2 rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296805 TI - Leiomyoma-derived growth factors for smooth muscle cells. AB - The presence of growth substance(s) for smooth muscle cells and fibroblasts was documented in extracts of human leiomyoma tissues (Koutsilieris et al, Am. J. Obst. Gynecol. 163: 1665-1670, 1990). In this study leiomyoma tissues (700 grs) obtained at surgery were extracted and purified using CM-sepharose, heparin sepharose and reverse-phase high performance liquid chromatography (r-HPLC). The mouse NIH/3T3 cell fibroblasts (ATCC-CRL 1658) and the rat smooth muscle cells A10 (ATCC-CRL 1476) were used as indicator bioassay systems assessing the proliferative effect (tritiated-thymidine incorporation and cell number) of leiomyoma extracts. The profile of peptides purified by cm-sepharose, heparin sepharose and by r-HPLC was analyzed by standard SDS gel electrophoresis. An overall 50,000 fold purification was achieved of a preferentially acting material on rat aorta smooth muscle cells (A10 cells). This material possessed mitogenic activity equivalent to epidermal growth factor (EGF) on A10 smooth muscle cells, in vitro. We believe that the final chemical definition of such leiomyoma-derived growth substance with preferential action on smooth muscle cells may elucidate the paracrine and/or autocrine interactions among myometrial cells and thus could provide new clues for the pathogenesis of uterine leiomyomas. PMID- 1296806 TI - Induction of anti-Escherichia coli activity in mice by phenothiazines, benzo[a]phenothiazines and benz[c]acridines. AB - The abilities of 14 phenothiazines, 8 benzo[a]phenothiazines and 12 benz[c]acridines to induce anti-Escherichia coli activity in mice were compared. Pretreatment with several benzo[a]phenothiazines or benz[c]acridines protected mice from lethal infection of Escherichia coli in a dose-dependent manner, whereas most of the phenothiazines induced much weaker anti-Escherichia coli activity. However, direct contact of Escherichia coli with these compounds or their administration just after bacterial inoculation were ineffective. These data suggest the immunopotentiation activity of benzo[a]phenothiazines and benz[c]acridines. PMID- 1296807 TI - Stimulation of host resistance against tumors by glycyrrhizin, an active component of licorice roots. AB - The effect of glycyrrhizin (GR), a Chinese herbal drug extracted from licorice roots, on the host resistance to tumors was investigated in a murine system. Administration of GR to BALB/c mice, which were inoculated s.c. with 1 x 10(6) cells/mouse of Meth A tumors, resulted in either no antitumor effect (8/20, 40%), a delay in tumor growth (9/20, 45%), or elimination of tumor growth (3/20, 15%) in these mice. In addition, the incidence of Meth A solid tumors was inhibited by GR when mice were inoculated with 1.5 x 10(4) cells/mouse or less of Meth A tumor cells, but not 7.5 x 10(4) cells/mouse or more. These results indicate that in this murine tumor system GR has a very weak antitumor effect. When GR at a dose of 20 mg/kg was administered to mice immunized with allogeneic lymphocytes 1 to 9 days after the immunization, the generation of suppressor macrophages (S-M phi) was clearly reduced as compared with that of S-M phi generated in immunized controls. In addition, when allospecific CTL (allo-CTL), which were generated in alloimmunized mice treated with GR followed by in vitro stimulation with allogeneic lymphocytes in a mixed lymphocyte reaction, were adoptively transferred to tumor-bearing mice treated with GR, the antitumor activity of allo CTL derived from immunized mice treated with GR was markedly enhanced as compared with that of allo-CTL from immunized mice. Furthermore, established solid tumors were completely eliminated when interleukin-2 immunotherapy was performed in these mice in combination with GR treatments, but not interleukin-2 or GR alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296808 TI - Detection of IgM antibodies to Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci from Japanese infants and children with pneumonia. AB - Chlamydia trachomatis (C. trachomatis) is now well established as a pathogen of neonatal inclusion conjunctivitis and infantile pneumonia. C. pneumoniae (TWAR) and C. psittaci also cause pneumonia and other respiratory infections. Serum samples from 223 Japanese infants and children with pneumonia were tested for IgM antibodies to C. trachomatis, C. pneumoniae and C. psittaci. IgM antibodies to C. trachomatis were measured by an enzyme immunoassay (EIA) and by a microimmunofluorescence (MIF) test. IgM antibodies to C. pneumoniae and C. psittaci were determined by MIF. Of 223 patients, 48 (21.5%) were positive for IgM antibodies to C. trachomatis, 11 (4.9%) were positive for C. pneumoniae and 5 (2.2%) were positive for C. psittaci. From nasopharyngeal swabs collected from 87 infants with pneumonia (0 to 1 year of age), we attempted to isolate C. trachomatis with tissue culture. C. trachomatis was isolated from 23 (26.4%) of 87 infants with pneumonia, and IgM antibodies to C. trachomatis were detected in 17 (19.5%) of them. Our data suggest a role for chlamydial infection in childhood pneumonia beyond infancy with both C. trachomatis and C. pneumoniae being contributing pathogens. PMID- 1296809 TI - Differential effects of butyrate derivatives on human breast cancer cells grown as organotypic nodules in vitro and as xenografts in vivo. AB - The antiproliferative and cytodifferentiating effects of a new stable butyric derivative, monobut-3, were compared using human MDA-MB-231 breast cancer cells grown in three dimension as either in vitro tumor nodules or in vivo xenograft tumors. In in vitro tumor nodules, monobut-3 exhibited marked growth inhibitory effects consistent with the results obtained in monolayer cell cultures. Some functional cell differentiation was also detected in treated nodules. In in vivo xenografts, monobut-3 significantly decreased MDA-MB-231 tumor take but did not affect the rate of tumor growth. No difference was noted in the histological characteristics of the xenografts between untreated and treated mice. Moreover, once monobut-3 treatment was discontinued, tumor growth rapidly resumed in tumor free animals. The decreased efficacy of monobut-3 in in vivo MDA-MB-231 xenografts as compared to in vitro tumor nodules indicates that factors related to host environment may still limit the clinical effectiveness of this compound. PMID- 1296810 TI - In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum. AB - In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic phosphate and phosphomonoesters and a decrease of phosphocreatine. Fast growing tumours and early stage of regrowth after treatment presented a higher phosphocreatine/beta NTP ratio. Following CDDP treatment, 31P metabolite ratios and pH were significantly altered compared with age-matched controls, as early as 6 hours after treatment. Although necrotic area was clearly visible in MRI, no treatment effect could be detected on the images of treated tumours. PMID- 1296811 TI - Morphohistochemical characterization of suramin--induced chronic toxicity in rat kidney. AB - The effects of a chronic administration of suramin were evaluated on renal parenchyma of young rats. Animals were given suramin 18 mg/kg i.p. twice a week for two months, a treatment schedule equivalent to that used in cancer patients. At the end of the treatment, suramin concentrations in plasma and kidney were assayed and a morphohistochemical examination of renal parenchyma was carried out. Marked and widespread alterations were detected in both cortex and medulla and were associated with elevated tissue suramin levels exceeding 5 mg/g of tissue. The present data demonstrate that suramin induces a severe chronic renal damage in the rat, associated with high drug tissue levels. PMID- 1296813 TI - Measurement of platelet volume using a channelyzer: assessment of the effect of agonists and antagonists. AB - Platelets undergo morphological changes prior to aggregating. This phenomenon is known as the platelet shape change (PSC) and is usually accompanied by at increase in median platelet volume (MePV). We evaluated MePV changes in human platelet rich plasma (PRP) using a high resolution pulse-height analyser ("channelyzer"). Increases in MePV were induced by the addition of low concentrations of known aggregating agents. These agonists showed different patterns in terms of potency, duration and reversibility. PMID- 1296812 TI - In vivo cytotoxicity and antineoplastic activity of a transferrin-daunorubicin conjugate. AB - Transferrin, the major iron-binding protein in the plasma of vertebrate species, is an essential growth factor for proliferating malignant cells. The specific receptor binds diferric transferrin and is endocytosed into the cell. We would like to take advantage of this physiologic phenomenon using an active transferrin daunorubicin conjugate to target cancer cells. We have compared the in vitro and the in vivo activity of free daunorubicin and of daunorubicin transferrin conjugate on cancer cells. The results suggest that our conjugate is less toxic and more active upon malignant cells than the free drug, daunorubicin, while being less toxic for normal cells. PMID- 1296814 TI - Differential changes of prostanoid synthesis by the gastrointestinal tract, mesenteric vasculature and hepatic portal vein of diabetic rats: comparison between pair and ad libitum feeding. AB - The synthesis of the prostaglandins (PG) I2 (measured as 6-oxo-PGF1 alpha), E2, E2 alpha) and thromboxane (TX) A2 (measured as TXB2) by the mucosal and muscular portions of the stomach, duodenum, jejunum, ileum, mesenteric vessels, hepatic portal vein and two arteries (carotid and aorta) was investigated in long term streptozotocin-induced diabetes mellitus (DM; fed ad libitum and pair fed). In all regions of the gastrointestinal tract there were no changes in PG synthesis (per unit weight of tissue) in diabetic rats (pair fed or fed ad libitum) compared to controls. However, there were marked increases in PG synthesis (up to 3 fold) by the mesenteric vasculature and hepatic portal vein in diabetic animals fed ad libitum and in pair fed diabetic rats and decreases in the aorta and carotid artery. These data suggest that increases in PG synthesis by the splanchnic vasculature may constitute a specific adaptive response to DM. The similarity of the responses of pair fed rats to those of rats fed ad libitum indicates that DM and not hyperphagia is the likely determinant of these adaptive changes. Given that increased splanchnic blood flow enhances nutrient uptake (both known to occur in DM), the increase in splanchnic vascular PG synthesis, in particular of vasodilatory PGI2, may contribute to enhanced nutrient uptake. PMID- 1296815 TI - Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17. AB - Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed. PMID- 1296816 TI - Secondary structure analysis identifies a putative mouse protein demonstrating similarity to the repeat units found in CDC4, the G protein beta subunits and related proteins. AB - The predicted protein product of an anonymous clone isolated from a cDNA library prepared from 12 day post coitum (p.c) embryonic mouse heart tissue demonstrated the same segmental repeats previously identified in the cell division control protein, CDC4 and the G protein beta 1 subunit. A search of the protein database subsequently identified three other classes of protein containing the repeat. Secondary structure analyses performed on the repeat sequences revealed a high degree of conservation suggesting that the repeat motif performs a specific function in a diverse range of proteins. PMID- 1296818 TI - Cloning and sequencing of human kappa-casein cDNA. AB - A cDNA encoding kappa-casein of human milk was cloned and sequenced. The kappa casein cDNA was isolated from a lambda gt11 library generated from mRNA prepared from a mammary gland biopsy obtained from a lactating woman. The library was screened with polyclonal rabbit antibodies raised against purified native kappa casein. The obtained nucleotide sequence contained an ORF sufficient to encode the entire amino acid sequence of a kappa-casein precursor protein consisting of 182 amino acids. This includes a tentative signal peptide of 20 amino acids and a processed protein of 162 amino acids. PMID- 1296817 TI - The glgB gene from the thermophile Bacillus caldolyticus encodes a thermolabile branching enzyme. AB - We have cloned the structural gene for the Bacillus caldolyticus glycogen branching enzyme (glgB) in Escherichia coli. The glgB gene consisted of a 1998 bp open reading frame (ORF) encoding a 78,087 Da protein, which was highly similar to the Bacillus stearothermophilus branching enzyme. The 5' end of a second gene that encoded a protein with extensive similarity to E. coli ADP-glucose pyrophosphorylase (ADPGP) partly overlapped the 3' end of the glgB gene. A putative promoter recognized by Bacillus subtilis RNA polymerase containing the sigma factor H (E-sigma H) preceded the genes. These data suggest that in contrast to the situation observed in B. stearothermophilus, the genes involved in glycogen synthesis in B. caldolyticus are clustered on the chromosome, and are presumably coordinately expressed during the early stages of sporulation. An incomplete third gene started upstream of B. caldolyticus glgB. This gene was highly similar to a gene found directly upstream of B. stearothermophilus glgB, which encodes a putative membrane protein with unknown function. The B. caldolyticus glgB gene was expressed in E. coli and B. subtilis. Surprisingly, the branching enzyme appeared to be thermolabile, the temperature of optimal activity being only 39 degrees C. PMID- 1296819 TI - Nucleotide sequence of a Drosophila melanogaster gene encoding a calreticulin homologue. AB - A Drosophila melanogaster gene encoding a homologue of the mammalian ER calcium binding protein, calreticulin, was cloned and the nucleotide sequence determined. Four exons can be identified, contained within 1700 bp of sequence, separated by introns of 124, 266 and 92 bases. The exons encode a 389 amino acid protein which may be a precursor form as it includes an N-terminal signal region of 17 residues that could potentially be cleaved to form a mature protein. The C-terminal region of the protein contains the established pattern of polyacidic clusters, common to calreticulins of other species and ends in the ER retention signal HDEL. Excluding the N-terminal signal region, the Drosophila protein amino acid sequence has a 67% identity to mammalian calreticulins and the length and acidity of the C-terminal zone in the insect protein are intermediate between higher mammalian and lower nematode values. PMID- 1296820 TI - Isolation of different brain-specific isotypes of alpha-tubulins from chum salmon (Oncorhynchus keta). AB - An alpha-tubulin cDNA clone, pTUB5 (1496 bp), encoding a protein of 444 amino acids (mol. wt. 48,840), has been isolated from the brain of Pacific salmon, Oncorhynchus keta. Partial sequence data were also obtained for two other alpha tubulin isotypes, pTUB6 and pTUB9, which are similar in sequence to pTUB5 except in the carboxy region of the protein. This region of alpha-tubulin has previously been shown to be important for the binding of microtubule associated proteins suggesting that the isotypes described in this study may represent differentially controlled elements of the neural tubulin population. The isotypes show brain specific expression and are the first tubulins to be reported for this tissue in fish. PMID- 1296821 TI - Nucleotide sequence of the mitochondrial 5S rRNA gene from lupine (Lupinus luteus). AB - A lupine mitochondrial clone containing 5S rRNA gene is characterized. The gene is located on the same strand as 18S rRNA and separated from it by 190 nucleotides. The intergenic region in different plants shows high degree of homology. In the case of lupine and soybean 43 nucleotides upstream of 5S rRNA gene exhibits 100% of homology. Comparisons of lupine 5S rRNA gene sequence with other plant mitochondrial 5S rRNA genes displays high degree of homology (from 89.8% to 95.8%). PMID- 1296822 TI - Utilization of rat and human sera to carry out incubation and perifusion of pancreatic islets. AB - Incubation of isolated pancreatic rat islets in a medium consisting of fresh rat or human sera and the measurement of insulin secretion after 60 min in the presence of 6.0-7.0 and 16.7 mM of glucose, were carried out. Perifusion experiments with isolated rat islets preincubated in the presence of rat or human sera and 0.2 mCi/mL of 45Ca2+ were also performed, and 45Ca2+ outflow rate and insulin secretion were analyzed. In both experiments, the usual islet responsiveness to glucose stimulation was preserved when compared with experiments in which Krebs-Henseleit (K-H) buffer was used as the medium. The results obtained demonstrate that both rat and human sera can be used as media for islets perifusion and incubation experiments, thus allowing for the effect(s) of circulating substances on insulin release to be examined. PMID- 1296823 TI - Administration of the anesthetic isoflurane to mice: a model for acute intermittent porphyria? AB - The effects of isoflurane, a commonly used volatile anesthetic, on the activity of some haem enzymes in liver, kidney, and blood, and glucose content in liver and blood were studied. Mice were injected with different doses of the drug (0.5 6 mL/kg) and killed at varying intervals after injection (5-240 min). Within this dose range, optimal effects on alteration of haem metabolism were obtained at 2 mL/kg. The time-response profile for each enzyme was different. Blood porphobilinogenase (PBGase) and deaminase showed lower activities 20 min after anesthesia. This diminution coupled with the induction of delta-aminolevulinate synthetase activity observed soon after anesthesia (5 min) would fit well with the expected biochemical changes occurring in acute intermittent porphyria, indicating that this may be a suitable animal model for this disease. PMID- 1296824 TI - A novel method for the release and collection of dermal, glandular secretions from the skin of frogs. PMID- 1296825 TI - Effects of milrinone on lung water content in dogs with acute pulmonary hypertension. AB - To evaluate the effects of milrinone (MIL) on hemodynamics and lung water content, we used 10 mongrel dogs with pulmonary hypertension (PH). To induce pulmonary hypertension, we administered two injections of glass beads stirred in saline to dogs. Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance significantly increased following induction. Milrinone, which inhibits cyclic AMP phosphodiesterase-(PDE) demonstrated pulmonary vasodilation, indicated a reduction in these two parameters. To clarify the drug mechanism, we measured lung water content as extravascular lung thermal volume (ETVL) using a thermo/sodium double-indicator dilution method. The induction of pulmonary hypertension produced a transient reduction in extravascular lung thermal volume. The parameter remained constant following milrinone administration, whereas the control showed a gradual increase. Of the 10 dogs, five were killed to measure gravimetrically the volume of lung water content as a comparison with extravascular lung thermal volume. We concluded that milrinone produced pulmonary vasodilation which induced a reduction in the transmural capillary pressure gradient according to Starling's hypothesis. This study suggests that the reduction in the transmural pressure gradient induced by milrinone may also prevent the re-elevation in extravascular lung thermal volume. Milrinone increases the cyclic AMP level in the endothelium and in the platelet which may affect either directly or indirectly the permeability of capillary endothelium. PMID- 1296826 TI - Analysis of concentration-response relationships by seemingly unrelated nonlinear regression (SUNR) technique. AB - In performing statistical evaluation of concentration-response relationship in pharmacological studies, all the commercially available statistical packages assume each data point is an independent measure of the drug response, and do not account for the dependence between the multiple measurements taken from the same subject (tissue, animal, or sample). Seemingly unrelated nonlinear regression (SUNR) is a statistical technique that takes into account both within-and between subject variance. This technique has been implemented in an SAS-based interactive program called SUNR. The statistical analyses are based upon the original work by Gallant (Gallant, 1975, J Econometrics 3:35-50; Gallant and Goebel, 1976, JASA 71:961-967), which has been further developed by Muller and Helms (1984) (Presented at ASA meeting in Washington, D.C.) To test this program, we have analyzed both simulated and actual data with SUNR, comparing our results to those of several popular statistical programs. All the programs yielded essentially the same estimates for the EC50, minimum and maximum response in both the simulated and experimental data sets. However, our results differed markedly from the commercial packages in the estimates of standard errors associated with the estimated maxima. When analyzing simulated data, which were far less noisy than the experimental data, differences between the analyses were minimal. However, in the analyses of experimental data, the standard errors calculated by the commercial programs appear to significantly underestimate the standard error. Using SUNR, however, the 95% confidence limits on the maxima are markedly wider, and, importantly, always cover the observed actual data range. PMID- 1296827 TI - Efficacy of various water-soluble chelator molecules in the liposome-mediated macrophage "suicide" technique. AB - In earlier studies, we described a technique for the "in vivo" depletion of macrophages, using liposome-encapsulated dichloromethylene bisphosphonate (C12MBP). The aim of the present study was to compare the effects on macrophages of various other liposome-delivered Ca2+ chelators: EDTA, DTPA, and EGTA. It appeared that both EDTA and DTPA as well as Ca(2+)-and Cu(2+)-EDTA complexes were also effective in the elimination of splenic macrophages when encapsulated in liposomes and intravenously injected. EGTA, a well-known and frequently used Ca2+ chelator, had no effect. PMID- 1296828 TI - Method for study of endothelium-dependent vasodilatation in rabbit intrarenal arterial network. AB - The objectives of this study were twofold: 1) to determine whether a microdissected rabbit intrarenal arterial network (IAN), consisting mainly of interlobar, arcuate, and interlobular arteries exhibits endothelium-dependent vasodilatation, and 2) to establish a means of selectively abolishing this response. The IAN was perfused at a constant flow with heated-oxygenated Krebs bicarbonate buffer through the main renal artery, and evoked responses were limited to vessels distal to the renal artery. A decrease in perfusion pressure reflected a vasodilator response, after vascular tone had been induced by intraarterial infusion of phenylephrine. Bolus injections of acetylcholine produced graded endothelium-dependent vasodilator responses, whereas glyceryl trinitrate caused endothelium-independent responses. Manual de-endothelialization was accomplished by gently stroking the IAN and at the same time removing any remaining glomeruli. This procedure blocked the response to acetylcholine, but not to glyceryl trinitrate (n = 6). A 10-min infusion of NG nitro-L-arginine (NArg) (4 x 10(-5)-3 x 10(-4) M) into the IAN also selectively attenuated the response to acetylcholine (n = 7). The third procedure, consisting of a 10-min infusion of 22-44 mM hydrogen peroxide into the IAN also attenuated the response to acetylcholine, but not to glyceryl trinitrate in nine of 12 experiments. This investigation demonstrates that intrarenal arteries are capable of undergoing endothelium-dependent vasodilatation, and the potential use of the IAN for further study of renal endothelium-derived vasoactive factors. PMID- 1296829 TI - Guidelines for the management of hyperlipidaemia in general practice. Towards the primary prevention of coronary heart disease. Royal College of General Practitioners. PMID- 1296830 TI - [The management of the development of occupationally important qualities for the purpose of improving the training of flight personnel]. AB - The issues of purposeful development of occupationally important qualities (OIQ) of the pilots using a specially devised set of psychological, pedagogical, psychophysiological methods are studied. Evidence for an effect of the applied methods on the development of OIQ, success and reliability of flying activity is presented. Some mechanisms of creating an integral system of OIQ during pilot training are discussed. The peculiarities of OIQ influence on specific aspects and parameters of pilot activity including a real flight are considered. The views on the patterns of creating the professional flying abilities, their place in the structure of a pilot fitness for flying are discussed. PMID- 1296831 TI - [Age-related changes in the hemoglobin concentrations and erythrocytes of pilots]. AB - Longitudinal retrospective study has revealed the changes in the health of 706 pilots and air navigators and in the hemoglobin (Hb) and erythrocyte levels in peripheral blood once within a 5 year period. The duration of an examination is 10 years and even longer. It is established that the Hb concentration increased with an increase of the age. At the age of 20-30, this parameter is lower in persons being healthy for a long time. An analysis based on curve plotting of the remainder of life time indicated that the high level of Hb and high mean concentration of Hb in the erythrocytes have an adverse effect on the health and flight fitness. The regularities are noted within the normal values and validate a differentiated approach to evaluating the results of diagnostic examinations instead simplified normal-non-normal estimates. PMID- 1296832 TI - [Psychosomatic status and the quality of the piloting in flyers during geomagnetic disturbances]. AB - After using the psychological tests, namely Minnesota Multiphasic Personality Inventory (MMPI) and Luchaire 8-color test, a large group of pilots was divided into the individuals with high and low levels of anxiety. The highly anxious persons as opposed to those with a low level of anxiety are characterized by a more anxious level of operating during the quiet days free from magnetic disturbances. On heliogeomagnetic exposures, the pilots with a high level of anxiety unlike those with a low anxiety level operate at a new, even more intensive homeostatic level which is accompanied by a decreased functional activity of the central nervous system. The latter leads to a sharp decline in flying skills. Since there have been no significant changes in the physiological status and flying skills of the pilots with a low anxiety level during magnetic disturbances, it should be considered that the high level of anxiety is the risk of heliometeolability and flight safety. The ways to correct the high level of anxiety are developed. PMID- 1296833 TI - [The characteristics of the action of ethanol in operators with different states of the skin tissue basophils]. AB - The changes in some parameters of an operator activity after ethanol administration at a dose of 1.9 g/kg body weight in 10 men doing the job of two dimensional compensatory tracking in simulator, have been studied. In this case, the population state of tissue basophils (mast cells) of the body by studying the amounts of various structural and metabolic forms of these cells, contained in the skin biopsies, was studied. The degree of deterioration in operator activity was evaluated separately for the subjects with the population characteristics of tissue basophils higher or lower than mean values. It is indicated that the subjects with a low initial number of tissue basophils exhibiting signs of a holocrine-typed secretion and with a more pronounced response of these cells to ethanol were characterized by a significantly higher degree of the impairing many parameters of operator activity. Such differences were especially marked immediately after ethanol administration and practically lacked 12 hours after. PMID- 1296834 TI - [The circadian rhythmicity of human orthostatic tolerance]. AB - The results of studying the daily rhythmicity of orthostatic tolerance of blood system in practically healthy men are presented. The orthostatic test was performed 6 times a day with a 4-hour interval. The parameters of systemic, cerebral and peripheric hemodynamics have been recorded. It is found that a degree of a change in an intensity of cerebral blood supply experiences the marked variations depending on time of day. The day-night cycling of orthostatic tolerance of cerebral circulation is greatly determined by the biorhythm of the responses of arterial vessels of the lower extremities, i.e., by the natural periodization of blood redistribution processes. The highest orthostatic tolerance is noted at 3 to 11 a.m. and the lowest one at 3-7 p.m. PMID- 1296836 TI - [Metabolism in cosmonauts: the results of biochemical research on the blood of the crew members of the 7 prime expeditions on the Mir orbital space complex]. AB - The pre- and postflight biochemical analyses of the blood of 16 cosmonauts flown aboard Mir orbital station over 125-366 days revealed the changes in carbohydrate, lipid and protein metabolism being in line with the present-day ideas about the space flight effects on the human metabolism. A particular individual pattern of the responses and the absence of correlation with flight duration of space expeditions ranging from 4 months to a 1 year, are noted. PMID- 1296835 TI - [Human blood biochemical parameters under the conditions of an arid zone]. AB - Seven participants of 23 day walking march in an arid environment have been examined. Biochemical analysis of blood serum made on Day 2 of marching revealed a decrease in the levels of glucose, triglycerides and an increase in the concentration of non-esterified fatty acids which the authors characterize as the state of moderate stress in an acute period. PMID- 1296837 TI - [Microwaves and the visual analyzer]. AB - The results of studying an effect of microwaves on the different regions of visual analyzer are investigated. The morphofunctional changes at the light-optic and electron-microscopic levels are revealed. The changes involve not only peripheric area of visual analyzer but also its central regions. Some epidemiologic observations are indicative of: altered sizes of blind spot; decreased magnitudes of optic rheobase and chronaxy; color vision disorder; increased diastolic pressure in central artery of the retina. Study of bioelectrical activity of the retina enabled some investigators to make a conclusion about a reaction disorders occurring in the subcortical visual centers. It is noted that the animal studies not always explain unequivocally the microwave effects on the visual analyzer. PMID- 1296838 TI - [The effect of moderate altitude on the maintenance of a good health status and high physical work capacity in cosmonauts over the course of a long period of time]. AB - The development of the methods to maintain good health and high performance and occupational longevity of cosmonauts is an urgent problem. For this end, an effect of periodic (1-2 times a year) training in mid-lands on working and functional capacities of cosmonauts being members of cosmonauts corps for extended periods of time (20 years) was studied; the results of 40 trainings in mid-lands at 1,600 to 2,400 m above sea level are summarized. Before, during and after training, the physiological and physical parameters of the body (BP after Korotkoff, HR, VO2max) during exercise bicycle ergometer tests as well as the time of running on treadmill at a rate of 4.5 m/s to failure have been examined. The experimental findings indicated that after terminating physical training in mid-lands the major group of test subjects exhibited a significant decrease in HR as compared to the control value. During acclimatization, the arterial pressure (systolic and diastolic) measured when exercising on bicycle ergometer at 600 and 1000 kgm/min also reduced. As a result of improving the measured parameters after acclimatization to mountain environments the total body tolerance increased. A cumulative effect of the regular stay in mid-lands appears to change VO2max which did not decrease in man with age and the performance value (after i.v. Aulik classification) in the 40-49 age group subjects became very high. PMID- 1296839 TI - [Vestibulo-oculomotor reactions during immersion hypokinesia]. AB - The results of studying the spontaneous oculomotor responses and those induced by vestibular and visual stimulation in 30 test subjects exposed to a 3-day dry immersion are presented. The subjects were tested every day under conditions of free diving and during additional tactile-proprioceptive, optokinetic and vestibulo-optokinetic stimulation. It is indicated that an exposure to immersion is inherent in an increased amplitude and rate of spontaneous floating movements of the eyes and in 30 percent of cases in: developing of spontaneous nystagmus; decreasing of an accuracy of fixed turns and tracking; facilitating of oculomotor responses during optokinetic and optovestibular stimulation. When used an additional support, on Day 0-1 after optokinetic and optovestibular stimulation on Days 2-3 of immersion the tested oculomotor responses were improved. PMID- 1296840 TI - [The humoral immunity indices of rhesus monkeys under the action of extreme factors in space flight]. AB - Some features of nonspecific resistance of rhesus monkeys (G and A immunoglobulins and C3 complement component) are studied. Standards of IgG, IgA and C3 complement component in healthy rhesus monkeys are determined. The changes in the parameters of nonspecific resistance of the animals in all stages of their preflight training and shortly after flight experiment are examined. These alterations were appeared first of all as an increase in IgA level. PMID- 1296841 TI - [The hemodynamics in monkeys during head-down tilt hypokinesia at angles of -6 and -20 degrees]. AB - Hemodynamic changes in the monkeys (2 groups of 3 animals each) during 6 degrees and 20 degrees head down tilts (HDT) of various duration have been studied. An increase of the arterial blood pressure and linear velocity of the blood flow in the common carotid artery was noted immediately after HDT followed by a compensatory decrease of the values. A significant decline in orthostatic tolerance after 20 degrees HDT with developing a precollaptoid state is indicated. The changes of a circulation pattern in the common carotid artery bed are induced by a cranial shifting of the body fluids. PMID- 1296842 TI - [The healing of bone fractures in rats during the readaptation after a 14-day head-down suspension]. AB - Histological, histochemical and histomorphometric methods have been used to study an effect of a 14-day head-down suspension on healing the fractured fibular diaphysis in the rats traumatized immediately after suspension. The study of the fibulae on Days 11 and 17 following an operative fracture indicated that both in control and experimental rats the ends of fractured bones were tightly interconnected by the calluses. A comparative study of the calluses and their structural components as well as detailed investigation of histological structure of calluses on the 11th and 17th post-traumatic days did not reveal significant differences between control and experimental animals. Furthermore, the rate of cartilage replacement by spongy bone tissue in calluses of experimental animals was even somewhat higher than that in control rats. Thus the data obtained give ground to believe that in a readaptation period after 14-day suspension resulting in the osteoporotic changes of weight-bearing bones a repair process in the bones is rapidly normalized and in some parameters exceeds it in control animals. PMID- 1296843 TI - [The dynamics of the central and peripheral blood circulation in waking rats in the first 24 hours of head-down tilt hypokinesia (the role of training)]. AB - The male Wistar rats were used to study an effect of preliminary antiorthostatic training on the systemic and regional hemodynamics during 24-hour head down tilting (HDT). It is indicated that the main parameters of the systemic hemodynamics (arterial blood pressure, heart rate, central venous pressure, total peripheric resistance, systemic veins) in trained animals were changed to a lesser extent as opposed to the controls. The dynamics of the mean pressure of blood filling--a parameter responsible for the state of systemic veins of the body--was group different. The blood flow changes in the organs and tissues were tended to be the same, however these changes were less severe in the trained rats. Thus pretraining of the rats, not changing the general trend of the shifts in the recorded values, decreases the severity of their variations. PMID- 1296844 TI - [The combined action of head-down tilt hypodynamia and gamma irradiation on higher nervous activity in rats]. AB - The paper deals with a combined effect of 30-day HDT and gamma radiation at a dose of 3 Gy on the higher nervous activity of the experimental rats. In the rats, the immobilization and isolation stresses induced by HDT are found to cause the development of pathologic aggressive reaction with the disorder of a species typical pattern of an aggressive act and long-term change in animal social relations. The 30-day HDT disturbs the process of forming the motor-drinking differentiated conditioned reflex coming to a reduction of internal inhibition, generalization and sluggishness of a stimulation process. Functionally, these processes are reflected by a behavioral pattern shifting to stable stereotype impeding the formation of differentiated inhibition. Against HDT the unidirectional gamma radiation exposure increases this effect. In some cases, it leads to blocking the adaptational processes showing in the development of neurotic responses or deep, beyond the limits, inhibition. PMID- 1296845 TI - [The early andrological effects in rats under the combined action of irradiation and vibration]. PMID- 1296846 TI - [The use of electroanalgesia to restore the work capacity of aquanauts]. PMID- 1296847 TI - [Normal interlabyrinthine otolithic asymmetry and following exposure to a changed G force]. PMID- 1296848 TI - [An increase in the resistance to cold exposure in laboratory animals under the influence of polypeptides from the bursa of Fabricius]. PMID- 1296849 TI - [The ecological-morphological characteristics of the growth and distribution of cultures of single-cell organisms in a gravitational field]. AB - The paper analyses and summarizes the experimental results obtained by the authors and data accumulated in the literature during recent years in order to reveal the general regularities of the growth, distribution and behavioral parameters of the cells under conditions of reduced gravity ranged from 10(-5) to 5 g. It is indicated that an intensity of gravity effect on these parameters of unicellular organisms depends greatly on the environments, types of cells and their metabolic levels. The effects of changed gravity at the cellular level are the result of shifting the primary physiological characteristics and physicochemical parameters of the culture and cell environments as an integrated biological system. PMID- 1296850 TI - [Ultrastructure of the myocardium in the calcium channel blocker withdrawal syndrome]. AB - Changes in the ultrastructure of rat myocardial cells were investigated after withdrawal of therapy with the calcium entry blockers diltiazem, nifedipine, and verapamil. Two hours after the last administration the ultrastructure was without significant changes in comparison to the control group. However the incidence of contracture bands, dehiscence of intercalated discs and lesions of mitochondria observed 30 hours after therapy withdrawal demonstrated serious damage of myocardial tissue. The recorded changes, practically identical with changes associated with the calcium paradox, were the consequence of withdrawal of calcium entry blocker therapy. The reported morphological changes reflected biochemical and functional changes characteristic of the calcium entry blocker withdrawal syndrome. PMID- 1296851 TI - [The effect increased choline levels on the synthesis and release of acetylcholine in heart atria in white rats]. AB - The paper addresses the problem of (1) the relationship of choline in extracellular fluid and acetylcholine (ACh) synthesis in chambers of the heart of white rats, and (2) the possibility of physiological involvement of this ACh in the control of cardiac activity. Within 60 min after s.c. administration of choline in the dose of 300 mg/kg body weight the ACh content rose to 136% of the control value in isolated heart chambers and after administration of 400 mg/kg body weight to 159% of the control value. Increased ACh synthesis failed to affect the heart rate, nor did it increase the tonic effect of vagus innervation of the heart. Excessive ACh could however be released by electric transmural stimulation of isolated heart chambers as well as by potassium depolarization. The release depended on the presence of calcium ions. The obtained results demonstrate that an increase in the level of choline in extracellular fluid results in increased ACh synthesis in nerve terminals. Enhanced release of this ACh is a precondition for high choline levels to induce an increase in parasympathetic control of cardiac function. PMID- 1296852 TI - [Familial supravalvular aortic stenosis]. AB - By means of two dimensional echocardiography supravalvular aortic stenosis was diagnosed in two siblings and their cousin. Autosomal dominant transmission with incomplete penetrance or even non-penetrance is assumed to be involved. Somatic stigmatization, typical for Williams' syndrome, failed to be present in the affected children. The reported family provides further evidence that familial supravalvular aortic stenosis and Williams' syndrome are two distinct clinical entities. (Tab. 1, Fig. 3, Ref. 23.) PMID- 1296853 TI - [Isolated arteritis of the central nervous system]. AB - Isolated arteritis of the central nervous system (CNS) is a relatively rare condition. Of the patients treated at our department two presented with characteristic features and eventually the diagnosis of isolated arteritis of the CNS was established. Headaches and relapsing lesions of cerebral nerves were predominant in the clinical picture of the first patient. In agreement with the clinical picture suggesting that small arteries were affected, the angiographic (AG) finding was negative and the diagnosis was based mainly on the positive effect of immunosuppressive treatment. The second patient with relapsing monofocal brain damage had a typical AG finding and a positive response to the treatment. The clinical picture of isolated arteritis of the CNS can be rather varied, with headaches and different neurological features being predominant. Both AG and bioptic examinations may prove negative. Positive response to immunosuppressive treatment is to be considered a characteristic feature of the disease. (Fig. 3, Ref. 11.) PMID- 1296854 TI - [Precancerous and malignant tumors of the uterine cervix]. AB - Bioptic findings recorded in 366 women with lesions of the endocervix and exocervix were analyzed in a retrospective study covering the years 1988 to 1990. The series represented 24.5% of the total number of 1495 gynecological precancerous and tumorous changes. Severe dysplastic changes and malignant tumors of the endocervix were seen in 31 patients (19.4%). Concurrence of endocervical and exocervical lesions was recorded in 66 patients (18.0%). In the studied series 35% of the women were below the age of 40 years. Signs of koilocystic dysplasia were recorded in 72 women (37%) with precancerous and tumorous lesions. (Fig. 4, Ref. 15.) PMID- 1296855 TI - [Biological effects of selenium]. AB - The role of selenium concerning its biological effects particularly in relation to cardiovascular and tumor diseases has been in the focus of intensive studies. Selenium is a constituent part of the enzyme glutathion peroxidase (E.C.1.11.1.9) which catalyzes the conversion of hydrogen peroxide and organic hydroperoxides into water and corresponding alcohols. A review of epidemiological studies is presented focusing predominantly on countries where a low concentration of selenium in blood serum was found. The role of selenium in the etiology of cardiovascular diseases may probably be accounted for by its protective effect as it prevents platelet aggregation and protects the arterial endothelium from being damaged by lipid peroxides. The results of experimental studies, carried out in research institutes in many parts of the world, suggest that coordinated supplementation of food with selenium may reduce the risk of cancer and moreover, the effect of selenium can be modified by other dietary factors, such as vitamin A and E. (Fig. 2, Ref. 29.) PMID- 1296856 TI - Fuel selection and the production of ammonium by the kidney: studies using insulin. AB - The purpose of this study was to explore the interrelations among energy turnover, the selection of fuels, and the production of ammonium (NH4+) in the kidney during chronic metabolic acidosis. Experiments were carried out in dogs because of the extensive background literature in this species. The specific question addressed was, will a diminished rate of oxidation of fatty acids in the kidney permit the rate of extraction of glutamine and the production of NH4+ to rise? Chronic metabolic acidosis was induced by the ingestion of NH4Cl for 5 days to stimulate the rate of production of NH4+. Insulin was administered to diminish the delivery of fatty acids to the kidney. The concentration of fatty acids in plasma fell from 350 +/- 104 to 188 +/- 45 microM, yet there was no significant increase in the rates of production of NH4+, consumption of oxygen, or extraction of glutamine after insulin. Notwithstanding, there was a significant rise in the rate of extraction of lactate by the kidney when expressed per 100-mL glomerular filtration rate. Because there was a significant decline in the level of glutamine in plasma (512 +/- 76 to 359 +/- 42 microM) 1 h after giving insulin, a second series of experiments was carried out. When glutamine was infused after the insulin period, there was no longer a fall in the concentration of this metabolite. Notwithstanding, the rates of extraction of glutamine and production of NH4+ were not higher in the presence of insulin. These data suggest that the rate of oxidation of fatty acids did not limit the rate of oxidation of glutamine in the kidneys of fed dogs with chronic metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1296857 TI - Effects of N6-endonorbornan-2-yl-9-methyladenine, N0861, on negative chronotropic and vasodilatory actions of adenosine in the canine heart in vivo. AB - The pharmacology of N6-endonorbornan-2-yl-9-methyladenine (N0861), a new selective antagonist of adenosine at the A1 adenosine receptor subtype (A1-AdoR), was studied in vivo using a canine model. First, the pharmacokinetics of N0861 were determined in anesthetized dogs. The time-dependent decay of plasma levels of N0861 fitted a two-compartment polyexponential model with alpha-phase t1/2 = 3.80 min and beta-phase t1/2 = 80.55 min. Secondly, the effect of N0861 on the negative chronotropic and vasodilatory actions of adenosine in the canine heart were determined. N0861 attenuated the negative chronotropic action of adenosine (1-6 mumol/kg; rapid bolus into the right atrium) on sinus node pacemaker activity in a dose-dependent manner (pA2 = 4.23). For example, the maximal prolongation of sinus cycle length induced by 6 mumol/kg adenosine was 82 +/- 13% under baseline conditions and 57 +/- 10, 34 +/- 5 and 34 +/- 6% during infusion of N0861 at incremental rates leading to plasma levels of 7.75 +/- 1.02, 14.15 +/ 0.87, and 19.71 +/- 1.83 micrograms/mL, respectively. In contrast, N0861 did not inhibit but had a tendency to potentiate the vasodilatory action of adenosine (thought to be mediated by the A2 adenosine receptor subtype (A2-AdoR)) on the left anterior descending and circumflex coronary arteries. These data indicate that two different receptors, similar to the typical A1-AdoR and A2-AdoR, mediate the electrophysiologic and vasodilatory actions of adenosine in the canine heart, respectively, and that N0861 is a selective antagonist of adenosine at A1-AdoR in the canine heart in vivo. PMID- 1296858 TI - Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder. AB - The relationship between vesical mechanoreceptor field dimensions and afferent nerve activity recorded in pelvic plexus nerve filaments was examined in chloralose-anesthetized cats. Orthogonal receptor field dimensions were monitored with piezoelectric ultrasonic crystals. Reflexly generated bladder contractile activity made measurements difficult, therefore data were collected from cats subjected to actual sacral rhizotomy. Afferent activity was episodic and was initiated at different pressure and receptor field dimension thresholds. Maximum afferent activity did not correlate with maximum volume or pressure. Furthermore, activity was not linearly related to intravesical pressure, receptor field dimensions, or calculated wall tension. Pressure-length hysteresis of the receptor fields occurred. The responses of identified afferent units and their associated receptor field dimensions to brief contractions elicited by the ganglion stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (2.5-20 micrograms i.a.), studied under constant volume or constant pressure conditions, are compatible with bladder mechanoreceptors behaving as tension receptors. Because activity generated by bladder mechanoreceptors did not correlate in a simple fashion with intravesical pressure or receptor field dimensions, it is concluded that such receptors are influenced by the viscoelastic properties of the bladder wall. Furthermore, as a result of the heterogeneity of the bladder wall, receptor field tension appears to offer a more precise relationship with the activity of bladder wall mechanoreceptors than does intravesical pressure. PMID- 1296859 TI - Effects of deoxycorticosterone acetate on glucose metabolism in nondiabetic and streptozotocin-diabetic rats. AB - A previous study in our laboratory showed that streptozotocin (STZ) induced diabetic, deoxycorticosterone acetate (DOCA) induced hypertensive rats exhibited significantly lower levels of plasma glucose than did normotensive diabetic animals. The present experiments further investigate the effects of DOCA treatment on fasting levels of plasma glucose and insulin and on their changes after oral glucose challenge in nondiabetic and STZ-diabetic rats. It was found that, in nondiabetic rats, DOCA-induced hypertension was associated with normal glucose levels and glucose tolerance but with significantly lower levels of plasma insulin. DOCA-treated diabetic animals showed significantly lower levels of plasma glucose, but their plasma insulin concentrations were not significantly different from those of the DOCA vehicle treated diabetic rats. DOCA-treated diabetic rats also had significantly higher plasma levels of cholesterol and triglycerides. It is suggested that DOCA may have a direct or indirect action on the assimilation, production, or utilization of glucose, perhaps leading to an improvement in insulin sensitivity and subsequently a decrease in insulin secretion. PMID- 1296860 TI - Glucose uptake by adipocytes of obese rats: effect of one bout of acute exercise. AB - The effect of one bout of acute exercise on impaired glucose metabolism was studied in obese (480 +/- 20 g), untrained rats, at rest (n = 10) and after 60 min of swimming (n = 5). Using the euglycemic, hyperinsulinemic (10 mU.kg-1 x min 1) clamp, glucose clearance rate increased from 7.6 +/- 0.9 at rest to 9.7 +/- 0.5 mL.kg-1 x min-1 after exercise (p < 0.05). Glucose (3-O-[14C]methylglucose) transport (GT) into epididymal adipocytes were incubated with or without insulin. In the absence of insulin, GT was 0.13 +/- 0.02 and 0.26 +/- 0.07 fmol.cell-1 x min-1 at rest and after exercise, respectively. In the presence of insulin (25 1000 microU.mL-1) GT increased at rest from 0.97 +/- 0.08 to 1.13 +/- 0.07 fmol.cell-1 x min-1, and after exercise from 1.35 +/- 0.05 to 1.87 +/- 0.11 fmol.cell-1 x min-1. GT was significantly higher after exercise compared with rest (p < 0.004). At rest, maximal insulin effect was achieved at 100 microU.mL 1, whereas with exercise, GT increased gradually with the insulin dosage. The following may be concluded: (i) the biological effect of insulin is amplified in obese rats by one bout of exercise and (ii) exercise affects GT into enlarged adipocytes by enhancing tissue responsiveness to insulin and by a cellular mechanism unrelated to the insulin action. PMID- 1296861 TI - Is accelerated oxidation of lactate required for dichloroacetate to lower the level of lactate in blood? AB - We examined mechanisms by which dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), led to a decrease in the concentration of lactate in blood in a unique "metabolic setting," where the concentration of lactate in blood was 5.4 +/- 0.5 mmol/L. Elevated levels of lactate were induced in anaesthetized rabbits by the administration of a large dose of insulin. The rate of consumption of oxygen was 1.2 +/- 0.1 mmol/min, the respiratory quotient was close to unity, and close to half of the PDH was in its active form; therefore, virtually all ATP synthesis should require flux through PDH. Hence, we predicted that DCA should not cause a significant decrease in the concentration of lactate in blood in this model. In contrast, if DCA was effective, new insights could be obtained into its mechanisms of action, at least in this setting. During steady-state hyperlactatemia, DCA was given as its sodium salt, 2 mmol/kg (n = 10); a control group (n = 5) received equimolar NaCl. Forty minutes later, the level of lactate in blood in the DCA group was 1.3 +/- 0.2 mmol/L, significantly lower than in the NaCl group (4.2 +/- 0.6 mmol/L). To determine the organ(s) responsible for removing lactate, arteriovenous differences were measured in organs drained by the jugular, femoral, and hepatic veins. There was no net uptake of lactate in these drainage beds after DCA was administered. From a quantitative analysis of the rate of removal of lactate and the rate of consumption of oxygen, it seems unlikely that the majority of the decrease in lactate could be directly attributed to an increase in its oxidation. PMID- 1296862 TI - Motilin and the postprandial motility of the antrum. AB - This study was designed to establish whether the rise in plasma motilin observed after a meal in humans can influence the postprandial motor activity of the antrum. Antroduodenal postprandial motility profiles and indices obtained from 5 controls and 5 subjects infused with exogenous synthetic motilin (0.1 microgram.kg-1) or with the motilin receptor agonist erythromycin lactobionate (200 mg) were compared. Motilin infusion increased plasma motilin concentrations about 5 times above the physiological range but failed to modify the normal postprandial contractile response. On the other hand, in 4 of the 5 subjects, erythromycin induced an intense motor response that mimicked phase III of the migrating motor complex. Our study demonstrates that, during the postprandial period, motilin antral receptors can be stimulated only with doses of motilin exceeding the physiological plasma concentrations, and that the motor effect obtained did not mimic the usual postprandial motility pattern. Our results, therefore, do not support the proposal that the postprandial motility of the antrum is regulated by the plasma levels of motilin. PMID- 1296863 TI - Incidence of multinucleated and polyploid aortic smooth muscle cells cultured from different age groups of spontaneously hypertensive rats. AB - Cell size and incidence of multinucleated, polyploid cells in cultured aortic smooth muscle cells from different age groups of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared. Smooth muscle cells from SHR were generally larger than those from WKY, and the percentage of multinucleated smooth muscle cells was always higher in SHR than WKY in the three age groups of rats studied (3-4, 10-12, and 28-30 weeks). In smooth muscle cells from the 3- to 4-week group, there was a positive correlation between cell diameter and the percentage of multinucleated smooth muscle cells. Microdensitometric measurements also showed that the incidence of polyploid smooth muscle cells was always higher in SHR than WKY in the three age groups. There was a positive correlation between DNA density and nuclear area measurements in all the age groups of SHR and WKY. We conclude that cultured aortic smooth muscle cells from different age groups of SHR and WKY contained heterogeneous populations of cells and that, under our culture conditions, the polyploidy of the smooth muscle cells found in vivo was maintained in the SHR and WKY. PMID- 1296864 TI - Absence of hepatic p-nitrophenol UDP-glucuronosyltransferase induction by spironolactone in male rats: possible involvement of testosterone. AB - This study was performed to determine whether the lack of spironolactone induction of hepatic p-nitrophenol UDP-glucuronosyltransferase in male rats could be attributed to a presumed interaction between spironolactone and testosterone. The effect of spironolactone was evaluated in four experimental groups: normal females, normal males, castrated males, and castrated males that received testosterone. Enzyme activity was measured in native microsomes and in microsomes activated with UDP-N-acetylglucosamine or Triton X-100. When the nucleotide was included in the incubations, it was observed that enzyme activity in castrated male rats decreased to values approaching those obtained in normal females. Treatment of castrated animals with testosterone enhanced enzyme activity so that no significant difference existed between this group and normal males. This suggests that testosterone may act as an endogenous inducer of hepatic p nitrophenol glucuronidation. It was also found that only females and castrated males showed an increase in enzyme activity in response to spironolactone treatment. Thus, the absence of an additive effect of endogenous or exogenous testosterone and spironolactone on UDP-glucuronosyltransferase activity suggests that these compounds could share a common induction mechanism, which appears to reach its maximal capacity in male rats. Possible explanations of this observation are discussed. From the analysis of enzyme activity in native and Triton X-100 activated microsomes, it can be postulated that spironolactone enzyme induction in female and castrated male rats could be attributed to an enhancement in the transferase synthesis rather than to an alteration of the membrane environment. PMID- 1296865 TI - Low concentrations of hydrogen sulphide alter monoamine levels in the developing rat central nervous system. AB - The central nervous system is one of the primary target organs for hydrogen sulphide (H2S) toxicity; however, there are limited data on the neurotoxic effects of low-dose chronic exposure on the developing nervous system. Levels of serotonin and norepinephrine in the developing rat cerebellum and frontal cortex were determined following chronic exposure to 20 and 75 ppm H2S during perinatal development. Both monoamines were altered in rats exposed to 75 ppm H2S compared with controls; serotonin levels were significantly increased at days 14 and 21 postnatal in both brain regions, and norepinephrine levels were significantly increased at days 7, 14, and 21 postnatal in cerebellum and at day 21 in the frontal cortex. Exposure to 20 ppm H2S significantly increased the levels of serotonin in the frontal cortex at day 21, whereas levels of norepinephrine were significantly reduced in the frontal cortex at days 14 and 21, and at day 14 in the cerebellum. PMID- 1296866 TI - Reduced sensitivity to dexamethasone of pancreatic islets from obese (fa/fa) rats. AB - The direct effects of dexamethasone exposure on insulin secretion from islets of fa/fa rats and their lean littermates (Fa/?) were compared. After 72 h culture in 1 nM dexamethasone, glucose (27.5 mM)-stimulated insulin secretion over 90 min from islets of lean rats was significantly decreased compared with islets cultured without dexamethasone (12.9 +/- 1.4 vs. 5.7 +/- 1.0% of total islet content, p < 0.05). Higher doses of dexamethasone for 24-48 h culture produced similar effects. For islets of fa/fa rats, the minimum inhibitory concentration of dexamethasone was 10-fold higher, and islets required at least 48 h exposure for inhibitory effects to be observed. Dexamethasone also decreased the insulin response by islets to glybenclamide, indicating that dexamethasone effects were not specific to glucose transport or metabolism. The results suggest that islets of fa/fa rats may be less sensitive to direct inhibitory effects of glucocorticoids on glucose-stimulated insulin release than islets of lean animals. PMID- 1296867 TI - Effects of chronic hypoxia on the whole-body insulin action in rats. AB - The effect of chronic hypoxia on the whole-body insulin action in rats was investigated. Rats were kept in a hypobaric hypoxia chamber maintained at a simulated altitude of 4000 m for 10 weeks. At the end of the experimental period, the mean body weight of the hypoxic rats was significantly lower than that of the control rats. The muscle weight to body ratio of the quadriceps muscle in hypoxic rats was larger than that in control rats, but those of the gastrocnemius, soleus, and extensor digitorum longus muscles did not differ between the control and hypoxic rats. On the other hand, the epididymal fat pads of hypoxic rats were markedly smaller than those of the control rats. The results of a euglycemic clamp experiment with infusions of 14 and 3.6 mU insulin.kg-1.min-1 indicated that the steady-state glucose infusion rate was not statistically different between hypoxic and control rats. It is suggested that chronic hypoxia did not influence the whole-body insulin action on glucose transport activity. PMID- 1296868 TI - [The process of adaptation to illness in persons with acquired immunodeficiency syndrome]. AB - This study was conducted to describe the adaptation process to illness. The study subjects were 50 AIDS patients. The study variables and tools of measurement were chosen according to the Psychosocial Adaptation Model of Craig and Edwards (1983). It was found that throughout the disease process an appraisal-reappraisal of the situation is continuous. The sick person constantly evaluated the severity of his losses and the availability of the coping strategies at his disposal. The study results demonstrated that persons afflicted with AIDS suffer considerable amount of physical and psychosocial prejudice. It was apparent that the patients who suffered severe physical, psychological and social losses used avoidance strategies. Those preoccupied with the physical losses had a tendency to use the strategy of emotional discharge. Otherwise the study subjects sought information rather than emotional discharge to come to terms with their losses. In addition, the use of logical analysis strategies was associated with an increase in psychological well-being. In contrast, the strategy of avoidance was associated with a decrease in well-being. Finally, the subjects with the advanced disease experienced more severe losses of a social nature and made less use of logical analysis strategies than did subjects in the early phases of the disease. PMID- 1296869 TI - Conceptual issues related to measurement in family research. PMID- 1296870 TI - Faculty practice competencies: nurse educators' perceptions. PMID- 1296871 TI - Preceptor selection criteria in Canadian basic baccalaureate schools of nursing- a survey. PMID- 1296872 TI - Life on hold: the experience of the support person involved in a lung transplant program. PMID- 1296873 TI - Do we really need an algorithm for the diagnostic work-up of a patient with suspected pulmonary embolism? PMID- 1296874 TI - [Heart failure in the population: prevalence data]. AB - We report on the prevalence of chronic heart failure (CHF) in a random sample of a population (aged 20-64 years) from the Veneto region in northern Italy. The relationship between CHF and hypertension and obesity was also investigated. These data were collected during an international research project coordinated by the World Health Organization. The overall prevalence of CHF was 2.0% both in the male and female population. The prevalence of CHF increased significantly with age and was positively correlated with body mass index in both sexes. Patients with borderline hypertension showed a 3.5-fold increased prevalence of CHF. The prevalence of CHF was 4.9-fold higher in hypertensive than in the normotensive subjects. Patients treated with hypotensive drugs had a significantly higher prevalence of CHF than untreated patients. PMID- 1296875 TI - [The circadian rhythm of plasma vasoactive intestinal peptide, atrial natriuretic peptide, renin activity, aldosterone and cortisol in heart transplantation. The effects of immunosuppressive therapy]. AB - Vasoactive intestinal peptide (VIP) is released both by neural endings and lymphocytes. Aim of our investigation was to study the effects of immunosuppressive therapy on VIP plasma concentrations. The research has been performed on 10 heart transplanted patients assuming cyclosporine (CYCL) and prednisone (PRED). The circulating T lymphocyte subsets, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) have been also assayed. Blood pressure (BP) and heart rate (HR) have been monitored over a 24-hour period to detect whether circulating VIP in heart transplanted patients is influenced by pharmacologically-induced interactions. Seriate samplings along the 24-hour span have been performed. Mean values of ANP, PRA and PA were increased, while VIP, PC and T lymphocyte subsets were decreased in heart transplanted patients as compared to clinically healthy subjects. ANOVA and Cosinor analysis showed, respectively, a statistically significant 24-hour variability and circadian rhythm for all the investigated variables only in normal subjects. BP and HR circadian rhythm in heart transplanted patients suggest that the adrenergic activity regulating the cardiovascular system is restored. This finding argues that the reduction in VIP plasma concentrations is likely due to the decreased lymphocyte production secondary to immunosuppressive therapy, or can also be ascribed to the inhibiting action of high circulating levels of ANP. PMID- 1296876 TI - Prolonged asymptomatic catheter-induced left and right coronary artery spasm resistant to high dose of intracoronary nitroglycerin. AB - A 58-year-old woman, referred to our hospital to undergo invasive assessment of mitral valve stenosis, demonstrated prolonged asymptomatic catheter-induced left anterior descending and right coronary artery spasm during coronary arteriography. Coronary spasms were not associated with ECG and arterial blood pressure changes. Intracoronary injection of nitroglycerin (300 and 600 micrograms bolus) did not resolve coronary spasm. Coronary angiography, repeated 24 hours later using the same procedure and materials, did not show any evidence of coronary artery spasm. The present clinical case is interesting for 3 reasons. First, the presence of prolonged proximal double-vessel coronary spasm not associated with symptoms or signs of acute myocardial ischemia; second, the incapacity of high dose of intracoronary nitroglycerin to resolve the coronary spasm; third, the dramatic changes in the sensitivity of coronary artery to mechanical stimulation in different days. PMID- 1296877 TI - [The effect of superoxide dismutase and catalase on the delayed toxicity of doxorubicin]. AB - The production of oxygen-free radicals has been proposed as a determinant of the delayed toxicity of doxorubicin. The aim of the present investigation was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) and catalase (CAT) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD or CAT were administered intravenously at the dose of 10000 U/kg 2 min before and 30 min after each DXR administration. Cardiac toxicity was monitored by means of electrocardiography (QaT interval) and by light and electron microscopy evaluation of left ventricle fragments. DXR treated rats showed, in comparison with control animals, a decrease of body weight gain, a progressive and irreversible prolongation of QaT and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain and QaT prolongation. Moreover, morphologic lesions were significantly reduced in rats receiving DXR + SOD. On the contrary, CAT seems to be completely devoid of protective effect. PMID- 1296878 TI - [Variations in the purine metabolism of the reperfused heart]. AB - Isolated hearts were subjected to 30 min of aerobic perfusion followed by 10 min of global normothermic ischemia and 40 min of reperfusion. We determined the release of purine catabolites (adenosine, inosine, hypoxanthine, xanthine, uric acid) and the incorporation of exogenous 3H-adenosine and 14C-hypoxanthine into cellular nucleotides. Ischemia-reperfusion produced remarkable reduction in the release of purine catabolites, with no significant variation in the incorporation of adenosine and hypoxanthine. PMID- 1296879 TI - [L-propionylcarnitine taurine amide induces the metabolic recovery of the isolated postischemic rat heart]. AB - The effect of reperfusion with L-propionyl-carnitine-taurinammide 1 mM was evaluated on the metabolic recovery of the isolated postischemic rat heart. Data referring to the tissue concentration of the high-energy phosphates, oxypurines, nucleosides, nicotinic coenzymes, lactate and pyruvate indicate that L-propionyl carnitine-taurinammide significantly improves the metabolism of the reperfused myocardium. In particular, ATP, creatinphosphate, GTP, sum of adenine nucleotides and the energy charge resulted 1.80, 1.83, 3.47, 1.47 and 1.20 times higher respectively than the corresponding values recorded in control reperfused heart (p < 0.01 all). These data, out of supplying the necessary biochemical support to the beneficial effects of L-propionyl-carnitine-taurinammide on hemodynamics obtained in previous studies, suggest that L-propionyl-carnitine-taurinammide might represent a useful tool for the pharmacological treatment of myocardial infarction. PMID- 1296880 TI - [Coenzyme Q9 biosynthesis in the aging myocardium after ischemia and reperfusion]. AB - The purpose of the present study was to evaluate the biosynthesis of coenzyme Q9 (CoQ9) in isolated and perfused young (6 months) and aged (24 months) rat hearts, either under aerobic perfusion condition or during postischemic reperfusion. The young and aged hearts have been divided into 2 groups: Group A, aerobic perfusion for 60 min with recirculating Krebs-Henseleit solution, containing 0.8 microM p OH-[U-14C]benzoate plus 2.5 mM mevalonlactone; Group B, severe ischemic perfusion for 30 min, followed by 60 min of reperfusion under the same experimental condition of Group A. At the end of the reperfusion the mitochondrial content of CoQ9 was lower in young than aged rat hearts (p < 0.01). In Group A the incorporation of the labeled precursor into mitochondrial CoQ9 was greater in the hearts of aged than young rats (p < 0.01); on the contrary, in Group B this incorporation was significantly reduced in aged than in young rats (p < 0.05). Thus, it is possible that, in the aged rat heart, the higher activity of CoQ9 biosynthesis is related to an elevated turnover of the coenzyme due to the aging process; moreover, this activity is partially reduced by an ischemic-reperfusion stress. PMID- 1296881 TI - [Heterotopic heart transplantation in the rat: an experimental method for evaluating myocardial protection]. AB - This research represents the first part of a project finalized to prolong the ischemic time of the explanted heart. Our experimental model utilizes rat hearts heterotopically transplanted into the abdomen of a recipient: a denervated heart but perfused by blood as to permit a good evaluation of the reperfusion damage. We used 3 different types of cardioplegic solutions to achieve cardiac arrest: the first of the intracellular fluid type, the second of the extracellular type and the third one as a standard cardioplegic solution supplemented by Ca++ antagonist. Cold saline 4 degrees C was used as control. Histological patterns, birefringence index and intracellular content of high energy phosphates were evaluated. Specimens were taken after 1 hour of ischemic time and after 1 hour of reperfusion. Early results show that administration of cardioplegic solution maintains birefringence index and preserve high energy phosphates: among the 3 different types of solution the intracellular type seems to achieve better results although the number of experiments is too small to show any statistical significance. These data show that this model is appropriate to test cardioplegic solutions and their effectiveness. PMID- 1296882 TI - [The effect of peripheral reflections on the left ventricle]. AB - In order to evaluate the effect of modifications in reflections timing on the ventricular performance, 10 isolated rabbit hearts were connected to rubber tubes of different lengths (0.5, 0.8, 1.0, 2.5 m) with terminal stopper and 2 cylindric small tubes as constant hydraulic resistance. The terminal connection produced wide reflections which returned to the ventricle in early, mid, late systole and in the diastolic phase (2.5 m). Ventricular and aortic pressure, and aortic flow were continuously recorded, sampled and stored on a personal computer. Instantaneous and total systolic ventricular work and stroke volume were calculated using an automatic procedure. Mean coronary perfusion pressure was calculated as difference between aortic and ventricular pressure in diastolic phase. The results demonstrate an important modification of the ventricular performance related to the anticipation of the reflected pulse. The anticipation produces a decrease in the stroke volume (-14.5%), a decrease in the external work of the ventricle (-21%) and a decrease in mean coronary perfusion pressure ( 28%). The first two parameters describe the performance of the pump with respect to the load, and the third evaluates the perfusion of the pump itself. Reported to the clinical situation, these results demonstrate that an increased stiffness of the aorta has a double negative effect, a decrease in cardiac output and in external ventricular work, and moreover a decrease in coronary pressure, which produces a reduction of coronary flow. PMID- 1296883 TI - [A noninvasive assessment of the gain in baroceptor control of the heart rate in man]. AB - In this study we addressed the problem of the noninvasive evaluation of the overall gain of baroreceptor control of heart period. We studied a population of healthy controls (n = 49, age 30 +/- 2 years, systolic arterial pressure [by Finapres] 114 +/- 1 mmHg) and a group of mild hypertensive subjects (n = 14, age 51 +/- 2 years, systolic arterial pressure 151 +/- 5 mmHg). Subjects were studied at rest both in absence and in presence of chronic beta-adrenergic receptor blockade (atenolol: controls 50 mg po oid x 4 days; hypertensives 100 mg po oid x 2 weeks). Spectral analysis of RR interval and of systolic arterial pressure variabilities provided noninvasive markers of autonomic control of the SA node and of the vasculature. The index alpha, obtained from bivariate cross spectral and spectral analysis provided a quantitative assessment of the closed loop gain of baroreceptor control of the heart period. The index alpha resulted more elevated in the normotensive than in the hypertensive group. Additionally it appeared significantly increased at the end of the treatment with the beta adrenergic blocking drug atenolol. Furthermore, alpha appeared significantly and negatively correlated with age, systolic arterial pressure and, although weakly, with low frequency; it was positively correlated with the average RR interval. In conclusion, this study suggested an important link between the average level of sympathetic activity and baroreceptor control of heart rate in normotensive and mild hypertensive subjects. The clinical importance of this sympathetic modulation of the gain of the heart period/arterial pressure relationship can now be assessed with this noninvasive approach. PMID- 1296884 TI - [The relationship between anomalies in the autonomous nervous system and left ventricular dysfunction in patients with hypertrophic cardiomyopathy]. AB - This study was undertaken to assess autonomic nervous system (ANS) activity and its relation to left ventricular function in 40 patients (mean age: 41 +/- 17 years) with hypertrophic cardiomyopathy (HC), in sinus rhythm, off-drugs. Patients were grouped according to the results of radionuclide angiography: 26 had an ejection fraction > 50% (Group A), whereas 14 had an ejection fraction < or = 50% (Group B). Evaluation of parasympathetic activity showed abnormalities in: heart rate (HR) response during Valsalva (< or = 1.1) in 2 Group A (8%) and 12 Group B (86%) patients (p < 0.001); HR variability during deep breathing (< or = 10 b/min) in 2 Group A (8%) and 14 Group B (100%) patients (p < 0.001); immediate HR response to standing (30:15 < or = 1.0) in 2 Group A (8%) and 6 Group B (43%) patients (p < 0.025). Assessment of sympathetic activity showed abnormalities in: systolic blood pressure fall to standing (> 20 mmHg) in 2 Group B (14%) patients only (NS); diastolic blood pressure response to handgrip (< 10 mmHg) in 4 Group B (29%) patients only (p < 0.025). Thus, in HC: impaired parasympathetic control is common in those patients showing left ventricular dysfunction; concurrent sympathetic abnormality may also occur in this subgroup of patients; ANS dysfunction seems to be merely an epiphenomenon which marks the severity of left ventricular derangement. PMID- 1296885 TI - 'When love and skill work together, expect a masterpiece'. PMID- 1296886 TI - Baby food exchanges and meal planning for the infant with diabetes. PMID- 1296887 TI - Meal planning approaches: practical application. PMID- 1296888 TI - A review of recent events in the history of diabetes nutritional care. AB - This paper provides an historical documentation and discussion of events that have influenced diabetes nutritional management in recent years. Many factors have shaped the nutrition care that persons with diabetes receive today. Nutrition science research is part of the history, as are myriad discoveries, research, advanced technologies, and evolving health care systems. This review of the past four decades will contribute a perspective of how we have gotten to where we are today. PMID- 1296889 TI - Perceived and actual knowledge of diet by individuals with non-insulin-dependent diabetes. AB - A study was conducted to investigate both the perceived and actual knowledge of diet by 101 individuals with non-insulin-dependent diabetes mellitus (NIDDM). A survey instrument was developed containing three sections: perceptions of diet knowledge, demonstrated knowledge of diet, and demographic information. Perceived and actual knowledge of diet in the study group were compared with the following variables: years of education, types of diabetes regimen, participation in care, recency of dietary instruction, understanding of diet, and levels of self blood glucose monitoring (SBGM). Analysis indicated significant differences for knowledge and levels of education, perceptions and knowledge and recency of instruction, perceptions and knowledge and understanding of diet, and perceptions and self blood glucose monitoring. A positive linear relationship was noted between perceptions and actual knowledge of the diabetic diet. PMID- 1296890 TI - Management of obesity in diabetes mellitus. AB - A primary goal of treatment in obese individuals with NIDDM is weight loss and maintenance. Obesity is a precipitating factor for the development of NIDDM in individuals who are genetically at risk. A variety of weight-loss regimens are available to match the specific needs and lifestyles of individuals. Hypocaloric high-fiber diets have been found to be effective in achieving weight loss, as well as aiding in glycemic and lipid control. Very low calorie diets, administered under medical supervision, are useful for obese NIDDM patients with 18-55 kilograms of weight to lose. Lifestyle education appears to be an important element of any successful weight loss program. PMID- 1296891 TI - Diabetes quality assurance checklist: assessment of inter-rater and intra-rater reliability. AB - The Diabetes Quality Assurance (DQA) Checklist was developed to measure adherence to standards of diabetes care. Two raters simultaneously scored a convenience sample of 23 charts of patients with diabetes. These raters scored each chart again 5-7 weeks later. Data obtained were used to assess inter-rater and intra rater reliability. Inter-rater reliability was estimated for basic assessment at Time 1 (r = 0.94, 95% CI 0.86-0.97) and at Time 2 (r = 0.91, 95% CI 0.81-0.96); and for high-risk assessment at Time 1 (r = 0.88, 95% CI 0.73-0.95). Intra-rater reliability for the basic assessment was estimated for Reviewer 1 (r = 0.84, 95% CI 0.65-0.93) and for Reviewer 2 (r = 0.75, 95% CI 0.49-0.89); the high-risk estimate for Review 1 was 0.60 (95% CI 0.25-0.81) and for Reviewer 2 0.97 (95% CI 0.94-0.99). The DQA Checklist is useful for monitoring and assessing diabetes care. PMID- 1296892 TI - A regional diabetes nutrition education program: its effect on knowledge and eating behavior. AB - The effect of a nutrition education program on knowledge and self-care behavior in a group of individuals with diabetes was evaluated. The nutrition education program was developed using outlines and knowledge tests produced by the University of Michigan Diabetes Research and Training Center. The program, sponsored by the American Diabetes Association, Akron Chapter, was presented free of charge to Northeast Ohio area residents. Forty-four individuals participated in the study. Results indicated a statistically significant (p < 0.01) gain in knowledge but no statistically significant change in eating behavior for the sample. However, post-food records indicated that the mean for the percentage of total kcalories (kcals) from protein and fat (ie, 20% and 28%, respectively) were within the American Diabetes Association's recommendations of no more than 20% of kcals from protein and 30% of kcals from fat. In addition, the percentage of kcals from carbohydrate and the recommended total number of kcals improved toward the recommended levels. PMID- 1296893 TI - Vitamin and mineral supplementation in patients with diabetes mellitus. AB - Most patients with diabetes generally do not require routine vitamin and mineral supplementation, just like the rest of the population. However, based on the published medical literature, it would appear that some degree of supplementation with certain vitamins (eg, vitamins C and E) and minerals (eg, magnesium) may be worthwhile and become more commonly recommended in the future. The role of vitamins and minerals in controlling blood glucose levels in the patients with diabetes also is discussed. PMID- 1296894 TI - A simplified approach to documentation of inpatient diabetes education. AB - The DTP/DR is an effective form for planning, implementing, and documenting patient response to diabetes teaching in the inpatient setting. The form improves the consistency of diabetes teaching, the quality of patient care, and the clarity of documentation. Use of the form decreases time required for documentation and facilitates the recording of patient/family responses to teaching. PMID- 1296895 TI - If you have built castles in the air. PMID- 1296896 TI - Sydney meets the ketone challenge--a videodisc for teaching diabetes sick-day management through problem solving. PMID- 1296897 TI - Toward a more physiologic state: the use of human ultralente and the "run and shoot" plan. PMID- 1296898 TI - Foot care: knowledge retention and self-care practices. AB - This study investigated the effectiveness of a "hands-on" foot care teaching/learning approach for adults with diabetes. By random assignment, the control group received a lecture presentation on foot care, while the experimental group participated in a hands-on session on foot care in addition to the lecture presentation. Data concerning the subjects' foot care knowledge and skills, the condition of their feet, and their level of HbA1c were gathered prior to and six months after the foot care educational sessions. No significant increases in knowledge about foot care were observed in the experimental group. The experimental group reported improvements in inspecting and washing their feet on a daily basis, and in care of the toenails. No significant differences were observed in the status of the subjects' feet. The HbA1c readings were significantly improved for both the experimental (t = 4.10, df = 10, p = 0.002) and control (t = 2.25, df = 9, p = 0.051) groups. A hands-on educational session may improve foot care practices temporarily. However, long term effects need to be studied to discern overall improvement of foot care practices and physical status of the feet. PMID- 1296899 TI - Outcomes of hypoglycemia treated by standardized protocol in a community hospital. AB - Hypoglycemia in patients with diabetes was treated by a standardized protocol in a 300-bed community hospital. Patient outcomes were studied retrospectively using data from medical records. Hypoglycemia was defined as a blood glucose level below 80 mg/dL when symptoms were present, or 60 mg/dL regardless of symptoms. Treatment consisted of 20 grams of fast-acting carbohydrate repeated every 15 minutes until the blood glucose level was above 80 mg/dL. The blood glucose level was then rechecked one hour after treatment. Data from 179 episodes were evaluated. In 153 (85%) cases, the blood glucose levels were within the target range (80-200 mg/dL) at the conclusion of treatment. In 135 (76%) cases, the blood glucose level at one hour following treatment was within the same target range. PMID- 1296900 TI - The relationship between health beliefs, adherence, and metabolic control of diabetes. AB - There is evidence that an individual's health beliefs influence performance of health behaviors. The purpose of this study was to determine whether health beliefs in persons with diabetes could be modified during a clinical education program and whether the health beliefs were related to adherence to self-care instructions and metabolic control of diabetes. Health beliefs and HbA1c were measured at baseline in 189 adult outpatients with diabetes. Diabetes educators then attempted to modify health beliefs that were not conducive to positive health behaviors. Following education, some health beliefs were modified in a positive direction. Modest, but statistically significant increases in perceived severity of diabetes, perceived ability to carry out recommended behaviors, and perceived benefits of treatment were observed. Although HbA1c improved significantly in a subgroup of patients, this improvement could not be directly associated with any health belief or with self-reported adherence by the measures used in this study. PMID- 1296902 TI - Guidelines for the student with diabetes: a school policy. ADA Professional Affairs Subcommittee. PMID- 1296901 TI - Establishing and sustaining state-of-the-art diabetes patient education programs: research and recommendations. AB - Frequently, diabetes educators in hospitals report meeting severe organizational barriers when attempting to implement advances in diabetes patient education (DPE). This paper reports on how eight successful diabetes patient education programs coped with potential barriers. The results are based on interviews of professionals who played central roles in introducing and sustaining the programs. Many of the identified problems centered around two issues--acquiring needed resources and communicating about the program to a variety of key groups. PMID- 1296903 TI - Nutritional considerations for other complications of diabetes. AB - The long-term complications of diabetes can have a devastating effect on an individual's self-esteem and outlook on life. Some preliminary studies have suggested that normalization of blood glucose levels may prevent or reverse the complications of diabetes in some individuals. Nutrition and diabetes meal planning play a critical role toward achieving this normalization. It is our job as diabetes educators to fully assess a patient's eating and life-style habits, as well as to recognize any complications from diabetes that the patient may be coping with at this time. Depending on the type of complication, diet alterations may need to be made to meet the patient's current needs, ie, reducing fiber content of the diet temporarily in patients with mild gastroparesis, or increasing the protein content of the diet in patients with nephropathy and a foot ulcer. By setting positive, attainable goals, the individual with diabetes may lead a healthier, more productive life in which the complications from diabetes can be prevented, reduced, or better tolerated. PMID- 1296904 TI - Nutritional concerns in gastrointestinal neuropathy. PMID- 1296905 TI - Nutritional concerns in diabetic nephropathy. PMID- 1296906 TI - Nutritional recommendations for cardiovascular complications of diabetes. PMID- 1296907 TI - [The occupational morbidity of workers in the foundry shops of Russia]. AB - Epidemiologic studies concerning the occupational morbidity of the foundry workers were carried out for the first time within the Russian Federation. Studies revealed the causes of diseases during 13 years, helped to create the structure and prevalence of entities and analysed the parameters of development and course of diseases, which helped to define the risk groups in silicosis and vibration disease formation and establish the prophylactic measures. PMID- 1296908 TI - [The characteristics of the development and course of pneumoconiosis under the conditions of a mountain climate]. AB - Analysis of pneumoconiosis course in workers exposed to dust in the mines of different altitudes showed, that the increased altitude augmented mountainous hypobaric hypoxia hasten the development of pneumoconiotic process and increase the number of nodular pneumoconiosis growing progressively worse. Pneumoconiosis develops considerably earlier and nodular forms predominate in the newcomers than in native workers. The frequency of such complications, as chronic bronchitis, asthmatic syndrome decreases in accordance with increasing of altitude which can be explained by the features of inhabitants' immunologic status and peculiarity of the mountainous climate. PMID- 1296909 TI - [Immunological studies in byssinosis from exposure to a mixed plant dust (jute, flax and kenaf]. AB - Complex immunologic studies using 1 and 2 level tests in 221 individuals (171 workers of raw material processing shops and 50 volunteers) revealed the similar changes in immunologic status of people suffering from byssinosis and workers of long length of service: decreased T-lymphocyte level (owing to T-helpers), phagocyte count and increased serum IgA, IgM in comparison with healthy people. Depressed phagocytosis in 79.6% of people facing byssinosis and 71% of workers with the long length of service can be caused by Gram negative bacteria, contaminating the air of industrial premises. Workers with the short length of service showed increased T-cells level (owing to T-suppressors) and lowered serum IgA, which can be considered as a primary immune response to the dust. PMID- 1296910 TI - [The results and outlook of a clinico-epidemiological study of the problem of the carcinogenic hazard in industry]. AB - Much attention is paid to clinical and epidemiological aspects of carcinogenic hazards in the production of asbestos textile, asbestos cement, friction, graphite and furniture goods. "Dose-response" relationship in exposure to occupational carcinogens was studied, criteria of occupational malignant neoplasma appurtenance were worked out, role of carcinogenic factors in malignant tumors of rare localisations was shown, signs of carcinogenic aerosols effects described and prophylactic measures suggested. PMID- 1296911 TI - [The immunostimulating properties of erythrocytes subjected to the action of ultraviolet irradiation and electromagnetic radiation during vibration exposure]. AB - Erythrocytes exposed to the ultraviolet (EUV) and electromagnetic (EEM) irradiation in healthy rats and rats exposed to vibration can stimulate humoral immune response to the ram erythrocytes. EEM had immune-stimulating activity higher. Heavy subpopulation of EEM and EUV had immune-stimulating activity, light subpopulation of EUV and EEM weakened the immune-stimulating effect caused by heavy EEM and EUV during vibration. PMID- 1296912 TI - [Local barotherapy in the combined treatment of occupational eczema]. AB - Drug-free techniques in the treatment of occupational dermatoses present a major clinical research problem area. The active hyperemia local barotherapy technique was tested as a possible solution to this problem. 52 occupational eczema cases were studied, part of which, in addition to routine drug therapy, were exposed to local barotherapy. The technique was found highly effective with markedly decreased temporary disability of the patients, improved immediate and long-term therapeutic effects, and limited administration of drugs. The technique can be recommended for wide use in clinical practice. PMID- 1296913 TI - [The gas chromatographic determination of dichlorobutenes and trichlorobutenes in washings from the skin]. AB - A sensitive selective method of unsaturated chlorated hydrocarbons detection by means of gas chromatography in skin was worked out. The limits are: for 3,4 dichlorobutene (DCB)-1-0.0024 mu g, for 1,3 DCB-2-0.0027 mu g, for 1,4-DCB-2 (cys)-0.0024 mu g, for 1,4-DCB-2 (trans)-0.0032 mu g, for 2,3,4 trichlorobutene (TCB)-1-0.0093 mu g in analysed volume. The method can be used for the sanitary control of the skin contamination in subjects exposed to DCB and TCB. PMID- 1296914 TI - [The gas chromatographic determination of sulfur- and oxygen-containing organic compounds released into the air of cellulose sulfate works]. AB - The article presents data on the design of sensitive, selective, useful in group analysis method to detect dimethylsulphide, dimethyldisulphide, acetic, propionic, butyric and valeric acids, methyl alcohol and phenol by means of gas chromatography in the air of cellulose sulphate production working zone. The methods were tested in examining the work conditions in Bratsk found-lavage shops. PMID- 1296915 TI - [Biological doses of noise and vibration]. PMID- 1296916 TI - [Tissue respiration in exposure to capron combustion products and the possibilities for its correction with a methemoglobin solution]. PMID- 1296917 TI - [Scientific and technical progress and railroad hygiene]. AB - Article deals with the experience in using of real way hygiene for improvement of the work conditions for railway workers. Positive influence of hygiene on the scientific and technologic progress in the studied branch of industry was approved. New scientific and industrial structures in hygiene and health care of the railway workers may be created during the construction of the new economic relationship. PMID- 1296919 TI - [Information on the activities of the International Commission on Occupational Health]. PMID- 1296918 TI - [Data on establishing the maximum permissible concentration of the herbicide levanil in the air of a work area]. PMID- 1296920 TI - [An assessment of the role of production factors in deep coal mines in the development of ischemic heart disease in miners]. PMID- 1296921 TI - [Diseases of the upper respiratory tract in workers in "dusty" jobs]. AB - Diseases of the upper respiratory tract are wide spread in the workers exposed to dust and closely correlate with the length of service. Pathologic process grows severe and disseminates the upper respiratory tract according to prolongation of the exposure to dust. The main pathologic mechanisms of process in the upper respiratory tract mucosa are: disorder of mucociliary clearance, disturbance of the regional immunity and the acid-base balance of tissues. Criteria of occupational connection of the nose, throat and larynx dystrophic diseases in workers exposed to dust are given. PMID- 1296922 TI - Construction of shuttle vectors for cloning in Escherichia coli and Acetobacter pasteurianus. AB - New cloning vectors were prepared with the aid of a large plasmid isolated from Acetobacter pasteurianus and from plasmids pBR322 and pUC4-KAPA. Of the prepared cloning vectors, pACK5 contains a gene coding for kanamycin resistance, pACT7 and pACT71 contain a gene coding for tetracycline resistance and vector pACG3 with a gene coding for both kanamycin and tetracycline resistance. The vectors prepared only contained the beginning of replication from the pAC1 plasmid and possessed the ability to replicate within E. coli and A. pasteurianus. The vectors are highly stable in both strains and during the 5-d cultivation under nonselective conditions are not eliminated. PMID- 1296923 TI - Interaction of 2-deoxy-D-glucose and adenine with phosphate anion uptake in yeast. AB - The transport of inorganic phosphate anions into yeast cells (after preincubation with glucose, fructose or another metabolizable sugar, and in the presence of glucose) shows two kinetic components with half-saturation constants of 40 mumol/L and 2.4 mmol/L. The uptake was strikingly stimulated by 2-deoxy-D-glucose (2-dGlc) at lower concentrations but inhibited above 100 mmol/L. A similar stimulation was caused by adenine (0.01-1 mmol/L) and a very small one by uracil and inorganic sulfate. It is suggested that either a phosphorylation reaction accompanies the transport (2-dGlc) or that some compounds stimulate the H(+) ATPase more than inorganic phosphate itself and thus increase its rate of transport. PMID- 1296925 TI - Effect of increasing methanol concentrations on physiology and cytology of Candida boidinii. AB - Concentration of methanol in the medium strongly affected not only the physiology but also the cytology of Candida boidinii strain 2 cells in a methanol-limited chemostat at a constant dilution rate D 0.1/h and at low pH 3.0. The formation of large cubic peroxisomes with high alcohol oxidase (AO) activity observed at low methanol concentration (S0 3 g/L) disappeared on increasing the methanol concentration in the inflow medium. The AO activity in the cells sharply decreased, followed by accumulation of riboflavin phosphate and residual methanol in the medium. The activity of catalase was relatively stable. At methanol concentration S0 > KI (KI equal to 12 g methanol per L), which included a substantial increase in methanol dissimilation, documented by higher formaldehyde and formate dehydrogenase activities and by lower yield coefficient on methanol, the yeast cells contained large lobe-shaped peroxisomes and a smaller number of larger mitochondria. The cells formed pseudomycelium with a thick septum between the mother and daughter cells. PMID- 1296926 TI - Citric acid production by Aspergillus niger using media containing low concentrations of glucose or corn starch. AB - By using an appropriate ratio of carbon source to mineral components, we obtained comparable citrate yields in media containing different concentrations of glucose. The enzyme system of inoculum passed on gradually from "growth" state to "production" state during the mould growth. In the starch medium, the critical factors of citric acid production are the aeration efficiency of the medium and the amylase formation of the strain. The air interruption exhibited a prolonged inhibition of the production rate but not of the citrate yield in glucose medium while those parameters in starch medium containing excessive urea were briefly but severely inhibited. After being affected by these unfavorable conditions, the production activity of Aspergillus niger could be restored by applying an appropriate fermentation process. PMID- 1296924 TI - Protective efficacy of different cell-wall fractions of Mycobacterium tuberculosis. AB - Immunization with various cell-wall fractions of M. tuberculosis H37Ra, progressively depleted of lipids (cell-wall-insoluble fraction; CWIF), soluble proteins (cell-wall core; CWC), mycolic acids and arabinogalactans (cell-wall protein-peptidoglycan complex; CW-PPC) elicited significant levels of both humoral and cell-mediated immune response. Mice immunized with these fractions, when challenged with an LD50 dose of M. tuberculosis H37Rv, exhibited significant protection as revealed by high survival rates and decreased bacterial load in lungs, liver and spleen, as compared to nonimmunized animals. PMID- 1296927 TI - Effect of nitrogen limitation and sporulation on sterol and lipid formation in Saccharomyces cerevisiae. AB - The content of sterols and lipids was compared in the cells of Saccharomyces cerevisiae cultivated in sporulation and the sterol-induction nitrogen-limited media. After 24 h the measured values in the two cultivations did not significantly differ. However, after subsequent 24 h, further formation of lipid globules and a corresponding increase of lipid and sterol content was detected only in the sterol-induction medium. To demonstrate the similarity of physiological state during the first day of the two cultivations, the combined cultivations were performed. Maximum sporulation, suggesting maximum similarity, of the two processes was achieved when the cells were grown in the sterol induction medium for 15 h and then transferred to a sporulation medium. PMID- 1296929 TI - Effect of crude bacterial lipids on the course of Listeria infection in mice. AB - Crude lipids from 37 strains belonging to 32 bacterial species were isolated. By injecting mice with lipids 5 d prior to challenge with a virulent strain of Listeria monocytogenes, immunostimulatory activity in 19 preparations was found. In general, lipids of Gram-negative bacteria appeared to be more effective. As to bacilli, an extraordinary activity was found in the lipids of Bacillus firmus. Lipids of various species of the genus Listeria were found to be active in approximately one-half of cases. Among other Gram-positive bacteria, significant activity of lipids was found in Corynebacterium xerosis, Propionibacterium acnes and BCG. The composition of fatty acids in the lipids did not differ significantly from that reported in the literature and their mutual differences could not explain the different biological activity. In selected strains of Gram negative bacteria lipids were repeatedly purified with anhydrous chloroform; these preparations were found to be inactive as compared with original chloroform methanol lipids. PMID- 1296928 TI - Bacterial endotoxins as potential antitumor agents. Tumor mass loss in mice treated with bacterial lipopolysaccharides of Shigella dysenteriae serovar 1. AB - Natural and modified preparations of lipopolysaccharides and lipopolysaccharide protein complexes isolated from the S- and R-form of Shigella dysenteriae serovar 1 were found to markedly inhibit the initial growth of mouse solid tumors derived from Nemeth-Kellner lymphoma, Gardner 6C3HED lymphoma, an ill-defined syngeneic lymphoma of DBA mice (Skalsky lymphoma) and LP-2 plasmacytoma. The biopreparations were given intraperitoneally, most frequently at a dose range from 50 to 200 micrograms per mouse; significant inhibitory effects on tumor growth were evidenced even in mice bearing tumors weighing 113 to 507 mg. PMID- 1296930 TI - Protein kinase C isozyme expression in human leukemia-lymphoma cell lines--an immunocytochemical study. AB - There have been an increasing number of reports describing a pivotal role for phosphorylation in cellular responses for cell differentiation and proliferation. We examined an immunocytochemical expression of protein kinase C(PKC) isozymes (type I, II, and III) in 22 leukemia-lymphoma cell lines. Of these cell lines, 21 expressed type II PKC and 17 showed the co-expression of both types II and III PKC in varying degree. The cell line without PKC activity showed far less [3H] TdR uptake and no heterotransplantation in nude mice. Types II and III PKC appear to relate to cell proliferation in certain leukemia-lymphoma cell lines. PMID- 1296931 TI - Mitoxantrone and intermediate-dose cytosine arabinoside for poor-risk acute leukemias: response to treatment and factors influencing outcome. AB - Mitoxantrone (MIT, 12 mg/m2, i.v. 5 days) and intermediate-dose cytosine arabinoside (IDAC 1 g/m2/12 h, i.v. 3 days) was given to 43 patients with poor risk acute leukemias (AL). Moderate or severe toxicity was infrequent. The proportion of complete remissions (CR) in the main patient categories was as follows: 15/18 (85 per cent) in acute myeloid leukemia (AML) in the first relapse, 2/6 in ALL in the first relapse, 0/2 in AML in relapse after bone marrow transplantation (BMT), 2/7 in AML refractory to first-line treatment (REF-AL), and 1/6 in postmyelodysplastic (PMD-AL) plus secondary AL (S-AL). The mortality rate during induction was 23 per cent. Median duration of CR was 24 weeks. The multivariate prognostic factor analysis on CR obtention showed that data concerning treatment for the first relapse and platelet count higher than the median of the series were favourable. On the contrary, PMD-AL, S-AL and REF-AL were unfavourable situations. A percentage of marrow erythroblasts superior to the median was a favourable prognostic factor for survival. Finally, the duration of CR after MIT-IDAC was directly related to the duration of previous CR. In conclusion, MIT-IDAC was highly effective to attain CR in AML in the first relapse. However, due to the poor long-term results in these patients, additional measures are recommended after CR. PMID- 1296932 TI - Production of multiple cytokines by Hodgkin's disease derived cell lines. AB - The production of cytokines was analysed in Hodgkin's disease (HD) derived cell lines by enzyme linked immunosorbent tests (ELISA) and Northern blot experiments. Our results demonstrate that HD derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, TNF alpha, TNF beta and GM-CSF but not IL1 beta, IL2, IL3 and G-CSF. In cell lines with a high expression of CD25 (the light chain of the IL2 receptor), we found soluble IL2 receptors in the supernatants. In addition, receptors for IL6 could be detected in most of the HD derived cell lines. However the growth of HD derived cell lines, which produce IL6 and IL6 receptors could not be inhibited by anti-IL6 antibodies. From our data we conclude, that IL6 and additional cytokines may be involved in the biology of HD. PMID- 1296933 TI - Cytophagic histiocytic panniculitis: a diagnostic dilemma. AB - Cytophagic histiocytic panniculitis (CHP) is a recently recognized entity that frequently poses a perplexing diagnostic problem. Although the classical case presents with a relapsing fever, subcutaneous nodules, pancytopenia and liver dysfunction, most patients have in addition a multitude of other manifestations which confuse the clinical picture. Notwithstanding the variable clinical course, the disease frequently terminates in fatal hemorrhage. Diagnosis is based on histological features. A lobular panniculitis with an infiltrate of cytologically benign cytophagocytic histiocytes in skin nodules is the sine qua non of CHP. Hence, a deep skin biopsy which includes subcutaneous fat is mandatory to establish the diagnosis. Published information regarding this newly described entity remains scarce and we report two cases of CHP, one occurring in a 30-year old Kadazan man and another in a 17-year-old Chinese woman seen at the University Hospital, Kuala Lumpur. The latter case presented with exudative ascites, an unusual feature, possibly due to intra-abdominal panniculitis. In addition, we record the development of cirrhosis in the same patient. PMID- 1296934 TI - Prognostic significance of karyotype analysis in children with acute lymphoblastic leukemia. AB - Chromosome studies, using bone marrow samples of 26 pretreated children (below 15 years of age) with Acute Lymphoblastic Leukemia were carried out to explore the potentialities of applying chromosomal findings as a prognostic indicator in these patients. Abnormal karyotype was identified in 15 patients (57.6 per cent). The chromosomes frequently involved in non-random numerical abnormalities were Nos. 8, 18 and 21. Structural chromosome changes observed consisted of deletion 6q- and translocation t (4;11). After karyotype analysis, patients were grouped into subsets on the basis of the karyotype pattern observed. They were followed up to evaluate their prognosis and survival period. Patients showing hyperdiploid clone with greater than 51 chromosomes had the best prognosis. Patients with normal karyotype and patients with deletion of the long arm of chromosome 6 showed intermediate prognosis whereas patients showing t (4;11), trisomy 8, trisomy 18, trisomy 21, and hypodiploid karyotype were associated with worst prognosis. Thus, karyotype analysis before treatment helps to classify ALL patients as poor, intermediate and good prognosis groups and on this basis therapy can be designed accordingly. PMID- 1296936 TI - Effect of berberine on enterotoxin-induced intestinal fluid accumulation in rats. AB - We have determined the effects of berberine (Berberis aristita) on intestinal fluid accumulation due to enterotoxigenic E. coli (ETEC) heat-stable (ST) toxin in suckling (24-days old) Wistar rats. Intestinal fluid accumulation occurred in suckling Wistar rats by administration of culture filtrate containing ST producing ETEC in serial dilutions up to 1/8 dilution by oral or intragastric route. When berberine (0.1 mg) and 1/8 dilution of ST-toxin were given together by oral or intragastric injection, a significant (p < 0.01) reduction in fluid accumulation was observed. Neither treatment with berberine orally before intragastric injection of ST-toxin nor intragastric administration of berberine after ST-toxin reduced the fluid accumulation due to ST-toxin. PMID- 1296935 TI - Trends in the management of childhood diarrhoea in Egypt: 1979-1990. AB - Until 1979, diarrhoeal disease accounted for roughly half of all infant and childhood deaths in Egypt, partly because curative care was largely inappropriate. The National Control of Diarrhoeal Diseases Project (NCDDP) addressed this problem from 1982 to 1991. Since 1979 many aspects of diarrhoeal disease in Egypt have been addressed in many studies. This paper reviews that literature, finding considerable improvements in case management, particularly in the use of oral rehydration solution and in feeding during diarrhoeal episodes. This is due primarily to the NCDDP. At the same time diarrhoeal mortality declined rapidly, both absolutely and as a percentage of total mortality. Persistent diarrhoeas, which have become an increasing proportion of the remaining mortality, have not been satisfactorily addressed, and irrational treatment with drugs remains a major problem. PMID- 1296937 TI - Evaluation of preventive health services for hospitalised children under a child health programme. AB - In the hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, the Child Health Programme (CHP) has been offering preventive health care services to about 60,000 patients per year. The patient populations are mostly children who stay with their mothers or other relatives. In this programme, health education, immunisation and nutrition rehabilitation services are offered. Health education is offered as group discussion and face-to-face interaction between the educator and the mother. Immunisation is offered daily from 0700h to 1900h to all children and women attending the hospital. Nutrition rehabilitation services, both inpatient and outpatient, are offered to severely undernourished children. These preventive services are implemented by health workers and health assistants. All attendants and adult patients participate in health education sessions. More than 80% of unimmunized children and 50% of unimmunized women receive immunisation. The experience of the CHP shows that it is possible to offer different preventive health care services to all attendants and patients attending a busy hospital. PMID- 1296938 TI - Production of chitinase by enterotoxigenic Aeromonas species isolated from clinical and environmental sources. AB - Thirty-six isolates of Aeromonas, 13 from children and 23 from the environment were tested for production of chitinase in culture supernatants. Thirty-four isolates of the three species (91% clinical and 96% environmental) produced constitutive chitinase. The environmental isolates elaborated significantly more (p < 0.005) of the enzyme than those from the children. Four of the environmental isolates also produced inducible chitinase. All isolates of Aeromonas were enterotoxic, however, the isolates producing inducible chitinase showed significantly higher enterotoxic activity. This study indicates that there is correlation between production of enterotoxin and chitinase in Aeromonas species. PMID- 1296939 TI - Diarrhoea and feeding practices of young children attending two selected urban clinics in Dhaka. AB - Data were collected from 150 mothers attending the outpatient departments (OPD) of one maternal-child health (MCH) clinic and one paediatric hospital in Dhaka for treatment of diarrhoea of their children during the period from March '90 to May '90. Feeding practices before and after occurrence of diarrhoea were evaluated to determine the knowledge and practice of changes in dietary patterns. The majority (58.67%) of children, who were all less than 5 years old, were in the younger age group (0-1 year) with slightly more occurrence in male children. The incidence rate was higher among children of low-income families and uneducated mothers. Among the children, 60.67% had 6-8 loose stools per day and 66% suffered from watery diarrhoea, which was mostly in the younger (0-1 year) age group (p < 0.001). The majority (60%) of mothers had incorrect knowledge about changing their children's diets; only 40% knew how to do it correctly, which was significantly (p < 0.001) related to the educational level. During diarrhoeal episodes among the 0-1 year age group, the number of mothers exclusively breastfeeding increased considerably (14.77% to 35.23%), and the number of mothers only partially breastfeeding decreased (62.5% to 43.18%), withholding (48.38%) or adding (9.68%) some items, or both (13.98%), showing significant change (p < 0.005) in diet with the education of mothers. "Some food items cause diarrhoea, others increase the frequency of loose motion, and withholding or adding some food cures it," they believed. The results of the study show that, through proper nutrition education, mothers can be helped to provide better home management of diarrhoea. PMID- 1296940 TI - Maternal practices and risk factors for dehydration from diarrhoea in young children: a case-control study in central Thailand slums. AB - To determine factors related to dehydration from diarrhoea, we conducted a hospital-based, case-control study in children aged 24 months or younger who had acute watery diarrhoea and attended Chonburi Regional Hospital in central Thailand during November 1988 through May 1989. The study compared 48 cases who had moderate or severe dehydration with 48 controls who had no dehydration. Both cases and controls belonged to low socioeconomic families and were living in urban slum areas. They had adequate health care facilities and access to ORS packets. Overall, 56% of the mothers used ORS solution at home. None of the mothers knew how to administer ORS, i.e. the fluid was not given at the onset of diarrhoea to prevent dehydration, and they gave no more than 60 ml over a 24-hour period to their dehydrated children. They also did not use home fluids. Multivariate analysis of data showed two factors significantly associated with dehydration: children's dirty fingernails that indicated inadequate maternal hygiene-related behaviour (Odds Ratio 6.4; 95% Confidence Intervals 1.5-27.6, p < 0.01), and frequency of vomiting in the 24 hours before rehydration (Odds Ratio 1.3; 95% Confidence Intervals 1.1-1.6, p < 0.001). Cases and controls had similar aetiologic agents and nutritional status. Providing proper education to mothers about oral rehydration therapy with special emphasis on the volume of ORS to be given, along with guidance to improve their personal hygiene should be considered important interventions in reducing the risk of dehydration and deaths from diarrhoea in these children. PMID- 1296941 TI - Isolation of enterotoxigenic Vibrio cholerae non-01 from the Buriganga river and two ponds of Dhaka, Bangladesh. AB - Vibrio cholerae 01 is usually considered the most toxigenic member of the Vibrionaceae and V. cholerae non-01 isolated from the environment is non toxigenic. In our survey of the pollution of some aquatic environments in and around Dhaka, Bangladesh, we wanted to investigate the toxigenicity of V. cholerae non-01 isolated from water and sediment samples of the Buriganga river and two ponds in Dhaka, in the rabbit ileal loop (RIL) model. Fluid accumulation was induced by 18 of 28 live cultures and five of 18 cell-free culture filtrates in RIL. Seven of ten V. cholerae non-01 which failed to induce fluid in RIL were subjected to repeated passage in rabbit gut. Within two consecutive passages, all the strains could induce fluid in rabbit gut. Both toxigenic and non-toxigenic strains were uniformly sensitive to chloramphenicol and gentamicin but resistant to neomycin, novobiocin, polymyxin-B, streptomycin and vancomycin. Tetracycline sensitivity was found among eight of 17 toxigenic and six of 12 non-toxigenic strains. Sensitivity to trimethoprime-sulfa-methoxazole was noted among seven of 17 toxigenic and six of 12 non-toxigenic strains. Occurrence of enterotoxigenic and drug-resistant V. cholerae non-01 in the surface water is a public health hazard. PMID- 1296942 TI - Biochemical characteristics and enterotoxicity of Aeromonas species isolated from man and environment. AB - A total of 147 isolates of Aeromonas spp., of which 54 were isolated from children and adults with diarrhoea, 44 from variety of water sources and 49 from environmental sources, were tested for enterotoxin production and its correlation with biochemical characters. Lysine was decarboxylated by 38% of A. hydrophila, 35% of A. sobria and 20% of A. caviae. Majority strains were unable to utilise citrate as the sole source of carbon except one of A. hydrophila, 8 of A. sobria and 6 of A. caviae. Beta-haemolysis was shown by 108 isolates that included 79% of A. hydrophila, 76% of A. sobria and 70% A. caviae. About 56% of Aeromonas strains including A. caviae caused fluid accumulation in the rabbit ileal loop in the initial tests and the remaining did so after 1-3 consecutive passages. Enterotoxin production did not correlate with the positive biochemical characters such as Voges-Prauskauer reaction, lysin decarboxylation, haemolysin production, citrate utilisation and failure to ferment arabinose either singly or in combination. This study indicates that enterotoxicity of Aeromonas may not be correlated with any of the biochemical characters either singly or in combination. PMID- 1296943 TI - Clinical and autopsy findings of a nine-month-old girl with malnutrition and pneumonia. Postmortem study case-15/91. PMID- 1296944 TI - Bibliography on diarrhoeal diseases. PMID- 1296945 TI - Studies on the infectivity of gametocytes of Plasmodium berghei (NK 65) in Anopheles stephensi. AB - The infectivity of gametocytes of Plasmodium berghei (NK 65) has been studied in laboratory bred Anopheles stephensi. Mosquitoes were fed daily on infected male and female Mastomys natalensis and subsequent development of the oocysts was monitored in the midguts. Maximum number of oocysts were found in mosquitoes which were fed on infected female mastomys on D8 and in male mastomys on D7 post inoculation. During the next peak of gametocytaemia, very few oocysts developed. These findings suggest that gametocytes are maximally infective only during the first peak, later on their infectivity declines although having sufficient number of gametocytes in the circulation. PMID- 1296946 TI - Multi-drug resistance in salmonellae isolated from enteric fever cases at Porur- a semi urban area near Madras City. AB - A total of 249 isolations of Salmonella were made during 1991, of which 67.46 per cent were resistant to chloramphenicol. Resistance to ampicillin, co-trimoxazole and amoxycillin was higher (82.91, 77.69, 81.42 per cent respectively). Salmonella typhi was predominant agent forming 94.78 per cent and Salmonella paratyphi A caused the remaining infections. 44.98 per cent of the isolations were in children. This outbreak has been discussed in the light of other reports from India. PMID- 1296947 TI - Efficacy of diethylcarbamazine medicated salt in interrupting Brugia malayi transmission in hill tribe settlements in Kerala State. AB - A filariasis survey carried out about eight years after achieving zero microfilaria (mf) rates following administration of diethylcarbamazine (DEC) medicated salt in the Kani hill tribe settlements in Quilon and Thiruvananthapuram districts of Kerala State revealed that there was no reappearance of Brugia malayi infection in the experimental areas. Mf rates were maintained at zero level in the experimental villages, while in the control villages, 2.9 per cent mf positives were observed. Mansonia (Mansonioides) uniformis dissected did not reveal filarial infection. It is concluded that DEC medicated salt regime in the experimental areas of Kani hill tribe settlements has been successful in effectively interrupting B. malayi transmission. Pilot studies in other B. malayi endemic areas of India using DEC medicated salt regime with the objective of eliminating B. malayi transmission are advocated, since the parasite has a restricted distribution in India and is already showing a declining trend. PMID- 1296948 TI - Indoor resting density, survival rate and host preference of Culex quinquefasciatus say (Diptera: Culicidae) in Mysore City. AB - Monthly indoor resting density, age distribution, survival rate and host preference of Culex quinquefasciatus, a filariasis vector were studied from June 1988 to May 1989 in Mysore city. During this period, a total of 7522 adults were collected in 72 man-hour of search spreading to twelve spots covering the entire city. The annual per man-hour density observed was 104.5, being 76.8 for female and 24.3 for male. Nulliparous and parous (1-parous and 2-parous) mosquitoes were collected throughout the year while 3-parous and 4-parous mosquitoes were recorded during cold and rainy seasons only showing an increase in the number of gonotrophic cycles. Precipitin test of blood smears from the gut content of C. quinquefasciatus was done by taking 2536 mosquito blood smears. Of these, 94.1 per cent preferred human blood, 1.4 per cent bovine and 3 per cent avain. As the species evaluated is a major vector of filariasis, the present study on its resting density and the host preference will be helpful in vector monitoring in Mysore city. Various results on this species at Mysore have been discussed in the light of earlier studies conducted elsewhere. PMID- 1296949 TI - Inhibition of Salmonella ferlac by enterobacteria under in-vitro conditions. AB - Interactions of Proteus morganii, Proteus mirabilis, Proteus sp. Klebsiella oxaenae and Serratia marcescens isolated from vegetable salads of mass feeding systems with Salmonella ferlac (a new subgenus VI of Salmonella) isolated from a hostel cook's hands and lizard droppings were recorded following in-vitro nephelometric analysis. Nephelometric analysis revealed inhibition of S. ferlac by all the tested isolates from fifth hour of mixed culture interaction. K. oxaenae was the strong inhibitor. PMID- 1296950 TI - An indirect fluorescent antibody (IFA) test for the serodiagnosis of Kala-Azar. AB - The IFA test developed using Leishmania donovani promastigote and amastigote antigens showed very high antibody titre in clinically and parasitologically established cases (30) of kala-azar, the geometrical mean reciprocal titre (GMRT) being 870 +/- 5.4 and 5370 +/- 1.80 respectively with the two antigens. In contrast, the GMRT of normal subjects of endemic area was only 12.44 +/- 6.19 and 80.35 +/- 1.66 respectively with these antigens. None of the subjects from non endemic area suffering with other parasitic diseases, such as malaria, filaria, amoebiasis, leprosy or tuberculosis (20 cases each) gave a positive response to any of the antigen. The test holds promise in the diagnosis of Kala-azar. PMID- 1296951 TI - Changes in the level of biogenic amines in experimentally infected and DEC treated proxy host mice. AB - The levels of biogenic amines, viz., epinephrine, histamine and dopamine were significantly altered in the blood and brain of the proxy host mice which were infected with the mf of Setaria digitata, a filarial parasite. When DEC, the drug of choice was administered to the infected mice, serotonine level was enhanced while the histamine level was decreased. The results were similar in normal mice which were given DEC. PMID- 1296952 TI - Partial purification of acid phosphomonoesterase in axenically grown Entamoeba histolytica NIH-200. AB - Entamoeba histolytica possesses significant acid phosphatase activity as compared to alkaline phosphatase activity. The acid phosphatase activity in the amoebic cells eluted at higher saline concentration as three distinct peaks at 200, 300 and 400 mM sodium chloride. PMID- 1296953 TI - Nasal carriage of Staphylococcus aureus in hospital staff and its antibiotic sensitivity in Enugu, Nigeria. AB - The nasal carriage of Staphylococcus aureus was investigated in 475 hospital staff of different categories. The overall carriage was 34.42 per cent with a significantly higher rate in females (67.53 per cent) than in males (23.81 per cent). Nurses, orderlies and attending physicians had a higher carriage rate than other categories of staff investigated. The rate was higher in personnel working in accident, neonatal and postnatal wards than in other wards. As many as 51.94 per cent of the strains of S. aureus were resistant to penicillin while 22.72 per cent of them were resistant to ampicillin. PMID- 1296955 TI - Chemoprophylaxis studies in cholera: a review of selective works. PMID- 1296954 TI - Colonic immunity in patients and amoebic liver abscess. AB - Secretory immunoglobulin A (S-IgA), coproantibody titre (antiamoebic) and IgA, IgG, IgM immunocytes in rectal mucosa were studied in 13 patients with amoebic liver abscess (ALA) prior to and 4-6 weeks after completion of antiamoebic therapy. Ten asymptomatic Entamoeba histolytica cyst passers and 17 healthy age and sex matched volunteers served as controls. Fecal S-IgA levels and counts of IgA bearing immunocytes in mucosa were significantly higher in patients with ALA and cyst passers as compared to healthy controls and showed a significant fall after treatment. Fecal antiamoebic antibodies were high in cyst passers and in cases of ALA after treatment. Raised levels of S-IgA and IgA class immunocyte counts probably indicate a local mucosal immune response directed at containing the infection. PMID- 1296956 TI - Status of intestinal parasitic infections in Loni--a rural area of Ahmednagar District of Maharashtra. PMID- 1296957 TI - Characterization of Bacillus spp. isolated from mosquito larvae in a Filariasis endemic area. PMID- 1296958 TI - Study of breeding habitats of sandflies--preliminary approach. PMID- 1296959 TI - Occurrence of entomophilic nematode infestation among phlebotomid sandfly, Phlebotomus papatasi--a preliminary report. AB - Infestation of a nematode parasite was observed in the natural population of Phlebotomus papatasi in Pondicherry, India. Of the 877 males and 959 females sandflies examined for the natural infection, 11 females were found infested with nematodes (0.59%). The number of juveniles and/or eggs of nematodes per infected fly ranged from 1 to 192 (mean 51.36 +/- S.D 55.95). The presence of a stylet at the opening of the dorsal oesophageal duct suggests that the parasite belongs to the super family Tylenchoidea. PMID- 1296960 TI - Hepatitis C virus infection in blood donors in Egypt. AB - A study was carried out on 90 serum samples from non-professional blood donors to find out the relative prevalence of HBV and HCV among those blood donors. Results demonstrated overall positivity rate of 14.4% for anti-HCV by RIBA test. The percentage of reactive sera was 6% for the age group of 20 to below 30 years, and 37.5% in those aged above 30 years, and this difference was statistically significant. Considering the combined reactivity of the tested 90 sera for anti HBs and anti-HCV, the results showed that 41.1% of the sera were positive for anti-HBs; 10% reacted positively with both anti-HBs and anti-HCV, and 4.4% of the sera were positive for anti-HCV only. The high prevalence of anti-HCV in this study (14.4%) exceeds that reported in other countries, and is comparable with that of Saeed and associates (1991). These results may indicate endemicity of HCV in Egypt and/or a possible role of the endemic schistosomiasis. On the basis of data, suggesting that anti-HCV reflects persistent infection rather than immunity, screening for anti-HCV should be included in all blood transfusion services to exclude HCV which is responsible for 90% of PTH (Van der Poel et al., 1990; Weiner et al., 1990; and Esteban et al., 1991). The remarkably high seroprevalence of anti-HCV among Egyptian volunteer blood donors, which has not so far been reported from other countries, should be thoroughly studied. This should cover many aspects including large epidemiological studies, factors pertinent to Egypt as schistosomiasis, and other possible factors that might enhance HCV transmission in Egyptian population. High risk groups as the polytransfused and renal dialysis patients should be studied. Needless to say that, an accurate measure of HCV prevalence depends on specificity and sensitivity of the employed laboratory diagnostic tests; development of new tests for the detection of antibodies to HCV, together with development of tests for other markers such as HCV antigen and the polymerase chain reaction to detect HCV DNA in blood, will be of great help. PMID- 1296962 TI - Breastfeeding and fertility. Part II: Breastfeeding practices. AB - A cross-sectional survey described the current breastfeeding status and antenatal care of 1134 urban mothers, attending MCH centers in Alexandria governorate and gave birth within the last two years, was carried out. The results indicated that the median duration of breastfeeding was 14 months. At six month postpartum the proportion of breastfeeding mothers was 0.8. The mean age of weaning was 20.7 (+/ 4.1) months. Less than 80% of mothers attended the antenatal visits. Information about breastfeeding was provided to 80% of mothers who attended the antenatal visits. PMID- 1296961 TI - Beta-glucuronidase and hyperbilirubinemia in breast-fed versus formula-fed babies. AB - Breast milk and formula milk and the corresponding serum samples from 20 breast fed babies, 20 formula-fed babies, and their mothers were examined at 3 days of age for beta-glucuronidase enzyme. Serum indirect bilirubin levels were also examined for all the infants. Serum indirect bilirubin concentrations were significantly higher (p < 0.001) in breast-fed (4.87 +/- 2.4 mg/dl) than in formula-fed infants (1.04 +/- 0.5 mg/dl). beta-glucuronidase activity in formula milk was negligible, while that in human milk was considerable (468.26 +/- 220.8 Sigma units/ml) and was correlated (p < 0.05) with that in the serum of the breast-fed (66.13 +/- 18.1 Sigma units/ml) than in formula fed infants (52.08 +/- 11.9 Sigma units/ml) and a significant (p < 0.05) correlation was found between its serum level and serum indirect bilirubin in both breast and formula fed infants. Also in breast-fed infants serum bilirubin concentrations were related to beta-glucuronidase activity in breast milk (p < 0.05): Breast milk beta glucuronidase--by facilitating intestinal reabsorption of bilirubin--seems to be an important factor in the neonatal hyperbilirubinemia of breast-fed babies. PMID- 1296963 TI - When and why Ain Shams University students started smoking? AB - The present study was carried out to determine the prevalence, age of first starting smoking and the risk factors associated with taking up regular smoking. The study included 1291 University students (861 males and 430 females), their ages ranged from 17 to 28 years. The over all percentage of smokers was 37.9% (52% males and 9% females), and 21% of males and 12% of females started smoking before the age of 14 and 80% of males and 57% of females before reaching 18 years of age. Smoker peer colleagues, high income, owning of a car, and family troubles, using drugs, smoking hashish and drinking alcohol are significant associated risk factors to taking up smoking. PMID- 1296964 TI - Breast-feeding and fertility. Part I: Lactational amenorrhoea. AB - A cross-sectional survey describing the current fertility performance and breast feeding of 1134 urban mothers, who gave birth within the last 2 years was carried out. Mothers were recruited from MCH centers in Alexandria governorate. The results indicated that the mean time elapsed since birth before return of menstruation was (5.1 +/- 4.3) months for breast-feeding mothers and (2.5 +/- 2.3) months for non-breast feeding mothers. At four-month of postpartum period, 50% of the mothers were still amenorrhoeic and at six-month, 31% of the mothers were still amenorrhoeic. A total confirmed pregnancies was 8.5% and 3% of new pregnancies occurred during amenorrhoea and while women were breast-feeding. Use of contraceptives was practiced by 57% of mothers, with 65% of all users starting as early as the second month. PMID- 1296965 TI - Socio-cultural and nutritional risk factors of adolescents and young pregnant women in an endemic area of schistosomiasis. AB - The present study was undertaken in order to investigate the social, cultural, behavioral and environmental factors and their impact on the health and nutrition of young pregnant women and adolescent girls aged between 11 and 22 years, living in a rural area known to be endemic of schistosomiasis. A total sample of 34 pregnant women, 30 adolescent girls and 5 married never-pregnant women were recruited initially. The results revealed that early marriage before legal age still occur in rural areas in Egypt (15%). The mean age of marriage was 17.5 years (+/- 1.8) while the mean age at the first conception was 17.9 years (+/- 1.6). A high rate of illiteracy (72%) which was statistically significant was found among married women than adolescent girls. The daily intake of most nutrients were below the RDA except for protein and vitamin C among pregnant respondents. Iron, calcium and riboflavin were the nutrients most poorly supplied by the diets of pregnant women and adolescent girls. A significant statistical difference was found between the two groups in the intake of iron (z = 3.20, p < 0.05). About 60% of pregnant women and 80% of adolescent girls reported contact with canal water during household activities and field work. There was a lack of knowledge as regards schistosomiasis among respondents especially pregnant ones. Home deliveries with the assistance of traditional birth attendants is still the first choice by most of the pregnant respondents. PMID- 1296966 TI - A study of the epidemiology of preterm labor. AB - A case-control study was designed in order to identify risk factors associated with preterm labor. All cases fulfilling the criteria of eligibility as preterm labor and attending the Ain Shams University Maternity Hospital during the period from January 1991 to June 1991 were included in the study. In the meanwhile, all women delivering after the 37th week of gestation during that period and in the same hospital and matched according to age (+/- 5 years) were included as the control group. Two hundred and thirty four cases and 216 controls were included in the study. An interview was performed to fill an epidemiologic and clinical questionnaire. Results showed that the lower the socioeconomic standard, the more the risk for preterm labor (p < 0.05), smoking whether active or passive is associated with preterm labor (p < 0.001), threatened or induced abortion, unwanted pregnancy, psychological trauma and surgical intervention during current pregnancy are associated with preterm labor (p < 0.001). History of preterm labor is associated with the present condition (p < 0.001). Anemia, hypertension, body weight less than 70 kgm are associated with preterm labor (p < 0.001). PMID- 1296967 TI - Salmonella-induced enteritis. Clinical, serotypes and treatment. AB - Salmonella-induced enteritis is a widespread cause of morbidity and mortality especially in developing countries. The frequency of different Salmonella serotypes in different areas varies according to time and locality. The prevalence of different Salmonella serotypes in Yanbu area was studied in 136 stool cultures from patients admitted with gastroenteritis, to the medical ward of Royal Commission Hospital in the period 1/6/1991 to 30/10/1991. Fifteen different Salmonella serotypes were determined among 31 positive Salmonella isolates and all were of the gastroenteric group, diarrhoeagenic but noninvasive. The most common serotype was S. typhimurium (45.16%) followed by S. enteritidis (9.62%) then S. virchow (6.46%). Other forms of Salmonella were isolated from one patient each 3.23%, S. paratyphi B java, S. heidelberg, S. livingstone, S. infantis, S. bovis morbificans, S. corvallis, S. eastbourne, S. give, S. senftenberg, S. poona, S. adelaide, and S. johannesburg. Saudi patients comprised about 71% and 29% were patients of four different nationalities. Antibiograms of these cultures proved to be all sensitive to norfloxacin with different forms of resistance to chloramphenicol, ampicillin and trimethoprim. Norfloxacin proved to be effective in the treatment of resistant forms of Salmonella with negligible side effects and wide safety range. PMID- 1296968 TI - Antibody level after measles vaccination. AB - The present study was designed to estimate the level of measles IgG antibody in infants early after vaccination and in preschool children to determine their immune status. Three groups were studied: Group I, unvaccinated infants, Group II, recently vaccinated infants and Group III vaccinated preschool children. Measles IgG antibody was measured using the ELISA technique. The study showed that 90% (18/20) of the unvaccinated Group I infants were seronegative and only 10% were seropositive for measles IgG antibody representing most probably persisting maternal antibodies. Fifty percent (15/30) of recently vaccinated Group II infants were seropositive. A statistically significant higher antibody level was observed in Group II infants in comparison to those of Group I. The majority of seropositive infants of Group II (10/15 = 66.7%) showed high antibody level representing successful vaccination. Seropositives represented 77.4% (24/31) of Group III preschool children and the majority of them 75% (18/24) showed high antibody level which was significantly higher than the comparable in Group II infants, most probably due to subclinical infection in addition to successful vaccination. Fifty percent (15/30) of Group II infants and 22.6% (7/31) of Group III children were seronegative, more likely due to failure of initial vaccination. PMID- 1296969 TI - Familial and sociological correlates of behavioral deviance among juvenile boy delinquents in Alexandria. AB - Sixty five institutionalized juvenile boy delinquents aged 11 to 21 years were screened for behavioral deviance in relation to familial and social variables. Data of behavioral deviant children was compared with similar data available for the group of children not identified by the screen. Results of this study revealed statistical associations between behavioral deviance among juvenile boy delinquents and most of the studied familial/social backgrounds and morbid parent child relationships. Knowledge about these issues should be applied in understanding and planning the treatment of the delinquent. PMID- 1296970 TI - Influence of job characteristics on job satisfaction of pediatric nurses. AB - This study was conducted to determine the possible influence of job characteristics on job satisfaction of pediatric nurses. Eighty-nine pediatric nurses working in the pediatric units of the Maternity and Children Hospital in Jeddah, Saudi Arabia comprised the subject of the present study. A questionnaire of three parts was synthesized for this study. Part I is a multifaceted measure of job satisfaction (Smith et al., 1969) and known as job Descriptive Index. Part II is a job Characteristics Inventory (J.C.I) of 30 items developed by (Sims et al., 1976) to determine nurses perception of six characteristics, namely, variety, autonomy, task identity, feed back, dealing with others, and friendship opportunities. Part III comprised five demographic items. The study revealed that the overall degree of satisfaction of pediatric nurses was found to be relatively low with a mean percentage score of only 58.52%. Regarding the five job satisfaction subscales, nature of work (nursing of children) showed the highest mean percentage score. The study illustrates a positive strong correlation between job characteristics and job satisfaction with variety, task identity, and feedback being the statistically significant individual characteristics. PMID- 1296971 TI - Some health aspects in instituted primary school children. AB - This study was conducted on 193 children aged 6-12 years. They were 93 children (65 boys and 28 girls) living in two residential institutions in Cairo and 100 non-instituted children (65 boys and 35 girls) who are their matched school peers. Anthropometric measurements, complete physical examination and laboratory investigations including haemoglobin concentration, complete urine and stool analysis were performed to all children. Results showed that 25.81% of instituted children have body weights below the 10th percentile and 60.22% have heights below the 10th percentile compared to 14% and 37% of non-instituted children respectively. The differences were statistically significant. The prevalence of vitamin deficiency manifestations, and skin diseases was significantly higher in the instituted group. The mean haemoglobin concentration was lower in the instituted children, with a significant difference in all males and in females aged 9-12 years. Intestinal parasitic infections were more prevalent in the instituted children. It was found that among instituted children weight and height were most affected by cause of institution and number of children cared for by a substitute mother while hemoglobin concentration was most affected by age at institution and the level of education of the substitute mother. PMID- 1296972 TI - Genetic study of phenylketonuria. AB - Among four hundred and eighty mentally retarded patients referred to the Human Genetics clinic, Medical Research Institute, Alexandria University, Egypt; twelve cases were found to have pku, ten cases had classical pku and 2 cases atypical pku. Genetic studies of those patients and their families revealed segregation of autosomal gene(s) that are responsible for the development of the disorder with a recurrence risk of 0.283 +/- (1.96)(0.066). The high average inbreeding Coefficient indicated the important role played by consanguinity. Heterozygote detection is very important to normal sibs of affected patients to provide proper genetic counseling. Dietary management of the young infants in the first three months showed normal growth and development. Behavioral improvement was observed in cases who were treated late despite the fact that they were mentally retarded. Dietary control should be continued for a long life time to obtain good outcome in both sexes and to prevent the risk of fetal damage during child-bearing age in females. PMID- 1296973 TI - An epidemiologic study of ovarian cancer. Part 1: Reproductive and social factors. AB - This study was undertaken to investigate the risk factors of ovarian cancer. A retrospective analysis was used in this study where 52 ovarian cancer cases and an equal number of a control group were obtained from the Western region of Saudi Arabia. Analysis of data showed that cases and controls did not significantly differ in any of the studied social factors, marital status, social class, and family history of cancer ovary. However, when reproductive factors were considered, the mean values of parity and number of abortions, but not age at first birth. Were found to differ significantly between cases and controls. PMID- 1296974 TI - A study of some trace elements in fingernail and hair of Egyptian bilharzial patients using short neutron activation. AB - The concentration of 10 elements has been determined in fingernail and hair of four groups representing normal and hepatosplenic (bilharzial) subjects. Samples were collected from rural inhabitants to the east of Alexandria City and irradiated with thermal neutrons from a Triga Mark III Reactor, for 10 minutes. Measurements were made using HPGe detector, ADC and PDP 11/34. The analysis were performed using the RAYGUNprogram. The results showed an increase in the concentration of Al, Cl and I in both fingernail and hair of bilharzial patients than normal while Mg, Ca, K, Mn, Cu, and Sr decreased. Most of the elements showed a higher concentration in fingernail than in hair. PMID- 1296975 TI - Serodiagnosis of visceral leishmaniasis among primary school children in Alexandria. AB - The present study was carried out on a primary school children of El-Max area, west of Alexandria to assess their serological status to VL using IFAT. The sample composed of 96 pupils (53 males and 43 females) aged 6-11 years. Blood drops were collected on whatman No. 3 filter paper for the serological test (IFAT). Positive reaction was obtained in 6.2% of the examined pupils. The positivity rate was insignificantly higher among the age group (8-10) years. Sex proved to have no effect on the percentage of positive reactors. PMID- 1296976 TI - Cryptosporidium infection among primary school children in a rural area in Alexandria. AB - The present study was carried out on primary school children of both sexes to determine Cryptosporidium infection among them. A sample of 222 was randomly chosen. Their ages varied between 6 and 11 years. The required information as age, sex, socio-economic and environmental data, were collected through a designed questionnaire sheet. Stool samples were collected and examined, using Sheather's sugar solution and subjected to modified Ziell Neelsen stain. The results obtained revealed that, the prevalence rate of the infection was 13.51% among the examined pupils, with highest peak among the age group (6-8) years. No significant relation was found between sex and infection. There was a significant relation between infection and low socio-economic level. Also a significant relation was obtained between the infection and the presence of pets, livestock and animal's shed inside the house. A significant percentage of the infected pupils, were having a close contact with the soil through playing around the houses and in the field. The results revealed that a significant percentage of the infected children had diarrhoea. PMID- 1296977 TI - Effect of processing on availability of essential amino acids in rice flour and cooked rice. AB - The availability of nitrogen, lysine and nine essential amino acids was determined in rice flour and cooked rice. Lysine availability was determined by the growth response method using regression analysis of body weight gain or moisture gain against lysine consumed from rice flour and cooked rice. The results show a good correlation between lysine consumed and weight gain or moisture gain (r = 0.86 + 0.8) for rats fed cooked rice and fair correlation for those fed rice flour. The results of lysine availability show that cooking increases availability by both ways of calculation. The availability of nitrogen and of essential amino acids was also determined by the balance trial method with rats. Results of balance trial show that cooking has no significant effect on essential amino acids availability. Data for weight gain, food efficiency and PER were significantly decreased by cooking. PMID- 1296978 TI - Characteristics of 1,3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2-((S)- lysyloxy)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate, in absorption and excretion in rats and rabbits. AB - The absorption and excretion of 1,3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2- ((S) lysyloxy)propane dihydrochloride (N-556), which is a prodrug for the oral delivery of disodium cromoglycate (DSCG), were studied in rats and rabbits. In both animal species, the plasma concentration of DSCG after oral administration of N-556 peaked within 1.0 h, and thereafter declined with a half-life of about 1.2 h in rats and rabbits. The area under the plasma DSCG level versus time curve (AUC) increased in proportion to the dose of N-556 in both animals. The bioavailability of N-556 as calculated from AUC was about 6% in rats and 40% in rabbits, whereas that of DSCG was only 0.1% in rats and 2.5% in rabbits. About 2% and 15% of the dose were respectively excreted as DSCG in the urine and bile after the oral administration of N-556 in rats. The ratio of biliary excretion to urinary excretion (B/U) after the oral administration of N-556 was about twice that after the intravenous injection of DSCG. In rabbits, the urinary and biliary excretions of DSCG after oral administration of N-556 were about 25% and 5%, respectively. The B/U ratio after the oral administration of N-556 in rabbits was similar to that after intravenous administration of DSCG. The difference in the systemic bioavailability of N-556 between rats and rabbits thus appears to be due to a first-pass effect, in addition to a difference in the absorption rate. PMID- 1296980 TI - Methylprednisolone reduces the nephrotoxicity caused by cisplatin. AB - Male Sprague-Dawley rats were given either 6.5 or 8.5 mg/kg of iv cisplatin combined with three injections of sc methylprednisolone in doses of either 50, 100 or 250 mg/kg at -4, 0 and 4 h after the cisplatin injection. Blood urea nitrogen and serum creatinine levels were determined on day 5 following the cisplatin injection. The protective effects of methylprednisolone on cisplatin induced nephrotoxicity were clearly demonstrated. Our preliminary results suggest that a much higher dose of cisplatin could be injected in cancer chemotherapy, if it was combined with methylprednisolone. PMID- 1296979 TI - Effects of nanomolar to submillimolar carteolol on noradrenaline release in the absence and presence of uptake1 and uptake2 blockers in guinea pig pulmonary arteries. AB - Effects of nanomolar to submillimolar carteolol, a non-selective beta-antagonist, on the evoked release at 1 Hz and the spontaneous release in the absence and presence of uptake1 and uptake2 blockers were studied in pulmonary arteries, isolated from guinea pigs, and then preloaded with [3H]noradrenaline. dl Carteolol at 10(-8), 10(-7) and 10(-6) M applied at the increasing concentrations inhibited the evoked [3H]-release in untreated arteries and in desipramine and corticosterone-treated arteries. The spontaneous [3H]-release slightly but significantly increased or tended to increase in untreated arteries. dl-Carteolol at 10(-5) and 10(-4) M clearly and concentration-dependently increased the spontaneous [3H]-release in untreated and cocaine-treated arteries. This increase was markedly inhibited by further pretreatment with normetanephrine. The evoked [3H]-release was not altered by dl-carteolol at 10(-5) M, but increased at 10(-4) M. This increase was not modified by cocaine and by cocaine and normetanephrine. d-Carteolol at 10(-5) and 10(-4) M produced effects similar to those of dl carteolol. Nanomolar to micromolar dl-carteolol inhibits the evoked [3H]-release, which supports our previous conclusion that this inhibition is due to blockade of tonically functioning presynaptic beta 2-adrenoceptors. Carteolol at the higher concentrations seems to become a substrate for an uptake2 mechanism and to produce an unknown sympathomimetic activity in guinea pig pulmonary arteries. PMID- 1296981 TI - The effect of dietary changes and intentional weight loss on high density cholesterol levels in older adults. AB - The effect of a behaviorally-oriented program to reduce calories and increase physical activity on HDL cholesterol level was evaluated in overweight older adult subjects (n = 31). HDL cholesterol increased from 45.8 to 52.1 mg/dl (p < .0003), and total mean cholesterol increased from 238.0 to 249.5 mg/dl (p < .05). Body weight decreased from 175.0 lbs to 172.6 lbs (p < .03). Analysis of baseline and 40 week food frequency questionnaires indicated that the mean caloric intake had decreased from 1535 to 1303 kcal/day (p < .02), and total fat intake decreased by 9.8 gm/day (p < .01). Weight loss accounted for 13% of the variance in HDL cholesterol change (p < .05). Decreasing fat intake resulted in a smaller increase in HDL cholesterol (F, (1,29) = 5.91, p < .03). Our findings provide further support that a prudent approach to weight reduction can be beneficial in an older adult population. PMID- 1296982 TI - Satisfaction of senior citizens in a nutrition education program with and without computer-assisted instruction. AB - This study assessed the receptiveness of senior citizens to the use of microcomputers in a nutrition education program at participating senior citizen subsidized housing sites. Participants in group A received the nutrition education program with computer-assisted instruction (CAI). Group B participants received the same nutrition education program, but without CAI. A validated Program Satisfaction Questionnaire was administered to assess overall satisfaction, satisfaction with the method of instruction, and satisfaction with the dietary analysis printout. Independent t-test analysis showed that group A was as satisfied as group B. The majority in group A indicated that learning to use the computer was not difficult and was "somewhat enjoyable" to "very enjoyable." These results indicated that senior citizens were receptive to CAI. Additionally, the use of the microcomputer with older adults was deemed possible for health-related educational programming. Appropriate modification of software was recommended to meet the physical limitations which occur with this age group. PMID- 1296983 TI - Food habits and nutritional knowledge of Portuguese participants in an elderly nutrition program. AB - Massachusetts has the largest population of immigrant Portuguese in the United States, yet few elder service programs specifically designed to meet their needs exist. Therefore, a special nutrition program was developed in Somerville, Massachusetts to provide culturally appropriate lunches twice a week, followed by socialization activities. A survey of the participants showed that only 11% of respondents met recommended intake of dairy, protein, fruits and vegetables, as determined by the Basic Four Scoring System. The most frequently lacking food among the remaining participants were fruits and vegetables, followed by grains, as well as dairy products. The recommended protein intake was met by all but two respondents. The majority of respondents were able to identify a high sodium food, a food high in Vitamin C, a nutritionally balanced meal, and identified calcium as a necessary nutrient throughout the lifespan. Fewer respondents were able to identify foods high in protein, high in calories, and high in fiber, although their diets contained substantial amounts of these nutrients. PMID- 1296984 TI - Living with "OBRA". PMID- 1296985 TI - Multivariate analysis of dietary habits in 931 elderly Japanese males: smoking, food frequency and food preference. AB - To define the influence of smoking on dietary patterns and food preference in elderly Japanese, a mail survey was conducted on about 3000 subjects aged 65 years and older. A multivariate analysis of dietary frequency data regarding 15 food items on 931 male respondents suggested that frequency of intake of plant food, including vegetables and fruits, was lower in smokers than in nonsmokers. Another multivariate analysis of food preference data regarding 18 food items on the same subjects suggested that smoking decreased the desire for plant food. PMID- 1296986 TI - Dietary changes reported by a random sample of elderly people. AB - A random sub-sample of 153 elderly people was followed up 18 months after a large scale random dietary survey of adults aged 65 years and over residing in Adelaide, South Australia. The follow-up questionnaire examined self-reported dietary and weight change over the 18 month period since the original study. The same semi-quantitative food frequency questionnaire as used in the initial survey was also repeated. Challenging the common stereotype of rigidity and resistance to change in elderly people, a high degree of dietary change was reported since the original study (67% of men and 68% of women reported a change in diet), particularly among the 65-69 year age group (78%). The most commonly reported changes were largely in accord with dietary guidelines. Commonly reported changes included less frequent intake of red meat, eggs, fried and fatty foods and more frequent intake of vegetables, chicken and fish, as well as changes towards use of polyunsaturated margarine, no longer eating the fat on meat and no longer presoaking vegetables in water before cooking. Of concern was a change in some subjects to a less frequent consumption of milk or other dairy products. PMID- 1296987 TI - Positive effect of a nutrition instruction model on the dietary behavior of a selected group of elderly. AB - The effectiveness of the Nutrition Instruction Model to promote a positive change in the dietary behavior in a selected group of the elderly was tested. Subjects were one hundred and four adults, aged 65 and over, who were assigned to three groups. The experimental group received nutrition education based on the components of the model. The other two groups received nutrition education via the lecture approach or no intervention. The experimental subjects showed the greatest positive dietary behavior change. The study results suggest that the Nutrition Instruction Model may be effective in leading to dietary behavior change in the elderly. PMID- 1296988 TI - Dietary aluminum and Alzheimer's disease. AB - Aluminum accumulation has been implicated in the development of Alzheimer's Disease, a hallmark of which is decreased brain glucose metabolism. Dietary sources of aluminum include that which comes from the contact of food with aluminum cook ware, containers, foil, and utensils. Normal aluminum intake from all sources is estimated as 12-14 mg per day. We have evaluated brain glucose metabolism in the presence of physiologically achievable levels of aluminum, in the range 10(-15) to 10(-5) M. Our results indicate no effect of aluminum in the range tested. Thus the contact of food with aluminum cooking utensils cannot alone raise plasma aluminum concentrations to the millimolar levels required to decrease brain glucose metabolism. Non dietary pathophysiological mechanisms are operating which lead to the accumulation of tissue aluminum, since most of dietary aluminum is excreted by the kidney. PMID- 1296989 TI - Cardiovascular drugs for the medically indigent. A report to primary care physicians on pharmaceutical companies' service. PMID- 1296990 TI - Improving accuracy of death certificates. PMID- 1296991 TI - Health-care reform: NMA's vision. PMID- 1296992 TI - Tuberculosis prevention project. AB - This article reports the findings from a clinical study that examined the impact of health education and counseling on the decision of a patient infected with tuberculosis (TB) to complete a regimen of isoniazid (INH) chemoprophylaxis for 6 months to prevent TB. Forty patients were divided into two groups; both groups were administered a questionnaire to collect demographic data and medical history. One group received additional health education and counseling independent of clinic staff, and the other group only received health education and counseling from clinic staff. The proportion of patients in the first group who completed INH for 6 months (63.6%) was significantly greater than the proportion of patients in the second group (11.1%). These findings suggest that health education and counseling did make an impact on the decision of a patient infected with TB to conform with a rational choice when provided with information and a supportive relationship about the consequences of TB infection. PMID- 1296994 TI - Drug resistance in malaria: a review of the west African situation. AB - Chloroquine-resistant Plasmodium falciparum malaria is an emerging problem in the West African subregion. While chloroquine remains an effective antimalarial agent in some countries of West Africa, the susceptibility patterns of P falciparum strains need to be assessed periodically. This article reviews the literature on chloroquine-resistant P falciparum malaria. PMID- 1296993 TI - Risk factors for infection in the trauma patient. AB - The most common cause of late death following trauma is sepsis. The traumatized patient has a significant increased risk of infection. Transfusion, hypotension, and prolonged ventilatory support are predictive of septic complications. In addition, the trauma patient has a higher predisposition to pneumonia than nontrauma patients (18% versus 3% incidence of pneumonia, P < .001). Additional risk factors include the degree of nutrition status and the type of medications used during surgery. Immunologic depression may be an additional risk factor. There is mounting evidence that trauma can result in host defense abnormalities. To prevent the significant mortality caused by sepsis, close surveillance must be maintained, nutritional status must be optimal, and liberal use of antibiotics should be discouraged. Their use should be guided by appropriate cultures and sensitivities. PMID- 1296995 TI - Cough requiring discontinuance of angiotensin-converting enzyme inhibitors in an urban inner-city population. AB - Angiotensin-converting enzyme (ACE) inhibitors are increasingly used to control hypertension although cough, sometimes severe enough to require discontinuance, is a well-described side effect of these drugs. Manufacturers' labeling indicates that this side effect occurs with a much lower frequency than is reported in the literature. This article describes the incidence of cough as a side effect of ACE inhibitors in a small inner-city practice and presents two reports of patients who required discontinuance of ACE inhibitors for this symptom. It is suggested that, consistent with the recent literature, the incidence of this symptom is more frequent than suggested by manufacturers' labeling, at least in this population. PMID- 1296996 TI - Psychiatric deinstitutionalization and its cultural insensitivity: consequences and recommendations for the future. AB - Despite the plethora of models and strategies for addressing issues that surround the chronically mentally ill, there remains a paucity of literature that addresses the specific implications of deinstitutionalization on racial minorities. Racial minorities comprise a significant number of the homeless, jailed, and geriatric mentally ill. History and current reality suggest the reasons why some chronically mentally ill blacks and their families have feared the impact of deinstitutionalization. This article examines the Ohio State Department of Mental Health's response to these issues as a possible prototype for statewide coordination for deinstitutionalization. PMID- 1296997 TI - Leukocyte count and cardiovascular risk factors. AB - In view of the growing evidence for leukocyte count as an important cardiovascular risk factor, data from the first National Health and Nutrition Examination Survey (NHANES I) were examined to determine the association of leukocyte count with a number of other cardiovascular risk factors. Complete data were available for 5586 persons. Multiple linear regression analyses revealed hemoglobin concentration and height in white male nonsmokers and hemoglobin, cigarettes/day, and pulse rate in white male smokers were associated with leukocyte count. In white female nonsmokers, age, pulse rate, systolic blood pressure, height, and uric acid concentration were associated with leukocyte count. In white female smokers, hemoglobin, cigarettes/day, pulse rate, and height were associated with leukocyte count. However, associated variables explained only 8% of the variation in leukocyte count. Other measured risk factors were not associated with leukocyte count. Future analyses of leukocyte count and cardiovascular disease should control for hemoglobin concentration and pulse rate in addition to smoking, blood pressure, and cholesterol. PMID- 1296998 TI - Use of lithium in maintaining T-cell functions in persons with documented acquired immunodeficiency syndrome. AB - This article presents two patients with human immunodeficiency virus who were treated with lithium and describes the possible effect the lithium may have had on their T-cell systems. PMID- 1296999 TI - Mandibulofacial dysostosis (Treacher Collins syndrome): a case report. AB - Mandibulofacial dysostosis, also known as Treacher Collins syndrome, is a rare congenital anomaly that must be identified in infancy to prevent irrevocable developmental impairment. Information is sparse in the current medical literature concerning this rare syndrome. This article reports a case of Treacher Collins syndrome with the presence of a scarring alopecia and acne keloidalis nuchae, which are possibly coincidental symptoms, but have not been previously described clinically in this malady. PMID- 1297001 TI - Annual reporting of hospital mortality rates for Medicare patients--racial aspects. PMID- 1297000 TI - Suppurative sinusitis in critically ill patients: a case report and review of the literature. AB - Nosocomial sinusitis is occasionally overlooked as a source of sepsis in critically ill patients. Physical examination is usually unreliable and purulent nasal discharge is absent up to 73% of the time. Computed tomography scans of the sinuses and aspiration and culture of sinus fluid are the hallmark of diagnosis. Therapy consists of removal of tubes and packing, appropriate antibiotics, and drainage. Risk factors for nosocomial sinusitis include nasotracheal tubes, nasogastric tubes, prior steroid and antibiotic therapy, and facial fractures. This article reports a case of suppurative sinusitis following prolonged intubation and reviews the literature. PMID- 1297002 TI - High prevalence of hepatitis C virus infection in aborigines in Taiwan. AB - In Taiwan, the epidemiological status of HCV infection is similar to those observed in other areas of the world, with 1.0% prevalence among adult volunteer blood donors and high prevalences among the high risk groups, by the detection of anti-HCV with synthetic peptide antigens. However, unusually high prevalences, 35.1%, 15.8% and 14.2%, were observed among adult populations in three of the five aboriginal communities. No difference in sex specificity was noted. In 37 (75.0%) of the 48 anti-HCV-positive cases, HCV-RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) assay. None of such particular risk factors as tattooing, sexual promiscuity, operation, blood transfusion, nor intravenous drug abuse could be accounted for this high prevalence of HCV infection. No helpful supporting evidence for ethnic specificity was noted, either. Although a possible sexual transmission between spouses was observed, it is unlikely to be the main cause of the high prevalence in these aboriginal communities. We conclude that the unusually high prevalence of HCV infection observed in some aboriginal communities in Taiwan could be ascribed to poor anti septic medical practice derived from insufficiency of medical personnel and facilities in these communities as compared with the other regions in Taiwan at the time before twenty years ago. PMID- 1297004 TI - Metallothioneins in spontaneously hypertensive rat liver. AB - The metallothionein (MT) synthesis was induced in the liver of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats through sc injections of CdCl2 for 3 and 6 days. The MT contents of the liver of these animals and of untreated rats from both groups were determined by gel filtration, HPLC, SDS/PAGE and amino acid analysis. The isoforms MT1 and MT2 were identified and their Cd, Zn and SH-group contents were determined. The SHR showed significantly higher values of MT than WKY rats in the untreated animals and on the 3rd day of the induction. On the 6th day, the MT levels in both groups were equal. The Cd and Zn contents followed the MT concentration in the homogenates. The possible relation between the arterial hypertension and the zinc and copper homeostasis is discussed. PMID- 1297003 TI - Epidemiological study of malaria in north Sulawesi, Indonesia by fluorescence and Giemsa staining. AB - An epidemiological study of malaria infection was conducted in the Likupang District, Minahasa Regency, North Sulawesi Province, Indonesia, during August 2 15, 1991. In this study, 510 people of six villages, representing ages between 1 month to 84 years cooperated voluntarily. Blood smears stained with Giemsa and acridine orange (AO), revealed 33 and 83 malaria parasite positives respectively. This significant difference was due particularly to the fact that AO staining examined under either a daylight- or halogen-illuminated microscope equipped with interference filters was sensitive to detect low-density parasitemia in many subjects previously diagnosed negative by Giemsa staining in the field. The low malaria prevalence obtained by Giemsa staining may have been attributable to the lack of standard-quality diagnostic tools in the field or inadequate observation of the slides. In both staining methods, Plasmodium falciparum was found to be the predominant species, while the remainings were P. vivax or a mixture of both. Subjects infected with P. vivax revealed higher density of parasitemia and gametocytemia than those with P. falciparum. PMID- 1297005 TI - Immune response to Echinococcus multilocularis infection in the mouse model: a review. AB - Echinococcus multilocularis is a cestode helminth which, along with E. granulosus, E. oligarthus and E. vogeli is a causative agent of hydatid disease in man. In the intermediate host (including man), cysts formed by the metacestode (larval stage) develop in the internal organs, causing functional impairment which often leads to the death of the host. In this review larval E. multilocularis infection in mice, the most popular experimental intermediate host, is examined, and the immune response to the organism is described in detail. Evidence is presented which suggests that cell-mediated immunity (CMI) plays a large role in suppression of larval growth. Congenitally athymic nude mice, and mice treated to remove thymocytes had high susceptibility to infection, while mice strains assessed as having high helper T lymphocyte function showed resistance to infection. The degree of antibody response shown by the host does not correlate with the susceptibility to E. multilocularis. Infection with E. multilocularis is accompanied by immunosuppression, manifested by inhibition of effector cell chemotaxis and receptor expression, suppressor macrophage and lymphocyte activity, decline in helper T-lymphocyte activity and immune-complex deposition. PMID- 1297006 TI - The relationship between reduced glutathione level and glutathione S-transferase activity in sheep erythrocytes. AB - The relationship between reduced glutathione (GSH) level and glutathione S transferase (GST) activity in erythrocytes was examined, using sheep erythrocytes, which have varying GSH concentrations, and dog erythrocytes with an inherited high concentration of GSH. There was a positive correlation (r = 0.529, p < 0.001) between the GSH level and GST activity in sheep erythrocytes. In dog erythrocytes, the GST activity in high-GSH cells was significantly (p < 0.001) higher than that in normal-GSH cells. These results indicate that the activity of GST in erythrocytes is directly correlated with the intracellular GSH level. PMID- 1297007 TI - Catarrhal proventriculitis associated with a filamentous organism in pet birds. AB - Catarrhal proventriculitis due to infection by an unidentified organism was diagnosed in 79 of 534 pet birds examined histologically. It was more prevalent in domestic birds (70 cases) than in imported ones (9 cases). A high incidence of the disease was encountered in budgerigars (Melopsittacus undulatus) and it was occasionally found in finches (Poephila gouldiae gouldiae), parakeets (Psittacula Krameri manillensis), Amazona parrots (Amazona aestiva aestiva) and cockatiels (Nymphicus hollandicus). The agent was a large filamentous rod, and was stained positively with Gram, GMS and PAS methods. Histologically, it induced a mild to moderate exudative or proliferative inflammation in the proventriculus. All the cases had an erosion in the gizzard. Ultrastructurally, the organism had a eukaryotic nucleus and three cell-wall layers. Concurrent infections were very common, including adenoviruses (37 cases), giardiasis (31 cases), candidiasis (13 cases), papovaviruses (11 cases) and knemidocoptic mites (11 cases). PMID- 1297008 TI - Development of mouse embryonic nuclei transferred to enucleated oocytes and zygotes. AB - The present study was conducted to examine the development of nuclear transplant embryos produced by transplanting nuclei to either oocytes or zygotes in the mouse. Metaphase II oocytes and one-cell zygotes were enucleated and fused with transferred nuclei from late two-, four- and eight-cell stage embryos. Enucleation of metaphase oocytes was achieved using the interference microscope without staining. Fusion and oocyte activation were performed by means of electric fields. Similar development rates to the blastocyst stage were obtained from enucleated oocytes (28.0%) and zygotes (30.9%) reconstituted with nuclei from late two-cell embryos. Cleavage and blastocoele formation of reconstituted embryos occurred at around the same time as observed in the control embryos, with some exceptions. After transfer to recipient females, live young were obtained from both reconstituted oocytes (9.1%) and zygotes (11.5%) that received a nucleus from late two-cell embryos. The results indicate that enucleated zygotes as well as oocytes can support development to term of nuclei introduced from late two-cell embryos in which activation of the embryonic genome has occurred, which may be a result of the reprogramming of the donor nucleus. PMID- 1297009 TI - Histopathological survey of protozoa, helminths and acarids of imported and local psittacine and passerine birds in Japan. AB - A total of 534 psittacine and passerine birds consisting of 241 imported and 293 local birds were examined histologically. As a result, the following parasites were found: Giardia (86 cases), Knemido-coptes (26 cases), coccidia (10 cases), Ascaridia (6 cases), Cryptosporidium (5 cases), Sarcocystis (5 cases), tapeworm (4 cases), microfilaria (2 cases), Hexamita (1 case), and Spiroptera (1 case). High incidences of giardiasis and knemido-coptic infestation were detected in the local birds, but rarely in the imported birds. Giardial trophozoites were observed mainly in the duodenum of budgerigars (Melopsittacus undulatus). Knemidocoptic mites burrowed into the epidermis producing proliferative dermatitis in 25 budgerigars and 1 African Grey Parrot (Psittacus erithacus erithacus). This ectoparasite often infested the skin around the cloaca. Coccidiosis was seen only in the small intestines of the finch (Poephila gouldiae gouldiae), African Grey Parrot, Rainbow lory (Trichoglossus haematodus), Indian Ring-necked parakeet (Psittacula krameri manillensis) and peach-faced lovebird (Agapornis roseicollis). Two parrots (Amazona aestiva aestiva and Psittacus erithacus erithacus) and two budgerigars had intestinal cryptosporidiosis. Conjunctivitis associated with cryptosporidial infection was seen in a lovebird. Sarcocystis cysts containing crescent-shaped bradyzoites were found not only in the thigh and breast but also in the heart and cloacal muscles. Other organisms such as Ascaridia, tapeworm, microfilaria, Hexamita, and Spiroptera were clinically less significant. However, infections such as Giardia and Cryptosporidim might have zoonotic implications. PMID- 1297010 TI - Effect of radiographic landmark identification errors on the accuracy of three dimensional reconstruction of the human spine. AB - In three-dimensional reconstruction of the human spine obtained from stereo radiographic set-ups (two radiographs or more), it is extremely difficult to identify exactly the same landmarks on all radiographs. The effect of these identification errors was investigated with simulations made on points of known three-dimensional co-ordinates and compared with three-dimensional reconstructions of real spines obtained with the direct linear transformation algorithm. Results showed that radiographic identification errors of up to 2 mm were common, causing reconstruction errors of up to 5 mm. These reconstruction errors may be noticed in the form of geometrical inaccuracies in the graphical representation of three-dimensional reconstructions of the spine. Successive displacements were then imposed on image point co-ordinates to minimise the identification error and increase the reconstruction accuracy. The improvement on the three-dimensional reconstruction results was negligible. Three-dimensional reconstructions obtained from three radiographs were also investigated. They showed slightly more accurate reconstructions than those obtained from two radiographs. However, the increase of X-ray exposure on the patient may not be worthwhile. PMID- 1297011 TI - Segmentation, modelling and reconstruction of arterial bifurcations in digital angiography. AB - The paper presents a method to model an arterial bifurcation from a pair of X-ray angiographic images. It is the initial step of a reconstruction process aiming at detecting and quantifying abnormal sites located on bifurcations. The method proposed consists of two steps. First, each image is independently segmented to extract the vessels in the images. The algorithm uses dynamic programming first to find the bifurcation centrelines from the original images, and secondly to extract vessel edges from the morphological gradient images, under a constraint of parallelism with the previously detected centrelines. Then, a three dimensional bifurcation model is built by adapting cylinders around the three dimensional bifurcation centrelines. These cylinders are obtained as a stack of binary orientable ellipses fitted to the projection densities in the corresponding cross-sections. Results obtained on simulated data, phantom and femoral bifurcations are displayed. PMID- 1297012 TI - ECG data compression by corner detection. AB - An ECG sampled at a rate of 360, 500 samples s-1 or more produces a large amount of redundant data that are difficult to store and transmit. A process is therefore required to represent the signals with clinically acceptable fidelity and with the least code bits possible. In the paper, a real-time ECG data compressing algorithm, CORNER, is presented. CORNER is an efficient algorithm which locates significant samples and at the same time encodes the linear segments between them using linear interpolation. The samples selected include, but are not limited to, the samples that are significantly displaced from the encoded signal such that the allowed maximum error is limited to a constant epsilon which is specified by the users. The way in which CORNER computes the displacement of a sample from the encoded signal guarantees that the high activity regions are more accurately coded. The results are compared with those of the well known data compression algorithm, AZTEC, which is also a real-time algorithm. It is found that, under the same bit rate, a considerable improvement of the signal-to-noise ratio (SNR) and root mean square error (RMSerr) can be achieved by employing the proposed CORNER algorithm. An average value of SNR (RMSerr) of 27.0 dB (5.668) can be achieved even at an average bit rate of 0.79 bit sample-1 by employing CORNER, whereas the average value of SNR (RMSerr) achieved by AZTEC under the same bit rate is 16.60 dB (19.368). PMID- 1297013 TI - New signal processing techniques for the decomposition of EMG signals. AB - This paper relates to the use of knowledge-based signal processing techniques in the decomposition of EMG signals. The aim of the research is to automatically decompose EMG signals recorded at force levels up to 20 per cent maximum voluntary contraction (MVC) into their constituent motor unit action potentials (MUAPS), and to display the MUAP shapes and firing times for the clinician. This requires the classification of nonoverlapping MUAPs and superimposed waveforms formed from overlapping MUAPs in the signal. Nonoverlapping MUAPs are classified using a statistical pattern-recognition method. The decomposition of superimposed waveforms uses a combination of procedural and knowledge-based methods. The decomposition method was tested on real and simulated EMG data recorded at force levels up to 20 per cent MVC. The different EMG signals contained up to six motor units (MUs). The new decomposition program classifies the total number of MUAP firings in an EMG signal with an accuracy always greater than 95 per cent. The decomposition program takes about 15s to classify all nonoverlapping MUAPs in EMG signal of length 1.0s and, on average, an extra 9s to classify each superimposed waveform. PMID- 1297014 TI - Comparison of the histochemical and contractile properties of human triceps surae. AB - The purpose of the study was to compare the contractile properties determined from an electrically stimulated twitch with histochemically determined fibre type parameters of the human triceps surae. Muscle samples were obtained from the medial head of the gastrocnemius of ten male athletes. Ages ranged from 20 to 29 years. Muscle samples from the belly of the medial gastrocnemius muscle were obtained using the needle biopsy technique. The samples were treated histochemically for myosin ATPase to classify the fibres as either slow twitch (ST) or fast twitch (FT) and to determine fibre areas. Surface electrical stimulation was used to determine muscle twitch parameters. The contractile variables of the muscle twitch were latency (L), time to peak force (TPF), peak force (PF), half-contraction time (1/2 CT) and half-relaxation time (1/2 RT). Backward elimination procedures for dependent variables were used to determine which contractile properties best represented the histochemical profile of the muscles. Prediction formulas were developed for FT and ST percentages (R2 = 0.98, p < 0.001), relative area percentage (R2 = 0.87, p < 0.001), and ST area (R2 = 0.85, p < 0.01). It was concluded that the use of the electrotensiometer (ETM) protocol was a valid testing procedure when studying physiological relationships of histochemical properties in intact human skeletal muscle. PMID- 1297016 TI - Heart position and orientation in forward and inverse electrocardiography. AB - A study has been made of the influence of the position and orientation of the heart within the thorax on computed ECG waveforms (forward model) and on computed activation sequences (inverse model) in three normal cases. Results show that differences in heart position and orientation, associated with shifts relative to the precordium of the order of 0.5 cm, may result in amplitude differences or QRS waveforms of typically tenths or millivolts, which constitute part of the observed interindividual variability of the ECG. The inverse study shows that, in spite of similar errors in estimated heart position and orientation, stable solutions of the ventricular activation sequence can still be found. However, in the case where the heart is very close to precordial leads, the stability of the inverse solution is found to be intrinsically poor. PMID- 1297015 TI - Theoretical analysis of the relationship between the ratio of ventricular systolic elastance to diastolic stiffness and stroke volume. AB - The maintenance of adequate blood circulation requires a sufficient ventricular contractility; in addition, to eject blood, the ventricles must first receive a sufficient volume, requiring a low diastolic stiffness. A simplified cardiovascular model was used to derive formulae for stroke volume (SV) as a function of atrial pressure and the ratio of ventricular end-systolic elastance to end-diastolic stiffness. A more complex cardiovascular model was used to assess the ability of the expressions to predict stroke volume under various steady-state conditions. The predicted SV correlated linearly with the model SV over a wide range of diastolic stiffnesses and systolic elastance. The formulae predict that with fixed right atrial pressure the SV is proportional to the ratio of end-systolic elastance to end-diastolic stiffness (GR) for the right ventricle, but relatively insensitive to the ratio (GL) for the left ventricle provided that GL is greater than GR. Model simulations confirmed this. When the right atrial pressure was not fixed increases in GR with fixed GL reduced the right atrial pressure with little change in SV. Similarly, varying GL with fixed GR produced little change in SV. The ratios highlight the importance of diastole to cardiac function. PMID- 1297017 TI - Test of four defibrillation dosing strategies using a two-dimensional finite element model. AB - The most widely used defibrillation dosing strategy is that adopted by the American Heart Association in 1986. However, several alternative dosing strategies have been proposed to match delivered energy to the individual requirements of defibrillation subjects. In this study, two-dimensional finite element methods are used to investigate the performance of four of these dosing strategies applied to three thoracic models representative of men and women of different thoracic aspect ratios. From the resulting current density distributions, the relative effectiveness of the following dosing strategies are evaluated and compared: constant current; current proportional to body weight; constant energy; energy proportional to body weight. Our results show that the strategy of applying current proportional to subject body weight with a current dose of 0.58 A kg-1 was able to defibrillate all three subjects with only minimal overexposure of any one of them. None of the other dosing strategies examined could be made to successfully defibrillate all three subjects without significantly overexposing at least one. PMID- 1297018 TI - In vitro performance test system for pulse oximeters. AB - An in vitro system was developed capable of testing the accuracy and reproducibility of pulse oximeter readings. The pulse oximeter probe receives signals through a pulsating blood cuvette. The development of the design of the cuvette is described. Using the final design (or 'model finger'), a comparison is made between readings from a Datex Satlite pulse oximeter (SpO2) and saturation values obtained by use of a multi-wavelength bench oximeter (SaO2). Linear regression analysis of the data gives SpO2 = 0.88 SaO2 + 11.2 (r = 0.979, p < 0.001). PMID- 1297019 TI - Electric conductivity of stationary and flowing human blood at low frequencies. PMID- 1297021 TI - Audiometry environment remote control system. PMID- 1297020 TI - Time and frequency analysis of EMG signals of homologous elbow flexors and extensors. PMID- 1297022 TI - Evidence of changes in regional blood perfusion in human intracranial tumours during conductive interstitial hyperthermia. PMID- 1297023 TI - Computer-controlled in vitro model of the human left heart. AB - The decision for surgical intervention in the treatment of stenosis and for regurgitation of the mitral valve demands an objective and quantitative evaluation of the severity of mitral valve disease. The availability of ultrasound techniques capable of analysing flow velocities across valves and to produce representative images of valve orifices has increased the interest in the hydraulics of cardiac valves. To isolate and study the determinants of transmitral flow, an in vitro model of the human left heart was built. From the model it is possible to differentiate the influence of the different determinants of left heart performance on transmitral flow: preload, compliance of the left atrium and ventricle, peripheral resistance (afterload) and heart rate. The mechanical part of the model consists of a reservoir connected to an elastic closed circuit (Latex pulmonary veins, left atrium, left ventricle and aortic arch) with replaceable mitral and aortic valves. The electronic part of the model drives and controls the hydraulic part, allowing the independent regulation and monitoring of left atrial and left ventricular pressures p, volumes V and 'pV loops' throughout the cardiac cycle at different cardiac rhythms. Left atrial filling pressure and aortic resistance are variable in a controlled fashion. Echo Doppler study of the mitral valve and the transmitral valve flow is possible both from an atrial and a ventricular window in the model. This technical note describes the model. PMID- 1297024 TI - Radio telemetry directional ultrasonic blood flowmeter for use with unrestrained animals. PMID- 1297025 TI - Mouse emulator for tetraplegics. PMID- 1297026 TI - Measurement of gait by accelerometer and walkway: a comparison study. PMID- 1297027 TI - Standard algorithm of blood-pressure measurement by the oscillometric method. PMID- 1297028 TI - [Evaluation of usefulness of the PYR-Wellcome test for identifying microorganisms from the genus enterococcus]. AB - The study was aimed at evaluation of usefulness of PYR-Wellcome test in bacteriological diagnostic. Results of identification of enterococcal strains by application of the above test were performed on 157 strains of Enterococcus spp., 15 strains of Streptococcus pyogenes and 12 of Streptococcus bovis. Application of test for PYR-ase production results in shortening of diagnostic procedure. Basing on morphological features, including type of hemolysis, lack of catalase production and presence in the bacterial cell of a peptidase hydrolyzing L pirrolidonyl-beta-naphthylamide, it is possible to classify with high probability the investigated microorganism to the Enterococcus spp. The Shortened procedure is satisfactory for routine identification of enterococcal strains in diagnostic laboratories. PMID- 1297029 TI - [occurrence of mannose- resistant adhesins MRHA in E.Coli strains isolated from children with diarrhea]. AB - The study was aimed at determination of the frequency of occurrence of mannose resistant adhesins in E. coli strains isolated from children with diarrhoea. It was also of interest whether their presence is associated with the serological type or other virulence factors. The material used in this study consisted of 1022 strains of E. coli (EPEC, ETEC and EIEC) and 3431 isolates from sick children and 960 from healthy children (non-EPEC-ETEC-EIEC). Enterotoxigenicity and entero-invasiveness of strains was evaluated by biological tests performed on animals and in tissue culture. Production of MRHA adhesins was determined by the test of mannose-resistant active hemagglutination, and of colonization factors antigens CFA by application of agglutination and agar gel immunodiffusion tests. Most frequently MRHA adhesins were produced by ETEC strains-80% of strains. All of them appeared to be a colonization factor antigen CFA/I. EPEC strains produced various MRHA adhesins only by 12.6% of strains. Production of MRHA adhesins by EIEC strains was not detected. Frequency of occurrence of MRHA adhesins in E. coli strains which were non-EPEC-ETEC-EIEC was dependent from the isolation source. MRHA adhesins were most frequently found in strains isolated from sporadic cases of light diarrhoea in ambulatory treated children (49%), much less among isolates from children hospitalized because of severe diarrhoea (33%), and from healthy children in 9% of isolates only. These results may indicate the potential role of MRHA adhesins in pathogenesis of diarrhoea in children. PMID- 1297030 TI - [A strain of Aeromonas veronii isolated from a patient suspected of cholera]. AB - Investigations were carried on a strain isolated from patient hospitalized in Poland. The patient returned from Odessa, a region with cholera epidemic. The strain was suspected to be Vibrio cholerae, but it did not agglutinate in V. cholerae 01 serum. The aim of this study was establishment of taxonomical classification of this strain, in order to demonstrate whether it is a representative of the non-cholera vibrio group (not agglutinating) or another representative of the family Vibrionaceae. The strain was resistant to bile salts in TCBS medium and demonstrated several properties from a borderline of two Vibrio and Aeromonas species. Its properties were similar to the group of recently described pathogenic vibrio, but it did not require higher concentrations of NaCl in the medium and was resistant to the vibriostatic factor 0/129. These properties were considered as decisive in differentiation of Vibrio and Aeromonas. The strain was finally classified as Aeromonas veronii. It is a first case in Poland of isolation of A. veronii from the feces of patient with cholera-like symptoms. As newly described pathogenic species of genus Vibrio and Aeromonas were not isolated in Poland, we present schemes which may serve for beginning of this type of diagnostic investigations. PMID- 1297031 TI - [The role of bacterial metabolism in transformation of non-mutagenic compounds into mutagens. I. Participation of Escherichia coli nitroreductase in creation of mutagens from non-mutagenic new pesticides]. AB - Investigations concerned Escherichia coli nitroreductase in creation of mutagens from non-mutagenic pesticides-derivatives of urea. Three new compounds were studied: N-phenyl-N'-methylurea (IPO 4328), N-methyl,N-(2-hydroxyethyl) N'phenylurea (IPO 2363), N-(2-hydroxyethyl), N-methyl-N'-(3,4 dichloroethyl) urea, and diurone-3-(3,4 dichlorophenyl)-1,1 dimethylurea. These compounds were incubated in anaerobic conditions with cells of E. coli K-12 (KF) strain and nitrate or nitrite. Using Ames test, mutagenicity of resulting metabolites was investigated. It was found that during incubation of herbicide IPO 4328 with cells of E. coli K-12 (KF) and nitrate, mutagenic product for strain of S. typhimurium TA 1537 is created. Very weak mutagenic metabolite for the same strain was appearing during incubation of herbicide IPO 2363 with cells of E. coli K-12 (KF) in presence of nitrite. Incubation of investigated compounds with E. coli K-12 (KF) cells alone did not result in appearance of mutagenic substances. Thus, role of Escherichia coli in creation of mutagenic compounds from non-mutagenic derivatives of urea consisted of nitrite from nitrate production with participation of nitroreductase, which afterwards in absence of bacteria or action of their enzymes reacted with investigated pesticides. PMID- 1297032 TI - [Role of bacterial metabolism in transformation of non-mutagenic compounds into mutagens. II. Participation of bacteria producing urease in degradation of pesticides--urea derivatives]. AB - Participation of bacteria producing urease: Proteus mirabilis and Staphylococcus epidermidis in degradation of pesticides--urea derivatives, was investigated. Four new compounds were studies: N-/(3-trifluoromethyl)phenyl/N'-(2-cyanoethyl) urea (IPO 6584), N-(4-chlorophenyl)-N'-(2-hydroxyethyl)-N'-ethylurea (PO 6236), N (4-chlorophenyl)-N'-(2-hydroxyethyl), N'-propyl-urea (IPO 6237), N-(2 hydroxyethyl), N-methyl-N'-(3,4 dichlorophenyl)-urea (IPO 3102), pesticide reference standard--thiram fungicide--tetramethyl-bis-thiocarbamyl disulfide, and rodenticide-alpha-naphthylthiourea (ANTU). Investigated compounds were incubated with cells of P. mirabilis 4508 ans S. epidermidis CCM 2448 and commercial preparation of urease from beans. Mutagenicity of resulting metabolites was then studies by the Ames test. All compounds were decomposed by bacteria used in this study, as well with beans urease with different activity. Reaction products did not exhibit mutagenic activity for test strains S. typhimurium his- TA97a, TA98, TA100 and TA102. PMID- 1297033 TI - [Occurrence of species from Acinetobacter genus in clinical material and other sources]. AB - The analysis regarded 304 strains of Acinetobacter genus isolated from various diagnostic materials, objects from hospital environment and from non-hospital sources (soil, water, various animals). Applying API ZONE system, five species were isolated: Acinetobacter juni, (18.42%), Acinetobacter baumanii (70.39%), Acinetobacter haemolyticus (5.59%), Acinetobacter lwoffii (4.6%) and Acinetobacter johnsonii (0.99%). Most frequently isolated species were present in purulent materials and in samples from respiratory tract infections and urinary tract infections. Over 47% Acinetobacter species strains were present in clinical material as single aerobic bacteria. PMID- 1297034 TI - [Occurrence of Clostridium difficile in the digestive system of dogs]. AB - This study was aimed at seeking strains of Clostridium difficile in feces and investigation of influence of antibiotics application on frequency of isolation and detection of toxing in vivo produced by this microorganism. Samples of feces were obtained from experimental dogs consisting of two groups. To groups I belonged 150 healthy dogs. Group II consisted of samples of feces received from four dogs before and after application of various antibiotics. Clostridium difficile was not isolated from group I dogs. From dogs belonging to group II, 28 strains were isolated. Production of toxing and classification to serological groups of the isolated strains were performed. Presence of this microorganism in feces of dogs is evident only after multiple application of antibiotics. Results of these studies suggest that dogs may constitute a reservoir of Clostridium difficile. PMID- 1297035 TI - [Problems encountered in identification of penicillin binding proteins with pneumococcus used as an example]. AB - Whole cells or isolated membranes of Streptococcus pneumoniae were treated with labelled benzyl penicillin and the penicillin binding proteins (PBPs) were visualized by fluorography after SDS-PAGE electrophoresis. The PBP profiles obtained for strains sensitive and resistant to penicillin strongly differed depending not only on the concentrations of acrylamide and bis-acrylamide used in the separating gel but also on the batch used (different manufacturers). The latter was also true for sodium dodecyl sulfate. PMID- 1297036 TI - [Rapid preliminary diagnosis of anaerobic bacterial infections. I. Natural fluorescence of pus, purulent fluids and dressing under UV radiation]. AB - For evaluation of usefulness of natural fluorescence of clinical materials in UV radiation as rapid diagnostic method of infections with anaerobes, 405 samples of pus, bloody-purulent fluids, blood, wound secretions, dressings and other materials were investigated. Occurrence of red-brick UV fluorescence of clinical materials was compared with results of culture aimed at isolation of non sporeforming anaerobes from "B. melaninogenicus group (P. melaninogenica, P. intermedia and P. saccharolytics). Significant correlation red-brick fluorescence of clinical materials resulting from UV irradiation with presence in these materials of anaerobes such as P. melaninogenica, P. intermedia and P. asaccharolytics was detected. Investigation of clinical materials with application of fluorescence in UV radiation lasts only 1-2 minutes and together with preparation and microscopical inspection which is Gram-stained--only 15-20 min. Positive results of this test may constitute a basis for rapid, preliminary identification of the etiologic factor and for direction of chemotherapy in the early period of infection. PMID- 1297037 TI - [Rapid preliminary diagnosis of anaerobic bacterial infections. II. Investigation of the presence of volatile and non-volatile fatty acids (C1-C6) in pus, purulent fluids and dressing by application of gas chromatography]. AB - Studies were performed in the years 1986-1990 and dealing with 405 clinical materials originating from infections within the abdominal cavity, maxilla, reproductive organ, post-operative wounds as well as dressings, extremities, blood, bile and other types of material and usefulness of analysis by gas chromatography of presence of lower fatty acids in materials for rapid and preliminary diagnostics with strictly anaerobic bacteria was confirmed. Presence in chromatograms of isobutyric, butyric isovaleric, valeric, isocaproic and caproic acid, and partly of propionic acid, is a good indication of infection with strictly anaerobic bacteria. Moreover, presence of succinic acid may suggest presence of anaerobic infection, similarly as presence in chromatograms of three or more various lower fatty acids. Rapid, approximative diagnosis of anaerobic bacteria by application of gas chromatography is worth of broader application. Investigation of clinical material by this method lasts only 1-2 hours and obtained results my present a basis for preliminary diagnosis of the etiological factor and for direction of chemotherapy, which is very important in most early period of treatment of infections. PMID- 1297038 TI - [Adherence in vitro of Candida albicans to cheek mucous membrane cells in children with immune disorders]. AB - Evaluation regarded adherence of a strain of Candida albicans to epithelium of cheek mucous membrane, obtained from 31 children aged between one and 14 years with disturbance of immunity and from 10 healthy children. All children were tested immunologically by determination of total leukocytosis, granulocytosis, absolute lymphocytosis, active and total rosette tests, spontaneous and stimulated nitroblue-tetrazolium (NBT) tests and immunoglobulin A, G and M levels in serum. Adherence of C. albicans in vitro of epithelial cells of cheek mucous membrane was significantly higher in children with disturbance of immunity as compared with healthy control group (p < 0.001). PMID- 1297039 TI - [Candida krusei in genital infections]. AB - Frequency of appearance of Candida krusei in human reproductive tract, susceptibility of these microorganisms to drugs and their importance in pathogenesis of mycosis, were investigated. Strains C. krusei species constituted 6.7% of the total 1325 strains and 21.8% within other than C. albicans species yeast-like fungi. Vaginal mycosis caused by fungi from C. krusei species occurs in presence of Lactobacillus sp. and correct values of pH in vaginal contents, however changed leukocytosis in evident. Over 60% of patients with C. krusei infection were complaining that they feel disturbances within the reproductive tract. Investigation of susceptibility of C. krusei to drugs revealed highest activity of cotrimazine and pimaricin. PMID- 1297040 TI - [The role of Candida kefyr (C. pseudotropicalis) in reproductive tract infections]. AB - Frequency of appearance of C. kefyr strains, their diagnosis, susceptibility to drugs and importance in pathogenesis of reproductive tract mycoses were investigated. The investigated material consisted of 2717 strains, and there were 67 strains of C. kefyr isolated from vaginal mucous membrane. C. kefyr strains constituted 2.5% of total number of 2717 isolated strains and 8.2% within fungi other than C. albicans species. Vaginal mycosis caused by C. kefyr occurs in presence of Lactobacillus sp. and correct values of pH in vaginal contents, however changing leukocyte number was observed. Clinical symptoms and complaints regarding reproductive tract were present in 47.8% of patients with C. kefyr infections. Investigating susceptibility to antimycotic drugs, regardless of appointed method, low susceptibility of C. kefyr strains to amphotericin B was noted (79% resistant strains). Strain of C. kefyr were sensitive to all remaining drugs. PMID- 1297041 TI - [Age specificity of the interaction of Bacillus cells with a liquid-gas interface]. AB - The age specificity of the bacilli cells with liquid--gas interface was studied using flow cytofluorometry. This interactions is dependent on the position of the cell in the division cycle and not on the position of the cell in the DNA replication cycle. PMID- 1297042 TI - [Dynamics of the interaction between Pseudomonas aeruginosa bacteriophage phimF81 and host bacteria]. AB - The population interactions of Pseudomonas aeruginosa virulent bacteriophage phi mF81 with host bacterial cells were studied in dynamics under the conditions of continuous cultivation in the chemostat regime with glucose limitation. It was detected that a maintenance of the bacterium and its specific bacteriophage in the population was realized due to the successive appearance of bacterial mutants resistant to the phage and of phage mutants overcoming this resistance. PMID- 1297043 TI - [Survival of Escherichia coli cells during storage in suspensions of varying concentrations]. AB - The presence of positive correlative connection between death rate of Escherichia coli M-17 cells and the density of their suspension have been estimated. It has been shown, that the accumulation in extracellular medium (ECM) of death stimulating (DS) metabolites, the concentration of which was higher in the suspensions of higher densities, was the immediate cause of the acceleration of death in suspensions with densities higher than 1 x 10(9) cells/ml. DS metabolites could be removed from ECM by adsorption or dialysis, and, thus, they had comparably low molecular mass. The presence of DS metabolites led to the acceleration of death of test-cultures E. coli M-17. The filtrates of ECM of suspensions with density lower than 1 x 10(9) cells/ml did not accelerate the death rate of test-cultures, and, most probably, did not contain any DS substances. It is supposed, that the role of DS-substances is the maintenance of optimal size of the population of bacteria. The low effective concentrations of these substances make it possible to consider that their functions are nothing but regulatory. PMID- 1297044 TI - [Preservation of Pseudomonas putida bacteria at low temperatures]. AB - We have found that the mode of cooling, composition of cryopreservation medium, original concentration of cells and storage temperature affect viability of Pseudomonas putida bacteria during low-temperature preservation. We have elaborated the conditions of preservation, providing for a high survival of bacteria, namely: one-stage cooling with the rates of 30, 40 degrees C/min or immersion into liquid nitrogen in the culturing medium with addition of sucrose, glycerol or dimexide in the concentration of 0.5 M; storage temperature is -80 degrees C divided by -196 degrees C. PMID- 1297045 TI - [Effect of exogenous ribonucleases on the propagation of Candida tropicalis yeast]. AB - The effect of exogenic microbial and tissue RNAses on the reproduction of Candida tropicalis yeasts were studied. Catalytically active and inactive forms of ribonucleases were shown to stimulate yeast organism reproduction. Using immunochemical and radioisotopic methods, it was found that RNAses penetrated into yeast cell. The correlation between yeast cell penetration by exogenic enzymes and the physiological state of the cells was revealed. The activation of the chromatin associated RNAse-polymerase under the action of the catalytically active binase was observed in in vitro experiments. The mechanisms of the stimulatory effect of catalytically active and inactive RNAses on growth and reproduction of C. tropicalis are discussed. PMID- 1297046 TI - [Penetration of pancreatic DNase into Candida tropicalis cells]. AB - Permeability of Candida tropicalis cells for exogenic DNAse was studied by a cytochemical method. The enzyme were shown to penetrate yeast outer membrane and cell wall after a 20 minute incubation period when incubated together with cells at the beginning of the stationary phase. PMID- 1297047 TI - Polycyclic aromatic hydrocarbon pollution from the aluminium industry. AB - Polycyclic aromatic hydrocarbons, the major air pollutants emitted by two aluminum reduction plants in Hungary, were measured in the emission dusts and in air particulates in nearby residential areas. There was a higher amount of PAHs in the emission dust of the plant operating with vertical stud anodes (plant "A") compared to the plant operating with horizontal stud anodes (plant "B"). PAHs in ambient air in the town, close to plant "A", were similar to the levels in emission dust, indicating a health hazard for the population. This is strengthened by the non-seasonal variation of benzo(a)pyrene content of ambient air in the town. Measurements of PAHs in the vicinity of the plant "B" and in a town 4 km away clearly showed a decrease in the concentration of the hazardous chemicals. Analysis of emission dusts from the power plant, close to plant "B", showed that 100-fold less PAHs are emitted compared with the plant. Although major technological changes cannot be made, improved emission control would be beneficial to the general population in that area. PMID- 1297048 TI - [Occupational risks in the maintenance of pot-lining and anode firing furnaces]. AB - A group of 66 pot-lining and anode furnace maintenance workers was examined, including 44 workers who had been exposed to these occupational hazards for more than one year. No occupational bronchial diseases were observed. Two cases of 1/0 grade silicosis and two cases of initial palmar aponeurosis retraction were reported. Seventeen cases (38.6%) of occupational hearing loss had been compensated or reported. Hearing loss exceeding the 2nd degree of the Merluzzi scale was observed in 11 workers. There were 13 cases of hearing loss (29.5%) according to ISO criteria, due to exposure levels calculated at 95/100 dB-A eq. Spirometry revealed only one worker with marked reduction in vital capacity. Urinary fluoride concentrations (1.37, S.D. = 0.63 pre-shift and 2.32, S.D. = 1.15 post shift) did not indicate any particular level of hazard. ECGs showed no significant alterations. Variance analysis and multiple regression techniques were used to study the relationship between respiratory volume, hearing capacity, age, duration of exposure and length of past exposure in the construction industry. A marked association was observed between age and hearing loss and a weaker association between duration of exposure and hearing loss. PMID- 1297049 TI - Respiratory disorders in aluminium potroom workers. AB - Epidemiological studies of aluminum potroom workers have been in progress in Norway since 1986. The occurrence of work-related asthmatic symptoms and their determinants were studied. Work-related asthmatic symptoms and airflow limitation were closely associated with duration of potroom employment. A significant relationship between current fluoride exposure and work-related asthmatic symptoms was observed in a smaller, cross-sectional population where a detailed exposure classification was carried out. A similar association and also a dose response gradient was found in a longitudinal study of new employees. The existence of occupational asthma in aluminium potroom workers was confirmed by characteristic patterns of repeated peak flow measurements supported by changes in methacholine responsiveness in workers with suspected work-related asthma. Current smoking as a risk factor for work-related asthmatic symptoms was observed both in cross-sectional and in longitudinal investigations. Similarly to current fluoride exposure, a dose-response gradient was demonstrated in the association between work-related asthmatic symptoms and current amount of tobacco smoked. Allergy was not shown to be a determinant of work-related asthmatic symptoms in any part of the investigation. A family history of asthma and previous occupational exposure may have had some influence on the risk of developing symptoms but the findings were inconsistent and probably of minor importance. Methacholine challenge seemed inappropriate for the screening of aluminium potroom workers in order to detect work-related asthmatic symptoms, but was closely correlated to the severity of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297050 TI - Follow-up of airway reactivity in potroom workers in relation to exposure. AB - Two groups of workers were studied: a) 24 workers with respiratory complaints--7 of whom were light and 4 borderline hyper-reactors--who continued to work on the electrolytic reduction of aluminium for up to two years; b) 30 workers with increased bronchial reactivity who ceased to work in potrooms for 3.7 years on average (range 2-11 years) because of respiratory complaints. Subjective respiratory complaints were recorded and a non specific bronchial reactivity test was performed one or two times during the follow-up period. A sustained level of airway reactivity was recorded in both groups of workers regardless of exposure conditions. In workers with dyspnoea and airway obstruction, bronchial reactivity did not worsen in spite of continued exposure. On the other hand cessation of exposure was not followed by normalization of bronchial reactivity. The potential role of atopy, smoking habits and length of previous exposure was analyzed. It appears that increased bronchial reactivity, once induced, has a tendency to persist. An improvement in subjective complaints may be expected after cessation of exposure. PMID- 1297051 TI - Histamine provocation test: an effective pre-employment selection method for aluminium workers. AB - A descriptive study was made at a primary aluminium smelter to find evidence of the efficiency of the Histamine Provocation Test as part of a pre-employment examination. 174 cases of potroom asthma were divided into two groups. 157 cases were employed in the years 1970-1981. The second group consisted of 17 men who were employed after the introduction of the HPT in 1982. The urinary fluoride levels showed a lowering in exposure to fluorides during the last five years. Medical data collected at the pre-employment examination was compared between the two groups. There were significantly more smokers in the first group of 157 men. Bronchitis or asthma during childhood was mentioned by many men in the second group. It is concluded that the HPT played an important role in the attempt to reduce the incidence of potroom asthma, followed by greater attention to working conditions. PMID- 1297052 TI - [Potroom asthma: irritative bronchospasm or due to sensitization?]. AB - The incidence of occupational bronchial asthma (potroom asthma) among workers employed on electrolytic reduction of aluminium is between 0.4 and 4%. No precise etiological agent has been identified; irritating agents are usually blamed, especially fluoridric acid, dusts, and SO2. Nevertheless, some features of potroom asthma, such as the moderate prevalence, the latency period, the progressive increase in sensitivity with continuing exposure, the appearance of symptoms several hours after the beginning of the work shift, the persistence of symptoms and of aspecific bronchial hyperreactivity even after withdrawal from the working environment, suggest the possibility of occupational asthma due to sensitization. Knowledge of the pathogenetic mechanism has direct influence on prevention: in the case of asthma due to irritants it may be sufficient to comply with the TLV, while in the case of sensitization, even low levels of exposure can be sufficient to trigger off the symptoms of bronchial asthma. PMID- 1297053 TI - Eosinophil-related respiratory disease in aluminium workers. AB - We carried out a nested case-control study in an aluminium producing plant, using the results of pre-employment examination to identify workers with an increased risk of developing work-related obstructive respiratory symptoms. Cases (n=49) are those who had become unable to work because of work-related respiratory disease. They were compared with 49 matched controls. Pre-employment eosinophil count was strongly related to the occurrence of work-related obstructive respiratory disease. This finding is interesting in the light of a possible pathogenesis. PMID- 1297054 TI - [Respiratory symptoms and pulmonary function in the Italian primary aluminum industry]. AB - The paper reports the results of a longitudinal study of 1478 workers in the primary aluminium industry in Italy (aluminium reduction with the pre-baked anode process) covering the prevalence and incidence of chronic obstructive lung disease, chronic bronchitis and bronchial asthma, and analysis of lung function deterioration over time (annual decline in FEV1) in relation to occupational exposure and individual non-occupational features. The incidence of respiratory symptoms of chronic cough and expectoration was significantly higher among electrolytic shop workers, in whom the annual decline in FEV1 was also significantly greater. In this group the incidence and prevalence of asthmatic manifestations was particularly high compared to casting and workshop workers. Asthmatic symptoms showed a short latency period related to exposure in potrooms and seems to be characterized by a marked deterioration in lung function over time even after withdrawal from exposure. PMID- 1297055 TI - [Chronic bronchitis and respiratory function in those employed in primary aluminum production]. AB - A study was carried out on a group of 323 workers of a primary aluminium production plant located in Porto Marghera (Italy) in order to assess the prevalence of chronic bronchitis and respiratory function alterations, compared with the general working population of the same industrial area. The results showed a higher prevalence of chronic bronchitis (5.6% compared with 2.6%) and a greater reduction in vital capacity but only in the non-smokers (5.4% compared with 1.7%). The highest prevalence of chronic bronchitis (20%) and reduced vital capacity (27%) was observed in the rodding section. The frequency of bronchial obstruction was similar to that observed in potroom and casting workers. PMID- 1297056 TI - [A retrospective assessment of 19 subjects compensated for the inhalation of aluminum powders (item 48, D.P.R. 482/75)]. AB - A study was made of 19 male subjects, mean age 54.7, S.D. 7.5 years, exposed to risk of aluminium dust inhalation for 16, S.D. 9.7 years, awarded compensation by the local provincial branch of INAIL (National Institute for Insurance against Occupational Accidents) in the period 1975-1988, as prescribed by item 48 of Presidential Decree 482/1975. The workers were divided into two groups on the basis of radiological signs of lung fibrosis (3 1/1 cases and 7 1/0 cases according to the ILO classification) or of COPD (Chronic Obstructive Pulmonary Disease) (9 cases). Careful examination of the work histories confirmed the previous observations of aluminium pneumoconiosis with moderate functional alterations in alumina production, potroom and casting workers. PMID- 1297057 TI - [The laryngeal status of the workers of 2 plants producing primary aluminum]. AB - The paper reports the results of an indirect laryngoscopic investigation performed in the two-year period 1988-89 on 347 workers in two different primary aluminium production plants. A model is proposed for classification of the laryngeal state into 4 classes of increasing severity of clinical findings. An analysis was made of the statistical relationship between laryngeal class, occupational exposure, cigarette smoking, alcohol consumption, and age. A multivariate analysis of the data was performed using the logistic regression test. Smoking and age were shown to have a statistically significant influence (p < 0.0001 and p < 0.005 respectively) on the development of chronic laryngitis. No statistically significant difference was observed for alcohol consumption and in the comparison between workers and controls. PMID- 1297058 TI - [The occupational risks in a company producing aluminum alloy wheels]. AB - An environmental hygiene study was carried out in a factory making aluminium alloy wheels via pressure moulding. Physical risk factors (noise and microclimate) and chemical risk factors (respirable dust, mineral oils, solvents, fluorides, formaldehyde, CO) were assessed. Analysis of the data showed that physical risk factors were prevalent, whereas chemical pollution was insignificant due to technical improvements made by the management in the course of several redesigns of the plants. PMID- 1297059 TI - Longitudinal study of workers of an aluminium die casting factory. AB - We conducted a 5-year longitudinal study on 76 workers of a high and medium aluminium alloy die-casting factory. As in a previous cross-sectional study conducted in 1986 and in accordance with the data in the literature, the 1990 follow-up study showed: a low prevalence of chronic bronchitis (as defined by the ECSC questionnaire on respiratory symptoms); normal mean functional values of FVC, FEV1, FEV1/FVC%. We did not find any significant difference in the levels of lung function over the period of 1986-90. These results show that workers in the secondary aluminium industry are not exposed to a significant risk of chronic pulmonary disease. PMID- 1297061 TI - [Biological monitoring of occupational exposure to aluminum]. AB - The meaning and usefulness of biological indicators in the study of occupational exposure to aluminium (Al) was assessed on the basis of the most recently acquired knowledge on the toxicokinetics of aluminium absorbed by inhalation, results of environmental and biological investigations recently carried out in industrial sectors with low risk of aluminium absorption (refining, casting and pressure moulding covering a total of 8 plants and 119 workers) and the results of investigations on a group of welders exposed to Al concentrations between 5 and 10 mg/m3. It was confirmed that not only the environmental Al concentrations but also certain chemical and physical characteristics (particle size, allotropic state, solubility), simultaneous exposure to other dusts, and mode of exposure (existence of exposure peaks) play a significant role in lung absorption of Al. Urinary Al (AlU) may be considered as an indicator of "recent" exposure with biphase excretion kinetics influenced also by duration of exposure, whereas Al in serum (AlS) can probably furnish indications both on overall exposure and on body burden. In low-level Al exposure (below 0.5 mg/m3), these indicators (especially AlU) permit differentiation of the exposed groups from the general population without, however, any clear relationship with the various environmental Al concentrations. It was also seen that AlU increased with increasing work seniority and was more marked in certain processes, such as casting, and in the first few months or years of work.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297060 TI - Biomedical aspects of aluminium. AB - About 2.5 mg of aluminium is absorbed daily with food; it then undergoes minimal absorption via the gastrointestinal tract (0.1%) and total excretion of the absorbed dose via the kidneys. The concentrations of aluminium in blood of non exposed subjects with normal renal function are extremely low (1-3 micrograms/L). Until the beginning of the 1970's aluminium was considered to be of little toxicological interest, but in 1972 a neurological syndrome due to aluminium intoxication was described in dialysis patients in the UK and in 1973 Canadian research workers speculated on the role of aluminium in Alzheimer's disease (senile or presenile dementia), even though this does not at present have wide support. Al intoxication in dialysis patients can be prevented if the Al concentration in the dialysis solution is kept below 10 micrograms/L. No cases have been reported of systemic intoxication due to aluminium in occupationally exposed subjects. Al in plasma values of 5-15 micrograms/L have been reported in exposed workers, which are 10 times lower than the values observed in dialysis patients with encephalopathic symptoms. However, rare cases of occupational pulmonary fibrosis have been reported where an etiopathological role of aluminium was suspected. Nevertheless, it has been demonstrated that the alumina used in primary aluminium production lacks any fibrogenic potential. PMID- 1297062 TI - Proposal of a dose-response relationship between aluminium welding fume exposure and effect on the central nervous system. AB - Exposure to high levels of aluminium can affect the human central nervous system. Abnormalities of psychomotor function have been observed among haemodialysis patients with mean aluminium concentrations in serum of about 60 micrograms/l. According to our own data this corresponds to a urinary level of about 330 micrograms Al/l in aluminium-exposed welders without kidney failure. This post shift urinary level of aluminium is estimated to be attained after 40 years of exposure to a welding fumes at an environmental concentration of approximately 1.6 mg/m3 of aluminium. An increased prevalence of effects on the nervous system was observed among welders exposed to aluminium fumes for more than 13 years. This finding supports the concept of cumulative toxicity due to aluminium exposure. On the basis of these observation, we suggest that the level of aluminium in welding fumes should not exceed 1 mg/m3. PMID- 1297063 TI - Evaluation of fluoride exposure in aluminium smelters: state of the art. AB - Measurements for assessment of exposure to fluoride in aluminium smelters were generally introduced about 15 years ago. A good correlation between fluoride levels in the urine and the concentration in the ambient air was found. The results of biological monitoring can be used to avoid the risk of the chronic effects of bone fluorosis. Mean values of numerous individual measurements give only the general situation in the plant concerned. For the identification of individuals with high exposure, the individual values must be considered. The urinary fluoride concentration is highly dependent on the urine rate. To obtain a measurement either from a long-term body burden or a short-term exposure the daily eliminations before work (pre-shift value) or immediately after a shift (post-shift value) must be known. Since the collection of 24-hour urine samples not feasible, it is necessary to correlate the fluoride elimination to the daily creatinine excretion, which amounts on the average to 1.8 g. The role of the HF regarding acute irritation of the respiratory tract is not yet fully clear. More information must be obtained by measuring peak values of short periods of time which are expected to be much higher and also more effective than the average values measured over a whole shift period. The suitable instruments for determination of peak values of HF are not yet available. PMID- 1297064 TI - [The prevention of tumors in the aluminum industry]. AB - Aluminium industry workers are exposed to various carcinogenic substances, the most important of which are asbestos and coal pitch and tar fumes. Primary prevention of cancer risk can be achieved either by eliminating the carcinogenic agent from the working environment, or by reducing the exposure levels or the number of exposed workers. In the aluminium industry the first type of approach is possible in the case of asbestos, which can be substituted with MMMF (man made mineral fibers), with the cancer risk thus passing from group 1 to group 2b of the IARC Classification. Complete abolition of exposure to pitch and coal-tar fumes is not feasible, but a reduction in risk can be achieved by using the pre bake anode cell process instead of the Soderberg process, since the former reduces exposure of potroom workers to pitch and coal-tar fumes. A further reduction of exposure in pot-rooms can be achieved, as demonstrated by direct experience in an aluminium plant at Port Marghera (Province of Venice). Environmental monitoring performed from 1978 to 1989 showed a decrease in levels of total dust concentrations and thus of PAH and BaP concentrations as a result of a series of technical and/or organisational improvements. In biological monitoring, which can detect any skin absorption of the carcinogen, the concentrations of urinary hydroxypyrene confirmed low levels of exposure in the plant under study, excluding the pitch plant workers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297065 TI - Biomonitoring of genotoxic exposure of aluminium plant workers. AB - Humans are environmentally and occupationally exposed to polycyclic aromatic hydrocarbons (PAH). PAH's are a class of tumorigenic compounds which act through metabolic transformation to chemically reactive forms, epoxides, which covalently bind to DNA forming DNA adducts. To evaluate the genotoxic effects of PAH's, air and urine samples were analyzed for PAH. Blood samples were analyzed for benzo(a)pyrene-diol-epoxide-DNA (BPDE-DNA) adducts. New methods for analyzing DNA adducts in lymphocytes have been used to study the genotoxic effects of human exposure to carcinogens. BPDE-DNA adducts in lymphocytes have been used as internal dosimeters of exposure to PAH's and several studies have been conducted. We measured BPDE-DNA adducts in aluminium plant workers with immuno-assay and physico-chemical methods. PAH-DNA adducts were detectable to a lesser extent in subjects working in an aluminium plant compared to subjects working in a coke oven plant. PMID- 1297066 TI - [The urinary mutagenicity test in monitoring exposure to aromatic polycyclic hydrocarbons in workers in the aluminum industry]. AB - The sensitivity of 3 urinary mutagenicity tests was assayed: the plate test, the fluctuation test and the micropreincubation test, in order to assess their possible use in monitoring human exposure to polycyclic aromatic hydrocarbons (PAH). Urine samples from workers of an anode production plant exposed to coal tar and from psoriatic patients undergoing treatment with coal-tar ointments were tested for mutagenic activity on strain TA98 Salmonella typhimurium, in the presence of the microsome fraction and deconjugating enzymes. Parallelly, the urinary concentration of PAH metabolites or one of their trace metabolites, 1 hydroxypyrene, was determined. Increased levels of PAH metabolites were observed in the urine of anode production workers after a work shift compared with controls. Results of the plate test and the fluctuation test performed on urine of exposed subjects, both smokers and nonsmokers, showed mutagenicity values similar to the controls. Much higher 1-hydroxypyrene concentrations were found in the urine of psoriatic patients treated with coal tar than in post-shift urine of anode production workers. The urine of the former was also mutagenic in the 3 mutagenicity tests used. The minimum mean dose of PAH metabolites was calculated, expressed as quantity of 1-hydroxypyrene, that would give a mutagenic response in the 3 tests: the micropreincubation test was found to be about 100 times more sensitive than the plate test and about 30 times more sensitive than the fluctuation test. The theoretical minimum urinary concentration of 1 hydroxypyrene detectable by each test was determined: the micropreincubation test was 15 times more sensitive than the plate test and 7 times more sensitive than the fluctuation test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297067 TI - Dermal exposure to polycyclic aromatic hydrocarbons among primary aluminium workers. AB - Large amounts of PAH's are released in the electrode production departments of pre-bake cell aluminium reduction plants. Emission sources are mixing, shaping and baking of the anode (paste plant and bake oven) and pot relining operations. A study was performed to quantify the importance of dermal uptake of PAH's among exposed workers. Twenty workers in the anode production departments (paste plant (N = 8) and bake oven (N = 5)) and the pot relining department (N = 7) volunteered for the study. Monitoring was performed over a period of 5 consecutive days using personal air sampling, dermal contamination sampling and biological monitoring. Pyrene concentrations measured in the respirable air samples, ranged up to 320 micrograms/m3. Dermal contamination of pyrene was monitored at three skin sites (wrist, jaw/neck and groin) using exposure pads as pseudo-skin. The skin contamination with pyrene ranged up to 375 ng/cm2. Contamination of the groin skin site, although covered by work clothes ranged up to 106 ng/cm2. The concentration of 1-hydroxypyrene in pre and post-shift urine ranged up to 27 mumol/mol creatinine and showed an increase during the day and a decrease during the night. Pyrene in air and pyrene on the skin were tested for significance of correlation with urinary 1-hydroxypyrene in samples taken at several moments: end-of-shift, pre-shift next morning and weekly increase. The correlation coefficients between dermal contamination and urinary 1-hydroxypyrene were equal or higher than the correlation coefficient between pyrene air concentration and urinary 1-hydroxypyrene. The total skin contamination in exposed workers is estimated to be more than three times higher than the intake via the respiratory tract. The contribution of dermal exposure to the total PAH body burden of exposed workers therefore appears to be significant. PMID- 1297069 TI - Close association of peptidergic nerves with lymphocytes in canine and monkey ileal villi. AB - Intimate association of peptidergic nerves with lymphocytes of canine and monkey ileal villi was demonstrated by immunohistochemistry and transmission electron microscopy. A swollen, presumably terminal, portion of nerves containing large cored vesicles and small clear vesicles was in direct contact with a lymphocyte. The apposing membranes of the nerve and lymphocyte were thickened and darkened, being separated by a narrow uniform space. The lymphocyte-associated nerves contained immunoreactivity for substance P(SP), calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP), localized in large-cored vessels. These result support the hypothesis that peptidergic nerves may play a regulatory role in mucosal immune responses. PMID- 1297068 TI - [Mortality in workers of a primary aluminum foundry in Portovesme in Sardinia]. AB - The standard mortality rates (SMRs) were calculated for 1148 workers of a primary aluminium plant in Portovesme, Sardinia, hired between 1971, when production started, and 1980. Status (living or decreased) was ascertained as at 31 December 1990 and the relationship between observed and expected deaths with respective 95% confidence limits were calculated on the basis of age-specific regional rates for each calendar year of the follow-up. The SMR for all causes was 81 with confidence limits between 61 and 108 based on a total of 48 deaths. Mortality due to malignant neoplasms did not differ from the expected rate. The observed deaths due to lung cancer were decidedly less than the expected number (3 observed versus 4.7 expected). A significant excess of cancer of the pancreas was observed with special reference to anode production, based, however, on only 3 observed cases against 0.8 expected. In the absence of a more precise definition of the causes of death, of the environmental exposure levels and of the non-occupational confounding factors, and considering the young age of the cohort under study, it is at present doubtful whether the excess of cancer of the pancreas can be associated with work in the primary aluminium industry. The results should therefore be taken as preliminary, indicating that further studies are required. PMID- 1297070 TI - A three-dimensional observation of acid phosphatase-positive structures in rat testis by high voltage electron microscopy. AB - Using a fixative of low concentrated glutaraldehyde in PIPES, we examined three dimensional structures of acid phosphatase (ACPase) activity in the cells of testes of normal adult and 30 min heat-treated rats by high voltage electron microscopy. There were less ACPase-positive structures in germ cells, but more in Sertoli cells, particularly in residual bodies, and also in macrophages lying between seminiferous tubules. Reaction products of ACPase were distributed in the trans-most cisternae of Golgi apparatus, many spherical lysosomes, and acrosomes. The elongated thread-like lysosomes (nematolysosomes) were absent on the testicular cells. After heat-treatment of rat testis, though ACPase-positive lysosomes increased in number, nematolysosomes were never seen in Sertoli cells and most of the other testicular cells; a number of rod-like lysosomes, however, emerged in macrophages. The results indicate that (1) Sertoli cells usually have more ACPase-positive lysosomal contents than germ cells; (2) Sertoli cells are less affected by stress which may largely hurt germ cells; (3) nematolysosome is not a ubiquitous structure in all the types of cells; and (4) the function of nematolysosomes in macrophages may involve in the disposition of disintegrated cells in rat testis. PMID- 1297071 TI - Ultracytochemistry of glucose-6-phosphate dehydrogenase in adrenal gland. AB - The distribution of glucose-6-phosphate dehydrogenase (G6PD) activity has been studied by a copper ferrocyanide method in the adrenal cortex cells of a rat. The site of the G6PDH activity was close to the ribosome between the round mitochondria of zonas fasciculata and reticularis. PMID- 1297072 TI - Nursing Times open learning programme. R3: research approaches. Part (ii): The view from above: experiments and surveys (continuing education credit). PMID- 1297073 TI - Caring for the community. PMID- 1297074 TI - Acute problems. PMID- 1297075 TI - A breach of trust? PMID- 1297076 TI - Hype and prejudice? PMID- 1297077 TI - The named nurse. Let's name names. PMID- 1297078 TI - The named nurse. A question of accountability. PMID- 1297080 TI - Ward sisters. Budget day. PMID- 1297079 TI - A new lease on life. PMID- 1297081 TI - Systems of life. Joints. I. PMID- 1297083 TI - Infection hazards of patient lifting slings. PMID- 1297082 TI - Comparing treatments for menorrhagia. PMID- 1297084 TI - Scoring dependency in critical care. PMID- 1297085 TI - Time to grow up. PMID- 1297086 TI - The other lady with the lamp. PMID- 1297087 TI - Practice nursing. Practice makes perfect. PMID- 1297089 TI - Kaposi risk from faecal contact. PMID- 1297088 TI - Practice nursing. Thirst for knowledge. PMID- 1297090 TI - Election poll. Labour's health lead. PMID- 1297091 TI - Midwifery renaissance. PMID- 1297092 TI - Professional priorities. PMID- 1297094 TI - Getting it down on paper. PMID- 1297093 TI - Body politic. Not so simple. PMID- 1297096 TI - Patchy vision. PMID- 1297095 TI - Stress. Understanding support. PMID- 1297097 TI - Programme for progress. PMID- 1297098 TI - The rough guide to change. PMID- 1297099 TI - Hospital and nursing home care for the elderly in an inner city health district. AB - This study reports process data on everyday life in an NHS hospital and two nursing homes for elderly people. The interviews revealed low expectations of respondents, although observational data confirmed the superior quality of life in the nursing homes. The responses of the elderly people, however, do illustrate the types of activity they would like to engage in to improve their quality of life. PMID- 1297100 TI - Midwifery. The direct route. Interview by Philippa Cardale. PMID- 1297101 TI - Continence. A basis for change. PMID- 1297102 TI - Continence. Undercover trials. PMID- 1297103 TI - Continence. Catheter tips. PMID- 1297104 TI - Continence. Part of the problem. PMID- 1297105 TI - Continence. Hard won comfort. PMID- 1297106 TI - Continence. Providing an informed service. PMID- 1297107 TI - A comparison of antihypertensive properties of captopril and enalapril after single and multiple oral administration in spontaneously hypertensive rats. AB - Oral dose of enalapril or captopril moderately reduced the blood pressure of the spontaneously hypertensive rats (SHR) but not those of normotensive rats. The single daily dose of captopril (30 mg/kg) produced antihypertensive response equivalent to enalapril (3 mg/kg). Chronic administration of these drugs for 2 weeks revealed that systolic blood pressure was reduced more by captopril than enalapril. We did not find differences in hypotensive activity between Enalapril IF and Renitec Merck as well as Captopril JZF Polfa and Capoten Squibb. PMID- 1297108 TI - Influence of ethanol on the antiarrhythmic activity of verapamil. AB - The aim of this work was to determine the influence of ethanol on the antiarrhythmic activity of verapamil in the model of calcium arrhythmia in rats non-dependent and dependent on ethanol. The results of the experiment show that a combined, single administration of ethanol and verapamil attenuates in a statistically significant manner the antiarrhythmic effect of verapamil. Ethanol administered repeatedly together with verapamil does not diminish the antiarrhythmic activity of verapamil. PMID- 1297110 TI - Influence of nifedipine on aortal cholesterol content, blood coagulation and elastin metabolism in cholesterol-fed rabbits. AB - Our studies showed that the nifedipine in daily doses of 30 mg/kg given to rabbits treated with a diet containing 1% cholesterol for 6 months, decreased cholesterol content in aorta homogenates, urine excretion of desmosines and prolonged partial thromboplastin time, while it did not alter serum lipids. These results may have some value for understanding of the antiatherogenic mechanism of nifedipine. PMID- 1297109 TI - Interaction between ethanol and diltiazem in the model of barium arrhythmia in the rat. AB - The antiarrhythmic action of diltiazem in the model of barium arrhythmia was studied in rats non-dependent and dependent on ethanol. The results of our studies showed that single intragastric administration of ethanol jointly with diltiazem did not significantly attenuate the antiarrhythmic effect of diltiazem. Ethanol administered repeatedly and jointly with diltiazem influenced the antiarrhythmic action of diltiazem in different ways, depending on the used dose of diltiazem. After repeated joint administration of ethanol and diltiazem in a lower dose, attenuation of the antiarrhythmic effect of diltiazem was not observed. Repeated joint administration of ethanol and diltiazem in a higher dose attenuated the antiarrhythmic effect of diltiazem. Those experiments also showed that single administration of diltiazem did not significantly influence the ethanol level in the blood; however, when administered repeatedly, diltiazem reduced the concentration of ethanol in blood. PMID- 1297111 TI - Pharmacokinetics of amikacin in gamma-irradiated mice. AB - Concentrations of amikacin in sera, investigated 24 h after irradiation with 9 Gy gamma-rays of mice, were monitored using TDX system (Abbott), based on the fluorescence polarization immunoassay. Pharmacokinetic parameters of disposition (distribution + elimination) of the drug were calculated from the obtained data. In irradiated mice fast and slow phases of amikacin disposition were noted. In contrary, in the non irradiated mice only one-fast phase of the drug disposition was observed. The dependence of the disposition parameters of the antibiotic to the postirradiation tubular dystrophia and vascular changes was discussed. PMID- 1297112 TI - Synthesis and central pharmacological screening of new aminoalkoxy derivatives of coumarin and chromene. AB - Several 8-(2- and 3-aminoalkoxy) derivatives of coumarin and 5-(2- and 3 aminoalkoxy) derivatives of chromene have been synthesized. The strongest, although short-time neurodepressive activity was exhibited by 8-[3-(4-phenyl-1 piperazinyl)propoxy]-7-methoxycoumarin hydrochloride 15. PMID- 1297113 TI - Synthesis and preliminary pharmacological assessment of novel 9-alkylamino substituted pyrimidino-[2,1-f]-purines. AB - Two series of N9-alkylaminomethyl-, alkylpiperazino-, alkylpiperidino-substituted 1,3-dimethyl-(hexahydropyrimidino)- and (tetrahydropyrimidono)-[2,1-f]-purines were prepared and their physicochemical and pharmacological properties were described. The most active in central nervous system tests were the compounds with phenylpiperazinealkyl substituent i.e. 1,3-dimethyl-2,4-dioxo-9-[N1N4 (phenyl)-piperazinopropyl]-1, 3,6,7,8,9- hexahydropyrimidino-[2,1-f] purine 6a and its butyl and isobutyl homologs 9 and 12. The compounds depressed statistically significantly spontaneous locomotor and amphetamine activity and showed sedative, analgetic and hypothermizing properties. PMID- 1297114 TI - New proctolin analogs modified in position 3 of peptide chain--synthesis and their biological evaluation. AB - Six proctolin analogs modified in position 3 of peptide chain such as Arg-Tyr-X Pro-Thr where X = Gly (1), Val (2), Pro (3), Thr (4), Acp (1-aminocyclopentane-1 carboxylic acid residue) (5), and Ach (1-aminocyclohexane-1-carboxylic acid residue) (6) were synthesized by liquid-phase method. Biological effects of the pentapeptides (1-6) were examined in cardiostimulatory test in vitro in respect to two insect species: American cockroach (Periplaneta americana L.) and yellow mealworm (Tenebrio molitor L.). Results thus obtained pointed out that the presence of L-leucine in the position 3 of proctolin skeleton plays important role in its cardiotropic activity in insects. PMID- 1297115 TI - Structure-activity relationship studies of CNS agents. Part VII. The effect of the imidazole fragment in 2-substituted 1-[3-(4-aryl-1 piperazinyl)propyl]imidazoles on their interaction modes with 5-HT1A and 5-HT2 receptors. AB - The synthesis and the 5-HT1A and 5-HT2 receptor affinity of 2-substituted 1-[3-(4 aryl-1-piperazinyl)propyl]-imidazoles (1-8) has been described. It has been shown that both the N-3 imidazole atom and the N-1 piperazine one should be considered as possible protonation centers under physiological conditions. It has been found that the folded conformations of 1-8 exist predominantly in solution. Moreover, three different modes of interaction of the analyzed compounds with 5-HT1A and 5 HT2 receptor sites have been proposed. PMID- 1297116 TI - Ascorbic acid did not alter the content of conjugated dienes and malondialdehyde in organs of mice. AB - The aim of this study was to explore whether ip administration of ascorbic acid (AA) in a dose of 500 mg/kg, once a day for 3 following days, affected the content of lipid peroxidation products: malondialdehyde (MDA) and conjugated dienes (CD) in organs of mice. Injection of AA caused 2.1-, 1.3- and 1.8-fold increase in the concentration of this vitamin in liver, spleen and lungs, respectively, while the content of MDA and CD in these organs did not differ from values found in animals treated with 0.9% NaCl. It suggests that in our animal model AA did not act as a prooxidant enhancing the lipid peroxidation in various tissues. PMID- 1297117 TI - [Clinical approach to antiphospholipid syndrome: from facts to questions]. PMID- 1297118 TI - [Treatment with rilmenidine 1 mg per day: time-lag to maximum response. A multicenter ambulatory study. Le Groupe Francais d'etude Multicentrique d'Hyperium]. AB - Forty-four placebo-resistant patients (mean age: 59.2 +/- 2.1 years; mean weight: 70.14 +/- 1.95 kg: mean supine diastolic pressure: 101.6 +/- 0.70 mmHg) were treated during 8 weeks (D0-D56) with a single 1 mg tablet of rilmenidine taken every morning. The patients were seen at intervals of 14 days until their diastolic pressure returned to a normal value of 90 mmHg. Once this goal was achieved, they were not seen again until D56. The actuarial survival curve enabled us to evaluate, at a given moment, the cumulative number of normalized patients and the accuracy of this evaluation (confidence interval). After two weeks of rilmenidine treatment, 66 percent of the patients were normalized. The cumulative proportion of normalized patients increased with time, from 80 percent at D28 to 85 percent at D42 and 98 percent at D56. Confidence intervals were relatively small. Although these results were much better than those obtained in previous studies of this drug, our study shows that blood pressure was rapidly normalized in the majority of hypertensive patients by a daily 1 mg dose of rilmenidine and that doubling this dosage after two weeks of treatment is not necessarily justified, since the percentage of normalized patients increases up to 98 percent after eight weeks of treatment. The small number of adverse effects and the good patient's compliance with treatment (evaluated by tablet counts and rilmenidine plasma level values) testify that this drug respects the quality of life. PMID- 1297119 TI - [Idiopathic hydrocele in adults. Cure by vaginal fenestration]. AB - Among the treatments of idiopathic hydrocele cutting a window in the tunica vaginalis testis stands out as the choice treatment, the procedure being simple and the results of good quality. In the first stage, the two layers, visceral and parietal, of the tunica are folded separately to form the edges of the window. In the second stage the parietal layer of the window is attached to the dartos which remains united with the underlying subcutaneous layer, forming an excellent tract for lymph drainage. Thus, the anatomical and physiological objectives of the operation are reached: the testicular "cockpit" and the protective function of the tunica vaginalis are preserved. In a series of 83 patients operated upon and followed up for up to 5 years, 9 out of 10 were cured by this method without unwanted sequelae. PMID- 1297120 TI - [Glycemic index of foods]. AB - The glycaemic index of foods describes the hyperglycaemic effect of isolated foods. It is measured by the ratio of the area under the glycaemic curve observed after ingestion of a 50 gram carbohydrate dose of the tested food to the area observed after ingestion of the same amount of a reference food (white bread). The glycaemic index classification provides an approach of the diabetic diet based on the glucose response to foods. Widely accepted when applied to isolated foods, its clinical utility during mixed meals remains discussed. The improvement of the average metabolic control which can be expected from its use is modest. However, its major interest could be observed during snacks and meals in order to control precisely post-prandial glucose variations, in association with blood glucose self-monitoring. As it allows high sweet taste-low-glycaemic index carbohydrate foods to be consumed, it could significantly improve the quality of life of diabetic patients. PMID- 1297121 TI - [Volitional and attitude hyperkinesis of an upper limb. Manifestation of an ischemic accident in the territory of the posterior cerebral artery]. PMID- 1297122 TI - [Hypercalcemia in chronic myeloid leukemia]. PMID- 1297123 TI - [Prevalence of HIV seropositivity in men in consultation for gonococcal urethritis at the STD center of Saint-Louis hospital]. PMID- 1297124 TI - [Histiocytic necrotizing lymphadenitis or Kikuchi's disease. Four cases]. PMID- 1297125 TI - [Malignant multi-secretion insulinoma. A case]. PMID- 1297126 TI - [Coronary embolism in hyperthyroidism]. PMID- 1297127 TI - [Respiratory inflammation. Mast cell-macrophage cooperation]. PMID- 1297128 TI - [Non-discal sciatica secondary to a cystic lesion of the posterior longitudinal ligament. 10 cases]. AB - Cyst of the longitudinal posterior ligament of the spine is a new entity described here on the basis of 10 cases. This is a lesion, perhaps of traumatic origin, which occurs in young, athletic subjects suffering from classical lumbosciatica. Computerized tomography showed an image resembling nucleus pulposus herniation. In one of our cases magnetic resonance imaging provided the preoperative diagnosis. Following surgery the outcome was favourable, with less postoperative complications than with discal herniation. The macroscopic and histological findings were the same in all cases, making the anatomico pathological diagnosis easy. PMID- 1297129 TI - [Association of stomach ulcer and Helicobacter pylori. Prognostic implications]. AB - Helicobacter pylori is known to be responsible for most cases of chronic gastritis, but its role in the outcome of gastric ulcer is unknown. The purpose of this study was to determine the prevalence of H. pylori infection before and after treatment of gastric ulcer, the micro-organism being untreated. The trial involved 26 patients with an acute episode of gastric ulcer, who had undergone endoscopy with biopsy of the antrum, the fundus and the ulcer rim at the initial examination and then 6 weeks and 1 year after the diagnosis. At day 0, 25 acute ulcers were associated with chronic H. pylori gastritis; one patient had neither gastritis nor H. pylori infection. The H. pylori count correlated with the activity of chronic gastritis and with the extension of intestinal metaplasia; it was not modified by the healing of gastric ulcer observed in 24/26 patients on day 360. These results confirm the existence of a close association between H. pylori, chronic gastritis and gastric ulcer. It also suggests that H. pylori is not directly involved in the healing or recurrence of gastric ulcer. PMID- 1297131 TI - [Hereditary hypertension in Recklinghausen's disease during pregnancy. A family]. AB - We report the case of a pregnant woman who presented with neurofibromatosis and hypertension the latter revealed by abruptio placentae. Severe hereditary hypertension was noted in the family during pregnancies that were sometimes complicated by intrauterine growth retardation, abruptio placentae and intrauterine foetal death. Thus, neurofibromatosis in a pregnant woman has a poor obstetrical outcome when it is associated with a personal or family history of hypertension. Such women must be treated with extreme care and hospitalized at the end of the third trimester. The advisability of prevention with low-dose aspirin during the first trimester is discussed. PMID- 1297130 TI - [Tobacco, drug and narcotic abuse during pregnancy. Evaluation of in utero exposure by analysis of hair of the neonate]. AB - Hair samples were collected at the time of delivery from 63 neonates whose mothers were known to be heroin (9 cases), nicotine (40 cases), benzodiazepines (11 cases), cocaine (2 cases) and amphetamine (1 case) users. In all cases, the corresponding drug was found in neonatal hair from the infants, with concentrations in the range 0.61-3.47 ng/mg (morphine), 0.15-11.80 ng/mg (nicotine), 3.36-17.55 ng/mg (diazepam), 0.78-31.83 ng/mg (oxazepam), 0.71-2.47 ng/mg (benzoylecgonine), and 1.21 ng/mg (amphetamine). A significant correlation (P < 0.001) was established between nicotine concentration in the hair of the neonates, and in the hair of their mother. PMID- 1297132 TI - [Circulatory assistance through cardiomyoplasty and aortomyoplasty. Experience and first clinical results]. AB - The finding that skeletal muscles can be made resistant to fatigue by progressive electrical stimulation has been used as a means of providing circulatory support in cardiac surgery. The first application of this discovery was dynamic cardiomyoplasty, performed for the first time in man in 1985 at the Broussais Hospital, Paris. The latissimus dorsi muscle is transposed into the thorax, then attached around the heart and finally stimulated synchronously with the ventricular systole. So far, more than 200 patients in the whole world (including 57 at the Broussais Hospital) have undergone this operation with results that are increasingly encouraging. In these cases the muscle is used to reinforce or replace the left or right ventricle, but other applications are being studied, such as double cardiomyoplasty (left latissimus dorsi and right pectoralis major muscles), cardiomyoplasty of the right atrium and aortomyoplasty which produces aortic counterpulsation. The development of these techniques underlines the ever growing interest raised by this type of autologous circulatory support. PMID- 1297133 TI - [Mixed pneumopathies caused by Neisseria meningitidis associated with other bacteria]. PMID- 1297134 TI - [Spontaneous hematoma of the liver during pregnancy. A case]. PMID- 1297135 TI - [Prenatal diagnosis in a family affected by amyloid neuropathy]. PMID- 1297136 TI - [Localized epidermal necrolysis after intravenous injection of vinorelbine]. PMID- 1297137 TI - [Rheumatoid purpura type vasculitis induced by quinidine compounds. A case]. PMID- 1297139 TI - [Systemic manifestations of granulomatous mastitis]. PMID- 1297138 TI - [Pneumocystis carinii pneumonia in a kidney transplantation center in the proximity of an AIDS care unit]. PMID- 1297140 TI - Provoking vasodepressor syncope with head-up tilt-table testing. AB - Head-up tilt testing has proven effective in identifying individuals prone to vasodepressor syncope (VDS). VDS refers to the transient loss of consciousness/cerebral anoxia seen with hypotension produced by autonomic imbalance. In this case, the hypotension is the result of parasympathetic domination. Most episodes appear to be triggered by reduced venous return which stimulates the cardiac mechanoreceptors in the inferior-posterior left ventricle. Once activated, these receptors send out afferent signals along the unmyelinated C of the vagus nerve and cause vasodilation. Once venous return is restored, the usual sympathetic compensations (increased heart rate/force of contraction and vasoconstriction) overcome the parasympathetic domination. A tilt-study allows one to passively tilt the patient up to 40-80 degrees and abruptly reduce venous return in a controlled environment. One can then determine which mechanism will dominate--the usual sympathetic vasoconstriction or the parasympathetic reflex (Bezold-Jarisch)--by frequent observations of blood pressure and ECG. Bradycardia/ventricular standstill may also occur during parasympathetic domination. Once susceptibility to vasodepressor syncope is identified by a tilt study, medications to expand the blood volume and/or minimize venous pooling are often needed. Other drugs to block the parasympathetic pathway and/or the effects of excessive catecholamine levels may also be ordered. Dual chamber pacing may be required for malignant episodes of bradycardia or ventricular standstill. PMID- 1297141 TI - Pregnancy after heart transplantation. AB - The desire to procreate is normal in women, including those who are heart transplant recipients. The female transplant recipient attempting successful conception, pregnancy, and delivery presents a rare challenge to those responsible for her care. This article presents a comprehensive review of pregnancy after heart transplantation in female recipients by reviewing relevant literature, describing the effects of immunosuppressive therapy on reproduction, and suggesting strategies for reproduction counseling. PMID- 1297142 TI - Experiences of patients and significant others with automatic implantable cardioverter defibrillators after discharge from the hospital. AB - Sudden cardiac death (SCD) is a leading cause of mortality in this country. The automatic implantable cardioverter defibrillator (AICD) is a technology which has proven successful in reducing the risk of SCD in patients who qualify for it. However, little is known about how individuals adjust to living with the device. This field study used a focus group technique to investigate the question "What are the experiences of patients and their significant others (S.O.) in the time since being discharged from the hospital with an AICD?" Fifteen AICD recipients and 14 S.O.s each attended one of three focus groups which were tape recorded. Data from the transcriptions were analyzed by a combination of content analysis and ethnographic summary. The major concerns of the patients were [Physiologic], the sensations of being shocked, medications, trouble sleeping, dizziness (accompanied by heat intolerance at times), physical awareness of the device; [Psychosocial], fear, including fear of death and preparation for death, changes in mental functioning, changes in lifestyle including clothing not fitting, loss of control, driving an automobile, and spousal overprotectiveness. The primary psychosocial concerns of the S.O.s were fears, including fear of death and preparation for death, family and role changes, being overprotective and driving an automobile. Mental changes and heat intolerance have not been addressed in the literature previously. PMID- 1297143 TI - Caring for a Marfan patient with cardiovascular complications. AB - The Marfan syndrome is a heritable disorder of connective tissue associated with characteristic abnormalities of the skeletal, ocular and cardiovascular systems. Common cardiovascular manifestations of this syndrome are mitral valve prolapse with mitral regurgitation and dilatation of the ascending aorta resulting in aortic insufficiency, dissection, aneurysm and/or rupture. Although the prognosis for a patient with the Marfan syndrome is significantly more favorable than it was ten years ago, the cardiovascular complications continue to greatly reduce life expectancy. This article presents an overview of the Marfan syndrome including: history and epidemiology, clinical manifestations, diagnostic criteria, surgical intervention and follow-up. A case study is outlined which focuses on priority nursing diagnoses and a plan of care. PMID- 1297144 TI - Regulation of the cerebral circulation by endothelium. AB - Endothelium exerts an important influence on cerebral vascular tone through the production and release of a diverse group of vasoactive factors. Relaxing factors produced by endothelium include nitric oxide (or a nitric oxide-containing compound), a hyperpolarizing factor, and prostacyclin. Endothelium-derived contracting factors include cyclooxygenase products of arachidonic acid and endothelins. Several pathophysiological conditions are associated with increased formation of endothelium-derived contracting factors. Such endothelial dysfunction in the cerebral circulation may shift the balance of vascular tone toward constriction and may potentially contribute to the onset or maintainance of cerebral ischemia and stroke. PMID- 1297145 TI - Rhythms and the pharmacology of lithium. AB - Lithium is the treatment of choice for bipolar affective disorder (manic depression) and is useful in other recurrent affective and nonaffective illnesses. This review discusses lithium's actions on period, phase, amplitude and coupling of biological rhythms that may relate to its therapeutic effectiveness. Alternatively, lithium might interact with environmental light to influence circadian rhythms by an action on the retina. The mechanisms responsible for lithium's chronopharmacological actions are not known, but cellular cations, phosphoinositide or adenylate cyclase second messenger systems, hormones and neurotransmitters may all be involved. PMID- 1297146 TI - Beta A4 amyloid protein and its precursor in Alzheimer's disease. AB - The beta A4 amyloid protein is now understood to play a pivotal role in the development of Alzheimer's disease. This protein is generated by the abnormal processing of the amyloid protein precursor, a large membrane glycoprotein. Insights into the mechanisms of this abnormal processing will give information relevant to the design of new therapeutic strategies for Alzheimer's disease. PMID- 1297147 TI - [Comparative in vitro susceptibility of clinical bacterial isolates to pefloxacin and 14 antibiotics]. AB - In vitro activity of pefloxacin against 782 bacterial strains isolated from hospitalized patients (July-September 1991) in Wroclaw was compared with that of 14 antibiotics (4 aminoglycosides and 10 beta-lactamase). The most susceptible to pefloxacin were: Staphylococcus epidermidis (96.0%), Klebsiella (94.4%), Proteus mirabilis (93.8%) and Escherichia coli (92.7%). The least susceptible proved to be: nonfermentative Gram-negative rods (46.5%), and among them Pseudomonas aeruginosa (19.3% weakly sensitive, 0% sensitive strains). It was found that over 80% of Gram-negative rods were susceptible to pefloxacin, amikacin, netilmicin, cefotaxime and ceftriaxone. The most active against staphylococci were netilmicin (92.6%), pefloxacin (89.4%) and amikacin (82.5%). PMID- 1297148 TI - [Nodular intrabronchial changes in primary tuberculosis of children in the years 1986-1990]. AB - Seventy-seven bronchoscopies have been performed and evaluated in twenty-eight children, aged five months to thirteen years suffering from primary tuberculosis. Endobronchial lesions have been found in 57.1% of the cases. Out of them, broncho nodular fistula was seen in 32.1% of the cases. It has been found out that the frequency of occurrence of this kids of lesions in the actual epidemiological situation is similar that diagnosed several decades ago. PMID- 1297149 TI - [Children cured of neoplasms are seeking their place in society]. PMID- 1297150 TI - [Clinical and therapeutic problems in primary and secondary thrombocythemia]. PMID- 1297151 TI - [Panic disorders and panic-like disorders]. PMID- 1297152 TI - [The course of pregnancy and labor with symptomatic and asymptomatic placenta previa]. PMID- 1297153 TI - [Marian Wictor Leopold Pi,atkowski (1865-1930)]. PMID- 1297154 TI - [Colchicine--mechanism of activity and its utilization in hepatology practice]. PMID- 1297155 TI - [Tricuspid valve prolapse]. PMID- 1297156 TI - [Progress in treatment with insulin. III. Intensive conventional insulin therapy- practical examples of application]. PMID- 1297157 TI - [Progress in insulin therapy. IV. Contemporary principles of insulin therapy in pregnancy with diabetes]. PMID- 1297158 TI - [VIII Annual Meeting of Applied Research on Chagas Disease. Uberaba, 22-24 October 1992. Abstracts]. PMID- 1297159 TI - [Death in the context of obstetric nursing: perspectives of care]. AB - The authors intend to unveil facets of the meaning of mother's care who has lost her baby at the end of pregnancy, in the nursery labor view. For that, they used a Qualitative Research Methodology. The phenomenological methodology of inquiry allowed them to reach the subject of the study. The data were collected from obstetric office employees that answered a guiding question. The analysis of these answers reveals important points linked to this mother's care. PMID- 1297160 TI - [The learning needs of laryngectomized patients]. AB - This study reports the learning needs of laryngectomized patients from a university hospital. The data about how the patients feel about their post surgical condition, were obtained by participant-observation. The patients words were collected in case-studies and related to the learning needs. On the basic of these needs the authors intend to plan the pedagogic action. PMID- 1297161 TI - [Living with an ostomy: a preliminary study]. AB - This study reveals some aspects of ostomy patients life experience. The data were obtained by using the participant observation technique during the monthly meeting session of the Ostomy Patients Association from July 1989 to August 1991. The findings showed that the ostomized patients were concerned with: 1) the ostomy pouch (how to get it); 2) other persons opinion about ostomized patients; 3) their sexuality, and stoma care. The patients perceived themselves as physically disable and inferior persons. Some of them perceived themselves as having a normal life. Other patients also had to cope with the stigma of cancer. PMID- 1297162 TI - [Care: a theoretical review]. AB - This paper focuses on the theoretical review of care and caring in Nursing and other fields, as to meaning, concepts, and perspectives. Care is the essence of Nursing and the author suggests the study and practice of care/caring in the Nursing community, considering the Brazilian reality. PMID- 1297163 TI - [An organizational model of nursing service]. AB - This study approaches how important is a nursing organized service to achieve effectiveness. The author proposes a Nursing service organization model containing items such as: philosophy, goals, internal regiment and policies, divided in directive structure, budget human and material resources, teaching, research and nursing assistance. PMID- 1297164 TI - [Intracavity brachytherapy in uterine neoplasms]. AB - The growing use of intracavity treatment of uterine neoplasia has not been accompanied in the Brazilian literature by articles appropriate for day-to-day consultation. Based on this fact we endeavour to transmit in this paper our experiences related to this therapy technique. PMID- 1297165 TI - [Introducing the human existential dimension into a course on nursing fundamentals]. AB - The study consisted of one historical retrospect of how the course Fundamental of Nursing is being oriented in man focus and the of assistance of nursing given to him. It describes and analyses an experience which has been realized by teachers of course Fundamental of Nursing in the Nursing School of Ribeirao Preto at University of Sao Paulo. It consists of the philosophical approach about the man who we assist. Consolidate with the Heidegger's ideas, we introduce the man's notions of being-in-the-world-with-the-others, of hospital and disease world and the facets, enabling to see the man as sick, in his-being-sick, as the new perspective of comprehension of human existence. PMID- 1297166 TI - [The teaching of primary health care: diagnostic and educational evaluation by microcomputers]. AB - The study aims to explore the utilization of the Formative Evaluation by the microcomputer in the teaching of primary attention to the health. The experiment is composed of eight modules, programmed in Basic software "Formative Evaluation". For each module, a "Question Bank" with three sorts of feedbacks was organized. The sample includes 16 subjects. The results show that the Formative Evaluation by Microcomputer proportioned to the students a cognitive domain significantly higher than the traditional instruction. However, it didn't provide a significantly superior performance to the students who experienced this system. PMID- 1297167 TI - [Reproductive cycle of the pocket gophers Orthogeomys cherriei (Rodentia: Geomyidae) in Costa Rica]. AB - Pocket gophers (Orthogemys cherriei) is a pest in agriculture in Limon, Costa Rica; 232 animals were trapped in several farms. They reproduce continuously throughout the year. Adults of both sexes are found in reproductive condition at any time. The females produce at least 2 litters per year (1-4 newborns each). There is no correlation between position of testes and production of sperm. The position of the testes is not a reliable factor to establish the reproductive condition in males. There is a correlation between length of os penis (baculum) and length of the testes, irrespectively of its reproductive condition. These pocket gophers disperse above-ground. PMID- 1297168 TI - [Effect of corticosteroids on the congenital transmission of experimental toxoplasmosis]. AB - Female white mice with chronic toxoplasmosis were treated with cortisone acetate (3mg for each 25 g of body weight) 12, 8, 4 and 0 days before mating. Cortisone induces congenital transmission of T. gondii. PMID- 1297169 TI - [Cytotoxicity induced by Peruvian snake venom on fibroblasts of mice]. AB - The cytotoxic effect of venoms from six crotalinae Peruvian snakes (Bothrops atrox; B. brazili; B. pictus; B. barnetti; Lachesis m. muta y Crotalus durissus terrificus) was studied in an in vitro system of BALB/c 3T3 fibroblasts grown in Dulbecco modified minimal essential medium at 37 degrees C in a humidified atmosphere of 5% CO2-95% air. The viability of the cells was evaluated 24 hours after the treatment with the different venoms, using the method of exclusion of trypan blue. The six venoms produced cytotoxic effects at 24 hours on the 3T3 fibroblasts. The venom from B. atrox was the most potent (DE50 = 162 ng/ml) and that from B. barnetti the least (DE50 = 7182 ng/ml). PMID- 1297170 TI - Proximate composition of muscle of cage-raised red drum, Sciaenops ocellatus (Pisces: Sciaenidae), in Panama. PMID- 1297171 TI - Sexual differences in the brain catecholamine content in four species of tropical bats. AB - The catecholamines dopamine, norepinephrine and epinephrine were studied in the brains of male and female tropical bats of four species, with different feeding habits (insectivorous, frugivorous, omnivorous and pollen eater). They were trapped in a refuge at 18 degrees 24'24''N, 99 degrees 02'08''W with a mean annual temperature of 25.8 degrees C, in a tropical deciduous forest. The three catecholamines occur in both sexes of all four species, in levels which are statistically different among species as well as between sexes. Dopamine and norepinephrine levels were higher in males than females, but the opposite occurs with epinephrine. These findings suggest that changes in catecholamine levels are intimately involved in the reproductive pattern of the species studied. PMID- 1297172 TI - [Chemico-nutritional composition of meat of Strombus galeatus (Mesogastropoda: Strombidae)]. AB - Strombus galeatus samples were collected in Lagarto (10 degrees 06'N,85 degrees 48'W), Bahia Ballena (9 degrees 42'N,85 degrees 01'W) and Golfito (8 degrees 30'N,83 degrees 10'W) at the Pacific coast of Costa Rica. Individual weight ranged between 141.9 and 241.3 g (41.3-65.6% edible). Over 72% is water, 23% protein and 3% ash. The caloric content varied between 126.5 and 129 kcal/100g. Fat, crude fiber and carbohydrates contents were small. Mean ranges (%) in minerals were: 403.0-465 P, 233.5-315.7 Ca, 89.7-315.0 K, 122.3-145.5 Na, 217.5 266.3 Mg, 1.5-5.3 Fe, 2.0-8.7 Zn and 0.2-0.5 mg % Cu. As was not detected, and the Cd and Pb contents were 0.046-0.062 and 0.19-0.21 mg/kg, respectively. Concentrations of heavy metals in the meat are not toxic for humans. PMID- 1297173 TI - [Hematologic values and serum enzymes in horses inoculated with snake venoms for the production of antivenins in Costa Rica]. AB - Blood components were studied in six horses immunized with snake venoms for the production of polyvalent antivenom in Costa Rica. No significant changes in hemoglobin or hematocrit throughout the immunization period were observed, whereas a significant increment in total serum proteins occurred in the second half of the immunization process, probably due to an increased synthesis of immunoglobulins. There were no significant changes in creatine kinase, but a slight increment was detected in both transaminases, although they did not exceed normal limits. These findings suggest the absence of relevant tissue damage in skeletal muscle, cardiac muscle and liver. In agreement with these results, horses did not develop signs of systemic poisoning, presenting only minor alterations at the site of venom injection, such as oedema, abscesses and fistulas. The development of anti-phospholipase A2 antibody response showed a prominent individual variability, as previously described. PMID- 1297174 TI - Protective effect of a monoclonal antibody specific for an echovirus cellular receptor in human fibroblast and simian kidney cell lines. AB - We previously reported that infection of KB cells by echoviruses (EV) was inhibited by a KB-derived EV receptor murine monoclonal antibody (mAb 143). This antibody enabled the identification of a cellular receptor common to all echoviruses (with the exception of EV-22 and -23) and coxsackievirus (CV) A9, but different from the receptor of other picornaviruses. We now present results of cell protection assays conducted with human and simian cell lines different from the KB cell line used for production of mAb 143. When human embryonic lung fibroblasts were pretreated with 150 micrograms/ml of mAb 143, EV-11 and CV-A9 were completely inhibited (more than a 2-log difference compared to untreated cells). When the cell protection experiments were performed with Vero cells, the same results were observed with EV-33, but not with EV-22. The protection afforded human fibroblast cells by mAb 143 persisted for at least 5 days after 2 h exposure to 100 TCID50 of EV-11. These results suggest that EV receptors can be effectively blocked for prolonged periods in susceptible cells. PMID- 1297175 TI - Role of acylation of viral haemagglutinin during the influenza virus infectious cycle. AB - We investigated fatty acid residues bound to the haemagglutinin (HA) of type A influenza viruses by growing the viruses in permissive chick embryo fibroblasts (CEF) and in non-permissive HeLa-229 cells using a maintenance medium containing 3H-palmitic acid. Our results suggest that fatty acid acylation of the major viral glycoprotein may be an important prerequisite for the production of mature viral particles. Indeed, palmitoylation is found in infected CEF, but is completely lacking in non-permissive HeLa-229 cells infected by the same virus strains. We conclude that this type of post-translational modification of virus HA glycoprotein could be a general phenomenon regulating the maturation and budding of influenza virus. PMID- 1297177 TI - Continuous cell lines and immune ascitic fluid pools in arbovirus detection. AB - Successive experiments led us to use two cellular systems, MOS61 (Aedes pseudoscutellaris cells) and Vero cells, among the continuous cell lines recommended by the WHO Collaborating Center for systematic research and isolation of arboviruses. Virus detection in cell cultures is carried out with 7 mixtures containing 10 hyperimmune ascitic fluids made with the reference viruses. This technique enables the detection of 70 of the 80 arboviruses transmitted by mosquitoes in Africa and very easily detects arbovirus associations by using either monospecific or monoclonal immune ascitic fluids (dengue-1-2-3-4 and yellow fever viruses) used in the indirect immunofluorescence technique. PMID- 1297176 TI - Rift Valley fever epizootic in the central highlands of Madagascar. AB - Between February and April 1991, unusual numbers of bovine abortion around Antananarivo (central highlands, Madagascar) were reported by official veterinary services. Rift Valley fever (RVF) virus isolations were made from sixteen aborted foetuses and one dead calf in different foci. Using monoclonal antibodies, the isolated viruses were found to be different from the 1979 RVF strains isolated in Madagascar from mosquitoes and human laboratory infection, and closer to African RVF strains. In a bovine population--previously characterized by a negative or very low RVF antibody prevalence--a high prevalence of IgM antibodies (264/994: 26.5% positive) was revealed; the IgM prevalence in recently aborting females varied from 40 to 91%. Among 994 human sera tested by IgG-IFA (immunofluorescent antibody assay) and IgM ELISA, 8.2% and 4.5%, respectively, proved positive. A total of 11,371 mosquitoes (61% Culex antennatus) were collected in the epizootic areas and tested without any virus isolation. Extensive studies were conducted to determine the geographical extension and the impact of this epidemic on the highly susceptible livestock and human populations. PMID- 1297178 TI - Levels of IgM antibodies against dengue virus in Rio de Janeiro, Brazil. AB - The appearance and persistence of IgM antibodies were studied by MAC-ELISA in 926 confirmed cases of dengue virus type 1 infection. Assays performed on acute and convalescent patient sera revealed that IgM antibodies appeared during the early phase of disease (day 2) and persisted for three months after onset. MAC-ELISA proved to be a valuable early diagnosis test when compared with haemagglutination inhibition. PMID- 1297179 TI - [A day with Annie Le Maux, private practice nurse. Interview by Virginie Champion and Isabelle Lefevre]. PMID- 1297180 TI - [The psycho-prophylactic relation and prevention in maternity]. PMID- 1297181 TI - [Specificity in the management of a palliative unit for AIDS patients in the terminal phase]. PMID- 1297182 TI - [Infection, hygiene ... two adversaries in surveillance!]. PMID- 1297183 TI - [Open war against nosocomial infections]. PMID- 1297184 TI - [Home care services: team work is a necessity]. PMID- 1297185 TI - [Hyperuricemia and its complications]. PMID- 1297187 TI - ["Sophrology" and breathing]. PMID- 1297186 TI - [1,000,000th copy of the brochure: "infection by HIV and AIDS"]. PMID- 1297188 TI - [Paramedical school secretary: typist of assistant?]. PMID- 1297189 TI - [AIDS and mortality]. PMID- 1297190 TI - [Greenland--invitation to a dialog]. PMID- 1297191 TI - [Greenland--small and strong. Interview by Soren Palsbo]. PMID- 1297192 TI - [Greenland--what do you expect from Peqqissaasut Kattuffiat?]. PMID- 1297193 TI - [Greenland--send for reliable information. Interview by Soren Palsbo]. PMID- 1297194 TI - [Executive Board]. PMID- 1297195 TI - [Romania--one year later]. PMID- 1297196 TI - [ICN--practical solidarity with Indian colleagues]. PMID- 1297197 TI - [Local wages--a risk of breach in agreement]. PMID- 1297198 TI - [Russia--nurses in Saint Petersburg]. PMID- 1297199 TI - [Greenland--a new concept for health. Interview by Soren Palsbo]. PMID- 1297200 TI - [Nursing story--give yourself time]. PMID- 1297201 TI - [Research--mind and disease. Interview by Kirsten Bjornsson]. PMID- 1297202 TI - [Education. Health is good but we feel poorly]. PMID- 1297203 TI - [Cooperation--27 organizations with a common goal. Negotiations 93]. PMID- 1297204 TI - [Organization of regulations. A leash on private wage developments. Negotiations 93]. PMID- 1297205 TI - [Grief--a necessary crossing place]. PMID- 1297206 TI - [Storebaelt--nurses from the Sprogo oil platform. Interview by Mette-Marie Davidsen]. PMID- 1297207 TI - [Research--to be human. Interview by Grethe Kjaergaard]. PMID- 1297208 TI - [Infants with abstinence syndromes. A false start. Interview by Mette Fjordbo]. PMID- 1297209 TI - [Nursing story. On forbidden roads]. PMID- 1297211 TI - [Executive Board]. PMID- 1297210 TI - [Invitation to submit proposals. Nursing is interesting for the ISS]. PMID- 1297212 TI - [Local wages--on a collision course. Negotiations 93]. PMID- 1297213 TI - [Neonatology. Infants with abstinence syndrome]. PMID- 1297214 TI - [Prehospital treatment--it never becomes routine. Interview by Peter Skeel Hjorth]. PMID- 1297215 TI - [AIDS: physicians condemned in French hemophiliac scandal]. PMID- 1297216 TI - [Patient information--fear, hope and education. Interview by Kirsten Bjornsson]. PMID- 1297217 TI - [Patient information--patients must make decision. Interview by Kirsten Bjornsson]. PMID- 1297218 TI - [Community health nurses should give information on infant nutrition]. PMID- 1297219 TI - [Researchers' meet--leg work]. PMID- 1297220 TI - [New leave-of-absence offer. Parental and educational leave-of-absence payed by Unemployment Fund]. PMID- 1297221 TI - [Nursing story. Yankee bar]. PMID- 1297222 TI - [Danish Nursing Council--effort for a higher percentage of votes. Negotiations 93]. PMID- 1297224 TI - [Wage policy. Catalog of ideas for 1993 by Minister of Finance. Negotiations 93]. PMID- 1297223 TI - [Work environment. New committees can assure quality]. PMID- 1297225 TI - [Prehospital treatment. They must do it like we do it. Interview by Peter Skeel Hjorth]. PMID- 1297226 TI - [Wage policy. Professional borders should open up. Negotiations 93]. PMID- 1297227 TI - The cost of hospital stay for operable breast cancer. AB - The cost of the first hospital stay for operable breast cancer was deducted by analysing a random sample of 100 admissions to the National Institute of Cancer during the period January-December 1989. The aims of the study were: (1) to describe and calculate the cost component of the stay; (2) to analyse whether any procedure, service rendered or stage of the pathology might explain differences in the total costs of the stay; and (3) to acquire a better knowledge of the organizational aspects to be improved. With an average length of stay of 14.1 days, the overall total cost observed was 4.9 million lira (US $3.800, 1989 US dollars). A significant correlation between total cost and duration of stay was found (R2 = 0.982), while no or very little correlation was found between cost and the anatomical extent of disease (TNM stage) and different cost items (laboratory, imaging tests, operating room, etc.). Two homogeneous groups of cases were found: patients with quadrantectomy and patients with mastectomy. The cost of the latter was 40% greater than that of the former (P < 0.001) with a length of stay 52% longer (p < 0.001). This study does not concern the costs immediately following the stay, which namely are higher for the quadrantectomy because the radiotherapy outpatient procedures. Attention should be paid to reducing the length of stay, keeping waiting time for organizational procedures to a minimum during the stay. PMID- 1297228 TI - Descriptive epidemiology of stomach cancer in Ragusa, Sicily, 1981-1988. AB - An epidemiologic study was carried out on 475 incident cases of gastric cancer registered by the Ragusa Cancer Registry (Sicily) between 1981 and 1988. Distribution by sex, age, subsite, year of incidence, and survival was investigated. A reduction of incidence and mortality between 1981-84 and 1985-88 was observed in both sexes, and was more evident in males than in females. Survival was not significantly different for cancers of the various subsites. PMID- 1297229 TI - Morphogenesis of epithelial lesions in the lymphoid patches of Fischer 344 rats during cyclosporine-A-induced prolonged immunosuppression. AB - Alterations of intestinal lymphoid patches induced by cyclosporine A (CS-A) were studied in male Fischer 344 rats. Continuous treatment with CS-A (10 mg/kg b.w. by gavage daily) resulted in lymphocyte deficiency of the intestinal lymphoid patches followed by progressive replacement of the lymphoid tissue by cystic and glandular epithelial structures and single cells positive for epithelium associated immunohistochemical markers. Cessation of CS-A administration led to regression of the alterations and a moderate recovery of the lymphoid patches. Morphologic changes induced at the epithelial-lymphoid border may be a useful parameter to estimate immunotoxicity. PMID- 1297230 TI - Biologic relevance of elevated red cell adenosine deaminase activity in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria. AB - Red cell adenosine deaminase (ADA-RBC) activity in patients with myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria is significantly increased compared to that observed in normal controls. ADA-RBC activity is not related to fetal hemoglobin concentration, but it is significantly correlated with hemoglobin concentration at diagnosis and with the degree of morphologic dysplasia in the erythroid lineage. The results of our study suggest that the observed enzymatic abnormality may constitute a non-specific manifestation of the stem cell alteration that determines these disorders. PMID- 1297231 TI - Adjuvant radiotherapy of the pelvis with or without reduced glutathione: a randomized trial in patients operated on for endometrial cancer. AB - A randomized pilot trial was performed to evaluate the feasibility of administration of glutathione (GSH, 1200 mg, i.v.) as a protector in preventing diarrhea in patients operated on for endometrial cancer and submitted to adjuvant radiotherapy of the pelvis. Diarrhea occurred in 52% of patients in the untreated control group and only in 28% of patients in the GSH-treated group. Our preliminary data indicate that GSH administered before radiotherapy reduced the occurrence of diarrhea from oxidative damage to the intestinal mucosa. A large scale phase III study is required to obtain definitive conclusions on the protective potential of GSH. PMID- 1297232 TI - Mitomycin C and vindesine: an ineffective combination chemotherapy in the treatment of malignant pleural mesothelioma. AB - Twelve patients with malignant pleural mesothelioma were subjected to mitomycin C (MMC) and vindesine (VDS) chemotherapy (MMC 10 mg/m2, i.v., d 1; VDS, 3 mg/m2, i.v., d 1-8, every 4 weeks). No objective response was obtained; 3 (25%) patients had stable disease and 9 (75%) progression of disease. We conclude that MMC plus VDS is an ineffective combination chemotherapy in the treatment of malignant pleural mesothelioma. PMID- 1297233 TI - Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma. AB - On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil. PMID- 1297234 TI - Surgical and adjuvant radiation therapy of resectable retroperitoneal soft tissue sarcomas in adults. AB - Primary soft tissue sarcoma of the retroperitoneum is a rare disease. A series of 11 evaluable adult patients with retroperitoneal soft tissue sarcomas is reported. These patients were treated with complete surgery and adjuvant radiation therapy (total dose from 50 to 64 Gy) using an 18 MeV linear accelerator. After a median follow-up of 48 months (range, 6-84), 4 patients had a local-regional recurrence, 3 had distant metastases, and 4 died of progressive disease. Four-year estimated disease-free survival was 54.5% and overall survival was 70%. Treatment was well tolerated by most patients: 7 patients experienced moderate gastrointestinal toxicity, mainly nausea and diarrhea, during radiotherapy; 2 cases had weight loss > 15% at the end of the therapy; and chronic ileitis was observed in 2 cases. We conclude that adjuvant radiotherapy seems to reduce the incidence of local-regional recurrences in these patients. No radiation-induced irreversible injury was observed, but one young woman had amenorrhea after radiotherapy. Controlled clinical trials are warranted to define the role and effectiveness of adjuvant radiotherapy and/or chemotherapy in retroperitoneal soft tissue sarcomas. PMID- 1297235 TI - Single brain metastases from kidney tumors. Clinico-pathologic considerations on a series of 29 cases. AB - Twenty-nine cases of single cerebral metastases from renal carcinoma were the object of a retrospective and prospective study covering a period of 15 years (1975-1988). The best diagnostic means were NMR imaging with paramagnetic contrast medium and CAT scans after intravenous injection of a double dose of contrast medium. All patients underwent total surgical removal of the cerebral lesion. Radiotherapy was useful but had less influence on further reproduction than in metastases from tumors of other sites. The median survival was 28.1 months in patients who received radiotherapy and 23 months in the others. No significant difference in survival was found between the group of patients with unknown primary tumors and the other group with diagnosed primary neoplastic disease. PMID- 1297236 TI - Adjuvant therapy for primary breast cancer in a female patient affected by autoimmune liver disease: does it cure breast cancer and primary biliary cirrhosis? AB - Polychemotherapy (CMF or CMF-like regimens) is the treatment of choice in premenopausal breast cancer patients with 1-3 positive nodes. In clinical practice, patients with abnormal biochemical tests of liver function are usually excluded from this potentially curative methotrexate-containing regimen in order to avoid worsening of hepatic damage. On the other hand, recent reports have shown a beneficial effect of methotrexate in a particular autoimmune liver disease such as primary biliary cirrhosis. We discuss the case of a female patient with breast cancer and primary biliary cirrhosis whose biochemical tests of liver function and the titer of antimitochondrial antibody persistently improved after treatment with 3 cycles of CMF. In conclusion, we suggest that the CMF regimen is potentially useful in patients with breast cancer and primary biliary cirrhosis. PMID- 1297237 TI - Primary spinal epidural non-Hodgkin's lymphoma. The contribution of nuclear magnetic resonance imaging, therapeutic approach and review of the literature. AB - Primary spinal epidural lymphoma (Stage I) is diagnosed predominantly late after a long prodromal phase of local back pain resulting in spinal cord compression. The use of CT and NMR images in the early stage of investigation and their analysis may help to diagnose these cases prior to the appearance of neurologic deficit. We report on 2 patients who presented with prolonged localized back pain with sudden symptoms of spinal cord compression. CAT scan and NMR imaging demonstrated the characteristic appearance of lymphoma. Decompressive laminectomy supported the diagnosis. Radiotherapy treatment to the region of the non Hodgkin's lymphoma resulted in complete resolution. Thereafter, systemic chemotherapy with CHOP achieved a good response. PMID- 1297238 TI - Kaposi's sarcoma on a lymphedematous arm following radical mastectomy. AB - Chronic lymphedema predisposes for local immune incompetence, manifested by development of Stuart-Treves syndrome, Kaposi's sarcoma and fibroma-like lesions. A 91-year-old female with multiple cancers developed classic Kaposi's sarcoma on a chronically lymphedematous arm 26 years after radical mastectomy and irradiation of the involved axilla. The Kaposi lesion partially responded to electron beam irradiation. PMID- 1297239 TI - Bladder leiomyoma in pregnancy: a case report. AB - We herein report a rare case of an asymptomatic bladder mass seen during pregnancy in a young woman. A hypogastric mass was detected at antenatal checkup in the 7th month of pregnancy. The mass increased in size as the pregnancy went to term. Three months after normal delivery, she underwent surgery and a tumor arising from the bladder wall was excised completely. Histology showed a symplastic leiomyoma. PMID- 1297240 TI - Adrenal gland metastasis in osteogenic osteosarcoma. A radiological case report. AB - Adrenal gland metastases from osteogenic sarcoma are rare and an unusual pattern of relapse. The recognition of solitary metastases, particularly when located in uncommon sites is very important for subsequent treatment. The authors describe the radiological features of an adrenal metastases from osteogenic sarcoma. PMID- 1297241 TI - [Biologic quality of colostrum and calves from dairy cows injected with zinc during pregnancy]. AB - The effects of an administration of the Zindep inj. preparation (Biotika) were evaluated in pregnant dairy cows as exerted on specific weight, total protein (TP) content, total immunoglobulin (IgC) and albumin (ALB) contents in colostrum. These parameters were also followed: calf's health, live weight, leucocyte (Lc) counts, T-lymphocyte (T-Ly) counts, contents of TPs, IgCs and ALBs in the blood serum of calves. Zinc concentrations were determined in colostrum, milk and calf blood serum. Our observations included 16 dairy cows in the seventh month of pregnancy in the second lactation and their calves in the winter feeding season. Eight experimental dairy cows were treated with the Zindep preparation in form of an injection to the neck muscles at a dose of 3 mg Zn/kg live weight in the mid seventh month of pregnancy. Blood samples were taken from v. jugularis from all calves before their first drinking, on days 5, 15 and 30 of age. Colostrum, and/or milk samples were obtained by drawing of the colostrum or milk from the udder quarters within 60 minutes after parturition, on days 5 and 15 of lactation. Zn levels at birth were 16.48 +/- 2.67 mumol/l in experimental calves and 13.84 +/- 3.19 mumol/l in control calves. Zincaemia decreased slightly in both groups on days 5 and 15 of age, but it was insignificantly higher in calves coming from Zindep-treated dairy cows. Zn levels in the blood serum on the 30th day of age were 18.45 +/- 2.44 mumol/l in experimental animals and 15.73 +/- 3.11 mumol/l in control animals. Zn content in the colostrum of experimental cows was 2.40 +/- 0.42 mg/l and in the control it was 1088 +/- 0.52 mg/l (P < 0.05). On day 5 of lactation, Zn amounts in the milk of experimental dairy cows decreased to 0.95 +/- 0.12 mg/l and to 0.76 +/- 0.10 mg/l in the control (P < 0.01). Zn levels in the milk of experimental cows on day 15 of lactation were 0.95 +/- 0.13 mg/l and in the milk of control group they were 0.82 +/- 0.14 mg/l. Colostrum specific weight from zinc-treated cows was 1,067.86 +/- 0.75 g/cm3 and 1,056.8 +/ 13.53 g/cm3 in the control. TP and IgC concentrations were 137.81 +/- 38.11 g/l and 110.13 +/- 29.91 U ZST, respectively, in the colostrum of experimental group, and 105.98 +/- 32.02 g/l and 85.53 +/- 25.42 U ZST, resp., in control animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297242 TI - [Body weight and selected hematologic and biochemical parameters in calves fed various diets during milk feeding]. AB - The objective of the present paper was to obtain haematological and biochemical parameters of calves during their milk feeding. Another goal was to compare a current feed ration containing the commercial feed mixture Biosan with two alternative rations comprising skimmed milk and fat supplement. The effect of milk drink acidification and the effect of the physical form of fat added to skimmed milk were investigated. the calves were divided into six groups, by 6 to 8 calves each (P1-Biosan, PP1-acid variant, P2-skimmed milk+fat concentrate powder KMKS, PP2-acid variant, P3-skimmed milk+fat paste, PP3-acid variant). The highest average daily liveweight gains were recorded in calves fed on unacidified skimmed milk with fat paste supplement (1.074 kg)-Tab. I. The highest average daily liveweight gains were observed in calves fed on fat paste enriched milk drink (P3) while the calves administered milk with fat concentrate powder (P2) had only slightly higher average daily weight gains than the calves on Biosan diet (group P1). The growth of daily weight gains as a result of diets containing acidified milk (PP1 and PP2) is also a positive finding; this growth is even statistically significant in the former case (P < 0.05). The calves showed hypohaemoglobinaemia from the beginning of the experiment (51.3-69.0 g/l) and the low haematocrit value (0.29-0.43 l/l), Tab. II, while the plasma iron level was paradoxically high (Tab. V).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297243 TI - [The effect of culture media on bacteriocin production in various strains of bacteria]. AB - Some staphylococcus and enterococcus strains were used to investigate the effect of culture medium on bacteriocin production. Staphylococcus cohnii SC7, Staphylococcus sp. ZTJ 151, S. saprophyticus SS 877, Enterococcus faecium EF1 and E. faecalis EFG2 were isolated from the rumen wall and contents of lambs, calves and fallow deer, Enterococcus gallinarum EG10 and E. avium EA12 were isolated from the caecum of Japanese quail. The tested bacteria belong to producers with a wide antimicrobial effectiveness spectrum, they have low to medium adherence and urease activity (Tab. III). These culture media were used to test the effect of culture medium on bacteriocin production: nutrient agar no. 2 and VL agar enriched with 2% of glucose and lactose (ZAG, ZAL, VLG, VLL), agar for isolation of faecal streptococci (SA) and the base for blood agar no. 4 and no. 2 (KA4, KA2). The strains Streptococcus bovis AO 24/85 and Staphylococcus aureus Oxford 209 P were used as indicator bacteria. Tables I and II show the results of these tests. The tested strains produced the widest inhibition zones (6 mm) with both indicators on SA medium, and this indicates massive bacteriocin production. On ZAG medium, the zones of enterococci with the AO 24/85 strain were larger size than those of staphylococci, but the zones were dim. All strains with the 209P indicator produced dim zones of the 2mm size. The larger inhibition zones (2-5mm) in comparison with staphylococci were observed in enterococci on the ZAL medium with the AO24/85 strain. The production of tested strains was balanced on VLG agar with respect to the use of both indicators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297244 TI - [Inhibitory effects of organic acids and salts on selected micromycetes]. AB - Inhibitory effects of two fungistatic preparations (A and B) and of propionic acid were tested in a complete feed mixture for broiler chickens (starter mixture). The water content of this mixture was 25.4%, environmental temperature was 24 degrees C and relative air humidity 90%. Propionic acid, which has a high fungistatic effect, served as a standard. The composition of the preparation A was as follows: propionic acid, acetic acid, sorbic acid, citric acid and calcium propionate. The preparation B contained: sorbic acid, citric acid and calcium propionate. Examinations were performed in a naturally contaminated and subsequently sterilized (25 kGy) feed mixture; it was then infected with Aspergillus fumigatus, A. niger, A. parasiticus and Penicillium purpurogenum from the Collection of Animal Pathogenic Microorganisms, Brno. A. flavus, A. fumigatus, A. glaucus, Penicillium sp., Absidia corymbifera, Mucor sp., Rhizomucor pusillus were detected in the naturally contaminated feed mixture. The mycoflora which was found in the native substrate was resistant to both tested fungistatic preparations; and this resulted in mycelium growth from 7th day of incubation. The efficiency of the preparations A,B and of propionic acid in the feed mixture was identical at concentrations of 4 mg/kg, 7 mg/kg and 3 mg/kg, respectively, and their inhibitory effects were lowest at these concentrations (Fig. 2). A high water content in the nutrient substrate resulted in the rapid growth of fungi of the Mucorales species. The relative humidity of the environment (90%) and water content of tested samples affected markedly micromycetes growth in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297246 TI - [A computer program for toxico-chemical analysis using gas chromatography]. AB - A high probability of identification of substances containing nitrogen or phosphorus in their molecules is obtained by the original gas chromatographic (GC) system. It enables the reliability of positive identification in 98.43% of cases compared with the modern GC where for the chromatographic library spectrum of 200 substances the probability of identification of unknown substances is only 28.13%. GC system is based on the parallel configuration of the two capillary columns of different polarities connected to the one-column injector and the one nitrogen-phosphorus detector as well as the original computer program developed on the qualitative-logistic approach to interpretation of chromatographic parameters using only one reference substance. The computer program can perform positive logistic identification also in the case when the unknown substance is in the closest chromatographic vicinity, with quite different reference substances on both capillary columns. PMID- 1297245 TI - [The effect of fungal and yeast glucan and levamisole on the level of the cellular immune response in vivo and leukocyte phagocytic activity in mice]. AB - The level of cell-mediated immune response in vivo was investigated using the test of delayed hypersensitive reaction (DHR) to DNFB, along with the phagocytic activity (PA) of blood leucocytes in mice after subcutaneous implantation of fungal and yeast glucan and levamisol in dependence on the dose and administration schedule. The soluble form of fungal glucan (Pleurotus ostreatus) potentiated the DHR significantly at a dose of 10 mg/kg (but not at a dose of 50 mg/kg) while it was administered during DNFB sensitization (P < 0.05)-Tab. I and when its pre-medication effect was investigated (days -7 and -14; P < 0.05) with regard to the time of sensitization (Tab. II). The identical dose of glucan also had a positive effect (P < 0.05 or 0.01) on the percentual proportion of phagocytic cells (PC) reaching the maximum in the 2nd and 3rd week of investigation, as well as on the phagocytic activity index (P < 0.05; 3rd week) and percentage of neutrophil granulocytes (P < 0.05; 2nd week)-Tab. III. Yeast glucan (Saccharomyces cerevisiae) showed a potentiating effect on the DHR to DNFB only in the case of its pre-medication use; its soluble form was effective at both doses (10 mg and 50 mg/kg) in days -7 and -14 (P < 0.05), and its corpuscular form at a dose of 50 mg/kg on days -7, -14 and -21 (P < 0.05 or 0.01) Tab. II. PA parameters of blood leucocytes displayed a stimulative effect only on the PC percentage. The most significant effects in this case were observed in the soluble form (both doses) in the 2nd and 3rd week (P < 0.01 and 0.05, resp.) and in the insoluble form (both doses) in the 3rd and 4th week of observation (P < 0.05 and 0.01, resp.). An increase in the number of neutrophil granulocytes was significant in the 2nd (P < 0.05 or 0.01; corpuscular form) and 3rd week of the experiment (P < 0.01; soluble form)-Tab. III. Levamisol affected both investigated parameters (DHR and PA) only at a dose 20 mg/kg (10 mg/kg-no effect). Its potentiating effect on the DHR level was observed both for its administration at the time of sensitization (P < 0.05) and for its administration on days 7 (P < 0.05) and 14 (P < 0.01) before DNFB sensitization (Tabs. I and II). A statistically significant increase in PC was recorded in weeks 2, 3 and 4 (P < 0.05 or 0.01), a statistically significant increase in the number of neutrophil granulocytes in the 3rd week of investigation (P < 0.05). The phagocytic activity index was not affected. PMID- 1297247 TI - [Back ache in helicopter pilots]. AB - Due to low back pain (LBP) and harmful effects of flying, questionnaires were sent to 71 helicopter pilots of the experimental group, 22 mechanics helicopter flyers and to the control group of 28 air-traffic controllers. The prevalence of LBP was the highest in helicopter pilots, then in helicomechanics and air-traffic controllers (53%, 50% and 36%). Effects of exposure to vibration, body posture and working load have not contributed significantly to the occurrence of LBP. LBP has not lead to an important difference in the strength of the back musculature, body mass index and spondylosis, that is, scoliosis. The necessity of further study of LBP and maintaining of specific preventive measures are indicated. PMID- 1297248 TI - [Ultrasound, computer tomography and angiography in the diagnosis of dissecting aortic aneurysm]. AB - The findings obtained by ultrasound, CT and angiographic examinations of 75 patients with dissecting aortic aneurysms operated on at the M.M.A. are analysed. The aim of each particular method was to detect the presence of dissection, the aortic entrance tear and type of dissection. These findings were compared with the operative findings. On the basis of the analysis it has been concluded that the precision of the diagnosis obtained by angiography was 93%, by CT 74% and by ultrasound 69%. PMID- 1297249 TI - [Domiciliary rehabilitation of hemiplegics]. AB - Within six years 71 patients with hemiplegia were rehabilitated under home care. The patients were tested before and six months after the completion of rehabilitation. After rehabilitation 16 of 50 patients remained at the level of care while 34 moved to higher categories. Of 71 patients 13 was capable for all activities of daily living. PMID- 1297250 TI - [Decortication of the lung in the treatment of nonspecific pleural empyema]. AB - In the period 1986-1990 at the Clinic of Cardiac and Thoracic Surgery 86 patients with nonspecific pleural empyema were treated. There were 18 men and one woman, mean age of 35.6 years. Causes of empyema have been the following: pleuropneumonia (10 patients), chest trauma (2), iatrogenic pleural infection (2), spontaneous pneumothorax (2), mediastinitis (1) and pleural infection per continuitatem (2). The authors consider that decortication should be performed as early as possible, immediately after stabilization of acute signs of infection. The optimal time for surgery is from to six hours since the onset of the disease. PMID- 1297252 TI - [Preparation of tormentila tincture using ultrasound]. AB - The procedures of preparation of ultrasound tannin extraction for preparation of Tormentillae rhizome tincture are described and the comparison was made with maceration and biomaceration methods. The contents of the isolated tannin determined volumetrically was the same, but the time of ultrasound extraction is significantly shorter and also the procedure can be performed under field conditions. PMID- 1297251 TI - [Alveolitis in patients with sarcoidosis]. AB - In 20 patients with pulmonary sarcoidosis bronchoalveolar lavage (BAL) was performed. The cellular content was analysed and lymphocyte subpopulation was determined using monoclonal antibodies. The patients with more than 28% of BAL T lymphocytes are classified as patients with high intensity alveolitis (n = 8) and those with less than 28% of T lymphocytes as low intensity alveolitis (n = 12). Of the total number of BAL T lymphocytes in high intensity alveolitis CD 3+ T cells were 88.8 +/- 8.4% and in low intensity alveolitis 68.2 +/- 13.8% (p < 0.001). In high intensity alveolitis the number of CD 4+ T cells was increased and the number of CD 8+ T cells was decreased which caused the increased index CD 4:CD 8; 9.8 +/- 8.7. In low intensity alveolitis this ratio was 2.2 +/- 1.2. Effects of smoking were also analysed. In smokers the total number of BAL cells was higher 184.0 +/- 47.2 x 10(4) ml of BAL, and in nonsmokers 101.3 +/- 65.1 x 10(4) ml of BAL (p < 0.001). Smoking has no effects on the characteristics of the cellular elements and subpopulation of BAL lymphocytes in patients with sarcoidosis. In 7 patients T lymphocyte subpopulation in the peripheral blood were determined too. Patients with high intensity alveolitis had the increased index CD 4:CD 8 in the peripheral blood compared with low intensity alveolitis. PMID- 1297253 TI - [Magnetic stimulation of the motor cortex in healthy persons]. AB - In 49 healthy volunteers the motor cortex was stimulated transcranially by the intensive short magnetic field and the responses of the m. abductor digiti minimi (m. ADM) in 20 volunteers were recorded and of the m. tibialis anterior (m. TA) in 29 volunteers in relaxation and in mild contraction. In all volunteers by the electric stimulation of the ulnar nerve in the region of the wrist and the peroneal nerve in the region of the fibular capitulum there have been measured the F wave latency, distal latency of M responses and the conduction time of the peripheral motor neuron has been calculated. The difference between the latency of m. ADM and n. TA responses and the conduction time of the peripheral motor nerve represented the central motor conduction time from the motor cortex to the motor neurons of the anterior horns of the spinal cord (C8 and L4 segments). The normative values of the absolute latencies of the muscle responses and the central motor conduction time in the relaxed and contracted muscle are calculated as well as the normatives of the normal differences in latencies and the central motor conduction time between the left and right side of the same subject. PMID- 1297254 TI - [Effects of sodium valproate in a model of penicillin epilepsy in rats]. AB - Effects of sodium valproate in penicillin-induced epilepsy in rats have been described. To one group of rats penicillin was given I.P. (10(6) IU/kg) and to the another one it was given I.C. (100 IU). After development of grand mal sodium valproate was given I.P. to all rats except the control group. In the group receiving I.C. penicillin it has come to cessation of individual discharges and grand mal after valproate application. In the group receiving I.P. penicillin, valproate prevented only grand mal while individual discharges remained. It is obvious that much higher doses of penicillin are necessary for the development of the epileptic model if penicillin is given I.P. PMID- 1297255 TI - [Relation between the mind and body in disease]. PMID- 1297256 TI - [Exposure of the general population to electrical and magnetic fields in the environment]. PMID- 1297257 TI - [The phenomenon of "scapegoating" within the family]. PMID- 1297258 TI - [Angiomyolipoma--3 case reports]. PMID- 1297259 TI - [Benign symmetric lipomatosis of the neck]. PMID- 1297260 TI - [Myocarditis caused by influenza viruses]. PMID- 1297261 TI - [Health in Sweden. Sweden ought to have a Minister of Public Health. Interview by Jan Thomasson]. PMID- 1297262 TI - [Health in Sweden. Public health is a part of members' normal activities. Interview by Jan Thomasson]. PMID- 1297263 TI - [SHSTF supports health project on West Bank. Interview by Jan Thomasson]. PMID- 1297264 TI - [3-year education for Swedish nurses approved in the EEC]. PMID- 1297265 TI - [Nursing homes becomes cooperative. Interview by Jan Thomasson]. PMID- 1297266 TI - [Proposal for new regulations for the National Social Welfare Board. Supervision should apply to all health and nursing care]. PMID- 1297267 TI - [Proposal for new regulations for the National Social Welfare Board. All is well with supervision over all health and nursing care. Interview by Jan Thomasson]. PMID- 1297268 TI - [Effective hospital pins their faith on nurses]. PMID- 1297269 TI - [SHSTF in Vasterbotten: we cooperate with the thorax hospital's management. Interview by Carina Roxstrom]. PMID- 1297270 TI - The microbiologist and biological defense research. Ethics, politics, and international security. Introduction. PMID- 1297271 TI - The 1991 Persian Gulf War: implications for biological arms control. PMID- 1297272 TI - Ethics and biological defense research. PMID- 1297273 TI - The biological weapons convention and the researcher. PMID- 1297274 TI - The legality of the biological defense research program. PMID- 1297275 TI - Confronting biological threats to international security: a biological hazards early warning program. PMID- 1297276 TI - Narrowing the zone of uncertainty between research and development in biological warfare defense. AB - Although "research" is not prohibited by the Biological Weapons Convention, States Parties to the Convention have maintained the spirit of the Convention in actions relating to research. The confidence-building measures agreed to at RC2 refer to research facilities, publication of research results, and promotion of contacts between scientists engaged in research related to the Convention. However, assessment of basic research on biological agents is not a productive way to distinguish an offensive from a defensive program. Additionally, if a country were to initiate a biological weapons program, basic research on biological agents may not be necessary. For example, the extensive published research on Bacillus anthracis, both as a cause of anthrax in cattle and other species and as a biological-warfare agent, would enable any motivated group or nation to initiate a biological weapons program that could immediately advance to the development and scale-up stages. Research on biological agents for offensive purposes would be characterized by activities such as selection for growth, virulence, and toxin production; improving stability under varying environmental conditions; and selection of strains that might overcome existing means of prophylaxis and treatment. A biological program with an offensive intent would in most cases be characterized by evidence of development efforts in mass production and dissemination, which are often agent-specific. Thus, an assessment of development may distinguish offensive from defensive programs. If a country were to initiate a biological weapons research program, and were willing to risk worldwide condemnation should existence of such a program become known, it is likely that such a program would include development and production capabilities. If a country were not committed to production capability, there would be no rationale for an offensive biological research that would bring worldwide condemnation. Critics of the U.S. Biological Defense Research Program have suggested that the program could easily and quickly be turned into an offensive effort. To accomplish this, however, we have to assume that all military personnel, including the civilians employed by the Department of the Army, are unethical and willing to break the law and run the risk of placing the U.S. in a noncompliance status. The Army is under constant scrutiny by governmental agencies, by visiting scientists, by audiences at scientific meetings, by scientists who review manuscripts for publications, by news media, and by private citizens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297277 TI - Civilian control of biological defense research. PMID- 1297278 TI - DoD-sponsored virus vaccine development: an investigator's perspective. PMID- 1297279 TI - Japanese biological warfare research on humans: a case study of microbiology and ethics. PMID- 1297280 TI - Biological defense and industry. PMID- 1297281 TI - Biological warfare: role of scientific societies. PMID- 1297282 TI - Biological warfare allegations: the Korean War case. PMID- 1297283 TI - Bioweaponry and "life-sciences liberalism". PMID- 1297284 TI - History of biological warfare: catapults to capsomeres. PMID- 1297285 TI - [Is myocardial revascularization always indicated and useful?]. PMID- 1297286 TI - [Feasibility, indications and immediate results of direct angioplasty without thrombolysis during the acute period of myocardial infarction]. AB - Between June 1988 and November 1991, 64 out of 200 consecutive admissions (32%) before the 6th hour of myocardial infarction underwent angioplasty of first intention. Fifty men and 14 women (average age 62 +/- 11 years) benefitted from this 24 hour emergency interventional cardiology service. The indication was formal in 22% of patients because of a contra-indication to thrombolysis (N = 40) or cardiogenic shock (N = 4); in 6%, the choice was logical because of diagnostic uncertainty (N = 12); it was a deliberate choice in 4% of cases (N = 8). Successful angioplasty was defined as reperfusion of the occluded artery without circulatory delay or > 50% residual stenosis. Arterial recanalisation was attempted in all patients (associated with intraaortic balloon pumping in 3 cases) and was successful in 59 patients (92%) within 231 +/- 100 minutes of the onset of chest pain and within 49 +/- 29 minutes of hospital admission. The outcome was uncomplicated without any other intervention in 81% of patients (48/59). Three reocclusions were observed, two of which were symptomatic and treated successfully by repeat emergency angioplasty. Six surgical revascularisations were necessary (2 emergency, 4 secondary). One major complication related to the angioplasty was observed (haemopericardium). Global hospital mortality was 9% (6/64): three of the 4 patients admitted in cardiogenic shock, 3 of the 40 high risk patients with contra-indications to thrombolytic therapy, none of the 20 patients considered to be at low risk (uncertain diagnosis and deliberate choice).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297287 TI - [Doppler echographic evaluation of mitral valve stenosis with atrial fibrillation. Construction of a nomogram]. AB - Doppler echocardiographic evaluation of mitral stenosis is often difficult in patients with atrial fibrillation. Sixteen patients were examined by transthoracic Doppler echocardiography and the relation between the variations in transmitral end diastolic pressure gradient and the length of the corresponding cardiac cycles was analysed. Mitral valve surface area (1.65 +/- 0.73 cm2) was determined by the pressure half-time method. The end diastolic transmitral pressure gradient was calculated from the simplified Bernouilli formula applied to end diastolic mitral flow velocity. In each patient, a linear relationship was observed between the end diastolic mitral gradient and the corresponding RR interval. The slope and intercept of the graph correlated significantly to mitral valve surface area (r = 0.72, p < 0.002 and r = 0.93, p < 0.00001, respectively). Using regression equations describing these correlations, it has been possible to construct a nomogramme indicating mitral valve surface area as a function of mitral end diastolic pressure gradient and the duration of the corresponding RR cycle. This nomogramme facilitates Doppler evaluation of mitral stenosis in atrial fibrillation. PMID- 1297288 TI - [Long-term prognosis of congenital atrioventricular block]. AB - The aim of this study was to assess the long term prognosis of congenital atrioventricular block (AVB). From 1965 to 1990, 42 cases of congenital AVB (22 antenatal or natal diagnoses and 20 presumed congenital AVB according to Yater's criteria). The AVB was isolated in 28 cases and associated with cardiac disease in 14 cases (8 of which were corrected transposition of the great arteries). The average age of the patients was 14 years (range 32 years to 18 months) at the time of the study. There was a clear female predominance (64%). Maternal connective tissue disease was present in 18% of cases (in the group of children born after 1977 when maternal connective tissue diseases was systematically looked for). Cardiac failure was present in 10 cases (8 with associated AVB); syncope and sudden death were observed in 11 cases. The indication for pacemaker therapy was the presence of poor prognostic factors: syncope, poorly controlled cardiac failure, low heart rate, increased QRS duration, prolonged QTc, infrahisian AVB, long pauses or arrhythmias on Holter monitoring. The only significant prognostic factors in this series were a previous history of syncope, increased QRS duration and a QTc of over 0.45 seconds. Fourteen patients were paced (endocavitary pacing only from 1981), usually in the DDD mode: 8 for syncope, 2 for cardiac failure, 4 for a poor prognostic factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297289 TI - [Clinical and hemodynamic prognosis after tricuspid valve replacement with bioprosthesis]. AB - Between 1974 and 1990, 58 patients underwent tricuspid valve replacement with a porcine bioprosthesis (Hancock 42, Carpentier-Edwards 16) in the course of polyvalvular replacement (double 21, triple 37). Early postoperative mortality was 12%: 16 patients died secondarily, usually of cardiac causes. The actuarial survival (1 patient lost to follow-up) was 81 +/- 11% at 5 years and 60 +/- 17% at 10 years. Two patients were reoperated for dysfunction of a Hancock bioprosthesis, 11 and 15 years after implantation. At long-term, with an average follow-up of 108 +/- 48 months, 82% of survivors (28/34) were clinically improved. Doppler echocardiography was performed in 29 patients in February 1991. In 21 cases, with a follow-up of 88 +/- 40 months, the bioprosthesis was normal with an average diastolic transprosthetic pressure gradient of 3.8 +/- 1.7 mmHg. In 7 patients followed up for 129 +/- 40 months (p < 0.05) moderate dysfunction of the Hancock prosthesis was observed with a mean diastolic pressure. Severe dysfunction of a Hancock prosthesis was observed in 1 case. Fixed pulmonary hypertension was noted in 11 cases and was associated with a poor clinical result and a raised mean diastolic transprosthetic pressure gradient. The durability and haemodynamic performance of tricuspid porcine bioprostheses are satisfactory in the long term. Prosthetic dysfunction is correlated to the duration of implantation of the bioprosthesis and to persistent pulmonary hypertension. PMID- 1297290 TI - [P wave changes and atrial fibrillation after implantation of VVI type pacemaker]. AB - The P waves of patients with VVI pacemakers were compared with those of DDD pacemakers at implantation and then regularly for 5 years. A certain number of cardiac pathologies are known to cause P wave changes. The incidence of atrial fibrillation (AF) was much higher in VVI than in DDD patients. In the VVI group, the incidence was much greater in patients paced for sinus node disease than in patients paced for AVB. Analysis of sinus P wave characteristics in 320 patients with VVI pacemakers shows progressive abnormalities of atrial function with time. The expression of this atrial dysfunction is a statistically significant prolongation of the P wave in V1 and dII and of the terminal part of the P wave in V1. The factors responsible for this abnormality and which favours the occurrence of AF are quasi-permanent pacing, the presence of retrograde conduction and an abnormality of atrial activation at the time of implantation. PMID- 1297291 TI - [Left ventricular dilatation after primary transmural anterior myocardial infarction. Influence of the percentage of akinesia on echocardiography]. AB - The aim of this study was to determine whether the percentage of akinesia on echocardiography during the acute phase of transmural anterior myocardial infarction could predict secondary left ventricular dilatation. The study group comprised 24 patients (18 men and 6 women) with an average age of 59 years. The patients underwent two echocardiographic examinations, the first during the acute (< 72 hours) phase and the second, 6 months later. Ventricular volumes were calculated by the ellipse monoplane method in the apical 4 chamber view. The percentage of akinesia was defined as the ratio between the length of the akinetic segment and the left ventricular end diastolic perimeter in the apical 4 chamber view. An increase in end diastolic volume (83 +/- 25 vs 62 +/- 18 ml/m2; p < 0.01) and in end systolic volume (51 +/- 27 vs 34 +/- 11 ml/m2; p < 0.01) was observed 6 months after infarction without a significant change in ejection fractions (42 +/- 17% vs 44 +/- 10%). The percentage of akinesia in the acute phase was > 30% in 15 patients (Group I) and < 30% in 9 patients (Group II). The increase in ventricular volumes at 6 months after infarction was significant in Group I (p < 0.02) but not in Group II. At 6 months after infarction, the end systolic volumes were greater (60 +/- 27 vs 37 +/- 22 ml/m2, p < 0.5) and the ejection fractions were lower (35 +/- 13% vs 53 +/- 18%, p < 0.01) in Group I than in Group II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297292 TI - [Efficacy and tolerance of 2 new percutaneous vena cava filters. A prospective study in 80 patients]. AB - Eighty consecutive patients with an average age of 66.5 +/- 16 years were reviewed 3 and 9 months after implantation of two new percutaneous vena caval filters (Filcard, Cardial) in order to evaluate their efficacy and tolerance. The indications were: a contra-indication to anticoagulants in 19 cases, recurrent pulmonary embolism under anticoagulant therapy in 22 patients, chronic cor pulmonale in 4 patients; finally, in 35 cases, the filter was implanted prophylactically for a "floating" or extensive ilio-caval thrombosis under anticoagulant therapy or in high risk patients: severe cardio-pulmonary failure, malignant disease, massive pulmonary embolism with a contra-indication to fibrinolytic therapy. All implantations were performed by the jugular approach with no local or general complications apart from one pericaval haematoma with a favourable outcome. Cavography and opacification of the renal veins was carried out systematically during implantation. All patients underwent clinical examination, antero-posterior and lateral X rays of the filter, pulmonary scintigraphy, antero-posterior and lateral cavography, a CT scan of the filter, Doppler ultrasonography and rheoplethysmography of the legs 3 months after implantation. At 9 months, clinical examination, abdominal X rays and rheoplethysmography were repeated. There was 100% follow-up at 3 and 9 months. The complications observed at 3 and 9 months were: 5 cases of malposition (6%), 3 recurrent pulmonary emboli (4%), 9 recurrent venous thromboses (13%), 4 vena caval thromboses (5.7%), 7 thrombi caught in the filter (10%), 27 perforations of the vena cava (38%), 3 over 30 degrees tilts of the filter (4%) and 22 migrations (31%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297293 TI - [Influence of exercise on the permeability of accessory pathways and supraventricular arrhythmia in Wolff-Parkinson-White syndrome]. AB - The influence of adrenergic stimulation on the effective anterograde refractory period of the accessory pathways and on supraventricular arrhythmias, was studied in 20 patients (average age 38 +/- 16 years) with an untreated permanent Wolff Parkinson-White syndrome and a resting anterograde refractory period < or = 400ms. Repeated electrophysiological studies with a single endocavity catheter positioned near the atrial pole of the accessory pathway were performed under basal conditions and during a standardised exercise test on a bicycle ergometer. The effective anterograde refractory period of the accessory pathway, the length of the tachycardia cycle during reciprocating orthodromic tachycardia, the average heart rate, the percentage of preexcited QRS complexes during induced atrial fibrillation, were measured in all patients under basal conditions and at the peak of exercise. Exercise significantly reduced the anterograde refractory period of the accessory pathway (287 +/- 49 ms at rest versus 238 +/- 24 ms on exercise: p < 0.001), the cycle of orthodromic tachycardia (302 +/- 32 vs 260 +/- 22 ms p < 0.001), the minimal R-R interval (270 +/- 65 vs 227 +/- 46 ms: p < 0.05) and % of preexcited QRS complexes (75 +/- 33 vs 51 +/- 39: p < 0.05) in atrial fibrillation whilst increasing the average heart rate (165 +/- 42 vs 202 +/- 39 bpm: p < 0.02). Adrenergic stimulation significantly improves anterograde conduction in the accessory pathway. The reduction in the % of preexcited QRS complexes in atrial fibrillation could indicate a preferential action of catecholamines on the nodo-hisian pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297294 TI - [Results of coronary-angiographic evaluation after endocavitary fulguration of the accessory pathways]. AB - Left ventricular aid coronary angiography was performed systematically in 32 consecutive patients (average age 34 +/- 16 years) to assess the potential risk of coronary and myocardial lesions after high energy catheter ablation of an accessory pathway. The control was performed 2 to 6 months after the procedure in 30 patients and as an emergency immediately after the procedure in 2 patients because of prolonged ST segment elevation in 1 and an echocardiographic abnormality in the other. The catheter ablation was performed by a right heart approach in 19 patients and by retrograde catheterisation of the left heart in the other 13. The average number of shocks delivered was 3.6 +/- 2.4 in 1.8 +/- 1.2 session with an average energy of 632 +/- 220 joules. The global success rate was 88%, 70% complete successes and 18% clinical successes. The left ventricular and coronary angiographies were normal in 31 patients, including the 2 patients investigated as an emergency. On the other hand, one totally asymptomatic patient in whom a left lateral bundle of Kent had been ablated 2 months previously by a retrograde transaortic approach, had a large pseudo-aneurysm of the left ventricular posterior wall and coronary angiography showed a fistula between the first lateral branch of the circumflex artery and the left ventricle. At surgery, a localised rupture of the mitral annulus was confirmed. Two factors may at least partially explain this complication: the quantity of energy delivered (1,000 joules) in a single session to a limited area, and the site of ablation on the ventricular side of the mitral annulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297295 TI - [Interference between cardiac pacemaker and electromagnetic anti-theft devices in stores]. AB - Electromagnetic anti-theft devices in shops comprise large diameter magnetic induction coils between which the shoppers pass. This study was undertaken with a simulator to assess the behaviour of different models of single and double chamber pacemakers when exposed to 6 stereotyped and repetitive situations of 4 different electromagnetic anti-theft devices. Of the 35 pacemakers tested, 25 developed serious dysfunctions: 14 long-lasting inhibitions (over 3 seconds), 2 stimulations at maximal frequency, 2 electrical bradycardias and 2 permanent reprogramming. These dysfunctions due to electromagnetic interference are observed in old or modern, monopolar or bipolar pacemakers, and seem to be influenced by the amplitude and complexity of the signals emitted by the detectors. These observations justify a clear signalization warning pacemaker patients of a potential danger. PMID- 1297296 TI - [Comparison of prognosis and treatment of myocardial infarction in Haute-Garonne between 1986 and 1989. MONICA project, Toulouse]. AB - The aim of this study, based on the data of the MONICA register in the Haute Garonne, was to compare the prognosis and treatment of myocardial infarction between 1986 (253 cases) and 1989 (248 cases). The clinical features of these infarcts were comparable except for the previous history of ischaemic heart disease which was less common in 1989 (34.7% in 1986, 25.9% in 1989; p < 0.05). The 28th day mortality decreased from 8.4% in 1986 to 3.6% in 1989 without attaining statistical significance. The pre-hospital management was the same during the two periods of the study, with 67.6% of patients admitted to hospital before the 6th hour. Hospital care in 1986 and 1989 consisted of 5 days in the intensive care unit and lasted 14 days. Treatment changed considerably from 1986 to 1989. There was a higher incidence of platelet antiaggregant prescriptions (47.4% in 1986 and 80% in 1989; p < 0.001), of betablocker prescriptions (30.8% in 1986 and 47% in 1989; p < 0.05) and fibrinolytics (27.8% in 1986 and 52% in 1989; p < 0.01). Invasive procedures such as coronary angiography (83.5% in 1986 and 94% in 1989; p < 0.05), coronary angioplasty (20.3% in 1986 and 53.5% in 1989; p < 0.01) were undertaken in the majority of cases. The MONICA-Toulouse project shows a reduction in mortality and an increase in the use of therapeutic methods known to be effective in the reduction of mortality in myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297297 TI - [Intravenous thrombolysis by recombinant plasminogen activator (rt-PA) in unstable angina. A randomized multicenter study versus placebo]. AB - Fifty patients (38 men) with unstable angina pectoris defined by: pain lasting > 15 minutes+percritical electrocardiographic changes+significant coronary narrowing on coronary angiography (Coro 1) performed within 24 hours, were treated in a double blind protocol with rt-PA (n = 25) 100 mg/90 minutes (10 mg bolus + 90 mg/90 minutes or placebo (n = 25). All received effective intravenous heparin and intravenous nitrates. Calcium antagonists and betablockers were prescribed in half the cases. Aspirin (100 mg orally per day) was prescribed after control coronary angiography (Coro 2) performed 24 +/- 6 hours after starting treatment. Qualitative and quantitative analysis (CAESAR system) was centralised. There were no differences in the angiographic findings between the two groups. Intracoronary thrombosis was observed in 43% (rt-PA) and 44% (placebo) in Coro 1 and in 17% and 28% in Coro 2. The incidence of myocardial revascularisation procedures was similar in the two groups: angioplasty: 12 (rt PA) and 13 (placebo); coronary bypass surgery: 5 (rt-PA) and 6 (placebo). Seven patients developed myocardial infarction (5 rt-PA, 2 placebo), one of whom died of cardiogenic shock (placebo). Eighteen patients had haemorrhagic complications (14 rt-PA, 4 placebo; p < 0.002) mainly at the puncture sites (12/14, 3/4). Spontaneous haemorrhage occurred in 7/25 (28%) of patients on rt-PA (haematuria 3, gastrointestinal haemorrhage 2, haematuria + gastrointestinal haemorrhage 1, epistaxis 1) and in 1/25 patients on placebo (gastrointestinal haemorrhage) This study shows that intravenous thrombolysis with rt-PA in severe unstable angina pectoris doe not modify the clinical outcome or the angiographic lesions but exposes patients to a high risk of haemorrhagic complications. PMID- 1297298 TI - [Diverticulum of the right atrium. A case report and review of the literature]. AB - Congenital atrial diverticula are rare, especially those involving the right atrium. This condition was observed in a 52 year old man who presented with palpitations. The diagnosis was made by two-dimensional echocardiography and confirmed by CT scan, magnetic resonance imaging and angiography. In the absence of significant invalidity, no treatment was recommended. Only three other cases of this condition have been previously reported, all of which were referred for surgery for thrombotic complications, arrhythmias and cardiac failure. Anatomo pathological analysis showed different appearances: fibrous tissue and lipomatous degeneration. In the absence of associated heart disease, these aneurysms are probably congenital. PMID- 1297299 TI - [Mediastinal hemangiopericytoma. Apropos of a case]. AB - The authors report a new case of hemangiopericytoma in an elderly man. An asymptomatic mediastinal mass was found on a routine chest film. C.T. guided fine needle biopsy was diagnostic. These rare lesions are clinically and radiologically aspecific and require pathologic proof. The value of percutaneous biopsy before therapeutic decision is emphasized. PMID- 1297300 TI - [Atrioventricular block at nodal and infrahissian level during atrial tachycardia. Apropos of a case]. AB - The authors report the case of a patient with atrial tachycardia and surface electrocardiographic signs of left anterior hemiblock and complete right bundle branch block with 10/3 atrioventricular block. The regularity of the RR intervals which were an exact multiple of the atrial cycle suggested the absence of a Wenckebach phenomenon. The sequence of atrioventricular conduction cannot be explained by classical models of intranodal conduction. Endocavitary recordings confirmed this hypothesis. They showed block at 2 levels: supra- and infrahisian. The suprahisian block functioned in the 2/1 mode and the infrahisian block in the 5/3 mode without incremental conduction distal to the His potential before the apparition of block. A double zone of intrahisian block could explain the observed sequence of atrioventricular conduction. The absence of Wenckebach phenomenon on the surface ECG during tachycardia could be a sign of infrahisian block. The authors suggest that the association of this sequence of atrioventricular conduction with intraventricular conduction defects is a formal indication for electrophysiological studies. PMID- 1297301 TI - Comparison of energy deposition and utilization of feedstuffs and rations between growing and adult pigs. AB - The effect of energy deposition and the utilization of feedstuffs and rations were compared between growing and adult pigs. The good agreement in the data leads to the conclusion, that the energy deposition effect of feedstuffs and rations in growing pigs can be estimated with an equation based on measurements in adult pigs. Exceptions are feedstuffs which are digested bacterially to a relatively high part in the large intestine, as e.g. sugar beet pulp, raw potatoes or similar feed. PMID- 1297302 TI - [The energetic utilization of rations with steamed potatoes in growing swine]. AB - The energetic utilization of rations with steamed potatoes (40 and 50% of DM of ration) was measured in 8 growing pigs, live weight 30-70 kg by means of respiration experimental techniques. The experiments were carried out using the difference method (3 periods feeding basal diet and 3 periods feeding basal diet plus potatoes). The digestibility of energy of the steamed potatoes amounted to 94%, that of organic substances 96% and that of crude protein 77%. The metabolizable energy amounted to 16.1 and the energy deposition to 12.0 MJ/kg DM of steamed potatoes, 74.5% utilization respectively. The results in growing pigs are very similar to the results in adult pigs. PMID- 1297303 TI - Effect of feedborne fluorine intoxication on broiler chicks' performance, biochemistry, physiology and pathology. AB - Feeding broiler chicks on graded levels of fluorine (0, 25, 125, 625 and 3125 ppm F) from NaF for 4 weeks (4-7 weeks of age) resulted in various alterations which depended on the level of contamination. The main changes included poor growth and feed conversion, high mortality rate, disorders of bone formation, decreased relative weights of pituitary, adrenal, heart, liver, spleen, lungs, kidneys and gizzard and changes in intestinal dimensions. Also, the biochemical tests revealed other kinds of physiological disfunction mainly in the form of anaemia (low haematocrit, haemoglobin, total protein, albumin and globulin fractions), intoxication (increased methaemoglobin), nephrotic (raised phosphorus and magnesium) and hepatic (elevated lipoproteins and lowering enzymatic activity) disfunctions. The general observations and postmortem examination confirmed also the biochemical findings which revealed the harmful effect of feedborne-fluorine intoxication in broiler chicks. PMID- 1297304 TI - The quality of meat of lambs fed with feeds containing lasalocid. AB - The aim of the research was to determine the quality of meat of lambs fed with feeds containing lasalocid. It was ascertained that lasalocid added in the quantity of 50 mg per animal and day to the feed during the whole period of fattening considerably increased the protein content in the longest back muscle in lambs. The addition of 50 mg lasalocid to the feed considerably lowered the fat content in the muscle. The muscle of lambs receiving 50 mg of lasalocid had the best water binding capacity and thus was most suitable for the production purposes. Lasalocid influenced significantly and advantageously the intensity of colour of the muscle. PMID- 1297305 TI - [The significance of the mycotoxins desoxynivalenol, zearalenone and ochratoxin A for agricultural domestic animals]. AB - Mycotoxins are metabolic products of mycotoxins which have various chemical structures and show various toxic effects. Deoxynivalenol (vomitoxin) is an important economic factor in pig production due to growth depression and suppression of the immune system. Previous studies have shown that the 1-ppm limit in the sole feed for pigs should not be exceeded. Studies of methods of detoxification have as yet not produced conclusive results. Zearalenone has an tolerable effect and may lead to fertility disturbances on the oestrogen production in pigs and can cause remarkable economic damage even in the ppb range. Recommendations of upper limits cannot be made on the basis of the available results. The kidney toxin ochratoxin A is of importance in pig and poultry breeding and--due to its accumulation in the tissue--represents a possible source of danger to man. Since a possible carcinogenic effect of the toxin cannot be excluded, its content in animal rations should be kept as low as possible. For ruminants mycotoxins as a whole do not represent a particular source of danger as these substances can be degraded or converted by rumen flora. PMID- 1297306 TI - Digital photoplethysmography in the diagnosis of traumatic vasospastic disease. AB - By means of the photoplethysmographic method including the cold test, skin blood flow was recorded in the fingers of 42 chain-saw operators and 36 control subjects. The essential difference between the groups pertained to the height of the pulse wave amplitude after the cold test and to the fall in amplitude expressed as a percentage of its initial value. A limit of a 90% fall in amplitude after the cold test is proposed as a criterion for differentiating a normal from a pathological vasospastic reaction. A fall in amplitude is correlated with the intensity of subjective disorders, i.e. the attack of vibration-induced white fingers. The obstructive form and loss of amplitude of the pulse wave form are accepted as pathological. PMID- 1297307 TI - [Potential genotoxic effects of cytostatics in occupationally-exposed persons]. AB - The aim of the study was to determine possible mutagenic implications of occupational exposure to cytostatic agents. Twenty-one nurses handling antineoplastic drugs and a matching control group were examined. The conventional method for testing chemical mutagens, that of sister chromatid exchanges, SCE, was used. Although the results obtained in the exposed group did not significantly differ from those obtained for the controls, wide ranges of SCE values observed among the medical personnel handling cytostatic drugs confirm the suspicion of the genotoxic effect of those agents. PMID- 1297308 TI - [Late changes in renal function after lead poisoning and chelation therapy]. AB - Glomerular filtration rate was examined by determination of creatinine clearance in 22 adult males with a past history of lead poisoning. Eighteen subjects had been poisoned after many years of occupational exposure to lead and four had been poisoned by ingestion of alcohol beverage kept in lead-glazed pots. Seventeen subjects were treated with the chelating agent calcium-disodium-edetate (CaNa2EDTA), the remaining five received no treatment. The aim of the study was to examine the delayed effects of lead poisoning on kidney function and the possible difference in functional impairment between the treated and the non treated subjects. The results obtained demonstrated a significantly reduced glomerular filtration rate, adjusted for age, in subjects poisoned by lead in the past who failed to receive specific treatment (P < 0.01). This indicates the possibility of marked, delayed adverse effect of lead on the kidneys in cases when lead body burden has not been reduced by treatment. PMID- 1297309 TI - [Radioactive contamination of cistern waters along the Croatian coast of the Adriatic Sea]. AB - Measurements of radioactive contamination of cistern waters with 90Sr, 134Cs and 137Cs have been carried out along the Croatian coast of the Adriatic Sea. An exponential decline of radioactivity followed the moratorium on nuclear tests. After the nuclear accident at Chernobyl, high radioactivity levels were detected again. The pre-Chernobyl and the post-Chernobyl mean residence times of 90Sr in cistern waters reflect the mechanism by which strontium was released to the atmosphere (atmospheric nuclear weapon tests conducted in the stratosphere or explosions in the Chernobyl nuclear reactor releasing radioactive material to the troposphere). For the pre-Chernobyl period, the mean residence time of 90Sr in cistern waters was similar to that calculated for fallout, being approximately 10 years. The post-Chernobyl 137Cs/90Sr activity ratio has been decreasing, but it has not yet reached the pre-Chernobyl values (approximately 1.6). The time dependent 134Cs/137Cs activity ratio reflects the Chernobyl reactor inventory of these radionuclides. The annual dose for the critical adult population received from 90Sr, 134Cs and 137Cs by consumption of cistern water was estimated to be a few percentages of the dose from natural background radiation. PMID- 1297310 TI - [Monitoring of respiratory symptoms and pulmonary ventilatory function in sisal processing workers]. AB - The prevalence of acute and chronic respiratory symptoms and ventilatory capacity was studied in 50 textile workers exposed to sisal dust. A follow-up study was performed 19 years later and included 20 workers out of the 50. The first study showed a considerably higher prevalence of all chronic respiratory symptoms in the exposed than in control workers although the difference was statistically significant only for chest tightness (P < 0.01). Comparison of the prevalence in the first and the follow-up study in 20 textile workers revealed a statistically significant increase in the rate of chronic cough, dyspnea, chest tightness and nasal catarrh. During the follow-up study the prevalence of almost all chronic respiratory symptoms was significantly higher in exposed than in control workers. Results of ventilatory capacity in 50 sisal workers showed acute reductions of FVC and FEV1 during work shift on Monday and the following Thursday. Comparison of the measured and predicted normal values demonstrated lower values in the follow-up study in comparison to those in the first study. The mean annual fall of ventilatory capacity tests was 0.027 L for FVC and 0.036 L for FEV1. Data suggest that long-term exposure to sisal dust may cause the development of chronic respiratory symptoms and lung function impairment in sensitive subjects. PMID- 1297311 TI - Psychosocial work environment in relation to changes in selected biochemical parameters in district nurses. AB - Sixty-four female district nurses between the ages of 25 and 60 in the greater Stockholm area were subjects in a longitudinal study of psychosocial work environment and biochemical serum parameters. Each participant filled out questionnaires and had blood drawn on four different occasions at three-month intervals during one year. The rating on the fourth occasion showed psychosocial work environment to have deteriorated--social climate and authority over decisions were significantly inferior to those on previous occasions. These changes were accompanied by small but significant elevations of serum cholesterol, calcium and triglycerides. Another pattern was also observed which was probably due to increased health habit awareness--a progressive decrease in glycated haemoglobin and gamma glutamyl transferase. No significant interactions were observed with age or smoking habits--old and young subjects did not differ in their change patterns over time, nor did smokers in respect to non-smokers. PMID- 1297312 TI - Interconvertibility of asbestos fibre count concentrations recorded by three most frequent methods. AB - Simultaneous airborne chrysotile asbestos fibre samples were collected with three types of instruments, namely, the konimeter, the thermal precipitator and the membrane filter, in four asbestos plants (textile manufacturing, asbestos cement production, mining, milling). Linear regression analyses were performed of the membrane filter on the konimeter and thermal precipitator count concentrations, respectively. Sampling was performed at 24-35 locations in each of the processes studied. In order to linearize the relationships and to stabilize the sample variances the data were transformed using the transformation ln(x+1) for both the predictor and the response variables. Eight linear regression equations were developed. The slope coefficients of regressions differed significantly (P < 0.05 or < 0.01) between all the asbestos processes except for the differences of coefficients in mining and milling (P > 0.05). It is concluded that no single conversion factor can be used to reliably convert the konimeter or thermal precipitator to membrane filter asbestos fibre concentrations; a separate conversion factor must be derived for each technological process. In this case the confidence limits of estimates are acceptable for practical occupational hygiene purposes. PMID- 1297313 TI - Animal studies related to Balkan endemic nephropathy. AB - Basic field studies related to the animal population were performed in the region of Slavonski Brod, Republic of Croatia, where Balkan endemic nephropathy is an endemic disease. Pathological changes in several animal species from the locality were examined. The pig population in the area is numerous. Morphologically and physiologically pigs make an excellent animal model for studies of human diseases. Their use in studies should be encouraged, especially because there is a possibility that pigs and humans suffer from the same type of intoxication with a specific xenobiotic of natural origin. According to the mycotoxin theory about the aetiology of Balkan endemic nephropathy, pork meat might be one of the possible hazards for humans. Experiments on laboratory animals provide an excellent possibility to monitor several aspects of pathogenesis and all stages of pathomorphological changes which might then be correlated with Balkan endemic nephropathy. However, the experimental species should be critically chosen because some spontaneous, species-specific lesions of the kidneys are easily mistaken for changes induced experimentally. PMID- 1297314 TI - Tetrahydrobiopterin-dependent formation of endothelium-derived relaxing factor (nitric oxide) in aortic endothelial cells. AB - Inhibition of tetrahydrobiopterin (H4biopterin) biosynthesis in endothelial cells almost completely abolished the agonist-induced formation of endothelium-derived relaxing factor (EDRF) (NO). This inhibitory effect could be antagonized when H4biopterin biosynthesis was restored by activating a salvage pathway. These data indicate that the formation of EDRF strictly depends on the presence of intracellular H4biopterin, which, in addition to Ca2+, may represent a further physiological and/or pathophysiological regulatory of endothelial NO synthases. PMID- 1297315 TI - A functional model of the human cardiac ventricle. AB - A quantitative model is presented which accurately reproduces the time activity curve of the human left ventricular blood pool. Four parameters receive numerical values and may be of clinical value. PMID- 1297316 TI - Assistive technology device use in patients with rheumatic disease: a literature review. AB - Occupational therapists often prescribe assistive technology devices (ATDs) to assist persons with disabilities in performing daily living tasks. Estimates suggest that although most ATDs are used, a substantial proportion are never used or are discarded shortly after they are obtained. A review of the literature on ATDs was carried out to identify factors that contribute to ATD use and disuse. The review focused on persons with osteoarthritis and rheumatoid arthritis, because such persons are frequent users of ATDs. Although the literature review highlighted person-, environment-, and ATD-related factors as relevant to ATD use, it also underscored the dearth of scientific study of the prescription, provision, and use of ATDs. A model is proposed to guide empirical research aimed at identifying non-device users from the outset of treatment so that interventions to improve ATD use may be initiated or alternative interventions implemented. The variables comprising the model pertain to the patient, the patient's living environment, the therapist prescribing the device, and the device itself. PMID- 1297317 TI - A simple confidence interval for the odds ratio in a two-by-two table with one zero cell. PMID- 1297318 TI - [The fourth centenary of Montaigne's death. February 28, 1533-- September 13, 1592. Mysteries of procreation]. AB - During millennia, the mechanisms of procreation have constituted for man an unfathomable and irritating riddle. In the sixteenth century, mystery remained still untouched upon and Montaigne complained about it. The author assigns a place to his communication within the celebrations held this year to commemorate the fourth centenary of the writer's death. In the seventeenth century, De Graaf will establish the identity of ovarian follicles and Van Leeuwenhoek will discover spermatozoons, prominent strides, but their functions will remain mysterious. In the eighteenth century, Spallanzani will demonstrate the semen's fertility, but without linking the former discoveries. In the nineteenth century only, the mechanisms of fertilization will tell their secret, when the necessity of the union of the two gametes, indispensable condition so that the egg can divide by bipartition and give birth to an embryo which will have the double heredity of origin, will be shown up. PMID- 1297319 TI - Induction of peroxisomal beta-oxidation enzymes by dehydroepiandrosterone and its sulfate in primary cultures of rat hepatocytes. AB - Treatment of cultured rat-hepatocytes with 50 microM dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) for up to 5 days resulted in a progressive increase in peroxisomal beta-oxidation and carnitine acetyltransferase activity. After 5 days, the increases in activity were 2.6- and 4.8-fold for peroxisomal beta-oxidation and 11.7- and 17.1-fold for carnitine acetyltransferase over the initial activity, in DHEA- and DHEAS-treated cells, respectively. The stimulation of the activity of these enzymes by the respective agents was dose-related; it was maximum with 50 to 100 microM DHEA and 50 to 250 microM DHEAS, although DHEAS was more effective for stimulation than DHEA. Western blot analyses revealed the induction of acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and carnitine acetyltransferase in the treated cells. Moreover, induction of fatty acid omega-hydroxylase proteins (P-450IVAS) was also revealed. These results indicate that DHEA and DHEAS act directly on hepatocytes. The induction of hepatic peroxisomal beta-oxidation enzymes and several other enzymes in rats administered with DHEA could be accounted for, at least in part, by the direct action of DHEA and its sulfate-conjugate (DHEAS) on liver cells. PMID- 1297320 TI - [Eulogy of Michel Dechaume (1897-1991)]. PMID- 1297321 TI - [Detection of HIV infection in a prison environment]. PMID- 1297322 TI - [Tuberculous abscess of the pancreas]. PMID- 1297323 TI - Monte Carlo simulation studies on the prediction of protein folding types from amino acid composition. AB - In the methodology development for statistical prediction of protein structures, the founders of different methods usually selected different sets of proteins to test their predicted results. Therefore, it is hard to make a fair comparison according to the results they reported. Even if the predictions by different methods are performed for the same set of proteins, there is still such a problem: a method better that the other for one set of proteins would not necessarily remain so when applied to another set of proteins. To tackle this problem, a Monte Carlo simulation method is proposed to establish an objective criterion to measure the accuracy of prediction for the protein folding type. Such an objective accuracy is actually corresponding to the asymptotical limit genereated during the Monte Carlo simulation process. Based on that, it has been found that the average objective accuracy for predicting the all-alpha, all-beta, alpha + beta, and alpha/beta proteins by the least Euclid's distance method (Nakashima, H., K. Nishikawa, and T. Ooi. 1986. J. Biochem. 99:152-162) is 73.0% and that by the least Minkowski's distance method (Chou, P.Y. 1989. Prediction in Protein Structure and the Principles of Protein Conformation. Plenum Press. New York. 549-586) is 70.9%, indicating that the former is better than the latter. However, according to the original reports, the latter claimed a rate of correct prediction with 79.7% but the former with only 70.2%, leading to a completely opposite conclusion. This indicates the necessity of establishing an objective criterion, and a comparison is meaningful only when it is based on the objective criterion. The simulation method and the idea developed here also can be applied to examine any other statistical prediction methods. PMID- 1297324 TI - Mechanisms of meat batter stabilization: a review. AB - Comminuted meat products are a complex mixture of muscle tissue, solubilized proteins, fat, salt, and water. The two theories that have been presented to explain meat batters stabilization are reviewed. The emulsion theory explains stabilization by the formation of a protein film around fat globules, whereas the physical entrapment theory emphasizes the role of the protein matrix in holding the fat in place during chopping and subsequent heating. However, some aspects of stabilization cannot be explained adequately by either one of these theories. In this article the role of meat proteins, aqueous phase, and lipid phase are examined in light of past and recent research findings. PMID- 1297325 TI - Food legumes in human nutrition: a personal perspective. AB - Perhaps with the notable exception, and that only in recent years, of red meat, which contributes dietary saturated fats and cholesterol, two well-known reasons in the etiology of heart-related disorders, no single group of foods has been portrayed in such negative terms as the food legumes traditionally have been during the last 50 years of research in food science and human nutrition. Even more alarming are the trends of continued research on such aspects as the deficiency of sulfur-amino acids (both by amino acid analyses as well as rat feeding studies), and the heat lability/stability of proteinase inhibitors and phytohemagglutinins in various legume species. A survey of literature indicates that over 100 research papers were published during the 1981 to 1990 period alone, in just three journals (Journal of Food Science, Journal of Agriculture and Food Chemistry, and Journal of the Science of Food and Agriculture) having the highest citation ratings in food sciences on these three topics, with a general consensus about the facts that were well established as early as the late 1950s. Considering the proliferation of journals publishing food science and human nutrition related work, especially in the Third World countries, the actual number probably would be much higher. This trend also indicates that we are repeating certain aspects of research on the importance of food legumes in human nutrition. Are we really any closer today in our understanding and appreciation of why the nomadic human made such a choice for their very existence during the transition to a more civilized society? This is a high time to project the image of legumes in human nutrition in proper perspective. The validity of our continued research on certain aspects of legumes in human nutrition, at a time when worldwide the research dollars are becoming increasingly harder to come by, is challenged in this review. Essentially, it is a journey through the author's personal diary that raises several questions in justifying the continued research support for at least some nutrition-related work on legumes and an account of what research areas perhaps need to be targeted in the 21st century. PMID- 1297326 TI - Extrusion of food proteins. AB - Protein extrusion has frustrated earlier predictions regarding its impact in the development of food products. The main reason for this disappointing performance has been its failure to yield fabricated food products with textural quality close enough to that of natural products at competitive prices. Texturized soya protein by extrusion is presently the only commercial success in this area, being incorporated into several convenience products, increasing their protein content and quality and conferring them some desirable sensory properties. Technological and scientific gaps in the extrusion texturization are still to be bridged if this technique is to be applied for upgrading unconventional protein. The precise mechanisms responsible for protein texturization through extrusion are still unclear. Proteins show a very wide range of extrusion behavior that is probably related to large differences in their association properties. New peptide bonds, formed by free amino and carboxylic groups of the protein, were postulated as being responsible for the cross-linking that takes place in protein extrusion. However, disulfide bonds and electrostatic and hydrophobic interactions are regarded presently as the texturization mechanism in this process. The recently suggested suspension (or filled "melt") model for biopolymer extrusion offered a new framework for testing extrusion of novel proteins. According to this view, the large differences between the association properties of proteins produce different types of aggregates. Some of them can be insoluble under extrusion conditions and act as a dispersed phase within the melt phase. The extrusion performance of a protein will thus depend on the amount of insoluble aggregate produced inside the extruder and on protein-protein interactions that occur after the superheated molten mass leaves it. PMID- 1297327 TI - Examination of the DNA sequence-specific binding properties of heat shock transcription factor in Xenopus laevis embryos. AB - The binding of heat shock transcription factor (HSF) to the heat shock element (HSE) is necessary for transcriptional activation of eukaryotic heat shock protein (HSP) genes. The properties of Xenopus embryo HSF were examined by DNA mobility shift analysis employing a synthetic oligonucleotide corresponding to the proximal HSE in the promoter of the Xenopus HSP70B gene. Heat shock induced activation of HSF binding in Xenopus neurulae was not affected by an inhibition of protein synthesis, indicating that the mode of activation may be posttranslational. Also, while HSF binding was activated in control Drosophila cell extracts by in vitro heat shock or other chemical treatments, HSF binding in Xenopus embryo or somatic cell extract was not. Thus, the activation of Xenopus HSE-HSF binding may occur via a different mechanism compared with Drosophila. Furthermore, we determined that the native size of heat-induced HSF in pre- and post-midblastula stage Xenopus embryos is approximately 530 kilodaltons (kDa), which corresponds to a hexamer made up of 88 kDa monomers. Finally, the slower accumulation of HSP70 mRNA to peak levels found at lower heat shock temperatures was not correlated with HSE-HSF binding activity. PMID- 1297328 TI - Molecular analysis of different allelic variants of wild-type human p53. AB - The p53 tumour suppressor gene is intensively studied because mutations in this gene are the most common genetic alteration so far identified in human cancer. Considerable emphasis has thus been placed on characterizing the biological differences between mutant and wild-type p53 protein. This has led to the realization that in cultured cells, mutant p53 behaves like an oncogene, whereas wild-type p53 is a tumor suppressor gene. The p53 protein is also a target for the tumour virus oncogene products SV40 large T, adenovirus E1B, and human papillomavirus type 16 E6, which are all capable of forming complexes to the p53 protein. Although p53 represents an extremely important cellular regulatory molecule which is well conserved, there exists two allelic variants of wild-type human p53 that differ both in primary and confirmational structure. One variant contains an arginine at amino acid 72 (p53Arg), whereas the other form contains a proline at this residue (p53Pro). The possible implications for more than one allelic variant of wild-type human p53 in the general population is unknown. The present study was undertaken to compare some of the biological features of the different wild-type p53 variants. We present data demonstrating that there was a post-transcriptional selection against accumulation of both variants of wild-type human p53 in 3T3-A31 cells, arguing that both forms are proliferation inhibitory in these cells. Both variants of human p53 were stabilized by SV40 large T, but did not displace mouse p53 from SV40 large T. Neither allelic variant of human p53 was able to reduce significantly SV40-mediated anchorage-independent growth of 3T3-A31 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297329 TI - Purification and partial characterization of thiol protease inhibitors from embryos of the brine shrimp Artemia. AB - Thiol protease inhibitor (TPI) proteins in embryos of the brine shrimp Artemia were purified to apparent homogeneity and several of their properties were studied. Four protein fractions containing thiol protease inhibitor activity were obtained by high performance liquid chromatography of Artemia embryo proteins on a C-18 reverse-phase column and these were designated as TPI-1a, -1b, -2, and -3. Acrylamide gel electrophoresis showed that TPI-1a and TPI-1b each consisted of two bands of 11.8 and 13.6 kilodaltons (kDa), while TPI-2 and TPI-3 consisted of only one band of 12.5 kDa. Isoelectric focusing experiments demonstrated that TPI 3 contained one band at pH 5.3, while both TPI-1b and TPI-2 yielded bands at pH 5.2 and 5.3. TPI-1a did not yield any major bands. Amino acid composition analyses of the Artemia TPI proteins showed them to be remarkably similar to one another. All were rich in valine and aspartic and glutamic acids, and devoid of cysteine. Partial trypsin digestion of TPI-1b, TPI-2, and TPI-3 yielded several peptides with identical mobilities on a reverse-phase column and several other peptides with different mobilities, suggesting that the multiple forms of Artemia TPIs may have originated from the same parental protein. N-terminal amino acid sequence analyses of TPI-3 suggest that Artemia TPI proteins are members of the type I cystatin family of protease inhibitors. PMID- 1297330 TI - A novel 49-kilodalton protein from Artemia cross-links microtubules in vitro. AB - A 49 kilodalton (kDa) protein, previously proposed to cross-link microtubules, was purified to apparent homogeneity from cell-free extracts of the brine shrimp Artemia. When incubated with tubulin under assembly conditions, the purified 49 kDa protein cross-linked the resulting microtubules. Preformed microtubules were also cross-linked when incubated with the 49-kDa protein. Upon centrifugation through sucrose cushions the 49-kDa protein cosedimented with microtubules, suggesting a stable association between the cross-linking protein and tubulin. Such microtubules were interconnected by particles which were circular, bilobed, or elongated in shape. Disruption of microtubule cross-linking and dissociation of the 49-kDa protein from microtubules occurred in the presence of ATP and 5' adenylyl-imidodiphosphate (AMP-PNP), a nonhydrolyzable analogue of ATP. The 49 kDa protein was moderately resistant to heat, it did not stimulate tubulin assembly, and it did not react with antibodies to neural microtubule-associated proteins (MAPs) and kinesin. These observations indicate that the 49-kDa protein is different from many known MAPs, a conclusion strengthened by the inability of antibodies raised to the 49-kDa protein to recognize these proteins. The amino terminal 15 amino acid residues of the 49-kDa protein were determined by Edman digestion and an antibody raised to this peptide reacted with the 49-kDa protein on Western blots. Microtubule cross-linking was unaffected by the synthetic amino terminal peptide, even when it was present at a fivefold molar excess over the 49 kDa protein. A search of three protein databanks revealed that the amino terminus of the 49-kDa protein is unique among published sequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297331 TI - Transcription factor activity during cellular aging of human diploid fibroblasts. AB - Human diploid fibroblasts display a limited proliferative life span in vitro, which is directly correlated to the age of the donor from which the cells were explanted. In an effort to identify molecular events that may underlie the loss of proliferative potential in aging fibroblasts, we have determined, at the protein level, the abundance of several cell-cycle-regulated proteins and the activity of the two major members of the activator protein-1 (AP-1) DNA binding complex. We find that cyclin A and p34cdc2 expression is decreased by two- to four-fold in old fibroblasts, but that Fos expression and binding activity are reduced by as much as 95% in old, as opposed to young cells, despite equivalent amounts of p105Rb and Jun proteins being expressed. We have further determined that the composition of the protein complex which binds a consensus (-TGACTCA-) AP-1 site changes dramatically during in vitro aging. Since we have shown previously that AP-1 activity is required for progression through the cell cycle, we propose that the quantitative and qualitative changes seen in AP-1 may play a direct role in the gradual loss of proliferative ability seen as cells approach senescence. PMID- 1297332 TI - Mutational analysis of a DNA sequence involved in linking gene expression to the cell cycle. AB - Entry of budding yeast cells into the mitotic cell cycle requires the activity of a conserved regulatory kinase encoded by the CDC28 gene. The kinase is thought to trigger entry into the cell cycle or START, through association with a number of regulatory subunits known as G1 cyclins. A number of genes whose transcription is dependent on CDC28 and thus linked to START are controlled by two transcription factors, SWI4 and SWI6. The genes controlled by SWI4 and SWI6 include two known G1 cyclins (CLN1 and CLN2), a putative new G1 cyclin (HCS26), and the HO gene whose product initiates cell type switching. SWI4 and SWI6 act through a repeated sequence element, SCB (SWI4,6-dependent cell cycle box), found 2-10 times in the upstream regulatory sequences of target genes. We have constructed a library of mutants in the SCB using doped oligonucleotide mutagenesis. All single base pair changes examined compromised the ability of the SCB to activate transcription in vivo. Analysis of the behaviour of the mutant SCBs in an in vitro DNA binding assay shows that the inability to activate transcription can be explained by reduced binding of SWI4 and SWI6 to the mutant SCBs. This analysis, together with a consideration of the SCBs found upstream of known SWI4,6-dependent genes, leads to the proposal of a revised consensus sequence for this important regulatory element. PMID- 1297333 TI - Regulation of p105wee1 and p34cdc2 during meiosis in Schizosaccharomyces pombe. AB - Temperature-sensitive pat1 mutants of the fission yeast Schizosaccharomyces pombe can be induced to undergo meiosis at the restrictive temperature, irrespective of the mat1 configuration and the nutritional conditions. Using a combination of exit from stationary phase and thermal inactivation of the 52-kilodalton protein kinase that is encoded by the pat1 (also called ran1) gene, highly synchronous meiotic cultures were obtained. Synthesis and tyrosyl phosphorylation of p34cdc2 was evident during meiotic G1 and S phases. During this period there was increased expression of p105wee1, a protein kinase implicated in the tyrosyl phosphorylation of p34cdc2. Following a relatively brief G2 period, during which a reduction in the steady-state level of p105wee1 occurred, there was an approximately 19-fold increase in the histone H1 phosphotransferase activity of p34cdc2. Only a single peak of histone H1 kinase activation was observed, which implies that unlike meiosis in amphibians and echinoderms, p34cdc2 is functional only during one of the meiotic divisions in S. pombe, presumably meiosis II. Stimulation of the kinase activity of p34cdc2 was associated with its tyrosyl dephosphorylation. This is analogous to mitotic M phase and suggests parallels in the mechanism of activation of p34cdc2 during mitosis and one of the meiotic divisions in S. pombe. PMID- 1297334 TI - Factors affecting cellular mosaicism in the expression of a lacZ transgene in two cell stage mouse embryos. AB - In the present study, we have analysed the expression pattern of a lacZ transgene (CMZ12) in preimplantation stage mouse embryos. The transgene is expressed at the two-cell stage, where it shows cellular mosaicism due to variable expressivity. The variable gene expression indicates a partial penetrance of the transgene. The extent of variation in expression is influenced by the genetic background of the oocyte. DBA/2 and CFLP genetic backgrounds promote high expression of the transgene, while Balb/c, C57BL/6, DDK, and F1 (C57BL/6 x CBA) genetic backgrounds give none or very little lacZ activity. In vitro culture of one-cell embryos to the two-cell stage induces the expression of lacZ in all strain backgrounds tested. The variation in CMZ12 expression is a transient phenomenon and does not affect later stage activity of the transgene. Nuclear transfer experiments and DNA methylation analysis suggests that a heritable modification of the transgene locus has not occurred. PMID- 1297335 TI - MSA-35: a protein identified by human autoantibodies that colocalizes with microtubules. AB - We have identified a putative 35-kilodalton protein that colocalizes with microtubules and displays a unique spatial and temporal distribution during the cell cycle of HeLa cells. This protein has been given the designation MSA-35. MSA 35 first appears in association with microtubules and centrosomes of interphase cells exhibiting centrosome separation as a prelude to cell division. This protein is found in conjunction with kinetochore microtubules throughout their appearance. MSA-35 transiently associates with interpolar microtubules following anaphase and the pattern of MSA-35 reactivity in telophase cells suggests that there are at least seven domains within the intercellular bridge. The distribution of MSA-35 during and following recovery from mitotic arrest with nocodazole suggest that it is also present at low levels in interphase cells, can associate with interphase centrosomes, and colocalizes with nascent microtubules. The complex spatial and temporal distribution of MSA-35 indicates that it may be necessary for a series of events in the mitotic process such as the bundling of microtubules. PMID- 1297336 TI - Quantitative analysis of regions of adenovirus E1A products involved in interactions with cellular proteins. AB - Human adenovirus E1A proteins and oncogene products of several other DNA tumour viruses derive much of their oncogenic potential from interactions with cellular polypeptides. E1A proteins form complexes with p105Rb and a related p107 polypeptide, and with at least three other proteins (p60cycA, p130, and p300); all may be required for cell transformation. Using a series of E1A deletion mutants, we have carried out a quantitative analysis of the binding patterns of cellular proteins to E1A products. Binding of most of the proteins was affected at least partially by mutations within the amino terminal 25 residues, amino acids 36-69 within conserved region 1 (CR1), and residues 121-138 in conserved region 2 (CR2). However, the specific binding characteristics of each protein varied considerably. p300 was the only species for which binding was totally eliminated by deletions at the amino terminus. Removal of regions within CR1 eliminated binding of all species except p107 and p60cycA. Deletion of portions of CR2 reduced or eliminated binding of all proteins except p300. Thus, whereas cellular polypeptides generally were found to interact with the same three regions of E1A proteins, specific interactions varied considerably. PMID- 1297337 TI - The distribution of centrosomes in migrating endothelial cells during wound healing in situ. AB - We have examined the distribution of centrioles in rabbit thoracic aortic endothelial cells induced to migrate by wounding the endothelium in situ. Following denudation of the endothelium from a segment of the aorta with a balloon catheter, a wound edge was created from which endothelial cells began to migrate onto the denuded surface. In this in situ model of cell migration, the position of centrioles was determined in cells along the wound edge by immunofluorescence and antibodies which specifically label these cell organelles, and then they were classified in relation to the nucleus and the direction of cell migration as being oriented toward the wound, in the center, or away from wound. At time 0, as in normal unwounded adult rabbit aorta, no preferential orientation of centrioles was evident. Within 12 h after wounding, the centrioles in about 53% of endothelial cells near the wound edge were oriented toward the wound, while in less than 20% of the cells they were oriented away from wound. At 24 h, in cells up to 800 microns from the wound edge, centrioles in only about 10% of the endothelial cells were oriented away from wound, while in about 52% of cells they were found in the center and in 38% of the cells they remained oriented toward the wound. At 48 h, up to 2000 microns from the wound edge, the majority of endothelial cells had their centrioles in the center, possibly as a result of an increase in mitotic index as cells replicate to reestablish an intact endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297338 TI - Functional analysis of the promoter of a sea urchin metallothionein gene. AB - The 5'-flanking region of the metallothionein (MT) gene LpMT1 of the sea urchin Lytechinus pictus includes three copies of a conserved sequence that includes the metal-responsive element (MRE) consensus core sequence required for heavy metal induction of other MT genes, a GC box, a G box of a putative basal level enhancer element which includes another MRE core element, and a poly(C) tract. A fragment of LpMT1 DNA from nucleotides +31 to -309 fused to a chloramphenicol acetyltransferase reporter gene was inducible with cadmium after injection into L. pictus embryos. This induced activity was greatly reduced in a deletion mutant which retained only 195 base pairs of 5'-flanking sequence, including the proximal pair of MREs and the G box, but excluding the poly(C) tract, GC box, and distal MRE. A potent human hMT-IIA gene promoter is marginally functional in L. pictus embryos. In contrast, the LpMT1 promoter is active in HeLa cells and in embryos of the sea urchin Strongylocentrotus purpuratus. The hMT-IIA gene may lack a cis-acting sequence element required for expression of MT genes in L. pictus embryos. The LpMT1 promoter is a powerful, inducible, promiscuous promoter useful for driving the expression of heterologous genes in sea urchin embryos. PMID- 1297339 TI - Cytoskeletal organization following cannabinoid treatment in undifferentiated and differentiated PC12 cells. AB - Confocal microscopy in association with three-dimensional reconstruction was used to examine the changes in the microtubules and microfilaments following cannabinoid treatment of PC12 cells. Microtubules and microfilaments were disrupted in a dose-dependent manner following treatment with 10-30 microM delta 9-tetrahydrocannabinol (THC). A disruption of microtubules and microfilaments was observed following treatment with 30 microM cannabidiol and cannabinol. The amount of microtubules and microfilaments was reduced in a dose-dependent manner following treatment with 10 and 20 microM THC. Cannabidiol and cannabinol reduced the amount of microtubules and microfilaments; however, the reduction was less than that observed with THC treatment. Following the addition of nerve growth factor, differentiated PC12 cells were generally more sensitive to cannabinoid treatments than undifferentiated cells. The possible mechanisms that may account for the changes in microtubules and microfilaments following cannabinoid treatment are discussed. PMID- 1297340 TI - Binding of pp60v-src to membranes: evidence for multiple membrane interactions. AB - Membrane association of pp60v-src, the myristylated transforming protein of Rous sarcoma virus, has been shown to be a receptor-mediated process, which is inhibited by myristylated src peptides containing the N-terminal 11 amino acids of the v-src sequence (MGYsrc). By cross-linking radiolabelled MGYsrc peptide to fibroblast membranes, a 32-kilodalton membrane protein was identified as a candidate src receptor. To elucidate the potential role of p32 in binding pp60v src, we studied the relationship between binding of MGYsrc peptide and pp60v-src polypeptide to cellular membranes. The subcellular membrane distribution of p32 was distinct from that of pp60v-src in transformed cells. Moreover, under certain defined in vitro conditions, it was possible to inhibit peptide cross-linking to p32 without significantly affecting pp60v-src membrane binding. However, when internal sequences were removed from pp60v-src, the binding characteristics of the src deletion polypeptide and MGYsrc peptide became identical. These data indicate that the presence of internal membrane binding domains influences the interaction of myristylated N-terminal src sequences with p32, and suggest that accessory binding factors might be involved in establishing stable contact between pp60v-src and the membrane phospholipid bilayer. PMID- 1297341 TI - The effects of expression of an activated rasG mutation on the differentiation of Dictyostelium. AB - Dictyostelium discoideum contains two ras genes, rasG and rasD, that are expressed during growth and differentiation, respectively. It was shown previously that Dictyostelium transformants expressing an activated rasD gene (a mutation producing a change in amino acid 12 from glycine to threonine) developed abnormally. When developed on filters these transformants formed multitipped aggregates, which did not go on to produce final fruiting bodies, but in a submerged culture assay on a plastic surface they either formed small aggregates or did not aggregate. In this study we transformed cells with the rasG gene, mutated to change amino acid 12 from glycine to threonine. The resulting transformants developed normally on filters, but aggregation under other conditions was impaired. In particular, in submerged culture on a plastic surface they either produced very small aggregates or did not aggregate, one of the phenotypes exhibited by the activated rasD transformants. Molecular analysis of the transformants revealed the presence of high copy numbers of the mutated rasG gene, but the level of expression of the mutant gene never exceeded the level of expression of the endogenous gene. These results indicate a powerful dominant effect of a relatively small amount of the activated RasG protein in Dictyostelium. PMID- 1297342 TI - Zygote giant cell differentiation in Dictyostelium discoideum: biochemical markers of specific stages of sexual development. AB - Sexual development in Dictyostelium discoideum has many unique features making it an attractive eukaryotic model system for the study of biomembrane fusion and intercellular communication. The work presented here provides primary biochemical evidence for two distinct phases during early sexual development that appear to be defined by calcium-dependent gamete cell fusion. In addition, we introduce a novel procedure for the enrichment of zygote giant cells and use this method to define certain wheat-germ agglutinin binding glycoproteins which are specifically located in zygote giant cells and others which are markers for surrounding amoebae in the second phase of development. In addition, a G protein which is present in high amounts early in development is unique to giant cells in the second phase, suggesting a role in phagocytosis. Finally, alkaline phosphatase activity was found to mark the first phase of sexual development, suggesting a role in cell fusion. This contrasts with the patterns of alpha-mannosidase and beta-glucosidase activity that increase late in the second developmental phase, where they likely function in endocyte digestion during the cytophagic period. The developmental significance of these findings is discussed. PMID- 1297343 TI - The fate of female donor blastodermal cells in male chimeric chickens. AB - In previous experiments in our laboratories, chickens that are chimeric in their gamete, melanocyte, and blood cell populations have been produced by injection of dispersed stage X blastodermal donor cells into the subgerminal cavity of stage X recipient embryos. In some experiments, donor cells were transfected with reporter gene constructs prior to injection as a preliminary step in the production of transgenic birds. Chimerism was assessed by test mating, observation of plumage, and DNA fingerprinting. Methods were sought that would provide a relatively rapid analysis of the spatial distribution of descendants of donor cells in chimeras to assess the efficacy of various methods of chimera construction. To date, the sex of donor and recipient embryos was not known and, therefore, numerous mixed sex chimeras must have been constructed by chance, since donor cells were usually collected from several embryos rather than from individual embryos. The presence of female-derived cells was determined by in situ hybridization using a W-chromosome-specific DNA probe, using smears of washed erythrocytes from 16 phenotypically male chimeric chickens ranging in age from 4 days to 42 months posthatching. The proportion of female cells detected in the erythrocyte samples was zero (eight samples) or very low (0.020-0.083%), although 1% of the erythrocytes from a phenotypically male chick that was killed 4 days after hatch were female-derived. The low proportions of female-derived cells were surprising, considering that most of these chimeras had been produced by the injection of cells pooled from several donor embryos and most recipients had been exposed to gamma irradiation prior to injection, thus dramatically enhancing the level of incorporation of donor cells into the resulting chimeras. By contrast, 0-100% of the erythrocytes were female-derived in blood samples taken at 10 days of incubation from the chorioallantois of seven phenotypically normal male embryos that resulted from the injection of blastodermal cells pooled from five embryos into irradiated recipient embryos. Approximately 70% of the erythrocytes in a blood sample from a phenotypically normal female chimeric embryo were female-derived, and 100% of the erythrocytes examined from an intersex embryo bearing a right testis and a left ovary were female-derived. These results indicate that female-derived cells can contribute to the formation of erythropoietic tissue during the early development of what will become a phenotypically male chimeric embryo. It would appear, therefore, that female derived cells are blocked in development or destroyed, or certain male-female combinations of cells may be lethal prior to hatching.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297344 TI - Mutagenesis of Ste18, a putative G gamma subunit in the Saccharomyces cerevisiae pheromone response pathway. AB - The yeast STE18 gene product has sequence and functional similarity to the gamma subunits of G proteins. The cloned STE18 gene was subjected to a saturation mutagenesis using doped oligonucleotides. The populations of mutant genes were screened for two classes of STE18 mutations, those that allowed for increased mating of a strain containing a defective STE4 gene (compensators) and those that inhibited mating even in the presence of a functional STE18 gene (dominant negatives). Three amino acid substitutions that enhanced mating in a specific STE4 (G beta) point mutant background were identified. These compensatory mutations were allele specific and had no detectable phenotype of their own; they may define residues that mediate an association between the G beta and G gamma subunits or in the association of the G beta gamma subunit with other components of the signalling pathway. Several dominant negative mutations were also identified, including two C terminal truncations. These mutant proteins were unable to function in signal transduction by themselves, but they prevented signal transduction mediated by pheromone, as well as the constitutive signalling which is present in cells defective in the GPA1 (G alpha) gene. These mutant proteins may sequester G beta or some other component of the signalling machinery in a nonfunctional complex. PMID- 1297345 TI - Ras modulates commitment and maturation of 10T1/2 fibroblasts to adipocytes. AB - The positive association of the ras oncogene with human cancer and the recognition that malignancy may, in part, represent the imbalance between cell proliferation and differentiation have generated intense interest in the potential role of ras in cell differentiation. We investigated this possibility utilizing as a model system the differentiation of the mesenchymal cell line C3H 10T1/2 (10T1/2) to adipocytes, and a series of transfectants of 10T1/2 cells in which the level of the ras gene product (p21ras; Ras) can be effectively up- or down-modulated. In agreement with previous reports, we found that 10T1/2 cultures, propagated in the resting state for several weeks, spontaneously convert to fat cells at a very low frequency. Downmodulation of endogenous p21ras levels, as a consequence of expression of antisense ras, markedly increased the rapidity and frequency of adipose conversion (6- to 10-fold), which was equivalent in magnitude to that effected by the potent differentiating agent 5 azacytidine. Conversely, overexpression of ras completely inhibited cell differentiation. In addition, adipocytes derived from antisense-ras expressing lines were characterized by a decrease in hormone responsiveness, as well as an apparent deficiency in attaining the terminally differentiated state. These findings suggest that Ras may be a negative regulator of the decision-making step of fibroblast differentiation to adipocytes. In addition, Ras may play an essential positive role in the transduction of hormonal signals necessary for full adipocyte maturation during later progression along the differentiation pathway. PMID- 1297346 TI - Resistance of ADP-ribosylated histones and HMG proteins to proteases. AB - Calf thymus histones (individually isolated or mixtures) and high mobility group proteins were ADP-ribosylated in vitro using [32P]NAD+ and immobilized purified poly(ADP-ribose) polymerase. The modified histones were then subjected to V8 protease or alpha-chymotrypsin digestion and the resulting peptides were separated by electrophoresis on acetic acid-urea-Triton gels. It was found that in vitro ADP-ribosylated histones were much more resistant to proteases than unmodified histones. A similar approach was applied to histones modified by the endogenous poly(ADP-ribose) polymerase in permeabilized NS-1 mouse myeloma cells in culture. In this case, the proteases could not discriminate between modified and unmodified histones and putative mono(ADP-ribosyl)ated peptides appeared in a digestion frame corresponding to that of bulk peptides. These differences are most probably due to the specificity or number of ADP-ribose groups added to the histones by the endogenous or exogenous poly(ADP-ribose) polymerase. Thus, depending on the size of poly(ADP-ribose) attached to nuclear proteins, these modified proteins might display different degrees of resistance to proteolysis. PMID- 1297347 TI - Special issue in commemoration of the 25th anniversary of the founding of the Canadian Society for Cellular and Molecular Biology. PMID- 1297348 TI - The origin of the cancer cell: oncogeny reverses phylogeny. AB - The formulation in 1874 of the biogenetic law by Ernst Haeckel as "ontogeny recapitulates phylogeny" emphasized the structural similarities detected in metazoans between their developmental and ancestral forms. More recently, many workers have independently commented on the similarities observed between the behaviours displayed by dedifferentiated cancer cells and their embryonic precursors. This review will explore a possible linkage between these disparate observations and will suggest that cancer cells behave in ways that are reminiscent of primitive eukaryotic cells. In particular, we suggest that the acquisition of a multicellular level of organization during early metazoan evolution required a critical and difficult change in growth strategy as germ line and somatic cells became distinct. Whereas unicellular free living eukaryotes follow a simple strategy of rapid division as long as conditions permit, the elaboration of powerful growth inhibitory pathways must have been necessary in primitive multicellular organisms to enable some but not all sister cells to stop dividing, even under conditions of nutrient abundance. This limitation on cellular growth would than have permitted the appearance of tissues and organs with differentiated characteristics, ultimately enabling the enhanced survival of the meiotic lineage. Cancer cells might therefore be considered to represent, with their loss of tumor suppressor inhibitory activity and elevation of oncogene stimulatory activity, a reversion to a more primitive evolutionary state capable of indeterminate growth at the expense of the host. By this analogy, the growth phenotypes displayed by cancer cells, embryonic cells, and free-living eukaryotes are fundamentally similar. PMID- 1297349 TI - Towards an understanding of microtubule function and cell organization: an overview. AB - Microtubules exhibit dynamic instability, converting abruptly between assembly and disassembly with continued growth dependent on the presence of a tubulin-GTP cap at the plus end of the organelle. Tubulin, the main structural protein of microtubules, is a heterodimer composed of related polypeptides termed alpha tubulin and beta-tubulin. Most eukaryotic cells possess several isoforms of the alpha- and beta-tubulins, as well as gamma-tubulin, an isoform restricted to the centrosome. The isoforms of tubulin arise either as the products of different genes or by posttranslational processes and their synthesis is subject to regulation. Tubulin isoforms coassemble with one another and isoform composition does not appear to determine whether a microtubule is able to carry out one particular activity or another. However, the posttranslational modification of polymerized tubulin may provide chemical signals which designate microtubules for a certain function. Microtubules interact with proteins called microtubule associated proteins (MAPs) and they can be divided into two groups. The structural MAPs stimulate tubulin assembly, enhance microtubule stability, and influence the spatial distribution of microtubules within cells. The dynamic MAPs take advantage of microtubule polarity and organization to vectorially translocate cellular components. The interactions between microtubules and MAPs contribute to the structural-functional integration that characterizes eukaryotic cells. PMID- 1297350 TI - Intermediate filament proteins: many unanswered questions, few unquestioned answers. AB - Major constituents of the cytoskeleton and the nuclear matrix, cytoplasmic intermediate filament subunits and nuclear lamins belong to a multigene family of proteins whose function is poorly understood. It has now become a general contention that important clues to the physiological roles of these proteins may reside in their developmental and tissue-specific expression patterns, as well as their cellular organization. The present review brings into focus experimental strategies that have been developed, over the past few years, to gain insights into the cellular mechanisms regulating the molecular polymorphism and supramolecular assembly of intermediate filaments. In this context new concepts are discussed that may be pivotal for the orientation of future studies on intermediate filament proteins. PMID- 1297351 TI - Nuclear and chromatin composition of mammalian gametes and early embryos. AB - Changes in nuclear structure and chromatin composition regulate gene activity in many cell types and could play a similar role during early mammalian embryogenesis. Oocytes of the mouse contain the three major lamin species present in somatic cells, although lamin A synthesized by oocytes has a higher molecular mass than the somatic species. Oocyte chromatin contains core histones similar to those of somatic cells, as well as elements that are immunologically related to protamines. In contrast, somatic-type histone H1 is not present. DNA topoisomerase II has not yet been identified in mammalian oocytes, but is abundant in frog oocytes. In contrast to oocytes, sperm do not contain a typical nuclear lamina. DNA topoisomerase II is detectable until late spermiogenesis. Although the DNA of sperm is associated mainly with protamines, some histone may be retained. There is also evidence that the arrangement of the DNA in the nucleus is nonrandom. These results demonstrate differences in nuclear and chromatin composition between oocytes and sperm. After fertilization, the nuclei of cleavage-stage blastomeres undergo programmed modifications. Lamin B is synthesized, whereas lamin A is not. In addition, a set of nuclear proteins is transiently synthesized in mice at the two-cell stage. Changes in embryonic chromatin composition also occur. The relative abundance of transcripts from different core histone genes differs between mouse oocytes and blastocysts. Furthermore, somatic histone H1 becomes detectable beginning at the mid-four-cell stage. As well, during early cleavage stages, expression of plasmid-borne genes becomes dependent on enhancers. Thus, developmentally regulated changes in nuclear and chromatin composition occur during early mammalian embryogenesis, and these may be important for the initiation and regulation of embryonic gene activity. PMID- 1297352 TI - Mechanisms of placental invasion of the uterus and their control. AB - Trophoblast cells of the placenta in many species have acquired mechanisms to invade the uterus, inclusive of its blood vessels, to establish efficient fetomaternal exchange of molecules. This invasion is strictly controlled both spatially and temporally and, in humans, usually continues until midgestation. Key mechanisms underlying various steps in trophoblast invasion are: (i) the attachment to the basement membrane, most likely by binding to laminin; (ii) the detachment from the basement membrane matrix, a process requiring the presence of complex-type oligosaccharides on the cell surface; and (iii) the breakdown of basement membrane components, mediated by secretion of metalloproteases (such as type IV collagenases) and serine proteases (plasminogen activator). Activation of trophoblast-derived metalloproteases appears to be plasmin dependent. Trophoblast invasiveness in situ is controlled by the microenvironment, owing to local production of anti-invasive factors by the decidual tissue of the uterus. One of these factors is TIMP (tissue inhibitor of metalloproteases), which neutralizes metalloproteases in an equimolar ratio. Another is TGF-beta (transforming growth factor-beta), which has a dual effect: it induces TIMP-1 secretion by the trophoblast and decidual cells and promotes differentiation of invasive trophoblast cells into multinucleated giant cells, which are presumably noninvasive. Thus, TGF-beta provides the key control of trophoblast invasiveness in situ. This control is lost in certain choriocarcinomas. In contrast to the response shown by the normal trophoblast, JAR and JEG-3 choriocarcinoma cell invasiveness does not seem to be inhibited by TGF-beta. In fact, in preliminary studies, JAR cells responded to TGF-beta by increased invasiveness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297353 TI - Towards understanding the control of the division cycle in animal cells. AB - The author reviewed the historical process by which classical knowledge of cell division accumulated, to give rise to the molecular biology of the cell cycle, and discussed the perspective of this field of research. The study of the control of cell division began at the turn of the century. It was hypothesized that cell division was a physiological regulation necessary for growing cells to maintain a proper nucleocytoplasmic ratio to survive, which was later substantiated by the finding that amoeba cells could be prevented from dividing by repeated excision of the cytoplasm. However, the observation in Tetrahymena that heat-shocked cells grow exceedingly, but fail to divide, suggested that the cell required the accumulation of a labile "division protein" to initiate division. Mechanisms that control the cell cycle were studied in oocytes by nuclear transplantation and cytoplasmic transfer, and in cultured mammalian cells, protozoa, and Physarum plasmodia by cell fusion. These experiments demonstrated the existence of cytoplasmic factors that control the cell cycle. Maturation promoting factor (MPF) thus discovered in frog oocytes became known to be an ubiquitous cytoplasmic factor that causes the transition from interphase to metaphase in all organisms. The insight into the molecular control of cell growth and division was gained from yeast cell genetics. For biochemical analysis of the cell cycle control, the method to observe the cell cycle in vitro was developed using frog egg extracts. Thus, MPF was identified as a cdc2--cyclin protein complex. Its activity was found to depend on synthesis and phosphorylation of these proteins. However, recently it was found that there were cell cycle phenomena that were difficult to explain in these terms. Various other cellular factors, including nucleocytoplasmic ratio and microtubule assembly, were also found to control MPF, as well as the cell cycle. It remained open to future how these factors control MPF to alter the pattern of the cell cycle. PMID- 1297354 TI - G1 cyclins regulate proliferation of the budding yeast Saccharomyces cerevisiae. AB - The eukaryotic cell cycle is regulated at two points, the G1-S and G2-M boundaries. The molecular basis for these regulatory activities has recently been elucidated, in large part by the use of molecular and genetic analyses using unicellular yeast. The molecular characterization of cell-cycle regulation has revealed striking functional conservation among evolutionarily diverse cell types. For many eukaryotic cells, regulation of cell proliferation occurs primarily in the G1 interval. The G1 regulatory step, termed START, requires the activation of a highly conserved p34 protein kinase by association with a functionally redundant family of proteins, the G1 cyclins. Here we review studies using the genetically tractable budding yeast Saccharomyces cerevisiae, which have provided insight into the role of G1 cyclins in the regulation of START. PMID- 1297356 TI - Calcium storage in nonmuscle tissues: is the retina special? AB - It is now well established that calreticulin is a high capacity Ca(2+)-binding protein which is a major Ca2+ storage protein of the lumen of endoplasmic reticulum membranes in a wide variety of tissues with the exception of skeletal and cardiac muscles. However, in nervous tissue, confusion exists regarding the nature of the intracellular Ca2+ stores, as the organelle responsible for Ca2+ storage has been identified as the endoplasmic reticulum by some investigators and as the specialized organelle, calciosome by others. Calreticulin, calsequestrin, and calsequestrin-like proteins have all been, on different occasions, reported to be present in calciosomes. Cerebral and cerebellar tissues, moreover, have been shown to contain somewhat different systems of Ca(2+)-buffering proteins. In the present paper we discuss evidence that the Ca2+ storage systems of the retina may prove to be more complex than those of other neuronal tissues. Biochemical and immunocytochemical evidence indicates the presence of either an isoform of calreticulin or another protein that is antigenically similar to calreticulin, but of slightly higher molecular weight, in the endoplasmic reticulum of both neurons and Muller glia from rabbit neural retina. However, as retinal neurons express Purkinje cell markers, one may expect to observe the presence of calsequestrin in these cells as well. Secondly, antibodies against the onchocercal RAL-1 antigen recognize a protein sharing 62 65% amino acid sequence identity with calreticulin. The anti-RAL-1 antibodies show specificity for the retina. Whether or not the RAL-1 antigen is an active part of the Ca2+ storage systems of the retina remains to be verified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297355 TI - Regulation of the G2-mitosis transition. AB - The cell cycle is regulated by pathways composed of a dependent series of steps, by timers, and by checkpoint controls which ensure the completion of one event before the initiation of another. This review focuses on the regulation of the initiation of mitosis, with particular emphasis on the regulation of p34cdc2 activity at this point in the cell cycle. The review draws on data from various organisms, but strongly emphasizes the genetic framework as seen in the fission yeast Schizosaccharomyces pombe and the biology and biochemistry of maturation promoting factor in frog oocytes. An attempt is made to include all known genes and proteins where a link can be made to the initiation event. The nutritional size control and its major known controlling elements, the wee1/mik1 protein kinases, and cdc25 protein tyrosine phosphatase are considered in detail along with their regulation. In addition, the checkpoint control pathways which mediate G2 delay in response to failure of DNA replication or DNA damage are examined. PMID- 1297357 TI - Regulation of gene expression in oncogenically transformed cells. AB - Several genes expressed in response to growth factors are also regulated aberrantly in oncogenically transformed cells. The constitutive expression of genes encoding extracellular proteases, transcription factors, and cytokines is often correlated with cell transformation. In several instances, the uncontrolled expression of these genes is the result of transcriptional activation. Therefore, much attention has been devoted to the study of promoter function in transformed cells. We now review the results of recent investigations on transformation dependent gene expression. The activation of several transcription factors in oncogenically-transformed cells is described. Results regarding the regulation of promoters through PRD II/kappa B are presented for cells transformed by a variety of oncogenes. Finally, we discuss the significance of transcription factor activation in the process of cell transformation. PMID- 1297359 TI - [The shape of the nasopharynx in youth: statistical study]. AB - The particular shape of the nasopharynx in the child can influence morphology and physiopathologic behaviour of the mucosa. In such a perspective, it appeared interesting to evaluate the kind and the entity of its variations by means of nuclear magnetic resonance (NMR) in 50 patients (age range: 2 months-16 years). The results show that the nasopharyngeal shape (represented either by bending radius and shape factor) varies in a statistically significant way during the considered age range, while the dimension of the pharyngeal tonsil remains constant in the studied cases. The statistically significant shape variation of the tonsil appears, so, related to its involvement in the shape variation of the whole nasopharynx. PMID- 1297358 TI - Multiple antigens recognized by anti-c-myc antibodies in human cells and Xenopus oocytes. AB - We have investigated the localization, solubility, serum regulation, and phosphorylation of MYC antigens from Colo 320 cells, a human transformed cell line with an amplified c-myc gene, and from Xenopus oocytes, which express high levels of c-myc mRNA. Although MYC proteins are often reported to range from 60 to 68 kilodaltons, our panel of anti-MYC monoclonal antibodies recognized a number of higher and lower molecular mass antigens, in addition to proteins within this range. Based upon various criteria, including cross-recognition by several anti-MYC antibodies, we suggest that some of these antigens are bona fide MYC family proteins. Our results, as well as those of others reported previously, suggest that several MYC antigens may be simultaneously present in cells. The apparent diversity among members of the MYC family of antigens raises the possibility of multiple cellular functions and regulatory roles for these proteins. PMID- 1297361 TI - Parietal neurons encoding visual space in a head-frame of reference. AB - Neurons of the visual system are known to have receptive fields organized in retinotopic coordinates. We wanted to test whether visual neurons existed whose receptive fields were organized in spatial coordinates. Extracellular recordings from single cells were carried out in one area of the posterior parietal cortex (area V6) of a behaving macaque monkey. Among a great majority of retinotopically organized visual cells, neurons whose visual receptive field did not shift with gaze were also found. These cells responded to the visual stimulation of the same spatial position independently of the animal's direction of gaze, that is, their receptive field was anchored to an absolute spatial location. We suggest that these neurons directly encode visual space and are involved in programming visually-guided motor actions in space. PMID- 1297360 TI - [Study of the interaction between plasma proteoglycans and LDL by means of fluorescence spectroscopy]. AB - The relevance of the interaction between LDL and PGs in the development of atherosclerotic processes is well known. However, the exact nature of the interaction and the consequent structural and/or conformational modifications of the lipoprotein remain to be clarified. It has been demonstrated that after this interaction the LDL particle is not recognized by specific cellular receptors and enters the scavenger pathway operating in different cell types. These effects have been shown by using aortic PGs, but PGs are also present in the plasma compartment and may interact constantly with LDL, taking part in the regulation of lipid metabolism. In order to assess the capability of plasma PGs to induce LDL modifications, we investigated their interactions by studying the changes in the organizational parameters of LDL by fluorescence spectroscopy. Plasma PGs were isolated by DEAE Sephacel ion exchange chromatography and Sephacryl S300 gel filtration in two different families: a low-charge PG and a high-charge PG. Human LDL was prepared from plasma of normolipemic donors by ultracentrifugal flotation between 1.025-1.045 g/ml. Steady-state anisotropy measures were obtained by analyzing the rotational diffusion rate of DPH after incubation of LDL with plasma PGs in a physiological ratio. In our experimental conditions, LDL incubation with plasma low-charge PG did not modify DPH fluorescence anisotropy, whereas LDL treatment with highly charged PGs induced a marked decrease of this parameter, suggesting a significant effect on LDL microviscosity. The data show that both the charge and the GAG composition of PGs appear to be critical factors in LDL-PG interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297362 TI - Presence of antisperm antibodies in the serum of Sardinian adult people. II. Study on a selected infertile population in north Sardinia. AB - Among many possible causes of infertility an immunological factor must be considered, in particular the presence of antibodies to spermatozoa in the serum. In previous researches we confirmed the presence of antisperm antibodies in the serum of healthy men of North Sardinia in percentage equal to 2.4% of the considered population. The aim of the present study is to evaluate the correlation between the presence of antisperm antibodies and infertility. The presence of antispermatozoal antibodies has been evaluated in the serum of 124 men (aged 25-50) affected by unexplained infertility utilizing the indirect immunofluorescence and ELISA methods. The presence of antisperm antibodies has been found equal to 19.3% of the tested sera. These results show that the incidence of antisperm antibodies is higher in the serum of male partners from infertile couples than in healthy subjects (P < 0.01), also in a relatively segregated and pure population like the one studied. PMID- 1297364 TI - [Microsurgery and laser surgery in conservative operations on the ovary. Experimental research]. AB - In this study we compared two different conservative surgery techniques performed on 12 ovaries of female rabbits: microsurgery and CO2 Laser surgery. After the surgical procedure all the animals were investigated by a Laparotomy to evaluate the post-operative adhesion formation. Histological examinations were performed on 6 ovaries, to evaluate the possible damage to the ovarian parenchyma. We did not find significant differences between the two methods employed, particularly for the adherence formation and the parenchymal thermic damages: no post operative adhesions were detected respectively in 3 ovaries operated on by microsurgery and 5 by laser surgery; slight adhesions were present in 2 ovaries treated with microsurgery and in 3 with laser surgery; 3 ovaries treated with microsurgery and 2 with laser surgery showed moderate adhesions. Only 2 ovaries treated with microsurgery presented severe adhesions. PMID- 1297363 TI - Computerized topographical analysis of functionally homogeneous neuronal sets. AB - A computer-assisted analysis of the spatial distribution of neurons having homogeneous characteristics is described in this paper. The camera lucida drawings of sections of a brain nucleus and the points representing the neurons labeled on the basis of a specific behavior of discharge rates were digitized on a personal computer Amiga 2000 or IBM compatible. Our software provided: a) the computerized, stereotaxically oriented reconstruction of the stored sections and of the plotted neurons; b) the identification within each section of the mass center (MC) of the units sharing a given behavior and of the area where the density of such neurons was maximal (MDA). The routine was tested on the spatial distribution of neuronal responses to serotonin in the lateral vestibular nucleus. PMID- 1297365 TI - Multi-system approach to study mutagenesis induced by chemical carcinogens. AB - To understand molecular mechanisms of the mutation fixation process induced by a mutagen and carcinogen, a multi-system approach is suggested to reduce the probability that the results are biased by the assay used. In this light we described our different approaches to answer basic questions on the mutagenesis induced by the chemical carcinogen 4-Nitroquinoline-1-oxide. We determined mutations at the molecular level in three experimental systems: a) in prokaryotes (ss M13mp19 lacZ'/E. coli F'lacZ delta M15); b) in eukaryotes (i) ss and ds pZ189 supF/CV1-P/E.coli lacZam and (ii) HPRT in CHO cells with different repair capacity. We think this type of approach can be used to study the genetic effects of new cancer drugs for which the molecular mechanisms of action at the molecular level are still not well understood. We think to apply the know-how to study mutational spectra in tumor derived tumor suppressor genes. PMID- 1297367 TI - The primary care team. PMID- 1297366 TI - [Critical ratio: effects of contralateral masking on normal and pathological ears]. AB - In order to evaluate the central interferences on the auditory efficiency, the effect of contralateral masking noise on Critical Ratio (CR) has been studied in 14 normal ears (control group), in 12 ears with cochlear disorders and in 6 with retrocochlear lesion (acoustic neuromas); in all cases the impairment was unilateral, while the other ear was normal. CR values were calculated for 1 KHz pulsed tones (duration 500 ms, rise/fall 25 ms, duty cycle of 50%); the masking noise was a wide band (90-20,000 Hz) delivered at 40 dB SL. The results have demonstrated that in the presence of contralateral masking noise, CRs don't modify both in the normal ears and in those with retrocochlear disorder, whereas they increase, almost always, in ears with cochlear deafness. These results demonstrate that the involvement of central auditory pathways, because of contralateral noise, makes the auditory efficiency worse, only in ears with cochlear dysfunctions; this behaviour seems to confirm the peripheral origin of CR. PMID- 1297368 TI - Undergraduate medical education: the challenge of change. PMID- 1297369 TI - Diagnosis and treatment of asthma in children: usefulness of a review of medical records. AB - In order to tackle the problems of underdiagnosis and undertreatment of asthma in childhood general practitioners need to be aware of which children in their practices have or might have asthma. In an effort to identify a cohort of asthmatic or potentially asthmatic children a trained audit facilitator studied all the medical records of children aged between one year and 15 years who were registered with 12 Tayside general practices. From a total of 10,685 medical records the frequency of 'key items' sometimes associated with asthma were as follows: one or more episodes of bronchospasm or wheeze 23.7% of children, persistent cough 23.2%, treatment with anti-asthma therapy in the past 20.0%, exercise induced cough or wheeze 5.2% and history of 'wheezy bronchitis' 4.6%. However, in only 896 children (8.4%) had a formal diagnosis of asthma been made. Of all the children, 5.4% had received a prescription for anti-asthma medication within the past three months. Only 1.2% were taking an inhaled corticosteroid and 1.0% sodium cromoglycate, but many more were taking inhaled bronchodilators (3.1%) and oral bronchodilators (1.7%). The findings suggest that a systematic review of medical records by a trained facilitator can identify those children who could benefit from clinical review. Practices who wish to know which of their children have or might have asthma should consider using medical record review to search for key items associated with asthma. PMID- 1297370 TI - Schoolteachers' perceptions and knowledge of asthma in primary schoolchildren. AB - Schoolteachers are known to be concerned about asthma in their pupils but their opinions about the best method of addressing this concern have not previously been investigated. Eleven headteachers and 76 class teachers from 11 primary schools in the Southampton area--eight from the state sector and three private day schools--completed questionnaires. These inquired about the organization of care for asthmatic pupils, the teachers' knowledge, concerns and training regarding the disease, and their perceptions of the need for and source of further education for teachers about asthma. All 10 National Health Service school health services in the Wessex region and 16 teacher training colleges responded to questions about their provision of such education for teachers. The results demonstrated that asthma care in the 11 schools was generally disorganized, with the responsibility for keeping and administering inhalers falling on the school secretary in seven of the schools. All but two of the 11 headteachers and 89% of the class teachers were concerned about asthma, primarily in managing emergencies. Levels of knowledge were low, particularly regarding exercise, and education about asthma was almost non-existent. The great majority of class teachers (86%) wanted more information about asthma and most (67%) looked to the school health services to provide this. None of the school health services in Wessex and only one teacher training college had any planned education about asthma for teachers. Clearly, schools need to receive more information about asthma, both to enable them to cope more ably with their asthmatic pupils and to allay the anxieties of teachers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297371 TI - How effective is systematic care of diabetic patients? A study in one general practice. AB - A method of systematic diabetic care compatible with personal lists, the 'diabetic day', was introduced into a seven partner inner city general practice. The effect on glycosylated haemoglobin levels and the recording of six process measures (fundoscopy, visual acuity, weight, blood glucose levels, glycosylated haemoglobin levels and blood pressure) was assessed. Of the 111 known registered diabetic patients, 64 entered the diabetic day and fulfilled the eligibility criteria. General practice records were analysed retrospectively over a period of four years--the two years before entry into the diabetic day were compared with the subsequent two years. Mean glycosylated haemoglobin levels fell from 10.52% in the year before entry to the diabetic day to 9.71% in the second year after entry (P < 0.01, 95% confidence intervals 0.19 to 1.39). There was a significant increase in all process measures recorded in the general practice notes after entry into the diabetic day. The introduction of systematic care for diabetic patients led to an improvement in recorded process measures and a reduction in patients' glycosylated haemoglobin levels in a general practice which had made previous efforts to improve diabetic care and was already well staffed, organized and motivated. PMID- 1297372 TI - What do medical students seek to learn from general practice? A study of personal learning objectives. AB - With the aim of stimulating learning which is more self directed, fourth year medical students in Liverpool are encouraged to set personal learning objectives for the general practice attachment. On average, a student defines seven objectives for the three week attachment. A classification of objectives derived from the 1989 cohort of students is presented and the objectives could be seen as focusing on the practice population and its health problems, the role of the general practitioner, the work of general practice, the management of general practice, general practice as a career, and general learning. The validity and reliability of the classification are considered. Along with the advantages of this approach in motivating students to learn, the findings are considered in relation to impending changes in undergraduate medical education and the future role of general practice teaching by departments and by practice based colleagues. PMID- 1297373 TI - Practice organization before and after the new contract: a survey of general practices in Sheffield. AB - In order to assess the effects of the new contract on practice organization, all general practices in Sheffield were surveyed just before the new contract came into effect in April 1990, and again one year later. Of the 120 practices, 57% responded in 1990 and 61% in 1991, with 47% responding in both years. There were significant increases in the mean number of clinics and employed staff for the practices responding to both questionnaires and in the proportion of these practices which had a computer. These changes represent a response to the incentives and stated aims of the new contract. PMID- 1297374 TI - Preventable deaths: 16 year study of consecutive deaths in a village in Israel. AB - The aims of this study were to examine mortality in one village in Israel and to determine which deaths could have been prevented by identifying those which were associated with avoidable factors or were caused by conditions which would have been amenable to preventive measures. The medical records of all 171 patients (91 males and 80 females) who died in the geographically defined population of 1800 during the 16 year period 1974-89 were reviewed. The mortality rate, adjusted for age, in the second eight year period (1982-89), was significantly lower for females (4.0 deaths per 1000 females per year) than for males (8.5) (P < 0.01). Downward trends in the birth rate, stillbirth rate and perinatal mortality rate were found, while there was an upward trend in both mean and median age at death. Of the 171 deaths, 36 (21%) were classified as being associated with a total of 44 factors which could be perceived as being avoidable. Twenty five of the avoidable factors were patient related and of these 17 were smoking (more than 20 cigarettes a day in patients aged less than 70 years who died of a smoking related disease). These findings confirm the need for continuous health education for patients. An audit of mortality in general practice is valuable and may contribute towards the prevention of some deaths. PMID- 1297375 TI - General practitioners and emergency treatment for patients with suspected myocardial infarction: last chance for excellence? AB - Pre-hospital coronary care usually consists of a medically staffed coronary care ambulance going into the community from a hospital base, as pioneered in Northern Ireland. In today's medicopolitical and economic climate, this model is not viable in mainland United Kingdom. Current proposals seem to favour a 'scoop and run' policy for heart attack victims, that utilizes the ambulance service but bypasses the general practitioner. Since the majority of telephone calls from people with suspected myocardial infarction are directed to general practitioners, a preferable alternative would be a 'stay and stabilize' strategy that uses the existing referral pattern and builds on general practitioners' medical education and skills. The role of the general practitioner in the management of patients with suspected myocardial infarction is discussed. PMID- 1297376 TI - Night visits. PMID- 1297377 TI - Unrecognized ovarian failure after hysterectomy. PMID- 1297378 TI - Abnormal cervical cytology. PMID- 1297379 TI - Abnormal cervical cytology. PMID- 1297380 TI - Styes: a curious chain. PMID- 1297381 TI - Most physicians still view hospices cautiously. PMID- 1297382 TI - Complications in pain management. PMID- 1297383 TI - The hospice advantage. PMID- 1297384 TI - Drug therapy for cancer pain. PMID- 1297385 TI - Symptom control in patients with advanced cancer. PMID- 1297386 TI - Behavioral approaches in pediatric patients. PMID- 1297387 TI - Bone pain. PMID- 1297388 TI - What is the role of the hospice physician? PMID- 1297389 TI - Non-pharmacologic measures for controlling oncologic pain. PMID- 1297390 TI - The Academy of Hospice Physicians--an appeal. PMID- 1297391 TI - [The fracture risk in the elderly subject: the determining factors]. AB - Recent advancements in the field of bone mass measurements allow us a precise determination of bone mineral density values in various skeletal sites. At present, their determination gives the most valuable information on individual fracture risk. However, we sometimes to witness fragility fractures in presence of regular values of bone mineral density which suggest a satisfactory status of skeletal mineralization. These cases underline that the mechanical incompetence of the skeleton is not simply the result of a decrease in bone mineral density and that other factors are responsible for the increase of fracture incidence in the elderly. In this paper, several factors potentially involved in the occurrence of fragility fractures in elderly people have been considered on the basis of the most recent data of the current literature in this field. These factors, subdivided in bone tissue extrinsic and bone tissue intrinsic factors, include: muscle synergisms, reflex reactions and sensory status, soft tissue features, bone tissue features, structural properties and loading modalities in relation to structural orientation. Awareness and analysis on these factors are important for better management of preventive as well as therapeutic measures for fragility fractures in elderly. PMID- 1297392 TI - [Treatment experience with chronic spinal pain in involutional osteoporosis]. AB - The back pain syndrome which accompanies involutional osteoporosis presents a marked heterogeneity. Acute pain may be due to vertebral fractures, whereas chronic pain may eventually accompany established osteoporosis in which clinical and instrumental evidence are present. Back pain is the consequence of the mechanical (internal or external pressure) or chemical stimulation of pain receptors present in bone tissue, along the vessels, in cartilage, joints, disk, ligaments, and also in soft tissue and muscle (with secondary antalgic contracture). The compression of spinal nerves may contribute to the pain as well. An evident alteration of mood is usually present and represents an important element in the syndrome. This phenomenon interferes with the evolution of pain, in particular as regards its intensity. Besides scales for the evaluation of pain and inability, it is possible to check objective data by means of particular algometers (not easy to employ) or by electromyographic measurements of antalgic secondary contracture of spinal muscle. Gait examination (basography) of patients with painful hip prosthesis may provide objective evaluation regarding specific antalgic activity on bone of drugs. Usually the effective drugs for osteoporosis possess antalgic properties as well, with different mechanisms of action. Three drugs with evident activity are taken into consideration: calcitonin, ipriflavon, aminobutane-bisphosphonate (alendronate). Though each of them possesses some particular activity, the main mechanism of action is dependent on their effect on the local microenvironment, particularly at the level of bone tissue (calcium, cytokine and prostaglandin local concentration), on the modulation of osteoclast activity. In particular alendronate (intermittently administered intravenously) exerts the most evident antalgic activity. Subjective chronic back pain relief is accompanied by (secondary) reduction of antalgic contracture at vertebral muscle level. The activity of the substance against the painful hip prosthesis (documented by basographic gait recording) leads us to conclude that the substance really exerts a direct antalgic action at the level of bone tissue. PMID- 1297393 TI - [Therapeutic strategies in osteoporosis: whom and when to treat]. AB - Postmenopausal bone loss can be efficiently prevented by compounds which inhibit bone resorption, but they can not induce a sustained and relevant bone gain. The initial increase in bone volume observed within the first year of treatment is due to a transient uncoupling between bone resorption and formation: the first is suddenly blocked whereas bone formation decreases slowly within several months; bone is gained until the previously resorbed cavities are refilled. This net increase in bone mass is completely lost as soon as treatment is withdrawn. Since these antiresorptive agents can only be used in order to prevent bone loss, they should be given for several years. Thus, the choice of the drug is also conditioned by its cost and long-term compliance. Estrogen replacement is very convenient, from these points of view in most patients immediately after the menopause. Afterwards, parenteral calcitonin has been, up to now, the sole available alternative with convincing evidence of effectiveness, at least in the medium term. Its cost and the scarce compliance to injections have strongly limited its extensive use. There is increasing evidence that oral bisphosphonates are very effective and therefore they might represent, in the near future, an effective and convenient alternative to estrogen replacement therapy. PMID- 1297394 TI - Clinical trials with bisphosphonates. AB - Bisphosphonates are nonbiodegradable pyrophosphate analogs that are capable of inhibiting bone resorption in vivo and in vitro. For this reason they have been used as effective therapeutic agents in several conditions characterized by increased bone turnover, including Paget's disease, hypercalcemia of malignancy, and metastatic bone disease. More recently, bisphosphonates have been proposed for the treatment and prevention of bone loss in several forms of osteoporosis. Etidronate, the first bisphosphonate to be used in clinical trials, has been found to increase vertebral bone mineral mass in osteoporotic patients. However, the gain in bone mass reaches a plateau after 1-2 years of treatment, with no further increase thereafter. No positive effect on osteoporotic fracture rate has been clearly demonstrated. Moreover, etidronate has been shown to impair bone formation and mineralization at therapeutic doses. Newer, more potent bisphosphonates selectively inhibit bone resorption without impairing bone histology and mechanical strength. Pamidronate has been shown to increase vertebral bone mass in patients with steroid-induced osteoporosis and involutional osteoporosis. In the latter group, this increase did not plateau and was found to be sustained for at least 4 years. However, pamidronate use is associated with relatively poor gastrointestinal tolerability. The use of another agent, clodronate, has been limited by the possible link with the onset of hematologic malignancies. Alendronate is another agent which in studies to date has been found to increase vertebral bone mass in postmenopausal patients. Alendronate also seems to be more potent and better tolerated than pamidronate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297395 TI - The future of osteoporosis diagnosis and therapy. AB - Advancing the diagnosis and treatment of osteoporosis will require progress on several fronts: we must overcome the current widespread failure to fully employ the means already at our disposal for the evaluation, prevention and treatment of osteoporosis. Diagnostic testing must become more effective at characterizing the bone and mineral metabolism of the individual patient. Testing must do far more than identify candidates for treatment; it must permit monitoring of the response to therapy or progression of disease. New therapies should have well characterized, very specific physiological effects. It is critical that they do not produce adverse effects on the bone remodeling mechanism. Gaps in our understanding of the relationships between the mechanical functions of the skeleton and the biology of bone tissue must be filled in order to provide a basis for evaluation and treatment of the skeleton as an integrated organ system. PMID- 1297397 TI - [Hemicrania: primary headache]. AB - Migraine is the commonest form among the so-called primary headaches and the description of its clinical picture is lost in the mists of time. On the contrary, headaches of organic origin have only recently received a proper nosological individuation thanks to the modern technological progress achieved in the field of medicine. The migraine crisis, both with and without aura, is so typical in its clinical features that it does not require subtle instrumental methodologies to be diagnosed. In most cases a careful anamnesis provides all the elements necessary to formulate a precise diagnosis: the positive family history, the time and mode of onset of crises, the nature of head pain, the chronological stages are quite constant whatever the trigger factor may be. Some other considerations add further evidence to the primitivity of migraine. First of all, migraine can be relieved by quite structurally different drugs with different mechanisms of action. In addition, no significant relationship has ever been found between migraine and other pathologies. PMID- 1297396 TI - [Symptomatic headaches in internal medicine: the classification, physiopathological and diagnostic aspects]. AB - Symptomatic or secondary headache occurs when pain itself is a symptom of disease. It is well known that within the general population the percent frequency of secondary headache is lower than that of primary headache. Moreover, some forms do not seem to evidence particular clinical, diagnostic or physiopathological importance. The Authors investigate here a number of clinical aspects of secondary headache, in particular headache in vascular disease (stroke, hypertension, Horton's arteritis). Particular attention is paid to headache in brain neoplasia due to the interest brought about by the diagnostic problems of this disease. Lastly postural headache and its prevalence in the general population is examined. Various physiopathological aspects of this form (stress, psychosocial events) are evaluated. PMID- 1297398 TI - [The pathogenetic bases of hemicrania]. AB - Studies of regional cerebral blood flow in migraine with aura have shown that the aura phase is associated with hypoperfusion in the cortical area which relates topographically to the clinical symptoms. Thus, the previously hypoperfused area becomes hyperperfused. However, there is no strict association between hyperperfusion and headache. The mode of hypoperfusion propagation recalls the circulatory manifestations of experimental cortical spreading depression. In addition, there are no focal cerebral blood flow abnormalities in migraine without aura. During the headache phase of migraine, dilation of both the large extra- and intracranial arteries takes place. A bulk of biochemical evidence has suggested that the pain in migraine is caused by blood vessels which are dilated and sensitized by circulating pain-producing substances e.g. bradykinin, serotonin and histamine (sterile inflammation). Recently, perivascular trigeminal fibres (trigeminovascular system) which, when stimulated, release sensory peptides (substance P and the calcitonin gene-related peptide) capable of provoking marked vasodilation and plasma extravasation (neurogenic inflammation) have been identified. Thus, the activation of the trigeminovascular system is probably involved in the vasodilatative and nociceptive phenomena of the migraine attack. The finding of a reduced endorphinergic brain tonus in migraine patients supports the hypothesis of a central nociceptive derangement in migraine. Nonetheless, the exact relationship between vasodilation and headache remains to be defined. However, the potent antimigraine effectiveness of sumatriptan--an agonist of the serotonin receptors which selectively constricts dilated arteries during the migraine attack--once again stresses the fact that serotonin is probably the crucial factor in the link between vasodilation and headache. PMID- 1297399 TI - [Plasma and tissue antibiotic concentrations: what is their prognostic value?]. AB - Pharmacokinetic studies of antimicrobial agents usually involve the determination of tissue distribution, since most infections develop outside the vascular compartment. Comparative analyses of the results are often complicated by their extreme variability, depending on the various types of methods used, the type of antimicrobial agent, and the characteristics of the various tissue compartments. In general, concentrations in tissue and body fluids with no barriers to penetration of drugs are fairly predictable from blood levels in relation to simple diffusion through capillary pores. This is valid for hydrosoluble drugs such as the beta-lactams as well as liposoluble drugs like the quinolones and most of the macrolides. Thus we may derive, in a predictive sense for the clinical results, both the hematic and interstitial fluid pharmacokinetic profile of the above molecules, which are useful in relation to the MIC or MBC of extracellular pathogens. For molecules such as azithromycin, in which tropism is mainly intracellular, hematic levels do not reflect those which are therapeutic in the infection site. In tissues and body fluids with barriers to the penetration of drugs, such as the central nervous system, eye and bronchial secretions, it is always useful and especially for any new antimicrobial agent to determine the concentrations which are achieved in relation to both dosage and pathological state of the tissue compartment. The significance of the chemotherapeutic formula which gives substantial predictive value of the therapeutic efficacy at the level of blood concentrations in relation to minimal inhibitory concentration of sensitive bacteria, needs to be critically re evaluated in light of the pharmacokinetic behavior of newer antimicrobial agents. PMID- 1297400 TI - [Noci-autonomic-affective automatism, the physiopathological essence of hemicrania. The serotonin theory as a guiding principle in the labyrinth of interpretations]. AB - After thousands of painful long-lasting migraine or extremely violent cluster headache attacks no one has yet traced histological inflammatory or degenerative alterations of the interested tissues able to explain such dreadful pain. Therefore it has seemed logical to include these pains among the unjustified aimless, non finalized types of pain. Furthermore, clinical characteristics of automatism, explosiveness and the course of these pains resemble other aimless pains like those of organic deafferentation (phantom pain) which appear in a desensitized limb after denervation or even in amputated subjects. Intense and long lasting pains in opioid abstinence, mainly located in the chest and in the hip, also have all the characteristics of aimless pain. Idiopathic cephalic pain, together with deafferentation or opioid-abstinence pain, seems to be due to a dysafferentation which, through different channels, follows an analogous mechanism. This mechanism seems to be due to a deficit of autoanalgesia which in both organic deafferentation (phantom limb) and in opioid-abstinence can be related to the disuse of afferences' modulation. In idiopathic headache such a failure of autoanalgesia is likely to be due to a genetic, idiopathic mechanism. Headaches are characterized by a clear deficiency of autoanalgesia which may manifest itself not only at the level of the cephalic segment, which is so rich in afferences, but it may even involve the whole body. Even if pain is the compulsory phenomenon to diagnose headache, one must consider that migraine is a symptomatic triad in which vegetative and emotional phenomena also emerge. These phenomena are interindependent and not interdependent as each of them may appear as a first manifestation of an attack; one must therefore consider the possibility of a "unicum movens". Serotonin was taken into consideration because of its action which interests all or nearly all vegetative-emotional pain transmitting pathways. Today's identification of four types and various sub-types of 5-HT receptors has revealed the extraordinary eclecticism of this transmitter which within migraine's clinical expression underscores that migraine sufferers are characterized by a marked sensitivity to all the drugs capable of acutely or chronically interacting with serotonin metabolism and binding with many serotonin receptor types and sub-types. So even if the migraine sphinx still proposes its enigma, researchers--with their incurable curiosity--may not only find more and more accurate and effective medication for many human beings but also start penetrating a mystery, a great challenge to human imagination. PMID- 1297401 TI - [The etiology of bacterial respiratory infections in adulthood]. AB - Upper and lower respiratory tract infections are the most frequently reported pathologies both in children and in adults. In particular, the most common clinical pictures are otitis media, principally chronic, and acute and chronic sinusitis. The microbiology of otitis media, which has been investigated thoroughly in the last year, confirmed a bacterial origin in 90% of the cases (while the incidence of the viral form is low). The etiologic agents responsible for chronic infections are Gram-negative bacteria, staphylococci and anaerobic bacteria, while in the acute forms, which are rare in adults but frequent in children, the responsible pathogens are principally Haemophilus influenzae, Streptococcus pyogenes and Branhamella catarrhalis. Among the etiologic agents of chronic sinusitis, which, from a clinical point of view, is the most frequently observed, there are staphylococci, Streptococcus pyogenes and many anaerobic bacteria. As regards lower respiratory tract infections, chronic bronchitis is the most frequent pathology in adults. But, in this case, the etiologic agents are more difficult to identify. Analysing the above-mentioned clinical pictures and their relevant etiologic agents, among the different therapeutic proposals, one of the most innovative and recent is represented by azithromycin. Azithromycin is the first of a new class of macrolides termed "Azalides" which shows particular microbiological and pharmacokinetic characteristics. As compared to other macrolides, it has an higher distribution volume, a longer half-life, a deeper intracellular penetration and a wider spectrum of action. It is rapidly concentrated in leukocytes PMN, monocytes, macrophages and fibroblasts and slowly released by these cells to the infected tissues. Azithromycin concentrations in tissues and sites of infection can be increased by the phagocyte uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297402 TI - [The clinical problems of bacterial infections of the upper respiratory tract]. AB - ORL inflammations present particular pathogenetic and clinical characteristics due to the close anatomic and physiological connection among them and to their particular anatomic characteristics. The ear communicates with the rhinopharynx through the Eustachian tube, and this relationship explains how bacterial infections of the upper respiratory tract can cause otitis and how tubal dysfunctions are often responsible for chronic ORL infections, also favoured by the microcavity structure of the middle ear and the mastoid bone. Also the macro- and microcavity anatomic structure of the paranasal sinuses favours chronic infectious diseases, and their adjacency with the endocranial and facial structures justifies the secondary complications of these infections. The palatine tonsil and other structures of the Waldeyer's lymphatic ring play an important immune role in the first respiratory and digestive tract, and infections occurring in these structures (for example, streptococcal infection) can cause pathologies such as rheumatic disease. Other ORL infections are connected to immunodeficiency or atopy. PMID- 1297403 TI - [Antibiotic therapy in bronchopulmonary infections]. AB - Because of difficulties in accurately determining an etiologic diagnosis, the ideal treatment for lower respiratory tract infections remains questionable. Suggested regimens are made on the basis of clinical and epidemiological data. However, the single most common pathogen responsible for pneumonia remains Streptococcus pneumoniae. Atypical pneumonia in younger patients is best treated with macrolides. Older patients without debility or immunodepression are best treated with amoxycillin-ampicillin, second generation cephalosporins or cotrimoxazole, on the basis of local susceptibility patterns of microorganisms. In the treatment of acute bacterial bronchitis in chronic bronchial disease, most antimicrobial agents with activity in vitro against Haemophilus influenzae and Streptococcus pneumoniae are clinically efficacious. Among new pathogens, the importance of Chlamydia pneumoniae is variable according to the studies, and Moraxella catarrhalis was considered almost exclusively responsible for purulent exacerbations of chronic bronchitis. Therapy for empiric treatment of nosocomial pneumonia must ensure coverage for aerobic Gram negative bacilli: the most frequently used includes a semisynthetic penicillin plus an aminoglycoside, but monotherapy with newer broad-spectrum antibiotics (imipenem, ceftazidime, ciprofloxacin, timentin, etc.) seems to be equivalent to combination regimens. The lung is the most common target organ for infectious complications in immunocompromised patients but the diagnostic methods employed in the traditional work-up of pneumonia are often of little or no use in this setting. By far the two most useful clues to management of pneumonia in the immunocompromised host are the underlying host defect and the radiographic pattern of the lung infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297404 TI - [Hypertension and cardiovascular damage]. AB - All major randomized trials of antihypertensive therapy have used cardiovascular events as endpoints. This approach has provided important information, but has also led to a few inappropriate conclusions. In particular, no sound information is available on the ability of antihypertensive therapy to prevent the cardiovascular lesions upon which events are superimposed. However, particularly in mild to moderate hypertensives, the primary goal of therapy is prevention of cardiovascular lesions rather than prevention of premature death. Sensitive and quantitatively reliable methods for evaluation of organ damage in hypertension are now available. For instance, the quantitative evaluation of coronary plaques has recently been employed in therapeutic trials of coronary artery disease; non invasive methods (such as quantitative ultrasonography of carotid artery walls) can be employed in large trials of antihypertensive therapy to answer the question whether some class of antihypertensive drugs, such as calcium antagonists) may be more effective in prevention and/or regression of atherosclerotic plaques than traditional antihypertensive agents. PMID- 1297405 TI - Murine Lyme borreliosis: route of inoculation determines immune response and infectivity. AB - Outer surface protein A OspA is the major outer surface protein of B. burgdorferi, the causative agent of Lyme disease, and has been advocated as a vaccine candidate. It is recognized late or not at all in the course of human Lyme disease, but has been identified as a major antigenic epitope for the anti spirochetal immune response in a number of experimental models of B. burgdorferi infection. We injected B.burgdorferi into mice and tested the appearance of immunoreactivity to OspA by Western blotting. Three routes of infection were studied; other variables investigated were inoculum size and isolate of spirochete and strain of mouse. OspA immunoreactivity, as determined by Western blotting, was readily elicited by injection of sonicates under almost any condition. Intraperitoneal or intravenous injection of infectious spirochetes, especially at infective inoculum sizes, or injection of the noninfectious B31 isolate by any route, resulted in OspA immunoreactivity. However, mice from the three strains tested infected intradermally did not develop significant OspA immunoreactivity, but instead developed strong responses to B.burgdorferi proteins of different molecular weights. These data suggest that during infection within the skin after intradermal inoculation, the OspA protein may be altered in some way to make it less immunogenic than when it is presented to the immune system under other circumstances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297406 TI - Studies on the minimum requirements for in vitro "cure" of tumor cells by cytotoxic T lymphocytes. AB - DBA/2-derived P815 tumor cells form progressively growing tumors when injected into the anterior chamber (AC) of normal BALB/c eyes. By contrast, P815 cells injected into the subconjunctival (SCon) space of BALB/c mice are promptly rejected. Despite these very different outcomes, both AC and SCon tumors elicit an equal clonal expansion of tumor-specific precursor cytotoxic T cells (pTc) within the draining cervical lymph nodes. Moreover, tumor-specific pTc migrate systemically and infiltrate both AC and SCon tumor-containing eyes. The present study explores the hypothesis that pTc generated in response to AC P815 tumors are less efficient "killers" than their SCon counterparts. To address this issue pTc were restimulated in vitro in the presence of exogenous lymphokines to initiate the terminal differentiation of pTc into fully functional cytotoxic T cells (Tc). Then an assay was developed to evaluate the capacity of AC and SCon CD8+ Tc to eliminate P815 tumor cells growing in vitro, i.e., achieve a "cure." This assay established the day tumor cells were completely eliminated (cure), as well as the rate of tumor cell removal. Using this approach it has been learned that pTc harvested from AC and SCon tumor-bearing mice have the same potential for eliminating P815 tumor cells in vitro. Moreover, the efficiency of achieving an in vitro tumor "cure" was found to be remarkably enhanced if exogenous lymphokines, as a surrogate source of T cell "help," were included in the cultures at the time effector lymphocytes were added to the proliferating tumor target cells. This latter finding emphasizes the need for sustained availability of helper factors in order to maximize the efficiency with which Tc can eliminate tumor cells. We interpret the results to mean that successful rejection of tumors in vivo is likely to turn upon (a) arrival of tumor-specific pTc at the tumor site, (b) delivery of "help" that promotes the terminal conversion of these cells into Tc, and (c) sustained presence of "help" which promotes the efficiency of immune elimination of tumor cells. Since equally large numbers of P815-specific pTc enter AC and SCon tumor sites in BALB/c mice, the failure of rejection in the former may be due to an inability of the host to provide immediate and sustained local T cell help. Implications of these studies for the development of immunotherapies for intraocular tumors are discussed. PMID- 1297407 TI - Regional dichotomy of idiotypic expression on senescent B lymphocytes in systemic and mucosal immune systems: selective changes in NPb and T15 idiotypes with aging. AB - The age-associated changes in the expression of NPb and T15 idiotypes on antibody secreting B cells in the spleen and bronchial lymph nodes (BLN) of mice following peritoneal immunization with (4-hydroxy-3-nitrophenylacetyl) acetic acid (NP) and phosphorylcholine (PC) as antigens were investigated. Changes in the NPb or T15 idiotype expressions were detected by the inhibition of anti-NP or anti-PC elispot-forming cells (SFC) with monoclonal (Mab) anti-idiotypic antibodies, Mabs Ac38 and Ac146, or AB1-2, respectively. We found that Mabs Ac38 and Ac146 significantly inhibited anti-NP IgM and IgG SFC responses in the spleen from 4 month old animals in a dose-dependent manner as opposed to a lack of effect on 24 month old splenic cells. There were no significant effects on anti-NP SFC responses in the BLN from either young or old mice. Similar results were obtained using Mab AB1-2 inhibition of T15 idiotype on anti-PC SFC responses in the spleen and BLN. No age-related changes in the gamma- and kappa-light chain contents of the secreted anti-NP antibodies by B cells in the spleen and BLN were observed. The kinetics of the appearance of endogenously auto-anti-idiotype blocked, hapten augmentable (HA) anti-NP IgM SFC responses revealed significantly higher percentages of HA SFC in the spleen and BLN, 14 days after immunization for both young and old mice. The findings suggest that the age-related changes in the idiotypic expression on antigen-specific antibody repertoires in the spleen and mucosa-associated tissues may be caused by the activation of subsets of B cells with different VH gene expressions. PMID- 1297408 TI - Regional differences of B cell immune responses to (4-hydroxy-3 nitrophenylacetyl) acetic acid (NP) antigen in senescent mucosal immune system. AB - The age-associated primary immune response of B cells from the mesenteric lymph nodes (MLN), the bronchial lymph nodes (BLN), lamina propria (LP), Peyer's patches (PP), and the spleen (Sp) of mice following peritoneal or oral immunization with (4-hydroxy-3-nitrophenylacetyl) acetic acid (NP) conjugated bovine gamma-globulin (NP-BGG) was investigated. The induction of immune responses was assessed in 4-, 11-, and 24-month old individual C57BL/6J male mice by determining the number and isotype of anti-NP ELISPOT-forming cells (SFC) in the MLN, BLN, PP, LP, and Sp, and the titer and isotype of serum anti-NP antibody. Data indicated a significant age-associated decline in immunoglobulin M (IgM) and IgG anti-NP SFC in the Sp. No age-related declines were seen in the anti-NP SFC responses in the MLN and BLN. Oral immunization of mice with soluble NP-BGG in combination with cholera toxin resulted in anti-NP SFC responses in LP and PP, which were predominantly of the IgM class followed by IgG and IgA. There were age-associated increases in IgM, IgG, and IgA anti-NP SFC responses in the LP and PP with negligible responses in the SP and MLN. Serum anti-NP IgM and IgG antibody titers in mice immunized intraperitoneally with NP-BGG were found to decline with age. Isoelectric focusing and affinity immunoblotting revealed a loss of several anti-NP antibody clonotypes in the immune serum of old mice following parenteral immunization with NP-BGG as opposed to several new antibody clonotypes following oral immunization. The findings suggested age-related regional differences of B cell immune responses to the NP antigen in the mucosal immune system. These changes in the NP specific antibody repertoires in the spleen and mucosa-associated tissues may be regulated by different mechanisms operating towards different antigens, and this in turn may influence the characteristic antibody responding to these antigens. PMID- 1297409 TI - Persistent pulmonary interstitial fibrosis, induced by immune response to TNP, is associated with altered mRNA procollagen type I:III ratio. AB - Pulmonary interstitial fibrosis is characterized by a progressive increase in connective tissue in the lung parenchyma. Fibrosis is associated with conditions that result as a consequence of cell mediated responses including graft versus host disease, delayed type hypersensitivity reactions, and granulomas. The hapten immune animal model for pulmonary interstitial fibrosis correlates the nonresolving fibrosis observed in the lung parenchyma directly with the animal's prior immunization to the hapten. Because the model is patterned after the well studied contact hypersensitivity assay in the skin, the immune response can be directly correlated with a cell-mediated (T-lymphocyte) immune mechanism. Previously, we reported that hapten-immune animals showed increased collagen deposition as identified on routine paraffin fixed slides that were stained with Masson's trichome. In this report, morphometric procedures were used to quantitate the fibrotic lesion. Fibroblasts were harvested from lungs of all treatment groups, cultured, and assayed for collagen production. Once it was determined that collagen production by fibroblasts was similar to that recorded in assays using fresh lung tissue, the fibroblasts were used as a homogeneous cell source for RNA. Total RNA from various treatment groups was used to assess the ratio of mRNA for procollagen I:III using slot and northern blot hybridization procedures. An increased ratio in the procollagen type I:III mRNA was observed in total RNA isolated from fibroblasts from immune and challenged hamsters, and not in samples from all other groups. These results support the hypothesis that the activated T lymphocytes involved in "contact" hypersensitivity-like reactions in the lung regulate not only the quantity, but also the quality of collagen produced by the fibroblasts in the lungs of the hamsters that develop nonresolving fibrosis. The model may be important for the study of skin and pulmonary disease induced by exposure to environmental haptens. PMID- 1297410 TI - Tonsillar (Waldyer's ring equivalent) lymphoid tissue in the rat: lymphocyte subset binding to high endothelial venules (HEV) and in situ distribution. AB - We have studied lymphocyte traffic to the Waldeyer's ring equivalent (WRE) lymphoid tissue of the rat, by measuring the in vitro binding of various lymphocyte subsets to high endothelial venules (HEV) in the WRE. In addition, we studied the in situ distribution of these lymphocyte subsets. WRE tissue consists of B and T cell areas; the latter contain HEV. B cells outnumber T cells, and T helper (CD4) cells outnumber T suppressor/cytotoxic (CD8) cells (T/B ratio = 0.7; CD4/CD8 ratio = 5.1). In vitro studies of lymphocyte binding showed that lymphocytes adhere almost equally well to HEV in WRE tissue as to HEV in lymph node (LN) tissue, and much better to HEV in WRE than to HEV in Peyer's patch (PP) tissue. T cells bind better than B cells to HEV in WRE (T/B binding ratio = 1.8), and CD8 cells better than CD4 cells (CD8/CD4 ratio of 2.9-3.2, dependent on cell source). The observed preference of T over B cells in binding to HEV is not reflecting the distribution of these lymphocyte sets in situ. In this respect the WRE takes a unique position, since in other lymphoid organs T/B binding ratios parallels T and B cell distribution in situ. This may suggest a much more rapid passage of T cells through the WRE than through other lymphoid tissues, although other mechanisms cannot be ruled out. The CD8/CD4 binding ratio to HEV in WRE contrasts with situ distribution of these cells also; however, this is found for LN and PP lymphoid tissue too.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297411 TI - Suppression of resistance to Giardia muris and cytokine production in a murine model of acquired immune deficiency syndrome. AB - Peyer's patch (PP) T cells through the production of appropriate cytokines foster the development of immunity to the intestinal protozoan parasites such as Giardia. T cell destruction by the human immunodeficiency virus precedes the development of acquired immune deficiency syndrome. Thus, HIV may increase susceptibility to intestinal parasite infections. Therefore, we measured the resistance and T cell cytokine responses to Giardia in C57B1/6 mice infected with the retrovirus LP-BM5 which produces a murine AIDS (MAIDS). Mice with MAIDS and controls were intragastrically challenged with 1 x 10(5) G. muris cysts. Fecal counts were measured weekly following challenge. Also, PP T cell production of interleukin (IL)2, IL3, IL4, and Interferon-gamma in response to G. muris trophozoite antigens displayed on antigen presenting cells were measured at these times. Prior to day 14 of the infection, the number of Giardia cysts in the retrovirus group paralleled that in controls. However, by day 21 after Giardia infection, mice with MAIDS failed to clear the Giardia cysts from the intestine while the control mice were completely free of cysts. IL2 and IL4 production in response to Giardia trophozoites by unfractionated PP lymphocytes were severely depressed in the retrovirus infected group, while IFN-gamma production was increased. Depressed cytokine production was most likely due to depressed PP T cell numbers. When fractionated enriched T cells were adjusted to a uniform concentration in in vitro immunization cultures, the production of IL2 and IL4/IL5 were similar between retrovirus infected compared with control mice. Recoverable PP T cells were lower in mice with MAIDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297412 TI - [Growth and development of Metorchis orientalis in chicks and its adult morphology]. AB - In order to observe the infectivity, growth and development and adult morphology of Metorchis orientalis, a total of 40 chicks were experimentally infected with 100 metacercariae respectively, collected from Pseudorasbora parva. The worms of various developmental stages were recovered from chicks at 1.5, 3, 5, 7, 9, 11, 14 and 21 days after infection, and they were prepared for morphological observations and measurements. All of the worms were found in the gallbladders of chicks, and their recovery rate was 32% in average. The growth of the body was rapid from 9 to 11 days after infection. The genital primordia appeared in 1.5 and 3-day old worms, and ovary and testes were first observed in 5-day old worms. Thereafter, genital organs gradually matured and completed up to 11 days after infection. The adult worm was leaf-like, and possessed a convoluted tubular seminal vesicle, an ovoid ovary, a sac-like seminal receptacle, 2 lobed-testes and follicular vitellaria. Eggs were 31.9 x 15.3 microns in average size, ellipsoid to elliptical in shape and possessed abopercular thickenings. From the above results, it is concluded that M. orientalis grows in sigmoid pattern in chicks, and their genital organs fully mature between days 9 and 11. It is also confirmed that a chick is a new definitive host of M. orientalis. PMID- 1297413 TI - Trematodes of the genus Haematoloechus (Digenea: Plagiorchiidae) from frogs in Korea. AB - Total 242 Rana nigromaculata and 9 R. catesbeiana were collected from the various localities in Korea from February 1989 to July 1991, and their lungs were examined. Five species in genus Haematoloechus, i.e., H. sibiricus japonicus (Yamaguti, 1936), H. nanchangensis Hsiung, 1934, H. variegatus (Rudolphi, 1819), H. lobatus (Seno, 1907), H. lobatus koreanus, were identified in this study. Among them, H. lobatus koreanus was a new subspecies and H. variegatus and H. lobatus were newly recorded from Korea. PMID- 1297414 TI - [Aporocotyle theragrae (Trematoda: Aporocotylidae) from the blood vessel of Theragra chalcogramma]. AB - Two fully matured specimens were collected from the blood vessel of two fish, Theragra chalcogramma, which was bought at the Emun market of Seoul in May, 1985. The blood fluke has no pharynx and suckers. Its body surface was covered with minute spines forming fan-shaped groups, 15 microns long. The intestine was H shaped, and the ratio of esophageal length to body length was 1:6.1-6.8. Irregular shaped testes were 109-114 in number, occupying the intercecal space from cecal bifurcation to the genital pore. The present species was identified as Aporocotyle theragrae. This is the first report of the species in Korea. PMID- 1297415 TI - [Experimental Cryptosporidium parvum infection in a Korean native calf isolated from a Korean mouse]. AB - This study was performed to investigate experimental transmission of Cryptosporidium parvum in a calf. A 25-day-old Korean native calf was inoculated per os with 1 x 10(6) C. parvum oocysts isolated from a Korean mouse. The calf commenced oocyst discharge in feces on post-inoculation day 4, and continued until the day 11. The number of discharged oocysts peaked (4.9 x 10(5)) on post inoculation day 6. However, the calf did not show signs of diarrhea. The present results indicate that C. parvum is cross-transmissible between the calf and the mouse. PMID- 1297416 TI - [Infection status of larval anisakids in Astroconger myriaster collected from the Southern Sea near Pusan]. AB - A study was presented on the anisakid larvae in Astroconger myriaster which were caught at the Southern Sea and saled at Pusan area. The nematodes were morphologically classified into Anisakis sp. and Contracaecum sp. after fixation in 70% ethanol and clearing in lactophenol. Total of 1,768 larval anisakids were collected from 259 (67.8% positive rate) out of 382 examined A. myriaster. Total 642 larvae of Anisakis sp. were obtained from 94 (24.6%) and 1,126 Contracaecum sp. were recovered from 165 (43.1%) fish. The average number of worms per infected fish was 4.6. The infection rate increased according to the length of fish, and all of the fish over 71 cm were found infected. The numbers (proportions) of recovered worms by the organs were 1,440 (80.5%) in the omentum, 166 (9.4%) in the intestine, 107 (6.0%) in the stomach, 32 (1.8%) in the skin, 18 (1.0%) in the muscle, 13 (0.7%) in the liver, and 2 (0.1%) in the head. The larvae in the muscle may infect the humans who are enjoying raw sliced meat of the fish. PMID- 1297417 TI - Experimental infection of pigs and cattle with eggs of Asian Taenia saginata with special reference to its extrahepatic viscerotropism. AB - Asian Taenia saginata, tentatively called Taenia saginata taiwanensis, has been described to be infected in its metacestode stage only in the liver of intermediate host animals. Experimentally, however, we found that the metacestodes of the Asian Taenia saginata are also infected in other viscera than the liver of pigs (Landrace-Duroc-Hampshire) 4 days to 4 months postinoculation (PI). Viscerotropism of cysticercosis was apparent because a majority (70.7%) of the non-calcified cysticerci were found in the livers while a minority were found in extrahepatic organs such as the omentum (19.2%), lungs (8.1%) and serosa of colon (2.0%). When experimentally infected to cattle, Asian T. saginata cysticerci were also observed calcified in the livers. On the other hand, classical Taenia saginata metacestodes infected the muscles and viscera of the Holstein-Friesian cattle whereas no infection was observed in experimental pigs. Extrahepatic metacestodes of Asian T. saginata, which were obtained from an experimental pig were confirmed to be infective to a male volunteer. This extrahepatic viscerotropism of Asian T. saginata metacestodes in experimental pigs explains well the transmission modes of Asian T. saginata among people considering the eating habits. PMID- 1297418 TI - Susceptibility of various animals to Pneumocystis carinii infection. AB - Pneumocystis carinii (Pc) is an important opportunistic pathogen of immune compromised hosts, and is known to infect various animals. The present study observed the infection status of 6 mammals and 3 strains of albino rats with Pc after suppression of their immunity. Methyl-prednisolone was injected once a week and tetracycline was supplied with water for 5 to 21 weeks. Hamsters, guinea pigs, rabbits, dogs, cats and pigs were negative by impression smear, and only the rats were found infected by Pc. All of the three strains of rats, Sprague Dawley(SD), Wistar(W) and Fisher(F), were infected by Pc but W rats showed heavier degree of infection in earlier period than F or SD rats. The present findings suggest that W rat is the best among the animals used in the present study for production of Pc. PMID- 1297419 TI - Transmission modes of Pneumocystis carinii among rats observed by karyotype analysis. AB - To observe the transmission patterns of karyotype of Pneumocystis carinii (Pc) by rat colonies, three strains of rats, Sprague-Dawley(SD), Wistar(W) and Fisher(F) from various animal vendors, were suppressed of their immunity by injection of methyl prednisolone. They were kept for 5 to 13 weeks in 3 different animal rooms, A, B, and C. The purified organisms were prepared in low melting point agarose gel by embedded lysis method for pulsed field gel electrophoresis. Field inversion gel electrophoresis showed 2 patterns of the karyotype of Pc. The rooms A and C contained SD rats from the source P, and also the room A was used for F and W rats. However, Pc from all of the SD and F rats in the room A showed same karyotypes, the pattern I. The SD rats from different vendors, M and S, were reared in the room B, and shared the same Pc karyotypes, the pattern II. The rats of W strain were from the vendor M, and immune-suppressed in the animal room A. Five weeks after the experiment, the Pc showed the karyotype pattern II but the pattern became mixed with the type I after 7 to 8 weeks. The findings revealed that the animals born and reared in the same animal quarter harbored Pc with same karyotypes. If the animals were kept under immune-suppression in the same room with heavily infected hosts, they could be infected by Pc from their neighbors. The present experimental findings suggest that Pc is transmitted among rats through the air. PMID- 1297420 TI - [Immunological approach for classification of free-living amoeba in Korea]. AB - Acanthamoeba spp., free-living amoebae inhabited in moist soil, pond, freshwater, sewage, atmosphere and swimming pool, may be causative protozoa of the fatal primary amoebic meningoencephalitis in experimental animals and humans. In this study, Acanthamoeba spp., including Acanthamoeba sp. YM-4 (isolated strain from Korea) had been compared by the two-dimensional electrophoresis and hybridoma technique as well as the difference of morphological characteristics. Trophozoite of Acanthamoeba sp. YM-4 is usually uninucleate and show the hyaline filamentous projections (acanthopoda). No flagellate stage observed. Cysts have two walls, the outer wall is nearly circular, but inner wall is oval or some irregular. As results of SDS-PAGE for lysate of Acanthamoeba sp. YM-4, 16 major protein fractions are similar to those of A. culbertsoni, but different to A. royreba and A. polyphaga. Findings of two-dimensional electrophoretic patterns of Acanthamoeba sp. YM-4 are almost same to those of A. culbertsoni, The isotype of monoclonal antibodies produced from McAY 6, McAY 7, McAY 8, McAY 13 and McAY 16 clones were IgG1, and McAY 10 and McAY 11 clones were IgM. As results of the cross-reactivity among various amoebae using ELISA with monoclonal antibodies, McAY 7 monoclonal antibody (molecular weight 43 kDa by EITB) was only reacted with Acanthamoeba sp. YM-4, but McAY 6 and McAY 10 monoclonal antibodies were reacted to A. culbertsoni as well as Acanthamoeba sp. YM-4. PMID- 1297421 TI - Measurement of 150 kDa protein of Taenia solium metacestodes by antibody-sandwich ELISA in cerebrospinal fluid of neurocysticercosis patients. AB - An antigenic protein in cystic fluid of Taenia solium metacestodes (CF) of 150 kDa was measured by antibody-sandwich ELISA in serum and cerebrospinal fluid (CSF) of neurocysticercosis patients. Capture antibodies were rabbit antisera against CF (RACF) and a monoclonal antibody (MAb) against 150 kDa protein in CF. Lower limit of antibody-sandwich ELISA was 8 ng/ml of the protein. Except CF, no tested helminths extracts reacted. Levels of the protein in 351 sera from 255 patients (55 surgery confirmed and 202 antibody and CT/MRI confirmed) were below sensitivity of the assay. Of 276 CSF from 212 patients, 31 samples (11.2%) showed positive findings. This assay, therefore, was not sensitive enough to be a diagnostic. Instead, the 150 kDa protein appeared in CSF in such situations as in 2 days after praziquantel treatment, or as in a patient infected with a racemose cysticercus with degenerated cyst wall. Of cases whose follow-up CSF were assayed, 2 cases showed that the protein appeared intermittently. These results suggest strongly that appearance of free 150 kDa protein is associated with cyst wall rupture. In CSF which contained the 150 kDa protein over 61 ng/ml, the protein was recognized in SDS-PAGE before and after immunoprecipitation. PMID- 1297422 TI - [Antigenic localities in the tissues of Metagonimus yokogawai in the period of growth]. AB - In order to observe the antigenic localization in the tissues of Metagonimus yokogawai in growth stages, immunogoldlabeling method was applied to using serum of the cat which infected with isolated metacercariae from Plecoglossus altivelis. The sectioned worm tissues from each growth stages were embedded in Lowicryl HM 20 medium, stained with infected serum IgG and protein A gold complex (particle size: 12 nm) and observed by electron microscopy. In the worm tissues of all experimental groups, the gold particles were specifically concentrated on the tegumental syncytium and cytoplasm of the tegumental cell as well as the secretory granules in the parenchymal tissue. In the 16th and 20th week grown worm tissues, the gold particles were specifically concentrated on the vesicles in the tegumental syncytium and cytoplasm of the tegumental cell. The gold particles were specifically concentrated on the caecal epithelia of the 4th, 8th and 12th week growth groups but slightly concentrated on those of the 16th and 20th week. PMID- 1297423 TI - [Comparative antigen analysis of Trichomonas vaginalis by enzyme-linked immunoelectrotransfer blot technique]. AB - Analysis of six isolates of Trichomonas vaginalis was carried out with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunoelectrotransfer blot (EITB). Trichloroacetic acid-treated antigens of the 6 isolates revealed 25 protein profiles ranging 12-170 kDa of molecular weight in SDS-PAGE. In EITB, the specific immunogenic bands were visualized at 51 kDa and 96 kDa when HY-1 antigen was probed with different mice sera immunized with 6 isolates of T. vaginalis. The banding patterns with different sera showed isolate to-isolate variability. In EITB, homologous antigen (HY-1) did not show any enhanced response in reacting to homologous antiserum (HY-1) when 6 isolates of T. vaginalis were probed with a single serum (HY-1). It is assumed that the different banding patterns of six isolates show isolate-to-isolate variability and immunogenic common bands in 41, 47, 74 and 94 kDa on EITB may connote the important significance on immune response in T. vaginalis infection. PMID- 1297424 TI - Study on vector mites of tsutsugamushi disease in Cheju Island, Korea. AB - Because no reference on trombiculid mites (Acarina: Trombiculidae) in Cheju Island where tsutsugamushi disease is highly endemic had been available, studies on trombiculid mites in Cheju Island were implemented during the period of August 1991-April 1992, and the results obtained are summarized as follows: (1) The species and numbers of the field rodents collected were 143 Apodemus agrarius chejuensis (92.3%), 11 Crocidura lasiura (7.1%) and 1 Micromys minutus (0.6%). From total 12,075 chiggers harvested, 9 species of 4 genera in Trombiculidae were identified. (2) The predominant species through all seasons was L. zetum (43.3%), followed by L. orientale (27.4%) and L. scutellare (26.6%). However, in autumn when the most cases of tsutsugamushi disease occur, L. scutellare was prominently predominant, having 79.8% of the collected chiggers. (3) Among 1,142 L. scutellare examined for Rickettsia tsutsugamushi by means of IFA test, 6 individuals were found positive showing 0.5% of infection rate. This is the first finding that L. scutellare is the second vector species of tsutsugamushi disease in Korea. (4) Antibody positive rate of A. agrarius chejuensis sera were 31.2% (44/139), and 1 M. minutus serum was also found positive. The seropositive rates by season were not so significantly different. PMID- 1297425 TI - Mass treatment of head louse infestation with Sumithrin powder in primary schools in Korea. AB - A mass treatment of head louse infestation with Sumithrin powder (0.4% phenothrin) in primary school children was implemented during the period of September 1991-May 1992. The infestation rate of total 2,515 children was 38.6% in average (21.2% in boys and 57.2% in girls). The reduction rate of head louse infestation was 93.4% with a single treatment and 94.8% with double consecutive treatments with about 10 days interval, which indicated that a single treatment would be recommended for the mass treatment in the community. Long term follow-up after Sumithrin powder application for head louse control in a primary school showed that the infestation rate dropped from 33.1% before treatment to 5.4% by seven months after treatment, giving a 83.4% reduction rate. PMID- 1297426 TI - Telepathology--visual telecommunication in pathology. An introduction. PMID- 1297427 TI - Telemicroscopy. Design considerations for a key tool in telepathology. AB - The paper introduces telemicroscopy as a mean to establish online telepathology services. It is differentiated between specialized point to point connections with only a few restrictions on one side, and telecommunication links available inexpensive worldwide in the form of the public telephone net on the other side with the restriction of a limited channel capacity. The restrictions imposed by the application of the telephone net (preferentially the ISDN service) are discussed and strategies outlined to overcome these restrictions. It is concluded, that if dedicated broadband connections are available, realtime telemicroscopy links can be realized immediately with available equipment. If a switched and general available telemicroscopy service applying public telecommunication links is favoured, for effective and acceptable ("online") links, computer intelligence has to be introduced to allow effective strategies for data reduction and data transmission. In this field design and development efforts are still necessary. PMID- 1297428 TI - Aspects of standardization in telepathology. AB - Effective telepathology is only possible, if the partners are supplied by a broad variety of equipment connected by far-spread communication lines. These prerequisites can only be fulfilled if technical and medical standards are available obligate for all participants. The technical and medical aspects of those standards are described in general and include procedures and notations in pathology, standards of the image source, image sampling, clinical information, classification of diagnosis, communication channels, hard- and software equipment. New standards should only be developed for those not existing, or if the already existing ones are not appropriate. The standardization classes should allow flexible formats and be developed as "open modules" allowing "individual" peripheral work stations and progressive development in the future. PMID- 1297429 TI - Legal aspects of telepathology. AB - The legal aspects of telecommunication are discussed briefly. Telepathology induces no new legal conditions; however, due to its somewhat higher diagnostic error rate specific problems may occur. Both the pathologist and hospital should clarify the internal liability conditions. The pathologist should be aware that he is still liable for errors induced by the technician, even without having the possibility of responsibility or any supervision. PMID- 1297430 TI - Visual telecommunication for expert consultation of intraoperative sections. AB - Histopathological images of intraoperative sections were transferred by use of normal telephone line between the Department of Pathology, Thoraxklinik, Heidelberg, and the Institute of Pathology, Hospital Baumgartnerhohe, Vienna. The images were digitized using a colour TV camera and stored in a specific image transmission system (VP2000). The transfer of one image lasted 1.4-2 min at average; normally two different areas of the section were transmitted. The expert discussion including the clinical history usually started a few minutes prior to the image transfer, and was finished 3 min after the transfer of the last image. A substantial assistance in the intraoperative classification of the disease was achieved in 37% of the 35 submitted cases. The images transfer was only useful for medium to high magnifications of the microscope, i.e., an objective x 25 or higher. The trail allows the following conclusions: a) Visual transfer of microscopic images is a useful technique for expert consultation of intraoperative sections, and can give additional information in 20-40% of the analyzed cases; b) it is useful only for medium or high microscopic magnifications and limited by the spatial resolution of the TV cameras. PMID- 1297431 TI - Human performance studies of the video microscopy component of a dynamic telepathology system. AB - Human performance studies were performed to evaluate the video microscopy component of a proposed dynamic telepathology system. Frozen sections from breast biopsies of 115 patients were evaluated by both conventional light microscopy and video microscopy by 6 pathologists. Receiver operator characteristic (ROC) curve studies showed nearly identical levels of discrimination between benign and malignant breast lesions for both viewing modalities. Viewing times were significantly greater (p < 0.001) for video microscopy but within a time frame that rendered the technology of potential value for pathology diagnostic applications. Large degrees of interobserver viewing time variability were found for light and video microscopy. PMID- 1297432 TI - The validity of frozen section diagnosis based on video-microscopy. AB - To investigate the accuracy of video-microscopy of frozen sections, two pathologists reexamined 80 cases of archival material, on which frozen sections had previously been performed. Diagnoses based on the two trials (Observer 1 and 2) and diagnoses obtained in the original frozen section situation were compared with the final diagnoses based on paraffin embedded material. Observer 1 had two false negative diagnoses, but no false positive, whereas Observer 2 had one false positive, but no false negative diagnosis when compared with the final diagnoses. No false positive or false negative diagnoses were made in the original frozen sections situation and the number of inconclusive diagnoses were 5, as compared with 6 and 8 in the two trials based on video-microscopy. More experience with video-microscopy will probably achieve a quality of frozen section diagnoses similar to that of direct light-microscopy. PMID- 1297433 TI - Frozen section service via the telenetwork in northern Norway. AB - We present preliminary results of remote frozen section service for two local hospitals in Northern Norway. The service is arranged by remote controlling microscopes with motorized X, Y and Z stage movements, magnification and illumination located at Kirkenes and Harstad Hospitals at a distance up to 400 km apart from the workstation at the University Hospital in Tromso. The video-images of the frozen section are transmitted via a two-ways phone and video telenetwork with 2 Mbit/s capacity. The images are displayed on a monitor as both still and live images and diagnosed by pathologists in Tromso. To data, 50 patients are examined by remote frozen section service. Correct benign versus malignant diagnoses are given in all cases compared with final diagnoses based on formalin fixed and paraffin embedded material except for two false negative malignant cases and two deferred diagnoses. The average time taken for examining each case of frozen section was 13 minutes. For hospitals with limited requirement of local pathology service and for hospitals with deficiency of specialists, remote frozen section service may be a worthwhile substitute. PMID- 1297434 TI - Experience and present status of telepathology in the National Cancer Center Hospital, Tokyo. AB - The optical fiber high definition television (HDTV) live image system with a remote control microscope is an ideal telepathology system. Diagnostic accuracy with this system is high enough for pathology consultation. However, it is very expensive to set up. The integrated services digital network (ISDN)-HDTV still image system using public telephone lines presently available in Japan INS 64 (64 kb/s), is not suitable for frozen section diagnosis and diagnosing difficult lesions. However, it functions very well for cytology consultation. When INS 1500 (1.5 Mb/s) becomes available in practice, it can substitute the optical fiber HDTV live image system in terms of cost and efficacy. Pathologists must become accustomed to making diagnosis from images on the monitor. They must be very careful in making diagnosis, when images are transmitted from institutions without pathologists, since selection error may occur at the time of frozen section and at the time of transmission of images. PMID- 1297435 TI - Telepathology: a new tool of pathology? Presentation of a French national network. AB - The field of pathology is constantly growing and the responsibility of the pathologists has progressively increased in the decision of application of some efficient but aggressive therapies. They justify the increasing necessity of discussion between pathologists about the diagnoses of difficult or rare or severe lesions. It is now possible to discuss at distance on good definition digitized images transmitted through I.S.D.N. A French experimental network between 12 workstations has been introduced since 2 years. Difficult or severe diagnoses have been immediately solved in 85% of the discussed cases. It remain legal problems and the necessity of an evaluation protocol which could be discussed at a European level. The increase of technical progress and, above all, the decrease of the costs might favour the development of telepathology. The workstation of the pathologist in the year 2000 could be the combination of a microscope, a HD-TV-camera and a personal computer with many softwares allowing treatment and transmission of numerous pictures. PMID- 1297436 TI - Telepathology in Greece. Experience of the Metaxas Cancer Institute. AB - This paper deals with the description of a telecommunication project which is initiated by Metaxas Pathology Laboratory. In the first section we discuss a comprehensive computer supported information system which was installed in the laboratory. Special emphasis is given at the design of the communication subsystem. Then, the configuration of the diagnostic equipment is described. The last section of the paper focuses on the discussion of the experimental use of an integrated "low cost" system for interconnection among the Metaxas Pathology laboratory, the Pathology Department of the University of Crete, and the Technological Educational Institute (TEI) of Athens. PMID- 1297437 TI - Telepathology in Sweden. A national study including all histopathology and cytology laboratories. AB - Quality improvement and standardization of diagnosis in histopathology and cytology are important for the future of the discipline. Nominal scale diagnoses dominate the practice and their standardization depends on relevant and reproducibly identifiable criteria as well as on communication of these among pathologists. Telepathology, i.e. the transmission of adequately detailed colour images of microscopic fields over the telephone network is now a realistic possibility. All 30 laboratories for histopathology and cytology in Sweden will have access to Telepathology work stations for at least 8 weeks each during 1992 1993. Two centers will have permanent stations from September 1992. The images will be transmitted over the ISDN network, allowing a compressed image to appear instantaneously. This image is then gradually and imperceptibly decompressed during 15-60 seconds, the time depending on the complexity of the image. A program for consultation and quality testing is being set up, which will be evaluated during 1993. Based on a recognition of the conditions for diagnosis in pathology and cytology indicated above, the Swedish Society of Pathology has initiated a project called "Telepathology in Sweden". It is a joint effort with active participation by Swedish Telecom and the Swedish Planning and Rationalization Institute for the Health and Social Services, Stockholm as well as by Innovativ Vision AB, Linkoping, a company providing hard- and software for image analysis, image banks and communication. PMID- 1297438 TI - Visual documentation of neoplasms as part of the REGISTRY Nomenclature Information System. AB - The REGISTRY Nomenclature Information system (RENI) is a program which runs on IBM-compatible personal computers. It includes internationally accepted diagnostic criteria for tumors and pre-neoplastic lesions in the rat to be used in toxicologic pathology. A video disk system, connected to the computer, provides colored pictures of histopathological reference slides, which are used for a visual documentation of the written criteria. PMID- 1297439 TI - Cloning of par region and the effect of par region on the stability of pUC9. AB - The par region of pSC101 was cloned into pUC9, and pEC302 was obtained. The stability of pEC302 and pUC9 in E. coli HB101 was tested on M9 medium to determine the effect of par region on the stability of plasmid. After 40 generations, pUC9 was almost completely lost, while pEC302 was 100% maintained in host cells. PMID- 1297440 TI - The establishment of rat-mouse hybridomas secreting anti-aflatoxin M1 antibodies and the properties of their monoclonal antibodies. AB - After a comparison of anti-AFM1-BSA antibody responses between rat and mouse, the spleen cells of rat with stronger responses were chosen as parent cells for fusing with mouse myeloma cells P3X63-Ag8.653. Through HAT medium selection, RIA screening and cloning, five well growing rat-mouse hybridoma clones were obtained that could secret anti-AFM1 antibodies stably. The results from ELISA and competitive binding RIA further proved that the 5 McAbs are direct against AFM1, with significant cross reaction to its derivative, AFB1. The average affinity constant of the 5 McAbs is 10(9)-10(11) l/M. It signifies that these monoclonals have potential application value for the construction of AF detection kit. PMID- 1297441 TI - Mass culture of anchorage-dependent animal cells with newly born calf skin collagen membrane and microcarrier. AB - It was shown that collagen substrate enhances the growth as well as the differentiation of many cells in culture. Collagen is one of the major fibrous proteins of animal bodies and the pure collagen used in this experiment was extracted from the newly born calf skin by chemical and biochemical methods. The analytical results obtained by ion-exchange chromatography and electrophoresis showed that the main components of denatured collagen were alpha monomers and beta dimers. The collagen and denatured collagen membranes were prepared by coating their solution on peteri dishes. Various types of cells were cultured on these membranes after being irradiated by ultraviolet ray. The denatured collagen was proved a good substratum for culturing anchorage dependent cells. A denatured collagen (gelatin) microcarrier, GT-2 was obtained by cross-linking gelatin with glutaraldehyde in a suspension polymerization process. These microcarriers were used successfully to culture various anchorage-dependent cells such as Vero, CHO, Bowes and fish cells in varying scales, including T-flasks, spinning bottles, revolving bottles and 1.5 l and 20 l bioreactors. PMID- 1297442 TI - A basic study on the hybridoma cell culture of microencapsulation. AB - We report here that the constitute component of Na alginate is a very important factor on microcapsular strength. We developed a method of estimating viable cell count in batch microcapsular process and the factors influencing the full loading rate in microcapsules. The physical integrity of microcapsule and full loading rate were greater than 95%. The cell line of C3 hybridoma was found to reach maximum intracapsule cell density of 8.8 x 10(6) - -2.1 x 10(7) cells/ml during static culture period of 6-10 days. During this period, the mouse monoclonal antibody accumulated in the intracapsular space to a final concentration of 379 micrograms/ml. Analysis of intracapsular protein by SDS gel electrophoresis during the culture period demonstrated that there was one band or two bands of protein which means its purity is relatively high. PMID- 1297443 TI - Location and trans-action of the pac regulatory gene. AB - The study on the localization of the pac gene indicated that the regulatory and structural genes were located in a 3.5 kb HindIII-EcoRI fragment. In this paper we report that a series of deletion derivatives of plasmid pPA6 was constructed and the effect of deletions on the pac expression was determined. The results suggested that the pac regulatory gene was located in the SphI-PvuII fragment within the pac structural gene. Then the SphI-PvuII fragment was cloned to the plasmid pTZ18U at the SphI-SmaI sites and the resultant plasmid pPA57 was transformed into the penicillin acylase producing strain E. coli D816 to observe the effect of SphI-PvuII fragment on the chromosomal pac expression. The results demonstrated that the regulatory gene within the SphI-PvuII fragment regulated the pac expression in trans. Computer analysis indicated that there were two ORFs in the SphI-PvuII fragment as possible candidates coding for the regulatory protein. The study on precise localization of the pac regulatory gene is in progress. PMID- 1297444 TI - High-level expression of recombinant protein A in Escherichia coli. AB - A high-level expression plasmid pPA-3 was constructed, which yielded up to 20% of soluble cell proteins as recombinant Protein A in E. coli DH5 alpha strain by heat shock induction. The recombinant Protein A contained only the five domains of native Protein A that bind with the Fc part of IgG. The molecular weights of the recombinant Protein A expressed in E. coli were determined to be 33kDa, 32.2kDa, 29.5kDa and 28.6kDa by SDS-PAGE and Western-blotting. The diversity of the molecular weights may be due to proteolysis, and a possible cleavage site is proposed. Some of the protein was purified with coupled human IgG by one-step affinity chromatography. The reactivity of the protein was compared with that of native Protein A and found that this protein could bind with more IgG than native Protein A in equal quantities of proteins. PMID- 1297445 TI - Construction of a genetically engineered strain producing propionylspiramycin. AB - Our work has demonstrated the cloning of propionyl acylase gene and the expression of S. mycarofaciens mutant in S. lividans TK54. In this paper, we report the transformation of pIJM9 recombinant plasmid containing the propionyl acylase gene into spiramycin producer S. spiramyceticus. The results of colony hybridization and Southern hybridization showed that No. 61 transformant harbored the pIJM9 recombinant plasmid. TLC and bioautography showed that the Rf value of one component of the fermentation products of No. 61 transformant was similar to that of propionylspiramycin. The HPLC retention time of the components of the fermentation products of No. 61 transformant and that of propionylspiramycin were also similar. Mass spectrum analysis showed that there was propionylspiramycin II in the fermentation products of No. 61 transformant. According to these results, No. 61 transformant is shown to be a genetic engineered strain producing propionylspiramycin. PMID- 1297446 TI - G-banding analysis of radiation-induced chromosome damage in lymphocytes of Hiroshima A-bomb survivors. AB - The present report describes the G-band analysis of somatic chromosomes in lymphocytes from 63 A-bomb survivors in Hiroshima to determine the type and frequency of radiation-induced chromosome aberrations. (1) The cells with stable type chromosome aberrations (Cs cells) predominated among the aberrant cells, and showed a dose-dependent increase. All stable chromosome aberrations were classified into nine categories: reciprocal translocations, translocations of complex type, insertions, complex exchanges, peri- and paracentric inversions, terminal and interstitial deletions, and unidentified rearrangements. The frequencies of aberrations were found to increase with increasing dose for all aberration categories. Reciprocal translocations predominate in all dose ranges and among the chromosome aberrations classified. (2) The linear model was fitted to test the dose-response relationship for Cs cell frequencies. Employing a constant neutron RBEs of 10, an estimated linear slope of 15.2%/Sv was obtained for DS86 bone marrow dose with an intercept of 2.9% at dose 0. (3) Statistical analysis of data on 3,370 break sites showed good correlations between relative DNA content and the distribution of chromosome breaks involved in translocations, although the involvement of chromosome 1 is significantly higher. PMID- 1297447 TI - Expression of the Tn antigen on erythroid cells from a patient with Tn syndrome. AB - In order to examine expression of the Tn antigen on erythroid cells from a patient with Tn syndrome, we applied a selective two phase liquid culture system for human erythroid progenitors in peripheral blood. The cells were analyzed with flow cytometry employing an anti-Tn antibody and a lectin of Vicia villosa which recognizes only the Tn determinant. In the second phase, the Tn antigen was expressed on the cultured cells from the patient on day 3 and Tn-positive cells reached 62.7% on day 9. On the other hand, Tn-positive cells were not detected in the volunteer's cultured cells. When the patient's cells were co-cultured with the cells from a healthy volunteer, the percentage of Tn-positive cells was much lower than the expected value, suggesting that the normal cells suppressed the expression of Tn antigen on the patient's cells. PMID- 1297448 TI - Allotypes of the fourth component of complement in Koreans. AB - The analysis of genetic polymorphism in C4 was performed on EDTA-plasma from 169 healthy unrelated Koreans. Plasma samples were subjected to high-voltage agarose gel electrophoresis followed by immunofixation. C4B allotypes were further detected by a hemolytic overlay method. The allele frequencies of C4A and C4B were as follows; for C4A, C4A*3 = 0.6099, C4A*4 = 0.1702, C4A*Q0 = 0.1525, C4A*2 = 0.0461, and C4A*R = 0.0213; for C4B, C4B*1 = 0.6406, C4B*2 = 0.2740, C4B*5 = 0.0569, C4B*Q0 = 0.0178, and C4B*R = 0.0107. C4A*3 and C4B*1 were among the most common alleles at each locus. C4A*6 was not detected in this study, but this allele is relatively common in both Caucasoid and Negroid populations. C4B*5 is a common allele in Asian, which is rare in Caucasoids and Negroids. C4B*5 appeared to be a characteristic allele of Oriental. In the C4A locus, five individuals with duplicated allotypes (three C4A 3,3 + 2, one C4A 4,3 + 2, and one C4A 3,3 + 3) were observed, and in the C4B locus, one individual with duplicated allotype (C4B 1,1 + 1) was detected. PMID- 1297449 TI - Population studies of INV(9) chromosomes in 4,300 Japanese: incidence, sex difference and clinical significance. AB - Population incidence of a chromosome 9 with an inversion of qh, inv(9), was surveyed using C-banding in a total of 4,367 Japanese which consisted of five patient groups and a normal control group. The inv(9) incidence was 1.65% in the normal control group (n = 1,513) and 1.52% in the Down syndrome patient group (n = 1,246). The incidence of female carriers was 1.7 times higher than that of male carriers in the above two groups. The sex difference was significant (p < 0.05). Moreover, the incidence in the 47,XXY male group (n = 277) was slightly higher than female carrier incidences. The excess of carriers about 2 times was observed in the habitual abortion couple group (n = 694) and the spontaneous abortus group (n = 181), both having normal karyotypes. The present data probably indicate the existence of a genetic effect of inv(9) on human reproductive performance, while they could not explain the sex difference found in inv(9) carriers. Our speculation for the sex difference has been presented. PMID- 1297450 TI - Localization of PMP-22 gene (candidate gene for the Charcot-Marie-Tooth disease 1A) to band 17p11.2 by direct R-banding fluorescence in situ hybridization. AB - We mapped PMP-22 gene, candidate gene for the Charcot-Marie-Tooth disease (CMT) 1A, by direct R-banding fluorescence in situ hybridization. The signals of PMP-22 probe were localized to chromosome band 17p11.2. The present result was within the map position of the CMT 1A gene by genetic linkage analysis, and strongly indicated that PMP-22 gene is a candidate gene for the CMT 1A. PMID- 1297451 TI - Localization of 24 cosmid clones on the human Y chromosome. AB - Twenty-four novel cosmid clones were cloned and mapped on the human Y chromosome using a panel consisting of DNA from seven individuals each having a different segment of the Y chromosome. Eight were assigned to the short arm, 15 to the long arm and 1 to the both short and long arms. PMID- 1297452 TI - Sex-determining region Y (SRY) in a patient with 46,XX true hermaphroditism. AB - Using a polymerase chain reaction method, a search for Y-specific DNA sequences was made in samples derived from tissues of a 46,XX true hermaphrodite. We found a sequence of SRY in the ovotestis, skin and leukocytes. Other DNA sequences, which covered the pseudoautosomal boundary region, amelogenin gene and DYZ1 locus of Y-chromosome were not detected. The SRY gene detected in the patient by the polymerase chain reaction was not detected by Southern blot analysis, using the SRY fragment as a probe. These findings suggest that in the patient there is a mosaicism of cells with and without part of the Y chromosome, including the SRY sequence. As the SRY sequence was responsible for the development of the gonadal primordium to the ovotestis, SRY seems essential for gonadal differentiation in testis development. PMID- 1297453 TI - Localization of pro-alpha 2(V) collagen transcripts in the tissues of the developing mouse embryo. AB - Correct assembly of fibrillar collagen networks plays a critical role in animal morphogenesis. Very little is known about the contribution of the so-called minor fibrillar collagens (types V and XI) to fibrillogenesis. Here we examined the developmental expression of the mouse pro-alpha 2(V) collagen gene (col5a2) after the cloning and sequencing of cDNAs that cover the entire length of the message. Transcripts of col5a2, detectable as early as 9 days of gestation, localize with distinct patterns in the tissues of day 12.5 and day 16.5 fetuses. The earlier developmental stage is characterized by low and diffuse col5a2 expression in the peritoneal membranes and intestinal and craniofacial mesenchymes. The later stage exhibits higher and more restricted col5a2 mRNA accumulation in primary ossified regions, perichondrium, joints, tendon, atrioventricular valve of the heart, and selected portions of the head. A parallel analysis using a cartilage-specific pro alpha 1(II) collagen (col2a1) probe confirmed that these two collagen genes are transcribed in a mutually exclusive manner during mouse embryogenesis. On the other hand, the developmental pattern of col5a2 expression closely resembles that of the type I collagen, thus further substantiating the notion that these macromolecules cooperate in the formation of fibrillar networks in non cartilaginous matrices. PMID- 1297454 TI - Localization of epidermal growth factor and its receptor in mandibular molars of the rat prior to and during prefunctional tooth eruption. AB - Immunoperoxidase localization of epidermal growth factor receptors (EGFR) and epidermal growth factor (EGF) itself was examined in rat first and second mandibular molars postnatally from day 0 to 12. The results showed that the dental follicle stained heavily for EGFR from day 0 to 8, declined in staining at day 9, and was devoid of stain from day 10 onward. Preosteoblasts and osteoblasts of alveolar bone also stained and lesser staining of ameloblasts and odontoblasts was observed. Except for staining of occasional isolated cells, the stellate reticulum did not stain. Light staining of the dental pulp of the first mandibular molar was seen from day 0 onward but the pulp of the second molar did not stain until approximately day 6. With respect to EGF, the dental follicle also stained for it until day 12. The ameloblasts stained more intensely for EGF than for EGFR. Because injections of EGF cause premature eruption of teeth and because the presence of a dental follicle is necessary for eruption, this study suggests that EGF could have its effect on the follicle as seen by the presence of EGFR receptors on the follicle. Moreover, because EGF exerts its effects early (day 0-3) to cause eruption and because the influx of monocytes into the follicle to form osteoclasts for bone resorption for eruption occurs early, the heavy staining for EGFR in the follicle early followed by the absence of staining at day 10 correlates chronologically with the key molecular and cellular events of eruption. Finally, the presence of EGF in the follicle, as well as enamel organ, could provide an endogenous source of EGF to regulate tooth eruption, either by an autocrine or a paracrine effect. Thus, the localization of EGFR and EGF in the dental follicle coupled with the chronology of localization suggests that EGF could play a physiological role in tooth eruption. PMID- 1297455 TI - Noncoordinate developmental regulation of N-cadherin, N-CAM, integrin, and fibronectin mRNA levels during myoblast terminal differentiation. AB - N-cadherin, N-CAM, fibronectin, and beta 1-integrins have been implicated in the control of myoblast fusion to form multinucleate myotubes, a critical step in the terminal differentiation of skeletal muscle. We have analyzed the temporal pattern of expression of mRNA transcripts encoding these adhesion molecules during the terminal differentiation of C2 mouse myoblasts. The accumulation of mRNA transcripts encoding N-cadherin, N-CAM, fibronectin, alpha 5-integrin, and beta 1-integrin subunits was developmentally, but not coordinately, regulated. N cadherin and integrin subunit expression was maximal in prefusion myoblasts and declined thereafter. In contrast, N-CAM mRNA levels were low in prefusion myoblasts, and increased coincident with the onset of terminal differentiation. Fibronectin mRNA levels were also low in myoblasts, and they did not increase until after cell fusion had occurred. The results indicate that despite their lack of coordinate regulation maximal levels of mRNA transcripts encoding adhesion molecules are present at a stage which corresponds to the peak of the active phase of myoblast fusion. PMID- 1297456 TI - Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus. III: Polyclonal origin of adjacent ventricular myocytes. AB - Replication-incompetent variants of the avian spleen necrosis virus (SNV) encoding cytoplasmic or nuclear-directed beta-galactosidase (beta-gal) have been used to trace the clonal growth of myocytes during left ventricular free-wall formation. Tubular-stage hearts were infected with a mixed suspension of both retroviruses and, after hatching, the progeny of marked cells in the ventricular wall were examined by X-gal histochemistry. When a small number of virions was introduced individual blue patches contained myocytes with only one label type (cytoplasmic or nuclear). These results confirmed our previous conclusion that each cluster or patch represents a single clone (Mikawa et al., 1992, Dev. Dynamics, 193:11-23). Each of these clones formed a clone-shaped patch which often extended through the entire thickness of the ventricular myocardium, but typically each patch was heterogeneous, containing a mixture of labeled and unlabeled cells. We then asked whether the two populations of myocytes in each patch were clonally related or generated from more than one progenitor. When hearts were infected with high titer viral suspensions many patches were observed in which cytoplasmic-tagged myocytes were intermingled with nuclear-tagged myocytes. Thus, the cone-shaped myocyte patches in the ventricular wall are polyclones derived from separate progenitors in the precardiac mesoderm. This finding led us to examine the separation of clonally related ventricular myocytes in the developing hearts. Embryos were infected with retroviral suspensions at varying stages of development and the resulting colonies examined after hatching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297457 TI - Comparison of Hensen's node and retinoic acid in secondary axis induction in the early chick embryo. AB - Retinoic acid (RA) and Hensen's node, the organizer center in the chick embryo, have been shown to have polarizing activity when applied or grafted into the chick limb bud. Here we investigate and compare the effects of RA and grafted Hensen's node on the early chick embryo. Anion exchange beads soaked with RA at concentrations ranging from 5 to 100 ng/ml and implanted on the anterior side or on the left side of the host anteroposterior axis of a stage 4 chick embryo in ovo have the ability to induce secondary axis formation, while beads soaked with RA of the same concentration and implanted on the right side or on the posterior side of the host axis are unable to induce the secondary axis. All of the induced axes contain trunk-tail structures. Hensen's node from quail embryos implanted into the early chick blastoderm could also cause the formation of secondary axes in addition to self-differentiation of the graft into a secondary axis. Both RA and grafted Hensen's node caused the inhibition of forebrain development with an increase in hindbrain development and the host heart to loop in an abnormal direction. The results support the hypothesis that Hensen's node is a source of RA which is involved in early embryogenesis. Alternatively, RA might stimulate the formation of Hensen's nodal properties in adjacent tissue. PMID- 1297458 TI - Optic chiasm and infundibular decussation sites in the developing rat diencephalon are defined by glial raphes expressing p35 (lipocortin 1, annexin I). AB - p35, a Ca(++)-phospholipid-binding protein that serves as a substrate for the EGF receptor tyrosine kinase, is expressed by primitive glial ependymal cells to define a raphe occupying the ventral midline in the spinal cord and hindbrain of rat embryos (McKanna and Cohen, Science 243:1477-1479, 1989). p35 appears transiently in the median one-third (80 microns) of the floor plate at precisely the time and place where axons cross to form the ventral commissure. We postulated that if p35 is involved with commissure development, homologous p35 raphes might be found at decussation sites rostral to the floor plate, including the optic chiasm. The present report describes two developmentally regulated p35 raphes in the diencephalon. One raphe is present for 2-3 days at the rostral lip of the nascent infundibulum, the reported decussation site of axons running from the supraoptic nucleus to the neurohypophysis; the other raphe appears in the rostral two-thirds of the optic chiasm, the site traversed by the optic axons. p35 is never expressed in the caudal one-third of the chiasm that accommodates non-retinal axons. To the best of our knowledge, this is the first identification of a specific marker for the retinal component of the optic chiasm. Because the p35 is gone by embryonic day 18.5, it is absent during final stages of chiasm formation when axons from the temporal retina decussate. Thus, p35 also may contribute to the "barrier" perceived by fibers that remain ipsilateral. Our data suggest that the p35 raphe contributes to the midline's role in commisure morphogenesis. Putative lipocortin activities including regulating PLA2, eicosanoids, or intracellular Ca++ could be involved in altering cue specificity as decussating axon growth cones traverse the p35 compartment. PMID- 1297459 TI - Expression of collagenase and IL-1 alpha in developing rat hearts. AB - During development, extracellular matrix (ECM) molecules are thought to play a major role in regulating the formation of the heart. The change in the heart from a simple tube to a complex, four-chambered organ requires the modification of both the cellular components as well as the surrounding ECM. Matrix metalloproteinases (MMP), which include collagenases, are enzymes present in the ECM that have the potential to modify the existing ECM during the development of the heart. Using both monoclonal and polyclonal antisera against collagenase, specific temporal and spatial patterns have been documented during critical periods of heart development. The cytokine interleukin 1 alpha (IL-1 alpha), a potent inducer of the MMP expression, was also shown to have a similar staining pattern in the developing heart. The monoclonal anti-rat collagenase (Mab) intensely stained the surfaces of the myocytes in the trabeculae and the ventricular and atrial walls of the 11.5 or 12.5 embryonic day (ED) rat hearts. In contrast, the polyclonal anti-human collagenase (Pab) stained not only the cardiomyocytes but also the hypertrophic endocardial cells. Pab appeared to stain the leading edge of the mesenchymal cells that migrate into the cardiac jelly of the 11.5 or 12.5 ED hearts. Immunohistochemical staining showed IL-1 alpha on the endocardial endothelium and the surface of cardiomyocytes near the cardiac jelly just before or coincident with the appearance of migrating cells. IL-1 alpha was detected on the endocardial endothelium, cardiomyocytes in the trabeculae, and the ventricular and atrial walls, as well as in the myocardial basement membrane of the truncal or atrioventricular region. However, no staining could be detected on the migrating cells in the cardiac cushions. These results indicate the presence of collagenase and IL-1 alpha on the surface of cardiomyocytes and mesenchymal cells at times when the heart is undergoing acute remodeling during septation and trabeculation. These data suggest a role for collagenase/cytokine interaction in tissue remodeling during critical stages of cardiac embryogenesis where modification of the ECM is essential to cardiac morphogenesis. PMID- 1297460 TI - Study of the behaviour of the mumps virus in different cell culture systems. AB - The Enders reference strain of the mumps virus was cultivated on various systems (chicken embryonated eggs, chicken embryo fibroblast cultures, Vero cell cultures) to develop a model of preparing and controlling the production of the mumps vaccine in Romania. The results have proved that the monolayer of chicken embryo fibroblast is a suitable cell culture system for the multiplication of the mumps virus, and on the Vero cells the virus can be quantified just like the live measles vaccine. PMID- 1297461 TI - Investigations concerning the possibility to replace the Schick test by the passive hemagglutination reaction for evaluating the diphtheria immunity level in population. AB - The evaluation of Schick test results as compared to the results obtained by determination of diphtheria antitoxin concentration in blood using the neutralizing test on rabbit--Jensen on the one hand and to those obtained by the passive hemagglutination reaction on the other has revealed some discrepancies against the two tests: 7.09% (4.08% pseudo-protected, 3.01 pseudo-susceptible) as against TN-Jensen and 8.6% (5.59% pseudo-protected and 3.01% pseudo-susceptible) as against the passive hemagglutination reaction results. The reported discrepancies were due to the fact that the results of Schick test did not correlate perfectly with the amount of circulating antitoxin, the diphtheria immunity level was wrongly indicated by the Schick test. The passive hemagglutination reaction has proved to be adequate to mass-screening investigations being capable to replace Schick test. PMID- 1297462 TI - Hemolytic properties of some Aeromonas strains. AB - Considering the possible correlation between hemolytic and enterotoxigenic properties of Aeromonas strains mentioned in the literature, in the present work we studied the practical value of the hemolysis tests in the diagnosis of Aeromonas strains by using comparatively the hemolysis tube tests (with goat and sheep erythrocytes suspensions) as well as the technique on blood agar in aerobic conditions. There were studied comparatively 230 Aeromonas strains (different species: A. hydrophila, A. sobriae, A. caviae, A. veronii, A. salmonicida) isolated from different sources (meat products, fish of fresh waters, mussels, sea water, pipe water, diarrhoeal disease and animal faeces). The comparison among the used tests for proving the hemolytic activity of Aeromonas strains showed that: 61.89% and 56.51% from the total number of Aeromonas strains were hemolytic in the tube tests with 1% goat and 1% sheep erythrocytes suspensions respectively after 48 hrs followed by 51.72% and 48.25% strains by the 5% goat and 5% sheep blood agar plates respectively in anaerobiosis and after 48 hrs incubation at 37 degrees C. The highest incidence of hemolysin presence was pointed out in motile Aeromonas strains (A. hydrophila--60.11% and A. sobria- 56.52%). Our results showing a high frequency of hemolytic activity among Aeromonas strains isolated especially in meat products are suggesting a possible correlation between the pathogenic potential and the hemolytic activity and are pleading for introduction of this test in the diagnosis of Aeromonas species. PMID- 1297463 TI - Evaluating the minimum active concentrations of penicillin G and V and of retard forms in clinical conditions. AB - Following several signals indicating the inefficiency of the clinical treatment with various penicillin preparations in some cases, we decided to study the seric penicillin concentrations in the patients hospitalized in the "V. Babes" Hospital of Infectious Diseases, after administration of the various Romanian made forms of penicillin currently used in the therapy of streptococcal infections and in the prophylaxis of the sequelae of these infections. The data obtained on groups exceeding 30 persons by using two methods of determining the penicillin concentrations the dilutions and the diffusimetric methods revealed protective penicillin seric levels satisfactory for penicillin G and Efitard, according to the present treatment schemes. After 5 days from Moldamin administration only 45.4% of children and 43.3% of adults were found to have satisfactory penicillin concentrations. The administration of penicillin V reaches active penicillin concentrations in terms of the dose administered. The paper points out only one of the causes which together with others (such as beta-lactamase production and tolerance), contribute to the unsuccessful treatment with various forms of penicillin. PMID- 1297464 TI - Group B streptococci implicated in the etiology of acute pneumopathies in neonates. AB - 111 neonates with acute respiratory insufficiency and/or severe pneumopathy (pneumonia, bronchopneumonia) occurring in the first 10 hours after birth were investigated during January 1990-September 1991 for the group B streptococci presence. 430 samples from these neonate cases: throat and nose exudates, necroptic material from died neonates (pulmonary, blood, bronchial secretion) and their mothers (lochia, vaginal and uterine secretion) were examined. 33% of the neonates and their mothers were positive with the same GBS. 65.30% from the GBS strains belonged to serotype Ia and 34.70% to Ib. 24.48% from the GBS strains were resistant to Penicillin G by diffusimetric method with a corresponding MIC of 0.1 UP/ml (22.12%) and 0.5 UP/ml (2.65%). PMID- 1297465 TI - Sensitivity to penicillin of S. pneumoniae strains isolated from various pathological conditions. AB - 297 S. pneumoniae strains isolated from patients with different pneumococcal infections during 1990-1991 were tested for the sensitivity to antibiotics--by the diffusimetric method to 9 antibiotics (Penicillin (6 micrograms), Ampicillin (10 micrograms), Erythromycin (15 micrograms), Oxacyllin (5 micrograms), Streptomycin (50 micrograms), Tetracycline (50 micrograms), Chloramphenicol (50 micrograms), Rifampicin (6 micrograms), and Kanamycin (30 micrograms) and by MIC determination to Penicillin and Erythromycin. 30% of S. pneumoniae strains were resistant to Penicillin and Erythromycin corresponding to a MIC > or = 1 UP/ml or > or = 1 microgram E/ml. The most active antibiotics were Chloramphenicol and Rifampicin and the less active: Tetracycline, Kanamycin and Streptomycin. A relation between the origin and serotype of the strains and the sensitivity to antibiotics was revealed. The strains from the throat, conjunctive and otic secretions and belonging to serotypes 19, 6 and 14 showed the highest levels of resistance to all antibiotics. A good correlation between MIC and diffusion method results was observed to Erythromycin and no correlation to Penicillin. In this last case the results of MIC determination to Penicillin were better correlated with the results of inhibitions diameters to Oxacyllin, method which have to be recommended. PMID- 1297466 TI - Study of strains agglutinable with enteroinvasive anti E. coli polyvalent sera isolated from ill and healthy subjects for optimizing the laboratory diagnosis of diarrhoea. AB - 369 E. coli strains that are agglutinated in A or B anti E. coli enteroinvasive (EIEC) polyvalent sera and inducing no keratoconjunctivitis in the guinea pig's eye have been selected. The biochemical reactions of E. coli strains that can be agglutinated in A or B EIEC polyvalent sera occupy an intermediary position between those of Shigella genus and the classical features of Escherichia, i.e.; 87% are motile bacteria, 88%--ferment lactose, 81% form acid from sodium mucate and lysine is not decarboxylated by 87% of the strains. As for the antigenic behaviour with 15 out of the 16 sera employed, the strains under consideration have agglutinated by slide test in one or several sera, with varying intensities. None of the strains agglutinated on slide in the O164 antiserum. Subsequently, agglutinations have been performed in tubes only with the strains that agglutinated on the slide with a +3 or +4 intensity. Out of the 369 strains under consideration only 25 have agglutinated in the tube, all the false positive reactions representing 6.7%. The data presented lead to the conclusion that such strains that have been isolated from ill or healthy patients cannot be considered as pathogenic diarrhoea agents, the differentiation from the invasive strains (in the absence of the guinea pig for the pathogenicity test) cannot be made on the basis of the biochemical reactions, but only by means of a set of monovalent sera and by performing the tube agglutination tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297467 TI - Spectrophotometric assay of the interaction of Plasmodium berghei infected erythrocyte lysates and neutral red. AB - In order to reveal by absorption spectrophotometry the redox differences between the Plasmodium berghei infected erythrocyte lysates (MEL) and the healthy ones (HEL) we studied their interaction with the neutral red (NR) redox dye. The variation of the dye absorption intensity at 540 nm as a function of the hemoglobin content of the samples was attributed to the redox potential variation of the different hemoglobin aggregates formed in the samples containing different hemoglobin quantities. By short term treatment of the lysates with ascorbic acid in the presence of NR, great redox reactivity difference was proved between MEL and HEL as revealed by absorption and explained by the initial higher oxidation state of the Hb iron in MEL than in HEL. PMID- 1297468 TI - Simultaneous recording of urethral pressure and cross sectional area profile. AB - A new technique for simultaneously recording urethral closure pressure and cross sectional area profile is described. The cross sectional area of the urethra could be measured using the field gradient principle. The procedure was performed readily in male patients and the recordings can be graphically presented during measurement. A high degree of reproducibility using this method was obtained. Typical recordings of control subjects was well as patients with pathology were obtained using this technique. The results of this study show that the maximum urethral closure pressure obtained was 60.8 + 3.4 mmHg and functional profile length, 4.8 + 0.4 cm. Internal meatus cross sectional area was 0.67 + 0.04 cm2 and the minimum urethral cross sectional area was 0.12 + 0.02 cm2. This method has been shown to be readily applicable in measuring urethral closure pressure in males and can potentially be used as a tool of comparing the functional parameters of pressure with the anatomical value of diameter. PMID- 1297469 TI - [Effect of AS-4370 on gastric motility in patients with diabetic autonomic neuropathy]. AB - Delayed gastric emptying in diabetic patients occurs with progress of automatic neuropathy as one late complication. Delayed emptying is deeply correlated with poor glycemic control, due to imbalance between nutrients absorption and effect of exogenous insulin. AS-4370 is a newly developed prokinetic agent which has been reported to selectively activate motility of the upper gastrointestinal tract through enhancing acetylcholine release from nerve terminals within the enteric mural plexus. In this study, we evaluated the effect of AS-4370 on gastric motility in diabetic patients with autonomic neuropathy. Eight diabetic patients with autonomic neuropathy (3 males and 5 females) with mean age of 56 years old (range 29-66) participated to this study after giving written informed consent. Gastric motility was evaluated by gastric emptying and electrogastrography. Gastric emptying study was done using 99mTc-Tin colloid labeled omelet meal served with 2 slices of toast and 200 ml of milk. Electrogastrography was recorded from epigastric skin surface, for 30 minutes before and after meal each. AS-4370, 7.5 mg tid, was given for four weeks after basal recording of gastric motility studies. Following the 4-week treatment with AS-4370, gastric motility studies were repeated. For the motility studies after medication, drug was given 30 minutes before test meal. Gastric retention rate at 150 minutes in all patients were over 45% of upper limit of normal range in basal study with mean value of 69 +/- 5%, which decreased significantly to 52 +/- 5%, with AS-4370 treatment (p < 0.01). Gastric emptying speed, another parameter for gastric emptying also improved with medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297470 TI - [The effect of 2 bleaching agents on the enamel surface. An in-vitro study]. AB - We present a study "in vitro" of the effect of bleaching agents on dental surfaces using the "Walking bleaching technique". We found that hydrogen peroxide bleached more quickly than carbamide although, after a period of six weeks, the results were the same as far as whitening was concerned. In the scanning electron microscope we observed significantly different changes in each case. Carbamide caused a regular and uniform opening of the enamel prisms of the surface while hydrogen peroxide produced more severe superficial destruction with the appearance of patterning similar to the acid etching, and the presence of some crystalline areas emerging from the body of the prisms. PMID- 1297471 TI - Morphometric computerized analysis on the dentinal tubules and the collagen fibers in the dentine of human permanent teeth. AB - A morphometric analysis has been performed on important components of human dentine using an image computerized analyzer. The dentinal tubule diameter and their area percentage were calculated. Moreover the area percentage of the collagen fibers in the dentinal matrix was measured. These parameters have been evaluated in different areas of the coronal and the radicular dentine in permanent teeth. Measurements have been performed on undecalcified and decalcified teeth and on teeth treated with enzymatic digestion to remove the organic non collagen matrix and to evidentiate the collagen fiber network. The values obtained in different areas of the tooth and in samples submitted to different treatments were evaluated by statistical analysis. Dentinal tubule diameter and area percentage significatively decrease from the inner to the peripheral dentine both in the undecalcified teeth as in the decalcified ones and in the samples undergone to enzymatic digestion. The collagen fiber percentage in the organic matrix is significatively lower in the mantle dentine. PMID- 1297472 TI - [The bone structure of the ramus of the mandible]. AB - Osseous structure of the ramus of mandible (RM) is of a practical clinical significance. Osteosynthesis of fractured segments and the success of the sagittal or the horizontal ramus split osteotomy depends on the cortical bone disposition and thickness. After morphometric investigations of the RM, conducted on 70 mandibles of adults, consecutive horizontal and frontal sections were made. On these sections, the cortical layer was studied and the cortical bone thickness was measured at four previously marked points. In the regard of morphometry, the significant datum is that nearly half of all the cases is grouped round the mean value of any parameter. Cortical bone is continuous and its two main sheets are the buccal and the lingual cortical plates. In its entirety, the buccal cortical plate is thicker than the lingual. The thickness of both cortical plates increases in the direction from the coronoid process to the angle of mandible. PMID- 1297473 TI - [Light and electron microscopy observations on different tissues of a complex odontoma]. AB - Several aggregates of dental tissues constitute the complex odontoma. They are almost completely covered by a layer of prismatic enamel. By the observations at transmission and scanning electron microscope enamel present the characteristics of a not fully developed tissue. The organic component is still abundant and the enamel surface is covered by a cellular layer having the morphological features of the mature ameloblasts. Therefore this enamel results to be yet actively engaged in the maturation phase although the tissues of the odontoma have generally a limited developing time. PMID- 1297474 TI - [Enamel pearls: the ultrastructural aspects and morphogenesis hypotheses]. AB - Five enamel pearls were examined by scanning electron microscope. Some external pearls presented a bare enamel surface, others were covered by a thin layer of cementum. The enamel pearls showed irregular dystrophic enamel surface or a thin layer without structure, rows of irregular Tome's processes pits, enamel caps and focal holes. Some enamel pearls revealed little areas of enamel surface resorption like-resorbing lacunae with, in some cases, areas of tissue repair. PMID- 1297475 TI - NaOCl and EDTA irrigating solutions for endodontics: SEM findings. AB - Premolars roots of humans were manually instrumented with K-type files and irrigated with different solutions to evaluate the rate of cleaning of endodontic surface. Root canals irrigated with 0.9% saline solution or H2O2 (10 volumes) showed the presence of predentin and amorphous smear layer. Thick smear layer was always present on endodontic walls rinsed with 5% solution of NaOCl. Specimens treated with 0.2% solution of EDTA showed partially clean dentinal tubules orifices and remnants of a thin smear layer. Occasional uninstrumented areas of the same roots presented smear layer remnants and predentin with calcified bacteria. The root canals irrigated with NaOCl and EDTA solutions alternated after each instrument showed at the dentin surface thick smear layer: only few dentinal tubules orifices were visible. Endodontic surface of root canals irrigated with NaOCl during instrumentation and finally rinsed with EDTA solutions showed the most homogeneous ultrastructural pictures: partially clean dentinal orifices were detectable in the whole canals. PMID- 1297476 TI - [The effect of the magnification ratio on 2 methods of computerized image analysis in scanning electron microscopy]. AB - The aim of this study is to compare two computerized analysis methods of SEM dentinal walls views. The first technic is an indirect one using a primary marking and a secondary measurement. The second one is a direct threshold analyse, using the grey levels selection. The influence of the magnification is analysed in a second part. The first technic is considered as a reference one. The results show that the threshold measurement technic is only reliable at a high magnification. A direct surface measurement cannot be used at a low magnification. A pretreatment could enhance the ability of a computer to measure the areas covered with smear-layer or organic debris on SEM micrographs. PMID- 1297477 TI - c-myc hypermutation in Burkitt's lymphoma. AB - Translocation between the c-myc protooncogene and one of the three immunoglobulin loci is a cytogenetic hallmark of the B cell tumor, Burkitt's lymphoma. The resulting deregulation of c-myc expression is a critical step in tumorigenesis. The translocation breakpoint may lie within c-myc proper, in which case deregulation is due, in part, to dissociation of key 5' regulatory sequences from the protein-coding portions of the gene. Alternatively, the breakpoint may flank c-myc, leaving the gene grossly intact. In these latter cases, mutation, which may be extensive, is usually seen within c-myc, specifically at or near the same key regulatory sequences. The precise contribution of these mutations to c-myc deregulation is gradually being clarified. The mechanisms underlying c-myc mutations are not known. Hypermutation in c-myc may reflect the influence of the juxtaposed immunoglobulin gene, which is subject to hypermutation during an intermediate stage of normal B lymphoid development. This relationship, however, has not been firmly established. PMID- 1297478 TI - Human interleukin-9: a new cytokine in hematopoiesis. AB - IL-9 was first identified in the mouse system as a T cell growth factor while human IL-9 was isolated based on its activity on a human myeloid leukemic cell line. The high sequence homology between mouse and human IL-9 plus the preliminary biological analysis have predicted a wide spectrum of in vitro biological activities for this cytokine. Despite the high sequence homology between mouse and human IL-9, many biological activities, however, have not been demonstrated in both species. In vivo studies therefore become essential to understand the physiological role of IL-9. Increasing evidence have also suggested the possible role of IL-9 in the pathogenesis of HD and LCAL. Detailed analysis of IL-9 expression, autocrine growth and clinical outcome of HD patients will be required to make any speculation on the role of this cytokine in the disease states. PMID- 1297479 TI - The interleukin 2 receptor in the hypereosinophilic syndrome. AB - The hypereosinophilic syndrome (HES) has been previously described as a clinicobiological entity characterized by a blood eosinophil count of over 1.5 x 10(9)/L of unknown cause associated with several clinical complications. In reality, HES is a heterogeneous group of diseases with variable and unpredictable progress in visceral lesions, thought to be related to the deleterious effects of tissue eosinophil infiltration. Various criteria for discrimination between benign and severe forms of HES have been described. These previous retrospective clinical investigations, using biological and clinical markers, have defined different stages of HES. It appears more relevant, however, to consider elements of disease activity by studying mechanisms of induction of persistent hypereosinophilia. The T-cell dependence of blood eosinophilia has led us to evaluate various markers of T-cell activation in particular. In the present review, we report previous results and perspectives suggested by the study of the interleukin 2 receptor in HES. PMID- 1297481 TI - The value of the bone marrow plasma cell cytoplasmic light chain ratio in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance. AB - We compared the plasma cell light chain ratios in the bone marrows of 13 patients with multiple myeloma (MM), with those of 13 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean light chain ratio in favour of the paraprotein isotype in the myeloma group was 51.83 (95% confidence limits (CL) 29.52-74.14), while in the MGUS group it was 5.30 (CL 2.07-8.52). The difference between the MGUS and MM groups was significant (p = 0.0005). Neither the bone marrow plasma cell count nor the paraprotein level were significantly correlated with the light chain ratio in either of these two groups. We found a cut-off ratio of 8 to be the most useful in differentiating between myeloma and MGUS. Only one patient with myeloma had a ratio below 8, and one MGUS patient had a ratio above this cut-off point. We conclude that determination of the bone marrow plasma cell light chain ratio is a simple and useful test in differentiating between myeloma and MGUS in difficult cases. PMID- 1297480 TI - Transient abnormal myelopoiesis in Down's syndrome. AB - Recent data have elucidated the pathogenesis of transient abnormal myelopoiesis (TAM) to a great extent. TAM is a monoclonal disorder which resolves spontaneously and the target cell in this disorder is a multipotent stem cell which is capable of differentiating into megakaryocytes. The pathogeneses of TAM/AMKL (acute megakaryoblastic leukemia) appears to be closely associated with abnormal quality and quantity of a gene located on chromosome 21. AMKL developing after the regression of TAM appears to come from the same clone as the TAM, which apparently experiences some kind of genetic alterations. It seems that the gene responsible for TAM will soon be cloned in the near future. However, the mechanism of spontaneous regression of TAM has as yet not been clarified. The expanding clone in the transient physiological immunodeficient state, during the perinatal period, might be eliminated with the maturation of more mature immunosurveillance. Alternatively, the TAM clone might be destined to undergo spontaneous death, which is called "programmed cell death" (apoptosis). The mechanism of this phenomenon awaits further elucidation. PMID- 1297482 TI - Pulmonary involvement as the major manifestation of chronic lymphocytic leukemia. AB - Respiratory symptoms and abnormal findings on chest X-ray are frequently noted in patients with chronic lymphocytic leukemia (CLL). However, most of these represent pulmonary infections or mediastinal lymphadenopathy, and leukemic involvement of the lung is seldom diagnosed during life. In this report we describe three patients with non-progressive, responsive CLL who developed biopsy proven pulmonary infiltration with CLL. In one case, pulmonary involvement was the sole manifestation of recurrent disease and a second case had little disease elsewhere with minimal CLL in the blood at the time pulmonary involvement appeared. In all three cases, transbronchial biopsy and bronchoalveolar lavage performed during fibreoptic bronchoscopy provided adequate tissue for diagnosis. We conclude that CLL may involve the lung even in the presence of a low peripheral white blood cell count with responsive disease elsewhere, and can readily be diagnosed by transbronchial biopsy and bronchoalveolar lavage. PMID- 1297483 TI - Polycythaemia vera following non-Hodgkin's lymphoma. AB - A patient with non-Hodgkin's lymphoma (NHL) who developed polycythaemia vera (PV) is reported. Diffuse large-cell NHL was diagnosed and he was subsequently treated with combination chemotherapy including high dose cyclophosphamide and procarbazine. Four and a half years after chemotherapy splenomegaly developed, coincidently with the appearance of high Hb values, RBC and platelet counts. The screening tests for PV were consistent with this diagnosis, while the search for lymphoma activity was negative. To the best of our knowledge, the present case represents the first well-documented instance of PV following NHL. PMID- 1297484 TI - Urinary bladder cancer following cyclophosphamide therapy for Hodgkin's disease. AB - Urinary bladder cancers following prolonged cyclophosphamide therapy are being increasingly reported. We report a case of transitional cell carcinoma of the urinary bladder occurring 12 years after pulse intravenous therapy with cyclophosphamide for Hodgkin's disease. The mechanism of bladder carcinogenesis and the possible role of the uroprotector MESNA in preventing cyclophosphamide induced bladder cancer are discussed. PMID- 1297485 TI - [The psychophysiological bases for the training of flight personnel for operations in contingency situations]. AB - The paper deals with the psychological and physiological mechanisms characterizing the behavioral patterns of a pilot under emergency situations. In a regular flight, the most important psychic regulator is a target-image and predicting of an assigned task performance serves as the mechanism of its implementation. In non-routine situation, the regulation pattern is significantly changed. Under emergencies, there exist two levels of pilot responses: adaptive defensive reactions which activate the automated acts and evaluation-decision making ones which promote intellectual transformations of information to compare the conceptual and information models. In order that under emergency the pilot response be successful the specific mental skills are needed to promote the rate of abstraction and determination of key sings which are the basis for decision making. Experimental data on the reliability and adequacy of pilot response in real flight under simulated contingencies are presented. Typical disorders of cognitive psychic processes, behavioral disorganization under these conditions have been described. The components of psychophysiological adequacy of pilots and principles and means of its creation are discussed. PMID- 1297486 TI - [The principles of constructing a data bank applicable to the problem of physiological standards in space medicine]. AB - The norm is a more complex problem in physiology and in space medicine in particular. Definition of norm and health concepts is analyzed. Classification of functional states based on the adaptation and homeostasis concepts is proposed. Various approaches to determination of a norm are described. Three types of the norms which are of significance for space medicine, namely rest norm, reaction norm, adaptive norm are identified. The structure of data bank containing information on the standards is described. The central data bank structure is considered. PMID- 1297487 TI - [Altitude stress and the training of cosmonauts]. AB - An ergonomic concept of the development of altitude stress is presented. According to this concept, the altitude stress as a psychophysiological response of man to the risk of falling from altitude is determined by the number and placement with respect to man position of antifalling contact supports and those being non-contact, i.e., potential supports capable of preventing the fall when changed a situation with the structures. The analysis indicated that this concept is also applicable for describing the extravehicular locomotion of cosmonauts with the use of the supports on the basis of which the preliminary ground preparation of cosmonauts using altitude-spatial trainer becomes possible. PMID- 1297488 TI - [The methodology for clinical trials of radiation-protective agents intended for the conditions of manned space flights]. AB - The methodology of clinical testing of antiradiation measures to be used in manned space missions is proposed and discussed. The tests should be based on: an individual tolerance to a recommended medicinal form of the drug; the tolerances to the effects of motion sickness, prolonged transverse and longitudinal accelerations; graded physical exercise; evaluation of performance (operator activity). PMID- 1297489 TI - [Adaptation to anthropogenic chemical compounds in human applied ecology]. AB - The literature data pointing to the fact that man can actively adapt to the effect of chemical substances at doses not exceeding hygienic norms are presented. However using some medical measures it is possible to increase to some extent the body resistance to the effect of chemical impurities of the environment and thus delaying for some time the development of disadaptation disorders induced by these impurities. PMID- 1297490 TI - [A. V. Lebedinskii and his contribution to the development of aerospace medicine (on his 90th birthday)]. PMID- 1297491 TI - [The cabin microflora of manned space vehicles and the problem of the biological destruction of the construction materials used in them]. AB - It is found that during operation of manned space objects there can occur the microbial growth on the structural materials of cabin interior and equipment which results in their biological destruction. The biodestructing processes can involve single parts of cabin interior, trainer linkages, connectors, cables, illuminators. Ninety four microbial species have been identified in spacecraft environment. The bacterial flora was presented by 19 genera pertaining to 11 families and involved 58 species. The mold and yeast-like fungi were presented by 12 genera and consisted of 36 species. The significant quantities of isolated microbial species were classified as potentially pathogenic microorganisms; many of them are known as biodestructers of polymeric materials. The isolated microbial cultures in space missions have become the basis of strain bank intended for further study and practical use in validating the construction materials. PMID- 1297492 TI - [The cardiovascular system function of the cosmonauts of the 6th prime expedition on the Mir station]. AB - Medical results of inflight cardiovascular measurements made in the 6th prime crew at rest and during provocative graded bicycle exercises and LBNP tests are presented. The methods of electrocardiography, tetrapolar rheography, kinetocardiography, arteriovenous pulsography and tacho-oscillography have been used to examine the cosmonauts. Together with regular cardiovascular changes typical of microgravity effect the individual peculiarities of developing the control mechanisms are noted. Thus in one of the cosmonauts a number of symptoms responsible for a decreased venous return. As a whole the functional state of the cardiovascular system on all flight stages was characterized by a sufficiently high physiological level. PMID- 1297493 TI - [The ultrasonic location of gas bubbles in the human bloodstream during work in a spacesuit]. AB - The results of testing a procedure of ultrasonic location of the gas bubbles (GB) in man during space suit operations to simulate an extravehicular activity (EVA) are presented. Doppler echotachocardiograph "Rhythm" operating at ultrasonic frequency of 1.76 mHz was used as a GB detector. The device "Rhythm" integrated with a special flat transducer of 23 mm in diameter and 4 mm in width was positioned on the subject chest above the pulmonary artery projection. During 4-6 hour human operations while wearing pressurized (276-290 mm Hg) space suit, in 7 of 12 tests performed a stable and qualitative signal of the arterial blood flow in the lungs was recorded. In case of an unstable signal, in order that its quality be improved the posture of test subject was changed and the signal was recorded during a short-term expired breath-holding. Cardiac GB formation was noted during 6 tests in 2 subjects. The first GBs appeared at the 30th, 33rd, 70th, 111th, 114th and 180th minute after producing an operating reduced pressure in space suit. The time of GB detection on the average was 89.7 min. The maximum intensity of GB signal was 3-4 scores on Spencer's scale, but altitude decompression sickness symptoms did not develop in the test subjects. The risk of developing the altitude decompression sickness as opposed to the results of control experiments without use of space suit is discussed. PMID- 1297494 TI - [Morphological research on the liver structures of experimental animals under the action of infrasound]. AB - Data of the experimental investigations of the effects of infrasound (frequencies: 2, 4, 8, and 16 Hz; acoustic pressure: 90, 100, 110, 120, 130, and 140 dB) on hepatic structures of laboratory animals are presented. Single exposure to infrasound with any of the given parameters induces no changes in hepatic structures. Such elements of the liver as hepatocytes and small vessels turned out to be most sensitive to 3 h./d infrasonic exposure during 5 to 40 days. Alterations in the liver were local by nature and manifested by ischemic areas with hepatocyte morphologic and histochemical changes. Hepatocyte changes after 5 to 40-day infrasonic exposure showed increased functional activity. More durable exposures (25 and 40 days) yielded irreversible changes in hepatocytes. These results indicate that 8 and 16 Hz infrasound produces more pronounced histological, histochemical and ultrastructural alterations than 2 and 4 Hz. These data suggest that the above frequencies can indirectly impair cell organoids and nuclear chromatin, and affect the hepatocyte function. PMID- 1297495 TI - [The asthenic syndrome and mental work capacity]. AB - Investigation of the development of the asthenic syndrome during neuropsychic overload and its impact on dynamics of psychic performance in operators is of great interest to many specialists engaged in clinical and applied medicine. The paper presents results of clinicopsychologic and clinico-neurophysiologic studies of 105 persons in intellectual and operational professions who were treated in Moscow Clinic of neurosis in connection with the asthenic syndrome caused by professional overload or emotional stress. The obtained data showed that development of the asthenic syndrome had certain stages depending on duration and severity of emotional, vegetative, dissomnic and other psychosomatic disorders. It was shown that, being one of the key integral indices of human adaptability, psychic performance retained on sufficiently high level for a long period during asthenic syndrome. PMID- 1297496 TI - [The Incubator-2 unit for the study of the embryonic and postembryonic development of birds in weightlessness]. PMID- 1297497 TI - [The protein composition of the blood plasma of cosmonauts after prolonged orbital flights]. AB - The method of two-dimensional electrophoresis was used to determine the protein composition of blood plasma in the cosmonauts stayed on board Mir station over 166 and 366 days. Separation pattern of plasma protein observed next day after landing had several typical differences from the standard pattern of plasmatic proteins found during a preflight examination and on the 7th postflight day. The changes were an increase in intensity of specific protein spots as well as in occurrence of unusual protein spots. PMID- 1297498 TI - [The blood serum peroxidase activity of those working with video display terminals]. PMID- 1297500 TI - [The effectiveness of using repeated hypoxic-hypercapnic stimuli for enhancing cardiorespiratory reserves in exposure to radial accelerations]. PMID- 1297499 TI - [Video display terminals: their electromagnetic safety]. AB - Widespread application of video terminals (VT) has led to accumulating some unambiguous data on harmful effect of electromagnetic and electrical fields on the health. An analysis indicates that the level of electromagnetic and electrical fields is below permissible limits. IRPA/INIC concludes that the electromagnetic effects on VT users health are unharmful. However, the problem of VT use is an integrated one and involves not only radiation but ergonomic aspects and in this context requires further studies. PMID- 1297501 TI - [Autorosette formation in the peripheral blood of subjects under a long-term limitation of motor activity]. PMID- 1297503 TI - [A new scientific and social organization--the K. E. Tsiolkovskii Academy of Cosmonautics]. PMID- 1297502 TI - [The righting reaction in free fall in labyrinthectomized rats after a flight on the Kosmos-936 biosatellite]. AB - The paper presents the experimental data on a turning over reaction in labyrinthectomized rats after 18.5 day flight on Cosmos 936. On Earth, the labyrinthectomized rats are found to exhibit with time an activation of gaze fixation reflex (GFR) which substitutes for labyrinth function when executed a turning over reaction. In microgravity, in the labyrinthectomized rats there is no activation of GFR and postflight turning over reaction is absent in the rats. PMID- 1297504 TI - [The 40th anniversary of the start of aviation physician training in the Military Medical Department of Saratov Medical Institute]. PMID- 1297505 TI - Recent pathogenic concepts of primary open angle glaucoma and soft glaucoma (POAG). AB - Loss of mainly field in POAG is due to Schnabel's cavernous atrophy of the axons at their scleral passage, built up by aligned stacks of glial collagen (IV and I) tissue plates, which contain capillaries. Organisation, size and structural surroundings encircle isolated or grouped axons not evenly distributed. The stereotype pattern of fieldloss linked to a characteristic optic nerve lesion suggests POAG be considered a N.O. disease as raised IOP may be only one of the risk factors. Are cavernous atrophy (loss of field) and the trabecular spaces narrowing (rise of IOP) both the result of the same pathogenic mechanism acting on the collagen fiber (IV and I) of the scleral coat, resp. lamina cribrosa (posterior segment) and trabecular meshwork (anterior segment)? If so, IOP-rise only worsens the condition as will do a hemodynamic energy crisis at the level of the axons. Interactive dominance at any of both levels may explain unexpected discrepancies between IOP and fieldloss. Considering "to treat or not to treat" accurate field loss predictability testing, urgent research topic, are discussed. PMID- 1297507 TI - Psychophysical mechanisms and treatment of vasospastic disorders in normal tension glaucoma. AB - Vasospasms are inappropriate constrictions of small vessels leading to a variety of clinical pictures depending on the location of such spasms. Although the pathophysiological mechanism is not yet well understood, we know some factors able to provoke spasm in patients with appropriate predisposition like hemorrhage, coldness, emotional stress and others. Such vasoconstrictions provoke normally relative mild symptoms like cold fingers, or pain as in variant angina and in only very rare cases, to irreversible structural damage such as myocardial infarction. There is not much known about the involvement of the eye in vasospastic disorders. Retinal migraine is a known entity but occurs quite seldom. If one looks for it, one can often find (mostly reversible) visual field damage in patients with vasospastic disorders. This might be a sign of a reversible functional damage most probably due to a decreased circulation in the optic nerve head or the surrounding choroid. In most of these patients the optic nerve head looks normal, sometimes slightly pale. In patients with the so-called normal-tension glaucoma however, the prevalence of vasospastic disorders, is very clearly increased. This leads to the hypothesis that recurrent vasospasm in the eye may, in some cases, finally lead to structural damage, presenting itself phenomenologically as normal-tension glaucoma. Therefore treatment or selected normal tension glaucoma patients with calcium-channel-blockers is helpful, as has been proven in prospective studies. PMID- 1297506 TI - Diagnosis and long term follow up of glaucomatous visual field defects with automated perimetry. AB - Automated perimetry has added a very important standardized observation post to the clinician's perspective on glaucoma. This paper reviews the major characteristics of field loss in glaucoma as detected with automated perimetry. Practical problem cases are used to illustrate and emphasize specific areas of interpretation difficulties. PMID- 1297508 TI - Indications for trabeculectomy in open angle glaucoma. AB - Trabeculectomy is the most commonly performed filtering procedure in the surgical treatment of open angle glaucoma. One may oversimplify and state that a trabeculectomy is indicated in a case of uncontrolled IOP on maximum tolerated medical therapy in the presence of significant optic disk and/or visual field changes. However, before one actually proposes a trabeculectomy one must consider for a given patient: How does one define IOP control? What are the chances of success of the surgery? What are the operative risks? What are the risks of not operating for the case under consideration? And more generally: What are the arguments of earlier surgery? Where does Argon Laser Trabeculoplasty fit into the therapeutic regimen? The questions are examined with the specific goal of making a rational decision for the patient at hand. PMID- 1297509 TI - Antimetabolites in the surgical treatment of glaucomas. AB - Fibroblast proliferation with scarring at the surgical site plays an important role in the failure of filtration surgery. Several antimetabolites inhibit fibroblast proliferation in vitro. These observations have lead to the widespread clinical use in humans of 5-fluorouracil and more recently mitomycin-C in glaucoma filtering surgery. PMID- 1297510 TI - Cyclocryotherapy as an alternative treatment for primary glaucoma. AB - Cyclocryotherapy was used as an alternative treatment for primary glaucoma in a series of 56 patients, both with narrow and open angle. In this prospective study treatment was successful in 87.7% of the cases (Peak I.O.P. < or = 20 mm Hg) with a mean follow up period of 10.1 months. Mean intraocular tension decreased from 29.7 mm Hg preoperatively down to 17.25 mm Hg postoperatively. About 60% of the eyes, however, needed an additional local treatment. Postoperative complications were rare and mild. A conjunctival congestion, and a mild self limiting iridocyclitis, were the most frequent ones. Long term efficacy was evaluated retrospectively (21 eyes with primary glaucoma; mean follow up period: 51 months). 58.3% were still controlled today, the majority of them requiring local medication. A further deterioration of visual field, however, had been noticed in 26.6% of these "obviously normotensive eyes". Because of its good efficacy and its lack of severe complications as opposed to trabeculectomy cyclocryotherapy is suggested as a first choice treatment in primary glaucoma. PMID- 1297511 TI - [Hemo-rheology of glaucomatous neuropathy]. AB - The vascular participation to the optic nerve pathogenesis has been contradicted. The red blood cell velocity in the optic nerve capillary with a laser Doppler velocimeter, an atraumatic and reliable method, and the aggregability was determined with an erythroaggregameter to know whether an erythrocyte hyperaggregability could slow down the optic nerve blood flow as it has been previously demonstrated in an experimental study. The experiment on the open angle glaucoma patients showed that their optic nerve blood flow was reduced, and their erythrocyte aggregability significantly increased. The two parameters were not significantly correlated, certainly because of a local papillary autoregulation and of the papilla vessels variability, those two factors could modulate the blood flow response to blood qualitative changes. The erythrocyte hyperaggregability could be explained by erythrocyte membrane modifications that could agree with the glaucoma heredity. PMID- 1297512 TI - Laser cyclocoagulation. AB - Since its introduction in 1973 by Beckman and Sugar, cycloablation, using Nd: YAG laser energy has gained increasing attention. Nd: YAG laser energy may both be delivered in the contact and non-contact mode and the energy source may both work in the pulsed or cw mode. The physical and clinical effects of the various design principles differ. A short survey of the present state of the art is presented. PMID- 1297513 TI - Therapeutic ultrasound for the treatment of glaucoma. AB - We present a summary of the results obtained on 1142 treatments of 1072 eyes treated in our hospital during the last 5 years. Ultrasound has been used to treat 843 eyes with refractory glaucoma and also to restore failed trabeculectomy filtering blebs in 229 eyes. The single treatment success rate with success defined as an IOP > or = 20 mm Hg was 59% at one year and 46% at 3 years. In cases of failed blebs, ultrasound treatment performed 3 to 12 weeks after trabeculectomy revived the blebs of 82% of the phakic eyes when 5 FU subconjunctival injections were performed in the following days. PMID- 1297514 TI - Holmium laser sclerostomy in glaucoma management: a new tool for an old procedure. AB - A THC: YAG laser (thulium, holmium, chromium doped YAG crystal) was used to create thermal sclerostomies in 49 glaucomatous eyes of 46 patients. The laser is a long-pulsed (300 microseconds), compact, self contained, solid state laser operating in the near infrared (2.1 mu). A 1 mm conjunctival stab incision was made 12 mm away from the sclerostomy site to allow entry of a specially designed 22-gauge (712 mu) optic probe that delivers energy at a right angle to the long axis of the fiber. Probe insertion produced minimal disturbance of the conjunctiva. Pulse energies of 80 mJ tot 120 mJ were used with a repetition rate of 5 pulses/sec. Total energy levels to produce full-thickness sclerostomies ranged from 1.4 to 7.2 J. Subconjunctival 5-fluorouracil injections were administered in 46 eyes. Estimated probability of success was 74% at 6 months and 67% at 12 months. Mean intraocular pressure of successful cases was 13.3 mmHg at both both 6 months & 12 months. Twelve cases failed within the initial 6 months, and two additional cases failed by 12 months. PMID- 1297515 TI - Structural changes of the lamina cribrosa and of the trabeculum in primary open angle glaucoma (POAG). PMID- 1297516 TI - Morphological aspects of normal optic disc and early signs of glaucomatous alterations. AB - A group of 110 eyes with untreated ocular hypertension, 94 being non-exfoliative and 16 exfoliative and in addition 10 glaucomatous eyes were selected for this study. The optic nerve head was examined by ophthalmoscopy and a drawing was made of the estimated cupping. The disc pallor was measured from disc photographs in a double masked manner at the same time. The possibility to detect early glaucomatous damage by a single examination will be discussed and the two methods will be compared. This study indicates that an increasing vertical diameter of disc pallor might have a predictive value. PMID- 1297517 TI - Biomorphometry and histomorphometry of the optic disc with special reference to the parapapillary region. AB - Glaucomatous optic nerve damage is typically associated with intrapapillary changes such as neuroretinal rim loss. In this study, parapapillary chorioretinal atrophy was evaluated in 691 normal eyes, 1081 glaucomatous eyes and 31 eyes with ocular hypertension. It was significantly larger and occurred more often in the glaucomatous eyes (parapapillary atrophy area: 1.07 +/- 0.83 mm2) than in the normal eyes (0.55 +/- 0.64 mm2) or the eyes with ocular hypertension (0.55 +/- 0.37 mm2). These differences were significant also for eyes with moderate glaucomatous damage (0.86 +/- 0.62 mm2). Parapapillary chorioretinal atrophy was associated with shallow glaucomatous cupping, diffuse nerve fiber loss, markedly tessellated fundus and only moderately elevated intraocular pressure. It increased with decreasing neuroretinal rim area. It showed a spatial correlation to neuroretinal loss inside the optic disc. In unilateral glaucoma, it was larger in the affected eye than in the unaffected eye. Differentiated into zones Alpha and Beta, it correlated clinico-histologically with a complete loss of retinal pigment epithelium cells and incomplete loss of photoreceptors (Zone Beta) and pigmentary and structural irregularities of the retinal pigment epithelium (zone Alpha). Parapapillary chorioretinal atrophy is associated with glaucoma. PMID- 1297518 TI - Measurement of retinal nerve fiber layer thickness and its functional correlations with the visual field. AB - We have developed a technique for stereophotogrammetric measurements of retinal nerve fiber layer thickness at the disc margin. This technique has a reproducibility ranging from 3.9% to 6.0% in normal, ocular hypertensive and high pressure open angle glaucomatous eyes. The presence of a halo or scleral crescent had no effect on the reproducibility of the measurements. The measurements have shown that ocular hypertensive eyes have about an 18% decrease of retinal nerve fiber layer thickness compared to normals. High pressure open angle glaucomatous eyes have about a 43% decrease in retinal nerve fiber layer thickness compared to normals. This technique allows the development of maps of retinal nerve fiber layer thickness so that localized changes at the disc margin can be detected. The thinnest nerve fiber layer occurs primarily in the temporal segment. This technique has also correlated measurements of nerve fiber layer thickness with other measurements of the optic disc, particularly showing a significant correlation with area of pallor as well as measurements of the width of optic disc cup at about halfway between surface and the bottom of the cup. A significant correlation with visual field loss has been shown in high pressure open angle glaucomatous eyes, primarily with the temporal quadrant of the retinal nerve fiber layer and the nasal visual field. The rate of the visual field change in primary open angle glaucoma has been correlated with the initial nerve fiber layer thickness, with the greater the retinal nerve fiber layer thickness the greater the rate of the visual field loss during follow-up. These findings suggest that retinal nerve fiber layer thickness discriminates between normal, ocular hypertensive eyes as well as those with open angle glaucomas and may be useful in following patients with open angle glaucoma prior to development of the visual field loss. PMID- 1297519 TI - Color vision and contrast sensitivity tests in early diagnosis of primary open angle glaucoma. AB - Color vision was examined by the Farnsworth 100 hue test in 48 eyes with ocular hypertension (OHT). Thirteen eyes had a general loss of color discrimination and 8 had a blue-yellow axis. Spatial contrast sensitivity was tested in 31 eyes with OHT by the Mentor B-VAT and was reduced in 8 of them. Temporal contrast sensitivity was explored in 40 eyes with OHT by the Flickersyst&m and showed abnormal responses in 11 eyes. According to the lack of specificity of the responses and the overlapping of the results of normal eyes and OHT eyes, those tests are not useful for classifying an individual patient. Such investigations however have the interest to show that macular mediated functions may be impaired early in glaucoma. PMID- 1297520 TI - Contribution of pattern electroretinogram and pattern visual evoked potential in early diagnosis of primary open angle glaucoma. AB - Pattern electroretinogram (PERG) combined with visual evoked potential (VEP) has become increasingly useful in clinical assessment of the anterior visual pathways. In regard to the PERG dependence on ganglion cell activity, we studied monocular PERG in 36 patients (71 eyes) with intraocular hypertension (6 eyes under topical beta-blockers) and in 10 patients (18 eyes) with advanced glaucoma, to estimate the potential effect of increased IOP on ganglion cells. We recorded simultaneous VEP to evaluate the retino-cortical conduction time. Referring to normal values obtained from 19 eyes (12 subjects), we found clear-cut PERG abnormalities in 20 eyes among ocular hypertensive patients with increased IOP. They were more altered in the advanced glaucomatous group. Two or three control exams were performed in 10 patients every 6 months: however such a short-time follow-up seems too limited to define the ERG prognosis value in this pathology. Comparing the PERG with the clinical routine assessments, we discuss its place in the diagnosis and in the follow-up of patients with ocular hypertension. PMID- 1297521 TI - [Psycho-functional and objective tests applied to early diagnosis of POAG, indications for general ophthalmologists and therapeutic incidences]. AB - The early diagnostic of glaucoma (before the appearance of visual field defects) can be made in some cases with the help of certain objective tests and, to a lesser degree, with subjective or psychophysical tests. Retinal nerve fiber layer photography is certainly the most rewarding objective test, providing the technique has been mastered and there is a clear fundus view without chorio retinal atrophy. The identification of nerve fiber defects is an almost sure sign of glaucomatous damage in the absence of other pathology. An abnormally small neuroretinal rim area can also be an indicator of glaucoma. However, no conclusion can be drawn if the value is within the wide range of normal limits. Electrophysiological tests in glaucoma patients at the present time give results that show too much variability and overlap with those of normals to be of practical value. The same can be said for subjective tests such as spatial and temporal contrast sensitivity (the flicker test, for example). The specificity and sensitivity of the tests are too weak to be useful for the diagnosis of glaucoma in 1992. PMID- 1297522 TI - [Importance of the role of dose rate on tumor induction in rats after radon inhalation]. AB - Lung cancer can be induced in rats, by radon daughter products, after exposure as low as 25 WLM (80 mJ.h.m-3) protracted over 4 to 6 months with a dose rate of 100 to 150 WL (2 to 3 mJ.m-3). The incidence of lung cancer is not increased and is equal to that of controls when the same cumulated dose is protracted over 18 months at 2 WL (0.042 mJ.m-3). PMID- 1297523 TI - Evolutionarily conserved promoter motifs and enhancer organization in the mouse gene encoding the IIB myosin heavy chain isoform expressed in adult fast skeletal muscle. AB - We have isolated the mouse gene for the MHC isoform expressed in adult type IIB (fast-contracting, glycolytic) skeletal muscle fibers, and determined the DNA sequence of the promoter region. This sequence represents the first example of a promoter for a gene encoding an adult-specific isoform of a mammalian skeletal MHC. The proximal 200 bp of the promoter contains several sequence motifs which are identical or very similar to homologous motifs found in the promoters of a family of chicken skeletal MHC genes. Of these, two novel AT-rich sequences may be important for regulation of the promoter. A second feature of the mouse IIB MHC promoter sequence concerns a number of sequence motifs located at ca. -1,000 bp which are organized in a similar fashion in the IIB MHC promoter and a homologous region of promoter of the mouse muscle creatine kinase gene. PMID- 1297524 TI - [Effect of elastin peptides on cell proliferation]. AB - Elastin peptides were shown to act on a cell membrane receptor coupled to a G protein, phospholipase C, and its activation increases IP3 and DAG and opens receptor-dependent Ca(++)-channels. As some growth factors also produce similar modifications in intracellular Ca++, we wanted to explore the effect of elastin peptides on cell proliferation using 3H-thymidine incorporation and cell counting. The concentration of peptides needed for the stimulation of cell proliferation varied between large limits (1 microgram/ml to 10 mg/ml) according to the origin of the cells and the nature of the peptides. The proliferation of CCL 39 chinese hamster lung fibroblasts was enhanced in a dose-dependent fashion in the concentration range of 3 to 10 mg/ml. The proliferation of human skin fibroblasts was enhanced in the concentration range of 0.5 to 3.3 mg/ml and inhibited at higher concentrations. This effect depended little on the average molecular weight (MW) of the peptide preparation, high MW peptides (average 75 kDa) and lower MW peptides (average MW 10 kDa) were both efficient approximately to the same extent. It appears probable that only a small fraction of these peptides possesses this growth promoting property; other sequences might have the opposite effect. The conformation of the peptides may also play an important role. Human sera contain circulating elastin peptides in the concentration range of 1.0 to 10 micrograms/ml, increasing in obstructive arteriopathies and in some hyperlipidemias. It appears therefore that the above findings may have physiopathological significance in the regulation of cell proliferation in normal and pathological conditions. PMID- 1297526 TI - [Lethal effect of boron neutron capture reaction on human uveal melanoma cells in culture incubated with borophenylalanine]. AB - Cell cultures obtained from human uveal tumours have been used as experimental model to study the lethal effect consecutive to the neutron capture reaction on boron incorporated into cells as borophenylalanine. An irradiation with a neutron fluence of 6 x 10(9) n cm-2 reduced the number of viable cells by about 30%. PMID- 1297525 TI - Early detection of heart transplant rejection using cardiac echography combined with the assay of glycosylated residues in plasma by proton NMR spectroscopy. AB - Early diagnosis of acute cardiac graft rejection by non-invasive methods is required for medical, organizational, psychological and economic reasons. We have monitored 18 heart recipients over a period of 2.5 years using endomyocardial biopsies (EMB), cardiac Doppler-echography (CDE) and proton NMR spectroscopy assay of plasma glycosylated residues. Diastolic parameters of CDE and assay of the glycosylated residues by NMR spectroscopy respectively detect 42 and 45% of the acute low grade (mild or moderate) histological rejections. The combination of the two methods allows the detection of 65% of rejections. The strategy combining plasma NMR spectroscopy and echography is pertinent to the non-invasive detection of acute cardiac rejections with low histological grade. PMID- 1297527 TI - [Description of cell line established from human thyroid papillary cancer and secreting human chorionic gonadotropin hormone]. AB - One of the difficulties in characterization of the oncogenes involved in thyroid carcinogenesis is the production of cell lines. Arising from a poorly differentiated thyroid papillary carcinoma we have established a cell line synthesizing the thyroglobulin and human chorionic gonadotropin (alpha and beta subunits) (HCG) hormones. These cells will allow research of the oncogenes involved or potentially involved in thyroid papillary carcinomas and evaluation of the role of the autocrine secretion of HCG. PMID- 1297528 TI - [Study of the role of negative regulator, AcSer-Asp-Lys-Pro (AcSDKP) in the phenomena of cellular proliferation]. AB - The intra and extracellular kinetics of AcSDKP levels in cell culture have been studied. A close correlation was observed between the minimal level of intracellular AcSDKP (a negative regulator of cell proliferation) and the initiation of DNA synthesis. The return to initial levels of intracellular AcSDKP when the rate of DNA synthesis decreases, suggests a role for the tetrapeptide in homeostasis during cell growth. The return to normal values was not observed in preliminary studies on cell lineages during uncontrolled proliferation. PMID- 1297529 TI - Nucleus reticularis thalami participates in sleep spindles, not in beta rhythms concomitant with attention in cat. AB - In the awake cat, characteristic electrocortical synchronized oscillations (beta rhythms) can develop on the parietal cortex in specific behavioural situations such as during attentive fixation of a target. These activities differ from other synchronized rhythms which accompany slow sleep ("spindles") and are more widespread. It is shown here through single unit recording from the thalamic nucleus reticularis (RET), that the latter structure participates in spindles (as already postulated by other authors), but not in the beta rhythms which seem to depend on a more restricted thalamic focus in the posterior thalamic nucleus. These data thus support the idea that RET plays a role in slow-wave sleep but not in the cognitive operations involved in focussing attention. PMID- 1297530 TI - [The quality of anesthesia-induced sleep and memory]. PMID- 1297531 TI - [Sequential analgesia. Technical aspects]. AB - Combined spinal and epidural anaesthesia was described by P. Moulaert. After searching the epidural space, a spinal needle is introduced through the Tuohy needle for performing the intrathecal block; then an epidural catheter is put for the postoperative analgesia. The author from his own experience of this regional anaesthesia proposes modifications of the Tuohy and spinal needles to improve the technique. PMID- 1297532 TI - [Does the differential block by the epidural route provide a diagnostic aid in chronic pain?]. AB - Sixty-two patients with chronic pain below the waist level were evaluated with a differential epidural block performed after an overall somatic and psychological assessment. The pain and neurophysiologic variations under block were compared with the somatic and psychological findings. No consistent relationship was found between pain variations and sympathetic sensory effects of the graduated epidural block. The presence of neurological diseases and depressive or hysterical disorders influenced particularly the pain responses to the block. It is concluded that the differential epidural block is not sufficient to affirm the somatic origin of a chronic pain and must be always confronted with the somatic and psychosocial findings. PMID- 1297533 TI - [Evolution of the blood levels of propofol administered by continuous perfusion during extracorporeal circulation]. AB - The pharmacokinetics of propofol administered in continuous infusion was studied in 10 patients without left ventricular insufficiency during extracorporeal circulation (ECC) with hemodilution, for aortocoronary bypass. After a dosage of 1.5 mg.kg-1 during anaesthetic induction, the blood level was 4,800 micrograms.l 1. Under continuous infusion levels remained very high: they decreased by 40% during EEC induction and rose more than 10% when artificial ventilation started again. These modifications can be explained by physiological variations induced by EEC (non pulsated flow, redistribution, vasoconstriction, hemodilution, hypothermia) and they lead to adapt dosages in this type of anaesthesia. PMID- 1297534 TI - [Tracheal rupture following general anesthesia]. PMID- 1297535 TI - [Secondary migration of a central venous catheter linked to an implantable port]. AB - The secondary migration of the distal part of a central venous catheter with implantable port is rarely described. This study reports a case in which the distal part of a catheter with implantable port moved spontaneously, a month after its implantation in a branch of the internal jugular vein without any other complication. The discussion is about modalities, frequency and explanation mechanisms of the complications due to central catheters. The conclusion insists on systematical radiologic control of the position of implantable port with central venous access, and in case of bad working or any sign of thrombo phlebitis. PMID- 1297537 TI - [The Heart Institute, Ho Chi Minh City: evaluation of the first 100 patients]. PMID- 1297536 TI - [A fatal gas embolism during a hysteroscopy-curettage]. AB - A 26 year old woman without any pathological history except metrorrhagia underwent a hysteroscopy under epidural anaesthesia and uterine cavity dilatation by saline solution. A respiratory distress and cardoffirculatory arrest occurred at the end of the procedure. Despite several attempts of cardiorespiratory resuscitation the patient deceased. The diagnosis retained was a gas embolism caused by blast effect from reintroduction of the hysteroscope into the uterine cavity. Different mandatory security measures are evoked. PMID- 1297538 TI - [Anesthesia and the recruitment of patients]. PMID- 1297539 TI - [Accusation of collective rape: role of propofol?]. PMID- 1297540 TI - [Fresh frozen plasma with reduced risk. French Blood Agency]. PMID- 1297542 TI - [Demographic projection of the health occupations and prospectives of the health system (1962-92)]. PMID- 1297541 TI - [The health system during the next 20 years]. PMID- 1297543 TI - The health system and policy in Bulgaria: problems and trends. PMID- 1297544 TI - [General practitioners' experience in a mass screening campaign of colorectal cancers]. AB - In a mass screening campaign of colorectal cancer, general practitioners play an essential role for obtaining a high rate of participation from people. It is important to analyze the reasons for the participation and their actual experiences in the campaign. Out of 71 GPs participating in the campaign, 67 have been interviewed by a sociologist and 51 GPs (76%) considered themselves "motivated" for participating after an instruction course in small groups. Sixteen GPs were sceptical about the outcome or not highly motivated. However thirteen of them participated by moral obligation vis a vis their patients or for not being different from their colleagues. All GPs appreciated being actively involved in the organization of the screening campaign and considered that the public had been well informed. Such information covered the information leaflet, the press campaign at the beginning of the campaign and the recall letter for those who had not been consulted during the time when the test was distributed by GPs. The main constraint was the time spent to convince the patients to do the screening test and explain its importance. The additional time, 5 to 10 minutes per consultation was important to the GPs. They thought it was fair to be paid for their active participation. These data suggest that it is possible to motivate GPs for a mass screening campaign, on the condition that they are actively involved and participate in an instruction course for small groups. PMID- 1297545 TI - Industrialization, ambient air pollution, and death from respiratory disease and respiratory cancer in the northeastern United States. PMID- 1297546 TI - [Analysis of different aspects of the health systems in Tunisia]. AB - The health care system in Tunisia is composed of two sectors, public and private. Given the social and economic development level of the country, it can be said that the hospitals, health centers and workforce devoted to health are not severely limited. However, these structures are under-equipped and finance management is not relevant. The establishment of a National Health Service would render all the system more efficient. PMID- 1297547 TI - [Aggravation of hypoxemia in supine position in myotonic dystrophy]. AB - Myotonic dystrophy (MyD) involves a variety of systems. Respiratory disorders are common, namely elevation of diaphragm, alveolar hypoventilation, aspiration pneumonia and sleep apnea. We evaluated respiratory involvement. The subjects were 11 patients with MyD. Also 6 patients with limb girdle muscular dystrophy (LG) were examined to be compared with MyD. Both groups had the similar activities of daily living. All of them never complained of dyspnea. Arterial blood gas studies were performed in supine position and standing position. A new evidence was found that hypoxemia was aggravated and alveolar-arterial oxygen pressure difference was increased in supine position in MyD. Next, pulmonary function tests were done in supine position and sitting position. Functional residual capacity (FRC) were more reduced in supine position in MyD compared with LG. The value to subtract closing capacity from FRC was negative in supine position in MyD, showing closing phenomenon. We propose the mechanism of the aggravation of hypoxemia may be the following. The reduction of FRC caused by respiratory muscle involvement brings out the closing phenomenon. Abnormal uneven distribution of ventilation-perfusion ratio happens and then hypoxemia is worsened in supine position in MyD. PMID- 1297548 TI - [X-ray computed tomographic scans of lower limb and trunk muscles in facioscapulohumeral muscular dystrophy]. AB - X-rays computed tomographic (CT) scans of muscles of the lower limbs and the trunk in 14 patients with facioscapulohumeral muscular dystrophy (FSH) were studied. The CT scans showed that the affected muscles were decreased in density and size. The laterality of muscular involvement was sometimes observed. The muscular lesions in the lower limbs showed proximal distribution. In the thigh, the hamstrings were affected first, the adductor muscles second, and then the muscular involvement progressed to the quadriceps femoris muscle. In the lower leg, the gastrocnemius and soleus muscles were relatively spared as compared with the tibialis anterior muscle. In the lumbar girdle, the abdominal muscles were involved first, the gluteal muscles second, the back muscles third, and the psoas major muscle were relatively spared. The muscular weakness of this distribution exacerbated lumbar lordosis. The neck muscles were less affected than those of the lumbar girdle. The CT scans in FSH demonstrated the characteristic pattern of muscular involvement, which differed from the inherited muscular diseases such as Duchenne muscular dystrophy, myotonic dystrophy, and others. PMID- 1297549 TI - [A hereditary ataxia associated with hypoalbuminemia and hyperlipidemia--a variant form of Friedreich's disease or a new clinical entity?]. AB - The patients belonged to three different families and were products of consanguineous marriage. The neurological symptoms and signs in these patients began in infancy or childhood and included gait disturbance, horizontal nystagmus, distention tremor of the hands, muscular wasting and sensory impairment of the hands and legs. CT-scan and/or MRI showed atrophy of the cerebellum. Serum biochemical analyses revealed hypoalbuminemia with hyperlipidemia. There were no abnormalities in the heart, liver, kidney, gastrointestinal tract, or endocrine systems. The autopsy revealed degenerative changes in the spinal cord including posterior column and lateral pyramidal tract, as well as in the peripheral nerves and cerebellar cortex. Although we have speculated that the disease presented here would be a clinical variants of Friedreich's disease, it would make a new clinical entity because there was no report about the association to hypoalbuminemia and hyperlipidemia with spinocerebellar degeneration. PMID- 1297550 TI - [Antibodies to GM1 ganglioside in motor neuron disease--in comparison with demyelinating neuropathy]. AB - We studied serum antibodies to GM1 ganglioside by enzyme linked immunosorbent assay (ELISA) in 55 patients with motor neuron disease (MND) composed of 36 ALS and 19 lower motor neuron disease (LMND), 44 patients with demyelinating neuropathy (DN) composed of 29 Guillain-Barre syndrome (GBS) and 15 chronic inflammatory demyelinating polyneuropathy (CIDP), and 21 healthy controls. High levels of serum antibodies against GM1 were confirmed by thin-layer chromatography overlay procedure. In MND group, the mean level of anti-GM1 IgM antibodies was not significantly elevated in comparison with controls. There was no significant difference in anti-GM1 antibodies between ALS group and LMND group, while anti-GM1 IgM antibodies in DN group, especially in GBS group, were significantly elevated (p < 0.001). High levels of anti-GM1 IgM antibodies (greater than the mean level plus 3 standard deviations of controls) were detected in 9 patients (6 with ALS and 3 with LMND) with MND (16.4%) and 16 patients (11 with GBS and 5 with CIDP) with DN (36.4%). Serum antibodies to GM1 reacted with GD1b ganglioside in only one patient with MND and 10 patients (8 with GBS and 2 with CIDP) with DN. Anti-GM1 IgG antibodies were elevated significantly in DN group. There was no correlation among anti-GM1 IgM antibodies and both duration and severity of illness in MND. In some patients with MND, levels of anti-GM1 IgM antibodies became high in the advanced stage. It is unclear whether these antibodies are primary manifestation or consequence of motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297551 TI - [Clinical significance of carotid and ocular bruits in cerebrovascular disease]. AB - We investigated the clinical significance of carotid and ocular bruits in 250 consecutive patients with cerebrovascular disease (CVD). The incidence of bruits was compared with that in 100 age- and sex-matched neurological controls without CVD. In the cerebrovascular disease group, carotid bruits alone were found in 12 patients, both carotid and ocular bruits in 7, and ocular bruits alone in 2. Carotid bruits were found only in 3 controls. We then evaluated cerebrovascular disease in the 25 patients (16 men and 9 women) who had bruits. The patients ranged from 55 to 81 years in age (mean: 70.6 years). The patients with carotid bruits alone constituted the largest group, and those with ocular bruits alone were the smallest group. Carotid bruits were heard and abnormal blood flow was observed in 19/28 arteries of the 21 patients who underwent echo-flow studies. Carotid artery stenosis/occlusion was detected in 24/31 arteries (77%) in 23 patients who underwent digital subtraction angiography (DSA). Thus, the sensitivity was 0.77 and specificity of a carotid bruit 0.91, respectively. In 9/10 patients with unilateral ocular bruits, ipsilateral or contralateral carotid artery stenosis/occlusion was detected. Diminished cerebral blood flow was observed in 10/15 patients with bruits who underwent SPECT. Of these 8 had reduced cerebral blood flow ipsilaterally to the bruit. Blood flow was reduced in the carotid artery territory in all of the patients, and watershed reductions were commonest. Among the 25 patients, some showed neurological semiology of the vertebrobasilar territory in addition to that of the carotid territory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297552 TI - [Gene expression in lactate dehydrogenase-A subunit deficiency]. AB - A 33-year-old female complained of muscle pain and stiffness after severe exercise from the age of nine. Her sister also had similar symptoms. Consanguinity was found in her parents. Neither muscle wasting nor weakness was detectable. The activity of LDH in the muscle was decreased less to than 8% of normal value. The isoenzyme pattern of the muscle LDH revealed only one band of B4. The levels of blood lactate did not rise on anaerobic exercise, while a marked increase of pyruvate was found. Northern blot analysis showed that the ratio of LDH-A transcript to beta-actin transcript in the patient was similar to that in a normal subject. RNA preparations were reverse-transcribed, amplified by a polymerase chain reaction (PCR), and separated by electrophoresis. The size of PCR product corresponding to exon 6 was decreased. The nucleotide sequence of this product was determined and a 20 bp deletion was found. This mutation results in a frame-shift translation and premature termination. The predicted incomplete LDH-A subunit contains only 259 instead of 331 amino acids. Immunofluorescence for LDH-A subunit could be seen within the cytoplasm and on the surface membrane of the muscle fibers in our patient as well as control subjects by the immunohistochemical studies. These findings suggest that LDH-A mRNA is transcribed in a truncated form and an enzymatically inactive protein is produced in the patient's muscles. PMID- 1297553 TI - [Widespread tau abnormality in a case of cortico-basal degeneration]. AB - A case with cortico-basal degeneration was reported with special reference to the immunohistochemical study. A 59-year-old housewife noted tremor and clumsiness of her left hand. On the initial examination she showed the hyperreflexia of the upper extremities and jaw jerk, parkinsonian symptoms such as Myerson sign, parkinsonian gait and rigidity in the left arm. She showed pronounced forced grasping in the left hand. At the age of 60 she showed a WAIS scale with verbal IQ of 99 and performance below the scale. She could not copy hand postures. Tremor was aggravated by action or anxiety, more prominent on the left hand. There was some incoordination on the finger-nose testing of left arm and on the knee-heel testing of both legs. She also showed homolateral dyskinesia. She had a left Babinski sign and sensory testing was normal. A CT scan showed slightly enlarged ventricles (Fig. 1). At the age of 61 she could not understand simple requests and speak few words spontaneously, showing severe dysarthria. There were palilalia and motor impersistence. CT scan showed more widening of the lateral ventricles. At the age of 62, she had lingual dyskinesia and tapping on her upper lip provoked myoclonic jerk on her arms. She died of pneumonia at the age of 65 years, 6 years from the onset. The brain weighed 1190 g. There were bilateral old subdural hematomas on the right parietal and occipital lobe and the left parietal lobe. There was atrophy of frontal and superior parietal region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297554 TI - [A cervical collar therapy for non-progressive juvenile spinal muscular atrophy of the distal upper limb (Hirayama's disease)]. AB - Non-progressive juvenile spinal muscular atrophy of the distal upper limb (Hirayama's disease) occurs predominantly in men in the second decade with unilateral weakness of the fingers and hand, and atrophy of the hand and forearm. The symptoms generally progress for 3-4 years after onset and then stop. Since the second decade is a very important period starting one's career, early stopping of the progression and possibly the improvement are essential. On the bases of the neuroradiological studies, a forward displacement of the posterior wall of the dural canal at the lower cervical level on neck flexion is presumed to be the main pathogenetic mechanism in this disease. On neck flexion, the spinal cord is compressed anteroposteriorly at C7 and C8 segmental levels. Pathological studies suggested that chronic microcirculatory disturbances in the spinal cord as the result of repeated flexion of the neck might produce necrosis of the anterior horns. We used a cervical collar for the prevention of neck flexion in 14 patients in the early stage and compared the results with those of 18 patients who had natural courses. In the therapy group, muscle weakness of the affected hand improved in 5 patients and the progression of the disease was stopped in 8 patients with the duration of 1.8 +/- 1.2 years, whereas the duration of progression of the natural course group was 2.9 +/- 1.6 years. Only one patient who could not tolerate the use of collar showed a slight progression. These results suggest that the cervical collar is a useful therapeutic tool in this disease. PMID- 1297555 TI - [Migrant sensory neuritis--electrophysiological and pathological study]. AB - Migrant sensory neuritis, which was first proposed by Wartenberg, is very uncommon and only a few case reports have ever been published. We described one case of migrant sensory neuritis and discussed the pathogenesis of this disease. A 44-year-old man noticed numbness in the lateral aspect of the dorsum of the left foot in February 1985. Physically, there was hypoesthesia in the region of left sural nerve with positive Tinel's sign. During the next 4 years, pain, tingling sensation or hypoesthesia appeared in the regions of the right superficial radial nerve, right axillary nerve, left intercostal nerve, left lateral plantar nerve, digital nerve of the right second digit, left saphenous nerve, right superficial peroneal nerve, left superficial radial nerve, bilateral ulnar nerves and bilateral median antebrachial cutaneous nerves one after another in a migrating fashion. Tinel's sign was also positive at the right superficial radial nerve. In some occasions, decreased deep tendon reflexes were observed, but there had been no muscle weakness. Some nerves showed complete recovery, but others showed persistent involvement. Some nerves were affected repeatedly. Laboratory examination failed to clarify underlying disease except for mild liver dysfunction. Electrophysiological study showed reduced amplitude of the sensory nerve action potential (SNAP) of right sural nerve, left ulnar nerve, right superficial radial nerve and digital branch of right median nerve with preserved sensory nerve conduction velocity. SNAP of left sural nerve was absent. These findings mean the cause of the sensory disturbance is axonal degeneration rather than segmental demyelination. There were no abnormalities in motor nerve conduction study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297556 TI - [A case of fibromuscular dysplasia presenting with Wallenberg syndrome, and developing a giant aneurysm of the internal carotid artery in the cavernous sinus]. AB - A 25-year-old man developed Wallenberg syndrome (WS). At that time his carotid angiography was normal. When he was 28 years old, he suffered from retinal artery embolism in the left eye. At the age of 30 years, he had an acute onset of abducens nerve palsy in his right eye. The carotid angiography showed a giant aneurysm at the cavernous sinus portion in the right internal carotid artery. At his age of 38, the right oculomotor, trochlear and trigeminal nerves were involved. A vertebral angiography revealed a bead-like formation, and a diagnosis of fibromuscular dysplasia (FMD) was made. An intensive angiographic examination revealed many stenotic or dilated lesions in the carotid, vertebral, coronary, renal, and hepatic arteries. A sural nerve biopsy specimen revealed that the sural vein was involved. In Japan only one case of FMD presenting with WS is known. FMD should be under consideration as an underlying disease, when WS occurred in younger patients with few risk factors. In this patient an angiography revealed no abnormality in the cavernous sinus portion of the internal carotid artery, when he suffered from WS. However, eight years later he was proved to have a giant aneurysm in the cavernous sinus portion. In conclusion, we support the hypothesis that aneurysm may originate from angiographically normal arterial wall in FMD. PMID- 1297557 TI - [Two cases of recurrent optic neuritis (OPN) and acute transverse myelopathy (ATM) with associated anticardiolipin antibodies]. AB - We investigated anticardiolipin antibodies (aCL) by enzyme linked immunosorbent assay with adding aCL-cofactor in two cases of recurrent OPN and ATM patients. These two patients had similar clinical features with ATM and OPN during their clinical courses. They were supposed to be suffered with multiple sclerosis (MS), although cranial MRI was normal and oligoclonal IgG band (OCB) was consistently absent in the cerebrospinal fluid. Positive aCL is suggestive that this disease may be a disorder associated with aCL with different etiology and pathogenesis from other MS patients. Serologic testing for aCL with aCL-cofactor should be warranted for MS patients, especially for those showing OPN and ATM during the clinical course, because in orientals the incidence of ATM and OPN is relatively high among MS. PMID- 1297558 TI - [A case of posterior choroidal artery infarction]. AB - The posterior choroidal artery supplies the lateral geniculate body, the posterior thalamus and the caudate body. Currently, a few cases of infarction in this arterial territory have been reported. This is a case of 59-year-old male, exhibiting left homonymous hemianopsia and left hemiparesis. Clinically it was impossible to make a diagnosis of infarction in this area. We were able to determine that it was a posterolateral choroidal artery infarction rather than an anterior choroidal artery infarction using 1.5 T-magnetic resonance imaging (MRI). The MRI scan clearly disclosed the areas of infarction, which included the lateral geniculate body, the posterior thalamus and the caudate nucleus body. Additionally, cerebral angiography revealed an occluded proximal portion of the right posterior cerebral artery (P2) and a patent right anterior choroidal artery. Anatomically, the areas surrounding the lateral geniculate body are supplied by both the anterior and the posterolateral choroidal arteries. However, the posterolateral choroidal artery infarctions are believed to be rare due to usual dominance of the anterior choroidal artery. Presently, with the use of MRI scanning, these areas can be easily visualized. Therefore, the posterolateral choroidal artery infarction can be diagnosed more easily. It is conceivable that more cases will be accurately diagnosed using this tool. PMID- 1297559 TI - [Multifocal axonal motor neuropathy associated with anti-ganglioside antibodies]. AB - We report a patient with asymmetrical patchy weakness of the limbs, and with autoantibodies against gangliosides GM1, GD1b, asialo GM1. Although electrophysiological studies did not reveal conduction block, treatment with prednisolone resulted in clinical improvement. A 52-year-old man was admitted to Kyoto University Hospital, because of gait disturbance. Neurological examination revealed a patchy distribution of weakness in the limbs. Deep tendon reflex was normal at the right knee, and was depressed at the right biceps. Other deep tendon reflexes were absent. There was a slight decrease in vibratory sensation in the distal portions of the lower extremities. Routine laboratory studies, heavy metal screen, vitamin, cryoglobulin, coproporphyrin and delta-amino levulinic acid in urine, and the protein value of the cerebrospinal fluid were normal. Head and neck MRI, and myelography were normal. Immunofixation electrophoresis showed IgM lambda M-protein in serum. Thin-layer chromatography with immunostaining showed his serum IgM reacted with GM1, GD1b, and asialo GM1. ELISA (Enzyme Linked Immunosorbent Assay) demonstrated high titers of anti GM1, GD1b and low titer of anti asialo GM1. Motor conduction studies showed no demonstrable conduction block, normal conduction velocities and the low amplitudes of CMAP. Sensory conduction studies showed no abnormalities except for slightly decreased amplitude of SNAP in sural nerve. Electromyography showed active denervation in extensor digitorum communis muscle, tibialis anterior muscle and left biceps brachii muscle. Muscle biopsy specimen revealed large and small group atrophy and there was perivascular mononuclear infiltration at one point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297560 TI - [Abulia: a case of cerebral infarction in the bilateral genua of internal capsules]. AB - A patient was presented with an outstanding symptom of abulia due to cerebral infarcts in the bilateral genua of internal capsules. A 53-year-old woman, generally in good health and active, had no contributory medical history except for hypertension. She was well until August 20, 1988, when she was noted to have become taciturn and absent-minded. In the morning, she got up and went to work as usual. Although she worked without trouble, she hardly talked with her colleagues. After getting home from work, she would lie down without doing any housework, and this was continued on the following day. However, she had no physical problems. She was thus admitted to a hospital on August 22. Lethargy and urinary incontinence were apparent for a few days. Thereafter she became awakeful and could take care of herself. She sat on her bed all the time, and could talk normally with her daughter. She was referred subsequently to the Department of Neurology, Hyogo Prefectural Tsukaguchi Hospital on August 30. On examination, the patient was alert, polite and cooperative with no physical abnormalities except for high blood pressure. Neurological examination indicated the patient to be attentive and well-oriented. Cranial nerves and eye movements were normal except for slight anisocoria and sluggish pupils. There were no muscle weakness, extrapyramidal signs, or cerebellar signs. Deep tendon reflexes were normal. Babinski signs and forced grasping were not noted. A neuropsychological study showed the patient not to be demented, aphasic, or apraxic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297561 TI - [Treatment of Guillain-Barre syndrome with "axonal" involvement by plasma exchange]. AB - A 19-year-old man with Guillain-Barre syndrome (GBS), who had been bedridden, dramatically improved after plasma exchange despite electrophysiological evidence of severe axonal damage. We commenced the therapy at 24 days after the onset of illness. Each trial of plasma exchange improved the strength clinically and rapidly increased the amplitude of the compound muscle action potential. Four months later, muscle strength recovered to normal except for mild weakness of the distal limb muscles. The time course of such a prompt recovery precludes axonal regeneration as its underlying mechanism in our patient. We postulate that some humoral factor might have reversibly depressed the axonal excitability, causing clinical symptoms which mimic axonal degeneration. Plasma exchange is a choice of treatment even for patients with GBS showing electrophysiological findings suggestive of axonal involvement. PMID- 1297562 TI - [A case of syringomyelia with proximal dominant muscle weakness and without superficial sensory disturbance]. AB - A 43-year-old woman had noticed muscular weakness in her arms for four years before her admission. Muscle weakness and atrophy were prominent in the bilateral deltoid muscles, but muscular strength was almost unimpaired in the bilateral forearms and intrinsic muscles. There was no sign of sensory impairment except vibratory sensation. EMG revealed neuropathic NMU. X-P of the cervical spine showed enlargement of the spinal canal diameter, and MRI of the spinal cord revealed a large syrinx. On the basis of metrizamide CT and cranial MRI, a diagnosis of syringomyelia with Chiari malformation (type I) was made. Despite the presence of a large syrinx extending from C 1 to Th 11, the only detectable neurological sign was proximal weakness of the upper extremities simulating myopathy. PMID- 1297563 TI - [Paraproteinemia and motor neuron disease]. AB - In some patients, motor neuron disease (MND) is associated with a paraprotein, raising the question that there may be a relationship between MND and monoclonal gammopathy. We analysed the presence of monoclonal immunoglobulin in the serum from 53 patients with MND using immunofixation in cellulose acetate membrane. The incidence of paraproteins in 6 cases (11.3%) of patients with MND exceeds values found with cellulose acetate membrane supports in reported populations (below 1%), even when age was also considered. Monoclonal components were IgG (33%), IgM (33%) and IgA (33%). In six cases, four showed typical changes of amyotrophic lateral sclerosis and other two patients were spinal progressive muscular atrophy (SPMA) in autopsy. No malignancy was detected in all cases. These results corroborate the concept of a probable association between MND and benign monoclonal gammopathy (plasma cell dyscrasia). A patient with SPMA had transient elevation of IgG-GM1 antibodies. Other five patients with M-proteinemia did not show elevated serum anti GM1 antibodies. PMID- 1297564 TI - [Rhythmic skeletal myoclonus without palatal myoclonus]. AB - We reported a case of 89-year-old woman showing rhythmic skeletal myoclonus mainly on the right upper limb. This myoclonus appeared five days after the cerebral infarction. It was seen constantly both at rest and in posture, and decreased during voluntary movement. When the patient was under emotional stress, it spread to the submandibular, neck and trunks of upper limb. During sleep, this movement completely disappeared. There was no myoclonus in palato-pharyngo laryngo-oculo-diaphragmatic muscle group. In the examination of the surface electromyography, the movement was not reciprocal between extensor and flexor muscles, and its cycle was about 3.5 Hz. It was different from the intention tremor because it did not increase during the movement phase on the finger nose test. The examination of MRI revealed a small infarction including right dentate nucleus and right superior cerebellar peduncle, and from which an infarction of the superior cerebellar artery territory was considered. Only a few cases of rhythmic skeletal myoclonus without palatal myoclonus have been reported in the literature. All of these cases had small infarction of the same region as the above case. Their myoclonus began 5 to 15 days after the onset of cerebral infarction. These periods were markedly shorter than that of intention tremor and palatal myoclonus. This fact suggest that the rhythmic skeletal myoclonus has a different mechanism from that of the palatal myoclonus. PMID- 1297565 TI - Neurogenic arthropathy. Differential diagnosis. AB - Neurological affections responsible for secondary arthropathic pathology are: tabes, syringomyelia, diabetes mellitus, congenital insensitivity to pain syndrome, alcoholism, leprosy. Each of the affections shows predilection for specific joints: syringomyelia the shoulder, tabes the hip and knee, diabetes mellitus the foot, congenital insensitivity to pain the lower limb, alcoholism the shoulder and knee. The authors discuss two cases of hip arthropathy in previous dorsal myelic fractures. PMID- 1297566 TI - Pathologic features of neurogenic arthropathy. AB - "Neurotraumatic" and "neurovascular" theories are still debated as a basis for the pathogenesis of neurogenic arthropathy. The observations of pathologic features described in the present study lead to the conclusion that both mechanisms, loss of deep sensation and neurovascular reflex inducing increased blood flow and active bone resorption, may contribute to the development of complete joint disorganization. PMID- 1297567 TI - Radiographic and therapeutic aspects of neurogenic arthropathy. AB - The authors describe the typical radiographic aspects of neurogenic arthropathy based on an examination of 127 cases observed at the Rizzoli Orthopaedic Institute. Surgical indications for the various joints affected are discussed, and the results obtained after treatment are reported. PMID- 1297568 TI - Cellular reactions in hip prosthesis loosening. AB - Based on the results obtained in histological examinations carried out on periprosthetic tissues in a large series of cases of prosthetic hip joint explants, the authors analyze the cellular events that may occur in loosening phenomena as compared to what occurs in the paraphysiological repair process that is observed in the stable prosthesis. Like other authors, they believe that the principal role in the mechanism of loosening is played by macrophages which are recalled in a large number, at times together with multinucleate giant cells, at the bone-implant interface, after micromovements of the prosthesis and the formation of wear particles have occurred. The macrophages would be capable of favoring resorption of the periprosthetic bone tissue, producing areas of osteolysis in which the transmission of the mechanical stress of loading is modified. The ensuing prosthetic instability increases wear phenomena, causes a greater amount of osteolysis, and, in a vicious cycle, loss of the relationship between bone and implant, and, thus, prosthetic loosening. Finally, the authors report a hypothesis on the pathogenesis of the phenomenon, based on which non physiological stress, associated with wear and eventually infection, leads to loosening. PMID- 1297569 TI - Biomechanics of cemented and cementless prostheses. AB - The success of the cemented arthroplasty is due primarily due to excellent initial stability, intimate contact with the prepared bone and the isoelastic properties provided by the cement. In an experimental in vitro study, the initial stability of both the cemented and uncemented femoral components was measured and it was found that they were both very stable in simulated single limb stance (maximum motion of less than fifty microns). However, in simulated stair climbing, the uncemented components were more unstable than the cemented components (maximum micromotion of 76 microns for cemented and 280 microns for uncemented), and this relative instability of the uncemented femoral components could compromise the bone ingrowth. Studies on femurs retrieved at autopsy from patients who underwent cemented total hip arthroplasty two week sup to seventeen years earlier and were functioning well, have shown that the failure of cemented femoral components is initiated primarily by mechanical factors, consisting of debonding at the cement-prosthesis interface and fractures of the cement rather than lack of bone ingrowth or fibrous tissue formation at the interface. Thus the problems with using cemented femoral components involve the poor strength of the cement-prosthesis interface and the cement, while the problems with cementless components involve the difficulties in precisely machining the femoral canal, and providing rigid stability as well as accurate fit. PMID- 1297570 TI - Considerations on ceramic prosthesis explants. AB - The authors report data obtained for 11 cases of explants of prostheses having ceramic joint surfaces. The wear phenomena observed in 9 prostheses, including 1 case with breakage of the ceramic head, was moderate: 20-22,000 debris per mu 2. In 2 cases the wear was massive, with a concentration of debris in the peri implant tissues 5-10 times greater (100,000-218,000 debris per mu 2). An explanation for the trigger mechanism of wear phenomena is proposed: the cases of massive wear are related to loosening of the acetabulum. A histological examination of the bone tissue surrounding a stem covered with alumina (Al2O3) carried out in three cases allowed us to observe an area of demineralization measuring approximately 500 mu of tissue in contact with the ceramic coating. The osteomalacia could be caused by the diffusion of alumina ions. PMID- 1297571 TI - Clinical experience with primary cemented total hip arthroplasty. AB - Results obtained with 433 cemented prostheses with original design, implanted at Exeter since 1969, are presented. Clinical and radiographic findings were evaluated on 88% of cases at 7,4-13, 4-16, 4 follow-ups. Average age at surgery was 66,7 years. Sixty-two (14,3%) prostheses have been revised. Stem loosening was evident in 13 (3%) cases, of which 11 were revised. Socket loosening was evident in 21 patients (4,9%), all revised. Due to sepsis 7 prosthetic were explanted (Girdlestone) were done. Stem sinking > 2 mm into the cement mantle was observed at 16,4 years follow-up in 15% of cases, with no relation to pain. None of the patients showed a complete radiolucent line around the stem. The biomechanical relevance of the tapered design of a smooth and collarless stem for the cemented implant is discussed. PMID- 1297572 TI - Clinical experience with primary cementless total hip arthroplasty. AB - One hundred-eleven patients (121 hips) treated with cementless total hip arthroplasty (Harris-Galante, Zimmer) were clinically and radiographically reviewed at an average follow-up of 67 months (55-79). 9,1% of the stems presented signs of loosening and 5 stems (4,1%) had to be revised. None of the acetabula required revision surgery for loosening. One socket was revised due to recurrent dislocation. Clinical results were evaluated according to Harris protocol: excellent 75,2%, good 12,4%, fair 5%, poor 3,3%. Ten (7,9%) intraoperative fractures of the proximal femur were observed: in 2 cases stem instability consequently occurred. Endosteal cortical erosions, not clinically evident, were observed in 8,3% of stable stems. A foreign body biological reaction to polyethylene or metallic debris is supposed as cause of erosions. PMID- 1297573 TI - Borderline indications for use of cement in total joint replacements. AB - In order to delineate the borderline indications for the cemented and uncemented total hip replacements, we need to evaluate the existing success rates with these procedures. The long term success rates with cemented total hip replacements done using an intramedullary methylmethacrylate plug, doughy Simplex bone cement introduced in a retrograde fashion via a cement gun, and collared cobalt-chrome femoral components with rounded corners were reviewed at eleven year follow-up. The patients ranged in ages from 20 to 84 years (mean 57 years). Among the 105 patients in the group followed up at a minimum of 10 years 97% of the femoral components remained rigidly fixed. These results suggest that the cemented femoral components give satisfactory results to the vast majority of patients over eleven years. Further improvements in the use of cement for prosthetic fixation were made since then. The strength of the cement-prosthesis interface is now considerably enhanced by precoating the prosthesis industrially with a thin layer of methacrylate and or by using texture prosthesis. The strength of cement is considerably improved by techniques such as centrifuging the cement after mixing, or mixing the cement in vacuum. These techniques appear promising and may further enhance the fixation of the prostheses to the skeleton. PMID- 1297574 TI - Radiographic evaluation of HDPE cemented and cementless Lord and An.C.A. screwed acetabular models. AB - A total of 187 alumina screwed porous-ceramic coated sockets (An.C.A.), 48 screwed smooth-surfaced Lord sockets, and 251 cemented polyethylene sockets were radiographically evaluated at an average follow-up of 30, 51 and 96 months respectively. After 6 years the Lord prostheses revealed a 38% incidence of loosening, similar to that observed for cemented sockets 10-12 years after surgery. The An.C.A. prostheses revealed radiographic loosening equal to 12% (6 cases) in the first 50 implants, and only 0.7% in the remaining 137 cases: overall, the An.C.A. acetabular prosthesis revealed an index of radiographic loosening equal to 3.3% (7/187). To guarantee "osteointegration" of the porous coating of An.C.A. sockets optimal stability must be obtained when the prosthesis is screwed in. Because the mid-term follow-up for this clinical experience is relatively short (30 months), an opinion on the reliability of the screwed "porous" sockets must await confirmation. PMID- 1297575 TI - Bone remodeling in experimental total hip arthroplasty. AB - Experimental studies of cementless porous-coated total hip arthroplasty indicate that the most important design variable for femoral remodeling is stem stiffness. In the long-term (2 years) in the canine model, other variables including the presence, type and placement of the porous coating did not significantly affect the pattern of bone remodeling when tested with metallic stems. The basic pattern of bone remodeling was characterized by proximal cortical atrophy, and distal cortical and medullary bone hypertrophy. The use of low stiffness stems altered this pattern, leading to reduced proximal bone loss and no distal cortical hypertrophy. PMID- 1297576 TI - Femoral bone remodeling: clinical experience with cemented and cementless total hip arthroplasty. AB - A radiographic study of femoral bone tissue remodeling around hip arthroplasty was carried out simultaneously in two series totalling 224 cementless and 77 cemented prostheses. Remodeling was analyzed by detailed visual evaluation of the radiographic assessment. The results show that the phenomenon of bone remodeling is still evolving more than 5 years after surgery. Bone demineralization of the proximal femur is more evident in cementless prostheses than in those stabilized with acrylic cement (24% vs. 12%). The preoperative state of mineralization significantly influences bone remodeling. PMID- 1297577 TI - Charnley total hip prostheses: clinical and radiographic results after 10 to 18 years. AB - The work reviews 76 Charnley cemented total hip prostheses applied between 1970 and 1977 using a traditional cementation technique. Long-term results after an average of 12 years (minimum 10 and maximum 18) were excellent or good in 79% of the cases, fair in 2.6% and poor in 7.9%. The revision rate was 10.5% Cases characterized by radiographic signs of loosening were studied in detail, and correlations with clinical and radiographic data searched for. PMID- 1297578 TI - Indications and limits of hybrid hip prostheses (cementless acetabulum and cemented stem). AB - The authors report the indications and short-term results obtained in a series of 99 total hip prostheses with a screwed acetabulum and cemented stem. The principles which inspired their choice and the criteria used to select patients are discussed. The results obtained, evaluated both clinically and radiographically, are satisfactory, particularly with regards to percentage of pain symptoms in the femur. PMID- 1297579 TI - Cemented hip prostheses: modular screw system. AB - The long-term results of 21 patients treated with modular screw cementless hip prostheses are reported. An examination of periprosthetic osteogenesis and function evaluated by gait analysis revealed good incorporation of the prosthesis and good clinical results in all of the cases studied. PMID- 1297580 TI - Identifit: a silicone mould used to intraoperatively construct a cementless femoral stem. AB - A new system named Identifit to construct a femoral stem for use in hip arthroplasty is presented: a silicone mould of the femoral canal is made, and while the surgeon proceeds to insert the acetabulum, in a laboratory located annexed to the surgical theater the mould is used to make a titanium stem in the same shape. The stem is anatomical with a mean value for bone to prosthesis contact equal to 94%. The first results obtained seem to confirm the theoretical effectiveness of this system. PMID- 1297581 TI - Rehabilitation treatment in cemented and cementless prostheses. AB - Rehabilitation after hip arthroplasty is aimed at improving the results obtained with surgery and allowing the elderly patient to resume a normal daily life as quickly as possible. The correct use of the prosthesis positively influences its duration. Full weight-bearing on the limb submitted to surgery is allowed at different times: days 7-8 if the prosthesis is cemented. When the prosthesis is cementless the proper time for full weight-bearing is established by the orthopaedist, and it is usually allowed on days 30-40. Walking initially makes use of a walker, followed by parallel, and finally antibrachial support. PMID- 1297582 TI - [Rhythms and blues]. PMID- 1297583 TI - [Sleep disorders in psychiatric diseases. Epidemiological aspects]. AB - Very few epidemiological surveys have specifically studied relationships between sleep disturbances and psychiatric diseases. In this review, we preferred to use the classification proposed in 1979 by the Association of Sleep Disorders Centers. It includes four main categories: insomnias, excessive sleepiness, troubles of the wake/sleep schedule and parasomnias. Evaluating psychiatric disorders among general populations is easier owing to DSM III and DSM III-R criteria, but there are not equivalent criteria in evaluating sleep disorders. It is almost impossible to realize polysomnographic recordings in large samples, therefore sleep disorders are to be detected by questionnaires. It has been shown that there is a good correlation between self-reports and polysomnographic recordings among clinical and general samples. The prevalence of insomnia, defined as difficulties of initiating and maintaining sleep, is estimated between 9 and 31%. It is higher among women, elderly people, separated and divorced subjects, and low educational levels' groups. It has to be noticed that polysomnographic records of some subjective insomniacs are not different from those of good sleepers, sleep latency excepted. These subjective (and not objective) insomniacs have high scores in anxiety scale, depression scale, or psychologic distress. Insomnia is more frequently noted amongst subjects with psychiatric diagnoses, especially major depressive disorders and anxiety disorders. Depressive disorders are present in 21-40% of insomniacs versus 0-1% of non-insomniacs, and anxiety disorders in 13-24% of insomniacs versus 3-10% of non-insomniacs. In depressive disorders, sleep alterations are frequently noted: they are difficulties of initiating and maintaining sleep, decreasing proportion of slow-wave sleep, decreasing time of REM (rapid eye movement) sleep and REM sleep latency, and increasing density of REM sleep. Of these modifications, the last two ones seem to be specific for depression. The relationships between sleep, aging and depression are more complex than previously noted. For example, differences between depressed and non-depressed subjects depend on the age of the population. The prevalence of hypersomnia is lower than the insomnia's. It varies between 2 and 4%. It is more frequently noted among young people, and never married subjects. Two specific aetiologies must be looked for: sleep apnea syndrome and narcolepsy. These diagnoses are respectively found in 45% and 24% of hypersomniacs examined in American Sleep Centers. Hypersomnias are objectived by the Multiple Sleep Latency Test, which measures the physiologic sleep tendency.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297584 TI - [Sleep disorders in psychiatric diseases. Clinical and polygraphic data]. AB - This article considers first the relationships between sleep disturbances and psychiatry in general. It shows the interest of sleep recordings in psychiatric diseases as a complementary examination, in order to clarify a diagnosis or the selection of a treatment. Sleep disturbances in the main psychiatric disorders are described: brain organic diseases, thymic disorders, schizophrenia. Modifications of sleep are also found in many other psychiatric disturbances such as anxiety or neuroses. Polysomnography is an excellent functional examination of the brain and has an increasing importance in psychiatry. PMID- 1297585 TI - [Parasomnia]. AB - The parasomnias comprises a group of disorders that intrude into the sleep process and are not primarily disorders of sleep and wake states per se. These disorders are manifestations of central nervous system activation usually transmitted through skeletal muscle or autonomic nervous system channels (ICSD 1990). The parasomnias are divided into four groups: Arousal disorders (sleepwalking, night terrors, and confusionnal arousal), sleep-wake transition disorders (rhythmic movement disorder, sleep starts), REM sleep parasomnias (nightmares, sleep paralysis, hallucinations, and REM sleep behavior disorders), and other parasomnias (sleeptalking, nocturnal enuresis, and nocturnal bruxism. PMID- 1297586 TI - [Sleep apnea syndrome: psychiatric aspects]. AB - The prognosis of sleep apnea syndrome (SAS) is dominated by cardiovascular complications. However, this disease is concerned with psychiatric field through specific clinical patterns. Nocturnal respiratory arrests are responsible for hypoxic and hypercapnic events including sleep fragmentation, reduction of slow wave sleep and rapid eye movement sleep. Alertness disturbances and sleep disorders are the most common functional complaints. Memory and cognitive disorders, personality changes and anxiodepressive syndromes may occur but are often neglected due to the increase of frequency with age together with the frequency of SAS; clinicians should consequently be aware of the fact that such troubles may be related to sleep respiratory disorders. In this case polysomnography should be performed before prescribing hypnotics, tranquilizers or sedative antidepressants. PMID- 1297587 TI - [Consumption of benzodiazepines in a university hospital center]. AB - Benzodiazepine consumption has been studied in an inpatient population of a hospitalo-universitary center. The different user wards were classified by their cost or the importance of their benzodiazepine use. In a second step, the authors studied the prescription in the 6 most consumer medical wards. The most prescribed benzodiazepines were lorazepam and dipotassium clorazepate (27 and 23% respectively). In these six wards, on the day of the study, 48% of the 227 inpatients were taking benzodiazepines. Fourteen out of them were taking more than one of these drugs. In 80% of the cases, the patient was asking for the prescription. Out of the 110 inpatients found to have taken a benzodiazepine on the day of the study, 74 had already regularly used it during the years before hospital admission, mainly women (64%) and old people. Finally, out of the 227 inpatients studied, the hospitalization is a possible inducer of the benzodiazepine intake and dependence in 16% of the patients. The results are discussed against the background of other studies concerning benzodiazepine consumption. PMID- 1297589 TI - [Equity and efficacy: what about cooperating with managers?]. PMID- 1297588 TI - [Bulimia and epidemiology]. AB - Despite the multiplication of the epidemiological studies related to bulimia, the prevalence of the syndrome remains difficult to estimate, due to the variance of the results. 1 to 17% of the students will be bulimic. Numerous methodological imperfections may explain this disparity. In the studies the populations differentiate in accordance with age, social or economical level or ethnic group. Furthermore many of them were not randomly selected. Additionally, a few studies draw a comparison between the respondents and the sample from which they were drawn. This comparison is very important when the response rates are low. These two factors weaken the representation of the studies. All but one of the studies evaluated subjects by means of self-report questionnaires. The terms used are often not precise enough and there is a risk that individual subjects will interpret them idiosyncratically. Moreover, a lot of these questionnaires were pioneered in the studies, and reliability and validity data are lacking. The screening instruments "BITE" and "BULIT" have been formally evaluated, although they have not been used for the epidemiological evaluations. The BEQ has a good reliability, but has a low rate of identifying false positives. Studies using these self-report questionnaires operationalize the DSM III, the DSM III-R or the Russell criterias. As far as bulimia is concerned, there exist a small relationship between DSM III and DSM III-R. Furthermore, the DSM III criteria for bulimia have been criticized for being overinclusive. The inclusion in the DSM III-R of "methods of weight control" and "a persistent overconcern with shape and weight" contribute to decrease the prevalence of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297590 TI - [Semmelweis the statistician]. PMID- 1297591 TI - [Cesarean section: descriptive epidemiology. Increase in frequency of indications for cesarean section]. AB - The use of caesarean section is constantly increasing in all countries of the western world. This article considers various aspects of the phenomenon, from the most frequent justifications for the increase in caesarean sections, to the consequences of this practise on the health of the mother and of the fetus/newborn infant. The often-suggested link between the increase in the number of caesarean births and the decrease of the perinatal mortality rate is also discussed. The caesarean section is potentially capable of offering large benefits, but at the same time is not without risk for the mother and the child. In order to reduce this risk meticulous attention must be paid to the anesthesiological and surgical techniques employed and surgery must be used only when absolutely necessary. PMID- 1297592 TI - [The impact of AIDS on mortality in Italy]. AB - Using the official mortality data, collected by ISTAT, and the data of the Italian Register of AIDS cases, in Istituto Superiore di Sanita, three arguments have been developed: 1) Study of causes according to which ISTAT could classify deaths from AIDS: the leading cause appears to be "Deficit of Cell Immunity" (I.C.D. 279.1). 2) Study of the under-estimation of official data with respect to those of the specific system. Under-estimation decreased over the years, reaching 20% in 1987 and 6% in 1988. 3) Analysis of the general mortality trend in all of Italy and in particular metropolitan areas, with a high concentration of cases, such as Rome and Milan; there is evidence of a possible influence of AIDS deaths on mortality of young age classes particularly notable among single males. PMID- 1297593 TI - [Psychiatric hospitalization in public wards and in private clinics. A comparative study on a population of a district of Turin from 1981 to 1988]. AB - After the 1978 psychiatric reform law, public inpatient facilities (SPDC) and private clinics, with a higher number of available beds, coexist in the metropolitan area of Turin. Presented data, concerning the population of a specific catchment area, allow a comparison between the admissions in the two kinds of facilities. Patients hospitalized in 1981 were followed up to 1989, evaluating their contacts with the Community Mental Health Centre (SSM). A higher number of admissions in private clinics emerges, but there is no progressive increase during the considered period. The SPDC has evolved towards a sort of 'specialization' in psychotic syndromes; lengths of stay, moreover, were shorter. Public services (SPDC and SSM) seem to play a limited role in meeting the demand for psychiatric care expressed by the considered population. PMID- 1297594 TI - [Economic efficiency and effectiveness in health care: the economist's perspective]. AB - The debate on the efficiency of the health care system in Italy requires a developing dialogue between clinicians, epidemiologists and health economists. In this perspective the meaning of economic efficiency and its relationship with effectiveness are presented, either at production unit level either at system level. Application of criteria of efficiency is not independent from value judgements. The conflict between clinical freedom and controls on health care expenditure have ever been and it may not be eliminated, but compounded by expliciting the criteria of choice and by defining the responsibilities of health policy makers and clinicians. An example is represented by the recent Oregon's experiment. In the agenda of the future change of the Italian National Health Service, mechanisms of cost-effectiveness resource allocation criteria are suggested to be included. PMID- 1297595 TI - Estimated confounding from smoking in a cohort of 20,000 French electrical workers. PMID- 1297596 TI - [Indications for x-rays of the skull and cervical spine: an open question]. AB - During the first six months of 1990, a study was carried out on a group of patients examined at the Neuroradiology Department of a Neurological Institute for skull and cervical spine X-rays. Kind of disturbances, the examination prescribed and patients' places of origin were taken into consideration. We studied 174 patients: 108 suffering from headache, 28 from cervical arthrosis, and the others from miscellaneous diseases. Male/Female ratio (M/F) was lower in the group affected by headache; the age was more advanced in the group affected by cervical arthrosis. Skull X-rays were usually normal in headache patients; cervical X-rays were not informative in cervical arthrosis patients. We can conclude that only through a different relationship between the prescribing physician and the Radiologist it will be possible to approach the justification and optimization criteria of medical radiological exposure. PMID- 1297597 TI - [Mortality of psychiatric patients. A retrospective cohort study of in-patients at the Psychiatric Hospital of Reggio Emilia]. AB - The authors report the results of historical cohort study in long-term patients of psychiatric hospitals in Reggio Emilia. The cohort was formed by 790 patients hospitalized before 1978, and has been followed-up until 31/12/'89. The results of the study are: 269 subjects deceased (34%); 117 discharges (14.8%) and 411 (52.1%) still in hospital on 1/1/'90. An excess mortality was observed in the cohort. Mortality appears to be particularly high among young patient and females. PMID- 1297598 TI - [Lung cancer and occupation: attributable risk in the province of Trieste]. PMID- 1297599 TI - [Environmental and occupational exposure risks: information to the public]. PMID- 1297601 TI - [Action profile of a semisynthetic human isophane zinc insulin compared with customary isophane insulin]. AB - Addition of zinc to a protamine-isophane insulin should probably allow to lengthen its duration of action. Therefore we compared the action of this new type of insulin (NPH Zn) with that of a classical protamine-isophane NPH insulin (NPH); both were manufactured by the same firm. Five healthy volunteers were connected to an artificial pancreas. 0.6 U/Kg of insulin was injected subcutaneously in the low left quarter of the abdominal wall. Insulin action was monitored by the glucose needs delivered by the artificial pancreas working in euglycemic glucose clamp mode. Each insulin were tested in every subject at a ten day interval. The peak plasma insulin levels were observed after 2 h 30 for the NPH insulin (40 +/- 17 microU/ml) and after 3 h (47 +/- 22 microU/ml) for the NPH Zn insulin. The glucose needs reached their top levels after 2 hours (102 +/- 19 mg.kg-1 x 15 min-1) for NPH insulin and after 3 hours (98 +/- 28 mg.kg-1 x 15 min 1) for NPH Zn; the glucose needs decreased on a parallel way for both insulins but a one hour delay for NPH Zn insulin was observed. Addition of zinc to isophane NPH insulin slightly modifies the pharmacokinecinetic parameters, moving forward one hour in the glucose delivery. PMID- 1297600 TI - Stabilization of severe proliferative diabetic retinopathy by long-term treatment with SMS 201-995. AB - Growth hormone and growth factors have been implicated in the pathogenesis of diabetic retinopathy. Hypophysectomy has been proposed as a treatment for proliferative diabetic retinopathy unresolved by panretinal photocoagulation (PPC). SMS 201-995, a long acting somatostatin analogue which slows down growth hormone secretion, may provide a non-invasive therapy for these rare cases. To assess this possibility, we studied the feasibility and efficiency of long-term SMS 201-995 treatment in diabetics. SMS 201-995 was injected subcutaneously with a continuous pump system at a dose of 400 micrograms/d into 4 insulin dependent diabetic patients suffering from proliferative diabetic retinopathy progressing despite a pan-photocoagulation. The mean age of these patients was 29 +/- 3 years and mean disease duration 18 +/- 3 years. Treatment periods lasted from 6 to 20 months (mean 15 months). Mean 24-hour growth hormone levels decreased by 57% after only one month of treatment (7.4 +/- 1.9 mU/l to 3.2 +/- 0.9 mU/l). The decline continued up to the third month. After the sixth month, signs of resistance to the drug were noted. The frequency of 24-hour GH peaks over 10 mU/l followed a parallel pattern. No rebound was observed when the treatment was progressively discontinued. In 2 patients neovascularization stopped. In the other 2 the process regressed. In all treatment had beneficial effects on the retina. Overall visual acuity improved (7.8 +/- 0.8/10e vs 5.5 +/- 0.8/10e). These effects were obtained within 3 to 6 months. Glycosylated haemoglobin levels did not change (8.8 +/- 1.3% to 9.0 +/- 0.8%). Insulin doses decreased 41% (46.5 +/- 1.7 U/d to 27.3 +/- 3.0 U/d). No severe hypoglycaemia occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297602 TI - HLA DQA1 and DQB1 study in Algerian type 1 diabetes families. AB - The distribution of HLA class II alleles associated with insulin-dependent diabetes mellitus (Type 1) in the Algerian population is poorly known. We have typed 36 Algerian Type 1 diabetic probands and their families using DQA1 and DQB1 oligonucleotide probes. Fifty-nine parental haplotypes non transmitted to diabetic offspring served as controls. The frequencies of DQA1 and DQB1 alleles and haplotypes and their associations with Type 1 diabetes were, except minor differences, similar to those reported in French. Susceptibility DQA1 (Arg52+) and DQB1 (Asp57-) alleles were significantly increased among patients versus controls (90% vs 53%, RR = 8.4, p < 10(-6), and 94% vs 64%, RR = 9.4, p < 10(-5), respectively). 85% of Type 1 diabetics versus 34% of control haplotypes were either DR3DQw2 or DR4DQw8 susceptibility haplotypes (DQA1 Arg52+, DQB1 Asp57-) (RR = 10.8, p < 10(-7). 75% of the probands vs 14% of the controls (RR = 18, p < 10(-5)) and 73% of affected siblings versus 24% of unaffected siblings (RR = 8.4, p < 0.02) possessed a genotype composed of these two susceptibility haplotypes in the homozygous or heterozygous state. 42% of the probands were DR3DQw2/DR4DQw8, corresponding to Hardy-Weinberg expectations. The lack of excess of heterozygotes could be due to the consanguine families in this sample, as among the patients with consanguine parents the frequency of DR3, 4 heterozygotes was lower (27% vs 48% in non-consanguine patients, NS) and that of DR3 homozygotes increased (45% vs 12%, respectively, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297603 TI - [Insulin autoantibodies and insulin-induced antibodies in children with insulin dependent diabetes]. AB - AIM OF THE STUDY: The aim was to study the time course of development of insulin antibodies during the first months of treatment in diabetic children, under human insulin therapy, and to see whether the presence of insulin autoantibodies influenced the subsequent binding to insulin. METHODS: Anti-insulin antibodies were measured using a radio-binding assay in 16 diabetic children, aged 4-13 years, before the first insulin injection and at regular intervals until the 9th month of treatment. RESULTS: Insulin autoantibodies were detected in 11 out of the 16 children at the time of diagnosis. Binding to insulin increased significantly after one month of treatment in these children, and after 2 months in the children with no insulin autoantibodies at diagnosis. After 2 months insulin therapy, all the children demonstrated antibodies against insulin. Insulin binding at 9 months was not correlated to the baseline values. Anti insulin antibodies develop rapidly and frequently under human insulin, and are not influenced by the presence of insulin autoantibodies. PMID- 1297604 TI - Morning peripheral insulin effectiveness and night changes in growth hormone, blood glucose and basal insulin needs in patients with type 1 diabetes mellitus. PMID- 1297606 TI - Bed time NPH-insulin plus combined sulfonylurea-biguanide oral therapy for treating refractory non insulin dependent diabetic patients. PMID- 1297605 TI - Sex differences in plasma cholesterol and apolipoprotein B levels in non-obese type 2 diabetic subjects. PMID- 1297607 TI - Effect of biguanides on insulin release from isolated pancreatic islets. PMID- 1297608 TI - [Blood glucose self-monitoring in 1993]. PMID- 1297609 TI - [GISSI and "informed consent"]. PMID- 1297610 TI - Catheter ablation of accessory pathways in patients with Wolff-Parkinson-White syndrome. AB - PATIENTS: Fifty-two patients with Wolff-Parkinson-White syndrome underwent transcatheter ablation. All patients were symptomatic. Eighteen had documented episodes of atrial fibrillation, 14 of which also had reentrant tachycardias; the remaining 34 had only episodes of reentrant tachycardias. Forty-nine patients had both anterograde and retrograde conduction through the accessory pathway; 3 had retrograde conduction alone; 2 patients had 2 accessory pathways and 1 had 3. All patients were resistant or intolerant to at least 2 antiarrhythmic drugs. METHODS: All patients were treated with radiofrequency current. Ablation was considered successful if the anterograde and retrograde conduction were completely abolished. Ablation was considered unsuccessful if ablation of only 1 pathway in patients with 2 or more accessory pathways and/or modification of the accessory pathway conduction without interruption was achieved. RESULTS: Accessory pathway ablation was successfully performed in 46 out of 52 patients (88%). Fifty out of 56 accessory pathways were effectively ablated (89%). Thirty eight required a single session of ablation and 8 additional patients were successfully ablated during a second session. The number of radiofrequency current applications ranged from 2 to 13 (mean 4.1 +/- 2.5). The mean duration of the sessions was 4.30 +/- 1.50 hours (range 2.30 to 9). The mean radiation exposure for session was 55 +/- 25 minutes (range 20 minutes to 2.30 hours). Complications were observed in 2 out of 52 patients. One patient had a transient II degree type 1 atrioventricular block; another patient with severe arterial hypertension had a mild hemorrhagic stroke with complete neurological remission. FOLLOW-UP. Forty-five out of the 46 patients in whom ablation was successful were asymptomatic for arrhythmias during a mean follow-up of 8 months (range 4 to 16), without antiarrhythmic treatment, and without reappearance of preexcitation. One patient showed reappearance of preexcitation at electrocardiogram one month after the ablation, followed by an episode of reentrant tachycardia; this patient underwent a second successful ablation session. CONCLUSIONS: Our results show that ablation techniques have high success rates with no serious complications. PMID- 1297611 TI - [Radiofrequency transcatheter ablation of anomalous left atrioventricular pathways: the role of the transseptal approach]. AB - BACKGROUND AND METHODS: In this study we used two different approaches in radiofrequency catheter ablation (RFCA) of the left free wall atrioventricular accessory pathway (AP): the retrograde transaortic (TAo) approach and the transseptal (TSA) one. Our aim was to evaluate the success rate and the duration of the two procedures. From May 1, 1991 to April 30, 1992, 33 pts (23 M, 10 F; mean age 38 +/- 16 years, range 14-66) with left free wall atrioventricular AP were selected among a 57 patient population, in which RFCA was performed for arrhythmias related to the AP. In 20/33 pts (61%) stable ventricular pre excitation was present, while in 4/33 (12%) it was intermittent; in the remaining 9/33 pts (27%) only retrograde conduction through the AP was documented. In the majority of the pts (26/33) a diagnostic electrophysiologic study was performed immediately before the ablation procedure, during the same EP test. A 7 F steerable large tip catheter was used for energy delivery. In 8/33 pts, RFCA was performed by using only the TAo approach; other 7/33 pts underwent RFCA with a TSA technique after one completely unsuccessful retrograde TAo ablation and, in the remaining 18/33 pts, the TSA approach was used electively and continuously from January 1992. Overall, the TAo procedure has been carried out in 15 cases, while the TSA one in 25 cases. In the latter group, the ablation catheter was positioned against the left atrioventricular groove through a patent foramen ovale in 5/25 cases (20%), while a TSA puncture was needed in the remaining 20 cases. After successful ablation, the observation period was prolonged up to 60 min. RESULTS: Complete AP ablation was achieved in 31/33 pts (94%), while the remaining 2 pts underwent surgical cryo-ablation after unsuccessful TAo procedure. Among the three different subsets of pts, the success rate was as follows: 40% (6/15 cases) by using TAo technique, 100% (7/7 cases) by TSA after one unsuccessful attempt with the TAo technique, and 94% (17/18 cases) after single elective TSA; in the only case where the first elective TSA procedure failed, a second attempt was successful. The duration of the whole electrophysiologic test was 4.0 +/- 1.3 hours for the TAo approach vs 3.3 +/- 0.9 hours for the TSA one (p < 0.05). The mean fluoroscopy time was significantly (p < 0.05) shorter in pts who underwent elective TSA (43 +/- 27 min), than in pts who underwent only TAo approach (68 +/- 42 min) or both TAo and TSA approach (157 +/- 54 min). No complication during or after the procedure was observed in any case. CONCLUSIONS: In RFCA of left free wall atrioventricular APs, the TSA approach seems to be as safe as the TAo approach. In this preliminary experience, the success rate and the short duration of single elective TSA procedure suggest that this can be used as a first-choice approach in these pts. PMID- 1297612 TI - [Radiofrequency transcatheter ablation in the treatment of WPW patients. Its current role between so much enthusiasm and some reservation]. PMID- 1297613 TI - [Endomyocardial biopsy in heart transplantation: the experience of the Naples Center]. AB - From January 1988 through August 1992, 38 cardiac transplants were performed. 385 endomyocardial biopsies (EMBs) from 32 cardiac allograft recipients were investigated. In 21 (5.45%) EMBs the specimens were inadequate for the diagnosis. In the remaining 364 EMBs the grades of acute rejection were: minimal in 213 (58.51%) EMBs, mild in 132 (36.26%), mild/moderate in 12 (3.3%) and moderate in 7 (1.93%). The most reliable histologic feature of acute rejection was the myocyte necrosis or damage in presence of pironinophilic mononuclear cell infiltrate, so our therapeutic protocol requires myocyte damage to perform an additional treatment, which was performed in 7 cases (1.93%). An intermediate grade mild/moderate, was introduced to classify the EMBs in which the myocyte necrosis was scant or not clear. In these patients another EMB was performed after 3 or 5 days. One patient died of chronic rejection 17 months after the transplant. Changes not related to acute rejection were: ischemic early or late necrosis; changes related to previous biopsy site; subendocardial infiltrate of mononuclear cells (Quilty's alteration); focal, diffuse or perimyocytic fibrosis and artefacts as contraction bands; nuclear or cytoplasmic vacuolar alterations. Some of these changes occasionally made the diagnosis hard or the specimens inadequate for the diagnosis. In spite of these diagnostic difficulties, the EMB is a safe and reliable invasive investigation which plays an important role in the management of rejection in cardiac allograft recipients. PMID- 1297614 TI - [The PTCA of venous grafts: the immediate and long-term results]. AB - BACKGROUND AND METHODS: From June 1981 to September 1991, 30 coronary angioplasty procedures were performed in 25 patients with lesions of saphenous vein grafts. The mean time between bypass surgery and PTCA was 63.1 months (range: 2-168 months). The clinical indications for PTCA were: stable angina in 25 cases; unstable angina in 2 and silent ischemia in 3. The treated lesions were localized at the proximal anastomosis site in 12 cases, in the midshaft in 11 and at the distal anastomosis in 10. IMMEDIATE RESULTS: Twenty-five procedures (83.3%) were successful with a mean residual stenosis of 24% +/- 9%; 1 procedure was unsuccessful and 4 were complicated (13.3%) (1 death in the catheterization laboratory; 1 non Q wave acute myocardial infarction, and 2 emergency bypass operations). The only factor predicting the immediate result was the stenosis morphology (p < 0.05). LONG-TERM CLINICAL FOLLOW-UP. The 20 patients with a first successful PTCA were followed up clinically for a mean period of 36.3 months (range: 1-120 months). There were no deaths nor acute myocardial infarctions. Ten patients (50%) remained completely asymptomatic for the follow-up period. Ten subjects (50%) had recurrence of angina, treated medically in 4 (20%) and with a repeat PTCA in 6 (30%) (for restenosis in 5 cases and for disease progression in 1). Three (15%) of these patients with a repeat PTCA had a new recurrence and were sent to surgery. Sixty-five percent of the patients where asymptomatic at the last clinical control after one or repeat PTCA. We did not find any statistically significant predictor of events (angina) at follow-up. CONCLUSIONS: In our experience PTCA for lesions of saphenous vein grafts is a feasible procedure with acceptable initial success and a favourable long-term outcome. PMID- 1297615 TI - [The adenosine test in association with 99m-technetium sestamibi tomoscintigraphy in the diagnosis of coronary pathology]. AB - BACKGROUND: The exogenous adenosine is able to provoke a coronary vasodilation, which is the same as the one provoked by the papaverine and greater than the one provoked by the dipyridamole. We report our experience in using exogenous adenosine in association with technetium-99m-sestamibi tomoscintigraphy for a diagnostic test on the coronary artery disease (CAD). METHODS: We considered 22 patients (18 male and 4 female, mean age 57 years) affected by angiographically demonstrated coronary artery disease (stenoses > or = 50%). Adenosine was infused at a dosage of 0.070 mg/kg/min for 3 minutes and, if well tolerated, the dosage was increased to 0.140 mg/kg/min; in the third minute of the major dosage the radioisotope was injected. The myocardial perfusion imaging at rest was evaluated on the following day. RESULTS: The test was completed on 21 of the 22 patients, and 20 of the latter were subjected to the maximal dosage of the adenosine infusion. Clinically irrelevant adverse effects were observed in 20 cases; only one patient developed a II degree type 1 AV block. Angina occurred in 19 patients. Coronary angiography demonstrated significant stenosis of 35 vessels: the left anterior descending (LAD) in 14 patients, the left circumflex (LCx) in 8 and the right coronary artery (RCA) in 13. In detecting CAD, the test in our study demonstrated a sensitivity of 85% in the LAD disease, of 89% in the LCx disease and of 77% in RCA disease. CONCLUSIONS: The adenosine infusion associated with technetium-99m-sestamibi tomoscintigraphy demonstrated an elevated incidence of adverse effects which are of short duration and clinically irrelevant. The method was shown to be highly sensitive in detecting the CAD. PMID- 1297616 TI - [Heart valve involvement in systemic lupus erythematosus: an echocardiographic study]. AB - The purpose of this study was to evaluate the spectrum of morphologic and functional cardiac involvement in a selected population of patients with systemic lupus erythematosus (SLE) by means of echocardiography. Thirteen patients (2 male and 11 female) affected by SLE, mean age 41.9 years (range, 21-64), underwent M Mode, two-dimensional and Doppler echocardiography. Eleven patients had renal disease and 3 of them were undergoing dialysis. One patient had findings of active disease. Six patients had systemic hypertension. None had a history suggestive of rheumatic fever or infective endocarditis. At echocardiographic study nine patients demonstrated findings of valvular involvement. These alterations were defined, according to the echocardiographic features, in two types: vegetation (verrucous Libman-Sacks endocarditis) and thickening. Vegetations were present in 6 patients, involving the mitral valve in all six and the aortic valve in three. The mitral valve vegetations were more frequent on the subannular portion of the posterior leaflet. Seven patients had valvular thickening: involvement of both mitral and aortic valve was present in five, and isolated mitral or aortic valve lesions in the remaining two patients. Combined valvular vegetation and thickening were observed in 4 patients. Eight patients had mild valvular dysfunction on Doppler examination: five isolated mitral regurgitation, two combined mitral and aortic regurgitation and one combined mitral stenosis and regurgitation. In agreement with previous reports, our study shows that valvular involvement in SLE is relatively frequent. Echocardiography can identify additional patterns of valvular lesions different from the known "verrucous Libman-Sacks endocarditis". The degree of valvular dysfunction is not important. PMID- 1297617 TI - [The closure with a double-umbrella prosthesis of recanalized ducts after surgical ligation]. AB - Four patients of 5, 27, 27 and 62 years of age, who previously underwent surgical ligation of ductus arteriosus (respectively 3, 17, 19 and 17 years before), came to our observation because of recanalization of the duct. In three cases the duct was an isolated finding, whereas in the oldest patient the duct ligation had been accompanied by implantation of a Starr prosthesis in aortic position. The diagnosis of residual shunt was based on the auscultation of a continuous murmur at the left subclavicular space and on typical signs of patent ductus evidenced by Doppler interrogation. In all cases the diagnosis was confirmed by angiography; the minimal diameter of the ducts varied between 2.5 and 4 mm. Three umbrellas of 17 mm and one of 12 mm diameter were employed for the closure of the residual shunt. The implantation of the double-umbrella device was obtained with the routine transfemoral venous approach. In the youngest patient, in order to facilitate the progression of the transseptal catheter through the duct, it was necessary to create a circuit with the guide wire from the femoral vein to the contralateral femoral artery. In all four patients the shunt was completely abolished. The oldest patient underwent replacement of a malfunctioning aortic prosthesis three days after implantation of the double-umbrella device; the surgical approach was this way significantly simplified. The implantation of a Rashkind double-umbrella device is the method of choice for closure of residual shunts through the duct after surgical ligation. PMID- 1297618 TI - [Paroxysmal atrial arrhythmias in arrhythmogenic cardiomyopathy of the right ventricle with a familial character: the role of right atrial involvement]. AB - Arrhythmogenic right ventricular cardiomyopathy presents a rather frequent familial occurrence. In the present study the cases of two brothers (25 and 30 years old, respectively) presenting with the peculiar finding of early involvement of right atrium, are described. Both subjects were investigated because of recurrent complex arrhythmias, including supraventricular (sustained atrial flutter, atrial tachycardia) and ventricular tachyarrhythmias (very frequent premature beats, nonsustained ventricular tachycardia). The associated echo-angiographic aspects of the right atrium and right ventricle were those typically described in arrhythmogenic right ventricular cardiomyopathy. The familial occurrence of simultaneous right atrial and ventricular involvement, to the best of our knowledge not previously described, can likely be due to the similar phenotypic expression of the same genotype. The prognostic significance of atrial involvement in right ventricular arrhythmogenic dysplasia is still to be defined and the clinical follow-up of these two cases may contribute to it. PMID- 1297619 TI - [Acute pulmonary edema and a state of shock in a female patient with a penbutolol treated pheochromocytoma]. AB - A woman with "mild arterial hypertension" had a cardiogenic shock a few minutes after taking the first tablet of penbutolol. Subsequently, a suprarenal pheochromocytoma was discovered (and surgically excised, with stable recovery). PMID- 1297620 TI - [A posttraumatic pseudoaneurysm of the radial artery. Its diagnostic assessment by duplex color Doppler]. AB - A twenty-nine-year-old woman, one week after a traumatic skin laceration on the territory of the distal part of the radial artery, developed a pulsating mass suggesting a pseudoaneurysm of the radial artery. Using the duplex color Doppler echography, we clearly demonstrated the anatomical damage, the presence of the false lumen and the continuity of the vessel. These observations were of great assistance for the subsequent surgical treatment. PMID- 1297621 TI - [Paradoxical embolism: a case]. AB - We report a case of pulmonary embolism complicated by paradoxical embolism (which is rarely diagnosed in life). Foramen ovale patency is a relatively common condition and this, together with the presence of pulmonary embolism, increases the probability of paradoxical embolism. PMID- 1297622 TI - [The clinical significance and therapy of supraventricular tachyarrhythmias that complicate the acute and subacute phases of a myocardial infarct]. PMID- 1297623 TI - [Nuclear methods in cardiology]. PMID- 1297624 TI - Altitude, exercise, and mountain medicine: lessons from the field. PMID- 1297625 TI - Electrophysiological study on jaw-opening reflex recorded from digastric muscle in Parkinson's disease and primary cranial dystonias. AB - We investigated digastric reflex excitability in normals and in patients with extrapyramidal disorders such as primary cranial dystonias and Parkinson's disease. Relationships between exteroceptive suppression of masseter muscle and digastric reflex were also investigated in some cases. Digastric reflex hyperexcitability was observed in dystonic patients when compared to normals and parkinsonian patients. Furthermore, some patients with cranial dystonia presented absence of exteroceptive suppression reflex in masseter muscle with enlarged digastric response. These results indicate hyperexcitability of the digastric reflex and abnormal agonist-antagonist muscle co-contraction in chewing reflexes of patients with cranial dystonias. This shows that digastric reflex is an important electrophysiological investigation to explore the physiopathological mechanisms of primary cranial dystonias. PMID- 1297626 TI - Hemicrania continua: a possible symptomatic case, due to mesenchymal tumor. AB - The case of a 28-year old woman with headache resembling hemicrania continua (HC) is described. Since her childhood she had a history of right-sided, side-locked, painful headache attacks, with increasing attack frequency during the last two years, each attack lasting around 24 hours. There were only a few "migrainous" symptoms and signs, thus no photo- and phono-phobia and no vomiting. Only occasionally did she have slight nausea. The clinical picture as well as the complete indomethacin effect suggested a case of HC. However, the indomethacin effect faded away after > 2 months. At that time, a CT scan revealed a tumor in the right sphenoidal bone involving the clinoid process and the base of the skull. A biopsy of the tumor during craniectomy showed a mesenchymal tumor, and the patient was considered inoperable (April, 1989). After cytostatic treatment, she is back in full time work; the headache disappeared and it still has not recurred after approximately 2 years of observation. Neuroradiological investigation should, therefore, be included in the work-up of patients with HC. At the present stage of knowledge, neuroradiological investigations should probably also be included when faced with a typical clinical picture. PMID- 1297627 TI - Birth seasons of Cercopithecus, Cercocebus and Colobus in Zaire. PMID- 1297628 TI - Primate penile morphologies and social systems: further evidence for an association. PMID- 1297629 TI - Feeding ecology of Saguinus bicolor bicolor (Callitrichidae: Primates) in a relict forest in Manaus, Brazilian Amazonia. AB - This study is part of a long-term ecological study of habitat and dietary requirements of the pied bare-face tamarin (Saguinus bicolor bicolor). One group was studied for 11 months in an area of secondary forest in a suburb of Manaus, Amazonas, Brazil. Three main vegetation types occurred inside the group's home range (12 ha): capoeira, older secondary forest and campinarana (white sand forest). The tamarins ate fruits (21 species), flowers (1 species), exudates (4 species), and arthropods (insects and spiders). They spent 14.3% of total activity time seeking and eating animal prey, and 9.9% feeding on plant material, mostly fruits. In general, fruits consumed were ripe, small and succulent. Trees used for feeding were low and had small crown diameters. Three plant species (Protium aracouchinni, Myrcia cf. fallax, and Couma utilis) were used intensively during the three seasons covered by the study period. The concentrated use of 3 fruit species, each for an extended period (one fruiting species per season), provided the tamarins with a regular food supply. Tamarins consumed exudates from holes in the bark of trees of the families Anacardiaceae and Vochysiaceae, as well as gum exuded from seed pods of Mimosaceae. Exudates were exploited during the dry season and at the beginning of the wet season. Group travel was primarily based on routes connecting the fruiting trees exploited, with foraging for animal prey occurring during travel. Tamarins searched for arthropods on trunks, branches and leaves and in trunk holes. The foraging and feeding tactics displayed by S. b. bicolor are closely linked to morphological characteristics (small size and weight, claw-like nails) that allowed access to energy-rich resources (arthropods and plant exudates) in different strata of the vegetation. PMID- 1297630 TI - Influences of female partner preference on potential reproductive outcome in Japanese macaques. AB - The immediate effects of female partner preference on male mating behaviors and its potential influence on male reproductive success and conception in the Japanese macaque (Macaca fuscata) were analyzed. Although male dominance interactions probably led to low-ranking males having more single-day consortships and high-ranking males more multi-day consortships, dominant males were unable to prevent females from mating with preferred subordinate males. Ultimately, there was no marked difference in the number of estimated offspring sired. Females chose not to mate with certain males and actively mated with others, suggesting that female partner preferences do affect conception. Evidence for this was found in paternity estimates, which reflected observed preferences for particular middle-ranking young adult males. PMID- 1297631 TI - Capturing wild long-tailed macaques (Macaca fascicularis). AB - Long-tailed macaques (Macaca fascicularis Raffles, 1821) were captured at various locations in the north of Sumatra as part of a study on social behaviour and genetic relationships. We used individual cage traps, a group trap, a blowpipe and an air-pressure rifle. Provided that the monkeys were willing to take bait, individual cage traps proved most successful; they gave a high capture rate with minimal disturbance of the group. Success with young juveniles and peripheral animals could be improved by placing elevated traps in the centre and in clusters at the periphery of the trapping site. Trapping had no clear lasting effect on the natural behaviour of the animals. PMID- 1297632 TI - Amazing grace: religion and identity among elderly black individuals. AB - A sample of forty-three "life stories" collected from elderly African-Americans residing in Southwestern Virginia is analyzed from the perspective of Continuity Theory. The focus is on the "theme" which religion plays as a bulwark of continuity in the lives of the respondents. The data reveal that religion serves at least seven significant and positive functions in the normal aging process of Black-Americans. As is customary, all names of respondents have been changed to protect their anonymity. PMID- 1297633 TI - Older motorist yielding to pedestrians: are older drivers inattentive and unwilling to stop? AB - A field experiment investigated factors expected to influence yielding by motorists to a pedestrian waiting to cross a city street. One-hundred and sixty motorists passing through a marked crosswalk were participants. In addition, data were gathered on 120 baseline motorists who passed through the test intersection when a pedestrian was not present. A comparison of the age composition of the experimental sample with the baseline sample showed that the youngest group of drivers, i.e., under twenty-six years, was significantly more represented in the experimental sample and was more likely to stop for the experimental pedestrian than were motorists in other age groups. Contrary to a prediction that older motorists over age sixty-five would be less attentive to a pedestrian and, therefore, less likely to stop, this oldest group of drivers was not underrepresented in the experimental sample; i.e., their likelihood of yielding matched their likelihood of driving through the intersection. Further analysis, however, revealed that motorists over sixty-five years of age were significantly more likely than younger motorists to stop for a pedestrian who was conspicuously dressed (bright, highly visible clothing) and who was moving to cross the street rather than patiently waiting. Implications of these findings are discussed in terms of difficulties that older drivers have in judging the speed of moving objects in a traffic environment. PMID- 1297634 TI - The accuracy of older and younger Australians' understanding of mental health and aging. AB - Inadequacies in contemporary mental health care for elderly individuals may come about partly through ignorance of both positive aspects of mental health in old age (e.g., the responsiveness of older clients to psychotherapy) and the negative aspects (e.g., elderly men's unusually high suicide risk). A quiz measuring knowledge of both kinds was administered to a total of 250 Australian men and women aged seventeen to eighty-one years who were either retired, employed, housewives, or university students. As hypothesized, the retired group scored lowest on the quiz, with no significant differences among younger students versus non-students. Age was found to be a more important mediator of the retired group's low scores than gender, living with an older person, or self-definition as retired versus employed or a housewife. A previous finding of higher scores by Australians than by U.S. undergraduates in an aging course was also replicated and extended to older nonstudent groups. Implications of these findings for mental health services for elderly individuals and for educational interventions to improve understanding of mental health in older age groups were considered. PMID- 1297635 TI - Associations among healthy habits, age, gender, and education in a sample of retirees. AB - In this exploratory and descriptive study, data are drawn from a sample of 1,864 Bank of America retirees collected in 1987 to investigate correlations among healthy habits, age, gender, and education. Findings include: 1) Health habits are strongly and positively associated with each other and negatively associated with unhealthy habits. 2) Age is statistically significant and positively associated with fiber, fat consumption, and lack of exercise, but negatively associated with cigarette use. 3) Women are more likely than men to smoke, use seat belts, and eat foods high in fiber. Men are more likely than women to exercise and drink excessively. 4) Education is statistically significant and positively associated only with fiber in the diet and no other habit. 5) Fiber consumption emerges as the healthy habit most consistently associated with all other habits. PMID- 1297636 TI - Personality and politics among older Americans: a rural case study. AB - This study examines personality factors as predictors of political attitudes and behavior among a sample of rural older Americans. Results indicate that trait variables (extraversion, openness, and neuroticism) and measures of self-concept (locus of control) affect political attitudes and behavior in predictable ways. Suggestions for future research are outlined. PMID- 1297637 TI - A return to infancy: old age and the second childhood in history. AB - Throughout Western history scholars and writers have characterized old age as a period of a second childhood and childish behavior. The second childhood stereotype has endured and finds expression in numerous works of literature, in a variety of historical contexts including ancient through contemporary times. Explanations for this stereotype were linked to the humoral theory of aging, the perceived and actual dependency of older people for care, dementia, and other ties between childhood and old age. The second childhood was also interpreted as a stage of life where the lifecycle returned to its beginning. The stereotype, while predominantly viewed as negative, may also be viewed in a positive light and underscores the duality and ambiguity that characterized the way older people have been viewed in Western history. The stereotype, while enduring, may have been more prevalent during certain periods, such as those periods when older people were devalued. Cultural representations and more importantly interpretations have also varied within historical context. PMID- 1297639 TI - Clinical pharmacokinetics of teicoplanin and aminophylline during cotreatment with both medicaments. AB - The influence of teicoplanin and aminophylline (theophylline ethylenediamine) on their mutual steady-state pharmacokinetics was studied in two parts, namely experimental and clinical studies. The concentrations of teicoplanin and aminophylline (theophylline) were evaluated at several times after intravenous administration of teicoplanin (3 and 15 mg/kg) and aminophylline (5 mg/kg) in 12 rabbits. Ten COPD patients were treated for 5 consecutive days with a short-term intravenous infusion of 240 mg aminophylline twice daily; ten more patients received for 5 days a short-term intravenous infusion of 200 mg teicoplanin twice daily. On the last day, blood samples were taken for teicoplanin and theophylline determination by means of the HPLC method. Subsequently, while aminophylline and teicoplanin were continued at the same dosage, the first ten patients received in addition a short-term intravenous infusion of 200 mg teicoplanin twice daily, and the second ten patients a short-term intravenous infusion of 240 mg aminophylline twice daily. After 5 days the serial assays of serum teicoplanin and theophylline were repeated. Our results demonstrated, in both experimental and clinical studies, no influence of theophylline on the steady-state pharmacokinetics of teicoplanin. Likewise teicoplanin had no significant effect on the steady-state pharmacokinetics of intravenous administration of theophylline in the form of aminophylline. PMID- 1297638 TI - A new theory about the ages of man. AB - Genetic psychologists who have long been studying the periods of growth in the ages of Man, endeavoring to determine their average durations, set the limits separating these periods empirically, and do not pursue their study beyond childhood and adolescence. In my book published in Paris (1986) I propound a new, radically different approach which takes into account Man's whole lifespan, without separating the various ages, and without separating old age from those that precede it. According to my theory, the Ages of Man, nine in number, all follow the same mathematical law, which determines their respective durations on the basis of a geometrical progression, ratio two. Their durations would be of three and six months for gestation, one, two, four, and eight years for childhood and early adolescence, sixteen for youth, thirty-two for adult maturity, sixty four for old age. This amounts to a theoretical potential lifespan of 127 years. PMID- 1297640 TI - Tolerance of ofloxacin in the treatment of pulmonary tuberculosis in presence of hepatic dysfunction. AB - Twenty-nine patients with extensive pulmonary tuberculosis and drug-induced hepatitis were treated with ofloxacin along with other relatively non-hepatotoxic drugs, either during the interim phase to await recovery of liver function in some, or as definitive therapy as required by the compromised hepatic status of others. No adverse drug reactions were noted and no treatment failures were observed. This preliminary experience indicates the exceedingly good tolerance of ofloxacin when utilized in treatment of extensive pulmonary tuberculosis in the face of deranged liver function tests. Due to the small number of patients and numerous variables, no definite conclusion can be drawn on the specific efficacy of ofloxacin against Mycobacterium tuberculosis. However, it is concluded that acquisition of further clinical experience is warranted for similar patients. PMID- 1297641 TI - Bioavailability of a new controlled-release oral naproxen formulation given with and without food. AB - The influence of concomitant food intake on the plasma concentration of naproxen given as a new controlled-release (CR) formulation (750-mg tablet) was investigated in a crossover study design. Twelve healthy volunteers received a single tablet of naproxen on two occasions separated by a 3-week washout period:- after an overnight fast and immediately after a standard meal. Plasma naproxen levels were measured through HPLC at intervals suitable for obtaining concentration-time curves of both regimens in the range 1--48 hours. It was found that average plasma AUC values were 1978.7 mcg.hr/ml in fasting participants and 1778.6 mcg.hr/ml in postprandial participants. The confidence interval computed by Westlake's method indicated equivalence of values. Food decreased the peak plasma concentration of CR naproxen by about 14%, but the confidence interval (+/ 22%) barely exceeded equivalence limits. There were no significant differences between fasting versus postprandial values for the mean absorption time, or plasma absorption and disposition half-lifes. It is concluded that the bioavailability of CR naproxen is not substantially altered by the ingestion of food. PMID- 1297642 TI - T-cell alterations in immunoglobulin A nephropathy. AB - In the present paper are reported alterations of the cellular immunity found in 24 patients with immunoglobulin A nephropathy (IgAN). CD4+ and CD25+ cells were increased in patients in comparison with controls. The mean of interleukin-2 (IL 2) and interleukin-4 (IL-4) levels in sera were similar in patients and controls, but the levels of IL-2 in supernatants of stimulated peripheral blood mononuclear cells from patients were higher than those of controls. There were no correlations between renal function, serum IgA levels, urinary findings, cellular subsets, and IL-2 or IL-4 sera levels. These immunological data were also unrelated to the mode of clinical presentation. The results suggest a pivotal role of IL-2 in cellular immune response with regard to T-cell activation in patients with IgAN. PMID- 1297643 TI - Central analgesic activity of ibuprofen. A neurophysiological study in humans. AB - Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID). Inhibition of prostaglandin biosynthesis is considered to be the main mechanism of action of this substance. Recently, a central analgesic activity was described in an experimental study. In order to explore the possibility that ibuprofen induces analgesia at central level in humans, we investigated, in a double-blind design, the effects of orally-given 600 mg granular ibuprofen or placebo on nociceptive flexion reflex in normal volunteers. Ibuprofen produced a significant increase, as compared to placebo, in the threshold of the nociceptive reflex. The ratio between subjective pain threshold (Tp) and reflex threshold (Tr) was unchanged after either ibuprofen or placebo administration, indicating that Tp strictly paralleled Tr. These results indicate that ibuprofen displays a central antalgic activity in humans. Different supraspinal structures are probably involved, but the exact mechanisms are still to be clarified. PMID- 1297644 TI - Remission induction with carboplatin-epirubicin-prednimustine followed by consolidation radiotherapy in advanced ovarian cancer. AB - Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no clinical evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. This protocol was discontinued for five (23%) patients because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of ten stage-III ovarian cancer patients, who received chemoradiotherapy and were evaluable for assessment of treatment efficacy, was retrospectively compared with the survival of 11 stage-III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no evidence of disease. PMID- 1297645 TI - The TATA-binding protein is a general transcription factor for RNA polymerase III. AB - The TATA-binding protein (TBP) is a principal component of the general factor TFIID and is required for specific transcription by RNA polymerase II. We have shown that TBP is also a general factor for RNA polymerase III. PMID- 1297646 TI - Multiple effects on liver-specific gene expression in albino lethal mice caused by deficiency of an enzyme in tyrosine metabolism. AB - alf/hsdr-1 is a locus in the mouse defined by albino deletions to be essential for neonatal viability. Homozygous deletion of alf/hsdr-1 leads to a pleiotropic phenotype in liver and kidney, including impaired perinatal activation of hormone dependent genes, and the induction of detoxifying enzymes and early-response genes. To elucidate the molecular basis of this complex phenotype, we have identified the gene mapping at alf/hsdr-1 by positional cloning, using overlapping albino locus deletions to define the location of alf/hsdr-1. The gene encodes fumarylacetoacetate hydrolase, FAH, an enzyme of tyrosine metabolism. Genetically determined FAH deficiency in man leads to a severe liver failure in infants. In mice, we find that the normal sites of expression of FAH correlate tightly with cell-types which display abnormalities in albino lethal mice. The identification of the Fah gene as a candidate for alf/hsdr-1 offers a novel explanation for the complex phenotype, one into which all aspects can be accommodated. The phenotype can now be understood as a sequence of responses to toxic electrophilic metabolites. PMID- 1297647 TI - The role of the transcriptional activator protein DBP in circadian liver gene expression. AB - DBP, a liver-enriched transcriptional activator protein of the leucine zipper protein family, accumulates according to a very strong circadian rhythm (amplitude approx. 1000-fold). In rat parenchymal hepatocytes, the protein is barely detectable during the morning hours. At about 2 p.m., DBP levels begin to rise, reach maximal levels at 8 p.m. and decline sharply during the night. This rhythm is free-running: it persists with regard to both its amplitude and phase in the absence of external time cues, such as daily dark/light switches. Also, fasting of rats for several days influences neither the amplitude nor the phase of circadian DBP expression. Since the levels of DBP mRNA and nascent transcripts also oscillate with a strong amplitude, circadian DBP expression is transcriptionally controlled. While DBP mRNA fluctuates with a similar phase and amplitude in most tissues examined, DBP protein accumulates to high concentrations only in liver nuclei. Hence, at least in nonhepatic tissues, cyclic DBP transcription is unlikely to be controlled by a positive and/or negative feedback mechanism involving DBP itself. More likely, the circadian DBP expression is governed by hormones whose peripheral concentrations also oscillate during the day. Several lines of evidence suggest a pivotal role of glucocorticoid hormones in establishing the DBP cycle. Two genes whose mRNAs and protein products accumulate according to a strong circadian rhythm with a phase compatible with regulation by DBP encode enzymes with key functions in cholesterol metabolism: HMG-coA reductase is the rate-limiting enzyme in cholesterol synthesis; cholesterol 7-alpha hydroxylase performs the rate-limiting step in the conversion of cholesterol to bile acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297648 TI - Developmental regulation of globin gene expression. AB - We have used the globin family of genes in chicken to study developmental regulation of gene expression, both at the level of individual interaction of trans-acting factors with local promoters and enhancers, and at the level of chromatin structure. Regulation of all members of the alpha- and beta-globin clusters is affected by the erythroid regulatory factor GATA-1. Separate mechanisms exist for regulation of individual members of the family. As an example, we describe the control mechanisms that play a role in the expression of the rho-globin gene, which is expressed only in primitive lineage erythroid cells. In addressing the involvement of chromatin structure in gene activation, we have examined the role of locus control elements, and also considered the way in which RNA polymerase molecules might accommodate to the presence of nucleosomes on transcribed genes. PMID- 1297649 TI - cis and trans regulation of tissue-specific transcription. AB - Analysis of both the cis-regulatory sequences which control globin gene switching as well as the trans-acting factors which bind to these sequences to elicit a differential, developmentally regulated response has lent insight into the general mechanisms responsible for tissue-specific gene regulation. We show here that the chicken adult beta-globin gene promoter sequences are intimately involved in competitive interaction with the beta/epsilon-globin enhancer to regulate differentially epsilon- versus beta-globin gene transcription. Secondly, we show that the family of GATA transcription factors directs gene regulation in a variety of discrete cell types, and describe potential cellular target genes for each member of the GATA factor family, as well as potential mechanisms whereby multiple GATA factors expressed in a single cell might be used to elicit differential transcriptional activities. PMID- 1297650 TI - The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo. AB - The anterior-posterior (A-P) and dorsal-ventral (D-V) axes of the early Drosophila embryo are established by two key maternal morphogens: bicoid (bcd) and dorsal (dl), respectively. The bcd protein is expressed in a broad concentration gradient along the A-P axis, with peak levels present at the anterior pole, while dl is expressed in a gradient along the D-V axis with peak levels along the ventral surface. The two morphogens are unrelated and their gradients are formed by distinct processes. Nonetheless, we have obtained evidence that they generate sharp on/off stripes of target gene expression through a similar mechanism. Both morphogens establish overlapping patterns of transcriptional activators and repressors in the early embryo. The activators and repressors bind to closely linked sites within short (300 to 500 bp) target promoter elements that have the properties of on/off switches. The activators act in concert with the morphogen to define a broad region where target genes can be initiated. Borders of target gene expression are established by the repressors, resulting in the formation of stripes. PMID- 1297651 TI - Transcriptional control by Drosophila gap genes. AB - The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior posterior axis of the embryo: maternal transcription factors regulate the region specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva. PMID- 1297653 TI - SWI6 is a regulatory subunit of two different cell cycle START-dependent transcription factors in Saccharomyces cerevisiae. AB - Most genes involved in DNA replication in the yeast Saccharomyces cerevisiae are transcribed transiently during late G1 as cells undergo START. Their promoters all contain one or more versions of an 8-base pair motif (ACGCGTNA) called the MluI cell cycle box (MCB). MCBs have been shown to be both necessary and sufficient for the late G1-specific transcription of the TMP1 thymidylate synthase and POLI DNA polymerase genes. A different late G1-specific transcription element called the SCB (CACGAAAA) is bound by a factor containing the SWI4 and SWI6 proteins. We describe here the formation in vitro of complexes on TMP1 MCBs that contain the SWI6 protein and, we suggest, a 120 kDa protein that is distinct from SWI4. Transcription due to SCBs and MCBs occurs in the absence of SWI6 but it is no longer correctly cell cycle regulated. We suggest that SWI6 is an essential regulatory subunit of two different START-dependent transcription factors. One factor (SBF) contains SWI4 and binds to SCBs whereas the other (MBF) contains p120 and binds MCBs. PMID- 1297654 TI - Transcriptional repression by methylation of CpG. AB - Methylated DNA in mammals is associated with transcriptional repression and nuclease resistant chromatin. In this review we discuss how these effects may be mediated by proteins that bind to methylated DNA. PMID- 1297652 TI - Cyclin A recruits p33cdk2 to the cellular transcription factor DRTF1. AB - Cyclins are regulatory molecules that undergo periodic accumulation and destruction during each cell cycle. By activating p34cdc2 and related kinase subunits they control important events required for normal cell cycle progression. Cyclin A, for example, regulates at least two distinct kinase subunits, the mitotic kinase subunit p34cdc2 and related subunit p33cdk2, and is widely believed to be necessary for progression through S phase. However, cyclin A also forms a stable complex with the cellular transcription factor DRTF1 and thus may perform other functions during S phase. DRTF1, in addition, associates with the tumour suppressor retinoblastoma (Rb) gene product and the Rb-related protein p107. We now show, using biologically active fusion proteins, that cyclin A can direct the binding of the cdc2-like kinase subunit, p33cdk2, to complexed DRTF1, containing either Rb or p107, as well as activate its histone H1 kinase activity. Cyclin A cannot, however, direct p34cdc2 to the DRTF1 complex and we present evidence suggesting that the stability of the cyclin A-p33cdk2 complex is influenced by DRTF1 or an associated protein. Cyclin A, therefore, serves as an activating and targeting subunit of p33cdk2. The ability of cyclin A to activate and recruit p33cdk2 to DRTF1 may play an important role in regulating cell cycle progression and moreover defines a mechanism for coupling cell-cycle events to transcriptional initiation. PMID- 1297655 TI - Identification of Fos target genes by the use of selective induction systems. AB - c-Fos is a major component of the transcription factor AP-1 which has been implicated in the control of cell proliferation and differentiation as well as in transformation. In order to identify Fos target genes involved in these processes, we have taken advantage of the regulatory properties of the hormone binding domain of the human estrogen receptor to develop transcriptional and post translational induction systems, both of which allow selective elevation of Fos activity within a cell. Using this approach we have searched for Fos-responsive genes in rat fibroblasts and PC12 cells. Here we describe the identification and regulation of five Fos-responsive genes encoding a transcription factor (Fra-1), a secreted protein (Fit-1), a biosynthetic enzyme (ODC) and two membrane associated proteins (annexin II and V), respectively. The post-translational induction system was also used to study the Fos-mediated block of neuronal differentiation of PC12 cells. These experiments demonstrate that Fos activity is dominant over NGF function and interferes with the expression of late NGF inducible genes. PMID- 1297656 TI - [Scleral erosion after surgery of retinal detachment disclosed by isolated corticodependent hyalitis. Apropos of 3 cases]. AB - A chronic steroid-dependent hyalitis was the first sign of a transscleral erosion in three patients with severe myopia. This erosion was seen for more than 5 years after the procedure which consisted of a very tight scleral buckling with a 5 mm wide Lincoff sponge. Hyalitis disappeared in all three cases after removal of the material. In one case, the transscleral erosion was the cause of a recurrent retinal detachment. The sensitivity of hyalitis to oral steroid therapy suggests an immune process. Hyalitis in patients with a tight buckle must be cured by removal of the material. PMID- 1297657 TI - [Spontaneous reattachment of retinal detachment caused by small atrophic holes]. AB - Spontaneous retinal reattachment developed in 8 eyes with retinal detachments due to atrophic holes in lattice. The scar was characterized by massive proliferation of the pigment epithelial cells. The fundus changes were associated with an absolute scotoma of the corresponding visual field. PMID- 1297658 TI - [Results of early treatment of congenital strabismus]. AB - The authors analyse the results obtained after very early treatment of Esotropia in 38 children. These children were divided into 4 groups according to their age at the time of treatment. At the age of 30 months, they studied binocular vision, manifest latent nystagmus (NML) and dissociated vertical deviation (DVD). In groups 1 and 2, treatment was instituted before the age of 6 weeks (13 children) no DVD was noted, only one NML and 11 children have binocular vision. In groups 3 and 4, treatment was instituted after the age of 3 months (25 children) 4 cases of DVD and 10 of NML are noted, and only 9 children have binocular vision. In case of congenital esotropia, the authors recommend treatment before 2 months old to obtain a possibility of binocular vision and to decrease the risk of NML and DVD. PMID- 1297659 TI - [Serous retinal detachment. Value of acetazolamide]. AB - The effect of acetazolamide in the treatment of chronic macular edema has been well established. The pharmacologic action of this product suggested possible efficacy in the treatment of serous retinal detachment. We studied 38 patients presenting with serous retinal detachments of various etiologies divided into four groups: age related macular degeneration, central serous chorioretinopathy or diffuse epithelial retinopathy, epiretinal membranes, and other causes. Treatment with acetazolamide, at a dosage of 0.375 g/day, in three divided doses was proposed for five weeks. We observed a reduction of metamorphopsia in all cases, a stability or even an improvement of visual acuity, and a resorption of serous retinal detachment confirmed by decreased pooling of fluorescein on the angiographic examination. Considering each etiology, clinical and angiographic findings demonstrated the value of this treatment, although this study was not prospective. The encouraging results observed in many cases, raise hopes concerning the treatment for these diseases, usually not amenable to treatment. PMID- 1297660 TI - [Stilling Duane syndrome and MRI: 2 preliminary results]. AB - Dynamic mode magnetic resonance imaging (DMMRI) allows good visualization of the oculomotor muscles and allows their dimensions to be measured both when they contract and when they relax. The accuracy of this method has been checked and the measurements of the cross section of medial and inferior recti and of superior obliques can be considered to be valid. Measurements of length are inaccurate and the other muscles are not perpendicular to the sectional planes generally used in MRI of the head. By means of a fixation scale situated in the tunnel of the machine, the maximum diameter of medial recti in their thickest part was evaluated in two girls affected by a Stilling Duane retraction syndrome of the left eye. Two direction of the gaze were explored: 25 degrees at the right, then 25 degrees at the left, these angles being obtained by the fixation of particular points of the tunnel scale. The measurements have been made on axial sections, then on coronal sections, both medio-orbital and apical. The first finding is that the diseased medial rectus is much bigger than the healthy one. When relaxed, its thickness is about the same as that of the contracted normal muscle. Coronal orbital cross sections clearly show recession of the belly of the diseased muscle towards the back of the orbit. When contracted it stays in the apical plane and when relaxed in the medio-orbital plane. Lastly the relaxation is much weaker for the pathological muscle than for the healthy one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297661 TI - [Surgical treatment of major ptosis by frontal suspension with temporal aponeurosis]. PMID- 1297662 TI - [Surgical treatment of severe myopia]. PMID- 1297663 TI - [Comparative results of flowmeter studies before and after urodynamic exploration]. AB - Results of flowmeter studies in 145 patients before and then immediately after urodynamic exploration were unchanged in 80% of women and 72% of men. Abnormal results on flowmetric examination, detected in 18% of cases prior to urodynamic studies, were assessed as normal during follow-up urodynamic tests. These findings raise the question of the validity of flowmeter parameters determined during urethrocystometric exploration. PMID- 1297664 TI - [Neuropathy due to stretching of the internal pudendal nerve and female urinary incontinence]. AB - For many years, perineal neurogenic abnormalities associated with stress urinary incontinence have been described using electromyography examination, evoked potentials or neuromuscular biopsy. It has been suggested that the progressive denervation of the striated pelvic sphincter musculature that occurs in genuine stress incontinence is due to repeated stretch injury of the innervation of these muscles when the pelvic floor diaphragm is weak. New investigations such as perineal nerve motor latency confirmed this hypothesis. A real "perineal stretch neuropathy" may be described. It is very important to know about this neurogenic factor before considering rehabilitation therapy. PMID- 1297665 TI - [Treatment of strictures of the male urethra by internal urethrotomy]. AB - Seventy patients with urethral strictures underwent endoscopic urethrotomy in the Department of Urology of the Ionnina University Hospital since 1983. The mean age of the patients was 58 years and they were treated for single (53 cases) or multiple (17 cases) urethral strictures. The cause of stricture was traumatic, post-infections, iatrogenic (post-TURP or open adenomectomy) or unknown in 6, 21, 28 and 15 patients respectively. Good results were obtained after the first endoscopic urethrotomy in 36% of cases (25 patients), at 5 year follow-up. The success rate of repeated internal urethrotomies was satisfactory in 54% of cases (38 patients). Finally, 4 patients (6%) had 5 or 6 internal urethrotomies and many urethral dilatations and were then treated by urethrectomy followed by termino-terminal urethrraphy. PMID- 1297666 TI - Proper use of gastrointestinal tract to achieve continent urinary diversion in 73 patients. AB - Different segments of the gastrointestinal tract have been used to reconstruct the bladder and all have been reviewed in regard to achieving urinary continence. In 53 patients with detubularized ileocecal cystoplasty, the continence rate, both during the day and night, was 88%, while 95% of the patients were continent during the daytime. In nine patients in whom an ileocecal continent reservoir was made, 100% had dry stoma on intermittent catheterization, both during the day and night. We conclude that detubularization of the right colon has a significant effect in achieving urinary control and making a good low pressure pouch. This has helped us to avoid conduits with their inherent problems. Also, the right colon by virtue of the ileocecal valve has good versatility for use in both anti incontinence or anti-reflux procedures as needed. PMID- 1297667 TI - Urethral instability after radical hysterectomy. AB - The incidence of urethral instability after total hysterectomy for cervical cancer was analyzed in 154 patients allocated to one of two groups according to the extent of vaginal resection. Evaluations were conducted during urodynamic exploration prior to and 1 year after surgery. Persistent instability of urethra at 1 year follow-up was noted only in the group in which the resection had involved 2/3rds of the vagina, 18% of these patients being assessed as possessing urethral instability. Variations in maximum pressure greater than 30 cm H2O resulted in major clinical and urinary disorders. PMID- 1297668 TI - [Ureterovaginal fistulas: diagnosis and surgical tactic. Apropos of 19 personal cases]. AB - Personal experience of the treatment of 19 ureterovaginal fistulae, observed from september 1987 to june 1991 on 17 patients in Africa is described and analysed. Occurring after gynecological or obstetrical surgery, the main cause is hysterectomy (82.3%). Elements for diagnosis were: the appearance of a urine leak, which in most cases came rapidly, echography, and most important, intravenous urography (IVU). Surgical management in all of the cases was mainly aimed at conservation. One end-to-end anastomosis and 18 cuff reimplantations were performed, combined in 2 cases with a sub-mucus tunnel (Politano), in 14 cases combined with a tubular Boari bladder flap (wherein 1 case was bilateral), 3 combined with a bladder psoas hitch and 2 with an isolated ileal graft (ileo ureterocystoplasty). One case of vesicouterine fistula and 4 associated vesicovaginal fistulae benefited from a simultaneous surgical operation. In this study of 17 patients treated, except for one patient deceased 14 months following a neoplastic recurrence, the results were excellent. 16 patients were cured. Follow-up extended to more than a year and have shown the perfect conservation of the excretory ducts in all of the cases studied. The cuffed ureterovesical reimplantation combined with a tubular bladder plasty definitively seem to be a most reliable management technique for all ureter injury encountered. While allowing the preservation of the kidney located just below, it has, in particular, prevented ureter stenosis. If the use of simpler methods (psoas bladder hitch) may be sufficient for some cases, the use of more complex method (ileoureterocystoplasty) for other cases, may be indispensable. PMID- 1297669 TI - [Gunshot wounds of the ureter]. AB - Lesions of the ureter caused by penetrating wounds of the abdomen rare a are complication of abdominal gunshot wounds, of which the reported incidence is 2 to 17%. The preoperative diagnosis is difficult and unrecognized initially in every third case. There are no early clinical signs of ureteral lesions. There is often no hematuria. Only IVP can male the preoperative diagnosis possible. As a matter of fact, the diagnosis will often be established by the surgical exploration made during the laparotomy required by the extent of the associated lesions. The ureteral blast contusion is an important cause of secondary necrosis with fistula. The treatment is mainly based on ureteroureterostomy after debridement. The transanasmotic drainage of urine is controversial. Mortality results from associated abdominal lesions and morbidity consists in a risk of secondary nephrectomy. PMID- 1297670 TI - [Tumor of the urinary tract and renal lithiasis. Apropos of 4 cases]. AB - The authors present four observation of renal lithiasis associated with a tumor of the upper urinary tract. The rarity of this association and the facility to only consider lithiasis often conceal the tumor. They define the "high risk lithiasis" for which CT-scan is mandatory. Tumor of the urinary tract has to be treated and the prognosis becomes less favorable. PMID- 1297671 TI - [Kidney carbuncle: diagnostic, bacteriological and therapeutic considerations. Apropos of 11 cases]. AB - Renal carbuncle is a cortical lesion following bacteremia, occurring in patient without any urologic known problems. The analysis of 11 consecutive renal carbuncles showed that one should consider the diagnosis of renal carbuncle in young patients with flank pain, fever, and absence of significant leucocyturia. Our study confirms that renal carbuncle is always caused by staphylococcus aureus and that treatment is based on appropriate antibiotherapy. Isolation of the bacteria was difficult unless ponction of carbuncle under ultrasound control was performed. The usefulness of ultrasonography for the diagnosis of renal carbuncle and for its distinction from other suppurative renal lesions is emphasized. PMID- 1297672 TI - A comparison of electrocardiographic QRS changes and two-dimensional echocardiographic left ventricular wall motion predischarge and in the 4th year following first acute myocardial infarction. PMID- 1297673 TI - Myocardial salvage after reperfusion. Observations from analysis of serial electrocardiographic and biochemical indices. AB - Careful assessment of the ECG and the release patterns of biochemical markers after established reperfusion has made it possible to relate the observed changes to the degree of myocardial salvage, left ventricular function, and clinical outcomes. These observations will become increasingly important in assisting the clinician to stratify patients into different prognostic categories during acute MI treated with thrombolytic therapy. In the future, risk stratification based on noninvasive indices provided by ECG and biochemical markers will aid physicians in optimally using thrombolytic therapy. PMID- 1297674 TI - Inverse electrocardiographic transformations. Dependence on the number of epicardial regions and body surface data points. PMID- 1297675 TI - On computing pericardial potentials and current densities in inverse electrocardiography. PMID- 1297676 TI - A statistical analysis of the ECG measurements used in computerized interpretation of acute anterior myocardial infarction with applications to interpretive criteria development. AB - Computerized interpretation of the electrocardiogram (ECG) for detection of acute myocardial infarction (AMI) has been an area of active investigation for the past few years. Advances in the development of criteria for increased accuracy have resulted through the use of clinically correlated databases. Previously, using such databases, the sensitivity for interpretation of AMI in the Marquette 12SL ECG analysis program has increased from 21% to 65% with specificity remaining unchanged (99%). This study attempted to find measurements of the QRS and ST segment from 7 of the 12 standard ECG leads to increase the sensitivity of detection of anterior AMI to the level of a trained physician while maintaining the current level of specificity. Regression analyses were performed on the measurements to see which ones could improve sensitivity and what effect they had on specificity. There was no clear separation of the individual measurements between the normal database or the true positive and true negative anterior AMI databases for maintaining high specificity. In a parallel study of the same data, deterministic criteria combining both ST and T wave information increased the sensitivity of the 12SL analysis program for detection of anterior AMI to 71% on a clinically correlated anterior AMI database and 75% on a physician interpreted anterior AMI database while maintaining the specificity at 99%. PMID- 1297677 TI - Assessment of diagnostic ECG results using information and decision theory. Results from the CSE diagnostic study. AB - Information and decision theory were applied to assess the interpretation results of 15 computer programs (9 electrocardiogram and 6 vectorcardiogram) and 9 cardiologists; 8 of whom analyzed the electrocardiogram and 5 the vectorcardiogram, using a database of 1,220 clinically validated cases. The study demonstrates that information content and utility indices, by providing a comprehensive view of diagnostic performance, can enhance the insight given by the more classic statistical performance measures. PMID- 1297678 TI - Combination of diagnostic classifications from ECG and VCG computer interpretations. AB - The Common Standards for Quantitative Electrocardiography (CSE) study showed that the weighted combined diagnostic classification of a group of experts or a set of electrocardiographic (ECG) programs is superior to the average expert or program, and sometimes even better than the best expert. For that reason the authors investigated whether the combination of classifications from the authors' programs for ECG and vectorcardiographic (VCG) interpretation would deliver better results than either one separately. The CSE diagnostic database (n = 1,220) was used for testing purposes. Since the combination of computer interpretations from the ECG and VCG requires a separate and preferably simultaneous recording of the VCG, the authors also examined the combined interpretation of the ECG with a simulated VCG reconstructed from the eight independent leads of the 12-lead ECG (the rVCG). Besides that, the authors investigated the combined interpretation from all single beats of the dominant waveform from the same ECG recording (sECG). The performance of all combinations, that is, the ECG + VCG, ECG + rVCG, and sECG proved to be significantly better (74.2%, 73.6%, and 71.2%, respectively) than that of the ECG or VCG separately (69.8% and 70.2%, respectively; p < 0.001 for all cases). However, the difference in performance between the sECG and the VCG was not significant. PMID- 1297679 TI - Should the JT rather than the QT interval be used to detect prolongation of ventricular repolarization? An assessment in normal conduction and in ventricular conduction defects. AB - It has been suggested that the JT rather than QT interval properly reflects repolarization duration in ventricular conduction defects (VCD). The authors examined the influence of QRS duration on the JT and QT intervals in 20,687 normal adult subjects and 2,865 subjects with various categories of VCD. Estimates for coefficients for multiple regression of QRS duration on QT and JT intervals combined with a correction term for heart rate (HR) were determined for each VCD category. QRS duration accounted for about 16% of total QT variation, but had a practically negligible effect on JT interval in complete bundle branch blocks. A single-parameter formula was derived for the JT prolongation index of the form JTI = JT(HR + 100)/518, with a JTI > or = 112 identifying repolarization prolongation in all VCD categories. It is concluded that it is preferable to predict JT rather than QT as a more appropriate index of duration of repolarization in VCD. PMID- 1297680 TI - Quantitative assessment of 12-lead ECG synthesis using CAVIAR. AB - The objective of this study is to assess the performance of patient-specific segment-specific (PSSS) synthesis in QRST complexes using CAVIAR, a new method of the serial comparison for electrocardiograms and vectorcardiograms. A collection of 250 multi-lead recordings from the Common Standards for Quantitative Electrocardiography (CSE) diagnostic pilot study is employed. QRS and ST-T segments are independently synthesized using the PSSS algorithm so that the mean squared error between the original and estimated waveforms is minimized. CAVIAR compares the recorded and synthesized QRS and ST-T segments and calculates the mean-quadratic deviation as a measure of error. The results of this study indicate that estimated QRS complexes are good representatives of their recorded counterparts, and the integrity of the spatial information is maintained by the PSSS synthesis process. Analysis of the ST-T segments suggests that the deviations between recorded and synthesized waveforms are considerably greater than those associated with the QRS complexes. The poorer performance of the ST-T segments is attributed to magnitude normalization of the spatial loops, low voltage passages, and noise interference. Using the mean-quadratic deviation and CAVIAR as methods of performance assessment, this study indicates that the PSSS synthesis algorithm accurately maintains the signal information within the 12 lead electrocardiogram. PMID- 1297681 TI - Does amplitude of the intracardiac electrogram change with time during ventricular fibrillation? Implications for fixed gain sensing devices. PMID- 1297682 TI - Implantable pacer-cardioverter-defibrillator induced episode types and programming strategies. PMID- 1297683 TI - Dual-chamber intracardiac arrhythmia analysis. PMID- 1297684 TI - The organization of atrial fibrillation. PMID- 1297685 TI - Ventricular fibrillation detection using the evoked electrogram from the braided endocardial defibrillation lead. AB - Life-threatening consequences can be the result of inappropriate classification of ventricular fibrillation for patients with implantable cardioverter defibrillators. The objective of this study was to determine if analysis of the asynchronously paced evoked electrogram using the braided endocardial defibrillation lead could improve the detection of ventricular fibrillation. The depolarization portion of the evoked electrogram was integrated to obtain the paced depolarization integral. The results demonstrated that the mean of the paced depolarization integral, its SD, and the mean +/- SD were significantly different between sinus rhythm and ventricular fibrillation (p < 0.005, p < 0.05, p < 0.01, respectively). These results suggest that the paced depolarization integral obtained with the braided endocardial defibrillation lead could improve the specificity and sensitivity of ventricular fibrillation detection. PMID- 1297686 TI - Location and magnitude of ST changes in acute myocardial infarction by analysis of body surface potential maps. PMID- 1297687 TI - Detection of late potentials. Comparison of two commercial high-resolution ECG systems. AB - Signal-averaged electrocardiogram (SAECG) is used for detection of ventricular late potentials (LPs) in cardiac patients. As many commercial SAECG systems become available, it is essential to determine if they provide equivalent diagnostic information. Two high-resolution (Hi-Res) ECG systems (MAC-12, Marquette Electronics, Inc (MEI), Milwaukee, WI and LVP101, Arrhythmia Research Technology (ART), Austin, TX) were tested on 143 subjects (13 controls and 130 cardiac patients, 21 of whom were tested for inducible ventricular tachycardia [VT]). Late potential measurements (total QRS duration, high-frequency low amplitude signal duration, and root-mean-square voltage) obtained from the two systems were in good agreement in most of the controls and patients. Application of Multicenter criteria for the MEI system and Gomes criteria for the ART system yielded very good agreement in LP diagnosis (at least 2 parameters abnormal). The two Hi-Res systems predicted inducible VT with good accuracy. The MEI system gave slightly higher sensitivity (90% vs 70%) and specificity (91% vs 82%) than the ART system in patients tested for inducible VT. In controls, both systems gave the same specificity (92%) and the LP diagnosis agreed in all controls (100%). Although the number of patients was small, neither sensitivity nor specificity were significantly different between the two systems at p < 0.05. To conclude, MEI and ART Hi-Res systems gave very similar LP diagnoses when appropriate criteria were applied. PMID- 1297688 TI - Augmented two-channel arrhythmia detection. PMID- 1297689 TI - Validation of an adaptive software trigger and arrhythmia diagnostic algorithm. AB - The authors have developed an algorithm for the identification of arrhythmias using intracardiac atrial and ventricular leads. The algorithm is based on the rate of the depolarizations and a measure of the organization of electrical activity in each of the cardiac chambers. The most important requirement of the algorithm is to identify the occurrence of each cardiac event correctly. A robust amplitude-adaptive software trigger is developed, which accurately detects depolarizations in both chambers. With this reliable trigger the authors demonstrate the veracity of the arrhythmia identification algorithm. PMID- 1297690 TI - Fractal clustering of ventricular ectopy and sudden death in mitral regurgitation. PMID- 1297691 TI - Evolution of an automated ST-segment analysis program for dynamic real-time, noninvasive detection of coronary occlusion and reperfusion. AB - Patients in whom early and stable reperfusion through the infarct artery fails after thrombolytic treatment might benefit from further revascularization therapy. A reliable noninvasive technique able to detect both reperfusion and reocclusion would be useful to test this hypothesis. However, no such technique presently exists. ST-segment recovery analysis using continuous digital 12-lead ST monitoring has been shown to be an accurate predictor of infarct artery patency in real time. This method was dependent on a trained clinician's analysis of the recordings on a personal computer. For optimal bedside application, salient principles of this ST-segment recovery analysis were converted into algorithms and built into the ST monitor software. The essentials of these algorithms are described in this report. PMID- 1297692 TI - Advanced time-frequency methods for signal-averaged ECG analysis. AB - Frequency-domain techniques have been extensively investigated for the analysis of high-resolution electrocardiograms (ECGs), although the merit of frequency domain analysis is still subject to controversy. Time-frequency analysis methods, which estimate the frequency content of a signal as a function of time, potentially provide even more information for improved ECG analysis. Some researchers report impressive results in predicting the outcome of electrophysiologic studies using the short-time Fourier transform (spectrogram). Other time-frequency representations, such as the Wigner distribution, short-time spectral estimators, and the wavelet transform, have also been investigated. The authors present a unified overview of time-frequency representations, showing that only four classes characterize most time-frequency representations. The authors describe the advantages and drawbacks of the various approaches and speculate on their promise for ECG analysis. Very preliminary experiments in applying some of these techniques to the prediction of the outcome of electrophysiologic studies have suggested some possible new research directions. PMID- 1297693 TI - Karhunen-Loeve representation of ECG data. AB - Quantitative representation of mathematical functions or random data provides a useful and often necessary step for analyzing complex physical or physiological phenomena. In general, the representation process converts complex functions or observations into weighted combinations of simple, elementary components. Rationale for use of representation lies in the simplification of restructuring the original functions or data in terms of these basic elements, which can facilitate understanding or analysis of the phenomena under study. Representation provides a basis for feature extraction in classification problems, filtering for noise reduction, and information assessment. In this paper the author describes some of the classical representation methods and demonstrates specific implementation of the statistical representation of electrocardiographic data using the Karhunen-Loeve method. PMID- 1297694 TI - Wiener filtering of high-resolution ECGs using time-frequency representations. PMID- 1297695 TI - Risk assessment of future myocardial infarction from automated serial ECG analysis. AB - From 1980 to 1990 a cohort of 7,542 employees took part in the MARISK study. This study was designed in order to explore the utility of computerized electrocardiographic (ECG) measurements for predicting future myocardial infarction. After an initial period of annual examinations, follow-up information was collected by mailed questionnaires and obtained from 89.3% of all study participants with a median follow-up time of more than 7 years. Eighty-three participants suffered from myocardial infarction during the course of the study. Multivariate logistic regression analysis revealed that automated ECG measurements contribute significant additional information to risk estimates obtained from classical risk factors. Serial ECG analysis yields stronger risk indicators than single measurements. Results are represented via receiver operating characteristic (ROC) curves and regression coefficients, which can be used in independent applications. The results of this study indicate that it is useful to include automated serial ECG analysis in cardiovascular screening programs. It still has to be evaluated whether successful preventive measures may be based on such screening programs. PMID- 1297696 TI - Source consistency filtering. Application to resting ECGs. PMID- 1297697 TI - Robust adaptive parameter estimators in arrhythmia detection. AB - The authors consider the statistical analysis of threshold crossing intervals, as applied to estimation of tachycardia rates from intracavitary electrograms. The authors developed a class of robust algorithms designed to produce minimum variance estimates for tachycardia rates. The authors formulated the algorithms using order statistic filters, and obtained the minimum variance unbiased order statistic estimator. The potential gain in efficiency achieved by this approach is demonstrated via a representative example. The results indicated that the order statistics operator can produce dramatic reductions for typical errors in error variance as compared to linear estimators. PMID- 1297698 TI - Influence of noise on the analysis of late potentials. PMID- 1297699 TI - Problems in measuring heart rate variability of patients with congestive heart failure. AB - Heart rate variability (HRV) has become an important noninvasive measure of the integrity of the autonomic nervous system in various disease states. The power spectrum of HRV is a means to separate the instability oscillations of the various feedback mechanisms that contribute to cardiovascular homeostasis. The reliability of HRV data is largely unexplored. The day-to-day correlations in the low and mid-frequency components of HRV spectra average 91%, and that of the high frequency component averages 81%. The correlations among spectral and nonspectral measures of HRV (SD) for the same data segment average 50-60%, suggesting that they encode similar information. Heart rate variability spectra exhibit diurnal variation consistent with physiologic expectation: respiratory sinus arrhythmia (thought to be mediated by parasympathetic tone) and to a lesser extent, the low frequency spectral component (thought to be of mixed sympathetic-parasympathetic origin) are higher at night than in the daytime; the mid-frequency component (associated with the baroreflex, which is more excited when the patient is upright) is slightly higher during the daytime. Increased frequency of ectopic beats, such as occurs in congestive heart failure, reduces the reliability of the power spectrum since the number of usable data segments falls off rapidly with even small increases in rate of ectopy, and the variance of the estimate (in the method of averaged periodograms) is inversely proportional to the square root of the number of data segments. Using shorter data segments increases the number of segments available, but reduces resolution. Interpolation over ectopic beats (by either linear or cubic splint interpolation) increases the apparent power in low frequencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297700 TI - Prognostic value of heart rate variability measures in patients with chronic, nonischemic mitral regurgitation. PMID- 1297701 TI - Details of a real world implementation of Fourier techniques for power spectral analysis of heart rate variability. AB - A software package designed to perform a power spectral analysis of heart rate variability for Holter data is presented. The implementation is for the SpaceLabs Medical FT series 386/486-based Holter analysis workstation (Redmond, WA). The package is designed to allow rapid assessment of both short-term and long-term fluctuations in the heart rate spectrum. The package can be used to make a variety of spectral measurements of heart rate variability. PMID- 1297702 TI - Autoregressive spectral models of heart rate variability. Practical issues. AB - Autoregressive time series model-based spectral estimates of heart period sequences can provide a parsimonious and visually attractive representation of the dynamics of interbeat intervals. While a corollary to Wold's decomposition theorem implies that the discrete Fourier periodogram spectral estimate and the autoregressive spectral estimate converge asymptotically, there are practical differences between the two approaches when applied to short blocks of data. Autoregressive spectra can achieve good frequency resolution and excellent statistical stability on short segments of heart period data of sinus origin. However, the order of the autoregressive model (number of free parameters to be estimated) must be explicitly chosen, a decision that influences the trade-off of frequency resolution with statistical stability. Akaike's Information Criterion (AIC), an information-theoretic rule for picking the optimum order, is sensitive to the aggregate amount of data in the analysis. Thus, the best model order for estimating the spectrum of a 4-minute segment of data will generally be lower than the best order for estimating an hourly spectrum based on averaging 15 4 minute spectra. A major advantage of the autoregressive model approach to spectral analysis is the ease with which it can be extended to handle messy data frequently seen in heart rate variability studies. A number of autoregressive based robust-resistant techniques are available for the analysis of heart period sequences that contain a high volume of nonsinus and other unusual beats intervals. A theoretically satisfying framework is also available for spectral analysis of unevenly sampled data and missing data. PMID- 1297703 TI - Comparison of autoregression and fast Fourier transform techniques for power spectral analysis of heart period variability of persons with sudden cardiac arrest before and after therapy to increase heart period variability. AB - Clinical studies have used two types of analysis of the power spectral estimates of heart period variability: autoregressive and fast Fourier transform techniques. Controversy exists regarding which method is the most valid. The specific aims of this study are: (1) to describe the power spectra of heart period variability before and after an intervention designed to increase heart period variability in persons after sudden cardiac arrest; (2) to compare the integral of power spectral density between autoregressive and fast Fourier transform techniques within low and high-frequency bands; (3) to compare the magnitude of the spectral peak values determined by autoregressive and fast Fourier transform techniques approaches within low and high-frequency bands; and (4) to compare the aforementioned parameters using 4-minute, 1-hour, and 24-hour blocks of heart period data. Results indicated high correlations between spectral estimations by autoregressive and fast Fourier transform techniques using integrals or peak values within either the low or high-frequency ranges. The autoregressive technique demonstrated better resolution of sharp peaks than the fast Fourier transform technique, and makes a smoother, more interpretable curve. Lastly, people can cognitively change their heart rate variability. PMID- 1297704 TI - Electrocardiographic phasing of acute myocardial infarction. PMID- 1297705 TI - The significance of lead strength on ST changes during treadmill stress tests. AB - The contribution of relative lead strengths to ST depression during exercise was evaluated in 334 patients who had both a treadmill stress test and an angiogram. Patients were referred for exercise testing for the evaluation of suspected or known coronary artery disease. This was accomplished by comparing the magnitude of ST-segment depression to a constructed ST/R ratio. Using a cutoff of 0.1 for the ST/R ratio, the data were compared to the sensitivity and specificity of the 1 mm criteria for ST depression. There was only a slight increase in sensitivity (59% vs 63%) and specificity (60% vs 78%) for the ST/R ratio in comparison to the standard ST depression. However, when these two criteria were reevaluated for patients with less than or equal to 10.0 mm of R wave amplitude, the 0.1 ST/R ratio had a small decrease in specificity (94% vs 80%) when compared to 1 mm of ST depression and a marked increase in sensitivity with 31% for the standard ST depression and 82% using the ST/R ratio. In those with an R wave greater than 20 mm, 1 mm of ST depression was much more sensitive than the ST/HR ratio (95% vs 59%), but the ratio was more specific than the conventional ST depression (78% vs 59%). It is concluded that ST depression should be corrected for R wave amplitude in patients with R waves less than 10 mm and over 20 mm. PMID- 1297706 TI - Effect of measurement interval on performance of the ST integral for the identification of three-vessel coronary disease. AB - Measurement of the ST integral has usually incorporated ST-segment depression integrated between the J point and 80 ms after the J point (J + 80). To assess the effect of varied onset and offset of ST measurement on performance of the ST integral for the identification of three-vessel coronary disease, the exercise electrocardiograms (ECGs) of 60 patients with angiographically proven coronary disease were analyzed using J point or J + 20 onsets and J + 60 or J + 80 offsets of ST integral calculation. Simple ST-segment depression of greater than 200 microV, measured at 60 ms after the J point, identified three-vessel disease with a specificity of 68% (17 out of 25 patients) and sensitivity of 69% (22 out of 35 patients). At a matched specificity of 68% (17 out of 25 patients), there was identical sensitivity (54%, 19 out of 35 patients) of ST integrals measured either from the J point to J + 80, from the J point to J + 60, or from J + 20 to J + 60. A trend toward increased sensitivity (60%, 21 out of 35 patients) when the ST integral was measured from J + 20 to J + 80 did not reach statistical significance, and comparison of receive operating characteristics (ROC) curves demonstrated that varying the onset and offset of ST-segment measurement had no significant effect on the overall performance of ST integral criteria for the detection of three-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297707 TI - Filters for the reduction of baseline wander and muscle artifact in the ECG. AB - Contamination of the electrocardiographic (ECG) signal by extraneous electrical potentials is a significant problem in exercise electrocardiography. Baseline wander and muscle artifact are particularly troublesome sources of interference. This paper describes two digital filters that were constructed and found effective in reducing these two types of signal contamination. The baseline wander filter presented here is a linear phase high-pass filter having a cutoff frequency lower than the heart rate. The low computational overhead makes this filter practical for multiple channel implementation on a low-cost digital signal processor. Because the muscle artifact signal, generated by skeletal muscle activity, occupies the same spectrum space as the heart-generated signal, spectral filtering is not very effective in eliminating it. Described here is a time-varying filter that employs a combination of linear and nonlinear filtering techniques. PMID- 1297708 TI - Prediction of severe coronary artery disease using computerized ECG measurements and discriminant function analysis. AB - This study tested the hypothesis that discriminant function analysis of clinical and exercise-test variables including computerized ST measurements could improve the prediction of severe coronary artery disease. Secondary objectives were to demonstrate the effect of digoxin and/or resting electrocardiographic (ECG) abnormalities, and to evaluate the relative importance of ST measurements made during the recovery phase and in the three lead group areas. The design was a retrospective analysis of data collected during exercise testing and coronary angiography. The ECG data were gathered and stored in digital format on optical discs and all ST measurements were made off-line using the authors' own software. Univariate and multivariate analytic methods were used to analyze all pretest characteristics as well as hemodynamic and computerized ECG responses to exercise. A 1,000-bed Veterans Affairs Medical Center served as the setting. The study included 446 male veterans who underwent a sign or symptom limited treadmill exercise test and coronary angiography. Analysis was also performed on a subset of this population formed by excluding patients receiving digoxin or with resting ECGs exhibiting left ventricular hypertrophy or ST depression (n = 328). In the total study population, the authors derived a treadmill score using discriminant function analysis. This score included: (1) the time-slope area in lead V5 during recovery; (2) delta heart rate; (3) angina pectoris during the exercise test; and (4) presence of diagnostic Q waves on the resting ECG. This score was effective in predicting triple vessel/left main disease and outperformed exercise-induced ST depression for predicting severe coronary artery disease. After exclusion of patients with ECGs exhibiting left ventricular hypertrophy or resting ST depression and patients receiving digoxin, discriminant function analysis chose: (1) the time-slope area in lead V5 during recovery and (2) delta heart rate. Exclusion of these patients resulted in a nonsignificant decrease in specificity of all ST criteria. ST-segment amplitude or slope in lead V5 at 3.5 minutes in recovery clearly outperformed the maximal exercise measurements in both groups. Summing the depressions or selecting the most depression in the three areas (ie, lateral-V5, inferior-II, anterior-V2) did not improve test performance. Leads other than V5 did not contain significant diagnostic information. A quantitative approach to exercise testing using discriminant function analysis enhanced the tests' performance for predicting severe coronary disease. The inclusion of patients taking digoxin or with resting ECG abnormalities nonsignificantly decreases the specificity of all ST criteria.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297709 TI - Twenty-two site precordial ST mapping. Cold pressor test to detect myocardium at risk in the perioperative period. PMID- 1297710 TI - Biochemical markers of early reperfusion. PMID- 1297711 TI - Description of cardiac sources in anisotropic cardiac muscle. Application of bidomain model. AB - If the anisotropy ratios of the inner and outer domains of the myocardium are equal, then the volume distribution of cardiac sources can be replaced by an appropriate double layer on the heart surface. For an intramyocardial electrode there is an additional term proportional to the transmembrane potential. PMID- 1297712 TI - Model simulations of the action potential and electrical activity of the mammalian ventricular cell. PMID- 1297714 TI - A possible subcellular structure based on the macroscopic cardiac source. PMID- 1297713 TI - Propagation of activation in cardiac muscle. AB - The hypothesis of local circuit current flow underlying propagation of activation in cardiac muscle has been extensively documented by one-dimensional and two dimensional simulation studies. The assumptions of spatially uniform membrane capacitance and membrane ionic properties yield simulation results that are in good agreement with experimental observations in healthy cardiac muscle, thereby indicating that differences in propagation velocity and action potential upstroke between longitudinal and transverse directions can be explained solely on the basis of anisotropic intercellular coupling. Two-dimensional model studies of anisotropic propagation have also stressed the more efficient charging of the membrane capacitance and higher safety factor of propagation in the transverse direction. These conditions favor the occurrence of longitudinal unidirectional block and the initiation of reentry via transverse propagation. The authors simulated rotating waves initiated by properly phased transverse and longitudinal plane waves in a two-dimensional sheet model. Sustained propagation requires a minimum anisotropy ratio, corresponding to a velocity ratio of about 4:1. It was found, for uniform anisotropy, that the central focus wandered slightly. A higher anisotropy ratio favors a more stable rotating pattern and a more restricted movement of the central focus. PMID- 1297715 TI - Implicit and explicit constraints in inverse electrocardiography. AB - This paper reviews the major distributed source models that have been postulated over the years to support the interpretation of observed body surface potentials: double-layer models, the source description in terms of epicardial (ie, pericardial) potentials, and its equivalent: the distributed monolayer. This includes a presentation and discussion of a source model that has been developed over the past decade: the uniform double-layer model. The properties of this model are contrasted to those of other distributed source models from the perspective of their inherent capacity for imposing the constraints that are essential for regularizing the involved inverse problem. PMID- 1297716 TI - Parallel computation of ECG fields. AB - A parallel implementation of a finite difference model for computing the electric field of cardiac sources is presented. On a relatively inexpensive SIMD parallel computer, a full-forward solution is obtained in minutes, using accurate thoracic detail including anisotropy if required. Because the computation is based on a volume grid with constant size voxels, it readily accepts anatomical data from classified magnetic resonance imaging scans. By using a variation of the colored successive over-relaxation iteration, our finite difference model takes full advantage of the performance of massively parallel computers. Evaluations of the accuracy and performance of the model show the practicality of using specific anatomical models to recover the electrocardiographic field distributions for individual subjects. A relatively modest parallel machine is capable of assembling and computing a specific direct inverse solution from body surface potentials within an hour of measurement, assuming the magnetic resonance imaging classification has been previously completed. PMID- 1297717 TI - Biosynthesis and functions of glutathione, an essential biofactor. PMID- 1297718 TI - Molecular cloning of cDNAs encoding vitamin D3 25-hydroxylase and 25 hydroxyvitamin D3 24-hydroxylase. PMID- 1297719 TI - Vitamin B12(cobalamin) contents of serum and organs in various diseases and its clinical significance. PMID- 1297720 TI - Effects of methyl vitamin B12 on sperm quality. PMID- 1297721 TI - Diabetic neuropathy and vitamin B12. PMID- 1297722 TI - Sleep-wake rhythm disorders and vitamin B12. PMID- 1297723 TI - New approaches to the diagnosis of cobalamin (Cbl, vitamin B12) deficiency in neuropsychiatric disorders. PMID- 1297724 TI - Reactivities of mammalian lipoxygenases with various polyunsaturated fatty acids. PMID- 1297725 TI - The effects of fish oil on glucose transport systems. PMID- 1297726 TI - Clinical and epidemiological study of eicosapentaenoic acid (EPA) in Japan. PMID- 1297727 TI - Cardiovascular effects of N-3 fatty acids. PMID- 1297728 TI - n-3 fatty acids: biochemical actions in cancer. AB - A number of reports indicate that fish n-3 PUFA inhibit the development, growth and progression of several experimental tumors. There emerges a pattern of complex and diverse biochemical actions of n-3 PUFA in different animal tumor models, from the studies undertaken to date to evaluate the underlying mechanisms. These findings, along with the recent epidemiological evidence of an inverse correlation between fish intake and incidence of some human cancers, makes it worthwhile to determine the role of n-3 PUFA in cancer. PMID- 1297729 TI - Docosahexaenoic acid is an essential nutrient in the nervous system. PMID- 1297730 TI - Role of vitamin C in basement membrane synthesis and cell differentiation. PMID- 1297731 TI - Bioavailability and biological activity of L-ascorbic acid 2-O-alpha-glucoside. AB - AA-2G is a new stable derivative of AsA which is efficiently synthesized by regioselective transglucosylation with alpha-glucosidase and CGTase. AA-2G serves as a vitamin C supplement in experimental animals. AA-2G is easily hydrolyzed in vivo by alpha-glucosidase and also synthesized as a metabolite under some specified conditions. AA-2G stimulates collagen synthesis in cultured fibroblasts and enhances antibody production in cultured splenocytes. AA-2G which has no cytotoxicity is a promising AsA derivative for medical and nutritional uses. PMID- 1297732 TI - Nutritional significance of ascorbic acid for the metabolism of xenobiotics and cholesterol in ODS- and conventional rats. PMID- 1297733 TI - Ascorbic acid and reaction kinetics in situ: a new approach to vitamin requirements. PMID- 1297734 TI - Recommended dietary allowance: support from recent research. AB - Increasing evidence is accumulating that a synergistic role of the so-called antioxidant vitamins (C, E, beta-carotene) may have a dominant role in the prevention of cancer, cardiovascular diseases and cataract formation. Controversy still exists regarding the optimum intake of vitamin C. This is partly due to lack of accurate and easily accessible health-relevant end-points, and lack of knowledge of the role of vitamin C in biochemical functions. Today, it is clearly recognized and broadly accepted that optimal health is a consequence of dietary optimization. Attainment of optimal health rather than prevention of deficiency symptoms is the goal. There can be little doubt that in this respect the requirements for vitamin C are greater than the amount required for the mere prevention of overt or classical scurvy. The recommendation of varying levels of requirement could overcome the controversy. The following is therefore proposed: The lowest level is that value which prevents deficiency symptoms. The second level is valid for healthy populations (< 200 mg/d). This level would take into account needs which differ according to age, sex, physical activity, physiological status (e.g. pregnancy or lactation) and environmental factors such as smoking, pollution and alcohol intake. Finally, a third level should be determined for the prevention of the above-mentioned non-communicable diseases. These diseases are an important cause of disability, resulting in costs of billions of dollars annually in medical costs. Many of the above-mentioned diseases can be prevented by supplementation with vitamin C. Medical costs could thereby also be dramatically reduced. PMID- 1297735 TI - Vitamin E and atherosclerosis: an overview. PMID- 1297736 TI - Role of lipid peroxidation and antioxidants in atherogenesis. PMID- 1297737 TI - Prevention of aortic calcification in patients on hemodialysis by long-term administration of vitamin E. AB - The effects of vitamin E on the progress of atherosclerosis in patients on hemodialysis was investigated clinically using ACI. There was a significant suppression of the increase in ACI in group A, compared to group B, at the time of observation in each year. On the other hand, no significant changes were noted in BWD, CTR, BP and blood chemical examination, except that the level of MDA was significantly decreased in group A as compared with that in group B 4 years later. Since ACI is an index representing atherosclerosis, the results of this study seemed to suggest that the progress of atherosclerosis was suppressed by long-term administration of vitamin E in patients on hemodialysis. PMID- 1297738 TI - Alpha-tocopherol: a potent inhibitor of platelet adhesion. AB - Administration of vitamin E in doses of 400 IU/day exerts a potent inhibition of platelet adhesion as measured in a laminar flow chamber. Adhesion to all surfaces tested was reduced and appeared to be related to a limited pseudopodia formation in alpha-tocopherol-enriched platelets. PMID- 1297739 TI - Atherosclerosis from a viewpoint of arterial wall cell function: relation to vitamin E. AB - Vitamin E affects many key events in atheromatous lesions. Inhibition of EC injury and platelet aggregation was already reported. Foam cell formation must be inhibited according to the data presented by us and other speakers. However, effects on cell proliferation of SMC are paradoxical. The in vivo effects will be dependent on the effective concentration of vitamin E in the loci. PMID- 1297740 TI - Lipid peroxidation, vitamin E, and cardiovascular disease. PMID- 1297741 TI - A prevention trial on cerebral infarction with dl-alpha-tocopheryl nicotinate- rationales for trial. The Alpha-Tocopheryl Nicotinate Prevention Study Group. PMID- 1297742 TI - Uptake and metabolism of 4'(N)-substituted pyridoxamines by cells from the liver and kidneys of rats. PMID- 1297743 TI - B6-enzymes participating in D-amino acid metabolism. PMID- 1297744 TI - Aspartate aminotransferase of E. coli: effects of site-directed mutagenesis on substrate recognition. AB - R292 is crucial for both the binding and the catalysis of the transamination reaction of dicarboxylic acid substrates. Substitution of R292 to uncharged residues greatly enhanced the catalytic efficiency of transamination of neutral amino acids without any effect on the binding. Residues at position 292 may not be involved in recognition of the neutral side chain. The indole ring of W140 not only regulates the rotational movement of the coenzyme ring during catalysis, but it also may be involved in binding the carboxyl side chain of dicarboxylic substrates. The phenol group of Y70 is essential for the stabilization of the transition states with all substrates. Benzene ring at position 70 is necessary to recognize the glutamate-2-oxoglutarate substrate pair. PMID- 1297745 TI - Role of the active vitamin D metabolite and 1 alpha-hydroxylated analogs in the treatment of postmenopausal osteoporosis. PMID- 1297747 TI - Microbial production of vitamins and biofactors: an overview. PMID- 1297746 TI - Aging of the brain and vitamin E. AB - Using a recently-developed membrane lipid peroxidation (MLP) system, we demonstrated the important role of vitamin E in the prevention of MLP and the possible relationship between MLP and pathogenesis of Parkinson's disease. PMID- 1297748 TI - beta-Carotene production using algal biotechnology. PMID- 1297749 TI - Microbial process of menaquinone production. PMID- 1297750 TI - Production of polyunsaturated fatty acids by microorganisms. PMID- 1297751 TI - Microbial production of vitamin B2. PMID- 1297752 TI - Biotin production by using recombinant DNA technology. PMID- 1297753 TI - Biological roles of mono- and poly(ADP-ribosyl)ation. PMID- 1297754 TI - Carotenoids and tocopherols as antioxidants and singlet oxygen quenchers. PMID- 1297755 TI - Endogenous arginine-specific ADP-ribosyltransferases and target proteins. AB - We investigated vertebrate arginine-specific ADP-ribosyltransferases and target proteins for the enzyme. ADP-ribosyltransferase found in each organelle ADP ribosylated preferentially an endogenous acceptor protein co-localized with the enzyme. We propose that the ADP-ribosylation of tissue-specific target protein by the endogenous ADP-ribosyltransferase may participate in the regulation of cellular processes, including signal transduction. PMID- 1297756 TI - The small G protein superfamily--possible functions and modes of action. PMID- 1297757 TI - Biomodulators of glucocorticoid: amplifiers and suppressors of glucocorticoid action. AB - We have found several compounds that specifically modulate the action of glucocorticoid in vivo and in vitro without themselves having any glucocorticoid like action and have proposed the concept of "Glucocorticoid Action Biomodulators". These biomodulators consist of "Glucocorticoid Sensitivity Amplifier" (GSA), "Glucocorticoid Potency Amplifiers" (GPAs), and suppressors of glucocorticoid action. GSA increased the incorporation of glucocorticoid into the liver and its binding to cytosol receptor without changing the total receptor concentration in liver cytosol and the equilibrium constant of the glucocorticoid binding reaction. GPAs, potent activators of protein kinase C, markedly enhanced the glucocorticoid action and the glucocorticoid action was inhibited by the inhibitors of protein kinase C. H-7, an inhibitor of protein kinase C, inhibited the translocation of glucocorticoid-receptor complex into nuclei without affecting the extent of phosphorylation of glucocorticoid receptor. These findings suggest that GPA(s) and the suppressors modulate some protein(s) which regulates the translocation of glucocorticoid receptor into nuclei. PMID- 1297758 TI - The relationship of protein nutrition to protein turnover. PMID- 1297759 TI - Thiamin pyrophosphate: catalytic mechanism, role in protein turnover. PMID- 1297761 TI - Role of ginsenosides as bioreactor in lipid metabolism. PMID- 1297760 TI - Cystatins as regulators of intracellular proteolysis. PMID- 1297762 TI - Role of substrate in catecholamine-induced lipolysis in rat fat cells. PMID- 1297763 TI - Vitamins and carcinogenesis: an overview. AB - The pathophysiology of carcinogenesis as a multistage process has been reviewed and the rationale for the action of vitamins and biofactors has been presented. This overview will now be followed by presentations of the actions of retinoids, carotenoids, vitamin D and marine natural products by other members of this Symposium. PMID- 1297764 TI - Carotenoids in cancer chemoprevention and therapeutic interventions. AB - Carotenoid (CARs: beta-carotene BC and/or canthaxanthin CX) supplementation have been shown to be chemopreventive in animals, since 1980, against direct or indirect chemical carcinogenesis/photo-carcinogenesis of the skin, breast, stomach, salivary glands, colon-rectum, urinary bladder, and against transplanted tumors. This action could be either independent of or dependent on pro-vitamin A activity of BC. In vitro, both BC and CX proved to be antimutagenic and to have anti-malignant transformation properties in cell cultures. Preliminary interventions in humans with BC +/- CX prevented the onset of second primary tumors in lung, colon, urinary bladder, and head and neck. The powerful antioxidant properties of CARs, possibly associated with their retinoid potential, played a role in all the above observations, producing free-radical quenching and immunostimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297765 TI - Suppression of colonic carcinogenesis by vitamin D in rats. PMID- 1297766 TI - Marine natural products against tumor development. AB - This review article deals with significant effects of marine natural products in carcinogenesis, namely as chemical probes to understand the process of carcinogenesis and as possible cancer preventive agents in humans. PMID- 1297767 TI - Microorganisms in vitamin and biofactor research. PMID- 1297768 TI - Receptor for granulocyte colony-stimulating factor. PMID- 1297769 TI - Thiamin transport in yeast and some aspects of its regulation. PMID- 1297770 TI - Some aspects of thiamin transport in mammals. PMID- 1297771 TI - Thiamin triphosphate synthesis in animals. AB - All the evidence obtained indicates that the synthesis of TTP in vitro and in vivo is catalyzed by cytosolic adenylate kinase. Further studies should explore whether adenylate kinase is the only enzyme involved in TTP synthesis, together with physiological roles of TTP in living organisms. PMID- 1297772 TI - Thiamin pyrophosphate binding mechanism and the function of the aminopyrimidine part. AB - Besides the pyrophosphate group, acting as the essential and primary binding function of TPP the N1-atom of the aminopyrimidine component functions as a second and also essential anchor to the protein component. Only if both of the contacts are formed the productive conformation of TPP within the active site of TPP enzymes is realized. A mechanism is proposed, which explains the results of our experiments with TPP-analogs. PMID- 1297773 TI - Molecular genetic aspects of human pyruvate dehydrogenase and its defect. AB - Genomic clones encompassing the entire genes for the human pyruvate dehydrogenase alpha and beta subunits (PDH alpha or beta) have been isolated by screening the leukocyte genomic libraries with a nick-translated human foreskin fibroblast PDH alpha or beta cDNA probe. These genomic clones were characterized by restriction enzyme analysis. extensive DNA sequencing and primer extension analysis. The PDH alpha gene spans 17.08 kilobases and is composed of 11 exons and 10 introns within its coding region. The 18-kilobase clone of PDH beta gene is composed of 10 exons and 9 introns. All intron-exon splice junctions of two genes follow the GT/AG rule. A total of seven Alu repeats in the PDH alpha gene were found in five introns and two Alu family in the PDH beta gene were found in intron 2 and 8. The 5'-flanking region of the PDH alpha gene contains typical CCAAT and TATA-like consensus promoter sequence and two Sp1 binding sequences. That of the PDH beta gene contains a TCAAT sequence but no TATA sequence. Primer extension analyses indicated that the PDH alpha and beta genes transcription start sites are thymine and adenine residues located 124 and 132 bases upstream from initiation codon in exon 1, respectively. Genomic DNA of patient, died 93 hours after birth with acidemia and defect of PDH activity, was isolated and all of the exons of PDH alpha and beta genes were amplified by PCR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297774 TI - How and why are some riboflavin coenzymes covalently attached to proteins? AB - Covalent flavinylation as elucidated by the formation of the histidyl(N3)-8 alpha flavin bond in 6-hydroxy-D-nicotine oxidase of A. oxidans proceeds by an non enzymatic mechanism. Incubation of the apoenzyme, FAD and a three-carbon phosphate ester at neutral pH leads to the formation of an enzymatically fully active holoenzyme. The role of His71 in this process was illustrated by site directed mutagenesis. Nevertheless, the question whether covalent attachment of the cofactor in a holoenzyme has prevailed throughout the evolutionary screening process because of biological significance or whether it is a chance event of neutral selective value is still open. PMID- 1297775 TI - Thiamin and Alzheimer's disease. AB - Because of clinical and neuropathological overlap between the characteristics of dementia of the Alzheimer type (DAT) and of a human thiamin deficiency syndrome (Wernicke-Korsakoff syndrome), thiamin pyrophosphate (TPP) dependent processes have been studied in DAT brain and other tissues. The activities of 3 TPP dependent enzymes are reduced in DAT brain: transketolase (TK), the pyruvate dehydrogenase complex (PDHC), and the alpha-ketoglutarate dehydrogenase complex (KGDHC). Quantitatively, the most marked reductions are in KGDHC (to less than 20% of normal). In cultured skin fibroblasts, KGDHC activity is reduced to 50-60% of normal, TK activity to 80-90% of normal, and PDHC is normal. Structural and molecular studies of the DAT and non-DAT enzymes are in process. A lesion of KGDHC may be related to the pathogenesis of DAT. Treatment with large doses of thiamin has not been beneficial, but the data are not totally negative. Further studies of thiamin-dependent mechanisms in DAT seem justified. PMID- 1297776 TI - Specificity of the vitamin K and glutamyl binding sites of the liver microsomal gamma-glutamyl carboxylase. PMID- 1297777 TI - Pathogenesis of vitamin K deficiency in newborn infants. PMID- 1297778 TI - Comparative aspects of human vitamin K metabolism and nutriture. PMID- 1297779 TI - Serum and liver concentrations of vitamin K in surgical patients. PMID- 1297780 TI - Pathogenesis of hypoprothrombinemia induced by antibiotics. PMID- 1297781 TI - The roles of intestinal flora and intestinal function on vitamin K metabolism. PMID- 1297782 TI - Bioavailability of vitamins--an overview. PMID- 1297783 TI - Changes in plasma levels of vitamin D and its metabolites in healthy subjects after oral administration of vitamin D2. PMID- 1297784 TI - Blood levels and urinary excretion of thiamin and riboflavin during oral administration of multivitamin tablets to healthy adults. AB - 1. The baseline blood thiamin concentration increased gradually during the long term administration of TTFD, and the blood concentration was dose-dependent. The cumulative urinary thiamin excretion showed the same dose-dependence as the blood concentration. 2. The baseline blood riboflavin concentration also increased steadily during the administration period, but the increase was less than that of thiamin. Dose-dependence of the cumulative urinary excretion of riboflavin was noted. 3. No side effect were observed. PMID- 1297785 TI - Some considerations in the pharmacokinetic analysis of vitamins. PMID- 1297786 TI - Vitamin C bioavailability. AB - The above brief review indicates that the bioavailability of vitamin C in humans is complex and that our current understanding of that process and factors that influence it are incomplete. It is important that an overall pharmacokinetic scheme be developed and tested to completely describe the complex dispositional and absorption processes of the vitamin. Such information will provide a better understanding of the absorption and disposition of the vitamin per se. Furthermore, that information will permit us to better understand how those factors influence the participation of the vitamin in events associated with maintenance of health. PMID- 1297787 TI - The lipoyl domain and its role in thiamin diphosphate-dependent oxidative decarboxylation. PMID- 1297788 TI - Biochemical and molecular genetic aspects of eukaryotic pyruvate dehydrogenase multienzyme complexes. AB - The alpha-keto acid dehydrogenase multienzyme complexes play central roles in metabolism, are major sites of regulation, and are clinically important. Genes and cDNAs encoding the components of these complexes have been cloned and sequenced. Protein engineering and molecular cloning experiments are providing new insight into organization, structure-function relationships, and the molecular basis of genetic defects in these multienzyme complexes. PMID- 1297789 TI - Chemical spectroscopic and crystallographic studies of UDP-galactose 4-epimerase from Escherichia coli. PMID- 1297790 TI - Structure and function of thermostable amino acid dehydrogenases. PMID- 1297791 TI - Recent advances in carotenoid studies--metabolisms and bioactivities. PMID- 1297792 TI - Function of vitamin A in normal and malignant leukocytes. PMID- 1297793 TI - Retinoic acid regulates the expression of a new heparin binding growth differentiation factor. PMID- 1297795 TI - Novel aspects of metabolism and function of tetrahydrobiopterin. PMID- 1297796 TI - Role of enzymes in tetrahydrobiopterin biosynthesis: computer analysis of the sequential reaction of the last step. AB - Computer simulation analysis of the experimental data showed that Cl'-keto PH4 and C2'-keto PH4 were sequential intermediates of the reduction of PPH4 to BH4 by SPR and that the reaction in the last step of the BH4 biosynthesis proceeds as follows: PPH4-->Cl'-keto PH4-->C2'-keto PH4-->BH4 Cl'-keto PH4 is not detectable in the reduction of PPH4 by the purified SPR at neutral pH since isomerization (- >) [8] may occur far more rapidly than the first reduction (-->). PMID- 1297794 TI - Neuronal differentiation of human neuroblastoma cells by retinoid. PMID- 1297797 TI - 7-substituted pterins: formation and occurrence. PMID- 1297799 TI - Zinc: brain maturation and function. PMID- 1297798 TI - 6R-tetrahydrobiopterin biosynthesis: structures of rat and human sepiapterin reductase. PMID- 1297800 TI - Zinc status in proliferative response of T lymphocytes. AB - The in vitro proliferation of T lymphocytes are highly susceptible to Zn deprivation and Cd addition. In order to define Zn status in T cell proliferation, toxicological and biochemical situation of Zn in proliferative response of T cells was investigated by use of mouse spleen cell cultures stimulated by T cell-mitogen, Con A. The inhibitory effect of Cd on T cell proliferation was protected specifically by Zn. The protection by Zn was effective when Zn was added within 16 h after Con A stimulation. Zn addition affected neither Cd content in cells nor induction of Cd-thionein. These findings indicate that Zn-dependent processes expressed before the S phase of cell cycle are critical for T cell proliferation and are targets susceptible to Cd. Moreover, electrophoretical analysis showed two unknown Zn-binding proteins (49 and 100 KD) induced in spleen cells incubated with Con A and radioactive Zn. These Zn-binding proteins may be associated with the Zn-dependent processes critical for T cell proliferation. PMID- 1297801 TI - Membrane transport of folate compounds. AB - All eukaryotic cells and some prokaryotes that are unable to synthesize folic acid utilize membrane-associated transport systems for acquisition of the pre formed vitamin or its coenzyme forms from external sources. These transport systems, in addition to providing folates essential for cell replication, are also important because of their role in the internalization of antifolates such as Methotrexate (MTX) that are used extensively in cancer chemotherapy. Information about the components and mechanism of folate transport systems has been derived, in large part, from studies with Lactobacillus casei and L1210 mouse leukemia cells, which serve as convenient models for prokaryotes and eukaryotes, respectively. L. casei contain a single folate transport system whose Kt value (i.e., concentration for half-maximum rate of uptake) for the preferred substrate folate is in the nanomolar range. The hydrophobic membrane-associated folate transport protein (18 kDa) has been purified to homogeneity and characterized. Expression of this transporter is repressed in cells grown on high concentrations (microM) of folate. L1210 cells contain two separate transport systems for folate compounds: (1) the low affinity system (Kt values for the preferred substrates 5-methyl- and 5-formyltetrahydrofolate and MTX in the microM range); and (2) the high affinity system (Kt for folate in the nM range). Fluorescein and biotin derivatives of MTX and folate, after conversion to N hydroxysuccinimide esters, can be attached covalently to the transporters. These probes have been used for visualizing the transporters by fluorescence and electron microscopy and for their purification to homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297802 TI - Role of zinc as an activator of bone formation. PMID- 1297803 TI - Zinc status in liver and gastrointestinal diseases. PMID- 1297804 TI - Role of zinc in surgical nutrition. AB - Redistribution of zinc in tissues was induced during zinc-free TPN in PEM, and a marked decrease in skin zinc level may contribute to skin lesions and to impaired wound healing in skin. And clinical studies suggest that plasma zinc level is one of the sensitive markers for stress following surgery. PMID- 1297805 TI - Zinc in pediatric surgery. PMID- 1297806 TI - Free radical pathology and antioxidants: overview. PMID- 1297807 TI - Free radical-induced biological damage and the critical roles of vitamin A, vitamin C, vitamin D and vitamin E and of copper, iron, selenium and zinc. PMID- 1297808 TI - Theoretical basis for antioxidant action in disease prevention. PMID- 1297809 TI - The mode of action of lipid-soluble antioxidants in biological membranes. Relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles. AB - The effects of ubiquinol and vitamin E on ascorbate- and ADP-Fe(3+)-induced lipid peroxidation were investigated in beef heart submitochondrial particles before and after extraction of ubiquinone and vitamin E, and after reincorporation of either or both of these components. It is concluded that ubiquinol is capable of inhibiting lipid peroxidation without the mediation of vitamin E, but may also amplify the antioxidant effect of the latter. It is pointed out that ubiquinol is the only known lipid-soluble antioxidant that can be synthesized de novo in animal cells, and for which there exists an enzymic mechanism--the mitochondrial electron-transport system--that can regenerate the antioxidant from its oxidized form resulting from its inhibitory effect on lipid peroxidation. These features, together with its high degree of hydrophobicity and its general occurrence in biological membrane and in low-density lipoprotein, suggest a highly important role of ubiquinol in cellular defense against oxidative damage. PMID- 1297810 TI - Antioxidant function of coenzyme Q. AB - Evidence for in vivo antioxidative activity of reduced CoQ homologs has been presented. This came from studies with experimental endotoxemia in mice, reoxygenation of rat liver following ischemia, and reoxygenation of canine heart following 24-hour cold preservation. In radical-induced injury of hepatocytes, it has been first shown that reduced CoQ9 acts as a potential antioxidant regardless of its cellular concentration, whereas reduced CoQ10 acts in cells containing CoQ10 as the predominant homolog. The antioxidant activity of reduced CoQ homologs appears to be independent of that of alpha-tocopherol under the conditions employed. PMID- 1297811 TI - Antioxidants in gastric mucosal injury. PMID- 1297812 TI - beta-Carotene and disease prevention. AB - Cancer and cardiovascular disease are still the number one and two killer diseases in most developed countries. There is justified hope that beta-carotene will be proven efficacious in the prevention and/or delaying of the onset of these chronic diseases. Chronic disease prevention through better nutrition, judicious use of supplements and better lifestyles will assume added importance in the coming years as the proportion of the population over 65 years increases. PMID- 1297813 TI - Future prospects. PMID- 1297814 TI - Structure of monoaminergic neuron systems in the brain. PMID- 1297816 TI - Diurnal monoamine variation in young and old rats: a microdialysis study. AB - The levels of striatal extracellular DA, DOPAC, HVA and 5-HIAA significantly decreased in aged rats compared to young adults. The magnitude of age-related reduction was greater in dopaminergic than serotonergic substances. The levels of striatal extracellular monoamines in young adult rats showed significant diurnal variations. On the other hand, these substances of aged rats, except for HVA, did not exhibit significant diurnal variations. Enriched environment housing increased levels of striatal extracellular DOPAC in aged rats, but did not influence on the age-related changes of diurnal variations in the striatal extracellular monoamines. PMID- 1297817 TI - Biosynthesis and functions of selenoenzymes. PMID- 1297815 TI - Brain histamine: psychoneuroimmune regulator in physiological and pathological conditions. AB - HA is a biogenic amine widely distributed in the CNS, with neurons located in the posterior hypothalamus. HA acts as a neurotransmitter and/or neuromodulator regulating neuroendocrine and neuroimmune functions, circadian rhythms, sleep wakefulness cycle, body temperature, centrally-mediated neurovegetative functions, cerebrovascular control, and behavior and learning. Changes in brain HA are observed in aging. High levels of HA in CSF and CNS of AD patients might reflect a reactive response to neuroimmune activation and tissue damage. PMID- 1297818 TI - Thiamine responsive pyruvate dehydrogenase deficiency. AB - We studied a PDH deficient patient who is clinically responsive to thiamine. High Km and low Vmax values for the TPP were identified in the patient's cultured cells. Immunoblot analysis detected trace amount of mutant E1 alpha polypeptide which was 3.5 KD larger than normal in size. Four-nucleotide deletion in the E1 alpha gene causes a reading frame shift, producing an abnormal polypeptide with additional 31 amino acids at C-terminus of the E1 alpha subunit. The tryptophan (codon 383) and lysine (385) residues near the C-terminus might play a crucial role in the binding of TPP to the E1. PMID- 1297819 TI - Pyridoxine responsive and unresponsive homocystinuria. PMID- 1297820 TI - Vitamin B12 (Cbl)-responsive disorders. PMID- 1297821 TI - Neonatal form of biotin-responsive multiple carboxylase deficiency. PMID- 1297822 TI - Biopterin-responsive hyperphenylalaninemia. PMID- 1297823 TI - Vitamin E status in children-health and diseases. PMID- 1297824 TI - The family of protein kinase C in transmembrane signalling for cellular regulation. AB - Signal-induced hydrolysis of inositol phospholipid produces two second messengers, diacylglycerol and inositol trisphosphate. Diacylglycerol activates protein kinase C, whereas inositol trisphosphate mobilizes Ca2+ from its internal store. Analogously, signal-induced hydrolysis of choline phospholipid generates two second messengers, unsaturated free fatty acid and lysophosphatidylcholine. The free fatty acid synergizes with diacylglycerol to activate protein kinase C and causes full activation of the enzyme even at the basal level of Ca2+. On the other hand, lysophosphatidylcholine dramatically enhances cellular responses such as cell proliferation and differentiation under the conditions where diacylglycerol and Ca2+ are available. It is likely that all of the immediate products of signal-induced degradation of inositol and choline phospholipids are involved directly in concert in the transmembrane control of cellular functions. PMID- 1297825 TI - 1,25-Dihydroxyvitamin D3 regulation of cell replication and differentiation. PMID- 1297826 TI - Further metabolism of 1 alpha,25-dihydroxyvitamin D3 in target cells. AB - Calcitriol-inducible C-24 oxidation in target cells gives rise to calcitroic acid in a variety of cells. The pathway probably involves a transient C23-aldehyde intermediate. The pathway appears to play a crucial role in the duration of the 1,25-(OH)2D3 signal in target cells. New analogs can be designed to render the molecule more susceptible or more resistant to target cell catabolism. However, these changes do not guarantee survival of the drug due to alternative degradatory pathways. PMID- 1297827 TI - Evolutionary biology and pathology of vitamin D. AB - There is mounting evidence that essentially all fungi, plants and animals living on earth produce provitamin D. It is likely that once exposed to sunlight, these provitamins are converted to previtamin D. It is unclear why fungi, phytoplankton, zooplankton and plants have the capacity to produce such large quantities of provitamin D. It is likely, however, that provitamin D and possibly vitamin D play an important biologic role in these organisms. Buchala and Schmid found, for example, that vitamin D3 promoted adventitious root development. It may be that provitamin D has a more fundamental function in lower life forms. Provitamin D and its photoproducts have UV absorption spectra that overlap with the ultraviolet absorption spectra from ultraviolet radiation-sensitive macromolecules including DNA, RNA and proteins. Thus, provitamin D and photoisomers could serve as a photon sink, and therefore, act as a natural sunscreen to protect lower life forms from the damaging effects of the high energy ultraviolet radiation that they are exposed to. It is more clear, however, that amphibians, reptiles, birds, mammals and humans all require vitamin D and that the vitamin D must be metabolized to 1,25(OH)2D3 before it can carry-out its physiologic functions on calcium and bone metabolism. The intense research activities during the past decade on the antiproliferative and differentiation activities of 1,25(OH)2D3 has opened a new chapter for this vitamin/hormone. 1,25(OH)2D3 and its analogs are being developed for the treatment of psoriasis, breast cancer, and leukemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297828 TI - 1,25-Dihydroxyvitamin D3 for the treatment of psoriasis. PMID- 1297829 TI - Tissue-specific production of the third component of complement(C3) by vitamin D in bone. AB - The third component of complement (C3) is a protein produced by osteoblastic cells in response to 1 alpha,25(OH)2D3. The bone C3 appears to be involved in differentiation of bone marrow cells into osteoclasts in concert with other vitamin D-dependent factors. Further studies are needed to understand the precise role of C3 in bone. PMID- 1297830 TI - Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current. AB - 1. The mechanism of action of oxytocin on vagal neurones of the rat was studied using single-electrode voltage-clamp recordings from brainstem slices. The ionic basis of the oxytocin-induced current was examined by changing the composition of the perfusion solution and by making use of channel blockers. 2. In neurones clamped at or near their resting potential, oxytocin generated a sustained, TTX insensitive inward current whose peak amplitude was concentration related. This current was detectable at 10 nM, was half-maximal at about 100 nM and was maximal at micromolar concentrations of peptide. 3. The oxytocin current was inward over membrane potentials ranging from -110 to -20 mV and was voltage dependent, since it increased in magnitude as the membrane was depolarized from the resting potential toward less negative potentials. 4. Partial replacement of extracellular sodium by equimolar N-methyl-D-glucamine reversibly attenuated or suppressed the oxytocin current. By contrast, substituting part of extracellular chloride or blocking calcium currents did not modify it. Increasing the transmembrane potassium gradient was also without effect and none of the potassium channel blockers TEA, 4-amino pyridine (4-AP), apamin, caesium or barium affected the oxytocin current. This current is thus at least in part carried by sodium. 5. The activation of the oxytocin current as a function of the membrane potential could be quantitatively simulated using a Boltzmann equation, suggesting that oxytocin acts by inducing the opening of a voltage-dependent channel which can exist in either of two states, open or closed. 6. Lowering the extracellular calcium concentration from 2 to 0.1 mM, while keeping the magnesium concentration constant at 1 mM, enhanced the response to oxytocin. This low calcium-induced potentiation of the oxytocin current was 1.4-3-fold and was reversible. 7. We conclude that oxytocin increases the excitability of vagal neurones by generating a persistent, voltage-gated current which is sodium dependent, is insensitive to TTX and is modulated by divalent cations. PMID- 1297831 TI - Dynamic changes in human diaphragm length: maximal inspiratory and expulsive efforts studied with sequential radiography. AB - 1. The maximal voluntary pressure generated by the diaphragm (transdiaphragmatic pressure, Pdi) is about 50% greater during maximal expulsive efforts than during maximal inspiratory efforts against a closed airway. However, these pressures cannot be increased by interpolated phrenic stimuli in trained subjects. This suggests that variable neural drive is not responsible for the difference in voluntary pressure. To investigate whether dynamic changes in diaphragm length during inspiratory and expulsive efforts could account for this difference, we used digital sequential radiography at 6 frames per second. 2. During the development of peak Pdi in inspiratory efforts, total diaphragm length decreased by about 20% in the antero-posterior and lateral projections. During maximal expulsive efforts (with glottis open), the diaphragm shortened slightly in the early stage of pressure development but then lengthened due to contraction of abdominal muscles before peak pressure was achieved. 3. Given that force increases when a contracting muscle is lengthened (expulsive effort) and decreases during shortening (inspiratory effort), this study provides a definitive explanation for the difference in maximal voluntary pressure between pure inspiratory and expulsive efforts. PMID- 1297832 TI - Alteration of ventilatory activity by intralaryngeal CO2 in the cat. AB - 1. We investigated the responses of phrenic and hypoglossal nerve activities to the addition of 3, 5 and 10% CO2 to a constant flow of warm, humidified air through the isolated upper airway in decerebrate, paralysed, artificially ventilated cats. 2. In bilaterally vagotomized animals, intralaryngeal CO2 caused a dose-related decrease in peak integrated phrenic activity. This response became attenuated with time, but was still discernible after 3 min of continuous intralaryngeal CO2. In the same experiments, intralaryngeal CO2 caused a gradual increase in peak integrated hypoglossal nerve activity. 3. Intermittent pulsing of intralaryngeal CO2 during neural inspiration or expiration resulted in similar, but smaller decreases in the phrenic activity of some animals. Hypoglossal activity was not influenced appreciably by this procedure. 4. Systemic hypercapnia attenuated the phrenic responses to intralaryngeal CO2. The hypoglossal responses were greatly reduced or abolished. 5. In vagally intact cats, ventilated by a servo-respirator in accordance with phrenic nerve activity, intralaryngeal CO2 resulted in only a trace of reduction in phrenic discharge. After bilateral vagotomy, the same animals showed typical responses, as described above. 6. All responses to intralaryngeal CO2 were abolished after bilateral section of the superior laryngeal nerves (SLNs). 7. We conclude that intralaryngeal CO2 acts by way of receptors with afferents in the SLNs to decrease phrenic and increase hypoglossal nerve activities. The responses are not importantly gated during neural inspiration or expiration. The responses to intralaryngeal CO2 are most clearly demonstrable after bilateral vagotomy, suggesting that vagal mechanisms serve to stabilize respiratory motor neural activity in intact animals. PMID- 1297833 TI - Responses of laryngeal receptors to intralaryngeal CO2 in the cat. AB - 1. We recorded afferent activities of single fibres in the superior laryngeal nerves of decerebrate or anaesthetized, paralysed cats while 3, 5 and 10% CO2 was added to a constant flow of warm, humidified air through the isolated upper airway. 2. Fifty-three receptors with discharge frequencies modulated by intralaryngeal CO2 were studied. Of these, forty-eight showed CO2-induced attenuation of their firing rates. Pulses of 3, 5 or 10% CO2, alternating with air at intervals ranging from 1.5 to 60 s, also diminished the discharge frequencies. This diminution was greater with higher CO2 concentrations and longer pulse durations. 3. Five of the fifty-three receptors were stimulated by intralaryngeal CO2. The discharge frequencies of these units increased slowly and by only a few impulses per second during CO2 exposure. 4. Thirty-four of the CO2 sensitive receptors were tested with other stimuli, including water, saline, positive and negative intralaryngeal pressures and cold air. The responses to these stimuli varied among receptors, but many of the units that reduced their frequencies with intralaryngeal CO2 were consistently stimulated by positive and/or negative intralaryngeal pressures. 5. Thirty-six of the receptors were anatomically located by probing the upper airway. Twenty-six were in the larynx, and ten were in the rostral trachea, within 5 mm of the cricoid cartilage. 6. The results, which are directly applicable to the investigation of reflex responses reported in the preceding paper, indicate that the predominant initial response to intralaryngeal CO2 under the conditions of these studies is attenuation of laryngeal receptor activity. PMID- 1297834 TI - A role for low-frequency, rhythmic synaptic potentials in the synchronization of cat thalamocortical cells. AB - 1. Low-frequency, rhythmic synaptic potentials and their ability to evoke and modulate membrane potential oscillations in thalamocortical (TC) cells of the cat dorsal lateral geniculate nucleus (dLGN) were investigated using intracellular recordings in a brain slice preparation. Three types of rhythmic synaptic potentials were distinguished: EPSPs, IPSPs and 'complex synaptic potentials' consisting of an IPSP followed by an EPSP. 2. The frequency of all three types of synaptic potentials was insensitive to changes in the membrane potential. At potentials positive to -50 mV, the EPSPs and the complex potentials gave rise to action potentials, while between -65 and -80 mV all three types of synaptic potential evoked low-threshold Ca2+ potentials. TC cells which displayed rhythmic synaptic potentials were either cells that showed spontaneous pacemaker oscillation or cells that were brought to oscillate by the rhythmic EPSPs or depolarizing (i.e. reversed IPSPs. 3. The low-frequency (1.9 +/- 0.2 Hz), rhythmic EPSPs were observed in 23 (out of 192) cells, were abolished by tetrodotoxin (TTX; n = 4) and by the combined application of DL-2-amino-5 phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3), and were insensitive to bicuculline (n = 4). Paired intracellular recordings (n = 32) demonstrated the presence of simultaneously occurring EPSPs in a pair of cells situated 75 microns apart. 4. The low-frequency (2.2 +/- 0.3 Hz), rhythmic IPSPs were observed in 5 (out of 192) cells, were blocked by bicuculline (n = 3), and reversed in polarity at -65 mV. The low-frequency (1.3 +/- 0.3 Hz), rhythmic 'complex potentials' were observed in 5 (out of 192) cells and were abolished by TTX (n = 2). 5. Intracellular depolarizing current pulses delivered at different phases of the pacemaker oscillations revealed the existence of two different types of phase resetting. Furthermore, a current pulse of critical amplitude and duration applied at a specific phase of the cycle abolished the pacemaker oscillations. 6. These results indicate that the low-frequency, rhythmic synaptic potentials recorded in TC cells of the dLGN (i) originate from other TC cells that are in the pacemaker oscillating mode, (ii) are capable of driving other TC cells to oscillate rhythmically, or of modulating the frequency of pacemaker oscillations, and (iii) provide a means by which oscillatory activities of TC cells can be synchronized in the absence of sensory, cortical and reticular thalamic inputs. PMID- 1297835 TI - Histochemical arguments for muscular non-shivering thermogenesis in muscovy ducklings. AB - 1. The histochemical characteristics of gastrocnemius muscle were investigated in 6-week-old cold-acclimated (5 weeks, 4 degrees C) and glucagon-treated (5 weeks, 25 degrees C, 103 nmol/kg I.P. twice daily) muscovy ducklings, two groups able to develop non-shivering thermogenesis in vivo. A comparison was made with thermoneutral controls (25 degrees C) of the same age. All animals were fed ad libitum. Fibre type, fibre area and capillary supply have been studied. Further, a quantitative histochemical method for mitochondrial Mg(2+)-ATPase activity was developed to characterize the mitochondrial coupling state in situ. 2. White gastrocnemius was composed of fast glycolytic (FG) and fast oxidative glycolytic (FOG) fibres, while red gastrocnemius contained FOG and slow oxidative (SO) fibres. In white gastrocnemius, the proportion of FG fibres was higher in glucagon-treated than in control or cold-acclimated ducklings. In red gastrocnemius, the proportion of SO fibres was higher in both cold-acclimated and glucagon-treated ducklings than in controls. The area of all fibres was generally lower in glucagon-treated than in other ducklings. 3. The capillary density was higher in both red and white components of the gastrocnemius muscle in cold acclimated and glucagon-treated than in control ducklings, as a result of an increased number of capillaries around each fibre. 4. In all fibres, except the FG type in cold-acclimated ducklings, the staining intensity of the Mg(2+)-ATPase reaction was higher in cold-acclimated and glucagon-treated than in control ducklings whereas the staining intensity with maximal decoupling of oxidative phosphorylation by dinitrophenol was unchanged. This indicated a more loose coupled state of mitochondria in situ in all fibres of cold-acclimated ducklings, and in FOG fibres of white gastrocnemius and SO fibres of red gastrocnemius in glucagon-treated ducklings. 5. These results indicated a higher oxidative metabolism of skeletal muscle in both cold-acclimated and glucagon-treated than in control ducklings, and for most of the parameters studied, a similarity between cold acclimation and glucagon treatment. Because of the higher loose coupled state of muscle mitochondria in cold-acclimated and glucagon-treated than in control ducklings, the higher oxidative capacity of skeletal muscle in these ducklings could be used for heat production rather than ATP synthesis and account for muscular non-shivering thermogenesis. PMID- 1297836 TI - Respiratory-related activity patterns in preganglionic neurones projecting into the cat cervical sympathetic trunk. AB - 1. Activity in 233 single sympathetic preganglionic neurones that project to the superior cervical ganglion was analysed with respect to central components of respiration (phrenic nerve discharge) and to the afferent feedback generated by mechanical events occurring with ventilation in anaesthetized and artificially ventilated cats. 2. The activity in ninety-one neurones was modulated during the respiratory cycle in two ways: directly by the central inspiratory drive, and indirectly by ventilation-related blood pressure changes, acting via the systemic baroreceptors. The direct influence was prominent in vagotomized animals or those with a raised respiratory drive, and consisted of an inspiratory increase in activity and decreases of activity in early inspiration and postinspiration. The indirect influence (excitation due to baroreceptor unloading) usually dominated in normocapnic cats with intact vagus nerves. This population of neurones showed both similar reflex responses and a similar respiratory modulation of activity as postganglionic neurones supplying hindlimb skeletal muscle. 3. Sixty-one neurones discharged exclusively, or almost exclusively, during central inspiration. This discharge pattern neither depended on the integrity of vagal nor baroreceptor afferents. The activity of these neurones was abolished during hyperventilation and enhanced during hypercapnia. In the latter state, a small activation was often seen in stage II expiration. 4. In normocapnia the remainder of neurones (n = 81) exhibited no, or no pronounced, respiratory modulation of activity, except three neurones which showed a prominent expiratory pattern being of central and not of reflex origin. They were not a homogeneous population and included neurones exhibiting reflex responses similar to those of postganglionic neurones supplying hindlimb skin (n = 36), neurones responding to light (n = 4), and others (n = 41). 5. It is concluded that distinct types of thoracic preganglionic neurone differ with respect to respiratory modulation of their activity stemming from both central and reflex sources. Thus, the temporal profile of activity in these neurones in relation to respiration is another functional characteristic which can be used to distinguish between populations of sympathetic neurones. PMID- 1297837 TI - Characteristic features of noradrenaline-induced Ca2+ mobilization and tension in arterial smooth muscle of the rabbit. AB - 1. Effects of noradrenaline (NAd) on changes in cellular Ca2+ concentration ([Ca2+]i) and tension were investigated, and these effects were compared with those evoked by 128 mM K+ or caffeine in intact smooth muscle strips or by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or caffeine in beta-escin-treated chemically skinned smooth muscle strips of the rabbit mesenteric artery. 2. In physiological solution containing 2.6 mM Ca2+, application of 128 mM K+ or 10 microM NAd produced a phasic, followed by a tonic increase in [Ca2+]i and tension. NAd (10 microM) produced a larger tonic tension than did 128 mM K+ but a smaller increase in [Ca2+]i. When the [Ca2+]i-tension relationship was observed in ionomycin- and 128 mM K(+)-treated muscle strips, 10 microM NAs shifted the relationship to the left and enhanced the maximum amplitude of contraction. These results suggest that NAd increases the sensitivity of contractile proteins to Ca2+ in smooth muscle of the rabbit mesenteric artery. 3. Noradrenaline (10 microM) or caffeine (10 mM), but not 128 mM K+, produced a phasic increase in both [Ca2+]i and tension in Ca(2+)-free solution containing 2 mM EGTA. When 10 mM caffeine had been applied in Ca(2+)-free solution, subsequent application of 10 microM NAd did not increase [Ca2+]i. By contrast, when 10 microM NAd had been applied in Ca(2+)-free solution, subsequent application of 10 mM caffeine still increased [Ca2+]i. Ryanodine (50 microM) abolished the increase in [Ca2+]i induced by 10 mM caffeine or 10 microM NAd in intact and in skinned smooth muscle strips. These results suggest that NAd releases Ca2+ from the ryanodine-sensitive Ca2+ storage sites. 4. Noradrenaline (10 microM) synthesized Ins(1,4,5)P3 in Ca(2+)-free solution in intact smooth muscle strips. Following application of 10 microM NAd, a relatively long time lag (around 1 s) was always observed before the initiation of the increase in [Ca2+]i whether in the presence or absence of Ca2+. The maximum rate of rise of [Ca2+]i induced by 10 mM caffeine was much larger than that induced by 10 microM NAd in Ca(2+)-containing or Ca(2+)-free solution (containing 2 mM EGTA). Both [Ca2+]i and tension reached their peak in a shorter time with caffeine (10 mM) than with 10 microM NAd. In Beta-escin-treated skinned smooth muscle strips, 20 microM Ins(1,4,5)P3 10 mM caffeine or 10 microM NAd increased Ca2+ in Ca(2+)-free solution following brief application of 0.3 microM Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297838 TI - Stellate cell inhibition of Purkinje cells in the turtle cerebellum in vitro. AB - 1. The stellate cell-mediated inhibition of Purkinje cells was studied by intracellular recordings in an in vitro slice preparation of the turtle cerebellar cortex. A graded inhibitory postsynaptic potential (IPSP) was recorded in Purkinje cells upon stimulation of the parallel fibre-stellate cell pathway. 2. The IPSP was abolished by bicuculline, and had a reversal potential around -75 mV, consistent with a GABAA receptor-operated Cl- conductance dominating the response investigated here. 3. Paired recordings from synaptically coupled stellate cells and Purkinje cells demonstrated that the inhibitory input from a single stellate cell is sufficient to reduce the firing in a Purkinje cell. 4. The extracellular-evoked IPSP interacted with the active postsynaptic membrane properties in the Purkinje cell. Interaction with both the Na+ plateau and the IA prolonged the responses to an IPSP, making the net effect of the inhibitory response dependent on the membrane potential in each postsynaptic neurone. 5. A precisely timed IPSP was particularly efficient in reducing dendritic Ca2+ influx. 6. The voltage-dependent Ca2+ component of a climbing fibre response (CFR) as well as of a parallel fibre (PF) input was reduced by the IPSP. 7. It is suggested that Ca2+ spike-mediated reduction in Purkinje cell excitability may be prevented by the stellate cell IPSP-mediated reduction in Ca2+ influx. PMID- 1297839 TI - Studies of transepithelial Cl- transport in cultured cauda epididymal cells of rats by the short-circuit current method. AB - 1. Monolayer cultures of cauda epididymides from male Sprague-Dawley rats (210 230 g) were studied by the short-circuit current (ISC) technique to characterize the properties of the transepithelial chloride transport. In HCO(3-)-free, HEPES buffered solution, adrenaline (0.23 microM) added to the basolateral side led to an increase in ISC and transepithelial conductance (gt). 2. Decreasing apical chloride concentration ([Cl-]a) progressively from 126.7 to 0 mM by substituting chloride with gluconate increased the ISC response to adrenaline (delta ISC) in a linear fashion with a slope of -1.6 x 10(-3) mu equiv h-1 cm-2 per millimolar change in [Cl-]a. Pretreating the tissue with a chloride channel blocker diphenylamine-2-carboxylate (DPC) on the apical side significantly reduced the slope to -4.9 x 10(-4) mu equiv h-1 cm-2 per millimolar change in [Cl-]a. 3. By substituting apical chloride with various anions and measuring the change in ISC upon adrenaline stimulation, the selectivity sequence of the apical anion conductance was found to be NO3- approximately Br- > Cl- > I- > gluconate > isethionate. 4. When the monolayers were bathed with Krebs-Henseleit solution containing 25 mM HCO3- and 5% CO2, the delta ISC at each [Cl-]a as well as the dependence of delta ISC on [Cl-]a (slope = -3.3 x 10(-3) mu equiv h-1 cm-2 per millimolar change in [Cl-]a) were significantly greater than the HCO(3-)-free counterpart. Addition of 0.1 mM acetazolamide or 0.5 mM SITS (4-acetamido-4' isothiocyanatostilbene-2,2'-disulphonic acid) to the basolateral side significantly reduced the effects of HCO3- and CO2. 5. When the tissues were bathed on both sides with HCO(3-)-free, HEPES-buffered solution and were clamped at various transepithelial potential differences (PDt) from +30 mV (lumen positive) to -30 mV (lumen negative), the relationship between the clamping current response to adrenaline (delta ICL) and the PDt applied was linear. Zero clamping current response was found at -6 mV. Decreasing [Cl-]a to 0 mM reduced the dependence of delta ICL on PDt and delta ICL was positive at all PDt tested. The response of the transepithelial conductance to adrenaline (delta gt) did not depend on the PDt applied but was reduced with decreasing apical chloride concentration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297840 TI - Abnormality of superior mesenteric artery blood flow responses in human sympathetic failure. AB - 1. Systemic and regional haemodynamic responses, including superior mesenteric artery blood flow, were measured during stimuli which increase sympatho-neural activity in age-matched normal subjects (controls) and in two groups of patients with sympathetic failure (pure autonomic failure and multiple system atrophy). The stimuli included the pressor tests (mental arithmetic, cutaneous cold and isometric exercise) and head-up tilt. 2. In the controls, the blood pressure did not rise in some during mental arithmetic, but rose in all subjects during cutaneous cold and isometric exercise and was maintained during head-up tilt. In sympathetic failure patients, blood pressure was unchanged during each pressor test and fell during head-up tilt. 3. In the controls, superior mesenteric artery blood flow did not fall significantly during mental arithmetic but fell (with a corresponding rise in calculated superior mesenteric artery vascular resistance), during cutaneous cold, isometric exercise and head-up tilt. In sympathetic failure patients, there were no changes in superior mesenteric artery blood flow and vascular resistance during the pressor tests and head-up tilt. 4. There were no changes in cardiac index or forearm blood flow during each pressor test in both controls and patients. Cardiac index fell and forearm vascular resistance rose during head-up tilt in the controls only. 5. In conclusion, active constriction of the superior mesenteric artery occurs in normal subjects during sympatho-neural activation induced by stimuli such as cutaneous cold, isometric exercise and head-up tilt. This does not occur in patients with sympathetic failure and probably contributes to postural hypotension, emphasizing the role of the splanchnic vascular bed in overall blood pressure control. This study confirms the necessity of integrity of sympathetic pathways in the neural control of the splanchnic vascular bed. PMID- 1297841 TI - Activation of protein kinase C suppresses responses to NMDA in rat CA1 hippocampal neurones. AB - 1. The effects of 1-oleoyl-2-acetylglycerol (OAG), an activator of protein kinase C (PKC), on NMDA receptor-mediated responses were investigated in CA1 neurones of hippocampal slices using current- and voltage-clamp techniques. 2. Topical application of OAG caused a suppression of the slow, voltage-sensitive, NMDA receptor-mediated component of excitatory postsynaptic potentials (EPSPs) evoked by stimulating the schaffer-collateral commissural afferents and had no effect on the fast, voltage-insensitive, quisqualate/kainate component. 3. OAG suppressed the amplitude of inward current responses to NMDA down to about one-third of control responses. OAG could also increase the duration of the responses to NMDA by up to twofold. The effect of OAG on the duration but not on the amplitude of the response to NMDA was blocked by pre-loading cells with the K+ channel blocker, Cs+. Topical application of OAG had no significant effect on current responses to quisqualate. 4. An OAG isomer, which does not activate PKC, had no effect on responses to NMDA. Intracellular application of the kinase inhibitor, H 7, completely blocked the effect of OAG on the amplitude and duration of responses to NMDA, as well as on the slow EPSP. Finally, topical application of another activator of PKC, phorbol 12-myristate 13-acetate (PMA), also suppressed responses to NMDA. PMA reduced the slow component of synaptic responses in about half of the cells tested. 5. We propose that activation of PKC in CA1 hippocampal neurones suppresses NMDA receptor-mediated responses. PMID- 1297842 TI - Detection of slow movements imposed at the elbow during active flexion in man. AB - 1. Subjects' ability to detect movements imposed at the elbow during active flexion was measured. Movements of three different angular velocities (0.04, 0.4 and 4.4 deg/s) were applied to the arm while subjects maintained one of two force levels of active flexion. The threshold magnitudes for detection of the direction of imposed movement were found. 2. All thresholds were very small. At the lowest velocity of movement the average threshold was 0.13 deg and no subject had a threshold of greater than 0.3 deg. This contrasts with thresholds of over 2 deg measured in a previous study when the muscles about the joint were relaxed. Thresholds decreased further with increasing velocity of movement. 3. No difference was found between the two levels of contraction of the elbow flexors. However, extension (stretch of the contracting muscle) and flexion thresholds were calculated separately, and smaller extensions than flexions could be detected. 4. These findings indicate that conscious detection of imposed movements is greatly enhanced during active muscle contraction. Movements which cause unloading of the contracting agonist, as well as movements which result in stretch, are more easily detected than when the muscle is contracting. The discussion focuses on possible mechanisms for this enhancement. PMID- 1297843 TI - The cardiovascular, endocrine and renal response of tetraplegic and paraplegic subjects to dietary sodium restriction. AB - 1. The effects of change from a high to low sodium diet upon renal sodium and water excretion and hormone responses were studied in patients with dissociated sympathetic control (DS, tetraplegic) and controls with sympathetic control largely intact (IS, paraplegic). 2. Total and fractional urinary sodium excretion fell in response to sodium restriction in both groups, but the fall in fractional sodium excretion was greater in the DS group compared with the IS group (DS, 1.34 +/- 0.12 to 0.42 +/- 0.05%; IS, 0.96 +/- 0.08 to 0.52 +/- 0.06%). 3. Supine mean arterial pressure fell during the low salt period in the DS group (80.2 +/- 2.7 to 74.4 +/- 2.3 mmHg) but was unaffected by salt restriction in the IS group (101 +/- 2.3 to 98.8 +/- 2.7 mmHg). In the DS group, creatinine clearance remained constant throughout the low salt period (103.7 +/- 7.9 to 98.3 +/- 9.7 ml min-1), but fell during salt restriction in the IS group (101.4 +/- 8.5 to 83.2 +/- 5 ml min-1). 4. Plasma renin activity was lower during salt loading in DS subjects but increased more rapidly and to higher levels in response to salt restriction (DS, 1021 +/- 142 to 4439 +/- 355; IS, 1765 +/- 269 to 3683 +/- 465 pg angiotensin I ml-1 h-1). Plasma atrial natriuretic peptide concentration was higher in the DS group during salt loading and salt restriction (DS, 37.6 +/- 5.6 to 22 +/- 3.8; IS, 20.2 +/- 2.3 to 11 +/- 1.6 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297844 TI - Differential effects of tetracaine on two kinetic components of calcium release in frog skeletal muscle fibres. AB - 1. Intramembrane charge movements and changes in intracellular calcium concentration were recorded simultaneously in voltage clamped cut skeletal muscle fibres of the frog in the presence and absence of tetracaine. 2. Extracellular application of 20 microM tetracaine reduced the increase in myoplasmic [Ca2+]. The effect on the underlying calcium release flux from the sarcoplasmic reticulum was to suppress the peak of the release while sparing the steady level attained at the end of 100 ms clamp depolarizations. 3. While the peak of the release flux at corresponding voltages was reduced by 62% after the addition of tetracaine, the rate of inactivation was the same when the pulses elicited release fluxes of similar amplitude. 4. Higher concentrations of tetracaine, 0.2 mM, abolished the calcium signal in stretched fibres whereas in slack fibres this concentration left a non-inactivating calcium release flux. 5. Lowering the extracellular pH antagonized the effect of the drug both on charge movements and on calcium signals. The permanently charged analogue tetracaine methobromide lacked effects on excitation-contraction coupling. 6. These results imply that the two kinetic components of calcium release flux have very different tetracaine sensitivities. They are also consistent with an intracellular site of action of the drug at low concentration. Taken together they strongly suggest that the inactivating and non inactivating components of calcium release correspond to different pathways: one that inactivates, is sensitive to tetracaine and is controlled by calcium, and another that does not inactivate, is much less sensitive to tetracaine and is directly controlled by voltage. PMID- 1297845 TI - Dynamics of the ventilatory response in man to step changes of end-tidal carbon dioxide and of hypoxia during exercise. AB - 1. Four human subjects exercised in hypoxia (end-tidal partial pressure of O2 (P(ET),O2) ca 55 Torr; heart rate ca 100-130 beats min-1), and the contribution to the respiratory drive of the peripheral and central chemoreflex pathways have been separated on the basis of the latencies and the time courses of the responses to sudden changes of stimulus. 2. The subjects were exposed to repeated end-tidal step changes in PCO2 of ca 3-3.5 Torr (at nearly constant P(ET),O2) and PO2 (between ca 55 and 230 Torr) at three regions along the expiratory ventilation VE-P(ET),CO2 response line (hypocapnia, eucapnia, hypercapnia). The dynamics of the ventilatory responses were calculated using a two-compartment non linear least-squares optimization method. 3. The component of the response attributable to the peripheral chemoreflex loop may in some subjects contribute up to 75% of the ventilatory drive during mild hypocapnic hypoxic exercise and ca 72% of the total gain following steps of P(ET),CO2 during hypoxic exercise. These data support the notion that the effectiveness of the peripheral chemoreceptor pathway is enhanced in moderate exercise. 4. During hypoxic exercise, the time delays and time constants attributed to the peripheral chemoreflex pathways (ca 3.5 and 9 s respectively) and to the central chemoreflex pathways (ca 9.5 and 47 s respectively) are some of the shortest reported. 5. The dynamics of the peripheral and central chemoreflex pathways appeared to be largely independent of each other. 6. There was a notable absence of systematic change of inspiratory and expiratory durations during the step-induced transients. PMID- 1297846 TI - Control of an external force in leg extensions in humans. AB - 1. We investigated the hypothesis that mono- and bi-articular muscles perform different functions: the former are chiefly dependent on their mechanical advantage, while the latter are considered to be mainly concerned with controlling the direction of an external force. 2. Seven subjects were asked to exert a constant external force in various directions from three different positions. Feedback was given on the amplitude (300 and 600 N) and direction of the force vector. 3. During each trial the position of the subject was registered. Ground reaction force and muscle activity (EMG) from the main mono- and bi-articular upper leg muscles were recorded. Link segment modelling was used to obtain net moments about the knee and hip joints. For each muscle the mechanical advantage was calculated in each force direction. 4. The task of controlling the ground reaction force was performed with little interindividual variation as reflected by the variability of the different force and EMG variables. 5. A linear relationship between the difference in activity of rectus femoris and hamstrings and the difference in net moment around the knee and hip was found. This relationship showed very high correlation coefficients of 0.96 (300 N) and 0.97 (600 N) and was independent of position. Mean correlations between this activity difference and the angle of the force vector were also high: -0.95 (300 N) and -0.94 (600 N). 6. The mono- as well as the bi-articular muscles increased in activity when a larger mechanical advantage could be obtained from them, except for the biceps femoris (short head). 7. The results support the hypothesis that bi-articular muscles have a unique role in controlling the distribution of net moments about the joints, and as a consequence, in controlling the direction of the external force exerted on the environment. PMID- 1297847 TI - Myofibrillar fatigue versus failure of activation during repetitive stimulation of frog muscle fibres. AB - 1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria (temperature, 2-5 degrees C; sarcomere length, 2.10 microns) were fatigued using two separate protocols that led to different degrees of depression of tetanic force. Under control conditions the fibre was stimulated to produce a 1 s fused isometric tetanus at 300 s intervals. A moderate degree of fatigue (tetanic force reduced to 70-80% of the control value) was produced by decreasing the intervals between tetani to 15 s ('fatiguing protocol 1'). A more pronounced depression of tetanic force (to 40-50% of the control value) was produced by evoking a single twitch at 1-2 s intervals ('fatiguing protocol 2'). 2. Fatiguing protocol 1 reduced the contracture response to submaximal and supramaximal concentrations of caffeine (3-15 mM) in proportion to the decrease in tetanic force. These results support the view that fatiguing stimulation according to protocol 1 leads to a true 'myofibrillar fatigue' with no failure of activation of the muscle fibre. 3. Fatiguing protocol 2 reduced the amplitudes of isometric twitch and tetanus to below 10 and 50% of the control values, respectively. By contrast, the maximal contracture response to caffeine (15 mM) was depressed by merely 2-3% of its prefatigue value. 4. Force and instantaneous fibre stiffness were recorded simultaneously during twitch and tetanus as fatigue was induced by protocol 2. During the initial part of fatigue (tetanic force reduced by 25% of control) stiffness was reduced by merely 9% in accordance with previous measurements during fatigue induced by protocol 1. However, with further depression of twitch and tetanus by protocol 2 there was a marked reduction of fibre stiffness. These results, together with the findings reported under point 3, strongly suggest that at an advanced state of fatigue induced by protocol 2 the decrease in active force is largely due to failure of activation of the contractile system. 5. Muscle fibres were quickly frozen for electron microscopical examination after shortening below slack length (to approximately 1.6 microns sarcomere spacing) during tetanic stimulation. In non-fatigued fibres, and in fibres fatigued according to protocol 1, the myofibrils exhibited a straight appearance throughout the preparation suggesting that the entire volume of the fibre was properly activated. In fibres fatigued by protocol 2, on the other hand, only the most peripheral layers of myofibrils remained straight after shortening, whereas the centre of the fibre showed marked waviness indicating failure of the inward spread of activation in this case. PMID- 1297849 TI - The effects of ventricular end-diastolic and systolic pressures on action potential and duration in anaesthetized dogs. AB - 1. Although it is known that mechanical events in the heart influence the duration of the cardiac action potential, there is no quantitative information on the effects of independent changes in ventricular end-diastolic and systolic pressures. 2. Experiments were carried out on open-chest anaesthetized dogs in which the autonomic nervous influences on the heart were prevented and monophasic action potentials were recorded form the epicardial surface of the left ventricle. The duration of these action potentials was taken as the interval from the upstroke to the point of 90% repolarization. 3. Elevation of left ventricular peak systolic pressure, at constant end-diastolic pressure, significantly shortened the monophasic action potential. 4. Elevation of end-diastolic pressure at constant peak systolic pressure significantly lengthened the monophasic action potential. 5. Responses were not dependent on release of noradrenaline from sympathetic nerve terminals because they persisted after administration of bretylium tosylate. They were also not due to myocardial ischaemia because they persisted when coronary perfusion pressure was maintained at a constant high level. 6. Simultaneous recordings of changes in myocardial segment length showed the expected responses to changes in ventricular pressures: increases in shortening in response to increases in diastolic pressure and no consistent effect from changes in systolic pressure. 7. These investigations demonstrate the independent effects of changes in systolic and end-diastolic pressures on cardiac action potential duration. This effect is likely to be an effect of the mechanical events, i.e. contraction-excitation feedback. This response may be mediated through changes in myocardial fibre tension, the consequent changes in fibre shortening, or both. PMID- 1297848 TI - Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea-pig hippocampus. AB - 1. Intracellular recordings, taken from CA1 pyramidal cells in guinea-pig hippocampal slices, were used to examine the origins of repetitive and burst firing in these cells. Single action potentials were elicited by depolarizing current injection at somatic recording sites. In contrast, current injection during intradendritic recordings initiated burst firing in the dendrites. Burst firing could be elicited in the soma by direct depolarization of distal apical dendrites (> 150 microns from the cell body layer) with large extracellular polarizing electrodes. 2. Intracellular recordings were taken simultaneously from the apical dendrites and pyramidal cell somata with the intention of impaling the same neurone with both electrodes. Paired dendrite-soma recordings confirmed that rhythmic single action potentials were generated at the cell soma, whereas bursts of action potentials were initiated in the distal apical dendrites (> 150 microns from the cell body layer). Fast spikes in the dendrite often triggered fast spikes in the soma, but not all fast spikes in the dendritic burst were 'relayed' to the soma. 3. In paired recordings, when a dendritic action potential failed to elicit a full somatic action potential, a 'd-spike' was commonly recorded in the soma. Somatic d-spikes were uniform all-or-none responses that could be shown, in some cases, to trigger the full somatic action potentials. 4. Attenuated spikes could be recorded in the dendrites, triggered by action potentials initiated at the cell soma. Dendritic responses to somatic stimulation sometimes varied in amplitude, but always showed a direct correspondence with somatic action potentials. 5. Dendritic recordings taken closer to the pyramidal cell bodies (< 150 microns from the cell body layer) showed a 'transitional' region where single action potentials rather than burst discharges could be evoked. After-potentials of these single spikes differed from those associated with somatic spikes in that proximal dendritic spikes had depolarizing after-potentials. The observed shift from after-hyperpolarization to depolarizing after-potentials in intradendritic recordings taken progressively further from the cell body corresponds to the change from repetitive to burst firing. 6. The results indicate that activity of the CA1 pyramidal cell soma, presumably a reflection of its output, can be either burst or repetitive firing. Somatic 'bursts,' unlike the burst discharges seen in the apical dendrites or the burst discharges reported in CA3 cells, are not initiated locally. Rather, they appear to be simply a rapid spike-for-spike response by the soma to the fast spikes that form part of the apical dendritic burst.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1297850 TI - Developmental biology of the common marmoset: proposal for a "postnatal staging". AB - The published knowledge on neurobiological, psychological, and ethological aspects of development in Callithrix jacchus is still limited. We have collected published and unpublished data from several Callithrix colonies and pooled information on criteria for developmental progress and maturation using a questionnaire sent to numerous experts in the field. The data suggest that developmental stages can be defined not only for the embryonic and fetal but also for the postnatal period. Based on multifactorial definitions, using criteria selected from maturational changes in the motor and visual systems and behavioral features, we propose to subdivide postnatal development of the common marmoset into seven periods ("stages"). PMID- 1297851 TI - Transmission of SIVMne from female to male Macaca nemestrina. AB - Three SIVMne-infected female pigtailed macaques (Macaca nemestrina) were mated with two SIV-negative males. The females exhibited signs of SAIDS and SIVMne was readily isolated from peripheral blood mononuclear cells (PBMC). Both males became infected with SIVMne, developed SAIDS, and died. This is the first documented case of the transmission of SIVMne between adult macaques housed together. Although transmission through scratching or biting cannot be ruled out, heterosexual transmission appears the most likely mode of SIVMne transmission in this study. PMID- 1297852 TI - Sonographic assessment of nongravid female macaques (Macaca mulatta and Macaca fascicularis). PMID- 1297853 TI - Cyclic changes in the charge profile of LH in anterior pituitary glands of adult female Japanese monkeys (Macaca fuscata). PMID- 1297854 TI - Measurement of serum IgE antibodies against Japanese cedar pollen (Cryptomeria japonica) in Japanese monkeys (Macaca fuscata) with pollinosis. AB - IgE antibodies against allergens of Japanese cedar (Cryptomeria japonica, CJ) pollen in the serum of seven Japanese monkeys (Macaca fuscata) with pollinosis were measured by fluorometric indirect enzyme-linked immunosorbent assay (ELISA). All of the monkeys were found to have specific IgE to the crude pollen antigen. The specific IgE levels were well correlated with those determined by the Pharmacia CAP system. IgE antibodies were then assayed with two kinds of purified allergens (Cry j I and Cry j II) by the ELISA. We found that five monkeys had specific IgE to both allergens, although the other two had IgE only to Cry j I or Cry j II; there is different immune responsiveness to the two major allergens in the monkeys. PMID- 1297855 TI - Dependence of biphasic heart rate response to sustained hypoxia on magnitude of ventilation in man. AB - We studied the dynamic profile of respiratory and circulatory activities during sustained isocapnic hypoxia in healthy males. In response to end-tidal PO2 depression to about 55 Torr, minute ventilation first increased briskly and then depressed. Such biphasic response to hypoxia was also observed in the heart rate. A significantly positive correlation was found between the magnitudes of ventilatory and heart rate responses. No significant increases were found in arterial noradrenaline and potassium, but adrenaline significantly increased gradually with time. Furthermore, when VT and f were intentionally maintained constant so as to prevent the biphasic ventilatory change, the biphasic heart rate response previously seen in spontaneous hypoxic breathing disappeared. We suggest that the heart rate is mainly determined by the pulmonary vagal inflation reflex. Putative neurochemicals to elicit hypoxic ventilatory depression, and arterial catecholamine and potassium concentrations may not be directly related to the specific profile of the biphasic heart rate response during moderate hypoxia. PMID- 1297856 TI - Peripheral vascular response to local cold stress of tropical men during sojourn in the Arctic cold region. AB - Peripheral vascular response to local cold stress was studied on 4 groups of volunteers by eliciting cold-induced vasodilatation (CIVD) response during immersion of right hand in cold water (4 degrees C) for 30 min, to examine whether tropical men can get acclimatized to local cold compared to temperate zone people, during Arctic cold exposure. Group A and B (10 each) were drawn from tropical region of India, while Group C and D (6 each) from temperate zone of Russia and natives of Arctic, respectively. Initial study was conducted on control Group A at Delhi. Group B was airlifted to the Arctic (70 degrees N, 38 degrees E), where measurements were done on them during the seventh week of acclimatization, then they were flown back to Delhi and retested. For comparison, study was done at the Arctic on six migrants (Group C) from temperate zone of Russia and 6 natives (Group D) of the Arctic. There was a significant improvement of CIVD response and peripheral blood flow of tropical men due to acclimatization to Arctic environment, which was similar to that of the migrants but lower than the natives. Thus local cold acclimatization is possible even in tropical men as in those of the temperate zone people. PMID- 1297857 TI - Possible role of red cell deformability and microvasculature in microcirculation. AB - The roles of the deformability of red blood cells (RBC) and the microvasculature in the maintenance of blood flow were investigated in terms of the pressure (P) flow rate (Q) relationships in human RBC suspension perfusions of bullfrog hind limb. Although isotonicity for the bullfrog is approximately 215 mOsm/kgH2O, perfusions in intact hind limbs showed no change in the P-Q relationship at test solution osmolalities ranging from approximately 150 to approximately 300 mOsm/kgH2O. The deformability of RBC was examined in glutaraldehyde-fixed hind limbs. Perfusion of fixed limbs with RBC suspension revealed minimum resistance to flow at osmolalities of approximately 250 to approximately 420 mOsm/kgH2O, whereas the same experiment in intact limbs revealed minimum flow resistance at osmolalities of approximately 200 to approximately 300 mOsm/kgH2O. It was noteworthy that the reduction of RBC deformability was not observed in intact limbs at osmolalities of approximately 250 to approximately 200 mOsm/kgH2O. Heinz body-forming RBC from a patient with unstable hemoglobin (Hb) disease (Hb Yokohama) exhibited a marked reduction in deformability as compared with normal RBC in fixed limbs, while there was no discernible difference between the two types of RBC in intact limbs, thereby suggesting that the microvascular bed can compensate, to an appreciable extent, for the impaired deformability of RBC, probably via its distensibility and/or a wall effect. The present study has considerable implications concerning the link between in vitro experiments and the in vivo situation, including the hemodynamic characteristics of RBC suspensions such as the effective viscosity. PMID- 1297858 TI - Expiratory activity of the inspiratory muscles during cough. AB - To investigate the neural mechanism of the expiratory activity of the inspiratory muscles during a cough, EMG of the respiratory muscles were recorded in anesthetized and tracheostomized dogs. A laparoscope was used to minimize injury to the abdominal muscles for implantation of the electrodes into the costal diaphragm. During the expulsive phase of a cough, the diaphragm was active in 7 of 12 dogs and the external intercostal muscle was active in 3 of 6 dogs. During a cough, the expiratory activity of the diaphragm, after the termination of its inspiratory activity, started at 52.9 +/- 24.6 ms, and that of external intercostal muscle started at 51.1 +/- 20.5 ms. The expiratory activity of the internal intercostal muscle and of the transversus abdominis started at 34.3 +/- 13.0 and 27.8 +/- 15.2 ms, respectively. The onset of expiratory activity of the inspiratory muscles is significantly later than that of expiratory muscles. Continuous activity in the expiratory muscles evoked by airway occlusion, i.e., Hering-Breuer reflex, was suppressed during the inspiratory phase of a cough, but not suppressed during the expulsive phase even when the expiratory activity of the diaphragm was observed. We concluded that the expiratory activity of inspiratory muscles is controlled independently of both expiratory activity of the expiratory muscles and inspiratory activity of the inspiratory muscles. PMID- 1297859 TI - An analysis of post-contracture potentiation in frog twitch skeletal muscle. AB - Post-tetanic potentiation (PTP) was mimicked by post-contracture potentiation (PCP) in the twitch muscle of frog. A marked PCP was observed in small bundles of semitendinosus muscle in tetrodotoxin (TTX)-containing solution under current clamp condition. Contractures were induced by a constant depolarizing current pulse of 1 s every 5 min. Each contracture (C) was preceded and followed by a twitch-corresponding short contracture, T1 and T2, with an interval of 2 s. The ratio of twitch height, T2/T1, was measured and compared under various conditions. In TTX-containing Ringer solution, T2/T1 depended on magnitude of both T and C. When T2/T1 was plotted against C/T1 a quasi-linear relationship was found. The slope of the curve was 0.076 and was found to decrease when the duration of T was increased to 1 s. In TTX-containing solution, addition of 2 mM Ba2+ or 1 mM caffeine potentiated T as well as C but decreased T2/T1 markedly. Similar effects were observed when Na+ was replaced with TEA+ or when bath temperature was lowered from 20 to 8 degrees C. In all cases T2/T1 vs. C/T1 curve was shifted to the left and downwards. It was considered that these results could be attributable to an elevation of the resting Ca2+ concentration in the sarcoplasm. Thus the phenomenon of PCP probably reflects the time course of Ca2+ transients in the conditioning contracture C. PMID- 1297860 TI - Effects of time-varying electromagnetic fields on K+ (Rb+) fluxes and surface charge of HeLa cells. AB - The magnetic flux density was varied intermittently from 0.35 to 1.77T and from 0.07 to 1.54 or 1.77T by manual and automatic switchings, respectively, of the power source of an electromagnet. The durations of the "switching-on time" and " off time" were varied but kept equal. An electric eddy current induced in the culture medium by changes in the magnetic flux density was simulated. When the durations were shorter than 10s, ouabain-sensitive Rb+ influx (active K+ influx) into cultured HeLa cells was significantly inhibited, but the ouabain-insensitive Rb+ influx (passive K+ influx) was not influenced significantly. Inhibition of active Rb+ influx increased with time during exposure for 2 h. Conversely, K+ efflux from the cells was significantly stimulated by the exposure. Microfluorometric examinations of cells loaded with the fluorescent pH indicator 4-heptadecyl-7-hydroxycoumarin (6 microM) and the membrane potential indicator diS-C3-(5) (1 microM) suggested increase in the negative charge on the cell surface during exposure. The observed changes in the K+ (Rb+) fluxes would be related to change in the electric properties of the cell surface caused by exposure to intermittent electromagnetic fields. PMID- 1297861 TI - Effects of mechanical stretch on membrane currents of single ventricular myocytes of guinea-pig heart. AB - A technique to record whole cell membrane current during stretching single cardiac myocytes was developed. Ventricular myocytes were dissociated by treating guinea-pig hearts with collagenase. One end of the cell was fixed either to a microglasstool tip or to a glass plate, while the other end was attached either to a microglasstool tip or to a suction pipette, which was mounted on a micromanipulator. A time-independent current showing a reversal potential of -15 +/- 4 mV (n = 7) was activated when the myocytes were stretched more than 20% of the length between two fixed point. The current gradually relaxed during the maintained stretch, and disappeared on releasing the stretch. We failed to detect any consistent change in either the L-type Ca2+ current or the inward rectifier K+ current. For comparison, current changes induced by inflating the cell using a hypo-osmotic solution were recorded. The inflation was not accompanied by any change in the time-independent current. Instead, the delayed rectifier K+ current was increased to 170 +/- 48% control by the 70% hypo-osmotic solution. Thus, the effect of mechanical stretch on the time-independent current is different from those of hypo-osmotic cell inflation. The stretch-induced time-independent current is compared with reported current changes induced by the intracellular microinjection of Ca2+. PMID- 1297862 TI - The effects of leg-cooling on blood lactate disappearance following supramaximal exercise. AB - In order to clarify whether leg-cooling after supramaximal treadmill exercise will change lactate disappearance rate from venous blood, blood lactate, calf blood flow, and skin temperature were determined in cold application and non-cold application recovery. In the cooling experiments, both legs were cooled with ice packs for 23 min during recovery. The skin temperature was significantly lower in the cold application as compared with the non-cold application. However, no significant difference was found in the blood lactate and/or calf blood flow between cold and non-cold conditions. In addition, there was no significant difference in the slope of regression line (blood lactate/blood flow) between cold and non-cold applications. These results suggest that no significant difference in the blood lactate between cold and non-cold applications could be explained by the lack of difference in the blood flow between cold and non-cold applications. PMID- 1297863 TI - Osmotically inactive space during hyperosmotic stress in the perfused submandibular gland of the rat. AB - Cell volume changes were measured by an impedance method during hyperosmotic stress in the perfused rat submandibular gland. When the perfusate osmolarity was raised to 484 mosmol, the cell volume decreased and remained at a plateau level (79%). The decrease was smaller than expected from the extracellular fluid osmolarity change. Furthermore, the potassium content of the gland increased by 7% during the hyperosmotic stress. These results suggest that the cell volume changes observed during hyperosmotic stress are affected by the existence of an osmotically inactive space and by an increase in the intracellular solute content. PMID- 1297864 TI - Stretch-induced force development in Mytilus smooth muscle during submaximal activation. AB - When the anterior byssal retractor muscle of Mytilus edulis is stretched by 5-20% during submaximal activation with 100 mM K+ or 10(-5) M acetylcholine, it exhibited a delayed force development after the completion of stretch. The effect of ions and drugs on the stretch-induced activation suggests the stretch-induced release of Ca2+ from the inner surface of the plasma membrane. PMID- 1297865 TI - An improved method for measurement of sweat expulsions during profuse sweating. AB - We present an improved ventilated-capsule method of recording for clear sweat expulsion patterns using nitrogen gas as a carrier gas heated to promote sweat evaporation. With this method, sweat expulsion patterns were more clearly recorded than with the conventional ventilated-capsule method. Taking the derivatives of these recordings of sweating expulsions could eliminate slow fluctuation components in the patterns of sweating. The results indicate that this method is useful in providing more-accurate measurements of sweat expulsion frequencies during profuse sweating. PMID- 1297866 TI - [Function of the serotoninergic system of blood platelets in patients with hypertension]. AB - To investigate if there can be alterations in the 5-hydroxytryptamine (5-HT) uptake system in the sensitivity of platelets in patients with essential hypertension, 38 hypertensive patients and 37 normotensive healthy subjects were compared. In patients, the maximal 5-HT uptake velocity was reduced. The density of binding sites for 3H-imipramine was elevated in hypertensive females, but unchanged in males. The sensitivity of 5-HT uptake to trazodone was unchanged in patients. Half-maximal concentrations of 5-HT for inducing a shape change reaction of platelets were positively correlated with diastolic blood pressure in male patients and were reduced in female mild hypertensives. It is suggested that these changes are likely to be involved in the pathogenesis of hypertension. PMID- 1297867 TI - [Surgical treatment of patients with atherosclerotic lesions of blood vessels of the heart, brain, and lower extremities]. PMID- 1297868 TI - [Expedience of using the term "mild hypertension" in clinical practice]. PMID- 1297869 TI - [Emergencies in dilated cardiomyopathy and myocarditis]. PMID- 1297870 TI - [Comparative hypotensive effectiveness of various calcium antagonists in patients with persistent essential hypertension (randomized study)]. PMID- 1297871 TI - [Baroreflex control and circadian variability of arterial blood pressure in patients with "mild" hypertension and hemodynamically insignificant atherosclerotic lesions of the carotid arteries]. AB - Sinocarotid baroreflex control by means of the neck chamber technique (-40 mm Hg, 4 min) and blood pressure monitoring with a SpaceLabs 90207 system were performed in 45 patients with mild essential hypertension who were divided into 2 groups: (1) those with hemodynamically insignificant carotid atherosclerotic lesions (n = 19) and (2) those without them (n = 26). Group 1 patients showed a decreased cardiochronotropic component of baroreflex control, higher blood pressure variability and less pronounced nocturnal blood pressure fall. The above facts are likely to contribute to progression of essential hypertension and aggravation of target organ lesions. PMID- 1297872 TI - [Testing of arterial hypertension with physical exercise PWCx ]. AB - The relation of physical fitness (PF) to blood pressure (BP) and arterial hypertension risk factors was studied in a representative sample by PWCX exercise testing. The relations were studied at the initial stage, during exercise and recovery by using the multivariance stepwise regression analysis. This complex approach allowed the independent relation of PF to BP to be found. In normotensive males, systolic BP determined 4% PF variability after the first exercise, while in hypertensive males, the second exercise heart rate and age determined 27 and 9% PF variability, respectively. In normotensive females, the first exercise heart rate determined 62% PF variability, in hypertensive females, the second exercise systolic BP and age determined 4 and 2% PF variability, respectively. The value x shows the relation of PF to heart rate and BP in the restorative period and is an additional significant parameter of PF and the functional status of the cardiovascular system. PMID- 1297873 TI - [Application of biomechanical stimulation of lower extremity muscles in the treatment of patients with hypertension]. AB - The impact of biomechanical stimulation of lower extremity muscles was studied in patients with essential hypertension on systemic blood pressure and its hemodynamic components. A short-term (10-15-minute) antihypertensive effect was found in a 2-minute stimulation session. Inclusion of biomechanical stimulation into the multimodality treatment of patients with Stage II hypertensive disease will enhance its efficiency. The mechanism responsible for the depressive effects of biomechanical stimulation and the role of the hemodynamic pump function of skeletal muscles in this process are discussed in the paper. PMID- 1297874 TI - [Transesophageal electrostimulation of the atrium in patients with ischemic heart disease combined with arterial hypertension in disability evaluation ]. AB - The author studied 78 patients (60 males and 18 females) aged 36 to 60 years (mean age 50 +/- 6 years). They all were diagnosed as having coronary heart disease (CHD) concurrent with arterial hypertension. Transesophageal atrial pacing test (TEACT) was positive in 68 (87.2%), and negative in 4 (5.1%) patients. It failed to reach diagnostic ECG criteria in 6 (7.7%) patients. A close relationship was found between the number of diseased coronary arteries and the sensitivity of TEACT. The TEACT parameters were found to be related to bicycle ergometric ones. The findings showed that the threshold rate of induced rhythm decreased when the patients increased their functional class of exercise induced angina pectoris, the appearance of ST-segment depression being delayed and its disappearance increased. Thus, transesophageal atrial pacing allows the functional class to be defined in patients with CHD concurrent with arterial hypertension from the threshold rate of imposed rhythm and the time of ST-segment depression appearance and disappearance and can be useful both in the diagnosis and appraisal of the working capacity in patients with coronary heart disease concurrent with arterial hypertension. PMID- 1297875 TI - [Endovascular prosthesis of a coronary artery in acute myocardial infarction]. PMID- 1297876 TI - [Antianginal activity of cardil and cordafen in patients with non-Q wave myocardial infarction]. AB - The antianginal activity of Cardil, 240-360 mg/day, and Cordafen, 30-60 mg/day, was evaluated in 74 patients with non-Q wave acute myocardial infarction. Repeated 24-hour ECG monitoring was used as an objective tool for the evaluation of their therapeutical efficiency in two randomized groups. Unlike Cordafen, Cardil significantly reduced the average heart rate from 4.7 to 1.5 and the average duration from 20.5 to 11.5 min and the average total duration of myocardial ischemic episodes from 95.1 min/day to 16.7 min/day. Both Cardil and Cordafen considerably reduced the total duration of painful ischemic attacks, but only did Cardil reduce silent episodes (p < 0.001). Both Cardil and Cordafen substantially reduced resting ischemia, but Cardil also decreased the rate of exercise-induced ischemic episodes (p < 0.05). PMID- 1297878 TI - [Possibilities for the rehabilitation of patients with myocardial infarction without application of coronary drugs during hospital treatment ]. AB - When restorative treatment was performed in 51 patients with myocardial infarction, 3 groups were identified, each including 17 persons. The main group comprised those whose rehabilitation had been achieved by early physical trainings with coronary active agents; the first control consisted of those who had gone in for physical exercises and received antianginal drugs, the second control group included those whose rehabilitation had been conducted by the well known procedures (therapeutical exercises, graded walking, nitrates, beta blockers, calcium antagonists). The treatment resulted in improvement in the functional status of patients from the main and the first control groups as compared to those from the second control group. It is concluded that in patients with myocardial infarction without pain syndrome in the subacute period of the disease the efficiency of restorative treatment may be enhanced by using early individualized physical trainings without application of coronary active drugs. PMID- 1297877 TI - [Impact of exercise test on signal-averaged ECG in patients with myocardial infarction]. AB - To examine the impact of exercise test (bicycle ergometry) and exercise-induced transient ischemic changes in ST segment on signal-averaged ECG parameters, the authors studied a homogeneous group including 65 patients (62 males and 3 females) with a 2-3-week history of primary myocardial infarction. The findings showed that induced myocardial ischemia caused no significant changes in signal averaged ECG and late potentials, exercise might induce late potentials without clear-cut ECG signs of myocardial ischemia. It was also indicated that exercise labile late potentials were significantly more frequently associated with the development of ventricular arrhythmias than steady late potentials. PMID- 1297879 TI - [X syndrome: does left ventricular myocardial perfusion suffer during exercise?]. AB - Sixteen patients with the X syndrome underwent thallium-201 myocardial scintigraphy. Eleven patients with one-coronary artery disease served as a control group. During bicycle ergometry all the 16 patients showed various degrees of local myocardial perfusion impairments. The foci were located in the basins of various coronary vessels. Impaired myocardial perfusion in patients with the X syndrome was similar to that in patients with moderate, but hemodynamically significant stenosis of a coronary artery. At the same time the impairments were significantly less pronounced than in those with critical stenosis of a coronary artery. Thus, patients with the X syndrome have not only clinical signs of coronary heart disease (anginal episodes), but they also have marked myocardial perfusion impairments during exercise. PMID- 1297880 TI - [Responses of peripheral blood circulation in treadmill exercise test as a criterium for evaluation of central hemodynamics and anaerobic threshold]. AB - The study was undertaken to examine whether the linear arterial blood velocity in the lower extremities is related to impaired cardiac pump function and anaerobic threshold. A stepwise treadmill test was performed in 40 healthy individuals and 39 patients with cardiac malformations. The changes in maximal diastolic blood velocity and resistive index which had been determined by Doppler echoflowmetry after each step of the treadmill test were compared with those in the oxygen restoration coefficient, ventilation equivalent by oxygen and carbon dioxide levels in the expired air. It was found that the blood velocity in the lower extremities may be used as noninvasive criteria for impaired cardiac pump function and anaerobic threshold. PMID- 1297881 TI - [Role of serotonin and its receptors in the pathogenesis of arterial hypertension]. PMID- 1297882 TI - [Use of immunosorption for selective decrease of lipoprotein (A) levels in patients with coronary atherosclerosis]. AB - Lipoprotein (a) [L(a)] is an atherogenic lipoprotein, its human plasma concentration correlates with the occurrence of coronary heart disease. The procedure for selectively removing L(a) with an anti-L(a) immunosorbent was performed to treat 3 patients who had high L(a), normal total cholesterol and other lipoprotein levels. All the patients had coronary stenosis as documented by angiography. After L(a)-apheresis, the level of L(a) decreased by 72%, while that of other plasma components, including low density lipoproteins virtually unchanged. Thus, the procedure of L(a)-apheresis is an effective and safe method for lowering human blood L(a) concentrations. In addition, this in vivo model allows information on L(a) metabolism to be obtained. PMID- 1297883 TI - [Dietary treatment of patients with familial hyperlipoproteinemias]. PMID- 1297885 TI - [Effect of activated leukocytes on platelet aggregation in patients with ischemic heart disease]. PMID- 1297884 TI - [Impact of exercise on alimentary hyperlipoproteinemia in patients with ischemic heart disease]. AB - The impact of graded exercises of various intensity and duration on serum lipoprotein values was examined in 20 patients with coronary heart disease (CHD) and 10 healthy individuals after a single dietary fat load (FL). FL resulted in hypertriglyceridemia which was accompanied by elevated apo-AI levels and reduced apo-B/apo-AI ratio in the healthy persons, whereas it was accompanied by lower apo-AI levels and increased apo-B/apo-AI ratio in the patients. The short-term maximum exercise in the presence of FL caused negative shifts in the lipid transport system both in the healthy persons and the patients, by elevating the level of apo-B-containing lipoproteins. Yet, the healthy individuals showed a further increase in apo-AI concentrations. The long-term exercise in the training mode corrected changes in lipid values, which had been induced by FL in the two groups of the examinees. There was a decrease in the levels of triglycerides, low density lipoprotein, cholesterol and an increase in the level of high density lipoprotein cholesterol. PMID- 1297886 TI - [Correlation of antianginal effect of corinfar and diastolic function in patients with ischemic heart disease]. AB - The study was undertaken to examine 45 patients with coronary heart disease and 14 healthy subjects by using radionuclide ventriculography, apex- and echocardiographies, bicycle ergometry, transesophageal electrocardiostimulation before therapy and at the action peak of corinfar in a dose of 30 mg. It was shown that corinfar failed to affect the unaltered diastolic function of the left ventricle. The normalizing effect of corinfar on left ventricular stiffness was found to result in higher coronary reserve, significantly enhanced exercise tolerance and to be an important mechanism of antianginal effect of the drug. Impaired left ventricular stiffness may be an additional criterion for using corinfar in patients with coronary heart disease. PMID- 1297887 TI - [Effect of various antianginal agents on the frequency and duration of myocardial ischemic episodes in patients with stable angina pectoris]. AB - The effects of verapamil, nifedipine, propranolol, and combinations of nifedipine+propranolol and nifedipine+verapamil were studied in 60 patients with stable angina pectoris. Verapamil was found to have a pronounced antianginal activity against all types of myocardial ischemia, whereas nifedipine relieved mainly painful ischemic episodes. By the end of 12-week therapy with propranolol, the agent lost its antiischemic effect in a third of patients, which was accompanied by an increase in the number and severity of silent ischemic episodes. PMID- 1297888 TI - [ Combined therapy with isosorbide dinitrate, propranolol and nifedipine in patients with chronic ischemic heart disease]. AB - Forty six patients with stable effort angina were treated with a combination of propranolol, nifedipine, and isosorbide dinitrate which produced a more profound anti-antianginal effect than each of them given alone. The combination also exerted more marked antihypertensive and antiarrhythmic effects. The combined therapy with the three drugs caused a moderate reduction in heart rate and peripheral resistance, but failed to result in clear-cut disturbances in the orthostatic regulation of the circulatory system. There was a more infrequent and less pronounced ST-segment depression, less marked pressor responses and higher heart rate with the combined therapy during exercise; the cardiac index also increased as before therapy. Physical fitness increased to a greater extent than with monotherapy. The combined therapy with three drugs is indicated when monotherapy fails and that with two agents is indicated when patients have concurrent essential hypertension and cardiac arrhythmias. PMID- 1297890 TI - [Reversal of withdrawal injuries of the heart and liver by adaptation to intermittent hypoxia when discontinuing ethanol in chronically alcoholized animals]. AB - Adaptation to intermittent hypoxia in the hypobaric altitude chamber showed a two fold decrease in ethanol consumption in chronically alcoholized rats and attenuated or arrested the withdrawal syndrome. The impact of adaptation to the withdrawal syndrome was that it prevented the development of withdrawal analgesia, higher alcohol consumption after its withdrawal, withdrawal hepatic activation of lipid oxidation products and blood release of the hepatic specific enzymes fructose monophosphataldolase and gamma-glutamyl transpeptidase. Concurrently, the adaptation prevented the withdrawal fall of the cardiac fibrillation threshold and marked disorders of ventricular contraction and relaxation. The paper discusses whether adaptation to intermittent hypoxia can be used in the management of the types of alcoholism in whose development the withdrawal plays the key role. PMID- 1297889 TI - [Comprehensive evaluation of the severity of illness in patients with ventricular arrhythmias by using a mathematical method]. AB - A comprehensive method for objectivization of the condition in patients with ventricular arrhythmias has been first developed and tested. Equations for determining the severity indices for ventricular arrhythmias, coronary dysfunction, heart failure, and arterial hypertension have been derived on the basis of isolation and mathematical formalization of clinical and instrumental signs of the above abnormalities. With the derived indices it is possible to make a valid comprehensive assessment of the severity of ventricular arrhythmias, to identify the syndrome predominant in the clinical course of the syndrome, and to quantify the efficiency of inpatient and long-term outpatient therapy. PMID- 1297891 TI - Effect of amphotericin B alone or in combination with rifampicin on phagocytosis of Candida species by human polymorphonuclear leukocytes. AB - The influence of amphotericin B and rifampicin alone and in combination on the killing of Candida albicans, Candida tropicalis and Cryptococcus neoformans by human polymorphonuclear leukocytes was investigated in vitro. Granulocytes were harvested from the blood of healthy volunteers and resuspended with the above mentioned fungi. After 6 hours, 81.5% of C. albicans, 97% of C. tropicalis but only 34% of C. neoformans were killed. The activity of amphotericin B against C. albicans and C. tropicalis was better in granulocyte-free medium. A synergism between amphotericin B and rifampicin towards Candida could be detected. It was also demonstrated in the presence of polymorphonuclear leukocytes with a factor > 1 log in reduction of colony count. However, whether granulocytes were present or not, rifampicin (4 mcg/mL) alone did not exert any influence on growth of Candida. PMID- 1297892 TI - Radiolabelled calmodulin ligands: their low affinity and high lipophilicity may lead to artefacts in binding studies. AB - In order to characterize the interaction site of a series of putative calmodulin antagonists of the diphenylalkylamine type with calmodulin (CaM), a representative member of this chemical class was radiolabelled. The binding of the selected compound, [3H]-VUF 4576, to calmodulin was studied according to a recently described technique using CaM agarose. However, some peculiar results were obtained: the tight binding of [3H]-VUF 4576 increased in presence of cold VUF 4576, resulting in a high non-specific binding. The unexpected results could readily be explained by a high binding capacity of the labelled compound and the cold ligands to the walls of the test tubes used. Such results were also found when [3H]-chlorpromazine ([3H]-CPZ) was applied. In literature comparable findings have been published. To explain such results the influence of positive cooperativity or irreversible binding has been suggested. We suppose that not only in our study, but also in other published investigations, binding to glass of the radioligand and/or the cold compounds may have had a strong influence. We suggest, therefore, that care should be taken in interpreting non-classical displacement data obtained with ligands which combine a rather low affinity and a high degree of lipophilicity, not only for binding to calmodulin, but for other systems as well. PMID- 1297893 TI - The anxiogenic-like effects of pentylenetetrazole in mice treated chronically with carbamazepine or valproate. AB - The chronic effects of carbamazepine administration (5, 10, 20 mg/kg i.p. daily for 14 days) on the anxiogenic response to pentylenetetrazole were studied in the light/dark aversion test. In mice, these effects were compared with those of sodium valproate (100, 200 and 300 mg/kg i.p.), a putative anxiolytic drug, and lorazepam (0.025, 0.05 and 0.10 mg/kg i.p.), a well-established anxiolytic drug. The results showed that the anxiogenic-like behavior induced by subconvulsant doses of pentylenetetrazole (15 mg/kg i.p.) was antagonized by the chronic administration of lorazepam as well as sodium valproate, a GABA agonist. In fact, the increased aversion of mice for the light compartment of the light/dark box was reduced. Carbamazepine failed to significantly alter the anxiogenic-like behavior of mice. These findings provide further evidence for the absence of anxiolytic properties of carbamazepine and for a behavioral anxiolytic profile of valproate similar to that of benzodiazepines. PMID- 1297894 TI - Further metabolic studies of codeine and morphine in mice pretreated with sympathomimetics. AB - The effects of ephedrine and phenylpropanolamine (PPA) on the 24 h urinary excretion of morphine, codeine and their metabolites, and on the plasma and brain disposition of morphine and codeine at steady state in mice were studied. Morphine-3-glucuronide was the major urinary metabolite in morphine treated animals, while for codeine treated animals norcodeine and morphine-3-glucuronide were the major metabolites. In all cases percentage of drug excreted unchanged was 10-15% of the administered dose. Ephedrine or PPA pretreatment had no apparent effect on these parameters. The metabolic ratios for the different pathways were comparable in all treatment groups. Steady-state plasma and brain concentration-time profiles of codeine and morphine also showed marked similarity in all treatment groups. Apparently, ephedrine or PPA pretreatment has no effect on the disposition of morphine and codeine in mice. The results are discussed from the perspective of our earlier findings of dependence on cough mixtures containing opioids and sympathomimetics. PMID- 1297895 TI - Histamine leukocytosis. II. Source of histamine leukocytosis. AB - Leukocytes were labelled by intravenous injection of tritiated thymidine (3H thymidine) in dogs to discover the source of the increased number of neutrophils in the circulating blood after injection of histamine in beeswax. Dogs with normal hemograms were given 1.0 mCi/kg of 3H-thymidine alone, and in different sequences, with histamine in beeswax. When 3H-thymidine was given during maintained histamine leukocytosis, labelled granulocytes appeared in and disappeared from the blood earlier than in control tests and the number of labelled cells was greater in the histamine-treated animals. Administration of histamine in beeswax 3 days after injection of 3H-thymidine also induced the premature appearance and disappearance of labelled neutrophils in the circulating blood. It was concluded that leukocytosis induced by the chronic action of histamine is due to 1) stimulated proliferation and differentiation of neutrophil precursor cells in the bone marrow and 2) the release of mature leukocytes from the bone marrow. PMID- 1297896 TI - Pharmacokinetics and relative bioavailability of a new chewable, buffered acetylsalicylic acid tablet formulation in comparison to a conventional plain tablet. AB - The pharmacokinetics of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) following single dose administration of a new chewable, buffered ASA tablet formulation and a conventional plain ASA tablet formulation were investigated in 12 healthy male subjects. The volunteers received in a randomized, crossover design two pharmaceutical units of both formulations containing 500 mg ASA each after an overnight fast on an empty stomach. ASA and SA in the collected plasma and urine samples were determined using an internally standardized validated HPLC method. Regarding the normalized extent parameters for ASA, an increase of about 114% for the maximum concentration (Cmax,norm) and about 16% for the area under the curve (AUC0----infinity,norm) was found for the new chewable, buffered tablet formulation as compared to the plain tablet. Comparing the corresponding parameters for the main metabolite, both formulations were statistically equivalent. The quotient of normalized areas (QAUC0-20min, norm/AUC0----infinity,norm) for ASA was higher by about 124% for the new formulation, indicating an increased and faster absorption during the first 20 min after administration. The time of the concentration maximum did not differ statistically. These data indicate that the new chewable, buffered ASA tablet formulation shows a significant benefit as compared to the plain ASA tablet. The new tablet produced higher plasma ASA concentrations in a shorter time, which is clinically important since higher ASA concentrations are assumed to be related to an improved analgesic efficacy. PMID- 1297897 TI - Introduction. Rethinking HIV prevention: critical assessments of the content and delivery of AIDS risk-reduction messages. PMID- 1297898 TI - AIDS and promiscuity: muddles in the models of HIV prevention. AB - AIDS has been blamed on promiscuity and the promiscuous, and a major goal of many HIV-prevention programs has been to induce people to reduce the number of their sexual partners. Despite the salience of this concept in the AIDS discourse of scientists, policymakers, the media, religious leaders, and the gay community, critical analysis of the role of promiscuity in this epidemic has been lacking. Following a review of promiscuity in various genres of AIDS discourse, this article discusses promiscuity in American society and in HIV-prevention campaigns. The relative risks associated with monogamy, abstinence and promiscuity are examined, and the author concludes that the partner-reduction strategy, instead of contributing to a reduction in HIV transmission has been an impediment to AIDS prevention efforts, exacerbating the problem by undermining the sex-positive approaches to risk reduction that have proven effective. Responsibility for this misguided strategy is attributed to a moralistic approach to AIDS and to the misapplication of epidemiological concepts and inappropriate social science models to the task of promoting healthy forms of sexuality. PMID- 1297899 TI - AIDS, sex and condoms: African healers and the reinvention of tradition in Zaire. AB - Condoms offer considerable protection against sexual transmission of AIDS. Yet many Africans who are at risk of infection reject condoms as "unnatural." Data from Zaire have been used to examine this culturally constructed category in relation to sexuality, procreation, gender roles, class formation and international health and development policy. Much more than a simple transfer of biomedical technology is involved. Condom use with regular partners raises issues of cultural politics at many levels. "Traditional" African healers represent important social networks with considerable authority in poor urban communities. They are able to reinterpret cultural categories and endow behavior with new meanings. Action-research in Kinshasa was used to explore roles that healers might play in promoting change to safer sex practices. PMID- 1297900 TI - HIV prevention: a dramaturgical analysis and practical guide to creating safer sex interventions. AB - Safer sex is currently a major strategy for preventing HIV transmission. We examine safer sex interventions using an interactionist form of dramaturgical analysis. This approach yields a dynamic model with which to generate novel safer sex interventions highly sensitive to changing individual, cultural, and social variables. Our goal is to help medical anthropologists, applied social scientists, health educators, community outreach specialists, and those who are sexually active apply safer sex strategies more effectively. PMID- 1297901 TI - AIDS and the i.v. drug user: the local context in prevention efforts. PMID- 1297902 TI - Sex, drugs and videotape: the prevention of AIDS in a New York City shelter for homeless men. AB - This paper documents a process of social change through participant observation. During the course of research a group response was facilitated by a team of residents, staff and researchers. The social context, a shelter for homeless men in New York City, will be presented first, emphasizing those aspects of resident living that are germane to HIV transmission. Next, we describe the group response, the creation of a video. This activity gave numerous insights to the investigators into how the men perceived the homeless state and something of their relationships to others within and outside the institutions. In particular, their views on women and sex were expressed in the video. The insights gained by the men and the investigators are analyzed in terms of a self-help strategy which was effective in conveying information about HIV transmission and prevention. PMID- 1297903 TI - Alcohol and risky sex: in search of an elusive connection. AB - Since the publication of the 1986 article by Stall, McKusick, Wiley, Coates and Ostrow, the conclusion that drinking alcohol prior to or during erotic encounters increases the probability of engaging in high-risk sexual behavior has been widely accepted, despite some contradictory findings from research on this hypothesis. This paper presents the results of tests of the alcohol/risky-sex hypothesis in a cohort of gay men in Flanders, Belgium. Failing to find evidence to support the hypothesis of a general effect of alcohol on sexual risk taking, we argue that previous conclusions on this matter must be viewed with extreme caution, especially in light of the implications that this failure to replicate has for AIDS prevention programs. Cultural, social, and methodological factors that could account for this failure to replicate are discussed in the context of a review of the literature on this hypothesis. PMID- 1297904 TI - [New hope for more than half a million Italians who suffer from epileptiform disorders]. PMID- 1297905 TI - [The fragile X chromosome and psychiatry]. AB - The importance of X fragile chromosome in mental retardation is outlined. Two male patients with a low IQ are studied. They were brothers and their mother too was non mental retarded cytogenetically X fragile positive. PMID- 1297906 TI - [Pathology of adaptation according to Sami-Ali and index of conformity to the Rorschach test in ulcerative rectocolitis]. AB - According to Sami-Ali's theoretical model the psychosomatic personality is characterised by an adaptation pathology whose main elements are the repression of imaginative thought and conformity to socio-cultural standards. This study examines adaptation pathology using the Rorschach test. The Authors have formulated a conformity index by relating kinestheses (M) and banal perceptions (BAN). The study was carried out on a sample of 41 patients suffering from ulcerous rectocolitis comprising 24 males and 17 women with a mean age of 32 years. As expected in the hypothesis 97.6% of the sample showed M values below the norm, and 68.3% had Ban values higher than normal, whereas the conformity index was positive and tendentially positive in 65.9% of cases. These findings confirm Sami-Ali's theory. Subjects with ulcerous rectocolitis form part of the adaptation pathology which characterised the psychosomatic personality, with an inverse proportionality between imaginative activity (kinesthesia below normal) and conformism (banal perceptions above the norm). PMID- 1297907 TI - [The prophylaxis of benzodiazepine withdrawal syndrome in the elderly: the effectiveness of carbamazepine. Double-blind study vs. placebo]. AB - A double-blind study was performed to evaluate carbamazepine for the prophylaxis of benzodiazepine withdrawal syndrome in elderly patients--a controversial subject despite the extensive use of such drugs in old age. Thirty-six outpatients aged > or = 60 yrs suffering from general anxiety disorders and benzodiazepine abuse underwent gradual discontinuation of benzodiazepine therapy in two groups, one treated with carbamazepine and one with placebo. The carbamazepine-treated group demonstrated a lower incidence of withdrawal symptoms rated according to the Physician Withdrawal Check List (p < 0.01), better results with the Hopkins Symptom Check List (Covi cluster, p < 0.01) and a more markedly reduced score with the Hamilton Rating Scale for Anxiety (p < 0.05). Only 3 out of 18 patients in said group complained of side effects attributable to carbamazepine, which disappeared at lower dosages. PMID- 1297909 TI - [Psychological reactions of medical staff to the patients infected with HIV-1]. AB - This paper describes the relationship between medical staff and HIV-1 patients. Important mechanisms can be used by individuals with HIV-1 infection in order to accept their seropositivity to HIV-1. Among them, regression and negation are well-known. These mechanisms are related to countertransference lived by the medical staff. They are various as well as rejected by medical staff to avoid anxious reactions. On the contrary, the medical staff has to accept the experiences of the patients and to be ready to listen to the problems of HIV-1 infected people. PMID- 1297908 TI - [Bipolar disorder: clinical trials with fluoxetine]. AB - Sixty patients (39 females and 21 males) aged between 20 and 65 (average 48.5) with bipolar disorder in the depressive phase, according to the DSM III-R diagnostic criteria, were treated with fluoxetine (20-60 mg/die) for 8 weeks. Evaluation of therapeutical efficacy was performed at 0 time and after 14, 28, 42, and 56 days, using the following psychometric tests; HAM-D, SCL-90, CGI. At the end of treatment 42 patients (70%) showed a reduction of the HAM-D score over 50%. Clinical results suggest that fluoxetine is affective in bipolar disorder. Tolerability was judged good and very good in 76% of patients. Side effects were very mild and in any case of rapid regression. PMID- 1297910 TI - [Psychiatric emergency and first level intervention. Analysis of a series of attempted suicides at a Turin First Aid station]. AB - The present study was carried out in a Turin Hospital and considers interventions for attempted suicide in the period March-May 1988, examining psychopathological and social characteristics. No epidemiological evaluation was made of the problem but rather an analysis of the specialist and general assistance given to these patients in First Aid structures, the therapeutic protocols that preceded the attempted suicide, motivations and modalities involved. In addition, a three month follow-up looked at the therapeutic destiny of the cases. In the last analysis, an attempt was made to evaluate the therapeutic interaction between local psychiatric services and the First Aid facility of a general hospital: in fact, according to the health service reform law and the application of Law 180, the DEA, as a hospital structure, forms part of the structures delegated to the treatment of mental disturbances. PMID- 1297911 TI - [Survey of hospitalization in a mental health service during the ten- year period 1981-1990]. AB - The paper reports the findings of a 10-year statistical survey of the users and activities of the Mental Health Service Of S. Giovanni in Fiore (Cosenza). The incidence of booth voluntary and TSO hospitalisation is reported in relation to users and with reference to the Centre's activity during other periods. PMID- 1297912 TI - The oligosaccharide of Haemophilus influenzae. PMID- 1297914 TI - Characteristics of the internalization and intracellular survival of Campylobacter jejuni in human epithelial cell cultures. AB - The characteristics associated with the internalization and intracellular behavior of Campylobacter jejuni during short-term and long-term cultivation with INT 407 cells were examined. The internalization of C. jejuni by INT 407 cells was inhibited by cytochalasin dansylcadaverine, chemicals that disrupt microfilament formation and inhibit receptor cycling, respectively. Ammonium chloride and methylamine, two chemicals that inhibit endosomal acidification, did not affect C. jejuni internalization. Once internalized, C. jejuni were found exclusively with membrane-bound vacuoles. With regard to intracellular survival, a decline in the number of viable intracellular bacteria, as determined by protection from gentamicin, occurred during the initial phase of infection and when a low level of the antibiotic was maintained in the culture medium. However, the number of intracellular C. jejuni increased markedly after the removal of the antibiotic. In the absence of antibiotic, the infection led to the deterioration of the cell monolayers, indicating that C. jejuni is able to survive within epithelial cells and elicit a cytotoxic effect. The ability of C. jejuni to enter and exert deleterious effects on cells may reflect a pathogenic mechanism associated with enteritis caused by this organism. PMID- 1297913 TI - Analysis of pneumococcal PspA microheterogeneity in SDS polyacrylamide gels and the association of PspA with the cell membrane. AB - Pneumococcal surface protein A (PspA) is a protection-eliciting surface protein found on all pneumococci. Although highly cross-reactive, it displays interstrain variation in its size and in the expression of individual antibody reactive epitopes. PspA was not released in significant amounts from pneumococcal membranes treated with sodium carbonate, but was solubilized with SDS. Thus, PspA is either an integral membrane protein or is attached to an integral membrane component. By SDS-PAGE and immunoblot analysis, we found two predominant molecular sizes of PspA in each strain examined. The smaller band was about the size expected from the inferred amino acid sequence of PspA and the larger band appeared to be a dimer of the monomer PspA. When higher concentrations of lysate were run on SDS gels, it was also possible to detect many additional high molecular weight components that reacted with antibodies to PspA. These multiple high molecular weight PspA bands were not due to the attachment of PspA to peptidoglycan or teichoic acids, did not appear to be composed of degraded PspA and most likely resulted from non-covalent polymerization or aggregation of PspA. PMID- 1297915 TI - Roles of different putative colonization factor antigens in colonization of human enterotoxigenic Escherichia coli in rabbits. AB - The role of some well-characterized putative colonization factors (PCFs) in enterotoxigenic Escherichia coli (ETEC), i.e. PCFO159, PCFO166, CS7, CS17 and CFA/III, for colonization of the bacteria in the intestine was studied in a non ligated rabbit intestine model (RITARD). Intestinal administration of 10(11) organisms of the various strains only resulted in very mild symptoms with loose stools during a few days in most of the animals. Strains expressing PCFO159, CS7, CS17 and CFA/III were shed in the stool for a significantly longer period than PCF/CS-negative ETEC. However, the mean time of shedding PCFO166 positive organisms did not significantly exceed that of non-fimbriated E. coli. All strains that colonized rabbit intestine, as assessed by prolonged fecal excretion, also gave rise to high serum antibody responses against the homologous fimbriae whereas non-colonizing strains failed to induce such responses. This study strongly suggests that several of the recently described PCFs, e.g. PCFO159, CS7, CS17 and CFA/III are colonizing factors and strong immunogens. PMID- 1297916 TI - Infection of Macaca radiata with viruses of the tick-borne encephalitis group. AB - Our studies confirmed the susceptibility of Macaca radiata (bonnet macaques) to Kyasanur Forest disease (KFD) and enabled us to demonstrate KFD virus-specific gastrointestinal and lymphoid lesions. Significant histopathological changes occurred in the small and large intestine, spleen and lymph nodes; and viral antigens were found in these same organs by immunohistochemistry. Viral antigen positive cells were always associated with histological evidence of necrosis, which suggests that cell death occurred directly from viral replication or secondarily from attack by immune mechanisms. In contrast, M. radiata infected with Omsk virus did not show any signs of clinical disease, and no virus could be isolated from tissues or blood at the end of the experiment. However, M. radiata infected with Russian spring-summer encephalitis (RSSE) developed clinical signs in the central nervous system; and, in one monkey, RSSE virus was isolated from the brain, and viral antigen was localized in neurons. Our data indicate that M. radiata is an excellent model to study human disease caused by KFD virus and could serve as a model for human disease caused by other, related strains of this group of viruses. PMID- 1297917 TI - Introduction of Francisella tularensis at skin sites induces resistance to infection and generation of protective immunity. AB - Mice are susceptible to systemic infection with Francisella tularensis strain LVS; thus, the intraperitoneal (i.p.) lethal dose at 50% (LD50) in C3H/HeN and C57BI/6J mice is only a single bacterium, while the intradermal (i.d.) LD50 is more than 10(4). Here we show that the LD50 when LVS is introduced via the skin, either i.d. or subcutaneously (s.c.), ranges from 7 x 10(4) to 2 x 10(6). Sublethal i.d. or s.c. infection (priming) invariably leads to the generation of systemic and specific protective immunity: primed mice survive lethal i.p., intravenous (i.v.), or i.d. challenges of LVS but not Salmonella typhimurium W118 or Escherichia coli 018:K1:H7 strain BORT. PMID- 1297918 TI - [Incidence and evolution of retinopathy of prematurity. A six year experience in a neonatal intensive care unit]. AB - The incidence and the evolution of ROP in 324 infants with birthweight < or = 2500 g is report. The highest incidence was among the 750 and 1250 g birthweight infants. 5 infants < 750 g survived without signs of ROP. When present the ROP was within the 3rd stage and had a favourable outcome: spontaneous resolution without cicatricial lesions. PMID- 1297919 TI - [Suicidal behavior among adolescents]. AB - Some data from the literature on adolescent suicidal behaviour are reported: incidence, employed methods, warning signs, risk factors, some psychodynamic aspects. The purpose of this work is to contribute to the study on this matter by a research on 33 adolescents (12 males, 21 females: mean age 14 years, range 11.2 17 years) examined because of suicidal behaviour. The study method includes: anamnesis, psychodiagnostic inquiry, family and environmental investigation, psychiatric evaluation. Suicidal behaviour is characterized by low levels of determined self-elimination intent ("suicidal gestures") in 36% of cases (1 male, 11 females). Relapses are found in 35% of cases, with death in 1 case. The most frequently used methods is drug poisoning (65%). Most common place where suicidal behaviour takes place is at home (82%). Most show warning signs especially verbal threats. Some problem in the family situation (conflicts in the parental couple or between parents and children, psychopathologic disturbances in the parents) and frequent difficulties in school and social adjustment are evident. In 45% a depressed state was noted, in the other cases several psychopathologic disturbances have been found: hysteric neurosis, borderline personality, psychosis. In 30% of cases symptoms coexist with a self-injuring meanings (nervous anorexia, pseudo-epileptic seizures). Prevalent psychodynamic characteristics are: vulnerability in facing frustrating situations and research of support from inadequate parental figures: displacement from hetero-direct aggressive drives to an expiratory or revengeful self wounding behaviour. Some criteria for an emergency care and for a middle to long term treatment are mentioned, and the opportunity for collaboration between pediatricians and psychotherapists is suggested. PMID- 1297920 TI - [Vitamin D prophylaxis in childhood]. AB - The past 10 years have seen a return of rickets. Clinical and/or biochemical signs of vitamin D deficiency are still found in some children and adolescents, mainly during the winter. Sunlight exposure is able to prevent vitamin D deficiency and rickets but the dramatic influence of changes in solar ultraviolet B radiation on cutaneous vitamin D3 synthesis, related to latitude and season effects, suggest that a vitamin D supplementation may be advisable. Moreover, human milk and common foods contain low quantities of vitamin D. So, we recommend routinely 400 IU of supplementary vitamin D per day in all infants. The vitamin D requirements in low-birth-weight infants are higher than at term infants; it is recommended the use of 1000-1600 IU per day in the first months of life. Intermittent high-dose of vitamin D and vitamin D metabolites are not advisable for prophylaxis of rickets. PMID- 1297921 TI - [A new device for phototherapy of neonatal jaundice]. AB - The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested. PMID- 1297922 TI - [Bullous mastocytosis. Two clinical cases]. AB - Two cases of bullous mastocytosis in children are described. This form must be differentiated from the more common mastocytosis with bullae: in the latter form, blisters occur on previously existing papillar or nodular lesions, whereas in bullous mastocytosis the blisters occur on apparently normal skin. PMID- 1297923 TI - [Schoenlein-Henoch syndrome and salmonella infection: a new association?]. AB - Schoenlein-Henoch's disease has a immunological pathogenesis (mediated by immunocomplexes), is characterised by a number of differently associated signs and symptoms, and leads to the possible involvement of the cutis, joints, abdomen and kidneys. Two cases of Schoenlein-Henoch's disease associated with acute salmonella enterocolitis were recently brought to our attention. In two girls, aged 2 years and 8 months and 13 months respectively, the onset of diarrheic alvus was followed, after an interval of 4-5 days, by the sudden appearance of pompho-erythemato-hemorrhagic and petechial cutaneous lesions localised symmetrically on the extensor surfaces of the lower limbs and buttocks, and accompanied in the first case by intense abdominal pain and in the second by diffuse arthralgia, with predominant involvement of the tibio-tarsal joints. Laboratory tests showed slight alterations of phlogosis indexes and high levels of serum IgA (182 and 204 mg/dl respectively). The examination of feces showed the presence of occult blood and salmonella (belonging to C and D groups respectively) were isolated in the coproculture. Other culture and serological tests carried out while in hospital were negative. The clinical manifestations gradually resolved within the space of two weeks following the normalisation of the alvus obtained after a few days using dietary regulation. After two months the girls were found negative on clinical examination; in the second case described there was a positive response to Widal's reaction with high antibody titres against both O and H antigens, whereas the coproculture continued to be positive for Salmonella.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297924 TI - [A case of multiple deformities: upper harelip, tubercles of the auricle, anus in vulva]. AB - The case presented of a newborn with multiple deformities: preauricular tubercles, left auricular roof deformity, labicachisis of the right upper lip, dermoid-type swelling on the left eye, deep labial fold at the left commissure and "forked" anus in vulva. Though the combination does not exactly match any syndrome, it has various points in common with Goldenhar's syndrome, of which it might be a phenotype variant. The single cause of the malformations might be an early (microvascular) disturbance of the primary segments in growth areas surrounding the cephalic and caudal segments, first of the medullary plate and subsequently of the primary medullary canal. PMID- 1297925 TI - [Neonatal hemorrhagic syndrome with unfavorable prognosis]. AB - The Authors describe a case of neonatal hemorrhagic syndrome associated with a large hemangioma on the left lower limb with an unfavourable prognosis. The clinical, biohumoral and anatomicopathological characteristics indicate a Kasabach-Merrit syndrome (SKM) with massive platelet sequestration in the large hemangioma. The pathogenetical mechanisms of SKM and the medical surgical and radiant therapy are mentioned. The Authors also discuss the various diagnostic problems imposed by the presence of serious hemorrhagic pathology at neonatal age. PMID- 1297926 TI - Calcium accumulation in synapses of the rat hippocampus after cerebral ischemia. AB - The ultrastructural localization of calcium deposits in the synapses of rat hippocampus after 10 min global cerebral ischemia was evaluated. Oxalate pyroantimonate technique was applied. After 24 hours of postischemic recirculation enhancement of intracellular (pre- and postsynaptic parts) and extracellular (synaptic clefts) calcium deposits was found in great proportion of synapses in CA1 sector. Abundant Ca-precipitates appeared specially in synaptic clefts and in the postsynaptic parts near synaptic densities. Increased calcium deposits in some changed mitochondria were also observed. The results presented in this paper suggest synaptic modulation of Ca2+ homeostasis, disturbed after ischemic incident. Presence of Ca-precipitates in synaptic clefts and postsynaptic parts seems to be a sensitive indicator of increased calcium influx from the extracellular to the intracellular compartments. PMID- 1297927 TI - Changes in endogenous prostacyclin in the rat brain during clinical death and after resuscitation. AB - By means of the radioimmunologic method changes of concentration of 6-keto prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3 fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed. PMID- 1297928 TI - Neuropathological changes in resected temporal lobe of patients with cryptogenic epilepsy. AB - The study was performed on cerebral tissue resected during temporal lobectomy in 16 patients whose long-standing cryptogenic epilepsy did not submit to anticonvulsive drugs. Cases presenting definite etiological factors such as CNS trauma, infection or neoplasm were excluded. Neuropathological investigations disclosed microangiomas and focal vascular malformations in the meninges and tissue in 7 patients. Neuronal heterotopias in the white matter and of the white matter in the cortex were observed in 3 cases. Main cortical changes were: neuronal loss, chronic neuronal degeneration, perineuronal satellitosis, and GFAP positive submeningeal gliosis, especially at the bottom of sulci, perivascular gliosis and laminar or diffuse gliosis. The changes in the hippocampus were most enhanced in the end-plate and in the sector H3 of the pyramidal layer. Astrocytic gliosis in the white matter presented distinct GFAP and S-100 immunostaining; the latter involved in some cases a wider area than the GFAP reaction. The above named changes are analysed with regard to the presumed epileptogenic factors and to the postepileptic damage. PMID- 1297929 TI - Influence of aging on the protein profile of myelin isolated from human brain white matter. AB - Myelin proteins composition was examined in material of 20 autoptic cases at ages from 20 to 97 years. The technique of polyacrylamide gel electrophoresis and isotachophoresis was applied. In polyacrylamide gel electrophoresis a progressive increase starting at the age of 60 years of Wolfgram protein at the expense of Folch-Lees proteolipid protein and DM-20 protein was observed. The myelin associated protein started to increase in the 4th and 5th decade of life, returning thereafter to values observed in younger cases. The isotachophoretic technique did not differentiate the changes observed in myelin protein in the course of aging. PMID- 1297930 TI - Cerebral ganglioglioma with long history and unusual prominence of the mesenchymal elements. Case report. AB - A case of cerebral ganglioglioma, a relatively rare and controversial tumor of the central nervous system, is reported. The histological pattern of the tumor consisted of differentiated neuronal cells and glial elements displaying a various extent of cytologic abnormalities. Beside these two typical components for ganglioglioma, an abundance of collagen fibrils and numerous blood vessels were encountered. The long clinical course manifested by temporal epilepsy preceding clinical diagnosis of brain tumor and peculiar histological appearance seem to be of considerable interest. PMID- 1297931 TI - Comparative anatomy of the arterial vascularization of the hippocampus in man and in experimental animals (cat, rabbit and sheep). AB - The studies were performed by the authors' injection method on 30 human brains and 80 animal ones. The cerebral arteries were injected with synthetic coloured latex and then prepared in an operating microscope. It was found that the main source of arterial supply of both the human and animal hippocampus is the posterior cerebral artery. However, this artery has different origins in the arterial circle of the brain in man, cat, rabbit and sheep. Comparative investigations have also proved that the hippocampal vascular system in man and animals is very similar. It is formed by branches of the posterior cerebral artery and of the anterior choroidal artery, called the hippocampal arteries, and by numerous internal hippocampal arterioles arising from them at right angle. The regional distribution of these arterioles is impossible to describe because of their variable course in the hippocampal cortex and of the similar vascularization of different cortical areas of the hippocampus. The studies have also shown that the hippocampal arterial system is very well developed and makes collateral circulation possible. Extracerebral segments of the hippocampal arterioles in human senile brains, and chiefly in brains with atherosclerosis, showed different deformations in the form of siphon-like structures, knot-loops and vascular glomeruli. PMID- 1297932 TI - Perinatal damage of brain stem depending on the maturity of its structures. AB - The aim of this study was to discuss the interaction between the maturation of the brain stem and its susceptibility to perinatal lesion. Many observations indicate that the last months of pregnancy and the perinatal period are the time of intensive maturation of these structures. Lesions of the brain stem were many times found after acute anoxia as well as after chronic asphyxia during this period. This indicates the importance of prevention of the pathology of pregnancy. Occurring in the last trimester of gestation it can induce damage of brain stem centers important for the fetus to survive the stress of birth and adaptation for individual life. PMID- 1297933 TI - Lectin histochemistry and alkaline phosphatase activity in the pia mater vessels of spontaneously hypertensive rats (SHR). AB - Some lectins were used to study the localization of sugar residues on the endothelial cell surface in the pia mater blood vessels of control (WKY) and hypertensive rats (SHR). The lectins tested recognized the following residues: beta-D-galactosyl (Ricinus communis agglutinin 120, RCA-1), alpha-L-fucosyl (Ulex europaeus agglutinin, UEA-1), N-acetylglucosaminyl and sialyl (Wheat germ agglutinin, WGA), N-glycolyl-neuraminic acid (Limax flavus agglutinin, LFA), and N-acetyl-D-galactosaminyl (Helix pomatia agglutinin, HPA). Several differences were revealed in the presence of sugar receptors on the surface of endothelial cells between the control and the hypertensive rats. Our studies showed also differences in the localization of the tested glycoconjugates between pial capillaries, small, medium-size and large pial arteries. The histochemical evaluation of alkaline phosphatase revealed an increased activity of the enzyme in the pial vessels of SHRs as compared with control rats with a similar localization of the enzyme activity. Some differences in the distribution of lectin binding sites and alkaline phosphatase activity could be associated with the different functions of particular segments of the pial vascular network. PMID- 1297934 TI - The health and mental health of New Zealand Vietnam war veterans with posttraumatic stress disorder. AB - AIM: To examine the extent of posttraumatic stress disorder (PTSD) in a sample of New Zealand Vietnam veterans and to compare the pattern of health and mental health between veterans classified as posttraumatic stress disorder cases and non cases. METHOD: Five hundred and seventy-three randomly selected male Vietnam veterans participated in a mailed survey. The questionnaire assessed several mental health dimensions and a number of components of physical health. Demographic and military service details were also gathered. RESULTS: The study classified 12% of the sample of veterans as suffering from posttraumatic stress disorder. The posttraumatic stress disorder group differed from the non posttraumatic stress disorder group on all measures of physical and mental health. They reported higher symptom scores, more disability days, lower self rated health and made more frequent contacts with health care providers. They also experienced greater anxiety, depression and loss of control, and lower wellbeing. Significant differences on some demographic and military service measures were also found between the groups. CONCLUSIONS: A number of New Zealand Vietnam veterans may be classified as exhibiting the symptoms of posttraumatic stress disorder, with the proportion being comparable to rates found in US studies. Veterans with posttraumatic stress disorder experience significantly poorer physical and mental health. Combat experience in Vietnam appears to contribute to posttraumatic stress disorder level. It is suggested that posttraumatic stress disorder may be under-utilised as a diagnostic category because it may coexist with depression or anxiety states and that physicians should be attentive to military service as an indicator of posttraumatic stress disorder. PMID- 1297935 TI - A comparison of elderly patients with proximal femoral fractures and a normal elderly population: a case control study. AB - AIM: To assess the importance of bone density and other risk factors in elderly subjects with hip fractures. METHOD: Thirty-six subjects with femoral neck fracture were compared with 72 community controls in this case control study. Variables compared included: history of falls, previous fracture, body mass index, hand grip strength, blood pressure, medication use, cigarette smoking, alcohol intake, visual acuity, age at menopause, mental status quotient, mobility index and mid thigh circumference. Bone mineral density was measured at the hip (DPA absorptiometer) in the 36 subjects with hip fracture and 36 community controls. RESULTS: Fracture patients had significantly (p < 0.01) reduced bone mineral density at femoral neck (0.64 vs 0.74 g/cm2) and trochanteric regions (0.55 vs 0.66 g/cm2). They also had significantly (p < 0.05) lower body mass index, weaker hand grip strength, smaller mid thigh circumference, reduced mobility and more previous fractures. After controlling for age and sex stepwise logistic regression identified handgrip strength, mobility status and falls in that ranking as risk factors for fracture. Bone mineral density was correlated with mobility status and grip strength. CONCLUSION: Patients with hip fracture have lower bone mineral density than controls. Mobility, grip strength and muscle bulk appear to be important in fracture aetiology and could operate either through bone density or risk of falling. PMID- 1297936 TI - The pathogenesis of vesicoureteric reflux and reflux nephropathy--what are we learning from antenatal ultrasonography? PMID- 1297937 TI - Melanoma incidence and trends in the Nelson-Marlborough area of New Zealand. AB - AIMS: To determine the recent incidence of melanoma in the Nelson-Marlborough area of New Zealand and to compare this with a formerly determined incidence from the same area and with published incidences and trends elsewhere in New Zealand and Queensland. METHODS: All histopathology reports for the region were examined retrospectively each four weeks and relevant information extracted. In cases of doubt, pathologists were consulted and cases reviewed. Population, demographic and weather information was obtained from statistical records. RESULTS: These showed a doubling of the incidence since the previous survey with a reduction in female incidence. There was marked reduction in the incidence in the age groups 20-39 with an increase in those over 60 years. The number of superficial more easily cured lesions were almost doubled with marked reduction in the more sinister thicker and nodular lesions. CONCLUSIONS: The incidence of melanoma in the region is increasing at a rate comparable with other areas but with significant reductions in the incidence of thicker and more advanced melanoma as well as a decreased incidence in those under 40 years of age. The incidence in Nelson-Marlborough still remains very high but is slightly less than that shown for the Tauranga district over a similar period. PMID- 1297938 TI - Cervical screening: what do Auckland general practitioners do? AB - AIMS: To assess the frequency of cervical screening; average age of screened women and adequacy of decontamination practices of vaginal specula by Auckland general practitioners. METHODS: A random sample of 96 Auckland general practitioners completed a questionnaire at the time of consultation describing the screening history and decontamination practices for vaginal specula from five consecutive patients having a cervical smear test. RESULTS: Of the 96 doctors 68 completed the questionnaire for the five consecutive patients. The majority of women were aged below 50 years and the median time since the last smear for women with a previously normal smear was 18 months. Although the majority of doctors adhered to Health Department guidelines for decontamination, deviations occurred by: reusing plastic specula; using only disinfection as a means of decontamination and not boiling specula for 30 minutes. CONCLUSIONS: The majority of women being screened are young and there is a high level of very frequent screening in women with previously normal smears. Closer adherence to the 1991 cervical screening recommendations and Health Department guidelines for decontamination of vaginal specula is required for some Auckland general practitioners. PMID- 1297940 TI - Analysis of injury and death from burning upholstered furniture. AB - AIMS: Upholstered furniture is considered by governments in the United Kingdom, United States of America, Canada and New Zealand to be a potentially hazardous product. Use of polyurethane foam in upholstered furniture in the United Kingdom was banned in 1989 so as to reduce the risk of injuries and deaths from fire. This study assessed the situation in New Zealand. METHODS: Burn related deaths (1977-86) and injuries (1986) from the Health Statistics Services hospitalisation records were examined to identify cases in which upholstered furniture and bedding were implicated and analysed to describe the situation. Coroners files where relevant were examined. Detail on all fires and domestic fires for 1987 obtained from the New Zealand Fire Service were also examined. Characteristics of upholstered furniture available in New Zealand during the 1987 production year were identified through responses to a questionnaire sent to manufacturers, wholesalers and importers of this type of furniture. RESULTS: Examination of burn related deaths in which upholstered furniture and bedding were implicated (28.3% of all burn related deaths) showed the average annual death rate was at least 0.16 per 100,000 population and that the change in rate over ten years was not significant. Bedding and mattresses appeared to be the first textile items to ignite in 25.1% of those deaths occurring in the bedroom and furniture in 7.2% of those in the lounge. At risk groups were males (1.9 per 100,000 compared with 1.3 per 100,000 for females), those over 55 years (males 5.3, females 4.8 per 100,000) and those who may live alone (separated 4.5, single 5.4, divorced 11.4, widowed 13.4 per 100,000). The mix of alcohol consumption, smoking, then falling asleep created a situation of risk. Sufficient information was not always available to identify with certainty that upholstered furniture and/or bedding was the item to first ignite those fires which subsequently caused burn related injuries and deaths. Manufacturers, wholesalers and importers of upholstered furniture in New Zealand reported that of the total units, at least 38.5% had covers of wool/wool rich or leather and other materials which generally do not ignite readily. Polyurethane and polyester hollow-fill were commonly used as fillings. CONCLUSIONS: The death rate attributable to burning of upholstered furniture and bedding was not found to be especially high. Bedding, mattresses and bedroom furniture were reported more frequently than upholstered furniture. PMID- 1297939 TI - A comparison of efficacy and tolerance of the short acting sedatives midazolam and zopiclone. AB - AIMS: To compare the efficacy and tolerance of midazolam, 15 mg and zopiclone 7.5 mg once daily for seven days in a prospective, double blind trial of 88 patients, aged 18 or over, with sleep disorders in general practice. METHODS: Efficacy was evaluated using the Leeds sleep evaluation questionnaire (LSEQ). Adverse reactions were recorded as volunteered. RESULTS: fifty-one patients completed all aspects of the trial without violation of the protocol. Patients taking zopiclone improved in all aspects of the Leeds questionnaire (p < 0.01). Patients taking midazolam improved in six out of 10 items (p < 0.01). Rebound insomnia was evident in the zopiclone group in five out of 10 items of the LSEQ. Rebound was not evident in the midazolam group. There were no significant differences between midazolam 15 mg, and zopiclone 7.5 mg, in comparison between groups. Thirty-eight patients suffered 49 adverse drug reactions and there were no differences between the groups. CONCLUSIONS: Zopiclone 7.5 mg daily improved more items on the LSEQ than midazolam 15 mg daily but was associated with significant rebound insomnia. Adverse reactions were frequent with both drugs. PMID- 1297941 TI - Insulin dependent diabetes mellitus. PMID- 1297942 TI - Immunisation in the Nelson area. PMID- 1297943 TI - Medical insurance accessibility. PMID- 1297944 TI - Fluoridation and fractures. PMID- 1297945 TI - Hepatitis B survey at a health camp. PMID- 1297946 TI - Protection of the gastric mucosa from NSAIDs. PMID- 1297947 TI - Bed sharing or iron supplementation as a cause of cot death? PMID- 1297949 TI - Health goals and responsibility of patients. PMID- 1297948 TI - ASH. Selective acronym? PMID- 1297950 TI - General practice and the economy. PMID- 1297951 TI - Mupirocin-resistant S aureus in Auckland. PMID- 1297952 TI - The leucocytozoidae of South African birds: Caprimulgidae, Columbidae, Gruidae and Spheniscidae. AB - Four species of Leucocytozoon, L. caprimulgi of the Caprimulgidae (nightjars), L. marchouxi of the Columbidae (pigeons and doves), L. grusi of the Gruidae (cranes) and L. tawaki of the Spheniscidae (penguins) are re-described. Leucocytozoon turtur is declared a synonym of L. marchouxi. PMID- 1297953 TI - The Leucocytozoidae of South African birds: Passeriformes. AB - The leucocytozoids of ten families of Passeriformes--Estrildidae, Fringillidae, Laniidae, Nectariniidae, Passeridae, Ploceidae, Promeropidae, Pycnonotidae, Sturnidae and Zosteropidae--are reviewed. Leucocytozoon roubaudi from the Estrildidae, L. fringillinarum from the Fringillidae, L. balmorali from the Laniidae, L. gentili from the Passeridae, L. bouffardi from the Ploceidae, L. brimonti from the Pycnonotidae and L. zosteropis from the Zosteropidae are re described. Leucocytozoon dutoiti, L. nectariniae, L. deswardti, L. pycnonoti and L. sturni are new species described from the Fringillidae (Carduelinae), Nectariniidae, Promeropidae, Pycnonotidae and Sturnidae respectively while L. monardi is considered to be a synonym of L. gentili and L. molpastis is considered to be a synonym of L. brimonti. PMID- 1297954 TI - A light microscopical study of the intestinal tract of the Nile crocodile (Crocodylus niloticus, Laurenti 1768). AB - Although the histology of the intestinal tract of Crocodylus niloticus is touched on in overall studies on reptilian intestinal tract, a more comprehensive light microscopical study on this area is lacking. Specimens for histological examination were taken from the duodenum, the jejunum, the ileum and the rectum. The data obtained revealed that the mucosa is thrown into folds and simple, slightly branched tubular intestinal glands. The mucosal folds diminished in height and eventually disappeared upon reaching the ileorectal junction. The epithelium covering the folds and crypts was of the simple columnar type. Clear marginal cells, goblet cells and argentaffin cells were observed throughout the intestinal tract. No Paneth cells were seen in this study. The lamina propria was rich in lymphocytic infiltrations while the muscularis mucosa consisted mainly of an outer longitudinal layer, the inner circular layer being rudimentary or absent. The submucosa was extremely narrow, and the circular and longitudinal layers of the tunica muscularis contained distinct layers of dense fibrous connective tissue. The histology of the intestinal tract of C. niloticus is shown to be in line with the situation in crocodilians and also exhibits a resemblance to that of carnivorous mammals. PMID- 1297955 TI - Arthropod parasites of springbok, gemsbok, kudus, giraffes and Burchell's and Hartmann's zebras in the Etosha and Hardap Nature Reserves, Namibia. AB - A total of 48 springbok, 48 gemsbok, 23 kudus and 6 giraffes were examined for ticks and lice, while 9 Burchell's zebras and 6 Hartmann's mountain zebras were examined only for ticks. Springbok and gemsbok were shot in both the Etosha National Park in the north and the Hardap Nature Reserve in the south of Namibia. All the other animals were shot in the Etosha National Park. A total of 7 ixodid tick species and 8 lice species were recovered. The springbok carried few ticks. The adults of a Rhipicephalus sp. (near R. oculatus) were most numerous on the gemsbok, especially during November. The kudus were the only animals harbouring Rhipicephalus zambeziensis. Adult Hyalomma truncatum, followed by adult Hyalomma marginatum rufipes, were most abundant on the giraffes and adult Rhipicephalus evertsi mimeticus were commonest on the zebras. PMID- 1297957 TI - Parasites of domestic and wild animals in South Africa. XXXI. Adult ixodid ticks on sheep in the Cape Province and in the Orange Free State. AB - Four to 10 Dorper sheep on each of 12 farms in the Cape Province and 3 farms in the Orange Free State were examined for adult ixodid ticks at approximately 2- to 4-weekly intervals over periods varying from 4 to 18 months, commencing during January, February or April 1989. The farms in the Cape Province were located in the north-west, south-west and south of the province. Those in the Orange Free State were situated in the north-east and in the south. The sheep in the Cape Province harboured 10 species of ixodid ticks and the seasonal abundances of Ixodes rubicundus, Rhipicephalus evertsi evertsi, Rhipicephalus gertrudae and Hyalomma truncatum were determined. The animals in the Orange Free State were infested with 7 tick species and the seasonal abundances of I. rubicundus, R. evertsi and Hyalomma marginatum rufipes were determined. PMID- 1297956 TI - Parasites of domestic and wild animals in South Africa. XXX. Ectoparasites of kudus in the eastern Transvaal Lowveld and the eastern Cape Province. AB - Sets of four kudus were shot and examined for arthropod parasites at approximately monthly intervals from April 1981 to March 1983 in the southern part of the Kruger National Park, eastern Transvaal Lowveld. These animals harboured 10 ixodid tick species of which Boophilus decoloratus followed by Amblyomma hebraeum were the most abundant. The seasonal abundances of these ticks and of Amblyomma marmoreum, Rhipicephalus appendiculatus, Rhipicephalus evertsi evertsi and Rhipicephalus zambeziensis were determined. The kudus were also infested with 3 lice and 1 louse fly species, as well as the nymphs of a pentastomid. Sixteen kudus were shot in the Andries Vosloo Kudu Reserve, eastern Cape Province and 9 on an adjacent farm. These animals were infested with 12 tick species. A. hebraeum followed by Rhipicephalus glabroscutatum were the most abundant on kudus in the reserve and R. glabroscutatum followed by Haemaphysalis silacea on the animals on the farm. The seasonal abundances of A. hebraeum, A. marmoreum, H. silacea, R. appendiculatus, R. glabroscutatum and a Rhipicephalus sp. (near R. oculatus) were determined on the kudus in the reserve. The kudus were also infested with 3 lice and 1 louse fly species. Two kudus examined in the Addo Elephant National Park were infested with 6 tick, 1 louse and 1 louse fly species. PMID- 1297958 TI - The effect of veld-burning on the seasonal abundance of free-living ixodid ticks as determined by drag-sampling. AB - A supervised veld-burn in the Sclerocarya caffra/Acacia nigrescens Savanna landscape zone in the south-eastern region of the Kruger National Park was carried out during September 1988. The effect of the fire on the free-living tick population was determined by comparing the numbers of ticks collected by monthly drag-sampling in the burnt zone with those collected in an adjacent unburnt zone over a 2-year period. A total of 13 ixodid tick species were involved. Tick numbers were reduced after the burn but rose again after varying periods of time. The length of these periods depended upon a number of variables. These included tick species, patterns of seasonal abundance, and host preferences. The original reduction in numbers seemed to result in subsequent cyclical population fluctuations and in some instances overcompensation was noted. Veld-burning as a control technique may be effective with tenuously adapted tick species or reduced populations and may be enhanced by the exclusion of major hosts for a critical period after the fire. PMID- 1297959 TI - A new species of Lipoptena (Diptera:Hippoboscidae) from southern Africa. AB - A new species of Lipoptena Nitzsch, 1818 was found on springbok Antidorcas marsupialis Zimmerman, 1780 in the Cape Province and the Orange Free State, South Africa. The flies, for which the name Lipoptena annalizeae is proposed, can be differentiated from the closely related Lipoptena sepiacea Speiser, 1905 on size, palps, chaetotaxy, pulvilli, and the shape of the posterior genital plates of the males. The morphology of the puparium of the new species is also described and compared with that of the puparia of Lipoptena paradoxa Newstead, 1907 and Lipoptena binocula (Speiser, 1908). A revised key to the southern African species and a summary of host records and distributional information is also presented. PMID- 1297960 TI - The louse fly Lipoptena paradoxa Newstead, 1907 (Diptera:Hippoboscidae): description of its adult and puparium and biology in South Africa. AB - Lipoptena paradoxa Newstead, 1907 is re-described using scanning electron microscopy and its puparium is described for the first time. The distribution of the fly is restricted to the eastern half of South Africa, generally at altitudes below 600 m. Its preferred hosts are all browsing antelope namely, bushbuck, nyalas, kudus and common duikers. The largest numbers of flies were present on kudus in the Kruger National Park from July or August to January and large numbers were recovered from these animals' tails from November to January. Considerably more female than male flies were collected. PMID- 1297961 TI - Galenia africana L. poisoning in sheep and goats: hepatic and cardiac changes. AB - Lesions in 4 field cases (3 sheep and 1 goat) of 'waterpens' or water belly, caused by the plant Galenia africana, are described. The clinical pathological and pathological findings in 7 sheep which were drenched with toxic plant material are also reported. Inappetence, ruminal stasis and apathy as well as tachycardia were noticed in some of the sheep towards the end of the dosing period. The most prominent clinical pathological change in the experimental animals was an increase in the activity of gamma-glutamyltransferase which in some animals occurred within days after commencement of dosing. This indicates liver involvement in the early stages of the intoxication, and at this stage no heart abnormalities were detected clinically, clinical pathologically or with cardiac function tests. Decrease in cardiac function were recorded in 2 sheep towards the end of the dosing period. Liver and heart lesions were present in all the animals. In some cases hepatic changes were mild and characterized by dilation of central veins and sinusoids and, less commonly, centrilobular fibrosis. More advanced lesions included centrilobular fibrosis and bridging between neighbouring lobules with adjacent areas of coagulative necrosis, lysis and ballooning degeneration of hepatocytes. Myocardial changes occurred in the free ventricular walls and interventricular septum and comprised hypertrophy of myocytes with consequent degeneration and necrosis and fibrosis. In cases of longer duration myocytes were diffusely atrophic with scattered groups of remaining hypertrophic fibres. The clinical pathological and pathological features suggest that G. africana is primarily hepatotoxic with myocardial involvement occurring only in the terminal stages of the intoxication. PMID- 1297962 TI - An orf-like condition caused by trombiculid mites on sheep in South Africa. AB - Some flocks of sheep in the Amersfoort district of Transvaal Province developed orf-like lesions, commencing between December and April. The causative agent was identified as a new species of mite belonging to the genus Guntheria of the family Trombiculidae. PMID- 1297963 TI - Flow cytometric analysis of T cell response in mice infected with Cowdria ruminantium. AB - A 3-fold increase in the numbers of Lyt-2+ T cells in the circulating blood of mice infected and re-infected with the Welgevonden stock of Cowdria ruminantium, as determined by flow cytometry, is supportive evidence that immunity in heartwater is cell-mediated. The rise in Lyt-2+ cells only after re-infection of the mice is further evidence that the development of immunity in heartwater is dependent on the unhindered and adequate replication of C. ruminantium. PMID- 1297964 TI - [The origin of heteroxeny in Sporozoa]. AB - Hypothesis on the origin of Sporozoa from Spiromonadida ancestors is discussed on the basis of the data on their ultrastructure. The phylum Sporozoa comprises three large distinct groups of organisms as follows: Perkinsemorpha, Gregarinomorpha and Coccidiomorpha. Advanced Coccidiomorpha have not descended directly from Gregarinomorpha. Gregarinomorpha and Coccidiomorpha have common ancestors, Protospiromonadida. Heteroxeny is quite common among Coccidiomorpha. The formation of heteroxeny in Coccidiomorpha proceeded in different ways and at different time in different groups. Cystoisospora, Toxoplasma, Aggregata, Atoxoplasma, Schellackia have primary definitive hosts while Sarcocystis, Karyolysus, Haemogregarina, Hepatozoon, Plasmodium, Haemaproteus, Leucocytozoon, Akiba, Babesiosoma, Theileria, Babesia have primary intermediate hosts. PMID- 1297965 TI - [The morphology and biology of Cercaria unidiverticulata sp. n. (Trematoda: Echinostomatidae)]. PMID- 1297966 TI - [Haplosplanchnus pachysomus (Trematoda: Haplosplanchnidae)--a parasite of Black Sea mullets]. PMID- 1297967 TI - [The morphological variability of a population of Proteocephalus percae (Cestoda: Proteocephalidea) in Lake Rindozero]. AB - The morphology of the cestode Proteocephalus percae, a typical parasite of Perca fluviatilis, from Lake Rindozero has been studied. The variability of 8 age groupings has been revealed and the connection of their morphological parameters with the specificity of host-parasite relationships at different developmental stages of the population has been shown. PMID- 1297968 TI - [The ultrafine structure of the body wall of sexually mature thorny-headed worms Echinorhynchus gadi (Acanthocephala)]. AB - Studies of the fine structure of the adult acanthocephalan Echinorhynchus gadi have given a new information on the structure and organization of the body wall of these parasitic helminths. Their body surface is covered by glycocalyx of mucopolysaccharide nature. Just under it there is the surface membrane which has numerous invaginations forming a network of branching canals from which membrane vesicles are isolating. In their turn these canals pass through "the cytoplasmic canals" of the cortical matrix. Between the surface membrane and cortical matrix there is the base plate. These three structures form the striped layer underlain by the felt layer. It is formed by three layers of fibrous strands (one circular and two longitudinal), which are parallel to the body surface. These strands consist of loosely laid fibrils. The lowest layer is a radial one which occupies 2/3 of the body wall. It consists of the radial strands beginning from the cortical matrix and ending at the basement membrane. Numerous lipid droplets and glycogen granules are formed here. Two types of fibrils with 0.26 and 0.05 diameter have been detected for the first time. The radial layer in the cytoplasm was found to have crystalline structures and polymembrane bodies, numerous nuclei with light karyoplasm and distinct nucleoli. The location of the nuclei is of two types: either in the cytoplasm or in the "lacunae". We have shown that the "lacunae" are specialized sites of the cytoplasm whose boundaries are marked by the fibres of two types. Besides, this type of the acanthocephalan was found to have two "giant lacunae" extending along the body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1297969 TI - [A new species of flea in the genus Ctenophthalmus (Siphonaptera: Hystrichopsyllidae)]. AB - A new species, Ctenophthalmus (Euctenophthalmus) parthicus sp. n., is described from social vole (Microtus socialis Pallas) from four localities of the West Kopetdag Mountains of Turkmenia. The new species is close to C.(E.) secundus Wagner and C.(E.) congener nadimi Farhang-Azad. It differs from males of the other known species by the following characters. The movable process has an infra acetabular process whose length is the same as the height of its supra-acetabular portion. The movable process has the straight front margin, right anterior apical angle. The anterior part of the dorsal margin of the movable process is elevated, the hind part is slightly concave. The posterior apical angle of the movable process is cut. The hind margin of the movable process is convex. The apex of the distal arm of sternum IX is straight, not oblique. The female differs by the following peculiarities. Sternum VII has a well developed dorsal lobe below which there is a smaller rounded lobe and a distinct small ventral process. Unciform sclerotization of tergum VIII (or the place of connection between tergum VIII and its internal lobe) resembles an arc. The front margin of the internal lobe of tergum VIII is not sclerotized. The bursa copulatrix is as long as the dorsal spines of pronotum. PMID- 1297970 TI - [Experimental interspecific hybridization in fleas of the genus Nosopsyllus (Siphonaptera: Ceratophyllidae)]. AB - Experimental interspecific hybridization between males and females of Nosopsyllus fasciatus and N. mokrzeckyi was carried out. Most abundant progeny was obtained after hybridization between N. fasciatus females and N. mokrzeckyi males. Hybrid descendants inherited, in general, the characters of the maternal species and in less number the paternal characters and those of both parents. The fecundity of hybrid progeny of N. fasciatus females and N. mokrzeckyi males in two generations was studied. A conclusion is made concerning close affinity of the species and their relative evolutionary youth. PMID- 1297971 TI - [An analysis of the morphometric traits of the pupae of 3 populations of Testisimulium kondici (Diptera: Simuliidae)]. AB - In the pupae of three populations of Testisimulium kondici (Bar.) the variations of nine quantitative characters are determined. The discrepancies between these populations are analyzed. With the help of statistical indices the specific distinctions of one of the studied populations from two others, which are not essentially different, is established. Earlier (Kachvorian, 1989; Kachvorian and Tonoian, 1990) karyological and phenotypical differences between the larvae of these populations were found. Considering that the isolated population develops under anthropogenic influence a link between the above discrepancies and this influence is assumed to exist. PMID- 1297972 TI - [The absolute number of the stable fly (Stomoxys calcitrans) in the buildings of dairy farms]. AB - In order to estimate the absolute number of Stomoxys calcitrans subpopulation in housings of a dairy farm the capture-mark-recapture method has been used. It has been established that the absolute number of S. calcitrans subpopulation can be as high as 100,000 specimens per a farmyard. The possibilities of using indices of the relative number of flies (caught on fly-paper) for estimation of the absolute number of these insects in the housings of farms have been found out. PMID- 1297973 TI - [The finding of the eggs of the nematode Eustrongylides excisus in true sturgeons of the Caspian Sea]. AB - The finding of eggs of the nematode Eustrongylides excisus has been reported from true sturgeons of the Caspian Sea. The nematode is in the capsule with an opening into the cavity of the alimentary canal. In addition to birds, true sturgeons are expected to be under certain conditions definitive hosts of this nematode. PMID- 1297975 TI - Lateral masking as a determinant of global dominance. AB - The term compound letter refers to a large (global) letter made up of small (local) letters. Reaction time to identify local letters is longer when local and global letters are different than when they are the same (the global dominance effect). The possible contribution of lateral masking to this effect was investigated. Lateral masking denotes reduced probability of identifying a stimulus when it is closely surrounded by other stimuli (as is the case for the local items in a compound stimulus). Three experiments were conducted in which the dependent measure was percentage of correct responses, rather than reaction time. In experiment 1 compound letters were used; accuracy of performance yielded evidence of global dominance such as obtained with reaction time measures. In experiments 2 and 3 the strength of lateral masking in geometrical forms was varied by varying the density of their component items. In agreement with earlier suggestions based on indirect evidence, the results directly implicated lateral masking as an important determinant of global dominance. However, lateral masking could not account fully for the experimental outcome. Factors beyond lateral masking, such as global precedence in the processing sequence or inhibitory interactions among low and high spatial-frequency components of the compound images are required in order to provide a comprehensive account of global dominance effects. PMID- 1297974 TI - [The cultivation of Blastocystis (Rhizopoda: Lobosea) from hens and ducks]. AB - The method of cultivation of Blastocystis galli from hens and Blastocystis sp. from ducks was worked out. Blastocystis grow on nutrient medium at pH 7.0 to 7.2 in a wide range of temperatures from 30 to 45 C. Optimum temperatures for cultivation are 41 to 42 C. The growth of cultures was obtained on biphase egg medium. Solid phase of the medium presents coagulated contents of the hen's egg. Liquid phase can be made of Henk's solution with the addition of 30% of fresh or lyophilizinic hen serum or horse serum. Henk's solution can be replaced by medium 199 (we observed the growth of culture on medium 199 without addition of blood serum). In all variants of medium we added antibiotics on a per--1 ml of medium basis: ampicillini--4 thousand units, streptomycini--1 thousand units. After 2 to 3 passages antibiotics can be excluded from the medium. Optimum medium is that with the addition of 30% of fresh hen serum. Passages go well at the transfer of 15-20% culture after 72 to 96 hours. The size of cultural stages varied within the limits of 2.5-56.2 x 2.5-56.2 microns and 2.5-110 x 2.5-110 microns for Blastocystis sp. and B. galli, respectively, the number of nuclei in one individual varied from 1 to 64, seldom over 100. PMID- 1297976 TI - Colour inputs to random-dot stereopsis. AB - Recently it has been claimed by Livingstone and Hubel that, of three anatomically and functionally distinct visual channels (the magnocellular, parvocellular interblob, and blob channels), only the magnocellular channel is involved in the processing of stereoscopic depth. Since the magnocellular system shows little overt colour opponency, the reported loss of the ability to resolve random-dot stereograms defined only by colour contrast seems consistent with this view. However, Julesz observed that reversed-contrast stereograms could be fused if correlated colour information was added. In the present study, 'noise' (non corresponding) pixels were injected into random-dot stereograms in order to increase fusion time. All six subjects tested were able to achieve stereopsis in less than three minutes when there was only correspondence in colour and not in luminance, and three when luminance contrast was completely reversed. This ability depends on information about the direction of colour contrast, not just the presence of chromatic borders. When luminance and chromatic contrast are defined in terms of signal-to-noise ratios at the photoreceptor mosaic, chromatic information plays at least as important a role in stereopsis as does luminance information, suggesting that the magnocellular channel is not uniquely involved. PMID- 1297977 TI - Resolving ambiguities in orientation, motion, and depth domains. AB - Three different perceptual systems--orientation, motion, and depth--can recover a global perceptual organization from spatially correlated random multielement patterns. In all three cases the global structure composed of random elements is evaluated by mechanisms performing measurements in the energy domain within appropriately defined local space-time areas. The selective increase in energy of one fraction of the elements may dramatically change the whole perceptual organization of the stimulus. In specially devised patterns one and the same element can belong to two or more separate perceptual organizations, the perceptual salience of one of which can be reinforced by a luminance increment of the elements comprising it. If a stimulus provides two different perceptual organizations to which each element could potentially belong, one of four possible solutions of the existing ambiguity will occur: suppression, rivalry, mixture, or parity. Two superimposed global orientation patterns either suppress or dominate over each other but cannot be seen simultaneously or in a mixed form. Characteristic of the depth system is that it allows multiple binocular matchings and parity of possible perceptual solutions. Finally, if a stimulus provides two or more paths along which each element may appear to move, the perceived global motion direction is determined by a mixture of directions of these competing motion paths. Dissimilarities in these ways of resolving ambiguities may be based on different principles defining regularity and coherence of an object in the orientation, motion, and depth domains. PMID- 1297978 TI - Depth perception of interfering periodic patterns: a possible contribution to disorientation on escalators. AB - Incongruous and illusory depth cues, arising from 'interference patterns' produced by overlapping linear grids at the edges of escalator treads, may contribute to the disorientation experienced by some escalator users, which in turn may contribute to the causes of some of the many escalator accidents which occur. The apparent depth of the interference pattern from the viewer is analysed in terms of the cues deriving from size and viewer motion. Both of these cues support the depth of the target being infinite. Preliminary observations are reported which confirm this analysis. Remedies for the problem are suggested. The possible contribution of this illusion to disorientation on escalators, due to misjudgment of depth, is compared with another recently reported factor which is due to stereoscopic miscorrespondence of periodic targets. PMID- 1297980 TI - Visual search: detection, identification, and localization. AB - In two studies, observers searched for a single oblique target in a field of vertical distractors. In one experiment, target detection and identification (left versus right tilt) were compared. In another experiment, detection and localization were compared for the left versus the right half of the display. Performance on all three tasks was virtually identical: if a target could be detected, it could also be identified and localized. A review of previous studies generally supports the conclusion that performance on the three tasks is similar. This argues against current search theories, which rest heavily on data showing differences in identification and localization. PMID- 1297979 TI - Contrast sensitivity during horizontal visual pursuit: dynamic sensitivity functions. AB - The contrast sensitivity functions of college students for grating targets presented at angular velocities of 0, 30, 60, and 90 deg s-1 were determined for target durations of 200 and 600 ms. The most pronounced effects of target movement were evident at the mid to high spatial frequencies in which sensitivity was markedly reduced as velocity increased. These adverse effects were greatest in the 200 ms condition, in which performance was largely limited to the saccadic eye movement system. In the 600 ms condition, in which both saccadic and smooth pursuit eye movements were possible, contrast sensitivity for the low-frequency target actually improved significantly for the 30 and 60 deg s-1 targets, whereas only adverse effects of target motion were found for targets of mid and high spatial frequencies. The results are discussed in terms of the limitations of traditional visual assessment procedures and the practical and theoretical benefits of conceptualizing the joint effects of target composition and target movement. PMID- 1297981 TI - Grouping based on phenomenal similarity of achromatic color. AB - It is widely acknowledged that a precondition for the perception of the world of objects and events is an early process of organization, and it has generally been assumed that such organization is based on the Gestalt laws of grouping. However, the stage at which such grouping occurs, whether early or late, is an empirical question. It is demonstrated in two experiments that grouping by similarity of neutral color is based not on similarity of absolute luminance at the level of the proximal stimulus, but on phenomenal similarity of lightness resulting from the achievement of lightness constancy. An alternative explanation of such grouping based on the equivalence of luminance ratios between elements and background is ruled out by appropriate control conditions. PMID- 1297982 TI - Visible persistence is reduced by fixed-trajectory motion but not by random motion. AB - Despite the sluggish temporal response of the human visual system, moving objects appear clear and without blur, which suggests that visible persistence is reduced when objects move. It has been argued that spatiotemporal proximity alone can account for this modulation of visible persistence and that activation of a motion mechanism per se is not necessary. Experiments are reported which demonstrate that there is a motion-specific influence on visible persistence. Specifically, points moving in constant directions, or fixed trajectories, show less persistence than points moving with the same spatial and temporal displacements but taking random walks, randomly changing direction each frame. Subjects estimated the number of points present in the display for these two types of motion conditions. Under conditions chosen to produce 'good' apparent motion, ie small temporal and spatial increments, the apparent number of points for the fixed-trajectory condition was significantly lower than the apparent number in the random-walk condition. The traditional explanation of the suppression of persistence based on the spatiotemporal proximity of objects cannot account for these results. The enhanced suppression of persistence observed for a target moving in a consistent direction depends upon the activation of a directionally tuned motion mechanism extended over space and time. PMID- 1297983 TI - Spatial orientation in weightless environments. AB - Illusions of body inversion and of vehicle inversion can be evoked by exposure to weightlessness in the microgravity conditions of orbital and parabolic flight. Such illusions can involve all possible combinations of self-inversion and vehicle inversion. In the absence of any patterns of external stimulation, individuals may lose all sense of body orientation to their surroundings while retaining a sense of their overall body configuration and cognitive awareness of their actual position. Touch and pressure cues provide a perceptual 'down' in the absence of visual input. When vision is allowed, apparent orientation is influenced by a variety of factors including the direction of gaze, the architectural layout of the vehicle, and sight of the body. The relative importance of the various factors affecting orientation changes with repeated exposure. The virtual absence of sensations of falling during exposure to free fall emphasizes the role of cognitive factors in experienced orientation. PMID- 1297984 TI - Mobility of normal observers under conditions of reduced visual input. AB - The importance in mobility performance of the rate of presentation of visual information, binocular versus monocular vision, the use of multiple rather than single reference points, and local motion parallax was investigated in two experiments. In each experiment ten subjects walked a triangular mobility course in a totally darkened room; the only visible targets were light emitting diodes (LEDs), mounted on poles, at the apices of the triangle. The LEDs were mounted so that one or two could be used in a trial; if two were used the distance between them was varied horizontally (in experiment 1) and vertically (in experiment 2). The subjects walked around the course under a range of conditions, including two 'optimal trials' in full light. The LEDs were flashed for 1 ms at frequencies of 0.5, 1 and 5 Hz in experiment 1 and at 1 and 5 Hz in experiment 2. Mobility was measured with the use of an ultrasonic locator system which measured the subject's position on the course 10 times per second. The mean velocity of the subject in traversing the course was significantly reduced when the flash rate was slower, when the subject had one eye occluded, or when there was only one LED on the pole; when the spacing between the LEDs was varied, either vertically or horizontally performance was unaffected. These results imply that the frequency of updating of visual information is important in determining mobility performance, as are binocular cues, but that local motion parallax is not important. The number of LEDs on each pole had a significant effect on mobility performance an 'object' (two lights) gave more information than a point reference. PMID- 1297985 TI - Calcium ion homeostasis in smooth muscle. AB - Ca2+ plays an important role in the regulation of smooth-muscle contraction. In this review, we will focus on the various Ca(2+)-transport processes that contribute to the cytosolic Ca2+ concentration. Mainly the functional aspects will be covered. The smooth-muscle inositol 1,4,5-trisphosphate receptor and ryanodine receptor will be extensively discussed. Smooth-muscle contraction also depends on extracellular Ca2+ and both voltage- and Ca(2+)-release-activated plasma-membrane Ca2+ channels will be reviewed. We will finally discuss some functional properties of the Ca2+ pumps that remove Ca2+ from the cytoplasm and of the Ca2+ regulation of the nucleus. PMID- 1297986 TI - Strategies for identification of peptide growth factors. AB - Numerous peptides are known that have specific functions as growth factors in different tissues. These bioactive peptides are characterized by their ability to bind to high-affinity receptors, by their classification into superfamilies that share homology and function and by their synthesis as large precursor molecules that are processed to active forms. In some cases the precursors themselves also have biological activity. Modulation of growth factor activity at the level of the receptor or effector molecules has great therapeutic potential. This article will outline some of the strategies that have been successful in detecting and identifying growth factors and demonstrating their biological activity. PMID- 1297987 TI - Laminin in neural development. AB - This short and selective review of the role of laminin in neural development discusses emerging concepts about the way that elements of the extracellular matrix control the differentiation of embryonic neurons. New laminin isoforms have recently been discovered, discoveries which now reveal the very great heterology of basement membranes in different regions of the nervous system, at different stages of development. The problems of identifying true, neuronal specific laminin receptors are also discussed, particularly with reference to neuronal pathway formation. PMID- 1297988 TI - [Studies of neurophysiological reactivity and level of activation of the central nervous system in endogenous depression and circulatory system disturbances]. AB - The aim of the study was to assess the neurophysiological factors of simple and complex reactivity of central nervous system in a group of 30 patients treated with endogenous depression and showing circulatory system disturbances, and in a group of 30 patients showing no such somatic problems. The findings showed that the simple and complex reactivity testing can be considered an important and sensitive indicator of the endogenous depression intensity, characteristic of additional circulatory system disturbances and "organic" basis of depression. Any improvement in the circulatory system disturbances and anti-atherosclerotic effect in elderly people should be taken into account. PMID- 1297989 TI - [Psychopathologic picture of patients displaying resignation reactions during repeated dialysis treatment]. AB - A group of 64 patients dialyzed because of a chronic insufficiency of kidneys was examined. Among 57.8% of patients various resignation reactions were noticed. In most cases these reactions were accompanied by depressive syndrome. The occurrence of the syndrome had some influence on the length of the patients' lives. PMID- 1297990 TI - [Psychiatric aspects of repeated dialysis treatment]. PMID- 1297992 TI - [Loneliness]. PMID- 1297993 TI - [Autism in children]. PMID- 1297991 TI - [Adaptation of patients with chronic kidney insufficiency to repeat dialysis treatment]. PMID- 1297994 TI - [The ideal of mental health in Plato's model of society (on the basis of 10 polytheistic volumes)]. PMID- 1297995 TI - [Psychopathologic analysis of Sylvia Plath's personality on the basis of letters to her mother]. PMID- 1297996 TI - [Some factors influencing psychiatrists' and psychologists' opinions about dangerous behavior]. PMID- 1297997 TI - [Smoking cigarettes and psychiatric disorders]. PMID- 1297998 TI - [Possibilities of reducing psychiatric hospitalization from systemic and social perspectives in psychiatry]. PMID- 1297999 TI - [Further development of a computer program for supporting psychiatric diagnosis and choice of therapy]. AB - The algorithm grouping the patients into natural subsets, according to their psychopathological features or results of laboratory examinations, was extended by a software enabling the allowance of a new patient to the nearest subset taking into account any features describing the representative set. Apart from that the system was extended by a software of multi-criterion assessment of drug usability in empirical subsets of patients. It was found out that the developed information system makes it possible to assess such relations between the features of the examined phenomenon that would not be noticeable without using the system. PMID- 1298000 TI - [Psychopathologic picture of depression and the conduct of some hormone tests and the therapeutic response to thymoleptics]. AB - Psychopathological picture of depression and the conduct of some hormone tests vs the therapeutic response to thymoleptics were examined. On the grounds of some diagnostic criteria, 84 patients with affective psychosis were divided into three diagnostic groups: unipolar (DJ, n = 54) and bipolar (DD, n = 20) endogenous depressions and non-endogenous depression (DN, n = 10). The control group (GK, n = 25) consisted of mentally healthy people. Hormone tests TRH and ITT were performed before and after the treatment. The hormones: TSH, T4, T3, PRL, GH, and CORT were marked by RIA methods. The findings of the examination, after being statistically described and thoroughly discussed, show that they could be useful in differential diagnosis of affective illnesses and in prognosis of therapeutic response. PMID- 1298001 TI - [Salivation test in patients with affective disorders treated with amitriptyline, mianserin and electroconvulsive therapy]. AB - The aim of this work was assessment of the peripheral anticholinergic effects by use of a salivary test in patients with depression on the background of affective disease, treated over four weeks in a psychiatric department by one of three methods: amitriptyline, mianserin or nondominant unilateral electroconvulsive therapy (NDULECT). There were 22 patients treated with amitriptyline, 26 mianserin and 20 by NDULECT. The degree of depression was assessed by Hamilton's scale of depression and was similar in the groups of patients compared. Also the amount of saliva excreted was similar in the material examined before treatment. Among the methods of treatment the most severe inhibition of salivation was noted in the group treated with amitriptyline, the least--after NDULECT. Mianserin reduced salivation to a small degree--taking up a middle position in the comparison of methods of treatment. Practically speaking there is a conclusion: in patients whose somatic condition contraindicates, during treatment of endogenous depression, unwanted symptoms occurring after inhibition of the cholinergic receptor, the most acceptable of the three methods would be the use of mianserin or NDULECT. PMID- 1298002 TI - [Biochemical evaluation of atherosclerotic changes in the course of depressive syndromes in patients with cardiovascular disturbances]. AB - The paper analyses correlation between depressive syndromes and lipid metabolism and circulatory system disturbances. Two groups of patients with depression were compared. The first of them consisted of patients with an increased risk of atherosclerosis, in the other group there were patients with normal risk of atherosclerosis. It was found out that the most frequent parameter of lipid metabolism disturbances is cholesterol HDL fraction. Lipid metabolism disturbances in depression are larger in patients suffering from circulatory system disorders. The authors recommended to combine the treatment of depression with applying medicines counteracting lipid metabolism disturbances in patients having greater risk of atherosclerosis. PMID- 1298003 TI - [Weight gain during antidepressant therapy]. AB - Changes of weight were assessed within a population of 329 patients with major depressive disorders and neurotic states, treated with amitriptyline, doxepin, insidone and imipramine. It has been found that the most important increase of body weight occurred in the groups of patients treated with amitriptyline and doxepin. In the group of insidone the increase of weight was not so high as in the previous groups. The patients treated with imipramine lost weight in the first three weeks of the treatment. No relationship between the increase of body weight and diagnosis, doses of antidepressants, age, sex and education has been observed. PMID- 1298004 TI - [Quantitative evaluation of motor activity of children with hyperkinetic syndrome]. AB - Quantitative assessment of children's motor activity is necessary to objective classification of children according to their motor activity. The authors of the study made a quantitative assessment of motor activity of 55 boys in the age from 8-12, with normal IQ, using motor-scopic-motor-metric method. Global motor activity was assessed together with the activity of the head, trunk, and limbs, in such testing situations as sitting, standing, lying, and reading. It was found out that quiet children make 6.4 movements per minute, and hyperkinetic children make 21.4 movements per minute. Assessment of motor activity of upper limbs (arms, hands, fingers) is a sufficient factor to assess motor activity of children and verify their hyperkinetic syndrome. In such conditions 3.1 movements per minute is a borderline for quiet children and 6.4 movements per minute for hyperkinetic children. It was found out that the growing-up process leads to lessening of motor activity, especially in hyperexcitable children. PMID- 1298005 TI - [Usefulness of Widlocher scale in assessment of psychomotor activity disorders in endogenous depression]. AB - A group of 50 patients with a diagnosis of affective disease was examined. Dependence between the intensification of depression psychomotor activity measured according to Widlocher scale was established. Neurophysiological factors (such as thinking productivity, letter drafting, tapping test, simple reaction time) correlated with the intensification of psychomotor activation disorders. PMID- 1298006 TI - [Depressive disorders with psychomotor activity in patients with alcohol dependence syndrome]. AB - In a group of 85 men with alcohol dependence syndrome occurrence of depressive symptoms was examined and the intensification of psychomotor activation disorders was assessed. 60% of patients showed symptoms of depression during alcohol intoxication. Relationship between the intensification of depressive symptoms and psychomotor activity disorders was testified. PMID- 1298007 TI - [Depressive syndromes in patients dependent on alcohol with regard to mental disorders in the family]. AB - We looked for the present and past history of functional disorders, especially mood disorders among 215 inpatients with diagnosis of alcohol dependence using Schedule for Affective Disorders and Schizophrenia--Life-time Version (SADS-L). This same was determined in their first degree relatives using Family History- Research Diagnostic Criteria (FH--RDC). The incidence of mood disorders among probands was rather low--9.8% (bipolar--0.9%, recurrent depression--2.8%, minor depression--6.0%), the occurrence of other functional disorders was much more rare: 2 patients--panic disorder, 2--general anxiety disorders. Among first degree relatives only two had history of depression. The incidence of alcoholism was rather high, especially in men. PMID- 1298008 TI - [Personality features of spouses married to depressive partners]. AB - 30 married couples in which one spouse was hospitalized with a diagnosis of depressive syndrome testified by psychological tests (ACL, MPI, STAI, Self perception Sheet, Zung SRDS) were examined. Taking into account the literature concerned with the role of improperly functioning couples, the author of the study tried to determine the influence of the healthy spouse's personal character and his/her patterns of behavior on their ill partners. It was found out that the mechanism of the relationship is different depending whether the patient is a wife or a husband. The healthy spouse's mental balance had a positive influence on the patients, independently of sex. A higher level of symptoms and depressive behavior of men was connected with good functioning and adaptation of their wives. On the other hand, the women were having more depressive symptoms if their husbands were submissive and emotionally unstable. It might be connected with the ill spouse's feeling of failing as a wife or husband. The findings may be important for the family therapy of depressed people. PMID- 1298009 TI - [Siblings of children with a serious mental handicap (psychologic-psychiatric evaluation)]. AB - A group of 150 siblings of children with serious mental handicap was examined. It was established, that frequency of occurrence of psychiatric disorders in this group was no more often than in general population. PMID- 1298011 TI - [Some intellectual factors and the clinical picture during the first hospitalization of schizophrenic patients]. AB - A group of 62 patients treated with schizophrenia for the first time was examined. Connection between the IQ, the type or interests, Bleulers' primary symptoms and Schneider's criteria was analyzed. A number of dependence factors were discovered, what allowed to draw conclusions about the role of intelligence and interest in patients' first manifestation of schizophrenia. PMID- 1298010 TI - [Influence of family factors in the first occurrence of psychiatric hospitalization of patients suffering from schizophrenia]. AB - The paper is an empirical verification of a thesis according to which inter family factors decide, to a large extent, about the psychiatric hospitalization of patients suffering from schizophrenia. On examining a population of 48 patients hospitalized for the first time because of schizophrenia and their families, it turned out that the family slowness in reacting to psychosis (defining the changes in the patient's behavior as morbid, and looking for a medical assistance occurred too late) is connected with a particular constellation of the family factors "Sluggish" families are mainly those with a lack of feelings, or families "fighting by the child". Initiative of seeking the help was triggered by the patient's behaviour that, from sociological point of view, could be characterized as rebellion and alienation. PMID- 1298012 TI - [Social functioning of patients with schizophrenia who are employed and unemployed]. AB - A group of 130 patients having been treated with schizophrenia for at least 5 years was examined. The patients were trying to get a job after at least one year leave. All subjects were examined twice: at the time of looking for a job and two years later. Adaptability level and the course of employment during the period of two years were assessed. It was found out that 40% of patients continued work after two years but majority of those were working in firm for disabled people. Professional work positively influenced the patients' self-dependence. It was proposed to motivate all patients treated with schizophrenia to start professional work. PMID- 1298013 TI - [Clinical state of patients with schizophrenia who are employed and unemployed]. AB - A group of 130 patients having been treated with schizophrenia for at least 5 years was examined. The patients were trying to get a job after at least one year leave. All subjects were examined twice: at the time of looking for a job and two years later. Mental state, the course of the disease, and the employment during the period of two years were assessed. It was found out that 40% of patients continued work after two years but majority of those were working in firm for disabled people. Professional work positively influenced the patients' mental state, namely the psychopathological symptoms occurred less often in patients working professionally. No differences were spotted in the number and the general length of hospitalization during two years of catamnesis between the working and unemployed groups. It was proposed to motivate all patients treated with schizophrenia to start professional work. PMID- 1298014 TI - [Utilization by Escherichia coli and Pseudomonas fluorescens of a siderophore from Pseudomonas fluorescens strain PAB]. AB - Pseudomonas fluorescens PAB strain produced pyoverdine in a synthetic medium. Pigment was purified by solvent extraction and ion exchange, and sterilized and used as siderophore for E. coli, P. fluorescens, ATCC 13.525, ATCC 17.400, W and PAB strains. Bacteria were grown in iron-free medium and medium with iron. Free- pyoverdine and pyoverdine bound to Fe+3 were added in different concentrations. P. fluorescens PAB siderophore did not stimulate E. coli growth while it was selective for other P. fluorescens strains. Paper disks impregnated with pyoverdine did not inhibit E. coli growth. PMID- 1298015 TI - Characterization of Bacillus larvae White, the causative agent of American foulbrood of honey-bees. First record of its occurrence in Argentina. AB - American foulbrood caused by Bacillus larvae White is recorded for the first time on brood combs of Argentinian hives. The identification of the causative agent was based on disease symptomatology, morphological characters, pathogenicity tests and physiological and biochemical reactions. Studies by scanning electron microscopy showed the occurrence of large flagellar bundles of Bacillus larvae strains growing in biphasic BL medium. An electron microscope survey of the surface configuration of bacterial spores was also made. PMID- 1298016 TI - [Prevalence of Staphylococcus aureus isolated from subclinical bovine mastitis in dairies of the city of San Luis]. AB - In order to detect subclinical mastitis by means of California Mastitis Test and recounting of somatic cells, 163 cows from the dairies of San Luis city, Argentina, were examined. Seventy six individuals (46.6%) exhibited an inflammatory response ranging > or = 2+ grade and a cellular recounting value of > or = 5 x 10(5), data compatible with those of subclinical mastitis. Staphylococcus aureus was isolated from 39 (51.3%) cultures as estimated by the sum of the two last values listed in Table 1. Organisms were isolated by plating on brain heart infusion agar with 5% of sheep blood and on Baird-Parker media. One hundred and three S. aureus isolates recovered from 51 of 63 cows were characterized by coagulase activity by the tube method using human and bovine plasma; clumping factor; glucose and mannitol fermentation; thermonuclease (TNase), pigment, gelatinase, fibrinolysin, acetoin, hemolysin production; egg yolk, tellurite and catalase reaction and crystal violet types. All isolates were susceptible to cephalothin, clindamycin, methicillin, gentamycin and vancomycin; 94.1% were susceptible to chloramphenicol and 53.8% to G penicillin. Sixty three isolates (61.1%) were classified according to Hajek and Marsalek scheme as biotype C (bovine and ovine ecovar), 33 isolates (32.0%) were classified as biotype B (swine and poultry ecovar); 1 isolated (0.9%) as intermediate between B and D; 5 isolates (4.8%) as biotype A (human ecovar) and 1 isolated (0.9%) as biotype D (ecovar silvestres spp) (Table 2). Production of enterotoxins A to E and toxic shock syndrome toxin-1 (TSST-1) was determined by the optimal susceptibility plate method on 27 isolates (26.2%) which were coagulase 3+ to 4+ and TNase highly positive. None of them produced enterotoxins including TSST-1. The subclinical mastitis data and the prevalence of S. aureus coincide with those of other authors, both from Argentina and from other countries. PMID- 1298017 TI - Trypanosoma cruzi: incorporation of macromolecule precursors during the morphogenic process. AB - During the morphogenic process from epimastigote to metacyclic trypomastigote stage changes at molecular levels are produced. In the present work the incorporation of macromolecule precursors L [3H]-leucine, [3H]-thymidine and [3H] uridine was used to monitor the differences between parasites growing with and without specific stimulation for morphogenesis (SEpi and NEpi, respectively). The peak of maximum [3H]-uridine incorporation was earlier in the SEpi than in NEpi (3 vs 4 days, respectively) reaching 129% higher values. Even at day 2, SEpi already showed values of [3H]-uridine incorporation slightly higher (29%) than the maximum reached by NEpi. One the other hand the peak of L-[3H]-leucine incorporation was 48 h delayed comparing SEpi vs NEpi with quantitatively similar patterns, while no differences were registered for [3H]-thymidine incorporation. Therefore the [3H]-uridine incorporation may constitute an earlier marker of morphogenesis since the process was optically detected starting day at 6. PMID- 1298018 TI - [Production of xanthan gum in immobilized cultures of Xanthomonas campestris]. AB - The efficiency of xanthan production through surface processes was evaluated. The best porous material was selected first. Thereafter, a comparative study was performed using submerged agitated process vs other without agitation but containing the selected porous material. The culture medium used was white potatoes infusion, buffered with K2HPO4 and supplemented with glucose in diverse concentrations. Besides, to evaluate a different type of surface process, three vegetables were valued: Ipomaea batatus, Solanum tuberosum and Daucus carota, with an without glucose supplement. Larger xanthan production was achieved with immobilization of X. campestris vs the conventional method, when the liquid culture medium was used. The highest yield was obtained when the white potatoes infusion was supplemented with glucose 2.5%, yielding a conversion of this saccharide to xanthan up to 58%. When X. campestris was cultured on fragmented vegetables, the highest xanthan gum yield (5.6g) was obtained with Solanum tuberosum supplemented with glucose. This yield indicators that X. campestris used the glucose added as well as the constitutive polysaccharide of this vegetable. PMID- 1298019 TI - [Molecular analysis of the principal neutralization epitope (V3 loop) of human immunodeficiency virus type 1 in Argentina]. AB - The main goal of the present paper was to analyze the molecular diversity of the principal neutralizing domain (V3 loop) of the HIV 1 gp120 in samples from patients of Argentina. The study was carried out on a total of 30 HIV 1 positive blood samples, obtained during 1991-1992, belonging to 15 intravenous drug users (group A), 5 homosexual men (group B), 8 children born to HIV 1 positive mothers (group C) and 2 AIDS patients (group D). By using extracted DNA from peripheral blood lymphocytes and from infected cells of the viral isolates in the case of the 2 AIDS patients, the V3 loop region was amplified by means of polymerase chain reaction. Direct sequencing by Sanger methodology was then performed on DNA fragments and nucleotide sequences obtained were translated into the correspondent amino acids. Consensus sequences for each group and a general consensus sequence were established (Table 1). Its alignment with V3 loop amino acid sequences of the major HIV 1 strains isolated worldwide is showed in table 2. Homology analysis between each sequence of the study population and sequence of different HIV 1 isolates showed that most of these samples share high homology with SF2 and BH10 strains. In contrast a low homology was found with JH3 and MN isolated (table 3). The presence of highly conserved amino acid residues as substitutions and insertions was determined in the Argentinian V3 loop sequences giving them a local pattern. The present paper is of great importance for our country, considering that the V3 loop is the main neutralizing domain becoming a major target in the development of HIV 1 vaccine. To our knowledge, this is the first report on the sequencing of the principal neutralizing domain of the Human Immunodeficiency Virus type 1 in Latin America. PMID- 1298020 TI - [Epidemiology of the main respiratory viruses in small ruminants in Mali]. AB - From 1986 to 1988 a sero-epidemiological survey was carried out in Mali by ILCA to identify the small ruminant main respiratory viruses. The results of this investigation shows an endemic condition. Regardless of the virus species involved, neutralizing antibodies were detected in adults as well as in young stocks. New researches are necessary to set forth a consistent and effective policy of prophylaxis or treatment according to the case concerned. PMID- 1298021 TI - Detection of adenovirus precipitating antibodies in the sera of Polo horses in Nigeria. AB - Serum samples obtained from 107 Polo horses showing clinical signs of viral respiratory disease were tested for precipitating antibodies to adenovirus by agar gel precipitation test and counter-immunoelectrophoresis method. The results obtained demonstrate serological evidence of adenovirus infection in Polo horses in Nigeria. The counter-immunoelectrophoresis method was observed to be about 3 times more sensitive than the agar gel precipitation test with 19.3 vs 64.5%. It could thus be used to screen a large number of serum samples within a short period. PMID- 1298022 TI - Genital lesions and histopathology of male guinea-pigs infected with trypanosomes. AB - Sixty adult male guinea-pigs were used to study the effect of Trypanosoma brucei brucei and Trypanosoma congolense infections on genitalia, testicles and reproductive capacity. Both infections showed acute to chronic courses. T. b. brucei appeared more virulent than T. congolense. In both cases the infection periods significantly (P < 0.01) influenced resultant decrease in body and gonadal weight, testicular mass index and extent of lesion formation. Histopathological lesions included mononuclear infiltration, distortion of seminiferous tubules and degeneration of germ cells. Both trypanosomes impaired reproductive capacity through impaired hormone biosynthesis, sperm production and reserves. Use of guinea-pigs as a laboratory model for the study of trypanosomosis in domestic animals is discussed. PMID- 1298023 TI - [Determination of the protease activity in a Cuban strain of Babesia bovis]. AB - The attenuation of a Babesia bovis strain depends on its protease content. The present work evaluates this parameter on a virulent strain, before and after attenuation by quick passages on splenectomized calves. The protease activity at different pH values was determined in protein fractions from the blood of calves. The enzymatic test showed marked differences between the protease content of both substrains. PMID- 1298024 TI - [Attempt to attract Amblyomma variegatum (Acarina:Ixodina) on cattle previously treated with aggregation-fixation pheromones and a pyrethrinoid acaricide]. AB - The application of synthetic pheromonal aggregation-attachment compounds or male tick extracts on certain sites of the body of bull calves reared on infested pastures did not induce any attraction of free adults on these sites. Previously attached males were more attractive than synthetic pheromones or natural extracts. Very small amounts of flumethrin poured directly on testicles or on the dewalp induced a large decrease in the infestation of these sites. PMID- 1298025 TI - Ivomec, a treatment against rabbit mange. AB - The trial with Ivomec as a treatment against sarcoptic mange in rabbits gave very encouraging results. There was 100% clinical recovery in 31 rabbits that were treated with no cases of reinfestation. Even though there was no significant difference (P > 0.05) in weight gain between the treated and untreated groups, the efficacy of Ivomec was visually appreciated. Pruritus ceased one week post treatment while total hair regrowth occurred after 6 weeks. PMID- 1298026 TI - [Current status of bovine haemoparasitic diseases in Martinique (French West Indies)]. AB - A serological survey using indirect immunofluorescence (IFAT) for bovine babesiosis (Babesia bovis and B. bigemina) and card test for anaplasmosis, indicates that these haemoparasites are widespread in Martinique. The high prevalences (62% for B. bovis, 52% for B. bigemina and 43% for Anaplasma marginale) lead to the hypothesis of an unstable epizootic situation for these three haemoparasitic diseases. However, the number of smears examined was too low to evaluate their clinical incidence. Both the American and Cuban card tests gave similar results in the detection of antibodies to A. marginale. Theileria mutans is described for the first time in Martinique. Trypanosomosis (Trypanosoma vivax) has disappeared from Martinique, on clinical and serological evidence. PMID- 1298028 TI - DNA fingerprinting of Chlamydia trachomatis by use of ribosomal RNA, oligonucleotide and randomly cloned DNA probes. AB - DNA fingerprinting of 15 reference strains and 24 clinical isolates of Chlamydia trachomatis, 2 strains of C. psittaci and one strain of C. pneumoniae was studied by use of universal 16 + 23S RNA from Escherichia coli, 16S rDNA-directed oligonucleotide and randomly cloned chlamydial DNA probes. The rRNA-gene restriction patterns (ribotypes) enabled the differentiation of chlamydial species. Following DNA cleavage by restriction endonuclease PvuII, lymphogranuloma venereum and trachoma biovars of C. trachomatis could be differentiated. An oligonucleotide, designed to hybridize the C. trachomatis 16S rDNA, also allowed for both species-specific identification and biovar typing of C. trachomatis human strains. Molecular typing system using 3 lambda clones containing C. trachomatis serotype E random DNA inserts, combined to ribotyping, revealed 12 groups of variable banding patterns within C. trachomatis, and could provide an alternative epidemiological tool. PMID- 1298027 TI - Characterization of high molecular weights of complexes and polymers of cytoplasmic proteins in Escherichia coli. AB - To search for filamentous polymers of cytoplasmic proteins of Escherichia coli, high molecular weights (> 670 kDa) of protein complexes of cell extracts were fractionated by gel filtration and ion-exchange column chromatography. Proteins of 100, 77 and 52 kDa were co-purified. The 100- and 52-kDa proteins were identified to be pyruvate dehydrogenase and lipoamide dehydrogenase, respectively, by determining the N-terminal amino acid sequences. Experimental results indicate that the 77-kDa protein is identical to dihydrolipoamide acyltransferase. The 100-kDa protein was found to be identical to the 100-kDa protein described by Tomioka (1991), and was related to the formation of filaments and sheets in the presence of 100 mM KCl. However, neither long filaments nor sheets were observed in our sample containing these enzymes, which was not consistent with Tomioka's conclusion. Another 100-kDa protein which forms spirosome-like particles was purified and identified to be alcohol dehydrogenase based on the N-terminal sequence. PMID- 1298029 TI - Pyrazinamidase activity in Enterobacteriaceae. AB - Pyrazinamidase activity was tested in 1,033 strains of 15 different genera of Enterobacteriaceae. The test was performed by a simple method which reveals the production of pyrazionic acid by a heavy bacterial suspension in 0.2 ml of a 0.5% pyrazinecarboxamide solution in Tris-maleate (0.2 M, pH 6) buffer after incubation for 18 h at 37 degrees C. Positivity was revealed by the development of a pink to red color after addition of 2 drops of 1% extemporaneously prepared ferrous ammonium sulphate aqueous solution. Pyrazinamidase activity proved to be a useful characteristic for the differentiation of some species from other enterobacteria devoid of this property. Because of its simplicity, this test is suitable for its introduction into the miniaturized diagnostic kits for the identification of enterobacteria. PMID- 1298030 TI - Direction of hyphal growth: a relevant parameter in the development of filamentous fungi. AB - Macroscopic and microscopic measurements of the growth of Trichoderma viride and Rhizopus oligosporus were compared at different values of water activity of the solid medium. The relationship between radial extension rate and hyphal growth rate was found to be dependent on water activity. The observed difference between these two parameters was explained by the distribution of apical directions. The validity of the radial extension rate as a growth criterion could be discussed. The angular distribution of apical axes of growth in the front of the colony was observed at different water activity levels of the solid medium, and a model which links radial growth rate to hyphal growth rate and direction of apex growth was proposed and experimentally validated. PMID- 1298031 TI - A one-step microbial DNA extraction method using "Chelex 100" suitable for gene amplification. AB - "Chelex 100" chelating resin has been previously proposed for the rapid extraction of human DNA for polymerase chain reaction. Protocols are given for the rapid extraction of bacterial and viral DNA from cultures or clinical samples. The DNA samples obtained were suitable for use in polymerase chain reaction. PMID- 1298032 TI - [Determination of an ELISA test on tissues of grapevine affected by yellow disease]. AB - We report here results concerning the best part of the grapevine to section, the best sampling period and an important adaptation of the extraction media for the diagnosis of a grapevine yellow disease by ELISA. The addition of Triton-X100, or better of Chaps enabled us to get clear results for the sensitive Vitis vinifera scion varieties. Until now, results have not been obtained for the symptomless root stock varieties. However, antigen concentration by molecular filtration may be a way to solve the problem of assaying root stocks. PMID- 1298033 TI - Supplement 1991 (no. 35) to the Kauffmann-White scheme. PMID- 1298034 TI - [Books and reading for medical students]. PMID- 1298035 TI - [Ambulatory heart catheterization. Initial experience]. AB - Development of cardiovascular surgical techniques and more recently, balloon angioplasty, has resulted in a dramatic increase in the number of cardiac catheterizations performed. Previously, the usual policy was to admit the patient to the hospital for several days. Various series of patients submitted to ambulatory cardiac catheterizations have revealed that this procedure con be performed safely, with a potential reduction in hospital and patients costs, better utilization of medical beds and good image quality. In this study we present our initial experience in this kind of outpatient procedure. PMID- 1298036 TI - [Perspectives in medical genetics: the new genetics]. PMID- 1298037 TI - [Intra-nasal calcitonin for the prevention of postmenopausal osteoporosis]. PMID- 1298038 TI - [Cardiorespiratory arrest as a reason for admission to the ICU: clinical course and prognostic factors]. AB - The cardiac arrest is a situation associated with a abrupt and unexpected interruption of the spontaneous breath and circulation. It's a frequent cause to admit people in hospital. There the patients are admitted to the intensive care unit in order to care for them after cardiac arrest. We have studied 68 cases about cardiac arrest, their evolution, death rate and many factors usually described by another authors as prognostic of these patients. We encountered a higher mortality the longer the time of arrest, the higher the score on the Apache scale, on the lower the score on the Glasgow coma scale. Another point is if we aren't sure about the cause of the cardiac arrest or it's cerebrovascular accidents or upper airway failure, the prognostic is worse. Finally, if the ECG at the moment of the admission is asystole the death rate is 100%. PMID- 1298039 TI - [Teamwork]. PMID- 1298040 TI - Hypertrophic protein-losing gastropathy. A retrospective analysis of 40 cases in The Netherlands. The Dutch Menetrier Study Group. AB - Hypertrophic protein-losing gastropathy is a rare clinical entity of unknown etiology. Seventeen of 50 GI Units in The Netherlands, surveying their patient material, documented at least 1 positive case. Altogether, 40 patients (25 male and 15 female; mean age, 44.3 years) fulfilled the usually accepted criteria. Main complaints were epigastric pain (65%), asthenia (60%), anorexia (45%), weight loss 45%, edema (37.5%), and vomiting (37.5%). Hypoalbuminemia of < 35 g/l was found in 81%, and an abnormal enteric protein loss (51CrCl3) in 22 of 26 tested patients (85%). The mean basal acid output was 0.99 mmolH+/h. Stomach radiology in 35 patients showed giant folds mainly of the corpus mucosa; endoscopy confirmed the hypertrophy of the folds in all cases (in four confirmed by endosonography) and the presence of adherent mucus. Occasionally a concomitant gastric ulcer was found. Endoscopic biopsies were usually of limited value for the histologic diagnosis, mainly suggesting the possibility of hypertrophic gastropathy, excluding gastric cancer or lymphoma. In the follow-up 80% was treated with antacids, H2-receptor antagonists, mucosa-protectives, omeprazole, or combinations. No single agent appeared of major value. Eradication of Helicobacter pylori occasionally reduced symptoms. Twenty-two patients (55%) improved with or without medical therapy, during a mean follow-up of 7.6 years. Five patients (12.5%) underwent gastric surgery; four improved. In total, 26 patients (65%) improved, with partial or total regression of hypoalbuminemia. Eight patients died, three of gastric cancer, and five of cancers localized elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298041 TI - Effect of hyperglycemia on gastrointestinal and gallbladder motility. AB - Gastrointestinal motor abnormalities occur frequently in patients with diabetes mellitus. The gastrointestinal motor dysfunction in these patients has been associated with the presence of autonomic neuropathy. Recently, however, several studies have shown that the gastrointestinal motor responses to various stimuli are impaired during acute hyperglycemia in both healthy subjects and diabetic patients. It has been demonstrated that acute hyperglycemia impairs esophageal peristalsis, reduces the lower esophageal sphincter pressure, delays gastric emptying, slows intestinal transit, and reduces the gallbladder contraction in response to various stimuli in healthy subjects. In diabetic patients gastric emptying and gallbladder contraction have been shown to be impaired during hyperglycemia. With regard to the mechanisms of action, it has been suggested that hyperglycemia may affect gastrointestinal function through vagal-cholinergic inhibition, by alterations in serum osmolality, or perhaps by alterations in gastrointestinal hormone secretion. PMID- 1298042 TI - Intestinal permeability in pediatric gastroenterology. AB - The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense mechanisms. The non-immunologic mechanisms consist of intraluminal factors such as gastric acid, proteolytic activity, and motility and of mucosal surface factors like mucin and the microvillous membrane. The immunologic mechanisms include secretary IgA and cell mediated immunity. Both types of mechanism are not completely mature at birth. Maturation of this barrier is not finished before the 2nd year of life. One of the aspects of the mucosal barrier function can be estimated by the intestinal permeability (IP) for macromolecules. We use the differential sugar absorption test (SAT), in which the ratio of urinary excretion of a relatively large molecule, lactulose, is compared with that of a relatively small molecule, mannitol, after oral ingestion. Although the small intestine is permeable to certain macromolecules in normal developmental conditions, an increased IP could be involved in the pathophysiology of several diseases, including infectious diarrhea, food allergy, celiac disease, and Crohn's disease. It can be concluded that IP, as measured with the SAT, reflects the state of the mucosal barrier and is altered in several gastrointestinal diseases. The SAT is a non-invasive IP test that can be of diagnostic help to demonstrate alterations in the small mucosal barrier function and may be useful to evaluate therapeutic interventions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298043 TI - Helicobacter pylori: past, present, and future. AB - Helicobacter pylori has now been recognized as one of the most common chronic human infections. It has been accepted as an important aetiologic agent in non immune chronic gastritis and plays a key role in the aetiology of duodenal ulcer. It may also be involved in the pathogenesis of gastric cancer. PMID- 1298044 TI - Clinical application of 24-hour ambulatory esophageal pH and pressure monitoring. AB - Recently, 24-h recording of intraesophageal pH and pressure signals in ambulatory subjects has become possible. Several research applications of the technique have emerged, but until now only a few clinical applications have been established, the most important of which is noncardiac chest pain. In the computer analysis of the signals, the patient with noncardiac chest pain is used as his or her own control; motility and pH profiles during pain are compared with asymptomatic base line values obtained from the same patient. Automated analysis by means of a computer avoids observer bias and saves time. By means of 24-h monitoring, motor abnormalities have been identified as the cause of the chest pain in 4.5% to 18% and reflux in 4.5% to 25% of the patients studied. In addition, patients were identified who have both dysmotility- and reflux-related pain episodes. The yield of 24-h monitoring is highest in patients who have frequent pain episodes. A high yield of 24-h monitoring was found in patients with noncardiac chest pain admitted to a coronary care unit. Seventy-six per cent of these patients were found to have either reflux- of dysmotility-related chest pain. Patients with proven coronary artery disease who do not respond well to adequate treatment frequently have gastroesophageal reflux (39%) or esophageal motor abnormalities (50%) as the cause of their ongoing pain attacks. In these patients, identification of the esophageal cause of the symptoms not only helps the physician to select the optimal treatment but also reduces the patient's need for medical care. PMID- 1298045 TI - Gastric abnormalities in humoral immune deficiency syndromes. AB - Patients with late-onset hypogammaglobulinaemia have a very high risk of developing gastric cancer. In such patients there is a high frequency of atrophy of the gastric mucosa. This is reflected in low gastrin content of the antral mucosa, low serum pepsinogen A level and pepsinogen A/C ratio, and reduced serum gastrin secretion in response to bombesin stimulation. There is no evidence to support a role of Helicobacter pylori infection in the aetiopathology of these gastric abnormalities, although prior infection cannot be excluded with certainty. Since patients with early-onset hypogammaglobulinaemia and X-linked agammaglobulinaemia do not show this increased frequency of gastric abnormalities, it is unlikely that the immunoglobulin deficiency per se is responsible for the development of the gastric abnormalities found in patients with late-onset hypogammaglobulinaemia. Because of the very high risk of gastric cancer, regular endoscopic screening is warranted in patients with late-onset hypogammaglobulinaemia. PMID- 1298046 TI - Laparoscopic gastrointestinal and gallbladder surgery: will the promise be fulfilled? AB - The results of the first 181 consecutive patients who underwent laparoscopic cholecystectomy and 12 patients who underwent laparoscopic colon resection in our hospital are described. Our results show that laparoscopic cholecystectomy has proved to be the standard surgical procedure for treating gallbladder disease. The place of laparoscopic surgery in the treatment of other abdominal diseases is less clear. Our results in laparoscopic colon surgery indicate that a laparoscopic approach in segmental colon resection is feasible. The operation time is long, however, expressing the long learning curve for the operating team, as well as the technical difficulties encountered with this minimal invasive method. On the other hand, it has been proved that large abdominal operations can be performed via the laparoscope. By improving the laparoscopic instruments and increasing the laparoscopic surgeon's experience, further application of this method in gastrointestinal surgery may be expected. Surgeons should, however, be aware of the long learning curve involved in advanced laparoscopic surgery. PMID- 1298047 TI - A decade of experiences with radioimmunoassays for cholecystokinin in The Netherlands. AB - The radioimmunologic determination of cholecystokinin (CCK) has proved to be notoriously difficult. This is due to the specificity of antibodies, preparation of radiolabeled CCK and low CCK concentrations in human plasma. About 10 years ago we succeeded in developing two highly sensitive region-specific radioimmunoassays for CCK. Antibody T204 binds to the sulfated tyrosine region of CCK, while antibody 1703 reacts with biologically active molecular forms of CCK containing at least 14 amino acid residues. Both antibodies are devoid of significant cross-reaction with gastrin. By means of these two radio-immunoassays CCK concentrations were measured in both tissue and plasma of various species, including man. In addition, the molecular forms of CCK in tissue and plasma were characterized. These CCK assays were used to study the mechanism of CCK secretion. It appeared that digested rather than intact protein and fat stimulated CCK release from the small intestine. The physiologic and pathophysiologic role of CCK in humans was studied using CCK radioimmunoassays and specific CCK-receptor antagonists. CCK was found to play an important role in pancreatic enzyme secretion, gallbladder contraction, and gastrointestinal motility but possibly also in pancreatic carcinogenesis and regulation of satiety and satiation. PMID- 1298049 TI - Indications for surgical treatment of pancreatic cancer. AB - The best chance for cure of pancreatic cancer is surgical resection. This is also possible in case of adjacent organ involvement of, for example, duodenum, portal vein, or colon. Pancreatic tumours may develop to a large size without developing metastases. Irresectable tumours without distant metastases can successfully be treated with radiotherapy and 5-fluorouracil and, in some cases, be resected during a second-look operation. Thus there is no contraindication for laparotomy in case of large size. Preoperatively estimated size of the tumour is not of prognostic value for resection. Altogether, laparotomy is contraindicated only in case of distant metastases and high operative risk. PMID- 1298048 TI - Pharmacokinetics of ranitidine in a homogeneous population of intensive care unit patients during intermittent and continuous administration. AB - The pharmacokinetics of ranitidine during two different modes of intravenous administration was studied in a homogeneous group of postoperative intensive care unit patients (n = 18). Patients at risk of developing stress-related lesions were randomized to receive repeated injections, 50 mg every 6 h (group A), or a continuous infusion, 50-mg bolus followed by 0.125 mg/kg/h (group B). Before treatment all patients received a single 50-mg ranitidine dose. Serum ranitidine concentrations were measured for 12 h after the single dose and during the treatment period, to calculate individual pharmacokinetic variables. From the single-dose study the calculated half-life, volume of distribution, and clearance were 3.14 +/- 0.61 h, 1.45 +/- 0.42 l/kg, and 0.40 +/- 0.14 l/kg/h for group A and 3.33 +/- 1.08 h, 1.16 +/- 0.20 l/kg, and 0.35 +/- 0.21 l/kg/h, for group B, respectively. Ranitidine pharmacokinetics after the single dose was comparable in the two groups. No statistically significant differences could be detected between the ranitidine pharmacokinetics after the first single dose and the multiple dose or continuous infusion. PMID- 1298050 TI - CD4 antibody treatment in Crohn's disease. AB - Immunologic changes may play a role in the pathogenesis of Crohn's disease. Whether these changes are the primary cause of the disease or secondary to the inflammatory response remains unknown. Activated T helper cells probably play a pivotal role in Crohn's disease, although no causative antigen has been identified. Possible targets for immunomodulating therapy should include neutralization of the antigens, deletion of reactive activated T cells or, less specifically, interference with the antigen-presenting process. New, humanized, monoclonal antibodies that interfere with the antigen-presenting process are now available for clinical investigation. In particular, CD4 antibody treatment seems of interest, in view of the predominant role of T cells in Crohn's disease. Finally, because tumor necrosis factor is necessary for granuloma formation, inhibition of this factor may be expected to improve disease activity in Crohn's disease. PMID- 1298051 TI - Primary bile acid malabsorption: a pathophysiologic and clinical entity? AB - Primary bile acid malabsorption is defined as chronic diarrhoea with bile acid malabsorption of unknown cause and a symptomatic response to cholestyramine. Convincing evidence of the proposed pathophysiology--a defect of the active bile acid absorption in the distal ileum--has never been substantiated. We found no evidence of a bile acid transport defect across the ileal brush border membrane in 10 patients with primary bile acid malabsorption; moreover, transport was significantly higher than in a control group. In the patients with primary bile acid malabsorption the estimated bile acid pool was significantly larger than in a control group and in a group of patients with ileal disease. In addition, the oro-anal transit time of radiopaque markers was shorter in the primary bile acid malabsorption group than in both other groups. This suggests that the bile acid pool size as well as intestinal motility could play a role in the pathophysiology of primary bile acid malabsorption. PMID- 1298052 TI - Primary sclerosing cholangitis. An unresolved enigma. AB - Primary sclerosing cholangitis (PSC) is a disease of the bile ducts which frequently is associated with inflammatory bowel disease. The disease is characterized by stenoses and saccular dilatations of the intra- and/or extra hepatic bile ducts. Endoscopic retrograde cholangiography is the mainstay of diagnosis of this disease. A liver biopsy gives additional information and is particularly useful to rule out secondary cirrhosis. In a series of 50 patients the 5-year survival was 85%. The etiology is unknown, but in addition to inflammatory bowel disease the disease is associated with the autoimmune haplotype HLA-A1, B8, and DR3. Antibodies to perinuclear antigens in leukocytes are present in 65% of patients with PSC. Ursodeoxycholic acid therapy causes an improvement of symptoms and a decrease of elevated liver enzyme values. There are no drugs as yet with a proven effect on fibrosis or cirrhosis in this disease. Liver transplantation in this disease has a reported 4-year survival of 88%. PMID- 1298053 TI - Complications in obstructive jaundice: role of endotoxins. AB - Surgical treatment of patients with obstructive jaundice is associated with a high postoperative morbidity and mortality. A correlation was suggested between endotoxins and the observed complications. The mechanism by which endotoxins affect the negative outcome in operated jaundiced patients was, however, not clear, nor was the mechanism of clinically used preventive treatments. Several experiments were therefore performed in rats with biliary obstruction, to investigate whether and how endotoxins are active. The role of endotoxins was studied in a model in which endotoxins were absent. In germfree rats (free of bacteria and thus of endotoxin) the effect of biliary obstruction was studied and compared with biliary obstruction in conventional rats. To substantiate further the role of endotoxin, anti-endotoxin treatments (oral lactulose or internal drainage) were tested in rats with obstructive jaundice undergoing a severe surgical trauma. It is shown that endotoxins are responsible for complications (suppression of cellular immunity, kidney function, mortality) and that these complications can be prevented with an anti-endotoxin treatment. These results may have implications for preoperative treatment of jaundiced patients. PMID- 1298054 TI - New developments in hepatitis C. AB - Since the detection of hepatitis B virus (HBV) in the 1960s and hepatitis A virus in the 1970s, a considerable proportion of infections of (probably viral) hepatitis could not be classified. About 90% of transfusion-related hepatitis was identified as non-A/non-B. In 1988 investigators from the Chiron Company (USA) detected the non-A, non-B agent and named it hepatitis C virus (HCV). An anti-HCV antibody assay (ELISA) and subsequently confirmation tests (immunoblot and polymerase chain reaction) were developed. HCV infection results in a chronic carrier state of the virus in about 80%. Almost all HCV carriers have, irrespective of their liver function tests, histologic signs of chronic hepatitis and/or liver cirrhosis. Chronic HCV infection is, like HBV, also associated with the development of hepatocellular carcinoma. Most HCV carriers are infected by parenteral routes (intravenous drug use, blood transfusion, tattooing). Intravenous drug users and haemophilia patients have the highest risk (80-90%) of becoming infected. Sexual and perinatal transmission does not play an important role in spreading the infection. Antiviral therapy (alpha-interferon) in patients with chronic hepatitis C will normalize liver function tests in about 25% of the cases, but it is unclear if the HCV carrier state will disappear and if liver cirrhosis will be prevented. At present no specific immunoglobulin or vaccine preparations are available to prevent the HCV infection. PMID- 1298055 TI - Chemotherapy for gastrointestinal cancer: new hopes or new disappointments? AB - Since the end of the eighties relevant progress has been made in the treatment of gastrointestinal tract cancer, as well in advanced disease as in the adjuvant setting. The neoadjuvant treatment of localized esophageal and gastric cancer is of high interest, and especially the adjuvant treatment of colorectal cancer provides a realistic hope for further progress in the years not too far ahead. Results of recent studies with implications for future trials are discussed. PMID- 1298056 TI - Feeding via nasogastric tube or percutaneous endoscopic gastrostomy. A comparison. AB - When a patient needs enteral feeding, there are two methods to administer the nutrition. The method most used is the nasogastric tube (NGT), although in the literature little is published about the advantages and complications of the NGT. The second method is percutaneous endoscopic gastrostomy (PEG). A prospective randomized trial was started, and so far 90 patients have entered the study (46 NGT and 44 PEG). In four patients it was not possible to insert the NGT, and in three patients it was impossible to place the PEG. In both groups 6.5% aspiration was found. Nasal decubitus and swallowing problems were seen in 13% and 17%, respectively, in the NGT group. Intraperitoneal bleeding and abdominal pain were found in 2% and 11%, respectively, in the PEG group. Fixation of the patients was needed in 7% of the PEG and 22% in the NGT group. In eight patients in the NGT group the feeding had to be stopped owing to problems; in none of the PEG group was this necessary. The nursing staff awarded marks to each patient on a scale of 5 for the convenience of care (very good, 1; very bad, 5). This resulted in a mean score of 2.6 in the NGT and 2.0 in the PEG group. The score given by the patients was 2.3 in the NGT and 1.8 in the PEG group. There seems to be a clear preference for the PEG as a method for enteral nutrition. PMID- 1298057 TI - Gastric secretory abnormalities in duodenal ulcer: primary or secondary to Helicobacter pylori infection? AB - Hypersecretion of gastric acid, gastrin, and pepsinogen are considered to be causally related to duodenal ulcer diathesis. Until recently, these abnormalities have been considered to be primary and largely genetically determined. However, Helicobacter pylori infection has been shown to be responsible for several of the abnormalities of gastric secretion in duodenal ulcer. H. pylori infection is not only associated with chronic active inflammation but also with a reduction of somatostatin producing D-cells and somatostatin concentrations in the gastric mucosa. The reduced inhibitory action of somatostatin on the secretion of gastric acid, gastrin, and pepsinogen may be responsible for the hypersecretory state of the stomach in duodenal ulcer. These recent findings have drastically changed our understanding of the pathogenesis of duodenal ulcer. PMID- 1298058 TI - Tropical medicine, technology and economic development. PMID- 1298059 TI - Seameo Regional Tropical Medicine and Public Health Network. PMID- 1298060 TI - The college of public health, University of the Philippines Manila--meeting the challenge of health development. PMID- 1298061 TI - The development of nutrition training in Indonesia: the contribution of SEAMEO TROPMED. PMID- 1298062 TI - Seroepidemiological studies of malaria in different endemic areas of Indonesia. AB - A total of 618 sera from inhabitants living in various endemic areas in Indonesia were examined for IgG against Plasmodium falciparum utilizing young trophozoites and mature schizonts as antigens by the method of ELISA and IFAT. In general, antibodies against trophozites (RESA) based on ELISA and antibodies against schizonts based on IFAT showed a correlation of malarial antibodies with the level of endemicity of the area examined. Anti-RESA antibody, detected either by ELISA or IFAT was more pronounced in the aparasitemic group compared to the parasitemic group. On the contrary, anti-schizont antibody measured by IFAT was more pronounced in the parasitemic group. Malarial antibody levels against the schizont-merozoite fraction of P. falciparum as assayed by ELISA appeared to develop more slowly compared to levels based on IFAT. PMID- 1298063 TI - Health research in Malaysia: overview and future directions. PMID- 1298064 TI - Epidemiology and control of malaria in Malaysia. AB - In spite of more than 30 years of control activities, malaria continues to be the most important parasitic infection in Malaysia, accounting for 39,189 confirmed cases in 1991, giving an annual parasite incidence rate of 2.2 per 1,000 population. Some factors contributing to the continued transmission of malaria are the development of drug resistant Plasmodium falciparum, changes in vector behavior, and ecological changes due to socio-economic reasons. Malaria parasite rates are higher among the Aborigines, land scheme settlers and those in intimate contact with the jungle, like loggers. There has been no substantial change in the proportion of the three common malaria species responsible for infections, P. falciparum, P. vivax, P. malariae and mixed infections accounting for about 70%, 28%, 1% and 1%, respectively of all infections. Drug resistant P. falciparum is unevenly distributed in Malaysia, but based on clinical experience and in vitro drug sensitivity studies, chloroquine resistance is frequently encountered. There has been clinical and laboratory evidence of resistance to sulfadoxine/pyrimethamine combination as well as quinine, but all these have so far been successfully treated with a combination of quinine and tetracycline. The eradication of the disease is impossible in the near future but there is confidence that with better surveillance techniques and the use of alternative control measures like permethrin impregnated bed-nets to complement existing ones, the target of bringing down the annual parasite incidence to 2 per 1,000 population during the Sixth Malaysian Plan period (1991-1995) can be achieved. PMID- 1298065 TI - Intestinal protozoan infections in Malaysia. AB - Intestinal protozoa are found in all communities in Malaysia and among all ethnic groups. Prevalence of intestinal protozoa is not affected by ethnicity but by living conditions. Communities with both basic amenities of safe water supply and proper toilets have lower prevalence than those with one or none of the amenity. Cryptosporidium is an important intestinal protozoon in Malaysia and should be included in future field and laboratory studies and also in laboratory diagnosis for pathogens. Much interest will be centered on Blastocystis hominis in future studies in view that it may be a cause of diarrhea. PMID- 1298066 TI - Health research in the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. PMID- 1298067 TI - Immunological studies on some bacterial and parasitic diseases in Thailand. AB - Over the past two decades a wide range of immunological studies have been carried out on organisms responsible for causing serious bacterial and parasitic diseases in Thailand. Particular emphasis has been placed on cholera, where investigations have been directed towards vaccine development and rapid diagnosis and on diagnosis of typhoid and enterotoxigenic Escherichia coli. In the area of parasitic diseases emphasis has been directed especially to immunodiagnosis of helminthic diseases, including gnathostomiasis, paragonimiasis, opisthorchiasis, strongyloidiasis and trichinellosis. These studies are reviewed in this report. PMID- 1298068 TI - Drug resistant malaria, with special reference to Thailand. AB - Drug resistance of malaria parasites is a major problem confronting efforts to treat and control malaria. Starting with chloroquine, the emergence of resistance to other drugs has led to multi-drug resistance patterns that pose increasing threats for the future. This report reviews work carried out over the past decades at the Hospital for Tropical Diseases, Bangkok, which monitors patients from many areas, including the Thai-Cambodian border, which harbors the world's most severe multi-drug resistant Plasmodium falciparum. PMID- 1298069 TI - Global malaria challenge: the Amsterdam summit. AB - On 26-27 October 1992 the World Health Organization convened a global Ministerial Conference on Malaria in Amsterdam to draw up a global strategy for renewed attack on malaria, in view of the deteriorating situation in the control of this disease in many parts of the world. This report summarizes the key points of the strategy and the Declaration emanating from this crucial assembly of nations, which it is hoped will lead to increased tangible support nationally, from international agencies and from bilateral agreements for greatly improved programs of malaria control. PMID- 1298070 TI - Economics and tropical diseases: a research agenda using schistosomiasis as an example. AB - There is a growing interest in health economics in developing countries. In this paper, some of the economic literature concerning schistosomiasis is reviewed and a set of economic questions is derived which could form the basis of a broad research agenda for tropical diseases. The major criterion used to identify research issues is that they should be of practical value to control programs. PMID- 1298071 TI - Thalassemia in SouthEast Asia: problems and strategy for prevention and control. AB - In Southeast Asia alpha-thalassemia, beta-thalassemia, hemoglobin (Hb) E and Hb Constant Spring are prevalent. The gene frequencies of alpha-thalassemia reach 30 40% in Northern Thailand and Laos. beta-Thalassemia gene frequencies vary between 1 and 9%. Hb E is the hallmark of Southeast Asia attaining a frequency of 50-60% at the junction of Thailand, Laos, and Cambodia. Hb Constant Spring gene frequencies vary between 1 and 8%. These abnormal genes in different combinations lead to over 60 different thalassemia syndromes. The four major thalassemic diseases are Hb Bart's hydrops fetalis (homozygous alpha-thalassemia 1), homozygous beta-thalassemia, beta-thalassemia/Hb E and Hb H diseases. The molecular basis of most of these abnormal genes have been recently described. Therefore, it is possible to set a strategy for prevention and control of thalassemia which includes population screening for heterozygotes, genetic counseling and fetal diagnosis with selective abortion of affected pregnancies. PMID- 1298072 TI - Towards a malaria vaccine: riding the rollercoaster between unrealistic optimism and lethal pessimism. AB - Activity in many laboratories over the past decade has resulted in many vaccine candidates nearing clinical trials. These include several antigens from the sporozoite stage; merozoite surface antigens MSA1 and MSA2, RESA, the rhoptry proteins RAP-1 and RAP-2 from the asexual blood stage; the pfs25, pfg45 and pfg230 from the ookinete and gamete stages. This progress in the identification of potential vaccine candidates now highlights a series of scientific, developmental, economic and operational problems the solutions to which will be as critical to the development of a vaccine as the cloning and expression of parasite genes. PMID- 1298073 TI - Neurological complications of malaria. AB - This paper reviews the neurological complications of malaria. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red blood cells causing blood sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes a nonspecific, immune-mediated, inflammatory response with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations in malaria remains unexplored, but offers excellent perspectives for research at clinical as well as experimental level. PMID- 1298074 TI - Importance of ecology in Aedes aegypti control. AB - Aedes aegypti is one of the world's most widely distributed mosquitos and is of considerable medical importance as a vector of dengue and yellow fever. Not surprisingly therefore there has been more written on its biology than any other mosquito. The present paper summarizes ecological studies undertaken on this vector, including those on pre-adult mortalities, life-tables, adult dispersal and survival rates. In discussing surveillance techniques it is pointed out there are still no reliable methods for monitoring adult populations. The importance of the resting habits of adults and house construction in insecticidal control of Ae. aegypti is discussed. The question is, have ecological studies and population modeling resulted in any more understanding of the epidemiology of dengue, or helped formulate better control strategies? The answer seems to be not usually, possible because there have actually been relatively few good ecological studies on Ae. aegypti. Although mathematical modeling indicates that better control might be achieved if it were directed at the larvae, not adults, this has not usually been taken into consideration by those engaged in control. There is clearly need for greater collaboration between those practicing control, and ecologists and modelers. PMID- 1298077 TI - Streptococcal throat carriage in school children with special reference to seasonal incidence. AB - A number of studies on throat carriage of beta hemolytic streptococci (BHS) carried out during the years 1972-90 in urban and rural school children from low socioeconomic groups in the age group of 5-15 years in and around Delhi showed an overall carriage rate of BHS varying from 12.2%-64.3% depending upon the season and number of swabs taken. Group A was found to be the most predominant serological group (31.1%-62.6%). The T-typability was found to be 98.2%. The most prevalent T-patterns observed during 1972-78 study were 3/13/B3264 followed by 5/11/12/27/44. A significant difference was observed in the prevalence of T patterns during the study of 2,034 children from 1979-83 and 3,094 children from 1984-90. When the most prevalent T-patterns were found to be 5/11/12/27/44 followed by 3/13/B3264. The study of the school children from 1972-90 showed the isolation of BHS as well as significant predominance of GAS (p < 0.001) in winter months than summer months. There was no difference in the distribution of carriage of BHS and GAS amongst rural or urban school children. Since RF/RHD are illnesses which were often encountered in school children among socially and economically disadvantaged populations stronger support for streptococcal surveillance programs should be encouraged. PMID- 1298075 TI - Iron status of pregnant Filipino women as measured by serum ferritin. AB - Iron status of pregnant women at different stages of pregnancy was evaluated by comparing values for hemoglobin (Hb), red cell indices, serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) values with those of a group of non-pregnant women of comparable age and socio-economic status. Mean SF values on the second and third trimesters (9.3 +/- 2.60 ng/ml and 7.1 +/- 2.19 ng/ml) were significantly lower compared to that in the first trimester (22.6 +/- 2.20 ng/ml). These levels were also lower than that found in the non-pregnant controls. The trend was the same for TS. Hemoglobin levels of the pregnant subjects were significantly lower than those of the non-pregnant women. Prevalence of iron deficiency based on SF < 12.0 ng/ml and TS < 16.0% was highest at term and lowest during the first trimester indicating a decrease in iron stores as pregnancy progressed. Sensitivity for each of the iron parameters was computed, and it was found that for the diagnosis of iron deficiency in pregnant women, SF has a greater sensitivity than TS, SI, MCV and MCH. PMID- 1298076 TI - Hypercalcemia in active pulmonary tuberculosis and its occurrence in relation to the radiographic extent of disease. AB - The prevalence of hypercalcemia in tuberculosis in Hong Kong and its occurrence in relation to the radiographic extent of disease were studied in 57 patients with sputum smear (n = 44) and/or culture positive (n = 13) pulmonary tuberculosis and in five patients with military tuberculosis prior to treatment. Only one (1.6%) patient had a corrected plasma calcium level above the reference range for our laboratory. There was a positive relationship between the corrected plasma calcium levels and the radiographic extent of disease (r = 0.37), p < 0.01). As the occurrence of hypercalcemia in tuberculosis is known to be influenced by the calcium intake, our finding of a low prevalence of "absolute" hypercalcemia in Hong Kong could be related to the low dietary calcium intake in these subjects. PMID- 1298078 TI - Pulmonary pathology in rabbits infected with the Baling and Koyan strains of Schistosoma malayensis. AB - Two distinct strains of Schistosoma malayensis exist in Malaysia (designated the Baling and Koyan strains). Both these strains show intraspecific variations in pathology (Greer et al, 1988). To evaluate the differences in the pulmonary pathology resulting from infections of the two different strains of Malaysian schistosome, a total of 20 experimental rabbits were infected, 10 each with cercariae of the Koyan strains. Pathological changes were studied over a period of 28 weeks. Granulomas in the lung occurring as a result of infection with the Baling strain were compared with those caused by infection with the Koyan strain. Although both strains produced parenchymatous and alveolar lesions, granulomas caused by the Baling strain of Malaysian schistosome were more numerous and larger (when comparing mean diameter as well as area of granuloma, p < 0.05). In addition, pulmonary vascular hypertensive changes were present in Baling strain infected rabbits. These comprised of pulmonary arteriolar endothelial swelling and damage, intimal elastosis and medial hypertrophy. Angiitis and pulmonary periphlebitis were also noted occasionally. In contrast, Koyan strain infection resulted in fewer and smaller granulomas. Pulmonary vascular changes were minimal. PMID- 1298079 TI - Albendazole stimulates outward migration of Gnathostoma spinigerum to the dermis in man. AB - Human gnathostomiasis is characterized by space-occupying inflammatory lesions and/or hemorrhage as a result of the migration of, very often, a single larva of Gnathostoma spinigerum. Intermittent cutaneous migratory swellings occurring over years is the most common manifestation and the rare cerebral invasion may be fatal. There are currently no effective anthelminthics for this infection. During a double-blind randomized placebo control trial evaluating the efficacy of albendazole in cutaneous gnathostomiasis at a dosage of 400 mg twice daily for two weeks, it was observed that gnathostome larvae tended to migrate outward as a result of the treatment so that they could be recovered by excisional biopsy or by picking with a needle. In the placebo-treated group (N = 40), no such migration was observed during the 8,470 patient-days of follow-up while in the albendazole-treated group (N = 41) there was one worm in an excisional biopsy done on day 16 and two worms were removed from the skin by the patients themselves on days 8 and 0. Assuming that the period of drug exposure of the gnathostomes was the 14 days of albendazole administration plus another washout period of 7 days (equivalent to 20 half-lives of the active detectable metabolite), the total patient-days of albendazole exposure was 830. The rate of outward migration of gnathostomes in the drug treated group (3 per 830 patient days) was significantly (p < 0.0001) higher than in the placebo group (0 per 8,470 patient-days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298080 TI - Problems in dengue control: a case study. AB - The control of dengue outbreak requires a multi-pronged effort by the various government agencies. It requires co-operation of the community in the control activities, strict adherence to existing control procedures and guidelines by health personnel, increased manpower where necessary and strengthening co operation between various health agencies to prevent delay in instituting control measures. PMID- 1298081 TI - IgM capture ELISA for detection of IgM antibodies to dengue virus: comparison of 2 formats using hemagglutinins and cell culture derived antigens. AB - The highly sensitive AFRIMS format IgM capture ELISA for the diagnosis of dengue virus infections requires the use of mouse brain derived hemagglutinins and consequently also the use of 20% acetone extracted normal human serum to eliminate high background. These reagents are not always easily available and we have thus compared the AFRIMS format with another published format which uses cell culture derived antigens (culture fluid, CF, format) in order to determine if it is reasonable to use cell culture derived antigens in situations where hemagglutinins and normal human serum are difficult to obtain. The study shows that using AFRIMS results as the reference point, the CF format described here has a sensitivity of 90% and a specificity of 96%. PMID- 1298082 TI - Detection of circulating plasmodial antigens in human sera by sandwich ELISA with monoclonal antibodies. AB - Two monoclonal antibodies (MAbs), one produced against Plasmodium falciparum (PF IG8) and the other against P. cynomolgi (PC-IE12) schizont antigens were used in a sandwich ELISA for the detection of circulating plasmodial antigens in sera of patients infected with either P. falciparum, P. vivax or P. malariae. The mean +/ SD optical density (OD) values for the normal control group using PF-108 and PC 1E12 were 0.351 +/- 0.036 and 0.205 +/- 0.044, respectively. Mean OD values for the three infected groups were found to be significantly higher than those of the normal control group for both MAbs. However, ELISA values for individual serum specimens did not correlate with the level of parasitemia in the infected blood. Using a cut-off point of mean OD +/- 3 SD of the normal control group as indicating a positive reading, the specificity of this assay with both MAbs was 100%. The sensitivity of the assay using PF-1G8 was 95% while that obtained with PC-1E12 was 98%. PMID- 1298083 TI - Two-site pan-species monoclonal antibody ELISA for detection of blood stage malaria antigen. AB - A two-site pan-species monoclonal antibody sandwich ELISA (MAb-MAb ELISA) was developed to detect both Plasmodium vivax and P. falciparum antigens in whole blood impregnated on filter paper. In this assay, the plates were coated with pan species MAb 3F9 and another pan-species MAb M26-32 conjugated with alkaline phosphatase was used for detection of bound antigen. The sensitivity of this assay was 5, 10 and 10 parasites per 10(6) erythrocytes for cultured P. falciparum, patient-derived P. vivax and P. falciparum, respectively. The coincidence rates for this assay were 93% (92/99) with healthy individuals and 93% (42/45) with microscopically confirmed vivax malaria cases. After two weeks treatment, 77.7% (14/18) of vivax malaria were still positive by this assay but with diminished level of reactivities [corrected]. PMID- 1298084 TI - Two-site sandwich ELISA for detection of Plasmodium vivax blood stage antigens using monoclonal and polyclonal antibodies. AB - Two systems of sandwich enzyme-linked immunosorbent assay (ELISA), a two-site monoclonal antibody sandwich ELISA MAb-MAb sandwich ELISA) and a two site polyclonal-monoclonal antibody sandwich ELISA (PAb-MAb sandwich ELISA) for the detection of Plasmodium vivax antigens were developed. The assays showed good correlation with the level of parasitemia when tested against serially diluted P. vivax parasites (r = 0.937, and 0.997 for MAb-MAb and PAb-MAb sandwich ELISA, respectively), with the ability to detect as few as 6.68 parasites/10(6) erythrocytes and 2.69 parasites/10(3) erythrocytes, respectively. The MAb-MAb sandwich ELISA was specific, since it was positive only with P. vivax-infected erythrocytes from vivax malaria patients and negative when erythrocytes from 34 healthy individuals and 30 falciparum malaria cases were tested. In contrast, cross-reaction was found in the PAb-MAb sandwich ELISA when the plates were coated with polyclonal IgG and tested against the serially diluted P. falciparum SO strain antigen prepared from in vitro cultures. Comparison between the two systems of two-site sandwich ELISA showed that the MAb-MAb sandwich ELISA was superior to the PAb-MAb sandwich ELISA: (1) it gave a higher sensitivity when tested with serially diluted P. vivax antigen preparations from vivax malaria patients; (2) it gave a higher specificity when tested with the SO strain of P. falciparum from in vitro cultures, (3) it gave a lower absorbance value when tested with erythrocytes from healthy individuals. All 281 cases of vivax malaria already proven by microscopic examination were positive by MAb-MAb sandwich ELISA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298085 TI - Antibody detection ELISAS for malaria diagnosis. AB - Parasite extracts of Plasmodium falciparum and P. chabaudi and three synthetic peptides from the P. falciparum MSA2 merozoite antigen were tested for suitability as antigens in an antibody detection ELISA using sera from malaria patients in Brisbane. The P. chabaudi extract was superior to P. falciparum extract for detecting P. vivax cases, while for P. falciparum cases the two parasite extracts were equivalent. Single peptide antigens were generally less sensitive than parasite extracts; however, peptides G3 and G7 were more sensitive than parasite extracts in detecting first attacks of P. vivax. Examination of isotype specific responses demonstrated that this may be explained by higher IgG responses to these peptides in first than in subsequent P. vivax attacks. Because of the differing antibody specificities in primary and secondary P. falciparum and P. vivax cases, the best sensitivity was achieved by using the combined results of assays with three antigens: P. chabaudi, peptide G3 and peptide G7. The combined sensitivity was 77.1% for P. falciparum and 88.6% for P. vivax acute cases with 91.1% specificity. PMID- 1298086 TI - Artemether in the treatment of multiple drug resistant falciparum malaria. AB - Artemether has the potential to be an alternative antimalarial for multiple drug resistant falciparum malaria. However, it has been associated with high recrudescent rates which may be due to incorrect dosage regimens. The dosage regimens are varied from country to contry. We have carried out a comparative study of two dosage regimens, ie 480 mg and 600 mg total dose given over 5 days in uncomplicated and severe falciparum malaria. 167 patients were included in the study, 61 with acute uncomplicated falciparum malaria and 106 with severe malaria. All patients showed a good initial response. The difference in total dose had no effect on the parasite or fever clearance time (PCT or FCT). However, the severity of the disease did have some influence of these times. The PCT and FCT from either regimen of uncomplicated malaria were significantly faster than those of severe malaria (p < 0.005 and = 0.05, respectively). The cure rate seems to have some correlation with the amount of drug given and severity of the disease. The cure rates in uncomplicated malaria were 84 and 92%, respectively, for 480 mg and 600 mg. In severe malaria the cure rates dropped to 65 and 76%, respectively, for 480 and 600 mg. We conclude that artemether can be considered as an alternative antimalarial for multiple drug resistant falciparum malaria. However, the cure rate of severe falciparum malaria in this study is not considered satisfactory in areas with multiple drug resistant falciparum malaria. Further studies are needed to assess the curative efficacy with different dosage regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298087 TI - Preliminary report: a comparative clinical trial of artemether and quinine in severe falciparum malaria. AB - Twenty-six patients with severe falciparum malaria were randomized to be treated with quinine or artemether. Twelve patients received quinine at the standard dose and fourteen patients received artemether intramuscularly at a total dose of 640 mg over 7 days. The patients were kept in the hospital for at least 7 days. Peripheral smear was performed 6-hourly until there was no parasitemia, then daily until discharged. Adverse effects were monitored through physical examination, laboratory findings and questionnaires. Laboratory examination was performed on admission, day 2, day 4 weekly until discharged. The patients in both groups were comparable in age, body weight, admission parasitemia, hemoglobin and white blood cell count. The survival rates were 93% and 58% in artemether and quinine groups, respectively (p = 0.052 at 95% confidence, using Fisher's exact test). The parasite and fever clearance times, and the time taken to gain consciousness in cerebral malaria patients were not significantly different between the two groups. Adverse effects in the quinine group consisted of dizziness and vertigo which were found in 4 patients. No adverse effects were noticed in the artemether group. This preliminary report suggests that artemether is a good alternative drug for severe falciparum malaria and seems to be better than quinine regarding survival rate and side effects. Confirmation of these findings in a larger study size is needed. PMID- 1298088 TI - Pharmacokinetics of quinine, quinidine and Cinchonine when given as combination. AB - Pharmacokinetics of quinine, quinidine and cinchonine when given as a combination were evaluated in Thai patients with falciparum malaria during acute infection and convalescence. The combination of quinine, quinidine and cinchonine was randomly given to thirteen patients at 400 mg or 600 mg (consisting of one-third of each component; 7 patients were enrolled in 400 mg regimen and 6 in 600 mg regimen) intravenously every 8 hours for 7 days. The drug combination was given again at day 35 to define the pharmacokinetics of each drug during convalescence. All patients with the 600 mg regimen had good response with 100% cure rate while patients with the 400 mg regimen had a good initial response but one patient recrudesed on day 46. This particular patient had plasma concentrations of all three drugs lower than the mean values of patients with sensitive responses. The plasma levels of quinine and quinidine obtained from the present study were higher than that expected from one-third of the conventional dose (600 mg) when given alone, suggesting drug combination interaction. The terminal half-lives of each of the three components were prolonged during acute malaria when compared to those obtained during convalescence. PMID- 1298089 TI - Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial. AB - At a time when Fansimef, the fixed combination of mefloquine, sulfadoxine and pyrimethamine was considered for prophylaxis of falciparum malaria, a randomized double-blind study comparing the efficacy and tolerability of Fansimef with that of Lariam (mefloquine), Fansidar, chloroquine and placebo in malaria prophylaxis was performed in Thailand from July 1987 to January 1988. The study population of 602 adult males was recruited in Pak Tongchai District, some 360 km North-East of Bangkok, where multiresistant P. falciparum is endemic. All active treatments and placebo were given once weekly for 24 weeks with doses as follows: Fansimef: 125 mg mefloquine + 250 mg sulfadoxine + 12.5 mg pyrimethamine (1 half-strength tablet); Lariam: 125 mg mefloquine (1 half-strength tablet); Fansidar: 500 mg sulfadoxine + 25 mg pyrimethamine; chloroquine; 300 mg. A loading dose of 2 half strength tablets was given in the Fansimef group in weeks 1 and 2 and in the Lariam group in weeks 1 to 4. The incidence of acute episodes of P. falciparum per 100 person months of prophylaxis was 0.17 each in the Fansimef and the Lariam groups, 1.18 in the Fansidar group, 0.69 in the chloroquine group and 0.64 in the placebo group (differences statistically not significant). Clinically adverse events were reported by 170 subjects (Fansimef 28, Lariam 29, Fansidar 41, choroquine 43, placebo 29; differences statistically not significant). The most frequent adverse events in all groups were headache, sleepiness, dizziness and weakness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298090 TI - Malaria in a rural area of eastern Thailand: baseline epidemiological studies at Bo Thong. AB - Malaria is still a serious health problem in Thailand. Present attempts at controlling the disease by drug treatment and other means remain unsatisfactory. Thus, development of vaccination against malaria is a major research goal of malaria immunology. The objective of this study was to acquire epidemiological base line data for subsequent vaccine trials. A cross-sectional descriptive survey was conducted among 253 local inhabitants during the beginning of the transmission season in July 1989 at Bo Thong District, Chonburi Province, Eastern Thailand where malaria transmission was likely to be moderately high. Following the cross-sectional survey weekly morbidity surveillance was started to detect new cases of malaria by using active and passive case detection at the district hospital, local health centers and at neighboring malaria clinics. Fifty-four percent of the population were male and forty-six percent female: nearly a half (48.3%) were under the age of 15 and 17% under the age of 5 years. Eighty percent of the adults were married. Seventy percent of the subjects interviewed gave a history of malarial illness in the past. Malaria, malnutrition, anemia abnormal hemoglobin diseases and parasitic infestations were the main health problems in the study area. The annual parasite incidence of malaria was 169.4/1,000 population and 77% of parasitemic individuals were asymptomatic, indicating the existence of a semi-immune condition among these subjects. Antibody level to crude parasite antigen increased with age. It is hoped that the information obtained from these field studies may be useful in malaria vaccine trials in the near future. PMID- 1298091 TI - Dyspepsia in acute falciparum malaria: a clinico-pathological correlation. AB - Gastrointestinal symptoms are common in acute falciparum malaria. Dyspepsia often occurs in such patients and sometimes it is exceptionally severe. However, the pathogenesis of the dyspeptic symptoms in malaria has not been clearly defined. Upper gastrointestinal endoscopy was performed in 40 patients with acute falciparum malaria in order to correlate the dyspeptic symptoms with the macroscopic (endoscopic) and microscopic (histologic) pathology of stomach and duodenum. The patients were divided into a dyspeptic group (n = 20, male/female ratio = 17/3, age range 18-50 years, mean age = 28.85 + 9.14 years), and a non dyspeptic group (n = 20, male/female ratio = 16/4, age range 15-47, mean age 26.05 + 9.98 years). The findings revealed that dyspepsia correlated with topographic endoscopic pangastritis (p = 0.0014), the category of endoscopic antral gastritis (p = 0.013), and the histologic severity of antral gastritis (p = 0.0434). The results suggested that gastritis should be considered in acute falciparum malaria patients presenting with dyspepsia. PMID- 1298092 TI - Eosinophilic response to falciparum malaria infections. AB - Eosinophilia was a frequently detected incidental finding during a prospective study of malaria seroepidemiology in Thailand. Blood eosinophil counts were performed every 3 months for a year in 823 Thai soldiers on border guard duty in a malaria endemic area. Soldiers developing malaria were admitted to hospital and more frequent eosinophil counts were done. P. falciparum parasitemia suppressed preexisting eosinophilia but eosinophilia returned following treatment. P. vivax and mixed infections had a similar but less marked effect on the peripheral blood eosinophil count. Eosinophilia in persons from a malaria endemic area may represent a normal late response to malaria infection. PMID- 1298093 TI - Incrimination of Anopheles aconitus Donitz as a vector of epidemic malaria in Bangladesh. AB - In 1989-91, post-monsoon epidemics of vivax malaria occurred in the central flood plain near Dhaka. Anopheles philippinensis, the usual vector in the paddy field habitat, was not present, but 1.4% of parous An. aconitus were infective. This is only the second time An. aconitus has been incriminated as a vector in Bangladesh. We speculate that the surprising increase in lowland malaria may have been caused by environmental change that favored the survival of An. aconitus. PMID- 1298094 TI - The prevalence of helminth infection in Ban Nanin, Laos: additional data. PMID- 1298095 TI - Eight cutaneous leishmaniasis cases detected in Karamay, Xinjiang Uygur Autonomous region, China. PMID- 1298096 TI - Rapid detection of hepatitis B surface antigen by red cell agglutination assay. PMID- 1298097 TI - Myiasis in human filarial lymphedema. PMID- 1298099 TI - A frame for defining social work in a hospital setting. AB - A frame for articulating the unique role of social work in a hospital setting is presented which links the patient's experience of the disruptive impact of illness and hospitalization with the historical roots of the profession of social work. The presentation emphasizes the social worker's role in orienting patients and families to the importance of their part in the process of healing and helps partialize this task into specific areas of work with the social worker. A consideration of the process of discharge planning within this framework is discussed. PMID- 1298098 TI - Studies of hospital social stays in the frail elderly and their relationship to the intensity of social work intervention. AB - The elderly frequently suffer long lengths of hospital stay (LOS). These long stays are often associated with long social care stays which occur when patients no longer require acute care and are awaiting post-discharge services. In this study, actual acute care LOS and social care LOS were studied specifically in hospitalized frail elderly. Our data demonstrate that frail elderly receiving only acute care do not suffer markedly prolonged total LOS (TLOS). However, in hospitalized frail elderly patients who experience acute care and social care stays, social care LOS accounts for over half of all hospital days. When patients were grouped and studied according to the type of post-discharge services being sought by the health care team, significant differences in acute LOS and social care LOS were noted. Subgroups of patients were also identified among the various groups which differed significantly in their LOS parameters. Patients who required more than one discharge plan during the course of hospitalization experienced the longest hospital stays of all groups, and spent almost 70% of these days receiving non-acute social care. In a study of the relationship between the intensity of social work intervention and social care LOS in the frail elderly, a statistically significant relationship was noted between the timing and frequency of social work intervention and the actual length of social care stays. Early and frequent social work interventions were associated with significantly shorter social care LOS. We conclude that the study of TLOS should include acute LOS and social care LOS to obtain a reliable measure of the course and cost of hospital care for the frail elderly. The study of social care subgroups may facilitate future investigations to define the social care problems which contribute most to TLOS, and the patient populations which should be most heavily targeted for early and intensive social work intervention. PMID- 1298100 TI - Social work with multi-family groups: a partnership model for long term care settings. AB - Residents in long term care facilities suffer from physical and cognitive impairments. As their conditions deteriorate, it is often difficult for families to maintain significant ties with them. Social work can help family members develop meaningful roles in the institution via multi-family groups, an approach which enhances the contributions families can make at a time when family ties and roles need to be redefined. The program has been replicated on all floors in one facility and can be adapted to other settings. PMID- 1298101 TI - Critical incident stress: the role of hospital-based social work in developing a statewide intervention system for first-responders delivering emergency services. AB - Emotional, cognitive and behavioral stress can negatively affect the performance of fire, rescue and law enforcement personnel responding to emergency situations. Impaired professional performance in these crises not only endangers the incident victims, all involved responders and their families, but potentially the lives and property of entire communities. This article describes the major administrative and clinical leadership of a hospital-based Social Work department in implementing one of the few statewide critical incident stress debriefing teams for emergency service personnel in the United States. It represents a model for program development by other organizations. PMID- 1298102 TI - Helping Holocaust survivors with the impact of illness and hospitalization: social work role. AB - Illness and hospitalization can trigger intense reactions for Holocaust survivors and their families which derive from the brutal and dehumanizing experiences they endured during World War II. Some characteristic problems and reactions to illness and hospital care they and their families experience are reviewed, as are indicated social work interventions based on crisis theory. PMID- 1298103 TI - The role of computerized information systems in quality assurance in hospital social work departments. AB - Computerized information systems can be valuable tools in the total quality assurance program of hospital social work departments. This paper presents a matrix of potential roles for the information system at various levels of assessment-structural, process, and outcome. It then illustrates these roles, based on examples from a country-wide information system developed for hospital social work departments in Israel. PMID- 1298104 TI - Discriminators of willingness to consider cadaveric kidney donation among black Americans. AB - Black Americans were classified as either willing or unwilling to consider serving as kidney donors according to a combination of demographic and social psychological variables. Findings indicated that, in addition to selected religious variables, willingness to consider donation was associated with gender, age, source of information about organ donation, perceived need for transplants among blacks, self-acceptance of transplant organs and perception of bias in the selection of transplant recipients. Implications of the findings for social work practice and future research are discussed. PMID- 1298105 TI - Herniation of calcified cervical intervertebral disk in children. AB - Childhood intervertebral disk calcification is a rare clinical entity and usually has a benign course, generally undergoing spontaneous resolution. However, rapid neurologic deterioration due to herniation, found in both of our cases of calcified cervical intervertebral disks, required urgent anterior discectomy and fusion, resulting in excellent recovery. PMID- 1298107 TI - Temporal lobectomy for complex partial seizures that began in childhood. AB - Forty-six consecutive patients who underwent surgery for intractable temporal lobe seizures originating in childhood are reported; invasive preoperative monitoring (e.g., depth electrodes and subdural arrays) was not used in the selection process. Our results, with respect to the control of seizures and improvement in behavior, are comparable to those of series in which invasive monitoring was used in the selection process. Eighty-five percent of the 46 patients (96% of the 28 operated after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced near total control of their seizures. Our results indicate that many patients can be selected successfully for temporal resection without exposure to the risk and expense of invasive presurgical procedures. A long duration of epilepsy prior to surgery in patients with neoplasia portended a less satisfactory outcome. Our results strengthen the argument for early operation in children with intractable epilepsy. PMID- 1298106 TI - Predictors of mortality in severely head-injured patients with civilian gunshot wounds: a report from the NIH Traumatic Coma Data Bank. AB - Predictors of outcome were examined in this prospective study of 151 patients severely injured by civilian gunshot wounds. Of the 151 patients, 133 (88%) died. Of the 123 patients with an initial Glasgow Coma Scale score of 3-5, 116 (94%) died, whereas of the 20 with an initial Glasgow Coma Scale score of 6-8, 14 (70%) died. There were no good outcomes, and only three moderate recoveries in patients who had initial scores of 8 or less. In those patients who survived long enough for intracranial pressure monitoring, intracranial hypertension predicted a very poor outcome. Computed tomographic scan characteristics such as midline shift, compression or obliteration of the mesencephalic cisterns, the presence of subarachnoid blood, intraventricular hemorrhage, and the presence of hyperdense or mixed-density lesions greater than 15 mL, either bilateral or unilateral, were all associated with a poor outcome. However, neither the caliber of gun nor the distance of the gun from the head significantly affected the risk of dying. PMID- 1298108 TI - Transcranial Doppler waveform differences in hyperemic and nonhyperemic patients after severe head injury. AB - Although increased cerebral blood flow velocity is readily measured by transcranial doppler ultrasonography (TCD), the causes of the velocity elevation may differ. After severe head injury, increased blood flow velocity can develop both in patients with global hyperemia (suggestive of vasodilation) and in those without hyperemia (suggestive of vasospasm). The present study attempts to determine whether TCD can differentiate these two mechanisms of velocity increase. Fourteen severely brain-injured patients who developed increased middle cerebral artery blood flow velocity (time-averaged mean velocity > 100 cm/s) were studied. Eight cases were nonhyperemic and six were hyperemic as defined by arterial-jugular venous oxygen content differences of more than 4 mL/dL and less than 4 mL/dL, respectively. The TCD waveform of all eight nonhyperemic cases showed a diastolic notch, which was absent in all six hyperemic patients (p = 0.00066). TCD waveform profile appears to provide a noninvasive means of differentiating at the bedside the two causes of increased flow velocity. If associated with raised intracranial pressure, these require different treatment. PMID- 1298109 TI - Massive bifrontal epidermoid tumor. AB - There have been 27 cases of epidermoid tumor reported to arise from the frontal or ethmoid sinus area. We report the case of a virtually asymptomatic massive bifrontal epidermoid tumor arising from the ethmoid sinus in a 76-year-old male. PMID- 1298110 TI - Clinical and neuroradiological correlations in a patient with a wandering retained air gun pellet in the brain. AB - The authors present the case of a patient with an air gun pellet that moved from the ventricular system into the subarachnoid space of C2-C3, from where it was successfully removed by interlaminotomy. PMID- 1298111 TI - Postoperative central conduction time and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage: relationship with prognosis and ischemic conditions. AB - Cerebral blood flow (CBF) and somatosensory evoked potential (SEP) were monitored periodically on 32 patients who underwent aneurysm clipping within 3 days after subarachnoid hemorrhage (SAH). From the SEP data, central conduction time (CCT) was obtained, and CCT fluctuations were categorized into three types. Patients with CCT prolongation over 7.5 ms within 10 days after SAH tended to have poor recovery of CBF and unfavorable outcome. Therefore, periodical monitoring of CCT was considered as a useful indicator for predicting prognosis and post-SAH changes of cerebral blood flow. PMID- 1298112 TI - The history of neurosurgical procedures for the relief of pain. AB - Pain has been a major medical problem from the beginning of recorded history. Since the earliest medical writings, there have been innumerable procedures designed to relieve pain and its suffering. In this study, we have reviewed both the early medical writings of various civilizations and the first modern publications, to compile a history of neurosurgical procedures for the relief of pain. PMID- 1298113 TI - Dorcas Hager Padget: artist and embryologist. AB - Dorcas Hager Padget (1906-1973), a largely self-taught illustrator, became a more polished artist under Max Brodel at Johns Hopkins Hospital, before going to work for neurosurgeon Walter Dandy. In search of more information on vascular anatomy, she became an expert neuroembryologist, first in the development of arteries and veins and later chiefly involved with anomalies of neural tube development. She was able to clarify the development of the Arnold-Chiari and Dandy-Walker syndromes. PMID- 1298114 TI - Unusual craniocerebral penetrating injury by a power drill: case report. PMID- 1298115 TI - Training of future neurosurgeons. PMID- 1298116 TI - [Inhibiting effect of domestic, synthetic beta-carotene and ascorbic acid on endogenous carcinogenesis in mice]. AB - Carcinogenesis in mice induced by the tryptophane derivative 3-hydroxyanthranilic acid was studied after administration of synthetic beta-carotene and ascorbic acid. The incidence of induced hemoblastoses and hepatomas was decreased 2-fold, while the latent period of their development was, increased in mice on a lifetime feed containing 15 mg/kg of beta-carotene. The anticarcinogenic effect of ascorbic acid added to drinking water was similar to that of beta-carotene. The additive inhibitory influence of beta-carotene and ascorbic acid on endogenous blastomogenesis was not found in mice. PMID- 1298117 TI - [Preventive effect of domestic, synthetic beta-carotene on the development of rat mammary tumors induced by DMBA]. AB - Preventive effects of artificial beta-carotene on the development of rat mammary gland adenocarcinomas induced by DMBA were studied in rats maintained on a diet containing beta-carotene at a dose of 2.5 mg per animal within 10 weeks, which was initiated after the carcinogen administration. The carotenoid treatment course caused the following effects: manifestation of adenocarcinomas induced by DMBA was decreased, latent period of neoplasm development as well as the rate of tumor differentiation were increased and metastatic spreading into the regional lymph nodes was inhibited. PMID- 1298118 TI - [The effect of lipochromin on spontaneous carcinogenesis in mice]. AB - Development of spontaneous hepatomas was studied in CBA mice, which were maintained on a diet containing the carotenoid drug lipochromine in a dose of 25 mg/kg during their life beginning at the age of 3 months twice a week. Concentrations of vitamin A (as retinol) and beta-carotene were estimated in mice blood and liver tissue by means of HPLC. Decrease in occurrence of spontaneous tumors in liver tissue as well as distinct increase in periods of their development were detected in the animals treated with the drug. The phenomenon observed correlated positively with an increase in concentration of beta-carotene in liver tissue of tumor-bearing mice, thus indicating the preventive effect of lipochromine on spontaneous carcinogenesis in mice CBA strain. PMID- 1298119 TI - [The effect of carotenoids on rat stomach carcinogenesis, induced by N-methyl-N' nitro-N-nitrosoguanidine]. AB - The effect of natural carotenoids on gastric carcinogenesis induced by N-methyl N'-nitro-N-nitroguanidine (MNNG) was studied in 4 groups containing 105 rats. Highly carotenoid complex from wild rose fruits was added to drinking water of Group 1 (30 rats) at a dose of 15 mg/kg (as calculated per beta-carotene) 3 times weekly; as well as MNNG was present in water (0.01%). The carotenoid complex was supplemented to the ration 2 months before MNNG treatment and was continued within 15 months; MNNG treatment occurred within 6 months. Group 2 (30 rats) and Group 3 (30 rats) were treated with MNNG and the carotinoid complex, respectively; the 4 group (15 rats) was used as an intact control. Tumors were detected in 16 rats of 28 animals studied in Group 1 (57.1%) and in 11 rats of 25 animals in Group 2 (44%) (P < 0.05); malignization was found in the stomach and small intestine. The rate of involvement with gastric tumor in Group 1 was 3-fold higher as compared with those in the only MNNG treated animals--50% and 16%, respectively (P < 0.01). Tumors of the small intestine were detected in 5 rats of Group 1 (17.8%) and in 9 rats of Group 2 (36.6%); differences were statistically insignificant. However, carcinogenesis tended to accelerate. The mean time of stomach and small intestine tumor detection in Group 1 was equal to 286 and 276 +/- 46 days, respectively, and in Group 2--339.7 +/- 25.4 and 350.7 +/- 25.4 days, respectively (differences are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298120 TI - [The modified effect of carotenoids on rat forestomach carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine]. AB - A modifying effect of carotenoids on carcinogenesis induced by N-methyl-H'-nitro N-nitrosoguanidine (MNNG) in the rumen was studied in four groups of rats weighing 100-120 g. A diet of the first group contained a highly carotenoid complex from wild rose fruits at a dose of 30 mg/kg 3 times weekly; MNNG was administered at a dose of 5 mg per animal by means of a gastric tube for two days. Administration of the drug was repeated within 5 days. Treatment with the carotenoid complex was carried out 2 months before the MNNG administration. Group 2 and 3 received only MNNG or the carotenoid complex, respectively; Group 4 served as intact control. Tumors were detected in 33 rats of 81 animals studied (40.7%) in Group 1 and in 53 rats of 74 animals (71.6%) of Group 2 (P < 0.01). The mean time of the tumors detection constituted 40.7 +/- 9.5 days in Group I and 68.7 +/- 0.3 days (P < 0.05) in Group 2. All the tumors detected were localized in the rumen and consisted of papillomas appeared mainly as multiple forms. The data obtained suggest that carotenoids exhibited the modifying effect on MNNG-induced carcinogenesis of the rat rumen. PMID- 1298121 TI - [Antimutagenic properties of substances containing beta-carotene]. AB - Two carotene-containing drugs (natural and artificial) were shown to decrease the rate of chromosomal aberrations, induced by cyclophosphane, in bone marrow cells of mice, daily ration of which contained 10-20 mg/kg of beta-carotene within 1-3 weeks. The rate of chromosomal aberrations induced was decreased 1.5-2-fold in various experiments. Artificial beta-carotene exhibited aftereffect within at least 3 days, while its protective effect was decreased about by 20% within 7 days after administration. PMID- 1298122 TI - [Biological availability of beta-carotene]. PMID- 1298123 TI - [Immunopharmacokinetics of synthetic beta-carotene]. AB - The immunopharmacology and pharmacokinetics of synthetic beta-carotene were studied in complex clinico-laboratory investigations after single and repeated per os administrations of various doses of the drug to healthy volunteers and cancer patients. Repeated treatment with beta-carotene at a dose of 30 mg caused no significant changes in the immunological parameters studied. However, treatment with a dose of 250 mg altered the parameters as follows: alteration of beta-carotene content in blood, elevation of the counts of lymphocytes and T lymphocytes forming "active" rosettes, increase in the proliferative response of lymphocytes to the mitogen PWM and activation of natural killers. Single administration of the drug in a dose of 1,000 and 2,000 mg led to short-term reversible immunodepression, appeared as leukopenia, abolition of the proliferative response of lymphocytes to mitogens and inhibition of T suppressors. Kinetics of retinoids and beta-carotene content in blood plasma was studied after single per os administration of drug megadoses. PMID- 1298124 TI - [The effect of beta-carotene on interleukin-2 production and mitogen-induced proliferation of T-lymphocytes]. AB - Interleukin-2 (IL-2) production followed by with aftereffect of the immunosuppressive agent hydrocortisone and mitogen-induced proliferation of T lymphocytes were studied in the presence of artificial beta-carotene. Treatment of CBA mice with the drug was performed within various periods. beta-Carotene was found to elevate IL-2 secretion and the effect was both time- and dose-dependent. The drug removed immunosuppression developed after intraperitoneal administration of hydrocortisone. At the same time, beta-carotene stimulated mitogen-induced proliferation of T cells, which was dose-dependent. PMID- 1298125 TI - [Correction of primary and secondary immunodeficiency with synthetic beta carotene]. AB - Immunotropic activity of artificial beta-carotene was studied in primary immune response to thymus-dependent antigen (sheep erythrocytes) using models of primary (inherent) and acquired (vinblastine-induced) immunodeficiency. The experiments were carried out using two strains of CBA and C57Black mice with dissimilar responses to the antigen. beta-Carotene was found to remove both acquired and inherent immunodeficiency. The immunostimulating effect of the drug studied appears to be related to the activated production of mediators, namely IL-2. PMID- 1298126 TI - [The effect of beta-carotene on the dynamics of ornithine decarboxylase activity in atrophic mucous membranes and in stomach polyp tissue]. AB - Activity of ornithine decarboxylase was significantly increased, reaching the maximal values in malignant gastric tissues, in mucosal membrane and polypous tissue of patients with atrophic gastritis as compared with normalcy. Any alterations in the enzymatic activity were not observed in the gastric mucosal membrane of 19 patients with atrophic gastritis within 3 weeks. At the same time, statistically significant decrease of the abnormal high activity of ornithine decarboxylase was detected in atrophic gastric mucosal membrane of 12 patients among 20 patients examined, which were treated with 20 mg of beta-carotene daily within 3 weeks; the enzyme activity was decreased also in polypous tissue of 5 patients in the group of 9 patients studied. Decrease in the ornithine decarboxylase activity after beta-carotene treatment involved improvement of the mucosal membrane state, where hemorrhage disappeared and inflammation reduced. Since the high activity of ornithine decarboxylase is related to promotion of cancerogenesis, beta-carotene appears to exhibit an anticarcinogenic effect as it decreases the enzymatic activity in gastric mucosal membrane. PMID- 1298127 TI - [Potential cancer-protective effect of beta-carotene in experimental stomach carcinogenesis]. AB - Effect of beta-carotene on content of some metabolites of lipid peroxidation and activity of ornithine decarboxylase was studied in rat gastric mucosal membrane during gastric carcinogenesis developed after administration of N-methyl-N'-nitro N-nitrosoguanidine (MNNG). Intragastric administration of MNNG led to a significant increase in content of diene ketones and malonic dialdehyde in the gastric mucosal membrane within a day, while beta-carotene normalized or decreased considerably the MNNG produced accumulation of these lipid peroxidation products. In acute experiments with MNNG beta-carotene administered per os at a dose of 0.5 mg per animal did not affect the pronounced activation of ornithine decarboxylase in the gastric mucosal membrane. However, in chronic experiments with MNNG repeated administration of beta-carotene led to statistically significant decrease of the constitution-dependent enzymatic activation in the gastric mucosal membrane and to inhibition of locus formation with abnormally high activity of ornithine decarboxylase. The findings suggest that anticarcinogenic effect of the natural antioxidant beta-carotene was shown at the step of carcinogenesis promotion. PMID- 1298128 TI - [Modification of the body's resistance to acute ionizing radiation by synthetic beta-carotene]. AB - Radiomodifying efficiency of short-term and chronic medicinal and treatment prophylactic enrichment of rations with artificial beta-carotene, administered at single doses of 0.1-10.0 mg, were studied after acute external gamma-irradiation of adult nonlinear and Wistar rats (0.029 Gy/s) or female SBA mice (0.0037 Gy/s), where the absorbed dose was equal to 8-3 Gy or 9.9-9.5 Gy, respectively. Suspension of beta-carotene paste in olive oil accelerated death of rats irradiated at doses of 8 and 7 Gy (P = 0.04), and shortened their lifespan. At a dose of 6 Gy single and long-term enrichment of rations with beta-carotene decreased the rate of rat death within 30 days from 33.3% to 16.7% (P = 0.14) and 3.3% (P = 0.01), while their life time was increased from 48 days to 67 days (P = 0.05) and 508 days (P = 0.01). beta-Carotene was found to affect favourably the radiation-induced (5 Gy) leukocytopenia, and decreased thymus mass (6 Gy) and body weight (8 Gy). In treatment-prophylactic enrichment with beta-carotene of mice (9.9 Gy) ration their survival was increased from 15% to 30% and lifespan from 14.4 days to 28.9 days (P = 0.05). During medicinal or treatment prophylactic courses of beta-carotene death of mice (9.7 Gy) was decreased from 75% to 35% (P = 0.01) or 60% and life time was increased from 16.7 days to 22.17 days or 39.9 days (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298129 TI - [Creation of preventive-treatment substances based on carotenoids]. PMID- 1298130 TI - [Certain parameters of beta-carotene metabolism in the rat]. AB - Concentration of retinoids was decreased from 24.5 micrograms/100 ml to 13.5 micrograms/100 ml of blood serum in rats with ageing, during 2-11 months; these rats were maintained on a standard ration. Enrichment of rat ration with beta carotene caused a statistically significant increase in content of retinoids in blood serum from 24.5 micrograms/100 ml to 48.6 micrograms/100 ml within early periods (1-72 hrs), while within later periods (0.25-2 months) the retinoid content was similar to that of control intact animals. After single and, especially, in long-term treatments with beta-carotene dose-dependent deposition of the carotenoid and increase in content of retinoids were detected in liver tissue. Use of white rats is of importance in principle for evaluation of beta carotene caused modifications of pathological states developed under influence of unsuitable environmental factors. PMID- 1298132 TI - [Distribution of beta-carotene in the rat upon its intraperitoneal administration in water soluble and oil forms]. AB - Accumulation and excretion of beta-carotene in rat liver tissue were studied when the carotinoid was intraperitoneally administered as olive oil as suspension and a water liposomal suspension. Single injection of the liposomal form of beta carotene caused an increase in its content in liver tissue. If beta-carotene was administered at a dose of 10 mg/kg its maximal content 44 mg/g of the tissue was observed within one day, and at a dose of 50 mg/kg, its maximal content constituted 178 mg/g within two days. Administration of beta-carotene as an oil suspension at a dose of 50 mg/kg led to a considerably slight accumulation in rat liver tissue with the maximal value of 12 mg/kg of the tissue within two days. Possible use of beta-carotene various forms, as well as experimental models for study their biological activity are discussed. PMID- 1298131 TI - [The effect of administration of beta-carotene in an oil solution on its blood serum level and antioxidant status of patients with duodenal ulcer and erosive gastritis]. AB - Adequately good consumption of beta-carotene was observed in patients with duodenal ulcer and erosive gastritis after daily treatment with 18 mg of the carotinoid used as 0.1% oil solution: concentration of beta-carotene was increased approximately 3-fold in blood serum of these patients. Concentration of retinol was not increased in blood serum after treatment with beta-carotene, thus indicating that the drug treatment was not dangerous. Treatment with beta carotene led to improvement in the state of the antioxidative system of these patients as resistance of erythrocytes to peroxide hydrolysis was increased while content of malonic dialdehyde was decreased in blood serum. The carotene treatment contributed to arresting pain syndrome in patients with ulcers, to cicatrization of ulcers and to disappearance of gastric mucosal membrane erosion. PMID- 1298133 TI - [The effect of nitrogen-containing derivatives of 1,4-naphthoquinone on mitochondrial lipid peroxidation]. AB - Nitrogen-containing derivatives of 1,4-naphthoquinone synthesized in the form of donor-acceptor autocomplexes, may serve as highly effective antioxidative agents exhibiting their properties both in microheterogeneous medium (water-micellar Tween 80 solution) and in enzymatic and nonenzymatic oxidation of lipids in mitochondria. Some of these complexes studied, where intramolecular transfer of a charge occurred during nonenzymatic oxidation in mitochondria, were only slightly less effective in the antioxidant activity as compared with the standard antioxidant ionol. Distinct increase in the antioxidant activity of the most substances studied was detected in presence of reductases participating in mitochondrial chains of electron transfer and two of these drugs proved to be more effective as compared with menadione and ionol. The data obtained are of importance for pharmacological prognosis of these new biologically active substances efficiency. PMID- 1298134 TI - [Development of substances for active prevention of cancer based on vitamins and preventive-treatment products]. AB - The conception and program are described for development of drugs involved in active prophylaxis of malignant neoplasms. Development of prophylactic drugs and new treatment-prophylactic food-stuffs was shown to be possible and expedient to use toxic immunomodulators and natural anticarcinogens. Complex drugs are assumed to include carotenoids, tocopherols, water-soluble vitamins, polysaccharides and other biologically active substances exhibiting anticarcinogenic, antimutagenic and immunostimulating properties. New treatment-prophylactic food-stuffs are developed using milk protein concentrates, lyophylized cruciferous and vegetable juices and extracts of medicinal herbs. The work is realized in the research association involving academic, branch and educational institutions according to State priority programs. PMID- 1298135 TI - [Xenobiotic-metabolizing enzymes in rat liver and small intestinal mucosa with varying combinations of polyunsaturated omega-6 and omega-3 fatty acids in the diet]. AB - Male Wistar rats were fed for 30 days semi-synthetic diets containing lard, corn oil or fish oil (ichthynic oil from herring muscles), differing in total content of saturated and polyunsaturated fatty acids (PUFA), in the ratio omega 6/omega 3 PUFA and in content of vitamin E. The activity of xenobiotic metabolizing enzymes was similar in liver of rats fed diets with lard or corn oil, while activities of epoxide hydrolase and UDP-glucuronosyltransferase were significantly higher if fish oil was used. The type of fat affected also the benzyl-produced induction of the enzymes. Differences in the enzyme activities observed did not depend on content of vitamin E in dietary fats. Unlike liver tissue, activities of microsomal enzymes were not considerably altered in rat small intestine in various experimental groups. The microsomal lipids of liver tissue and small intestine mucosal membrane were similar in the total content of saturated and unsaturated fatty acids in various animal groups but the level of omega 6 and omega 3 PUFA in the tissues depended on the ratio omega 6/omega 3 PUFA in diets. PMID- 1298136 TI - [Possible reasons for bilirubin accumulation in the brain of newborn animals during oxygen deficiency]. AB - An increase in content of bilirubin was detected in brain tissue of newborn rats with chronic interrupted hypoxic hypoxia occurred during pre- and neonatal periods. Accumulation of bilidiene in animal brain tissues appears to occur due to the following causative factors: tissue acidosis, developed after oxygen deficiency, contributed to binding of bile pigment to brain cell plasma membranes, synaptosomal ones in particular; serum albumin lost its specific ability to bind bilirubin due to protein molecular accumulation of excessive fatty acids and acetaldehyde, which are bound to protein, as well as other minor ligands extracted by organic solvents. PMID- 1298137 TI - [Medical-biological aspects of carotenoids]. AB - The literature data involving 45 references are reviewed. Metabolism of carotenoids in human and animal tissues, distribution in tissues, antioxidative and immunomodulating activities of carotenoids, their anticarcinogenic properties are discussed. Use of remedial drugs containing beta-carotene holds much promise. PMID- 1298138 TI - [Intravascular ultrasound: a new dimension of invasive vascular diagnosis]. AB - Intravascular ultrasound is a new imaging modality which allows the visualization of the vessel wall in vivo and could thus become an important adjunct to conventional angiography. Using miniature high-frequency transducers mounted at the tip of flexible catheters, high-resolution cross-sectional images are created and displayed in real-time. Several investigations have shown good correlations between ultrasound and histologic or angiographic techniques for the measurement of cross-sectional dimensions. Atherosclerotic lesions can be characterized by their differences in echo-density as calcified, fibrous or lipoid. Initial clinical studies have demonstrated the possibility to detect acute changes, such as dissections, following PTCA and other interventions. Several potential clinical applications are being discussed, where intravascular ultrasound may yield valuable information in addition to that provided by angiography. If some important current limitations can be overcome, this method may add a new dimension to invasive vascular diagnostics. PMID- 1298139 TI - [Transesophageal echocardiography from the surgical viewpoint]. AB - Following the development of new techniques in echocardiography and especially of Doppler color flow imaging, a new dimension of cardiac surgery has been brought about. The use of transesophageal probes facilitates routine surgery to be performed without interferences and, also, comparability between repeated ultrasonic measurements. Originally, echocardiography was mainly applied for quality control by comparing pre- and postoperative echocardiograms. Now it is equally important in perioperative strategy planning guiding the surgeon's decision throughout the operation as well as in cardiac emergencies. Using intraoperative echocardiography routinely in cardiac surgery establishes a more and more close cooperation between surgeons, cardiologists, and anesthesiologists. In order to evaluate the clinical relevance of echo findings, they have to be repeatedly correlated to surgical realities and to long term results of clinical outcome. PMID- 1298140 TI - [Transcranial Doppler ultrasound in intensive care medicine]. AB - Transcranial Doppler sonography (TCD) enables measurement of blood flow velocities in the basal intracerebral vessels. The most important applications of TCD in the ICU are the diagnosis and monitoring of vasospasms caused by subarachnoid hemorrhage after rupture of an aneurysm. Further indications are the non invasive diagnosis of critical decreases of cerebral perfusion pressure, the evaluation of brain death and the monitoring of thrombolysis of occlusions of the middle cerebral artery. TCD lends itself as a valuable non invasive bedside monitoring tool, which enables continuous or intermittent monitoring of intracerebral hemodynamics without strain for the patients. Disadvantages to be mentioned are the dependence of experienced examiners and the long lasting training phase required to achieve the requisite experience. PMID- 1298141 TI - [The value of echocardiography in diagnosis of bacterial endocarditis]. AB - In recent years echocardiography has become the most important method for the diagnosis of bacterial endocarditis. Though identification of valve vegetations by M-mode echocardiography was rather limited, two dimensional echocardiography- especially with transoesophageal application--has a sensitivity of more than 90% and a specificity of 98%. In addition, echocardiography is able to supply valuable contributions for the evaluation of the patient's prognosis and in the identification of complications of infective endocarditis, such as: the extent of valve destruction, rupture of chordeae and other parts of the valves, as well as the presence of intramyocardial and paravalvular abscesses. In addition, the application of Doppler-echocardiography allows the semiquantitative evaluation of the degree of any valve insufficiency. PMID- 1298142 TI - [Nisoldipine in comparison with long-term nitrates]. AB - Nisoldipine represents a new attractive second generation calcium channel blocker of the dihydropyridine-class for the treatment of all types of coronary artery disease. The effect on chronic ischemia is comparable to long-acting nitrates, side-effects have been rarely observed. The advantages will be the high vascular selectivity with only slight negative inotropic effect as well as a long-lasting positive influence on the myocardial metabolism. Up to now, no studies have been reported which compare nisoldipine and long-acting nitrates directly, but this calcium antagonist appears to influence duration and intensity of symptomatic and silent episodes of ischemia similar to the nitrates. PMID- 1298144 TI - [Schmidt syndrome--a case report]. AB - Pathologic organ specific autoimmune disease frequently affect endocrine glands and mostly lead to an insufficiency of the organs involved. Immunoendocrine diseases often occur in a polyglandular fashion and are consequently termed autoimmune polyglandular syndromes or immunoendocrinopathy syndromes. Among the different types one of the most frequent is known as Schmidt's syndrome or typus tyreosuprarenalis. Two case reports typical for this syndrome are described from a clinical point of view indicating also the respective diagnostics. PMID- 1298143 TI - Efficacy, safety and tolerability of lovastatin and bezafibrate retard in patients with hypercholesterolemia. AB - Hyperlipidemia has turned out to be the most important risk factor for coronary heart disease and necessitates frequently lipid lowering long-term treatment. Therefore, efficacy and tolerability of hypolipemic drugs are of great interest. The objective of the present study was to compare the safety, tolerability and effect on plasma lipids of Lovastatin and Bezafibrate retard in patients with hypercholesterolemia. 99 patients with total cholesterol of > or = 250 mg/dl after a 4 week standard lipid-lowering diet were treated another 4 weeks with placebo and then randomized to 400 mg Bezafibrate retard or 20 to 80 mg Lovastatin given once a day for 12 weeks. Mean changes from baseline in total cholesterol, LDL cholesterol and triglycerides were significantly reduced, in HDL cholesterol increased in both treatment-groups (p < or = 0.01). The effects of Lovastatin on total cholesterol and LDL cholesterol were more pronounced than those of Bezafibrate retard (p < or = 0.01), while Bezafibrate had a larger effect on triglycerides (p < or = 0.05). The frequency of clinical adverse experiences was low and similar among treatment groups, the frequency of laboratory adverse experiences was higher in the Lovastatin group. One patient in the Bezafibrate group was withdrawn because of nausea, one patient in the Lovastatin group because of GGT elevation. PMID- 1298145 TI - [Vocal physiopathology]. AB - Cordectomies usually result in alteration of the glottic sphincter which in turn effects the activity of the entire larynx bringing about different types of dysphonia according to the resulting scarring pattern in the glottic floor and to the functional recompensation made by the cordectomized patients themselves. Today, study of those anatomic dynamics which determine voice typology in cordectomized patients is possible thanks to various means: synthesis of data obtained from psycho-perspective analyses of the vocal product, video-fiber laryngoscopic observation of the vocal tract and spectrographic study. The above mentioned examinations show how the type of dysphonia in these patients is determined by the various combinations of different scarring patterns, which also depend on the entity of surgical exeresis, and the position taken on by various laryngeal district during phonation? The authors present paradigmatic clinical cases in order to demonstrate the different phonatory capabilities achieved by patients who had undergone either cordectomy or cordectomy extended to the ventricle and false vocal cords. PMID- 1298146 TI - [The clinical presuppositions and results of logopedic therapy]. AB - Logopedic therapy is proposed in helping cordectomized patients learn to best use pneumo-phonal structures to compensate for the glottic insufficiency often resulting from this type of surgery. Rehabilitation showed be initiated as soon as possible following surgery before the patients starts using compensation mechanisms negative for voice quality. However, precisely those patients often receive therapy tardively when the anatomo-functional results have already been consolidated and the voice quality is poor. The rehabilitation discussed uses classical feed back mechanisms through which the subjects learn to recognise those factors which enable them to better their voice quality. The type of exercises to be employed depends on whether or cordectomy extended to the ventricle and to false vocal cord. On the farmer case, the principle aim of therapy is that of nearing the healthy vocal cord to the neocord through appropriate exercises. On the better case, instead, the main vocal compensation is the result of the perfect coordination of expiratory energy and the activity of the healthy vocal cord. In fact, in extended cordectomized patients, in the light of the modest amount of scarring, it is necessary to cause the healty voice cord to shift entirely towards and beyond the median line as to as compensate for a sphincteric loss. The authors report two clinical case, particularly difficult from a rehabilitation point of view, in which, relatively speaking, in light of the initial voice conditions, satisfactory results were obtained. PMID- 1298147 TI - [The use of Phonagel in glottic insufficiency]. AB - The authors describe their experience concerning collagen implantation in case of glottic insufficiency after cordectomy by the CO2 Laser. Three different kinds of injection are indicated as follows: injection of 3/4 of collagen in the site responding to vocal fold removal on 1/4 in the survival fold after cordectomy with conservation of the thyroarytenoid muscle; implantation of 1/2 in the new fold and 1/2 in the surviving one after cordectomy with removing of the cricoarytenoid muscle; infiltration of the whole material in the residual vocal fold after cordectomy enlarged to the false vocal fold and the ventricule as well. Video laryngoscopic and spectrographic examinations documented good phonatory results after collagen implantation in 19 cases over 21; two cases had a persisting insufficiency depending on the fact they had been previously operated of enlarged cordectomy and the scar tissue was not sufficient for measures and consistency to obtain a satisfactory injection of collagen. PMID- 1298148 TI - [Phonatory rehabilitation via esophageal voice and the laryngophone]. AB - Esophageal voice obtained through logopedic treatment and speech produced by electronic prostheses is the principal means of verbal communication of laryngectomized patients. Several factors condition the success of logopedic rehabilitation: entity of hypopharyngeal surgical exeresis and scar repairing modalities; rehabilitation technique employed; patient's skill in controlling pharyngo-esophageal tract and articulation organs; patient motivation. A previous study executed by our School reported that only the 20% of the patients who did not practise logopedic therapy employed the laryngophone. Reduced use of electronic prosthesis depends on three factors: acoustic products of poor quality; evidence of anatomic and functional impairment pointed out by laryngophone use; limitation of manual activity during phonation. Electronic prostheses have a precise indication in the following cases: immediately after surgery; in case of logopedic treatment failure and when tracheo-esophageal prosthesis are contraindicated; when the esophageal voice has an insufficient volume or in noisy environments. Finally indicative criteria to introduce patients to the most suitable rehabilitation modality are reported. PMID- 1298149 TI - [Tracheoesophageal prostheses]. AB - The AA. report their own experience in the field of tracheoesophageal speech rehabilitation of laryngectomees. In order to get a high rate of successful results, (an accurate selection of patients is of fundamental importance) mainly to identify the physical requirements and the motivational aspects potentially favouring vocal, rehabilitation. The personal technique of tracheoesophageal fistula creation under local anesthesia is illustrated, the procedure generally last 5-10 minutes with minimal tissue trauma and blood loss and is also suitable for outpatients. For the above-mentioned reasons, the AA. prefer to perform the tracheoesophageal puncture as a secondary procedure, i.e., after total laryngectomy, taking into account the many inconveniences related to primary rehabilitation, as reported in literature. Finally, advantages and inconveniences of the various types of prosthetic devices employed are illustrated and the causes of failure are discusses. PMID- 1298151 TI - [The restoration of the vocal possibilities for the laryngectomized patient with a tracheoesophageal prosthesis]. AB - The experience reported concerning vocal rehabilitation employing tracheoesophageal prostheses (TEP) in laryngectomized subjects at the University of Milan is based upon 149 patients who underwent procedures for total laryngectomy from November 1986 on in nearly all cases (137), a primary procedure was followed in order to insert a Blom Singer prosthesis. Some technical modifications in creating the fistula during the reconstruction phase of laryngectomy reduced the number of postoperative and local complications of the fistula. The men phoniatric rehabilitation time is 38 days from the procedure. The most important aspects affecting the length of rehabilitation are the presence of lower respiratory tract disorders and contemporaneous postoperative radiotherapy. The mean lifetime of the prostheses is 92 days, the main restricting factor being the care taken by the patient. Microbiological studies showed the virtually constant association between fungi and Pseudomonas sp. Nevertheless, infection of the fistula and forced removal of the prosthesis occurred only in 1 patient. Other complications were as follows: granulation tissue at the tracheal side of the fistula into the trachea or oesophagus, 6 and 1 respectively; enlargement of the fistula, 5; others, 15. Fifteen percent of the patients does not succeed in achieving a tracheoesophageal voice because of respiratory insufficiency, difficult neuromuscular control or psychological problems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298150 TI - [Esophageal voice: a critical analysis of the results obtained by different rehabilitative technics]. AB - In order to evaluate the phonatory results obtained with the use of tracheoesophageal prostheses, 38 laryngectomees were examined, 20 of which underwent erigmophonic voice rehabilitation while the other 18 were rehabilitated with the application of a prosthesis. In all cases electroglottography and spectrography of the voice were performed. In the erigmophonic-voice subjects, electroglottography gave a normal glottic wave while spectrography gave a tracing with frequent interruptions, scarce harmonics, altered by the presence of background noises. In the tracheoesophageal prosthesis patients, the electroglottogram showed regular hypopharynx vibratory activity while the spectrogram appeared free of interruptions activity while the spectrogram appeared free of interruptions and presented a uniform distributions and presented a uniform distribution of suffixes. The data obtained demonstrate that better results are obtained with the use of tracheoesophageal prosthesis as it allows the exhaled air to be used in phonation and thus respects respiratory dynamics and pneumophonic synergism. It also makes it possible to achieve a clear, fluent voice. Furthermore, the results obtained with patients with this prosthesis were constantly satisfactory when the long exercises required were performed. PMID- 1298152 TI - [The experience of early rehabilitation]. AB - Functional laryngectomies permit a more or less ideal preservation of laryngeal functions whose recovery, especially in les conservative operations, occurs very slowly and depends on several conditions: post operative course, sensitivity and motility of the hypopharynx, patient's ability to restore swallowing mechanisms. The Authors relate their experience concerning use of a rehabilitative program partially based on the experiences of some French logopedic schools and partially original. They illustrate the steps and goals of this program which starts on the fifth post-operative day with respiration exercises immediately followed by eight days of exercises to re-establish arytenoid mobilization and swallowing movements. If deglutition is not completely recovered and important inhalation problems persist, the logopedic approach is integrated with surgical rehabilitation consisting of one or more injection of gax-collagen. It is possible to use the same surgical technique later, after hospital discharge, if a slight dysphagia is still present in spite of continuous logopedic rehabilitation. Voice restoration exercises are introduced in the last days of the hospital stay when the patient is tube-free and continues at the office or outpatient clinic for two or three times every week. Concerning removal priority (tracheotomy tube followed by nasogastric tube or vice versa), we propose a diversified strategy for each patient, depending on the anatomicofunctional postoperative situation. Up to now 25 patients have taken part in this rehabilitation program (14 cricohyoidopexy, 6 Cricohyoidoepiglottopexy, 5 supraglottic laryngectomies). The results with regard to the amount of time that nasogastric feeding as well as tracheal tube are kept and the length of the hospital stay, were compared to those ones of a similar number of consecutive cases operated at our institution (ENT Department of Modena University) before February 1990 but not rehabilitated. In the early rehabilitated group, we observe a quicker functional recovery with a shorter hospital stay (about a week). PMID- 1298153 TI - [Functional recovery in subtotal laryngectomies]. AB - Subtotal laryngectomy, a valid treatment for carefully selected patients, is a safe oncologic procedure which preserves the cricoid-arytenoid unit creating a successful "neo-larynx" with valid phonatory and deglutition functions. At the E.N.T. Clinic of "La Sapienza" University of Rome from Jan. 1984 to Feb. 1992, 85 subjects underwent subtotal laryngectomy, 50 of which then underwent phoniatric examination. The remaining patients were not suitable candidates because of the trachealis cannula (14), or because they were lost at follow up (16). A total of 50 male subjects were examined. Twenty-eight underwent crico-hyoid-pexia, while 22 patients underwent crico-hyoid-epiglotto-pexia. Attention is drawn to the results which appear to be extremely variable with regard to each study group. We obtained better results with crico-hyoid-epiglotto-pexia than with crico-hyoid pexia and we guaranteed a good social re-insertion in all cases. PMID- 1298154 TI - [The diagnosis and treatment of dysphagia]. AB - The structures in the head and neck are important in respiration, deglutition and communication. The post surgical head and neck cancer patient will probably exhibit a variety of disorders in both speech and swallowing. This study examined swallowing problems in three groups of patients following ablative surgery for pharyngolaryngeal carcinoma: supraglottic laryngectomies, hemilaryngectomies and subtotal laryngectomies. A total of 28 patients were studied. Videofluoroscopic studies with liquid and thick paste were completed one week post initiation of oral feeding following surgery and during the rehabilitation treatment. PMID- 1298155 TI - [The definition of a reference protocol for the clinical study of vertigo drugs]. AB - The aim of this paper is to define the problems that arise in the clinical evaluation of drugs for the treatment of vertigo. Among these are the objective criteria used in defining vertigo and those used in evaluating efficacy of the drugs. The resulting protocol for a clinical study of vestibular drugs is a document that clarifies the debated points in the field, and above all furnishes guidelines for establishing uniformity in clinical studies. This, therefore, may become the reference protocol in Italy for clinical evaluations of drugs for the treatment of vertigo. PMID- 1298156 TI - [Facial nerve paralysis and mandibular fracture]. AB - The authors describe three cases of peripheral facial nerve paralysis in patients with a mandibular fracture. In two cases, in which the onset of palsy was uncertain, the facial nerve injury was contralateral to the fractured side. Topodiagnostic tests showed neural damage at the third intrapetrosal portion and at the genicular ganglion. In one of the two patients tomography revealed a fracture line through the anterio-superior wall of the external auditory canal homolateral to the facial palsy. In the third subject palsy set in immediately after the trauma and was ipsilateral to the mandibular fracture; the facial lesion was localized at the genicular ganglion. In the first two cases, functional recovery was spontaneous (40 and 0 days after the trauma respectively). In the third subject, the nerve was decompressed surgically with a complete functional recovery two months later. The functional and clinical findings of these three cases show that a contralateral facial palsy secondary to a mandibular fracture resolves spontaneously while the traumatic displacement of the mandibular condyle may determine a temporal bone fracture sometimes followed by a lesion in the intratemporal portion of the facial nerve. An event such as the latter may delay functional recovery and thus warrant surgery such as in cases of Bell's palsy. PMID- 1298157 TI - Bioavailability of methionine-hydroxy-analog free acid and S-methyl-methionine in the growing rat. AB - The biological utilization of DL-methionine (MET), DL-methionine-hydroxy-analog and DL-S-methyl-methionine-sulphonium-chloride (SMM) was tested in rat growth assay. Weight gain, feed efficiency, protein efficiency ratio (PER), net protein ratio (NPR) and net protein utilization (NPU) were applied as criteria. A test diet containing soybean meal as sole protein source was fortified with MET, MHA or SMM at 1.5 and 3.0 g/kg levels, respectively. All fortifications had a significant (p < 0.05) positive influence on weight gain, feed conversion and protein utilization. SMM showed the highest activity. MET and MHA were almost equally well utilized at 3.0 g/kg fortification level, however MHA proved slightly less efficient at 1.5 g/kg level than MET. PMID- 1298158 TI - Blood glutathione peroxidase enzyme activity as an index of selenium release from Permasel in ewes. AB - Ten Merino ewes were given a single Permasel pellet (containing 5% of elementary selenium) orally and examined for the release of selenium in the reticulum by determining glutathione enzyme activity of the whole blood haemolysate over a period of 12 months. As compared to the controls, the treated ewes exhibited a significant elevation in glutathione peroxidase activity for 8 months, indicating an acceptable persistence of the product tested. PMID- 1298159 TI - Improvement of the reproductive performance of sows by treatment with a GnRH superactive analogue. AB - The effect of a Hungarian-made superactive analogue of GnRH (Ovurelin, D-Phe6 GnRH-EA, Reanal, Hungary) on the postpartal sexual function of sows was monitored. GnRH treatment was carried out on day 19 before weaning. The sows were inseminated at the first oestrus after weaning. GnRH treatment markedly increased litter size at weaning, substantially reduced (to 25 and 50%, respectively) the number of sows failing to come into oestrus after weaning, and increased the number of sows coming into oestrus within one week after weaning by 42.5% and 9%, respectively. These beneficial effects were particularly apparent on the far using closed management technology. PMID- 1298160 TI - Serum progesterone, oestrone and oestradiol in pregnant and non-pregnant red deer hinds. AB - Changes in serum progesterone (P), oestrone (E1) and oestradiol (E2) concentrations were monitored in 34 female red deer (Cervus elaphus) shortly after the end of the breeding season and at mid-gestation. Pregnancy could be detected on the basis of serum P, but there were no significant differences between the pregnant and non-pregnant animals farmed animals in E1 and E2 concentrations. Twenty-five pregnant hinds captured in winter showed serum P levels similar to those found in farmed deer during the gestation period. PMID- 1298161 TI - Guidelines for the eradication of infectious bovine rhinotracheitis in Hungary. AB - The prevalence of infectious bovine rhinotracheitis (IBR) in Europe is reported. Possible methods are proposed for eradication of infection as well as for the maintenance and control of infection-free status. PMID- 1298162 TI - Paratuberculosis vaccine in a large dairy herd. AB - On a 500-cow dairy farm a total of 866 young calves less than one month old were vaccinated with a heat-killed oil-adjuvated bacterin against Mycobacterium paratuberculosis over a period of five years. The vaccinated calves were tested by faecal microscopy, bacteriology and serology on the day of vaccination, at the age of 3, 6, 9 and 12 months, at breeding age, and on the day of calving. A total of 721 bull calves and 379 female calves served as unvaccinated controls in two groups. The results were evaluated by trend analyses. Vaccination greatly reduced the faecal shedding of mycobacteria as demonstrated by the annual faecal microscopic examinations. During the last 6 months of the experiment only 9 of 612 samples were found positive by microscopy and by bacterial culture. The number of seropositive animals and the antibody titres demonstrated by the complement fixation test (CFT) and agar gel immunodiffusion (AGID) increased during the first three years. Later on, both the number of seropositive animals and CFT titres decreased. PMID- 1298163 TI - Ochratoxigenic moulds and ochratoxin A in forages and grain feeds. AB - The contamination of forages and grain feeds with ochratoxigenic moulds and ochratoxin A was examined. The investigations were carried out over a period of three years in all seasons. Feeds were found to be contaminated with moulds at a high level throughout the three research years. The highest percentage (95 to 100) of contaminated feed samples was noticed during the second year. Total viable counts of moulds established in 1 g of feed samples ranged from 0.5 to 7.8 x 10(6). Penicillium spp. were dominant in mycopopulations isolated from feeds. Ochratoxin-A producing moulds were present permanently. In the summer period of the second research year as much as 94% of the feed samples were contaminated by ochratoxigenic Penicillium species. P. verrucosum var. cyclopium P. verrucosum var. verrucosum, P. commune and P. chrysogenum, i.e. ochratoxin-producing moulds, were the most prevalent Penicillium species throughout the three-year investigation. Ochratoxin A was found in various feeds in all seasons, except in summer of the first research year. Concentrations of the toxin varied from traces to 400 micrograms/kg. It occurred consistently in the same types of feeds (hay, dried alfalfa, fresh alfalfa, concentrate, pelleted sugar beet pulp, corn silage). PMID- 1298164 TI - Sphaerospora infection of American catfishes (Ictalurus punctatus and I. nebulosus) in Europe. AB - The occurrence in Europe of a Sphaerospora species described in North America is reported. Based upon its morphological characteristics, the parasite could be identified with the species S. hankai described from brown bullhead in Canada. This parasite was found to infect channel catfish (Ictalurus punctatus) cultured in farm ponds in Italy and brown bullhead (Ictalurus nebulosus) living in the supply channels of fish ponds in Hungary. The spores and sporogonic developmental stages were situated in the lumen of the renal tubules. In the authors' opinion, S. ictaluri described from channel catfish can be considered synonymous with S. hankai. PMID- 1298165 TI - Early damages to lung capillaries in enzootic pneumonia of rabbits. AB - The present study is part of a series of investigations aimed at characterizing the "enzootic pneumonia" phenomenon in rabbits, both from the clinical epidemiological and the pathophysiological point of view. All affected rabbits included in this study showed an acute injury to pulmonary microvasculature, similar to changes reported in pulmonary infections caused by Gram-negative bacteria. Similar alterations were not found in the control rabbits. The clinical and morphological findings revealed certain similarities between the Enzootic Pneumonia Syndrome of rabbits and Adult Respiratory Distress Syndrome (ARDS) of man. Therefore, it is suggested that, just as in the human syndrome, heterophils (PMN) are directly involved in the pathogenesis of the process. Many of the similarities noted between the two syndromes would make it possible to postulate the natural disease in rabbits as an eventual animal model suitable for extrapolating data to humans. PMID- 1298166 TI - Teratological examination of the insecticide methyl-parathion (Wofatox 50 EC) on pheasant embryos. 2. Biochemical study. AB - Fertile pheasant's eggs were treated with the insecticide Wofatox 50 EC (50% methyl-parathion) by injection technique on day 12 of the hatching period. Treatment consisted of inoculation of 0.1 ml of different concentrations of the insecticide into the air space of embryonated eggs. The following dose levels were employed: 0.00, 1.35, 13.5 and 135.0 mg/kg egg of active ingredient. Biochemical changes in the plasma were evaluated by micro (photometric) methods which rendered possible the determination of several blood plasma variables of the embryos. At the highest dose level applied, serum alkaline phosphatase (SAP) enzyme activity and inorganic P concentration of the treated embryos showed statistically differences (reduction) as compared to the control data. Macroscopic alterations were detected at necropsy. PMID- 1298167 TI - Isolation of chicken anaemia virus from broiler chickens. AB - Chicken anaemia virus (CAV) infection was demonstrated, by both serology and virus isolation, in 1- to 6-week-old broiler chickens originated from various parent flocks in Hungary. Total losses in the broiler flocks were estimated at 7 to 8% and about 25% of the chickens failed to reach target body mass by the 7th week of life. The clinical signs, postmortem lesions and histopathological changes of the affected chickens were similar to those of naturally occurring CAV induced infectious anaemia of young chickens. In MDCC-MSB1 cell cultures, a chloroform-resistant virus smaller than 50 nm in diameter, resistant to heating at 70 degrees C for 30 min, and antigenically very closely related to the Cux-1 strain of CAV was isolated from the liver of naturally diseased broilers. This virus isolate was designated the Bia strain of CAV. Inoculation of susceptible 1 day-old SPF chicks with a CAV-positive liver extract from naturally diseased broilers caused pathological changes characteristic of CAV infection, namely impaired growth, severe anaemia with atrophy of the bone marrow, marked atrophy of the lymphoid organs and petechial haemorrhages throughout the body. A quite similar pathological syndrome was also induced by inoculation of 1-day-old SPF chicks with the MDCC-MSB1 cell-culture-propagated new Bia strain of CAV. The CAV was successfully reisolated from the livers of experimentally inoculated birds, and antibodies to the reference Cux-1 strain of CAV were also demonstrated by the indirect immunofluorescence test in sera of naturally diseased and experimentally inoculated chickens. No antibodies were found against infectious bursal disease virus, reticuloendotheliosis virus, Marek's disease herpesvirus as well as avian adenoviruses and reoviruses. The reported disease of young broiler chickens was associated with natural infection of a new isolate of CAV. On the basis of its physicochemical, antigenic and pathogenic characteristics, this virus is similar to other strains of CAV isolated from chickens in other countries. PMID- 1298168 TI - [Estimated biological markers of progression in human immunodeficiency virus infection]. AB - The biological markers for determining as early as possible the progression in the infection by the human immunodeficiency virus (HIV) are very important for the health care of patients, and to adapt their anti-retroviral treatment. Among those, four independent biological markers for predicting a pejorative evolution in the following 36 months are used in medical practice: two specific for HIV, p24 antigenemia and serum titre of antibodies to the p24 core antigen, and two non-HIV specific surrogate markers, the beta 2-microglobulinemia and the absolute number of CD4 T cell in blood. P24 antigenemia corresponds to an active retroviral in vivo replication. The cut off for detection is about 10 pg/ml. It is difficult to detect in black people, and in the asymptomatic or pauci symptomatic stages of the disease. The apparition or the increase of the serum p24 antigen levels suggest the occurrence of opportunistic infections. P24 antigenemia decreases or disappears during the treatment by zidovudine. The diminution or the disappearance of serum antibodies directed to the p24 core protein are secondary to the deficiency of the humoral immunity, and to an increase of the viral replication, which occur at the late stage of the disease. The diminution or the disappearance of serum antibodies to p24 precede the occurrence of AIDS by several months. The increase of the serum beta 2 microglobulin level is associated with the severity of the disease. In the San Francisco prospective cohort, the progression to AIDS in 36 months was 69% when beta 2-microglobulinemia was more than 5 mg/l, 33% when it was between 3.1 to 5 mg/l, and 12% when it was less than 3 mg/l. The beta 2-microglobulin intra-thecal synthesis level could serve as a marker for the specific HIV encephalitis. The CD4 lymphocyte count constitutes an independent provisional marker for progression to AIDS, probably the most important, but mainly of statistical value. A lymphocyte count of 200 CD4/mm3 is considered as the threshold of full blown AIDS. Beside these classic biological markers, numerous other parameters have been evaluated, without knowing their practical interest. Although the predictive markers for AIDS have a real statistical significance, their interpretation could be difficult or hazardous when applied to a sole individual. In a relatively short delay, the actual biological markers will probably be completed or changed, in the routine medical practice, by the use of direct virological markers evaluating the viral load (plasmatic or cellular viremia). PMID- 1298169 TI - A simple and rapid method for toxicological screening of 25 antidepressants in blood or urine using high performance liquid chromatography with diode-array detection. AB - A high performance liquid chromatographic method with diode-array detection (HPLC/DAD) for simultaneous screening of 25 antidepressants is presented. After single-step liquid-liquid extraction at pH9.5 using chloroform/2-propanol/n heptane (60/14/26, v/v), the substances are eluted on a Novapak C18 4-microns column (300 x 3.9 mm, id), with methanol/tetrahydrofuran/pH 2.6 phosphate buffer (65/5/30, v/v) as the mobile phase (flow rate 0.8 ml/min). Full UV spectra from 200 to 400 nm are recorded on-line during the entire analysis and may be automatically compared to spectra stored in a library. The analysis is performed in 14 min. The method is simple, rapid, and highly specific. PMID- 1298170 TI - Quantification of red blood cell fragmentation: usefulness of heating cells and of automatic counting devices. AB - Spontaneous red blood cell (RBC) fragmentation occurs in some membrane erythropathies like hereditary elliptocytosis (HE); this phenomenon is produced in normal RBC by heating at 49 degrees C, but not at temperatures below this limit; fragmentation is usually quantified by counting the number of fragments/1000 RBC under light microscopic examination. The present work demonstrates: i) that enumeration of fragments is performed more precisely with an automatic blood cells counter on the 'platelet' channel; and ii) that heating at 48 degrees C enhances the fragmentation of RBC when they have a severe disruption of skeletal lattice, like in HE. PMID- 1298171 TI - [Measurement of dihydropteridine reductase activity in dried blood eluates: physiological and pathological implications]. AB - Tetrahydrobiopterin deficiency in hyperphenylalaninemic babies has to be rapidly recognized since the disease requires a specific treatment. Although the measurement of pteridines in urine can detect most of tetrahydrobiopterin deficiencies, DHPR measurement has to be performed to circumvent the risk of missing DHPR deficiency, especially at the neonatal period. The possibility to measure DHPR activity in dried blood samples justifies itself by its convenience and simplicity. Expression of activity per mg of hemoglobin improves the precision of the assay by removing variation in the elution step (insufficient blood being loaded onto the filter paper, hematocrit variation, thickness of filter paper used). The distribution of DHPR activities, corrected from the progressive decrease with age, showed that 2.5% of the hyperphenylalaninemic or normal population have low levels of activity (below 50% of normal). This observation suggests that genetic variations may exist, as illustrated by the analysis of 11 families. Although blood DHPR measurement seems efficient for screening DHPR deficiency, the finding in a family of clinically normal subjects with zero activity illustrates the risk of false positive results of the enzymatic test. PMID- 1298172 TI - [Continuous training unit (MFC) 1992, 1. Unusual case of asthenia in a dentist. Case no. 1]. PMID- 1298173 TI - [Stage T1 malignant tumors of the arythenoid. Analysis of a series of 26 cases]. AB - 26 malignant tumours of the arytenoid classified as T1 according to the UICC 1987, were treated in the ENT and Cervico-Facial Surgery wards to Hospital Laennec between 1961 and 1990. The natural history of these lesions, locoregional efficiency of the different treatments used, the part played by chemotherapy, survival, causes of death and therapeutic modalities used as a last measure, have been analysed. The frequency of tumours with neuroendocrine has been emphasized. Such a diagnosis should be questioned when the initial biopsy does not diagnose a well differentiated epidermoid carcinoma. The use of argyrophil colouring in order to find neurosecretive granules helps in carrying out the diagnosis. The treatment of tumours, classed T1 N0 M0, of the arytenoid, is based on partial, laryngeal surgery associated with a preventive, jugulo-carotidian-ipsilateral ganglionary intervention. PMID- 1298175 TI - [Results of the treatment of aspergillosis of the maxillary sinus by exclusive middle meatotomy approach]. AB - Over a 3 year period the authors have managed 12 immune competent patients with aspergillosis of the maxillary sinus by intranasal sinus surgery using only a middle meatal approach. An enlarged middle meatal window was formed by resection of the superior surface of the inferior turbinate. especially designed curve suction tubes and forceps were used to reach all areas of the maxillary sinus in order to perform a macroscopically complete resection of all lesions. On no occasion Aspergillus was the alternative use of an inferior meatal window or a Caldwell-Luc approach necessary. The authors conclude that the use of a middle meatotomy for the surgical treatment of aspergillosis of the maxillary sinus makes it possible to assure complete resection, to adapt post-operative care and to permit prolonged aeration of the sinus. PMID- 1298174 TI - [Adjuvant chemotherapy in supraglottic epidermoid carcinoma stage T3]. AB - 92 squamous cell carcinomas of the supraglottic larynx classified as T3 were treated from 1977 through 1987 and retrospectively analyzed. All the patients of this series received chemotherapy as initial treatment (2 cycles). From 1977 through 1981 the combination of Vincristine-Methotrexate-Bleomycin (VMB) was employed; after 1981, the protocol: Cisplatinum-5 FU with or without Bleomycin (CF) was administered instead of VMB. All the patients were then surgically treated on the tumoral site and cervical lymph chains. At 5-year, there was no significative difference between the two chemotherapeutic regimen in term of locoregional recurrences and second primaries. 5-year actuarial survival rate was higher for patients treated with the CF protocol (71%) versus (54%) with the VMB regimen. Systemic metastases occurred less frequently after CF (4.5%) than after VMB (22.4%). These findings suggest that chemotherapy has substantially some activity against microscopic distant metastases. PMID- 1298177 TI - [Our experience of meatotomy in the treatment of paranasal sinus diseases]. AB - Results are presented of patients treated by endonasal microsurgery in the ORL clinic of the Lille UCH between January 1986 and July 1990. The principal affections treated were: chronic sinusitis, aspergillosis and Killian's polyp. The objective of the technique employed, which has evolved progressively, was in each case to eradicate the infectious focus or its cause, and to maintain satisfactory ventilation and drainage of the maxillary sinus. The technique used is described, and results presented based on the responses received from a questionnaire sent to 164 patients. PMID- 1298176 TI - [Inverted papilloma of the nose and paranasal sinuses. Apropos of 10 cases]. AB - Authors report a retrospective study of 10 new cases of inverted papilloma of the nose and paranasal sinuses, observed during a 26 years period, with a 6.1 years average follow up. This group is marked by 2 cases of directly carcinomatous association, 4 cases of recurrence and 2 cases of later malignant transformation. The responsibility of different types of human papillomavirus in the origin of this tumor and its malignant transformation is suspected. Preoperative evaluation is based on clinical examination, CT scan and endoscopic method while diagnosis and prognosis depend on histopathologic finding of the whole tumor. The aim of surgical treatment is the most complete removal of the tumor with as limited after effects as possible. Lateral rhinotomy is the most favoured surgical approach versus mid facial degloving and intranasal endoscopy. No surgical patient, no removal tumor, inadequate limits, malignant papilloma and early recurrence are indications for external radiotherapy. PMID- 1298178 TI - [Cholesteatoma and petro-mastoid excision. Indications and results apropos of 36 cases]. AB - An open operative technique was used in 36 (38%) of 95 patients with chronic cholesteatomatous otitis followed up by the same surgeon between 1986 and 1990. Although a good anatomical result was obtained in 88% of cases the functional result was less evident, since 57% of patients were left with a liminal tonal loss of less than 30 decibels. The reasons for using an open technique are analyzed, but in only 5% of cases could the possibility of using a closed technique be envisaged, making the classical discussion between open and closed methods of treatments of only academic interest. Petromastoidian evidement with reorganization of the cavity is considered to be effective therapy for cholesteatoma, but indications and technical procedures must be adhered to strictly. PMID- 1298179 TI - [Lower turbinectomy with endoscopic guidance. Mid-term results]. AB - The authors report about their experience with partial lower turbinectomy. Twenty nine cases were followed up over an average time lapse of 2 years. Anterior rhinomanometry was performed pre- and postoperatively in all patients. The results include 26 successful operations (90%) and 3 failures, one case of hemorrhage on pack removal and one of synechia. In view of the 3 failures, the authors are presently favorable to subtotal lower turbinectomy. PMID- 1298180 TI - [Treatment of simple snoring. Surgical pharyngoplasty vs. laser CO2 pharyngotomy]. AB - CO2 laser pharyngotomy is a newly described technique used in treatment bronchopathy without sleep apnea syndrome. Retrospective results of 70 CO2 laser pharyngotomies and 63 surgical pharyngoplasties are studied and compared. All patients were SAS free snoring patients. The results were rated satisfactory by 54% of the CO2 Laser treated patients against 78% for classical surgery. CO2 laser pharyngotomy is an easy procedure done in the office. The complication rate is very low. The predictive criteria upon which one can select the best procedure for each particular patient remain largely unknown. PMID- 1298182 TI - [Hirudin and hirudin fragments]. AB - Hirudin is a potent and specific thrombin inhibitor: compared with heparin thrombin inhibition occurs directly and does not require the presence of plasma cofactors. Recombinant hirudin is well tolerated in animals and in healthy volunteers. Its clearance half-life after IV administration range from 1 to 2 hours and its bioavailability after subcutaneous administration reaches 75%. In most of the experimental models the ratio of the haemorrhagic side effect against the antithrombotic efficacy is satisfactory. Hirudin analogs are mono or bivalent according to their recognition site on thrombin. Bivalent derivatives (Hirulogs) have been mostly evaluated: they exhibit pharmacologic properties similar experimental to that of recombinant hirudin and have been successfully used in several thrombosis models and in healthy volunteers. Taking into account these data the most appropriate use for hirudin and hirudin derivatives should be clinical situations where the role of thrombin is important or which are only partially controlled by heparin therapy. PMID- 1298181 TI - [Comparative study of cartilaginous and synthetic laryngotracheoplasty. An experimental study in rabbits]. AB - The most significant advance in the treatment of laryngotracheal stenosis in children is the augmentative laryngotracheoplasty using a graft of autologous rib cartilage (ARC). In order to reduce the potential morbidity of this technique due to the additional surgical procedure, the use of a ceramic, hydroxyapatite (HA), implant was compared to ARC in a randomized experimental study in 99 New Zealand rabbits: 32 rabbits had ARC grafts, 33 had HA implants covered with a graft of perichondrium (HAP) and 33 had naked HA implants. At 3 months, immediately before necropsy, there was no significant clinical difference between the 3 groups of animals. Histological examination was performed in 81 animals. Implants were found in 54 specimens. More implants were found in the ARC group than in the HA groups (p < 0.003). No difference was noted between the 3 groups in the epithelial covering of the implant, the amount of inflammation, the analysis of the interface between the implant and the cricoid cartilage and in the viability of the graft. No implant was found in 27 animals. However, scar bands of approximately the same width as the implant were responsible for cricoid diastasis in 23 cases. Therefore, it seems that the missing implant played the role of spacer. While this experimental study does not eliminate HA as a augmentative implant in the subglottic region of the rabbit, the evolution of the scar bans must be followed for a longer period in rabbits before considering the clinical application of this technique. PMID- 1298183 TI - [Complementary value of the isoprenaline test and high-amplification ECG in the diagnosis of arrhythmogenic dysplasia of the right ventricle]. AB - Arrhythmogenic dysplasia of the right ventricle is a common cause of ventricular arrhythmia. It is important to reach a diagnosis, due to the risk of sudden death, particularly as this may be the first sign of the disease. Diagnosis is based on the angiographic demonstration of a morphological or structural abnormality of the right ventricle, and non-invasive tests are relatively insensitive. From a case investigated in 1984, the authors carried out a prospective determination of the diagnostic value of the isoprenaline test in 61 patients suffering from arrhythmogenic dysplasia of the right dysplasia confirmed by angiography. High concentrations (8-30 micrograms/min) of isoprenaline were continuously infused over a period of 3 minutes, regardless of the heart rate achieved. In a control group of 50 subjects with no myocardial disorder, isoprenaline induced monomorphic wave-burst arrhythmia in only one patient (2%). In the subjects affected by right ventricular arrhythmogenic dysplasia, isoprenaline induced one or more episodes of wave-burst ventricular arrhythmia in 52 patients (85%): one triplet in four patients, several episodes of wave-burst arrhythmia in 31 patients and prolonged ventricular tachycardia in 17 patients. Polymorphic arrhythmia occurred in 80% of cases, but left lag forms predominated. High-amplification ECG demonstrated late potentials in 66% of cases, i.e. in 80 and 62% of patients with and without prolonged VT respectively. The isoprenaline test or high-amplification ECG gave abnormal results in 58 of the 61 patients, with a cumulative sensitivity of 95 percent. PMID- 1298184 TI - [Polyaneurysmal dystrophy (ectatic medial dystrophy)]. AB - Polyaneurysmal dystrophy is a novel form of arteriopathy which specific clinical, angiographic, anatomic and surgical features which distinguish it clearly from multiple atheromasclerotic aneurysm. It should be considered to be a local, multifocal accentuation of megadolicho-arteries, which constitute the lesions during the early stages of the disorder (fairly general elongation of the elastic arteries, with thin walls and regular increase in the caliber and multiple tortuousness). Arterial angiography identifies polyaneurysmal dystrophy; in the context of a twisted and sinuous system of large arteries, multiple spindle shaped aneurysms can be distinguished which are frequently bilateral and symmetrical. The usual sites are the trunks of the aortic group and internal carotid, the ileo-femoral trunks and terminal aorta. The progress of the disorder is characterized by the possibility of rupture or thrombosis (particularly in the subcrural territory). The treatment is always surgical. The indication for surgery is inevitable in cases of severe ectasia, but may be avoidable in extensive forms of megadolicho-arteries with no clearly defined aneurysm: annual ultrasound monitoring is then called for. The disorder is of constitutional origin (and totally unrelated to atherosclerosis). Delayed dilatation of the aneurysms is due to the hemodynamic forces brought to bear on the fragile walls over a life-time. Multiple aneurysms occur mainly between the ages of 50 and 70 years, with a predominance of aorto-ileac sites in men, even though these subjects do not show any general elastic dysplasia. Half of the 45 patient undergoing surgery were hypertensive. PMID- 1298185 TI - [Effects of disopyramide on normal and pathological atrioventricular conduction]. AB - Disopyramide is a Vaughan-Williams class Ia antiarrhythmic, which is distinguished by its anticholinergic activity, which is due to its active metabolite: mono-N-alkyl disopyramide. In cells with a rapid response, such as those in the His-Purkinje tissue, it depresses conduction. In slow-responding cells (sinus node and Tawara's node) direct depression of conduction and automatism, and anticholinergic stimulation have opposing effects. In terms of clinical electrophysiology, this is a Touboul class IIa compound: and action mainly on the His-Purkinje system involving extension of the conduction time and of the refractory time. Nodal conduction is improved according to measurement of the alternate Wenckebach; according to studies of the denervated heart in transplanted patients, there is a depressant effect on automatism and conduction at all levels, but the vagolytic effect corrects this activity at Tawara's node. Clinical trials have demonstrated the absence of any deterioration, and in some cases and actual improvement of nodal conduction disorders in response to disopyramide and good safety in the presence of non-major intraventricular conduction problems (such as bundle branch block). In practice, these properties mean that moderate nodal conductive disorders and simple bundle branch block do not constitute an obstacle to the use of disopyramide. In junctional tachycardia, it is particularly indicated for use in tachycardia involving an accessory pathway, but is also effective in intranodal tachycardia due to its twofold action. PMID- 1298186 TI - [Acute hemodynamic effects of SIN-1 and isosorbide dinitrate in stable left ventricular failure: a comparative double-blind, cross-over study]. AB - The acute hemodynamic effects of intravenous SIN-1 (1 mg) and sublingual isosorbide dinitrate (5 mg) were investigated in 12 patients (8 men and 4 women) between 38 and 80 years of age and suffering from stable chronic left ventricular failure (NYHA Classes III-IV) secondary to ischemic myocardiopathy (n = 5), hypertensive disease (n = 2) or idiopathic disorder (n = 5) corresponding to the following hemodynamic inclusion criteria: stable condition, cardiac index > or = 2 l/min/m2, mean capillary pressure > or = 18 mmHg and < or = 28 mmHg. Previous treatments were continued with the exception of vasodilators and diuretics which were stopped 24 hours earlier. The hemodynamic data from this cross-over, double blind double-dummy trial were collected for two 60-hour periods separated by a washout period of 120 minutes. Simultaneously, venous samples were taken for the assay of plasma levels of SIN-1. The heart rate, cardiac output, pulmonary artery resistance and blood pressure were not affected by either SIN-1 or isosorbide dinitrate. An obvious reduction (> 15% of the basal value) in the mean capillary pressure, pulmonary artery pressure and mean right atrial pressure was observed in 10 subjects after SIN-1 and in 7 patients isosorbide dinitrate. A statistically non-significant trend towards a more marked effect (number of patients responding and maximum amplitude of pressure reduction) which occurred more rapidly and lasted longer was observed after SIN-1. Analysis of the relationship between the pharmacodynamics and pharmacokinetics of SIN-1 suggests that an active metabolites is involved. No adverse effects were reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298187 TI - [Echocardiographic myocardial performance in the normal postpartum in black African women]. AB - The authors have carried out a prospective ultrasound study of normal post-partum myocardial performance in black African women free from any systemic and/or cardiovascular disorder. The volume overload, reduction in ejection indices and increase in telesystolic constraint, which are significant essential changes observed immediately post-partum, return to normal values within two months. According to the authors, these disturbances reflect a transient change in myocardial function which expresses the potentially harmful effect of the natural changes during the normal post-partum phase. PMID- 1298188 TI - [Determination of the anaerobic threshold in chronic cardiac failure. Value and limitations]. AB - Anaerobic threshold was studied in 35 patients with cardiac failure present for more than 6 months, of primary or ischemic origin and New York Heart Association Stage II or III. Each patient underwent an exercise test of ergometric bicycle (increments of 10 watts/1 minute) with analysis of expired gases respiratory cycle by respiratory cycle (oxygen consumption, carbon dioxide production, respiratory oxygen and carbon dioxide equivalent, respiratory quotient). Anaerobic threshold was determined indirectly following Wasserman's recommendations. It was possible to determine anaerobic threshold in 25 patients (83.3%). The test was well tolerated. The two best methods for detection of anaerobic threshold were divergence of the curve of production of carbon dioxide in relation to oxygen consumption and an increase in respiratory oxygen equivalent while the carbon dioxide equivalent remained constant. In addition, oxygen consumption at the anaerobic threshold was statistically correlated with functional class (p < 0.05) and with the Weber classification based upon peak oxygen consumption (p < 0.001). Finally, anaerobic threshold occurred on average at 5.4 +/- 1.8 min from the start of exercise with a heart rate of 119.7 +/- 18 bpm, an oxygen consumption of 10.5 +/- 2.3 ml/min/kg (i.e. 43.2 +/- 12.1% of maximum oxygen consumption and 70.5 +/- 19.3% of oxygen consumption limited by symptoms) and a respiratory quotient of 1.07 +/- 0.08. In conclusion, analysis of respiratory gases during exercise in cardiac failure patients enables, with sub maximal exercise and noninvasively, the determination in the majority of cases of anaerobic threshold, which is statistically correlated with New York Heart Association stage and the Weber classification based upon oxygen consumption at peak effort. PMID- 1298189 TI - [Thrombolysis and massive pulmonary embolism: occasionally spectacular results]. AB - The authors report the clinical history of a 47-year-old patient hospitalised as an emergency with acute respiratory distress complicated by cardiocirculatory arrest. The diagnosis of pulmonary embolism was rapidly suspected and confirmed by emergency pulmonary angiography. A definite diagnosis enabled the early prescription of fibrinolytic treatment in situ. The interest of this case lies essentially in demonstration of the efficacy of fibrinolytic treatment which enabled the rapid restoration of a stable hemodynamic status and normalisation of angiographic appearances within a few days. PMID- 1298190 TI - [Spontaneous idiopathic pneumopericardium in young patients. Review of the literature. Apropos of a new case]. AB - Spontaneous idiopathic pneumopericardium (SIPP) in young subjects is a rare disorder since, apart from the case described here, only 28 cases have been reported in the literature. It occurs mainly in young adults. The physiopathology of the disorder involves alveolar rupture, as described by Macklin. The symptoms of SIPP are dominated by chest pain, which usually develops suddenly and is combined with dyspnea. Clinical examination is not very helpful, cardiac auscultation detects either pericardial rubbing or a more suggestive metallic sound. Recovery usually occurs without treatment, but there is a risk of long term recurrence. An unusual complication to be feared is aerial tamponade, which may be life-threatening and calls for emergency draining. The treatment of SIPP involves strict bed-rest, symptomatic treatment of the pain and clinical monitoring. PMID- 1298191 TI - [Ergotism and ischemia of the limbs]. AB - Clinical ergotism as seen today results almost exclusively from the intake of ergotamine tartrate in the treatment of migraine headache. Vasospasm of peripheral arteries is the leading clinical picture. Besides the formation of collaterals and a secondary thrombosis, the vasospasm is one of the specific findings in arteriography. Early diagnosis and withdrawal of the medication makes complete restitution possible. In all other cases intraarterial or intravenous infusion of sodium nitroprusside has turned out to be the most effective therapy. Balloon dilatation or operative intervention are an alternative therapy in those cases, where amputation of the limbs seems to be necessary. PMID- 1298192 TI - [Preventive drug therapy of recurrence of atrial fibrillation]. AB - Without treatment, about 60% of atrial arrhythmia patients suffer a relapse within 3 months and 70% within one year. Antiarrhythmic treatment intended to reduce this percentage is therefore justified, on condition that it is well tolerated. Several preliminary questions have to be settled before this medical prophylaxis: 1) Justification of antiarrhythmic treatment (sometimes pointless to deal with very occasional episodes); 2) Treatment of the underlying heart disease (valve disease, cardiothyrotoxicosis, etc.) or promoting factors (potassium depletion etc.); 3) Accurate assessment of any associated conduction abnormalities, which may constitute a contraindication to antiarrhythmic treatment (WPW syndrome in the case of verapamil and the digitalis-like drugs) or require additional treatment (pacemaker); 4) Definition of the mechanism (vagal or sympathotonic) inducing arrhythmia; 5) Evaluation of the hemodynamic parameters of the underlying heart disease (size of the atria, ventricular function, coronary or valvular lesions) which may limit the efficacy of the treatment. Once these parameters have been identified, the primary treatment should be type la or lb antiarrhythmics, which have been shown to be effective, despite the fact that they are not without arrhythmic risks (the Ib antiarrhythmics are less effective and have a poor safety profile). The beta blockers have preferential indications (hypersympatheticotonia, hyperthyroidism, hypertrophic myocardiopathy, mitral prolapse, angina etc.) and can be replaced by verapamil or bepridil if there are non-cardiac contraindications (ulcers, asthma, diabetes). Amiodarone is extremely effective, but its poor extracardiac safety restricts its long-term use. Complementary treatments (digitalis-like, anticoagulants or anti-PAF and cardiostimulant drugs) should be added if necessary. Recurrences (to be confirmed by ECG or Holter) should lead to rigorous confirmation of therapeutic compliance and observance of simple hygienic and dietary measures (no excessive exertion, elimination of stimulants etc.). With strict clinical and ECG monitoring, it would then be possible either to increase the dose levels (accompanied by plasma determinations if possible) or to switch to a treatment with more effective, but more aggressive drugs (amiodarone, flecainide) or to use drug associations (la and lb, la and II etc.). Repeated failure of such attempts should lead to a non-medical approach to treatment. PMID- 1298193 TI - [Hemodynamic study of intravenous milrinone in 26 patients with NYHA class III or IV cardiac failure]. AB - The hemodynamic effects of milrinone (WIN 47203) were studied in 26 NYHA Class III or IV patients. The compound was administered intravenously using a protocol including an initial push dose of 50 micrograms/kg in 10 min, followed by a 24 hour infusion at the dose of 0.5 microgram/kg/min. Maximal response was obtained after 15 min and persisted during the infusion: cardiac index increased from 2.08 +/- 0.36 l/min/m2 to 3.09 +/- 0.68 l/min/m2, while capillary pressure fell from 25 mmHg to 16-17 mmHg. These variations were significant (p = 0.01). Heart rate was stable. Mean peripheral blood pressure fell modestly (6%). Systemic vascular resistance fell by 30% and pulmonary vascular resistance by 20%. All these results confirmed the beneficial effect of this inotropic agent administered intravenously. The increase in ventricular premature contractions noted by many justifies the careful surveillance of these patients by monitoring. PMID- 1298194 TI - Light and electron microscopic study of vestibular sensory epithelia in 17 cases with acoustic neurinoma. AB - Vestibular sensory epithelia were studied histologically and ultrastructurally in 17 cases with acoustic neurinoma (AN). The superior vestibular nerve (SVN) near the fundus was also histologically studied in 5 of these 17 cases. Histologically, severe fibrotic change of the vestibular sensory epithelia was found in 1 case, and severe fibrotic change of the SVN was also found in this case. Intra-epithelial cysts were found at the edge of the utricular sensory epithelia in 2 cases. The cysts consisted of the transitional epithelium and were filled with the darkly stained substances. Ultrastructurally, abnormal accumulation of darkly stained masses within the nerve ending and abnormal accumulation of the fibrillar material below the normal basal lamina were frequently observed. These morphological changes described above were regarded as the pathological changes due to AN. In addition, the relationship among the histologic changes, ultrastructural changes and clinical data were fully investigated, and some histologic and ultrastructural changes were regarded as artifacts or age-related changes. PMID- 1298195 TI - A case of congenital ossicular malformation with mild auricular deformity: embryological and surgical considerations. AB - A case of bilateral congenital conductive deafness with mild auricular deformity is presented, and the anomalous structure deformity of the ossicles was multi focal in this case, and a previous report indicates that ossicular malformation in the ear with congenital conductive deafness is multi-focal when the external ear is only slightly deformed. Bilateral ossicular reconstruction with replacement of the stapes yielded satisfactory results. PMID- 1298196 TI - Intratemporal facial nerve neurinoma without facial paralysis. AB - A 38-year-old man was referred by his general practitioner to our department on 28 October 1991, with a 2-week history of vertigo. A left aural polyp was identified. The audiogram showed a moderate conductive loss on the left side. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the expanding lesion in the descending portion of the facial nerve. However, there was no seventh nerve paresis. At operation, the neurinoma (Schwannoma) filled the middle ear cleft and extended from the genu to the stylomastoid foramen. The floor of the middle ear had been eroded, exposing the jugular bulb. Facial nerve paresis is the usual presenting feature of a facial neurinoma. The case is presented for the reason that the absence of facial palsy as a presenting feature is rather rare, especially in the cases with large tumor and extensive bone erosion. PMID- 1298197 TI - Immunohistochemical detection of serous cells in nasal mucosa with monoclonal antibody against a component in human nasal secretion. AB - Secreting mechanisms of secretory cells in nasal mucosa and the changes of nasal secretions in chronic inflammatory sinusitis have been studied by the biochemical and histochemical methods. These methods could not clarify the changes of quality and quantity of nasal secretions and secretory cells. In order to obtain the specific marker for the secretions in different cells, we have produced monoclonal antibodies against a component in human nasal discharge. One antibody was selected for further characterization, because it stained submucosal serous cells specifically. This antibody stained the components of serous cells with molecular weight of 14 kD specifically, and was sensitive to periodate oxidation treatment. This antibody will be useful for detecting the subpopulation in secretory cells of human nasal mucosa, and may be serve as a biochemical probe for secretory activity of particular secretory cell types. PMID- 1298198 TI - Evaluation of provocation tests in tonsillogenic focal infection from the standpoint of fibrinolytic activity. AB - In this paper, we carried out provocation tests by means of ultra-short wave stimulation in patients with focal infection including palmoplantar pustulosis and examined the changes in fibrinolytic activity of the circulating blood. In the positive group with palmoplantar pustulosis, the t-PA level was slightly increased after the provocation and the FDP level in the positive group was increased. On the other hand, the AT-III activity in the positive group with palmoplantar pustulosis was decreased and the antiplasmin activity in the positive group was increased. The changes of antiplasmin activity observed in this experiment did not correspond with the pathophysiological explanation of an increased fibrinolytic activity in the circulating blood. It was suggested that a positive provocation test is accompanied by an increase in fibrinolytic activity in the circulating blood of patients with focal infection of the tonsil, and the increase in fibrinolytic activity is closely related to the positiveness of the provocation test. PMID- 1298199 TI - Electron microscopic study of vascular regeneration in rat tracheal mucosa following physical curettage. AB - Transmission and scanning electron microscopic studies were made of regeneration of the vascular network of rat tracheal mucosa on 30 min to 8 hr after the mechanical curettage. The vascular network casts were made by infusion of Mercox resin through the aortic arch for scanning electron microscopy. At 30 min after curettage, vascular thromboses were observed, and terminal blind branches were formed in the injured blood vessels areas through SEM observation. Diapedesis of leukocytes appeared at 30 min after curettage from intact venules at the wound margins. Recovery from the loss of endothelial cells began at 30 min after curettage. At 3 hr after curettage, vascular indentation (protrusion) and vascular process (bud-like process) were developed from intact venules at the wound margins. It is concluded that the formation of thrombus and terminal blind branch vessels constitute the initial reparative reactions of the injured vascular network and that new vessels then begin to form by outgrowth of protrusions and bud-like processes from intact venules at the wound margins. PMID- 1298201 TI - Nasal ciliary motility in retinitis pigmentosa. AB - Normal in-vitro ciliary beat frequency is reported in a patient with retinitis pigmentosa. The significance of electromicroscopic ciliary defects in this condition is appraised. PMID- 1298200 TI - Tuberculosis of the parotid salivary gland. AB - An interesting and rare case of tuberculosis involving a parotid gland is discussed. Although pulmonary tuberculosis is not uncommon in Turkey, primary parotid gland involvement is rare. The patient was treated by parotidectomy and antituberculous chemotherapy. PMID- 1298202 TI - Haemagglutination-inhibition technique for definitive diagnosis of rinderpest virus-specific antibody. AB - A simple and rapid serological method for the definitive diagnosis of rinderpest specific antibody is described. The technique is based on adsorbing out the cross reacting antibodies to peste des petits ruminants antigens from a rinderpest immune serum, thereby leaving active the specific antibody to rinderpest which is determined by haemagglutination-inhibition test. PMID- 1298203 TI - Typical repeat breeding and its improvement in buffaloes. AB - Propagation problems in buffaloes are often not easily recognizable, particularly lacking are studies on the repeat breeding syndrome. In the present study repeat breeder buffaloes were inseminated 3 or more times within the same lactation period. The incidence of typical repeat breeders was 8.33% in the lactation herd. These animals had a longer lactation period and a higher number of services per conception than normal buffaloes. The correlation coefficients were significant between the number of services per conception and each of weight at birth and weight at first service. Repeat breeders significantly (P < 0.05) surpassed normal buffaloes in creatinine values and had contrary values in the serum albumin concentration, glucose, inorganic phosphate, and zinc. Progesterone in urine (efficacious progesterone) was significantly lower on the 10th day post estrus, whereas the non-efficacious progesterone was significantly higher in repeat breeders. Supplying the repeat breeders with sodium phosphate for 1 month 40 g/head/day in the diet and 500 ppm zinc acetate in the drinking water improved the conception rate by 80%. PMID- 1298204 TI - Medical examination for health of all athletes replacing the need for gender verification in international sports. The International Amateur Athletic Federation Plan. PMID- 1298205 TI - Chronic fatigue syndrome: a joint paediatric-psychiatric approach. PMID- 1298206 TI - Infection of proplast malar implants following dental injections. AB - Two cases of late infections of malar implants are reported following dental work. Inadvertent inoculation of the implants by mouth organisms during injections for local dental anesthesia is implicated as the causative factor. Patients should warn their dentists that a malar alloplast has been inserted. Alternative techniques of maxillary dental anesthesia should be entertained, and antibiotic prophylaxis should be considered. PMID- 1298207 TI - Accidental injuries and blood exposure to cardiothoracic surgical teams. AB - A survey was undertaken over a 15-week period (62 working days) to find out the incidence and common mechanism of accidental injuries and blood exposure in cardiothoracic surgical teams. Two hundred and seventy events were reported: 70% glove penetrations, 18% skin punctures, 4% non-bleeding skin lesions and 8% lacerations with bleeding. Eye splashes occurred in 14% of the cases. The risk to the team was higher for cardiac surgery (1.6) than for thoracic surgery (0.5) and endoscopy (0.01). Most of the events were self-inflicted by experienced personnel. The surgeon's left index finger was most frequently injured, and the majority of the injuries were caused by needles followed by wire injuries during sternal closure. Prevention should be directed towards a safer technique for sternal closure, and protection of the surgeon's hands, especially his left index finger, should be found. Eye protection with goggles should become routine. This study demonstrates that open heart procedures carry a high risk of injury and frequent exposure to blood increasing the risk to the surgical team of acquiring viral infections (hepatitis-B and HIV) from the patients. PMID- 1298208 TI - Praxilene (naftidrofuryl oxalate) as an alternative for the augmentation of femoro-distal bypass blood flow. AB - In 30 patients undergoing femoro-distal bypass the effect of papaverine and praxilene on blood flow in the graft was measured. The mean resting flow was 129 ml min-1 (range: 91-167) and after papaverine was 202 ml min-1 (142-262) and after praxilene was 205 ml min-1 (143-267). Praxilene has a similar effect to papaverine in the augmentation of blood flow, and further investigation is needed to see if long-term praxilene administration might improve graft survival. PMID- 1298209 TI - A new infiltration needle for rapid local anesthesia in retromammary breast augmentation. AB - In the past, local field block anesthesia for retromammary breast augmentation has usually been performed with spinal needles. In this article, I present an alternative, a cannula-like needle that delivers large amounts of very dilute local anesthetic in an extremely quick fashion for retromammary breast augmentation. Besides being a time-saver, this needle also offers the patient better anesthesia and improved safety. Another advantage is that the retromammary pocket is partially hydrodissected by the large amount of dilute anesthesia delivered, thereby further decreasing intraoperative time. A description of the instrument, its usage, and its pros and cons are given. PMID- 1298210 TI - Buying human organs--evidence that money doesn't change everything. PMID- 1298211 TI - Systems versus performance problems: a peer review organization's perspective. AB - An analysis of Ohio's Medicare data base by the state's Peer Review Organization, using the most common diagnosis-related group in the Medicare population (heart failure and shock), from January 1, 1989 to January 1, 1991, identified 72 cases with confirmed quality-of-care problems. The analysis was performed to determine whether the majority of quality-of-care problems are related to systems or performance deficiencies. Study results indicated that health care workers are being inappropriately blamed for problems that are inherent in the health care system--74% of problems were related to inefficiencies in the health care delivery system, and 26% were determined to reflect performance problems. PMID- 1298212 TI - Total quality management. PMID- 1298213 TI - Standardized medication administration times solve pharmacy and nursing problems. PMID- 1298214 TI - Future relationships of dentistry and medicine in education and practice. PMID- 1298215 TI - Oral cancer--time for some home truths? PMID- 1298216 TI - Beta-endorphin concentrations in the peripheral blood mononuclear cells of migraine and tension-type headache patients. AB - Levels of beta-endorphin in peripheral blood mononuclear cells have been studied as a new approach to investigating opioid tone in migraine and tension-type headache. Sixty-one patients with migraine without aura, 39 with migraine with aura and 23 with episodic tension-type headache were compared with 37 healthy controls. Peripheral blood samples were taken from patients not enduring headache attacks and not undergoing prophylactic treatment. A significant reduction in peripheral blood mononuclear cell beta-endorphin concentrations was observed in migraine patients with and without aura, but not in tension-type headache patients. Altered transmitter modulation to peripheral blood mononuclear cells may be the cause of this alteration, which could be part of a more diffuse opioid system derangement in migraine subjects. PMID- 1298217 TI - Prevention of Lyme disease after tick bites. A cost-effectiveness analysis. AB - BACKGROUND: In areas of endemic disease, the probability of Lyme disease after a tick bite ranges from about 0.012 to 0.05. Early treatment with oral antibiotics prevents most complications of Lyme disease, but antibiotics are generally not prescribed until rash or other symptoms develop. METHODS: We used decision analysis to evaluate the outcomes, costs, and cost effectiveness of three alternative strategies to treat patients bitten by ixodes ticks in areas of endemic Lyme disease: empirically treat all patients with two weeks of doxycycline, treat only patients in whom erythema migrans develops, and treat only patients with erythema migrans or a positive serologic test for Lyme disease one month after exposure. RESULTS: Empirical treatment is the least expensive strategy and results in the fewest cases of Lyme disease and the fewest complications when the probability of Borrelia burgdorferi infection after a tick bite is 0.036 or higher. For probabilities of infection below 0.036, empirical therapy prevents most major complications, sequelae, and adverse events, but it incurs additional minor complications, especially as the probability of infection falls below 0.01. CONCLUSIONS: Empirical treatment of patients with tick bites is indicated when the probability of B. burgdorferi infection after a bite is 0.036 or higher, and this treatment may be preferred when the probability of infection ranges from 0.01 to 0.035. When the probability of infection after a tick bite is less than 0.01, empirical therapy is not warranted. PMID- 1298218 TI - Syphilis in the 'unbooked' pregnant woman. AB - To determine the prevalence of syphilis in the 'unbooked' pregnant woman attending King Edward VIII Hospital, Durban, mothers who had no previous history or record of antenatal care were studied over a 3-month period. One hundred and fourteen mothers were recruited, 35 (30.7%) of whom had reactive syphilis serology. None had clinical evidence of primary or secondary syphilis. Clinical evidence of congenital syphilis was found in 4 of the 35 (11.5%) babies born to mothers with reactive syphilis serology. While the fluorescent treponemal antibody absorption (FTA-ABS) IgG test was positive in umbilical cord and neonatal venous blood of all 35 babies, the FTA-ABS IgM test was negative in all specimens, including the sera from the 4 babies with clinical signs of syphilis. The FTA-ABS IgM test is therefore of little value for the laboratory confirmation of congenital syphilis. It also has limitations when it comes to screening asymptomatic neonates born to mothers with reactive syphilis serology. PMID- 1298219 TI - Seasonal variation in the incidence of ruptured abdominal aortic aneurysm. AB - This retrospective study was performed in order to correlate the season with the risk of rupture of an abdominal aortic aneurysm (AAA). From December 1968 to December 1990, 224 patients, 203 males (90.63%) and 21 females (9.37%), mean age 71 years, underwent surgery either urgently because of rupture or expansion (group A, 66 patients, 22.46%) or electively (group B, 158 patients, 70.53%) for AAA. Of the 66 patients in group A, 61 were male (92.4%) and five female (7.55%) with a mean age of 73 years. Of the 158 patients in group B, 142 were male (89.8%) and 16 female (10.1%). The frequency distribution of electively admitted and operated cases of AAA was shown to be similar during all seasons but the admissions of ruptured AAA were shown by non-parametric statistical analysis to increase during the autumn (p less than 0.05) with 43.9% of the cases being admitted during September, October and November. The male to female ratio and the ratio of the number of aneurysms ruptured to the total number of aneurysms did not change significantly. The explanation of this phenomenon is obscure and needs further epidemiological investigation to assess the seasonal variability or various parameters such as hypertension. PMID- 1298220 TI - Patients' rights vs animal rights. PMID- 1298221 TI - A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. AB - BACKGROUND: Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin. METHODS: We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred. RESULTS: For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001). CONCLUSIONS: Valproate is as effective as carbamazepine for the treatment of generalized tonic clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects. PMID- 1298222 TI - Sex differences in the brain. PMID- 1298223 TI - Current management of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is usually a relentlessly progressive disease leading to joint damage and disability. While the long-term value of disease-modifying drugs is still questioned, the quality of life of RA patients has improved, possibly reflecting the earlier more aggressive and multifaceted approach to management and/or the innate attenuation in the disease over recent years. PMID- 1298224 TI - Oral cephalosporins. PMID- 1298225 TI - Interpreting hoofbeats: can Bayes help clear the haze? PMID- 1298227 TI - Changing concepts in chronic sinusitis. PMID- 1298226 TI - Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. AB - BACKGROUND: Fertility is reduced in female rats exposed to levels of nitrous oxide similar to those found in some dental offices. Epidemiologic studies have suggested an association between exposure to mixed anesthetic gases and impaired fertility. We investigated the effects of occupational exposure to nitrous oxide on the fertility of female dental assistants. METHODS: Screening questionnaires were mailed to 7000 female dental assistants, ages 18 to 39, registered by the California Department of Consumer Affairs. Sixty-nine percent responded. Four hundred fifty-nine women were determined to be eligible, having become pregnant during the previous four years for reasons unrelated to the failure of birth control, and 91 percent of these women completed telephone interviews. Detailed information was collected on exposure to nitrous oxide and fertility (measured by the number of menstrual cycles without contraception that the women required to become pregnant). RESULTS: After controlling for covariates, we found that women exposed to high levels of nitrous oxide were significantly less fertile than women who were unexposed or exposed to lower levels of nitrous oxide. The effect was evident only in the 19 women with five or more hours of exposure per week. These women were only 41 percent (95 percent confidence interval, 23 to 74 percent; P less than 0.003) as likely as unexposed women to conceive during each menstrual cycle. CONCLUSIONS: Occupational exposure to high levels of nitrous oxide may adversely affect women's ability to become pregnant. PMID- 1298228 TI - Protection against ultraviolet radiation. PMID- 1298229 TI - Risk of and prophylaxis for venous thromboembolism in hospital patients. Thromboembolic Risk Factors (THRIFT) Consensus Group. PMID- 1298230 TI - Health checks for people over 75. PMID- 1298232 TI - Fatal lung abscess due to Lactobacillus casei ss rhamnosus. AB - A fatal case of community acquired pneumonia due to Lactobacillus casei ss rhamnosus is reported. Clinicians should be aware of this type of pneumonia. PMID- 1298231 TI - Use of symptoms and signs to diagnose maxillary sinusitis in general practice: comparison with ultrasonography. AB - OBJECTIVE: To establish the incidence of maxillary sinusitis in general practice and the predictive value of symptoms and signs. DESIGN: Population based study. SETTING: 9 general practices with 15,220 patients aged 15 years and older on the list. PATIENTS: 400 patients with 441 episodes in whom practitioners intended to confirm or to exclude sinusitis. MAIN OUTCOME MEASURES: Results of ultrasonography and signs and symptoms associated with positive results. RESULTS: 212 of the 441 episodes were confirmed by ultrasonography. 15.7 episodes occurred per 1000 adults per year. The five symptoms beginning with common cold (beta coefficient = 1.035), purulent rhinorrhoea (0.996), pain at bending (0.950), unilateral maxillary pain (0.640), and pain in teeth (0.606) were associated with positive results on ultrasonography. General practitioners' clinical diagnoses were correct in 177 episodes, false positive in 88, false negative in 22, and uncertain in 154. With an algorithm using the five weighted symptoms 243 of the diagnoses would have been correct, but 110 would remain uncertain and 44 cases would have been missed. CONCLUSION: The five symptoms algorithm would improve diagnostic accuracy of general practitioners, but incorrect and uncertain diagnoses cannot be avoided. PMID- 1298233 TI - Trends in the relative frequency of histologically diagnosed epithelial dysplasia and intra-oral carcinoma in Northern Ireland, 1975-1989. AB - Trends in the incidence of histologically diagnosed dysplastic lesions of the intra-oral mucosa have been investigated for the period 1975-89 in a well defined population of 1.5 million. These have been contrasted and compared with trends in the incidence of intra-oral carcinoma. Cases were ascertained from the records of all the histopathology laboratories that serve the Northern Ireland population. Over the 15-year period, there were 135 cases of histologically diagnosed epithelial dysplasia. In contrast to the significant increase in the incidence of intra-oral carcinoma, there was no significant change in the annual age standardised incidence of dysplastic lesions over the period. The ratio of malignant to dysplastic diagnoses rose from 2.5:1 to 5.4:1. Only 24 of the dysplastic lesions were known to have subsequently progressed to malignant carcinoma, representing 4.5% of all invasive tumours diagnosed during 1975-89. The results highlight a number of unresolved issues regarding the natural history of intra-oral carcinoma. PMID- 1298234 TI - Confounding in epidemiological studies: why "independent" effects may not be all they seem. PMID- 1298235 TI - Role of dopamine in mood disorders. PMID- 1298236 TI - External carotid air bubbles detected by transcranial Doppler. PMID- 1298237 TI - Antiembolic filters: the state of the art. PMID- 1298238 TI - Spare mass spectrometer vs linking systems in the event of a single system failure. PMID- 1298239 TI - Phacoemulsification by residents. PMID- 1298240 TI - Fistulotomy and marsupialisation for simple fistula-in-ano. PMID- 1298241 TI - Anaphylactoid reaction to ethanol. PMID- 1298242 TI - Nurse practitioners and family medicine. PMID- 1298243 TI - Health reforms. PMID- 1298244 TI - Disulfiram linked with probation. PMID- 1298245 TI - Risk of HIV infection from blood transfusion. PMID- 1298246 TI - IV fentanyl PCA during labour. PMID- 1298248 TI - How do nurses 'care'? PMID- 1298247 TI - Contrast media comparisons. PMID- 1298249 TI - Propofol and awareness. PMID- 1298250 TI - General practice and drug misuse. PMID- 1298251 TI - Which antibiotic for epiglottitis? PMID- 1298252 TI - Thallium scans in syndrome X. PMID- 1298253 TI - Bacterial overgrowth and gastric dysfunction. PMID- 1298254 TI - Vocal cord movement on induction of anaesthesia. PMID- 1298255 TI - Outcome of breech delivery at term. PMID- 1298256 TI - Salivary testing for HIV infection. PMID- 1298257 TI - Transfusing Yersinia enterocolitica. PMID- 1298258 TI - Abortion in the first trimester. PMID- 1298259 TI - Euthanasia. PMID- 1298260 TI - Social class differences in infant mortality. PMID- 1298261 TI - Suicide in the elderly. PMID- 1298262 TI - A case of fibromuscular dysplasia and aortic dissection. PMID- 1298263 TI - Misclassification bias related to the definition of a covariate. PMID- 1298264 TI - Streptococcal gangrene and purpura fulminans. PMID- 1298265 TI - Continuous flow modification for Siemens Servo 900C ventilator. PMID- 1298266 TI - Analysis of the organophosphate-induced electromyographic response to repetitive nerve stimulation: two types of end-plate depolarization account for the two most common patterns of decrement. PMID- 1298267 TI - Radionuclides in the investigation of peripheral vascular disease. PMID- 1298268 TI - Unto the least of these. PMID- 1298269 TI - Chronic fatigue syndrome: a joint paediatric-psychiatric approach. PMID- 1298270 TI - Fibromyalgia: comment on the article by Russell et al. PMID- 1298271 TI - Renal and immunological effects of occupational exposure to inorganic mercury. PMID- 1298272 TI - Cone biopsy. PMID- 1298273 TI - Pasteurella haemolytica diagnosis questioned. PMID- 1298274 TI - Omeprazole does not interact with DNA. PMID- 1298275 TI - The resonator theory of colour vision. PMID- 1298276 TI - Quinine for children with severe and complicated malaria. PMID- 1298277 TI - Cannibalism in laying hens. PMID- 1298278 TI - An analysis of the concept of homesickness. PMID- 1298279 TI - Chemotactic factors, passive invasion and metastasis of cancer cells. PMID- 1298280 TI - Pancreas transplantation: do patients benefit? PMID- 1298281 TI - Nonsurgical therapy of a splenic rupture in a hemophiliac. PMID- 1298282 TI - Comment: selective decontamination of the digestive tract. PMID- 1298283 TI - Nursing more than bathing patients, making beds. PMID- 1298284 TI - Ethics--food for thought. PMID- 1298285 TI - A celebration of public health nursing. PMID- 1298286 TI - Clinic management: from chaos to control. PMID- 1298287 TI - Modern management practices applied in a county health department. PMID- 1298288 TI - Pediatric case management: a holistic approach. PMID- 1298290 TI - A proud tradition: the Virginia C. Phillips community health day. PMID- 1298289 TI - A dream come true: one-stop shopping. PMID- 1298292 TI - Musings of a public health nurse. PMID- 1298291 TI - Public health nurses, points of light. PMID- 1298293 TI - Construction and implementation of QRST-wave simulation model. AB - Computer simulation study of the electrical activity of the heart is one of the frontier subjects of electrocardiogram (ECG) theory study. A new algorithm for simulating excitation propagation within the heart is presented in this paper. On the basis of this, computer simulation of QRST-wave is completed on an IBM PC microcomputer. All performance of the model is compared favourably with that of the models implemented on main frames or on high-performance work stations abroad. PMID- 1298294 TI - Study on the nanosecond transient absorption spectra of hypocrellin A. AB - In this paper, the nanosecond transient absorption spectra and the fluorescence spectra of Hypocrellin A(HA) are examined in solvents of varying polarity. There are three absorption bands in dilute HA solutions: Ia, IIa are defined as the triplet-triplet absorption of HA, the band IIIa is supposed to be the absorption of the solvent-separated ion pair (SSIP). In more concentrated solutions, only the absorption of SSIP was observed. The effects of solvent polarity on transient absorption spectra and fluorescence spectra of HA and the effect of oxygen on the intensities of the fluorescence of HA are discussed. Then a reasonable mechanism for the photolysis of HA is proposed. PMID- 1298295 TI - Coronary vascular remodeling and coronary resistance during chronic ischemia. AB - Our previous observations that minimal coronary resistance (MCR) decreases by 60% in a model of chronic ischemia suggest that angiogenesis and vascular remodeling occurred. To test this hypothesis we conducted quantitative morphometry on the arteriolar (ART) and capillary (CAP) beds of 14 pigs subjected to chronic ischemia. We induced chronic ischemia by ameroid occlusion of the left circumflex coronary artery for 2 to 8 weeks. We measured numerical densities (ND) and total cross sectional areas (CSA) of the ART and CAP in the ischemic regions. In the same pigs minimal coronary resistance (MCR) was measured during adenosine infusion, using a constant pressure coronary perfusion pump. In 8 other pigs we gave tritiated thymidine to determine the extent of DNA synthesis in smooth muscle and endothelial cells. At autopsy we injected colored silicone into the vessels of these pigs so we could evaluate the coronary collateral vessels as well as the other arterioles. After 3 weeks of ameroid occlusion, ART ND increased 45% above control, while ART CSA increased 21% above control. After 8 weeks of ameroid occlusion, there were further significant increases in ART CSA, but not in their ND. These changes corresponded to a decrease in MCR to 35% of control after 3 weeks of ameroid occlusion. After 8 weeks of ameroid occlusion, MCR had increased to 49% of control, however there was a further increase in ART CSA to 58% above control. DNA synthesis was occurring since endothelial and smooth muscle cells had total DNA labeling indexes of 1.2% (compared to 0.01% for controls) 2-5 days after ameroid occlusion, but were near control levels by 8 weeks. Many arterioles showed endothelial cell denuding and medial damage. Also capillaries showed degenerative changes and new sprouts. Silicone casts of the left circumflex bed vessels showed increased volumes averaging 55% more than controls. These data imply that angiogenesis is partly responsible for the decreased minimal coronary resistance seen in chronic ischemia. The loss of wall integrity in old arterioles and increased compliance in newly formed arterioles and capillaries also may contribute to the reduced resistance. Newly formed vessels are a significant portion of the total number of vessels. The combined effect of these changes is a reduced minimal coronary resistance that is modulated by 8 weeks. Measurements of coronary collateral growth paralleled the changes in the ischemic bed suggesting that angiogenesis factors controlling growth in both the bed at risk and its periphery are controlled by similar temporal events. PMID- 1298296 TI - Effects of isoproterenol (I) on the release of atrial natriuretic peptide (ANP) from isolated atria. PMID- 1298297 TI - Antioxidants and the cardiomyopathy of Mg-deficiency. AB - For several decades the animal models of Mg-deficiency have been studied with particular attention to the cardiomyopathy that develops due to dietary deficiency. In recent years we have studied the effects of nutrients and drugs with antioxidant properties on the development of the cardiomyopathy. We have found that treatment of the Mg-deficient animals with alpha-tocopherol, a naturally-occurring antioxidant, significantly diminishes the number and size of lesions. In addition, treatment with lipophilic drugs with antioxidant properties (probucol, propranolol) or water-soluble drugs that scavenge hydroxyl radicals (captopril, epicaptopril), also provided significant protection. In view of these findings, we suggest that chronic hypomagnesemia results in a pro-inflammatory condition leading to excessive production of oxygen-derived free radicals. Subsequently, the tissue antioxidant capacity is overwhelmed and oxidative tissue destruction results. PMID- 1298298 TI - Effect of propionyl-L-carnitine on experimental induced cardiomyopathy in rats. AB - The purpose of this study is to evaluate the ability of propionyl-L-carnitine, a carnitine derivative to prevent cardiac dysfunction induced by erucic acid and streptozotocin treatment in rats. Rats were fed for 10 days with normal or 10% erucic-acid-enriched diet with or without propionyl-L-carnitine injected intraperitoneally (1 mM/kg daily). Another group of rats was injected for 8-10 weeks with streptozotocin (65 mg/kg) with or without propionyl-L-carnitine intraperitoneally injected at the same dosage. Thereafter the animals were sacrificed and the hearts isolated and perfused aerobically. When isovolumic measurements of left ventricular function were applied, there was no difference in mechanical activity between treated and control hearts. On the contrary, when pressure-volume curves were determined in the paced hearts, the pressure developed by hearts from erucic acid-treated or diabetic rats was reduced. Propionyl-L-carnitine always produced positive inotropy. This was true for the control-saline treated rats that received the drug, as well as for the hearts isolated from cardiomyopathic animals. These data suggest that propionyl-L carnitine, when given chronically, is able to overcome myocardial dysfunction caused either from erucic acid treatment or diabetes. PMID- 1298299 TI - The creatine kinase system and cardiomyopathy. AB - Changes in the creatine kinase system, cellular energetics, regulation of respiration and alterations in parameters of contractility in experimental animals (myopathic hamsters), and in patients with dilated cardiomyopathy were studied. 31P-NMR methods were used to show that cardiomyopathic hearts are characterized by decreased work index, lower tissue ATP, phosphocreatine, and total creatine contents and diminished creatine kinase activity and energy fluxes. In isolated mitochondria, only the creatine kinase activity was decreased. Both in cardiomyopathic hamsters and human hearts a share of mitochondrial creatine kinase in the total tissue enzyme activity was decreased from 33% to 18% and that of BB elevated from 5% in control to 20%, at an unchanged relative level of MM. In saponins-skinned cardiac fibers on cardiomyocytes creatine (Cr, 25 mM) decreased Km for ADP in regulation of respiration from 133 +/- 20 to 20 +/- 4 microM due to activation of coupled mitochondrial creatine kinase-oxidative phosphorylation reactions in control hamster hearts. In the case of cardiomyopathy it decreased Km for ADP only to 81 +/- 13 microM. In endocardial biopsy samples from the hearts of patients with dilated cardiomyopathy taken during angiography, creatine stimulated respiration was decreased by 36% of control value, which correlated well with increase of end diastolic pressure and fall in ejection fraction. Thus, changes in mitochondrial creatine kinase expression diminished the efficiency of cellular regulation of respiration in cardiomyopathic hearts that may have functional consequences for hemodynamics or may be adaptive alterations in response to decreased contractility. PMID- 1298300 TI - Exposure to free radicals alters ionic calcium transients in isolated adult rat cardiac myocytes. AB - Oxygen-derived free radical production has been documented to occur on reperfusion of the ischemic myocardium. Intracellular ionic calcium ([Ca++]i) levels in isolated adult rat cardiac myocytes exposed to free radicals were evaluated using fura-2. The effect of different time periods of free radical exposure on altering [Ca++]i was examined. Myocytes were either exposed to the free radical generating system continuously or exposed for 5 or 10 minutes and then returned to the HEPES buffer. Myocytes maintained in HEPES buffer or the HEPES buffer containing purine and iron-loaded transferrin continued to stimulate, exhibited relatively uniform 340/380 nm ratios and maintained a rod shape. Continuous exposure to free radicals resulted in a significant increase in [Ca++]i. Myocytes became unresponsive to stimulation at 31 +/- 7 (SE) minutes and eventually exhibited contracture. Exposure to the free radical generating system for 10 minutes resulted in a response similar to continuous exposure. Myocytes exposed to the generating system for 5 minutes exhibited regular calcium transients for 55 +/- 5 minutes. Thus, even a brief period of free radical exposure alters calcium flux and may induce subsequent myocardial damage. PMID- 1298301 TI - Contrasting effects of anoxia and graded hypoxia on single cardiac myocyte function. AB - The hypoxic cardiac myocyte has been used as a simplified model of myocardial ischemia. Precise control of oxygen tension is possible in a system with limited diffusion barriers offering an advantage over tissue preparations. This system was employed to study the effects of graded reductions in oxygen tension on cell morphology, spontaneous and electrically stimulated mechanical activity, and [Ca2+]i in single adult rat cardiac myocytes. All of 10 resting myocytes exposed to glucose-free anoxia (pO2 < .02 torr) abruptly underwent rigor contracture, retaining a clear sarcomere pattern, following a lag period of 22.6 +/- 2.8 minutes. These cells relengthened at reoxygenation 5 minutes following rigor onset. In contrast, 5 of 12 cells exposed to graded hypoxia (1-3 torr) were partially rounded and displayed a disorganized sarcomere pattern during hypoxic exposure and further shortened at reoxygenation (p = .03). Spontaneous mechanical oscillations thought to result from spontaneous sarcoplasmic reticulum calcium cycling only developed in those cells exposed to hypoxia, and their frequency was markedly enhanced in 6 of the 12 exposed cells. None of the 10 cells exposed to anoxia showed an increase in spontaneous activity. When spontaneous mechanical activity and underlying Ca2+i oscillations were induced by raising buffer [Ca2+] in 3 indo-1 loaded myocytes, anoxia abolished these as well. Cells stimulated at 0.2 Hz demonstrated spontaneous calcium oscillations and a significant rise in [Ca2+]i (indo-1 fluorescence ratio) prior to rigor onset only when exposed to graded hypoxia. Thus moderate hypoxia may cause earlier calcium loading and more progressive cell destruction than occurs during anoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298302 TI - Binding of the Kunitz-type trypsin inhibitor DE-3 from Erythrina caffra seeds to serine proteinases: a comparative study. AB - The effect of pH and temperature on kinetic and thermodynamic parameters (i.e., k(on),k(off),Ka,delta G0, delta H0 and delta S0 values) for the binding of the Kunitz-type trypsin inhibitor DE-3 from Erythrina caffra seeds (ETI) to bovine beta-trypsin, bovine alpha-chymotrypsin, the human tissue plasminogen activator, human alpha-, beta- and gamma-thrombin, as well as the M(r) 33,000 and M(r) 54,000 species of the human urinary plasminogen activator (also named urokinase) has been investigated. At pH 8.0 and 21.0 degrees C: (i) values of the second order rate constant (K(on)) for the proteinase:ETI complex formation vary between 8.7 x 10(5) and 1.4 x 10(7)/M/s; (ii) values of the dissociation rate constant (k(off)) for the proteinase: ETI complex destabilization range from 3.7 x 10(-5) to 1.4 x 10(-1)/s; and (iii) values of the association equilibrium constant (Ka) for the proteinase:ETI complexation change from < 1.0 x 10(4) to 3.8 x 10(11)/M. Thus, differences in k(off) values account mostly for the large changes in Ka values for ETI binding. The affinity of ETI for the serine proteinases considered can be arranged as follows: bovine beta-trypsin > human tissue plasminogen activator > bovine alpha-chymotrypsin >> human alpha-, beta- and gamma-thrombin approximately M(r) 33,000 and M(r) 54,000 species of the human urinary plasminogen activator. Moreover, the serine proteinase:ETI complex formation is an endothermic, entropy-driven, process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298303 TI - Molecular recognition and self-replication. AB - Self-replicating molecules stand at the very boundary of chemistry with biology. This review describes the development of synthetic structures capable of self replication from studies in molecular recognition. The weak intermolecular forces -hydrogen bonds and aromatic stacking interactions--that characterize interactions of nucleic acid components were designed into synthetic receptors for adenine. Covalent conjugates of these receptors with adenines gave self complementary structures capable of replication. The new systems feature autocatalysis, sigmoidal product growth and even mutation. General rules for the design of replicating systems are described and these suggest that the evolution of replicating molecules was an inevitable event. PMID- 1298304 TI - Intermolecular interactions in type I collagens. AB - X-PLOR modelling of collagen dimers containing Gly-Glu-Arg in each chain has been carried out. The interaction between molecules when two Gly-Glu-Arg are present on each chain is found to be substantially less than two times that obtained with one per chain, implying that relative tilting of two collagen molecules does not offset the disadvantages of misalignment of the interacting moieties. This implies that if multiple (Glu(-)-Arg+)3 interactions are important in fibril formation, their lateral separations must be large enough to insure that they act independently. PMID- 1298305 TI - Strand orientation of [alpha]-oligodeoxynucleotides in triple helix structures: dependence on nucleotide sequence. AB - The aims of the present theoretical study of the conformations of [alpha] oligodeoxynucleotides forming triple helices with DNA duplexes are to understand the structural and energetic factors involved in [alpha]-triple helix formation by means of energy minimization, and to explain the experimentally observed dependence of strand orientation on the nucleotide sequence. It is found that the energetically preferred orientation of the [alpha]-oligonucleotide with respect to the homopurine strand depends on the sequence of the homopurine.homopyrimidine tracts. This is a consequence of the structural heteromorphism of base triplets in the intrinsically more stable reverse Hoogsteen hydrogen bonding configuration. Practical rules are proposed for determining the orientation of the nuclease-resistant [alpha]-oligodeoxynucleotide strand which will form the most stable triple helix. PMID- 1298306 TI - [Quantitative analysis of oculomotor functions in various age groups of normal subjects]. AB - The oculomotor functions were studied in 50 normal subjects aged 20 to 60 years. The experiments consisted of saccadic test, smooth pursuit eye movement and optokinetic nystagmus. The normal values and sensitive indicators of ageing were obtained. With increase in age, the latency of saccade was prolonged (P < 0.05) and its accuracy showed a tendency to decrease. There was no relationship between the velocity gain of eye movement and age during two amplitudes and velocities of smooth pursuit test, but its total harmonic distortion was increasing with ageing. With increase in optokinetic velocities from 10 degrees/s to 40 degrees/s the velocity gain of eye movement decreased in all groups, but its values in > 40 year-groups decreased more than < 40 year groups. During high velocity optokinetic stimulation, the gain was more obviously decreased in elder age group. PMID- 1298307 TI - [Vestibular velocity step test and normal limits for the Chinese]. AB - Vestibular velocity steps test (VVST) to impulsive stimulus of horizontal rotation (90 degrees/S and 180 degrees/S) were performed in 22 normal subjects. Gain (G) was defined as the ratio of the initial slow phase eye velocity (ISPV) to head velocity. The time constant (T) was the time to find the point where it was 0.37 of ISPV. Duration (D) of induced nystagmus was the time between first and final nystagmus. The directional preponderance (DP) for G, T and D was calculated from the formula, (R-L)/(R+L) x 100%. These normal limits were 0.37 1.09 and 0.27-0.83 for G, 8.0--20.4s and 6.5-17.3s for T, 30.4-65.0s and 30.0 54.4s for D, +/- 21.4% and +/- 21.5% for DP(G), +/- 24.2% and +/- 20.3% for DP(T), +/- 16.5% and +/- 17.9% for DP(D) of 90 degrees/S and 180 degrees/S, respectively. The advantages and shortcomings of VVST and its value were discussed. PMID- 1298308 TI - [Value of bush spike wave in diagnosis of central lesions]. AB - Bush spike wave was a kind of wave during ENG-Gaze test. We analysed 440 cases. The results showed that appearance rate of organic lesions of the brain was 55%, peripheral and other lesions were few. So bush spike wave might be of certain value in differential diagnosis of central lesions. PMID- 1298309 TI - [Effects of biomicrosphere on the cochlear blood flow, blood pressure and heart rate in guinea pigs]. AB - Cochlear blood flow (CBF) in guinea pigs was measured by Laser Doppler flowmeter and biomicrosphere method. The effects of dosages of biomicrospheres and time factor on the CBF, blood pressure and heart rate were observed. The findings suggest that 9 x 10(6). 10.5 x 10(6) biomicrospheres may be most suitable for measuring CBF with biomicrosphere method, and some physiological parameters of the guinea pig must be taken down within 2-10 minutes after microsphere injection. PMID- 1298310 TI - [Degeneration and regeneration of olfactory epithelial neurons after olfactory nerve sectioning]. AB - The morphological changes of olfactory mucous membrane have been investigated with light microscope and T.E.M. within a period of 3 days to 4 weeks after unilateral olfactory nerve sectioning. No obvious morphological changes of supporting cells and Bowman's gland cells were seen in any group postoperatively. A degeneration in some neurons began to appear on the third day following the operation and reached its peak about one week after operation. No changes of the basal cells were seen on the third day. After one week, however, they changed into globose type and some of which showed mitotic activity. Within 2-4 weeks, the globose cells differentiated gradually into mature neurons. Four weeks after the operation, the regenerated olfactory epithelium appeared similar to that of the control group. The main feature of neuron degeneration was the increase in plasma electron density. In serious cases, the organelle systems disappeared and the nuclei were pyknotic. The results obtained from this experiment shows that after the sectioning of olfactory nerve, degeneration and regeneration processes of olfactory neuron will occur; and the regenerated neuron may possibly be developed from basal cells. PMID- 1298311 TI - [Repair of cerebrospinal rhinorrhea]. AB - The present paper describes a new method for repairing the CSF rhinorrhea from the sella turcica using frontal muscle--galea aponeurotica--periosteum flap with blood vessel pedicle through cranial-nasal approach. This new method possesses the following advantages: short approach, clear field of vision, nose injury, few complications and less cosmetic influence. The flap, led into the sphenoid sinus Via the frontal sinus or the anterior cranial base and nasal roof, Survived and grew well due to its sufficient circulation and strong resistance to infection. For all the five cases described in this paper, among which three had accepted two or three repairs before, the CSF rhinorrhea ceased after only one procedure. PMID- 1298312 TI - [Significance of X-ray computed tomography analysis in invasion and lymph node metastasis and TNM classification of nasopharyngeal carcinoma]. AB - From 1986-1990, 100 NPC patients, proved by pathology and CT scan before treatment, were selected for analysis to observe the relationship between CT features and clinical signs of NPC. The common routes of invasion and metastasis of NPC were analysed. Furthermore, advantages of CT on TNM classification of NPC were discussed. PMID- 1298313 TI - [Serum beta 2-microglobulin determination in nasopharyngeal carcinoma patients. An analysis of 139 cases]. AB - Serum beta 2-microglobulin (beta 2-M) was determined in normal adults, patients with chronic nasopharyngeal inflammation and nasopharyngeal carcinoma (NPC) by the radioimmunoassay (RIA). The mean value in normal adults was 2023.85 +/- 454.32 micrograms/L, that in patients with chronic nasopharyngeal inflammation was 3294.65 +/- 1320.89 micrograms/L. The mean value in patients with NPC was significantly higher than those in patients with chronic nasopharyngeal inflammation and normal adults (P < 0.01). But there was not significant difference between mean values of patients with chronic nasopharyngeal inflammation and normal adults (P > 0.05). It is suggested that the RIA of beta 2 M is a useful assay in the diagnosis of NPC. PMID- 1298314 TI - [Research on the origin of middle and long-latency auditory evoked potentials]. PMID- 1298315 TI - Biologic esthetic restorations. AB - Cases of serious coronal destruction were treated by bonding parts of extracted teeth to the coronal remnants by means of adhesives and photo-activated composite resins. The long-term clinical results have revealed very satisfactory clinical performance of the compounded restorations. No detrimental effects have been identified. PMID- 1298316 TI - Effect of cavity disinfection on bond strength to dentin. AB - The application of a disinfecting step in cavity preparation and tooth restoration is gaining wider acceptance. This study examined the effect of two commercially available disinfecting agents on the shear bond strength to dentin using a fourth generation dentin bonding agent. The agent tested permitted an evaluation of both dry and wet bonding techniques. It was found that the commercial preparations did not adversely affect shear bond strength to dentin in either the dry or wet application. PMID- 1298318 TI - New technique for the use of a precision attachment in the fabrication of a cast crown/core and post unit: procedures and case report. PMID- 1298319 TI - Clinical evaluation of castable ceramic veneers. AB - Laboratory fabricated veneering of discolored or malformed anterior teeth is becoming a widely used technique. Etched Dicor and Dicor Plus ceramic veneers cemented with Dicor Light Activated Cement with Fluoride is one technique available to the practitioner. The purpose of this study was to evaluate the clinical effectiveness of castable ceramic veneers and the cementation system. Forty-three Dicor and 18 Dicor Plus veneers were placed in 12 patients. An intraenamel preparation was completed with a bullet-nosed diamond bur in an ultra speed handpiece with air-water spray, and a polyvinylsiloxane impression was made. All veneers were fabricated on dies by the same laboratory technician and placed by one practitioner. The restorations were examined by two evaluators at baseline, 3 months, and 1 year, using modified Ryge criteria. PMID- 1298317 TI - Bonding composite to glass ionomer with adhesive resin cements. AB - This study was to determine the bond strength of composite to glass ionomer using the following adhesive resin cements: Imperva Dual, CB Metabond, All-Bond, Geristore, and Panavia. All materials were mixed following the manufacturer's specifications. Bonded samples were thermocycled for 2000 x between 5 degrees C and 55 degrees C. Shear bond strengths were determined using an Instron Testing Machine. No statistical differences were noted between materials at the p < .05 level of significance. In addition, scanning electron micrographs were taken of the primed glass ionomer surfaces. These micrographs revealed varying amounts of matrix dissolution along with roughened surface topographies. PMID- 1298320 TI - Bonding Ni-Cr alloy to tooth structure with adhesive resin cements. AB - This study was to determine the shear bond strengths of Ni-Cr alloy to Ni-Cr alloy (Group I), Ni-Cr alloy to enamel (Group II), and Ni-Cr alloy to dentin (Group III) using Imperva Dual, DC Metabond, All-Bond, Geristore, and Panavia. All bonded specimens were thermocycled 2000 x (5 degrees C-55 degrees C) after 24 hours and subjected to shear bond testing on a Universal Instron Testing Machine. In all groups of the study, Imperva Dual and CB Metabond had significantly (p < .05) higher bond values than Panavia. PMID- 1298321 TI - Quantitative analysis of six composite polishing techniques on a hybrid composite material. AB - Determining the best technique for finishing and polishing composite resins is important to ensure longevity of the restoration and prevention of recurrent decay and periodontal disease. This study quantitatively compared the surface roughness of a small particle hybrid composite material finished and polished using six different techniques. Five composite samples were randomly assigned to one of six polishing techniques. Uniform composite surfaces were prepared by finishing samples with a 600-grit carborundum disk prior to polishing. The unpolished surfaces were analyzed with the Taylor-Hobson Talysurf 10 surface texture measuring instrument. The surfaces were then polished and analyzed again. There were no statistical differences among treatment groups prior to polishing. There was a statistical difference between treatment groups after polishing. The smoothest surfaces were obtained using Centrix System rubber points alone, Centrix System rubber points plus Caulk's Prisma Gloss fine and super-fine pastes, and Caulk's Enhance disks plus Caulk's Prisma Gloss fine and super-fine pastes. There was no statistical difference between these methods and 3M Sof-flex disks alone. The roughest surface was produced by the Enhance disks only without using the Prisma Gloss pastes. There was no statistical difference between this method, however, and the use of Sof-flex disks plus Kerr's Lustre Paste. Lustre Paste, included with Herculite kits, did not improve a surface polished with Sof flex disks. PMID- 1298322 TI - Marginal leakage of a new adhesive restorative system: a preliminary in vivo investigation. AB - The efficacy of newly developed adhesive restorative materials is commonly described by in vitro test results such as bond strength and microleakage data. Due to the inconsistency often found between in vitro testing and in vivo performance, the purpose of the present investigation was to restore teeth scheduled for extraction in vivo with an experimental restorative bonding system and to evaluate the microleakage of the restorations by common laboratory techniques following extraction after 3 months of clinical service. Two restorations were placed in each of seven anterior teeth, one in the middle of the labial enamel portion and the other labially extending over the cementoenamel junction (CEJ). Six of the seven fillings completely surrounded by enamel showed no microleakage. However, two of the restorations crossing the CEJ revealed microleakage originating from the cervical margins. In spite of the small number of fillings assessed, the experimental enamel-dentin adhesive compound tested is preliminarily considered a promising new system. PMID- 1298323 TI - Esthetic arch bar for maxillomandibular fixation in orthognathic surgery. AB - Arch bars are well-known dental appliances for the management of fractures and orthognathic surgery. Traditionally both the commercially available, prefabricated arch bars as well as the custom-made arch bars are made of metal so as to provide good rigidity. Each of these types of arch bars has its own advantages as well as drawbacks. This article looks at a type of custom-made arch bar that is easy to construct and use. At the same time, it provides good rigidity, fit, and esthetics. PMID- 1298324 TI - Effect on dentinal adhesives on marginal adaptation and cavity sealing with resin restorations in vitro. AB - In a companion article in this issue and a previous article in this journal, two experimental enamel dentin adhesive systems were evaluated and compared with four commercially available resin bonding agents by SEM investigation of the tooth adhesive interfaces and by determination of bond strengths to enamel and dentin under various conditions. In continuation of these screening investigations, the present article describes the results of cavity tests for assessment of marginal adaptation by measurement of gap dimensions, and of cavity sealing by rating of microleakage, when standardized dentin cavities were treated with the adhesive restorative systems. Both tests resulted in the same ranking of the six materials. Gluma, Clearfil Photo Bond, and two experimental compounds showed very narrow gaps and moderate microleakage. In contrast, Prisma Universal Bond 2 (the material has been replaced in the market by Prisma Universal Bond 3) and Scotchbond 2 showed significantly wider marginal gaps and more pronounced microleakage. Final discrimination between the efficacy of adhesive restorative materials by any of the currently used in vitro tests is disputable and prediction of long-term clinical performance by laboratory test data remains questionable. PMID- 1298325 TI - Tunnel restorations: a review. AB - Conventional cavity designs are coming under increased scrutiny because of an increased emphasis on preservation of tooth substance. The tunnel restoration when used with glass ionomer, may overcome some of the disadvantages of conventional cavity preparations. Justification for the use of the tunnel restoration is from a limited number of short-term clinical observations and destructive laboratory testing of marginal ridge strength. The technique is not without shortcomings. Long-term clinical and nondestructive laboratory trials examining the strength of teeth with tunnel restorations should be undertaken prior to its acceptance as a replacement for techniques in which the marginal ridge is removed. PMID- 1298326 TI - Comparative in vitro evaluation of recent enamel and dentin adhesive materials. AB - In this in vitro study, two experimental and four commercially available enamel dentin bonding agents are characterized by shear bond strengths to human teeth following storage of the specimens for 2 minutes, 15 minutes, and 24 hours, respectively, or after stressing of the bonds by 5000 thermal cycles between 5 degrees and 55 degrees C. It is assumed that the experimental compounds are clinically adequate materials to mediate long-term retention of resin restorations placed without reliance on mechanical undercuts. The limitations of such in vitro strength data regarding clinical performance are discussed and emphasized. PMID- 1298327 TI - Compressive and diametral tensile strength of titanium-reinforced composites. AB - This article determines the compressive and diametral tensile strength of two titanium-reinforced composites (Bis-GMA-based), Ti-Core and Flexi-Flow cem with titanium and compares their strengths to dentin and commercially available core materials and cements. In addition scanning electron microscope (SEM) photographs were taken of Ti-Core and Flexi-Flow cem with titanium. Compressive and tensile loading was performed on a modified universal testing apparatus. Ti-Core and Flexi-Flow cem with titanium were measured to have compressive strengths of 41,132 and 41,876 psi and tensile strengths of 5219 and 4930 psi, respectively. Statistically (ANOVA, one-way analysis of variance), these titanium-reinforced composites are stronger in compressive and tensile strength than Ketac-Silver, Fleck's zinc cement, Durelon, Ketac-Cem, and GC Miracle Mix. Both titanium reinforced composite materials approach the compressive and diametral tensile strengths of dentin (43,100 and 6000 psi). SEMs revealed that the titanium was uniformly and homogeneously interspersed within the resin matrix of the material. PMID- 1298328 TI - Noncarious cervical lesions: the decision to ignore or restore. AB - A variety of unusual noncarious cervical lesions (NCL) are depicted that appear to negate W.D. Miller's toothbrush/dentifrice abrasion theory and demonstrate that other factors may be involved in their etiology. Confusion exists in the designation of NCL ever since G.V. Black stated in 1908 that toothbrush/dentifrice abrasion is an erosive effect. Since abrasion and erosion are two distinct activities, it is suggested that dentistry adopt the same terminology as chemical engineering in order to foster improved communication between the sciences. The term "abfraction" has been used to supplant erosion because it seems more appropriate when describing the loss of tooth substance attributable to effects of occlusal loading forces as well as the physiochemical breaking that occurs during stress corrosion. Numerous reasons, based on accepted engineering principles, indicate that NCL should be restored. It is incumbent on dentists to become cognizant of these reasons, since this would help them inform patients of the benefits to be gained by restoring such deficient areas. PMID- 1298329 TI - Esthetic posterior restorations: indirect composite resin inlays and onlays. PMID- 1298330 TI - Diastema closure: a case report. AB - This clinical study describes two combined modalities of treatment, orthodontic and porcelain laminate placement, to facilitate diastema closure. Geristore, a dual-cure fluoride-releasing composite was mixed to bond orthodontic brackets in place. H6 elastic bands were used with the orthodontic brackets to close the diastemas sufficiently and to allow the placement of Cerinate porcelain laminates to produce a beneficial cosmetic effect. PMID- 1298331 TI - Hepatitis B virus-related markers in secondary and in essential mixed cryoglobulinemias: a multicentric study of 596 cases. The Italian Group for the Study of Cryoglobulinemias (GISC). AB - The aim of this study was to assess the prevalence of HBV-related markers in cryoglobulinemias and the possible association between hepatitis B virus (HBV) and essential mixed cryoglobulinemia (EMC). A retrospective survey of the prevalence of HBV infection in cryoglobulinemic patients was carried out in 596 cases of cryoglobulinemia. On the basis of clinical and laboratory criteria the cases were grouped as secondary to connective tissue disease, to lymphoproliferative disorders, to chronic liver diseases or to chronic infectious diseases. The cases in which an associated disease was not evidenced were considered as essential mixed cryogobulinemias. Subjects in which liver dysfunction was first diagnosed simultaneously with cryoglobulinemia, were considered as a separate group. A greater prevalence of HBsAg and anti-HBc antibodies was found in cryoglobulinemias secondary to chronic liver disease (p < 0.0001) and in those associated with liver involvement at diagnosis (p < 0.05) than that found in EMCs. The prevalence of anti-HBs antibodies did not differ significantly among the groups. Proven contact with the virus, documented by at least one positive marker, was evidenced more frequently in cryoglobulinemias secondary to liver disease than in the other groups (p < 0.01). The prevalence of HBV related markers in EMCs and in hospitalized patients not suffering from diseases associated with cryoglobulin production were similar, and seems to reflect the epidemiological situation of HBV infection in Italy. In conclusion, our findings do not support an association of HBV with EMC. PMID- 1298332 TI - [The modulator effect of bradykinin with respect to tracheobronchial clearance in healthy subjects]. AB - Bradykinin (Bk), a vasoactive nonapeptide which has been proposed as mediator in the pathogenesis of bronchial asthma, is a potent secretagogue in canine airways and in human nasal mucosa in vivo. A study was carried out in order to evaluate the effect of inhaled Bk on tracheobronchial clearance (TBC), measured by a radioaerosol technique in 10 healthy volunteers. Subjects inhaled Bk (8 mg/mL) or vehicle placebo on two occasions, at least 2 weeks apart, in a double blind and randomized fashion 30 min after radioaerosol inhalation. TBC, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 hours (AUC 0-6h), was enhanced in 9 of 10 subjects following inhaled Bk when compared to placebo. The mean values for AUC 0-6h were significantly reduced from 132%.h to 92%.h (p < 0.001) with placebo and Bk respectively. We conclude that Bk has a marked effect on tracheobronchial clearance in normal human airways. PMID- 1298334 TI - Hematological changes in infectious diseases. Hematological consequences of viral infections (1). AB - A number of distinct hematological alterations take place in the presence of infectious diseases. This review seeks to provide a diagnostic guide and prognostic criteria for the clinician in the light of the concomitant hematological changes occurring in the course of acute and chronic viral, bacterial, spirochetal and protozoal infections. The authors emphasize the fact that although certain broad principles may be applied to each type of infection, these principles may have to be interpreted with considerable latitude in any individual case, on account of the variable factors of virulence and resistance. The careful examination of blood films and bone marrow smears, supplemented when appropriate by cytochemical reactions, may be useful in the differential diagnosis of various infective states and in assessing both the severity of the pathological condition and the response of the patient. PMID- 1298333 TI - [The humoral and cellular factors of glomerular damage]. AB - The present review summarizes current concepts on glomerular non-inflammatory and inflammatory immune injury. Non-inflammatory glomerular injury can be ascribed to mechanisms involving antibody alone, terminal component of complement (C5b-9) or cytokines having as primary target the glomerular epithelial cells. These mechanisms induce changes in cell cytoskeleton and in surface distribution of adhesion molecules leading to functional alterations which may account for loss of glomerular permselectivity. Inflammatory glomerular injury is mediated by neutrophils, macrophages, platelets and lymphocytes as well as by resident glomerular cells. Cell derived mediators include proteases, reactive oxygen species, cationic proteins, cytokines and growth factors that may variably affect recruitment of inflammatory cells, proliferation of resident glomerular cells and production of extracellular matrix. These alterations may determine proteinuria, impairment of renal function and eventually progression of glomerular injury to sclerosis. The inflammatory type of glomerular injury is mainly initiated by subendothelial-mesangial immune deposits and/or activation of cell mediated immunity. The role of factors such as the nature, intensity and persistence of initiating mechanisms, the types of inflammatory cells involved and the response of intrinsic glomerular cells, in expression and progression of glomerular injury are discussed. PMID- 1298335 TI - [Atrial natriuretic factor and pulmonary function]. AB - The aim of this review is to provide a critical and concise discussion of present knowledge on the role of atrial natriuretic factor (ANF) in physiological as well as pathological pulmonary conditions. The lung contributes only to a small extent to the production of circulating ANF; on the other hand, the lung represents the major degrading site of the protein. Plasmatic ANF concentration increment during lung disease may therefore be due to a reduction in ANF plasma removal enzyme rather than to increased ANF production. Lung tissue shows more ANF receptor sites than any other organ. The effect of ANF on bronchial and pulmonary artery muscle lining is particularly evident. In fact ANF administration in asthmatic patients leads to bronchodilation comparable to dilation induced by salbutamol. Furthermore, elevated levels of circulating ANF seem to influence fluid redistribution through alveolar-capillary membrane leading to protein mobilization through the alveolar space. On the contrary, in the cardiomyopathic hamster ANF induces relevant guanylate cyclase activation before the animal has developed hemodynamic changes. Guanylate-cyclase activation may protect the lung through counteracting pulmonary edema formation, as shown by fluid reduction in alveolar spaces following pneumotoxic agents administration. This effect seems independent of natriuretic and hypotensive ANF effects. PMID- 1298336 TI - Chronic diarrhea, weight loss and hypotension. PMID- 1298338 TI - The effect of carotid sinus pressure changes on mean circulatory filling pressure in the anaesthetized rabbit. AB - The effect on mean circulatory filling pressure (MCFP) of changes in pressure within the vascularly isolated carotid sinus has been studied in anaesthetized rabbits. With the sinus exposed to arterial pressure (102 +/- 6 mm Hg; mean +/- SEM) MCFP was 6.18 +/- 0.40 mm Hg. At sinus pressures of 160 and 40 mm Hg, MCFP was 5.71 +/- 0.39 and 6.43 +/- 0.33 mm Hg respectively. The mean difference of 0.72 +/- 0.06 mm Hg between MCFP at these two sinus pressures was significant (P < 0.001). MCFP varied with blood volume when this was increased or reduced by 8%, but at each blood volume level the difference between MCFP at high and low sinus pressure remained significant (P < 0.01). The gradient for venous return, MCFP minus right atrial pressure, was altered by changes in carotid sinus pressure, being 0.60 +/- 0.12 mm Hg less at a sinus pressure of 160 mm Hg than at a sinus pressure of 40 mm Hg. This difference was significant (P < 0.01). PMID- 1298337 TI - Thyroid storm with encephalopathic symptoms due to Graves' disease and inappropriate secretion of thyrotropin. AB - A 41-year-old woman is described, first hospitalized in the neurosurgical department for a transient ischemic attack with left hemiparesis followed after 6 hours by tonic-clonic seizures starting from the left hemiface and quickly generalized. Brain computed tomography (CT) scan and magnetic resonance imaging were normal. Clinically the patient presented tremor, tachycardia, generalized muscle weakness, and profuse diaphoresis. T4 and T3 were elevated. The patient was transferred from the neurosurgical to the medical department where a thyroid storm due to autoimmune Graves' disease with normal thyrotropin (TSH) values responsive to thyrotropin-releasing hormone (TRH) stimulation was diagnosed. A syndrome of inappropriate secretion of TSH was suspected in an unusual presentation as autoimmune Graves' hyperthyroidism. The TSH alpha-subunit and alpha-subunit/TSH molar ratio were normal, which supported the diagnosis of non neoplastic inappropriate secretion of TSH. However, severe autoimmune Graves' hyperthyroidism is very rare indeed because autoantibodies to thyroid antigens are generally non-detectable in such patients. Our patient was treated initially with barbiturates, then with dexamethasone, Lugol's solution, methimazole and propranolol. Treatment of this patient proved difficult, and definitive improvement was obtained only after triiodothyroacetic acid administration, but methimazole and propranolol administration could not be discontinued. Fine needle aspiration biopsies of the thyroid in 2 occasions showed follicular or follicular papillary proliferation with lymphocytic infiltration as in chronic thyroiditis. The patient is now in good clinical conditions and is followed up regularly. Autoimmune Graves' hyperthyroidism may be associated in extremely rare instances with non neoplastic inappropriate secretion of TSH. PMID- 1298339 TI - The relationship between systolic blood pressure and microvascular resistance in non-diabetic and diabetic subjects. AB - Skin blood flow and microvascular resistance were measured in the feet of hypertensive and normotensive subjects by the non-invasive transient thermal clearance method. Skin blood flow decreased and microvascular resistance increased as a function of systolic brachial blood pressure for the non-diabetic subjects who were not treated by vasoactive medication. The relationship between blood flow and systolic blood pressure for diabetic patients and for patients who were treated by enalapril was poor. The average resistance for non-diabetic patients treated by enalapril was lower than that of untreated non-diabetic subjects. For diabetic patients no significant difference in resistance between enalapril treated and untreated patients was found. The results demonstrate that for non-diabetic patients the role of microvascular resistance in hypertension is significant while it is less important in diabetic patients. PMID- 1298340 TI - Cyclic perfusion of the lung by dense gas breathing may reduce the (A-a)DO2. AB - The decrease in the alveolar-arterial O2 difference (A-a)Do2 in dense atmosphere could be the result of cyclic lung perfusion due to large swing in pleural pressure during breathing cycles /4/. Using a mathematical model of the lung to calculate (A-a)Do2, a slight decrease was demonstrated in (A-a)Do2 as perfusion changed from steady to cyclic. The present study incorporates variable vertical partitioning of perfusion in this model, as a function of instantaneous total blood flow. This demonstrated a reduction of the Po2 difference between the apex and the base of the lung, and a reduction of (A-a)Do2, when perfusion was assumed to be cyclic, of 4.1 to 5.0 torr when blood flow was continuous throughout the breath, and of 5.0 to 5.7 torr when perfusion was assumed to be pulsatile. The results agree with experimental findings: reduction of (A-a)Do2 when breathing dense gas and improved apical perfusion in pulsatile blood flow. Calculation of the spatial VA/Q inequality suggests there is no correlation with (A-a)Do2 reduction. The decrease in (A-a)Do2 is attributed to the mixing of lung capillary blood flows having different O2 saturations. PMID- 1298341 TI - Effects of changes in plasma volume on fatal rhabdomyolysis in the rat induced by glycerol injections. AB - Rhabdomyolysis can be fatal in both experimental animals and man, but very little is known of the factors causing increased mortality in rhabdomyolysis. The aims of this study were to create an animal model of fatal rhabdomyolysis in rats by a glycerol injection into the leg muscle, and to elucidate some of the factors affecting mortality as a result of rhabdomyolysis formation. In this study, two factors which can result in increased mortality in rats as a result of glycerol injection, were examined. These factors include varying doses of 50% glycerol (0.5-2 ml/100 g) and various stages of dehydration prior to glycerol injection. Dehydration was induced by 1: chronic dehydration, in which the rats underwent water deprivation for a period of 24 to 72 hours prior to injection of glycerol; 2: acute dehydration, by the induction of either diuresis, by injecting sucrose (200-600 mg/100 g) to the femoral vein, or hemorrhage (0.7-2.1 ml/100 g). The results demonstrate that the mortality rate in rats increased in all three models of dehydration as the dose of glycerol injected to the rats increased (above a dose of 0.75 ml/100 g) and as the extent of dehydration increased. Use of a blood substitute before or after glycerol injection in order to compensate for the loss of body fluids did not increase the survival rate of the glycerol-injected rats. In contradistinction, rats treated with non-lethal doses of glycerol exhibited substantial resistance to a second lethal dose of glycerol, injected two weeks following the first injection. PMID- 1298342 TI - Evidence against oxidant injury and endotoxin underlying glycerol-induced fatal rhabdomyolysis in rats. AB - Rhabdomyolysis in experimental animals and in man may be fatal. The mechanism of action causing death in man and in the experimental model of laboratory animals injected with glycerol in a dose causing fatal rhabdomyolysis is unknown. The aim of this study was to examine two possible causes of death following glycerol injection (0.5-2 ml/100 g) to the leg muscle of rats following a period of water deprivation (24-72 h). The first factor examined was free radical formation, via the administration of various antioxidants such as natural antioxidant (NAO - 5 mg/100 g), vitamin E (0.2 mg/100 g each day for 7 days), dimethylthiourea (DMTU - 50 mg/100 g) and superoxide dismutase (SOD - 0.8 mg/100 g). The second factor was a high blood endotoxin level due to the glycerol injection. This possibility was examined by glycerol injection to rats that had developed endotoxin tolerance. The low survival rate (0-30%) of rats receiving a glycerol injection following preventive treatment with antioxidants as well as rats which had developed endotoxin tolerance (0-40%), excludes the possibility that the cause of death in the glycerol model resulting in fatal rhabdomyolysis is due to free radical formation or to a high and unneutralized blood level of endotoxin. PMID- 1298343 TI - [Possible effects of the influence of dynamic disorder of biological systems on characteristics of intramolecular mobility, determined by Mossbauer spectroscopy]. AB - A model for describing dynamic properties of proteins is proposed. The model involves the distribution over amplitudes and correlation times of intramolecular dynamics. It has been shown that distribution parameters and its temperature dependence have a great influence upon the values of experimental dynamic characteristics. Besides the discrepancy between the real and experimental temperature, dependence of characteristics on intramolecular dynamics can be observed. PMID- 1298344 TI - [Evaluation of the antioxidant and antiradical activities of substances and biological objects using iron-initiated chemiluminescence]. AB - Antioxidative and antiradical activity of the following typical inhibitors of free radical reactions were investigated in the model systems: ethanol, ionol, uric acid, superoxide dismutase, albumin. The antioxidative and antiradical activities of these inhibitors were shown to differ in various model systems. PMID- 1298345 TI - [Osmotic regulation of furosemide-sensitive K+ (86Rb+) transport in rat brain synaptosomes]. AB - In the rat brain synaptosomes the furosemide-sensitive component of 86Rb+ uptake constituted 30.8% of the total uptake in the medium containing 132 mM Na+. A decrease in the medium tonicity from 310 to 230 mOsm increased the rate of 86Rb+ uptake from 2.38 +/- 0.58 to 7.12 +/- 0.52 nMoles/mg of protein/min. PMID- 1298346 TI - [A physical model of gravitational erythrocyte sedimentation]. AB - A model of erythrocyte sedimentation under gravity is proposed. The model is based on two-phase description of the blood and it involves a kinetic equation of erythrocyte aggregation. A method of characteristics is employed for analysing the physical pattern of sedimentation for different hematocrit. An approximate decision for trajectory of the interface between pure plasma and low-located region of the erythrocyte suspension is obtained. By utilizing this decision the simple coefficient of the erythrocyte aggregation ability calculated in terms of hematocrit and erythrocyte sedimentation rate is possible. PMID- 1298347 TI - [Bifurcation analysis of a mathematical model of the interaction of cytotoxic lymphocytes with tumor cells. The effect of immunologic amplification of tumor growth and its interconnection with other "anomolous" phenomena of oncoimmunology]. AB - Mathematical model of the immune response of the cytotoxic lymphocytes to the nonexponentially growing immunogenic tumour has been studied. Local and global biffurcations for realistic values of the parameters were determined. The connection of the oncoimmunological "anomalous" phenomena (immunostimulation of tumour growth, "sneaking through" of tumour, formation of the tumour "dormant" state) has been shown. The probability of manifestation of these effects in vivo was estimated. PMID- 1298348 TI - [Dependence of the nerve pulse generation threshold on the ability of forming an input signal based on the Hodgkin-Huxley model]. AB - Different methods of definition of the threshold of the action potential (AP) generation were considered. It was established that the threshold defined as a difference between the critical value of the membrane depolarization and the resting potential was practically independent of the value and duration of an input signal which was given as a stepped function. It was shown that the critical values of the membrane depolarization could be defined by the point of bend, as well as by the point of maximum of the curve curvature on the frontal part of AP. PMID- 1298349 TI - [Surface tension of diluted solutions of human tears in the normal state and in various types of eye pathology]. AB - It is shown that the measurement of diluted solutions surface tension of normal tears and tears at different eye pathologies (cataract, glaucoma before and after operation) gave identical results. It is interpreted as a normal function of the lacrimal gland at these pathologies. PMID- 1298350 TI - [Evaluation of the possibilities of modeling biological tissues by the Focker Planck and Gui-Chapman joint system of equations]. AB - When describing the galvanic effect on biological tissues ion diffusion was taken into account in the Focker-Planck model, in the Gui-Chapman model account was taken of bolzman ion distribution while solving Poisson equation. To specify the models joint solution of these equations ought to be carried out. However, the equation system of Focker-Planck and Gui-Chapman proved to be reestimated, and therefore one can speak only about quasisolution as a solution of an incorrectly stated problem. PMID- 1298351 TI - [Connection of the carbon isotopic composition of human hair with its functional state]. AB - Temporal variations of carbon isotope composition of hair taken from faces of three men with different health state were studied. Drastic enrichment (up to 20%) of hair carbon in heavy isotope, as compared to the basic line reflecting background isotope variations was discovered in one of the men under test. This enrichment correlated with his worsened state of health. Then carbon isotope composition of hair returned to the background level. Probable explanation of this correlation was suggested in terms of earlier described mechanism of carbon isotope fractionation in a living cell. PMID- 1298353 TI - [A biomechanical invariant of automated movement]. AB - Trained arm movements and two-link arm dynamics and control of arm movements model are investigated. It is found that for these movements the component of the movements energy dissipations in the control force potential is invariable during the outer force actions. PMID- 1298352 TI - [Variability of some isotopic characteristics of carbon in man]. AB - Variability of some carbon isotope characteristics in man (i.e. carbon isotope composition of hair, blood, nails, expiratory carbon dioxide) was studied. Slow (with the period about 20-30 days) oscillations near some average level with a variable amplitude were observed in the isotope composition of the hair carbon. The maximum deviation from the mean level in one person tested was 6%. In the isotope composition of carbon dioxide respired under physical load and under conditions of aerobic metabolism during short periods (up to 15 minutes) there were also found significant variations from the mean level, the maximal ones being 6/1000. An attempt was made to explain the changes observed of isotope characteristics in terms of the principal carbon isotope fractionation cell model proposed earlier. PMID- 1298354 TI - [Mechanical energy expenditure on human movement and the anthropomorphic mechanism]. AB - Mechanical energy expenditures of the man and anthropomorphic locomotion machine during movement are compared theoretically. Sources of the mechanical energy affecting movement of human's lower extremity are modelled by 8 muscles, 3 of which are the two-joint muscles. The model of the lower extremity of anthropomorphic locomotion machine is moved by joint moments. It was shown that in the same movement the model of the human lower extremity can spend less mechanical energy than that of the model of the anthropomorphic locomotion machine. It is caused by the presence of two-joint muscles in the first model. Such an economy of mechanical energy expenditures realized by the two-joint muscle is possible at simultaneous execution of three conditions: 1) signs of the muscle powers, which are produced by that muscle at both joints, are opposite; 2) moments produced by that muscle at each of both joints have the same direction with the joint moments at these joints; 3) one-joint antagonistic muscles are not active. An expression which makes it possible to estimate the mechanical energy savings by the two-joint muscles during humans' movement was developed. PMID- 1298355 TI - Sensitive method for the determination of phenytoin in plasma, and phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin in urine by high-performance liquid chromatography. AB - An isocratic high-performance liquid chromatographic method is described for the quantitative analysis of phenytoin (PHT) in plasma and both phenytoin and its main metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) in urine. Following ethyl acetate (plasma) and Extrelut-1 (urine) extraction, samples are analysed by means of a reversed-phase column (Nova-Pak C18), using a mobile phase consisting of methanol-water-tetrahydrofuran (40:60:4, v/v/v) with UV detection at 230 nm. The chromatography is complete in 10 min and the results show good precision (RSD 1.23-4.49%) and sensitivity for a linear range of 0.4-4.0 micrograms ml-1 for PHT in plasma, 0.1-1.0 microgram ml-1 for PHT in urine and 0.1-1.2 microgram ml-1 for p-HPPH in urine. The results indicate the method to be suitable for pharmacokinetic studies. PMID- 1298356 TI - Planar chromatography: current status and future perspectives in pharmaceutical analysis--I. Applicability, quantitation and validation. AB - The most important features of capillary action planar chromatographic methods are summarized. Certain properties such as ease in operation, sensitivity to experimental conditions, stationary and mobile phase selection, phase system optimization, separation efficiency and detection possibilities are discussed only briefly. Other aspects such as the applicability of planar chromatographic methods in pharmaceutical analysis, quantitation and validation are considered in more detail. The advantages and limitations of different evaluation techniques (visual comparison, spot elution techniques and in situ densitometry) are also discussed. Validation steps specific to planar chromatographic methods are emphasized. PMID- 1298357 TI - Planar chromatography: current status and future perspectives in pharmaceutical analysis (short review)--II. Special techniques and future perspectives in planar chromatography. AB - The state of the art of various special analytical planar chromatographic methods is summarized especially for forced-flow planar chromatography (FFPC), overpressured-layer chromatography (OPLC) and rotation planar chromatography (RPC) as well as for the automated multiple development (AMD) technique. The connection between analytical planar and column liquid chromatographic methods and the identification of separated compounds with chromatographic and spectroscopic data are summarized. Some aspects of future perspectives, such as parallel connected multi-layer FFPC and long distance OPLC (LD-OPLC) are given. A combination of OPLC with the AMD method is predicted as the method of the future. Strategies using FFPC techniques are suggested in the form of a flow chart. PMID- 1298358 TI - Use of TLC and multivariate mathematical statistical methods to study the interaction of monoamine oxidase inhibitory drugs with amino acids. AB - The interaction of 17 monoamine oxidase inhibitory drugs (propargylamine derivatives) with amino acids was studied by charge-transfer chromatography. The data set was evaluated by principal component analysis (PCA). To assess the effect of the information loss caused by normalization, PCA was separately carried out on the covariance and on the correlation matrix. The strength and selectivity of interaction was separated by the spectral mapping technique. Calculation proved that the amino group of the drugs interacted with the second carboxyl group of dicarboxylic amino acids, and that the interaction was of electrostatic character. This finding made probable the direct interaction between the drugs and the target enzyme or enzymes. The results of both PCA methods were similar. However, coordinates of the spectral map showed only slight correlation with the corresponding coordinates of the two-dimensional nonlinear maps proving the different information content of the methods. PMID- 1298359 TI - Analysis of flavonoids by MECC with ultraviolet diode array detection. PMID- 1298360 TI - pH measurements in acetonitrile-water mixtures by use of a glass electrode. PMID- 1298361 TI - Polarographic determination of doxorubicin and daunorubicin in pharmaceutical preparations and biological media. PMID- 1298362 TI - Colorimetric methods for the assay of carbimazole in drug formulations using dichromate and molybdate. PMID- 1298363 TI - The use of fluorescamine (Fluram) in fluorimetric trace analysis of primary amines of pharmaceutical and biological interest. PMID- 1298364 TI - Determination of ethanol in biological samples by head-space gas chromatography. PMID- 1298365 TI - Simultaneous determination of acetylsalicylic, salicylic, ascorbic and dehydroascorbic acid by HPLC. PMID- 1298366 TI - Rapid liquid chromatography of terpenes in Ginkgo biloba L. extracts and products. PMID- 1298367 TI - Densitometric evaluation of spiraeoside after derivatization in flowers of Filipendula ulmaria (L.) Maxim. PMID- 1298368 TI - Reversed-phase HPTLC densitometric evaluation of fraxin in Fraxinus excelsior leaves. PMID- 1298369 TI - Thin-layer chromatographic analysis of proanthocyanidins from Ribes nigrum leaves. PMID- 1298370 TI - Comparative bioavailability of verapamil from rapidly absorbed and slow release preparations. PMID- 1298371 TI - Tablet dissolution parameters: a statistical evaluation. PMID- 1298372 TI - Selectivity manipulation in micellar electrokinetic chromatography. AB - Micellar electrokinetic chromatography (MEKC) permits the separation of electrically neutral analytes by chromatographic principles in a capillary electrophoresis system. The most effective way to obtain high resolution in MEKC is to increase the separation factor, as in conventional chromatography. The separation factor in MEKC depends on the molecular structure of the micelle and hence on the surfactant used, the pH of solution, and the nature of any additives to the micellar solution. The hydrophilic moieties of surfactant molecules generally affect selectivity more than do the hydrophobic moieties. Chiral surfactants enable the enantiomeric separation of mixtures of chiral solutes to be achieved. Mixed micelles consisting of ionic and nonionic surfactants display different selectivity from that of single ionic micelles. Additives such as cyclodextrins, ion-pair reagents, urea, organic solvents and metals can also serve as useful modifiers of the micellar solution for improving separation. In particular, cyclodextrins are useful for the separation of aromatic isomers and enantiomers. A general introductory guide to the design of successful separations by MEKC is proposed, based primarily on the author's work. PMID- 1298373 TI - Determination of ascorbic acid and isoascorbic acid by capillary zone electrophoresis: application to fruit juices and to a pharmaceutical formulation. AB - Capillary zone electrophoresis was applied to the determination of ascorbic and isoascorbic acid, analysing the various parameters of influence such as the separation voltage, the buffer pH and concentration, the type of separation capillary or the loading conditions. Both analytes could be adequately determined within 5 min. The proposed method uses a 20 cm x 25 microns i.d. coated column, 0.1 M phosphate buffer pH 5.0, 8 kV separation voltage and light absorption detection at 265 nm. Linear calibration curves were obtained in the 0-1 mg mi-1 range, with detection limits of 0.5 micrograms ml-1. This method proved to be very rapid, simple and practical for the qualitative and quantitative determination of ascorbic acid in lemon and orange juices, as well as in a commercially available pharmaceutical formulation. PMID- 1298374 TI - The determination of the geometric isomers and related impurities of dothiepin in a pharmaceutical preparation by capillary electrophoresis. AB - The application of capillary zone electrophoresis in the assay of the tricyclic antidepressant drug, dothiepin, in tablets is discussed. The method developed for dothiepin which exists as the cis- and trans-isomers and contains two major related impurities, an 11-oxo compound and a propanamine, utilizes inclusion complexation with beta-cyclodextrin. For optimization of the method the structured procedure of factorial design was used; the electrolyte solution was 50 mM disodium hydrogen phosphate with 10 mM beta-cyclodextrin-propan-1-ol(90:10, v/v). Good precision (RSD = 1.06%, n = 6), linearity (y = 26.84x + 2.25), and correlation (r = 0.999, n = 7) was obtained for trans-dothiepin. The reproducibility of tablet extraction was also acceptable (RSD = 0.77%, n = 6); the recovery of the trans-isomer was 98% (w/w) and the level of cis-isomer in tablets of dothiepin (75 mg) was 5.58% (w/w). PMID- 1298375 TI - The automation of dissolution testing of solid oral dosage forms. AB - Dissolution testing of solid oral dosage forms plays a very important part both in the development of new products and in quality control. A fully automated system for dissolution testing known as AUTO DISS is presented and its components are described. On-line determination of active ingredient concentration is possible with the aid of an integrated automatic sampler in combination with various measuring instruments (UV-vis spectrometry, liquid chromatography and flow injection analysis). The suitability of the system is demonstrated by determination of the dissolution of brotizolam from tablets by FIA and of bepafant from capsules by diode-array spectroscopy. PMID- 1298376 TI - The use of microdialysis for the determination of plasma protein binding of drugs. AB - Microdialysis sampling was used for the determination of the protein binding and the free therapeutic drug concentration of drugs in plasma in vitro. Several drugs with varying extent of protein binding and for which the plasma monitoring is important were studied. To mimic the in vivo situation, an artificial blood vessel was constructed and filled with spiked plasma circulating at the flow rate of human blood at 37 degrees C. The microdialysis probe (16 mm membrane length, 20000 MW cut off) was placed in the vessel and perfused with 0.9% NaCl at 5 microliters min-1. Dialysates were collected every 10 min and were analysed by reversed-phase LC with UV detection. The free concentration of the drug was calculated by correcting the concentration in the dialysate for the recovery of the probe, which was also determined in the artificial blood vessel after the experiment. The data confirm that microdialysis is a valid alternative technique for the determination of protein binding or free therapeutic plasma concentration of drugs on a comparative basis. Reference to literature values indicates that the results of the proposed method correspond reasonably well with accepted values. PMID- 1298377 TI - Determination of compounds with anticholinesterase activity in commercial drugs by a new enzyme sensor. AB - A suitable enzyme sensor for the analysis of anticholinesterase compounds of pharmaceutical interest is described. It is based on the competitive inhibiting properties of these compounds on the enzyme butyrylcholinesterase and it is constituted by a hydrogen peroxide amperometric electrode modified by a superimposed Nylon membrane containing two chemically immobilized biological mediators (butyrylcholinesterase and choline oxidase). Some applications to the analysis of several pharmaceutical forms containing different compounds showing anticholinesterase activity are also reported and evaluated. PMID- 1298378 TI - Analytical comparison of an enzyme-amperometric method for chlorocresol determination in ointments with colorimetry and liquid chromatography. AB - The direct determination of chlorocresol in n-hexane extracts of commercial ointments was successfully performed using an enzyme-amperometric probe for analysis of phenols and working in previously characterized and optimized non aqueous solvents. The analytical data obtained were compared with those found by using classical HPLC or chemical spectrophotometric method for determination of phenols. PMID- 1298379 TI - PVC membrane electrode without inner reference solution for the direct determination of ephedrine in pharmaceutical preparations. AB - A PVC membrane electrode, without inner reference solution, based on an ion association extraction system responding to ephedrine is described. It incorporates an ephedrine-tetrakis (4-chlorophenyl)borate ion-pair complex in 2 nitrophenyloctyl ether. The prepared electrode exhibits a near Nernstian response (57.5 mV per decade) over the concentration range of 2 x 10(-5)-10(-1) M ephedrine in solutions of pH 2.5-9. The reproducibility of the electrode potentials were +/- 1 mV by day during at least 6 months. Response time was about 6 s for ephedrine concentrations between 10(-5) and 10(-1) M. Determinations of ephedrine in pharmaceutical preparations (tablets, nasal drops and syrups) by direct potentiometry gave an average recovery of 99.1% (w/w) and a mean standard deviation of 1.9% (w/w). PMID- 1298380 TI - Electrochemical behaviour of tizanidine at solid electrodes. AB - The electrochemical behaviour of tizanidine [5-chloro(delta-2-imidazolinyl-2 amino)-4-benzothiadiazole-2,1,3], a centrally-active skeletal muscle relaxant has been investigated in aqueous media at the carbon paste electrode (CPE). Cyclic voltammetry at different pH values, controlled potential coulometry and comparative studies on three structurally related molecules have permitted identification of the oxidation site of tizanidine and suggest possible oxidation products in acidic media. The electrochemical reduction at the CPE occurred in one irreversible step and the reduction product (diamine derivative) was detected and characterized on the positive going scan in cyclic voltammetry. Quantitative measurements of tizanidine within the range 2 x 10(-5) M and 1 x 10(-4) M have been realized at the CPE using the differential pulse technique. PMID- 1298381 TI - Novel flow injection analysis systems for drug analysis. AB - Flow injection analysis (FIA) has become a versatile tool for rapid and automated analyses. As its capabilities have increased, so have the complexity and operation of the apparatus. We have been investigating ways to simplify both the apparatus and the application of injection techniques. A novel cam-driven syringe pump and the development of sequential injection analysis (SIA) are reviewed, and some applications presented. Flow injection coulometric titrations are presented as a means to further alleviate reagent stability and calibration problems. These systems have potential for automatically carrying out many drug assays. PMID- 1298382 TI - The determination of the preservative, chlorocresol, in a pharmaceutical formulation by flow injection analysis. AB - A flow injection analysis (FIA) procedure is described for the determination of chlorocresol in a parenteral pharmaceutical formulation. The product is directly injected into a carrier stream of water and subsequently reacted with a reagent stream of nitrous acid. The resulting brown nitro-derivative is determined spectrophotometrically at 400 nm. The method has been validated and should be applicable to chlorocresol in other pharmaceutical products and to compounds containing a phenolic ring, assuming absence of matrix interference. PMID- 1298383 TI - Spectrophotometric determination of promazine with an oxidative column in FIA manifolds. AB - A simple flow-injection spectrophotometric method for the determination of promazine is described. The two proposed procedures are based on the oxidation of analyte with a manganese dioxide column. Concentrations of promazine in the ranges 2-20 and 1-6 are determined with a relative standard deviation of 1.0%. The injection rates are 62 and 80 samples h-1, respectively. The influence of foreign species and the determination of promazine in a pharmaceutical formulation are also reported. PMID- 1298384 TI - Liquid chromatographic separation of phenolic drugs using catalytic detection: comparison of an enzyme reactor and enzyme electrode. AB - A catalytic detection system based on the use of immobilized tyrosinase and two different transducers (photometric and electrochemical) is described. Comparison between tyrosinase immobilized in a packed-bed reactor and at the surface of a graphite electrode is discussed in terms of sensitivity in a flow injection system. The enzyme electrode configuration gives the highest sensitivity for the quantitation of dopamine. For the immobilized tyrosinase reactor with photometric detection the range for dopamine is linear up to 0.75 mM (136 micrograms ml-1) and the immobilized tyrosinase reactor with electrochemical detection and the tyrosinase electrode extends this dynamic range to 1 mM (181 micrograms ml-1). Liquid chromatographic separation and post-column detection using the tyrosinase electrode is shown for spiked samples of serum. PMID- 1298385 TI - The use of near infrared spectroscopy in the quality control laboratory of the pharmaceutical industry. AB - The suitability of NIR spectroscopy as an alternative to several compendial test methods is discussed. Using ampicillin trihydrate as an example it is demonstrated that eight quality criteria are controlled by recording the NIR spectrum of a batch sample and calculating its Conformity Index. PMID- 1298386 TI - Spectrofluorimetric determination of sulphonamides in pharmaceutical compounds and foods. AB - Spectrofluorimetry and room temperature photochemically-induced fluorescence (RTPF) have been applied to the determination of sulphacetamide (SAC), sulphaguanidine (SG) and sulphamethazine (SMT) in milk and pharmaceutical formulations. The methods are suitable for determining 0.02-0.10 micrograms ml of SAC, 0.10-0.50 micrograms ml of SG, and 0.40-1.00 micrograms of SMT. PMID- 1298387 TI - Fluorescence enhancement of two terpenes commonly present in essential oils. AB - The fluorescence spectra of anethole and eugenol dissolved in methanol-aqueous binary systems with the addition of alpha- and beta-cyclodextrin were studied. Observed enhancement of the fluorescence intensity is possibly due to the higher quantum yield of the cyclodextrin-hydrocarbon inclusion complexes. The measured fluorescence intensities for eugenol and anethole in the presence of alpha- and beta-cyclodextrin were processed using principal component analysis. The results obtained suggest 1:1 and 2:1 complexation, as confirmed by a double reciprocal plot for terpenes complexed to cyclodextrins. In both cases (anethole and eugenol) detection limits were improved after addition of cyclodextrins. This phenomenon can be applied for improvement of direct fluorescence and HPLC fluorescence assays. PMID- 1298388 TI - A biotin-avidin based screening test for methamphetamine in urine. AB - A biotin-avidin based screening test for methamphetamine in urine samples has been developed. The assay method utilizes the immunoprecipitin reaction between an antibody to methamphetamine and a conjugate prepared by complexing avidin with a biotinyl amphetamine derivative. The rates of the immunoprecipitin reaction is monitored on the Beckman ARRAY 360 nephelometer. Methamphetamine inhibits the precipitin reaction, and the extent of inhibition allows the quantitation of methamphetamine in the urine samples. Using a cut-off value of 0.7 microgram ml 1, the assay correctly predicted 83 of 84 samples (98.8%) confirmed to be positive by GC-MS (> 500 ng ml-1). Of 59 GC-MS confirmed negative samples, 46 samples were found to be negative by this method as compared to 34 samples determined with the EMIT assay. Within-run and between-run relative standard deviations near the cut-off value were less than 4%. Cross-reactivity with amphetamine was < 7%. PMID- 1298389 TI - Analysis of mono-, di- and triglycerides in pharmaceutical excipients by capillary supercritical fluid chromatography. AB - Mono-, di- and triglycerides are important components of oils, fats and other natural products. Since in general fatty acids are mixtures and glycerol can be differently substituted, finger-prints of the composition are suitable for better characterization. Since capillary supercritical fluid chromatography (SFC) employing carbon dioxide as mobile phase is compatible with flame ionization detection, it is possible to analyse many solutes at trace levels. Supercritical carbon dioxide offers higher solute diffusivity compared with the inert carrier gas conventionally used in gas chromatography and has a lower viscosity than the liquid solvents used in HPLC. Thus, glycerides of fatty acids can be separated and eluted at a lower temperature and with shorter analysis time in SFC. In this study the analysis of mono-, di- and triglyceride mixtures in several pharmaceutical excipients is reported using capillary SFC. Quantitative analysis is possible on the basis of a response factor established for each analyte. The accuracy of the method and its advantages are demonstrated. PMID- 1298390 TI - Estimation of impurity profiles of drugs and related materials. Part 9: HPLC investigation of flumecinol. AB - Two HPLC systems have been developed for the investigation of flumecinol (3 trifluoromethyl-alpha-ethyl-benzhydrol). The reversed-phase system (LiChrosorb RP 18; methanol-water, 7:3, v/v) enables the isolation and identification of the impurities. The chiral system (Chiralcel OD; hexane-2-propanol, 98:2, v/v) separates the enantiomers of flumecinol and its impurities. The potential of spectral convolution in peak identification in HPLC impurity profiling is demonstrated by an example involving the identification of the 4'-methyl-analogue of flumecinol. PMID- 1298391 TI - Assessment of chromatographic peak purity of drugs by multivariate analysis of diode-array and mass spectrometric data. AB - Numerous multivariate chemometric approaches have been developed for LC-UV data acquired using a diode-array detector (DAD), but these methods have not been widely exploited for LC-MS data. Principal component analysis (PCA) and subsequent axis rotation within the reduced factor space are assessed for LC-DAD and LC-MS data as approaches for estimating the number of components (i.e. the rank of the data) under a single chromatographic peak for compounds whose UV spectra are very similar. Multivariate techniques for LC-DAD data are shown to suffer from inherent limitations of sensitivity for the minor components. The novel technique in LC-MS of plotting the rotated PCA data in two-dimensional factor space generates characteristic ion clusters, giving a visual criterion of peak purity. Single ion chromatograms produced subsequently confirm the profile of each coeluting component and give evidence of the degree of peak overlap. The application of this new chemometric technique to the detection of low levels of coeluting impurities by LC-MS is discussed as a novel approach for the validation of LC separations in pharmaceutical research and development. PMID- 1298392 TI - Liquid chromatography for the quantitative analysis of antibiotics--some applications using poly(styrene-divinylbenzene). AB - Problems arising from the microbiological assay of antibiotics are discussed. The existence of several systems to express the potency leads to confusion. The use of potency to express the content of bulk products can lead to difficulties in the interpretation of the content of pharmaceutical preparations. Such problems can be avoided if the content of antibiotics is expressed as percentage weight in weight. This involves the application of selective assay methods such as liquid chromatography. The reproducibility of liquid chromatography depends largely on the quality of the stationary phase. Use of poly(styrene-divinylbenzene) as the stationary phase can lead to good reproducibility as is reported for erythromycin and for the tetracyclines, of which minocycline is discussed as an example. PMID- 1298393 TI - Analysis of erythromycin estolate by liquid chromatography. AB - A method is described for the determination of erythromycin estolate by liquid chromatography. A C18 reversed-phase column (25 x 0.46 cm i.d.) was used with acetonitrile-tetrabutylammonium sulphate (pH 6.5, 0.2 M)-phosphate buffer (pH 6.5, 0.2 M)-water [x:5:5:(90-x), v/v/v/v] as mobile phase. The proportion of acetonitrile (x) has to be adapted to the type of stationary phase used. For RSil C18 LL 42.5% (v/v) was used. The column was heated at 35 degrees C, the flow rate was 1.5 ml min-1 and UV detection was performed at 215 nm. The main component, erythromycin A propionate, was separated from all other components which were present in commercial samples. The impurities most frequently observed were the propionate ester of erythromycin C and the amide N-propionyl-N-demethyl erythromycin A. Erythromycin A was shown to be present in specialties. PMID- 1298394 TI - Dependence of the retention of some barbituric acid derivatives on a porous graphitized carbon column on their physicochemical parameters. AB - The retentions of 45 barbituric acid derivatives were determined on a porous graphitized carbon column (PGC) in unbuffered methanol-water eluent mixtures at various organic phase concentrations and the retention data were correlated with the various hydrophobic and electronic parameters of barbituric acid derivatives. Each derivative showed symmetric peaks in each eluent proving the good separation characteristics of the PGC column without buffering the eluent. Significant linear correlations were found between the logk' value and the concentration of the organic mobile phase in the eluent. Stepwise regression analysis indicated that the retention of barbituric acid derivatives is mainly governed by the electronic parameters, and the lipophilicity of various substituents did not affect significantly the retention, although the eluents were typical reversed phase eluents. PMID- 1298395 TI - Multidrug assay method for antimalarials. AB - A general separation strategy, involving solid-phase extraction followed by reversed-phase ion-pairing HPLC with an organic counter ion for a set of 11 widely used antimalarial drugs and metabolites has been developed. The basis underlying the separation has been explored and work, including quantitative data, has been carried out on illustrative separations which form the basis of novel quantitative assays of groups of antimalarials which are relevant to current prophylaxis and treatment of malaria. PMID- 1298398 TI - Nadolol: high-pressure liquid chromatographic methods for assay, racemate composition and related compounds. AB - High-pressure liquid chromatographic (HPLC) methods have been developed for the determination of drug content, racemate A and related compounds in nadolol raw materials. The method for drug content and related substances resolved seven related compounds and several unknown impurities from the drug. The minimum quantifiable levels were 0.05% or less for four of the seven related compounds and 0.3% or less for the remainder. Total impurities in eight raw material samples ranged from 0.06 to 0.96% and assay levels ranged from 98.7 to 101.0%. The method was adapted for the determination of nadolol racemate A by a change in mobile phase composition. One raw material sample contained less than 40% of racemate A. Two samples which had a granular appearance were variable in racemate A content. The methods were adapted for the determination of drug and racemate A in nadolol tablets. Drug content in three tablet samples was between 96.2 and 98.4% and racemate A content was about 52%. PMID- 1298396 TI - HPLC analysis of imidazole antimycotic drugs in pharmaceutical formulations. AB - Reversed-phase HPLC on different column packing materials (Hypersil C-18, Spherisorb-CN, Chromspher-B) is used to obtain selective separations of imidazole antimycotic drugs, such as ketoconazole, clotrimazole, tioconazole, bifonazole, isoconazole, econazole, miconazole and fenticonazole. The use of a post-column on line photochemical reactor is shown to be useful for the enhancement of the sensitivity of the HPLC analysis with UV detection. The proposed HPLC methods are applied to the analysis of commercial dosage forms (creams) with solid-phase extraction (SPE) procedure, using a diol sorbent, being found to be a convenient technique for the sample preparation giving quantitative drug recovery. PMID- 1298399 TI - Indirect detection of anti-acetylcholinesterase compounds in microcolumn liquid chromatography using packed bed reactor with immobilized human red blood cell acetylcholinesterase and choline oxidase. AB - The inhibiting compounds were separated by micro-column liquid chromatography in the mobile phase containing the natural substrate acetylcholine. A home-made packed bed microbioreactor system containing immobilized enzyme acetylcholinesterase (ACHE) in human red blood cell membrane and choline oxidase (CHO) from alcaligenes was used for the post-column conversion of acetylcholine to hydrogen peroxide which was detected by an electrochemical detector. The inhibition effect of the solutes caused a decrease in the acetylcholinesterase activity, a decrease in the formation of hydrogen peroxide and also a decrease in the response corresponding to the concentration of the solutes. The rate of the enzyme regeneration was also recorded. The micro-system was compared with a conventional LC system comprising commercially prepared enzyme reactor. The stability of the enzymes is at least 3 weeks at ambient temperature. The limit of detection depends on biological activity of inhibition and for galanthamine was 1 pmol. PMID- 1298397 TI - Design of chiral LC separations for calcium antagonists on alpha 1-acid glycoprotein and ovomucoid columns. AB - Three chiral calcium antagonist drugs, gallopamil and two dihydropyridine derivatives, have been successfully separated within short retention times using both the alpha 1-acid glycoprotein chiral stationary phase (Chiral-AGP) and the ovomucoid column (Ultron ES-OVM). Aqueous buffer at defined pH is modified by the addition of an organic component, in order to modulate the retention properties of each system. Optimization of pH and organic modifier is carried out using the modified simplex method, with Kaiser's peak separation function as a criterion. The influence of pH and percentage of organic modifier on retention, selectivity, resolution and column performance are discussed for the two dihydropyridines analysed on Chiral-AGP and Ultron ES-OVM stationary phases. A new method is proposed as a new chiral system suitability test for these protein-based phases, utilizing a racemic mixture of closely eluting verapamil enantiomers as a probe. PMID- 1298400 TI - Determination of verapamil and norverapamil in human plasma by liquid chromatography: comparison between a liquid-liquid extraction procedure and an automated liquid-solid extraction method for sample preparation. AB - A conventional liquid-liquid extraction (LLE) procedure with high-performance liquid chromatography (HPLC) has been developed for the determination of verapamil and its main metabolite, norverapamil, in plasma. After addition of the internal standard, plasma samples were basified with phosphate buffer (pH 9.0) and extracted with a mixture of cyclohexane-dichloromethane. After centrifugation, the organic layer was separated and the analytes were extracted back into a 0.1 N sulphuric acid solution containing 2-aminoheptane. An aliquot of this aqueous phase was then injected directly onto the HPLC column. This LLE procedure has been compared with an automated liquid-solid extraction (LSE) method that has been developed in parallel. Good linearity was obtained using both extraction methods. The absolute recoveries for the two analytes were ca 95% with the automated LSE procedure and slightly lower (ca 84%) for the LLE method. The automated method gives better results with respect to detectability and precision, but the LLE procedure is simpler to develop, requires much less expensive equipment, and remains a useful alternative when the number of samples to be analysed is limited. PMID- 1298401 TI - Analysis of cocaine, benzoylecgonine, ecgonine methyl ester, ethylcocaine and norcocaine in human urine using HPLC with post-column ion-pair extraction and fluorescence detection. AB - The measurement of cocaine and its major metabolites has been achieved by an HPLC method that compensates for their different solubilities and detection properties. Although ecgonine methyl ester is a major metabolite it is generally not measured by HPLC because it is poorly detectable by UV, and its water solubility makes recovery from urine difficult. Using modified solid-phase extraction procedures recoveries of 85% for ecgonine methyl ester, 97% for cocaine, 106% for benzoylecgonine and 80% for ethylcocaine have been obtained from urine. Increased chromatographic retention and detection sensitivity has been obtained by formation of the t-butyldimethylsilyl derivative of ecgonine methyl ester which was found to be stable in the HPLC mobile phase for at least 1 week. Alkylation of norcocaine and benzoylecgonine has improved their detection sensitivity and also chromatographic resolution. All calibrations were linear over the range 200-1000 ng ml-1 in urine with correlation coefficients > 0.99. PMID- 1298402 TI - Solid-phase extraction and optimized separation of doxorubicin, epirubicin and their metabolites using reversed-phase high-performance liquid chromatography. AB - A reversed-phase isocratic high-performance liquid chromatographic method is described in which a formal structured procedure was applied to predict the mobile phase composition giving optimal baseline resolution of the clinically important anticancer agents doxorubicin and 4'-epidoxorubicin (epirubicin), their principal metabolites, and daunorubicin (internal standard). These formal statistical procedures included the simultaneous techniques of solvent selectivity triangle and factorial design for range-finding preliminary studies, followed by use of the modified simplex, a sequential procedure. These were used to select the parameters of organic modifier, buffer strength and pH necessary for use with a Spherisorb ODS 1 column, to achieve optimal separation of eight anthracycline solutes. Ultraviolet and fluorescence detection was used (lambda ex = 254 nm, lambda em = 560 nm), and the latter gave a low detection limit for doxorubicin in serum of 1 ng ml-1. The optimal mobile phase composition was determined to be acetonitrile-0.06 M Na2 HPO4 containing 0.05% (v/v) triethylamine adjusted to pH 4.6 with 0.03 M citric acid (35:65, v/v). A solid phase extraction method was developed to enable the selective isolation of anthracyclines by adsorption onto C8 Bond-Elut cartridges, and is based on extraction of serum spiked with a mixture of the anthracycline solutes. The anthracyclines were eluted using acetonitrile-0.2 M Na2 HPO4 containing 0.05% (v/v) triethylamine adjusted to pH 3.6 with 0.1 M citric acid (67.5:32.5, v/v). Reproducible recoveries for doxorubicin (94 +/- 8%) and for epirubicin (96 +/- 8%) were obtained (n = 5). In particular, recoveries for the 7-deoxyaglycone metabolite (99%) were higher than other extraction methods cited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298403 TI - Determination of a renin inhibitor in plasma by solid-phase extraction using acetone as protein binding displacer followed by on-line high-performance liquid chromatography. AB - H 218/54 is a potent inhibitor of human renin activity (pIC50 = 8.3 at pH 6) and is therefore a potential agent for blood pressure reduction. This lipophilic compound is highly bound to plasma proteins, e.g. 99.7% in rats and 99.6% in humans. For pharmacokinetic studies, a quantitative assay for 3H-H 218/54 in plasma has been developed. On top of an AASP phenyl solid-phase cartridge 70 microliters of rat plasma or 1 ml of cynomolgus plasma was mixed with 200 microliters of water containing 20% acetone. The acetone displaced the substance from plasma proteins without precipitation of the sample and clogging of the extraction column. The mixture was passed through the cartridge, which adsorbed 3H-H 218/54. The cartridge was placed in an AASP autosampler connected to a reversed-phase LC system, with a Vydac C-18 column and CH3CN-H2O-TFA (60:40:0.1, v/v/v) as mobile phase. The effluent from the separation column was collected in fractions for radioactivity counting. Recovery, as measured after adding various amounts of tritium-labelled H 218/54 to blank plasma followed by repeated analysis of the samples, was close to 100% with relative standard deviations between 1.4 and 3.0%. At the lowest level tested, 200 dpm per sample, the recovery was 120% with a relative standard deviation of only 10%. The sensitivity of the method will depend on the specific radioactivity of the dose given. PMID- 1298404 TI - Reversed-phase liquid chromatography of the opioid peptides. 3. Development of a microanalytical system for opioid peptides involving microbore liquid chromatography, post-column derivatization and laser-induced fluorescence detection. AB - A microanalytical system has been developed for the determination of peptides in small samples. Naphthalene-2,3-dicarboxaldehyde-beta-mercaptoethanol (NDA-BME) was used as the labelling reagent system as an alternative to NDA-cyanide (NDA CN) because of the faster labelling when CN was replaced by a thiol. The fluorescence characteristics of the NDA-thiol adducts, N-substituted 1 alkylthiobenz[f]isoindoles (TBIs), were found to be different from the previously described cyanobenz[f]isoindole (CBIs) adducts formed by the reaction of primary amines with NDA-CN. The excitation maximum of the TBI adducts was at 460 nm, which was closer to the 457.9 nm argon-ion laser line, than the 440-nm maximum of the CBI adduct. The limit of detection for leucine enkephalin was 36 fmol (S/N = 3) and linearity was proven for greater than 2 orders of magnitude, from 45 fmol to 9 pmol for an injection volume of 60 nl. The detectability was limited by the high background noise produced by the post-column derivatization system. The utility of the system was demonstrated for the analysis of methionine enkephalin and its potential oxidation products, using leucine enkephalin as a suitable internal standard. PMID- 1298405 TI - Determination of medroxyprogesterone acetate in serum by HPLC with peroxyoxalate chemiluminescence detection using a fluorogenic reagent, 4-(N,N dimethylaminosulphonyl)-7-hydrazino-2,1,3-benzoxadiazole. AB - The high-performance liquid chromatographic determination of medroxyprogesterone acetate (MPA) with peroxyoxalate chemiluminescence (PO-CL) detection is described. The spiked serum containing MPA was extracted on Bond-Elut C18 columns and derivatized with 4-(N,N-dimethylaminosulphonyl)-7-hydrazino-2,1,3 benzoxadiazole (DBD-H). The hydrazone of MPA with DBD-H was confirmed to be a mono-DBD-derivative. The reaction mixture was separated by direct injection onto a C18 analytical column, and quantified by PO-CL detection. The linear range of the standard curve, in serum, was 15.6-96.6 ng ml-1 with a detection limit of 9 ng ml-1 using only 100 microliters of serum, while the detection limit of standard MPA derivatized with DBD-H was 8.7 fmol per injection. The relative standard deviation of the method was 7.4% at 19.3 ng and 1.7% at 77.3 ng ml-1. PMID- 1298406 TI - Packed capillary liquid chromatography coupled to fluorescence detection: application to human blood samples for the determination of glutathione. AB - The present investigation analyses the potentials of capillary chromatography using packed fused silica capillaries filled with 5 microns RP-18 for the fluorescence determination of glutathione in human blood samples. Adaptation of conventional HPLC equipment for miniaturized chromatographic assays proved successful. Sample preparation was relatively simple, though care should be taken in sample handling. The thiolic compound mercaptoethanol was used as internal standard. Qualitative determinations were based on standard addition providing increased peak heights at identical retention times. Quantitative determinations gave linear calibration curves, with a standard glutathione recovery of 98.9% and an intra-assay reproducibility of 3.3%. The glutathione values measured appeared within the normal range of 0.9-1.7 mmol glutathione per litre of blood. PMID- 1298407 TI - Liquid chromatographic method for separation and determination of elaiophylin in biotechnology processes of salinomycin production. AB - An LC method for the quick and precise quantitative determination of elaiophylin in biotechnology processes of salinomycin production was prepared. A mobile phase of methanol 0.04 M diammonium hydrogen phosphate pH 6.0-ethyl acetate (55:35:10, v/v/v) and an elevated column temperature optimized the chromatography. Separation of elaiophylin was obtained in 4-6 min. Positive identification and peak purity of elaiophylin have been carried out by photodiode array (PDA) detection. An agreement between the PDA spectra of samples and the elaiophylin standard were obtained. PMID- 1298408 TI - Endocrinology of calcium metabolism in amphibians, with emphasis on the evolution of hypercalcemic regulation in tetrapods. AB - Amphibians are the most diverse group as regards the endocrinology of Ca homeostasis because in them only "true" parathyroid glands made first appearance but its involvement varies greatly according to their phyletic affinities and habitats. Presence of ultimobranchial gland, parathyroid and renal 25 hydroxyvitamin-D-1-hydroxylase enzyme in anurans represents their tetrapod pattern of Ca regulation. Among "higher" urodeles, both parathyroid and pituitary are involved in hypercalcemic regulation whereas in "lower" urodeles (some of them are "aparathyroid" too), pituitary alone appears to discharge this function. The latter situation is analogous to the fish. Apodans do possess ultimobranchial and parathyroid glands but the problem of their Ca metabolism has not yet been explored. This review deals exhaustively with the endocrinology of Ca metabolism in amphibians. Also, the evolution of hypercalcemic regulation in tetrapods will be discussed in the light of recent developments. PMID- 1298409 TI - Hermaphroditism in young mouse chimeras. AB - Among 23 5-day old mouse chimeras, 11 were sex chimeras. Four of them were hermaphrodites, six were males and one was female. In the gonads of three hermaphrodites fragments of ovarian tissue were very small. Growing oocytes were observed not only in ovotestes but also in testes. The course of transformation of ovotestes into testes is discussed. PMID- 1298410 TI - Reconstruction of midface bone defects with vitallium micromesh. AB - Complex midface defects following trauma and tumor resection present a challenging problem for maxillofacial surgeons. Regardless of the cause of these defects, restoration of accurate contour is essential to achieve both proper function and cosmetically acceptable appearance. Traditionally, bone grafts have been the preferred method of reconstruction. We present the first report of the use of Vitallium micromesh in reconstruction of midface bone and cartilaginous defects in 3 patients. In 1 patient, bone loss resulted from trauma; in the other 2, loss was due to tumor resection. In all 3 patients, Vitallium micromesh was used successfully as a replacement for the bony skeleton without morbidity or complications. Use of this material is contingent on its rigid fixation. We do not recommend use of this technique in the absence of rigid fixation. PMID- 1298411 TI - Soft-tissue alterations associated with acute, extended open reduction and internal fixation or orbital fractures. AB - Soft-tissue alterations associated with radical degloving of the overlying soft tissues during extended open reduction and rigid internal fixation of facial fractures involving 51 orbits in 36 patients were studied. In all patients, the blepharoplasty skin muscle flap incision was employed in conjunction with, as necessary, a gingivobuccal sulcus and coronary incisions. Patients were evaluated between 6 and 20 months after surgery. Physical examination and standardized photographs were used for assessment. Ectropion developed in 2 lids (4%), and 10 lids (20%) had increased scleral show. Thirteen of the 51 lids (25%) revealed lateral canthal displacement; all 13 lids underwent canthal stripping. Cheek pad displacement developed in 8 patients (22%), all of whom had complete maxillary degloving without soft-tissue resuspension. No patient had frontal nerve palsy. Depression in the temporal area was noted in all patients in whom the temporalis was mobilized. Remote incisions and soft-tissue degloving used for extended open reduction and internal fixation are associated with morbidity that can be minimized by meticulous technique and soft-tissue repositioning at closure. PMID- 1298412 TI - Influence of the maxillary canine on mandibular fracture. AB - The length of the root of the mandibular canine tooth has been considered by many authors as being a source of weakness in the mandible. It has also been suggested that a direct blow or a bending force around this tooth can result in traumatic injury. We advance a theory that implicates the maxillary canine tooth as directly contributing to the mandibular canine region fracture pattern. PMID- 1298413 TI - Neurological deterioration after lumbar cerebrospinal fluid drainage. AB - Large-bore lumbar spinal fluid drainage is used frequently as part of the preoperative and intraoperative management of patients undergoing cranial base tumor resection. Such drainage allows displacement of the brain with minimal force, thereby potentially decreasing retraction damage to it. We document 2 patients in whom serious complications resulted from lumbar drainage systems. These patients deteriorated into a coma state following cerebrospinal fluid (CSF) drainage. Reinfusion of synthetic CSF solutions caused a brisk return to normal neurological status. These plus other potential complications associated with lumbar drainage, such as persistent CSF leaks into the back and soft-tissue nerve root injury, warranted abandoning the lumbar cistern drainage route of CSF drainage in favor of drainage directly from the intracranial compartment. Depending on the particular operation performed, drainage of CSF near the cribriform plate, the suprachiasmatic cistern, or from the sylvian fissure may be effective sites for CSF drainage. Unlike lumbar drainage, intracranial CSF drainage does not have the added risk of promoting cerebral herniation. PMID- 1298414 TI - Total temporomandibular joint reconstruction with a Delrin titanium implant. AB - Numerous alloplastic materials have been used for partial or total reconstruction of the temporomandibular joint in patients with fibrous or bony ankylosis, severe degenerative joint disease, or traumatic deformity, and for reconstruction following tumor resection and corrective surgery following multiple arthroplasties. We have had initial success with the use of a polyoxymethylene (Delrin) condylar head affixed to a pure titanium mesh for these reconstructive procedures. This versatile prosthesis does not require use of a separate glenoid fossa prosthesis. The surgical technique, as well as a historical perspective on alloplastic total joint prostheses used to date, is described in several patients. PMID- 1298415 TI - Prevention of cranial reossification after surgical craniectomy. AB - An experimental study in rats was designed to see whether the pericranium, used as a graft over the dura, can prevent or delay osseous reunion after craniectomy. A 10 x 3-mm section of the frontal and parietal bones, including the coronal suture line, was resected in 15 rats. Pericranium was then used as a free graft on one-half of the defect to cover the dura and separate it from the cut edges of the craniectomy. The other side acted as a control. All animals were killed 2 months after operation, the skull was removed, and any remaining bony defect on either side of the midline was revealed. The area of residual defect in 13 specimens was determined by statistical image analysis using the Oxford Modular Cataract Image Analysis System (Oxford, England) and Wilcoxon's rank sum test and showed a highly significant difference between the treated and the untreated sides (p = 0.002). PMID- 1298416 TI - The frontal tiara. AB - A technique for the construction of a frontal bar and a forehead plate as a single unit is described. This technique could be used in any procedure in which a frontal bandeau is advanced and the forehead needs to be remodeled. By using microscrew fixation, the bulkiness of miniplates and wires is eliminated. PMID- 1298417 TI - Bone grafting the orbital floor for posttraumatic defects. PMID- 1298418 TI - To shave or not to shave. PMID- 1298419 TI - Recipient vessels for microvascular transplants in patients with hemifacial microsomia. AB - Hemifacial microsomia is a developmental abnormality involving structures derived from the first and second branchial arches. Microvascular transplants are increasingly being used to improve facial contour in patients with this condition. We have reviewed 9 patients with this abnormality to determine which recipient vessels have been used. In 6 patients, the facial vessels were located and used for flap revascularization. In 3 patients, the facial vessels could not be identified intraoperatively, and the occipital artery and a branch of the external jugular vein were used as recipient vessels. In this series of hemifacial microsomia patients, therefore, the facial vessels could not be located in 3 patients. We recommend that surgeons performing microsurgical transplants in cases of hemifacial microsomia be prepared to explore the external carotid and external jugular systems for recipient vessels. PMID- 1298420 TI - Effects of resorbable fixation on craniofacial skeletal growth: a pilot experimental study. AB - The effects of fixation composed of resorbable polymers on craniofacial development was investigated in an animal model. Fourteen rabbits had amalgam markers placed bilaterally at the lambdoid, coronal, and frontonasal sutures at 28 days of age. Seven animals (group I) were not plated and served as controls. The other 7 animals (group II) were fixed across the left coronal suture with a 4 hole, compressive resorbable plate. After 6 months, intermarker distances (growth) were measured radiographically, and the amount of fixation degradation was determined by extracted plate weights. Resorbable plating across the coronal suture resulted in local marker constriction adjacent to fixation. Compensatory lengthening of the distal aspect of the frontal bone occurred, however resulting in unaltered total cranionasal lengths compared with that of control animals. Plate degradation occurred with a mean decrease of 7% from their original weights. Molecular weight analysis of the plate differences, however, was not done. This initial study indicates that a large plate size and slow resorption properties of polymer fixation can have a similar restrictive effect on bone growth as that of metal fixation. Whether thinner plates or more rapidly resorbing polymers will permit normal growth in this animal model awaits further testing. PMID- 1298421 TI - Plate fixation of premaxillomaxillary suture and compensatory midfacial growth changes in the rabbit. AB - It has been suggested that rigid fixation of the developing craniofacial skeleton may lead to altered craniofacial growth. However, recent experimental studies have shown that microplate fixation of slow-growing calvarial sutures resulted in regional growth disturbances but had little effect on overall craniofacial growth. The present study was designed to assess the effects of microplate fixation of the more rapidly growing facial sutures on compensatory midfacial growth in the rabbit. Twenty-two 1.5-week-old rabbits were randomly divided into 2 groups: sham controls (n = 11) and animals with bilateral premaxillomaxillary suture fixation (n = 11). Fixation was accomplished using an intraoral approach, a 6-mm straight Luhr microplate, and two 2-mm long self-tapping screws across each suture. Serial lateral head radiographs were collected at 1.5, 3.5, 6, 12, and 18 weeks of age. Results revealed that by 3.5 weeks, animals with rigid fixation showed significantly shortened premaxillary lengths (p < 0.05), class III occlusal relationships, decreased midfacial heights, and abnormal palatocranial base angles compared with sham control animals. By 12 weeks of age, "catch-up" growth was evident in most dimensions in animals with fixation compared with shams. Gross examination of the cleaned and dried skulls revealed bony bridging across the premaxillomaxillary suture and osseous fracture lines extending superiorly from the site of screw fixation. Results demonstrated that rigid fixation of a rapidly growing facial suture did not impair long-term midfacial growth in the rabbit model and suggest that compensatory changes may have occurred at fracture lines from the self-tapping screws in these animals. PMID- 1298422 TI - Histological and radioisotopical analysis of the skull graft: an experimental study in rabbits. AB - The purpose of this study was to develop an experimental model in rabbits that would permit us to analyze skull reconstruction and enable the study of bone autografts, osteofacial flaps, and other materials. We use the rabbit model to study the early integration of the skull autograft and to demonstrate the relationship between radioisotopical and histological analyses. PMID- 1298423 TI - The serratus anterior free tissue transfer for craniofacial reconstruction. AB - The serratus anterior muscle was used as a free tissue transfer to reconstruct complex craniofacial defects in 5 patients. Serratus anterior muscle alone and serratus anterior muscle with rib were the transfers made. All flaps survived and scapular winging did not occur. The serratus anterior muscle has several advantages for the reconstruction of medium-sized craniofacial defects. Because of its position, a two-team approach is possible. It has a consistent pedicle anatomy and low donor site morbidity. It has a large caliber vessel and a long pedicle. When compared with the commonly employed rectus abdominis flap for moderate-sized defects, the serratus muscle offers greater versatility in design and has the option of incorporating bone and innervated muscle without increasing significant donor site morbidity. PMID- 1298425 TI - Chondromyxoid fibroma of the zygoma. AB - A case of chondromyxoid fibroma (CMF) involving the zygoma is presented. To our knowledge, this case report represents the first description of CMF involving an extragnathic site in the facial skeleton exclusive of the cranium. Total excision and immediate reconstruction were done with alloplastic material fixated with microplates and screws. PMID- 1298424 TI - The radial forearm flap in intraoral reconstruction after a pull-through operation. AB - Free fasciocutaneous forearm flaps, based on the radial artery, were used to replace the tissue defect caused by pull-through operations for cancer of the floor of the mouth in 11 patients. There was no total or partial flap failure. The greatest advantage of the method is that restriction of the tongue movement is less when compared with the results of other methods. The thin forearm flaps are adaptable and pliable. The newly developed lower alveolar crest and the sublingual sulcus make prosthetic rehabilitation possible. PMID- 1298426 TI - Mandibular joint dysfunction otalgia caused by a bomb explosion wave. AB - Four hundred ninety-five patients were exposed to bomb explosion waves in civilian and war areas during the Iraq/Iran conflict. These patients were referred to the Oral and Maxillofacial Surgery Clinic after complaining of temporomandibular joint dysfunction with otalgia. Treatment ranged from conservative measurement to active surgery. Generally, response was good. PMID- 1298427 TI - Rigid internal fixation of a displaced mandibular coronoid fracture. AB - A report of the open treatment of the extremely rare displaced coronoid fracture of the mandible is presented. The previously predicted but undocumented oblique submuscular fracture from the depth of the mandibular notch to a point immediately behind the distal end of the alveolar process allowed displacement to occur. Use of plate and screw fixation for this exceedingly unusual injury avoided maxillomandibular fixation and was of benefit to this seizure-prone patient. PMID- 1298428 TI - Repair of a skull defect by a split cranial bone graft. PMID- 1298430 TI - Antimicrobial treatment of peri-implant infections. AB - The purpose of this study was to investigate the possibility of antimicrobial treatment of peri-implant infections associated with a periodontitis-like subgingival microbiota. Nine partially or fully edentulous patients with titanium hollow cylinder implants were selected which showed loss of bone and probing depths > or = 5 mm on one or several implants after at least 6 months following installation. They also yielded subgingival microbial samples with > or = 10(6) CFU/ml, including > or = 20% gram-negative anaerobic bacteria. The treatment included mechanical cleaning, irrigation of all peri-implant pockets > 3 mm with 0.5% chlorhexidine and systemic antimicrobial therapy (1000 mg ornidazole for 10 consecutive days). After therapy, bleeding scores decreased immediately and, over a one-year observation period, remained significantly lower than before treatment. A significant gradual reduction in mean probing depths was detected over this one-year period; only one case showed no improvement of local probing depth. Microbiological parameters indicated an instantaneous quantitative and qualitative change following treatment. Subsequently, several of these parameters tended to shift back towards pretreatment values. In the second half of the observation period, however, this tendency was reversed, and levels significantly different from baseline were eventually established. This study demonstrated that treatment aiming at reducing the subgingival bacterial mass and suppressing the anaerobic segment had a beneficial effect in patients suffering from peri implantitis. PMID- 1298429 TI - Plaque-induced marginal tissue reactions of osseointegrated oral implants: a review of the literature. AB - An intimate contact between bone and titanium implants was first demonstrated in 1969, and since then the bone-implant interface of osseointegrated implants has been investigated extensively. However, investigations of the marginal tissues and the microflora associated with osseointegrated implants have almost exclusively been carried out over the last decade. This review covers the clinical, radiographic, histologic, and microbiologic studies of marginal tissues of osseointegrated oral implants. In general, successfully osseointegrated implants exhibit low amounts of plaque concomitant with the absence of marginal inflammation. However, plaque accumulation may cause inflammatory reactions around the implants, sometimes giving rise to mucosal hyperplasia. Apparently, keratinized mucosa is not a requisite for the maintenance of peri-implant health if oral hygiene is adequate, but the presence of peri-implant keratinized mucosa is generally advocated. Alveolar bone loss around successful implants is minimal, but significant focal loss may occur due to plaque-induced inflammation or perhaps repeatedly extensive implant load. The progression of plaque-induced alveolar bone loss of osseointegrated implants may be different from that of teeth. It is unknown whether simultaneous marginal inflammation and excessive implant load further increase the loss of alveolar bone height. Both the light microscopic and ultrastructural characteristics of marginal tissues of implants and teeth are similar except for a lack of root cementum with inserting gingival collagen fibers of implants. Clinical inflammatory reactions are histologically characterized by an increased number of inflammatory cells infiltrating the connective tissue. The scattered subgingival microbiota associated with osseointegrated implants surrounded by healthy or slightly inflamed marginal tissues is similar to that of teeth with healthy gingiva. The microbiota associated with implants affected by marginal inflammation and bone loss is complex and consists predominantly of gram-negative anaerobic rods; this, again, is a similarity to periodontal disease. PMID- 1298431 TI - Supracrestal circular collagen fiber network around osseointegrated nonsubmerged titanium implants. AB - Eight non-submerged titanium implant screws were placed in the first upper molar edentulous sites of monkeys and subsequently kept loaded with single crown prosthesis 1 month following implantation. The animals were killed after a further 14 months and specimens including implant and adjacent teeth were processed for light and electron microscopy. Histological pictures of all samples showed the neck and most of the screw body to be surrounded by new bone. The soft tissue surrounding the implant post included pocket epithelium and supra-crestal connective tissue displaying collagen fiber bundles comparable to gingival ligaments. These peri-implant collagen fiber bundles arose from the neighboring alveolar crest, root cementum of adjacent teeth or, superficially, from the epithelium and followed a circular array around the implant neck. PMID- 1298432 TI - Speech in connection with maxillary fixed prostheses on osseointegrated implants: a three-year follow-up study. AB - In 21 individuals, edentulous in the upper jaw, the speech function was evaluated. In an earlier study, registrations were made when the patients wore complete dentures in the upper jaw and 3-6 months after they had been treated with fixed prostheses on osseointegrated implants in the maxilla. These patients were re-examined after 3 years, as reported in this follow-up study. An expert group as well as a non-expert group participated in a perceptual analysis. Acoustic, audiological and cast analyses were performed. In addition, a questionnaire was filled in. The results indicated that, after initial phonetic problems, 94% of the individuals considered themselves free from speech problems at the 3-year follow-up. The patients' experience of the change of the s-sound corresponded well with the judgement of both the expert and the non-expert groups. Difficulties with pronouncing the s-sound were associated with decreased bite force, the number of occluding contacts, the frontal width of the fixed prosthesis and tenderness at palpation of the masticatory muscles. These oral functional factors will contribute to the s-sound production. PMID- 1298433 TI - Radiographic evaluation of crestal bone levels adjacent to nonsubmerged titanium implants. AB - Several parameters have been described to determine success or failure in long term evaluations of dental implants. One of these parameters is the observation of changes in peri-implant bone levels. Studies on submerged implants have analyzed the bone level changes in the pre- and post-loading phases. No such data exist for intentionally nonsubmerged implants. The purposes of this study were: (1) to test the applicability and reproducibility of a simple computer-assisted method in the evaluation of changes in peri-implant bone levels; (2) to establish a baseline for the longterm radiographic follow-up; and (3) to evaluate changes in crestal bone levels adjacent to nonsubmerged ITI implants between the 1-year and 2-year examination. Standardized periapical radiographs were obtained from 80 implants at the 1-year and 2-year follow-up examinations after their placement. The implants were located in different jaw areas of 55 patients and supported single crowns or short-span fixed partial dentures. For each implant, the distance from implant shoulder to first crestal bone contact (DIB) was measured at the proximal surfaces with a digitizer/computer assembly. Statistically significant greater mean DIB were found at the 1-year (baseline) evaluation for: (1) maxillary sites overall (4.10 x 1.02 mm (SD)) compared with mandibular sites overall (3.61 +/- 1.03 mm); (2) maxillary anterior sites (4.08 +/- 0.97 mm) compared with mandibular posterior sites (3.60 +/- 1.05 mm); and (3) maxillary posterior sites (4.13 +/- 1.12 mm) compared with mandibular posterior sites. No statistically significant changes in DIB occurred in any of the jaw locations between the 1-year and 2-year evaluations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298434 TI - The macroscopic, microscopic and spectrometric effects of various chemotherapeutic agents on the plasma-sprayed hydroxyapatite-coated implant surface. AB - The purpose of this research was to determine the nature of the residual hydroxyapatite (HA)-coated implant surface after treatment with various chemotherapeutic modalities, including: citric acid, chlorhexidine gluconate, hydrogen peroxide, tetracycline HCl, stannous fluoride, polymyxin B and a prototype plastic Cavitron tip. Implant surfaces were evaluated macroscopically, microscopically (scanning electron microscopy (SEM)) and spectrometrically (energy-dispersive spectrometry and X-ray diffraction). HA-substrate bond strength and dissolution testing was also performed for surfaces treated with a supersaturated citric acid solution. All treatments left either microscopic residues or a loss of surface roughness when viewed on SEM. A 30- to 60-s application of citric acid left a significantly greater coating thickness than all other treatments, whereas a 3-min application of citric acid removed significantly more HA than untreated controls. Significant changes in Ca/P ratios were seen with most treatments. The clinical significance of this phenomenon is not known. No treatments altered the crystallinity of the residual HA coating. A 1-min application of citric acid did not significantly alter the tensile bond strength of the coating to the substrate. The clinical significance of these findings is not known at present. However, when taken with results from previous studies, it appears that in treating the infected HA-coated implant surface, a 30 to 60-s application of citric acid (pH 1) may be beneficial in detoxifying the HA coating prior to regenerative procedures. Further in vitro and in vivo studies are necessary to evaluate the biological response to citric acid when used to detoxify the infected implant surface. PMID- 1298436 TI - G-proteins mediate inhibition and activation of Ca(2+)-induced exocytosis from SLO-permeabilized peptidergic nerve endings. AB - In SLO-permeabilized isolated nerve endings from the rat neurohypophysis, GTP, guanosine 5'[y-thio]triphosphate (GTPyS) and guanosine 5'(beta y imido]triphosphate (GMPPNP) inhibit the Ca(2+)-evoked vasopressin release. Pretreatment with pertussis toxin enhances the inhibitory effects of both GTP analogues. Omission of Mg2+ overcomes the effect of GMPPNP and reverses the inhibitory effect of GTP and GTPyS. In the absence of Mg2+, GTP and GTPyS now potentiate Ca(2+)-evoked secretion. PMID- 1298435 TI - Processing endopeptidase deficiency in neurohypophysial secretory granules of the diabetes insipidus (Brattleboro) rat. AB - The homozygote Brattleboro rat exhibits a hereditary diabetes insipidus due to a deficiency of vasopressin, the antidiuretic hormone. It has previously been shown that in this animal a single nucleotide deletion in the provasopressin gene leads to a mutant precursor with a C-terminal amino acid sequence different from that of the wild-type. However the N-terminal region including the hormone moiety, the processing signal as well as the first two-thirds of the neurophysin is entirely preserved and absence of maturation has to be explained by an additional cause. We show here that the neurohypophysis of the homozygote Brattleboro rat, in contrast to the adenohypophysis, displays a significant decrease in the Lys-Arg processing endopeptidase activity when compared to the heterozygote or the wild type Wistar. It is suggested that hypothalamic vasopressinergic neurons of the homozygote Brattleboro rat display a deficiency in the processing enzyme in contrast to the oxytocinergic neurons in which processing of prooxytocin is normal. PMID- 1298437 TI - The human placental transferrin receptor: reconstitution into liposomes and electron microscopy. AB - Human transferrin receptor was isolated from Triton X-100 solubilized placental plasma membranes by a rapid one-step chromatographic procedure based on immunoadsorption of the receptor-transferrin complex on anti-transferrin Sepharose and lectin-affinity on wheat germ agglutinin. Following exchange of Triton X-100 with CHAPS or n-octylglucoside, the purified receptor was incorporated into egg phosphatidylcholine liposomes upon detergent removal by dialysis (lipid/protein ratio 15:1 to 45:1 (w/w)). Reconstitution of the receptor was confirmed by trypsin cleavage to dissociate the large extracellular receptor domain from the liposomal membranes. Electron micrographs of the receptor-lipid recombinants negatively stained with sodium sillicotungstate, showed that the receptor molecules distributed very inhomogeneously on the liposomes, most receptors being clustered. Single copies of the receptor were seen as elongate structures (5 x 10 nm) oriented with their long axis parallel to the liposome surface and separated from this by a 2-3 nm gap. This result provides evidence for a narrow connecting link between the globular extracellular receptor domain and the membrane spanning segment. PMID- 1298438 TI - Processing and characterization of the low density lipoprotein receptor in the human colonic carcinoma cell subclone HT29-18: a potential pathway for delivering therapeutic drugs and genes. AB - Low density lipoprotein (LDL) processing has been investigated in the subcloned human colonic carcinoma cell line HT29-18. LDL binding at 4 degrees C was a saturable process in relation to time and LDL concentration. The Kd for LDL binding was 11 micrograms/ml. ApoE-free HDL3 or acetylated LDL did not significantly compete with 125I-LDL binding, up to 500 micrograms/ml. 125I-LDL binding was decreased by 70% in HT29-18 cells preincubated for 24 hours in culture medium containing 100 micrograms/ml unlabelled LDL. Ligand blotting studies performed on HT29-18 homogenates using colloidal gold labelled LDL indicated the presence of one autoradiographic band corresponding to an apparent molecular weight of 130 kDa, which is consistent with the previously reported molecular weight of the LDL receptor in human fibroblasts. At 37 degrees C, 125I LDL was actively internalized by HT29-18 cells and lysosomal degradation occurred as demonstrated by the inhibitory effect of chloroquine. LDL uptake and degradation by HT29-18 cells also resulted in a marked decrease in endogenous sterol synthesis. These data demonstrate that the HT29-18 human cancerous intestinal cells are able to specifically bind and internalize LDL, and that LDL processing results in down-regulation of sterol biosynthesis. Thus, intestinal epithelial cells possess specific LDL receptors that can be exploited to accomplish drug delivery and gene transfer via the receptor-mediated endocytosis pathway. PMID- 1298439 TI - Exo-endocytosis in isolated peptidergic nerve terminals occurs in the sub-second range. AB - Exo- and endocytotic processes induced by depolarization of isolated neurosecretory nerve terminals show a close temporal correlation, which suggests a short time of integration of the neurosecretory granule membrane with the plasma membrane. In order to determine minimal time requirements for exocytosis coupled endocytosis to occur, we have analyzed by electron microscopy uptake of horseradish peroxidase (HRP) as a fluid phase marker at the onset of depolarization. We have applied rapid mixing and sampling (quenched flow) to assess events in sub-second time periods after stimulation. A significant number of labelled endocytotic vacuoles was observed during the first second of depolarization. This number then further increased by a factor of about 2 (within 5 s) and 4 (within 50 s). Thus, as for exocytosis, the rate of endocytosis decreased considerably during prolonged stimulation. These data indicate i) that a substantial proportion of secretory granules undergoes exocytosis very shortly after stimulation, and ii) that, following exocytosis, the minimal time required for consecutive membrane retrieval is in the sub-second range. PMID- 1298440 TI - Pulse shape analysis of RBC micropore flow via new software for the cell transit analyser (CTA). AB - The Cell Transit Analyser (CTA) provides a means to rapidly measure the deformability of large numbers of individual cells. It combines many of the advantages of micropipette studies with the simplicity and speed of filtrometry methods by measuring the duration of each resistive pulse generated as a cell passes through one of 30 identical micropores in a membrane. However, in our opinion, the potential of the system is limited by the microcomputer and software supplied for data analysis. We have therefore written new software for a more powerful microcomputer to examine the shape of each resistive pulse rather than just the duration. Seven new parameters are derived, which provide additional information regarding the passage of cells through the pores. In particular, the contribution of the entry and exit phases of the cell transit are evident in the rise time and fall time of the pulses. The software is user-friendly and allows the analysis of each pulse to be reviewed, which aids understanding of the system and helps to avoid errors in interpreting the data. PMID- 1298441 TI - Development of viscoelasticity in heated hemoglobin solutions. AB - Several previous studies have shown that exposure of RBC to temperatures in the range 47 to 48.8 degrees C causes an irreversible alteration of RBC rheological properties; membrane elasticity and viscosity are both increased and greater pressure is required for RBC entry into pipettes. While it has been tacitly assumed that these rheologic alterations are membrane specific, no data on heat treated hemoglobin (Hb) solutions appear to exist. The present study was thus designed to evaluate the effects of heat-treatment (48.8 +/- 0.1 degrees C, 3 to 20 min) on the viscoelasticity of Hb solutions (30 to 45 g/100 ml) prepared from normal human RBC. Measurements of the viscous component (VC) and elastic component (EC) were made at 25 degrees C using Couette (GDM) and capillary (OCR D) rheometers; shear rates ranged from 1 to 200 s-1. All unheated Hb solutions were Newtonian and did not exhibit elasticity. However, after 3 min of heating, an elastic component was measurable. Both VC and EC increased with heating time in a power law fashion. VC continued to exhibit Newtonian behavior, whereas the magnitude of EC was an inverse function of shear rate and directly related to Hb concentration and treatment time. A relaxation function applied to our data suggests a first order reaction. These results indicate that both cytoplasmic and membrane viscoelasticity should be considered in order to fully comprehend the rheologic behavior of heat-treated RBC. PMID- 1298442 TI - Rheological aspects of mucin-containing solutions and saliva substitutes. AB - In this study rheological properties of aqueous solutions of mucin, albumin and mucin-albumin have been investigated in search for saliva substitutes. They were compared with commercially available saliva substitutes on the one hand and natural human saliva on the other hand. For the latter a few measurements on saliva are reported here in addition to previously reported measurements done in our laboratory. Proteins absorb at the interface and saliva proteins do so strongly and rapidly. Therefore rheological measurements were carried out on the interface and on the bulk underneath the layer. In both cases the flow curve and the complex viscosity was determined. The results show that specific mucin albumin solutions were rheologically similar to human whole saliva with respect to both bulk liquid and surface properties. The rheological properties of commercial saliva substitutes were essentially different from those of human saliva. It is concluded that mucin-albumin solutions have good perspectives as saliva substitutes. PMID- 1298443 TI - Cell-free plasma layer in cerebral microvessels. AB - Two diameters of vessel and red cell column in cerebral microvessels (> 29.8 microns in diameter) of cat were measured together with red cell velocity, using a two fluorescent tracer method. A fluorescein isothiocyanate (FITC)-labeled red cell was adopted as a flow tracer to measure the cell velocity with a dual window technique. Based on the fluorescence image, the red cell column diameter was measured. Plasma was stained with rhodamine-B isothiocyanate (RITC)-labeled dextran to measure the vessel diameter. The thickness of the cell-free plasma layer could be determined from the difference of the two diameters. The obtained thickness of the cell-free layer was not described by a simple function of vessel diameter or red cell velocity; it was dependent on the pseudo shear rate defined by the ratio of cell velocity to vessel radius. The layer thickness increased with a decrease in the pseudo shear rate. PMID- 1298444 TI - The mechanism of erythrocyte sedimentation in Westergren's examination. AB - The authors deduced the equation that describes the sedimentation of erythrocytes as the function of time, hematocrit, hemoglobin and some plasma protein concentrations and the citrate viscosity and density. This values served to describe plasma and erythrocyte density, plasma viscosity, erythrocyte aggregation and the influence of suspension concentration on the erythrocyte sedimentation rate. The influence of citrate on blood dilution (the reduction of hematocrit and plasma protein concentrations) was also considered. A good agreement between the observed and predicted values was obtained. PMID- 1298445 TI - Adsorption of bovine serum albumin onto glassy carbon in a Couette flow. Effect of shear rate on the adsorption kinetics and on the structure of the adsorbed proteic layer. AB - Adsorption of bovine serum albumin onto glassy carbon is investigated by analysing the time-variation of the double-layer capacitance recorded during the adsorption process. The effect of shear rate is investigated under laminar conditions in a Couette flow. Stationary and sinusoidally modulated values of the shear rate are imposed over the (0-200 s-1) range. The flow conditions are shown to play an essential role by markedly modifying the rate of all the steps (three at most) involved in the adsorption mechanism. Moreover, the structure of the adsorbed layers in the intermediate and final states are also strongly modified, an increase of the shear rate increasing the interaction between the protein and the electrode. Piezoelectric properties of albumin are invoked to account for the experimental results. PMID- 1298446 TI - A new rheometer with special features designed for bronchial mucus analysis in clinical practice. AB - Changes in production and in physico-chemical properties of bronchial mucus is a common denominator of many pulmonary diseases. A rheometer with innovative features aimed at bronchial mucus routine investigation in clinical practice at the bedside of the patient has been designed. Searle-type configuration with a coaxial cylinder sensor system and the Mooney-Ewart geometry has been adopted. Another new feature is that bob and cup are disposable. Dynamic viscoelasticity is calculated through a microprocessor with specific software and by means of a magnetic torque--motor electronically driven by the microprocessor. The self zeroing procedure and the autorange greatly simplify the measuring-cycle which is driven by only one switch. Data (eta and G') are automatically printed on paper. The whole measuring-cycle at the bedside of the patient takes 3-5 min, so that in 1h about 12 samples can be investigated. PMID- 1298448 TI - Unsteady flow of Casson fluids through the eccentric circular tube. AB - As a model of the flow through the false lumen of the dissecting aortic aneurysm, the starting and stopping flows of the Casson fluid through the eccentric circular tube are studied numerically. The calculations are performed by using the one-direction fully developed unsteady flow model. The calculation results show that the non-Newtonian property of the Casson fluid has the following two effects. One is the decrease in the flow rate through the false lumen, the other is the effect to strengthen the non-uniformity of the velocity distribution in the false lumen. Moreover, the calculations based on a triphasic waveform measured by McDonald are performed and the development of the dissecting aortic aneurysm is discussed on the basis of the calculated wall shear stress. PMID- 1298447 TI - Changes in mechanical properties with DMSO-induced differentiation of HL-60 cells. AB - We measured changes in the deformability of human promyelocytic leukemic (HL-60) cells induced to differentiate for 5-6 days along the granulocyte pathway by 1.25% dimethylsulfoxide (DMSO). Differentiation resulted in an approximately 90% reduction in the transit times of the cells through capillary-sized pores over a range of aspiration pressures. Cell volume, as measured by two methods, decreased by an average of 35%. To account for the contribution of the volume decrease to the decrease in transit time, the liquid drop model, developed to describe neutrophil deformability, was used to calculate an apparent viscosity of the cells during this deformation. The apparent viscosity of both uninduced and induced HL-60 cells was a function of aspiration pressure, and an approximately 80% reduction in viscosity occurred with induction, as determined by regression analysis. The deformation rate-dependent viscosities of the induced cells were between 65 and 240 Pa-sec, values similar to those measured for circulating neutrophils. To assess the role of polymerized actin in these viscosity changes, intracellular F-actin content was measured, and the effect of dihydrocytochalasin B (DHB), an agent that disrupts actin polymerization, was determined. Despite the significant decrease in cellular viscosity, F-actin content per cell volume did not change significantly after induced differentiation. Treatment with 3 and 30 microM DHB lowered cellular F-actin content in a dose-dependent manner in both uninduced and induced cells. Cellular viscosity of both uninduced and induced cells decreased sharply with 3 microM DHB treatment (85% and 76% respectively). 30 microM DHB treatment caused a further significant reduction in the viscosity of uninduced cells, but for induced cells the additional decrease in viscosity was not significant. These data indicate that reductions in both cell volume and intrinsic viscosity contribute to the increased deformability of HL-60 cells with DMSO-induced differentiation. However, changes in the concentration of F-actin cannot account for the decrease in cellular viscosity that occurs. PMID- 1298449 TI - Application of diffractometry and a linear image sensor to measurement of erythrocyte deformability. AB - We applied laser diffractometry and a linear image sensor to measurement of erythrocyte deformability to detect the light intensity pattern of the diffraction image. Deformability was evaluated as the deformability index (DI), calculated from the width and length of the diffraction pattern ellipse, estimated by the linear image sensor. With the erythrocytes under various shear stresses, the DI was linearly related to results by the geometric method (r = 0.996, p < 0.01). The coefficient of variance of DI at a shear stress of 236 dynes/cm2 was 0.2% (seven human blood samples), which was satisfactory for practical use. The DI was independent of the erythrocyte concentration in the range of 1.5 x 10(7)-5.0 x 10(7) cells/ml of suspension. Correlation between the DI and the logarithm of shear stress was linear in the range of 5 to 350 dynes/cm2 of shear stress in suspension media of different viscosities. Heat treatment, which decreased membrane flexibility, caused parallel reduction of the DI plotted against the logarithm of shear stress. The method was sensitive and gave reproducible results. It may be useful for clinical applications. PMID- 1298450 TI - A numerical simulation of intimal thickening under shear in arteries. AB - A model of intima thickening proposed by Friedman and his coworkers (1,2) is incorporated in our computer code to simulate the growth of intima under shear. The computer code is based on a finite volume method in a boundary-fitted coordinate system. It is found that the model yields an evenly-distributed thickening over a straight, smooth vessel wall. However, in a stenosed or a curved artery, thicker intima can be formed in preferential regions due to unevenly-distributed wall shear stresses. The results clearly demonstrate the correlations among the geometry, wall shear rate and the plaque localization in arteries. The model is applied to a straight artery with a stenosis or sinus, a smooth curved artery and a stenosed curved artery. The effects of stenosis/sinus and lumen curvature on the flows and the intimal thickening are studied. The simulation provides a numerical visualization of the intimal thickening in a dynamic way. PMID- 1298451 TI - On transport of suspended particulates in tube flow. AB - Blood cells suspended in shear flows exhibit much larger dispersive motions than those predicted by the Stokes-Einstein formula for Brownian diffusion. The lateral migration and the erratic motions of the 8 microns red blood cells (RBC) is thought to be analogous to a diffusive process. It is shown that the often cited convective-diffusion theory may not be an adequate model for describing the transverse migration of suspended cells in blood flow. A comprehensive review of both the classical theory and of contemporary work in particle transport is presented, with particular emphasis on low Reynolds number tube flows. The mechanisms of Taylor dispersion, the effects of Brownian perturbations on translational and rotational motions of the suspended particles in shear fields, and the influence of integratable and chaotic advections, are individually examined. The classical experiment by Segre and Silberberg (1962) lead us to believe that particle hydrodynamics may play an important role in transverse migrations. In this light, we have further examined the hydrodynamic aspects of the so-called "tubular pinch" effect, the lateral migration of rigid spheres. We have also discussed the transverse motions of liquid drops, and the reversibility of the organization of suspensions in transport. The convective accelerations in the entrance region of a tube can produce relative velocities between fluid medium and various type of particulates if there is a difference in density. The deformable RBC, an "active-type" particle, can provide feedback to the flow from both mass and momentum considerations; the more rigid platelet, a "passive-type" particle, will experience a much smaller relative velocity as compared to the RBC. We may expect that particles of different densities are transported to different equilibrium annular positions before entering the fully developed flow region. The erratic, lateral movement of suspended particulates in steady laminar tube flow can be described by the usual Lagrangian coordinates. PMID- 1298452 TI - Improved diagnosis with digital radiography. AB - In radiodiagnosis, much effort is spent in reducing the radiation dose and simultaneously improving the information obtained with radiographs. Computer technology has the potential to significantly impact radiography in medicine and in dentistry to achieve these goals. Advanced digital imaging techniques will be available for the general practitioner within the next decade. Storage and retrieval of images, contrast enhancement, and noise reduction are some examples of basic image manipulation tools. Subtraction radiography and image reconstruction will improve diagnosis and treatment planning. The clinical knowledge of dentists and radiologists will be incorporated into computer programs to perform more sophisticated tasks in the form of automated image analysis and computer-aided image interpretation. PMID- 1298453 TI - Orthodontic treatment in the mixed dentition for the general dentist. AB - Mixed dentition treatment is an important subject because early treatment could not only correct the occlusion but also may ensure normal development of the teeth. Proper arch form and dental relationships in the mixed dentition lessen the need for additional orthodontic treatment. The objectives in mixed dentition orthodontic therapy are to correct dental arch irregularities, occlusal and jaw relation abnormalities, and to eliminate functional interferences. PMID- 1298454 TI - Growth and development in orthodontics. AB - The recent literature on growth and development of the face and dentition includes important articles about assessment of growth, maturation, growth in the vertical dimension, treatment effects, experimental growth, and craniofacial anomalies. An underlying theme can be detected in these reports--the individuality of the child and his or her response to treatment. Central trends can be determined from growth data, but these generalizations should be applied with caution. When formulating treatment goals and planning mechanics, great variability can exist among growing children. PMID- 1298455 TI - Complications of orthodontic treatment. AB - Orthodontic treatment may in some cases initiate damage to teeth and supporting tissues (decalcification and gingivitis) or root resorption, pulp damage, allergic reactions, or craniomandibular dysfunction. This review updates some interesting findings regarding these problems. PMID- 1298456 TI - Current concepts in education and research in orthodontics. AB - The science of dentistry is quickly advancing toward the 21st century. The constant innovations in dental material development, along with the ever-new concepts that are emerging in basic science and clinical research, are helping dentists to design methods of practice that have a more biologic and preventive substrate and a less restorative aim. As a result, all specialties of dentistry are undergoing constant changes in an effort to conform and manage the need of an educated, modern society. This report highlights some current concepts in orthodontic education and clinical research that are shaping the way that the specialty of orthodontics is taught and practiced. PMID- 1298457 TI - Dentin bonding agents. AB - Dentin bonding is discussed both in terms of the substrate and in terms of newer bonding systems that have recently been marketed. The most popular bonding systems are presented along with several new systems from Germany and Japan. Etching of dentin is discussed in terms of both its advantages and its disadvantages. Bonding systems can be used to repair fractured teeth as well as to restore carious teeth. This area of knowledge is rapidly expanding. Most of the new products are improvements over their predecessors. PMID- 1298458 TI - The need for long-term multicenter treatment assessment of craniofacial developmental disorders including cleft lip and palate. AB - There has been an increase of interest in recent years in comparing treatment outcome in patients with craniofacial anomalies, including cleft lip and palate. When a treatment result is to be evaluated, it is important that it is multifaceted, taking all aspects into account. A comparison between treatment outcome in six centers showed that those with simple procedures and few surgeons involved in the primary operations had as good treatment results as those with more complicated treatment procedures. The center that used presurgical orthopedics with extraoral strapping in its treatment program ranked low as did the center employing primary bone grafting as part of the treatment program when compared with the other centers. PMID- 1298459 TI - The child as a dental patient. AB - The management of children's anxiety continues to be at the focal point of research into the child as a dental patient. This review is concerned first with different psychological concepts of anxiety, including psychoanalytic approaches, infant attachments, and behavioral and cognitive approaches. Incidents contributing to fear of dentistry and strategies used to manage anxiety and behavioral problems are then considered. The next section deals with coping mechanisms children devise to deal with anxiety-provoking situations. Finally, some comments are made on groups of children with special needs. The decline in caries and an increase in the awareness by dentists of the psychological needs of children should enable the next generation to be less fearful and more positive about the benefits of good dental health. PMID- 1298461 TI - Bibliography of the current world literature. Orthodontics. PMID- 1298460 TI - Advances in the treatment of acquired and developmental defects of hard dental tissues. AB - With the decline in dental caries, the dental profession and the general public have become sensitized to the "new" specialty of cosmetic dentistry. As a consequence, research in the field of dental materials for the ideal, most natural restorative materials and techniques has become a primary focus and has had a profound influence on dental education and practice. This brief article will highlight some of these newer concepts. PMID- 1298462 TI - Bibliography of the current world literature. Pedodontics. PMID- 1298463 TI - Diagnosis and treatment planning in orthodontics. AB - Orthodontic diagnosis and treatment planning topics either reflect the new technology available in the health fields or reiterate the older material that reemerges from generation to generation. Issues that are presented still display the dissatisfaction of their examiners in terms of frustration and equivocal results. Well-controlled prospective and retrospective studies require documented long-term evaluations to be clinically useful as an aid in diagnosis or formulation of treatment planning principles. PMID- 1298464 TI - [Relation among syndrome of spleen deficiency and stagnation of liver-qi and electrogastrogram, gastric mucosal pathology and pulse-cardiovascular function in chronic gastric diseases]. AB - In this research, Syndrome of Deficiency of Spleen (DS) and Stagnation of Liver Qi (SLQ) as well as observations of electrogastrogram (EGG), gastric mucosal pathology and pulse cardiovascular examination were investigated in 56 cases of chronic gastric diseases (CGD). The results showed: (1) In SLQ with DS the amplitude of EGG was significantly higher than that of the control group (P < 0.01), it often indicated the active period of pathologic change, but in DS with SLQ, the amplitude of EGG was significantly lower than that of the control group (P < 0.01), it frequently denoted the static period. In case that DS equalled to SLQ, the amplitude of EGG was significantly higher than that of the control group (P < 0.01). It revealed that there were no significant difference between the patient's number of static and active periods (P > 0.05). It is valuable in Syndrome Differentiation of Deficiency and Excess and analysis of Superficiality and Origin in CGD. (2) Cardiovascular function was also affected in Syndrome differentiation of DS and SLQ. DS with SLQ manifested itself as reduction of left ventricle pump and declination for metabolism of microcirculation, they had significant difference as compared with the control group (P < 0.05), while SLQ with DS or equality between DS and SLQ had the normal function of left ventricle pump and metabolism of microcirculation, even though cardiac output were higher than that of control group (P < 0.05). It showed that the traditional Chinese medicine theory of interrelation among Heart and Spleen, Liver had their own hemodynamic bases. PMID- 1298465 TI - [Relation between Helicobacter pylori and pathogenesis of chronic atrophic gastritis and the research of its prevention and treatment]. AB - The total detectable rate of Helicobacter pylori (HP) of 485 patients suffering from gastric diseases was 59.6%. The HP in gastric mucosa of chronic atrophic gastritis (CAG) patients was separated from the cell culture in vitro and transferred successively. The mice were perfused with exciccate alum, and the rabbits with aspirin to injure their gastric mucosa, then HP was perfused. Result showed that the change of experimental animals was identical with that of CAG patients by means of bacteriological and pathological examination. It revealed that HP was in agreement with Robert Koch's three principles about pathogenic bacteria. According to the bacterial infectious hypothesis of CAG, 53 Chinese medicinal herbs and prescriptions were investigated with bacteriostatic test. Panax notogenseng and Magnolia officinalis were discovered to be sensitive, Prunus mume and Corydalis yanhusuo were moderate sensitive, and Coptis chinensis and Rheum palmatum highly sensitive to HP. Decoction of Clearing up the Heat and Relieving the Blood Stasis and No.2 recipe of Huowei were used to treat 70 CAG patients with Stomach Heat Syndrome. The effective rate of gastroscopic examination was 85.7%, that of pathological study was 80%. In comparing with the group of Shanjiu Weitai, there was significant difference between the traditional Chinese medicine treated group and Shanjiu Weitai control group, the former being markedly better. PMID- 1298466 TI - [Combined traditional Chinese and Western medicine in the treatment of intractable ulcer]. AB - The curative effects of combined traditional Chinese and Western medicine in 508 patients of intractable peptic ulcer with gastroscopy confirmation were evaluated. The patients were divided into Chuanjia Weidan group (Group I, 260 patients) and cimetidine group (Group II, 248 patients). Debridement, injection and drug covering of ulcer surfaces were followed by oral Chinese medicine Chuanjia Weidan (50 g daily) or cimetidine (800 mg every night) for 4 weeks. In group I, 95.6% of patients with gastric ulcer were cured, while in group II, 87.2% with the same disease were cured. For the patients with duodenal ulcer in group I and group II, 88.2% and 85.2% were cured respectively (P > 0.05). 70% of the main symptoms were remitted in the first and 97% in the second week in group I, whereas in group II, the remission occurred in 33% and 64.5% respectively (P < 0.05). The clearance rate of Helicobacter pylori for gastric ulcer and duodenal ulcer in group I was 71.2% and 78.3% respectively, but 5.3% and 7.2% in group II (P < 0.01). Eighteen months after the treatment, 13% of the patients with gastric ulcer and 14.2% with duodenal ulcer in group I relapsed, while that of group II was 63% and 71.3% respectively (P < 0.01). The authors concluded that debridement, injection and drug covering of ulcer surface under the endoscopy associated with oral administration of Chinese medicine Chuanjia Weidan is efficacious in treating intractable peptic ulcer. PMID- 1298467 TI - [Effects of various qigong breathing pattern on variability of heart rate]. AB - The effects of four various Qigong breathing pattern on variability of heart rate have been observed by R-R interval spectral analysis in 26 healthy volunteers. The differences in the shape of peaks in spectra were found to be correlated with the Qigong breathing pattern. The amplitude of peak in high-frequency area increased with a reduction of the low-frequency 2/high-frequency (LF2/HF) ratio during the Qigong breathing pattern A, B, and C, indicating the vagal activity increased during above-mentioned three Qigong breathing pattern. However, the amplitude of peak decreased and LF2/HF ratio increased during the Qigong breathing pattern D, it reflected the increase of sympathetic activities. Thus, the results suggested that the Qigong could indirectly regulate the function of viscera after controlling the direct breathing pattern. PMID- 1298468 TI - [Efficacy of danggui funing pill in treating 162 cases of abdominal pain]. AB - Therapeutic effect of Danggui Funing (DGFN) pill in treating 207 patients with abdominal pain were studied with control. Among 207 patients with abdominal pain, 162 of DGFN pill group and 45 of control groups (35 atropine group and 10 placebo group). The effective rate of abdominal pain in the three groups were 93.27%, 97.14% and 0% respectively. There was no significant difference (P > 0.05) between the DGFN pill group and the atropine group, but the difference were statistically significant (P < 0.01) between the above-mentioned two groups and the placebo group. These results revealed that the therapeutic effect of DGFN pill was reliable. There were three pharmacological effects of DGFN pill: The blocking on M, alpha and H1 receptors, the analgesic effect and the antiseptic effect. The DGFN pill was the drug of rapid-efficacy and low toxicity. PMID- 1298469 TI - [Clinical study of rapid bladder filling agent]. AB - The Rapid Bladder Filling Agent (RBFA) was prepared with Polyporus umbellatus, Poria cocos and Furosemidum. The urinary volume and the best filling time of urinary bladder were observed with ultrasonography in 211 cases. The result showed that in experimental group the largest urinary volume in unit time was more than that in control group and shortest filling time was shorter (30.35 +/- 7.9 min) in comparing with control group (145.6 +/- 50.1 min). Clinical observation for 1180 cases proved that the RBFA had the effects of raising the quality of ultrasonographic examination and escalating work efficiency, shortening the waiting time of patients and relieving patients' suffering from excessive filling of urinary bladder. The effective time of the RBFA was fast but the duration was short. The RBFA had no adverse effect. PMID- 1298470 TI - [Blood and urine prostaglandin E2 and prostaglandin F2 alpha in patients with chronic gastritis and peptic ulcer]. AB - The blood and urine prostaglandin E2 (PGE2), Prostaglandin F2 alpha (PGF2 alpha) in 106 cases of chronic gastritis and peptic ulcer were investigated by RIA. Meanwhile, the relationship among PGE2, PGF2 alpha and the Syndromes of TCM were approached. The result showed: In comparing with the normal control, the blood and urine PGE2 of 106 cases were obviously higher (P < 0.01), but PGF2 alpha was not (P > 0.05). The urine PGE2 and PGF2 alpha of moderate gastritis were markedly higher than those of mild gastritis (P < 0.05), but there were no significant difference between blood PGE2, PGF2 alpha of moderate gastritis and those of mild gastritis (P > 0.05). The blood PGE2, PGE2/PGF2 alpha ratio of Dampness-Heat in Spleen-Stomach Syndrome and the blood PGE2/PGF2 alpha ratio of incoordination between Liver and Stomach Syndrome were higher than those of Spleen Stomach Deficiency Syndrome in all the cases (P < 0.05). Compared with the normal control, both the decreased amplitude of blood PGE2/urine PGE2 and increased amplitude of blood PGF2 alpha/urine PGF2 alpha ratio showed as following: Spleen Stomach Deficiency Syndrome > incoordination between Liver and stomach Syndrome > Dampness-Heat in Spleen-Stomach Syndrome. This study suggested: (1) There was a close relation between PGE2 and chronic gastritis and peptic ulcer; (2) There was no correlation between blood PGE2, PGF2 alpha and urine PGE2, PGF2 alpha; (3) PG was possibly a useful objective parameter to the Syndrome Differentiation in TCM. PMID- 1298471 TI - [Effects of buyang huanwu decoction on changes of oxygen free radical and cell ultrastructure in rats with experimental brain edema]. AB - Effects of Buyang Huanwu decoction (BYHWD) on the change of oxygen free radical and cell ultrastructure were observed in rats with acute brain edema induced by pertussis vaccine (PV). The results showed that BYHWD could decrease significantly the contents of brain tissue protein and malondialdehyde, and raise the declining of superoxide dismutase and glutathione peroxidase activities. Also, BYHWD could reduce markedly the transport of pinosome in the left cerebral capillary endothelial cell, and lessen slightly the swelling of cerebral perivascular astrocyte processes and mitochondria in neuron. There was no significant reduction of water content in the left hemisphere on intravenous administration of BYHWD before and after injecting PV; while that in the right hemisphere, it was less remarkable in BYHWD group than that in control (P < 0.05). Hence, it suggests that BYHWD had the evident effects in antagonizing the damage of blood brain barrier and encephalic cell caused by free radical in brain edema. PMID- 1298472 TI - [Experimental and clinical research of dachengqi decoction in treating post traumatic respiratory distress syndrome]. AB - 12 cases of post-traumatic RDS treated with Dachengqi Decoction were reported. RESULTS: 10 patients survived, which showed a bright prospect for the treatment of post-traumatic RDS. In the experimental study, model of RDS was set up in rabbits. The pressure of PaO2 was determined and the morphologic changes of their lung tissues was observed after the rabbits were perfused with Dachengqi Decoction. The results showed that their PaO2 were markedly increased and lung conditions greatly improved, which provided an experimental basis for RDS with Dachengqi Decoction. Among 12 cases; nine were moderate cases and three serious ones. During the course of treatment with Dachengqi Decoction, two patients died, covering only 16.6% of the total number of patients. This fact confirms the efficacy of Dachengqi Decoction in treating the post-traumatic RDS. PMID- 1298473 TI - [Application of infrared thermography for study of acupuncture and meridians]. PMID- 1298474 TI - [Aplastic anemia treated by traditional Chinese medicine combined with Western medicine]. PMID- 1298475 TI - [Evaluation of problems concerning traditional Chinese medicine research on chronic atrophic gastritis]. PMID- 1298476 TI - [Pharmacological action and clinical application of palmatum]. PMID- 1298477 TI - Treatment of patients with oral related behavioural problems--a multidisciplinary approach. PMID- 1298478 TI - Women in the culture of dentistry. PMID- 1298479 TI - Health hazards in the semiconductor industry. A review. AB - The development of semiconductor production has been accompanied by an increased use of toxic production materials and an increased release of potential toxic wastes, which are harmful to health and environment. This paper gives an overview of occupational health hazards resulting from production materials in the microelectronics industry and from waste products originating as gases from plasma etching processes in photolithography during semiconductor production. The paper proposes methods for using experimental toxicology to investigate the occupational risks from complex mixtures of chemicals in the semiconductor industry. PMID- 1298480 TI - An ergonomic system for assessing postural stress in workplaces. AB - A new method has been developed to enable the ergonomic assessment of stress associated with posture at the workplace. It enables evaluations of the load resulting from working postures at workplaces where standing and walking postures dominate. The method also offers the possibility of estimating the preexisting load already at the stage of workplace designing. This may prove useful in evaluating both the global load and giving the designer an idea about the effect of individual design decisions on changes of the postural load. The method has been used to compare the postural stress at several workplaces in the textile industry and it seems to perform satisfactorily. PMID- 1298481 TI - The influence of occupational and non-occupational factors on chronic fatigue in women. AB - The aim of the present study was to assess the significance of different types of loads to which working women are subjected in relation to reported chronic fatigue. The investigation involved 255 women workers from two different occupational groups. The first group was employed at knitting and the second at assembly lines. Their level of chronic fatigue was assessed. We also analysed the influence of 30 variables on fatigue level. These variables concerned: a) physical and psychological workload, b) organizational (social) climate of work, and c) demographic and family factors. It was found that the most important factor influencing chronic fatigue was "experiencing emotional tension" resulting from family problems. Other factors, having substantial significance for the development of increased fatigue level were also associated with emotional tension and resulted from the social climate in the workplace. PMID- 1298482 TI - Occupational and environmental exposure to nickel in Poland. AB - Exposure to nickel was evaluated on the base of nickel in urine concentration (Ni U) in 649 persons both adults and pre-school and school children; 241 persons were occupationally exposed in steel-mill and rolling-mill. Environmentally exposed groups consisted of inhabitants of industrial and rural towns. The occupationally exposed groups showed Ni-U mean concentrations amounted to 25.7, 18.1, 15.9, and 15.7 micrograms/m3. In environmentally exposed groups of adults, Ni-U concentrations were almost equal to those in persons inhabiting industrial and rural areas-7.8 and 7.7.micrograms/dm3, respectively. Ni-U concentrations in children groups were more differentiated 8.5 and 9.2 micrograms/dm3 in rural area and 9.9 and 10.6 micrograms/dm3 in industrial area. The recommended mean group allowable Ni-U concentrations for occupational exposure amounts to 12 micrograms/dm3 and for environmental exposure 2.7 micrograms/dm3. In view of the above mentioned Ni-U allowable values it is evident that there exist significant occupational exposure and elevated environmental exposure in the defined percent of the investigated population. PMID- 1298483 TI - The study of exposure to cadmium in the general population. II. Morbidity studies. AB - An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium polluted areas of CSFR (Pribram and Frydek-Mistek) is associated with changes in biological indicators of renal dysfunction in non occupationally exposed population groups. Polluted areas were chosen on the basis of existing sources of Cd emission. The city of Prague was selected as a control area. Environmental monitoring (Cd in air, dust fall and soil) did not confirm significant contamination of selected areas. It was found that Cd levels in urine (Cd-U) of inhabitants living in areas chosen as Cd-contaminated were significantly higher than in the control area. Differences in concentrations of Cd in blood (Cd-B) levels between individual areas were not significant. No significant differences between the study populations were noted in the urinary excretion of low molecular weight proteins (beta 2-microglobulin, retinol binding protein) and albuminuria. However, total proteinuria and aminoaciduria in persons living in Pribram area was significantly higher. This area suffers from combined contamination by cadmium and lead. In smokers of both sexes the Cd-B levels were significantly higher in all areas, no significant differences were found in Cd-U levels. However, it was found that in smokers there is higher percentage of persons excreting more than 0.9 micrograms Cd.g-1 creatinine in urine. Consumption of home-grown vegetable and fruit in Cd-polluted areas led to significantly higher levels of Cd-B and Cd-U and total proteinuria. The results of the study show that smoking and food seem to be the most important sources of Cd intake in non-occupationally exposed populations. In spite of the fact that environmental monitoring does not reveal a significant contamination of selected areas by Cd, Cd-U levels confirmed that population living in these areas is really exposed to Cd. PMID- 1298484 TI - Correlation between polycyclic aromatic hydrocarbons concentration and airborne particle mutagenicity in the rubber factory. AB - The study was undertaken to evaluate the correlation between benzo[a]pyrene and coal tar pitch volatiles concentrations and mutagenic activity of airborne particles sampled at different workplaces of the factory producing various types of tires. The solid phase of aerosols was collected on Whatman glass-fibers filters using Staplex pumps. Coal tar pitch volatiles (CTPVs) were extracted from sample filters using ultrasonic-benzene extraction and determined by the gravimetric method. Benzo[a]pyrene (BaP) analysis was performed using high performance liquid chromatography with a spectrofluorimetric detector. The mutagenic substances were extracted from collected material with acetone. The mutagenic properties were estimated with the Ames' test using S. typhimurium strain TA98 without and with S9 fraction. At nearly all workplaces the concentrations of BaP and CTPVs were within the range of 4-61 ng/m3 and 0.11-1.26 mg/m3, respectively. Only at weighing were they much higher and amounted to 172 2261 ng/m3 for BaP and 3.05-4.07 mg/m3 for CTPVs. The highest exposure to mutagenic airborne particulate matter was found at weighing (1500 rev/m3), the mixers loading level (> 500 rev/m3) and the carbon black station (> 150 rev/m3). The air mutagenic activity at other workplaces, especially at the extruder mill of the mixer (> 90 rev/m3), the two-roll mill of mixers (> 70 rev/m3), mixer I loading (> 70 rev/m3), calendering (> 70 rev/m3) and fender vulcanizing (> 80 rev/m3) was even much more higher than that found in the urban indoor and outdoor air (2-9 rev/m3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298485 TI - Urine mutagenicity in workers directly employed in coke production. AB - Mutagenicity and toxicity of urine samples of 30 coke oven workers (group I) and 26 individuals composing a control group (group II) was estimated using Ames test with Salmonella typhimurium strains TA 98 and TA 100. Urine mutagenicity and toxicity, tested with strain TA 98 and metabolic activation, was significantly higher in group I than in group II. Using the strain TA 100, urine samples of coke oven workers showed only direct toxicity. Mutagenic and toxic activity was observed mostly in workers exposed to the highest BaP concentrations. No correlation was found between obtained results and tobacco smoking. Increased urinary mutagenic activity in group I resulted from exposure to very high BaP concentrations. It is concluded that urine samples of exposed coke oven workers should be periodically tested for mutagenic activity. Workers with mutagenic urine ought to be shifted to work posts with lower exposure to mutagens. PMID- 1298486 TI - Environmental Health Perspectives, the journal of the National Institute of Environmental Health Sciences. PMID- 1298487 TI - Duration of anesthesia using the periodontal ligament injection: a comparison of bupivacaine to lidocaine. AB - The purpose of this study was to compare the duration of pulpal anesthesia obtained with 0.5% bupivacaine HCl with 1:200,000 epinephrine to 2% lidocaine HCl with 1:100,000 epinephrine, using the periodontal ligament (PDL) injection. Twenty-four subjects received bilateral PDL injections using mandibular premolar teeth and a double-blind research design. Anesthesia was defined as no response to maximum output of an electric pulp tester. An overall success rate of 35.4% was achieved. Duration of anesthesia obtained with bupivacaine HCl ranged from 4 minutes 59 seconds to 16 minutes 37 seconds with a mean duration of 10 minutes 24 seconds. Excluding one instance in which the duration was three orders of magnitude beyond the norm, duration of anesthesia obtained with lidocaine HCl ranged from 1 minute 43 seconds to 16 minutes 16 seconds with a mean duration of 7 minutes 10 seconds. Postoperatively, all experimental teeth tested vital with no clinically apparent pulpal or periodontal damage. Some postoperative discomfort was experienced at 16.6% of the injection sites. PMID- 1298488 TI - A case of coronary artery spasm during oral surgery under general anesthesia. AB - A case of coronary artery spasm during oral surgery under general anesthesia is reported. The patient, aged 44 years, 160 cm in height, and 55 kg in weight, was scheduled for radical surgery for right maxillary sinusitis and was healthy except for the disease requiring surgery. Just before the start of the surgery, severe and persistent hypotension with tachycardia after local injection of 3% propitocaine with 0.03 IU/mL felypressin (Citanest-Octapressin) was followed by sudden ST elevations in the ECG. Immediate continuous intravenous injection of nitroglycerin was thought to be effective. The patient recovered without any sequelae. PMID- 1298489 TI - Protocol for studying depth of anesthesia using the spectral edge frequency. AB - The preliminary results of a multicenter study designed to determine the utility of the processed EEG in combination with heart rate and blood pressure for estimating anesthetic depth are reported. The study is planned to include 1,000 ASA I, II, and III patients undergoing surgery with at least a 60-minute duration of anesthesia. The preliminary results indicate that the use of EEG and clinical signs may provide better control of anesthetic depth. The study design provides ideal conditions for determining whether spectral edge frequency is a useful criterion for management of routine general anesthesia in a typical clinical environment. PMID- 1298490 TI - Vertex potentials evoked by nociceptive laser stimulation of oral mucosa: a comparison of four stimulation paradigms. AB - A new method for quantitative assessment of oral mucosal nociception and analgesia has been introduced using vertex potentials elicited by nociceptive argon laser stimuli. Four different stimulation paradigms (long, random, warning, and self-triggered) were compared to determine which technique elicited the most reproducible vertex potentials. A warning stimulation paradigm applied on the tongue and hand elicited vertical potentials with smaller amplitudes, lowest intraindividual coefficient of variation (16.5% and 7.9%, respectively), and highest reproducibility. The latency of the major negative peak was not affected significantly by different stimulation paradigms. The high reproducibility of vertical potentials elicited by the warning stimulation may be ascribed to a standardized psychological state of the subjects. PMID- 1298491 TI - Tenoxicam for pain relief following third molar surgery. AB - Tenoxicam is a long-acting nonsteroidal anti-inflammatory agent that appears to have the ability to control pain of musculoskeletal origin. A double-blind randomized crossover study was designed to determine the efficacy of tenoxicam for pain relief following third molar surgery by comparing it with paracetamol. Immediately before surgery, 30 Chinese patients with bilateral symmetrically impacted mandibular third molars were given 40 mg of tenoxicam for surgery on one side and 1,000 mg of paracetamol for surgery on the other. Both paracetamol and tenoxicam were efficient as pain relievers after third molar surgery. Tenoxicam had comparable efficacy to paracetamol, but did not provide any advantage in terms of duration of action. The discrepancy between the clinical observation and pharmacokinetic prediction may be related to the strong serum binding property of tenoxicam. PMID- 1298492 TI - Analysis of abnormal electrocardiogram observed during surgery: Part 1. Lead placement methods and artifacts. AB - The fundamentals of electrocardiographic diagnosis and the types of abnormal ECGs frequently found during surgery are described in this two-part article. Part 1 discusses lead placement and artifact recognition. Part 2 will describe arrhythmia and atrial fibrillation and flutter. Clinical situations of each are analyzed. PMID- 1298493 TI - Education in dental anesthesia in the United Kingdom. AB - This paper describes the present system of education and training for doctors and dentists providing general anesthesia or conscious sedation for dental treatment in the United Kingdom. The changing pattern of practice in these areas is outlined in the context of a changing medicolegal climate, together with the possibilities for future development. PMID- 1298494 TI - The Baldrige Award: an approach for self-evaluation. PMID- 1298495 TI - The customer's voice in health care. PMID- 1298496 TI - Six tips for effective presentations. PMID- 1298498 TI - Databases. PMID- 1298497 TI - Skin integrity of the CV surgical patient. PMID- 1298499 TI - Spark erosion implant-supported overdentures: clinical and laboratory techniques. AB - Overdentures can be utilized effectively in treatment plans involving implants. Usually soft tissue support is necessary, which requires a conventional denture base. Implant-supported overdentures do not require conventional denture base extension unless necessitated by functional or esthetic considerations. With fixed-detachable hybrid dentures, flanges can often interfere with home care procedures. Spark erosion overdentures meet the requirements for esthetics, phonetics, retention, and support and also allow accessibility for proper patient oral hygiene. This article reviews the advantages and disadvantages of the spark erosion overdenture and provides guidelines for the fabrication of this type of prosthesis. PMID- 1298500 TI - Hydroxyapatite coatings in implant dentistry. AB - Hydroxyapatite coatings have shown promise due to the enhanced integration of osseous tissues to coated implant surfaces. When compared with healing around commercially pure or titanium alloy implant surfaces, hydroxyapatite-coated implants appear to be superior in sites which are compromised in either quantity or quality of bone. In spite of these encouraging findings, the long-term stability of the hydroxyapatite/bone interface has been challenged. Microbiologically, the hydroxyapatite-coated implant surface may be at an increased risk to bacterial plaque. However, after 8 years of clinical utilization, the hydroxyapatite-coated implant surface has not been shown to be predisposed to increased long-term failure. Available research as it pertains to this controversial area of implant dentistry is reviewed. PMID- 1298501 TI - Use of implants to restore dentition in a partially resected mandible: clinical report. PMID- 1298502 TI - Externally hexed implants, abutments, and transfer devices: a comprehensive overview. AB - An extensive overview of dental implant abutments for coronally hexed implants is presented. Abutment technology, indications, and contraindications for abutments are discussed. Various implant designs from 16 commercial manufacturers with over 64 abutment variations and transfer concepts are illustrated. PMID- 1298503 TI - Evaluation of the interprobe electronic periodontal probe. AB - The Interprobe is designed to provide measurements of pocket depths and attachment loss. Investigators involved in a clinical study on dental implants being conducted by the Dental Implant Clinical Research Group participated in an in vitro evaluation of the variability of repeated measurements made with the Interprobe. Measurements were made on holes drilled to predetermined depths in metal blocks. Three readings by investigators for each of nine test holes were in agreement 75.2 percent of the time. At least two of three readings were in agreement in 98.1 percent of the attempts. Either two of three or three of three readings were within 0.5 mm of the actual depth of the holes over 99 percent of the time. No correlation was noted for accuracy of measurements with hole depth or present clinical duties of the investigators. Although slight initial improvement in measurement accuracy was observed, it was not statistically significant in time over the three measurement sequence. PMID- 1298504 TI - Issues in bone mechanics related to oral implants. AB - The development and maintenance of the dental implant-to-tissue interface is clearly of paramount importance in the determination of clinical success. Yet, the precise mechanism with which bone responds to mechanical load remains unknown. A review of current thought on the performance of cortical and cancellous bone as structural foundations for dental implants is provided, with particular emphasis on the influence of its three-dimensional architecture at the macroscopic level. The mechanical response of bone is reported to depend upon the direction, magnitude, rate, and duration of loading. Quantitative relationships have been established to correlate cancellous bone strength and stiffness to its apparent density. Such data provide useful insights into the modeling/remodeling response of bone tissue, which is arguably the ultimate predictor of implant longevity. PMID- 1298505 TI - The transmandibular implant: implant reconstruction and rehabilitation for the atrophic mandible. AB - The transmandibular implant is specifically designed for the reconstruction and rehabilitation of the severely atrophic mandible utilizing an extraoral approach. The unique design and surgical protocol of the transmandibular system have proven to be predictable and successful. The indications, implant design and materials, surgical technique, advantages, and disadvantages of the transmandibular system are presented in this article. PMID- 1298506 TI - The effect of educational approach on knowledge, attitudes and dietary habits of adults with borderline cholesterol levels. PMID- 1298507 TI - The lived experience of adult women survivors of childhood incest: a Heideggerian hermeneutical analysis. PMID- 1298508 TI - Health-promoting behaviors of African American elderly. PMID- 1298509 TI - Scientists gear up to fight TB. PMID- 1298510 TI - Educators brace for the next nursing shortage--too few faculty. PMID- 1298511 TI - Education and service partnerships for differentiated practice. PMID- 1298512 TI - Abilities and expectations: matching those of nurses with their health care organizations. PMID- 1298513 TI - Case management provides flexibility, opportunity for nurses as managers. PMID- 1298514 TI - Differentiated practice: where are we in the research today? PMID- 1298515 TI - Differentiating nursing practice into the twenty-first century: Kansas City: Missouri: American Academy of Nursing. PMID- 1298516 TI - Implications of the quality improvement philosophy in service for differentiated nursing practice: what will be the effect of the quality movement in health care on efforts to differentiate nursing practice? PMID- 1298517 TI - Try to capture the meaning of an acronym--PDQ!! PMID- 1298519 TI - Clinical religious research, how to enhance risk of disease: don't go to church. PMID- 1298518 TI - Validating differentiated practice in new ADN and BSN graduates: implications for education and practice. PMID- 1298520 TI - Diastole. The importance of rest. PMID- 1298521 TI - Back to the basics in medicine & dentistry: the calling, the profession. PMID- 1298522 TI - [Current trends in cosmetic surgery in China]. PMID- 1298523 TI - [Double-circle-incision for reduction mammaplasty]. AB - The authors have used the double-circle incision for reduction mammoplasty on 55 breasts in 28 patients. The main features of the technique are: 1. Complicated and rigid preoperative markings are substituted by a simple and flexible double circle incision; 2. Proper dissection between the skin and glandular tissue instead of non-dissection; 3. A conic stump of residual glandular tissue is formed instead of a cylindrical stump; 4. Glandular remodelling is substituted by skin "brassiere" retailoring; 5. The nipple-areola site is determined at the end instead of being the first step of the operation. The clinical results revealed that this new method is suitable for medium or large hypertrophy, especially for young women with good, thick and elastic skin, but it is not suitable for macromastia or severe breast ptosis. PMID- 1298524 TI - [A preliminary study of the fibrous capsules around silicone mammary implants in Chinese women]. AB - Specimens obtained from 17 fibrous capsules around the silicone implants were examined with naked eye, and light and electron microscopy. Immunohistochemical staining with various monoclone antibodies was used. It was demonstrated that the main infiltrating cells in the fibrous capsules were mononuclear cells, denoting a rejection reaction. Fibrous tissue was formed to separate the prosthesis from the normal tissue. PMID- 1298525 TI - [The pH value of granulating wound and skin graft in burn patients]. AB - The relationship between pH of granulation of burn wound and take rate of skin graft was presented. The bacteria in the granulation tissue were also quantified. The results showed: (1) The optimal pH of granulation wound for the take of skin graft is 7.2-7.5; (2) pH of granulation of burn wound is related to quantity and species of bacteria in the granulation tissue. The wound pH is 6.7 or lower when the number of Escherichia coli or Staphylococcus aureus is over 10(7)/gm of granulation tissue. The wound pH is 8.0 when the number of Pseudomonas aeruginosa is 10(8)/gm of granulation tissue. Because the measurement of wound pH is rapid, simple and noninvasive, it might be useful in predicting the take rate of skin graft. PMID- 1298526 TI - [Clinical observation of face peeling treatment for ephelides and phenol excretion in urine]. AB - Since 1986, 710 patients with freckles were hospitalized, and the effects of face peeling were studied. Before treatment, blood and urine routines and hepatic and renal function tests were performed in every patient. Comparisons have been made between the hepatic and renal functions before and after treatment in 100 patients. ECG was performed in all the patients before treatment, and 20 of them have been monitored continuously with ECG after treatment. Comparison of 24h urinary phenol excretion before and after treatment were made in 27 patients. In 5 patients it was showed that the amount of urine phenol declined rapidly with the time. The treatment was effective in 100% of the patients. The cure rate was 84.2%. We concluded that the treatment is an effective and safe method for ephelides in healthy persons. PMID- 1298527 TI - [Calcium alginate film, its preparation and application on donor area of split thickness skin graft]. PMID- 1298528 TI - [Changes in expression of interleukin-2 and interleukin-2 receptor in lymphocytes in patients with burns]. AB - IL-2 mainly combines with the IL-2R on the membrane of the lymphocyte, both to promote activation and proliferation. The expression of IL-2 and IL-2R on the lymphocyte was found to be significantly depressed after burn injury. IL-2 was decreased by 40%-60%, and the expression of IL-2R was decreased by 25%-55%, especially on the 7th day after burn. The results demonstrated that burn injury not only influenced the production of IL-2 from T helper cell, but also depressed the expression of IL-2R. PMID- 1298529 TI - [Elongation of short penile shaft]. PMID- 1298530 TI - [Plastic surgery of pseudo-hermaphroditism]. AB - The paper introduced the method of plastic surgery for pseudo-hermaphroditism in 8 patients. Which sex would the patient be finally in should only be determined by the desire of the patient and the patient's family. The results were satisfactory. The technique and problems involved in the operative procedure are discussed. PMID- 1298531 TI - [Implantation of sensory nerve into flap: an experimental study and clinical application]. AB - Experimental implantation of sensory nerve into flaps was done, with the purpose of restoration of sensation of the flaps. A scanty amount of nerve endings were found in the vicinity of the implantation after 2 months, obvious regeneration was observed after 3 months, and never endings similar to normal after 4 months. Sensory nerve was implanted into flaps in the hands and feet of 25 patients. 1-2 year follow-up showed that pain, temperature and tactile sensations recovered to normal, and two-point discrimination was 11-22 mm in the hands and 35-40 mm in the feet. In 3 patients, the implanted nerves were blocked with procaine, and anesthesia of the flaps ensued, thus it was proved that the flaps were innervated by the implanted sensory nerves. PMID- 1298532 TI - [Changes in plasma immunologic reactive beta-endorphin and their effect on lymphocyte response to phytohemagglutinin after thermal injury]. AB - The study of immunosuppression after thermal injury has aroused great interest. The present study is an investigation of changes of plasma ir-beta EP in patients and their effect on lymphocyte responses to PHA following thermal injury, in order to establish a relationship between the immune and neuroendocrine system. Plasma ir-beta EP in eighteen burn patients was determined using the radioimmunoassay. At the same time, autoplasma and the autoplasma treated with anti-beta EP serum had been both tested for their effect on lymphocyte responses to PHA. The levels of plasma ir-beta EP were found to be elevated significantly in every phases during the first three days postburn (P < 0.0005-P < 0.001), and then declined to the normal level on the fourth or fifth day postburn. The lymphocytes cultured with autoplasma showed their inhibited responses to PHA during the first three days postburn and returned to normal on the fourth or fifth day postburn, while the autoplasma treated with anti-beta EP serum had an effect to improve the lymphocyte responses to PHA. The findings suggest that burn stress is a strong stimulation which may elevate plasma ir-beta EP and which in turn decrease the lymphocyte response to PHA. We assume that increased plasma ir beta EP may be one of the main causes of immunosuppression after thermal injury. PMID- 1298533 TI - [Surgical treatment of fibrous osteodystrophy of cranio-orbital region]. PMID- 1298534 TI - [Profuse hemorrhage from the axillary artery in electric burn: prevention and treatment]. AB - A total of 53 cases of electric burns were admitted to our unit during the 1977 1985 period. In 19 cases an upper limb was involved, accounting 35.8 percent of the total. In 15 cases disarticulation of the shoulder was done, and in 3 of them a profuse hemorrhage from the axillary artery occurred as a result of infection of the amputation stumps. The second segment of the axillary artery was ligated during the amputations in the other 4 cases, no hemorrhage occurred in them. PMID- 1298535 TI - [Anatomical study of the vascular structure of the breast, emphasizing the vessels from the deep surface]. PMID- 1298536 TI - [Experimental study of the survival length of random flap influenced by rapid tissue expansion]. PMID- 1298537 TI - [Effects of triamcinolone acetonide film and ointment on collagen formation]. PMID- 1298538 TI - [Experimental study on the reconstruction of vascular links between a pedicle skin flap with preserved subcutaneous vascular network and its implanting bed]. AB - A comparative study of skin flap with a preserved subcutaneous vascular network and conventional skin flap was undertaken in rats with determination of skin temperature, laser Doppler, ink perfusion, microangiography and transparent specimen technics. It was found that all the skin flaps with a preserved subcutaneous vascular network survived after transplantation. Three hours postoperation, the flap microcirculation was poorest (LDF, 28% of the preoperative value). Six hours postoperation, it began to augment, and microvessels containing ink could be seen under microscope at 24 hours, as compared to 3 days postoperation in the controls. On the fifth day, LDF returned to the preoperative level, and the diameter and density of reformed microvessels were similar to the vessels of the adjacent skin. This phenomenon only occurred on the 7th day in the controls. After division of the pedicle on the fifth day, all the flaps survived, while the controls showed partial necrosis. The results indicate that skin flaps with a preserved subcutaneous vascular network can survive on the blood flow of pedicle in the early stage, at 24 hours postoperation flap microvessels begin to reform, and on the fifth day flaps can survive on the reformed microcirculation in spite of the severance of the pedicle. PMID- 1298539 TI - [Prevention of reperfusion injury of an ischemic flap: an experimental study]. AB - Oxygen-derived free radicals are important mediators of tissue injury in experimental island skin flaps that have been subjected to prolonged ischemia (vascular occlusion) followed by reperfusion. In this study, the role of oxygen free radical scavenger, SOD, and a herb, salvia miltiorrhiza, in the protection of cellular damages during total ischemia and reperfusion was study in the epigastric island skin flaps in experimental rats with electron microscopy and the assessment of survival of the flaps. Control flaps subjected to 10 hours of total vascular occlusion showed a high incidence of necrosis when followed for 7 days following release of the vascular occlusion. Treatment with superoxide dismutase and salvia miltiorrhiza prior to the onset of reperfusion significantly enhanced island flap survival to 72.5% (P < 0.001) and to 64.2% (P < 0.05), respectively. The conclusions are: 1. Reperfusion for 10 hours following ischemia for 8 hours in the epigastric island flaps of the rats greatly exaggerated the original injury. 2. SOD and salvia miltiorrhiza may protect the flaps from such injury considerably and enhanced flap survival. PMID- 1298541 TI - [Quantitative assay of p-nitrophenol-N-acetyl-beta-D-glucosaminide in human keratinocyte culture]. AB - Attachment and growth of human epidermal keratinocyte culture can be assayed by counting cells or measuring incorporation of radioactive nucleotides (3H-TdR) during cell proliferation. In this study a rapid colorimetric assay for human epidermal keratinocyte growth and viability has been developed based on the colour reaction of NAG (p-nitrophenol-N-acetyl-beta-D-glucosaminide). The results can be read on a scanning multiwell spectrophotometer and show a high degree of precision. The data of experiments show that the absorbance (OD) is directly proportional to the number of cells. 10(3)-10(6) cells per well (1.5 cm2) can be assayed by controlling the time of colour reaction. This method was used to measure keratinocyte proliferation in different culture systems of different culture conditions, growth factor and keratinocyte growth-promoting activity stimulations. The results were supported by counting cells, measuring of 3H-TdR incorporation, or analysing the area of keratinocyte confluents stained with Rhodanile blue. The main advantages of the colorimetric assay are its rapidity and precision, the avoidance of any radioisotope, and it is capable of handling large numbers of culture. PMID- 1298540 TI - [In vitro study of inhibitory effect of vitamin A group drugs on the growth of human fibrocytes]. PMID- 1298542 TI - [Glucocorticoid receptor (GCR) in canine peripheral lymphocyte during early postburn period]. AB - In this report, using the radio-ligand binding assay with [3H]-dexamethasone (Dex) as the ligand, we studied the changes in glucocorticoid receptor (GCR) in canine peripheral lymphocyte under unstressed condition and during the early postburn period (within 48 hours after burn). The results showed that the apparent binding capacity (Ro) and the apparent dissociation constant (Kd) of GCR were 8468 +/- 993 sites per cell and 10.2 +/- 0.6 nM (n = 6), respectively, under unstressed condition. The number of [3H]-Dex specific binding sites measured by the single saturated analysis (Rs) from 16 healthy mongrel dogs under unstressed condition was 4531 +/- 396 sites per cell. The Rs was decreased sharply at the second post-burn hour, reaching the lowest level of 2501 +/- 460 sites per cell. But it recovered to 78.9% of the level measured in unstressed condition. There was significant negative relationship between the plasma cortisol concentration and GCR levels of lymphocyte. The results suggest that the changes in GCR in postburn period may be related to the down-regulation of GCR by Gc; that GCR may be of very important significance in the pathophysiologic changes after burn injury. PMID- 1298543 TI - [Biological characteristics of fibronectin and its role in wound healing]. PMID- 1298544 TI - [Modification of the sympatho-vagal interaction in mitral valve prolapse syndrome. Evaluation of heart rate variability by spectrum analysis]. AB - To determine whether clinical manifestations in patients with mitral valve prolapse (MVP) are associated with altered sympatho-vagal tone, 46 patients (mean age 27 +/- 6, range 20-45 years; 18 males and 28 females) were studied by power spectrum analysis of RR variability. Patients were divided in 2 groups, according to echocardiographic criteria: Group A: 11 patients with classical MVP; Group B: 35 patients with non classical MVP. These patients were compared with 30 healthy subjects (Group C) well matched for age, body surface area and heart rate. Our findings indicate that at rest there is a significant difference in the high frequency component between Group A and Group C. Similarly, during the increase in sympathetic activity induced by 70 degrees head-up tilt all groups showed an increase in the low-frequency component, that was more evident in Group A. The data generated from our laboratory suggest that mitral regurgitation (Group A) is a probable cause of vagal tone increase and that there is an adaptive long-term mechanism towards sympathetic conditions. In addition, probably the normalization, demonstrable by the effect of sympathetic activity in tilt, can mask a dysfunction that may be differently evoked. PMID- 1298545 TI - [Evaluation of the therapeutic efficacy of pravastatin in monothereapy and in association with gemfibrozil in hypercholesterolemia associated with moderate hyperglyceridemia]. AB - Pravastatin is a new drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the key enzyme in cholesterol synthesis. It prevents mevalonate synthesis, thus reducing cholesterol. Pravastatin also stimulates the expression of LDL receptors, leading to an activation of this specific pathway of LDL catabolism. Gemfibrozil is a fibrate drug. Although the mechanism of hypolipidemic action of fibrates is not conclusively elucidated, it seems to involve reduction of LDL cholesterol secondary to decreased VLDL production and increased VLDL catabolism. Therefore, it might be hypothesized that combination therapy with both agents could afford greater reduction of cholesterol levels as compared to pravastatin alone. This study compared the efficacy and safety of pravastatin in monotherapy or in combination with gemfibrozil in the treatment of primary hypercholesterolemia with moderate hypertriglyceridemia. Thirty-eight subjects (aged 57 +/- 15 years, 25 M and 13 F) with baseline cholesterol levels > 220 mg/dl, were included in the study. Serum triglyceride levels were greater than 170 mg/dl and lower than 250 mg/dl. All patients initially followed 4 weeks of hypolipidemic diet. The patients were there assigned to receive either 20 mg once a day of pravastatin alone (n 13) or 20 mg of pravastatin in association with 600 mg of gemfibrozil daily (n 11). Fourteen additional patient, treated with diet only, served as a control group. The treatment plan provided 18 months of active treatment with clinical and laboratory controls every month. Both groups of treated patients showed a reduction of total and LDL-cholesterol levels. The HDL-cholesterol levels increased significantly both with pravastatin and with gemfibrozil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298546 TI - [Estrogens and ischemic cardiopathy. Problems of clinical interest?]. PMID- 1298547 TI - [Slow and fast AV nodal pathways in tachycardia complicating Wolff-Parkinson White syndrome: report of a case]. AB - Electrophysiologic studies in a patient with intermittent ventricular pre excitation revealed several types of paroxysmal narrow-QRS tachycardia (PSVT). One type of PSVT was characterized by normal retrograde atrial sequences with P waves occurring simultaneously with QRS. This type of PSVT reflected AV nodal reentry with anterograde slow pathway and retrograde fast pathway conduction. A second PSVT reflected alternation of anterograde fast and slow AV nodal pathway conduction and retrograde anomalous pathway conduction. A third PSVT reflected anterograde slow AV nodal pathway and retrograde anomalous pathway conduction. Moreover, discontinuous AV nodal conduction curves (A1A2/H1H2), characteristic of dual AV nodal pathway conduction, were obtained with programmed atrial extra stimulation. These observations suggest that dual AV nodal pathway conduction can coexist with abnormal bypass tract and can be the cause of PSVT in patients with Wolff-Parkinson-White syndrome. PMID- 1298548 TI - [The role of mitral regurgitation in the neurovegetative regulation of mitral valve prolapse]. AB - To define the role of mitral regurgitation (MR) on sympatho-vagal balance in mitral valve prolapse (MVP) patients, we analyzed 41 ambulatory MVP symptomatic patients. Twenty-seven patients (4 males, 23 females, aged 34 +/- 3 years) had significative MR assessed color Doppler, while 14 patients (5 males, 9 females, aged 29 +/- 3 years) had no MR; 36 age- and sex-matched subjects were studied as controls (C). Spectral analysis of heart rate variability (HRV) was performed at rest and during sympathetic activation (tilt). In the whole group of MVP patients spectral components did not differ significantly from C at rest and during tilt. When patients were subdivided in relation to the presence (+) or absence (-) of MR, HRV revealed in MR+ patients at rest an increased high frequency (HF) and a diminished low frequency (LF) component (47 +/- 5 and 41 +/- 5 normalized units, nu) with respect to C (34 +/- 3 and 54 +/- 3 nu, p < 0.05, respectively). Viceversa during tilt, in MR+ patients it was possible to observe a LF increase greater than in C (delta LF: 36 +/- 4 versus 25 +/- 3 nu, p < 0.05). As HF component is currently interpreted as a marker of vagal modulation of HRV, our results suggest an increased vagal tone associated with MR possibly due to stimulation of atrial vagal receptors; moreover, an increased sympathetic responsiveness to tilt seems to characterize MR+ patients. PMID- 1298549 TI - [Analysis of regional kinetics of the left ventricle by integration of morphologic data]. AB - Regional left ventricular (LV) curvature analysis is a useful tool to assess the pathomorphological changes in LV shape which occur in different heart diseases. As LV shape changes follow regular trajectories, we used the curvature extrema and the normalized curvature variations as the features for identifying the movement of the borders during the cardiac cycle (curvature-motion method: CM). The regional curvature was calculated using a windowed Fourier series approximation of contours, in which the number of harmonics and filter-window were locally chosen in order to minimize the reconstruction errors and to maximize the smoothness of the curve. Analysis programs were tested on a series of ventricle-shaped contours, software generated. Left ventricular diastolic and systolic outlines obtained from RAO 30 degrees LV angiography in 24 patients with aortic insufficiency and in 16 subjects without heart disease were analyzed. Left ventricular curvature and regional wall motion were calculated in each subject. In respect to normal subjects, LV shape in aortic regurgitation definitely appears asymmetric because of the elongation of the anterior hemiperimeter and the prevailing expansion of the apical and anterolateral regions. These alterations in cavity geometry correlate to the decrease in pump function. According to these results wall motion analysis using the CM showed a greater extension of LV asynergy, while usual methods as the centerline or the radial one indicate a greater damage of the apical regions. Thus, the CM method seems to be a promising tool for wall motion analysis. PMID- 1298550 TI - Evaluation of regression of left ventricular hypertrophy in hypertensive patients treated with captopril as assessed by magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) was used to assess left ventricular mass (LVM) in 20 mild to moderate essential hypertensive patients with left ventricular hypertrophy (LVH) (LVM > 120 g/m2), treated with captopril alone or combined with hydrochlorothiazide. MRI examination was performed at the beginning (T0) and after 3 months (T3) of active treatment, by using a Philips Gyroscan S15 superconducting system, operating at 1.5 Tesla. We used a multislice-multiphase spin-echo sequence on the short-axis and transverse plane (TE = 30 ms; TR = 80 90% RR). End-diastolic thickness of interventricular septum (IVST) and lateral wall (LWT) were measured. LVM was calculated according to Simpson's rule. The results were: IVST 12.2 mm +/- 0.7 vs 10.9 mm +/- 0.5 (p < 0.001); LWT 11.5 mm +/ 0.9 vs 10.5 mm +/- 0.9 (p < 0.001); LVM 160 (g/m2) +/- 5.5 vs 138.4 g/m2 +/- 6 (p < 0.001), at T0 and T3, respectively. Our study demonstrates a significant regression of LVH in hypertensive patients after 3 months of treatment with captopril and a high accuracy of MRI as a noninvasive technique of measuring the LVM reduction. PMID- 1298551 TI - [Regional coronary blood flow in patients with acute myocardial infarct treated by systemic fibrinolysis]. AB - Thrombolysis has been reported to restore coronary blood flow in patients with acute myocardial infarction (AMI). However, the relationship between fibrinolytic treatment and evidence of myocardial reperfusion has not been adequately assessed. Accordingly, we measured great cardiac vein blood flow (GCVF:thermodilution) in 12 patients (Group 1) presenting with AMI (chest pain < 4 hours and ST elevation in the anterior leads) before and following i.v. urokinase (UK:2 million U/90 min). Ten patients receiving conventional treatment served as controls (Group 2). UK induced a significant increase of GCVF (from 101 +/- 24 to 164 +/- 42 ml/min, p < 0.001). Maximal increase occurred after 50 +/- 54 min from drug infusion. Conversely, changes in GCVF were not significant in Group 2 (from 103 +/- 35 to 106 +/- 31 ml/min, NS). Following 24 hours changes in GCVF were still consistent only in Group 1 patients. Individual analysis during 24 hours showed marked fluctuations of GCVF peak values in Group 1 patients (62 +/- 43%), but not in Group 2 (29 +/- 21%). Thus, UK induces a marked increase of GCVF in most patients with anterior AMI; such increase suggests that reperfusion occurs early (i.e. within 1 hour) from UK administration. Fluctuations of GCVF during monitoring are magnified by thrombolysis, suggesting intermittent coronary reocclusion in the early hours of AMI. PMID- 1298552 TI - [Assessment of perioperative myocardial damage based on circulating heavy chain myosin fragments]. AB - To evaluate myocardial damage induced by coronary bypass surgery, to construct a reference data set in postoperative patients and to ascertain the impact of perioperative myocardial infarction on myosin release from sarcolemmal membrane we serially measured levels of serum fragments of myosin heavy chains by means of monoclonal antibody immunoradiometric assay (MYOSIN IRMA ERIA Pasteur). After surgery serum levels of myosin increased from third postoperative day and peaked on seventh day. Peak myosin levels did correlate with enzymatic activities of CPK (r = 0.69; p < 0.001) and of CPK-MB (r = 0.75; p < 0.001). Six patients suffered postoperative myocardial infarction: in these patients myosin levels were significantly different from those without infarctions (3651 +/- 1569 versus 699 +/- 206 ng/ml; p < 0.01). No correlation could be demonstrated between cardiopulmonary bypass time or aortic cross clamp duration. The rise of myosin levels observed in nearly all patients suggests a minor intraoperative damage to the contractile apparatus that sometimes is diagnosed as myocardial infarction and often does not meet clinical diagnostic criteria. PMID- 1298553 TI - [Calcium channel blockers inhibit human low-density lipoprotein peroxidation induced by oxygen free radicals in vitro]. AB - Previous studies have shown that calcium-antagonists may reduce the development of experimental atherosclerosis, and that nifedipine may slow progression of coronary atherosclerosis in man. The mechanisms responsible for this effect are still unclear. It has been recently proposed that oxygen-free radicals can induce peroxidation of human low-density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemical modified LDL are internalized by macrophages via specific cell surface receptor that was termed the scavenger receptor, and could induce foam cells transformation in vivo. Previous studies on other systems have shown that calcium-antagonists may effectively inhibit oxygen radical-induced lipid peroxidation. These drugs, though differing widely in their chemical structure, are lipophilic to various degrees and presumably would concentrate in the lipid domain of the phospholipid-rich membranes. Therefore, the aim of the present study was to investigate whether calcium-channel blockers may reduce human LDL peroxidation. Purified human LDL were exposed to oxygen radicals generated by xanthine-xanthine oxidase (18 hours) after a pre-incubation (30 min) in presence of different concentrations of nifedipine, diltiazem and verapamil. Peroxidation was measured from malonyldialdehyde production. The results show that calcium-antagonists prevent LDL peroxidation. Thus, calcium antagonists may reduce peroxidation of human LDL in vitro, at clinically relevant concentrations. These data suggest that reduced formation of atherogenic peroxidized LDL may be an additional mechanism for the anti-atherosclerotic effects of calcium-antagonists in vivo. PMID- 1298554 TI - [Variations in neuropeptide Y plasma levels in acute myocardial infarction]. AB - The aim of the study was to measure plasma neuropeptide Y (NPY) in patients with acute myocardial infarction (AMI). Eighteen patients (13 females and 5 males; range 55 to 75 years) admitted both early (n 12; mean preadmission time 3 +/- 2 hours) and late (n 6; mean preadmission time 25 +/- 16 hours) to Coronary Care Unit were studied. Plasma NPY values significantly above normal range (15-25 pg/ml) and early admitted patients (26 +/- 10 pg/ml) have been found in late admitted patients (72 +/- 28 pg/ml; p < 0.05) both on the admission and during the stay in the Coronary Care Unit (96 hours). In early admitted patients no significant correlation was found between both AMI localization and the thrombolytic treatment. A significant increase in plasma NPY levels has been observed in all patients with complicated myocardial infarction (both in subclinic and clinic heart failure or extension of infarct size). According with the literature data our results have shown a significant correlation between increase of plasma NPY levels and failure of myocardial pump. Moreover, the plasma NPY increase which has been observed in preclinic heart failure when plasma catecholamine levels is usually not significantly different from normal values, may be a useful and reliable prognostic marker. PMID- 1298555 TI - [Neuropeptide Y and heart failure]. AB - A time course (48 hours) of plasma neuropeptide Y (NPY) levels has been carried out in a male, 66 years old, admitted to Coronary Care Unit with inferior acute myocardial infarction within 1 hour from the onset of chest pain. On admission an increase of plasma NPY levels (38 pg/ml) has been observed. The plasma NPY value decreased to normal range (15-25 pg/ml) within 12 hours and increased again (53 pg/ml) within 12 and 24 hours. A decrease in plasma NPY values to normal range has been observed within the second day in the Coronary Care Unit. A clearcut diuresis decrease, without pulmonary signs of heart failure, was present from 12 to 24 hours followed by marked polyuria within the second day. These data point out a relative importance of NPY in the diuresis adjustments. Thus, plasma NPY measurement might be a more reliable prognostic indicator of heart failure than plasma catecholamine levels. However, further investigations have to be performed. PMID- 1298556 TI - Compliance as a major risk factor in periodontal disease progression. PMID- 1298557 TI - Over-the-counter and prescription mouthwashes-an update for the 1990s. PMID- 1298559 TI - Antibiotics in periodontal therapy: an update. PMID- 1298558 TI - Supragingival and subgingival irrigation: practical application in the treatment of periodontal diseases. PMID- 1298560 TI - Controlled local delivery of tetracycline in the treatment of periodontitis. PMID- 1298561 TI - Review of currently available battery-operated toothbrushes. PMID- 1298562 TI - Potential role of nonsteroidal anti-inflammatory drugs in the treatment of periodontitis. PMID- 1298563 TI - Serum fructosamine: a parameter for monitoring metabolic control in diabetes. AB - The aim of this study was to determine serum fructosamine in a non-diabetic population and to evaluate the usefulness of fructosamine in the routine management of diabetic patients. The range of serum fructosamine in the non diabetic population was 2.00-3.08 mmol/l (n = 300, mean 2.54 +/- 0.27). The mean level of fructosamine in the diabetic patients was 5.4 +/- 1.1 mmol/l at the beginning of the study and 3.5 +/- 0.4 mmol on the 12th week visit of the study. Significant differences in serum fructosamine levels were observed during the first visit and the 12th week visit p < 0.002. Serum fructosamine concentrations were significantly correlated with glycosylated haemoglobin at each subsequent visit (p < 0.001). No significant correlation between plasma glucose and fructosamine was found, suggesting the two parameters are markets for different time metabolic control. Routine use of serum fructosamine in management of diabetes is recommend. PMID- 1298564 TI - Aplastic anaemia: a review of cases at the University College Hospital, Ibadan, Nigeria. AB - Thirty male and 27 female patients were treated at the University College Hospital, Ibadan, over a 20 year period (January, 1971 to December, 1990) for aplastic anaemia. Age range was three months to 52 years with a median of 19 years. In 26 patients the aplasia could not be linked with a particular cause. Most patients in this category were students in secondary and tertiary institutions, office workers and casual labourers. Nineteen patients were automobile and factory workers who are exposed to lead while two were dealers in petroleum products. In two patients aplasia was linked to chloramphenicol ingestion while in three, the aplasia linked to the use of hair dye. Another three linked the aplasia to a past history of viral hepatitis. One patient had congenital aplasia of the marrow and one was a radiographer. Treatment included oxymethalone 100 mg given three times daily (tds) or intramuscular (i.m.) Durabolin 500 mg weekly. When these drugs were unavailable prednisolone 60 mg daily was administered. No patient had the benefit of bone marrow transplantation (BMT) or the superior drugs, e.g. anti-thymocyte globulin and cyclosporin A. This might have contributed to the poor prognosis as revealed by the survival pattern in which 24 patients died within six months of diagnosis while 19 survived 12 months. Seven patients died within 18 months and four others died within three years. Three patients were alive five years after presentation. Death generally resulted from complications of the aplastic anaemia with gastro-intestinal bleeding, cerebro-vascular accidents and overwhelming infections. PMID- 1298565 TI - The challenges of ambiguous genitalia. AB - In this paper, we assessed 71 patients between January 1985 and December 1990. Patients with ambiguous genitalia who were seen in the out-patient clinics of both the Paediatric and Urology Departments in the Harare Group of Hospitals. The majority of patients were seen by both the paediatricians and the urologists as children with anomalous genitalia, and a good number were referred to the Urological out-patients as cases of severe perineal, penoscrotal hypospadias, or cryptorchidism. Generally, there were three categories of patients who were seen. The first group were patients referred with severe hypospadias, perineal or penoscrotal and who only, after chromosomal studies, were then categorised into the ambiguous genitalia group. These patients were sent for chromosomal studies because of the concomitant cryptorchidism or, as they were suspected of having ambiguous genitalia because of the well developed labial folds without palpable testes. The second group of patients were patients seen at birth with incongruities which typify ambiguous genitalia. The third group was those who attended the urology clinics with a wish of having surgery performed to render their "phallic organ" long or good enough to help achieve rigidity for sexual intercourse. In the 71 patients seen, the classification had been made and surgery performed on a great majority of them at an early stage, to avoid later catastrophes and the possibility of the development of gonadoblastoma. PMID- 1298566 TI - Splenomegaly, malarial parasitaemia and anaemia in two Nigerian villages. PMID- 1298567 TI - Reproductive knowledge, and contraceptive awareness and practice among secondary school pupils in Bagamoyo and Dar-es-Salaam, Tanzania. AB - Reproductive knowledge, and contraceptive awareness and practice were assessed among secondary school pupils in Bagamoyo and Dar-es-Salaam, Tanzania. Four classes from four government secondary schools were randomly selected within strata of year of schooling, and students were interviewed using a structured questionnaire. All 490 pupils in selected classes participated in the study. Of 481 respondents with complete data, 315 (65.5 pc) were males and 166 (34.5 pc) were females; 256 (53.2 pc) were from Dar-es-Salaam while 225 (46.8 pc) were from Bagamoyo. Two hundred and ninety three (60.9 pc) respondents reported they were sexually active. However, only 77 (17.0 pc) pupils knew the "safe period" within the menstrual cycle and 329 (68.4 pc) pupils were able to spontaneously mention at least one method of contraception. Less contraceptive awareness was noted among respondents below 18 years of age particularly among females in both study areas. Only 45 (15.4 pc) pupils had ever used a contraceptive method. Despite a reasonable level of awareness and a positive attitude towards contraception, only a small proportion of sexually active pupils had ever used contraceptives. More research is required to identify the barriers to contraceptive use in the presence of knowledge. PMID- 1298568 TI - A clinical assessment of the consequences of alcohol consumption in 'communal' drinkers in the Zimbabwean Midlands. AB - The study was undertaken to clinically assess the consequences of alcohol consumption in 'communal' drinking patients whose levels of alcohol consumption could not be determined accurately in grams of alcohol. The level of alcohol consumed by 100 adult 'communal' drinking medical patients per drinking session was scored on a scale 0-10. The score was based on a qualitative impression of how much alcohol was drunk, level of consciousness, behaviour and gait. The frequency of drinking days in a week was scored on a 0-7 scale. The duration of drinking in years prior to registration at the clinic was also recorded. The pattern of diseases among the drinkers was compared to that of 70 adult non drinkers. The individual diseases were ranked to association with alcohol consumption by the Kruskal-Wallis Test. The drinkers attained a mean level score of 5.75 +/- 2.16, a frequency of 4.75 +/- 2.4 days but the duration of prior drinking varied greatly. Gout, dilated cardiomyopathy, epilepsy and hypertension ranked highest in that order to alcohol usage. Rheumatic heart disease and Diabetes mellitus ranked low. The probability significance were, for level score p = 0.005, frequency p = 0.016 and duration p = 0.001. This method was able to identify the morbid chronic medical diseases associated with alcohol usage in 'communal' drinkers. There is a need to evaluate it against a known screening instrument like the Alcohol Use Disorders Identification Test (AUDIT). PMID- 1298569 TI - Ethnicity, haemostasis and cardiovascular disease: the evidence from Africa. AB - Disorders of both coagulation and fibrinolysis contribute to the development of cardiovascular diseases such as coronary artery disease, essential hypertension, ischaemic stroke and deep vein thrombosis. Different ethnic groups, in particular Blacks, Whites and Asians have different prevalences for the above diseases. Comparisons of these haemostatic processes in different ethnic groups have contributed greatly to the understanding of the pathogenesis of many of these diseases. Such studies, in particular those conducted in Africa, are reviewed below. PMID- 1298570 TI - Major hepatic resection for secondary malignant tumours of the liver--case studies from eastern Nigeria. AB - Major hepatic resection (MHR) was performed in three patients with secondary malignant liver tumour (SMLT). MHR and extirpation of the primary cancer were done synchronously. There were two males and one female age 49, 52 and 65 years respectively. All were in liver functional Class B (Child's). Right hepatectomy and right hemicolectomy were done in one patient; while the others required: (1) left hepatectomy and middle colectomy in one patient; (2) left hepatectomy, middle colectomy total gastrectomy, splenectomy and middle colectomy in continuity in the last patient. They all tolerated the surgery and were discharged 16 to 24 days after surgery. Histology was adenocarcinoma in two patients and carcinoid tumour in one patient. One patient died 14 months after resection from recurrent tumour and liver failure. The other two patients have been followed up for 21 months and nine months. They are well and show no evidence of tumour recurrence. It is concluded that MHR is indicated in selected patients with SMLT. The short term and medium term results are better than the usual palliative management but case selection should be on criteria enunciated below. PMID- 1298571 TI - Comparing shower-based oral hygiene with traditional and electric toothbrushing. AB - Despite the importance of self-care for disease prevention, dentists and hygienists have been largely unsuccessful as oral hygiene motivators. Because of competing values, patients commonly fail to comply with prescribed oral hygiene regimens. In this investigation, attitudes of 84 adult dental patients were evaluated following a 30-day trial in which a shower-based oral hygiene system (SBOHS) was compared with manual and electric toothbrushing regimens performed in traditional settings. While attitudinal differences between manual and electric toothbrushing groups were insignificant, the SBOHS was perceived as substantially more enjoyable, convenient and reinforcing than either conventional or electric toothbrushing performed outside the shower. Significantly more SBOHS users reported spending more time on oral self-care, taking better care of their teeth and gums, feeling better about plaque control, appreciating oral hygiene practices more and perceiving cleaner teeth and a fresher mouth after oral hygiene than either the conventional or electric toothbrush users. PMID- 1298572 TI - Variability of two methods of measuring absorbed dose in dental radiography. AB - Thermoluminescence dosimetry (TLD) has been widely used in the monitoring of radiation exposure in healthcare workers operating radiation devices. This study compared the reliability of TLD to an electronic dosimeter. The absorbed dose registered by the TLD chips was found to be higher than that by the electronic dosimeter. Variability was found to be significantly higher and the variance component attributed to the variability of the method of measurement was more than twice as much in TLD when compared to the electronic dosimeter. It is concluded that TLD is a more variable method of measuring absorbed dose than the electronic dosimeter. PMID- 1298573 TI - Indirect pulp capping: a survey. AB - This study addresses the acceptance of the clinical practice of indirect pulp capping. State and regional dental boards and postgraduate dental education programs throughout the United States were surveyed. Results indicate that no clear consensus exists for the acceptance of this clinical procedure. PMID- 1298574 TI - In vitro demineralization inhibition of enamel caries utilizing an unfilled resin. AB - Smooth surface caries remain a concern in children, particularly those that are diagnosed with "baby bottle caries." The purpose of this study was to evaluate the caries inhibition of an unfilled resin placed on smooth enamel surfaces. Incisors were obtained and painted with an acid-protective varnish, excluding 2 mm x 6 mm windows on the labial surface. Each tooth had an unfilled resin placed over half the area of the window; the remaining area was not treated. One hundred microns longitudinal sections were obtained from the treated and non-treated sites. Polarized photomicrographs were taken of each section, in imbibition media of air, water and Thoulet's (R.I.: 1.41, 1.47), representing a minimum of 1%, 5%, 10%, and 25% pore volume respectively. The sections were then painted with an acid-protective varnish so that only the external surface was exposed and placed in separate closed environments of a non-fluoridated artificial saliva. One section from each tooth had unfilled resin on the external surface, one section had only natural enamel exposed, and a third section had the external surface varnished to act as a control. The teeth were thermocycled at 10 degrees C and 50 degrees C, 20 cycles per day for three months; they were also cycled through artificial caries challenge (pH 4.4) for 35 minutes, three times per day. Sections were then photographed under polarized light, as before, and areas of lesions were digitized. Results demonstrated caries to be present on all non treated enamel surfaces exposed to the artificial caries challenge. Significantly less enamel demineralization occurred when an unfilled resin was placed on it (p < 0.001). PMID- 1298575 TI - Enhancing flossing compliance in college freshmen. AB - This study examined the relationship between dental compliance and health locus of control in 41 college freshmen. Subjects were randomly assigned to either a control (N = 13) or experimental (N = 28) group. Dental flossing compliance was assessed in all subjects using a brief dental exam that assessed pocket depth and plaque as indexes of flossing behavior. The Multidimensional Health Locus of Control Scale was used to measure health locus of control. An educational, low fear intervention, consisting of the presentation of a pictorial diagram of the progression of periodontal disease and discussion of the importance of flossing was presented to the experimental subjects before monitoring began. Control subjects underwent a brief dental examination and flossing instruction only. Self reported flossing compliance was monitored for 24 days following the dental examination and intervention. Significant decreases in the dental exam variables associated with plaque were found for both the experimental and control conditions. The low-fear, educational intervention had no significant impact on compliance. Instead, a dental exam and self-monitoring were as effective at increasing flossing compliance as the more time-consuming educational approach. A significant increase in internality of health locus of control across all subjects was also found. No significant interaction was found between health locus of control and group, but a trend was apparent. Control subjects who were externally oriented had the lowest flossing compliance scores while internal subjects in both conditions had higher flossing compliance scores. PMID- 1298576 TI - Survey on AIDS, fear and infection control: attitudes affecting management decisions. AB - As a result of increased public concern about AIDS and dental treatment, dental professionals need to cope with legislative reactions, increased infection control costs, patient anxiety and vigilance on the part of law enforcement agencies regarding compliance with "universal precautions." Recommendations abound for educating patients about dental office infection control to allay irrational fears and market dental office asepsis, but few studies quantitatively measure these needs or address the behavioral concerns patients have about AIDS infection related to dental care. In this investigation, dental patients were surveyed to determine their beliefs, attitudes and behaviors regarding AIDS and dental office infection control. Several important educational caveats were identified. This paper considers these challenges and provides patient education and practice management recommendations consistent with a preventive focus on allaying dental patients' fears while building more successful dental practices. PMID- 1298577 TI - Clinical effect of a triclosan-containing dentifrice on plaque and gingivitis: a six-month study. AB - A total of 294 adult male and female subjects completed a 6-month, double-blind clinical trial designed to evaluate the effects of a dentifrice which contained 0.3% triclosan in conjunction with 2% of a methoxyethylene/maleic acid copolymer in a 0.243% sodium fluoride/silica base, relative to a control dentifrice, on supragingival plaque accumulation and gingivitis. Plaque and gingivitis were scored after 3 and 6-month use of the assigned dentifrice. At the end of the study, the triclosan group showed an average reduction, relative to the control group, of 12% in plaque accumulation and 20% in gingivitis. Both were statistically significant at p < or = 0.0001. The effect of the triclosan dentifrice was most pronounced on the more severe manifestations of plaque and gingivitis. The improvement in the gingival parameters at 6-months relative to the control dentifrice was statistically significant at p < or = 0.0001. It was concluded that the twice-daily use of the triclosan-containing dentifrice resulted in significant reduction in supragingival plaque formation and a significant improvement in gingival health without the presence of any extrinsic staining or objectionable taste. PMID- 1298578 TI - The pH volume changes of human red cells in vitro due to the exchange of chloride and hydroxyl anions. AB - In glucose exit experiments measured photoelectrically, the excursions on the chart recorder were found to be larger for exits in media of alkaline pH. This was shown to be due to the addition of a pH volume effect to that of the osmotic shrinkage resulting from the glucose efflux. The pH-dependent volume change also occurred in glucose-free cells and was a linear function of the pH of the medium between pH 6.8 and 9.0. The effect is consistent with the loss (or gain) of chloride in exchange for hydroxyl anions on the band 3 anion transporter and with the buffering of the hydroxyl anions by haemoglobin. The implications for the working of the anion exchanger and for respiratory physiology are discussed. PMID- 1298579 TI - Specific insulin binding by, and imprintability of, the nuclear membrane of Tetrahymena. AB - Cellular nuclei isolated from Tetrahymena were able to bind FITC-labelled insulin, and pretreatment with different concentrations of unlabelled insulin accounted for a decrease in FITC-insulin binding of the nuclear membrane. This strongly suggests an association of specific insulin receptors with the nuclear envelope of Tetrahymena. Nuclei isolated 1 week after primary exposure of Tetrahymena cells to insulin showed a 50% binding increase over the controls. This supports the implication that hormonal (insulin) imprinting also involves the receptors of the nuclear membrane of the imprinted cells. PMID- 1298580 TI - Evaluation of the genotoxicity of 4-N-butylamino-1,2,3,4-tetrahydroacridine hydrochloride (centbucridine): a new local anaesthetic. AB - Centbucridine, a new local anaesthetic, was tested in in vivo genotoxicity assays. Three different endpoints were selected for this purpose. Chromosome aberrations (CA) and sister chromatid exchange (SCE) were analysed in bone marrow cells and DNA-strand breaks (SB) were measured in liver cells of mice following a single acute exposure. No significant differences were observed in the CA, SCE and SB studies, when compared with respective controls. An increase in the mitotic indices (MI) was observed only with the lowest dose tested in the CA study. No significant differences in the MI were observed with the two higher doses tested when compared with solvent controls. Trend tests for linear dose response were negative in all the parameters examined including MI. The overall results of the three endpoints tested indicated that centbucridine was not genotoxic in the mouse. PMID- 1298581 TI - Effect of pretreatments (imprinting) with different concentrations of insulin on insulin binding of nuclear envelope and plasma membrane in Tetrahymena. AB - About 4 h following treatment with 10(-6) - 10(-10) M insulin (imprinting) there was a down-regulation both in the plasma membrane and in the nuclear envelope of Tetrahymena, i.e. there was a decrease in the binding value related to the control. In each concentration tested the imprinting resulted in increased FITC insulin binding after 24 and 48 h of treatment; the imprinting was independent of the concentrations. In the case of the plasma membrane the power of binding was directly proportional to the increase of the hormone concentration participating in the imprinting. For the nuclear envelope the optimal concentration was 10(-8) M. At very low concentrations (10(-10) M) the binding resulting in imprinting was insignificant in the plasma membrane but it was still present in the nucleus. PMID- 1298582 TI - Changes in proteolytic susceptibility of human erythrocyte membrane proteins during red blood cell aging. AB - The method employed facilitated analysis of the digestion of denatured proteins, depleted in their natural membrane environment. The susceptibility of human erythrocyte membrane proteins to digestion with trypsin was studied by the two dimensional electrophoretic method. Ghosts were isolated from erythrocytes fractionated according to density (age). Spectrin and band 3 protein from membranes isolated from the youngest cells were significantly more slowly degraded than proteins from middle-age cell membranes and from the oldest cells. PMID- 1298584 TI - [Hemodynamic effects of antihypertensive drugs on pregnancy-induced hypertension]. AB - Aiming to select a proper kind of antihypertensive drug for mild and moderate pregnancy-induced hypertension (PIH), 30 patients with PIH were examined by using noninvasive cardiovascular detector TP-CBS. The basic hemodynamic parameters included mean artery pressure (MAP) Kpa, heart rate (HR) bpm, cardiac index (CI) L min-1/m2 and total peripheral resistance (TPR) PRU. The 30 cases were divided into 6 groups with 5 each to take a single dose of prazoxin, phentolamine, methyldopa, captopril, nifedipine and aminophylline respectively. Hemodynamic parameters were examined consecutively every 30 minutes for 4 hours after ingesting the above drugs. The results showed that all the 6 medicines had effects of lowering MAP and TPR without change of cardiac output. Nevertheless, viewing from the effect of lowering blood pressure, change of pulse rate, time of action and incidence of side effects, we considered that nifedipine is superior to the other 5 and can be preferably recommended at outpatient clinic. PMID- 1298583 TI - [Monitoring of maternal-fetal hepatitis B virus transmission by molecular hybridization technique]. AB - Maternal venous blood (MB), umbilical blood (UB) and placental tissue (PT) were collected from 40 HBsAg positive mothers and their neonates, and also blood from 17 babies aged 3-6 months old of this group (BB). All samples were determined for hepatitis B virus (HBV) DNA by molecular hybridization technique using Bio-HBV DNA probe. The results showed: HBV DNA positive rate of MB was 35.0%, 47.5% for UB, 75.0% for PT and 29.4% for BB. 32 P-HBV DNA probe was also used to examine MB and PT. The positive rates of HBV DNA were 30.0% and 70.0% respectively. There was no significant difference between the results of the 2 probes. We considered: (1) With the rapid development of HBV detection technique, the detectable rate of intrauterine infection increases accordingly. (2) Besides transplacental infection, other transmission routes might be existed. (3) The detection of HBV DNA in UB, PT and in the blood of babies born by HBV DNA positive mother within 6 months old provides the reliable diagnosis. (4) HBV DNA molecular hybridization is an accurate and sensitive method for the diagnosis of HBV intrauterine infection. PMID- 1298585 TI - [Analysis of 930 cases of low birth weight newborns]. AB - The birth weight of 13,048 newborns were analyzed. The results showed: (1) The incidences of low birth weight (LBW) and very low birth weight (VLBW) were 60.10% and 11.19% respectively. (2) The perinatal mortality rates (PMR) for birth weight of < 1,500 g, 1,500-2,499 g and > or = 2,500 g were 465.8%, 127.60% and 5.30% respectively, (3) The causes of perinatal death included hypoxia, deformities, neonatal diseases and therapeutic induction of labour (38.80%, 25.86%, 22.84% and 12.50% respectively). The incidence of malformation in < 2,500 g group was 36 times of that in > or = 2,500 g group. (4) The incidence of LBW was significantly related to gestational age (P < 0.01). (5) The incidences of LBW among groups of various maternal age were significantly different, and the best age for childbirth was 25-29. (6) LBW was associated with mother's occupation, and LBW newborns from woman farmers were 5.8 times of those from intellectuals. (7) The PMRs differed significantly among groups of different maternal cultural background (P < 0.01). PMID- 1298586 TI - [Improving the curative effect of chemotherapy on gynecological malignant tumor by catheterization of internal iliac artery]. AB - Seventeen cases of gynecological malignant tumor received 27 infusion chemotherapy by selective catheterization via internal iliac artery. Among them, 14 cases (82.4%) were cancer of advanced stage. All of the cases were followed up. 77.8% of cases showed short-term good response. The intermittent mean duration without tumor growth was 12.5 months. The determination of platinum confirmed that the vascular embolism chemotherapy of tumor is one of the best approaches for pelvic tumors. PMID- 1298587 TI - [Assay of urine cysteine proteinase in diagnosing gynecological malignant tumors]. AB - Cysteine proteinases (CP) belong to the subclass of endopeptidase, and have been considered to play an important role in spreading cancer cells. Cysteine proteinases in urine (UCP) were determined in 71 healthy women, 76 patients with gynecological benign tumors and 125 cases (173 samples) with gynecological malignant tumors. Enzyme levels were assayed using the artificial substrate CSZ Ala-Arg-AFC by detecting the release of free AFC with the aid of a fluorometer. The value ranged from upper 80% to 99% of UCP in 71 normal women and was calculated with the percentile method. The results showed that ROC curve displayed a highly sensitive character. The sensitivity and specificity for gynecological malignant tumor were 91.8%, and 71.7% respectively. The sensitivities of UCP for ovarian cancer, cervical cancer, carcinoma of endometrium and cancer of vulva were 96%, 91%, 85.7% and 72.7% respectively. Due to its high sensitivity. It was suggested that UCP assay can be a good screening test to distinguish gynecological malignancy from benign tumors. The accuracy of diagnosing gynecological malignancy may be improved if UCP assay is combined with other tests with higher specificity. PMID- 1298588 TI - [A comparative morphometric and DNA content study of endometrial hyperplasia and adenocarcinoma]. AB - The DNA content and morphometric study of four groups of endometrial proliferations were compared: adenomatous hyperplasia (21 cases), atypical hyperplasia (13 cases), adenocarcinomas with superficially myometrial invasion (9 cases) and with deep myometrial invasion (8 cases). The normal DNA histogram patterns were identified in the majority of the adenomatous hyperplasia. The important difference between proliferative and neoplastic endometrium was the size and shape of nuclei of epithelial cells. The DNA content and morphometric measurement of atypical hyperplasia and well-differentiated adenocarcinomas were similar. The highest proportions of cells with polyploidy were found in the deep invasive carcinomas. The study suggests the DNA content determination and morphometry are useful supplementary methods for observing the continuous pathologic process. PMID- 1298589 TI - [Use-effectiveness of natural family planning by ovulation method]. AB - Cervical mucus (CM) peak and plasma LH surge were examined in 19 women. The consistency of the CM peak and ovulation after the plasma LH surge demonstrated that as an indicator of natural family planning (NFP), the CM can scientifically predict the occurrence of ovulation. Based on these results, 300 healthy women were recruited into this study by self examination of CM. A total of 3,393 cycles was observed. There were 29 pregnancies reported, and the continuation rate was 90.3/100 women year. It showed that the NFP is an acceptable, safe and effective birth control method for Chinese women. PMID- 1298590 TI - [Current status of epidemiologic research on endometriosis]. PMID- 1298591 TI - [A multi-center double blind prospective study of ridaura in the treatment of rheumatoid arthritis]. AB - 223 cases of definite rheumatoid arthritis were studied which were divided into ridaura treatment group and placebo group. Observations were made double-blind and prospectively. Judging from the comparison of therapeutic results of each treatment group on each clinical and laboratory parameters and of effective rate of each treatment group on the parameters and by comparing the physicians' and patients' assessments to the ridaura or placebo treatment, it was evident that the ridaura was much superior than placebo, possessing statistical significance. In physicians' assessment 14.2% failed to improve in the ridaura group but being 52% in the placebo group. Ridaura was a slow-acting drug, the earliest time for it to show clinical improvements being 2-4 months after medication. Adverse effects of ridaura were limited; incidence of loose bowel movements was much lower than that reported in the western countries. Among the 148 cases of the ridaura group, only two cases failed to complete the six months treatment course because of untoward reactions. PMID- 1298592 TI - [Role of enteric Klebsiella pneumonia infection and HLA-B27 in ankylosing spondylitis]. AB - Klebsiella pneumonia (KP) infection and HLA-B 27 have been shown to be strongly associated with ankylosing spondylitis (AS). In the present study, faecal cultures were performed and showed faecal carriage rate of KP was much higher in patients with AS (10/30) and hospital volunteers (2/10) than in the non-hospital volunteers (0/20). An octadecapeptide encompassing the shared hexamer between HLA B 27 and KP nitrogenase residue was synthesized and autoantibodies against this short peptide were detected in sera of patients with AS and Reiter's syndrome (RS) and other related disease and normal controls. The results showed that such autoantibodies were detected in 42.2% of AS and 30% of RS patients yielding positive rate much higher than those found in other control groups. It is concluded that enteric KP infection were strongly implicated in the pathogenesis of AS probably by the mechanism of molecular mimicry with HLA-B 27. PMID- 1298593 TI - [Endoscopic balloon dilatation for achalasia: an effect observation in 38 cases]. AB - From February 1988 to November 1990, thirty eight patients with achalasia were treated endoscopically with micro-vasive regiflex dilator (MRBD). Immediate success rate was 100% and the long-term effect 89.4%. No serious complications such as perforation of bleeding occurred. MRBD is superior to conventional dilators in treating this disease and probably the method of first choice. PMID- 1298594 TI - [Value and mechanism of abnormal postexercise systolic blood pressure response for detection of coronary artery disease]. AB - The value of an abnormal ratio of recovery systolic blood pressure to peak exercise SBP for detecting coronary artery diseases (CAD) is controversial. We evaluated the ratio in 39 patients with angiographically documented CAD and 52 patients with normal coronary artery undergoing treadmill exercise. If a response with the ratio higher than 1.0 and 0.8 at 1 and 3 min. of recovery was considered as abnormal, the sensitivity for detecting CAD was 66.7%, the specificity 73.1% and the accuracy 70.3%. If ST segment depression is combined into the criteria, the specificity and accuracy reach 94.2% and 76.9%. In CAD, the ratio at 3 min. of recovery showed significant negative correlation with resting left ventricular ejection fraction (LVEF) (r = -0.461, P < 0.01). It is suggested that low resting LVEF may be one of the mechanism of this abnormal ratio in CAD. PMID- 1298595 TI - [Bone histology and clinical diagnostic criteria in aluminum-induced bone disease]. AB - Bone remodeling and aluminum (Al) staining were carried out in 429 bone biopsies from patients with uremic bone disease, 273 cases were Al positive (64%). In high turnover, low-turnover and mixed type of renal osteodystrophy the Al-positive rate was 29%, 75% and 80%, and Al deposition on bone surfaces was 44 +/- 33%, 80 +/- 30% and 62 +/- 35% respectively. Thus the low-turnover and mixed type have a higher Al-positive rate and more Al deposition than the high-turnover type. Animal experiments using decalcified bone matrix implants showed that Al inhibited all bone remodeling processes except cartilage formation. These and other data indicate that Al induces low-turnover bone disease, i.e., osteomalacia or aplastic bone disease. Osteomalacia in our series showed increased osteoid area and mineralization lag time, and decreased calcified bone area, bone mineralization rate and cells number. Aplastic bone disease was similar with that but had reduced osteoid and a normal ratio of steroid to calcified bone. The relationship of these studies to clinical diagnostic criteria of Al-induced bone disease is discussed. PMID- 1298596 TI - [External pituitary irradiation therapy for acromegaly]. AB - 128 acromegaly patients were followed up for 1-23 years (mean 5.9 +/- 5.0 years) after external pituitary irradiation; among them 104 patients received fractional irradiation with an ultimate total dose of 4000-5000 rad. The remaining patients received a total dose of either < 4000 rad or > 5000 rad. Human growth hormone (hGH) level was measured after an oral load of 100g glucose to evaluate the effect of irradiation. After external pituitary irradiation, the serum level of hGH decreased progressively. The decrease was more rapid in the first three years with a decrement of 35.1% per year. 36.2% of all the patients has been judged as clinically inactive with low serum hGH level of < or = 5 ng/ml. 62.1% of the patients was considered as slightly active with hGH level < or = 10 ng/ml in the 15th year after therapy. The effect of irradiation was not influenced by the age of the patients, the course of acromegaly, the size of sella turcica and operation prior to irradiation. If the total dose of irradiation is lower than 4000 rad, the effect will not be good. PMID- 1298597 TI - [Monitoring of gentamicin blood level]. AB - A prospective randomized comparison of blood concentration as well as manifestations of ototoxicity and nephrotoxicity in groups with conventional and individualized administration of gentamicin was carried out in a total of 106 hospitalized patients. Therapeutic serum concentrations (peak 4-9 mg/L, though less than 1 mg/L) were achieved in 50% of the patients of conventional group and in all the patients of individualized group. Incidence of auditory and renal toxic reactions was high in the conventional group, being 27% and 30% respectively, while in the individualized group, the corresponding figures were 2.8% and 0%. Therefore, individualized administration of gentamicin based on data from therapeutic drug monitoring can markedly decrease the toxic effect and increase the therapeutic efficacy. It is worthwhile to use this kind of administration clinically. PMID- 1298598 TI - [Pulmonary angitis and granulomatosis]. AB - 16 patients of Wegener's granulomatosis, 4 of allergic angiitis and granulomatosis, 3 of lymphomatoid granulomatosis and 1 of necrotizing sarcoid granulomatosis were reported. In this group of different diseases, characteristic pathological manifestations are inflammatory cellular infiltration of vessel wall combined with destruction and necrosis of pulmonary parenchyma. There was little difference in their clinical features. In most of the cases, fever and systemic symptoms related to lung and extrapulmonary organs were present. Correct diagnosis of these diseases is very important, because both the prognosis and therapy are different. As for the prognosis, it ranges from benign (necrotizing sarcoidal granulomatosis) to very malignant (lymphomatoid granulomatosis). The clinical features of each illness were reviewed with emphasis on their histopathologic findings. The therapeutic effect and final outcome were followed. PMID- 1298600 TI - [Intervention measures for diabetes mellitus in community population]. AB - A prospective study was made of two randomly selected community population, one given diabetes mellitus intervention measures, the other as control. The results showed that the intervention group had significantly lower incidence of diabetes mellitus than the control group. It is suggested that a diabetes mellitus control program be tried with the municipal hospital as the centre in collaboration with primary health care units at the periphery. PMID- 1298599 TI - [The relation between gram-negative bacteria in intestinal tract, HLA-B27 and reactive arthritis]. PMID- 1298602 TI - [Study of cytogenetic damages in peripheral blood of styrene exposed workers]. AB - The three indices of chromosome aberration (CA), sister-chromatid exchanges (SCEs) and micronuclei were used simultaneously to ascertain the cytogenetic effects on eighty-three styrene exposed workers under current industrial hygienic conditions in two glass fiber reinforced plastics factories. Our results showed that exposure to styrene at a concentration of 129.3 mg/m3 (range 48.3-223.9 mg/m3) could result in an increase of the frequencies of CA and micronuclei but had little influence on the frequency of SCEs. PMID- 1298601 TI - [Preliminary observations on effect of selenium yeast on high risk populations with primary liver cancer]. AB - Two populations with high risk primary liver cancer (PLC), one of 226 cases with HBsAg carriers and another of 3849 first-relatives in the pedigree with high incidence of PLC, were randomly divided into the supplementing selenium group (selenium yeast 200 g Se1Tab/day) and the control group (common yeast 1 Tab/day), and were followed-up for four years and two years respectively. In the population with HBsAg carriers, no liver cancer occurred in the supplementing selenium group; where as the liver cancer incidence rate was 1573.03/10(5) in the control group. Among the first relatives. The liver cancer incidence rate in the supplementing selenium group was 219.37/10(5); and 553.15/10(5) in the control group. The results showed that the incidence of PLC in the supplementing selenium group was significantly lower than in the control group. This study indicates that selenium has distinct anti-PLC effect. PMID- 1298603 TI - [Effect of noise on blood pressure of various types of rats]. AB - Before the experiment, male Wistar rats were divided into two types (A and B) according to the different responses of their ECG and Heart Rate (HR) to 1 hour noise exposure: in type A, the ST segment elevated and HR decreased significantly during the exposure; in type B, both ST segment and HR showed no considerable variation. We exposed type A and B wistar rats and spontaneously hypertensive rats (SHRs) of 105 dB steady-state noise, 4 hours per day, 6 days per week. The results showed that after 3 weeks of noise exposure, the mean systolic blood pressure (BP) of type A rats was significantly higher than that of type B and control rats. This higher BP retained progressively till the end of observation (35 weeks); while there were not significant changes of BP in type B rats during the period of 35 weeks noise exposure. We also found that when exposed to noise for 14 weeks, the SHRs in exposure group had markedly higher mean systolic BP than those in control group. The results indicated that noise may affect BP of both Wistar rats and SHRs. There is probably a difference in the susceptibility of BP response to noise. The susceptibility of the BP of rats in type A to noise is greater than that of rats in type B. PMID- 1298604 TI - [Application of multistate model to the analysis of relationship between cumulative occupational exposure and occurrence of disease]. AB - The relationship between cumulative exposure and response used to be estimated by using the two state life table method. But since the occurrence of the response is related to the time factor after exiting exposure, this method may not provide correct description of this relationship. Based on multiple state model, this paper put forward a new method which modifies the effect of the time after exiting exposure on this relationship. The data from a cohort of 1113 underground male workers in a tin mine was taken as an example to illustrate the merit of this method. PMID- 1298605 TI - [Experimental study on selenium preventing nasopharyngeal carcinoma]. AB - In this study, we observed the effect of selenium (Se) on nasopharyngeal carcinoma (NPC) induced by dinitrosopi erazine (DNP) in rats through adding sodium selenite into drinking water. One hundred and sixty Wistar rats were divided into five groups: (1) blank control group (BG), no treatment; (2) Se control group (SG), given 50.7 mumol/L Se in drinking water for the first 3 weeks and then 31.7 mumol/L until the end of the experiment; (3) DNP control group (DG), injected subcutaneously 15mg/kg DNP twice a week from the 4th week to the 35th week; (4) Se prevention group (PG), given Se as done in SG and injected DNP as done in DG; (5) Se therapy group (TG), injected DNP as done in DG and given 50.7 mumol/L Se in drinking water from the 36th week to the end of the experiment. The experimental duration was one year. The result showed that there was no NPC in BG and SG and that the incidence of NPC in PG was reduced by 54.3% as compared with that in DG, which was significantly different (P < 0.01). In addition, the incidences of precancerous lesions of nasopharynx were significantly different between the two groups. But the incidences of NPC were not significantly different between TG and DG. In the process of carcinogenesis, the blood Se concentration of DG decreased. The blood Se concentration of rats could be elevated by supplementing Se in drinking water. Our result suggested that elevating the level of Se in rats can prevent the NPC. PMID- 1298606 TI - [Food poisoning caused by mouldy rice contaminated with Fusarium and T-2 toxin]. AB - An epidemic of food poisoning in human beings occurred in Tongxiang County, Zhejiang Province after eating mouldy rice contaminated with Fusarium and toxins. Continuous rainfall took place during the rice harvest season. The number of patients poisoned was 97, the rate of incidence was 58.8%. The incubation period was 10 to 30 minutes. The chief symptoms were nausea, dizziness, vomiting, chills, abdominal distension, abdominal pain and diarrhea. The fungi isolated from the mouldy rice were predominantly Fusarium heterosporum and F. graminearum. T-2 toxin was found in the mouldy rice and the highest content was 420 ppb. PMID- 1298608 TI - [Study on the incidence of coal mine pneumoconiosis and lung cancer in Beijing coal mining district]. AB - Thirty-two cases (20.13%) of primary lung cancer from 159 coal miner autopsies of Beijing coal mining area are reported in this study. The ratio of peripheral type to central type of lung cancer is 1.9:1; among them the adenocarcinoma is the most frequent (56.25%). Pathological examination shows that the diffuse interstitial type is the most common lung cancer. The occurrence of adenocarcinoma and the degree of lung fibrosis is related. The average number of ferruginous bodies is 190.2 +/- 8.06 in adenocarcinoma, 165.4 +/- 2.60 in squamous carcinoma, the difference is statistically significant (P < 0.05). The amount of trace elements-Fe, Al, Al/Si and Zn/Cu in lung with cancer is less than that without cancer. This article also discusses the relationship between coal mine pneumoconiosis with lung cancer of the formation of ferruginous bodies in the lung tissue of coal miner autopsies, which resembles the lung cancer combined with asbestosis. We also discussed the carcinogenesis of trace element in lung. PMID- 1298607 TI - [A study of vitamin inhibition on the mutagenicity of the antineoplastic drugs]. AB - The inhibitory effects on the mutational specificity of antineoplastic drugs of 14 kinds of vitamin were tested with the method of mutational and anti-mutational synchoronous test, add S9 and no S9. Vit C, Vit B6, and nicotinic acid had distinct inhibitory effects on the mutational specificity of 6 antineoplastic drugs, namely, mitomycin C, bleomycin, fluorouracil, cis-Diaminodichloroplatinum, arabinosylcytosine and mustargen Vit K3 showed inhibitory effect to mitomycin C, fluorouracil, cis-diaminodichloroplatinum, and arabinosylcytosine but Vit AD, Vit B1, Vit B2, Vit Bco, Vit D3, Vit E, Rutin, Vit K1, Vit K4 and folic acid did not. The fact that Vit C, Vit B6, nicotinic acid and Vit K3 showed anti-mutational effects is of some significance with reference to clinical therapeutics and prevention of tumours. PMID- 1298609 TI - [Comprehensive prevention of liver cancer]. PMID- 1298610 TI - [Current status and trends of the determination of fatty acids by chromatography]. PMID- 1298611 TI - Significance of bacteriuria in renal diseases. PMID- 1298612 TI - Bacteriuria in patients with glomerular diseases. AB - In a comparative study of significant bacteriuria in an African population, 1.7% of 697 healthy subjects (10 females and 2 males) were found to have positive urine cultures. Of these, 5 subjects grew E. coli, 4 Klebsiella strains, 2 Staphylococcus aureus and 1 Serratia marcescens. Among 116 patients with glomerular disease, 15.5% (7 males and 11 females) yielded positive cultures. E. coli, Staph. aureus and Proteus species were commonly isolated organisms. There was a nine fold increase in prevalence of bacteriuria in patients with glomerular disease and in females, this correlated with the amount of protein lost per 24 hours. It is postulated that the presence of protein in urine per se favours bacterial growth and because of the high prevalence of bacteriuria in patients with glomerular disease, it is recommended that all such patients should be screened and treated appropriately. PMID- 1298613 TI - Beef and dressed chickens as sources of enterotoxigenic Staphylococcus aureus in Nairobi. AB - Staphylococcus aureus (S. aureus) isolates from beef carcasses, minced beef, and dressed chicken were assayed for production of enterotoxin A, B, C and D using reverse passive agglutination technique. The highest isolation rate was from chickens followed by minced beef. Chickens yielded the highest percentage of enterotoxigenic strains. Staphylococcal enterotoxin C (SEC) was the most frequently produced type from all the three sources while enterotoxin A ranked second and enterotoxin B third. These data show that chickens and minced beef are potential sources of food poisoning staphylococci in Kenya, and that increased handling of the products increases contamination suggesting that man is the major source. PMID- 1298614 TI - In vivo effect of cadmium chloride on intestinal colonization of rats by Campylobacter jejuni. AB - Campylobacter jejuni (10(8) C.F.U) fed intragastrically unto 18 laboratory rats (white whiskers) resulted in colonization of the 18 rats intestines and their eventual excretion of the organism for four months post infection. When 10(8) CFU of C. jejuni was mixed with 10 mu/ml of cadmium chloride (CdCl2) and fed immediately to another set of 18 rats, colonization of rats intestines was greatly reduced and C. jejuni was recovered from two (11%) out of 18 rats and the faeces were positive for C. jejuni for a maximum of 29 days. Six control rats given 1 ml of phosphate buffered saline (PBS) and a second set of another six control animals given 1 ml of PBS containing 10 micrograms/ml of CdCl2 gave negative result for C. jejuni throughout the experiment. This work depicts an in vivo effect of CdCl2 on C. jejuni and may be of importance in the control of C. jejuni colonization in experimental animals. PMID- 1298615 TI - Household sanitation in Uasin Gishu district in Kenya. AB - In rural Uasin Gishu District in 1990, 78.2% of the households had pit latrines, 11.3% ventilated improved pit latrines, 0.8% water-borne and 9.7% with no toilet facilities. On inspection, 97% of the toilet facilities were in use. Compost pits were present in 52.3% of the households. Utensil drying racks were found in 56.0% of the households. Compared to previous estimates, these levels represent a tremendous improvement in sanitation service coverage. It is recommended that the impact of water and sanitation programmes on health status needs to be evaluated. There is a need for studies to be done on the value of utensil drying racks in disease control. PMID- 1298616 TI - Surgical treatment of chronic fissure-in-ano: a prospective randomised study. AB - A prospective randomised study compared anal dilatation (n = 37), posterior internal sphincterotomy (n = 21) and lateral sphincterotomy (n = 20) in the surgical treatment of chronic anal fissures in 78 consecutive patients. All the operations were performed under general anaesthesia using standard techniques. Anal dilatation relieved anal pain early (immediate relief in 57% of patients; the mean pain-days +/- SD of 3.2 +/- 5.4 days). Anal fissures after this operation healed in a mean time +/- SD of 20.3 +/- 12.5 days, coming in second place to lateral sphincterotomy. Anal dilatation was followed by insignificant wound infection but its main disadvantage was a high rate of post operative anal incontinence (in 24.3% of patients). Fissurectomy and posterior internal sphincterotomy was followed by the longest period of post operative anal pain (mean +/- SD of 32.4 +/- 10 days) as compared to the other two operations. It was the least favourable operation. Lateral sphincterotomy was followed by early relief of pain (immediate relief in 95% of patients). It was not followed by wound infection. It had the quickest healing time for the fissures (a mean +/- SD of 14.7 +/- 8.7 days). It was followed by anal incontinence in only one patient. In conclusion lateral sphincterotomy was the most favourable operation and it is perhaps the operation of choice to perform in patients with chronic anal fissures needing surgical treatment. PMID- 1298617 TI - Management of hand infection in Khartoum. AB - One hundred and fifty patients with hand infection seen during 6 months period at Khartoum Teaching Hospital were studied. The disease is more common among young males manual and industrial workers (M:F = 2:1). Common types of hand infections were paronychia in (41%) of patients, volar infections in (30.6%) and subcutaneous infections in (30%) of patients. 30% of patients needed hospital admission including all diabetics (n = 15). Two patients had serious complications that resulted in above elbow amputation. The first was a diabetic with spreading cellulitis and the second was a mentally retarded with gas gangrene. Initial empirical antibiotic therapy was prescribed in 89% of patients and later was modified according to sensitivity results. 90% of patients needed surgical drainage. Bacteriological examination showed Staph. aureus in 51% of cultures and the staphylococcus was resistant to penicillin in 77% of cultures. Apart from two deaths, the rest of the patients had satisfactory outcome. PMID- 1298619 TI - The pattern of morbidity and its effects on productivity of factory workers in Kenya. AB - A retrospective study was carried out from January to September 1990 in a factory that manufactures textiles in Eldoret, Kenya. Over the study period, 1400 factory workers had 303 episodes of illness resulting in a loss of 720 productive man days. This is an incidence of 289 episodes of illness per 1000 workers per year. On average, each episode of illness resulted in 2.4 man-days loss. Of all the episodes of illness, 58.8% were attributable to infective and parasitic diseases, 10.9% to respiratory system disorders and 21.7% to other conditions. Malaria constituted 53.1% of all episodes of illness, acute respiratory infection (ARI) 10.9%, physical injuries 5.6%, gastro-enteric illnesses 3.4% and other conditions 21.7%. For the productive man-days lost, 53.2% were attributable to malaria, 12.8% to ARI, 5.7% to physical injuries and 28.3% to other conditions. Abortions and worm infections resulted in loss of 7.0 man-days per episode of illness, diarrhoea 3.2, myalgia 3.0, ARI 2.8, eye diseases 2.7 and the rest below the average of 2.4 days. Apart from the physical injuries, there were no other occupational illnesses in the textile factory workers. Episodes of illness that occur during the last and the first week of the month constitute 61.0% of all illnesses. Mondays had 24.4% of the episodes of illness, Sundays 7.9% with the other days of the week constituting an average 13.5%. PMID- 1298618 TI - Observations from a cluster survey on seasonality in neonatal tetanus. AB - This report presents the observations on seasonality and neonatal tetanus (NNT) mortality from a cluster survey on NNT mortality conducted in Kano metropolis, Northern Nigeria. A two stage cluster sampling method was used for the survey. There were 2,623 live-births with 1778 (67%) occurring in the dry season (October May). The NNT mortality rate was 20.6/1000 live-births. The magnitude of neonatal mortality and NNT mortality were 47.3 and 30.8 per 1000 live-births respectively for the wet season. These were much higher than the comparative figures for dry season. There was, however, no significant association between seasonality and NNT mortality since the same trend was observed for non-NNT deaths. PMID- 1298620 TI - Sodium supplementation in very low birth weight infants fed on their own mothers milk: II. Effects on protein and bone metabolism. AB - We determined serum calcium, inorganic phosphate, alkaline phosphatase, total protein and albumin levels in a group of 66 very low birth weight (VLBW) preterm infants seen at Kenyatta National Hospital. We used these parameters as markers to study the effect of sodium supplementation on protein and bone metabolism in VLBW infants fed on their mothers' milk. 41 of the infants were supplemented with 3 mMol/kg/day sodium chloride for a duration of six weeks of postnatal life. The remaining group were fed only on their mothers' milk. Results indicated significantly increased serum levels of calcium (P < 0.01) in the non supplemented group while inorganic phosphate and total protein levels showed significant increase (P < 0.05) in the supplemented group. Both groups had increased levels of osteoblastic activity accompanied by high rate of protein synthesis in the supplemented group compared to the non-supplemented one. These findings together with a significant difference in growth rate (P < 0.01) observed between the two groups indicate that sodium supplementation may have a significant effect on the rate of bone mineralization and protein synthesis in VLBW infants. PMID- 1298621 TI - Skin sensitivity patterns to inhalant allergens in Nigerian asthmatic patients. AB - The pattern of skin sensitivity response to inhalant allergens in 746 Nigerian asthmatics and 92 normal controls tested over 10 years period is reported. Significant differences in reactions were observed in 7 of the 16 allergens routinely used in the study. House dust mite--dermatophagoides pteronyssinus gave the highest incidence of positive skin reaction, 58% asthmatics, 4.3% controls (P < 0.001). Other significant allergens were house dust 51.7%, feathers 24.4%; dog hair 12.9%, cat fur 11.9%, grass pollen 6.8% and flower pollen 6.3%. More males than females reacted to most of the allergens but this was statistically significant only for feather (P < 0.02). There was good correlation between history and skin sensitivity for most allergens. 82.3% of patients with positive skin test to D. pteronyssinus gave positive history of dust induced asthmatic attacks. Similar results were obtained for pollens: grass (86.3%), flower (83%) and feathers (57.7%). The correlation was however poor in respect of normal allergens (dog 30.6%, cat 36%). From the findings of this study there may be no point in routinely testing patients with a battery of allergens most of which may have no importance in the tropics. Attempts are however underway to incorporate local substances in skin testing materials. It is hoped that the results of this study will assist doctors who may not have access to skin test reagents in management of their asthmatic patients. PMID- 1298622 TI - Early and medium-term morbidity of minilaparatomy female sterilisation in Kenya. AB - A total of 1,521 clients undergoing voluntary surgical contraception via Minilaparatomy under local anaesthesia (L.A. Minilap) were prospectively followed up for early and medium-term morbidity. The commonest complaint was some degree of abdominal pain at 24.2%. Eight percent of these [corrected] reported that the operative pain was severe, but 92.0% reported minimal or moderate pain. The overall complication at 6 weeks was 4.1%, 17.5% of these were major and 82.5% minor, i.e. the rate for major complications was 0.7% and 3.4% for minor complications. There were no deaths. Female VSC via Minilaparatomy under L.A. is a relatively comfortable and easy procedure in well selected and counselled clients and carries minimal, usually non-recurrent morbidity. PMID- 1298623 TI - The changing pattern of intussusception in northern Nigeria: an analysis of 85 consecutive cases. AB - In many regions of Africa intussusception is the most common cause of intestinal obstruction next to strangulated hernia. More recent reports seem to indicate a change in the clinical pattern of the disease. This retrospective analysis covering a period of ten years is of 85 patients aged between 11 weeks and 50 years. There were 65 males and 20 females; 69 were children between 1 month and 15 years. The anatomical pattern of the disease has changed from being of the caecocolic type to the ileocolic variety while the pathology of the disease has remained largely unidentified. 32 patients had the ileocolic variety. 20 were ileocaecal, 14 colo-colic, 8 caecocolic, 8 ileo ileal, 2 jejuno jejunal, and 1 jejuno ileal. There were 2 ileal and 4 colonic neoplasms. There was a high rate of bowel resection (54/85) and 8 deaths. PMID- 1298624 TI - Complications of combined antiepileptic therapy. AB - Five hundred and fifty one epileptic cases in Taif Mental Health Hospital in Saudi Arabia were studied. Drug serum levels were determined by Enzyme Immunoassay. A combined anticonvulsant drug therapy was used frequently more than single drugs in the treatment of epilepsy. Percentage of combined therapy serum level was found higher than the therapeutic normal range of anticonvulsant drugs. Advantages and disadvantages of combined therapy as well as the importance of drug monitoring are presented. PMID- 1298625 TI - Re: Low dose hydralazine induced lupus. PMID- 1298626 TI - Radiation hazards in the developing countries. PMID- 1298627 TI - Radiation doses to patients during contrast examinations of the gastrointestinal tract. AB - Radiation doses received by patients undergoing radiological examinations of the gastrointestinal tract have been measured in 405 patients at two major hospitals in Nairobi using thermoluminescent LiF dosimeters. Skin-entry doses were found to be high at one of the facilities (A) and very high at the other (B). Barium meal delivered mean doses of 77 mGy (7.7 rad) and 558 mGy (55.8 rad) at facilities A and B respectively, while the corresponding mean values for barium enema were 93 mGy (9.3 rad) and 712 mGy (71.2 rad). Differences between the two hospital mean doses were highly significant (p < 0.001). Doses to the thyroid gland and the gonads were also generally higher than those reported in other similar studies. Poor performance of old and ill-maintained radiological equipment, among other possible factors, is suggested to be the main cause of excessive patient exposure. Radiation risks to patients are considered in the context of such high doses being received by a generally young patient population. The authors suggest that there ought to be limits on the extent to which social and economic considerations in the provision of radiological services should be allowed to compromise sound principles in the radiation protection of the patient. It is recommended that increased efforts be directed at establishing and supporting quality assurance programmes for the performance testing of radiological equipment in Africa. PMID- 1298628 TI - Neurological complications of sickle cell anaemia at KNH: a five year retrospective study. AB - In a five year retrospective study of 360 patients with homozygous (SS) sickle cell disease, eighteen (5%) were found to have neurological complications. Their ages ranged from 7 months to 21 years with a mean of 11.1 +/- 6 years. Of those with neurological complications, twelve (67%) of the patients had cerebrovascular accident, six (33.3%) convulsions, three visual disturbance; one sensorineural deafness, one cerebellar degeneration and the last one confusion and hallucinations. Four of the patients had multiple neurological complications. There was only one patient with recurrence of neurological complications. Two patients were hypertransfused and up to the end of the study period none of them had any recurrence. The pattern of neurological complications are similar to that observed in other studies. However, in this study, there were fewer recurrences of neurological complications. PMID- 1298629 TI - Abnormal eating attitudes among a group of Nigerian youths: I. Bulimic behaviour. AB - The prevalence of bulimic behaviour, a form of abnormal attitude to eating, was investigated among three different samples of Nigerian youths. Using the Binge Eating questionnaire, a total of 649 females comprising high-school (n = 196), university undergraduate (n = 333) and college of education (n = 120) students were surveyed. A significant proportion of the total student population engaged in bulimic behaviours of bingle-eating (21.16%) and vomiting (22.20%). The various weight control methods they used include diet pills (4.70%), diuretics (6.60%), laxatives (19.50%) and vomiting (26.20%). These findings suggested that bulimic behaviour may be as much a non-western phenomenon as it is a western phenomenon. PMID- 1298630 TI - Abnormal eating attitudes among a group of Nigerian youths: II. Anorexic behaviour. AB - A survey of a total of 644 female Nigerian high-school, college and university undergraduate students was conducted to examine abnormal eating attitudes associated with anorexic behaviour. Using a cut-off score of 20 on the Eating Attitudes Test-26 (EAT-26), overall prevalence of disordered eating attitudes was found to be 14.1%. Prevalence figures for the high-school, university, and college samples were 18.6%, 9.1% and 21.7% respectively. These findings are comparable to those from western countries and suggests that nowadays abnormal eating attitudes associated with anorexia behaviour may be a universal phenomenon that transcends cultural boundaries, contrary to the earlier notion that they were restricted to western countries. PMID- 1298631 TI - Quinine loading dose in severe Falciparum malaria at Kenyatta National Hospital, Kenya. AB - From July 1989 to February 1990, 17 non-pregnant patients with severe falciparum malaria, aged 14 years and above received an initial intravenous quinine dihydrochloride loading dose of 20 mg/kg in 500 mls of normal saline or 5% dextrose infused over 4 hours followed by 100mg/kg infused 8 hourly for at least 24 hours. Sixteen comparable controls were similarly treated but without an initial loading dose. Oral quinine bisulfate 10mg/kg 8 hourly was substituted for a total of 7 days when patients were well enough. There was no significant difference in clinical and parasitological response between the two groups. Fever clearance time in hours was 44.00 +/- 13.92 (mean +/- SD) in the study group and 51.43 +/- 19.63 (mean +/- SD) in the control group (p > 0.05). Parasite clearance time in hours was 42.40 +/- 9.75 (mean +/- SD) in the study group and 47.05 +/- 7.69 (mean +/- SD) in the control group (p > 0.05). One patient from each group died. Mild toxic effects were common in both groups. Transient partial hearing loss occurred significantly more in the study than control group (p < 0.05). Hypoglycaemia during treatment occurred in 3 (18%) patients in the study group and 1 (6%) in the control group. The mean trough and peak plasma quinine levels in 3 patients per group was persistently higher than 9mg/L after first infusion. We conclude that though fairly well tolerated, quinine loading dose appears to have no advantage over the standard treatment for severe falciparum malaria at Kenyatta National Hospital, Nairobi, Kenya. PMID- 1298632 TI - Maternal mortality in the Thyolo District of southern Malawi. AB - The Sisterhood Method, a community-based survey technique, was used to estimate the Life Time Risk of a woman dying a maternal death in Southern Malawi. With this figure, the maternal mortality ratio for that area was calculated to be 409 deaths per 100,000 live births. The 4124 adults interviewed reported 150 maternal deaths in sisters. An in-depth questionnaire was then used to determine that 56% of these deaths occurred outside a health facility, largely due to lack of transportation or poor access to fixed health care facilities; 25% died from excessive hemorrhage; 20% from obstructed labour; 18% from abortion; 13% from sepsis; while eclampsia accounted for only 4% of the maternal deaths. This field experience with the Sisterhood Method technique combined with an in-depth questionnaire for determining causes of maternal deaths has provided useful information in a simple and cost-effective manner for use in planning intervention strategies designed to decrease maternal mortality. PMID- 1298633 TI - Efficacy, tolerability and safety of isradipine (Lomir) in the treatment of mild to moderate Tanzanian hypertensives. AB - Isradipine (Lomir) a new dihydropyridine calcium antagonist was evaluated for its efficacy, tolerability and safety among mild to moderate Tanzanian hypertensives. Twenty nine patients (7 males and 22 females), mean age 42.7 +/- 8.5 years entered active treatment phase, of the 16 week open label therapeutic trial. A mean decrease from base line in supine systolic blood pressure (SBP) of 17.6 mmHg (p < 0.001) and diastolic blood pressure (DBP) of 13.5 mmHg (p < 0.001) were achieved at the end of the study period. The corresponding changes from base line in standing SBP and DBP were 18 mmHg (p < 0.001) and 13.5 mmHg (p < 0.001) respectively. The efficacy was excellent or good in 84% and fair or none in 16% of the study patients. The tolerability of the drugs was excellent or good in 88.8% of patients, fair in 7.4% and bad in 3.8%. The mild side effects included headache, palpitations, tiredness and nocturia. But these improved with continued treatment. Isradipine (Lomir) at a dose of 1.25mg to 2.5mg twice daily is effective, safe and tolerable in mild to moderate hypertension. PMID- 1298634 TI - Risk factors for HIV infection in gynaecological inpatients in Dar es Salaam, Tanzania, 1988-1990. AB - A prevalence of 12.8% for anti-HIV-1 and a prevalence of 16.8% for anti-syphilis antibodies was found in 359 gynaecological inpatients admitted in the Department of Gynaecology and Obstetrics, Muhimbili University College of Health Sciences from 1988 to 1990. The highest HIV prevalence (17.3%) was observed in the youngest age group (14-20 years), whereas the highest syphilis prevalence (22.2%) was found in the oldest age group (> 45 years). Infections with HIV and syphilis were both significantly associated with variables related to sexual behaviour, such as marital status, age at first intercourse and number of sexual partners in the past ten years. After adjustment for these common risk variables linked to sexual behaviour, syphilis infection was still associated with a more than twofold higher risk of HIV infection (odds ratio (OR) = 2.60, p = 0.02) and trichomonas vaginalis infection with a nearly threefold higher risk (OR = 2.96, p < 0.001). These data characterize patients at risk for HIV infection among inpatients of a gynaecological department in East Africa, and indicate that effective measures to prevent sexually transmitted disease may reduce HIV transmission. PMID- 1298635 TI - Some characteristics of serum phenytoin concentration, in black Zimbabwean volunteers. AB - A study of phenytoin pharmacokinetics in 15 black healthy Zimbabwean volunteers with an average age of 22 to 44 years was performed. A dose of 200 mg (capsules) sodium phenytoin was administered orally to each subject. Peak phenytoin serum levels were detected six hours post-dosing at 2.98 +/- 0.53 micrograms/ml. The mean elimination half life (t1/2) was calculated at 40.2 hours with a range of 36.7 to 40.5 hours. The area under the curve was calculated to be 142.5 with a range of 118 to 192. Comparison of our results with those obtained by other workers is discussed. PMID- 1298636 TI - Finger amputations in Tanzania. AB - A survey of finger amputations carried out at Dodoma Regional Hospital, has shown that from 1983 to 1991, a total of 147 amputations have been done on 101 patients. They have been performed, mostly for causes that relate quite well with the living and working conditions of the inhabitants of Dodoma Region. Western causes of finger amputations have been responsible of ablation in a few patients in our series. Finger infection, usually with bone involvement, has been found to be the leading cause, followed by traumatic injuries, human bites and burns. Most patients were peasants, with a good number of illiterates among them, drawn from rural areas. They came late to hospital having been improperly managed in the early stages of the diseases. All these factors explain quite well why finger infections were, on admission, irrecoverable through medical means. PMID- 1298637 TI - Allergic conditions in a general practice in Nairobi: a pilot study. AB - This is a study of 574 randomly selected patients seen in a private practice. The incidence of allergic conditions was found to be 18.8%. The distribution of the allergic conditions was as follows: 35 suffered from bronchial asthma, 33 had dermatological allergic conditions, and 30 were reported as having drug allergies. A significant number of these patients had multiple allergic conditions. PMID- 1298638 TI - Determination of foetal sex by ultrasound: state of the art. AB - The determination of foetal gender is clinically indicated in sex-linked disorders. The reliability of ultrasound in prediction during the late second and third trimesters is well-established. Few studies attained high success rate in early second trimester. The variations in the success rate are due to the difference in size and gestational age of the published samples. Most studies have concentrated on the visualization of the external genitalia. Differentiation based on internal organs is not pursued. The ethical aspects have received attention by almost all workers in this field. PMID- 1298639 TI - Effects of phosphate in the production of hemolysin in Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus is known to produce several types of hemolysin, the most document is the TDH and TRH. A new type of hemolysin whose expression is repressed by the presence of phosphate in the medium is reported. PMID- 1298640 TI - Oral herpes simplex virus type 1 infection following cadaveric renal transplantation in a young type 1 diabetic female. The role of acyclovir: a case report. AB - Oral infection with Herpes Simplex Virus (HSV) is a frequent and well documented complication in immunosuppressed individuals including patients on immunosuppressive medication. We report the development of severe oral infection with HSV type 1 in a 34 year old woman with type 1 diabetes mellitus and end stage renal disease (ESRD) following cadaveric renal transplantation at the Western General Hospital, Edinburgh. The role of acyclovir in therapy and chemoprophylaxis is discussed. PMID- 1298641 TI - Microbiological aspects and technological need: technological needs for nitrates and nitrites. AB - Nitrate and nitrite are used in meat and fish curing, and in the manufacture of certain cheeses. Nitrate itself has little antimicrobial effect and in most applications could be replaced by lower concentrations of nitrite. Further, improved hygiene diminishes the need for nitrite. The antimicrobial activity and technological needs for nitrate and nitrite are reviewed. It is concluded that the technological needs for nitrite in meat products stored at < 10 degrees C could be met by added nitrite concentrations of 50 mg/kg. The overall effect of nitrate in salted fish appears to be marginal. In such products, Vibrio parahaemolyticus does not grow at salt concentrations of 10% and food poisoning by this organism is not related to the absence of nitrate or nitrite; growth of Clostridium botulinum Type E (the predominant cause of botulism from fish products) is arrested by salt concentrations of 3-4%. Listeria monocytogenes in seafood cannot be controlled by nitrite. The use of nitrate in cheese production could be avoided, or at least reduced to a low level by avoiding silage with a high count of gas-producing Clostridia and hygienic milk collection. PMID- 1298642 TI - Properties and use of sulphur dioxide. AB - This work analyses comprehensively the mechanism of action of sulphur dioxide in the process of wine-making. The use of sulphur dioxide is still a necessity for the storage and preservation of white wines. Nevertheless, the study of its physico-chemical and antimicrobial properties can make possible a large reduction of doses used even for white wines. PMID- 1298643 TI - Inactivation of Yersinia enterocolitica by nitrite and nitrate in food. AB - The antimicrobial effects of sodium nitrite and sodium and potassium nitrate against Yersinia enterocolitica were investigated in solution and in treated pork meat. Potassium nitrate and sodium nitrate showed only feeble antimicrobial activity in cultures; no antimicrobial activity was detected with sodium nitrite. Conversely, all three salts displayed apparent antimicrobial activity in pork meat, possibly due to selective effects on competitive flora. PMID- 1298644 TI - Food irradiation: is it an alternative to chemical preservatives? AB - Generalizations about effects of irradiation may be misleading if the dose and commodities are not specified. Irradiation could be used for inhibition of sprouting, disinfestation, destruction of parasites in meat, to delay maturation of fruit and for pasteurization and sterilization. In some applications it could replace chemical sprout inhibitors, fumigants and chemical preservatives; in other cases it may have unique advantages e.g. in eradication of non-spore forming pathogens in dry or frozen foods. Toxicological and nutritional evaluation has repeatedly confirmed the safety of irradiated foods. Effects on nutritional quality are frequently comparable with heat treatment and sometimes more conservative, particularly if oxygen is excluded. While food irradiation could be an alternative to chemical preservatives, misinformation has led to uncertainties as to its future. PMID- 1298645 TI - Effect of some food preservatives on aflatoxin production. AB - The effect of some food preservatives, such as sorbic (SA) and propionic (PA) acids, on aflatoxin production in synthetic media or in moistened (20%) wheat seeds, was investigated. The preservatives tested, added to synthetic media at sublethal concentrations both at the inoculum and after 5 days of incubation, stimulated aflatoxin production by Aspergillus parasiticus. Sorbic and propionic acids are metabolized by the fungus in vivo and in vitro. Lower concentrations of PA and SA (0.05 to 0.1% w/w) in wheat seeds are ineffective against both fungal growth and aflatoxin production, whilst the combined use of butylated hydroxy toluene (BHT), and PA or SA was more effective in controlling aflatoxin production than their use as single components. PMID- 1298647 TI - Surveillance of preservatives and their interactions in foodstuffs. AB - The organization of food surveillance in the UK is described, in particular as it has been applied to preservatives and their interaction products in foods. Applications of nitrates and nitrites as preservatives are discussed, together with the consequential exposure of consumers to these anions and their reaction products. Analytical methods for the determination of volatile and non-volatile N nitroso compounds are referred to in relation to the results in food surveillance studies. Concentrations of Apparent Total N-nitroso Compounds (ATNC) averaged 2900 micrograms(N-NO)/kg in fried smoked bacon compared with 2400 micrograms/kg in fried unsmoked bacon; of this, known volatile and non-volatile N-nitroso compounds accounted for only 10-20%. ATNC were not detected in cheeses except those manufactured with added nitrate when ATNC levels up to 210 micrograms(N NO)/kg were detected. Further studies are needed to determine the identity and toxicological properties of the non-volatile N-nitroso compounds. PMID- 1298646 TI - Lysozyme: just an additive or a technological aid as well? AB - The effects of lysozyme on coagulation of milk and cheese making were studied by means of the gelograph, tristimulus colorimetry, ANS-fluorescence (hydrophobicity) and SDS-PAGE. Lysozyme binding to caseins caused structural differences during coagulation and it is proposed that, if the products have similar qualitative properties, lysozyme might be used as a technological aid giving shorter clotting times and higher yields. PMID- 1298648 TI - Reactions of nitrate and nitrite in foods with special reference to the determination of N-nitroso compounds. AB - The stabilities of nitrate and nitrite in food systems and their reactions in such matrices are reviewed. Particular reference is made to reactions with haem proteins, smoke components and amines in foods, and the chemistry of formation of N-nitroso compounds from food components is discussed. Finally, the methodology available for determination of both volatile and non-volatile N-nitroso compounds is addressed. PMID- 1298649 TI - Chemistry of sulphiting agents in food. AB - The main reason for the reactivity of sulphites in food is the nucleophilicity of the sulphite ion. The factors which determine the activity of this nucleophile are summarized and critically evaluated for concentrated systems, e.g. dehydrated foods. The distinction between free and bound sulphite is explained, and reversible binding of the additive in beverages and dehydrated foods is discussed with reference to simple theory of chemical equilibrium. The inhibition of non enzymic browning reactions accounts for a large proportion of sulphite which undergoes irreversible reaction in concentrated foods. The mechanisms of reactions between sulphite species and intermediates in the model Maillard reaction, glucose+glycine, are considered in depth together with supporting kinetic data. An interesting feature is the fact that sulphites seem to catalyse the reactions they are added to control. Implications of this to the level of use of sulphite are discussed. Reaction products from the inhibition of Maillard browning include 3,4-dideoxy-4-sulphohexosulose which is formed initially and polymeric substances which arise from the reaction of sulphites with melanoidins. A proportion of sulphite added to food becomes converted to sulphate. Mechanisms of autoxidation are critically appraised in view of the presence of considerable concentrations of antioxidants in foods. The autoxidation of sulphite involves reactive free radical intermediates which include effective oxidizing agents. Thus, a pro-oxidant effect by the additive is possible and demonstrable in model system experiments. PMID- 1298650 TI - Kinetics and mechanism of the reaction between 3-deoxyhexosulose and thiols. AB - The kinetics of the reaction of 3-deoxyhexosulose, DH, with mercaptoethanol, ME, and glutathione, GSH, resemble those of the DH-sulphite reaction, but the stoichiometry of the DH-thiol reaction is 1:2 unlike that of the DH-sulphite reaction which is 1:1. However, the rate determining step in all these reactions is the spontaneous conversion of DH to a reactive intermediate, followed by a rapid reaction of this intermediate with the nucleophile. This is also true of the reaction between DH and N-acetylcysteine, NAC, but this thiol is less reactive than ME or GSH and less than one mole of NAC reacts with each mole of DH. Evidence for instability of NAC at pH 5.5 is presented. Aminothiols (cysteine, homocysteine, cysteamine) undergo a fast reaction with DH followed by a slow release of thiol. The initial reaction is probably formation of a thiazolidine. In the case of cysteine and homocysteine it is suggested that the subsequent slow step is a Strecker degradation reaction. The kinetic behaviour of thiols in cabbage homogenates is reported. PMID- 1298651 TI - Kinetics of the inhibition of ascorbic acid browning by sulphite. AB - Despite differences in the structures of aldoses and ascorbic acid, ASA, the non enzymic browning of the latter involves intermediates similar to those found in Maillard browning. The kinetics of the sulphite-inhibited browning of ASA suggest that, under anaerobic conditions, the rate of reaction of sulphite species, S(IV), is of first order with respect to S(IV). The possibility that S(IV) could catalyse the hydrolysis of the lactone ring of ASA is considered by reference to D-glucono-delta-lactone. Evidence is presented to suggest that, under aerobic conditions, autoxidation of ASA leads to the oxidation of S(IV). The composition of melanoidins from ASA-glycine mixtures is compared with that from arabinose glycine; the former contain 2 x 5 times more ASA-derived residues per glycine molecule than arabinose-derived residues per glycine molecule in the latter. The implications of these findings to the mechanism of ASA browning are discussed. PMID- 1298652 TI - Kinetics of the sulphite-inhibited browning of fructose. AB - Sulphite species, S(IV), inhibit the non-enzymic browning of fructose-amino acid mixtures. Inhibition of browning is accompanied by a loss of S(IV). The kinetics of the reaction of S(IV) in the system: fructose-glycine-S(IV) are described in detail; two distinct mechanisms have been identified. One involves only fructose in the rate determining step. The other requires fructose and both the glycine and S(IV). Some amines (e.g. taurine and ethanolamine) can markedly increase the rate of the S(IV)-independent step. Arginine and lysine are particularly effective for increasing the rate of reaction of S(IV) in the S(IV)-dependent reaction. PMID- 1298653 TI - Kinetics of the reaction of sorbic acid with sulphite species. AB - Under aerobic conditions, the reaction of sorbic acid with sulphite species, S(IV), involves a pH-dependent oxidative mechanism with the loss of S(IV). Sorbic acid is essential to the process. In the absence of air, a much slower nucleophilic addition of sulphite ion to undissociated sorbic acid takes place. PMID- 1298654 TI - Reaction of sorbic acid in wheat flour doughs: reaction with thiols. AB - The general characteristics of the reaction between sorbic acid and thiols are reviewed. Cysteine adds to the conjugated diene in position 5 to form the substituted 3-hexenoic acid. This is labile in acid solution, yielding a quantitative amount of sorbic acid. When wheat flour doughs are treated with sorbic acid and heated, a significant amount of the sorbic acid is not recovered on extraction with methanol. The use of acidified methanol leads to a quantitative recovery of the preservation and evidence is presented to suggest that sorbic acid-thiol adducts are formed. This is the first report of 'reversibly bound' sorbic acid in a food. PMID- 1298655 TI - Browning prevention in fresh and dehydrated potatoes by SH-containing amino acids. AB - N-Acetyl-L-cysteine and reduced glutathione were excellent inhibitors of browning of potatoes. In most cases, these two SH-containing compounds were more efficient inhibitors than L-cysteine and approached the effectiveness of sodium sulphite. These considerations suggest that N-acetyl-L-cysteine and reduced glutathione merit extensive evaluation as potentially useful inhibitors for food products. PMID- 1298656 TI - Rapid method for the simultaneous GC quantitation of acids and sugars in fruits and vegetables. AB - Rapid methods of analysis for the simultaneous determination of acids and sugars in fruits and vegetables using trimethylsilylation and gas chromatography are reported. The methods have been shown to be generally applicable, rapid, simple and cheap. Typical applications are shown involving the determination of a range of organic acids and sugars in carrot, potato, cucumber, tomato, apple, pear, grape, strawberry and citrus fruits. PMID- 1298657 TI - Nutritional aspects of food preservatives. AB - Despite the benefits attributed to food preservatives, some concern still remains regarding their safety and possible influence on nutrients. Surprisingly, there is quite a lack of scientific knowledge in this field. In order to describe a few examples, the effects of the extensively used sulphite on thiamine, folates, pyridoxal and other nutrients have been reported. Among its antibrowning effects, inhibition of ascorbic acid browning is also considered. As far as sorbic acid is concerned, notwithstanding its easy reaction with protein, probably the acid environment of the stomach determines the breakdown of the sorbic-protein adducts. Detoxication of nitrite by tocopherol and ascorbic acid leads, in the last case, to dehydroascorbic acid and its oxidative products with loss of vitamin activity. Any oxidizing substance destroys ascorbic acid, vitamin E and free vitamin A. Phosphates are largely used with different aims, including preservation, in food processing. Their antimicrobial activity is due to both a direct effect and an interaction with other antimicrobials. Sequestering capacity of phosphates and its nutritional implications are discussed. Also mechanisms of action of organic acids are reported, focusing on sorbic acid effects on single amino acids and proteins. Finally, the little information available about the potential impact of food preservatives on nutritional functions is presented. PMID- 1298658 TI - Estimates of intakes: methodology and results of some studies carried out in Italy. AB - The methods which may be applied to estimating population intakes of food additives are outlined. The applications in studies of the intakes of some preservatives and food colours in Italy are reported. It was concluded that there is a need to investigate comparability between the various methods used. The surveys carried out indicated that, in general, the levels of consumption of the additives studied did not present a health risk. PMID- 1298659 TI - Food additives intake. AB - The role of intake studies in the safety assurance process is discussed with reference to food preservatives and related to the variations in the authorizations for use. PMID- 1298660 TI - Estimation of sulphite in food in France. AB - Estimates have been made of the consumption levels of sulphites in foods in France using two methods, a global and a segmented protocol. The global method gave an estimated average intake of 20 mg SO2/day/capita; the segmented method gave estimates of 1.96 mg/day/capita for non-consumers of alcoholic beverages and 31.5 mg/day/capita for average consumers of cider, beer and wine. The risk of exceeding the Acceptable Daily Intake concerns only regular consumers (40-75 years old) of alcoholic beverages, particularly wine, the main vector. The global approach appears to be a simple and useful method for estimating intakes. PMID- 1298661 TI - In vitro model for the evaluation of toxicity and antinutritional effects of sulphites. AB - The food preservatives, sulphur dioxide and its salts, are known to present some toxic, mutagenic and antinutritional effects; in fact they interact with a number of nutrients, e.g. some vitamins, notably thiamine (Th) and folic acid (FA). The effect of different concentrations of sodium bisulphite in cell culture media has been studied in vitro on a human cell line, HEp-2, deriving from a carcinoma of the larynx. Moreover, the sulphites have been tested with different levels of Th and FA with the aim of elucidating how much the cellular response depended on either the anti-nutritional effect or the toxicity of sulphites. Cell growth has been taken as an index of cytotoxicity and measured both as total protein content and as colony-forming ability. With no Th and FA in the culture medium, a clear decrease of cell growth was observed either with or without addition of sodium bisulphite. A dose-dependent reduction of protein content was detected in cells treated with 10, 50, 100, 200, 250 or 500 microM sodium bisulphite. Moreover, when the cells were treated with 10 or 100 microM of this compound, the colony forming ability was reduced both in number and colony size. As far as the interaction of the two vitamins with sodium bisulphite is concerned, when these nutrients were present in the medium at 0.5, 1.0, 1.5, 2.0 or 2.5 mg/l, a similar growth profile, determined from their concentration, was observed in treated and control cells, the growth levels being affected by the sodium bisulphite contents. At higher levels of Th and FA, the growth index was still increasing only in treated cells, this phenomenon being particularly evident in cultures treated with 200 microM sodium bisulphite. The colony-forming ability was reduced in controls but still increased in treated cells at the highest concentration of vitamins. PMID- 1298662 TI - Safety aspects of food preservatives. AB - The use of food preservatives, such as benzoic acid, nitrites, and sulphites, as antimicrobials, and butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid and tocopherols, as antioxidants, has probably changed food production patterns and eating habits more than has the use of any other class of food additive. These food preservative chemicals confer substantial benefits on man, not only by the preservation and increased palatability of food, but also by affording protection against the pathological effects of reactive oxygen species (ROS) which are associated with cancer, cardiovascular disease and aging. Nevertheless, although most preservatives are now considered to be without potential adverse effects and are classified as GRAS, there have been problems concerning the safety of some of these chemicals, including the possibility of allergies from benzoic acid and sulphites, the formation of carcinogenic nitrosamines from nitrites, and the possible rodent carcinogenicity of BHA and BHT. The mechanisms of this toxicity at high dosage, the roles of the cytochromes P450, and the generation and scavenging of ROS in the toxicity of these chemicals, are reviewed and discussed. PMID- 1298663 TI - Toxicology of nitrates and nitrites. PMID- 1298664 TI - Toxicology of sulphiting agents. I: Animal studies. AB - Oral toxicity studies of sulphite in animals are briefly reviewed. On the basis of a chronic toxicity/carcinogenicity study of sodium metabisulphite in rats JECFA established an ADI of 0.7 mg SO2/kg using a safety factor of 100. The effects of sodium metabisulphite (1% Na2S2O5) on the composition of semi-purified rat diets during storage for at least three months have been studied. Under these conditions sulphite induced rancid off-flavours in diets containing unsaturated fats. The feeding of such stored sulphited-diets to rats resulted in growth retardation and diminished food efficiency. The extractability of the lipids from these diets was markedly reduced. Extraction with hexane, followed by ethanol extraction did not remove the toxic factor(s). It was suggested that sulphite in stored semi-purified diets may react with unsaturated fats leading to the formation of polymers of unsaturated fatty acids and/or other toxic substances. It is recommended that special attention is paid to the fatty acid composition of sulphited foods to be stored. PMID- 1298665 TI - Formaldehyde and hexamethylenetetramine as food additives: chemical interactions and toxicology. AB - Formaldehyde (FA) and hexamethylenetetramine (HMT) are used in cheese production to control gas-forming clostridia; FA also occurs naturally in some foods at levels of 1-20 mg/kg. The toxicology of FA and HMT are briefly discussed together with their reaction in foods. The most abundant end-product of FA in cheese is spinacine derived from the N-terminal histidine residue in gamma 2-casein. Acute and short term toxicological studies on spinacine enable a No Observed Effect Level of 300 mg/kg body weight/day to be determined, leading to an Acceptable Daily Intake (ADI) for man of 3 mg/kg body weight/day. From these data a Tolerance Level (TL) of 1800 mg spinacine/kg cheese can be derived, leading to a Safety Margin (SM) of 12.9. It is concluded that there is no appreciable health risk from consumption of cheese made using formaldehyde (Grana Padano) or hexamethylenetetramine (Provolone). PMID- 1298666 TI - The regulation of preservatives in the European Community. AB - Community regulation of preservatives is based on Council Directive 64/54/EEC of 5 November 1963, which defined 'preservatives' and established an exclusive approved list which Member States could permit. In some instances the Directive set limits on conditions of use and general purity criteria; specific purity criteria were established in a second Directive 65/66/EEC. The base Directive has been amended twenty-four times and that relating to purity criteria three times. The approved list has two parts, listing separately substances whose primary function is preservative and those whose primary function is other than preservative but which have a secondary preservative effect. Separate labelling laws require that the presence of additives, including preservatives, be declared. Permitted preservatives must be safe and technologically effective. Safety evaluation is carried out by the Scientific Committee for Food; technological effectiveness is assessed by experts from governments of Member States, food and chemical industry and the Commission. In future, preservatives will be encompassed by the general additives 'Framework Directive' which addresses areas including: exclusive permitted lists; lists of foodstuffs to which and conditions under which additives may be used; purity criteria; methods of analysis and sampling procedures. The Framework Directive also specifies criteria to be satisfied before an additive may be approved including guidance on what constitutes 'need', appropriate safety evaluation (and re-evaluation as necessary). Agreed conditions of use will need to ensure that ADIs are not compromised; where these are sufficiently high, the concept of 'quantum satis' might be applied whereas low ADIs may necessitate limitations on number of uses and levels of addition. PMID- 1298667 TI - Prepayment aggravations. PMID- 1298668 TI - An analysis of the ethics of health care providers with HIV. PMID- 1298669 TI - Growth of the dental laboratory industry. PMID- 1298670 TI - Ketorolac (Toradol) for dental pain. PMID- 1298671 TI - Clinical applications of synthetic bone in dentistry. Part 1. PMID- 1298672 TI - Changing dental requirements for glove selection and hand protection. PMID- 1298673 TI - Comparison of 3 automatic blood pressure screening devices. PMID- 1298674 TI - Use of porcelain for treating a maxillary central diastema. PMID- 1298675 TI - Radiographic techniques for presurgical assessment of dental implant sites. PMID- 1298676 TI - Recurrent aphthous ulcers: etiology and laser ablation. PMID- 1298677 TI - [Methodological problems of modern hygiene and aims of dividing the territory of Russia into medico-ecological regions]. PMID- 1298678 TI - [New law of the Russian Federation "On environmental protection" and tasks facing the hygienic science]. PMID- 1298679 TI - [ Hygienic nosologic diagnosis in modern medicine]. PMID- 1298680 TI - [Railway transport hygiene: conditions and problems]. PMID- 1298681 TI - [Hygienic rationale maximum allowable concentrations of 1,2,4-triazole in atmospheric air]. AB - Toxicological study of the 1,2,4-triazole determined the maximum one-time MAC of it in the ambient air at level of 0,1 mg/m3, average daily MAC of it - 0,05 mg/m3. PMID- 1298682 TI - [Dynamics of functional status indices of white rats exposed to the toxic effects of cobalt acetate]. PMID- 1298683 TI - [Comprehensive approach to assessment of the health status of Moscow children in districts with different levels of air pollution (methodologic, hygienic, clinical aspects)]. PMID- 1298684 TI - [Effect of ultra-violet irradiation and heavy metals on the survival rate of Escherichia coli in the water]. PMID- 1298685 TI - [Evaluation of the maximum allowable concentration of iron in the water]. AB - Experimental study of the iron allergenic effects on animals and pediatric examination of 130 schoolchildren in regions with high level of the iron in the water showed safety of the iron Mac in the water at the level of 0,3 mg/1. PMID- 1298686 TI - [Risk of halophilic morbidity in connection with the eutrophication of the seashore]. AB - Significant role of the littoral eutrophication in the growth of parahemolytic vibrio caused acute gastrointestinal disturbance- halophilosis was described. PMID- 1298687 TI - [Decrease of bacterial concentration in water as effected by microalgal biocenosis]. PMID- 1298688 TI - [Toxicological characterization of new nitrification inhibitors]. AB - Study of the two new nitrification inhibitors HMDI and TMDI showed a low toxicity. The lower toxicity with single intragastric administration was 485 mg/kg for HMDI, and 460 mg/kg for TMDI. PMID- 1298689 TI - [Study of morbidity connected with environmental pollution]. PMID- 1298690 TI - [Comparative oncogenicity of dust in the production of asbestos parts]. PMID- 1298691 TI - [Chronic effect of fluorides on the status of the pancreatic insular apparatus of workers]. AB - Decreasing of the insulin concentration and increasing of the C-peptide level in blood serum of 72 workers of cryolytes industries detected by radioimmunological method. These changes were caused by the fluorine intoxication of workers. PMID- 1298692 TI - [Influence of enzyme industry products on the human immune system]. AB - Enzyme industry products had significant allergo- and immunogenic effects on human body, manifesting by allergic dermatitis and respiratory forms of allergy. Most negative effects on immune system had alkaline protease 1 and 2, salizymelipase, neutral protease and protease C. Problems of diagnosis and modernizations of in-plant conditions were discussed. PMID- 1298693 TI - [Hygienic characteristics of the flour mill working environment]. AB - The fusariotoxins' content in the in-plant air of the flour mill and its effect on the workers' health status were investigated. PMID- 1298696 TI - [Food habits and work capacity indices of adolescents learning the specialties of locksmith and automobile mechanics]. AB - Complex assessment of the pupils studied the metalworker of motorcar repair service. Profession was given in aspect of their diet. Some recommendations based on the assessment were worked out. PMID- 1298695 TI - [Evaluation of physical development of preschool children in industrial cities]. PMID- 1298694 TI - [Influence of social factors on the health status of children in an industrial region]. PMID- 1298697 TI - [Hygienic assessment of non-traditional school furniture in schools providing general education]. PMID- 1298698 TI - [ Approaches to the radiation hygienic assessment of "soil components" of plutonium]. AB - By the Pathway-analysis the correlation coefficients between the plutonium isotopic contamination of soil and the human radiation dosage were defined. PMID- 1298699 TI - [Express-method for determining the level of 90 Sr in drinking water]. PMID- 1298700 TI - [Reaction of striated muscles to total vibration and noise]. PMID- 1298701 TI - [Methods of noise evaluation using a microcomputer]. PMID- 1298702 TI - [Effect of normal horse serum on chromium sensitization]. PMID- 1298703 TI - [Evaluation of mutagenic activity of some chemical combinations]. PMID- 1298704 TI - [Effect of hydrogen sulphide containing gas condensate on the humoral immune reaction]. PMID- 1298705 TI - [Changes in the monooxygenase system and lipid peroxidation components in liver microsomes as a measure of the effect of nitrogen dyes on the organism]. PMID- 1298706 TI - [ Methodologic aspects of the use of population morbidity and mortality indices in the development of health monitoring]. PMID- 1298707 TI - [Specifics of morphostructural skeletal changes as effected by thermo-oxidative products of polyethylene]. PMID- 1298708 TI - [Preparation of human placenta microvillous membrane and the study of its transferrin receptor]. AB - Human placenta microvillous membrane (PMM) was prepared by differential centrifugation and by sucrose gradient centrifugation, and the transferrin receptor (TfR) was studied using the receptor radioassay with 125I-transferrin as a radioligand. The factors affecting ligand-receptor binding reaction and the characteristics of TfR were also studied. The result showed that there was no significant differences (P > 0.1) in specific binding rates of 125I-transferrin to its receptor between the two membrane preparations, indicating that both of them could be used for TfR analysis, but the method of differential centrifugation was more simple and less time consuming. The study of TfR in sixty cases showed that the TfR binding sites on PMM and Bmax were 3.53 +/- 1.98 x 10(12) sites/mg membrane protein and 6.33 +/- 4.21 x 10(-12) mol/mg membrane protein, respectively. The Kd was 4.95 +/- 3.39 x 10(-9) mol/L, and the highest specific binding was 26% with nonspecific binding less than 3%. The conditions for ligand-receptor binding reaction were optimized when the concentrations of membrane protein and the 125I-transferrin in each test tube were 50 micrograms and 50,000 cpm (specific radioactivity being 2109 kBq/micrograms transferrin) respectively the incubation time was 30 min, and the concentration of polyethylene glycol added for separating B/F was 12% (W/V). transferrin binding to its receptor was characterized by high affinity, high specificity and being saturated. PMID- 1298709 TI - [Colony hybridization with digoxigenin labelled DNA probe]. AB - A simple, rapid method for colony hybridization has been developed. The DNA probes were labelled by digoxigenin. Hybridization signal was detected by enzyme linked immunoassay reaction. The results showed that this method is sensitive and reproducible, and it can be used for colony hybridization instead of isotopic methods. PMID- 1298710 TI - [Human blood stain identification using DNA amplification technique]. AB - DNA was extracted from human's and 15 different species of mammals' dried blood stains as well as from camel hair roots. DNA amplification was carried out using primers of Alu 9.1 and Alu 9.2. The results have indicated that this method can be used for the identification of human's dried blood stain under general condition. PMID- 1298711 TI - [The detection and analysis of leptospiral DNA in patients' serum of early leptospirosis by polymerase chain reaction and DNA hybridization with digoxigenin AMPPD]. AB - We have detected and analysed the leptospiral DNA in serum of patients with early Leptospirosis from the epidemic area of China by PCR and DNA hybridization with Digoxigenin (Dig)-3-(2'-Spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)- phenyl 1,2-dioxetane (AMPPD) to develop a sensitive, specific and reliable technique for the early diagnosis of leptospirosis, and full satisfactory results have obtained. Fourteen serum specimens from patients with leptospirosis proven by blood culture and serological test were prepared according to Boom's methods for PCR test, and oligonucleotide primers, named G1 G2, were obtained from a genomic library of leptospira interrogans. PCR amplification with serum specimens was performed. Each cycle of amplification consisted of denaturation at 94 degrees C for 1 min, annealing at 55 degrees C for 1 min and elongation at 72 degrees C for 2 min. Each sample was subjected to 32 cycles. The amplified DNA were separated by electrophoresis with 2% agarose gel and hybridized with the homologous DNA probe labelling with Dig-AMPPD by means of Southern blotting. All of 14 samples revealed the presence of leptospira and the strong signals were visualized with homologous DNA probe hybridization by Southern blotting. Negative and positive controls appeared correctly. The DNA fragment generated from PCR amplification homologically hybridized with the DNA of 16 strains which are from Yasudas' genomic species and represent the different genomic groups of leptospires. The single recognized band (about 400 bps) from 6 out of the 16 strains has come out which are representative of the principal strains in Sichuan, China.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298712 TI - [Detection of leptospiral DNA in the serum of 175 patients with early leptospirosis by polymerase chain reaction]. AB - We have developed a sensitive assay for leptospira, using the polymerase chain reaction (PCR). On the basis of the published nucleotides sequence of 23S rRNA gene from Leptospira interrogans serovar canicola strain Moulton, primers were chosen to produce an amplified fragment of 123 bp. Primer A: 5'GAT CTA ATT CGC TGT AGC AGG3' and primer B: 5'ACT TTC ACC CTC TAT GGT CGG3' Eight different svs. of Leptospira interrogans could all be detected by PCR, but the DNAs from L. biflexa. Leptonema bacteria, virus and human could not produce the specific amplified fragment. The assay detected approximately 10 fg of purified leptospiral DNA and 1 microliter serum of experimental animal. Positive results were obtained from simulated positive samples containing a single organism leptospiral DNA. The diagnostic test (proved by "gold standards": Clinical diagnosis; blood culture and MAT) showed that the sensitivity was 92.00%; the specificity 94.35%; the accuracy 92.54%; the positive predictive value 98.17%; the negative predictive value 78.13%; the positive likelihood ratio 16.25; and the negative likelihood ratio 0.0848. The diagnosis of early leptospirosis by using PCR may become a significant addition to diagnostic means. PMID- 1298713 TI - [Serum apolipoprotein E levels in 238 healthy adults and 161 hyperlipidemic subjects in Chengdu area]. AB - The serum apoE levels in 238 healthy adults in Chengdu are aware determined by radioimmunodiffusion (RID) assay. The average apoE level was 3.98 +/- 0.98 mg/dl (chi +/- s). The result was basically identical with other reports. There is no difference in sex, and the level has a tendency to increase with age. One hundred and sixty-one hyperlipidemic subjects (including types IIa, IIb, IV and V were compared with the normals. Their serum apoE levels increased by different percentages depending on the type of hyperlipidemia. The percentage of increasing was especially higher in types V and IIb. The content of apoE in serum positively correlated with serum triglyceride (r = 0.65, P < 0.01) and with serum total cholesterol (r = 0.50, P < 0.01). PMID- 1298714 TI - [Preparation of antigen and antibody against aflatoxin B1]. AB - Carboxymethyloxime of aflatoxin B1 (AFB1) was synthesized by refluxing AF B1 with carboxymethoxylamine hemihydrochloride for 4 hours in the presence of pyridine. AF B1-BSA (antigen) was made successfully by coupling AF B1-oxime with bovine serum albumin (BSA) in the presence of a water soluble carbodiimide. The rabbits were immunized with the artificial immunogen which had been purified by dialysis. The titers of antisera were determined by indirect enzyme-linked immunosorbent assay (ELISA) which was developed by ourselves. The highest titer was 1:100,000. PMID- 1298715 TI - [Establishment and preliminary application of competitive ELISA using monoclonal antibody against Trichinella spiralis]. AB - Monoclonal antibody competitive ELISA was devised with a highly specific McAb (2G8) against T. spiralis. Among 20 rabbits infected with T. spiralis experimentally. 35% (7/20) were positive on the 17th day post infection (PI); 100% positive on the 31st day PI. No cross reaction was found with 29 sera of rabbits infected with other kinds of helminth. The dynamic antibody titer of five infected rabbits sera were studied with this method. The change may be helpful to judge the state of infection. In short, anti-T. spiralis McAb competitive ELISA can be regarded as a sensitive and specific immunological diagnostic method for T. spiralis infection. PMID- 1298716 TI - [Changes in glomerular polyanions and ultrastructure induced by protamine in rats]. AB - Perfusion of rat kidneys with polycation protamine, resulted in pathologic alterations of glomeruli very similar to those observed in minimal change nephrotic syndrome in human. In the experimental model, colloidal iron stained kidney tissue sections were analyzed quantitatively by image analyzer and stereology in combination with the observation of other glomerular ultrastructure. The mean thickness of foot processes and the foot processes making up the volume fraction of glomerular capillary were determined. The studies showed that there was a significant decrease in glomerular polyanions of kidneys perfused with protamine as compared with that of the control group (P < 0.01). The glomerular alterations included swelling and fusion of foot processes and narrowing or loss of filtration slits. Electron-dense particles formed by binding of protamine to polyanions were seen primarily in the lamina rara externa of glomerular basement membrane and also along the lamina rara interna and on the foot process surface, which showed the distribution feature of glomerular filter. These results suggest that the ultrastructure alterations of glomeruli may result from the neutralization of polyanions by perfusion with protamine. PMID- 1298717 TI - [Prognostic significance of nuclear DNA measurement with flow cytometry for laryngeal squamous cell carcinomas]. AB - DNA ploidy, S% and proliferative index (PI) of carcinomatous cell were evaluated with FCM in 41 patients with laryngeal primary squamous cell carcinomas which were operated on in our department during the period between Jan. 1979 to Oct. 1987. The results showed that DNA aneuploidy was identified in 65.85% of the cases (27/41) and patients with aneuploid carcinomas had higher S% (mean +/- standard: 23.22 +/- 9.57%), higher PI (mean +/- standard: 37.59 +/- 9.57%) and higher rate of relapse and/or metastasis than those with diploid tumours (55.55% vs 11.77%, P < 0.025). Patients with aneuploid carcinomas also correlated with an unfavorable prognosis compared with those with diploid tumors. Cases with aneuploid and diploid carcinomas had 66.11% and 92.86% respectively for two years postoperation survival rate; 46.74% and 92.86% respectively for five years postoperation survival rate (Log-rank test: chi 2 = 5.96, P < 0.025). We conclude that nuclear DNA measurement with flow cytometry is of important significance in estimating prognosis and guiding treatment for laryngeal squamous cell carcinomas. PMID- 1298718 TI - [Studies of outer membrane protein profiles by SDS-PAGE for Campylobacter jejuni in an epidemiological investigation]. AB - The characteristics of outer membrane protein profiles of 41 strains of Campylobacter jejuni from various sources by SDS-PAGE was studied. Seven and nine OMP patterns were differentiated respectively by the presence or absence of six outer membrane protein bands and by the number and size of the molecular weight of the major protein bands. Comparing the OMP patterns of the strains from human with those from animals, the authors inferred that chickens and other animals might be one of the sources for the human infection of Campylobacter jejuni in this district. A comparison between the OMP patterns of the strains from diarrheic children and those from healthy carriers suggested that the pathogenesis of Campylobacter jejuni be possibly associated with the outer membrane proteins. Using the techniques, the authors studied the infection of Campylobacter jejuni in a nursery. The result showed the infection was sporadic and of multi-sources, as evidenced by the multi-patterns of the outer membrane protein profiles. It also indicates that the person-to-person transmission plays a significant role in the infection of Campylobacter jejuni. PMID- 1298719 TI - [Effects of zinc deficiency and vitamin D deficiency on bone calcification and development of rats]. AB - Zinc deficiency rat model was made by feeding zinc deficiency diet. The level of bone calcium of the zinc deficiency rats was significantly lower than that of the control rats. Their bone cortex was thinner and bone density decreased. The counts of their cartilage cells and hypertrophic cells of epiphyseal plate were less frequent, and the diameter of their hypertrophic cells was smaller than that of the controls. It suggested that zinc deficiency caused defective bone calcification which was similar to that in vitamin D deficiency. Zinc deficiency seemed to hinder the linear growth of long bone and might be the cause of dwarf. PMID- 1298721 TI - [Relation between the occurrence of malignant arrhythmia during acute myocardial ischemia and the weight of ischemic myocardium in goats]. AB - The coronary collateral circulation of goat is very spare, so myocardiac ischemia model of goat can simulate the patient previously with normal coronary circulation and suddenly developing complete occlusion of coronary arteries. In this study 80 Chengdu goats were used, and the branches of their left coronary artery were ligated. Ventricular tachycardia (VT) developed in 23 goats and ventricular fibrillation (VF) in 39 goats. VT and VF both occurred in the early phase of acute myocardial ischemia, and both had 6 min as the median time of onset. In 71 cases data on the weight of myocardiac ischemic area were collected, in which the weight percentage of ischemic area relating to the ventricles of 34 goats with VF was significantly higher than that of 37 goats without VF (35.4 +/- 2.4% vs 19.5 +/- 1.9%). After coronary ligation, 9 cases directly precipitated into VF which could not be defibrillated. In the remaining 62 cases, the weight percentage of ischemic area of 21 cases with VT was higher than that of 41 cases without VT (32.9 +/- 2.8% vs 20.9 +/- 2.1%). The relationships between the incidence of VT or VF and the weight percentage of ischemic area were fitted with logistic curve. The likelihood of occurrence of VT or VF is increased as the weight percentage of ischemia area goes up. PMID- 1298720 TI - [Mutagenesis study of ethylmethane sulfonate with shuttle vector plasmid pZ189]. AB - Shuttle vector plasmid pZ189 was used as a molecular tool and the SupF inserted in the plasmid was worked as a target gene for mutagenesis study. The host cells (E. coli MBM 7070) with pZ189 were treated with ethylmethane sulfonate (EMS) and plated on the selective media containing X-gal (5-bromo-4-chloro-3-indolyl-beta-D galactoside) and IPTG (isopropyl-beta-D-thiogalactoside). The SupF and the LacZ amber mutant carried by the host cells complemented each other and thus made the colonies blue on the selective media. However the colonies derived from the SupF mutants changed the colour from blue to white. The mutant frequencies in a series of experiments with different concentrations of EMS were estimated. Furthermore, the DNA isolated from 5 SupF mutants was digested with restruiction enzyme Hha I. It suggests that the 214 bp Hha I fragments containing mutant SupF could be distinguished from their wild type counterparts by temperature-gradient gel electrophoresis under optimal conditions. PMID- 1298722 TI - [Effects of adrenergic agonist on population spike in CA1 region of hippocampal slices from partial and full kindled rats]. AB - Effects of adrenergic agonist on population spike (PS) amplitude were studied extracellularly at CA1 region of hippocampal slices from partial and full kindled rats with coriaria lactone (1-1.25 mg/kg, two days a time, i.m.) and compared with those from control rats. 5 mumol/L norepinephrine (NE) increased PS; 50 mumol/L NE decreased it slightly. 5 mumol/L isoproterenol (ISO) increased PS. 100 mumol/L phenylephrine (PE) decreased it. The effects of increasing and decreasing PS could be antagonised by beta and alpha adrenergic antagonists, respectively. The effects of NE and PE on PS amplitude showed no significant difference between the control and kindled rats. The effect of beta-adrenergic agonist ISO on PS amplitude in hippocampal slices from partial kindled rats was less than that of control (P < 0.01). The effect of ISO on PS of full kindled rats was partially recovered. PMID- 1298723 TI - [Effects of calcium channel blocker verapamil on hippocampal kindled seizures induced by coriaria lactone in rabbits]. AB - Eighteen fully kindled rabbits, whose epilepsy had been produced by intrahippocampal (i.h.) injections of 2 microliters of diluted solution containing 0.32 or 0.55 micrograms of coriaria lactone (CL), were separated into three groups. One of them was used as the control group. For seizure, all animals were given CL (0.6-1 micrograms/2 microliter i.h.). Ten minutes later, the verapamil (VR) group of six rabbits was treated with VR (1.5 or 2 mg/kg i.m. 2.5 or 5 micrograms/2 microliters i.h.); the normal saline (NS) group (six rabbits) received 0.8 ml/kg (i.m., in the same volume as that of the VR 2 mg/kg injection) or 2 microliters (i.h.) of NS; the control group of six received neither VR nor NS. The experiments were made once every eight days. Hippocampal EEGs of all animals were recorded by telemetric method and their behavior after injection was observed continuously in 4-7 hours. The results of the experiment indicated that the i.h. administration of 2.5 or 5 micrograms/2 microliters of VR is effective on hippocampal kindled seizures induced by CL in rabbits, but the curative effects of the i.m. administration of 1.5 or 2 mg/kg of VR were less notable than those of the i.h. administration. PMID- 1298724 TI - [Age-related morphological changes in the suprachiasmatic nucleus of the rat hypothalamus]. AB - A comparative ultrastructural investigation of the hypothalamic suprachiasmatic nuclei (SCN) of young, adult and senescent SD male rats was carried out. The neurons and neuroglial cells in SCN of the senile rats displayed more lipofuscin (Lipo) accumulation in comparison with those of the younger animals. Golgi apparatus (Gol) of the three age groups converted from well-ordered cisternae to irregular ones with extensive dilatation and vacuolization. More neuroglial cells with broader somatic membrane appositional to that of neuron participated in satellitosis in the senile age group. Some unusual structures such as special arrangements of the rough endoplasmic reticula and multilamellar neuroglial envelope (Mge) wrapping neurite were encountered in the perikarya of some neurons or SCN neuropile respectively. PMID- 1298725 TI - [A computer program for the power spectra analysis of biomedical signals]. AB - This paper presents a useful program for the power spectra analysis of biomedical signals on a microcomputer. The frequency spectra to show the allocation of frequency were calculated from the acquired biomedical signal via a window algorithm and the real signal special handling. The frequency spectra became normalized power spectra through algorithm and could be displayed on a monitor or printer in the mode of histogram. We have got good results using this program to compute the power spectra of phrenic nerve discharges from the rabbit. PMID- 1298726 TI - [High performance liquid chromatographic determination of hydroxyphenytoin in human urine]. AB - A high-performance liquid chromatographic method for the determination of p hydroxyphenytoin (p-HDPH) in human urine was reported. Following acid hydrolysis of urine sample at 90 degrees C for 1 h, an internal standard, nitrophenol, was added. The sample was extracted with n-hexane-ethyl acetate (50:50), and organic layer was evaporated. The residue was dissolved in methanol and chromatographed on an Ultrasphere-ODS column, using a mobile phase of phosphate buffer (0.03 mol/L, pH 6.0): methanol (65:35) at a flow rate of 0.8 ml/min. The eluent was monitored at 240 nm. The standard curve was linear within the range 5.0-200 micrograms/ml (r = 0.9998). Analytical recovery rates were 102.8 +/- 7.3% (p-HDPH 9.70 micrograms/ml, n = 5) and 104.9 +/- 6.4% (p-HDPH 54.70 micrograms/ml, n = 5). The cumulative recovery of p-HDPH in 0-12 h volunteers' urine samples accounted for 20% of the oral dose of 100 mg phenytoin sodium. PMID- 1298727 TI - [A method for acquiring newborn larvae of Trichinella spiralis in vitro]. AB - This paper reports a simple method for acquiring numerous newborn larvae of Trichinella spiralis in vitro. Adults of T. spiralis, collected from small intestine on rats which were infected with infective larvae separated from mice infected experimentally, were put into tissue culture bottle containing M199. Then the bottles were incubated in CO2 incubator (37 degrees C, 5% CO2) for 15 20h. The newborn larvae were collected by passing through filtration, centrifugation and repeated wash. The results showed that this method is effective in terms of the activity of the adults and newborn larvae and the amount of larvae gained. The method in economical and can control bacterial contamination to a certain extent and extract ES antigen of adults and newborn larvae from the culture solution. PMID- 1298728 TI - [Simultaneous analysis of vitamin B complex by least square UV spectrophotometry]. AB - Simultaneous analysis of VitB1, VitB2 and VitB3 in Vitamin B Complex tablets was made by least square UV-spectrophotometry. The results showed that the contents of VitB1, VitB2 and VitB3 could be calculated by computer with least square method using 12 absorbances of 239, 241, 257, 259, 261, 263, 266, 269, 270, 279 and 281 nm wavelengths. The reclamation of VitB1 was 101.4% (CV% = 0.88, n = 3), of VitB2 98.5% (CV = 0.43, n = 3), and of VitB3 101.3% (CV% = 0.15, n = 3). PMID- 1298729 TI - [A study on the relationship between pathologic morphology and clinical prognosis of renal cell carcinoma]. AB - One hundred and six cases of renal cell carcinoma (RCC) were studied with an objective to investigate the effects of clinical stages, histological patterns (grading), cell types, nuclear grading and tumor sizes on the postoperative survival time of the patients. The results showed that there were no statistical differences in the postoperative survival time among different histological patterns and among different cellular types, such as clear cell, granular cell and mixed cell. But those with either diffuse sarcomatoid pattern or undifferentiated cell type had poor prognosis. The patients with tumor size greater than 10 cm in diameter had poor prognosis. The prognosis-deciding factors for RCC patients were the clinical staging and nuclear grading. We suggest that the nuclear grading of RCC be noted in every pathological report, so as to provide reference for clinical evaluation of the prognosis and further treatment. PMID- 1298730 TI - [Pathological study on epithelioid sarcoma]. AB - Thirteen cases of epithelioid sarcoma were studied by light microscopy (LM), electron microscopy and immunohistochemical technique. LM revealed a nodular pattern of the tumor cells, which consisted of various degrees of a typical epithelioid cells and plump spindle-shaped cells. Irregular necrosis was seen in the centre of some nodules. Ultrastructurally the tumor cells exhibited abundant intermediate filaments, desmosome-like cell junctions and small intercellular spaces surrounded by microvilli. Immunohistochemically, there was positivity for vimentin and keratin. The author discussed diagnosis, differential diagnosis and histogenesis of epithelioid sarcoma. PMID- 1298731 TI - [Pulmonary function disturbances in patients with hepatic cirrhosis]. AB - The results of five pulmonary function tests on 52 patients with uncompensated hepatic cirrhosis were presented. Compared with matched healthy adults, the patients had decreased values of VC, TLC and DLCO, and their RV/TLC increased (P < 0.05-0.001). Possible pathogenic factors were investigated. The ascites showed evident influences on pulmonary function. In addition to the disorders detected by the above 4 tests, FRC decreased in the patients with ascites. A comparison between the patients with albumin below 30g/L and the patients with albumin above 30g/L revealed that reduced plasma albumin also played role in decreasing VC, TLC and DLCO. Besides the effects of ascites, severe varices of esophagus should have relation to the increase of RV/TLC and the decrease of DLCO. PMID- 1298732 TI - Inferior alveolar nerve transposition in combination with Branemark implant treatment. AB - The surgical protocol for inferior alveolar nerve transposition together with the Branemark implant treatment is described. The short-term follow-up results of the first ten procedures are presented and show an initial 2- to 3-week duration of anesthesia. In all regions treated, signs of paresthesia/hypoesthesia have been registered for 1 to 7 months. After 6 months, seven of the regions recovered completely with regard to nerve sensation. PMID- 1298733 TI - Periodontal regenerative therapy with coverage of previously restored root surfaces: case reports. AB - Two case reports are presented to demonstrate a treatment that restores proper esthetics, cures hypersensitivity, and enhances periodontal support for cases of root caries or failing Class V restorations associated with gingival recessions. The procedure involves removing the existing restoration, elevating a trapezium shaped full thickness flap, root planing to achieve a desired concave shape, and placing a barrier membrane. In both cases, satisfying clinical results have been maintained for 18 months. PMID- 1298734 TI - Jawbone enlargement using immediate implant placement associated with a split crest technique and guided tissue regeneration. AB - Five patients with sufficient vertical bone height but insufficient bone width for implant placement were chosen for treatment with a split-crest technique combined with guided tissue regeneration. The surgical technique involved splitting the alveolar ridge longitudinally in two parts, provoking a greenstick fracture. A chisel was then used to make a fine cut and spread apart the two cortical plates. Implants were then placed. Implants and defects were covered with expanded polytetrafluoroethylene membranes. Biometrical examination showed a gain in bone width, varying between 1 and 4 mm; maxillary sites showed greater ridge enlargement. Histologic examination showed regeneration of bone tissue between the two portions of the split crest. This membrane technique could be effective and predictable for horizontal ridge augmentation associated with immediate implant placement. PMID- 1298735 TI - Clinical results and guidelines on Steri-Oss endosseous implants. AB - A statistical study of the Steri-Oss implant system, concerning 673 implants placed in 280 patients in the course of a 5-year period, allows a therapeutic proposal to be made that will optimize the success rate of osseointegration. The study revealed indications specific to each type of implant, according to the depth and density of available bone. The use of titanium screws is recommended whenever bone quality is type I. In all other cases, where the density of bone decreases and approaches type IV, especially in the posterior maxilla, cylindrical hydroxyapatite-coated implants are recommended. PMID- 1298736 TI - Achieving ideal esthetics in osseointegrated prostheses. Part II. The single unit. AB - There are several advantages to the CeraOne single-tooth abutment. It seats directly onto the fixture, forming a nonrotating joint. A new type of gold alloy screw that can be tightened to 32 N/cm is used. In addition, the restoration is constructed on a prefabricated ceramic cap onto which porcelain is directly baked. A case report illustrates the technique and the highly esthetic results of such single-tooth replacement. PMID- 1298737 TI - Evaluation of an in vitro invasion assay for use on solid tissue samples and cultured cells. AB - An invasion assay, developed for monitoring the in vitro penetration of reconstituted basement membrane, matrigel, was modified and successfully applied to solid tumours, normal tissues as well as a variety of normal and tumour cell lines. However, we found that some normal fibroblasts were capable of in vitro invasion whilst some malignant cell lines with invasive capacity in vivo did not penetrate the matrigel. Nevertheless, this method can distinguish invasive capacity within a tumour model, and as a consequence may be used to elucidate some of the biochemical mechanisms in the invasion process comparing cells grown both in vitro and in vivo. Since the method does not always correlate with invasion in vivo the results must be interpreted with caution. PMID- 1298738 TI - Activation of protein kinase A increases the in vitro invasion, migration, and adherence to reconstituted basement membrane by Lewis lung carcinoma tumor cells. AB - Prostaglandin E2 (PGE2) stimulated in vitro invasion, migration, and adherence to reconstituted basement membrane by metastatic Lewis lung carcinoma (LLC) clones, but this stimulation was blocked by protein kinase A (PKA) inhibitors and by expression of a transfected mutant RI alpha which blocks PKA activation. In vitro migration and adherence of metastatic LLC transfectants was heightened by expression of a transfected C alpha gene and further heightened by Zn2+ induction of the expression vector. Nonmetastatic LLC were not migratory nor invasive. However, nonmetastatic LLC that were stably transfected with a C alpha gene were both migratory and invasive, particularly when C alpha expression was further induced with Zn2+. The results of these in vitro studies show that PKA can enhance the metastatic characteristics of LLC. PMID- 1298739 TI - Preferential growth stimulation of metastatic rat mammary adenocarcinoma cells by organ-derived syngeneic fibroblasts in vitro. AB - To determine whether organ-derived fibroblasts differentially affect the growth of cells from tumors that preferentially metastasize to specific organs, we investigated the effect of medium conditioned with primary cultured rat fibroblasts from various organs on the in vitro growth of metastatic cell lines and clones of the rat 13762NF mammary adenocarcinoma. The conditioned medium from fibroblasts derived from rat mammary fat pad differentially stimulated tumor cell growth in monolayer culture and clonogenic growth in soft agarose of the highly metastatic clone MTLn3 in a dose-dependent manner. Conditioned medium from fibroblasts derived from the lung and liver also stimulated the growth of clone MTLn3 cells but to a lesser extent than did mammary fat pad fibroblasts. In contrast, poorly metastatic cell clones (MTC, MTPa) did not respond to the growth stimulatory factor(s) from the fibroblast-conditioned medium. The factor(s) responsible for the growth stimulation were inactivated by heat and trypsin treatment and inhibited by low pH and cycloheximide. The result suggest that fibroblasts in different organs have different effects on tumor cell growth, and they may determine, in part, the organ specificity of tumor development and metastasis. PMID- 1298740 TI - Fibronectin degradation by human gastric carcinoma cell lines and its associated proteases in relation to stromal invasion in nude mice. AB - The invasiveness of human gastric carcinoma cell lines (MKN45 and MKN28) in the subcutaneous tissue of nude mice and the degrading capacities of extracellular matrix (ECM) were studied. MKN45 cells were more invasive than were the MKN28 cells. Immunostaining revealed dense lamellar accumulation of fibronectin (FN) around the tumors. Along the front of the invasive MKN45 growth, however, the FN fibers were discontinuous and/or had completely vanished; the MKN28 tumor showed no FN fiber disconnection. ECM components other than FN never displayed such peritumoral massive accumulation. Cocultivation of human fibroblasts with MKN45 cells, more evidently than with MKN28 cells, revealed degradation of FN produced by fibroblasts in contact with each tumor. Both cell lines produced several FN degrading enzymes in serum-free cultures. Proteases from the MKN45 medium were more active than were those of MKN28 in urokinase-type plasminogen activator (uPA) and metal-dependent serine proteinase-like proteases of 75 and 68 kDa in molecular weight (MW). Type I collagen-degrading 48-kDa protease was also detected from MKN45 medium but not from the MKN28 medium. MKN28 cells secreted other kinds of FN-degrading enzymes, estimated at approximate MWs of 29 and 100 150 kDa. We found no distinct differences in capacity to produce ECM components or ability to adhere to purified ECM components between these two cell lines. From these results we conclude that the stromal invasion of these cells into the subcutaneous tissue of nude mice is profoundly related to their FN-degrading capability. This capability may be catalyzed by uPA and/or metal-dependent serine proteinase-like proteases of 75 and 68 kDa. PMID- 1298741 TI - Differential expression of the H-2Dk MHC class-I antigen and tissue inhibitor of metalloproteinases in metastatic and nonmetastatic T-10 fibrosarcoma cells. AB - In previous studies, we have demonstrated that the highly metastatic IE-7 cell clone, derived from the T-10 fibrosarcoma, expressed both the H-2Dk and H-2Db genes, whereas a nonmetastatic IC-9 clone, derived from the same tumor, expressed only H-2Db, suggesting that the H-2Dk product might be involved in the metastatic phenotype. To substantiate this notion, IC-9 cells were transfected with an H-2Dk expressing vector. Although all of the 4 randomly selected transfectant subclones elicited high H-2Dk expression, only one was as metastatic as IE-7 cells. This metastatic transfectant resembled IE-7 cells also in its inability to evoke CTL response in syngeneic mice, whereas the other transfectants were quite competent in this respect. It thus appears that the H-2Dk product may contribute to the metastatic phenotype provided that it is immunogenically abnormal. In addition, the present study provides evidence to suggest that lack of production of the tissue inhibitor of metalloproteinases TIMP-1/TIMP-2 is another important determinant in the metastatic phenotype of these cells. PMID- 1298744 TI - Current concepts in endodontic surgery. PMID- 1298743 TI - Periodontal screening and recording. PMID- 1298742 TI - Antimetastatic activity of boro-amino acid analog protease inhibitors against B16BL6 melanoma in vivo. AB - Di- and tripeptide boro-amino acid analog protease inhibitors with specificity for chymotrypsin and elastase decrease the number of melanotic foci formed in the lungs of mice in the B16BL6 experimental metastatic tumor model. These effects were at significantly lower concentration than leupeptin or other natural chymotrypsin inhibitors previously reported. These results support the involvement of elastase and chymotrypsin in the metastatic process. PMID- 1298745 TI - Controlled tooth eruption for restoration of a local gingival defect. PMID- 1298746 TI - Reliability of measurements from photocopies of study models. PMID- 1298747 TI - Orthodontic office design. Staff amenities. PMID- 1298748 TI - Rapid Class II molar correction with an open-coil jig. PMID- 1298749 TI - Improving your case acceptance rate. PMID- 1298750 TI - Comprehensive assessment of anteroposterior jaw relationships. PMID- 1298751 TI - The pendulum appliance for Class II non-compliance therapy. PMID- 1298752 TI - The effect of adhesive-layer thickness on bond strength. PMID- 1298753 TI - A new instrument for functional appliance bite registration. PMID- 1298754 TI - A method for determining headgear force systems. PMID- 1298755 TI - An office video communication system. PMID- 1298756 TI - Management and marketing. Getting started. PMID- 1298757 TI - A versatile utility arch. PMID- 1298758 TI - A cross-sectional and longitudinal study of craniomandibular dysfunction in an elderly population. AB - Three cohorts of subjects in their 70s (born in 1901 to 1902, 1906 to 1907, and 1911 to 1912; n = 1,065) were investigated by means of questionnaires and clinical examination. The first cohort was followed to age 83 and the others to age 75. Symptoms of craniomandibular dysfunction were reported less frequently with increasing age. This was especially marked in men. Clinical signs of severe dysfunction were rare, and according to the Helkimo classification they tended to decrease with increasing age. The longitudinal results mainly confirmed the cross sectional data. The results indicated that there is no increased risk of craniomandibular dysfunction with aging. On the contrary, awareness of such symptoms tended to decrease with aging. PMID- 1298759 TI - Signs and symptoms of craniomandibular disorders in men with Reiter's disease. AB - Fifty-two consecutive male patients with a medical diagnosis of Reiter's disease (RD) and 52 individually matched controls with no known general joint disease were examined for subjective symptoms and clinical signs of craniomandibular disorders (CMD) using routine stomatognathic methods. Patients with RD had more frequent and more severe subjective symptoms than did controls (P < .05). According to Helkimo's Clinical Dysfunction Index, subjects in the RD group had more severe clinical signs than those in the control group (P < .05). The most characteristic sign or symptom of CMD in the RD group was pain in the TMJ during function. PMID- 1298760 TI - Prevalence of structural bony change in the mandibular condyle. AB - Estimated on data derived from a longitudinal study of 172 orthodontic subjects, structural bony change in the mandibular condyle occurs in 5% of the individuals documented from childhood to adulthood. The first appearance generally was between 12 and 16 years of age. Differential diagnosis based upon signs and symptoms of CMD registered simultaneously, as proposed in the 1990 guidelines for craniomandibular disorders appeared to be inconsistent. To illustrate how suddenly the process of bony change may proceed, a case report is presented in which a severe change transpired within a 1-year interval in a 13-year-old patient. PMID- 1298762 TI - Evaluation of masticatory function before and after treatment in patients with craniomandibular disorders. AB - The masticatory function was evaluated in 12 patients with signs and symptoms of craniomandibular disorders of mainly muscular origin. Palpation of the masticatory muscles and measurements of occlusal force endurance, on a submaximal level with visual feedback, and of masticatory efficiency were performed before and after treatment. Significant changes occurred between the two measurements. Of a total of 10 masticatory muscles, 8 were sensitive to palpation before treatment and 2 after treatment. Occlusal force endurance increased from 92.5 seconds before treatment to 132 seconds after treatment, and masticatory efficiency increased from 54% to 65%, respectively. It is concluded that the masticatory muscle function of these patients is compromised and that treatment had a positive effect on the masticatory function. PMID- 1298761 TI - Atypical odontalgia. AB - Atypical odontalgia describes atypical facial pain in apparently normal teeth. Unfortunately, dentists usually consider this diagnosis only after the failure of invasive treatment. Atypical odontalgia patients are typified by women in their mid-40s who complain of persistent pain in one or more premolar or molar teeth. They associate pain with dental procedures or trauma to the region. While the cause of atypical odontalgia is uncertain, deafferentation pain appears to be a plausible mechanism. This article reviews relevant aspects of this perplexing pain problem. To help avert the untimely diagnosis of atypical odontalgia, identifying inclusion criteria are presented. PMID- 1298763 TI - A laboratory assessment of recording reliability and analysis of the K6 Diagnostic System. AB - This laboratory study investigated the recording reliability and analysis of the K6 Diagnostic System, a computerized instrument that records mandibular movements in three planes. Two special devices were utilized for this purpose, one commercially available and the other designed and constructed by the authors. These devices could produce linear movements and simulate head and mandibular movements, respectively. The largest distortion of the simulated mandibular movements was found in the frontal plane tracings of simulated chewing patterns. For the linear movements in an x-axis, the error of the analyzed K6 system ranged from 9.4% to 30% and in a z-axis from 0% to 15%. A considerable degree of head movement was required to produce a significant error on the K6 measurements. PMID- 1298764 TI - Radiographic signs of temporomandibular disorders to predict outcome of treatment. AB - In 32 consecutive patients with temporomandibular disorders radiographic changes were correlated with the patients' assessment of treatment outcome. The patients had been referred for tomographic examination because the clinical signs and anamnestic data were inadequate for definite clinical diagnosis. Initially all patients were treated conservatively with a flat occlusal splint. Surgery was advised in appropriate cases. The subjective effect of treatment was assessed using a questionnaire, and the material was divided into responder and nonresponder groups. Seventy-eight percent (25) of the patients experienced a positive subjective response to the treatment. No radiographic sign was found to be statistically correlated to the outcome of treatment. PMID- 1298765 TI - Effect of an anesthetic injected into the temporomandibular joint space in patients with TMD. AB - Twenty-three adult female patients were studied before and after injection of one temporomandibular joint to relieve pain. These patients had exhibited a persistent history of pain within their mandibular, neck, and somatic muscles, despite repeated treatment involving occlusal splints, physical therapy, and biofeedback. Patients were also screened for possible condylar degeneration using corrected tomograms. Initially, patients rated their pain on a linear scale from 0 to 10 and designated the site of the pain on a full-body-profile chart. The presence and location of the pain was determined by manual palpation using a rating scale of 0 to 10, and by the patients designating those regions perceived as painful by marking a full-body-profile chart. After this initial screening, subjects received an injection of 1% lidocaine (1:100,000) to the upper intracapsular space of one joint. The pain profile chart was completed by the patients 15 minutes after injection. Twenty of the 23 patients demonstrated a significant decrease in pain located in facial, head, and neck regions. These data suggest that injection of a local anesthetic to the temporomandibular joint will decrease pain for a short time in ipsilateral and contralateral regions of the head and neck. PMID- 1298766 TI - Chronic hemifacial pain caused by a tortuous facial artery: report of a case. AB - An adult white female presented with a 22-year history of pain on the right side of her jaw. Digital palpation over the facial artery at the inferior border of the mandible elicited and exacerbated the pain. Surgical exploration revealed a coiled, tortuous facial artery. Removal of the aberrant artery provided complete pain relief. PMID- 1298767 TI - Research diagnostic criteria for temporomandibular disorders: review, criteria, examinations and specifications, critique. PMID- 1298768 TI - [Band keratopathy. Symptomatological value based on 23 cases]. AB - This study attempts to better define band keratopathy. A total of 23 eyes were reviewed, the largest sample ever published. The histopathology of this condition, characterized by lesions situated beneath the corneal epithelium, as well as its various clinical forms, are described. A distinction is drawn between band keratopathy and brown band keratopathy from an etiological and histological standpoint. The various available treatments are reviewed, emphasising lamellar keratoplasty as the safest and most effective technique. PMID- 1298769 TI - [Surgery of retinal detachment of patients with pseudophakia using the panfunduscope]. AB - Examination of the extreme periphery of the fundus of patients with pseudophakic retinal detachment is difficult due to poor pupil dilatation, optical aberrations from the intraocular lens, opacification of the posterior capsule or peripheral capsular remnants. Fifty-one patients with pseudophakic retinal detachment were operated on with using the wide angle panfunduscope of Rodenstock. It allows a very satisfactory pre- or intraoperative view of the extreme periphery of the fundus using the slit-lamp of the operative microscope combined with a scleral indentation. In only 3 cases no break was found in spite of pre- and intraoperative examination of the fundus periphery with the panfunduscope. Anatomic success was achieved in 47 out of 48 patients with a minimum of 6 months of follow-up; 3 patients were lost to follow-up. The mean postoperative visual acuity was 0.5. Unlike other methods of fundus examination, such the 3 mirror Goldmann lens or the indirect binocular ophthalmoscope, the panfunduscope allows good visualization of the peripheral retina of patients with pseudophakic retinal detachment using the slit-lamp of the operative microscope combined with a scleral indentation. Thus, small peripheral retinal breaks, often associated with pseudophakic retinal detachment, can be identified. PMID- 1298770 TI - [Association of progressive external ophthalmoplegia and lattice corneal dystrophy]. AB - The authors conducted a study in a family pedigree comprising 33 patients (men 16, women 17). In this pedigree there coexisted patients with progressive external ophthalmoplegia and corneal lattice dystrophy. Two patients with progressive external ophthalmoplegia and ten with lattice corneal dystrophy were found. One of our patients (propositus) suffered from both diseases. Our study proves that, in this pedigree, progressive external ophthalmoplegia and corneal lattice dystrophy have an autosomal dominant mode of inheritance. PMID- 1298771 TI - [Post-varicella disciform keratitis]. AB - Varicella disciform stromal keratitis is rare. It occurs several weeks or months after the skin rash. We report 4 cases in children, two of whom developed one or more recurrent episodes. Treatment based on local steroids was long and difficult to dose. One case treated with oral aciclovir did not show a better clinical course than the other patients. PMID- 1298773 TI - [Orbital invasiveness of Merkel cell tumor of the eyelid]. AB - A new case of neuroendocrine carcinoma (Merkel cell tumor) of the eyelid is reported. Local recurrence, spread to the orbit, led to exenteration and death of the patient. This trabecular carcinoma can be identified by histology, immuno histochemistry and electron structural microscopy. PMID- 1298772 TI - [C2F6 in the treatment of retinal detachment associated to PVR: therapeutic trial]. AB - We conducted a clinical trial on C2F6 as a retinal tamponade in the management of retinal detachment with proliferative vitreoretinopathy. Twenty seven eyes of 27 consecutive patients were enrolled in the study. Permanent retinal reattachment was achieved in 21 eyes (78%). The anatomic success rate was 85% in eyes with grade B PVR (17/20 eyes), and 57% in eyes with grade C and D PVR (4/7 eyes). The success rate was as high as that achieved in a previous series of eyes managed with the use of C3F8 combined with the same surgical technique. C2F6 shares the advantages of C3F8 in the management of retinal detachments complicated by proliferative vitreoretinopathy. However its absorption is more rapid as compared to C3F8. This is an advantage with regard to the postoperative disadvantages of gas tamponade. Further clinical use on a larger series of patients is required to confirmed the preliminary results. PMID- 1298774 TI - [Unilateral iris metastasis of cutaneous malignant melanoma]. AB - We describe a case of cutaneous malignant melanoma metastatic to the iris and the angle 31 months after excision of the primary tumor in a 37-year-old caucasian female patient. The patient who had numerous metastases (lung, liver, cerebrum, skin) suffered from secondary glaucoma and died 5 months after the discovery of the intraocular metastases. The glaucoma was treated with medications and cyclocryotherapy. There was no response of the iris metastases to cyclical combined chemotherapy. PMID- 1298775 TI - [A case of intraocular recurrence at a distant site of malignant melanoma of the choroid treated by cobalt 60 disk]. AB - Twenty months after cobalt 60 plaque therapy of a choroidal malignant melanoma, a patient developed an intraocular recurrence at a site distant from and non contiguous to the original lesion that seemed controlled. The characteristics and the possible explanations of this unusual recurrence are discussed. PMID- 1298776 TI - [Presentation of soft implants. Techniques of implantation, the advantages]. PMID- 1298777 TI - [Growth factors in ophthalmology]. PMID- 1298778 TI - [Pigmented seborrheic wart on the skin of the eyelid]. AB - Pigmented tumors of the eyelid are often difficult to identify accurately, as different tumors may have the same clinical presentation. We report the case of a 84 year old female patient who noticed a black tumor of the lower eyelid, with a recent increase in size. Clinically, this lesion was an exophytic tumor of the medial part of the left lower eyelid, respecting the lacrimal punctum and involving the palpebral margin. A surgical excision was performed. Microscopic examination revealed a pigmented seborrheic keratosis, a benign tumor of the epidermis. Histopathology has a key role in the precise diagnosis of pigmented tumors of the eyelid, in which the differential diagnosis concludes sweat gland cysts, pigmented basal cell carcinoma, naevus and uncommon malignant melanoma. PMID- 1298779 TI - [Diagnostic and treatment of unilateral congenital cataract]. PMID- 1298780 TI - Surgical versus orthodontic correction of skeletal Class II malocclusion in adolescents: effects and indications. AB - To clarify the effects of orthodontic versus surgical treatment and to distinguish more clearly those Class II patients who can be treated successfully with orthodontics alone, we compared three groups of adolescents: forty patients treated successfully with orthognathic surgery, 40 patients treated successfully with orthodontics alone, and 21 patients whose orthodontic treatment was judged to be unsuccessful. Successful surgical treatment was accomplished largely by bringing the mandible forward, but this involved vertically repositioning the maxilla, alone or in combination with advancing the mandible, in 40% of the patients. Successful orthodontic treatment resulted from a combination of retraction of the maxillary incisors and protraction of the mandibular incisors; most of the successfully treated group also had significant vertical growth, and 40% had greater than 2 mm anteroposterior growth. The unsuccessfully treated orthodontic patients initially had greater overjet, more severe mandibular deficiency, and greater anterior facial height than those treated successfully; they also had less retraction of the maxillary incisors and less growth during treatment. In Class II adolescents beyond the growth spurt, surgery is likely to be needed for successful correction of the malocclusion if the overjet is greater than 10 mm, especially if the distance from pogonion to nasion perpendicular is 18 mm or more, mandibular body length is less than 70 mm, or facial height is greater than 125 mm. PMID- 1298781 TI - Recovery following orthognathic surgery and autologous blood transfusion. AB - Patients undergoing maxillary surgery, with or without mandibular surgery, were divided into two groups. One surgeon's patients served as controls and did not receive blood unless hemodynamically indicated. The remaining surgeons' patients were transfused regardless of their hemoglobin levels following surgery. An attempt was made to identify benefits or complications associated with the reinfusion of autologous blood, particularly in patients with "low blood loss." Patients were asked to record when they returned to their presurgical level of activity. Of the 46 patients in the study 14 (12 nontransfused, two transfused) were not back to full activity 6 weeks after surgery. Of the 32 patients that reported a return to full activity within the study period, transfused patients reported a significantly quicker return to full activity at 2 weeks, 3 weeks, and 4 weeks postoperatively than did their nontransfused counterparts, even when blood loss at surgery was minimal. No complications have occurred with this practice. PMID- 1298782 TI - The use of asymmetric yaw in the correction of lateral facial defects in hemifacial microsomia deformities: a case report. AB - Treatment of a patient who had hemifacial microsomia and the long-term follow-up are presented. In selected cases, incorporation of an asymmetric yaw in orthognathic surgery can compensate for some of the soft tissue deficiency and asymmetry and produce esthetic results. Early surgical intervention is important to the success of treatment. PMID- 1298783 TI - The use of osseointegration to stabilize a surgical elongation of the maxilla: a case report. AB - Osseointegrated implants placed prior to maxillary downgrafting were utilized to stabilize the repositioned maxilla and interpositional bone graft. Eleven-month follow-up revealed complete healing of the 1.5-cm osteotomy gap and no maxillary relapse. Implant stabilization may be one solution to the relapse associated with inferior repositioning of the maxilla. PMID- 1298784 TI - Prediction of ramus fragment relationship in the surgical correction of facial asymmetries. AB - The Orthognathic Surgery Simulating Instrument is valuable for the presurgical evaluation of patients with dentofacial deformity asymmetry. The case report presents the use of the instrument in the presurgical workup of a patient with a severe facial asymmetry. Advantages over the use of a conventional articulator are also discussed. PMID- 1298785 TI - Orthodontic finalization following therapy with an anterior repositioning splint. AB - After phase I splint therapy for the management of posterior condylar displacement, it is not unusual to find that a posterior open bite has been created. Finalization of a new occlusal position may be effected via occlusal equilibration, prosthodontics, orthodontics, orthognathic surgery, or a combination of these procedures. Stabilizing the occlusion with orthodontics in the new orthopedic jaw position requires a systemic approach. This article outlines a strategy for orthodontic finalization in phase II therapy. The splint guided position is maintained while intra-arch and interarch malocclusions are corrected. The objective in treatment of posterior condylar displacement via splint therapy and orthodontics lies in the provision of a sound condylar position and the movement of the teeth and mandible into a stable and esthetic position. PMID- 1298786 TI - Stability of transient, semirigid pin fixation of sagittal split mandibular osteotomies. AB - Cephalometric records of 16 patients who underwent mandibular lengthening, stabilized with noncompressive pin fixation, were examined retrospectively. Digitization and computer analyses of the cephalometric changes for various time intervals were performed. All linear changes were stable for 13 of the 16 patients over the follow-up period of 2 years. No significant correlation was found between postoperative horizontal relapse and amount of advancement. A high degree of postfixation stability was obtained with very short fixation periods. While further study of this pin fixation technique is indicated, these preliminary results are favorable. PMID- 1298787 TI - Catalase/peroxidase activity in dental pulp. AB - Extrinsic stains on vital teeth are bleached with 30% hydrogen peroxide (H2O2) or carbamide peroxide, H2O2 greatly inhibits the activity of several enzymes. Free H2O2 and carbamide peroxide readily enter the pulp through the coronal wall of the tooth. Nevertheless, adverse effects have been remarkably rare. This study was undertaken to determine whether dental pulp exhibits any catalase or peroxidase activity that might protect it from damage during vital bleaching procedures. Pulpal tissue from healthy human teeth was assayed for catalase and glutathione peroxidase activity. A phosphate buffer extract of the tissue served as the source of the enzymes. The rate of breakdown of H2O2 by the tissue extract was measured and the rate constant for catalase was determined. The catalase activity, defined as microM H2O2 broken down/min/mg wet tissue, was determined and found to be only 2 x 10(-2), which is very low. The fibrous pulpal tissue was found to exhibit virtually no glutathione peroxidase activity. PMID- 1298788 TI - Histomorphometric comparison of canals prepared by four techniques. AB - Numerous methods of root canal preparation have been recommended and used by clinicians. This study used histomorphometrics to determine the area of root canal preparations using four currently popular techniques. Clinicians that were highly skilled in each technique prepared curved canals in acrylic blocks. Each clinician described this technique and discussed the technique with regard to the use of acrylic blocks as compared with dentin. Analysis of the areas of the root canals after preparation revealed a significant difference among the groups. The mean areas after treatment were step-back technique, 17.33 mm2; Cavi-Endo technique, 15.87 mm2; Canal Master technique, 13.56 mm2; and balanced force technique, 17.31 mm2. Photographs of the blocks used in the study were included for inspection by the reader. PMID- 1298789 TI - Apical dye penetration with four root canal sealers and gutta-percha using longitudinal sectioning. AB - The purpose of this study was to compare the level of apical dye penetration when different sealers were used with lateral condensation of gutta-percha. Fifty teeth with single root canals were biomechanically prepared using the step-back technique and irrigation with 15% ethylenediaminetetraacetic acid with cetrimide and 1% NaOCl solutions. The teeth were divided into five groups of 10 teeth each. The control group root canals were filled with laterally condensed gutta-percha without sealer and the other four groups were filled with laterally condensed gutta-percha and either Apexit, Sealapex, Tubli-Seal, or AH-26 sealer. After storage in 100% humidity at 37 degrees C for 48 h, the root surfaces were coated with nail varnish (except at the apex), placed in 2% methylene blue dye solution, and centrifuged at 30 x g for 3 min. The roots were sectioned longitudinally to determine the following mean levels of dye penetration: AH-26, 0.48 mm; Apexit, 1.33 mm; Sealapex, 4.59 mm; Tubli-Seal, 5.58 mm; and gutta-percha alone, 7.99 mm. This study demonstrated that a root canal sealer should be used in conjunction with laterally condensed gutta-percha and that AH-26 sealer had significantly less dye penetration than the other three sealers while Apexit had significantly less dye penetration than Sealapex and Tubli-Seal. There was no significant difference between Sealapex and Tubli-Seal. PMID- 1298790 TI - A comparison of intracanal stresses in a post-restored tooth utilizing the finite element method. AB - The finite element method was used to compare stresses along the inner canal wall in four two-dimensional models of an average maxillary central incisor. The four models evaluated were an intact incisor, an endodontically treated incisor, an endodontically treated crown-restored incisor, and a cylindrical post and crown restored incisor. A horizontal static force, 1 Newton in magnitude, was applied to the lingual surface of each model and the maximum tensile, compressive, and shear stresses were calculated using the general purpose finite element program PAFEC 75. Results indicate that the stress patterns within the root are altered as a result of post insertion. Specifically, the maximum bending stresses are associated with the apical termination of the post, and post placement does not result in a uniform distribution of stress along the canal wall. PMID- 1298791 TI - Thickness of cementum/dentin in mesial roots of mandibular first molars. AB - The mesial roots of 15 human first lower molars, along with the corresponding half of the tooth crown, were studied to determine the thickness of dentin cementum. A device was developed whereby these could be embedded in resin with a precisely known orientation in space. The roots were radiographed in mesiodistal and vestibular-lingual projections, then sectioned perpendicular to the canal axis in the coronal third. Thickness of dentin-cementum was compared on sections and radiograms; results showed that the amount of hard tissue is effectively about one fifth less than that appearing on the radiogram. PMID- 1298792 TI - An in vivo evaluation of the efficacy of ultrasound after step-back preparation in mandibular molars. AB - This study histologically compared the in vivo debridement efficacy of the step back preparation versus a step-back/ultrasound preparation in the mesial root canals of vital mandibular molars. Group 1 consisted of 17 teeth prepared with a step-back technique using intermittent irrigation with 5.25% sodium hypochlorite. Group 2 consisted of 17 teeth prepared with a step-back technique as in group 1 followed by 3 min of ultrasonic instrumentation per canal utilizing a #15 Endosonic file in an Enac unit set at 3.5. An additional 6 ml/canal of 5.25% sodium hypochlorite was used during the ultrasonic preparation. Eight uninstrumented mandibular molars served as histological controls. Following extraction and histological preparation, 0.2-microns cross-sections from the 1- to 3-mm apical levels of the canal and isthmus were evaluated for percentage of tissue removal using an Olympus CUE-2 Image Analysis System. Factorial analysis of variance indicated canal and isthmus cleanliness values were significantly higher, at all 11 apical levels, with the ultrasonic technique. Sample values at the 1-, 2-, and 3-mm levels for the step-back and step-back/ultrasonic techniques, respectively, were: canal, 64% versus 92%, 81% versus 97%, and 90% versus 99.9%; isthmus, 2% versus 46%, 15% versus 60%, and 16% versus 83%. PMID- 1298793 TI - The relationship between clinical symptoms and anaerobic bacteria from infected root canals. AB - The purpose of this study was to investigate the correlation between the composition of bacterial flora from infected root canals and clinical symptoms. The materials evaluated consisted of 28 teeth from 25 patients with apical periodontitis. Eubacterium were found to be significantly related to acute or chronic clinical symptoms and Peptococcus, Peptostreptococcus, and Porphyromonas gingivalis to subacute clinical symptoms. We suggested that Peptococcus, Peptostreptococcus, Eubacterium, Porphyromonas, and Bacteroides were significantly related to percussion pain; Porphyromonas and Bacteroides were significantly related to odor in the infected root canals. Many Bacteroides were isolated from most of the infected root canals. PMID- 1298794 TI - Root canal morphology of mandibular incisors. AB - In this study, 100 mandibular central and lateral incisors were used to determine the number of root canals and their types, the ramifications of the root canal, the location of apical foramina, and the frequency of apical deltas. The teeth were immersed in India ink, decalcified, and cleared. The examination of root canal systems of the teeth was based on Vertucci's classification. Two more root canal types which are not defined in that classification have also been determined and grouped as new types. PMID- 1298795 TI - Endodontic retreatment: a rational approach to root canal reinstrumentation. AB - During nonsurgical endodontic retreatment, endodontic instruments are forced apically to remove the root canal filling material and regain canal patency. Undiscriminating burrowing down the canal in the apical direction may be fruitless and harmful. To avoid complications, the dentin overhanging the canal orifice must be removed and an unobstructed access established to the root filling material, so as to facilitate its removal. Reinstrumentation of the filled canal must take into consideration the nature of the filling material and the physical properties of endodontic instruments, as well as the dynamic aspects of canal preparation. This article discusses the mechanical considerations pertaining to root canal retreatment and outlines a step by step rationale approach to retreatment. PMID- 1298796 TI - Zebra XII. Part I. Large-cell lymphoma. PMID- 1298797 TI - Effect of moisture and aging on gutta-percha. AB - The purpose of this article was to study the plasticizing effect of controlled levels of different humidities on native and commercial gutta-percha samples. It was expected that the results might provide the practicing endodontist with invaluable insight into the mechanical properties of commercial gutta-percha cones (i.e. retrievability, malleability, flexibility, torsional, and bending ability). The "conditioning" of the gutta-percha samples depended greatly on the percentage of compatible and incompatible substances. Mixtures of native gutta percha with compatible substances (e.g. wax) showed greater elongation, tensile strength, and number of rotations but lower deformation angle than mixtures of native gutta-percha with incompatible substances (e.g. salts, metal oxides). The observed lower values for tensile strength and torsional strain and higher value for elongation and number of rotations for wet samples compared with the dry ones were attributed to the plasticizing effect on gutta-percha of the insertions of water molecules in the polymer chains. PMID- 1298798 TI - Delineation of cytotoxic concentrations of two dentin bonding agents in vitro. AB - Until adhesiveness of dentin bonding agents and other restorative materials to dental structures can be assured, microleakage into resulting "gaps" and dentin permeability will remain major concerns in cases of pulpal irritation. The objectives of the present study were to (a) delineate the kinds and levels of metabolic cytotoxicity of the GLUMA and Scotchbond 2 systems as well as glutaraldehyde and 2-hydroxyethylmethacrylate, and (b) compare the effects of these same materials after diffusion through dentin discs approximately 0.5-mm thick. In monolayer cultures, glutaraldehyde was much more cytotoxic than 2 hydroxyethylmethacrylate. However, GLUMA sealer and Scotchbond 2 adhesive exhibited similar cytotoxicity in monolayer cultures. After diffusion through dentin, glutaraldehyde and 2-hydroxyethylmethacrylate effects were diluted 14.7 and 26.7 times, respectively. The postdiffusional effects of the GLUMA and Scotchbond 2 systems were not significantly different and less than those effects in monolayer cultures. This study should help in the evaluation of possible causes of pulpal irritation following restorative procedures. PMID- 1298799 TI - Dentin removal efficiency of six endodontic systems: a quantitative comparison. AB - The dentin removal efficiency of current endodontic systems, based on the amount of dentin removed in 1 mm of canal axial length, was determined for working times of 1 and 2 min. Six endodontic systems were compared: The Giromatic with Heli Giro files, the Sonic-Air with Shapers, the Mecasonic with Shapers, the Cavi-Med with K files, the Cavi-Med with Shapers, the Excalibur with its own K files. Generally speaking, the efficiency of each device depends on the duration of instrumentation, on the type of file used, and on its mode of activation. For 1 min of instrumentation, the Mecasonic+Shaper was the most efficient system. For 2 min of instrumentation, the original adaptation of the Shaper on the Cavi-Med gave the highest activity. Concerning the files used in ultrasonics, the Shaper seems to be more efficient than the K file. As for the sonics, the Excalibur+file system gave results comparable to those of the Mecasonic+Shaper; both of these devices were twice as efficient as the Sonic-Air+Shaper. PMID- 1298800 TI - Efficacy of several concentrations of sodium hypochlorite for root canal irrigation. AB - Sodium hypochlorite (NaOCl) has been recommended for irrigation during root canal preparation. This investigation used scanning electron microscopy to examine instrumented and uninstrumented surfaces in the middle third of root canals following the use of several concentrations of NaOCl (5.25%, 2.5%, 1.0%, and 0.5%). NaOCl was delivered with either an endodontic irrigation needle or an ultrasonic device. All of the concentrations of NaOCl with either delivery system were very effective in flushing out loose debris from the root canals. A smear layer with some exposed dentinal tubules was seen on all instrumented surfaces regardless of concentration of NaOCl or irrigation device. NaOCl in concentrations of 5.25%, 2.5%, and 1% completely removed pulpal remnants and predentin from the uninstrumented surfaces. Although 0.5% NaOCl removed the majority of pulpal remnants and predentin from the uninstrumented surfaces, it left some fibrils on the surface. PMID- 1298801 TI - Microleakage comparison of apical seal of plastic versus metal Thermafil root canal obturators. AB - This study compared the apical seal of plastic versus metal Thermafil obturators in extracted human teeth. The obturated teeth were evaluated radiographically for the extent and adaptation of the filling obturator. No difference was seen between plastic and metal for over- or underfilling. Voids were seen more often in smaller sizes of both plastic and metal obturators. Obturated teeth were stained in India ink, decalcified, and cleared. Microleakage evaluation of the transparent teeth showed no statistical difference between metal and plastic obturators. PMID- 1298802 TI - Effect of precurving endosonic files on the amount of debris and smear layer remaining in curved root canals. AB - Endosonic files are prone to constraint; this reduces their efficiency, particularly in the apical third and in curved root canals. Precurving the file may reduce constraint, thereby improving the file's ability to debride. This investigation was undertaken to compare both straight and precurved endosonic files as to debris and smear layer removal. Thirty-six curved root canals were randomly allocated into six groups. Each group was prepared using a step-down technique, then instrumented with either a straight or precurved endosonic file of size 15, 20, or 25. The tooth roots were split and examined under the scanning electron microscope. Blind examinations were made for debris and smear layer removal and evaluation scores were analyzed using a log linear approach. The root canals instrumented with the precurved files had a significantly lower debris score than those prepared with straight files. Precurving did not affect smear layer removal. In conclusion, precurving of files decreased the amount of debris but did not affect smear layer removal. PMID- 1298803 TI - Characterization of total membrane protein of Porphyromonas endodontalis. AB - Porphyromonas endodontalis strains ATCC 35406, HG 181, and HG 413 were cultured in an enriched broth medium, and growth curves were determined. Total membrane protein profiles of cells, harvested either from exponential phase or from stationary phase of growth, were studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The protein profiles indicated that the three strains shared three major proteins, designated A, B, and C, with molecular masses of 59, 43, and 41 kDa, respectively. In addition, the strains showed homology among the majority of the minor proteins. However, some minor proteins were unique for each strain. Two common minor proteins with molecular masses of 56 and 51 kDa were weakly expressed or absent in membrane preparations from cells of the early exponential phase, while they were present in membrane preparations from cells harvested in the late phase of growth. The major and minor membrane proteins may play a role in the interaction between P. endodontalis and the host. In addition, the membrane proteins may play an important role in the physiology of this endodontic pathogen. PMID- 1298804 TI - Factors associated with endodontic treatment failures. AB - Two hundred and thirty-six cases of endodontic treatment failures, none of which had advanced periodontal disease, postperforations, or root or crown fractures were analyzed clinically, radiographically, and histobacteriologically to determine the major factor(s) for treatment failures. It was found that there was a correlation between bacterial infection in the canal system and the presence of periradicular rarefaction in endodontic failures. This report provides evidence indicating that the major factors associated with endodontic failures are the persistence of bacterial infection in the canal space and/or the periradicular area and the presence of preoperative periradicular rarefaction. The apical extent of root canal fillings, i.e. underfilled, flush-filled, or overfilled, seems to have no correlation to treatment failures. PMID- 1298806 TI - Zebra XII. Part 2. Large-cell lymphoma. PMID- 1298805 TI - Endodontic treatment of fused teeth. AB - A case is reported documenting successful treatment of suppurative periradicular periodontitis involving a maxillary central incisor fused with a supernumerary tooth. Endodontic therapy was performed and partial resolution of the lesion was evident at the 1-yr recall and further resolution at the 16-month recall. PMID- 1298807 TI - The challenge of peer review. PMID- 1298808 TI - Taking ethics seriously. Building a professional community. PMID- 1298809 TI - Employment and utilization of dental hygienists in Minnesota healthcare facilities. AB - This study surveyed a representative sample from the entire listing of accredited hospitals and licensed nursing homes in Minnesota with bed accommodations of 100 or more. The purpose of the study was to determine (1) the current providers of oral healthcare to patients/residents in the selected facilities; (2) the employment and utilization of dental hygienists in these facilities; and (3) reasons for not employing a dental hygienist. A questionnaire was designed and sent to 147 facilities in November 1986 with a follow-up in January 1987. A total of 118 questionnaires were returned, resulting in a response rate of 80.3%. The results revealed that less than half of the facilities utilized a dental hygienist. In the majority of facilities surveyed, consulting dentists, registered nurses, licensed practical nurses, and nurse's aides were identified as those responsible for providing oral healthcare services. Insufficient funds was the primary reason identified by these facilities for not employing a dental hygienist. Dental hygienists employed in healthcare facilities provided therapeutic treatment and oral hygiene education services to staff and patients. In comparison, visiting dental hygienists tended to perform more staff training than patient education or therapeutic services. Most respondents indicated that a dental hygienist employed by their facility would improve the oral health status of their patients or residents. A large number of respondents appeared to be uncertain of the role of a dental hygienist in their healthcare facilities. Educational efforts are needed to increase the understanding of healthcare administrators and the public of the benefits of employing dental hygienists. PMID- 1298810 TI - The local drug delivery of tetracycline, metronidazole, and chlorhexidine in periodontal therapy. PMID- 1298811 TI - Dental hygiene recruitment and retention: marketing to the female adult reentry student. PMID- 1298812 TI - A visit to the office of Dr. S.J. Barber--1893. PMID- 1298813 TI - Chemical dependencies in dental professionals and their patients. PMID- 1298814 TI - Author and subject indexes to volumes 445-458 (January-December 1992). PMID- 1298815 TI - The use of lasers in implantology: an overview. AB - While lasers have been utilized in oral surgery for many years, the recent advent of improved delivery systems together with a range of laser wavelengths from which to choose has promoted interest in the application of lasers in other areas within dentistry. This paper provides an overview of the use of lasers in laboratory and clinical techniques used in implantology, with particular reference to carbon dioxide, Nd:YAG, argon, and erbium:YAG lasers. From a consideration of how particular laser wavelengths interact with metallic and ceramic implant materials, and with bone and soft tissues, principles for the rational and safe use of lasers are deduced. PMID- 1298816 TI - Load transfer from endosteal implants to supporting bone: an analysis using statics. Part one: Horizontal loading. AB - By use of engineering statics, the amount of force transferred to the crestal bone from a horizontal occlusal load, relative to the implant length necessary to support that load, was analyzed for hypothetical instances when the implant was embedded in a uniform mass of bone and when it was bicorticated. The analysis revealed that implants longer than 12 mm will not significantly reduce force transfer proportionately to the increased length. Also, bicortication will mitigate force transfer to the crestal bone. Finally, the amount of force transfer is directly proportional to the height of load application from the crestal bone. PMID- 1298817 TI - Load transfer from endosteal implants to supporting bone: an analysis using statics. Part two: Axial loading. AB - Engineering statics was used for the analysis of axial occlusal load transfer by a dental implant to the supporting bone. The analysis revealed that an implant can be totally supported by trabecular bone. Also, an implant of only 10 mm in length with a 4-mm diameter can transmit average maximum biting forces to the supporting bone within the physiologic strain limits of the bone. PMID- 1298818 TI - Torsional stability of HA-coated and grit-blasted titanium dental implants. AB - Hydroxylapatite (HA)-coated and grit-blasted (non-HA-coated) titanium dental implants were inserted into healed extraction sites of canine mandibles. After six weeks, the animals were killed and the implants mechanically tested in torsion to failure. Interface attachment strength, implant/tissue compatibility, integrity of the HA coating, and the location of interface failure were evaluated. Mechanical testing demonstrated an interface torsional strength of 3.98 +/- 0.93 MPa for the HA-coated implants and 2.25 +/- 0.65 MPa for the grit blasted implants. This represents a 76.9% improvement in the maximum torsional interface strength, and is statistically-significant (p = 0.0004). On qualitative histologic analysis, interface failure was seen to occur primarily at the HA/implant interface, although failure through the HA coating and regions of bone/HA interface failure were observed. The HA-coated implants had bone in direct apposition to their surface with no fibrous tissue interposition. The grit blasted implants also had regions of direct bone-implant apposition, but these areas were limited to a smaller proportion of the total interface area. There was no evidence of breakdown or change in thickness of the HA coating. PMID- 1298820 TI - The use of a new form of allograft bone in implantation or osseointegrated dental implants--a preliminary report. AB - The use of and early results with a new form of demineralized allograft bone tissue with the immediate placement of a dental implant are described. No occlusive membranes were utilized. GRAFTON Allogeneic Bone Matrix (ABM) is processed from human cortical bone into a thick gel consistency and packaged sterile in disposable syringes. The material was utilized in seven patients with seven implants. New bone formation was noted and, with the exception of two implants with a small amount of thread exposure, complete. It appears that treatment with the bone-grafting material produced clinical results similar to those reported with the use of barrier membranes and may provide an alternative to guided tissue regeneration. Further investigation appears warranted. PMID- 1298819 TI - A comparison of femoral and mandibular animal models for the evaluation of HA coated implants. AB - The application of hydroxylapatite coatings promises marked improvement in the rapidity and durability of osseointegration for both dental and orthopedic metallic implants. Standard methods for the in vivo assessment of the performance of experimental implants include canine mandibular and femoral transcortical implantations. This study compared the results of the two procedures by use of similar HA-coated titanium implants. The results indicate that the rapidity of osseointegration and the maximum attachment strength for mandibular dental implants approximate those of the femoral transcortical implants, especially at longer post-operative intervals. We conclude that the two models are comparable for the purpose of evaluating the performance of this type of implant and can be used interchangeably by dental and orthopedic implant designers. HA-coating of titanium implants provides extensive osseointegration in both mandibular and long bone models, with similar mechanical attachment strengths and histologic appearance. PMID- 1298821 TI - Simulated implant surgery in rabbit long bones: a descriptive study. AB - The objectives of this study were: (a) to observe and describe the variability of bone healing in implant receptor sites which were prepared in rabbit femurs by use of different surgical methods; and (b) to determine if the animal model which was used was suitable for the detection of differences in healing reactions in implant receptor sites which were prepared by different surgical methods. Three 3 mm-wide implant receptor sites were prepared in the right and left femurs of four large New Zealand white rabbits. The surgical parameters used in preparation of the different sites included: low speed with no irrigation (LSO); low speed with internal irrigation only (LSI); low speed with external irrigation only (LSE); high speed with no irrigation (HSO); or high speed with external irrigation only (HSE). The sites were randomized so that each animal had one of each type of site in either the right or left femur. A non-treated control site was located in each animal for comparison with experimental sites. The animals were killed at 7, 14, 21, and 28 days post-operatively. The resultant samples were fixed, embedded, sectioned, and stained with basic fuchsin and toluidine blue. The results indicated that this was probably not a suitable animal model, since no discernible differences were detected in the various healed sites. PMID- 1298822 TI - A study of osteoporosis as it relates to metabolic manifestations in edentulous women. AB - Among some patients, regardless of age, the jaw loses bone mass, leading to loosening and falling out of otherwise healthy teeth. This study seeks to establish whether this bone loss is associated with the metabolic manifestations of other forms of localized decalcifications, such as in Paget's disease, or with generalized osteoporosis. Sixteen women being fitted with dental implants to compensate for bone losses provided 24-hour urine samples for the quantitative determination of calcium and galactosyl hydroxylysine, a bone collagen metabolite. These patients provided demographic information, relevant medical, dental, and dietary history, a profile of their current medications, and the status of their smoking and exercise habits. Urinary excretion of galactosyl hydroxylysine, which is increased in the presence of progressive increased bone resorption, remained within normal values in the patients of this study. These results suggest that the thinning of the jaw bones and subsequent tooth loss of these subjects were osteoporotic processes too limited and too localized to produce measurable increases in urinary bone metabolites. PMID- 1298823 TI - The position and course of the mandibular canal. AB - Twenty-nine human cadaver mandibles were dissected longitudinally and cross sectionally for determination of the precise location of the inferior alveolar nerve, artery, and vein. The neurovascular bundle was located in contact with, or very close to, the lingual cortical plate until it reached the mental foramen. Anterior to the mental foramen, the neurovascular bundle was not a distinct entity and was located close to the labial cortical plate. In the body of the mandible, the neurovascular bundle was located about one centimeter above the mandibular inferior border. The distance from the lateral border of the neurovascular bundle to the external surface of the buccal plate was usually half a centimeter in the molar and premolar regions. The mandibular canal was usually formed by a thin bony plate that, grossly, had more of an appearance of trabecular bone; in only a few mandibles was there a thin layer of cortical bone. PMID- 1298824 TI - Spark erosion fixed/detachable prosthesis for the completely edentulous maxilla. AB - A technique is described for restoration of the completely edentulous maxilla. From six to eight root-form implants are surgically placed in the edentulous maxilla. A hybrid overdenture is constructed by use of a two-degree tapered precision milled primary bar. A cast overdenture prosthesis is constructed over this bar, and precision attachments are spark-erosion-processed to the primary and secondary prosthetic components. The technology described in this article allows for an intimate fit of the various prosthetic components. This prosthetic protocol permits maximum retention and stability of the prosthesis and solves many problems which are encountered in the oral rehabilitation of the edentulous maxilla. PMID- 1298825 TI - Bone regeneration and tissue acceptance of human fascia lata grafts adjacent to dental implants: a preliminary case report. AB - The biologic principle of guided tissue regeneration (GTR) has been studied extensively in hopes of regenerating alveolar bone. Various materials have been utilized as regenerative membranes; however, all materials have disadvantages, and the ideal membrane material is yet to be identified. In this case report, human freeze-dried fascia lata strips were used as a regenerative barrier membrane in conjunction with the placement of endosseous root implants and demineralized, freeze-dried bone allograft. The major advantage in the use of human fascia lata for guided tissue regeneration is that a second procedure to remove the material is not necessary, and the fascia is accepted by the surrounding tissues without complication. There is acceptance of four endosseous root-form dental implants that were immediately placed into fresh extraction sockets and covered with demineralized freeze-dried bone allograft (DFDBA), with human freeze-dried fascia lata used to serve as a biocompatible, collagenous, regenerative augmentation membrane over the dental implants. The biologic concept of GTR is clinically applied to increase the dimensions of the edentulous, maxillary alveolar ridge with use of human freeze-dried fascia lata barrier membranes. PMID- 1298826 TI - Hard tissue replacement implants. PMID- 1298827 TI - [Emergency medical aid to patients with craniocerebral trauma in the prehospital period]. AB - On the basis of analysis of more than 5000 observations of the sufferers admitted to the Kiev Research Institute of Neurosurgery for acute craniocerebral trauma from 1975 to 1991, quality of giving medical aid at the prehospital period was studied. Of most importance, are the measures directed at struggle against respiratory disorders, disturbances in cardio-vascular activity, shock, hemorrhage. PMID- 1298828 TI - [Prevention and treatment of purulent inflammatory complications of open craniocerebral trauma with decamethoxine ]. AB - In the work based on the analysis of observation of 154 sufferers with an open craniocerebral trauma, the positive therapeutic and preventive action of agueous solutions of decamethoxine is shown. PMID- 1298829 TI - [Hyperbaric oxygenation in the comprehensive therapy of young and middle age patients in the acute period after mild craniocerebral trauma]. AB - The results of treatment of 107 young and middle aged sufferers with mild craniocerebral trauma have been analysed. The regimen for use of hyperbaric oxygenation contributing to normalization of general cerebral, focal disorders in high nervous and psychic activity, prevention of certain posttraumatic complications has been developed. PMID- 1298830 TI - [Cerebrospinal fluid sorption in the treatment of severe craniocerebral trauma in the acute period]. AB - The effectiveness of the use of liquorosorption in treatment of 6 sufferers with severe craniocerebral trauma is shown. PMID- 1298831 TI - [Predictive value of the combined electro-, echo-, and rheoencephalographic studies in the acute period after severe craniocerebral trauma complicated by intracranial hemorrhage]. AB - On the basis of the data of complex studies, the signs of changes in the bioelectrical activity of the brain, state of its middle structures and hemodynamics in favourable and lethal outcome of craniocerebral trauma complication by intracranial hemorrhage have been established. Early detection of the signs mentioned contributed to improvement in the results of treatment at the acute period. PMID- 1298832 TI - [Correction of lipid peroxidation disorders of patients in the acute period after craniocerebral trauma]. AB - In sufferers at the acute period of mild and severe craniocerebral trauma, the processes of peroxide oxidation of lipids become essentially more active. The antioxidative function of an organism decreases. Changes in the metabolic processes are the most pronounced in patients under 44 years and in women of different age in severe craniocerebral trauma. The authors recommend to include into the complex of treatment in craniocerebral trauma the intensive antioxidant therapy together with surgical intervention. PMID- 1298833 TI - [Brain concussion in patients with chronic vascular, gastrointestinal and pulmonary diseases]. AB - Examined were 317 patients with brain concussion ranging in age from 16 to 75 years. Of them in 133 (41.91%), chronic diseases (I-II degree chronic insufficiency of cerebral circulation, arterial hypertension, chronic cholecystitis, gastric and duodenal ulcer disease, chronic bronchitis, bronchial asthma) were revealed. Peculiarities of the course of brain concussion in these patients are noted. The author stresses that it is necessary to take into account chronic diseases when observing and treating the sufferers with brain concussion. PMID- 1298834 TI - [Plastic reconstruction fo cranial vault defects]. AB - Peculiarities of performance of the reconstructive operation performed in 350 patients at primary surgical treatment, or later on, at the period of primary treatment of a patient at a hospital and at his readmission with the aim of cranioplasty are considered. The authors recommend to perform the reconstructive operation in presence of a cranial vault defect at the time of primary surgical treatment, or 2-5 weeks later, when preparing a patient for such an operation. PMID- 1298835 TI - [Specifics of diagnostic and surgical approach in the treatment of complicated injuries of the extremities in the acute period]. AB - The results of treatment of 82 patients with associated injury to the nerves of the extremities have been analysed. In rupture of a nerve, the clinico-neurologic examination has the most informative value, in its partial injury, the performance of electrophysiologic investigations is mandatory. A degree of restoration of the extremity function depends on timeliness and adequacy of the operation. PMID- 1298836 TI - [Intensification of surgical therapy of traumatic injury to the median and ulnar nerves in the acute period]. AB - The results of experimental development of the use of Quercitrol, the inhibitor of leukotrienes, and helium-neon laser acupuncture for the treatment of antiinflammatory operative neuroma decelerating the process of neural tissue regeneration are presented. The positive data of the experiments have been confirmed in the clinic. PMID- 1298837 TI - [Clinico-morphologic evaluation of susceptibility of glioblastoma to antiblastic therapy]. AB - Pathomorphology of a cerebral glioblastoma in 82 patients was studied. The most pronounced regressive changes in the glioblastoma occurred under the influence of a complex of antiblastic treatment, including polychemo- and immunotherapy, radiation therapy. A high degree of damaging effect on a glioblastoma tissue correlated with the longest lifetime of the patients--(22.8 +/- 2.6) mos. Of these patients, 26% survived more than 24 mos, 17%--more than 36 mos. In patients with chemo-resistant glioblastoma which retains morphologically a stability of its histologic structure, the mean survival almost didn't differ from that in the control group. Only few patients survived more than 1 year. PMID- 1298838 TI - [Acute disorders of adrenal function in supratentorial meningioma]. AB - Of the 128 patients operated on for meningioma of supratentorial location in 52 (23.9%), hemorrhage into the adrenal tissue was revealed. Clinical diagnosis of this pathology is difficult. Pathogenetically, hemorrhage into the adrenal tissue should be considered as manifestation of generalized vascular disorders in complicated postoperative course, which are associated with significant functional strain of the endocrine system resulting from stress reactions. PMID- 1298839 TI - [Clinico-diagnostic value of the immunologic parameters of blood and cerebrospinal fluid in patients with a tumor of the posterior cranial fossa]. AB - In 37 patients with a tumor of the posterior cranial fossa, the immunologic indices of the spinal fluid, blood serum and tumor contents were studied. It was established that changes in the immunologic indices (intrathecal synthesis of IgG and IgA, production of the immunoregulatory factors of cellular immunity, severity of lesion of the brain structures) depended on a degree of tumor anaplasia and age of the patients. These findings can be used for diagnosis of cerebral neoplasms of different degree of malignancy with regard for the age of a patient. PMID- 1298841 TI - [Experience with surgical treatment of endemic and diffuse toxic goiter]. AB - The results of operative treatment of 1336 patients operated on for goiter are presented. In presence of nodules in the thyroid gland, subtotal resection of a lobe, or the lobes of the gland was performed, in suspected malignant tumor--its extirpation. PMID- 1298840 TI - [Surgical treatment of nodular goiter after the accident at the Chernobyl nuclear power station]. AB - The data on incidence of goiter in inhabitants of Kiev province for 5 years after Chernobyl accident, increase in number of operations performed for nodular forms of autoimmune thyroiditis and thyroid cancer are presented. PMID- 1298842 TI - [Prevention of acute purulent inflammatory diseases of the fingers and hand with decamethoxine]. AB - Resulting from disease-prevention work among population of the district, use of BF-6D glue for treatment of microtraumas to skin of the hands, the number of patients with inflammatory diseases reduced by 14.7%. PMID- 1298843 TI - [Indications and technique of conservative surgery in renal cancer]. AB - The organ-preserving surgical intervention for renal cancer was performed in 42 patients. Five-year survival was 64.4%. PMID- 1298844 TI - [One-stage operations in bilateral nephrolithiasis]. AB - The results of treatment of 60 patients with bilateral nephrolithiasis undergoing one-stage operations are presented. PMID- 1298846 TI - [Early diagnosis of acute postoperative hepatic insufficiency in surgical patients]. AB - An original method for diagnosis of hepatic failure at the early postoperative period is described. Diagnosis of hepatic failure was confirmed in 98% of patients, in 2%, the diagnosis has proved to be uncertain. PMID- 1298845 TI - [Effectiveness of combined spinal anesthesia]. AB - Combined spinal anesthesia with the use of hyperbaric solution of lignocaine at an average dose of (69.4 +/- 1.4) mg and morphine hydrochloride at a dose of 0.3 mg was used in 50 patients with II-IV degree anesthesiologic risk during one stage appendectomy. Effective intraoperative anesthesia was achieved in (96.2 +/- 2.5) % of cases. Duration of postoperative analgesia was (26.8 +/- 1.1) h. Suppression of breathing, hyperalgesia on termination of the effect of a local anesthetic were not noted. In (50.1 +/- 1.7) % of the patients, intraoperative hypotension was revealed. After the operation, nausea was noted in (20 +/- 11.5) % of these patients, vomiting--in (6.0 +/- 2.3) %, itch at the site of puncture- in (22.0 +/- 10.4) %, shiver--in (2.0 +/- 1.4) %. PMID- 1298847 TI - [Therapeutic preventive measures for protection of spinal marrow in the acute period after vertebro-spinal trauma]. AB - In accordance with the pathophysiological changes in the spinal cord in trauma, the authors recommend to pay the main attention to normalization of an anatomo morphological disorders, prevention of biochemical shifts and restoration of hormonal background. The scheme suggested should be assumed as a basis for tactics of treatment of the sufferers with a vertebro-spinal trauma. PMID- 1298848 TI - [Pulse-leukocytic-temperature index of intoxication]. AB - The expediency to use for assessment of the severity of organism intoxication a pulse-leukocytic-temperature index of intoxication, which takes into account the leukocytic index of intoxication, body temperature, pulse, is showa. PMID- 1298849 TI - [Omentoplasty of bronchial fistula and pleural empyema]. PMID- 1298850 TI - [Splenomegaly simulating a tumor of the left kidney]. PMID- 1298851 TI - [Bladder al fistula and abscess of the gluteal region caused b a foreign body in the urinary bladder]. PMID- 1298852 TI - [Incarcerated umbilical hernia with necrosis of the ileum and right colon]. PMID- 1298853 TI - [A method for elimination of eversion dislocation in fractures of the ankles]. PMID- 1298854 TI - [A cannula for disinfecting the abdominal cavity]. PMID- 1298855 TI - [Changes in cerebral blood circulation in brain injuries complicated with alcohol intoxication]. PMID- 1298856 TI - [Melanoma of the spinal pia mater]. PMID- 1298857 TI - [ Clinical symptoms , diagnosis and complications of common renal cyst in children]. PMID- 1298858 TI - [Principles of emergency aid in craniocervical trauma of divers]. AB - On the basis of analysis of 113 cases, peculiarities of giving emergency aid to the sufferers with craniocervical trauma in divers were studied. PMID- 1298859 TI - [One-stage surgical treatment of calculous cholecystitis and urolithiasis]. PMID- 1298860 TI - [Spontaneous rupture of the urinary bladder]. PMID- 1298861 TI - [Open penile injury]. PMID- 1298862 TI - [Methods of treatment in traumatic uterine injuries ]. PMID- 1298863 TI - [A case of large osteochondroma of the breast bone]. PMID- 1298864 TI - [Mediastinal ganglioneuroma]. PMID- 1298865 TI - [Isolated and complicated heart injuries]. PMID- 1298866 TI - Purification and characterization of an immunodominant 36 kDa antigen present on the cell surface of Clostridium difficile. AB - The 36 kDa antigen represents the major EDTA-extracted protein of Clostridium difficile strains belonging to electrophoretic group 2. Antibodies to this antigen are found in sera of patients with C. difficile-associated diarrhoea. The 36 kDa antigen was extracted from C. difficile C253 by EDTA and purified by gel filtration (Sephacryl S300) and ion exchange chromatography (DEAE-Trisacryl M). The molecular weight of the purified protein was 36 kDa as determined by SDS PAGE, also in non-reducing conditions. By gel filtration, the molecular size appeared to be 72 kDa and was not modified by the presence of EDTA or SDS in the column buffer. Since IEF showed a single isoelectric form of pI 4.6, the protein could be a homodimeric molecule. Immunofluorescence demonstrated that the 36 kDa antigen was located on the surface of the C. difficile cell. Monospecific antiserum raised in rabbits reacted positively with the 36 kDa protein of most group 2 C. difficile strains isolated from antibiotic-associated diarrhoea (AAD) outbreaks in Italy and other European countries. PMID- 1298867 TI - The virulence plasmid does not contribute to growth of Salmonella in cultured murine macrophages. AB - The virulence plasmid, characteristic of many serovars of Salmonella sp., and specifically its spv genes, promote intracellular growth of the bacteria in the liver and spleen and are essential for the virulence of these Salmonella serovars in the mouse. In an attempt to establish an in vitro model for studying its function, we evaluated its effect on the intracellular growth of the bacteria in macrophages in culture. We used a number of different macrophage-like cell lines (J774-A.1, IC-21 and PU5-1.8), as well as peritoneal or splenic macrophages from genetically Salmonella-sensitive (Itys, BALB/c) or resistant (Ityr, C3H/HeN) mice, and at different states of activation, stimulated in vivo or in vitro with lipopolysaccharide and/or recombinant gamma interferon. These were found to differ in their ability to suppress or sustain intracellular growth of several Salmonella serovars, but in all cases the growth was independent of the spv genes. PMID- 1298868 TI - Changes in the structure of the cell surface carbohydrates of the chinchilla tubotympanum following Streptococcus pneumoniae-induced otitis media. AB - Streptococcus pneumoniae (Spn) are among the most frequently isolated pathogens in acute otitis media (AOM) and in otitis media with effusion (OME). Recently, the specific receptor for Spn has been identified as the trisaccharide unit Gal beta 1-4 GlcNAc beta 1-3 Gal beta with GlcNAc beta 1-3 Gal beta as the principal binding site. During the colonization of mucosal surfaces, pneumococci produce a variety of enzymes. This study was conducted to identify any resulting changes in the cell surface carbohydrate structure due to the action of these enzymes during pneumococcal otitis media (OM) in chinchillas. Using a lectin histochemical method with seven different lectins (SNA, LFA, WGA, Succ WGA, BSL II, PNA, ECL), the labeling pattern revealed not only the removal of the terminal sialic acid, but also the exposure of N-acetyl-glucosamine. These results suggested that Spn produced enzymes uncover part of their own receptor structure and thus may facilitate adherence and subsequent infection. PMID- 1298869 TI - Proliferative and T-cell specific interleukin (IL-2/IL-4) production responses in spleen cells from mice vaccinated with aroA live attenuated Salmonella vaccines. AB - T-cell responses were studied in mice immunized with the Salmonella typhimurium aroA SL3261 live attenuated vaccine strain. T-cell responses in the spleen, both in whole cell populations and in nylon wool non-adherent (T-cell enriched) cells, were studied in vitro as proliferation by incorporation of tritiated thymidine and production of T-cell specific cytokines [IL-2 (interleukin-2)/IL-4]. Stimulating antigens included whole Salmonella lysates and purified lipopolysaccharide (LPS), both untreated and after alkaline hydrolysis to prevent the non-specific mitogenic effect of LPS. Strong proliferative responses were obtained with untreated whole cell extract and LPS, which were decreased by polymyxin B (PB). Alkaline detoxification of the antigens decreased the proliferative response of nylon-wool non-adherent populations to LPS, but greatly increased their response to the Salmonella extract. Surprisingly, PB also reduced proliferation to detoxified LPS. Little or no IL-2/IL-4 production was seen in response to LPS or purified polysaccharide antigens, while there was a strong IL 2/IL-4 response to whole cell lysate, again markedly increasing after alkaline treatment. The results suggest that the T-cell response elicited by immunization with live Salmonella aroA vaccines in mice recognizes antigens other than LPS determinants, and that estimation of T-cell responses to Salmonella antigens by proliferation alone may yield misleading results. PMID- 1298870 TI - [The role of the endogenous opioid system in the pathogenesis of polycystic ovary syndrome: the altered neuroendocrine regulation of GnRH-LH is corrected after clomiphene therapy]. AB - To investigate whether inappropriate LH secretion in Polycystic Ovary Syndrome (PCO) was related to a reduction of inhibitory opioid control on the GnRH-LH system, 23 women affected by PCO (12 obese, BMI: 37.1 +/- 3.9 and 11 non obese, BMI: 21.5 + 2.4) and 19 fertile women (10 obese, BMI: 38.8 + 1.8 and 9 non obese, BMI: 20.1 + 1.5) were studied. Plasma levels of Beta-Endorphin (B-Ep) in basal condition and LH and FSH serum levels following acute administration of naloxone (0.1 mg/kg e.v.) were evaluated in the PCO and control groups. Moreover, in order to investigate whether the neuroendocrine abnormalities in PCO are a primary hypothalamic defect or secondary to an inappropriate feedback of gonadal steroids, the LH response following Naloxone administration was evaluated again after two months of clomiphene therapy (50 mg p.os ones a day for 5 days). The women affected by PCO had increased LH/FSH ratio, testosterone levels (P < 0.001, P < 0.01) and significantly decreased T/E2 ratio, SHBG levels compared to the normal women (P < 0.01, P < 0.001). B-Ep plasma levels in PCOs OB and PCOs nOB (6.13 + 1.2 Pmol/L, 4.8 + 0.4 Pmol/L) were similar to those observed in obese and non obese control women (7.2 + 2.5 Pmol/L, 4.2 + 1.3 Pmol/L), respectively. In the PCO and control groups naloxone induced a significant increase of FSH and LH levels. Thus the area under the curve of LH and FSH was significant higher after naloxone, than following saline infusion both in PCO (P < 0.01, P < 0.05) and controls (P < 0.001, P < 0.001). However, in PCO the post naloxone FSH increase was similar to that found in fertile women, while the LH increase post naloxone was lower than that observed in controls (50 + 32.4% vs 101.6 + 36.7%; P < 0.01). Particularly in PCO with LH/FSH ratio equal or higher than 3, no significant variation of LH levels was found after naloxone. Moreover the LH increase post naloxone was similar in PCO OB (46 + 19.8%) and in PCO nOB (49.9 + 13.1%), correlated negatively with LH basal levels (P < 0.02), LH/FSH (P < 0.005), E1/E2 (P < 0.005) and was independent of T/E2, BMI and duration of the disease. Following clomiphene treatment, the LH response after naloxone was significantly higher than that observed before treatment (from 9.4 + 4.2 mUI/ml to 16.5 + 3.9 mUI/ml, P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1298872 TI - [Acute suppurative thyroiditis in a patient with prior subacute thyroiditis]. AB - Acute suppurative thyroiditis is an uncommon thyroid disorder usually caused by bacterial infection. The most common route of infection is a fistula that originates from the fundus of the pyriform sinus. Pre-existing thyroid disease, most commonly nodular goiter, has been reported to be present in acute suppurative thyroiditis. A 44 year old man presented a subacute thyroiditis, resolved by nonsteroidal antiinflammatory treatment. One year later, the patient abruptly complained of fever and painful swelling in the thyroid region. A relapse subacute thyroiditis was diagnosed and prednisone treatment was started. A few days later owing to a worsening of the pain and of the clinical features the patient was referred to our department. He presented dysphagia and he was feverish, the overlying skin of the neck swelling was erythematous and warm. There was a neutrophilia (83.7%). Plasma FT4, FT3 and TSH were normal. Anterior neck region ultrasonography showed an enlargement of the left thyroid lobe with poorly defined shapes and inhomogeneous parenchyma while the right lobe of the gland was normal. The 131-I thyroid scan showed a large cold area in the upper part of the left thyroid lobe and preserved radionuclide uptake in the residual parenchyma. The RAIU was normal. We diagnosed acute suppurative thyroiditis and started antibiotics treatment. The day after the patient was still feverish and he gave out from the mouth a great quantity of sero-purulent material with a swelling reduction and improvement of the neck pain. Barium swallow examination did not show any fistula in the cervical esophagus. The fistula opening was demonstrated by indirect laryngoscopy in the postero-lateral side of hypopharynx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298871 TI - [Effect of 5-hydroxytryptophan on the secretion of PRL, GH, TSH and cortisol in obesity]. AB - The role of the neurotransmitter serotonin (SER) in regulating the hypothalamic pituitary function is not completely clarified, although considerable evidence suggests a dominant stimulatory control of ACTH and PRL and a dominant inhibition of TSH, with more variable effects on GH secretion. Furthermore, SER has been implicated in the regulation of appetite, given the anorectic activity of SERergic drugs in animals and humans and experimental evidence suggesting that animal obesity can be a function of SER depletion. In order to study the hypothesized impairment of the SERergic system in human obesity, PRL, GH, TSH and cortisol levels before and after oral administration of the SER precursor 5 hydroxytryptophan (OH-TRY) (500 mg), were determined in 10 obese (BMI 41.5 +/- 1.68 kg/m2) but otherwise healthy women (mean age 50.9 +/- 1.43 yr) and in control group of 7 normal-weight (BMI 20.9 +/- 0.66 kg/m2) women (mean age 49.8 +/- 1.18 yf) after oral administration of the SER precursor 5-hydroxytryptophan (OH-TRY) (500 mg). The results were matched against placebo. In contrast with placebo, OH-TRY administration provoked a PRL and cortisol increase in all the subjects: PRL levels increased in controls at 120 min (p < 0.05) and at 180 min (p < 0.01) and in obese women at 120 and 180 min (p < 0.01); cortisol levels increased in both groups at 90, 120, 180 min (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298873 TI - [Hemolysin from Vibrio cholerae eltor: cloning and expression of genes in Escherichia coli]. AB - A 6.56-kb V. cholerae eltor DNA fragment encoding hemolysin synthesis was cloned in pUC18. The resultant recombinant plasmid pES4H (9.25 kb) was mapped by restriction analysis and shown to express in different E. coli strains as well as in nonhemolytic V. cholerae strains. Application of the cloned fragment as a molecular probe revealed homologous sequences in all V. cholerae strains tested independently on their biotypes, hemolytic activity and presence of vct-genes in their genomes while none of other Vibrio species and related microorganisms contained such sequences. A recombinant E. coli strain, a V. cholerae eltor hemolysin producer, was constructed. The simultaneous expression of hemolytic and toxinogenic properties by the same V. cholerae strains is discussed. PMID- 1298874 TI - [Preparation and regeneration of protoplasts from Bacillus megaterium cells dried by sublimation]. AB - Bacterial protoplasts are widely used in genetical research, for instance, in protoplasts fusion experiments and the transfer of heterologous DNA into bacterial cells. The usage of a new fresh grown culture of bacteria in every experiment restricts the reproducibility of the results preventing the technique becoming widespread. The use of antioxidants as components of stabilizing medium for sublimation drying of Bacillus megaterium cells supported cellular viability in bacterial culture. It also made possible preservation of such cellular fundamental properties as the ability to form protoplasts and regenerate the cell wall. Efficiencies of protoplasts formation and generation are similar for lyophilized and fresh grown cells. Cellular properties are conserved for 6 months of storage at least. Experiments with a lot of lyophilized biomass samples are highly reproducible. The potential of the technique was demonstrated in obtaining the hybrid Bacillus megaterium colonies by fusion of protoplasts derived from lyophilized genetically marked strains stored for up to 6 months. PMID- 1298875 TI - [A highly sensitive non-isotopic system of DNA hybridization using amplification (PCR) for identifying and indicating presence of Brucella]. AB - A non-isotopic amplification system was used to identify and indicate Brucella. The terminal sequences of a protein gene fragment in Brucella outer membrane were identified and direct and reverse primers were chosen for a polymerase chain reaction. (PCR). PCR amplifies a specific DNA fragment, 700 kb in size, only in representatives of the Brucella genus. A probe was design, which is the central part of the amplified DNA fragment, 550 kb in size. Single Brucella cells were detectable with an unlabelled probe in the analyzed samples during hybridization reactions. The system can be recommended for a rapid and reliable analysis in medical and veterinary practice. PMID- 1298877 TI - [Molecular Genetics, Microbiology, and Virusology: an old journal in a new society?]. PMID- 1298876 TI - [pH-dependent fusion of eukaryotic cells, caused by arenaviruses, pathogenic and non-pathogenic for humans]. AB - The conditions necessary for fusion from inside (FFWI) of the BHK-21 cell culture affected by the Lassa and Mopeya arenaviruses were studied. The fusion was shown to occur only in the slightly acid medium and at lower pH meanings for the Mopeya virus, than for the Lassa virus. PMID- 1298878 TI - [Kasugamycin methylase modified by ribosomal RNA from group A streptococci]. AB - Kasugamycin sensitivity in Escherichia coli depends on the specific enzyme methylating rRNA. Native group A streptococci (GAS) were found to be sensitive to kasugamycin. After introduction of the erythromycin gene located on the transposon Tn916E into GAS some of the strains obtained kasugamycin resistance together with erythromycin resistance (erm). One of these strains carrying the transposon in its chromosome was tested for methylase activity. It was demonstrated to be deficient in kasugamycin methylase (ksg). The presented data proves the presence of ksg methylase in GAS. Evolutionary relationship between erm and ksg genes is discussed. PMID- 1298879 TI - [Determination of thermostable and thermolabile enterotoxins in Escherichia coli strains by genetic, biological, and immunoserological methods]. AB - The Escherichia coli strains (75) isolated from patients suffering from diarrhea were screened for ability to produce the temperature-labile or stable toxins (ST or LT) by the different techniques (the hybridization with DNA probes, biological, enzyme immunoassay). The majority of tested strains was shown to harbor the tox-genes controlling the synthesis of ST, LT or both enterotoxins. However, the phenotypic expression of the genes was registered in only some of the strains. The hybridization with the DNA probes is noted to be most perspective in the mass screening of toxigenic strains. The DNA probe used contained the fused estA-eltB genes that makes one able to detect the genes for both enterotoxins. PMID- 1298880 TI - [Search for unique segments of the ectromelia virus genome by cross blot hybridization with DNA from other orthopoxviruses]. AB - In order to identify ectromelia virus (EMV) genome regions which may contain genes responsible for the specific pathogenicity of this virus, blot cross hybridization of EMV DNA with those of other orthopoxviruses was performed. Two hybridization schemes were employed: one of them included hybridization of labelled cloned fragments of EMV with digests of other viral DNAs, the other, reciprocal, consisted in hybridization of labelled total DNAs of various orthopoxviruses with digests of the region of EMV DNA adjacent to the right terminal inverted repeat. It was demonstrated that the counterpart to an approximately 8-kilobase pair portion of EMV genome flanking the inverted repeat could be detected only in the cowpox virus genome but not in the genomes of vaccinia and rabbitpox viruses. XhoI-O and XhoI-K fragments of EMV DNA contained, along with genes found in other poxviruses, certain genes which appeared to be unique for EMV. It is postulated that some of these genes may determine the specific biological properties of EMV, including its pathogenicity for mice. PMID- 1298881 TI - [Cloning the gene for vaccinia virus strain L-IVP growth factor in Escherichia coli]. AB - The growth factor gene of the vaccinia virus LIVP strain has been primarily cloned in a 4.3 kbp long BamHI-EcoRI fragment and then subcloned in a 440 bp fragment. It was shown that clone 4 of the LIVP strain contains a single copy of this gene while the WR strain contains a repeat. The gene is located on a 4.3 kbp BamHI-EcoRI fragment but not on a 2.2 kbp fragment and has four nucleotide changes, three of which result in amino acid substitutions. PMID- 1298882 TI - [DNA probe for detecting Yersinia pestis and serovariant I of Yersinia pseudotuberculosis by detecting specific DNA repeating sequences]. AB - In order to construct a DNA probe for the plague pathogen detection, we have obtained the recombinant plasmid pRD100 carrying an EcoRI-flanked 140 bp fragment from the genetically silent region of Yersinia pestis species-specific plasmid pYP1. When used as a DNA probe for hybridization of DNA from various strains of 25 bacterial species, this DNA fragment was shown to have the complementary sequences in all investigated Yersinia pestis strains (200), including the plasmid pYP1 lacking ones, and in all the studied Yersinia pseudotuberculosis serotype I strains (80). The search for the probe target in these species has led us to conclusion that it is a specific repeated DNA sequence present in more copies in Yersinia pestis than in Yersinia pseudotuberculosis serotype I. The hybridization of these sequences with the radioactive probe and 24 hours autography makes possible the detection of 1.3 x 10(5) cells of Yersinia pestis and 3 x 10(6) cells of Yersinia pseudotuberculosis serotype I immobilized on the nitrocellulose membranes. Use of the probe for analysis of the nitrocellulose membrane fixed spleen smears from animals that died of experimental plague made possible the detection of Yersinia pestis cells within 48 h. PMID- 1298883 TI - [Serovariation of the plague pathogen capsular antigen]. AB - The phenomenon of serovariation in the capsule antigen of the plague pathogen has been found. The synthesis of FI-serovar is determined by the expression of the caf1M gene. The damages in the caf1M gene structure result in production of the FI1 and FI2 serotypes. Expression of the caf1M gene does not affect the secretion of FI-antigen. PMID- 1298884 TI - [Azospirillum brasilense SP245 mutants in production of anthranilic and indolyl-3 acetic acids]. AB - The mutants of Azospirillum brasilense Sp245 altered in the production of anthranilic (Ant) and indolyl-3-acetic (IAA) acids were selected after the chemical or transposon facilitated mutagenesis and divided into the following three classes: Ant+IAA+, Ant+IAA- and Ant-IAA-. A hypothesis on the existence of a pattern for tryptophan conversion to anthranilate that is different from the classic pattern, and on the connection of the indolyl-3-acetic synthesis with this process is suggested. PMID- 1298885 TI - [Change in regulation of influenza virus vRNA synthesis during adaptation to various hosts]. AB - To evaluate the effect of laboratory passaging of influenza virus A/USSR/90/77 (H1N1) on the pattern of vRNA synthesis regulation in course of the one step infection cycle, we have used the viral variants adapted to growth in the continuous cell line MDCK or to the reproduction in the mice lungs in vivo. Enhancement of regulation was registered in the adapted variants as compared to the original virus strain. The results are discussed in connection with possible significance of the vRNA synthesis regulation for the efficiency of viral reproduction under natural conditions or in laboratory passaging. PMID- 1298886 TI - [Plasmid P85 from Azospirillum brasilense SP245: study of the circle of possible hosts and incompatibility with plasmids from Azospirillum brasilense SP7]. AB - The possibility of the stable inheritance of the plasmid p85 mobilized derivatives from Azospirillum brasilense Sp245 in the cells of the bacterial genera Rizobiaceae (Agrobacterium tumfaciens) and Pseudomonadaceae (Pseudomonas putida) has been shown. The plasmid p85 participates in coding for the physiologically active products (the plant hormones). It is not inherited by the Escherichia coli strains. For the first time the incompatibility of azospirillium plasmids has been demonstrated on the example of the plasmid p85 from Azospirillum brasilense Sp245 and the plasmid p115 from Azospirillum brasilense Sp7. PMID- 1298887 TI - HBV risk from fingersticks. PMID- 1298888 TI - Election '92. Nurses in the House? PMID- 1298889 TI - Election '92. Party lines. PMID- 1298890 TI - Election '92. Polls apart. PMID- 1298891 TI - Election '92. Fit for office. PMID- 1298892 TI - Professional development. Have you got a record? PMID- 1298893 TI - Professional development. A personal task. PMID- 1298894 TI - Professional development. Access for all? PMID- 1298895 TI - What price dogs' life? PMID- 1298896 TI - Newly clothed wards. PMID- 1298897 TI - The Gulf War. A gulf apart. PMID- 1298899 TI - Making sense of bone banking. PMID- 1298898 TI - The Gulf War. Bringing back memories. PMID- 1298900 TI - Flowering potential. PMID- 1298901 TI - Blessed reassurance. PMID- 1298902 TI - Cultural variance in health beliefs. PMID- 1298903 TI - Measuring and treating urinary incontinence. PMID- 1298905 TI - Computing in practice. A lesson in reality. PMID- 1298904 TI - Evaluating tympanic membrane thermometry. PMID- 1298906 TI - Journal of infection control nursing. Bad riddance to rubbish. PMID- 1298908 TI - Unconsented HIV tests. PMID- 1298909 TI - Journal of infection control nursing. 'Typhoid Mary'. PMID- 1298907 TI - Journal of infection control nursing. Sharpening awareness. PMID- 1298910 TI - Knowledge and health practices of leprosy patients. PMID- 1298911 TI - Nurses' use of fertility regulating methods--a study. PMID- 1298912 TI - Of lamp lighting ceremony and Florence Nightingale. PMID- 1298914 TI - Substance abuse: the nurse's role in prevention education and caring. PMID- 1298913 TI - Conversion reaction: dynamic formulation and care. A case report and discussion. PMID- 1298915 TI - Relevance of nursing curriculum to 'women health & development'. PMID- 1298916 TI - The revised curriculum of nursing: some problems and challenges. PMID- 1298917 TI - Healthy aging. PMID- 1298918 TI - Problems of communication. PMID- 1298919 TI - Role of nurses in planning new health care projects. PMID- 1298920 TI - World AIDS Day 1992. PMID- 1298921 TI - Eye injuries and foreign bodies. PMID- 1298922 TI - Care of pressure sores in the rehabilitation of paraplegia. PMID- 1298923 TI - Planning nursing education for 2000 AD: in pursuit of reality. PMID- 1298924 TI - A study on IQ. PMID- 1298925 TI - Can nurses strike. PMID- 1298926 TI - [Allergy to beta-lactam antibiotics in childhood. Diagnostic problems]. AB - This study reports about 126 children with an age ranging from 12 months to 12 years having RA to beta-lactamase. More children with an age ranging from 7-12 years (59.5%), and more male (65.9%) than female subjects were studied. 76 patients (60.3%) showed a familial anamnesis of allergic diseases or similar diseases and a personal anamnesis of allergic diseases (45.2%). Among the RA responsible substances the more frequent were semisynthetic penicillin (44.6%) followed by cephalosporin and penicillin. Most clinical manifestations (87.3%) were cutaneous reactions and in smaller number of cases it was possible to observe gastroenteric or respiratory reactions. In 121 patients cutaneous tests were undertaken (Prick tests and intradermoreactions), patch tests, employing: PPL, MDM, Penicillin, Ampicillin, Cephaloridine. 5.8% of the studied subjects showed an allergy. Particularly 2.4% showed a "early" positivity. RAST was carried out in 92 patients and 3 of them showed a positive result (3.2%). This study stresses the opportunity to carry out allergologic tests within 6 months since the beginning of RA. In fact especially in children this test result can soon become negative. Furthermore the reduced percentage of positive allergologic tests can be due to the inclusion in other studies of patients with "coincidental reactions". A certain number of RA can be caused by additive to "per os" products. Finally it will be possible to use "tests dose" even in selectioned cases. These tests can frequently exclude the etiopathogenetic responsibility of beta-lactamic substances. PMID- 1298927 TI - [Role of "leukocyte adhesion molecules" in early periodontal disease]. AB - The purpose of this paper is to focus on functional characteristics of leukocyte adhesion molecules, on their localization and specific ligands. In fact, leukocyte chemotaxis and adhesion to endothelium is an essential step in promoting adequate immune response to bacterial infections. Since periodontal health is highly dependent on neutrophil function against the microbial dental plaque, defects in chemotaxis and adhesion of leukocytes to endothelium often result in severe, early onset periodontitis. Furthermore, oral lesions may be the only clinical manifestation of neutrophil impairment. PMID- 1298928 TI - [Specific IgA against multiple antigens as expression of immunologic deregulation in HIV-positive children]. AB - B-cell dysfunction in HIV-infected children is reflected by hypergammaglobulinemia and high levels of serum IgA. Little is known about antibody specificity since only a small portion of serum IgA appears to be directed against HIV proteins. In the present study the specificity of IgA antibodies against food, inhalant, bacterial and fungi antigens were evaluated in a population of HIV infected children. ELISA method was used for antibody testing. Our results show that in 84.6% of patients IgA against at least one food antigen are present. IgA against inhalant allergens were present in most of HIV infected children but in none of controls. As for anti-tetanus toxoid antigens and anti-fungi antigens, though present in higher percentage in patients, specific IgA were found also in healthy children. If a gastrointestinal dysfunction might be supposed as the cause of presence of anti-food antigen IgA, it is difficult to consider this factor as the cause of presence of specific IgA directed against different antigens. It is possible to postulate that an immunologic dysregulation based on an imbalance between Th1 and Th2 cells or on higher levels of IL-5 and/or IL-6 may lead to a misfunction of B cell and consequently to hypergammaglobulinemia with high IgA levels. PMID- 1298929 TI - [The adolescent celiac]. AB - A group of 81 teenage coeliac patients were recently followed to monitor their compliance with a gluten free diet and also to correlate this with: their general wellbeing, height and weight, antigliadin and antiendomisyal antibody levels and jejunal mucosa patterns. Fifty two patients (64.1%) were on a strict gluten free diet; 18 (22.3%) admitted an occasional gluten intake; 11 (13.6%) were on a normal diet. Symptoms were more frequent in non-compliers that in compliers. There was no appreciable difference between the groups in regard to height and body-mass index, but patients on a normal diet were lighter than the others. Small bowel biopsy was performed on 18 patients with various histological findings. Antigliadin antibodies and antiendomysium antibodies were good indications of a patient's gluten free diet compliance and mucosal damage. PMID- 1298930 TI - [Erratic feeding habits in infants and secondary diseases: findings from a caseload of 440 patients]. AB - The alimentary habits have been analyzed in 440 infant with acute and chronic disease of nutrition. It has been observed a high incidence of dietetic mistakes, whether qualitative or quantitative. These mistakes appeared in correlation with the poor cultural and socio-economic conditions of the population. The Authors compare the observed pathology with the wrong alimentary habits conditioned by low social context and suggest an adequate prophylaxis of infant's nutrition disease, thorough better alimentary habits in childhood and better life conditions of the population. PMID- 1298931 TI - [Lactate dehydrogenase isoenzymes and alveolar inflammation in acute severe bronchiolitis in infants]. AB - The authors have tried to value in 17 children (age: 1-11 months) affected by a severe acute viral bronchiolitis, if the measurement of Lactate Dehydrogenase (LD) isoenzymes could have been used to reveal alveolar injury. In the 76.4% (13/17) of subjects areas of consolidation were demonstrated by chest's radiographic examination due either to atelectasis secondary to obstruction or to inflammation of the alveoli. These coincided with a significant increase respect to a check's group (18 children) of LD4 in 70.5% (12/17), LD3 in 35.2% (6/17) and LD5 in 29.4% (5/17) of children. The presence of an analogous electrophoretic pattern and macrophages degenerated in pulmonary alveolar proteinosis lavage effluent associated with increases in lymphocytes and mononuclear phagocytes in lung specimens from children dead for bronchiolitis help to understand the inflammatory origin of pathological modification of LD isoenzymes observed in this series of cases. PMID- 1298932 TI - [Care of small for gestational age infants: personal caseload]. AB - The Guidelines for Perinatal Care define SGA or IUGR infants those with birthweight < 2500 g and below the tenth percentile for gestational age. In Brindisi's N.I.C.U. in the period from 1/07/1986 to 27/02/1992, 295 newborns were admitted with G.A. = 37.08 +/- 2.87 w (mean +/- s.d.), birthweight = 2013 +/- 505 g, length = 438 +/- 44 mm, head circumference = 307 +/- 31 mm. Among these 80.9% has been discharged in good conditions; 9.4% was discharged with some problems and 9.3% died. In hour Hospital the incidence of SGA at birth has been 1.83% in 1987, 2.13% in 1988, 2.1% in 1990 and 2.3% in 1991, in agreement with the literature's data. In the group of SGA infants, we have had 43.86% with symmetrical IUGR, 39.15% with asymmetrical and 16.98% with intermediate IUGR: In this study, besides, the Authors examine some of the main problems that affected the SGA newborns. PMID- 1298933 TI - [Liver transplant in childhood: our experience]. AB - From december 1984 to december of 1991, 12 children underwent on orthotopic liver transplantation (OLT): 6 had extrahepatic biliary atresia (EHBA), 2 had Byler disease, 2 hepatocellular carcinoma (HCC), 1 Alagille Syndrome and 1 had a hyperacute Wilson disease. The children, transplanted for the most part a broad, return for observation 3 months after OLT. A patient with hyperacute Wilson's Disease had 2 emergency OLTs and died of sepsis (due to Aspergillus); another with EHBA, operated for hepatoportoenterostomy, without result, died after OLT because of a ruptured aortic aneurysm. The other 10 are living with a variable follow-up between 8 months and 7 years. The post-operatory complications were present in 4 cases: in the same patient (15 months old) a hepatic artery thrombosis and then a portal vein thrombosis were observed; 3 patients had to have their biliary-digestive anastomosis redone. 7 of 10 patients had acute rejection. During the first month after OLT infection episodes were mostly due to bacteria (G-), Candida and Pneumocystis carinii (blood and intraabdominal sepsis). In the second period (1-3 months) there were viral infections, in particular CMV. An emergency transplanted patient, incompletely vaccinated, developed HBV infection. During long term follow-up (after the 3rd months from OLT) the children usually have mild infections of the respiratory and urinary tracts. After 1 year, they have a mean annual growth velocity that is between the 50th and 90th percentile. They showed a good rehabilitation. Their hospitalizations rate was reduced if compared with the period before OLT. Health, motor function and general behavior improved significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298934 TI - [Prevalence of heterozygosity for beta-thalassemia among intermediate lower school children in an area of the Venetian lacuna]. AB - This paper reports the results of an epidemiologic survey carried out from 1987 to 1991 among intermediate school students in Chioggia (Venice, Italy) to detect beta-Thalassemia carriers. The screening tests (determination of Mean Corpuscular Volume, Hemoglobin A2) were performed in 3050/4055 (75%) students; the prevalence of carriers was of 3.1%. The results obtained identify this as a risk area for Thalassemia Major and suggest the necessity to adopt prevention measures such as medical information, population screening, genetic counseling and prenatal diagnosis. PMID- 1298935 TI - [Lead concentrations in breast milk of women living in urban areas compared with women living in rural areas]. AB - In the last twenty years a great interest has grown up about the accumulation of lead in the environment, because many studies have found relationship between exposure to low lead doses and neuropsychological impairment of children. The Authors have measured and then compared the lead content of milk from women living in city-areas and women living in rural areas, not having professional lead exposure. 34 samples of women milk from the rural areas and 20 samples from the city areas were examined: the lead mean concentration of the rural areas milk samples was 45.62 microgr/l with a range from 0 to 425 microgr/l; the mean concentration of the city areas samples was 126.55 microgr/l with a range from 1 to 472 microgr/l. The data were compared with the Student t-test and the difference was statistically significant at p = 0.01. The Authors examine the correlations between environmental lead accumulation and increased lead concentration in woman milk, laying stress on the possible hazard to health and neuropsychological development of children, mostly of those living in urban areas with heavy road traffic and industrial activity. PMID- 1298936 TI - [Are metoclopramide dystonias familial?]. AB - Metoclopramide is an antiemetic drug; the effects on CNS (acute dystonic reaction, tardive dyskinesia, parkinsonism) occur in only 1 of 500 patients treated. Acute dystonic reactions are not apparently dose-dependent and suggest individual sensitivity to the drug (idiosyncrasia). We report 4 cases in 2 families (grandmother-grandchild; brother-sister). We feel that, if there is a case of dystonic reaction to metoclopramide, this drug should not be administered to other members of the same family. PMID- 1298937 TI - [Contribution of echography in the diagnosis of gastro-esophageal reflux in children]. AB - 56 children, aged between 0-13 month, affected by chronic vomiting were evaluated both with ultrasound and radiological methods, in a double blind study. 22/56 children resulted to be affected by gastro-oesophageal reflux (GER) with upper GI series versus 18/56 with ultrasound. Four cases, ultrasound negative and X-ray positive, represented a borderline situation in which a mild gastro-oesophageal reflux is to be considered paraphysiological phenomenon. The accuracy and handleness of ultrasound evaluation in GER are emphasized. PMID- 1298938 TI - [Changes in the consciousness state as a symptom of intestinal invagination onset]. AB - Intussusception is the most frequent cause of intestinal occlusion in children aged 3-5 years. Diagnosis is easy to perform in cases with typical clinical presentation. However diagnosis may be difficult in rare cases with atypical symptoms characterized by SNC involvement, that could delay a convenient treatment. We report 4 cases of intussusception presenting initially with consciousness abnormalities, hypotonia and vomiting. In these cases differential diagnosis with other conditions associated with comatose states has to be performed. Some hypothesis may be considered to explain these clinical pictures: 1. increased endorphins excretion during abdominal pain; 2. neurotoxins of bacterial origin released and absorbed by altered bowel; 3. intestinal hormones abnormally produced during the disease. As recommended by Rachmel, the condition should be suspected in all children presenting with the association of vomiting and lethargy and a radiological or tomographic study of abdomen should be performed also in cases without intussusception typical symptoms. PMID- 1298939 TI - [Reproducibility of pediatric information collected with various methods: postal/telephone questionnaire and direct interview]. AB - The paper reports on a research aimed to evaluate the repeatability of some paediatric data obtained from the parents by using different collection instruments: telephone interview, mail questionnaire, in-person interview. The study included 699 children consecutively born in the Policlinico Universitario "A. Gemelli" from September to November 1983. After 3 years a questionnaire containing questions about measles, anti measles immunization, age at which the baby started to walk, disease delaying the walking, and orthopaedic examinations was sent by mail to 149 families; the other 550 families were searched for by telephone and, if found, asked the same questions. All the contacted families were invited for a paediatric check-up, during which the same data were collected through direct interview. For each question crude agreement and K statistic (which controls for the agreement attributable to chance) were computed with respect to both the phone/direct and mail direct comparisons. 391 families (56%) were traced for the first interview, due to the high number of them which had moved home. Among these 289 (74%) attended the paediatric check-up. On the whole, rather high values of K statistic were observed, ranging from 0.59 (question on diseases delaying the walking, comparison phone/direct) to 0.93 (question on anti measles immunization, comparison mail/direct). Due to the small sample size, the estimates concerning the comparison mail/direct are rather imprecise. Although its potential is limited by the low response rate, the study brings good evidence that the information considered is not sufficiently reliable when reported retrospectively by parents. However, the keeping of a prospective individual record containing data of medical interest should be encouraged. PMID- 1298940 TI - [Indications for therapy of labial frenum]. AB - Reporting some cases and literature researches, the Authors point out the indications of labial frenum therapy. The results show no correlations between teeth diastema and frenum: surgical therapy of frenum is recommended after complete eruption of permanent teeth. The correct surgical procedure must be radical and conducted in a short time: frenectomy prolonged to the incisive papilla, is recommended. PMID- 1298941 TI - [Short lingual frenum: clinical and therapeutic considerations]. AB - The Authors report researches on the tongue embryology. Real indications of the surgical therapy of tongue-tie are discussed, considering a wide population of 8 age children examined. PMID- 1298942 TI - [Rett's syndrome: description of a case with abnormal respiratory pattern]. AB - Rett' syndrome is a progressive disorder that occurs in females and is characterized by autistic behavior, dementia, ataxia, loss of purposeful use of the hands, and seizures. Patients with Rett' syndrome have been observed to have stereotyped hand movements (hand-washing) and to exhibit intermittent hyperventilation. To characterize more precisely the respiratory pattern associated with this disorder, SAO2 and pH studies were made during sleep and wakefulness in a girl with this syndrome. These studies showed abnormal respiratory pattern during wakefulness characterized by hyperventilation periods (SAO2 98%, alkalosis) and ipo-apnea (SAO2 80%); during the sleep, ventilation became regular (SAO2 94-96%). The occurrence of disorganized breathing and compensatory hyperpnea during wakefulness with regular, continuous breathing during sleep suggests an altered or impaired voluntary/behavioral respiratory control system. PMID- 1298943 TI - [True hermaphroditism: description of a case]. AB - An infant with normal male external genitalia and preoperative diagnosis of right hydrocele and left cryptorchidism got operative diagnosis of true hermaphroditism. Left ovary and Fallopian tube were removed. Karyotype was 46.XX/47.XXY. The results of the genetic study are shown. PMID- 1298944 TI - [Neonatal hyperthyroidism. A clinical contribution]. AB - A case of female child who had transient signs of hyperthyroidism after the birth is presented. Authors describe the clinical course and discuss the possible pathogenetic mechanisms. The importance of a timely diagnosis, a correct therapy and follow-up is emphasized. PMID- 1298946 TI - Current perspectives: cardiovascular nutrition education. Introduction. PMID- 1298945 TI - Lose weight and win: a church-based weight loss program for blood pressure control among black women. AB - The Baltimore Church High Blood Pressure Program (CHBPP) offers a behaviorally oriented weight control program consisting of eight weekly 2-h diet counseling/exercise sessions. Pre- and post-program weight and blood pressure measurements were analyzed for 184 black and 3 white women aged 18-81 years (mean 51) who participated in the program in 1984-1986: 88 were taking antihypertensive medication (Rx) and 99 were not (no Rx). Mean weight loss was 6 lb in both groups: -18 to +7 lb in the Rx group and -31 to +3 lb in the no Rx group. The mean systolic/diastolic blood pressure (SBP/DBP) decrease was 10/6 mmHg in the Rx group and 5/3 mmHg in the no Rx group (P < 0.001 for all pre/post comparisons). Final SBP was < 140 mmHg for 74% of participants, versus 52% initially. Final DBP was < 90 mmHg in 92% versus 65% initially. Supporting the inference that BP decreases among weight control program participants reflect program effects, percent changes in SBP and DBP (week 2 to week 8) were significantly correlated with percent change in weight (rs = 0.23-0.36; P < 0.05). Comparison data for 25 women from the CHBPP population showed a mean SBP/DBP increase of 8/2 mmHg over an 8-week interval. Based on follow up measurements 6 months after the end of the 8-week program for 74 of the 187 women, weight lost during the 8-week program was maintained or exceeded by 65%. Net weight change at 8 months from baseline for women in the follow up subsample ranged from -28 to +4 lb; mean (SD) -6 (7) lb. Weight loss and related dietary or behavioral changes resulting from participation in a weight control program can enhance blood pressure control among black women. PMID- 1298947 TI - Characteristics associated with compliance to cholesterol lowering eating patterns. AB - The achievement of high levels of adherence is the most important objective of nutrition intervention programs. In order to determine characteristics which were most highly related to adherence to a cholesterol lowering eating pattern, a group of 264 men were sampled. Participants had been enrolled for six years in a multi-risk reduction program for cardiovascular disease which included dietary intervention for blood cholesterol. They were asked to respond to 35 statements, each of which was designed to reflect one of seven characteristics: perception of threat of disease, cost-benefit of therapy, quality of care, social support, external environmental media, and internal as well as external health locus of control. There were seven possible responses to each statement, from strongly agree to strongly disagree. Using a reduced rank regression analysis the numerical answers to the items were treated as a set of predictors for the criterion measure, the food record rating (FRR) score which reflected compliance to a cholesterol lowering eating pattern. Overall the seven characteristics accounted for almost half of the variance in the FRR score (multiple R = 0.48). The most highly related characteristics were cost-benefit, quality of care and external environmental media. These results are highly consistent with those obtained in another population, and indicate the importance of minimizing the cost and increasing the benefits of cholesterol lowering programs by providing high quality treatment programs which emphasize tailoring the regimen to the individual. These results also support the importance of public information efforts such as the National Cholesterol Education Program. PMID- 1298948 TI - A systematic approach to educating elderly patients about their medications. AB - The purpose of this study was to evaluate a pharmacist-initiated, total package, patient education program based on the concepts described in the PRECEDE model. This program was directed towards 94 therapeutically complex elderly patients and consisted of a medication history, therapeutic evaluation, patient education needs assessment, patient education session, and a patient feedback/satisfaction telephone interview. Pharmacists identified on average 5.6 medication-related problems and provided an average of 6.2 recommendations. Problems commonly identified involved inadequate drug knowledge (25.5%), noncompliance (22.7%), and inappropriate drug use (17.4%). Typical recommendations included altering drug use (35.9%), improving compliance behavior (18.1%), and improving communication with health professionals (18.1%). Patient satisfaction with the education session was overwhelmingly positive. Based on the findings of this study, it is apparent that a patient education program based on the PRECEDE model can be used successfully by pharmacists to prepare education plans that would benefit the therapeutically complex elderly patient. PMID- 1298949 TI - Nutrition education for cardiovascular disease prevention among low income populations--description and pilot evaluation of a physician-based model. AB - Low income Americans are at greatest risk for coronary heart disease but have least access to health promotion programs for life style modification. Primary care physicians may represent one of the few sources of preventive care available to the poor. However, the majority of physicians feel unprepared to help patients achieve dietary change, and few existing nutrition intervention programs address the special needs of low literacy populations. The Food for Heart Program was developed to facilitate dietary counseling experienced by primary care physicians who care for low literacy patients and to overcome barriers to behavior change faced by patients. The program consists of three components: (1) a validated dietary risk assessment that rapidly identifies atherogenic eating habits and requires no nutritional expertise to administer or interpret, (2) a structured diet treatment program that is culturally specific for a southern patient population and links practical behavior change recommendations with results of the diet assessment, and (3) a system for monitoring and reinforcement that prompts physicians to review progress, reinforce prior messages, and reward positive change. Behavior change theory is used to guide the intervention and readability of the material has been assessed at the 5-6th grade level. An evaluation study of the Food for Heart Program suggests that it has a positive impact on physician counseling and that patients are responding favorably to these efforts. PMID- 1298950 TI - Improving self-care among older patients with type II diabetes: the "Sixty Something..." Study. AB - A 10-session, self-management training program was designed specifically for persons over 60 years of age having Type II diabetes. It targeted social learning variables, especially problem-solving skills and self-efficacy, found to be related to diabetes self-care in earlier correlational research. One hundred two adults were randomized to immediate or delayed intervention conditions. At posttest, subjects in the immediate intervention condition showed significantly greater reductions in caloric intake and percent of calories from fat than control subjects. The intervention also produced greater weight reductions and increases in the frequency of glucose testing than did the control condition. Improvements among immediate intervention subjects were generally maintained at a 6-month follow-up. Intervention results from subjects receiving delayed intervention closely replicated those for immediate intervention subjects. We conclude that a relatively short-term program can improve self-management skills of older diabetic adults, and that there is an important need for such interventions. PMID- 1298951 TI - Assessment of the patient-doctor interaction scale for measuring patient satisfaction. AB - This study assessed the validity, reliability and usability of the Patient-Doctor Interaction Scale (PDIS) in a university-based family practice center. Health maintenance visits and problem visits were included, and data were collected at the time of the visit and again 1 month later. Three different methods of administration (in-person, telephone, and mail) were used to assess usability. Of 91 patients approached, 1 refused to participate. A total of 64 (70%) patients completed the instrument adequately to permit analysis. PDIS scores correlated with overall assessment of patient satisfaction (P < 0.01), suggesting criterion based validity. Internal consistency (reliability) of the PDIS was indicated by Cronbach's alpha which were consistently greater than 0.80. Scores and return rates varied by method of administration, with the telephone method performing best. The PDIS appears to fulfill the requirements for a valid, reliable and useful instrument to assess patient satisfaction in family practice settings. PMID- 1298952 TI - A computerized cancer information system. AB - Cancer information was made available via a computer to patients visiting the University of Connecticut Dental Clinics. The computer program was menu driven. An option allowed users to leave messages for the system owners. The computer program generated a log of usage, user comments and items chosen. The user could choose from the following topics: (1) general information on cancer; (2) diet, nutrition and cancer; (3) smoking; (4) the environment, occupations and cancer; and (5) physical checkups. An option to leave a message for the system operators was the option chosen least. Analysis of the usage log shows that the system was used substantially while people were waiting in the clinic and that at least three or four individuals used the system every clinic day. Such information systems can provide important information to the public. The novelty of the system and the lack of supervision did not deter public use. PMID- 1298953 TI - Child passenger restraint use and motor-vehicle-related fatalities among children -United States, 1982-1990. PMID- 1298954 TI - [The role of prolactin in neoplastic disease]. AB - The role of prolactin in carcinogenesis in experimental animals and in humans presented. PMID- 1298956 TI - [Perspectives in the use of cytokines for treatment of neoplasms in children]. AB - This review summarizes the experience with growth factors that have been tested and that currently are being introduced in clinical trials. In addition, author discusses some factors with possible future interest for clinicians. PMID- 1298955 TI - [2-Acetylaminofluorene--a model mutagen and hepatocarcinogen. Characterization of its interactions with DNA]. AB - 2-Aminofluorene and its derivative 2-acetylaminofluorene are well known mutagens and carcinogens. Molecular mechanisms concerning their mutagenic and cancer promotion activity during hepatocarcinogenesis are summarized in the paper. PMID- 1298957 TI - [Recent views on the role of nerve growth factor and other molecules with well documented neuronotrophic action]. AB - In the present paper recent data of the structure, regulation of production and mechanisms of action of the nerve growth factor and other proteins of well documented neurotrophic influence were reviewed. The purpose of this article was also to discuss the possible role of these molecules in the pathogenesis of some neurological diseases and their potential therapeutic importance. PMID- 1298958 TI - [Muroctasin, a muramyl dipeptide derivative]. AB - This paper presents a review of studies on the metabolism, pharmacological and clinical properties of a new synthetic muramyl dipeptide derivative N2-/(N acetylmuramoyl)-L-alanyl-D-isoglutaminyl/-N6-stearoyl-L-lysine(MD P- Lys(L18), muroctasin). Due to its effect on the number of peripheral blood leukocytes this compound is expected to be a useful drug for the treatment of leukopenia induced by cancer chemotherapy or radiation therapy. PMID- 1298959 TI - [Polymorphism of acetylation and oxidation phenotypes and the risk of neoplasms- pharmacogenetic approach to the epidemiology of neoplasms]. AB - In recent years more and more attention has been devoted to the relation between the appearance of neoplasms and the polymorphism of the acetylation and oxidation phenotypes. The work is an attempt at presenting modern views and statements on that subject. PMID- 1298960 TI - [Pharmacokinetics of sulphonamides administered in combination with trimethoprim]. AB - Pharmacokinetic properties of sulfametrole, sulfamoxole, sulphamerazine, sulphadiazine, sulphamethoxazole and sulfamethopyrazine, i.e. the sulphonamides administered in combination with trimethoprim have been compared. From the pharmacokinetic point of view sulphadiazine seems to be the most optimal sulphonamide to apply jointly with trimethoprim. Some of long-acting sulphonamides like sulfamethopyrazine and sulfadimethoxine, used as components of above mentioned combinations, possess comparable clinical efficacy in spite of differences of their and trimethoprim half-lives. PMID- 1298961 TI - Oral mucosal changes related to plasma ascorbic acid levels. AB - The role of vitamin C in maintaining mucosal health is poorly documented. The purpose of this study was to examine the presence of oral mucosal lesions in subjects with low ascorbic acid (AA) levels in plasma. AA plasma levels of 843 working elderly people in six rural villages in Eastern Finland were determined. All subjects with low plasma AA levels (< or = 25 mumol/l) (n = 106) formed the study group. Controls with normal AA levels (> or = 50 mumol/l) (n = 103) were drawn from the same population. They were matched for age, sex and number of teeth. Oral mucosal lesions in all subjects were recorded clinically using a double-blind method in all subjects. Petechias, leukoplakia and lichenoid lesions were the commonest lesions of the oral mucosa. Only in leukoplakia there was a statistically significant difference between the groups (p < 0.01). Smokers had more leukoplakia than non-smokers. The prevalence of leukoplakia was higher when smoking was combined with AA deficiency. PMID- 1298962 TI - Use of dental services by students of Helsinki University during six years. AB - This follow-up study was carried out to survey the utilization of dental services among university students, together with treatment modalities received during their six years of university studies. Initially 20-year-old students were followed during six years, starting from their first year at the University of Helsinki. Results of the questionnaire showed that during the previous 12 months 59% of the students had had a dental appointment, mostly on their own initiative. According to the patient register, 83% of the students, during their studies, had received dental care financially subsidized at the Finnish Student Health Service (FSHS) in Helsinki. During the six years of follow-up, the mean number of appointments was 9.3 per patient (SD 6.8). Female students made dental appointments relatively more often than did male students (p < 0.01). The main treatment modality was restorative care. Patients did not show up for 3.5% of all appointments reserved. One sixth of all visits were made by a group representing 5% of the study group. In conclusion, as the utilization of FSHS dental services was very common, and as restorative dentistry continues to be the main treatment modality among Finnish university students, prophylaxis of caries in systematic dental health care programmes at FSHS is of prime importance and thus has a good possibility to reach each student. PMID- 1298963 TI - Health habits in a Finnish village. AB - This study is part of a collaborative study entitled "Life-style and health" which is being conducted in Finland, India and Tanzania, using the same methods. The aim of the study is to describe health habits (smoking, alcohol consumption, use of medical drugs, exposure to sugars and hygiene habits) in Viekijarvi, a village in eastern Finland. Of the villagers 50% of those aged 20 years and over were randomly selected to take part in the study. Of these, 72% (n = 179) returned the standard questionnaire they had been sent. Smoking was as common among men in Viekijarvi as in Finland in general, but less common among women. Alcohol consumption reflected the national consumption. The use of medical drugs was high: 45% of respondents used such preparations daily. The most common exposure to sugar on a daily basis was sugar-sweetened coffee. Most people in Viekijarvi (89%) brushed their teeth at least once a day. A strong positive correlation was found between frequencies of toothbrushing and handwashing mirroring unidimensional hygienic behaviour. The results of this study will form a basis for a health promotion programme, to be developed by the villagers themselves. PMID- 1298964 TI - Tooth cleaning methods and their effectiveness among adults in rural Tanzania. AB - This study was undertaken to investigate how various population characteristics affect the choice of different tooth cleaning methods and to estimate their role in preventing occurrence of plaque, calculus and gingivitis among rural adults in Tanzania. Two hundred adults aged 20 years and over were interviewed and clinically examined for plaque, calculus and gingival bleeding. A high proportion (97.5%) of the subjects reported that they clean their teeth every day. Among them, 69.4% used only indigenous tooth cleaning methods, 16.3% only factory made toothbrushes and 14.3% both. Twigs (Chewing sticks) were the most commonly used indigenous tooth cleaning method, followed by charcoal. Together with age, educational and occupational status and tribal origin significantly affected the choice of tooth cleaning method. Men had more often visible plaque than women (OR = 2.84). However, other sociodemographic factors and the method of cleaning teeth were not significantly associated with the occurrence of plaque, calculus or gingival bleeding. PMID- 1298966 TI - Dental caries in the future: a global view. AB - Although the prevalence of caries has decreased markedly in children, adolescents, and young adults in most industrialized countries, caries continues to be the main reason for tooth loss, particularly among the high risk segment of the population. In many developing countries, where traditional dietary patterns have changed to include sugar-containing foods and beverages, caries prevalence has increased and will continue to do so in the immediate future. Accordingly, it would be a serious mistake to be complacent about caries prevention. In future industrialized countries will see computers playing a significant role in cariology, finding applications not only in research and practice administration but directly in clinical practice as well. They will be used in every operatory in the assessment of caries risk, the recording of caries prevalence, the direct storing of radiographic information, and the restoration of carious teeth, assisted by computer-aided design and computer-aided manufacture (CAD/CAM) technology. Fluoride therapy, both systemic and topical, will continue to be the basis of caries prevention. Dental sealants, which are highly effective in protecting pits and fissures when applied soon after the teeth erupt, will be more widely used in the future when insurance plans will pay for prevention. Substitution of sucrose and syrups by non-fermentable sweetening agents can also reduce caries increments, but most agents are more expensive than sucrose and require consumer education to pay for the additional cost. Caries, as an infectious and transmissible disease, is amenable to prevention by interfering with the chain of transmission or by suppressing the putative pathogens, the mutans streptococci, in infected patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298965 TI - Chlorhexidine solutions, gels and varnishes in caries prevention. AB - To combat dental caries, a chemical has been sought that possesses stronger antimicrobial properties than fluoride in support of its physicochemical tooth protecting properties. These searches have led to several agents, of which chlorhexidine (CH) appears most effective. To reduce local side effects of the well-known 0.2% CH mouthwash, a 0.05% CH gluconate + 0.04% NaF solution, pH 5.9, has been developed. Use of this combination over a 2-year period resulted in a 53% reduction in caries increment and a 75% reduction in gingival bleeding, i.e. a clear duality of prevention of oral disease (Luoma et al. 1978). Staining of teeth was minimal and easily removable in about one third of the subjects. To lessen the contribution of patients, chlorhexidine gels, without but more especially with fluoride have been professionally administered. Reductions in salivary mutans streptococci after short periods of gel applications have been found to persist longer than reductions after brief periods of mouthwashing. Reductions of approximal caries increment by about 50% in children, and root surface caries in adults have been obtained through use of CH gels. The effect on root surface caries in adults was equal to that obtained through use of local fluoride applications. Dental CH varnish seems promising, especially because a very short contact time with a tooth may be sufficient to reduce mutans streptococci. No simultaneous effects against caries and gingivitis of CH gels or varnishes has been reported. Comparisons of CH solutions, gels and varnishes, with or without fluoride, in relation to their potentials for preventing oral disease in subjects at risk remain to be accomplished. PMID- 1298967 TI - Craniofacial developmental biology--an expanding field of dental research. PMID- 1298968 TI - Pharmacological treatment of intermittent claudication: double blind controlled study of Sulodexide vs placebo. AB - A double blind placebo controlled randomized study was used to assess the clinical variations caused by Sulodexide treatment (100 mg/die) vs placebo in 30 patients with a mean age of 50.3 years suffering from peripheral arterial obstructive disease of the lower limbs (II stage). The general tolerance of the therapy was monitored over the medium-term. There were marked changes in the clinical signs and symptoms in the Sulodexide group, which showed a gradual constant improvement, while they were stationary in the placebo group. Confirmation of the marked improvement in the Sulodexide group was provided by the Winsor index which showed a significant increase in these patients while only a minimum variation was observed in the placebo group. The positive antithrombotic action of the active treatment led to an increase in the blood supply in previously ischemic regions, without creating haemorrhagic risks or disturbing the haemostatic balance. The absence of adverse reactions and good systemic tolerance is also noteworthy. PMID- 1298969 TI - [Hydatid choleperitoneum: a rare complication of hepatic hydatid disease]. AB - The authors report their experience relative to hydatid choleperitoneum which is a rare complication of hydatid hepatic disease (one case of 236 operated). They underline how such pathology constitutes a clinic and anatomopathological case, well characterized and different from those offered by other complications of this hepatic disease. They draw attention moreover on how preoperative diagnosis is often difficult and consequently how the surgical therapeutic technique requires a very careful examination of anatomic relations of the lesion and recognize, as a chiefly foundation, a radical treatment of hepatic disease and whenever possible, the removal of the pseudomembrane of encystment. PMID- 1298970 TI - Adenocarcinoma and epidermoid carcinoma of the lung in the elderly. AB - Primary lung carcinoma, in the elderly, presents some interesting epidemiologic and clinical characteristics. The authors, after reviewing the international literature, stress the differences of behavior and incidence of epidermoid carcinoma and adenocarcinoma occurring in elderly patients as compared to those found in younger patients. They report their experience which is similar to that reported in the medical literature. PMID- 1298971 TI - [A geriatric case of colonic angiodysplasia]. AB - A case of colic angiodysplasia in an elderly patient affected by chronic renal failure is discussed. Different methods suitable for management of these vascular ectasies are briefly reported. Prominent role of colonoscopy in the diagnosis of such disease is emphasized. PMID- 1298972 TI - [Venous bypass for treatment of chronic obstructive venous insufficiency of lower limbs]. AB - About 1 to 5 percent of patients affected by chronic obstructive venous disease of the lower extremity, are eligible to surgical treatment, by veno-venous bypass, for the relief of unerely invalidating symptoms. Indications to operation include a class II to III chronic venous insufficiency of the deep venous system, failure of medical treatment continued for at least 12 months, good patency of outflow axis, a significant gradient of pressure between discared and outflow axis, a good quality saphenous vein to be utilized for bypass. The case of an aged patient, successfully treated with a femoro-femoral venous bypass, associating an artero venous fistula, is presented and indications to the operation in the older patients, together with indication to and technical details of performing the fistula are discussed. PMID- 1298973 TI - [Evaluation of protein compliance in patients with chronic renal insufficiency undergoing hemodialysis treatment]. AB - The majority of hemodialyzed patients manifests a proteic malnutrition. This metabolic status is a main factor in the morbidity and mortality of such subjects. It is therefore necessary to dispose of more adequate diagnostic instrumentation to offset this highly invalidating condition. The ongoing and severe evaluation of the nutritional status by means of up-to-date and sophisticated techniques such as antroproteic parameters may contribute to the maintenance of good conditions while refraining the evolution of various and often lethal complications induced by chronic renal failure. PMID- 1298974 TI - [Early gastric cancer. Clinical contribution]. AB - The authors report their experience on 37 cases of Early Gastric Cancer on 1978 1990 period. They underline the excellent results obtained with subtotal gastrectomy and lynphectomy without deaths neither returns. They stress the diagnostic precision of endoscopic exam now of first choice in the early diagnosis of Early Gastric Cancer. PMID- 1298975 TI - [Colorectal carcinoma: our experience]. AB - The authors report their experience for 158 cases of colon rectum cancer, surgically treated on surgical department of USL 1 Marche. Evaluated short term and long term results they conclude that the only possibility to improve presently the survival of this disease resides on early diagnosis depending to secondary prevention programs. PMID- 1298976 TI - [Primary carcinoma of the gallbladder. Our experience]. AB - The authors focus on some aspects of gallbladder primitive cancer and report their experience about 14 cases. They confirm the malignancy of the disease and the severe prognosis due to diagnostic delay. Only the mucosal localization may be radically treated even by simple cholecystectomy. PMID- 1298977 TI - [Current status of diagnostic imaging]. AB - The authors overview the diagnostic progresses as based on the state of art of imaging which evolves at an electrifying and committing pace towards of a broader horizon of medical fields. They aim at creating centralized integrated diagnostic units in hospitals and at promoting physicians, and technicians skills. PMID- 1298978 TI - [Cultured human skin: prospects for use in the treatment of local burn injuries]. PMID- 1298979 TI - [Eosinophils and asthma]. AB - There has been continuing debate concerning the precise role of eosinophils. They appear to be an integral component in the pathogenesis of asthma, albeit their role has not as yet fully delineated. PMID- 1298980 TI - The problem of thalassemia in Thailand. AB - About one per cent of the Thai population are affected with thalassemic diseases. In each year there are almost 50,000 pregnancies at risk of having an affected fetus, one fourth of which result in thalassemic newborns. Both alpha- and beta thalassemia, including hemoglobins E and Constant Spring, are common in Thailand. Their distribution varies from region to region and among different ethnic groups. About 30-40% of the population are carriers of at least one of the abnormal genes. Thalassemias and hemoglobinopathies are common and heterogeneous in Thailand. They combine to give more than 60 thalassemic syndromes with varying clinical severity. Abnormalities can be detected in every organ system. Studies in detail into each clinical problem will lead to better management. Hematological and molecular studies on different types of thalassemia in Thailand have made it possible to give prenatal diagnosis service to those pregnancies at risk of having a thalassemic child. Sporadic services have been given in three centers. Systematic prevention and control program is being planned by the cooperation of both the public and private sectors. PMID- 1298981 TI - Interaction between endothelial cells and thalassemic red cells in vitro. AB - Erythrocytes from 45 patients with thalassemia and/or hemoglobinopathies were studied for their cytoadherence property to the vascular endothelial cells in vitro. In plasma free medium, erythrocytes from patients with beta-thal/Hb E both splenectomized and nonsplenectomized, HbH diseases (alpha-thal 1/alpha-thal 2 and alpha-thal 1/Hb Constant Spring genotypes) and homozygous Hb E subjects bind to endothelial cells at a greater number as compared to the binding cell number of normal erythrocytes (p-value < 0.05 in all types). Addition of autologous platelet-rich plasma or whole blood to the culture system causes further increase in the number of adhering beta-thalassemia red cells. Platelet-rich plasma had more enhancement effect than the whole blood. However, no such enhancement of both platelet-rich plasma and whole blood was demonstrated in the culture of normal or alpha-thalassemia erythrocytes. Increased binding between red cells and endothelial cells may contribute to the greater risk of vascular occlusion in thalassemic patients. PMID- 1298982 TI - Thalassemic serum impairs endothelial cell growth in vitro. AB - Endothelial cells cultured for 3 days in the presence of hemoglobin H pooled sera had significantly decreased cell proliferation compared to those in normal serum. Inhibition was demonstrated at a concentration of 20% pooled serum in the cultured medium. Further decrease was shown in the presence of 30% pooled hemoglobin H sera. Sera from two genotypes of Hb H disease (alpha-thal 1/alpha thal 2 and alpha-thal 1/Hb Constant Spring) had the same degree of inhibitory effect. Pooled sera from beta-thal/Hb E patients (both splenectomized or nonsplenectomized cases) had no such inhibitory effect. However, at day 4 and 5, the growth pattern relatively declined. Bilirubin at a concentration greater than 4.0 mg% in the medium 199 also caused significant decrease in cell proliferation. Since the diluted Hb H serum had bilirubin less than 4.0 mg%, the inhibitory effect of the pooled HbH serum is thus not due to effect of bilirubin. The difference between HbH and beta-thal/HbE sera in terms of inhibition of endothelial cell proliferation is the new finding that needs further investigation to explain vascularization and hemostasis in the patients of these two genotypes. PMID- 1298983 TI - Liver tissue injury secondary to iron overload in beta-thalassemia/hemoglobin E disease. AB - Liver tissues from 17 patients with advanced stages of beta-thal/Hb E disease were examined by light and electron microscopy, with emphasis on cellular damage due to excess iron overload. Various histochemical stains were performed to grade degrees of iron deposition and fibrosis, and to demonstrate hepatitis B surface antigen, in Kupffer cells as well as macrophages. The results of light and electron microscopic studies were correlated. There was a variation in the distribution of hepatic iron and the severity of fibrosis. In most of the cases ballooning degeneration of the hepatocytes, increase in number of lysosomes, hemosiderin and ferritin in hepatocytes as well as in the sinusoidal lining cells were found. The ferro-acidophilic body, representing another important form of hepatocellular necrosis also occurred. So far no precise mechanisms can be concluded. PMID- 1298984 TI - Brain pathology in 6 fatal cases of post-transfusion hypertension, convulsion and cerebral hemorrhage syndrome. AB - Six fatal cases of post-transfusion hypertension, convulsions and cerebral hemorrhage syndrome were found in a series of 76 autopsies of thalassemic patients. Five of these cases were hypertensive. At autopsy the brains were all markedly edematous and congested. Visible cerebral hemorrhages were found in 3 patients. Microscopically all cases showed small focal or perivascular hemorrhages and 1 patient had extensive arterial type hemorrhage. Microdissecting aneurysms characteristic of hypertensive cerebral hemorrhage were found in two. No underlying vascular disease was found in these 6 patients. A correlation was attempted between possible causes of post-transfusion hypertension and convulsions and anatomical findings. PMID- 1298986 TI - Novel thrombolytic therapy discovered from traditional oriental medicine using the earthworm. AB - Since a few thousand years ago, the earthworm has been used as a drug for various diseases in China and the Far East. However, modern scientific pharmacological studies have not so far been performed. We extracted a very strong fibrinolytic enzyme from the earthworm, Lumbricus rubellus. This enzyme was heat-stable and displayed a very broad optimal pH range. Purification of the enzyme was performed and three partially purified fractions were obtained. These three fractions were further subdivided, and six purified fractions (F-I-0, 1, 2, F-II, and F-III-1,2) were finally obtained. Based on results of their enzymatic activities against various substrates, the fraction I enzymes are thought to represent chymotrypsin like enzymes and the fraction III enzymes to represent trypsin-like enzymes. The fraction II enzyme appears to be neither a trypsin-nor chymotrypsin-like enzyme nor an elastase. We therefore designed trials for in vivo experiments on human volunteers. 120 mg of lyophilized earthworm powder was administered orally to 7 healthy volunteers (aged 28-52 years old) three times after meals every day for 17 days. Blood was withdrawn once a day before and at 1, 2, 3, 8, 11 and 17 days after commencing the administration. The fibrin degradation products (FDP) value, tissue plasminogen activator (t-PA) antigen level and t-PA activities were measured in the blood. Before the administration, the t-PA antigen level was 5.6 +/- 0.38 ng/ml, and it gradually increased until the 17th day. The FDP level was increased on the 1st and 2nd day after the administration, but had decreased and normalized by the 17th day. The fibrinolytic activities also tended to show an increase during the experiment. These results suggest that earthworm powder represents a possible oral thrombolytic agent. The earthworm enzyme may thus be applicable for treating patients with thalassemia. PMID- 1298985 TI - Cytoprotective effect of dilazep on hydrogen peroxide-perturbed vascular endothelial cells. AB - The effect of dilazep and dimethyl thiourea (DMTU) on the hydrogen peroxide derived injury of culture pulmonary artery epithelial cells (CPAEC) was assessed by colorimetric assay of MTT formazan (MTT formazan assay). When CPAEC were treated with hydrogen peroxide, neither cell lysis nor detachment of the cells from surface of the well was observed. However, the MTT formazan formation was decreased in a time and dose dependent manner. The decrease in the formation was significantly suppressed in the presence of dilazep (0.1 to 10 microM) or DMTU (0.01 to 0.3 microM). CPAEC treated with hydrogen peroxide in the same way enhanced an activation of prothrombin, and this enhancement was significantly inhibited in the presence of dilazep (1 to 3 microM). These data indicate that dilazep exerts a cytoprotective effect against challenges of intracellular oxidant produced by hydrogen peroxide and suppresses augmented procoagulant activity of injured cells. PMID- 1298987 TI - Hypoxemia in thalassemia. AB - Data are reviewed describing hypoxemia, a newly identified feature in thalassemia. Evidence indicates platelet aggregation in the pulmonary circulation as being a key factor leading to hypoxemia and cor-pulmonale with right heart failure. PMID- 1298988 TI - Pulmonary thromboembolism in thalassemic patients. AB - Chronic pulmonary thromboembolism plays an important role in cardiac failure which is a major cause of death in thalassemic patients over 20 years of age. This report is a study of autopsy lung tissue from 58 patients with beta thalassemia/hemoglobin E disease (beta-thal/HbE), including whole lungs from five, 13 patients with hemoglobin H disease (HbH), and eight patients with beta thalassemia major (beta-thal) including whole lung from one. Pulmonary thromboembolic lesions were found in 24 of 58 (41%) patients with beta-thal/HbE, of which 21 of 39 (54%) were splenectomized patients and 3 of 19 (16%) were nonsplenectomized patients, with the incidence increasing with age. Lung maps showed the greatest number of lesions in the lingula, right middle lobe, and anterior segments of both upper lobes. Pulmonary thromboembolic lesions were also found in one of 13 HbH patients and one of 8 beta-thal patients, both splenectomized. Eight of the 27 patients with these lesions had right ventricular and 14 biventricular hypertrophy, reflecting the deleterious effect of such lesions. Possible causative factors are discussed. PMID- 1298989 TI - Pulmonary microthromboemboli in thalassemic cases. AB - Lung specimens obtained from wet materials were reviewed for detection of microthrombi. Multiple microthrombi, which were composed mainly of platelets, were seen in the pulmonary arteriole and microcirculation in two autopsy cases with splenectomized thalassemic disease. These findings provide a rational explanation for the increased spontaneous platelet aggregation in the whole blood, and may be an additional factor to the progress of pulmonary dysfunction and hypoxemia seen in splenectomized thalassemic patients. PMID- 1298990 TI - Pathogenesis of hypoxemia. AB - Thrombocytosis and morphological changes in shape and size of circulating platelets are commonly found in splenectomized thalassemia patients. Functional abnormalities of the platelets are evidently related to their fragile nature. Spontaneous aggregation of platelets can easily occur following application of mild pressure either from a stirring magnetic bar or due to centrifugal force. Platelets are hyper-reactive to chemical stimulation and the release of platelet granule contents (eg ATP) together with other membranous lipid metabolites, thromboxane A2 and malondialdehyde is markedly enhanced. The lipid soluble antioxidant, vitamin E is depleted from various blood compartments. The findings suggest that circulating platelets in splenectomized thalassemia are continuously attacked by yet to be identified blood borne factor(s) and the defective platelets could play a pivotal role in the pathogenesis of hypoxemia. PMID- 1298991 TI - Increase in spontaneous platelet aggregation in beta-thalassemia/hemoglobin E disease: a consequence of splenectomy. AB - Clinical symptoms related with disturbances of the circulatory system are often observed in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients after splenectomy. Pulmonary thrombosis is one of the important contributing factors. However, the pathogenesis of this phenomenon was not known. Previous studies on platelet functions were controversial as platelet-rich plasma (PRP) was employed for all of the studies. By centrifugation, most of the hyperactive platelets were excluded before platelet aggregation tests were performed. Besides, the role of red cells related to platelet aggregation was not investigated. In this study, a platelet function test was designed to avoid these two handicaps of previous work as mentioned, by using whole blood from 15 normal and 40 beta-thal/HbE patients (15 nonsplenectomized and 25 splenectomized) to study spontaneous platelet aggregation. The principle of the test was to evaluate platelet number in whole blood by electronic platelet counter at time 0 (45 minutes after blood collection) and this number was used as 100% of free unaggregated platelets. Then the same specimen of whole blood was incubated at 37 degrees C with continuous stirring by magnetic stirrer in an aggregometer for 8 minutes; at 1 minute intervals free unaggregated platelets were evaluated and calculated as a percentage of the initial control value. The results indicated increased spontaneous platelet aggregation in whole blood of post-splenectomized beta thal/HbE patients. The residual free platelet number were 24% at 8 minutes after incubation. Effects of red blood cells on spontaneous platelet aggregation were studied by mixing autologous beta-thal/HbE red cells obtained from splenectomized and non-splenectomized patients with platelet rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298992 TI - Spontaneous platelet aggregation in thalassemic children and adolescents. AB - Spontaneous platelet aggregation was studied in 51 children and adolescents, comprising 30 nonsplenectomized thalassemic patients, 12 splenectomized thalassemic patients and 9 normal children. Spontaneous platelet aggregation was significantly increased in whole blood and platelet-rich plasma of splenectomized thalassemic patients but not in nonsplenectomized cases. PMID- 1298993 TI - Development of a new method for detection of platelet factor 3 like activity. AB - We asked the question, "Can thalassemic erythrocytes play some role in alteration of the hemostatic system?", because clinical examination of thalassemic patients shows symptoms and signs related to alterations in hemostatic and circulatory systems, and thalassemic erythrocytes are different from normal erythrocytes. We obtained one of the answers to the question: The erythrocytes of postsplenectomized patients of beta-thalassemia/HbE disease could stimulate their own platelets to aggregate spontaneously. To know the role of erythrocytes in platelet aggregation, we wanted to examine the effect of thalassemic erythrocytes on the coagulation system by focusing of PF3-like activity of erythrocytes, because PF3-like activity of the ghosts of erythrocytes had been reported. For the study, we tried to develop a technique that was accurate and sensitive enough to detect PF3-like activity of blood. The system we developed was the following: 1) We activated the intrinsic coagulation pathway of commercial standard plasma by ellagic acid. 2) CaCl2, a fixed amount of PF 3 and synthetic thrombin inhibitor MD 805 were added to the reaction mixture. 3) At a fixed time, thrombin activity in the mixture was measured by using S-2238 as a substrate. At full activation of the contact system by ellagic acid, the amount of thrombin formed in a certain time depended on the amount of PF3-like substances such as cephalin, freeze-thawed platelets or ghosts of erythrocytes added to the test system, indicating that PF3-like activity of those substances can be measured by the activity of thrombin generated in a fixed time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298994 TI - Detection of PF3 availability in whole blood from volunteers and beta thalassemia/HbE patients: a promising method for prediction of thrombotic tendency. AB - The platelet factor 3 (PF 3) plays a very important role in activation of coagulation factors and is regarded to be available during activation of platelets. However, membrane fraction of erythrocytes is also shown to have PF 3 like activity, suggesting that the abnormal erythrocytes may accelerate the activation of platelet by forming thrombin on their abnormal membrane or by way of other factors of the abnormal erythrocytes, and may increase the availability of PF 3 in whole blood (WB). To examine this hypothesis, we developed a method for determination of PF 3 activity, because the method now available for the PF3 determination could not detect changes in PF 3 activity with time. The principles of our method were as follows: 1) The reaction system was adjusted so that the amount of thrombin generated in a fixed reaction time correlates with the amount of PF 3. 2) To avoid inhibition of thrombin activity by antithrombin III, a synthetic thrombin inhibitor, MD 805, was added to the system and the activity of thrombin generated was measured by synthetic thrombin substrate S-2238 using A405 as an indicator of the availability of PF3. The results obtained by the method were the following: WB taken from volunteers showed A405 of 0.12 +/- 0.02 at 30 minutes after blood collection and then the A405 increased to 0.27 +/- 0.03 at 90 minutes. However, one volunteer showed the value of 0.59 at 90 minutes, though the value at 30 minutes was 0.16. The platelet number in his WB did not change during the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298995 TI - Morphological assessment of platelet activation in thalassemia. AB - Platelets from patients with beta-thalassemia/hemoglobin E, both splenectomized and nonsplenectomized cases, were examined in comparison to those from normal subjects by scanning electron microscopy. In normal subjects, the majority of platelets were discoid (mean +/- SD, 81.0 +/- 3.9%) with 17.3 +/- 3.5% type I spherical shapes (platelet with long axis/short axis greater than 1.1) and 1.3 +/ 1.0% type II (long axis/short axis = 1.0-1.1). The thalassemic patients had significant lower percentage of discoid platelets (60.9 +/- 8.1% in nonsplenectomized patients, 49.2 +/- 9.1% in splenectomized patients) and increase in spherical platelets (nonsplenectomized patients had 36.6 +/- 8.3% type I, 4.0 +/- 1.5% type II; splenectomized patients had 43.4 +/- 7.9% type I, 8.3 +/- 4.5% type II). Study of platelet reversibility from pseudopods to smooth surface showed that thalassemic platelets had poorer reversibility than normal platelets. Splenectomized patients had lower platelet pseudopod reversibility than nonsplenectomized cases. The shape changes and impaired reversibility of platelet pseudopods may be associated with the high tendency of pulmonary thrombus in beta-thal/HbE patients. PMID- 1298996 TI - Protein C and protein S deficiency in thalassemic patients. AB - To investigate the status of the protein C-protein S anticoagulant pathway in thalassemic patients, we measured protein C and protein S levels of plasma of 30 adults and 18 children with beta-thalassemia/HbE disease, beta-thalassemia major and HbE disease. Mean +/- 1 SD values of protein C, protein S and other coagulant proteins produced by the liver were as follows: protein C 50.4 +/- 17.2%; protein S 58.8 +/- 25.5%; antithrombin III 78.1 +/- 12.8%; PLG 86.4 +/- 18.4%; prothrombin 71.0 +/- 13.1%; factor VII 72.7 +/- 21.5%; and factor X 79.2 +/- 15.6%. Protein C and protein S levels of thalassemic patients were significantly lower than those of other coagulant proteins produced by the liver. Decrease in protein C level was stronger than that of proteins S. gamma-Carboxylated protein C levels of splenectomized patients were significantly lower than those of nonsplenectomized patients. Severe decrease of protein C and protein S may be responsible for occurrence of thrombosis in thalassemic patients. PMID- 1298997 TI - The molecular basis of alpha-thalassemia in Thailand. AB - Alpha thalassemia is the most common single gene mutation worldwide. In Thailand there exists 15-30% alpha-thalassemia carriers distributed throughout the country. DNA analysis by Southern blot hybridization reveals that the two major alpha-thalassemia alleles, alpha-thalassemia 1 and alpha-thalassemia 2 have different extents of alpha-globin gene deletion. In alpha-thalassemia 1, approximately 20 kb of DNA including the two linked alpha 1-and alpha 2-genes are removed and only the alpha-globin gene is intact. Total deletion of the alpha globin gene cluster is rarely observed. In contrast, only one alpha-globin gene is deleted in alpha-thalassemia 2 of which two types have been detected, one involving a deletion of 4.2 kb of DNA (leftward type, -alpha 4.2) and another of 3.7 kb (rightward type, -alpha 3.7); the latter being more common than the former in Thailand. Compound heterozygosity for alpha-thalassemia 1 and alpha thalassemia 2 results in HbH disease while homozygosity for alpha-thalassemia 1 leads to Hb Bart's hydrops fetalis, the most severe form of thalassemic disease. Three alpha-thalassemic hemoglobinopathies have been detected in Thailand, two of which produce a remarkable reduction in gene product. Upon interacting with alpha thalassemia 1 gene they can lead to HbH disease. The most common in this group is Hb Constant Spring which arises from mutation of the termination codon in the alpha 2-gene resulting in an elongation of the alpha-globin chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1298998 TI - The thalassemic red cell membrane. AB - The underlying cause of pathology in thalassemia is the premature destruction of red cells, both in the bone marrow and by the reticuloendothelial system. It is generally accepted that the presence of unpaired excess globin chains is the primary circumstance leading to such membrane alterations as oxidation of phospholipids, modification of cytoskeletal proteins and their interactions, reduced membrane-associated ATPase activities, and enhanced permeability of cations. Such perturbations in turn result in the exposure of outer surface neoantigens, enhanced binding of autoantibodies and complement fixation to the outer red cell surface. These factors contribute to the observed distinctive morphologies, increased rigidity and decreased deformability of the thalassemic red cells. In alpha-thalassemic red cells, excess beta-globin chains form homotetramers, Hb H, which are relatively stable and will only damage red cell membrane when precipitated as inclusion bodies, whereas excess alpha-globin chains cannot form such homotetramers and upon synthesis rapidly bind to the cytoplasmic side of the beta-thalassemic red cell membrane, even in young erythroblasts. This difference in properties of the excess globin chains may offer an explanation for the variation in clinical severity observed between these two forms of thalassemia. PMID- 1298999 TI - Size distribution curves of blood cells in thalassemias and hemoglobin H diseases. AB - Thalassemias and hemoglobinopathies in Thailand have been examined with a blood cell counter based on electroimpedance principle and obtained size distribution curves of red cells and platelets. Among various disorders, beta thalassemia/hemoglobin E and homozygous hemoglobin Constant Spring showed severe anemia. Their red cell size distribution curve shifted to the left and overlapped with the platelet size distribution curve. Red cell distribution width expressed by coefficient of variation and the degree of the overlapping were stronger in beta-thalassemia/HbE than HbH. Heterozygous beta-thalassemia showed a narrow red cell distribution curve width with small standard deviation and low England's value. Although the overlapping of size distribution curves cause inaccurate red cell count and platelet count, careful observation of the size distribution curves was proved to have high diagnostic value. PMID- 1299000 TI - Biophysical changes of red cells with thalassemia-like abnormal hemoglobin. AB - Hemoglobin (Hb) E and Hb Constant Spring (CS) are known to have thalassemia-like effects. Investigation on the red cell physical changes in these two abnormalities has been done to clarify the diversity of red cell changes between thalassemia and thalassemia-like abnormal hemoglobin (Hb E represents beta thalassemia and Hb CS represents alpha-thalassemia). Eleven cases with homozygous Hb CS (CS/CS), 7 homozygous Hb E subjects (E/E) and one double heterozygous case with Hb CS and Hb E were included in this study. The red cells were analyzed by the H* 1 hematology analyzer. The E/E red cells had significantly smaller MCV than the CS/CS red cells (p < 0.001). The smaller MCV of E/E red cells was attributed to markedly increased percent microcyte (p < 0.001) and significantly lower percent macrocyte (p < 0.001) as compared to CS/CS red cells. Degree of heterogeneity in cell volume as indicated by red cell distribution width (RDW) was not significantly different between the two abnormal hemoglobin containing red cells. It was also noted that the CS/CS cases had a more significant increase in small RBC than the E/E cases (p < 0.001). Significant lower intraerythrocyte hemoglobin concentration values of the CS/CS red cells as compared to E/E red cells were shown: cellular hemoglobin concentration mean (CHCM) (p < 0.001), percent hyperchromic red cell (p < 0.001) and hemoglobin distribution width (HDW) (p = 0.0367). Higher values for the CS/CS red cells were MCH (p < 0.001) and percent hypochromic red cells (p < 0.001). Red cells from both genotypes had significant decreases in red cell deformability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299001 TI - [Secondary neoplasms of the kidney. Tomodensitometric diagnosis]. PMID- 1299002 TI - [Urinary tract infections at the hospital and the ambulatory service: etiology and laboratory diagnosis]. AB - An aetiology study was conducted into urinary tract infections (UTI) in order to compare hospital infections with those in outpatients identified from samples sent to the laboratory by general practitioners. Urine culture analysis was performed on 3,483 samples of which 740 came from hospital patients and 2,743 from outpatients. The diagnosis of UTI was based on new criteria: not only the assessment of bacterial proliferation but also clinical factors like sex, symptoms, sampling technique and urinary leucocyte count and the traditional threshold of 10 units forming colonies (UFC/ml) was ignored. In other words the following were all considered positive: all bacterial growths > or = 10(5) UFC/ml independent of other data, all those > or = 10(2) UFC/ml in symptomatic women, those > or = 10(3) UFC/ml in symptomatic men and those > or = 10(2) UFC/ml in catheterised patients. In cases supplied with incomplete anamnestic data bacterial proliferations in the 10(2)-10(5) UFC/ml range were considered positive if the leucocyte count was also significant. The frequency of the various micro organisms isolated from the positive urine cultures of the two group was then assessed. The study revealed that among outpatients relatively innocuous bacterial like E. Coli, Klebsiella and Proteus accounted for over 75% of UTI cases, but less than 44% among hospital patients. By contrast, more "serious" bacteria like Pseudomonas, Acinetobacter and Serratia were identified in about 20% of hospital cases but only about 5% of outpatients. Finally a comparison was made between in- and outpatient multibacterial UTI which were found to be more common and more aetiologically heterogeneous in hospital patients than in outpatients. PMID- 1299003 TI - [Treatment of urinary infections with ticarcillin and clavulanic acid (Clavucar) by the intramuscular route]. AB - 20 patients suffering from hospital-acquired UTI received intramuscularly ticarcillin 1 g and clavulanic acid 200 mg for 8 days. At the end of antimicrobial therapy 84.2% of the pts presented sterile urine. After 2 weeks 68.4% of the pts continued to have sterile urine. No significant side effects were registered. The results demonstrate that the association of ticarcillin with clavulanic acid can be considered a useful option in hospital acquired UTI. PMID- 1299004 TI - [Primary lymphoma of the kidney. Description of a case and brief review of the literature]. AB - Stage IV disseminated non-Hodgkin lymphomas show kidney involvement with frequency; on the contrary, primary kidney lymphoma, as the sole presenting feature, is a very rare disease. Non-Hodgkin histological pattern, atypical symptoms, marked discrepancy between parenchymal involvement and impairment of renal function are the main features of this tumor. A case-report of a primary kidney non-Hodgkin lymphoma will be described; a short review of literature on this subject will be discussed. PMID- 1299005 TI - [Oncocytoma in a horseshoe kidney]. AB - Oncocytoma is a neoplasm that constitutes 4-5% of tumors located in the renal parenchyma. It was studied for the first time by Zippel in 1942 and since than nearly 150 cases have been described. The association between neoplasm and horseshoe kidney is extremely rare. The horseshoe kidney is a malformation which often becomes complicated by infection, hydronephrosis and calculosis, but very rarely by a neoplasm (only 113 cases). The Authors report a case of oncocytoma in the horseshoe kidney and discuss the diagnostic, clinical and therapeutical aspects. PMID- 1299006 TI - [Macroscopic hematuria secondary to segmental enteritis, Description of a case with special attention to the histopathological changes in the bladder]. PMID- 1299007 TI - [Comparison between biopsy data and the resistive index obtained by Doppler echography in the evaluation of the transplanted kidney]. AB - Doppler sonography is nowadays considered as a "first step" tool for diagnosis of vascular complications in kidney transplantation. Quite recently, it has been sometimes considered useful and effective investigation in order to obtain information about parenchymal dysfunctional pathologies, particularly about acute rejection. This has been obtained by studying the variation of resistive indexes. The goal of the following investigation was compare Doppler sonography data and histological examination in 50 kidney transplanted recipients in whom the renal biopsy was performed on a clinical basis. In the Authors' experience. Doppler sonography and study of the resistive index does not offer any reliable help in differentiating acute rejection from cyclosporine A toxicity. PMID- 1299009 TI - [Vascular access for hemodialysis. Clinical experience]. AB - Seventy-nine arteriovenous fistulas for periodic hemodialysis were created in 62 uremic patients: 64 primary vascular accesses and 15 salvage operations for malfunctioning fistulas. Sixty-three distal and 1 proximal arteriovenous fistulas between the radial artery and the cephalic vein, were created as primary vascular access. The utilization time of the primary arteriovenous fistulas was longer than 5 years in 34%, 3-4 years in 25% and 0-2 years in 41% of cases. Eleven fistulas evidenced thrombosis: a salvage operation (resection-anastomosis) was possible for 9 (89%). A salvage operation was possible for 100% of poor flow fistulas. The utilization's time of the salvage fistulas is longer than 5 years in 15%, 3-4 years in 15% and 0-2 years in 70% of cases. PMID- 1299008 TI - [Determination of bone mineral content and correlations with calciotropic hormones in periodic hemodialysis patients]. AB - The investigation on several forms of uremic osteodystrophy by means of bone mineral content (BMC) measurement led to contradictory conclusions. BMC in 27 patients on periodical hemodialysis treatment was measured correlating it to the seric levels of Ca, P, Mg, alkaline phosphatase (AP), calcitonin (Ct), osteocalcin (BGP), intact parathormone (PTHi), c-terminal and mean molecule PTH. Patients on dialysis treatment from a long period of time showed high AP and low BMC levels. This correlation proved significant just for the values recorded at a third distal site of radius. Patients with BMC under the normal range showed higher BGP levels and a longer period of dialytic treatment than those presenting normal BMC. The former showed a Ct inverse correlation as to age and mineralization indexes. Higher values of Ct and BMC have been reported in males rather than in females. Hence BMC is not suited to investigate different kinds of uremic osteodystrophy. Seric PTH dosage is certainly best fitted to discriminate patients affected with hyperparathyroidism from those with low turnover osteodystrophy. BMC determination is a valid support to evaluate the bone mineral loss in patients on haemodialysis treatment. It significatively correlates to the duration of the dialytic treatment; it is higher in female than in male population; it mainly affects cortical components rather than trabecular ones and is related to a seric Ct decrease. PMID- 1299010 TI - [Nursing story. The forgotten Thursday medicine]. PMID- 1299011 TI - [Patient Complaint Tribunal. Many complain about anesthesia]. PMID- 1299012 TI - [Continuing education--cross-professional offer not sufficient]. PMID- 1299013 TI - [Latvia: a study of needs]. PMID- 1299014 TI - [Ethics. The search for genes]. PMID- 1299015 TI - [Psychiatric. Portrait of a restructure]. PMID- 1299016 TI - [Ireland. 3 kinds of patients]. PMID- 1299017 TI - [Ireland. On the way towards a new kind of nursing]. PMID- 1299019 TI - [Ireland. Sisters of Mercy]. PMID- 1299018 TI - [Ireland. Everyday, children and income]. PMID- 1299020 TI - [Asylum seekers--12 refugees in the same cabin]. PMID- 1299021 TI - [Nurses' co-responsibility]. PMID- 1299022 TI - [Research--a glass of water for the patient]. PMID- 1299023 TI - [Nursing story. A true Copenhagen outing]. PMID- 1299024 TI - [Exchange--from Lithuania to Aarhus]. PMID- 1299025 TI - [Hospitals--new charge by physicians on equally worthy leadership]. PMID- 1299026 TI - [Ireland. In the footsteps of Catherine and Fiona]. PMID- 1299027 TI - [EEC: Danish model for a better life for the mentally ill]. PMID- 1299028 TI - Dentists and the employment law woes. PMID- 1299029 TI - The changing face of dentistry. PMID- 1299030 TI - Personality, self-esteem, stress, and satisfaction among Texas dentists. AB - Do the personality styles of dentists significantly influence their sense of well being in their profession? A recent study using the Bi/Polar Inventory of Core Strengths differentiated 218 Texas dentists into eight personality profiles. Patterns VII and V (both risking and practical) as a group reported significantly higher self-esteem, higher ability to cope with stress, lower psychological distress, higher satisfaction with dentistry, and greater likelihood of choosing dentistry again as a career, than did Patterns III and IV (both thinking and theoretical). The results suggest that Patterns VII and V may be the most compatible with dentistry, and Patterns III and IV the least compatible. Also, the practical orientation (preferred by nearly 80% of the Texas dentists sample over the theoretical orientation) may be the single most influential personality trait in terms of compatibility with dentistry. Implications arise in career counseling, dental school admissions committees, and counseling dentists dissatisfied with. PMID- 1299031 TI - [The expression of 130kDa mosquitocidal protein gene of Bacillus thuringiensis subsp. israelensis in Bacillus subtilis]. AB - Two recombinant plasmid pFZ1 and pFZ2 containing Bti 130kDa mosquitocidal protein gene in opposite insertion orientation were constructed. The expression of 130kDa mosquitocidal protein of Bti in Bacillus subtilis was confirmed by western blotting. The mosquito-larvicidal activity against the larvae of Aedes albopictus was shown by the bioassay. PMID- 1299032 TI - [Purification and characterization of hec toxin produced by Aeromonas hydrophila]. AB - An extracellular toxin produced by Aeromonas hydrophila from cultured crucian carp with septicemia was detected. The toxin was purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and Sephadex G-100 gel filtration. The factor was a single polypeptide with a molecular weight of 52.5kd determined by SDS-PAGE. The heat-stable toxin possesses hemolytic, enterotoxic and cytolytic activities. The hemolytic activity on human erythrocytes was 3.81 x 10(3) HU/mg, CD50 for Vero cell was 0.26 microgram. The LD50 for crucian carp and mice was 4.44 micrograms and 3.58 micrograms respectively. The toxin was neutralized py homologous antibodies. The toxin shows unique characteristics as compared with other known bacterial toxins therefore the authors propose to name the toxin "hec" toxin. PMID- 1299034 TI - [The effect of plasmids on the resistance of E. coli to phages]. AB - The introduction of the ColV, I-K94 or R124 plasmid into Escherichia coli K12 resulted in resistance to certain phages. Derivatives of E. coli carrying the plasmid R124 and ColV, I-K94 were resistance to the phages T4, Mel comparing with the plasmid-free parent and the plasmid ColV, I-K94 conferred resistance to the phage Tull*. It suggested that an envelope change caused by the plasmids might be responsible for the resistance because most of the phages fell to absorb to the plasmid-bearing E. coli cells. PMID- 1299033 TI - [A survey of T-2 toxin in wheat by an indirect enzyme-linked immunosorbent assay]. AB - The survey of T-2 toxin in wheat randomly sampled in nine provinces was carried out, employing an indirect competitive enzyme-linked immunosorbent assay. Among 330 samples, 264 samples (80%) showed positive results. The mean concentrations was 53.3 ppb. and maximal concentration was 1122.0 ppb. It was also detected high concentration (84.5-1064.4) of T-2 toxin in human intoxication wheat samples in 1991. The investigation also showed that there existed close relationship between the level of T-2 toxin contamination and the epidemic of wheat scabby. PMID- 1299035 TI - [Use of the preparation Iso Mack Retard 60 mg I 120 mg in the treatment of patients with advanced ischemic heart disease]. AB - The purpose of the study was an evaluation of the effectiveness of the preparation ISO MACK RETARD in capsules of 60 mg and 120 mg in patients with advanced exacerbated ischaemic heart disease. The study included 72 patients, in 61 (84.7%) of them very good result treatment, estimated subjectively, was achieved. ISO MACK RETARD in capsules of 60 and 120 mg was well tolerated; in the studied group no side effects were observed. PMID- 1299036 TI - [Surgical treatment of secondary complications of myocardial infarction]. AB - The results are presented od surgical treatment of 18 patients operated on in the Cardiosurgery Department, Institute of Cardiology, Medical Academy in Lodz, in the years 1985-1989, for complications of myocardial infarction. The material includes such complications as: post-infarction perforation of the septum, and post-infarction aneurysm of the left ventricle. The usefulness of specialized examinations is shown in qualifying the patients for operation, and the method is presented of carrying out operations in these patients in extracorporeal circulation. Good results of surgical treatment were achieved. PMID- 1299037 TI - [Effect of treatment with HDM vaccine on selected immune parameters in children with bronchial asthma]. AB - The purpose of the study was to trace the changes of certain parameters of humoral and cell-mediated immunity in children with asthma who received the HDM Bencard vaccine as specific immunotherapy. Among the immune parameters the levels of IgG, IgA and IgM and the phagocytosis index were determined, the E-rosette test and the HBT reduction test were done before the beginning of the treatment, after 3 months, 9 months and 3 years of desensitization. The results were subjected to statistical analysis, presented in tables and in diagrams. Of the three determined immunoglobulins only the IgG increased significantly, while the titres of IgA and IgM remained unchanged. Before desensitization the values of the per cent of T-cells in the E-rosette test were below the accepted normal level. During HDM desensitization the per cent of T-cells rose. The phagocytosis index and the NBT reduction test were lower in the asthmatic children than in healthy ones but during the treatment with HDM they reached significantly high values. These results confirmed that mechanism of the action of this immunotherapy is a complex one and influences several structures of the immune system. Raised values of the studied parameters during desensitization correlated with an evident improvement of the clinical status and marked reduction of the frequency of asthma attacks. During the treatment with the HFM vaccine no side effects of this therapy were noted. PMID- 1299038 TI - [Recurrent abdominal pain in children]. AB - In the paper the results are presented of an analysis of the causes of recurrent abdominal pain in 294 children hospitalized at the Gastroenterology Department, Childrens Health Centre, and the accepted diagnostic programme is evaluated. The children were referred to the CHC, as a rule with a suggestion of organic causes of recurrent abdominal pain. On the basis of carried out examinations the following was diagnosed: in 111 children organic causes (37.8% of the studied group), in 94 children recurrent abdominal pain of functional aetiology (32%), in 53 children psychological background (18%), and in 36 children mixed organic and functional background. These proportions between those groups is the result of the selection carried out at earlier stages of the diagnostic process. In the paper, the correctness and validity of the accepted diagnostic programme are also demonstrated. PMID- 1299039 TI - [Clinical-morphologic analysis of children dying of intoxication with Amanita phalloides]. AB - The results were subjected to analysis of 23 autopsies carried out in children dying of intoxication with Amanita phalloides. The correlation of the pathomorphological findings with the clinical picture and biochemical pattern was evaluated. The morphological changes were also presented in organs other than the liver which is recognized as the target organ for Amanita phalloides toxins. PMID- 1299041 TI - [Results of treatment with ofloxacin for inflammatory conditions in male reproductive organs]. AB - The results are presented of the clinical and microbiological studies of the patients of the Andrological Outpatient Clinic in Warsaw, who were examined for explaining the causes of marital infertility or for elucidation of the cause of testicular pain. Thirty-two men aged 21 to 42 years were chosen, in whom semen investigation demonstrated presence of leucocytes in numbers exceeding 10 per field of vision and with clinical signs of inflammatory process in the male reproductive organs (10 patients) and without clinical signs (22 patients). The patients in whom semen cultures demonstrated presence of bacteria sensitive to ofloxacin were treated with the preparation Tarivid Hoechst for 10-20 days in daily doses of 2 x 200 mg. The clinical signs of inflammation of the reproductive organs regressed in 100% of cases, and in 64% of cases no leukospermia was found after the treatment. PMID- 1299040 TI - [Usefulness of hysteroscopy in the diagnosis and treatment of intrauterine adhesions]. AB - During hysteroscopy intrauterine adhesions were found in 96 patients in a group of women with disturbances of fertility and menstruation. The diagnosis and treatment were carried out with a Wolf hysteroscope using CO2 as the expanding gas. The purpose of the study was evaluation of the effectiveness of treatment of these adhesions by means of hysteroscopy. Normal menstrual bleeding after this treatment was achieved in 75% of the treated patients, and 51% of the patients conceived. Hysteroscopy was useful in the diagnosis, treatment and posttreatment control in cases of Asherman adhesions. PMID- 1299042 TI - [Minipress in the treatment of prostatic adenoma]. AB - Own results are presented of the use of Minipress in the conservative treatment of prostatic adenoma. On the basis of literature survey, the indications are discussed to this treatment. PMID- 1299043 TI - [Treatment without plaster cast of intra-articular fractures of calcaneus united by means of a kirschner wire bundle]. AB - A treatment without plaster cast is presented of intra-articular fractures of calcaneus. In nine patients after fracture reduction by the Westhues method or by operation, the fragments were united by means of divergent bundle of Kirschner wires, introduced from the side of calcaneal tuber. The obtained stabilization made possible an early rehabilitation treatment. In no case a secondary displacement of fragments occurred after removal of uniting wires. Poor result was noted only after surgical treatment complicated with osteitis. PMID- 1299044 TI - [Knee joint cyst]. AB - Ninety cases of knee joint cysts were treated surgically. This included 50 patients with rheumatoid arthritis, 22 patients with degenerative-deforming changes, ten children with true cysts, and eight ones with post-traumatic cysts. Double-contrast X-ray examination with Lipiodol Ultra-fluid and air is of the best diagnostic value. All cases of knee joint cysts were treated surgically with a careful plastic closure of cyst gate. For this purpose the authors used the arcus tendon of the semi-membranous muscle. In cases of rheumatoid arthritis and degenerative changes cyst removal was preceded by synovectomy of the knee joint. Early and remote were good, no recurrence was observed. PMID- 1299045 TI - [A case of malignant pericardial mesothelioma]. AB - A case is described of malignant pericardial mesothelioma of epithelial type. The diagnosis was made on the basis of autopsy. The patient, a 46-year-old construction technician fell ill with symptoms of pericarditis. Initially, it was connected with a flu infection, and later with tuberculosis. During the 11-week long treatment, a rapidly progressing worsening of health condition was observed. Death was caused by pericardial mesothelioma complicated with embolism of the pulmonary arteries. PMID- 1299046 TI - [Myxoma of the left atrium suggesting a connective tissue disease]. AB - A case is presented of myxoma of the left atrium suggesting a connective tissue disease. In the foreground were musculo-articular symptoms, sub-febrile states, considerable loss a body weight. At the same time an increased sedimentation rate, hypergammaglobulinaemia, increased level of IgG and IgM, high CRP level, and the presence of antinuclear antibodies and LE cells were noted. The diagnosis of myxoma was made on the basis of echocardiographic examination. After surgical resection of the tumor all symptoms regressed, and a normalization was observed of the formerly observed abnormalities in the laboratory investigations. PMID- 1299047 TI - [Hemolytic microangiopathic anemia occurring in a patient with simultaneous cancer in two organs]. AB - A case is described of rarely observed hemolytic microangiopathic anaemia associated with gastric and renal cancer. It is stressed that the diagnosis of this anaemia should be for the doctor an indication for searching for the cause of primary disease in which damage to the small blood vessels develops. PMID- 1299048 TI - [Primary aorto-intestinal fistula as a diagnostically difficult complication of ruptured abdominal aortic aneurysm]. AB - Three cases are presented of a rare complication of abdominal aorta aneurysm, that is its rupture into the gastrointestinal tract. In two cases the aneurysm ruptured into the duodenum, and in one case into small intestine. The authors call attention to the variety of symptomatology and diagnostic difficulties with the primary aorto-intestinal fistula. This is true especially of cases in which the rupture is the first and not infrequently the only symptom of the aneurysm. The rupture of the abdominal aorta aneurysm into the gastrointestinal tract is still fraught with a very high mortality; out of three patients with primary aorto-intestinal fistula only one was saved. PMID- 1299050 TI - [A case of histiocytosis of Langerhans cells]. AB - A lethal case is presented of disseminated for of histiocytosis of Langerhans cells in 16-month-old girl. In the clinical course predominated high fever, opportunistic infections, cell-mediated and humoral immunity disturbances, and gross hepatocellular damage which made impossible carrying out of the treatment with cytostatics. The advances in immunological investigations in these patients are more widely discussed as well as the use of thymus hormones. PMID- 1299049 TI - [Pericardial mesothelioma as a very rare cause of recurrent cerebral emboli]. AB - We described a rare case of a patient with pericardial mesothelioma, which caused recurrent embolism in systemic and cerebral circulatory systems, leading to the death. Symptoms concerning central nervous system dominated clinical investigation results. PMID- 1299051 TI - [Ellis van Creveld syndrome (chondroectodermal dysplasia) in a 7 year old girl]. PMID- 1299052 TI - [Problems diagnosing cat scratch disease]. AB - The diagnosis of cat scratch disease is hampered by the fact the basic laboratory investigations fail to demonstrate characteristic changes of this disease, and the diagnosis is based usually on epidemiological history and the clinical symptom complex. The diagnosis is confirmed by the complement binging test with the antigen obtained from pathologically changed lymph nodes with values over 1.5 being pathognomonic for the disease, and by the cutaneous tests of Hanger-Rose and Mollaret. The authors present 2 cases treated for the disease stressing differences in its course. PMID- 1299053 TI - [Passive smoking as the cause of life-threatening intoxication in a child]. AB - A case of poisoning with tobacco smoke was observed in a child aged two years exposed to this smoke. The child had COHb concentration 18%, pallor, tachycardia, tachypnoea, raised blood pressure, tonic seizures and loss of consciousness. PMID- 1299054 TI - [Modern views about the role of lymphatic tissue in Waldeyer's ring as immunologic processes]. PMID- 1299055 TI - [Studies of the lymphatic system in mice infected with Trichinella pseudospiralis as well as infected and stimulated by Phytohaemagglutin (PHA-P)]. AB - Mice CFW were infected per os with Trichinella pseudospiralis (150 larvae/mice). The mice were divided in two groups: nonstimulated and stimulated intraperitoneally with PHA-P at dose 10 mg/kg body weight. The animals were killed 7, 14, 21, 28, 42, 56, 70 and 150 day post infection (d.p.i.). Spleen et mesenteric lymph nodes were examined histopathologically (Hematoxylin-Eosin) and histochemically (nonspecific esterase reaction) for differentiation of T lymphocytes. The obtained results reveal that T. pseudospiralis infection caused weak mobilisation of mouse lymphatic system lasting only to 70 day of experiment. In the lymphatic organs of infected mice small number of T lymphocytes were observed mostly between 28 and 56 d.p.i. The intraperitoneally stimulation with PHA-P give rise to caused only little mobilisation of lymphatic tissue and small increase of T lymphocytes number. The obtained results were compared with analogic earlier experiments with T. spiralis infection. PMID- 1299056 TI - [Influence of cadmium on the course of intestinal and muscular phases in mice infected with Trichinella spiralis]. AB - At the first experiment 20 Swiss male mice were infected with 100 larvae and 20 mice with 500 larvae T. spiralis per mouse. Two days after infection (d.a.i.) mice orally received 1.5 mg Cd (water solution CdCl2) each. 40 mice were infected only T. spiralis as control. At the second experiment muscle larvae used were isolated from mice (from the first experiment) which received Cd. 20 mice were infected with 100 larvae and 20-with 500 larvae per mouse. Two d.a.i. mice received 1.5 mg Cd. Mice from both experiments were killed at 5, 10, 20 and 42 d.a.i. Total number of adult T. spiralis worms present in the small intestine and muscle larvae were recovered by conventional technique. Results of the first experiment: the number of adult worms and muscle larvae recovered from mice received Cd. were statistically significant lower as in control. Results of the second experiment: the mean number of adult worms in experimental group and in control were the same but the mean number of larvae per gram of mice muscle were significant higher as in control. PMID- 1299057 TI - Activity of natural killer (NK) cells in the course of experimental trichinellosis in mice. AB - B6C3F1 mice were infected with 200 or 500 larvae of Trichinella spiralis per mouse and pulmonary NK cell-mediated clearance of semisyngeneic tumour cells was determined in vivo on days 10, 20, 30, and 60 after the infection. Cytotoxic activity of NK cells in the lungs was substantially elevated on days 20 and 30 after challenge with both "doses" of the parasite. At the same time large granular lymphocytes (LGLs) as well as cells expressing surface asialo-GM1 molecules were isolated in elevated numbers from spleens of the infected as opposed to the normal mice. Expression of other markers of differentiation, such as THy 1, CD4, and CD8 was also enhanced on splenocytes isolated from the infected mice on day 30 but not 20 after administration of the larvae. The present results indicate that NK cell-mediated activity in vivo is stimulated above the baseline level during migration and early muscle phases of the infection with T. spiralis in mice. The possible impact of this effect upon the course of trichinellosis as well as upon the growth of tumours in the infected host is discussed. PMID- 1299058 TI - Activity of specific IgG, IgM and IgE antibodies in human trichinellosis. AB - The activity of IgG, IgM and IgE antibodies to somatic antigen of Trichinella spiralis in the sera of patients with trichinellosis at various intervals after infection was examined by means of ELISA. Mathematical analysis of the dose response curves was used. Elevated level of IgG and IgM antibodies of relatively high avidity and of rather low IgE avidity was documented. Amount or avidity of IgG antibodies was found to be most useful for the diagnosis of trichinellosis (85% positive results in patients' sera). The isotype of IgM avidity constitutes a better diagnostic value than the amount of it (60% and 35% of positive results, respectively). PMID- 1299059 TI - [Influence of nalcrom (sodium cromoglycate) on the course of the intestinal phase of trichinellosis in mice]. AB - The influence of Nalcrom (sodium cromoglycate) on the course of the intestinal phase of trichinellosis in mice was investigated. The animals infected with 200 Trichinella spiralis larvae were treated with Nalcrom between 7-20 or 3-20 days after infection (d.a.i.). The drug was administered in two doses: 0.6 or 1.7 mg/mouse/day. In the all groups of animals received Nalcrom higher number of mast cells and eosinophils than in the control groups was observed. These results are the opposite of those obtained with Nalcrom in ulcerative colitis in man. PMID- 1299061 TI - Trichinellosis in the USSR (1983-1987), tendency to spreading. PMID- 1299060 TI - Efficacy of albendazole against Trichinella pseudospiralis and Trichinella spiralis in mice. AB - Albendazole (Smith Kline, Beecham) in a dose of 20 mg/kg/day was given to B6C3F1 mice exposed to 300 larvae of T. pseudospiralis or T. spiralis. The drug was introduced on days 2, 3 and 4; or 4, 5 and 6; or 18, 19 and 20 after infection. It limited the intensity of intestinal and muscle phases of trichinellosis. Given at the stage of maturation of adult forms and production of new-born larvae, the drug caused almost total elimination of both species from the intestines of mice and a decrease in the numbers of muscle larvae, with a tendency towards a greater reduction of larvae and adults of T. pseudospiralis. The drug did not change the course of infection when given at the phase of infectivity of larvae. PMID- 1299062 TI - Trichinellosis in Lithuania (1978-1987). PMID- 1299063 TI - Trichinellosis in France (1988-1990) PMID- 1299064 TI - Human trichinellosis in Italy. PMID- 1299065 TI - Trichinellosis in Poland (1988-1991) PMID- 1299066 TI - [Scientific cooperation of ITC with medical centers in Lithuania]. PMID- 1299067 TI - Trichinella species and intraspecific varieties. PMID- 1299068 TI - Ecological border of distribution of Trichinella nativa Britov et Boev, 1972 and T. nelsoni Britov et Boev, 1972. AB - According to the received data Trichinella nelsoni and T. nativa occupied different areas. T. nelsoni was localized in Africa and Mediterranean subregion of Palearctics, T. nativa occupied the continental territory of Eurasia and Neoarctics. Their distribution was limited by the threshold action of certain gradation of low temperatures. The joints of the species borders passed along the isotherm line of -5 - -6 degrees of January, where they made sympatric populations. Outside of this border these species were registered as allopatric populations. PMID- 1299069 TI - [The role of the nucleus in the mechanism of transformation of muscle after infection by Trichinella spiralis larvae. III. Morphometric analysis of the functional transformation of the muscle cell nucleus after infection]. AB - Morphometric investigations (using the convergence analysis method) of geometric parameters of nuclei and nucleoli of transformed muscle cells were carried in mice 15 days, 30 days and 6 month after infection with T. spiralis larvae. The analysis showed the largest increase of investigated the parameters of 15th day after the infection. The results of morphometric analysis are in agreement with the morphologic, ultrastructural and histochemical observations (published in I and II part) as for as functional changes of muscle cells in various stages of trichinellosis are concerned. PMID- 1299070 TI - Incidence of insulin-dependent diabetes mellitus in Warsaw, Poland, in children and young adults, 1983-1988. AB - The 5-year results of the incidence study of insulin-dependent diabetes mellitus (IDDM) in children (0-14 years) and young adults (15-29 years) which began in Warsaw on 1 July 1983 are presented. The overall number of new IDDM patients aged 0-29 registered in Warsaw during 5 years was 165. The average incidence rates in the age groups 0-14 and 15-29 were respectively 5.2 and 6.5 per 100,000 population in males and 4.5 and 4.4 in females. The highest incidence was observed in the age groups 25-29, 10-14 and 15-19 in males, and 5-9 and 25-29 in females. More patients reported the onset of their first symptoms in autumn and winter than in spring and summer. The IDDM incidence rates in Warsaw appear to be lower than those in some other countries for which data on IDDM at ages 0-29 years are available. PMID- 1299071 TI - Diabetes and impaired glucose tolerance in women aged 20-39 years. World Health Organization Ad Hoc Diabetes Reporting Group. AB - Age-standardized estimates of prevalence of diabetes mellitus and impaired glucose tolerance (IGT) are presented for women aged 20-39 years in 29 populations. In most cases, diabetes was uncommon (< 1%). Prevalence of diabetes was 1-3% in women in Italy and the United States, 7% in Fiji Indian and Aboriginal Australian women, > 10% in Nauruans and > 20% in Pima Indians. IGT was common (> 3%) in many communities. Prevalence of IGT exceeded 10% in black and Hispanic women in the United States, urban Indian women in the United Republic of Tanzania, Pima Indians and some Pacific populations. In one-third of the populations, prevalence of total glucose intolerance (diabetes and IGT combined) exceeded 10% in women in this age range. In many communities, over 50% of diabetes was undiagnosed prior to the survey. It is concluded that a substantial proportion of abnormal glucose tolerance during pregnancy will go undetected in the absence of screening programmes. An international study is required to define the risk to the mother and the fetus of various levels of glucose intolerance, with a view to formulating international guidelines for clinical practice. PMID- 1299073 TI - Diabetes mellitus in Egypt. AB - A series of surveys of diabetes mellitus (DM) have been performed in Egypt recently, using a common protocol and WHO criteria for diagnosis and classification. Average prevalence for the country as a whole for people above the age of 10 was 4.3%, with distinct geographical differences: 5.7% in urban areas, 4.1% in rural agricultural areas, and 1.5% in rural desert areas. In some secluded villages, DM was almost completely absent. Surveys among younger ages indicate prevalence of 0.01%, 0.06% and 0.14% among children at preparatory, primary and secondary school respectively. A high risk of DM is associated with family history of the disease, obesity, premature atherosclerosis and hypertension. The cost of ambulatory outpatient care for DM in Egypt is one of the lowest for Mediterranean countries. However, the cost of treatment of the various complications of diabetes is higher. The total direct cost of diabetes in Egypt in 1990 has been estimated at US$ 74.3 million, with indirect costs due to absenteeism from work adding a further US$ 11.8 million. PMID- 1299074 TI - Diabetes in Mexico--a serious and growing problem. AB - According to a recent national health survey, the prevalence of self-reported diabetes in Mexico is 1.2%, but this figure reflects the relative youth of the Mexican population. Age-specific estimates are similar to those for the United States of America, where crude prevalence is higher. Given that self-reporting usually underestimates prevalence by at least 50%, there may be as many as 1.7 million persons with diabetes in Mexico, with a prevalence of approximately 6% in the age range 30-64 years. The average age at death for Mexicans with diabetes is 57 years, compared to 69 years for the population as a whole. Diabetes is the fifth most important cause of death in the Mexican population, and the third cause in people over 45 years of age, in whom it accounts for 10% of all deaths. There is evidence for important increases in diabetes-related mortality over time. Most studies indicate high rates of complications in Mexicans with diabetes and data show that their average length of hospital stay is almost twice as long as for non-diabetic patients. The annual cost of diabetes to Mexican society may be estimated at US$ 15 million for metabolic control, US$ 85 million for additional health services and US$ 330 million for indirect costs--in total, approximately three-quarters of all government spending on health care, or approximately US$ 450 per known diabetic person per year. PMID- 1299072 TI - Diabetes in time of armed conflict: the Croatian experience. AB - During the summer of 1991, armed conflict broke out in the Republic of Croatia. This resulted in many deaths and the displacement of many persons, with population loss in some communities and additional population burden in others. Registration of diabetic persons has been compulsory in Croatia since 1975 and from available statistics compiled by the Vuk Vrhovac Institute for Diabetes in Zagreb it was known that in 1991 there were 111,096 diabetic persons in Croatia, 16% requiring insulin, 46% treated with oral agents and 38% using dietary treatment only. This information helped to plan adequate supplies during the emergency. Contacts with international organizations and friends were of value in overcoming shortages, the most useful gifts being battery-operated blood glucose measuring devices. A study in Zagreb failed to demonstrate an association between the stress of displacement and metabolic control. Somewhat unexpectedly, diabetes and its complications did not present a major public health problem during the first 8 months of the armed conflict, but the long-term effects of these events remain to be seen. PMID- 1299075 TI - Recent developments in the epidemiology of diabetes in the Americas. AB - The prevalence of diabetes recorded in population surveys in the American region varies from < 1% (rural Mapuche Indians aged 20 years and over, Chile) to almost 50% (Pima Indians aged 20 years and over, United States of America). The prevalence of non-insulin-dependent diabetes mellitus (NIDDM) was approximately 2.5 times higher among Mexican Americans than in non-Hispanic white Americans. In the Mexican Americans, prevalence followed a sociocultural gradient: 16% in low income barrios, about 10% in middle-income neighbourhoods and 5% in high-income suburbs in San Antonio, Texas. Data from the Hispanic Health and Nutrition Examination Survey indicate prevalence of diabetes in the age range 45-74 years of 24% for Mexican Americans, 26% for Puerto Ricans and 16% for Cuban Americans, compared to 12% for non-Hispanic whites. Figures for a low-income district of Mexico City show a 36% lower prevalence than for Mexican Americans in the USA. Prevalence in Brazil is approximately 7% in subjects aged 30-69 years. Black Americans have a relatively high prevalence of NIDDM, though not as high as the Mexican Americans. There is evidence that complications of diabetes may vary between populations, and that they may be particularly severe in Mexican Americans, and higher in black than in white Americans. The extent to which these differences relate to access to health care and treatment remains to be clarified. PMID- 1299076 TI - Recent developments in diabetes epidemiology in Europe. AB - Recent developments in diabetes epidemiology in Europe have included the completion of the European Community sponsored Concerted Action on the Epidemiology and Prevention of Diabetes (Eurodiab), further studies of diabetes and coronary heart disease prevalence in ethnic minority groups in the United Kingdom, and studies of the effect of poor fetal and early post-natal nutrition on the risk of developing non-insulin dependent diabetes (NIDDM). The EURODIAB Concerted Action Programme has provided valuable new information on the incidence of insulin-dependent diabetes mellitus (IDDM) throughout Europe and has drawn attention to an unexpectedly high incidence in Sardinia. In the EURODIAB IDDM complications study, the prevalence of both large- and small-vessel complications of diabetes has been examined, using standardized methods, in 3,279 IDDM patients from 31 centres throughout Europe. The data on risk factors for complications obtained from this study will have significant health policy implications for diabetes in Europe which will be utilized by the current St. Vincent Declaration Action Programme for Diabetes Care and Research in Europe. In another part of the EURODIAB Concerted Action Programme, important information has been obtained on the validity of routinely-collected diabetes health information, such as mortality statistics based on death certificates, and estimates of diabetes prevalence obtained from drug-utilization data. PMID- 1299077 TI - Diabetes in the eastern Mediterranean region. AB - Socioeconomic development and changes in lifestyles have been accompanied by the emergence of diabetes as a major problem in Eastern Mediterranean countries, but reliable epidemiological data are still scarce and comparability is generally poor. For non-insulin-dependent diabetes (NIDDM) in adults, risk is higher in urban than in rural subjects, and in all populations prevalence increases with advancing age. Whereas several surveys have reported prevalence of the order of 5%, a recent national survey in Oman, which used the full WHO criteria for diagnosis, based upon the 2 hour blood glucose concentration after a 75 g oral glucose load in all subjects, reported a prevalence of diabetes of 10% in those aged 20 years and over. A further 8% of men and 13% of women had impaired glucose tolerance (IGT). Insulin-dependent diabetes (IDDM) was reported to be considerably rarer in Kuwait than in Europe and North America, but some more recent data suggest variability in frequency within the region. IDDM is frequently accompanied by ketoacidosis at diagnosis. For NIDDM, 75% of cases are associated with obesity. Long-term complications appear to occur to the same extent as in Western countries. A recent WHO Task Force meeting has set goals and targets for diabetes prevention and control within the Eastern Mediterranean Region. PMID- 1299078 TI - A model protocol for a diabetes and other noncommunicable disease field survey. AB - Field surveys of diabetes and other noncommunicable diseases and their risk factors are increasingly being performed in both developed and developing countries. Although individual priorities and circumstances will influence survey design, a model survey manual and protocol is described which might assist investigators in formulating plans and preparing manuals for their own surveys. The model presented has been successfully used in developing countries, for both rural and urban communities, over more than a decade. It describes examples of survey objectives, and gives specific details of survey procedures and measurement techniques which may be utilized. It contains sufficient flexibility to allow its adaptation to local circumstances. PMID- 1299079 TI - [Diagnostic and therapeutic problems in HELLP syndrome]. AB - The HELLP syndrome is a severe and life-threatening complication of preeclampsia. Despite obstetricians are more aware of this syndrome maternal and perinatal mortality could not be reduced during the last years. The diagnostic problems of the HELLP syndrome are early detection of the disease, problems concerning differential diagnosis to other diseases with similar symptoms, and the different definition of the HELLP syndrome itself. For early detection of hemolysis determination of serum haptoglobin should be included in laboratory screening methods. Manifestation of DIG is not a principal sign of the HELLP syndrome but reflects a secondary pathophysiological process of the primary disease. Therefore administration of heparin and antithrombin III is not indicated and may lead to induction or amplification of life-threatening bleedings in these cases. Conservative approaches have shown to improve the fetal and maternal condition in individual cases, however, termination of pregnancy is the only definitive cure for patients with HELLP-syndrome. With respect to our perinatal results (n = 84) immediate delivery, predominantly by caesarean section, is recommended after diagnosis has been confirmed. PMID- 1299080 TI - [Experiences with HELLP syndrome]. AB - Between 1988 and 1991 thirty-nine pregnant women suffering from HELLP-Syndrome were treated in our hospital. A retrospective analysis of clinical course and of the changes in the relevant laboratory values was performed. The incidence of the HELLP-Syndrome at Freiburg University Hospital was 0.85% for all pregnancies or 17% of the patients with toxaemia. 90% of the women were primipara, there was no prevalence of a certain group. The clinical course was characterized by the perseverance of symptoms for more than two weeks in 18% of the cases and a perinatal mortality of 25%, the latter mainly due to prematurity of the infants. This suggests that perinatal mortality due to respiratory distress syndrome can be reduced by conservative and expectative management of these patients. However on the other side a high rate of caesarean sections (77%) and sometimes even induced abortions were necessary to avoid maternal mortality and severe pre-or postpartal complications for these women. PMID- 1299081 TI - [Morphologic placenta findings in clinico-serologically verified and suspected rubella infection in the 2d half of pregnancy]. AB - Rubeola is the congenital infection with the highest rate of embryonal damage. The hematogenous transplacental way of infection also causes morphological changes at the vessels of the placental villi. We examined 38 placentas from up to the 44th week of gestation and the fetus and children belonging to them. We regarded the clinical and serological findings. 6 out of 16 placentas from up to the 18th week of gestation (37.5%) showed endangitis obliterans. Two cases showed changes of the lenses. (Group I). In 10 out of 12 cases from the 19th to the 36th week of gestation (Group II) we found morphological changes in the vessels of the placental villi. The children belonging to them showed nonspecific malformations. From the 37th week of gestation (Group III) half of the placentas was histologically conspicuous. The children did not show malformations specific for rubeola. We refer to the possibilities and limitations of performing light microscopic diagnosis in placenta when there is the suspicion of rubeola infection, intrauterine death of the fetus and postnatal delay of the child's development. PMID- 1299082 TI - [Activity of ATP-dependent protease and steroid metabolism in the human placenta]. AB - Placenta play the important role of nourishment of fetus and for the regulation of fetal and maternal steroid metabolism. Steroid metabolism is synthesized in mitochondria and levels of enzymes in steroid metabolism are regulated by the rate of synthesis and degradation of these enzymes. Therefore, we studied protease in human placental mitochondria to clarify regulation mechanism of steroid-synthesizing enzymes. 50 micrograms of human early and term placenta homogenate, proteins were analyzed by immunoblotting technique after SDS polyacrylamid gel electrophoresis. ATP-dependent protease was detected using antiserum raised against purified bovine adrenocortical ATP-dependent protease and avidin-biotin complex method. ATP-dependent protease activity was assayed using 14C-Caseins a substrate. Five cell fractions of homogenate placenta were electrophorated and antibody-stained using ATP-dependent protease, cytochrome P 450 scc and adrenodoxin antibody after the blotting, and the quantity was analyzed by the densitometry and the method of De Douve. We had the following results: 1) ATP dependent protease is present in human placenta and localized in mitochondria. 2) ATP dependent protease decomposes adrenodoxin reductase in human placenta. 3) ATP dependent protease present in almost same consistent in early and term placenta and there is no significant difference. It is suggested as follows that the ATP dependent protease in human placenta participates in the regulation of steroid hormone through the metabolism of steroid synthetic enzyme. PMID- 1299083 TI - [Doppler ultrasound in monitoring twin pregnancies with early discordant growth]. AB - Early growth retardation in one twin is complicated by a high fetal mortality and morbidity. It is often very difficult to determine the optimum time of delivery in regard to placental insufficiency and prematurity. We report of two cases in which doppler velocimetry was a helpful method in monitoring those pregnancies at high risk. A growth retardation of three weeks was found in one child of a twin pregnancy at 17 weeks of gestation. Doppler velocimetry at 23 weeks showed a reverse flow and centralisation and the child died at 27 weeks. The other twin then also developed pathologic flow patterns and had to be delivered by cesarean section. In the second patient, pregnancy could be continued in spite of a growth retardation of three weeks in one child at 15 weeks and an additional decrease in the growth rate of both children from 30 weeks onwards. Cesarean section had to be performed at 34 weeks because of premature rupture of membranes. PMID- 1299084 TI - [Umbilical blood flow indices in smoking women]. AB - A collective of 154 pregnant women, who smoked at least 5 cigarettes a day was examined by doppler ultrasound. Measurements were taken at the two ends of the umbilical cord. The results had been compared to the physiological constellation of the resistance indices. Elevation of the PI was mainly to be registrated at the fetal abdominal insertion of the umbilical vessels. It seems to be dependent on the duration and amount of smoking. There was no correlation to be found to the fetal outcome. PMID- 1299085 TI - [Vaginal ultrasound in puerperium. Cervix and lower uterine segment on the 1st p. p. day and uterus 6 weeks post partum]. AB - In this study it was tried to demonstrate the involution of the puerperal uterus vaginosonographically. A collective of 54 patients with uncomplicated delivery and afebrile, inconspicuous puerperium was vaginosonographically examined on the 1st day postpartum and also 6 weeks post partum. To describe the uterus in its whole entity on the 1st day post partum an abdominal sonography was carried out too. The vaginosonographic examinations showed on the 1st day post partum an average cervical length of 40.7 +/- 8.4 mm, a width of 31.2 +/- 4.0 mm and an internal os of 5.6 +/- 3.0 mm. The width of the lower uterine segment was 15.7 +/ 7.7 mm. The control examination after 6 weeks result in a cervical length of 31.2 +/- 4.0 mm, a width of 28.2 +/- 3.9 mm and an internal os of 3.1 +/- 1.1 mm. The reformation of cervix occurs rapidly and can be seen even on the first day post partum. PMID- 1299086 TI - [Detection of toxoplasma-specific IgA and IgM antibodies in serum samples of adults with acquired toxoplasma infection]. AB - In a study of persons with and without toxoplasmosis, IgA-ISAGA (immunoglobulin A immunosorbent agglutination assay) was found to be specific. However, serum samples from subjects recently infected wtih toxoplasma were less reliable than the DNR test (IgM-ISAGA by the original method, 1981) and the IgM-IIFT. On the other hand, some serum samples from persons infected for up to a year or longer were IgA-positive. The IgA-ISAGA should therefore not be included in serodiagnosis in pregnancy as a substitute for IgM-ISAGA or IgM-IIFT, but, if at all, in addition to them. PMID- 1299087 TI - [Asymptomatic ablatio placentae]. AB - A 34 years old woman was admitted to our hospital with a retroplacental hematoma of more than 50% of placental area. It was diagnosed by routine pregnancy screening. The patient had no pain, bleeding or other clinical symptoms. 24 hours after inducing fetal lung maturation by betamethasone delivery was terminated by caesarean section in the 32nd week of gestation. Though the diagnose was confirmed by operation there was no influence of fetal outcome. The management of symptomless ablatio placentae is discussed by literature. Termination of pregnancy should be related the gestational age. PMID- 1299088 TI - [Night shift]. PMID- 1299089 TI - [Nurse chosen as "year's renovation master". Interview by Kaj Nyman]. PMID- 1299090 TI - [Christina leads housing project in Mozambique. Many nurses live in garages or sheds. Interview by Jan Thomasson]. PMID- 1299091 TI - [Project is important for care of patients. Interview by Jan Thomasson]. PMID- 1299092 TI - [Electric toilet seat will cause fewer occupational injuries. Interview by Jan Thomasson]. PMID- 1299093 TI - [Allow proposal for family physicians to mature!]. PMID- 1299094 TI - [Women's 10-kilometer run--a festival for both runners and nurses]. PMID- 1299095 TI - [Family physicians--a criticized proposal. Intensive professional activities to stop Stockholm's family physicians]. PMID- 1299096 TI - [Psychiatric reports are ready--"listen to the mentally disturbed!"]. PMID- 1299097 TI - [25th anniversary of the RSMH (National Association for Social and Mental Health): campaign organization has been growing in the living rooms]. PMID- 1299098 TI - [Annelie, laboratory assistant in health center--we work together without prestige for the patients' welfare. Interview by Nina Enstrom]. PMID- 1299099 TI - [Salaries dropped by 15 percent when local authority took over]. PMID- 1299100 TI - [The clinic is coming!]. PMID- 1299102 TI - [Pension outline needs discussion!]. PMID- 1299101 TI - [On the way to work on the West Bank--"suddenly we were stopped by Israeli settlers]. PMID- 1299103 TI - [Nurses look after children with leukemia: "we refuse to give up!"]. PMID- 1299104 TI - [Anemic and awkward dawdling puts Dala models in crisis]. PMID- 1299105 TI - 7th Symposium of the International Society for Invertebrate Neurobiology (ISIN), 23-28 June 1991, Tihany, Hungary. Proceedings. PMID- 1299106 TI - The role of membrane properties, synaptic input and electrical junction in determination of spike output of a pair of peptidergic neurons in the mollusc Lymnaea stagnalis. AB - The two electrotonically coupled peptidergic neurons, VD1 and RPD2 show in the isolated central nervous system (CNS) a patterned activity. The cells fire in almost perfect synchrony in CNS's derived from animals of moderate age, while in old animals disturbances in synchrony are observed. The firing pattern varies from beating to bursting. Isolated VD1's show a beating firing pattern, indicating that the cell possesses pacemaker properties, while the isolated RPD2 is almost always silent. Hybrid current/voltage clamp experiments show that in the intact CNS spike generation in the two cells is due to VD1, indicating that the pacemaker properties of VD1 constitute the main driving force for the firing rhythm of the two cell system. In low calcium/high magnesium solutions the rhythm is a beating one, while in solutions which do not suppress synaptic input, sometimes a bursting pattern is observed. The idea that the bursting pattern is due to synaptic modulation of these cells is corroborated by the observation that application of certain transmitters induces a very prominent burst of activity in these neurons. These bursts are very reminiscent of the bursts, observed in semi intact preparations, which are accompanied by penumostome movements. Increase in coupling resistance, which occurs at older age, is accompanied by irregularities in firing rhythm. Apparently the electrotonic junction is essential for the patterned output of the two cell system. PMID- 1299107 TI - Vanillin modulates the fast outward and calcium currents in Helix neurons. AB - A study was made to characterize the actions of vanillins on the resting membrane potential, action potential, membrane resistance and membrane ionic currents of identified Helix neurons. Two types of neurons can be classified according to the actions of vanillins. One type of neurons are the L and RPa 1-3 cells. Vanillin slightly depolarized these cells and moderately prolonged the action potential duration while increased the membrane resistance and initiated spontaneous spiking. Under voltage clamp, vanillin decreased the leak current, moderately suppressed the amplitude and decreased the time constant of decay of the A currents in dose-dependent way (Kd = 5mM, nH = 0.6). The delayed outward currents were not influenced by vanillins. Vanillin decreased the plateau potential of the Ca-spike in Na-free TEA solution and decreased the peak Ca-currents under voltage clamp. Second type of neurons are some pacemaker cells around the RPa burster. Vanillin caused a burst-like transformation of the beating activity followed by slowly developing presynaptic activation. The most characteristic action of vanillins on these cells is a long-lasting enhancement of the Ca-currents under voltage clamp. PMID- 1299108 TI - Peptidergic regulation of muscle movements in a prosobranch mollusc, Rapana thomasiana. AB - Peptidergic regulation of the contraction of radula muscles and the heart beat in a prosobranch mollusc, Rapana thomasiana was investigated. In the radula muscles, FMRFamide-related peptides were suggested to act on presynaptic sites to enhance their contraction elicited by nerve stimulation, possibly by increasing the release of a main transmitter. A catch-relaxing peptide (CARP) was demonstrated to depress the contraction by acting on postsynaptic sites. In the heart, FMRFamide enhanced the amplitude and frequency of the beat, whereas CARP depressed it. Immunohistochemical studies of the buccal ganglia have revealed that FMRFamide- and CARP-like immunoreactive neurons are distributed in the same region, indicating a possible coexistence of the both peptides. In the visceral ganglia, on the contrary, coexistence of FMRFamide and CARP was not observed. FMRFamide- and CARP-like immunoreactivities were also detected in the nerve fibers in the radula muscles and the atria. The present results show that FMRFamide- and CARP-like peptides are involved in the regulation of the contraction of radula muscles and the heart beat. PMID- 1299109 TI - The roles of local interneurons in the processing of olfactory information in the antennal lobes of the moth Manduca sexta. AB - The antennal lobe (AL) of the sphinx month Manduca sexta is characterized by a typically glomerular neuropil and two principal classes to neurons local interneurons and projection neurons. The somata of these neurons reside in defined neural cell-body groups in the AL, and the neurons exhibit characteristic patterns of innervation of the glomeruli. Evidence gathered to date indicates that individual antennal olfactory receptor-cell axons project to single glomeruli in the ipsilateral AL and make excitatory, apparently cholinergic synapses with neurites of AL neurons (usually local neurons) innervating the target glomeruli. Much has been learned about the physiology of the projection neurons, but only recently have the physiological properties and functions of the local interneurons been examined systematically through the use of intracellular recording and staining methods. Immunocytochemical studies have shown that most of the local interneurons contain GABA as well as one or more putative neuropeptides. Physiological, pharmacological, and biochemical experiments support the view that GABAergic local interneurons are responsible for inhibitory synaptic inputs to projection neurons that predominate in shaping the activity of projection neurons conveying synaptically processed olfactory information to higher-order centers in the protocerebrum. PMID- 1299110 TI - Diversity in tachykinin-like peptides in the insect brain. AB - When testing a large number of antisera against tachykinins of various vertebrates and one insect (the cockroach Leucophaea maderae) we found three distinct populations of tachykinin-immunoreactive neurons in the blowfly: (1) one recognized by antisera against substance P, (2) another by antisera against the frog peptide kassinin and (3) a third with antisera raised against the cockroach peptide Leucokinin I. As a comparison tests on the cockroach Leucophaea showed that only antisera against neurokinin A (NKA) and leucokinin I gave immunostaining, RIA and immunocytochemical displacement tests demonstrated that the each of the three listed types of antisera was specific for the corresponding antigenic peptide and showed virtually no cross reactivity with the other tachykinin peptides. By immunocytochemistry we have mapped the three populations of tachykinin-immunoreactive neurons in the blowfly CNS. Two constitute unique sets of interneurons that were previously not detected with other antisera, the third, recognized by antisera against substance P, is a subpopulation of the FMRFamide immunoreactive neurons. The leucokinin immunoreactive material in the blowfly seems to be chemically different from that in Leucophaea and also the sets of neurons immunolabeled in the two insect species are to some extent different. The preliminary results presented here indicate the presence of multiple forms of tachykinin-like peptides in the blowfly and that these are distinct from those in the cockroach. From the immunocytochemistry it appears that the insect tachykinins may be involved in a variety of regulatory functions in the CNS and in some cases possibly act as neurohormones. PMID- 1299111 TI - Evidence for octopaminergic nature of peripherally projecting DUM-cells, but not DUM-interneurons in locusts. AB - In locusts, a median neuroblast in each segmental ganglion gives rise to numerous unpaired progeny--the well known peripherally projecting dorsal-, occasionally ventral-, unpaired median (DUM-, resp. VUM-) neurones together with the lesser known DUM-interneurones 12. We examine the reputed octopaminergic nature of this nerve cell lineage using an anti-octopamine serum recently developed by M. Eckert and J. Rapus 7. This antiserum labels in each segmental ganglion numerous midline neurones, identifiable as DUM- and VUM-cells by their some sizes and positions, projections in DUM-tracts and characteristic T-junctions with bilaterally projecting axons. All octopamine immunoreactive DUM-, and VUM-neurones appear to project to peripheral nerves; their numbers correspond to the number of peripherally projecting DUM- and VUM-neurones identified so far in the examined ganglia. Presumptive DUM-interneurones, i.e. smaller somata interspersed between the peripherally projecting DUM-cells are not octopamine immunoreactive, but, confirming other studies 25, display GABA-like immunoreactivity. We thus suggest, that of the whole DUM-cell population in the examined ganglia, all and only peripherally projecting DUM-neurons are octopaminergic. PMID- 1299112 TI - The octopaminergic system within the ventral nerve cord of the American cockroach. AB - Octopamine-immunoreactive neurons within the ventral nerve cord of the cockroach, Periplaneta americana, were mapped with a new anti-octopamine serum. The specificity of this antiserum was demonstrated by dot blot immunoassay and by comparing the immunocytochemical staining patterns obtained after incubation with anti-dopamine and anti-octopamine serum. Putative octopaminergic dorsal and ventral unpaired median (DUM resp. VUM) neurons showed octopamine-like immunoreactivity in all ventral ganglia. The numbers of DUM cells in the mesothoracic, metathoracic and terminal ganglia of females correspond to those previously characterized by retrograde staining 19, 33, 34. It could be shown that besides segmentally projecting there are also intersegmentally projecting DUM neurons within the thoracic ganglia. In addition various, previously unknown, paired octopamine-ir cells were revealed in all ventral ganglia except the abdominal ganglia 2-5. PMID- 1299113 TI - Immunocytochemical and electrophysiological investigations of central neurones in the parasitic nematode Ascaris suum. AB - Here we report on preliminary investigations into the morphological, neurochemical and electrophysiological characteristics of central neurones in the parasitic nematode Ascaris suum. The neurones do not display all or none action potentials and apparently have low resting membrane potentials. Neurones have been shown to respond to acetylcholine. Immunoreactivity to a diverse range of neuropeptides has been demonstrated. PMID- 1299114 TI - Immunohistochemical study of the nervous system in earthworm (Lumbricus terrestris L.). AB - In the present work it we describe serotonin, noradrenaline, proctolin, neuropeptide Y, substance P, and calcitonin gene related peptide immunoreactive structures in earthworm. A few large serotonin immunoreactive perikarya are located in brain and in the stomatogasric ganglia and many of them in the segmental ganglia. A serotonin immunoreactive fiber plexus can be seen beneath the epithelium of the body wall, both the sensory papillae and chaetae contain serotonin immunoreactive elements. Some of the sensory cells are serotonin immunoreactive, too. A serotonin immunoreactive network can ben found in the enteric network of the fore- and mid-gut. Only a few noradrenaline immunoreactive cells are observed in the caudal part of the brain, while their number in the segmental ganglia is high. Proctolin-, and substance P immunoreactive cells are small and numerous in the brain without any preference in their location. Such nerve cells are widely distributed in the ganglia of the stomatogastric system, in the subesophageal and in segmental ganglia. Many surface epithelial (probably sensory) cells are proctolin immunoreactive. Substance P immunoreactive nerve cells can also be located in the entire length of the enteric plexus together with substance P immunoreactive fibers. No neuropeptide Y- or calcitonin gene related peptide immunoreactive structures can be seen in the brain. A relative small number of neuropeptide Y- and calcitonin gene related peptide immunoreactive perikarya, and a rich network of neuropeptide Y- and calcitonin gene related peptide immunoreactive fibers can be detected in the subesophageal ganglion. According to preliminary studies, neuropeptide Y is probably co localized with serotonin. PMID- 1299115 TI - Sensory receptors in the head of Stenostomum leucops. I. Presumptive photoreceptors. AB - General body sensitivity to light is present in Stenostomum leucops, expressed as increased activity and locomotion of resting animals by exposure to light. The sensory structures involved have not been identified so far. The head of S. leucops bears sensory cells in the ciliary pits, along the epithelium and in connection to the brain lobes. Two types of presumptive photoreceptor, quite distinct from eyespots, are found. The first type, a pair of ciliary lamellate bodies, is found on both sides of the worm between the ciliary pits and the anterior brain lobes. Both cells contain an internally ciliated vacuole. The sparse lamellae are derived from membranes of more than 20 milia, most of them consisting of a typical 9 + 2 axoneme pattern. The cells are connected to brain ganglia by nerve fibres, but there are no connections to the surface. No pigment cups are observed, either. The second type, two cells with light-refracting bodies, is observed more posteriorly, near the dorsal surface and in close nerve connection to the posterior brain lobes. Both cells contain numerous (20-30) refractile, round or ovoid granules of various sizes. They form a cup-shaped structure to one side of the cell, the concave surface directing forward. The granules resemble lipid spheres under the electron microscope. In addition to comparable similarities with presumed photoreceptors in other platyhelminths, the photoreceptive function of the ciliary lamellate bodies and light-refracting bodies was tested using tritiated thymidine ([3H]T) vitamin-A autoradiography. No specific labelling, however, was observed in these cells nor in other sensory cells in S. leucops. PMID- 1299116 TI - Immunoreactive cytokines in Mytilus edulis nervous and immune interactions. AB - We review evidence that an immune and nervous system linkage exists in invertebrates similar to that shown in vertebrates. Immunoreactive cytokines appear to play a role in this interaction. We have demonstrated that M. edulis, a marine bivalve mollusc, reacts to the vertebrate monokines interleukin-1, -6 and TNF. We have also demonstrated endogenous immunoreactive interleukin-1, -6 and tumour necrosis factor in M. edulis hemolymph, immunocytes and pedal ganglia. Our findings suggest an important common signalling mechanism that has been conserved over 500 million years of evolution. PMID- 1299117 TI - Soluble and membrane-bound Met-enkephalin degrading peptidases in Mytilus edulis hemolymph. AB - Recent reports have provided strong evidence indicating that Met-enkephalin is serving as a neuroimmune modulator. It acts as a bidirectional signal molecule in transmitting message between the endocrine system and the immune cells in the circulating fluid. In this study, we investigated peptidases which are capable of degrading Met-enkephalin in the hemolymph fluid and hemocyte membrane. Our results showed that aminopeptidase is present at a high level in the fluid and a low level in the membrane. Carboxypeptidase is not present in the fluid but it is present at a level higher than that of aminopeptidase in the membrane. Either ACE or neutral endopeptidase is also present in the hemolymph fluid and hemocyte membrane. Functional role of these peptidases in the overall scheme of the neuroimmune mechanism is currently under investigation. PMID- 1299118 TI - Proopiomelanocortin-derived peptides as tools of immune evasion for the human trematode Schistosoma mansoni. AB - Schistosomes are digenetic trematodes which share their life cycle between a definitive (vertebrate) and an intermediate (invertebrate) host. Their survival is highly dependent on their ability to reduce significantly the efficiency of the host defences. We have previously demonstrated the presence of POMC derived peptides (ACTH, alpha-MSH, beta-endorphin) in all stages of Schistosoma mansoni life cycle. Given the immunomodulatory properties of these peptides in vertebrates and invertebrates it has been postulated that they might be implicated in parasite immune evasion. We report the release of these neuropeptides during the cycle, associated with the inhibition by these peptides of the locomotory activity of immunocytes from both hosts, the hamster Mesocricetus auratus and the freshwater snail B. glabrata. The implication of these common signals in this new strategy of parasite adaptation is discussed. PMID- 1299119 TI - Cytotoxicity and cell death: studies on molluscan cells and evolutionary considerations. AB - In a previous study we demonstrated the presence of NK-like activity in the mollusc Planorbarius corneus. This activity can be ascribed to round hemocytes that have a morphology similar to that of vertebrate lymphocytes. We show here that this NK-like cytotoxicity is evident in serum-free culture medium. Moreover, the type of death induced by molluscan effector cells on their targets is probably similar to that induced by vertebrate effector cells, i.e. apoptosis or programmed cell death, as assessed by the protective effect exerted by 3 aminobenzamide when both types of effector cells were used. PMID- 1299120 TI - Insect motion perception. AB - The first step in this work of reconstruction of a theory of insect vision was to demonstrate that visual behaviour relies on scanning by self-motion and apparently involves measurement of angular velocities of contrasts moving across the eye. The next step was to demonstrate that parallax is also significant as a way of segmenting the visual scene into separate objects. There followed a series of experiments to rule out the existing theory that motion perception depends on autocorrelation, and at the same time an alternative theory was developed. The new theory assumes that at the level of the optic medulla there are numerous parallel channels on each visual axis, representing different neurons, all looking out for their specific combination of signals. The combinations are formed by positive, negative or no-change temporal contrasts at two adjacent visual axes at two successive times, forming 3(4) = 81 possible templates. Simulation of this highly parallel system shows that it can represent the moving image in a compact form that would be adequate to explain what is known for motion and form vision (but not colour vision) in insects. Form, like colour, would be seen as the ratio of numbers of responses of particular templates, in the same way that colours are seen as ratios of responses of receptors for different wavelengths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299121 TI - Behavioral switching of biting and of directed head turning in Aplysia: explorations using neural network models. PMID- 1299122 TI - Patterns of neural and behavioral activity in freely-moving Navanax inermis (Mollusca; Opisthobranchia). AB - As part of an ongoing neuroethological study of complex behavior in the opisthobranch mollusc, Navanax inermis, I have extended the available gross anatomical descriptions and used cuff electrodes to obtain chronic recordings from whole nerves or connectives. The major anatomical findings concern a) finer branches of the pedal nerves, particularly P3C P4 and P5; b) the distribution of nerves from the abdominal and subintestinal ganglia; and c) a possible neurohaemal area of the supraintestinal ganglion. With cuff electrodes it has been possible to get good quality recordings (often with spikes in the mv range) during the full repertoire of sexual, predatory and cannibalistic behaviors. The high degree of cryptic neural activity and the fact that in Navanax behaviors are not mutually exclusive, make it difficult to identify one-to-one correspondences between behaviors and neural patterns, However, there is an apparent correlation between the activity of a very large unit(s) on P5 and an exploratory behavior, the Face-Down head posture when it is directed at the substrate rather than prey, or a conspecific. PMID- 1299123 TI - Cerebral and buccal neurons involved in buccal motor pattern generation in Achatina fulica. AB - In the African giant snail, Achatina fulica, two pairs of cerebral neurons, v CDNs and Cls, and ten pairs of buccal neurons, Bls-B10s, were identified. B1-B6 and B10 were the excitatory motoneurons of buccal muscles. B7 and B8 innervated salivary ducts and B9 extended its axons to the cerebral ganglia although their functions were not clear yet. Serotonergic v-CDN exerted excitatory effects on various neurons in the buccal ganglia and had modulatory effects on buccal muscles. When v-CDN, Cl or B1 was continuously fired, each one could initiate and maintain the rhythmic motor activity (RMA) in the buccal ganglia of reduced preparation. Taste stimulation of the lip often elicited RMA. Nevertheless, v-CDN and B1 were not always excited by taste stimuli, and they appeared not to be critical elements in the generation of feeding rhythm. In contrast, Cl responded to taste stimuli with burst of spikes. Thus, C1 may play a role in taste-induced rhythm generation in intact animal. PMID- 1299124 TI - Mating behavior in the pulmonate small melampus: can regeneration restore function? AB - Previous anatomical observations have established that the penial complex of adult Melampus bidentatus is specifically reinnervated and that the penial complex itself can regenerate. This review describes experiments to determine whether a reinnervated penial complex and a regenerated penial complex can function in mating. The snails are not self-fertile, so the ability to transfer sperm, evaluated by production of fertile eggs, was the test of successful regeneration. Snails with nerve transections produced fertile eggs within the time-span expected for axonal regeneration to the target organ. Penial complex ablation interfered with sperm transfer for two egg-laying cycles but fertile eggs were laid within a time-span consistent with regeneration of a penial complex. PMID- 1299125 TI - Heavy metal induced behaviour modulation in mussels: possible neural correlates. AB - Filtering behaviour of bivalves can be monitored by recording the contraction and relaxation of the adductor muscles, which maintain the filtering activity by closing and opening of the shells having rhythmic and periodic pattern with a time scale of several minutes and hours. Heavy metals (Cu2+, Hg2+, Cd2+, Pb2+, Zn2+) applied into the water for one week cause a clear cut alteration in the adductor's activity characterized in general by changing of the duration of activity and rest. Threshold concentrations affecting the animal's behaviour were 0.005; 0.01 0.05; 0.1 and 10.0 mg/l, respectively. With increasing concentration the duration of activity could be reduced up to 10-20 per cent of the control at application of Cu2+, Hg2+ and Cd2+. Rest periods were also influenced by heavy metals. Wash-out in most cases restored the original activity, sometimes a reverse effect was observed. Since heavy metals, if present in the water, cause reduction of the level of 5HT and DA in the ganglia of mussels and they modulate the chemical sensitivity of molluscan neurons and influence the permeability of various ionic channels, it is suggested that heavy metal ions affect directly both transmitter metabolism and membrane excitability and this way alterations of basic neural mechanisms are responsible in the observed modulation of mussels' behaviour. PMID- 1299126 TI - The Aplysia gill-withdrawal reflex revisited: components of the network. AB - Attempts to understand how changes at identified synapses contribute to the behavioral changes that constitute learning in the GWR have been complicated by the complexity of gill innervation. In addition to the well-studied circuit between siphon sensory neurons and identified gill motor neurons of the PVG, both PNS and as yet unidentified CNS pathways are also involved in the control of gill movement. In this study we combine an anatomical study of the PNS with physiological and behavioral analyses of the CNS's contribution to the GWR. We tested the possibility that altering the activity of an identified gill motor neuron is sufficient to alter the GWR. The results show that altering activity of GMNs has no demonstrable effect on the GWR in the suppressed behavioral state. Furthermore, activity in identified MNs may vary in response to a uniform stimulus and is not a good predictor of gill behavior. Immunohistochemical staining in gill and siphon showed discrete and well localized serotonin and SCPB like reactivity. This is the first report of serotonin and SCPB-like immunoreactivity in the PNS of Aplysia siphon. PMID- 1299128 TI - The respiratory central pattern generator of Lymnaea. AB - We have recently described the respiratory behavior of a pulmonate mollusc, Lymnaea stagnalis, and identified relevant motor neurons and interneurons involved in this behavior. Three interneurons, namely right pedal dorsal 1 (R.Pe.D1), visceral dorsal 4 (V.D4) and Input 3 interneuron (Ip.3.I) comprise the central pattern generator (CPG). We demonstrate that appropriate connections exist between these interneurons and that they are sufficient to form the basis for the CPG. PMID- 1299127 TI - Dynamic changes in neuronal volume resulting from osmotic and sodium transport manipulations. AB - Electrophysiologic parameters such as input resistance and response to microperfusion of neurotransmitters vary under circumstances where neurons from isolated ganglia of Aplysia californica are subjected to either long-term (several hours) blockade of active sodium transport or to hypo- or hyperosmotic solutions. Since one of multiple possible events under these circumstances is neuronal volume changes, we have developed a system using cultured Aplysia neurons and confocal scanning laser microscopy to directly monitor cell volume when the osmolarity of the perfusing solution is altered and when sodium transport is blocked. Volume changes of greater than 30% were observed, accompanied by changes in surface area of greater than 15%. The volume increase secondary to sodium pump inhibition and hypotonic solutions and the volume decrease secondary to hypertonic solutions were reversible. Our results demonstrate that neuronal volume may change dramatically and raise the possibility that dynamic changes in neuronal cell volume may have physiological importance. PMID- 1299130 TI - Mating termination in the male cricket. AB - The study indicates that the male cricket Gryllus bimaculatus extrudes the spermatophore in response to mechanical stimulation of specialized sensilla in the cavity enclosed by the epiphallus and terminates mating as revealed by spermatophore protrusion. The spermatophore extrusion, however, needs an increase in body tonus during cavity hair stimulation which is produced by male's copulatory actions in response to key stimuli on the dorsum, epiproct and cerci. At the same time, male's sexual excitation raised by courtship facilitates spermatophore extrusion. This is the first demonstration that mating can be artificially switched off in male insects. PMID- 1299129 TI - The respiratory central pattern generator (CPG) of Lymnaea reconstructed in vitro. AB - We have recently developed a model system for testing the necessity, appropriateness and sufficiency of individual components of the respiratory central pattern generator (CPG) in Lymnaea stagnalis. In order to examine the intrinsic and network properties of the three CPG interneurons (R.Pe.D1, V.D4 and Ip.3.I), these cells were isolated and cultured in vitro. All of these cells exhibited extensive neurite outgrowth within 18-24 h of plating in conditioned medium. These isolated neurons maintained their intrinsic properties in culture and also formed specific synapses with each other similar to those observed in vivo. However, only when all three interneurons were plated together was it possible to initiate the alternating rhythm characteristic of the respiratory activity observed in semi-intact or isolated brain preparations. PMID- 1299131 TI - Structure, receptor cell arrangement and function of the auditory organs in the foreleg tibia of three bushcricket species. AB - Comparative physiological and morphological studies were carried out on the auditory receptor organs of the forelegs in three closely related tettigoniid species (Psorodonotus illyricus, Decticus albifrons and Decticus verrucivorus). Functional adaptations of the receptor organs to the carrier frequencies of the conspecific song were found. The proportions of low- to high-frequency receptor cells within the organs of the three species are clearly different. This proportion is large in Psorodonotus illyricus, smaller in Decticus albifrons, and smallest in Decticus verrucivorus. These proportions are responsible for the different "frequency weighting" found in the activity of the receptor populations of the organs. The physiology of the receptor cells of the three species have been correlated with the dimensions of the critical stimulus-transforming structures inside the organs. This leads to an explanation of the different frequency selectivity of the receptor cells. PMID- 1299132 TI - Effect of serotonin and opiate peptides on ion-currents of dialysed Helix neurons. AB - The effect of serotonin, Met- and Leu-enkephalin was studied on the dialysed neurons of Helix pomatia L. Both the Ca- and K-currents were modulated by the above agents. Two types of neurons could be distinguished by their response to serotonin in the case of the voltage activated Ca-current. One group responded by increasing the inward Ca-current, others by decreasing it. Met-enkephalin decreased the Ca-current on every studied neuron, while Leu-enkephalin had modulatory action to both directions. Opiate peptides and serotonin showed a dose dependent effect, but had different threshold concentrations. The peptides and serotonin also influenced the voltage activated transient and delayed K-currents. Serotonin increased the K-current, while Met-enkephalin decreased it, and Leu enkephalin could either decrease or increase it. The variations on the response to serotonin and the opiate peptides on non-identified dialysed neurons of Helix can be explained by the presence of different receptors on the neurons used. PMID- 1299133 TI - Epileptic activity as a tool in neurobiology. PMID- 1299134 TI - Regeneration of an interneuronal network in Helisoma: re-establishment of synaptic contacts. AB - We have identified a network of three interneurons located in the central ring ganglia of Helisoma. Two of these interneurons, designated Left Pedal Dorsal 1 (LPeD1) and Right Pedal Dorsal 1 (RPeD1), are the largest neurons of the pedal ganglia and appear to contain dopamine and serotonin, respectively. A third interneuron, identified as Visceral Dorsal 4 (VD4), is a small FMRFamide immunoreactive cell located on the dorsal surface of the visceral ganglion. Monosynaptic chemical connections exist between all these interneurons. For instance, a reciprocal inhibitory connection exists between LPeD1 and RPeD1, whereas VD4 has inhibitory effects on both LPeD1 and RPeD1. Furthermore, LPeD1, but not RPeD1, has an excitatory connection with VD4. We demonstrate that following axotomy these interneurons not only regenerate their axons but re establish their appropriate synaptic connections. PMID- 1299135 TI - [Effects of liensinine on haemodynamics in rats and the physiologic properties of isolated rabbit atria]. AB - Liensinine(Lien), an alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, has been shown to have anti-arrhythmic action, its mechanism may be related to blockade of Ca2+, Na+ influx. Lien 3 mg/kg i.v. may temporarily inhibit all parameters of haemodynamics in anesthetized or pithed rats. The inhibitory effects on LVP, +dp/dtmax and SAP in anesthetized rats are slightly stronger than those of quinidine (Qui) 3 mg/kg. Lien 1-30 mg/kg dose-dependently produced these actions. Lien and Qui 12 mg/kg lowered LVP, +dp/dtmax and SAP by 33%, 37%, 29% and 9%, 12%, 9% respectively. While both of them inhibited the other parameters of haemodynamics with nearly equal degrees. The degrees of inhibitory effect of Lien 12 mg/kg on all haemodynamic parameters nearly corresponded to these of verapamil 1 mg/kg. Lien 1-100 mumol/L reduced the contractile force of isolated left atria and the spontaneously beating rate of isolated right atria of rabbits in concentration-dependent manner. These results indicate that the properties of the effect of Lien on haemodynamics may be similar to those of verapamil and different from those of Qui. PMID- 1299136 TI - [The composition of phospholipid and biosynthesis of platelet-activating factor in earthworm (Eisenia foetida)]. AB - Platelet-activating factor (PAF) was for the first time confirmed to exist in a lower animal, earthworm (Eisenia foetida). It amounts to 10.7 +/- 6.1 pmol/g wet body weight, and varied seasonally. Phospholipid analysis revealed that 1-O-alkyl 2-acyl-sn-glycerophosphocholine, a stored form of PAF precursor, accounted for 61.4% of the choline glycerophospholipids. Two kinds of enzyme activities operating in PAF generation in mammalian cells were also detected from this species. The PAF level increased markedly under some injurious stimuli such as cutting and pricking. The results suggest that PAF may be a primary mediator involved in pathological and physiological reactions even in lower animal like earthworm. The findings also cast a new light on the mechanisms underlying the antihypertensive and other effects of the Chinese medicinal earthworm, pheretima. PMID- 1299138 TI - [Synthesis and biological activity of some Val(Ala)-Tyr and Val-Tyr-Tyr peptides]. AB - 15B2 and WF-10129, reported as potent angiotensin-converting enzyme inhibitors (ACEI), were used as lead compounds for design of novel ACEI. Some of Val-Tyr-Tyr and Val-Tyr peptides were synthesized and tested for ability to inhibit ACE in vitro and in Vivo. The most potent compound was found to be N-(1-benzoyl-1 carboxymethyl)-L-Alanyl-L-Tyrosine (II5, IC50 = 7.9 x 10(-10) mol/L) which was prepared by the addition of Ala-Tyr to benzoyl-acrylic acid in the presence of triethylamine. The structure-activity relationships were also discussed. PMID- 1299137 TI - [Experimental study of tumor directed therapy with gastric cancer monoclonal antibody-mitomycin conjugate combined with propranolol or angiotensin II]. AB - The effects of vasoactive agents propranolol hydrochloride and angiotensin (AT II) on improving the directed therapy of cancer with the use of conjugate of gastric cancer monoclonal antibody (3H11) and mitomycin C (MMC) were studied. The antibody activity of the conjugate (3H11-HSA-MMC) was retained with the molecular ratio of 1:2:60. In tests with tumor-bearing nude mice, the tumor inhibitory rate of the conjugate alone was found to be 50%, while in conjugate treated mice that also received propranolol or AT-II the tumor inhibitory rate were 79% and 60%, respectively. In tumor-bearing nude mice given 131I-3H11 both propranolol and AT II increased the tumor uptake of 131I-3H11. These results indicate that these vasoactive agents can change the tissue perfusion ratio via the effect on tumor blood vessels and increase the access of the conjugate to tumor, thereby, enhancing the effectiveness of tumor directed therapy with the use of conjugates. PMID- 1299139 TI - [Side chain cleavage of sterols by Mycobacterium sp. M12]. AB - A mutant strain of Mycobacterium sp. M12 was obtained. It can convert cholesterol. 3 beta-acetyl-cholesterol, sitosterol and 3 beta-acetyl-sitosterol to 4-androstane-3,17-dione (4-AD) (main product, the yield is 69%, 70%, 26% and 22% respectively) and 1,4-androstadiene-3,17-dione (ADD) (little amount). Optimum conditions for the side chain cleavage of cholesterol and 3 beta-acetyl cholesterol by Mycobacterium sp. M12 were studied. PMID- 1299140 TI - [Chemical structure of glutinic acid, a new diterpenoid from Caryopteris glutinosa]. AB - A new diterpenoid compound named glutinic acid had been isolated from Caryopteris glutinosa Rehd by liquid chromatography on Al2O3 and silica gel column. The structure of glutinic acid was elucidated on the basis of IR, UV, MS, H1-NMR, 13C NMR, DEPT and 13C-1H-COSY spectral analyses. PMID- 1299141 TI - [Structure determination of saponin IX and X from Dipsacus asper Wall]. AB - Two new triterpenoid glycosides (IX and X) were isolated from the ethanol extracts of the roots of Dipsacus asper Wall. Their structures were deduced as 3 O-[beta-D-xylopyranosyl (1-->4)-beta-D-glucopyranosyl(1-->4)] [alpha-L rhamnopyranosyl (1-->3)]-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1- >2)- alpha-arabinopyranosyl-hederagenin (IX) and 28-O-beta-D-glucopyranosyl(1- >6)- beta-D-glucopyranosyl ester of IX (X), based on spectral and chemical analysis. PMID- 1299142 TI - [Two new steroidal saponins from Allium macrostemon]. AB - Two new steroidal saponins, macrostemonoside A and D, were isolated from the bulbs of Allium macrostemon Bung (Chinese name as Xie bai), a Traditional Chinese Medicine used for the treatment of myocardial infarction. Their structures were established as tigogenin-3-O-beta-D-glucopyranosyl(1-->2) [beta-D glucopyranosyl(1-->3)1]-beta-D-glucopyranosyl(1-->4)-beta-D- galactopyranoside (1) and tigogenin-3-O-beta-D-glucopyranosyl(1-->2)[beta-D-glucopyranosyl (1- >3)(6-O-acetyl-beta-D-glucopyranosyl)] (1-->4)-beta-D-galactopyranoside (2) by spectral and chemical evidences. 1 showed remarkable inhibitory effect on rabbit platelet aggregation induced by ADP in vitro (IC50 = 0.065 mmol). PMID- 1299143 TI - [Studies on pharmacokinetics of 9-beta-D-arabinofuranosyl adenine nanocapsules]. AB - A method to determine the concentration of Ara-a in plasma by reversed phase high performance liquid chromatography is established. The method offers the advantage of rapid and simple preparation of plasma samples and sampling volumes as small as 0.5 ml. There is no need to extract Ara-A (adenine arabinoside) or to remove or modify sugar moieties to obtain samples of adequate separation. In pharmacokinetic studies, when amounts of clinical material are small and large numbers of assay are required, the present method is very useful. The calibration curve is linear for a wide range of concentration. The recovery is 87.5%. After a single dose of Ara-A-NC adenine arabinoside nanocapsules or Ara-A injection via intravenous administration in rabbits, the Ara-A concentration in plasma was determined by this method. The pharmaceutical parameters of Ara-A-NC and Ara-A injections were obtained by using PKBP-N1 program in NEC computer. The data obtained fitted an open two-compartment model well with two correlation coefficients more than 0.99. In mice given Ara-A injection a shorter elimination half-time (20.32 min), MRT (9.647 min) and a smaller AUC (233.4 micrograms.min.ml 1) were obtained compared with the group given Ara-A-NC injection. For the latter, the figures were 67.82 min, 156.7 min and 309.9 micrograms.min.ml-1, respectively. It can be concluded that NC can alter the pharmacokinetic behavior of Ara-A in mice significantly and keep the drug at a higher level and for a longer time. PMID- 1299144 TI - [Differential pulse voltammetric measurements of cholesterol based on its oxidation after adsorption at the mercury electrode]. AB - Cholesterol can be adsorbed on the surface of the static mercury drop electrode, and then oxidized during anodic potential scan. The stripping peak potential in differential pulse voltammetry is at -0.08 V in 0.1 mol/L K2HPO4-KH2PO4 buffer solution. The stripping current is linear with the concentration of cholesterol in the range of 10(-7)-10(-6) mol/L. The detection limit found is 8 x 10(-8) mol/L after a 5 min pre-concentration period. The adsorption and oxidation mechanisms of cholesterol at the mercury electrode were then explored. The experimental conditions for measuring free cholesterol in human sera were examined. PMID- 1299145 TI - [Studies on the TLC scanning determination of lignans in Diphylleia sinensis Li]. AB - A simple, sensitive and accurate method for the separation and determination of the lignans: podophylltoxone (I), isopicropodophyllone (II), picropodophyllone (III), dehydropodophyllotoxin (IV), picropodophyllin (V), podophyllotoxin (VI), 4'-demethylpodophyllotoxin (VII) and diphyllin (VIII) is described. The sample solution was applied at a point 1 cm from the bottom edge of the HPTLC silica gel plate (10 cm x 10 cm), dichloromethane-diethyl ether (4:1) was used as the developing solvent. The plate was saturated for 30 min and then developed twice for 9.5 cm using ascending technique. The plate was sprayed with 2.5% ammonium ceric sulphate--20% nitric acid and toasted for 15 min at 120 degrees C, then fumigated with ammonia solution for 20 min at room temperature to intensify the spot color. The spots were scanned with a Shimadzu CS-930 TLC scanner. The contents of eight lignans in Diphylleia sinensis was calculated by comparison with standards spotted on the same plate. The standard curves were linear in the range of 0.48-2.52 micrograms for the eight lignans. The method has been applied to the analysis of various samples and can be used for the quality control of Diphylleia sinensis, podophyllum and dysosma preparations used in clinic. PMID- 1299146 TI - [The Belgian Society of Urology]. PMID- 1299147 TI - [The history of urology in Brussels]. PMID- 1299148 TI - [History of urology in Belgium. Its origins]. PMID- 1299149 TI - [The history of urology in Flanders]. PMID- 1299151 TI - Seeing patients from a new perspective. PMID- 1299150 TI - [Urology in Liege]. PMID- 1299152 TI - [Exposure to low-frequency electromagnetic fields and pregnancy outcome: a review of the literature with particular attention to exposure to video terminals]. AB - Exposure to extremely low frequency electromagnetic field (EMF) is very common and concern about its harmful effects has been raised. Video display terminals (VDT) in the office are among the most important sources of exposure. Animal studies have shown adverse effects on reproduction, but the role of EMF in human reproduction is not clear. Twelve papers considering the effects of VDT and other EMF exposure on pregnancy outcome are reviewed. Concerning VDT exposure, the pooled OR for spontaneous abortion was 1.0 (95% Confidence Interval, CI, 0.9 1.0). There was no significative trend in risk with exposure intensity. No significative risk emerged for low birth weight nor for congenital malformations. Regarding other sources of EMF (electric blankets, heated waterbeds, ceiling cable electric heat and power lines), some studies have suggested that spontaneous abortion, growth retardation and congenital defects are more frequent during the coldest month of the year (when the exposure to these EMF would have been higher). However, data on the issue are scanty. PMID- 1299153 TI - [Transvaginal echography in the evaluation of the grade of myometrial invasion in locally advanced endometrial carcinoma]. AB - Neoplastic myometrial invasion is an important prognostic factor in local advanced endometrial carcinoma, conditioning therapeutic choice. In 34 patients with stage I and II endometrial carcinoma, the depth of myometrial invasion was evaluated by transvaginal sonography (TVS). In comparison with pathological findings, TVS showed an overall accuracy of 82.3% with a sensitivity of 82.6% and a specificity of 81.8%. The principal error was related to the underestimation of the lesion: negative predictive value of 49.2% vs positive predictive value of 90.4%. In conclusion, TVS is an accurate imaging method for staging of local advanced endometrial carcinoma. PMID- 1299155 TI - [350 years of surgery in Quebec]. PMID- 1299154 TI - [Homologous intrauterine insemination: our experience]. AB - Sixty-five couples with male infertility or unexplained infertility or infertility due to cervical factor underwent 156 cycles of homologue intrauterine insemination. The overall pregnancy rate was 16.5% with 2.4 mean value of insemination cycles for each couple. The highest pregnancy rate was observed in cases of cervical factor infertility. The mean age of patients who had pregnancy was 30 years (overall mean value 34 years) and the mean time of sterility was 3 years (overall mean value 4.4 years). PMID- 1299156 TI - [Scleroderma and esophageal reflux, surgical monitoring]. AB - Ten patients with documented scleroderma were assessed before and after antireflux operations over a twelve year period. The approach was through the left chest in 9 of 10 patients (7 short Nissen, 1 Collis Nissen, 1 Collis Belsey) and through the abdomen for 1 (vagotomy, antrectomy and Roux en Y). Clinically, 5 of 10 patients still mention episodes of heartburn. Dysphagia, which was present in 8 patients before the operation, has been replaced by a slow emptying impression in five. Endoscopically five patients had a columnar lined esophageal mucosa. Four more were considered to have ulcerative esophagitis and stricture which proved to be also Barrett's esophagus in the postoperative assessment. Three patients had preoperative 24 h pH assessment when the technique became available. Their postoperative control studies revealed persistent acid exposure but to a lesser degree. All ten patients had 24 h pH studies in their postoperative assessment and 5 out of 10 still show abnormal exposure to acid. Esophageal motility studies did not reveal significant changes to the hypomotility of the distal esophageal body and to the decreased tone of the Lower Esophageal Sphincter area. Both radiologically and using esophageal transit scintigrams the esophagus shows atony and poor emptying before the operation. Retention is increased following the creation of an antireflux technique at the esophagogastric junction. The success rate of antireflux operations in scleroderma patients is limited. The ideal procedure to use in this condition remains unclear. PMID- 1299157 TI - [The intermittent "warm" blood cardioplegia]. AB - Even today, a plethora of cardioplegic solutions are in clinical use. In the study presented here, sixty-six consecutive coronary bypass procedures received normothermic (37 degrees C) blood cardioplegia (NBC) intermittently. This group of patients was compared to an historical group of 68 patients having received cold crystalloid cardioplegia (CCC), and a second group of 41 patients having received cold blood (10 degrees C) cardioplegia (CBC). The number of patients, as well as their age, sex, functional class, ejection fraction and urgency of intervention were comparable between the three groups. The preoperative use of inotropic drugs was less prevalent in the normothermic blood cardioplegia group (NBC 24% v. CCC 52% and CBC 51%, p < 0.05), as was the use of a pacemaker (NBC 8% v. CCC 52% and CBC 51%, p < 0.02). Finally, the rates of myocardial infarction and mortality were comparable between the three groups. These results suggest that normothermic blood cardioplegia is efficient in reducing the demand in O2, by inducing the electromechanical arrest of the heart and, that intermittent normothermic blood cardioplegia can be safe and effective. PMID- 1299158 TI - [Salvage heart surgery after percutaneous mitral valvuloplasty]. AB - Percutaneous mitral valvuloplasty (PMV) for selected patients with symptomatic mitral stenosis (MS) has been proposed as a safe alternative to open mitral commissurotomy (OMC) or mitral valvular replacement (MVR). Among 146 consecutive patients undergoing PMV from March 1987 to April 1990, 18 (12%) needed urgent (8) or delayed (10) (average 7 days) corrective surgery following PMV. There were 15 women and 3 men, with a clinical incapacity class II (3) or III (15), and with an intermediate risk for PMV according to echo score (mean = 8). The indications for corrective surgery were: massive mitral regurgitation due to tearing of the anterior leaflet (6), cardiac perforations (left atrium in 2, left ventricle in 3), PMV technical failure (5), severe atrial shunting (2). Operative procedures included MVR (14), cardiac wound suturing only (3), OMC (1). Operative mortality (30 days) was 22% (4/18), equally distributed among the urgent and delayed group. The causes of postoperative death were hemorrhage (2), severe cerebral ischemia (1) and sudden death (1). Compared to operative mortality after OMC (0/17.0%) or MVR (1/32, 3.1%) as the initial treatment for MS during the same time period, cardiac operation after failed or complicated PMV carried a significantly higher mortality (p = 0.004). Therefore, optimal patient selection and aggressive corrective surgery are necessary to decrease the PMV related mortality and morbidity. PMID- 1299159 TI - [Angioscopy in peripheral vascular surgery]. AB - At Saint-Luc's Hospital of Montreal, between January 1, 1990 and February 1, 1991, 47 angioscopic procedures were done in 43 patients submitted to peripheral vascular reconstructions. The purpose of the study was to evaluate the role of angioscopy during those procedures. The operations were as follows: twenty femoropopliteal bypasses done with reversed saphenous vein, 15 done with in situ saphenous veins and 10 done with synthetic grafts. Two patients had popliteal embolectomies. Seventeen percent of the cases showed technical problems with the use of controlled angioscopy and were subsequently corrected. Three residual valves and one unsuspected venous stenosis were found in 15 in situ grafts, for a total of 27% correctible defects. In the reversed saphenous group, one case of venous sclerosis and one case of anastomotic stenosis were found for a total of 10%. For the synthetic grafts group we found an intimal flap distal to the anastomosis in one case (10%). Finally, we found a significant residual clot in one case (50%) after embolectomy. The technique of angioscopy is simple, the equipment reliable, and the learning period is short. Angioscopy is a very useful approach and should be readily available in the armamentarium of every vascular surgeon. PMID- 1299160 TI - [3-D study of the immediate effect of the Boston brace on the scoliotic lumbar spine]. AB - In order to study the immediate 3-D effect of the Boston brace on lumbar scoliosis, 31 adolescents with idiopathic scoliosis King type I or II had a 3-D computerised reconstruction of their deformity with and without the brace. Results demonstrate that the brace produces a distraction of the lumbar spine similar to that produced by the Harrington instrumentation by correcting the frontal deformity at the expense of a significant reduction of the physiological lumbar lordosis. No significant effect on rotation of the apical vertebra or "detorsion" of the spine could be measured. We feel that a orthosis that provides a real 3-D correction of the deformity has yet to be developed. PMID- 1299161 TI - [Cysts of the choledochus in children: experience of the Sainte-Justine hospital]. AB - Choledochal cyst remains a rare pathology in western countries. Over the past 15 years, 18 children were diagnosed with choledochal cyst at Hospital Sainte Justine. There were 14 girls and 4 boys with an average age of 7.4 years ranging from newborn to 15 years. Abdominal pain, jaundice and abdominal mass were present in 70%, 54% and 7% respectively. Only one patient, a 15 years old girl had all three symptoms. Abdominal ultrasonography was diagnostic in all cases and in two cases, a cystic dilatation was found in the antenatal ultrasonography. Transvesicular cholangiography was performed successfully in 11 patients and showed a detailed anatomy of the biliary tract preoperatively. Sixty-seven percent of the cysts were type I while 33% were type IV. A common channel was found in 43% of the cases. Sixteen patients underwent cyst excision followed by Roux en Y hepatico-jejunostomy, one patient with associated biliary atresia had a porto-enterostomy and one patient had a cysto-duodenostomy. The last patient had recurrent episodes of cholangitis and required reoperation while the others are doing well and free of infection. With the liberal use of ultrasonography, the diagnosis of choledochal cyst is being done earlier improving the long term prognosis. Transvesicular cholangiography is a very useful addition in the preoperative investigation of these patients. Roux en Y hepatico-jejunostomy was associated with minimal morbidity and mortality and gave excellent result. PMID- 1299162 TI - [Breast feeding after breast reduction]. AB - Few authors have addressed the feasibility of breast-feeding after a reduction mammaplasty. Nowadays, the majority of plastic surgeons perform breast reductions with techniques preserving the continuity of the nipple-areola complex with the retained breast tissue. These pedicle techniques should permit lactation as opposed to the free nipple grafting technique used earlier. To find out how many women nurse their children after a reduction mammaplasty, we reviewed 806 charts to identify 243 women having had a pedicle technique breast reduction, between 1967-1987, at the age of 15 to 35 years. These women were contacted and 98 of them were reached. Eighteen women had become pregnant after their surgery. They agreed to answer a questionnaire regarding their decision to nurse their children, the duration of breast-feeding and the difficulties encountered. Eight of eighteen mothers (45%) nursed their children up to 32 weeks (mean 11 weeks). Among them, 3 nursed for less than 3 weeks and 5 nursed from 3 to 32 weeks (mean 20 weeks). Only one mother had to supplement nursing with formula. Two mothers used mixed formula and breast-feeding when they returned to work. Ten of eighteen mothers (55%) did not breast-feed for the following reasons: 6 by personal choice, 2 due to premature delivery, one was advised that nursing was not feasible and one had no lactation. We believe that the nursing capacity of the breast is preserved after a breast reduction and that women should be encouraged to nurse their children. PMID- 1299163 TI - [Quality of life of patients after restorative surgery for cancer of the rectum]. AB - During the last decades surgeons have put a tremendous effort to perform low anterior resection (LAR) as a curative procedure for rectal cancer treated classically by abdomino-perineal resection (APR) and permanent colostomy. A psychological evaluation testing the multi-dimensional concept of quality of life was done in 32 patients (M = 21; F = 11) treated by APR and compared to 28 patients (M = 16; F = 12) treated by LAR. Patients were assessed for quality of life on the following dimensions: physical well-being, psychological well-being, dietary habits, surgical response, social concerns, body image, stress and marital adjustment. Using as covariables social support and time elapsed since surgery, a covariate analysis was used to determine the presence of group ans sex interaction. Patients with LAR had a better body image (p.001), dietary habits (p.003) and tolerance to stress (p.004). Better global quality of life (p.001), physical well being (p.001) and less surgical sequela (p.001) were found with LAR in women only. No significant difference was found on psychological well being, social concerns and marital adjustment in both surgical groups. PMID- 1299164 TI - [Endoscopic retrograde cholangiopancreatography in the context of cholecystectomy under celioscopy]. AB - This descriptive cohort study documents the results of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) in the perioperative period of laparoscopic cholecystectomy (LC). Of 630 consecutive patients undergoing LC, 83 (13.2%) sustained 96 ERCP, of which 65 were performed preoperatively (67.7%) and 31 postoperatively (32.3%). The common bile duct cannulation rate was 96.9% after the first attempt and 100% after the second in three patients. Common duct stones were found in 40 patients (6.3%) and three other anomalies were demonstrated ES was performed in 42 patients and 100% clearance of the common bile duct was achieved after 45 extraction procedures. Six patients (1%) were found at follow-up with unsuspected common duct stones and were all successfully treated with ES. At present time, the morbidity of ERCP and ES (7.2% and 11.9%) make them worthwhile adjuncts to perative cholangiography for the diagnosis and treatment of common bile duct stones found during the perioperative period of LC. PMID- 1299165 TI - [Murine surgical model for the study of cultured grafts]. AB - The objective of the study was to establish an animal model for in vivo studies of cultured cutaneous equivalents. The model on athymic mice that we already described (Lopez-Valle C.A. et al., Plast Reconstr Surg, 1992, 89, 139-143) satisfied the criteria of immobilization of the recipient site and physical stability of the graft, but still allowing complete movement freedom of the animal used. Nevertheless, this technique encountered two long term weaknesses; a) a significant grafted surface reduction caused by the wound contraction and b) the absence of a physical barrier between human and murin keratinocytes. We propose some modifications to this technique to correct both problems. Moreover, the implantation of polypropylene, instead of glass pellets, to generate granulation tissue on the recipient bed when needed, constitutes an easier method for both the surgeon and the animal. Finally, in order to minimize wound care, some modifications were made to the rodent cages. Immunohistological analyses of the biopsies, 21 days post-grafting, revealed a continuous basal membrane. This animal model allows in vivo studies on the behavior, cicatrization and immunology of human cultured skin equivalents. PMID- 1299166 TI - Specific allergen induced motility of peripheral blood mononuclear cells and polymorphonuclear leukocytes in insect sting allergy. AB - The motility of peripheral blood mononuclear cells (MNC) and polymorphonuclear (PMN) leukocytes from normal and bee venom allergic subjects was investigated by a modified Boyden micropore filter method. The study comprised MNC locomotion in bee venom and histamine gradients and PMN locomotion in bee venom and fMLP gradients. We demonstrated statistically significant increase in MNC and PMN motility towards bee venom in allergic patients group. This effect disappeared after the preincubation of MNC with anti-human IgE antibodies. We observed no such effect in PMN leukocytes. Increased MNC motility in histamine gradient was observed only in control subjects group. Similarly significant increase in PMN locomotion towards fMLP was found in both allergic and control subjects. The results here demonstrated suggest that a specific allergen might be a chemoattractant for peripheral blood MNC and PMN leukocytes from atopics and could be capable to induce non-infectious inflammatory reactions as a result of its interaction with these sensitive cells. PMID- 1299168 TI - HLA-DR antigens in children with mumps meningitis. AB - The frequency of HLA-DR antigens was studied in 54 patients with mumps meningitis, and in two control groups. The first control group comprised 333 randomly chosen subjects while the second group was composed of 46 subjects who have passed mumps without meningitis. The DR5 antigen was more frequent in patients than in the second control group with relative risk of 2.4 and significance at the level of p < 0.05. The p value became insignificant after the correction for the number of antigens investigated. PMID- 1299169 TI - Studies on immunity in mice immunized with outer membrane proteins of Hafnia. AB - Nonspecific protection induced in mice after administration outer membrane proteins of Hafnia alvei against infection with homologous and heterologous bacteria was transferred into other mice with lymphocytes isolated from spleens of mice immunized with outer membrane proteins. It was also found that mice sensitized with outer membrane proteins derived from H. alvei or with living bacteria induced in animals delayed hypersensitivity (DTH) in homologous and heterologous systems. The observed type of hypersensitivity was transferable to normal mice by lymphocytes obtained from donor animals which were previously sensitized with OMP. The experiments revealed that immunity induced with outer membrane proteins of Hafnia alvei is cell-mediated. PMID- 1299167 TI - Specific immunotherapy stimulates the binding of histamine H2 receptor antagonist by lymphocytes. AB - The binding of antagonists of histamine receptors H1 (promethazine) and H2 (ranitidine) by peripheral blood lymphocytes from pollinotics was determined before and after the course of immunotherapy. We found that lymphocytes from atopic subjects showed significant decrease in the binding of H2 receptor antagonist as compared to control subjects. Specific immunotherapy induced statistically significant increase in H2 receptor antagonist binding, which correlated with the improvement of clinical symptoms. PMID- 1299170 TI - Some biological properties of outer membrane proteins of Hafnia. AB - Outer membrane proteins (OMP) isolated from four antigenically different strains of Hafnia alvei were tested for the toxicity, pyrogenicity, ability to induce Shwartzman reaction as well as for their influence on the leukocyte system. LD50 doses for the studied preparations determined on inbred mice were 18, 20, 28 and 34 mg/kg. These differences in the toxicity of the preparations were reflected in manifestation of Shwartzman reaction; more toxic preparations induced strongest necrohemorrhagic changes at the site of injection. The OMP preparations injected intravenously to rabbits caused moderate increase of body temperature. They induced changes in the number of leukocytes in the animals comparable with those of other preparates of bacterial origin. PMID- 1299171 TI - Effect of outer membrane proteins from Shigella on humoral immunity induced in mice by SRBC. AB - Shigella flexneri outer membrane proteins (OMP) which had been earlier found to exert immunomodulatory effect on cell mediated immune response were also found to act as immunomodulator of the humoral immune response. Effects of OMP were investigated in the experiments in vitro and in vivo, where the level of humoral immune response, measured as the number of plaque-forming cells (PFC) to SRBC in the spleen was evaluated. We demonstrate that small doses of OMP (1-5 micrograms) stimulate, whereas higher doses (10-50 micrograms) suppress the humoral immunity. PMID- 1299172 TI - Fraction of spleen cells responsible for suppression of cellular immune response to SRBC in mice treated with outer membrane proteins of Shigella. AB - Effect of splenocytes isolated from mice immunized with suppressive dose of OMP from Shigella on delayed hypersensitivity, induced in mice with sheep red blood cells was investigated. Only the population of T lymphocytes was found to suppress the delayed hypersensitivity, as measured by the footpad reaction. The results suggest that OMP of Shigella are able to induce in the spleens of animals active T cells which are responsible for the suppression of cellular response induced by SRBC. PMID- 1299173 TI - In vitro cytostatic activity of some amino acid 4-N-substituted cytosines. AB - Cytotoxicity of 22 amino acid 4-N-substituted cytosine derivatives was studied on KB and HeLa human tissue cultures. A 4-N-(1H-2-oxo-4 pyrimidyl)-tryptamine with ED50 activity values of 0.145 x 10(-3) mole/l and ED0 = 0.4 x 10(-5) mole/l showed the highest cytotoxic activity and was qualified for further in vivo investigation. The secondary modification of tryptamine substituent seems to be a determining factor of the cytotoxic activity of 4-N-pyrimidinyl amino acids. The activity of the investigated compounds was inversely dependent on their solubility limited by the results of the solubility-activity relationship analysis. PMID- 1299174 TI - HLA-A, B, C, and DR gene and haplotype frequencies in 600 poles by a maximum likelihood method of gene counting. AB - A population sample of 600 healthy, unrelated persons was used for estimating HLA A, B, C and DR antigen, gene and haplotype frequencies. The Polish population is characterized by a high value of HLA-A10, B13, B27, DR1 and DR5 gene frequencies. Strong gametic associations between genes A1 and B8, A3 and B7, as well as between B8 and DR3, and B7 and DR2, typical for many European populations, are also present in the Polish population. PMID- 1299175 TI - The effect of thymic hormones (TFX) on lymphocyte subpopulations and proliferation after maximal physical effort. AB - The studies were performed on healthy well-trained cyclists. Maximal physical exercise was performed on a Monark bicycle ergometer according to individual schemes. Heart rate amounting to about 200 bts/min and oxygen consumption stabilization were considered as criteria for maximal physical exercise. In this study we have investigated the effect of short-term stimulation of conditioned sportsmen with thymic hormones and evaluated T cell subsets, DR antigen and transferrin receptor expression as well as mitogen-induced proliferation of lymphocytes before and after maximal physical effort. The results suggest that intensive physical exercise may be responsible for transient decrease of CD4/CD8 ratio and mitogen responsiveness, and increase of mononuclear cells number bearing HLA DR+ and CD71 antigens. These changes were modified by the treatment with thymic hormones. PMID- 1299177 TI - Oxidative metabolism of peripheral blood neutrophils in chronic renal failure on conservative and dialysis treatment. PMID- 1299176 TI - Antilymphocyte globulin with a small dose of cyclosporine A and prednisone as the induction of immunosuppression in renal allograft recipients. AB - In attempt to avoid a detrimental synergism between CsA and renal ischemia in the immediate postoperative period, ALG (425 lymphocytotoxic units/kg) with small doses of CsA (6-8 mg/kg) and P were applied as the initial immunosuppressive therapy in 14 recipients of cadaveric kidneys. ALG was administered for 5 to 14 days and 2 days before withdrawing ALG, Aza (2 mg/kg) was introduced. Results of this protocol were compared with those of 19 pts treated with CsA (12 mg/kg) and P. All the pts were followed for at least 12 months. The duration of posttransplant anuria was significantly reduced in the ALG/CsA/P group (p < 0.02). The sCr concentration after 12 months of observation was significantly lower (p < 0.05), no alterations in urinalysis were detected, the number of hypertensive pts was decreased. The acute rejection rates were equivalent in both groups, however 3 of 4 rejections in ALG/CsA/P group were resistant to steroids and occurred in pts with shortened period of ALG administration. The one year patient and graft survival in the ALG/CsA/P and control groups were respectively: 78.5%, 71.4% and 89.4%, 78.9%. Severe infectious complications in the group treated with ALG/CsA/P occurred in pts who were subsequently treated with OKT3. PMID- 1299179 TI - Nursing research targets into the twenty-first century: a national statement. PMID- 1299178 TI - ANF affiliation to ICN in doubt. PMID- 1299180 TI - Nurse and the law. When a person in Cas. faints. PMID- 1299181 TI - Fluconazole antifungal agent. PMID- 1299182 TI - Health reforms--lessons for us in NZ model. PMID- 1299183 TI - Inferior vena cava "birds nest" filters--2 year follow-up. AB - This study examines long term efficacy and saftey of "birds nest" filters (Cook), and the use of doppler ultrasound to assess patency. Of the seventeen "birds nest" filters inserted twelve were available for study. All patients were reviewed for evidence of recurrent pulmonary emboli or filter complication. Mean length of follow up was 10 months, (7 had follow up of > 12 months). Three have had further episodes of deep venous thrombosis, with probable recurrent pulmonary embolism in one. No patient had evidence of thrombosis of the inferior vena cava. No fracture or migration of the "birds nest" filters was found. Ten of the twelve filters studied with ultrasound could be visualized within the cava. In all, turbulent flow was detected with colour and duplex doppler study. We conclude that insertion and use of the "birds nest" filters is safe, with a high long term patency rate and few initial or long term complications. Doppler ultrasound is a simple and rapid method of assessing venous patency. PMID- 1299184 TI - Use of percutaneous transluminal balloon angioplasty to treat renovascular disease. AB - This is a retrospective study of the ability of percutaneous transluminal balloon angioplasty (PTA) to treat hypertension and renal impairment in patients with haemodynamically significant renal artery stenoses (those over 50%). Thirty-two patients underwent PTA procedure in a 4 year study period. Seventeen were male, 15 female, with an average age of 61 years. Thirty patients had atherosclerosis and 2 had fibromuscular hyperplasia (FMH) lesions. The procedure was technically unsuccessful in 28% of 37 arteries attempted, primarily in the > 80% stenosis group. The mean clinical follow-up period was 20 months. In those patients with technically successful PTAs, none was cured, with no change in the status of hypertension or medication required. Clinical improvement was seen in 37% (7 of 19) patients with atherosclerotic disease and who had PTA of significant unilateral lesions or of the haemodynamically significant side in cases of bilateral disease. Two patients with FMH lesions had improvement. Five patients with PTA of only one side in cases of significant bilateral disease gained no benefit. Nine patients with pre-existent renal insufficiency and technically successful PTAs had no improvement of renal function. No mortality or any significant morbidity resulted from the procedure. These results are more compatible with more recent than the earlier literature. PMID- 1299185 TI - Ultrasound, computed tomography and magnetic resonance in the investigation of iliopsoas compartment disease. AB - The authors reviewed the results of imaging studies performed in 30 patients with diseases involving the iliopsoas compartment (IPC) to assess the role of Ultrasound (US), Computed Tomography (CT) and Magnetic Resonance (MR) in the investigation of these deep seated and often clinically undetectable lesions. 16 (53%) patients had histologically proven benign or malignant IPC tumours with bacterial infection in 12 (40%) and haemorrhage into the IPC in 2 (7%). US correctly detected iliopsoas pathology in only 9 of 17 cases (53%) and was satisfactory only in limited situations, such as abscess formation in children and haemorrhage in haemophiliacs. CT was much more accurate (16/17, 94%) than US and correctly diagnosed 7 cases overlooked on US, while also offering greater information in 5 cases where both studies were abnormal. CT was particularly helpful for the detection of both abscess formation and calcification within mass lesion. MR was accurate in all 9 cases imaged, and was very helpful in the assessment of associated vertebral, disc or spinal canal involvement by tumour or infection. A review of the literature, and the results of this study, suggest that CT and MR often have complementary roles where IPC disease is known or suspected. The accuracy of US in IPC disease is limited, preferably being followed by CT or MR imaging. PMID- 1299186 TI - Selecting an MRI unit: a guide. PMID- 1299187 TI - Head injury: pseudodelta sign on CT. PMID- 1299188 TI - The bony crescent sign--a new sign of facial nerve schwannoma. AB - Schwannomas of the facial nerve are rare slowly growing lesions that have a predilection for the geniculate ganglion. Radiological evaluation is important in their diagnosis and in the assessment of their extent. In our series of 4 cases the facial nerve schwannoma was seen on high resolution CT as a soft tissue mass bounded anteriorly by a thin rim of bone. This bony crescent sign is a previously undescribed sign of facial nerve schwannoma which appears on the basis of this small series to be strongly indicative of the presence of this tumour. Schwannomas are relatively uncommon intracranial tumours. They most commonly involve the acoustic nerve followed in frequency by the trigeminal nerve. Other cranial nerves are rarely involved. Facial nerve schwannomas occurring within the petrous temporal bone are very rare. Their diagnosis may be missed prospectively even when appropriate CT scans are performed. Even in retrospect the site of abnormality may be difficult to identify, especially if there is an associated middle ear mass such as a cholesteatoma. Lesions occurring in the petrous area are all rare. The differential diagnosis includes cholesterol granuloma, epidermoid, carotid aneurysm and, very rarely, primary and secondary bone tumours. We describe a new sign associated with facial nerve schwannoma on CT, that of a bony crescent. Recognition of this sign makes those tumours arising in the region of the geniculate ganglion easy to diagnose prospectively. PMID- 1299189 TI - CT appearances of rounded atelectasis. AB - Five patients examined with CT had lesions fulfilling criteria for a diagnosis of rounded atelectasis (RA) and these were managed without biopsy. In three patients unsuspected contralateral lesions were identified as RA variants, and one of these was biopsied at thoracotomy and proved to be benign. All patients remain well at 6-22 months follow-up. We concur with recent reports that there is a spectrum of CT appearances of RA and that even atypical lesions seldom need further investigation. We also suggest that the appearances of some atypical lesions add support for the fibrosing theory of pathogenesis of RA. PMID- 1299190 TI - Traumatic rupture of the aorta. AB - In a series of 28 patients with suspected ruptured thoracic aorta, only three were shown to have sustained such an injury. To minimise the number of negative examination, the importance of optimising the initial radiological examination of the chest is discussed along with the importance of visualisation of the descending aorta. The signs that lead to the suspicion of rupture of the aorta are numerous and non specific and indicate some change in the mediastinum which could be significant in the given clinical context. This paper wishes to emphasise a negative sign, namely visibility of the descending aorta. PMID- 1299191 TI - Lung dose rate and interstitial pneumonitis in total body irradiation for bone marrow transplantation. AB - The effect of dose rate to the lungs and development of interstitial pneumonitis (IP) was evaluated in 114 bone marrow transplant patients receiving fractionated total body irradiation (TBI) (1200 rads TD in 6 fractions twice daily over 3 days) as part of their pre-conditioning regimen. The tumour dose (TD) was calculated as the mean lung dose as previously described (1). A 6MV linear accelerator at a mid-line dose rate of 7.5 rads/minute was used between March 1981 and June 1985 and a Co-60 source at 5 rads/minute thereafter. This resulted in a range of dose rates to the lung of between 6.9 and 8.9 rads/minute and 2.9 and 6.5 rads/minute respectively. In the majority of patients the aetiology of IP was investigated by lung biopsy with histology and culture. There was no statistically significant difference in the incidence of IP over the two sets of dose rates. Our study suggest that the incidence of IP using fractionated TBI is not influenced by dose rates below 8.9 rads per minute. PMID- 1299192 TI - Foetal radiation dose in radiotherapy for breast cancer. AB - Management of breast cancer during pregnancy is complicated by the high risks of abortion and foetal malformation from the use of radiotherapy and chemotherapy. A case of breast cancer during pregnancy, treated with radiotherapy, and the estimated foetal dose is reported. PMID- 1299193 TI - Technical report: fallopian tube recanalization facilitated by a hydrophillic glide wire. AB - Fallopian tube recanalization is now a well established radiological procedure (1). We describe a case in which the tubal obstruction was resistant to the standard technique of recanalization by the passage of a platinum tipped wire but in which we were able to achieve success with the aid of a hydrophillic "glide" wire (Radifocus angled tip, Terumo Corporation, Tokyo, Japan). PMID- 1299195 TI - Enterogenous cyst of the cervical spinal canal. AB - A case of an enterogenous cyst of the cervical spinal canal in an 18 year old man is presented, high-lighting the radiological findings. A brief overview is given of these rare cysts, together with their clinical and radiological features and associations. PMID- 1299194 TI - Percutaneous ultrasound guided cholecystostomy with double bubble catheter. AB - We have used a prototype double bubble cholecystostomy catheter in four very ill patients. This has been done under local anaesthetic using a Seldinger technique, ultrasound guidance, and a trans-peritoneal approach to the gallbladder. The catheter provides drainage, cholangiography, and is intended to allow instrumentation of the biliary tract at a later stage. PMID- 1299196 TI - Organo-axial volvulus of the sigmoid colon. AB - A 59 year old man presented with subacute abdominal distension and diarrhea. Plain radiographs and barium enema demonstrated organo-axial volvulus of the sigmoid colon. The radiologic, surgical, and pathologic findings are presented. The radiologic differences between organo-axial volvulus and the common mesentero axial volvulus of the sigmoid colon are discussed. PMID- 1299197 TI - Neoplastic involvement of the sacroiliac joint: MR and CT features. AB - The radiological findings in five patients with pelvic soft tissue neoplasms directly involving the sacroiliac joint, are described. All patients had Computed Tomography (CT) examinations, two of the patients also having Magnetic Resonance Imaging (MRI). The role of imaging in this uncommon entity is discussed as well as the importance of making this diagnosis, thereby excluding unilateral sacroiliitis. The therapeutic implications of this diagnosis relate to local neural involvement, especially the sciatic nerve, and the fact that involvement of the sacroiliac joint by tumors significantly compromises chances of a successful surgical outcome. The role of MR in this condition is not yet certain, but it may prove to be the method of choice in view of its excellent depiction of skeletal neoplasms. PMID- 1299198 TI - Assimilation of the atlas with associated syringomyelia and Chiari 1 malformation (Klippel-Feil type 2). AB - This case report describes an unusual congenital anomaly of the craniovertebral junction in a 14 year old male. Cervical radiographs showed the bony anomaly, while thin slice CT (with 2-D and 3-D reformations), MR imaging, and angiography were particularly useful in accurately assessing the bony, soft tissue and vascular anatomy, prior to and following surgery. PMID- 1299199 TI - Wegener's granulomatosis: parotid involvement and associated pancreatitis with C.T. findings. AB - Parotid enlargement is an uncommon physical sign and even less commonly the reason for referral for computerised tomography (CT) as the aetiology is usually self-evident. In cases referred for CT examination Wegener's granulomatosis should be considered, particularly if the pathology appears bilateral. This diagnosis may be confirmed by biopsy and/or supported by Anti-Neutrophil Cytoplasmic Antibody (ANCA) assay. A case of Wegener's granulomatosis with parotid gland involvement and temporally related pancreatitis with pseudocyst formation is reported. This is the second reported case of possible pancreatic involvement in Wegeners granulomatosis and approximately the tenth reported case of salivary gland involvement. PMID- 1299200 TI - Re: Nuclear medicine and diagnostic radiologists. PMID- 1299201 TI - Re: Waiting lists for radiation treatment. PMID- 1299202 TI - "How should a waiting list for treatment be managed?". PMID- 1299203 TI - Re: Film processing. PMID- 1299204 TI - Biological adaptation of the myocardium to a permanent change in loading conditions. AB - Cardiac hypertrophy due to permanent mechanical overloading is only one example among thousands of the general process of biological adaptation. The process is randomly governed and results in at least one thermodynamical benefit: to be adaptational and to induce several changes in gene expression. Some of these changes are detrimental, some can even be useless. The cascade of events which finally leads to a permanent modification of the genetic expression involves an initial signal, likely to be the stretch, a pathway which transducts the signal, and a transient change in genetic expression which transmits competence to the cell to be transformed. The permanent modifications occur at all cellular levels including the sarcomere, sarcolemma, energy metabolism, and extra-cellular matrix, but they are species-specific and differ in the ventricles and the atria. PMID- 1299205 TI - Afterdepolarizations and triggered activity. AB - One of the possible cellular mechanisms for certain types of ventricular arrhythmias is afterdepolarizations. There are two types of afterdepolarization. The delayed afterdepolarization (DAD) arises from the resting potential after full repolarization of an action potential and it may reach threshold for activation. It is favored by cellular Ca overload, and rapid preceding activation rates. The inward current generating the DAD is caused by one of two mechanisms: a Ca-dependent opening of non-specific cation channels, or Ca activation of a rheogenic Na/Ca exchange. The early afterdepolarization (EAD) arises on the shoulder of a preceding action potential plateau and it is favored by slow preceding activation rate and prolonged action potentials. Ca channels are usually responsible for the inward current for EAD's, and cellular Ca overload is not related. These afterdepolarizations have characteristics that suggest their etiological role in certain arrhythmias found in heart failure. PMID- 1299206 TI - The contribution of nonreentrant mechanisms to malignant ventricular arrhythmias. AB - Evidence obtained from experimental animals and man indicates that reentry is a major mechanism underlying arrhythmogenesis. However, focal or nonreentrant mechanisms also appear to be operative under a wide variety of pathophysiologic conditions. For example, results obtained using three-dimensional (3D) mapping from 232 simultaneous sites in the feline heart in vivo revealed that nonreentrant or focal mechanisms were prominent during both ischemia and reperfusion. During early ischemia, nonreentrant mechanisms were responsible for initiation of ventricular tachycardia (VT) in 25% of cases and, in cases where VT was initiated by reentry, it often could be maintained by a nonreentrant mechanism. During reperfusion of ischemic myocardium, nonreentrant mechanisms were responsible for initiation of VT in 75% of cases. Most importantly, the transition from VT to ventricular fibrillation in response to reperfusion was secondary to acceleration of a nonreentrant mechanism in either the subendocardium or subepicardium. Potential cellular mechanisms include: 1) sarcolemmal accumulation of amphiphiles such as long-chain acylcarnitines and lysophosphatidylcholine; 2) alpha- and beta-adrenergic mediated effects of catecholamines on the transient inward current (ITI) secondary to an increase in intracellular Ca2+; and 3) alpha-adrenergic receptor-induced decrease in IK mediated by activation of protein kinase C. Recent findings obtained using 3D intraoperative mapping in patients with refractory VT and a previous myocardial infarction also indicate that both reentrant and nonreentrant or focal mechanisms contribute. For example, in 13 selected patients, mapping was of a sufficient resolution to define the mechanisms of 10 runs of VT. Intraoperative mapping indicated that five runs of VT were initiated by intramural reentry, whereas five runs of VT were initiated by a focal or nonreentrant mechanism. The mechanisms underlying ventricular arrhythmias associated with ischemic cardiomyopathy have recently been delineated in dogs after multiple sequential intracoronary embolizations with microspheres (with a decrease in mean ejection fraction from 64% to 25%). Spontaneous VT initiated by focal mechanisms from the subendocardium in 82% and epicardium in 18%, with no evidence of macroreentry. Thus, in divergent pathophysiologic settings, nonreentrant mechanisms appear to contribute importantly to the genesis of lethal ventricular arrhythmias, suggesting that development of novel therapeutic approaches should be directed at inhibition of not only reentrant circuits, but also nonreentrant mechanisms, including triggered activity. PMID- 1299207 TI - The potential role of Ca2+ for electrical cell-to-cell uncoupling and conduction block in myocardial tissue. AB - Ca2+ ions are often invoked as potential initiators of cardiac arrhythmias in pathophysiological situations which are associated with an increase of free [Ca2+]i. It is well documented that elevated [Ca2+]i may produce SR release of Ca2+ and oscillations of membrane potential, thereby leading to triggered or spontaneous ectopic activity. The relation among elevated free [Ca2+]i, electrical cell-to-cell coupling, conduction slowing, and reentrant arrhythmias is more speculative. If Ca2+ (e.g. in mechanically injured cells) has direct access to the cellular interconnections (gap junctions), rapid uncoupling occurs at [Ca2+]i which is even within the range of a normal contractile cycle. If cellular integrity is preserved and changes of [Ca2+]i are imposed by extracellular interventions, the effect of [Ca2+]i is critically dependent on pHi. At normal pHi, transcellular conductance remains normal even if [Ca2+]i is increased to bring the cells into a hypercontractile state (> 1-2 microM). At decreased pHi, rapid uncoupling develops at low [Ca2+]i. Comparison of the conduction delay between two cells (or conduction velocity in a simulated conducting medium) with the [Ca2+]i-mediated increase in coupling resistance suggests that the transition from normal conduction velocity to conduction block (a key event in re-entrant arrhythmias) occurs within a relatively narrow range of [Ca2+]i or pHi, almost like a threshold phenomenon. Major efforts have been made in recent years to assess the changes of electrical cell-to-cell coupling and [Ca2+]i in myocardial ischemia. Therefore, the discussion of the role of [Ca2+]i as a modulator of electrical coupling is made in this pathophysiological setting. Comparison of several studies indicate that cell-to-cell resistance and [Ca2+]i in ischemia increase at the same time (10-15 min after perfusional arrest). Since other potential uncoupling processes (delta ATP, delta Mg2+, amphiphilic metabolites, delta pHi) show a similar time-course, it is difficult to attribute cell-to-cell uncoupling in ischemia solely to an increase in [Ca2+]i. Both an initial decrease of membrane excitability and subsequent electrical cell-to-cell uncoupling characterize the early phase of ischemia. The first mechanism is assumed to be more important for the generation of conduction block and re-entry. However, Ca(2+)-induced cell-to-cell uncoupling may partially contribute to the second phase of the early ischemic arrhythmias and mark the transition from reversible to irreversible ischemic damage. PMID- 1299208 TI - Mechanisms of cardiac growth. The role of the renin-angiotensin system. AB - Hypertension is associated with cardiac hypertrophy, which is a structural adaptation of the heart in order to attenuate the systolic stress on the left ventricle. As cardiac myocytes cannot divide, they increase in mass and volume, probably by activating second messengers and proto-oncogenes involved in cellular differentiation and proliferation. Various mechanisms, such as pressure overload and angiotensin II (Ang II), have been proposed to trigger cardiocyte growth and left-ventricular hypertrophy (LVH). In both cases, activation of second messenger routes which increase the intracellular calcium concentration, protooncogene expression, and protein synthesis have been demonstrated. Ang II also facilitates the action of another trophic agent for cardiocytes, which is noradrenaline (NA). In addition, the prevention and reversal of LVH by inhibitors of angiotensin converting enzyme (ACE) suggests a key role for Ang II. However, no conclusive evidence has demonstrated the role of a single pathophysiologic factor in LVH. Therefore, it is more attractive to suggest a link between high blood pressure, renin-angiotensin and other vasoactive systems, such as the adrenergic system, which might together lead in a synergistic way to cardiac hypertrophy. PMID- 1299209 TI - Cardiac fibroblasts: function, regulation of gene expression, and phenotypic modulation. AB - Cardiac fibroblasts constitute the majority of the non-myocyte cell population in the ventricular myocardium. These cells are located in the interstitium, in areas between and surrounding cardiac myocytes. Cardiac fibroblasts are responsible for the synthesis of extracellular matrix proteins such as fibrillar collagen types I and III, basement membrane type IV collagen, fibronectin, and laminin. In addition to its role in muscle development and myoblast differentiations, extracellular matrix consisting primarily of fibrillar collagen is an intricate and highly organized structure that serves to support cardiac myocytes and to maintain functional integrity of the myocardium. Balanced synthesis and degradation of this matrix is the key to normal development of cardiac muscle and perfect myocardial function. Collagen remodeling and accumulation has been demonstrated in several experimental models of cardiac hypertrophy. To gain insights into molecular and cellular mechanisms that affect cardiac fibroblast behavior, cardiac fibroblasts from rat and rabbit ventricular myocardium were cultured and the impact of neurotransmitters and growth factors such as norepinephrine and transforming growth factor--beta (TGF-beta 1), to which cardiac fibroblasts are exposed in vivo, was studied. Results of these studies, with regards to gene expression, proliferation and differentiation of cardiac fibroblasts in culture, and their biological implications are discussed. PMID- 1299210 TI - Signaling mechanisms for the activation of an embryonic gene program during the hypertrophy of cardiac ventricular muscle. AB - To study the signaling mechanisms which mediate ventricular hypertrophy, we utilized the induction of the ANF gene as a marker of the hypertrophic response. The induction of the atrial natriuretic factor gene (ANF) is one of the most conserved features of ventricular hypertrophy, occurring in multiple species (mouse, rat, hamster, canine, and human) in response to diverse stimuli (hormonal, mechanical, pressure/volume overload, genetic, IHSS, hypertension, etc.). The ANF gene is expressed in both the atrial and ventricular compartments during embryonic development, but shortly after birth ANF expression is down regulated to negligible levels in the adult myocardium. Since the reactivation of ANF gene expression in the hypertrophied ventricle is a hallmark of the activation of an embryonic gene program, it has also become of interest to determine if similar mechanisms activate ANF expression during hypertrophy and the initial stages of cardiogenesis. A combination of cotransfection, microinjection, and transgenic approaches has been coupled to well characterized cultured cell systems and in vivo murine models employing normal and transgenic mice. The microinjection of oncogenic RAS proteins into living myocardial cells does not lead to the activation of cell proliferation, but activates ANF gene expression, as assessed by immunofluorescence. Co-transfection of mutant and wild type RAS expression vectors with a ANF-luciferase fusion gene supports a direct effect of activated RAS on ANF gene transcription. Co-transfection of a dominant negative RAS vector effectively inhibits the induction of the ANF gene during alpha adrenergic mediated hypertrophy of ventricular muscle cells, thereby establishing that a RAS-mediated pathway is required for ANF induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299211 TI - Endothelial modulation of myocardial contraction: mechanisms and potential relevance in cardiac disease. AB - Recent studies in isolated cardiac preparations and the intact heart demonstrate that the endocardial and coronary vascular endothelium modulate myocardial contractile behaviour and cardiac pump function in a novel manner, mainly by influencing the duration of contraction and the onset of relaxation but without major effect on early systolic contractile characteristics. These effects are mediated by the release of at least two diffusible substances from endothelial cells: a) endothelium-derived relaxing factor (EDRF) which shortens contractile duration by elevating myocardial cyclic GMP, and b) a novel substance, provisionally named "endocardin", which prolongs contractile duration. Under physiological conditions these endothelial influences may be particularly important for relaxation and early diastolic filling events in the heart. It is possible that they could influence myocardial growth, interact with other cardiac hormones, and via EDRF inhibit platelet adhesion to endothelial surfaces. The release of the endothelial factors is regulated by stimuli such as circulating neurohumoral substances, increased flow, products of platelet aggregation, and endogenous peptides stored in endothelial cells. Although experimental evidence is still limited, it seems likely that cardiac endothelium may play an important role in the pathophysiology of cardiac disease, e.g. overload-induced hypertrophy. The endothelium could a) influence the development of phenotype change by modulating and mediating transduction of extrinsic signals, b) contribute to contractile and other abnormalities (especially "diastolic" dysfunction) because of loss or impairment of its normal function, and c) be uniquely amenable to therapeutically useful pharmacological manipulation. PMID- 1299212 TI - Energetics of calcium cycling in nonfailing and failing human myocardium. AB - Using sensitive antimony-bismuth thermopiles, isometric force and heat output were measured in muscle strips from nonfailing human hearts and from failing dilated cardiomyopathic hearts at a stimulation rate of 60 beats per minute (37 degrees C). This frequency was chosen because analysis of the force-frequency relation showed significant differences in isometric force between failing and nonfailing human myocardium at 60 beats per minute and at higher frequencies, whereas at lower rates of stimulation (30 beats per minute) force of contraction was similar in failing and nonfailing myocardium. The liberated initial heat was partitioned into its two components, tension-dependent heat and tension independent heat from high-energy phosphate hydrolysis by contractile proteins and excitation-contraction coupling processes, respectively. Tension-dependent heat reflects the total number of crossbridge interactions, and tension independent heat is an index of the amount of calcium cycling during the contraction-relaxation cycle. In failing compared to nonfailing human myocardium, peak twitch tension, maximum rate of tension rise and maximum rate of tension fall were reduced significantly. Reduced mechanical performance was associated with reduced liberation of both tension-dependent and tension-independent heat in the failing heart. The reduction of tension-dependent heat by 61% and of tension independent heat by 69% indicate considerable decreases in the number of crossbridge interactions activated and calcium ions cycled during the isometric twitch. In addition, the rate of calcium removal was reduced in the failing human heart as is indicated by a 71% reduction in tension-independent heat rate. The efficiency of excitation-contraction coupling with respect to crossbridge activation was similar in failing and nonfailing myocardium. These data indicate that impaired myocardial performance in dilated cardiomyopathy may result from disturbed excitation-contraction coupling with reduced amount of calcium cycling and reduced rate of calcium removal. PMID- 1299213 TI - Spontaneous sarcoplasmic reticulum Ca2+ release leads to heterogeneity of contractile and electrical properties of the heart. AB - The cytosolic Ca2+ (Cai) oscillation generated by the sarcoplasmic reticulum (SR) in response to an action potential (AP) occurs relatively synchronously within and among cells. The SR can also generate spontaneous Cai oscillations (S-CaOs), i.e., not triggered by sarcolemmal depolarization. The local increase in Cai due to S-CaOs is equivalent to that induced by an AP. Heterogeneity of diastolic Cai caused by asynchronous S-CaOs among cells within myocardial tissue leads to heterogeneous myofilament activation, the summation of which produces a Ca(2+) dependent component to diastolic tone. The local increases in Cai due to S-CaOs also cause oscillatory sarcolemmal depolarizations due to Ca2+ modulation of the Na/Ca exchanger and of non-specific cation channels. Thus, inhomogeneous levels of diastolic Cai may lead to heterogeneity in cell coupling and thus may also affect the impulse conduction. The magnitude of the S-CaOs induced diastolic tonus and membrane depolarization varies with the extent to which S-CaOs are synchronized; partially synchronized S-CaOs following an AP induced SR Ca2+ release produce an aftercontraction and after depolarization. When local S-CaOs is sufficiently synchronized within the cell the resultant depolarization summates and can be sufficient to trigger spontaneous AP. Inhomogeneity of diastolic SR Ca2+ loading and sarcomere lengths within individual cardiac cells due to S-CaOs leads to inhomogeneous systolic Cai levels and sarcomere length inhomogeneities in response a subsequent AP; this heterogeneity compromises the systolic contraction amplitude. Heterogeneity of systolic Cai among cells due to diastolic S-CaOs also leads to heterogeneity of AP repolarization times, due, to heterogeneous Cai modulation of the Na/Ca exchanger, the non-specific cation channel and of the L type sarcolemmal Ca2+ channel. S-CaOs occurrence during a long AP plateau may also modulate the removal of voltage inactivation of L type Ca2+ channels and affect the likelihood of the occurrence of "early after depolarizations." Thus, as a single entity, S-CaOs may be implicated in diverse manifestations of heart failure--impaired systolic performance, increased diastolic tonus and an increased probability for the occurrence of arrhythmias. PMID- 1299214 TI - [Isolation, structure and properties of new endogenous peptides]. AB - Large scale isolation and determination of amino acid sequences of endogenous peptides from various biological sources (bovine brain and red bone marrow, siberian ground squirrel brain) were carried out. A number of earlier unknown peptides were identified, many of them showing distinct activity in vivo and/or in vitro. Analysis of more than 170 isolated peptide structures resulted in the hypothesis suggesting functional proteins, in particular hemoglobin, to serve also as a source of the peptide "background" which has its own biological significance. Further directions of investigating the endogenous peptide material are mapped. Its potential for developing diagnostics for somatic diseases is demonstrated on patients with CNS disorders. PMID- 1299215 TI - Mapping the functional topography of a receptor. AB - Photoactivatable derivatives of the alpha-neurotoxin II from Naja naja oxiana are useful tools for investigating the three dimensional architecture of the extra membrane part of the nicotinic acetylcholine receptor from the electric tissue of Torpedo californica. Three derivatives, carrying an azidobenzoyl group in position Lys-15, Lys-26, and Lys-46, respectively, are shown to react differently within the receptor's quaternary structure. Especially the Lys-26 and Lys-46 derivatives can be used for differentiating between the two nonequivalent alpha subunits. The Lys-26 derivative is applied for probing the receptor subunits next to the alpha-subunit: the gamma-subunit is shown to be located next to the alpha subunit binding d-tubocurarine with high affinity. The delta-subunit is the neighbor of the low affinity alpha-subunit. We radioiodinated the toxin derivatives and localized the 125I at the His-31 residue of the toxin. Very little label was found in position Tyr-24, the only tyrosine residue of the toxin, or in position His-4, the only other histidine residue. This result is important for the cleavage experiments necessary in attempts to identify the receptor sequence which reacted with the photolabel. PMID- 1299216 TI - [Cell membranes as a barrier during biological uses of antisense oligonucleotides, their derivatives, and analogs]. AB - Use of oligonucleotides and their derivatives as gene targeted drugs encounter a problem of crossing of lipophilic cell membranes by these hydrophilic compounds. This paper considers the approaches to overcome the arising barrier: 1) penetration by endocytosis in the presence of bivalent cations; 2) use of non ionic oligonucleotide analogs; 3) attachment of bulky hydrophobic radicals; 4) use of membrane carriers; 5) interaction of oligonucleotides and their derivatives with specific receptors. PMID- 1299217 TI - [New strategies for DNA sequencing and determining protein location in genomic DNA]. AB - A new technique of DNA sequencing by hybridization with oligonucleotide matrix (SHOM) has been tested in model experiments. The paper also describes a number of new approaches to protein identification and their mapping on any particular region of genomic DNA. PMID- 1299218 TI - [Gene expression in cell-free systems on a preparative scale]. AB - In vivo expression of foreign or synthetic genes can be subject to certain restrictions such as protein aggregation, degradation and toxicity. Conventional in vitro systems can overcome these problems, but in turn suffer from other limitations, in particular short life-time and low protein yield. In this review, two types of gene expression system are described. Both are based on the novel concept of the enhanced expression from cell-free extracts where incubation is performed in the continuous flow of a feeding solution rather than in a fixed volume of a test-tube. The first type makes use of cell-free translation of mRNA templates in either prokaryotic or eukaryotic cell lysates. The second utilizes the coupled transcription--translation of DNA templates, with genes transcribed by either endogenous or bacteriophage RNA polymerases. In both systems, translation can be carried out over tens or hundreds of hours resulting in high protein yields. PMID- 1299220 TI - N.m.r. study on the formation and geometry of inclusion complexes of 6-O-(alpha maltosyl)cyclomalto-hexaose and -heptaose with p-nitrophenol in aqueous solution. AB - The formation and molecular geometry of inclusion complexes of some branched cyclomaltaoses with p-nitrophenol in aqueous solution have been investigated by using high-resolution 1H-n.m.r. spectroscopy. 6-O-(alpha-Maltosyl)cyclomalto hexaose and -heptaose were found to form 1:1 inclusion complexes with p nitrophenol, and the dissociation constants for their complexes are quite similar to those for corresponding unbranched cyclomaltaose-p-nitrophenol complexes, indicating that formation of these inclusion complexes is not hampered by the maltosyl branch. From measurement of nuclear Overhauser enhancements, it was concluded that the maltosyl branch is not situated over the entrance of the cavity. PMID- 1299219 TI - [Some results and prospects of studies in the area of marine biochemistry and biotechnology]. AB - Recent studies on bioactive metabolites from marine macro- and microorganisms are reviewed with 83 refs. Structures of new sulphated and glycosylated secondary metabolites, which have been reported to have antifungal, immunomodulatory, and cytotoxic properties, are given. Some peculiarities of biosynthesis of natural compounds in marine organisms are revealed. It was shown that some natural products, isolated earlier from sponges, are produced by microbial symbionts. Different physiological activities associated with 8000 marine microbial (mainly symbiotic) strains are discussed as well as some prospects of marine biochemistry and biotechnology development. PMID- 1299221 TI - Ab initio studies of aromatic-aromatic and aromatic-polar interactions in the binding of substrate and inhibitor to dihydrofolate reductase. AB - Aromatic-aromatic and aromatic-polar interactions are investigated by performing ab initio Hartree-Fock calculations. Binding energies and optimum distances between subsystems are obtained. It is found that the binding energy between two benzene rings is of 3.1 kcal/mol when correlation effects are included, while the serine aromatic complexes energies of binding range from 1.9 to 3.1 kcal/mol. PMID- 1299223 TI - [Variations in hospitalization rates of non-neonatal hospital admissions to pediatric departments of three district hospitals]. AB - Hospitalization rates of children from three health districts were analyzed. The rates ranged from 30 to 40 admissions per 1000 children. The length of hospital stay, the rates of transfers and deaths were similar. Admission rates were different for certain selected diagnoses: gastroenteritis, pneumonia, bronchiolitis, head trauma and ear, nose and throat procedures. The variations were not related to differences in physician or bed supply, nor to severity or the disease of a delay in getting medical care. The demographic and geographic characteristics and the different patterns of practice can be associated with the observed variations. The health status of these children must be determined before considering which rate is correct. PMID- 1299222 TI - Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation. AB - Major histocompatibility complex (MHC) class I molecules bind and deliver peptides derived from endogenously synthesized proteins to the cell surface for survey by cytotoxic T lymphocytes. It is believed that endogenous antigens are generally degraded in the cytosol, the resulting peptides being translocated into the endoplasmic reticulum where they bind to MHC class I molecules. Transporters containing an ATP-binding cassette encoded by the MHC class II region seem to be responsible for this transport. Genes coding for two subunits of the '20S' proteasome (a multicatalytic proteinase) have been found in the vicinity of the two transporter genes in the MHC class II region, indicating that the proteasome could be the unknown proteolytic entity in the cytosol involved in the generation of MHC class I-binding peptides. By introducing rat genes encoding the MHC-linked transporters into a human cell line lacking both transporter and proteasome subunit genes, we show here that the MHC-encoded proteasome subunit are not essential for stable MHC class I surface expression, or for processing and presentation of antigenic peptides from influenza virus and an intracellular protein. PMID- 1299224 TI - Ablation of transplanted HTLV-I Tax-transformed tumors in mice by antisense inhibition of NF-kappa B. AB - Mice transgenic for the human T cell leukemia virus (HTLV-I) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes. In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line. In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth. Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas. This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease. PMID- 1299225 TI - Nutritional management of osteoporosis. To slow the advancement of osteoporosis, nurses must encourage their clients to increase their intake of calcium. For geriatric nurses, this may be a challenge. AB - In conclusion, no current effective therapy is available for the restoration of bone mass once osteoporosis has developed. Primary prevention is the best way to fight this problem. However, goals for the management of osteoporosis are (1) to maintain skeletal mass and integrity, (2) to slow bone resorption, and (3) to treat the symptomatic problem and its sequelae. Having a well-balanced diet containing adequate amounts of calcium, use of calcium supplements when necessary, reducing risk factors in life-style, and use of estrogen are therapeutic measures to reduce bone loss. Clients are also encouraged to exercise by walking or swimming and remain as active as possible. It is important to avoid strain on the spine, as occurs in lifting or bending, to prevent compression fractures on the vertebrae. For treating the symptoms of osteoporosis and its sequelae, it is necessary to relieve pain (by the use of analgesics), provide comfortable light mechanical support for the spine, if needed, arrange assistance in activities of daily living, coordinate a rehabilitation program, and provide emotional support and reassurance to the patient and family. This may be an area largely neglected in practice. Gerontologic nurses may be the first to take the time to thoroughly discuss osteoporosis with their elderly clients and help them to develop a comprehensive program. If through their efforts some falls and fractures can be prevented, this is nursing at its best. PMID- 1299226 TI - Cirrhotic changes in livers from children undergoing transplantation. Image analysis. AB - The pattern and extent of disorganization of the liver architecture were studied in 25 children undergoing orthotopic liver transplantation for cirrhosis. Image analysis techniques based on mathematical morphology were used to define seven parameters for each case, including fibrosis index (percentage of Sirius-red stained areas), three categories of regenerative nodules (< 0.8, 0.8-1.6 and > 1.6 mm in diameter) and three categories of fibrous septa (< 0.4, 0.4-1.2 and > 1.2 mm in width). Fibrosis index ranged from 10.2% to 51.9%. Percentage of small nodules of infralobular size (< 0.8 mm in diameter) varied from 31.4% to 98.2%. Percentage of large nodules, > 1.6 mm in diameter, in only four cases was > 15%. Multivariate clustering analysis classified the cases into three main groups. One of them included only cases of cirrhosis secondary to parenchymal disease or to inborn errors of metabolism. In their pattern, tiny nodules predominated, and the percentage of slender septa, < 0.4 mm in diameter, was very high, although the overall fibrosis index was relatively low. Patients with biliary cirrhosis were classified into two groups. In one the fibrosis index was low and the size of the nodules variable, with 12% large nodules. In the other the fibrosis index was high, and small nodules, < 0.8 mm in diameter, predominated. No relationship was found with age at transplantation or previous portoenterostomy. A presumptive explanation for this divergent evolution might be the occurrence of cholangitic episodes. Overall fibrosis that the liver can sustain without failure is apparently limited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299227 TI - Colorectal carcinoma. DNA ploidy pattern and prognosis with reference to tumor DNA heterogeneity. AB - Nuclear DNA content was measured in 72 colorectal carcinomas using single-cell microspectrophotometry on Feulgen-stained smears. Four samples were analyzed from each tumor. Patients were followed for 41-65 months (average, 53). DNA heterogeneity (both aneuploid and nonaneuploid patterns) was present in 44% of the cases. Sixty-eight percent of the tumors showed an aneuploid DNA pattern in at least one of the samples. Patients with nonaneuploid tumors tended to have a survival advantage over patients with homogeneously aneuploid tumors and demonstrated a significantly longer disease-free survival. The DNA ploidy pattern is of potential value in conjunction with histopathologic prognostic parameters in colorectal carcinoma. Since colorectal tumors exhibit pronounced DNA heterogeneity, multiple samples are required from each tumor to permit a proper evaluation of its DNA pattern. The DNA heterogeneity may represent tumor progression and can partly explain the conflicting results reported concerning DNA pattern and prognosis in colorectal carcinoma. PMID- 1299228 TI - Application of morphometric methods to the cytologic study of intradermal nevi. AB - Twenty-one intradermal nevi were studied by morphometric methods in an attempt to morphologically characterize the two types of nevus cell--epithelioids, type A, and fusiforms, type C--and to quantify the differences between them. Morphometric parameters of the intradermal nevi were compared with similar parameters of melanocytes and melanoma cells so that the maturation rates of the nevi cells could be established and to see if the parameters might indicate the degree of malignancy. Superficial nevus cells were differentiated from deep cells by their larger size and larger nuclear area. Nuclear area appeared to have potential for differentiating benign from malignant tumors. Decrease in cellular area appeared to indicate maturation rather than atrophy. Melanoma cells were differentiated by their larger size. Cell nuclear perimeter appeared to have confirmatory value, while cell perimeter was inconclusive. PMID- 1299230 TI - Implementing a regulation-complaint quality improvement program on a commercial laboratory information system. AB - Implementing a quality improvement (QI) program on an automated laboratory information system (LIS) in the current regulatory climate requires first that the QI program be defined and second that the selected LIS be able to capture important events and use flexible vendor-provided or user-defined routines to prepare reports. Reports key on specific monitors and thresholds defined in the QI program. The product of a pathology laboratory is communicated information. The QI program focuses on the accuracy, clarity and timeliness with which the whole information-generating process functions. To support peer review the LIS must be able to select reports for evaluation based on user-defined parameters, such as diagnosis keyed through Systematized Nomenclature of Medicine codes, or by random or pattern selection by accession number. Counting and review of revised reports will focus attention on accuracy and skill in communication since these indicators often reflect client satisfaction with the report. To link services--e.g., cytology with surgical pathology--the LIS must be able to gather cases from the accession lists of both services and to flag diagnostic inconsistencies. LIS transaction logging at every step in the information process allows tracking of work load, productivity and resource utilization by functional areas and by individual, thus meeting regulatory requirements. Transaction logging also provides management information, such as segmented turnaround time audits, pinpointing sources of delay by kind and location of work or individual involved. Critical data must be held on-line for at least five years. PMID- 1299229 TI - Elliptic Fourier analysis of megakaryocyte nuclei in chronic myeloproliferative disorders. AB - Elliptic Fourier analysis was applied to megakaryocyte nuclei in bone marrow biopsies from 15 patients with chronic myelocytic leukemia with megakaryocyte predominance and from 15 patients with chronic megakaryocytic granulocytic myelosis. To assess the reliability of this procedure, the biopsies were evaluated also by the semiautomatic measurement of nuclear area and form factor, and both methods were compared with respect to the degree of morphologic differences obtained between these two types of chronic myeloproliferative disorders (CMPDs). Discriminant analysis revealed correct reclassification of all cases both for elliptic Fourier analysis and for semiautomatic planimetry, whereas discriminant scores were much higher for Fourier analysis. Thus, simple planimetric features such as nuclear area and form factor, in contrast to Fourier analysis, are not able to detect the full degree of morphologic differences between megakaryocyte nuclei in different CMPDs. Elliptic Fourier analysis therefore seems to be a useful procedure for the accurate description of such complicated structures as megakaryocyte nuclei in CMPD. PMID- 1299231 TI - Surgical treatment of periampullary cancer--review of 766 surgical experiences of 8 hospitals. AB - The incidence of periampullary cancer has been steadily rising in Korea. In the present study, we have reviewed 766 cases of surgically treated periampullary cancers, including 122 cases of our own, which were published in the Korean literature from 1984 to 1992. The 6th decade was the most prevalent age group, occupying 38% of the patients. The ratio of male of female was 1.7 to 1. Approximately 60% of lesion located at the head of the pancreas. Computed tomography which had 85% sensitivity was the most commonly employed modality for a diagnosis. The diagnostic sensitivity of percutaneous transhepatic cholangiography was 72%, of endoscopic retrograde cholangiopancreatography was 71%, and of ultrasonography was 54% in order of frequency. Tumor markers such as CA-19, CEA, and CA-125 were also studied in pancreatic cancer. The combinations of these markers recorded a higher positivity than using solely. The resection rate for lesions at the head of the pancreas was 21%, and that of distal common bile duct, ampulla of vater, and duodenum were 37%, 85%, and 50%, respectively. The morbidity and mortality rates after pancreatoduodenectomy were 44% and 12%, respectively. TNM staging revealed 66% of patients were in stage III, 26% in stage I, and 8% in stage II. The actual 5-year survival rates for cancer of the head of the pancreas was 11%, and that of duodenal cancer, distal choledochal cancer, and ampullary cancer were 21%, 18%, and 15%, respectively. In nonresected group, none survived over 18 months after treatment. Relatively high portion of lymph node metastatic patients may explain the poor survival observed in our series. PMID- 1299232 TI - Internal capsular lesion associated with dizziness. AB - It has been known that the vestibular system is concerned with feelings of dizziness or vertigo. The vestibulo-thalamic pathway has also been described previously. However, there has been no confirmative report so far regarding the pathway through the internal capsule to the cortex. We have experienced 13 patients with symptoms of dizziness and/or vertigo whose lesions are located only around the internal capsule, mainly at the posterior limb and/or the genu. It is suggestive that fibers with dizziness may pass through a part of the internal capsule, probably through some part of the posterior limb and/or the genu. PMID- 1299233 TI - Polymorphonuclear leukocyte functions enhanced by chemotaxis. AB - Human polymorphonuclear leukocytes (PMN) migrate into tissues in response to chemoattractants, yet it is not known whether this process alters the functional capabilities of the PMN. Using recombinant human interleukin-8 (rHIL-8, 100 ng/ml) as a stimulus, we compared a population of PMN that migrated through a polyvinylpyrrolidone-coated polycarbonate filter containing 8.0 microns diameter pores with PMN stimulated in suspension. PMN were analyzed by flow cytometry according to functional and phenotypic criteria. CD11b/CD16 expression was unaltered by chemotaxis. In contrast, chemotaxis enhanced phagocytosis of E. coli, independent of opsonization with IgG. Similarly, chemotaxis increased baseline hydrogen peroxide production. We conclude that the chemotactic motion of PMN "primes" the cell for increased oxidative burst activity and augments the ability of PMN to ingest bacteria. This increased functional capability is distinct from rHIL-8 stimulation and appears to be independent of complement-and Fc-receptor expression. PMID- 1299234 TI - Malignant lymphomas of the nasal cavity and Waldeyer's ring--clinicopathologic and immunohistochemical study. AB - The clinicopathologic and immunohistochemical finding of 10 cases of nasal non Hodgkin's lymphoma (NHL) and 23 cases of Waldeyer's ring NHL were studied. Immunohistochemically, nasal NHL expressed T-cell markers exclusively, whereas the NHL of Waldeyer's ring were of both T-cell (56.5%) and B-cell lineages (43.5%). Angioinvasiveness by tumor cells was exclusively noted in the T-lineage lymphomas. Epithelial hyperplasia, epitheliotropism by tumor cells, and extensive invasion of adjacent normal tissue were more prominent in T-cell lymphomas than in B-cell lymphomas. T-lineage lymphomas showed distant extranodal spread pattern involving the skin, soft tissue, stomach, spleen, and the liver, whereas B lineage lymphomas tended to localize in the lymph nodes. The survival rate of Nasal NHL was similar to that of Waldeyer's ring NHL. Although not statistically significant because of small sample numbers, immunophenotype, histologic groups of monomorphic lymphoma, and stage had prognostic importance. In general, T lineage lymphomas presented with a higher stage than B-lineage lymphomas (p < 0.05)-and overall survival was poor. Stage I disease showed a much more favorable prognosis than stage II disease. Monomorphic lymphomas had a shorter survival than polymorphic reticulosis (PR) or lymphomas with features of PR. This result in conjunction with the morphologic transition between them suggested that monomorphic lymphoma may represent the most advanced stage in the spectrum of PR, lymphoma with features of PR, and monomorphic lymphoma. PMID- 1299235 TI - Percutaneous transhepatic biliary biopsy using gastrofiberscopic biopsy forceps. AB - To obtain a histopathologic diagnosis at the site of a biliary obstruction, we recently have performed 24 cases of biliary biopsy using gastrofiberscopic biopsy forceps (Olympus, Tokyo, Japan) via transhepatic tracts provided in the course of the procedure of percutaneous biliary drainage. Histopathologic diagnosis was successfully made at the first attempt of biopsy procedure but a second trial was made a week later in 6 cases who were negative for malignant cells on the first attempt. The histological results from the biopsy specimens were 18 adenocarcinomas, 5 chronic inflammations and one normal epithelium. Of 6 cases who were negative for malignant cells on forceps biopsy specimen, three cases were confirmed as adenocarcinoma of the ampulla of Vater, adenocarcinoma of the pancreas and chronic pancreatitis by surgical biopsy. The latter was a true negative result, which was diagnosed as chronic inflammation on forceps biopsy and verified as chronic pancreatitis by surgery. The remaining two cases were diagnosed as malignant obstructive jaundice by clinical and radiological follow up findings. Major complications (bile peritonitis, bleeding, and hemopneumothorax) occurred in 3 patients, which mainly arose in the earlier period of study. This procedure can be performed at the same time as percutaneous transhepatic biliary drainage with low morbidity or mortality, and although the potential for perforation of bile ducts and injury to adjacent blood vessels is considered it is a useful addition to existing biopsy techniques for yielding material sufficient for histologic analysis. PMID- 1299236 TI - Heterologous corneal endothelial cell transplantation--human corneal endothelial cell transplantation in Lewis rats. AB - A heterologous corneal endothelial transplantation was attempted using human endothelial cells and a Lewis rat penetrating keratoplasty model. Cultured human endothelial cells were seeded to a Lewis rat cornea, which was denuded of its endothelium. When grafted into the syngeneic Lewis rat, the graft remained clear for at least five days, and then became opaque and edematous because of immune rejection reaction. In contrast, corneas denuded of their endothelium became opaque and edematous immediately after transplantation. These results demonstrate that transplanted endothelial cells have enough antigens to induce rejection reaction even though they have the functional capacity to deturge the cornea. PMID- 1299237 TI - Studies on the role of interleukin-4 and Fc epsilon RII in the pathogenesis of minimal change nephrotic syndrome. AB - Childhood minimal change nephrotic syndrome (MCNS) has often been associated with allergic symptoms such as urticaria, bronchial asthma, atopic dermatitis, allergic rhinitis and elevated IgE levels and referred to involve immune dysfunction. Fc epsilon RII is known to be involved in IgE production and response. Interleukin-4 is being recognized as a major cytokine up-regulating IgE production. Hence the present study is aimed at investigating the role of interleukin-4 and Fc epsilon RII in the pathogenesis of MCNS. IgE was measured by ELISA. Fc epsilon RII was analyzed by fluorescence activated cell scanner (FAC scan) by double antibody staining with anti Leu16-FITC and anti Leu20-PE. Soluble IgE receptor was measured by ELISA using anti CD23 antibody (3-5-14). Interleukin 4 activities were measured by CD23 expression on purified human tonsillar B cells. Serum IgE levels were significantly higher in MCNS (1,507 +/- 680 IU/dl) than in normal controls (123 +/- 99.2 IU/dl). A significantly higher expression of membrane Fc epsilon RII was noted for MCNS (41 +/- 12%) than that in normal controls (18 +/- 6.2%) (p < 0.001). Soluble CD23 levels were also significantly higher in MCNS (198 +/- 39.3%) than in normal controls (153 +/- 13.4) (p < 0.01). Interleukin-4 activity in sera of MCNS (12U/ml) was also significantly higher than normal controls (4.5U/ml). These results indicate that increased production of Fc epsilon RII and interleukin-4 may play an important role in the pathogenesis of MCNS. PMID- 1299238 TI - Papillary muscle necrosis in neonates and infants--analysis of 209 autopsies. AB - A total of 209 consecutive neonate and infant autopsies were reviewed with special attention to papillary muscle necrosis (PMN) of the heart. Associated major pathological findings were analysed for the evaluation of significant pathological accompaniments of PMN. PMN was found in 52 cases among 171(30.4%) neonates and major pathological accompaniments were bronchopneumonia, hyaline membrane disease, hypoxic neuronal change, sepsis, subarachnoid hemorrhage, disseminated intravascular coagulation (DIC) and acute tubular necrosis, among which hypoxic neuronal change and ATN had a statistically significant higher incidence when compared with the control group. (p < 0.005). PMN was found in 13 cases among 38(34.2%) infants and accompaniments were congenital heart disease, sepsis, bronchopneumonia, DIC and hypoxic neuronal change, all of which showed no difference from the control group in incidence. The results imply that PMN is a kind of organ damage in stressed subjects regardless of age, that it is not a special form of myocardial injury in any specific age group including the newborn period, and is possibly of different pathogenesis and significance. PMID- 1299239 TI - Acetylcholinesterase histochemistry of rectal suction biopsies in the diagnosis of Hirschsprung's disease. AB - Rectal suction biopsy with acetylcholinesterase (AChE) histochemistry has gained increased acceptance as the means of definitely diagnosing Hirschsprung's disease (HD) as well as of excluding this diagnosis when evaluating children with low intestinal obstruction or chronic constipation since the report of Meier-Ruge et al. in 1972. But this AChE histochemical study has not been reported yet in Korea. During the 14-month period from April, 1991 through June, 1992, 37 children, aged 3 days to 17 years had rectal suction biopsies for the diagnosis or exclusion of HD. In this study, AChE histochemistry (N = 37) was compared with hematoxylin & eosin (H&E) staining of same suction biopsy specimens (N = 35) for diagnostic accuracy. The histochemical criterion used for the diagnosis of Hirschsprung's disease was that of Chow et al. (1977), i.e., the presence of many coarse discrete cholinergic fibers in the muscularis mucosae and in the immediately subjacent submucosa regardless of an infiltration of cholinergic fibers in the lamina propria. Of 13 biopsies from the patients with Hirschsprung's disease (N = 13), there were 12 positive reactions, and one false negative reaction in a neonate with total colonic aganglionosis. All biopsies from 24 unaffected children demonstrated negative reactions with no false positive reaction. In comparison, of the 35 specimens examined by H&E staining, ganglion cells were present in the submucosal Meissner's plexus only in 15 of these 24 unaffected children. In conclusion, a 97% diagnostic accuracy was achieved with AChE histochemistry compared with a 74% accuracy with H&E staining (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299240 TI - Differential pattern of perivascular type IV collagen deposits in phyllodes tumors of the breast. AB - Deposition of basement membrane extracellular matrix is influenced by adjacent tumor cells, and in some cases, the pattern of type IV collagen deposit is characteristic in malignant tumors. In this report, we analyzed the difference in type IV collagen deposition patterns between benign and malignant phyllodes tumors (PTs) of the breast. Of the 15 cases of PTs, 8 cases were benign PTs and 7 cases were malignant PTs. Three cases of other primary sarcomas of the breast (stromal sarcoma, angiosarcoma and osteosarcoma) and 2 cases of fibroadenomas were studied for comparison. The malignant PTs were distinguished from benign ones by increased mitotic figures, cellular atypism, and a higher proliferation index of stromal cells. Immunohistochemical staining against type IV collagen in malignant PTs revealed extensive to moderate deposition of type IV collagen around the small blood vessels in duplicate or multilayering pattern, while benign PTs showed minimal deposition in a single linear pattern. All of the three cases of other sarcomas revealed multilayering or meshwork pattern of type IV collagen around the blood vessels. The deposition of type IV collagen around the blood vessels may reflect the malignant behavior of the stromal tumors of the breast. PMID- 1299241 TI - Spinal meningeal melanocytoma. AB - A case of spinal meningeal melanocytoma is reported along with clinicopathologic, immunohistochemical and ultrastructural studies. This patient presented clinically with paraparesis, tingling sensation and numbness of both lower extremities of 4 months duration. No mucocutaneous pigmented nevi were found. On operation, scattered coal-black pigmented lesions were found in the meninges between T3 and T4-5 interspace level. Nearly total removal was carried out. The tumor was composed of spindle and epithelioid cells with heavy brown-black pigmentation. There was no pleomorphism, mitosis, hemorrhage, necrosis or invasion to the underlying cord tissue. In Korea, this case appears to be the first example of this disease. Neurologic deficit improved after surgical excision. PMID- 1299242 TI - Primary choriocarcinoma of the urinary bladder--a case report. AB - We report a primary choriocarcinoma of the urinary bladder in a 63-year-old man who presented with painless hematuria. He was diagnosed as having an invasive carcinoma and underwent a total cystectomy. The tumor was diffusely hemorrhagic and occupied the dome of the bladder. Histologically, it consisted of cyto-and syncytiotrophoblasts with extensive hemorrhage. No coexisting transitional cell carcinoma component was present. By immunohistochemistry, the tumor expressed beta-hCG and low-molecular weight cytokeratin intensely while it was negative for CEA or EMA. The post-cystectomy serum beta-hCG was 237mlU/ml, and decreased later. The pertinent literature is reviewed and diagnostic criteria are discussed. PMID- 1299243 TI - An unusual combination of trisomy 21 and partial trisomy 5q. AB - The authors describe a male newborn with multiple congenital anomalies; craniofacial dysmorphism, bilateral cleft palate and lip, ambiguous external genitalia with absence of phallus, ventricular septal defect, agenesis of olfactory bulbs, and presence of small round cells simulating migration defect in the cerebellar white matter. Cytogenetic study demonstrated a chromosomal constitution of 47,XY, +21, +5q. Its pathological significance compared with Down's syndrome and hitherto reported partial trisomy 5q is discussed. PMID- 1299245 TI - A family case of beta-thalassemia minor and hemoglobin Queens: alpha 34 (B15) Leu Arg. AB - We report a Korean family case of beta-thalassemia minor and Hb Queens. This is the first case report of Hb Queens in Korea. A 43-year-old male and his four family members had beta-thalassemia minor which is very rare in Korea. Incidentally, an alpha chain variant with a high isoelectric point was also found in two other family members without clinical problems and was finally identified as alpha 34 (B15) Leu-Arg or Hemoglobin Queens. PMID- 1299244 TI - Acute leukemias with unusual immunophenotypes. AB - Over a two-year period, immunophenotypic patterns of 266 acute leukemia cases were analyzed using a panel of tests including TdT, SmIg and 9 surface antigens by the immunofluorescence stains for the assessment of the incidence and grade of phenotypic ambiguity (lineage infidelity) and the possible clinical significance of unusual immunophenotypes. Immunophenotypes were classified into four groups according to the degree of ectopic antigen expression. We classified as Group A (91.7%, 244 of 266 cases) those expressing conventional pattern without ectopic antigen. Group B (3.0%, 8 of 266 cases) was defined to have at least two lineage specific markers and single ectopic antigen. Such a "low grade deviation" did not prevent a definite immunodiagnosis. Group C (4.2%, 11 of 266 cases) revealed a promiscuous coexpression of markers related to different lineages, including two cases (0.8%, 2 cases) of biphenotypic leukemia. Group D (1.1%, 3 cases) included unclassifiable immunophenotypes with no antigen or HLA-DR only expression. Both patients with biphenotypic leukemia and one patient with unclassifiable immunophenotypes failed to respond to induction chemotherapy, suggesting a poor prognosis in these patients. The incidence of acute myelogenous leukemia (AML) cases with one or more ectopic surface antigens was 10 (8.1%) of the 124 AML cases. Ectopic antigen expression was seen in 5 (4%) of the 125 B-lineage acute lymphoblastic leukemia (ALL) cases and 3 (25%) of the 12 T-ALL cases. It is concluded that nearly 95% of cases of acute leukemia cases can be diagnosed accurately with immunophenotyping alone including patients with a mild degree of deviation from expected antigenic patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299246 TI - Effect of etching time and acid concentration on resin shear bond strength to primary tooth enamel. AB - The present study compared the shear bond strength of two commercially available systems to human primary enamel. Ground and unground enamel was conditioned for 15 seconds with 37% phosphoric acid siliceous gel. A 60-second application was used as a standard reference. Ten percent phosphoric acid in a polymer gel was also evaluated following a 20-second application to ground and unground primary enamel. No statistically significant difference was demonstrated between the mean values determined for each group. Compared with tests on permanent enamel with the same materials and conditions, it was concluded that no statistically significant difference exists between shear bond strengths to the enamel of the two dentitions. PMID- 1299247 TI - Dentin adhesives and microleakage in cervical resin composites. AB - This paper reports the effect of dentin bonding agents on marginal leakage in cervical cavities without the classical cavity preparation design. Wedge-shaped cervical cavities were cut on extracted teeth with the gingival cavosurface margin of each cavity involving dentin. The specimens were randomly assigned to three groups of 40 each: Group 1 (control), restored with Fuji glass ionomer; Group 2, restored with Scotchbond 2 adhesive and Silux Plus resin and Group 3, restored with Tenure adhesive and Perfection resin. Half of the specimens in each group were thermocycled. All specimens were then stored in basic fuchsin dye after which microleakage of the restorations was assessed by dye penetration. A grading scale of 0 to 3 was used as the scoring criteria. The results showed that differences were more pronounced at the gingival margin. The control group specimens exhibited the least microleakage. There was no significant difference between thermocycled and non-thermocycled specimens for each category of materials used. There was, however, a significant difference between the experimental groups and the control groups. The dentin adhesives tested did not completely eliminate microleakage at the gingival margin of cervical cavities. PMID- 1299248 TI - Diagnosis of approximal caries: radiographic versus clinical examination using tooth separation. AB - This study compared the accuracy of clinical examination with bitewing radiographs and clinical examination using tooth separation to recognize the carious lesions activity. 336 bitewings were reviewed for approximal caries on the maxillary and mandibular second premolars and first molars of 168 high school students. Three examiners evaluated the radiographs using a megascope, a magnifying glass (x2) and an amplifying image screen. 77 surfaces were identified with approximal radiolucencies. After the radiographic examinations, the three examiners performed a conventional clinical inspection using a No. 4 odontoscope, a No.5 explorer probe and an air-water syringe with artificial light and relative isolation. The variables recorded were: (1) healthy surface; (2) white spot; or (3) carious cavitation. The separation method was performed with elastics. After 24 hours, the elastics were removed and the clinical examination conducted as in the non-separation group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299249 TI - Clinical comparison of Class V resin composite and glass ionomer restorations. AB - Three techniques for restoring abrasion/erosion lesions were evaluated over a 2 year period: 1) glass ionomer restoration (Ketac-Fil); 2) composite restoration with a dentin bonding agent (Silux Plus, Scotchbond 2); 3) composite restoration with glass ionomer liner and a dentin bonding agent (Silux Plus, Vitrebond, Scotchbond 2). There were 116 lesions restored and 115 evaluated for color match, cavosurface discoloration, surface texture, caries development, and retention. Most restorations were rated clinically acceptable for color match, cavosurface discoloration, surface texture, and caries development when measured at 2 years. Glass ionomer restorations and composite restorations with a glass ionomer liner and a dentin bonding agent demonstrated better retention rates, 97.4% and 100% respectively, than the composite restorations with a dentin bonding agent only (86.8%) (Cochrane Q test, P = 0.07). PMID- 1299250 TI - Marginal adaptation of castings made with dual-arch and custom trays. AB - This study compared the marginal fit of castings made with custom acrylic trays and metal or plastic dualarch impression trays. Standard clinical and laboratory procedures were used to make 36 gold castings for a metal tipodont die. Mean marginal openings were between 25 and 28 microns in all test groups. PMID- 1299251 TI - Microleakage of composite restorations with Syntac Bond and Denthesive. AB - The purpose of this study was to assess, in vitro, the microleakage of Class V restorations using two new dentin bonding agents with light polymerized resin composite. Restorations were placed in cavities prepared in extracted human premolars using either a bulk or incremental packing technique. Dentin bonding agents were applied according to the manufacturer's instructions. The enamel margin of each tooth was etched with 37% orthophosphoric acid. The teeth were stored for 6 weeks at 37 degrees C, thermocycled, and the restorations examined for leakage using methylene blue dye. The teeth were sectioned buccolingually through the restorations and the degree of microleakage assessed visually. All groups of teeth showed some degree of leakage at the gingival margin. There was a significant difference between the cavities restored by bulk packing of the resin composite and those where the resin had been applied incrementally for both materials (P < 0.05). There was no significant difference in leakage between the two dentin bonding agents (P > 0.05). PMID- 1299252 TI - Clinical evaluation of a heat-treated resin composite inlay: 3-year results. AB - The purpose of this study was to evaluate a resin composite inlay system in clinical trials involving human subjects. A total of 60 restorations were inserted equally in Class I and II preparations and in premolars and molars. A glass ionomer liner was applied to the dentin. Light-cured direct inlays were fabricated in the oral environment. Thirty inlays were heat-treated for 7.5 minutes at 125 degrees C in a dry heat oven. Enamel margins of the preparations were etched with 37% phosphoric acid gel. All inlays were cemented with a light cured enamel bonding resin. Restorations were evaluated using the USPHS system and M-L indirect scale. Six, 12, 24 and 36-month recalls were compared to baseline. Color, interfacial staining, secondary caries, and wear were unchanged from baseline for all restorations. Marginal integrity and surface texture show a differential change from baseline and with respect to restoration type. Indirect wear was not significantly different between restoration types (P < 0.05). Wear resistance was not significantly improved with heat treatment, but marginal integrity and surface characteristics showed marked improvement in the heat treated group at 24 and 36-month recalls. PMID- 1299253 TI - Clinical microleakage evaluation of a cavity varnish. AB - This clinical study evaluated the microleakage effectiveness of a cavity varnish when used in combination with two types of amalgam: a spherical particle and a dispersed phase alloy. Calcium hydroxide was utilized as the microleakage detection agent. Copalite showed a reduction in microleakage when it was employed with the spherical particle alloy used in this study. This study clinically demonstrated that Copalite is not totally effective in eliminating microleakage. PMID- 1299254 TI - Physical properties of a periodontal dressing material. AB - Further characterization has been undertaken of a visible light cured periodontal dressing material (Barricaid), which has been shown to exhibit superior physical properties to those of the standard (chemically curing) dressing materials. In particular, water sorption and solubility were studied, with a greater solubility found at 37 degrees than at 23 degrees with little further increase at 50 degrees C. Water sorption increased from 23 degrees C to 37 degrees C but decreased at 50 degrees C. Cure depth, determined by a penetrometer method, showed a constant resistance of 5.8 kg to probe penetration to a material thickness of 11 mm but resistance to penetrometer penetration, i.e. the level of cure, decreased sharply at greater thickness. The tensile strength of the material was unchanged when immersed up to 7 days in water at 37 degrees C, indicating a highly coherent material unaffected by water over a period corresponding to average clinical use. Previous studies showed that interlocking into the embrasures was required for adequate adhesion of Barricaid. To overcome this problem, teeth were etched and a bonding agent applied to the etched enamel surface. This chemo-mechanical lock gave an immediate adhesion value of 43.94 MPa, which decreased to 37.17 MPa at 7 days. The immediate adhesion value without etching and bonding was 34.23 MPa which decreased to 19.32 MPa at 7 days. Soaking decreased adhesion to enamel, but the effect was markedly less when the enamel was pretreated by etching and priming. PMID- 1299255 TI - Salivary pH while dissolving vitamin C-containing tablets. AB - Vitamin C is packaged in numerous forms which allow protracted exposure of the teeth to ascorbic acid. The repeated use of chewable mega dose tablets of vitamin C as a mint can damage the teeth by dissolving the enamel. In the time it takes to dissolve a chewable vitamin C tablet, a salivary pH drop takes place; salivary calcium and phosphorus ion concentration drops, and enamel dissolution may begin. Although sodium ascorbate, a buffering agent, is present in many vitamin C products, it may be added in insufficient quantity to be effective. With no apparent therapeutic value from topical vitamin C, vitamin C-containing products should be swallowed. PMID- 1299256 TI - Bond strengths of various materials to dentin using Amalgambond. AB - This study evaluated the bond strength of four restorative materials to dentin using Amalgambond. Two high-copper amalgams [Tytin; spherical, (T) and Epoque 80; lathe-cute, (E)], a gallium alloy [Gallium Alloy GF (G) and a resin composite [P 50 (P)] were tested. The polished dentin surface was treated with dentin-enamel activator (10 seconds), washed, dried, and adhesive agent was applied (30 seconds). In group A, the dentin adhesive was placed onto the dentin and while still wet, T, E, or G was condensed in cylinders (4 mm diameter) with condensation forces suggested by the manufacturer for a clinical situation. In group B, the cylindrical specimens of restorative material were allowed to set and then adhered to the treated dentin using the adhesive system. For the composite (control), the adhesive was applied to the treated dentin and while still wet, P was layered into the cylinder and cured for a total of 90 seconds. After storage in water (37 degrees C) for 24 hours, all the specimens were tested for tensile bond strength. This study revealed that the bond strength of P was significantly higher than the other materials tested and also that amalgam allowed to set for 1, 6 or 24 hours before adhesion to dentin had a significantly greater bond strength than freshly condensed amalgam. Although the desired high bond strength did not develop in the bonding of the metallic restorative materials, signs of bonding were found. PMID- 1299257 TI - Effect of rubber dam isolation on restoration deterioration. AB - The consequence of using either rubber dam or cotton roll isolation on the subsequent clinical deterioration of 546 polished amalgam and 148 anterior enamel bonded resin composite restorations was evaluated over periods of up to 15 and 10 years, respectively. Double-blind assessments for several clinical factors or parameters of the restorations were made using both direct and indirect observation methods. The transformed rating scores obtained were evaluated using a mixed model analysis of variance. With very few exceptions, all restoration placements were of high quality, and there were relatively few unsatisfactory rating scores given for any of the clinical factors assessed over the study. The low mean deterioration scores for most of the clinical factors assessed were also fairly similar, irrespective of the isolation method used. Therefore, although a statistically significant difference was found between the two isolation methods for marginal fracture of the composites, the clinical relevance of this difference is questionable. PMID- 1299258 TI - Pit and fissure sealing and mutans streptococci levels in saliva. AB - The effect of preventive pit and fissure sealants with a resin-based material on the number of salivary mutans streptococci was evaluated in 46 healthy 12-year old school children (F group) with medium or high counts during a 1-year study period. As controls served 33 children of the same age with the same bacterial levels at baseline (C group) and 55 children with low levels (L group). Caries prevalence and incidence were registered clinically and radiographically. Sealing of all accessible pit and fissures was carried out in the F group with a light cured Bis-GMA sealant. Bacterial levels at baseline and 3, 6, 12 and 52 weeks after treatment were estimated with a chairside method. The results disclosed a significant (P < 0.05) drop in the number of salivary mutans streptococci in the F and C groups at all sampling occasions compared to baseline. There were however no differences between the groups during the study period. Both the caries prevalence and incidence were significantly (P < 0.05) higher in F and C groups when compared to the L group. The results suggest that preventive pit and fissure sealing with a resin based material does not affect salivary mutans streptococci levels. PMID- 1299259 TI - Dentin surface treatment and shear bond strength of a light-cured glass ionomer. AB - This study evaluated the effect of dentin surface treatment with polyacrylic acid on the shear bond strength of Fuji Lining LC light-cured glass ionomer lining cement (GIC). A total of 40 human, noncarious extracted permanent molars stored in distilled water were used. A flat buccal dentin surface was ground wet on 600 grit silicon carbide paper. The teeth were then randomly distributed into four groups of 10 teeth each: Group 1: dentin rinsed with distilled water, dried with oil-free compressed air, placement of cylindrical GIC samples and sheared at 15 minutes post-curing. Group 2: same as group 1, but sheared 7 days post-curing. Group 3: dentin treated with GC Conditioner for 10 seconds, rinsed with distilled water, dried with oil-free compressed air, placement of the GIC and sheared 15 minutes post-curing. Group 4: same as group 3, but sheared 7 days post-curing. The GIC was mixed in a 1:1 powder-liquid ratio. The samples were stored in distilled water until sheared with an Instron. The results revealed that dentin surface treatment with the polyacrylic acid significantly increased the shear bond strength to dentin when tested at 7 days post-curing. PMID- 1299260 TI - Efficiency of protective sealants for glass ionomer cements. AB - This study compared the efficiency of protective sealants for glass ionomer cements. Scotchbond 2, Visar Seal, an experimental light activated silicone and Ketac Glaze were evaluated using liquid scintillation spectrometry. The results showed that Ketac Glaze was a very effective sealant for the newly placed glass ionomer cement and the resin component of Scotchbond 2 is in the same range. PMID- 1299261 TI - Should I upscale, downsize, or idle? PMID- 1299262 TI - [Regulatory aspects of modified release dosage forms]. PMID- 1299263 TI - Studies on the antibiotic resistance of Bacillus subtilis strains used in oral bacteriotherapy. AB - Bacillus subtilis antibiotic resistant strains used in oral bacteriotherapy were tested for the resistance to new therapeutically useful antibiotics. Chromosomal mutations originally selected in these strains proved to confer resistances also to these antibiotics. To investigate the stability of the antibiotic resistance markers present in B. subtilis O/C, T, N/R, SIN strains, we considered resistances to Chloramphenicol, Tetracycline, Rifampicin and Streptomycin. Resistances to Tetracycline, Rifampicin and Streptomycin were stably maintained for at least 200 generations in the absence of selective pressure. Chloramphenicol resistance proved to be inducible, showing a progressive loss when the resistant strain was grown in the absence of the antibiotic and a return to its original resistance levels after growth in the presence of the antibiotic. By in vitro and in vivo experiments we demonstrated the absence of homologous transfer of resistance markers among the resistant strains. PMID- 1299265 TI - Determination of alpha-tocopherol in semisolid gelled preparations by reversed phase HPLC. AB - Recently there has been increasing interest in alpha-tocopherol due to the possibility of its acting as a chemoprotective agent for skin cancer since it acts to protect dermic cells from the attack of free radicals caused by ionized radiations or chemical substances. To carry out this study, semisolid preparations were made from this active substance. We demonstrate a rapid, sensitive and reproducible method of extraction and analysis using an HPLC system with ultraviolet detection to carry out routine measurements beginning with hydrophilic gels of alpha-tocopherol. PMID- 1299264 TI - [Cyclopentenylalkylamine derivatives with analgesic and hypothermic activity]. PMID- 1299266 TI - A novel HPLC method for the determination of mitoxantrone in pharmaceutical formulations. AB - An HPLC method, using reversed phase chromatography, for the quantitative determination of mitoxantrone in pharmaceutical formulations has been developed. Rhein has been used as internal standard. PMID- 1299267 TI - Cytoplasmic membrane transplants in early Xenopus embryos indicate cell-cycle specific effects. AB - Fragments of rough endoplasmic reticulum or Golgi complex isolated from normal adult rat liver homogenates were injected into one cell of cleaving two-cell Xenopus laevis embryos and the effects on development were monitored during early cleavage by morphological analysis. Scanning electron microscopy revealed the formation of large cells on the injected side of the embryos. Such large cells were not present in controls and thus were considered to have been formed as a consequence of delayed cleavage. Delay of cleavage was obtained with as little as 1 ng of membrane protein giving a ratio of membrane protein to embryo protein of 1:10(5). Cytological observations of microinjected embryos confirmed the occurrence of delayed cytokinesis and suggested that nuclear division became asynchronous. Since rough microsomes from proliferating tissues (i.e., livers with primary tumors and livers undergoing regeneration) showed little or no effect on cytokinesis after microinjection into early embryos, we conclude that cytoplasmic membranes may exhibit cell-cycle-specific properties important for normal development. PMID- 1299268 TI - n-3 and n-6 polyunsaturated fatty acids have different effects on acyl CoA:cholesterol acyltransferase in J774 macrophages. AB - The effects of incubating J774 mouse macrophages with different fatty acids on cholesterol esterification were investigated. In cells incubated with n-3 polyunsaturated fatty acids, the rate of cholesterol esterification was significantly reduced compared with cells incubated with n-6 polyunsaturated fatty acids or with oleic acid. This change in cholesterol esterification appears to be the result of reductions in the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum of the macrophages incubated with the n-3 polyunsaturated fatty acids. No differences in microsomal cholesterol were observed among cells incubated with different fatty acids. However, cellular cholesterol levels were lower in cells incubated with n-3 polyunsaturated fatty acids. In microsomes from cells incubated with n-3 polyunsaturated fatty acids, both the Km and the Vmax of ACAT were lower than in microsomes from cells incubated with n-6 fatty acids or oleic acid. These findings may explain some of the reduction in atherosclerotic lesions that are observed with dietary fish oils that contain high levels of n-3 polyunsaturated fatty acids. PMID- 1299269 TI - Effects of amino acids and ethanolamine on choline uptake and phosphatidylcholine biosynthesis in baby hamster kidney-21 cells. AB - The effects of amino acids and ethanolamine on choline uptake and phosphatidylcholine biosynthesis in baby hamster kidney (BHK-21) cells were investigated. The cells were incubated with labelled choline in the presence of an amino acid or ethanolamine. The uptake of labelled choline was noncompetitively inhibited by amino acids. Glycine, L-alanine, L-serine, L leucine, L-aspartate, and L-arginine were effective inhibitors and a maximum of 22% inhibition of choline uptake was obtained with 5 mM glycine. Analyses of the labelings in the choline-containing metabolites revealed that the conversion of choline to CDP-choline and subsequently phosphatidylcholine was not affected by the presence of amino acids. The uptake of choline was also inhibited by ethanolamine in a concentration-dependent manner. Kinetic studies on the uptake of choline indicated that the inhibition by ethanolamine was competitive in nature. Although ethanolamine is a potent inhibitor of choline kinase, analyses of the labelings in the choline-containing metabolites indicated that the conversion of choline to phosphocholine was not affected in the cells incubated with ethanolamine. Ethanolamine did not change the pool sizes of phosphocholine and CDP-choline. Based on the specific radioactivity of CDP-choline and the labeling of phosphatidylcholine, the rates of phosphatidylcholine biosynthesis were not significantly different between the control and the ethanolamine-treated cells. In view of the concentrations of amino acids (millimolar) and ethanolamine (micromolar) in most cell culture media, it appeared that only amino acids were important metabolites for the regulation of choline uptake in BHK-21 cells. We conclude that both amino acids and ethanolamine have no direct effect on the biosynthesis of phosphatidylcholine. PMID- 1299270 TI - New expressions to describe solution nonideal osmotic pressure, freezing point depression, and vapor pressure. AB - New empirical expressions for osmotic pressure, freezing point depression, and vapor pressure are proposed based on the concepts of volume occupancy and (or) hydration force. These expressions are in general inverse relationships in comparison to the standard ideal expressions for the same properties. The slopes of the new equations are determined by the molecular weight of the solute and known constants. The accuracy and precision of the molecular weights calculated from the slope are identical and approximately 1% for the experiments reported here. The nonideality of all three colligative expressions is described by a dimensionless constant called the solute-solvent interaction parameter I. The results on sucrose have the same I = 0.26 for all three solution properties. The nonideality parameter I increased from 0.26 on sucrose to 1.7 on hemoglobin to successfully describe the well-known nonideal response of macromolecules. PMID- 1299271 TI - Inhibition of mammalian ribonucleotide reductase by cis diamminedichloroplatinum(II). AB - Ribonucleotide reductase is a highly regulated, rate-limiting activity in the synthesis of DNA. A previous study has shown that the Escherichia coli enzyme is inhibited by the clinically important antitumor agent cis diamminedichloroplatinum(II) (DDP), and this has led to the hypothesis that ribonucleotide reductase is an important site of action for this chemotherapeutic agent. This hypothesis has been directly tested in this investigation. We observed that DDP inhibits the mammalian ribonucleotide reductase, with 50% inhibition occurring at 0.3 mM. Unlike the E. coli enzyme where only one of the two protein components is targeted by DDP, we observed that both of the mammalian proteins (R1 and R2) were sites for the inhibitory activity of the drug. Colony forming experiments, enzyme activity studies, and analyses of R1 and R2 message levels in mutant cell lines containing either high levels of ribonucleotide reductase activity or exhibiting resistance to the cytotoxic effects of DDP were used to further investigate the potential role of ribonucleotide reductase in DDP cytotoxic action and drug resistance. These studies did not support a hypothesis formulated in the earlier investigation that inhibition of ribonucleotide reductase is an important component of DDP cytotoxic activity or that it is a major participant in DDP resistance mechanisms. From a biological point of view, DDP is a very active drug, and in addition to its cytotoxic effects it is capable of inducing a variety of cellular changes. Whether or not the inhibition of mammalian ribonucleotide reductase activity that we have described in this study plays a role in mediating any of these other effects remains to be determined. PMID- 1299272 TI - Induction and intracellular localization of the 80-kilodalton heat-shock protein of Neurospora crassa. AB - The most abundant heat-shock protein of Neurospora crassa is a multimeric glycoprotein of 80-kilodaltons (i.e., HSP80), induced strongly by hyperthermia and at a lower level by sodium arsenite, ethanol, and carbon source depletion. Immunoelectron microscopy, using indirect immunogold labelling demonstrated that HSP80 was undetectable in mycelium cultured at the normal growth temperature of 28 degrees C, but it appeared rapidly following the commencement of heat-shock treatment at 48 degrees C. HSP80, visualized by the gold label, was observed almost exclusively in the cytoplasm, exhibiting a uniform distribution. Association of this protein with cellular membranes and (or) targeting to a particular subcellular compartment or organelle was not apparent. PMID- 1299273 TI - Overexpression of SPARC in stably transfected F9 cells mediates attachment and spreading in Ca(2+)-deficient medium. AB - The Ca(2+)-binding protein SPARC is one of a group of proteins that function in vitro to promote the rounding of cells. To assess whether the modulation of cell shape by SPARC is affected by extracellular Ca2+, we used F9 cell lines that had been stably transfected with sense or antisense SPARC DNA. Sense-transfected (S) lines that overexpress SPARC are aggregated and rounded, whereas antisense (AS) lines that express low levels of the protein are flat and spread. We tested whether the cell lines would exhibit these altered morphologies in Ca(2+) deficient media. When cultured under these conditions, S lines attached and spread, whereas AS lines attached but remained round, with no subsequent spreading. Addition of CaCl2 or purified SPARC to the Ca(2+)-deficient medium resulted in spreading of the AS and control lines and a reappearance of the altered morphologies. Expression of the Ca(2+)-binding cadherin uvomorulin by the cell lines correlated with neither their morphology nor their level of SPARC expression. We conclude that the altered phenotypes of the transected lines reflect, in part, the concentration of extracellular Ca2+ and that the spreading exhibited by the S lines under Ca(2+)-deficient conditions is directly related to their enhanced expression of SPARC. SPARC might, therefore, mediate interactions between cells and matrix that are permissive for adhesion when levels of extracellular Ca2+ are diminished. PMID- 1299274 TI - Soluble endothelin degradation enzyme activities in various rat tissues. AB - From soluble extract of rat kidney we have previously identified an endothelin degradation enzyme that rapidly and specifically cleaves off the C-terminal tryptophan of endothelin-1, resulting in a peptide that is three orders of magnitude weaker in potency than endothelin-1 in causing smooth muscle contraction. The tissue distribution of this enzyme was examined, and the soluble extracts of rat kidney were found to contain the highest enzyme activity, followed by the spleen and the liver. In contrast, no enzyme activity was detected in the soluble extracts of brain, heart, and lung. The biochemical properties of the partially purified enzyme from kidney were further investigated. The optimal pH of the enzyme was between 5 and 7. The endothelin degrading activity was effectively blocked by thiol protease inhibitors such as benzyloxycarbonyl-Phe-Ala-diazomethyl ketone and p-hydroxymercuribenzoic acid, as well as by phenylmethylsulfonyl fluoride, but not by metalloprotease and other serine protease inhibitors. This enzyme displayed a clear difference in substrate specificity when compared with other thiol proteases such as cathepsin B, cathepsin H, and cathepsin L, known to be present in the kidney. These results suggest that a novel protease with endothelin degrading activity is widely distributed in a number of tissues. PMID- 1299275 TI - [Histotopographic study of the pharyngoesophageal junction in newborns]. AB - In the present work the importance of the cricopharyngeal muscle as the main constituent of the pharyngoesophageal sphincter is showed. Some aspects traditionally admitted by the classic anatomic descriptions and some hypothesis about the function of this part of the aerodigestive pathway are discussed. PMID- 1299276 TI - [Unusual congenital laryngeal anomalies: a review of 13 cases]. AB - In this study we presents: 6 subglottic stenosis, 2 subglottic hemangiomas, 2 laryngeal webs, 2 laryngeal cysts and 1 laryngoesophageal cleft. Were diagnosed during laryngotracheobronchoscopies performed to 220 newborns and small children that showed as main finding: stridor, voice change or aspiration syndrome. The stenosis, hemangiomas and cleft were resolved spontaneously. In the webs and cysts surgical correction was required. Here we will expound upon clinical, diagnostical and therapeutic aspects of these rare congenital laryngeal anomalies. PMID- 1299277 TI - [Correlation between audiometric and electronystagmographic results in Meniere's disease]. AB - Cochlear and vestibular functions of 30 patients suffering from Meniere's disease have been analyzed through audiometric and electronystagmographic studies. Auditive thresholds in low, medium and high frequencies have been correlated with the results of the caloric and pendular tests. Statistical analysis has demonstrated that there is no significant relationship between caloric and pendular reflectivity and hearing loss in the mentioned frequencies. In conclusion, in Meniere's disease hearing losses and vestibular alterations follow a different pathologic pattern. PMID- 1299278 TI - [Smell during speleologic isolation]. AB - A smell evolution it is done from two isolation experiences, in a cave by a speologyst in Eastern Pyriness. The investigation verified the smell recovery from a person who is used to living in town with big pollution. This work was done with twenty four fragrant essences, twenty of them were oriented to olfactory nerve exploration and four of them to trigeminal response. These tests were done with each nostril separately. PMID- 1299279 TI - [Computerized tomography evaluation of laryngeal paralysis caused by recurrent nerve involvement]. PMID- 1299280 TI - [Comparative study of histology and flow cytometry results obtained in 2 groups of laryngeal tumors, glottic and supraglottic, in T-1 stage]. AB - We studied histophatological parameters and DNA content in 27 supraglottic and 37 glottic T-1 squamous cell carcinoma of the larynx. The DNA content was determined by the Hedley method in paraffin-embedded sections of formalin-fixed blocks in an EPICS Profile flow cytometer. We studied 14 histopathological parameters and only 3 were statistically different in both groups of tumors: Differentiation, infiltrative degree and mitoses. There weren't statistical differences in DNA content (DNA index and proliferation index). PMID- 1299281 TI - [Epithelioma of the pyriform sinus: retrospective study and survival analysis after 5 years]. AB - We have studied 27 clinical records of patients with piriform sinus epidermoid carcinoma diagnosed and treated in our department during a period of 6 years. All the patients underwent surgery and radiotherapy. We have analyzed the survival and recurrence rates together with other parameters that may have some influence in them. We have tried to show the factors that might be in relation with the prognosis of pyriform sinus carcinoma. The statistical analysis show a survival rate of 29.6% after 5 years follow up, being the node invasion, wither clinical or histological, the main fact to have a prognostic value. PMID- 1299282 TI - [Oral hairy leukoplakia in human immunodeficiency virus positive patients: clinical and etiopathogenic aspects]. AB - Clinical and etiopathogenetic features of oral hairy leukoplakia in 5 patients positive for Human Immunodeficiency Virus were studied. Oral hairy leukoplakia were located on the lateral borders of the tongue and showed a corrugated/hairy aspect in all the cases. Histological examination showed hyperparakeratosis, acanthosis, hair like projection (n = 4) koilocyte-like-cells and moderate subepidermal inflammation. Immunohistochemistry revealed positive results for Epstein-Barr virus indicating an active replication of this virus within the epithelial cells of the stratum granulosum and upper stratum spinosum. PMID- 1299283 TI - [Interaction between hypertriglyceridemia and noise in human hearing]. AB - We carry out a cross-sectional study on 1205 workers exposed to industrial noise. After the clinical, analytical and audiological examination, we can't demonstrate any influence of hypertriglyceridemia on noise induced hearing loss. We get a statistically significant relationship between noise and hearing loss only in the group of workers with normotriglyceridemia. PMID- 1299284 TI - [ORL emergencies at a health center: a study of the incidence during 1990]. AB - We present a retrospective study of 942 ENT emergencies in a Health Center (primary care), during the year 1990, treated by family physicians. They are analysed under different parameters such as date, time, sex, age, diagnosis, drug prescription and dispatch of the patients to the hospital. We carried out an analysis of the quality of the attention given. PMID- 1299285 TI - [Homotransplants in cervical trachea: clinical and histopathologic results]. AB - An experimental study about homotransplant of cervical trachea in Wistar rats is presented. Surgical approachment consists in excision of 7 or 9 tracheal rings and their posterior end-to-end anastomosis. The animals are divided in two groups. In the first one an homotransplant of cervical trachea is practised and compared with the second one as control group. Clinical and histopathological results are similar in both groups. Our findings are also discussed, comparing with other authors. PMID- 1299286 TI - [Primary tumors of the external auditory canal]. AB - Primary tumors of the external auditory canal (EAC) are rare, their etiology is uncertain and their prognosis, dim. The most effective therapy combines both surgery and radiotherapy. This study reviews the literature and shows the results from 13 cases, treated between 1981-1991. This series proves a clear prevalence for the epidermoid tumors (10 out of 13) and we call the attention on their poor prognosis even in those tumors confined to EAC. The types of treatment and their complications as well, were reviewed. PMID- 1299287 TI - [Supraclavicular schwannoma with malignant cytologic appearance]. AB - We present the case of a old woman with a supraclavicular mass and sarcomatous cytologic appearance. The final microscopic appearance was schwannoma. We also review the pertinent literature. PMID- 1299288 TI - [Follicular adenoma in lingual thyroid: report of a case]. AB - We present a case of follicular adenoma which has its origin in a unique lingual thyroid. The interest lies in the oddity of this pathology and in the unusual clinical form of dysphagia. In spite of the fact that the thyroid ectopy is a congenital anomaly in the development of the thyroid, the history of previous administration of cervical radiotherapy and the diagnosis in an elderly person makes us suppose, in this case, that there is a different etiopathology. PMID- 1299289 TI - Three composite finishing systems: a multisite in vitro evaluation. AB - Selection of appropriate finishing and polishing devices is critical to the optimal appearance and longevity of composite resin restoratives. This report compares the effectiveness of three specific finishing and polishing systems when used to prepare the surfaces of composite restorative materials provided by the respective manufacturers. Profilometer surface roughness analyses were conducted at two separate laboratories to cross-correlate numerical smoothness data in this study. Statistically significant differences in mean surface roughness were found between various finishing system/composite resin pairings. Surprisingly, a hybrid composite resin finished and polished with its respective finishing/polishing system gave a significantly smoother surface than a microfill composite surface prepared with its corresponding sequentially coated abrasive disc system. This finding was corroborated at a second site using a separate methodology for profilometer analysis. PMID- 1299290 TI - Bite forming of occlusal composite restoration. AB - The bite-forming technique of posterior composite restoration is presented. Before preparation, the tooth surface is coated with a separating varnish. The occlusal anatomy of self-cured composite is bite formed by bare opposing teeth. Subsequent finishing is considerably simplified by the ability to peel excess composite from the varnished tooth surface. Finishing and detailing are further simplified by use of top-cut and top-safe superfine diamond points. A "free matrix" is used for Class II restorations. PMID- 1299291 TI - Indirect porcelain veneer technique for restoring intrinsically stained teeth. AB - Indirect porcelain veneers are often the ideal restoration for intrinsically stained teeth. This article details a step-by-step procedure for esthetically restoring discolored teeth. Porcelain laminate veneers are often indicated when teeth bleaching or direct composite bonding procedures cannot provide the desired esthetic result. Veneers are more appealing to many patients than full coverage crowns because of the more conservative tooth preparation required. If technique details are followed meticulously and cases are appropriately selected, porcelain veneers are not only durable but also promote marvelous gingival health and may be the most esthetic anterior dental restoration. PMID- 1299292 TI - Effect of thermocycling times on dentin bond strength. AB - Thermocycling is widely used in the evaluation of dentin bonding agents. The purpose of this study was to determine the effect of increasing thermocycling times on the shear bond strength of composite resin to dentin using a NTG GMA/BPDM-type bonding agent. Fifty human molar teeth were ground flat on the buccal surface into dentin (600 grit). Ten specimens were prepared for each thermocycling group of 100, 500, 1000, 2000, and 4000 cycles. The adhesive agent was applied to the dentin according to the manufacturer's instructions. A cyclindrical-shaped matrix was used to form the composite resin that was light cured to the treated dentin surface for 60 seconds. Thermocycling was started after 24 hours of storage in deionized water at 37 degrees C. Shear bond strengths were determined with an Instron universal testing machine at a cross head speed of 0.5 mm per minute. The bond strengths in megapascals (MPa) were : 100 cycles 18.1 (+/- 5.2) MPa, 500 cycles 19.4 (+/- 4.0)MPa, 1000 cycles 16.5 (+/ 2.9), 2000 cycles 14.6 (+/- 5.1), and 4000 cycles 19.9 (+/- 3.2)MPa. When this data was subjected to an ANOVA, no significant difference was found between the groups. PMID- 1299293 TI - Bonding amalgam to tooth structure: a scanning electron microscope study. AB - The purpose of this scanning electron microscope study was to observe the interface between dentin and amalgam utilizing various adhesive resin cements. The adhesive resin materials used in this study were Imperva Dual, Geristore, and Panavia. The scanning electron micrographs revealed that bonds were established between amalgam, adhesive resins, and dentin. PMID- 1299294 TI - Two-step provisional technique for onlay preparations. AB - Compared to full crown temporization, direct autocured resin provisional technique for intracoronal onlay preparations is more complicated and less predictable. Clinical concerns include possible pulpal irritation, extra chair time for contouring proximal and marginal excess, and a critically short time constraint to remove the curing resin in the "rubbery stage" to avoid distortion or "locking" into the preparation. A two-step direct technique using two new light-cured provisional resins addresses these problems. First, a light-cured, elastic resin is condensed against the internal preparation walls and confined within a wedged metal matrix band. Then, using a clear template matrix, the elastic foundation is overlaid with a strong and esthetic light-cured provisional resin. PMID- 1299295 TI - Esthetic posterior restorations: direct composite resins. PMID- 1299296 TI - [Insurance medicine and accident surgery]. AB - A definition of insurance medicine is presented with due consideration for national peculiarities (social insurances) in Switzerland. The historical development from original trauma-directed accident medicine to the present-day insurance medicine with its more comprehensive nature is shown with particular consideration being given to the close connection with traumatology (trauma surgery/orthopaedic surgery). The guarantee of smooth-running and constructive cooperation between traumatologists and welfare organizations is one of the major tasks of doctors employed in insurance companies, whose sphere of influence and qualifications are under discussion. PMID- 1299297 TI - [The deltoid flap-plasty. Therapy of choice in large rotator cuff ruptures?]. AB - Rotator cuff tear is an extremely common and important disease. An extensive rotator cuff tear is an incapacitating event and remains a major problem which forces to respect to the management. The late outcome of majors ruptures of such tears are often a defect-arthropathy with a complete destroy of the shoulder and a loss of flexibility caused by pain. The deltoid muscle plasty, as the logical reconstruction method and relatively easy to perform, lead to better results in compare to all the variety of surgical treatments of restoring the anatomical continuity. This article reviews the clinical manifestations, operative technique and the results associated with the treatment by deltoid muscle plasty. Based on the results. Based on the results of flexibility, and postoperative pain in shoulder we conclude that the early results in our group of the first 20 patients are excellent. 84% of the patients were subjectively very satisfied and free of pain. PMID- 1299298 TI - [Results of surgical management of scapula fractures. 78th Annual Meeting of the Swiss Society of Accident Surgery and Occupational Diseases, 4-5 September 1992 in Olten]. AB - The follow-up of 8 patients with scapular fractures showed a high rate of complications with 3 infections and problems with the osteosynthetic material. This did not effect the results in any case, most results were good. The indication for the operation should be proved restrictively, the following operative treatment should be minimal invasive. CPM-devices were used after operation and had a positive effect. PMID- 1299299 TI - [Post-traumatic impingement syndrome caused by a displaced tuberculum majus fragment]. AB - The posttraumatic impingement-syndrome caused by displacement and retraction of the entire great tuberosity with the bony insertions of the supraspinatus or infraspinatus muscle is often diagnosed with delay. Two types are distinguished: 1. The fracture of great tuberosity with proximal and dorsal dislocation of the fragment impairs motion by impinging under the acromion and against the posterior glenoid wall. 2. The multi-fragment bony fracture at the rotator cuff insertion, usually finish in rotator cuff deficiency. The analysis of the last 22 operated patients demonstrates the important preoperative complaints, commonly during a long time before reconstruction. The excellent postoperative results show the importance of the early and generous management of proximal humeral fractures. PMID- 1299300 TI - [Experiences with conservative therapy of humerus shaft fractures]. AB - A well proved method for the conservative treatment of fractures of the humeral shaft is clearly shown by words and pictures. A study of 36 own cases during the years 1985 up to 90 informs on the problems of conservative treatment of these fractures. Even if there is a perfect primary reposition, impossibility of proper retention in the plaster cast may lead to post-primary osteosyntheses (2 cases in 36). Despite correct conservative treatment there are always delayed unions in a certain percentage (6 cases in 34), which you can't recognize before 3 months after injury, but then should bring them to operative treatment. There is quite a high number of pseudarthroses (4 cases in 32). It is still unclear, which type of fracture and which type of patient is going to build up a pseudarthrosis. In conservative treatment, the most important thing is--compared to operative treatment--a very closed and carefully observing aftercare. PMID- 1299301 TI - [Primary closure of traumatically ruptured bursae]. AB - Normally a bursectomy is the choice of therapy when a bursa of a joint is opened through trauma. A primary closure was performed on 10 patients, selected according to certain specific criteria. Nine out of ten cases showed no complications with good short and long-term results. PMID- 1299302 TI - Effect of hypothermia on focal experimental seizures. AB - The effect of general hypothermia was investigated in 15 unanesthetized cats. The animals were immobilized with Flaxedil and maintained on mechanical respiration. An epileptogenic focus was induced by stereo-tactical injection of penicillin to the right hippocampus. Cooling of the body was followed by a marked decrease of the amplitude and frequency of the penicillin spikes. The antiepileptic effect of general hypothermia was not dependent on brain stem section as suggested by previous investigations. Seizures generated by a hippocampic penicillin focus were more resistant to hypothermia than discharges produced by penicillin applied to the visual cortex. PMID- 1299304 TI - A trial to apply the concept of genomic imprinting to the manic-depressive illness. AB - The phenotypic indicators of genomic imprinting were applied to the familial psychopathology data collected through the family history method about 886 adult relatives of 65 manic-depressive probands directly investigated. The probands and their relatives were diagnosed according to DSM-III/DSM-III-R criteria. A first analysis of the age at onset of the BP illness by affective status of the probands' parents suggested that the BP disorder begins about 8 years earlier in the probands whose father was affectively ill (13.84% cases) than in the probands whose mother was affectively ill (24.6% cases) (t = -3.29, P < .004). When controlling this result for the effect of the probands' sex, its statistical significance decreased. The severity of the BP illness seemed also to be influenced by the affective status of the probands' father but only when assessing the probands' illness severity over a long time period and taking into account their psychosocial functioning; the number of manic and depressive hospitalized and non-hospitalized episodes as a single measure of the BP disorder severity as well as the morbidity risk in the first degree relatives of the probands did not significantly differentiate the patients whose disorder was transmitted by the father/paternal side as compared with the patients who inherited the BP disorder from the mother/maternal side. PMID- 1299303 TI - Habituation of orienting reaction in therapy-resistant generalized epilepsy. AB - A polygraphic study on resistance to habituation of the somatic, autonomic and EEG components of the orienting reaction elicited by a repetitive auditory stimulus was performed in 39 epileptics with therapy-resistant generalized seizures (TRGS) and in 119 matched subjects in two control groups. The study showed a significantly higher resistance to habituation of the orienting reaction in epileptics with TRGS vs. the normal subjects of control group I. A significantly higher resistance to habituation was also noted in epileptics with therapy-controlled generalized seizures of control group II. The correlational analysis of data showed that the severity of these habituation disturbances in epileptics with TRGS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the habituation disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal habituation disturbances, the effect being the more marked as the treatment was more sustained. The above-mentioned habituation changes in epileptics with TRGS should be ascribed to some disturbances in nervous excitability. PMID- 1299305 TI - A personal neurosurgical procedure and an illustrative angiographic sign in indirect cerebral lacerations caused by temporo-frontal traumata. PMID- 1299306 TI - Neuro-oncogenesis. A review. PMID- 1299307 TI - REM narcolepsy, clinical polysomnographic and computerized electroencephalographic studies. AB - Clinical and polysomnographical investigations have been performed in 35 patients with REM narcolepsy (group 1), comparatively with 45 patients suffering from symptomatic hypersomnia in NREM sleep (group 2). The polysomnographical recordings have been made by: a) continuous recording covering 24 h; b) submission of the subjects to the "Maintenance of wakefulness tests" (MWT). In 20 narcoleptics and in 12 normal subjects, computerized EEG mappings were performed in wakefulness and in different sleep stages. In the narcoleptic patients, the association of the sleep attacks with other symptoms of Gelineau's disease has been noticed. The 24 h continuous polysomnographical recordings pointed out relevant differences between the first and the second group: the patients with REM narcolepsy (Gelineau's disease) presented increased quantities and percentages of REM sleep and manifested several periods wish sleep-onset REM. Comparatively, the patients with NREM hypersomnias slept predominantly in NREM sleep, and presented normal percentages of REM sleep and also manifested sleep onset NREM periods. One found great differences between the two groups by the MWT, that is, in the first group the mean values of REM sleep were greater, the REM latency and the sleep latency were very short and one assisted to many sleep onset REM. The cortical EEG mappings were ampler and slower on the right posterior temporal and occipital regions (especially during the REM sleep) either in normal or in narcoleptic patients. These results suggest the consistency of some previous data regarding the differentiation of the true REM narcolepsy (as an independent entity) from the various frequent NREM hypersomnias. PMID- 1299308 TI - Traumatic intracerebral hematoma. A report of 50 cases. AB - The study presents an analysis of demographic, clinical and paraclinical characteristics of 50 cases as well as the surgical treatment results of 50 cases with traumatic intracerebral hematoma (TIH) out of 70 admitted. The men showed the greatest incidence, the male/female ratio was 5:1. Age mean was 55.3 yrs. Hematomas were caused in one third of the cases by traffic collisions, followed by severe cranial traumata associated or not with other traumatic lesions and/or preceding diseases. The most frequent location was anterior in the frontal (30%) and temporal lobes (26%). Diagnosis was confirmed by arteriography and tomography. Specific paraclinical aspects of TIH were discussed together with those of the primary intracerebral hematoma (PIH). All patients were operated on under general anesthesia. A minimum craniectomy was carried out aimed at the lesion. Surgery was planned after a full neurological examination. Postoperative mortality was increased (42%) due to the severity of trauma (88%) in patients with a Glasgow coma scale assessment under 8, to age (50% of the patients were over 50 yrs), to hematoma size (84-100% in patients with a diameter of the hematoma between 50 and 100 cu cm, and over 100 cu cm, respectively) and to the location (66% in the frontal hematomas compared to 33% in temporal ones). PMID- 1299309 TI - Genetic studies in three South American black populations. AB - Twenty-one genetic systems were investigated in three relatively isolated South American Black populations. Unexpected allele frequencies were found in different systems in all populations, suggesting the occurrence of genetic drift and/or founder effects. The estimates of racial admixture indicate 50% to 79% of Black ancestry, with various degrees of White (18%-28%) and Amerindian (3%-32%) ancestry. PMID- 1299310 TI - Genetic polymorphism of red cell membrane band 3 in Japanese Brazilians. AB - Limited proteolysis of intact red cells has been shown to yield peptides of 60 kDa and, in some individuals, 63 kDa, from the band-3 membrane protein. In a random population sample of 117 Brazilians of Japanese origin, the allele frequencies of the band-3 variants were p60 = 0.889 +/- 0.0205 and p63 = 0.111 +/ 0.0205. The phenotype frequencies fit the Hardy-Weinberg equilibrium for the hypothesis of three phenotypes controlled by two codominant alleles of a single autosomal locus. The frequencies of the alleles in this population of Japanese ancestry are highly different from those of Brazilian Caucasoid blood donors but rather similar to those of Brazilian Negroid donors. PMID- 1299311 TI - Distribution of PGM1 subtypes in 12 populations of China. AB - The distribution of PGM1 subtypes in 12 populations of China was studied by using isoelectric focusing (IEF) in 0.5 mm thick polyacrylamide gel, pH 5-7. It was found that the PGM1*1A frequency was higher in northern China and lower in the south. Phosphoglucomutase (PGM: E. C. 2. 7. 5. 1) occurs in all human tissues and is controlled by four autosomal loci, i.e., PGM1, PGM2, PGM3 [Hopkinson and Harris 1968] and PGM4 [Cantu and Ibarra 1982]. The Polymorphism at the PGM1 locus in human was first revealed in 1964 [Spencer et al 1964]. Since then, extensive studies showed that two codominant alleles, PGM1*1 and PGM1*2, are present on locus PGM1 in all populations, as well as many rare alleles. Investigations with isoelectric focusing (IEF) revealed the presence of four common allotypes, which were previously labelled as PGM1*1+, PGM*1-, PGM*2+, PGMI*2- [Bark et al 1976]. The workshop, held in West Germany in 1985, recommended a new nomenclature: PGM1*1A, PGM1*1B, PGM1*2A and PGM1*2B instead of PGM*1+, PGM1*1-, PGM1*2+ and PGM1*2- in order to avoid misunderstanding [Dykes et al 1985]. A large body of data on the distribution of the four common PGM1 alleles in different populations in the world has been accumulated. But the data on PGM1 in China are yet very limited. The present paper reports the PGM1 gene frequencies in 8 national minorities and 4 subpopulations of Han in China. PMID- 1299312 TI - The genetic composition of an endogamous Adi-Dravidar population of Tamil Nadu. AB - A total of 204 blood samples were collected from healthy, unrelated Adi-Dravidars of Chengalput District, Tamil, India. These samples were screened for ABO and RH blood groups using the respective antisera. CP and ALB serum protein electrophoretic phenotypes were assessed. The chi 2 analysis for Hardy-Weinberg equilibrium revealed that the population fits in panmictic equilibrium. The results were compared with the findings reported for other populations of Southern India. PMID- 1299314 TI - Phosphoglucomutase 1 (PGM1) subtypes and ESD types in mothers and newborns from the island of Tasmania, Australia. AB - PGM1 subtypes and ESD phenotypes of 600 mothers and their respective newborn infants residing in the northern part of the island of Tasmania were examined. The allele frequencies of PGM1 in the mothers were 1+ = 0.6525, 1- = 0.1250, 2+ = 0.1758 and 2- = 0.0467, and in the newborns were 1+ = 0.6675, 1- = 0.1275, 2+ = 0.01600 and 2- = 0.0450. Both samples were found to exhibit Hardy-Weinberg equilibrium conditions and there was no significant difference between them. Also, the frequencies of PGM1 alleles were overall similar to frequencies in neighbouring populations on the Australian mainland. The frequency of ESD*2 in both samples was similar (0.105) but the mothers' genotypes were not in Hardy Weinberg equilibrium (due to an excess of type 2). The ESD allele frequencies in Tasmania are similar to those reported in other white Australian populations. PMID- 1299313 TI - Genetic serum protein polymorphisms in Jordanian Arabs: a pilot study of the systems AHSG, BF, F XIII B, GC, PI, PLG and TF. AB - A sample of 124 healthy unrelated Arabs from Amman, Jordania were studied for AHSG, BF, F XIII B, GC, PI, PLG and TF serum protein markers. The more recently discovered systems AHSG, F XIII B and PLG appear to be very useful for the characterization of Near Eastern populations. PMID- 1299315 TI - Low frequency of isozyme 2 acid a-glucosidase in Greece. AB - The isozyme type 2 of acid a-glucosidase, identified by "affinity" starch gel electrophoresis, was found to have a gene frequency of 0.001 in an unselected Greek population from Southwestern Greece. The estimated frequency of the heterozygote in the population is 1 in 500 and of type 2 homozygote 10(-6). This frequency is by far lower than that reported in Europeans and other populations. This may be a characteristic of the Greek gene pool at the acid a-glucosidase locus or it may be present in populations of neighbouring countries as well. PMID- 1299316 TI - Beta-thalassaemia mutations and the underlying beta gene cluster haplotypes in the Greek population. AB - The polymorphic sites across the beta gene cluster (restriction haplotypes) in association with specific thalassaemic mutations were analyzed in representative samples of normal and thalassaemic Greeks in comparison to similar data of other populations around the mediterranean basin. We studied 316 normal chromosomes, 218 chromosomes from patients with thalassaemia major and 72 chromosomes from patients with thalassaemia intermedia. In the former group, haplotype frequencies followed the order I, IX, II, V etc.. In the group of patients with transfusion dependent thalassaemia the order was I, II, V and VI, while in those with thalassaemia intermedia the most frequent haplotypes were I and VI. The frequency of haplotypes I and VI was higher among the thalassaemic chromosomes in comparison to those of the normal population; haplotype IX showed the inverse relation. These findings imply that the thalassaemic mutations occurred at a very early stage on haplotypes I and VI and much later on haplotype IX. Micromapping did not reveal any significant variations. Haplotypes I, II, V and VI were associated with the molecular defects IVS-1 nt 110, beta zero-39, IVS-1 nt 1 and IVS-1 nt 6 respectively. A number of other mutations were also identified. The molecular defect was identified also on a random sample of beta-thalassaemia carriers (424 chromosomes). On the basis of the overall data, the feasibility of prenatal diagnosis of thalassaemia by allele specific hybridization is ca. 80%, with the four most common oligomers and 95% when the set of probes expands to eight. PMID- 1299317 TI - Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Albanian ethnic minority of Cosenza province, Italy. AB - The Albanian ethnic minority of the Cosenza province (Calabria, Southern Italy) is constituted by a population of 42,305 inhabitants living in 19 communes. The first presence of this population, in Southern Italy, dates back to the fifteenth century as a result of different immigrations. We have studied the G6PD in the population of this province by determining both the frequency of the G6PD deficiency and the type of Gd(-) alleles in samples from 19 communes. The overall frequency estimate turned out to be 0.0294 and those of the 8 highland communes and of the 11 communes located in the valleys were 0.0242 and 0.033 respectively. Both the frequencies and the ratio between the frequencies of the different Gd(-) alleles are significantly different with respect to a previous study carried out on the non-Albanian population of the same areas. The high endogamy rate found among the grandparents' and among the parents of the probands living in the Albanian community, shows that this community is to a large extent reproductively isolated from the neighbouring populations, thus accounting for these differences. PMID- 1299318 TI - Polymorphism of ABO, MN, rhesus and P blood groups among four east Georgian populations. AB - Phenotype and gene frequencies of ABO, MN, Rhesus(D) and P blood group markers have been studied among four samples of East Georgian populations (Kaspi, Kareli, Gurdzhaani and Lagodekhi). The results indicate that they do not differ from other neighbouring Georgian populations. PMID- 1299319 TI - Plasminogen (PLG) gene frequencies in the Iberian Peninsula: heterogeneity analysis. AB - The distribution of Plasminogen (PLG) phenotypes in five populations of Spain (Galicia, Castilla-La Mancha, Castilla-Leon, Extremadura and Western Andalucia) is analysed by means of polyacrylamide gel isoelectric focusing and immunofixation. PLG*A frequencies, ranging from 0.7281 in Extremadura to 0.8038 in Castilla-Leon, are similar to those reported for other Southern populations of the European continent and higher than those in Northern and Central European populations. Heterogeneity analysis of the PLG allele distribution among different regions of the Iberian Peninsula have also been carried out. PMID- 1299320 TI - Variability of the Rh system in a central Pyrenean population (Aran Valley). AB - This work describes the results of a survey on the Rhesus system carried out in the autochthonous population of Aran Valley, a small and rather isolated region on the Northern side of the Central Pyrenees. Also, a comparison is made with other geographically and historically related populations in order to discuss the data in terms of the historical origin of this population. The data obtained shows a good agreement between observed and expected values in Hardy-Weinberg equilibrium. The Aranese population also reveals some peculiarities concerning some haplotypes. The comparison with European and non European Mediterranean populations shows a clear genetic distance from Basque populations, and a relative proximity with presumably Celtic ones. PMID- 1299321 TI - The control of cholesterol metabolism and plasma lipid levels in infant rats. AB - Infant rats received an i.p. injection of insulin, anti-insulin serum, streptozotocin, antiglucagon serum or dexamethasone. All substances except the antiinsulin serum, raised the plasma triglyceride level. Both antisera decreased plasma cholesterol levels, while streptozotocin, insulin and dexamethasone caused an increase. The activity of 3-hydroxy-3-glutaryl CoA reductase in liver and brown adipose tissue changed inversely to the cholesterol level. However, small intestinal enzyme activity was increased by insulin administration inspite of the rise in plasma cholesterol. PMID- 1299322 TI - Influence of casein and soy flour proteins on aminoacid content in the liver of experimental animals. AB - We have observed a significantly increased content of fats and decreased content of proteins in the liver of experimental rats fed a diet supplemented with 25% casein proteins in comparison with the application of de-fatted soy flour. Casein proteins have a higher content of methionine in relation to cystine than baked soy flour. But the soy diet in contrast to the casein diet has a high content of free aminoacids which are not present in casein at all: aspartic acid, asparagine, alpha-aminoadipic acid, methionine, norleucine, lysine, phenylalanine, beta-alanine, ethanolamine, histidine, proline, gamma-aminobutyric acid, taurine. Differences in free valine, alanine, arginine, glycine, ornithine and cysteic acid are also significant. The content of free aminoacids in the liver of experimental animals fed a soy diet is high in the content of cystine, cystathionine, ornithine, beta-aminoisobutyric acid, beta-alanine, gamma aminobutyric acid, leucine. We have also found accumulation of methionine, glycine, alpha-aminobutyric acid, taurine and citrulline in free aminoacids from the liver of animals fed a casein diet. Citrulline and glycine in free aminoacids from the liver of animals fed a soy protein supplement were not recorded. Our investigations have shown that the application of a soy diet enriched with cystine acts protectively on methionine and that methionine is preferentially utilized for protein synthesis. The catabolic pathway of methionine prevails in animals on a casein diet. PMID- 1299323 TI - Thymus lipids in continuously irradiated rats. AB - Male Wistar rats were irradiated continuously with a daily dose of 0.19 Gy (120 days), 0.57 Gy (90 days) and 0.96 Gy (35 days) of gamma rays. An other group of rats was irradiated continuously with graded doses of gamma rays, up to total exposures ranging from 3.83-19.15 Gy. Depending on both the daily dose and total exposure, there was a decrease in phospholipid content in the thymus which correlated well with thymus weight changes. The decrease in triacylglycerol content was a less reliable sign of radiation damage. The phospholipid content reflecting the patterns of organ cellularity is a valuable indicator of the extent as well as recovery from radiation-induced injury to the thymus. PMID- 1299324 TI - The vectorcardiographic QRS loop in pulmonary ventilation alterations in young healthy women. AB - The influence of some pulmonary ventilation alterations (the normal ventilation at rest = control), the hyperventilation (HV) lasting 75 s, the hypoxic hypercapnic ventilation (HXV) lasting 3 and 6 min) on the instantaneous QRS vectors was investigated in 42 young healthy women (19-24 years old). The magnitude and the direction of instantaneous QRS vectors in the 10th to the 70th ms and in QRS max were constructed from the Frank lead ECG. The significant alterations of the direction (angle) were found in the 30th ms and QRS max at HXV and in the 60th ms at HV. A significant decrease in the magnitude of instantaneous vectors was found in the 10th to 50th ms after 6 min of HXV, in the 30th to 50th ms at 3 min of HXV, in the 40th to 50th ms at HV. These alterations were the most marked in the horizontal plane. We suggest that the alterations of the instantaneous QRS vectors were caused by the influence of the autonomic nervous system or humoral agents, but not by heart position, Brody's effect or lung hyperinflation. PMID- 1299325 TI - Human neutrophil mobilization during open heart surgery. AB - Phagocyte released reactive oxygen species are often discussed in connection with ischemic and reperfusion injuries to the myocardium. The kinetics of the accumulation and oxidative burst of human blood phagocytes was studied by chemiluminescence during open heart surgery in the myocardium of human patients. Direct evidence is presented for an accumulation of neutrophils along with their markedly increased metabolic activity (oxygen radical formation), especially following the reperfusion of the ischemic myocardium. Leukocyte numbers and activity remained significantly elevated even in the venous blood obtained 24 h after the operation. PMID- 1299326 TI - Some properties of linear relaxation in unfused tetanus of human muscle. AB - The linear relaxation (LR) was studied in isometric unfused tetanus (UT) of the human flexor digitorum sublimis muscle. With a decrease of the force level, the shoulder on the relaxation curve, as measured from the last stimulus, shifted to the right. The length of the linear portion itself weakly depended on activation level. When steady force changed from 100 to 40-50% of the maximum, the slope of LR decreased only by 15 +/- 4%. At smaller force levels the slope began to increase. LR can probably also be hidden in the twitch. With increased tetanus duration, LR becomes longer and slower at all force levels. LR was markedly diminished in contraction on the steep part of the exponential relaxation after a smooth tetanus. Its full recovery needed a train of 4-5 pulses (near 1 s) at the new stationary level. The form of the response to the additional pulse given during relaxation remained approximately constant during the most of LR portion and differed markedly before and after it. LR did not have direct relation to fatigue: in the first UT LR was always slower and longer than in subsequent ones. PMID- 1299327 TI - Influence of ketamine on the spontaneous motility of chick embryos and its development. AB - The effects of acute and chronic application of ketamine on the resting spontaneous motility, its development and reactivity was studied in chick embryos of white Leghorns. 1. Acute application of ketamine (Narcamon) in a dose of 12.5 mg/kg e.w. partially depressed spontaneous motility as early as in 11-day old chick embryos. From day 15 of incubation ketamine very effectively blocked spontaneous motility. 2. Ketamine was fully ineffective in spinal preparations (decapitation on day 2 of incubation) of 11- and 13-day-old embryos. It was not until day 15 evoked that it depressed motility as in normal embryos. 3. Chronic continuous supply of ketamine (average dose 6.34 +/- 0.72 mg/kg e.w./24 h) from day 4 of incubation till day 8, 12, or 16 of incubation reduced the developmental decrease of spontaneous motility by 23.1-6.0% as compared to the controls. This effect was already observed after the first 4 days of chronic application of ketamine. 4. Chronic application of ketamine significantly diminished the strychnine activation and GABA-mediated depression of spontaneous motility. The depressive effect of the acute application of ketamine itself was hardly affected. The results have shown that ketamine interferes with the development of the endogenous rhythm of intrinsic activity and with the development of reactivity of the generator of embryonic spontaneous motility. PMID- 1299328 TI - Antimetrazol action of two potential anticonvulsants, CM 40907 and SR 41378, in immature rats. AB - The action of two potential anticonvulsants, CM 40907 (10-50 mg/kg i.p.) and SR 41378 (1.25-20 mg/kg i.p.) against metrazol-induced seizures was studied in rats 7, 12, 18 and 25 days old. Two types of motor seizures--minimal, clonic and major, generalized tonic-clonic--were elicited by a 100-mg/kg dose of metrazol (s.c.) and their incidence and latency were evaluated. The severity of seizures was expressed as a score on a 5-point scale. Dimethylsulfoxide, an organic solvent, exhibited anticonvulsant action only in doses far exceeding those used for dissolving the two anticonvulsants. Both drugs suppressed minimal as well as major seizures in all age groups studied in a dose-dependent manner, SR 41378 being approximately four times more potent than CM 40907. The latencies could be measured only in animals given low doses of anticonvulsants. CM 40907 did not change the latencies whereas SR 41378 prolonged them. The severity of seizures was decreased again in a dose-dependent manner. There were only minor changes in the efficacy of CM 40907 among the four age groups. On the contrary, SR 41378 exhibited an extreme efficacy in 7-day-old rat pups, where even the 1.25 mg/kg dose significantly decreased the incidence and severity of seizures. The efficacy in the remaining three age groups was approximately at the same level as in adult rats. PMID- 1299329 TI - Are embryonal neurones used for transplantation "sufficiently immature"? AB - Live neuronal suspensions, prepared from the hippocampal region of donors aged 20 embryonal days, were observed in the Nomarski Differential Interference Contrast. Many neurones displayed profiles, resembling dendrites or axons and both principal hippocampal neurones (pyramidal and granular cells) were identified. For transplantation studies, donors of a younger embryonal age are thus recommended. PMID- 1299330 TI - The influence of glucose and saccharose on haemolytic action of HgCl2 in relation to the ionic strength of the incubating medium. AB - The haemolytic action of HgCl2 (0, 15 mmol.l-1) was studied in relation to the ionic strength and concentration of glucose and saccharose in incubating medium. Blood from 94 donors, aged 19-46 years were used in our experiments. In relation to the ionic strength the haemolytic action was characteristic with two maxima of haemolysis. The first at low ionic strength and second one at the high. Both maxima in solutions containing saccharose were significantly diminished in glucose. These facts show a negative influence of saccharose on the haemorheological properties of the erythrocyte membrane. PMID- 1299332 TI - Effect of isoproterenol on 85Sr accumulation in the myocardium of the rat during postnatal ontogeny. AB - The aim of this study was to establish whether administration of toxic doses of isoproterenol (IPRO) increases the accumulation of strontium--a homologue element of calcium--in the rat heart during postnatal development. It has been shown that in 14-day-old animals 85Sr uptake was not increased; starting from the 30th day of postnatal life this parameter increases significantly up to adulthood. PMID- 1299331 TI - The influence of prolonged cimetidine administration on serum gastrin levels and gastric acid secretion in rats. AB - The correlation between serum gastrin levels and gastric acid secretion during 4 weeks of cimetidine administration (once daily) was investigated. Serum gastrin levels and gastric acid secretion were estimated on the 7th, 14th, 21st and 28th day after cimetidine administration (25 mg.kg-1, intragastrically). At the mentioned time intervals gastric acid secretion stimulated by histamine and pentagastrin was also studied. It was found that on the 14th and 21st day after cimetidine administration serum gastrin levels were significantly elevated. Basal gastric acid secretion after cimetidine administration was significantly decreased at all the observed time intervals. Histamine-stimulated gastric acid secretion was increased on the 14th, 21st and 28th day after cimetidine administration. Hypoacidity was not followed at all time intervals by hypergastrinaemia (only on day 14 and 21 after cimetidine). PMID- 1299333 TI - Influence of phenytoin and valproate on thalamocortical evoked potentials and their paired-pulse potentiation. AB - The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm. PMID- 1299334 TI - [Antiendomysium antibodies in the diagnosis of celiac disease in the adult]. AB - The identification of anti-endomysial antibodies in the serum of coeliac patients has provided a useful diagnostic tool to be used together with biopsy. In this study the presence of these antibodies was evaluated in a population of adult coeliac patients. 92.86% sensitivity and 100% specificity were obtained together with 98.68% diagnostic accuracy. The antibody titer tends to diminish progressively and become negative in patients who adhere strictly to their diet. Anti-endomysial antibodies may therefore be used at both the screening stage as well as during follow-up and they allow an objective assessment of diet compliance to be made. PMID- 1299335 TI - [Hepatic abscess]. AB - The Authors review the medical records of 9 patients with liver abscess over a 15 year period from 1975 to 1989. They report on 5 pyogenic abscess, 3 amebic abscess and one case of tuberculosis of the liver. The most common initial diagnosis was fever of unknown origin, abdominal pain and hepatomegaly. The treatment consisted of 6 percutaneous transhepatic drainage, 2 open surgical drainage, and one explorative laparotomy (tbc infection). The Authors had no mortality and recommend the percutaneous transhepatic drainage as first-choice treatment. PMID- 1299336 TI - [Pain in chronic pancreatitis: recent pathogenetic findings]. AB - Pain is the major symptom in chronic pancreatitis. Its intensity frequently necessitates partial or complete pancreatectomy. The mechanisms of pain are not yet fully understood and, thereby, the therapeutic management is still controversial. Possible causes of pain include outflow obstruction with increased ductal and parenchymal pressure within the pancreas, and inflammatory involvement of intrapancreatic nerve fibres. Possible extrapancreatic causes are common bile duct and duodenal stenosis. The first theory has recently been substantiated by the demonstration of a definite relationship between intrapancreatic pressure, as measured intraoperatively, and intensity of pain. Infiltration of inflammatory cells around the nerves together with an increase in the number of nerve fibres in the fibrotic pancreatic tissue has been proposed as a possible cause of pain in chronic pancreatitis. Moreover, immunohistological studies have shown that the amount of neurotransmitters, such as substance P, is increased in afferent pancreatic nerves. Stenosis of the common bile duct and duodenum has been reported to be associated with severe abdominal pain. Common bile duct and duodenal stenosis in chronic pancreatitis may be caused by extension of fibrosis and active inflammation of the pancreas within the wall of duodenum and bile duct. This article updates the different pathogenetic mechanisms in pancreatic pain and the current therapeutic possibilities with their advantages and shortcomings. PMID- 1299337 TI - [S-adenosyl-L-methionine (SAMe) and its use in hepatology]. AB - S-adenosyl-L-methionine (SAMe), a molecule naturally present in several body tissues and fluids, is produced, by SAMe synthetase, from ATP and methionine. SAMe has a fundamental role, as methyl group donor, in transmethylation reactions in which the synthesis of membrane phospholipids (especially phosphatidylcholine) is mandatory for the maintenance of membrane fluidity. Another metabolic pathway involving SAMe, transsulphuration, is initiated with the release of -CH3 from the molecule and the formation of S-Adenosyl-homocysteine and then homocysteine and cysteine, a precursor of glutathione the main cellular antioxidant, responsible of detoxification of various compounds and xenobiotics. At last SAMe is implicated in aminopropylation process for the polyamine synthesis. The development of stable double salt of p-toluene sulphonic acid and sulphuric acid of SAMe enables the clinical use of the drug, as a therapeutical agent, for the treatment of a number of liver dysfunctions. In various animal and human models, including controlled trials, it has been demonstrated that SAMe can ameliorate some biochemical parameters and pruritus in cholestasis induced by a range of compounds (i.e. oestrogens, lithocolate, etc) and in intrahepatic cholestasis superimposed to chronic liver disease. Concerning alcohol toxicity, SAMe prevents, in ethanol fed baboons, depletion of glutathione levels, normalizes the mitochondrial enzymes and improves the histological hepatic lesions. In human healthy volunteers it has been recently demonstrated that SAMe, after ethanol ingestion, significantly lowers plasma concentration of ethanol and acetaldehyde as well. Finally, SAMe has been proposed, instead of N-acetylcysteine, as precursor of glutathione, in patients who present late after ingestion of an overdose of paracetamol. PMID- 1299338 TI - [Possibilities and limitations of nutritional support in Crohn disease]. AB - Crohn's disease involves a great risk of malnutrition. Malabsorption, bacterial contamination, frequent abdominal surgery, meal-related pain, protein loss through the damaged mucosa contribute to creating nutritional problems. Malnutrition can worsen the outcome, both in medical and surgical patients, and deteriorate an often already altered immune response. Weight loss, low levels of blood protein, electrolytes, micronutrients and vitamins are usually related to the extension of the mucosal damage. Nutritional assessment can be difficult due to oedema and bleeding, who interfere with both clinical and laboratory evaluation. The exact amount of nitrogen, lipids, minerals stool loss can be useful. It is widely accepted the use of nutritional support in Crohn's disease, but many Authors do not agree concerning the route (enteral or parenteral) and the kind of nutrient to be used. Still controversial is the role of nutrition: just support or real therapy? Most recent hypothesis concerning the pathogenesis of Crohn's disease indicate food and/or bacterial antigens as involved in determining the pathology. The "bowel rest", considered for many years as a fasting period necessarily supported by parenteral nutrition, can also be obtained by the temporarily reduction or stop in presenting those antigens to the bowel mucosa. This new concept can be achieved not only by parenteral nutrition, but with an enteral elemental diet as well. The elemental diet contains all nutrients in the simplest way and thus succeeds in lowering or eliminating the antigenic power. The reported results seem to indicate an equivalence of enteral and parenteral nutrition; anyway enteral is advisable when feasible, being more physiological and less expensive and involving a lower risk of serious complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299339 TI - [The works of Prof. S. E. Manoilov]. AB - A biographic essay of professor S. E. Manoilov scientific works is given. The course of life of this scientist is of great interest as an example of fruitful creation under difficult conditions of our present-day reality. PMID- 1299340 TI - [The inhibition of translation in Bacillus subtilis via the repression by the secreted enzyme of its synthesis]. AB - It has been shown that inhibition of Bacillus subtilis alpha-amylase formation by the level of the active enzyme in the cultural medium leads to the decrease of translation accompanied by reduction of level of [14C] valin transport into the cells. PMID- 1299341 TI - [Lactase polymorphism in representatives of different ethnic-territorial groups]. AB - Lactase polymorphism was studied in the native population of West Siberia and also in Buryatia. LAC*R frequency observed is-Khants- 0.8367, Mansi - 0.8660, Nenets - 0.8944, Buryats - 0.6883. The data obtained are considered to be the result of natural selection under traditional historical economical-cultural environment of the ethnic groups in question. PMID- 1299343 TI - [An evaluation of the genotoxicity of nonionogenic surface-active substances]. AB - The mutagenic activity of 16 industrial nonionic surfactant samples has been investigated in Ames-test without metabolic activation and with the use of mouse liver microsomal fraction in vitro. The genotoxical estimation of their possible biodegradation products is given. The mutagenicity of a number of high molecular polyethylene glycoles related to nonionic surfactants is shown. PMID- 1299342 TI - [The genetic-demographic approach in anthropological research. X. The dynamics of the sex-age structure of Khakass populations]. AB - Social-economic remakings in Siberia are reflected in the economy of a rural inhabitant and the sex-age structure of the Khakass populations. The age average of the population increased from 26.7 years in 1954 up to 31.2 years in 1980. It has been established that the effectively reproductive size of a population (Ne) which takes into account its historical extent serves as a satisfactory estimate of the veritable (not single, instantaneous) size of a population. PMID- 1299344 TI - Human B cell differentiation induced by microbial superantigens: unselected peripheral blood lymphocytes secrete polyclonal immunoglobulin in response to Mycoplasma arthritidis mitogen. AB - Microbial superantigens (SA) activate a significant portion of the T cell repertoire based on their dual avidity for MHC class II antigens and T cell receptor (TCR) epitopes common to products of one or several TCR beta chain variable gene families. While SA that induce massive T cell proliferation and cytokine secretion have been implicated in clinical syndromes characterized by shock and generalized immunosuppression, SA activation of a more restricted T cell response may also have significant, perhaps immunostimulatory, effects on the immune system. To investigate this issue, we measured 3H-thymidine incorporation and polyclonal IgM and IgG secretion by normal human peripheral blood mononuclear cells (PBMC) cultured with a panel of microbial SA, including the Staphylococcus aureus-derived SA, SEA, SEB, SEC-1, SEC-2, SEC-3, SEE, TSST-1, and the Mycoplasma arthritidis-derived SA, MAM. The S. aureus-derived SA induce vigorous proliferation by PBMC, while optimal MAM-induced proliferation is significantly lower in magnitude. In all 12 subjects tested, mitogenic concentrations of MAM reproducibly stimulate unselected PBMC to secrete polyclonal IgM and IgG. In contrast, the S. aureus-derived SA induce Ig production only in cultures containing isolated B cell populations and either very low numbers of untreated autologous T cells, larger numbers of X-irradiated autologous T cells, or very low concentrations of the SA. No difference in the activation of helper (CD4) versus suppressor/cytotoxic (CD8) T cells by MAM and the S. aureus-derived SA was noted. Taken together, these data suggest that MAM's capacity to induce B cell differentiation correlates with its induction of a relatively weak proliferative response by unselected human T cells. MAM-like SA, when encountered in vivo, may result in a significant perturbation of the human immune system and potentially contribute to clinical syndromes characterized by immunostimulation and hypergammaglobulinemia. PMID- 1299345 TI - Circulating antibodies to DNA-related antigens in patients with autoimmune thyroid disorders. AB - A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299347 TI - Comparison of the N- and O-linked glycopeptides of lymph node cells from C57 BL/6 lpr/lpr and C57 BL/6 mice. AB - We have tested the hypothesis that some phenotypic characteristics of the lymphocytes from mice with lymphoproliferative disease (lpr) could be explained by abnormal glycosylation of membrane proteins. Lymph node cells from normal C57 BL/6 and from C57 BL/lpr mice were labelled with tritiated sugars. Membrane proteins were released with trypsin, then with pronase. After complete pronase digestion, glycopeptides were first separated on Bio Gel P-6 and then on Con A Sepharose. Fractions not binding to Con A (Con A negative) were also separated on Lens culinaris agglutinin-Sepharose. Marked differences between normal and lpr cells were noticed. First, there were more glucosamine-labelled peptides with very high molecular weight (eluting fast on Bio Gel P-6) on lpr cells than on normal lymphocytes. Second, the proportion of mannose-labelled peptides binding to Con A was smaller in the lpr cells. Third, among the Con A negative peptides, the proportion binding to Lens culinaris agglutinin was higher in lpr cells. Thus, lpr cells seem to carry more alpha 1-6 fucosylated chains and larger size carbohydrates. These alterations were also confirmed by gel electrophoresis of lectin-selected iodinated cell surface antigens and seem to be restricted to a very limited number of peptides. Thus, there may be primary changes in glycosylation in lpr cells. Alternatively, the glycosylation pattern of lpr cells may be characteristic for a subpopulation of T-lymphocytes that is expanded in this disease, or for a certain stage of activation. A large proportion of Con A negative, Lens culinaris-positive peptides is a rather unusual feature in murine cells and requires further investigation. PMID- 1299346 TI - Inhibition of human T lymphocyte proliferation and cytokine production by 1,25 dihydroxyvitamin D3. Differential effects on CD45RA+ and CD45R0+ cells. AB - 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), the biologically active form of vitamin D3, has been shown to modulate lymphocyte functions in vitro. These effects are exerted through binding to specific receptors that are expressed in activated, but not in resting lymphocytes. 1,25-(OH)2 D3 inhibits lymphocyte proliferation, immunoglobulin production and the release of cytokines including interleukin-2 (IL-2) and interferon gamma (IFN gamma) by mitogen driven blood mononuclear cells (MNC). A distinction between CD45RA+ and CD45R0+ subsets of T cells has, however, proven extremely relevant in terms of immunoactivation and immunopathology. The present study was undertaken to evaluate effects of 1,25-(OH)2 D3 on proliferation and cytokine production by purified CD45RA+ and CD45R0+ T cells. 1,25-(OH)2 D3 caused a dose- and time-dependent reduction in phytohemagglutinin (PHA) and poke-weed mitogen (PWM)-driven proliferation of purified CD45R0+ T cells. In contrast, proliferation of the CD45RA+ subset was unaffected by this treatment. Comparable levels of lymphotoxin (LT), IFN gamma and IL-2 were obtained in cultures of both subsets. 1,25-(OH)2 D3 reduced these levels, but the suppressive effect of the hormone was delayed in cultures of CD45RA+ T cells. The results suggest that the CD45R0+ subset is relatively more sensitive than CD45RA+ subset to the inhibitory effects of 1,25-(OH)2 D3. This finding may be of pharmacological interest, because the CD45R0+ subset plays a key role in immune activation and because these cells have been associated with the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. PMID- 1299348 TI - Autoantibodies to endogenous growth hormone in short children (the Wessex Growth Study). AB - Small stature is associated with low growth hormone secretion, but in most cases the reason is unknown. The commonest cause of hormone insufficiency is autoimmunity, and autoantibodies to hormones are often found where there is autoimmune disease of the corresponding gland. Displaceable growth hormone binding by the sera of 125 short (< 3rd centile) but otherwise normal school entrants was significantly higher (P < 0.05) than by the sera of 100 age-matched children of normal height (10th-90th centile), and binding in 21 (17%) of the small children exceeded the upper limit of 95% of the normal population. Furthermore, urinary growth hormone excretion was significantly lower in the small children (total overnight output 0.6-1.7 ng) compared with controls (1.5 3.7 ng) (P < 0.05) even when corrected for body surface area. Thus, growth hormone binding and growth hormone excretion discriminated between two groups of children selected only on the basis of height. The assay used for growth hormone binding was specific for IgG, suggesting that the binding factor was antibody. Autoimmunity merits further investigation as a basis for poor growth. PMID- 1299349 TI - Differential effects of immunisation with mycobacterial 65 kD heat shock protein on two models of autoimmunity. AB - The effects of preimmunisation with the 65 kD mycobacterial heat shock protein (hsp65) on 2 murine models of autoimmunity were compared. Experimental autoimmune haemolytic anaemia (AIHA) can be provoked in mice by repeated injection with rat red blood cells (RBC). In this model, preimmunisation with hsp65 10 days before induction of disease resulted in a partial, but significant, reduction in RBC bound autoantibody levels measured by Coombs' test. However, preimmunisation with human IgG (hIgG) was associated with a similar suppressive effect. Administration of neither hsp65 nor hIgG affected the direct or indirect anti-rat agglutinin titres of mice subsequently injected with rat RBC. Injection of hsp65 or hIgG prior to induction of AIHA elicited the production of IgG antibodies against the respective immunogen, as judged by enzyme-linked immunosorbent assays. In contrast to the results in experimental AIHA, pristane-induced arthritis (PIA) was effectively prevented by preimmunisation with hsp65, but not with hIgG. It is considered that, whilst hsp65 injection may slightly reduce subsequent anti-RBC autoantibody production in AIHA by antigenic competition, such a mechanism cannot account for the substantial protection against PIA afforded by hsp65 preimmunisation. We suggest that the high, sustained production of anti-hsp65 antibodies observed in mice given hsp65 and pristane may play a role in specifically suppressing arthritogenic immune responses in PIA. PMID- 1299350 TI - HLA-DQ associations with autoimmune disease. PMID- 1299351 TI - Memory abnormalities in myasthenia gravis: possible fatigue of central nervous system cholinergic circuits. PMID- 1299352 TI - Significance of anti-eye muscle antibody in patients with thyroid-associated ophthalmopathy by quantitative western blot. AB - To investigate the prevalence of antibody against rat eye muscle membrane antigen, as determined from SDS-polyacrylamide gel electrophoresis and western blotting, in sera from patients with thyroid-associated ophthalmopathy (TAO), we quantitatively analyzed the binding activity with a rat eye muscle membrane 64 kDa protein using chromato-scanner. Eye muscle antibody activity was expressed as ratio of density of the 64 kDa band to that at 66 kDa found with all normal sera and phosphate buffered saline. The mean (+/- SD) eye muscle antibody activity was 2.7 +/- 2.7 in TAO (P < 0.01 v.s. normal), 1.5 +/- 1.7 in Graves' disease without evident eye disease, 1.6 +/- 2.5 in Hashimoto's thyroiditis and 0.45 +/- 0.26 in normal subjects. A positive band at 64 kDa was found in 71% of patients with TAO, 36% of those of Graves' disease without evident eye disease and in 35% of patients with Hashimoto's thyroiditis without eye disease. The prevalence of this antibody activity tended to correlate to the severity of ophthalmopathy. Furthermore, the level of eye muscle antibody activity decreased in parallel with the improvement of eye signs in two patients. Sera reactive with rat eye muscle membrane 64 kDa protein reacted also with a human eye muscle membrane 64 kDa protein but not with human thyroid, liver, spleen or pancreas membrane preparations. In conclusion, antibody to rat eye muscle membrane 64 kDa protein is present in TAO and may be a useful clinical marker of ophthalmopathy. PMID- 1299353 TI - Interactions of FGFs with target cells. AB - Growth factors play a key role in cellular communication, a necessary step for the development of pluricellular organisms. The fibroblast growth factors (FGF) are among these polypeptides and have seven known members: FGF 1 to FGF 7 which are also known as acidic FGF, basic FGF, translation products of oncogenes hst, int 2, FGF 5, FGF 6 and FGF 7 or keratinocyte growth factor (KGF) respectively [1]. The best known and the most abundant in normal adult tissues are acidic and basic FGFs, or FGF 1 and 2 respectively, which have been subjected to extensive studies both in vitro and in vivo. These two factors have almost ubiquitous distribution and a wide spectrum of biological activity including action on cellular proliferation and differentiation, as well as neurotrophic and angiogenic properties [1]. These different activities are induced by triggering specific receptors present at the surface of the target cell. Following this interaction, the FGF-receptor complexes are internalized and activate intracellular pathways. An important effort of investigations has been produced to characterize these receptors and intracellular pathways. It is the purpose of this review to present this work which will focus on FGFs 1 and 2. The existence of two classes of interactions has been reported as early as 1987 [52, 53, 54] suggesting the presence of high and low affinity receptors for FGFs. PMID- 1299354 TI - Bibliographic update: insulin-like growth factor. PMID- 1299355 TI - The causal analysis of development in the past half century: a personal history. PMID- 1299356 TI - Epithelial differentiation and intercellular junction formation in the mouse early embryo. AB - Trophectoderm differentiation during blastocyst formation provides a model for investigating how an epithelium develops in vivo. This paper briefly reviews our current understanding of the stages of differentiation and possible control mechanisms. The maturation of structural intercellular junctions is considered in more detail. Tight junction formation, essential for blastocoele cavitation and vectorial transport activity, begins at compaction (8-cell stage) and appears complete before fluid accumulation begins a day later (approx 32-cell stage). During this period, initial focal junction sites gradually extend laterally to become zonular and acquire the peripheral tight junction proteins ZO-1 and cingulin. Our studies indicate that junction components assemble in a temporal sequence with ZO-1 assembly preceding that of cingulin, suggesting that the junction forms progressively and in the 'membrane to cytoplasm' direction. The protein expression characteristics of ZO-1 and cingulin support this model. In contrast to ZO-1, cingulin expression is also detectable during oogenesis where the protein is localised in the cytocortex and in adjacent cumulus cells. However, maternal cingulin is metabolically unstable and does not appear to contribute to later tight junction formation in trophectoderm. Cell-cell interactions are important regulators of the level of synthesis and state of assembly of tight junction proteins, and also control the tissue-specificity of expression. In contrast to the progressive nature of tight junction formation, nascent desmosomes (formed from cavitation) appear mature in terms of their substructure and composition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299357 TI - Mesoderm-inducing factors and the control of gastrulation. AB - One of the reasons that we know so little about the control of vertebrate gastrulation is that there are very few systems available in which the process can be studied in vitro. In this paper, we suggest that one suitable system might be provided by the use of mesoderm-inducing factors. In amphibian embryos such as Xenopus laevis, gastrulation is driven by cells of the mesoderm, and the mesoderm itself arises through an inductive interaction in which cells of the vegetal hemisphere of the embryo emit a signal which acts on overlying equatorial cells. Several factors have recently been discovered that modify the pattern of mesodermal differentiation or induce mesoderm from presumptive ectoderm. Some of these mesoderm-inducing factors will also elicit gastrulation movements, which provides a powerful model system for the study of gastrulation, because a population of cells that would not normally undertake the process can be induced to do so. In this paper, we use mesoderm-inducing factors to attempt to answer four questions. How do cells know when to gastrulate? How do cells know what kind of gastrulation movement to undertake? What is the cellular basis of gastrulation? What is the molecular basis of gastrulation? PMID- 1299358 TI - Muscle gene activation in Xenopus requires intercellular communication during gastrula as well as blastula stages. AB - In Xenopus an early morphological marker of mesodermal induction is the elongation of the mesoderm at the early gastrula stage (Symes and Smith, 1987). We show here that the elongation of equatorial (marginal) tissue is dependent on protein synthesis in a mid blastula, but has become independent of it by the late blastula stage. In animal caps induced to become mesoderm, the time when protein synthesis is required for subsequent elongation immediately follows the time of induction, and is not related to developmental stage. For elongation, intercellular communication during the blastula stage is of primary importance. Current experiments involving cell transplantation indicate a need for further cell:cell interactions during gastrulation, and therefore after the vegetal animal induction during blastula stages. These secondary cell interactions are believed to take place among cells that have already received a vegetal induction, and may facilitate some of the later intracellular events known to accompany muscle gene activation. PMID- 1299359 TI - Specification of the body plan during Xenopus gastrulation: dorsoventral and anteroposterior patterning of the mesoderm. AB - Although the mesoderm itself is induced at the blastula stage, its subdivision mainly occurs in response to further inductive signals during gastrulation. In the late blastula, most of the mesoderm has a ventral-type commitment except for the small organizer region which extends about 30 degrees on each side of the dorsal midline. During gastrulation, dorsal convergence movements bring the cells of the lateroventral marginal zone up near the dorsal midline and into the range of the dorsalizing signal emitted by the organizer. This dorsalizing signal operates throughout gastrulation, can cross a Nuclepore membrane, and is not mimicked by lithium, FGFs or activin. Anteroposterior specification also takes place during gastrulation and is probably controlled by a dominant region at the posterior end of the forming axis. We have studied the expression patterns in Xenopus of three members of the FGF family: bFGF, int-2 and a newly discovered species, eFGF. These all have mesoderm inducing activity on isolated animal caps, but are likely also to be involved with the later interactions. RNAase protections and in situ hybridizations show that the int-2 and eFGF mRNAs are concentrated at the posterior end, while bFGF is expressed as a posterior to anterior gradient from tailbud to head. Studies of embryos in which bFGF is overexpressed from synthetic mRNA show that biological activity is far greater when a functional signal sequence is provided. This suggests that int-2 and eFGF, which possess signal sequences, are better candidates for inducing factors in vivo than is bFGF. PMID- 1299360 TI - Evolution of developmental decisions and morphogenesis: the view from two camps. AB - Modern developmental biology largely ignores evolution and instead focuses on use of standard model organisms to reveal general mechanisms of development. Evolutionary biologists more widely hold developmental biology to be of major consequence in providing potential insights into evolution. Evolutionary insights can enlighten our views of developmental mechanisms as much as developmental data offer clearer views of mechanisms which underlie evolutionary change. However, insights have been limited by the long-term disengagement of the two fields dating to the rise of experimental embryology in the 1890s. Molecular genetics now provides a powerful tool to probe both gene function and evolutionary relationships, and a greater connection has become possible. The expansion of experimental organisms beyond the standard model animals used in most studies of development allows us to ask deeper questions about the interaction of development and evolution. This paper presents an analysis of the complementary uses of the resulting data in the two fields as they grope for accommodation. Analysis of the radical changes in early development seen in closely related sea urchins with alternate modes of development illustrate the complementarity of developmental and evolutionary data. These studies show that what have been thought to be constrained mechanisms of axial determination, cell lineage patterning, and gastrulation in fact evolve readily and provide the means for the rapid evolution of development. PMID- 1299361 TI - Relationships between mesoderm induction and the embryonic axes in chick and frog embryos. AB - The hypoblast is generally thought to be responsible for inducing the mesoderm in the chick embryo because the primitive streak, and subsequently the embryonic axis, form according to the orientation of the hypoblast. However, some cells become specified as embryonic mesoderm very late in development, towards the end of the gastrulation period and long after the hypoblast has left the embryonic region. We argue that induction of embryonic mesoderm and of the embryonic axis are different and separable events, both in amniotes and in amphibians. We also consider the relationships between the dorsoventral and anteroposterior axes in both groups of vertebrates. PMID- 1299363 TI - Dorsoventral development of the Drosophila embryo is controlled by a cascade of transcriptional regulators. AB - Maternal genes involved in dorsoventral (D/V) patterning of the Drosophila embryo interact to establish a stable nuclear concentration gradient of the Dorsal protein which acts as the morphogen along this axis. This protein belongs to the rel proto-oncogene and NF-KB transcriptional factor family and acts by controlling zygotic gene expression. In the ventral part of the embryo, dorsal specifically activates transcription of the gene twist and ventrally and laterally dorsal represses the expression of zerknullt, a gene involved in the formation of dorsal derivatives. The extent of dorsal action is closely related to the affinity and the number of dorsal response elements present in these zygotic gene promoters. twist is one of the first zygotic genes necessary for mesoderm formation. It codes for a 'b-HLH' DNA-binding protein which can dimerize and bind to DNA in vitro and to polytene chromosomes in vivo. In addition, in cultured cells twist has been shown to be a transcriptional activator. Thus, the first events of embryonic development along the D/V axis are controlled at the transcriptional level. PMID- 1299362 TI - Brachyury--a gene affecting mouse gastrulation and early organogenesis. AB - Mouse embryos that are homozygous for the Brachyury (T) deletion die at mid gestation. They have prominent defects in the notochord, the allantois and the primitive streak. Expression of the T gene commences at the onset of gastrulation and is restricted to the primitive streak, mesoderm emerging from the streak, the head process and the notochord. Genetic evidence has suggested that there may be an increasing demand for T gene function along the rostrocaudal axis. Experiments reported here indicate that this may not be the case. Instead, the gradient in severity of the T defect may be caused by defective mesoderm cell movements, which result in a progressive accumulation of mesoderm cells near the primitive streak. Embryonic stem (ES) cells which are homozygous for the T deletion have been isolated and their differentiation in vitro and in vivo compared with that of heterozygous and wild-type ES cell lines. In +/+<-->T/T ES cell chimeras the Brachyury phenotype is not rescued by the presence of wild-type cells and high level chimeras show most of the features characteristic of intact T/T mutants. A few offspring from blastocysts injected with T/T ES cells have been born, several of which had greatly reduced or abnormal tails. However, little or no ES cell contribution was detectable in these animals, either as coat colour pigmentation or by isozyme analysis. Inspection of potential +/+<-->T/T ES cell chimeras on the 11th or 12th day of gestation, stages later than that at which intact T/T mutants die, revealed the presence of chimeras with caudal defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299364 TI - Retinoic acid and the late phase of neural induction. AB - Regional neural gene expression in Xenopus is the result of a number of processes that continue well beyond the end of gastrulation. By considering two of the basic features of neural induction, the duration of contact between mesoderm and ectoderm and the timing of neural competence, it has been possible to distinguish two phases in neural tissue formation. The late phase includes the period following gastrulation. A factor in determining regional neural gene expression is the difference in inducing ability of the mesoderm that develops during gastrulation along the anterior-posterior axis. The resulting ability to express regional neural genes is subsequently refined during the late phase by a signal that progresses from the posterior part of the embryo. Using a dorsal explant system, it is shown that this progressive signal can be mimicked by the addition of retinoic acid (RA). However, the observation that regions along the anterior posterior axis respond in different ways to the addition of RA suggests that additional factors are also important in defining regional neural gene expression. One possibility is that the expression of retinoic acid receptors along the axis may demarcate regions that respond to RA in particular ways. PMID- 1299365 TI - Mechanisms of early Drosophila mesoderm formation. AB - Several morphogenetic processes occur simultaneously during Drosophila gastrulation, including ventral furrow invagination to form the mesoderm, anterior and posterior midgut invagination to create the endoderm, and germ band extension. Mutations changing the behaviour of different parts of the embryo can be used to test the roles of different cell populations in gastrulation. Posterior midgut morphogenesis and germ band extension are partly independent, and neither depends on mesoderm formation, nor mesoderm formation on them. The invagination of the ventral furrow is caused by forces from within the prospective mesoderm (i.e. the invaginating cells) without any necessary contribution from other parts of the embryo. The events that lead to the cell shape changes mediating ventral furrow formation require the transcription of zygotic genes under the control of twist and snail. Such genes can be isolated by molecular and genetic screens. PMID- 1299366 TI - Pattern formation during gastrulation in the sea urchin embryo. AB - The sea urchin embryo follows a relatively simple cell behavioral sequence in its gastrulation movements. To form the mesoderm, primary mesenchyme cells ingress from the vegetal plate and then migrate along the basal lamina lining the blastocoel. The presumptive secondary mesenchyme and endoderm then invaginate from the vegetal pole of the embryo. The archenteron elongates and extends across the blastocoel until the tip of the archenteron touches and attaches to the opposite side of the blastocoel. Secondary mesenchyme cells, originally at the tip of the archenteron, differentiate to form a variety of structures including coelomic pouches, esophageal muscles, pigment cells and other cell types. After migration of the secondary mesenchyme cells from their original position at the tip of the archenteron, the endoderm fuses with an invagination of the ventral ectoderm (the stomodaem), to form the mouth and complete the process of gastrulation. A larval skeleton is made by primary mesenchyme cells during the time of archenteron and mouth formation. A number of experiments have established that these morphogenetic movements involve a number of cell autonomous behaviors plus a series of cell interactions that provide spatial, temporal and scalar information to cells of the mesoderm and endoderm. The cell autonomous behaviors can be demonstrated by the ability of micromeres or endoderm to perform their morphogenetic functions if either is isolated and grown in culture. The requirement for cell interactions has been demonstrated by manipulative experiments where it has been shown that axial information, temporal information, spatial information and scalar information is obtained by mesoderm and endoderm from other embryonic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299367 TI - Cell interactions and mesodermal cell fates in the sea urchin embryo. AB - Cell interactions during gastrulation play a key role in the determination of mesodermal cell fates in the sea urchin embryo. An interaction between primary and secondary mesenchyme cells (PMCs and SMCs, respectively), the two principal populations of mesodermal cells, regulates the expression of SMC fates. PMCs are committed early in cleavage to express a skeletogenic phenotype. During gastrulation, they transmit a signal that suppresses the skeletogenic potential of a subpopulation of SMCs and directs these cells into an alternative developmental pathway. This review summarizes present information concerning the cellular basis of the PMC-SMC interaction, as analyzed by cell transplantation and ablation experiments, fluorescent cell labeling methods and the use of cell type-specific molecular markers. The nature and stability of SMC fate switching, the timing of the PMC-SMC interaction and its quantitative characteristics, and the lineage, numbers and normal fate of the population of skeletogenic SMCs are discussed. Evidence is presented indicating that PMCs and SMCs come into direct filopodial contact during the late gastrula stage, when the signal is transmitted. Finally, evolutionary questions raised by these studies are briefly addressed. PMID- 1299368 TI - A gastrulation center in the ascidian egg. AB - A gastrulation center is described in ascidian eggs. Extensive cytoplasmic rearrangements occur in ascidian eggs between fertilization and first cleavage. During ooplasmic segregation, a specific cytoskeletal domain (the myoplasm) is translocated first to the vegetal pole (VP) and then to the posterior region of the zygote. A few hours later, gastrulation is initiated by invagination of endoderm cells in the VP region of the 110-cell embryo. After the completion of gastrulation, the embryonic axis is formed, which includes induction of the nervous system, morphogenesis of the larval tail and differentiation of tail muscle cells. Microsurgical deletion or ultraviolet (UV) irradiation of the VP region during the first phase of myoplasmic segregation prevents gastrulation, nervous system induction and tail formation, without affecting muscle cell differentiation. Similar manipulations of unfertilized eggs or uncleaved zygotes after the second phase of segregation have no effect on development, suggesting that a gastrulation center is established by transient localization of myoplasm in the VP region. The function of the gastrulation center was investigated by comparing protein synthesis in normal and UV-irradiated embryos. About 5% of 433 labelled polypeptides detected in 2D gels were affected by UV irradiation. The most prominent protein is a 30 kDa cytoskeletal component (p30), whose synthesis is abolished by UV irradiation. p30 synthesis peaks during gastrulation, is affected by the same UV dose and has the same UV-sensitivity period as gastrulation. However, p30 is not a UV-sensitive target because it is absent during ooplasmic segregation, the UV-sensitivity period. Moreover, the UV target has the absorption maximum of a nucleic acid rather than a protein. Cell-free translation studies indicate that p30 is encoded by a maternal mRNA. UV irradiation inhibits the ability of this transcript to direct p30 synthesis, indicating that p30 mRNA is a UV-sensitive target. The gasturlation center may function by sequestration or activation of maternal mRNAs encoding proteins that function during embryogenesis. PMID- 1299369 TI - Cell movements and cell fate during zebrafish gastrulation. AB - The early lineages of the zebrafish are indeterminate and a single cell labeled before the late blastula period will contribute progeny to a variety of tissues. Therefore, early cell lineages in the zebrafish do not establish future cell fates and early blastomeres must necessarily remain pluripotent. Eventually, after a period of random cell mixing, individual cells do become tissue restricted according to their later position within the blastoderm. The elucidation of a fate map for the zebrafish gastrula (Kimmel et al., 1990), has made it possible to study the processes by which cellular identity is conferred and maintained in the zebrafish. In this chapter, I describe single cell transplantation experiments designed to test for the irreversible restriction or 'commitment' of embryonic blastomeres in the zebrafish embryo. These experiments support the hypothesis that cell fate in the vertebrate embryo is determined by cell position. Work on the spadetail mutation will also be reviewed; this mutation causes a subset of mesodermal precursors to mismigrate during gastrulation thereby leading to a change in their eventual cell identity. PMID- 1299370 TI - Gastrulation and the evolution of development. AB - The original eukaryotic cell may have possessed the key processes necessary for metazoan development--cell differentiation, patterning and motility--and these are present in the cell cycle. Protozoa also possess key patterning processes. It remains a problem as to why there should be two main modes of development--one based on asymmetric cell division and the other on cellular interactions. The latter may be related to asexual reproduction. The morphogenetic movements of gastrulation--as distinct from specifying the body plan--are highly conserved in a wide variety of organisms. This may reflect the requirement for patterning being specified in two dimensions, sheets of cells, and a third dimension being created by cell infolding. The origin of the gastrula can be accounted for in terms of Haeckel's gastrea theory--an early metazoan resembling the gastrula. Gastrulation in Cnidaria may resemble the primitive condition but there is nevertheless considerable diversity. While this may reflect, for example, yolkiness, it seems that there is little selection on developmental processes other than for reliability. Thus it is possible that the embryo is privileged with respect to selection and this may help account for the evolution of novel processes like the origin of the neural crest. Reliability is the key demand made on development. This may be provided by apparent redundancy. Since many developmental processes involve switches and spatial patterning reliability is provided by parallel buffering mechanisms and not by negative feedback. PMID- 1299371 TI - The midblastula transition, the YSL transition and the onset of gastrulation in Fundulus. AB - The first signs of cell motility appear in Fundulus toward the end of cleavage, after cleavages 11 and 12. When blastomers cease cleaving, their surfaces undulate and form blebs. At first, these blebbing cell remain in place. Gradually thereafter they begin movement, with blebs and filolamellipodia serving as organs of locomotion. Non-motile cleaving blastomeres have thus differentiated into motile blastula cells. This transformation corresponds to the midblastula transition of amphibian embryos. Gastrulation in Fundulus begins with vegetalward contraction of the external yolk syncytial layer. This causes narrowing of the E YSL and initiates the epibolic expansion of the blastoderm. Convergent movements of deep cells within the blastoderm begin toward the end of this contraction. The YSL forms as a result of invasion of the yolk cell cytoplasm by nuclei from open marginal blastomers during cleavage. These YSL nuclei then undergo five metachronous divisions. After this, they divide no more. YSL contraction begins approximately 1.5 hours after cessation of these divisions (21-22 degrees C). This cessation of nuclear divisions is preceded by a gradual decrease in rate. (1) The duration of each succeeding mitosis increases steadily and often some nuclei do not divide at mitosis V. (2) The duration of interphases between succeeding mitoses also increases, but to a much greater degree, and the longest interphase by far is the last one, I-IV, between mitoses IV and V. (3) The mitotic waves responsible for mitosis V move much more slowly than those for the first four mitoses and invariably decelerate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299372 TI - The patterning and functioning of protrusive activity during convergence and extension of the Xenopus organiser. AB - We discuss the cellular basis and tissue interactions regulating convergence and extension of the vertebrate body axis in early embryogenesis of Xenopus. Convergence and extension occur in the dorsal mesoderm (prospective notochord and somite) and in the posterior nervous system (prospective hindbrain and spinal cord) by sequential cell intercalations. Several layers of cells intercalate to form a thinner, longer array (radial intercalation) and then cells intercalate in the mediolateral orientation to form a longer, narrower array (mediolateral intercalation). Fluorescence microscopy of labeled mesodermal cells in explants shows that protrusive activity is rapid and randomly directed until the midgastrula stage, when it slows and is restricted to the medial and lateral ends of the cells. This bipolar protrusive activity results in elongation, alignment and mediolateral intercalation of the cells. Mediolateral intercalation behavior (MIB) is expressed in an anterior-posterior and lateral-medial progression in the mesoderm. MIB is first expressed laterally in both somitic and notochordal mesoderm. From its lateral origins in each tissue, MIB progresses medially. If convergence does not bring the lateral boundaries of the tissues closer to the medial cells in the notochordal and somitic territories, these cells do not express MIB. Expression of tissue-specific markers follows and parallels the expression of MIB. These facts argue that MIB and some aspects of tissue differentiation are induced by signals emanating from the lateral boundaries of the tissue territories and that convergence must bring medial cells and boundaries closer together for these signals to be effective. Grafts of dorsal marginal zone epithelium to the ventral sides of other embryos, to ventral explants and to UV-ventralized embryos show that it has a role in organising convergence and extension, and dorsal tissue differentiation among deep mesodermal cells. Grafts of involuting marginal zone to animal cap tissue of the early gastrula shows that convergence and extension of the hindbrain-spinal cord are induced by planar signals from the involuting marginal zone. PMID- 1299373 TI - Fate mapping the neural plate and the intraembryonic mesoblast in the upper layer of the chicken blastoderm with xenografting and time-lapse videography. AB - The disposition of the Anlage fields of the neural plate and the intraembryonic mesoblast in the upper layer of the chicken blastoderm was studied at the primitive streak stage prior to the regression of Hensen's node (stages 5V to 6V, L. Vakaet (1970) Arch. Biol. 81, 387-426). Chicken blastoderms were cultured by New's technique on a mixture of thin egg white and agar. The anterior half of the deep layer was reflected with a tungsten needle. A circular fragment of the upper layer was punched out with a pulled out Pasteur pipette and discarded. It was replaced with an isotopic and isopolar piece of quail upper layer that was punched out with the same pipette. The deep layer was replaced and the chimeras were reincubated for 24 hours. The xenografts were followed with time-lapse videography. After fixation, the quail cells were located using Le Douarin's quail nucleolar marker technique. Integrating the observations with time-lapse videography and the results of Feulgen stained sections, we have drawn a new fate map of the disposition of the Anlage fields in the upper layer of the chicken blastoderm at stages prior to the regression of Hensen's node (stages 5V to 6V). The disposition of the neural plate and of the notochord, somites, nephrotome and lateral plates was therefore determined before the Anlage fields are morphologically discernible. The pathway of the fields in the upper layer towards their disposition was documented with time-lapse videography in chimeric chicken blastoderms that developed normally. PMID- 1299374 TI - NCAM and its polysialic acid moiety: a mechanism for pull/push regulation of cell interactions during development? AB - Many cell adhesion molecules have a distinct pattern of expression and well defined role in cell-cell recognition. In contrast, NCAM is broadly expressed and perturbations of its function affect many diverse aspects of embryonic development. Evidence has been obtained suggesting that the molecule and its polysialic acid moiety serve not only to contribute to specific interactions, but also to regulate overall cell-cell apposition. In this latter mode, the molecule can have both a positive and a negative effect on a wide variety of contact dependent cellular events. PMID- 1299375 TI - Enhanced antitumor activity of daunomycin conjugated with antigastric cancer monoclonal antibody MGb2. AB - In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare an antibody-daunomycin conjugate. Daunomycin was modified by cis aconitic anhydride, and the derivative was linked to antibody, a carbodiimide reagent being used to produce peptide bonding. Four to five molecules of daunomycin were specifically bound per molecule of antibody, without severely impairing the pharmacological activity of daunomycin and with minimal loss of antibody activity. A tetrazolium dye colorimetric assay indicated that the MGb2 daunomycin conjugate exhibited selective cytotoxicity against human gastric cancer cells SGC-7901 in vitro. The tumor localization in BALB/c nude mice showed that the specific conjugate could recognize the tumor as efficiently as the unconjugated antibody. MGb2-daunomycin conjugate could significantly suppress the growth of human gastric carcinoma GAII inoculated under the renal capsules of BALB/c nude mice. Intraperitoneal injection of MGb2-daunomycin conjugate twice a week for 3 weeks at a dose of 1 mg/kg of drug gave a tumor inhibition rate of 91.58%, far more effective than free daunomycin or an irrelevant conjugate. PMID- 1299376 TI - Tumor growth changes responsiveness to and production of granulocyte-macrophage colony-stimulating factor during recognition of self MHC class II molecules. AB - Tumor growth decreases T-cell recognition of self major histocompatibility complex (MHC) class II molecules by inducing changes in splenic macrophage (M phi) phenotype and function. The current investigation shows tumor-induced alterations in autorecognition also are associated with changes in responsiveness to and production of granulocyte-M phi colony-stimulating factor (GM-CSF). In contrast to normal host (NH) M phi, tumor-bearing host (TBH) M phi failed to express higher MHC class II molecule density after exposure to GM-CSF. Autoreactive T cells stimulated by either NH or TBH M phi were suppressed by GM CSF. Inhibition of prostaglandin E2 (PGE2) synthesis reversed M-CSF-induced suppression of autoreactivity to NH M phi and, to a lesser extent, to TBH M phi. When TBH autoreactive T cells were stimulated by TBH M phi, autoreactivity increased when GM-CSF was added and PGE2 synthesis was inhibited. Although GM-CSF can contribute to tumor-induced suppression, it did not affect the contribution of GM-CSF during autorecognition. Increased GM-CSF production was responsible, at least in part, for the TBH M phi-mediated suppression. Low concentrations of GM CSF were produced endogenously by tumor isolates, and GM-CSF production was significantly increased when isolates were stimulated with lipopolysaccharide. Autoreactive T cells stimulated solely by TBH M phi produced more GM-CSF than autoreactive T cells stimulated by NH M phi. Cultures supplemented with several concentrations of NH or TBH M phi produced similar amounts of GM-CSF in a dose dependent manner. Inhibition of PGE2 synthesis by NH and TBH M phi reduced GM-CSF production equally. Collectively, these results suggest that during tumor growth, responsiveness to and production of GM-CSF alters recognition of self MHC class II molecules. PMID- 1299377 TI - p53 gene mutation in primary human renal cell carcinoma. AB - We searched for possible mutations in the entire coding region of tumor suppressor gene p53 in primary human renal cell carcinomas using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. We found p53 mutations in 2 of 21 cases (10%). DNA sequencing of the polymerase chain reaction products verified that the first case included a 17-base deletion at the beginning of exon 6. The second case showed a T to C transition at nucleotide 1328 in exon 7. No clinical or pathological similarity was found in the renal cell carcinomas containing the mutated p53 genes. Present results suggest that p53 mutation is involved at low frequency in human renal cell carcinomas. PMID- 1299378 TI - Folate-binding protein mRNA is decreased in methotrexate-resistant KB cells. AB - Folate-binding protein (FBP), a high-affinity folate receptor expressed in certain malignant and normal cell lines and tissues, is responsible for cellular transport of folate and structurally related antifolates such as methotrexate in human KB (nasopharyngeal carcinoma) cells. We have developed a sensitive polymerase chain reaction (PCR) assay to quantitate folate-binding protein mRNA levels. This assay was tested in KB and methotrexate (MTX)-resistant KB (KB1BT) cell lines. Based on assay results, we conclude there are 245 molecules of folate binding protein (FBP) mRNA per KB cell, and there is an approximately 3-fold decrease in FBP mRNA levels per KB1BT cell. The data obtained by quantitative PCR correlate well with northern blot analysis of mRNA levels and membrane-associated folate-binding protein (M-FBP) levels. Moreover, when KB1BT cells were grown in the absence of MTX for 8 months, the levels of FBP and M-FBP mRNA did not change, and there was a substantial decrease in MTX uptake, compared with KB cells. PMID- 1299380 TI - Reference listings in cancer research. PMID- 1299379 TI - Increased deoxycytidine kinase activity in cancer cells and inhibition by difluorodeoxycytidine. AB - The activity of deoxycytidine kinase (EC 2.7.1.74), an important pyrimidine salvage enzyme, was elevated 5- to 30-fold in human ovarian carcinoma and OVCAR-5 cells, in human colon carcinoma and HT-29 cells, in rat hepatoma 3924A solid tumors and cells, and in rat sarcoma as compared with the respective control normal cells. There was an inverse relationship between cell doubling time and deoxycytidine kinase activity in 8 cancer cell lines, with rapidly growing HL-60 cells (20 hr) showing the highest, and slower-growing lung H69 cells (60 hr) the smallest, increase in enzyme activity. In time-sequence studies in human HL-60, OVCAR-5, PANC-1, and rat hepatoma 3924A cells, there was a significant rise in deoxycytidine kinase activity after 3-6 hr of seeding, with peak increases (3.5- to 4-fold) at 48-72 hr in the log phase in comparison with values of the respective plateau phase cells (96-144 hr). In extracts of various cancer cells, the high deoxycytidine kinase activity was competitively inhibited by difluorodeoxycytidine (DFDC), with Ki = 7 to 30 microM. The Km for deoxycytidine in various carcinoma cell lines ranged from 0.3 to 0.7 mM and addition of DFDC increased the apparent Km from 0.7 to 4 mM. Deoxycytidine kinase activity in human HL-60 cells was inhibited by the end product, dCTP, with IC50 = 3 microM; dCTP elevated the Km for deoxycytidine from 0.35 to 0.9 mM. dTTP reversed the inhibition by dCTP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299381 TI - Single gene mutations in early embryonic loss. PMID- 1299382 TI - Controversies and opinions in embryo culture: two- to four-cell transfer vs blastocyst. PMID- 1299383 TI - The neglected human blastocyst. PMID- 1299384 TI - Microscope-delivered ultraviolet laser zona dissection: principles and practices. PMID- 1299385 TI - A correlation of the outcome of clinical in vitro fertilization with the inositol content and embryotrophic properties of human serum. AB - PURPOSE: This study was designed to investigate whether the level of myo-inositol (MI) in human serum is critical for embryotrophic activity. METHODS: The embryotrophic properties of human serum were evaluated by the development of postimplantation mouse embryos [in vitro assay of Tam et al. (Fertil Steril 48:834-839, 1987)]. An enzymatic spectrophotometric method using myo-inositol dehydrogenase was used for determination of serum MI. The level of MI detected in serum was compared with the embryotrophic properties and the pregnancy outcome. The effect of MI on the embryotrophic activity of human serum was studied by supplementing the suboptimal serum samples that were unsupportive of embryo growth with extra MI. RESULTS: Serum obtained from patients having successful IVF pregnancies generally supported better development of postimplantation mouse embryos and contained higher levels of inositol, particularly if the serum sample was collected during the IVF treatment cycle. Serum samples obtained from patients with aborted pregnancies, though supporting mouse embryo development, contained significantly lower concentrations of inositol. An improvement of the embryotrophic properties with exogenous inositol supplement was achieved in some but not all of the suboptimal serum samples studied. CONCLUSIONS: It is possible that other factors in addition to inositol are crucial in promoting better embryonic development. PMID- 1299386 TI - Effect of the number and depth of embryos transferred and unilateral or bilateral transfer in tubal embryo transfer (TET). AB - PURPOSE: Our purpose was to evaluate the possible effects of the number of embryos transferred, the depth of embryos placed within the tube(s), and unilateral or bilateral tubal transfer on pregnancy initiation in tubal embryo transfer (TET). METHODS: One hundred eight consecutive TET cycles were analyzed. Oocyte retrievals were carried out by transvaginal ultrasound-guided aspiration of follicles. Forty-eight hours after oocyte retrieval, the developing embryos at the stage of two to four cells were transferred into the fallopian tube(s) by laparoscopy. A maximum of four embryos was transferred to each patient. RESULTS: The pregnancy rates were similar among the cycles in which two, three, or four embryos were transferred. In addition, there was no significant difference in the pregnancy rate whether the embryos were deposited > 4 cm or between 3 and 4 cm into the tube(s). Although the pregnancy rate was greater in cycles of bilateral tubal transfer, the difference from that of unilateral transfers was not significant. CONCLUSION: Our data indicate that when two to four embryos were transferred and the embryos were placed > or = 3 cm within the tube(s), unilateral or bilateral tubal transfer had little influence on the ultimate success of TET. PMID- 1299387 TI - Spectrophotometric absorbance of follicular fluid: a selection criterion. AB - PURPOSE: The aim of this study was to ascertain the absorbance profiles of uncontaminated follicular fluids (FF) vs blood and medium contaminated FF, and to test the hypothesis that blood contamination alters the biochemical status of FF. METHODS: FF (n = 655) from 230 patients were scanned spectrophotometrically during an ongoing in vitro fertilization (IVF) program. Based on spectrophotometric evaluation, blood contaminated and uncontaminated FF (n = 39 patients/FF) were analyzed for electrolyte content, inorganic phosphate, glucose, creatine, urate, total protein, albumin, bilirubin, cholesterol, alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase, aspartate transaminase, and lactate dehydrogenase by means of a SMAC analyzer. RESULTS: Laparoscopic aspiration resulted in the collection of significantly more clear FF compared to the transvaginal procedure (P = 0.001). Uncontaminated fluid depicted a single mean absorbance at 458.0 nm. Blood contaminated FF could be identified by spectrophotometry and revealed three peaks at 418.12, 540.13, and 575.32 nm, respectively, according to the degree of blood contamination. Follicular fluid diluted with Earles Balanced Salt Solution (EBSS) displayed an additional mean peak at 561.4 nm. Potassium, glucose, and all of the above mentioned enzymes revealed significantly higher levels in blood contaminated FF (P < 0.05). CONCLUSIONS: From this study, it is concluded that blood contamination and dilution with culture medium influence the biochemical composition as well as the absorbance spectrum of follicular fluids. This procedure is advocated as a prerequisite before quantifying FF content. PMID- 1299388 TI - Embryonic behavior of two-cell mouse embryos frozen by the one- and two-step ultrarapid techniques. AB - PURPOSE: A modified two-step ultrarapid freezing technique was compared to the one-step ultrarapid freezing technique. Two-cell mouse embryos were frozen-thawed using the two freezing protocols, and postthaw cryoprotectant removal was carried out in either a single- or a multiple-step procedure. RESULTS: Statistically similar cryosurvival (96.95-100%) and blastocyst formation rates (87.95-91.47%) were obtained with both freezing groups. In addition, the method of cryoprotectant removal did not have any significant effect on the survival and development of the frozen-thawed embryos in both groups. Blastocysts formed following single-step cryoprotectant removal had significantly lower inner cell mass counts in the one-step than in the two-step group (26.14 and 27.59, respectively; P < 0.05). Embryo transfer studies showed that the implantation and fetal formation rates of embryos frozen by the two-step technique (61.67 and 60.0%, respectively) were similar to those of embryos frozen by the one-step technique (74.12 and 71.76%, respectively). CONCLUSION: These results demonstrate that the ultrarapid two-step technique is as effective in cryopreserving two-cell mouse embryos as the ultrarapid one-step technique. PMID- 1299389 TI - The YAG laser used in micromanipulation to transect the zona pellucida of hamster oocytes. AB - PROBLEM: Since there has been no reported use of the YAG laser to micromanipulate oocytes, our purpose was to study whether (1) a YAG laser could be used to open the zona pellucida of hamster oocytes; (2) human sperm could reach the ooplasm and (3) under sperm penetration assay conditions, sperm would bind and penetrate the ooplasm. RESULTS: A YAG 100 laser was used at 10 W and 0.4-sec pulse width to open eight of eight ooplasm oocytes. The opening in the zonae was 0.25 to 1.0 rad (10 to 40 microns). For the initial eight oocytes and two parallel controls, the coarse appearance of the ooplasm was unchanged after 3 days. Next, in 11 of 12 manipulated oocytes, the sperm clustered at the opening of the zona. When 16 more oocytes were opened and exposed to sperm in sperm penetration assay conditions, each ooplasm bound sperm. There was no penetration noted. Each manipulation time was < 1 min. To clarify the laser effect, oocytes were exposed to laser energy then utilized as the interactive surface in the sperm penetration assay. It was found that only 20% bound sperm with no penetration. CONCLUSION: While the time factor compares favourably with other methods of zona opening, further study needs to be performed to minimize effect to the exposed oocyte. PMID- 1299390 TI - In vitro DNA fluorescence after in vitro fertilization (IVF) failure. AB - PURPOSE: A pilot study was performed to test the diagnostic value of in vitro DNA fluorescence in oocytes that failed to fertilize after IVF. Ten patients with a cleavage rate less than 20% after IVF were included. RESULTS: Uncleaved oocytes were observed by fluorescence microscopy after incubation with the DNA fluorescent dye Hoeschst 33342. Four main causes which may have contributed to the low cleavage rate were found: (1) sperm incapacity to penetrate the oocyte despite the absence of the usual criteria for male infertility, (2) oocyte immaturity, (3) delayed fertilization, and (4) oocyte abnormalities revealed by aberrations in the morphology of the female chromatin. CONCLUSIONS: The possibility of a rapid and detailed analysis of the maturational status of unfertilized oocytes, the morphology of the female chromatin, the presence and quantity of spermatozoa tightly bound to the zona pellucida, and sperm penetration into the oocyte without subsequent pronucleus formation, using DNA fluorescence, allows us to clarify further the cause of fertilization failure and to orient infertility treatment toward the male, the female, or both partners. PMID- 1299392 TI - A simplified method for processing sperm obtained during microsurgical epididymal sperm aspiration (MESA) for use in in vitro fertilization. PMID- 1299393 TI - Microinjection pregnancy following cryopreservation. PMID- 1299391 TI - Visualization of second polar body chromosomes in fertilized and artificially activated mouse oocytes treated with okadaic acid. AB - OBJECTIVE: Our objective was to develop a new reliable method for cytogenetic analysis of the chromosome set in second polar bodies (PBs) from one-cell-stage mouse embryos. SETTING: The study took place at the Reproductive Biology and Experimental Cytogenetics Laboratories. METHODS: Oocytes from F1 hybrid and T6/T6 mice were fertilized in vitro and artificially activated with ethanol. Zygotes, parthenogenetic embryos, and isolated second PBs were treated with 10 microM okadaic acid (OA) for 1-2 hr, further cultured in plain medium, and fixed. Chromosomal preparations were made and C-banded, and the number of chromosomes in second PBs and embryos was counted. RESULTS: OA-induced nuclear envelope breakdown in pronuclei as well as in second PB nuclei. Countable chromosome plates were obtained in 92-93% of second PBs treated 4-4.5 hr after activation. The T6 marker chromosome could easily be recognized in second PBs from T6/T6 mice. A haploid set of chromosomes was obtained in 18 of 19 isolated second PBs treated with OA 4-5 hr after activation. CONCLUSION: Treatment of second PBs with OA allows visualization of the PB chromosomes. Cytogenetic analysis of the second PB and the corresponding oocyte constitutes a new approach for the study of meiotic nondisjunction in experimental cytogenetics. The chromosomal study of isolated second PBs seems to be promising for clinical preimplantation cytogenetics. PMID- 1299394 TI - [The pulmonary manifestations in AIDS]. AB - Clinical and paraclinical experience in HIV infection, though the time elapsed since the first observations is relatively short, begins to get typical outlines. In the case of AIDS, the lung is the main place of opportunistic infections, other inflammatory processes and neoplasia. The present work deals with six clinical cases with positive serum tests for HIV and secondary respiratory phenomena such as: Kaposi sarcoma, pneumonia with Pneumocystis carinii, tuberculosis, candidosis, pneumonia with common germs. Particular aspects of treatment and disease evolution are commented. PMID- 1299395 TI - [Broncho-Vaxom in the treatment of chronic pulmonary lesions]. AB - Two hundred patients with various chronic pulmonary diseases were treated with the bacterial lysate Broncho-Vaxom (BV) in addition to conventional treatment, or alone, over a period of 2 years. The efficacy of BV was assessed ob the basis of clinical symptoms (dyspnoea, cough, expectoration, fever and bronchial rales), pulmonary function, number of relapses and immune status, in particular serum immunoglobulins A, G and M. The results demonstrated the efficacy of BV in the treatment and prevention of chronic pulmonary disease. In patients treated with BV, clinical symptoms improved significantly compared to controls, incidence of infectious episodes was reduced and impaired immune functions were restored. BV was generally well tolerated. PMID- 1299396 TI - [The late evolution of bronchial asthma appearing in children]. AB - A retrospective study was performed in order to compare the clinical evolution of chronic bronchial asthma with onset in childhood with that of bronchial asthma registered at adult age. The group included 150 cases (87 females and 63 males) out of which 108 (72%) asthma with late onset and 42 (28%) asthma symptoms registered in childhood and adolescence. The symptoms were: allergic rhinitis and spastic tracheobronchitis in 18 (42.8%), dyspneic recurrent bronchitis in 16 (38%), nasal polyposis in 4 (9.5%) and atopic dermatitis in 4 (9.5%) cases. A possible allergic etiology was not taken into consideration in these cases. According to the data obtained, it results that the evolution and the prognosis of bronchial asthma are more severe in patients with its onset in childhood, where there were noted: more severe clinical forms of the disease, higher ventilation dysfunction, more numerous social (family) consequences of the disease, and a higher necessity of long term, systemic corticotherapy than in cases of bronchial asthma with late onset. The delay in the preventive treatment or an incorrect application of it in childhood will condition to a great extent the unfavourable evolution of the disease. PMID- 1299398 TI - [Homeopathy and the vital force]. PMID- 1299397 TI - [Endothoracic sarcoidosis--a disease with atypical manifestations?]. PMID- 1299399 TI - Why the treatment with Reprimun could be efficient for tuberculosis prevention in HIV infected individuals. PMID- 1299400 TI - [Training notebook]. PMID- 1299401 TI - [The respiratory manifestations in the picture of phakomatosis]. AB - After a short review of phakomatosis nosology, the paper deals with 3 clinical cases, out of which two of Recklinghausen neurofibromatosis and one of tuberous sclerosis (Bourneville's disease), all of them with pulmonary determinations, confirmed bioptically and histopathologically. A "florid" cutaneous syndrome (including all the variants of skin lesions) dating from childhood, subsequently accompanied by phenomena of psychical involution and behaviour troubles were present in two cases; retinal lesions were also associated in the third case. Visceral intrapulmonary determinations (i.e. diffuse interstitial fibrosis, and even bronchopulmonary neoplasm in one case) were registered in all cases, too. The diagnostic importance of investigating all apparatus, systems and organs which can be jointly involved in phakomatosis is emphasized. The importance of an inquiry regarding family history is also noticed. For the studied cases, the contribution of complementary (psycho-neurological, ophthalmological, orthopaedic a.s.o.) examinations--though quite valuable--took a back seat in comparison with the essential elements provided by the dermatological and histopathological examinations. PMID- 1299402 TI - [The exclusively outpatient treatment of pulmonary tuberculosis under the conditions in Romania]. AB - In order to demonstrate the possibility of an exclusively outpatient treatment of pulmonary tuberculosis in the present conditions in our country, a study was performed on 140 cases in Bucharest. The admission criteria were as follows: sputum negative patients (M-C-); paubacillary cases, sputum positive only in culture (M-C+); Tb pleuritis; patients refusing hospitalization, regardless their bacteriological status, and sputum positive cases also at smear examination (M+C+), if they had no household contacts under 20 years of age or with a good social economic standard of life. The patients were given the intensive chemotherapy regimen HSRZ 2/7 for 6 months, that was prolonged to 9 months in specified cases. A number of 31 patients were non-bacillary (M-C-) out of which 14 cases with pleuritis; 70 were paucibacillary (M-C+), and 39 were smear positive (M+C+). Out of 109 patients which were bacteriologically confirmed, sputum reversion in culture was obtained in 71.6% of cases at 2 months and in 89.0% at 3 months. At treatment end, sputum negativation was not obtained in a single patient (0.9%). Case follow-up for 6-41 months after treatment end led to the registration of 8 therapeutical failures and bacteriological relapses (5.7%). Five cases recovered through re-treatment, 1 patient (0.7%) died through tuberculosis, and 2 (1.4%) became chronic case. Periodical control of the 95 contact children in the respective households revealed a single conversion of the tuberculin reaction and no Tb case after treatment start in index cases, which proves the epidemiological reliability of the method. PMID- 1299403 TI - [Acute rhinopharyngitis, acute interstitial pneumonia and parieto-frontal brain abscess with H. influenzae type B]. AB - The paper deals with a parietal frontal cerebral abscess caused by HITB biotype I in a girl aged 8 months. First a meningitis is suspected, then a tuberculous meningitis unsuccessfully treated with ampicillin, biseptol, respectively INH, rifampicin, pyrazinamide, prednisone, phenobarbital and chloramphenicol. The patient died through a central respiratory standstill on the 17th day of disease. The anatomopathological examinations revealed a giant parietal frontal cerebral abscess. H.influenzae, (serum type B, biotype I) resistant to ampicillin, chloramphenicol, Kanamycin, rifampicin and tetracycline but sensitive to erythromycin and neomycin was also found. A pharyngeal infection with HITB was presumably the origin of the abscess. PMID- 1299404 TI - Beclomet and cromolyn--two therapeutical certitudes. PMID- 1299405 TI - [Ciprofloxacin, the most efficacious quinolone in the therapy of infectious respiratory lesions]. PMID- 1299406 TI - [A case of intrathoracic variable stenosis demonstrated by flow-volume curve morphology]. PMID- 1299407 TI - [Intrapleural analgesia via a percutaneous catheter]. PMID- 1299409 TI - Isolation, stabilization, and molecular weight estimation of thyroid hormone receptors of tadpole and chick embryo erythrocytes. AB - Typical procedures for the isolation of triiodothyronine (T3) receptors from mammalian nuclei involve extraction of nuclei with buffers containing divalent cations and 0.40M KCl. However, when applied to tadpole erythrocyte (RBC) nuclei, this method gave low yields of relatively unstable T3 receptors. The use of EDTA (10 mM) and 0.4M KCl in a sucrose-Tris buffer resulted in the extraction of 90% of the specifically bound [125I]-T3 from RBC nuclei. It was also found that 5 mM thiol reagent (DTT, GSH, or beta-mercaptoethanol) was required for maximal stability of the receptor. Fractionation of labeled RBC nuclear extracts on a Sephadex G-100 column yielded only one peak of specific T3 binding activity. The T3 receptor peak eluted at the same position as bovine serum albumin (BSA), with an estimated mol wt of 68 kDa. Specific T3 binding activity was destroyed by protease digestion but not by DNAse or RNAse. Scatchard analysis of the fractions from the receptor peak supported the existence of one class of T3 binding sites, with an estimated Kd (about 7 pM) comparable to the Kd reported for the intact RBC. Using the same methods, T3 receptors from the nuclei of chick embryo RBCs were also isolated, again with a Kd (7 pM) similar to that for the intact RBC. The chick receptor also eluted from the Sephadex G-100 column at the same position as BSA. The estimated mol wt of the T3 receptors from both sources is comparable to those reported for T3 receptors from other sources. The results show that T3 receptors derived from both tadpole and chick RBC nuclei could be isolated in a soluble and stable form with no apparent change in Kd. PMID- 1299410 TI - A novel, highly conserved structural motif is present in all members of the steroid receptor superfamily. AB - Steroid and thyroid hormone receptor superfamily members are ligand potentiated transcription factors. Recent evidence indicates that one aspect of steroid receptor action is an interaction with other trans-acting factors, such as the glucocorticoid receptor with the AP1 transcription factor, for example. Using a structural approach to identify domains of the glucocorticoid receptor responsible for interactions with affiliated transacting factors and DNA, we have identified a putative helix-turn-zipper motif that is conserved in all steroid, thyroid hormone, retinoic acid, and vitamin-D3 receptors. This structural motif is also conserved among new members of the family, the peroxisome proliferator activated receptors and the retinoid-X receptors. This structural domain is characterized by a pair of amino acids (I,L,V)P that is conserved in all superfamily members. Additional characteristics include six heptad repeats of hydrophobic amino acids, four of which form a canonical leucine zipper in the rat glucocorticoid receptor. Although this leucine repeat is not absolutely conserved among superfamily members, the periodicity of hydrophobic residues is conserved throughout. Based on sequence analyses from the GenEMBL and SwissProt databases using the Genetics Computer Group and MacVector sequence analysis software packages, and the Brookhaven structural database, we present evidence for a novel structural domain, a helix-turn-zipper that is conserved in all superfamily members, and may function in transactivation of cognate genes. PMID- 1299408 TI - [The evolution and structure of morbidity from extrarespiratory tuberculosis in the last 15 years in Romania]. AB - Though in comparison with the overall lethality of tuberculosis the extra respiratory localizations of the disease showed a markedly less weight than the respiratory ones during the past 15 years (12.8% in 1975 and 6.7% in 1989), this pathology chapter is still essential due to the diversity of Tb forms and localizations. The annual average rate of the decrease in extra-respiratory tuberculosis incidence was of 4.8% between 1975-1989, so the incidence value reached 4.2%000 at the end of the last year of study. Just like 15 years ago, in 1989 the extra-respiratory tuberculosis incidence was dominated by the localizations on the peripheral lymph nodes (1.2%000), on bones and joints (1.0%000), urogenital apparatus (0.7%000), meninges and central nervous system (0.5%000). The prevalence of patients with extra-respiratory Tb localizations was gradually diminished so that only 3415 cases were registered in the IIIrd group of the active case-index in 1989 (13,524 in 1975). More than half of the number of deaths through extra-respiratory tuberculosis were still due to tuberculous meningitis, particularly in children aged 0-4 years (82% of deaths in 1989). A further diminution up to a total elimination of extra-respiratory Tb localizations (still about 1,000 new cases a year) can be reached only by a restriction and liquidation at the same time of both primary and secondary pulmonary tuberculoses. PMID- 1299411 TI - Angiotensin II receptor subtypes in rat renal preglomerular vessels. AB - A simple technique to isolate rat renal preglomerular vessels is described. Kidneys were pressed against a 0.3 mm stainless steel grid. The whole vascular tree, including the interlobar, arcuate, and interlobular arteries, as well as the afferent arterioles, remained on the grid surface from where they were recovered. Extensive washing yielded a highly pure preparation of renal microvessels. Radioligand binding experiments were performed to characterize 125I [Sar1,Ile8]-ANG II binding sites in preglomerular microvessel membranes. Equilibrium saturation binding experiments revealed the presence of one group of high affinity receptors (Kd = 1.22 +/- 0.171 nM; Bmax = 209 +/- 14 fmol/mg protein). Competitive inhibition experiments with two highly specific nonpeptide ANG II antagonists, losartan (DuP 753), which is specific for the AT1 receptor subtype, and PD123319, which is specific for the AT2 subtype, demonstrated that the large majority of, if not all, ANG II receptors in rat renal preglomerular vessels correspond to the AT1 subtype. PMID- 1299412 TI - The double life of the IGF-1 receptor. AB - The IGF-1 receptor is expressed in many cell types, and its activation by its ligands is a required step for the proliferation of many cells in vivo and in vitro. In most cells in culture, requiring more than one growth factor for growth, the IGF-1 receptor can be found in one of two different modes: in the first mode, although it is autophosphorylated by its ligands and induces the expression of specific genes, it does not transmit a mitogenic signal. In the alternative mode, i.e., after priming with an unrelated growth factor, the IGF-1 receptor responds to its ligands with a mitogenic stimulus. This review examines briefly the possible alternatives to explain this different behavior, which is crucial to our understanding of the control of cellular proliferation. PMID- 1299413 TI - Reflux nephropathy in adults. AB - Reflux nephropathy (RN), the main complication of the vesico-ureteral reflux (VUR), relatively frequent in adults, is often the consequence of recurrent urinary infections in the child, hood or during pregnancy. Unilateral RN has generally a benign course but the bilateral one, with important nephron destruction, leads to focal and segmental glomerulosclerosis, manifested by high levels of proteinuria. A certain degree of cicatrization and renal failure are followed by progressive impairment of the remaining renal function, even if VUR is cured. An early diagnosis, treatment of the acute bacterial infection, adequate ingestion of liquids, regulation of the intestinal transit and complete bladder voiding by miction, associated with hypotensive and antiinfectious drug therapy lead to VUR disappearance in 80% of the cases, avoiding renal failure. Surgery is indicated only in the patients with severe reflux and with congenital or obstructive anomalies, as well as in the case of recurrent infection resistant to antibiotherapy. PMID- 1299414 TI - Myocardial involvement in systemic lupus erythematosus and systemic sclerosis- pulsed Doppler echocardiographic evaluation of left ventricular diastolic function. AB - Myocardial involvement (MI) in connective tissue diseases is commonly found at autopsy but seldom recognized clinically. To assess the subclinical MI, the left ventricular (LV) diastolic function was studied in 16 patients with systemic lupus erythematosus (SLE) and 15 patients with systemic sclerosis (SSc) by means of pulsed Doppler echocardiography. Patients with abnormal LV systolic function were not included. A control group (C) included 16 sex and age-matched healthy subjects. The parameters analyzed were: peak early diastolic flow velocity (E), peak late diastolic flow velocity (A), E/A ratio, isovolumic relaxation time (IRT). LV diastolic function was found impaired in SLE and SSc patients even when systolic function was normal as could be demonstrated by pulsed Doppler echocardiography. PMID- 1299415 TI - Contribution of the high amplitude electrocardiography to the detection of ventricular late potentials in several cardiovascular diseases. AB - The criteria for detection of ventricular late potentials (VLP) by high amplitude electrocardiography (ECG) in the frequency domain were evaluated in 75 patients with cardiovascular diseases, mostly men (85%), with a mean age of 57 years, distributed by disease type into three subgroups: (1) with a history of myocardial infarction (MI)--53 cases; (2) with syncopes, episodes of prolonged ventricular arrhythmias--18 cases; (3) with unobstructive, primary cardiomyopathies--4 cases. Complete clinical examination, standard ECG, continuous 24 hr Holter ECG, high amplitude ECG (Corazonix system) for detection of VLP by analyses in the time domain (TD) and in the frequency one (FD) were performed in all the cases. The VLP incidence was evidently high in all the cases. By association of the analyses in TD and FD, the accuracy of VLP detection increased by 17.3% in the whole group (from 64% to 81.3%). The incidence of severe ventricular arrhythmias (class 4-5 Lown, i.e., doubled and/or trebled ventricular extrasystoles, salvos of unsustained ventricular tachycardia) was evidently higher in the patients with VLP (88% compared with 77% in the absence of VLP), thus demonstrating the presence, in most of the patients studied, of an arrhythmogenic mechanism by ventricular reentry. PMID- 1299416 TI - The prognostic value of late ventricular potentials for sudden death. AB - Sixty patients of whom 51 with old myocardial infarction--30 with late ventricular potentials and 30 without--were followed up for 5 years. The late ventricular potentials were recorded using an original method. During the follow up period, in the group, with late ventricular potentials, sudden death was recorded in 6 patients and episodes of ventricular tachycardia in 2. No sudden death occurred in the patients without late ventricular potentials. The prognostic value of this simple, noninvasive technique is emphasized. PMID- 1299417 TI - Serum cholesterol and apoprotein B levels and serum cholinesterase activity in selected hematologic malignancies. AB - As compared to values recorded in 10 healthy normal-weight normolipidemic control subjects, serum cholesterol and apoprotein B levels as well as serum cholinesterase activity were found to be obviously decreased in the 28 patients with acute leukemia, the lowest levels being associated with the worst prognosis. The values of the above-mentioned biochemical variables in the 21 patients with chronic disorders (13 with chronic myeloproliferative disease and 8 with chronic lymphocytic leukemia) were not as low as in patients with acute leukemia. It should however be mentioned that in patients with chronic myelogenous leukemia, the lowest levels of serum cholesterol were correlated with a large tumor burden as assessed by a score taking into account for clinical and hematologic parameters. It is concluded that hypocholesterolemia could be regarded as a factor of adverse prognosis in hematologic malignancies, being probably the result of both enhanced catabolism of low density lipoproteins and impaired hepatic lipoprotein synthesis. PMID- 1299418 TI - Pattern of antigens A and B distribution on the surface of AB group red blood cells--an argument in support of the concept of "genetic oscillation". AB - Using a mixture of mouse monoclonal antibodies anti red blood cell (RBC) AgA and human antibodies anti RBC AgB coupled to fluorescein isothiocyanate (FITC) conjugated goat antimouse monoclonal antibodies and to phycoerythrin (PE) conjugated goat antihuman monoclonal antibodies, we obtained the distribution of these antigens on the AB RBC surface. The analysis of 30 samples of 30,000 100,000 RBCs each was carried out using flow cytometry and revealed three kinds of AB RBC populations: (1) a population characterized by maximum concentration of AgA and minimum concentration of AgB; (2) a complementary population characterized by minimum concentration of AgA and maximum concentration of AgB; (3) an intermediary equilibrated population with about equal concentrations of the A and B antigens. This pattern corresponds to the pattern of oscillating genetic activity defined as "genetic oscillation", a concept amply discussed in the paper. PMID- 1299419 TI - Hypertrophic osteoarthropathy secondary to bronchopulmonary cancer (our experience). AB - During 5 years (1986-1990), 81 of the patients under our care showed bronchopulmonary cancer diagnosed by clinical, x-ray and bronchoscopic examinations. Of these, 69 (85.2) were men and 12 (14.8%) women, with a mean age of 62 years; 72 patients (90%) were moderate or heavy smokers. Four of them (4.9%) presented the classical hypertrophic osteoarthropathy (HOA) described by Bamberger and Pierre Marie, i.e., finger clubbing, ossifying periostitis of the long bones, joint pains and swelling. Other 3 patients showed only finger clubbing, while 7 of 30 cases studied by systematic x-ray examinations of the long bones presented ossifying periostitis (5 cases) or hyperostosis (2 cases). It results that almost one third (31.6%) of the patients with bronchopulmonary cancer had a complete or incomplete Bamberger-Pierre Marie syndrome. It is concluded that HOA identification before the clinical and x-ray manifestations of bronchopulmonary cancer could contribute to an early diagnosis of this malignant disease. PMID- 1299420 TI - Age-dependent variations of the plasma peroxides and total antioxidants in women with obesity and hypothyroidism. AB - The concentrations of peroxides, total antioxidants and free sulfhydryl (SH) groups in the plasma of normal persons vary depending on age and sex. The most significant differences for peroxides were found between young and old people over 60 years in both sexes. For the SH groups, significant differences were observed only between young and older women, while in men, similar differences were found only for total antioxidants. In women, the association of obesity with hypothyroidism induces a significant increase of peroxides even at the age of 35 years. This significant increase goes in parallel with a increase of uric acid and a decrease of the total antioxidants. Considering the inclusion of uric acid and of free SH groups among the natural antioxidants, the changes observed in obesity associated with hypothyroidism may suggest a tendency of an adaptation of the organism since hypothyroidism favors the peroxidation of lipids. Up to a certain age, varying according to the individuals, the rise of lipid peroxides is compensated by the increase of certain antioxidants, especially of uric acid. PMID- 1299421 TI - Highly active effect of alpha interferon in blocking the cutaneous delayed hypersensitivity. AB - A group of 13 patients with contact dermatitis to various chemical compounds such as potassium dichromate, nickel sulphate, formaldehyde and balsam of Peru, was investigated by patch test and by the agreement between the history of disease and the patch test, the specific allergen involved in each special case could be demonstrated. Two-three days after the first patch test three normal skin areas were chosen. The first area was intradermally infiltrated with alpha-2a Interferon (IFN) (100,000 I.U. in 1 ml), the second area was infiltrated with saline and the third area, considered as control, did not receive any treatment. Once more the corresponding allergen was applied into the skin in a second patch test. After 48 hours in the IFN infiltrated area, only the delayed contact hypersensitivity become negative thus proving that alpha-2a IFN behaves as an efficient inhibitor of these immune effector reactions. Since the lymphocytes involved in the delayed type hypersensitivity reactions (in our case contact dermatitis) belong to the T helper line, i.e., are CD-4 positive cells we conclude that alpha-2a IFN in vivo is an efficient inhibitor of the activation of these cells. This effect achieved by any CD-4(+) DTH clones does not depend on their antigenic specificity. Some clinical trials are now in progress in our laboratory to turn to account this important biological effect in the clinical practice as an efficient inhibitor in skin contact dermatitis. PMID- 1299422 TI - Therapeutic modalities in severe infections. Theoretic considerations. AB - The advantages of discontinuous versus continuous antibiotherapy are discussed as a therapeutic method in severe infections. The main scientific achievements related to the criteria of discontinuous antibiotherapy are discussed as a therapeutic modality consisting in administration of moderate doses of usual antibiotics every 12th hours. The advantages and disadvantages of the classical continuous and discontinuous antibiotherapies are presented and amply discussed. PMID- 1299423 TI - Effect of calcium blocking agents of the verapamil series on the myocardium mitochondrial activity in experimentally induced arterial hypertension. AB - Some mitochondrial biochemical parameters were determined in Wistar rats with experimentally induced arterial hypertension (AHT) treated with calcium blocking agents of the Verapamil series. The results obtained showed that succinic dehydrogenase (SDH) activity increased, in the group with AHT, by 23.4% as compared with the control group while in the group with AHT treated with Verapamil the activity of this enzyme increased by 46.7%. The NAD+ dehydrogenase activity showed a moderate increase (15.7%) in the group with AHT and an increase by 22.3% after administration of Verapamil. The mitochondrial content in thiolic groups presented an increase of 12.5% in the group with AHT and of 24.4% in the treated group. The kinetics of the mitochondrial swelling-contraction also presented changes in as much as the cycle period, first increased then partially returned to normal values after Verapamil treatment. The strongly stimulating effect of Verapamil on the enzymatic activity in the Krebs cycle was also demonstrated. PMID- 1299424 TI - Outbreak of influenza A in a nursing home--New York, December 1991-January 1992. PMID- 1299425 TI - Tropical health notes. PMID- 1299427 TI - Prevalence of hepatitis C virus infection among patients with inherited bleeding disorders in Newfoundland. PMID- 1299426 TI - Nosocomial hepatitis B associated with orthopedic surgery--Nova Scotia. PMID- 1299428 TI - Non-O1 Vibrio cholerae enterocolitis in Quebec tourists returning from the Dominican Republic. PMID- 1299429 TI - Cholera and international air travel. PMID- 1299430 TI - Gastrointestinal illness associated with drinking well water delivered by tank truck during a period of drought--Nova Scotia. PMID- 1299431 TI - New licensure for another Haemophilus influenzae type B vaccine. PMID- 1299432 TI - A survey of invasive Haemophilus influenzae infections--England and Wales. AB - A survey of invasive H. influenzae infections has been underway in 6 regions of England and Wales since September 1990. In the first year, there were 433 cases of which 362 (84%) were due to H. influenzae type b (Hib). The majority of Hib infections were in children aged less than 5 years (annual incidence in this age group is 26.4/100,000). Meningitis occurred in 56% of cases of Hib infection. The results confirm previous evidence of the need to incorporate Hib vaccination into the childhood immunization schedule. The ongoing survey data will provide useful information to assess the impact of an Hib immunization program. PMID- 1299434 TI - [The late sequelae of the long-term stay of man under hyperbaric conditions]. PMID- 1299433 TI - [The characteristics of the extreme actions on the bodies of deep-sea divers during saturation dives and the basic task of medical support for these descents]. AB - A novel dive method, namely, saturation diving is presented. Extreme factors affecting the deep divers during such saturation dives are listed. The physiologic parameters of early adaptation, stable adaptation, early disadaptation and readaptation periods of a man during prolonged staying in a hyperbaric artificial gaseous environment are evaluated. The key task of medical monitoring of saturation dives is discussed. PMID- 1299435 TI - [The late sequelae of the systematic action of a complex of real diving factors on the pulmonary ventilatory function of deep-sea divers]. AB - Parameters which characterize lung volumes, absolute and relative flow rates, breathing reserve, were found unchanged with increasing age and record of active dive service, and in some deep-divers these parameters were growing up. This was disclosed due to comparative analysis of lung ventilatory function changes in divers through certain amount of years of professional occupation. At the same time a significant decrease in small to middle calibre bronchi patency was noted. In 30% of experienced deep-divers the mean maximal forced expiratory flow at 75% forced vital capacity (FEF75) decreased to 39% of predicted value at one-second forced expiratory volume (FEV1) being normal. Maximal expiratory flow at 50% forced vital capacity (FEF50) were in inferior normal limit (52% of predicted value). PMID- 1299436 TI - [The dynamics of functional heart volumes in the descents of divers to depths of up to 15 m]. AB - In an underwater environment at a depth up to 15 m the cardiodynamic parameters of resting and exercising man were recorded echocardiographically. Increased functional volumes of the heart and decreased ejection fraction (EF) have been noted. Underwater reactions of the cardiac functional volumes in response to exercise were characterized by: a maximum rise in systolic volume on exposure to low level loading; decreases of end diastolic and end systolic blood volumes; an elevation of EF lower than on the surface. With an increase in diving depth the functional reserves of the heart of exercising man are exhausted more rapidly. PMID- 1299437 TI - [The readaptation of the respiration, blood circulation and body oxygen regimen in aquanauts after saturation dives to depths of up to 450 m]. AB - Main trace posthyperbaric and postdecompression responses to respiration, circulation and oxygen profiles, dynamics of their reduction in 99 aquanauts at pressure of 46 kgs/cm2 (0.46 mPa) during 14-30 day period have been studied. The respiratory changes were found to be characterized by: ventilatory function disorders which followed the obstructive-restrictive pattern; discoordination of ventilation regulation and slowing down of respiratory gas transport through aerohematic barrier. The hemodynamic shifts have been manifested as cardiac rhythm instability, heart pump function followed by decreased cardiac contractions on exercise exposures. The economy and efficiency of body oxygen profiles in a respiration loop become lower than that in hemodynamic loop. The rate of the alveolar oxygen supply is decreased to the levels lower than the rates of oxygen supply by arterial and mixed venous blood. The long-term functional rearrangement of respiratory gas transport followed by the phase changes combined with the specific and nonspecific reactions persisting over a period of 30-60 days and more longer after decompression, is existed. PMID- 1299438 TI - [The effect of 2- and 3-component hyperbaric breathing mixtures on the self stimulation reaction and on the skeletal muscle electromyogram of rabbits]. AB - The effects of two- and three-component normoxic mixtures on self-stimulation and total bioelectrical activity of the skeletal muscles were evaluated in six test runs with 37 male rabbits. The increased partial pressures of He and N2 are found to affect differently intensity of self-stimulation which is enhanced in an O2-N2 environment and suppressed in that one consisting of He-O2. The He-N2-O2 mixture in which N2 amounts to 6% under pressure of 40 kgs/cm2 does not cause significant changes in self-stimulation as compared to that exposed by He-O2 breathing mixture. In contrast, trimix breathing (N2 amounts to 6%) under the same pressure did not result in an elevation in amplitude of muscular electric activity observed when used hyperbaric He-O2 breathing mixture. The experimental results may be indicative of an involvement of different mechanisms in genesis of the nervous syndrome of high pressure as well as of the fact that adding of N2 to He O2 mixture does not allow this pathologic state to be completely prevented. PMID- 1299439 TI - [Oxygen and hydrogen dynamics in the skin of aquanauts under a prolonged hyperbaric exposure]. AB - Polarographic measurements of the dynamics of partial pressures and diffusion parameters of O2 and H2 in the skin of aquanauts during prolonged hyperbaric exposure to He-O2 breathing to 3, 3.6 mPa were performed. It was indicated that at an early exposure stage there occur the distinct changes in cutaneous oxygen profiles manifested as: increased rate of local blood flow, decreased intensity of O2 utilization and due to this as elevated cutaneous PO2 levels. It is also noted that at the same exposure time an abrupt transient decline in diffusion rates of H2 and O2 through tissue and cell membrane of the skin of aquanauts is occurred. PMID- 1299440 TI - [The effect of the simulation of a prolonged dive to 100 m in a helium-oxygen environment on human erythrocytes]. AB - Three volunteers participated in the experiments to study the osmotic resistance and elemental composition of the erythrocytes during a 100-meter simulated saturation dive in He-O2 environment. The 15-day hyperbaric exposure resulted in a significant increase of erythrocytes resistance in response to a changed osmotic environment which was also maintained at an early stage of readaptation. The X-ray spectral local microanalysis revealed a decrease in chlorine, potassium and sodium level's on the 2nd postdecompression day. On a prolonged hyperbaric exposure at the expense of phospholipid exchange between plasma erythrocytes and lipoproteins, the erythrocyte membrane changes which may cause disturbances in ionic permeability of the cells are expected to occur. PMID- 1299441 TI - [The electrical and contractile responses during hyperbarism in the frog neuromuscular preparation]. AB - The well-known phenomenon of incrementing muscular contraction intensity induced by an increased ambient pressure is still unclear (P. Regnard, 1891). This study was done in order to establish whether an increased contraction intensity is the result of enhanced effect of triggering stimuli in response to pressure elevation to 100 atm or a rise in muscle contraction intensity depends on other reasons. When studying the nerve stimulation electric response (muscle action potential, MAP) at increased pressure, the MAP amplitude significantly decreased about two fold whereas the contraction intensity increased two-fold. The response duration was also elevated. Since electric stimulation was supramaximal in an intensity throughout the experiment the contraction-generating nervous impulse was sufficient for stimulating all the muscle fibers. No significant changes in other parameters of electric potentials occurring during neuromuscular transmission under pressure have been found which agrees with available neurophysiologic data. Thus, the causes responsible for an increased contraction intensity appear to depend on an altered muscle fiber contractility. This phenomenon provides the basis for understanding the changes in peripheric structures of the body and the periphery contribution to the genesis of hyperbaric nervous syndrome. PMID- 1299442 TI - [Water-salt metabolism and its hormonal regulation studied in the 2nd joint Soviet-French space flight]. AB - During a 25-day space mission of French cosmonaut on board Mir station, the joint Soviet-French Czecho-Slovak experiment "Minilab" has been conducted in order to evaluate a fluid-electrolyte metabolism status and its hormonal control at different flight stages and early postflight. In cosmonaut venous blood was drawn twice, and 24-hour urine samples were collected on mission Days 5 and 19. With the aid of Plasma-02 equipment the blood plasma and urinary samples were treated, frozen and maintained aboard the station. Postflight, frozen samples were delivered to the laboratory for further analyses. In-flight, urinary excretion of fluid and sodium decreased by 25-35%. On mission Day 9, the blood plasma levels of vasopressin increased by 450% and on Day 20 by 700% as opposed to the baseline levels, blood aldosterone content was also elevated with an increased renal excretion of both hormones. Blood plasma renin activity elevated two-fold, and atrio-natriuretic factor (ANF) content practically did not differ from a baseline value. In-flight circulating plasma volume (CPV) decreased by 20%. Postflight, there occurred the body hypohydration and activation of the hormonal systems providing a retention of body fluids and electrolytes to restore an adequate CPV and fluid-electrolyte homeostatic as a whole. PMID- 1299443 TI - [Cardiac bioelectrical activity in healthy men during 370-day head-down tilt hypokinesia]. AB - Nine men, aged 27-42 yrs, have been examined during a 370-day head-down tilt (HDT) experiment. The group A test subjects (4 persons) used the countermeasures involving exercises, pharmacological means to correct metabolism, bone tissue and digestive function. The group B test subjects (5 individuals) have embarked on exercising only in 120 days of bedrest. The electrocardiographic changes in the group A test subjects were insignificant, manifested mainly as a moderately decreased T-wave amplitudes in the most leads. In the group B test subjects at early HDT stages there was a negative dynamics: an elevated heart rate (HR) at rest, an increased time of atrioventricular transmission, decreased T-wave amplitudes followed in some cases by its widening and deformations. After the onset of physical training there appeared a tendency toward normalizing the values although T-wave amplitudes till terminating a bedrest period never reached baseline levels. In a rehabilitation period, both groups displayed the dynamics similarity: initially the HR lability and certain decrease in T-wave amplitudes were noted. By the end of 2nd month of rehabilitation the ECGs in all the test subjects of both groups practically normalized, but in Group B this process developed more slower. Thus, a year-long HDT experiment exerted a moderately adverse effect on myocardium metabolism and HR control mainly in the Group B test subjects. The observed changes are reversible and can be regarded as functional. PMID- 1299444 TI - [The hemodynamics and activity of the sympathetic-adrenal system in air traffic controllers during their professional duties]. AB - A functional status of the circulation and catecholamines excretion in air traffic controllers operating in two shifts (morning and daytime duties) and attending a Start air traffic control system have been assessed. It is shown that a correlations pattern between parameters under study is significantly altered depending on an occupational activity time. The dependence of hemodynamic shifts on an activity of hormonal and mediator components of sympathetic-adrenal system, an accomplishment of the catecholamine effects on cardiovascular activity with an involvement of alpha- and beta-adrenoreceptor system are shown. PMID- 1299445 TI - [Lipid peroxidation and the system of antioxidant protection in rats following a 13-day space flight on the Kosmos-1887 biosatellite]. AB - After a 13-day space mission, in the rats flown on Cosmos-1887 biosatellite the parameters of lipid peroxidation and antioxidant defense system--the contents of diene conjugates, malonic dialdehyde, Schiff bases, tocopherol, total antioxidant activity (in blood plasma only), antioxidant enzyme activity (in tissues only)- superoxide dismutase, catalase, glutathio peroxidase, glutathio reductase have been measured in the blood plasma, myocardium, skeletal muscles and liver. The liver level of diene conjugates, Schiff bases and tocopherol decreased, and an activity of superoxide dismutase and catalase increased. In the skeletal muscles there was an elevation of diene conjugate contents followed by the decreases in malonic dialdehyde and superoxide dismutase activity. In rat myocardium, superoxide dismutase activity and tocopherol levels increased significantly. In the blood plasma the levels of tocopherol, malonic dialdehyde and total antioxidant activity were elevated. It is concluded that the observed changes in lipid peroxidation developed probably in response to an effect of the last dynamic stage of space flight and during re-adapting to the Earth environments. PMID- 1299446 TI - [The spontaneous and evoked neuronal activity of the parietal associative cortex in cats during motion sickness]. AB - In the experiments with the cats a spontaneous and induced activity of the neurons (57) of parietal associated cortex during motion sickness was studied. It was found that after a 15 min motion sickness 54 percent of the examined neurons displayed suppression, 20 percent of neurons did an increase of spontaneous activity. Twenty-six percent of neurons did not respond to motion sickness. The dynamics of induced neuronal responses under motion sickness effect was complex, a direction of the changes in induced responses frequently did not agree with that of alterations in a spontaneous cellular activity. The more stable changes of induced responses have been in the neurons with phase responses to the fight and electrocutaneous stimulation. After 45-min effect of motion sickness, the light-stimulated responses were characterized by an increase of early and suppression of late components of a response, and the responses to electrocutaneous stimulation displayed mainly a suppression of the early components of the responses. PMID- 1299447 TI - [The hematological status of rats born and raised under increased gravitational force]. AB - Blood and bone marrow morphology of the rats the pre- and postnatal development of which up to the ages of 60 and 75 days took place under 2g environments induced by a continuous centrifuge rotation. The response to a reduced gravity was studied in 60-day-old rats on post-rotation days 2 and 15. Immediately post rotation, these animals exhibited: an intensified erythropoiesis resulting in an elevated erythroid cell counts, an activated eosinophilopoiesis and decreased level of neutrophilopoiesis. Return of the animals to a terrestrial environment during a 2-week period has caused a greater increase of erythroid production and the tendency toward normalizing granulocytopoiesis. In the 75-day-old rats developed under 2g, erythro- and granulocytopoiesis have tended to be recovered and bone marrow population of lymphoid and plasma cells was significantly decreased. The results point to the fact that hemopoiesis adaptation to an increased gravity during the studied period of time is not accomplished and this hematologic status depends on a changed status, of the controlling systems. PMID- 1299448 TI - [The comparative characteristics of the bone marrow cellular composition in rats after the prolonged continuous or interrupted action of a low geomagnetic field]. AB - Bone marrow cell composition in male Wistar rats exposed to long-term continuous (Run 1) or interrupted (Run 2) hypo-geomagnetic field (HGMF) with an attenuation coefficient of 172.5 generating in a permalloic chamber has been studied. When comparing the rat myelograms of the two test runs, a significant increase of lymphoid cell content, less pronounced during an interrupted exposure to HGMF by 10.1 and 6.5%, respectively, was noted. Analysis of myeloid cell response indicated that on a continuous exposure to HGMF the percentage of neutrophilic promyelocytes and myelocytes is somewhat declined. The levels of mature relating to stab and nuclear-segmental neutrophils in bone marrow during both modes of HGMF exposures practically remained unchanged. A certain decrease in cell fractions of erythroblastic shoot (chiefly at the cost of polychromatophilic normocytes), to a lesser extent manifested during an interrupted exposure to HGMF (by 5.8 and 2.4%, respectively) was noted. Long-term exposure of the animals to a weak terrestrial magnetic field causes a particular eosinophilia of bone marrow due to an increased fraction of mature eosinophils approximately similar on both HGMF profiles (by 2.1 and 2.0% respectively). On an interrupted HGMF exposure there was a significant myelogram elevation of the mast cell counts by 1.4%. PMID- 1299449 TI - [The characteristics of lipid ligand binding by serum albumin in athletes]. AB - The ability of serum albumin to bind lipids, fatty acids and products of their peroxidation was studied in well trained sportsmen during a competitive period. Detected quantitative and qualitative alterations point to a protein involvement in metabolic changes in an adaptation to work loads. PMID- 1299450 TI - [Evoked potentials of the human brain during prolonged fasting]. AB - Dynamics of the visual evoked potentials of human brain during a long-term alimentary starvation is studied. During a 14-day fasting in healthy male volunteers abrupt changes are found in an amplitude and shape of the evoked potentials in the site of occipital leads: increase of time and maximum amplitude of the response; level of residual murmur; duration and square of slow negative wave; integrated spectral densities (ISDs), ranged 0.1-1; 1-4 and 4-8 Hz; decrease of ISDs ranged 8-13 Hz. On a 14th day of food consumption, the measurements of all the evoke potential parameters are somewhat declined but significantly exceed the baseline levels. Also, fasting results in changing a pattern of spatial sequence of the evoked potentials: an increase of the mean values of response time in all the lead sites; a rise of maximum amplitude of response in occipital lead sites, and a slight statistically insignificant trend to a diminished amplitude of response in temporal lead sites. PMID- 1299451 TI - [A method and apparatus for the simultaneous recording of the pedigrees in a large number of yeast cells]. PMID- 1299452 TI - [Human biorhythms after travels between regions (exemplified by Novosibirsk Vladivostok flights)]. PMID- 1299453 TI - [The righting reaction in the free fall of rats after a flight on the Kosmos-936 biosatellite]. AB - The free fall turning over reaction has been studied in the weightless and centrifuged rats flown on board Cosmos 936. There occur particular changes of the reaction in the weightless rats after landing and its complete absence in eyes closed centrifuged rats. The possible mechanisms responsible for the observed alterations are discussed. PMID- 1299454 TI - Social support and stressful life events: age differences in their effects on health-related quality of life among the chronically ill. AB - There is substantial evidence of individual variation in health-related quality of life measures that is not accounted for by age or disease condition. An understanding of factors that determine good health is necessary for maintained function and improved quality of life. This study examines the extent to which social support and stressful life events were more or less beneficial for the long-term physical functioning and emotional well-being of 1,402 chronically ill patients. Analyses, conducted separately in three age groups, showed that social support was beneficial for health over time regardless of age. In addition, low levels of support were particularly damaging for the physical functioning of older patients. Stressful life events impacted differentially on health-related quality of life; relationship events had an immediate effect on well-being which diminished with time; financial events had an immediate negative effect on functioning and well-being which persisted over time for middle-aged patients; bereavement had a delayed impact on quality of life, with the youngest patients especially vulnerable to its negative effects; work-related events had both negative and positive effects, depending on age group. Results reinforce the importance of identifying and dealing with psychosocial problems among patients with chronic disease. PMID- 1299455 TI - Do the pictures influence scores on the Dartmouth COOP Charts? AB - OBJECTIVE: To determine the effect of illustrations on COOP Chart responses. STUDY DESIGN: Randomized split-half design of 177 patients discharged from a medical centre during a 3 month interval. Patient responses were obtained. However, there are benefits from the use of illustrations. Further research measures. Demographic characteristics and health status. RESULTS: No response differences were observed between patients who received COOP Chart illustrations and those who did not receive illustrations. CONCLUSION: Pictures do not appear to affect responses to COOP Charts. However there are benefits of the use of illustrations. Also, further research should be conducted with other patient populations and other COOP Charts before conclusive statements can be made regarding the use of illustrations with the COOP Charts. PMID- 1299456 TI - Does changing the heart mean changing personality? A retrospective inquiry on 47 heart transplant patients. AB - Heart transplantation is not simply a question of replacing an organ that no longer functions. The heart is often seen as source of love, emotions, and focus of personality traits. To gain insight into the problem of whether transplant patients themselves feel a change in personality after having received a donor heart, 47 patients who were transplanted over a period of 2 years in Vienna, Austria, were asked for an interview. Three groups of patients could be identified: 79% stated that their personality had not changed at all postoperatively. In this group, patients showed massive defense and denial reactions, mainly by rapidly changing the subject or making the question ridiculous. Fifteen per cent stated that their personality had indeed changed, but not because of the donor organ, but due to the life-threatening event. Six per cent (three patients) reported a distinct change of personality due to their new hearts. These incorporation fantasies forced them to change feelings and reactions and accept those of the donor. Verbatim statements of these heart transplant recipients show that there seem to be severe problems regarding graft incorporation, which are based on the age-old idea of the heart as a centre that houses feelings and forms the personality. PMID- 1299458 TI - A reformulation of quality of life for medical science. AB - Current quality of life measuring tools are suited for economic decision making, not to investigate causal processes which lead to patients making evaluations of their lives. An alternative approach is presented based on research into positive versus negative life-satisfaction. Quality of life is a causal sequence of psychological states where perceived symptoms cause problems and the problems and symptoms cause evaluations, and where the causal sequence is a complex interaction between morbidity and psychological factors. Different types of medical intervention affect different stages in the causal sequence and so different types of quality of life instrument are needed for different kinds of medical research. PMID- 1299457 TI - Reliability and validity of a health-related quality of life battery for evaluating outpatient antidepressant treatment. AB - This study was designed to evaluate the reproducibility, validity and responsiveness of a health-related quality of life (HRQOL) battery that was assembled for the evaluation of antidepressant therapy. The Montgomery-Asberg Depression Rating Scale was used to measure severity of depression. The HRQOL battery contained measures of energy and fatigue, social behaviour, cognitive function, home and work role function, and general well-being (i.e., health perceptions, life satisfaction) selected from previously developed and validated instruments. The clinical investigators and research nurses reported on difficulty in using the HRQOL battery. Most patients were able to complete the questionnaire without problems within 10 min. Reproducibility was very good with intraclass correlation coefficients ranging from 0.74 to 0.97. The HRQOL scales showed evidence of good concurrent validity. The scales were moderately correlated with MADRS scores (r = 0.30-0.62). The magnitude of these correlations indicate that HRQOL scales are related to depression measures, but they are not alternative measures of depression. Changes in MADRS scores were associated with changes in all scales, except for work behaviour, indicating that improvements in depression ratings also resulted in improvements in health status and well-being. The HRQOL scales included in this study were found to be reliable, reproducible, and valid and no appreciable burden was placed on patients or investigators participating in the study. With the exception of the Work Behaviour scale, the HRQOL scales were very responsive to changes in depression severity. This brief HRQOL instrument can provide a comprehensive assessment of the outcomes of antidepressant treatment. PMID- 1299459 TI - Quality of life research and the ethics of evidence. PMID- 1299460 TI - Measurement of quality of life in patients: psychometric analyses of the Functional Living Index-Cancer (FLIC). AB - Biomedical advances in medical care and treatment have highlighted potential trade-offs between the length and quality of a patient's life. There is increasing need for psychometrically sound measurement of quality of life in medical patients. Psychometric analyses of the Functional Living Index-Cancer (FLIC) were conducted on data from 530 consecutive patients with histologically confirmed cancer. To examine construct validity, a principal components analysis was conducted that revealed a five-factor solution accounting for 70% of the variance in a random half of the original sample and 68% in a cross-replication sample. Content analysis indicated that domains of physical, psychological and social functioning are assessed along with the patient's view of their current well-being and disease symptoms. Convergent-discriminant validity was shown with independent measures of symptoms and anxiety. Most, but not all expected differences in quality of life by demographic and psychological variables were found. Within the limitations imposed by the study and its sample, the FLIC appears to be a conceptually sound, internally consistent instrument worthy of use and further study in other health care samples. PMID- 1299461 TI - Change and status in quality of life in patients with rheumatoid arthritis. AB - Current status in quality of life and deterioration retrospectively attributed to the disease by patients with rheumatoid arthritis (RA) were examined. The study group included 169 female and 53 male patients with probable (n = 70), definite (n = 127) and classical RA (n = 25). In a cross-sectional postal survey the participants self-rated their quality of life according to a generic self assessment package tailored in part for this study. Shortened parallel ratings by significant others were also performed. The impact of RA on quality of life was pervasive. Heaviest intrusion emerged within the physical life sphere and the behavioural and activity domain, followed by the impact on global life satisfaction and habits. Material, psychological and social life domains were less disrupted. In spite of the pervasive discomfort attributed to the illness, quality of life status was mostly rated as being 'rather good' to 'good'. There was a consistent pattern: the better off currently, the less disturbance from the disease perceived. Higher age and longer duration of RA were significantly correlated to a lower status. In addition, individuals still working rated a higher quality of life and less intrusion of the disease. Self-ratings were corroborated by ratings of significant others. While there was an agreement on the level of the negative impact of the disease, the patients rated their current situation more positively than did significant others. The dual assessment of quality of life status and change appears reasonable and informative as regards rheumatoid arthritis. PMID- 1299462 TI - Psychosocial problems of donor heart recipients adversely affecting quality of life. AB - Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them. PMID- 1299463 TI - The distinction between affect and cognition in the quality of life of cancer patients--sensitivity and stability. AB - The distinction between affect and cognition has been put forward to clarify the lack of differences found in studies describing quality of life under deteriorated circumstances, such as serious illness. In the study reported here, cancer patients under treatment (n = 201) were compared with a random sample from the normal population (n = 200). As hypothesized, the affective component of life quality turned out to be more severely impaired than the cognitive component. Besides, it was investigated which factors contribute to the affective and the cognitive component of the quality of life of cancer patients under treatment. In cancer patients affect proved more strongly related to the physical domain. Cognition on the other hand was more strongly related to coping resources, especially personality characteristics like the level of self-esteem. It is concluded that an affective measure of quality of life is more sensitive to change in patients. The stability of life quality is attributed to the rather strong relation the affective and the cognitive component both have to coping resources. PMID- 1299464 TI - Quality of life and psychosocial status in stage D prostate cancer. Zoladex Prostate Cancer Study Group. AB - Inasmuch as treatments for advanced prostate cancer may have identical clinical outcomes but very different meanings to patients, we sought to compare the impact of surgical and medical castration (orchiectomy versus injected goserelin acetate Zoladex) on quality of life and psychosocial status. A total of 147 men with Stage D prostate cancer participated in the study: 115 selected treatment with goserelin acetate, and 32 chose orchiectomy. Quality of life, as measured by the Functional Living Index: Cancer (FLIC), improved at both the 3 and the 6 month follow-up in the goserelin acetate group (p = 0.0001), but did not change from baseline at 6 months in the orchiectomy group (p = 0.54). These findings were paralleled by improvement from baseline in psychosocial status, as measured by the Profile of Mood States (POMS), at 6 month follow-up (p = 0.01 in the goserelin acetate group versus p = 0.60 in the orchiectomy group). This investigation, which is among the first to evaluate patients' appraisals of their lives following treatment choices for advanced prostatic cancer, argues compellingly for including quality of life in assessments of therapy. PMID- 1299465 TI - Quality of life consequences of chemotherapy-induced emesis. AB - Nausea and vomiting following chemotherapy administration are common and often overlooked causes of impairment in cancer patients. The goal of this study was to explore the broad range of consequences associated with this specific acute toxicity of chemotherapy. Specific objectives were: (1) create and test scales specifically designed to assess the impact of chemotherapy-induced nausea and vomiting or patients' daily function; (2) examine changes in quality of life of cancer patients 3 days following chemotherapy administration; (3) assess the impact of chemotherapy-induced emesis on quality of life and patients' daily function; (4) identify medical and non-medical cost-related consequences associated with chemotherapy-induced emesis. Patients receiving intermittent bolus chemotherapy regimens on an outpatient basis were eligible for this survey. Four instruments were used: a patient maintained diary, the Functional Living Index-Cancer (FLIC), a newly created Functional Living Index-Emesis (FLIE) and an Item Check list for cost-related consequences. On Day 1, before chemotherapy, patients completed the FLIC and FLIE. Patients recorded episodes on vomiting, severity of nausea, anxiety, sedation, antiemetics self-administered, and adverse effects in diaries for 3 days following chemotherapy. The FLIC and FLIE were completed at the end of Day 3. The Item Check list of cost-related consequences was administered as a telephone survey on Day 5. Approximately 56% of 122 patients reported chemotherapy-induced emesis (CIE). A change in mean FLIC score indicating a decline in quality of life was observed for the CIE group (119 to 101) but not in the group who did not report emesis (124 to 122). Decline in FLIC and FLIE from before to after chemotherapy administration was greater for CIE patients (p = 0.001). FLIE scores indicated that CIE patients perceived that vomiting, and to a slightly lesser extent, nausea substantively influenced their ability to complete household tasks, enjoy meals, spend time with family and friends, and maintain daily function and recreation. Effect size calculations supported a significant negative relationship between occurrence of CIE and the direction and magnitude of functional living index change. An exploratory analysis (principal component followed by regression analysis) supported the hypothesis that side-effects produced by chemotherapy and antiemetic therapy significantly contributed to changes in quality of life observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1299467 TI - International Quality of Life Assessment (IQOLA) Project. AB - The International Quality of Life Assessment (IQOLA) Project is a 4-year project to translate and adapt the widely used MOS SF-36 Health Survey Questionnaire in up to 15 countries and validate, norm, and document the new translations as required for their use in international studies of health outcomes. In addition to the eight-scale SF-36 health profile, the project will also validate psychometrically based physical and mental health summary scores, as well as health utility indexes incorporating SF-36 scales for use in cost-utility studies. PMID- 1299466 TI - Nursing research into quality of life. AB - This report describes the scope of nursing research in the area of quality of life. The strategy used to identify research reports relied heavily on nursing publications included in the Cumulative Index for Nursing and Allied Health Literature (CINAHL) from 1983 (when the database first included the subject, quality of life) to December, 1991. During this period, over 1,000 references concerning quality of life can be identified through a key-word search of the data set. Nursing investigators defined quality of life in terms of psychological, physical, social/interpersonal, and financial/material well-being. Nursing instruments have been developed to measure one or more of these dimensions of the concept. Nursing journals like Advances in Nursing Science (1985), Seminars in Oncology Nursing (1990), and Progress in Cardiovascular Nursing (1992) dedicated whole issues to the topic. Major nursing associations have supported conferences/talks (American Heart Association Council on Cardiovascular Nursing, Santa Fe, NM, 1991; Oncology Nursing Society, Fall Institute, Annual Quality of Life Lectureship) and provided awards on the subject (Oncology Nursing Society Annual Quality of Life Research Award). The National Center for Nursing Research is launching an intramural programme to address quality of life questions. PMID- 1299468 TI - Changes in quality of life among persons with HIV infection. AB - Health-related quality of life (QOL) is an important component of the evaluation of patient outcome in HIV infection where disease is progressive and debilitating. This paper compares patient-reported QOL obtained from questionnaires which cover functional ability, social functioning, cognition, mental health, disability days, disease symptoms, and overall health in the previous 3 months. These scales have been validated on HIV populations. We compared changes in health status over 12 months for 669 patients with varying HIV disease severity: 134 asymptomatic, 416 symptomatic (previously termed ARC), and 119 AIDS. Groups were evaluated at baseline for demographic and health status differences (i.e., age, CD4+). Declines in health status and psychosocial status were found over the year for all persons. Individuals with symptomatic disease or AIDS had significant declines of 10-20% (p < 0.001) in all aspects of role functioning (social, daily activities, energy, and global health) and increased disease symptoms, but no significant declines in cognition or mental health. Persons with AIDS had greater declines than those with symptomatic disease. AIDS and symptomatic patients also reported significantly fewer hours at work and more disability days than asymptomatic patients. The impact that HIV disease has on the health status of non-AIDS symptomatic patients is especially striking. PMID- 1299469 TI - Assessment of quality of life in the elderly assisted at home through a Tele Check service. AB - This study evaluates the effects of a Tele-check/Tele-emergency service on the quality of life in the elderly. Through telephone interviews a questionnaire has been repeatedly administered to explore various psychological, somatic, and social aspects in a random sample of 574 subjects aged 65 years and over (mean = 76.8 years). The findings suggest that the elderly helped by the service (in its 'control' functioning) make less demands on health facilities (GPs visits, number of days in hospital) as compared to controls. Implications are presented and discussed. PMID- 1299470 TI - Measurement of quality of life in bone marrow transplantation survivors. AB - This study was designed to assess the reliability and validity of a Quality of Life (QOL) instrument on a sample of 179 allogeneic Bone Marrow Transplant (BMT) survivors. The QOL-BMT tool was developed specifically for this population and was based on the investigators' prior research and a conceptual model of Quality of Life. Patients who were at least 100 days post BMT completed the 30 item visual analogue questionnaire. The instrument measured physical symptoms (e.g., weight loss, frequent colds, skin changes, cataracts, sexual problems), psychological symptoms (e.g., worry about recurrence, adjustment to illness), social concerns (e.g., relationship adjustment, return to work), and spiritual well-being (e.g., sense of control, future goals). Psychometric analysis of the instrument included measures of reliability and validity. The study findings demonstrate the unique aspects of QOL dimensions in BMT survivors and the value of QOL assessment in clinical practice and research. PMID- 1299471 TI - The SmithKline Beecham 'quality of life' scale: a validation and reliability study in patients with affective disorder. AB - The rationale for the development of Repertory-Grid based quality of life assessment (QOL) is described. The emergent scale, the SmithKline Beecham Quality of Life Scale (SBQOL) utilizes 23 predetermined constructs and three fixed elements: self now, ideal self and sick self. Inclusion of the latter two elements provides a personal frame of reference for the individual and recognizes the highly idiosyncratic and subjective nature of the experience which constitutes quality of life. A study of the validity and reliability of the SBQOL was conducted in 129 patients presenting to their GP with either major depression or generalized anxiety disorder, as defined by DSM III R. Patients were treated at the discretion of their GP and followed over a period of 12 weeks with assessments of treatment efficacy being performed at 6 weeks and 12 weeks in parallel with administration of the SBQOL. The results from co-administration of standard efficacy measures such as the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA) with the SBQOL, provided good evidence of construct validity. Evidence in support of the concurrent validity of the SBQOL was provided by co-administration of the Sickness Impact Profile and General Health Questionnaire (external criteria) with the SBQOL scale. Test-retest reliability and internal consistency were high. No obvious advantage was conferred by the use of principal components analysis from the Flexigrid software package in contrast to a simple arithmetical procedure for computing interelement distances. It is concluded that the SBQOL provides a valid, reliable and practicable approach to the assessment of quality of life in patients with affective disorder. PMID- 1299473 TI - The administrative challenges in ambulatory surgery. PMID- 1299474 TI - Crossroads in ambulatory surgery. AB - In its short history, same-day surgery has encountered several major decision points or crossroads: during its inception, and when facing the decision to expand to meet the needs of radiology, cardiology, and neurology. Changes in surgery toward less invasive procedures, such as laparoscopic, laser, and stapling procedures influence institutions to make major decisions involving same day surgery. Perioperative nurses in ambulatory services are being compelled to look at efficiencies regarding patient contact and interaction. Major decisions regarding these nursing approaches must be made, just as major decisions have been required in ambulatory services in the past. PMID- 1299472 TI - Assessing the needs and quality of life of patients with HIV infection: development of the HIV Overview of Problems-Evaluation System (HOPES). AB - OBJECTIVE: To develop and evaluate the psychometric properties (reliability, validity etc.) of a comprehensive Quality of Life (QOL) tool, for patients infected with the human immunodeficiency virus (HIV), that was adapted from a previously validated cancer tool. DESIGN: Cross-sectional, patient completed written surveys and interviews. SETTING: The Medical Centers serving HIV infected patients in the Los Angeles community including UCLA, community physicians, Veterans Affairs Medical Centers, and a County hospital: and additional data contributed from Johns Hopkins University Medical Center CMV Retinitis Clinic. PATIENTS: Patients (n = 318) with HIV infection including asymptomatic (37%), ARC (20%), AIDS (25%) and AIDS with Cancer (18%) receiving health services at one of the above sites. MEASUREMENTS: The patients self-administered the newly developed instrument, the HOPES (HIV Overview of Problems-Evaluation System), other QOL related tools including the Medical Outcomes Study instrument adapted for HIV (MOS-HIV) the Profile of Mood States (POMS), the Perceived Adjustment to Chronic Illness Scale (PACIS), and the Physical Activity Scale (PAS). Brief interview to assess the Karnofsky Performance Status Score (KPS). Measured sociodemographic characteristics included age, sex, race, HIV risk factor, education etc. Assessed medical history, current medications, HIV clinical classification. MAIN RESULTS: The sociodemographic and medical characteristics of the sample resemble those of the general population with HIV infection in this geographic area: 96% male, 28% nonwhite, 84% homosexual contact as risk factor, 75% receiving antiretroviral therapy. The adaptation of the cancer QOL instrument to HIV appears to have face and content validity according to patients and health professionals who care for HIV infected patients. Analyses of the psychometric properties found that the HOPES has a similar structure to its parent instrument following factor analyses which results in five summary scales representing the Physical, Psychosocial, Medical Interaction, Sexual and Significant Other/Partners domains in addition to a Global Score. Internal consistency of 35 subscales is high with a mean alpha coefficient of 0.82. Correlations of the HOPES summary scales with other QOL instruments are in the predicted directions. Comparing patients within the HIV clinical diagnostic categories on the HOPES Global, Physical, and Psychosocial Summary Scales indicates that Asymptomatic Patients have better QOL than symptomatic patients. This finding is also found in the other QOL instruments which provides evidence of construct validity. CONCLUSIONS: The HOPES is an excellent tool for identifying the problems and needs of patients with HIV infection and for assessing their quality of life. It is reliable, valid and acceptable to patients. The tool may be especially useful in developing a normative data base. PMID- 1299475 TI - Development of a freestanding health care facility. AB - The development of a freestanding ambulatory health care facility requires careful planning by the investors before starting the project. A corporate strategic plan should be developed well in advance of hiring a developer or acquiring property for the facility. This strategic plan will serve as a guide for all activities involved in the development and opening of the facility. PMID- 1299476 TI - Integrated preadmission services and case management: the foundation for achievable patient outcomes in a hospital-based ambulatory surgery setting. AB - The forces of technology and changing payor requirements continue to move many surgical procedures to the ambulatory setting. The American Hospital Association's Hospital Statistics, 1991-92 indicates that more than half of all surgeries are now performed on an ambulatory or outpatient basis. Hospital-based ambulatory surgery programs must learn to fully integrate many of their traditional inpatient hospital services with the needs of the ambulatory surgery patient by developing preadmission services, as well as by adopting case management theory to continue to deliver quality ambulatory care. PMID- 1299477 TI - Staff selection for an ambulatory surgery unit. AB - Major changes in the care delivery system affect the selection of the professional nursing staff for an ambulatory surgery unit. The skills required are diverse and dynamic. Selecting the right applicant requires not only knowledge of the interview process, but also acute observation and communication skills. The use of a matrix system helps to organize the process as well as to quantify and qualify the information gained. PMID- 1299478 TI - Cross-training: a staffing alternative in ambulatory surgery. AB - Content plateauing, which occurs when one's work becomes too routine, may be prevented by the cross-training and cross-utilization of staff. This article tracks the process of cross-training and cross-utilization from its inception at Lutheran Medical Center in Denver, Colorado. PMID- 1299479 TI - Managing quality and reducing risks in ambulatory surgery. AB - This article reviews the evolution of quality assurance and continuous quality improvement (QA/CQI) in ambulatory surgery centers. As an example, The QA/CQI Plan of the Gumenick Ambulatory Care Center is examined in detail. PMID- 1299480 TI - Marketing ambulatory services in the 1990s. AB - The ability to predict, to adapt to change, and to develop strategic low cost marketing plans are the components essential to remaining financially solvent in today's health care environment. The marketing process is analogous to the nursing process and should support the institution's mission statement, philosophy, and goals. Managers who are able to empower their personnel to become the sales force and implement the marketing plan will be the survivors in the 1990s. PMID- 1299481 TI - Implementing standards of perioperative clinical practice in the ambulatory surgery setting. PMID- 1299482 TI - Influence of diet and exercise on energy expenditure--a review. AB - Maintenance of a healthy body weight results from equating total energy intake to total energy expenditure (resting metabolic rate, RMR; the thermic effect of feeding, TEF; the thermic effect of activity, TEA; and adaptive thermogenesis, AT). Dietary quantity and composition and acute and chronic exercise have been shown to influence all components of total energy expenditure. This paper reviews the effects of exercise and diet on energy expenditure and, ultimately, energy balance. Overnutrition increases RMR and TEF while undernutrition decreases them. Carbohydrate and protein oxidation is closely tied to intake whereas fat oxidation does not closely parallel fat intake. Thus excess fat intake is likely to lead to fat storage. Acute endurance exercise at > 70% VO2max increases postexercise RMR and TEF. Chronic exercise training may increase RMR while also increasing TEF. Review of the research indicates that energy balance may best be achieved by consuming an energy appropriate, low fat diet complemented by endurance exercise. PMID- 1299483 TI - Effects of phosphate loading on metabolic and myocardial responses to maximal and endurance exercise. AB - Six trained male cyclists and triathletes participated in a double blind study to determine the effects of phosphate loading on maximal and endurance exercise performance. Subjects ingested either 1 gm of tribasic sodium phosphate or a glucose placebo four times daily for 3 days prior to performing either an incremental maximal cycling test or a simulated 40-km time trial on a computerized race simulator. They continued the supplementation protocol for an additional day and then performed the remaining maximal or performance exercise test. Subjects observed a 17-day washout period between testing sessions and repeated the experiment with the alternate supplement regimen in identical fashion. Metabolic data were collected at 15-sec intervals while venous blood samples and 2D-echocardiographic data were collected during each stage of exercise during the maximal exercise test and at 8-km intervals during the 40-km time trial. Results indicate that phosphate loading attenuated anaerobic threshold, increased myocardial ejection fraction and fractional shortening, increased maximal oxidative capacity, and enhanced endurance performance in competitive cyclists and triathletes. PMID- 1299484 TI - Comparison of four methods to assess body composition in black and white athletes. AB - Four methods of assessing body composition were compared in 55 black and 35 white, Division I, American football players. Percent body fat (%BF) was estimated with hydrostatic weighing at residual volume, corrected for race; seven site skinfolds (7 SF), corrected for race; bioelectrical impedance analysis (BIA); and near-infrared spectrophotometry (NIR). Percent body fat with HW in blacks (mean = 14.7%) and whites (19.7%) did not differ (P > .05) from %BF with 7 SF (blacks, 14.7%; whites, 19.0%). In relation to HW, BIA significantly (P < .05) overpredicted (blacks: 20.1%, SEE = 3.2%; whites: 22.3%, SEE = 4.3%) and NIR underpredicted %BF (blacks: 12.6%, SEE = 3.9%; whites: 17.7%, SEE = 3.6%). The contribution of BIA variables (resistance, phase angle, conductance) and NIR optical density to predict %BF was trivial compared to body mass index. It appears that race may not substantially influence %BF prediction by NIR and BIA. It was concluded that when considering the cost and expertise required with NIR and BIA, SF measurements appear to be a superior alternative for rapid and accurate body composition assessment of athletes, independent of race. PMID- 1299485 TI - Predictive accuracy of three field methods for estimating relative body fatness of nonobese and obese women. AB - Three methods of body composition assessment were used to estimate percent body fat (%BF) in nonobese (n = 77) and obese (n = 71) women, 20-72 yrs of age. Skinfolds (SKF), bioelectrical impedance (BIA), and near-infrared interactance (NIR) methods were compared to criterion-derived %BF from hydrostatic weighing (%BFHW). Nonobese subjects had < 30% BFHW and obese subjects had > or = 30% BFHW. The Jackson, Pollock, and Ward SKF equation and the manufacturer's equations for BIA (Valhalla) and NIR (Futrex-5000) were used. For nonobese women there were no significant differences between mean %BFHW and %BFSKF, %BFBIA, and %BFNIR. The rs and SEEs were 0.65 and 3.4% BF for SKF, 0.61 and 3.6% BF for BIA, and 0.58 and 3.7% BF for NIR for nonobese subjects. For obese women, mean %BFHW was significantly underestimated by the SKF, BIA, and NIR methods. The rs and SEEs for the obese group were 0.59 and 3.4% BF for SKF, 0.56 and 3.5% BF for BIA, and 0.36 and 3.9% BF for NIR. The total errors of the equations ranged from 5.6 to 8.0% BF in the obese group. It is concluded that all three field methods accurately estimate %BF for nonobese women; however, none of the methods is suitable for estimating %BF for obese women. PMID- 1299486 TI - Exercise intensity and the thermic effect of food. AB - This study investigated the effect of varying exercise intensity on the thermic effect of food (TEF). Sixteen lean male subjects were matched for VO2 max and randomly assigned to either a high or low intensity group for 30 min of treadmill exercise. Caloric expenditure was measured using indirect calorimetry at rest and at 30-min intervals over 3 hrs following each of three conditions: a 750-kcal liquid meal, high or low intensity exercise, and a 750-kcal liquid meal followed by high or low intensity exercise. Low intensity exercise enhanced the TEF during recovery at 60 and 90 min while high intensity enhanced it only at 180 min but depressed it at 30 min. Total metabolic expense for a 3-hr postmeal period was not differently affected by the two exercise intensities. Exercise following a meal had a synergistic effect on metabolism; however, this effect was delayed until 180 min postmeal when exercise intensity was high. The circulatory demands of high intensity exercise may have initially blunted the TEF, but ultimately the TEF measured over the 3-hr period was at least equal to that experienced following low intensity exercise. PMID- 1299487 TI - Efficacy of chromium supplementation in athletes: emphasis on anabolism. AB - As the biologically active component of glucose tolerance factor (GTF), the essential trace mineral chromium is now being marked to athletes. GTF potentiates insulin activity and is responsible for normal insulin function. Thus, insulin's effects on carbohydrate, fat, and protein metabolism are dependent upon the maintenance of adequate chromium stores. Due to excessive chromium loss and marginal chromium intake, athletes may have an increased requirement for chromium. Therefore, in some circumstances the dietary supplementation of a chromium compound may be efficacious. The restoration and maintenance of chromium stores via supplementation would promote optimal insulin efficiency, necessary for high-level athletic performance. However, potential anabolic effects of enhanced insulin function would likely be marginal, and reports of short-term anabolic increases from the supplementation of an organic chromium compound need to be confirmed. PMID- 1299488 TI - The effect of 7 to 8 months of vitamin/mineral supplementation on the vitamin and mineral status of athletes. AB - Blood indicators of eight vitamins (B1, B2, B6, C, E, A, B12, folate) and six minerals (Cu, Mg, Zn, Ca, P, Al) were measured in 86 athletes before and after a 7- to 8-month period of training. During this period half consumed a multivitamin/mineral supplement and a matched group took a placebo. Following the supplementation period, blood biochemical indicators of B1, B6, B12, and folate status all increased but there were no significant effects of supplementation on B2, C, E, and A, or on the blood levels of any of the minerals. The supplementation had no effect on red or white cell counts or on hemoglobin levels. Irrespective of the supplementation, some blood measures varied according to sex, females evidencing significantly higher values than males for vitamins C, E, copper, magnesium, and aluminium, with B2 being higher in males. It is concluded that 7 to 8 months of multivitamin/mineral supplementation increased the blood nutritional status of some vitamins but did not affect any blood mineral levels, and that some blood nutritional indicators may vary according to sex. PMID- 1299489 TI - The effect of 7 to 8 months of vitamin/mineral supplementation on athletic performance. AB - The effect of vitamin and mineral supplementation was studied over 7 to 8 months of training and competition in 82 athletes from four sports: basketball, gymnastics, rowing, and swimming. Matched subgroups were formed and a double blind design used, with subgroups being given either the supplementation or a placebo. All athletes were monitored to ensure that the recommended daily intakes (RDI) of vitamins and minerals were provided by diet alone. Sport-specific and some common tests of strength as well as aerobic and anaerobic fitness were performed. Coaches' assessment of improvement was also obtained. The only significant effect of supplementation was observed in the female basketball players, in which the supplementation was associated with increased body weight, skinfold sum, and jumping ability. A significant increase in skinfold sum was also demonstrated over the whole group as a result of supplementation. In general, however, this study provided little evidence of any effect of supplementation to athletic performance for athletes consuming the dietary RDIs. PMID- 1299490 TI - Failure of magnesium supplementation to influence marathon running performance or recovery in magnesium-replete subjects. AB - This study examined the effect of magnesium supplementation on muscle magnesium content, on running performance during a 42-km marathon footrace, and on muscle damage and the rate of recovery of muscle function following the race. Twenty athletes were divided equally into two matched groups and were studied for 4 weeks before and 6 weeks after a marathon in a double-blind trial; the experimental group received magnesium supplement (365 mg per day) and the control group, placebo. Magnesium supplementation did not increase either muscle or serum magnesium concentrations and had no measurable effect on 42-km marathon running performance. Extra magnesium ingestion also had no influence on the extent of muscle damage or the rate of recovery of muscle function. The latter was significantly reduced immediately after the marathon but returned to normal within 1 week. Thus, magnesium supplementation in magnesium-replete subjects did not enhance performance or increase resistance to muscle damage during the race, or the rate of recovery of muscle function following the race. PMID- 1299491 TI - Does calcium supplementation prevent bone stress injuries? A clinical trial. AB - This study investigated the effect of calcium supplementation in preventing bone stress injuries. Healthy male military recruits (N = 1,398) served as subjects, of which 247 were randomly allocated to an experimental group (E) while 1,151 served as a control group (C). For 9 weeks both groups wore the same footwear and had the same physical training program. The baseline dietary intake of calcium in 50 randomly selected subjects of each group was assessed using a 24-hr dietary record. The E group received a daily calcium supplement while the C group did not. Injuries were monitored in all subjects by a panel of doctors who followed specific diagnostic criteria. The mean weekly injury incidence for all overuse injuries, but specifically tibial stress syndrome and stress fractures, was similar in both groups. Mean baseline daily dietary calcium intake was above 800 mg in both subgroups. This study demonstrated that large-scale calcium supplementation (500 mg/day) beyond usual dietary intake did not influence the risk of developing bone stress injuries during a 9-wk physical training program in these young military recruits. PMID- 1299492 TI - Changes in plasma zinc following high force eccentric exercise. AB - This study was done to determine whether eccentric exercise that causes muscle damage will produce an increase in plasma levels of zinc. Changes in total plasma zinc concentration (Zn) were examined following an eccentric and concentric exercise of the forearm flexors. Eight female subjects performed 24 maximal concentric actions (CON) with one arm and 10-14 days later performed 24 maximal eccentric actions (ECC) with the other arm. Maximal isometric force, elbow joint angles at a relaxed (RANG) and flexed position (FANG), muscle soreness, and plasma creatine kinase activity (CK) were measured as indicators of muscle damage. Zn levels were determined at the same time as CK. Maximal isometric force, RANG, FANG, and muscle soreness showed large changes after ECC but little if any change after CON. CK increased significantly after ECC but did not change after CON. Neither ECC nor CON showed significant changes in Zn following exercise. It is concluded that exercise-induced muscle damage does not appear to produce an increase in plasma zinc levels. PMID- 1299493 TI - Nutritional ergogenic aids: carnitine. PMID- 1299494 TI - The hyponatremia of exercise. AB - The hyponatremia of exercise may exist in symptomatic and asymptomatic forms. Symptomatic hyponatremia is usually characterized by severe alterations in cerebral function including coma and grand mal seizures; it develops especially in less competitive athletes who have maintained high rates of fluid intake during endurance events lasting at least 5 hours. The hyponatremia becomes symptomatic when the volume of excess fluid retained exceeds 2 to 3 liters. The etiology of the condition is unknown. Possibly as many as three or more pathologies (abnormal fluid retention possibly due to inappropriate ADH secretion, abnormal regulation of the extracellular fluid volume, translocation of sodium into a "third space") must be present for symptomatic hyponatremia to develop. The avoidance of overhydration would appear to be the only certain way that susceptible individuals can prevent symptomatic hyponatremia. Sodium chloride containing solutions ingested in physiologically significant concentrations would likely prevent a possible "third space" effect. PMID- 1299495 TI - Rationale for upper limits of electrolyte replacement during exercise. AB - The addition of carbohydrate and sodium to sport drinks has been recommended to enhance fluid intake and absorption and to delay fatigue. Other electrolytes (E) which are lost through sweating are also commonly added. However, too many E may lead to increased serum E and osmolality levels, which may negatively influence thermoregulation, depress sweating, and cause gastrointestinal distress. On the other hand, drinking large amounts of plain water to compensate sweat loss may induce hyponatremia. Therefore, literature describing sweat E losses was examined in order to estimate average whole-body E loss and to determine an upper limit for replacement of E with sport drinks. Mean E loss was determined from 13 studies, with +/- 1 SD resulting in a hypothetical range for E losses. Correction for net absorption resulted in an upper limit fo electrolyte replacement. It is suggested that the E levels in sport rehydration drinks should not exceed the upper limit of the range given. PMID- 1299496 TI - The effects of a carbonated carbohydrate drink on gastric emptying, gastrointestinal distress, and exercise performance. AB - To determine the effect of a carbonated carbohydrate (CHO) drink on gastric function and exercise performance, eight male cyclists completed four 120-min bouts of cycling. Each bout consisted of a 105-min ride at 70% VO2max followed by a 15-min self-paced performance ride. During each trial, one of four test solutions was ingested: carbonated CHO (C-10%), noncarbonated CHO (NC-10%), carbonated non-CHO (C), and noncarbonated non-CHO (NC). Following the performance ride, the subjects had their stomach contents removed by aspiration. There were no significant differences in gastric emptying (GE) except for Trial C-10%, which averaged 13.3% less than NC. However, there was no difference in the perception of gastrointestinal comfort between this trial and any other. Average power output during the performance ride was not significantly different between carbonated and noncarbonated trials, or between CHO-fed and no-CHO trials; however, the subjects worked at a greater intensity when fed CHO. Finally, acid base status did not change when a carbonated drink was ingested. This indicates that adding carbonation to a sport drink does not significantly alter gastric function, the perception of GI comfort, or exercise performance. PMID- 1299497 TI - Effects of downhill running on the responses to an oral glucose challenge. AB - Because muscle damage from eccentric exercise has been associated with alterations in muscle glycogen metabolism, this study determined the effects of exercise on the insulin and glucose responses to an oral glucose tolerance test (OGTT). In a repeated-measures design, 11 subjects undertook either no exercise, 2 min of isokinetic leg exercise, or 50 min of level or downhill running. No exercise was performed and diet was controlled during the 48 hrs after the treatments and before the OGTT. Ratings of muscle soreness and CK activity were significantly elevated 48 hrs after downhill running. Level running also increased CK activity but did not induce muscle soreness. Isokinetic exercise did not affect either one. Blood glucose responses to the OGTT were similar among the treatments. In contrast, the insulin responses to the OGTT following downhill running were significantly increased. These results suggest that eccentric exercise associated with downhill running that results in delayed muscle soreness is associated with the development of a mild insulin-resistant condition. PMID- 1299498 TI - Vitamin C intake and lipid profiles of competitive male and female bodybuilders. AB - This research compared nutrient intake data with blood lipids and anthropometric data. Height, weight, and seven skinfolds were collected 3 days prior to competition at the official weigh-in. The lipids measured were total cholesterol (TC), HDL-cholesterol (HDL-C), and the HDL2 and HDL3 cholesterol subfractions. The subjects were 17 males and 17 females. Descriptive data are presented as means and standard deviations of the means. Protein, fat, and carbohydrate provided about 40, 12, and 48%, respectively, of total energy intake; vitamin C was > 200 mg/day. Only dietary fat was significantly (p < 0.05) associated with TC for females. Fiber was significantly associated with HDL-C and HDL2-C for males and with HDL-C for females. Vitamin C was significantly associated with HDL C,HDL2-C, and HDL3-C for males, and with HDL-C and HDL3-C for females. These findings are consistent with those reported by Bazzarre et al. in farmers and suggest that vitamin C may favorably influence HDL-C metabolism. PMID- 1299499 TI - Ornithine supplementation and insulin release in bodybuilders. AB - Ornithine supplementation has gained popularity with athletes because of its alleged potential to release anabolic hormones, factors governing skeletal muscle hypertrophy. Three female and nine male bodybuilders served as subjects in a study to test the effectiveness of oral ornithine in bringing about the release of insulin, an anabolic hormone. After an overnight fast, subjects were administered 40, 100, or 170 mg.kg-1 L-ornithine.HCl by mouth in a random fashion on three consecutive Saturday mornings. Blood samples were drawn at baseline (T = 0), 45, and 90 min afterward. Serum ornithine levels were elevated (p < 0.01) at T = 45 and 90 min for all three dosage levels. However, serum insulin did not change from baseline levels at any dose of ornithine. The present findings show that ornithine is not an insulin secretagogue. PMID- 1299500 TI - The effect of protein supplementation on lactate accumulation during submaximal and maximal exercise. AB - Eleven subjects performed a graded exercise test after 1 week of protein supplementation (PRO) or glucose polymer placebo (CON), randomly assigned in a double blind fashion. The exercise consisted of 3-min graded exercise bouts separated by 10 min of active recovery at zero pedal resistance. Subjects then performed a 30-sec Wingate test (WIN) to assess performance during supramaximal exercise. Blood samples were obtained in the last 15 sec of each exercise and recovery period. PRO resulted in a decrease in blood lactate following 120% VO2max and WIN, an increase in blood alanine at all time points, and lower postexercise muscle lactate and glycogen. Resting muscle GPT activity was 47% higher during the PRO trial. Mean power output during the WIN did not differ between PRO and CON. The WIN fatigue index was not significantly different between PRO and CON. The increased alanine may reflect increased transamination of pyruvate, thereby reducing the accumulation of lactate, which in turn had a marginal effect on performance during supramaximal exercise. PMID- 1299501 TI - Influence of carbohydrate ingestion on blood glucose and performance in runners. AB - Ten trained male runners performed a treadmill exercise test at 80% VO2max under two experimental conditions, carbohydrate (CHO, 7% carbohydrate) and placebo (P), to determine the effect of carbohydrate ingestion on endurance performance (treadmill run time), blood glucose concentration, respiratory exchange ratio (RER), and subjective ratings of perceived exertion (RPE). Treatment order was randomized and counterbalanced and test solutions were administered double-blind. Ingestion took place 5 min preexercise (250 ml) and at 15-min intervals during exercise (125 ml). Performance was enhanced by 29.4% (p < 0.05) during CHO (115 +/- 25 min) compared to P (92 +/- 27 min). Blood glucose concentration was significantly greater during CHO (5.6 +/- 0.9 mM) relative to P (5.0 +/- 0.7 mM). There was a significant increase in mean RER following CHO ingestion (.94 +/- .01) compared to P (.90 +/- .01). Average RPE was significantly less during CHO (14.5 +/- 2.3) relative to P (15.4 +/- 2.4). These data suggest that time to exhaustion of high-intensity treadmill exercise is delayed as a result of carbohydrate ingestion and that this effect is mediated by favorable alterations in blood glucose concentration and substrate utilization. PMID- 1299502 TI - Effects of carbohydrate loading and weight-lifting on muscle girth. AB - Bodybuilders have used different carbohydrate loading regimens in conjunction with resistance exercise prior to competition in the belief that this would result in increased muscle size. To investigate this possibility, muscle girth measurements were obtained from nine weight-trained males before and after a control (standard isocaloric diet) and an experimental trial (carbohydrate loading). The latter regimen consisted of 3 days of intense weight-lifting while the subjects ingested a diet of 10% carbohydrate (CHO), 57% fat (F), and 33% protein (P), followed by 3 days of light weight-lifting and a day of rest while ingesting a diet of 80% CHO, 5% F, and 15% P. The control trial consisted of an identical weight-lifting regimen while subjects ingested an isocaloric (45 kcal/kg BW/day) diet. Body weight and girths (forearm, upper arm, chest, thigh, waist, and calf) were obtained before and after each trial in a relaxed and flexed state. The results indicate that an exercise/carbohydrate loading regimen had no significant effect on muscle girth as compared to the control trial. It is concluded that CHO loading has no additional advantage to enhancing muscle girth in bodybuilders over weight-lifting alone. PMID- 1299503 TI - Plasma ferritin concentration and physical work capacity in athletes. AB - This investigation aimed to determine whether the physical work capacity of nonanemic athletes could be improved when plasma ferritin concentrations of below 30 ng/ml were raised at least 15 ng/ml. The experimental group consisted of 15 training athletes, each of whose plasma ferritin concentration was less than 30 ng/ml (mean and SD of 19.8 +/- 8.4 ng/ml). In a control group of 16, each was measured with a plasma ferritin concentration of more than 40 ng/ml (mean and SD of 83.3 +/- 37.6 ng/ml). All participated in submaximal and maximal tests for aerobic and anaerobic power. Following iron supplementation, plasma ferritin concentration in each experimental subject increased by at least 15 ng/ml to more than 30 ng/ml, to a new mean of 46.3 +/- 15.5 ng/ml. The performance measures were also repeated, but no significant overall effects were associated with the increased plasma ferritin concentrations. These data provide no sound evidence that physical work capacity of athletes is enhanced when plasma ferritin concentrations of around 20 ng/ml are increased by at least 15 ng/ml. PMID- 1299504 TI - Effects of chromium picolinate on beginning weight training students. AB - Changes in body weight (BW), a sum of three body circumferences (sigma C), a sum of three skinfolds (sigma SF), and the one-repetition maximum (1RM) for the squat (SQ) and bench press (BP) were examined in 59 college-age students (37 males [M], 22 females [F]) over a 12-week weight lifting program. Using a double-blind protocol, half of the students were given 200 micrograms/day chromium (Cr) in the form of chromium picolinate (CrPic) while the other half received a placebo (P). Therefore four groups were randomly formed: F-CrPic (n = 12), F-P (n = 10), M CrPic (n = 18), and M-P (n = 19). All groups had significant increases in sigma C and significant decreases in sigma SF. No treatment effects were seen for the strength measurements, although the males experienced greater absolute increases. The only significant treatment effect found was due to the F-CrPic group gaining more BW (p = 0.0048) than the other three groups. It was concluded that CrPic supplementation had a greater effect on the females than on the males. PMID- 1299505 TI - Dietary intake and thiamin, iron, and zinc status in elite Nordic skiers during different training periods. AB - This study evaluated how different training periods affect dietary intake and biochemical indices of thiamin, iron, and zinc status in elite Nordic skiers. Subjects were 17 skiers and 39 controls, ages 18-38 yrs. Dietary data were collected by 7-day food records at 3-month intervals. Coefficient of variation (CV) was used to indicate magnitude of seasonal changes. Energy intake for the year (28 food record days) was 3,802 kcal/day (CV 19.1%) in male skiers, 2,754 kcal/day (CV 3.7%) in male controls, 2,812 kcal/day (CV 9.1%) in female skiers, and 2,013 kcal/day (CV 5.9%) in female controls. CVs for thiamin, riboflavin, vitamin C, calcium, magnesium, iron, and zinc intake were 14.1-23.9% (male skiers), 2.9-15.0% (male controls), 4.8-24.5% (female skiers), and 4.3-11.5% (female controls). Seasonal changes in energy, carbohydrate, and micronutrient intakes reflected energy expenditure in male endurance athletes particularly. Erythrocyte transketolase activation coefficients and serum ferritin and zinc concentrations did not differ between skiers and controls. Seasonal variations in these biochemical indices of nutritional status were of the same magnitude in skiers and controls, despite large changes in skiers' physical activity. PMID- 1299506 TI - Hematological status of male runners in relation to the extent of physical training. AB - Blood biochemical indices of iron status were measured in venous blood from 20 runners and 6 control subjects. All subjects were male, ages 20 to 40 years, and stable with regard to body weight and degree of physical activity. Dietary analysis was undertaken using a 7-day weighed food intake. There was no evidence of iron deficiency: hemoglobin concentrations and serum ferritin levels were within the normal population range for all individuals. However, serum ferritin was negatively correlated with the amount of training. Daily iron intake appeared to be adequate; iron intake was correlated with protein intake but not related to training or energy intake. Serum ferritin, an indicator of iron status, was significantly correlated with vitamin C intake but not iron intake. Serum transferrin concentration was higher in the group of athletes undertaking a high weekly training load compared with the control subjects, suggesting an alteration in iron metabolism although there was no evidence of increased erythropoiesis. The biological significance of this is unclear. PMID- 1299507 TI - Effects of low ferritin concentration on endurance performance. AB - To determine the effects of depleted iron stores on endurance performance and blood lactate concentration, eight active women with normal (> 26 ng/ml) and eight with low (< 12 ng/ml) plasma ferritin concentrations were studied while performing a VO2max and an endurance test (80% VO2max) on a cycle ergometer. The low ferritin group had significantly lower serum iron concentration and transferrin saturation and higher TIBC than the normal ferritin group. Mean VO2max was not significantly different between groups. No significant difference was found in total time to exhaustion during the endurance test for low (23.2 min) and normal (27.0 min) ferritin groups; however, the normal ferritin group exercised 14% longer. Blood lactate concentrations following the VO2max and endurance test did not differ significantly between groups. Food diaries revealed lower daily absorbable iron intake by the low ferritin group compared to the normal ferritin group. Ferritin concentration was significantly related to absorbable iron (r = .72) and total iron (r = .70) intake. The results suggest that women with depleted iron stores who are not anemic may have less endurance, but do not have higher blood lactate during exercise than women with normal iron stores. PMID- 1299508 TI - Effects of caffeine ingestion on metabolic responses to prolonged walking in sedentary males. AB - This study examined the effects of a single dose of caffeine (5 mg.kg-1) on energy metabolism during 60-min treadmill walking at light (30% VO2max) and moderate (50% VO2max) aerobic intensities in eight sedentary (VO2max) 39.6 +/- 3.1 ml.kg-1 x min-1) males. Caffeine intake 60 min prior to walking exercise increased pre- and postexercise FFA, glycerol, and lactate concentrations (p < 0.05). Blood glucose levels following walking trials were lower than preexercise values (p < 0.05). Gas exchange indicated that caffeine did not change exercise oxygen uptake, RER values, and carbon dioxide production (p > 0.05). In contrast, a small but statistically significant effect of caffeine on exercise minute ventilation was noted (p < 0.01). It is concluded that ingestion of 5 mg.kg-1 caffeine increases the mobilization of energy substrate from fat sources; however, the present data do not provide evidence of a caffeine-induced shift in energy substrate usage. Caffeine is not an effective means for enhancing the energy cost of prolonged walking. PMID- 1299509 TI - [Isolated and unilateral malacoplakia of the upper urinary tract. Apropos of a case]. AB - Malakoplakia, strictly unilateral and localised to the upper urinary tract, is a rare presentation of this uncommon inflammatory disease. In this 53 year old woman, the disease presented in the form of a tumour of the left upper urinary tract. Radical nephroureterectomy was performed and histological examination of the resection specimen revealed the diagnosis. PMID- 1299510 TI - [Protection of male fertility during anticancer treatment: animal experiments]. AB - One of the best known iatrogenic effects of anticancer treatments is the sterility of young patients with a good prognosis, hence the necessity to develop a protocol enabling us to preserve male reproductive function. This review of the literature summarises the various approaches investigated in order to obtain protection of spermatogenesis prior to radiotherapy and/or chemotherapy. Most of these pathways involve hormone therapy based on regulation of the hypothalamo hypophyso-testicular axis. Animal models are generally used in these experiments. The various applications in man are described and discussed. PMID- 1299511 TI - [The physiology of penile rigidity]. AB - Penile tumescence and rigidity are considered to be a purely vascular process related to an increased inflow and a decreased outflow. This theory, which provides a satisfactory explanation for tumescence, is unable to explain the existence of high intracavernous pressures recorded both in animals and in man. Based on a hydrostatic model, the authors distinguish two phases involving different physiological mechanisms: an infrasystolic vascular phase and a suprasystolic muscular phase. During the vascular phase, the intracavernous pressure (ICP) can never exceed the systolic blood pressure. However, during the muscular phase, the ICP largely exceeds the systolic pressure, reaching values as high as 400 mmHg in man and 1,000 mmHg in animals. These variations in ICP can be explained by the contraction of perineal muscles, particularly the ischiocavernosus muscles. Various animal and human experiments are presented in support of this hypothesis. The pressure variations exerted on the glans during coitus by the perivaginal musculature are sufficient to induce reflex contractions of the ischiocavernosus muscles, promoting penile rigidity. PMID- 1299512 TI - [An analysis of the organization, profile of the clientele and pathologies managed in the urology division of the Public Assistance-Hospital of Paris. A 15 day cross-sectional survey of 10 services]. AB - A cross-sectional study was carried out in ten urology departments over a two week period. Three categories of data were collected concerning socio-economic status and epidemiological profiles and management of the patients. The results are presented with comparative analysis of performance of the clinics, and the epidemiological data are analysed with reference to the inpatient case mix. PMID- 1299513 TI - [Spyridion Oeconomou (1886-1975), eminent urologist and benefactor of hippocratism]. PMID- 1299514 TI - [Scrotal hyperthermia and male infertility]. PMID- 1299515 TI - [Electrostimulation of anterior sacral nerve roots in spinal cord injury patients (evaluation of the 1st 25 cases)]. AB - The authors analyse the first 25 patients with spinal cord injuries treated by G. Brindley's technique based on section of the posterior sacral nerve roots to control detrusor hyperexcitability and electrostimulation of the anterior sacral nerve roots to ensure bladder emptying and to facilitate erection and defecation. The indications for this technique are essentially unstable bladders with incontinence and certain hypoactive bladders. The following results were obtained: Acquisition of continence in 90% of cases. Bladder capacity was always greatly increased. Almost complete bladder emptying in the majority of cases. Very marked reduction in urinary tract infection. Regularization of intestinal transit. The complications of this surgery were uncommon but serious: C.S.F. leaks, Postoperative denervations. Sepsis. Material or cable failure. PMID- 1299516 TI - [Endoscopic treatment of vesico-ureteral reflux after reimplantation of the ureter (transplants excluded)]. AB - O'Donnell's technique was used to treat 9 refluxing ureteric units after surgical reimplantation of the ureter in 8 patients (mean age: 45 years) between May 1986 and January 1991. The reimplantation was performed according to Cohen's technique in 5 cases (including ureteric remodelling in one case), Leadbetter's technique in 2 cases (including ureteric remodelling in one case), the Campos Freire technique in 1 case and a direct reimplantation in 1 case (with Boari). The reflux was grade II for 1 ureter, grade III for 54 ureters, grade IV for 2 ureters and grade V for 1 ureter. A single injection was performed in 5 patients and multiple injections were required in 3 patients. An associated bladder neck incision was performed in 2 male patients. No complications were observed. Correction of reflux was obtained for 8 ureteric units, i.e. 87% success with a mean follow-up of 28 months. The failure corresponded to the case of grade V reflux in a megaureter reimplanted with remodelling. The authors recommend that endoscopic treatment of reflux be performed as first-line treatment for reflux of reimplanted ureters because of the simplicity and efficacy of this technique. PMID- 1299517 TI - [Gangrenous conditions of the perineum and the genital area. Apropos of 15 cases]. AB - The authors report 15 cases of gangrene of the perineum and genital organs: 10 patients with urological lesions (urethral stricture: 6 cases, benign prostatic hypertrophy: 3 cases, bladder stones: 1 case) and 5 patients with Fournier's disease. The unexpected recrudescence of this disease, its persistent severity, the limits of our understanding of the pathogenesis and the therapeutic problems involved, led the authors to analyse this series of cases which, despite an apparent diversity of aetiologies, retained common anatomical, bacteriological and therapeutic features. They stress the importance of emergency surgery, appropriate antibiotics and postoperative intensive care. The mortality remains high (5 patients in this series died). PMID- 1299518 TI - [Urinary calculi in the Surgical Departments of the National Hospital Center and the University of Cotonou]. AB - The authors review renal stone disease in the National University Hospital of Cotonou on the basis of 109 cases observed over a period of 18 years. The mean frequency was 6.11 cases per year with a marked male predominance (sex ratio of 3.73). Infection and diseases of the lower urinary tract play an important aetiological role, hence the numerical importance of cases of lower tract stones (60.95%). PMID- 1299519 TI - [Iliac artery-ureteral fistula after aorto-iliac reconstructive surgery (apropos of 3 cases)]. AB - The authors report 3 cases of ilio-ureteric fistulae following aorto-iliac reconstructive surgery. They also review 6 similar cases published in the worldwide literature. All of these cases have in common the appearance of a uretero-arterial fistula several years after the vascular operation on the iliac artery. The postoperative course of iliac thromboendarterectomy appears to be principally responsible, as in the 3 cases presented here, resulting in a pseudoaneurysm over the arteriotomy closure, especially as a patch angioplasty had been performed. This complication is exceptional. The diagnosis must be suspected in the case of profuse haematuria and a suggestive history and should be confirmed, when possible, by intravenous urography, retrograde ureteropyelography, arteriography, or even computed tomography. Treatment is complex and consists of a vascular and urological procedure depending on the degree of urgency and the possibilities of reconstruction. PMID- 1299520 TI - [Non-specific bacterial ureteritis: a rare entity]. AB - Based on a recent case of non-specific bacterial ureteritis, the authors review the clinical features of what has now become a rare disease. They also evaluate the role of computed tomography in the differential diagnosis of this disease. PMID- 1299521 TI - [The valves of the ureter. Apropos of 2 cases]. AB - The authors report two cases of congenital ureteral valves of the upper third of the ureter complicated by renal stone in two children and diagnosed by I.V.P. The two patients underwent a resection of the pathological segment and a pelvic ureteral anastomosis successfully. The review of the literature data regarding ureteral valves allowed to emphasize the uncommon of the bilateral form complicated by renal stone and the better preoperative diagnosis by ureteroscopy and antegrade pyelogram. PMID- 1299523 TI - [The diagnosis of uterine leiomyosarcoma and endometrial stromal sarcoma]. AB - The diagnostic problems in uterine smooth muscle tumors and endometrial stromal tumors are reviewed and discussed with analysis of 14 selective cases collected from the affiliated hospital. Data suggested that, in the differential diagnosis of benign and malignant uterine smooth muscle tumors, it is not comprehensive to use mitotic activity as the only criterion. Nuclear atypia and some other clinico pathological features should be considered together, and, it is important to recognize the "mitotic active" leiomyoma which runs a benign course despite a high mitotic rate. In endometrial stromal sarcoma, the growth pattern and the extent of tumor spreading seem not closely correlated with the mitotic activity, nor the atypia, and, the clinical stage was considered as a significant reference in the prognosis. Thus, it is suggested that the differentiation of endometrial stromal sarcoma into low and high malignancy according to the mitotic rate alone is not the best reliable guide in evaluating the tumor behavior. It is emphasized that the extent of spreading of the tumor should be stated in the diagnosis. Immunohistochemical study revealed that the sex cord element in endometrial stromal sarcoma and other uterine tumors expressed a myogenous rather than an epithelial phenotype. PMID- 1299522 TI - [Pathological observation on the new classification and features of ovarian tumors]. AB - Cases were presented to describe the clinical manifestations, histological features, and diagnostic criteria about the current classification of ovarian tumors. They included peritoneal serous borderline tumor, endocervical-like the intestinal-type mucinous borderline tumor, transitional cell carcinoma of ovarian surface epithelial-stromal tumors and juvenile granulosa cell tumor, sclerosing stromal tumor, hepatoid yolk sac tumor, and primary mucinous carcinoid tumor of non-surface epithelial ovarian tumors. Cases were also presented for discussing the significance of structures and features of some ovarian tumors which have been reevaluated and newly classified. For instance, tumor cell of granulosa cell tumor gives vimentin expression, but is unable to express cytokeratin in all the cases detected with monoclonal antibody of CK-2. Based on the clinical manifestations, exact locating site in the ovary, as well as the histology and histochemistry features, it is possible to identify the stromal luteoma, leydig cell tumor, and non-specific steroid cell tumor respectively in the family of steroid cell tumors. Additionally, the diagnostic significance of the occurrence of basal membrane-like substance and intestinal cells in some yolk sac tumors is also discussed. PMID- 1299524 TI - [Histopathologic study on lymphadenopathy in HIV infected patients]. AB - Histopathologic study on the lymphadenopathy of 38 HIV infected patients in Zambia are reported. The histologic type of lymph node changes might be divided as follows: follicular hyperplasia, mixed follicular hyperplasia, follicular involution, and lymphocyte depletion. The author points out that although each individual histologic change in lymph node is not specific, the summation of changes in lymph node are characteristic. A diagnosis of HIV infection might be considered, and appropriate test is warranted, when histologic changes are found in enlarged lymph nodes at two or more noningunal sites for several months. Lymph node biopsy is recommended and significant in discovering HIV infected cases, making diagnosis of AIDS as well as AIDS-related complex, and evaluation of prognosis of these patients. PMID- 1299525 TI - [Study on mast cells in experimental silicosis]. AB - Quantitative and ultrastructural changes of mast cells (MC) were studied in rat lungs after inhalation of quartz particles. The number of degranulating MC was remarkably increased two weeks and 4 weeks after quartz inhalation (P < 0.05). The average number of the MC per unit area (mm2 of tissue section) and distribution in both experimental and control groups were similar and the mast cells were mainly distributed in the subpleural, perivascular and peribronchial connective tissues. The average number of MC per unit area significantly increased with pulmonary fibrosis three months later. Most of them infiltrated in the fibrotic alveolar septa and fibrotic areas, and the number of degranulating MC was also remarkably increased (P < 0.05). In addition, electronic microscopy showed that mast cells came into contact with fibroblast-like cells and the mast cells usually became degranulated in appearance. These results suggest that there is a close relationship between MC and silicotic fibrosis. PMID- 1299526 TI - [A comparative study of c-sis and c-myc and cellular phenotypes in the arterial media and atherosclerotic plaques]. AB - C-sis and c-myc oncogene probes, random primed DNA labeling with digoxigenin-dUTP and technique of dot blot hybridization by enzyme immunoassay were used to study both c-sis and c-myc gene expression in the arterial media and atherosclerotic plaques collected from human aortae. In addition, the ultrastructure of smooth muscle cells (SMCs) in these specimens was also examined. The results showed that c-sis and c-myc gene expression was increased in the atherosclerotic plaques. The contractile state SMCs and synthetic state SMCs were obtained in the arterial media and the atherosclerotic plaques respectively. The results indicated that different phenotypes of SMCs might give different c-sis and c-myc gene expressions. PMID- 1299527 TI - [Establishment of the vascular intimal model in vitro and its application in studying atherosclerosis]. AB - An endothelial culture model in vitro mimicking the vascular intima in vivo was designed which was composed of an upper and a lower well separated by a layer of amnion membrane, and upon which endothelial cells (ECs) isolated from the human umbilical vein were cultured. The upper well, the subendothelial amnion, and the lower well were analogical to the vascular lumen, the subendothelial tissue and the extravascular space, respectively. In comparison with the ECs cultured on the plastic, dishes, ECs cultured on the amnion membrane maintained more morphologic features as in vivo and could be cultured for up to 15 days without apparent detachment. Monocytes, loaded in the upper wells, were able to adhere to the cytoplasmic membrane of ECs. Furthermore, with the presence of the chemotactic factor (fMLP) in the lower well, monocytes showed active migrating ability passing through the EC junctions. If LDL (100 micrograms/ml) was added in the media simultaneously, monocytes might be aggregated beneath the subendothelial space and some of them took an foamy appearance. In conclusion, the culture model is of value in the study of experimental inflammation and atherosclerosis. PMID- 1299528 TI - [Study of the pisum sativum agglutinin receptors and DNA ploidy during carcinogenesis in esophageal epithelium by flow cytometry]. AB - The relative mean contents of pisum sativum agglutinin receptors and DNA of human normal esophageal epithelium, its atypical hyperplasia as well as esophageal carcinoma were determined respectively by flow cytometry. The results revealed that the relative mean contents of pisum sativum agglutinin receptors which denote membrane composition and DNA which denote nuclear composition were increased gradually from normal, dysplastic and then malignant esophageal tissues. This suggested that during the neoplastic transformation, changes of the cell membrane component may correlate with changes of the cell nuclear component. PMID- 1299530 TI - [Pulmonary blastoma: a light-microscopic, immunohistochemical and electron microscopic study of six cases in childhood]. AB - Pulmonary blastoma is a very rare primary tumor of the lung, which mostly occur at a late age in adults. Six cases in children under four years of age are reported in this series. The light-microscopic, immunohistochemical and electron microscopic characteristics revealed that the elements of P.B. in childhood consist mainly of mesenchymal components, including undifferentiated large cells and small round cells, which tend to differentiate toward rhabdomyosarcoma. The epithelial components comprise only a small portion of the total tumor, and most appear as the well-demarcate branching tubular structures lined with columnar or cubiodal epithelium merging with the stroma. The degree of differentiation of mesenchymal elements is closely related to the prognosis. PMID- 1299529 TI - [Mitochondrial myopathy of progressive external ophthalmoplegia]. AB - Ten cases of blepharoptosis and chronic progressive oculomuscular paralysis are reported among which three had limb muscular weakness. Sex: male 5, female 5. Age: 16-58 years old. Age of onset: 7-38 years old. DURATION: 2-26 years. Muscle biopsy showed ragged red fibers, abnormal mitochondria and paracrystalline mitochondrial inclusions under both light and electron microscopy. All cases were diagnosed as CPED (chronic progressive external ophthalmoplegia) clinically and abnormal mitochondria pathologically. PMID- 1299531 TI - [Detection of G-->T mutation at codon 12 of H-ras oncogenes in gastric cancers with polymerase chain reaction and oligodeoxynucleotide(PCR-ODN)]. AB - DNA was extracted from paraffin-embedded gastric cancer tissues, and the possibility of G-->T mutations present at codon 12 of H-ras oncogenes was detected in Chinese gastric cancer patients with polymerase chain reaction (PCR) and oligodeoxynucleotide (ODN) probe hybridization. Point mutations were identified in 5 of 17 gastric cancer cases (29.4%), and in none of 7 gastric ulcer cases. These results indicate that G-->T mutations at codon 12 of H-ras oncogene may play a role in activating the oncogenes in gastric cancers. PMID- 1299532 TI - [Clinicopathological analysis of 20 cases of giant cell granuloma of the jaw]. AB - The pathological features of 20 cases of giant cell granuloma and 12 cases of giant cell tumor of the jaw were compared. Specimens of 8 cases of giant cell granuloma and 5 cases of giant cell tumor were stained with Wilder's reticular fiber stain and trichromic stain. The results showed that reticular fibers and collagenous fibers were more abundant and more focal in distribution in giant cell granulomas than in those of giant cell tumors. It is concluded that the two staining methods adopted are helpful in the differential diagnosis between these two kinds of diseases. PMID- 1299533 TI - [Extra-long trapezius myocutaneous fascia flap for repairing burn scar contracture of the neck]. AB - This flap is based on the transverse cervical artery and its descending branch and only includes a small portion of trapezius muscle tissue around the vascular pedicle. Both the length and width of the flap can exceed that of the traditional trapezius flap. So this flap is particularly suitable for repairing late-burn scar contracture of the neck. In addition, this flap has the potential to be used as a large free flap. PMID- 1299534 TI - [Studies on the aggregation of rat Sertoli cells, germ cells and peritubular cells in vitro]. AB - Dissociated testicular cell suspensions from 5, 10, 15, 20 and 25 day postnatal rats were cultured either on solid agar as a substratum or in a flask under slow rotation. Spherical or cord-like aggregations were formed from cells under both conditions. Sections from the aggregations showed that they were comprised mainly of Sertoli cells, with peritubular cells located around the aggregations. A few germ cells were present within those aggregations from cultures of rat testicular cells younger than ten days, while no germ cell could be found within aggregations from rats older than fifteen days. Based on these observations, we conclude that testicular cells in post-natal rats still maintain a limited capacity for cell adhesion and recognition and are thus able to form cellular aggregations. PMID- 1299535 TI - [Further studies of collagen biosynthesis by hepatocytes]. AB - Electron microscopic observation was carried out on 32 biopsies from liver and biliary system diseases. It was found that proliferative collagen in the liver was located not only in the portal space and Disse space, but also in the hepatocytes. Most of the collagen seen in hepatocytes were in the form of collagen fibrils, oriented irregularly, intermingled with the organelles and without a delimiting membrane. Therefore, the authors suggest that these collagen fibrils were produced by the hepatocytes themselves. PMID- 1299536 TI - [Study on the peritoneal stomata and absorptive mechanism of ascites]. AB - The peritoneal stomata in sixteen human specimens were studied by SEM, TEM and ODO freeze fracture techniques. In order to prove that the peritoneal stomata are the passage ways by which ascites is absorbed from the peritoneal cavity, animal experiments were performed. The results showed that the peritoneal stomata, which were only found between the cuboidal cells, were formed by the cytoplasmic processes of nearby cells. There were no basement membranes in the peritoneal stomata or the cuboidal cells which formed the peritoneal stomata. Microfilaments were observed in the cuboidal cells. Cytoplasmic processes of mesothelial cells and networks of connective tissue were found in the peritoneal channels. These had networks which formed the floor of each stomata and the roof of each lacunae. We observed that numbers and diameters of the peritoneal stomata were increased in mice with ascites. Red cells and carbonic particles injected into the peritoneal cavity were absorbed by the peritoneal stomata. So the microfilaments of the cuboidal cells, the cytoplasmic processes, and the fiber networks in the peritoneal channels can adjust the absorptive properties of the peritoneal stomata. The peritoneal stomata are an important pathway for draining ascites from the peritoneal cavity. PMID- 1299537 TI - [Molecular cytogenetic study of short arm aberrations in human D and G group chromosomes]. AB - Many structural and functional characteristics in the cen-pter regions of human D and G group chromosomes play important roles in the etiology of genetic diseases and cancer. Six cases of Dp+/Gp+, 10 cases of D/G translocation, 1 case of extra small chromosome (mar), and 1 case of Yqs were studied with molecular and cytogenetic techniques. The results showed the Ag-NOR frequency of the Dp+/Gp+ group to be significantly higher, but their satellite association frequency lower than those of normal controls. Autoradiographic silver grains were not found along the entire p+ part of the marker chromosome by using chromosomal in situ hybridization techniques. This result is somewhat different from what we had reported previously. It is suggested that the mechanism of p+ formation may vary among different cases. Diversified nucleolar organizer transcription sites may exist in the rRNA gene cluster region of chromosomes. The results of Ag-NOR and in situ hybridization of D/G translocation cases indicate that they have lost their NOR. Study of the extra small chromosome case and the Yqs case suggested that mar and Yqs exert no effect on the phenotype. PMID- 1299538 TI - [Effect of bradykinin, ionophore A23187 and trypsin on prostacyclin release from calf and pig aorta endothelial cells]. AB - This paper details the methods of establishing stock culture and subculture of calf and pig aorta endothelial cells and the effects of bradykinin, ionophore A23187, trypsin and arachidonic acid (AA) on the release of prostacyclin (PGI2) from the cells. The release was measured by 6-keto PGF1 alpha radioimmunoassay. The results showed that the stimuli significantly increased the release of PGI2 in the two endothelial cell types (P < 0.01, n = 8), and the release was much stronger in pig than in calf endothelial cells under the experimental conditions. We therefore suggest that the reactivities of the two endothelial cells to the stimuli differ. The results offer useful information for further research of the mechanism of their pharmacologic actions on endothelial cells and their relationship with PGI2. PMID- 1299539 TI - [Effects of GTW and T4 from Tripterygium wilfordii Hook f. on LH cells in male rat pituitary glands]. AB - Using anti-beta-LH monoclonal antibodies, studies were undertaken to assess the effects of the glycosides (GTW) and T4 from Tripterygium wilfordii Hook f. on LH cells in male rat pituitary glands using immunohistochemical methods and ultrastructural observation. The results showed that there were more vacuoles in the cytoplasm of LH cells and the color density of immunohistochemical staining was much stronger in the treated groups than that in the control group. Electron microscopic results showed that the nulei of LH cells were shrunken and the Golgi complexes and the rough endoplasmic reticula were largely expanded in the treated groups. The mechanism of these changes is similar to that in "castration cells." PMID- 1299540 TI - [Inhibitory effects of several antitumor drugs on the growth of HL-60 cells in SRC of mice]. AB - Human promyelocytic leukemia HL-60 cells provide a useful model system for the study of cell differentiation in vitro. Here the growth of HL-60 cells as a solid clot with fibrin in subrenal capsules (SRC) of mice was studied. The cell volume of HL-60 cells increased 5 and 15-fold between 6-9 days after transplantation into normal and CYT immunosuppressed mice, respectively. Histological study revealed typical proliferation and invasion characteristics of HL-60 cells and higher tumor cell density. RA, RII, Ara-C, Harringtonine and HMBA significantly inhibited the growth of HL-60 cells in SRC of mice. This model provides a useful system for the study of the effect of drugs on cultured tumor cells or leukemia cell lines in vivo. PMID- 1299541 TI - [Anti-carcinogenic and anti-promoting effects of retinoid R8605]. AB - R8605 belongs to the third generation retinoid and was found during the systematic screening of cancer chemopreventive agents in our institute. Based on the theory of multistage carcinogenesis, the anti-carcinogenic and anti-promoting effects of R8605 as well as its possible anti-promoting mechanisms were studied. Experiments proved that R8605 (50 mg/kg and 25 mg/kg, i.g.) significantly inhibited the growth of skin papillomas induced by 7, 12 dimethylbenz[a]anthracene and croton oil in mice and exhibited a potent anti promoting action. In addition, R8605 (50 mg/kg and 25 mg/kg, i.g.) strongly inhibited the induction of ornithine decarboxylase (ODC) activity of mouse skin epidermis by croton oil. At a dose of 100 mg/kg of R8605 (i.g.) croton oil induced ear edema in mice was suppressed. These results suggest that the anti promoting effect of R8605 might be associated with its anti-inflammatory action and its inhibitory effect on ODC activity. PMID- 1299542 TI - [The pathologic myocardial change caused by intracoronary ethyl alcohol injection and its mechanism]. AB - Intracoronary chemical injection to ablate ventricular tachycardia is a new method. Through experiments in 22 dogs, we studied the pathologic change of the myocardium and its mechanism following intracoronary injection of 96% ethyl alcohol. All dogs receiving ethyl alcohol injection displayed myocardial necrosis, and most of them presented thrombus in the coronary branch. The pathologic change in the acute period may have resulted from direct ethyl alcohol damage, and that in the late period may have resulted from both direct damage and thrombus caused by arterial damage. PMID- 1299543 TI - [The changes in plasma renin angiotensin and arginine vasopressin in pulmonary hypertension rats]. AB - The plasma renin activity (RA), the concentration and the ratio of angiotensin (AI) conversion into angiotensin II (AII), and arginine vasopressin (AVP) level were observed in Wistar rats with pulmonary hypertension (PH) induced by extracardiac left-to-right shunting (LRS), hypobaric hypoxia (HH) and shunting plus HH (SHH). In comparison with normal control rats, RA in LRS and SHH rats showed an increasing trend, although no statistical significance appeared (P > 0.05). No change occurred in HH rats. The concentration and ratio of AI conversion into AII were significantly increased in LRS rats (P < 0.05), but decreased in HH and SHH rats (more markedly in HH rats). AVP increased significantly in LRS rats, and also showed an increasing trend in HH and SHH, but no significance was found (P > 0.05). The action of humoral factors in PH formation was discussed. PMID- 1299544 TI - [Generation of monoclonal antibodies (McAbs) against human luteinizing hormone (hLH) in a methylcellulose semi-solid medium]. AB - McAbs against hLH were generated by a facile hybridoma technique according to the methods of Davis and Lee, et al. After routine immunization and cell fusion, the cells were plated in a semi-solid medium containing methylcellulose and HAT. Five to seven days later, visible clones were removed for subculture in DMEM liquid medium containing 15% FCS and then screened by ELISA. As a result, 12 hybrid cell lines secreting McAbs to the LH-B subunit were obtained. These Abs have been used in clinical diagnostic and immunohistochemical work, showing good results. The advantages of the semi-solid medium in preparing McAbs are discussed. PMID- 1299545 TI - [Splenectomy in four cases of hairy cell leukemia]. AB - This paper reports the experimental diagnosis of hairy cell leukemia and the results of splenectomy in 4 cases. Three patients were examined using histochemical methods and anti-leukocyte differentiation monoclonal antibodies. All of them were diagnosed as hairy cell leukemia of B lymphocytes. The effects of splenectomy were found to be related to chemotherapy used before and after operation. Hairy cell leukemia complicated with megalosplenia or hypersplenism were indications for splenectomy. PMID- 1299546 TI - [Purification of the ninth component of human complement (C9)]. AB - A large amount of human C9 was purified from plasma by the following procedures: 1) Polyethylene glycol precipitation; 2) Depletion of plasminogen by passing over an L-lys-sepharose column; 3) DEAE-sephadex A-50 chromatography; and 4) Hydroxylapatite (HA) chromatography. The method of C9 purification was improved by altering the column-elution conditions and by the establishment of a novel method for preparing high-flow-rate HA. As a result, the rate of recovery of C9 was high (28.2%) and no impurities were detected either on gel electrophoretic or immunochemical examination. The hemolytic activity of purified C9 was retained. PMID- 1299547 TI - [Subungual exostosis of the digits]. AB - From 1980 to 1990, twenty-two patients with subungual exostosis were treated in PUMC Hospital and the Sixth Hospital of Beijing. The incidence of subungual exostosis accounted for 4.6% of all bone tumor. Post-adolescents and young adults were commonly affected. The female:male ratio was 1.75 to 1. The great toe was the most commonly affected site. Radiological findings were diagnostic, and local tumor excision is the treatment of choice. PMID- 1299548 TI - Significance of western blot in diagnosis of cysticercosis cellulosae. AB - Sodium dodecyl sulphate (SDS) polyacrylamide gradient gel electrophoresis (PAGE) and immunoblot were used for the diagnosis of patients with cysticercosis cellulosae. 26 KD protein band of the whole Cysticercus antigen showed a high specificity to the sera from patients with cysticercosis cellulosae and had no cross reaction with sera from normal controls and other parasitic diseases including hydatidosis. The positive rate of Western blot with 26 KD band was 70% and the results showed no significant difference in comparison with those of CFT and ELISA. PMID- 1299549 TI - Beneficial effects of berberine on hemodynamics during acute ischemic left ventricular failure in dogs. AB - In 18 dogs ischemic left ventricular failure characterized by a 30 percent reduction in peak rate of rise of left ventricular pressure (+dp/dt) and elevation of left ventricular end-diastolic pressure (LVEDP) to 15 mmHg or more was produced by ligation of the proximal left anterior descending coronary artery followed by serial occlusions of the distal left circumflex coronary artery. In 10 days, administration of berberine in an intravenous bolus injection (1 mg/kg, within 3 minutes) followed by a constant infusion (0.2 mg/kg/min, 30 minutes) increased the cardiac output (CO) from 1.25 +/- 0.12 to 1.61 +/- 0.17 L/min (P < 0.05), and +dp/dt from 810 +/- 85 to 1021 +/- 130 mmHg/s (P < 0.01), and decreased LVEDP from 16.5 +/- 1.3 to 12.0 +/- 1.0 mmHg (P < 0.05), diastolic blood pressure from 94 +/- 6 to 84 +/- 5 mmHg (P < 0.01), systemic vascular resistance from 7303 +/- 278 to 5442 +/- 231 dynes.x/cm5 (P < 0.01), but did not affect the heart rate. Injection of 5% glucose with the same volume did not improve CO and dp/dt (P > 0.05) but increased the LVEDP from 17.1 +/- 1.4 to 17.8 +/- 1.6 mmHg (P < 0.01) in 8 dogs. The levels of plasma concentration of berberine was determined with high-performance liquid chromatography. The changes in plasma drug level were found parallel to hemodynamic effects of berberine. The results of this study showed that berberine was able to improve the impaired left ventricular function by its positive inotropic effect and mild systemic vasodilatation. PMID- 1299550 TI - Lectin histochemistry in psoriasis, lichen planus and seborrheic keratosis. AB - Lectin binding patterns in psoriasis, lichen planus and seborrheic keratosis lesions were studied using 14 different biotinyl lectins and avidin-horseradish peroxidase. Compared with normal epidermis, there were significant quantitative and qualitative differences, some of which were characteristic. PMID- 1299551 TI - Chemosensitivity of salivary gland and oral cancer cell lines. AB - Chemosensitivity of salivary gland and oral cancer cell lines to 14 antitumor drugs was tested using a tetrazolium-based colorimetric assay and the relative antitumor activity (RAA) of the drugs was compared. Adriamycin (ADM), methotrexate and fluorouracil (5-FU) showed the most potent RAA against the cell lines while cantharidin did not. The rank orders of other 10 drugs against each cell line differed from each other. PMID- 1299552 TI - Chronic complex volar dislocation of metacarpophalangeal joint. PMID- 1299553 TI - Statistical information on the development of China's health work in 1991. Report from the Information Centre of Health Statistics of the Ministry of Public Health of China. PMID- 1299554 TI - Cell protection mechanism of antishock action of anisodamine. AB - Anisodamine was used as an antishock (chiefly septic) drug beginning in the early 1960s in China. Its underlining mechanism was believed to be due to its vasodilative action. But in normal animals it only produces slight vasodilation. Our work during the recent 15 years proved that anisodamine is not only beneficial in the treatment for septic shock, but also for hemorrhagic, traumatic, and SMAO shock, and its mechanism of action are based on its following biological actions: (1) it has membrane stabilization and cell protection action, which was probably related to its calcium antagonist action; (2) it protects ischemia intestine from releasing shock factors; and (3) its inhibition of endotoxin binding to cells and tissue at the membrane level probably makes it an special antishock drug for septic shock. PMID- 1299555 TI - Titanium nails used in A-V fistulation for hemodialysis in 428 patients. AB - The 4-year experience in the clinical usage of titanium nails in making internal fistula for hemodialysis in 428 cases (17,829 dialyses) is reported. The results were satisfactory and no obvious complications were found. Being simple in practice and having a high success rate and less complications, this method has been applied at 86 hospitals in China. PMID- 1299556 TI - Transurethral resection in children with urethral stricture and occlusion. AB - Technical considerations of urethral surgery in children are critical because of the small size and delicacy of their urethra. From 1984 to 1989, 10 children with serious traumatic urethral stricture (5 cases) and occlusion (5) were treated satisfactorily by an improved transurethral resection (TUR). The age of the children ranged from 4 to 14 years. The TUR technique, curative effects and prevention of urethral stricture are discussed. PMID- 1299557 TI - Curative effects of highly active atrial natriuretic peptide on severe pregnancy induced hypertension. AB - A new highly active atrial natriuretic peptide (haANP), synthesized by a solid phase technique, was given by intravenous infusion to 20 patients with severe pregnancy-induced hypertension (PIH) and the curative result of haANP was observed. Compared with basal values, supine systolic and diastolic BP was lowered significantly (P < 0.01), which may be related to the specific receptor of hANP and inhibition of renin-angiotensin-aldosterone system (RAAS). The haANP was found to possess significant effects of antispasm, detumescence and reducing proteinuria, probably by repairing mildly injured glomerulae, strong effects of diuresis and improving heart function with no side effects. Auto-antibody of hANP was found in patients with severe PIH, which affected the function of target cells of highly concentrated endogenous hANP. This auto-antibody might be one of the causes for PIH. PMID- 1299558 TI - Isolation and sequencing of the cDNA encoding the 75-kD human sperm protein related to infertility. AB - Serum was obtained from an infertile woman (IS) inducing head-to-head agglutination of human sperm and was used to screen a human testis lambda gt11 cDNA library. A plaque producing the interacting antigen was located. The recombinant lambda gt11 was isolated and cut with EcoRI releasing a 0.7-kb cDNA. Using the 0.7-kb cDNA as a probe, a larger cDNA of 2.4 kb was isolated and its nucleotide sequence determined. It was composed of 2 427 nucleotides with an open reading frame of 1584 nucleotides encoding 528 amino acid residues. The specific antisperm antibody was isolated from IS by epitope selection, using positive plaques of E. coli Y1090. The epitope-selected antibodies interacted with a 75-kD human sperm protein and with a polypeptide in the form of a beta-galactosidase fusion protein in the recombinant lysate of E. coli Y1089, determined by immunoblot. The fusion protein was purified by affinity chromatography on an anti beta-galactosidase-Sepharose column. It is proposed that production of anti-75-kD antibodies may be the underlying cause of the infertility. PMID- 1299559 TI - [Visual function damage in primary open angle glaucoma (POAG) in relation to hemorheology, ocular rheograph and other factors]. AB - Researches of glaucomatous visual damage, hemorheology, ocular rheograph and other multiplex factors, with computed multifactorial stepwise regression analysis, indicate that elevation of intraocular pressure (IOP) is not the only factor to induce visual impairment. POAG patients are shown to have markedly reduced diastolic perfusion pressure in the ophthalmic artery, besides prolonged filling time of the retinal artery and vein, diminished erythrocyte deformability and increased platelet adhesion rate. The characteristic ocular rheographic changes in POAG patients of controlled IOP suggest that hemorheological factors play a role in the visual function damage. PMID- 1299560 TI - [Neuroretinal rim area (NRA) in early glaucoma]. AB - The authors photographically measured the optic disks in 6 groups, namely, normal subjects with small cups and those with large cups, suspected glaucoma with small cups and those with large cups, primary open angle glaucoma (POAG) and low tension glaucoma (LTG). The effect of ocular optical magnification was corrected. The mean NRAs of POAG, LTG and suspected glaucoma with large cups were found less than those of the other 3 groups. In the normal subjects, an evident positive correlation existed between the cup area and the disk area, and the NRA was weakly correlated with the disk area. The diffuse and localized retinal nerve fiber layer defects were negatively correlated with the NRA significantly. PMID- 1299561 TI - [Measurement of regional neuroretinal rim area in early open angle glaucoma]. AB - The mean total and regional neuroretinal rim areas (NRA) in early primary open angle glaucoma were found significantly reduced in comparison with those of normal controls, and in 10 glaucomatous eyes whose total NRAs were within the normal range, the suprotemporal regional NRA was less than the mean normal value, indicating that the measurement of regional NRA was more sensitive for the detection of early glaucoma. PMID- 1299562 TI - [Frequency distribution of earliest glaucomatous visual field defects]. AB - 42 eyes with established early glaucoma and normal visual field were followed-up with Goldmann perimetry for 2.5 years, during which time 24 eyes manifested reproducible glaucomatous visual field defects. The initial defects were characteristically shallow and located mostly in the superior Bjerrum region adjacent to the blind spot. This finding may be useful in designing protocols for the detection of early glaucomatous field defects. PMID- 1299563 TI - [Comparison of optic disc damages and fluorescein filling defect of the disc between low tension and primary open angle glaucoma]. AB - The neuroretinal rim area (NRA), the cup area and the ratio of absolute fluorescein filling defect of the disc were measured in 23 cases of low tension glaucoma (LTG) and 25 cases of primary open angle glaucoma (POAG) with fluorescein angiography and computerized image analysis. The results showed that the inferior and temporal quarters of NRA in eyes of LTG were significantly smaller than in eyes of POAG, while the ratio of absolute fluorescein filling defect of the disc in LTG was larger than in POAG, and the cup of LTG was larger than that of POAG, indicating that there might be different mechanisms of optic disc damages in the two types of glaucoma. PMID- 1299565 TI - [Intraocular pressure and optic nerve damages in monocular early glaucoma: a comparative study of primary open angle glaucoma and low tension glaucoma]. AB - The correlation of intraocular pressure (IOP) to optic nerve damages was studied in 17 patients of primary open angle glaucoma (POAG) and 24 patients of low tension glaucoma (LTG) both with monocular early glaucomatous damages. In the POAG group, the mean IOP was higher in the glaucomatous eye than in the other, while in the LTG group there was no significant IOP difference between the two eyes. Comparing the optic nerve damages in both groups, patients of POAG presented a concentrically enlarged cup with even disc rim and diffuse retinal nerve fiber layer defect (RNFLD), while patients of LTG exhibited a paracentrical cup with uneven disc rim and localized RNFLD. The results suggested that there could be different mechanisms of optic nerve damages in the two groups. PMID- 1299564 TI - [The anterior chamber depth after trabeculectomy]. AB - The anterior chamber depth was measured with the Haag-Streit Pachymeter in 26 cases (33 eyes) of primary angle-closure glaucoma preoperatively and postoperatively on days 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 30, 45 and 60. After successful trabeculectomy, the anterior chamber depth became shallower, particularly on days 2 to 4 postoperative, and then gradually deepened after day 5. By day 14 after surgery, the anterior chamber depth was recovered up to 91% of the preoperative level, and by day 30 up to 93%, to remain essentially stable thereafter. PMID- 1299566 TI - [Ultrastructural observations of the anterior chamber angle tissues in congenital glaucoma]. AB - 18 trabeculectomy specimens of congenital glaucoma were examined by light and transmission electron microscopy with the finding that the primary anomalies in congenital glaucoma included the developmental defect of trabecular meshwork, excessive collagen fibrils in the trabecular matrix, shifting forward of ciliary muscle fibers, and persistent mesenchymal tissue in the chamber angle. The authors also pointed out the importance of the secondary lesions of the trabecular meshwork in the pathogenesis of congenital glaucoma. PMID- 1299567 TI - [Extracapsular cataract extraction (ECCE) with posterior chamber IOL implantation in the very elderly]. AB - A study of the operations of ECCE with posterior chamber IOL implantation in 30 eyes of 25 patients aged 75-86 years showed that the average postoperative corrected visual acuity was 18/20, the average corrective spherical lens power was -0.70D and those of cylindrical power 1.18D(AR) and 1.33D(WR). There was no difference in operative complications between these very old and general elderly patients. However, since the health state was often compromised in the very old, to ensure uneventful operations, the ophthalmic surgeon should solicit advice from geriatricians, in addition to his own meticulous perioperative and postoperative care. PMID- 1299568 TI - [Correlation of diabetic retinopathy with systemic factors]. AB - Among 468 patients of diabetes mellitus, 208 cases having complete records of biochemical and ocular examinations were studied by stepwise multivariate regression, with regard to the correlation of diabetic retinopathy (DR) to systemic factors and ocular perfusion pressure. The results showed that the onset and severity of DR were positively correlated to proteinuria, duration of the disease, fasting blood sugar, and ocular perfusion pressure, negatively correlated to blood triglycerides, but not correlated to sex, the type of diabetes, and smoking or alcoholic habits. PMID- 1299569 TI - [Pattern visual evoked potential and pattern electroretinogram in patients with retinitis pigmentosa]. AB - The pattern visual evoked potential (PVEP) was analyzed in 22 patients (42 affected eyes) with retinitis pigmentosa, and in 9 cases the pattern electroretinogram (PERG) was simultaneously examined to find that (1) PVEP could be recorded in 31 (73.8%) and was normal in 17 (40.5%) of the affected eyes; (2) PVEP was related to visual acuity, being abnormal in all the eyes with visual acuity below 0.2, but normal in most eyes with visual acuity over 0.2; (3) the changes in PERG and PVEP were mostly consistent; and (4) PVEP and PERG might well be utilized for the morbid evaluation of central retina in patients with retinitis pigmentosa. PMID- 1299570 TI - [Keratitis associated with contact lens wear]. AB - Keratitis associated with contact lens wear in 50 eyes (37 patients) was analyzed. The results revealed that lenses of extended-wear induced more cases of keratitis than did lenses of daily-wear. The pathogenetic mechanism was discussed. PMID- 1299571 TI - [A clinical analysis of Graves' ophthalmopathy and ophthalmic Graves' disease]. AB - Clinical analysis of 29 cases of Graves' ophthalmopathy and 71 cases of ophthalmic Graves' disease showed that both identities had common ocular features of lid retraction, upper lid lag and exophthalmos, while Graves' ophthalmopathy tended to occur in later life, with longer morbid course, marked systemic symptoms and binocular involvement in contrast to ophthalmic Graves' disease. The clinical and differential diagnoses and treatment of the maladies were discussed. PMID- 1299572 TI - [Quantitative anatomical study of the fetal optic chiasmal capillaries]. AB - The spatial distribution of capillaries in the optic chiasma was studied quantitatively in 51 fetuses, 8 newborns and 4 babies to reveal that the capillary density was lower in the chiasmal median portion, which was therefore a weak point of blood supply. This finding may be a contributing factor for bitemporal hemianopsia due to neoplasms from the sella turcica. PMID- 1299573 TI - [An experimental study of ocular contusion and its hemodynamic changes]. AB - The hemodynamic changes in rabbit eyes following contusion were studied with rheoophthalmography (ROG), in which the wave amplitudes were markedly reduced and then recovered in 3 weeks, while in the anisodine-I treated group they recovered in 2 weeks. Contusion of 3 joules disrupted the choroidal circulation and damaged the retina. Anisodine-I improved the vasomotor functions of the choroidal vessels and was effective in treatment of ocular contusion. ROG was a sensitive objective means of estimating the severity of ocular contusion and evaluating the therapeutic effects. PMID- 1299574 TI - [Epidemiologic survey of senile macular degeneration]. AB - An epidemiologic survey of senile macular degeneration (SMD) was conducted among 3351 persons in Chenzhou District, Hunan. The research showed that the overall incidence of SMD was 5.88%, and that for persons over 65 years was 16.83%. Furthermore, the incidence was 7.33% among peasants, 4.94% among factory workers, 2.78% among office cadres, and 7.98% among miners. Under ophthalmoscopy and fluorescein angiography, 89.34% of the cases were of the atrophic type, and 10.66% the exudative type. Stepwise regression analysis was done with the computer; the conclusion was that the incidence increased with age and was related to occupation. The authors dwelt upon the relationship between light damage and the incidence of SMD. PMID- 1299575 TI - [A variable prism]. AB - A new compact and convenient prism consisting of a planoconvex and a planoconcave cylindrical lens varies continuously in strength between 0 and 90 prism diopters. The relationship between the angle of incidence and the prism dioptric power is discussed. PMID- 1299576 TI - [The 1987 National Epidemiological Survey of Blindness and Low Vision in China]. AB - According to the 1987 National Epidemiological Survey of Blindness and Low Vision, the prevalence of blindness in China was 0.43%, resulting chiefly from cataract (41.06%), corneal diseases (15.38%), trachoma (10.87%), and glaucoma (8.80%); the prevalence of low vision was 0.58%, of which the main causes were cataract (49.83%), ametropia/amblyopia (14.98%), trachoma (9.55%), corneal diseases (8.48%), chorioretinal diseases (6.27%), etc. Among children under 14 years of age, the leading cause of blindness and low vision was hereditary diseases (48.46%), and among the elderly of 60 years and over, the leading cause of blindness and low vision was cataract (73.13%). PMID- 1299577 TI - [An epidemiological survey and treatment of blindness in Kaipin County of Guangdong Province]. AB - An epidemiological survey of blindness was carried out in Kaipin County of Guangdong Province during October 1989 to May 1990, by stratified random cluster sampling. The sample population was 11,588, and the rate of blindness was 0.216%. The prevalence of blindness in persons aged 60 years and over was 48 times those of all other age groups combined. Since cataract accounted for 64% of the total blind cases, hence it was the key objective for surgical restoration of vision. Among 109 patients who were operated on for cataract, 83 cases were re-examined a half year later, and 78 cases (94%) had vision over 0.05. PMID- 1299578 TI - [Analysis of 10,686 cataract operations in Guangdong Province]. AB - Among 10,686 cataract operations performed in Guangdong province from 1988 to 1989, 80.16% of the patients were over 55 years of age, the ratio of female to male was 1.37:1, and 53.76% were peasants, mostly little educated. Blindness was unilateral in 55.46%, bilateral in 38.83%, and low vision in 5.71%. The mode of operation was intracapsular in 68.83%, extracapsular in 25.77%, and couching in 0.52%. After operation, 50.20% of the patients were restored useful vision, and 45.25% saved from disablement, the total success rate being 95.45%. 2.13% were ineffective and 2.14% had complications. The curative effects were up to the standards stipulated by the National Federation of Disabled Persons. PMID- 1299579 TI - [Feasibility of the new WHO Trachoma Grading System in China]. AB - The New WHO Trachoma Grading System is found feasible in China by an epidemiological survey of trachoma using the two trachoma grading systems, the new WHO system and the Chinese conventional system, especially for large scale examination and treatment and for epidemiological survey. However, the New System regards the proportion of active trachoma amongst children under 10 years as the index of the scope and severity of the disease in a community, while the authors opine that the trachoma prevalence in teenagers, especially in middle school students, better reflects the situation of trachoma infection in a Chinese community. PMID- 1299580 TI - [Application of the new trachoma grading system of WHO]. AB - The new trachoma grading system of WHO was followed in an epidemiologic survey of a rural sample population of 2,728 in Pingyin County, Shandong Province. The prevalence of trachoma was found to be 9.60%, and in children under 10 years of age, 3.69%. Trachoma was related with age; the rates of trachomatous inflammation intense (TI), trachomatous scarring (TS), trachomatous trichiasis (TT) and corneal opacity (CO) all increased with aging. The epidemiologic significance of the grading system was discussed. PMID- 1299581 TI - [The relationship between reading rehabilitation and visual functions in low vision]. AB - Reading rehabilitation was done for 51 low vision patients who underwent tests of the contrast sensitivity function (CSF) and the visual field. The results showed that the recognized frequency of CSF was related to the reading capability. The CSF was useful in predicting the reading prognosis, and visual field impairment significantly affected the reading ability. The relationship between the reading rehabilitation and the visual functions was discussed. PMID- 1299582 TI - [Changes in PVEP in primary open angle glaucoma and analysis of the waveform index]. AB - Black-white and color checkerboard pattern reversal VEP of 31 glaucomatous, 58 glaucoma suspect and 63 normal eyes showed that in the former two groups the mean latency of PVEP was lengthened significantly, and the waveform was flattened and widened. For quantification of the waveform changes, the authors proposed the waveform index, which diminished in the glaucomatous eyes. The detection rates of abnormal PVEP in the glaucoma and glaucoma suspect groups were significantly higher than in the normals. With color checkerboard stimulation of low luminance, the reduction of waveform index was even more obvious, especially with the blue/black checkerboard. PMID- 1299583 TI - [Modern extracapsular extraction for cataract of uveitis]. AB - Cataract of uveitis is difficult for extracapsular extraction (ECE) because of posterior synechiae. 21 cases (24 eyes) of the cataract were performed modern ECE with satisfactory results. Postoperative visual acuity was 0.1 or better in 20 eyes, and 0.5 or better in 7 eyes. The optimal time for the operation and the procedures were discussed. The authors opined that removal of the cataract could prevent recurrences in some severe refractory cases of uveitis. PMID- 1299584 TI - [Anterior segment fluorescein angiography and IOL implantation]. AB - Fluorescein leakage into the anterior chamber (AC) and from the iris were found early after extracapsular cataract extraction (8 eyes) and IOL implantation (29 eyes). The leakage into AC and from the iris were apparently comparable after ECCE, whereas the former was stronger after anterior or posterior chamber IOL implantation, and no leakage was discernible where the iris and the loops of AC IOL were in contact. Fluorescein leakage into the AC and from the iris indicated overall traumatic damage to the blood-aqueous barrier. PMID- 1299585 TI - [Treatment of dissociated vertical deviation (DVD) with superior rectus recession and posterior fixation suture]. AB - 19 cases (32 eyes) of DVD were treated with superior rectus recession and posterior fixation suture; the effective rate was 84%. The indications and the surgical procedures are described, and the postoperative complications and criteria for evaluation of therapeutic effects are discussed. PMID- 1299586 TI - [The hemorheological features and other related factors in patients with primary open angle glaucoma (POAG)]. AB - The second part of the investigation revealed that POAG patients manifested abnormalities in plasma viscosity, whole blood apparent viscosity and viscoelasticity, hematocrit, and mean red cell volume, with concurrent reduction in oxygen partial pressure degree of oxygen saturation, and levels of trace elements Cr, Zn, Mg, and Fe. The hemorheological factors should be taken into account in addition to intraocular pressure in the development of visual damages. PMID- 1299587 TI - Prediction of human pharmacokinetics of panipenem, a new carbapenem antibiotic, from animal data. AB - The prediction of human pharmacokinetics of Panipenem (PAPM), which is a new carbapenem antibiotic, was investigated using animal data. The plasma concentration-time curve after intravenous administration of PAPM in each animal showed biexponential elimination. There were good allometric correlations between pharmacokinetic parameters (CLtotal and Vd,ss) calculated from the plasma concentration in animal species and body weight of experimental animals. Predicted human pharmacokinetic parameters calculated by these allometric equations agreed with the values observed in humans. PMID- 1299588 TI - Interaction of aminoglycoside antibiotics and lithium at the neuromuscular junctions. AB - Lithium in the form of the carbonate or citrate salts has been used by Cade in 1949 for the treatment of affective disorders. Lithium is known to reduce the supply of inositol, the key substrate for the phosphoinositide cascade, by inhibiting some of the enzymes which hydrolyse the inositol phosphates. On the other hand aminoglycoside antibiotics are used extensively in the treatment of life-threatening infections despite their three important toxicities on kidney, ear and neuromuscular junctions. It has been suggested that aminoglycoside antibiotics inhibit the signal-transduction pathway by interaction with the inositol polyphospholipids, thereby inhibiting the production of second messenger molecules. In 1977 two case reports described prolonged neuromuscular blockades, one following succinylcholine and the other after pancuronium in patients receiving lithium therapy. The following investigation was undertaken to determine whether lithium interferes with aminoglycoside antibiotics (gentamycin and amikacin) at the neuromuscular junctions. The neuromuscular blocking effect of aminoglycoside antibiotics were tested in the isolated phrenic nerve hemidiaphragm preparation of the rat. The IC50 of gentamycin and amikacin were 1.75 and 5.27 mmol.l-1 respectively. Thereafter sodium chloride of the media was partially replaced by lithium chloride and the effect of gentamycin (1.75 mmol.l 1) and amikacin (5.27 mmol.l-1) were studied in this media. Incubation of the preparation by 0.5, 1.5 and 5.0 mmol.l-1 lithium 30 min before the use of antibiotics reduced the neuromuscular blocking effect of gentamycin and amikacin significantly. It appears that the prevention of the antibiotic-induced neuromuscular blockade by lithium observed in this study may be due to the changes of release of acetylcholine at the neuromuscular junctions. PMID- 1299589 TI - Prevention and control of surgical infections. AB - Surveillance and control of hospital infections are two particularly important aspects of the surgical ward, and great activity is necessary in the identification and the elimination of the risk factors whenever possible. Today the rational use of antibiotics, in both the prevention and treatment of infections, should be used to avoid or limit nosocomial infections, and it is as important as the use of disinfectants. Cefotetan has been studied in different surgical specialties in prophylaxis and treatment of postoperative infections for its particularly broad spectrum of activity, covering both aerobic and anaerobic organisms, and for the very low incidence of side-effects. In general surgery, Cefotetan has proved able to reduce not only the occurrence of surgical wound infections, but also that of postoperative infections of the genitourinary system. PMID- 1299590 TI - Captopril and glutathione before thrombolysis in acute myocardial infarction: a pilot study. AB - This study is aimed at checking whether treatment with glutathione (GL) and captopril (CA) before thrombolysis can further improve the protective effects of ACE-inhibitors in cases with anterior acute myocardial infarction (AMI). Ninety eight double blind randomized patients (86 men and 12 women) showing symptoms of AMI anterior and undergoing thrombolytic treatment were admitted to our study and subdivided into 4 groups. Group A (25 pts) received thrombolytic treatment only, Group B (23 pts) received 3 g GL intravenously 15 min before thrombolysis and for 2 h thereafter, Group C (26 pts) received 6.25 mg CA orally 15 min before starting thrombolytic treatment, Group D (24 pts) received 3 g GL intravenously before thrombolysis and for 2 h thereafter, and captopril as well like group C. On the third day after AMI onset groups A and B received CA also. In all groups, the doses of CA were gradually increased according to blood pressure values. The following features were considered: a) the occurrence of early (within the first 2 h after thrombolysis) ventricular hyperkinetic arrhythmias; b) CK peak; c) the normalization time of CK peak (NT); d) the occurrence of late ventricular hyperkinetic arrhythmias (VHA) in the predischarge Holter test (Lown's class 2); e) ejection fraction (EF) being measured in 60 pts undergoing haemodynamic test. The results were an follows: Group A: VHA early 13/25, CK peak 1982 +/- 282; NT 71 +/- 2 h; Late VHA 8/25; EF 53.5 +/- 2.5% (16 pts). Group B: VHA early 11/23; CK peak 1917 +/- 242 U/l; NT 69 +/- 3 h; late VHA 7/23; EF 54.5 +/- 5.4% (14 pts). Group C: VHA early 4/26; CK peak 1671 +/- 266 U/l; NT 58 +/- 3 h; late VHA 5/26; EF 55.5 +/- 3% (16 pts). Group D: VHA early 3/24; CK peak 1463 +/- 201; NT 56 +/- 4 h; late VHA 5/24; EF 57.6 +/- 4% (14 pts). PMID- 1299591 TI - [Research on autism. Different aspects of changes observed during the development period]. AB - Research on infantile autism in child psychiatry refers mainly to a concept of "non-change" and not so much to a concept of "change". Very few investigations included longitudinal perspectives. Even commonly used classifications (e.g., DSM III-R) did not consider developmental aspects. However, if we want to find better treatment approaches to help autistic children, we should try to elucidate basic developmental mechanisms concerning behavioral, biological, psychological and social factors taking into account both a concept of "change" and one of "non change". Having in mind both the relationship between brain function and developmental psychopathology as well as the possible interaction of the two developmental concepts mentioned above, the article first clarifies terms related to maturation in children like "absolute change" (e.g., intraindividual growth) and "relative change" (e.g., growth relative to the age group). In addition, the existence of a so-called after-maturation of the CNS (i.e., absolute and relative "change") in psychiatric disordered children is illustrated by the author's neurophysiological research. In contrast, an example of absolute "change" and relative "non-change" of electrical brain activity is given, i.e., power spectra of a child are like fingerprints. Furthermore, two kinds of maturational problems are discussed (developmental deviation versus developmental retardation). On the basis of these informations, the author refers to the main topic, namely, the relationship between central nervous maturation and behavior in autistic children. It is suggested, that recent imaging techniques and progress in EEG analysis should lead to new efforts in order to further investigate the question of lateralization deficits and its relation to language problems in autistic children during their development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299592 TI - [P 300 slow potential. Clinical interest in 3 mental diseases and neurobiology: a review]. AB - P300 is a late component of evoked potential which meet special relevance to the study of cognitive processes. P300 indexes categorization processes and the context updating of memory. Its latency reflects the stimulus evaluation time, and P300 amplitude is related to some psychological variables such as expectancy, attention and stimulus significance. In this review, clinical correlation between P300 components and mental diseases are reported, especially dementia, schizophrenia and depression. Delayed P300 latency has been found in Alzheimer disease and in other forms of dementia. Reduced P300 amplitude as well as altered topography has been reported in schizophrenia. In depression, reduced P300 amplitude has been related with longer reaction time. Unfortunately, the diagnosis utility of P300 seems limited. The authors also propose an overview of the actual knowledge on neurobiological findings in the generation of the P300 wave. Anatomical data point out the importance of the limbic system, more specifically, of the hippocampus and the locus coeruleus, in generating and modulating P300 wave. Data from the literature on the psychopharmacological modifications induced by cholinergic, catecholaminergic and other agents, are reviewed. Although the dopaminergic and noradrenergic systems are of some importance, these data emphasise the importance of the cholinergic system for the generation and modulation of P300 amplitude and latency. The value and interpretation of these neurobiological and clinical findings are discussed. PMID- 1299593 TI - [Study of Beck's hopelessness scale. Validation and factor analysis]. AB - The validation study and factorial analysis of the Beck's hopelessness scale is presented. Two groups were compared including patients suffering from depression (n = 100) and a control group (n = 93). Age and sex were comparable in the two groups. The hopelessness scale is valid, and differentiates depressive patients from control subjects. The scale has a good reliability (test-retest, r = .81) and a good internal consistency (alpha = .97) for depressive subjects and alpha = .79 for control subjects). It also shows a good concurrent validity with other scales assessing depressive cognitions, the automatic thoughts questionnaire, the dysfunctional attitudes scale (form A) and a scale assessing the suicidal risk (ERSD). No concurrent validity is found with scales assessing the intensity of depression, the Beck depression inventory and the Hamilton scale. The factorial analysis elicits a general factor, accounting for 38.15% of the variance, and reflecting negative feelings about the future. The study of all the factorial analysis shows the stability of the factorial structure. PMID- 1299594 TI - [Study of P 300 in schizophrenia. Some reflexions on methodological difficulties]. AB - We underscore the methodological difficulties in studying cognitive evoked potentials in schizophrenic patients. The main difficulties of such a study include the interruption of medication, the need of cooperation and immobility of subjects during the recordings, as well as of a correct patient-control matching for motivation, intellectual quotient, social and cultural levels. To establish correlations between clinical symptomatology and P 300 amplitude and latency we used both the DSM III-R and clinical rating scales. Clinical and electrophysiological testing must be performed the same day and have an excellent interrater agreement. Otherwise correlations are not reliable. Use of small patient samples is one major drawback which prevents to draw definitive conclusions. These difficulties usually unsaid are inherent to research in biological psychiatry and may partially explain the heterogeneity of results in the literature. PMID- 1299595 TI - [A scale to assess psychasthenia]. AB - "Psychasthenia exists--we meet it every day". Despite this affirmation, Pierre Janet's views remain unappreciated by international psychiatry. Psychasthenia is not included in the Diagnostic and Statistical Manual of Mental Disorders (DSM III-R). This pathology, described by Janet as both benign and terrible, is presently broken into many diagnostic categories with respect to the principal symptomatology of the patient. When a mood disorder is present, these patients can have diagnostic criteria for major depression or dysthymia. Patients with prevalent anxiety, phobia or obsessive-compulsive symptoms, must also be classified in having anxiety disorders. When somatic complaints are major symptoms, the patient's disease can be, on the whole, attributed to a somatoform disorder. This scale is a global evaluation of psychasthenia. It is made up of three lists of items. The first concerns asthenia or fatigue sine materia. The items in this group allow an evaluation of the physical and mental characteristics of asthenia associated with an inability of acting. Difficulties in mental concentration are measured by items in the second list. Mental processes are associated with doubts and waverings. They are interrupted by interferences caused by obsessions with recurrent and persistent ideas, impulses or images. Physical symptoms without organic pathology or a pathophysiologic mechanism constitute the neurasthenic part of psychasthenia. In the third list, somatic complaints are spelled out in a check-list of these potential symptoms. This scale can be used as a help in the diagnosis. Items 2, 3, 5, 25, 26 and 29 have a specific reference to the history of the disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299596 TI - [Withdrawal syndrome from antidepressive drugs. Report of 5 cases]. AB - Antidepressant withdrawal symptoms, following abrupt or gradual discontinuation of antidepressants, include general somatic distress (flu-like syndromes, gastro intestinal disturbances, myalgias, headache, chills, weakness and rhinorrhea), anxiety, agitation, sleep disturbances, movement disorders, cardiac arrhythmias, delirium and manic reactions. Two cases of delirium, an hypomanic reaction and two general distress and movement disorders are reported. Cases 1 and 2 required admission to a general hospital. The etiology of the delirium was difficult to assess as long as the clinicians did not know that patients were taking antidepressants. Case 3 corresponds to the paradoxical activation following antidepressant interruption. Cases 4 and 5 constitutes light withdrawal syndromes. Most of cases are probably unrecognized. These cases reflect the importance in daily practice of the phenomena. It can be concluded from our study that: antidepressants must not be abruptly discontinued when a somatic disease appears. When a patient treated with a psychotropic drug develops delirium, the withdrawal of antidepressant must be suspected and the prescribing physician contacted to know what kind of psychoactive medication was prescribed. PMID- 1299598 TI - [The prevention of blindness--past, present and future]. AB - Prevention of blindness is the most important aim of ophthalmology. Prevention of blindness is related to many factors. It is related to many factors, such as science and technology, economy and social behavior. There are worldwide activities by WHO, NGOs and other functions to promote the prevention of blindness in the world. More than 90% of blind population lives in developing world. Cataract is the top causes of blindness which is curable. Onchocerciasis is an endemic disease in west Africa and central America. Onchocerca Control Project (OCP) was formed in 1974 under WHO for the control of onchocerciasis by the funds of developed countries. The control of vector (simulium) as well as new drug are giving the the project the prospect of success in eradicating the disease, thus preventing the blindness by diseases. The situation on blindness by trachoma, childhood blindness, glaucoma, diabetes will be discussed. The progress of molecular genetics of eye disease may open the gate for prevention of blindness by these disease in future. PMID- 1299597 TI - [Comparative study of the efficacy and acceptability of amineptine and fluoxetine in patients with major depression]. AB - We compare two anti-depressant drugs, amineptine and fluoxetine, in a multicentric study. Amineptine is a dopamine reuptake inhibitor, and fluoxetine a serotonin reuptake inhibitor. Eighteen french centers participate in the study. One hundred and sixty nine outpatients were randomly assigned to either 200 mg of amineptine or 20 mg of fluoxetine during 90 days. They fulfilled the DSM III-R criteria of major depressive disorder. They were aged from 18 to 70. Minor tranquilizers were allowed during the study. The patients were evaluated at D0, D7, D21, D42 and D90. If possible, an additional evaluation was made at D4. Clinical evaluations included Clinical Global Investigation (CGI), Montgomery and Asberg Depressive Rating Scale (MADRS), HARD scale, Widlocher Retardation rating scale and Hopkins Symptom Check-list (HSCL). Somatic concerns were recorded at each visit. Among the 169 patients included in the study, only 141 ended it at D90. The two drugs had good antidepressive efficacy which was noticed as soon as D7 up to D90. If we compare the antidepressant activity, no statistical differences could be observed between the two drugs using different scales. The percentage of patients with an improvement of at least 50% of the global score at MADRS was 8.3% at D7; 41% at D21, 69.2% at D42 and 83.2% at D90 for the amineptine group. For the fluoxetine group, these percentages were, 7.7%; 37.8%; 78.9%; 82.1%. No statistical differences could be noticed between the two groups, and at any time of the study. We have tried to look for a rapid antidepressive action by a clinical evaluation at D4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299599 TI - [Epidemiology of glaucoma in Asia-Pacific]. AB - Primary open angle glaucoma is the second most important cause of permanent blindness in the Asia-Pacific region. Thus it is very important to identify epidemiological and other risk factors which are associated with open angle glaucoma. The risk for glaucoma optic nerve damage increases with the age and with the level of the intraocular pressure. In this paper, I will highlight our study of several risk factors for development of the open angle glaucoma like (1) elevated intraocular pressure, (2) myopia, (3) suspicious large optic disc cup, (4) cupping with disc haemorrhages and (5) nerve fibre defect. The general and systemic conditions which are implicated as risk factors are (1) family history of glaucoma. (2) increase in age, (3) diabetes mellitus, (4) cardiovascular conditions like central retinal vein occlusion etc. (5) the endocrine disorders with increased thyroid and increased corticosteroids responsiveness in patients with glaucoma will be discussed. PMID- 1299600 TI - [The immunologic studies on experimental heterogeneous penetrating keratoplasty]. AB - Using the experimental model of chicken-rabbit penetrating corneal grafting, micro-whole-blood 3H-TdR incorporation and ELISA the authors dynamically observed the functional state of cellular and humoral immunities for 10 weeks after operation. The results showed, (1) In both the homogroup and the hetero-group, the transformational degree of lymphocytes in peripheral blood increased, most obviously in the 3rd or 4th week postoperatively. (2) In the hetero-group, specific anti-corneal antibody appeared obviously in the serum during 2-8 weeks postoperatively. Combined with morphologic observation, it has proved that: (1) The immune rejection is mainly cellular mediated immunoresponse, meanwhile, the humoral immunoresponse also participates in it, and the humoral immunoresponse participates in the heterokeratoplasty more obviously. (2) Applying the micro whole-blood 3H-TdR incorporation is capable of determining the immunologic state of the body after corneal transplantation. (3) Attention should be focused on the 3-4 week period postoperatively when immunosuppressive-agent is administered. PMID- 1299601 TI - [Secondary posterior chamber intraocular lens implantation]. AB - In 16 aphakic eyes (16 patients) with intact posterior capsule posterior chamber IOL implantation were performed. The average uncorrected vision prior to the operation was 0.06. Six months after the implantation the uncorrected vision of > or = 0.5 accounted for 62.5% with an average of 0.53, the corrected vision of > or = 0.5 accounted for 93.37% and that of > or = 1.0 accounted for 81.25%. The average preoperative density of corneal endothelium in the central area was 2,646/mm2, the average of density after the secondary implantation was 1,824/mm2. All but one patient achieved binocular vision postoperatively. No persistent corneal edema and uveitis were found. The results showed that secondary P. C IOL implantation in an aphakic eye with intact posterior capsule is effective and safe if the indications and techniques are well managed. PMID- 1299602 TI - [Studies on human gamma-crystallins. I. Quantitative changes with age and cataract formation]. AB - Water soluble protein from human lenses at various ages are separated by Sephadex gel chromatography. The results show that there are major three gamma-crystallins (gamma 1, gamma 2, gamma 3) in human lenses. In normal lenses the total contents of the three gamma-crystallins in water soluble fraction of lens proteins keep stable as age increases. However, among the three gamma-crystallins, gamma 1 increase and gamma 2 decrease markedly, and very little change with gamma 3 are found as age increases. In nuclear cataractous lenses, all three gamma crystallins decrease as compared with the normal lenses of the same age. The variety of synthesis of each gamma-crystallin is mainly responsible for the changes of their quantities. It is postulated that the total low molecular weight crystallin contents in water soluble proteins of the human lens is related to the transparency of lens. The structural characterization of gamma 3-crystallin is responsible for the relative constant as age increases. PMID- 1299603 TI - [Convergence insufficiency and asthenopia]. AB - 22 cases with convergence insufficiency (CI) were presented here. It is found that there was an important relationship between CI and asthenopia. The causes clinical findings, diagnostic criteria, treatment of CI and relation with asthenopia were discussed. PMID- 1299604 TI - [Microvitreoretinal surgery for management of giant retinal tears with posterior flat folded-over]. AB - Twelve cases (12 eyes) of giant retinal tears with posterior flat folded-over were treated using vitrectomy, membrane peeling, and air or silicone oil tamponade. The operations were successful in 4 of the 5 cases of silicone oil tamponade group and in 2 of the 7 cases of air tamponade group. All the successfully operated eyes (6 eyes) had a visual acuity of 0.05 or better. We believe that vitrectomy makes it possible for the folded-over and fixed retina to recover mobilization and return to its normal anatomic position. PMID- 1299605 TI - [Pathogenesis of traumatic proliferative vitreoretinopathy]. AB - Proliferative vitreoretinopathy is the main cause of loss of vision following posterior penetrating eye injury. Clinically, it can range from macular epiretinal membrane to total retinal detachment and phthisis bulbi. To gain more knowledge of its pathogenesis, the author performed morphologic studies using a primate model and also studied the distribution of fibronectin in 13 enucleated patient eyes using immunofluorescent histochemical techniques. Results indicate this disease process represents an overstimulated response to retinal injury. Posterior vitreous detachment at the level of internal limiting membrane appears to be a predisposing factor. During the active phase of the disease process, there is selective increase of fibronectin in the choroid. This increase is not merely due to the passive leakage of plasma caused by the injury, but the choroid itself produces cellular fibronectin. Fibronectin is known to enhance wound healing and may be an important factor in the pathogenesis of proliferative vitreoretinopathy. PMID- 1299606 TI - [The risk factors of proliferative vitreoretinopathy after operation of retinal detachment]. AB - 160 failure cases (160 eyes) following retinal reattachment surgery were reviewed. 62 cases with proliferative vitreoretinopathy were divided into proliferative vitreoretinopathy (PVR) group, the other cases (98 cases) without PVR changes were divided into NO PVR group. The clinical characteristics of two groups were compared in order to determine the risk factors in the development of server PVR after surgical repair of retinal detachment. The study shows that retinal detachment with uveitis and low tension, preoperative and post-operative vitreous hemorrhage, multiple operations were the highly significant risk factors. Once these factors existed simultaneously, the incidence of PVR increased. The way how to prevent and decrease the occurrence of PVR were suggested in the series. PMID- 1299607 TI - [Vitreous surgery for retinal detachment with severe proliferative vitreoretinopathy and probe of failed cause]. AB - Eighty-one cases (81 eyes) of retinal detachment with severe proliferative vitreoretinopathy were treated using vitrectomy, scleral buckling and air or silicone oil tamponade technique. After a follow-up period of 6-28 months, 54 cases obtained anatomic retinal attachment (66.7%). For the serious cases of PVR D3, we also gained a success rate of 50%. Vision improved in 50 cases, whereas 34 cases got a vision better than 0.05. For the failed cases, cause that prevent the retina from attachment was probed. We think that vitrectomy is an essential and important procedure for retinal detachment with severe PVR, membrane peeling is the key of success and prevention of reproliferation can avoid recurrent retinal detachment and further raise the success rate of treatment. A new classification is recommended in this article. PMID- 1299608 TI - [Micro-vitreoretinal surgery for failed common retinal detachment repair]. AB - In this paper we analyzed 49 cases (49 eyes) of micro-vitreoretinal surgery for failed common retinal detachment repair. Reattachment was achieved in 37 cases (75.51%) and final visual acuity of 10/200 or better was attained in 32 cases (65.31%). It was suggested that common operation failure in these patients was due to PVR. Cryopexy, diathermy and repeat operation can render the formation of the PVR. Micro-vitreoretinal surgery should be performed on these patients. There was a linear relationship between the effectiveness and the degree of PVR. It is best to perform the surgery 3 months after common operation. Finally, the authors discuss the reasons for failure of vitreoretinal surgery and conclude that the anterior PVR and the invalid fixing are the main reasons for failure of vitreoretinal surgery. PMID- 1299609 TI - Characterisation of a near infra-red absorption band of the Escherichia coli quinol oxidase, cytochrome o, which is attributable to the high-spin ferrous haem of the binuclear site. AB - The bacterial quinol oxidase, cytochrome o, is an enzyme which is highly analogous to the better known cytochrome c oxidase, cytochrome aa3, but with the important difference that it lacks the near infra-red absorbing pigment CuA. In this article we report an absorption band in the near IR spectrum of cytochrome o with a maximal absorption at 758 nm, and which is attributable to the ferrous high-spin haem. The 758 nm band has an extinction coefficient of 0.2-0.3 mM-1.cm 1 at 758-800 nm. This region in cytochrome aa3 is dominated by the CuA absorption. The 758 nm absorption is lost on addition of CO or cyanide to the reduced enzyme. The carbon monoxide compound of cytochrome o also has absorbance bands in the near infra-red, and these may be attributable to a low-spin ferrous haem compound. PMID- 1299610 TI - A relationship between the starting secondary structure of recombinant porcine growth hormone solubilised from inclusion bodies and the yield of native (monomeric) protein after in vitro refolding. AB - Recombinant porcine growth hormone (rPGH) was solubilised from inclusion bodies (IB's) using either 6 M guanidinium hydrochloride (GnHCl), 7.5 M urea or by a novel method using a cationic surfactant, cetyltrimethylammonium chloride (CTAC). Circular dichroism (CD) analysis of the secondary (2 degrees) structure of the urea- and GnHCl-solubilised rPGH showed the absence of alpha-helical content with the majority of the molecule existing in a 'random coil' structure. In contrast, the CTAC-solubilised rPGH displayed significant starting 2 degrees structure (10 15% alpha helix; 30-40% beta structure). The three rPGH preparations were refolded in vitro against weak urea. GnHCl or aqueous buffers, resulting in an average refolding efficiency of 50% native (monomeric) rPGH for CTAC solubilised IB's and only 20% for urea or GnHCl solubilised IB's. We conclude that the method of solubilisation of IB's and the resultant difference in the starting 2 degrees structure of rPGH, particularly alpha-helical content, is a major in vitro factor that apparently predetermines the aggregation/refolding behaviour rPGH irrespective of refolding environment. PMID- 1299611 TI - The envelope glycoprotein of Ebola virus contains an immunosuppressive-like domain similar to oncogenic retroviruses. AB - Genomic RNA of a Zaire strain of Ebola virus was cloned, and cDNA inserts specific for the glycoprotein gene were isolated and sequenced. The determined sequence has only one open reading frame encoding 318 amino acids and is part of ORF-4 on the plus RNA strand. The putative transcriptional stop site (3' AAUUCUUUUU 5') and the transcriptional start site (3' AACUACUUCUAAUU..5') were identified. Computer-assisted comparison of the amino acid sequence of the C terminal part of protein encoded by ORF-4 of Ebola virus with sequences of the proteins present in the SWISSPROT and EMBL banks revealed significant homology with the 'immunosuppressive domain' of the p15E envelope proteins of various oncogenic retroviruses. The possible role of such a homology is discussed. PMID- 1299612 TI - Interaction between oleic acid-containing pH-sensitive and plain liposomes. Fluorescent spectroscopy studies. AB - The energy transfer method has been applied to study the interaction between pH sensitive liposomes (phosphatidyl ethanolamine/oleic acid/cholesterol, 4:2:4 molar ratio) and plain liposomes (phosphatidyl choline/phosphatidyl ethanolamine/cholesterol, 4:2:3 molar ratio). It was shown that a slow fusion process occurs between two types of liposomes. Also, the transfer of oleic acid from pH-sensitive liposomes to plain liposomes takes place. This transfer results in the increased permeability of both pH-sensitive and plain liposomes, facilitating the release of liposome-entrapped fluorescent dye. The data obtained were used for a possible explanation of the mechanism of intracytoplasmic drug delivery by pH-sensitive oleic acid-containing liposomes. PMID- 1299613 TI - Isolation of a new ligand-carrying casein fragment from bovine mammary gland microsomes. AB - Whilst looking for components involved in retinol metabolism in secreting mammary gland cells, a 12 kDa protein was isolated. This protein had bound a ligand with characteristics of retinol. N-Terminal sequencing and amino acid analysis showed that this protein is highly homologous with an alpha-s1-casein fragment. No ligand was found for beta-lactoglobulin, previously thought to be involved in retinol metabolism. PMID- 1299614 TI - Phosphorylation of vascular smooth muscle caldesmon by endogenous kinase. AB - Caldesmon was phosphorylated up to 1.2 molPi/mol using a partially purified endogenous kinase fraction. The phosphorylation site was within the C-terminal 99 amino acids. We were also able to phosphorylate caldesmon incorporated into native and synthetic smooth muscle thin filaments. Phosphorylation did not alter caldesmon binding to actin or inhibition of actomyosin ATPase. It also did not change Ca2+ sensitivity in native thin filaments. Phosphorylated caldesmon bound to myosin less than unphosphorylated caldesmon, especially when the myosin was also not phosphorylated. This work did not support the hypothesis that caldesmon function is modulated by phosphorylation. PMID- 1299615 TI - Relationship between membrane lipid mobility and spectrin distribution in lymphocytes. AB - We have previously established that T and B lymphocytes in situ are remarkably heterogeneous with respect to the cytoskeletal protein spectrin. Since in erythrocytes spectrin is known to play an important role in the regulation of membrane fluidity, lipid organization and lateral mobility of membrane proteins, we have sought to determine if the heterogeneous patterns of spectrin distribution that we have observed are related to possible differences in membrane lipid organization in these various subsets. To this end, we have utilized a fluorescent pyrene-labelled phospholipid as a probe of the lipid lateral mobility and have examined two related T cell systems maintained in vitro, DO.11.10 cells and a spontaneously arising variant, DO.11.10V. In these (and other cloned in vitro systems) we have previously observed that the cells homogeneously express one of the kinds of spectrin distribution patterns observed in situ. Thus the uniformity of staining of these systems permits us to address whether the various patterns of spectrin distribution may be predictive of differences in membrane lipid properties. Here we show that in cells in which there is little or nor spectrin at the plasma membrane (DO.11.10) that the lipids in the plasma membrane are considerably less mobile than in its related variant in which spectrin is diffusely distributed within the cell and at the plasma membrane. From this and previous results, we conclude that differences in the distribution of the cytoskeletal protein spectrin among lymphocytes may be a useful parameter in helping to predict the status of membrane lipid organization. PMID- 1299616 TI - Observation of the FeIV=O stretching Raman band for a thiolate-ligated heme protein. Compound I of chloroperoxidase. AB - The FeIV=O stretching vibration has never been identified for a cysteine coordinated heme enzyme. In this study, resonance Raman and visible absorption spectra were observed simultaneously for transient species in the catalytic reaction of chloroperoxidase with hydrogen peroxide by using our original apparatus for mixed-flow and Raman/absorption simultaneous measurements. For the first intermediate, the FeIV=O stretching Raman band was observed at 790 cm-1, which shifted to 756 cm-1 with the 18O derivative, but the v4 band was too weak to be identified. This suggested the formation of an oxoferryl porphyrin pi cation radical. The second intermediate gave an intense v4 band at 1,372 cm-1 but no oxygen isotope-sensitive Raman band, suggesting oxygen exchange with bulk water. PMID- 1299618 TI - Identification of a membrane-associated 1-0-alkyl-2-arachidonoyl-sn-glycero-3 phosphocholine hydrolyzing phospholipase A2 in guinea pig 1 epidermis. Implications in the cutaneous biosynthesis of platelet-activating factor. AB - A membrane-associated 1-0-alkyl-2-arachidonoyl-GPC hydrolyzing phospholipase A2 was identified in guinea pig epidermis. It is regio-specific (associated with the particulate microsomal fraction) and specific for the hydrolysis of 1-0-alkyl-2 arachidonoyl-sn-glycero-3-phosphocholine. It is sensitive to low calcium concentrations suggesting that it may be activated by increasing intracellular calcium. Since ether-linked phospholipids are known to exist in the epidermis, further understanding of the properties of this 1-0-alkyl-arachidonoyl hydrolyzing PLA2 may allow us to control the generation of 1-0-alkyl-2-lyso-sn glycero-3-phosphocholine, a key substrate for the generation of the platelet activating factor in the tissue. PMID- 1299617 TI - Phorbol ester-induced redistribution of the ASGP receptor is independent of receptor phosphorylation. AB - Like virtually all endocytic receptors, the human asialoglycoprotein (ASGP) receptor is phosphorylated by protein kinase C at serine residues within the cytoplasmic domains of its two subunits H1 and H2. Activation of protein kinase C by phorbol esters results in hyperphosphorylation and in a concomitant net redistribution of receptors to intracellular compartments (down-regulation) in HepG2 cells. To test whether there is a causal relationship between receptor hyperphosphorylation and redistribution, we examined the effect of phorbol ester treatment on the ASGP receptor composed of either wild-type subunits or of mutant subunits lacking any cytoplasmic serine residues in transfected NIH3T3 fibroblast and COS-7 cells. Although the wild-type subunits were hyperphosphorylated in fibroblast cells, the distribution of neither the wild-type nor the mutant receptors was affected. In contrast, phorbol ester treatment of transfected COS-7 cells induced down-regulation of both wild-type and mutant receptors. These findings indicate that redistribution of the receptor is independent of its cytoplasmic serines and is not caused by receptor phosphorylation. PMID- 1299619 TI - Specific binding of CAP-50 to calcyclin. AB - CAP-50, a calcyclin-associated protein with an apparent molecular mass of 50 kDa, was purified and proved to be a novel annexin [Tokumitsu, H. et al. (1992) J. Biol. Chem. 267, 8919-8924]. We examined the binding of CAP-50 to other Ca(2+) binding proteins which have two of four EF-hand structures, by a co-precipitation assay with phospholipid (phosphatidylserine). Among nine Ca(2+)-binding proteins (calcyclin, S-100 proteins, p11, calgizzarin, calvasculin, calmodulin and troponin C) examined, only calcyclin interacted with CAP-50. These results clearly show that the interaction of CAP-50 to calcyclin is specific, i.e. other Ca(2+)-binding proteins with the EF-hand structure could not substitute for calcyclin, thereby suggesting the possible role in specific regulation of the function of CAP-50 by Ca2+/calcyclin. PMID- 1299620 TI - De-novo biosynthesis of chlorinated aromatics by the white-rot fungus Bjerkandera sp. BOS55. Formation of 3-chloro-anisaldehyde from glucose. AB - The white-rot fungus Bjerkandera sp. BOS55 produced de-novo several aromatic metabolites. Besides veratryl alcohol and veratraldehyde, compounds which are known to be involved in the ligninolytic system of several other white-rot fungi, other metabolites were formed. These included anisaldehyde, 3-chloro-anisaldehyde and a yet unknown compound containing two chlorine atoms. Additionally GC/MS analysis revealed the production of small amounts of anisyl alcohol and 3-chloro anisyl alcohol. After 14 days, the extracellular fluid of Bjerkandera BOS55 contained 100 microM veratraldehyde and 50 microM 3-chloro-anisaldehyde. This is the first report of de-novo biosynthesis of simple chlorinated aromatic compounds by a white-rot fungus. Anisaldehyde and 3-chloro-anisaldehyde were also produced by Bjerkandera adusta but not by Phanerochaete chrysosporium. PMID- 1299621 TI - Evidence of a tertiary interaction functional in group I 3'-splicing. AB - It has been recently shown that the schedule of 3'-splicing events for yeast mitochondrial group I introns requires that conserved helix P10 materializes only after 5'-cleavage has taken place. A scenario compatible with experimental findings has been proposed [(1992) FEBS Lett. 297, 201-204; (1990) Proc. Natl. Acad. Sci. USA 87, 8192-8196] where the formation of P10 is postponed by competition for standard base-pairing with an extended P1 interaction engaging the same portion of the internal guide sequence (IGS) which is subsequently involved in P10. Although the formation of P10 in the fifth intron of yeast apocytochrome b gene (YCOB5) has been confirmed by site-directed mutagenesis, we cannot be confident that this interaction is merely stabilized by Watson-Crick base-pairing, involving the 3'-exon and the IGS, especially given that its formation requires closure of an intron loop of 159 unpaired bases. Thus, our aim is to establish the participation of the 5'-extremity of the intron in the formation of P10. By deoxyribose substitution at positions 1 and 2 of the 5' extremity of the intron, we are able to confirm the existence of tertiary interactions stabilizing the 3'-splicing site. We show that selective deoxyribose substitution renders the intron inefficient for 3'-splicing when compared with wild type levels. PMID- 1299622 TI - Parathyroid hormone-related peptide can regulate the growth of human lung cancer cells, and may form part of an autocrine TGF-alpha loop. AB - Parathyroid hormone-related peptide (PTHrP) and transforming growth factor-alpha (TGF-alpha) were found to stimulate proliferation of human lung cancer cells (BEN 57). TGF-alpha stimulated PTHrP secretion from these cells. The polyclonal antisera raised against PTHrP significantly inhibited the growth of BEN-57 cells, and also the proliferation induced by TGF-alpha. Treatment of cells for up to 10 days with either a PTHrP receptor antagonist (PTHrP(7-34)) or PTHrP antiserum significantly inhibited the subsequent growth of these cells. We suggest that PTHrP may be a component of a complex autocrine loop involving TGF-alpha. PMID- 1299623 TI - Interleukin-8 receptor-mediated chemotaxis of normal human epidermal cells. AB - Normal human keratinocytes show chemotactic behavior towards interleukin-8 (IL 8). Under physiological conditions this cytokine seems to be present in an equilibrium between monomeric and dimeric forms, as indicated by Western blotting data. Radioligand binding studies suggest that keratinocyte chemotaxis is mediated by receptors specific for IL-8 dimers. IL-8 receptor-specific mRNA can be detected in a keratinocyte cell line by polymerase chain reaction. PMID- 1299624 TI - Upstream activation element of the PH03 gene encoding for thiamine-repressible acid phosphatase in Saccharomyces cerevisiae. AB - The PH03 gene of Saccharomyces cerevisiae encodes thiamine-repressible acid phosphatase and requires the positively acting regulatory protein THI2 for its expression. Deletion analysis of the 5'-flanking region of PH03 gene revealed that an activating region located at nucleotide position -234 to -215 relative to the translation initiation codon is required for the expression and sensitivity to thiamine. A chemically synthesized DNA fragment covering -234 to -215 showed a significant level of expression when inserted in front of the PH03 promoter lacking the activating region. Electrophoretic mobility shift assay demonstrated the presence of proteins that bound to the above DNA fragment in the nuclear extract from cells grown in thiamine-free medium. These findings suggested that this region between -234 and -215 acts as an upstream activation element of the PH03 gene that can interact with regulatory proteins. PMID- 1299625 TI - Solubilization steps of dark-adapted purple membrane by Triton X-100. A spectroscopic study. AB - Ultraviolet-visible spectroscopy has been used to follow the solubilization of the dark-adapted purple membrane of Halobacterium halobium by Triton X-100. Turbidity of purple membrane fragments and absorbance of bacteriorhodopsin variations during continuous addition of detergent give solubilization profiles exhibiting several break points corresponding to different equilibrium stages of the solubilization process. The present method allows the determination of the detergent to protein+lipid ratio in mixed aggregates at the corresponding break points. It was concluded that, when performed systematically, this technique is a very convenient and powerful tool for the quantitative study of biomembrane-to micelle transition. PMID- 1299626 TI - Effects of apocynin, a drug isolated from the roots of Picrorhiza kurroa, on arachidonic acid metabolism. AB - Apocynin is a constituent of root extracts of the medicinal herb Picrorhiza kurroa and has been shown to possess anti-inflammatory properties. We investigated the effects of apocynin on the production of arachidonic acid derived inflammatory mediators by guinea pig pulmonary macrophages. Apocynin concentration-dependently inhibited the formation of thromboxane A2, whereas the release of prostaglandins E2 and F2 alpha was stimulated. Apocynin potently inhibited arachidonic acid-induced aggregation of bovine platelets, possibly through inhibition of thromboxane formation. The present results suggest that apocynin might, beside its therapeutic effects in inflammatory conditions when given in a root extract of P. kurroa, also be a valuable tool in the development of new anti-inflammatory or anti-thrombic drugs. PMID- 1299627 TI - Is thioredoxin the physiological vitamin K epoxide reducing agent? AB - E. coli thioredoxin plus thioredoxin reductase have previously been shown to replace dithiothreitol as the electron donor for mammalian liver microsomal vitamin K epoxide reduction in vitro. Such activity is dependent on detergent disruption of the microsomal membrane integrity. A previously characterized salicylate-inhibitable pathway for electron transfer from endogenous cytosolic reducing agents to the microsomal epoxide reducing warfarin-inhibitable enzyme is not inhibited by known alternate substrates and inhibitors of the thioredoxin system nor by antibodies against thioredoxin. PMID- 1299628 TI - Chlorpheniramine inhibits the ornithine decarboxylase induction of Ehrlich carcinoma growing in vivo. AB - The antihistaminic (+/-)-chlorpheniramine significantly reduced the progression of Ehrlich carcinoma when it was administered at 0.5 mg/mouse/day from the third day on, after tumour inoculation. The ODC activity of tumour cells was diminished by 70% on day 7 after tumour transplantation, when maximum ODC activity is detected in non-treated tumour growing 'in vivo'. Northern blot analyses indicated that the inhibitory effect of this 1,4-diamine takes place at a post transcriptional level. Results obtained from serum-free cultured cells indicated that chlorpheniramine inhibits the ODC synthesis rate. PMID- 1299629 TI - A 17.6 kbp region located upstream of the rabbit WAP gene directs high level expression of a functional human protein variant in transgenic mouse milk. AB - We have investigated whether DNA regions present in the rabbit whey acidic protein (WAP) promoter/5' flanking sequence could potentially confer, in vivo, high level expression of reporter genes. Transgenic mice were generated expressing a variant of human alpha 1-antitrypsin, which has inhibitory activity against plasma kallikrein under the control of a 17.6 kbp DNA fragment located upstream of the rabbit WAP gene. Up to 10 mg/ml of active and correctly processed recombinant protein were detected in mouse milk, thus suggesting that the far upstream DNA sequences from the rabbit WAP gene might be useful for engineering efficient protein production in the mammary glands of transgenic animals. PMID- 1299630 TI - Inference systems for automated image analysis. AB - The radiodiagnostic process is a complicated activity involving the integration of knowledge from low-level image features into more abstract, higher-order entities. This involves spatial and density information at a lower level and area and features at a higher level. The spatial density distribution in a radiographic image is not uniquely related to the three-dimensional structure of the object. Therefore, more information other than just first-order density characteristics of radiographs must be utilized to improve automated interpretation of the image. Prior knowledge of the size, shape and location of anatomical structures and pathognomic features is very useful for improving the process of computer-aided image analysis. Inference systems as used in expert systems can be applied to facilitate the integration of information obtained from the patient and the radiograph in the diagnostic process. PMID- 1299631 TI - An introduction to model-based imaging. AB - The purpose of this paper is to clarify the distinction between the recognition of form, i.e. pattern recognition, and the interpretation of visual scenes, i.e. image understanding. Pattern recognition is part of image understanding, but the latter also includes cognitive tasks such as learning and inference. The key to developing image-understanding systems is to concentrate on the representation and use of models. This paper is a brief outline of the components of a model based image-understanding system. First, the notions of iconic, categorical and symbolic knowledge are described. Although they appear to be disparate, the common notion is that the image understanding is based on recognizing concepts and not recognizing form. Next, the notion of a concept is defined, followed by representation techniques and control strategies for using concepts. Last, an example is given of an image-understanding system that learns to recognize concepts such as radiographic projections of teeth in panoramic radiographs. PMID- 1299632 TI - Application of computer-aided image interpretation to the diagnosis of periapical bone lesions. AB - An image analysis system was developed for the computer-aided diagnosis of periapical bone lesions in dental radiographs. The system was designed to (1) identify the periapical region, (2) determine the presence of a periapical lesion and (3) estimate the size of the lesion in cases when a lesion had been found. To initiate the procedure, an observer indicates an arbitrary point on the root in a digitized radiograph. From this initial point, the location of the radiographic projection of the apex of the root is automatically computed. Next, the trabecular bone pattern is detected through texture analysis. A local absence of the trabecular bone pattern in the periapical region is marked as a periapical bone lesion. When a lesion has been identified, its size is estimated based on local edge properties. Observer interaction is only allowed to adjust the result of the apex localization procedure if the apex has not correctly been localized. In an experiment with randomly selected radiographs of 111 mandibular roots, the performance of the system was tested against the consensual diagnosis of four expert observers. The sensitivity of the system to identify a lesion was 83.3%, the specificity 75.6% and the diagnostic accuracy 80.2%. The correlation between the size of the lesions as estimated by the system and by the observers was 0.67 (P < 0.01). When the procedure was repeated, the percentage of correctly reproduced lesion sizes by the system was 92.8%. The determination of the presence of a lesion was reproducible in 98.2% of all the cases. PMID- 1299633 TI - Computer-aided quality assurance in oral health care: the image of electronic radiographs. AB - The concept of a decision-support oriented, interactive, multimedia technique based dental workstation is presented from the viewpoint of improved quality assurance. Special emphasis is given to the modules for handling and interpretation of radiographs. PMID- 1299634 TI - Digital radiology in dental diagnosis: a critical view. PMID- 1299636 TI - Image processing for the evaluation of dental implants. PMID- 1299635 TI - Digital radiology for implant treatment planning and evaluation. AB - Digital radiology has provided the clinician with the ability to store and manipulate radiographic information. The purpose of this paper is to present two applications of digital imaging to implantology. The first application is a personal computer-based imaging technique which can be used to plan the placement of endosseous dental implants using three-dimensional computed tomography images obtained with commercial software. The second application uses digital subtraction radiography to assess longitudinal bony change around dental implants. PMID- 1299637 TI - Communication in digital radiology. AB - The long-distance transfer of dental radiographs was explored as early as the 1920s. The practicality of such image transfer has improved through advances in telecommunications and computer networks (both hardware and software) and the emerging trends towards direct and indirect digital imaging techniques for recording oral and maxillofacial radiographs. This paper reviews the current status of communication in digital dental radiology. It is illustrated by personal observations from a variety of demonstration projects. PMID- 1299638 TI - Design and implementation of an image management and communications system (IMACS) for dentomaxillofacial radiology. AB - An Image Management and Communications System for digital dentomaxillofacial radiology is under development at the Department of Dental Diagnostic Science at the University of Texas Health Science Center at San Antonio, Texas, USA. In its final stage, the system will provide a method of integrating different direct digital image acquisition modalities such as intraoral, panoramic and extraoral radiography. A review of the design criteria necessary for establishing such a system for clinical dentistry is discussed and the first phase of its implementation described. PMID- 1299639 TI - Effects of the Nd:YAG dental laser on plasma-sprayed and hydroxyapatite-coated titanium dental implants: surface alteration and attempted sterilization. AB - The Nd:YAG dental laser has been recommended for a number of applications, including the decontamination or sterilization of surfaces of dental implants that are diseased or failing. The effects of laser irradiation in vitro (1) on the surface properties of plasma-sprayed titanium and plasma-sprayed hydroxyapatite-coated titanium dental implants, and (2) on the potential to sterilize those surfaces after contamination with spores of Bacillus subtilis have been examined. Surface effects were examined by scanning electron microscopy, energy dispersive spectroscopy, and x-ray diffraction after laser irradiation at 0.3, 2.0, and 3.0 W using either contact or noncontact handpieces. Controls received no laser irradiation. Melting, loss of porosity, and other surface alterations were observed on both types of implants, even with the lowest power setting. For the sterilization study, both types of implants were first sterilized by exposure to ethylene oxide and then contaminated with spores of B subtilis. After laser irradiation, the implants were transferred to sterile growth medium and incubated. Laser irradiation did not sterilize either type of implant. The spore-contaminated implants in the control group were successfully sterilized with ethylene oxide. PMID- 1299640 TI - Comparison of stress transmission in the IMZ implant system with polyoxymethylene or titanium intramobile element: a finite element stress analysis. AB - Using the finite element method, this study modeled a 4.0 x 13.0-mm IMZ implant, restored with a cast gold crown, to examine the influence of the polyoxymethylene (POM) intramobile element (IME) on the transmission of vertical and oblique forces. Stress concentrations in the bone and in components of the implant system were much greater under a 30-degree load than under an equal vertical load. Stress transmission to bone occurred chiefly in the crestal region, and these stresses were not reduced when the IME was modeled in POM rather than in titanium. Maximum stress concentrations occurred in the fastening screw. PMID- 1299641 TI - Osseointegrated implants in the maxillary tuberosity: report on 45 consecutive patients. AB - Although the first and second molars usually are lost first in a partially edentulous maxilla, titanium implants are seldom placed more distally than at the second premolar site because of the poor quality of bone often found in the posterior maxilla. The present series encompasses 72 Branemark implants placed in the third molar-tuberosity area with a success rate of 93% and an average follow up after loading of 21.4 months. Moreover, two of the failed implants were in patients who had a simultaneous successful implant contralaterally. Keys to this high success rate include the meticulous identification and correction of all pathoses, modification of the drilling sequence to maximize initial implant stabilization, achievement of bicortical fixation whenever possible, gentle handling of the soft tissues and periosteum, and elimination or minimization of transmucosal occlusal loading during osseointegration and of nonaxial loading after connection. PMID- 1299642 TI - Comparison of impression techniques for a two-implant 15-degree divergent model. AB - To consistently provide passively fitting implant superstructures, an understanding of the accuracy and precision of all phases of fabrication and connection is required. The initial phase of fabrication, ie, impression making and cast forming, was investigated in an earlier report for a mandibular five implant model. The current study evaluates the accuracy of working casts produced from impressions using two different transfer copings in a 15-degree divergent two-implant posterior mandibular model. While the indirect method is less cumbersome to use, it was found to be less accurate in the prior study. The purpose of this study was to see if the direct method is more precise for this clinical situation. A transfer was deemed effective in producing experimental casts if distances between specified points on the cast agreed with the corresponding distances on the master cast. The absolute value of the difference in distances between experimental and master casts was compared for the two techniques (two-sample t tests). No significant differences were noted (P > .05), and the power of the tests ranged from 0.70 to 0.96 against the one-sided hypothesis that the direct method had a smaller mean absolute difference in distance than the indirect method. This suggests no clear advantage in using the direct method in similar clinical situations. Comparison of these findings to other impression accuracy studies is made. PMID- 1299643 TI - Tissue-integrated prosthesis complications. AB - Over a 78-month period from 1983 to 1990 at the Mayo Clinic, 353 patients involving 407 jaws were restored with 1,778 Branemark system implants supporting prostheses. Complications involved loss of implant anchorage, soft tissue problems, or mechanical problems. The most predominant complication involved soft tissues. There were 152 patients with loaded prostheses who had no complications and 37 with only one occurrence. Those seen in 160 patients with more than one occurrence were all conservatively managed, so that prosthesis use was only permanently discontinued in 4 patients, who returned to the use of a maxillary complete denture. PMID- 1299644 TI - A histomorphometric study of unthreaded hydroxyapatite-coated and titanium-coated implants in rabbit bone. AB - Hydroxyapatite-coated and titanium-coated IMZ dental implants were investigated in an animal study. The implants were placed in the distal femurs of rabbits. Six months after placement, histomorphometric evaluation of the bone-to-implant contact was conducted. The hydroxyapatite-coated specimens demonstrated significantly more direct bone contact compared to the titanium-coated controls. PMID- 1299645 TI - Histomorphometry of bone apposition around three types of endosseous dental implants. AB - Three different types of commercially available dental implants (Nobelpharma, IMZ, and Integral) were implanted in the edentulous mandibles of seven adult mongrel dogs. Twenty-one implants were harvested with block sections after 12 weeks and embedded in polymethyl methacrylate resin. Undecalcified sections were prepared with the sectioning-grinding technique. The percentage of bone contacting the implant surface was measured with a self-designed histomorphometry method using a millimeter grid in a stereomicroscope. The results demonstrated a significantly higher percentage of bone along the hydroxyapatite-coated implant than that seen with the titanium-surfaced implant types. PMID- 1299646 TI - Electron microscopy of bone response to titanium cylindrical screw-type endosseous dental implants. AB - This study investigated the undecalcified bone and enveloping tissues supporting commercially pure titanium one-stage and two-stage endosseous dental implants placed into the mandibles of adult mongrel dogs. Correlative light microscopy, transmission electron microscopy, and high-voltage transmission electron microscopy demonstrated a dynamic bone interface to the implants. Mineralized tissue was routinely observed within 20 to 50 nm from the implant interface, separated from the implant interface only by an electron-dense deposit. The densely mineralized collagen fiber matrix was oriented parallel to the implant interface, as were osteocytes that were found close to the interface. Osteocytic projections progressed through canaliculi, often directly to the implant interface. Unmineralized areas that appeared to have the potential for mineralization were also identified. PMID- 1299647 TI - Comparative implant research in dogs: prosthodontic protocol using two-stage ceramic endosseous dental implants. AB - This report describes one phase of a long-term comparative implant investigation involving 20 of 120 endosseous implants placed in 30 adult mongrel dogs. Fixed prostheses involving 16 of the 20 (4 control implants) two-stage ceramic endosseous implants have been provided using routine prosthodontic procedures and the limited prosthetic components available for the Bioceram Series II implant system. The prostheses have proven to be functional with minimal maintenance. To date, after 1 year of follow-up, 2 of the two-stage implants have exhibited problems caused by fracture of the hexagonal collar. None of the implants to date has been lost and none of the fixed prostheses has required re-cementation or any other type of maintenance other than normal hygiene. Clinical evaluation suggests continued implant and prosthesis serviceability after 1 year in function. PMID- 1299648 TI - A multicenter study of overdentures supported by Branemark implants. AB - Nine clinical centers participated in a prospective study of overdentures supported by Branemark implants in the maxilla or mandible. The study initially comprised 133 patients provided with 117 implants placed in the maxilla and 393 implants placed in the mandible. The preliminary results indicate a success rate in the mandible comparable with the reports on fixed prostheses. Conversely, overdenture treatment in the maxilla seems to be less favorable than previous reports of fixed restorations. The differences between the fixed and the present overdentures in the maxilla were mainly based on differences in patient selection and bone quality. A total of 32 implants was mobile and removed and another 29 implants were lost to follow-up because of patient dropout up to the first annual checkup after denture placement. A higher implant failure rate occurred in the maxilla. Mucosal reactions were also more unfavorable around implants placed in the maxilla. PMID- 1299649 TI - A retrospective study of osseointegrated skin-penetrating titanium fixtures used for retaining facial prostheses. AB - This investigation was conducted to evaluate osseointegrated skin-penetrating facial titanium implants used for anchoring facial prostheses over a 5-year period and to recommend guidelines for the use of osseointegrated implants in the restorative treatment of auricular and orbital defects. The total success rate for implant survival was 95.6% in the auricular defects and 67.2% in the orbital defects. Approximately 10% of the patients will have some skin problems, whereas the remaining 90% will have no or minimal problems. The possibility of achieving osseointegration around an orbital defect is not as good as in the mastoid process. Success criteria for the use of implants in the craniofacial region are given. PMID- 1299650 TI - Restoration of maxillary residual ridge atrophy using Le Fort I osteotomy with simultaneous endosseous implant placement: technical report. AB - When residual ridge atrophy of the edentulous mandible and maxilla is accompanied by a skeletal Class III jaw relationship, surgical correction is necessary for optimal functional, phonetic, and esthetic results whenever implant-supported prostheses are to be placed. A method is described in which a single procedure combines the endosseous placement of nonsubmerged titanium implants in appropriate prosthetically predetermined locations with defined advancement of the maxilla. Preoperative diagnostic examinations, cast simulation, and transfer of the latter to the site of surgery are of the utmost importance. PMID- 1299652 TI - Reparative bone growth in an extremely atrophied edentulous mandible stimulated by an osseointegrated implant-supported fixed prosthesis: a case report. AB - This case report demonstrates that severe disuse atrophy of an edentulous mandible can be changed to reparative bone growth through restoration of function and masticatory ability using an osseointegrated implant-supported fixed prosthesis. In 8 years, bone height in the retroforaminal area nearly doubled and a new bony layer remodeled the cranial roof of the mandibular canal. PMID- 1299651 TI - IMZ implants placed into extraction sockets in association with membrane therapy (Gengiflex) and porous hydroxyapatite: a case report. AB - A buccal plate destroyed by the inflammatory process as a result of a longitudinal root fracture was completely restored by the combined use of an IMZ implant placed in the alveolus of the fractured maxillary central incisor and the principles of guided tissue regeneration. A Gengiflex membrane was used to cover the implant, and porous hydroxyapatite was used as grafting material. At the 6 month reentry, the defect around the implant was completely filled by mineralized tissue. PMID- 1299653 TI - Toxicity of the staphylococcal protein A immunoadsorption column. PMID- 1299654 TI - Role of plasmapheresis in acute disseminated (postinfectious) encephalomyelitis. AB - Acute disseminated encephalomyelitis (ADEM) is a demyelinating central nervous system disease that is associated with high morbidity and mortality. Although the recognition of ADEM may be facilitated by newer imaging techniques, the optimal treatment of this disease remains uncertain. We describe 4 patients with severe ADEM who responded to treatment that included intensive plasmapheresis. Two of the patients were in coma at the time that plasmapheresis was instituted, and all 4 patients made an excellent recovery. Immunologic studies revealed increased serum IgA levels, increased circulating immune complex levels as measured by the Raji cell assay, and decreased numbers of T and B cells prior to treatment of ADEM. These abnormalities improved following plasma exchange. Plasmapheresis appears to be effective in reversing the neuropathologic process in ADEM. The role of this treatment modality in ADEM requires further evaluation in controlled clinical trials. PMID- 1299655 TI - Subacute (acute, persistent) thrombotic microangiopathy. AB - Six patients with prolonged acute courses of thrombotic microangiopathy are reviewed. These patients had in common courses of acute disease requiring plasma support for more than 3 months, with subsequent complete remission. Plasma support requirements may be prodigious, and the acute course may require more than 100 plasma exchanges before a stable remission is achieved. These patients appear to represent a subset of thrombotic microangiopathy distinct from the more common acute T.T.P. course, which resolves in 3-6 weeks, and the chronic relapsing pattern, which may have a short or prolonged acute course. PMID- 1299656 TI - Evaluation of elutriated single donor platelets collected and stored in a closed system. AB - Single donor platelets (SDPC) were collected by the elutriation technique in a closed-system integrated with large storage containers. Seven runs of SDPC were stored in a 1.5 liter polyvinyl-chloride trimellitate (PVC-TOTM) storage container, making the ratio of platelet concentrate volume to container volume 1:4.5. An equal volume of pooled multiple donor platelet concentrates (MDPC) was stored in parallel under the same conditions. All haematological data were comparable for both products, except for the degree of leukocyte contamination (5 fold increase in the pool). Under these conditions, the functional, morphological, and metabolic characteristics of elutriated platelets throughout 7 day storage were superior to those of pooled platelets. Although the platelet count was not significantly different in both types of concentrates, the mean pH of pooled MDPC fell to 6.0 on day 5 of storage. Leukocytes were shown to contribute to this pH fall. The extent of cell damage, however, as evidenced by LDH leakage (42.7 LDH units/10(11) platelets/day by differential centrifugation, compared to 5.3 units by elutriation) could not be explained solely on the basis of the leukocyte effect. This indicated that the processing method itself influences the platelet quality. By increasing the surface/volume ratio of SDPC, the initial pH of 7.1 was well maintained throughout storage, platelet metabolic rate was slowed, and the function and ultrastructure improved significantly. PMID- 1299657 TI - Therapeutic cytoreduction in a 7-month-old baby with acute leukemia. AB - A 7-month-old girl with acute biphenotypic leukemia [t(4;11)] had accompanying anemia, thrombocytopenia, and a white blood cell count of 535,000/microL with 98% blasts. Before instituting chemotherapy, therapeutic leukapheresis was done to reduce the threat of complications from leukostasis. Using a Cobe Spectra blood cell separator primed with modified blood, we processed 1,395 mL of her blood, removing 201 mL of the buffy coat containing 5.8 x 10(10) white blood cells. This reduced the WBC count to 301,000/microL. Only a single procedure was done, without significant complications. The rationale of this preparatory cytoreduction is discussed critically. Subsequent chemotherapy resulted in a long lasting remission. PMID- 1299658 TI - Selective removal of cholesterol by plasmapheresis and the progression of atherosclerosis. AB - There is a strong correlation of plasma cholesterol levels with the risk of coronary heart diseases as shown by epidemiologic studies. This study was undertaken to evaluate the effect of plasma cholesterol lowering on the progression of atherosclerosis in the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit. The effect of cholesterol lowering, which was accomplished by thermofiltration (on-line plasma separation with plasma filtration at 39 degrees C) was evaluated by comparison between treated and untreated control groups. Thermofiltration reduced significantly the mean plasma level of total cholesterol (284 vs. 655 mg/dl, P = 0.0005) and the percent aortic area occupied by atherosclerotic plaque (15.0 vs. 44.2%, P = 0.0003). The total lipid and cholesterol contents in the aortas in the treated group were also significantly lower than those in the control group. Microscopically, thickness measurements of the lesions showed that the mean thickness of the fibrous cap and the ratio of the thickness of the intima to that of the media were smaller for the treated group than the control group. This study demonstrated the slowing or stopping of the progression of atherosclerosis by lowering the plasma total cholesterol level in WHHL rabbits. PMID- 1299659 TI - Collection of peripheral blood mononuclear cells as a byproduct of plateletpheresis with two different blood cell separators. AB - Peripheral blood mononuclear cells (PBMC) were collected as a byproduct of plateletpheresis of normal blood cell donors using modifications to standard automated protocols on either the CS-3000 or Spectra blood cell separator machine. Comparison of the PBMC products obtained showed X +/- SD WBC yields of 5.3 +/- 3.4 vs. 3.8 +/- 2.0 x 10(9) with the CS-3000 and Spectra, respectively (P < .0001). The majority of the cells were lymphocytes, with 13-15% monocytes with both machines. Sixteen percent of the WBC collected with the Spectra, but only 1% of those collected with the CS-3000, were granulocytes. The CS-3000 PBMC product contained fewer RBC (0.2 +/- 0.1 x 10(11) vs. 2.4 +/- 0.6 x 10(11)) and more platelets (1.6 +/- 0.6 x 10(11) vs. 0.35 +/- 0.39 x 10(11)) in a smaller volume (40 +/- 14 ml vs. 229 +/- 37 ml) than the Spectra products. Comparison of the platelet collections harvested when PBMC were also collected to platelets harvested using standard procedures on the same machine showed no change in platelet, WBC, or RBC yields for the Spectra. A significant increase in mean WBC contamination from 40 +/- 56 x 10(7) to 112 +/- 205 x 10(7) and a small, but statistically insignificant, decrease in platelet yield from 4.1 +/- 1.2 x 10(11) to 3.9 +/- 1.8 x 10(11) was observed in the CS-3000 platelet collections when PBMC were harvested. There was no sustained change in donor lymphocyte counts and no change in acute donor side effects or time requirements when PBMC were collected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299660 TI - Folinic acid does not mobilize hemopoietic progenitors following repeated consolidation chemotherapy for acute leukemia. AB - Folinic acid (FA) has been reported to expand the pool of peripheral blood stem cells (PBSC) after chemotherapy. We evaluated the efficacy of FA for harvesting PBSC following cytotoxic chemotherapy in 4 patients with acute leukemia. After achieving a complete remission (CR), 3 courses of chemotherapy for a consolidation of the CR were administered to the patients. Two successive cycles of leukapheresis were performed during the recovery phase from consolidation chemotherapy, which consisted of an intermediate dose of cytosine arabinoside. For the second cycle of leukapheresis, FA was administered intravenously at a dose of 50 mg/day following consolidation. The yields of either mononuclear cells or burst-forming units-erythroid (BFU-E) were not affected by FA administration. In contrast, the yields of colony-forming units-granulocyte/macrophage (CFU-GM) were significantly decreased in all patients compared to the CFU-GM yields after the first cycle of leukapheresis (P = 0.032). Thus FA is considered not to be effective in expanding the peripheral blood progenitor pool when given in a fashion different from the original report. PMID- 1299661 TI - Use of the Fenwal small volume collection chamber for granulocyte collection on a 22 kilogram donor. PMID- 1299662 TI - Hemostasis abnormalities associated with prosthetic devices and organ transplantation. PMID- 1299663 TI - Long-term response to sequential hemibody radiotherapy in Waldenstrom's macroglobulinemia. PMID- 1299664 TI - [Conversion laparatomies during cholecystectomies under laparoscopy. Apropos of 285 consecutive cholecystectomies]. AB - Retrospective analysis of a consecutive series of 285 cholecystectomies carried out by laparoscopy showed that 47 patients (17.5%) required conversion laparotomy. In 55% of these cases the conversion was due to difficulty in dissecting the gallbladder or cystic duct. Peri-operative cholangiography should be performed routinely, not only to verify the vacuity of the common bile duct (13% of the conversions) but, more particularly, to ensure the integrity of the principal biliary pathway during the dissection (8.5% of the conversions). Cholecystectomy under celioscopy is a proven and safe technique, on the condition that all stages of classical surgery can be carried out under good conditions. PMID- 1299665 TI - [Aimed fistulization in spontaneous ruptures of the thoracic esophagus after delayed diagnosis. Apropos of 4 cases]. AB - Of four cases of spontaneous rupture of thoracic esophagus treated, three were the object of direct fistulization on a Kehr's drain because of the delay in diagnosis. This technique remains valid since it provides satisfactory drainage without excluding the focus, reduces the time of hospital care when compared with that for simple suturing, and appears preferable to methods of esophageal exclusion which often require a secondary surgical procedure. PMID- 1299666 TI - [Restoration of colonic continuity after Hartmann's operation]. AB - A retrospective analysis of data from 69 patients treated by Hartmann's operation between 1981 and 1991 determined prognostic factors for colon continuity re establishment and the mortality of this second intervention. The 15 patients who died during the first month after the Hartmann's operation were excluded from the study, the 54 survivors including 32 men and 22 women, mean age 68 +/- 12 years (range 19 to 87 years). The initial indication for surgery was: complicated sigmoid diverticulis (n = 26), cancer of colon (n = 14) or other site (n = 14). Colon continuity was re-established in 23 patients (42.6%), including 15 men and 8 women, mean age 60 +/- 10 years (range 38 to 78 years). In this latter group, 82.6% of the patients were under 70 years of age, indicative of a significant effect of age (p < 0.001) on re-establishment of continuity. Secondary anastomosis was obtained in 65.4% of cases of complicated sigmoid diverticulitis, whereas re-establishment of continuity was possible in only 7.1% of colon cancer patients (p < 0.001). The mean duration prior to re-establishment was 4.8 +/- 1.6 months (range 2.5 to 9 months). Morbidity was high (47.8%) and mortality 4.3% (1 patient). Hartmann's operation remains indicated for stages III and IV of complicated sigmoid diverticulosis, as well as for other benign affections (volvulus of sigmoid, perforation of sigmoid following injury), although it must be recognized that the possibilities of re-establishment are limited more in elderly patients and that fewer patients with colon cancer can benefit from the procedure. A period of 3 to 4 months appears sufficient to allow healing of the inflammatory phenomena of the initial operation, without the development of excessive retraction of the rectal stump. PMID- 1299667 TI - [Volvulus of the colon. Apropos of 37 cases]. AB - A retrospective study of 37 case reports of patients with volvulus of the colon was carried out to define diagnostic and therapeutic strategies. The group comprised 22 men and 15 women, mean age 69 +/- 4 years (range 26-88 years), the volvulus being located in the sigmoid colon (n = 23), ascending colon (n = 13) or transverse colon (n = 1). The diagnosis, suggested by the straight abdominal film in almost all cases, was confirmed by a barium enema in 70% of cases. Treatment was surgical in 30 patients (81%) including 12 as emergency operations. Mortality was 5.4% (2 cases), and morbidity high (43% including fatal complications) the majority of adverse reactions being respiratory. Volvulus of the ascending colon was treated by hemicolectomy in 9 cases with no mortality or relapse. In patients with sigmoid volvulus, a "medical" reduction was performed in 7 patients, with success in 5 cases, one recurrence and no mortality, ideal sigmoidectomies in 14 cases resulting in one recurrence and no mortality. Right hemicolectomy appears to be the technique of choice even for urgent cases, there being no contraindications to a one-stage re-establishment of continuity. Inversely, an urgent intervention should at all costs be avoided in cases of sigmoid volvulus, a "medical" reduction (radiology, intubation, endoscopy) allowing preparation of the patient for a deferred ideal sigmoidectomy. Obviously, failure to reduce the volvulus or signs of colon necrosis require urgent surgery and raise the problem of whether or not to re-establish colon continuity. PMID- 1299668 TI - [Peritoneal dialysis catheters. Immediate outcome after 30 days]. AB - Results of a retrospective study of 124 peritoneal dialysis catheters introduced in 74 patients from October 1982 to November 1991 showed that 91% of catheters were functional at 30 day follow up, allowing continuous ambulatory peritoneal dialysis to proceed under satisfactory conditions. However, surgical replacement was necessary in 21.81% (26 catheters) during the first month, due essentially to mechanical complications: exteriorized or non exteriorized leaks (7 cases), dysfunction with faulty perfusion or emptying (11 cases) and catheter displacement (3 cases). Five catheters (4.25%) had to be withdrawn because of infection, suggestive of the need for prophylactic antibiotic therapy. No determining factor could be found in the present series or in the literature to explain the genesis of these mechanical complications, the cause of which is without doubt multifactorial. Rapid surgical replacement allows functional survival of the majority of catheters without increasing the risk of infection. PMID- 1299669 TI - [Acute chyloperitoneum]. AB - A patient presenting with the symptomatology of an appendicular syndrome was later diagnosed as having an acute chylous ascites. The etiology was an acute edematous pancreatitis, the anatomy of the lymphatic pathways with the proximity of the pancreas explaining this etiology, as well as the possibility of a pancreatitis secondary to obstruction of the thoracic duct. The early post operative clinical course was marked by an acute occlusion of small intestine on the 15th day, related to the adherence potency of the chyle. A general review of the acute chylous ascites syndrome showed the prognosis to be generally favorable, with a mortality of 4%, in contrast to the 40% mortality reported for the chronic chylous ascites of adults. PMID- 1299670 TI - [Perineal hernia after abdominoperineal amputation. Role of epiploplasty and/or irradiation]. AB - Healing of the perineal wound after abdominoperineal amputation is a difficult technical problem for surgeons to resolve. The majority of current therapeutic protocols include pre- or post-operative radiotherapy, and most study results show a reduction in perineal relapses when compared with a control group, but at the price of delayed healing of the perineal wound. This delayed healing reaction varies with the radiation dose. The use of epiploplasty shortens the healing period, but when performed after pre-operative radiotherapy it can predispose to the development of a perineal hernia. Four cases of this complication are described. No standard procedure for treatment of these hernias exists, and although it is possible to use the uterus to fill the perineal cavity, the most effective method appears to be a double perineal and abdominal pathway using a plate. PMID- 1299671 TI - [Splenic pregnancy. Apropos of a case]. AB - Still nowadays the extrauterine pregnancy causes the 10% of maternal deaths, also in the most developed countries. The splenic localization is really exceptional. The authors of this article describe a case they have studied, by drawing the attention on the criteria followed in order to obtain an early and correct diagnosis for a reduced mortality rate. PMID- 1299673 TI - [Apropos of a large right diaphragmatic hernia]. PMID- 1299672 TI - [Acute biliary and alcoholic pancreatitis: two different diseases?]. AB - An analysis of 174 patients with an acute biliary or alcoholic pancreatitis who were admitted to the Surgical University Clinic Mannheim from 1986 until 1989 showed significant differences in the course of the disease and surgical treatment. 77.2% of our patients with an acute alcoholic pancreatitis were men. Mean age of all patients was 45.7 years. 72.3% of our patients had a mild pancreatitis and 27.7% a necrotising pancreatitis. In 26.8% of the patients an operation was necessary (necrosectomy, lavage of the lesser sac). In 35% of these patients occurred complications. Total lethality was 9.9% (mild pancreatitis: 0%, severe pancreatitis: 17.6% and total necrosis of the pancreas: 63.6%). 58.9% of our patients with an acute biliary pancreatitis were women. Mean age of all patients was 62.4 years. In 50% of all cases an operation was necessary (in most cases cholecystectomy and extraction of a prepapillary concrement but also necrosectomy and lavage of the lesser sac). In 17% of these patients occurred complications. Total lethality was 11.0% (mild pancreatitis: 0%, severe pancreatitis 8.3% and total necrosis: 77.7%). The conclusion is a surgical therapy depending of the cause of the pancreatitis and also a different prognosis of the disease. PMID- 1299674 TI - [Muciparous cystadenoma of the ovary, fulminating course: apropos of a case]. PMID- 1299675 TI - [Gastric necrosis after endoscopic sclerosis of a hemorrhagic ulcer. Apropos of a case]. PMID- 1299676 TI - [Measuring visual field loss by automated perimetry in chronic glaucoma stabilized by trabeculectomy]. AB - The progression of field loss was determined by Humphrey Automated threshold perimetry in the short and intermediate term after surgical trabeculectomy for chronic glaucoma: mean indices (MD, PSD et FOV) were studied before and after normalisation of the intraocular pressure. Risk factors such as secondary glaucoma, previous visual field defects and cardiovascular risk factors were significantly correlated to poor or bad progression of field loss: the mean variation of MD = +1.23 dB +/- 2.84 (p < 1.5%), the mean variation of PSD = 0.50 dB +/- 1.37 (p < 6%), but the mean variation of FOV was not significant; so 36% of field defects were improved, 42% were stabilized and 22% were aggravated. When the risk factors were absent, 86% of field losses were stabilised but when cardiovascular factors were present, only 64% were stabilised. These risk factors can also be used to ascertain the prognosis of post-surgical progression of visual field, as already shown in previous reports. Automated threshold perimetry was useful to study the visual field progression with standardized and reliable numerical parameters, allowing statistical computerised management of the patients with glaucoma. PMID- 1299677 TI - [Surgery of idiopathic epimacular membranes. Prognostic factors]. AB - Seventy consecutive cases of idiopathic epimacular membrane removal were reviewed in order to evaluate the prognosis factors of this surgery. The characteristics analyzed where the duration of the symptoms, pre and postoperative visual acuity and the macular changes on fluorescein angiography. The mean follow-up after surgery was 9 months. Mean preoperative visual acuity was 0.17 and the mean best postoperative visual acuity 0.43. Visual acuity improved by 2 lines or more in 81% of the cases and the mean improvement was 3.5 lines. The complications of epimacular membrane surgery included nuclear cataract (10 eyes underwent cataract surgery), peripheral retinal breaks (3%), and retinal detachment (3%) successfully operated. Three of the main preoperative data were related to better postoperative visual outcome: preoperative visual acuity: eyes with visual acuity of 0.16 or more tended to have better postoperative vision than eyes with poorer preoperative vision (mean postoperative visual acuity 0.5 and 0.34 respectively; p < or = 0.05); duration of visual impairment before surgery: eyes with a visual impairment of less than 2 years had better postoperative vision than the others (mean postoperative visual acuity, 0.5 and 0.3 respectively; p < or = 0.05); the absence of preoperative angiographic macular edema: eyes without preoperative macular edema had better postoperative vision than the others (mean postoperative visual acuity: 0.5 and 0.4 respectively; p < or = 0.05). The normal postoperative pattern of macular vessels and foveolar shape was also a statistically significant factor of good vision recovery. PMID- 1299678 TI - [Bacterial endophthalmitis. Ophthalmological results of a national multicenter prospective survey]. AB - Under the aegis of the GEEP (Groupement d'Etudes Epidemiologiques et Prophylactiques) a prospective multicentre study concerning bacterial endophthalmitis was carried out over a period of one year long with the contribution of 64 metropolitan ophthalmologic hospital departments. During this survey 143 cases of post surgical endophthalmitis were recorded: 111 of them were secondary to elective surgery, 32 developed after a perforating eye injury. Twenty-four cases of endophthalmitis developed in the absence of surgery were therefore called "medical" endophthalmitis. The frequency of endophthalmitis after elective surgery was 0.32%, and 2.8% after penetrating eye injury. Intraocular samples were obtained in 61.5% of the cases of post surgical endophthalmitis. 53 bacteria were isolated from 50 cases of endophthalmitis. The bacterial nature of the endophthalmitis was proved in 35% of these cases of post surgical endophthalmitis. Bacteria isolated from these cases of post surgical endophthalmitis were gram positive in 86.7%, and gram negative in 13.3% of cases. 20 bacteria were isolated from pseudophakic eyes: 10 of them were Staphylococcus epidermidis. The visual prognosis of endophthalmitis depends on the strain: visual acuity was more than 1/10 in 68% of cases of Staphylococcus endophthalmitis infection, but in only in 7% of cases of Streptococcus endophthalmitis infection. Intraocular injections of antibiotics both in the anterior chamber and in the vitreous, and vitrectomy increased the quality of the visual result. Three months after post surgical endophthalmitis, 35% of those eyes who received systemic and periocular antibiotic therapy, combined with intraocular antibiotics, with or without vitrectomy, recovered a visual acuity of 4/10 or more, instead of only 18% in the group without any intraocular therapy. PMID- 1299679 TI - [Conjunctival myiasis, a frequent pathology in Corsica]. AB - Fifteen cases have been reported and treated in the Ajaccio eye department. The larva involved is most of the time Oestrus ovis and is responsible for an acute unilateral conjunctivitis. The conjunctiva is swollen and scattered with petechiae due to the hooks of the larva. Five to 15 maggots are extracted with a forceps after instillation of topical anesthetic, leading to relief of symptoms within a few days. PMID- 1299680 TI - [Multifocal choroiditis]. PMID- 1299681 TI - [Recurrent pseudo-conjunctivitis in an infant. Diagnosis and treatment]. PMID- 1299682 TI - [Keratoplasty and explantation of the anterior chamber followed by implantation sutured to the sclera]. PMID- 1299683 TI - Comparing health care systems: what nations can learn from one another. PMID- 1299684 TI - The United States: breakthroughs and waste. AB - The health system of the United States is in a paradoxical position. At its best, the system is a magnet for those seeking the latest technical breakthroughs. It can offer that excellence because there have never been effective financial constraints on the imagination; the system has become a major economic frontier, at which professional and other entrepreneurs successfully seek their fortune. At the same time, the system is leaving increasing numbers of Americans frustrated and disillusioned. It is beset by excess capacity in many areas, is needlessly expensive, and often bestows unnecessary health services. Yet only the experts are aware of these flaws; most Americans still express high satisfaction with the quality of the services they receive from their doctors and hospitals. The public's major misgivings arise over the awkward and inequitable way in which American health care is financed. The typical private health insurance policy, for example, is tied to a particular job. If the job is lost, so is the health insurance. Furthermore, these policies are priced on actuarially "fair" principles, so sick individuals are forced to pay higher insurance premiums than relatively healthy ones and chronically ill persons often cannot obtain health insurance coverage at any price. Although there are public programs to catch many persons not privately insured, the coverage tends to be insufficiently extensive and deep. Some 35 million Americans, mostly poor, have no health insurance whatsoever. Unfortunately, at this time there is no political force in the United States strong enough to reform the American health system toward greater social equity and economic efficiency, whereas there are numerous groups powerful enough to block whatever reform might harm their own narrow economic interests. Other nations can learn from America's clinical and organizational innovations in health care delivery. They can also learn what not to do by studying the unseemly way in which American health care is financed. PMID- 1299685 TI - The United Kingdom: effective, efficient, equitable? AB - The British National Health Service (NHS) has, since its inception, aimed to make health care available to all regardless of income, and it has managed to achieve this goal while keeping costs lower as a proportion of the gross domestic product than many Western countries and at the same time assuring equitable distribution of resources regionally. Until the reforms introduced by the 1989 White Paper, the NHS was characterized by centralized financing and regulation; despite some problems in the delivery and management of care, the system was a popular one. The new reforms hope to enhance efficiency in the NHS by stimulating competition and further decentralizing the management of health care. However, it is not at all certain that in practice the reforms will have the desired effect. Initial costs will be high, people may not respond to incentives as predicted, and the quality of care and access to it could well deteriorate. Nations planning to use the U.K. system as a model are advised to use caution. PMID- 1299686 TI - Japan: maintaining equity through regulated fees. AB - Japan was the first non-Western country to introduce social insurance and the first to achieve universal coverage. It has been very successful in helping to bring about high health levels among its citizens at reasonable cost. Consequently, it provides a unique model for the newly industrialized countries of how to adapt modern technologies in structuring their own health care systems. Japan's financing system is organized by the government. Coverage is mandated for all citizens and is supplied by a number of insurance plans, whose variety reflects the differences in their development. The country relies mainly on the private provision of health care, delivered from physician-owned clinics and hospitals. The most prestigious facilities, however, are the public hospitals. Services are fragmented between clinics and hospitals, which compete for a share of the patients in their area. Patients can choose where to seek medical services. Providers are paid by a nationally uniform method and rate, which are decided by one central agency. Increases in payment rates are tied to the ceiling set by the government's general expenditure limitations. A uniform fee schedule has helped to control costs and to ensure equitable access. Challenges remaining for Japan's health care system are caring for an increasingly elderly population and ensuring quality of care. PMID- 1299687 TI - Germany: solidarity at a price. AB - The health care system of the Federal Republic of Germany relies on the private sector for the financing, delivery, and payment of care. However, the private sector is regulated by the government to ensure that broad societal interests are being fulfilled. The system has managed to achieve comprehensive coverage and equal access for all citizens, freedom of choice for patients, high-quality medical care, and cost containment. The reason for this success is a combination of decentralized power and decision making and the establishment of an effective negotiation system that takes place at federal, state, and local levels. The system suffers from some problems, however, which will have to be addressed: the present structuring of hospital and ambulatory care results in excessively long lengths of stay in hospital; drugs are overprescribed; the supply of health professionals does not meet the country's needs; more nursing homes are needed; and eastern Germany must be fully integrated into the system. PMID- 1299688 TI - Canada: the real issues. AB - Canadians are, by and large, satisfied with their health care system. It is for them a symbol of their community and distinguishes them from the United States. Unlike the health system of that country, it is universal, comprehensive, and accessible, and it costs less as a percentage of GNP to run. The difference between the two systems is rooted in differences in funding. By providing coverage of medically necessary care under a single nonprofit payer (the provincial governments, with guidance and some funds from the federal government), the Canadian system avoids the large overheads and profit incentives that make a fragmented private insurance industry so expensive and inequitable. Whereas health insurance in Canada is socialized, care is not: patients are free to choose among providers, physicians are primarily in private practice, and hospitals are independent, nonprofit institutions overseen by boards of trustees. Canada and the United States view the challenges confronting the Canadian system differently. To Canadians, the real issue is how to improve the management of a popular, effective, and heretofore affordable system, so as to preserve it in a more hostile economic environment. The specific areas of concern are common to all health care systems in the developed world but bear little resemblance to the misleading images of Canada fabricated in the United States for internal political purposes. For Canadians, the proof of their system is that it works, while millions in the United States go without. PMID- 1299689 TI - On being old and sick: the burden of health care for the elderly in Canada and the United States. AB - The debate over health care reform in the United States has drawn Canada under the microscope. Canada's health care system is frequently offered as a model for American national health insurance. Curiously absent from this policy discussion is any talk about the relative out-of-pocket costs of alternative models. In this paper, we provide data on these costs for American and Canadian elderly for medical, hospital, and ambulatory pharmaceutical use. Despite the fact that the elderly in America are generally viewed as facing fewer problems with access and out-of-pocket costs than younger Americans, their direct costs far exceed those of their Canadian counterparts. We also present data suggesting that, despite these greater costs, rates of growth in use of these services by American elderly have followed roughly the same pattern as those found in Canada. If Uncle Sam retired north of the border, being old and sick would also mean being wealthier and happier. PMID- 1299690 TI - Private outlets for public limitations: the rise of commercial health insurance in Israel. AB - In recent years, dissatisfaction with aspects of the Israeli health care system has grown. Labor conflict and unrest, long waits for elective surgery, increases in out-of-pocket payments for health care, and declining government investment have given rise to a new phenomenon: the increasing use of private services. This has led consumers to seek financing sources for their private care and created opportunities for commercial insurers and sick funds to offer new insurance packages to meet this demand. As a result, over the last five years more than twenty commercial health policies and four mandatory supplemental policies provided by the sick funds are currently on the market. The market for these policies is small but growing, with consequences for the cost and quality of care, access, the level and composition of national expenditures, and the allocation of resources to both the public and private health systems. As the balance between private and public financing changes, so too do the trade-offs between differing objectives. Greater private pluralism and competition at the financing level have many advantages but also make it more difficult for government to manage the tradeoffs that occur. Thus, a changed emphasis in government regulation and policy-making is required. PMID- 1299691 TI - Health policy regimes and the single European market. AB - I examine the potential effects of the creation of a single European market on the health policy regimes of the twelve member states of the European Community (EC), arguing that few changes can be expected in the basic nature of those regimes and that a Community-wide health policy regime is unlikely to emerge in the near future. Domestic health policy regimes and care systems will remain the dominant approach to health care delivery, and it is not likely that the American approach will be adopted. However, EC legislation designed to create favorable trade, economic, and fiscal conditions may affect key industries like pharmaceuticals and health insurance, with consequences for national health policy regimes. Patterns in Community-wide policy-making suggest that it will become increasingly difficult to define health issues in purely domestic or international terms. PMID- 1299692 TI - Pharmaceutical regulation in the European Community: barriers to single market integration. AB - The European Community (EC) plans to create a single market for pharmaceutical medicines, but the drug industry is closely linked to cultural and societal values concerning health; to the national regulatory agencies responsible for the evaluation of safety, quality, and efficacy of new drugs; to multinational and domestic companies competing in national and international markets; and to varied interest groups of professionals and consumers organized along national and multinational lines. We review the history of the EC's policy proposals, examine reactions from all these interested parties, and assess the prospects for integration into a single market. The contentious debate that continues among the parties over national prerogatives, industrial interests, professional mandates, and consumer concerns clouds the prospects for a system of centralized drug registration that will be acceptable to all EC member states. PMID- 1299693 TI - Challenges in the provision of care for the chronically ill. PMID- 1299694 TI - Home care in old age: a lost cause? AB - I consider policy trends and the provision of home care for frail elderly people in four countries: Denmark, the United Kingdom, Germany, and the United States. The differing natures of the health and social services systems of each country and the welfare ideologies that underlie them have affected the expansion of home care for this group of people. Hence, Denmark--and to a lesser extent Britain- has relatively well developed networks of home care services, in contrast to Germany and the United States. However, any significant shift away from predominantly medical and institutional care to more home-based, social care is highly unlikely. PMID- 1299695 TI - Falling through the cracks: care of the chronically mentally ill in the United States, Germany, and the United Kingdom. AB - In comparing the development and strength of community-based services for the chronically mentally ill in the United States, Germany, and the United Kingdom, I analyze how the structure of each country's general medical system has influenced services for the chronically mentally ill and the extent to which more universal medical care systems are associated with stronger community-based systems for the mentally ill. Community-based services are frail and inadequate in all three countries, in each country for different reasons. The specifics of organization of the health care system seem less important in shaping these outcomes than the status of mental health care as a national priority. PMID- 1299697 TI - The emergence of gay and lesbian studies. PMID- 1299696 TI - Residential care for the elderly. AB - This article maps variations in a standardized way in residential care for elderly people in three Western nations. Measured by the number of available places per person aged sixty-five and over and by the number of staff members per bed in nursing homes, the United Kingdom has the most highly developed standards. The United States ranks second, with Germany lagging considerably behind. The variations are explained by four variables: the pressure of the problem, as defined by the percentage of the population aged sixty-five and over; the caretaker potential in the family system, which alleviates this pressure; the structure and financing of the supply of residential care; and decision-making procedures in health care policy-making. My analysis emphasizes the last two variables. In the United Kingdom and the United States, the public and private providers who supply care have either political or market incentives to expand their services. Germany's mix of public and private, by contrast, is dominated by voluntary associations that are neither responsible to an electorate nor allowed to make profits. Thus, their clients do not have opportunities to articulate their needs. Health care decision making in Germany takes place through a collective bargaining process between the sickness funds and the providers. In such a system, the interests of groups who are not represented at the negotiation table--such as the elderly--tend to be neglected. A national health system of the British type links political decision makers via the election mechanism more closely to the concerns of the public. As older people represent growing proportions of the electorate, their needs find more adequate consideration in the policy process. In the United States, political officeholders also have to pay attention to the needs of increasingly organized older people, since the tax financed and federally regulated Medicaid system is largely responsible for financing long-term care for the elderly. PMID- 1299698 TI - Matters of fact: establishing a gay and lesbian studies department. AB - This article describes the establishment and operation of the first Gay and Lesbian Studies Department in the United States. The evolution of instructional services, administrative and student services, and various aspects of institutionalization are discussed. Short statements by two faculty members of the new Department follow the main article. PMID- 1299699 TI - Gay and lesbian studies in The Netherlands. AB - Gay and Lesbian Studies have been rather successful on an institutional level at Dutch universities. The article discusses the social and scholarly backgrounds of this development, the work being done, and the social reception of gay and lesbian studies. The deployment of gay and lesbian studies was possible thanks to the democratic structure of Dutch universities, and to a general acceptance of the aims of gay and lesbian emancipation in Dutch society. The article delineates also the limitations of the Dutch situation, in terms of the "cordon sanitaire" or minority perspective in which gays and lesbians seem to become enclosed. Also, the future perspectives of gay and lesbian studies are discussed. PMID- 1299700 TI - Lesbian studies emerging in Canada. AB - This paper provides an overview of Lesbian Studies in Canada historically and currently. The methodology integrates the factual with personal accounts and perceptions. The first sections touch upon theoretical aspects, including: what is Lesbian Studies, the pros and cons of merging Lesbian and Gay, or Lesbian and Women's Studies, mainstreaming versus creating a separate discipline and the threat of cooptation. A brief historical account traces evidence of Lesbian Studies in antiquity, and in the United States and Europe in recent decades. Reports from various Canadian institutions discuss the extent or lack of Lesbian Studies to date. A section on francophone institutions outlines the grass-roots cultural and political pinnings which are necessary to making Lesbian Studies possible in the academy. The paper then focuses on the Lesbian Studies Coalition of Concordia (Montreal), a student group which has struggled for the first series of Lesbian Studies credit courses in Canada. PMID- 1299702 TI - Homosexual, gay, and lesbian: defining the words and sampling the populations. AB - The lack of both specificity and consensus about definitions for homosexual, homosexuality, gay, and lesbian are first shown to confound comparative research and cumulative understanding because criteria for inclusion within the subject populations are often not consistent. The Description section examines sociolinguistic variables which determine patterns of preferred choice of terminology, and considers how these might impact gay and lesbian studies. Attitudes and style are found to influence word choice. These results are used in the second section to devise recommended definitional limits which would satisfy both communication needs and methodological purposes, especially those of sampling. PMID- 1299701 TI - History's future: reflections on lesbian and gay history in the community. AB - From its beginnings in the nineteenth century, the lesbian and gay political movement has been linked to a search for lesbian and gay history. In the post Stonewall period, community-based historians have been fostering interest in the lesbian and gay past and developing distinctive forms for disseminating their research--in particular, the lesbian/gay archive, the slide-lecture presentation, and the community-based audience. Analyzing the content of these forms reveals how the fascination of the artifact, the image, and the Other fosters the construction of both knowledge and identity. It is these forms of knowledge, rather than their content as such, that are in danger of being forgotten as lesbian and gay studies becomes academically institutionalized. PMID- 1299703 TI - Deconstruction, lesbian and gay studies, and interdisciplinary work: theoretical, political, and institutional strategies. AB - The problematic of cultural self-representation is examined in light of the development of lesbian and gay studies. The issues are examined through the lens of deconstruction as theoretical and political strategy. This examination suggests the value of interventionist work, and seeks to articulate an understanding of interdisciplinary work as exemplary of such an interventionist practice and politic. Relevant theoretical and political implications are explored, most especially in terms of the future developments of lesbian and gay studies. PMID- 1299704 TI - The mark of sexual preference in the interpretation of texts: preface to a homosexual reading. AB - Since reading is an interaction or confrontation between the reader and the text- an interaction that depends upon the background and perspectives of the reader as well as on the text being read--we can assume that the dynamics of sexuality and sexual object choice will influence how readers ascribe meaning to literary texts. In fact, although other aspects of our identities come into play when we read, sexual identity is unique and central because of the role that it plays in the creation of subjectivity. Specifically, male homosexuality informs and structures the reading of texts. But what does it mean to be a homosexual reader or to effectuate a homosexual reading of a particular text? PMID- 1299705 TI - Generations and paradigms: mainstreams in lesbian and gay studies. AB - The development of lesbian and gay studies is traced from the Stonewell period of the late sixties and early seventies to the present. The effort to establish lesbian and gay studies has brought together several generations of scholars who have produced a variety of conceptual worldviews. These generational mainstreams of thought in lesbian and gay studies include the search for authenticity (1969 1976), the social construction of identity (1976-present), essential identity (1975-present), difference and race (1979-present), and cultural studies (1985 present). PMID- 1299706 TI - Teaching homosexual literature as a "subversive" act. AB - If taught in a way that exposes students extensively and closely to its texts, homosexual literature can "subvert" the long-standing cultural notion that homosexuality is and should remain "unspeakable" and "untouchable." The author's working methods and materials in his gay and lesbian literature courses at the New School for Social Research, where he has been teaching the subject since 1979, are organized according to those principles. His courses also have a secondary "subversiveness" in the present academic climate, in implicitly dissenting from the dominant "new-inventionist" trend in gay studies now. PMID- 1299707 TI - Relapses in multibacillary leprosy patients after stopping treatment with rifampin-containing combined regimens. Marchoux Chemotherapy Study Group. AB - During the decade between the mid 1970s and the mid-1980s, 12 rifampin (RMP) containing combined regimens were tested among lepromatous leprosy patients in the Institut Marchoux. The 384 patients who were seen at least once during the period beginning 12 months after completion of treatment were considered eligible for analysis of the relapse rate. By the end of May 1991, relapse, manifested by a significant increase of the bacterial index (BI) and the appearance of new lesions with a BI greater than that of preexisting lesions, had been observed in 68 (17.7%) of these patients. Relapse was confirmed by the presence of viable Mycobacterium leprae in skin biopsy specimens obtained from 54 of the first 61 cases; virtually all of the isolated strains remained susceptible to RMP. The relapses occurred late, about 5 +/- 2 years after stopping treatment; the shorter the duration of RMP administration, the earlier the appearance of the relapse. The variations of the relapse rate among regimens were considerable: total relapse rate ranged from 2.9% to 27.8%, and the relapse rate per 100 patient years of observation ranged from 0.8 to 6.9. Among the 12 regimens, only the WHO/MDT yielded an acceptable relapse rate (defined as a rate lower than 1.0 per 100 patient-years). However, because the mean duration of follow up was shortest among the patients treated with WHO/MDT, the relative low relapse rate among these patients must be interpreted with great caution. PMID- 1299708 TI - Does isoniazid increase the hepatotoxicity of the combination prothionamide dapsone? Isoprodian Study Group. AB - In order to assess the potential additive liver toxicity of isoniazid to that of a thioamide-containing treatment, a prospective, randomized, double-blind trial of 24 weeks' duration involving 772 adult patients was conducted in four leprosy centers--two in India, one in Madagascar, and one in the Ivory Coast. Patients with multibacillary leprosy were given daily 100 mg dapsone (DDS) and 350 mg prothionamide (PTH) plus monthly 600 mg rifampin (RMP) in combination either with 350 mg isoniazid (INH) or with a placebo. After clinical and laboratory (including HBs-Ag testing) examinations on admission, the side effects (especially gastrointestinal disturbances and liver toxicity) were assessed at regular intervals during treatment by laboratory testing (aminotransferases, bilirubin, alkaline phosphatase) and by recording spontaneous complaints. Analysis of the frequency and seriousness of the side effects was made before breaking the code (with or without INH). Although 10% of the patients had liver toxicity leading to stopping treatment, no significant difference in the occurrence of side effects was observed between patients treated with or without INH. Most (75%) of the observed side effects occurred during the first 4 weeks of treatment, and the time of their onset was not related to INH. Body weight and age were factors related to the frequency of side effects [the higher the body weight, the lesser the rate of side effects (p = 0.03)] and the rate of serious side effects increased with age (p = 0.02). But, again, the frequency of the side effects was not related to INH administration. Therefore, from the present study it can be concluded that INH does not increase the toxicity of the thioamide containing treatment. PMID- 1299709 TI - Short-term trial of clofazimine in previously untreated lepromatous leprosy. AB - Forty-five previously untreated lepromatous leprosy patients were allocated randomly to three groups and treated, respectively, with Regimen A, standard dosage of clofazimine (CLO) in multidrug therapy (MDT) regimen; Regimen B, CLO 600 mg once every 4 weeks; and Regimen C, CLO 1200 mg once every 4 weeks. The duration of the trial was 24 weeks. By the end of the trial, although a few patients in each group did not improve at all clinically, the majority of patients showed clinical amelioration but the responses were slow. While the mean morphological index dropped to the baseline after 24 weeks of treatment, the mean bacterial index did not change significantly. About 80% of the patients in each group remained nasal-smear positive at the end of the trial, but the bacterial loads steadily declined. No significant difference has been detected in these parameters among the three groups. The patients tolerated the regimens very well and the side effects were mild. The results of serial mouse foot pad inoculation demonstrated that the positivity rates of multiplication of Mycobacterium leprae in mice and the proportions of viable organisms reduced gradually in all groups. Because the positivity rate at week 24 in Group C did not differ significantly from Group A, but was significantly smaller than that of Group B, we conclude that Regimen C was as active as Regimen A and could be applied for monthly supervised treatment along with rifampin; Regimen B is less effective and should not be used for the treatment of leprosy. PMID- 1299710 TI - A rapid and sensitive high performance liquid chromatographic analysis of clofazimine in plasma. AB - The high performance liquid chromatographic (HPLC) method of Gidoh, et al. has been modified substantially to provide a simple, rapid, and relatively inexpensive procedure for measuring clofazimine in plasma. The modification involves the use of commonly available laboratory reagents instead of custom-made ones. It also employs a solid phase system for efficient extraction instead of the conventional, less efficient and more labor intensive, liquid-liquid extraction. The inclusion of an internal standard (salicylic acid) improves the precision and reproducibility. It is demonstrated that the method can be used to monitor in vivo clofazimine levels as may be required in formal pharmacokinetic studies or therapeutic drug monitoring. PMID- 1299711 TI - Suppressive effect of circulating immune complexes from leprosy patients on the lymphocyte proliferation induced by M. leprae antigens in healthy responders. AB - The effect of circulating immune complexes, isolated in the form of polyethylene glycol (PEG) precipitates from leprosy patients, on lymphocyte proliferation was studied. The results obtained showed that PEG precipitates obtained from the borderline lepromatous/lepromatous (BL/LL) types of leprosy patients and those undergoing erythema nodosum leprosum (ENL) had significant suppressive effects on the lymphocyte proliferation induced by Mycobacterium leprae antigens in healthy responders. The percent decreases in the mean values of delta cpm in the presence of PEG precipitates from the BL/LL and ENL groups were found to be 46.8 +/- 22.4 and 65.0 +/- 24.3, respectively. However, no significant suppressive effects (except for ENL PEG precipitates) of these PEG precipitates were observed on the lymphocyte proliferation induced by tuberculin (PPD). Further, PEG precipitates alone (in the absence of M. leprae antigen) from the BL/LL and ENL groups were found to have no effect on the lymphocyte proliferation. PMID- 1299712 TI - Use of a different buffer system in the phenolic glycolipid-I ELISA. AB - By changing the buffer system in the phenolic glycolipid-I (PGL-I) enzyme-linked immunosorbent assay (ELISA) the sensitivity of the test was increased without altering its specificity. Using a Tris-HCl buffer, significant titers of > or = 1:300 were found in 53.1% of the sera in paucibacillary (PB) and 98.0% of the sera in multibacillary (MB) groups of patients. Titer levels were also significantly increased. In the PB group of patients with Tris-HCl, the highest titer detected was 1:1200; in the MB group of patients, 1:76,800. Through this modification of the buffer system a more sensitive test was obtained thereby increasing the detectable level of PGL-I antibodies in both the PB and MB groups of patients. PMID- 1299713 TI - Microtiter particle agglutination test for diagnosis of leprosy. AB - The results of studying the microtiter particle agglutination (MPA) test for detecting anti-Mycobacterium leprae antibodies in blood sera are presented. The serodiagnostic test is based on the agglutination of colored polyacrolein latex microparticles (PAMP) conjugated with 3,6-di-O-methyl-D-glucose (DMG). Sera from 45 leprosy patients (LL, BL), 34 leprosy contacts, and 148 control subjects were investigated by the MPA test. A correlation between the anti-M. leprae antibodies and the bacterial load was found. In many long-treated leprosy patients increased titers of anti-DMG antibodies were observed, which might be due to specific polyneuritis in them. Four contacts of leprosy patients were also positive in the MPA test. "Nonleprosy" sera did not react in the test. The method proposed proved to be of high specificity and sensitivity for the serological diagnosis of leprosy. The rapidity, simplicity, and visual assessment of the results allow the method to be used in the field for epidemiological studies of leprosy contacts and the general population in leprosy-endemic areas. PMID- 1299714 TI - Cold fingers in leprosy. AB - Under conditions of maximal thermoregulatory peripheral dilatation, most healthy subjects (both Indian and European) showed raised blood flow in the fingertips (measured by laser Doppler flowmetry) where the skin temperature is only slightly lower than the core body temperature. Most borderline lepromatous (BL) leprosy patients had much colder fingers and the blood flow was slow: borderline tuberculoid (BT) patients had skin temperatures similar to those seen in healthy subjects, but their fingertip blood flow was reduced relative to that in control subjects. The occurrence of cold fingers and slow blood flow was clearly associated with evidence of sensory impairment to light touch, pressure and temperature. Slower fingertip blood flow was strongly associated with impairment of vasomotor control in this anatomical region, suggesting that both may be a consequence of leprosy peripheral neuropathy, at least in patients with early leprosy, but it is likely that leprosy arteriopathy may contribute to the lowered peripheral perfusion in advanced cases. It is suggested that the simple clinical sign of cold fingers may be of value in the preliminary assessment of patients presenting at any leprosy control clinic in the tropics. PMID- 1299715 TI - Aspects of rehabilitation in leprosy. PMID- 1299716 TI - Erythema nodosum leprosum: a possible cause of oral destruction in leprosy. AB - Apart from vague statements and speculative remarks, the role of ENL in the oral cavity has not been considered in the recent English language literature. A case of oral ENL is reported, and we postulate that ENL plays a prominent role in the intra-oral destruction noted in leprosy. Information gathered from the literature and from our own experience with a series of 37 leprosy patients with oral lesions support this postulation. PMID- 1299717 TI - Consensus development statement on the chemotherapy of leprosy. American Leprosy Missions International and G. W. Long Hansen's Disease Center. PMID- 1299718 TI - About reactivation of the anti-hansenian programs through early detection of patients and systematic multidrug therapy. PMID- 1299719 TI - Modification of multidrug treatment of leprosy in Vanuatu. PMID- 1299720 TI - On reflections on the elimination of leprosy. PMID- 1299721 TI - Chromoblastomycosis masquerading as tuberculoid leprosy. PMID- 1299722 TI - Suitability of a skin-smear examination needle for leprosy screening by PCR. PMID- 1299723 TI - Genetic vaccines against genetically infective macromolecules? PMID- 1299724 TI - Inoculation of foot pads of severe combined immunodeficient mice with M. leprae. PMID- 1299725 TI - Adaptation of Mycobacterium psychrophilum (L) to mesophilic growth on water soluble palmitic acid complex agar media. PMID- 1299726 TI - Clinical impact of magnetic resonance imaging in foot osteomyelitis. AB - The impact of magnetic resonance imaging (MRI) on the clinical management of patients with foot inflammation and suspected osteomyelitis was evaluated in 44 patients with 47 foot MRI exams. Twenty-nine patients were diabetic. Bone biopsy or bone culture was obtained in 34 patients, and routine radiographs and bone scan studies were available in most patients for comparison. Magnetic resonance imaging showed reliable identification of bone infection with a sensitivity of 100% and specificity of 95%. Plain radiographs were inaccurate and, as expected, bone scans were highly sensitive (90%) but not specific (33%). The high accuracy of MRI allowed for better identification of patients with osteomyelitis and, therefore, improved targeting of potential operative candidates. PMID- 1299727 TI - Metatarsus adductus and selected radiographic measurements of the first ray in normal feet. AB - Radiographic evaluation of hallux abducto valgus frequently involves the measurement of the metatarsus adductus angle, first-second intermetatarsal angle, hallux abductus angle, and proximal articular set angle. While the concept that there is a relationship between untreated metatarsus adductus and hallux abducto valgus deformity is not new, a quantifiable relationship between the metatarsus adductus angle and intermetatarsal angle, hallux abductus angle, and the proximal articular set angle in normal feet is relatively undocumented. The purpose of this study is to document relationships between the metatarsus adductus angle and the other three measurements, and to establish normal values for the intermetatarsal angle, hallux abductus angle, and proximal articular set angle within metatarsus adductus angle subgroups. PMID- 1299728 TI - An unusual example of a calcaneus secondarius. PMID- 1299729 TI - Kohler's disease. PMID- 1299730 TI - First and second metatarsophalangeal joint dislocation. A case report. AB - A case of dislocated first and second metatarsophalangeal joints was reported along with the mechanics and mechanism of injury. The practitioner must be familiar with the mechanism of injury and radiographic classification to determine the proper indications for closed versus open reduction. The authors' review of the literature did not reveal a similar case involving a dislocation of the first and second metatarsophalangeal joints. PMID- 1299731 TI - Dermatitis artefacta. Case reports. AB - Patients who seek care for foot problems may present to the podiatrist with concurrent problems, such as anxiety, depression, phobias, personality disorders, and psychoses. These may or may not have any direct relationship to the pathogenesis of the foot problem. The podiatrist may learn of the presence of an emotional problem directly from the patient or from a family member. In many cases, the patient may be unaware or deny the presence of an emotional problem, leaving the podiatric physician in the dark about the patient's mental health state or its implications for the management of the skin problem. In a review of the psychosomatic aspects of dermatology, Koblenzer offered a working classification of the psychodermatoses. This is helpful to the podiatrist in recognizing those dermatologic disease states in which the various aspects of the individual participate in the disease, signs and symptoms of the disease, and the potential psychological value of the disease for the patient. It is also helpful to the podiatrist for recognizing those dermatoses in which psychiatric consultation may be useful so that recognition, treatment, improvement, and perhaps cure may be effected quickly. PMID- 1299732 TI - Antibiotics for children. PMID- 1299733 TI - Antibiotic prophylaxis in paediatric surgery. AB - Effect of antibiotic prophylaxis was studied in 400 children undergoing various types of surgery. Patients were divided into different classes according to the type of operation and each was further randomized into a routine or trial group. The routine group received antibiotics for prolonged periods. In the trial group, "clean" cases (class A) did not get any antibiotics. The "clean-contaminated" (class B) and "contaminated" cases (class C) received peri-operative antibiotics only. Frankly infected cases were not included in this trial. There were 131, 213 and 56 cases in classes A, B and C respectively; of these 13 (3.25%) cases were diagnosed as infected, four in the trial group and nine in the routine group. It was found that a short course of peri-operative antibiotics was equally, if not more effective. Prolonged courses of antibiotics were not only useless and expensive but could also be harmful. For clean cases there is no need for antibiotic prophylaxis. Children behave no differently and these results may be extrapolated to adults. PMID- 1299735 TI - Omeprazole in short term treatment of reflux oesophagitis. PMID- 1299734 TI - ECG and enzymatic indicators of therapeutic success after intravenous streptokinase for acute myocardial infarction--a pilot study. AB - The effect of intravenous streptokinase (SK) on time course of creatine kinase-MB (CK-MB) release and rapid reduction in ST-segment elevation as two non-invasive markers of reperfusion was prospectively studied in 83 patients with first anterior wall AMI (SK group, n = 61; control group, n = 22). CK-MB evidence of reperfusion in the SK group was significantly higher than that in the control group (80% versus 32%; P 0.0001). The rapid resolution of sum of ST segment elevations as an evidence of reperfusion was found in 82% patients in SK group versus 23% in the control group (P 0.0001). Both CK-MB and rapid resolution of ST segment elevations as evidences of reperfusion were found in 69% patients in SK and 14% in the control group (P 0.0001). The proportions of patients with non invasive evidence of reperfusion with half-dose SK (750,000 units) regimen were comparable to that reported in the literature with full dose SK (1.5 million) regimen. Thus, serial CK-MB and ECG analysis in patients with AMI undergoing streptokinase therapy provides a non-invasive means for assessing therapeutic success. A dose of 750,000 units of SK was found clinically satisfactory using previously validated non-invasive markers of coronary reperfusion and produced results previously reported with 1.5 million units of SK. PMID- 1299736 TI - Use of CLO test in the detection of Helicobacter pylori infection and its correlation with histologic gastritis. PMID- 1299737 TI - Vocal cord paralysis following endotracheal intubation. PMID- 1299738 TI - C-peptide; new diagnostic tool in the evaluation of hypoglycaemic and hyperglycaemic states. PMID- 1299739 TI - Immunological response in diabetes mellitus. PMID- 1299740 TI - Rational drug prescription policy. PMID- 1299741 TI - Reappraisal of intermediate-term follow-up of radiofrequency ablation of accessory atrioventricular pathways for treatment of Wolff-Parkinson-White syndrome. AB - To evaluate the safety and efficacy of catheter mediated radiofrequency (RF) ablation in patients with Wolff-Parkinson-White syndrome, 125 patients with accessory pathway (AP) mediated tachyarrhythmias underwent RF ablation. Right sided APs were ablated from the atrial aspect of the tricuspid annulus (all from the femoral vein approach) and the left-sided APs were ablated from the atrial or ventricular aspect of the mitral annulus. Immediately after ablation, 3 of 8 APs (38%) and 131 of 137 APs (95%) were ablated successfully with RF through a small tip (2 mm) and a large-tip (4 mm) electrode catheter, respectively. Seven of the 11 APs where RF ablation failed had a later successful DC ablation. During follow up (3 to 22 months), 11 of the 114 patients (10%) with successful ablation had return of accessory pathway conduction (2 had recurrence of tachycardia (2%)). Complications included transient myocardial injury (peak CK-MB 15 +/- 3 IU/l), transient proarrhythmic effects (more atrial and ventricular premature beats), accidental AV block (1 patient), cardiac tamponade (1 patient) and suspicion of aortic dissection (1 patient). In successful sessions, procedure and radiation exposure time were 3.8 +/- 0.2 h and 45 +/- 4 min, respectively. This study confirms that RF ablation with a large-tip electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome. PMID- 1299742 TI - Short- and mid-term follow-up results after percutaneous transvenous mitral commissurotomy. AB - This study reports the clinical follow-up for 6 months of 52 patients who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC resulted in an increase in mitral valve area from 1.1 +/- 0.3 to 1.7 +/- 0.4 cm2 (p < 0.0001), a decrease in mean left atrial pressure from 16 +/- 7 to 13 +/- 5 mmHg (p < 0.0001), and an increase in exercise time from 4.6 +/- 2.1 to 6.3 +/- 2.3 min (p < 0.0001). At 6 months follow-up, mitral valve area was unchanged (1.7 +/- 0.4 cm2). Of 52 patients, 33 showed clinical improvement and 19 had no clinical improvement after PTMC. Univariate analysis showed (1) younger age, (2) echocardiographic score of 8 or less, (3) existence of mitral regurgitation of less than grade 2 after PTMC, and (4) amelioration in left atrial dimension, mean pulmonary artery pressure and exercise time after PTMC as correlative factors for clinical improvement. In conclusion, PTMC was an effective procedure for mitral stenosis, especially in younger patients with an echocardiographic score of 8 or less. Change in left atrial dimension was a good indicator of the effectiveness of PTMC. PMID- 1299743 TI - Loss of nocturnal decline in blood pressure in diabetic patients with autonomic neuropathy. AB - We investigated loss of the nocturnal decline in blood pressure (BP) and its mechanism in diabetes mellitus with autonomic neuropathy (ANP). BP was measured every 30 min using ambulatory BP recorders in 52 diabetic patients and 11 nondiabetic controls. As an index of autonomic nervous dysfunction, CVRR (the coefficient of variation of the R-R interval on ECGs) and diastolic blood pressure response on standing were measured. Plasma volume (PV) was measured with RISA. The difference between daytime mean BP (09:00 to 13:00) and nighttime mean BP (01:00 to 05:00) was analyzed. The normal control group showed a significant reduction in mean BP during the nighttime (-12.8 +/- 7.5 mmHg) as compared with the DM group (-3.3 +/- 8.6 mmHg, p < 0.001). The diabetic patients with loss of the nocturnal decline in blood pressure showed autonomic nervous dysfunction and increased PV. In conclusion, the nocturnal elevation of blood pressure might result from an imbalance between reduced tone of sympathetic and parasympathetic functions in addition to the postural effect and increased plasma volume present in diabetic patients. PMID- 1299744 TI - Microvascular geometry of the rat heart. Arteriolar and venular capillary regions. AB - The importance of realistic data regarding microvascular geometry for the understanding of oxygen transport to tissue cannot be underestimated. The purpose of the present investigation was therefore to determine the pattern of capillarization in rat myocardium. The histochemical method used in this study was novel in that it allowed for the discrimination of arteriolar capillary (AC) and venular capillary (VC) regions on the basis of color. Our preeminent finding was that systematic differences exist in microvascular geometry from arteriolar to venular capillary regions in normal rat myocardium. Specifically, VC regions are characterized by greater capillary density; more uniform capillary spacing; shorter segment lengths; and increased capillary diameter. These differences translate to significantly greater capillary length, surface and volume densities on the venular side of the capillary bed. In the face of lower PO2 values towards venules, this distinctive geometry would serve to provide advantageous geometric conditions for oxygen diffusion. PMID- 1299745 TI - Cardioplegia with adenosine and adenosine triphosphate in the isolated guinea pig heart. AB - In order to determine the effect of adenosine triphosphate (ATP) and adenosine in cardioplegic solutions, a comparative study has been undertaken in isolated guinea pig hearts using the Langendorff perfusion technique as a model of cardiopulmonary bypass. The hearts (n = 10 in each group) previously being perfused by Krebs-Henseleit solution, were arrested by one of the following cardioplegic solutions: 1) Potassium 20 mM/L (Plegisol), 2) Potassium 20 mM/L+ATP 10 mM/L, 3) Adenosine 10 mM/L, 4) Adenosine 10 mM/L+ATP 10 mM/L. After 45 min of hypothermic ischemia, postischemic recovery of heart rate, ventricular contractility, heart work and postischemic changes in tissue enzymes (LDH, SGOT, SGPT) were compared among the 4 different cardioplegic solutions. Arrest time and number of arrest beats were also recorded and compared among the groups. Although similar beneficial results on postischemic recovery were achieved with adenosine cardioplegia and with ATP supplemented potassium cardioplegia, ATP supplemented adenosine cardioplegia did not show any beneficial effects on postischemic recovery. PMID- 1299746 TI - Effects of a new antiarrhythmic drug, SD-3212, on canine ventricular arrhythmia models. AB - The antiarrhythmic effects of a new antiarrhythmic agent, SD-3212, (-)-(S)-3,4 Dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylene dioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H-1, 4-benzothiazine hydrogen fumarate, were investigated using canine models of ventricular arrhythmias, i.e. spontaneously occurring digitalis-, two-stage coronary ligation and adrenaline-induced arrhythmias. SD-3212 suppressed adrenaline-induced arrhythmia and showed some antiarrhythmic effect on digitalis- and 48 hr coronary ligation-arrhythmias. These results indicate that SD-3212 has antiarrhythmic effects common among class IV antiarrhythmic drugs and also has additional efficacy common among class I antiarrhythmic drugs, thus when considering the level of experimental arrhythmias it somewhat resembles propafenone. It may therefore become a clinically useful antiarrhythmic drug among typical class I or class IV antiarrhythmic drugs. PMID- 1299747 TI - Hibernating myocardium associated with coronary artery dissection and vasospastic angina. AB - Hibernating myocardium is an uncommon clinical state involving persistently impaired myocardial function. A 61-year-old man was admitted because of vasospastic angina. Coronary angiography revealed coronary artery dissection in the midportion of the right coronary artery, and segmental vasoconstriction was evoked by acetylcholine. In this patient, hibernating myocardium in the dissected region was clearly demonstrated by dipyridamole thallium-201 imaging. This report describes the first documented case of hibernating myocardium associated with coronary artery dissection, and the usefulness of dipyridamole thallium-201 imaging in the assessment of this state. Coronary artery spasm might be relevant to the etiology of coronary artery dissection. PMID- 1299748 TI - Percutaneous transluminal coronary angioplasty in a patient with Kawasaki disease. A case report of an unsuccessful angioplasty. AB - A 13-year-old boy with severe coronary stenosis due to Kawasaki disease underwent percutaneous transluminal coronary angioplasty (PTCA). The guide wire and the balloon catheter easily passed through the stenosis in the left anterior descending artery. However, effective dilatation could not be achieved even when the balloon size was increased to 2.5 mm in diameter. We discontinued further inflation of the balloon because serious resistance was encountered on withdrawal of the balloon catheter. In patients with Kawasaki disease, the value of PTCA as a treatment for coronary stenosis is questionable. PMID- 1299749 TI - Alcohol-induced sinus bradycardia and hypotension in patients with syncope. AB - We observed 2 cases of repeated episodes of syncope after alcohol ingestion. Both patients were light drinkers and had carotid sinus hypersensitivity. In both cases, alcohol loading tests repeatedly induced sinus bradycardia and hypotension 1.0-1.5 hours after drinking alcohol. Atropine was effective in improving symptoms. A loading test using a glucose solution of equivalent osmolarity and volume was negative. Acute alcohol ingestion usually increases heart rate with variable effects on blood pressure. However, our 2 cases exhibited unusual alcohol-induced sinus bradycardia and hypotension, suggesting a paradoxical increase in parasympathetic activity and/or decrease in sympathetic activity. PMID- 1299750 TI - [The interleukin-1 content of the blood in patients with a pseudotuberculosis infection and opisthorchiasis]. AB - Interleukin-1 levels were measured according to S. B. Mizel in 25 patients with pseudotuberculosis and concomitant chronic opisthorchiasis and in 25 ones with pseudotuberculosis alone over the course of the disease and in 3 months after it. The controls were patients with chronic opisthorchiasis and normal subjects. Hyperproduction of interleukin-1 by peripheral blood monocytes was found in chronic opisthorchiasis patients and in pseudotuberculosis patients with concomitant opisthorchiasis over the entire follow-up period. In patients with pseudotuberculosis alone interleukin-1 production was found elevated only at the peak of the disease and during early convalescence, that was followed by a stable normalization of this characteristic. PMID- 1299751 TI - [Interleukin-1 production in patients with subacute and chronic opisthorchiasis]. AB - Interleukin-1 (IL-1) production by peripheral blood lymphocytes was studied in 3 patients with the subacute and in 28 patients with the chronic stage of the disease. Monocyte culture was obtained by the H. R. Recalde method, IL-1 activity was evaluated by the S. B. Mizel modification of the classic LAF-ASSAY. In the subacute stage of the disease IL-1 activity was 3.3 fold lower that in healthy controls and lower than in the total group of patients with chronic opisthorchiasis (Kact. 0.64 +/- 0.09, 2.12 +/- 0.17, 1.83 +/- 0.11, respectively, p < 0.01, p < 0.01). In those with the syndrome of chronic gastroduodenitis IL-1 production was lower than in patients with the syndrome of cholepathy (Kact. 1.55 +/- 0.18 and 2.03 +/- 0.16, p < 0.01). Immediately after praziquantel therapy IL 1 production fell from Kact. 1.82 +/- 0.13 to 1.18 +/- 0.06 (p < 0.01), but 5-6 months later the production of the cytokine normalized in convalescents. PMID- 1299752 TI - [A quantitative assessment of risk factors in helminthiases]. AB - Presents a quantitative assessment of some risk factors leading to enterobiasis and opisthorchiasis. Suggests a division of these factors into those that can be eliminated easily, conditionally, or not at all. PMID- 1299753 TI - [Differences in the dynamics of the eosinophilia, blood immunoglobulin E and the level of circulating immune complexes in patients with chronic opisthorchiasis treated with different doses of praziquantel]. AB - Sixty patients with a chronic Opisthorchis felineus infection were administered one-day therapy with praziquantel in doses 25, 40, or 60-75 mg/kg b. m. The former two doses of the drug did not much improve the levels of the examined immunologic parameters. In patients treated with the highest dose of praziquantel a significant decrease of the total and specific IgE and CIC levels, reaching that in the reference groups, was observed in 6-8 months after the treatment, this indicating a 92% efficacy of the drug in this group of patients. PMID- 1299754 TI - [The use of Wald's sequential alternative analysis for the differential diagnosis of trichinelliasis and leptospirosis in the initial period of the disease]. PMID- 1299755 TI - [The characteristics of the clinical course of taeniarhynchiasis and its combination with enterobiasis and lambliasis and fenasal treatment]. AB - A total of 276 patients with taeniasis alone and taeniasis associated with enterobiasis or lambliasis were involved in the study. The most prevalent features in patients of all the three groups were combinations of the painful, dyspeptic and astheno-vegetative syndromes, the least so--an isolated astheno vegetative syndrome. Combinations of these syndromes more frequently occur in taeniasis concomitant with enterobiasis (61% vs. 51% in taeniasis alone). Associations of taeniasis with enterobiasis or lambliasis are more frequently diagnosed in children. Combinations of the three syndromes were revealed in the patients with taeniasis coursing against the background of chronic gastritis, duodenal ulcer, cholepathies: in 79% vs. 33.3% in an uncomplicated course. Fenasal therapy for 3 days in a daily dose of 3 g proved fairly effective: 85.7 +/- 6.3% of adults and 82.6 +/- 6.4% of children recovered. PMID- 1299756 TI - [A new type of diphyllobothriasis foci in the Far East]. PMID- 1299757 TI - [The helminthiasis situation in the Republic of Belarus and the immediate tasks for its improvement]. PMID- 1299758 TI - [The resistance of Plasmodium falciparum strains to preparations of the 4 aminoquinoline series in the Republic of Guinea]. AB - In vivo measurements of P. falciparum sensitivity to chloroquine diphosphate, carried out in the Republic of Guinea, resulted in isolation of strains with degrees I and II resistance from 5 of the 25 examined patients, that may be due to a wide prophylactic administration of the drug to all patients with fevers without completing the course of therapy in all the patients infected. Such courses are obligatory to prevent the dissemination of chloroquine-resistant strains of the parasite and augmentation of the resistance. Further use of chloroquine and its analogs for the prevention and chemoprophylaxis of malaria in the Republic of Guinea appears still desirable, because the majority of P. falciparum strains are still sensitive to these agents. If no favorable changes are detectable in the clinical parameters of malaria patients in 4-5 days of chloroquine treatment or the condition recurs in 1.5-2 months, assessment of P. falciparum sensitivity to chloroquine is advisable, followed by a rational choice of the drug. PMID- 1299759 TI - [The current malariological situation in the countries of western Africa. 1. The Republic of Guinea]. AB - Favorable climatic conditions in the Republic of Guinea are conducive to a high prevalence of infectious and parasitic diseases, responsible for 70% of primary consultations of the population, malaria being diagnosed in 40% of cases. Five landscape malariologic zones were singled out in the country, that are characterized by a certain level of malariogenicity. In the lowland/river and mountain/river zones the parasite index of children aged 2 to 9 varied from 16.4 to 45%, and in some foci it reached 63.1%. Foci in the Guinea-Sudan type wet savanna zone are also referred to meso- and hyperendemic ones. The mountain/forest zones are mainly mesoendemic. Malaria foci in the forest/savanna zone in southern Guinea and in the Sierra Leone northern provinces are hyper- and holoendemic, with the parasite index of children aged 2 to 9 being 76.3-92%. PMID- 1299760 TI - [Foci of the rat mite Ornithonyssus bacoti (Mesostigmata, Macronyssidae) and rat mite dermatitis in Moscow]. AB - High density of the rat population in Moscow in 1990-1991 resulted in the appearance of Ornithonyssus bacoti foci and of cases of the rat-mite dermatitis in humans. A total of 36 foci of the disease were examined and eradicated. A method for the detection of such foci has been developed. Two types of foci are distinguished, communal and industrial, and their specific features as regards the rodent and mite populations and clinical features of dermatitis in humans are described. A system of measures for liquidation of foci of rat mites is suggested, including rat and mite eradication and treatment of the patients. Specific features of these measures for various types of foci and in case of a focus reappearance are enumerated. PMID- 1299761 TI - [A trial at using the systemic action of ivermectin for suppressing the vector capacity of ticks (Ixodidae) infected with the tick-borne encephalitis virus]. AB - Adult Dermacentor marginatus hatched from nymphs infected with TBE virus and poisoned with ivermectin retain their vector abilities. Even small individuals with a 1.5-2 times lesser mass as against the reference mass contain the virus in the body in the same titers and the virions in salivary gland alveoli. Administration of an oil solution of ivermectin into the stomach of white mice, nymph feeders, in a dose surpassing threefold the dose recommended for intramuscular injection of this agent completely suppressed shedding of intact nymphs but did not suppress it in those infected. The nymph mass, size and mass of adult ticks hatched from them dropped under the effect of ivermectin dosage build-up in both intact and infected ticks, but these processes were slower in ticks infected with TBE virus. The authors suggest that the ticks infected with TBE virus are much more resistant to the process of gamma-aminobutyric acid depression, the mechanism of ivermectin action. They emphasize the necessity of bearing in mind the possible differences in the reactions to systemic poisons of intact and infected ticks when organizing vector control measures. PMID- 1299762 TI - [An evaluation of the joint action of 2 species of entomopathogenic bacteria on mosquito larvae]. PMID- 1299763 TI - [A trial of breeding Anopheles stephensi Liston larvae]. PMID- 1299764 TI - [The insecticidal action of Fenax on the fleas of wild rodents]. PMID- 1299765 TI - [The clinical aspects of the problem of echinococcosis and the means for its resolution]. AB - The author assesses the basic clinical aspects of the problem of echinococcosis. Discusses the problems related to clinical realization of the invasion, clinical and morphologic parameters of the pathologic process development in echinococcosis, as well as problems in the diagnosis, treatment, and organization of the treatment-and-prophylaxis service in areas endemic for this condition. Outlines the major trends of further research of echinococcosis, that may be implemented at a new problem-solving unit that is to be created. PMID- 1299766 TI - [The attraction of taiga ticks by the smell of the host's fur in nature]. AB - In the "Zhigulevsky" preserve, 46 coarse calico napkins impregnated with 1 ml of an attractant, were placed alternatively as controls and experimental along the road with the interval of 5 meters. The attractant was a methanol wash-off of the hair of a mongrel dog. During 8 hour exposure the experimental napkins were attacked by 20% males and 12.5% females of active ticks living by the road (after the third experiment a complete catch of ticks was carried out). The tick distribution indirectly indicates that the attractant causes a increase of tick horizontal migrations up to 5 meters around the source of odour. The results obtained allow one to suggest a promising granulated attractive and acaricidal agent. PMID- 1299767 TI - [The variability of the itch mite Sarcoptes scabiei de Geer (Acariformes, Sarcoptidae) in relation to scabies epidemiology. 3. The geographical and seasonal variability]. AB - The statistical modes of individual variability of Sarcoptes scabiei females, developed and described by the authors in two previous papers, has been used to analyze the geographic, seasonal variability and to compare the mite populations with due consideration for the clinical features of the disease. Statistically significant differences in the size and proportion of the samples were found in Moscow, the Moscow region, and the town of Bishkek in spring and summer. A relationship was revealed between the degree of the female back chetoid cover joining and the disease duration, number of burrows in the skin integument and their sites. PMID- 1299768 TI - [Pathomorphological changes in the liver in experimental superinvasive opisthorchiasis]. AB - Experimental model of Opisthorchis felineus superinvasion was reproduced in 30 piglets aged 3 months. The pigs were infected by feeding them 100 g of sausage fish with the mean invasion intensity of 0.8-1 metacercaria per g of muscle tissue. A repeated infestation with a similar dose was carried out in a month. The invasion developed in 14 of the 30 animals. Histologic examinations of the liver, carried out in 2.5 months after the first infestation, have revealed diffuse persistent hepatitis in 9 animals and aggressive hepatitis in 4. Proliferative changes in the epithelium of the intrahepatic gall ducts with polyposis and diffuse focal infiltration of the wall mucosa with plasma and lymphoid cells, fibroblasts and eosinophils were found, characteristic of human opisthorchiasis. Pigs may be used as a model for experimental opisthorchiasis in research. PMID- 1299769 TI - [On the centenary of the birth of Varvara Petrovna Pod''iapol'skaia]. PMID- 1299770 TI - [Agranulocytosis--a complication of the chemotherapy of echinococcosis with mebendazole]. AB - Only two of the 75 patients with echinococcosis, treated with mebendazole in a dose of 50 mg/kg b. m. for 30 days (single course) and administered from 1 to 13 courses with intervals of 1 to 3 months, developed agranulocytosis eventuating in death in one female patient. Analysis of blood levels of mebendazole and its metabolites permits a hypothesis that high concentrations thereof may have a toxic effect on the bone marrow, inducing its hypoplasia, in subjects sensitive to these substances. PMID- 1299771 TI - [The EGF receptor pathway in human cerebral tumors]. AB - The epidermal growth factor receptor gene is the most frequently involved proto oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.F.) to tumor cells of the cystic wall has suggested investigation of possible "E.G.F.-like" autocrine activities in C.F. In 40% of gliomas, E.G.F.-R. gene is amplified and overexpressed. This is never observed in low grade astrocytomas. In 12% of the cases, mutations of the E.G.F.-R. gene are observed. In correlation with genomic abnormalities, E.G.F.-R. is immunoprecipitated in 40% gliomas. The basal phosphorylation of the receptor is increased in 50% gliomas. In C.F., unexpectedly, E.G.F.-R. phosphorylation inhibitory effect is observed. Its biochemical analysis suggests an anti-tyrosine kinase activity. The observation of anti-tyrosine kinase activity in C.Fs suggests the presence of negative modulatory factors of the proto-oncogene activation in tumor tissues. This could have therapeutical interest. PMID- 1299772 TI - [Giant cholesterol cysts of the petrous apex]. AB - In connection with their two own cases, the authors deal about the giant cholesterol cysts of the petrous apex. The lesions which are to be differentiated from epidermoid cysts are cholesterol granulomas. Their petrous apex location explains their characteristic large appearance. As each cholesterol granuloma, they occur when a bony cell is obstructed. This chronic obstruction induces mucosal edema then bleedings which lead to the formation and, by the lack of drainage, to the accumulation of cholesterol crystals. These crystals initiate a non specific reaction to foreign bodies, a granuloma, which also can bleed. Thus, a continuous cycle perpetuates the growth of the lesion. This lesion, when it is localized in the petrous apex, can reach a big size before the appearance of some signs. Usually, these are otologic (sensorineural hearing loss, tinnitus, vertigo) and/or cranial nerve palsies (V, VI, VII). C.T. scan (well defined, sharply marginated bony expansible lesion with isodense to the brain central part) and M.R.I. (central region of increased intensity on both T1 and T2 weighted images and peripheral rim of markedly decreased signal intensity in all instances) features are characteristic enough to allow diagnose with other petrous apex lesions (cholesteatoma, mucocele, epithelial cyst, histiocytosis X, ...). Surgical treatment must try to evacuate and to aerate the cavity or perhaps to obliterate it with fatty pieces in order to prevent the recurrence. PMID- 1299773 TI - [Role of embolization in the emergency treatment of ruptured cerebral arteriovenous malformations]. AB - Embolization of cerebral arterio-venous malformations (A.V.M.s) is nowadays recognized as belonging to the therapeutic panel applied to these lesions. After an hemorrhagic accident, embolization is most often performed several weeks later. We report three cases of intracerebral hematoma due to A.V.M. rupture (cortico-ventricular rolandic, lateral ventricle subependymal, cortical anterior temporal A.V.M.s). These were treated by endovascular methods, using fluid material (N.B.C.A.), in emergency or semi emergency (hours, days). This had been done for direct preoperative purposes or medical reasons (heparinization in thrombophlebitis). If, at Bicetre, the treatment of A.V.M.s by embolization is daily performed, this type of emergent treatment is rare (3 cases on the 350 patients treated till now). No complication was reported for these three patients. The efficiency of such an "emergent procedure" is unknown and cannot be compared to similar experiences. The empiric data we obtained make us think that embolization, necessarily done without heparin, is possible and may constitute an important help to surgery without delaying it. It reduces the risk of rebleeding by targetting the treatment on angio-architectural weakness points (false aneurysms). It redistributes the arterial blood, lowers the venous hyper pressure, improves the locoregional perfusion and finally leads to a better final neurological status. PMID- 1299774 TI - [Practical value of transcutaneous pressure adjustable valves (Sophy SU 8) in the treatment of hydrocephalus and arachnoid cysts in adults (75 cases)]. AB - The authors report a series of 75 adults treated over the four last years for hydrocephalus (69 cases) or arachnoid cysts (6 cases) by using a transcutaneous pressure adjustable valve (sophy SU 8) the mechanism of which is recalled. The shunt was ventriculo-atrial 46 times, ventriculo-peritoneal 23 times and cysto peritoneal 6 times. The opening pressure of the valve was initially adjusted 56 times in a medium, 9 times in a high, and 10 times in a low position, according to each particular patient's features. Following the evolution of the neurological status and/or the CT findings, the opening pressure was secondarily modified in 27 patients (i.e. in 36%), and in some of them several times. It was raised 16 times: 10 times because of subdural hydroma(s) (complicated with a subdural hematoma which required a surgical removal, in one case), and 6 times because of clinical symptoms of intracranial hypotension associated with hyper drainage signs on CT. It was diminished 20 times because of the absence of clinical improvement and persistence of dilated ventricles on CT. In these 27 patients the Sophy SU 8 valve allowed modification of its opening pressure according to the clinical and CT evolution, without need for reoperation. It is concluded that the patients who can benefit the more from this valve system are patients with normal pressure hydrocephalus or with arachnoid cysts. PMID- 1299775 TI - [14 cases of communicating syringomyelia associated with Chiari I malformation in children]. AB - The authors review their experience of 14 children with syringomyelia and associated Chiari I malformation observed during the last 21 years. Initial symptoms were motor weakness (57%), sensory signs (50%), scoliosis (50%) and bladder dysfunction (21.5%), while signs of admission were pyramidal signs (78.5%) with motor deficit (43%), spinal deformities (64.2%), syringomyelic syndrome (36%) and sensory deficit (21.5%). Four children were investigated with myelography, three with myelography and spinal CT Scan and the last seven cases with MRI. Ten children (71.4%) underwent a decompression of the Chiari malformation with or without drainage of the cyst and shunting of an associated hydrocephalus. Syringo-peritoneal shunts were used in 3 children and laminectomy with syringo-subarachnoid shunt in 1 case. The neurological symptoms improved in 57% of the cases, 2 patients deteriorated and 4 patients were lost to follow-up. The authors discuss the clinical symptomatology, the MRI study, the controversies concerning the treatment and concluded with their attitude concerning this pathology in children. PMID- 1299776 TI - [Epidermoid cyst of the corpus callosum]. AB - Epidermoid cysts are most commonly located in the cerebellopontine angle and the parasellar regions. The authors report a case of an epidermoid cyst of unusual location: it arises in the midline and involves the body of the corpus callosum with interhemispheric exophytic growth. Reviewing the literature they did not find any similar report. C.T. scan and M.R.I. are the methods of choice for establishing the diagnosis and differentiating between epidermoid cyst, dermoid cyst, lipoma and arachnoid cyst. M.R.I. is highly sensitive and is especially useful in determining tumour extension, particularly in the sagittal and coronal planes, essential for surgical treatment planning. Treatment should be complete surgical resection in order to avoid recurrence and chemical meningitis. PMID- 1299777 TI - [Cervicobulbar intramedullary lipoma. Apropos of a case with review of the literature]. AB - The authors report a case of cervical intramedullary lipoma extending into the bulbomedullary junction. 99 cases of cervical and/or dorsal intramedullary lipomas without spinal dysraphism, reported since 1884, are reviewed. There is poor correlation between lipoma's length and age of onset. Only lipoma extended to all the spinal cord begin in the first years of life. Clinical presentation is in 58% of cases a slowly compressive myelopathy, a syringomyelic syndrome in 9.5% of cases, a Brown Sequard syndrome in 6.5% of cases or atypical clinical features in 26% of patients. Finding of a subcutaneous lipoma at the level of the lesion helps for diagnosis. C.T. scan and magnetic resonance imaging (M.R.I.) precise lipomatous constitution of the tumor, its limits and relations with neighbouring tissues. Surgery is necessary when clinical features are advanced. Surgery indication is debatable when neurological manifestations are poor or absent. Post operative course is generally good and is not related with type of intervention. PMID- 1299778 TI - [Intramedullary neurinoma. Apropos of a case. Review of the literature]. AB - The authors present a case of intramedullary neurinoma. A 44 years old patient was admitted for lumbar pain and bilateral sciatica. Neurological examination was normal except for dysuria and diminution of Achilles tendon reflexes. Lumbar spine X-rays and spinal cord angiogram were normal, but myelogram and myelo-scan revealed a fusiform enlargement of the conus medullaris. MRI confirmed this aspect. Total removal of an intramedullary tumor was done, using ultrasonography, operating microscope and ultrasonic aspiration. The post-operative course was uneventful, with, as sequelae a perineal hypoesthesia. Histological examination of the excised tumor revealed a neurinoma. The epidemiology, clinical features, radiology, and surgical treatment of such rare intramedullary tumors are discussed. PMID- 1299779 TI - [Rapidly progressive glomerulonephritis (RPGN): from crescents to polynuclear activation]. PMID- 1299780 TI - The nosology of crescentic nephritis. PMID- 1299781 TI - [Crescent: structure, evolution, pathogenesis]. AB - Extracapillary crescent is an elementary lesion which can be superimposed to any type of glomerulonephritis, or constitute the main lesion as in vasculitis, or appear to be idiopathic. One must oppose cellular crescent which is partially reversible, to irreversible fibrous crescent. Cellular composition of crescents has been much controversial: initially considered as having an epithelial-cell origin, then an exclusive macrophagic origin, crescents are in fact composed of epithelial cells, monocytes-macrophages and lymphocytes all together. The former are prevailing when Bowman's capsule (BC) is intact, whereas macrophages predominate when there is extensive damage of GBM and of BC. The initial event in crescent formation appear to be breaches in glomerular capillary wall, leading the deposition of fibrin within Bowman's space. The consequence is the proliferation of parietal epithelial cells and of activated macrophages followed by a production, in series, of cytokines and growth factors. PMID- 1299782 TI - Glomerular crescents--composition and mediators. PMID- 1299783 TI - [role of cellular immunity in the genesis of rapidly progressive glomerulonephritis]. PMID- 1299784 TI - [Role of hemostasis in the formation of crescents in extracapillary glomerulonephritis]. AB - Extracapillary glomerulonephritis are associated with fibrin deposition in the urinary space of the glomerulus. Such deposits were correlated with the severity of the disease and with a poor renal outcome. Fibrin formation involves an activation of the coagulation cascade either through the intrinsic pathway, Hageman factor being activated by the altered glomerular basement membrane, either by the extrinsic pathway, infiltrating monocytes and glomerular cells exhibiting a procoagulant activity i.e. thromboplastin or tissue factor. Treatments with heparin or warfarin were shown to decrease the severity of experimental glomerular diseases. A similar beneficial effect was obtained with a monocyte-depleting serum and more recently with a treatment by a tissue type plasminogen activator. Glomerular cells also produce a fibrinolytic activity which could be too low or uneffective on extracapillary fibrin deposits if they contain high amounts of plasminogen activator inhibitors. Thrombin has procoagulant activity, antifibrinolytic activity and has cellular chemotactic and proliferative effects. It could play a major role in the pathogenesis of crescent formation. PMID- 1299785 TI - [Morphological basis of the classification of crescent glomerulonephritis]. PMID- 1299786 TI - [Serologic study of extracapillary glomerulonephritis]. PMID- 1299787 TI - [Rare specificity and mechanism of action of ANCA]. PMID- 1299788 TI - Rapidly progressive glomerulonephritis and Wegener's granulomatosis. AB - Wegener's granulomatosis is estimated at 1/100.000/year. Histological proof of the characteristic granuloma is only demonstrated in 1/3 of patients suspected of having WG. The ANCA test is essential in making the diagnosis. Wegener's granulomatosis can affect any organ system. That the beginning of the disease is restricted to one organ (limited WG) is postulated to be true in at least 1/3 of all patients. One peculiar organ manifestation of WG is the pulmonary-renal syndrome. Renal involvement in WG is common and can reach from pauci-immune mild mesangial to crescentic lesions, depending on the severity of the disease. Predictors of renal outcome are glomerular obsolescence and degree of tubulo interstitial lesions. PMID- 1299789 TI - [Micropolyarteritis]. AB - Micropolyarteritis are defined as necrotizing inflammatory lesion of the wall of small vessels affecting different organs. A necrotizing crescentic glomerulonephritis without immuno-deposits is observed in the kidney, frequently involved in this microscopic form of systemic vasculitis. Micropolyarteritis are regrouped with Wegener's syndrome and isolated pauci-immune necrotizing crescentic glomerulonephritis as "ANCA-related vasculitis", whose diagnosis is assessed throw renal biopsy and prognosis dependent on immuno-suppressive treatment. Sixty-one patients treated in our nephrology department for a RPGN during these ten recent years have been retrospectively studied. Among them, twenty-five patients presented clinical and morphologic aspects compatible with the diagnosis of micropolyarteritis. We present their clinical aspects and evolution under treatment. PMID- 1299790 TI - Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months. AB - No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders. PMID- 1299791 TI - Autoaggressive behaviour and cholesterol. AB - A retrospective analysis of a sample of 1,088 patients suffering from affective psychoses did not reveal associations between serum cholesterol and suicidal behaviour. However, suicide was associated with lower body weight. PMID- 1299792 TI - Examination of pre- and posttreatment MHPG during cognitive therapy. AB - Sixteen unipolar depressed patients were treated with cognitive therapy for 12 weeks. Pretreatment 24-hour urinary MHPG levels were unable to predict treatment response. There was a nonsignificant trend for cognitive therapy responders to show a decrease in MHPG during treatment when compared to nonresponders. PMID- 1299793 TI - Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients. AB - The efficacy of fluvoxamine was compared to that of amitriptyline in a double blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles. PMID- 1299794 TI - Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study. AB - The influence of delta sleep-inducing peptide (DSIP) on sleep was studied in 16 chronic insomniac patients according to a double-blind matched-pairs parallel groups design. Subjects slept for 5 consecutive nights in the laboratory. Night 1 was used for adaptation, night 2 for baseline measurements. In the afternoon before the 3rd, 4th and 5th night, half of the patients received intravenously 25 nmol/kg body weight DSIP, and half of the patients a glucose solution (placebo). Measures for sleep structure, objective (polysomnography) and subjective sleep quality and for subjective tiredness were assessed. The results for objective sleep quality indicated higher sleep efficiency and shorter sleep latency with DSIP as compared to placebo. One measure of subjectively estimated tiredness decreased within the DSIP group. Data analysis suggested, however, that the statistically significant effects were weak and in part could be due to an incidental change in the placebo group. As none of the other measures, including subjective sleep quality, showed any change, it was concluded that short-term treatment of chronic insomnia with DSIP is not likely to be of major therapeutic benefit. PMID- 1299795 TI - Effects of breakfast and caffeine on performance and mood in the late morning and after lunch. AB - The aim of the present study was to examine the effects of breakfast and caffeine on performance, mood and cardiovascular functioning in the late morning and after lunch. Forty-eight subjects were tested at 07.45 and subjects then assigned to one of the four conditions formed by combining caffeine and breakfast conditions. Subjects in the caffeine condition were given a dose of 4 mg/kg, the caffeine manipulation being double blind. At 11.15 subjects were given another coffee (subjects remained in the same caffeine condition) and had lunch at 12.30. Performance was examined prior to lunch (11.30) and after lunch (14.00). Effects of breakfast on recognition memory (lower false alarm rate) and logical reasoning (reduced accuracy) were found in the late morning but not after lunch. However, a semantic processing task was performed more slowly by the breakfast group after lunch. Caffeine improved performance on a sustained attention task, the logical reasoning task and semantic memory task. Subjects given caffeine also reported greater alertness and feelings of well-being, whereas the effects of breakfast on mood changed from the late morning to early afternoon. Few interactions between breakfast and caffeine conditions were obtained. PMID- 1299796 TI - Action of the N-methyl-D-aspartate receptor antagonist MK-801 against focal seizure activity from the feline hippocampus. AB - This study assessed the effects of MK-801 (0.1 and 0.5 mg/kg), a noncompetitive antagonist of N-methyl-D-aspartate receptors, on focal seizure activity elicited by electrical stimulation to the feline hippocampus. Neither afterdischarge duration nor behavioral seizure stage was significantly suppressed following intraperitoneal administration of MK-801 at two dose. Rather, MK-801 at a higher dose induced hippocampal seizure status in some of the cats tested. The present data suggest convulsant properties of MK-801 and limitations of its clinical utility as an antiepileptic agent. PMID- 1299797 TI - Topographical analysis of sleep spindle activity. AB - There is evidence for two types of sleep spindle activity, one with a frequency of about 12 cycles/s (cps) and the other of about 14 cps. Visual examination indicates that both spindle types occur independently, whereby the 12-cps spindles are more pronounced in the frontal and the 14-cps spindles in the parietal region. The purpose of this paper is to provide more information about the exact topography of these patterns. First the occurrence of distinct signals in anterior and posterior brain regions was verified using pattern recognition techniques based on matched filtering. Thus the existence of two distinct sources of activity located in the frontal and parietal region of the brain, respectively, was demonstrated using EEG frequency mapping. Evaluation of sleep recordings showed high stability both in the frequency and location of the presumed spindle generators across sleep. Pharmacological effects of lormetazepam and zopiclone on both spindle types were investigated. Both substances enhanced the sleep spindle activity recorded from the frontal and parietal electrodes, but this increase was more pronounced in the parietal brain region. PMID- 1299798 TI - Serum antibody responses to Streptococcus mutans antigens in humans systemically infected with oral streptococci. AB - Sera from patients with subacute bacterial endocarditis (SBE) due to Streptococcus mutans or other oral streptococci and from normal subjects were assayed by enzyme-linked immunosorbent assay for antibodies to defined S. mutans antigens. Antibodies of IgG and IgA isotypes to Ag I/II and Ag III were greatly elevated in S. mutans-SBE sera, and the IgA antibodies in 3 sera included both polymeric and monomeric forms. Elevated IgM and IgG anti-lipoteichoic acid and IgG and IgA anti-serotype c polysaccharide antibodies were also found. The sera of 4 of 6 patients infected with other oral streptococci also displayed antibodies to S. mutans Ag I/II. Sera of 3 patients infected with Streptococcus mitis or Streptococcus oralis, but none of the S. mutans-infected cases, showed elevated antibodies to human heart sarcolemma, and all SBE sera had elevated rheumatoid factor. These results suggest that the known surface protein antigens of S. mutans are immunodominant in humans, and are not likely to be heart cross reactive. PMID- 1299799 TI - Immunoglobulin A antibody activity to mutans streptococci in parotid, submandibular and whole saliva. AB - Antigen extracts of 9 strains of Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius and Streptococcus mitis were separated in acrylamide gels by electrophoresis. Strains of the same genotype of mutans streptococci were found to have virtually identical sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns but differed clearly from other genotypes of mutans or with the reference strains S. salivarius and S. mitis. Immunoglobulin A (IgA) antibody activity to antigens of S. mutans, S. sobrinus and S. mitis in the parotid, submandibular and whole saliva of 12 people was detected by Western blotting. IgA antibodies reacted with several of the antigens, and the reaction pattern was unique for each of the individuals. To certain antigens, all the salivas blotted bands if both clear and questionable bands were counted. Significantly more blotted bands were revealed with antigens from S. mutans than S. sobrinus. The results of the 3 different salivas of the same individual had a high degree of resemblance but in a few individuals, more blotted bands were obtained with parotid saliva to S. mutans and S. sobrinus antigens. PMID- 1299801 TI - Evaluation of the E test for antimicrobial susceptibility testing of Actinobacillus actinomycetemcomitans. AB - The E test was compared with an agar dilution method for antimicrobial susceptibility testing of Actinobacillus actinomycetemcomitans on Mueller-Hinton Haemophilus test medium. Eighty recent isolates of A. actinomycetemcomitans from 40 subjects and 3 reference strains were studied. Excellent agreement was obtained between the E test and the agar dilution test for benzylpenicillin (98.8%), ampicillin (97.5%), cefaclor (100%), cefuroxime (100%), tetracycline hydrochloride (100%) and ciprofloxacin (98.7%); 76.0% agreement was obtained for metronidazole and only 5.2% for cotrimoxazole. This study indicates that the E test is a reliable method to determine minimal inhibitory concentrations of antimicrobials against A. actinomycetemcomitans, except for metronidazole and cotrimoxazole. PMID- 1299800 TI - Immunosuppressive effect induced by Actinobacillus actinomycetemcomitans: effect on immunoglobulin production and lymphokine synthesis. AB - The soluble sonicated extract (SE) from Actinobacillus actinomycetemcomitans inhibited primary T cell-dependent antibody responses in vivo. The production of IgG and IgM to sheep red blood cells (SRBC) was depressed when mice were treated with high concentrations of SE plus SRBC. Preinjection of SE 3 days prior to SRBC completely inhibited IgG production. SE plus SRBC-primed mice showed markedly depressed CD4/CD8 ratios relative to phosphate-buffered saline plus SRBC- or SRBC immunized mice. SE-sensitized mice showed low blastogenic activity to concanavalin A (Con A) depending on sensitized periods induced by SE. This inhibitory mechanism was, in part, clarified by a suppression of IL-2 synthesis, IL-2 receptor expression and IL-6 secretion by the splenic T cells stimulated with Con A. These results support the hypothesis that the severe infection of A. actinomycetemcomitans suppresses the immune response by affecting CD4/CD8 ratios, followed by lymphokine production and finally antibody responses. PMID- 1299802 TI - Hydrogen sulfide and methyl mercaptan in periodontal pockets. AB - A sensitive gas chromatographic method was developed to determine the amounts of volatile sulfur compounds in gingival fluid. Hydrogen sulfide was the predominant volatile sulfur compound and was detected in 61 out of 79 studied periodontal pockets. Methyl mercaptan was found in about 20% of the pockets. No other volatile sulfur compounds were detected. The highest concentration of hydrogen sulfide in gingival fluid was 1.9 mmol/liter, and of methyl mercaptan 0.16 mmol/liter. PMID- 1299803 TI - [The biology of the thorny-headed worms, parasites of trout acclimatized in the bodies of water of the Tien Shan]. AB - A new species of Acanthocephala, a parasite of local Naemacheilus stoliczkai, was recorded from Salmo gairdneri after 9 years of its introduction into mountain water bodies of Tien Shan. Gammarus lacustris serves as an intermediate host. Dynamics of infection of trout for 9 years is shown. PMID- 1299804 TI - [Fish parasites as bioindicators of the pollution of bodies of water]. AB - The paper presents the results of studies on the effect of wastes of the Cherepovets iron-and-steel works containing phenol, naphthaline and oil products on fish parasites of the Sheksna part of the Rybinsk water reservoir (the Volga river system). It has been shown that the number of highly sensitive ectoparasites of Abramis brama (Protozoa, Dactylogyrus monogeneans, Ergasilus sieboldi crustaceans and Caspiobdella fadejewi leeches) considerably decreases in the zone of pollution. It has been first suggested to use Diplozoon paradoxum and Caryophyllaeus laticeps, parasites of bream highly resistant to toxic effect, the number of which considerably increases in the zone of pollution, as indicators of anthropogenic pollution and ecological state of a water body. Among diplozoons there have been first discovered individuals having structural anomalies (reduction of the attachment organs, violation in the symmetry of arrangement and number of valves) that serves as evidence of mutagenic effect of toxic substances of polluted waters on morphogenesis of the parasite. PMID- 1299805 TI - [Differences in the distant transmission of the tick-borne encephalitis virus by ixodid ticks of 2 subfamilies]. AB - Simultaneous but separate feeding of ticks on nonviremic animal (guinea pig) has shown that Amblyomminae ticks are practically unable to transmit distantly tick borne encephalitis virus (TBEV) to the specimens of their own subfamily and to Ixodinae as well. Ixodes persulcatus and I. ricinus displayed their ability as donors and recipients of TBEV (adults and nymphs) not only for their own subfamily representatives but also as donors for recipients of Amblyomminae subfamily (nymphs and adults of Dermacentor and Rhipicephalus and nymphs of Haemaphysalis). Experimental and literature data analysis permits the authors to conclude that the very important role of TBEV circulation in nature belongs to the distant virus transmission. The absence of such type of virus exchange among Amblyomminae excludes this group of ticks from active virus circulation in TBEV foci. PMID- 1299806 TI - [Notes on fleas (Siphonaptera) in plague foci on the Tay Nguyen plateau (Vietnam)]. AB - The fleas of wild and commensal small mammals, domestic animals (dogs, cats) and free-living flea forms in houses have been collected in plague nidi of Tay Nguyen plate, Dak-Lak province, Vietnam. Pulex irritans, Ctenocephalides felis felis, Ct. felis orientis were found in the houses on dogs, cats and on the ground floor. Commensal rats in populated areas were infested by Xenopsylla cheopis and rarely by Lentistivalius klossi. The agricultural zone was inhabited by both home and wild animals such as commensal, savannah and forest-dwelling small mammals. The flea fauna of this zone is presented by X. cheopis and L. klossi. In the tropical forest surrounding villages four of the flea species were found: X. vexabilis, a specific parasite of the forest-dwelling rat Berylmys berdmorei, L. klossi found on six species of forest small mammals, Acropsylla girshami from Berylmys bowersii and Pariodontis subjugis from Hystrix brachyura. The agricultural zone is the most possible place of commensal and forest-dwelling small mammals contact, where the latter can get plague microbe. PMID- 1299807 TI - [Increase of excretion of urinary catecholamines and its catabolites in a case of pulmonary sarcomatous tumor]. AB - A five-year-old child presented with a large undifferentiated sarcoma in the right lung. Urinary catecholamines were assayed as tumor markers. A short-lived but significant rise in urinary norepinephrine and dopamine followed by rises in urinary levels of corresponding breakdown products were evidenced. PMID- 1299808 TI - [Markers for smoking]. AB - Quantitative and objective measurement of exposure to cigarette smoke by assays of chemical markers is desirable, especially in preventive medicine, since the negative health effects of tobacco smoke are well documented. Chemical markers include nicotine and cotinine in plasma, urine, and saliva; carbon monoxide in exhaled air; carboxyhemoglobin in blood and thiocyanate in biological fluids. Ease of use, cost, specificity, and sensitivity vary across markers. Determination of the thiocyanate/creatinine ratio in urine is a reliable, noninvasive, and inexpensive test for evaluating exposure to cigarette smoke. No marker for cumulative exposure to cigarette smoke is available to date. The plasma level of fluorescent lipoperoxides may provide an estimation of the in vivo toxicity of exposure to cigarette smoke. PMID- 1299810 TI - [Immunotherapy of severe gram-negative bacterial infections. Centoxin: a new drug under monitoring. National Committee for the Evaluation of Centoxin]. PMID- 1299809 TI - Echinomycin. AB - The story of echinomycin is of an antibiotic whose anti-cancer activity was rediscovered thanks to scientific investigation of its mode of action at the molecular level. It was the first DNA bis-intercalator identified (in 1974). Molecular models for echinomycin and its congeners are now well-founded on crystallographic data. These are beginning to throw light on significant variations in conformation which affect the ability of the antibiotics to recognise specific nucleotide sequences in DNA. Kinetic and other physical experiments have revealed much about the stability and selectivity of antibiotic DNA complexes: stacking forces are important, as are hydrogen bonding interactions. Echinomycin preferentially recognises sites in DNA containing the CpG step, but other sites of lower occupancy exist and the antibiotic can migrate between them. Currently a good deal of attention is being paid to the suggestion that echinomycin might change Watson-Crick base pairs to a Hoogsteen form. PMID- 1299811 TI - [Genetics of non-insulin-dependent diabetes mellitus: the end of the nightmare?]. PMID- 1299812 TI - [AIDS, management of professional risk and reorganization of nursing care]. PMID- 1299813 TI - [Occupational risk of exposure to blood in nurses. Results of a one-year monitoring of the risk for nurses in 17 hospitals]. AB - To evaluate the incidence of risk factors for exposure of health care providers to patients' blood, a prospective multicenter study was carried out in 1990 in 17 hospitals in continental France. 521 nurses from 20 departments of medicine and 9 intensive care nurses participated in the study. Trained investigators documented exposures to blood using a standardized questionnaire and carried out monthly 24 hours cross-sectional surveys to determine the number of high risk procedures performed on a given day. One hundred and eighty-three exposures to blood were documented, for an incidence of 0.35/nurse/year. Needle-stick injuries were the most common events (75%). Exposure to blood occurred during a sampling procedure in 48% of cases, an infusion-related procedure in 20% of cases, and an injection in 17% of cases. Comparisons of rates of procedures associated with needle-stick injuries and of procedures performed during a typical day demonstrated differences in the magnitude of the risk associated with each procedure: infusion related procedures carried the greatest risk, followed by venous blood sampling procedures. Sixty-four percent of exposures to blood occurred after completion of the procedure. Forty-nine percent of documented exposures to blood would probably not have occurred if universal infection control recommendations (CDC, DGS) had been implemented. Twenty-seven percent of exposures to blood involved HIV positive patients, who accounted for only 7% of patients managed in the participating centers during the study period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299814 TI - [Study of the ototoxicity of amikacin and netilmicin using provoked acoustic oto emissions and high-frequency audiometry]. AB - To compare the ototoxicity of amikacin and netilmicin, tone audiometry, high frequency audiometry, early auditory evoked potentials, and evoked otoacoustic emission testing were used to evaluate 30 patients (15 under amikacin and 15 under netilmicin). Ototoxicity was not significantly different in the two groups. PMID- 1299815 TI - [Study of ninety strains of serogroup A Neisseria meningitidis isolated from cerebrospinal fluid (25) and rhinopharynx (65) in Morocco (December 1989-April 1990)]. AB - Ninety strains of Neisseria meningitidis were recovered from cerebrospinal fluid and nasopharyngeal specimens during the outbreak which occurred in Morocco between December 1989 and April 1990. All the strains recovered belonged to serogroup A. Serotype determination carried out using the "whole cell ELISA" method showed that all strains were serotype 4, subtype P1.9. Antigenic formula of the strains was therefore A:4:P1.9. Electrophoretic characterization of outer membrane proteins demonstrated proteins belonging to classes 1, 3, 4, 5 and 6, with a few rare exceptions which are discussed. PMID- 1299816 TI - [Activity of ethambutol, isoniazid and rifampicin on Corynebacterium urealyticum and Corynebacterium jeikeium]. AB - Because corynebacteria and mycobacteria have walls of similar composition, it was of interest to test the effects on resistant corynebacteria of two agents with anti-wall effects, i.e., ethambutol (EMB) and isoniazid (INH). Rifampicin was also studied to extend previous data and clarify conflicting results in the literature. INH was not active in levels achieved in vivo with standard dosages. The minimal inhibitory concentration (MIC) of EMB was under serum levels for only three of 78 strains. All minimal bactericidal concentration (MBCs) were greater than serum levels. With RIF, 59% of strains were susceptible and 19.2% exhibited intermediate susceptibility as defined by the French Committee on Antimicrobial Susceptibility Testing. CMI and CMB distributions were heterogeneous, suggesting a possible acquired heterogeneous resistance to RIF. PMID- 1299817 TI - The rediscovery of hal. PMID- 1299818 TI - Effects of psychoeducational care for adult surgical patients: a meta-analysis of 191 studies. AB - A quantitative review of the literature (meta-analysis) was conducted with 191 studies of the effects of psychoeducational care on the recovery, postsurgical pain and psychological distress of adult surgical patients. Studies issued between 1963 and 1989 were included in the review. Statistically reliable, small to moderate sized beneficial effects were found on recovery, postoperative pain and psychological distress. In further analyses it was shown that these beneficial effects were not an artifact of the biases associated with the decision whether to publish a paper, low internal validity, measurement subjectivity, or a Hawthorne effect. The overall efficacy of psychoeducational care provided to adult surgical patients has been reconfirmed with this larger sample of studies. It is particularly noteworthy that these findings are of more than strictly historical interest. Despite changes in health care delivery, beneficial effects continue even in studies issued between 1985 and 1989. Implications for clinical practice are drawn. PMID- 1299819 TI - A meta-analysis of controlled trials of cardiac patient education. AB - Because of the heavy burden of morbidity and mortality exacted by coronary heart disease and the role of behavior in secondary prevention, patient education is a crucial part of cardiac care. Yet evaluations of such programs have not been synthesized to assess the average effects nor which program characteristics have greatest impact. This study used the quantitative methods of meta-analysis to answer these questions, with 28 controlled studies measuring behavioral and clinical outcomes. Results indicate that cardiac patient education programs have demonstrated a measurable impact on blood pressure, mortality, exercise, and diet, other parameters are positively affected, although less consistently. Type of communication channel did not influence outcome; adherence to educational principles did. Thus, cardiac programs should use reinforcement, give feedback, offer opportunity for individualization, facilitate behavior change through skills and resources, and be relevant to patients' needs and abilities. PMID- 1299820 TI - Approaches to patient and family education with affective disorders. AB - This paper provides an overview of prevalence, types, effects and treatment for affective disorders, with particular emphasis on educational and psychoeducational interventions. It reviews several models of psychoeducation including the approaches used in various programs at the Psychiatric hospital in which the authors work. These approaches are based on the Psychoeducational Model of Family Treatment developed by Dr. Carol Anderson and colleagues. Outcome data from several studies are also presented evidencing the positive impact of these interventions on patients and families. PMID- 1299821 TI - Characteristics of controlled studies of patient education and counseling for preventive health behaviors. AB - To determine characteristics of controlled studies (quasi-experimental and randomized) of clinical patient education/counseling for behavior change to prevent disease, we conducted an extensive literature review of published and unpublished studies from 1971 to 1989. Sixty-four studies with 101 intervention groups met specific criteria for relevance and scientific acceptability. We examine these studies in terms of prevention area, subject source, intervention characteristics, and use of educational principles. Findings reveal many controlled clinical studies in smoking cessation, nutrition, and weight control but sparcity in other areas (injury prevention, exercise, stress, drug and alcohol misuse, STD prevention); an emphasis on communication by a single clinical practitioner; and varied use of educational principles. We recommend adhering to educational principles to enhance likelihood of success. PMID- 1299822 TI - Methods of psychoeducational program evaluation in mental health settings. AB - Psychoeducational programs for families of the mentally ill became widespread during the 1980s as a means of providing a forum for the relevant education and mutual support of participants. While these programs are thought to be extremely useful as interventions, very little emphasis has been placed on evaluation as a means of demonstrating their effectiveness in achieving goals. There is a possibility, then, that psychoeducation will continue to flourish with little direct evidence of positive outcomes for its family participants. This article consists of a literature review of existing methods of psychoeducational program evaluation, both quantitative and qualitative, all of which may be applicable in certain circumstances. The process by which an evaluation instrument was developed for a program with families of the mentally ill is then presented in some detail. PMID- 1299823 TI - HIV/AIDS knowledge and awareness of testing and treatment--Behavioral Risk Factor Surveillance System, 1990. PMID- 1299824 TI - Capacitation and its sequelae. PMID- 1299825 TI - Abnormalities of human preimplantation development in vitro. PMID- 1299826 TI - FSH and LH receptor concentrations in large ovarian follicles of beef cows in high and low levels of body condition at nine weeks post partum. AB - An experiment was conducted to determine whether or not the effect of body condition at parturition, and thereafter, on the duration of the post-partum anoestrous period was mediated through differences in gonadotrophin receptor concentrations in the ovarian follicles. Two groups of cows were fed to achieve body condition scores of > or = 2.75 (H; n = 14) or < or = 2.00 (L; n = 15) at parturition (this had led to differences in the duration of post-partum anoestrus in previous experiments) and then fed to maintain liveweight and condition until ovariectomy at nine weeks post partum. There was no effect of body condition on the mean (+/- s.e.) number of large (> or = 8 mm diameter) follicles per cow (3.0 +/- 0.27) but a greater proportion of the follicles of H cows, compared with L cows, was oestrogenic (secreting > 250 pg oestradiol h-1 in culture) (0.75 v. 0.5; chi 2 = 3.40; P = 0.06). Mean concentrations (pg hormone bound per mg protein) of follicle stimulating hormone (FSH) receptors in both granulosa (H, 157.3; L, 136.6; standard error of difference (s.e.d.) = 27.2) and thecal tissue (H, 4.14; L, 4.35; s.e.d. = 1.66) were similar for H and L cows. There was no difference associated with treatment in luteinizing hormone (LH) receptor concentrations in either granulosa (H, 40.3; L, 37.2; s.e.d. = 6.67) or thecal tissue (H, 48.9; L, 48.0; s.e.d. = 6.03). The concentration of FSH receptors in granulosa tissue was lower in non-oestrogenic follicles than in oestrogenic follicles (80.0 v. 188.1; s.e.d. = 40.4; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299827 TI - Studies on the reproductive performance of Ethiopian sheep by means of an enzyme immunoassay technique; a review. AB - Measurement of the concentration of hormones associated with reproductive function in female animals can aid in the evaluation of their reproductive status. In particular, from the point of view of production, determination of the concentration of circulatory progesterone can aid in the correct assessment of ewes. Many investigators have used radioimmunoassay for this purpose, but the enzyme-linked immunosorbent assay (ELISA) is equally reliable, quicker and cheaper. This report reviews the use of the ELISA in Ethiopian Menz sheep. Progesterone profiles in Ethiopian Menz sheep during pubertal development, the oestrous cycle, pregnancy and post-partum anoestrus were similar to those of temperate breeds. The practical applications of progesterone determination to sheep production and the requirement for the correct handling of samples are emphasized. PMID- 1299828 TI - Protein synthesis and secretion by the epididymis of the tammar wallaby, Macropus eugenii (Macropodidae: Marsupialia). AB - The objectives were to assess the following in a marsupial: which proteins are synthesized by the different regions of the epididymis and secreted into the lumen of the ductus; the effect of the experimental method on the detection of protein secretion; the role of the testis in regulating the protein synthesis and secretion; and whether any of the secreted proteins may associate with spermatozoa. Samples from untreated animals were collected for examination by perfusing Krebs-bicarbonate through the ductus epididymidis in vivo (microperfusion), and after incorporation of [35S]methionine during incubation of minced duct in vitro. Electrophoresis of the samples showed that the caput and corpus epididymidis (initial segments) secreted most of the proteins that were synthesized and secreted by the epididymal mucosa, and that the cauda epididymidis secreted mainly blood proteins. Also, many more proteins were secreted in vitro than into the microperfusates in vivo, or were found by Jones (1987) in micropuncture samples of epididymal plasma. The synthesis and secretion of five proteins was androgen dependent (M(r) 75,700, 30,000, 18,700, 17,400 and 12,800). Also, the luminal fluids from the testis stimulated the secretion of two proteins (M(r) 46,300 and 36,100) and inhibited the secretion of three proteins (M(r) 43,000, 32,300 and 21,400). Examination of detergent extracts of spermatozoa indicated that they lose three proteins (M(r) 28,000, 30,000 and 47,000) and gain one (M(r) 30,400) during passage through the epididymis. The method of determining protein secretion affected the findings. Protein secretion, its control and its association with spermatozoa are broadly similar in the tammar wallaby to the processes described in eutherian mammals. PMID- 1299829 TI - Developmentally related changes in the uptake and metabolism of glucose, glutamine and pyruvate by cattle embryos produced in vitro. AB - The metabolism of, and retention of radioactivity from, radiolabelled glucose, glutamine and pyruvate were measured in individual cattle embryos produced in vitro from the 2-cell to hatched blastocyst stage. Uptake was defined as the numeric sum of metabolism and retention of radiolabel. Glucose metabolism increased significantly between the 8- and 16-cell stages, but was accompanied by a much larger increase in glucose uptake. Consequently, the proportion of glucose uptake that was metabolized through the pentose-phosphate and Embden-Meyerhof pathways reached a minimum at those stages. From the compacted morula stage onward, the calculated uptake of [14C]glucose was only 25 to 33% of that calculated for [5-3H]glucose. This suggests that 66 to 75% of glucose carbon leaves the embryo, after metabolism to phosphoenolpyruvate, in some form other than CO2. Little or no glucose metabolism by the Krebs cycle could be detected at any stage. Both glutamine and pyruvate metabolism were relatively high at the 2- and 4-cell stages, declined to a minimum at the compacted morula stage and then increased with blastulation. Glutamine metabolism continued to increase with expansion and hatching of the blastocyst, but pyruvate metabolism did not. This suggest that, relative to the activity of the pathway from pyruvate to 2 oxoglutarate, the activity of the 2-oxoglutarate-to-oxaloacetate segment of the Krebs cycle is of increasing significance during expansion and hatching of the cattle blastocyst. PMID- 1299830 TI - Interaction of ovary lectin with homologous sperm from Bufo arenarum. AB - A soluble beta-galactoside lectin purified from Bufo arenarum ovary agglutinated homologous neuraminidase-treated spermatozoa. Microscopic observations of sperm clusters showed that spermatozoa agglutinated in a random way, but the head-to head type of sperm agglutination was the most common (94-98%). The lectin activity was specifically inhibited by D-galactose and its derivatives, thio digalactoside being the most active saccharide inhibitor. PMID- 1299831 TI - Timing of the window of uterine sensitivity to decidual stimuli in mice. AB - The refractory period that follows the period of sensitivity to a decidual stimulus in ovariectomized hormone treated mice was investigated. Medroxyprogesterone acetate provided constant progestin concentrations and silastic implants containing oestradiol maintained constant nidatory oestrogen concentrations. The nidatory stimulus was provided by crushing the uterus with a haemostat or by the intrauterine instillation of arachis oil. The decidual response was assessed by measuring changes in uterine weight or by examining the stroma for the presence of alkaline phosphatase. Sensitivity to the oil was first observed approximately 14 h after the insertion of the oestradiol implant but this sensitivity had waned by 32 h and was absent at 40 h. Crushing the uterus initiated a decidual response in mice treated with progestin alone but if the oestradiol implant was inserted then the uterus was responsive to crushing 24 h after insertion but not at 45 h. The traumatic decidual cell reaction (crushing), although not requiring nidatory oestradiol for its successful initiation, was nevertheless subject to the refractoriness that followed oestradiol sensitivity. PMID- 1299832 TI - Evaluating an in vitro culture system of bovine uterine and oviduct epithelial cells for subsequent embryo co-culture. AB - Three experiments were conducted to evaluate the effects of culture medium and incubation temperature on bovine uterine and oviduct epithelial cell growth, so that the most efficient combination could then be used to develop a co-culture system for bovine embryos. In the first experiment, uterine and oviduct epithelial cells at either the second or third subpassage were incubated for 8 days at 37 degrees C with 5% CO2 in Tissue Culture Medium-199, CMRL-1066, Minimal Essential Medium, Menezo's B2 or Ham's F-12 medium. In addition to plotting growth curves of cell populations, the cell cycle was monitored for 8 days by flow cytometry. Uterine and oviduct epithelial cells incubated in CMRL-1066 exhibited the highest growth rates during the 8-day culture period. However, there were no differences in cell cycle analysis among treatment groups during the incubation period. In the second experiment, CMRL-1066 medium was used to evaluate growth and proliferation of uterine and oviduct epithelial cells incubated at 37 degrees C or 39 degrees C; temperature had no significant effect on growth rates or proliferation rates for either uterine or oviduct cells during the 8-day incubation. In the third experiment, the more promising culture media for epithelial cell culture studies were chosen for in vitro maturation and subsequent in vitro fertilization (IVF) of bovine oocytes. Early cleavage-stage embryos produced by IVF procedures were subsequently cultured in vitro for 7 days in medium alone or with oviduct epithelial cells. In this study, the culture medium did not influence fertilization or cleavage rates. However, more embryos co-cultured with oviduct epithelial cells were considered viable after 7 days of incubation compared with embryos incubated in medium alone. These results indicate that various incubation conditions can influence the growth of bovine uterine and oviduct epithelial cells in vitro. However, in spite of changes in cell growth patterns, there does not appear to be a change in their embryotropic capabilities in vitro. PMID- 1299833 TI - Effect of late pregnancy serum on the synthesis and release of pregnancy proteins by the perfused human term placenta. PMID- 1299834 TI - GIFT or IVF for patients with patent fallopian tubes? AB - The pregnancy rate in a group of 39 couples who underwent in vitro fertilization (IVF) with donor sperm was compared with that of couples undergoing gamete intra Fallopian transfer (GIFT) over the same period (31 December 1986 to 30 June 1991). The diagnostic status of the female partners in each group was qualitatively similar. The women had patent Fallopian tubes, mild endometriosis or minor tubal adhesions. The male partners in the GIFT group had normal or marginally abnormal semen parameters which were considered to be comparable to the post-thaw quality of the semen used in donor insemination (DI). The mean age of the women in the DI group was 32 years (range 25-40) which was similar to that in the GIFT group [32 years (24-39)]. The women in the IVF group had undergone a mean of eight cycles of DI before proceeding to treatment with IVF. There was no difference between the pregnancy rate in the two groups (log-rank test). These observations advance the proposition that IVF should be reconsidered as an effective treatment for women with patent Fallopian tubes. PMID- 1299835 TI - Oxytocin delays oestradiol-induced luteolysis but does not affect oestradiol induced luteinizing hormone secretion in the ewe. AB - Circulating concentrations of progesterone, the prostaglandin F2 alpha (PGF2 alpha), metabolite 13,14-dihydro-15-keto PGF2 alpha (DHKF2 alpha) and luteinizing hormone (LH) have been measured in cyclic ewes receiving a continuous infusion of oxytocin, in order to investigate the effect of maintained concentrations of circulating oxytocin on the luteolytic action of oestradiol-17 beta. Oxytocin (3 nmol h-1 intravenously) was given from Day 7 until Day 17 after oestrus with oestradiol-17 beta (2.76 mumol, intramuscularly in sesame oil, 0.5 mL-1) administered on Days 9 and 10. Control ewes, given a continuous infusion of saline (154 mmol L-1, 3 mL-1 h-1) and sesame oil on Days 9 and 10, underwent luteal regression at the expected time, with mean concentrations of plasma progesterone falling to below 1.5 nmol L-1 on Day 16 (0900 hours). Mean plasma progesterone concentrations fell to less than 1.5 nmol L-1 on Day 13 (0900 hours) in ewes receiving saline and oestradiol-17 beta. Oxytocin infusion delayed luteolysis in all treated ewes; those receiving oxytocin infusion and sesame oil failed to undergo luteal regression during the period studied and in animals receiving oxytocin and oestradiol-17 beta, luteolysis was significantly delayed when compared to ewes treated with saline and oestradiol with progesterone concentrations falling to < 1.5 nmol L-1 on Days 14 (n = 1 ewe), 15 (n = 1 ewe), 16 (n = 2 ewes) and > 17 (n = 2 ewes) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299836 TI - Intracellular movements of Rickettsia conorii and R. typhi based on actin polymerization. AB - Human vascular endothelial, Vero and human embryonic lung cells infected with rickettsiae for 24 h or 48 h were labelled for polymerized actin with NBD phallacidin. Between 20 and 68% of the intracellular Rickettsia conorii had an actin tail of between 0.33 and 15 microns, with the longest tails being observed in Vero cells. In the case of R. typhi less than 1% of the organisms had actin tails and these were considerably shorter than those of R. conorii. These findings provide new information concerning the different cytopathic effects observed with the two rickettsial species. PMID- 1299837 TI - Characterization of a linear extrachromosomal DNA element (pBL1) isolated after interspecific mating between Streptomyces bambergiensis and S. lividans. AB - Streptomyces bambergiensis S712 harbours a giant linear plasmid PSB1 of 640 kb. After mating with the plasmidless S. lividans strain TK64, conjugants carrying a smaller extrachromosomal DNA element, pBL1, were identified. pBL1 is a 43-kb linear DNA molecule bound to a protein which protects it from attack by both 3'- and 5'-exonucleases. The absence of this protein drastically reduces the transforming efficiency of pBL1. pBL1 shares homology with linear plasmids and chromosomal DNA from S. bambergiensis strains. PMID- 1299838 TI - Nitrogenase activity in wheat seedlings bearing para-nodules induced by 2,4 dichlorophenoxyacetic acid (2,4-D) and inoculated with Azospirillum. AB - Nitrogenase activity (C2H2 reduction) was demonstrated in seedlings of wheat roots bearing para-nodules induced by 2,4-dichlorophenoxyacetic acid (2,4-D) and inoculated with Azospirillum brasilense. Increased nitrogenase activity was observed in inoculated para-nodulated seedlings as compared to inoculated roots not treated by 2,4-D under the conditions of assay used. 2,4-D had no stimulating effect on plant ethylene production in the absence of acetylene. When inoculation was performed with a Nif-mutant of A. brasilense, no ethylene production was detected. It was also shown that the energy source required for nitrogenase activity was supplied by the host plant. PMID- 1299839 TI - A fourth metalloprotease gene in Erwinia chrysanthemi. AB - Erwinia chrysanthemi, a Gram-negative phytopathogenic bacterium, was previously shown to secrete 3 related extracellular metalloproteases, A, B and C via a specific signal-peptide-independent pathway. A new gene (prtG) encoding a fourth, 52-kDa metalloprotease was identified on the same recombinant cosmid (pEW1) that carries the genes for the previously described proteases (prtA, prtB and prtC), for the specific secretion factors (prtD, prtE and prtF) and for a protease inhibitor (inh) cloned from E. chrysanthemi B374. The predicted sequence of PrtG was similar to those of PrtA, PrtB and PrtC, its secretion required PrtD, PrtE and PrtF; its secretion signal was located at the C terminus but its proteolytic activity was distinct from that of the 3 other proteases. Results presented here suggest that prtG could be the first gene of an operon that includes inh, prtD, prtE and prtF. PMID- 1299840 TI - Regulation of nisin biosynthesis by continuous cultures and by resting cells of Lactococcus lactis subsp. lactis. AB - Nisin production by Lactococcus lactis subsp. lactis has been investigated using lactose as carbon source. Whether or not continuous cultures were lactose limited, maximum nisin titre was observed at an intermediate mu value with a sharp peak of activity between 0.2 and 0.3/h. The maximum specific growth rate obtained in the medium used was 0.6/h and the maximum titre of nisin at mu = 0.25/h (160 AU/ml) was about nine-fold higher as compared with activity obtained at a dilution rate of 0.05/h or 0.4/h. With a constant dilution rate of 0.25/h and varying initial lactose concentrations from 3 to 40 g/l, there is an increase in nisin biosynthesis with increasing lactose concentration correlated with higher rates of sugar consumption. A Ymax value of 0.2 g bacterial dry weight and a maintenance coefficient of 124 mg lactose/g bacterial dry weight/h were determined. Lactose consumption increased from 1 to 3.28 g of lactose/g (dry wt) of cell mass/h and the nisin titre from 12.5 to 164.2 AU/ml. At higher values, nisin production declined. This implies that biosynthesis of nisin is regulated by a system of repression and derepression. Addition of lanthionine and beta methyllanthionine precursors to the medium decreased the nisin titre when either threonine, threonine-cysteine, or cysteine-serine-threonine was added at the optimal dilution rate of 0.25/h; however, simultaneous addition of serine and cysteine elicited a slight increase in nisin activity. Studies with resting cells confirm that the biosynthesis of nisin is tightly regulated, since the production rate can be 5.6-fold higher than in cells grown in continuous culture. In addition, cell-adhered nisin appears to play a role in the production of the enzyme: low levels of cell-adhered nisin elicited high production rates, whereas high levels were not associated with nisin biosynthesis. In addition to pH, magnesium sulphate and lactose concentrations, nitrogen sources were also able to interfere in cell-adherence nisin. PMID- 1299842 TI - Functional equal opportunities policy. PMID- 1299841 TI - Characteristics of cellulose colonization by a mesophilic, cellulolytic Clostridium (strain C401). AB - Using the technique of incorporation of 3H-thymidine into DNA, we describe colonization properties of an anaerobic, mesophilic, cellulolytic Clostridium, strain C401. This method took into account both bacteria which adhered and those which did not adhere to the substrate. The observed generation time (7.5 h) was faster than that detected (26 h) with other methods. Under the conditions used, the end of growth was characterized by a sharp release of biomass. A depletion in the supply of carbon source and therefore, of the adhesion site, was responsible for this release. PMID- 1299843 TI - Nursing leadership opportunities. PMID- 1299844 TI - Senior nurse managers' time. PMID- 1299846 TI - Nurse education in Poland. PMID- 1299845 TI - Time for action. PMID- 1299847 TI - Costing turnover. PMID- 1299848 TI - New horizons in community nursing. PMID- 1299849 TI - Team and primary nursing. PMID- 1299850 TI - Integrating theory and practice. PMID- 1299852 TI - Assessing needs and planning actions. PMID- 1299851 TI - Europe matters. PMID- 1299853 TI - Developing nursing theory. PMID- 1299854 TI - Managing equal opportunities in the public sector. PMID- 1299855 TI - A matter of trusts. PMID- 1299856 TI - Managing the nursing service in clinical directorates. PMID- 1299857 TI - Aiming for job satisfaction. PMID- 1299858 TI - Survival with strategic planning. PMID- 1299859 TI - Management development. PMID- 1299860 TI - Building a highly motivated team. PMID- 1299861 TI - Recognising the value of women. PMID- 1299862 TI - The concepts of theory and practice. PMID- 1299863 TI - Future conditional. PMID- 1299864 TI - Implementing Project 2000 in a context of change. PMID- 1299865 TI - The autonomy test: a guide for decision-making. PMID- 1299866 TI - The nurse and informed consent. PMID- 1299867 TI - Psychology and learning disability. PMID- 1299868 TI - Expressive objectives in psychiatric nursing. PMID- 1299869 TI - The RCN view of NHS trusts. PMID- 1299870 TI - Leaner nursing management. PMID- 1299871 TI - A study of nurse career paths. PMID- 1299873 TI - ET and modular post-registration. PMID- 1299872 TI - Stress levels in nurse education. PMID- 1299874 TI - Managing the right profile for health care. PMID- 1299875 TI - Whose interest? PMID- 1299876 TI - Modularity in occupational health courses. PMID- 1299877 TI - The management of educational change. PMID- 1299879 TI - Expectations of management. PMID- 1299878 TI - The impact of nursing models. PMID- 1299880 TI - Nurse-patient communication barriers. PMID- 1299881 TI - Perceptions of bereavement support. PMID- 1299882 TI - Patients as participants in research. PMID- 1299884 TI - Case-mix management. PMID- 1299883 TI - Psychological responses to dying and death. PMID- 1299885 TI - Nursing education strategy. PMID- 1299886 TI - Contract assignments. PMID- 1299887 TI - Labour market dynamics. PMID- 1299888 TI - Information retrieval. PMID- 1299889 TI - Diploma-level education in Norway. PMID- 1299890 TI - The ideology that underpins community care. PMID- 1299891 TI - Evaluating services for people with learning disability. PMID- 1299892 TI - Stress and its management through research. PMID- 1299893 TI - The role of the district research nurse. PMID- 1299894 TI - Living together. PMID- 1299895 TI - Computerised nursing-workload systems. PMID- 1299896 TI - Computers on the wards. PMID- 1299897 TI - Reprofiling the workforce. PMID- 1299898 TI - Skill mix in hospital. PMID- 1299899 TI - The 'conscience clause' and moral dilemmas. PMID- 1299900 TI - The impact of pay. PMID- 1299901 TI - Consumerism and participation. PMID- 1299902 TI - Does TMQ have anything to offer nurse education? PMID- 1299903 TI - Nurse teachers in Norway. PMID- 1299904 TI - Supervision--support for nurses? PMID- 1299905 TI - The knowledgeable doer. PMID- 1299906 TI - Class stereotypes. PMID- 1299907 TI - Consumer cures. PMID- 1299909 TI - Role clarity in management. PMID- 1299908 TI - Nurses and skill mix. PMID- 1299910 TI - Quality as participation. PMID- 1299911 TI - Standards for nursing management. PMID- 1299912 TI - Thinking beyond the next vacancy. PMID- 1299913 TI - Self-injurious behaviour. PMID- 1299914 TI - Nursing and Europe. PMID- 1299915 TI - Research in nursing, Part 1. PMID- 1299916 TI - Equal yet unequal. PMID- 1299918 TI - To conform or transform? PMID- 1299917 TI - The gap between nursing theory and practice. PMID- 1299919 TI - Developing courses in diabetes care. PMID- 1299920 TI - Nurses and purchasing. PMID- 1299921 TI - [Personnel training--who is responsible?]. PMID- 1299923 TI - [The design of a personal computerized database]. AB - The development of a personal data base about informatics and nursing for use on a microcomputer is presented. The advantages, effectiveness and problems involved with the construction of personal library, as well as the employed software and the references classification problems are discussed. PMID- 1299922 TI - [An outline of a conceptual framework for nursing]. AB - The taxonomy of the functions of the nurse is an attempt at the systematization of an aspect of nursing knowledge. The taxonomy consist of six classes (groups) with their corresponding categories which illustrate the performance of nurses in their field. PMID- 1299924 TI - [Iatrogenic diseases in an intensive therapy unit: a theoretical approach]. PMID- 1299925 TI - [The implementation of a program for preparing parturients for childbirth at the University Hospital of the University of Sao Paulo]. AB - The Obstetric and Neonatal Nursing Program of the School of Nursing of USP has worked with the Maternal and Infant Division of the University Hospital of USP since 1981. Among the activities carried out are the childbirth classes to prepare pregnant women, developed from 1990 as teaching-practice linkage. The evaluation of the preparation take into account the process of collaboration nursing education and nursing services. PMID- 1299926 TI - [Knowledge about AIDS among rural workers]. AB - The objective of the present study was to identify the knowledge rural workers have about AIDS in order to develop a specific educational projects. It was observed that part of the population which spontaneously participated in the study presented characteristics of misinformation and alienation about AIDS, as well as about situations that may pose risks to workers. On the basis of the responses obtained, an educational project about AIDS was elaborated to reach 1300 workers employed at a Sugar and Alcohol Mill. PMID- 1299927 TI - [Mental health nursing for women in a crisis due to accident]. AB - This study shows that the psychiatric nurse has been called to act therapeutically with hazard population in the ambit of the mental health. The author uses the technique of the aid relationship to the persons in a systematic and empathetic performance. In respect to the results obtained in intervention near the women in accidental crisis the nurse earns a real space to her mental health actions. PMID- 1299928 TI - [The nursing consultation in school health: a proposal and evaluation of an operational model]. AB - This study has the main purpose of offering some aids for a systematization of nursing attendance to the scholar and for this purpose a pattern of nursing consultation in scholars health was elaborated and evaluated by opinions of nurses (27) and students of nursing (17). The results showed its utility because the model made easy the rising of problems and needs of scholars and the performance of a nursing diagnosis and the further planning of nursing actions according to the responders. The model was considered applicable (86.4%) and some conditions were presented for its applicability. PMID- 1299929 TI - [The patient undergoing amputation of the lower limbs and the changes in activities of daily living]. AB - The present study is part of the DIOGO monograph. The objective is to verify the alterations identified in aged patients which had been submitted to amputation of their lower limbs, in relation to everyday life. The data was collected from 25 inpatients, of a government university hospital. The analysis of the results suggests that the alterations referred by the patients submitted to amputation less than 10 days before coincide with those referred by aged patients which had had their limbs amputated over a month before, in the items related to body hygiene and locomotion. PMID- 1299930 TI - [Cardiorespiratory resuscitation: the concepts and procedures in caring for adults]. PMID- 1299931 TI - [The joint hospitalization of mother and child at the Hospital das Clinicas of the State University of Campinas. The assessment of a group of mothers]. AB - This investigation is a field study involving 84 mothers who participated in the rooming-in program in the Pediatric Ward at the University Hospital of UNICAMP, Campinas Sao Paulo. The purpose of the study was to identify the mother's opinions concerning the hospitalization of their children under the rooming-in program, as well as to make a contribution towards the improvement of planned nursing care in the Pediatric Unit. Data collection was obtained through the use of a structured interview with each mother. The interview form included some mother's opinions concerning rooming-in. The results showed that these mothers considered the rooming-in program important for the treatment of the child, and that they related as "good" and "excellent" about care given in the unit. PMID- 1299932 TI - [A model of the analysis of nursing knowledge]. AB - We present an analysis based on the systemic idea where production, dissemination and utilization are constituting elements of knowledge, interdependent, allowing, in a global approach, identification of the interactions and areas of intersection. Each part, with its specific dynamism, interacts with the others, creating areas which contribute to growth. The concomitant intersection of the parts is characterized as the essence of knowledge and the dynamics of these seek the equifinality of the system: the incorporation of knowledge to practice. PMID- 1299933 TI - [The scientific production of nurses in Sao Paulo State in the triennium of 1985 1988]. AB - An exploratory study of the research carried out by nurses belonging to the Brazilian Nursing Association from 1985 to 1988 was conducted with following objectives: to analyze the characteristics of the scientific production of nurses; to identify the forms of dissemination of these studies, and to determine the expectations of nurses with respect to the Center of Nursing Studies and Research "Centro de Estudos e Pesquisas em Enfermagem" (CEPEn). Scientific papers, reports of experience, theses and monographs predominated in the production identified. The forms of dissemination most frequently mentioned were scientific events and publication in Brazilian journals. The suggestions presented to CEPEn point at the need of promoting events, courses, research meetings, research dissemination and consulting on projects. PMID- 1299934 TI - [Prospective analysis in nursing: a methodology to be disseminated]. AB - This paper intends to motivate the nurses in the evaluation of any teaching or health institutions. The authors propose the prospective analysis in nursing as a new methodological option to be used in that evaluation. The conceptual bases, as well as the methods and instruments, of the research are presented. PMID- 1299935 TI - [The Committee of Higher Education in Nursing: proposals, achievements and prospects]. PMID- 1299936 TI - [Do converting enzyme inhibitors differ from each other in the treatment of hypertension?]. AB - Novel angiotensin converting enzyme inhibitors (ACE inhibitors) have recently been commercialized and the question arises whether differences in pharmacodynamic and pharmacokinetic properties should lead to specific therapeutic choices. To our knowledge there is no data which allows the physician to conclude to any different antihypertensive efficacy when ACE inhibitors are used at adequate dosage. Their pharmacokinetic characteristics may differ at every level: absorption, distribution, metabolism and excretion. Differences in chemical structure may also influence their diffusion in various tissues, therefrom the amplitude and duration of inhibition of angiotensin II at these sites. The duration of maximum blockade of ACE and the amplitude of residual blockade may theoretically influence the duration of the hypotensive effect and the number of daily dosages. Once-daily administered long acting ACE inhibitors keep their antihypertensive action through the whole 24-hour period, during chronic treatment. The theoretical advantage of such a property is an improved control of 24-hour blood pressure. However, no study, to our knowledge, concluded to any difference between long acting ACE inhibitors as far as this parameter was concerned. In addition, except captopril which has been reported to induce major untoward effects at the time high dosages were introduced, ACE inhibitors do not seem to bear different undesirable effects. PMID- 1299937 TI - [Are non blood pressure effects of converting enzyme inhibitors important in arterial hypertension?]. AB - Lowering blood pressure by medical treatment is not enough for correct prevention of the cardiovascular complications of high blood pressure. In this respect, we would like to emphasize the potential value of the non-antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors which may be summarized as follows. In the heart, ACE inhibitors significantly reduce left ventricular hypertrophy. They have no noticeable anti-ischaemic activity and are devoid of antiarrhythmic effects. On the kidneys, ACE inhibitors seem to have a protective effect, still to be determined, in certain cases of diabetes or renal impairment. ACE inhibitors have no deleterious metabolic effects. Other antihypertensive agents share the same properties. Long-term comparative trials are necessary to find out whether some of these drugs are more effective in this field than the others. PMID- 1299938 TI - [For which hypertensive patient should angiotensin-converting enzyme inhibitor be prescribed or forbidden?]. AB - Angiotensin-converting enzyme (ACE) inhibitors act by lowering the level of angiotensin II. The therapeutic benefits of these drugs and their potential side effects therefore result from suppression of the physiological effects of angiotensin II. It is rational to prescribe an ACE inhibitor when the renin angiotensin system is activated, as in renin-dependent essential hypertension, malignant hypertension and hypertension associated with heart failure. The beneficial effects of ACE inhibitor must be weighed against the special risks of renovascular hypertension: risk of renal artery thrombosis in case of unilateral stenosis and risk of renal failure if the stenosis is bilateral or affects a solitary kidney. In some situations the renin-angiotensin system is not directly involved in hypertension but may play a local haemodynamic role, as in some cases of primary or diabetic nephropathy. In such case the ACE inhibitors are thought to exert a protective effect. ACE inhibitors were reputed to be less effective in the elderly than in younger patients, but we now know that they can be prescribed with equal success in both instances to reduce peripheral resistance and improve regional blood flow as well as arterial compliance. Finally, ACE inhibitors can be prescribed, albeit with limited effectiveness, when the renin-angiotensin system is not activated, as in low renin hypertension and idiopathic hyperaldosteronism due to adrenal hyperplasia. They are ineffective in case of Conn's adenoma and contra-indicated in pregnant women. PMID- 1299940 TI - [Converting enzyme inhibitors and aims of the objectives of the treatment of cardiac failure]. AB - Angiotensin-converting enzyme (ACE) inhibitors were introduced in the treatment of heart failure in 1982. They improve the life comfort of the patients and their capacity for exercise in both moderate and severe heart failure. In moderate heart failure, their effectiveness on exercise performance is about the same as that of digitalis compounds and classical vasodilators, and superior to that of diuretics. The superiority of ACE inhibitors lies in that they improve the prognosis of heart failure, as has been demonstrated in the severe and moderate forms of the disease and, quite recently, in asymptomatic left ventricular dysfunction following myocardial infarction. Their beneficial effects on mortality undoubtedly result from their favourable action on the neurohormonal systems which are activated early in the course of heart failure. Extending the indications of these drugs to asymptomatic patients raises questions concerning optimal dosage, date of initiation and duration of treatment and possible class effect. PMID- 1299939 TI - [Usefulness of converting enzyme inhibitors in the diagnosis of arterial hypertension]. AB - Angiotensin-converting enzyme (ACE) inhibitors are now widely used as first-line treatment of essential hypertension. Their effectiveness is potentiated by a low salt diet and, above all, by the simultaneous prescription of diuretics. When secondary hypertension is suspected, ACE inhibitors are a good pharmacological tool to study the renin-angiotensin system. Since activation of this system is the main mechanism responsible for renovascular hypertension, ACE inhibitors are very useful for diagnosis. Conversely, blood pressure is not influenced by ACE inhibitors in primary hyperaldosteronism because of the low plasma renin and angiotensin II levels. Pheochromocytoma activates the renin-angiotensin system, and ACE inhibitors combined with beta-blockers enable the hypertension to be controlled prior to surgical treatment of the tumour. Finally, ACE inhibitors can be used to explore the renin-angiotensin system in the experimental model of renovascular hypertension and therefore contribute to our knowledge of the complex pathophysiology of this most frequent type of secondary hypertension. PMID- 1299941 TI - [Management of the treatment with converting enzyme inhibitors in chronic heart failure]. AB - Treatment with angiotensin-converting enzyme (ACE) inhibitors can begin at any time when a left ventricular dysfunction has been diagnosed. In the absence of rare contra-indications (renal artery stenosis, connective tissue disease, severe renal failure), all patients with asymptomatic or, a fortiori, symptomatic chronic heart failure can benefit from ACE inhibitors, whatever the origin of the heart failure. Among the ACE inhibitors now available, the benefits of captopril (3 daily doses) and of enalapril (2 daily doses) on all the targets of cardiac failure treatment are now well established. The effects of lisinopril on mortality are not yet known, but the haemodynamic and symptomatic benefits of this drug are also well established (with the advantage of once daily administration). Other ACE inhibitors with less numerous and less convincing trial reports can be used or rejected depending on the physician's faith in the effects of this pharmaceutical class. With all ACE inhibitors the initial dose must be very low, to be gradually increased over several days or even weeks until the highest dose tolerated is reached. ACE inhibitors can be associated with the classical treatment of cardiac failure. A previous diuretic treatment with sodium depletion may increase the risks of first dose effect and renal intolerance due to the introduction of the ACE inhibitors. Theoretically, the combination of ACE inhibitors and spironolactone is to be avoided for fear of hyperkalaemia and renal deterioration. Yet, provided some precautions are taken this combination may improve the benefits of ACE inhibition when the renin-angiotensin-aldosterone system inhibition is not optimal. However, this has yet to be demonstrated by prospective clinical trials. PMID- 1299942 TI - [Converting enzyme inhibitors and coronary failure]. AB - Nearly 15 years ago, it has been shown that myocardial infarction is accompanied by left ventricular dilatation. In the following years more details were obtained on morphological changes consecutive to myocardial infarction, now grouped together under the term left ventricular remodelling. These changes enable the patients to survive despite reduction of the contractile ventricular mass, but they expose the ventricles to constraints resulting in excessive work load. It has been shown that these changes can be reduced by early myocardial reperfusion and by administration of angiotensin-converting enzyme (ACE) inhibitors. These findings were established first in animals, then in man. Administering ACE inhibitors to patients with symptomatic heart failure consecutive to advanced ischaemic cardiopathy prolongs the patients' survival. When ACE inhibitors are given to patients with severe asymptomatic left ventricular dysfunction which started soon or long after a myocardial infarction, they reduce the frequency of ischaemic events, passage to symptomatic heart failure and, at least in one study, mortality. ACE inhibitors have also been shown to reduce the size of myocardial necrosis when administered in the acute phase of experimental myocardial infarction. Preliminary data have demonstrated that ACE inhibitors given in the acute phase of myocardial infarction reduce the left ventricular dilatation which follows infarction. However, a study of ACE inhibitors administered to a large number of patients in the acute phase of myocardial infarction had to be interrupted because of the over-mortality in the treated group. These facts are reviewed in this article, and attempts have been made at deducing from them the current indications of ACE inhibitors in patients with coronary heart disease. PMID- 1299943 TI - [Converting enzyme inhibitors in diabetes]. AB - ACE inhibitors are used on a large scale basis in hypertensive diabetics, while the association between diabetes and hypertension is frequent and harmful. This is due to their excellent tolerance and efficacity. No specific advantage has been reported in their use regarding tolerance, i.e., they may not alter insulin sensitivity consistently. Conversely, ACE inhibitors may offer the specific advantage of protecting kidney function against diabetic microangiopathy, since their effects on glomerular haemodynamics seem independent from their hypotensive effect. PMID- 1299944 TI - [Short treatments of tuberculosis. A choice without compromise with therapeutical efficacy and the incidence of relapses]. PMID- 1299945 TI - [Fibrinolytic agents in cerebral ischemic accidents. A hope more reserved than in myocardial infarction]. PMID- 1299946 TI - [Analgesia controlled by the patient. A progress in the treatment of postoperative pain]. PMID- 1299947 TI - [Pulmonary pathology of drug origin]. AB - Over the past ten years, there has been an impressively growing number of reports about drug-induced pneumonitis (DIP) due to more than one hundred different drugs. The most troublesome question is how to establish with certainty the diagnosis. Usually, five criteria are necessary. 1) The administration of a drug on a more or less long term basis. 2) Newly occurrence of an interstitial pneumonitis (defined on symptomatology, radiological features, pulmonary function test results). 3) Elimination of all other causes of pneumonitis (haemodynamic, infectious, systemic, environmental diseases). 4) Broncho-alveolar lavage (BAL) cell data showing in most cases a lymphocyte alveolitis with an inverted CD4/CD8 ratio. In a certain number of ambiguous circumstances, coupling a provocation test with a sequentially performed BAL could firmly establish the diagnosis. 5) Rapid resolution within a few days or months of the pneumonitis as early as the incriminated drug administration is stopped. Nevertheless sometimes one or more of these criteria are not met, mainly when the pneumonitis is a fibrosis directly induced by a fibrosing toxic mechanism. PMID- 1299948 TI - [The fiftieth anniversary of the discovery of hypoglycemic sulfonamides]. PMID- 1299949 TI - [Fractures of the distal end of the radius in adults. Mechanism, diagnosis, treatment]. PMID- 1299950 TI - [Corticosteroids: topical cutaneous. Principles and rules of use, posology]. PMID- 1299951 TI - [Cancer of the uterine cervix. Epidemiology, pathological anatomy, screening, diagnosis, development, prognosis, treatment]. PMID- 1299952 TI - [Lower urinary tract infections. Epidemiology, etiology, physiopathology, diagnosis, development, treatment]. PMID- 1299953 TI - [Chronic duodenal ulcer. Epidemiology, physiopathology, diagnosis, development, treatment]. PMID- 1299954 TI - [Conjugated bilirubin jaundice in adults. Diagnostic orientation]. PMID- 1299955 TI - [Tremor. Diagnostic orientation]. PMID- 1299956 TI - [Feto-maternal blood immunization. Screening, prevention]. PMID- 1299957 TI - [Nutritional requirements in infants, in children and in pregnant and breast feeding women. Energy, iron, proteins, essential fatty acids, vitamin D, calcium]. PMID- 1299958 TI - [Amplification and desensitization in platelet activation]. PMID- 1299959 TI - [Roles of substantia nigra and piriform cortex in epilepsy attacks and anti epilepsy]. PMID- 1299960 TI - [Advances in the origin, effect and regulation of inhibin]. PMID- 1299961 TI - [Vasopressin receptors, antagonists and cardiovascular regulation]. PMID- 1299962 TI - [Embryonic-origin interferons and maternal recognition of pregnancy]. PMID- 1299964 TI - [Evaluation of combined drug action]. PMID- 1299963 TI - [Renin-angiotension system in gonad and uterus]. PMID- 1299965 TI - [Effects of thymus gland and sex hormones on the activity of hepatic drug metabolic enzymes and the regulation of anti-oxidation function]. PMID- 1299966 TI - [A novel hormone in islet of pancreas--islet amyloid polypeptide]. PMID- 1299967 TI - [Progress in the study of A channel]. PMID- 1299968 TI - [Leukocyte adherence to endothelial cell and its significance]. PMID- 1299969 TI - [Immune physiology and biochemistry of complement 3b receptors on erythrocytes]. PMID- 1299970 TI - [Atrial natriuretic polypeptide and blood-brain barrier]. PMID- 1299971 TI - [From antiarrhythmic effects to pro-arrhythmic effects]. PMID- 1299972 TI - [Pro-arrhythmic effects of anti-arrhythmic agents. Study methods and difficulties in analysis]. PMID- 1299973 TI - [Torsades de pointes and anti-infective agents]. PMID- 1299976 TI - [Economic impact of adverse drug effects. Some reflections]. AB - The cost of adverse drug effects first began to be analyzed in the 1960s, with an evaluation of related admissions to hospital in the USA. The average cost per patient of adverse events requiring hospitalization in France was estimated at 6,250 F in neurology units in 1979/1980, and 14,920 F in geriatric units in 1984. Fifty per cent of these events were avoidable. A second approach is to measure the cost of certain iatrogenic manifestations, e.g. fever due to fipexide, stenosis and perforation of the small intestine due to potassium chloride, gastrointestinal bleeding due to NSAIDs, kidney damage due to aminosides, etc. Calculations of the economic impact of adverse drug effects must also take into account indirect costs such as loss of productivity. The lack of such studies should not make health care specialists forget the magnitude of the problem. PMID- 1299975 TI - [Antidepressants and cardiac side effects. Evaluation trial]. AB - When a new antidepressant is put on the market, everyone is afraid of its possible cardiac effect. The control of unicellular potentials can give an hint about that effect, without being able to assess its severity; the 27 antidepressants commercialized in France have been reviewed. 180 cases of conduction delays from 10,060 overdosage in the Paris poison center were found, 7 times more often than with other drugs. In addition the 30 centers for monitoring of side effects of drugs have collected 38 cardiac side effects, as well arrhythmias or conduction disturbances. PMID- 1299974 TI - [Multicenter prospective study of cardiac accidents during treatments with 5-FU]. AB - In a prospective, multicenter study, we evaluated the incidence of adverse cardiac effects in 1097 patients receiving 5-FU as a short i.v. perfusion or as a continuous perfusion over 3 to 5 days. There were 29 cardiac events (incidence 1.6%; 4.5% in patients with a history of cardiovascular disease, 1.1% in the remainder). Adverse effects were more frequent in the patients with advanced WHO (WHO = OMS) stage (2 or 3) primary tumors of the upper respiratory or digestive tract, or of the gastrointestinal tract, when 5-FU was given as a continuous perfusion. They also appeared to be more frequent in patients with a history of cardiovascular disease, and mainly occurred during the second or third day of the first course of treatment. Retreatment of eight patients with 5-FU led to the recurrence of symptoms in five. The outcome of these adverse cardiac effects was generally favorable, but 11.5% of the patients died. PMID- 1299978 TI - [Pulmonary toxicity of nilutamide (Anandron). Cooperative evaluation of French Regional Pharmacovigilance Centers]. AB - We have studied 12 reports of pneumonitis associated with nilutamide (Anandron) and notified to the French regional ADR monitoring centers between November 1987 and June 1990. The mean age of the patients was 71.5 +/- 9.5 years, and 35% (5/12) had a history of lung disease. All 12 patients developed dyspnea, cough and fever, 4.7 +/- 6 months after starting nilutamide. Ten patients (83%) required admission to hospital. The symptoms revolved in 11 cases when the drug was withdrawn. In the other case, they disappeared when another drug was stopped and the dose of nilutamide was reduced. Six patients were treated with glucocorticoids. The severity of nilutamide-associated pneumonitis appears to be related to the time between the onset of dyspnea and consultation. PMID- 1299977 TI - [Adverse effects of oxybutynin chloride (Ditropan). Evaluation of the official survey of Regional Pharmacovigilance Centers]. AB - We analyzed the 200 reported cases of adverse reactions to Ditropan (209 side effects) collated by the Centres Regionaux de Pharmacovigilance and Laboratoire Debat since the drug was first marketed. The frequency of such side-effects was of the order of 1 per 20,917 treatment months. Children were affected four times more frequently than adults. The manifestations resembled atropine overdose in 103 cases (52 children, 51 adults), and were mainly neurological (59%) and ocular (22%). Two cases of erythema multiform and 33 of miscellaneous allergic skin reactions occurred. The fact that atropine overdose was more frequent in children can be explained by the proportionately higher dosage. Dose adjustment based on pediatric pharmacokinetic studies appears to be essential. In children, the drug is prescribed most frequently (56%) for conditions outside the licensed indications, particularly nocturnal enuresis, a condition for which the efficacy of Ditropan has not been established. We consider that this calls for a specific contraindication in isolated nocturnal enuresis and in children aged less than five years. PMID- 1299979 TI - [Drug-induced aseptic meningitis]. AB - Aseptic meningitis is a very rare drug reaction involving non-steroidal antiinflammatory agents (ibuprofen and sulindac), antibiotics (cotrimoxazole, trimethoprim, ciprofloxacin) and miscellaneous drugs such as carbamazepine, human immune globulin and muromonab CD3. Meningeal symptoms occur a few hours after drug intake and resolve without sequelae within one or two days after drug withdrawal, mainly in young females with systemic lupus erythematosus or mixed connective tissue disease. Biological findings and radiological investigations are not suggestive of an infectious etiology or rheumatological/neurological disturbances. Diagnosis is simple when recurrent episodes coincide with drug ingestion. PMID- 1299980 TI - [Drug-induced benign intracranial hypertension. Apropos of a case with amphotericin B. Review of the literature]. AB - Benign intracranial hypertension (BICH) is a rare adverse event. We report the case of a 31-year-old female drug addict who had been seropositive for HIV since 1987. She had stage IV C1 AIDS, and was receiving intravenous amphotericin B for generalized cryptococcosis with no neuromeningeal involvement. She developed BICH that regressed when the antifungal drug was withdrawn and treatment for cerebral edema was started. BICH is a clinical entity involving intracranial hypertension with no focal neurological signs or detectable intracranial lesion. The manifestations include headache, transitory or permanent visual disturbances (diplopia, loss of visual acuity) and the perception of intracranial noise. The cerebrospinal fluid is under increased pressure but the composition is normal. The eye fundus examination shows papillary edema, and the neuroradiological workup is normal. BICH can only be diagnosed once an expansive intracranial process, neuromeningeal infection, and non-communicative hydrocephalus have been ruled out. In the majority of cases, no etiology is found. Such cases of idiopathic BICH usually occur in overweight young women, although drugs can be implicated. Amphotericin B has not previously been held responsible for BICH. On the basis of this observation, we present a review of the literature. PMID- 1299981 TI - [Neurologic side effects of fluoroquinolones. Apropos of 9 cases concerning pefloxacin]. AB - Neurological side-effects were a limiting factor with older quinolones. Although they appear to be less frequent with the newer fluoroquinolones, we observed nine such cases at Amiens University Hospital over a four-year period. The patients were six women and three men, with a mean age of 61 years. They received a mean dose of 800 mg/day of pefloxacin. Four had septic shock, one left ventricular failure, and seven had signs of cholestasis (signs of liver failure were absent). Neurological manifestations occurred between 24 hours and seven days after starting treatment and disappeared within 24 to 48 hours of stopping the drug or reducing the dosage. They included myoclonia (3 cases), convulsions (2 cases, one with concomitant theophylline), delirium and agitation (2 cases, one in a patient on steroids) and confusion (3 cases). Plasma drug levels were determined in six patients and were above normal peak levels (10 micrograms/ml) in five. Pefloxacin was measured in the cerebrospinal fluid in two cases (8.7 and 15.0 micrograms/ml). Neurological manifestations during pefloxacin treatment are probably related to overdose (plasma levels were above normal in 5/6 cases), possibly being favoured by cholestasis (7/9 cases) and/or hemodynamic factors (5/9). Symptoms can resolve when the pefloxacin dosage is reduced. PMID- 1299982 TI - [Thrombopenia due to pefloxacin (Peflacine): dose-dependent toxicity?]. AB - Pefloxacin (Peflacine) can give rise to thrombocytopenia, although the responsibility of the drug can be difficult to demonstrate in infectious patients and those receiving other drugs simultaneously. We have collated 18 cases in which the responsibility of pefloxacin was suspected. In 13 cases, the patients were also taking other drugs which may have been contributory (heparin, Bactrim, Augmentin, ranitidine,...). The remaining five cases were of particular interest as pefloxacin was the only drug administered. The mean age of the patients was 75 years, and the mean bodyweight 56 kg (range, 47-65 kg). The pefloxacin dosage was 800 to 1,600 mg/day i.v. or p.o., i.e. 13-18 mg/kg/day. Thrombocytopenia occurred from five to 19 days after beginning treatment and resolved between 7 and 12 days after drug withdrawal. A number of factors argue in favor of dose dependency: 1 patient had high plasma concentrations (peak and residual); thrombocytopenia occurred in one patient when the previous, well-tolerated dosage of 800 mg/day (for 15 days) was increased to 1,600 mg/day; thrombocytopenia resolved in one patient when the dosage was reduced to 400 mg/day (1 tablet) and continued for a further 10 days. This toxic reaction may be avoided by reducing the drug dosage to 400 mg/day in elderly patients with a low bodyweight. Differential blood counts appear to be warranted for patients at risk. PMID- 1299983 TI - [Evaluation of the activities and value of allergo-anesthetic consultation at the University Hospital Center of Nice 1985-1991]. AB - Life-threatening accident during anesthesia scarcely happen but the consequences may be dramatic. We report our experience of an allergo-anesthesia consultation created since 1985 in Nice hospital. 452 patients have been investigated: 1) 109 for life-threatening anaphylactic and anaphylactoid drug reactions. They have been investigated by: skin tests intradermal reactions (IDR) and prick tests with substances used during anesthesia (drugs and latex) and for all the muscle relaxants; the radioabsorbent test (RAST) for the muscles relaxants, propofol and latex; the human basophilic degranulation test (HBDT) for all the other drugs. We used the imputability decision table to classify the reactions. When anaphylaxis diagnosis was established (14) an "allergy card" was given to patients which identified the drugs to which they had a positive reaction. 62 patients have presented an anaphylaxis: 57 due to muscle relaxants (37 due to suxamethonium), 4 to latex and 1 to a gelatin. Patients were subsequently contacted and 50 of the 58 have responded. 18 of these patients have received 22 new anesthesias. Without exception, the advises to avoid a drug have been followed, 17 patients have a positive reaction to a muscle relaxant. In four of these, another muscle relaxant (skin test negative) was used without any trouble. For the other 13 who had shown a cross reactivity, all the muscle relaxants had been rejected and another anesthetic technique have been used: local anesthesia (3 cases), epidural (2 cases) associated or not with narcotics (propofol, midazolam), general anesthesia (propofol, midazolam, droperidol, phenoperidine). These drugs were all skin test negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1299984 TI - [Role of pharmacovigilance center in information for the public on drugs. Experience in Marseille on 9 month]. AB - We analyzed the role of the Marseille pharmacovigilance center (working in collaboration with the local poison treatment center) in informing the general public on medicinal drugs. Over a 9-month period, the center received 115 requests from members of the public for information. 82.6% of callers were not members of the health professions and wanted information for themselves (61.7%, 67.6% women) or their children (26.08%). The questions mainly involved drug interactions (28.7%), side-effects (26%) and precautions for use in particular circumstances (20%). 178 proprietary drugs (47 of which had been bought over the counter) were mentioned. The main therapeutic classes were neuropsychiatric drugs (n = 41), cardiovascular drugs (n = 17) and analgesics (n = 16). A number of communication difficulties and problems of a deontological nature were encountered. Full information was provided in every case, together with advice on prevention to about half the callers. PMID- 1299985 TI - [Desmopressin: hyponatremia and convulsions]. PMID- 1299986 TI - [Hyperlactacidemia in bronchodilator treatment with salbutamol and theophylline in a premature infant]. PMID- 1299987 TI - [Evaluation of survey on drug distribution in two social assistance establishments for the elderly]. PMID- 1299988 TI - [Peripheral facial paralysis following vaccination against hepatitis B. Apropos of a case]. PMID- 1299989 TI - [Distal subacute ischemia of left lower limb during treatment with a combination of dexfenfluramine and minocycline]. PMID- 1299990 TI - [Pseudohyperaldosteronism by chronic overdose of "Pulmoll" expectorant lozenges]. PMID- 1299991 TI - [Anaphylactic shock induced by flumequine]. PMID- 1299992 TI - [Lyell syndrome or toxic epidermal necrolysis and Stevens-Johnson syndrome after treatment with fluoxetine]. PMID- 1299993 TI - [Fatal accident caused by quinidine in the preventive treatment of atrial fibrillation relapse]. PMID- 1299994 TI - [Acute rhabdomyolysis during treatment with simvastatin (Zocor)]. PMID- 1299996 TI - [Acute rhabdomyolysis and meprobamate poisoning]. PMID- 1299995 TI - [Acute rhabdomyolysis due to fenoverine (Spasmopriv). A case and review of the literature]. PMID- 1299997 TI - [Antiparkinsonian drug consumption in a University Hospital Center 1981-1990]. PMID- 1299998 TI - [Role of adverse effects of immuno-allergic nature at a Regional Pharmacovigilance Center]. PMID- 1299999 TI - [Hypoglycemic coma in a patient treated with glipizide and fluconazole: a possible interaction?]. PMID- 1300000 TI - [Progression of psoriasis under the effect of a timolol-containing ophthalmic solution]. PMID- 1300001 TI - [Comparative study of data banks on drug interactions]. AB - Authors have listed 9 criteria for testing scientific quality of computerized drug-interactions data banks. Pair of drugs with or without interactions, have been selected for each of these criteria and have been used for interrogation of eight data banks. None of these are completely satisfactory but errors or omissions are more or less important. PMID- 1300002 TI - [Renal artery aneurysms in children]. AB - Renal artery aneurysms were diagnosed in 11 patients (9 boys) aged 1 to 14. The examinations were carried out for vasorenal hypertension in 4 cases, for bladder ureter reflux, hematuria, nephroptosis in 4, ureterohydronephrosis in 2 cases, and for interstitial nephritis. Aneurysms of the major trunk of the renal artery, mostly oval-shaped, 11 x 14 to 25 x 28 mm in size, were detected in 4 patients, intrarenal aneurysms 2 x 3 to 5 x 6 mm in size in 7 cases. The share of aneurysms among uronephrologic conditions in children was found to be 1.54%, among vasorenal hypertension cases, 4.3%. Vasorenal hypertension is the main optional sign of aneurysms of the main trunk of the renal artery, whereas for intrarenal aneurysms such sign is hematuria. PMID- 1300003 TI - [The shape of the thorax based on data of fluorographic studies]. AB - Five thoracic types were distinguished on the basis of 3 transverse sizes between the 4th, 7th, and 10th ribs, detected on the thoracic fluorograms of 1116 men and 1460 women: cylindrical, narrow conical, conical, wide conical, and egg-shaped. A subtype of a cylindrical thorax--cylindrical with a waist--was distinguished in women. In men conical chests occurred in 48.9% of cases, wide conical in 24%, whereas in women narrow conical chests occurred in 41.8% and cylindrical in 27.5% of cases. The examinees were grouped in accordance with the thoracic shape and their physical parameters and the parameters of the chests were compared. The chest proportions represent the most comprehensive characterization of the skeletal index: the ratio between the transverse size between the 7th ribs and the vertical size in per cent. The skeletal index directly correlates with body mass, thoracic circumference, transverse and longitudinal sizes of the heart and is in inverse correlation with body length, angle of inclination of the 8th rib and angle of inclination of the heart axis to the horizontal line. PMID- 1300004 TI - [Algorithms of x-ray and ultrasonic diagnoses in urology]. AB - Roentgenourologic methods and ultrasonic scanning (USS) should be combined in the radiologic diagnosis of urologic diseases. USS should be the first stage of examinations of urologic patients, and its results should be taken into account when planning and carrying out excretory urography. USS can be repeated before more sophisticated roentgenourologic examinations in order to single out the "zones of interest"; special programmes are possible for the purpose pharmacoechography, dopplerography, etc. Development of tentative algorithms of x ray and ultrasonic diagnosis of the major urologic diseases will help optimize the diagnostic process. PMID- 1300005 TI - [The use of Doppler ultrasound of the renal arteries for the diagnosis of vasorenal hypertension at the outpatient stage]. AB - Ultrasonic dopplerography of the renal arteries was used to improve the differential diagnosis of arterial hypertension before hospitalization. Dopplerograms of the renal arteries of normal subjects were characterized by almost symmetrical parameters of the blood stream. In patients with vasorenal hypertension a marked asymmetry of the blood stream was seen with its reduction and qualitative changes in the dopplerogram on the side of the stenosed renal artery, that was confirmed by angiographic findings. Chronic pyelonephritis was dopplerographically characterized by hemodynamically insignificant asymmetry of the blood stream in the renal arteries with its reduction on the side of the involved kidney. In essential hypertension the type of asymmetry of blood stream parameters in the renal artery seemed similar to that in normal subjects. PMID- 1300006 TI - [Structural changes in the brain according to computed tomographic data in patients undergoing combination therapy for hemispheric gliomas]. AB - Basing on CT data, the authors analyze the qualitative changes in the brain of patients with a history of multiple-modality treatment for immature neuroectodermal tumors. Plani- and volumetric parameters of the total brain, the involved and the contralateral hemispheres are compared with the same parameters in the reference group. The pattern and degree of structural changes were found related to the site of the tumor and surgery. The brain matter in both hemispheres was lost mostly in the interstitial and end portions predominantly on the side of the tumor and surgery. Changes of the brain were individual in the patients. PMID- 1300007 TI - [X-ray endovascular surgery of the right ovarian vein syndrome]. AB - The author analyzes the causes of the disorders in the urodynamics and retention changes in the upper urinary routes of 43 infertile women who suffered from disordered venous reno-ovarian circulation. In chronic phlebostasis of the pelvic organs a compensatory varicose dilatation of the right ovarian vein, mediating the hemodynamic decompression of the venous bed of internal genitals, is responsible for the development of the venous compression syndrome of the right ureter. To correct the vasourethral conflict roentgenoendovascular embolization of the left ovarian vein was carried out. In the remote postembolization period 40 women presented without pain or urodynamic disorders and with normal urinalyses, in 3 women the right ureter dilatation persisted but had not progressed. PMID- 1300008 TI - [X-ray semeiotics of cranial involvement in endocrine diseases]. AB - The incidence and type of x-ray semeiotics of the skull involvement were studied in 703 patients with endocrine diseases (26 with acromegaly, 36 with hypercorticism, 104 with thyrotoxicosis, 23 with hypothyrosis, 98 with primary hyperparathyrosis, 302 with diabetes mellitus, 114 with hypogonadism). Craniogram analysis involved study of the thickness and structure of the vault bones, shape and size of the skull, status of the sutures, internal plate relief, changes of the base of the skull, of the sella turcica first of all, and facial bones. The characteristic x-ray symptom complexes of the involvement of the skull in some endocrine diseases were distinguished. PMID- 1300009 TI - [Potentialities of transcutaneous and transhepatic cholangiography as a method of studying diseases of the bile excretory system]. AB - Comprehensive examinations of 62 patients with jaundice of obscure origins involved transcutaneous transhepatic cholangiography carried out in all the patients, hepatolymphography in 60 cases, relaxation duodenography in 31, angiography in 41, ultrasonic examination of the liver in 31, endoscopic retrograde pancreatocholangiography in 28 and liver scanning in 19 patients. These studies have extended the knowledge on the biliferous system status in obturation and parenchymatous jaundices and helped define the role of transcutaneous transhepatic cholangiography among the invasive methods of radiologic examinations and pararadiologic methods. PMID- 1300010 TI - [The role of computed tomography in the diagnosis of brain involvement in patients with posttraumatic epilepsy]. AB - Fifteen patients with posttraumatic epilepsy (10 men and 5 women aged 15 to 47) were examined in 1990-1991. All the patients had a history of craniocerebral injury (closed in 7 and open in 8 cases), 6 of them were operated on for intracranial hematomas. Besides CAT, electroencephalography, craniography, and examination of the fundus oculi were carried out. CAT was performed with a Ct MAX (General Electric) unit. Standard positioning of the patients with sectional projections parallel to the orbital meatal line was used. Changes in the brain matter were detected in 13 of these 15 patients: foreign bodies (2 cases), meningeal cerebral cicatrices (5), dilatation of the ventricular system (4), petrificates in the brain matter (1), atrophic changes of the cerebral cortex (1). The tomograms of two patients were normal. Ten patients were operated on: 2 were subjected to anterior callosotomy, in 2 foreign bodies were removed, and in 6 patients staged plasty with removal of the meningeal cerebral cicatrix was carried out. The detected CAT changes helped diagnose the topical location of the epileptogenic focus and choose the optimal method of surgery for posttraumatic epilepsy. PMID- 1300011 TI - [A comparative evaluation of the clinical x-ray picture of uremic osteodystrophy before and after parathyroidectomy]. AB - The authors present the results of clinical, x-ray, and biochemical studies carried out in 51 patients with uremic osteodystrophy, treated with hemodialysis, before and after parathyroidectomy. The patients were divided into 4 groups with various patterns of x-ray symptoms. Patients with x-ray signs of fibrous osteodystrophy made up group 1, the second group consisted of patients with a combination of fibrous osteodystrophy and osteomalacia with secondary hyperparathyrosis predominance; the third group, like the second one, included patients with the mixed form of uremic osteodystrophy, but with the predominance of the osteomalacic syndrome; Group 4 patients had no x-ray signs of bone changes, and the diagnosis of uremic osteodystrophy was confirmed by clinical laboratory evidence. Analysis of the clinical and x-ray data before and after parathyroidectomy has brought the authors to a conclusion that such an intervention was effective only in cases with manifest clinical and x-ray symptoms of fibrous osteodystrophy. In Group 2 patients with the mixed form of uremic osteodystrophy and less manifest osteomalacia as against fibrous osteodystrophy, subtotal or partial parathyroidectomy is advisable only in cases when conservative therapy is of no avail and fibrous dystrophy is progressing. Surgical treatment is contraindicated to patients in whom x-ray signs of osteomalacia predominate over fibrous osteodystrophy in the total picture of uremic osteodystrophy; it may result in a rapid progress of osteomalacia. PMID- 1300012 TI - [Echotomography and excretory urography in the diagnosis of renal parenchymal "bridges"]. AB - Sonographically detectable parenchymal 'bridges' in the median segment of the kidney may look atypical. The most incident parenchymal 'bridges' are asymmetric irregular ovoid incomplete connections, not reaching the parenchyma at the site of renal hilus; such 'bridges' may be compared to a 'humpbacked' overturned kidney. Besides that, double and Y-shaped connections were detected, occurring in different variants of fused kidneys. Clinical significance of atypical 'bridges' of the parenchyma consists in simulation by them of echomixed processes, of renal tumors first of all. Excretory urography should be the second stage of the diagnosis after initial ultrasonic examination of the kidneys; after it repeated pointed ultrasonography should be carried out, that will help rule out the diagnosis of a renal tumor. PMID- 1300013 TI - [A study of regional ventilation of the lungs in patients with chronic bronchitis using scanning densitometry tomograms]. AB - A new method for examination of regional ventilation of the lungs has been developed, that permits assessment of the ventilation in patients with chronic bronchitis and detect a latent respiratory insufficiency. The results of examinations with this method conform to the results of examinations of external respiration function. PMID- 1300014 TI - [Diagnostic capabilities of the x-ray endoscopic method of study in cholelithiasis]. AB - The developed variants of the roentgenoendoscopic method for the examination of the pancreatobiliary system were employed in 256 patients with various diseases of the gallbladder and biliary duct. The results of application of these methods in 85 patients with cholelithiasis are presented. Different potentialities of the roentgenoendoscopic method and ultrasonic scanning for the assessment of the biliary system status in cholelithiasis were revealed. The findings recommend supplementing ultrasonic examinations with an optimal variant of the roentgenoendoscopic examination. PMID- 1300015 TI - [The characteristics of the interaction of glycogenolytic enzymes with glycogen in endothermic and ectothermic animals]. AB - It has been shown that the dependence of glycogenphosphorylase kinase activity on the quantity of glycogen added corresponds to the glycogenphosphorylase saturation curve by glycogen obtained during investigation of complex formation with the muscle glycogenphosphorylase of the animals: rat, frog Rana temporaria and fish Raja clavata under identical conditions. We suggest that glycogenolytic enzymes organize regular structure on glycogen particle. Glycogenphosphorylases of heat-loving animals have high affinity to glycogen that is accounted for necessity to keep the structure in natural conditions. PMID- 1300016 TI - [The dependence of the rate of heart contractions in the long-tailed Yakutsk suslik Citellus undulatus on environmental temperature]. AB - Decrease of ambient temperature (Ta) leads to the increase of the heart rate (HR) in active ground squirrels C. undulatus by 5.3/min/1 degree C in summer and by 3.8/min/1 degree C in winter. In a hibernation state, the dependence of the HR on Ta was in a good agreement with equation HT = 2.53.exp.(0.1.Ta). On entering into hibernation and on arousal, the HR change outruns the corresponding body temperature (Tb) change by 1.5-2 hours. A maximum HR level (up to 400/min and more) was registered on arousal when Tb reached 17-20 degrees C. A minimal HR level (4-5/min) was observed during hibernation at Ta 2-5 degrees C. The maximum Ta, at witch C. undulatus was hibernating, reached 23-24 degrees C, the HR being 23-25/min. PMID- 1300017 TI - [The temporal organization of human fetal motor function]. AB - Fetal motor bursts were recorded in pregnant women at 11-18, 20-24 and 30-32 weeks of pregnancy. It was stated that spontaneous motor activity in human fetus is similar to autogenic periodic motor excitation observed in other species of vertebrates, i.e. presence of the main rest-activity circles with a period near 1 minute, the existence of rhythmic components with 6-8-second intervals during active phases and decreasing of quantity of excitation bursts with age. PMID- 1300018 TI - [The effect of vasotocin, mesotocin and adrenaline on the interrenal gland in the frog Rana temporaria under in-vitro conditions]. AB - Morphometric studies indicate that vasotocin increases the activity of the adrenal gland in frogs, whereas mesotocin and epinephrine do not essentially affect it. Combination of epinephrine with nonapeptides in cultural medium showed that the former may abolish the effect of vasotocin on the adrenal gland. PMID- 1300019 TI - [The general features in the evolution of the functions of homeostatic and informational systems]. PMID- 1300020 TI - [The role of resonance phenomena in motion sickness]. PMID- 1300021 TI - [The characteristics of the intragroup behavior of rhesus macaques and hamadryas baboons during the realization of food motivation in a competitive situation]. AB - The aim of the present work is to consider the specific interrelations in "family" units of macaques (Macaca mulatta) and baboons (Papio hamadryas) during food-getting reactions in competitive conditions. Detailed analysis of dyadic interactions revealed that competing partners demonstrate more various types of behaviour tactics at the initial stage of learning. At the final one, only males of both investigated species performed instrumental reactions and received the food reward. All females demonstrated much more vocal reactions in comparison with males. Thus the variety of competing interactions between heterosexual partners, learning and possibility to realize its motivation correspond ro novelty of experimental situation and degree of intraspecies social subordination. PMID- 1300022 TI - [Study on the toxicity and antitumor activity of adriamycin-DNA and amsacrine-DNA complexes in mice]. AB - We have compared in vitro binding of adriamycin (ADR) and amsacrine (AMSA) with DNA, the toxicity, and the antitumor activity of ADR-DNA and AMSA-DNA, after intraperitoneal (ip) injection in mice. The binding of ADR with DNA is 100-fold higher than that of AMSA with DNA. The overall toxicity of ADR-DNA is significantly lower than that of ADR. ADR-DNA is more effective than ADR against three models of S180 sarcoma (by sc, ip and i.v. inoculation into mice). The peak levels of ADR-DNA and ADR were 265 +/- 24 ng.ml-1 versus 108 +/- 16 ng.ml-1 (P < 0.01). AUC 0-12 h were 1064 +/- 84 ng.h-1 x ml-1 versus 382 +/- 27 ng.h-1 x ml-1 (P < 0.01). The levels of ADR in most of tissues and tumor after administration of ADR-DNA were higher than those after administration of ADR. Moreover, there is no difference in toxicity, therapeutic effects as well as AUC between AMSA-DNA and AMSA. PMID- 1300023 TI - [Protective effects of cyproheptadine on calcium paradox in isolated rat hearts]. AB - The protective effects of cyproheptadine, an antiserotonin-antihistaminic agent with calcium channel blocker activity, on calcium paradox in isolated Langendorff's heart in rats were studied. After a 5 min of calcium-free perfusion [standard Krebs-Henseleit (K-H) buffer without calcium, gassed with 95% O2 and 5% CO2] followed by a 20 min of normal K-H buffer (Ca2+ 2.5 mmol/L) perfusion, extensive and rapid myocardial injury was observed: release of massive cellular enzymes such as lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), significant decrease of myocardial anti-oxygen free radical enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities but no obvious change of myocardial lipid peroxides such as malondialdehyde (MDA) content was observed. The loss of normal colour and mechanical activity, even contracture, was also observed in the injured hearts. Cyproheptadine (2.5-5 mumol/L) was shown to effectively antagonize the damage. The results suggest that the protective effects of cyproheptadine on the calcium paradox may be related to its actions of blocking calcium channel, protecting anti-oxygen free radical enzymes and scavenging oxygen free radicals in the myocardial tissues. PMID- 1300024 TI - [Proliferation of lymphocytes T and B by prehispanolone LC-5504 of Leonurus hereterophyllus Sweet]. AB - Leonurus hereterophyllus Sweet is a traditional Chinese herbal medicine used to treat menstrual disturbances in woman. A new labdane diterpene, prehispanolone LC 5504, namely 9 alpha, 13R,15,16-diepoxy-labdane-14-en-7-one, had been isolated. The authors studied the synergism of labdane diterpene, prehispanolone LC-5504 and Con A and LPS on T cells and B cells proliferation of BALB/c female mice in vitro. They showed that: (1) proliferation of T cells was demonstrated by administration of LC-5504 of various concentrations together with Con A. This proliferation was 5-8 times stronger than that observed when Con A was used alone. Such effect on T cells was not observed when LC-5504 was used alone. (2) Proliferation of B cells was not observed whether LC-5504 was used alone or together with LPS. PMID- 1300025 TI - Synthesis, antiinflammatory and anticancer activity of cinnamic acids, their derivatives and analogues. AB - Cinnamic acids were selected as lead compounds of antiinflammatory and anticancer agents through the investigation of their biological properties. Their esters and related styryl ketones were also studied. A total of nineteen compounds, fifteen of them not reported previously, were synthesized and found to be of considerable pharmacological interest. In preliminary biological tests, compounds IA, IB, IC, II2C and II5C showed significant inhibiting effect on croton oil induced mouse ear edema, IB, II5A, II5C and IIID exhibited good activity on HL-60 human cancer cells in vitro. It is well worth noticing that compounds IB and II5C exhibited excellent antiinflammatory action as well as anticancer activity. PMID- 1300026 TI - [Chemistry and antitumor activity of hainanensine analogues]. AB - A synthetic analogue of hainanensine 2a was further modified in order to improve its antitumor activity. Six compounds 3-8, were obtained, and among these compounds 8 showed significant activity. The diastereomer (+/-)8B was resolved by (+) tartaric acid and (-)benzoyl-tartaric acid to the corresponding enantiomers ( )8B and (+)8B, respectively and their optical purities were determined by isotope dilution method as 93% and 96%. The antitumor activity of the newly obtained compounds were tested in vitro, and (-)8B was found to have an IC50 of 1.9 mol/L, eighteen times higher than the original compound 2a. PMID- 1300027 TI - [Structure modification of triptolide, a diterpenoid from Tripterygium wilfordii]. AB - In this paper, the structure modification of triptolide was studied and nine triptolide derivatives were synthesized. A preliminary test for the immunosuppression activity in vitro showed that tripchlorolide (2) and tripbromolide (3) have strong activity similar to triptolide, while their toxicity are much lower. The activity of other compounds was decreased significantly. A simple method for the preparation of tripchlorolide from triptolide in 92% yield was found by reacting triptolide with HCl in acetone under mild condition. PMID- 1300028 TI - [Study on the chemical composition of leaves and stalks of Trollius macropetalus]. AB - A new constituent and four known compounds have been separated from the dry leaves and stalks of Trollius macropetalus Fr. Schmidt. By means of physico chemical and spectroscopic methods, the structures of these compounds have been determined as vitexin-2''-O-beta-D-pyranxyloside (I), orientin-2''-O-beta-D pyranxyloside (II), vitexin (III), orientin (IV) and 3-methoxy-4-hydroxyl-5-(3' methyl-2'-)butylenzylbenzoic acid (V). I and II are found in the Trollius genus for the first time, V is a new compound named proglobeflowery acid. PMID- 1300030 TI - [HPLC determination of salidroside in the roots of Rhodiola genus plants]. AB - This paper reports a high performance liquid chromatographic (PHLC) method for the determination of salidroside in 10 samples of the plants of Rhodiola crenulata, R. alterna, R. brevipetiolata, R. yunnanensis and R. quadrifida as well as extracts of R. crenulata. Determination was carried out under the following conditions: column (mu Bondapak ODS, 10 microns, 3.9 mm x 300 mm), mobile phase (methanol-water, 2:8), flow rate (1.0 ml/min), detector (Waters 484, wavelength 276 nm). External standard method was used. The results show that HPLC is a useful tool for the quantitative analysis of salidroside in the plants of Rhodiola genus and the extracts of R. crenulata. PMID- 1300029 TI - [Studies on the sweet principles from the leaves of Cyclocarya paliurus (Batal.) Iljinskaya]. AB - Four intensely sweet compounds (I-IV) were obtained from the leaves of Cyclocarya paliurus (Batal.) Iljinskaya. The structure of compound I was elucidated by chemical and spectroscopic methods as 20,24-epoxy-dammarane-(3 beta,12 beta,24R) 12-O-alpha-L-rhamnopyranosyl-25- hydroxyl-3-O-alpha-(5'-O-acetyl)-L arabinofuranoside. It is a new natural product, named cyclocarioside A, and is the main sweet principle of this plant, possessing about 200 times the sweetness intensity of sugar. PMID- 1300031 TI - [The identification and determination of marker substances in xiaoyao wan by three dimensional HPLC]. AB - A Chinese traditional patent medicine Xiaoyao Wan was analysed by three dimensional HPLC. The result shows that the Chinese traditional medicines involved in Xiaoyao Wan were identified excellently and the content of marker substances can be determined accurately. According to the results of determination, the content of saikosaponin b1, b2, glycyrrhizin, paeoniflorin and atractylenolide III in Xiaoyao Wan was 0.43, 0.53, 5.22, 3.95 and 0.16 (mg/g), respectively; The RSD was 1.2, 0.8, 0.4, 0.3 and 1.0 (%) respectively. PMID- 1300032 TI - [Studies on transdermal delivery system of isosorbide dinitrate]. AB - A transdermal delivery system of isosorbide dinitrate (ISDN-TDS) and an HPLC method for the measurement of ISDN were developed. The system is composed of backing, drug reservoir, control membrane, contact adhesive and protective layer. The influences of drug reservoir, solvent, control membrane, viscosity and penetration enhancer azone on the release of ISDN were investigated. The cumulative released amount of ISDN/time profile indicated that ISDN was permeated through excised skin in a zero-order kinetic in 48 h. The release of ISDN from ISDN-TDS can last 72 h at least. The mean permeation rate is 13.76 micrograms.h 1/cm2. Releasing ISDN from ISDN-TDS was more stable than that from Frandol tape-s whose release profile was found to follow a linear Q vs t1/2 relationship with a release flux of 114.39 micrograms.h-1/cm2. PMID- 1300033 TI - [The crystal structure of triptophenolide revisited]. AB - Triptophenolide, C20H24O3, has been assigned two isomeric structures. DF Yu et al reported the X-ray analytical structure II in 1990. In 1982, however, FX Deng et al had already reported the spectrometric assignment of structure I. Now, we report again the single crystal analysis of triptophenolide (I). The crystal belongs to space group P2(1)2(1)2(1) of orthorhombic system, with a = 7.270(6), b = 12.509(8), c = 36.20(1) A, Z = 8. The structure was solved by direct method and refined by the full-matrix least-square method to a final R factor 0.055, based on 2322 intensities with I > or = 3 sigma (I). It is highly probable that the result of DF Yu was in error with only 1292 available intensities. PMID- 1300034 TI - [Application of derivative spectrophotometric signal multiplier method in multicomponent mixture--determination of moroxydine hydrochloride in Gan Mao Qing capsules]. AB - This paper provides a basic principle and experimental technique of derivative signal multiplier spectrophotometry in multicomponent mixture. A microcomputer was used to process the spectral data measured on a manual spectrophotometer (UV 7520) for the determination of moroxydine hydrochloride in Gan Mao Qing capsules. Quantitative analysis of multicomponent mixture can be done without sample separation. The selection of optimal wavelength pairs is performed through the program with a computer. The method needs no special spectrophotometer and is simple, rapid and easy to operate. The mean recovery was 99.98 +/- 0.53% (n = 12). PMID- 1300035 TI - [Solid-phase extraction and RP-HPLC screening procedure for diuretics, probenecid, caffeine and pemoline in urine]. AB - A solid-phase extraction and reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for the rapid determination of 13 diuretics (belonging to five different pharmacological groups), probenecid, caffeine and pemoline in urine. Two ml urine sample was first adsorbed on a XAD-2 column, then eluted with ether-ethyl acetate (1:1). The eluate was evaporated to dryness and reconstituted in methanol. The methanolic solution was injected into a HP LiChrosorb RP-18 column, using phosphate buffer (pH 3) and acetonitrile as the mobile phase and monitored at 216 nm, 230 nm, and 275 nm on a diode array ultraviolet detector. The extraction recoveries of 16 drugs were above 75%. The limits of detection ranged from 0.3-3.0 micrograms/ml of urine. All drugs were separately administered to healthy volunteers, positive urine samples were collected, and urinary excretion-time curves of some drugs were reported. PMID- 1300036 TI - Tetrandrine is not a selective calcium channel blocker in vascular smooth muscle. AB - The effects of tetrandrine (Tet) on the contractile properties of rat aortic ring preparations were studied to test the hypothesis that Tet is a Ca2+ antagonist acting on voltage-operated Ca2+ channels (VOC). The tests were performed on contractions induced by depolarizing concentrations of KCl and by alpha 1 adrenoceptor agonist, phenylephrine (Phe). These vascular effects of Tet were compared to those of nifedipine (Nif). We found that Tet behaved qualitatively similar to, but less potent than, Nif in that it inhibited KCl-induced contraction in a concentration-dependent fashion and its inhibitory effect was long-lasting. However, the effects on Phe-induced contraction of Tet was different from those of Nif in that the extracellular Ca(2+)-dependent contraction was inhibited by Tet, but not by Nif. Tet (60 mumol.L-1) completely inhibited the 45Ca2+ uptake induced by KCl and Phe in rat aortic muscle strips. When the aortic muscle contractile response was induced by addition of Ca2+ following depletion of intracellular stores by Phe in the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, Tet (60 mumol.L 1) was more effective than Nif 1 mumol.L-1 in inhibiting such a response to extracellularly added Ca2+. Furthermore, Tet, but not Nif, also significantly inhibited the contraction to Phe in Ca(2+)-free medium. Collectively, these results led us to conclude that Tet does not behave as a selective VOC blocker like Nif. PMID- 1300037 TI - Effect of cimetidine and ranitidine on absorption of [125I]levothyroxine administered orally. AB - Female patients with a simple goiter were pretreated on 2 occasions (at an interval of 4 wk) with po placebo or 400 mg cimetidine (Cim) (Group A, n = 10), or with placebo or 30 mg ranitidine (Ran) (Group B, n = 10), 90 and 150 min, respectively, prior to the po gelatin capsules containing [125I]levothyroxine ([125I]LT4). A double-blind randomized study protocol was kept. Venous blood samples were taken at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 min after po [125I]LT4 and the radioactivities in serum were counted. Similar [125I]LT4 radioactivities were found after placebo pretreatment in both groups: AUC 467 +/- 82 in Group A vs 459 +/- 109 in Group B. Cimetidine decreased the serum [125I]LT4 radioactivities: AUC371 +/- 72 (Cim) vs 467 +/- 82 (placebo) (P < 0.01), but Ran did not: AUC 477 +/- 132 (Ran) vs 459 +/- 109 (placebo) (P > 0.05). PMID- 1300038 TI - Effects of (-)-stepholidine on firing activity of dopamine neurons in ventral tegmental area of rats. AB - Extracellular single-unit recording techniques were used to evaluate the effects of (-)-stepholidine (SPD) on the firing activity of ventral tegmental area (VTA) dopamine (DA) neurons. SPD reversed the DA agonist apomorphine (Apo)-induced inhibition of VTA DA cell firing rate (ED50 = 4.9, 4.5-5.3 micrograms.kg-1), and the reversal was more rapid than that of a classic DA antagonist haloperidol (Hal) (ED50 = 11.2, 9.1-13.8 micrograms.kg-1). Pretreatment with SPD or Hal 0.5 mg.kg-1 attenuated Apo-induced inhibition, and SPD rendered the VTA DA cells less sensitive to larger doses of Apo (1024-4096 micrograms.kg-1) than Hal did. Pharmacological analysis indicated that the effects of SPD were mainly mediated through D2 subtype receptors. In addition, SPD increased the firing rate of VTA DA cells, while higher doses (1.4, 0.6-3.3 mg.kg-1) of SPD dramatically inactivated 4/6 of the VTA DA cells sampled. This inhibition was considered to be due to depolarization inactivation. These results suggest that SPD is a DA receptor antagonist and can effectively block the D2 autoreceptors located in the VTA DA cells. PMID- 1300039 TI - Effects of neuropeptide Y injected into A1 noradrenergic nucleus on blood pressure and catecholamines in plasma of cats. AB - The microinjection of neuropeptide Y (NPY) 0.75 and 1.5 micrograms into A1 noradrenergic nucleus of cats produced dose-dependent falls in mean arterial blood pressure of 2.0 +/- 0.6 and 4.9 +/- 2.4 kPa, respectively. NPY microinjection (1.5 micrograms) also produced marked decreases in noradrenaline (5 +/- 4 pmol.ml-1) and adrenaline (23 +/- 8 pmol.ml-1), but no significant change in dopamine in blood plasma. The results suggest that the depressor effect of NPY in A1 noradrenergic nucleus may be realized by not only reducing the release of noradrenaline in sympathetic terminals around the peripheral vascular beds but also inhibiting the sympathetico-adrenal system. PMID- 1300040 TI - Influences of ginsenosides Rb1, Rb2, and Rb3 on electric and contractile activities of normal and damaged cultured myocardiocytes. AB - Free radical damage to the cultured myocardiocytes of Wistar rat was induced by adding xanthine 0.42 mmol.L-1 and xanthine oxidase 5.3 nmol.L-1 to the culture medium. 30 micrograms.ml-1 of Rb1, Rb2 or Rb3 extracted from the leaf and stem of Panax ginseng C A Meyer restored the action potentials (AP) of free radical damaged cells to normal, indicating their antioxidative action. On normal myocardial cells, Rb1, Rb2, Rb3 20 micrograms.ml-1 inhibited the AP and spontaneous contractility, (suggesting the Ca channel blockade action of panaxadiol saponins). The degrees of their inhibitory effects were found to be Rb1 > Rb2 > Rb3. Their effects against X-XO were basically the same. PMID- 1300041 TI - Frequency-dependent depression of Vmax in K(+)-depolarized guinea pig papillary muscle by tetrandrine. AB - The effect of tetrandrine (Tet), a calcium antagonist, on the maximal upstroke velocity (Vmax) of depolarization in K(+)-depolarized guinea pig papillary muscles was studied by standard microelectrode method with computer. The results showed that: (1) the resting block of Tet on Vmax was concentration dependent; (2) the drug (50 or 100 mumol.L-1) caused a marked frequency-dependent block of Vmax, which accounted for 65 +/- 8% of total block at a concentration of 100 mumol.L-1 and the pacing frequency of 0.3 Hz; (3) the recovery kinetics of Vmax could be characterized as a biexponential function, of which the second phase was prolonged by the drug; (4) compared with verapamil, nitrendipine, and diltiazem, the above-mentioned effects of Tet on Vmax were similar to those of diltiazem. These results suggest that Tet can block calcium channel in both frequency dependent and frequency-independent manner, mainly the former. PMID- 1300042 TI - Effects of berbamine on contraction and Ca2+ influx of pig basilar artery. AB - Effects of berbamine (Ber) on KCl- and 5-HT-induced contraction of basilar artery (BA) of pigs were studied in vitro. Ber relaxed markedly KCl-induced contraction of BA (IC50 = 4.63 mumol.L-1) and its effect was antagonized by increasing the concentration of extracellular Ca2+; Ber inhibited 5-HT-induced contraction of BA, showing significant inhibition of sustained tonic contraction (STC) (IC50 = 0.64 mumol.L-1) whereas the initial fast phasic contraction (FPC) was relatively unaffected (IC50 = 19.8 mumol.L-1); the 5-HT-induced contraction of BA was dependent on the concentration of extracellular Ca2+, especially STC. The results of Ca2+ withdrawal and replacement indicated that STC was due to 5-HT-stimulated Ca2+ influx, while 5-HT-induced release of intracellular Ca2+ resulted in FPC. Ber 0.8 mumol.L-1 produced markedly inhibitory effect on Ca2+ influx induced by 5 HT (P < 0.01). The effects of Ber were similar to those of nimodipine (Nim). The present results suggested that Ber has antagonistic effect on the potential sensitive channels (PSC) and the receptor operated channels (ROC). PMID- 1300044 TI - Effects of tetrandrine on action potentials and afterhyperpolarization potentials in toad dorsal root ganglia. AB - Intracellular recordings were obtained from the cytosome of type A primary afferents in the isolated toad dorsal root ganglia (DRG) preparations. Bath application of Ca2+ 8.0 mmol.L-1 led to prolong action potential duration of repolarization 100% (APD100) by 23%, afterhyperpolarization potential duration of depolarization 50% (AHPD50) by 46%, and increase afterhyperpolarization potential amplitude (AHPA) by 40%. Verapamil 3 mumol.L-1 shortened the APD100 by 7% and the AHPD50 by 13%, and reduced the AHPA by 17%. The effects of Tet 3-100 mumol.L-1 consisted of APD and AHPD50 shortening and AHPA reduction in concentration dependent manner. Tet 100 mumol.L-1, APD100 was shortened by 16%, AHPD50 by 18%, and AHPA was reduced by 20%. The results suggested that the effects of Tet may be related to its Ca2+ channel blockade in DRG. PMID- 1300043 TI - Reversal of doxorubicin resistance by tetrandrine in Chinese hamster ovary cell line. AB - Tetrandrine (Tet) 0.5 microgram.ml-1 and 1 microgram.ml-1 potentiated 2.88- and 4.3-fold growth-inhibitory effects of doxorubicin (Dox) in Chinese hamster ovary cell line (CHO), respectively, while Tet 1 microgram.ml-1 and 2.5 micrograms.ml-1 potentiated 7.3- and 8.4-fold in its resistant cell line (CHO/Dox), respectively. The colony-forming efficiencies were reduced in CHO and CHO/Dox when the cells were treated with noncytotoxic doses of Tet 2.5 micrograms.ml-1 and 5 micrograms.ml-1 in combination with different concentration of Dox. Increase in accumulation of Dox in CHO/Dox cells was shown by fluorometry. The result indicated that Tet reversed the resistance to Dox in CHO/Dox cells. PMID- 1300045 TI - Effects of exogenous gamma-aminobutyric acid on experimental arrhythmias. AB - The effects of exogenous gamma-aminobutyric acid (GABA) 10 mg.kg-1 iv in preventing arrhythmias induced by drugs and ischemia were studied in mice, rats, and guinea pigs. It was found that the threshold dose of aconitine inducing arrhythmia in mice and the recovery rate to normal sinus rhythm increased significantly, ED50 of GABA was 5.4-5.8 mg.kg-1. The duration of ventricular tachycardia (VT) induced by aconitine in rats was shortened (P < 0.01). The incidence and the mortality of ventricular fibrillation (VF) in GABA group were decreased to 0/10 vs 6/10 and 5/10 in control, respectively (P < 0.05). The doses of ouabain to induce ectopic beats (EB), VT, VF, and cardiac arrest (CA) in guinea pigs were increased (P < 0.01). The incidence of VF induced by coronary artery ligation in rats was decreased to 0/5 in GABA group vs 4/5 in control group (P < 0.01). The total amount of EB, total time of VT, and VF were 66%, 41%, and 0% of the control group, respectively. The anti-arrhythmic effects of GABA were dose-dependent and as potent as procainamide (10 or 5 mg.kg-1, iv). The results suggest GABA (10 mg.kg-1, iv) may be useful for the prevention of VT and VF. PMID- 1300047 TI - Rat liver microsomal and mitochondrial metabolism of primaquine in vitro. AB - The profiles of major metabolites of primaquine (PQ) produced from liver microsomal (MC) and mitochondrial (MT) metabolism were investigated in vitro by silica gel thin layer and reverse phase high pressure liquid chromatography (HPLC). The results indicated that 5-hydroxy primaquine (5-OH PQ) and carboxyprimaquine (CPQ) were simultaneously produced by either microsomes or pure mitochondria preparations. However, the quantitative study showed that microsomes produced approximately 19 times more 5-OH PQ but only 1/34 of the CPQ by mitochondria. PMID- 1300046 TI - Scavenging effects of phenylpropanoid glycosides on superoxide and its antioxidation effect. AB - The antioxidative activities of six phenylpropaniod glycosides (PPG) extracted from Pedicularis striata and Pedicularis lasiophrys for inhibiting the lipid peroxidation induced by Fe2+/ascorbic acid in mouse liver microsome may be related to the number and steric position of phenolic hydroxyl groups (PHG) they possess (32.5 mumol.L-1 to 65.0 mumol.L-1). The scavenging effects of PPG for superoxide produced by NBT/PMS/NADH system may be related to both the number of PHG and their conjugated system (16.0 mumol.L-1 to 65.0 mumol.L-1). PMID- 1300049 TI - Thrombolytic actions of reptilase. AB - In thrombolytic model in vitro, reptilase (Rep, defibrase) did not show appreciable thrombolytic actions on red and white thrombi. After daily iv infusion of Rep 0.25 IU for 10 d, the time of 50% lysis of euglobulin (ELT1/2) was shortened from 9.3 +/- 0.8 to 6.7 +/- 1.0 h (P < 0.01), alteplase activity was increased from 1.9 +/- 0.7 to 3.7 +/- 0.9 IU.ml-1, and plasminogen inactivator (PI) activity reduced from 4.3 +/- 0.6 to 1.8 +/- 0.9 AU.ml-1 (all P < 0.01). The findings indicate that the thrombolytic action of Rep shown in vivo may not be from the direct action on thrombi but from the influence on alteplase and PI activity. PMID- 1300048 TI - Antitumor effects of new-type recombinant interleukin-2. AB - Two new human recombinant interleukin-2 (rIL-2), 125-Ser-rIL-2, and 125-Ala-rIL 2, were generated by protein engineering technique. Both of them maintained the proliferation of natural killer (NK) cells, CTLL-2 cells and their long-term propagations. The mutated new rIL-2 also enhanced the bioactivity of NK cells and the cytotoxicity of tumor-infiltrating lymphocytes (TIL) against the target tumor cells. The above results were all compared with that of the native rIL-2 and a similarity between them was found, which indicates that new type rIL-2 could be used for adoptive immunotherapy of malignant diseases. PMID- 1300050 TI - [Feed-back regulation of presynaptic D2 receptors blockaded by l-stepholidine and l-tetrahydropalmatine]. AB - The activity of tyrosine hydroxylase by accumulation of L-dopa content in the striatum under decarboxylase inhibitor (benserazide, 400 mg.kg-1) was measured by HPLC-ECD to ascertain whether l-SPD possesses an agonistic or antagonistic effect on D2 receptor subtype. The accumulated L-dopa content was increased with 1,4 butyrolactone (BL, 750 mg.kg-1) to 1.8 +/- s 0.6 micrograms.g-1 in rat striatum. After the rats were ip l-SPD 5 mg.kg-1 or l-tetrahydropalmatine (l-THP) 10-20 mg.kg-1, the increment of L-dopa level was much more than that in the BL group (P < 0.01) in a dose related manner. On the contrary, apomorphine (ip 5 mg.kg-1) abolished the accumulation of L-dopa induced by BL. Furthermore, l-SPD and l-THP not only reversed the negative feed-back regulation by apomorphine on the accumulated level of L-dopa, but also increased this level over the accumulation by BL. These results showed that l-SPD and l-THP do possess the antagonistic effect on presynaptic DA receptor (D2) without agonistic effect. PMID- 1300051 TI - [Antihypertensive effects of atenolol and nitrendipine alone or in combination on three hypertensive models of rats]. AB - The antihypertensive effects of atenolol (Ate) or nitrendipine (Nit) alone or in combination (Ate+Nit) were studied in conscious experimental hypertensive rats. The hypotensive effects of single ig of Ate 20 + Nit 10 mg.kg-1 were rapid and persistent in spontaneously hypertensive rats (SHR). In renovascular hypertensive rats (RVHR) and DOCA-salt hypertensive rats (DHR), Ate+Nit (6 + 3, 20 + 10, 60 + 30 mg.kg-1) given ig once a day for 10 d reduced the blood pressure in a dose dependent manner. But Ate 20 mg.kg-1 or Nit 10 mg.kg-1 alone given ig once a day for 10 d caused no obvious reduction in blood pressure in RVHR, DHR, and SHR q = 1.32. These results revealed that the synergy is present in the antihypertensive action of Ate+Nit. PMID- 1300052 TI - [Effects of imipramine on isolated rabbit basilar artery]. AB - Imipramine (Imi) inhibited the contractile response to BAY k 8644 (IC50 = 2.39 +/ 0.33 mumol.L-1), KCl (IC50 = 1.00 +/- 0.09 mumol.L-1), in rabbit basilar artery rings. Imi was more effective in suppressing the contractile response evoked by KCl, CaCl2, and 5-HT in basilar artery rings than in mesenteric artery rings. The effect of Imi was the same as that of diltiazem (Dil). There was no difference between the inhibitory response of Imi on contraction induced by KCl in basilar artery rings with or without endothelium. The results suggest that Imi may block the calcium channel and inhibit the rabbit basilar artery selectively, and the effect is endothelium-independent. PMID- 1300053 TI - [Excitant effect of sodium suberogorgin on isolated rabbit ileum]. AB - Suberogorgin was isolated from Gorgoniae suberogorgia sp from South China Sea. The isolated rabbit ileum contracted in a concentration-dependent manner by suberogorgin-Na (Sub) 2.13 mumol.L-1 or higher. Sub 213 mumol.L-1 had no effect on the relaxation induced by norepinephrine and isoprenaline 10-100 mumol.L-1 on ileum. The stimulation of Sub on ileum was antagonized by atropine 56 mumol.L-1 or indometacin 0.35 mmol.L-1 and was partly blocked by indometacin 0.17 mmol.L-1, but was not affected by diphenhydramine 10 mumol.L-1. On the contracted ileum induced by neostigmine 1.7 mumol.L-1, acetylcholine 0.1 mumol.L-1 increased the tension but Sub 213 mumolL-1 did not. Sub obviously inhibited the acetylcholinesterase (AChE) from mouse brain hemogenates in vitro. Its pI50 (negative logarithm of molar concentration causing 50% inhibition of AChE) was 4.18, while the pI50 of neostigmine was 4.75. The results indicated that the ileum-excitant action of Sub was chiefly related to the inhibition of AChE. PMID- 1300054 TI - [Nuclear anomaly test in human lymphocytes in vitro]. AB - To assess the usefulness and the sensitivity of the nuclear anomaly test in human lymphocytes we treated in vitro human whole blood with various concentrations of mitomycin C, thiotepa, and bimolane. After the blood samples had been stored at 37 degrees C for 17-18 h, smears of isolated lymphocytes were made. The nuclear anomalies (micronuclei, irregular, karyorrhectic, and pyknotic nuclei) were measured. The concentration-response relationship and the minimum sensitive concentration of nuclear damage indices to the test mutagens were analyzed. The results showed that all 3 drugs induced a concentration-dependent increase of other nuclear anomalies except pyknotic nucleus in lymphocytes, that the most sensitive index of nuclear damage was the micronucleus assay, that the karyorrhectic assay was as sensitive to MMC and bimolane as the micronucleus assay, and that the irregular nucleus assay and the complex nuclear anomaly assay were less sensitive, but the correlation between concentration and complex nuclear anomalies was the best among various indices of nuclear damage. Therefore, the in vitro nuclear anomaly test in lymphocytes of human whole blood could be used to evaluate genotoxic effects of chemicals. PMID- 1300055 TI - [Pharmacokinetics of epostane in rabbits by HPLC method]. AB - Epostane (Epo), a 3 beta-hydroxysteroid dehydrogenase inhibitor, interrupted pregnancy in rats, rhesus monkeys, and women. Epo concentrations in serum were determined by high performance liquid chromatography (HPLC) at 0.25, 0.5, 1, 2, 4, 8, 16, 32, and 48 h after intragastric Epo 96 mg.kg-1 in rabbits. The concentration-time curve exhibited a 2-compartment open model. The pharmacokinetic parameters were: T1/2ka 0.79 +/- 0.08 h, T1/2 alpha 0.96 +/- 0.08 h, T1/2 beta 6.6 +/- 1.5 h, Vc 14 +/- 3 ml.kg-1, AUC 12.0 +/- 1.9 micrograms.h.ml 1, Tmax 1.8 +/- 0.5 h, Cmax 3.3 +/- 0.5 microgram.ml-1. After rat copora luteum were incubated with hCG 10 IU.ml-1 and Epo 10 or 100 micrograms.ml-1 for 18 and 48 h, luteal cells showed various degrees of degeneration and progesterone production was significantly inhibited. PMID- 1300056 TI - [Enhancement of antitumor activity of harringtonine in human leukemia-60 cells in vitro by verapamil]. AB - The effect of harringtonine (Har) alone and in combination with verapamil (Ver) on the proliferation of human leukemia-60 (HL-60) cells in vitro were studied. IC50 of Har alone to the cells was about 49 ng.ml-1 which was reduced to its 1/3.3 and 1/4.5 when used with Ver 1 and 2 micrograms.ml-1, respectively. In colony forming test, the survival fraction of the HL-60 cells treated with Har 15 and 30 ng.ml-1 plus Ver 2 micrograms.ml-1 was reduced to 1/3.3 and 1/8 of the cells as when treated with Har alone, respectively. The results suggested that Ver enhanced the antitumor activity of Har in vitro and may used as an enhancer of Har in vivo. PMID- 1300057 TI - [Effect of mebendazole on glucose uptake of Echinococcus granulosus cysts]. AB - Mice infected with secondary cysts of Echinococcus granulosus were treated ig with mebendazole (Meb) 25 mg.kg-1.d-1 for 7-14 d. At 24 h after the last dose the endocysts in the treated mice were removed out for in vitro cultivation and exposed to [U-14C]glucose 11.1 kBq.ml-1 for 2 min, no apparent difference in radioactivity content in the cyst walls between the treated and control groups was observed. When [U-14C]glucose was given iv to the infected mice 24 h after they had been treated ig with Meb 25 mg.kg-1 or 50 mg.kg-1 daily for 14 d, the radioactivity content in the cyst wall and cyst fluid decreased significantly as compared to the corresponding control group. Nevertheless, no apparent change in the incorporation of radioactivity into the endogenous glycogen of the parasites was observed, although the glycogen in the cyst wall decreased markedly. PMID- 1300058 TI - [Effects of dexamethasone and cyclophosphamide on development of exo-erythrocytic form of Plasmodium cynomolgi bastianellii in rhesus monkey]. AB - The rhesus monkeys (Macaca mulatta) challenged with Plasmodium cynomolgi bastianellii sporozoites were treated with im dexamethasone (Dex) 1 mg.kg-1.d-1 x 7 d and cyclophosphamide (Cyc) 25 mg.kg-1.d-1 x 3d, respectively. On d 7 after challenge, serial sections of liver biopsy stained with HE revealed that the distributive density and size of exo-erythrocytic (EE) form of the parasites showed no difference between medicated and control monkeys. The prepatent period of the primary attack and the relapse patterns after the treatment of Dex and Cyc were also similar to each other. The radically cured monkeys challenged with the Plasmodium erythrocytic form were reinfected with sporozoites, the relapses were much less than those in control monkeys, but the density and size of EE form in liver were similar to those in control monkeys. These results suggest that Dex and Cyc exert no effect on the development of EE form (including hypnozoite) in the monkeys. PMID- 1300060 TI - [Hemodynamic parameters in the severely burnt patient during the 1st 72 hours]. AB - The haemodynamic time course of 16 patients with severe burn injury was investigated using a flow-directed balloon-tipped pulmonary artery catheter. The patients, aged 33.8 +/- 5.5 years, were burnt over 60 +/- 10% of body surface area, with a UBS score of 228 +/- 43. The measurements were obtained every six hours after insertion of the catheter. Fluid load was determined with Evans' formula, and modified according to the haemodynamic data. Catecholamines were introduced when this and a trial of fluid loading with 5 ml.kg-1 of macromolecules during a 20 min period had failed, starting with dobutamine or dopamine, followed by adrenaline as required. During the first hours after the injury, circulatory shock was partly linked to hypovolaemia: mean arterial pressure was 60.1 +/- 7.8 mmHg, right auricular pressure 4.5 +/- 2 mmHg, pulmonary wedge pressure 4.7 +/- 2 mmHg, cardiac index 3.5 +/- 0.8 l.min-1 x m-2. However, during the second and third days, cardiac output increased, with a cardiac index at 4.7 +/- 0.6 l.min-1 x m-2 and 5.2 +/- 0.2 l.min-1 x m-2 respectively, and arterial vascular resistances were decreased (536 +/- 125 dyn.s.cm-5). These data suggest a specific haemodynamic profile in severe burn patients which justifies invasive monitoring, and the use of catecholamines, in those patients that do not respond to fluid loading. The link between these data and the concomitant metabolic disturbances due to the burn injury has not yet been established. The increase in cardiac index could be related to the inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300061 TI - [Epidural anesthesia and metabolic response to surgical stress]. AB - Surgical stress leads to reproducible physiological metabolic and hormonal responses, characterized by on altered carbohydrate metabolism, a net loss of protein and an increased lipolysis. They are due to an increased secretion of catecholamines, ACTH, cortisol and cytokines. Epidural analgesia prevents the hyperglycaemic, cortisol and adrenocortical responses to surgery. The lipolysis and the loss of protein are also attenuated. This effect only occurs in lower abdominal surgery, with an epidural blockade extending from T4 to S5, carried out with local anesthetic agents and started before the skin incision. However, such a blockade abates, but does not suppress, the metabolic response to upper abdominal or thoracic surgery, probably because of persistent vagal afferences, the incomplete blockade of somatic afferents, and a stimulation of the diaphragm and peritoneal free nerve endings. Likewise, epidural morphine does not modify the intraoperative metabolic and hormonal responses. The main reason is most probably the failure of opioids to block the sympathetic system, as well as their insignificant effects on fast conducting fibers. PMID- 1300059 TI - [Vascular effects of urapidil administrated during extracorporeal circulation]. AB - Urapidil exerts a combined central sympathetic and peripheral alpha-1 adrenergic receptor inhibition. Urapidil induces arterial vasodilation but its effects on venous capacitance are more difficult to assess. During cardiopulmonary bypass with constant perfusion index (2.4 l.min-1 x m-2) total peripheral resistance varies similarly as to arterial pressure and, as the apparatus venous reservoir is filled continuously by simple gravity from the right atrium, a decrease in venous blood reservoir level reflects an increased venous capacitance. Twenty-six patients undergoing cardiac surgery were anaesthetized with fentanyl and midazolam and randomly assigned to one of two groups. During normothermic cardiopulmonary bypass, group 1 was administered i.v. urapidil 12.5 mg and group 2 a placebo. In group 1, arterial pressure decreased by 33 +/- 14% (mean +/- SD) at the second minute while total peripheral resistance decreased from 1,384 +/- 255 to 927 +/- 193 dyn.s.cm-5. Then this two parameters regained group 2 values after the eighth minute. Reservoir blood level was lower in group 1 than in group 2 from the second to the eight minute (p < 0.05) with maximum effect at 7 minutes. It is concluded that urapidil exerts arterial and venous dilation. Its arterial effects seem greater during normothermic cardiopulmonary bypass than in normal conditions and its maximum venous effects seem to occur after its maximum arterial effects. The short duration of action may be due to the small dose administered. PMID- 1300063 TI - [Effects of continuous administration of nimodipine during the acute phase of spinal cord injury in baboons]. AB - This study was carried out to assess the putative improvement of spinal cord blood flow obtained with a calcium channel blocker after acute spinal cord injury in ten baboons. The injury was generated by compressing the cord at L1 level for 5 seconds with a balloon catheter inflated to 2 bars with Ringer's solution. Subsequently, five monkeys received a saline infusion, and five others a nimodipine infusion (0.04 mg.kg-1 x h-1), for seven days. Spinal cord blood flow (SCBF) was measured using a scanographic technique with stable xenon. Somatosensory evoked potentials (SEP), magnetic resonance imaging (MRI) and a histological study of the spine were carried out a different times of the study. SCBF and SEP were recorded before injury. Thereafter SCBF was measured every thirty minutes during the four hours following the injury, as well as on day 7. SEP and MRI were recorded on days 1 and 7. The histological study was carried out on the eighth day. Three spinal cord and vertebral segments were collected, fixed, sliced and stained. SCBF before injury was not significantly different in either group (39.8 +/- 15.9 ml x 100 g-1 x min-1 for the treatment group 40.9 +/- 16.3 ml x 100 g-1 x min-1 for the control group). During the injury, there were major variations between animals. The results were expressed as percentages of each animal's control SCBF (before injury). Immediately after injury, SCBF increased in both groups. However, in the control group, SCBF decreased more than in the treatment group on the seventh day after injury (80 to 90% vs 25 to 50%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300062 TI - [Methods for measuring spinal cord blood flow]. AB - This study aimed to review the techniques used most currently for measuring spinal cord blood blow flow (SCBF) in animals, i.e. the hydrogen clearance, labelled microspheres, 133Xe clearance and 14C-antipyrine autoradiographic methods. All four techniques may only be used in animals, because of their invasiveness. Flow figures varied greatly with the method, the spinal level at which measurements were carried out, and the species of animal. However, results tend to suggest that SCBF is very similar to cerebral blood flow in that it is controlled by chemical, autoregulatory and metabolic factors. Approaches to measuring SCBF in man may be made using stable xenon-enhanced computed tomographic imaging (Xes-CT) in the same way as for measuring cerebral blood flow. The calculation of SCBF is based on Fick's principle transformed by Kety and Schmidt. After a reference CT section has been obtained, twelve 8 mm thick sections are carried out whilst the patient breathes a 30% xenon-70% air/oxygen mixture. This series of views enables the SCBF to be calculated in four steps. Quantitative analysis in eight human subjects gave a mean SCBF of 58.8 +/- 5.96 ml x 100 g-1 x min-1. However, this method has a low signal to noise ratio. Moreover, the qualitative analysis of the parametric views of flow demonstrate tissue heterogeneity, partly due to the patient's movements (breathing movements). However, the method is non invasive, safe, and reproducible. As it can measure very low values of blood flow, the study of ischaemic spinal lesions is made possible, although some technical and software improvements are still required. PMID- 1300064 TI - [Anesthesia of patients with injury to the cervical spine]. AB - This paper reviews the principal aspects of the immediate management of patients suffering from spinal injury. An understanding of the pathophysiology of primary and secondary spinal cord injury enables appropriate initial care to be provided, thereby avoiding exacerbation and/or progressive deterioration of the lesion. It includes protective measures, restoration of vital functions to maintain adequate tissue perfusion and oxygenation, as well as pharmacological prevention of secondary injury. Protective measures include proper immobilisation of the spine with a semi-rigid collar and tape on a long backboard, or on vacuum mattress, taking great care to avoid deleterious in-line compression forces on the spinal column. The combination of cervical spine instability, a full stomach, unopposed vagal reflexes, hypoxia and hypercarbia makes airway management of these patients difficult. Tracheal intubation under fibroscopic control, with insertion of the tube only after topical anaesthesia of the airways under titrated intravenous sedation, offers safety and comfort to the patient. However, in cases of severe deterioration of vital functions, intubation must be performed without any delay at the site of the accident or in the emergency room. Three options are available: blind naso-tracheal intubation with spontaneous breathing, modified rapid sequence induction with orotracheal intubation under double protection, and immediate surgical airway if these techniques fail. Patients with cervical spine injury may demonstrate severe hypotension requiring sympathomimetic agents and careful fluid loading to avoid pulmonary oedema. To prevent aggravation of the spinal cord injury by systemic factors, the goal of initial resuscitation is to restore an adequate perfusion pressure of at least 60 mmHg, a PaO2 > 100 mmHg, and to keep PaCO2 below 45 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300065 TI - [Magnetic resonance imaging and spectroscopy of the brain: a new approach of cerebral physiopathology]. PMID- 1300067 TI - [Recovery in neurosurgery]. PMID- 1300066 TI - [Neuro-immunomodulation]. PMID- 1300068 TI - Cerebral haemodynamic and metabolic effects of hypnotics and analgesics. PMID- 1300069 TI - [Sedation and energy expenditure in brain injured patients]. PMID- 1300070 TI - [General principles of prophylactic antibiotic therapy in surgery]. PMID- 1300071 TI - [Prevention of infections in ventriculoperitoneal shunts in children]. PMID- 1300072 TI - [Antibiotic prophylaxis in craniocerebral wounds]. PMID- 1300073 TI - [Prevention of meningitis after craniotomy in scheduled surgery]. PMID- 1300074 TI - [Prevention of catheter related infections]. PMID- 1300075 TI - [Prevention of nosocomial urinary tract infection during urinary catheterization]. PMID- 1300077 TI - [Preoperative disclosing of factor XI deficiency]. PMID- 1300076 TI - [An unusual cause of severe hypocoagulation]. PMID- 1300078 TI - [Absence of recurrence with ciprofloxacin therapy of thrombocytopenia induced by pefloxacin]. PMID- 1300079 TI - [Relaxograph monitoring of severe tetanus treated with muscle relaxants]. PMID- 1300080 TI - [Systematic thoracic radiography?]. PMID- 1300081 TI - [Pathology of cranial nerves: diagnostic orientation and aphorisms]. AB - Despite the remarkable progress of Neuroradiology, the etiologic diagnosis of cranial nerve disorders remains, because of the numerous potential causes, one of the most difficult clinical problems in Neurology. It requires a perfect collaboration between neurologists, ophthalmologists, and ENT specialists, and also between clinicians and radiologists. First of all however, it is based on a rigorous clinical analysis in order to determine the site of the lesion and to guide complementary investigations. The purpose of this short paper is to provide a brief outline of this clinical approach and to recall some aphorisms which are essential to keep in mind when dealing with this pathology. PMID- 1300082 TI - [Masticatory space: radio-anatomy, pathology]. PMID- 1300083 TI - [3D imaging and pathology of the base of the skull in children]. AB - Three dimensional computed tomography was performed in 150 children suffering from a bone lesion of the base of the skull and face. These lesions were either malformative, neoplastic, infectious or traumatic. 3D CT provided an essential anatomical approach to the lesions facilitating the choice of the most appropriate treatment. 3D CT is also indicated in the follow-up of these operated children, particularly of the growth of the operated bone segment and its relations with adjacent structures. PMID- 1300084 TI - [Imaging of the facial nerve and the petrous apex]. AB - From its origin in the pons to its extracranial exit with a long intrapetrous course, the facial nerve raises various diagnostic problems related to the site and extent of the lesions, which involves the whole field of petrous pathology. The study of the pathology of the neighbouring petrous apex completes this regional analysis. Today, in accordance with the anatomical loco-regional complexity, MRI is the predominant modality of diagnostic imaging (but must be associated with CT to allow the more accurate detection of subtle bone changes); it will be at best directed by the clinical and functional data which reflect the underlying pathophysiologic mechanisms. PMID- 1300085 TI - [Neurosurgical treatment of essential facial neuralgia]. AB - The authors describe the neurosurgical techniques currently available for the treatment of essential trigeminal neuralgia refractory to the usual medical treatments. They compare the advantages and disadvantages of percutaneous techniques (particularly thermocoagulation of the trigeminal ganglion) and open techniques (especially microsurgical treatment of neurovascular conflict in the cerebellopontine angle. PMID- 1300087 TI - [Osteitis of the base of the skull]. AB - The base of the skull and calvarium may be the site of osteitis secondary to haematogenous or loco-regional dissemination of a nasal sinus or postoperative, external ear or middle ear infection. Although most of the complications of osteitis are eradicated by antibiotics, some persist and are still serious due to the delay in the diagnosis extensive necrosis due to the bacteria and the clinical context. PMID- 1300086 TI - [Anatomy of the auditory tube: CT scan and MRI aspect]. AB - The auditory tube is a bony and cartilaginous canal which connects the middle ear to the nasopharynx. The bony portion (protympanum), explored by computed tomography, is cone shaped, with a posterior base. The main relations are: the intrapetrous carotid, the tensor tympani muscle, the middle cerebral fossa and temporo-mandibular joint. The fibrocartilaginous portion is explored by computed tomography and mainly by magnetic resonance. The fibrocartilaginous tube is posteromedial; its upper margin is curled outward to form the roof of the cartilaginous tube. Anterioly and Laterally, the auditory tube is closed by a fibrous membrane extending along the inferior surface of the auditory tube to form its floor. The auditory tube is in contact with two main muscle: the tensor veli palatini anterolateral and the levator veli palatini posterolateral and inferior. They are bounded by fascia: the intrapharyngeal fascia is medial, the pharyngo basilar fascia (salpingopharyngeal fascia of Trolstch, is between the tensor and levator veli palatini muscles; the fascia of Weber Liel is lateral to the tensor veli palatini. The auditory tube and its muscles form the lateral wall of the rhinopharynx and prevent the extension of a pathologic process to the para pharyngeal and infratemporal spaces. PMID- 1300088 TI - [Diagnostic orientation and radiological assessment of anosmia]. AB - The olfactory system is made up of the olfactory epithelium, bulbs and tracts, together with olfactory areas in the brain. Anosmia may results from benign and malignant nasal sinus lesions, but also from lesions involving the CNS structures involved in olfaction. The purpose of this article is to review the different diagnose of anosmia and their CT or MR imaging characteristics. PMID- 1300090 TI - [Epidermoid cyst of the base of the skull]. AB - Epidermoid cysts are rare congenital tumours representing less than 1% of all intracranial tumours. They are derived from the development of abnormally situated ectodermal tissue and are often an incidental finding. We report a case confined to the base of the skull, responsible for an extradural mass. PMID- 1300089 TI - [Retrograde perineural extension of a metastatic recurrence of a frontal skin tumor]. AB - Perineural metastatic spread of malignant tumours has been described for a long time, but has only recently been demonstrated by medical imaging. MRI, guided by the clinical findings, with fine sections on T1-weighted sequences without and with gadolinium, allows the diagnosis of this type of spread. The tumours most frequently responsible are squamous cell carcinomas and cylindromas. The trigeminal and facial nerves are the most frequently affected. Recognition of such lesions is essential in the initial staging of a malignant tumour of the face, as it alters the therapeutic strategy. PMID- 1300091 TI - [Unusual localization of an olfactory esthesioneuroma]. AB - Olfactory neuroblastoma, a nerve tumour arising in the olfactory mucosa, is a relatively easy diagnosis in the case of a mass centered around the cribriform plate. It is more difficult to diagnose in its exceptional ectopic forms (maxillary sinus) in the absence of any cytological and histochemical arguments (fibrils, olfactory rosettes). Its local malignancy is variable with a 42% 5-year survival for stage C and metastases in 30% of cases (principally cervical nodes, bone and liver). The role of imaging is to define the criteria of a mass syndrome and to perform the preoperative staging in a case of apparently simple sinus obstruction. PMID- 1300092 TI - [Magnetic resonance imaging of neurofibromatoses]. AB - Neurofibromatosis is classified into two types. Type 1, NF1 or von Recklinghausen's disease, consists of skin and bone lesions as well as central nervous system tumours arising at the expense of glial tissue: optic tract gliomas, glioblastomas, astrocytomas and "hamartomas". Type 2 consists almost exclusively of CNS tumours arising at the expense of nerve envelopes: Schwannomas, meningiomas. PMID- 1300093 TI - [Unusual localization of a recurrent benign parotid tumor in the infratemporal fossa]. AB - Recurrences of parotid tumours are frequent (10 to 20% of cases) and require regular follow-up of these patients, especially when primary surgery was only partial and the initial tumour was multinodular. Malignant degeneration is reported in 1% of these tumours. The site of a parotid tumour in the infratemporal fossa is exceptional and usually indicates a malignant tumour metastasising along the internal maxillary artery and auriculotemporal nerve, as the inter-pterygoid aponeurosis is very resistant. However, this is no longer true following primary surgery in which damage to this aponeurosis is responsible for dissemination or localisation of the recurrence in the infratemporal fossa. The infiltrated appearance of the skin, muscles or fat is not suggestive of a malignant tumour and this dissemination can be explained by the multinodular and invasive potential of this tumour. PMID- 1300094 TI - [Atypical osteomyelitis of the base of the skull and malignant otitis externa]. AB - Osteomyelitis of the skull base is a rare, but serious disease whose incidence is tending to increase. It affects the marrow of the temporal, occipital and sphenoid bones and is generally secondary to Pseudomonas aeruginosa infection of the external auditory meatus. Based on a clinical case, the authors recall the difficulty of establishing the positive diagnosis and the possible confusion with neoplastic disease, hence the fundamental role of biopsies. They also review the literature on this subject. PMID- 1300095 TI - Dedication to Dr. Willem Johan Kolff. PMID- 1300096 TI - If we can do it, should we? PMID- 1300097 TI - The right to live in health versus the right to die in dignity. PMID- 1300098 TI - New approaches for cardiac assists: "back to the future". AB - The treatment of the modern epidemic of coronary artery disease requires the availability of various cardiac assist devices. A review and future implications of the use of retrograde coronary venous perfusion, the intraaortic balloon, a new ascending aortic pump, variable atrial septal defect, and novel energy sources are discussed. PMID- 1300099 TI - Is a totally implantable artificial heart realistic? AB - The incidence of local infection that occurred after the implantation of the intrathoracic Jarvik 7 total artificial heart (J-7 TAH) in patients was a major problem of this cardiac prosthesis. Infection rates increased when the J-7 TAH was implanted for longer periods of time, which was contrary to the results that were obtained by the implantation of the left ventricular assist devices (LVAD) either in the abdominal cavity or in the abdominal wall. Currently, the general belief is that the implantation of a cardiac prosthesis inside of the chest cavity is not safe, due to higher rates of infection. Thus, Part I of this paper deals with the question: "Is a total artificial heart physiologically acceptable?" We believe structural differences of the J-7 TAHs and other LVADs are an important part of the problem. The J-7 TAH is a volumetrically dynamic pump, and the other LVADs are a volumetrically fixed stationary pump. Based upon experiences of this investigator, intrathoracic implantation of a smooth surface pulsating device (or a volumetrically dynamic pump) generated persistent local inflammatory reactive tissues directly adjacent to the device. These tissue capsules were nonadherent to the device, and therefore may produce an ideal environment for allowing bacteria to grow. The findings were opposite to those for a non-pulsating surface pump inside the chest cavity. Part II of this paper discusses the question: "Is a totally implantable artificial heart technically achievable?" Many technical problems for the totally implantable TAH were already resolved during the development program of the totally implantable LVAD. However, there are three TAH specific problems that remain to be solved before achieving a clinically useful totally implantable TAH system. They are (a) anatomical compatibilities of the TAH system; (b) reliable control of the TAH system, (c) reliable and effective long-term operation of the TAH system. We have resolved the anatomical problem by the integral design of the pump-actuator system. Overall size of the hard shell Baylor TAH system is 510 cm3 with a diameter of 97 mm and a width of 82 mm. Its stoke volume was reduced to 63 cm3. The stable and reliable control of TAH performances was established by the three sets of Hall effect sensors with left master alternate mode of pumping. No physiological parameter was used as a feedback signal. Reliable long-term operation of the TAH system was established by the electromechanical actuation system. A simple drive mechanism with commercially available components and subsystems was used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1300100 TI - The mission of ISAO today and tomorrow. VIII World Congress of the International Society for Artificial Organs . August 19-23, 1991, Montreal, Canada. PMID- 1300101 TI - Multiple varieties of bionic support in kidney transplantation. PMID- 1300102 TI - Artificial and bioartificial replacement of the endocrine pancreas. PMID- 1300103 TI - Artificial liver support based on artificial cells with emphasis on encapsulated hepatocytes. AB - Artificial liver support requires more than a detoxification system. We have investigated additional approaches. Microencapsulated hepatocytes increased the survival time of fulminant hepatic failure (FHF) rats. They also lowered the bilirubin in Gunn rats. Xenograft of microencapsulated rat hepatocytes into mice are immunoisolated. The viability of hepatocyte increased from 62 to 100% after 29 days. This is because of accumulation of a hepatic stimulatory factor (> 100,000 D) secreted by the hepatocytes in the artificial cells. A novel two-step method of cell encapsulation greatly improved immunoisolation and biocompatibility. Other metabolic approaches included a multienzyme system for conversion of ammonia to essential amino acid, and removal of bilirubin. PMID- 1300104 TI - Intravascular oxygenator: a new alternative method for augmenting blood gas transfer in patients with acute respiratory failure. AB - A unique hollow fiber membrane oxygenator (IVOX) has been developed, which is inserted into the vena caval blood stream to transfer O2/CO2 to/from circulating blood in an intact subject without involving the natural lungs. Extensive laboratory testing has demonstrated that the device can transfer significant quantities of O2 and CO2 for up to 3 weeks without significant harmful sequelae or complications. Clinical trials are in progress under FDA supervision, in which IVOX has been utilized to date in 56 patients with ARDS. Preliminary findings indicate that risks and hazards from IVOX are nil, and evidence of benefit to the patient has been demonstrated in 86% of the patients. At this time, clinical utilization of IVOX is in the experimental, data collecting mode to determine its proper role or niche as a method for temporary augmentation of blood gas transfer in patients with advanced acute respiratory failure. PMID- 1300105 TI - Hematologic and hemostatic complications associated with long-term use of total artificial heart: clinical and experimental observations. AB - The two most serious complications associated with long-term use of a total artificial heart (TAH) are thromboembolism and infection. In this article, we review our experience in one patient implanted with a pneumatic TAH for 396 days, and in 24 calves implanted with the same type of device for 70 to 353 (median 150) days. During his survival with the TAH, our patient suffered several thromboembolic episodes despite adequate anti-coagulation with warfarin. Autopsy showed widespread thrombotic lesions, mostly in the brain. Throughout his survival, the patient had markedly elevated plasma beta-thromboglobulin and fibrinopeptide A levels, indicating sustained activation of platelets and the coagulation system secondary to blood contact with the artificial surface. Long term use of TAH in calves causes significant mechanical hemolytic anemia and a small reduction in the total leukocyte and neutrophil counts. The platelet count normalized to preimplantation levels by 25 to 35 weeks. At autopsy, thrombotic lesions and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. Although impressive gains in the clinical and experimental use of TAH were achieved during the last 15 years, thromboembolism and infection remain challenging problems. PMID- 1300106 TI - Rationing of uremia therapy. PMID- 1300107 TI - The economic load of the noncompliant patient: must society pay for the shrew? PMID- 1300108 TI - [Activities and isozymes of adenosine deaminase and lactate dehydrogenase in tuberculous pleural effusion with special reference to the presence of mycobacterium tuberculosis]. AB - We have previously shown that tuberculous pleurisy possesses a high level of adenosine deaminase (ADA) which is predominantly composed of ADA2. In this paper, we report the cases of tuberculous pleural effusion which contained mainly ADA1. In these cases, mycobacterium tuberculosis was positive by smear examination and/or culture and granulocytes were found to be major components. Analysis of lactate dehydrogenase (LDH) revealed that its activity was high and LDH5 occupied about 50% of total activity. In the tubercle bacillus negative cases, lymphocytes were the main components and the levels of LDH containing mostly LDH3 were low. It was assumed that the difference in LDH activity and isozyme pattern is due to the differential presence of leukocytes in pleurisy i.e., granulocytes and lymphocytes in tubercle bacillus positive and negative pleurisy, respectively. In conclusion, tuberculous pleural effusions can be divided into two groups on the basis of ADA and LDH activities and isozymes which may reflect the presence of mycobacterium tuberculosis. PMID- 1300109 TI - Antibiotic prophylaxis for prevention of bacterial endocarditis and infections of major joint prostheses [corrected]. AB - The current trend in antibiotic prophylaxis for prevention of endocarditis is toward more simple, effective regimens to promote better patient and dentist compliance. All national medical groups are now recommending oral regimens for all at-risk patients, and most of these groups recommend single-dose oral regimens. The Swiss Working Group recommends multiple-dose amoxicillin for high risk patients. The American Heart Association recommends two-dose oral regimens for all at-risk patients. Clindamycin appears to be the second drug of choice. The many pharmacokinetically different erythromycin preparations and the high rate of intolerance to many of these preparations has led to this change. No national or international medical groups recommended prophylaxis for patients with prosthetic joints. Most reviews conclude that there is little or no scientific evidence to support this use. It is time to stop the practice of prophylaxis for patients with prosthetic joints. The only patients with joint prostheses who should even be considered for prophylaxis are those patients considered at "high" risk. PMID- 1300110 TI - A full numerical solution to the problem of microelastohydrodynamic lubrication of a stationary compliant wavy layered surface firmly bonded to a rigid substrate with particular reference to human synovial joints. AB - A full numerical solution procedure has been developed for the microelastohydrodynamic lubrication analysis of a stationary compliant wavy layered surface firmly bonded to a rigid substrate. The results obtained have been compared with those using a simplified method adopted by Dowson and Jin(1) and good agreement has been obtained. PMID- 1300111 TI - A five-station hip joint simulator for wear rate studies. AB - The aim of the work has been the development of a hip joint simulator for comparative wear rate studies of long duration. A five-station apparatus has been designed, constructed and tested. Five total hip joints can be tested at the same time in identical conditions. The flexion-extension motion and the superior inferior component of the joint contact force are incorporated. The motion is electromechanical and the loading pneumatic. The angle and load waveforms are fixed and simulate level walking. For accurate wear measurements each station employs a control prosthesis. The conditions of the control prosthesis in regard to loading, exposure to lubricant and environment temperature (37 +/- 1 degree C) are identical to those of the test prosthesis. The acetabular cups can be readily removed for periodic wear measurements and reassembled in exactly the original position. Extensive tests have shown that the simulator is a practical and reliable instrument in the wear rate studies of various designs of total hip joint. PMID- 1300112 TI - A simulator study of friction in total replacement hip joints. AB - Frictional behaviour of 22 different femoral head-acetabular cup combinations was studied on a new servo-hydraulic microcomputer-controlled hip joint simulator using various flexion-extension angle and superior-inferior load set value waveforms and using distilled water at 37 +/- 1 degrees C as lubricant. Six different head materials were included in the study, whereas all cups were ultra high molecular weight polyethylene (UHMWPE). Most head-cup combinations studied are commercially available. No distinctly superior joint design can be pointed out, but the frictional behaviour of alumina ceramic against UHMWPE proved overall most favourable (mu min was 0.02), whereas that of non-ion-implanted titanium alloy Ti-6Al-4V against UHMWPE proved strikingly poor (mu max was 0.15). The lowest frictional torque was in 22 mm joints, but frictional torque did not always increase straightforwardly with increasing diameter of the femoral head. The measurements form an extensive comparison between a wide variety of head-cup combinations. The simulator is apparently a useful instrument in the study of frictional behaviour of new designs, materials, surface treatments and coatings that are frequently introduced. PMID- 1300113 TI - An approach to determining the kinematic parameters of biomechanical systems with applications to the wrist. AB - This paper presents an accurate and robust approach for determining the kinematic parameters of biomechanical systems. A computationally efficient algorithm is given for estimating the translation vector and rotation matrix of a moving body from measurements of the position of at least four spatially distributed points on the body. This algorithm provides an estimation of the spatial location and orientation of the body which is less sensitive to measurement error than other methods. It is indicated how the kinematic parameters can be used to determine the linear translation and angular rotation of the moving body in terms of an anatomically relevant coordinate system. The design, fabrication and calibration of an inexpensive, serial-link, three-dimensional mechanical digitizer for use in data acquisition is described. This device is kinematically optimized and is easy to use for accurate data collection. An implementation of this approach to quantifying certain aspects of the kinematics of the human wrist is discussed. PMID- 1300114 TI - Non-linear finite element analysis of formation and treatment of intervertebral disc herniae. AB - A biomechanical model of the spine motion segment L2/L3 consisting of the truncated vertebrae, endplates, intervertebral disc and pieces of anterior and posterior longitudinal ligaments has been used for a computer simulation study. A non-linear finite element analysis has shown that small loads compressing the spine, not greater than those occurring in everyday life, cause loss of stability of an intervertebral disc, resulting in lateral dislocation of its nucleus pulposus. This could be a potential cause of discopathy. The model indicates that conservative therapy of herniated disc by the traction method may result in retraction of hernia by about 40 per cent. PMID- 1300115 TI - Finite element stress and strain analysis of the bone surrounding a dental implant: effect of variations in bone modulus. AB - The long-term clinical performance of a dental implant is dependent upon the preservation of good quality bone surrounding the implant and a sound interface between the bone and the biomaterial. Good quality bone is itself dependent upon the appropriate level of bone remodelling necessary to maintain the bone density and the avoidance of bone microfracture and failure. Both processes are governed by the stress and strain distribution in the bone. In this study, a dental implant which had the same geometry as the Branemark system, but with a bioactive surface coating added to produce a direct bond to the bone, was analysed. A finite element stress and strain analysis has been carried out for a range of bone density distributions under axial and lateral loading. The predictions indicated that there was no evidence of strain shielding around the neck of the implant. With lateral loading, high values of von Mises stresses (18 M Pa) were predicted around the neck of the implant. A reduction in the elastic modulus of the bone around the neck of the implant by a factor of 16 only produced a twofold reduction in the peak stress. This resulted in stress levels capable of inducing fatigue failure in this much weaker bone. This analysis has demonstrated that it is extremely important to have good quality dense bone around the neck of the implant to withstand the predicted peak stresses of between 9 and 18 M Pa. Failure to achieve this after implantation and subsequent healing may result in local fatigue failure and resorption at the neck upon resumption of physiological loading. PMID- 1300116 TI - Engineering analysis of shoulder dystocia in the human birth process by the finite element method. AB - This paper presents an engineering analysis of shoulder dystocia (SD) in the human birth process which usually results in damaging the brachial plexus nerves and the humerus and/or clavicle bones of the baby. The goal is to study these injuries from the mechanical engineering point of view. Two separate finite element models of the neonatal neck and the clavicle bone have been simulated using eight-node three-dimensional elements and beam elements respectively. Simulated models have been analysed under suitable boundary conditions using the 'SAP80' finite element package. Finally, results obtained have been verified by comparing them with published clinical and experimental observations. PMID- 1300117 TI - Quality of the surface finish of the head of the femoral component and the wear rate of the socket in long-term results of the Charnley low-friction arthroplasty. PMID- 1300118 TI - Current approaches to new drug development in cancer chemotherapy. AB - This review summarizes and discusses current developments of new antitumor agents, with particular reference to mechanism of action, preclinical efficacy and interest for clinical evaluation. A progress is appreciable in the study of analogues of existing agents and in the identification of new series of cytotoxic compounds with a mechanism of action somewhat similar to that of conventional cytotoxic drugs. Advances in knowledge of tumor cell biology and biochemistry offer the prospect of identifying new targets for a selective drug action. The value of this new drug discovery approach remains to be established. PMID- 1300119 TI - Affinity and selectivity at M2 and M3 muscarinic receptor subtypes of cyclic and oxygenated analogues of 4-DAMP. PMID- 1300120 TI - Synthesis and pharmacological properties of 2-nitro-3-substituted-amino benzo(b)thiophenes and their 5-chloro derivatives. PMID- 1300121 TI - Cyclopentenyl ethylamines active on CNS. AB - Two new cyclopentenylethylamines were prepared and were submitted to a pharmacological screening together with some others previously described and now reprepared. All compounds exhibited different degrees of depressive activity on CNS and good analgesic activity. Compound 5, bearing a phenyl group on the carbon atom to which the amino group is connected, appears rather interesting being the most active as analgesic and the least toxic. Compounds 2 and 3 are able to antagonize in a certain degree lethal doses of physostigmine and also, respectively, of pentylenetetrazole and strychnine. PMID- 1300122 TI - Synthesis of N-substituted isocyanocarboxamides with antimicrobial activity. AB - The Ugi four-component condensation between isocyanides 1, cycloketones 2, and ammonium formate affords N-substituted formylaminocarboxamides 3 which are dehydrated with POCl3/NEt3 to give the title compounds 4. The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analyses. In vitro tests of antibacterial activity showed that compounds 4 are ineffective against E. coli and fairly active against K. pneumoniae, B. subtilis and S. aureus. A very good antimicotic activity was shown against C. albicans. PMID- 1300123 TI - Synthesis and in vitro activity of alkylaminoalkyloxy chromones on protoscoleces of Echinococcus multilocularis (Cestoda). AB - Twelve derivatives with alkylaminoalkyloxy chromone structures were synthesized and tested upon protoscoleces of Echinococcus multilocularis metacestode kept alive in vitro. Assays were performed with protoscoleces attached to the germinal layer in open and in closed vesicles. Compounds IVb and IIIe at the concentration of 0.1 mmol.L-1 killed 50% of the protoscoleces in open vesicles in 48 hours and compound IVb killed 100% of the protoscoleces in open vesicles within 96 hours at the same concentration. In closed vesicles after four days compound IVb killed all protoscoleces, compounds IIIe and IVd half of them, whereas in the controls all protoscoleces were alive. Trifluoperazine (TFP) was the reference compound; none of the new compounds showed better activity than TFP. PMID- 1300124 TI - N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines and their methyl esters: synthesis and antimicrobial activity. AB - The N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines (1-6) and the corresponding 5-carbomethoxy derivatives (7-12) were synthesized and characterized. Antimicrobial and antifungal activity was tested against Gram+ and Gram- bacteria and Fungi. PMID- 1300125 TI - On 9-amino derivatives of ellipticine and a comparative study on DNA apurinic site cleavage and mutagenicity. PMID- 1300126 TI - Formal potentials of new analogues of nifurtimox: relationship to activity. AB - Electrochemical studies (Formal Potentials and Coulometry) were performed on several analogues of Nifurtimox, in order to gain insight on the proposed mechanism of action of these drugs. It is thought that Nifurtimox shows part of its trypanocidal activity via an electron transfer process, leading to the production of active oxygen species that kill the parasite. Formal potentials provide relevant data about the feasibility of electron transfer in vivo. All analogues tested contained the nitro group, which is the most easily reducible group in the parent drug Nifurtimox. The formal potentials values determined ranged from -1.86 to -0.46 V. Coulometric runs were carried out to study the one electron transfer process. A good correlation between formal potentials and biological activity was found. PMID- 1300127 TI - Post-column derivatization and fluorimetric detection for the liquid chromatographic analysis of the potential memory-enhancing agent CL 275,838 in human plasma. AB - A chromatographic method for quantifying the potential memory-enhancing agent CL 275,838 (I) in human plasma with a limit of detection of 1.25 ng/ml is described. The procedure relies on isolation of the compounds from plasma constituents using the Sep-pack C18 cartridge, resolution by reverse-phase high pressure liquid chromatography (HPLC) and post-column oxidation of the eluate peak to from a derivative which can be measured by fluorescence detection. Peak height and compound I concentration were linearly related from 1.25 to 25 ng/ml. Intra- and inter-day validation studies indicated an acceptable precision and reproducibility of the method within the concentration range investigated, the overall coefficient of variation being less than 15%. PMID- 1300128 TI - Bioavailability study of furosemide prodrugs in rats. AB - According to the hydrolysis performance "in vitro" and lipophylicity, two Furosemide (F) prodrugs were chosen from a series of acyloxymethylesters of F synthesized previously: P1 (acetyloxymethyl-4-chloro-N-furfuryl-5 sulfamoylanthranilate ) and P4 (pivaloyloxymethyl-4-chloro-N-furfuryl-5 sulfamoylanthranilate+ ++). The bioavailability studies were assayed over two groups of eight male Wistar rats as a randomized two-way crossover and balanced design: group 1) a solution of P1 in propylenglycol/ethyl acetate vs an aqueous solution of F, and group 2) P1 vs. P4 solutions in oleic acid (P1#, P4#). These assays showed a better absorption performance of P1 and P4 than F, while the two prodrugs showed a similar bioavailability. The oleic acid seems to be responsible for the delay in the recovery of 50% of the total amount of F excreted in urine (T50%). When the monitoring is done in plasma after the administration of P1#, P1 was not detected as circulating prodrug. The analytical determinations of F in urine and plasma were done by high performance liquid chromatography (HPLC). From the urinary excretion data, a slope that indicates a slow elimination was found with a half-life of 12 hours approximately. PMID- 1300129 TI - Erosion. AB - With the current substantial decline in dental caries in adults, and increasing retention of teeth into old age, dental erosion is now being recognised as a major cause of tooth damage. It is easily recognised in its more advanced form, though more difficult to detect in its initial stages. Its mechanisms of action is generally not well understood. In this paper, current concepts of the chemistry of demineralisation of the mineral components of teeth are examined, with view to their providing a better understanding of some of the clinical characteristics of dental erosion of enamel. Categories and properties of potential erosive substances are reviewed. Speculation as to the potential effects of erosive substances on exposed root surfaces leads to consideration of the possible relationship between erosion and rapid caries development. The more commonly recommended mechanisms of control or prevention of erosion are described, and the rationale of their use analysed. PMID- 1300130 TI - Sleep and sleep disorders: an overview. AB - Sleep has been preserved during evolutionary history and is found in all mammalian species and birds. Despite the apparent strong survival advantage of sleep, and the observation in experimental animals that persistent sleep deprivation leads to rapid physical deterioration and death, the function of sleep is poorly understood. Modern neurophysiologic techniques have shown that sleep is not a homogeneous state but rather is divided into rapid eye movement and non-rapid eye movement stages. These two sleep states are as different from one another as sleep is from wakefulness. The advent of polysomnography has led to the recognition of a variety of sleep disorders; some, such as sleep apnoea, have potentially fatal consequences. Bruxism is an example of a parasomnia, viz a disorder which intrudes in normal sleep but does not lead to a primary sleep complaint. Recent improvements in diagnostic and therapeutic approaches to sleep disorders has led to the development of multidisciplinary Sleep Disorders Clinics. PMID- 1300131 TI - Determination of occlusal facial height in oral reconstructive procedures. AB - A review is provided of the methods that have been employed for the determination of occlusal facial height in oral reconstructive procedures. Details are provided in relation to a modified form of the patient's own assessment of a preferred vertical dimension of occlusion (PVDO) in dentate subjects exhibiting overclosure, edentulous subjects and in those patients requiring full mouth oral rehabilitation. PMID- 1300132 TI - The influence of modified cavity design and finishing techniques on the margin region of amalgam restorations: a simulated clinical study. AB - The use of high copper amalgams has substantially reduced the marginal fracture around amalgam restorations. Modified cavity designs and finishing techniques have been proposed for occlusal amalgam restorations in order to reduce further the long-term marginal fracture around these restorations. Clinical and laboratory studies are required before these techniques can be recommended to clinicians and taught to dental students with confidence. Using eighty extracted third molar teeth, this in vitro study examines four combinations of cavity design and finishing technique. After finishing, the restorations were photographed for evaluation of the initial marginal fracture attributable to the finishing technique, and sectioned twice to enable examination of the margin regions to determine the cavo-surface angles, amalgam margin angles and the occurrence of amalgam excess at and beyond the cavo-surface angle. Although careful application of the modified cavity design provided a mean cavo-surface angle of 100-110 degrees and assisted in achieving a mean amalgam margin angle of at least 70 degrees, long-term clinical and further laboratory studies are required before the cavity design modification can be recommended for routine use. PMID- 1300133 TI - To vent or not to vent? AB - The complete seating of full coronal restorations during cementation is hindered by the inability of cement to flow from the internal surface of the crown, and possible binding of the crown on the tooth. Perforation venting is an effective technique to allow full seating but requires repair of the perforation. Provision of space between the crown and the tooth for cement flow is also an effective technique, and does not require repair of a perforation. Such spacing is commonly achieved with die spacer, and has the added possibility of decreasing crown deformation during cementation by diminishing binding between the crown and the tooth. A disclosing agent is effective in aiding complete seating by identifying areas of binding. These areas can subsequently be adjusted, which will allow more complete seating. The placement of an appropriate amount of cement in the crown or on the preparation is an important addition to cementation technique. PMID- 1300134 TI - Restoration of a dentition affected by dentinogenesis imperfecta using In-Ceram: a case report. AB - A patient suffering from dentinogenesis imperfecta and consequent noncarious tooth destruction was rehabilitated using In-Ceram crowns. The problems encountered in the diagnosis, treatment planning and treatment are discussed. PMID- 1300135 TI - Prosthodontics--The Future? PMID- 1300136 TI - Abrasion: an evolutionary and clinical view. AB - Abrasion is the type of wear produced on the tooth by the friction of exogenous material forced over the surface by incisive, masticatory and grasping functions. It is one of the four common processes that have affected the morphology of newly erupted teeth from the time they first evolved millions of years ago. While some observers have regarded tooth reduction as pathological, there is evidence from comparative and palaeontological studies which demonstrates that these processes are an essential part of the normal, continually changing relationship between the form and function of the dentition. To understand these precise mechanisms is important if one is to replicate nature's 'intentions' in clinical dental procedures. PMID- 1300137 TI - The priming effect of ultraviolet B radiation on retinoic acid-stimulated collagen synthesis in the mouse photodamage model. AB - We have demonstrated previously that all-trans retinoic acid (tRA) stimulates collagen synthesis in ultraviolet B (UVB)-exposed but not in nonirradiated hairless mouse skin, suggesting that UVB exposure is required to prime certain tRA-induced events. The current study investigated further whether this tRA stimulatory effect on collagen synthesis could be regulated quantitatively by the accumulative dose of UVB. Mice were irradiated with the total amount of 0.25 (low), 0.77 (medium) or 1.43 J/cm2 (high) UVB radiation over 2, 5 and 10 weeks, respectively. Post-irradiation, 50 microliters of 0.1% tRA was applied topically 5 times a week. An initial delay was observed before tRA-induced collagen stimulation was detected in all 3 treatment groups. The first statistically significant increase in collagen synthesis was observed at the 6th week of tRA treatment in the high-UVB group. In the groups receiving medium and low UVB doses, onset occurred at the 8th week. Furthermore, at the end of tRA treatment, the degree of collagen stimulation correlated positively with the total UVB dose applied (increasing 183%, 224% and 250% over the vehicle control in the low-, medium- and high-UVB groups). By contrast, no collagen stimulation was detectable in the non-irradiated animals treated with tRA for 10 weeks, as previously reported. Although the mechanism by which UVB exposure primes skin to respond to tRA for collagen synthesis still remains unknown, the data indicate that the accumulative UVB dose positively affects the length of the initial delay and the magnitude of the stimulatory effect of tRA on collagen synthesis in photodamaged skin. PMID- 1300138 TI - Prediagnostic serum levels of 1,25-dihydroxyvitamin D and malignant melanoma. AB - A prospective nested case-control study of the relationship between prediagnostic serum levels of 1,25-dihydroxyvitamin D and subsequent development of malignant melanoma was done to test the hypothesis that increased levels are protective. Serum from 23 cases of malignant melanoma that developed between 1975 and 1987 in donors to the Washington County, Maryland serum bank was assayed along with that from 46 matched controls. There were no demonstrable differences among controls by sex, age, smoking or use of multivitamin supplements. The mean serum levels of 1,25-dihydroxyvitamin D were only 5% lower among cases than controls, a difference that could easily have occurred by chance. PMID- 1300139 TI - Photoprotective effects of sunscreens in cosmetics on sunburn and Langerhans cell photodamage. AB - It has become common practice to add sunscreening agents of variable potency to cosmetics to protect against the adverse effects of ultraviolet (UV) radiation exposure. The purpose of this study was to determine whether cosmetic preparations containing sunscreening agents protected against the adverse effects of acute UV radiation exposure and, if so, to identify the components responsible for the photoprotective effects. Pretreatment of skin with one such cosmetic product provided complete protection against UV-induced erythema, sunburn cell formation and Langerhans cell damage in volunteers, skin types II and III, whose skin was exposed to a 1.5 minimal erythema dose daily for 4 consecutive days. When individual components of the cosmetic preparation were analyzed for their photoprotective activities, it was found that both the cinnamate and benzophenone sunscreen combination and an extract of baker's yeast present in the preparation had photoprotective properties. These studies indicate that incorporation of photoprotective agents into cosmetic preparations provides a beneficial function and should therefore be encouraged. PMID- 1300140 TI - The biological interaction of cis- and trans-urocanic acid and DNA. AB - The potential for the cis and trans isomers of urocanic acid to produce DNA damage was measured by assays for DNA binding (32P-postlabeling assay), for induction of DNA repair (unscheduled DNA synthesis assay) and induction of mutations (Salmonella typhimurium and Escherichia coli plate-incorporation assays). These assays did not detect any evidence of a direct effect of either isomer of urocanic acid on DNA over a wide range of concentrations. These results suggest that neither isomer of urocanic acid alone, nor ultraviolet-irradiation of either cis or trans-urocanic acid produces significant DNA damage under conditions that permit cell survival. PMID- 1300141 TI - Urocanic acid isomers, immunosuppressive cytokines and the induction of human immunodeficiency virus. AB - The ability of cis-urocanic acid to mimic the effects of ultraviolet (UV) was tested in two systems that show cellular responses to direct UV irradiation. First, cultured mouse keratinocytes were treated with cis-urocanic acid and the cell culture supernatants were injected into mice to test for the ability to block spleen cell proliferation in the mixed lymphocyte reaction. Second, human fibroblasts carrying the chloramphenicol acetyltransferase gene under the control of the human immunodeficiency virus (HIV) long terminal repeat promoter were tested for the ability of cis-urocanic acid to induce gene expression. In these tests cis-urocanic acid did not induce a response comparable with UV irradiation alone, although at toxic concentrations cis-UCA did induce low expression from the viral promoter. These data suggest that, unlike UVB radiation, cis-urocanic acid does not activate keratinocytes to produce immunosuppressive cytokines nor does it induce expression of the HIV promoter. PMID- 1300142 TI - Experimental models for primary melanoma. AB - The nonmelanoma skin cancers squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) are by far the most common malignancies that occur in the United States each year. The third most common skin cancer, malignant melanomas (MM), accounted for 3% of all reportable cancers in the United States in 1991. The incidence of and mortality due to MM have been increasing at an alarming rate over at least the past 4 decades. As a result of this epidemic, there have been intense efforts to develop appropriate experimental models to examine the etiology and biology of this cancer. Benign and malignant melanocytic tumors have been produced in dogs, mice, guinea pigs, hamsters and gerbils with chemical carcinogens such as 7,12 dimethyl(a)benzanthracene (DMBA) and chemical promoters. Perhaps the most extensive and thorough studies using these chemicals were accomplished in the Weiser-Maple guinea pig model, in which radial and vertical stage growth occurred similar to human MM growth patterns. However, such stimuli are unlikely to be related to the human experience. Many investigators have considered ultraviolet radiation (UVR) from the sun to be intimately involved with the melanoma epidemic. Thus, a number of models have been developed to examine this possible relationship. These have included irradiation of DMBA induced benign melanocytic tumors in pigmented hairless mice, chemical promotion of UVR-induced tumors in haired mice and the induction of melanomas by UVR in the South American opossum. In addition, a melanocytic growth was produced with psoralens plus UVA in a haired mouse. All of these melanomas required chronic UVR exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300143 TI - Influence of age and sun exposure on the biophysical properties of the human skin: an in vivo study. AB - The physical properties of the skin were measured by using noninvasive methods on 72 people displaying various levels of solar elastosis on the neck. The physical parameters measured were the skin extensibility, the elastic recovery, the skin colour, the skin thickness and the electrical conductance. The correlation between the above parameters, the clinical grades of elastosis and the chronological age of each subject were studied using two different statistical approaches. They both showed that elastotic skin is less elastic, dryer, darker, more erythematous and less yellowish than the nonexposed skin. The similarities and differences between the properties of elastotic skin and purely chronologically aged skin are discussed. PMID- 1300144 TI - HSDM's five-year plan. Shaping the future of dentistry. PMID- 1300145 TI - Computer-assisted surgery. HSDM at forefront of revolutionary technology. PMID- 1300146 TI - Gallyas-Schiff stain for senile plaques. AB - Gallyas technique was modified by a direct application of Schiff's reagent after physical development, resulting in distinctive staining of amyloid deposits in argyrophilic structures. With this modified method, senile plaques in Alzheimer's disease are clearer. This method is easy to perform and suitable for routine neuropathological examination. PMID- 1300147 TI - Development of fern sporangia: a fluorescence microscopy study. AB - The utility of fluorescence microscopy for studying development of fern spores is investigated. Changes in the fluorescence characteristics during the developmental stages of fern sporangia can be attributed to the changes in the chemical composition of the cell wall. Bright blue autofluorescence of the spores indicated the presence of sporopollenin. The sporangial walls and the spores autofluoresced yellow under blue light excitation. Fluorescence microscopy is a useful addition to light, scanning, and transmission electron microscopy because living specimens can be studied owing to their fluorescence properties. PMID- 1300148 TI - In situ hybridization of plant meiotic and mitotic chromosomes: differences in signal detection. AB - The technique of in situ hybridization to both meiotic and mitotic chromosomes of Rumex acetosa is described. Differences in the efficiency of signal detection were observed between the two types of material. The implications of these results for in situ hybridization to other plant species are explored. PMID- 1300149 TI - Short fixation-shock freezing and freeze-drying versus chemical fixation and dehydration: computer assisted image analysis of morphological variables and immunogold labeling density on pituitary secretory granules. AB - We have performed a computer assisted image analysis evaluation of the effects of two preparation protocols on morphological variables and immunolabeling density of secretory granules using rat adenohypophysis as a model. Glutaraldehyde (GA) fixation for 2 hr and chemical dehydration was compared with short GA fixation (15 min) followed by cryofixation and freeze-drying (CF-FD). The 2 hr GA fixed specimens showed spherical nuclei and secretory granules regardless of their size, contrasting with the more irregularly shaped nuclei and secretory granules after short GA-CF-FD. In the latter group of specimens a correlation could be found between smaller nuclear areas and more irregular shapes. The differences in morphological variables between the two preparation protocols might be due to a better protein stabilization and a reduced collapse of macromolecules after the 2 hr GA fixation, strengthened by the chemical dehydration. The specific immunolabeling with antiserum to growth hormone was much greater but more varied after short time GA-CF-FD than after long GA fixation. Epon surface topography over the granule area also differed: smooth after short time GA-CF-FD and furrowed after long GA fixation. Our results, demonstrating important differences in morphological parameters and immunolabeling density between two common preparation protocols, seem critical for more reliable interpretation in quantitative immunoelectron microscopy. We also emphasize the need for computer assisted image analysis and measurements in immunoelectron microscopy to ensure objective evaluations. PMID- 1300150 TI - Bromodeoxyuridine immunohistochemistry for evaluating age-related changes in the rat mandibular condyle decalcified by intravenous infusion. AB - Age-related changes in cell proliferation kinetics of the mandibular condyle were studied in Sprague-Dawley rats using bromodeoxyuridine (BrdUrd) immunohistochemistry in decalcified, paraffin-embedded tissues. Intraperitoneal injection of 40 mg/kg BrdUrd was given 1 hr before animal sacrifice. Continuous perfusion of EDTA solution via the left ventricle shortened the decalcification time. Immunohistochemical staining was performed with monoclonal anti-BrdUrd antibody. BrdUrd labeled cells, i.e., the S-phase cells, were clearly visible with well-preserved cytological detail. Their nuclei exhibited homogeneously stained granules. The labeling index in the intermediate zone of the condyle decreased with increasing age of the animals. This method is useful for evaluating physiological and pathological changes of the rat mandibular condyle as well as other bones and joints. PMID- 1300151 TI - Calibration of quantitative histochemical methods: estimation of glycogen content of muscle fibers using the PAS reaction. AB - A fairly simple method for calibrating microdensitometric histochemical assays is described. The method is based on paired biochemical and histochemical assays on single freeze-dried skeletal muscle fibers which differ widely in their properties. As an example, the method is applied to investigate the validity of the periodic acid-Schiff (PAS) reaction for the microdensitometric estimation of glycogen content. Some problems that may interfere with the calibration are discussed. PMID- 1300152 TI - A method for thin sectioning heavily sclerotized cuticle of Odontotaenius disjunctus. AB - Elytra of the bessbeetle, Odontotaenius disjunctus were thin sectioned after embedding in epoxy resin. Sections were cut with a diamond saw, ground to the desired thickness on a rotary grinder and polished. Tearing and distortion were reduced when compared to knifecut sections of heavily sclerotized cuticle. PMID- 1300153 TI - A simple method for handling grids. AB - A simple method for handling electron microscope grids is described here. While assuring their identification and safety, this method provides improved handling, temporary storage, and identification of grids bearing ultra-thin sections, and in addition, provides a novel method for preparing bulk samples. Grids are attached at their edges to the weakly adhesive surface of a "Post-it" note pad which sits in a petri dish. The grids are safely immobilized on the pad, classified based on their location, and identified by convenient pad notation. Grid manipulation and identification are simplified using this device, which is easily assembled from readily available and inexpensive materials. PMID- 1300154 TI - Capillarity in rat skeletal muscle: effects of rapid freezing versus perfusion fixation. AB - We determined the effects of rapid freezing and perfusion fixation on fiber geometry and capillarity in rat skeletal muscle. Fiber areas were significantly decreased, and capillary densities significantly increased, in perfusion-fixed versus quick-frozen muscle. Significant differences in capillary-to-fiber ratios were not observed, suggesting that differences in fiber geometry, not the methods of quantifying capillaries, accounted for the differences in capillary density. We conclude that estimates of fiber geometry, capillarity, and diffusive gas conductances obtained from perfusion-fixed muscles are subject to significant error due to shrinkage. PMID- 1300155 TI - [Effects of stress on relative leukocyte frequency and serum sodium and potassium concentrations in bovines]. AB - The leucocyte and mineral profile changes were studied in bovines with different waiting time at the slaughterhouse. The stress induced by the waiting time at the slaughterhouse brought changes in relative leukocyte frequency, with inverted neutrophil:lymphocyte relation in animals with 24 hours of waiting time (1.45). However the sodium:potassium relation in the animals with 48 hours of waiting time was significantly lower (23.6, p < 0.001) than that almost normal in animals with 24 hours of waiting time (33.1). Also the high correlations between the parameters studied show an unique physiological or pathological situation. The found values point out hormonal changes similar to those in stress situations. PMID- 1300156 TI - Effects of post-training beta-endorphin and Met-enkephalin administration on two way active avoidance task in well-nourished and protein malnourished rats. AB - Protein malnutrition during suckling period or throughout the life affects the hypothalamic beta-endorphinergic system of adult rats. In the present study, rats were undernourished during suckling by feeding their dams an 8% casein diet whereas well-nourished dams received a 25% casein diet from birth until weaning (21 day of postnatal life). After weaning, the offsprings were maintained with the same diet as their dams. When rats were 3 month-old, they were subjected to two-way active avoidance task. Protein malnutrition did not affect the performance in the two-way active avoidance task. Post-training beta-endorphin or Met-enkephalin administration impaired the retention of shuttle avoidance task in both well-nourished and undernourished rats. However, the amnesic effect of the peptides was only achieved in undernourished rats with higher doses of opioids when compared to the well-nourished rats. These data suggest that undernourished rats present alterations in opioid sensitivity which may be related to changes in the levels of beta-endorphin previously observed both in brain and hypothalamus of early undernourished adult rats. PMID- 1300157 TI - Developmental changes in blood glucose and tissue carbohydrates in the fetal rat: effects of insulin and adrenaline. AB - The ontogeny of glucose regulation was studied in the rat by measuring the levels of plasma glucose, tissue glucose and tissue glycogen from fetal day 15 (E15) to adulthood. Since insulin and adrenaline are important glucose regulators in the adult, we also tested the effects of these hormones on above variables. The main findings are the following: 1) Umbilical blood glucose was very low (25 mg/100 ml) from E15 to E19, increasing to 66 mg/100 ml by E21 but still below maternal levels (110 mg/100 ml). 2) Umbilical venous-arterial (VEN-ART) glucose differences were very small (1 mg/100 ml) from E15 to E17, increased to 6 mg/100 ml by E19, but dropped again becoming negative (-15 mg/100 ml) just before birth when umbilical arterial blood glucose rose above venous blood glucose. 3) Glucose and glycogen concentrations rose drastically in liver towards the end of gestation. 4) Tissue glycogen and, to a much lesser degree, glucose, fell after birth to rise again in adulthood. 5) Insulin injection caused an increase in liver glycogen from E17 onwards, and also increased glycogen in brain and placenta on E19. However, insulin decreased glycogen in brain and kidney by E21. 6) Adrenaline caused an increase in the umbilical venous-arterial glucose difference at E15 and E17 with a concomitant increase in liver, brain and heart glycogen at E15. By E21 the response of liver glycogen to adrenaline was drastically reversed. Our data suggest that the mechanism regulating glucose homeostasis changes half way through fetal development. Tissue self-regulation is replaced with a centralized mechanism similar to that of the adult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300158 TI - Effect of lipoxygenase and cyclo-oxygenase inhibition on oleic acid-induced lung oedema. AB - The contribution of cyclo-oxygenase and 5-lipoxygenase metabolites on hemodynamics and oedema formation was investigated in 21 isolated rabbit lungs after a 10 min Oleic Acid (OA) infusion, by recording the changes on Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP). Lungs (n = 7) were pre treated with indomethacin (cyclo-oxygenase inhibitor) 50 min prior to OA or with Diethylcarbamazine (5-lipoxygenase inhibitor) (n = 7) or not pre-treated at all (control group, n = 7). The FFR in the indomethacin group was significantly greater than in the control and Diethylcarbamazine (DEC) groups 12 min after OA (7.6 +/- 2.3 mg.min-1 vs. 2.3 +/- 0.8 mg.min-1 and 0.96 +/- 0.8 mg.min-1 respectively) (P < 0.01). The FFR in the control lungs 20 min after OA was significantly greater than the corresponding DEC value (4.2 +/- 0.5 mg.min-1 vs. 1.6 +/- 1.0 mg.min-1) (P < 0.01). Mean Pulmonary Artery Pressure (MPAP) increased both in control and indomethacin groups (16.0 +/- 2.0 Torr to 24.3 +/- 3.7 Torr after 20 min OA and 14.4 +/- 2.5 Torr to 24.6 +/- 3.6 Torr at 10 min after OA, respectively), but MPAP value in DEC group did not significantly change 30 min after OA (14.7 +/- 1.5 Torr to 16.0 +/- 2.3 Torr) (P > 0.05). So we conclude that the selective inhibition of the 5-lipoxygenase metabolites (leukotriene-5hete) may play a protective role in OA induced oedema, whereas the selective inhibition of the cyclo-oxygenase pathway may have a deleterious effect on the hemodynamics and endothelial permeability in our experimental condition. PMID- 1300159 TI - [The posterior interosseous artery. Descriptive anatomy. Possibilities of clinical and orthopedic applications]. AB - Study of 25 forearms of fresh cadavers, whose the arteries have been injected with colored latex. The posterior interosseous artery is known for its superficial branches, which allow to autonomise cutaneous dorsal flaps. Its way, along the ulna allows to imagine other possibilities by use of the constant branches of this artery, which supplies the proximal and the distal extremities of the bone. The proximal branch is the posterior recurrent radial artery, which supplies the posterolateral face of the proximal pars of the diaphysis, in touch of the insertions of the supinator muscle, and the lateral edge of the olecranon. The distal arteries shape 2 or 3 fascicles, which disperse on the extremity of the diaphysis and the cervical pars of the ulna. To realize a vascular pedicle with the posterior interosseous artery, two cases can be envisaged: use of the distal ulnar epiphysis and creating of a direct pedicle. use of the proximal ulnar epiphysis and creating of a recurrent pedicle. PMID- 1300160 TI - [The intermetatarsal transverse ligaments and their connections with the tarsometatarsal articulations]. AB - The authors have performed 20 systematical dissections of the distal part of the foot, conserved in the Toulon's liquor and 3 dissections of fresh cadavers. The last ones have been submitted at different puttings in charge before and after the resection of the intermetatarsal transverse ligament. The intermetatarsal transverse ligament is supple, extensible, but very strong. It constitutes the area of convergence of all the neighbouring fibrous structures and of several tendons of the foot. It connects together the heads of the metatarsus. It renders them jointly liable and its action is reflected above. By its modulating of the convergence of the metatarsus and their necessary associated palmar inclination, by its limitation of their divergence in relation with their dorsal inclination, it modulates and it limits the amplitude of the tarsometatarsal joints. It is helped for that by the little intermetatarsal transverse ligaments, whose the presence has been always confirmed. The metatarsus varus, very frequently associated with the hall valgus, means the escape of the first ray from the effect of the transverse intermetatarsal ligament. PMID- 1300161 TI - [Extension of the fingers. III. Morphologic and structural study]. AB - The volar fascicles of the interosseous muscles possess two separate components: the proximal and glenoidal one, the distal and aponeurotic other. The armature of the dorsal aponeurosis is constituted the deep, the central and the collateral expansions of the extensor digitorum muscles, and the interosseous muscles, whom are added the lumbrical muscles. The deep expansions are constant and are fixed respectively at the basis of the first phalanx. The central and the collateral expansions constitute equally the central and the collateral, then terminal tendons, which are respectively fixed at the basis of the second and at the third phalanx. The unitive structures: dossiere, triangular and retinacular ligaments are intricate with this of the armature and render jointly the whole. All the concerned fascicles have the mechanical and histological characteristics of the tendon. PMID- 1300162 TI - [Extension of the fingers. IV. Morphologic and structural study]. AB - The putting in tension of the dorsal aponeurosis of the digits induces its retraction and the nearness of its insertions on the basis of the 3 phalanges. It depends on the extensor digitorum, interosseous and lumbrical muscles. The aponeurosis is not a single driving belt, but set off in itself 3 types of reaction: 1) The gliding on the sides of the pyramid, which constitute the proximal epiphyses of the phalanges. It suppresses the central dorsal-ward tensions. 2) The displacement of the axes of insertion and rotation of retinacular ligaments inducing collateral volar-ward tractions. 3) The modifications of the way of the structures of transmission: at one time the lengthening of the way is induced by the interactions of the fibers; at other times a shortening is suppressed by the extension of the close proximal joint. Analysis of the different fibrous and fascicular interactions and translations. PMID- 1300163 TI - [Extension of the fingers. V. Anatomic approach to lesions of the extensor apparatus]. AB - The physiopathology of the main deformities of the fingers, induced by the injury of the dorsal aponeurosis of the fingers, is caused by an imbalance of forces: proximally between extrinsic and intrinsic muscles; distally between central and collateral structures. The ulna Claw, caused by the whole paralysis of the intrinsic muscles, can be corrected by an interosseous tenodesis on the basis of the finger. The boutoniere is induced by the exaggeration of the action of the collateral structures with respect to this of the central structures. The swan neck is induced by the exaggeration of action of the central structures with respect to this of the collateral structures. The surgical treatment consist to give back those structures their normal lengthening and way, or else to create new detours or shortenings, allowing to give back the balance. So, any structures, spared by the traumatism, will not injure by the surgeon. PMID- 1300164 TI - [The bronchial arteries and their anastomoses with the coronary arteries]. AB - We studied bronchial arteries (BA) and their anastomoses with coronary arteries in 53 adult subjects (30 female and 23 male, mean age 82) and one 2 month old child. Each subject had 1 to 4 BAs, born from an area on the anterior side of the descending aorta measuring less than 2 cm in diameter in 62 percent of the cases and never exceeding 4 cm in the other cases. In 6 cases BAs vascularize the left auricle; more than half of all cases had an anastomose with the coronary arteries: 11 with the right coronary artery and 9 with the left one. These anastomoses preserve the vascularization of the carina after a cardio-pulmonary transplantation. The may have a function of vascular supply in some coronarian patients and the study of associated coronary pathology gives confirmation of it in one fourth of the cases. PMID- 1300165 TI - [Aspects of facial morphogenesis in the rat]. AB - The facial morphogenesis of the rat has been observed by scanning microscopy on embryos taken every day from the 10th post-coitum day to term. Three points should be noted. Firstly the muzzle has at the beginning of the development an individuality which tends to diminish later. Secondly the vibrissae, whose primary elements are grouped in plates, are of great importance in the development of the muzzle. Finally, the opening between the internal parts of the nasal ridges is elevated with at the top a sharp angle, contrary to that of man which is little elevated and is arched. This could express the difference relating in each of the two cases the mesenchymatous naso-dorsal center, to which divergence between the two types of face, one with muzzle and the other without, would be linked. The primates presenting these two types, the tendency at the moment is to classify them using this discrimination. The study of the two corresponding aspects would supply a precious addition to these observations. PMID- 1300166 TI - [Lymphatic drainage of the heart]. AB - The study was carried out on 91 adult cadavers to point out clearly the lymphatic drainages of the heart into the blood circulation. 45 right and 63 left ventricles and 9 right and 5 left atria were injected by means of a green modified gerota medium. A right collecting trunk received its afferents from 29 right and 5 left ventricles, ran upwards in front of the ascending aorta, involved the left brachiocephalic nodes and opened into the left subclavicular veins but also in 1 case in 5 into thoracic duct. A left collecting trunk received its afferents from 59 left and 23 right ventricles, ascended along the pulmonary trunk, involved the right paratracheal nodes and opened into the right subclavicular veins. From the right paratracheal nodes were also injected the left tracheobronchial nodes in 14 cases, and then the left brachiocephalic nodes twice, the left paratracheal nodes in 3 cases until the thoracic duct once and directly the thoracic duct in the mediastinum in one case. Afferents from the right atria ran upwards the superior vena cava and involved the right brachiocephalic nodes but connected also with the right paratracheal nodes as did the afferents of the left atria too. The connections with the thoracic duct must be emphasized. PMID- 1300167 TI - Type I familial amyloidotic polyneuropathy in Japan. AB - We studied 107 cases and 64 carriers of type I familial amyloidotic polyneuropathy (FAP) residing in 16 districts in Japan. The age of onset of illness ranged from 20 to 71 years old, with a mean of 40.1 +/- 12.8 years (SD). One quarter of the cases were late-onset patients who developed the disorder after age 50. Asymptomatic carriers older than age 50 accounted for 20% of total carriers, with the oldest carrier being a 94-year-old woman. All the patients had a variant transthyretin with a methionine-for-valine substitution at position 30 with a mean serum level of 9.78 +/- 3.27 (SD) mg/dl. The serum level did not significantly differ by gender in either patients or carriers, nor between patients and carriers. Incomplete penetrance of clinical expression was shown in eight cases. This study indicates that there is a considerable variety in age of onset, progression and geographic distribution of type I FAP in Japan. PMID- 1300168 TI - Paraneoplastic cerebellar degeneration: successful early detection and treatment of cancer through characterization of the anti-Purkinje cell antibody. AB - Paraneoplastic cerebellar degeneration (PCD) is thought to be caused by an autoantibody against both tumor and neuronal tissue. Such autoantibodies are most frequently detected in patients with gynecological or breast cancer, and are designated as anti-Yo. We report here a patient with PCD whose underlying cancer could not be detected despite extensive tumor survey. IgG in her serum and cerebrospinal fluid reacted with the cytoplasm of cerebellar Purkinje cells immunohistochemically. On immunoelectron microscopy, the endoplasmic reticulum and Golgi complex were stained. Her IgG bound to the 58 kD band on immunoblots of cerebellar proteins. A reaction was also observed with the recombinant proteins deduced from the complementary DNA clone encoding a neuronal cell antigen reported by Sakai et al (Ann Neurol 28: 692, 1990). Based on these results, successful early resection of fallopian tube adenocarcinoma was performed. It is crucially important to characterize these PCD related autoantibodies for the early treatment of underlying malignant tumors. PMID- 1300169 TI - Effect of interferon (IFN) on refractory idiopathic thrombocytopenic purpura: administration of 6 million units of recombinant IFN alpha-2b. AB - Five patients (six courses) with refractory idiopathic thrombocytopenic purpura (ITP) were given 6 million units of recombinant interferon (IFN) alpha-2b in 12 doses to achieve an improved response rate compared to previous studies using 3 million units. From the initial IFN administration, the platelet count increased from a pre-treatment level of 20.7 +/- 17.7 x 10(3)/microliters (mean +/- SD) and reached its first peak in weeks 2 or 3 of therapy (p < 0.05). In week 5, the platelet count made its second and maximum peak (66.5 +/- 57.9 x 10(3)/microliters; p < 0.05). A relatively good response of the platelet count (an increase to > 50 x 10(3)/microliters) was observed in three patients (four courses) out of five. These responses were not much faster or more improved than in previous reports, and a dose of 6 million units may be too large to treat some ITP patients. The platelet-associated IgG level showed a tendency to be reduced with IFN therapy. The mechanism for the increase of the platelet count may be the modification of platelet autoantibody production. PMID- 1300170 TI - A 72-year-old female with adult Still's disease. AB - We treated a 72-year-old woman with adult Still's disease. The diagnosis was made on the basis of a prolonged, high grade, quotidian fever, polyarthritis, maculopapular skin rashes and exclusion of other possible diseases. A high serum ferritin value was a key factor both in making the diagnosis and in the follow up. The patient responded to the administration of oral prednisolone at 30 mg/day, which was tapered to 10 mg/day, with no recurrence of symptoms. This disorder can be an important cause of prolonged fever in the elderly as well as in the younger population. PMID- 1300171 TI - Mixed connective tissue disease associated with protein losing enteropathy: successful treatment with intravenous cyclophosphamide therapy. AB - A patient with mixed connective tissue disease who developed protein losing enteropathy (PLE) is described. The PLE and other symptoms improved dramatically after monthly intravenous administration of 700 mg/day cyclophosphamide three times combined with oral prednisolone, while they were ineffective to the treatment with intravenous methyl-prednisolone 500 mg per day for 3 days. The serum level of CA125 antigen paralleled the severity of symptoms, signs and laboratory data associated with PLE. Thus, pleural effusion, ascites, edema and hypoalbuminemia improved along with the decrease in the level of CA125, suggesting that CA125 might be a marker of the activity of PLE. PMID- 1300172 TI - A rare case of extramedullary plasmacytoma in the mediastinum. AB - A rare case of extramedullary plasmacytoma in the mediastinum is reported. An 80 year-old man was admitted for further examination of a mediastinal tumor. Chest computed tomography (CT) revealed a large mediastinal mass and right interlobar pleural effusion. Needle biopsy under CT guidance established a diagnosis of plasmacytoma. Immunohistochemical staining revealed that the tumor cells were producing monoclonal IgA kappa. Serum immunoelectrophoresis revealed an IgA kappa monoclonal component with a serum concentration of 5,040 mg/ml. The bone marrow aspiration was normal. Bone roentgenogram and bone scintigram showed osteoporosis but no neoplastic lesion. PMID- 1300173 TI - Chondroid chordoma presenting with hypopituitarism. AB - A 28-year-old man with chondroid chordoma, an uncommon variant of chordoma, is reported. The patient presented with visual disturbance and hypopituitarism. The latter is a rare complication of intracranial chordoma. The preoperative diagnosis of chondroid chordoma of the skull base was based on unique findings on computed tomography and magnetic resonance imaging studies. The development of the tumor over six years suggests that the prognosis of chondroid chordoma may be poor in younger patients, as recently reported. Although chondroid chordoma is very rare, it should be included in the differential diagnosis of hypopituitarism. PMID- 1300174 TI - Mesenchymal hamartoma of the liver: report of an adult case and review of the literature. AB - A case of mesenchymal hamartoma of the liver incidentally found to be a hyperechoic mass by abdominal ultrasonography in a 62-year-old male is described. Computed tomography and magnetic resonance imaging of the liver confirmed the presence of a well-demarcated inhomogeneous mass in the left medial segment. Hepatic arteriography revealed the mass to be generally hypovascular. Histopathologic diagnosis of the resected specimen was a solid form of benign mesenchymal hamartoma, a rather rare lesion for the patient's age. Fifteen adult cases of hepatic mesenchymal hamartoma in the literature including the present case are reviewed. PMID- 1300175 TI - Disseminated intravascular coagulation in lupus erythematosus with acute liver damage. AB - A case of disseminated intravascular coagulation (DIC) in a patient with systemic lupus erythematosus (SLE) with acute liver dysfunction is described. A 37-year old man with SLE developed acute DIC and marked liver damage after fracture of the right clavicle and pharyngitis. Treatment with high-dose steroids, heparin, antithrombin III, gabexate mesilate, and antibiotics resulted in prompt improvement. The recovery of an SLE patient after acute DIC and marked liver damage is considered very rare. We report here such a case and discuss the previous reports. PMID- 1300176 TI - Primary extramedullary plasmacytoma of the lung. AB - A case with primary plasmacytoma of the lung is described. The patient, a 55-year old Japanese female, who simultaneously had a pulmonary plasmacytoma and bladder carcinoma. The bladder tumor was treated with transurethral resection. Pathologically, the bladder tumor was a non-invasive, papillary transitional cell carcinoma, grade II. The lung tumor was located in the right upper lobe and upper lobectomy was performed. The tumor measured 2.8 x 2.7 x 2.0 cm and had a white yellowish cut surface. Histologic, electron microscopic and immunohistochemical examinations of the lung tumor revealed monoclonal proliferation of plasma cells (IgA, lambda light chain). There was no evidence of multiple myeloma. PMID- 1300177 TI - Disseminated cryptococcosis presenting with adrenal insufficiency and meningitis: resistant to prolonged antifungal therapy but responding to bilateral adrenalectomy. AB - A case of disseminated cryptococcosis with features of primary adrenal insufficiency and meningitis in an immunocompetent host is presented. Despite antifungal chemotherapy, neither meningitis nor bilateral adrenal gland enlargement was improved. Aspiration biopsy of the adrenal gland revealed necrotic tissue with numerous fungi, suggesting that the adrenal glands were the focus of the persistent fungemia. Removal of bilateral adrenal glands led to improvement by making the patient more sensitive to antifungal chemotherapy. PMID- 1300178 TI - Locally invasive pulmonary aspergillosis in a healthy man successfully treated with oral fluconazole. AB - A 74-year-old healthy man with locally invasive form of pulmonary aspergillosis (PA) is reported. Chest X-ray film showed a segmental infiltration of right upper lobe (RUL) without cavitation, and the transbronchial lung biopsy specimen contained numerous hyphae of aspergillus species. Complication of bronchial asthma, or bronchiectasis were absent, and hyphae of aspergillus were present at only one segment of RUL. After 5 months of therapy with oral fluconazole, the PA had dramatically improved. Fluconazole was found to be effective for the locally invasive form of PA in a healthy man. PMID- 1300179 TI - Myoblast transfer in muscular dystrophy: panacea or pie in the sky? PMID- 1300180 TI - Mosaic expression of dystrophin in the cerebellum of heterozygote dystrophic (mdx) mice. AB - The monoclonal NCLDys1 revealed the presence of dystrophin in the Purkinje cells of normal mice but not of mdx mice and a mosaic staining in Purkinje cells of heterozygote mdx mice. Dystrophin was present in the soma and the dendrites of the dystrophin positive Purkinje cells and was absent in both regions of the dystrophin negative Purkinje cells. However, the polyclonal antibody d10 produced a uniform labeling of all Purkinje cells not only in the normal mice but also in mdx and heterozygote mdx mice. This staining was attributed to a reaction of this antibody not only with dystrophin but also with a different isoform of dystrophin or with a dystrophin related protein present even in mdx mice. PMID- 1300181 TI - Analysis of the tissue distribution and inheritance of heteroplasmic mitochondrial DNA point mutation by denaturing gradient gel electrophoresis in MERRF syndrome. AB - MERRF (Myoclonic Epilepsy and Ragged-Red Fibres) syndrome is one of the maternally inherited diseases for which a mitochondrial DNA (mtDNA) point mutation has recently been identified. The mutation is always heteroplasmic, that is normal and mutant mtDNA coexist within the same individual. We studied mtDNA heteroplasmy in two families with MERRF syndrome, using a denaturing gradient gel electrophoresis technique that avoids the errors in the evaluation of wild/mutant mtDNA ratios caused by restriction enzyme cutting in the situation of amplification of a heteroplasmic DNA. In two patients, the proportion of muscle mutant mtDNA was in agreement with the severity of muscle mitochondrial proliferation, energy defect and fibre type I predominance. In nine patients from three generations of one family, mutant mtDNA proportion in leukocytes was in relative agreement with the clinical severity of the disease. Transmission of mutant mtDNA through these three generations did not show any tendency toward homoplasmy. Homogeneity of the mutant mtDNA proportion among different tissues from one patient was demonstrated in brain, liver, muscle and heart but a possibility of divergence of the mutant mtDNA proportion during mitosis was documented in cultured skin fibroblasts. PMID- 1300182 TI - Experimental regeneration in canine muscular dystrophy--1. Immunocytochemical evaluation of dystrophin and beta-spectrin expression. AB - The expression of dystrophin and beta-spectrin was examined from 1 to 56 days in regenerating muscle fibres in normal and dystrophic dogs, following necrosis induced by the venom of Notechis scutatis. Normal and dystrophic dog muscle regenerated at an equal rate and new myotubes were present in both at the periphery of necrotic fibres by 3 days. In normal dogs dystrophin was detected in the sarcoplasm of the regenerating fibres by 3 days and was localized to the plasma membrane by 4 days. The localization of dystrophin is independent of beta spectrin and was detected before beta-spectrin, which was not observed until 5-6 days. Normal peripheral labelling of both was restored by 14 days in normal dogs. Normal beta-spectrin labelling of regenerating dystrophic fibres was also restored by 14 days and is not dependent on the presence of dystrophin in dystrophic dogs. A proportion of regenerating fibres in normal and dystrophic dogs showed weak immunolabelling of beta-spectrin prior to 14 days. This is a feature of immature muscle fibres. Antibodies to different domains of dystrophin bound to the periphery and sarcoplasm of regenerating fibres in dystrophic dogs, particularly during the first 7 days of regeneration, but the fluorescence was less intense than in normal dogs. Weak labelling with antibodies corresponding to the C-terminus of the rod domain of dystrophin persisted on dystrophic regenerating fibres up to 21 days. This may relate to developmental isoforms of dystrophin. PMID- 1300183 TI - Terminal intramuscular motor innervation and motor end-plates in thyrotoxic myopathy. AB - Thyrotoxic myopathy was induced in 64 mice. Examination of their muscles revealed excessive axonal branching and degenerative changes of preterminal axons. Moreover, the mean diameter of their end-plates decreased and the levels of end plate cholinesterase appeared to be reduced. In 43 patients with thyrotoxic myopathy, increased axonal branching and degenerative changes of preterminal axons, similar to those in the experimental mice, were also seen. The possibility that excess thyroid hormone may interfere with axonal transport or neuromuscular interactions is discussed. PMID- 1300184 TI - Age-dependent axonal loss in nerve biopsy of patients with xeroderma pigmentosum. AB - We describe the histomorphometric changes in the superficial peroneal nerve biopsy from 13 patients with xeroderma pigmentosum (XP). The mean age at time of biopsy was 15 yr (range 2.5-24 yr). The clinical examination was normal in the two youngest patients and showed absence of the deep tendon reflexes, with choreo athetosis in ten patients. In addition, in the three oldest patients there were cerebellar signs, ataxia and Babinski signs. The nerve biopsy showed an age dependent decrease of myelinated fibres, which was mild in the youngest and severe in the oldest patients. This was associated with rare acute axonal degeneration, sparse axonal regeneration, rare axonal atrophy and few onion bulb formations. These findings suggest a neuropathic process. This neuronal degeneration seems to be a progressive and stereotyped phenomenon in XP. PMID- 1300185 TI - Cognitive functions in Duchenne muscular dystrophy: a reappraisal and comparison with spinal muscular atrophy. AB - In order to clarify cognitive functions in Duchenne muscular dystrophy (DMD), we performed a new controlled neuropsychological study. IQ (WISC-R), verbal skills (fluency, confrontation naming and syntax comprehension) and memory abilities (BEM) were studied in two matched groups; 24 DMD children and 17 spinal muscular atrophy (SMA) children aged 12-16 yr. A significant difference appeared between the DMD and SMA patients: only in the DMD group were there significant disabilities in certain specific functions and normal scores in others. Despite similar education, the DMD children more often had significantly greater learning disabilities. There were more DMD left-handers. Verbal IQ was significantly low whereas performance IQ was at a normal level. DMD children also performed poorly in reading tasks and in some memory functions such as story recall and verbal recognition. Specific cognitive disabilities in certain DMD children, not seen in SMA children, suggest a relationship with a DMD genetic disorder. PMID- 1300186 TI - A randomized controlled trial of early surgery in Duchenne muscular dystrophy. AB - We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment. PMID- 1300187 TI - Chronic myopathy in a patient suspected of carrying two malignant hyperthermia susceptibility (MHS) mutations. AB - Malignant hyperthermia (MH) is a pharmacogenetic myopathy triggered by a variety of anaesthetic agents and muscle relaxants. In humans, susceptibility to MH is inherited as an autosomal dominant trait, and susceptible patients do not show a clinically relevant myopathy unless having suffered from a MH crisis. Homozygosity for the MHS trait is thought to be an uncommon finding, and so far only a few cases of patients suggested to be homozygous for MH on the basis of pedigree information were reported and described as having a more severe form of this condition resulting in clinical symptoms also in the absence of triggering agents. We report clinical findings in a patient with chronic myopathy beginning at the age of 2 yr and associated with a number of unique features, the most important being a family history of MHS present in both parents. She became symptomatic with marked muscular weakness and elevated serum CK levels. A muscle biopsy showed a distinct enlargement and increase of muscle mitochondria. In the in vitro contracture test the patient's muscle responded with unusually high contractures already at basal levels of triggering agents indicating a particularly severe MHS condition. DNA markers for the MHS1 locus, described previously on chromosome 19q12-13.2 in Irish and Canadian pedigrees, could not be used to confirm her homozygous state because our molecular genetic studies had previously excluded the MHS trait in this pedigree from this locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300189 TI - Unusual course of nemaline myopathy. AB - A boy with onset features common for a moderate form of congenital nemaline myopathy, after some years developed scapulo-humeral syndrome. Extra- and intrafusal muscle fibers overloaded with rods and indicating focal degenerative changes were seen in the first biopsy. The biopsy was later repeated and revealed an improvement in muscle architecture with a dramatically decreased number of rods. This transformation suggests that rods, as well as Z-line streaming, might be a reversible anomaly of Z-discs. PMID- 1300188 TI - Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy. AB - In this study we comparatively analysed deltoid histochemistry, biochemistry and mitochondrial DNA (mtDNA) in two groups of ten sporadic ocular mitochondrial myopathies (OMM), respectively with and without ragged red fibres (RRF). (1) All but one RRF--patients presented the mild form of OMM with blepharoptosis but without ophthalmoplegia; (2) the occurrence of cytochrome c oxidase deficient (COX-) fibres was significantly higher in the RRF+ group, but four RRF- cases also showed COX- fibres; (3) no difference was observed in biochemical findings between the groups; (4) two RRF- patients without COX- fibres showed mtDNA heteroplasmy; (5) in two RRF- patients without deltoid mtDNA deletion, biopsy of an eyelid muscle showed significant mitochondrial alterations. These results suggest that the expression of a mitochondrial defect can vary and that the absence of RRF in a skeletal muscle biopsy does not necessarily rule out the diagnosis of OMM, if other data support that. PMID- 1300190 TI - Polyglucosan body myopathy: a new case. AB - We report a 51-yr-old woman with late-onset progressive weakness affecting proximal limb muscles. Muscle biopsy revealed a vacuolar myopathy with accumulation of amylopectin-like polysaccharide resembling the polyglucosan found in type IV glycogenosis and adult-onset polyglucosan body disease. A biochemical study ruled out specific enzymatic defects known to cause storage of this abnormal material. Our case confirms the existence of a 'polyglucosan body myopathy' as a distinct clinicopathological entity in which the biochemical defect is unknown. PMID- 1300191 TI - International SMA consortium meeting. (26-28 June 1992, Bonn, Germany). PMID- 1300193 TI - Neuromuscular disorders: gene location. PMID- 1300192 TI - On chaos in classification of childhood spinal muscular atrophy. PMID- 1300194 TI - Synthesis and secretion of lipids by long-term cultures of female rat hepatocytes. AB - The objective of this work was to characterize lipid metabolism in long-term cultures of adult rat hepatocytes from female rats and explore the potential use of this culture system to study the effect of hormones, drugs and toxic chemicals on it. Hepatocytes, seeded on a feeder layer of 3T3 cells, maintained for 2 weeks their typical morphology. The cultures were able to take up [14C]acetic and [14C]oleic acid from the culture medium and incorporate them into lipids. The synthesis and secretion of lipids by [14C]acetic acid-labeled cultures had a maximum value after 11 and 13 days in culture. Triacylglycerols were the main lipidic species synthesized and secreted by hepatocytes (up to 67% of the total lipids); they also synthesized and secreted phospholipids, cholesterol and cholesterol esters from [14C]acetic acid. Similarly, [14C]oleic acid-labeled cultures synthesized and secreted mostly triacylglycerols (up to 60-70% of the total lipids), but they were also able to incorporate the labeled precursor into both cellular and secreted phospholipids and cholesterol esters. The activity of glycerol-phosphate-dehydrogenase, marker enzyme of glycerolipid synthesis, decreased slightly during the culture time whereas the activity of malic enzyme, marker of fatty acid synthesis, increased. Our results show that long-term cultures of female rat hepatocytes are able to synthesize and secrete several lipids, specially triacylglycerols, from both [14C]acetic and [14C]oleic acid for at least 2 weeks and that they maintain enzyme activities related with the synthetic pathways of glycerolipids and fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300195 TI - Segregation of viral double-stranded and single-stranded DNA molecules in nuclei of adenovirus infected cells as revealed by electron microscope in situ hybridization. AB - Formation of progeny viruses in the nuclei of HeLa cells infected with adenovirus type 5 was studied at the ultrastructural level by in situ hybridization techniques allowing specific detection of either viral double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA). Prior to the initiation of replication of viral genomes, infective DNA molecules which entered the nucleus of the target cell were randomly distributed among host chromatin fibers including nucleolus associated chromatin. They were double-stranded, that is, without single-strand breaks. Such association of viral DNA with host condensed chromatin also occurred in mitosis. The initiation of viral genome replication occurred simultaneously with the appearance in the nucleoplasm of small fibrillar regions containing intermingled viral dsDNA and ssDNA. Later, at the intermediate stage of nuclear transformation, viral dsDNA and ssDNA molecules were almost entirely separated into two contiguous substructures. At this stage, viruses were observed occasionally in the vicinity of viral ssDNA accumulation sites. Still later, an additional substructure developed in the centre of the nucleus which consisted of large quantities of viral dsDNA, traces of viral ssDNA and abundant viruses. Portions of viral ssDNA were attached to some viruses even at late stage of nuclear transformation, an association which strongly suggests the occurrence of encapsidation of at least some of the viral genomes while they are still engaged in replication. PMID- 1300196 TI - Drosophila C virus cycle during the development of two Drosophila melanogaster strains (Charolles and Champetieres) after larval contamination by food. AB - Drosophila C virus (DCV) cycle during Drosophila melanogaster development was studied after feeding contamination at the first, most sensitive, instar (L1). Two Drosophila strains were examined and compared. Presence of DCVC in apparently healthy animals (L3 larvae bred on a contaminated rearing medium and adults coming from larvae which were grown on medium containing DCVC) was demonstrated by biological tests. Using the immunofluorescence technique, DCV was exhibited in the diseased Charolles larvae, in the lumen of the digestive tract and in the basal part of gut cells which is in contact with the haemolymph. On the contrary, in Charolles larvae which seemed 'healthy', DCV was exhibited only in the lumen of the digestive tract at the apical boundary of the gut cells. But DCV typical protein capsid was not shown in the tissues of Drosophila L3 and adults. However, C virus remained in Drosophila tissues even after host metamorphosis and would seem to interact with Drosophila cells. Hypotheses are proposed concerning the intracellular state of Drosophila C virus in this case. PMID- 1300197 TI - Properties of chicken cardiac dystrophin. AB - We investigated the presence of dystrophin by immunoblot and immunofluorescence analyses, negative staining, rotatory shadowing and immunogold electron microscopy in chicken cardiac muscle. Saponin was found to be better than Triton X-100 for providing a new 'dystrophin-enriched' solution for use in biochemical studies of the molecule. By Western blot analysis, only a 400-kDa band was revealed with polyclonal antibodies directed against a central region (residues 1178-1723) of the dystrophin molecule and no cross-reactions with other proteins or degraded products were observed. Specific cleavage of the dystrophin molecule showed that the central rod-shaped domain corresponded to a resistant 'core'. This structure might rigidify the protein. By immunofluorescence, dystrophin was localized at the periphery of cardiac ventricular cells. The molecule was examined by electron microscopy and found to have variable lengths (140-160 nm for the monomeric from and about 260 +/- 10 nm or more for oligomeric forms). These oligomeric structures are considered to be associated molecules which are only partially overlapped lengthwise. The precise distribution of dystrophin within the cardiac muscle was determined by visualisation of gold particles in immuno-electron microscopy. Gold particles were found on the sarcolemma with no evidence of any association with cytoplasmic structures. The present data provide further details on the cardiac dystrophin molecule and suggest that its capacity of self-association may elasticize the dystrophin dimer. PMID- 1300198 TI - Immunodetection and localization of protein(s) related to retinal S-antigen (arrestin) in kidney. AB - S-antigen (arrestin) is a cytosolic protein which regulates phototransduction in retinal rods. A protein immunologically related to S-antigen was identified in fractions from soluble extract of bovine kidney enriched by gel filtration or by immunoaffinity chromatography using a polyclonal antibody to retinal S-antigen. On immunoblots, this protein was recognized by a panel of monoclonal antibodies (mAbs S2D2, S1A3 and S9E2) directed against different S-antigen epitopes and displayed the same apparent molecular mass (48 kDa) as retinal S-antigen. All three mAbs revealed a specific immunoreactivity by indirect immunocytochemical technique on rat kidney sections. The three mAbs recognized some but not all glomerular cells, identified as epithelial cells by immunoelectron microscopy using the mAb S9E2. Both mAbs S2D2 and S1A3 gave a diffuse cytoplasmic staining in all tubule cells. Proximal tubule cells exhibited a weak immunoreactivity, whereas distal and collecting tubule cells were strongly labeled. In contrast, the mAb S9E2 immunoreaction was restricted to a cell subpopulation from distal and collecting tubules corresponding to intercalated cells identified by immunoelectron microscopy. With the mAb S9E2, the labeling of proximal tubule cells was localized in the apical region of the cytoplasm. These results suggest that two or more 48-kDa proteins immunologically cross-reactive with retinal S antigen are present in kidney. The observed pattern of distribution is in keeping with the hypothesis that such proteins could play a role in the regulation of G protein-related receptors present in renal glomerulus and tubule epithelial cells. PMID- 1300199 TI - Developmental changes in the heterocellular epidermis of Pelobates syriacus integument. AB - Changes in characteristic components of the skin epidermis of the large tadpole of Pelobates syriacus were studied throughout its development. The fate of two specific cells in the skin epidermis was followed, from the young tadpole to the adult was studied. It was found that flask-shaped type cells in the tadpole epidermis which are PAS-positive, stain with peanut lectin (PNA). There is no detectable band 3 in the premetamorphosed stages, and mitochondria-rich cells are very rare. This pattern of staining changes completely upon metamorphosis: the PAS-positive cells, specific to the tadpole epidermis disappear, and the mitochondria-rich (MR) cells in the adult skin epithelium react with polyclonal anti-band 3 antibody. Western blot analysis showed the presence of a band 3-like protein of about 95 kDa, only in the adult epithelial extract, corroborating the immunocytochemical observations. The finding of the presence of band 3-like protein in the MR cells of Pelobates, is similar to the observations made in the skin of other amphibian species. On the other hand, the binding of peanut lectin to MR cells is species-specific, since it does not react with the MR cells in the skin epithelium of Pelobates syriacus. PMID- 1300200 TI - The European study of referrals from primary to secondary care. Concerned Action Committee of Health Services Research for the European Community. PMID- 1300201 TI - Planning primary care. "Towards even better primary care". A discussion document from: the Regional Primary Care Medical Advisory Committee of the South Western Region and the South Western Regional Health Authority. PMID- 1300202 TI - Sample size for a dose-response study. AB - This paper deals with a method of sample size allocation for a dose-response study assuming a logistic model for the dose-response curve. The method is based on the precision with which one wishes to estimate the dose that would produce the efficacy resulting in a clinically important difference from a placebo. An example is given to illustrate the methodology. The main development of the paper is for a binary response and is suitably modified for a continuous variable. PMID- 1300203 TI - A statistical test to assess changes in spontaneous behavior of rats observed with a computer pattern recognition system. AB - A computer pattern recognition system, RAPID, has been used to study the spontaneous motor activity of Sprague-Dawley rats. This system produces a large number of measures of the activity of control and experimental groups in any given study. The large number of measures involved presents a problem when one attempts to decide whether the behavioral activity of the exposed group differs from that of the control group. Extensive Monte Carlo studies have been performed in an attempt to develop and validate a simple statistic to be used in such decisions. PMID- 1300204 TI - Exploratory data analytic techniques to evaluate anticancer agents screened in a cell culture panel. AB - Information theory is used to provide a measure of selectivity, i.e., the degree to which a drug has preferential toxicity or growth inhibition for one or a few cell lines from a large panel. The selectivity measure is intended to complement a measure of differential growth inhibition in evaluating the drug development potential of a new compound. Also, a similarity measure obtained from information theory is used to classify drugs according to their pattern of responses on the panel. Some structure-activity relations emerge. This work is applied to 176 agents selected to be tested by the National Cancer Institute in about 50 cell lines. PMID- 1300205 TI - The analysis of a multiple-dose, combination-drug clinical trial using response surface methodology. AB - We consider the situation where a multiple-dose, combination-drug clinical trial is conducted to identify one or more combinations that satisfy regulatory requirements. Generally, these requirements involve a compound hypothesis with multiple comparisons. The min test has been shown to be an optimal alpha-level test for testing a single combination drug. Analysis procedures in a multiple dose, combination-drug study have typically involved classical ANOVA models or multiple regression models in a response surface methodology (RSM) framework. An inferential procedure based on an ANOVA model uses a screening test to address multiple comparison issues and multiple min tests to explicitly identify combinations satisfying regulatory requirements. An exploratory procedure based on RSM modeling is used to build a segmented linear model and a stairstep linear model to describe dose-response relationships. The two procedures are mutually supportive of one another in providing a broader assurance in the identification of effective combinations. PMID- 1300206 TI - A comparison of expiration dating period estimation methods. AB - Two methods of estimating expiration date have been compared. For a drug whose potency is expected to decrease with time, method 1 fits a linear regression line to the stability data, calculates a 95% lower confidence limit of the true degradation line, and estimates the expiration date by comparing the confidence limit with the lower specification limit. Method 2 calculates a 95% lower confidence limit b1 of the slope of the true degradation line, constructs a new line y" using b1 as its slope, and finally estimates the expiration date by comparing y" with the lower specification limit. In this work we show that in most practical situations, method 1 estimates greater expiration date than method 2. PMID- 1300207 TI - A comparison of linear and exponential models for drug expiry estimation. AB - While a large portion of pharmaceutical stability data is known to follow an exponential model decay, linear modeling of this data for expiry estimation is the norm. Expiry predictions based on linear and exponential fits to stability data were made to estimate the bias due to the linear fitting. It was found that within the usual expiry limits on drug potency, the difference between the model fits is relatively trivial. In cases of loss of potency greater than 15%, small assay variability, or great disparity between the length of the study and the time of expiry prediction, however, there is a nontrivial difference in the predictions and the exponential model is preferable. PMID- 1300208 TI - False alarm rates of statistical methods used in determining increased frequency of reports on adverse drug reaction. AB - Several statistical methods have been proposed or used in the determination of an increase in frequency of reports of adverse drug reactions. Some of the methods are based on large sample approximation or equal sample sizes assumption. The actual type I error may differ significantly from the predetermined nominal level of 5% when the methods are applied to rare adverse events. Simulated false alarm rates of the methods were compared under the assumption of 10 or less expected reports in the reference period. PMID- 1300209 TI - Statistical comparison of stability study designs. AB - Studies are routinely conducted during development of a new drug to investigate the effect of strength, package, batch, storage condition, and storage time on stability of the dosage form. A typical study will have three batches, several strengths, several packages, and several storage conditions. Thus, if every batch by strength by package combination is tested for every storage condition, i.e., if a complete factorial design is used, a substantial expense is involved. To reduce expense, a matrix design is commonly used; e.g., only the smallest and largest bottles are tested. Fractional factorial-type designs for stability studies are proposed, and the statistical powers of various designs are compared. PMID- 1300210 TI - Alternative approaches to the analysis of binary and categorical repeated measurements. AB - The purpose of this paper is to describe, illustrate, and compare a number of different approaches to the analysis of repeated binary and categorical data. These approaches include empirical generalized least squares and generalized estimating equations, as well as traditional log-linear modeling methods. It is shown that the interpretation of the parameters in the various models depends critically on the type of model fitted. In particular, we contrast the population averaged and subject-specific models. Two example data sets are used to illustrate the approaches, and throughout we concentrate on methods that can be easily implemented. PMID- 1300211 TI - General estimation of relative potency using prior information. AB - A general point and interval estimator of the log relative potency is exhibited in closed form, which incorporates prior information on the log relative potency for symmetrical as well as asymmetrical parallel line bioassay. The point estimator turns out to be a weighted average of the usual estimator and the prior mean where the weights are determined by the prior variance. PMID- 1300212 TI - Expanded confidence intervals, one-sided tests, and equivalence testing. AB - An argument, based on expanded confidence intervals, is given for always performing one-sided tests. However, if goals are not one-sided and "follow-up" inferences are required, then the usual two-sided confidence intervals (corresponding to two-sided tests) are generally appropriate. When equivalence testing is required (the goal being to show that treatments are "not too different"), expanded confidence intervals are more efficient than Westlake's symmetrical confidence intervals. PMID- 1300213 TI - Directional baseline differences and type I error probabilities in randomized clinical trials. AB - Adequate correction for baseline differences that occur in the same or opposite direction from inferred treatment effects in a simple randomized experimental design is addressed by Monte Carlo simulation. Results confirm that the analysis of covariance (ANOVA) can provide appropriate correction whether baseline means differ significantly by chance in the same or opposite direction from the inferred treatment effect. The results from analysis of simple pre-post difference scores are highly dependent on the direction of chance baseline deviations in relation to the directional treatment effect that would be inferred from rejection of the null hypothesis. The attempt to correct for baseline differences by expressing outcome as percentage of baseline entails directional bias that depends on the location of the zero point, the direction of change, and the level of correlation between baseline and follow-up measurements. PMID- 1300214 TI - Baseline correction in a two-way randomized blocks design. AB - Randomized blocks designs are used in clinical psychopharmacology research to test the hypothesis that relative effectiveness of different drug treatments depends on the type of patient being treated. Monte Carlo methods were used to evaluate the adequacies of different approaches to statistical control over baseline differences in such a design with special concern for the treatments x blocks interaction effect. Given the usual assumptions, analysis of covariance (ANCOVA) was shown to provide adequate baseline correction with consequent unbiased tests for the treatments x blocks interaction, as well as the main effect for the randomized treatments. Tests relying on simple pre-post difference scores and percentage change scores evidenced seriously conservative or nonconservative bias in the test for treatments x blocks interaction effect, a bias that depended on the direction of the corresponding interaction effect observed in the baseline measurements alone. This is discussed as a serious matter because the interaction effect in a randomized blocks design is a common basis for the claim of specific indications of drug treatments for particular types of patients. PMID- 1300215 TI - Demonstration of the reproducibility of treatment efficacy from a single multicenter trial. AB - According to the Food and Drug Administration's Guidelines for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, approval of a new drug "should be supported by more than one well-controlled trial and carried out by independent investigators. This interpretation is consistent with the general scientific demand for replicability." Nevius has described a four-point proposal for assessing statistical evidence in a single multicenter trial. Briefly, these four points are: (1) combined analysis shows significant results, (2) consistency over centers in terms of direction, (3) consistency over centers in terms of producing nominally significant results in centers with sufficient power, and (4) evidence of efficacy after adjustment for multiple comparisons. What is not clear from Nevius' proposal is how to quantify whether the amount of evidence in a single multicenter trial is equivalent to that from two separate trials. It is proposed that the post hoc subdivision of a multicenter trial may address this issue if the inherent multiple testing problem is accommodated. A minimax statistic is developed to test the hypothesis that the effect of the drug has been reproduced in a single multicenter trial. Monte Carlo simulation is used to generate the distribution of the minimax statistic under the null and several alternative hypotheses. Data from a multicenter trial are used to demonstrate the technique. Bootstrapping is used to determine the null distribution of the minimax statistic. PMID- 1300216 TI - On assessment of bioequivalence under a higher-order crossover design. AB - In bioavailability studies of two formulations of a drug, the standard two sequence, two-period crossover design is usually considered to assess bioequivalence. The standard two-sequence, two-period crossover design, however, may not be useful when differential carryover effects are present. In addition, it does not provide independent estimates of intrasubject variabilities for the two formulations. To overcome these problems, alternatively, a higher-order crossover design may be considered. In this paper, we derive statistical methods based on Schuirmann's two one-sided tests procedure for assessing bioequivalence for some commonly used higher-order crossover designs. Four designs, including Balaam's design, the two-sequence dual design, and two four-period designs (with two and four sequences), are considered. The relative merits of these designs as compared to the standard two-sequence, two-period design are discussed. Two examples concerning bioequivalence are used to illustrate the use of these methods. PMID- 1300217 TI - QCIS: a SAS-based relational database/query system for the Current Index to Statistics. AB - A portable, menu-driven software system for the Current Index to Statistics (CIS) cumulative database is described. The SAS-based system converts the CIS datafiles into a relational SAS database and provides windows for users to easily define their queries. Query execution may occur in batch or interactive mode. PMID- 1300218 TI - Computerized assessment in neuropsychology: a review of tests and test batteries. AB - This article contains detailed reviews of 13 computerized neuropsychological and performance test batteries and six stand-alone computer tests. Tasks found on these instruments are described and tables illustrate which batteries employ which measures. In addition to issues of reliability and validity, special considerations apply to computerized assessment. These issues are discussed and readers are provided information to help them assess computerized tests in relation to their particular clinical and research needs. Since many computerized tests were developed as performance assessment tools, the relationship between performance and neuropsychological assessment is examined. PMID- 1300221 TI - [Novel possibilities for treatment of parkinsonian tremor and other abnormal movements by stimulation of the nucleus ventralis intermedius thalami]. AB - Chronic thalamic stereotactic stimulation has been performed in 22 patients with disabling tremor and poor response to drug therapy: 17 parkinsonian tremors and 5 essential tremors. Our first results are presented with a mean follow-up of 26 months. Parkinsonian tremors 17 = complete disappearance: 12, clear improvement: 5. Essential tremors 5 = complete disappearance: 3, clear improvement: 1, failure 1 cured by thalamotomy. Choreic or ballistic dyskinesias 7 = complete disappearance: 5, clear improvements: 2. Dystonic dyskinesias 3 = complete disappearance: 2, failure: 1. This new stereotactic procedure permits to control easily not only tremor but also L-Dopa induced dyskinesias: choreic or ballistic dyskinesias and biphasic dystonic dyskinesias. The place of this surgical treatment among the other therapeutic possibilities is discussed. PMID- 1300222 TI - [Pseudomonas aeruginosa infection in cystic fibrosis: predominance of a single strain and the influence of antibiotic therapy and the environment]. AB - We analysed the implantation pattern and persistence of Pseudomonas aeruginosa in the tracheobronchial tracts of patients with cystic fibrosis, and investigated the relation of this bacterium with the environment and antibiotic therapy. We used four different techniques to ensure the precise and detailed identification of isolates. In particular, chromosomal differences were assessed by pulsed field electrophoresis (pulsotype determination). Sputum samples were collected from 8 patients, from 6 to 22 years-old, over a period of 19 to 24 months. Only a single strain was isolated from samples from each five patients taken at different times, and there was a predominant strain in the samples from two others. Patient 8, aged 14, was free of infection throughout the study. None of the infections was eradicated by antibiotic therapy (an association of two antibiotics for 15 days at one or two months interval). The strains isolated from two patients became resistant to imipenem: 3 out of the 4 resistant strains were the result of mutation in the resident, susceptible strain. Swabs were taken from the environments of infected patients and were tested for P. aeruginosa: this bacteria was found in three sites, and two of these contained an isolate with the same pulsotype as the strain responsible for the infection, whereas no P. aeruginosa was detected in the environment of an uninfected patient. The detailed and accurate identification of the isolates (by pulsotyping) enabled us--to show that each infected patient was infected by a single or predominant strain,--to investigate the relationship of these strains with those in the environment and the effects of antibiotic therapy. PMID- 1300223 TI - [Health education at school]. AB - The major health problems of our time cannot be solved only by the physicians. Despite important scientific advances, the number of cancers, cardiovascular diseases, bronchopathies and drug addictions increases. Prevention is a way of improving this alarming situation. Actually, the health of our contemporaries largely depends on themselves. For example, in a world without tobacco, one third of cancers and ninety per cent of lung and larynx tumors would not occur. Thus, the protections of human being's and nature's health are equally essential. Both are the State responsibility. Including hygiene in school education is a critical necessity in view of teaching young French students good health practices by which they will be impressed all their life. School has not only to teach but also to educate. This wish is in agreement with the Declaration of Child Rights voted by the General Assembly of United Nations on November 20, 1959. Unfortunately, the signatory nations do not put in practice this resolution which states that children must be protected against social risks. Descartes believed that "if the human species can be improved the means must be searched in medicine". This essential mission belong today to the educative system from home to school. At the dawn of the third millennium this "children institution", as Montaigne said, may provide health to future generations. PMID- 1300219 TI - Memory deficits in Alzheimer's patients: a comprehensive review. AB - Despite considerable experimental work on Alzheimer's disease (AD), the underlying cognitive mechanisms as well as the precise localization of neuropathological changes critical for memory loss remains undefined. A review of the neuropsychological literature on long-term memory deficits in AD patients suggests that AD patients display (a) a pervasive deficit of explicit memory, (b) a partial deficiency of implicit memory for verbal and visuoperceptual material (as measured by repetition priming procedures), and (c) a substantial sparing of implicit memory for visuomotor skills. The explicit memory loss is likely a result of encoding as well as consolidation difficulties. A faulty lexical semantic knowledge structure appears responsible for deficient repetition priming effects. Since neuropathological changes diffusely affect the brain of AD patients, establishing a clear relationship between localization of cerebral lesions and memory deficits is particularly difficult. Nevertheless, data suggest that extensive involvement of the hippocampal-amygdala complex plays a major role in explicit memory loss. Damage to associative cortical areas likely is involved in repetition priming deficits. The relative integrity of primary motor and sensory cortical areas and of the basal ganglia likely subsume, by contrast, the normal learning of visuomotor skills. PMID- 1300224 TI - [Secondary auditory risks from listening to portable digital compact disc players]. AB - The recent availability of portable high-performance digital disc-players in addition to cassette players, and with an increased dynamical range, has enhanced the risk to hearing for their users. The present study aimed at attempting to evaluate this hazard. After selection of a digital player, 12 normally-hearing voluntary subjects were exposed to listening to two records (classical music and hard-rock) at an acoustic level complying with safety regulations. Their temporary threshold shifts (TTS) were determined at 4 and 6 kHz just after exposure. The 0.5 kHz auditory thresholds were also measured as a control. At 4 and 6 kHz, the average value of TTS was 5 dB (standard deviation 3.1 to 5.9 dB). There was no statistically significant difference neither between the TTS at 4 and 6 kHz (p > > 0.05), not between TTS for the two types of music. A voluntary subject, suffering from a mild high-frequency hearing loss, was also tested. His TTSs were higher than average and may have corresponded to slower recovery (may be non monotonous). Therefore special caution should be recommended in such cases. The measurements have pointed out that very high acoustic levels could be reached (125 to 127 dBA) with a Leq (1 hour) od 110 dBAi.e. much higher than tolerable levels. Thus there is a serious risk to hearing, possibly increased by high level transients. Moreover, better headphones are likely to provoke TTS also above 8 kHz, which might be evaluated by high-frequency audiometry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300225 TI - [Humanitarian surgical missions]. AB - Humanitarian surgical missions are one of the most promoted aspects of french humanitarian action in the third world through the media. This action, previously limited, is now well-organised and its actors have become real professionals. The working conditions of this kind of surgery, are characterised by its lack of means and insecurity. Logistic, technical and ethic constraints have led to propose specific training suitable for these special conditions. PMID- 1300226 TI - [Human transmissible dementia: prion diseases?]. AB - Subacute transmissible spongiform encephalopathies (STSE) represent a cause of presenile dementias, found in man (Creutzfeldt-Jakob disease, Gerstmann Straussler syndrome, Kuru), in sheep and goats (scrapie), in cattle (bovine spongiform encephalopathy) and in various mammals. It seems that the frequency of the human spongiform encephalopathy (HSE) is more frequent than thought up to now and an alimentary origin is not to be discarded. Many discussions are held concerning the nature of the transmissible agent: virus, virino, prion? Isolation of an abnormal protein, the isoform PrPSc resulting from an unknown alteration of a protein PrPc encoded in man by the chromosome 20 is presently the basis for seeking the cause of transmissible dementias. Molecular genetic studies of the gene PrP have demonstrated the existence of many mutations: are they the actual cause of the STSE or only a favouring factor? The existence of familial sporadic or infectious forms of HSE might be explained by alterations of the conformation of PrPc into PrPSc, able to induce this structure modification to last when thereafter the synthesis of the normal protein is achieved. The "chaperone" protein model can be questioned in this respect. For the moment the research work is developed into characterization of humoral or genetic markers able to detect the predisposed subjects in high-risk families. HSE are also an interesting model for other types of dementias, especially the Alzheimer disease which is still the preferred target of research in this field. PMID- 1300227 TI - [Genetic engineering in plants]. AB - Until recent years, plant genetic was involved in heredity studies through the analysis of segregations in progenies after crossing. New potentiality arose as genetic tools with the use of dissociated plant elements, transforming and cultivating them in vitro. When plants are regenerated from manipulated tissues, new structures of varieties (clones) new genotypes (transgenic plants) and new regulations of genes expression (vitrovariants) open new ways for plant genetic engineering. Progressively these technological tools are integrated in the methods of plant breeding. Yet all possible consequences of these new types of heredity and of these new genetic structures must be evaluated. As first priority the analysis of possible incidences in the field of food, nutrition and health gives the basis for diagnostics and organisations aiming to avoid the release of genotypes which could have unwanted effects. PMID- 1300220 TI - Is anorexia nervosa a neuropsychological disease? AB - Evidence for central nervous system, and more particularly cortical, etiology of anorexia nervosa is reviewed. Topics covered are neuropsychiatric comorbidity, inheritance patterns, the neurobiology of body-image disturbance and of the eating function, perinatal and alcoholic insult to the brain, neurochemical and neuroelectric disturbance, anatomic and metabolic brain imaging, and neuropsychological impairment. It is concluded that there is indeed an important neuropsychological etiological dimension to anorexia nervosa. The profile most frequently associated with anorexia nervosa is right posterior hypometabolism, followed by right anterior hypermetabolism, both associated with right-sided abnormal electroencephalogram spiking. It is also proposed that bulimia consists of a "positive" neurological subtype and that restricting anorexia represents a "negative" neurological subtype. Priorities for further research into anorexia nervosa are specified to include twin adoption studies, brain electrical topography studies, postmortem histological studies, and experimentally inspired neuropsychological studies. PMID- 1300228 TI - [Current trends in the field of animal husbandry]. AB - The progress achieved over the past 30 years in the areas of nutrition, physiology, genetics and prophylaxis has lead to the intensification of animal production. Feed additives have been one of the factors involved in this evolution often wrongly accused of being at the origin of a so-say degradation of the quality of the products. Where nutritional quality is concerned, it must be observed that the genetic determinism and the homeostasis of the organisms maintain practically constant the proportions of the elementary constituents (amino acids, fatty acids) and the composition of the basic components (proteins, phospholipids) of the living matter. However, the relative proportions of these components (proteins/lipids) can be modified by genetic and nutritional factors. If the quantitative modifications of composition are easily balanced by the diversity of the human diet, they can heavily influence the technological and organoleptic properties of the individual animal products. The on-going evolution, namely the incidence of the new biotechnologies, should not modify this situation, if only to lead to the production of animals whose tissue and product composition would be adapted to the technological and dietetics demand. The nutritional balance should then be assumed by a better educated and informed consumer. PMID- 1300229 TI - [Biotechnology using modified microorganisms]. AB - Few microorganisms, as compare to their high diversity, are used for human needs. They can produce molecules of interest, process fermentation, protect crops, treat wastes or clean environment. Molecular technics and genetic engineering are new tools offer to geneticists which breed microorganisms for years. Using them, it is now possible, theoretically, to introduce any gene in any organism. Some examples are given concerning genetic modifications in yeasts and lactic acid bacteria to optimize agrofood processes and to improve nutritive and flavour characteristics of fermented products like bread, beer, wine, cheese, meat, vegetable juices... In spite of scientific and industrial interest of the new technologies, limiting factors can explain that genetically modified microorganisms are not routinely used in agrofood yet. First, risks assessment on human health and environment are still in debate, but their is a consensus, within the scientific community, to consider that new characteristics of improved microorganisms are more important than the technics used for their construction. Second, regulations turn out to impose constraints susceptible to discourage technological innovations. At least, the public perception about the new technologies appears, actually, as the major factor to limit their development. PMID- 1300231 TI - [Novel technologies in the food and agriculture industry]. AB - Product innovation obtained by means of new processes or novel raw materials or ingredients is not a recent event. The consumer today has access to a large array of products from which he may compose a nutritionally balanced diet with no inherent questions regarding food safety or wholesomeness. The controversial opinions of the consumer with regard to certain new technologies applied to food should not be confounded with the possible existence of a related unacceptable risk of the corresponding products. Scientific knowledge, from which such technologies are the result, provides a solid basis for the establishment of food safety. The principle of risk assessment should be applied by the manufacturer whenever innovative technologies are introduced in the creation of new food products. PMID- 1300230 TI - [Ionization]. AB - Having demonstrated the wholesomeness of irradiated food, then scientists had to prove that nutritional impact of food irradiation was minor. Animal testing, vitamin and amino acid measurements in irradiated food, and no longer in solutions, have demonstrated that recorded changes, at commercial doses i.e. 1 to 10 kGy did not present any hazard. It must be noted that sensory qualities of radiosensitive food products like milk, are altered well before nutriments. PMID- 1300232 TI - [Methods of evaluation]. PMID- 1300233 TI - [The control of foodstuffs at the beginning of 1993]. AB - The 1st January 1993 the frontiers between the Member States of the European Community and the customs controls will disappear. The abolition of this type of control won't affect the food security. The french administration has strong legal rules to ensure the protection of consumer's health. The regulations prepared by European Community in order to allow the free circulation of goods also ensure a high level of consumer's protection. In case of harmonization, each Member state keeps some rights when there are risks for consumer's health. In absence of community regulations the principal of mutual acknowledgement aiming to avoid the barriers to trade can then not be applied for health and security necessities. The authorities controls are now resolutely inserted in an european context: priority to controls during production, harmonized methods of intervention to promote the required acknowledgement of controls enforced in each Member state, involvement in an european alert system, and development of the cooperation between the national administrative authorities of inspection. Regarding the matter of food security the authorities need the assistance of the scientific community and of its national and international representative organisations. They take an essential part in diagnosing, emergency and advice during the elaboration of regulations. Their power should be even greater with the implementation of the european scientific cooperation. PMID- 1300234 TI - Stable triple helices are formed upon binding of RNA oligonucleotides and their 2'-O-methyl derivatives to double-helical DNA. AB - Pyrimidine oligoribonucleotides bind to the major groove of double-helical DNA at homopurine.homopyrimidine sequences. They recognize Watson-Crick base pairs by forming T.A x U and C.G x C base triplets via Hoogsteen hydrogen bonding. The stability of these triple helices is much higher than that of triple helices formed by oligodeoxyribonucleotides as shown by an increase of the temperature at which half-dissociation of the third strand occurs. When the 2'-hydroxyl group of ribose moieties is replaced by 2'-O-methyl substituent, triple helix stability is further increased. PMID- 1300235 TI - [Is the centrosome a dynamic structure?]. AB - Ca++ effects on the organization of human centrosomes isolated according to Bornens et al., were followed by double immunofluorescence technique. Ca++, at millimolar range, is able to modify the distribution of the pericentriolar material (PCM) and to decrease the intercentriolar distance. In the light of these results, we have slightly modified the centrosome isolation method and shown that centrosomes isolated in the absence of EDTA have several structural differences from the previously described structure. In particular, centriole diameter is decreased by a transverse sliding of microtubule triplets with respect to each other, suggesting the possibility of movements within centrioles themselves. PMID- 1300236 TI - TAP1 and TAP2 transporter genes and predisposition to insulin dependent diabetes mellitus. AB - Genetic control of insulin dependent diabetes mellitus (IDDM) is mainly dependent on HLA genes in the major histocompatibility complex (MHC). The participation of TAP1 and TAP2 genes, located in the MHC region and coding for antigenic peptide transporters, was investigated in 116 IDDM patients and 98 normal controls using oligotyping after DNA amplification. The TAP2-B allele had a dominant protective effect, additive to that of the DR2 haplotype but antagonist to the susceptibility associated with the DR3 and/or DR4 haplotypes. The TAP2-A allele, in the homozygous state, had a predisposing effect. TAP1 allelic distribution did not differ among IDDM patients and controls. These data argue in favour of the role of peptide transporter gene in diabetogenesis. PMID- 1300237 TI - [Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies]. AB - Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity. PMID- 1300238 TI - [Management or strategy within hospitals]. AB - A study was conducted on certain number of hospital departments to identify the kind of variables which determine decision-making and decision-implementation as concerns innovations, both in medical process and hospital organization. Among the internal variables, one can quote the size of the hospital, its ownership type, its main field of activity, its situation in the local health structure, its resources ... Among the external variables one can quote the supply of care at the local level, the local health networking, the state of technological development, interrelationship of the health sector, the manufacturing sector and the research sector, the presence of managerial tools and skills... PMID- 1300239 TI - [Hospital costs: results of empirical studies]. AB - The DRG hospital payment system will be introduced in France in 1993-94 under the name of GHM ("groupes homogenes de malades"). However the method for evaluating costs is mainly based on past trends and, as a matter of fact, they exclude innovative care behavior from the doctors. Three new methods are therefore experimented: (i) standardized operation protocols; (ii) observation of consumed products and time of health personnel; (iii) observation of the costs resulting from the tariffs of the Social Security administration. The empirical studies were carried out in Montpellier and Nantes, two middle size cities of France. PMID- 1300240 TI - [Road violence among young people aged 15-24 years]. AB - During the last decade, the annual number of deaths by road accident in France was approximatively 10,000 whose 3,000 aged 15-24. Road accidents were, and remain, the first cause of death among youngsters and young adults, preceding suicide. Since the early 70's, public authorities were aware of the problem and laws and regulations were implemented, aimed at curbing the disastrous trend. Some results were obtained, but the situation is far from satisfactory. Social, economic, psychological conditions of modern society are favouring road violence, which is today among the most acute public health issues, as far as the young are concerned. Road accidents vary according to the age of the young. Moreover, its rate varies according to the region within the country. PMID- 1300241 TI - [Econometric and ethical validation of regression logistics. Reducing of the number of patients in the evaluation of mortality]. AB - In general, a large number of patients is needed to conclude whether the results of a therapeutic strategy are significant or not. One can lower this number with a logit. The method has been proposed in an article published recently (Cost utility analysis of early thrombolytic therapy, Pharmaco Economics, 1992). The present article is an essay aimed at validating the method, both from the econometric and ethical points of view. PMID- 1300242 TI - [Application of Bayes discriminatory analysis to malaria stratification in Hainan province]. AB - The present study was conducted to explore a new method for stratification of malaria endemicity. Several socioeconomic and geographic factors deemed appropriate to be employed in association with malaria epidemic potential were deal with Bayes discriminatory analysis.55 local villages in 12 counties of Hainan province were selected for socioeconomic survey, among which 33 villages were taken as the modelling sample and 22 villages were the non-modelling sample. The questionnaire contained a total of 12 relevant items. After socioeconomic inquiry was performed, the data were analysed through Bayes discriminatory theorem. Six important factors ware selected, i.e. topography (X1), proportion of labour forces (X4), income per person (X5), house structure (X8), knowledge of malaria control (X10), frequency of over-night stay in mountain forest (X12). Three discriminatory function formulas referring respectively to hyper-, meso-, and hypo-endemicity were set up. These 3 discriminatory function formulas were further applied to fit the endemicity of 33 model-sampling villages and 22 non model-sampling villages. The agreement rate were 91.0% and 77.3% respectively. PMID- 1300243 TI - [An epidemiological investigation of outbreak of measles among temporarily living people in Shenyang]. AB - This paper reported an outbreak of measles occurred in a factory of Heping District in Shenyang in March 1989. All of the six diagnosed cases were temporarily workers, which represented 15 percent (6/40) of total workers. No secondary cases were detected. The results of epidemiological and laboratory analysis showed that this outbreak was caused by an imported case, and only spread in temporarily workers. Furthermore, we discussed that under the condition that measles incidence was limited under control level, even imported cases could not cause epidemic of measles. So, it is indicated that the flowing people can easily cause accumulation of susceptible people in cities, which may result in outbreak of some infectious diseases. PMID- 1300244 TI - [Survey on tick vectors of Lyme disease spirochetes in China]. AB - Since 1987 we have been studying on Lyme disease in China. There were 71 isolates of Borrelia burgdorferi recovered from six species of ticks including Ixodes persulcatus, Ixodes granulatus, ixodes rangtangensis, Haemaphysalis concinna. Haemaphysalis bispinosa and Haemaphysalis longicornis, and 55 isolates from Ixodes persulcatus collected from Heilongjiang, Jilin, Liaoning, Nei-Monggol, Hebei and Xinjiang region (province). Ixodes persulcarus is the dominant species accounted for more than 80% of the total number of collected ticks, 20 or 45 per cent adult Ixodes persulcatus contained spirochetes as determined by direct immunofluorescence in the northeast and northwest. The seasonal change of adult Ixodes persulcatus is coincident with that of the patient with Erythema migrant. These studies proved that Ixodes persulcatus play the leading role in transmission of Borrelia burgdorferi to human in north region of China. It is not clear what species of tick is the principle vector in the south region of China, though the spirochetal isolates were cultivated from Haemaphysalis bispinosa, Ixodes granulatus and Ixodes rangtangensis. Comparison between Chinese strains of spirochetes from ticks and American strain B31 in Ultrastructure, monoclonal antibodies reaction and outer surface protein profile revealed certain differences. PMID- 1300245 TI - [A case-control study on the transmission factor of hepatitis A outbreak of Wenzhou in 1988]. AB - This investigation described a pair-matched case-control study on transmission factors of hepatitis A outbreak in Wenzhou City in earlier 1988. The results during early stage of the epidemic showed that, for the people having had meal in eating houses OR was 9.08, whereas for those having eaten clams OR was 3.63. The results during middle and later stages showed that, for the contactor of hepatitis A patients OR was 5.02, while for those having eaten clams OR was 4.29. The result of this investigation showed that this outbreak was related to eating in eating houses during the early stage of the epidemic, but related to both contact with HA patients and eating clams during middle and later stages of the epidemic. PMID- 1300246 TI - [Immune response to hepatitis B revaccination in children]. AB - In this report, we investigated the efficacy of revaccination with hepatitis B vaccine in thirty-eight children after primary immunization. The results showed that anti-HBs immune response developed in 37 children after revaccination. with a response rate of 97.4% (37/38). The geometric mean titres (GMTs) of anti-HBs at 3rd weeks, 3rd and 6th month after the booster dose reached 824.1, 407.7 and 193.6IU/L, which were 24.5, 12.1 and 5.8 times higher than those before the booster dose (33.6IU/L), respectively. The peak levels reached at 3rd week after revaccination. However anti-HBs levels declined rapidly, the percentage of antibody decrease were 50.5%, 76.5% at 3rd and 6th month after booster dose respectively. The immune response to revaccination gave a strong correlation to the primary immunization. In conclusion, our findings indicated that a good response to revaccination with a dose of 10 micrograms of hepatitis B vaccine in children were observed. PMID- 1300247 TI - [Detection of Toxoplasma antibody among pregnant women and newborns in Jingmen]. AB - 748 sera from lying-in women and newborns were tested for anti-toxoplasma antibody with the method of IHA. The positive rate was 13.1% in lying-in women, and 4.01% in newborns. The occurrence of spontaneous abortions in anti-toxoplasma antibody positive women was 36.7%, which was higher than that in normal lying-in women. The occurrence of Fetal Distress and Asphyxia Neonatorum were 33.3% and 40% respectively, both of which were higher that those in normal newborns. PMID- 1300248 TI - [Surveillance of infectious diseases among the persons going abroad through Harbin Port]. AB - This paper reported the results of the health examination of 7447 persons going abroad and 70 persons returning home. The results showed that 349 cases carried HBsAg (with the positive rate 4.7%), and 41 cases with pulmonary tuberculosis (with the positive rate 0.6%), 4 cases with venereal disease (with the positive rate 0.05%). No AIDS and syphilis cases were detected. Suitable measures were taken for the these cases to meet the goal of surveillance. PMID- 1300249 TI - [Surveillance on ViII phage typing and antimicrobial susceptibilities of S. typhi strains in Guangdong Province]. AB - 72 S. typhi strains collected in Guangdong were tested for their Vi II phage types and their antimicrobial susceptibilities. The result of Vi II phage typing showed that 62 strains could be divided into definite types. The result of antimicrobial susceptibilities showed that, as national standard reference strains, all the 72 local strains were susceptible to choloramphenical, gentamycin, neomycin and polymycin B and were of different resistance to other 14 antimicrobial agents. The resistant profiles of strains isolated in different ages shared no significant difference. Choloramphenical remains Commonally selectable to treat Typhoid. PMID- 1300250 TI - [A carboxylated latex agglutination test for the serological diagnosis of human and animal brucellosis]. AB - A carboxylated latex agglutination test was developed for detecting antibodies in sera of human and animals with Brucellosis. The latex was chemico-linked with B. melitensis 16M extracted with 5% NaCl. Comparing with physico-sorbent latex antigens in detecting antibodies in sera of human and animals with Brucellosis, the chemico-linked latex is more stable, more specific and more sensitive. In addition, preparation of chemico-linked latex and some factors affecting the result of the test were also described in the paper. PMID- 1300251 TI - [A case-control study on the relationship between neonatal hyperbilirubaemia and usage of oxytocin during labour]. AB - Analytical method for multiple exposure level data of matching (1:1) case-control study was employed in the study on the relationship between neonatal hyperbilirubinemia and usage of oxytocin (during) in labour. The result showed that there was significant association between them (chi 2 = 15.538, df = 3, P = 0.0014). The odds ratios for various exposure level were 1-5.9 (u): OR = 1.085; 6 8.9 (u): OR = 5.5; 9 + (u): OR = 3.687 and the log linear trend among them was significant (chi 2 = 11.991, df = 1, P = 0.0005). PMID- 1300252 TI - [Study on the immunization effect of measles vaccine by capture-EIA]. AB - Capture-EIA was applied to detect specific IgM antibody (SIgM) to measles virus in paired sera from 72 children before and after primary vaccination and HI antibody was also tested simultaneously. The SIgM and HI antibodies were not detected in 72 prevaccinated and 7 post-inoculated sera by both the capture-EIA and HI test. Among the 65 sera-conversion samples by HI test in the 15 days after immunization, comparing with the results obtained by the capture-EIA, the comformability were 83-100%. The results showed that there was a certain relationship between the level of SIgM produced and the vaccine dose inoculated. So, the results indicated that for investigation of the effect of immunization with measles vaccine. Capture-EIA is as good as HI test. PMID- 1300254 TI - Disposal of sharps by mail. PMID- 1300253 TI - [Study on the medium (BALM) for isolation of Legionella pneumophila]. AB - L. pneumophila was apparently using blue algae (cyanobacteria) extracellular products as carbon and energy sources for its proliferation. Based on this observation, a medium (BALM) in which all chemicals and reagents were made in China for isolation of L. pneumophila was developed. The recoveries of L. pneumophila serogroups 1 and 6 standard strains from contaminated air-conditional water and infected guinea pig spleens were evaluated by using two culture media: BALM and BCYE (buffered charcoal yeast extract agar). Recoveries of standard strains of L. pneumophila serogroup 1 were similar on both media, while those of L. pneumophila serogroup 6 were more efficient on BALM than on BCYE. In the process of isolation of L. pneumophila NANJ-1 strain, which was obtained from the material of tracheal lavage of a pneumonic patient in one of hospitals in Nanjing City, the recovery of this strain was also more efficient on BALM than on BCYE and other common used media. The results suggested that the use of BALM medium in place of BCYE may improve the recover of L. pneumophila from clinical and environmental specimens. PMID- 1300255 TI - [A case of brain dead patient with a spinal pathology of preserved marginal white matter and pencil-shaped softening--a theory for pathogenesis of pencil-shaped softening]. AB - We reported a case of brain death which had been caused by massive cerebral hemorrhage. The spinal pathology showed preserved marginal parts of spinal white matter in the segments of C7 to T5 and S1 to S3, and the other parts showed necrosis. We found pencil-shaped softening (PS)-like lesion in the segment C8 to T2, but the lesion was more preserved than the surrounding tissue. The intraspinal structure of C5 was distorted by the necrotic cerebellar tissue in the subarachnoid space of the segment and the posterior column area was decreased. The posterior column in C5 and PS showed the same severe pathology. Because the pia mater of the spinal cord is not so easily torn, and has some elasticity, swollen spinal necrotic tissue has no place to move but in a longitudinal direction; that circumstance may cause the PS. In this case the subarachnoid cerebellar tissue restricted the expansion of the spinal cord in C5, which might have helped cause PS. So we suggest that the subarachnoidal cerebellar tissue and changes of antero-posterior diameter in the spinal column, when the spine is flexed or extended, may contribute to the pathogenesis of PS. In this case the pathology of the PS was reversed as compared to the usual PS, because the PS was relatively preserved while the surrounding tissue was necrotic. There have been only a few reports which show preserved marginal white matter of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300256 TI - [A case of parkinsonism due to pontine and extrapontine myelinolysis]. AB - A 43-year-old man who presented parkinsonism due to pontine and extrapontine myelinolysis was reported. Late in February, 1990, the patient presented suffered from a flu-like illness and was seen at a community hospital. Physical finding showed the pigmentation on the whole body and hypotension, and laboratory examination revealed severe electrolyte imbalance (serum sodium 100 mEq/l, serum potassium 6.9 mEq/l, serum chloride 68 mEq/l) and hypoglycemia (postprandial serum glucose 78 mg/dl). Given these results, adrenal failure was strongly suspected. Prompt correction of electrocyte imbalance was performed by the infusion of sodium chloride, and four days later the serum sodium level reached 131 mEq/l. On the other hand, the patient was noticed lethargic and showed parkinsonism i.e., rest tremor, cog-wheel rigidity, and hypokinesia. Fourteen days after the onset of neurological abnormalities, the patient was referred to our hospital for further evaluation of parkinsonism. Additionally, neurological examination revealed dysphagia, mutism and positive pyramidal tract sign. On admission brain computed tomography was unremarkable, but on the 14th hospital day it showed low density area in the pons. Brain magnetic resonance imaging also showed a striking increase in T2-weighted signal from the pons, the midbrain, and the bilateral thalamus. Based on these findings, a diagnosis of parkinsonism due to pontine and extrapontine myelinolysis was made, and levodopa therapy was started. After the initiation of levodopa therapy, improvement of tremor, rigidity, and hypokinesia ensued with marked functional benefit, and the patient was discharged on the 49th hospital day. Levodopa was stopped three weeks after discharge but, all neurological abnormalities were not recurrent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300257 TI - [A case of Cheyne-Stokes respiration with cyclic mutism during apneic period]. AB - A 77-year-old man showed Cheyne-Stokes respiration (CSR) without a consciousness disturbance. In each apneic period of CSR, he became mute. In the apneic and mute state, he could open his mouth or protrude his tongue, but he could not breath or speak. In this patient, it was evident that not only phonation but also speech was under the control of respiration. Neuroimaging technique revealed an infarction in the right anterior cingulate gyrus and supplementary motor area as well as the entire perfusion area of the right middle cerebral artery. Marked atrophy of bilateral cerebral hemispheres was also observed. In this case, destruction of the right cingulate gyrus was thought to manifest occult functional fluctuation of the left cingulate gyrus influenced by the respiratory control mechanisms. This case suggested that the limbic system integrates the speech mechanism and the respiratory mechanism. PMID- 1300258 TI - [Parkinson's disease with syncope as a chief complaint induced by prominent postprandial hypotension]. AB - A 77-year-old man developed syncope after meals at the age of 75. He had been treated with anti-Parkinson's drugs such as levodopa for 18 years as a patient with idiopathic Parkinson's disease (PD). The medications had been very effective to his parkinsonism. Ambulatory blood pressure was recorded every 20 minutes throughout one day by indirect measurement using a Colin medical instrument monitor (ABPM-630). The subsequent data disclosed that postprandial hypotension (PPH) was associated with the frequent after-meal syncope. It was also found that oral ingestion of a solution containing 50 grams of glucose caused a marked and prolonged hypotension during the resting supine position. Plasma norepinephrine failed to show any increment. Plasma vasopressin slightly increased while pulse rate, plasma renin activity, osmolality, and hematocrit did not change despite the production of severe hypotension of a relative acute onset. Signs of glucose intolerance and hyperinsulinemic response were observed. Indications of systemic autonomic nervous dysfunctions were revealed in various autonomic nervous function tests. Physical treatment combined with medication such as droxidopa, midodrine and especially caffeine and fludrocortisone proved to be effective on PPH. The authors confirmed the existence of PD with symptomatic PPH. In addition, we considered this present case as an example of "progressive autonomic failure with PD" (Bannister, 1988). PMID- 1300259 TI - [A case of thalamo-subthalamic hemorrhage presenting monoballism in the contralateral lower extremity]. AB - We report a 62-year-old man with ballism confined to the right leg, so-called monoballism. He was admitted to our hospital complaining of gait disturbance due to violent involuntary movements in the right lower extremity which had developed seven days before. He had a ten-years' history of hypertension and at age 57 had been diagnosed as having asymptomatic multiple cerebral infarcts. Until admission, he was taking antiplatelet drugs for the purpose of preventing thrombotic stroke. On neurological examination, he showed mild impairment of higher brain function, Horner's sign in the left eye, and typical ballism in the right lower extremity. Involuntary movements were never observed in the face and the other extremities. Surface electromyography also showed reciprocal burst discharges at about 1 Hz related to the ballistic movements in the right lower extremity. CT scan revealed a high density lesion surrounded by a low density in the left subthalamic area. MRI examination demonstrated a dumbbell shaped hemorrhage extending from the left subthalamic nucleus to the dorsomedial nucleus of the ipsilateral thalamus. Adding to the hemorrhage, many ischemic lesions were observed in the bilateral basal ganglia and thalamus including the left pallidum. The causal end of the hemorrhage apparently located in the anterior dorsomedial portion of the subthalamic nucleus. There were few reports concerning monoballism, especially monoballism limited to the lower extremity. Recent researches indicate that a subthalamic lesion reduces the excitatory control from the subthalamus to the internal segment of the globus pallidus, which leads to a disinhibition of the thalamus and gives rise to ballism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300260 TI - [A case of foreign-body granuloma treated with steroid hormone]. AB - A 68-year-old woman was admitted to Nagasaki University Hospital complaining of gait disturbance. She had suffered from hemifacial spasm since the age of 56 and had undergone neurovascular decompression for the spasm in another hospital five years before admission. At surgery, the vertebral and posterior inferior cerebellar arteries had been separated from the facial nerve with cotton string and attached to the clivus with alpha-cyanoacrylate monomer. Although the hemifacial spasm had improved postoperatively, the patient had suffered from gait disturbance and headache for two months after surgery, and hearing disturbance and hemifacial palsy on the same side as the hemifacial spasm for seven months after surgery. At the time of the present admission, contrast-enhanced CT scan revealed a mass at the left cerebello-pontine angle. In the T1-weighted inversion recovery sequence of MRI, the mass showed a slightly lower intensity than that of surrounding tissues. In the T2-weighted spin echo sequence of MRI, it showed a heterogenously low intensity with some high intensity spots. We diagnosed this mass as a foreign-body granuloma and treated it with dexamethasone injected intramuscularly. Edema decreased around the granuloma, and her gait disturbance improved markedly. But the hearing disturbance and hemifacial palsy did not improve at all, indicating that these two symptoms might not be caused only by brain edema but also by direct damage due to granuloma or inflammation. We thought that the steroid hormone elicited good results in the treatment of inoperable foreign-body granuloma. PMID- 1300261 TI - [A case of early onset cerebellar ataxia with hearing loss, mental disturbance and primary hypogonadism]. AB - A 14-year-old girl, whose birth and developmental history were normal till the age of 7, was admitted to our hospital because of slowly progressive difficulties in walking, speaking and hearing. She also complained of absence of menstruation. She showed poor school records since the age of 7. On neurological examination, she showed limb and truncal ataxia. There was no nystagmus but slurred speech was found. Muscular power was good and her sensory system was normal. Tendon reflexes were equally present, and plantar reflexes were flexor. Bilateral moderate nerve deafness was also present. Mental deficiency was diagnosed on an intelligence test. Brain CT and MRI showed cerebellar atrophy. Gynecological examination revealed scanty pubic hair and small uterus. Karyotype was 46XX. Endocrinological studies demonstrated high level of FSH, low level of E2, and the normal response to pituitary stimulation with LHRH, indicating the existence of primary hypogonadism. Although the etiology of this multisystem disorder is unknown, it is possible that both nervous and endocrine disorders were genetically determined. PMID- 1300262 TI - [An adult case of transverse myelitis with erythema infectiosum]. AB - We reported an adult case of transverse myelitis with erythema infectiosum. A 33 year-old female was admitted to Kyoto University Hospital because of a weakness in the lower extremities and "cloth-wearing" sensation of the trunk and legs. One month before admission, she became febrile and developed a symmetrical erythema on the extremities. At the same time she noticed a slight weakness of the legs and numbness in her fingers and toes, which disappeared next few days. A week later, she again developed a fever, severe weakness of the legs and "cloth wearing" sensation on the trunk, and erythema appeared on the cheek. Physical examination on admission revealed a weakness and hyperreflexia in the extremities, in particular, knee and ankle jerk, and hypesthesia of the trunk and legs below the level of Th6. Cerebrospinal fluid (CSF) examination revealed 181/mm3 cells (mononuclear cell dominant) and 30 mg/dl protein. Magnetic resonance imaging, CT and electrophysiological studies indicated no abnormalities. IgM antibody against human parvovirus (B19) was detected in the serum and CSF. She was diagnosed as transverse myelitis with parvovirus infection and was medicated with prednisolone 40-60 mg/day, and improved gradually with the residua of a mild weakness of the legs and hypesthesia on the trunk between the level of Th6 and Th10. PMID- 1300263 TI - [A mother and her son with autosomal dominant bulbar spinal muscular atrophy]. AB - We reported a 49-year-old mother and her 28-year-old son with autosomal dominantly inherited bulbar spinal muscular atrophy (AD-BSMA). They showed progressive bulbar paresis, muscle wasting and weakness dominant in the proximal groups of limb muscles, and finger tremor. Onset of illness was in adult life. In laboratory examinations, elevated creatine kinase in serum and neurogenic changes either in EMG or muscle biopsy were noted. The son had neither gynecomastia nor abnormal sexual hormone levels which were observed in the sex-linked recessive bulbar spinal muscular atrophy (SR-BSMA). Elongation due to the CAG repeats at the androgen receptor gene of the X chromosome in SR-BSMA was not detected. In conclusion, it is clear that AD-BSMA is different from SR-BSMA on the basis of clinical and genetical aspects. PMID- 1300264 TI - [Multiple mononeuropathy during recombinant interferon-alpha 2a therapy for chronic hepatitis C]. AB - Reported is a case of multiple mononeuropathy which appeared during the administration of recombinant interferon-alpha 2a (rIFN-alpha 2a) for treatment of chronic hepatitis C. A 38-year-old man received an intramuscular injection of rIFN-alpha 2a, 6 x 10(6) IU, every one or two days for a nine week period. Seven weeks after the initiation of rIFN-alpha 2a therapy he developed numbness of the tongue and extremities and weakness of the upper extremities. Neurological examination revealed an asymmetrical disturbance of touch and pain sensation in the tongue, trunk, left shoulder and extremities accompanied by painful dysesthesia. Moderate weakness and muscular atrophy were noted in the right hand and left shoulder. Electrophysiological studies showed the amplitude of the compound muscle action potentials and sensory nerve action potentials were significantly decreased, when the right median and ulnar nerves were stimulated. Additionally, the conduction velocities were normal and needle electromyography showed fibrillation potentials suggesting an axonal form of multiple mononeuropathy. Biopsies of the muscle and nerve failed to show pathological changes, however. The clinical and electrophysiological abnormalities reduced gradually with methyl-prednisolone pulse therapy and administration of prednisolone and mizoribine. Therefore, in this case, administration of rIFN alpha 2a may have induced multiple mononeuropathy of the axonal form. PMID- 1300265 TI - [Isolated angiitis of the central nervous system with high immune complex titer, first presenting as intracranial hemorrhage during cesarean section]. AB - A case of isolated angiitis of the central nervous system (IACNS) which first presented as intracranial hemorrhage during cesarean section was reported. The patient was a 27-year-old female who showed severe headache during cesarean section. CT scan disclosed hematoma in the right parieto-occipital area. Carotid and vertebral angiograms demonstrated striking areas of stenosis and irregularity of all intracranial arteries. There was no abnormality in the branches of the external carotid arteries. Systemic angiograms showed no evidence of systemic vasculitis. Biopsy of the temporal artery showed no abnormal findings. Titer of immune complex was elevated. Angiitis showed no improvement with corticosteroid alone, but improved markedly with corticosteroid plus cyclophosphamide. Elevated titer of immune complex became normal. Treatment with a combination of corticosteroid and cyclophosphamide is recommended in IACN. PMID- 1300266 TI - [Multivariate analysis of the clinical signs in late cortical cerebellar atrophy (LCCA) in Japan--compared with olivo-ponto-cerebellar atrophy (OPCA) and hereditary cortical cerebellar atrophy (HCCA)]. AB - We investigated the clinical features of 179 patients with late cortical cerebellar atrophy (LCCA) comparing with 382 patients with olivo-ponto-cerebellar atrophy (OPCA) and 91 patients with hereditary cortical cerebellar atrophy (HCCA) using multivariate analysis. They had no significant difference in durations from onset. Disorders of finger-nose test were of more severity and disorders of heel knee test were less involved in LCCA than in HCCA. Eye movements tended to be normal in LCCA. LCCA showed more depressive and euphoric character than OPCA and HCCA. Analysis of LCCA and OPCA demonstrated that LCCA revealed hypotonia in muscles, normal or weak reactions of muscle stretch reflexes. There existed 21.4 percent of cases which could not be discriminated by multivariate analysis using clinical signs in LCCA and OPCA. Multivariate analysis of LCCA and HCCA, which are very similar in clinical signs, showed 66.3 percent of discriminatory rate. Thus, we could diagnose them to a certain extent only by clinical signs. PMID- 1300267 TI - [Mechanism to induce scoliosis in Duchenne muscular dystrophy--a study of paraspinal muscle by X-ray computed tomography]. AB - We studied mechanism to induce scoliosis in Duchenne muscular dystrophy (DMD) by use of X-ray computed tomography (CT) of paraspinal muscles. CT examination of paraspinal muscles was performed on 15 DMD patients at the following six levels; 1. Th3 vertebrae (upper thoracic spine level) 2. Th6 vertebrate (middle thoracic spine level) 3. Th10 vertebrae (lower thoracic spine level) 4. L1 vertebrae (upper lumbar spine level) 5. L3 vertebrae (middle lumbar spine level) 6. L5 vertebrae (lower lumbar spine level). We evaluated the degeneration of paraspinal muscle by a decrease in radio-density of the muscle which indicates infiltration of fatty tissue. The degeneration of the lateral portion of paraspinal muscle was more marked than that of the medial portion. The muscle was most severely affected at the middle lumbar spine level, showing a tendency to increase degeneration at the lower level of the spine. In cases showing laterality of the degeneration of paraspinal muscle, the less affected muscle on CT was located at the convex site of scoliosis. We speculate that the scoliosis occurs when DMD patients have asymmetrical paraspinal muscle degeneration, leading them to take compensatory posture. PMID- 1300268 TI - [A new method of gait analysis in Duchenne muscular dystrophy]. AB - We assessed gait in Duchenne muscular dystrophy (DMD) mainly by determining alteration of foot pressure using a new gait analyzing procedure. DMD patients showed a characteristic foot pressure pattern according to their degree of dysfunction. In stage I disease, the observed pattern was the same as that of normal controls. In stage II, the period during which the center of foot pressure was seen in the front part of the foot was prolonged. This change became more marked in stage III. In stage IV, the center of foot pressure began at the head of the ossis metatarsalis primi and moved back and toward the lateral side. Thereafter, the center of foot pressure again moved forward along the outside of the foot. These changes were considered to be the result of talipes equinus and waddling gait, which are commonly demonstrated in patients with DMD. PMID- 1300269 TI - [Central nervous system lesion in myotonic dystrophy--demonstrated by X-ray computed tomography and magnetic resonance imaging]. AB - We made an attempt to detect organic brain lesions in eight patients with myotonic dystrophy (MyD) using X-ray computed tomography (CT) and magnetic resonance imaging (MRI). The patients comprised seven men and one woman with ages ranging from 41 to 58 years (average 47 +/- 5.3 years). Seven patients had intellectual impairment assessed using an intelligence quotient test (WAIS-R < 70). CT scans were obtained in the axial plane with a slice thickness of 10 mm, and MRI scans were performed on a 1.5 tesla system in the axial and coronal sections with a slice thickness of 8 mm. CT scans displayed both marked sulcal and prominent ventricular enlargement in 6 of the 8 patients, indicating the presence of brain atrophy, and 3 cases had a few paraventricular low density area in the cerebral hemispheres. In contrast to CT, MRI study revealed more widespread brain parenchymatous lesions in all the 8 cases, showing the multiple foci of high signal intensity with varying size in the white matter on T2 weighted images and proton density-weighted images. No visible changes were detected on CT or MRI in the brain stem and cerebellum. The present study demonstrated that there exist organic cerebral lesions, predominantly located in the white matter in patients with MyD, regardless of focal neurological symptoms. The parenchymatous lesions in the brain can be detected with MRI, and lesser extent with CT, and are considered to be intimately correlated with intellectual deterioration commonly seen in patients with MyD. PMID- 1300270 TI - [Influence of protein-restricted diet on motor response fluctuations in Parkinson's disease]. AB - The clinical management of Parkinson's disease has been revolutionized by the introduction of levodopa therapy. It has significantly reduced disability and has extended life expectancies of patients with Parkinson's disease. However, motor response fluctuations frequently appear in patients after long-term treatment with levodopa. In this study, we investigated the effect of protein-restricted diet on fluctuations in eight patients with Parkinson's disease who had been receiving long-term levodopa treatment (mean 12.5 years). Two weeks of protein restricted daytime diet (7.5 g total at breakfast and lunch) was followed by 12.5 g total at breakfast and lunch. At night, high-protein diet (40-50 g at dinner) was offered to the patients in order to maintain total daily protein intake at Japanese standard level. The medication schedule of levodopa and other antiparkinsonian drugs was not changed within 2 weeks after the study was began. Fluctuations were reduced in 7 of the 8 patients. But in only one patient (case 6), dyskinesia and general condition got worse and stopped this therapy. Body weight, serum protein and albumin levels did not change significantly for at least three month after the study was begun in every 6 patients who were examined. Homovanillic acid level of cerebrospinal fluid reduced in every 4 patients who were examined. We concluded that protein-restricted diet during the daytime offers a fascinating technique for the control of motor response fluctuations in patients with Parkinson's disease undergoing long-term levodopa treatment. But this therapy must be indicated carefully. Mechanism of this therapy may has something to do with improvement of dopamine metabolism in the brain. PMID- 1300271 TI - [The pattern of neurological deterioration and the mechanism of neurological deficit in syringomyelia]. AB - Sixty-five cases of syringomyelia were evaluated. The cases were classified into two groups: group 1 (56 cases) was patients who presented with hind-brain related syringomyelia and group 2 (9 cases) was patients who presented with primary spinal syringomyelia. Group 1 was further divided into two subgroups, group 1a and group 1b: group 1a (46 cases) consisted of patients with hind-brain related syringomyelia without basal arachnoiditis and group 1b (10 cases) consisted of patients with hind-brain related syringomyelia with basal arachnoiditis. The most common initial symptom of group 1a patients was abnormal motor function of an upper limb (14 cases), followed by pain in an upper limb (12 cases), and dissociated sensory loss (10 cases). In group 1b, motor symptoms of an upper limb were also the most common initial symptom, again followed by pain in an upper limb. Paraplegia was the most common initial symptom in group 2. About 80% of patients in groups 1a and 1b had both sensory and motor deficits at the time of examination and the majority of group 1b patients also had brain stem signs and/or pain. Brain stem signs were not commonly seen in group 1a patients, however. The neurologic deficits of group 1b patients were generally more severe than those of group 1a patients. Most group 2 patients also had sensory and motor deficits of both lower limbs. The progression of neurological deficits in groups 1a and 1b was classified into four stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300272 TI - [Therapeutic effect of lymphocytapheresis on patients with HTLV-I-associated myelopathy (HAM)]. AB - Lymphocytapheresis (LCP) was performed in 7 patients (1 male and 6 females) with HAM to delete lymphocytes from their peripheral blood, resulting in an improvement of motor disability in 6 of 7 patients with HAM. The therapeutic effect appeared within one day after first LCP, and reached maximum in 2 or 3 sessions of LCP. The side effects were only dysesthesia in 5 patients during LCP and mild leukopenia in a patient after LCP. Both of them were mild and transient. The effect of LCP continued for two to five months in 6 patients, the remaining one deteriorated in a month. In the study of T cell subsets of peripheral blood lymphocytes by flowcytometry, the CD4/8 ratio and the cell counts of CD4+ DR+, CD8+ DR+ and IL-2R positive cells were gradually decreased by LCP. These results suggest that LCP is one of the effective therapies for HAM and peripheral blood lymphocytes implicate in the pathogenesis of HAM. PMID- 1300273 TI - [Chorea associated with antiphospholipid antibodies]. AB - We report a 21-year-old woman in whom chorea was associated with antiphospholipid antibodies. In August 1986, she developed involuntary movement which started in the right hand but subsided spontaneously. In September 1988, she again developed right-sided involuntary movements which started in the right hand but rapidly progressed to involve the whole of the right side. In September 1990, she was admitted to our hospital for investigation of choreiform movements, because her involuntary movements had progressed to involve all four extremities. She had no family or past history of chorea, psychiatric, rheumatological or vascular disease. On admission, she had difficulty in speaking and swallowing due to choreiform movements of her mouth and tongue. Her gait was unsteady. On walking she had wild gyrations of the arms. Choreiform movements of all four extremities, neck, face, mouth and tongue were present at rest, more marked on the right side. There was no other neurological deficits. She had none of the classical features of SLE. She had none of the complications commonly associated with antiphospholipid antibody syndrome (APS) (i.e., recurrent spontaneous abortion, thrombosis and thrombocytopenia). Laboratory tests revealed that antinuclear antibody was present. Cardiolipin antibody (VDRL) was positive but specific tests for syphilis were negative. Anticardiolipin antibodies were present. All coagulation studies have failed to reveal lupus anticoagulant. Brain CT, MRI, 123IMP-SPECT and cerebral angiography were normal. Associated with her chorea, she had the serological but not the clinical features of APS. We suggest that antiphospholipid antibodies should be looked for in all unexplained cases of chorea, even when the associated clinical signs of APS are absent. PMID- 1300275 TI - [Information on diagnosis and treatment in ovarian cancer]. PMID- 1300274 TI - [A case of early syphilis presenting general paresis-like symptoms and bilateral tonic pupils]. AB - A 40-year-old man was admitted after 8 months of speech disturbance and locomotive ataxia. He had no seizures, lightning pains, paresthesia, visual loss, bladder disturbance or rectal incontinence. He had never been neurologically or psychiatrically ill and had no history of syphilis. When the patient was admitted, his general physical examination including blood pressure and dermatologic examination was normal. His consciousness was alert. He was found to have a deterioration of mental status such as inability to concentrate, failing memory, amnesia and circumstantiality. His pupils were anisocoric and Achilles jerks were absent. No rigidity of the neck muscles, paralysis and sensory disturbance were recognized. Romberg's sign was absent. The right pupil was 7.0 mm and the left was 6.0 mm in room illumination. The pupils were nonreactive to bright light and both did not constricted to near stimuli. 0.125% pilocarpine eyedrops produced bilateral pupillary constriction. The results indicated bilateral tonic pupils. Laboratory data revealed white cell count of 12,600/mm3 and normal erythrocyte sedimentation rate of 8 mm/hr. Cerebrospinal fluid (CSF) examination revealed the following: opening pressure, 140 mm of water; cell counts, 76/mm2 (mononuclear cells); total protein, 116 mg/dl; glucose, 57 mg/dl. A serum venereal disease research laboratories (VDRL) test was positive in a 1:32 titer confirmed by positive treponema pallidum hemagglutination (TPHA) test in a 1:40,960 titer and positive fluorescent treponemal antibody-absorption (FTA-ABS) test. Serum TPHA-IgM was positive in a 1:320 titer but TPHA-IgG was negative. CSF examination revealed positive TPHA test (titer of 1:2,560) and positive FTA-ABS test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300276 TI - [Comprehensive analysis of histological types in 14006 cases of ovarian tumors]. AB - Fourteen thousand and six cases of ovarian tumors were reported by 15 hospitals in Zhejiang and other 5 provinces. Of all the tumors, there were 3,363 cases (24.0%) of malignancy. According to the criteria based on WHO's classification, malignant tumors of the ovary comprised of 1,999 cases (59.4%) of epithelial cancer, 646 cases (19.2%) of germ cell tumors, 273 cases (8.1%) of metastatic tumors, 236 cases (7.0%) of sex cord stromal tumors and 209 cases (6.2%) of other tumors. Mucinous cystadenocarcinoma was found to be the most frequent in borderline epithelial tumors, while serious cystadenocarcinoma to be the most one in malignant epithelial tumors. Dysgerminoma, endodermal sinus tumors and immature teratomas appeared to be similarly frequent in malignant germ cell tumors. The tumors metastasizing from gastroenteric carcinoma was the commonest in metastatic tumors. Compared with reports abroad, the different types of malignant ovarian tumors in China have the different distributive patterns. It is very important to pay attention to prevent and early diagnosis of malignant ovarian cancer. PMID- 1300277 TI - [Lymph node metastasis in stage I ovarian cancer]. AB - One hundred and sixteen cases of stage I Ovarian cancer from nine hospitals in all the China during Sept. 1982-April 1991 were investigated for their lymph node metastasis. There were 70 epithelial tumors, 36 malignant germ cell tumors, 8 from gonadal stroma and 2 undifferentiated. In 89 patients the ovarian tumor was confined to one ovary (stage Ia); in 6 cases both ovaries were involved (stage Ib); 21 cases was documented stage Ic. Systemic lymphadenectomy covering all pelvic groups of node together with aortic lymph node accomplished in 82 cases. In the remaining 34 cases only pelvic lymph node dissection was performed. There was 10.3 percent incidence of lymphatic metastasis in this series. The most common lesion was serous cystadenocarcinoma. All patients were follow-up for at least half year. The mortality rate in patients without lymph node metastasis was 2.8%, but 8.3% for those with lymph node metastasis. The clinical significance of retroperitoneal lymphadenectomy in early ovarian cancer was discussed. PMID- 1300278 TI - [Surgical treatment of cervical cancer]. AB - The clinical data and long-term following up results of 1,320 cases of cervical cancer from Jan. 1 st, 1953 to Dec. 31 th 1988 were presented. The routine operative extent for invasive cervical cancer in this hospital has been radical hysterectomy and pelvic lymphadenectomy. The cardinal ligament, para-vaginal tissue and vaginal wall removed varied according to the different clinical stage and extent of the lesion. The operative complications were: trauma 0.8%, the postoperative complication of ureteral fistula 0.2%, and there were no operative death. Long-term following up rate were 99.8%. In this series. The cumulative survival rate calculated by computerized life table method were following: 5 year survival rate sq. cell ca. stage Ia 100%, stage > or = I b 97.6%; adenoma. 90.8%. 185 cases died, among which 60 cases died of recurrent cervical cancer, 85 cases died of other benign diseases, 40 cases died of primary cancers of other organs other than cervix of uteri. It denotes that once a patient suffers from one kind of cancer, she will have possibility of suffering from another kind of cancer. PMID- 1300279 TI - [Influence of passive smoking on the fetus during pregnancy]. AB - The study on the hazard of passive smoking to the fetus during pregnancy was carried out in 188 cases. The rate of SGA, premature labor and neonatal asphyxia in this group were higher than that of 65 cases without passive smoking. The data was analysed by logistic multifactor regression analysis. The result showed that, for those patients with hypertension and husband smoking, the risk of SGA, and neonatal asphyxia were 1.6, 2.8 and 3.2 times higher than those without hypertension and husband smoking. In the group of passive smoking, their blood CoHb and umbilical venous CoHb levels were obviously higher than those of the normal control. The possible cause of hazard of passive smoking to the fetus was also analysed and discussed. PMID- 1300280 TI - [Stereological study of the placentae in intrauterine growth retardation with different ponderal index]. AB - 10 placentae each from the cases of IUGR with normal ponderal index (NPI) and low ponderal index (LPI) and 10 from normal pregnancy as control were analysed quantitatively with stereological principles. This study showed the placental weight, volume, surface area of villi and villous fetal capillary in IUGR were significantly reduced than that in control group. The percentage ratio of the fetal capillary volume was increased significantly in IUGR group but the ratio of vasculo-syncytial membrane/villous fetal capillary decreased. It suggested that compensation to anoxemia in placenta of IUGR was incomplete. The data also found that all the parameters in NPI group were decreased significantly than that in LPI group, which implied NPI group had a more severe growth deficiency of the placental functional structure. When placental growth deficiency occurs in the first or second trimester, both the fetal length and weight will be severely affected. PMID- 1300281 TI - [Eclampsia complicated with cerebrovascular disease]. AB - Ten eclamptic patients complicated by acute cerebrovascular disease were admitted during the past eight years from Feb. 1982 to Feb. 1990. There were six cases of superior sagittal sinus thrombosis, two cases of cerebral hemorrhage, one cases of subarachnoid hemorrhage and the other one of cerebral infarction. Among them, eight patients were cured. Our analysis demonstrates that it is advisable to terminate pregnancy by cesarean section as soon as possible. A comprehensive management proposed by good cooperation between neurologist, neurosurgeon and obstetrician is the key to get a good way to cure these patients. PMID- 1300282 TI - [Doppler velocimetry measurement in pregnancy complicated with diabetes mellitus]. AB - To evaluate the effects of diabetes mellitus (DM) on fetoplacental circulation, Doppler velocimetry was carried out in diabetic pregnant women (n = 21) and normal pregnant controls (n = 20) every 2 weeks from the 20th week of gestation till term. Blood flow wave form of umbilical artery (Um) and uterine artery (Ut) were measured and the systolic/diastolic ratio (S/D) of Um and Ut calculated. The results showed that the Um and Ut S/D ratio of diabetic mothers with AGA babies (n = 15) and normal controls were not different. The S/D ratio of diabetic women with LGA newborns (n = 6) elevated after the 30th week of gestation, and the time of elevation was in accordance with the accelerating growth stage of LGA fetus. It is suggested that the elevation of S/D ratio may be related to the increasing requirement of blood supply for LGA babies in DM mother. PMID- 1300283 TI - [Intra-arterial infusion chemotherapy of female genital neoplasms]. PMID- 1300285 TI - Compendium of food additive specifications. Addendum 1. Joint FAO/WHO Expert Committee on Food Additives. PMID- 1300284 TI - If you're fiftysomething, you can't afford to neglect retirement planning. PMID- 1300286 TI - Meat and meat products in human nutrition in developing countries. PMID- 1300287 TI - Understanding Capitation. PMID- 1300288 TI - Salaries take increasing share of overhead costs. PMID- 1300289 TI - Finding the path to success. PMID- 1300290 TI - Listen for the meaning. PMID- 1300291 TI - No more space or privacy problems. PMID- 1300292 TI - Dentists face new tax rules. PMID- 1300293 TI - Flexible ceramic bonding. PMID- 1300294 TI - Construction, placement and utilization of temporary veneers. PMID- 1300295 TI - Practical ideas for difficult extractions. PMID- 1300297 TI - Atlas of Cancer Mortality in the European Economic Community. PMID- 1300296 TI - Infection control in a changing world. PMID- 1300298 TI - Expulsive choroidal haemorrhage. AB - Expulsive choroidal haemorrhage is a dramatic and serious complication of cataract surgery that occurred in five patients out of ten thousand consecutive cataract surgeries performed by the author during the year 1989 and 1990. Report about this dreaded complication after cataract surgery are scanty and as far as I can remember I have not seen any report in Indian ophthalmic literature recently. Since cataract surgery forms the major part of intra ocular surgeries performed in our country, I thought it would be appropriate to report about this rare complication which may occur to all of us. Out of five cases 3 were males and 2 were females in the age group ranging between 45-72 years. Two eyes regained vision up to 6/12 after intra operative expulsive haemorrhage. All the eyes were salvaged by doing anterior sclerotomy. Diabetes, hypertension, glaucoma and myopia are the commonest predisposing factors. PMID- 1300299 TI - Subconjunctival total excision in the treatment of chronic chalazia. AB - A technique of subconjunctival total excision was used to treat 34 chronic chalazia. Another 34 were treated by incision and curettage and a further 32 by intralesional injection of long acting steroid. Subconjunctival total excision showed a higher success rate (94.12%) compared to the incision and curettage group (76.47%) and the injection group (75%). As the difference was statistically significant and due to other advantages we recommend subconjunctival total excision as a primary approach in the treatment of chronic chalazia. PMID- 1300300 TI - Compendium of dietary sources of vitamin A in the Thar desert. AB - The undisputed long term solution to prevent nutritional blindness lies in changing the dietary habits of a given population through nutritional education, nutritional supplementation, and nutritional rehabilitation. Before such strategies can be successfully implemented, it becomes necessary to study the existing dietary pattern of the population and to identify locally grown foods rich in vitamin A. Seventy eight rural women were interviewed to determine the common dietary items in western Rajasthan. These items were then matched with their B-carotene contents, only to discover that, 100 grams of any of them would not provide the RDA for a 1-3 year old child, with the exception of Suva (Peucedanum graveolens) and Bathua (Chenopodium album) leaves. The B-Carotene contents of several food items is unknown at present and there is an urgent need to evaluate them. PMID- 1300301 TI - Preoperative topical flurbiprofen-Na+ in extracapsular lens extraction role in maintaining intraoperative pupillary dilatation. AB - Induction of intraoperative pupillary constriction, is predominantly a prostaglandin mediated process. The most potent antiprostaglandin NSAID, Flurbiprofen was used topically to study its efficacy against the above. In a prospective double blind clinical study, 50 brown eyes undergoing planned E.C.C.E., the pupils were dilated with 10% phenylephrine and 2% homatropine 1%/tropicamide. 25 eyes received 0.03% Flurbiprofen-Na+ eye drops 1/2 hourly starting two hours before surgery. The maintained intraoperative mydriasis in the two groups before anterior chamber entry (stage I) vs at the end of complete cortex wash (stage III) was: in control group (stage I) 8.46 +/- 0.48 mm vs (stage III) 3.56 +/- 0.43 mm (highly SS); in flurbiprofen group (stage I) 8.60 +/ 0.48 mm vs (stage III) 8.01 +/- 0.63 mm (NSS). The pupillary area available for surgical manipulation in the control group was significantly decreased from 56.18 mm2 in state I to 9.94 mm2 in stage III, while in flurbiprofen group it changed insignificantly from 58.05 mm2 in stage I to 50.24 mm2 in stage III. Postoperatively after cataract was observed in 44% eyes of control group as compared to only 8% of eyes of flurbiprofen group. Thus a maintained intraoperative mydriasis in flurbiprofen group led to better E.C.L.E. which is a mandatory prerequisite to preferred and better present day posterior chamber IOL implantation. PMID- 1300302 TI - Ipsilateral Coat's reaction in the eye of a child with en coup de sabre morphoea- a case report. AB - A female child with post-traumatic en coup de sabre type of morphoea (fronto parietal circumscribed scleroderma) involving the left side of the forehead and face, who developed a Coat's disease-like fundus picture over the following two years, is being reported. PMID- 1300303 TI - Eltroxin induced pseudotumour cerebri--a case report. PMID- 1300304 TI - Acanthamoeba keratitis--a report of two cases. AB - Two cases of unilateral corneal ulcers caused by Acanthamoeba are reported. Neither of the patients had contact lenses at any time. The diagnosis was confirmed by Giemsa stain and cultures of the corneal scrapings. PMID- 1300305 TI - Expulsive haemorrhage. PMID- 1300306 TI - Butylated hydroxyanisole produces both mutagenic and desmutagenic derivatives under gastric conditions. AB - Dietary butylated hydroxyanisole (BHA) has been known to have inconsistent functions on carcinogenesis, both prevention and initiation. We assumed that both functions of BHA were introduced by the derivatives formed after the reaction with gastric components such as nitrite in the stomach. We then identified the derivatives produced by incubating BHA with sodium nitrite at pH 2.0 or pH 5.0. Eight derivatives were detected; 2-tert.-butyl-p-quinone (BQ), 3,3'-di-tert. butyl-biphenyldiquinone-(2,5,2',5') (BBDQ), 2,6-di-tert.-butyl-8-hydroxy dibenzofuran-1,4-quinone (BHDQ), 6-nitro-BHA, 2,2'-dihydroxy-3,3'-di-tert.-butyl 5,5'-dimethoxy-biphenyl (di-BHA), an oxidized product of di-BHA, and two unstable reaction intermediates. BQ was a major final product at pH 2.0, but not at pH 5.0. 6-Nitro-BHA and the oxidized products of di-BHA were also the final products. BBDQ was formed from di-BHA and easily converted to BHDQ. Their mutagenicity and desmutagenicity were assayed using Salmonella typhimurium strains. BQ and BBDQ were the mutagens of base-substitution type, BHDQ was the potent desmutagen against a mutagenicity of Trp-P-2, and the others had neither of the two activities. Thus, BHA was found to produce both the mutagen and desmutagen under the gastric conditions. BQ has been previously reported to be easily detoxified by glutathione, and BHA itself is well known to prevent carcinogenesis. In the assessment of dietary BHA on carcinogenesis, since one of the mutagens from BHA is easily detoxified in our bodies and another is converted to a desmutagen, BHA appears to be one of the favourable chemicals for us. PMID- 1300307 TI - Altered interleukin-1 production in mice exposed to rotation stress. AB - This study examined the effects of rotation stress (78 circles per 1 min for 1 h: 10 min rotation + 5 min interval) on peritoneal macrophage release of lymphocyte activating factors (LAF) and interleukin-1 alpha (IL-1 alpha) concentration in mice (CBA x C57BL6)F1. Rotation stress induced the macrophages' release of LAF with peak reactions in 0-1 h after termination of stress, followed by elevation of plasma IL-1 alpha. Induction of LAF release was accompanied by a higher concentration of corticosterone (Cs) in the blood, most prominent at 0 and 0.5 h after termination of the stressful procedure, and recovering to normal values 1 h later. It is suggested that the stimulating effect of stress on LAF and IL-1 production possibly involves glucocorticoid hormones, as well as other stress induced neurohumoral shifts accompanying the reaction of glucocorticoids. It is also possible that the activated production of LAF and IL-1 by macrophages has a stress-limiting role in cases of mild stress. PMID- 1300308 TI - Role of endothelin-1 in carrageenin-induced inflammation. AB - Many vasal factors are produced during an experimental model of inflammation such as rat-paw oedema induced by carrageenin. We investigated whether among the other well-known mediators of inflammation, i.e. serotonin, PAF, eicosanoids and kinins, the peptide endothelin-1 is produced by this kind of inflammatory process caused by carrageenin. Our results indicated that plasma endothelin, and the tissue concentration of endothelin in the oedematous paw, is increased as compared to the control. Consequently, endothelin should also be considered as an important factor in inflammatory processes. PMID- 1300309 TI - In-vitro evaluation of drugs proposed as chondroprotective agents. AB - Three proposed chondroprotective agents (CP), namely glucosamine sulfate (GAS), chondroitin sulfate (CS) and glycosaminoglycan-peptide complex (GP-C), were tested on differentiated human articular chondrocytes cultured in clusters. Chondrocyte productions of proteoglycans (PG), type II collagen (coll. II) and prostaglandin E2 (PGE2) were established by specific radioimmunoassays applied to the culture medium (CM) and in chondrocyte clusters (CC). Collagenolytic activity was assayed in CM. DNA synthesis, studied by measuring 3H-thymidine incorporation, was unaffected by CS and GAS. GP-C, at low concentration, stimulated DNA synthesis. GP-C, at higher doses, induced a high increase in PG and coll. II productions. GAS and CS induced a stimulatory effect limited to PG production. None of the CP tested here affected the basal PGE2 production by human chondrocytes. PMID- 1300310 TI - Clinical research in osteoarthritis: design and results of short-term and long term trials with disease-modifying drugs. AB - Putative disease-modifying drugs are usually clinically used in osteoarthritis with two main aims: not only stopping or reducing the cartilage degenerative process after a long-term treatment, but also controlling the symptoms of the disease within a few days or weeks, thus avoiding or diminishing the use of symptomatic medications. Due to the difficulties of implementing the first aim, the latter aim was more often investigated, even if most often with inadequate study design and insufficient numbers of patients. We have recently carried out three double-blind, controlled, parallel groups, randomized, 4-6 week trials of glucosamine sulphate versus placebo or the NSAID ibuprofen on a total of 606 gonarthrosic out-patients. Movement limitation and pain were scored according to the Lequesne index, and the efficacy goals were strictly pre-determined. Access to other medications was not allowed. Glucosamine was significantly more effective than placebo, while no difference was detected in comparison with the NSAID (p < 0.025 and p = 0.77, respectively: Fisher's two-tailed exact test). On the other hand, glucosamine was as well tolerated as placebo, while the percentage of patients suffering adverse drug reactions was higher in the ibuprofen group (37% vs 7%: p < 0.001). Long-term trials are in progress and several aspects are to be considered in their design: they must be double-blind, placebo-controlled, randomized, continued for a period of years and (most importantly) with the careful use of imaging and biochemical techniques capable of generating objective evaluation criteria. PMID- 1300311 TI - Antireactive properties of "chondroprotective" drugs. AB - The medicinal therapy of osteoarthritis is based on the use of analgesics, NSAIDs and corticosteroids to relieve pain and inflammation. In addition, "chondroprotective" agents (CPA) are used to stop the evolution of the disease. In this review the biochemical and pharmacological activities of some of the most widely used CPAs are described. All of these show more or less marked antiinflammatory activities, which for some of them are the result of an inhibition of cyclo-oxygenase and of prostaglandin biosynthesis, in which case they should be more properly classified as mild NSAIDs. Only two of the CPAs reviewed, diacerein and D-glucosamine sulfate, elicit antiinflammatory and antireactive effects without significant inhibition of the prostaglandin biosynthesis. These agents have also remarkable chondroprotective effects, and only these two agents should be classified as true CPAs. In particular glucosamine sulfate, which naturally occurs in the human body and is almost devoid of toxicity, is suitable for long-term therapeutic use. This, with its chondrometabolic, antireactive and antiarthritic properties, represents the pharmacological rationale for the use of glucosamine sulfate as a disease modifying agent in osteoarthritis. PMID- 1300312 TI - Effectiveness and tolerability of nimesulide in the treatment of osteoarthritic elderly patients. AB - One important point in the treatment of osteoarthritis is to control the pain that accompanies the persistent inflammatory conditions. Because of the chronic nature of the disease, drugs with a good ratio of effectiveness to tolerability must be used. In the following double-blind study the effects of nimesulide, a non-steroidal antiinflammatory drug, were compared with those of placebo in 40 elderly osteoarthritic patients, during and after a treatment cycle of 90 days with two 100-mg tablets a day. The reduction of spontaneous and motion-induced pain and of morning stiffness seen at the various check-ups attested the good effectiveness of nimesulide. Functional status as a whole was improved, and it was found that the concomitant weekly intake of an analgesic (paracetamol) treatment could be decreased during the 3 months of the study. The tolerability of nimesulide was good. PMID- 1300313 TI - In conversation with Eli Edelstein. Interview by David Greenberg. PMID- 1300314 TI - Military psychiatry in Israel: historical review and guiding principles. PMID- 1300315 TI - Psychiatric epidemiology in Israel. AB - Psychiatric epidemiology in Israel began with the inauguration of the Psychiatric Case Register in 1952. Periodic statistical reports by the Ministry of Health Mental Health Services, as well as several Case-Register-based epidemiological studies, have since been published, all of which have related to in-patient data. Community psychiatric surveys have primarily included populations in treatment. The most comprehensive study was carried out on a nationwide basis in 1986 in collaboration with the Nathan Kline Institute. However, only a few community surveys of the general population have been carried out thus far in Israel. The population studied was not nationally representative, and the more advanced screening and diagnostic instruments were not utilized. The necessity for a large scale, multi-centered community survey in Israel, similar to the Epidemiological Catchment Area project in the U.S.A., is suggested. Furthermore, the particular needs of recent and future waves of immigrants must be taken into consideration. PMID- 1300316 TI - A short history of psychoanalysis in Palestine and Israel. PMID- 1300317 TI - A history of biological psychiatry in Israel. PMID- 1300318 TI - Psychiatry and primary medicine. AB - Psychiatry and primary medicine are related to one another for theoretical and practical reasons. The development of this relationship in Israel in recent years is described. Many patients with mental problems are seen by the primary physician only. The most serious cases are usually detected and referred. The main problem is that people with modest mental disturbances are often neither detected nor referred and treated. The development of various forms of communication between psychiatry and primary medicine, such as consultation liaison programs, Balint groups and other methods of training, are described and discussed. PMID- 1300319 TI - Approach to organic psychiatry or the dialogue between brain and mind. AB - This article describes the evolution of concepts of the relationship between brain and mind. Instead of the earlier dualistic approach to mental and brain disorders, we are nowadays confronted with a new approach where the boundaries between these two "worlds" become more and more blurred. PMID- 1300321 TI - Working with practice management consultants. PMID- 1300320 TI - Stereometric evaluation of the enamel-stripping effect of hydrochloric acid. PMID- 1300322 TI - Simplified record keeping for orthotic therapy. PMID- 1300323 TI - Crown inclination relapse with multiflex retainers. PMID- 1300325 TI - Optimal placement of ceramic brackets. PMID- 1300324 TI - Improved patient tolerance with a modified function regulator. PMID- 1300326 TI - Dental practice activities in the state of Alabama. PMID- 1300327 TI - The handpiece sterilization issue. PMID- 1300328 TI - Genetic models for parathyroid tumorigenesis. PMID- 1300329 TI - New actions of parathyroid hormone through its degradation. AB - Parathyroid hormone degradation is intimately connected with its action. By the action of the unique renal neutral cytosolic PTH ase, PTH is split into 1-34 and 35-84 fragments, and further into 35-70 and 71-84 fragments. Amino-terminal 1-34 peptide was found to participate in the autoregulation of PTH secretion, suppressing the intact PTH secretion both in vivo in humans and in vitro in the dispersed bovine parathyroid cells. C-terminal fragment 35-84 and N-terminal fragment 1-34 both suppress the alkaline phosphatase production by ROS 17/2.8 cells to a lesser extent than the intact PTH 1-84, and the sum of the effects of the two fragments approximately equaled that of the intact hormone. Fragments 35 70 and 71-84 were devoid of such activity. Intracellular free calcium of human vascular endothelial cells was raised by intact 1-84, lowered on the contrary by C-terminal 35-84 fragment, but fragments 1-34, 35-70 and 71-84 had no effect. Fragments generated by the actions, supporting the physiological significance of PTH degradation by its target cells. PMID- 1300330 TI - PTH and bone markers of renal osteodystrophy in predialysis chronic renal failure. PMID- 1300331 TI - Magnesium deficiency enhances secretion of parathyroid hormone in normal and 5/6 nephrectomized uremic rats. AB - Hypercalcemia, rather than hypocalcemia, has been observed in conjunction with severe magnesium (Mg) depletion in rat, in contrast to the development of hypocalcemia in Mg deficiency in various animal models. In the present study, a possible involvement of parathyroid hormone (PTH) in the development of hypercalcemia in rat was studied by using a newly-developed sensitive and specific radioimmunoassay system for the determination of rat PTH. In normal rat model, hypercalcemia occurred in association with a decrease of serum phosphate levels in Mg deficiency. However, serum PTH levels were not suppressed despite the occurrence of hypercalcemia, suggesting PTH as an important factor for the development of hypercalcemia. Of interest, in 5/6-nephrectomized uremic model, hypocalcemia, rather than hypercalcemia, was observed in Mg-deficient rats. Serum PTH levels seemed to be higher, but not statistically significant probably due to a small number of rats. However, infusion study clearly demonstrated that PTH secretion was significantly increased in Mg-deficient uremic rats compared with Mg-replete counterparts. The reason for an increase of serum PTH responses might be explained by Mg depletion itself in addition to a fall in serum Ca levels, because infusion study revealed that the magnitude of the stimulation of PTH secretion was increased in Mg deficiency despite the similar degrees of changes in serum Ca levels and that the set point for the suppression of PTH secretion by Ca might be altered in Mg deficiency. Taken these data together, it was strongly suggested that Mg depletion might enhance PTH secretion in rat. PMID- 1300332 TI - Hyperalgesic activity of parathyroid hormone: clinical findings. PMID- 1300333 TI - Incidence, type and severity of psychic symptoms in patients with sporadic primary hyperparathyroidism. PMID- 1300334 TI - Phospholipid transport and parathyroid hormone in epithelial cells. PMID- 1300335 TI - Abnormalities in pancreatic islet function and metabolism in presence and absence of excess PTH: role of high [Ca2+]i. PMID- 1300336 TI - Biochemistry and pathology of PTH-related gene products. PMID- 1300337 TI - Parathyroid hormone and arachidonate metabolism. PMID- 1300338 TI - The non-traditional actions of parathyroid hormone: status 1991, an overview. PMID- 1300340 TI - Actions of parathyroid hormone-related protein as an embryonic differentiation factor. PMID- 1300339 TI - Parathyroid hormone control of intracellular calcium. PMID- 1300341 TI - Osteoblastic control of osteoclast bone resorption in a serum-free co-culture system. Lack of effect of parathyroid hormone. PMID- 1300342 TI - The effect of age on bone and renal responsiveness to parathyroid hormone infusion in man. PMID- 1300343 TI - Chronic renal failure and secondary hyperparathyroidism are responsible for glucose intolerance and impaired insulin secretion of aging. PMID- 1300344 TI - Parathyroid function in hypertension. AB - PHF, secreted by the PTG, induces hypertension by increasing vascular smooth muscle calcium uptake and thereby increasing intracellular calcium levels. PHF secretion is inhibited by dietary calcium and the effects of PHF are blocked by calcium channel antagonists. This explains the paradox whereby both calcium and calcium channel blockers may be effective antihypertensive agents. PHF may be secreted by a specific cell type in the parathyroid gland, numbers of which seem to correlate with PHF levels. Thus, the parathyroid gland does seem to play a role in some forms of hypertension, but this role is probably not due to its production of PTH, but may be related to the secretion of the new factor--PHF. PMID- 1300345 TI - Involvement of parathyroid hormone (PTH) in genetic models of hypertension. AB - Although the precise mechanism(s) of PTH in GHR were not yet fully understood, the research to date is compatible with the presence of a secondary hyperparathyroidism in the GHR models. A low serum ionized calcium level due to renal calcium leak and/or low intestinal absorption of calcium should be the stimulus for PTH hypersecretion. This hypothesis is supported by the fact that both long-term oral calcium supplementation or removal of parathyroid glands prevents and attenuates the development of genetic hypertension. It is concluded that PTH, probably in concomitant with other factors such as vitamin D or parathyroid hypertensive factor, has a permissive effect in the development and the maintenance of hypertension in GHR. PMID- 1300346 TI - Mechanisms underlying elevated [Ca2+]i in brain synaptosomes in states with chronic excess of PTH. PMID- 1300347 TI - Issues related to dust aerosols in the magnesite industry. II. Environmental exposure. AB - Magnesite waste containing largely magnesium oxide (MgO) and a mixture of other metals forms aerosols with a considerable portion of respirable particles when released into the atmosphere. Several animal species (domestic rabbits, Wistar rats, cattle) were used to biologically monitor the accumulation and effects of inhaled magnesite aerosol in two actual locations of the magnesite industry. The study revealed the biological accumulation of magnesium, iron and other metals in the bodies of exposed animals (and F1 animals) as well as specific lesions on tracheal relief, morphological changes in organ microstructure (especially in the lungs, spleen, liver and myocardium), alternations in the reproductive capacity of females, distorted Mg:Ca:P ratio as well as changes in the immune profile. The findings of biological monitoring of animals are consistent with the conclusions of epidemiological studies. PMID- 1300348 TI - Risk of contamination of human and agricultural environment with parasites through reuse of treated municipal wastewater in Riyadh, Saudi Arabia. AB - Two selected sites in the Riyadh metropolitan area were surveyed for the presence of human pathogenic parasites in treated municipal wastewater (TMWW). A total of 100 samples were collected from both sites at two different seasons, the winter and summer reason. The most common parasites seen were the larvae and adult of Strongyloides sp. There were few Ascaris lumbricoides ova, some of which were embryonated and possibly infective, while the highest frequency of Ascaris ova (100 +/litre) was found at site 2 h, the highest frequency of Strongyloides sp. larvae (36-72/litre) and Strongyloides sp. adult (100 +/litre) were found at sites 2 W and 1 W respectively. The variation between sites and seasonal fluctuations showed a significant difference in parasite per litre. High atmospheric temperatures in the Riyadh area seem to be lethal to most intestinal pathogens similarly the absence of protozoal cysts in the TMWW could be attributed to certain treatment processes and other environmental factors. Data obtained from this study will be valuable in planning for the control of parasitic diseases in particular and public health pathogens in general. PMID- 1300349 TI - Fungi associated with stored unprocessed cowpea and groundnut varieties available in Borno State, Nigeria. AB - Five stored unprocessed cowpea (Vigna spp) and four groundnut (Arachis hypogeae) varieties available in Borno State were examined for the mould flora. The degree of infestation of the grains ranged from 31% to 100% and 68% to 86% for surface sterilized cowpea and groundnut respectively. The mould flora commonly encountered were species of the genera Aspergillus. Penicillium species, Scopulariopsis species and Trichoderma species were also found. The flora of the cowpea was dominated by Aspergillus niger while Aspergillus flavus was the dominant mould on groundnut. PMID- 1300350 TI - Efficacy of praziquantel treatment of schistosomiasis in a non-endemic country: a follow-up of parasitological, clinical and immunological parameters. AB - Schistosomiasis patients were immigrants to Czechoslovakia from Angola and Yemen. Most of them had light or moderate infections and felt subjectively healthy. They received treatment with praziquantel (two doses with a total of 40 mg/kg) and were followed up for several years. In nine of 13 patients, Schistosoma haematobium or S. mansoni eggs with undamaged miracidia were detected in biopsies from the bladder or the rectum one year or later after treatment. Granulomatous reactions in the rectum and bladder lesions of stage 1 including thickened bladder walls persisted in most of the patients. Antibody levels against adult S. mansoni worm antigen remained elevated for at least two years after therapy in some patients and declined in others. Among the nine patients, for whom pre- and post-treatment sera were available, the changes in relative levels of antibodies did not strictly correlate with the continued presence of schistosome eggs in, or their absence from, biopsies. We discuss the results obtained with sensitive diagnostic techniques in the absence of subjectively perceived disease. PMID- 1300351 TI - Diagnostic laboratory parasitology--a stepping stone to medical research in tropical Africa. AB - African countries can concentrate mainly on operational and problem-solving type of medical research using as a basis routine diagnostic laboratory parasitology which can be elevated to research level by incorporating all relevant techniques backed by statistically-based programming. Because of high incidence of parasitic infections and the peculiar host-parasite relationship, co-operation between all departments of any major hospital will be required to deal with the diseases due to them. Longitudinal studies on some parasites will enable generalisation and specific views to be formed on some infections. Multiplicity and wide variety of available techniques offer several research possibilities of clinico-pathological and epidemiological significance. Routine laboratory-based research offers the right environment for training various types of laboratory workers from technicians to medical parasitologists, through on-the-job training on techniques, investigative studies and research, backed by formal lectures and practicals at various levels. Trainee medical parasitologists can obtain higher degrees locally or abroad. The research can be organised around micro and mini research units. This approach is cost-beneficial because it minimises administrative difficulties and so avoids wastage. The results can be used to monitor impact of national development on parasitic infection prevalence and to formulate a policy on parasitic disease management. PMID- 1300352 TI - Persistence of low levels of Plasmodium falciparum resistance to chloroquine in the autochthonous population of the Central African Republic. AB - In Central African Republic, the first cases of resistant P. falciparum to chloroquine occurred in 1983 in non immune expatriate residents on regular chemoprophylaxis. From 1984 to 1991, 950 in vivo tests with a seven days observation period were performed in semi-immune autochtonous children living in seven towns of the country. Chloroquine treatments were given at 25 mg/kg over 3 days period to children with P. falciparum parasitaemia > 500 (634 simplified methods) or > 1000/mm3 (316 WHO standard field tests), usually asymptomatic. Until 1988, the surveys show an absence or a low frequency of chloroquine resistance (usually below 10%) according to the town; since 1989, the resistance has been present in all towns but everywhere with a frequency under 20%. None cases of R III level resistance was observed and all children became or remained asymptomatic at day 7. Until further surveys demonstrate a decreased efficacity of chloroquine, it is advised that chloroquine be used at 25 mg/kg over 3 days period as the treatment of choice in uncomplicated acute malaria in the Central African Republic. PMID- 1300354 TI - Weight loss, total and differential leucocytic counts in mice treated with alcohol during Ancylostoma caninum infection. AB - Females of Swiss albino mice were treated with various doses of alcohol and Ancylostoma caninum larvae. Mice which received 40% alcohol for 20 days showed a significant decrease in body weight and in the number of leucocytes. Eosinophilia was also observed in mice which were treated with 40% alcohol for 20 days. PMID- 1300353 TI - Non-ocular clinical onchocerciasis in relation to skin microfilaria in the Taraba River Valley, Nigeria. AB - Examination of 2,876 persons in fourteen communities was carried out for clinical onchocerciasis on the Taraba river valley, Nigeria, where parasitological findings indicate unusually high endemicity. Forty-five percent of the population had at least one type of skin lesion or the other, the commonest of which was pruritus. Thirty-two percent had nodules. Some of the nodules were located in unusual sites such as the mammae, anus. Nodule carriage and nodule-load as well as lymphatic enlargement were higher than those recorded elsewhere in Nigeria and tended to increase with increase in age. When subjected to regression analysis, the relationship between skin lesion, nodule carrier rate, nodule load, scrotal enlargement and microfilaria rate (mf) on one hand and microfilaria density (mfd) on the other showed a near-perfect correlation. The findings of this study suggest that certain clinical manifestations of onchocerciasis may be a reliable and more rapid alternative to the parasitological approach in the assessment of the prevalence and severity of the disease in communities with similar socioecological characteristics. PMID- 1300355 TI - Cryptosporidiosis in young children suffering from diarrhoea in Riyadh, Saudi Arabia. AB - A one-year study of patients (0-120 months of age) with diarrhoea at King Abdel Aziz University Hospital (KAUH) in Riyadh, Saudi Arabia, detected two cases of cryptosporidiosis. Stool specimens from 174 children with diarrhoea and negative for other parasitic infection were examined using a safranin-methylene blue stain (S-MB). Two children (L.1%) were showing Cryptosporidium oocysts. None of 50 control children who did not have diarrhoea and was free of Giardia lamblia was Cryptosporidium positive. PMID- 1300356 TI - Hydrolytic enzymes in leprosy sera. AB - Serum samples collected from 45 untreated leprosy patients and 10 healthy subjects were studied for the activities of alkaline phosphatase, N-acetyl beta glucosaminidase and beta-glucuronidase. A highly significant increase in the specific activity of these enzymes was observed in all types of leprosy patients as compared to controls. Increase in the level of circulatory hydrolytic enzymes could be a tissue damaging factor and may be responsible for many of the lesions seen in leprosy. PMID- 1300357 TI - Release of acid hydrolases in spectrum of human leprosy. AB - Release of acid hydrolases by blood monocytes (BM) of leprosy patients both before and after 6 months of chemotherapy was measured fluorimetrically. Monocyte cultures were set up for spontaneous as well as zymosan dependent enzyme release measured after 2 hrs and 24 hrs of culture. In the untreated multibacillary group (BL/LL) a significantly higher (P < 0.001) release of both B-glucuronidase (BG) and N-acetyl glucosaminidase (NAG) was observed compared to the paucibacillary group (BT/TT) and healthy controls. On comparing the BT/TT group with controls a significant decrease (P < 0.001) in zymosan dependent NAG release was observed in the former group at 2 hrs culture. After 6 months of antileprosy therapy, a significant decrease (P < 0.05) in BG release was observed from BM of multibacillary patients, whereas NAG activity increased significantly (P < 0.05) in the paucibacillary group compared to the controls. The results of the present study suggest that non-oxidative metabolic status of BM vary within the leprosy spectrum. PMID- 1300358 TI - Penicillinase-producing Neisseria gonorrhoeae conjunctivitis on some Nigerian children. AB - During 21 month study of bacterial conjunctivitis among 121 children in two health care centres in Calabar, Nigeria, a total of 90 (74.4%) cases were culturally confirmed. Neonates had the highest age-specific attack rates with 48 (53.3%) cases. Neisseria gonorrhoeae, the predominant pathogen, was recovered from 32 (35.6%) infections; 21 (65.6%) of them from neonates. Cultures of genital swabs of consenting parents of infected neonates as well as those of three female children aged 2-12 years with concurrent vulvo-vaginitis yielded N. gonorrhoeae. Younger women, mostly primi-gravidae were more frequently found to have benefited from peri-natal health care services than older multi-gravidae. Nevertheless, such access to health care services did not appear to influence the frequency of gonococcal conjunctivitis in neonates from the two maternal groups (P < 0.01). Sexual abuse and contaminated fomites were the possible modes of gonococcal infection transmission to older children. Overall, 22 (68.8%) strains of gonococci were resistant to penicillin; 19 (59.4%) were penicillinase-producing Neisseria gonorrhoeae (PPNG), while 5 (15.6%) had chromosomally-mediated resistance. All isolates were sensitive to erythromycin. This study recommends a review of gonorrhoea surveillance in pregnancy to include routine examination of cervical swabs just before delivery. PMID- 1300359 TI - Pilot studies on the occurrence of some infectious diseases in two different areas in south Yemen (Aden) (part II. Microbiology). AB - This paper is the second part of the article dealing with intestinal bacteria. The findings are relatively poor in comparing with the frequency of intestinal protozoa. Among 83 stool specimens taken for bacteriological examination 14 isolations of different bacteria were proved. One S. muenchen was isolated from a 3 year old boy with fever, diarrhoea. Five cases of Alkalescens dispar 05 manit negative and 05 manit positive were identified. Two of these cases were without clinical symptoms. All were males aged 10-17 years. One isolation of E. coli EPEC 086 K6 H11 was in a 10 year-old boy with diarrhoea, four watery stools daily and cramps. Six cases of other E. coli were of different types, all with clinical symptoms. Of them three were males and three females at the age from 3-46 years. One case had a mixed infection of Citrobacter, E. coli and Klebsiella with diarrhoea, about 5 watery stools daily and abdominal pain. The frequency of intestinal bacteria in males was nearly three times higher than in females. The occurrence in age groups 10-20 was almost equal 20.0-22.2%, in 0-4 it was 42.9% and surprisingly low in 5-9 years old--3.4% only. PMID- 1300360 TI - Treatment of nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma is a common cancer among Thai males. When first seen, the disease is almost always locoregional. Evaluation of the tumor volume at the nasopharynx by computerized axial tomogram must be done prior to therapy. Treatment is done by radiation therapy to the nasopharynx and cervical lymph nodes, and is effective. Chemotherapy has high activity in this disease. However, more studies are needed to define its role. Side effects of treatment are radiation related, and confined to the area of previous radiation. They can be minimized if the patients strictly adhere to the physician's advice. Causes of treatment failure and death can be due to both locoregional failure and distant metastasis, notably to bone, liver and lungs. PMID- 1300361 TI - Maternal risk factors for low birth weight newborn in Thailand. AB - The present study assesses the risk approach for maternal risk factors for LBW newborn in Thailand. This study can be considered as a managerial tool for developing local strategies and is particularly useful in the field of maternal and child health care. A summary of maternal risk factors for LBW newborn as listed in Table 7 and can be used as a health educational tool for pregnant women and as basic data for marital counseling. It can also be used to keep the public informed about the maternal risk factors for LBW newborn which will help Thai women of reproductive age avoid the chance of having such babies. PMID- 1300362 TI - Risk factors for neural deficit in spinal tuberculosis. AB - From 1975 through 1989, retrospective study of 155 patients with spinal tuberculosis was carried out at Ramathibodi Hospital to study predisposing factors to neural deficit and results of treatment. Two groups of patients who had no neural deficit and had neural deficit were compared. Clinical characteristics of the patients between the two study groups were similar with regard to sex, duration of symptoms, number of vertebrae involved, angle of gibbus deformity and erythrocyte sedimentation rate. There were statistical differences in age, cephalad level of infection, loss of vertebral body and clinical evidence of cold abscess. For patients with neural deficit, the results generally are good with anterior decompression and stabilization. PMID- 1300363 TI - Incidence of cholelithiasis in the northern part of Thailand. AB - It may be concluded from comparisons of recent u/s examinations in Northern Thailand to studies in Japan and to the gallstone study conducted over two decades ago that gallstone disease in Thailand is starting to exhibit the same situation as in the West. In comparing overall rates over time the gallstone incidence in Thailand appears to have climbed from 2.61 to 3.10 per cent (Fig. F). The rate increase is even more significant when broken down by sex (male: 1.89%--> 2.50%, female: 3.23%--> 3.70%). In addition, the present rates of female and male gallstone incidence in Northern Thailand closely match the rates found in studies of the Japanese population. Because gallstone disease has become a major public health problem in the West, a number of studies have emphasized the epidemiological characteristics of the disease in order to implement controls. As Thailand's gallstone problem seems to be heading towards the same level of importance further studies involving epidemiological factor linkage may be necessary and the technological advances in Ultrasonography make such studies quite feasible. PMID- 1300364 TI - A study of unit cost of routine investigations in Srinagarind Hospital. AB - We have used the step up allocation accounting method to determine the actual costs of complete blood count, urinalysis, chest radiograph and electrocardiogram. We found that the actual costs were quite different from the price set up by the hospital. The actual cost were much higher than the price for the complete blood count and urinalysis and much lower for the chest radiographs and especially for electrocardiogram. We propose that in performing economic analysis involving all these investigations, the actual cost should be used instead of the price. PMID- 1300365 TI - Decreased suppressor T-lymphocytes in women who received progestogen injections. AB - Decreased levels of suppressor T-cells (CD8+) were found in 17 normal women who received progestogen (Depoprovera) injection, 150 mg intramuscularly every three months for contraceptive purposes, for more than 30 months. The helper: suppressor T-cells (CD4+ : CD8+ ratio) was significantly elevated in this group compared to 30 normal female controls. No significant change of T-lymphocyte was found in 53 normal women who received the injection for less than 30 months or who received combined oral contraceptive pills. In conclusion, long term progestogen injection induced a lowering of suppressor T-cell levels, which is the same immunological change found in several autoimmune diseases. PMID- 1300366 TI - Biparietal diameter/femur length ratio and actual femur length/expected femur length ratio: a sonographic screening method for Down's syndrome. AB - Several ultrasonographic signs have been described in second-trimester Down's syndrome fetuses. Previously published reports have shown that fetuses affected with Down's syndrome have normal biparietal diameter (BPD), high BPD-to-femur length (FL) ratio, and low actual FL-to-expected FL ratio. A retrospective comparison of the BPD-to-FL ratio and actual FL-to-expected FL ratio was made between 3 fetuses with Down's syndrome diagnosed prenatally by second-trimester amniocentesis and 189 normal fetuses with gestational age varying from 13-25 weeks who were seen in the Ultrasound Unit of Department of Obstetrics & Gynaecology, Chulalongkorn Hospital between January 1, 1989 and May 31, 1990. The sensitivity of BPD-to-FL ratio and actual FL-to-expected FL ratio as a screening technique for Down's syndrome in this study was 66.7 and 100 per cent, with a specificity of 93.4 and 89.2 per cent respectively. These sonographic parameters appear to be a useful screening method for Down's syndrome. PMID- 1300367 TI - Late ulnar nerve injury following Kirschner wires fixation of the supracondylar fracture of the humerus. AB - Most supracondylar fractures of the humerus can be treated by closed methods. Open reduction and internal fixation by wires or pins are indicated in a difficult fracture (Kekomaki et al 1984) or in vascular injury following the fracture. This fixation should be temporary and removed immediately upon obtaining the desired purpose. To increase surgeons awareness of inadvertently leaving the implant for too long, we are reporting an unusual complication of migration of the Kirschner wire resulting in late ulnar nerve injury. PMID- 1300368 TI - Antimicrobial resistance and immunosuppression. PMID- 1300369 TI - Cancers in immunocompromised hosts. PMID- 1300370 TI - Immunotoxicology and conventional toxicology. PMID- 1300371 TI - Specific methods to evaluate the immune system. Functional assays. PMID- 1300372 TI - Immunosuppression: current strategies. PMID- 1300373 TI - Validation: state of the art United States National Toxicology Program & Fischer 344 rat cyclosporine--a study. PMID- 1300374 TI - Iatrogenic immunodeficiencies. PMID- 1300375 TI - In vitro immunotoxicology. PMID- 1300376 TI - Current status and perspectives for the regulatory requirements in immunotoxicology. PMID- 1300377 TI - Characteristics of laser Doppler flowmeters with differing optical arrangements. AB - Recently, various laser Doppler flowmeter (LDF) systems have been used for evaluation of tissue microcirculation. However, indifference has often been shown by doctors and researchers regarding their sampling volume, stability and accuracy, which differ with various optical arrangements. In this study we evaluated the characteristics of three LDF systems with different optical arrangements. The sampling depths in both blood and tissue were found to differ with the different optical arrangements, although the laser power emitted from the probes is nearly equivalent. Each depth significantly changed at haematocrits between 5.0 and 36.5%. The stability and the accuracy of the measurements also differed. In the practical case of tissue microcirculation it is important to measure blood flow with an understanding of the material differences in the characteristics of the LDF systems. PMID- 1300378 TI - A picture communicator for symbol users and/or speech-impaired people. AB - There are several approaches to producing communication aids for people with disabilities. The system described here takes the approach of utilizing as much mainstream hardware as possible, and adapting it with some modular software tools which have been designed to facilitate the building of customized symbol communication systems. The target audience are clients who are symbol users and/or have a speech impairment. The system provides several levels of screens, each of which can contain grids of scalable icons. A number of input methods are provided including keyboard, switch, mouse and touch-screen. Digitized and/or text to speech synthesis can be used for reinforcement of selections and for communication. The structure of the system is discussed and initial feedback from the first field trials is presented. PMID- 1300379 TI - Microwave thawing of biological materials using a cylindrical rotational mixing system: a calibration model. AB - A cylindrical device is described for placement within a domestic microwave oven, in order to achieve rapid thawing of biological materials, including plasma, located within the cylinder. The device is economical to fabricate within standard workshop facilities. It secures uniform microwave exposure and continuous mixing of material by rotation of the cylinder in two planes, entraining the motion of the oven drive spindle by a very simple system of frictional gears. Data are presented on the accuracy of this system, and on some important points relating to its use both as a calibration model and a research tool. Such research may eventually enable this system to provide a cheap and reliable option for thawing therapeutic materials for clinical use. PMID- 1300380 TI - [Proceedings of the 65th annual meeting of Japan Association of Industrial Health]. PMID- 1300381 TI - [Fatigue of workers in computerized offices]. PMID- 1300382 TI - [Life and fatigue of the shiftworkers with two days off in the weekend]. PMID- 1300383 TI - [Cervicobrachial and low back disorders]. PMID- 1300384 TI - [Strategy for reducing fatigue in women workers]. PMID- 1300385 TI - [Occupational fatigue in semiconductor and advanced-technology industry]. PMID- 1300386 TI - [Trends of international research work on immune toxicology and occupational allergy]. PMID- 1300387 TI - [Occupational allergy and immunological toxicology--special reference to respiratory diseases]. PMID- 1300388 TI - [Occupational allergy and immunologic toxicology--special reference to skin diseases]. PMID- 1300389 TI - [Evaluation of allergic reaction and setting for occupational exposure limits]. PMID- 1300390 TI - [Study of occupational allergy and immunologic toxicology from a standpoint of control for actual occupational health]. PMID- 1300392 TI - [The state of corneal endothelium after cataract extraction as examined by contact endothelial microscopy]. AB - The central area of the corneal endothelium was examined in 130 patients after an intracapsular extraction of a senile cataract without implantation of an intraocular artificial lens, with implantation of an anterior chamber artificial lens and after an extracapsular extraction of senile cataract with implantation of a posterior chamber artificial lens. The authors used the endothelial contact microscope Copper Vision with an endothelial cell counter from MLC Technologies. The mean proportional loss of the corneal endothelial cells for the 1st group after 1 month amounted 11.6%, after 6 months from operation 13.0%; for the 2nd group after the 1st month 15.0%; for the 3d group after 1 month 13.5% and after 6 months 17.0%. PMID- 1300391 TI - [Study on the influence of silicone oils of various viscosities on anterior eye structures]. AB - Intraocular silicone oil tamponade plays important role in the treatment of complicated retinal detachments. Aim of present study was an investigation of the effects of different silicone oil fluids on the anterior chamber structures. Standard silicone oils with 100, 990, 3690 mPa.s viscosity and highly purified silicone oil with viscosity 5000 mPa.s were used. Corneal silicone oil impregnation was observed in corneas which were in contact with silicone oil with 100 mPa.s. viscosity. Silicone oil impregnation of uveal structures was observed in all cases after the 4 months follow-up. "Posterior collagenous layer" was observed subendothelial in eyes injected with various silicone oil fluids including highly purified one. Results of our investigation show that use of highly purified silicone oil does not allow to reduce the side effects on ocular structures caused by emulsification or a barrier to the nutrition and exchange of products of metabolism provided by silicone oil bubble. PMID- 1300393 TI - [Spontaneous Pulfrich's effect in patients with dysfunction of the optic nerve]. AB - Twenty patients with various dysfunctions of the optic nerve were subjected to examinations by means of a test based on the Pulfrich's phenomenon. The Pulfrich's effect was observed in 18 among them. The survey of the phenomenon was continued in 5 patients in the course of the treatment. It was detected that the dimension of the spontaneous Pulfrich's illusion diminishes gradually tending towards norm. The results obtained assure us of the usefulness of the application of the Pulfrich's effect as a diagnostic test in ophthalmology and neurology. PMID- 1300394 TI - [Morphology of changes in records of visual evoked potentials in patients with multiple sclerosis]. AB - Statistical analysis of the parameters of the waves of visual evoked potentials were performed in 2 groups: in 32 patients with a sure diagnosis and in 21 with a probable diagnosis of multiple sclerosis. In the 1st group prevailed the reduced record with a delayed latency of peaks of the A, B, C waves and with the interhemispherical and interocular asymmetry of the diagram. In the 2nd group dominated an delayed latency of the B and C waves and interhemispherical asymmetry of those waves. Abnormal characteristic of the record was obtained also after stimulation of the eyes of the examined patients with a full visual acuity. PMID- 1300395 TI - [Ocular symptoms in internal carotid artery occlusion]. AB - The internal carotid artery occlusion causing an insufficiency of the cerebral circulation manifests itself--besides the neurological symptoms--by disorders of the visual organ. One can distinguish among them early, functional symptoms in the form of transient unilateral hemianopia on the side opposite to the occluded carotid artery and the attacks of transient amblyopia. Signs of fixed ischaemia of the eye ball appear afterwards in the form of oculomotor and pupillary disturbances, neovascularization of the iris, disturbances of the IOP, central retinal artery occlusion, ischaemic optic atrophy. The authors emphasize the value of Doppler's diagnostic ultrasonography, a fast and non-invasive method of direct evaluation of the blood flow in the internal carotid artery system. PMID- 1300396 TI - [Prognostic value of treatment trials used during the preoperative period in patients with primary retinal detachment]. AB - Analysed are the results of surgical treatment and the methods applied in patients with primary retinal detachment who have been placed in recumbent position in the preoperative period. It was demonstrated that in all the cases in which after staying in bed one could observe a full or partial retinal re apposition--a relatively simple and sparing operation was sufficient for a lasting cure. The presented results show that a successful outcome of the reclining position trial constitutes one of the favourable prognostic factors for the success of the surgical intervention. PMID- 1300397 TI - [Use of photocoagulation during surgery for retinal detachment]. AB - On the basis of a 10-years clinical material comprising 95 eyes operated for retinal detachment in the Department of Ophthalmology in Krakow the authors evaluated the usefulness of xenon and laser coagulation as a method complementing the blockade of the retinal holes. It had been used in 18 p.c. of all operated eyes attaining in this group of cases the re-apposition of the retina in 61 p.c. The efficacy of the coagulation depended on the adherence of the retina and showed itself as formation during the surgery of visible foci and the development of a distinct, pigmented scar. There were no complications connected with photocoagulation as well the xenon as the laser one; all this encourages to employ both these methods. PMID- 1300398 TI - [Probability of successful operation in very severe retinal detachment using scleral buckling procedure]. AB - The aim of this study was to study the efficacy of operation of scleral invagination in the treatment of very severe retinal detachment with proliferative vitreoretinopathy (PVR). The investigations comprised 36 eyes operated in the Department of Ophthalmology in Krakow in the period 1986-1990. The authors performed in 24 patients a encircling operation with a silicone band, in 12-meridional or parallel extrascleral silicone sponge implants. Reattachment of the retina was achieved in 58 p.c. of eyes and an improvement of the visual acuity in 47 p.c. The performed analysis showed a substantial dependence of the attained effect of surgery on the grade of advancement of the PVR; it enabled to ascertain that the limit of possibilities of the scleral buckling procedure determines PVR stadium C3. PMID- 1300399 TI - [Evaluation of the usefulness of vitrectomy in the treatment of proliferative diabetic retinopathy]. AB - The authors analyse the results of 146 operations of vitrectomy through the pars plana executed in cases of complications of diabetic retinopathy. In 50 eyes with prognostically very severe conditions (tractional retinal detachment, presence of central retinal holes, recurrent intraocular haemorrhages) vitrectomy was connected with an intra-bulbar injection of silicone oil. In the period of 6 months to 3 years after surgery the improvement of the visual acuity was attained in 96 eyes (66 p.c.). Intravitreal injection of the silicone oil increased the chance of reattachment of the retina and reduced the incidence of a postsurgical recurrent intraocular haemorrhage. PMID- 1300400 TI - [Evaluation of the use of excimer laser in the treatment of keratitis and pterygium]. AB - Excimer laser was used for the treatment of 67 eyes with keratitis and 15 eyes with corneal ulceration. Also by means of excimer laser 18 eyes were treated for pterygium; cure was observed in 17 cases. The observation period was 6 months. PMID- 1300401 TI - [Use of a new model of keratoprosthesis made from carbon in treatment of dense leukoma after ocular burns]. AB - Discussed are the results of kerato-prosthetics in 12 cases of severe post-burn leukoma by means of a new model of keratoprosthesis with a carbon bearing. The material for construction of the carrier part of the prosthesis is based on carbon fibres and Polish technology worked up by the Institute of Material Engineering of the Mining-Metallurgic Academy in Krakow. PMID- 1300402 TI - [Lamellar keratoplasty in treatment of recurrent pterygium]. AB - Presented are 4 cases of recurrent pterygium treated by lamellar keratoplasty. The surgical technique and the results of the treatment are described. PMID- 1300403 TI - [Penetrating keratoplasty in post-burn corneal leukoma in personal material]. AB - The authors present the surgical technique and the results of treatment of 12 patients with corneal leukoma caused by scalding. In all the cases they performed a perforating keratoplasty. Two years after operation among 7 grafts 5 were transparent. Perforating grafts in leukoma caused by a chemical burn have poor prognosis in contrary to thermic burns. PMID- 1300404 TI - [Bilateral Purtscher's syndrome]. AB - Purtscher's syndrome (traumatic retinal angiopathy, posttraumatic retinopathy) belongs to rare posttraumatic retinopathies. The authors present a case of a bilateral occurrence of this syndrome after a head injury connected with pancreatitis. A 6-months long observation of the patient showed an improvement of the visual acuity from counting fingers to 0.1 and receding of the inflammatory oedematous changes at the eye fundus; there remained a pallor of the temporal side of the optic discs. PMID- 1300405 TI - [Unilateral exophthalmos during the course of epidural hematoma]. AB - Based on 10 cases in the literature and one of our own a review is made on the occurrence of an association of an intracranial epidural haematoma with unilateral exophthalmos. The possible pathogenesis of this infrequent phenomenon is discussed. PMID- 1300406 TI - [Necrotizing scleritis--successful treatment with solcoseryl]. AB - A case of the patient with necrotising scleritis in osseous rheumatism is presented. The patient was treated with Solcoseryl injected intravenously. During the 20-days treatment, the drug has been tolerated well. It speeded the healing of the sclera which prevented secondary complications and made it possible to maintain the eye's visual ability. PMID- 1300407 TI - [What is the visual field?]. AB - Eye movements were recorded in the course of visual field determination. The behaviour of the eye is various in different persons, defying any rule, except, contrary to the definition of the visual field, it does not remain immobile but executes one or more saccades. Discussing the results the authors present a new concept of the visual field. PMID- 1300409 TI - The biocultural approach in nutritional anthropology: case studies of malnutrition in Mali. AB - Socioeconomic status is often cited as the most important factor influencing nutritional status and growth in children. Research in Mali, however, has shown that relative poverty is not an accurate predictor of nutritional status and growth, and that other factors may be more important. In Mali, these factors include maternal age, marital problems, untreated illness, allocation of household resources, maternal attitudes, maternal competence, support networks, and the social structure of a polygynous, patrilineal society. In this paper, case studies of children in three families illustrate how sociocultural malnutrition in young children can be viewed as an unintended consequence of the complex interactions among these factors. PMID- 1300408 TI - The use of ethnography and structured observations in the study of risk factors for the transmission of diarrhea in highland Papua New Guinea. AB - Methods that combine anthropological and epidemiological data are needed for the study of behavioral risk factors in communicable diseases, but as yet remain undeveloped. Ethnography is often undervalued as both the preliminary and integrative step in the design and execution of such studies. The analysis of critical methodological issues emerging from a case-control study of the behavioral and environmental risk factors for the transmission of childhood diarrhea in both urban and rural highland Papua New Guinea suggests that focused ethnographic assessments, complemented by structured observations performed by nonprofessionals, may provide a viable research design. In highland Papua New Guinea, significant risk factors include non-usage of latrines and sleeping with pigs; the latter is a factor that could have important implications regarding women's roles in a changing economy. PMID- 1300410 TI - Symbolic mediation and commoditization: a critical examination of alcohol use among the Haya of Bukoba, Tanzania. AB - Low-alcohol-content fermented beverages are thoroughly enmeshed in the social, economic, commensal, and cosmological spheres of life among most peoples of sub Saharan Africa. This paper describes and analyzes the role of alcoholic beverages as symbolic mediators and commodities among the Haya of northwest Tanzania. Data gathered during field research in 1985-86 are employed to describe the ways in which the Haya portray excessive drinking and the indigenous strategies they use to address frequent drunkenness when it is perceived as a health problem. A central feature of the paper contrasts the role of a cultural schema of four levels of intoxication in processes of symbolic mediation and commoditization, thereby contributing to critical medical anthropological analysis. PMID- 1300411 TI - The biological impact of social responses to the AIDS epidemic. AB - This paper examines the extent to which social responses to the AIDS epidemic contribute to the continued transmission of the virus, thereby exacerbating the biological impact of the epidemic. Following the model of McGrath (1991), social responses to AIDS are examined in terms of their impact on potential transmission of HIV. Responses are evaluated using established criteria for decreasing disease transmission: eliminating the source of infection, eliminating contact necessary for infection, decreasing susceptibility of hosts, or decreasing the infectivity of infectious persons. The most frequent responses to AIDS have been scapegoating, resulting in ostracism, stigma, and blame; resignation; use of alternative therapies; political mobilization; and research. With the exception of political mobilization in some communities, the social responses to AIDS have not decreased the biological impact of the epidemic, and, therefore, may not be "biologically appropriate". PMID- 1300412 TI - Garbage imperialism: health implications of dumping hazardous wastes in Third World countries. AB - This paper calls for studies of the potential health implications of today's hazardous waste disposal practices, and suggests that such studies are urgently needed in Third World countries where industrial nations are increasingly dumping their unwanted waste materials. The United States produces enormous quantities of hazardous waste each year, and approximately 1,200 "priority hazardous waste sites" presently threaten the nation's health. Because of environmental regulations, landfill closings, and citizen opposition to local waste facilities, industrialized countries are increasingly disposing of their problematic materials by shipping them to the Third World, where they pose substantial threats to human health and the environment. From a political economy perspective, this paper suggests that global health would be better served by reducing hazardous waste production, encouraging reusing and recycling, and restricting or banning international shipment of toxic wastes. PMID- 1300413 TI - HIV testing in the health care setting: a case review. PMID- 1300414 TI - Delivery of home hemodialysis care in the 1990s: issues and alternatives. Part III. PMID- 1300415 TI - Home hemodialysis: a valid choice. PMID- 1300416 TI - Unresolved malnutrition of the dialysis patient: is supplementation enough? PMID- 1300417 TI - NRAA president sees ProPAC as key focus in '93. PMID- 1300418 TI - Lessons from Japan can go beyond building automobiles. PMID- 1300420 TI - Finding the real meaning of "managed care" for the ESRD community. PMID- 1300419 TI - HIV investigation seemed to be a "hoax". PMID- 1300421 TI - Outcome-related reimbursement will not improve patient care. PMID- 1300423 TI - NKF proposal tied outcome to reimbursement. PMID- 1300422 TI - Nursing's role crucial in the future of managed care. PMID- 1300424 TI - Cause & effect, or ... there are lies, damn lies, and statistics. PMID- 1300425 TI - Home hemodialysis: a view from Seattle. PMID- 1300426 TI - The future of HHD lies in the hands of the renal community. PMID- 1300428 TI - Home hemodialysis: well worth the hard work. PMID- 1300427 TI - With the right population, HHD means better dialysis, outcome. PMID- 1300429 TI - The value of nutritional intervention for the pregnant patient with chronic renal insufficiency. PMID- 1300430 TI - Dialysis treatment: are patients aware of their options? PMID- 1300431 TI - Can a "fishbone" prevent peritonitis? PMID- 1300432 TI - Primary IgA nephropathy: the relevance of experimental models in the understanding of human disease. AB - IgA nephropathy is the most common form of primary glomerulonephritis worldwide. About one quarter of patients progress to terminal renal failure 10 years after the apparent clinical onset. Therefore, the disease represents a social problem in terms of number of patients requiring maintenance hemodialysis. Despite the intense research effort devolved to clarify the pathogenesis of IgA nephropathy, the exact relationship linking the several factors involved is still unknown. In this review we analyze the experimental works reported since 1979, when the first animal model of IgA nephropathy was published by Rifai et al. We also discuss the interplay between experimental data and clinical observations to maximize the information gathered from the different animal models. Finally, we report the new insights into the role played by cytokines, growth factors and autacoids. PMID- 1300433 TI - Very late activation-3 integrin is the dominant beta 1-integrin on the glomerular capillary wall: an immunofluorescence study in nephrotic syndrome. AB - The expression of alpha 2; alpha 3; alpha 5; alpha 6-subunits of the beta 1 [very late activation (VLA)] integrin family was studied in kidney specimens using an immunofluorescent technique. 6 specimens from normal kidney were compared with 10 specimens from patients affected by various glomerulopathies [minimal change nephropathy (MCN), membranous nephropathy (MN) and systemic lupus erythematosus nephritis (SLEN)]. On normal glomeruli, alpha 3 was the dominant integrin, being mainly present on podocytes and showing a linear fluorescent pattern codistributed with laminin. In MCN and SLEN, alpha 3 presented a normal pattern. In MN, alpha 3 revealed a trabecular picture on thickened glomerular basement membranes. Moreover, in stage-III MN, a segmental loss of alpha 3-integrin was detected. In our opinion, VLA-3 may offer an interesting approach to the study of the relationships between podocytes and their substrate. PMID- 1300434 TI - Treatment of hyperlipidemic kidney graft recipients with lovastatin: effect on LDL-cholesterol and lipoprotein (a). AB - An increased incidence of hyperlipidemia places kidney graft recipients at increased risk for cardiovascular disease and may contribute to a decline in graft function. A study was undertaken to evaluate the safety and efficacy of lovastatin in these patients. Twelve kidney graft recipients with stable graft function and a cholesterol (chol) level over 250 mg/dl (6.46 mmol/l) were included. The lipid-lowering treatment consisted of 20 mg lovastatin daily, and all patients received immunosuppression with ciclosporin (CS) and prednisolone. Total chol decreased by 27% (300 +/- 56 to 219 +/- 28 mg/dl; 7.76 +/- 1.45 to 5.66 +/- 0.72 mmol/l; p < 0.01), LDL-chol by 35% (220 +/- 38 to 143 +/- 17 mg/dl; 5.69 +/- 0.98 to 3.70 +/- 0.44 mmol/l; p < 0.01) and triglycerides by 33% (207 +/ 127 to 138 +/- 56 mg/dl; 2.36 +/- 1.44 to 1.57 +/- 0.64 mmol/l; p < 0.05). HDL chol increased by 10% (57 +/- 11 to 63 +/- 13 mg/dl; 1.47 +/- 0.28 to 1.63 +/- 0.34 mmol/l; NS). The ratio of total chol/HDL-chol, a generally accepted risk predictor of atherosclerosis, fell from 5.4 +/- 1.3 to 3.3 +/- 1.2, p < 0.01. Lipoprotein (a) [lp(a)], an independent risk predictor for atherosclerosis, was also evaluated at baseline and after 6 months of lovastatin treatment and showed a decrease of 39% (32.9 +/- 27.6 to 19.9 +/- 22.9 mg/dl; 0.85 +/- 0.71 to 0.51 +/ 0.59 mmol/l; p < 0.05). No adverse side effects were seen at this dosage, and hepatic and renal parameters remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300435 TI - 25-Hydroxyvitamin D3 metabolism in vitro by mononuclear cells from hemodialysis patients. AB - Hemodialysis patients have a capacity for extrarenal production of 1 alpha,25 dihydroxyvitamin D3 [1,25(OH)2D3]; however, the source of the hormone is unknown in these patients. Since 1,25(OH)2D3 synthesis by cultured hematopoietic cells has been demonstrated previously, we assessed hormone production by mononuclear cells from peripheral blood obtained from normal subjects (n = 6), uremic patients not yet requiring dialysis (n = 4) and hemodialysis patients (n = 14). 1,25(OH)2D3 production was analyzed by sequential straight phase and reverse phase HPLC. In the hemodialysis group, the mean specific production of a metabolite co-eluting with 1,25(OH)2D3 (in fmol/100,000 cells/h) both by monocyte enriched adherent cells (Mo) and lymphocyte-enriched non-adherent cells (Ly) was increased as compared to non-dialyzed subjects (119 vs. 22 for Mo, not significant, 65 vs. 14 for Ly, p < 0.05). Taken together, Mo and Ly from hemodialysis patients synthesized significantly more 1,25(OH)2D3 (p < 0.02) than non-dialyzed subjects (184 vs. 36, means). No differences were found between cells from normal subjects and patients with preterminal renal failure. Exposure of cultured normal Mo (n = 6) to cuprophane (CU), polyacrylonitrile (AN69) or polycarbonate-polyether (PC) membrane devices resulted in increased 1,25(OH)2D3 production as compared to control incubations without membrane. The rank order of increase was PC > AN69 > CU, whereby only PC (p < 0.05) was significantly different from control. Our results suggest that blood mononuclear cells contribute to extrarenal 1,25(OH)2D3 synthesis in hemodialysis patients, and that this synthetic activity may be related to the hemodialysis procedures. PMID- 1300436 TI - Potential deleterious effect of furosemide in radiocontrast nephropathy. AB - The purpose of the study was to determine the efficacy of furosemide in addition to intravenous fluids in the prevention of radiocontrast nephropathy. 18 patients, referred to a radiocontrast study, considered at risk because of preexisting renal insufficiency, were enrolled in a prospective, randomized, controlled trial, performed at the secondary care center of a 1,100-bed private university hospital. In addition to fluids, the treatment group received furosemide (mean dose 110 mg) intravenously 30 min prior to the injection of contrast material. The control group received fluids (mean 3 liters). Radiological studies were mostly angiographies performed with both ionic and non ionic contrast material, at an average dose of 245 ml. Renal function significantly deteriorated in the group pretreated with furosemide (p < 0.005 by ANOVA), with a rise in serum creatinine from 145 +/- 13 to 182 +/- 16 mumol/l at 24 h, while no change occurred in the control group (from 141 +/- 6 to 142 +/- 7 mumol/l). Renal failure was associated with weight loss in the furosemide-treated group. Furosemide may be deleterious in the prevention of radiocontrast nephropathy. PMID- 1300437 TI - Effect of lymphokine from nephrotic peripheral blood mononuclear cells on catabolism of rat glomerular basement membrane sulfated compounds. AB - We have previously shown a significant increase in sulfate-35 uptake in rat glomerular basement membrane (GBM) when glomeruli were cultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse. In the present study, we have isolated the lymphokine mediating the augmented sulfate-35 incorporation and evaluated its effect on the catabolism of the GBM sulfated compounds. Supernatants from IMLNS PBMC cultures of 13 patients in relapse and 10 in remission were fractionated using gel filtration chromatography. There was a significant increase in rat GBM sulfate-35 uptake when glomeruli were cultured in carbonic anhydrase fraction from patients in relapse (12.9 +/- 3.2; cpm/microgram GBM protein, mean +/- SEM) as compared to glomeruli cultured in the same fraction from patients in remission (8.2 +/- 2.5: cpm/microgram GBM protein; p < 0.05). The catabolism of the GBM sulfated compounds was determined by studying the washout of the sulfate-35 macromolecules after equilibration in sulfated isotope-free medium for 12 h. There was a significant decrease in residual sulfate-35 in rat GBM when glomeruli were cultured in a 29-kD fraction from patients in relapse (7.0 +/- 2.5; cpm/micrograms GBM protein, mean +/- SEM) as compared to glomeruli cultured in the same fraction from patients in remission (31.8 +/- 1.6; p < 0.005). No significant differences in sulfate-35 incorporation were seen when other fractions from patients in relapse and in remission were compared. These studies suggest that the lymphokine secreted by PBMC from IMLNS patients in relapse increases the catabolism of the GBM sulfated compounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300438 TI - Comparison of haemostatic activity in haemodialysis and peritoneal dialysis patients with a novel technique, haemostatometry. AB - Bleeding due to impaired primary haemostasis is common in uraemia. However, thrombo-embolic episodes are also a clinical problem in dialysis patients. Platelet reactivity to shear stress (haemostasis, H1 and H2), exposure to collagen fibre (thrombus growth) and coagulation of flowing blood (clotting time, CT1 and CT2) were measured in non-anticoagulated blood samples taken immediately before and 18-24 h after haemodialysis (n = 26) and from patients maintained on continuous ambulatory peritoneal dialysis (CAPD, n = 30). H1 (p < 0.001), H2 (p < 0.01), percent thrombus growth rate (p < 0.03), CT1 (p < 0.01 and CT2 (p < 0.05) were restored towards normal after haemodialysis. Results obtained in the CAPD patients demonstrated that the mean values for formation of the haemostatic plug lay between the pre- and posthaemodialysis values; however, CT1 (p < 0.01) and CT2 (p < 0.05) were prolonged in CAPD compared with values after haemodialysis. These data, which indicate platelet function from non-anticoagulated blood and coagulation under flow conditions, (1) confirm that there is impaired haemostasis in uraemia; (2) demonstrate an improvement in haemostasis after haemodialysis; (3) show that peritoneal dialysis results in a haemostatic profile which falls between the pre- and posthaemodialysis pattern, and (4) show that neither dialysis modality returns haemostasis to normal. PMID- 1300439 TI - Nephropathy associated with infection by human immunodeficiency virus: a report on 11 cases including 6 treated with zidovudine. AB - The human immunodeficiency virus (HIV) was recently suggested to be involved in generating kidney lesions in HIV-associated nephropathy (HIVN). The possibility that antiretroviral agents can slow down the usually explosive evolution of HIVN to end-stage renal failure (ESRF) has not been studied in many of the series of cases published. The present work is a retrospective analysis of 11 patients with histologically proven HIVN, 6 of whom were treated with zidovudine. Seven patients (group 1) either required dialysis at the outset, when HIVN was diagnosed, or progressed very fast to ESRF within 15-45 days. Two patients of this group were treated with zidovudine, but it had no effect on kidney function. In the remaining 4 patients (group 2), HIVN progressed more slowly than in group 1. All 4 patients were treated with zidovudine at an earlier stage of the disease than ESRF. Only 1 deteriorated to ESRF in 9 months. The 3 others, who did not have ESRF, were followed up for 13, 10 and 32 months, respectively. Although this is a preliminary study, its results do suggest that zidovudine can slow down the evolution of HIVN to ESRF. They highlight the need to screen HIV-positive patients regularly for proteinuria, in order to detect HIVN by renal biopsies at an early stage of renal lesion formation. PMID- 1300440 TI - Seroprevalence of antibodies to the human immunodeficiency virus in dialysis workers: results of a multi-center study. AB - The Center for Devices and Radiological Health, in collaboration with the Department of Veterans Affairs Medical Center, Brooklyn, N.Y., conducted a multi center, multi-institutional study of the seroprevalence of antibodies to the human immunodeficiency virus (HIV) among dialysis workers. Seven dialysis units and 112 dialysis workers participated in the study over a period of 2 years. Participation was limited to dialysis workers who, by questionnaire, denied non occupational risk factors for HIV infection. The vast majority of the study participants were drawn from areas where the prevalence of HIV infection and AIDS cases are substantially greater than the national average. Study participants received the ELISA test for HIV antibodies. All 112 of the participants tested negative for HIV antibodies. These results are encouraging, as they failed to reveal unrecognized occupational transmission of HIV infection among dialysis workers. PMID- 1300441 TI - Effect of eicosapentaenoic acid on the progression of chronic renal failure in rats. AB - Eicosapentaenoic acid (EPA) can induce a shift in prostaglandin and leukotriene synthesis. The effects of EPA supplementation of the diet on the progression of chronic renal failure (CRF) were evaluated in a model of 5/6 renal mass ablation in rats. After 30 or 60 days of CRF, elevation in single-nephron glomerular filtration rate due to an increase in glomerular plasma flow and hydraulic pressure was observed. These hemodynamic alterations were followed by a rise in proteinuria and glomerular sclerosis. EPA treatment for 30 or 60 days did not substantially modify the hemodynamic or morphological profiles induced by renal mass ablation. In the present non-immune model of CRF, preglomerular vasodilation with glomerular hyperperfusion and hypertension were responsible, at least in part, for the presence of proteinuria and glomerular sclerosis. No additional vasodilation was observed in the present model of CRF, and, thus, hemodynamic effects induced by EPA did not modify renal damage, in contrast to the EPA effects observed in immune-mediated models of CRF. PMID- 1300442 TI - Enhanced urinary excretion of eicosanoids in fawn-hooded rats. AB - Compared to Wistar (WAG) rats, rats of the fawn-hooded (FH) strain have a high level of glomerular filtration rate (GFR) and urinary protein excretion (UpV). To investigate the possible role of vasoactive eicosanoids in this spontaneous model of hyperfiltration and proteinuria, we compared the urinary excretion of thromboxane-B2 (TxB2), 6-keto-prostaglandin (Pg)F1 alpha and PgE2 in male FH and WAG rats during normal ageing. All measurements were performed sequentially in the same animals 12, 24, 36, 48 and 60 weeks after weaning. Throughout the study, GFR was higher in FH rats as were the filtration fraction and UpV. From week 24, UpV in FH rats increased progressively. No elevations in UpV were observed in WAG rats. At weeks 12 and 24, the urinary excretion of TxB2, 6-keto-PgF1 alpha and PgE2 was 2-4 times higher in FH rats compared to WAG rats. With time, a shift in the urinary excretion from vasodilator to vasoconstrictor eicosanoids was observed, i.e., the excretion of PgE2 declined and that of TxB2 increased. Proteinuria in FH rats was positively correlated with TxB2 excretion and negatively correlated with PgE2 excretion. We conclude that in FH rats, early hyperfiltration coincides with enhanced urinary excretion of all eicosanoids. Subsequent progressive proteinuria is associated with an increase in TxB2 and a decrease in PgE2 excretion. PMID- 1300443 TI - Double monoclonal cryoglobulinemia, glomerulonephritis and lymphoma. AB - We present a case of monoclonal cryoglobulinemia with double monoclonal component IgA lambda-IgG lambda, without complement activation, membranoproliferative glomerulonephritis (MPGN) with deposits of IgA, IgG and lambda chains and lymphocytic IgA-lambda-chain-secreting lymphoma. This case emphasizes the possibility that double monoclonal cryoglobulins could behave differently compared to type I cryoglobulins, determining a MPGN-like type II cryoglobulins do, but without activating the complement cascade. PMID- 1300444 TI - High-dose intravenous gamma-globulin in systemic lupus erythematosus. PMID- 1300445 TI - Is there a relationship between citraturia and kaliuria among stone formers? PMID- 1300446 TI - Plasma endothelin-1 levels in patients with hyponatremia. PMID- 1300447 TI - Increased lipoprotein (a) levels in subjects with chronic renal failure on hemodialysis. PMID- 1300448 TI - Acute renal failure in the intensive care unit. PMID- 1300449 TI - Ibopamine in idiopathic edema. PMID- 1300450 TI - More about renal disease in type Ia glycogen storage disease. PMID- 1300451 TI - Recombinant human erythropoietin treatment may induce antithrombin-III depletion. PMID- 1300452 TI - Polycystic kidney disease associated with polycystic ovarian syndrome. PMID- 1300453 TI - Is measurement of serum antigliadin antibodies in patients with suspected IgA nephropathy worthwhile? PMID- 1300454 TI - [Physical basis of therapeutic uses of lasers]. AB - Therapeutic applications of lasers usually require different mechanisms of laser tissue interaction: the thermal interaction mechanism where light energy is converted into heat, the photochemical interaction mechanism where light induces chemical reactions, the mechanical interaction mechanism where light produces shock wave and the photoablative interaction mechanism where light energy produces desorption of tissue. The interaction mechanism depends on the choice of the laser parameters. PMID- 1300455 TI - [Carbon dioxide laser and stereotaxic craniotomy]. AB - This article describes the development and contemporary clinical applications for a computer interactive volumetric stereotactic system in CT and/or MRI-based resection of superficial and deep seated intracranial lesions. The carbon dioxide laser was found to be particularly useful in the resection of deep seated lesions by this volumetric stereotactic method for three reasons: 1) the CO2 laser is a convenient tool for removing tissue from the depths of a deep cavity, 2) it is relatively hemostatic, and 3) the precision provided by the CO2 laser renders it safer than other methods for dissecting tumors from important brain tissue, e.g. the internal capsule. The specific clinical methods of the technique: data acquisition, computer based surgical planning, and interactive stereotactic open surgery are discussed. The clinical experience in 500 consecutive cases in the resection of various lesions from specific anatomical areas is presented. Total overall morbidity was 7% and mortality 1%. We have found the technique of most benefit in the resection of histologically circumscribed intra-axial lesions. PMID- 1300456 TI - [Laser microsurgery of meningioma. An analysis of a consecutive series of 164 cases treated surgically by using different lasers]. AB - Over a six years period, 224 laser procedures were performed in our clinic, of these 164 (72%) involved meningiomas of various intracranial and spinal locations; 82 (50%) tumors were located in the posterior fossa, 36 (32%) were suprasellar or parasellar meningiomas: a carbon dioxide laser was used in 56 cases, a double wave length YAG laser in 101 cases, and recently a simultaneous Nd YAG and CO2 combolaser in 7 cases. Complete tumor removal was accomplished in 83% of cases and overall mortality was 3%. We think that microscope guided laser techniques represents a significant advancement in the ability to remove deep situated meningiomas that might prove difficult to extirpate by conventional microsurgery. The advantages of these methods include: 1. reduced brain retraction; 2. the ability to operate with smaller and different exposures; 3. a reduced amount of mechanical manipulation by vaporizing in first the dural attachment; 4. improved operative precision and 5. decreased intra operative blood loss. PMID- 1300457 TI - [Statistical comparison of surgical results with or without laser in neurosurgery]. AB - In the literature, no significant statistical studies have been published on the effectiveness of laser compared with traditional procedures in neurosurgery; we have decided to study a series of 198 gliomas and 220 meningiomas operated upon either with a laser or with conventional techniques. We considered the post operative morbidity, the duration and the quality of survival. These data have been clearly influenced by the type of surgery. On the contrary, no significative difference was observed concerning the survival rate of gliomas whatever their grading. In the laser-group, morbidity and quality of life are improved (36 months follow-up); but the mortality rate (3 years) is equal in both groups. Concerning meningiomas, patients of both groups (with and without laser) were clinically improved during the post-operative period. A significative difference appears only for meningiomas located in functional areas and operated with a laser. PMID- 1300458 TI - [YAG laser in neurosurgery]. AB - The authors try to answer to some practical questions concerning Yag Lasers in neurosurgery. The aim of this work is to determine the main data useful for the choice of a YAG-Laser. Are considered: the wavelengths which can be bought on the international market (1.06 microns or 1.32 microns for instance), the peripherics at disposal, the tissular effects due to the different lasers, the surgical applications and indications. The Laser unit which will be chosen should be a compromise between the different advantages and inconveniences of a particular laser, its tissular effects, its price. The multi-wavelengths units appear to be, at the present time, interesting compromises (such as 1.32 + 1.06 microns, CO2 + 1.06 microns). PMID- 1300459 TI - [Combined CO2 and Nd-YAG laser in neurosurgical practice. A 1st experience apropos of 40 intracranial procedures]. AB - The authors present their experience concerning the use of Combolaser (Lasermatic, Finland), in neurosurgery. This laser-unit combines two wavelengths (CO2 and 1.06 Nd-YAG) which are emitted simultaneously and coaxially. During the last 12 months, 40 patients harbouring an intracranial tumor were operated upon with such a combolaser unit: 8 infra-tentorial, 32 supra-tentorial, 17 were meningiomas. The mean output power used during the procedures was 3-5 w for both CO2 and Nd-YAG beams. The authors discuss the advantages and inconveniences of such a laser; and they compare it with the other laser-units they have been using for the last 10 years: CO2-Laser, 1.06 Nd-YAG and 1.32 Nd-YAG laser. The main inconvenience of this unit is linked to the utilization of the articulated arm which conducts the CO2 laser beam. This drawback should be avoided or limited by the use of a fiber microguide, which will conduct both CO2 and Nd-YAG beams simultaneously. The principal contribution of a combined-laser unit is the quality of the haemostasis associated to a very good vaporization and cutting effect. When both wavelengths are synchronized, the combined laser beams penetrate into the nervous parenchyma more deeply than the only CO2 laser beam would with the same parameters. The vaporization effect is identical to that obtained with the isolated CO2 laser; the quality of haemostasis is limited to the effects of the Nd-YAG laser. Another advantage must be emphasized: the possibility of utilizing separately the CO2 laser and the 1.06 Nd-YAG. PMID- 1300460 TI - [Stereotaxic laser interstitial thermotherapy. A new alternative in the therapeutic management of some brain tumors]. AB - Laser Interstitial Thermo Therapy (ITT) is a new procedure which has been performed only a few times in our department as well as in foreign services. The aim of an ITT is to increase the temperature of a tumoral target which has been perfectly determined stereotactically. In the center of the target, i-e at the extremity of the laser fibre, temperature reaches 80 degrees 90 degrees C and creates a coagulation necrosis. At the periphery of the target, temperature must be 41 degrees-43 degrees C so as to create a selective lesion of the pathological tissue due to proteinic and enzymatic denaturation. The authors present their experience based on 8 patients who underwent an ITT between June 1990 and October 1991. A stereotactic determination of the tumor is first performed; then two routes are determined for the laser-fibre (Nd-YAG 1.06 microns, fiber diameter: 400 mu) and for the thermic electrode. The ITT itself is performed a few days later (P = 3-5w, time: 800-1200 seconds). Laser heat effects are monitored with MRI controls (H5, H24, D8 then monthly). The authors insist on the importance of a long follow-up so as to be sure of the complete inocuity of such a treatment. It is the only way to broaden and develop laser-ITT procedures as therapeutic alternatives for certain deep-seated intracerebral tumors. PMID- 1300461 TI - [Use of Nd-YAG laser in intracranial endoscopy. An initial experience in stereotaxy]. AB - The authors report on four cases of intra-ventricular lesions surgically treated by endoscopic laser-therapy in stereotactic conditions. Two colloid cysts of the third ventricle, one arachnoidal cyst responsible for with an intracranial hypertension and an intraventricular meningioma were treated with such a procedure. The laser beam was used as a surgical knife on cystic lesions and to vaporize the meningioma. The laser coupled with an endoscope add to the comfort given by direct visualization the precision of surgical instrument the effects of which are perfectly controllable in areas where surgical traumatism must be avoided as much as possible. PMID- 1300462 TI - [Future of medical lasers]. AB - Whatever the medical field of application of lasers, their future is linked to research and to the realization of systems of automatization which will allow the development of "smart lasers". It will be linked to the improvement of imaging techniques and of medical computers, as well as to the development of new feedback systems; the wavelength and the laser beam dosimetry could then be automatically chosen depending on the aimed tissue and on the biophysical effect desired on the target (coagulation, vaporization, cutting, hyperthermia, photo ablation). Practically, the future of lasers also depends on the elaboration of new peripheric systems and a better conception of new laser equipment. At last, clinical evaluation of such new surgical technologies with well adapted procedures, formation and information through specific teaching courses and seminars will help to the development of all new laser-technologies. PMID- 1300463 TI - [Popliteal entrapment syndrome with distal embolization. Description of a clinical case]. AB - External compression of the popliteal artery is probably still underdiagnosed. Repeated minor trauma to the popliteal artery as it passes through anomalous fibrous bands, due to developmental defects, may lead to stenosis and occlusion, with consequent chronic or acute ischaemic symptoms, usually in young males without cardiovascular risk factors. Distal embolization to the tibial arteries, to the foot arch and digital vessels is common but is not emphasized in the literature. This distal embolization may compromise the results of surgical repair. Early repair of the anomaly fibrous band is advocated even in a still asymptomatic lower limb. One patient with bilateral popliteal artery entrapment, causing unilateral occlusion, with distal embolization, is reported. PMID- 1300464 TI - [Arterial hypertension and macroangiopathic complications in a group of diabetic out-patients]. AB - We have retrospectively studied 814 diabetic outpatients, 407 hypertensives and 407 normotensives. The aim of the study was to investigate on possible associations between macroangiopathic complications (coronary heart disease, peripheral and cerebral arteriopathy) and well recognized risk factors for atherosclerosis. Macroangiopathy was present in 27% of males and 24% of females (p = NS), and in 32% of hypertensives and 18% of normotensives (p < 0.0001). Macroangiopathy associated, in both sexes, with age and duration of diabetes, but did not correlate, instead, with metabolic control, obesity, serum cholesterol and triglycerides. High triglyceride levels were associated strictly with arterial hypertension, in both sexes, but are more elevated in men. Risk factors for atherosclerosis seem not to be simply considered in the same way in diabetic and non diabetic populations. PMID- 1300465 TI - [Arterial hypertension secondary to Conn's disease: an infrequent pathology in nephrology. Report of a clinical case]. AB - In this work we describe a case of Conn's syndrome caused by a suprarenal adenoma in a sixty-one year female. The patient had come to our observation because of severe hypertension and hypokalemia. Primary aldosteronism resulting from the secretion of excessive amounts of aldosterone caused by autonomous hyperfunction of the adrenal cortex usually by a solitary adenoma. In most series of unselected patients, it is found in fewer than 0.5% of hypertensives. In our study we demonstrated the circadian changes of arterial blood pressure but we failed to demonstrate the presence of hypertrophic cardiomyopathy as recently emphasized in the literature. Regardless of its rarity, primary aldosteronism is a fascinating disease, protean in its manifestations, logical in its pathophysiology. PMID- 1300466 TI - [Chronic hepatitis. Histologic and epidemiologic findings. A 4-year retrospective study of a caseload]. AB - We evaluated 108 liver biopsies--performed over a four year period (1986-1990) at the Ospedale degli Infermi di Biella--with histologic signs of chronic hepatitis. Histological and epidemiological aspects are here reported. PMID- 1300467 TI - [The clinical pathologist today: medico-legal aspects]. PMID- 1300468 TI - [Chondro-osteoplastic tracheo-bronchopathy. A clinical case]. PMID- 1300469 TI - [Prevention of hepatitis B infection in the neonatal care section of the Biella Hospital during a 5-year period from 1986 to 1991. Results and conclusions]. AB - The paper reports the passive and/or active prophylaxis against hepatitis B virus infection carried out in the Neonatal Section of Biella Hospital during the 5 year period 1986-1991. All neonates and non-neonatal subjects at risk of vertical and/or horizontal contagion were vaccinated. The aim of this study was to compare the levels of compliance in relation to serum controls during pregnancy, acceptance of vaccination, percentages of seroconversion and collateral effects. In conclusion, the author underlines the good compliance both during screening in pregnancy and in accepting vaccination. The percentages of seroconversion were similar to those reported in the literature, as was the incidence of HBsAg positive pregnant women in the local population. Complications were virtually nil both in relation to incidence and severity. PMID- 1300470 TI - [Intrauterine torsion of the spermatic cord]. AB - Description of a clinical case diagnosed in the first hours of life in apparently well newborn. Diagnostic suspicion by palpation and transillumination. Absence of any subjective sign. Inspective symptom the light scrotal swelling. The neonate received an immediate surgical exploration with subsequent orchiectomy. PMID- 1300471 TI - [Meniscal suture through the arthroscopic route. 3 years' experience]. AB - Meniscal suture using an arthroscopic route is a safe method with an extremely low percentage of failure and complications. The two techniques most commonly used (from inside to outside and from outside to inside) are similar. The introduction of the needle as far as possible from neurovascular structures makes the outside-inside technique less risky. In the event of associated rupture of LCA ligament reconstruction must always be performed as well as the repair of the meniscus. Isokinetic evaluation has confirmed the rapidity of functional recovery times. PMID- 1300472 TI - [Microdiscectomy in the treatment of lumbar slipped disk]. AB - The paper describes the surgical technique of microdiscectomy used in lumbar slipped disk and its clinical indications. A total of 113 patients were treated with microdiscectomy over a period of 4 years with positive results in 90% of cases. PMID- 1300473 TI - [Percutaneous needle aspiration in the treatment of contained lumbar herniated disk]. AB - The authors describe the technique of percutaneous fine needle aspiration in contained lumbar slipped disk and its clinical indications. The paper reports a series of 20 patients treated two years with positive results in 75% of cases. PMID- 1300474 TI - [The Brooks-Graner technique in the correction of inveterate mallet finger in sportsmen]. PMID- 1300475 TI - [Microsurgical treatment of carpal tunnel syndrome]. AB - The paper examines a microsurgical technique of neurolysis and epineurotomy in the treatment of the carpal tunnel syndrome. The cases reported comprise an homogeneous group of 61 "idiopathic" syndromes (slight chronic tenovaginitis of the flexors) at the irritative or sensitive stage. A complete recovery was obtained in 70% of cases and patient assessment was good is 90% of cases. From the authors' point of view, the most interesting findings was the complete absence of problems relating to the palm of the hand following renewed activity. PMID- 1300476 TI - [Mitochondrial disease and complete heart block. Kearns-Sayre syndrome. Description of a case]. AB - Defects of the mitochondrial respiratory chain form a clinically and biochemically heterogeneous group of diseases. Mitochondrial diseases include myopathies and multisystem disorders that are defined either by biochemical abnormalities of the mitochondria or by the presence of "ragged red fibers" in muscle-biopsy specimens stained with modified Gomori's trichrome stain. Several syndromes have been identified. Typical Kearns-Sayre syndrome is a sporadic condition that is characterized by an onset before the age of 20, progressive external ophthalmoplegia, pigmentary retinopathy and cardiac disorders. Mitochondrial DNA deletions were found in patient with Kearns-Sayre syndrome. We report the case of a 33 year-old woman, with neuromuscular syndrome of the Kearns Sayre type, insulin-sensitive diabetes and complete heart block, who was implanted a pacemaker. PMID- 1300477 TI - [Primary malignant lymphoma of the heart. Description of a case and review of the literature]. AB - Primary cardiac tumors are rare. Approximately 25% of primary cardiac tumors are malignant, with the majority of these being sarcomas. Primary lymphoma of the heart is a very rare malignancy, usually recognized at autopsy or fatal within a few weeks of diagnosis. we report the case of a patient with diffuse large uncleaved cell lymphoma of the heart who had dyspnea, distention of the neck veins, edema of the face and arms. The diagnosis in this patient was aided by 2D echocardiography, CT scan of the chest and superior vena caval angiography. The diagnosis was confirmed at operation and by histological examination. Surgical procedures were only palliative and aimed at prolonging life. However, prognosis remained severe and unchanged. PMID- 1300478 TI - [Wandering spleen. Considerations on 2 clinical cases]. PMID- 1300479 TI - [Halo-vest in the treatment of fractures of the upper cervical spine. Fractures of the epistropheus]. AB - The authors examine the use of a halo-vest brace in the treatment of fractures of the upper cervical spine. This brace forms a valid alternative to the classic plaster cast in that it is easily positioned, well tolerated by the patient and has a high restrictive capacity for the centre of the fracture. In the cases treated by the authors no complications were reported during treatment, and consolidation time was shortened by 30 days in relation to traditional plaster cast treatment. PMID- 1300480 TI - [Rehabilitative evaluation of 18 cases of anterior cruciate ligament lesions surgically treated by the Kenneth-Jones technique]. PMID- 1300481 TI - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced astrogliosis does not require activation of ornithine decarboxylase. AB - Mechanical injury to the brain results in enhanced immunostaining for glial fibrillary acidic protein (GFAP) that is markedly inhibited by difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. In the current study, systemic exposure of mice to the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), also increased GFAP but, unlike mechanical injury, this increase was not prevented by DFMO pretreatment. These results indicate that de novo polyamine biosynthesis is not obligatory for the MPTP-induced increase in GFAP. MPTP administration, unlike mechanical injury, does not disrupt the blood-brain barrier; thus, a role for polyamine biosynthesis in the astrocyte response to injury may be restricted to insults involving a compromised blood-brain barrier. PMID- 1300482 TI - Selective inhibition of homosynaptic depression in a tetanized pathway by an adenosine A1 blocker in the CA1 region of rat hippocampal slice. AB - The involvement of adenosine A1 receptors in post-tetanic depression (PTD) of CA1, induced by 5 Hz, 20 s stimulation to the Schaffer collateral/commissural fibers was studied in the rat hippocampal slice. The tetanic stimulation induced post-tetanic depression (PTD) lasting for 5-10 min in the excitatory postsynaptic potentials (EPSP) and the population spike (PS) of the tetanized pathway (homosynaptic PTD), and of a non-tetanized pathway (heterosynaptic PTD). 8 Cyclopentyltheophylline (an adenosine A1 antagonist) blocked the induction of homosynaptic PTD, but not of heterosynaptic PTD. These results indicate that adenosine released during tetanic stimulation acts on the A1 receptor to induce the homosynaptic PTD. PMID- 1300483 TI - Microglia in the mature and developing quail brain as revealed by a monoclonal antibody recognizing hemopoietic cells. AB - The monoclonal antibody QH1, which recognizes quail endothelial and hemopoietic cells, was found to label microglia in the developing and mature brain of the quail. Forms of microglia similar to those described in mammals were labelled. Ameboid microglia predominated at embryonic stages, became less numerous in late embryonic development, and disappeared completely by day 10 post-hatch (P10). Poorly ramified microglia were present as early as day 5 of incubation (E5), and were progressively replaced by mature ramified microglia from E14 onwards. From P10 onwards, ramified microglia were the only microglial form seen in the quail brain. PMID- 1300484 TI - Distribution of NADPH-diaphorase positive somata in the brainstem of the monitor lizard Varanus exanthematicus. AB - The distribution and size of presumptive cholinergic somata in the brainstem of the Savanna monitor lizard Varanus exanthematicus were determined using the enzyme histochemical marker NADPH-diaphorase. Numerous neurons were labelled in the lizard brainstem with this technique. A three dimensional computer reconstruction of this population revealed that it shows marked similarity to the laterodorsal tegmental/pedunculopontine tegmental cholinergic cell column, an NADPH-diaphorase positive population in the mesopontine tegmentum of the mammalian brainstem. PMID- 1300485 TI - Immunohistochemical evidence for a crossed cholecystokinin corticostriatal pathway in the rat. AB - Using the indirect immunofluorescence technique, the effects of decortication and callosotomy on the pattern of cholecystokinin (CCK)-like immunoreactivity were studied in the striatum of the rat. Decortication plus callosotomy, but not decortication alone, caused a strong decrease in the immunoreactivity on the side ipsilateral to the lesion. An almost complete disappearance of CCK immunoreactive patches in the medial-dorsal aspects of the striatum was observed. These results indicate that part of the striatal CCK immunoreactive fibres are of cortical origin, to a considerable extent from the contralateral side. PMID- 1300486 TI - Recombinant human tumor necrosis factor alpha constricts pial arterioles and increases blood-brain barrier permeability in newborn piglets. AB - Tumor necrosis factor alpha (TNF alpha) plays a significant role in the pathogenesis of central nervous system infections. We investigated the effect of intracisternal injection of recombinant human TNF alpha (50-50,000 IU) on pial vasoreactivity and blood-brain barrier permeability in newborn piglets. The cytokine administration resulted in arterial vasoconstrictions, blood-brain barrier opening for Na-fluorescein (mol. wt. 376 Da) and increased Na-fluorescein uptake in brain regions examined (parietal and occipital cortex, cerebellum, pons/medulla, periventricular white matter) in a dose-dependent manner. TNF alpha may be involved in the pathophysiology of neonatal brain injuries. PMID- 1300487 TI - Developmental changes in the hypoxia tolerance of the in vitro respiratory network of rats. AB - The functional relation between respiratory activity, extracellular potassium activity (aKe) and tissue oxygen pressure (pO2) was analyzed in vitro in the ventral respiratory group (VRG) of the neonatal brainstem-spinal cord (NB) and the perfused adult brainstem (AB) of rats. In the AB, an aKe increase of up to 35 mM and a reversible blockade of respiratory activity occurred during anoxia periods of 5-10 min. In the NB, respiratory activity persisted during a 60 min anoxia in CO2/HCO3(-)-buffered solutions and aKe increased by less than 1.5 mM. In both preparations, inhibition of glycolysis by iodoacetate led to an irreversible blockade of respiratory rhythm and a delayed increase of aKe by more than 15 mM. We conclude that anaerobic metabolism is sufficient for the maintenance of respiratory activity and potassium homeostasis in the brainstem of the neonatal rat, but not of the adult. PMID- 1300488 TI - Adenosine A2 receptor antagonist facilitates the reversal of long-term potentiation (depotentiation) of evoked postsynaptic potentials but inhibits that of population spikes in hippocampal CA1 neurons. AB - The effects of the adenosine A2 receptor antagonist CP-66713 on the reversal of long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of LTP (depotentiation, DP) was effected by delivering a train of low-frequency afferent stimuli (depotentiation stimulation, DPS) which was given 20 min after tetanus (100 Hz, 100 pulses). DPS (1 Hz, 1000 pulses) was applied during perfusion of CP-66713 (10 microM). In the presence of CP-66713, DPS reduced the potentiated component of the slope of the field EPSP (S EPSP) and the amplitude of the population spike (A-PS) by 101.7% and 19.1% of the potentiated amount, respectively (mean, n = 8). The reduction of LTP of the S EPSP was significantly larger than the control (68.5% (mean, n = 6)) while that of the A-PS was significantly smaller than the control (80.1% (mean, n = 6)). Based on these results, we conclude that the inhibition of DP in the EPSP, the facilitation of DP in the PS, and the consequent attenuation in the EPSP-PS relationship follow from activation of adenosine A2 receptors. PMID- 1300490 TI - Multiple projection of vagal non-myelinated afferents to the anterior insular cortex in rats. AB - Projection of the vagal C-afferent to the insular cortex was examined in rats. Electrical activation of the C-afferent resulted in two cortical field potentials in the anterior insula. They were independent of each other and neither of them was attributed to the specific thalamic projection. These results imply that vagal information is conveyed to the cerebral cortex by more than one pathways. PMID- 1300489 TI - Evidence for G protein modulation of experimental-generalized absence seizures in rat. AB - Pertussis toxin is known to inhibit G proteins via ADP-ribosylation, and a response to pertussis toxin is presumptive evidence of G protein modulation of the activity being studied. Therefore, in order to test the hypothesis that G protein-mediated mechanisms are involved in the pathogenesis of generalized absence seizures, the effect of pertussis toxin in two pharmacological models of generalized absence seizures in rat was investigated. The experimental absence seizure models used were the gamma-hydroxybutyrate (GHB) model and low dose pentylenetetrazole (PTZ) model in rat. Pretreatment with pertussis toxin administered intracerebroventricularly (i.c.v.) resulted in a significant decrease in duration of seizure in both models. These data suggest that G-protein mediated mechanisms may be involved in the pathogenesis of the bilaterally synchronous spike wave discharges (SWD) that characterize experimental absence seizures. PMID- 1300491 TI - Tonic suppression of baroreceptor reflex response by endogenous neuropeptide Y at the nucleus tractus solitarius of the rat. AB - We evaluated the potential participation of endogenous brain neuropeptide Y (NPY) in central cardiovascular regulation, using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Bilateral microinjection of NPY (4.65 pmol) into the caudal one-third level of the nucleus tractus solitarius (NTS), the terminal site for baroreceptor afferent fibers, promoted a significant suppression of the baroreceptor reflex (BRR) response. The maximal inhibition occurred at 30-40 min postinjection, and amounted to -42.7 +/- 8.6% (mean +/- S.E.M., n = 9). The same treatment, however, only caused transient (approximately 5 min) hypotension and bradycardia. Blocking the endogenous NPY activity at the NTS with its antiserum appreciably enhanced the sensitivity of BRR response (+ 59.2 +/- 18.8%, mean +/- S.E.M., n = 6), but had no appreciable effect on systemic arterial pressure or heart rate. These results suggest that neurons that contain NPY may participate in central cardiovascular regulation by tonically suppressing the BRR response, possibly by exerting an influence on the baroreceptive neurons at the NTS. PMID- 1300492 TI - Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons. AB - In the infant and adult human basal ganglia, the finding of mRNA exclusively in the striatal medium-sized neurons together with the detection of [3H]CP55,940 binding sites in the caudate-putamen, accumbens, substantia nigra pars reticulata and globus pallidus suggests cannabinoid receptor localization on the striatal intrinsic enkephalinergic and substance P-projecting neurons and on their nigral and pallidal terminals. However, the consistent finding of higher binding in the substantia nigra pars reticulata and medial part of the globus pallidus over its lateral segment suggests cannabinoid receptor enrichment on the striatal substance P neurons which express selectively the dopamine D1 receptor. PMID- 1300493 TI - Effects of reducing plantar support on anticipatory postural and intentional activities associated with flexion of the lower limb. AB - This study examines the anticipatory dynamics of the center of gravity and the EMG activity of ipsi- and contralateral (to the moving leg) soleus (SOL) and tibialis anterior (TA) in flexion of the lower limb executed from different plantar support surfaces. Subjects were standing initially on a plane surface or a surface reduced to two narrow rods under the moving or stance foot. Reduction of the plantar support surface under the moving limb induced a decrease in the anticipatory activity of both TA and in the intentional ipsilateral SOL EMG activity, but the anticipatory activity of SOL did not change. The lateral and vertical accelerations of the center of gravity decreased. When the reduction was under the stance limb, the biomechanical traces did not change markedly and the EMG activity was similar to that of the control situation. The differential effects in EMG activity, depending on whether the reduced plantar surface was under the moving or the stance side, suggest that tonic plantar stimulation induces complex reflex actions on muscles involved in the preparation and execution of voluntary movement. The functional demand could explain the gating from one motor organization to another. PMID- 1300494 TI - Stimulation of the hamster ventral lateral geniculate nucleus induces Fos-like immunoreactivity in suprachiasmatic nucleus cells. AB - The suprachiasmatic nucleus (SCN) functions as a pacemaker for circadian rhythms in rodents. Its activity and, therefore, circadian rhythms, are synchronized by light information from both a direct retinal projection and an indirect projection from the thalamic intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (vLGN) (geniculohypothalamic tract; GHT). The GHT also appears to be important for synchronizing circadian rhythms to non-photic cues. Light can activate expression of several immediate-early genes in the SCN, including c-fos. We examined whether electrical stimulation of the IGL/vLGN region would induce Fos-like immunoreactivity (lir) in the hamster SCN. Electrical stimulation was given for one hour during the dark period of the lighting cycle. Stimulation at night of the IGL and adjacent LGN regions induced Fos-lir in cells in the SCN. Labeled cells were found in the dorsolateral part of the caudal SCN, and not in rostral or central regions of the SCN, nor in the ventral part of the caudal SCN. These results indicate that activation of cells contributing to the hamster GHT can induce Fos-lir in a restricted region of the caudal SCN. PMID- 1300496 TI - A high concentration of NPY (Y1)-receptor mRNA-expressing cells in the rat arcuate nucleus. AB - The Y1 neuropeptide Y (NPY) receptor cDNA was recently cloned from a rat brain library. In situ hybridization histochemistry using a synthetic oligonucleotide probe complimentary to bases 716-764 of the Y1 receptor cDNA was used to localize the corresponding mRNA in the rat brain with special reference to the hypothalamic arcuate-paraventricular axis, because these areas are considered to play a key role in eating behavior. Quantification of the hybridization signals by a computerized image analyzing system revealed that the arcuate nucleus together with the granular cell layer in the gyrus dentatus contained a high concentration of Y1 mRNA. In emulsion-dipped sections, the neurons containing Y1 mRNA transcripts were found particularly in the ventromedial part of the arcuate nucleus. These data indicate that NPY or NPY-related peptides via a Y1 receptor on neurons of the arcuate nucleus may influence the homeostasis. PMID- 1300495 TI - Responses of neurons in the rat anterior hypothalamic periventricular zone to osmotic stimulation and angiotensin II in vitro. AB - Extracellular recordings were made in vitro from neurons in slices of the rat periventricular zone surrounding the anterior portion of the third ventricle. Spontaneous unit activity of these neurons was decreased in 39.5% of the neurons tested, increased in 32.9%, and biphasically changed (i.e., excitation inhibition) in 10.5%, in response to bath application of hypertonic artificial cerebrospinal fluid (aCSF) containing elevated levels of NaCl (330 mOsm). Similar responses were observed following bath application of hypertonic aCSF prepared with additional mannitol. Angiotensin II in the perfusion medium dramatically increased spontaneous unit activity in 73.7% of neurons tested, while, unexpectedly, 5.3% were inhibited. These results suggest that some neurons in the periventricular zone are themselves osmosensitive, and may be involved in the regulation of water balance. PMID- 1300497 TI - Phorbol esters and K+ up-regulate alpha-bungarotoxin binding sites in cultured chromaffin cells through a related mechanism. AB - Nicotinic alpha-bungarotoxin (alpha-BGT) receptors in cultured chromaffin cells are up-regulated in response to long term (days) exposure to nicotinic antagonists, elevated K+, and activators of protein kinase C (PKC), such as the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA). The present experiments were done to determine whether their was any interaction in the ability of PMA and K+ to up-regulate the alpha-BGT receptors. Chromaffin cells were treated for 3 days with both 100 nM PMA and 20 mM K+, concentrations which produce maximal responses on their own. The increase in alpha-BGT binding after the combined treatment was the same as that seen with K+ alone suggesting that K+ inhibited the PMA-mediated effect. The K(+)-induced increase in toxin binding was partially prevented by polymyxin B, an agent which completely inhibited the PMA induced increase. The time courses of the increases in binding induced by both K+ and PMA were similar in that the most marked increases in binding were observed at the later time points. The PMA-induced up-regulation was partially inhibited by an activator of adenylate cyclase, a result similar to that previously seen with K+. The present studies suggest that the up-regulation of alpha-BGT receptors induced by K+ shares similarities with that induced by phorbol esters. The observations that K+ inhibited the PMA induced increase and that a PKC inhibitor partially blocked the K+ response suggest that the K+ and PMA mediated induction of the alpha-BGT sites may be linked with the effects of K+ preceding those of PMA. PMID- 1300498 TI - Distribution of amyloid in the brainstem of patients with Alzheimer disease. AB - A4 protein (beta-protein, beta-amyloid) deposits were identified with silver stains in postmortem brainstem sections from 13 patients with Alzheimer disease (AD), 6 patients with mixed Alzheimer disease and Parkinson disease (AD-PD), 5 disease controls, and 2 elderly controls. A rostro-caudal gradient of A4 was found in patients with AD and AD-PD, such that A4 was most prevalent in the midbrain and least prevalent in the medulla. The brainstem of the controls contained little or no A4. The midbrain tectum and tegmentum contained the greatest densities of A4, but the red nucleus and substantia nigra pars reticulata were largely spared. This distribution of A4 suggests that A4 deposition is a function of synaptic connectivity rather than passive diffusion from vascular sources. PMID- 1300499 TI - Age-dependent effects of lead on [3H]MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies. AB - Lead (Pb2+) is a more potent inhibitor of [3H]MK-801 binding to rat neuronal membranes than Zn2+ and Mg2+. The inhibitory effects of Pb2+ appeared to be age dependent since the IC50 was significantly lower in cortical membranes prepared from neonatal than from adult rats. The results also indicate that the hippocampus is more sensitive than the cerebral cortex since the Pb2+ IC50 was significantly lower in the hippocampus. These findings suggest developmental and regional brain heterogeneity to the inhibitory action of lead on [3H]MK-801 binding. Chronic in vivo exposure to Pb2+ resulted in the loss of [3H]MK-801 binding sites in the cerebral cortex of neonatal but not of adult rats. These lead-induced changes may influence developmental processes requiring NMDA receptor activation. PMID- 1300500 TI - Neuroprotective effects of carvedilol, a new antihypertensive, at the N-methyl-D aspartate receptor. AB - Carvedilol's potent antioxidant activity could explain its protective action in brain ischemia, but may not apply to glutamate-induced excitotoxicity in cultured cerebellar granule cells, since glutamate neurotoxicity was not associated with the formation of lipid peroxidative products. Rather, carvedilol diminished the N methyl-D-aspartate (NMDA)/glycine-induced increase in intracellular calcium ([Ca2+]i), lowering [Ca2+]i by a maximum of 66 +/- 5% (n = 8) with a 50% inhibitory concentration of 0.8 microM. Prior addition of 5 microM dihydropyridines did not shift the dose-response of carvedilol, but did significantly lower the NMDA/glycine-stimulated response to 64% of untreated (n = 8, P = 0.014). Inclusion of 5 microM carvedilol before the additions of NMDA/glycine prevented 85% of the increase in [Ca2+]i. Furthermore, carvedilol displaced 3[H]MK-801 binding to rat brain cortical membranes with a Kd of 29.4 +/ 2.2 microM (n = 6) and no selectively for the glutamate or glycine binding sites. These data therefore suggest that, in addition to its antihypertensive and anti-lipid peroxidative functions, carvedilol has neuroprotective activity as a calcium channel blocker and as a non-competitive inhibitor at the NMDA receptor. PMID- 1300501 TI - Co-release of neuropeptide Y (NPY) and noradrenaline from the sympathetic nerve terminals supplying the rat vas deferens; influence of calcium and the stimulation intensity. AB - Epididymal (E) and prostatic (P) segments of the rat vas deferens were incubated with tritium-labeled noradrenaline (NA); upon transmural electrical stimulation for 20 or 60 s (70 V, 1 ms, 3-35 Hz), the outflow of immunoreactive neuropeptide Y (ir-NPY) and NA was detected in the superfusion media. Ir-NPY was detected only following trains of 35 Hz for 60 s in both E and P. In contrast, tritium was released in a graded fashion following trains of 3, 15 or 35 Hz stimulation for 60 s in E, whereas in P it reached a plateau at frequencies larger than 15 Hz. The outflow of tritium, under present conditions, was dependent on the duration of the stimuli, while the release of ir-NPY was only evoked with stimuli of 60 s duration. In the absence of external Ca2+, neurotransmission was blocked and co release of ir-NPY and NA was prevented. PMID- 1300502 TI - Resetting from low threshold afferents of N-methyl-D-aspartate-induced locomotor rhythm in the isolated spinal cord-hindlimb preparation from newborn rats. AB - In this study we have investigated the effects of low threshold afferent stimulation on the centrally generated locomotor rhythm in an isolated spinal cord-hindlimb preparation from newborn (0-3 days old) rats. Locomotor activity was induced by bath application of N-methyl-D-aspartate (NMDA). Stimulation of low threshold afferents (below 2 times threshold (x T) for the incoming volley) in L2 and L3, but not L4 and L5 dorsal roots resets the ongoing rhythm. This is due to an abrupt excitation of the L2 and L3 ventral root bursts and an inhibition of the L5 ventral root burst on the ipsilateral side followed by reciprocal effects on the contralateral side. Similar effects were seen after stimulation of the quadriceps nerve with weak intensity (below 1.8 x T). We conclude that low threshold muscle afferents, possible group I afferents, have access to central pattern generators early in postnatal life and suggest that these findings may give an important opening in ontogenetic studies of how neural networks are assembled. PMID- 1300503 TI - Hippocampal kindling increases the expression of glutamate receptor-A Flip and -B Flip mRNA in dentate granule cells. AB - The level of the mRNAs encoding the AMPA-selective glutamate receptors-A and -B, alternatively splice variants, Flip and Flop, was studied by in situ hybridization in the brains of rats kindled by Schaffer collateral/commissural fiber stimulation. In comparison to control animals, the expression level of the Flip variant of both GluR-A and GluR-B mRNAs was bilaterally enhanced in the dentate granule neurons of kindled animals 24 h after last-generalized seizure, whereas no obvious alterations were observed in the GluR-A Flop and GluR-B Flop mRNA variants. In kindled animals, studied 1 month after the last seizure, GluR-A Flip and GluR-B Flip mRNA had returned to control levels. We suggest that these changes may result in an enhanced glutamate receptor sensitivity in the fascia dentata during kindling. PMID- 1300504 TI - Differential increases of neurokinin B- and enkephalin-like immunoreactivities and their mRNAs after chronic haloperidol treatment in the rat. AB - Changes in neurokinin B-like immunoreactivity (NKB-IR) and neurokinin B mRNA were investigated after daily injection of haloperidol for 10 days on adjacent sections by means of immunocytochemistry and in situ hybridization in the caudate putamen of the rat. In the dorsal striatum the number of NKB immunoreactive perikarya and the staining intensity of striatal efferents increased. The number of NKB mRNA-expressing cells (45%) and the grain density over single positive cells (37%) were significantly higher after the neuroleptic treatment. The levels for enkephalin mRNA were uniformly increased throughout the rostrocaudal extent of the caudate putamen (85%). A main difference to the enkephalin system was that the dorsal pallidum was nearly devoid of NKB-IR in untreated as well as in haloperidol-treated animals. The present data for the first time provide evidence for the regulation of the biosynthesis of NKB after pharmacological intervention. PMID- 1300505 TI - Perisomatic sprouts immunoreactive for nerve growth factor receptor and neurofibrillary degeneration affect different neuronal populations in the basal nucleus in patients with Alzheimer's disease. AB - Aberrant morphological profiles, most likely reflecting a process of perisomatic sprouting, have been detected in Alzheimer's disease (AD) on neurons of the basal nucleus of Meynert by means of Golgi impregnation. Using the mouse monoclonal antibody, ME 20.4., perisomatic profiles were shown to be immunoreactive for nerve growth factor receptor (NGFR). Double label studies using either thioflavin S or anti-neurofibrillary tangle (NFT) antibody B5 in combination with ME 20.4 demonstrated that neurons with aberrant growth profiles failed to express neurofibrillary tangle-bearing material, which otherwise could be detected in large amounts throughout the basal forebrain. The results indicate that in AD, neurons in the basal forebrain, not affected by neurofibrillary degeneration, respond to an increased trophic influence. Dendritic sprouting in AD might, therefore, more likely be regarded as an attempt by the nervous system to repair itself following damage rather than as an abnormal process with primary pathologic significance leading to cellular degeneration. PMID- 1300506 TI - Distribution of c-fos expression in brainstem neurons associated with conditioning and pseudo-conditioning of the rabbit nictitating membrane reflex. AB - Experiments were performed to test the hypothesis that there is a characteristic distribution of neuronal c-fos expression associated with the classical conditioning of the rabbit nictitating membrane reflex (NMR). Rabbits were divided into two groups: a conditioning group that received paired tone and airpuff stimuli in a traditional delay NMR conditioning paradigm and a pseudo conditioning group in which the same number of tone and airpuff stimuli were applied but without being paired. Labeling was present in similar brainstem nuclei in both groups of animals. The labeled sites included trigeminal and auditory nuclei in the classical pathway for the nictitating membrane reflex as well as other nuclei such as the raphe nuclei and those in the ventrolateral medulla (VLM). However, there were quantitative differences in the labeling between the two groups. There were significantly more labeled nuclear profiles in the trigeminal nucleus of the pseudoconditioned rabbits, but more labeled nuclear profiles in the raphe nuclei in the conditioned animals. Interestingly, the ratio of the labeling in the raphe versus the VLM strongly differed between the two groups. PMID- 1300507 TI - Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity. AB - To extend the knowledge on the central effects of cytokines, we studied the effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity in rats. After central administration, both tumor necrosis factor alpha and interleukin-1 alpha significantly (P < 0.001) increase the nociceptive thresholds as measured by the hot-plate test. Tumor necrosis factor alpha, but not interleukin-1 alpha decreases spontaneous locomotor activity evaluated by the Animex test. The increase in nociceptive thresholds induced by tumor necrosis factor alpha or interleukin-1 alpha is not affected by the opiate receptor antagonist naloxone, or antisera against the endogenous opioids beta-endorphin, met-enkephalin or dynorphin. The analgesic effect of tumor necrosis factor alpha is completely antagonized by anti-IL-1 antibodies. Moreover, the cyclooxygenase inhibitor indomethacin does not antagonize the increase of nociceptive thresholds induced by either cytokine. PMID- 1300508 TI - Regional and temporal glycerol changes induced by forebrain ischemia in gerbils. AB - Temporal ischemic changes in glycerol and energy metabolites were studied in the striatum, hippocampus and cortex of gerbils subjected to 15 min of bilateral carotid artery occlusion alone or with various periods of recirculation. The same tissue sample served for the determination of glycerol and energy reserve by a simple enzymatic fluoro- and spectrometric assay after perchloric acid extraction. Cerebral ischemia increased the levels of glycerol (8- to 10-fold) and depleted the energy stores. During the first hour of recirculation, the glycerol content decreased and thereafter (at 2 h), normalized in all structures. However, the glycerol content was still twice as high in the striatum and hippocampus as compared to their respective controls. At the same time, an incomplete restoration of energy reserves was observed in these structures. The findings indicate that glycerol is not a stable postischemic indicator of the ischemia-induced membrane damage. PMID- 1300509 TI - In vitro and in vivo effects of ammonia on glucose metabolism in the astrocytes of rat cerebral cortex. AB - Effects of 1 and 5 mM ammonium acetate on glucose metabolism were studied in astrocytes. But for an elevation in the levels of fructose-6-phosphate, phosphoenol pyruvate, and pyruvate, glucose metabolism was unaltered in the presence of 1 mM ammonium acetate. With 5 mM ammonium acetate, but for unaltered lactate, ADP, ATP and decreased aspartate, levels of several intermediates were elevated. Similar results were obtained when astrocytes isolated from hyperammonemic rats were incubated with glucose except for an enhanced production of 14CO2 from [U-14C]glucose. It is suggested that glucose metabolism of astrocytes may not be severely affected in astrocytes of cerebral cortex in acute hyperammonemic states. PMID- 1300510 TI - Circadian rhythms of pineal melatonin release in the pigeon measured by in vivo microdialysis. AB - Circadian rhythms of pineal melatonin release were measured in freely moving pigeons (Columba livia) by in vivo microdialysis. The birds were placed in light dark cycles with 12 h of light and 12 h of darkness (LD 12:12) or continuous dim light (LLdim) after LD 12:12. Although the level of melatonin was various, daily changes of melatonin with higher levels during the dark and lower levels during the light were observed in all of the birds examined. The daily changes of melatonin persisted in LLdim, indicating circadian nature of pineal melatonin release. Moreover pineal melatonin release was inhibited by acute exposure of light during the dark. These results indicate that microdialysis is useful for studying circadian pineal melatonin rhythms of birds. PMID- 1300511 TI - Specific binding of 3N-(2'-[18F]fluoroethyl)benperidol to primate cerebral dopaminergic D2 receptors demonstrated in vivo by PET. AB - 3N-(2'-[18F]Fluoroethyl)benperidol ([18F]FEB) an 18F-labeled analogue of the D2 antagonist benperidol, was evaluated as a tracer for positron emission tomography (PET). PET imaging of a living baboon showed that the fluorinated ligand rapidly localized in vivo within D2 receptor-rich brain tissue, with selective retention lasting over 2 h after tracer injection. Pretreatment of the animal with unlabeled D2-specific antagonist eticlopride (4 mg/kg, i.v.) 1 h before [18F]FEB completely abolished the selective disposition of the radioligand, whereas the regional cerebral blood flow, blood volume and peripheral metabolism/protein binding of [18F]FEB were not changed. Tracer localization when the baboon was pretreated with unlabeled ketanserin (0.55 mg/kg, i.v.) or SCH 23390 (1.1 mg/kg, i.v.) was identical to that for the control case, indicating that the [18F]FEB did not bind to S2 of D1 receptors in vivo. [18F]FEB has advantages compared to previously used PET tracers, and may be an excellent radioligand for non-invasive study of D2 receptor binding. PMID- 1300512 TI - Dynamic visual acuity and contrast sensitivity for static and flickered gratings in a college sample. AB - For a sample of college observers, visual performance was assessed with three types of measures: (1) contrast sensitivity for a range of spatial frequency gratings with 4-Hz flicker, (2) contrast sensitivity for a range of stationary wallchart gratings, and (3) dynamic visual acuity (DVA) for a range of target velocities. Within each of these three performance measures, mean results were generally consistent with previous reports. However, across-test comparisons revealed little commonality of processes between either of the contrast sensitivity scores and the dynamic acuity scores. These findings are discussed in terms of the separate contributions to overall visual performance made by the increasingly popular contrast sensitivity function (CSF) and DVA. PMID- 1300513 TI - Prevalence of disabled stereopsis in a class of optometry students. AB - Stereopsis is said to be disabled when the third dimension (3-D) cannot be perceived during everyday life but can be when viewing conditions are appropriately arranged. To discover a test suitable for detecting disabled stereopsis, I measured stereoacuity, stereolatency, and the subjective difference in depth perception between monocular and binocular vision of a group of 41 optometry students. Only 2 students showed no sign of this disability. A predictive value for each test was calculated from the results of 14 students whose disability was confirmed by another means. Stereoacuity had the worst predictive value (43%) and stereolatency the best (100%). The prevalence of disabled stereopsis in this group was no less than 34% and might have been as great as 95%. PMID- 1300514 TI - Stereolatency: a stereopsis test for everyday depth perception. AB - An instrument is described which tests for the use of stereopsis by measuring how long it takes for depth perception to begin (its latency) after a transition from monocular to binocular vision. Starting at 1 s, the duration of binocular vision is reduced progressively toward a limit of 16 ms (or increased to a limit of 4 s) until the latency of stereopsis is found. The preliminary period of monocular vision acts as a probe for suppression of either eye and allows time for accommodation and vergence to stabilize before binocular vision begins. Typical results are presented. PMID- 1300515 TI - Influence of polarographic cathode diameter on measured oxygen transmissibility of hydrogel contact lenses with optical power. AB - The oxygen transmissibility of a contact lens is defined as its oxygen permeability (Dk) divided by its thickness (L). Transmissibility can be obtained from separate measurements of Dk and L, or from a single measurement of oxygen flux through the lens (as for example by the polarographic method). Dk/L of hydrogel contact lenses with optical power measured by the polarographic method was compared with Dk/L calculated from separate measurements of Dk and L. Polarographic sensors of different cathode diameters were used to show the effect of the area over which the flux is measured on the observed Dk/L. Dk/L from oxygen flux measured by the polarographic sensor was found to be a function of the optical power of the lens and cathode diameter. Dk/L calculated from separately determined Dk and L for optically powered lenses was found to be a function of Dk and the choice of L (central or average). PMID- 1300516 TI - Computerized Moire analysis of progressive addition lenses. AB - A computerized image capture and analysis system capable of 256-level intensity resolution was used to digitize and store images as a 512 by 512 pixel array. The system was used to record a standard square-wave grating (0.80 lines/mm) located 1 m from the camera. Subsequently, an ophthalmic lens was interposed between the camera and the grating. Nonzero lens powers induced magnification and thus altered the spatial frequency of the grating image. Subtractive-type Moire analysis was performed to compare the intensity distributions of the magnified and the unmagnified (reference) gratings. The Moire patterns created using digital, pixel-by-pixel subtraction of the two images showed graphically the power distributions of the lenses studied. These patterns varied noticeably between different brands of progressive-addition lenses (PAL's) of the same nominal power. Using only commercially available components, this method of analysis was both fast and repeatable, and may be of value to manufacturers and large-volume finishers of progressive-addition lenses. PMID- 1300517 TI - Twelve-month success rates with a hydrogel diffractive bifocal contact lens. AB - In this study we assessed success rates over 12 months with a hydrogel diffractive bifocal contact lens. A total of 108 presbyopes were fitted with lenses, and after 12 months 46% were still wearing the lenses. Subjects with previous presbyopic lens-wearing experience achieved greater success (58% of those fitted) than neophyte lens wearers (33% of those fitted, and 17% of all neophyte presbyopes initially expressing an interest in contact lenses before screening). More neophytes failed for nonvision-related reasons than experienced subjects (31% vs. 12% of those fitted). Consequently, when nonvision-related failures were excluded from the calculation of success rates, 59% of those fitted with lenses (49% of neophytes and 66% of experienced subjects) were still wearing the lenses at 12 months. Most discontinuations from lens wear occurred in the first month of the study, the major reason for discontinuation being poor near vision (blur and/or ghosting; 47% of discontinuations). PMID- 1300518 TI - Quantitative analysis of visual acuity through amber discolored lenses. AB - Discoloration of hydrogel contact lenses is frequently encountered in clinical practice and often precipitates lens replacement. This investigation sought to determine if lens discoloration was associated with a compromise in low or high contrast, high illumination visual acuity. This association would lead to a more scientific rationale for lens replacement. Amber lens discoloration was achieved using human-worn 55% water hydrophilic contact lenses (Methafilcon-A) heated in a 1% potassium sorbate, low pH saline solution. A spectrum of 6 discolored lenses was obtained with a peak absorbance at 320 nm. Fifteen subjects, between the ages of 22 and 38 years, were tested wearing each of the discolored lenses. None of the differences in high or low contrast acuity between our discolored and nondiscolored lenses were found to be statistically significant using a paired t test at the 99% significance level. PMID- 1300519 TI - Effect of rigid gas permeable lens flexure on vision. AB - The flexure of spherical rigid lenses (various materials) and a soft lens was measured using automated over-keratometry on 6 adapted rigid lens wearers (12 eyes) whose corneal toricity ranged from 1.37 to 3.87 D. The results showed: (1) that there was no significant difference in flexure between polymethyl methacrylate (PMMA), silicone acrylate, and the fluorosilicone acrylate lenses (whose Dks ranged from 0 to 115). However, Advent (fluoropolymer) did flex significantly more than the other rigid lenses, and significantly less than the soft lens (Bausch & Lomb U4) and (2) that lens flexure of the rigid lenses did not alter over a 2-h period. We also measured high and low contrast visual acuity (HCVA and LCVA), and the results from subjects wearing Advent and the soft lens were significantly worse than with the other rigid lenses. Finally, the results of this study showed no correlation between rigid lens flexure and permeability and between rigid lens flexure and visual acuity when Advent was excluded from the linear regression analysis. PMID- 1300520 TI - Trajectories of changing refractive status. AB - Refractive status can be represented as a point plotted on a three-dimensional graph. As the refractive status changes a curve is traced out on the graph. Trajectories of changing refractive status are illustrated in a number of representative ideal cases. The three-dimensional graphs are shown by means of stereo-pairs. Trajectories are constructed from clinical data and interpreted with reference to the ideal examples. They show changing refractive status with age, after cataract extraction, and after radial keratotomy. The trajectories may prove to be a useful tool for both clinician and researcher. They show overall trends and allow prediction of future changes. Certain types of trajectories could prove to be characteristic of certain conditions and thus be useful for diagnosis. Trajectories allow monitoring of change after intervention. PMID- 1300521 TI - Relative strength of central and peripheral fusion as a function of stimulus parameters. AB - We investigated the role of various stimulus parameters that influence motor fusion responses for peripheral as compared to central fusional stimuli. Results from the initial experiment indicated that a central stimulus equal in size to a peripheral fusion stimulus dominated the response independent of the amount of retinal eccentricity of the peripheral target. A second experiment indicated that the central stimulus dominated even when the peripheral stimulus was larger. However, when the peripheral stimulus was changed in shape so that it became an annulus surrounding the central stimulus, the peripheral stimulus was always stronger. In another phase of the experiment, we found that the extent to which a peripheral stimulus surrounded the central one determined which controlled the response. We concluded that the surrounding perceptual gestalt produced by the peripheral stimulus was the most significant variable determining the relative strengths of central and peripheral fusion stimuli. Clinical implications are discussed. PMID- 1300522 TI - Tear film bubble formation after decompression. AB - Decompression disorders can occur after a reduction in environmental pressure due to dissolved gases forming bubbles in affected tissues. The objective of this study was to evaluate the use of tear film bubble formation as an indicator of decompression. Eleven subjects were exposed to a simulated dive to 30.48 m (100 ft) (in sea water) for 15 min. There was a significant (p < 0.001) increase in tear film bubble formation post-dive. This noninvasive technique may be of value in both research and clinical environments for monitoring decompression. PMID- 1300523 TI - Variation of congenital nystagmus with viewing distance. AB - Involuntary oscillations of the eyes in persons with congenital nystagmus often dampen in intensity (amplitude x frequency) with near viewing. This study examined how changes in viewing distance affect the duration and position variability of foveation periods (intervals of low eye velocity when the target's image is at or near the fovea), as these parameters generally correlate better with acuity than nystagmus intensity. To do so, the horizontal positions of both eyes were recorded by infrared limbal tracking in 4 subjects with congenital nystagmus and 4 normals during monocular and binocular fixation at 200, 40, and 20 cm. At nearer distances, position variability (the standard deviation of horizontal eye position) increased in normal subjects, as well as during foveation periods in the subjects with nystagmus. Other parameters of the nystagmus varied idiosyncratically with viewing distance. In none of the subjects with nystagmus was visual acuity (measured psychometrically) better at 40 cm than at distance. The results show that characteristics of congenital nystagmus do not necessarily improve and, in some instances worsen, with near viewing. PMID- 1300524 TI - Oral fluorescein angiography and fluoroscopy: determination of plasma fluorescein levels and clinical application. AB - One hundred oral fluorescein angiographic explorations were performed in 85 patients of both sexes, mean age 55.57 years, and range 8 to 77 years. Fluorescein was administered as one 250-mg (15 patients) or 500-mg (70 patients) capsule per 15 kg of body weight. In 15 fasting and 15 postprandial patients administered 500-mg capsules, no significant differences by group were found between fluorescein plasma levels. Fundus fluorescence under slitlamp illumination was poor for patients receiving the lower dosage of fluorescein, whereas at the higher dosage it was visible in all but one patient. The best filters were found to be a Kodak-Wratten 47A for the excitation filter and Kodak Wratten 8 for the barrier filter. With a conventional fundus camera and fluorescein angiography filters, good photographs were achieved in all cases. The integrity of the blood-retina barriers was explored for various chorioretinal pathologies. PMID- 1300525 TI - What kinds of leaders are entering optometry schools? AB - The purpose of this study was to determine the parameters of leadership of students entering one optometry school, assess the relation between personality types and leadership during optometry school, and forecast potential for leadership beyond school. Personality inventories of 269 students entering University of Houston College of Optometry (UHCO) from 1988 through 1990 were analyzed for personality type according to Gough's two-vector system (V1 = extroversion/introversion; V2 = norm-favoring/norm-doubting) which results in four types or life styles: Alpha, Beta, Gamma, and Delta. Although some sex and ethnic differences were found, most (71%) optometry students were Alphas (extroverted/norm-favoring), accepted leaders who strive to maintain and advance consensual values. Alphas achieved well in classroom and clinic and were student leaders. A lesser number (10%), mostly women, were Gammas; extroverted but norm questioning, Gammas can provide creative and progressive leadership. Remaining types were Betas (15%) and Deltas (4%), both introverted types who avoid leadership positions. In sum, traditional and, to a lesser degree, innovative leadership potential appears strong among optometry students; they should serve the profession well. PMID- 1300526 TI - [Malignant breast tumors in the population of the province of Varese from 01/01/76 to 12/31/87]. PMID- 1300527 TI - [Immunohistochemical markers of hormone sensitivity of breast carcinoma]. PMID- 1300529 TI - [Classification of proliferative lesions of the breast: quantitative evaluation of changes in parameters related with genetic instability]. PMID- 1300528 TI - [Clinical and prognostic usefulness of Ki67 determination in breast carcinoma]. AB - We studied the correlation between tumor size, nodal status, menopausal status, nuclear oestrogen receptors, disease free survival and Ki67 (proliferation rate) measured by mean of immunohistochemical analysis with monoclonal antibody. Median value was 10%. From December 1986 to October 1989 we studied 236 consecutive patients (pts). Median follow up was 34 months (range 7-51 months). Median age was 56 years (r. 26-82). We observed: 1) lower levels in smaller tumors; 2) poor correlation with nodes involvement; 3) lower levels when nuclear oestrogen receptors were positive. Preliminary data seem to suggest longer disease free survival when Ki67 is low. PMID- 1300530 TI - [Determination of DNA with flow cytometry in fixed material]. PMID- 1300531 TI - [Automatic system for the determination of nuclear antigens. Its application in carcinoma of the breast]. PMID- 1300532 TI - [Static cytometry: a low-cost alternative]. PMID- 1300533 TI - [Breast carcinoma: the positivity of steroid hormone receptors, morphologically demonstrated with 2 different methods, changes the significance of various conventional prognostic factors]. PMID- 1300534 TI - [Correlation between histologic grading and immunohistochemical prognosticators in breast carcinoma]. PMID- 1300535 TI - [AgNORs as an alternative to Ki67on paraffin-embedded material in breast carcinoma]. PMID- 1300537 TI - Vita's In-Ceram all porcelain single-unit and three-unit bridge system achieves strength, esthetics, and biocompatibility. PMID- 1300536 TI - [Static cytometry in the study of ploidy patterns and cellular kinetics in carcinoma of the breast]. PMID- 1300538 TI - Obra '87 regulations for nursing homes: implications for the dental profession. PMID- 1300539 TI - Don't read this! You won't like it! But it is nevertheless true. PMID- 1300540 TI - Direct thrombin inhibitors. AB - Thrombin not only plays an important role in thrombosis and haemostasis but may also be involved in other pathological situations such as the progression of atherosclerotic plaque formation, inflammatory response and neurodegenerescence. It is therefore important to be able to control the action and/or the generation of this enzyme. With this aim in view, a great number of synthetic or recombinant direct thrombin inhibitors have recently been made. They block either the thrombin catalytic site or an anion-binding exosite which is a recognition site for some of its substrates (fibrinogen, thrombin receptor, thrombomodulin, heparin cofactor II) or act on both sites. Some of these inhibitors have revealed a number of advantages over heparin in experimental animal models of thrombosis and haemorrhagic risk. On-going clinical studies with some candidates will establish their real interest for patients. PMID- 1300541 TI - Immunophenotypic characterisation of human peritoneal and alveolar macrophages and of human blood monocytes differentiated in the presence of either GM-CSF or M CSF or a combination of GM-CSF/M-CSF. AB - In vivo, circulating blood monocytes (Mo) migrate into the various tissues where they undergo terminal maturation into macrophages (M phi) with morphological and sometimes functional properties that are characteristic for the tissue in which they reside. This tissue-specific M phi heterogeneity results from the immediate microenvironment, but may also originate from genetically distinct Mo subpopulations. The in vitro transformation of Mo to M phi is thought to reflect the events of the in vivo maturation and thus is widely used as a model to analyse M phi development. To study the heterogeneity within the mononuclear phagocyte system, we have investigated the phenotypic characterisation of mature tissue M phi, blood Mo and Mo-derived M phi cultured in medium with either GM CSF, M-CSF or a combination of both cytokines. Tissue peritoneal and alveolar M phi showed different antigenic specificities, particularly concerning the transferrin receptor and CD68 and CD14 antigens. M-CSF-derived M phi when compared to the other M o populations also exhibited a significantly increased expression of transferrin receptor and CD68 antigen. In contrast, GM-CSF treated cells which exhibited a better long term survival, showed notably more positivity for CD11b and CD32 antigens. These results show that the phenotypic heterogeneity of the different M phi populations is limited and appears to result from discrepancies in the differentiation and/or activation of the cells. The location of the CD68 antigen, which is generally considered to be an intracellular protein, was investigated at the ultrastructural level and found to be exclusively situated at the outer cell membrane. PMID- 1300542 TI - Macrophage activation syndromes. AB - The clinical and laboratory features of 47 cases of macrophage activation syndrome (MAS) were reviewed in a workshop within the Groupe Francais d'Hematologie cellulaire. There was no predilection for a particular age group, while common symptoms at presentation included fever, hepatic and splenic enlargement and profound depression of blood count. Examination of bone marrow aspirates allowed diagnosis to be established in almost all cases. The most characteristic sign of MAS was the presence of well differentiated macrophages without notable cytologic abnormalities but shown to be actively ingesting haematopoietic elements. Haemophagocytic syndromes generally occur in patients who develop infections in the context of preexisting immunologic abnormalities or neoplasms. In the majority of patients evolution of the disease was regressive, once spontaneously but often after antibiotic, antiparasitic and/or antiviral treatment accompanied or not by corticotherapy and/or chemotherapy. Some regressive phases were followed by more or less long term relapse, especially in the case of associated systemic lupus erythematosus. There exists at present no explanation for the occurrence of MAS, although one may remark its association with other pathologies, in particular congenital or acquired immune deficiencies and haemopathies. Several hypotheses have been proposed to explain the appearance and evolution of the disease and at present two pathways of investigation of MAS seen to merit attention: exploration of macrophages themselves and their secretion products and exploration of lymphocytes and NK cells. The current possibilities for these investigations should lead to a greater understanding of the physiopathology of MAS and it is to be hoped that a better application of appropriate therapy will enable control of its evolution. PMID- 1300543 TI - Erythropoiesis in long term cultures of foetal liver cells is transiently obtained on adult but not on foetal adherent cell layers. AB - We have previously reported long term erythroid differentiation of adult bone marrow cells seeded onto adherent cells derived from adult bone marrow. In this paper, we show that the adherent cells obtained from foetal liver do not support the erythroid differentiation of either adult bone marrow cells or foetal liver cells. Adherent layers derived from bone marrow of adult W/Wv mice supported differentiation of adult bone marrow precursors, but foetal liver progenitors only produced erythrocytes for a few weeks and the foetal origin of these red cells was confirmed by haemoglobin typing. The duration and extent of erythropoiesis was generally inversely proportional to the cell dose. Foetal progenitors were as sensitive to erythropoietin as adult cells, but were optimally stimulated at a lower plateau concentration. These results suggest that inhibitory cells present in foetal liver may block erythropoiesis and their growing importance with age may provide an explanation for the arrest of erythropoiesis in the liver at late developmental stages. PMID- 1300544 TI - Haematopoietic microenvironmental status of the 13-day mouse embryonal liver. AB - The haematopoietic microenvironment which is provided by the stromal cells and extracellular matrix elements has been shown to influence the growth and differentiation of haematopoietic cells. However, most of the information thus far available has been derived from experiments performed using Long Term Bone Marrow Cultures and there is as yet no information regarding the haematopoietic microenvironmental status of the developing liver. Stroma were therefore established using 13-day embryonal liver cells, at a point in time when the liver shows peak haematopoietic activity. These stroma when compared to bone marrow stroma showed differences in histochemical staining. 2M NaCl extracts from 13-day embryonal liver were capable of binding pluripotent stem cells and on SDS-PAGE showed a 14 kDa band of increased intensity. The extracts could also induce erythroid colonies in a semisolid medium. However, 13-day embryonal liver stroma were unable to maintain bone marrow stem cells in culture and overall results would suggest differences between the stromal components of bone marrow and embryonal liver. PMID- 1300545 TI - Transmission groups of French HIV seropositive blood donors (August 1985-December 1990). The French Blood Centers. PMID- 1300546 TI - [Recombinant hirudin and its analogs--new perspectives in antithrombotic treatment]. PMID- 1300547 TI - [Primary prostaglandins PGE2, PGF2, prostacyclin and thromboxane in patients with myocardial infarction]. AB - In 47 patients with acute myocardial infarction and in 17 healthy volunteers blood concentration and urinary excretion of PGE2, PGF2 alpha, 6-keto-PGF1 alpha- hydrolysis product of prostacyclin--and TXB2 were determined using RIA. Myocardial infarction patients were found to have significantly higher blood level and urinary excretion of 6-keto-PGF1 alpha, higher blood level of PGF2 and higher urinary excretion of TXB2 than controls, PGE2 urinary excretion was significantly lower. Increased excretion of 6-keto-PGF1 alpha was observed in patients with ventricular arrhythmias. Excretion of all determined prostaglandins was increased in patients with myocardial infarction complicated by atrioventricular block as compared to the other patients. The results suggest, that increase of prostacyclin synthesis in the acute phase of myocardial infarction may provide protection mechanism against heart muscle damage and improve coronary blood flow. PMID- 1300548 TI - [Effect of lovastatin on platelet function in hypercholesterolemic patients]. AB - 18 patients were studied with primary hypercholesterolemia (type II according to Fredricksen) and fasting cholesterol level during low fat diet above 250 mg/dl. Blood samples were taken: I--before lovastatin administration on diet, II--after 4 weeks administration of 20 mg, III--after 4 weeks of 80 mg and IV--4 weeks after the drug discontinued. The following tests were performed: platelets aggregation induced by ADP and adrenaline, PF3 and PF4, platelet MDA, serum triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol. Before treatment patients showed significant platelets hyperaggregation and MDA concentration comparing to the control group. During the drug administration significant lowering of platelets MDA concentration, was observed small but significant HDL cholesterol level increase which correlated with platelet MDA concentration. Availability of PF3 and release of PF4 did not change during study. PMID- 1300549 TI - [Influence of treating hypothyroidism and hyperthyroidism upon psychical reaction time]. AB - The aim of the study was answering the question whether determination of psychical reaction time may be useful for the monitoring of treatment of hypothyreosis and hyperthyreosis. The correlation of disease symptoms (diagnostic index for hypothyroidism after Murray and for hypothyroidism according to Crooks), concentration of triiodothyronine, thyroxine, index of free thyroxine in blood serum and Achilles tendon reflex--with the simple reaction time (srt) as well as with the choice reaction time (chrt) before and during treatment was investigated in 18 patients with primary hypothyroidism and in 24 with hyperthyroidism caused by Graves-Basedow's disease. Two control groups comprised 84 healthy persons. Either in hypothyroidism or in hyperthyroidism the srt and chrt was significantly prolonged. The substitution therapy in hypothyroidism resulted in a normalization of both parameters. On the other hand, administration of thiamazole, especially in the early period of treatment of hyperthyroidism, further prolonged the srt and chrt. A shortening of the time of each of the two reactions occurred, however, when the restoration of euthyroidism was achieved, which was accompanied by reduction of thiamazole dosage. The obtained data point to the usefulness of srt and chrt determination for the diagnosis and therapy monitoring of functional disturbances of the thyroid gland. PMID- 1300550 TI - [Value of plasma testosterone, carcinoembryonic antigen and CA 19-9 in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis]. AB - Diagnostic value was assessed of serum testosterone concentration and compared with that of serum assay of CEA and CA 19-9 in the differential diagnosis of pancreatic cancer (PC) and chronic pancreatitis (CP). Thirty-six patients with PC were compared with thirty-two CP patients. The sensitivity of CA 19-9 (76.9%) in detecting PC was greater than that of testosterone and CEA (30.6% and 30.8%, respectively). The specificity of testosterone and CA 19-9 were comparable (93.7% and 96.4%, respectively). The combination of tests did not enhance the sensitivity and specificity of each test when used alone. The serum CA 19-9 concentration in PC patients was significantly higher then in patients with colon cancer, gastric cancer and benign gastrointestinal diseases. PMID- 1300551 TI - [Treatment of anemia with erythropoietin (rhuEPO) in patients with chronic kidney failure who are not yet in need of dialysis therapy]. AB - Eleven uraemic predialysis patients have been selected for the treatment of anaemia with rhuEPO. Administration of rhuEPO was followed by a significant increase of the Hct value and haemoglobin concentration as well as an improvement of well being. The main adverse effects of rhuEPO therapy were the following: increase of blood pressure, reduction of the residual renal function and increase of serum potassium and phosphorous concentration. Monitoring of the iron status in uraemic predialysis patients on rhuEPO therapy seems to be mandatory. PMID- 1300552 TI - [Effect of opioid receptor blockade with naloxone on plasma renin activity and aldosterone levels in patients with kidney transplantation]. AB - Function of the renin-angiotensin-aldosterone (RAA) system in kidney transplant patients (KTP) is often abnormal as in patients with chronic renal failure. On the other hand the importance of opioids in the regulation of function of endocrine organs is well established. These facts were the background of studies presented in this paper. They aimed to assess the role of opioid receptors in the regulation of the RAA in KTP. 12 patients with a stabilized renal graft function and on cyclosporin A + prednisone therapy and 15 healthy subjects were examined. In all subjects plasma renin activity (PRA), plasma aldosterone level (Ald) and blood pressure were assessed during a 4 hr bed-rest test. In each subject two tests were performed: the first one without naloxone administration, and the second one--after opioid receptor blockade. In KTP significantly elevated PRA and blood pressure and moderately elevated plasma Ald levels were found as compared with normals. After a 4 hr bed rest without naloxone no significant changes of the above mentioned parameters were noticed both in the patients and the controls. After opioid receptors blockade by naloxone a significant decrease of PRA and plasma Ald was observed in both examined groups. This decrease was significantly more marked in KTP than in controls. In addition only in KTP 4 hrs after naloxone administration a significant increase of systolic and diastolic blood pressure was found. Results obtained in this study suggest, that opioid receptors are involved in the regulation of the activity of the RAA system and of blood pressure more markedly in KTP than in healthy subjects. PMID- 1300553 TI - [Role of endothelin in the pathogenesis of renal and cardiovascular diseases]. PMID- 1300554 TI - [Prognostic value of an early peak CK-MB in plasma of patients treated with streptokinase for acute myocardial infarction]. AB - 111 patients below 70 years old, with the first acute myocardial infarctions, 6 hours since the pain occurred--have been treated with streptokinase i.v. In 102 patients we obtained full curve of CK-MB activity. Early peak of CK-MB activity < 15 hours after onset of symptoms we have observed in 59 patients, and late peak of CK-MB activity > 15 hours in 43 patients. There was not any significant statistics differences between early and late groups in frequency of: early ventricular fibrillation (< 48 hours), complex ventricular arrhythmia (in 21 day), heart failure and in-hospital mortality. 1 patient died in hospital in early group and in late group also died 1 patient. The follow-up period was from 10 to 48 months (av. 26 +/- 13). 100 patients left the hospital and the full informations we have obtained in 97 cases. No one died in that time. In the group with early peak CK-MB activity we observed more often the unstable angina and the new myocardial infarction (21%) than in the group with late peak of CK-MB activity (15%), but these differences were nonsignificant. In conclusion our results don't confirm that the early peak of CK-MB activity is the positive risk factor of unstable angina and the new myocardial infarction. PMID- 1300555 TI - [Prof. Zw. Dr.Hab. N. Med. Waclaw Henryk Markert (1898-1992)]. PMID- 1300556 TI - [A man in the high mountains]. PMID- 1300557 TI - [Influence of long-term hemodialysis treatment on total and free thyroxine serum concentration in patients with chronic renal failure]. AB - Many disturbances in functioning of pituitary-thyroid axis in patients with advanced chronic renal failure are well documented. The present paper aimed to assess the influence of duration of haemodialysis treatment on basal and after stimulating TT4 and fT4 serum concentration in uraemic patients. 17 nondialyzed uraemic patients, 15 dialysed up to 50 months, 11 dialysed for 51-100 months, 11 dialysed for more than 100 months and 14 control subjects were examined. In all subjects TT4 and fT4 levels were assessed before and after TRH administration (400 micrograms/i.v.). RESULTS: 1. The patients, independently if the duration of dialysis therapy, did not show any significant differences in basal TT4 from the normal subjects. 2. Nondialyzed and patients dialysed up to 50 months showed significantly lower basal values of fT4 as compared with the patients dialysed longer and with normal subjects. 3. Areas over basal values of TT4 did not show any significant differences in all examined groups. 4. Areas over basal fT4 values were significantly higher in the patients dialysed over 50 months than in the remaining groups. 5. Positive significant correlations were found between the duration of dialysis therapy and basal fT4 as well as area over basal fT4 values. CONCLUSION: Duration of haemodialysis treatment significantly influences the fT4 serum concentration in chronic renal failure. PMID- 1300558 TI - [Influence of long term hemodialysis treatment on total, free and reverse triiodothyronine serum concentration in patients with chronic renal failure]. AB - Many disturbances is functioning of pituitary-thyroid axis in patients with advanced chronic renal failure are well documented. The present paper aimed to assess the influence of duration of haemodialysis treatment on the basal and after TRH stimulation TT3, fT3 and rT3 serum concentration in uremic patients. 17 nondialyzed uraemic patients, 15 dialysed up to 50 months, 11 dialysed for 51-100 months, 11 dialysed for more than 100 months and 14 control subjects were examined. In all subjects TT3, fT3, and rT3 levels were assessed before and after TRH administration (400 micrograms i.v.). RESULTS: 1. All patients showed significantly lower basal TT3 in comparison with normal subjects. 2. Nondialyzed and dialysed patients up to 50 months showed significantly lower basal values of fT3 as compared with the patients dialysed longer and with normal subjects. 3. The basal rT3 in the patients dialysed over 50 months were significantly higher then in nondialyzed, dialyzed up to 50 months and in the control group. 4. Areas over basal values of TT3 and fT3 were distinctly lower in all patients as compared with control group and significantly higher in patients dialysed from 51 100 months than in patients dialysed up to 50 months. 5. Areas over basal rT3 values did not show any significant differences in all examined groups. 6. Positive significant correlations were found between the duration of dialysis therapy and basal TT3, fT3 and rT3. CONCLUSIONS: Duration of haemodialysis treatment is a important factor influencing serum TT3, fT3 and rT3 concentration. This effect is observed in partial normalisation of: a) basal TT3 and fT3, b) reactivity of TT3 and fT3 after THR administration. PMID- 1300559 TI - [Influence of long term hemodialysis treatment on TSH secretion in patients with chronic renal failure]. AB - In patients with advanced chronic renal failure many disturbances in functioning of pituitary-thyroid axis are well documented. The present paper aimed to assess the influence of duration of haemodialysis treatment on the basal and stimulated TSH secretion. 17 nondialyzed uraemic patients, 15 dialysed up to 50 months, 11 dialysed for 51-100 months, 11 dialysed for more than 100 months and 14 control subjects were examined. In all subjects TSH levels were assessed before and 15, 30, 45, 60 and 120 minutes after TRH administration (400 micrograms i.v.). RESULTS: 1. Nondialyzed and dialysed patients up to 50 months showed significantly lower basal values of TSH as compared with the patients dialysed longer and with normal subjects. 2. Areas over basal values of TSH were distinctly lower in all patients as compared with control group. 3. Negative significant correlation between the duration of dialysis therapy and area over basal TSH values was found. CONCLUSION: Duration of haemodialysis treatment influences markedly secretion of TSH in chronic renal failure. PMID- 1300560 TI - [Prognostic value of selected hemodynamic parameters featuring left ventricular systolic and diastolic function in patients with dilated cardiomyopathy]. AB - The goal of the study was the choice of hemodynamic parameters most useful in prognosing the survival of the patients with dilated cardiomyopathy (DCM). The investigated group comprised 40 patients, who underwent left and right cardiac catheterization with left ventricular (LV) quantitative angiography. The day of catheterization was the starting point of the observation, which was performed by means of follow-up regular examinations and information from questionnaires sent to and returned by the patients or their families. The follow-up spanned from 1 to 120 months (means = 43). The hemodynamic parameters of LV systole, ejection, isovolumic relaxation and filling were assessed. The patients were divided into two subgroups featuring survival of less and more than 3 years, respectively. In these two subgroups the following parameters were compared: LVEADP, T constant of relaxation, LVEDP, LVEDVI,+dp/dt max, EF, LV mass/volume ratio, MCSD (midwall circumferential LV stress in early diastole), -dp/dt min. They were also correlated with survival and analyzed in Cutler-Ederer survival tables. CONCLUSIONS: 1. 32% of patients survived more than 5 years. 2. The prognostically most valuable parameters seem to be: -dp/dt min, LVEADP, LVEDVI, EF, LVEDP, MCSD, +dp/dt max. 3. The prognosing of survival in patients with DCM should be based on a multifactorial analysis because of lack of domination of any single factor. PMID- 1300561 TI - [Evaluation of thrombotic risk in young men after myocardial infarction during a period of clinical stability]. AB - The study was aimed at an evaluation of individualized indications for antithrombotic therapy for secondary prevention in a group of 40 young survivors (aged 30-40 years) of myocardial infarction, presenting a stable phase of coronary disease. The control group consisted of 19 healthy men, of approximately similar age distribution. The determinations concerned the following: in vitro ADP and collagen induced platelet aggregation, plasma fibrinogen concentration, factor VII, VIII and antithrombin III activity, protein C concentration, spontaneous fibrinolytic activity and fibrinolytic activity after venostasis, plasminogen and alpha-2 antiplasmin activity. Moreover, to determine correlations with hemostatic parameters lipids, apolipoproteins, glucose, uric acid plasma concentration as well as percentages of lipoproteins and glycolyzed hemoglobin were also studied. In the study group various hemostasis disturbances were found: an increased platelet aggregation induced by low concentrations of ADP, increased plasma fibrinogen concentration and factor VII activity, decreased protein C concentration and impaired plasma fibrinolytic activity after venostasis. Some correlations between hemostatic and lipids parameters were also observed. Results of the study have suggested necessity for the individualized antithrombotic prevention in young survivors of myocardial infarction with antiplatelet and/or anticoagulant drugs. PMID- 1300562 TI - [The role of erythropoietin in blood pressure regulation in patients with arteritis]. AB - Renal erythropoietin production is dependent on local oxygen content of blood which activates so called "oxygen sensors". Taking into consideration altered local renal blood supply in patients with arterial hypertension in the course of arteritis (HA) and from the other side contribution of the renin-angiotensin system in both pathogenesis of hypertension and regulation of erythropoietin production it seemed plausible to undertake this study. The aim of the study was to determine whether and in what extent patients with HA and healthy subjects differ in EPO secretion and whether EPO serum level is related in this patients to renin response to dietary sodium restriction and upright position of the body. 18 patients with HA and 12 healthy subjects were investigated. In all subjects haematocrit value, haemoglobin concentration, erythrocyte count, sodium, potassium, creatinine, iron, ferritin serum levels, total iron binding capacity, plasma renin activity (PRA), erythropoietin serum level and mean arterial blood pressure (MAP) were measured in basic conditions (normal sodium diet). Additionally PRA, EPO and MAP were measured after dietary sodium restriction to 10-20 mmol Na/24 hrs for three days and upright position of the body for three hours. Patients with HA had insignificantly lower serum EPO concentrations than healthy subjects and both studied groups did not differ in haematocrit value and determinants of iron metabolism except of significantly higher ferritin concentration in HA. After dietary sodium restriction and upright position of the body significant rise in PRA and no significant changes in EPO level were found in studied groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300563 TI - [Pathophysiologic and therapeutic aspects of electrolyte abnormalities in patients with essential hypertension]. PMID- 1300564 TI - [Reocclusion--"Achilles heel" of thrombolytic treatment in cardiac infarction]. PMID- 1300566 TI - [Personal experiences in the treatment of peritonitis with a complicated extended program of peritoneal dialysis]. AB - In 37 pts treated with peritoneal dialysis (PD) in years 1980-1990 results of peritonitis (P) treatment were compared between years 1986-90 (cycle II) and years 1980-85 (cycle I). In I cycle 47 episodes of P occurred in 9 of 21 pts treated with PD, and in cycle II 15 episodes of P in 7 of 16 dialysed pts. Treatment of P was as follows: in cycle I, daily standard PD with gentamicin and cephradine added to 2.01 dialysing exchanges; in cycle II, after initial lavage of peritoneum with a few litres of dialysing solution, 1.0 g vancomycin was given iv and continuous PD started using 1.0 litre prolonged exchanges and aminoglycosides added to dialysis solution. Treatment protocol used in cycle II was more effective than the first one: all episodes of P were immediately cured (only 32 of 47 in cycle I), there was only 1 relapse (in cycle I 6/32 cured P), duration of P was shorter (mean 6.5 days/9.8 days in cycle I) and morphological changes of peritoneum were less expressed than in cycle I. Practically important indicator of cure was decline of polynuclear cells in smear of peritoneal effluent sediment (less than 50% of cells). All 9 pts suffering from P in cycle I had to be transferred to HD (43% of all dialysed pts) and only 2 in cycle II (12% of all dialysed pts). PMID- 1300567 TI - [Efficacy of recombinant human erythropoietin (rhuEPO) in treatment of anemia in patients with myelodysplastic syndrome]. AB - This paper summarizes results of rhuEPO--treatment obtained by different authors in 27 patients with a myelodysplastic syndrome (MDS). Only 1/3 of all patients with a MDS were responsive to rhuEPO treatment, while in 2/3 of these subjects no amelioration of anaemia was noticed, even after extremely high doses of this hormone. A detailed description of a patient with MDS, which was observed by the authors, is presented. In this patient the anaemia was refractive even after very high doses of rhuEPO administered for 10 weeks. PMID- 1300568 TI - [Unusually large thrombus in the left cardiac ventricle in a patient with a history of anterior wall infarction]. AB - The giant size thrombus like a swallow's nest in the left cardiac ventricle in the patient with a history of anterior infarction was reported. In the autopsy a significant narrowing of the left coronary artery and two critical narrowings of the anterior interventricular artery were revealed. The relation between the localization of the pathological changes in the coronary arteries and the thrombi occurring during cardiac infarction was discussed. PMID- 1300565 TI - [Treatment of chronic hepatitis B with interferon alpha (Wellferon) with and without previous corticosteroid therapy -- results of a multicenter, double blind study]. AB - The present study was aimed to test the efficacy and safety of interferon alpha (Wellferon-Wellcome Foundation Ltd.) either alone, or in combination with short term corticosteroid pretreatment in the therapy of chronic hepatitis B. 44 patients with documented chronic hepatitis type B (12 women and 32 men; mean age 37.5 years, range 23-59 years) and satisfying the entry criteria were subjects of the study. 30 patients had chronic active hepatitis on liver biopsy, while 14 had chronic persistent hepatitis. Consecutive patients were given either placebo or prednisone in a double-blinded manner for 4 weeks (0.6 mg/kg/day in the first two weeks, 0.45 mg/kg/day in the third week and 0.25 mg/kg/day in the last week), and then, after a 2 week pause, therapy with interferon was instituted for a total of 12 weeks. Interferon was given by intramuscular injection in a single daily dose of 10 x 10(6) IU for 5 days and three times weekly thereafter. However, because of side effects, the dose of interferon was occasionally reduced to 5 x 10(6) IU in most patients. Interferon induced a sustained cessation of HBV replication as judged by loss of DNA-polymerase activity in 26 (59%) patients, 20 (45%) patients seroconverted to anti-HBe. Additionally, 6 (14%) cases lost HBsAg and seroconverted to anti-HBs. Prednisone pretreatment did not seem to improve the efficacy of interferon therapy. The outcome of the treatment was unrelated to gender and pretreatment activity of transaminases, however, patients with low activity of HBV replication were more likely to respond to therapy than patients with high HBV replication. PMID- 1300569 TI - [Central receptors for natriuretic peptides and their role in regulating the circulatory system]. PMID- 1300570 TI - [Non-invasive evaluation of function in both cardiac ventricles and arrhythmias in patients with dilated cardiomyopathy]. AB - Resting echocardiography with M-mode technique under the control of bidimensional picture and pulsating Doppler ultra sound and a 24-hour ECG with Holter technique were performed in 19 patients with dilated cardiomyopathy (6 females and 13 males; mean age 46 years, mean duration of the disease 23 months). A group of 7 patients with electrocardiographic features of the left ventricle hypertrophy, according to Sokolov index, was distinguished and compared with a group of patients without ventricular hypertrophy. The symptoms of pulmonary hypertension with progressing dilatation and failure of the right cardiac ventricle were found in patients with dilated cardiomyopathy without coexisting hypertrophy, despite of significant deterioration of the contractive function. Cardiac arrhythmias and thrombotic disorders which are hazardous for life were significantly more frequent (78% and 22%, respectively) in this group. Percentage of sudden deaths in these patients was high (56%). PMID- 1300571 TI - [Clinical observations and echocardiographic features of mural thrombi in the left ventricle during myocardial infarction]. AB - The incidence and changes in the mural thrombi in left ventricle in ECHO-2D in the acute myocardial infarction as well as relationship between clinical parameters and echocardiographic indices of the left cardiac ventricle contractability asynergy and dynamics of changes in mural thrombi have been investigated. The studies included 137 consecutive patients (98 males and 39 females) treated for the acute myocardial infarction. Patients' age ranged from 35 to 87 years (mean 62 years). Infarction of the anterior and/or lateral wall was diagnosed in 67 patients, and infarction of the inferior and/or posterior wall in 70 patients. Mural thrombi were diagnosed in 42 (31%) patients. Eighteen thrombi (43%) were liquefied during hospitalization. Comparative analysis of patients in whom mural thrombi underwent liquefaction in the hospital and a group of patients with myocardial infarction and persisting mural thrombi showed that return of left ventricle movements with subsequent contractability facilitate liquefaction of mural thrombi. Higher mortality rate in the group of patients with myocardial infarction with mural thrombi is due to extension of the infarction accompanied by marked asynergy of left ventricular contractions which does not decrease in sequential examinations, and increasing congestive heart failure. PMID- 1300572 TI - [Late outcome of patients with myocardial infarction complicated by mural thrombi in the left heart ventricle]. AB - The study was aimed at the evaluating of the remote clinical course and death rate in patients with myocardial infarction, in whom mural thrombi in the left cardiac ventricle were diagnosed during hospitalization. During a 24-month follow up, 23 (20%) out of 116 patients died, including 10 (43.5%) patients with myocardial infarction complicated with mural thrombi during hospitalization. There were 39% of sudden deaths. Ninety three (80%) patients, including 27 (29%) patients of the group with myocardial infarction complicated with mural thrombi in left ventricle during hospitalization, were reported for the ambulatory examination. Features of the postinfarction heart failure, cardiac arrhythmias, the second myocardial infarction or exacerbations of the coronary disease which required hospitalization were significantly more frequent in this group. PMID- 1300573 TI - [Blood viscosity factor in persons with high and low risk of ischemic heart disease]. AB - In the years 1986-1987, the blood viscosity factor, the content of haemoglobin in erythrocytes, the concentration of glucose in blood, the lipids and the blood coagulation system were examined in 180 subjects. They were divided into three groups according to the exposure to risk factors: group performing light manual work (L), group performing hard manual work (C) and group of engine drivers (M). No statistically significant differences in regard to age, employment period, number of cigarettes smoked, as well as arterial systolic and diastolic blood pressure were found between the subjects. Workers from group M had the highest body weight (P > 99%) and increased concentration in blood of triglycerides (P > 99% and Apo B (P > 99%. Subjects from group C had the lowest concentration of cholesterol in blood (P > 99%) and the smallest number of members with hypertensions (3.8%) and overweight (7.5%). Group L included the highest percentage of persons with arterial hypertension (17.5%), the highest, among all examined, blood viscosity factor determined at the coagulation rate of 18.6 s-1, and the lowest prothrombin factor (P > 99%). PMID- 1300574 TI - [Time of day and occurrence of myocardial ischemia]. AB - A 24-hour Holter ECG was registered in 130 patients with the ischemic heart disease with or without the history of myocardial infarction treated in out patient clinic. Two hundred thirty seven episodes of myocardial ischemia were detected. These episodes developed between 6.00 and 8.00 a.m., 12.00 and 4.00 p.m., and 6.00 and 8.00 p.m. PMID- 1300575 TI - [Twenty-four hour monitoring of electrocardiogram in patients with rheumatoid arthritis]. PMID- 1300576 TI - [The fate of young individuals with a history of myocardial infarction]. AB - The fate of young individuals (to 45 years) with a history of myocardial infarction during 12 years was analysed with the aid of a questionnaire containing questions of both social and medical character. Sudden cardiac death or the second infarction were the most frequent causes of death during the first two years following myocardial infarction. Change in the physical activity mainly involved the return to work. Only 47% of young men and 29.8% of women started full-time jobs. They mainly belonged to so-called white collars. The lack of patients' physicians permission was a main cause of the abstinence of young men from the occupation. A position within the family and social activity usually remained unchanged in the majority of patients, but every third patient greatly reduced sexual activity. Every third patients continued smoking, and did not observe recommended diet despite the systematical medical check-ups. The course of the disease is unclear in the majority of young patients. It is often deformed and requires further, detailed information on young patients' style of life. PMID- 1300577 TI - [Interactions of drugs used in treating diseases of circulation]. PMID- 1300578 TI - [Coexistence of von Willebrand's disease with mitral valve prolapse]. AB - The authors present the case of mitral valve prolapse. In a young woman with three-year history of systematically treated epilepsia mitral valve prolapse with a spurious string within left ventricle has been diagnosed echocardiographically in coincidence with the symptoms of haemorrhagic diathesis of von Willebrand type in form of haemoptysis and or/massive haemorrhages in mouth occasionally being preceded by heart rhythm disturbances. No local changes have been observed in otorhinolaryngologic examination, bronchoscopy and gastroscopy. Possible mutual dependence of 3 above stated abnormalities is being discussed. It is not excluded, that mitral prolapse may constitute the primary entity and epilepsia is of secondary character as a result of cerebral ischaemic incidents or of cerebral embolism. It is also a matter of discussion to what extent abrupt haemodynamic disturbances connected with critical fall of systemic blood pressure due to mitral prolapse may influence the haemorrhagic episodes. PMID- 1300580 TI - [Tachycardiomyopathy]. PMID- 1300579 TI - [Programmed electric stimulation of cardiac ventricles--hopes and limitations]. PMID- 1300581 TI - [Inotropic drugs in treatment of heart failure--advantages and adverse reactions]. AB - Mechanism of action, hemodynamic effects, efficacy of both shortterm and chronic administration of available inotropic drugs are discussed. An emphasis is on the possible mechanism of detrimental sequelae of the chronic inotropic stimulation of the failing heart. PMID- 1300582 TI - [Clinical value of transesophageal heart stimulation]. PMID- 1300583 TI - [Chamber of physicians in Poland]. PMID- 1300584 TI - [Certain aspects of acute arterial thrombosis]. AB - An analysis included 228 patients with the acute arterial thrombosis in the extremities. Over 33% of patients reported to the treatment later than 24 hours after the onset. This delay markedly worsened the results of therapy. Sixty two percent of limbs was saved. Mortality rate was 15%. The author analyse the results of therapy in relation to the localization of thrombi and type of the treatment--surgical, use of vasodilators with heparin or streptokinase. In case of thrombosis localized in the end segment of aorta the results were less promising than in case of more peripheral arterial involvement. Excellent and favourable results in this group amounted to 32%, the limb was amputated in 13% of patients and 28% of patients died. Hundred eighty patients were operated. Arteriosclerotic lesions to the arterial wall were detected in 97%. Excellent and favourable results of surgery were achieved in 45%, amputations amounted to 22%, and mortality rate was 16%. Vasodilators combined with heparin produced an improvement in 13% of patients in whom surgery could be postponed. The best results were achieved in patients treated with fibrinolytic agents with subsequent surgery or without it. In this group excellent and favourable results amounted to 57%, amputations--24%, and mortality rate--8%. PMID- 1300585 TI - [Dissecting aneurysm as a cause of acute non-traumatic ischemia of the lower limbs]. AB - The results of the treatment the acute non-traumatic ischemia of the lower limbs caused by dissecting aneurysm are discussed. Out of 726 analysed patients 8 of them suffered from dissecting aneurysm, i.e. 1.1%. Dissecting aneurysm was more frequent in male patients. All patients with lower limbs ischemia caused by the dissecting aneurysm were operated. Vascular prosthesis was used in 6 cases, and restoration of arterial patency in 2 cases. Seven patients died during the early postoperative period and one was released home with proper blood flow. PMID- 1300586 TI - [Early results of acute non-traumatic ischemia of the limbs]. AB - The results of therapy of 726 patients with the acute non-traumatic ischemia of the limbs are discussed. These patients were treated in the 11 centres of vascular surgery in Poland between 1986 and 1988. Out of causes of the acute non traumatic ischemia of the limbs arterial embolism was diagnosed in 450 patients, thrombosis in 229 cases, and dissecting aneurysm in 8 patients as well as phlegmasia coerulea dolens in 1 patient Surgical treatment included 665 patients, and the remaining 383 patients were treated conservatively. The results of the conservative and surgical treatment were scored with a 5-point scale. Excellent results with the return of complete functioning of the affected limb and presence of peripheral pulse were achieved in 291 patients, positive result, i.e. lack of the peripheral pulse, in 197 cases, moderate result in 80 patients in whom complete functioning of the limb has not been restored. In case of 64 patients an amputaion proved necessary. Nine four patients died. PMID- 1300587 TI - [Thrombolytic therapy in arterial thrombosis producing acute ischemia of the lower limbs]. AB - Efficiency of the thrombolytic therapy in the acute arterial thrombosis (producing an acute ischemia of the lower limbs) with streptokinase has been assessed in 35 patients treated in the selected departments of vascular surgery in Poland. Complete recovery has been noted in 9 patients (25.7%) in whom limb functioning with detectable peripheral pulse have been restored. An improvement has been achieved in 12 (34.3%) patients and moderate result in 4 (11.4%) patients. The limb has been amputated in 7 (20%) patients, and 3 patients (8.6%) died. Similar results have been observed in case of ischemia of duration period below 12 hours, between 12 and 24 hours, and between 24 and 72 hours. The results have been worse when thrombolytic therapy was introduced after 72 hours. PMID- 1300588 TI - [Differentiating the causes of acute non-traumatic ischemia of the lower limbs]. PMID- 1300589 TI - [Clinical assessment of treatment results for atherosclerotic ischemia of the lower extremities with intraarterial ozone injections]. AB - Ten injections of O3 into femoral arteries were administered to 50 patients with atherosclerotic ischemia of the lower extremities and to 49 diabetic patients. All patients were assessed clinically with the ankle-arm index, measurement of intermittent claudication distance prior to and after the treatment. The treatment showed a significant improvement in both groups manifested by an increase in ankle-arm index, and prolongation of the intermittent claudication distance by more than twice. The treatment of atherosclerotic ischemia of the lower extremities with O3 is both valuable and safe. PMID- 1300590 TI - [Early and late results of treating peripheral arterial injuries]. AB - Forty six patients with injuries to the great peripheral arteries were treated at the III Department of Surgery, Medical Academy in Cracow in 1968-1987. An injury to the blood vessels was accompanied by bone fractures or joint dislocation in 9 (19.5%) patients whereas 35 (76%) patients suffered also from vein injuries and nervous trunks trauma. In 13 (28%) cases an accident took place when the victims were drunk. Favourable result of the treatment, i.e. return of peripheral pulse, was achieved in 33 (75%) patients, acceptable result, i.e. an increase in limb temperature, in 11 (23%) patients. Two patients underwent an amputation of the limb because of its necrosis. One patient died. Anti-thrombolytic agents were given intra- and postoperatively, and in 9 patients with extensive contusions fasciotomy proved successful. Late results were similar to early ones. PMID- 1300591 TI - [Clinical significance of modulating homocysteine metabolism]. PMID- 1300592 TI - [Evaluation of results of early excision of necrotic tissue in severe burns from clinical and experimental material]. PMID- 1300593 TI - [The value of doppler ultrasound in diagnosis of internal carotid artery disease]. PMID- 1300594 TI - [Biernacki's test and its development in the past century]. PMID- 1300595 TI - [Informing the patient about his disease in the opinion of Polish and German students of medicine]. PMID- 1300596 TI - Immunohistochemical analysis of the distribution of a breast tumor associated antigen recognized by a monoclonal antibody. AB - A new monoclonal antibody (MoAb), MM 1-80, recognizing a tumor associated epitope of a breast high molecular weight mucin molecule was tested, using the avidin biotin immunoperoxidase method on normal and pathological mammary tissues. The normal mammary ducts and lobules were negative. Fibroadenomas showed a strong intracytoplasmic staining. In apocrine metaplasia, adenosis, and papillomatosis, scattered cells showed intracytoplasmic, luminal border or secretion reactivity. In lobular and ductal hyperplasia the cells showed intracytoplasmic immunoreactivity which, however, became more intense and homogeneous in atypical lesions, i.e. lobular and ductal in-situ carcinomas. The infiltrating carcinomas of different histotype expressed positivity on 98% of the cases (113/115) and axillary metastatic lymph nodes were always positive (20/20). The MoAb was tested on 175 human neoplasias of different origin which were in the majority of the cases negative with the exception of adenocarcinomas of the lung, ovary and bladder. MM1-80 appears to react preferentially with mammary cells undergoing hyperplastic, metaplastic and neoplastic processes. The 1-80 epitope distribution is different in these lesions starting with a predominant luminal expression in benign lesions and becoming strong and cytoplasmic in the malignant breast cell. PMID- 1300597 TI - Correlation of nucleolar organizer regions and nuclear morphometry assessed by automatic image analysis in breast cancer with aneuploidy, K167 immunostaining, histopathologic grade and lymph node involvement. AB - Silver-stained nucleolar organizer regions (AgNORs) in human breast carcinoma were studied using a computer-assisted system of image analysis. Standardized, automatic measurements of 7 morphometric parameters (area, perimeter, shape factor, bend energy, angle, and small and large diameters) performed on paraffin sections and cell imprint were compared and correlated with nuclear morphometry, histopathological grading, tumor growth fraction, (monoclonal Ki67 immunostaining), DNA nuclear content (stoechiometric Feulgen staining) and axillary lymph node invasion. The major findings were as follows: (i) variations in AgNORs and nuclear parameters were correlated, (ii) the ratio of AgNOR area/nuclear area was significantly different in low and high grade tumors, (iii) mean AgNOR parameter values increased significantly with the tumor growth fraction and tumor hyperploidy and were significantly higher in patients with axillary lymph node metastases and (iv) AgNOR evaluation was more accurate for cell preparations than for tissue sections. PMID- 1300598 TI - Adenomas arising in Barrett's esophagus with adenocarcinoma. Report of three cases. AB - Adenocarcinoma of the esophagus is a well known complication of Barrett's esophagus, and results from a dysplasia-carcinoma sequence. This report describes 3 patients with adenomatous polyps arising in Barrett's esophagus. One patient presented with multiple sessile or pedunculated polyps giving a polyposis appearance; the other two patients had single polyps associated with distinct adenocarcinoma arising in Barrett's esophagus. Polyps consisted of adenomatous proliferation with adenocarcinoma in the 3 patients. Review of the literature identified twelve previously reported cases. These cases show that although rare, adenomas may arise in Barrett's esophagus, and are most likely premalignant lesions such as other adenomas of the gastrointestinal tract. PMID- 1300599 TI - Electron microscopic study on cell-to-cell interactions in oral lichen planus. AB - Ultrastructural analysis of oral lichen planus was performed in 18 cases, focusing on cell-to-cell interactions. In the peripheral portion of the lesion, the most consistent findings were a widening of intercellular spaces, separation of the basement membrane (BM) from basal cells and scarce inflammatory cells. In the central portion of the lesions basal cells and BM showed severe damage and numerous inflammatory cells infiltrated into both the epithelium and subepithelial stroma. The infiltrates predominantly consisted of T-lymphocytes, a few Langerhans cells (LC) and macrophages. Most lymphocytes were large and positive for CD45RO. Dendritic LC and macrophages with cytoplasm containing abundant organelles were seen in the epithelium and subepithelial stroma, respectively. Close contacts of lymphocytes with LCs, macrophages and also with keratinocytes were sometimes observed in the central portion. In the subepithelial stroma, some lymphocytes contacted an HLA-DR+ dendritic cell, which was possibly a macrophage, forming a rosette-like arrangement. Conjugations between CD4 cells and dendritic cells (possibly LC) and also between CD8 cells and basal cells were observed in the epithelium. These T cells were large in size, and the CD8 cells which made contact with degenerated keratinocytes possessed cytoplasm containing numerous polarized organelles and a nucleus toward and contrary to the contact side, respectively. These lymphocytes expressed LFA-1 on the cell surface, and many basal cells exhibited ICAM-1. These findings indicate that T cells may receive information from LC and macrophages concerning degenerative keratinocytes, and that informed T cells attack perhaps the keratinocytes. PMID- 1300600 TI - Histomorphometry in paraffin sections of thyroid tumors. AB - Planimetric features of cell nuclei in paraffin-embedded histological sections of benign and malignant thyroid tumors, as well as normal thyroid tissue as control, were determined by means of a semiautomatic system. The main aim was to objectify possible quantitative differences between adenomas and carcinomas of the thyroid gland, which had recently been reported by several authors. For each nuclear profile, the area, the maximum diameter as well as two form factors were calculated. Statistical analyses of morphometric differences between normal controls, oxyphilic adenomas and carcinomas, and between follicular adenomas and carcinomas were performed using the T-test, a multivariate test, and a discriminant analysis. The tests revealed significant differences between controls and all other groups. The most striking result, however, was the total discrimination between follicular adenomas and carcinomas, with no false reclassification. Carcinomas had a higher mean nuclear area and diameter and a lower form factor. A similar reliability of discrimination could be obtained by comparing these morphometric values in oxyphilic adenomas and carcinomas. When using a test set of 9 cases (4 adenomas, 5 carcinomas), only one adenoma was falsely reclassified as a carcinoma by the discriminant analysis. Our results thus allow the conclusion that planimetric nuclear measurements indeed seem to be useful for the objectivation of cytomorphologic differences between adenomas and carcinomas of the thyroid gland. PMID- 1300601 TI - Fibrous hamartoma of infancy. A study of eight cases with immunohistochemical and electron microscopical findings. AB - Eight cases of fibrous hamartomas of infancy are presented. Actin positivity and desmin negativity in collagen forming spindle-shaped cells and electron microscopical findings point to the myofibroblastic nature of this entity. "Dark cells" which spread regularly in all but one of our tumors were immunohistochemically determined to be a mixture of B and T cell lymphocytes. Their selective location and possible role are discussed. PMID- 1300602 TI - Myofibroblastic pseudotumor mimicking epididymal sarcoma. A clinicopathologic study of three cases. AB - The clinical and pathologic features of three cases of epididymal pseudotumor are described with emphasis on its differential diagnosis and histopathogenesis. The first lesion was found histologically worrisome in the region of ductus epididymis by a torsioned testis in an 8-month-old boy, although the lesion was clinically indistinctive, and grossly not remarked. Histodiagnostic difficulties are encountered because this lesion forms numerous infiltrative spindle cells in haphazard arrangement. Ultrastructurally, the cell components of this lesion are predominantly myofibroblasts, intermediate cells between fibroblasts and myocytes. Similar epididymal lesions with the same cell components were identified in the two other infantile cases on the review of 36 consecutive orchiectomy specimens all obtained for testicular torsion. These three boys were found to present with a relatively gradual clinical course of the testicular torsion. It is suggested that myofibroblastic proliferation in the epididymal location histologically reminiscent of sarcomas occurs under ischemic circumstances. PMID- 1300603 TI - Giant cell granuloma of the lung. AB - In a 50-year-old man without bronchopulmonary symptoms a round mass lesion close to the hilum of the right lung was detected in a routine chest x-ray and confirmed by computed tomography. Histological examination of two biopsy specimens did not result in a definitive diagnosis. Therefore thoracotomy with enucleation of the focus was performed. The histological picture of the lesion is characterized by connective tissue proliferation, multinucleated giant cells, ossification, localised hemorrhage, deposits of hemosiderin and foci of foam cells. The findings are interpreted as a giant cell granuloma of the lung. PMID- 1300604 TI - Granular cell tumor in differential diagnosis of tumors of the breast. The role of fine needle aspiration cytology. AB - The granular cell tumor (GCT) represents a rare but important lesion in the differential diagnosis of breast tumors. Since this generally benign tumor may be misdiagnosed as malignant in clinical investigation, mammography, sonography, and even in frozen sections, a preoperative diagnosis is of utmost importance. Two cases illustrate that fine needle aspiration cytology (FNAC) may be the method of choice in achieving a correct preoperative diagnosis. The histogenesis of GCT is examined by means of immunohistochemical stainings. The results confirm that this tumor arises from the peripheral nerve tissue. Most likely the Schwann cells and not the nerve cells constitute the origin of GCT. PMID- 1300605 TI - Extra-adrenal pheochromocytoma-ganglioneuroma. A case report. AB - A case of rare extra-adrenal tumor composed of pheochromocytoma-ganglioneuroma which developed in a 48-year-old Japanese male is reported. Histologically, the tumor contained equal proportion of two distinct patterns, pheochromocytoma and ganglioneuroma. Immunohistochemical examination revealed that pheochromocytoma cells were positive for Leu-7 and ganglion cells in ganglioneuroma were positive for vasoactive intestinal peptide (VIP), respectively. Neuron specific enolase (NSE) was positive in the neoplastic cells of both components, and S-100 protein was also positive in fibers around ganglion cells. Ultrastructural examination revealed that neurosecretory granules were present in the neoplastic cells. PMID- 1300606 TI - What's new in the role of cytokines on osteoblast proliferation and differentiation? AB - This review assesses recent data concerning the role of cytokines produced by a variety of cells in bone on osteoblast function. The following themes are presumed: (1) osteoblasts are mesenchymal cells which act as either the major cellular agents of bone formation or as modulators of bone resorption by osteoclasts. The regulation of osteoblast proliferation and differentiation may involve a negative feedback process resulting in phenotype suppression; (2) cytokines including platelet-derived growth factors (PDGF), parathyroid hormone related proteins (PTHrP), bone morphogenic proteins (BMP), transforming growth factor beta (TGF beta), fibroblast growth factors (FGF), insulin-like growth factors (IGF), epidermal growth factors (EGF), interleukin-1 and 6, tumour necrosis factors (TNF), interferon and haematopoietic growth factors have effects on osteoblast differentiation and proliferation but their effectiveness may not be identical in vitro and in vivo; (3) finally, therapeutic strategies for cytokine use in clinical practice are considered. PMID- 1300607 TI - Neurofibromatosis involving the small bowel associated with adenocarcinoma of the ileum with a neuroendocrine component. AB - A patient with neurofibromatosis involving the small bowel who developed adenocarcinoma in an area of the ileum showing diffuse involvement of the disease is presented. Unlike the five cases with this association previously described, the present case shows a neuroendocrine component within the adenocarcinoma. The relation between neurofibromatosis of the bowel wall and adenocarcinoma may be explained by a decreased intestinal transit time in this patient. The presence of a carcinoid tumor in the ileum is not unusual in a patient with von Recklinghausen's disease, although the location of the carcinoid in the duodenum is described more frequently in these patients. The appearance of endocrine/neuroendocrine features within an adenocarcinoma already involved by diffuse neurofibromatosis is exceptional and may not be a chance event. PMID- 1300608 TI - Progressive multifocal leukoencephalopathy and gliomas in a HIV-negative patient. AB - A case of progressive multifocal leukoencephalopathy (PML) is reported, detected at autopsy of a 30-year-old patient. The clinical picture was characterized by a progressive course of mental deterioration and ingravescent neurological symptoms. The patient was HIV-negative. He died of bronchopneumonia, after a clinical course of 13 months. Autopsy disclosed pulmonary tuberculosis with involvement of regional lymph nodes. In the brain, besides numerous PML-foci of varying age and structure, a pleomorphic astrocytoma was found in the white matter of the right parietal lobe. In the brain stem glial proliferation resembling diffuse gliomatosis was also present. In situ hybridization revealed Papova-virus (JCV) in oligoglial nuclei, but not in neoplastic astrocytes. This is the third report on the concomitant occurrence of PML and glioma in man. PMID- 1300609 TI - Clonal Ig-gene rearrangement in some cases of gastric RLH detected by PCR method. AB - Clonal immunoglobulin (Ig) heavy chain gene rearrangement in gastric reactive lymphoid hyperplasia (RLH) cases was investigated by means of the 'double' polymerase chain reaction (PCR) using formalin-fixed and paraffin-embedded tissue. Rearranged DNA sequences, formed by combinations of variable (VH) and joining (JH) regions, were amplified with oligomeric primers. One microgram of DNA extracted from formalin-fixed and paraffin-embedded tissue was applied as the 'first PCR' template and one ten-thousandth of the first PCR product was used as the 'second PCR' template. As a control study for the double PCR method, DNA isolated from frank B cell gastric malignant lymphomas was assessed. Clear single bands between 100 and 150 base pair markers in length were evident on agarose gel electrophoresis in 10 out of 13 cases (76.9%) of malignant lymphomas while 2 out of 22 cases (9%) of RLHs revealed clear single bands of the same length, suggesting malignant lymphomas; however, no histologic features of malignant lymphomas were present. It is concluded that even gastric RLH cases satisfying histopathologic criteria for benign lymphoid hyperplasia may contain occult monoclonal B cell populations suggesting a continuous and progressive spectrum of lesions contributing to B cell neoplasia. PMID- 1300610 TI - Intra-abdominal desmoplastic small-cell tumours with divergent differentiation. Report of two cases and review of the literature. AB - Two intraabdominal desmoplastic small cell tumours presenting in young adult males and involving the entire peritoneum, with no evident single primary site, have been studied. The histological pattern was suggestive of a metastatic small cell epithelial neoplasm, but immunohistochemical study revealed strong reactivity for cytokeratins, vimentin and desmin indicating synchronous epithelial and myogenous differentiation. In addition epithelial membrane antigen and neuron specific enolase were also positive. Electron microscopy showed fairly undifferentiated tumour cells with striking desmosome-like junctions, containing prominent paranuclear whorls of intermediate filaments, and a typical myofibroblastic stroma around neoplastic islands. Although the histogenesis of these recently described and rare tumours still remains uncertain, it seems that they constitute a reproducible entity which requires differential diagnosis from other small cell tumours of childhood and young adulthood. PMID- 1300611 TI - Langerhans cells and lymphocyte subsets in human gastrointestinal carcinomas. An immunohistological study on frozen sections. AB - In an immunohistochemical study of 38 human gastric and 40 human colonic carcinomas Langerhans cells, suppressor and helper lymphocytes were identified on frozen sections by using anti-CD1, anti-CD8 and anti-CD4 monoclonal antibodies. Tumours were divided into those with few (< 3 per high power field) and those with many (> 3 per high power field) Langerhans cells as well as into those with high number of CD4 and CD8 cells (> 30 per high power field). No significant difference in the number of Langerhans cells regarding histologic types, degree of differentiation and metastatic/non-metastatic groups of either gastric or colonic carcinomas was found. On the contrary the numbers of Langerhans cells related significantly (p < 0.05) to density of T-cell and especially CD4 cell infiltrations of gastric and colonic carcinomas. This finding supports the role of Langerhans cells as antigen presenting cells and their involvement in T-cell activation against neoplastic cells of human gastrointestinal carcinomas. PMID- 1300613 TI - Some novel applications of synthetic polymers in drug delivery. PMID- 1300612 TI - Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1). AB - An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM). PMID- 1300614 TI - [Cephalosporin antibiotics from the firm Glaxo in treatment of patients with complications after trauma]. AB - The most serious complications in the treatment of open fractures and after procedures on bone tissue are infections. The broad spectrum antibiotics are usually used in the treatment of soft-tissue and bone infections. Effect of the compound treatment with cephalosporins produced by Glaxo administrated intravenously and with Septopal-locally were estimated basing on radioisotopic bone examination. In compound treatment cephalosporins and gentamicin in form of Septopal renal function evaluation is demanded and recovery process should be documented by the radioisotopic image. PMID- 1300615 TI - [Use of septopal in treatment of serious infections of the fingers]. AB - Serious purulent infections of fingers often lead to deformation, handicap of functions or amputation of fingers. Filling the place with Gentamycin-Septopal after removing the slough and infected tissues gives high local concentration of antibiotic and regeneration of the anatomic shape of the finger. 21 patients have been treated. In all cases the wound healed quickly. The remote cosmetic results and the function of the hand were acknowledged as positive by both the patients as the treating team. PMID- 1300616 TI - [Septopal from E. Merck in the prevention and treatment of bone and soft tissue infections]. AB - On the basis of the many years usage of Gentamycin-Septopal in treatment of blood derived and traumatic inflammation of bones we can say that in both forms of inflammation fully satisfying results were achieved. In chronic traumatic inflammations of bones with active stomias where the inflammatory process lasted many weeks, and from the purulent matter two or more tribes with various sensitiveness to antibiotics, associated treatment was also used with application of large doses cephalosporin antibiotics of Glaxo-Zinacef of Fortum firms. It should be stressed that in treatment of a patient with that disease correct radioisotopic diagnostic of the focus of inflammation and the evaluation of the immunity state of the organism of the patient, especially during long-lasting disease, is, among others, important. PMID- 1300617 TI - [Radiologic evaluation of changes occurring in bone under the influence of gentamycin-septopal]. AB - On the basis of several-year experience it was acknowledged that in treatment of chronic blood-derived and traumatic inflammations of bones the introduction of chains of Septopal to treatment was an obvious progress. The changes occurring in the bones of the patients for whom Septopal was left for good in the marrow cavity under the influence of antibiotic were evaluated. The observation included 89 patients for whom X-ray examinations were made many times in various intervals. Initially the chains of antibiotic were surrounded with a thin layer of connective tissue, and after several new-generating osseous tissue grew into them. In none of the observed cases any reaction indicating recoil of the carrier of the antibiotic was noticed. PMID- 1300618 TI - [Effect of septopal on kidney function during treatment of traumatic chronic inflammation of bones]. AB - Treatments included 20 patients for whom in the marrow cavity 1 chain of Septopal was inserted, and 10 patients for whom 2-4 chains were inserted. Before the planned operation the mark of the level of urea and of creatinine in the blood serum was made for the patients, and the clearance of creatinine was calculated. It was stated that usage of Gentamycin-Septopal for people who do not let know about the suffering from a kidney disease in the past, and the laboratory tests before the operation do not show deviations from the standard is a safe treatment recommended in prophylaxis and in treatment of blood-derived and traumatic inflammations of bones. Because of nephrotoxicity of Gentamycin the function of kidneys should be monitored before and during treatment with that medicine. Gentamycin can be connected with other antibiotics in order to improve the efficiency of its work. PMID- 1300619 TI - [Use of septopal in treatment of acute blood-borne inflammation of bones in children]. AB - The authors are presenting 70 cases of acute blood-derived inflammation of bones in children treated in the Clinic of Children's Surgery in the Academy of Medicine in Wroclaw in the last 10 years. Gentamicin balls were used for 21 children including 18 newborns and babies. In 16 cases implantation of gentamicin balls was the only way of local treatment, and in 5 cases it was preceded with short-lasting (3-7 days) flowing drain of the inflammatory focus. Implantation of gentamicin balls was renewed after 14-18 days achieving in all cases sterilization of the inflammatory focus within the bone. The applied treatment allowed to reject quickly the general antibiotic therapy. After operational course for all children was normal. PMID- 1300620 TI - [Application of mini-septopal in surgery of the hand]. AB - Successful application of the Septopal in treatment of osteomyelitis has created the demand for this form of drug available for implantation into the small operation field, e.c. in the hand. The Chair and Clinic for Traumatology of the Medical Academy in Wroclaw has been chosen to cooperate in the clinical trial on application of the Septopal-minichains in surgery of hand. There were 76 patients treated with the Mini-Septopal implantation. In 18 cases the osteomyelitis or active bacterial soft tissue infection gave indications for this type of treatment. In 58 cases Mini-Septopal was implanted because of high risk of infection in contaminated wounds. In both groups bacteriological examinations have been performed and statistical study revealed successful results even in primary resistant for gentamicin bacteries. Very good results of treatment let us estimate very high the usefulness of Mini-Septopal in bone and soft-tissue infections treatment, if the proper surgical procedures are performed to clean the focus of infection. PMID- 1300621 TI - Patient-centered health care: desideratum for medical care reform. PMID- 1300622 TI - Changes in knowledge, attitudes and behavior of women participating in a community outreach education program on breast cancer screening. AB - A community-based intervention project on Long Island was supported by the National Cancer Institute to increase the use of mammography and breast physical examination among older women. During a 1-year period 526 women aged 50 and older attended educational sessions presented by the project staff conducted in the community in a variety of settings. Sixty-eight percent (355) of the women who participated provided identifying data and completed pre- and post-session surveys while 40% (210) also completed a mail survey 6-12 months later. Screening behavior improved subsequent to the intervention, at follow-up 61% had taken some related action. More than half of the 109 women who had a mammogram after attending the session indicated that the presentation influenced them to do so. The use of a game created a positive atmosphere for conveying information about a sensitive subject and encouraged discussion among women who had a variety of experiences with screening. PMID- 1300623 TI - Reasons related to adherence in community-based field studies. AB - This study identified participants' reasons for good, marginal or poor adherence, or withdrawing from community-based clinical studies using a dietary and/or drug intervention. Adults aged 48-75 years participated in one of three studies related to decreasing colon polyp recurrence. Qualitative data from progress notes (N = 675) and end-of-study evaluations (N = 87) were coded using constant comparative analysis with 100% content validity panel agreement. Most common reasons for non-adherence were barriers such as side-effects, interference with vacation plans, unrelated illness, forgetting and competing outside stressors. Participation motivators were benefits such as altruism, medical benefits, free service and staff rapport. Findings supported the Health Behavior in Cancer Prevention model-based approach to adherence interventions and provided directions for adherence promotion in future community-based clinical studies. PMID- 1300624 TI - Patient education and compliance: a pharmacist's perspective. AB - Pharmacists are becoming more involved with patient education due to the increased emphasis being placed on primary patient care. Existing research in the area of patient education and compliance can provide pharmacists with the knowledge to enhance patient compliance. Changing noncompliant behavior can make a positive impact on patient's treatment plan. Such interventions involve the education of patients, whether it be during an outpatient consultation session or an inpatient education program. Of the five compliance theories identified in the literature, the Communication Model describes the best mechanism for pharmacists to educate their patients. During consultation sessions, essential knowledge and skills can be communicated to the patient that will maximize compliance. Monitoring medication refills is the most accessible method for pharmacists to identify noncompliant behavior. Determining patient noncompliance and making adjustments with patient education tactics will enable pharmacists to expand their professional role while improving patient outcomes. PMID- 1300626 TI - Pupil's knowledge about health and illness. AB - Three hundred twenty high school pupils were evaluated concerning their knowledge about health and disease. The knowledge of 170 students in the first school in which they received lectures and had regular talks about health topics was higher in comparison with the knowledge of 150 students in the second high school who did not receive these lectures. We recommended that health topics be integrated in the school program starting at the first grade and continuing until graduation from high school. PMID- 1300625 TI - Registered dietitians' teaching and adherence promotion skills during routine patient education. AB - Even following education sessions, dietary adherence among medical patients is generally poor. One contributor to this problem may be the quality of teaching and adherence promotion skills employed by Registered Dietitians, whose behavior during routine patient interactions was evaluated in this observational study. Thirty dietitians were videotaped with one of their patients. Twenty operationally defined skills were rated on a scale from 0 (skill absent) to 3 (excellent). Dietitians' interpersonal skills were good (mean = 2.1, S.D. = 0.35), but all other skills were performed significantly less well (mean scores less than 1.0). Adherence promotion skills were rarely observed. Dietitians need supplemental training to improve teaching and adherence promotion skills. PMID- 1300627 TI - Cigarette smoking among youth--United States, 1989. PMID- 1300628 TI - Cigarette smoking among adults--United States, 1988. PMID- 1300629 TI - Cigarette smoking among reproductive-aged women--Behavioral Risk Factor Surveillance System, 1989. PMID- 1300630 TI - Inoculation of C6 glioma cell suspension into the brain of adult rats: morphological study. AB - The C6 astrocytoma cell line was inoculated intracerebrally as suspension into the rat brain. Tumors were allowed to grow 2 to 60 days and their development was studied on coronal sections at these survival times. Tumor cells developed intraparenchymal solid tumor at the implantation site. C6 cells also filled out the needle track-area and spread into meninges. At 2 days postimplantation (2 DPI), tumor cells were observed to infiltrate recipient's brain directly from the implantation site or via perivascular spaces of adjacent cerebral blood vessels. Some cells escaped from the implantation channel during transplantation. They spread diffusely via cerebrospinal fluid (CSF) in leptomeningeal regions over the brain surface. At 10 DPI, the tumor mass invaded the adjacent brain parenchyma as well as cerebral ventricles (CV) and C6 cells could spread intraventricularly. At 30 DPI, tumor extremely increased its size and its growth was expansive. It exhibited areas of necrosis and later on, at 60 DPI, inoculated rat brains revealed large empty pseudocysts resulting from decay of necrotic tumor masses. PMID- 1300631 TI - Transplantation immunology of the brain as a privileged site for neural grafting. AB - The course of intracerebral transplant rejection differs from rejection of grafts placed elsewhere in the body. There are many factors which may modulate immune responses in the central nervous system (CNS). Low expression of major histocompatibility gene complex (MHC) products on nervous tissue and the existence of the blood - brain barrier (BBB) seem to be the central components of this immune protection. Lymphatic drainage of the brain is limited, yet antigens introduced into the brain are drained to the lymph nodes. Some investigators highlight a lack of dendritic cells in the CNS, however, microglia, astrocytes and probably endothelial cells may act as antigen presenting cells in certain circumstances. Brain residual perivascular macrophages found in the Virchow-Robin spaces may be also involved in the process of graft recognition and rejection. Some neural cells (e.g. astrocytes) produce local immunosuppressive factors which may also contribute to prolonged neural graft survival. All these factors are not able to protect neural allo- and xenografts from rejection response. The rejection of neural intracerebral allo- and xenografts occurs suggesting the brain immune privilege is not absolute. PMID- 1300632 TI - The effects of chelating agents on the left ventricular dP/dtmax. of the paced and non-paced heart in rabbits in vivo. AB - The effects of i. v. administration of Na2H2EDTA and a novel chelator MgNa2EDTA (both drugs in doses of 0.05 and 0.1 mg. kg-1) on the left ventricular dP/dtmax. of the paced and non-paced heart were investigated in rabbits in vivo. Both chelators induced a decrease in cardiac contractility which was, especially after the lower doses of the drugs, significantly less pronounced after MgNa2EDTA (max. 69.6% in the non-paced and 75.2% in the paced heart) in comparison with Na2H2EDTA (max. 51.3% in the non-paced and 52.9% in the paced heart). The decrease in dP/dtmax. was similar both under the paced and non-paced heart conditions after administration of both doses of the drugs. On the basis of the results obtained, it is possible to assume that the negative inotropic effects of the new chelator MgNa2EDTA may be lower in comparison with those of Na2H2EDTA and that cardiac pacing does not influence the inotropic response to the chelators in a negative manner. Premature deaths of a number of animals after the administration of both chelators show a necessity of further studies concerning especially cardiac intracellular ion concentrations. PMID- 1300633 TI - An evaluation of continual determination of blood cholinesterase activity for inhibition studies. AB - Simple method of continual monitoring of the rat blood cholinesterase activity in vivo was used to demonstrate its inhibition following i. m. administration of acridine and carbamate inhibitors. Another type of inhibition was demonstrated for different routes of administration of highly toxic organophosphate, VX. Reactivation of the blood cholinesterase was also monitored following intoxication with VX and soman and treated with obidoxime and atropine. This continual determination of cholinesterase activity represents an useful approach to study effects of cholinesterase inhibitors. PMID- 1300634 TI - 2-Dialkylaminoalkyl-(dialkylamido)-fluorophosphates: acute toxicities. AB - Toxicities expressed as LD50 values of 2-dialkylaminoalkyl-(dialkylamid) o fluorophophates for rats and mice (i. m. administration) were determined. Rats were more sensitive to these compounds than mice: LD50 values varied from 17 to 261 micrograms/kg for rats and from 30.5 to 1222 micrograms/kg for mice, respectively. Different routes of administration in one derivative of this group substituted by methyl groups only were compared. The highest toxicity (lowest LD50 value) in intravenous administration (11 micrograms/kg) and the lowest one in percutaneous (1366 micrograms/kg) were found. PMID- 1300635 TI - Cuticular spinning structures reveal evolutionary relationships in araneomorph spiders. AB - The present paper reviews the results from the study of spigots, i.e. cuticular spinning structures obtained by the scanning of 52 genera belonging to 28 families of araneomorph spiders. The finding of eight morphologically different forms of these structures being attached to ducts of the pyriform type of silk glands is of fundamental importance for the final conclusions. The comparative observations enable me to create a hypothesis dealing with the existence of several evolutionary lines of spiders, each of which is represented with their own form of spigots. Nevertheless the character of these spigots undoubtedly reflects phylogenetic relationships between the spider taxa. The detection of a special mechanoreceptive field on top of the anterolateral spinnerets increases the knowledge of the functional morphology of the spider's spinning apparatus. PMID- 1300636 TI - [The use of Latin in German scientific language]. AB - Science is of international nature. The development of technical languages in the individual branches of science is connected with frequent borrowing of foreign language lexical material which is mostly of Latin or Greek origin. Latin has had an effect on vocabulary, word formation and syntax. The existence of a foreign scientific language above a national one is the main cause of the frequent penetration of foreign and borrowed words into German. Greek and Latin represent the traditional language material to be used in medical terminology. In scientific communication, Latin and Greek terms and also equivalents in a native language are used. PMID- 1300637 TI - [The role of ultraviolet rays in the etiopathogenesis of malignant melanoma]. AB - The aim of the study was to elucidate the role of UV radiation in the etiology of malignant melanoma within the conditions of East Bohemia region. In selected patients with malignant melanoma, anamnestic data pertinent to the frequency of sun-bathing as well as a bulk of the occupational indoor exposures brought about the action of UV-light artificial sources have been withdrawn from past history. Constitutional features for suspected photosensitivity such as the fair skin complexion and skin phototype, were investigated. The object of assumption was also the site of anatomical localization (i. e. body site distribution) of primary malignant melanoma. In a selected group of patients, routine phototesting followed by the above-threshold skin phototests were carried out with the aim to assess the capacity of reparative processes essentially occurring in the irradiated skin. In the epidemiologically oriented part of study, presumable relationships between the year's maxima of sunlight radiation and the increases in the incidence of malignant melanoma were treated statistically. It followed from the results obtained that sunlight itself is not a decisive factor and cannot explain an increased incidence of malignant melanoma in East Bohemia region. PMID- 1300638 TI - SSI case closures. AB - In 1990, about 800,000 persons receiving payments from the Supplemental Security Income (SSI) program had their cases closed and their payments stopped. The most frequently cited reasons for these case closures were excess income and death. Of those cases closed for reasons other than death, about 43 percent eventually returned to payment status. This study presents an analysis of a 1-percent sample of SSI recipients whose cases were closed during 1990. Longitudinal data on closures were collected by merging a series of monthly 1-percent sample files containing SSI administrative data. These are the first published data on reasons for SSI case closures. PMID- 1300639 TI - SSI Modernization Project. Final report of the experts. PMID- 1300641 TI - Developments and trends in Social Security, 1990-1992: overview of principal trends. AB - The article that follows is a reprint of Part I of a report presented by Dalmer D. Hoskins, Secretary General of the International Social Security Association (ISSA), to the organization's XXIVth General Assembly (November 1992, Acapulco). It identifies and interprets the major trends currently influencing the evolution of social security programs around the world, and analyzes these developments against the backdrop of the current economic, demographic, and social environment in which these programs operate. (Part II of the report analyzes the changes according to each major branch of social security; an annex to the report provides more detailed information and source citations in reference to these changes.) The ISSA is a nongovernmental international organization headquartered in Geneva, Switzerland. It is made up of 321 social security-related institutions, including the U.S. Social Security Administration, in 122 countries. The Association's aim is to protect, promote, and develop social security worldwide. PMID- 1300640 TI - The development and history of the poverty thresholds. AB - In recent years there has been renewed interest in the United States in the definition and measurement of poverty. In early 1992, the Committee on National Statistics of the National Academy of Sciences began a 30-month study requested by Congress that includes an examination of statistical issues involved in measuring and understanding poverty. Some 2 years earlier, in January 1990, the Administration had approved an initiative on improving the quality of economic statistics. The current poverty measure was one of several dozen statistical series examined as part of that initiative. In April 1990, Urban Institute economist Patricia Ruggles published a book that urged the revision of the poverty line to reflect changes in consumption patterns and changing concepts of what constitutes a minimally adequate standard of living. In July 1990, two private organizations concerned with the poor and the elderly issued a report reviewing current poverty measurement procedures and describing a Gallup poll in which a nationally representative sample of Americans set an average dollar figure for the poverty line that was higher than the current official poverty line. In view of these and other examples, it may be useful to reexamine the development and subsequent history of the current official poverty thresholds. PMID- 1300642 TI - The development and use of industry data by the Social Security Administration. AB - Over the past few years the Social Security Bulletin has published a series of technical articles that describe various Social Security Administration (SSA) data files. This article provides an overview of SSA's industry-related data files and statistical systems from both a current and a historical perspective. The author begins by explaining how SSA first collected business data from employers (starting in 1937) as a by-product of the requirement that employers report employee wages for benefit computation purposes. She describes the administrative methods by which the data are collected, SSA's coordination of its activities with other agencies, the data collection forms used, the scheme by which the data are coded, and the employer files into which the data are classified. In her closing, the author provides examples of the various uses of the industry data and the ways that these data relate to SSA's statistical program needs and to those of other agencies as well. PMID- 1300644 TI - [Nurse's story: Margrethe's death]. PMID- 1300643 TI - [Departmental management--partnership]. PMID- 1300645 TI - [Ergonomics--a healthy lifting culture]. PMID- 1300646 TI - [Senile dementia--in a home community with support]. PMID- 1300647 TI - [Executive Board. Service level politically established]. PMID- 1300648 TI - [Executive Board. Call for action plan for the work environment]. PMID- 1300649 TI - [Executive Board. We must learn to tackle violence]. PMID- 1300650 TI - [Executive Board. Modest excess revenue but more members]. PMID- 1300651 TI - [Somalia--in the midst of war]. PMID- 1300652 TI - [Historic--everyone is interested]. PMID- 1300653 TI - [SSN (Scandinavian Nurses' Cooperation)--status of assistance to the East]. PMID- 1300654 TI - [SSN--advocate for nursing. Interview by Kirsten Bjornsson]. PMID- 1300655 TI - [Nursing story. Mailbox conversation]. PMID- 1300656 TI - [Psychiatric--free room to play]. PMID- 1300657 TI - [Czech--don't forget the revolution. Interview by Mette Engell Friis]. PMID- 1300658 TI - [Czech--we trust in the future. Interview by Mette Engell Friis]. PMID- 1300659 TI - [Informatics. Data must be comparable]. PMID- 1300660 TI - [Invisible harm]. PMID- 1300661 TI - [Personnel policy--an embarrassing affair]. PMID- 1300662 TI - [Quality assurance--health care as a product]. PMID- 1300663 TI - [India: an expensive and dangerous drug]. PMID- 1300664 TI - [Health care--network in a new culture]. PMID- 1300665 TI - [A knife in the soul. Interview by Mette Fjordbo]. PMID- 1300666 TI - [Ethical code of the police]. PMID- 1300667 TI - [Conflict in the law]. PMID- 1300668 TI - [Poorly prepared in dangerous situations]. PMID- 1300669 TI - Incidence of transient bacteremia following dental surgery--prophylactic use of cefuroxime, ceftriaxone or clindamycin. AB - The incidence of transient bacteremia after dental surgery as examined in 15 ml of venous blood has been previously found to amount to 69%. In this study, cefuroxime (1.5g), ceftriaxone (1.0g) or clindamycin (0.6g) was used for chemoprophylaxis to investigate the rate of transient bacteremia after dental surgery. The concentrations of these antimicrobial agents in peripheral blood and an effusion from the tooth extraction wound were measured. The incidence of transient bacteremia was limited to 4.2% by cefuroxime, 0% by ceftriaxone and 5.9% by clindamycin. PMID- 1300670 TI - A corrected transposition of the great arteries with situs inversus visceralis and cleft palate, but without other cardiac defects. AB - A 17-year-old female admitted for cleft palate surgery was referred for further evaluation of her cardiac condition. The patient had been diagnosed as dextrocardia at birth, without any cardiac murmurs. She has led a normal life. The apical impulse was felt at the fifth intercostal space at the right mid clavicular line. The ECG and chest x-rays were strongly suggestive of corrected transposition of the great arteries (CTGA) with situs inversus visceralis. Findings of the two-dimensional and Dopplar echocardiograms showed CTGA with a mild morphologic tricuspid regurgitation without any other complicated cardiac anomalies. In the Japanese literature, 36 CTGA patients without associated cardiac defects have been reported. Of these, four patients revealed dextrocardia. To our knowledge, our patient is the first reported adult case without any cardiac defects, only minimal tricuspid regurgitation, situs inversus totalis and cleft palate. PMID- 1300671 TI - Accidents in childhood. Review of cases in the emergency room and hospitalized cases. AB - Accident mortality in childhood is a big problem not only in Japan but also in many other countries. We have reviewed our experience of 4,502 patients below 18 years of age who visited our emergency room in the fiscal year 1990. The number of cases of accidents other than traffic accidents was 243 and was almost double the 131 children involved in traffic accidents. Children with ordinary injuries (trauma) were excluded from accident patients. The most common non-traffic accident in childhood was foreign body ingestion or inhalation. The gastrointestinal tract was the most common site of foreign body ingestion or inhalation. Forty-two children with bronchial foreign bodies and 38 cases of near drowning who were admitted to our hospital from 1975 to 1991 were also studies. Among the bronchial foreign bodies, we had a high rate of peanut inhalation. Foodstuffs including peanut accounted for more than 80% of the bronchial foreign bodies. Among the 38 near-drowning cases, we had five fatal cases, three cases were severe neurological sequelae and 30 intact survivals. Bathtubs at home were the most common site of near-drowning, particularly for young children. PMID- 1300672 TI - Two cases of adenolipoma of the breast. AB - Adenolipoma of the breast is a rare tumor. Two cases are described here and the literature is reviewed. Case 1 was a 52-year-old woman who had a 3-cm-long elastic hard tumor in the left breast. Case 2 was a 40-year-old woman who had a 3 cm-long elastic soft tumor in the left breast. In each case, mammography revealed well demarcated soft tissue density. Ultrasonography demonstrated well defined tumors composed of echogenic and sonolucent areas. These tumors were easily enucleated at surgery. Histologically, the tumors consisted of mammary ducts, fibrous stroma and adipose tissue, findings which are characteristic of mammary adenolipoma. An adenolipoma may still be misdiagnosed as a fibroadenoma or a fibrocystic disease. Characteristic findings of mammography and ultrasonography are emphasized. PMID- 1300673 TI - Wood stove effects on indoor air quality in Brazilian homes: carcinogens, suspended particulate matter, and nitrogen dioxide analysis. AB - The effects of wood burning stoves on indoor air quality was investigated in a rural community of southern Brazil, during the winter season of 1991. The concentrations of polycyclic aromatic hydrocarbons (PAHs), nitrogen dioxide (NO2) and suspended particulate matter (SPM) were assessed in houses with wood stoves and the results compared with levels found in houses with gas stoves. Strikingly higher (p < 0.01) levels of PAHs, and much higher (p = 0.07) levels of SPM were found in the kitchens with wood stoves. In contrast, NO2 concentrations in the kitchen as well in personal exposure, were found to be slightly higher in houses with gas stoves. All these differences were minimally affected by smoking, outdoor air pollution or other emissions from indoor combustion products. These findings appear to support the hypothesis that domestic wood burning stoves are risk factors for some upper digestive and respiratory tract cancers in Brazil. PMID- 1300674 TI - Sickle cell disease in the Sudan. Clinical and biochemical aspects. Minireview based on a doctoral thesis. PMID- 1300675 TI - Assessment of speech and language skills in children. AB - A speech and language assessment procedure was developed to study different aspects of speech and language skills in children 6.5 years old who had needed intensive care in the neonatal period. It was required that the procedure could be carried out at one examination session and that it should characterize a broad spectrum of language skills and permit detection of deviations in language development. The assessment comprises three parts. Part A is an evaluation of the child's spontaneous speech during a 10- to 15-minute conversation between the child and the assessor. Eight different variables are assessed, and an overview of the child's conversational behaviour is obtained. Part B is an assessment of speech and language skills. A set procedure is used to assess auditory discrimination, interaction between auditory and speech motor capacity, different comprehension functions, vocabulary and word fluency. Some motor tasks are included to elucidate the relationship between speech and non-linguistic fine motor activity. Part C is an interview with the parents. A control group of 40 children was tested. The assessment protocol is now being applied for follow-up examination of children who have needed neonatal intensive care at Uppsala University Hospital, Sweden. PMID- 1300676 TI - Visual impairment of open angle glaucomas at first presentation and after a five to ten year follow-up. AB - Of all patients attended to in a clinic during 1986, 441 had open angle glaucoma diagnosed during 1974-1986 on the basis of either a verified visual field defect, a glaucomatous disc, or a repeated intraocular pressure value of at least 35 mm Hg. At first presentation of recent cases 1984-1986 (N = 128) 65 per cent were more than 70 years old. Capsular glaucomas were twice as common as simple glaucomas (low tension cases included). 62 per cent of capsular but only 26 per cent of simple glaucomas had an initial pressure of 35 mm Hg or more (p < 0.001). One third of both capsular and simple glaucomas had an advanced visual field defect with breakthrough to the periphery in the worse eye already at first presentation. This was more common if the initial pressure was 35 mm Hg or more (p < 0.05). Almost half remained unilateral cases, and the rate of severely impaired visual function in the better eye did not exceed 15 per cent. While generally 30-50 per cent of glaucomatous field defects had progressed in five years, the progression in early detected cases was only three per cent (p < 0.05). Visual field defects with breakthrough to the periphery already at first presentation progressed more often than circumscribed scotomas (p < 0.02). PMID- 1300677 TI - An outbreak of gonadal hypoplasia in a sheep flock: clinical, pathological and endocrinological features, and aetiological studies. AB - In 1984, 31 per cent of 437 ram lambs reared on one property were found to have either bilateral or unilateral testicular hypoplasia. Similar numbers of ram lambs were reared in the next three years and 13, 2 and 0.5 per cent were affected. Severely abnormal testicles typically produced no spermatozoa and presented a 'Sertoli cell only' picture. Sixty-six of 200 ewe lambs born in 1984 were not marked by a harnessed teaser before mating; 12 of these were examined further and eight were found to have bilateral ovarian hypoplasia. The ovaries were very small and contained no oocytes or follicles. Plasma gonadotrophin levels were higher than normal in bilaterally affected rams and ewes but plasma testosterone and inhibin concentrations in rams with bilateral hypoplasia were not significantly different from those in normal rams. A genetic cause of the gonadal hypoplasia was considered unlikely in view of the pattern of occurrence and an examination of the flock pedigrees. No environmental cause was found. Two environmental sources of toxins were considered worthy of further investigation; onion grass (Romulea species) with its leaf spot fungus Helminthosporium biseptatum and the water supply which could have contained high concentrations of arsenic or other toxins during the period when the mothers of the affected lambs were in early pregnancy. PMID- 1300678 TI - Zinc and copper concentrations in the plasma and hair of normal cats. PMID- 1300679 TI - Acute coliform mastitis in dairy cows: endotoxin and biochemical changes in plasma and colony-forming units in milk. PMID- 1300680 TI - Aggressive behaviour in oestrus and dioestrus dairy cows and heifers. PMID- 1300681 TI - Frequency of isolation of Yersinia enterocolitica from livestock in Trinidad. PMID- 1300682 TI - Anaemic beef carcases. PMID- 1300683 TI - Intraoperative use of flunixin meglumine. PMID- 1300684 TI - [The chemosensitizing effect of hyperthermia on normal and tumor cells]. PMID- 1300685 TI - [The risk factors for breast cancer (a prospective controlled study)]. AB - Preliminary results of a prospective study of known risk factors for breast cancer are discussed in the paper. The study included 42,785 females aged 40-64 years who were followed for 2-5 years (mean--3.1 years). Within this period, 146 cases of breast cancer were registered. A significant (p < 0.05) increase in the relative risk (RR) of breast cancer was established for females aged over 50 (50 59 years--RR-1.4; 95% CI--1.0-2.0 and 60-64 years-RR--2.4; 95% CI 1.6-3.7), overweight patients (RR--1.5; 95% CI--1.1-2.1), subjects who developed menopause after the age of 50 (RR--1.6; 95% CI--1.1-2.2) and those with a ten-year or longer history of liver or bile ducts pathologies (RR--1.7; 95% CI--1.1-2.7). The role of certain factors differed significantly in different age groups. At the age of 40-49 years, the RR of breast cancer rose significantly for overweight subjects (RR--2.0; 95% CI--1.2-3.4) and those with liver pathologies (RR--2.5; 95% CI--1.3-4.6), at the age of 50-59-for subjects with late (after the age of 50) menopause (RR--2.0; 95% CI--1.2-3.4) and at the age of 60-64 years-for nulligravidae (RR--2.8; 95% CI--1.1-6.8). PMID- 1300686 TI - [The use of the carbon dioxide laser in the surgical treatment of breast cancer]. AB - The paper discusses peculiarities of breast cancer surgery using high-energy CO2 laser. Advantages of laser scalpel are discussed. CO2 laser was employed in 120 cases of breast surgery including 70 operations for cancer (radical mastectomy and radical resection--35 cases each). Operative blood loss was reduced by half (from 350 to 140 ml). The duration of surgery and wound healing did not increase. Postoperative pain was less severe. The study is in progress. PMID- 1300687 TI - [The treatment of edematous-infiltrative forms of breast cancer by using thermochemo- and thermoradiotherapy]. AB - The study included 157 patients with edematous-infiltrative breast cancer. Thermochemo- and thermoradiotherapy were shown to modify (increase) cancer cell sensitivity to antitumor treatment and thus improve tumor response. PMID- 1300688 TI - [Blood triboluminescence in patients with cancer of the proximal stomach and esophagus]. AB - Total triboluminescence, i.e. optic radiation induced as a result of mechanic activation of venous blood in a TPA-2 triboluminometer, was measured in patients with cancer of the gastric cardia and esophagus, and in healthy subjects. The parameter was assessed in control water samples, too. In the 252-649 nm range, five bands of emission were registered with peaks at 262, 280, 360, 422 and 649 nm subject to variation in certain segments of blood spectrum. Triboluminescence of the venous blood at 280 nm determines for the total triboluminescence registered in the entire spectrum. The triboluminescence of capillary blood at 302 and 418 nm calculated using K coefficient facilitates differentiating between inflammation and cancer. This express test takes less than 1 minute and requires a small blood sample (0.02 ml). The accuracy proved 88%. PMID- 1300689 TI - [The assessment of the hormonal sensitivity of tumors of the large intestine in the adenylate cyclase test]. AB - Sensitivity of 142 human large bowel malignancies to gastroenteropancreatic hormones (VIP, glucagon and pentogastrin) and calcitonin was studied using in vitro adenylate cyclase reaction of tumor. At least 40-55% of the tumors proved hormone sensitive. Heteroresponse (reaction to calcitonin) was most characteristic for colonic tumors whereas weak reaction to VIP and glucagon-for rectal neoplasms. A certain relationship was established between adenylate cyclase reaction to hormone stimulation, on the one hand, and peculiarities of tumor (degree of cell differentiation) and the body (gender), on the other. In patients who survived over 4 years, tumor adenylate cyclase had initially been more sensitive to hormone stimulation than in those who died over that period. It is concluded that tumor adenylate cyclase reaction to hormone stimulation is quite a reliable test for evaluating hormone sensitivity of large bowel tumors and, possibly, for choosing hormonal therapy. PMID- 1300690 TI - [The inhibiting effect of epsilon-aminocaproic acid on the incidence of induced tumors of the esophagus, nervous system and kidneys]. AB - The anticarcinogenic properties of epsilon-aminocaproic acid were studied in two rat models of carcinogenesis. Esophageal tumors were induced by oral instillations of a total dose of 54 mg/kg body weight N-methyl-N benzylnitrosamine whereas tumors of the nervous system and kidney-by transplacental injection of 75 mg/kg body weight N-ethyl-N-nitrosourea. epsilon Aminocaproic acid given at a concentration of 1 milligram drinking water at the post-initiation stage of the carcinogenesis was shown to inhibit the induction of cancer and papilloma of the esophagus, brain glioma, peripheral nerve neurinoma and mesenchymal tumors of the kidney. PMID- 1300691 TI - [An analysis of the visits of breast cancer patients for medical care]. AB - One-hundred and three breast cancer patients were questioned. As few as 35% of them had been regularly checked-up. 52% of patients took medical advice immediately after tumor detection. In 25% of patients, the period between the first examination and referral to a hospital was longer than 1 month whereas 59.2% of patients waited for 1 month to be hospitalized. Inadequate and prolonged examination and malpractice accounted for delayed diagnosis of breast cancer in 64.2%. PMID- 1300692 TI - [Saving the musculus pectoralis minor in radical mastectomy]. AB - Eighty-five patients were surgically treated for postmastectomy edema of the upper extremity. In 20 of them, phlebolysis of the subclavian vein was performed. It was established that the vein was most often compressed by a long stump of the small pectoral muscle. Surgery and subsequent radiation treatment create unfavorable conditions for the muscle leading to its morphologic restructuring. Classic mastectomy after Halsted-Meier is recommended. PMID- 1300693 TI - [The possibilities for improving the quality of life of cancer patients]. AB - The authors emphasize the need for the society and its formations to participate in social rehabilitation of cancer patients. Participation of volunteers from groups of social-psychological support might be a way toward the solution of the problem. PMID- 1300694 TI - [The rehabilitation of breast cancer patients]. AB - Immediate and long-term anatomic, functional, psychologic and social results of radical treatment of breast cancer were assessed in 2 groups of patients who had either undergone or not undergone rehabilitation. The study showed that purposeful rehabilitative treatment and organizational measures assured a decrease in invalidism rate in working age patients from 75 to 43.6% and better quality of life. PMID- 1300695 TI - [The reasons for patients with stomach cancer refusing surgical treatment]. AB - Refusal of treatment was analysed in gastric cancer patients registered in the whole region (12.9%) and in the oncologic dispensary (12.1%). Two hundred and two patients refused treatment, 43 of them agreed to be operated 2 or more months later. Fewer refusals were registered among male and adult patients. The number of refusals increased with age. Reason for refusal were analysed. Explanatory work was carried out and some of them were informed of their diagnosis. Patients were invited for repeated explanation. Low level of medical education of the population, particularly, in the field of oncology was shown to be the main reason to refuse surgery. PMID- 1300696 TI - [Skeletal involvement in lymphogranulomatosis]. PMID- 1300697 TI - [The role of endogenous and exogenous factors in the etiology of skin melanoma]. AB - The results of case-control study of skin melanoma carried out in Moscow are presented. They point to considerable influence of endogenous factors on the relative risk of melanoma. The risk of melanoma is increased by such factors as light color of the skin, presence of freckles and moles. Exposure to UV-radiation raised the risk of melanoma, however, after relevant adjustment for the said factors relative risk was reduced. Consumption of greens and high blood levels of alpha-tocopherol significantly decreased the risk of melanoma. Female users of oral contraceptives had significantly lower risk of skin melanoma. PMID- 1300699 TI - [The hematopoietic characteristics of laryngeal cancer patients undergoing thermoradiosensitization]. AB - Peripheral blood and bone marrow were studied in 46 patients suffering laryngeal cancer. Two schedules of radiotherapy with and without local hyperthermia were used. Complex hematologic study included electron microscopy of the bone marrow. Apart from general hematologic parameters, partial erythro- and granulocytograms of the bone marrow, mitotic index of karyocytes and morphologic anomalies of erythrokaryocytes were studied. Hematologic studies were conducted both before and after a course of radiotherapy. Adverse effect of hyperthermia and radiation therapy on cells of the granulocytic and immunologic component of hemopoiesis was established. PMID- 1300698 TI - [The use of diksafen for curing the neurotoxic reactions of cancer patients undergoing radiation and chemotherapy]. AB - The paper discusses a clinical trial of a newly developed Soviet preparation- dixaphen which was administered to 40 patients who had received radiation and chemotherapy for Hodgkin's disease and tumors at other sites. A single intramuscular injection of 1.0 ml was found to abort emesis in 80-90% and asthenic syndrome--in 60-75%. The drug was well tolerated; it is recommended for treatment of malignant tumors. PMID- 1300700 TI - [Chromosome fragile sites in patients with multiple primary tumors and familial forms of breast cancer]. AB - An analysis was carried out of chromosomal site-fragility in patients with primary multiple tumors and familial breast cancer. A possible correlation is discussed between fragile sites, breakpoints in chromosome rearrangements in cancer patients and the localization of oncogenes mapped in chromosomal regions involved in said rearrangements. PMID- 1300701 TI - [The criteria of the hormonal sensitivity of breast cancer]. AB - The study deals with a complex approach to prognosis of hormone sensitivity in breast cancer patients on the basis of certain biological characteristics of tumor and the host. A number of clinical and morphological parameters were tested in 71 patients suffering breast tumors. The said parameters proved useful in determining hormone sensitivity and were used as a basis for indirect assay of estrogen receptors levels. Levels of estrogen (ER) and progesterone (PR) receptors and tumor sex chromatin (SC) were measured in 46 patients. Indirect determination of ER level should be recommended as an additional criterion for evaluating hormone sensitivity in breast cancer patients considering its findings matching (76-78.2%) those obtained in ER and PR assay by the labeled ligand binding method which uses dextran-covered charcoal. Close correlations (80.4%) and (sensitivity +1) were obtained for ER and PR, on the one hand, and that of sex chromatin, on the other, particularly, in ER+PR(+)-tumors. High concentration of sex chromatin in tumor is one of the most reliable criteria of measuring hormone sensitivity levels in breast cancer patients. PMID- 1300702 TI - [Changes in the cytostatic and cytotoxic activities of the peripheral blood lymphocytes in the surgical treatment of lung cancer patients]. AB - Cytostatic and cytotoxic activity of peripheral blood lymphocytes was studied in 30 cases of lung cancer. Enhanced cytostatic activity of lymphocytes was initially recorded. The level of natural antitumor resistance was maintained by means of neurovegetative inhibition used to prevent surgical stress. PMID- 1300703 TI - [Salivary lysozyme in the screening for stomach cancer]. AB - The study was concerned with measurement of lysozyme activity of saliva in healthy subjects and patients with different pathologies of the stomach including precancer and cancer. It established a considerable decrease in this parameter in cancer and precancer as compared with healthy controls. Assay of saliva lysozyme activity was found to yield more specific and prognostic data than clinical symptoms and examination of the patient. This procedure proved highly valuable in forming groups at risk for stomach cancer, due to providing significant differences in saliva lysozyme activity indices between "healthy subjects- stomach pathology" and "precancer--precancerous changes--stomach cancer" groups. PMID- 1300704 TI - [The oxidative metabolism of the blood neutrophilic granulocytes in precancer and cancer of the stomach]. AB - The results of investigation of blood polymorphonuclear leukocytes oxidative metabolism by nitroblue tetrazolium (NBT) test and luminol-dependent chemiluminescence in patients with gastric precancer and cancer are presented. Chemiluminescence was increased in the patients of both groups as compared with control. Disturbances in oxidative metabolism of neutrophils was detectable by NBT test when functional test was used. PMID- 1300705 TI - [The determination of the concentration of the carcinoembryonic and meconial antigens in the gastric juice of patients with stomach pathology]. AB - Beta-I-MA and CEA concentration in gastric juice was studied in 74 patients with gastric pathology and healthy subjects. Elevated concentrations of beta-I-MA and CEA were found more often in the gastric juice of cancer patients and less often in that of patients without malignant pathology. No significant differences in the concentration of each antigen were found between the "cancer" and "polyp" groups. The combined use of the two test procedures was shown to sufficiently complement the CEA test. The difference in the probability of high concentrations of both antigens in gastric juice in cancer and low ones in other pathologies was highly significant (chi 2 = 15.3, p. 0.00015). PMID- 1300706 TI - [Carcinogenesis induced by the neonatal administration of 5-bromo-2'-deoxyuridine and subsequent exposure to N-nitrosomethylurea in rats]. AB - Shorter life span, higher frequency and multiplicity of tumor, and shorter latency period as compared with intact controls were observed in LIO rats, which were injected, sc, 3.2 mg 5-bromo-2-deoxyuridine (BrdU)--a synthetic analog of thymidine--at days 1, 3, 7 and 21 after birth. Single intravenous injection of 50 mg/kg N-nitrosomethylurea (NMU) into 3 month-old rats treated neonatally with BrdU was followed by a significant increase in the frequency and multiplicity of tumors of certain localizations matched by a shorter latency period as compared with rats pretreated with either BrdU or NMU alone. It is suggested that BrdU induced damage to DNA is sufficient for initiation and development of tumor growth and raising the level of sensitivity to other carcinogenic agents. PMID- 1300707 TI - [The efficacy of polychemotherapy with cisplatin, methotrexate and 5-fluorouracil in inoperable forms of squamous cell cancer of the head and neck area]. AB - The results of treatment of 19 cases of inoperable squamous cell tumors of the head and neck are discussed. The treatment schedule used three drugs: 100 mg/m2 cisplatin at day 1, 25 mg/m2 methotrexate, intravenously, at day 4, and a total of 1000 mg/m2 5-fluorouracil, at days 4-8 of treatment, by continuous 120 hour long infusion. Effect was observed in 15 patients. The treatment was effective in 47.4% (complete regression--in 1 case, morphologically confirmed and partial regression--in 8 cases), stabilization--in 26.3 (5 patients) and further progression--in 26.3% (5 patients). Among the untoward side-effects were nausea, vomiting, anorexia, stomatitis and diarrhea. The toxicity proved tolerable. PMID- 1300708 TI - [The plastic repair of extensive wound defects with vascularized flaps in treating tumors of the skin and soft tissues]. AB - The study was concerned with comparison of the results of application of two procedures of plastic surgery using vascularized flaps for treatment of localized recurrent malignant tumors of the skin, soft tissues of the head, arms, legs and the trunk. According to one procedure (28 patients), large wound defects caused by extensive excision of tumor were treated using tissue flaps and microvascular anastomosis. In the other group of 10 patients, large defects were treated with skin-muscular flaps sitting on a fixed vascular-neural pedicle. But for these two procedures, some cases would not have been operated on at all due to considerable local extension of tumor. PMID- 1300709 TI - [The current status of the problem and the treatment possibilities in disseminated malignant neoplasms of the maxilla]. AB - A study of the results of treatment of 170 patients makes a case for combined electrosurgical resection of the maxilla and local chemotherapy with deposited cytostatic drugs for localized malignant tumors of this site. No recurrences were detected within the first 12 months in 75.4% of patients and 52%--in control. Three-year survival in treated patients and controls was 67 and 48%, respectively. PMID- 1300710 TI - [The clinical significance of bone involvement in patients with primary lymphogranulomatosis]. AB - A retrospective analysis of 2450 case histories of primary Hodgkin's disease established bone lesions incidence at 3.8%. They occurred in cases of general symptoms (6%) rather than otherwise (1.6%). Bone involvement came about chiefly via the blood flow pathway (59%), with several bones being involved in most cases. Dissemination through contact was less frequent 39%), the breast bone or vertebrae being involved relatively more often. Both radiation and polychemotherapy caused local healing effect which would lead to full recovery of bone structure in some cases. Therefore, combined (polychemotherapy + radiation) treatment should be recommended in cases of single lesions whereas treatment for multiple lesions may be limited to medication. PMID- 1300712 TI - [Giant lymphangioma of the breast]. PMID- 1300711 TI - [Esophagogastroduodenoscopy in the diagnosis of benign nonepithelial tumors of the esophagus, stomach and duodenum]. AB - Benign non-epithelial tumors cannot be detected unless endoscopy is used. When coupled with certain other procedures and biopsy it provides means for detection of these tumors as well as identification of their size, site, type of growth and concomitant complications. Single tumors were found in 156 and multiple ones in 4 cases. During the follow-up study, growth of tumor from 1 to 10 mm was observed in 11 cases only. PMID- 1300713 TI - [Rare complications of extensive combined pneumonectomies]. PMID- 1300715 TI - [A combined operation in synchronous multiple primary cancer of the right kidney and sigmoid intestine]. PMID- 1300714 TI - [The use of the contralateral approach for occlusion of the left primary bronchus in bronchial fistulae following pneumonectomy]. PMID- 1300716 TI - [Pancreatic cancer and diabetes mellitus]. PMID- 1300717 TI - [The malignant tumor morbidity of the population of Tyumen Province in 1973-1985 and its prognosis up to 1995]. PMID- 1300718 TI - [The morbidity of pancreatic cancer in the Karakalpak ASSR]. PMID- 1300719 TI - [Sex and pituitary hormone secretion in normal-height and tall adolescents with primary osteogenic sarcoma]. AB - The paper deals with a comparison of basal levels of secretion of total testosterone (T) and estradiol-17 beta (E2), their free and albumin and sex steroid-binding globulin fractions as well as LH, FSH, prolactin and STH in blood serum of 60 normal height and 60 tall healthy adolescents and those with primary osteogenic sarcoma of bones at different stages of puberty. The study established a significantly higher level of testosterone and free androgen index and a lowered concentration of sex-steroid-binding globulin in blood serum of both normal and tall adolescent patients with osteogenic sarcoma at different stages of puberty. No significant differences were found in said indexes of estrogens between sarcoma patients and a specific group chosen for comparison, as far as physical status is concerned. The role of sex steroid hormones and, particularly, that of androgens in the pathogenetical mechanisms of osteogenic sarcoma growth is discussed. PMID- 1300720 TI - [Enzyme and isoenzyme activity in patients with malignant tumors of the oral mucosa]. AB - The activity and isoenzyme profile of lactate dehydrogenase (LDH), alkaline and acid phosphatase were studied in tumors of the tongue, cheek, oral floor, soft palate and palatine tonsils (n = 100), leukoplakia (n = 7) and in the oral mucosa at corresponding sites in healthy subjects (n = 66), to develop tests for early detection, monitoring and prognosis of oral cancer. Levels of alpha-amylase and acid phosphatase were measured in saliva and blood serum of patients with oral cancer and healthy subjects. The activity of LDH and alkaline and acid phosphatase in oral malignancies were 1.5-6 times that in normal mucosa, depending on tumor site. Changes in LDH isoenzyme profile consisted in an increased level of M-subunits (LDH-4 and 5) and a decreased concentration of N subunits (LDH-1 and 2). With regards to acid phosphatase, an increase in the activity of its tartrate-inhibited fraction was observed. An increase in LDH and alkaline phosphatase activity was registered for oral precancer (leukoplakia), too, although it was less pronounced than in cancer. Changes in LDH isoenzyme profile matched those in cancer patients. A significant increase in the activity of alpha-amylase, acid phosphatase and the latter's tartrate-inhibited fraction was registered in saliva of oral cancer patients (86-96%). The credibility of enzyme activity measurement in saliva for evaluation of response and prognosis is discussed. PMID- 1300721 TI - [The positron spectroscopy of neoplasms]. AB - The feasibility of positron spectroscopy of malignant tumors is discussed. Characteristics of the method and its information capacity are briefly discussed. The results of examination of several malignant tumors (cancers of the stomach, rectum, breast and lung and skin malignant melanoma) showed marked differences in the positron spectra of malignant and corresponding normal tissues. PMID- 1300722 TI - [Carcinogenesis induced by the neonatal administration of 5-bromo-2'-deoxyuridine and subsequent exposure to estradiol benzoate in female BALB/c mice]. AB - Female BALB/c mice were given 1 mg 5-bromo-2'-deoxyuridine (BDU) subcutaneously on days 1, 3 and 7 after birth or 5 mg estradiol benzoate (EB) 15 times weekly starting at the age of 3 months or both. Combined application of BDU and EB potentiated the carcinogenic effect of each agent on breast tissue: breast cancer occurred in 80.6% of animals as compared to 15.8, 9.7 and 0% in groups treated with EB or BDU alone and controls, respectively (p < 0.001). Treatment with BDU induced a slightly (but significantly, p < 0.02) higher overall tumor occurrence as well as higher occurrence of primary multiple and malignant tumors and breast cancer as compared to controls. It is suggested that BDU-induced accumulation of DNA errors contributes to initiation of neoplastic changes in the cell and cancer development which is further stimulated by EB. PMID- 1300723 TI - [5-Iodo-2'-deoxyuridine in the assessment of the individual reaction of experimental tumors to irradiation]. AB - C57BL/6 male mice bearing subcutaneously transplanted melanoma B-16 were used to study the applicability of 5-iodine-2'-deoxyuridine labeled with iodine 125 and 131 radionuclides to assess individual tumor response to radiation. The experiments using intact animals and those locally irradiated in the dose of 10 Gy revealed a correlation between excretion of the above-mentioned radioactive labels from tumor area and tumor growth rate for each mouse (correlation coefficient r = 0.93-0.97). 5-Iodine-2'-deoxyuridine excretion rate measurement can be used in express (24-48 hr) tests of individual tumor response to radiation. PMID- 1300724 TI - [Functional research structures and the efficiency of science management in oncology]. AB - The paper discusses feasibility of assessment of the state of the art in research in oncology using information technology and computed functional research structures. This structure allows to identify polar areas of interest, viz. active and passive research. Neutral directions of research serve to exchange information between the two polar areas. This approach allows quantitative evaluation of the importance of the research areas and their interrelationship and offers advantage over expert assessment methods. A critical area of research genetic peculiarities of the malignant cell (tumor genetics)-is identified. The comparative data on the costs involved in analysis of planned research programs using experts and information technology are discussed. PMID- 1300725 TI - [The polychemotherapy of patients with multiple myeloma]. AB - The paper deals with the analysis of the results of chemotherapy of 78 patients with multiple myeloma using various combinations of cytotoxic drugs such as vincristine, cyclophosphamide, sarcolysine (melphalan), rubomycin (adriamycin) and prednisolone (dexamethasone). Reaferon was added in some cases. Response was evaluated according to standard criteria. Survival and response were assessed versus treatment modality and immunochemical type of disease. The most effective chemotherapeutic regimens for multiple myeloma are discussed. It is recommended that remission induction be followed by courses of consolidation treatment and then by maintenance therapy. Reaferon used as a component of complex treatment for multiple myeloma was shown to markedly potentiate the antitumor effect. PMID- 1300726 TI - [The effect of a stay under central highlands conditions on the dynamic indices of the peripheral blood in children receiving treatment for cancer]. AB - The study deals with the effect of rehabilitative treatment given at a medium altitude mountain resort on peripheral blood count in 54 children radically treated for cancer. Hemopoiesis was studied versus type of tumor, treatment modality and follow-up period. Disorders of hemopoiesis were identified in 45 out of 54 children examined. Rehabilitative treatment under said conditions was shown to improve blood count. A statistically significant increase in RBC, hemoglobin and platelet, leukocyte and lymphocyte counts (p < 0.05) was observed. In 42 out of 45 patients with anemia, thrombocytopenia, leuko- and lymphopenia, the indexes returned to normal. PMID- 1300727 TI - [A temporary extracorporeal cavo-caval shunt in the treatment of malignant mediastinal tumors complicated by compression of the superior vena cava]. AB - Gamma-ray teletherapy remains the mainstay in the treatment of mediastinal malignancies complicated by superior vena caval compression. However, patients presenting with severe circulatory disorders die of hypoxia before the effect of radiotherapy sets in. Temporary extracorporeal cava-caval shunt is intended to release blood from the vena cava superior network and then to return it back to the heart by vena cava inferior. The shunt obviates fatal consequences of circulatory disorders and supports the patient until radiotherapy starts to pick up. The method was successfully tested in 7 patients. PMID- 1300728 TI - [A program for the early detection of breast cancer]. PMID- 1300729 TI - [The effect of long-term hepatitis B virus carriage on the late treatment results in stage III breast cancer patients]. PMID- 1300730 TI - [A giant multinodular lipoma of the stomach]. PMID- 1300731 TI - [The immunological aspects of bone marrow transplantation]. PMID- 1300732 TI - [The significance of tumor heterogeneity in metastasis]. PMID- 1300733 TI - [Bladder cancer morbidity in Moscow]. PMID- 1300734 TI - [Skin melanoma: morbidity and mortality in persons under constant observation]. PMID- 1300735 TI - [Lysosomal proteolytic enzymes in the processes of melanoma invasion and metastasis]. AB - Spectrofluorimetry was used to study the activity of lysosomal and membrane binding endopeptidases such as cathepsins B (CB), D (CD) and L (CL) in 72 patients with skin malignant melanoma. Lysosomal endopeptidases were measured separately in the primary tumor, normal skin adjacent to tumor and intact and metastatic lymph nodes. The activity of lysosomal CB in the primary tumor was higher than in the adjacent normal skin. The peak activity of membrane-binding KB was established in metastatic lymph nodes. A significant increase in the activity of lysosomal KB was observed in involved regional lymph nodes as compared to intact ones. The activity of membrane-binding KB in metastatic lymph nodes was 6 times that in metastasis-free ones. A significant increase in the activity of lysosomal KD was established in primary melanoma nodes compared to adjacent normal skin as well as in metastatic lymph nodes compared to intact ones. Preoperative chemo- and radiation therapy was followed by a decrease in lysosomal KB and KL activity in metastatic lymph nodes which, however, did not reach the level established for intact lymph nodes. The pathogenetic role of proteolytic endopeptidases in invasion and dissemination of malignant melanoma is discussed as well as the value of their level measurement for assessing metastatic potential of tumor and prognosis of disease on the basis of tumor site, degree of invasion regional lymph node status. PMID- 1300737 TI - [Tumor markers MCA and CA-125 in the diagnosis and monitoring of breast cancer]. AB - The value of MCA and CA-25 tumor marker assays for diagnosis and treatment of breast cancer was analysed on the basis of measurements made in 320 healthy females and 85 breast cancer patients. A procedure for DK assay with anticipated specificity, sensitivity and reliability is described. MCA measurement was shown to be important for breast cancer diagnosis. The reliability of the latter test for diagnosing progression in the course of follow-up was 91%. Progression of the disease was shown to be associated with an increase in blood CA-125 level in 60% of cases. PMID- 1300736 TI - [Sex and pituitary hormone secretion in adolescents with osteogenic sarcoma and retarded sexual development]. AB - Basal levels of secretion of total testosterone, estradiol-17 beta, their free, albumin-binding and sex steroid-binding globulin (SSBG)--binding fractions, luteinizing hormone, follicle-stimulating hormone, prolactin and somatotropic hormone were measured in blood serum in the following groups of adolescents: (1) healthy, (2) suffering primary osteogenic sarcoma of the bone, (3) osteogenic sarcoma patients with pubertal retardation, and (4) pubertal retardation. A significant increase in total testosterone fraction, free androgen index and a decrease in blood SSBG level were established in osteogenic sarcoma patients as compared to corresponding controls, irrespective of pubertal status. No difference in the above indexes for estrogens was established between osteogenic sarcoma patients and controls in both pubertal status subgroups. The role of sex steroid hormones, particularly, androgens in the pathogenesis of osteogenic sarcoma is discussed. PMID- 1300738 TI - [Estradiol-17beta, sex steroid-binding globulin and the cellular and humoral immunity indices in young women with breast cancer]. AB - Blood serum levels of sex steroid-binding globulin (SSBG), free and SSBG- and albumin-binding fractions of estradiol-17 beta as well as some indexes of cellular and humoral immunity were compared in 25 young female patients with stage 1-3 breast cancer and controls. No significant difference in SSBG and free estradiol-17 beta fraction as well as free estrogen index was established between patients and controls. In the patient group, a direct correlation was established between free estradiol-17 beta fraction level and that of mature T-cells expressing CD3 antigen and between SSBG level, on the one hand, and total level of T-cells (CD7 antigen) and that of T-suppressors (CD8 antigen-containing cytotoxic lymphocytes), on the other. An inverse correlation was established in the same group between SSBG level and that of B-cell markers expressing CD3 and 7 antigens and IgM mu-chain. In the follicular and lutein phases of the menstrual cycle, a difference in the degree of correlation between total estradiol-17 beta level and immunologic indexes was established between breast cancer patients and controls. PMID- 1300739 TI - [The effect of an infection due to the hepatitis B virus on the treatment results in breast cancer patients with bone metastases]. AB - The study deals with the influence of persistent hepatitis B virus infection on immediate and end results of chemotherapy for breast cancer with bony metastases. The infection was shown to be associated with lower complete and partial remission rates, lower 3-year survival rate and higher rate of combination chemotherapy toxic effects such as nausea, vomiting and increased activity of aminotransferases. PMID- 1300740 TI - [The effect of the synthetic immunomodulator thymogen on radiation-induced carcinogenesis in rats]. AB - Five month-old female rats were given a mixture of Sr-90 and Cs-137 in drinking water in the dose of 0.1 and 0.2 microCi/day per animal over 12 months. Some animals received 12 monthly courses of a synthetic immunomodulating dipeptide- thymogen in the dose of 5 micrograms/animal for 5 consecutive days. Radionuclide treated rats showed higher occurrence of tumors on the whole and of breast adenocarcinoma, in particular. Thymogen was shown to inhibit Sr-90- and Cs-137 induced radiation carcinogenesis, namely, a decrease in the total tumor and cancer occurrence was observed. The animals receiving thymogen alone showed longer life span, slower rate of aging and lower overall tumor and cancer occurrence. In this study, the ability of a synthetic peptide immunomodulator- thymogen to inhibit spontaneous and radionuclide-induced carcinogenesis in female rats was first established. PMID- 1300741 TI - [Esophageal tumor induction in monkeys]. AB - The experiment used eight monkeys who had received such esophagotropic carcinogens as ethyl ester of N-nitrososarcosine and methyl-N-benzyl-N nitrosamine. The animals were followed for 4 years. The former agent failed to induce cancer where as 3 monkeys who had received methyl-N-benzyl-N-nitrosamine in the total dose of 600, 625 and 720 mg developed esophageal tumors (papilloma-2 and squamous cell carcinoma-1) at days 527, 725 and 880 after the start of treatment. The biological and histological features of the tumors were close to those of their human counterparts. PMID- 1300742 TI - [Steroid hormone receptors in spontaneous testicular tumors in dogs]. AB - Cytoplasmic receptors to androgens (AR), estrogens (ER), progesterone (PR) and glucocorticoids (GR) were studied in tumors and normal tissue of the testis in dogs. Peculiarities of distribution of receptors were assessed versus age and tumor histology. Benign Leydig cell tumors failed to reveal AR and ER. ER were more often detected in benign Sertoli cell tumors. Malignant seminomas and Sertoli cell tumors were characterized by higher occurrence and levels of AR, GR and PR than their benign counterparts. The results obtained can be used in studies of the activity of newly developed hormonal antitumor drugs against testicular tumors in dogs. PMID- 1300743 TI - [Microsurgical tissue autotransplantation in treating malignant neoplasms of the head and neck]. AB - Results of postoperative reconstruction of surgical defects using microsurgical autotransplants were studied in 72 patients in whom resection of head and neck cancer had been performed. The transplant took root in 64 (87.5%) cases. Musculocutaneous, cutaneous-fascial, cutaneous-osseous and abdominal transplants were used. Microsurgical autotransplantation of tissue complexes assured more rapid rehabilitation and better results of treatment for head and neck cancer. PMID- 1300744 TI - [The problem of the participation of women in a program for the early detection of breast cancer using self-examination]. AB - The USSR/WHO program in Leningrad which included 120000 females aged 40-64 years showed the percentage of breast self-examinees to drop from 82.0 to 55.8, and from 52.3 to 17.9% in those who performed monthly self-examination. This is accounted for by the lack of interest in this problem in the mass media. PMID- 1300745 TI - [The role of the dispensary care of patients with dyshormonal breast diseases in the early detection of cancer]. AB - The results of regular check-ups of 154 patients with dyshormonal pathology of the breast are discussed. 24.2% of patients were cured. Cancer was detected in 11.3%, with 84.4% of tumors being at early stages. It was concluded that patients with dyshormonal pathology be examined every 3 months. PMID- 1300746 TI - [The diagnostic and treatment characteristics of rectal cancer in young persons]. AB - The causes of advancement and results of treatment of 191 patients (aged under 40 years) with rectal cancer seen in 1967-1987 were analysed. The peculiarities of the disease in young age were identified. Timely diagnosis and better results of treatment of rectal cancer in the young can be assured with better educational activities and mandatory rectal examination during oncological check-ups. PMID- 1300747 TI - [The quality of life of patients after cystectomy for cancer]. AB - Quality of life was assessed in 60 cystectomized patients with bladder cancer versus method of urine derivation. Surgery had been ended with formation of "wet" stoma in 39 cases (ureterocutaneostomy--in 30 patients and operation after Bricker--in 9) whereas in 21 cases "dry" stoma had been formed with derivation of the urine into large bowel reservoir assuring controlled voiding. Only as few as 9 (23.1%) "wet" stoma patients retained the pretreatment activity as compared to 100% of those in the other treatment group. One-third of the "wet" stoma patients were unsatisfied with functional results of surgery and preferred formation of the reservoir which assured controlled voiding and allowed freedom from urinal. PMID- 1300748 TI - [A rapidly growing lung hamartoma]. PMID- 1300749 TI - [Spontaneous and irradiation-induced tumor cell death]. PMID- 1300750 TI - [Pharmacological means for eliminating vomiting as a complication of antitumor chemotherapy]. PMID- 1300751 TI - [The humoral immunity indices of patients with malignant skin melanoma using the viral immunomodulator rigvir]. AB - The effect of a viral immunomodulator rigvir on humoral immunity was studied in patients with skin malignant melanoma. Peripheral blood levels of B-lymphocytes, IgA, G and M and circulating immune complexes were assayed and immunoglobulin/B cell ratio (Ig/B) calculated. Preoperative treatment with rigvir brought the indexes of humoral immunity to normal. Response of melanoma patients to rigvir treatment was different from that seen in healthy subjects and was determined by the course of disease. PMID- 1300752 TI - [The cellular immunity indices of patients with malignant melanoma using the viral immunomodulator rigvir]. AB - The effect of rigvir, an immunomodulator of the viral origin, on cell-mediated immunity was studied in patients with skin malignant melanoma. Rosette formation and monoclonal antibody techniques were used to measure blood immunocompetent cell levels in patients with the above pathology, cases of benign skin tumors and healthy subjects. Rigvir was shown to influence natural resistance by raising blood monocyte and large granule-containing lymphocyte levels. It potentiated recruitment of pre-T-lymphocytes and young active T-lymphocytes to the peripheral blood. PMID- 1300753 TI - [The lymphocyte immunological phenotype of young and middle-aged breast cancer patients]. AB - The immunologic phenotype of lymphocytes of young and middle-aged patients with breast cancer was identified using ICO monoclonal antibodies. The parameters were compared to that of healthy subjects of the corresponding age groups. Breast cancer patients of both age groups were shown to have lower T-cell level as compared to donors. Parameters of T-cell-mediated immunity did not differ significantly between the young and middle-aged patients, although the former group tended to have lower level of mature T-lymphocytes. A significant decrease in parameters of B-cell-mediated immunity was observed in young patients as compared to donors whereas in middle-aged patients B-lymphocyte and monocyte levels were 4 times those in donors. B-lymphocyte level in young patients tended to be lower than in middle-aged ones. PMID- 1300754 TI - [The effect of indomethacin and leukinferon on the thromboxane B2 level in the blood plasma of patients with endometrial cancer in the perioperative period]. AB - The paper discusses the effect of indomethacin, leukinferon as well as their combined effect on blood thromboxane B2 (TxB2) level in 40 endometrial cancer patients in the perioperative period. Perioperative treatment with indomethacin was followed by a significant decrease in blood TxB2 level before surgery and in the postoperative period. Treatment with leukinferon exerted similar effect which, however, was less pronounced than that of indomethacin. The effect was most apparent when the two drugs were combined. The influence of indomethacin and leukinferon on metabolism of arachidonic acid in tumor cells and those of the immune system of endometrial cancer patients are discussed as well possible role of eicosanoids in the pathogenetic mechanism of growth and dissemination of reproductive tumors. PMID- 1300755 TI - [The role of monoclonal antibodies to the epithelial membrane antigen in the diagnosis of human tumors]. AB - The paper discusses the possibility of the use of the Soviet-made ICO 25 monoclonal antibodies to membrane antigen of lipid globules of the human milk for differential diagnosis of human tumors. ICO 25 monoclonal antibodies reliably detected the above antigens in normal epithelial and breast cancer cells. However, these antigens cannot be considered strictly specific for breast tissue. They were found in various human epithelial tissues, in the majority of epithelial tumors and lymph node metastases. Staining for ICO 25 monoclonal antibodies was negative in non-epithelial tumors. The above antibodies proved a useful marker for the identification of epithelial origin of primary tumors and their metastases showing unclear histology. They can be used to differentiate between epithelial and non-epithelial malignancies as well as to detect micrometastases and areas of microinvasion. Paraffin-embedded samples can be used for immunohistochemical examination. PMID- 1300756 TI - [Androgen receptors in the cytosol fraction of a spontaneous osteogenic sarcoma in dogs]. AB - The paper discusses results of the assay of androgen receptors in the cytosol fraction of osteogenic sarcoma (primary tumor and metastases) in 17 dogs. In some cases, osteogenic sarcoma and its metastases revealed androgen receptors in a wide range of concentrations (15-340 fmol/mg protein). Metastatic tumors appeared to have the highest receptor levels. Possible role of sex steroid hormones, particularly, androgens in the pathogenesis of osteogenic sarcoma development as well as the use of antiandrogens for the treatment of the tumor are discussed. PMID- 1300757 TI - [Ultrasonic tomography of the mediastinum in the staging of lung cancer]. AB - Results of standard X-ray tomography, computed tomography and ultrasonic tomography (UT) used for detecting mediastinal metastases from lung cancer were compared in 50 patients who were later operated on. UT sensitivity in the diagnosis of paravasal lymph node involvement proved superior to that of X-ray tomography and only slightly yielded to that of computed tomography. As regards bifurcation lymph node assessment, results of the radiation imaging techniques were similar to those obtained by surgery. Ultrasonographic signs of tumor spreading to the mediastinum were observed in cases of stage IIIa-IIIb tumors only. UT assured detection of metastases in normal-sized lymph nodes of the upper mediastinum. Combined application of standard X-ray and ultrasonic tomography of the mediastinum assured better staging of tumor roughly in half the patients. Absence of X-ray signs of mediastinal lymph node enlargement is considered a direct indication for UT. PMID- 1300758 TI - [The intraoperative irradiation of tumors]. AB - Intraoperative irradiation of tumor was performed in 40 patients with cancer of the lung, stomach, breast, bone and soft tissues. It included irradiation of the bed of tumor removed. Fast electron beam was produced by a small betatron (collimator size--5 x 6 cm and 8 x 12 cm) installed in the operating room. Radiation was given to a single or to multiple fields in a single dose of 10-20 Gy to each field. Location of the radioactive source in the operating room proved technically, economically and medically advantageous since it was cheaper, assured a shorter period of the treatment and delivered from patient transportation to a radiotherapy department and ensuing complications. The procedure did not interfere with postoperative period. The efficacy of the treatment modality will be evaluated as soon as sufficient end results have been obtained. PMID- 1300759 TI - [Experience with the use of a low-calorie diet in breast cancer patients to prevent metastasis]. AB - The paper discusses results of three-year follow-up of breast cancer patients keeping to a low-calorie diet after radical mastectomy and chemotherapy. The diet was planned according to age, energy expenditures and body weight and was aimed at a 15% decrease in the total caloricity as compared to corresponding individually-tailored norms for healthy people. This was achieved by reduction in fat (by 30%) and carbohydrates (by 9%). To assure the diet on the domiciliary basis, patients were provided with a table of nutrients for all food products available. Regular examination failed to show any adverse effects of the dietary restrictions on the general status of patients. However, an inhibiting effect of the diet on progression of disease was established, with recurrence being registered in 25% of controls (in 13 out of 52 patients) and only 7% of the study group (in 4 out of 56 cases). PMID- 1300760 TI - [An analysis of the work activities and survival of patients operated on for stomach cancer]. AB - The paper deals with the analysis of dynamics of working activity of 146 radically treated gastric cancer patients examined by the Oncological Commission for Ability Expertise of Novosibirsk in 1984-1988 and then followed for 2-5 years. The percentage of patients returning to work was the highest during the first and third years posttreatment. This was attributed to extension of temporary invalidity period and rehabilitation of group 2 invalids, respectively. Lethality among patients returning to work was 8.2 +/- 2.3% as compared to 62.6 +/- 2.5% in a group of 385 patients who did not work. Labor activity did not adversely influence the clinical course of disease. The unfavorable course was attributed to biological properties of tumor such as low degree of differentiation and infiltrative pattern of growth. PMID- 1300761 TI - [Malignant tumors of the anal canal]. AB - Results of treatment of 381 cases of various malignancies of the anal canal were analysed. The above tumors were classified according to clinical course, histology and stage. Various treatment modalities, peculiarities of early diagnosis, causes of tumor advancement and end results of treatment of cancer of the anal canal are discussed. PMID- 1300762 TI - [The indications for second-look laparotomy in ovarian cancer patients]. AB - Data on 304 patients with ovarian malignancies (mostly epithelial-72.0%) who had undergone second-look surgery were analysed to develop indications and assess the clinical value of the procedure. Second-look operations were performed 10-22 months after primary surgery in the following clinical settings: (1) clinical remission if wash-offs from the Douglas' pouch peritoneum revealed tumor cells or a high blood-CA-125 level was established (8 patients with stage I-II cancer), (2) remission after 6-10 courses of combination chemotherapy (13 patients with stage III-IV tumor), (3) remission following non-radical primary surgery (117 cases), (4) patients with suspected relapse (144), and (5) cases who were not suspicious for relapse but required laparotomy for concomitant surgical pathology such as, for instance, ventral hernia (22). Intra- and postoperative complications were encountered in 29 out of 304 (9.5%) patients and operative lethality rate was 0.9%. It was shown that improvement in noninvasive methods of monitoring allows to limit indications for second-look surgery in stage III cancer. PMID- 1300763 TI - [Data on an evaluation of cancer care and the quality of clinical diagnosis at central district and district hospitals]. PMID- 1300764 TI - [Low-energy lasers in the prevention and treatment of local radiation complications]. PMID- 1300765 TI - [The search for amplification of the ERBB-2 oncogene in human tumors]. AB - The occurrence of ERBB-2 (HER-2/NEU) oncogene amplification was studied in 203 DNA samples obtained from 175 cancer patients. Amplification of ERBB-2 oncogene was established in 14 out of 63 (22%) patients with breast cancer, 1 out of 23 cases of ovarian tumor, 1 out of 19 cases of large bowel cancer and 1 out of 27 patients with cancer of the thyroid. Patients with lung cancer (34), soft tissue sarcoma (6) and malignant melanoma (3) failed to reveal any changes in the above oncogene. A tendency was established for ERBB-2 oncogene amplification to be associated with lymph node involvement in female patients with breast cancer: amplification was observed in 9 out of 28 patients presenting with lymph node metastases and only in 5 out of 29 metastases-free cases. To summarize, ERBB-2 oncogene is fairly often activated in human tumors but a high occurrence of the gene amplification was observed in female patients with breast cancer only. PMID- 1300766 TI - [The reaction of the T-immunity system in patients with malignant skin melanoma and stomach cancer to active nonspecific immunotherapy]. AB - Changes in E-receptor-bearing T-lymphocyte level (total and that of active T lymphocytes) were studied in peripheral blood and resected material obtained from skin malignant melanoma and gastric cancer patients treated with rigvir, an original immunomodulator of the viral origin. Injection of rigvir into peripheral blood was followed by an increase in active T-lymphocyte level and stimulated their migration into tumor. The latter was determined by stage and rate of tumor advancement. PMID- 1300767 TI - [The heterogeneity of the immunological phenotype and of the proliferative characteristics of the lymphoid cells in chronic B-cell lympholeukemia]. AB - Patients with stage III and IV (according to Rai) B-cell chronic lymphocytic leukemia (B-CLL) were shown to differ in the expression of markers such as HLA DR, RFB-1, CD-18, CD-21, activated B-lymphocyte antigen and B-lymphocyte differentiation antigen on mononuclear fraction cells (MFC). Also, differences in the level of MFC proliferation activity during a 72-hour culturing in vitro were established. Some patients with B-CLL showed an increase in lymphocyte proliferation activity in response to treatment with growth factor recombinant interleukin (IL-2) alone and in combination with phytohemagglutinin and phorbol ester. Those changes most often occurred in cases with decreased spontaneous proliferation in culture. PMID- 1300769 TI - [The mitotic regimen of breast cancer in men]. AB - Mitotic regimen of tumor was studied in 75 male and 50 female patients with breast cancer. Mitotic index (9.7 and 14.3%, respectively) and number of pathologic mitoses (28 and 25%) did not differ significantly between the two groups. However, retardation of chromosome movement in meta-, ana- and telophase was 3 times more frequent in males. This suggests that breast carcinoma in males tends to become more aneuploid than in females. The latter reflects the rate of tumor progression. Clinically, breast cancer in males is characterized by rapid growth, early dissemination and resistance to treatment. PMID- 1300768 TI - [The determination of beta-casein gene expression and the assessment of hormonal homeostasis in gynecomastia patients and in breast cancer in men]. AB - beta-Casein genes expression in breast epithelium was studied in male patients with various forms of gynecomastia and cancer. Blood serum levels of pituitary, sex and glucocorticoid hormones were assayed in 29 patients with gynecomastia and 22 cases of breast cancer, and in 25 of them beta-casein genes expression was evaluated additionally. Activation of the above genes was established in the tissues studied. Their level proved to be in a correlation with that of prolactin. PMID- 1300770 TI - [Carcinogenesis induced by the neonatal administration of 5-bromo-2'-deoxyuridine (BUDR) and subsequent exposure to urethane in BALB/c mice]. AB - Male and female BALB/c mice were subcutaneously injected with 1 mg 5-bromo-2' deoxyuridine (BDU) on days 1, 3 and 7 after birth and/or given 0.1 ml 5% urethane solution 5 times every 3 days starting at the age of 3 months. Treatment with BDU alone was followed by retardation of growth, loss of body weight and liver mass but had no significant impact on tumor occurrence. Combined application of BDU and urethane was found to potentiate the effect of the latter agent resulting in an increase in the occurrence and multiplicity of lung adenoma. Male mice treated with the above combination showed a significantly higher occurrence of lung adenocarcinoma and hemoblastoses as compared to the other animal groups. It is suggested that genome instability caused by neonatal BDU treatment potentiates the carcinogenic effect of urethane. PMID- 1300771 TI - [Changes in the adhesion between enterocytes in short-term exposures to blastomogens, retinol acetate and indomethacin]. AB - The study was concerned with the effect of carcinogens and anticarcinogens on the rate of cell loss in the large bowel epithelium of mice. Intestinal carcinogens such as N-methyl-N-nitrosourea and 1.2-dimethylhydrazine were shown to cause a long-lasting decrease in enterocyte loss. Conversely, retinol acetate and indomethacin treatment enhanced cell loss both under normal conditions and in the presence of the carcinogens. The protective effect against N-methyl-N-nitrosourea was more apparent than against 1.2-dimethylhydrazine. The effect was more pronounced in Balb/c mice compared to AKR/J. A close correlation between the protective and the anticarcinogenic effects of the drugs was established. The data obtained suggest that retinol acetate and indomethacin cause reversion of specific early reaction of the large bowel epithelium to carcinogens and are most effective in application in the promotion phase of carcinogens. PMID- 1300772 TI - [An analysis of the connection between the inhibition of NAD biosynthesis and the antitumor activity of drugs]. AB - The study was concerned with a relationship between a decrease in NAD concentration and inhibition of precursor utilization for NAD biosynthesis, on the one hand, and inhibition of Ehrlich ascitic carcinoma growth in response to treatment with embichin, cyclophosphamide, thiophosphamide, adriablastin and methotrexate, on the other. The antitumor effect of drugs was found to be determined by degree of inhibition of precursor utilization for NAD biosynthesis but not by a decrease in NAD level. A relationship between alteration of synchronous induction of NAD and poly (ADP-ribose) biosynthesis rates and reversibility of the antitumor effect of drugs is discussed. PMID- 1300773 TI - [An experimental model of metastatic liver involvement by using Ehrlich's ascitic cancer]. PMID- 1300774 TI - [Skin cancer morbidity among a constant contingent of the population]. AB - A study of skin cancer morbidity in the population followed within 1985-1989 showed skin epithelioma to be the most frequent cancer over the whole period making up 18.2-22.5% of the total number of malignancies. A tendency to an increase in the number of newly diagnosed skin cancers was established (mainly owing to patients in older age groups) with an average growth rate of 9.6%. PMID- 1300775 TI - [Improving the efficiency of detecting central lung cancer at a polyclinic]. AB - Suggestions for restructuring organization of the photoroentgenographic part of the polyclinical diagnostic service are presented. A model of central lung cancer detection was developed which consists of the following basic elements: (1) a program of identification of high risk groups in the ambulatory population, and (2) differentiated standardized X-ray and photoroentgenographic examination in combination with other diagnostic methods. PMID- 1300776 TI - [The role of laparoscopy in assessing the resectability of cancer of the esophagus and proximal stomach]. AB - Laparoscopic findings obtained in patients with cancer of the thoracic part of the esophagus (321) and proximal part of the stomach (383) were analysed. As a result of laparoscopy, unjustified surgery was withheld in 14.9 and 19.3% of cases, respectively. Tumor resectability in the laparoscopy negative group was 92.8 and 84.5% for cancer of the lower and mid-third of the esophagus, respectively, and 76.2% for cancer of the proximal part of the stomach. Laparoscopy yielded false-negative results in 1.9% of cases and failed to be instrumental in diagnosis-in 4.5%. PMID- 1300777 TI - [The prognosis of postoperative complications in patients with cancer of the large intestine]. PMID- 1300778 TI - [A case of surgical treatment in a solitary plasmacytoma of the spine complicated by spinal cord disorders]. PMID- 1300779 TI - [The morphology of kidney tumors induced in rats by iron nitrilotriacetate]. PMID- 1300780 TI - [An erroneous diagnosis of "cancer of the lower lip" and its consequences]. PMID- 1300781 TI - [Selective intra-arterial therapy with cytostatics and radiopharmaceuticals in malignant neoplasms]. PMID- 1300782 TI - [The role of tumor receptor status in choosing adjuvant therapy for breast cancer patients of reproductive age]. AB - Estrogen (ER) and progesterone (PR) receptor levels were assayed in primary tumor samples from 271 premenopausal patients suffering T1,2N1M0 (stage II) breast cancer. Four clinical groups were identified according to steroid receptor levels in which results of adjuvant treatment (chemotherapy or complex treatment) were assessed. ER and PR positivity was associated with longer disease-free and overall survival. Adjuvant hormone therapy proved beneficial in ER+PR+ tumor patients. The latter group was also characterized by a lower relapse rate, particularly, in those aged over 40. It is recommended that: (1) T1,2N1M0 breast cancer patients be given adjuvant chemotherapy whatever tumor receptor status, (2) these patients should not be given adjuvant hormone therapy unless tumor receptor status has been established since prophylactic oophorectomy and subsequent hormone therapy are not justified for operable breast cancer, (3) complex therapy be administered to premenopausal patients aged over 40 years with ER+PR+ tumors only, and (4) PR-positivity be considered a good predictor of hormone sensitivity of cancer. PMID- 1300783 TI - [The assessment of cellular immunity parameters in patients with breast cancer and lymphogranulomatosis during dynamic treatment]. AB - The paper discusses the value of various immunologic techniques for the assessment of status of T-cells and their main subpopulations in patients with breast cancer and Hodgkin's disease in the course of treatment. The immunologic parameters can be used as additional criteria of relapse and grade of response as well as to roughly monitor treatment effect. PMID- 1300784 TI - [The effect of experimental hepatopathy on the nature of the spontaneous metastasis of Lewis lung carcinoma]. AB - The paper deals with the effect of carbon tetrachloride-induced hepatopathy on pattern of spontaneous dissemination of Lewis tumor transplanted to C57B1/6 mice. Antitumor drugs vincristine and rubomycin prevented dissemination to the liver but failed to arrest spreading to the lung. PMID- 1300785 TI - [Latent cancerous pathology of the thyroid]. AB - Postmortem morphologic examination of the thyroid was performed in 122 residents of the Minsk Region, Byelorussian Republic. Various pathology underdiagnosed during life was found in 68%. Fourteen papillary carcinomas were detected in 11 (9.9%) of cases whereas 27 (22.1%) subjects revealed 46 follicular adenomas. Nodular goiter was established in 52.5%, thyroiditis--6.5% and cancer metastases- in 5.7% of cases. The male/female ratio for microcarcinoma was 8:3. All tumor bearing subjects were over 41 years of age. Occurrence of the occult thyroid pathology in different regions of the country can be used to compare potential radiation and other hazards. PMID- 1300787 TI - [The active detection of tumors of the large intestine by using automated screening]. AB - A system for automated screening for early detection of proctologic pathologies is described. Questionnaire-based data, formation of high risk groups using a computer and results of examination of 1660 office and professional workers of an industrial enterprise according to a given program are discussed. After filled questionnaires had been processed using a computer, 134 (8%) subjects were selected to group 1, 454 (27%) subjects-to group 2, 383 (23%) subjects-group 3 and 689 (42%) subjects-to group 4. Proctologic pathologies were detected in all persons of group 1, 83% of those in group 2 and in 30% cases of group 3. Asymptomatic proctologic pathology was established in 630 (37.8%) screenees of whom 10 revealed large bowel tumors, 5 early cancers included, whereas 49-large bowel polyps. PMID- 1300786 TI - [The combined magnetoradiotherapy of breast cancer]. AB - Preoperative magnetoradiation therapy of stage II-III breast cancer patients was followed by pronounced regression of tumor and axillary lymph node metastases in all cases. The treatment modality had been previously substantiated by establishing the optimal sequence and time intervals for magnetic and radiation fields. Complete regression of primary tumor and metastases verified by histologic and cytologic examination of surgical and biopsy material was observed in 20%. The best results were obtained for edematous-infiltrative form of cancer. In the control group (radiation alone), regression of tumor was only slight, nor did lymph node metastases regress. Magnetoradiation therapy did not involve either immediate or delayed adverse side-effects. PMID- 1300788 TI - [The use of extraperitoneal colorectal anastomoses in complicated cancer of the rectum and sigmoid]. AB - The paper deals with the issue of primary restoration of intestinal continuity in complicated colorectal cancer using extraperitoneal colorectal anastomoses. The study is based on the experience of treatment of 35 cases of complicated colorectal cancer. It was concluded that, to assure primary restoration of intestinal continuity, the risk of surgery must be weighed with respect to extent of disease, and adequate anesthesiologic and postoperative intensive care is required. The procedure should be performed at a specialized surgical institution. PMID- 1300789 TI - [The work of the Kemerovo Interregional Department of Pediatric Oncology]. AB - The Department of Pediatric Oncology, Kemerovo, has operated as an interregional center since 1976. Cancer morbidity and epidemiology in children in the Kuzbass region have been studied. Complex treatment yielded good results: 2-20-year survival rate is 89.6% for Hodgkin's disease, nephroblastoma--75.4% and neuroblastoma--38.5%. The improvement in the results obtained makes the case for establishing a department for patient rehabilitation. To function properly, the center needs more beds. It must be in a position to carry out organizational and educational activities in catchment areas. The status of the center must be supported by official documents. PMID- 1300790 TI - [The clinical manifestation of malignant neoplasms of the small intestine]. AB - The paper discusses the findings of a retrospective analysis of 8294 case histories of intestinal tumors. Tumors of the small intestine were detected in 140 cases (1.6%). Five clinical forms of manifestations of tumors of the small intestine were identified on the basis of case histories and clinical course. PMID- 1300791 TI - [The attitude of medical institute students to cancer patients]. AB - One hundred and twenty-eight fourth-year and 106 fifth-year medical students were questioned to evaluate their attitude to cancer patients. After taking a course in oncology, 11.3% of students considered cancer "contagious" or "likely to be contagious" and half the students considered cancer prevention "ineffective" or "likely to be ineffective". They distance themselves from cancer patients in family relations and their relations were closer in every day life and with friends. PMID- 1300792 TI - [Aggressive recurrent fibromatosis]. PMID- 1300793 TI - [A case of the successful use of nitrosomethylurea in lymphosarcoma complicated by prolonged massive chylothorax]. PMID- 1300794 TI - [An unusual combination of multiple primary benign and malignant tumors]. PMID- 1300795 TI - [A teaching program for the diagnosis of lung cancer and mediastinal tumors for personal computers]. PMID- 1300796 TI - [The psychological aspects of oncology]. PMID- 1300797 TI - [A method for the guided puncture of tumors of the abdominal cavity under ultrasonic control in children of younger age groups]. PMID- 1300798 TI - [The taking of sex hormone preparations and the risk of developing breast cancer]. PMID- 1300799 TI - [The laryngeal cancer morbidity of the population of Kyrgyzstan]. PMID- 1300800 TI - [Thymus endocrine function and the immune system indices of cancer patients after neutron and gamma therapy]. AB - Patients with head and neck and locomotor system tumors received neutron therapy in the total doses of 4-8 and 12-14 Gy which was followed by a pronounced dose dependent decrease in the serum thymus factor and total blood-lymphocyte levels. The latter changes were predominantly due to a decrease in the non-T-non-B cell concentration. Following the treatment, a rise in the level of circulating immune complexes and those of IgA and IgG was observed. Changes in the immune system proved less apparent in patients with locomotor system cancer who had been given 20 Gy of gamma-ray radiation. PMID- 1300801 TI - [Adenogenous cancer of the esophagus]. AB - Bioptates and resected material from patients treated for cancer of the esophagus at the Kazakh Research Institute of Oncology in 1980-1989 were analysed. Adenogenic tumors made up 6.0% of the 1671 cases of esophageal cancer studied. A gradual increase in the percentage of adenogenic cancers was established (P < 0.05). A group of 100 cases of adenogenic cancers was examined in detail. Adenocarcinoma made up 5.3%, adenosquamous cancer--0.5 and adenocystic cancer- 0.2%. Adenogenic cancers most often occurred in the lower thoracic part of the organ. Poorly differentiated adenocarcinoma predominated (56.8%), with a tendency to an increase in the tumor occurrence in the upper and mid-thoracic parts. The enhanced morbidity from adenogenic cancers is attributed to a high occurrence of esophagitis in the majority of regions of Kazakhstan. PMID- 1300802 TI - [The characteristics of eicosanoid synthesis in osteogenic sarcoma in children at puberty]. AB - Levels of prostaglandin E (PGE), prostaglandin F2 alpha, prostacyclin A2, thromboxan B2 and leucotriene B4 assayed radioimmunologically were compared in 42 samples of osteogenic sarcoma and 22 samples of benign tumors and tumor-like lesions from children at the pubertal period. In osteogenic sarcoma samples, PGE and prostaglandin F2 alpha levels were higher than those of thromboxan B2, prostacyclin A2 and leucotriene B4. Osteogenic sarcoma revealed higher levels of the eicosanoids as compared to benign tumors and tumor-like lesions of the bone. An inverse correlation was established between PGE level and time of dissemination of osteogenic sarcoma. The role of eicosanoids in the pathogenesis of growth and dissemination of osteogenic sarcoma is discussed. The use of non steroid anti-inflammatory drugs in complex treatment of osteogenic sarcoma of children at the pubertal period is suggested. PMID- 1300803 TI - [Neoadjuvant chemotherapy in combined treatment of breast cancer]. AB - The paper deals with results of complex treatment of 387 patients with stage III breast cancer assigned to either neoadjuvant chemotherapy and preoperative radiotherapy or radiation alone. A study of immediate and end results showed combination of the two modalities to be more effective than each method alone in terms of degree of regression of primary tumor and, particularly, lymph node metastases and duration of recurrence-free period. PMID- 1300804 TI - [The possible carcinogenic properties of riboxin (inosie F)]. AB - Long-term treatment of rats and mice with riboxyn failed to reveal the carcinogenic effect of the drug. Chronic experiments showed the drug to improve resistance of the animals to intercurrent infections. PMID- 1300805 TI - [A comparative study of the individual characteristics of the excretion of metabolites of benzo(a)pyrene and its carcinogenic effect in rats]. AB - Nineteen outbred LIO rats received a single intraperitoneal injection of 200 mg/kg benzo(a)pyrene (BP) in sunflower oil. Levels of excretion of a BP activation product 7.8-BP-dihydrodiol and deactivation product 3-hydroxy-BP showed significant individual variations. Half the animals developed intraperitoneal sarcoma at various stages of the experiment. A direct correlation between urine 7.8-BP-dihydrodiol excretion level and tumor latency was established. The value of metabolite excretion level monitoring for making individual prognosis of BP carcinogenic effect is discussed. PMID- 1300806 TI - [The anticarcinogenic effects of fumaric acid on models of carcinogenesis in the esophagus, nervous system and kidney]. AB - Anticarcinogenic effects of the fumaric acid was studied in two rat models of carcinogenesis. Tumors of the esophagus, forestomach, tongue and throat were induced by peroral instillation of 35 mg/kg body weight N-methyl-N benzylnitrosamine, and neurogenic and renal ones--by transplacental injection of 75 mg/kg body weight N-ethyl-N-nitrosourea. The fumaric acid given in drinking water in the dose of 1 g/l at the postinitiation stage of the carcinogenesis was shown to inhibit the development of esophageal papilloma, brain glioma and mesenchymal tumors of the kidney. PMID- 1300808 TI - [Approaches to the study of the incidence of benign tumors in the pediatric population]. AB - Occurrence of benign tumors in large pediatric population have never been studied. Basing on the data on the pediatric population of Khabarovsk, the authors developed a method of improved analysis of benign tumor morbidity. The method suggests the use of case histories as well as medical check-up data. Mathematical modelling was employed to compare primary incidence and occurrence indexes. The improved mean incidence of benign tumors in children for 1985-1989 was 66.8 cases and improved occurrence--174.2 per 10,000 children. The values are by the order of magnitude higher than those reported by hospitals. PMID- 1300807 TI - [The individual characteristics of the activity of the DNA-repair enzyme O(6) alkylguanine-DNA alkyltransferase in the stomach of monkeys exposed to the gastric carcinogen N-ethyl-N1-nitro-N-nitrosoguanidine]. AB - Variations in the activity of a DNA repair enzyme 0(6)-alkylgianine-DNA alkyltransferase (AGT) were studied in gastric mucosa samples obtained from 15 M. fascicularis monkeys chronically exposed to a gastrocarcinogen N-ethyl-N'-nitro-N nitrosoguanidine. Marked interindividual difference in the enzyme activity before and in the course of the exposure was observed. The value of AGT activity assay to predict individual susceptibility to alkylating carcinogens is discussed. PMID- 1300809 TI - [The role of the day hospital in providing diagnostic and therapeutic care for children with malignant tumors]. AB - The day hospital proved effective for diagnosis and treatment of pediatric cancer. It is more cost-effective and less emotionally traumatic for patients than the usual hospital. PMID- 1300810 TI - [The use of low-energy lasers for preventing and treating postoperative and radiation-induced complications in patients with head and neck tumors]. AB - The efficacy of low-energy helium-neon and copper vapor lasers for prevention and treatment of postoperative and irradiation complications was assessed in 195 patients with locally advanced tumors of the head and neck. The control group included 118 patients. Intravenous laser irradiation of the blood was associated with a higher percentage of wound healing by first intention and better course of the postoperative period. Laser treatment of skin irradiation fields was shown to improve skin tolerance to the neutron beam. The study failed to establish tumor growth stimulation by the laser irradiation in terms of recurrence and metastasis development. The data obtained showed low-energy laser irradiation to offer promise for prevention and treatment of postoperative and irradiation complications. PMID- 1300811 TI - [The practical use of the determination of relative 32P accumulation in the tumor in breast cancer]. AB - The level of relative accumulation of a 32P radionuclide was measured in 180 tumor samples obtained from 148 patients with stage I--IV breast cancer. Mean initial relative accumulation level (IRAL) was 1477 +/- 174% whereas that following effective conservative treatment (posttreatment) (PRAL)--486 +/- 81% (P < 0.01). The prognostic value of IRAL was established: in a group of stage III breast cancer, those with a high IRAL survived 2 years with no evidence of disease in 55.1 +/- 12.1% whereas those with a low IRAL--in 94.1 +/- 5.7% (P < 0.02). In patients undergoing conservative treatment, low PRAL proved predictive of complete response while high PRAL--of tumor progression. In patients with stage III breast cancer who had responded to preoperative treatment and had had a low PRAL, two-year locoregional recurrence rate was only 13% as compared to 68% in a similar group of patients with high PRAL (P < 0.02). PMID- 1300812 TI - [Tracheobronchomegaly combined with tracheal cancer and pulmonary tuberculosis]. PMID- 1300813 TI - [Lymphosarcoma of the stomach in children]. PMID- 1300814 TI - [Stomach cancer in persons younger than 40]. PMID- 1300815 TI - [The role of N-nitroso compounds and their precursors in the etiology of human tumors]. PMID- 1300816 TI - [Breast cancer in men]. PMID- 1300817 TI - [The epidemiology of malignant tumors in the printing industry]. PMID- 1300818 TI - [The dynamics of esophageal cancer morbidity in Kazakhstan]. PMID- 1300819 TI - [Increased risk factors for the occurrence of bladder cancer]. AB - Risk factors of bladder cancer development were studied in a population-based case-control epidemiological study performed in Moscow. Relative risk (RR) indexes appeared to be increased in smokers (4.2) and ex-smokers (3.5) with statistically significant trends for two most important factors such as duration of smoking and duration of withdrawal. A pronounced although insignificant increase in the RR indexes was established for drivers (3.0) and a slight insignificant rise-for gas arc welding operators (1.5). The indexes were increased in subjects with a family history of cancer. The relative risk of cancer was significantly lower in beta-carotene consumers. A preventive effect of polyunsaturated fatty acids and oil and margarine used for frying was established. Risk of bladder cancer tended to increase with a rise in dietary protein. A dose-effect type inhibition of advancement of the disease by vitamin C was observed. PMID- 1300820 TI - [The inhibiting effect of phytoadaptogenic preparations from bioginseng, Eleutherococcus senticosus and Rhaponticum carthamoides on the development of nervous system tumors in rats induced by N-nitrosoethylurea]. AB - The study was concerned with the inhibitory effect of officinal preparations of phytoadaptogenic drugs such as bioginseng and Eleutherococcus senticosus and Rhaponticum carthamoides root extracts on the carcinogenesis induced by transplacental administration of N-nitrosoethylurea. The phytodrugs were given orally over a year. The administration of the drugs was followed by longer survival of the rats and lower occurrence and/or multiplicity of tumors (mainly those of the central nervous system). The drugs were placed in the order of decreasing anticarcinogenic activity as follows: bioginseng, Rhaponticum carthamoides extract and Eleutherococcus senticosus extract. PMID- 1300821 TI - [An experimental study of the tumor affinity of gallium-67-labelled sphingomyelin liposomes]. AB - The level of accumulation of sphingomyelin liposomes with 67-Ga-labelled aqueous phase in tumor tissue proved higher than that of the vesicles with labelled lipid phase. Presence of cholesterol in sphingomyelin liposome membranes failed to influence liposome accumulation in tumor tissue. Neutral sphingomyelin vesicles with 67-Ga-labelled aqueous phase offer promise in scintigraphic imaging of tumors. PMID- 1300822 TI - [The effect of the time of methotrexate administration over 24 hours on the antitumor activity of the preparation, its concentration in the blood and in the tumor in Pliss' lymphosarcoma in rats]. AB - A mismatch between a circadian rhythm of blood-methotrexate level and that of the drug concentration in rat transplanted lymphosarcoma tissue was established. The drug proved 3 times more effective when given at the time of the day when its concentration in tumor tissue was likely to be the highest. PMID- 1300823 TI - [The growth and metastatic characteristics of Lewis lung carcinoma during reproductive dysfunction in male C57BL/6 mice]. AB - Results of a study of the pattern of spontaneous dissemination of Lewis lung carcinoma in male mice with reproductive system dysfunction showed that removal of the gonads followed by substitution treatment with testosterone failed to influence tumor metastatic potential. The data suggested that the androgen lacked a modulating effect on growth and dissemination of Lewis lung carcinoma. PMID- 1300824 TI - [The possibilities for organ-preserving treatment in retinoblastoma in children]. AB - One-hundred pediatric patients with uni- and bilateral retinoblastoma (140 tumors on the whole) received a combination of radio- and chemotherapy. Radiation was delivered by gamma-ray units and an electron accelerator. The single and total focal doses used were 1.5-2.0 Gy and 40-55 Gy, respectively, depending on tumor stage. Simultaneously, chemotherapy with vincristine, cyclophosphamide and adriamycin were given intravenously in standard doses. As a result, 85 out of 95 (89.5%) children including 43 cases of bilateral tumor are alive. Partial response or no change were registered in 72 tumors (51.4%). Progression was observed in 28 tumors (20%) at the average of 6-8 months following the start of treatment. Forty tumors (28.6%) responded completely, with remissions lasting for a follow-up period of 2-6 years. Not a single case of organ-sparing surgery developed distant metastases. To summarize, a combined treatment modality for retinoblastoma according to TNM stage was developed and indications for organ sparing surgery outlined. The standard treatment modality for bilateral retinoblastoma was revised. PMID- 1300825 TI - [The forming of uniform groups of patients with peripheral lung cancer: the methodological bases and clinical importance]. AB - In a group of 268 cases of operable peripheral lung cancer, subgroups homogeneous for major prognostic factors were formed which differed in end results of radical treatment, rate of dissemination and response to additional radiotherapy. The method allows to choose optimal diagnostic and therapeutic options for an individual patient. PMID- 1300826 TI - [An assessment of the efficacy of preoperative radio- and thermoradiotherapy in treating rectal cancer]. AB - Immediate results of combined and surgical treatment of 415 patients with stage III rectal cancer were analysed. Combined treatment including intensive preoperative irradiation and preoperative thermoradiotherapy was not associated with higher postoperative lethality as compared to surgery alone, the indexes being 1.9 +/- 0.9%, 3.8 +/- 2.6% and 2.7 +/- 1.3%. Pyoinflammatory complications developed in 40.7 +/- 3.3% and 45.6 +/- 6.8% of cases in the two combined treatment groups, respectively, and in 33.2 +/- 3.8% in the control group. In patients subjected to preoperative irradiation in combination with microwave hyperthermia, no increase in the occurrence of pyoinflammatory complications was observed, but surgical wounds took longer to heal. The rate of complications following sphincter-sparing procedures, whether used alone or in combination treatment, was similar. It is concluded that the use of combined modality treatment should not bar sphincter-sparing surgery. PMID- 1300827 TI - [Errors in the diagnosis of tumors of the retroperitoneal space of nonorganic origin]. AB - The analysis of case histories of 152 patients with non-visceral tumors of the retroperitoneal space established misdiagnosis of tumor in 45.7%. Some patients (38.1%) presented with tumor, swelling and/or severe pain in the ipsilateral leg. Tumor proved inoperable in 50.4%. Diagnosis of tumor is complicated mainly by the diversity of patterns and peculiarities of clinical course. Also, lack of knowledge about the pathology and unawareness of cancer may account for misdiagnosis by general practitioners. PMID- 1300828 TI - [Cystectomy in bladder cancer patients]. AB - Within the last 12 years, 125 patients have been subjected to cystectomy which makes up 18.0% of the total of 691 surgical patients. The majority of patients were at T3 (64) or T2 stage (50) whereas T1 and T4 tumors were observed in 8 and 3 cases, respectively. Four patterns of urine derivation were used after cystectomy: ureterosigmoid anastomosis--in 8 patients, one-stage cystectomy with ileocystoplasty--23, double-stage cystectomy with ileocystoplasty--48 and ureterocutaneostomy--in 46 cases. Ileocystoplasty proved the best procedure for urine derivation. Depending on patient condition, it may follow cystectomy immediately or be carried out in 2 stages: cystectomy with ureterocutaneostomy followed by ileocystoplasty 2-4 months after the first operation. PMID- 1300829 TI - [The fate of bladder cancer patients who refused radical treatment]. AB - Survival of 117 operable male patients who had refused treatment was compared to that of 267 male patients who had undergone radical therapy. It was shown that treatment did not influence five-year survival of patients with T cancer. The same tendency was observed for T4 tumors. Radical treatment was associated with a significantly longer survival in T2-3 cancer patients. In the T1-2 tumor group, mean survival following diagnosis was affected by patient age whereas the relationship was far less apparent in cases of T3-4 cancer. PMID- 1300830 TI - [The protective action of sodium thiosulfate in cytogenetic experiments with 1,3 dimethyl-1-nitrosourea on rats]. PMID- 1300831 TI - [New Ventures. "Strong members can change the profession". Interview by Jan Thomasson]. PMID- 1300832 TI - [New Ventures. We flex freely with Ulf and Laban in the medical clinic. Interview by Elisabet Forslind]. PMID- 1300833 TI - [Ragnhild teaches self care in the pharmacy. Interview by Jan Thomasson]. PMID- 1300834 TI - [From a big city to small Ven--Inger dares take a leap. Interview by Anders Olsson]. PMID- 1300835 TI - [New Ventures. Write down what you can, nurse!]. PMID- 1300836 TI - [New Ventures. Career can break apart solidarity. Interview by Birgitta Dalenstam]. PMID- 1300838 TI - [New Ventures. Work exchange gathers everybody in the Laboratory in Karlskrona]. PMID- 1300837 TI - [New Ventures. Education teaches us not to venture out. Interview by Maria Ejd]. PMID- 1300839 TI - [4 out of 5 ideas are don't take place--"desire to take part in meeting is overwhelmingly great". Interview by Christina Mork]. PMID- 1300840 TI - [New Ventures. Nurses a part of the health care team--and a physician at the head. Interview by Kaj Nyman]. PMID- 1300841 TI - [Soon emancipated members aim for SFSTF venture]. PMID- 1300842 TI - [New Ventures. Environment's support important when one ventures out. Interview by Carina Roxstrom]. PMID- 1300843 TI - [Here is New Ventures!]. PMID- 1300844 TI - [It means we must come to terms with our internal obstacles. Interview by Kaj Nyman]. PMID- 1300845 TI - [Nurses in Kalmar on New Ventures: "It has helped us to improve our work"]. PMID- 1300846 TI - [Prevalence of gallbladder lithiasis in a Uruguayan population]. AB - Ultrasound examinations were carried out in 693 volunteers from the health care personnel of the Hospital de Clinicas of Montevideo, with the aim of studying the prevalence of gallbladder gallstones in Uruguay, the proportion of symptomatic and asymptomatic people and its association to some definite risk factors. The prevalence found was 10.4%, which, according to the sample's size, is representative of the general population with a confidence of 99%. Sixty five per cent of gallstones carriers were asymptomatic. A statistically significant association with the following factors was found: people between 31 and 50 years old, slight obesity, and, for women, to have children. A marked tendency with the following factors was found, though it was not statistically significant: female sex, and a familiar history of mother carrying gallstones. Considering all these factors as a whole, the probability of having gallstones reached 19%. Results are discussed and compared with those of foreign publications. It is concluded that uruguayan people with more possibilities of having gallstones are: women between 31 and 50 years old, obese, with children, and whose mother has or had the same disease. PMID- 1300847 TI - [Achalasia and esophageal cancer]. AB - During the period included between January 1970 and December 1990, we studied 242 patients with manometric and radiological diagnosis of esophageal achalasia. Eight of these patients (3.3%) developed during the evolution of their disease an esophageal carcinoma. Eight cases showed histologic type of epidermoid carcinoma: 3 differentiated, 3 semi-differentiated and 2 anaplastic. Therapy for achalasia was: one patient, Heller myotomy, 4 patients, dilatations with bougies in numerous opportunities, and the other two patients receive no treatment for achalasia. Two patients reported tracheobronchial fistulas as complication of carcinoma. Treatment received for carcinoma included: three patients, radiotherapy (4000 rads); one patient, chemotherapy; one patient, chemotherapy and radiotherapy, one resection surgery and two patients feeding gastrostomy. All of the eight patients died within the year of diagnosis of epidermoid carcinoma. PMID- 1300848 TI - Clonidine treatment of acute pancreatitis: report of five cases. AB - We report five consecutive cases of patients with acute pancreatitis resistant to conventional treatment who improved dramatically with clonidine. All patients showed greatly elevated noradrenaline, adrenaline and cortisol plasma levels (physiological indicators of stress) which fell abruptly upon initiation of clonidine therapy. The clonidine test performed in the patients showed a hyper response in all, a reaction consistent with uncoping stress situation. Therefore, we postulate that stress might play a role in the pathogenesis of these patients pancreatic inflammatory disease. PMID- 1300849 TI - [Adenoacanthoma of the upper esophagus. Report of a case]. AB - We report a 72 year-old woman, with adenoacanthoma of the upper esophagus who was admitted in Hospital Israelita "EZRAH" in April of 1991. We performed a review of the literature on this rare tumour, that is the reason of presenting this case. PMID- 1300850 TI - [Ascariasis of the gallbladder. Report of 2 cases and review of the literature]. AB - Two patients who complained of a clinical picture compatible with cholelithiasis; and in whom the diagnosis of ascariasis of the gallbladder was made sonographically, are reported. In the first patient, cholecystectomy was curative and corroborated the presence of the roundworm. In the second patient, piperazine citrate was given. A second sonogram performed after therapy showed no roundworm within the gallbladder; and the patient remains asymptomatic until now. The usefulness of ultrasonography in the diagnosis of gallbladder ascariasis, and during surveillance in those patients who are managed with medical therapy only, is emphasized. PMID- 1300851 TI - [Diet and colorectal cancer]. PMID- 1300852 TI - [Treatment with extracorporeal shockwave (ESWL) in lithiasis of the common bile duct]. AB - During 2 years (1988-1990) 373 patients were studied by ERCP in order to establish the etiology of cholestasis. Biliary duct stones were found in 190. Thirty-nine were treated surgically and 151 by endoscopic sphincterotomy and different extraction techniques. In 12 patients of the last group (9 women, 3 men, mean age 71 years, 9 had undergone cholecystectomy and 3 has their gallbladders in situ), ESWL was used as additional treatment to fragment the stones that could not be removed with the Dormia basket or with mechanical lithotripsy. Four patients had only one stone in their biliary ducts, 5 had two, and 3 had more than two stones. The size of the stones was greater than 2.5 cm. in 11 patients, only 1 patient had a 1 cm. diameter stone. In each session between 1200 and 5000 shock waves were administered (mean 1400). In 8 patients (66%), the fragmentation was successful to achieve their spontaneous passage or their extraction with a basket. In 4 who received only one session of ESWL, the procedure failed to break the stones. Side effects were observed in 3 cases: mild haemobilia in 1, skin petechiae and pain in 2 patients. No complications were observed in the long term follow-up. We conclude that ESWL is useful in the treatment of biliary duct stones which cannot be extracted through sphincterotomy with a basket or mechanical lithotripsy. PMID- 1300853 TI - [Fluidity of hepatic microsomal membrane and its relation with aging]. AB - The effect of aging on hepatic microsomal membrane phospholipid composition was studied composition was studied in both young (2 months) and mature (6 months) Wistar rats. When total microsomal phospholipid content was analysed the aged group showed a significant increment (73%). Microsomal phospholipid pattern also showed a different behavior between both groups, with a significative increase in phosphatidylcholine (62%), phosphatidylserine (124%), phosphatidylinositol (31%) and sphingomyelin (10%) and appearance of phosphatidylethanolamine and phosphatidylglycerol in the six-month group. A higher microsomal membrane fluidity in the aged animals was revealed by the increase in PC/EM index (47%). This increment jin fluidity during aging process may reflect an adaptative response resulting in changes on the enzyme activities responsible for drug and carcinogen metabolism. PMID- 1300854 TI - Fecal alpha 1-antitrypsin clearance in the differential diagnosis of steatorrhea. AB - We reviewed the fecal fat excretion and alpha 1-antitrypsin clearance results of 160 patients with steatorrhea in whom a final diagnosis was obtained, based on history, physical examination, and radiological, functional and morphological tests. Twenty-two patients had pancreatic diseases and 138 had steatorrhea due to gastrointestinal diseases. alpha 1-antitrypsin clearance was invariably normal in chronic pancreatitis, but there was only a 23 to 50% of correct etiological classification when the combination of steatorrhea and normal alpha 1-antitrypsin clearance was present. However, none of our patients diagnosed of chronic pancreatitis had abnormal alpha 1-antitrypsin clearance. The combination of steatorrhea and normal clearance of alpha 1-antitrypsin was a modest clue for diagnosis of pancreatic malabsorption. PMID- 1300855 TI - Prostaglandin synthetase inhibitor treatment and the regulatory role of prostaglandins on organ perfusion. AB - Prostaglandin synthetase inhibitors (PGIs) are increasingly used in anesthetic practice and postoperative care. The influence of these agents on the hemodynamics and organ perfusion control remains largely unknown. This review attempts to assess the role of endogenous prostaglandins on the regulation of the microcirculation in different organs and to identify disease states in which PGIs may have deleterious effects. Prostanoids participate to the regulation of blood pressure as vascular tone is subject to the continuous relaxing influence from endogenous vasodilating prostaglandins or related substances. Prostacyclin (PGI2), probably the most important physiologic modulator, decreases blood pressure with concomitant increase in cardiac output and reduction of systemic vascular resistance related to the peripheral vasodilation. Also splanchnic, pulmonary and coronary vasodilation are observed with increased blood flows in the mesenteric, renal and coronary beds. These changes in regional blood flows have been linked to the inhibition by PGI2 of the vasoconstrictor response to sympathetic stimulation and pressor hormones (noradrenaline, angiotensin II). Other prostaglandins exert their effects by inhibiting the release of noradrenaline at the noradrenergic terminals of the sympathetic system. PGIs appear to provide hemodynamic stability during intra-abdominal surgery. Data suggest that the underlying mechanism is an increase in systemic vascular resistance. PGIs have beneficial effects in hemorrhagic shock models in animals and humans but can also exacerbate hemodynamic and metabolic derangements in acute hypovolemic hypotension. In animal models these agents reduce regional blood flow in the ischemic myocardium and may increase infarct size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300857 TI - Propofol to provide sedation after coronary artery bypass surgery. A comparison of two fixed rate infusion regimens. AB - Propofol (2,6, di-isopropylphenol) was given by continuous intravenous infusion to provide sedation following coronary artery bypass surgery. The need for additional sedation, analgesia and hypotensive agents was assessed at two propofol infusion rates (10 or 25 micrograms/kg/min). Both rates provided clinically satisfactory conditions. There were no differences in the requirements for analgesia or vasodilators between the groups. The higher infusion rate of 25 micrograms/kg/min was associated with a lower requirement for additional sedation but a more frequent need to stop the infusion temporarily to prevent hypotension. PMID- 1300856 TI - Epidural bupivacaine versus epidural sufentanil anesthesia: hemodynamic differences during induction of anesthesia and abdominal dissection in aortic surgery. AB - The present study was designed to compare the hemodynamic changes of epidural bupivacaine (EB) with epidural sufentanil (ES), supplemented by general anesthesia, in patients scheduled for abdominal aorto-iliac surgery. Twenty-eight ASA Grade 2 patients randomly received bupivacaine 0.5%, 1-1.5 mg kg-1 (n = 14) or sufentanil 150 micrograms (n = 14) epidurally at T12-L1, combined with light general anesthesia. Hemodynamics were measured before (T1) and after (T2) injection of EB or ES, after induction of general anesthesia (T3), and during the aortic dissection period (T4). EB or ES injection both produced a significant decrease in systolic, mean and diastolic blood pressure, left ventricular stroke work index (LVSWI) and coronary perfusion pressure (CPP). The induction of general anesthesia caused a significant fall in heart rate (HR) and cardiac index (CI) in the ES group. Abdominal dissection restored systemic pressure and cardiac index in the ES group. It was concluded that both ES and EB provided adequate analgesia and hemodynamics during tracheal intubation and abdominal dissection for aorto-iliac surgery. PMID- 1300858 TI - Double burst stimulation for monitoring profound neuromuscular blockade: a comparison with posttetanic count and train of four. AB - Double burst stimulation (DBS) is a new nerve stimulation pattern introduced to facilitate tactile evaluation of recovery from neuromuscular blockade. DBS consists of two bursts of high frequency stimulations separated by a short time interval. The relationships between DBS, post-tetanic count (PTC) and train-of four (TOF) on the evoked twitch response was investigated in 16 surgical patients and 7 intensive care patients given atracurium for muscle relaxation. A significant correlation between the twitch height of the first response to DBS and the number of post-tetanic responses was demonstrated when PTC was more than five (r = 0.47, p < 0.0003). When the first twitch of TOF was still not measurable, the first twitch of DBS ranged from 0 to 20% of the TOF-control twitch height. Furthermore the DBS ratio was significantly correlated to the TOF ratio (r = 0.92-0.96, p < 0.0002). It is concluded that DBS not only can be used for monitoring of recovery from neuromuscular blockade, but also for monitoring of intense degrees of neuromuscular blockade. PMID- 1300860 TI - [Behcet's disease and its treatment]. PMID- 1300859 TI - The pathogenic role of anti-neutrophil cytoplasm autoantibodies. PMID- 1300861 TI - Anti-neutrophil cytoplasm antibodies in patients with giant cell arteritis and/or polymyalgia rheumatica. AB - Anti-neutrophil cytoplasm antibodies (ANCA) were detected at low titers by indirect immunofluorescence in 1 out of 13 patients with giant cell arteritis (GCA) alone, 7 out of 30 with polymyalgia rheumatica (PMR) alone and 4 out of 15 with GCA plus PMR (8, 23 and 27%, respectively). Anti-myeloperoxidase antibodies were also demonstrated by an enzyme-linked immunosorbent assay in 4 patients with GCA alone (31%), 13 with PRM alone (42%) and 5 with GCA plus PRM (33%). The C reactive protein response was significantly higher (p < 0.05) in ANCA-positive than in ANCA-negative patients. PMID- 1300862 TI - [Anti-cardiolipin antibodies in Horton's disease]. AB - A prospective study on 11 patients with temporal artery biopsy-proven arteritis examined the frequency and significance of anti-cardiolipin antibodies. Antibody levels in 7 patients were higher than 20 units but were not correlated with an inflammatory syndrome, as assessed by measurement of 4 inflammatory proteins (fibrinogen, C-reactive protein, orosomucoid and haptoglobin). These 7 patients were treated with steroids and their antibody levels returned to the normal range after 4 to 16 weeks of therapy, later than the inflammatory proteins. Two patients had slight increases of their anti-cardiolipin antibody levels, but no signs of clinical relapse or increases of inflammatory proteins were observed. In this study, no correlation was found between the presence of anti-cardiolipin antibodies and the occurrence of ischemic complications in 6 of the 11 patients. PMID- 1300863 TI - [Bolus of cyclophosphamide and methylprednisolone in uveitis in Behcet's disease. Preliminary results with the use of new criteria of evaluation]. AB - In a prospective open trial, the effect of pulse cyclophosphamide or methylprednisolone in the treatment of Behcet's disease uveitis was studied. The therapeutic effect was evaluated based on two scores: one evolutive, reflecting ocular inflammation and calculated for each eye before and after therapy; and the other, a measure of disease severity, which took into consideration the irreversible damage. Patients who received cyclophosphamide pulse therapy (n = 8) had significantly lower evolutive scores (16.12 +/- 3.95, vs 10.37 +/- 8.53, p < 0.01) than the patients receiving classical methylprednisolone pulse therapy (n = 20), who had no significant changes in their evolutive scores (12.95 +/- 8.55, vs 10.05 +/- 8.56, p > 0.05). PMID- 1300864 TI - [Non-surgical treatment of kidney abscesses. Apropos of 12 cases]. AB - Twelve renal abscesses were treated with percutaneous aspiration (6 patients), percutaneous drainage (3 patients) or antibiotics alone (3 patients). The diagnosis was established based on computed tomography-guided aspiration in 9 cases and on radiographic findings and follow-up in the remaining 3. A bacterium was isolated in 2 out of 9 blood cultures, 2 out of 11 urine cultures and in all cultures of pus obtained by percutaneous aspiration. All patients had a good outcome. Our findings confirm the efficacy of percutaneous aspiration in the treatment of renal abscesses. Percutaneous drainage should only be considered when the abscess is very large or aspiration has failed. PMID- 1300865 TI - [An interview with Jean-Michel Dayer: what is going to happen tomorrow in the field of cytokines?. Interview by P Youinou]. PMID- 1300866 TI - [Endothelin, a vascular hormone]. PMID- 1300867 TI - [Gene-related peptide calcitonin. Actions and regulation]. PMID- 1300868 TI - [Genetics of human obesity]. PMID- 1300869 TI - [Consensus Conference. Prevention of infectious endocarditis. 1992 March 27- Paris]. PMID- 1300870 TI - Anti-neutrophil cytoplasm antibodies in giant cell arteritis and polymyalgia rheumatica. PMID- 1300871 TI - [Association of Wegener's disease and myelodysplastic syndrome]. PMID- 1300872 TI - [Erythroleukemia in a patient with Behcet's disease under long-term thalidomide therapy]. PMID- 1300873 TI - [B-cell lymphoma with paraneoplastic hypereosinophilia]. PMID- 1300875 TI - [Inflammatory syndrome disclosing aneurysmal or dissecting aortic pathology. Apropos of 3 cases]. PMID- 1300874 TI - [Pulmonary involvement in hypereosinophilic syndrome: tracheo-bronchial ulcerations reversible with cortisone bolus]. PMID- 1300876 TI - [Asphyxiating pulmonary edema, an uncommon manifestation of cardiothyrotoxicosis in a healthy heart]. PMID- 1300877 TI - [Association of asbestosis and scleroderma and polymyositis]. PMID- 1300878 TI - [Hodgkin's disease disclosed by erythema nodosum]. PMID- 1300879 TI - [Acute polyradiculoneuritis occurring during a recurrence of Hodgkin's disease]. PMID- 1300880 TI - [Metastasis in the psoas muscle disclosing breast carcinoma]. PMID- 1300881 TI - Removal of circulating tumor necrosis factor. Its role in septic shock treatment. AB - The tumor necrosis factor (TNF) is a polypeptide secreted by macrophages in response to endotoxins, especially from Gram-negative bacteria. Previous investigations suggest that TNF plays a prominent role in septic shock and meningococcal disease toxicity. A positive correlation was found between the initial serum TNF level and the patient's outcome. Despite the progress made in intensive care management and antibiotic therapy, the prognosis of septic shock remains very poor. Because of the implication of TNF in the pathogenesis of septic shock, we suggest that neutralization or elimination of this cytokine by plasma or blood exchanges could contribute to the treatment of severe forms of this syndrome. Five plasma exchanges and two blood exchanges were performed in 6 patients admitted for septic shock or purpura fulminans. Serum TNF levels were measured by immunoradiometric assay (Medgenix, ERIA Pasteur) before and after exchange. Serum TNF levels were found to be decreased by an average of 62% after the exchange. We conclude that exchange therapies are efficient in removing plasma TNF. Nevertheless, because of the limited number of patients treated, it is not possible to evaluate the clinical efficacy of such techniques. PMID- 1300882 TI - Plasma manipulation in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. AB - The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are syndromes of microangiopathic hemolytic anemia dominated by renal failure in children and by neurological signs in adults. Microvascular thrombosis is the typical lesion and endothelial injury is likely the initial event. Over the last 40 years, the prognosis has significantly improved, probably as the result of better supportive management of anemia, renal failure, hypertension, and electrolyte and water imbalances, but still remains poor in adults with renal arteriolar thrombosis and neurological involvement. Many specific therapies have been used and, based on reports of a few cases, a consensus has been reached empirically that recognizes antiplatelet agents and plasma manipulation as the most appropriate therapy for adult HUS and TTP. Their effectiveness, however, still remains to be formally tested in prospective controlled trials. Recently, we saw a 23-year-old man with a history of recurrent episodes of HUS in childhood and of TTP since the age of 21. HUS always disappeared following blood transfusions, whereas prompt remissions of the episodes of TTP were obtained with plasma exchange. In order to avoid the use of plasma, alternate forms of therapy were tried. However, aspirin (50 mg/day), prednisone (1 mg/kg bw/d), and human immunoglobulins (0.5 mg/kg/d) were ineffective, and plasma exchange was needed to obtain remission. During two more recent relapses, fresh-frozen plasma was infused as the initial therapy and produced a complete remission within few days, thus preventing the need for plasma exchange. During the last relapse, plasma exchange with albumin and saline failed to induce remission and plasma infusion was required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300883 TI - Adult hemolytic uremic syndrome with renal microangiopathy. Outcome according to therapeutic protocol in 53 cases. French Cooperative Study Group for Adult HUS. AB - We gathered data on adult patients suffering from hemolytic uremic syndrome with renal biopsy-proven thrombotic microangiopathy (n = 85) and excluded those associated with cancer, lymphoma, progressive systemic sclerosis and AIDS (n = 32). The 53 patients selected had a follow-up of more than 6 months (m = 38 months; range: 6-180 months). The aim of the study was to analyze the therapy dependent outcome in these 53 patients. In such a retrospective and multicentric survey, different therapeutic protocols were used, including plasma exchange (PE), infusions of fresh-frozen plasma, corticosteroids, IV immunoglobulins or supportive therapy alone; all were used differently. The 5 year patient and kidney survival rates were 90 and 60%, respectively, for the selected group. A better patient survival rate was observed in the PE-treated group, compared to all other patients without PE therapy (p < 0.03). In addition, for patients requiring dialysis at presentation, renal improvement was better in the PE treated group compared to patients receiving only supportive therapy (p = 0.05). When looking at the therapy-dependent outcome of renal function according to the pathologic type (glomerular, arteriolar or mixed), we observed that all PE treated patients with pure glomerular lesions recovered, unlike those with arteriolar or mixed lesions (p = NS). On the other hand, no long-term beneficial effects of "active therapy" (37 patients) compared to supportive therapy alone (16 patients) were observed on renal function, but the 2 groups were not completely comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300884 TI - Incidence and clinical profile of microvascular complications in renal allografted patients treated with cyclosporine. AB - The incidence of cyclosporine (CsA) vascular toxicity is open to debate. We attempted to evaluate the incidence of hemolytic accidents in our series of patients taking all clinical forms into consideration. From January, 1989, to December, 1990, 117 patients received kidneys from cadaver donors and were treated with CsA. Five patients presented hemolytic uremic syndrome (HUS) accompanied by a rejection crisis; 6 patients presented hemolytic anemia associated in 2 cases with marked thrombocytopenia without any evidence of rejection. Cytomegalovirus (CMV) infection was diagnosed in 2 patients and bacterial infection preceded hemolysis in 2 other cases, suggesting a triggering factor. In addition, when we systematically determined haptoglobin levels after introduction of CsA treatment, we found asymptomatic hemolytic episodes more frequently. Our incidence of hemolytic accidents was approximately 10%. Hemolysis could indicate ischemic vascular damage leading to arteriolar medial hyalinosis preceding fibrosis in CsA nephrotoxicity. Thus, it would be interesting to detect asymptomatic forms of hemolysis by monitoring haptoglobin levels. This approach could lead to a reduction of the CsA dose in patients presenting low haptoglobin levels, even in the absence of evidence of nephrotoxicity. PMID- 1300885 TI - Postpartum thrombotic microangiopathy with plasma exchange dependence. PMID- 1300886 TI - Anti-HLA antibodies depletion on protein A-sepharose columns in hyperimmunized patients awaiting renal transplantation. AB - To reduce anti-HLA immunization, 15 patients waiting for a renal graft received the following treatment: 5 to 7 immunoadsorption sessions on protein A-Sepharose columns, immunosuppressive drugs (corticosteroids 1 mg/kg (bw/day+cyclophosphamide 2 mg/kg bw/day) and iv polyclonal immunoglobulins. Before this treatment, panel-reactive antibodies ranged from 65 to 100% and antibody titers varied from 1/8 to 1/128. In all patients, antibody, titers were decreased. However, antibody resynthesis was incompletely blocked by this protocol. Eight out of 12 grafted patients had a functional kidney transplant 3 months to 3 years post-grafting. There early kidney failures occurred in the subgroup of 5 patients who had had historical positive cross matches prior to treatment. This treatment did not seem to increase the frequency of infectious complications before or after grafting. PMID- 1300887 TI - Anti-major histocompatibility complex antibody removal assay in a swine model. AB - A swine model of anti-MHC (SLA) immunization by skin grafting was established with the aim of removing preformed anti-MHC antibodies and preventing their resynthesis, in a situation close to that of hyperimmunization in humans. Plasma exchange therapy with or without associated immunosuppressive therapy was used. The feasibility of this animal model in terms of anti-MHC immunization and its therapeutic management have been proven. However, frequent early deaths of animals still mar the experimental protocol. Synchronization of plasma exchange and subsequent cyclophosphamide pulses seemed to abolish the antibody rebound phenomenon and cause marked drop of anti-MHC antibodies. Restimulation by a new skin graft is responsible for an intense polyclonal antibody stimulation, which suggests that we have to be careful in grafting patients with positive historical crossmatches and negative current ones. PMID- 1300888 TI - Effects of plasma-protein A immunoadsorption on idiopathic nephrotic syndrome recurring after renal transplantation. AB - Patients with end-stage renal failure secondary to idiopathic nephrotic syndrome are at risk of initial disease recurrence after kidney transplantation (30%). Selective proteinuria can appear immediately after transplantation and focal glomerular sclerosis with graft loss can occur in 10% of patients with recurrence. Current immunosuppressive protocols do not seem to influence the recurrence rate in adult patients and the efficacy of therapeutic plasma exchanges remains controversial. We have previously demonstrated that plasma exchanges, proposed early before glomerular sclerosis, were able to significantly reduce proteinuria without affecting albuminemia or glomerular filtration. We report here on three patients who suffered immediate recurrence after transplantation and were treated with plasma immunoadsorption onto protein A column (Excorim, Lund); these patients had prior histories of steroid-resistant focal glomerular sclerosis. This procedure is more specific than plasma exchange in that it cleared the serum of immunoglobulins, significantly decreased proteinuria in only two cases (from 14 to 5 g/d and 2.5 to 0.8 g/d) and eliminated it in the third case (from 3 to 0.1 g/d). The modifications of proteinuria levels appeared as early as the second immunoadsorption sequence and returned to pre-immunoadsorption values within 2 to 8 weeks. These observations argue for the protein A binding of plasmatic factor(s) involved in idiopathic, nephrotic syndrome and allow us to progress to the characterization of this(ese) factor(s). PMID- 1300889 TI - Ultraviolet light-induced immunomodulation: a possible new tool in organ transplantation. PMID- 1300890 TI - Immunology of systemic vasculitis. PMID- 1300891 TI - Immunological pathways and plasma exchanges. PMID- 1300893 TI - Renal biopsy in multiple myeloma and in other monoclonal immunoglobulin-producing diseases. PMID- 1300892 TI - Role of interleukin-6 in multiple myeloma. PMID- 1300894 TI - From plasma exchange to plasma treatment. Current techniques and therapeutic modalities. PMID- 1300895 TI - Plasma exchange therapy in pediatric patients. Plasma filtration with a unipuncture technique. AB - Therapeutic apheresis in children is limited by technical considerations, such as circuit blood volume, venous access and hemodynamic instability. Here we report our experience with 310 plasma-filtration sessions in 44 children (aged 9 months 17 years). We used a miniaturized circuit with a unipuncture technique and a "balancing system" which assured a permanent fluid equilibrium. This procedure is well adapted to children and always made pediatric plasma exchange therapy easier and safer. The more common indications remain Guillain-Barre syndrome and acute severe glomerular diseases. PMID- 1300896 TI - A new device for specific extracorporeal immunoadsorption of anti-DNA antibodies. In vitro and in vivo results. AB - Selective removal of anti-DNA antibodies could be an alternative to therapeutic plasma exchange in patients with active systemic lupus erythematosus. The method is based on the immobilization by covalent binding of double-stranded, calibrated, 0.3-kb DNA fragments on a microporous, methylated, polyacrylonitrile membrane. This enables linkage of 60 micrograms of DNA per cm2 of apparent surface area. In vitro, perfusion of 100 ml of plasma maintained at 37 degrees C through 650 cm2 of dsDNA linked to the membrane, at a flow rate of 1.5 ml/min for 60 min, resulted in the removal of 49-89% of anti-DNA IgG without any changes in plasma protein or IgG levels. During a therapeutic plasma exchange, perfusion of the plasma through 1.5 m2 of membrane, at a flow rate of 25 ml/min, initially removed 92% of the anti-dsDNA antibodies entering the adsorbent and 25% at 120 min, indicating a progressive saturation of the binding capacity. Clinical immunoadsorption, at a plasma flow rate of 20-40 ml/min through 2 m2 of membrane, removed more than 50% of anti-dsDNA IgG within 60 min. Microporous membranes are able to irreversibly bind large amounts of antigenic ligands, and enable the selective removal of pathogenetic immunoglobulins or circulating factors. PMID- 1300897 TI - Severe bleeding after cascade filtration apheresis for type II cryoglobulinemia related rapidly progressive glomerulonephritis. PMID- 1300899 TI - [Therapeutic strategy in fresh lesions of the exterior cruciate ligament of the knee]. PMID- 1300898 TI - [What role is left to surgery in portal hypertension?]. AB - The place of surgery in the treatment of gastrointestinal haemorrhage in cirrhotic patients remains controversial. Emergency surgery may be considered when other haemostatic techniques fail. In this situation, the decision to operate must be taken rapidly, as the prognosis depends on the patient's preoperative status and the degree of hepatocellular failure (HCF). Elective surgery for portal hypertension completes with long-term sclerotherapy, and randomised prospective comparative studies have not been able to clearly distinguish between the two methods. The objective of the various operations proposed is to prevent recurrent haemorrhage without inducing any mortality or major morbidity (particularly encephalopathy). Partial, selective anastomoses and devascularisations appear to satisfy these objectives. The choice of technique depends on the portal flow rate, the type of varices, the degree of HCF and the surgeon's experience. Lastly, liver transplantation should be considered when portal surgery is decided in order to select a procedure which does not compromise the possibility of future transplantation and also as an alternative to portal surgery, particularly in young subjects with already severely impaired liver function. PMID- 1300900 TI - [Calibrated latero-lateral portacaval anastomosis in the treatment of digestive hemorrhages by portal hypertension in the cirrhotic patient]. AB - The calibrated side to side portocaval shunt was described in 1979 by P. Marion. This type of shunt preserves a hepatopedal blood flow by maintaining portocaval pressure gradient superior to halve of the initial gradient. Twenty nine shunts were performed from 1981 to 1989 in patients with hemorrhagic liver cirrhosis alcoholic in 83 percent of cases). Two patients were in Child Pugh C class (7%), six procedures were performed as an emergency (21%). The operative mortality was nil. The hepatopedal blood flow assessed by direct venous angiography was maintained in 66% of cases at one year and 22% at five years. The actuarial survival rate without recurrent bleeding was 96% at two years, 88% at five years. Severe chronic encephalopathy was noted in three cases (10.3%). One patient was successfully treated by surgical anastomotic tightening with disappearance of the hepatic encephalopathy. The actuarial survival rate without encephalopathy was 82.7% at five years. The side to side calibrated shunt is a technically easy procedure with low mortality, low incidence of thrombosis and clinical results similar to the results of Warren's procedure. For these reasons, we have decided to include this procedure in our local protocol of management of hemorrhagic liver cirrhosis. PMID- 1300901 TI - [Prophylactic drainage after thyroidectomy: a randomized trial]. AB - A randomized clinical trial of surgical drainage in thyroid surgery was performed with 97 patients. Using equivalence testing it is reported that morbidity was not significantly different between the two groups and the length of hospital stay was shorter in the undrained group. It is possible to perform thyroidectomy without drainage in a selected population. PMID- 1300902 TI - [Esophagectomy for advanced malpighian cancer of the thoracic esophagus. Esogastric anastomosis in the neck or in the thorax? Late results of a "randomized" prospective study]. AB - During a 2 1/2 year period, 60 consecutive patients with cancer of the thoracic esophagus were randomized to undergo cervical (CA) or thoracic (TA) esophago gastrostomy. The tumors were staged post-operatively and were almost equally distributed between the two groups. The esophageal specimens were macroscopically studied on the fresh specimens with vital staining, then microscopically. The prevalence of peri-tumoral mucosal and sub-mucosal lesions was confirmed. Microscopic malignant invasions of esophageal sections were more frequent in TA (10) than in CA (3). Resected positive lymph nodes were more numerous in CA (17) than in TA (7). The mortality was identical in the two groups. Respiratory complications and recurrent laryngeal nerve trauma were more frequent in CA. Long term survivors had N0 disease with a healthy esophageal section. Even though subtotal esophagectomy reduces the prevalence of microscopic esophageal wall invasion at the upper section level and allows more complete unilateral exploration and resection of invaded lymph nodes, it offers no significant benefit concerning survival of patients with advanced cancer and malignant lymphadenopathy, after resection with post-operative radiotherapy. PMID- 1300903 TI - [Ivor Lewis' operation for epidermoid cancer of the esophagus. Immediate and late results. Apropos of 168 cases]. AB - 168 Ivor Lewis operations for squamous carcinoma of the lower esophagus are reviewed. 155 men and 13 women with a mean age of 59 years were operated on. 46 tumors were stage I and II, and 122 were stage III. Operations were considered to be curative for 120 patients and only palliative for 48. An esophagectomy associated with lymphadenectomy was performed through laparotomy and right thoracotomy. Feeding jejunostomy and pyloroplasty were routine. EEA or ILS 25 staplers were used to perform esophagogastric anastomosis and the gastroplasty tube was fashioned by TA 90 stapler. In every case an extended esophagectomy was performed with anastomosis between 3 ans 7 cm below the pharyngo-esophageal junction. Postoperative mortality was 4.7%. There were 10 leaks (6%) and 28 pulmonary complications. Median actuarial survival is 17 months. Actuarial survival at 2 years is significantly greater for stages I and II (68.4%) than for stage III (23.2%) (p < 0.01). Ivor Lewis esophagectomy is a reliable procedure to treat squamous carcinoma of the lower two thirds of the esophagus ensuring a good quality of life. PMID- 1300904 TI - [Appendiceal carcinoid tumor of systematic detection. When to propose right hemi colectomy and how to monitor? Thoughts apropos of a case and review of the literature]. AB - In relation to a case of carcinoid tumor of the appendix discovered after appendectomy and already metastatic, we discuss the prognostic factors of these lesions. Size is the most important one. For tumors less than two centimetres diameter, site, mesoappendix and lymph node involvement do not fully summarize the aggressiveness of the disease. We would like to emphasize the poor prognosis of perineural involvement, especially for young patients, in order to discuss the indication for salvage right colectomy. A positive reaction to Neuron-Specific Enolase allows this enzyme to be proposed as a postoperative serum marker. PMID- 1300905 TI - [Digestive surgery in patients over 80 years of age. Apropos of 690 operations]. AB - Between January 1981 and December 1990, 690 patients over the age of 80 years underwent gastrointestinal surgery. These operations were performed for diseases of the biliary tract in 248 cases (28%), colon or rectum in 238 cases (27%), stomach or duodenum in 130 cases (15%), small bowel in 32 cases (1.6%), oesophagus in 16 cases (1.8%), and for peritoneal carcinologic dissemination in 26 cases (3%). Emergency operation was performed in 43% of patients. Surgery was considered to be curative in 61% of patients. Overall postoperative mortality was 23%. The six following factors were associated with increased mortality: age over 85 years, ASA categories 3, 4, 5; surgery for malignant disease, peritonitis, palliative surgery, emergency surgery. PMID- 1300906 TI - [One hundred and twenty-five consecutive choledochotomies for suspected lithiasis without mortality. Current state of complications from common bile duct surgery]. AB - The postoperative courses of 125 consecutive surgical common bile duct explorations performed between 1983 and 1990 were analysed. All cases of common bile duct lithiasis, but three, were operated on. Intraoperative cholangiography was performed in 98 percent and cholangioscopy in 92 percent of patients; common bile duct stones were found in 95 patients (76 percent); the common bile duct was sutured without drainage in 78 patients (58 percent). There were no deaths. Morbidity was 14 percent, of which 10 percent were serious. Four percent of common bile ducts retained stones. The specific morbidity was 4 percent. These results confirm the reliability of surgical management of common bile duct stones and therefore should be considered for the evaluation of new procedures, such as laparoscopic treatment of common duct stones, or combined laparoscopic cholecystectomy and endoscopic sphincterotomy. PMID- 1300907 TI - [Ovarian metastases from colorectal cancers. Current place of prophylactic bilateral ovariectomy]. AB - Ovarian metastases occur in the course of colorectal adenocarcinomas on 3 to 14% of cases. They are bilateral in 50-70% of cases and frequently occult (6 to 25%) and constitute a factor of poor short-term prognosis (median survival: 18 months). After analysing the features of ovarian metastases from colorectal cancers, the authors discuss the current place of prophylactic bilateral oophorectomy in terms of its indications and results. Although this procedure should clearly be performed routinely in postmenopausal patients, it is more controversial in women of reproductive age who, according to some authors, nevertheless constitute a group at high risk of ovarian metastases. The contribution of this prophylactic oophorectomy to the improvement in the prognosis of colorectal neoplasms has not been statistically established to date and needs to be demonstrated by means of prospective studies. PMID- 1300908 TI - [Place of locoregional spinal anesthesia: indications and possibilities]. PMID- 1300909 TI - [External biliary fistula after right lateral sectorial hepatectomy for liver injury. Recovery by cholecysto-fistulous anastomosis]. AB - An external biliary fistula persisting for 14 months after right lateral hepatectomy for liver trauma is reported. Recovery was obtained by an unusual technique: the fistulo-cholecystostomy. PMID- 1300910 TI - [Muir-Torre syndrome. Apropos of a case associated with a familial form of cancer]. AB - We report the case of 41 year-old male patient, in whom multiple and recurrent infrequent cutaneous lesions (sebaceous adenomas) led to suspect the diagnosis of Muir-Torre syndrome. This diagnosis was confirmed when 2 colo-rectal adenocarcinomas were discovered and curatively excised (trans-anal excision, followed by total colectomy). The Muir-Torre syndrome was part of a familial cancer syndrome in this case, as the patient's mother and brother died from colonic cancer before the age of 45. The case-report underlines the diagnostic role of cutaneous lesions in this syndrome, allowing early detection of internal malignancy. PMID- 1300911 TI - [Signet-ring cell adenocarcinoma involving the bladder and the rectum. Apropos of two cases]. AB - Two cases of primary signet-ring cell carcinoma involving the urinary bladder, with invasion of the rectum, are presented. Pelvic exenterations were performed, followed by a rapidly fatal outcome (6 and 7.5 months). These cases of signet ring cell carcinoma of the bladder were reviewed with 33 previously reported cases in the literature. The clinical characteristics, histologic findings, pathogenesis, and effectiveness of aggressive treatment of this rare bladder malignancy are discussed. PMID- 1300912 TI - Rheological leukocyte indexes in diabetes mellitus type II. AB - Eleven healthy volunteers were examined, as well a thirty-five diabetic subjects divided into three groups according to the presence or absence of macro microvascular complications and according to whether or not these complications were chronic. The results of our study show a marked unfavorable in cell rheology in the diabetic subjects, as studied using the St. George filtrometer. In particular, polymorphonuclear (PMN) cells, in the diabetic subject showed a substantial decreases in viscosity and elasticity, reflected by decreased IrFr and increased CR values. These changes were most marked in the group of diabetics with acute vascular events, i.e., AMI and stroke. Rheological indexes studied appeared to be independent from the simultaneous blood glucose level. PMID- 1300913 TI - [Arteritis of the lower limbs in diabetics]. AB - 37 cases of diabetic arteritis of lower limbs in diabetic patients were retrospectively studied, from 1988 to 1991. Mean age was 66 years. Masculine predominance was evident with a sex ratio of 1/10. The majority of our patients have consulted at a late stage with trophic disturbance of inferior limbs, indeed 18 patients were seen at the 4th stage. Mortification was observed in 55% cases. Arteriography has allowed to show an elective localization of lesions at the femoralis arteria, profunda femoralis arteria and distal axes. Operative indication was made in 22 patients. Conservative surgery was performed for 50% of the operated patients. Conservative surgery results had been relatively less satisfactory than for others arteritis, particular because of late consultation and the condition of diabetic patients. PMID- 1300914 TI - [Arrhythmogenic cardiomyopathies of the right ventricle]. AB - Arrhythmogenic cardiomyopathies of the right ventricle (ACRV) are defined by an association of left delayed type ventricular arrhythmias, ranging from apparently uncomplicated extrasystoles to more severe or even potentially lethal arrhythmias such as polymorphous VT and ventricular fibrillation, with an anatomical substrate consisting of adipose or fibro-adipose degeneration of the myocytes of the free wall of the ventricle, which may be either focal (in particular: apex, anterior surface of the infundibulum and the sub-tricuspid region), or more diffuse. It is then accompanied by RV systolic dysfunction with dilatation of the cavity. This apparently well defined clinico-pathological entity is in fact more complex, if only because of the existence of associated lesions of the left ventricle in 1/3 of cases. The distinction from Uhl disease remains blurred, in particular in diffuse forms. It is most probable that more than one etiology is involved. A dysgenetic mechanism with probable autosomal dominant transmission has apparently been shown in familiar forms which are associated with a particularly severe risk of progression. The hypothesis of sequelae of multifocal myocarditis appears to be the most probable in sporadic forms. In the absence of histological criteria, which it is difficult to demand in view of the variability of results and potential dangers of endomyocardial biopsy involving such thin and fragile ventricular walls, the diagnosis of ACRV is based upon the concomitant existence of: (1) electrophysiological criteria: ventricular arrhythmias, in particular sustained monomorphous VT, with the particular feature of a very high degree of sensitivity to adrenergic stimulation (exercise), the existence of late potentials on the high amplification ECG, a highly specific sign, though unfortunately of poor sensitivity in localized froms, those which are most difficult to identify (2); segmentary morphological and kinetic RV abnormalities, most often resulting in localized akinetic or dyskinetic parietal vaulting, with stasis "in situ". Modern imaging methods (echocardiography, angioscintigraphy with phase analysis, nuclear magnetic resonance imaging, etc.) unfortunately do not yet offer an alternative to selective cineangiography of the RV which is the reference investigation when it is performed and interpreted under strict conditions. Several reports of sudden death or of ventricular fibrillation seen in confirmed cases of ACRV, as well as the publication of a number of autopsy registers indicating that this condition is one of the primary causes of sudden death in young individuals and in athletes, have cast doubt on the benign prognosis initially attributed to this condition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1300915 TI - [Non-invasive imaging in aortic dissection]. AB - Previously with a drastic prognosis, aortic dissection has extensively benefitted from advances in medical and surgical treatment, as well as progress in methods of investigation. While aortography is classically the reference special investigation, non-invasive methods now have a place of choice both during the acute phase (transthoracic and transesophageal echocardiography) and the chronic phase or for the purpose of post-operative monitoring (CT scan, magnetic resonance imaging). In an emergency context, the most important point is to diagnose a type A dissection, involving the ascending aorta, the treatment of which is surgical. In the majority of cases the diagnosis can now be made on the basis of transthoracic and transesophageal echocardiographic findings, which also enable identification of the site of the portal of entry, extension and concomitant lesions, all important features to be taken into consideration regarding surgical tactics. PMID- 1300916 TI - [Obstructive sleep apnea syndrome in adults and cardiovascular risk]. AB - Sleep obstructive apnea syndrome (SOAS) is a common condition with a strong male predominance. Its incidence is more than 1 percent in the population as a whole. It exists in snorers. Both snoring and SOAS are linked to the presence of abnormalities (congenital or acquired) of the upper respiratory tract. The nocturnal cardiovascular consequences of SOAS are directly linked to apnea. Bradycardia occurs during apnea and tachycardia when ventilation restarts. Paroxysmal nocturnal hypertension is a constant feature. Even in individuals who are normotensive during the day, each restarting of ventilation is accompanied by peaking of blood pressure. The pulmonary artery pressure curve follows that of systemic blood pressure. Complications begin when SOAS has been present for several years: 1) Chronic: permanent systemic hypertension is common (56 percent of SOAS). It is often refractory to antihypertensive treatment. 2) Acute: the onset of myocardial infarction and of cerebrovascular accidents explains the heavy mortality of SOAS (37 percent at 8 years in untreated individuals with a number of episodes of apnea exceeding 20 per hour of sleep). Other acute complications are less common: acute pulmonary edema, nocturnal sudden death. These events may be prevented by treatment suppressing apnea: actuarial survival curves are then superimposable upon those of the population as a whole. Thus SOAS is a cardiovascular risk factor which is remarkably reversible by specific treatment, though which most often passes unrecognized. PMID- 1300917 TI - [Value of new isotopes in cardiology]. AB - Nuclear Cardiology has seen many advances in the past few years: new indications for tracers already known, but also the appearance of new markers, by single photon imaging or by position emission (PET). With regard to the investigation of myocardial perfusion, thallium remains the most widely used isotope. Its sensitivity in the diagnosis of coronary disease is improved by the use of scintigraphic CT scan (SPECT) and excellent predictive value in terms of the onset of coronary events or mortality has been confirmed in particular. At the same time, the sensitivity and specificity of new technetium markers have been better defined. The investigation of myocardial metabolism, accessible up to now only via PET and confined, in France, to the domain of clinical research, is in the process of becoming a tool suitable for use by clinicians as a result of new SPECT-Thallium protocols (reinjection, late redistribution and rest), but also because of the development of single photon markers of myocardial viability, e.g. iodinated fatty acids. A functional approach to coronary disease, indispensable adjuvant to the anatomical approach, is now possible on a routine basis. PMID- 1300918 TI - [Pregnancy and cardiovascular agents]. AB - Any treatment used in pregnant women must take into account the effects of the substance in question of the fetus and the particular sensitivity of the latter during the first three months of development. The majority of drugs used in cardiology can be prescribed during pregnancy: digitalis preparations, furosemide, certain beta-blockers, verapamil, nifedipine (except during the first three months), quinidine, disopyramide, lignocaine, flecainide, amiodarone, heparins (non-fragmented and low molecular weight), central antihypertensive agents, dipyridamole and aspirin. In contrast, some drugs should be avoided because of insufficient information regarding their maternal and fetal consequences (bumetamide, modamide, the most recent beta-blockers, cibenzoline, ticlopidine) or because of harmful adverse effects on the fetus (spironolactones, bipyridines, diltiazem) or the newborn infant (angiotensin converting enzyme inhibitors). Finally, with certain medications (propafenone, oral anticoagulants), it is important to be able to compare maternal risks due to the disease and fetal risks induced by the drug. Modification of the conditions of use of these drugs and very careful monitoring of the patient most often suffice to avoid untoward events or complications with potentially serious medicolegal consequences and which may implicate the liability of the prescriber. PMID- 1300919 TI - [Diagnostic and therapeutic strategy in patients with multiple arterial disease]. AB - Concomitant coronary and peripheral lesions are common, in particular in candidates for peripheral surgery. Coronary lesions dominate the prognosis in all cases. The later mid- and long-term risks of such associations is far greater than the immediate operative risk. Each type of surgery, peripheral or coronary, offers the opportunity for arterial evaluation of the other area in its own right, rather than because of the surgical context. No invasive investigations should be routine. The diagnostic approach is guided by clinical data and to a lesser degree by non-invasive investigations, the discriminant nature of which is unfortunately poor in the context of coronary evaluation. Indications for multifocal simultaneous or sequential revascularization procedures, by surgery or angioplasty, are in fact small in number. They are wide ranging and must be discussed case by case, taking into account age, general condition, the emergency context and the type and severity of lesions. PMID- 1300920 TI - [Metabolic changes in cardiac failure]. AB - As soon as there is evidence of left ventricular dysfunction, even before clinical signs of chronic cardiac failure (CCF) have developed, intrinsic and extrinsic compensatory mechanisms are brought into play by the body. The majority of these mechanisms are under the influence of neurohumoral systems. When neurohormonal responses persist, as in CCF, they take on a beneficial nature since they participate in adaptation of the cardiovascular system as a whole, but they are also harmful since they worsen the working conditions of the myocardium by their cardiac and peripheral effects. Hyperactivity of the noradrenergic sympathetic nervous system is seen in CCF with levels 2 to 3 times higher as compared with subjects with normal left ventricular function. The circadian rhythm of catecholamines is modified. The increase in circulatory catecholamines is all the greater when cardiac failure is advanced. This release of noradrenaline (NA) is under the control of arterial baroreceptors which normally send to the central nervous system inhibitory inflow from the sympathetic nervous system. Inhibitory tone is released in case of a fall in blood pressure. Noradrenaline acts on beta-predominant myocardial receptors (inotropic and tachycardic) and alpha-predominant vascular receptors, resulting in arteriolar vasoconstriction. There is rapid onset of down regulation of myocardial beta receptors. This fall essentially concerns beta 1, but beta 2 also, since they may be affected according to the etiology of CCF (ischemia). The Renin Angiotensin System (RAS) is also activated by the fall in systemic blood pressure. This consists of a cascade of reactions leading to the synthesis of angiotensin II responsible for powerful vasoconstriction of all arterial areas, including the coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300921 TI - [Evaluation of the risk of arrhythmia after infarction]. AB - Evaluation of the risk of arrhythmias after myocardial infarction involves identification of those patients at a high risk of arrhythmic events, i.e. those who fall victim to ventricular tachycardia or sudden death. Such identification is an essential first stage before any treatment can be proposed. It has been clearly shown that the existence of premature ventricular contractions following infarction is an indicator of poor prognosis. In addition to evaluation of premature ventricular contractions, a Holter record can identify sinus variability, a parameter which the prognostic importance is currently being increasingly emphasized. Electrocardiography with averaging and high amplification has now been shown to be of value in the evaluation of arrhythmic risk after infarction. The negative predictive value of this investigation is very high, of the order of 90 percent. In addition to Holter and electrocardiography with averaging, two other non-invasive investigations can be used to determine arrhythmic risks after infarction. Stress testing can seek the presence of premature ventricular contractions related to exercise, while isotope ventriculography measures the value of ejection fraction which, in itself, has a high predictive value in terms of arrhythmic events. Mortality after infarction is proportional to the lowering of ejection fraction and among deaths approximately half are probably due to arrhythmias. Programmed ventricular pacing also has a role to play in evaluation of arrhythmic risk after infarction, but should not be routine. It may be indicated in those patients showing all of the signs of risk, i.e. repetitious forms by Holter, late potentials and low ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300922 TI - [Efficacy and tolerability of isoptine LP in mild to moderate hypertension. A multicenter study with 50 patients]. AB - A multicenter open trial involving 50 hypertension patients enabled evaluation of the efficacy and tolerability of Isoptine L.P. (sustained release verapamil) in mild to moderate essential hypertension. Following a 2-week placebo run-in period, patients were given Isoptine L.P. (240 mg/24 h) as a morning dose for 3 months, with a possible dose increase (360 mg/24 h) in case of diastolic blood pressure of 95 mmHg or more at the 30-day evaluation. Blood pressure was measured by mercury sphygmomanometer and, in 20 patients, by a Dinamap type Automatic device. After 3 months of treatment, blood pressure levels in supine and standing position, measured manually and automatically, showed a highly significant decrease, with a mean fall of 18.4 mmHg for systolic (13.7 percent) and 13.2 mmHg diastolic (-14.6 percent). 67 percent of patients were responders after 1 month of treatment and 79 percent at 3 months, including one-fifth at the dose of 360 mg/24 h. Seventeen patients, i.e. 34 percent, reported one or more adverse reactions. Among these, four patients had to stop treatment, twice because of headache and twice for constipation. Adverse events seen most frequently were constipation, headache, tiredness and vomiting. No cardiac adverse events were reported with the exception of one case of atrial premature contractions. The electrocardiogram revealed significant slowing of heart rate, as well as slight prolongation of PR and QT intervals and slight widening of the QRS complex. Tolerability on the basis of laboratory parameters was good. PMID- 1300923 TI - [My practice of thrombolysis in the acute phase of myocardial infarction in the light of extensive studies]. AB - Hospital mortality due to myocardial infarction has decreased markedly since the 1970's. Intravenous thrombolysis is certainly one of the reasons for this decrease but its precise role cannot be defined. In practice, major therapeutic trials enable definition of the broad lines. It is nevertheless essential to combine our personal experience with their analysis. It is not yet possible at present to say which is the best thrombolytic. Use of the association streptokinase-rtPA has the advantages of both agents and the same risks at a lower cost than that of rtPA alone. PMID- 1300924 TI - [Genes of resistance to aminoglycoside antibiotics in clinical strains of Serratia marcescens and the enzyme encoded by them]. AB - The patterns of aminoglycoside inactivating enzymes were determined by AGRP in 31 clinical isolated of Serratia marcescens. The results were compared with the data on identification of the aminoglycoside resistance genes by the specific DNA probes. It was shown that all the isolates of Serratia marcescens contained the AAC(6')-Ic gene which was not expressed in some isolates. The other detected aminoglycoside inactivating enzymes were the following: AAC(3)-V in 17 isolates, ANT(2'') in 7 isolates, AAC(3)-I in 4 isolates and APH(3')-I in 13 isolates. Reliability of the methods of AGRP and DNA-DNA hybridization was estimated in the assay of the aminoglycoside resistant clinical strains of Serratia marcescens. PMID- 1300925 TI - [Effect of antibiotics on Francisella tularensis]. AB - The minimum inhibitory concentrations of rifampicin, doxycycline, sisomicin, ciprofloxacin and phosmidomycin for various strains of Francisella tularensis were 0.5 to 2.0, 0.5 to 2.0, 0.125 to 0.4, 0.625 to 0.125 and 2.0 to 12.5 micrograms/ml, respectively. Ciprofloxacin and sisomicin had a marked bactericidal effect. The bactericidal effect of rifampicin was insignificant. Doxycycline and phomidomycin had practically no such effect. All the antibiotics had a post effect. The level of the post-antibiotic effect was different and depended on the antibiotic concentration. PMID- 1300926 TI - [Dynamics of drug resistance of Vibrio cholerae isolated from surface water reservoirs in Siberia and the Soviet Far East in 1976-1990]. AB - In the study on antibiotic resistance 1383 strains of El Tor Vibrio cholerae isolated from surface water reservoirs in 12 administrative territories of the Siberia and Far East within a period of 15 years were tested. The following antibiotics were used: ampicillin, streptomycin, monomycin, polymyxin, tetracycline, chloramphenicol, rifampicin and nalidixic acid. The resistance was unstable and its pattern was wave-like according to annual changes in the biological cycle. It was especially evident in regard to ampicillin, streptomycin, monomycin and polymyxin. The highest numbers of the strains were resistant to polymyxin, ampicillin and streptomycin (up to 100 per cent in some years). The lowest numbers of the strains were resistant to chloramphenicol (0.4 per cent) and tetracycline (1.9 per cent). No strains resistant to rifampicin and nalidixic acid were isolated. In some cases the antibiotic resistance level depended on the geographical zone where the strain was isolated. A direct quantitative dependence of the resistance level on the MIC was observed: the lower the MIC of the drug was, the lower the number of the strains resistant to it was. Within the 15-year period there was no general tendency to increase the resistance in V. cholerae to the antibiotics used. PMID- 1300927 TI - [Effect of subinhibitory concentrations of antibiotics on catalase activity of plague microbes]. AB - It was shown that the presence of subinhibitory concentrations of ampicillin, cefotaxime or gentamicin in the cultivation medium had a marked inhibitory effect on the catalase activity of plague microbe. The effect depended on the characteristic features of plague microbe strains and the incubation temperature. When the cells of a virulent strain of the plague microbe Y. pestis 1300 were cultivated at a temperature of 37 degrees C on a medium containing the subinhibitory concentrations of ampicillin or cefotaxime, the pathogen virulence for albino mice significantly decreased. PMID- 1300928 TI - [Antibiotic sensitivity of plague microbe strains from foreign countries]. AB - The method of serial dilutions on the Hottinger agar was applied to comparative assay of antibiotic sensitivity in 50 strains of the plague microbe isolated abroad and in 5 strains isolated in the plague focus in the Central Caucasus. The antibiotics used in the assay were the following: streptomycin, gentamicin, doxycycline, monomycin, kanamycin, tetracycline, erythromycin, ristomycin, lincomycin and polymyxin M. Irrespective of the origin, all the isolates were resistant to erythromycin, lincomycin and polymyxin M. The levels of the sensitivity to the other antibiotics were different. The data serve as a ground for the statement that there is no tendency to development of antibiotic resistance in the plague microbe in patients treated with high doses of the antibiotics and mainly streptomycin. Along with streptomycin, such antibiotics as gentamicin, tetracycline, doxycycline and kanamycin are useful in the therapy of plague and require further investigation. PMID- 1300929 TI - [Effectiveness of cefotaxime in experimental plague infection]. AB - Cefotaxime was shown highly efficient in prophylaxis and treatment of experimental plague infection in albino mice. The in vitro activity of cefotaxime against natural strains of the plague microbe was 32 to 64 times higher than that of cefazolin, cephalothin and cefmetazole. The combined use of cefotaxime with amikacin significantly increased the percentage of the survived albino mice with plague infection as compared to the use of the antibiotics alone. PMID- 1300930 TI - [Doxycycline in the prevention of experimental plague induced by plague microbe variants]. AB - A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague. PMID- 1300931 TI - [Effectiveness of phosphomycin and its combinations with amikacin and cefotaxime in experimental plague infection]. AB - When administered intramuscularly in doses of 8 and 16 mg/mouse, phosphomycin was highly active in the treatment of albino mice with experimental plague infection (80-100-percent protection of the animals from death). Combinations of phosphomycin with cefotaxime in inefficient or not sufficiently efficient doses had a synergistic effect. When the albino mice were treated with combinations of phosphomycin and amikacin, the percentage of the survived animals significantly increased in comparison to that after the use of the antibiotics alone. PMID- 1300932 TI - [Effect of protoplasting on antibiotic activity and resistance in the strain Streptomyces hygroscopicus 155]. AB - The influence of protoplasting and protoplast regeneration in the presence of polyethylene glycol on antibiotic activity, components of antibiotic complexes and antibiotic resistance in Streptomyces hygroscopicus 155 was studied. It was shown that the protoplasting and protoplast regeneration influenced the antibiotic activity. The protoplast fusion resulted in increased isolation of variants with higher antibiotic activity. The processes also affected the components of the antibiotic complexes but had no effect on the strain resistance to some antibiotics. PMID- 1300933 TI - [Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication]. AB - The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent). PMID- 1300934 TI - [Experimental rationale for the feasibility of using sulacillin for the prevention of infectious complications of combined radiation and thermal injuries]. AB - Concurrent radiation and thermal injury (IRTI) was simulated in Wistar rats. For prevention of the autoinfectious complications sulacillin, a combination of ampicillin and sulbactam, was used. The use of sulacillin was started on the onset of IRTI and continued for 7 days. The drug was administered intramuscularly twice a day. It was observed that the 8-day survival of the animals increased by more than 40 per cent and the statistical levels of bacteremia and bacterial endotoxemia significantly decreased. The experiments showed that sulacillin had no side immunodepressive effect and did not aggravate the affection of the blood system. The drug was recommended for further studies to provide evidence for rational schemes of antibacterial therapy in IRTI. PMID- 1300935 TI - [Etiology of inflammatory maxillofacial diseases and estimation of the effectiveness of antibacterial drugs in vitro]. AB - The results of identification of 710 clinical strains of anaerobic microorganisms isolated from the pathological foci of patients with maxillofacial diseases are presented. The species composition of the microflora associations in the cases with abscesses, phlegmon, lymphadenitis, osteomyelitis and parodontitis is described. Along with a high frequency of nonsporulating anaerobes, staphylococci, microaerophilic streptococci and in the cases with parodontitis actinomycetes, Bacillus licheniformis and Bacillus coagulans strains (1.6-15% of the isolated strains) were first detected in cases with various forms of the disease. Two groups of the drugs effective against the anaerobes were identified by the data on the antibiotic sensitivity. The lowest MICs along with the activity broad spectrum were defined for gramicidin, levomycetin and nitazol. PMID- 1300936 TI - [Antibiotic therapy in children with pertussis]. AB - The data accumulated within the last years required revision of the indications to the use of antibiotics in treatment of pertussis. One of the aims of antibiotic therapy in pertussis was to prevent colonization of B. pertussis in the respiratory tracts. With that end in view the choice of antibiotics should be limited by those, to which the pathogen is the most sensitive i.e. erythromycin, ampicillin and augmentin. Comparative efficacy of erythromycin and ampicillin during the first 2 weeks of the disease was studied in 79 infants at the age not older than 1 year with pertussis and it was shown that erythromycin was advantageous by its therapeutic activity and less side effects. Expedience of the antibiotic therapy during the spastic period for providing a preventive effect on development of bronchopulmonary complications was studied in 201 patients with pertussis. No preventive effect of the antibiotics on development of the bronchopulmonary complications defined by the secondary bacterial flora was recorded. In the group of the patients treated with the antibiotics prophylactically (group 1) the complications were 2.6 times more frequent than in the patients treated with pathogenetic agents alone (group 2). Intrahospital pneumonia developed in 8.9 per cent of the patients in group 1 and in 1.5 per cent of the patients in group 2. Therefore, antibiotics should not be used at the late periods of pertussis for prophylaxis of secondary bacterial complications. PMID- 1300938 TI - [Microbial ecology of humans and animals and cholesterol metabolism. 1. Evidence and mechanisms of host microflora participation]. PMID- 1300937 TI - [Methods of local antimicrobial therapy and prevention of postpartum endometritis]. AB - To increase the effect of the treatment of puerperal endometritis, long-term washing of the uterus cavity with cool solutions of furacillin was used in 57 puerpera. The most favourable results were observed in 27 patients who at the final stage of the washings were treated with antibiotic solutions administered to the uterus cavity. The recovery terms, as well as the terms of the hospitalization lowered. For confirming the diagnosis of endometritis and control of the therapy efficacy cytograms of the metroaspirates were used. High efficacy of the prophylactic administration of antibiotics to the myometrium tissues during the cesarean section with high risk of infectious complications was also shown. Both the methods were recommended for their wide use in obstetric hospitals. PMID- 1300939 TI - [Microbial ecology in man and animals and cholesterol metabolism. 2. Hypocholesterolemic effect of microorganisms]. PMID- 1300940 TI - [Influence of peroxidation products of liposomal lipids on antibacterial activity of liposomes]. AB - The dynamics of accumulation of lipid peroxidation products (LPPs) in suspensions of phosphatidyl choline-cholesterol liposomes at various acidity levels was studied. It was shown that intensity of the accumulation of LPPs was inversely proportional to the suspension pH. When the liposomes were incubated together with the cells of Pseudomonas aeruginosa, there was a decrease in the level of LPPs in comparison to that in the suspension which did not contain bacterial cells. The accumulation of LPPs in the incubation medium correlated with the bacteria death rate in the suspension. There was a direct relationship of the antibacterial activity of the liposomal suspension on its content of LPPs. PMID- 1300941 TI - Neurochemical and psychomotor interactions of new selective COMT inhibitors with clorgyline and nomifensine in levodopa-treated rats and mice. AB - The effects of three new catechol O-methyltransferase (COMT) inhibitors (nitecapone, entacapone and Ro 41-0960) were assessed on brain neurochemistry and psychomotor tests in levodopa/carbidopa-treated rats and mice. In neurochemical studies in rats, neither nitecapone (3 mg/kg) nor Ro 41-0960 (3 mg/kg) enhanced the levodopa/carbidopa (15/30 mg/kg)-induced dopamine levels in the hypothalamus and striatum, whereas 3-O-methyldopa (3-OMD) levels were suppressed. Adding clorgyline (8 mg/kg) elevated dopamine in the hypothalamus and striatum. 3,4 Dihydroxyphenylacetic acid and homovanillic acid levels were suppressed in the striatum and, to a lesser extent, also in the hypothalamus. Adding nomifensine (10 mg/kg) reversed the action of Ro 41-0960 on the 3-OMD levels and raised the homovanillic acid levels in the striatum. All COMT inhibitors (30 mg/kg) slightly enhanced levodopa/carbidopa (15/30 mg/kg)-induced hypoactivity in rats. Ro 41 0960 also augmented the effects of clorgyline and nomifensine on the locomotor activity. Levodopa/carbidopa (10/10, 25/25, 50/50, 100/100 mg/kg) dose dependently decreased rectal temperature, rotarod time and spontaneous motility in mice. Additional COMT inhibition (30 mg/kg) had only minor effects on behavior. Ro 41-0960 (30 mg/kg) potentiated several behavioral effects of clorgyline (4 mg/kg) in the levodopa/carbidopa (10/10 mg/kg)-treated mice. PMID- 1300942 TI - Influence of the endothelium on the responses to endogenous agonists in human internal mammary and gastroepiploic arteries. AB - The higher patency rate of internal mammary artery grafts compared to venous grafts has been ascribed to its endothelial function, namely a greater capacity to release endothelium-derived relaxing factor and to inhibit serotonin-induced contractions. Gastroepiploic and mammary arteries were obtained intraoperatively from 27 patients and suspended in organ chambers to record isometric tension. The relaxations to acetylcholine were similar in both vessels. The contractions to serotonin, normalized as a per cent of KCl (90 mM)-induced contractions, were 46 +/- 15% for the internal mammary artery and 18 +/- 5% for the gastroepiploic artery. Endothelium removal equally potentiated the responses to serotonin: the maximal responses (% of KCl) increased to 63 +/- 18% and 41 +/- 6%, respectively. The contractions to endothelin were also higher in the internal mammary artery: 166 +/- 19% vs 102 +/- 6% of KCl (p < 0.05), but were not affected by endothelium removal. However, the capacity to contract, expressed in tension developed, was higher in the gastroepiploic artery: the KCl (90 mM)-induced contraction was 2.6 +/- 0.3 g in the internal mammary vs 7.9 +/- 0.9 g in the gastroepiploic artery (p < 0.001). Histologically, similar wall thickness and paucity of atherosclerotic lesions were observed, but the medium was mainly elastic in the internal mammary and muscular in the gastroepiploic artery. Thus, despite a similar endothelial function and greater responsiveness of the mammary artery to endogenous vasoconstrictors when compared to a receptor-independent vasoconstrictor, the higher contractile capacity of the gastroepiploic artery might be a disadvantage in terms of graft function and patency. PMID- 1300943 TI - Simultaneous measurement of renal blood flow of the outer and inner cortex by laser-Doppler flowmetry in anesthetized dogs: effect of enalapril diacid. AB - Renal hemodynamic effects of the angiotensin-converting enzyme inhibitor enalapril diacid (30 micrograms/kg, i.v.; n = 8) were examined using laser Doppler flowmetry in anesthetized dogs. Two laser-Doppler flowmetry probes were applied simultaneously to measure the renal blood flow of the outer and inner cortex. Changes in cortical renal blood flow, obtained by the laser-Doppler flowmetry method, were intimately related to those in total renal blood flow measured with the electromagnetic flow probe during occlusion of the abdominal aorta or after administration of angiotensin II, norepinephrine, acetylcholine or dopamine. Enalapril diacid produced a significant increase in total renal blood flow, despite moderate hypotension. The blood flow of the inner cortex significantly increased by 21% following enalapril diacid, while that of the outer cortex did not. These data indicate that there may be a regional difference in the intrarenal vasodilating effect of enalapril diacid. These results also demonstrate that the laser-Doppler flowmetry method is suitable for the continuous measurement of directional changes in both outer and inner cortical blood flows. PMID- 1300944 TI - Epithelial modulation of antigen-induced tracheal smooth muscle contractions in actively sensitized guinea-pigs. AB - Coaxial bioassay system (guinea-pig trachea and rat anococcygeus muscle as donor and bioassay organs, respectively) and tracheal open ring preparations from ovalbumin-sensitized guinea-pigs were used to investigate the role of the epithelium in response to the antigen challenge. Ovalbumin induced concentration dependent relaxations in the phenylephrine precontracted rat anococcygeus muscle suspended in the lumen of sensitized guinea-pig tracheal tube preparations in the presence of either indomethacin or mepacrine. Removal of the epithelium abolished ovalbumin-induced relaxation responses. In tracheal open ring preparations, epithelium removal shifted the ovalbumin concentration-response curve to the left in both the control and mepacrine-treated experiments. Indomethacin significantly potentiated the ovalbumin-induced contractions in epithelium-intact preparations, while in epithelium-denuded ones no significant change was observed. In the presence of indomethacin, the maximum contractile responses were significantly higher in epithelium-intact preparations than in epithelium-denuded ones. These results provide direct evidence for the release of epithelium-derived relaxant factor(s), which is (are) neither a cyclooxygenase nor a lipoxygenase product, in response to the antigen challenge. In addition, the observation of the increased maximum contraction to antigen in epithelium-intact preparations in the presence of indomethacin, suggests the involvement of contractile influences derived from the epithelium in antigen-induced responses of airways. PMID- 1300945 TI - Glucagon enhances bile flow, bilirubin uridine diphosphate-glucuronyltransferase activity and biliary bilirubin monoconjugate excretion in the rat. AB - Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration. PMID- 1300947 TI - Topical antibiotics in cholecystectomy for gallstone diseases. AB - Efficacy of topical antibiotics in cholecystectomy for gallstone disease was evaluated. Forty-four patients who accepted topical single administration of 1 or 2 g each of latamoxef, cefmenoxime, cefotiam or cefamandole during operation were compared with 36 patients with systemic administration of cefem antibiotics by intravenous drip at a dose of 1 or 2 g, twice daily for postoperative 4 to 7 consecutive days. In topical administration group, concentration of each antibiotic in the gallbladder and common duct bile, gallbladder tissue, parietal peritonea and intra- and postoperative peripheral blood exceeded mostly MIC80 against bacteria usually existing in bile by biliary tract infection or bacteria by wound infection. There was no difference between the two groups in postoperative clinical course. Thus, an adequate prophylactic effect can be expected by topical use of antibiotic during cholecystectomy. PMID- 1300946 TI - Mitochondrial changes in phospholipid molecular species during the increased oxidative phosphorylation after hepatectomy. AB - The changes in liver mitochondrial and microsomal phospholipid molecular species were analyzed during the period of remarkably increased oxidative phosphorylation following partial hepatectomy in rabbits. At 24 hours after hepatectomy, phosphorylative activity increased significantly from 69.7 +/- 5.5 to 118.5 +/- 5.7 nmol of ATP synthesized/min/mg protein, compared to the sham operated group. The ratio of phosphatidylethanolamine to phosphatidylcholine (PE/PC) in mitochondria increased significantly in the hepatectomy group compared with the sham operated group. Remarkable changes in molecular species were observed in mitochondrial phosphatidylethanolamine. 1-Stearoyl-2-arachidonoyl species decreased in the hepatectomy group. On the other hand, microsomal phospholipids hardly changed compared with mitochondrial ones. The change in content of 1 stearoyl-2-arachidonyl phosphatidylethanolamine in mitochondria tended to return to normal levels concomitant with the normalization of phosphorylative activity. The changes in content of mitochondrial phospholipids, especially phosphatidylethanolamine, might also be related to enhancement of phosphorylative activity. PMID- 1300948 TI - [The effects of centrifugal pump on liver support system with porcine liver perfusion]. AB - The effects of vaneless centrifugal pump (Bio-pump P-80) on energy metabolism were studied, as compared with the roller pump, in an isolated porcine liver perfused with human blood for 6 hours. According to preliminary examination, flow rates were decided to 0.4, 0.8 ml/min/g in roller pump group, in Bio-pump pump group, respectively, not to increase more than 15 mmHg in initial portal pressure. During the perfusion, actual portal pressure was measured and circulatory resistance (portal pressure/flow rate) was calculated before perfusion and hourly after perfusion. Acetoacetate, beta-hydroxybutyrate, lactate and pyruvate, were measured at same times, from which values the ketone body ratio (acetoacetate/beta-hydroxybutyrate, KBR), reflecting the redox state of liver mitochondria, was calculated. In the Bio-pump group, in spite of its high flow, circulatory resistance was low at every hour during the perfusion. KBR was increased rapidly from 0.40 to 1.39, 2.59, 2.75, 2.38, 2.41, and 1.82 and lactate was decreased rapidly from 7.96 to 3.90, 1.77, 1.29, 1.33, 1.34, and 1.25 mmol/L at the respective hours after perfusion. There were significant differences at 2 and 4 hours after perfusion in KBR and after 2 hours of perfusion in lactate as compared with the roller pump group (p < 0.05). These results suggested that the Bio-pump is available for constant and high flow to the liver and helpful to elevate the mitochondrial NAD/NADH ratio (oxidized and reduced forms of free nicotinamide-adenine dinucleotides), leading to and enhancement of metabolic capacity of the perfused liver. PMID- 1300949 TI - [A case of retroperitoneal ganglioneuroma]. AB - A 50-year-old woman was admitted under a diagnosis of abdominal tumor. Ultrasonography and CT scanning were performed, and a right retroperitoneal tumor was detected. Absolute curative resection was performed. The resected tumor was 13.5 x 11.5 x 9.0 cm, and histologically diagnosed as ganglioneuroma. To our knowledge, 99 cases have been reported in Japan. During a twelve-month follow-up period, the postoperative course was uneventful and no recurrence had been noted. PMID- 1300950 TI - [Treatment of first restenosis by recurrent angioplasty. Immediate results and angiographic follow-up after 6 months]. AB - This report summarises the authors' experience of 421 patients treated for a first restenosis by repeat conventional balloon angioplasty with a high 6 months angiographic follow-up (84%). The immediate results were significantly less than those obtained during the same period with initial angioplasty procedures (94.5% success and 0.9% complications without any deaths during the hospital period). The 39.9% recurrent restenosis rate, on the other hand, is the same as observed after a first procedure. The risk factors of a second restenosis seem to be different from those of a first restenosis. A shorter interval between the first and second angioplasty (< 3 months) was associated with a 55% risk of restenosis compared with only 36% when the interval was > 3 months. Two operative factors were associated with a high risk of recurrent restenosis: a maximum inflation pressure > 7 atm and > or = 3 balloon inflations. These results seem to be important and should be taken into consideration when deciding on the management of patients presenting with a first restenosis. PMID- 1300951 TI - [Can patients with severe left ventricular dysfunction be treated by coronary artery bypass surgery?]. AB - Forty three men and 3 women, with an average age of 59 years (13 to 78 years) underwent aorto-coronary bypass surgery despite severe left ventricular dysfunction (ejection fraction < 35%); 96% of the patients had previous infarction; 60% (N = 28) had unstable angina, 52% (N = 24) had had pulmonary oedema or an episode of congestive cardiac failure. The average ejection fraction was 29 +/- 4%, range 17 to 35%. Thirteen patients had ventricular aneurysms, 4 had grade 3 or 4 mitral regurgitation. The coronary lesions were usually multivessel left main coronary (6), triple vessel disease (27), double vessel disease (12), single vessel disease (1). The average number of bypass grafts per patient was 2.3. The average aorting clamping time was 63 minutes (range 26 to 133 minutes). There were 4 mitral valve replacements, 4 resections of ventricular aneurysms and 1 double procedure (aneurysmectomy and valve replacement). The operative mortality was 2.1% (1 death). During an average follow-up period of 27 months (range 3 to 90 months), there were: 2 recurrent infarctions, 13 episodes of cardiac failure and 8 cardiac deaths (cardiac failure: 5, sudden death: 2, recurrent infarction: 1). Two patients underwent cardiac transplantation. The regression of angina (90% of operated patients were asymptomatic) and the low operative risk, justify aortocoronary bypass surgery despite left ventricular dysfunction in patients with severe symptoms (unstable angina, chronic, invalidating angina). The medium-term results indicate a high risk of cardiac failure which is partially responsible for the secondary mortality rate of 17% at 2 years. PMID- 1300952 TI - [VVI mode cardiac pacing: cause or risk factor of cerebral embolism?]. AB - Epidemiological studies suggest that VVI pacing is associated with a higher risk of embolic complications than atrial or dual chamber pacing. However, no studies have been performed on pacemaker patients admitted to a neurological department with a cerebral embolism. The authors report the cases of 8 patients (6 men and 2 women) with an average age of 74 years and having the following characteristics: 1) a cerebral embolism, 2) a permanent cardiac pacemaker (7 VVI and 1 DDD mode). The average delay between implantation of the pacemaker and the neurological complication was 31 months. Cardiological investigations at the time of admission showed: a clinically evident cause of cardiac embolism in 3 cases (2 with VVI and 1 with DDD pacing); paroxysmal or permanent atrial fibrillation in 4 cases with VVI pacing at the time of the embolic event (in only one case at the time of implantation); various echocardiographic abnormalities in 6 of the 7 patients who underwent this examination, mainly left atrial dilatation (6/7), septal wall motion abnormalities in all related to ventricular pacing and unexplained left ventricular dilatation in 2 patients with VVI pacemakers. These results suggest that although the etiology of cerebral embolism was probably multifactorial in some patients, VVI packing probably a predisposing role, though not the only cause, and could be considered to be an embolic risk factor as suggested by previous epidemiological studies. These preliminary retrospective data should be interpreted cautiously taking into account the small population size. Prospective studies on pacemaker patients with cerebral embolism are required. PMID- 1300953 TI - [Heart surgery in normothermia and aerobiosis: apropos of 530 patients]. AB - Between February and October 1991, 530 consecutive patients underwent myocardial revascularization or valvular surgery with warm continuous antegrade and retrograde cardioplegia (37 degrees C). Three hundred and thirty three patients had isolated myocardial revascularization, 159 valvular surgery alone and 25 had combined valvular and coronary bypass. The global mortality was 5.1%, 3.7% for coronary bypass, 7.5% for valvular surgery and 8% for combined valvular and coronary surgery. A multivariate analysis identified the "reperfusion time" as the only predictive factor of hospital mortality (p < 0.001). Intraortic balloon counterpulsation was required postoperatively in 3.2% of cases, 5.2% of coronary bypass and 0.8% of the valvular patients. Inotropic drugs were used to come off cardiopulmonary bypass in 16.5% of coronary and 37.5% of valvular patients. There were 0.9% perioperative infarctions: 1.2% in the coronary bypass cases and 0.6% in the valvular cases. Spontaneous return to sinus rythm was observed in 87.9% of cases. The average "reperfusion time" was 20.48 +/- 0.7 mn. Analysis of the influence of aortic cross clamp time on cardiac morbidity in two groups of coronary patients (Group I: short cross clamp time less than 60 mn; Group II: long cross clamp time, 60 to 33 mn) showed that the hospital mortality, the prevalence of the use of inotropic drugs and balloon counterpulsation the postoperative cardiac index, the rate of spontaneous de fibrillation and the reperfusion time did not depend on the aortic cross clamp time. Cardiac morbidity. PMID- 1300954 TI - [Value and limits of balloon laser-assisted angioplasty in the treatment of acute obstruction during percutaneous transluminal coronary angioplasty]. AB - One of the problems of percutaneous transluminal coronary angioplasty is acute occlusion during the procedure, the main cause of serious complications and emergency coronary bypass surgery. Acute occlusion is generally related to severe intimal dissection and/or thrombosis. In animal experiments, it is possible to treat intimal dissection and dessicate thrombi by balloon laser angioplasty. Using this method, a programmed laser energy may be delivered to the arterial wall via a fiber optic system linked to a Nd:Yag laser during classical balloon inflation. This has been proposed for the treatment of acute coronary occlusion. Between September 1989 and August 1990, 923 patients underwent coronary angioplasty at the Centre Cardiologique du Nord. Peroperative acute occlusions occurred 52 times (3.9%) in 52 patients. Sixteen patients who were "candidates" for emergency coronary bypass surgery (residual stenosis > or = 75%; delayed flow; myocardial ischaemia) were treated by laser balloon angioplasty, 14 with success (87%). Two patients had to be operated as an emergency. There were no hospital deaths. The average follow-up was 4.7 months for the 14 non-operated patients. Systematic control coronary angiography was refused by 2 asymptomatic patients. In the other 12 patients investigated 1 to 17 months after the procedure, there were 10 restenoses (76%), 6 of which were treated by repeat angioplasty and 3 by coronary bypass surgery. These results show that balloon laser angioplasty is very effective in the treatment of peroperative acute occlusions, enabling emergency coronary bypass surgery to be avoided in 87% of cases, but it is associated with a very high restenosis rate which is difficult to accept. PMID- 1300955 TI - [Calcium channel inhibitors and ventricular filling]. AB - Abnormalities of ventricular relaxation and compliance often precede changes in systolic function in ischemic and hypertrophic or hypertensive heart disease. Several studies using non-invasive methods have confirmed the beneficial effects of calcium channel blockers on left ventricular diastolic function in ischemic and primary hypertrophic cardiomyopathies. Their usefulness remains controversial in secondary cardiac hypertrophy such as in hypertensive heart disease. Improved left ventricular isovolumic relaxation and filling results more from the coronary and peripheral vasodilatory effects of calcium channel blockers than from a direct action on the cardiac muscle. PMID- 1300956 TI - [Effects of angiotensin II on intrinsic contractibility of the myocardium in the guinea pig]. AB - Analysis of the contraction-relaxation coupling of guinea pig left ventricular papillary muscle was performed with and without angiotensin II (Ang II 10-6 M). The inotropic and lusitropic properties of Ang II were evaluated at 20 degrees C, 30 beats/min, CaCl2 6H20 2 mM and pH 7.4, under low load (isotonic conditions) and high load (isometric conditions). The maximum velocity of contraction (max Vc) and relaxation (max Vr) were calculated from isotonic contraction having as its only load that corresponding to the imposed preload at Lmax. The maximum positive (+dF/dtmax) and negative values (-dF/dtmax) of the derivative of the force were calculated during isometric contraction. The coefficients, R1 = max Vc/max Vr and R2 = (+dF/dtmax)/(-dF/dtmax), were calculated. These two coefficients allow the contraction-relaxing coupling to be assessed at low and high loads respectively. In the presence of Ang II, the increase in the isotonic velocity of relaxation (1.93 +/- 0.26 vs 3.15 +/- 0.35 Lmax/sec; p < 0.001) was greater than that of the isotonic velocity of contraction (0.74 +/- 0.05 vs 1.02 +/- 0.07 Lmax/sec; p < 0.001). This results in a decrease in the ratio of the velocities of isotonic contraction and relaxation (R1) (0.44 +/- 0.06 vs 0.35 +/- 0.05; p < 0.01). Under isometric conditions, Ang II induced a proportional increase in the parameters of contraction and relaxation. Consequently, there was no significant change in the R2 coefficient (1.22 +/- 0.06 vs 1.12 +/- 0.08). Moreover, Ang II did not induce any change in the sensitivity of the relaxation with respect to load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1300957 TI - [Study of new thrombolytic agents in myocardial infarction: a multicenter randomized trial (APSAC versus rt-PA)]. AB - A hundred and eighty three patients with a primary myocardial infarction less than 4 hours old were included in a double blind trial versus placebo comparing an isolated plasminogen streptokinase activator complex (APSAC: 30 mu in 5 mn) and tissue type plasminogen activator (rt PA: 10 mg bolus followed by 90 mg in 130 mn). Clinical evolution, side effects, patency of the artery responsible for infarction, left ventricular contractile function (contrast angiography on the 7th day and angioscintigraphy on the 21st day) and infarct size were studied. The two groups were comparable in age (54 +/- 11 years), delay in randomisation (170 +/- 50 mn), infarct site and severity of cardiac failure. There was no significant difference in hospital mortality (7 in the rt PA group and 5 in the APSAC group) or in adverse effects (haemorrhage: rt PA: 9 patients, APSAC: 11 patients). The patency was 72% in the APSAC and 76% in the rt PA group. Left ventricular function and infarct size were comparable in the two groups: angiographic EF (0.50 +/- 0.1 in the APSAC and 0.52 +/- 0.1 in the rt PA group: NS); asynergic score (11.3 +/- 1.7 in the APSAC and 10.5 +/- 1.8 in the rt PA group: NS); infarct size (10.9 +/- 8.0 in the APSAC and 9.4 +/- 7.2 in the rt PA group: NS). This trial shows that these two thrombolytic agents have the same efficacy. The authors recommend adaptation of the dosage of rt PA to body weight. PMID- 1300958 TI - [Macrocreatine kinase, a cause of MB isoenzyme levels falsely elevated]. AB - The authors describe two cases of falsely elevated CPK-MB levels due to the presence of a Macro-CPK. The quantification of the mass of CPK-MB gave values lower than the cut-off level. Electrophoresis of CPK isoenzymes showed a type 1 Macro-CPK in one case and a type 2 Macro-CPK in the other. The authors recommend electrophoresis of CPK isoenzymes or quantification of mass if the clinical evolution or ECG changes do not correlate with the CPK-MB levels or if there is a low global CPK with high CPK-MB levels. PMID- 1300959 TI - [Ventricular tachycardia in a patient with rate-responsive cardiac pacemaker]. AB - The authors report a case of syncopal ventricular tachycardia in a patient with a respiratory-dependent rate responsive pacemaker, followed-up for valvular heart disease with severe left ventricular dysfunction and sustained atrial and ventricular arrhythmias. The introduction of low dose betablocker therapy with reinforcement of the treatment of cardiac failure controlled the ventricular arrhythmia, after suppression of the data responsive function had been shown to be ineffective. The authors discuss the role of the rate responsive function in the triggering of the ventricular tachycardias. PMID- 1300960 TI - [Fungal thrombus of the right atrium on a central venous catheter. Apropos of a case]. AB - The authors report the case of a 9 year old child in an intensive care unit after multiple trauma, presenting with a candida septicaemia and a central venous catheter. Echocardiography, performed because of the inefficacy of medical treatment, showed a right atrial thrombus. Surgical ablation was decided because of its extreme mobility and persisting infection, and resulted in cure of the patient. PMID- 1300962 TI - [Management and surgical treatment of malformations diagnosed in utero]. PMID- 1300961 TI - [Mycotic aneurysm of the carotid artery secondary to acute bacterial endocarditis]. AB - Mycotic aneurysms of the extracranial carotid arteries are rare. A new case of mycotic aneurysm of the bifurcation of the carotid artery secondary to acute bacterial endocarditis affecting the aortic valve is reported. Simultaneous treatment of the two lesions was instituted. The twenty six cases of mycotic aneurysm of the extracranial carotid arteries previously described in the literature are reviewed by the authors. PMID- 1300963 TI - [What is the future of congenital cardiopathies following surgical correction?]. PMID- 1300964 TI - [Intellectual development after relaxing the diet at the age of 5 years in typical phenylketonuria]. AB - BACKGROUND: No satisfactory controlled trial has yet been completed on typical phenylketonuria (PKU) patients whose treatment was relaxed at the age of 5 years. METHODS: 27 children having typical PKU were treated before the age of 3 months. The intake of phenylalanine and protein was carefully regulated during the first 5 years of life, after which the treatment was relaxed. All children were evaluated after at least 6 years on the relaxed diet. Their IQ scores and school performance were related to the degree of dietary control and plasma phenylalanine values. RESULTS: The IQ scores at 5 years of age were 100 +/- 10.8. Continued evaluation showed that IQ scores remained unchanged. Poor school performance was twice as frequent as in general population; the deficit in the IQ score of this group was 8 points below that of normal sibs. There was no correlation between plasma phenylalanine and the IQ score after the age of 5 years. The positive control decreased with aged. CONCLUSIONS: Children with typical PKU have an IQ deficit relative to their normal sibs just before relaxing treatment. Good dietary control until 5 years of age, maternal intelligence and continuing evaluation during relaxing diet are the best conditions for optimal intellectual progress. There is no evidence that continued treatment during adolescence is beneficial. PMID- 1300965 TI - [Pica and iron deficiency in adolescence]. AB - BACKGROUND: Pica is a habit disorder involving the compulsive, irrational ingestion of nutrient or non-nutrient substances which usually, in young infants, include clay and earth. Pica is rare in adolescents but is more likely to occur in subjects with severe iron deficiency. POPULATION AND METHODS: 17 (16 girls, 1 boy) cases of pica were recognized over a period of 4 years in an adolescent unit. 15 of the cases presented with anemia and/or iron deficiency. Hematological and biochemical investigations included measurements of hemoglobin content, MCV, serum iron and ferritin, transferrin saturation and serum iron-binding capacity. Blood loss was considered as a possible cause in all patients. RESULTS: 13 of the patients ingested large amounts of raw rice and 11 ingested ice cubes; 10 patients ingested both substances. Their mean serum ferritin was 7.17 ng/ml and the mean hemoglobin was 8.7 g/dl. One out of 7 patients showed intestinal blood loss. Excessive menstrual bleeding occurred in 8 girls. All patients were treated with adequate amounts of iron. Pica disappeared within a few weeks, although biochemical evidence of iron deficiency persisted in some patients. In one case, pica persisted despite correction of the iron deficiency. CONCLUSION: Pica is more prevalent in lower socio-economic classes and in some areas, such as the island of Reunion. It may be masked, and must be looked for in adolescents presenting with signs of iron deficiency. Treatment of the iron deficiency is usually followed by its disappearance. PMID- 1300966 TI - [Causes and modalities of pediatric ambulatory care in ten hospitals in the Ile de-France region]. AB - BACKGROUND: The increasing shortage of financial resources requires optimal use of hospital care by patients. However, the studies carried out to date in France have been limited to patients who are hospitalized, and have not included those seen as out-patients. POPULATION AND METHODS: All patients seen as out-patients in 10 hospitals in the Paris district (3 pediatric hospitals and 7 pediatric departments located in hospitals for adults and children), during the week of 19 26 April 1989, were given a questionnaire on the age, sex, nationality, socio cultural and economic features of the family, history of earlier medical visits or admissions, the existence of pediatrician or practitioner, and the means and time taken to get to the hospital. Medical diagnosis was established for each patient following the WHO International Classification of Diseases (9th edition). RESULTS: 2,365 out of 2,675 questionnaires were usable. The main features were: 50% of patients were less than 3 years old, 55% were of French origin; 78% belonged to families with relatively low socio-economic status. Both parents had professional activities in 49% of families, 7% of mothers did not speak or write French. The ratio of patients aged less than 3 years admitted to the emergency ward was higher than the average. The most frequent diseases presented by these patients were respiratory (23%), infectious (14%), gastro-intestinal (10%) and neurological (7%); 14% of the patients were seen for symptoms that could not be assigned to a specific disease. 39% of patients were seen in out-patient clinics and 61% in emergency wards. 40% were sent by a health professional to out-patient clinics and only 25% to emergency wards. CONCLUSIONS: Despite the fact that this study is subject to particular conditions, i.e., relative frequency of infectious diseases due to seasonal causes, it suggests that the hospital is becoming the primary source of health care with an increasing percentage of patients seen in "emergency", even though this emergency is often more apparent than real. Health care networks should be established. PMID- 1300967 TI - [Granulosa cell tumors of the ovary in children and adolescents. Multicenter retrospective study in 40 patients aged 7 months to 22 years]. AB - BACKGROUND: Juvenile granulosa cell tumors (JGCT) of the ovary are rare in children. The over-all outcome after surgery is relatively good, but the indication and type of complementary treatment for severe forms are still unclear. POPULATION: A retrospective survey of the majority of patients with JGCT of the ovary admitted between 1965 and 1990 to 11 French oncologic pediatric centers was carried out. Medical records including surgical and histological data, were analyzed and each tumor was retrospectively classified by the same pathologist according to the Wollner classification. RESULTS: There were 40 patients aged 7 months to 22 years (mean: 6 years); 28 were less than 10 year old at diagnosis. Three had enchondromatosis (Ollier's disease). At diagnosis, all patients presented with an abdominal tumor, 23 had developed manifestations of precocious pseudopuberty, 2 had signs of virilization after a normal puberty and 2 had secondary amenorrhea. Surgery was always the primary treatment: unilateral ovariectomy in 35 cases, bilateral in 4 and biopsy alone in 1 case. There were 21 stage I, 1 stage II, 16 stage III and 2 stage IV cases. 13 patients received combined chemotherapy and 2 abdominal radiotherapy. 34 patients were alive and disease-free 10 months to 26 years after surgery and 6 died. All 23 patients with precocious pseudopuberty had a favorable outcome. CONCLUSIONS: This study confirms earlier reports. Unilateral ovariectomy is the first-choice therapy. There is no evidence that tumors complicated by rupture and hemoperitoneum require chemotherapy. Combined chemotherapy does not appear to improve the prognosis for the rare malignant forms. The factors of good prognosis are age less than 10 years and the presence of precocious pseudopuberty. PMID- 1300968 TI - [Schwartz-Jampel syndrome (osteochondromuscular dystrophy)]. AB - BACKGROUND: Schwartz-Jampel syndrome is a rare disorder inherited as an autosomal recessive trait and characterized by growth retardation, multiple skeletal abnormalities, myotonia-like muscle disorders and unusual facies. CASE REPORTS: Case n. 1: A boy, aged 3 years 4 months, was admitted for acute respiratory disease. His main abnormalities included rigid facial expression, blepharophimosis, puckered lips, short neck, pectus carinatum, acetabular dysplasia with coxa vara, platyspondyly and marked growth retardation. There was a continuous muscle fiber activity at rest, with abnormal discharges originating in the muscle component of the neuromuscular junction. Blood investigations revealed low values of IgA. The child died at 4 years. Case n. 2: The sister of case n. 1 was examined at 14 months of age. She presented milder facies abnormalities, difficulties of gait because of stiff hips, muscular hypertrophy, coxa vara and growth retardation. X-rays showed skeletal abnormalities and the electromyogram was similar to those of her brother. She had dislocation of her optic lens. CONCLUSION: These 2 sibs have the characteristic manifestations of Schwartz-Jampel syndrome. Parental consanguinity was also present. The IgA deficiency observed in case n. 1 and the lens dislocation in case n. 2 have both been occasionally reported in this syndrome. PMID- 1300969 TI - [Continuous arteriovenous hemofiltration. Management in case of neonatal leucinosis]. AB - BACKGROUND: Neonates with classic maple syrup urine disease (MSUD) undergo rapid neurological deterioration by the end of the first week of life. Exchange transfusion and peritoneal dialysis are the usual emergency treatment. Continuous arteriovenous hemofiltration (CAVHF) appears to be safe and more rapidly effective. CASE REPORT: Martin was born at the 37th week from a normal pregnancy. Abnormal movements of legs and lethargy appeared on the 7th day of life. Progressive brain dysfunction with coma led to intubation on the 13th day. A diagnosis of MSUD was immediately made and CAVHF was initiated and continued for 19 hours. The plasma leucine, valine and isoleucine levels fell from 2,248 to 275, 640 to 91 and 298 to 13 mumol/l, respectively. Neurologic improvement was dramatic, except for moderate hypertonia which lasted for the 2 following days. CONCLUSION: CAVHF is an appropriate treatment for very young patients with inborn errors of metabolism. It appears safer and more rapidly effective for eliminating branched-chain amino acids than other techniques, such as peritoneal dialysis with or without exchange transfusions. It also permits more rapid introduction of the specific diet. PMID- 1300970 TI - [Mirror movements. Preliminary therapeutic study]. AB - BACKGROUND: Mirror movements are a specific type of synkinesis. The pathogenesis is unknown. Three types have been identified: 1) a hereditary form, 2) a form associated with other neurological diseases, 3) a sporadic form, as is this case. CASE REPORT: A girl was born at term after cesarean section for fetal anoxia. Psychomotor development seemed normal, but mirror movements of fingers, hands, wrists and forearms were noticed when she was 8-9 months old. There were no other neurological manifestations and the imaging techniques were normal. Rehabilitation was begun when she was 20 months old. The girl is now 4 1/2 years old and writes, draws and cuts up normally. CONCLUSIONS: Mirror movements that are not associated with other neurological disorders usually remain unchanged and can be a professional handicap for adults. Prolonged rehabilitation offers a good functional prognosis. PMID- 1300971 TI - [Medical treatment of chylous effusions in newborn infants. Apropos of 3 cases]. AB - BACKGROUND: Chylous effusions are the most frequent cause of non immunologic hydrops fetalis. They can be recognized antenatally by ultrasonography. Their evacuation is sometimes necessary and medical treatment often effective. CASE REPORTS: Case n. 1: fetal ascites was detected by ultrasonography at the 30th week of gestation. Paracentesis was performed at 36 weeks, followed 3 days later by spontaneous delivery. The newborn was fed milk formula. A second paracentesis showed a milky fluid, rich in cholesterol, triglycerides and chylomicrons. The child was fed formula rich in medium-chain triglycerides and the chylous ascites disappeared completely within 2 weeks. Case n. 2: a diagnosis of bilateral hydrothorax and hydramnios was made at the 27th week of gestation. An in utero evacuation of the hydrothorax performed at the 30th week was ineffective and a pleuro-amniotic drainage was performed 2 weeks later. The baby was born at the 35th week, and presented a moderate respiratory distress due to the hydrothorax and ascites. Aspiration of the thoracic fluid confirmed its chylous origin. The chylous effusions completely disappeared when the child was fed a high medium chain triglycerides diet. A lymphedema of legs appeared at the age of 1 month. Case n. 3: ascites, hydramnios, hydrothorax and peripheral edema were found at the 21st week of a third pregnancy (the 2 first pregnancies were complicated by lethal hydrops fetalis). Bilateral hydrothorax and peripheral edema were found again after birth at the 37th week. Diuresis and albumin-infusion led to recovery, but chylothorax and chylous ascites reaccumulated after introduction of milk formula, despite repeated evacuations and feeding medium-chain triglycerides formula. The thoracic fluid remains chylous at the age of 9 months. CONCLUSIONS: In utero, and sometimes post-natal, evacuation of fluid present in the thoracic and peritoneal cavities can be necessary, depending of the functional tolerance. Medical management including feeding a low fat and/or high medium-chain triglycerides diet, and sometimes temporary total parental nutrition, is necessary, together with salt restriction, diuresis and albumin infusion as required. Most cases recover spontaneously or as a result of therapy within a few weeks. PMID- 1300972 TI - [Phlebothrombosis revealing Behcet's disease in a 13-year-old adolescent]. AB - BACKGROUND: Behcet's disease is rare in children and is exceptionally revealed by thrombophlebitis at this age of life. CASE REPORT: A girl, aged 13 years, was admitted after having suffered from thrombophlebitis of the right leg for 6 weeks. Her medical history included frequent attacks of aphthous stomatitis and conjunctivitis and one episode of iritis. At admission, thrombophlebitis with venous thrombosis was confirmed by Doppler; it was associated with aphthous gingivitis and two similar erosive lesions in the genital area. Technetium 99 perfusion scintiphotography revealed a right pulmonary embolism. The erythrocyte sedimentation rate was elevated but there was no change in coagulation factors or immunologic abnormalities, except for the presence of immune complexes and increased complement C3 component. Biopsy of the skin lesions showed vascularitis. There was no involvement of the eyes. The condition progressively improved with anticoagulant treatment for 1 year, followed by low doses of acetylsalicylic acid. CONCLUSION: Phlebothrombosis, a classic complication of Behcet's disease in adults, revealed the disease in this girl. Its mechanism remains unclear and duration of anticoagulant treatment is still debated. PMID- 1300973 TI - [Iconographic rubric. Fatal gas embolism of pulmonary origin in a newborn infant with hyaline membrane disease]. PMID- 1300974 TI - [Use of furosemide in pediatrics]. PMID- 1300975 TI - [Syndromes of premature aging]. PMID- 1300977 TI - [Nocardial subphrenic abscess after splenectomy in a child with sickle cell thalassemia]. PMID- 1300976 TI - [Congenital toxoplasmosis at immediate or delayed serological disclosure in twins]. PMID- 1300978 TI - [Neonatal renal insufficiency secondary to niflumic acid administration in pregnancy]. PMID- 1300979 TI - [Secondary effect of fentanyl on the mechanical ventilation in premature infant]. PMID- 1300980 TI - [Gastroesophageal reflux in screening centers in children under 4 years of age]. PMID- 1300981 TI - Tissue distribution of MHC class II--positive cells, their down-manipulation by monoclonal antibodies and potential role in organ allograft immunogenicity. AB - This review article presents current state of knowledge of tissue distribution of MHC class II antigens in rat kidney. Our attention focuses particularly on down manipulation of these antigens by monoclonal antibodies. The results of organ perfusion procedure on prolongation of graft survival and perspectives of further studies are also discussed. PMID- 1300982 TI - Macrophage activating factors produced in the course of murine tularemia: effect on multiplication of microbes. AB - Primary F. tularensis infection in mice induces the production of macrophage activating factors (MAFs) by spleen cells. The stimulation of macrophage cytolytic activity (MAF-c) and hydrogen peroxide production (MAF-H2O2) dominates between days 7 and 10 in the course of tularemia. Three various pools of active fractions (10-11, 14-15, 25-28) were fractionated by two-step chromatography. Typical for 10-11 and 14-15 is MAF-c activity whereas in 25-28 prevails MAF-H2O2. Initial concentrated supernatant (day 7 of infection) and individual fractions have been used to raise antibodies KI (anti 10-11) and KII (anti 14-15). Neutralization reactions with specific antibodies indicate the presence of tumor necrosis factor alpha (TNF alpha) in 14-15 (44% inhibitable), interferon gamma (IFN gamma) and interleukin 2 (IL 2) in 25-28 (65% and 30% neutralization, respectively). Utilizing KI and KII, 99% and 90% inhibition of cytolytic activity is reached in 10-11 and 14-15, respectively, in spite of non-specific cross reaction. Western blot analysis of proteins in supernatant on day 7 detects, besides TNF alpha, further protein bands (13, 15.5, 52 and 72 kDa) that seem to be associated with macrophage activation. Significant protective effect against in vivo multiplication of tularemic microbes indicates a certain role of TNF alpha, however, cooperation of other molecules is worth to be taken into consideration. PMID- 1300983 TI - Two patterns of NK activity changes following blood donation: decrease in the beginners and restoration in regular blood bank donors. AB - NK cell activity of peripheral blood lymphocytes was determined in voluntary blood bank donors in a standard 4-hr 51Cr-release cytotoxicity assay. When blood donors were divided into groups according to the total amount of blood they had donated in the past, decreased NK activity was found in "moderate" donors who had donated between 3 and 9 l of blood, but not in those who had donated < or = 3 or more than 9 l of blood before testing. This observation was the rationale for a study on the effects of regular blood donations on NK activity in randomly selected voluntary blood bank donors re-tested over a period of time. The study demonstrated decreased NK activity in the second measurement in donors who had donated up to 6 l of blood before the study, and an increase in NK activity between the first and the second testing in those who had donated more than 6 l of blood. This result, together with data obtained at the population level, suggests that some compensatory mechanism(s) regulate NK activity in the course of regular blood donation. PMID- 1300984 TI - T lymphocyte subsets and NK cell cytotoxicity in chronic hemodialysis patients. The effect of recombinant human erythropoietin (rHu-EPO) treatment. AB - We investigated subpopulations of T lymphocytes, NK cell number and cytotoxic activity in 14 chronic uremic patients on regular hemodialysis treatment. We observed a significantly decreased absolute lymphocyte number and percentage of CD3 cells. Relative numbers of CD16 cells were significantly elevated, but NK cell cytotoxic activity was within a normal range. Nine patients with chronic renal anemia on maintenance hemodialysis were enrolled in rHu-EPO treatment trial. The treatment was continued till the hematocrit level reached 30%. Each of the patients had corrected anemia and well-being. After 12 weeks of the treatment we observed in these patients decreases in CD3, CD4, CD8 and CD16 cell numbers and elevation of CD4/CD8 ratio. Cytotoxic activity of NK cells did not change significantly. Presented results indicate that chronic hemodialysis patients have significantly diminished lymphocyte number. rHu EPO treatment affects the T lymphocyte subsets inducing a deep decrease of CD8 and CD16 cell percentage leading to normalisation of the CD4/CD8 ratio. PMID- 1300985 TI - The influence of tuftsin partial sequences on histamine level in guinea pig and rat tissues. AB - We investigated the influence of tuftsin partial sequences (Thr-Lys, Lys-Pro, Lys Pro-Arg and Pro-Arg) on histamine concentration in selected tissues (lungs, kidneys, liver, duodenal wall and arterial blood) of guinea-pigs and rats. The peptides were administered in 1 mg/kg dose intravenously (single dose) or intraperitoneally (single dose or three doses at one-hour intervals). Histamine concentration was determined spectrofluorimetrically. Tissues used in the determination were taken 1 hour after the last injection. It was found that Pro Arg and Lys-Pro-Arg (similarly to tuftsin), lower histamine concentration in lungs, and elevate it in kidneys. PMID- 1300986 TI - Immunosuppressive activity of tyrosine analogues of cyclolinopeptide A. AB - Immunosuppressive properties of six tyrosine analogues of cyclolinopeptide A were studied and compared with the activity of cyclosporin A. The peptides were investigated using PFC (in vitro) and DTH tests. PMID- 1300988 TI - Simultaneous induction of interferon gamma and tumor necrosis factor alpha by different seleno-organic compounds in human peripheral blood leukocytes. AB - Ebselen is known as anti-inflammatory and anti-oxidant selenium containing drug. We have synthetized 13 seleno-organic compounds, analogs of ebselen. Seven of them were found to be inducers of interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) in human peripheral blood leukocytes (PBL) cultures. The most active cytokine inducers were: 2-phenyl-1,2-benzisoselenazol 3(2H)-one (1, ebselen), bis [2-(N-phenylcarbamoyl)]phenyl diselenide (7) and bis (2-[N-(2-pyridyl)carbamoyl])phenyl diselenide (8). The amounts of IFN and TNF produced by PBL cultures in response to the seleno-organic compounds were found to be similar to that induced by phytohemagglutinin (PHA). The activities of the seleno-organic compounds were dose-dependent and related to the chemical structure of the drugs suggesting involvement of the specific cytokine-inducer receptor. The simultaneous inductions of IFN-gamma and TNF-alpha were highly correlated, but independent on each other. PMID- 1300987 TI - The activity of two immunotoxins composed of monoclonal antibody MoAb-16 and A chain of ricin (MoAb-16-RTA) or A-chain of mistletoe lectin I (MoAb-16-MLIA). AB - The A-chains of ricin obtained from Ricinus communis or mistletoe lectin I from Viscum album were coupled to the monoclonal, anti-L1210V antibody MoAb-16, using SPDP as a cross linking agent. The cytotoxic activity in vitro of these immunotoxins was compared. Each of two immunotoxins tested, applied in vitro for 1 h in appropriate doses, caused irreversible inhibition of leukemic L1210 cells proliferation. Unexpectedly, MoAb-16-MLIA immunotoxin appeared to be cytotoxic to normal bone marrow progenitor cells, as observed in NCFUS tests. Moreover, this immunotoxin revealed cytotoxic effect to the P388 leukemia cells which do not share the antigen, common within L1210 leukemia cells, detected by MoAb-16 antibody. PMID- 1300989 TI - Human lymphoid target cells for the cytokine-inducing seleno-organic compounds. AB - Several seleno-organic compounds including ebselen are known as antiinflammatory and antioxidant agents. They also have glutathione peroxidase-like activity and are inhibitors of leukotrienes and prostaglandins. We have recently discovered that these drugs are inducers of cytokines, mainly interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and mitogenic interleukins in human peripheral blood leukocytes (PBL) but not in the mouse or rat lymphoid cells. We described a production of IFN-gamma and TNF-alpha by various subsets of PBL stimulated with 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) or bis [2-(N phenyl-carbamoyl)]phenyl diselenide. IFN-gamma was produced mainly by E-rosette positive lymphocytes. However, the presence of monocytes was required for the optimal production of IFN-gamma. Also soluble mediators released by monocytes enhanced IFN-gamma synthesis. On the other hand, TNF-alpha was produced mainly by the adherent monocytes. Its synthesis was enhanced by the addition of T or B lymphocytes or conditioned medium from the culture of the stimulated lymphocytes. The relative concentrations of the subsets of lymphocytes or monocytes was important for the maximum production of both IFN-gamma and TNF-alpha. High concentration of lymphocytes inhibited the cytokine production. PMID- 1300991 TI - Dentofacial orthopaedic correction of maxillary retrusion with the protraction facemask--a literature review. AB - The retruded maxilla in the Class III skeletal pattern could be effectively corrected with the protraction facemask in selected cases. A review of the different types of orthopaedic appliances used in Class III treatment, the rationale for facemask therapy, the effect of this treatment and the factors affecting stability is presented. PMID- 1300990 TI - The association between occlusion and attrition. AB - The purpose of this study was to identify variables of malocclusion that might be associated with attrition and then to quantify the relationship between these variables and attrition. The results of this study indicate that, with all other factors held constant, a patient's attrition score tends to: increase with age, increase with bite depth, decrease initially with overjet until a critical value and then increase, and be unaffected by sex, interincisal angle, U1 to NA angle, Angle classification, posterior or anterior cross bites. Further, we discuss the statistical treatment of data of this kind and emphasize the importance of a professional approach to analysis. PMID- 1300992 TI - A novel method of sterilizing orthodontic instruments. AB - A range of orthodontic instruments was artificially inoculated with a mixed culture of representatives of the oral microflora and a marker bacterium and subjected to dry heat sterilization using a glass bead sterilizer. The shortest time which would guarantee total sterilization of the functional parts of the instruments was thirty seconds. PMID- 1300993 TI - A new concept in the Begg technique: the separate arch system. AB - The author reports on the Separate Arch System (SAS) he has devised by adapting basic Begg Technique concepts in the light of his clinical experiences. SAS, a multi-bracket arrangement using reverse light wire brackets, is a method of initiating orthodontic movement in the anterior and posterior segments separately, but completing them at the same time. The method's features include: a) use of thinner wire in segments and in multiple strands, as needed, maximising benefits of light force and differential anchorage; b) one-point rigidity in the wire-bracket relation; c) the method can be applied in both extraction and non extraction cases; d) the patient's home care is simplified; e) the method is quick, simple, and systematic (thus making estimation of a therapy goal possible). PMID- 1300994 TI - A procedure for attachment of gold chain for traction of impacted teeth. AB - There is a need to improve the strength of the attachment of the gold chain to impacted teeth. Dislodgement of the gold chain requires a second surgery for reattachment. Failures have been observed to occur at two interfaces. The authors have devised a method of attaching the gold chain to the mesh pad securely, by ligating them together. This article describes the method and discusses other factors which enhance the retention of the gold chain to the impacted tooth. PMID- 1300995 TI - Case report--swallowed piece of archwire. AB - A fifteen year old healthy, male patient contacted our office stating that whilst eating a bread roll he had swallowed a piece of orthodontic archwire. He complained of stomach pain and was advised to contact his local medical practitioner who had the area radiographed. The radiographic examination revealed the piece of archwire to be lodged in the pylorus. The patient was then referred to a consultant physician who, using a gastroscope and with the orthodontist present, to assist with supervision of the orthodontic appliance during gastroscopy and to determine that the piece removed had not undergone further fracture, removed the piece of broken archwire. The piece of wire was forwarded to the Therapeutic Devices Branch of the Department of Community Services and Health for analysis. PMID- 1300996 TI - [Hidden symmetry of peptide and protein primary structures]. AB - The internal symmetry of peptide chains was considered. To identify symmetrically located equivalent amino acids, the signatures method and the code of amino acid codon roots were applied. There was revealed the hidden symmetry of amino acid sequences of peptides and proteins as well as of their active centres. Amino acids having common codon roots in primary (and supposedly in the spatial "biologically active") molecular structures, are located symmetrically. Definition of local symmetry of peptide chains was proposed to use as one of the elements of complex analysis to determine location of molecular active centres. PMID- 1300997 TI - [Approach to studying the structure-activity relationship of native peptides. I. Structural organization of the opioid peptide Tyr-Glu-Gly-Phe-Met-Arg-Gly-Leu and its artificial analogs]. AB - Theoretical conformational analysis was carried out for the octapeptide Tyr1-Gly2 Gly3-Phe4-Met5-Arg6-Gly7-Leu8. Possible structure of the opioid peptide under physiological conditions may be described by a set of low-energy conformations belonging to 14 different forms of the backbone. The solution of the "reverse conformational problem" for the opioid peptide enables one to predict the modified amino acid sequences (Ala2, D-Ala2, Ala3, D-Ala3, Ala7, D-Ala7, MeMet5, MeArg6-analogues) which may assume one of the low-energy states of the native hormone. The influence of the solute was not taken into account in our calculations. PMID- 1300998 TI - [Approach to studying the structure-activity relationship of native peptides. II. Structural organization of alpha- and beta-neoendorphins]. AB - By means of a semi-empirical method, an a priori conformational analysis of alpha and beta-neo-endorphins was carried out. Calculations yielded the values of all dihedral angles of the backbone and side chains of the peptide's various forms as well as intra- and inter-residue interaction energies. PMID- 1300999 TI - [BspLS2I--a new site-specific endonuclease from the thermophilic bacteria Bacillus species LS2]. AB - A new restriction endonuclease BspLS2I was isolated from the thermophilic bacterium Bacillus species LS2 and purified by blue sepharose and hydroxyapatite chromatographies. The enzyme is an isoschizomer of SduI from Streptococcus durans. BspLS2I recognizes the sequence 5' G(G/A/T)GC(C/T/A) decreases C 3' on double-stranded DNA and cleaves it is indicated by the arrow to yield sticky ended DNA fragments. Maximum catalytic activity of endonuclease was found in 10 mM tris-HCl (pH 7.9) in the presence of 15-30 mM MgCl2 at 50 degrees C. The phage T4 glucosylated DNA is not cleaved by the enzyme. PMID- 1301000 TI - [Genetically engineered human insulin. 1. HPLC in analyzing products of basic production stages]. AB - Application of some variants of HPLC for the step-by-step analysis of recombinant human insulin production was studied. Chromatographic columns with commercial and specially developed supports for size-exclusion, ion-exchange and reverse phase HPLC were used. Effective combinations of the chromatographic techniques for analysis of products and intermediates at every technological step were found and used for production of insulin. The authenticity of insulin obtained in the Shemyakin Institute of Bio-organic Chemistry by the scheme described in the present paper was confirmed by means of some physical and chemical methods and biological activity analysis. PMID- 1301001 TI - [Chemical-enzymatic synthesis and cloning of the full-length genome of a DNA containing plant virus]. AB - The full-length genomic DNA of a small plant virus--coconut foliar decay virus (CFDV)--has been synthesized by a combination of chemical synthesis, ligation and polymerase chain reaction. Three separately cloned DNA fragments of the genomic DNA were sequenced and assembled in the pPCV002 plasmid vector. PMID- 1301002 TI - [Structure of a single-stranded DNA target as a factor influencing the effectiveness of its modification with a complementary reagent]. AB - Site directed alkylation of three oligonucleotide targets: 41-mer (hairpin structure), 22-mer (loop part of this hairpin) and 10-mer (part of the loop) with 5'-p-(N-2-chloroethyl-N-methylamino)benzylamides of oligonucleotides complementary to the loop region was studied. Thermodynamic parameters of the interaction were estimated using the dependence of the limit modification extent on the reagent concentration at different temperatures. The stability of the complex increases much in the set: 302-mer carrying the above hairpin, 41-mer, 22 mer; data on 22-mer and 10-mer being almost identical. This indicates significant influence of the loop supporting structure on the interaction with antisense reagents. PMID- 1301003 TI - [Structure of the polysaccharide component of the bioglycan from the sea scallop Patinopecten uessoensis]. AB - A bioglycan, [alpha]20D + 144 degrees (c 0.7, water), was isolated from the mantle of the scallop Patinopecten yessoensis, which is widespread in the Sea of Japan. The bioglycan represents a complex of alpha-D-glucan (83%) and protein (13%) and was homogeneous as judged by gel-filtration and ultracentrifugation. By means of molecular-sieve chromatography on Sepharose CL-4B, its average molecular weight was estimated as 4 MDa. Methylation studies, periodate oxidation and amylolysis showed that the polysaccharide part of the bioglycan consisted of alpha-1,4-linked D-glucopyranose residues, with side chains attached to every fourth sugar unit of the backbone through alpha-1,6-linkages (some side chains seem to be 1,3-linked). The structure of the bioglycan was confirmed by NMR spectral data. Amino acid composition of the protein part of the bioglycan was elucidated. The scallop bioglycan is related to the known bioglycans immunomodulators of marine invertebrates with regard to the structure and immunological behaviour. PMID- 1301004 TI - [Mechanism of action of vitamin E. Study of the interaction of vitamin E (alpha tocopherol) and its analogs with fatty acids and their derivatives by fluorimetry]. AB - Formation of a complex between alpha-tocopherol or its analogues in the excited state and fatty acids or their hydroperoxides has been suggested basing on the fluorescence quenching experimental data. The possible mechanism of the complex formation, its nature and role in the fatty acid peroxidation is discussed. PMID- 1301005 TI - [Photosystem II of rye. Nucleotide sequence of the psbK gene and regions adjacent to it]. AB - The structure of the rye chloroplast DNA which contains the psbK gene coding for a subunit of photosystem II is determined. The gene psbI encoding an other protein of photosystem II is located 407 bp downstream from the stop codon of this gene. The determination of structure of the intergenic region between the psbI and psbD genes is fully elucidated. The rye BamHI fragment, comprising the psbK gene, is structurally similar to the corresponding fragment of the barley genome. PMID- 1301007 TI - Transport parameter estimation from lymph measurements and the Patlak equation. AB - Two methods of estimating protein transport parameters for plasma-to-lymph transport data are presented. Both use IBM-compatible computers to obtain least squares parameters for the solvent drag reflection coefficient and the permeability-surface area product using the Patlak equation. A matrix search approach is described, and the speed and convenience of this are compared with a commercially available gradient method. The results from both of these methods were different from those of a method reported by Reed, Townsley, and Taylor [Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1037-H1041, 1989]. It is shown that the Reed et al. method contains a systematic error. It is also shown that diffusion always plays an important role for transmembrane transport at the exit end of a membrane channel under all conditions of lymph flow rate and that the statement that diffusion becomes zero at high lymph flow rate depends on a mathematical definition of diffusion. PMID- 1301006 TI - Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term. AB - OBJECTIVE: The purpose of this study was to determine the frequency, microbiologic characteristics, and clinical significance of microbial invasion of the amniotic cavity in women with premature rupture of membranes at term. STUDY DESIGN: Amniocentesis was performed in 32 women with term premature rupture of membranes and amniotic fluid cultured for aerobic and anaerobic bacteria and Mycoplasmas. RESULTS: The prevalence of positive amniotic fluid cultures was 34.3% (11/32). The most common isolates were Ureaplasma urealyticum, Peptostreptococcus sp., Lactobacillus sp., Bacteroides fragilis, and Fusobacterium sp. Clinical chorioamnionitis occurred only in one patient with a positive amniotic fluid culture. Her neonate had ophthalmitis. Three patients (9.4%) had endometritis. Among women who were delivered vaginally, those with a positive amniotic fluid culture had a significantly higher rate of endometritis than those with a negative culture (33% [3/9] vs 0% [0/20], respectively, p = 0.023). CONCLUSIONS: These data indicate that microbial invasion of the amniotic cavity occurs in approximately one third of patients with preterm premature rupture of membranes. Microbial invasion of the amniotic cavity is a risk factor for endometritis in women with term premature rupture of membranes. PMID- 1301008 TI - Prospective assessment of biofeedback for the treatment of paradoxical puborectalis contraction. AB - Eighteen patients with chronic constipation were diagnosed as having paradoxical puborectalis contraction (PPC) as the cause for their constipation. The diagnosis of PPC was made after office evaluation, colonic transit study, manometry, cinedefecography, and electromyography (EMG). These 18 patients had a mean duration of symptoms of 26.9 years; none of these patients had unassisted bowel movements. Fourteen patients had a mean of 4.6 laxative-induced bowel evacuations per week, and 11 patients had a mean of 4.4 enema-induced bowel evacuations per week. Patients underwent a mean of 8.9 one-hour EMG-based biofeedback sessions. At a mean follow-up of 9.1 (range, 0.5-12) months, these 18 patients had a mean of 7.3 unassisted bowel actions per week (P less than 0.0001). In addition, persistent laxative use was reported by only two patients, and, in both cases, this was once a week or less (P less than 0.001). Similarly, enema use was reported by only three patients, one once weekly and the other two thrice weekly (P less than 0.002). No biofeedback-related complications were identified. EMG based biofeedback is a valuable technique associated with an 89 percent success rate in the treatment of PPC. PMID- 1301009 TI - Prevention and early detection of colorectal cancer. AB - Adherence to a low-fat, high-fiber diet and regular screening to detect and identify polyps at an early, more treatable stage may reduce deaths from colorectal cancer. Patients should be told that they can reduce their risk of colorectal cancer by increasing their intake of fruits, vegetables and whole grain cereals and decreasing their intake of fat. Although scientific controversy exists regarding the specific methods and intervals of screening for colorectal cancer, family physicians should adopt a regular approach to screening in their patients. In adults 50 years of age or older, annual fecal occult blood testing is recommended. If positive results are obtained, follow-up examination should be performed with either colonoscopy or flexible sigmoidoscopy plus air-contrast barium enema. Persons between 50 and 75 years of age may also benefit from screening with flexible fiberoptic sigmoidoscopic examination every three to five years. PMID- 1301010 TI - Long-range correlations in nucleotide sequences. AB - DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes. PMID- 1301011 TI - Preparing patients for tube feeding at home. PMID- 1301012 TI - Venous thromboembolism in stroke: literature review and implications for clinical practice. PMID- 1301013 TI - Seizures in a patient treated with continuous povidone-iodine mediastinal irrigation. PMID- 1301014 TI - Is tomography of intervertebral disc calcification useful in children? AB - In the past ten years, we have found cervical intervertebral disc calcifications in three children on plain films of the cervical spine made because of cervical pain. In each case, we required further radiological investigations, antero posterior and lateral linear tomography for two children and an axial computed tomography for one child. In each case, tomography revealed no supplementary useful information. On retrospect, we think that these examinations caused unnecessary irradiation and that they should only be carried out in the rare circumstances when disc calcification is associated with neurological symptoms. PMID- 1301015 TI - Quinolone resistance: an alternative perspective. PMID- 1301016 TI - India's physicians debate whether to go abroad or go private. PMID- 1301017 TI - Partial ileal bypass in the treatment of hypercholesterolemia. AB - Partial ileal bypass is a surgical method of lowering circulating cholesterol levels. This article outlines the history of the partial ileal bypass operation and compares the efficacy, durability, compliance, safety, and cost of this operation with currently available diet and drug therapy for hypercholesterolemia. Partial ileal bypass patients have been followed for up to 26 years, and the procedure is employed currently throughout the United States and Europe. Partial ileal bypass has moved beyond the research stage and can be performed in community hospitals by competent general surgeons. PMID- 1301018 TI - Malignant angioendotheliomatosis (intravascular lymphomatosis) clinically simulating primary angiitis of the central nervous system. AB - Primary angiitis of the central nervous system (PACNS) and malignant angioendotheliomatosis (MAE) are two unrelated and lethal diseases that frequently affect the brain. Both are uncommon and both require histologic documentation of their characteristic lesions for a definitive diagnosis. Because brain biopsies are not routinely included in the diagnostic workup of non neoplastic CNS diseases, a number of unconfirmed nonvasculitic conditions may mimic PACNS. To my knowledge, MAE simulating PACNS clinically and angiographically has not been previously reported, and 3 such cases are described herein. PMID- 1301019 TI - Second license for the advanced practice nurse? PMID- 1301020 TI - Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor. AB - A pathological hallmark of Alzheimer's disease is the deposition of amyloid fibrils in the brain. The principal component of amyloid fibrils is beta/A4 amyloid protein, which can be generated by the aberrant processing of a large membrane-bound glycoprotein, the beta/A4 amyloid protein precursor (APP)3. To test whether overexpression of APP generates abnormally processed derivatives that affect the viability of neurons, we stably transfected full-length human APP complementary DNA into murine embryonal carcinoma P19 cells. These cells differentiate into post-mitotic neurons and astrocytes after exposure to retinoic acid. When differentiation of the APP cDNA-transfected P19 cells was induced, all neurons showed severe degenerative changes and disappeared within a few days. The degenerating neurons contained large amounts of APP derivatives that were truncated at the amino terminus and encompassed the entire beta/A4 domain. These results suggest that post-mitotic neurons are vulnerable to overexpressed APP, which undergoes aberrant processing to generate potentially amyloidogenic fragments. PMID- 1301022 TI - Mass media for health promotion: health Leninists or change agents? PMID- 1301021 TI - Radiotherapy and ophthalmology: time for a friendly re-acquaintance. PMID- 1301023 TI - Corticosteroid induced osteoporosis in severe menstrual asthma. Steroid sparing drugs may be useful. PMID- 1301024 TI - Men account for a scant 3% of all nurses. PMID- 1301025 TI - Readers advocate pro-conscience, not pro-choice. PMID- 1301026 TI - Folic acid. Agencies split on nutrition advice. PMID- 1301027 TI - Effect of constituents of burned skin and in vivo skin burning on the respiratory activity of rat liver mitochondria. AB - The formation of toxic substances in the skin, due to the influence of thermal energy, is supposed to be one possible mechanism responsible for the high mortality rate after severe burns covering large areas of the body surface. The effects of low-molecular-weight volatile substances (dry distillates) generated after burning mouse skin were investigated. They led to reductions of the respiratory activity of rat liver mitochondria. Among other substances carbon disulphide, methylethylketone and pyrrole were isolated and characterized using gas chromatography. All of them had strong uncoupling effects on mitochondrial respiration. In a second study respiratory measurements were made on mitochondria from rats with 20-30 per cent TBSA full skin thickness burns. A decreased respiratory control ratio and thus uncoupling of mitochondrial respiration was found on days 1, 2 and 5 postburn. The basal mitochondrial respiration was significantly decreased on day 5, which could be important for the mortality mentioned above. Finally after cross-transplantations rats having burned skin grafted showed a reduction of the RCR when compared with rats with the unburned graft. Thus it can be concluded that toxic substances must have been present in burned skin. PMID- 1301028 TI - Drugs and the exercise test. PMID- 1301029 TI - Oestrogen replacement therapy after hysterectomy. AB - OBJECTIVE: To identify those women who might benefit from oestrogen replacement after hysterectomy. DESIGN: Targeted health screening. SETTING: Large group practice. SUBJECTS: All women aged under 50 who had had a hysterectomy. MAIN OUTCOME MEASURES: Concentration of follicle stimulating hormone, symptom profile, uptake of oestrogen replacement therapy. RESULTS: 145 of 1953 women aged 32-49 had had a hysterectomy. 35 of the 41 with bilateral oophorectomy and 27 of 104 with one or more ovaries conserved were taking oestrogen replacement. 62 of the 68 who had ovaries conserved and were not taking oestrogen replacement attended for review, of whom 14 had a follicle stimulating hormone concentration > or = 20 IU/l. 16 of the 19 women identified as potentially able to benefit from oestrogen replacement started treatment and were still on treatment at six months of follow up. CONCLUSION: Systematic review of women who had had a hysterectomy identified an important group who would potentially benefit from oestrogen replacement therapy. PMID- 1301031 TI - Patient triggered synchronized assisted ventilation of newborns. PMID- 1301030 TI - An alternative to QALYs: the saved young life equivalent (SAVE) PMID- 1301032 TI - Another taboo bites the dust. AB - Squeamishness has too often in the recent past inhibited sensible inquiries into the mechanisms by which AIDS is spread through human populations but now there may be proof that these attitudes are changing. PMID- 1301033 TI - The role of exocytosis in the apocrine secretion of milk lipid globules in mouse mammary gland during lactogenesis. AB - Functional relations between exocytotic vesicle membranes, plasmalemma and milk fat globule membranes (MFGM) were studied during the final stages of mouse mammary gland differentiation, in the gland during full lactation and in the postpartum gland in which the synthesis of secretory products was partly inhibited by application of 2-Br-alpha-ergocryptine. Analysis of ultrathin sections, freeze-fracture replicas, scanning electron microscopy and application of a cytochemical marker filipin showed that the apocrine secretion of lipid globules was closely related to the exocytosis of milk proteins. During the last days of gestation the secretion of lipid globules resulted from many exocytotic events of the secretory vesicles that accumulated and fused around the cytoplasmic lipid droplets. Seldom the lipid droplet protruded partly into the gland lumen and a part of its surface became covered with the apical plasmalemma. Although apical plasmalemma became more important in the formation of MFGM in the postpartum period, we could still confirm a direct contribution of secretory vesicle membranes to the final detachment of the lipid globule. The application of 2-Br-alpha-ergocryptine hindered the apocrine secretion of the lipid globules and a situation similar to the situation in the prepartum gland was observed. PMID- 1301034 TI - Comments on the article 'Radiotherapy of metastatic spinal cord compression' by B. Jeremic et al. in Acta Oncologica 1991; 30: 985-6. PMID- 1301035 TI - Practical considerations of melanoma/skin cancer screening clinics. PMID- 1301036 TI - Serotonin, gastric emptying, and dyspepsia. PMID- 1301037 TI - Pneumocystosis in patients with acquired immunodeficiency syndrome. AB - Nurses need to be aware that pneumocystosis is one of the most common and lethal opportunistic infections among AIDS patients. They are extremely susceptible because HIV impairs physiological mechanisms for microbial defense. Patients exhibit only minor symptomatology while the unchecked P carinii organisms accumulate and replicate. Eventually as the sporozoans create a physical barrier between the alveolar-capillary membranes, ventilation becomes impaired and severe hypoxemia develops. Early clinical and diagnostic studies mimic the findings characteristic of ARDS. Unless correct staining techniques are used on sputum specimens, the organism often escapes identification. Thus, the diagnosis and specific treatment of PCP is often delayed. While supporting ventilation, the treatment of choice is administration of antimetabolite drugs, either trimethoprim-sulfame-thoxazole or pentamidine isethionate. The search for more effective, as well as safer, treatment of PCP continues. Life-threatening nursing diagnoses such as impaired gas exchange urgently require priority attention. Besides physical care, the severe hypoxemia demands nursing approaches to help the critically ill patient deal with fear and powerlessness. The nurse also assumes a surrogate role to patients abandoned by family and friends. The psychosocial aspects of nursing care require enormous skill and finesse, because the blood and respiratory isolation precautions can communicate mixed messages to lonely, frightened patients. PMID- 1301038 TI - Therapeutic levels of recombinant hirudin. PMID- 1301039 TI - Follicular keratosis of the chin. PMID- 1301040 TI - Gastrointestinal endoscopy. PMID- 1301041 TI - Quality assurance and total quality management. PMID- 1301042 TI - Deterioration on the Blessed Information-Memory-Concentration Test in Alzheimer's disease. PMID- 1301043 TI - Control of measles in New South Wales. PMID- 1301044 TI - Drugs and the exercise test. PMID- 1301045 TI - Clozapine. PMID- 1301046 TI - Achieving quality of care. PMID- 1301047 TI - Normalization--still relevant today. PMID- 1301048 TI - 'Important facts in the diagnosis of diabetes mellitus'. PMID- 1301049 TI - Mitral valve prolapse syndrome (MVPS) and associated thoracic skeletal abnormalities. PMID- 1301050 TI - More about avulsed primary teeth. PMID- 1301051 TI - Prevention of infective endocarditis. PMID- 1301052 TI - Recommendations for pacing. PMID- 1301053 TI - Patient compliance. PMID- 1301054 TI - Sexually transmitted diseases and anal papillomas. PMID- 1301055 TI - Dosimetric accuracy at low monitor unit settings. PMID- 1301056 TI - Ultrasonic detection of parathyroid adenomas. PMID- 1301057 TI - Mesosigmoplasty as a definitive operation for sigmoid volvulus. PMID- 1301058 TI - Antibodies to sulfur mustard. PMID- 1301059 TI - Nil by mouth after midnight? PMID- 1301060 TI - Effect of infusion rates on toxicity of amphotericin B. PMID- 1301061 TI - Oxygenation of partially oxidized human hemoglobin. PMID- 1301062 TI - Cellular localization of Nef expressed in persistently HIV-1-infected low producer astrocytes. AB - OBJECTIVES: The characterization and localization of HIV-1 Nef highly expressed in permanently infected astrocytes (TH4-7-5) as a model for latent infection of human brain cells. DESIGN: Immunochemical methods are an appropriate tool to investigate expression and localization of cellular proteins. METHODS: Nef expression was analysed by Western blot and immunoperoxidase staining using a panel of monoclonal and polyclonal antibodies. Cellular localization studies were performed by indirect immunofluorescence and subcellular fractionation of TH4-7-5 cells. Myristoylation of Nef was investigated by immunoprecipitation of [3H]myristic acid-labelled cell extract. TH4-7-5 nef gene was cloned and amplified by polymerase chain reaction and the nef nucleotide sequence analysed. RESULTS: Reactivities of various Nef-specific antibodies with Nef antigen in TH4 7-5 cells were demonstrated by Western blot analysis. Immunofluorescence revealed cytoplasmic perinuclear staining of Nef with most antibodies. However, one monoclonal antibody against amino acids 168-175 of Nef showed intense homogeneous nuclear staining in TH4-7-5 cells. Reactivity of this Nef antibody was blocked with recombinant Nef derived from TH4-7-5 cells. After subcellular fractionation, Nef was detected in nuclear, membrane and cytosolic fractions of TH4-7-5 cells. No myristoylated Nef antigen was detectable, perhaps because of a serine residue at position 2 of the TH4-7-5 nef gene instead of the glycine residue required for myristoylation. CONCLUSIONS: Chronically HIV-1-infected astrocytoma cells with restricted virus production express different antigenic forms of Nef, which can be distinguished by their subcellular localization. Variant subcellular targeting of Nef suggests the existence of multiple activities of Nef within HIV-infected cells. PMID- 1301063 TI - Nonhuman primates hold clues to search for AIDS vaccine. PMID- 1301064 TI - A sensitive competitive ELISA for 2,4-dinitrophenol using 3,6-fluorescein diphosphate as a fluorogenic substrate. AB - A competitive ELISA for sensitive detection of 2,4-dinitrophenol (DNP) was established. Certain amounts of bovine serum albumin conjugate of DNP were readily coated on a polystyrene microplate. Free DNP was then quantitated by its competition with the coated DNP for binding to anti-DNP (antibody)-alkaline phosphatase conjugate. The enzyme conjugate remaining on the plate surface as a result of the competition was detected by an enzymatic reaction with a fluorogenic substrate, 3,6-fluorescein diphosphate (FDP), or comparatively with a conventional chromogenic substrate, p-nitrophenyl phosphate (PNPP). The results showed that the ELISA with FDP at the optimal conditions of enzymatic reaction can detect as little as 10 fmol DNP, a detection limit of 50 times less than that with PNPP. The easy and sensitive DNP assay procedures in this work can be generalized to ELISAs for other antigens, particularly small antigens, haptens or drugs. PMID- 1301065 TI - Structure of (E)-5-(methoxymethylene)-2,4-imidazolidinedione. AB - C5H6N2O3, Mr = 142.11, monoclinic, P2(1)/n, a = 3.862 (1), b = 16.329 (2), c = 10.088 (1) A, beta = 98.77 (2) degrees, V = 628.7 (2) A3, Z = 4, Dx = 1.50 g cm 3, lambda(Mo K alpha) = 0.71069 A, mu = 1.18 cm-1, F(000) = 296, T = 296 K, R = 0.035 for 1124 independent reflections with I greater than 3 sigma(I). The structure is a hydantoin derivative with a methoxymethylene group substituted at the 5-position. Excluding the H atoms, the molecule is planar to within 0.032 A. All of the N and O atoms are involved in an intermolecular hydrogen-bonding network via N--H...O and C--H...O interactions. The packing arrangement is a linear ribbon motif with the ribbons stacked to form the short a axis. PMID- 1301066 TI - Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning. AB - BACKGROUND: Several recent studies suggest that activation of ATP-dependent potassium (K(ATP)) channels in the myocardium plays an important cardioprotective role during ischemia. The present study was undertaken to examine further the role of this ion channel in vivo in a model of "stunned" myocardium. METHODS AND RESULTS: Barbital-anesthetized dogs were subjected to 15 minutes of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. Regional myocardial blood flow was measured by radioactive microspheres and segment function by sonomicrometry. Intravenous administration of the potassium channel opener aprikalim (RP 52891) at a dose that produced no significant systemic hemodynamic effects (10 micrograms/kg plus 0.1 microgram/kg/min) resulted in a marked improvement in segment shortening in the ischemic/reperfused myocardium compared with control animals (p less than 0.05) when given before the ischemic insult. However, administration of aprikalim immediately before reperfusion had no beneficial effect. Furthermore, pretreatment with the K(ATP) channel antagonist glibenclamide antagonized the recovery of contractile function afforded by aprikalim when administered at a low dose (0.3 mg/kg) that alone had no effect on postischemic recovery. In contrast, pretreatment with either a higher dose of glibenclamide (1.0 mg/kg) or the related sulfonylurea K(ATP) channel antagonist tolbutamide (100 mg/kg) resulted in a worsening of segment function after reperfusion. The ability of aprikalim and the K(ATP) channel antagonists to alter postischemic wall function occurred independently of differences in systemic hemodynamics, area at risk, and collateral blood flow during occlusion, the major determinants of the extent of myocardial stunning. CONCLUSIONS: These results suggest that opening myocardial K(ATP) channels in the ischemic heart results in a marked cardioprotective effect in stunned myocardium and that these channels may serve an endogenous function, which is to provide protection from ischemic insults. PMID- 1301067 TI - Synthesis of serine-AMC-carbamate: a fluorogenic tryptophanase substrate. AB - A new fluorogenic substrate for the pyridoxal 5'-phosphate-dependent enzyme tryptophanase is described. L-Serine, which is linked to 7-amino-4-methylcoumarin through an O-carbamoyl tether, serves as a substrate for the enzyme. The released moiety, 7-amino-4-methylcoumarin (AMC), can be detected by either absorbance (355 nm) or fluorescence (excitation 365 nm/emission 440 nm). Kinetic constants were measured using each of these techniques: Km = 85 +/- 20 microM, Vmax = 2.9 +/- 0.4 mumol/min/mg (fluorescence) and Km = 129 +/- 21 microM, Vmax = 3.1 +/- 0.3 mumol/min/mg (absorbance). The Vmax for serine-AMC-carbamate is approximately 1.9 times faster than that of the natural substrate, tryptophan. Using fluorescence detection, solutions containing 10(-3) units of activity could be routinely assayed. PMID- 1301068 TI - Effects of oxidizing and reducing analogs of acetylcholine on neuronal nicotinic receptors. AB - The synthesis and pharmacological characterization of dithiobisacetylcholine and dithiobis-N,N-dimethyl-4-acetylpiperazinium (two oxidizing analogs of acetylcholine), as well as those of their reduced counterparts, are described. Both the oxidizing and reducing analogs stimulate nicotinic receptors in the chick retina and block the binding of 125I-labeled neuronal bungarotoxin to retinal homogenates (IC50 values of 2 x 10(-6) to 6 x 10(-5) M). Both oxidizing compounds reverse the physiological effects of reduction by dithiothreitol on nicotinic function in intact chick retina, when applied for 2 sec (EC50 values of about 10(-5) M). This effect is selective, insofar as neither agent alters the effects of dithiothreitol treatment on receptors for N-methyl-D-aspartate. Reoxidation takes place at the disulfide located near the nicotinic receptor agonist binding site, inasmuch as reoxidation by these agents prevents affinity alkylation by bromoacetylcholine, and occupation by the competitive antagonist d tubocurarine prevents reoxidation. Unlike thiocholine, a weak agonist with a free sulfhydryl that, paradoxically, is reported to oxidize nicotinic receptors in electroplax, the reduced forms, mercaptoacetylcholine and N,N-dimethylamino-4 mercaptoacetylpiperazinium, have no direct redox effects on retinal receptors, but they do protect the receptors against reduction by dithiothreitol. PMID- 1301069 TI - Inactivation of new carbapenem antibiotics by dehydropeptidase-I from porcine and human renal cortex. AB - The stability of the new carbapenem antibiotics, panipenem, meropenem and LJC 10,627, against porcine and human renal dehydropeptidase-I (DHP-I) was compared with that of imipenem. The order of stability to hydrolysis by renal DHP-I was: LJC 10,627 greater than meropenem greater than panipenem greater than imipenem. After incubation of the drugs with porcine or human enzyme at 30 degrees C for 4 h, the percentages of residual activity were as follows: LJC 10,627, 73.7% and 95.6%, respectively; meropenem, 0.2% and 28.7%, respectively; panipenem, 0% and 4.3%, respectively; and imipenem, 0% and 0.1%, respectively. These results demonstrate that LJC 10,627 has extremely high stability against renal DHP-I. PMID- 1301070 TI - Determination of (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5- tetrahydro-1H-3-benzazepin-7-ol (NNC 01-0687), a novel dopamine D-1 receptor antagonist, in plasma by solid-phase extraction and high-performance liquid chromatography. AB - A fast and reliable method has been established for the determination of the dopamine D-1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8 nitro-2,3,4,5-tetrahydro-1 H-3- benzazepin-7-ol (NNC 01-0687) in plasma. A combination of reversed-phase extraction on C18 columns and straight-phase high performance liquid chromatographic analysis with ultraviolet detection at 287 nm resulted in very clean chromatograms. The limit of quantitation was about 1 ng/ml of plasma. Validation of the method showed good selectivity, linearity, recovery, accuracy and precision. Several modifications of the method were possible with little or no influence on the assay. PMID- 1301071 TI - Reductive metabolism of diaziquone (AZQ) in the S9 fraction of MCF-7 cells. II. Enhancement of the alkylating activity of AZQ by NAD(P)H: quinone-acceptor oxidoreductase (DT-diaphorase). AB - The alkylating activity of reduced diaziquone was studied by the nitrobenzylpyridine (NBP) assay and was compared to those of the parent compound and aziridine-containing N,N',N"-triethylenethiophosphoramide (Thio-TEPA). Diaziquone (AZQ) was reduced enzymatically by 2e- using S9 cell fraction from MCF 7 cells which is rich in NAA(P)H:quinone-acceptor oxidoreductase (DT-diaphorase) (QAO) activity. One electron enzymatic reduction was performed with NADPH cytochrome c reductase. The alkylating activity of AZQ increased 3-fold when reduced by 2e-. This increase was inhibited by dicumarol, an inhibitor of QAO. In contrast, the alkylating activity of AZQ did not increase beyond that of the parent compound when reduced by 1e- using purified NADPH-cytochrome c reductase. Similar results were obtained when AZQ was reduced chemically with borohydride (2e-) and with NADPH (1e-). Anaerobic incubations of AZQ with the S9 fraction of MCF-7 cells (2e- reduction) resulted in an increase in NBP alkylation over its aerobic counterpart (1.8-fold) while maintaining the near 3-fold increase in alkylation over untreated AZQ. In contrast, AZQ incubations with NADPH-cytochrome c reductase (1e- reduction) under the same conditions did not result in an NBP alkylation increase over untreated AZQ. These results indicate that AZQ hydroquinone is most likely the responsible species for the observed alkylation of this antitumor agent to DNA and other nucleophiles. The results also suggest that NAD(P)H:quinone-acceptor oxidoreductase is a very important enzyme in the bioactivation of AZQ. PMID- 1301072 TI - GEA 857 blocks potassium channels in the membrane and, thereby, prolongs muscarinic cholinergic responses in N1E-115 neuroblastoma cells. AB - GEA 857 [2-(4-chlorophenyl)-1,1-dimethylethyl 2-amino-3-methylbutanoate], a structural analogue of the serotonin (5-HT) uptake inhibitor alaprocalate but without effects on the 5-HT uptake, was shown to potentiate muscarinic cholinergic responses in N1E-115 neuroblastoma cells. In intracellular recording experiments, GEA 857 (1 microM) increased the cell input resistance and prolonged the action potential. It also prolonged the cellular response to carbachol acting on muscarinic receptors in a manner mimicked by potassium channel blockers such as 4-aminopyridine and TEA. GEA 857 did not affect the carbachol stimulated uptake of 45Ca, but depressed the carbachol activated outflow of 86Rb from neuroblastoma cells. The conclusion drawn from these results is that GEA 857 reduces potassium conductances in the membrane in N1E-115 neuroblastoma cells and, thereby, prolongs muscarinic agonist-induced responses. PMID- 1301073 TI - Induction, purification and characterisation of acyl-ACP thioesterase from developing seeds of oil seed rape (Brassica napus). AB - The level of two thioesterases, acyl-CoA thioesterase and acyl-ACP thioesterase was determined during seed maturation in oil seed rape. Both thioesterase activities rose markedly prior to the onset of lipid accumulation, but the induction kinetics suggest that the activities reside on distinct polypeptides. Acyl-ACP thioesterase (EC 3.1.2.14) was purified 2000-fold using a combination of ion exchange, ACP-affinity chromatography, chromatofocusing and gel filtration. Using native gel electrophoresis, and assays for enzymic activity, two polypeptides were identified on SDS-PAGE as associated with the activity. Cleveland mapping of these polypeptides, of 38 kDa component and 33 kDa respectively, demonstrated that they are related. An antibody was prepared against the 38 kDa component, and this also recognises the 33 kDa polypeptide in highly purified preparations. Western blotting of a crude extract identifies one band at 38 kDa consistent with the 33 kDa component being a degradation product generated during purification. The native molecule has a M(r) of 70 kDa indicating a dimeric structure. The enzyme has a pH optimum of 9.5 and shows strong preference for oleoyl-ACP as substrate. The intact enzyme has an N terminus blocked to protein sequencing. We also found that two other polypeptides co-purify with acyl-ACP thioesterase under native conditions. The N-terminal amino-acid sequence of these polypeptides is shown and their possible identity is discussed. PMID- 1301075 TI - The relationship between spontaneous coping strategies and perceived anxiety of patients undergoing cardiac catheterization. AB - Little is known about how patients spontaneously cope with the inherent stressors of the cardiac catheterization procedure. In this study, spontaneous coping strategies were identified and the relationship between coping strategies and anxiety throughout the procedure was examined. Data consisted of 62 patients' subjective ratings of anxiety, reported at 6 points during the procedure, and the coping strategies which were used at those times. The Coping with Invasive Medical Procedures (CIMP) Scoring System was developed and utilized to examine the relationships between coping and anxiety. At various points throughout the procedure, "control" and "hoping" were associated with high anxiety, while "passive coping" and "positive reframing" were associated with low anxiety. Patients who repeatedly changed coping strategies during the procedure experienced slightly less anxiety than those using a more consistent coping approach. The results are discussed with an emphasis on patient teaching. PMID- 1301074 TI - Antiplatelet activity of the long-acting thromboxane receptor antagonist BMS 180,291 in monkeys. AB - The effects of the novel TxA2/prostaglandin endoperoxide (TP) receptor antagonist BMS 180,291 on platelet reactivity was determined ex vivo in conscious African green monkeys. Platelet aggregation responses to U-46,619 were decreased 50% and 100% at 23 to 24 hrs after BMS 180,291 oral doses of 1 and 3 mg/kg, respectively. In addition to inhibiting aggregation, a 3 mg/kg oral dose of BMS 180,291 also produced an 11 +/- 3-fold shift to the right in the U-46,619 concentration response relationship for platelet shape change at 24 hrs after dosing. When the 3 mg/kg oral dose was continued for 11 days, the shift in this concentration response relationship increased to 26 +/- 10- and 93 +/- 30-fold at 24 hrs after the 8th and 11th doses, respectively. This progressive inhibition corresponds to 93 +/- 3 and 99 +/- 1% blockade of platelet TP-receptors responsible for shape change, respectively. Comparable levels of TP-receptor blockade have been previously correlated with antithrombotic and antiischemic activities of TP receptor antagonists in vivo. Platelet reactivity to U-46,619 had completely recovered on the 7th day after the final dose of BMS 180,291, indicating effective elimination from the circulation over this interval. In separate experiments, a 3-mg/kg i.v. dose of BMS 180,291 produced only marginal and transient hemodynamic effects in anesthetized African green monkeys. Overall, these data demonstrate that BMS 180,291 given orally once a day produces a sustained and therapeutically-relevant level of TP-receptor antagonism. PMID- 1301076 TI - Discharge functional capacity and self-efficacy of men after coronary artery bypass graft surgery. AB - Fatigue and activity intolerance are reported to persist for several weeks after discharge after coronary artery bypass graft (CABG) surgery. This may be due to early discharge, which limits the time, prior to leaving hospital, to achieve an adequate functional level for the performance of many activities of daily living. Alternatively, it may be related to level of self-confidence, or self-efficacy (SE), in one's ability to perform physical activity. High SE may result in overexertion during the vulnerable, early post-discharge phase of recovery, whereas low SE may cause underexertion. The limited number of cardiac rehabilitation programs in Canada for this phase of recovery precludes close guidance and monitoring during physical activity for most patients. Prior to prescribing safe and effective home exercise at discharge, it is essential to assess functional level, cardiovascular responses to physical activity, and perceived level of confidence in ability to perform physical activity. The purpose of this descriptive study was to measure functional capacity, hemodynamic responses to low level exercise, and self-efficacy at discharge after CABG surgery. Twenty-one men completed a self-efficacy questionnaire (SEQ) and a low level graded exercise test (LL-GXT) using a modified Naughton protocol, on the day of discharge. Results revealed that discharge functional capacity ranged from 1.0 METs to 4.3 METs, peak heart rate ranged from 82-150 beats.min-1, and peak systolic blood pressure from 114-200 mmHg. Subjects were more confident in their ability to tolerate psychological stressors than physical activity. Furthermore, there was no correlation between SE for physical activity and the physiological variables except HR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301077 TI - Modifiable cardiac risk factors of obesity, inactivity, and stress: a community survey. AB - In this descriptive study the perceptions and practices of community residents concerning three risk factors associated with coronary heart disease (obesity, inactivity, and stress) and their prevalence were assessed. One thousand questionnaires were randomly mailed to residents of Thunder Bay, Ontario, Canada with a response rate of 48.1%. The results suggest that all three risk factors under study could be contributing to the significantly higher mortality rates in Thunder Bay due to coronary heart disease (when compared to provincial norms). Programs should be developed in the community under study to promote awareness of cardiac risk factors and strategies developed to reduce these risk factors. PMID- 1301078 TI - Nursing research: staff nurses' perspective. PMID- 1301079 TI - Heart valve surgery: nursing issues. PMID- 1301080 TI - The perceptions of stressors in coronary artery bypass graft patients. AB - A descriptive correlational study was conducted to compare the perceptions of 33 patients and their nurses of the stressors involved in the surgical procedure of Coronary Artery Bypass Graft (CABG). Five additional stressor items were added to the Stressor Scale developed by Carr (1982). Patients and nurses completed the questionnaires. Correlations and t tests were used to examine the relationship between the stressor scores. Overall, the nurses rated the stressors significantly higher than the patients. In the nursing group, nurses with more experience rated the stressors significantly lower than the nurses with less experience. These results were similar to the findings of Carr (1982). Implications for nursing theory, practice and research are discussed. PMID- 1301081 TI - Xenopus Gastrulation without a blastocoel roof. AB - The objective of this paper is to determine the function in gastrulation of several of the five major regional morphogenetic processes in the African clawed frog, Xenopus laevis. These regional processes are (1) epiboly of the animal cap (AC); (2) migration of the mesoderm on the roof of the blastocoel; (3) convergence and extension of the dorsal, noninvoluting marginal zone (NIMZ); (4) formation of the bottle cells at the site of blastopore formation; and (5) convergence and extension of the involuting marginal zone (IMZ). After the AC and the NIMZ were removed, thus eliminating the first three of these processes, the IMZ involuted, constricted, and closed the blastopore. It also converged and extended to form notochord and somites, although these tissues were often crooked and sank into or were covered over by the vegetal endoderm. When the AC was removed, the dorsal axial mesoderm involuted and stuck to the inner surface of the NIMZ. The IMZ and NIMZ converged and extended together to form a longer, straighter axis than that formed by the IMZ alone. Moreover, presence of the NIMZ also prevented the sinking of the IMZ into the endoderm. Misalignment of the available AC-NIMZ substratum and the IMZ at the beginning of gastrulation suggested that the IMZ determines the general direction of its own extension. Absence of the AC-NIMZ accelerated and increased the normal effects of bottle cell formation on the IMZ and vegetal endoderm. In absence of the AC-NIMZ as a substratum on which to migrate, prechordal mesoderm was pushed anteriorly by the converging and extending mesoderm behind it, but it did not spread normally. We conclude that (1) involution and blastopore closure by the IMZ can occur without pushing by epiboly and convergence and extension of the NIMZ-AC; (2) involution and blastopore closure can occur without migration of the mesoderm on the blastocoel roof; (3) convergence and extension of the IMZ are sufficient to bring about IMZ involution and blastopore closure; (4) the function of bottle cells in initiating involution is retarded by presence of the NIMZ-AC; (5) the associated dorsal NIMZ and IMZ together form an axis that extends better and is perhaps stiffer than the IMZ alone; and (6) the dorsal axial and paraxial mesoderm form the "skeleton" around which the mechanics of the other parts of the embryo are organized. These findings are important for the analysis of gastrulation by cellular, genetic, and molecular approaches. PMID- 1301082 TI - Cellular contribution of the different regions of the somatopleure to the developing limb. AB - Regionalization of the presumptive limb region was examined before and at the onset of limb development by means of a variety of transplantation experiments between quail and chick embryos in ovo. The results demonstrate a two-step process, the first of which is the designation of the region of the somatopleure that would become part of the limb, followed by specification of dorsal and ventral regions of the limb. The medial half of the somatic mesoderm is the region which gives rise to the limb with only a smaller cellular contribution from the lateral half of the somatic mesoderm. The cellular contribution of the medial region of the somatopleure appeared to determine the type of limb formed (i.e., wing or leg). The second process relates to changes in the ability of the somatic ectoderm to undergo extensive lateral displacement with development. Starting at stage 14, the medial and lateral somatic ectoderms maintain their position after transplantation, in contrast to earlier stage limb or flank ectoderms which undergo extensive lateral displacement with development. The positional determination of the dorsal and ventral properties of the medial and lateral ectoderms of the prospective limb region and their distal displacement during limb outgrowth may be important morphogenetic events in limb development. PMID- 1301083 TI - Cell interactions influence the pattern of biomineralization in the Ilyanassa obsoleta (Mollusca) embryo. AB - Ilyanassa obsoleta larvae have two calcium carbonate-containing organs, shell and statocyst, which are derived from five micromere cells (2a, 2c, 2d, 3c, 3d). "Internal shell," an abnormal, internal calcium carbonate mass, was previously observed when cells which normally induce shell and statocyst were removed. This study utilizes multiple-cell deletions to examine how these calcium carbonate producing precursors control the pattern of biomineralization, whether it is in external shell, statocyst, or internal shell. It was demonstrated that internal shell was solely derived from any of these five cells. However, there was a quantitative difference in the frequency of internal shell production depending upon which cells, as well as how many, are deleted. In general, when external shell or statocyst production was diminished, as the result of removing several of the calcium carbonate-producing cells, internal shell was deposited instead. The presence of internal shell can best be explained as the result of altered interactions between these five cells after one or more have been deleted. Electron diffraction and transmission electron microscopy show that internal shell differs from normal shell in both structure and crystal morphology and it can also be produced by statocyst precursors. Thus, both the deletion and electron microscopy data support the interpretation that the development of internal shell is controlled by shell- and statocyst-producing cells when the cell communication between these cells is disrupted. PMID- 1301084 TI - Stripe selection: an intrinsic property of some pattern-forming models with nonlinear dynamics. AB - In two-dimensional pattern formation, the genesis of stripped rather than spotted patterns may involve preexisting spatial asymmetries, such as unidirectional gradients or asymmetric shape of the pattern-forming domain. In the absence of such asymmetries, some kinds of nonlinear dynamics still lead to striped rather than spotted patterns. We have studied the latter effect both by extensive computer experiments on a range of nonlinear models and by mathematical analysis. We conclude that, when the dynamic equations are written in terms of departure from the unpatterned state, the presence of nonlinearities which are odd functions of these departures (e.g., cubic terms) together with absence of even nonlinearities (e.g., quadratic terms) ensures stripe formation. In computer experiments, we have studied the dynamics of two-morphogen reaction-diffusion models. The mathematical analysis presented in the Appendix shows that the same property exists in more generalized models for pattern formation in the primary visual cortex. PMID- 1301085 TI - Neurofibromin, a predominantly neuronal GTPase activating protein in the adult, is ubiquitously expressed during development. AB - The onset of manifestations of the common, autosomal dominantly inherited disease type 1 neurofibromatosis (NF1) is usually in childhood. To begin to understand the pathogenesis of NF1, we analyzed the developmental pattern of expression of the protein product of the NF1 gene, neurofibromin, by Western blotting and immunohistochemistry using the rat as a model system. Neurofibromin is uniformly distributed throughout embryonic day 10 and 12 rat embryos. By embryonic day 16, neurofibromin immunoreactivity is enriched in neurons of the cortical plate, in peripheral ganglia, and in developing CNS and PNS fiber tracts, but remains detectable outside the nervous system. Expression decreases in nonneural tissues by postnatal day 6, and neurofibromin is greatly decreased (lung, adrenal cortex, skin) or absent (skeletal muscle, cartilage) in adult tissues except for brain, spinal cord, peripheral nerve, and adrenal medulla. Transient expression of neurofibromin during development in many tissues suggests the importance of this GTPase-activating protein in morphogenesis and organ growth. A separate role is proposed for neurofibromin in growing axons and in the mature nervous system. PMID- 1301086 TI - [The nature of synergism in water disinfection processes with mixtures of chemical disinfectants]. PMID- 1301087 TI - [Functional differences of lactate dehydrogenase from muscles of fish adapted to various environmental temperatures]. PMID- 1301088 TI - [Free arachidonic acid as a messenger and modulator in the mechanism of the hydroosmotic effect of vasopressin]. PMID- 1301089 TI - [Etiological mechanisms of population homeostasis in Mongolian gerbils (Meriones unguiculatus)]. PMID- 1301090 TI - [DTNB-light chain affects the conformation of the myosin head complexed with ADP and vanadate]. PMID- 1301091 TI - [Interaction of oligonucleotides with a recombinant CD4 receptor]. PMID- 1301092 TI - [Development of an integrated software program to analyze statistically the results of complex investigations in space biology and medicine]. AB - A concept of implementing the problem-oriented statistical software based on an application of expert systems is presented. The shortcomings of existing statistical software for personal computers and trends of their improvements are analyzed. Recommendations on designing of statistical expert systems can be used by the statisticians, mathematicians, programmers and users not being professionals in these fields. Integrated statistical software will make it possible to perform additional retrospective analysis and to check up the large arrays of previously gained data and to obtain supplementary scientific information and to find new regularities in the previous experimental findings. PMID- 1301093 TI - [Pattern of spontaneous oculomotor activity in weightlessness and the readaptation period]. AB - The results of one part Spontaneous Oculomotor Activity Study of Soviet-Bulgarian experiment "Labyrinth" conducted with the participation of 5 cosmonauts prior to and after 10- and 241-day flight are presented. Two cosmonauts have also been studied in-flight. The experiment was conducted with the use of automated data controlling and processing system "Zora" developed by the Bulgarian specialists on a personal computer basis. The horizontal and vertical electrooculograms were recorded in the subjects with eyes closed, open and open but shaded by opaque glasses with the gaze directed forward and in extreme left, right, up and down directions of the gaze. It is found that in the first 3 day of space flight especially when locking visual input, there is an increase in spontaneous activity of "swimming" and saccadic nature or spontaneous nystagmus mainly in the vertical direction. There have been sharp decreases in the rate of eye movement and increase of an amplitude when placing the eyes in the extreme positions (especially in up-down directions) accompanied by correcting saccades or adaptive nystagmus. The post- and inflight changes in the severity and pattern of spontaneous oculomotor responses were similar. PMID- 1301094 TI - [Adaptation of young pilots to new conditions of professional activities (socio psychological aspects)]. AB - An adaptation of 146 young pilots to the flying career conditions was studied. The pilots filled in the questionnaire containing the points on: motivation, flight duty satisfaction, self-assessment of professional advancements and conditions under which it occurs and an attitude to flying personnel of the unit. The experimental findings can be used to improve the psychological relations of the young pilots during their adaptation to the new conditions of professional activity. PMID- 1301095 TI - [Hemodynamic status of man in a graded orthostatic test]. AB - Fourteen volunteers were exposed to a graded orthostatic test by a passive tilt from the horizontal position (0 degree) to an orthostatic posture (70 degrees) with intermediate angles of 10, 20, 30, 40, 50 and 60 degrees. Each position was maintained for 5 min. At the end of each step ECG, the first derivative of impedance cardiogram and auscultative blood pressure were registered. Stroke volume, cardiac output, Q-Z interval, thoracic impedance and diastole-systolic coefficient of impedance cardiogram (the parameter of pre-loading) were most markedly changed at the beginning of the test, when the tilt angle was less than 30 degrees. Its further increase was associated with moderate changes of the mentioned parameters. Diastolic arterial pressure began growing significantly from the tilt angle of 10 degrees and the cardiac rhythm became significantly more frequent starting from 30 degrees. Thus, the set of parameters registered becomes more informative if the test is performed in a graded manner since in this case it is possible to evaluate the order and magnitude of passive and active hemodynamic changes, and on the basis of their comparison to assess the adequacy of compensatory circulatory responses to orthostatic exposure. PMID- 1301096 TI - [Maximal anaerobic capacity of man in a modified Wingate test]. AB - We studied the possibility of using a 380B Siemens-Elema (Sweden) bicycle ergometer to determine the maximal anaerobic capacity of healthy subjects during a modified Wingate test. Exercise was performed under stable moment conditions, with calculation of braking resistance on the basis of the subjects lean body mass. The values of total work performed and maximal power may be used for comparative evaluation of physical work capacity in participants of training and rehabilitation programs. PMID- 1301098 TI - [Role of ultraviolet radiation and vitamin D metabolism in medical care during space flights]. AB - Data on the development of ultraviolet (UV) deficiency in the cosmonauts are analyzed, possible ways to optimize UV radiation and alimentary stearin supply in order to prevent vitamin D deficiency and to correct the changes in phosphorous calcium metabolism are discussed. PMID- 1301097 TI - [Informative value of rerespiration as a method for evaluating functional reserves of the cardiorespiratory system in modeling of some flight factors]. AB - This article presents a study of the informative value of the recurrent breathing (rerespiration) method developed by the authors, for evaluating the functional status of the human body during recovery after exposure to noise and vibration, to piloting accelerations and head-down hypokinesis. It is shown that a 1.5-h exposure to noise and vibration increases tolerance to rerespiration, suggesting a stimulatory effect. A 5-h exposure in half of cases either does not change tolerance to the test or lowers it. Piloting head-to-seat accelerations of 7 to 9 G are associated with a lowering in tolerance to rerespiration, the functional status being recovered 1 d later. A similar exposure to 3-5 G in 83% of cases is not associated with an alteration of response to the test. After a 30-day head down hypokinesis there is a lowering of tolerance to rerespiration, both in subjects with drug correction and in the control group. On day 10 of recovery in the control group return to the baseline rerespiration tolerance level was incomplete. Medically treated subjects demonstrated a complete recovery. Thus, rerespiration in the developed methodological version, is an informative loading test allowing to evaluate the dynamics of the functional status of the body. As a signal method it helps to clarify the individual duration of recovery after performing flight-related tasks, to substantiate the necessity of rehabilitation procedures and assess their effectiveness, as well as to detect persons with a stable decline of tolerance to rerespiration. PMID- 1301099 TI - [Oxygenation of the frontal cerebral cortex in monkeys during a two-week space flight]. AB - In monkeys (Macaca mulatta) during a two-week space flight and in a ground-based control experiment, with semi-closed platinum electrodes, partial oxygen pressure (pO2) was registered in the frontal cerebral cortex. It was shown that during the flight there is a marked increase of pO2 in the frontal cortex, reaching maximal values on days 5-8 (up to 203%) with a subsequent tendency to normalization by day 11. In the control experiment pO2 values in the cortical zone studied did not exceed the baseline level throughout the period of registration. Analysis of the curves of pO2 oscillations in the frequency range from 0.2 to 0.01 Hz in-flight revealed a shift of the oscillation power spectrum in the long-wave direction which was not seen in the control experiment and suggested a decreased rate of tissue metabolism. As a possible explanation for the noted effects of pO2 dynamics during weightlessness, a combination of a decreased metabolic rate in the brain segment under study with a disorder in the mechanism of regulation of local cerebral blood flow is suggested. PMID- 1301100 TI - [Effects of hypokinesia on cardiac activity in rats with high and low spontaneous motor activity]. AB - Hypokinesia effects on cardiac contractivity and vegetative regulation were studied in rats with high and low spontaneous motor activity. It was shown that hypokinesia promotes depression of the stroke volume and decrease of sympathetic nervous activity in rats with low motor activity. At the same time, in rats with high motor activity these parameters were not significantly affected by hypokinesia. The conclusion is made about a relationship between resistance to hypokinesia and spontaneous motor activity. PMID- 1301101 TI - [Accumulation of calcium ions in myocardial sarcoplasmic reticulum of restrained rats exposed to the pulsed electromagnetic field]. AB - Alteration in the velocity of Ca++ accumulation was investigated in myocardial homogenates from restrained rats which were chronically (1 and 2 months) exposed to the impulse electromagnetic field with frequency 1 Hz and magnetic induction 6 24 mT. The fall of the studied variable by 33% was observed in a month while restoration of the velocity of Ca++ transport was shown after two months of exposure. The results are discussed in terms of the organism adaptation to physico-chemical and physiological impacts. PMID- 1301103 TI - [Age factors and flight duration in chronic diseases]. AB - Health disqualification is the main reason for stopping flying activity. The age limitations of flying activity have been not established. Nevertheless, the development of diseases and motivated continuation of flying activity are severely age-dependent. The cases of chronic diseases have been reported throughout the all flying careers of 1,433 pilots and navigators and disqualifying for flying activity for the health condition upon routine medical screening. The flying activity duration after a disease occurrence was found to be of bimodal distribution. The first peak coincides with the moment of an initially diagnosed illness, the second-delayed peak in elder individuals approximates the first one. Thus, in the persons in whom a chronic disease was initially diagnosed when they were twenty years old, this diagnosis was confirmed in 18-20 years and in 2-4 years in the persons in whom a disease was diagnos ++ when they were 35 years old. Thus, there are two factors greatly affecting the disqualification--a disease and age. Both these factors are closely interrelated. PMID- 1301102 TI - [Significance of comparing the results of caloric and vestibulometric rotation tests]. AB - The use of modified, less laborious, easier endured vestibulometric tests made it possible to facilitate diagnosing Meniere's disease and neurinomas of the vestibular nerve. Comparison of nystagmometric findings recorded in the same patient during caloric and rotation tests using the diagnostic model of a bithermal test permitted some assumptions to be made in relation to the mechanisms for nystagmogenesis associated with pathologic states in ear labyrinth and vestibular portion craniocerebral (VIII) nerve. It is found that in the majority of Meniere's disease cases (61%) there is a decrease in an intensity of caloric nystagmus induced by Lasix dehydration effect. This phenomenon can be explained by a reduced difference in energy levels of two complexes of vestibular nuclei and, therefore, by an attenuated afferents to peripheral compartment of vestibular system. In neurinoma of aural nerve, the phenomenon of vestibular recruitment (20%) was noted. The diagnostic model of a bithermal test makes it possible to explain an effect of smoothing out the nystagmic responses induced by an intensive stimulus when used a sinusoidal stepwise test. The observed vestibular recruitment results from the severe disorder of one of the afferent inputs due to destruction of induced by tumor pressure. PMID- 1301105 TI - [New technology for the analysis of ultraviolet measurements for the purpose of physical examination in aviation]. PMID- 1301104 TI - [Rationale for using helium-neon laser in medical rehabilitation of patients with atrophy]. AB - High resolution measurements of helium-neon laser spectra have been conducted about 0.64 mm wavelength. The singlet oxygen photo-generation was demonstrated to be responsible for the bioeffects of this spectral interval. Helium-neon radiation with 0.633 mm wavelength was used for medical rehabilitation of 15 patients with muscular atrophy as a result of wearing immobilizing plaster arm bends on lower extremity fractures. 50-day hypokinesia of a damaged extremity induced differences in functional indices between damaged and healthy extremities in the same patient. This difference was diminishing more rapidly after laser therapy than in the control group though all patients had adequate rehabilitative treatment. Due to the likelihood of hypokinesia- and weightlessness-induced atrophies, helium-neon laser may be recommended for atrophy prophylaxis and treatment in both cases. PMID- 1301106 TI - [Mathematical modeling of a system to change and maintain the pressure of breathing gas mixture in the altitude chamber]. PMID- 1301107 TI - [Optimization of selecting the number of measurements with a systematic error of measuring tracts]. PMID- 1301108 TI - [Effect of the weak magnetic field of the Earth on cellular composition of spermatogenic epithelium of testes in rats]. PMID- 1301109 TI - [Radiation environment on the board of passenger air-liners ]. PMID- 1301110 TI - [Some specifics of providing the vitamin C, B1, B2 and B6 supplements to canned food during extended space missions of man]. PMID- 1301112 TI - Health-related quality of life research. PMID- 1301111 TI - The CARES: a generic measure of health-related quality of life for patients with cancer. AB - In spite of the prevalence of neoplastic disorders as a cause of chronic illness, very few of the currently available generic measures of health-related quality of life or health status have been utilized with cancer patients. In this paper we reviewed our studies with the Cancer Rehabilitation Evaluation System (CARES), a cancer-specific measure of rehabilitation needs and quality of life. We present data to demonstrate that the CARES is a generic measure of health-related quality of life, suitable for use in the many different diseases called cancer. The data that form the basis for this paper were collected during a decade of research on the CARES. This paper represents the first discussion of the performance of the CARES across separate cancer sites and phases of the disease. In addition, we demonstrated that the CARES is responsive to changes in health-related quality of life over time. Finally, we will discuss the application of the CARES in clinical and research settings. PMID- 1301114 TI - Assessing quality of life in head and neck cancer. AB - Comprehensive assessment of the impact of head and neck cancer goes beyond traditional biomedical outcomes to include quality of life. This paper examines the methods used in reported studies on quality of life in head and neck cancer patients with respect to definitions, approaches to measurement, and types of findings. Analysis reveals little consensus in defining or assessing quality of life, although deficits in patient well-being were well-documented. A number of current efforts to develop and validate quality of life instruments specific to cancers of the head and neck have been reported. Future research should be sensitive to the issue of defining quality of life; a definition which includes both patient perceptions and objective functioning in a number of areas is advisable. Investigators should build on recent and ongoing efforts at instrument development and make efforts to incorporate quality of life assessment in clinical trials of cancer treatments. The distinctive aspects of head and neck cancer illustrate the importance of considering characteristics of the patient population in quality of life research and also the way that quality of life data can contribute to the multidisciplinary team of caregivers. PMID- 1301113 TI - Is there a role for preference assessments in research on quality of life in oncology? AB - The development of ways to evaluate interventions that may have an impact on quality of life is a rapidly-developing area of research in clinical oncology, especially within the context of randomized controlled trials. We propose a role for assessments of preferences in such evaluations, including preference studies designed to assess attitudes toward the clinical acceptability of interventions, and preference trials designed to assess choice behaviour in relation to interventions. We suggest that such preference assessments represent a specific case of a more general issue: the need to develop an 'ethics of evidence', that is, standards for the creation, assessment and communication of evidence. We then outline a framework within which an 'ethics of evidence' might be developed, and suggest that the framework also may provide a useful model for the processes involved in the transfer of research results into clinical practice. As an illustration, we consider the problem of decision making in circumstances where the choice of therapy depends primarily on the patient's own preferences, as, for example, in the choice of mastectomy or breast-conserving treatment in early stage breast cancer. The long-term goal is to develop criteria which might be used to foster shared rational decision making in such circumstances. PMID- 1301115 TI - Patient acceptance and differential perceptions of quality of life measures in a French oncology setting. AB - A three-part study evaluated French cancer patients' acceptance of self-rated quality of life measures, the predictive value of these measures, and the agreement between patient and health provider ratings of patient quality of life. In part one, 93% of 137 patients indicated a willingness to complete the Qualite de la Vie-Questionnaire (QOL-Q) and Analogues Lineaires pour la Mesure de la Qualite de vie (LA), and 63.6% indicated a willingness to be interviewed by a psychologist. Willingness to complete the scales was related to hospitalization status and treatment modality. In parts two and three, 100 patients were asked to complete the QOL-Q, LA, the Karnofsky Index (KI) and a side-effects checklist, and to undergo a psychological interview. Following interview, a psychologist rated the patients using the QOL-Q, and classified patient level of emotional distress. Oncologists rated the patient using the KI and the side-effects checklist. The results indicate that the patients' ratings of their quality of life were higher than the psychologist's ratings, and that the QOL-Q has predictive value in identifying severe emotional distress. Low level of patient and physician agreement on the KI was partially explained by patient age and cancer site. A moderate level of agreement was found between patient and physician perceptions of side effects. The study suggests that the QOL-Q, not the LA, may be useful as a screening tool to identify patients with impaired quality of life, and that self-rated measures should be included in quality of life assessments. PMID- 1301116 TI - Reliability and validity of the Katz Adjustment Scales in an epilepsy sample. AB - Development of quality of life measures de novo is time-consuming and expensive, and a number of instruments are already available for general use. Reevaluation and refinement of quality of life tools are needed to improve the existing pool of measures. In this study, data from a sample of 328 epilepsy patients were used to revise a measure of social adjustment and emotional status developed in the 1960s, the 127-item form R1 of the Katz Adjustment Scales (KAS-R1). Using a comprehensive item analysis procedure, we increased the number of items used in scoring the KAS-R1 from 76 to 113 and substantially improved the reliability of scales in both the original sample of 328 epilepsy patients and in a second administration to a 'cross-validation' sample of 193 epilepsy patients. Support for the validity of the revised KAS-R1 scoring system was obtained in a known groups analysis of patients who had previously undergone surgery for epilepsy: mean scores were significantly higher (p < 0.05) on 11 out of 14 scales in the revised KAS-R1 for patients who were completely seizure-free compared to patients who were having seizures with loss of consciousness, after adjusting for age, gender, and anticonvulsant medication use. PMID- 1301117 TI - Responsiveness to change: an aspect of validity, not a separate dimension. AB - Assessment of health-related quality of life is accelerating in naturalistic observational studies, clinical trials, and clinical practice. Some researchers have argued that the ability of a quality of life instrument to detect clinically important changes over time, "responsiveness," is a distinct psychometric property from the measure's reliability and validity. We discuss the important implications of this argument and counter that responsiveness is actually one indication of a measure's validity. PMID- 1301118 TI - A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity. AB - International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles. PMID- 1301119 TI - Psychosocial, neuropsychological and neurological status in a sample of heart transplant recipients. AB - The sample for this psychosocial follow-up study was formed using the 71 surviving patients from a total of 100 who underwent heart transplantation up until March 1990 at Kiel University Hospital. Forty of these could be investigated comprehensively. The neurological investigation comprised EEG and auditory and visually evoked potentials. The psychological investigation started with several neuropsychological tests; additionally all patients were interviewed and they completed questionnaires concerning anxiety, depression, ways of coping, personality characteristics and life satisfaction. Within the entire sample, there were few indications for specific psychological impairment. The psychosocial status of the patients was not significantly related to the time which had elapsed since they underwent transplantation. There were few associations between neuropsychological and psychosocial data, and several indicators of early postoperative complications which are described in the literature (e.g., length of stay in the intensive care unit). Clinically relevant subgroups (formed on the basis of neuropsychological test results, anxiety and depression) did not differ in terms of these indicators. Nevertheless, a considerable proportion of the patients (25%) were characterized by having a higher level of affective and neuropsychological impairment. Although based upon retrospective investigations, the results of this follow-up generally correlate with those gained from Anglo-American countries. In interpreting the results one needs to consider the possible influence of premorbid personality characteristics as well as denial which may be typical for patients undergoing heart transplantation. PMID- 1301120 TI - Assessment of validity and clinical application of an Italian version of the Rotterdam Symptom Checklist. AB - An Italian version of the Rotterdam Symptom Checklist (RSCL) has been validated in a sample of 147 healthy women and 61 breast cancer outpatients. The structure of the RSCL has been analysed by factor analysis reproducing results of the English version, and the psychological and physical subscales showed a good internal reliability (Chronbach's alpha 0.91; 0.87). The State-Trait Anxiety Inventory questionnaire and the RSCL were compared in the healthy women sample. A Pearson correlation coefficient (PCC) of 0.74 (p < 0.01) was found between the trait anxiety and RSCL psychological scores. Psychological (mean: 17.5; SD: +/- 5.4) and physical (mean: 37.8; SD: +/- 8.6) subscale scores were correlated in healthy women (PCC: 0.68; p < 0.01) and related to a general wellbeing item (PCC: 0.44; p < 0.01). The breast cancer outpatients showed scores for psychological and physical subscales similar to those in the healthy women sample. The Italian version of the RSCL seems comparable to the English version and could be useful in clinical research. Its use in longitudinal studies should be tested. PMID- 1301122 TI - Issues of concern in the standardization and harmonization of drug trials in Europe: health-related quality of life, ESCT meeting, Strasbourg, 23-24 May 1991. AB - Overviews of the development of the concept of quality of life from a medical viewpoint, and the need for new models and methods to assess health-related quality of life were presented, along with WHO, FDA and European regulatory viewpoints and a discussion on the measurement and valuation of health by social judgement, at the health-related quality of life session at an ESCT meeting on issues of concern in the standardization and harmonization of drug trials in Europe. It was concluded that, for the present, all three types of measurements of quality of life--individual, disease-specific, and generic scales--should be used in research to look for convergent versus divergent validity. PMID- 1301121 TI - Severity of disease and quality of life: a comparison in patients with cancer and benign disease. AB - The aim of our study was to compare the quality of life in patients with malignant and benign diseases. Eighty-nine females and 110 males (mean age 59 years) from the surgical unit at the University Hospital of Linkoping were examined. Ninety-five subjects suffering from a gastrointestinal malignancy were compared with 104 non-malignant patients, of which 57 had benign gastrointestinal disorders, 24 endocrine and 23 vascular diseases. Quality of life was defined as perceived well-being and life satisfaction, globally as well as within key domains. Two separate types of self-ratings, a life domain (20 items) and a well being rating (eleven subscales, each scale with ten items), were performed in the medical ward. The life domain rating covered the subject's own appraisal of his health and psychological circumstances; social network; activities and habits; of a structural domain ('ability to lead a meaningful life') and of his global life satisfaction. The well-being rating focused on emotional experiences (basic mood, security, indolence, loneliness, inferiority, and guilt together with future orientation) and perceived behaviour (endurance, tension, sociability and attitudes of the environment). The patients who had a gastrointestinal malignancy scored consistently 'lower' than patients with benign diseases. After adjusting for age concerns, most of the significant inter-group differences remained. After adjusting for nutritional state influences (e.g., recent weight loss), differences in global life satisfaction, future-orientation and perceived attitude from the environment were still apparent. This study is contrary to several other studies undertaken in search of expected group differences but none were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301123 TI - An overview of generic health-related quality of life measures for HIV research. AB - This paper provides a selective review of instruments currently being employed to evaluate generic health-related quality of life in studies of persons with human immunodeficiency virus (HIV). Instruments examined include the Quality of Well Being Scale, the HIV Overview of Problems/Evaluation System, the COOP Charts, and six Medical Outcomes Study-based measures: the SF-20, SF-30, AIDS-HAQ, SF-36, SF 38 and SF-56. Relative strengths and weaknesses of the measures are discussed. PMID- 1301124 TI - The short-term effect of patient health status assessment in a health maintenance organization. AB - This study was designed to test the short-term effects of health assessment on the process of care and patient satisfaction. The 29 Chart physicians used the Dartmouth COOP Charts to measure their adult patients' health status during a single clinical encounter; the 27 control clinicians used no measure of health status. We compared the change between baseline and post-intervention information for a sample of all study clinicians' patients. Most of the patients were female (67%), well educated (70% had at least a college education) and young (approximately 90% were aged 59 years or younger). We found that the ordering of tests and procedures for women was increased by exposure to the COOP Charts (52% vs. 35%; p < 0.01); the effect in men was not as significant (37% vs. 23%: p = 0.06). Although women reported no change in satisfaction with care, men claimed that the clinician helped in the management of pain (p = 0.02). We conclude that the use of health status measures during a single clinical encounter in an HMO changes clinician test ordering behaviour and may improve the help male patients receive for pain conditions. The long-term impact of these management changes is not known. PMID- 1301125 TI - Uncertainty, appraisal and quality of life. AB - This study evaluates the influence of different factors in the adaptation process activated by uncertainty in illness on health-related quality of life. The sample included 100 women (mean age = 52.1 years) receiving treatment for newly diagnosed (M = 5.1 months) gynaecological cancer (38 cervical, 26 ovarian, 24 endometrial, 7 uterine, 4 vulvar, and 1 vaginal). Stepwise regression analyses identified mood states, ambiguity about illness-wellness state, danger-focused appraisal and mastery as key predictors of four health-related quality of life scores. The variance accounted for by those variables is reflected in cumulative multiple R2 of 0.56 for total quality of life score, 0.57 for psychosocial well being, 0.235 for physical well-being and 0.25 for disease/symptom distress. These variances do not reflect the contribution of age, time since diagnosis, metastasis and stage of cancer which were forced to enter the regression equation first. The latter set of variables accounted for a smaller portion of the variance in health-related quality of life (R2 = 0.03-0.195). Coping strategy did not predict health-related quality of life. These findings provide beginning support for conceptualizing health-related quality of life as the outcome of an adaptation process explained by the uncertainty in illness theory. However, uncertainty in illness theory may not be sufficient to predict quality of life outcomes. Future research should consider the addition of discrepancy theory to guide the selection or development of a health-related quality of life measure, to account for the perceived discrepancy between actual experience and expected well-being. PMID- 1301126 TI - Quality of life during rehabilitation after coronary artery bypass surgery. AB - The effect of a three-phase comprehensive rehabilitation programme on the quality of life during the first postoperative year after coronary artery bypass surgery was studied in 205 male patients randomly allocated into a rehabilitation (R) and a hospital-based treatment (H) group. The rehabilitation programme included physical exercise, relaxation training, psychological group sessions, dietary advice and discussions about postoperative treatment of coronary disease. There was no difference between R and H groups in the frequency of postoperative complaints, number of hospital admissions and satisfaction of sexual life. An almost significantly greater number of subjects in R group than in H group perceived their health as good 12 months after surgery. The Beck Depression Index score decreased significantly in R group but not in H group during follow-up. A greater increase in hobby activities was observed in R group than in H group. More subjects in R group than in H group considered rehabilitation important for recovery, whereas more patients in H group considered support by the spouse and family, the subjective mental strength and a secure income as important. PMID- 1301127 TI - Clinical outcome and emotional-behavioural status after isolated coronary surgery. AB - In order to evaluate clinical and psychosocial results of isolated coronary artery by-pass graft (CABG) we studied 626 consecutive patients, mean age 61 +/- 8 years (86% men), in a follow-up (median: 58 months) with a complete questionnaire about cardiosurgical problems (post-operative vital status, angina relapse, infarction, heart failure, PTCA, redo, PM) and psychosocial variables (mood, irritableness, job satisfaction, hobby satisfaction, family relations, sexual activity, general well-being and work status). Global evaluation improvement of psychosocial variables was found in 71% of patients without cardiac events (group A) and 11% of patients with cardiac events (group B); worsening was found in 2% of group A and 1% of group B; no referred variations in 13% and 2% respectively (p < or = 0.05. Interests (in work, hobbies and sexual activities) demonstrate an improvement in 20% (group A) and 2% (group B); worsening in 12% (group A) and 4% (group B); no variations in 51% (group A) and 11% (group B) (p < or = 0.005). Patients reported a well-being evaluation improvement about 66% in the group returning to work without restriction, 13% in those with limitation, 6% no further working; worse or unchanged well-being evaluation was found in 9% of patients returning to work without restriction, 3% with limitation, 3% no further working (p < or = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301129 TI - The Quality of Life Committee of the Clinical Trials Group of the National Cancer Institute of Canada: organization and functions. AB - The Quality of Life Committee of the National Cancer Institute of Canada Clinical Trials Group has successfully advocated the adoption of quality of life outcomes in Canadian clinical trials in patients with cancer. It has developed a policy promoting quality of life assessment in phase III trials and developed writing guidelines to assist clinical investigators when developing protocols for proposed studies. As a result, all phase III clinical trials instituted since the policy was developed have quality of life assessment as a part of their objectives. It has assisted the Clinical Trials Group office personnel in the development of procedures for the conduct of quality of life assessments in clinical trials with the result that the completion rate of self-report questionnaires is very high. The Committee maintains contact with other clinical trials groups and organizations having an interest in measuring quality of life in cancer. PMID- 1301128 TI - Methods for assessing quality of life in the cardiac arrhythmia suppression trial (CAST). AB - The CAST was a randomized, double-blind placebo-controlled multicentre trial of antiarrhythmic medications designed to suppress ventricular arrhythmias in patients after an acute myocardial infarction (MI). A collection of 21 items derived from established scales was used to assess aspects of quality of life in CAST. The questions focused on symptoms, mental health, physical functioning, social functioning, life satisfaction, and life expectancy. Additional aspects included exposure to major stressful life events, and perceived social support and social integration. Work status was also recorded. Using the baseline values of 1465 (98%) out of 1498 patients enrolled in the CAST main study between 15 June 1987 and 19 April 1989, the reliability and validity of the scales used in CAST were computed. High internal consistency reliability (> or = 0.70) was found for Symptoms, Mental Health, and Physical Functioning. The discriminative validity, in particular for Symptoms, Mental Health, Physical and Social Functioning, showed that patients with heart failure and previous MI, as well as those suffering from angina and dyspnea, had a worse quality of life than those patients who were not experiencing these symptoms. It was concluded that the scales selected to form the CAST quality of life questionnaire were both reliable and clinically valid for this patient population and therefore could be used to detect disease progression and treatment effects. PMID- 1301130 TI - Statistical analysis of longitudinal quality of life data with missing measurements. AB - The statistical analysis of longitudinal quality of life data in the presence of missing data is discussed. In cancer trials missing data are generated due to the fact that patients die, drop out, or are censored. These missing data are problematic in the monitoring of the quality of life during the trial. However, by means of assuming that the cause of the missing data lies in the observed history of the patients and not in their unobserved future, the missing data are ignorable. Consequently, all available data can be used to estimate quality of life change patterns with time. The computations that are required are illustrated with real quality of life data and three commonly used computer packages for statistical analysis. PMID- 1301131 TI - Reconstruction of the 2.4 Mb human DMD-gene by homologous YAC recombination. AB - The human dystrophin gene, mutations of which cause Duchenne and Becker muscular dystrophy, measures 2.4 Mb. This size seriously limits its cloning as a single DNA fragment and subsequent in-vitro expression studies. We have used stepwise in vivo recombination between overlapping yeast artificial chromosomes (YACs) to reconstruct the dystrophin gene. The recombinant YACs are mitotically stable upon propagation in haploid yeast cells. In contrast, specific combinations of YACs display a remarkable mitotic and meiotic instability in diploid cells. Non disjunction is rare for overlapping YACs, but increases upon sporulation of diploid cells containing non-overlapping molecules. We have exploited this feature in a three-point recombination to bridge a 280 kb gap between two non overlapping YACs for which no YAC of proper polarity existed. Our largest recombinant YAC measures 2.3 Mb and contains the entire muscle specific DMD-gene with the exception of a 100 kb region containing the in-frame exon 60. The latter segment has a high tendency to undergo deletions in multi-molecular interactions, probably due to the presence of as yet unidentified instability-enhancing sequences. Fluorescent in situ hybridizations confirmed that the 2.3 Mb DMD YAC contained Xp21-sequences only and indicated a compact tertiary structure of the DMD-gene in interphase lymphocyte nuclei. We conclude that the yeast system is a flexible, efficient and generally applicable tool to reconstruct or build genomic regions from overlapping YAC constituents. Its application to the human dystrophin gene has provided many possibilities for future studies. PMID- 1301133 TI - Beginning or end? Telomere structure, genetics and biology. AB - The word telomere derives from the Greek word telos meaning 'end', roughly translating as 'the thing at the end' when the end is that of a chromosome. Telomeres belie their apparent simplicity of structure by being involved in a wide range of diverse biological phenomena. Much of our understanding of telomere behaviour comes from studies in lower eukaryotes such as ciliates and yeast, the subject of many recent reviews. Here we concentrate on the mammalian telomere, recent progress in its study, and how recent evidence for an involvement of telomeres in the regulation of gene expression and DNA replication in yeast points to new aspects of mammalian telomere function yet to be explored. PMID- 1301132 TI - Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome. AB - We have used a series of 30 DNA probes previously mapped to the long arm of the human Y chromosome, to screen a panel of 21 patients with structural abnormalities in Yq, by genomic blot hybridisation. The results have allowed us to construct a detailed map of interval 6 of the Y chromosome, in which 28 of the probes could be assigned to 14 sub-intervals within interval 6. Some probes detect two or more loci within this region, each of which has been localised. The same set of probes has been used to screen a panel of 19 chromosomally normal azoospermic men, two of whom have been found to carry microdeletions within this region. With the completion of this map we have been able accurately to localise these microdeletions within interval 6 and show that they do not overlap. We believe these microdeletions may disrupt the azoospermia factor (AZF) involved in spermatogenesis, and which is known to lie in this region. These results are an important step towards the localisation of the AZF locus. PMID- 1301134 TI - Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice. AB - Duchenne and the less severe Becker form of muscular dystrophy (DMD,BMD) result from genetic deficiency in the level and/or activity of the protein dystrophin. The recent availability of cDNA based minigenes encoding recombinant dystrophin polypeptides has raised the possibility of somatic gene transfer as a therapeutic approach to treat dystrophin deficiency. In this respect, the mdx mouse provides a useful model of DMD exhibiting features characteristic of both the early myopathic and later fibrotic phases of the human disease. Using a mutated human cDNA, compatible in size with virus-based somatic gene transfer vectors, the pathophysiological consequences of restoring dystrophin expression have been examined in transgenic mdx mice. Transgene expression was correlated with a marked reduction of the skeletal myofibre necrosis and regeneration which is a major feature of the dystrophin-deficient phenotype in young mdx mice. The cDNA construct which is based on a very mild BMD phenotype thus encodes a highly functional dystrophin molecule whose reduced size renders it an attractive candidate for development as a therapeutic gene transfer reagent. PMID- 1301136 TI - Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III. PMID- 1301135 TI - A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa. AB - Recently it has been demonstrated that some families with autosomal dominant retinitis pigmentosa (adRP) have mutations in the rhodopsin gene while others do not. Previously we have identified six such mutations in seven adRP families in this laboratory, one of which was previously described in US patients. We now present a completed screen of the rhodopsin gene in a panel of 39 adRP families, by a rapid screening technique which will be of use for routine diagnosis. Nine different mutations were ultimately found, in a total of twelve of the 39 families. These include the six previously identified mutations, in codons 68-71, 190, 211, 255, 296 and 347, two new ones in codons 53 and 106, and another mutation first identified in a single US patient, in codon 58. Thus approximately 30% of adRP families have 'Rhodopsin RP' while the remainder probably have a defect elsewhere in the genome. Of those families in which rhodopsin mutations have been found, four have been classified D type, three as sectorial RP and the remainder are of uncertain classification. All families excluded from chromosome 3q by linkage have been classified R type. These data suggest a correlation between clinical sub-classification and the underlying rhodopsin/non-rhodopsin heterogeneity. PMID- 1301137 TI - CEB 15 detects a VNTR locus (Het: 92%) on chromosome 1p. PMID- 1301138 TI - CEB 29 detects a VNTR locus (Het: 80%) on chromosome XY. PMID- 1301139 TI - Dinucleotide repeat polymorphism at the human gene for cardiac beta-myosin heavy chain (MYH6). PMID- 1301140 TI - Dinucleotide repeat polymorphism at the human c-myc oncogene locus (MYC). PMID- 1301141 TI - Dinucleotide repeat polymorphism at the D6S223 locus. PMID- 1301142 TI - Dinucleotide repeat polymorphism in the THRA1 gene. PMID- 1301143 TI - Tetranucleotide repeat polymorphism at the D21S11 locus. PMID- 1301144 TI - A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. AB - Paragangliomas of the head and neck are slow growing tumors which rarely show malignant progression. Familial transmission has been described consistent with an autosomal dominant mode of inheritance. Clinical manifestations of hereditary paragangliomas are determined by the sex of the transmitting parent. All affected individuals have inherited the disease gene from their father, expression of the phenotype is not observed in the offspring of an affected female until subsequent transmittance of the gene through a male carrier. This finding strongly suggests that genomic imprinting is involved. We report the results of a linkage study on a large Dutch pedigree with hereditary paragangliomas. Highly significant evidence for genetic linkage to chromosome 11q23-qter with the anonymous DNA marker D11S147 was detected with a peak lod score of 6.0 at a recombination fraction theta = 0.0. Likelihood calculations yielded an odds ratio of 2.7 x 10(6) in favor of genomic imprinting versus the absence of genomic imprinting. PMID- 1301145 TI - Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. AB - The 14kb dystrophin transcript from the Duchenne muscular dystrophy (DMD) locus, which encodes a 427kDa protein, is differentially spliced at the amino terminal end giving rise to alternative transcripts expressed in muscle and brain. Here we present evidence for a 4.8kb transcript from the DMD locus which is ubiquitously expressed but is particularly abundant in Schwannoma cells where dystrophin could not be detected. The hybridisation of Western blots with dystrophin antibodies also identifies a protein of approximately 80kDa of variable abundance in different human and mdx tissues. Immunocytochemistry studies confirm the expression of this protein in nerve cells, a tissue in which full length dystrophin is not detected. Sequencing of the 5' end of a clone isolated from a rat Schwannoma cDNA library, shows that the 4.8kb transcript shares exons with the carboxy terminal end of dystrophin but the 5' untranslated region is not contained within the dystrophin transcript. We propose that the 4.8kb gene product be called apodystrophin-1 as its expression is distinct from the dystrophin 14kb mRNA but it is transcribed from the same locus. PMID- 1301147 TI - A male with two contiguous inactivation centers on a single X chromosome: study of X inactivation and XIST expression. AB - This report investigates the case of a patient with a duplication of the long arm of the X chromosome containing the putative X inactivation center (XIC) and the recently isolated XIST (X inactive-specific transcript) gene which is thought to play a role in the X inactivation process. Based on replication studies, a two fold higher than normal phosphoglycerate kinase activity and absence of XIST expression, we conclude that the duplicated region is not subject to X inactivation, despite the presence of two XICs. These results are discussed with respect to different models of X inactivation. PMID- 1301148 TI - An optimized Alu-PCR primer pair for human-specific amplification of YACs and somatic cell hybrids. PMID- 1301146 TI - Characterisation of a new rare fragile site easily confused with the fragile X. AB - A new fragile site (FRAXE) in Xq28 is described. It appears to be a typical folate sensitive fragile site. The fragile site is not associated with mental retardation, it does not give abnormal results when subjected to Southern analysis with probe pfxa3 which detects the unstable DNA sequence characteristic of fragile X syndrome. In situ hybridization mapping locates the fragile site between 150 kb and 600 kb distal to FRAXA. The distinction between the two fragile sites is important clinically since cytogenetic detection of FRAXE, without molecular analysis, could result in misdiagnosis of fragile X syndrome. PMID- 1301149 TI - Isolation and characterization of 19 dinucleotide repeat polymorphisms on chromosome 3p. AB - We have screened cosmids on chromosome 3p for (dC-dA)n.(dG-dT)n dinucleotide repeat sequences. Eighty-nine of 155 cosmids (58%) contained (dC-dA)n.(dG-dT(n repeats as determined by colony hybridization with a (dG-dT)10 oligonucleotide probe; 29 of these were subcloned and the sequences flanking the dinucleotide repeats were determined. Nineteen of the 24 loci examined for polymorphisms by PCR were found to be polymorphic with heterozygosities ranging from 3% to 86%. These dinucleotide repeat polymorphisms will be useful markers for high resolution mapping of genes that have been localized to 3p, including tumour suppressor genes associated with several types of cancer and genes responsible for various hereditary disorders, such as von Hippel-Lindau disease. PMID- 1301150 TI - Two chromosome 7 dinucleotide repeat polymorphisms at gene loci epidermal growth factor receptor (EGFR) and pro alpha 2 (I) collagen (COL1A2). PMID- 1301151 TI - Dinucleotide repeat polymorphism at the human cardiac beta-myosin heavy chain gene (HMSYHCO1) locus. PMID- 1301152 TI - A polymorphic dinucleotide repeat in intron 1 of the human tissue plasminogen activator gene. PMID- 1301153 TI - Dinucleotide repeat polymorphism at the D1S167 locus. PMID- 1301154 TI - Dinucleotide repeat polymorphism at the hormone sensitive lipase (LIPE) locus. PMID- 1301155 TI - Dinucleotide repeat polymorphism at the D15S11 locus in the Angelman/Prader-Willi region (AS/PWS) of chromosome 15. PMID- 1301156 TI - A series of hypervariable minisatellites at the D7S464 locus. PMID- 1301157 TI - Dinucleotide repeat in the human mitochondrial D-loop. PMID- 1301158 TI - A new highly polymorphic dinucleotide (CT)n repeat polymorphism D1S158 on chromosome 1q isolated by microdissection. PMID- 1301159 TI - A polymorphic dinucleotide repeat in intron 2 of the human cystatin-C gene. PMID- 1301160 TI - An autosomal homologue of the choroideremia gene colocalizes with the Usher syndrome type II locus on the distal part of chromosome 1q. AB - Employing the mouse homologue of the human choroideremia cDNA as a probe, we have identified a homologous human gene. The consensus cDNA of this gene, designated human choroideremia-like (hCHML) gene, encompasses an open reading frame of 1968 base pairs. The deduced polypeptide of hCHML displays several regions of homology to smg p25A GDI, a bovine protein known to regulate the GDP/GTP exchange of the GTP-binding protein smg p25A. hCHML is located at 1q31-qter, a chromosomal region which, by means of linkage analysis, was previously shown to carry a gene locus for Usher syndrome type II. The colocalization of hCHML and Usher syndrome type II, as well as the clinical similarities between choroideremia and Usher syndrome type II, make hCHML a candidate gene for this disorder. PMID- 1301161 TI - The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3. AB - Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb. PMID- 1301162 TI - Isolation and characterization of a novel gene with differential expression in benign and malignant human breast tumours. AB - We report the identification of a novel cDNA representing an mRNA showing significantly higher levels of expression in benign breast lesions than in carcinomas. This cDNA was identified by differential screening of a cDNA library generated from a breast carcinoma, and shows consistently higher expression in fibroadenomas than in carcinomas. The expression in both benign and malignant tissues is highest in epithelial cells as determined by in situ hybridization to tissue sections. The nucleotide sequence of the full-length cDNA has been determined, and the deduced protein is highly basic with no signal or transmembrane sequence, but two potential nuclear localization signals. Neither the DNA nor the protein sequence show any significant homology to sequences in current databases. The cDNA hybridizes to multiple sequences within both human and other mammalian genomes, but to single genomic sequences in Drosophila, Physarum and Schizosaccharomyces pombe. This cDNA therefore represents a highly conserved gene sequence. We have identified only one major transcript in human cells, and it seems likely that there are several pseudogenes within the human genome. PMID- 1301163 TI - The gene encoding the palmitoylated erythrocyte membrane protein, p55, originates at the CpG island 3' to the factor VIII gene. AB - A CpG island 30 kb 3' to the human factor VIII gene in Xq28 is associated with a 2-kb transcript. This gene encodes a previously described palmitoylated membrane protein, p55, containing a src homology motif, SH3. Although originally described in reticulocytes, the transcript is expressed in a wide variety of human tissues. The gene is also present in the mouse and expressed in all mouse tissues examined. No known factor VIII gene deletions extend into the p55 gene. Since the function of the p55 protein is not known, the p55 gene is formally a candidate for any of the 19 or more disease genes that have not been isolated but are closely linked genetically to the factor VIII gene. PMID- 1301164 TI - The organization of the intron-containing human S6 ribosomal protein (rpS6) gene and determination of its location at chromosome 9p21. AB - The intron-containing gene encoding human ribosomal protein S6 (rpS6), the major phosphoprotein in the mammalian ribosome, has been cloned. Using a PCR based cloning strategy we have isolated the rpS6 intron-containing gene in the presence of its many processed pseudogenes and determined the DNA sequence of the entire gene and its upstream and downstream flanking regions. The human rpS6 gene is 3979 bp in length and comprises six exons. Despite lacking a consensus TATA box, primer extension analysis indicates that the start of transcription is located at a single C residue within an 11 bp oligopyrimidine tract. The first exon, which contains the ATG start codon, is 48 bp in length. The DNA sequence in the 5' region of the gene has features of a CpG-rich island. Using fluorescence in situ hybridization (FISH) analysis the position of the rpS6 gene has been sublocalized to human chromosome 9p21. The similarities and differences between rpS6 and other previously characterized ribosomal protein genes are discussed. PMID- 1301165 TI - Methylation analysis of CGG sites in the CpG island of the human FMR1 gene. AB - The fragile-X syndrome of mental retardation is associated with an expansion in the number of CGG repeats present in the FMR1 gene. The repeat region is within sequences characteristic of a CpG island. Methylation of CpG dinucleotides that are 5' to the CGG repeat has been shown to occur on the inactive X chromosome of normal females and on the X chromosome of affected fragile-X males, and is correlated with silencing of the FMR1 gene. The methylation status of CpG sites 3' to the repeat and within the repeat itself has not previously been reported. We have used two methylation-sensitive restriction enzymes, AciI and Fnu4HI, to further characterize the methylation pattern of the FMR1 CpG island in normal individuals and in those carrying fragile-X mutations. Our results indicate that: (i) CpG dinucleotides on the 3' side of the CGG repeat are part of the CpG island that is methylated during inactivation of a normal X chromosome in females; (ii) the CGG repeats are also part of the CpG island and are extensively methylated as a result of normal X-chromosome inactivation; (iii) similar to normal males, unaffected fragile-X males with small CGG expansions are unmethylated in the CpG island; for affected males, the patterns of methylation are similar to those of a normal, inactive X chromosome; (iv) in contrast to the partial methylation observed for certain sites in lymphocyte DNA, complete methylation was observed in DNA from cell lines containing either a normal inactive X chromosome or a fragile-X chromosome from an affected male.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301166 TI - A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes. AB - The gene loci for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GK) map in Xp21 distal to Duchenne muscular dystrophy (DMD), and proximal to DXS28 (C7), by analysis of patient deletions. We have constructed a yeast artificial chromosome (YAC) contig encompassing a 1.2 Mb region extending distally from DMD, and containing DXS708 (JC-1), the distal junction clone of a patient with GK and DMD. A pulsed-field gel electrophoresis map of the YAC contig identified 3 potential CpG islands. Whole YAC hybridization identified cosmids both for construction of cosmid contigs, and isolation of single copy probes. Thirteen new single copy probes and DXS28 and DXS708 were hybridized on a panel of patients; the deletion mapping indicates that the YAC contig contains both GK and at least part of AHC, and together with the physical map defines a GK critical region of 50-250 kb. In one AHC patient with a cytogenetically detectable deletion we used the new probes to characterize a complex double deletion. Non-overlapping deletions observed in other unrelated AHC patients indicate that the AHC gene is large, extending over at least 200-500 kb. This mapping provides the basis for the identification of the AHC and GK genes. PMID- 1301167 TI - High-resolution in situ hybridization using DNA halo preparations. AB - To improve DNA resolution of fluorescence in situ hybridization we have adapted a nuclear extraction technique, resulting in highly extended DNA loops arranged around the nuclear matrix in a halo-like structure. In situ hybridization signals from alphoid and cosmid DNAs appear as beads-on-a-string, which, according to preliminary experiments, results from the association of individual probe fragments. By multicolor hybridizations we have been able to determine relative map position and to easily detect 10 kb overlap between individual cosmid clones, each of which shows linear beaded signals of ca. 10 microns, suggesting that the DNA is essentially linearized in our protocol. The map configuration can be typically derived from analysis of 5-10 cells only. The resolution range of the technique is at least 10-200 kb, and probably as little as a few kb, thus greatly extending the abilities of the existing FISH methodologies. This novel technique is much more efficient and practicable than pronuclei hybridizations, another method for high resolution FISH, and readily produces results with probes of a variety of genomic origin. In conclusion the DNA halo technique should be able to contribute significantly to the assessment of cosmid and YAC overlaps as well as to the sizing of gaps between adjacent contigs generated in genome projects. PMID- 1301168 TI - Multiple colors by fluorescence in situ hybridization using ratio-labelled DNA probes create a molecular karyotype. AB - Fluorescence in situ hybridization (FISH) is now widely used for the localization of genomic DNA fragments, and the identification of chromosomes by painting. We now show that half of the chromosomal complement can be painted in twelve different colors by using human chromosome specific libraries carrying three distinct labels mixed in multiple ratios. The photographs are in 'real' color rather than 'colorized'. The painting technique described here can be used for the identification of small or complex chromosomal rearrangements and marker chromosomes in humans or in any other species for which well defined chromosome specific libraries exist in a laboratory equipped with a conventional fluorescence microscope. The versatility of this novel cytogenetic technology may well constitute an advancement comparable to the introduction of chromosome banding and high resolution analysis of chromosomes in prometaphase. PMID- 1301169 TI - A yeast artificial chromosome contig spanning the Charcot-Marie-Tooth disease type 1A duplication region. AB - A contiguous set of 43 overlapping yeast artificial chromosome (YAC) clones has been developed for the Charcot-Marie-Tooth disease type 1A (CMT1A) duplication region of chromosome 17p11.2. The contig spans approximately 2.0 Mb and can be represented in a minimum of five overlapping YACs. The YAC clones were isolated from two total human genomic YAC libraries and from YAC libraries made from rodent-human hybrid cell lines. YAC clones were isolated from the libraries by polymerase chain reaction (PCR) technique. Localization to chromosome 17p11.2 was confirmed by fluorescence in situ hybridization. Overlap between the YAC clones was detected by inter-Alu PCR amplification of the YACs and by cross hybridization of the YACs with YAC insert ends obtained by Vectorette PCR. This YAC contig is a useful resource for analyzing and mapping all the genes contained within the CMT1A duplication. PMID- 1301170 TI - Construction of a physical map on mouse and human chromosome 1: comparison of 13 Mb of mouse and 11 Mb of human DNA. AB - Long range restriction site maps of 13 Mb of mouse chromosome 1 and 11 Mb of human chromosome 1 were constructed using a framework provided by a detailed mouse genetic map. Where an unambiguous gene order could be determined in both species (14 genes), the human and mouse orders were identical. In addition, the distances between markers in the mouse and human were similar except for one region of the conserved linkage group where we could detect a larger distance in the mouse compared to the human. These data support the use of comparative mapping in physical map construction and further suggest the value of using mouse genetics to help define human disease loci. PMID- 1301171 TI - Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate c-myc and the IgH locus up to several hundred kb. AB - In about 80% of Burkitt's lymphoma cases, the tumour cell harbours a reciprocal chromosomal translocation which invariably transposes the coding exons 2 and 3 of c-myc from chromosome 8 to the immunoglobulin heavy chain locus on chromosome 14. Those t(8;14) translocations which disrupt chromosome 8 within or close to the c myc gene are well documented. In this study we have focussed on t(8;14) translocations with the chromosomal breakpoint far upstream of c-myc. We analyzed the breakpoint position in 44 BL cell lines with t(8;14) translocations of different geographical origin and identified 9 cell lines with the breakpoint more than 14 kb upstream of c-myc. In these cell lines the positions of the translocation junctions on the derivative chromosomes 8q- and 14q+ were mapped by pulsed field gel electrophoresis and multicolour fluorescence in situ hybridization. The breakpoints occur at distances between 55 and more than 340 kb upstream of c-myc with no preferential site on chromosome 8. On chromosome 14, however, the translocation breakpoints are clustered in a narrow region 5' of the intron enhancer of the immunoglobulin heavy chain gene. In 7 of 9 cases, the enhancer is fused to the c-myc bearing sequences of chromosome 8. In two cases, the translocation has occurred in switch mu and downstream of C mu, respectively. The impact of these results with respect to the hypothesis, that cis-regulatory sequences from the immunoglobulin heavy chain locus can deregulate c-myc expression in a manner sufficient for tumour formation, is discussed. PMID- 1301173 TI - A serine-to-phenylalanine substitution leads to loss of alanine:glyoxylate aminotransferase catalytic activity and immunoreactivity in a patient with primary hyperoxaluria type 1. PMID- 1301172 TI - Identification of a highly polymorphic marker within intron 7 of the ALAS2 gene and suggestion of at least two loci for X-linked sideroblastic anemia. AB - We have identified a compound dinucleotide repeat within intron 7 of the human erythroid 5-aminolevulinate synthase (ALAS2) gene with a minimum of 9 alleles and heterozygosity of 78%. ALAS2 was placed on the multipoint linkage map of the X chromosome in the pericentromeric region with the locus order: pter-(DXS255, TFE3, DXS146)-(DXS14, ALAS2, DXZ1)-AR-(DXS153, DXS159)-qter. No recombination was observed between ALAS2 and the centromere marker DXZ1. As ALAS2 has recently been shown to be the defective locus in X-linked pyridoxine-responsive sideroblastic anemia (PRSA), the ALAS2 marker has allowed placement of the gene for PRSA into the multipoint linkage map of the X chromosome. With the previous exclusion of close linkage between DXS14 and sideroblastic anemia with ataxia, our data show that there are at least two loci for X-linked sideroblastic anemia. PMID- 1301174 TI - Identification of a 2 base pair nonsense mutation causing a cryptic splice site in a DMD patient. PMID- 1301175 TI - AciI and BstNI/CfrI detect all possible activating point mutations at codons 13 and 61 of the human H-ras oncogene. PMID- 1301176 TI - Two independent dinucleotide repeat polymorphisms at the D21S235 locus (21q22.1). PMID- 1301177 TI - Dinucleotide repeat polymorphisms at the D3S1246 and D3S1247 loci. PMID- 1301178 TI - Three dinucleotide repeat polymorphisms at the DXS178 locus. PMID- 1301180 TI - Dinucleotide repeat polymorphism at the D5S134 locus linked to the adenomatous polyposis coli (APC) gene. PMID- 1301179 TI - A polymorphic synonymous mutation (K54K) in the human 70 kD peroxisomal membrane protein gene (PMP1). PMID- 1301181 TI - Dinucleotide repeat polymorphism at the human ribophorin II locus (RPN2) on chromosome 20q. PMID- 1301182 TI - Dinucleotide repeat polymorphism in the human DCC gene at chromosome 18q21. PMID- 1301183 TI - Unusual variability of the complex dinucleotide repeat block at the SPN locus. PMID- 1301184 TI - Dinucleotide repeat polymorphism at the IFNA locus (9p22). PMID- 1301185 TI - Dinucleotide repeat polymorphism at the D7S547 locus. PMID- 1301186 TI - An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5' end of the monoamine oxidase A gene. PMID- 1301187 TI - Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene. AB - Mutations in the human phenylalanine hydroxylase gene producing phenylketonuria or hyperphenylalaninemia have now been identified in many patients from various ethnic groups. These mutations all exhibit a high degree of association with specific restriction fragment-length polymorphism haplotypes at the PAH locus. About 50 of these mutations are single-base substitutions, including six nonsense mutations and eight splicing mutations, with the remainder being missense mutations. One splicing mutation results in a 3 amino acid in-frame insertion. Two or 3 large deletions, 2 single codon deletions, and 2 single base deletions have been found. Twelve of the missense mutations apparently result from the methylation and subsequent deamination of highly mutagenic CpG dinucleotides. Recurrent mutation has been observed at several of these sites, producing associations with different haplotypes in different populations. About half of all missense mutations have been examined by in vitro expression analysis, and a significant correlation has been observed between residual PAH activity and disease phenotype. Since continuing advances in molecular methodologies have dramatically accelerated the rate in which new mutations are being identified and characterized, this register of mutations will be updated periodically. PMID- 1301188 TI - Partial gene duplication as a cause of human disease. AB - Tandem duplication of large regions of DNA, including duplication of whole genes, provides a substrate for genetic evolution. Tandem duplication of smaller regions involving parts of genes is now recognized as a contributor to the mutation spectrum that results in genetic disease. In this review, more than 30 unrelated partial gene duplications that have been implicated in the genesis of human genetic disease are presented and the pathogenic effects and frequency of such duplications are summarized. The mechanisms of duplication formation are analyzed with special emphasis on the molecular details of the nucleotide sequences at the duplication junctions. Evidence to date suggests that duplication may arise from either homologous (Alu-Alu) recombination or nonhomologous recombination, the latter possibly mediated by topoisomerases. For the dystrophin gene, in which most duplications have been identified, these recombination events are intrachromosomal, suggesting that unequal sister chromatid exchange is the major mechanism. PMID- 1301189 TI - A glycine250--> aspartate substitution in the alpha-subunit of hexosaminidase A causes juvenile-onset Tay-Sachs disease in a Lebanese-Canadian family. AB - The mutation causing juvenile Tay-Sachs disease (TSD) in two sibs of Lebanese Maronite origin is described. An mRNA-containing extract of cultured fibroblasts obtained from one of the probands was used as a template to amplify the coding sequence of the hexosaminidase A (Hex A) alpha-subunit. Sequencing of amplified cDNA fragments revealed a single alteration, guanine to adenine at nt 749 creating a G250D mutation. The mutation introduces a new recognition site for the restriction enzyme Eco RV, permitting identification of heterozygotes for this allele following PCR amplification and Eco RV digestion of exon 7 sequences from genomic DNA templates. In order to test the effect of this substitution, an in vitro mutagenized cDNA construct was introduced into a mammalian expression vector and transfected into monkey Cos-1 cells separately or along with a beta cDNA expression vector. When the mutant alpha-cDNA was the only gene introduced into COS cells no enzymatic activity above endogenous COS cell activity was detected. Cotransfection of normal alpha-cDNA and beta-cDNA followed by immunoprecipitation of human Hex A resulted in 20-fold increase in the ratio between positive and negative (mock transfection) control values. This allowed the detection of some residual activity (12% of the positive control) when the mutant alpha-cDNA replaced its wild-type counterpart. The predicted protein environment in which the mutation occurs is compared to that of the adult-onset Tay-Sachs disease mutation caused by a Gly269-->Ser substitution in exon 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301190 TI - Novel Tay-Sachs disease mutations from China. AB - We describe three HEXA mutations associated with infantile Tay-Sachs disease (TSD) in three unrelated nonconsanguineous Chinese families. Novel mutations were found in two of these families. The third is a previously reported mutation (G- >A transition at nt 1444) (Nakano et al., 1988). Direct sequencing of PCR products identified a novel insertion of an A after nt 547 in family 1. This change generates an early termination codon 6 bp downstream from the insertion site. Allele-specific oligonucleotide hybridization confirmed homozygosity in the proband. Single strand conformational polymorphism analysis and direct sequencing of amplified exon 13 revealed a T-->C transition at nt 1453 with the corresponding amino acid substitution W485R in the second family. This mutation creates an Fnu4HI restriction site. The proband is homozygous for this allele. When the site-specific mutagenized alpha cDNA carrying the T-->C transition at nt 1453 was expressed in COS 1 cells hexosaminidase S activity was not detectable above background. A G-->A transition at nt 1444 (exon 13) corresponding to the E482K substitution was found in the third family. This mutation occurs at a CpG dinucleotide. It has been reported in an Italian TSD proband and causes defective intracellular transport of the alpha-subunit from the rough endoplasmic reticulum to the Golgi apparatus. PMID- 1301192 TI - Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease. PMID- 1301191 TI - Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease. AB - We have determined that a man, ascertained because he fathered a child with lethal osteogenesis imperfecta (OI) with each of two partners, is mosaic in both his germline and somatic tissues for a mutation in the COL1A2 gene which encodes the pro alpha 2(I) chain of type I procollagen. His dermal fibroblasts were previously shown to synthesize a population of cysteine-containing alpha 2(I) chains that were posttranslationally overmodified. DNA sequence analysis of COL1A2 cDNAs demonstrated that the cysteine-containing chain resulted from a point mutation (G to T) in the first position of the codon for the glycine at residue 472 of the triple helical domain. Genomic DNA from the one available affected infant contained the mutant and normal COL1A2 alleles in equal proportion. Examination of DNA from several tissues of the father showed that the mutant allele was present in approximately 40% of his sperm, 80% of his lymphocytes, and nearly 100% of his dermal fibroblasts. Despite the high level of mosaicism detected in somatic tissues, the only phenotypic manifestation of OI in the proband was that he was shorter than his unaffected male relatives and had mild dentinogenesis imperfecta. Thermal stability of type I collagen molecules containing the substitution was decreased, but to a lesser extent than for a nonlethal cysteine for glycine substitution at residue 259 of alpha 2(I), indicating that this measure of molecular stability may be of limited use in explaining the pathogenesis of osteogenesis imperfecta. PMID- 1301193 TI - Five mutations at the PAH locus account for almost 90% of PKU mutations in French Canadians from eastern Quebec. PMID- 1301194 TI - A novel mutation (Arg-->Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A. PMID- 1301195 TI - Fibrillin (FBN1) mutations in Marfan syndrome. PMID- 1301196 TI - A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype. AB - Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive genetic disease caused by a deficiency of the glycosidase alpha-L-iduronidase which is required for the lysosomal degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. Patients with MPS-I store these partially degraded glycosaminoglycans in their lysosomes. MPS-I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counselling and also impedes the selection and evaluation of patients undergoing therapy such as bone marrow transplantation. We report the presence of a common mutation accounting for 31% of MPS-I alleles in a study of 64 MPS-I patients. The mutation was originally detected by chemical cleavage and then direct PCR sequencing. The mutation is a single base substitution that introduces a stop codon at position 402 (W402X) of the alpha-L iduronidase protein and is associated with an extremely severe clinical phenotype in homozygotes. Patients who are compound heterozygotes having one allele carrying the W402X mutation have a wide range of clinical phenotypes. Based on polymorphisms within the alpha-L-iduronidase gene, W402X is associated with three different haplotypes, implying that there is more than one origin for the mutation or that intragenic recombination has occurred. W402X introduces a MaeI restriction endonuclease site into MPS-I alleles enabling its simple detection, which should make possible the assessment of the efficacy of bone marrow transplantation in MPS-I patients homozygous for W402X. PMID- 1301197 TI - Prevalence of cystic fibrosis mutations in the East German population. AB - A representative multicenter cystic fibrosis (CF) mutation analysis on about half of all known cystic fibrosis patients of the 5 East German Lander is reported. Analyses for 17 mutations, among them Delta F508, R553X, G542X, S549R,N,I, G551D, S1255X, R347P,H, and Y122X, were performed. As expected, the delta F508 mutation in exon 10 of the CFTR gene is the major gene alteration causing CF in our patients. However, in comparison to studies from Western Germany, a significantly lower percentage of just over 60% is found in our patients, resembling data obtained from slavonic populations. The severe phenotype of cystic fibrosis is most frequently associated with homozygosity for the delta F508 mutation. No particular allele association could be found with the intermediate and mild phenotypes of this disease. The next most frequent of the investigated mutations is R553X (13.3% of non-delta F chromosomes) followed by R347P (9.2%) and G542X (4.4%). PMID- 1301198 TI - Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency. AB - Deficiency of cystathionine beta-synthase (CBS) causes the most common form of inherited homocystinuria. We developed a simple CBS expression system in E. coli to screen for pathogenic mutations in affected individuals. Portions of patient cDNAs were amplified by PCR and used to replace the corresponding segments of normal human CBS cDNA in the bacterial expression plasmid pHCS3. Hybrid CBS was expressed in E. coli and the segments of patient's cDNA which extinguished CBS activity were sequenced to identify the mutation. The first study of a pyridoxine responsive patient using this screen revealed that of the clones which contained either the middle or the 3'-portion of his cDNA, about half were devoid of catalytic activity. Subsequent sequencing of the affected segments confirmed a compound heterozygosity for a maternal T833-->C transition (I278T) and for a paternal A-->C transversion in the intron 11 splice acceptor. The latter mutation leads to an in-frame deletion of exon 12 (nt 1224-1358, amino acids W408 to G453). This bacterial expression system proved to be a rapid screening method for localizing pathogenic mutations in CBS, allowing us to sequence the affected portions of mutant cDNA within 7-10 days of harvesting cultured fibroblasts. PMID- 1301199 TI - A novel beta-globin structural mutant, Hb Brescia (beta 114 Leu-Pro), causing a severe beta-thalassemia intermedia phenotype. AB - This study describes a patient with a thalassemia intermedia-like phenotype in whom beta-globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T-C substitution at codon 114 of the beta-globin gene arising as a de novo mutation. The abnormal variant was designated Hb Brescia after the place of birth of the propositus. Normal sequences were detected at the in trans beta-globin locus. In addition, alpha-globin gene analysis detected a triple alpha-globin locus which was inherited from the father. The T-C change at position 114 of the beta-globin gene results in a leucine to proline substitution (Leu-Pro) in the G helix. The resulting Hb tetramer is highly unstable and precipitates forming inclusion bodies in the peripheral red blood cells. Moreover, the Leu-Pro substitution interferes negatively with the four alpha 1 beta 1 contact points of the G-helix most likely adversely affecting the alpha beta dimer formation. The very severe phenotype presented by our patient is unusual in a heterozygote for an unstable Hb variant and may be explained by the coinheritance of the triple alpha-globin locus. PMID- 1301200 TI - Two missense mutations causing mild hyperphenylalaninemia associated with DNA haplotype 12. AB - The genetic defects responsible for most phenylketonuria (PKU) and hyperphenylalaninemia (HPA) cases are located in the phenylalanine hydroxylase (PAH) gene. Approximately 50-60 mutations have been reported in Caucasians and are reflected in a wide range of clinical severities. Most mutations are linked to specific haplotypes, as defined by eight polymorphic restriction sites in the PAH gene. We hypothesized that there is at least one mild mutation linked to haplotype 12 in the Swedish PKU/HPA population, since 7 of 8 patients carrying haplotype 12 had mild HPA. Sequence analysis revealed a C-to-G transversion at the second base of codon 322, resulting in a substitution of glycine for alanine, in four mutant haplotype 12 genes, and a G-to-A transition at the second base of codon 408, resulting in a substitution of glutamine for arginine, in another three mutant haplotype 12 genes. These mutations segregated with mutant haplotype 12 alleles in nuclear families but were not present on normal or other mutant alleles. Both mutations were tested in a eukaryotic expression system in which enzyme activities of different mutant PAH enzymes reflect the relative severities of the mutations, although these in vitro activities cannot be translated directly into in vivo hepatic activities. The A322G mutant PAH had about 75% and the R408Q mutant PAH about 55% of the wild-type PAH enzyme activity. These in vitro activities are the highest reported for mutant PAH enzymes produced in the same expression system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301201 TI - In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus. AB - Mutations at the phenylalanine hydroxylase (PAH) locus are the major cause of hyperphenylalaninemia. We have previously described four mutations (M1V, IVS12nt1, R408W, and S349P) at the PAH locus in French Canadians with ancestry in eastern Quebec. Here we report (1) identification of another mutation, on a haplotype 9 chromosome, which converts codon 65 from isoleucine (ATT) to threonine (ACT), (2) expression analysis of the I65T mutation in COS cells demonstrating 75% loss of both immunoreactive protein and enzyme activity, and (3) expression analysis of the most prevalent PKU allele (M1V) in eastern Quebec, showing nondetectable levels of PAH protein and activity, a finding compatible with a mutation in the translation initiation codon. Homozygosity for M1V and codominant inheritance of I65T/R408W were both associated with classical phenylketonuria. PMID- 1301202 TI - Illegitimate transcription of phenylalanine hydroxylase for detection of mutations in patients with phenylketonuria. AB - Illegitimately transcribed phenylalanine hydroxylase mRNA was amplified using the polymerase chain reaction from both fibroblasts and Epstein-Barr virus transformed lymphocytes. This method was used to study mutations of this gene in patients with phenylketonuria and known point mutations were easily detected. Illegitimate transcription was successful for studying splicing defects and it was found that the previously described mutation which changes G to A at the 5' donor site of intron 7 causes exon 7 to be spliced out. PMID- 1301203 TI - Trapped-oligonucleotide nucleotide incorporation (TONI) assay, a simple method for screening point mutations. AB - We present a simple screening method for detecting a known point mutation, using only one 5'-biotinylated oligonucleotide primer, with its 3' end adjacent to the mutation site. In parallel reactions, an amplified DNA template encompassing the biotinylated oligonucleotide and mutation site undergoes 40 step-cycles of single nucleotide incorporation using Taq thermostable DNA polymerase and only one radioactive [alpha-32P]dNTP, specified by either the normal or mutant sequence. The oligonucleotides, now radioactively labelled at the 3' end according to the template sequence, are then trapped by streptavidin-coated magnetic beads, and the percent of radiolabel incorporated is determined directly by the Cerenkov method in a scintillation counter. The trapped-oligonucleotide nucleotide incorporation (TONI) assay has been used for the screening of a mitochondrial polymorphism, and has also been shown to distinguish the genotypes of hemoglobin A/C, A/A, A/S, and S/S. It is reproducible over at least a 100-fold range of radioisotope and a 10-fold range of oligonucleotide primer. This method is particularly useful for diagnosing mutations which do not produce alterations detectable by restriction enzyme analysis, since optimization of conditions is rarely necessary. In addition, it requires only a single oligonucleotide, and no electrophoretic separation of the allele-specific products. It thus represents an improved and simplified modification of the existing allele-specific primer extension methods (Kuppuswamy et al., Proc Natl Acad Sci USA 88:1143-1147, 1991; Sokolov, Nucl Acids Res 18:3671, 1989; Syvanen et al., Genomics 8:684-692, 1990). PMID- 1301204 TI - A novel delta-thalassemia mutation A G-->C substitution at codon 30 of the delta globin gene in a person of southern Italian origin. PMID- 1301205 TI - Frameshift duplication resulting in truncated dystrophin in a patient with Duchenne muscular dystrophy. PMID- 1301206 TI - The unstable and methylatable mutations causing the fragile X syndrome. PMID- 1301207 TI - Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene. AB - We present an update on mutations and polymorphisms in the human X chromosome located pyruvate dehydrogenase E1 alpha gene. A total of 20 different mutations are tabulated. The mutations include deletions, insertions, and point mutations. Certain sequences seem particularly prone to mutation. Most of the mutations are found in exons 10 and 11. Furthermore, four of the mutations are seen in unrelated patients. Little is known about how the mutations affect the structure or function of the pyruvate dehydrogenase complex. PMID- 1301208 TI - Plant endogenous beta-glucuronidase activity: how to avoid interference with the use of the E. coli beta-glucuronidase as a reporter gene in transgenic plants. AB - We have detected a plant beta-glucuronidase activity, present in several tissues and organs of plant species belonging to different families. The fluorimetric beta-glucuronidase assay was used to partially characterize this activity in post ribosomal supernatants of tobacco leaves. The tobacco activity is very stable at low temperatures, but quickly inactivated above 45 degrees C. It is relatively resistant to proteases and insensitive to -SH group reagents and to ionic conditions. It does not require, nor is it inhibited by, divalent cations. Although these properties are shared by the Escherichia coli beta-glucuronidase, the two activities can be distinguished by: (i) their different sensitivity to the specific inhibitor saccharic acid-1,4-lactone; (ii) their different thermal stability (iii) their different pH optima (5.0 for the plant activity and close to neutral for the bacterial enzyme). Therefore, under appropriate experimental conditions, it should be possible to assay the E. coli beta-glucuronidase in transgenic plants without interference from the endogenous plant activity. PMID- 1301209 TI - Coexpression of the cys E and cys M genes of Salmonella typhimurium in mammalian cells: a step towards establishing cysteine biosynthesis in sheep by transgenesis. AB - The Salmonella typhimurium genes for serine acetyltransferase (cys E) and O acetylserine sulphydrylase B (cys M) were isolated and characterized in order to express these as transgenes in sheep to establish a cysteine biosynthesis pathway and, thereby, to achieve an increased rate of wool growth. Comparison of the S. typhimurium and Escherichia coli genes showed considerable homology, both at the nucleotide and amino acid sequence levels. The in vitro and in vivo expression studies showed that both genes could be transcribed and translated in eukaryotic cells and that their products could function as active enzymes. The cys M gene of S. typhimurium possessed a GUG initiation codon, like its E. coli counterpart, but translation could be initiated using this codon in eukaryotic cells to give an active enzyme product. Chinese hamster ovary cells, stably transfected with a tandem arrangement of the two genes, showed a capacity to synthesize cysteine in vivo, indicating the establishment of a cysteine biosynthesis pathway in these cells. The measured levels of activity of the gene products suggest that improved wool growth is possible by transgenesis of sheep with these genes. PMID- 1301210 TI - High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I. AB - To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5' flanking sequence and 1 kbp of its 3' flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein A-I, high density lipoprotein cholesterol and phospholipid than sera from non transgenic littermates. Transgenic rats expressing high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects of increased apolipoprotein A-I production on lipid and lipoprotein metabolism. PMID- 1301212 TI - Pollen-specific expression of the Arabidopsis thaliana alpha 1-tubulin promoter assayed by beta-glucuronidase, chloramphenicol acetyltransferase and diphtheria toxin reporter genes. AB - We have characterized the promoter specificity of the Arabidopsis thaliana alpha 1-tubulin (alpha 1-tub) gene by studying expression patterns of gene fusions between the 2.2 kbp 5' upstream region of the alpha 1-tub gene and each of three different reporters: chloramphenical acetyltransferase, beta-glucuronidase or the diphtheria toxin chain A gene. Analysis of transgenic tobacco and Arabidopsis plants carrying the transgene showed that the chloramphenicol acetyltransferase and beta-glucuronidase activities were not detected in any vegetative or reproductive organs except mature pollen. Transgenic tobacco plants carrying the diphtheria toxin chain A gene under the control of the alpha 1-tub promoter were of normal phenotype but seed fertility was drastically reduced. Furthermore, the transgene could not be transmitted to the next generation through pollen, supporting the observation that the alpha 1-tub promoter is active only in pollen. It was observed that the promoter activity was most active in mature pollen and decreased significantly during in vitro pollen germination, indicating that the promoter is inactive or subdued in germinating pollen. The promoter activity was not affected by various plant growth hormones during pollen maturation. PMID- 1301211 TI - Impaired expression of chimaeric major histocompatibility complex transgenes associated with plasmid sequences. AB - Plasmid vector sequences were retained (vector+), or removed (vector-) from hybrid major histocompatibility complex gene constructs prior to microinjection of fertilized ova for the production of transgenic mice. In transgenic mice containing integrated vector+ gene constructs, low levels of class II cell surface determinants were detected on splenocytes from only two out of six independent lines. Class II membrane determinants were not detectable on splenocytes from the remaining four vector+ transgenic lines. Expression of transgene products did not correlate with transgene copy number which ranged from 1-10 copies. Low levels of mRNA transcripts were detected in thymic mRNA from vector+ lines. In contrast, high levels of thymic and splenic mRNA transcripts were detected in offspring from all four vector- transgenic lines. Spleen cells from the vector- transgenic animals also expressed high levels of the hybrid major histocompatibility complex transgene products. These results implicate plasmid vector sequences in the inhibition of expression of the hybrid class II class I major histocompatibility complex genes in transgenic mice. This putative inhibition of transgene expression presumably occurs at the level of gene transcription. PMID- 1301213 TI - Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes. AB - The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated by the use of labelled ovine prolactin) was increased 2-3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice. PMID- 1301214 TI - Synthetic cryIIIA gene from Bacillus thuringiensis improved for high expression in plants. AB - A 1974 bp synthetic gene was constructed from chemically synthesized oligonucleotides in order to improve transgenic protein expression of the cryIIIA gene from Bacillus thuringiensis var. tenebrionis in transgenic tobacco. The crystal toxin genes (cry) from B. thuringiensis are difficult to express in plants even when under the control of efficient plant regulatory sequences. We identified and eliminated five classes of sequence found throughout the cryIIIA gene that mimic eukaryotic processing signals and which may be responsible for the low levels of transcription and translation. Furthermore, the GC content of the gene was raised from 36% to 49% and the codon usage was changed to be more plant-like. When the synthetic gene was placed behind the cauliflower mosaic virus 35S promoter and the alfalfa mosaic virus translational enhancer, up to 0.6% of the total protein in transgenic tobacco plants was cryIIIA as measured from immunoblot analysis. Bioassay data using potato beetle larvae confirmed this estimate. PMID- 1301215 TI - Biosafety of kanamycin-resistant transgenic plants. AB - Kanamycin resistance is one of the most frequently used selection markers for obtaining transgenic plants. The introduction of these transgenic plants into agricultural practice will cause the kanamycin resistance gene and the gene product to be present on a large scale. The desirability of this situation is analysed. The nature, properties and applications of the antibiotic kanamycin are briefly reviewed, as are the mechanisms of kanamycin resistance. It is argued that the gene used for resistance is an excellent choice because of the high substrate specificity of the enzyme encoded. Human or veterinary antibiotic therapies will not be compromised. Also, the physico-chemical characteristics of the antibiotic exclude the existence of selective conditions in the environment. Therefore, a transgenic plant or any other organism that might have acquired the gene will not get any selective advantage because of this gene. Evidence further suggests there is no toxicity or predictable harm of both gene or gene product for human or animal consumption. Full legislative clearance of this transgenic trait is therefore acceptable. PMID- 1301216 TI - Tissue partitioning of cadmium in transgenic tobacco seedlings and field grown plants expressing the mouse metallothionein I gene. AB - Since agricultural crops contribute > 70% of human cadmium (Cd) intake, modification of crops to reduce accumulation of this pollutant metal during plant growth is desirable. Here we describe Cd accumulation characteristics of seedlings and field grown tobacco plants expressing the Cd-chelating protein, mouse metallothionein I. The objective of the transformation is to entrap Cd in roots as Cd-metallothionein and thereby reduce its accumulation in the shoot. Transformed and control seedlings were exposed for 15 days in liquid culture at a field soil-solution-like Cd concentration of 0.02 microM. Transformed seedlings of Nicotiana tabacum cultivar KY 14 contained about 24% lower Cd concentration in shoots and about 5% higher Cd concentration in roots than control seedlings. Dry weights of transformed and control tissues did not differ significantly. In the field in 1990, mature transformed N. tabacum cv. KY 14 plants exposed only to endogenous soil Cd contained about 14% lower leaf lamina Cd concentration than did controls. Differences were significant at the p < or = 0.1 level in 13 of 16 leaf positions. Leaf dry weight did not differ significantly but transformed field plants had 12% fewer leaves and were 9% shorter than the controls. Copper (Cu) concentration was significantly higher (ca10%) in the bottom nine leaf positions of transformed plants suggesting that reduced leaf number and plant height may be due to Cu deficiency or toxicity. Alternatively, somaclonal variation or gene position effects may be involved. No differences were found in zinc levels. With N. tabacum cv. Petit Havana, transformed seedlings contained no less Cd in shoots but 48% higher Cd concentration in roots.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301217 TI - Gallstones and laparoscopic cholecystectomy. AB - The National Institutes of Health Consensus Development Conference on Gallstones and Laparoscopic Cholecystectomy brought together surgeons, endoscopists, hepatologists, gastroenterologists, internists, radiologists, and epidemiologists as well as other health care professionals and the public to address (1) the indications for treatment of patients with gallstones; (2) the role of laparoscopic cholecystectomy in treating patients with gallstones; (3) the role of alternative medical and surgical treatments for gallstones; (4) the comparative results of laparoscopic cholecystectomy with open cholecystectomy and other available treatments; (5) techniques for detecting and treating bile duct stones with or without laparoscopic cholecystectomy; and (6) future directions for research in prevention and management of gallstone disease and in laparoscopic cholecystectomy. Following 2 days of presentations by experts and extensive discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel concluded that (1) most patients who experience symptoms of gallstones should be treated; (2) in comparison with open cholecystectomy, laparoscopic cholecystectomy provides a safe and effective treatment for most patients with symptomatic gallstones and has become the treatment of choice for many patients; (3) patients who are not good candidates for laparoscopic cholecystectomy include those with generalized peritonitis, septic shock from cholangitis, severe acute pancreatitis, endstage cirrhosis, and gallbladder cancer; (4) laparoscopic cholecystectomy decreases pain and disability without increasing mortality and morbidity and can be performed at an equal or lower cost than open cholecystectomy; and (5) every effort should be made to ensure that surgeons performing laparoscopic cholecystectomy are properly trained and credentialed. The full text of the consensus panel's statement follows. PMID- 1301218 TI - [Jean Roche (1901-1992)]. PMID- 1301219 TI - [Normal sexual differentiation: molecular genetic and endocrinology]. AB - Analysis of the sexual determination and differentiation factors has progressed by the important findings made in biochemistry (hormonal assays, determination of the receptor concentration), in cellular and molecular endocrinology (mechanism of the hormonal action) and in genetics (identification, isolation and cloning of the genes implied in the sexual determination and differentiation pathways). We first describe the basis of sexual determination and differentiation, and then we analyze the different roles of SRY gene, encoding for the testis determining factor, androgen receptor gene, 5 alpha-reductase gene and anti-Mullerian hormone gene. PMID- 1301220 TI - [Chronic cardiac insufficiency, a disease of adaptation]. AB - Cardiac hypertrophy due to a mechanical overload is not a disease per se but the physiological reaction of the heart to a disease which is usually arterial hypertension and/or coronary insufficiency. It results from the put into play of several changes in gene expression, frequently species-specific, which explain the thermodynamic improvement of the cardiac function and the physiological adaptation of the heart to the new environmental requirements. Some of these modifications can have detrimental consequences and explain the modifications of ventricular compliance and the high incidence of arrhythmias in ventricular hypertrophy. The most important changes in the genetic expression which have been reported so far after pressure overload are located on contractile proteins and on membrane proteins. PMID- 1301221 TI - [Elastin and arteriosclerosis: determination and characterization of elastin peptides in blood]. AB - During pathologies such as arteriosclerosis and emphysema, degradation of elastin by elastases occurs and elastin peptides are produced. In order to evaluate elastin degradation, measurements of elastin peptide concentration in human blood were carried out. According to elastin peptides used for obtention of antibodies and for ELISA, the measured values are different. Elastin peptides have several biological effects: they are chemotactic, modify ion fluxes and several intracellular mechanisms. PMID- 1301222 TI - [Molecular pathology of Duchenne and Becker muscular dystrophy]. AB - Duchenne and Becker muscular dystrophies (DMD and BMD) are two allelic recessive X-linked disorders. Molecular deletions of various regions of the dystrophin gene are the main mutations detected in DMD and BMD patients. Molecular study of DMD and BMD DNA are instrumental to understand the pathological molecular mechanisms and the function of the protein. We describe here dystrophin and its interaction with a glycoprotein complex and we then focus on two particular patients with partial deletions of the dystrophin gene: 1) a typical Becker patient, who shows an intragenic deletion disrupting the reading frame. We describe in this case alternative splicings restoring the reading frame, which might explain the mild clinical phenotype of this patient, 2) a deletion of the distal part of the DMD gene coding for the carboxyterminal domain of the dystrophin in a young patient. The normal localization of dystrophin at the inner face of the plasma membrane in the muscle of this patient suggests that the last domain of this protein is not sufficient to anchor dystrophin at the membrane. PMID- 1301223 TI - [Molecular genetics of growth hormone resistance syndrome]. AB - The cloning of a putative growth hormone receptor (GH-R) cDNA has opened new approaches for the understanding of the molecular basis of GH insensitivity in humans. This molecule belongs to a new class of transmembrane receptors including prolactin, granulocyte-macrophage colony stimulating factor, erythropoietin and some interleukin receptors. Although the domains responsible for signal transduction have not yet been identified, the molecular study of a GH-resistance syndrome described by Laron et al. should provide insight into the structure function relationships of the GH-R and related receptors. This autosomal recessive disorder is characterized by very low serum levels of Insulin-Like Growth Factor I (IGF-I), despite increased secretion of GH with normal activity. Two approaches can be used to test the involvement of the GH-R in this syndrome. The first one, which is indirect, is performed through linkage analysis between GH-R and Laron phenotype; this allowed us to incriminate the GR-R gene in this syndrome. The second approach consists in the identification of molecular defects in the GH-R gene of patients with Laron syndrome; this allowed the detection of a partial gene deletion and different point mutations. The short stature of the Pygmee population could be related to the Laron syndrome because individuals from this population are also resistant to GH therapy. Therefore, it seems interesting to search for molecular variations of the GH-R gene in this population. Nevertheless, preliminary results indicate that the GH-R gene is not directly involved in this particular short stature condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301224 TI - [Pathology of unstable sequence of genome: fragile-X-syndrome]. AB - Fragile X syndrome is the most frequent form of inherited mental retardation and is associated with a fragile site at Xq27-3. This fragile site is an unstable microsatellite repeat, p(CCG). In fragile X syndrome families, this sequence exhibits variable amplification, the length of which correlates with phenotype. Affected persons have both a "full mutation" and abnormal DNA methylation. Subjects with smaller increase of this sequence, called "premutation", have little or no risk retardation, but are at high risk of having affected children or grandchildren. The passage from "premutation" to "full mutation" status occurs only with transmission from the mother. The unusual segregation patterns in fragile X pedigrees is referred to as the Sherman paradox, now elucidated by genotypic analysis. We present here a brief review of this pathology and illustrate the use of this new diagnostic test in our laboratory. PMID- 1301225 TI - [Illegitimate transcription: discovery and application to gene molecular pathology]. AB - In 1988, by using the powerful cDNA/PCR technique, it was demonstrated that there are very low levels of dystrophin mRNA in a variety of non-muscle tissues, including cultured fibroblasts and lymphoblastoid cell lines. The phenomenon was also shown for a number of other tissue-specific gene, including beta-globin, factors VIIIc and IX, anti-mullerian hormone, L-pyruvate kinase, retinal blue pigment, phenylalanine hydroxylase. The level of transcript in inappropriate cells is exceedingly low, perhaps one mRNA per 100-1,000 cells. This low-level ubiquitous transcription of tissue-specific genes was called "illegitimate" or "ectopic" transcription, and has been proven to occur for 17 gene transcripts to date. The mechanism and biological significance of illegitimate transcription are still obscure, but, since illegitimate transcripts exhibit the same pathology as legitimate transcripts, they have been useful tool in the study of already 9 inherited diseases. This strategy will be applied widely for diseases where samples from the appropriate tissue for study is difficult to obtain, or where an mRNA is easier or more informative to study than a genomic DNA (as for large genes, or where alternative splicings is involved). PMID- 1301226 TI - [Cytotoxic response against human immunodeficiency virus (HIV): control with suppressor factor]. AB - We report a new suppressor function of CD8+ CD57+ lymphocytes from HIV seropositive patients recipients, on the cytolytic activity of allospecific CTL, NK and LAK cells. This inhibitory effect is mediated by a non-antigen specific soluble factor distinct from PGE2, TGF beta and TNF alpha and beta. Biochemical characterization indicates that the CD8+ CD57+ inhibitory activity: 1) is heat and trypsin resistant but remains sensitive to pronase E hydrolyse, 2) specifically bind to concanavalin A-sepharose column, 3) is mediated by a 20-30 kdaltons glycoprotein. PMID- 1301227 TI - [In vivo and in vitro antitumoral effects of an extract from Vibrio cholerae in different murine models. I. Effect in vivo of bacterial extract from Vibrio cholerae on the development of different murine tumoral grafts]. AB - A bacterial extract from Vibrio cholerae, so called DGZ, is shown to prevent transplantation of sarcoma 180 and Lewis lung carcinoma. A 4 days DGZ treatment (4 x 100 micrograms) triggers reject of the graft by 40% of the mice. The mice which have rejected a graft once after treatment, cannot be grafted lately or, at least, the tumor growth is delayed. The association with cisplatinum (4 x 25 micrograms) allows to protect 90 to 95% of the mice. PMID- 1301228 TI - [Development of a technique for the complete correction of transposition of great vessels]. AB - Complete transposition of the great arteries is one of the most common cardiovascular anomalies. Several surgical methods of treatment have been proposed. Arterial repair theoretically seems a better option since it does not introduce any additional intra cardiac anomaly and it restores the left ventricle to its natival systemic function. The rationale for neonatal arterial repair lies on fetal and neonatal cardiopulmonary physiology. The left ventricle has to eject immediately after surgery a normal cardiac output at systemic pressure in the aorta. This is the case in the neonatal period, because during fetal life pulmonary artery and aortic pressure are equal. For simple TGA, after birth, with the fall in pulmonary vascular resistances and constriction of the ductus arteriosus, pulmonary artery and left ventricular pressures drop dramatically to less than one third (1/3) of systemic pressure. As a result, the left ventricle is not stimulated for growth adaptation and becomes a thin ventricle less contractile and more compliant. However, there is little doubt that during the first 2 to 4 post-natal weeks, the left ventricle is still suitable to sustain a systemic workload. Between april 1984 and april 1992, four hundred and twenty six (426) consecutive neonates underwent an arterial switch operation for various forms of transposition: with 34 hospital deaths. The mean age at operation was 13 days and the mean weight was 3.2 kg. Among patients with TGA-VSD and coarctation, 14 underwent a single stage repair through mid sternotomy. Actuarial survival rates were: 89% for TGA-IVS at 5 years, 90% for TGA-VSD, 85.3% for TGA-VSD and coarctation at 3 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301229 TI - [HDL and reverse cholesterol transport. Role of cholesterol ester transfer protein]. AB - As most of peripheral cells are not able to catabolize cholesterol, the transport of cholesterol excess from peripheral tissues back to the liver, namely "reverse cholesterol transport", is the only way by which cholesterol homeostasis is maintained in vivo. Reverse cholesterol transport pathway can be divided in three major steps: 1) uptake of cellular cholesterol by the high density lipoproteins (HDL), 2) esterification of HDL cholesterol by the lecithin: cholesterol acyltransferase and 3) captation of HDL cholesteryl esters by the liver where cholesterol can be metabolized and excreted in the bile. In several species, including man, cholesteryl esters in HDL can also follow an alternative pathway which consists in their transfer from HDL to very low density (VLDL) and low density (LDL) lipoproteins. The transfer of cholesteryl esters to LDL, catalyzed by the Cholesteryl Ester Transfer Protein (CETP), might affect either favorably or unfavorably the reverse cholesterol transport pathway, depending on whether LDL are finally taken up by the liver or by peripheral tissues, respectively. In order to understand precisely the implication of CETP in reverse cholesterol transport, it is essential to determine its role in HDL metabolism, to know the potential regulation of its activity and to identify the mechanism by which it interacts with lipoprotein substrates. Results from recent studies have demonstrated that CETP can promote the size redistribution of HDL particles. This may be an important process in the reverse cholesterol transport pathway as HDL particles with various sizes have been shown to differ in their ability to promote cholesterol efflux from peripheral cells and to interact with lecithin: cholesterol acyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301230 TI - [Liposomes or HDL and phospholipid transfer to adrenocortical cells in culture]. PMID- 1301231 TI - Blood pressure and heart rate response to vasoactive agents in conscious diabetic rats. AB - Blood pressure and heart rate responses to different vasoactive agents were observed in conscious streptozotocin-diabetic rats. An indwelling femoral artery catheter was used for direct measurement of arterial pressure and heart rate. The femoral vein was cannulated for drug administration. In a resting state diabetic rats showed lower heart rates and lower systolic blood pressure. The vasodepressor response to both acetylcholine and sodium nitroprusside was decreased, while the heart rate increase induced by the baroreceptor reflex was not altered. Both the increase in blood pressure and the reflex bradycardia to norepinephrine were decreased in the diabetic group. When the change in heart rate was plotted against blood pressure in response to norepinephrine, there was no difference in the two groups of animals. The vasodepressor response to isoproterenol, hydralazine, and verapamil in diabetic rats was unchanged. The results demonstrate a decreased vascular responsiveness in diabetic rats to norepinephrine, acetylcholine, and nitroprusside. The diabetes-induced vascular system changes require further study to understand the mechanisms involved. PMID- 1301233 TI - Modification of the renal response to endopeptidase inhibition and atrial natriuretic peptide infusion in normal dogs. AB - Inhibition of intrarenal neutral endopeptidase 24:11 (NEP) increases the natriuretic response to infused atrial natriuretic peptide (ANP). In various models of canine heart failure, angiotensin and kinins have been shown to modulate ANP and (or) NEP activity. In the present study, we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery (or by denervating the left kidney) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 (a potent NEP inhibitor) and ANP (75 ng.kg 1.min-1). Four dogs received angiotensin (1.5 ng.kg-1.min-1) into the left renal artery, 8 dogs received saralasin (5 micrograms/min), 5 dogs received noradrenaline (2 micrograms/min), and 6 dogs received bradykinin (3 micrograms/min). Five dogs underwent left renal denervation. Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP. Saralasin augmented the natriuretic response. None of the other protocols influenced sodium excretion. We conclude that angiotensin may modulate either the enzymatic degradation of ANP or influence its renal tubular effects. PMID- 1301232 TI - Hemodynamic and plasma atrial natriuretic factor responses to cardiac volume loading in young versus older normotensive humans. AB - To assess the effects of age on responsiveness of atrial natriuretic factor (ANF) release, and the possible contribution of cardiac sympathetic activity, in young (n = 8) and older normotensives (n = 7), the effects of cardiac volume load on plasma ANF, central venous pressure, and general hemodynamics were evaluated. Studies were performed after pretreatment with placebo or 80 mg propranolol. Cardiac volume loading increased central venous pressure by 3-5 mmHg (1 mmHg = 133.3 Pa); beta-blockade did not affect this response. Cardiac volume load caused significant increases in heart rate (10-15 beats/min) and cardiac index (by 0.7 0.8 L.min-1.m-2) and decreases in plasma catecholamines. Propranolol attenuated the increases in heart rate and cardiac index. These hemodynamic responses did not differ significantly between the two groups of subjects. Cardiac volume load significantly increased plasma ANF, by 87 +/- 21 pg/mL in the young normotensives and by 212 +/- 33 pg/mL in the older normotensives (p < 0.01, young vs. older). beta-Blockade did not affect this different response. Our results show that the plasma ANF response to volume loading is potentiated by aging. Although differences in atrial stretch cannot be excluded, this effect may relate to the decrease in clearance of plasma ANF occurring with aging. PMID- 1301234 TI - Calcitonin gene related peptide relaxes cholecystokinin-induced contraction in guinea pig gallbladder strips in vitro. AB - Calcitonin gene related peptide has been shown to relax vascular and intestinal smooth muscle. This study examines the effects of calcitonin gene related peptide on cholecystokinin-induced contraction of guinea pig gallbladder strips in vitro. Calcitonin gene related peptide was found to cause a dose-dependent relaxation of cholecystokinin-induced tension, which was blocked by the calcitonin gene related peptide receptor antagonist human calcitonin gene related peptide. Previous studies demonstrated that calcitonin gene related peptide acted directly on guinea pig gallbladder smooth muscle to inhibit acetylcholine- or KCl-induced contraction. The present results further confirm that calcitonin gene related peptide acts directly on the smooth muscle. In addition, the use of L-NG nitroarginine methyl ester, glibenclamide, and other agents strongly suggests that calcitonin gene related peptide also acts by way of the nonadrenergic noncholinergic nervous system, to induce the relaxation of cholecystokinin induced contraction observed in the guinea pig gallbladder strips. PMID- 1301235 TI - Changes in blood flow distribution during the perinatal period in fetal sheep and lambs. AB - We have measured total blood flows and blood flows per 100 g tissue to major tissues at 120 and 140 days gestation in fetal sheep and at 3 and 21 days of age in lambs (gestation period = 144 +/- 2 days). Between 120 and 140 days gestation, flow per 100 g tissue increased by 74, 150, and 317% in the renal, intestinal, and hepatic arterial beds, but no further significant change in flow was observed at 3 or 21 days postpartum. Blood flows per 100 g to cerebral hemispheres and cerebellar tissues also increased dramatically during late gestation (142 and 121%, respectively), but declined sharply by 3 days postpartum (73 and 75%, respectively). Brain blood flows at 21 days postpartum remained substantially below late gestational levels. Adrenal blood flows per 100 g more than doubled during late gestation, fell by more than half at birth, and only partially recovered by 21 days of age. Blood flows to carcass tissues did not change in late gestation, fell at birth, then partially recovered. Pre- and post-natal increases in brain blood flows were almost entirely attributable to increased perfusion rather than tissue growth, whereas large perinatal increases in flow to the diaphragm paralleled tissue growth. Tissue growth and increased perfusion per 100 g contributed almost equally to increased blood flows to kidneys postnatally, and to adrenal glands and the gastrointestinal tract prenatally. PMID- 1301236 TI - Effects of fructose loading in streptozotocin-diabetic and nondiabetic rats. AB - The present study compares the cardiovascular consequences of a 6-week fructose feeding in nondiabetic and streptozotocin-diabetic rats. Myocardial performance of these animals was determined using the isolated perfused working heart preparation. Systolic blood pressure, pulse rate, ventricular weight/body weight ratio, and plasma levels of glucose, insulin, triglycerides, and cholesterol were measured. In nondiabetic rats, fructose drinking caused significant increases in blood pressure, pulse rate, and plasma concentrations of insulin and triglycerides. Streptozotocin-diabetic animals exhibited significantly less body weight growth, slower pulse rate, higher plasma levels of cholesterol and triglycerides, ventricular enlargement, and functional impairment of the myocardium. The fructose-loaded diabetic rats had larger increases in plasma cholesterol and triglycerides than did control fructose-fed rats, but the fructose-induced increases in blood pressure and pulse rate were attenuated significantly. However, plasma levels of glucose and insulin and the degree of ventricular enlargement and myocardial dysfunction were not significantly different from those of control diabetic rats. These results show that fructose loading for 6 weeks can cause increases in blood pressure, pulse rate, and plasma lipids in both nondiabetic and diabetic rats. However, fructose ingestion does not significantly alter glycemic control or affect the development of myocardial dysfunction in streptozotocin-diabetic rats. PMID- 1301237 TI - Interleukin-1 receptor antagonist: effectiveness against interleukin-1 fever. AB - Conscious cats were used to examine the effectiveness of the interleukin-1 receptor antagonist against the fever induced by interleukin-1 and endotoxin. Although inactive by itself, the antagonist (three 1-micrograms bolus injections at 10-min intervals), injected into the third ventricle, attenuated the febrile response to a subsequent intracerebroventricular bolus of interleukin-1. The rise in prostaglandin E2 levels in cerebrospinal fluid, which is a characteristic feature of fever, was curtailed as well. The interleukin-1 antagonist had little or no inhibitory effect on the response to an intracerebroventricular bolus of endotoxin, even though a higher dose was employed (2-micrograms bolus injections given three times at 10-min intervals and six times at 30-min intervals, respectively, before and after endotoxin administration). At either dosage, the intracerebroventricular antagonist was completely ineffective against an intravenous bolus injection of interleukin-1 or endotoxin and both fever and prostaglandin E2 elevation developed unabated. We conclude that brain receptors mediating the pyrogenic action of centrally injected interleukin-1 are susceptible to the antagonist. The same receptors, however, are seemingly not activated by systemic pyrogens. Our findings are consistent with the concept of circulating interleukin-1 acting outside the blood-brain barrier in the normal sequence of fever. PMID- 1301238 TI - Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity. AB - Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775 1100 microns from the pial surface, discharged in a burst-pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5-15 min of the injection. The basic pattern of burst-pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5 HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation. PMID- 1301239 TI - Dose-dependent, mechanism-based inactivation of cytochrome P450 monooxygenases in vivo by 1-aminobenzotriazole in liver, lung, and kidney of untreated, phenobarbital-treated, and beta-naphthoflavone-treated guinea pigs. AB - The mechanism-based inactivation of the cytochrome P450 (P450) dependent monooxygenase system was studied in vivo in liver, lung, and kidney of untreated, phenobarbital-treated, and beta-naphthoflavone-treated guinea pigs 24 h after administration of 1-aminobenzotriazole (1-100 mg/kg, i.p.). Microsomal isozyme selective or -specific monooxygenase activities were inhibited in a dose dependent manner in all three organs. In the liver of untreated and phenobarbital treated animals, 7-pentoxyresorufin O-depentylation (catalyzed primarily by P450 2Bx, an orthologue of rabbit P450 2B4/rat 2B1) was inhibited more than 7 ethoxyresorufin O-deethylation (P450 1A1), 4-aminobiphenyl N-hydroxylation (P450 1A2), erythromycin N-demethylation (P450 3A), or benzphetamine N-demethylation; in beta-naphthoflavone-treated animals, 4-amino-biphenyl N-hydroxylation activity was preferentially inhibited. In lung, the order of inactivation of monooxygenase activities was 4-aminobiphenyl N-hydroxylation (4Bx, the orthologue of rabbit 4B1) > 7-pentoxyresorufin O-depentylation activity (2Bx) > 7-ethoxyresorufin O deethylation (1A1; for example 72, 53, and 29% inactivation, respectively, in phenobarbital-treated animals at 100 mg/kg). In all three tissues the loss in spectrally assayed P450 content corresponds quite well to the inhibition of monooxygenase activities. Thus, these studies show that 1-aminobenzotriazole is an effective inactivator of the pulmonary, hepatic, and renal P450 systems in guinea pigs following i.p. administration, and that P450 1A2 (liver) and P450 4Bx (lung), isozymes efficient for the oxidation of primary aromatic amines, are preferentially inactivated. PMID- 1301240 TI - Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging. AB - The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6-8 months) and aged (28-30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously bearing rat hearts, the negative chronotropic response to acetylcholine (10(-9)-10(-5) M) was up to 4 fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 microM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10(-9)-2.5 x 10(-6) M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10(-9)-10(-5) M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations. (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50-60% lower in the aged atria (83 +/- 21) and ventricles (24 +/- 6) than in adult atria (210 +/- 20) and ventricles (47 +/- 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301241 TI - Erythrocyte ion regulation across inactive muscle during leg exercise. AB - Ion concentration changes in whole blood, plasma, and erythrocytes across inactive muscle were examined in eight healthy males performing four 30-s bouts of maximal isokinetic cycling with 4 min rest between each bout. Blood was sampled from the arm brachial artery and deep antecubital vein during the intermittent exercise period and for 90 min of recovery. Arterial and venous erythrocyte lactate concentration ([Lac-]) increased from 0.3 +/- 0.1 to 12.5 +/- 1.3 (p < 0.01) and 1.1 +/- 0.4 to 8.5 +/- 1.5 mmol/L (p < 0.01), respectively, returning to control values during recovery. Arterial and venous plasma [Lac-] increased from 1.5 +/- 0.2 to 27.7 +/- 1.8 and from 1.3 +/- 0.4 to 25.7 +/- 3.5 mmol/L, respectively, and was greater than erythrocyte [Lac-] throughout exercise and recovery. Arterial and venous [K+] increased in erythrocytes from 119.5 +/- 5.1 to 125.4 +/- 4.6 (p < 0.01) and from 113.6 +/- 1.7 to 120.6 +/- 7.1 mmol/L, respectively, decreasing to control during recovery. In arterial and venous plasma, [K+] increased from 4.3 +/- 0.1 to 6.1 +/- 0.2 (p < 0.01) and from 4.5 +/ 0.2 to 5.3 +/- 0.2 mmol/L (p < 0.01), respectively, decreasing to control during recovery. The efflux of Lac- out of erythrocytes against an electrochemical concentration gradient suggests the presence of an active transport system. Efflux of K+ from erythrocytes as blood passes across inactive muscle affords an important adaptation to the K+ release from muscle activated in heavy exercise. PMID- 1301242 TI - Effects of exercise on maternal glycogen storage patterns and fetal outcome in mature rats. AB - The purpose of the present study was to examine the effects of exercise on maternal glycogen storage patterns and fetal outcome in mature (approximately 12 months of age) Sprague-Dawley rats. The exercise consisted of treadmill running at 30 m.min-1, on a 10 degree incline, for 60 min, 5 days per week, for 4 weeks prior to pregnancy, which continued until day 19 of gestation. In mature animals, chronic exercise increased (p < 0.05) liver glycogen concentration in both pregnant and nonpregnant rats. In pregnant exercised animals, the glycogen concentration of the maternal liver increased almost twofold (p < 0.05) compared with the sedentary pregnant group. There was no difference in the amount of glycogen stored in the gastrocnemius or soleus muscles in response to training, pregnancy, or chronic maternal exercise in the mature rat. In the pregnant groups, there were fewer (p < 0.05) viable fetuses and more (p < 0.05) resorption sites than in young rats. In addition, exercise during pregnancy in the mature animal decreased (p < 0.05) fetal body weight. These results demonstrate that a conflict may exist between maternal exercise and fetal demands for energy in the mature rat. This conflict seems to favour the maternal system, as evidenced by the enhanced maternal liver glycogen storage and the negative effect on fetal growth. PMID- 1301243 TI - Echocardiographic findings and the increased risk of stroke in nonvalvular atrial fibrillation. AB - We studied whether cardiac abnormalities contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). M-mode and 2D echocardiography were performed in four age- and gender-matched groups: 20 stroke patients with NVAF, 20 patients with NVAF who had not suffered a previous stroke, 20 stroke patients with sinus rhythm, and 40 healthy controls. Their mean age was 77 years. The two groups with atrial fibrillation differed from healthy controls in that they had more 2D-echocardiographic findings of severe left-ventricular wall-motion abnormalities (p < 0.05) and tended more often to have enlarged left ventricles, and hypertrophic and congestive cardiomyopathy. Left atrial diameter was 47 mm compared to 41 and 39 mm in the two groups with sinus rhythm (p < 0.001). Intracardiac thrombi were only found in the two atrial-fibrillation groups (with stroke: 15% without stroke: 5%). Aortic sclerosis was common in all groups (30-60%), as was mitral annulus calcification (10-20%). The only significant difference between the two atrial-fibrillation groups was a higher frequency of earlier ischemic heart disease in the stroke group. Both atrial fibrillation groups had cardiac abnormalities predisposing for embolic as well as thrombotic stroke. PMID- 1301245 TI - Fasting insulin and left ventricular mass in hypertensives and normotensive controls. AB - The mechanism by which increased left ventricular (LV) mass leads to increased coronary heart disease morbidity and mortality is unknown. We evaluated the relation between fasting insulin and echocardiographic LV mass in hypertensives off medication and normotensive controls, controlling the analyses for blood pressure (BP) and body mass index (BMI). Fasting insulin (p = 0.0217) was the most significant predictor of LV mass in hypertensives, while BMI (p = 0.0265) and diastolic BP (p = 0.0159) were the only significant predictors of LV mass in controls. The relation between fasting insulin and LV mass was not confounded by obesity in hypertensives, but obesity and fasting insulin may interact to predict LV mass. PMID- 1301244 TI - Left ventricular filling dynamics by Doppler echocardiography in dilated cardiomyopathy: one-year follow-up in patients treated with captopril compared to placebo. AB - The role of impaired diastolic function in determining the pathophysiology of congestive cardiomyopathy was only recently appreciated. In the present study, echocardiography and Doppler cardiography were used to determine changes in cardiac size and transmitral filling dynamics over a 1-year period in patients with congestive cardiomyopathy and determine the effect of captopril on these changes. The study population consisted of 27 patients with congestive heart failure in spite of therapy with digitalis and diuretics (NYHA class 3.2). Fifteen patients were started on placebo and 12 on captopril. Noninvasive evaluation was performed at 6-month intervals. Left ventricular size and left ventricular ejection fraction did not change significantly in either group. Forward stroke volume improved significantly only in patients on captopril compared to placebo (p < 0.05). No significant changes in transmitral flow dynamics were observed in the placebo group whereas the captopril-treated group showed a decrease in the peak velocity, flow velocity integral and rate of rapid filling wave (E) and an increase in the peak, integral and rate of filling during atrial contraction (A). The E/A ratio did not change significantly over time in the placebo group, whereas a reduction in the ratio was noted in the captopril treated patients. These changes are sustained over 1 year with concomitant improvement in stroke volume, exercise duration and functional class. PMID- 1301246 TI - Mechanisms involved in cardiac enlargement and congestive heart failure development after acute myocardial infarction. AB - For 3 months, we followed up 40 patients with acute myocardial infarction, 20 were randomly assigned to treatment with captopril and 20 to placebo, to elucidate mechanisms inducing left ventricular volume enlargement and development of congestive heart failure. Echocardiographic follow-up could be obtained in 28 patients, 11 of whom showed more than a 10% increase in left ventricular systolic and/or diastolic volumes (captopril n = 3/15, placebo n = 8/13, p = 0.05). Volume increase was significantly associated with an impairment in exercise capacity (VO2 max in patients with vs. without volume enlargement 24.7 +/- 1.7 vs. 29.5 +/ 1.9 ml O2/kg/min; p < 0.05). Plasma renin activity, angiotensin II and catecholamines were normal in the acute and chronic postinfarction phase in patients on placebo as well as in patients 12-24 h after captopril intake. Plasma atrial natriuretic peptide concentration (ANP) was increased immediately after myocardial infarction, but ANP levels almost normalized in patients with captopril treatment, while they continued to be elevated in patients on placebo. The only technical parameter able to predict left ventricular volume increases was the sphericity index (28.7 vs. 35.7; p = 0.07). We concluded that morphologic deformation and filling pressures as estimated from elevated ANP levels are major factors promoting remodelling following myocardial infarction. ACE inhibitors might exert their favorable effect predominantly by reducing filling pressure. PMID- 1301247 TI - Biphasic changes (initial increase and late decrease) in coronary sinus venous oxygen saturation during anginal attacks induced by intracoronary acetylcholine in patients with variant angina. AB - In order to evaluate the effects of intracoronary acetylcholine on coronary resistance vessels, oxygen saturation in coronary sinus blood was continuously measured to compare its dynamic changes during intracoronary injection of acetylcholine in both patients with variant angina and control subjects. Group 1 consisted of 6 patients without coronary artery disease. Group 2 consisted of 10 patients with variant angina and spasm in the left anterior descending coronary artery. A fiberoptic reflection oximetry system was used for the continuous measurement of coronary sinus venous oxygen saturation. Acetylcholine (20 micrograms) was injected directly into the left coronary artery over 30 s. In the group 1 patients, coronary sinus venous oxygen saturation was increased from 39 +/- 2% (mean +/- SEM) to 54 +/- 3% at 30 s, continuously climbed to 70 +/- 3% at 60 s and then gradually decreased to 53 +/- 5% at 120 s after the initiation of intracoronary injection of acetylcholine. In contrast, in the group 2 patients, coronary sinus venous oxygen saturation was transiently increased from 39 +/- 2% to 56 +/- 4% at 30 s, reversed, decreased to 52 +/- 4% at 60 s and then rapidly decreased to 36 +/- 3% at 120 s with the onset of chest pain associated with electrocardiographic ischemic changes. Coronary arteriography during attacks demonstrated a total or subtotal occlusion of the left anterior descending coronary artery due to severe spasm in all of the 10 patients. The extent of increases in coronary sinus venous oxygen saturation at 30 s after acetylcholine injection was not significantly different between the two groups (group 1: 15 +/- 4%, group 2: 17 +/- 3%). Heart rate, blood pressure and rate-pressure product were essentially unchanged at 30 s after intracoronary injection of acetylcholine in both groups. These data suggest that in control adult humans, coronary blood flow was increased through dilatation of resistance vessels by acetylcholine, while in patients with variant angina, coronary blood flow was transiently increased by dilatation of resistance vessels, after which it was suddenly decreased by spasm of an epicardial artery induced by this agent. Relaxant responses to acetylcholine of coronary resistance vessels appear to be preserved well in patients with variant angina. PMID- 1301248 TI - Cardiovascular effects of cigarette smoking. AB - The risk of cardiovascular morbidity and mortality is greatly affected by cigarette smoking. In order to study the pressor response to smoking, 10 normotensive and 10 mild or moderate essential-hypertensive smokers (> 20 cigarettes daily) were compared with 2 comparable groups of non-smokers. All subjects were asked to smoke 4 cigarettes during 1 h; blood pressure (BP) and heart rate (HR) were monitored beat-to-beat by a non-invasive device (Finapres Ohmeda) during the smoking period and during the immediately preceding non smoking hour. Furthermore, all subjects underwent 24-hour ambulatory BP monitoring. In all groups, each cigarette induced a similar and statistically significant increase from baseline for both BP and HR. The recovery from the marked rise in BP and HR was very slow so that in the smoking hours BP and HR were persistently higher than in non-smoking hours; there were no statistically significant differences between the four groups. During 24-hour ambulatory monitoring both normo- and hypertensive smokers showed higher BP values and higher BP variability in comparison with the respective non-smokers' group. In conclusion, smoking habits were associated with a persistent increase in BP in each group we studied, possibly contributing to a smoking-related cardiovascular risk. PMID- 1301249 TI - Reproducibility of measurements of coronary narrowings by videodensitometry and by digital calipers. AB - Computer-assisted videodensitometry has been shown to be a reliable and reproducible method of measuring absolute and relative coronary narrowings. Using a commercially available analyzer (Vanguard XR70) we confirmed intra- and interobserver reproducibilities in 34 narrowings in 9 patients. Analyses were performed on normal area and diameter, stenotic area and diameter, percent area stenosis and percent diameter stenosis. For all 6 analyses, excellent intra- and interobserver correlations were found (r = 0.93-0.98), with slopes close to 1 and intercepts close to zero. Caliper measurements (Mitutoyo Digimatic) of the same lesions by the same observers showed good inter- and intraobserver reproducibility for percent diameter stenosis (r = 0.90 and 0.86), with mean interobserver difference of 1.67 +/- (SD) 6.4% and intraobserver difference of 2.97 +/- (SD) 7.9%. However, less good correlations were found between caliper and videodensitometric measurements of percent diameter stenosis; r = 0.61 and 0.76 for the two observers. These data suggest that videodensitometry is a highly reproducible quantitative angiographic method, suitable for documenting changes in the severity of coronary artery lesions, both spontaneous or related to interventions. Caliper measurements do not provide the same degree of accuracy, but they have acceptable reproducibility in measuring diameter stenosis. As such, they are also suitable for assessing changes in severity of coronary artery lesions in individual patients. PMID- 1301250 TI - Percutaneous transluminal coronary angioplasty in unstable and stable angina pectoris: a comparison of immediate success and complications. AB - To determine the success rate and the safety of percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris (group 1) versus stable angina (group 2), we studied 299 consecutive patients who underwent coronary angioplasty of 373 consecutive lesions. Of these patients, 149 had unstable angina pectoris and dilation of 188 arteries. The success rate was high and similar in both groups (95 and 93%, respectively). The groups did not differ in regard to the lesion characteristics, vessels and number of sites dilated except for an increase in the presence of thrombus in the unstable angina group (p < 0.03). Although there was a higher incidence of coronary thrombus and more acute myocardial infarction in group 1, the major complication rate did not differ from that of group 2 and was low in both of them (3 and 2%, respectively). No deaths occurred. Six patients (3 in each group) needed urgent coronary artery bypass grafting while 3 additional patients developed acute Q-wave myocardial infarction (all of them in group 1). Thus, percutaneous transluminal coronary angioplasty is a safe and successful procedure in patients with unstable angina as well as in patients with stable angina pectoris. PMID- 1301251 TI - Color Doppler mapping of aortic regurgitation in aortic stenosis: comparison with angiography. AB - Color flow Doppler mapping has become the principal noninvasive method used for the qualitative grading of aortic regurgitation (AR). However, the performance of the color Doppler method in patients with AR accompanying aortic stenosis (AS) has not been studied. We therefore compared results of color Doppler and semiquantitative angiographic grading of AR in 32 patients with AS (mean valve area = 0.7 cm2) undergoing supravalvular aortography in the course of cardiac catheterization. Color Doppler demonstrated AR in all 27 patients who had AR by aortography. As expected, neither the maximal jet area nor the jet length discriminated patients by angiographic grade. The best correlation between color Doppler and aortography occurred when the ratio of maximal jet height (JH) to left ventricular outflow tract (LVOT) height was used to grade AR on a scale of 0 4. Four of 5 patients without AR by aortography had either absent or grade 1 AR by color Doppler. Although there was considerable overlap of color Doppler grades in patients with 1+ AR by aortography, grade 3 or 4 AR by color Doppler was always associated with III+ or IV+ AR by aortography. Thus, color Doppler sensitively depicts AR in patients with AS, and the ratio of JH to LVOT height by color Doppler correctly identifies patients with III+ or IV+ AR by aortography. Methods for distinguishing among milder grades require further evaluation. PMID- 1301252 TI - Extensive calcification in infarcted myocardium: diagnostic value of ultrafast computed tomography. PMID- 1301253 TI - Single coronary artery: a report of 2 cases. AB - An isolated single coronary artery is a rare congenital anomaly. We report 2 patients each of whom had a single coronary artery with an obstructive atherosclerotic lesion in one of its branches. In the first patient angioplasty was successfully performed using a perfusion catheter whilst in the second, the procedure was considered inappropriate as the patient had chronic total occlusion. PMID- 1301254 TI - Regulatory mechanisms of myocardial hypertrophy and fibrosis: results of in vivo studies. AB - Left ventricular hypertrophy is a major risk factor associated with the appearance of adverse cardiovascular events. A distortion in myocardial structure, mediated by an abnormal accumulation of fibrillar collagen within the adventitia of intramyocardial coronary arteries and neighbouring interstitial spaces, alters the electrical and mechanical behaviour of the myocardium. The mechanisms responsible for the regulation of cardiac myocyte growth and collagen accumulation are therefore of considerable interest. Herein we review results of in vivo studies conducted in the authors' laboratory that addressed these issues in various experimental models. The findings indicate that in arterial hypertension myocardial hypertrophy is related to ventricular systolic pressure work. Myocardial fibrosis, on the other hand, is not related to haemodynamic workload, but rather the presence of mineralocorticoid excess relative to sodium intake and excretion. Accordingly, fibrosis can appear in both the hypertensive left and non-hypertensive right ventricles. Pharmacological probes, administered in variable doses, were used to further test and support this hypothesis. In both primary and secondary hyperaldosteronism, it was possible to prevent the pathological structural remodelling of the myocardium with an aldosterone receptor antagonist, while in unilateral renal ischaemia ACE inhibition was similarly cardioprotective. Other studies demonstrated that it was feasible to regress the fibrous tissue response and normalise diastolic stiffness. This concept of cardioreparation suggests that heart failure due to this type of structural remodelling may be reversible. PMID- 1301255 TI - Left ventricular hypertrophy, myocardial blood flow and coronary flow reserve. AB - In this review, the coronary haemodynamics of hypertrophic heart disease are discussed with reference to data published over the last 15 years. Coronary reserve is reduced in the presence of concentric cardiac hypertrophy, but is similar to normal in hypertrophic obstructive cardiomyopathy and aortic stenosis, despite marked left ventricular hypertrophy. A moderate decrease in coronary reserve is found in aortic incompetence and in dilated essential hypertension. In hypertensive heart disease, improvement in coronary reserve can be achieved by long-term vasodilator therapy. PMID- 1301256 TI - Clinical importance of coronary perfusion pressure in the hypertensive patient with left ventricular hypertrophy. AB - In patients with severe left ventricular hypertrophy (LVH), but no significant coronary artery disease (CAD), acute lowering of diastolic blood pressure (DBP) to less than 85 mm Hg is reported to result in a 26% fall in coronary blood flow and an increase in myocardial oxygen demand; S-T segment and T-wave changes in the ECG are observed when DBP is acutely lowered to the 70s in these patients. In the presence of good resting left ventricular function, acute lowering of DBP to the 60s in well-controlled hypertensives on a beta-blocker, with either CAD or LVH, results in a mean increase of about 20% in ventricular ejection fraction. By contrast, patients with a combination of CAD and LVH experience a mean 6% fall in ejection fraction implying poor left ventricular functional reserve. In low risk populations, which exclude patients with severe ischaemia, diabetics and smokers, the lower the DBP the fewer the number of myocardial infarctions. However, in heterogeneous hypertensive populations which include high risk patients, such as ischaemics and diabetics (e.g. the MRFIT population), there is a strong U- or J curve relationship between DBP and CAD deaths. Meta-analysis of high quality studies involving heterogeneous populations has shown that the U- or J-point is at 84 mm Hg and probably relates to high risk patients with ischaemia and/or LVH. Recent data from the Framingham group indicate that the patients most at risk are those with a combination of CAD and LVH: these patients showed a marked U-shaped curve with the U- or J-point at about 85-89 mm Hg DBP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301257 TI - Left ventricular hypertrophy and mortality--results from the Framingham Study. AB - Data on the prognostic implications of left ventricular hypertrophy (LVH) in the Framingham Study based on routine ECG, echocardiogram (ECHO) and X-ray determination with 36 years of follow-up indicate that LVH has emerged as a powerful indicator of rapidly evolving lethal atherosclerotic disease, whether determined by ECG, ECHO or X-ray. Cardiovascular morbidity and mortality increase progressively with left ventricular muscle mass from lowest to highest values. The ECG and X-ray versions of LVH each independently contribute to the risk of cardiovascular events; each adds to the risk associated with the other, and those with both are at greater risk than those with either alone. Risk ratios associated with ECG-LVH are substantial and are greatest for cardiac failure and stroke, but coronary disease is the commonest and most lethal sequela. LVH is reversible, the anatomical variety more so than ECG-LVH, and reversal of this toward normal appears to confer greater benefit for the anatomical rather than the ECG manifestation of LVH. The risk of cardiovascular disease associated with LVH is not uniform, varying widely depending not only on whether there is concomitant ECG and anatomical evidence of hypertrophy but also on the associated hypertension, glucose intolerance, lipid profile and cigarette smoking habit. This suggests that there is much to be gained in correcting those associated risk factors which also promote the development of LVH. PMID- 1301258 TI - Impact of the daily blood pressure load on the development of hypertensive heart disease. AB - Blood pressure (BP) load is a method of data analysis for 24-hour BP recordings that calculates the percentage of elevated pressures above a defined threshold value. This paper reviews the relevance of BP load to indexes of hypertensive target organ disease and the usefulness of the load in assessing antihypertensive therapy. Studies that have assessed the range of BP load and the associations between the load and indexes of hypertensive target organ disease in untreated subjects were included in this review. Additional data from a therapeutic trial have been newly evaluated to assess the effects of lisinopril monotherapy on systolic and diastolic BP load in 30 mild-to-moderately hypertensive patients. BP load, whether taken as a percentage of elevated pressures over the day and night, or as integrated areas under the BP curve, predicts pathological indexes of hypertensive heart disease. In the therapeutic evaluation of BP load, lisinopril reduced systolic BP load from 75 to 44% (p < 0.001) and diastolic BP load from 56 to 29% (p < 0.001). The data have shown a close relationship between BP load and indexes of hypertensive disease. This finding and the ease of use in clinical therapeutic trials suggest that BP load reduction is a worthwhile parameter to follow in studies of antihypertensive drugs. PMID- 1301259 TI - Selection of antihypertensive therapy: cardiac and extracardiac considerations. AB - There are four possible pathophysiological mechanisms which may relate left ventricular hypertrophy (LVH) with cardiovascular morbidity and mortality: LVH diminishes left ventricular filling; LVH decreases coronary reserve and hampers myocardial oxygenation; LVH is commonly associated with ventricular arrhythmias, and with long-standing LVH, left ventricular contractility decreases. LVH can be reduced by a range of antihypertensive drugs, although not all drugs are equipotent in this regard. Two recent meta-analyses have indicated that ACE inhibitors are among the most powerful monotherapeutic modalities to reduce LVH. Calcium channel blockers are almost as effective, whereas beta-blockers and diuretics seem to have a lesser effect, despite equipotent antihypertensive properties. Reducing LVH with ACE inhibitors and calcium channel blockers has been shown to improve contractility and left ventricular filling, and diminish ventricular ectopy. A preliminary study also indicates that coronary reserve increases after reduction in LVH. Despite these promising pathophysiological signs, it remains unknown whether or not a reduction in LVH will reduce morbidity and mortality over and above the reduction achieved by a reduction in arterial pressure alone. PMID- 1301260 TI - [A population-based study on incidence of idiopathic cardiomyopathy in Nanjing, 1985-1989]. AB - The epidemiology of idiopathic cardiomyopathy (ICM) is largely unknown among Chinese population. The purpose of this study was to document the incidence of ICM in the entire residents aged less than 60 years in Nanjing city during the five year period from 1985 to 1989. Using the case registered method it was identified that 275 new cases of ICM collecting from all of the clinically diagnosed outpatients and inpatients in the 14 related hospitals within the city among 2,098,175 residents for years 1985-1989. Over all incidence rate was 2.6 per 100,000 person-years, the age-and sex-adjusted average annual rate being 2.1 per 100,000 directly according to the standardized population of China in 1964 (95% confidence interval 1.9-2.2). This incidence rate was increased from 1.7 per 100,000 in 1985 to 3.3 per 100,000 in 1989 and progressively increasing with aging especially in the groups over 20 years old. Among these 275 patients with ICM, 134 were classified to idiopathic dilated cardiomyopathy (IDCM) and 132 to idiopathic hypertrophic cardiomyopathy (IHCM). Both the average annual incidence rates of IDCM and IHCM were 1.3 per 100,000 and the age-and sex-adjusted rates were 1.1 per 100,000 (95% CI 0.9-1.2) in IDCN and 0.9 per 100,000 (95% CI 0.8 1.0) in IHCM, respectively. The incidence rate of ICM in male was 3.0 significantly higher than 2.2 per 100,000 in female especially in IHCM. The result of this survey is first provided with incidence data of ICM on a broad general population-based study in our country and may be of value in further studying its epidemiology and etiology. PMID- 1301261 TI - [Selection of DSP points in second stage and their presentation]. AB - The principal of selecting DSP points is discussed. Because social and economic development is not balance, developing level of health business and health situation of population are obvious varies in different areas of China. In order to ensure that health information from surveillance population can be used to infer health situation of national population, the feature of geographic, administrative areas and various health situation in different areas are considered. The principals of selecting DSP are: 1. To assure well-balance of geographic distribution of DSP. 2. To assure well-balance of distribution of DSP in different kind of areas, according to above 9 index, GNP, illiterate rate, birth rate, infant death rate, rough death rate, ratio of 0-14 years people to total people, ratio of about 65 years people to total people, ratio of labor in industry to total people, and ratio of labor in agriculture to total people. The way of select DSP is: Multistage stratified random sampling (PPS). Meanwhile in order to avoid systematic error, about 15% points which are no qualified were changed. Therefore whether data from DSP can be represented health level of population of whole nation has been tested. The conclusion is that the data from DSP can indeed do so. PMID- 1301262 TI - [Study on epidemic factors of the decline of cervical cancer mortality in Shandong province]. AB - It is well known that the decline in the incidence or mortality rates of cervical cancer was very significant in the eighties as compared with in the seventies in China. In Shandong province the mortality of cervical cancer was reduced by 76.3 percent during from 1974 year to 1989 year. According to the survival time of patients with cervical cancer in Cangshan county showed that the decline in the mortalities was due to cut down the incidences of it. A birth cohorts study of mortality of the disease was made in the period time of from 1970 to 1989 in Qixia county. The results of which indicated that the cohorts of women who reached puberty after 1949 have much lower rates of cervical cancer than the cohorts of women who reached sexual maturity before that time. The correlation analysis showed the main reason for the decline was related to the elimination of the venereal diseases by the end of 1964 year. The birth control programme having been carried out since the beginning in the sixties also found in relation to the decline of cervical cancer in the eighties. PMID- 1301263 TI - [Seroepidemiological study of hepatitis B virus x antigen (HBxAg) and anti-HBx antibodies in patients with hepatitis B]. AB - A total of 437 patients with hepatitis B were tested for serum HBxAg and anti-HBx in a seroepidemiological study. It was shown that the HBxAg positivity rate was 3.66% (16/437), the anti-HBx positivity rate was 2.97% (13/437). HBxAg was most frequently present in HBsAg, HBeAg, and anti-HBc positive, but anti-HBe negative sera. Anti-HBx was most frequently present in HBeAg and anti-HBc positive, but HBsAg and anti-HBe negative sera. Both the presence of HBxAg and anti-HBx antibodies showed no significant relationship with the presence of serum anti-HBs antibodies. These results indicated that serum HBxAg/anti-HBx system was related to the replications of HBV in the HBV infected human body, and anti-HBx were not protective antibody. PMID- 1301264 TI - [Epidemiological survey of hypertension in the remarried families]. AB - In order to inquire into the relative importance of the genetic and the environmental factors in the hypertension, we made generally survey of 484 remarried families in Tangshan. We made comparison for the prevalence rate of hypertension of the familial members whose blood relationship is not the same. The results of research suggest that the effect of genetic factors is relatively more important than the environmental factors in the familial aggregation of blood pressure. PMID- 1301265 TI - [Report on first finding an epidemic of Scrub typhus in north rural areas]. AB - In the autumn of 1989 and 1990, an epidemic of Scrub typhus occurred in north rural areas in Tianjin. The authors investigated the epidemic on clinical, epidemiological, serological and etiological features, 44 patients were diagnosed serologically or clinically as Scrub typhus and 42 of them (95.5%) were diagnosed serologically by IFA method. 10 sera specimens collected from the patients were determined distinctively by CF method, 8 of them were > or = 1:20 titre to Gilliam type antigen of tsutsugamushi. The try for isolating pathogens failed of success. The epidemic areas is situated in 39.45'-40.05' north latitudes and showed it was the new epidemic area in the north of China. PMID- 1301266 TI - [Study on the infections of U. urealyticum, M. hominis, and C. trachomatis in patients with venereal diseases and healthy controls in three areas of China]. AB - Two hundred and thiry-nine patients with venereal diseases and 264 healthy controls, from Yichang, Liuzhou, and Beijing, were detected for the antibodies to Ureaplasma urealyticum (Uu). Mycoplasma hominis (Mh), and Chlamydia trachomatis (Ct) by indirect hemagglutination (IHA) in 1990. The results showed that: 1) in patients with venereal diseases, the positive rates was the highest in Ct (27.62%), higher in Uu (17.57%), and lower in Mh (4.18%); 2) the levels of antibody to Ct and Uu were significantly higher in the patients than in the healthy controls; 3) in the patients, the positive rate of antibody to Ct was the highest in Beijing (55.88%), whereas, the lowest in Yichang (15.28%); the prevalence rate of antibody to Uu was the highest in Liuzhou (26.23%), whereas, the lowest in Beijing (5.88%); the level of antibody to Mh was not significantly different in the areas mentioned; and 4) the patients with venereal diseases were commonly complicated with infections caused by Ct, Uu, and Mh, there was a new problem to control and treat venereal diseases. PMID- 1301267 TI - [Prospective epidemiological study on the efficacy and safety of female tubal sterilization by chemical instillation]. AB - This is a prospective study on clinical efficacy and safety of female sterilization by chemical agents. A total number of 1705 subjects were randomly divided into two groups. Phenol mucilage (PM) was used in group 1 (834 cases) and phenol-atabrine paste (PAP) was used in group 2 (871 cases). All the characteristics of the subjects were proportionate and comparable to two groups. The follow-up rate was 98.5% at the end of 2 years. Using life table analysis, the results show that the cumulative success rate per 100 women of two groups using PAP and PM was 97.4% and 91.1% respectively. There was significant difference between the two groups. The efficacy of the methods was related with the developed length of roentgenographic shadow after instillation. Multiple discriminatory analysis showed the same results as above. There was no severe complication in all cases. The post-instillation fever rate was 8% in group PAP and 4.4% in group PM, respectively. Our results indicate that female sterilization with the use of chemical agents mentioned is a simple, safe and reliable method in preventing pregnancy. PMID- 1301269 TI - [Self care in the prevention of diarrhea]. PMID- 1301268 TI - [Investigation of rodents and Ixodes for Lyme disease and four strains of Borrelia burgdorferi first isolated from Ixodes granulatus Supino, Rattus confucianus and R. norvegicus in Fujian province]. AB - With BSK II medium, 4 strains of Borrelia burgdorferi was isolated from Ixodes granulatus Supino, Rattus confucianus and R, novregicus, which Ixodes and Ruttus all captured from forest areas in northern of Fujian province where have found Lyme cases. These isolated strains were identified by Institute of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine. PMID- 1301270 TI - [Traditional Chinese herbal disinfectant on air disinfection]. PMID- 1301272 TI - [Elemental diet for preoperative care in colon surgery]. PMID- 1301271 TI - [Nursing care of tubercular meningitis complicated with intracranial hypertension treated with cerebrospinal fluid drainage]. PMID- 1301273 TI - [Nursing care of percutaneous lumbar discectomy]. PMID- 1301274 TI - [Psychological care of patients with cerebrovascular disorders]. PMID- 1301275 TI - [Preventive protection in the dental clinics when treating patients with acquired immunodeficiency syndrome]. PMID- 1301276 TI - [Five essential elements for nursing quality control]. PMID- 1301277 TI - [Follow-up study of 106 cases with permanent pacemaker]. PMID- 1301278 TI - [Postoperative care of microflap transplantation of fingers]. PMID- 1301279 TI - [Nursing care and prevention of transmission of human rotavirus in pregnancy and neonates]. PMID- 1301280 TI - [Nursing care of epidermolysis bullosa drug eruption]. PMID- 1301281 TI - [Nursing care of during clipping intracranial aneurysms microsurgery]. PMID- 1301282 TI - Left or right, up or down: a case for positioning of unconscious head-injured patients. AB - Nursing care activities have been proved to cause increases in intracranial pressure (ICP) which could be detrimental to the patient's health. Because positioning is one of the activities that causes the greatest pressure changes it was evaluated in this study. Cumulative increases also occur when nursing care activities are carried out in quick succession. The analysis of the data and literature suggest that the backrest position with the head of the bed elevated 30 to 45 degrees is the best position for a patient with increased ICP. If further research should prove that this position has a negative influence on the cerebral perfusion pressure, these recommendations will have to be revised. PMID- 1301283 TI - Contemplating a challenging future: a public management approach to health services. AB - A varying proportion of health services in all societies is delivered by public sector institutions. Managing these public sector service institutions for performance represents a major management challenge. This management challenge is amplified for South Africa as a country which is contemplating major changes while being simultaneously confronted with having to cope with problematic results of the past and the challenges of development. In this article a public management model is used to analyse relevant health trends and provisional management strategies are provided to assist health managers to cope with these challenges. Finally a checklist for personal survival is presented for personal evaluation and future planning. PMID- 1301284 TI - [Psychosocial, economic, sexual and religious related needs and problems of women with carcinoma of the breast]. AB - The psychosocial, economic, sexual and religious related needs and problems of women with carcinoma of the breast are explored. White women with carcinoma of the breast experience particular needs and problems related to psychosocial, economic, sexual and religious matters. These needs and problems are also influenced by a number of aetiological factors. Apart from the tension caused by a diagnosis of carcinoma, and particularly one of carcinoma of the breast, the treatment which these women receive contributes to their needs and problems. The research clearly showed that the majority of women did not experience serious problems in coping with their illness--there was a universally low average intensity of needs and problems. They did, however, require help and support in coping with and accepting the consequences of the carcinoma and the attendant treatment. PMID- 1301285 TI - An investigation into the knowledge mothers have about children's growth charts. AB - 218 Mothers who attended the Well Baby Clinic were interviewed to assess their understanding and interpretation of the growth chart. Results were disappointing and recommendations are made. PMID- 1301286 TI - [The status of clinical evaluation at South African universities]. AB - The fact that clinical evaluation is a difficult and complex task of nursing education has been emphasized in the nursing literature since the early seventies. It is, nevertheless, a most important component of the teaching learning process of nursing students and it has definite advantages. It: contributes to the improvement of the standard of nursing care; helps to identify problem areas for research; and contributes to high level professional preparation. In the light of these factors the aims of the study were to: determine and describe the position of clinical evaluation as a component of the teaching of undergraduate students in departments of nursing at universities in Southern Africa; draw up a proto-theoretical model for clinical evaluation. The second aim will be fully discussed in a follow-up article. The empirical data showed that nursing educationists in Southern Africa are not entirely up to standard regarding the skills required for clinical evaluation. PMID- 1301287 TI - Disease-related needs of black patients with cervical cancer. AB - The high incidence of cervical cancer amongst South African black women is complicated by late presentation for treatment as well as by misconceptions and ignorance which adversely affect the quality of their lives. The aim of the research was to determine the disease-related needs of patients suffering from cervical cancer which would serve as a basis for planning on providing for these needs. Needs for the following were identified: Education on early detection in the community. Education on nutrition and hygiene. Information on and assistance in obtaining financial relief by means of subsidized transport and disability pensions. PMID- 1301288 TI - An exploratory study of the ways in which mothers keep their infants occupied. AB - The mother child relationship can help or hinder the social, emotional and intellectual development of the infant. Research has shown that the interaction between mother and child can affect the child's cognitive development. Research has shown that mothers from the lower socio-economic groups do not stimulate their babies optimally and that this may affect the children negatively. In this study 86 underprivileged mothers from two different cultural backgrounds were asked to describe the ways in which they kept their infants occupied during the first year of their infants' lives. The differences between the two groups are discussed and recommendations are made. PMID- 1301289 TI - Preventive self-care in three free state communities. PMID- 1301290 TI - [The contribution of unit managers in the education of student nurses]. AB - The contribution of a group of unit managers towards student education, as well as the problems related thereto, has been investigated contextually by means of an explorative descriptive study, utilising structured interviews. The results indicate that, although unit managers have a positive attitude towards student education, they lack insight regarding the programme content, as well as their own informal educational function in the clinical situation. Lack of time and inadequate liaison between the college and unit managers seem to aggravate this problem. The recommendations include the design and implementation of inservice programmes for unit managers, improved liaison between educational and unit staff, as well as role clarification concerning their informal education responsibilities. PMID- 1301291 TI - [Health education in pregnant women]. AB - Health education and information in pregnancy must be a priority, despite the lack of instruments to evaluate the effectiveness of the education and the fact that positive results can not be guaranteed. During research done for a Masters degree on the utilization of antenatal services by high risk primigravidae at the Tygerberg hospital, patients were interviewed on various aspects that are important during pregnancy, like family planning, breastfeeding, smoking and danger signs that may occur during pregnancy. It was found that education on smoking and alcohol had little impact. However, more patients felt positive about breastfeeding and family planning after they received information about it. A disturbing finding was that patients had very little knowledge about the danger signs that may occur during pregnancy. They did not know the reasons for the examinations and tests performed during pregnancy, although it probably had no negative effect on the attendance of the antenatal clinics. Most of the patients preferred a doctor rather than a nurse to give education and information. It is recommended that health education be looked at critically to ensure that it satisfies the needs of the patients and that the patients' pre-existing knowledge and their educational abilities are taken into consideration. Essential knowledge like the danger signs must be repeated at every visit and the patient's comprehension of it, must be evaluated. It is further not only important to extend the knowledge of nurses on health education, but also to evaluate their competence in giving health education. PMID- 1301292 TI - The science of nursing: current issues and dilemmas. AB - The question regarding the nature and direction of nursing science, how it is derived or why and whether nursing is a science is a much debated one. This article focuses on an examination of the literature with regard to conceptualizations of science in general and nursing in particular with special emphasis on the nature, purpose, methods and domain of science and nursing science. It looks at the various positions taken, examines the consequences of holding any special position and makes suggestions for achieving excellence in Nursing Science. PMID- 1301293 TI - [A facilitation skills program for nursing instructors]. AB - The aim of this study is to discuss the role of the nursing teacher as facilitator of psychological growth in the student, with reference to personality characteristics and skills. A facilitation skills programme is applied to a group of nursing teachers and evaluated by means of a pre, post and post-post psychometric evaluation on an experimental and a control group. Significant positive behavioural change manifested in flexibility in the application of values, feeling sensitivity, internal locus of control and the interpersonal skills of respect, empathy, realness and concreteness. It is recommended that the facilitating role be extended as communication dimension in practical nursing. PMID- 1301294 TI - The problem-solving process with special application to the clinical setting. PMID- 1301295 TI - [The teaching function of the registered nurse--I]. AB - A descriptive exploratory survey was undertaken by means of a questionnaire submitted to student nurses and registered nurses of hospitals affiliated with a nursing college in the Transvaal. The aim of the study was to establish whether, and to what extent, the training function of the ward sister is realised in practice. Analysis of the data showed the ward sister to be aware of her training function and her responsibility towards the student nurse as learner. It appears that the ward sister believes herself to be adequately involved with the basic care of patients and making a significant contribution to the training of student nurses. However, the observations and the experience of the student nurse differ from this point of view. She is of the opinion that more can be done in the ward to help her achieve her training needs. The fact that in many cases she is primarily considered as a worker, comes as a great disappointment. PMID- 1301296 TI - Selection of student nurses at Bafokeng Nursing College. AB - Bafokeng Nursing College is a privately owned institution situated at the Impala Mines in Bophuthatswana. It selects and trains student nurses from all parts of Southern Africa in the comprehensive four-year course who at qualifying are free to work for Genmin or anywhere else in the country. The College is affiliated to Medunsa in offering the four-year comprehensive course. Selection is limited because of limited facilities. The old selection process was evaluated in 1985 and the new selection process started functioning in 1986 when the new course was offered for the first time at the College. With the new selection process, the drop-out rate is very low, the pass rate has improved and the quality of nursing care is improving. PMID- 1301297 TI - Primary mental health care: indications and obstacles. AB - This paper considers indications and obstacles for the development of primary mental health care practice in both developed and under-developed countries. Both are considered as this represents the South African reality. While a significant body of literature has documented the need for primary mental health care, the obstacles (especially in terms of the co-modification of health) to its fruition are seldom addressed. PMID- 1301298 TI - [Computer-assisted instruction in nursing]. AB - According to Kotze (1987:5) the numbers of student nurses showed a constant drop of 10% from 1981 until 1986. It appears that the ratio between the registered nurse and the population will severely worsen. It is therefore necessary that the educational standard of students nurses must be as high as possible to render a comprehensive service to a growing population. Computer-aided instruction can also play a role in the training of student nurses but can also help to keep student nurses as well as registered nurses in touch with the latest developments and introduce them to advanced technology like the computer. PMID- 1301299 TI - [The teaching function of the registered nurse--II]. PMID- 1301300 TI - The phenomenon of caring by the midwife. AB - The child-bearing events are normal physiological processes in the body of the woman and embryo-foetus/baby. Many changes in the internal and external environments of the family take place, simultaneously with these normal processes. These changes lead to the development of certain tasks and responsibilities that must be successfully accomplished by the family during the child-bearing events. Many changes have also taken place in midwifery during the last half of this century. These changes in midwifery practice, together with the changes that take place during child-bearing events, may cause the new family to feel insecure during this stage of their lives. Very often when the family comes into contact with the midwife the factors contributing to feelings of insecurity are present already or soon become present. Their insecurity causes the family to look to the midwife for help and support. The questions that arise are: What are the caring activities which the midwife should carry out to assist and facilitate the new family to grow on the health continuum during the postnatal period? How can the humanistic values of caring be combined with the scientific knowledge base that guides the midwife's actions to form the science of caring? A description of the midwife's caring functions during the post-natal period, in the hospital as well as in the community, is therefore essential. Thereafter, formulation of valid standards for postnatal care by the midwife can contribute to quality post-natal care in South Africa. PMID- 1301302 TI - The postnatal review: the task of the midwife. AB - There is growing realization that women's health and involvement in health care are essential keys to health for all. One way in which the midwifery profession can contribute to women's health is by providing high quality care during the six week postnatal review/checkup. A study in three provincial hospitals in the Port Elizabeth area showed that the actual structure of the postnatal review fell far short of the ideal as specified by the literature. Of all the elements included in the ideal postnatal review, only 23.5% of these were performed or supervised by the midwife. Seventy percent (70%) of these elements were not performed at all, thus emphasising the fact that a comprehensive health service is not being provided at the postnatal clinics in Port Elizabeth. PMID- 1301301 TI - [Communication with patients--the effect of verbal and nonverbal communication on the unconscious patient]. AB - Communication, both verbal and non-verbal, is a greatly neglected skill at present. Two reasons given for this state of affairs are lack of time and lack of interest in others. Since it is difficult to separate verbal and non-verbal communication, the effects of both types were studied, whether or not they occurred simultaneously. Empirical evidence shows that unconscious patients are highly sensitive to the nature of communication, and that their intracranial pressures rise or fall concomitant in the way in which a conversation is being conducted within hearing distance. Music and touch seem to have similar consequences. The influence of communication is, however, not confined to intracranial pressure changes. The sympathetic and parasympathetic nervous systems are also affected, with associating changes in the heart rate. Messages of acceptance or rejection may be conveyed verbally or non-verbally. Communication with patients appears to be decisive, and should therefore warrant far greater attention than it receives at present. PMID- 1301303 TI - Management of intravenous therapy in general wards of a large teaching hospital. AB - The monitoring of intravenous therapy by nursing staff in medical wards over an 18 hour period was studied. The study focused on the measuring or flow rates, the technique used for unblocking intravenous lines and how recording was managed. Only intravenous therapy which was likely to be in situ for longer than a 24 hour period was studied in randomly selected medical wards. Procedures were carried out by all categories of staff. Although timing devices were used for flow rates they were still incorrect. A need for improved recording was established and no clearly defined methods for unblocking intravenous lines were found. PMID- 1301304 TI - [Psychiatric patients experiences of their treatment by the interprofessional health team in a private psychiatric hospital]. PMID- 1301306 TI - Developing critical thinking skills. PMID- 1301305 TI - The unbooked maternity patient in an academic hospital in Durban. AB - This paper examines the unbooked maternity patient in an academic hospital in Durban, Natal. This hospital is the biggest hospital serving the underprivileged population of this area. Of the 16,000 annual deliveries in this hospital, about 12% are unbooked patients. The health belief model of Rosenstock, as interpreted by Mikhail, and Cox's interaction model of client health behaviour were used as a theoretical framework for this research. A qualitative case study methodology was undertaken and semi-structured interviews were conducted with unbooked mothers who had utilized appropriate health services in a previous pregnancy. The aim of such interviews was to explore reasons given by mothers for non-use of facilities in the current pregnancy. The basic trends reflected in the findings regarding non-utilization of health services were client instability, health service failure and socio-cultural constraints. The study is innovative and addresses the problem from a social-cultural and midwifery perspective. PMID- 1301307 TI - A concept analysis of nurses' commitment to patient care. AB - Commitment to the service of mankind has always been a key concept of professional nursing. However, very little effort seems to have been made to analyse the nature of commitment as a factor in nursing. This article explores the meaning of the concept 'commitment' as revealed by a review of the literature and the responses of a group of registered nurses in unstructured interviews. It goes on to analyse the concept by means of a number of techniques such as an analysis of critical attributes, the construction of model cases and related cases, the identification of antecedents and consequences and of empirical referents. The information gleaned was used to structure a study of the commitment to patient care of a group of professional nurses which will be published in a subsequent article. PMID- 1301308 TI - The standards for postnatal care by the midwife in the hospital and the community. AB - The child-bearing events are normal physiological processes in the body of the woman and embryo/foetus/baby. Many changes in the internal and external environments of the family take place, simultaneously with these normal processes. These changes lead to the development of certain tasks and responsibilities that must be successfully accomplished during the postnatal period. A description of the midwife's caring functions during the post-natal period, in the hospital as well as in the community, is therefore essential. This description forms the part of an article that was published in the previous issue of Curationis. Thereafter the formulation of valid standards for postnatal care by the midwife can contribute to quality post-natal care in South Africa. The aim of this second part of the study was to formulate valid general standards for postnatal care by the midwife; Concept standards were formulated with the model of postnatal care and the stated prerequisites of caring as conceptual framework. The statistical validity of all the standards were determined by midwifery experts. PMID- 1301309 TI - [Knowledge and expectations of childbirth in primigravidas]. AB - The primigravida's experience of childbirth is influenced by the knowledge and expectations she has of childbirth. Her expectations of childbirth are based on the information she got from the antenatal clinic, the nursing staff, her mother, friends and family. The purpose of this research was to determine the knowledge and expectations the primigravida has of childbirth. An exploratory, descriptive design was used within the context of an academic hospital in Johanneburg. The survey method was used. The method of research firstly consisted of a literature study of the primigravida's knowledge and expectations of childbirth. This was done in order to put the problem in perspective and also to serve as a theoretical framework for the study. Secondly, a structured questionnaire was used to make a survey of the primigravida's knowledge and expectations of childbirth. From this research it is clear that the respondents had insufficient knowledge of childbirth and the handling of pain during childbirth. This insufficient knowledge can mainly be attributed to the poor attendance of antenatal preparation classes, inadequate professional counselling and the mother of the primigravida as the primary source of information on childbirth. The respondents, however, had realistic expectations with regard to their handling of labour, as well as of the role of the midwife and the doctor. From this research it is clear that a large gap exists in the primigravida's preparation for childbirth. The group participating in this research is therefore not adequately prepared for childbirth to have realistic expectations. The group must rely on the support of the midwife in the labour ward.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301310 TI - A model for clinical evaluation. AB - After grappling for years with the problems associated with clinical evaluation in nursing, and becoming increasingly aware of the importance of this aspect of the clinical teaching process, the researcher resolved to make an in-depth study of the state of clinical evaluation in nursing. The study was undertaken in the second semester of 1990. The most important findings of this research were discussed in a previous article (Mulder, M. and Viljoen, JJ. 1992. Die stand van kliniese evaluering aan Suider-Afrikaanse Universiteite. CURATIONIS, Vol. 15, No. 1, 29-41). The second aim of the study, i.e. the development of a proto theoretical model for clinical evaluation, is discussed in this article. Since there was no existing model for Southern Africa which reflected the researcher's philosophy and view of clinical evaluation, she constructed one as an implicit part of the main recommendations of the research. This model is presented as the ideal for clinical evaluation. The model can be used by evaluators and researchers to assess, plan, implement, remedy and to solve problems of clinical evaluation. It can also be used to direct future research. PMID- 1301311 TI - Dilemmas of clinical teaching. PMID- 1301312 TI - An evaluation of late attenders in labour in Alexandra. AB - To study why women present in late labour we interviewed 70 parturients in our labour room for a period of 8 days in March 1990. When presenting 19% were 8-10 cm dilated and 81% were 0-7 cm dilated. The group was stratified into those in early labour (0-7 cm of cervical dilatation) and in late labour (8 cm or more) and compared for all variables studied. Only a few differences were statistically significant. Early comers were less likely to have strong uterine contractions and more likely to have intact membranes at presentation. Late comers were more likely to report a number of delaying factors or to have financial worries. Twenty nine percent of Alexandra residents and only 6% of outsiders reported difficulty in finding transport to labour room after the onset of labour. Almost half of Alexandra residents did not have access to public transport, ambulance or own transport. The relative risk for late coming was: 9 for women reporting a number of delaying factors outside their control; 6 for those with financial worries or with ruptured membranes; 4 for unbooked cases or with current addresses in Alexandra; 3 for women with a normal past obstetric history or with a previous delivery outside the AHC; 2 for those worried with hospital referrals, with a previous rural address, for less than 1 year in Alexandra or with a normal current ANC. Women who came late in labour were more likely to need hospital referral or to have come to the labour unit walking. PMID- 1301313 TI - The status of nursing research in the Republic of South Africa: past and present perspectives. PMID- 1301314 TI - Using hospital archival data to research the history of nursing: King George V Jubilee Hospital--an example. PMID- 1301315 TI - [A model for qualitative research in nursing]. AB - The aim of the research is to describe a model for research in Nursing from the Model of Botes (1989). Within a contextual, qualitative, descriptive design a model for research in Nursing is described through a literature study, script- analysis and intersubjective debate. The method of research went through five phases. The model for research in Nursing is described accordingly the assumptions of the model, a visual presentation, definition of the central concept and statements in the model. The model is evaluated and recommendations for implementation are given. PMID- 1301316 TI - Commitment to patient care: an exploratory study among registered nurses in Bophutatswana. AB - In this second article on the commitment to patient care the methodology and results of the study are briefly described and discussed. The research method was a non-experimental qualitative survey, using several data-gathering methods such as semi-structured interviews with registered nurses and patients, the examination of nurses' and patients' records and non-participant observations. Although the responses of nurses and patients indicated that both groups considered commitment to be essential to patient care, the examination of patient records, nurses' evaluation reports and observations showed lack of commitment in practice. Various reasons for this are explored and recommendations made. PMID- 1301317 TI - [Visual agnosia evolving to optic aphasia--a case study]. AB - The underlying mechanism of visual agnosia and optic aphasia has not been fully elucidated, although a number of hypotheses have been proposed. Besides, the difference between these two conditions has been a matter of debate. We report here the result of neuropsychological evaluation in a case of associative visual agnosia evolving to optic aphasia. A 64-year-old right-handed patient was found to be disoriented and confused after undergoing the operation of gastrectomy. CT scan revealed a large infarction in the territory of left posterior cerebral artery. Since 3 weeks after onset, neuropsychological investigations were carried out during 5 months. He was alert and co-operative. Right homonymous hemianopia with macular sparing was noted, but his visual acuity was normal. There was neither a global deterioration of intellectual capacities nor aphasia. Most striking finding was his difficulty in identifying common objects and colours along with a profound alexia. Prosopagnosia was absent. Visual naming both for objects and line drawings was severely impaired. He was unable to describe or demonstrate the use of the objects which could not be named. Pointing to objects named by the examiner was also severely impaired. Although tactile naming was also impaired, both of auditory naming for environmental sounds and naming objects in response to verbal descriptions were preserved. While he was not able to copy the objects skillfully, matching of identical objects and matching objects to line drawings were normal. Clumsiness of coping was thought to be due to his constructional apraxia and visuomotor ataxia. Therefore, his deficit in visual domain was considered to be associative visual agnosia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301318 TI - [Magnetic resonance angiography in 12 patients with Wallenberg's syndrome]. AB - Magnetic resonance angiography (MRA) was performed in 12 patients with Wallenberg's syndrome (WS) in chronic stage to investigate the lesion of the vertebral artery (VA). The laterality of infarction in the medulla oblongata was confirmed with MRI: the right in four patients and the left in eight. In this study, time-of-flight MRA was evaluated. Coronal and OM sections in MRA were examined, because the former is useful to observe asymmetry and curve of the cervical VA, and the latter is useful to observe asymmetry and stenosis of the intracranial VA. In nine out of 12 patients, the ipsilateral VA was rather hypoplastic compared to the contralateral VA, and the flow of the hypoplastic VA stopped before and after entering the intracranial region. The contralateral VA of the hypoplastic cases showed curve in the neck in five patients and stenosis in the intracranial portion in one patient. A comparative study was conducted between vertebral angiogram (VAG) and MRA in four patients. Both VAG and MRA were useful in detecting hypoplasia and stoppage of the flow. It was considered that VA hypoplasia is frequently responsible for WS, and that MRA is useful in screening the vascular lesion as a non-invasive procedure to reveal changes of the bilateral VA. PMID- 1301319 TI - [A clinicopathological study on 13 cases of motor neuron disease with dementia]. AB - Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1301320 TI - [Morphometry of the normal cadaveric cervical spinal cord]. AB - We measured the cross-sectional area and diameters of the C7 segment in 80 cadaveric specimens obtained from patients without spinal cord lesions died at 60 to 79 years of age. We found considerable individual variation in the spinal cord size. The transverse area of the C7 segment varied from 33.3 mm2 to 67.7 mm2 (mean 48.4 +/- 6.9 mm2). The size of the cord had no correlation with body weight, and had some correlation with body height. But the individual variation in the cord size was considerably large even among the cases of the same height. This large variation in the cord size should be under consideration in morphometric analysis of the spinal cord. We showed the morphometric data based on the measurements of the cross-sectional area and diameters in each segment from C2 to Th1 in 14 cases. Although the size of the spinal cord varied markedly from case to case, the relative ratio of cross-sectional area in each segment to that of C3 was similar among the cases (C2; 1.01 +/- 0.04, C4; 1.02 +/- 0.03, C5; 1.09 +/- 0.04, C6; 1.09 +/- 0.06, C7; 1.07 +/- 0.06, C8; 0.98 +/- 0.05. Th1; 0.80 +/- 0.04). Based on our data, the proper cross-sectional area of each segment and of each individual may be calculable from measurement of a given single segment. PMID- 1301321 TI - [Big-toe localizing test--clinical study of proprioceptive localization]. AB - Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space. In the previous study (Hirayama, Fukutake, et al., 1986), we demonstrated that such kind of proprioception, which we called "proprioceptive localization", could be detected by making the patient pick up the thumb with the opposite fingers (the thumb localizing test, TLT). As a further development of the TLT, another test, named a big-toe localizing test (BTLT), was devised. In the BTLT, the patient, with eyes closed and a lower limb passively immobilized by the examiner (the fixed limb), is asked to point to the big toe with the index finger of one hand or the other (the reaching limb). Firstly, we assessed the unselected series of 33 patients with thoracic or lumbar myelopathy regarding their sensory impairment and obtained the following conclusions on the BTLT similar to those in our previous study on the TLT. (1) BTLT deficits results from perceptive impairment in the fixed limb. (2) The perceptual information involved in the proprioceptive localization is different from that of the test for the appreciation of passive movement and posture. (3) On the basis of the correlation to other symptomatology, it is suggested that BTLT deficits arise from lesions of the posterior column-medical lemniscal system. (4) The BTLT is more sensitive than the test for the appreciation of passive movement and posture. Secondly, we evaluated another unselected series of 63 patients with unilateral TLT deficits due to CNS lesions. Eight patterns of BTLT deficits were identified and classified into 3 following types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301322 TI - [Cerebrovascular CO2 reactivity in patients with dementia due to multiple infarction in the territory of the perforating artery]. AB - In order to clarify the pathophysiology of dementia due to multiple infarction in the territory of the perforating artery, the reactivity of cerebral vessels to increased carbon dioxide tension was examined in patients with multiple cerebral infarction with or without dementia. The subjects studied were 11 patients with multi-infarct dementia (MID) (age 57-82 years old, mean +/- S.D. 72 +/- 8) and 16 patients with multiple infarction without dementia (MI) (age 51-81 years old, mean +/- S.D. 69 +/- 9). The diagnosis of cerebral infarction was based on the clinical signs and symptoms and findings of magnetic resonance imaging (MRI). Only patients with cerebral infarction located in the perforator territories were included in this study. Dementia was diagnosed by DSM-IIIR criteria. The extent of periventricular high intensity area (PVH) on the T2-weighted image of MRI was classified into 3 subgroups by the criteria of Gerard et al with some modifications. Cerebral blood flow (CBF) was measured by the 133Xe intravenous injection method using a Cerbrograph (Novo), and gray matter flow (F1) and initial slope index (ISI) were calculated. The cerebrovascular reactivity to CO2 was estimated as the increase in F1 or ISI per unit increase in PaCO2 (delta F1/delta PaCO2 or delta ISI/delta PaCO2, respectively) during inhalation of 5% CO2 and as %increase in F1 or ISI per unit increase in PaCO2 (delta F1%/delta PaCO2 or delta ISI%/delta PaCO2, respectively) during inhalation of 5% CO2. 1. CO2 reactivity in both groups. delta F1/delta PaCO2 in the MI and MID groups were 3.2 +/- 1.4 ml/100 g/min/mmHg and 2.0 +/- 1.4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301323 TI - [Naming difficulties seen in a case of alexia with agraphia caused by a left postero-inferior temporal lesion]. AB - A 71-year-old right-handed man presented writing and reading difficulties as well as naming difficulties. Neuropsychological examinations revealed mild fluent type aphasia accompanied by alexia and agraphia predominantly affecting kanji and also severe naming difficulties. Brain MRI showed cerebral subcortical hemorrhage extending from the anterior one-third of the left temporal lobe to the temporo occipital junction involving the fusiform gyrus. The analysis of the several reported cases with severe alexia with agraphia for kanji including ours revealed a close correlation between the severity of kanji writing disturbances and that of naming difficulties. It was also shown that cases with severe naming difficulties had lesion extending anteriorly to the anterior middle temporal gyrus or medially to the parahippocampal gyrus, suggesting that the disconnection between the parahippocampal gyrus and other cortices including the temporal lobe was essential for production of naming difficulties. PMID- 1301324 TI - [A case of B-cell lymphoma with clinical and histological features of malignant histiocytosis]. AB - A case of B cell lymphoma with clinical and histological features of malignant histiocytosis was described. A 57-year-old male was admitted to Shinshu University Hospital because of transverse myelopathy. Five months before admission, he noticed urinary disturbance, which progressed to urinary obstruction. The following month, bilateral muscular weakness appeared in his legs. A few days later he could not stand up, and was admitted to a local hospital. Neurological examination revealed sensory disturbances below the level of Th12 in all modalities, and marked weakness and hyperreflexia in the lower limbs. A spinal tumor was suspected. However, myelography showed no abnormality. The patient's condition worsened and he became bed-ridden in February 1990. He was transferred to Shinshu University Hospital for further evaluation. On admission he was poorly nourished with fever, anemia, hepatomegaly, and bilateral pretibial pitting edema. No lymphadenopathy was observed. Neurological examination showed total sensory loss below the level of Th12, spastic paraplegia, hyperreflexia in the legs, and urinary obstruction. Laboratory findings revealed an elevated erythrocyte sedimentation rate, increased CRP, pancytopenia, and hypoalbuminemia. Serum level of IgG, IgA, IgM, LDH, ALP, GPT and total bilirubin were increased. CSF and MRI imaging of the spinal cord were normal. Proliferation of atypical histiocytes with marked erythrophagocytosis, which is a characteristic pathological feature of malignant histiocytosis, was observed in peripheral blood and aspirated bone marrow. Immunoenzyme staining of bone marrow using monoclonal antibody L-26, which is a B-cell marker, revealed B cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301325 TI - [An autopsied case of Parkinson's disease manifesting Shy-Drager syndrome]. AB - We report an autopsied case of Parkinson's disease manifesting Shy-Drager syndrome. At the age of 63 years, the patient noticed an onset of progressive orthostatic dizziness, which was followed by constipation, dysuria, and sexual impotence. When he was 66 years old, syncopal attack for a few minutes, tremor in the bilateral hands, and memory disturbance developed. On admission, his blood pressure was 142/72 mmHg in supine position, which fell to 58/42 mmHg on standing with appropriate increase of heart rate. Neurological examination revealed hallucination, memory disturbance, masked face, muscular rigidity, bradykinesia, mild postural tremor, and autonomic dysfunction including severe orthostatic hypotension, hypohydrosis, constipation, dysuria, and sexual impotence. Electroencephalogram showed diffuse slowing. Brain CT demonstrated absence of severe atrophy of the cerebellum, and brain stem. Pharmacological study revealed denervation hypersensitivity to the intravenously administrated noradrenaline. A diagnosis of Shy-Drager syndrome was made, and he was treated with anti parkinsonian drugs. However, no improvement was observed in his clinical symptoms. Seven months later, he died of pneumonia. Neuropathological examination revealed marked neuronal cell loss and gliosis in the substantia nigra and locus ceruleus. Lewy bodies were seen in those pigmented nuclei, dorsal vagal nucleus, hypothalamus and nucleus basalis of Meynert. No abnormality was found in the intermediolateral nucleus of the spinal cord. This is the first report on a Japanese patient who presented clinically Shy-Drager syndrome and pathologically typical Parkinson's disease. In this patient, from the pharmacological and pathological findings, sympathetic ganglia were supposed to be the responsible lesion for orthostatic hypotension. PMID- 1301326 TI - [A case of periodic ataxia]. AB - We report a sporadic case of periodic ataxia characterized by recurrent attacks of vertigo and ataxia. A 62-year-old male was known to have nystagmus at the age of 18. He has had recurrent episodes of vertigo and ataxia since the age of 48. During an attack remarkable downbeat nystagmus, limb ataxia predominant in the lower extremities and ataxic gait were present. MRI demonstrated an atrophy of the anterosuperior region of the cerebellar vermis. Vertical nystagmus, dysesthesia of gloves and stocking type and deep sensory disorder persisted during interictal intervals. There is no finding which supports this case to be vascular disorder, congenital anomaly, tumor, infection or demyelinating disease. We thought this case to be periodic ataxia and to belong to vestibulocerebellar ataxia reported by Farmer and his colleagues. PMID- 1301327 TI - [A case of progressive supranuclear palsy presenting mouth opening difficulty with tonic contraction of the orbicularis oris muscle]. AB - A 72-year-old man developed supranuclear ophthalmoplegia, bradykinesia, rigidity, unsteady gait, dementia, dysphagia, retrocollis, grasp reflex and apraxia of eyelid opening. These findings were compatible with progressive supranuclear palsy (PSP). At the age of 66, he presented a peculiar phenomenon characterized by simultaneous tonic contraction of the orbicularis oris muscle (OOM) and the palatal muscles elicited by pronouncing "pa", which resulted in difficulty of voluntary opening of the mouth and the rhinopharynx. Therefore, the respiration air reciprocated between the lung and the closed mouth. The expiratory pressure puffed out the cheeks, while the lips remained tightly closed. While the respiratory movements and the pressure increased by degree, the OOM contracted more strongly in proportion to the pressure. Sixty to ninety seconds after the elicitation, the pressure overcame the contraction of the OOM and the course of the phenomenon was completed. The electromyograms showed that the OOM activity was prolonged after initial voluntary contraction, remaining thus after a tracheostomy for pneumonia at the age of 72, and that it increased in response to the pressure. Apraxia of eyelid opening, one of the other symptoms, resembled this phenomenon in terms of the aspect of difficulty of voluntary mouth opening. The "holding" phase of grasp reflex, yet another symptom, resembled it in the recruitment of the OOM activity. The phenomenon is not common in patients with PSP. However, we concluded that it may be included among the symptoms of PSP because it has similar characteristics to apraxia of eyelid opening and grasp reflex, which are not uncommon in patients with PSP. PMID- 1301328 TI - [Cerebellar infarction presenting erotic delusion and delusion of jealousy in the acute phase]. AB - A 62-year-old female presented peduncular hallucinosis accompanied with outstanding manifestation of delusion of jealousy and erotic delusion in the acute phase of cerebellar infarction. The delusion seemed to appear as the swollen cerebellum was compressing the tegmentum of brainstem. CT scanning revealed the sequential images of the compression by the swollen cerebellum and deformity of the brainstem and their final recovery. The reason why the patient showed the outstanding delusion that is unusual in the ordinary peduncular hallucinosis is unclear. It might be brought about by the acute hydrocephalus induced by the occlusion of aqueduct. PMID- 1301329 TI - [Multiple system atrophy with macro square wave jerks and pendular nystagmus]. AB - A 51-year-old woman was admitted to our hospital because of gait disturbance and dysuria. Neurological examination revealed limb and truncal ataxia, orthostatic hypotension, cogwheel rigidity in all limbs, generalized hyperreflexia without pathological reflex, and horizontal gaze nystagmus. She became progressively worse and bedridden at age 52. Then she developed abnormal eye movements. Electrooculogram revealed vertical, horizontal or oblique macro square wave jerks and pendular nystagmus. Macro square wave jerks appeared during fixation and disappeared with eye closure or in the dark room. Macro square wave jerks were characterized by a duration of about 200 msec and an amplitude of 10 to 15 degrees. Pendular nystagmus with a duration of several seconds and amplitude of 5 to 15 degrees appeared when she changed her fixation or the point of fixation disappeared. Macro square wave jerks and pendular nystagmus were mildly suppressed after the intramuscular injection of 100 mg of phenobarbital, the oral intake of sodium valproate of 600 mg/day or baclofen of 60 mg/day. They were almost completely depressed after the intravenous injection of 3 mg of diazepam or the oral intake of clonazepam of 1.5 mg/day. We suggested that both macro square wave jerks and pendular nystagmus in this patient might be caused by the dysfunction of GABAergic system in the saccadic eye movement system. PMID- 1301330 TI - [A case of acid maltase deficiency (juvenile type)--immunohistochemical and biochemical study]. AB - A 22-year-old housewife was referred to us for review of progressive proximal muscle weakness which started at 15 years of age. A biopsy of left rectus femoris muscle showed acid phosphatase positive vacuoles partly filled with PAS-positive material. Acid maltase activity of the cultured fibroblasts was pathologically low at 0.4 nmol/mg protein considering 161.0 +/- 32.4 nmol/mg protein as a normal range. A diagnosis was made of acid maltase deficiency (juvenile type). Western blot using anti-acid maltase polyclonal antibody revealed 115 and 70 kDa bands in control muscles, where as only the 115 kDa band, a presumable precursor of the enzyme, was visualized in the patient. By immunohistochemistry using the same antibody the epitope was localized to the acid phosphatase positive vacuoles and immunoelectron microscopy demonstrated the acid maltase immunoreactivity within lysosomes. We concluded that the protein precursor unable to proceed into mature enzyme can access to lysosomes from endoplasmic reticulum through Golgi complex in the present case. PMID- 1301331 TI - [Cervical root avulsion presenting proximal segmental muscular atrophy of unilateral upper extremity]. AB - A 56-year-old woman noticed non-progressive weakness in the proximal part of the right upper extremity from her childhood. At the age of 37 years, she was diagnosed as "spinal muscular atrophy" by an orthopedic surgeon. At the age of 56, neurological examinations revealed muscular atrophy and weakness confined to the right deltoid, biceps brachii and brachioradialis together with minor sensory disturbance in the lateral side of the right shoulder and forearm without pyramidal sign in the lower extremities. The neurological features of this case differed from those of juvenile type of distal and segmental muscular atrophy of upper extremities in distribution of muscular atrophy, and simulated those of cervical spondylotic amyotrophy. Myelography demonstrated root avulsion of the right C5 and C6 roots. CT myelography revealed traumatic meningocele. Therefore a clinical diagnosis of cervical root avulsion resulting from unrecognized birth injury was made. The reason of motor dominant pictures of this case may be vulnerability of the anterior nerve roots to traction injury. PMID- 1301332 TI - [A case of acute multiple sclerosis mimicking tumor on the neuro-imaging studies]. AB - A 31-year-old woman with a history of suspected optic neuritis was admitted with weakness of right-sided extremities and confusion. On admission general physical examination revealed no abnormality. Neurological examination revealed central facial palsy, mild hemiparesis and hemisensory deficit on the right side. Cerebrospinal fluid analysis showed monocytosis of 29 cells, protein of 82 mg/dl, glucose of 62 mg/dl and myelin basic protein of 6.8 ng/ml. No oligoclonal bands were seen. X-ray computed tomographic (CT) scans showed multiple homogeneous contrast-enhancing lesions in the white matter of bilateral parietal lobes without distinct edema or mass effect. Follow-up CT scans showed ring-enhanced lesions. Magnetic resonance image (MRI) showed multiple Gadolinium-enhanced lesions. Additionally, 123I-IMP SPECT [Gamma view-SPCT 2000 H-20 (Hitachi Co.)] was performed at 30 minutes and 5 hours after intravenous administration of IMP (3 mCi). It showed high IMP uptake corresponding to the CT and MRI lesions. Cerebral angiography was considered to be normal. Other laboratory findings were within normal limits. A biopsy was performed. Histological examination showed spongiosis, gliosis and perivascular cuffing. The histological diagnosis was acute demyelinating disease. After therapy with methylprednisolone, she improved gradually. Enhanced lesions in CT and MRI may correspond to active demyelination at acute MS. High uptake of SPECT may also appear in acute stage, although it has not been reported. We should perform neuro-imaging studies including SPECT on acute MS. PMID- 1301333 TI - [A case of cerebral infarction presenting as retrosplenial amnesia]. AB - We report a 73-year-old right-handed female who presented with an acute amnesic syndrome. On November 18, 1991, she was admitted to a local hospital complaining of sudden-onset vertigo and nausea, but immediately after the admission she developed an amnesic syndrome. On November 27, she was transferred to our hospital for further assessment of her memory disturbance. Neurologically she was normal except for mild right hemianopsia and increased deep tendon reflexes in the extremities. Neuropsychological assessments were performed over 3 weeks. She was always alert, attentive, and cooperative. She had no confabulation. On the Wechsler Adult Intelligence Scale revised (WAIS-R), her total IQ was 110. Frontal, verbal, and perceptual functions and motor performance were normal. She had no signs of a callosal disconnection. Despite these preserved functions, her memory function was obviously disturbed. Several memory betteries showed that her recent memory for both verbal and visual modalities was impaired, while her immediate memory such as digit span was preserved. For remote memory her retrograde episodic memory concerning both personal and public events was almost intact, although she had a profound anterograde amnesia. In particular she recalled her personal information about just-premorbid events in detail. On the other hand, her semantic memory, for example understanding of proverbs, geography, and scientific law, was preserved. Taken together, her procedural memory on learning tasks, such as "Tower of Hanoi" and mirror drawing, was intact. Computed tomography demonstrated a low-density area medial to the trigon of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301334 TI - [Serial magnetic resonance imaging of spinal syrinx formation in a case of multiple sclerosis]. AB - A 27-year-old woman had a subacute onset of back pain, dysesthesia and weakness of both arms. Neurological examination revealed bilateral pyramidal signs, paresthesia of both hands and arms, and hypalgesia below T-4. CSF showed no abnormal findings. T2-weighted MR images revealed linear high signal within the cervical and upper thoracic cord, but no syrinx. The signs and symptoms resolved substantially within three months, with the exception of paroxysmal itching localized to the right forearm. At age 30, she experienced an acute onset of back pain, and dysesthesia of both feet. She developed weakness of both legs and urinary retention two days after the onset. Neurological examination showed bilateral pyramidal signs in the lower extremities, hypalgesia below T-4, hypopallesthesia on both legs, but no abnormalities in the upper extremities. CSF contained 8 white cells/mm3, protein 17 mg/dl and glucose 44 mg/dl. Oligoclonal bands were not detected. T1-weighted, proton density, and T2-weighted MR images revealed a syrinx formation within the spinal cord, extending from the level of T 2 to T-5. There was no evidence of spinal tumor. MRI of the brain revealed multiple areas of high signal intensity on T2-weighted image, consistent with multiple sclerosis. The signs and symptoms resolved substantially within two months. The syrinx within the thoracic cord reduced in size after two months and disappeared after three months. Two months after the second episode of myelopathy, she experienced right optic neuritis, resolving substantially within three weeks. This case was diagnosed as definite multiple sclerosis based on the clinical and radiological findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301335 TI - [A case of chronic multifocal myositis]. AB - A 61-year-old civil engineer began to have slowly progressive muscle atrophy in the right shoulder and the left arm at 56 years of age. Muscle wasting became manifest in the left thigh at 59 years and in the right thigh at 60 years. He had mild difficulty in climbing and descending stairs. On examination, although he had notable muscle atrophy in the right trapezius and proximal muscles in the upper and lower extremities, his muscle strength was relatively well preserved. The muscle atrophy was asymmetrical; the right periscapular region and the left upper and lower extremities were more markedly atrophic. In addition, multiple foci of the striking muscle atrophy were noted in the upper trunk and the proximal limb muscles. Fasciculation was not present. Deep tendon reflexes were normal with no pathologic reflexes. Except for a moderately elevated serum creatine kinase level of 709 Ul/l (normal 40-170) and mildly elevated serum myoglobin level of 100 ng/ml (normal < 60), no laboratory tests showed abnormal values suggesting an inflammatory process. Motor and sensory nerve conduction velocities were within normal limits. Electromyography disclosed myopathic and neuropathic changes. Computed tomography (CT) of skeletal muscles showed asymmetrical muscle atrophy and patchy low-density foci. In biopsied left quadriceps and right gastrocnemius muscles which showed partially low density on CT, there was marked variation in muscle fiber size, with necrotic and regenerating fibers, an increased number of centrally placed nuclei, and interstitial fibrosis. There were numerous foci of mononuclear inflammatory cellular infiltration, especially around the blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301336 TI - [Neuron-specific enolase (NSE) and S-100b protein in cerebrospinal fluid of patients with cervical spondylosis--the relations with MRI findings and the changes of NSE and S-100b protein levels through Glisson's traction]. AB - We have previously reported that NSE and S-100b protein (S-100) could be used as reliable markers to evaluate the damage of the spinal cord in cervical spondylosis (CS) and ossification of posterior longitudinal ligament (OPLL). In the present study we made MRI in 21 patients with CS. There was a positive correlation between the NSE level in CSF and the degree of the spinal cord compression shown by MRI. In 10 cases of CS we examined these specific protein levels in CSF before and after the Glisson's traction therapy for one month. In seven of them the NSE levels decreased with the clinical improvements. On the other hand, 2 cases showed the rise of NSE levels after the traction. One of them became clinically worse during the therapy, while in another case the NSE levels changed within the normal range. The level of NSE in the other case was unchanged. In 57-year-old patient with CS myelopathy we examined the NSE levels chronologically. The NSE level changed in parallel with his clinical features. We suggest that NSE level in CSF may be a useful marker to estimate the change of the degree of the spinal cord damage in CS. PMID- 1301338 TI - [Manometry indexes for evaluating esophageal function in patients with achalasia]. AB - In 43 patients with achalasia (postoperative 18, post-dilatation 15, preoperative 10, and 10 normal people) esophageal manometry, esophageal emptying barium test and endoscopy were employed. The results showed that the esophageal emptying index EEI was 13.3 +/- 9.0 in the postoperative group, 4.7 +/- 7.6 in the post dilatation group, 50.0 +/- 17.4 in the normal group, 2.9 +/- 4.3 in the preoperative group. A linear relationship was seen between EEI and the lower esophageal barium retention area (So) (t = -5.00, P < 0.001). In patient with higher EEI and smaller So stronger esophageal emptying function was noted at swallowing. 80% of patients with less than 12 esophageal anti-reflux index (ARI) suffered from gastroesophageal reflux EEI and ARI can evaluate not only the esophageal motor functions but also the therapeutic effects of different treatment methods. The therapeutic effects are determined by esophageal peristalsis pressure and LES relaxation rate after LES is relaxed. PMID- 1301337 TI - [Esophageal manometry in patients with achalasia]. AB - Fifty-eight patients with achalasia were evaluated by esophageal manometry. In the body of the esophagus, the resting pressure was elevated and the motor waves were typically of low amplitude and presented simultaneously. The LES was of normal or high tone with absent or reduced relaxation in response to deglutition. The authors noticed that the contraction pressure in the pharynx and the resting and closing pressures in the UES were markedly elevated. These features were not documented in the literature. Twenty-two patients were followed up by manometry 4 to 60 months after a Heller's myotomy. The resting pressures in the body of the esophagus and the LES were obviously reduced. We considered that esophageal manometry is an important method in the diagnosis of achalasia. PMID- 1301339 TI - [The research and advances in esophageal electromyography]. PMID- 1301340 TI - [Multiple organ failure following severe acute pancreatitis: its clinically patterns and pathogenetic factors]. AB - To detect the clinical course and possible pathogenetic factors of multiple organ failure (MOF) after severe acute pancreatitis (SAP), we investigated retrospectively 70 consecutive patients with SAP for a 16-year period. Two different patterns of MOF were identified: rapid-single phase MOF developed early after SAP attack, and delayed tow-phase MOF developed progressively and sequentially with a lag phase. The clinical course of MOF was characterized by a severely systemic inflammatory response. Clinical variables associated with the evolution of MOF included early circulatory shock, pancreatic sepsis and severe pancreatic necrosis, which might be the leading one. It is suggested that the generalized inflammatory response triggered by the toxic focus seems to be the final common pathway linking SAP with MOF syndrome. PMID- 1301341 TI - [Gait analysis in patients with injuries of spinal cord and nerve root]. AB - In 102 normal subjects an IGI-3 gait analysis system was used to determine the normal level of walking. The results showed that the time of pressure appeared under foot and the sagittal joint movement of the lower extremities were similar to these reported previously. The forward and backward acceleration showed a single positive peak during swing phase, while the upward and downward acceleration showed two positive peaks. At heel contact of stance phase, the acceleration of all dimensions brought about a big negative peak. The variations in gait pattern were distinguished according to the curve characteristics and activity of muscles in the low extremities. The relations between the degrees of spinal cord injury and the gait characteristics were studied. The result indicated that the patterns of gait depend on the degree of injury. The more smooth acceleration curves, the better gait, and the abnormal gait is characterized by multiple peaks of pressure curves. PMID- 1301342 TI - [Intravesical BCG, mitomycin-C and thiotepa in the prevention of bladder tumor recurrence after operation]. AB - We observed the effects of intravesical irrigation with BCG (group B), Mitomycin C (group M), and Thiotepa (group T) in prophylaxis of bladder tumor recurrence after surgical treatment. Follow-up for 1-10 years showed that the recurrence rate of bladder tumor was 12.5% (3/24) in group B, 46.9% (15/33) in group M, and 61.8% (21/34) in group T respectively. The effect of BCG was far better than that Mitomycin-C and Thiotepa (P < 0.01). In 5 cases, who failed to Thiotepa, also showed satisfactory results after use of intravesical BCG. Considering the side effects of intravesical BCG, Thiotepa or Mitomycin-C should be used as the first choice of drugs in preventing the tumor recurrence. PMID- 1301343 TI - [Atypical adrenopathy]. AB - From 1985 to 1990, we treated 60 patients with adrenopathy, in which 4 (6.6%) had atypical adrenopathy. In the 4 patients, 1 showed Cushing's syndrome caused by an unilateral cortical adenoma and cortical hyperplasia on the contralateral side, 1 aldosteronism and pheochromocytomatic syndrome due to right cortical and medullary hyperplasia and a left cortical adenoma, 1 huge left nonfunctional cortical adenoma, and 1 pheochromocytomatic syndrome resulting from a cortical adenoma. The pathogenesis of the disease was discussed. PMID- 1301344 TI - [Photodynamic treatment of bladder cancer. Report of 117 cases]. AB - The clinical data on photodynamic treatment of bladder carcinoma in 117 patients confirmed that the treatment of bladder carcinoma of 1 cm to 2 cm in diameter may obtain better results. Carcinoma of 2-4 cm in diameter should be treated with increasing energy density and repeated exposure. If the carcinoma is larger than 4 cm in diameter or is involving the deep muscle and the cervix of the bladder, the treatment would be unsatisfactory. The tumor free rate in the 117 patients was 94%. The total recurrence rate was 30.1% after 8 years' follow-up. Finally, the indications for photodynamic treatment and the causes of recurrence were discussed. PMID- 1301345 TI - [Microneurovascular free abductor hallucis muscle transplantation for resuscitation of facial paralysis in one stage]. AB - After study of local anatomy in fresh cadaver the authors carried out free abductor hallucis muscle transplantation successfully in three patients with facial paralysis. In one patient the plantaris medialis vessels were anastomosed to the contralateral facial vessels and the plantaris medialis nerve was anastomosed to buccal branch of the contralateral facial nerve. In two patients the plantaris medialis vessels were anastomosed to the ipsilateral facial vessels and the plantaris medialis nerve was anastomosed to the myloidens branch from ipsilateral trigeminal nerve. The authors described the local anatomy and operative methods in details. The advantages of this operative method were also discussed. PMID- 1301346 TI - [Median thoracic flap with cartilage for repair of large tracheal defect]. AB - Large defect of the tracheal wall is very difficult to repair without support of cartilage. Two patients with large defect of the tracheal anterior wall (2.5-3.0 x 6.0 cm) were treated successfully. For the patients with much scar in neck a median thoracic flap (3.5 x 4.0 x 7.0 cm) was designed as follow: The flap was elevated, and 3 autocartilage bows (0.5 x 0.4 x 0.4 cm) were implanted into the separated tunnels just beneath the subdermal vascular plexus of the flap. The flap was sutured at the border of tracheal wall defect. The cartilage bows were fixed and covered with a combined cervico-thoracic and cervico-acromial bilobate flap. 13 cadavers showed that 1-2 stem vessels (n = 9) or 4-5 vascular branches (n = 4) developed in the flap. PMID- 1301347 TI - [Early pericardiectomy of acute purulent pericarditis]. AB - The results of early pericardiectomy in 15 cases of acute purulent pericarditis were reported. 13 cases were followed up from 2 to 8 years, none of them developed chronic constrictive pericarditis. The operation is simple and can shorten the time of hospitalization following thorough debridement of the infected foci. PMID- 1301348 TI - [Analysis of factors influencing on the surgical results of arterial embolism in the lower extremities]. AB - 130 patients with arterial embolism in the lower extremities underwent surgical treatment. The curative rate was 66.9%, amputation rate-19.2% and the mortality rate-13.8%. Statistical study showed that sex, age and recurrent embolism had few effects on the surgical results (P < 0.05). One of the influencing factors was the ischemic time of the lower extremities. The mortality rate was 33.3% in the distal abdomen with aortic embolism and 8.7% in the lower extremities (P < 0.005). The mortality rate and amputation rate were significantly higher in embolic patients with atherosclerotic stenosis and occlusion (9% and 17%). The mortality rate and amputation rate were 2.3% and 3.4% in patients with good blood flow and were 42.1% and 57.9% in patients without good blood flow uspectively. Reembolectomies showed no satisfactory effect. The results indicated that embolectomy combined with other necessary operations did not increase the mortality rate and amputation rate (P < 0.05). Postoperative anticoagulation therapy is extremely important. PMID- 1301349 TI - [Undesirable effects of drying on articular cartilage]. AB - Knee joints of mature rabbit were exposed to room air (room temperature 23 degrees C, humidity 63.5%) for a period ranging from 30 minutes to hours to imitate the human situation in operating room. The morphological findings indicated that the articular cartilage of the femur trochlea was moderately degenerated after 30 minutes of drying and obvious degeneration occurred two hours after operation. The articular cartilage of the patella also degenerated after two-hour drying. No necrosis was noted in the cartilage of the femoro tibial joint as that part could not be exposed thoroughly. It was possible to reduce the degenerative changes of articular cartilage if the joint was irrigated with Ringer's solution every 5 minutes. The results indicated that drying, a physical factor, can induce the degeneration of the articular cartilage. The longer the drying time, the more obvious the degenerative changes of cartilage; Ringer's solution is useful to prevent the degenerative changes. Clinically, the following points are worth considering: (1) Operating under arthroscope is much better than arthrotomy in avoiding the degenerative change of the cartilage; (2) The operating time should be as short as possible; (3) It is useful to irrigate the joint with some liquid to keep the joint surface moist; and (4) The consequence of exposure of the joint cartilage in cases of open injury of the joint must be seriously considered. PMID- 1301350 TI - [A study on knee joint geometry in Chinese: significance to prosthesis design]. AB - This study for the first time provided the geometric parameters of knee joints in Chinese, which are indispensable for the design of domestic knee prosthesis. Thirty five items, including linear, radial and angular measurements, were taken from 105 cadaver knees and knee X-ray films of 100 subjects. The method and calculation for proper correction of the X-ray image magnification and joint cartilage space was established. Correlation between the X-ray correction coefficients and the body weight was found to exist, and it formed the basis for individualized correction of X ray measurements. Statistical analysis revealed that most of the linear and radial measurements were highly related while the angular measurements were independent of others. Principal component analysis showed that the width of femoral condyle might be taken as the leading index in determining the dimension of the knee, and regression functions were established. Multivariate discriminate functions could aid the selection of knee prosthesis. PMID- 1301351 TI - The in vitro and in vivo biotransformation of N-deacetyl-N-formylcolchicine. AB - The major pathway of metabolic transformation of N-deacetyl-N-formylcolchicine is the oxidative cytochrome P450 dependent O-demethylation of substituents in the aromatic ring A and tropolone ring C. It was found that O-demethylation (both, in vitro and in vivo) takes place predominantly in the aromatic ring, especially at position 2. PMID- 1301352 TI - Hemodynamic effects on hepatic blood flow of a selective beta 2-adrenoceptor agonist, clenbuterol, in rat. AB - Acute clenbuterol administration (50 micrograms/kg, i.v.) to anesthetized normotensive rats, produce a marked reduction in the mean blood pressure, (MBP), about 58 mm Hg. Indocyanine Green clearance analysis (control, 1.83 +/- 0.15: clenbuterol, 1.10 +/- 0.20 ml/min/100 g, P < 0.05) showed that the action in the hepatic vascular bed is opposite to its systemic vasodilator effects. The hepatic blood flow (HBF) appears significantly reduced (control, 8.24 +/- 0.35: clenbuterol, 3.83 +/- 0.71 ml/min/100 g, P < 0.05) whereas the hepatic uptake and excretion proceedings were apparently not affected (control hepatic extraction coefficient, 0.225 +/- 0.024: clenbuterol, 0.300 +/- 0.04, NS). These findings show that a marked reduction in HBF follows systemic vasodilator effects produced by clenbuterol. PMID- 1301353 TI - Spectrophotometric quantification of astemizole and its demethylated metabolite in urine after TLC separation. AB - The coupling of TLC and UV measurement for determination of astemizole and its main metabolite, O-demethylated derivative, in urine has been investigated. The metabolite like the drug absorbs maximally at almost the same wavelengths, which makes their simultaneous UV determination in biological fluids quite inapplicable. TLC separation on silica gel F254 utilizing chloroform/methanol (85:15, v/v) achieved the best fractionation of the two compounds from the matrix components of urine. Concentration levels of 0.5-140 micrograms/ml (ppm) in worked-up sample could be reached by adopting the spectrophotometric measurements at 286 nm for ethanolic extracts of the silica layers carrying each individual compound against a blank silica. Varying levels of the intact drug and its phenolic primary metabolite could be accurately traced in urine samples following a 10 mg single oral dose (approximately 12.5 micrograms/kg) after different time intervals up to 12 h. Synthetic preparation of the metabolite by demethylating astemizole is mentioned and its physicochemical characterization is briefly discussed. PMID- 1301355 TI - The effect of felodipine on bile flow in pentobarbital anaesthetized rats and conscious rats receiving bile salt supplementation. AB - Felodipine, a vasoselective dihydropyridine calcium antagonist, has been given i.v. (0.2 mumol/kg) to anaesthetized and conscious male rats. There was no effect of pentobarbital anaesthesia on bile flow over a 6 h observation period. Felodipine increased the 6 h recovery of bile by approximately 25% in the conscious rat but in the anaesthetized rat there was a 20% decrease in bile flow following i.v. felodipine. A positive effect of Na-taurocholate infusion (1 mumol/min/100 g body weight) on bile flow in conscious rats was reinforced by concomitant felodipine dosing. Accumulated 6 h recoveries were 2.32 +/- 0.80 g/100 g body weight (control), 3.09 +/- 0.91 g/100 g body weight (taurocholate) and 5.00 +/- 0.80 g/100 g body weight. (taurocholate plus felodipine). The excretion of felodipine in the bile was significantly reduced during anaesthesia and during infusion of 2% bovine serum albumin (0.01 ml/min/100 g body weight) to conscious rats. PMID- 1301354 TI - The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. AB - Danshen is a Chinese folk medicine commonly used in the Chinese population. The effects of Danshen on the pharmacokinetics and pharmacodynamics of warfarin were studied in rats. In the pharmacokinetic study, single oral doses of warfarin were administered to rats or after 3 days treatment with Danshen intraperitoneally twice daily. Plasma warfarin concentrations were measured for 48 after each of two warfarin doses by high performance liquid chromatography (HPLC). In the pharmacodynamic study, the treatments were similar to the pharmacokinetic study, the prothrombin time (PT) was measured daily both in the Danshen treatment period and after the warfarin doses for 4 days. The absorption rate (Ka), volume of distribution (Vd) and elimination half-life (T1/2) of warfarin were significantly decreased while Cmax and Tmax were significantly increased after treatment with Danshen. There was no significant change in PT during the Danshen treatment period while the PTs were increased significantly in the first two days after warfarin doses. Our results suggested that Danshen can increase the initial bioavailability of warfarin and also affect the elimination of warfarin. It can also increase the PT further after the warfarin doses. The pharmacokinetic and pharmacodynamic interactions observed in this study indicate a clinically important interaction between Danshen and warfarin if these two agents are taken together. PMID- 1301357 TI - Pharmacokinetics of mefloquine in children aged 6 to 24 months. AB - The study was carried out in 12 children aged 6 months to 2 years, with uncomplicated falciparum malaria admitted to the Hospital for Tropical Diseases, Bangkok. They were treated with mefloquine in the form of MSP (mefloquine 250 mg+sulfadoxine 500 mg+pyrimethamine 25 mg) at a single dose of 25 mg mefloquine base/kg body weight. All of them were cured (28 days follow-up) with minimal side effects. Pharmacokinetic parameter determination was carried out in 9 cases. The results revealed that MRT, t1/2 and tmax in this study (children 6-24 months old) are comparable to the values in children aged 5-12 years, but shorter than in adult patients. Cmax and AUC in children 6-24 months old are comparable to those in children of 5-12 years, but much higher than in adult patients. Vz/f values in this study are comparable to those in children 5-12 years old, but lower than in adult patients. PMID- 1301356 TI - Pharmacokinetics of diltiazem and a new analogue, LR-A/113, in the conscious rat. AB - Pharmacokinetics and metabolism of diltiazem and a new analogue, LR-A/113, have been studied in the rat. Conscious rats, with the jugular vein cannulated, received the compounds by intravenous (3 mg/kg body weight) or oral (50 mg/kg body weight) route. Parent compounds and their N-demethyl and N-deacetyl metabolites were assayed at serial times in blood. Half-life of elimination of diltiazem was significantly shorter than that of LR-A/113, both after oral (37 +/ 9 vs 59 +/- 26 min) and intravenous (29 +/- 12 vs 57 +/- 16 min) administration. N-deacetyl-diltiazem concentrations after oral administration were higher than the parent compound and N-demethyldiltiazem; LR-A/113 blood concentrations were higher than those of its two metabolites. Metabolites were measurable only in traces after intravenous administration. Oral bioavailability was very low, 3.5% for diltiazem and 4.2% for LR-A/113. In conclusion, the substitution of a methyl by an isopropyl group appears to slow in vivo elimination of the analogue of diltiazem, LR-A/113. PMID- 1301358 TI - Pharmacokinetics, hydrolysis and aromatisation of norethisterone-3-oxime in female cynomolgus monkey. AB - Norethisterone-3-oxime (NETO) was administered to 3 female cynomolgus monkeys intragastrically and, after a wash-out period of 2-5 weeks, intravenously at a dose of 1 mg/kg. The radioactive dose of tritiated NETO was 20 microCi/kg for both treatments. For i.v. injection, a 30% propylene glycol/water solution and for i.g. administration an aqueous microcrystalline suspension was used. Excretion of radiolabel in urine and feces was followed for 5 days and plasma samples were obtained up to 2 days after administrations. In all samples (urine, feces and plasma) radioactivity was determined. Extracts from plasma samples were subjected to HPLC separation of drug and metabolites, as well as NETO and NET (metabolite of NETO after hydrolysis of the oxime group) levels were determined. In addition, EE2 (ethinylestradiol, A-ring aromatised metabolite of NET) levels were estimated using a specifically designed HPLC system for separation. Quantification of EE2 was achieved by radioimmunoassay (RIA) of specific eluate fractions. The results demonstrate that [3H]-NETO was absorbed completely at a dose level of 1 mg/kg, and excreted predominantly via the kidneys. A urinary to fecal excretion ratio of 1.5 (i.v.) or 1.0 (i.g.) was found. Renal excretion of total radiolabel proceeded with a half-life of about 0.8 (i.v.) or 1.1 (i.g.) days. Balances were incomplete, probably due to technical reasons. Orally administered NETO was highly bioavailable (84.0 +/- 16.9% of dose) but rapidly cleared from plasma (total clearance corresponded to 97% of plasma liver flow). The clearance from plasma is equivalent to the metabolic clearance because almost no unchanged NETO is excreted. Extensive metabolism of the parent drug was observed leading to at least two pharmacologically active metabolites (NET, EE2). The main progestogenic metabolite was NET reaching similar high plasma levels as NETO. EE2 turned out to be a metabolite of NETO and a conversion rate of below 0.5% of dose was estimated. However, due to its high estrogenic potency EE2 might contribute to the overall pharmacological pattern of NETO in the cynomolgus monkey. PMID- 1301359 TI - Pharmacokinetics of etodolac enantiomers in the rat after administration of phenobarbital or cimetidine. AB - The influences of phenobarbital and cimetidine on the pharmacokinetics of etodolac enantiomers were studied in male Sprague-Dawley rats. Phenobarbital caused significant reductions in the AUC of both the active S-enantiomer (24%) and the inactive R-enantiomer of etodolac (26%), and an increase in the urinary excretion of glucuronidated S-etodolac. In bile duct-cannulated rats the initial biliary recoveries of the acyl-glucuronidated etodolac enantiomers were not affected by phenobarbital. In vitro, phenobarbital caused no changes in the hepatic microsomal net glucuronidation of etodolac enantiomers after phenobarbital, although it did result in significant increases in the apparent oxidative metabolism of both enantiomers. Therefore, phenobarbital seems to cause an enhanced CL of etodolac by induction of hepatic non-conjugative metabolism. Cimetidine had no discernible effect on the pharmacokinetics of etodolac enantiomers. PMID- 1301360 TI - Pharmacokinetics of nefazodone in the dog following single oral administration. AB - The pharmacokinetics of nefazodone (NEF) and two of its pharmacologically active metabolites viz hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were determined following single oral administration of 100, 200 and 400 mg NEF to 6 beagle dogs in a three-way crossover study. Blood samples were collected for 48 h and plasma was analyzed for NEF, HO-NEF and mCPP by a validated HPLC assay. NEF was rapidly absorbed after oral administration. Cmax values for all three compounds and AUCinf values for HO-NEF and mCPP were dose-proportional; AUCinf values for NEF were dose-linear but not dose-proportional. The T1/2 values for NEF and HO-NEF following the 400 mg dose were significantly greater than those for the 100 mg dose. No differences in mCPP T1/2 were observed among the doses. The Cmax and AUCinf ratios for metabolite:NEF were about 2-fold lower for the 200 and 400 mg doses than those observed for the 100 mg dose. However, due to extensive variability, the ratios for three doses were not significantly different based on statistical analysis. Overall, these data suggest the pharmacokinetics of NEF are dose-dependent in the beagle dog. Statistical significance for dose-dependency for many of the pharmacokinetic parameters could not be demonstrated due to high variability associated with the plasma concentration vs time profiles. PMID- 1301361 TI - Pharmacokinetics of nefazodone following multiple escalating oral doses in the dog. AB - The single and multiple dose pharmacokinetics of nefazodone (NEF) were investigated in a dose-escalating study in which 4 beagle dogs (weighing approximately 10 kg) were orally administered 100 mg nefazodone hydrochloride on days 1-7, 500 mg on days 8-14 and 1000 mg on days 15-20 once daily. Serial blood samples were collected over a 24 h period following administration of the first (day 1) and last (day 7) doses for the 100 mg/day dose and the last dose for the 500 (day 14) and 1000 mg/day (day 20) doses. Blood samples were also collected for trough level (Cmin) determination on the morning of the 5th, 6th and 7th day of 100 and 500 mg/day dosing regimens and the 3rd, 5th and 6th day of 1000 mg/day regimen. Plasma was analyzed for NEF and 3 metabolites [hydroxynefazodone (HO NEF), m-chlorophenylpiperazine (mCPP) and p-hydroxynefazodone (p-HO-NEF)] by a validated HPLC assay. There were no significant differences between the 100 mg single and 100 mg/day multiple dose pharmacokinetic parameters for NEF, HO-NEF and mCPP. However, for p-HO-NEF, single dose elimination half life (T1/2) and area under the plasma concentration-time curve (AUC) extended to infinity were significantly smaller (P < or = 0.05) than the multiple dose T1/2 and AUCTAU, respectively. Based on Cmin data, steady state was reached by the 5th day of 500 mg/day and 1000 mg/day multiple dosing. Mean multiple dose AUCTAU values for NEF increased in a 1:9:26 ratio for a 1:5:10 increase in dose. Due to extensive variability and small number of animals used in the study, the statistical analysis indicated that AUCTAU values were dose-proportional. However, metabolite formation decreased significantly with increasing dose as indicated by AUCTAU ratios for metabolite:NEF. These data suggest that NEF exhibits nonlinear pharmacokinetics within 100-1000 mg/kg dose range in dogs. PMID- 1301362 TI - Electrical properties of neurons in the mediolateral part of the lateral septum: intracellular recordings from guinea-pig brain slices. AB - Membrane properties of 174 neurons were studied in the mediolateral part of the lateral septum (LSml) using an in vitro slice preparation of guinea-pig brain. Intracellular recordings were correlated with morphological data obtained from 34 neurons intracellularly stained with horseradish peroxidase (HRP). Neurons were divided into three classes according to their electrical responses. Class A and B neurons displayed the common property of an overshooting of spikes in response to the direct application of weak depolarizing current pulses. Class A neurons (59.2% of the total) generated tetrodotoxin-insensitive, high-threshold Ca2+ spikes in a control medium. Class B neurons (20.7% of the total) generated high threshold Ca2+ spikes only if tetraethylammonium was used to block delayed rectifying K+ current. Features common to class A and B neurons included the inactivation of Na+ conductance, the participation of high-threshold Ca2+ conductance in the generation of spikes--when repetitive discharges were elicited by strong depolarizing current pulses--and Cs(+)-sensitive, Ba(2+)-insensitive anomalous rectification. Class C neurons (20.1% of the total) displayed discharges comprising small-amplitude Na+ spikes followed by slow and large Ca2+ spikes, suggesting a locus of impalement which was not the soma. HRP-filled class B neurons (n = 5) were characterized by small to medium perikarya with spindly dendrites. The majority of HRP-filled class A (15/21) and all class C (n = 8) neurons showed large perikarya with thick primary dendrites and spiny dendritic branches. Thus, class A and C neurons typify the guinea-pig LSml in their morphological characteristics and in their ability to generate high-threshold Ca2+ spikes in a control medium. PMID- 1301363 TI - Peculiarities of inhibition in cat auditory cortex neurons evoked by tonal stimuli of various durations. AB - The extra- and intracellular responses of 262 neurons in A1 to tones of best frequency with durations ranging from 10 ms to 1.2 min were studied acute experiments on ketamine-anesthetized cats. Following the generation of action potentials in response to the tone stimulus, inhibition of both the background and the auditory stimulus-evoked spike activity were observed in 91% of the investigated neurons. The duration of this inhibition corresponded to the stimulus duration. For the remaining neurons (9%) an inhibition of the stimulus evoked spike activity alone was seen, also corresponding to the stimulus duration. Maximal inhibition of the spike activity occurred for the first 100-200 ms of the inhibitory response (the period which equalled the time of development of an IPSP in a cell). During this period of IPSP development, the membrane resistance of the neuron was reduced to 60-90% of its initial value. Varying the duration of the acoustic signal within a range of 10-200 ms was accompanied by a change in the IPSP duration and inhibition of the spike activity of the neuron. Whenever the tone lasted more than 200 ms, the membrane potential of the neuron was restored to the resting potential. However, during this period, the responsiveness of the neuron was lower than that initially observed. Measurement of the membrane resistance during the inhibitory pause that was not accompanied by hyperpolarization produced an index with an average 17% lower than the initial value for 87% of the neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301364 TI - Brain stem projections of rat lumbar dorsal root ganglia studied with choleragenoid conjugated horseradish peroxidase. AB - Brain stem projections from each of the L1-L6 lumbar dorsal root ganglia (DRGs) were investigated in adult rats following DRG injections of choleragenoid horseradish peroxidase. All these DRGs projected throughout the rostrocaudal extent of the gracile nucleus (Gr). Labeling from L1-L6 DRGs was transported to successively more dorsomedial areas of Gr. Investigation of the Gr projections from the DRGs revealed a somatotopic organization which was most prominent in the middle part of Gr. The cuneate nucleus showed smaller projections from all investigated DRGs. Minor projections to the internal basilar nucleus, external cuneate nucleus, medial vestibular nucleus, ventral cochlear nucleus and trigeminal sensory nuclei were also found from some of the DRGs. PMID- 1301365 TI - The influence of head position and head reorientation on the axis of eye rotation and the vestibular time constant during postrotatory nystagmus. AB - Reorienting the head with respect to gravity during the postrotatory period alters the time course of postrotatory nystagmus (PRN), hastening its decline and thereby reducing the calculated vestibular time constant. One explanation for this phenomenon is that the head reorientation results in a corresponding reorientation of the axis of eye rotation with respect to head coordinates. This possibility was investigated in 10 human subjects whose eye movements were monitored with a three-dimensional magnetic field - search - coil technique using a variety of head reorientation paradigms in a randomized order during PRN following the termination of a 90 degrees/s rotation about earth vertical. Average eye velocities were calculated over two time intervals: from 1 s to 2 s and from 7 s to 8 s after cessation of head rotation. The time constant was estimated as one third of the duration of PRN. For most conditions, a reorientation of the head with respect to gravity 2 s after the rotation had stopped did not significantly alter the direction of the eye velocity vector of PRN with respect to head coordinates. This strongly indicates that, in humans, PRN is mainly stabilized in head coordinates and not in space coordinates, even if the otolith input changes. This finding invalidates the notion that the shortening of PRN due to reorientation of the head could be due to a change of the eye velocity vector towards a direction (torsion), which is not detectable with the eye recording methods (electrooculography) used in earlier studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301366 TI - Effects of practice on final position reproduction. AB - Three subjects practiced fast, accurate 36 degrees elbow flexion movements to a 2.5 degrees target for 14 sessions of 100 trials (total, 1400 trials). Subjects then returned for a 15th experimental session in which they were asked to perform 15 movements under identical conditions to the practice condition. They were then tested under three experimental conditions without visual feedback: (1) identical to the practice conditions, (2) with small shifts in starting position (+/- 3 degrees of the practiced starting position), that were insufficient for subjective discrimination and, therefore, subjects were instructed to repeat the practiced movements; and (3) with a large shift in starting position (range, +/- 15 degrees of the practiced starting position), under the instruction to move to the same target. Experimental conditions 2 and 3 demonstrated that shifts in starting position were partially correlated with shifts in final position. These results are interpreted from the point of view of the equilibrium-point hypothesis of motor control. PMID- 1301367 TI - Viewing-distance invariance of movement detection. AB - Since visual movement information is often presented in electronic displays or films it is amazing that there is a paucity of research on the influence of viewing distance on motion detection in cinematograms. We report a relatively high degree of detection constancy with changing viewing distance for coherent motion in random-pixel cinematograms. A constant performance irrespective of viewing-distance is called 'distance-invariance' and for motion detection it proves to hold reasonably well for a relatively wide range of viewing distances both for foveal and eccentric vision. The limits of this viewing-distance invariance are explored as a function of screen velocity. Detection performance is quantified by a threshold signal-to-noise-ratio (SNR-) value, S, which is determined as a function of velocity for a range of viewing distances from 53 to 13,476 mm for foveal vision and from 60 to 1925 mm at 24 degrees eccentricity on the nasal horizontal meridian of the right eye's retina. The data can be explained, at least qualitatively, by a model in which a spatial-resolution stack has a stack of velocity-tuned motion detectors at every resolution layer. Such a 'stack-of-stacks' model is in line with proposals for contrast-detection stack models, but it suggests that the usual hypothesis that motion perception is based on the activity of two separate systems, the short-range and the long-range system, might be superfluous. This two-systems distinction was largely based on the different performance found for moving random dot patterns and moving form defined stimuli. A moving random pixel array viewed at very close range (e.g. 6 cm) presents the subject with relatively large almost square 'blobs', which are less dissimilar from the phi-stimuli used in classic motion perception studies than random dot stimuli at the usual medium to large viewing distances. It leads to maximum displacement threshold (Dm-) values that are not untypical of the 'long-range' system, but by gradually increasing the viewing-distance and thus decreasing the pixel-size a continuous change is found from typical long-range to typical short-range values of Dm. The two-systems distinction for motion detection appears to refer to the stimulus rather than to the visual system: The motion-detection system might be forced into a local or a global 'mode of operation' by the choice of stimulus. PMID- 1301369 TI - Does limb proprioception drift? AB - The hypothesis that proprioceptively perceived limb position drifts during visual occlusion was re-examined by combining some of the protocols used in previous experiments. Sixteen adult subjects made judgements of static limb position during visual occlusion lasting up to 2 min. In addition, the effect of brief 250 ms "glimpses" of the limb, occasional proprioceptive stimulation and directed attention were examined. Despite, conflicting evidence from earlier experiments, there was clear evidence of a drift in perceived limb position, towards the body, during visual occlusion. This drift was halted if brief glimpses of the limb were provided, or minor re-positioning (without vision) was allowed. In neither case, however, did the supplementary cues reset limb position to its originally perceived position. Drift was amplified when subjects attempted to attend to limb position rather than perform a secondary tracking task. The results are not easily accounted for if drift is considered purely as an effect of peripheral sensor adaptation. A notion of central-drift between visual and proprioceptive maps is suggested as an alternative hypothesis. PMID- 1301368 TI - Control strategies in directing the hand to moving targets. AB - We have evaluated the use of visual information about the movement of a target in two tasks--tracking and interceptions--involving multi-joint reaching movements with the arm. Target velocity was either varied in a pseudorandom order (random condition) or was kept constant (predictable condition) across trials. Response latency decreased as target velocity increased in each condition. A simple model that assumes that latency is the sum of two components--the time taken for target motion to be detected, and a fixed processing time--provides a good fit to the data. Results from a step-ramp experiment, in which the target stepped a small distance immediately preceding the onset of the ramp motion, were consistent with this model. The characteristics of the first 100 ms of the response depended on the amount of information about target motion available to the subject. In the tracking task with randomly varied target velocities, the initial changes in hand velocity were largely independent of target velocity. In contrast, when the velocity was predictable the initial hand velocity depended on target velocity. Analogously, the initial changes in the direction of hand motion in the interception task were independent of target velocity in the random condition, but depended on target velocity in the predictable condition. The time course for development of response dependence was estimated by controlling the amount of visual information about target velocity available to the subject before the onset of limb movement. The results suggest that when target velocity was random, hand movement started before visual motion processing was complete. The response was subsequently adjusted after target velocity was computed. Subjects displayed idiosyncratic strategies during the catch-up phase in the tracking task. The peak hand velocity depended on target velocity and was similar for all subjects. The time at which the peak occurred, in contrast, varied substantially among subjects. In the interception task the hand paths were straighter in the predictable than in the random condition. This appeared to be the result of making adjustments in movement direction in the former condition to correct for initially inappropriate responses. PMID- 1301370 TI - Differences between steady-state and transient post-synaptic potentials elicited by stimulation of the sural nerve. AB - In cat medial gastrocnemius motoneurons, single stimuli to the cutaneous sural nerve evoke a post-synaptic potential with a mixture of depolarization and hyperpolarization, depolarization being dominant in type F cells and hyperpolarization in type S cells. This pattern is consistent with previous reports showing that activation of the sural nerve can sometimes reverse the normal order of motor unit recruitment by inhibiting S motor units while simultaneously exciting F motor units. However, during repetitive stimulation for 1-2 s, we found that the hyperpolarizing component of the sural input to medial gastrocnemius motoneurons was not persistent, but instead gave way to depolarization after the first 30 ms. The net steady-state response after 0.5-1.0 s of stimulation was depolarization in all cells, regardless of motor unit type. This suggests that tonic sural input may be incapable of producing prolonged recruitment reversals. PMID- 1301371 TI - A mammalian model of optic-flow utilization in the control of locomotion. AB - Gibson (1966, 1979) and Lee (1976) have described the potential usefulness of optic-flow information for the control of locomotion. One variable that might be particularly important for an animal approaching a target is time-to-collision, which Lee argues is most efficiently specified by the tau margin (the inverse of the relative rate of expansion of the target image on the retina). In humans, most empirical studies of optic flow have required perceptual judgements or have examined catching/intercepting behaviours. In animals, most studies have been strictly observational. This is particularly true for mammals, where there has been no experimental work of any kind looking at the control of locomotion. The present experiment demonstrates that the Mongolian gerbil (Meriones unguiculatus) uses time-to-collision information to control deceleration as it runs towards a target. The development of this animal model will aid investigation of the neural circuitry underlying optic flow utilization in motor control. PMID- 1301372 TI - Understanding motor events: a neurophysiological study. AB - Neurons of the rostral part of inferior premotor cortex of the monkey discharge during goal-directed hand movements such as grasping, holding, and tearing. We report here that many of these neurons become active also when the monkey observes specific, meaningful hand movements performed by the experimenters. The effective experimenters' movements include among others placing or retrieving a piece of food from a table, grasping food from another experimenter's hand, and manipulating objects. There is always a clear link between the effective observed movement and that executed by the monkey and, often, only movements of the experimenter identical to those controlled by a given neuron are able to activate it. These findings indicate that premotor neurons can retrieve movements not only on the basis of stimulus characteristics, as previously described, but also on the basis of the meaning of the observed actions. PMID- 1301373 TI - Effects of neonatal removal of superior cervical ganglion on serotonin and thyrotropin-releasing hormone immunoreactivity in the intermediolateral cell column of the rat spinal cord. AB - In this study, we investigated the effects of the neonatal removal of the right superior cervical ganglion on the serotonin-like and thyrotropin-releasing hormone-like immunoreactivities (5-HT-LI and TRH-LI) in the intermediolateral cell column (IML) of the spinal cord by quantitative image analysis. Two weeks after the lesion, we observed a 60% reduction in 5-HT-LI, while TRH-LI was not significantly reduced, in the right IML (lesioned side) at T1-2 levels. One month after the lesion, 5-HT-LI and TRH-LI were significantly reduced by 60% in the right IML at T1-2 levels. After 3 months, this decrease persisted at this level. In addition, we observed a 30% loss of the 5-HT-LI in the right IML at T3-4 levels, whereas TRH-LI did not decrease significantly at T3-4 levels. These findings are discussed and compared with those of other experimental studies on serotonergic reorganization in the rat spinal cord. PMID- 1301374 TI - Collateral reinnervation and expansive regenerative reinnervation by sensory axons into "foreign" denervated skin: an immunohistochemical study in the rat. AB - Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S 100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100 IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into "foreign" denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1301375 TI - The fascicular organisation of the cat optic nerve. AB - Mammalian optic nerve axons are organised within a fascicular framework. This pattern changes between the eye and the chiasm. For most of the length of the nerve fascicular patterns are apparent, but close to the chiasm, in a region of major fibre rearrangement, the fascicular configuration is lost. It is not known how this change occurs, or whether there are less obvious systematic changes in the number of fascicles or their geometry along the length of the nerve. In this study these questions have been addressed at successive locations along the length of the cat optic nerve. The number of fascicles varied depending upon the location examined. A relatively high number were found behind the eye. The number declined in the mid-orbital portion before increasing again in the region of the optic canal. Further caudally there was a progressive change in the pattern of fasciculation, with a loss of fascicular structure medially. The remaining fascicles became concentrated around the inferotemporal periphery of the nerve. There was no fascicular organisation at the point at which the two nerves fused at the chiasm. Although the number of fascicles varied along the length of the nerve their geometric pattern did not change. PMID- 1301376 TI - Patterns of projections from area 2 of the sensory cortex to area 3a and to the motor cortex in cats. AB - Peripheral information reaches the motor cortex partly through corticocortical pathways that arise from two functional subdivisions, area 2 and area 3a, of the sensory cortex. These sensory areas are synaptically linked with one another. The patterns of connectivity and the different submodality input that each area receives suggest that they send different efferent signals to the motor cortex. The projections from area 2 to area 3a and to the motor cortex were studied with retrogradely transported fluorescent tracers. The pattern and distribution of neuronal labeling in area 2 was determined following injections of different tracers into the forelimb regions of area 3a and the motor cortex. The results showed that the projections from area 2 to the two target regions were topographically and somatotopically related. Multiple clusters of motor cortex projection neurons were found in area 2, and these clusters overlapped extensively with clusters of area 3a projection neurons. Although cells labeled with one of the dyes were often in close proximity to cells labeled with the other dye, no double-labeled cells were found. Two different laminar patterns were seen for the two populations of neurons. The projection to area 3a originated from cells located in layers II-III and layers V-VI. The projection to the motor cortex originated from cells spread throughout layers II-IV, but predominantly in layer III. Differences in laminar arrangement of the two populations of cells suggest a directional flow of information processing in the sensorimotor cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301377 TI - Differences in FM response correlate with morphology of neurons in the rat inferior colliculus. AB - The response characteristics to linear frequency sweeps were studied in two groups of FM (frequency modulation) sensitive neurons in the rat inferior colliculus. 'FM specialized' cells responded to frequency sweeps but not to pure tones. 'Mixed' cells responded to both frequency sweeps and pure tones. FM specialized cells preferred faster and broader sweeps of higher intensity than did mixed cells and were more directionally selective. In addition, FM specialized cells were more sharply tuned to FM velocity and FM range and had longer response latencies. Physiologically identified FM cells stained intracellularly with horseradish peroxidase revealed differences in morphology correlating with the differences in their responses to tones. FM specialized cells had larger dendritic fields, more dendritic branching and more dendritic spines than did mixed cells. The findings are taken as evidence that the two groups of inferior colliculus neurons are both functionally and morphologically distinct. PMID- 1301378 TI - Rapid increase in relaxin gene expression in early pregnancy in the pig. AB - Relaxin mRNA concentrations in porcine corpora lutea were examined during the peri-implantation period and throughout pregnancy using Northern and slot blot analysis. Total RNA was extracted from corpora lutea obtained from pigs of known breeding dates and pregnancy was confirmed by embryo recovery. A 32P-labelled porcine relaxin cDNA probe identified the 1.0 kilobase relaxin transcript. Slot blots were subsequently used to quantify relaxin mRNA concentrations. Relaxin mRNA was detectable in the corpus luteum of the regular cycle and was also present at similar low levels in corpora lutea of days 10, 11 and 12 of pregnancy. In corpora lutea from day 16 of pregnancy onwards 100-fold greater quantities of relaxin mRNA were observed. The intensity remained similar in samples between days 16 and 102 of pregnancy. These studies indicate that elevated relaxin gene expression commences very early in pregnancy and is first detectable in the peri-implantation period. PMID- 1301379 TI - Isolation of an insulin-like growth factor II cDNA from guinea pig liver: expression and developmental regulation. AB - Insulin-like growth factor II (IGF-II) cDNA was isolated from adult guinea pig liver by polymerase chain reaction (PCR) screening. A cDNA sequence was obtained corresponding to part of the preproIGF-II, including the signal peptide, the mature IGF-II and 37 amino acids of the acid carboxy-terminal E-domain. Amino acid sequence prediction, based on the cDNA clone, showed that mature guinea pig IGF-II has a high homology with both human and rat IGF-II, 100 and 94% identity, respectively. Levels of IGF-II mRNA in guinea pigs of different ages were analyzed by solution hybridization/RNase protection assay using part of the isolated IGF-II cDNA as a probe. There is a marked developmental regulation of IGF-II after birth. IGF-II mRNA levels were high in fetal livers, and decreased 15- to 30-fold in adults. As in man, but in contrast to rats, adult guinea pigs have significant levels of IGF-II mRNA in the liver. In fetal guinea pigs, the expression of IGF-II mRNA was 5-, 2- and 70-fold lower in kidney, skeletal muscle and brain cortex, respectively, than in liver. IGF-II mRNA levels in kidney and skeletal muscle of fetal guinea pigs were 5- and 4-fold higher, respectively, compared with adults. Similar sizes of IGF-II mRNA transcripts could be observed on Northern blots in newborn rats and in fetal guinea pigs. Our conclusions are that the mature IGF-II peptide in the guinea pig is 100% identical to the mature peptide in the human.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301380 TI - Effect of cold acclimation on the expression of glucose transporter Glut 4. AB - Glucose uptake by brown adipose tissue, measured following deoxyglucose injection in vivo, was increased by 6- and 11-fold following 2 and 14 days of cold exposure, respectively. To look for the possible mechanism of these modifications, the glucose transporter Glut 4 has been characterized at the protein and mRNA levels in brown adipose tissue, skeletal muscle and white adipose tissue following cold acclimation. Crude membranes were prepared from those tissues, and Glut 4 was studied by Western blot analysis. In brown adipose tissue, the total Glut 4 amount was increased by 52 +/- 7% and by 104 +/- 12% following 2 and 14 days of cold exposure, respectively. By contrast, in white adipose tissue of 14-day-cold-exposed mice the total Glut 4 content was decreased by 42 +/- 5%. However, Glut 4 concentration, expressed per mg of membrane protein, was unchanged in both brown and white adipose tissues following cold exposure, since the membrane protein content increased in brown but decreased in white adipose tissue. No modification in Glut 4 content was observed in skeletal muscle from cold-exposed mice. Total RNA were prepared and analyzed for Glut 4, glyceraldehyde phosphate dehydrogenase (GAPDH) and actin. Glut 4 and GAPDH mRNA were increased 2-fold in brown adipose tissue from cold-exposed mice, while actin mRNA content was unmodified. Glut 4 mRNA content was not changed in white adipose tissue and skeletal muscle from cold-exposed mice. Our results suggest that Glut 4 expression is differently modulated in the three insulin-responsive tissues during cold acclimation. PMID- 1301381 TI - Basal and gonadotrophin-releasing hormone-induced biosynthesis and release of luteinizing hormone: effect of calcium deprivation. AB - The present study examines the basal and gonadotrophin-releasing hormone (GnRH) stimulated biosynthesis and release of luteinizing hormone (LH) by pituitary cells in primary culture, and the effect of extracellular calcium deprivation on these events. Pituitaries from ovariectomized adult rats were enzymatically dispersed and cultured for 96 h. The cells were then incubated for 5 h (Expts. 1 and 3) or for different time intervals between 0 and 5 h (Expt. 2), in medium containing [14C]leucine ([14C]leu) and [3H]glucosamine ([3H]gln), with or without GnRH. Total immunoreactive LH (iLH) was measured in the medium and the cell extract by radioimmunoassay. LH translation (as estimated by [14C]leu incorporation into LH; [14C]LH) and LH glycosylation (as estimated by [3H]gln incorporation into LH; [3H]LH) were measured by immunoprecipitation with specific LH beta antiserum in both medium and cell extract. Treating the cells with GnRH caused both time- and dose-dependent increases of iLH in the medium as well as in total (cells plus medium) content, with an approximate ED50 of 0.7 nM. GnRH also stimulated LH biosynthesis by increasing both LH polypeptide chain synthesis and LH glycosylation. The effect of GnRH on LH glycosylation was detected earlier than that on translation, the [3H]LH rates of production and release being higher than those of [14C]LH. These findings suggest that GnRH-induced translation and glycosylation of LH are independently regulated. Removal of extracellular calcium resulted in the loss of cellular responsiveness to GnRH, preventing not only the stimulatory effects of GnRH on total and released iLH but also the GnRH-induced incorporation of both [14C]leu and [3H]gln into newly synthesized LH. These observations suggest that GnRH-stimulated LH glycosylation and LH translation involve calcium-dependent mechanisms. Neither the uptake of radiolabeled precursors nor their incorporation into total protein were affected by GnRH or Ca(2+)-deficient (no added calcium) medium. The results also suggest that the release of newly synthesized LH is regulated differently from previously synthesized stored hormone. PMID- 1301382 TI - The cloning of the human follicle stimulating hormone receptor and its expression in COS-7, CHO, and Y-1 cells. AB - Follicle stimulating hormone (FSH) receptor clones were isolated from a human testis cDNA library. Characterization of the cDNA clones showed that the DNA and predicted amino acid sequences of the long open reading frame differed from a previously published human ovarian FSH receptor sequence (Minegish et al. (1991) Biochem. Biophys. Res. Commun. 175, 1125-1130) by seven nucleotides and five amino acids. A human FSH receptor splice variant was also identified and characterized. A full-length human FSH receptor cDNA was engineered for expression in COS-7, CHO, and Y-1 cells. In transient transfections of COS-7 cells and stable transfections of Y-1 cells, efficient FSH receptor mRNA accumulation and isolation of FSH-responsive cell lines occurred only when an intron was included in the 5' untranslated region of the FSH receptor transcription unit. Y-1 cells stably transfected with the FSH receptor responded to FSH treatment by rounding up and by synthesizing increased amounts of progesterone. Stably transfected CHO cell lines, which responded to FSH by synthesizing increased amounts of cAMP, were isolated irrespective of the presence of the heterologous intron. The FSH-responsive CHO and Y-1 cell lines may be suitable for the development of better in vitro FSH bioassays. These cells also constitute a convenient source of human FSH receptor protein for use in radioreceptor assays and in studies of receptor-ligand interactions. PMID- 1301383 TI - Mouse submandibular glands express an androgen-regulated transcript encoding an acidic epididymal glycoprotein-like molecule. AB - Acidic epididymal glycoprotein (AEG) is an androgen-regulated, epididymal secretory protein assumed to be involved in sperm maturation. In the present study, we show that the mouse submandibular gland (SMG) expresses two genes designated Aeg-1 and Aeg-2. The nucleotide sequence of Aeg-1 cDNA clones was identical to that of epididymis-expressed Aeg cDNA clones, indicating that Aeg-1 is expressed in both epididymides and SMGs. The second, more abundant transcript, Aeg-2, had a sequence similar to, but distinct from, that of Aeg-1, and was not detectable in the epididymis. The level of Aeg-1 and Aeg-2 transcripts in the SMG was androgen-regulated and showed sexual dimorphism. In situ hybridization of SMG sections showed that Aeg-1 and Aeg-2 transcripts are produced by the cells of granular convoluted tubules. The C-terminal cysteine-rich region of the mouse AEG 2 molecule appears to have diverged faster than that of the mouse AEG-1 molecule, consistent with the idea that this region may play a role unique to the protein of the male reproductive system. PMID- 1301384 TI - Vasopressin biosynthesis in rodent Leydig cells. AB - Local biosynthesis of the peptide hormone vasopressin is demonstrated in vitro in Leydig cells derived from rat and mouse testis. Cycloheximide-sensitive production of the nonapeptide was shown for rat Leydig cells in primary culture. A polymerase chain reaction technique demonstrated the presence of functionally constituted vasopressin mRNA in rat and mouse testis, primary mouse Leydig cells and in rat and mouse Leydig tumour cell lines (MA10, R2C). Stimulation of cells with gonadotropins, however, had no effect either on peptide production or on levels of specific mRNA. Similarly, treatment of the MA10 cell line with a phorbol ester, or with rat atriopeptin, which activate other second messenger pathways, had no influence on vasopressin mRNA levels. The results are discussed in terms of an autocrine regulatory system which would provide the cell with information about its microenvironment. PMID- 1301385 TI - Regulation of the epididymal glutathione peroxidase-like protein in the mouse: dependence upon androgens and testicular factors. AB - The protein MEP24 was previously described as a glutathione peroxidase-like molecule specifically secreted by the mouse caput epididymidis. Recently, its binding to the head of spermatozoa was demonstrated. Here, the regulation of MEP24 expression was studied by analyzing transcriptional and translational activities in the epididymis (1) of adult mice castrated on day 60 and given various substitutive testosterone (T) treatments from day 90 and (2) of hemicastrated adult animals. In castrated mice, T treatment induced a significant rise in plasma T and 5 alpha-dihydrotestosterone (DHT) concentrations that greatly exceeded the control values. Owing to efficient regulation, however, the epididymal T and DHT levels were never higher than those of the controls. The restoration of MEP24 mRNA accumulation was complete when the epididymal DHT content returned to its normal value. However, when estimated in a cell-free system, the in vitro translatable MEP24 mRNA level never exceeded 70% of control values, even though the DHT and accumulated mRNAs were restored by 100% or more. In hemicastrates, the T content was normal on the castrated side, while the DHT content exhibited a significant decrease (47%). In this case, the MEP24 mRNA accumulation reached 88% of the normal value, but the translation rate, both in vitro and in vivo, was only about 50%. Ultrastructural studies showed that the normal rough endoplasmic reticulum organization in segment I cells is dependent upon the presence of testicular fluid in the epididymal duct lumen. Thus, this report shows that the MEP24 mRNA steady-state level is completely recovered in the presence of a normal epididymal DHT content, while restoration of the regulation of translation is just partial. This could be related to the cell organization but seems mainly dependent upon the presence of specific mRNA associated factors which are probably under the control of androgens and/or molecules carried by the testicular fluid. PMID- 1301386 TI - Divergent differentiation of rat adrenocortical cells is associated with an interruption of angiotensin II-mediated signal transduction. AB - The zones of the adrenal cortex contain distinct populations of cells which share a common developmental origin and steroidogenic template. In the rat, zona glomerulosa cells respond to angiotensin II (Ang II) with increased steroidogenesis while zona fasciculata/reticularis cells do not. We have examined Ang II-mediated signal transduction in homogeneous cellular sub-populations derived from either the zona glomerulosa (GLOM) or the zona fasciculata (FASC). In both of these sub-populations Ang II treatment significantly increased the levels of 3H-labelled inositol phosphates as well as the total mass of inositol 1,4,5-triphosphate. In contrast, the two cell types exhibited very different Ang II-mediated changes in free intracellular calcium ([Ca2+]i). Ang II (10 nM), induced [Ca2+]i increases of > 50 nM in 90% of individual GLOM cells (53/58), but in only 28% of FASC cells (11/39). These [Ca2+]i responses occurred after a transient Ang II stimulation ( < 1 min), in the presence of verapamil and in the absence of extracellular calcium, indicating an intracellular release. In small groups of 10-30 cells, stimulation with 1, 10 and 100 nM Ang II induced [Ca2+]i increases of 78, 178 and 215 nM respectively in GLOM cultures compared to only 35, 64, and 65 nM in FASC cultures. Thapsigargin treatment, which releases intracellular calcium in an inositol phosphate independent manner, elicited [Ca2+]i increases in both populations. Importantly, a calcium ionophore induced elevation of [Ca2+]i increased steroidogenesis in both cell types. These results suggest that an interruption of the signaling cascade at the level of intracellular calcium release contributes to the lack of a steroidogenic response to Ang II by the FASC cells. Therefore, in the rat adrenal cortex, divergent differentiation of related cell types may involve alterations within signal transduction pathways distal to initial receptor-mediated events (i.e. inositol phosphate production) and proximal to downstream effector events (i.e. steroidogenesis). PMID- 1301388 TI - The ups and downs of glucocorticoid physiology. Permissive and suppressive effects revisited. PMID- 1301387 TI - Developmental expression of hepatic growth hormone receptor and insulin-like growth factor-I mRNA in the chicken. AB - We have examined the ontogeny of expression of growth hormone (GH) receptor (GHR) and insulin-like growth factor-I (IGF-I) mRNA in chicken liver from day 13 of incubation until 31 weeks of age. The profiles of GHR and IGF-I mRNA levels were compared to developmental changes in body weight and plasma levels of GH and IGF I. In the embryo, hepatic GHR mRNA was not detectable until day 15, highest on days 17 and 19, and then declined at hatching (day 21). Following an initial 2 week delay after hatching, there was a progressive increase in hepatic GHR mRNA which continued after the birds reached mature body weight. Plasma GH reached peak levels at 3-4 weeks of age and then fell sharply until maintenance of a low basal level after 10 weeks of age. Thus, there appears to be a strong inverse relationship between expression of the GHR and basal plasma GH levels in the prepubertal chicken. Although IGF-I mRNA was undetectable in embryonic liver by Northern blot analysis, there is a good correlation between expression of hepatic IGF-I mRNA and the plasma IGF-I profile during post-hatching development in the chicken. The highest levels of IGF-I mRNA were reached at 4 weeks of age which was followed by a slow decline to the basal levels maintained after 10 weeks of age. It appears that the decline in plasma IGF-I lags considerably behind the sharp fall in plasma GH levels and expression of hepatic IGF-I mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301389 TI - Aldosterone action, and the cost of flame photometry. PMID- 1301390 TI - Localization of the heparin binding site of follistatin. AB - To define the heparin-binding site of follistatin, the reduced and S carboxymethylated recombinant human follistatin containing 288 amino acids was digested by Staphylococcus aureus V8. The digested product was subjected to sulfate cellufine column chromatography and the adsorbed peptide fragments eluted with a stepwise gradient of sodium chloride. The recovered column fractions were further purified by reversed-phase high-performance liquid chromatography (HPLC) and the HPLC peaks subjected to amino-terminal sequence analysis. All of the sulfate cellufine-retarded peptide fragments gave the same N-terminal amino acid sequence, which started at residue-68 of human follistatin, suggested that those fragments starting from residue-68 contain the heparin binding site. The multiple fragments might represent the oxidized, non-glycosylated or glycosylated forms of follistatin(68-113) resulting from the V8 digestion. A synthetic peptide corresponding to the region having the amino acid sequence 72-86 of follistatin was able to bind both heparin and sulfate cellufine, as well as compete with recombinant follistatin for binding to heparin. These findings further define the location of the heparin and heparan sulfate-binding site of follistatin at the basic amino acid-rich region comprising the amino acid sequence Lys75-Lys-Cys-Arg Met-Asn-Lys-Lys-Asn-Lys-Pro-Arg86. PMID- 1301391 TI - Variants of the 5'-untranslated sequence of human growth hormone receptor mRNA. AB - The human growth hormone receptor (GHR) gene was proposed to contain multiple 5' noncoding exons (Leung et al., 1987). The exact number and structure of these exons are unknown. As a first step in investigating this point more closely, we decided to clone alternative 5'-noncoding sequences of human liver GHR mRNA. The ligation-mediated single-sided polymerase chain reaction (PCR) was applied for selective amplification of 5'-terminal sequences of human liver GHR cDNA. PCR products were cloned and sequenced. Eight different sequence variants diverging in the 5'-untranslated regions beginning 12 base pairs upstream from the initiating ATG codon were found. One variant seems to represent unspliced or partially spliced GHR mRNA. The remaining variants probably correspond to multiple alternatively spliced forms of GHR mRNA. Homologs for three of these variants were found among previously published 5'-noncoding sequences of GHR cDNA obtained from other species by conventional cDNA cloning. Most of the cloned human liver GHR cDNA variants contain one or more ATG preceding the main GHR open reading frame start of translation. Thus, the GHR genes appeared to be a striking example of a very complex transcription unit. PMID- 1301392 TI - Transcriptional activity of a mutant thyroid hormone receptor beta in a family with generalized resistance to thyroid hormone. AB - We previously reported a family with generalized resistance to thyroid hormone (GRTH) which had a point mutation with codon 448 CCT (proline) being converted to ACT (threonine) in the thyroid hormone receptor (TR) beta. To characterize functional properties of the mutant TR beta, transient expression studies were performed in COS cells. A double stranded oligonucleotide encompassing thyroid hormone response element (TRE) derived from the rat GH gene was synthesized. We constructed chloramphenicol acetyl transferase (CAT) plasmid containing the thymidine kinase promoter under the control of the rat GH TRE. T3 induction of CAT activity by the mutant TR beta was significantly reduced as compared with that of the normal TR beta. This was observed in the presence of 0.5-50 nM T3, but not at 500 nM T3. When the normal and mutant TR beta were cotransfected, the mutant TR beta inhibited gene activation regulated by the normal TR beta. However, a high molar excess was necessary to significantly inhibit the function of the normal receptor. Additionally, the binding of in vitro synthesized mutant TR beta to TRE was preserved. PMID- 1301393 TI - Thyroid hormone regulates Ca(2+)-ATPase mRNA levels of sarcoplasmic reticulum during neonatal development of fast skeletal muscle. AB - In gastrocnemius muscle from newborn rats the mRNA for the fast sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform (SERCA1) comprised over 90% of total SR Ca(2+)-ATPase mRNA content and increased 5-fold between day 5 and 20 after birth, whereas in hypothyroid muscle the SERCA1 message level remained constant. Triiodothyronine (T3) treatment of 2-day-old euthyroid rats induced a precocious stimulation of SERCA1 mRNA levels, indicating that T3 is the determining factor in the stimulation of SERCA1 message levels and that this stimulation underlies the previously reported effect of the thyroid status on the neonatal development of SR Ca(2+)-ATPase activity. The low mRNA level for the slow SR Ca(2+)-ATPase isoform (SERCA2) was constant in both euthyroid and hypothyroid muscle development. Nevertheless, T3 treatment of hypothyroid neonates induced a transient stimulation of SERCA2 message levels, indicating that SERCA2 is responsive to higher levels of T3. PMID- 1301394 TI - Absence of direct regulation of prolactin cells by estradiol-17 beta in rainbow trout (Oncorhynchus mykiss). AB - The effects of estradiol-17 beta (E2) implants on plasma prolactin (PRL) concentrations, pituitary PRL content and pituitary PRL mRNA levels were examined in rainbow trout (Oncorhynchus mykiss). Intact immature fish treated with 1 mg estradiol-17 beta did not show significant changes in both PRL mRNA levels and pituitary PRL content after 3 days of treatment. In a similar experiment, no changes were observed in plasma PRL levels followed during 7 days. Similarly, lack of estradiol-17 beta effect on plasma PRL levels and on final PRL pituitary content was observed in ovariectomized female rainbow trout treated during 48 days with 25 mg estradiol-17 beta and in mature male fish over a 3-week treatment period. Localization of estradiol receptor (ER) mRNAs in the pituitary was carried out by Northern blot analysis using a full-length rainbow trout estrogen receptor (rtER) cDNA as a probe. The rostral pars distalis of the pituitary which contained mostly PRL cells showed the lower amount of rtER mRNA when compared to other parts of the pituitary. Moreover, two mRNAs of different size (3.5 and 1.4 kb) were detected in different parts of the pituitary. Further hybridization experiments using probes containing part of the rtER cDNA (E domain or C and D domains) indicated that the small-sized mRNA (1.4 kb) probably encodes a truncated ER protein lacking hormone binding domain or an ER-related protein. Thus, only the 3.56 kb mRNA appeared to be involved in the regulation of pituitary function by estradiol. In situ hybridization analysis allowed a more precise localization of this rtER mRNA in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301395 TI - Biosynthetic labeling of beta-hexosaminidase B: inhibition of the cellular uptake of lysosomal secretions containing [3H]hexosaminidase B by insulin-like growth factor-II in rat C6 glial cells. AB - The insulin-like growth factor-II/mannose-6-phosphate receptor binds two classes of ligands, IGF-II and lysosomal enzymes containing the mannose-6-phosphate recognition marker. To study the interaction of the two classes of ligands at the receptor level, we have isolated 'high uptake' forms of lysosomal enzymes containing mannose-6-phosphate that had been radiolabeled biosynthetically using a tissue culture model: Tay-Sachs disease fibroblasts were incubated in medium containing [3H]mannose, ammonium chloride and mannose-6-phosphate. Under the conditions of these experiments, the Tay-Sachs disease fibroblasts synthesized and secreted radiolabeled hexosaminidase B, as confirmed by measuring enzymatic activity of cell-conditioned medium. The enzyme secreted was recognized by antibodies raised against purified hexosaminidase A and B but not by nonimmune control sera in Western blotting and immunoprecipitation experiments. The radiolabeled cell-conditioned medium was partially purified by ion-exchange chromatography on a DEAE-Sephadex column. When partially purified [3H]hexosaminidase B was incubated with rat C6 glial cells which express large numbers of IGF-II/mannose-6-phosphate receptors, the enzyme was taken up specifically via the IGF-II/mannose-6-phosphate receptor as evidenced by carbohydrate competition experiments. The specific uptake of the radiolabeled lysosomal enzyme was partially inhibited by IGF-II and an antibody against the IGF-II/mannose-6-phosphate receptor (No. 3637). We conclude that the cellular uptake of a biosynthetically labeled lysosomal enzyme, hexosaminidase B, is partially inhibited by IGF-II. We hypothesize that IGF-II might be capable of modulating lysosomal pathways in vivo. PMID- 1301397 TI - Thyroid-specific and hormone-dependent expression of rat thyroglobulin promoter fused with bacterial chloramphenicol acetyltransferase gene in transgenic mice. AB - The minimal promoter of rat thyroglobulin (TG) gene (168 bp) was fused with bacterial chloramphenicol acetyltransferase (CAT) gene, and transgenic mice carrying the TGCAT gene were produced. The minimal promoter is sufficient for thyroid-specific and hormone-dependent expression of TGCAT in transgenic mice. Deletion of a region between -128 and -92 bp (TGII), which is not required for the expression of TGCAT in transient expression assays but whose sequence is most extensively conserved among different species, appears to decrease frequency of the expression of TGCAT in transgenic mice. However, the same deletion apparently has no significant effect on TG promoter activity in stably transformed rat FRTL 5 cells. PMID- 1301398 TI - Prolactin-induced protein kinase C activity in a mouse mammary cell line (NOG-8). AB - The normal mouse mammary epithelial cells, NOG-8, respond to the mitogenic signal of prolactin with a 2.5-fold increase in cell number within 3 days in vitro. When prolactin is added to subconfluent cells for 5-15 min, there is a 5-fold increase in protein kinase C activity. Upon longer exposure (24 h) to the hormone, the enzyme activity returns to that of control. The potent protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), blocks both the prolactin-induced enzyme activity and subsequent increase in cell number. Prior to prolactin treatment, 90% of the protein kinase C activity resides in the cytosol with only 10% associated with the membranes. After only 5 min of prolactin treatment, 70% of the enzyme activity is now localized to the membranes. These data suggest that prolactin uses the protein kinase C pathway for signal transduction in NOG-8 cells thus leading to enhanced cell growth. PMID- 1301396 TI - Prolactin stimulates transcription of aspartate aminotransferase in prostate cells. AB - Prolactin (PRL) has been reported to stimulate citrate production and the activity of mitochondrial aspartate aminotransferase (mAAT) and its precursor form pmAAT in prostate epithelial cells. The phorbol ester 12-O tetradecanoylphorbol 13-acetate (TPA) caused the same result as PRL, which suggests that the PRL effect on mAAT activity might be mediated by protein kinase C (PKC) stimulation of pmAAT gene transcription. Both PRL and TPA increased the level of pmAAT mRNA by 2.5- to 3-fold in pig prostate cells. The PKC inhibitor gossypol completely inhibited the PRL and TPA induced increases. In addition, the effects of both PRL and TPA were inhibited by down-regulation of prostate PKC. Nuclear run-off assays indicated that PRL and TPA induction of pmAAT occurred primarily at the transcriptional level. The stimulation of pmAAT transcription by TPA suggests that the pmAAT gene contains a TPA response element. Thus, these results are consistent with our previous observation that PRL directly induces pmAAT and that the mechanism of this PRL effect might involve stimulation of PKC. PMID- 1301399 TI - Insulin receptors and insulin-like growth factor I receptors in embryos from gastrula until organogenesis. AB - The demonstration of growth factor receptors in very young embryos is limited by the difficulty in obtaining sufficient tissue to yield adequate membrane preparations. We have developed an in situ binding technique that allowed quantitation of [125I]insulin and [125I]insulin-like growth factor-I (IGF-I) binding to individual chick embryos. Specific binding per embryo increased from the youngest stage studied (Hamburger and Hamilton (HH) stages 3-4, gastrulating embryo of approximately 18-20 h) until the third day of development. At all ages, the binding of [125I]IGF-I was several fold higher than the binding of [125I]insulin. Autophosphorylation of the beta-subunit of the receptors was stimulated by insulin and IGF-I in a stage- and dose-dependent manner. The two peptides did not have an additive effect. The present studies further support our previous data showing the early developmental appearance of insulin and IGF-I receptors, which very likely are essential for normal embryo development. In addition, this in situ method for demonstration of receptors can be applied to other types of receptors present in isolated organs and young embryos. PMID- 1301400 TI - An estrogen receptor positive MCF-7 clone that is resistant to antiestrogens and estradiol. AB - The antiestrogen tamoxifen has been successfully used to control estrogen receptor (ER) and progesterone receptor positive breast cancer. However, the development of antiestrogen resistance is frequently observed in patients following long term treatment. We have studied the development of antiestrogen resistance in vitro and established an antiestrogen resistant variant of MCF-7 cells (clone 5C) after long term culture in estrogen free medium. The growth of clone 5C cells was not altered by either estradiol-17 beta or the antiestrogens 4 hydroxytamoxifen and ICI 164,384. Estrogen-stimulated progesterone receptor and reporter gene expression were markedly reduced in 5C cells compared to wild type MCF-7 cells. Only minor alteration in the levels of ER and no alteration in the affinity of ER for ligand were found in 5C cells. No mutation of ER cDNA in 5C cells was detected by polymerase chain reaction and DNA sequencing. This study demonstrates that change(s) in ER-mediated gene expression rather than the amino acid sequence of the ER itself may be associated with the development of at least one form of antiestrogen resistance. PMID- 1301401 TI - Progesterone stimulates sulfate uptake in subcultured endometrial epithelial cells. AB - The effect of progesterone was studied on the sulfate entry in glandular epithelial cells of guinea-pig endometrium subcultured in bicameral chambers on matrix-coated filters in a chemically defined medium. At post-confluency (8 days of subculture), cells were treated with 10 nM estradiol alone or in association with various concentrations of progesterone. Optimal progesterone action was at a 16 h incubation time and a 10 nM hormonal concentration. Progesterone increased in a dose-dependent fashion the sulfate uptake specifically in glandular epithelial cells, preferentially from the basal surface. Progesterone effect on the sulfate uptake occurred only in estradiol-primed epithelial cells and was inhibited by the antiprogestin steroid RU-486. The progesterone-dependent increase in sulfate uptake was inhibited by the inhibitor of anion exchange, 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). At physiological sulfate concentrations, progesterone essentially induces a high-affinity DIDS-sensitive transport system. PMID- 1301402 TI - Phenotypic and proliferative properties of Schwann cells from nerves of diabetic patients. AB - The phenotypic (morphologic and antigenic) properties and mitotic index of cultured Schwann cells obtained by dissecting nerves from six diabetic patients were studied. These features were compared with those of Schwann cells cultured in vitro from six normal control nerves. Preservation of the specific antigenic properties of cells, identified with rabbit antiserum as bovine protein S-100, was documented by immunofluorescence with monoclonal antibodies against laminin, fibronectin, histocompatibility antigens HLA-A, B, C and -DR, HNK-1 antigen and the human receptor for nerve growth factor. The cell proliferation index was assessed by incorporation of bromodeoxyuridine. The results of the study showed that the mitotic capacities of Schwann cells from diabetic nerves cultured in vitro remained comparable with those of normal control cells. As regards phenotypic characteristics, no modifications were detectable by immunofluorescence. These findings suggest that the phenomena of demyelination and remyelination, sometimes with onion bulb features, which can be observed in some cases of diabetic neuropathy, are not due to a primary dysfunction of the Schwann cells but are secondary to axonal degeneration. PMID- 1301403 TI - Counteraction on experimentally induced diabetic neuropathy by levocarnitine acetyl. AB - The effect of levocarnitine acetyl on diabetic peripheral neuropathy induced by a single injection of streptozotocin or alloxan was studied. Levocarnitine acetyl was administered intraperitoneally one week after induction of diabetes at the dose of 50 mg/kg/day for five and ten weeks. At the end of treatment, neuromuscular conduction velocity (m/sec) was evaluated by stimulating the sciatic nerve and recording the soleus muscle potentials evoked, and the muscle contraction force (mm) by measuring the isometric muscular tension. Motor coordination was evaluated on the Rota-rod apparatus. Treatment with levocarnitine acetyl fully prevented the reduction (20%) in the neuromuscular conduction velocity observed in both experimental models of diabetes. The decrease (30-33%) in muscle contraction force was prevented partially in streptozotocin-induced diabetes and fully in alloxan-induced diabetes. Levocarnitine acetyl also improved the concomitantly reduced motor performance. The results of the present study suggest a beneficial effect of levocarnitine acetyl on peripheral neuropathy and muscle performance. PMID- 1301404 TI - Altered neuroexcitability in experimental diabetic neuropathy: effect of acetyl-L carnitine. AB - Sciatic nerve conduction velocity (NCV) is reduced in rats made hyperglycaemic with streptozotocin (STZ). This neurophysiological dysfunction has been associated with increased nerve sorbitol and reduced nerve inositol. Treatment of STZ diabetic rats with aldose reductase inhibitors (ARIs) which reduce sorbitol and increase inositol in the nerve results in normalization of NCVs. Male Wistar rats were made diabetic with 50 mg/kg of streptozotocin given intraperitoneally. Those animals with blood glucose > 300 mg/dl two weeks later were included in this study. The STZ-diabetic rats were treated with either the ARI sorbinil (40 mg/kg per day), or acetyl-L-carnitine (ALC) (300 mg/kg per day) or sterile 0.15% aqueous NaCl for 16 weeks after 4 or 8 weeks of untreated hyperglycaemia. A control group of non-diabetic rats received no treatment during the interval. Sciatic-nerve sorbitol was elevated (1.08 +/- 0.13 nanomol/mg wet weight vs. 0.19 +/- 0.03 nm/mg wet weight) and inositol was reduced (1.21 +/- 0.12 nm/mg ww vs. 2.02 +/- 0.08 nm/mg ww) in the STZ diabetic rats, which were untreated for 4 weeks. Treatment with sorbinil was associated with normalization of the tissue sorbitol (0.10 +/- 0.05 nm/mg ww), while ALC treatment also significantly reduced the nerve sorbitol but only to a level (0.34 +/- 0.08 nm/mg ww) more elevated than the normal level. The nerves of STZ animals treated with sorbinil or ALC had inositol levels no different from untreated diabetic rats. Thus, hyperglycaemic animals treated with either ALC or sorbinil had similar improvements in NCVs as the diabetic, even though the effect on nerve sorbitol was different and nerve inositol was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301405 TI - The roles of glucose-induced metabolic hypoxia and imbalances in carnitine metabolism in mediating diabetes-induced vascular dysfunction. AB - Investigations were initiated to examine the rate of imbalances in carnitine metabolism in the pathogenesis of diabetic vascular changes in the retina, peripheral nerves, aorta and kidney. It appears that glucose/diabetes-induced vascular dysfunction and early vascular structural changes are mediated by hyperglycaemic hypoxia i.e. glucose-induced metabolic imbalances that cause an increase in the reduced nicotinamide-adenine dinucleotide/nicotinic acid dehydrogenase ratio, and are linked to imbalances in carnitine metabolism. PMID- 1301406 TI - Morphological and electrophysiological changes of peripheral nerve-muscle unit in the aged rat prevented by levocarnitine acetyl. AB - The effects of levocarnitine acetyl on structure and function of the sciatic nerve and neuromuscular junctions of the soleus and extensor digitorum longus muscles were studied in the aged rat. To that end, neuromuscular conduction velocity (NMCV) was measured in vivo and morphological and morphometric evaluations were performed. Treatment with levocarnitine acetyl, 150 mg/kg day for six months, restored NMCV values to the levels measured in the young rat; significantly reduced the number of degenerating elements; and increased the number of myelinated fibres having normal structural features. In the soleus and extensor digitorum longus muscles, levocarnitine acetyl increased the complexity of neuromuscular junctions. These experimental findings suggest a neurotrophic action of levocarnitine acetyl on the peripheral nervous system that might have therapeutical applications in age-related peripheral nerve changes. PMID- 1301407 TI - Levocarnitine acetyl treatment promotes iris reinnervation following 6 hydroxydopamine-induced noradrenergic denervation in rats. AB - The effect of levocarnitine acetyl on neurite regeneration was evaluated following administration of 6-hydroxydopamine which caused a selective degeneration of peripheral catecholaminergic neurites in the irides of newborn and young rats. Levocarnitine acetyl 20 mg/kg body weight was administered either subcutaneously to newborn rats for 20 days or dissolved in drinking water to young rats for 90 days. Treatment with levocarnitine acetyl promoted neurite outgrowth following axotomy in both groups, thus demonstrating a stimulatory role of the substance in nerve regeneration of the peripheral nervous system. The results further confirm that levocarnitine acetyl is endowed with therapeutical efficacy in peripheral neuropathies. PMID- 1301408 TI - Levocarnitine acetyl prevents cell death following long-term section of the vagus nerve in rats. AB - Levocarnitine acetyl has previously been found to significantly prevent axotomy induced cell death in the spinal cord motor nucleus 9 and 12 months after section of the sciatic nerve in rats. In the present paper, the effects of levocarnitine acetyl on axotomy-induced cell death in the brain stem motor nuclei 90 days after section of the vagus nerve were studied. The right vagus nerve was cut at the neck. To prevent regeneration, a 5 mm-long segment of the vagus nerve was excised and the distal stump was displaced caudally. After surgery, a group of rats (n = 6) was treated with levocarnitine acetyl dissolved in the drinking water (75 mg/kg/day) (Group I). A second group of operated rats (n = 4) received drinking water alone. (Group II). Ninety days postoperatively, in the rats of both groups the proximal nerve stump of the vagus nerve was injected with horseradish peroxidase to label retrogradely the brain stem motoneurons of the dorsal motor vagal and the ambiguus nuclei. The brain stem nuclei were also labelled by horseradish peroxidase in three unoperated control rats (Group III). In the Group II rats, the number of horseradish peroxidase-labelled motoneurons of the dorsal motor vagal nucleus was found to be significantly smaller than in either the Group I (p < 0.01) or the Group III (p < 0.02) animals. In the Group I rats, the number of motoneurons of the dorsal motor vagal nucleus was not significantly smaller compared to the Group III rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301409 TI - Idiopathic facial paralysis: new therapeutic prospects with acetyl-L-carnitine. AB - The study population was composed of 43 patients affected by idiopathic facial paralysis (20 males and 23 females), aged between 11 and 67. The study was carried out in a double-blind, randomized, placebo controlled manner. Acetyl-L carnitine was given in an oral dose of 3 x 1 g daily for 1 month, along with a daily oral administration of 50 mg of methylprednisolone for 14 days. The evaluation was made by means of electromyograms (EMG) of the orbicularis oculi and oris muscles, by the Schirmes lacrimation test, by stapedial reflex test and a score scale for clinical assessment of paralysis. Results so far obtained have shown an earlier functional recovery of the nerve in those patients treated with acetyl-L-carnitine. Comparison between the affected and unaffected sides of the face revealed a statistical significance in the treated group (p < 0.05) as well as the amplitudes of the muscle action potentials (MAP) between the affected sides (p < 0.01). PMID- 1301410 TI - Reversible lung lesions in rats due to short-term exposure to ultrafine cobalt particles. AB - Using an ultrasonic nebulizer, cobalt aerosols (MMAD = 0.76 microns, sigma g = 2.1) were generated from an aqueous suspension of ultrafine metallic cobalt particles (Uf-Co) with a primary diameter of 20 nm. Rats were exposed to Uf-Co aerosols at 2.72 +/- 0.44 mg/m3 for 5 hours (Exp. 1) or at 2.12 +/- 0.55 mg/m3 for 4 days at 5 hours/day (Exp. 2). Only minimum histopathological changes were observed in the lungs in Exp. 1. In Exp. 2, evidence of slight injury was noted, including focal hypertrophy or proliferation of the epithelium in the lower airways, damages of macrophages, intracellular edema of the type I alveolar epithelium, interstitial edema, and proliferation of the type II alveolar epithelium. A new finding in this study was the morphological transformation of some damaged type I cells to the juvenile form, which appeared to indicate the capability of self-repair of this cell type. The return to a juvenile form seemed to be a key response of type I cells during the early process of repair without cell division following non-lethal injury. Cobalt accumulated in the lungs after inhalation and was transferred rapidly to the blood. In conclusion, inhaled Uf-Co induced reversible pulmonary injury even after short-term exposure. PMID- 1301411 TI - Measurement of urinary delta-aminolevulinic acid (ALA) by fluorometric HPLC and colorimetric methods. AB - We devised a fluorometric HPLC method for determining delta-aminolevulinic acid (ALA) in the urine of lead-exposed workers. With this fluorometric HPLC method and the conventional colorimetric method, the concentrations of urinary ALA in 84 lead workers were determined and compared. In the measurement of urinary ALA at lower levels (< or = 5 mg/1), the value of urinary ALA obtained by the fluorometric HPLC method was much lower than that obtained by the conventional colorimetric method, indicating that the colorimetric method also measures urinary ALA-like compounds such as aminoacetone. On the other hand, the measurement of urinary ALA at higher levels (> 5 mg/1) demonstrated that the ALA value obtained by the fluorometric HPLC method corresponded well with that of the conventional colorimetric method. A correlation coefficient between the fluorometric HPLC method and the colorimetric method was 0.856 for 60 urine samples with ALA < or = 5 mg/1, and 0.996 for 24 urine samples with ALA > 5 mg/1. PMID- 1301412 TI - Estimation of metallothionein synthesis in cadmium-exposed human lymphocytes by gel electrophoresis and silver staining. AB - Metallothionein (MT) is a low molecular weight metal-binding protein that is induced by a variety of heavy metals, and therefore is a candidate for an index in the biological monitoring of heavy metal exposure. As an approach to the establishment of a practical monitoring method, we estimated the MT levels in Cd exposed cultures of human peripheral blood mononuclear cells as well as purified lymphocytes using a technique developed for the electrophoretic analysis of MTs. By this procedure, we could successfully detect the MTs induced by Cd in a dose dependent manner. MTs were detectable even in cells exposed to as low as 0.5 microM Cd, which is close to the blood Cd levels of exposed workers. These results indicate the usefulness of this technique as a practical method for the monitoring of heavy metal exposure. PMID- 1301413 TI - Evaluation of mixed exposure to organic solvents by estimating their metabolites in urine. PMID- 1301414 TI - Pituitary-thyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: ontogeny of regulation of regulation and long-term programming of responses. AB - To evaluate the role of perinatal thyroid status in the development of pituitary thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH. PMID- 1301415 TI - The influence of gestational age and onset of labour on determinants of fetal maternal fluid and electrolyte balance in sheep. AB - Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se. PMID- 1301416 TI - Cerebral energy metabolism in immature and mature guinea pig fetuses during acute asphyxia. AB - In immature fetuses circulatory centralization caused by acute asphyxia is less effective than that in mature fetuses (Jensen & Berger, 1991). This suggests that cerebral oxygenation may be poor in immature fetuses during asphyxia. On the other hand cerebral oxygen consumption is lower in immature than that in mature fetuses. To determine, whether or not there is an imbalance between oxygen supply and demand in one or the other group, we compared the time course of the changes of cerebral concentrations of both high-energy phosphates and glycolytic intermediates between immature and mature guinea pig fetuses during acute asphyxia caused by arrest of uterine blood flow. The fall in the cerebral concentrations of adenosine triphosphate and glucose, and the rise in those of adenosine monophosphate and lactate were slower in immature than in mature fetuses. There were no differences between the levels of cerebral adenosine diphosphate and creatine phosphate of the two groups. From these results we conclude that during acute asphyxia the imbalance between cerebral oxygen supply and demand is less marked in immature than in mature fetuses. PMID- 1301417 TI - The development of gluconeogenic enzymes in the liver and kidney of fetal and newborn foals. AB - The activities of glucose-6-phosphatase (G6P), fructose diphosphatase, phosphoenolpyruvate carboxykinase (PEPCK), aspartate and alanine transferases were measured in liver and kidney of fetal foals between 100-318 days of gestation (term approximately 335 days) and during the immediate postnatal period (0-48 h after birth). All 5 enzymes could be detected in the fetal liver and kidney at the youngest gestational age studied. Mean fetal activities were lower than those observed in their mothers and showed no change with gestational age for the majority of enzymes studied. However, renal PEPCK and renal and hepatic G6P did increase towards term. At birth, hepatic and renal activities of these two enzymes were higher than those found in late gestation or in the adult animals. There was no apparent change in the activities of any of the other enzymes at birth. In late gestation (80-90% gestation), the activities of G6P and PEPCK in the foal were low compared to those in other species at the same stage of gestation. Similarly, the perinatal increase in enzyme activity occurred closer to term in the foal than in most other species. These observations indicate that maturation of glucogenic capacity occurs relatively late in the fetal foal and suggests that this process may be dependent on the prepartum rise in fetal cortisol as occurs in other species. PMID- 1301418 TI - Changes in the PR, RR intervals and ST waveform of the fetal lamb electrocardiogram with acute hypoxemia. AB - The PR and RR intervals and T wave amplitude of the fetal lamb electrocardiogram were studied during acute hypoxemia produced by reduction of the maternal placental blood flow. Five chronically-instrumented fetal lambs (124 to 143 days of gestation) were subjected to acute hypoxemia (observations = 13) through complete occlusion of the maternal aorta for 60 s. The fetuses responded to the occlusion with a fall in oxygen tension (2.18 +/- 0.12 kPa to 1.11 +/- 0.14 kPa, SEM, P < 0.001) and oxygen saturation (48 +/- 4% to 19 +/- 4%, P < 0.001). Modest changes of pH (7.37 +/- 0.05 to 7.35 +/- 0.01, p), carbon dioxide tension (5.79 +/- 0.15 kPa to 6.17 +/- 0.14 kPa, P < 0.001) and plasma lactate concentration (2.1 +/- 0.6 mmol/l to 2.2 +/- 0.6 mmol/l, ns) occurred. The PR interval showed a triphasic pattern following occlusion. Initially, and simultaneously with the onset of the RR interval lengthening, a prolongation of the PR interval occurred (P < 0.01) with a peak value after 41 +/- 3 s after occlusion. Following this transient prolongation, the PR interval shortened concurrently with a maximum lengthening of the RR interval (P < 0.001) 2 +/- 3 s after the end of the occlusion. A maximum PR shortening (P < 0.001) occurred 27 +/- 5 s after occlusion followed by a prolongation of the PR interval (P < 0.001) with a peak value 203 +/- 21 s after release of the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301419 TI - Effects of music preference and selection on stress reduction. AB - The use of music for therapeutic value has been documented throughout history. Modern research has identified specific types of music that seem to produce physiological benefits more consistently than others. The purpose of this research was to identify the effects of three types of music on perceived stress levels and to see if a correlation existed between music preference, music played, and stress reduction. Music preference was identified, stress level assessed, music played, and stress level was reassessed with 58 subjects. Paired t tests were statistically significant with two of the three musical styles. PMID- 1301420 TI - The relationship between health habits and health interests of students and employees in a nontraditional university. AB - This study investigated the health interests of students and full-time employees of a small, nontraditional university, and examined the relationships between selected health habits and correlated health interests. Health habits were assessed using the Wellness Check for Adults developed by the Rhode Island Health Department, and interest in health promotion programs was ascertained by the Health Interests Survey modified by the investigator. Significant (p < .05) differences between students and employees were found in their interest in 5 of the 11 health promotion programs listed. Responses to ranking 3 programs of most interest revealed that for students, exercising, weight control, and nutrition were prioritized, whereas employees ranked managing stress, nutrition, and weight control. Results of bivariate analyses (Mann-Whitney U) relating health habits to specific health interests varied in direction of association and significance. The results suggest a need to ask potential participants what health promotion programming they would be interested in attending rather than developing programs based only on identified health risk behaviors. Implications for further research are addressed. PMID- 1301421 TI - Therapeutic touch and post-Hurricane Hugo stress. AB - This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study. PMID- 1301422 TI - Intuition in nursing practice: deep connections. AB - The purpose of this study was to describe the phenomenon of intuition in nursing culture. The aims of the study were to (a) identify and describe terminology used with intuition in nursing care practice, (b) describe examples of experiential knowledge of intuition, (c) describe actions taken on intuitive experiences, (d) describe feelings associated with intuitive experience, and (e) compare and contrast patterns and processes of nursing intuition. The design of the study was ethnography. Sampling involved 40 nurses from all levels of the hospital and home health care practice. Intuition was found to (a) facilitate the depth of nurse client relationships; (b) lead to a deeper understanding and connection with client patterns; (c) be acknowledged as a professional risk; (d) emphasize the significant influence of autonomy, independence, and assertiveness in nursing practice; and (e) contribute to excellence in nursing care. Intuition was identified as a manifestation of transpersonal caring in the art of nursing practice and was deeply connected to caring as the moral ideal of the nursing profession. PMID- 1301423 TI - Innovative imagery: a health patterning modality for nursing practice. AB - The purpose of this study was to describe the phenomenon of intuition in nursing culture. The aims of the study were to (a) identify and describe terminology used with intuition in nursing care practice, (b) describe examples of experiential knowledge of intuition, (c) describe actions taken on intuitive experiences, (d) describe feelings associated with intuitive experience, and (e) compare and contrast patterns and processes of nursing intuition. The design of the study was ethnography. Sampling involved 40 nurses from all levels of the hospital and home health care practice. Intuition was found to (a) facilitate the depth of nurse client relationships; (b) lead to a deeper understanding and connection with client patterns; (c) be acknowledged as a professional risk; (d) emphasize the significant influence of autonomy, independence, and assertiveness in nursing practice; and (e) contribute to excellence in nursing care. Intuition was identified as a manifestation of transpersonal caring in the art of nursing practice and was deeply connected to caring as the moral ideal of the nursing profession. PMID- 1301424 TI - Using relaxation with guided imagery to assist primiparas in achieving maternal role attainment. AB - A framework has been developed that provides nurses with a theoretical basis for using relaxation with guided imagery with primiparas (first-time mothers) to reduce anxiety and depression and to increase self-esteem, thereby promoting maternal role attainment and expected infant behavior during the postpartum period. Although relaxation with guided imagery (RGI) has been used clinically in many situations, no research studies were found that reported using RGI with new mothers. However, because RGI has been effective in altering the responses of adults and children in diverse settings, it is inferred that RGI could be effectively used in helping primiparas adapt to the pressure of parenthood. An RGI protocol for use with new mothers is presented. PMID- 1301425 TI - The future of nursing in a technological age: computers, robots, and TLC. AB - The computer has become a major tool in the medical treatment of disease. Computers can record vital signs, keep records, and provide central networks for interactive diagnosis. Individual medical histories can be contained in an optical card the size of a credit card. Advances in technology just over the horizon will permit an individual to consult a computer much as one now consults a physician for diagnosis, recommendations, instructions, and treatment. Surgery can be conducted in "virtual space," with the physician operating inside the body (via computer) as if he or she were present at the site of the surgery. Only a step beyond this is the development of robots who can do a better surgical job than a human being. What is missing from this scenario? Tender loving care. That is the nurse's job, and it is something that computers cannot do because it involves feelings and human communication that are beyond mere technology. Consequently, nurses will be needed long after physicians have passed into limbo. The practical lesson of this look into the future is that, although nurses certainly must remain in touch with the cutting edge of technology, their primary purpose will be to retain and sharpen the skills that Florence Nightingale introduced. Human response will never be replaced by technology, and the unchanging need for the nurses' caring function will assure their future. PMID- 1301426 TI - A concept of holistic ethics for the health professional. AB - Holistic ethics involves a basic underlying concept of the unity and integral wholeness of all people and of all nature that is identified and pursued by finding unity and wholeness within the self. Within this framework, acts are not performed for the sake of law, precedent, or social norms, but rather out of a sense of doing good freely in order to witness, identify, and contribute to unity. The development of holistic ethics involves elements of both the masculine and feminine concepts interacting and relating to one another and encompassing traditional ethical views. It is characterized in the yin-yang mode of the monad of the East and the Western concept of masculine and feminine. Holistic ethics is not an ethics that is grounded or judged either in the act performed or in the distant consequences of the act, but rather in the conscious evolution of an enlightened individual of raised consciousness who performs the act. The concern is the effect of the act primarily on the individual and his or her larger Self (that unity of which he or she is a part). PMID- 1301427 TI - Plato's model of the psyche: a holistic model for nursing interventions. AB - Plato's theory about psychodynamic forces is used to develop a holistic model for nursing practice. The dysphoric emotional state of demoralization is conceptualized as an imbalance between Spirit, Appetite, and Reason. Interventions are designed for elderly clients who show objective and subjective signs of demoralization. The objective indicators are measured with the Psychiatric Epidemiological Research Interview (PERI), before and after the implementation of individualized interventions. Results for the 23 subjects who completed the study in an assisted-living environment are suggestive of the effectiveness of basic nursing interventions in remediating the symptoms of demoralization. Plato's model of the psyche is an elegant, yet simple, conceptual tool for understanding the mental health needs of clients. PMID- 1301428 TI - The ethics of caring: a basis for holistic care. AB - Interest in the concept of caring and the ethics of caring has grown as technology and depersonalization of health care delivery have increased. Major concepts of the ethics of caring are reviewed, with special focus on relating caring and virtue ethics. Assuming that caring is a virtue, it is concluded that ethically virtuous nurses must possess the caring attributes and demonstrate caring actions. PMID- 1301429 TI - Whose life is it anyway? Client autonomy. AB - The concept of individual autonomy, although generally valued in the abstract, is often negated in nursing practice. This is particularly true when the client's physical being is controlled by health care practitioners within an intensive care unit (ICU) setting. The concept of autonomy when applied to American health care practices clearly acknowledges in custom and law the right of the client to determine what treatment is acceptable and under what conditions. This article identifies some of the ethical dilemmas that arise in ICU settings and by a case example elucidates the implications for nursing practice. PMID- 1301430 TI - Community health and ethical theory: implications for holistic nursing. AB - A conceptual shift from Enlightenment philosophies to communitarian virtues is discussed. Epidemics and preventing disease spread are used as a basis for discussing the major bioethical concepts beneficence, justice, respect for autonomy, and Moskop's principle of restrictive measures. The addition of the concept of community and communitarian virtues to the ethical analysis is discussed. Holistic nurses are challenged to develop and employ morally sound rationale for ethical decisions. PMID- 1301431 TI - A commentary on language: persistent vegetative state--what's in a name? PMID- 1301432 TI - Teaching moral reasoning to student nurses. AB - Teaching moral reasoning to students is a challenge for all nursing educators. The National League for Nursing and American Nurses' Association emphasize the importance of ethical content within the curriculum. Review of the literature indicates that ethics has been part of the nursing curriculum since the early 1900s. However, the focus of nursing ethics has changed to more critical reflective thinking versus duties and etiquette. Educators have used a variety of methods for teaching ethics and integrating it into the curriculum. Yet nursing graduates still lack adequate skills to be morally accountable practitioners. This creates a dilemma for the educator to find ways to integrate more ethics content into an already crowded curriculum. The code of ethics of holistic nurses may serve as a basis to guide nurse educators in resolving some of the problems encountered in promoting moral education. PMID- 1301433 TI - Code of ethics for holistic nurses. Developed by the American Holistic Nurses' Association. PMID- 1301434 TI - [A simplified terminology for abnormalities of the lumbar disks]. AB - The terminology for abnormalities of the lumbar disk has always been a source of confusion. Recent advances in pathological studies have inspired the authors to propose a simple classification of common disk anomalies suitable not only for diagnostic radiologists but also for referring clinicians. Although the diagnosis of a few pathological entities will only be possible with specific imaging techniques, the proposed classification is appropriate for reporting observations from plain films, conventional tomograms, myelograms, discograms, computed tomography scans and magnetic resonance images. All lumbar disks can thus be classified into one or more of the following categories: normal, aging, scarred, ruptured and herniated. A disk herniation is defined as a localized exit of disk material beyond the limits of the original intervertebral space. PMID- 1301435 TI - [Intradural spinal cord lipoma. Apropos of 2 cases]. AB - The authors report two cases of intradural spinal cord. The first is located in the thoracic segment, the second has a cervico-thoracic seat. In the two cases these spinal cords lipoma are responsible for a progressive medullary compression. In this article the authors make a succinct review of the literature. They underline also the fundamental part of the MRI for the diagnosis and the injured balance sheet of the intradural spinal cord lipoma. PMID- 1301436 TI - [X-ray computed tomography of thoracic injuries. Apropos of 40 cases]. AB - On chest radiographs, the precise assessment of thoracic injuries consecutive to blunt trauma is often compromised by the nonspecific appearance of many lesions. Furthermore, significant injuries are frequently overlooked. However, the management of the patients with chest trauma is still often based primarily upon clinical and radiographic findings and Computed Tomography (CT) is often performed secondarily on the basis of unexplained clinical signs or suspected radiographic abnormality. Some authors have reported that CT was a highly sensitive method for detecting thoracic lesions frequently not seen or underestimated on conventional supine chest radiographs. However, the value that these new CT findings could have in the therapeutic management of these patients, have not been systematically investigated to our knowledge, except in a limited series suggesting that the course of critically ill patients could be substantially altered after thoracic CT. In order to estimate the role of early CT in the management of patient care, we report the therapeutic consequences of CT findings in forty patients who we report the therapeutic consequences of CT findings in forty patients who had a thoracic CT within few hours following a chest injury. We showed that early thoracic CT scan in patients with blunt trauma detected significantly more lesions than did chest X-Ray and appreciably modified the treatment modalities in 70% of our patients. We then recommend that all the patients admitted in ICU after chest trauma undergo a thoracic CT scan as soon as possible in order to optimize their treatment modalities. PMID- 1301437 TI - [Neoplastic involvement of pulmonary fissures. Diagnostic possibility of high resolution x-ray computed tomography]. AB - Acknowledging fissure invasion by pulmonary tumors located in contact with or in the vicinity of a fissure is an important piece of information for the therapeutic choice, especially in patients whose functional respiratory impairments are a contraindication of pneumonectomy. Fifteen patients with pulmonary neoplasms adjacent to a fissure were studied with standard computed tomography (10 mm sections), completed by high-resolution CT. The findings of the CT studies were compared with those operative reports. On surgery, the oblique fissure was infiltrated in 12 patients, unharmed in 2 others, while the horizontal fissure was infiltrated in 3 patients. Standard CT allowed diagnosing the involvement of the oblique fissure in 4 patients. Thin sections with high resolution reconstruction algorithms allowed detecting the involvement of the oblique fissure in 13 cases, including one false-positive result. On thin sections, the fissures appear as well-delineated, dense lines. This allows an accurate study of the relationships between the tumor and the fissure, thus increasing the sensitivity of CT for the detection of tumoral extension across the fissures. The orientation of the horizontal fissure, which is almost parallel to the plane of section, makes the study of its relationships with an adjacent mass difficult, even in high-resolution CT. PMID- 1301438 TI - [Desmoid tumor of the mesentery. An uncommon cause of ureteral obstruction]. AB - Desmoid tumors are rare lesions with a local invasive potential and a risk of recurrence considered as benign due to the absence of metastases. They are included in fibromatoses and may be associated with Gardner's syndrome. The authors report an unusual case, in a 26 year old man, of a desmoid tumor invading ileon, right colon, appendix and the right ureter and responsible of a ureteral obstruction. Etiologic factors (traumatic, hormonal, auto-immune...) are discussed. The treatment of choice to lower the risk of recurrence is the complete surgical removal of the tumor. PMID- 1301439 TI - [Radiological aspects of ileocecal tuberculosis. Apropos of 31 cases]. AB - The radiological diagnosis of ileo-cecal tuberculosis is based on the analysis of various and polymorph semiological signs. The authors report a series of 31 cases of ileo-cecal tuberculosis. The concomitant involvement of the ileum and the cecum il up to 61.2% of all cases. The associated peritoneal involvement is observed in 35.4% of the cases. The hypertrophic form is the most common (57%) and the ulcero-hypertrophic form in 43% cases. The observation of ileum short stenosis, valve attempt, cecum retraction, and associated peritoneal involvement is in favour of the ileo-cecal tuberculosis origin. PMID- 1301440 TI - [Human fascioliasis. Tomodensitometric aspects. Apropos of 2 cases]. AB - The authors report two cases of hepatic fascioliasis in which the CT scans of the liver revealed multiple hepatic low density lesions, better seen after intravenous bolus injection of contrast material. This CT signs may help in the diagnosis, follow up and to access the efficacy of hepatobiliary fascioliasis treatment. PMID- 1301441 TI - [Endovascular treatment of iatrogenic false aneurysm in the right subclavian pit. Apropos of a case]. AB - The authors report about one case of false aneurysm in the right subclavicular pit, which developed after iterative venous punctures in a 67-year-old woman. Surgery was excluded, and an endovascular treatment was decided, with an approach of the lesion by direct puncture in this case and the insertion of an inflatable balloon. PMID- 1301442 TI - [Endovascular treatment of iatrogenic arteriovenous fistula. Apropos of a case]. PMID- 1301443 TI - [MRI of normal spinal epidural fat]. AB - The authors perform a retrospective study of 65 spines examined with MRI. They specify the distribution of normal posterior epidural fat and establish the relationship between the anteroposterior thickness of epidural fat and the sagittal diameter of the spine on axial sections. On sagittal sections, the fat has a variable appearance, but a constant location along the spinal canal. PMID- 1301444 TI - [Accidental ultrasonographic disclosure of isolated intra-abdominal fetal hyperechogenicity. Apropos of a series of 87 cases]. AB - Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyperechogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra uterine deaths and one case of biliary duct atresia. PMID- 1301445 TI - [Echogenicity of blood]. AB - The echogenicity of blood is dependent of the back scattering of the ultra-sound beam by the flowing blood-stream. This black scattering is, according to the Rayleigh theory, proportional to the fourth power of the frequency and to the size of the particles. So, for the frequencies in clinical use, the size of the particles is essential. Micro bubbles and aggregates of red cells can be echogenic. Micro bubbles are scare. Echoes are mainly generated by blood cells aggregated from a given size for each wave length. For instance, 225 for 7.5 MHz frequency. High degree hematocrits and big molecules induce aggregation, but the main factor is the flow speed or more exactly the shear rate, i.e. 8/3 of speed/vessel radius. In clinical practice, blood becomes echogenic if flow slows and if the vessel radius increases. This happens for instance for venous or even arterial aneurysms, for dilated and dyskinetic cardiac cavities, an above all, in veins when flow slows. Echogenicity appears proximal to an organic or hemodynamic obstacle and is reversible when flow is restored. The technical conditions are important, too. Blood becomes more echogenic when the scan benears, the frequency increases and the resolution of the device goes higher. It can be expected that hemodynamic and even rheologic information will be obtainable in big vessels with computerized techniques quantifying blood echogenicity. Blood clots will be echogenic under the same conditions: red blood cells aggregated non hemolyzed. Their echogenicity appears more dependent of their structure than of the chronology. Better technical conditions will increase the clot echogenicity, too. Therapeutic and prognostic conclusions can be expected by better evaluation of prethrombotic stages and of structure of blood clots. PMID- 1301446 TI - Positive family history of glaucoma is a risk factor for increased IOP rather than glaucomatous optic nerve damage (POAG vs OH vs normal control). AB - To elucidate the family history of glaucoma (FHG) as a risk factor for ocular hypertension(OH) vs glaucomatous optic nerve damage, we reviewed the clinical records of 361 primary open-angle glaucoma(POAG) patients, 178 OH subjects, and 927 normal controls randomly selected from an urban medical center eye clinic. The prevalence of a positive FHG was 27% in the POAG patients, 47% in the OH subjects, and 11% in the normal controls. Whereas a positive FHG was a significant risk factor for both OH and glaucoma compared to normal control subjects (OR = 7.56, 95% CI: 5.27-10.85, P < .0001 for OH; OR = 3.15, 95% CI: 2.31-4.31, P < .0001), it was a risk factor more significantly for OH than for glaucoma being significantly more prevalent in OH than in POAG (OR = 2.40, 95% CI: 1.65-3.49, P < .0001). These results suggest the importance of additional risk factors other than IOP for glaucomatous optic nerve damage. PMID- 1301447 TI - The experimental Seoul-type keratoprosthesis. AB - The most important problem in the transplantation of artificial cornea is the extrusion of keratoprosthesis. So we performed this study to know the conditions to keep the keratoprosthesis as long as possible after animal experiment with experimental keratoprosthesis of various material and structure. We concluded from the results that silicone barrier could not prevent the retroprosthetic membrane, and fluorosilicone was not adequate material as an optic. And the following conditions are required to maintain keratoprosthesis as long as possible; optic made of PMMA, retention plate made of PTFE with 0.6 mm thick, anterior direction of optic, large optic, intralamellar suture technique. Furthermore we postulated that enzymatic theory is more appropriate than aseptic necrosis theory about the extrusion of keratoprosthesis. PMID- 1301449 TI - Electron microscopic study on overacting inferior oblique muscles. AB - Overaction of the inferior oblique(IO) muscle is manifested by elevation of the adducted eye and from the clinical point of view there are two types of overaction. The primary type is of unknown cause, whereas the secondary type is usually related to the palsy of the ipsilateral superior oblique or contralateral superior rectus. An ultrastructural study on the overacting IO muscles was performed compared to normal IO muscles by electron microscopy. Of 16 biopsies of overacting IO muscles, four had primary overacting inferior obliques and twelve had secondary overacting inferior obliques due to paralysis of superior oblique muscle. Additional four IO muscle, obtained from patients with intraocular diseases served as control specimens. The most striking abnormalities were aggregations of mitochondria and degenerating mitochondrial profiles and increased vacuolization in primary and secondary overacting muscles. Many muscle fibers were in different stages of atrophy, and hypertrophy and regeneration of muscle fibers were sometimes visible. The results suggest that the primary overacting IO muscle might be the result of a paresis of the superior oblique muscle. PMID- 1301448 TI - The use of cytosine arabinoside in glaucoma filtering surgery. AB - Posterior lip sclerectomies were performed in rabbits and cytosine arabinoside (Ara-C) was applied by topical instillation or subconjunctival injection. In both groups, the mean intraocular pressure (IOP) of the treated eyes was significantly lowered at postoperative week 1 and 2, but there was no significant difference between the mean IOP of the control eyes and that of the treated eyes at postoperative week 3 and 4. In both groups, at postoperative week 2, the sclerectomy sites of the control eyes were totally occluded by granulation tissue, but those of the treated eyes were partially replaced by granulation tissue. At postoperative week 4, the sclerectomy sites of the treated eyes were totally occluded by the granulation tissue ultimately in both groups. There were no differences in the mean IOP and the histologic finding of the treated eyes between the topical instillation group and the subconjunctival injection group. We concluded that either topical instillation or subconjunctival injection of Ara C can delay wound healing at the surgical site after glaucoma filtering surgery in rabbits. PMID- 1301450 TI - Reduction of postoperative adhesions in strabismus surgery. AB - An animal experiment was done to evaluate the efficacy of tissue coating with sodium hyaluronic acid and subconjunctival injection of triamcinolone acetate in reducing the severity of postoperative adhesions following strabismus surgery. Experimental animals underwent a mild traumatic surgical procedure in one superior rectus muscle and a severe traumatic surgical procedure in the other superior rectus muscle. Each group was divided into control group, sodium hyaluronate coating group and triamcinolone acetonide injection group. Grading the severity of adhesions through surgical exploration of operative sites and histological comparison after 4 weeks revealed a significant reduction of postoperative adhesions in sodium hyaluronate group compared with control group under conditions of severe surgical trauma. But triamcinolone groups have no significant differences compared with control groups by statistical analysis. Tissue protection afforded by sodium hyaluronate may lead to an effective method which minimizes the surgical trauma to the tissues and reduces the postsurgical adhesions following strabismus surgery. PMID- 1301451 TI - Radial keratotomy for the purpose of reducing glasses power in high myopia. AB - Anterior radial keratotomy for high myopia (over-6.25 diopter) to reduce refractive error was not able to dispense with glasses or contact lenses due to the high myopia itself. However patients could see objects well and were free of dizziness while wearing glasses of relatively reduced power. We performed anterior radial keratotomies on 83 high myopic and/or astigmatic eyes of 47 patients at Kangnam St. Mary's Hospital between May 1990 and Mar. 1991. Eight radial incisions with a diamond blade were performed and the Ruiz technique was added for astigmatism of over 2.0 diopters. The depth of incision was 90 to 95% of corneal thickness and the optical zone was 3mm in diameter. Patients were followed up on postoperative 7 days. 1 month, 3 months, 6 months, 1 year and thereafter. Uncorrected visual acuity of 20/40 or better after radial keratotomy could be obtained in 19.6% of high myopic eyes. A mean reduction of the spherical equivalent cycloplegic refraction of 5.13 diopters and a keratometric reading of 3.89 diopters after radial keratotomy were observed. About 90% of patients were satisfied with their visual outcome with reduced refractive power glasses. We recommend radial keratotomy for high myopic patients to reduce the refractive power and to help them enjoy a more comfortable life. PMID- 1301452 TI - Glaucoma risk factors in primary open-angle glaucoma patients compared to ocular hypertensives and control subjects. AB - To investigate the risk factors for glaucoma, we reviewed the clinical record of 361 primary open-angle glaucoma (POAG) patients, 178 ocular hypertensives (OH), and 927 controls without POAG or OH, randomly selected from an urban medical center eye clinic. Old age defined as > or = 55 year, (odds ratio ratio (OR) = 3.13 95% confidence interval (CI): 2.06-4.76, P < .0001), black race (OR = 2.58, 95% CI: 1.79-3.74, p < .0001), hypertension (OR = 1.709, 95% CI: 1.15-2.51, P < .0108), and diabetes mellitus (OR = 1.83, 95% CI: 1.08-3.09, P = .0308) were identified as significant risk factors in POAG compared to OH. Old Age (OR = 4.94, 95% CI: 3.62-6.76, p < .0001), and black race (OR = 2.04, 95% CI: 1.59 2.61, P < .0001), HTN (OR = 1.63, 95% CI: 1.26-2.11, P = .0002), and DM (OR = 1.40 95% CI: 1.02-1.92 P = .0450) were also significant risk factors when compared to normal controls. However, when the 361 POAG patients were compared to 361 controls matched with respect to age, race, and sex, hypertension and diabetes mellitus did not appear to be independent risk factors. Family history of glaucoma was found to be a risk factors more significantly for OH (OR = 6.79, 95% CI: 4.39-10.50, P < .0001) than for POAG (OR = 2.83, 95% CI: 1.90-4.21, P < .0001) compared to the matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301453 TI - [Concentration-effect and underestimation of time by acoustic stimuli]. AB - This experiment is to examine emotional effects induced by acoustic loading on time-estimation and degree of concentration on tasks. Subjects were ten college students, who were asked to produce five second periods (estimation of time), under acoustic loading for 15 minutes. Acoustic stimuli were (1) koto-music, (2) classical music, (3) sound effect, and (4) FM-noise, with different power spectra, expected to induce different emotions in the subjects. Time-estimation and EEG alpha-rhythm were used as parameters of concentration. The main results were as follows. In general, time was underestimated when the subjects' attention was concentrated on the tasks. Acoustic stimuli with 1/f-fluctuation and pleasant emotions induced underestimation of time. Gradient of fluctuation in time estimation also showed the same effects. With increase in acoustically induced pleasant emotions, alpha-rhythm increased, in parallel with the underestimation of time. These results suggest that emotions induced by the physical characteristics of acoustic stimuli affect mental concentration and eventually affect time-estimation. PMID- 1301454 TI - [A major factor of the decline in partial report performance with temporal delay]. AB - The purpose is to clarify what is the primary cause of decline in partial report performance due to cue delay over a given time period. Four subjects participated in the partial report task, and their performances were compared by using two types of stimuli: mixed-character matrix (alphabet, katakana, and kanji) and single-character matrix (one of the three characters), under the tachistoscopic presentation. Both matrices are arranged in three rows by four columns. The result was that the report performance declined almost equally as the cue delay increased under the mixed- and single-character matrix stimuli, even though the location confusion would not influence on the report in the mixed-character condition. Consequently, we may conclude that the decline in partial report performance was caused by the decay of identity information rather than that of location information. Further, the error trends revealed that the earlier researches using single kind of character stimulus (almost exclusively alphabet) overestimated the location error. PMID- 1301455 TI - [An experimental study on the determinants to the effects of self-affirmation]. AB - The purpose is twofold: first to examine whether an experience that affirms a valued aspect of the self eliminates the negativity of failure and second, to identify what is the most effective condition of self-affirmation. A 2 x 3 factorial design was employed: Immediately after having failed and prior to rating the beneficialness of failure experience, 72 subjects were allowed to affirm the real-self that they had built up, or the pseudo-self made by the experimenter. The situation of self-affirmation was (1) that subjects affirmed the self in private or (2) that the experimenter also affirmed the subject's self or (3) that the experimenter added information of another one who had the same aspect of self the subjects had affirmed. The self-affirmation effect was most clear-cut, when the real-self was affirmed, and was also affirmed by the experimenter. This effect was especially pronounced for high self-esteem subjects. Joint effects of high self-esteem, clearer real-self, and its publicity elevated level of self-affirmation. PMID- 1301456 TI - [Group theoretical approach to the cognition of transformational structures and goodness of patterns]. AB - In this article, we tried to reformulate the transformational structure theory of goodness judgment of patterns within the framework of the group theory. We found that reformulation based on the group concepts results in a more general theory, which we call the transformation group theory of goodness judgment of patterns. Main properties of the generalized theory are: 1. Each of the basic cognitive transformations is replaced by a transformation group. 2. They are the dihedral group consisting of mirror-image transformations and a cyclic transformation, the translation group, and the value-reversal transformation group. These groups are derivable independently of the given configurations. 3. The transformation group has the following properties: duality of invariance, non-divergency of transformations produced, and availability of indirect test of invariance. These properties are convenient for cognition of transformational structure of patterns in goodness judgment. 4. The intraconfigurational transformation structure of configurations can be defined by the transformation group so that order among goodness judgments can be predicted, in parallel with the existing transformational structure theory. PMID- 1301457 TI - [The effects of knowledge and its developmental differences on misconception of weight]. AB - This study aims to examine developmental knowledge related to misconception about weight. Subjects from 5th to 7th graders were asked to reason about justifiable phenomena which never occur in science. After that, before judging weight addition tasks, subjects engaged in some knowledge-generating-tasks to examine which knowledge-generating-tasks relate to misconception. The main results were as follows: (1) Most subjects did not realize untruth about justifiable phenomena, (2) the knowledge which related to misconception were muscular-kinetic feeling and balance-feeling about weight, and (3) awareness to knowledge generating-tasks changed with age; 5th graders found the relation about every kind of knowledge-task on chance level responding and 6th and 7th graders found the relation with some justifiable knowledge. Additionally, some 7th graders were not deluded by any knowledge-generating-tasks. These results suggested misconception about weight might relate to inference from some kinds of everyday knowledge without realizing the inconsistency with science to them. The developmental change of awareness to knowledge-generating-tasks were discussed in terms of coordination subjects' own theory and their use of knowledge. PMID- 1301458 TI - [A study on relationship between personality and self-acceptance]. AB - The purpose is to examine the relationship between self-acceptance and personalities developmentally, as for evaluative and affective dimensions. RESULTS: Males and females showed differences in the formation of adolescent self acceptance. At junior high school level, the accepted personalities are not yet differentiated as for two dimensions in both males and females. In males, they are differentiated at senior high school, and above this level, they showed a linear increase in differentiation. Females showed emotional differentiation at junior high school, and behavioral differentiation at senior high school, and further emotional differentiation at college level. The transition of male is "from a few limited to diverse", while for females it is "from diverse to a few limited". As the traits to self-acceptance diversify, the self-acceptance score is high. PMID- 1301459 TI - [Measurement of the feeling of knowing: norms of 216 general-information questions]. AB - The purpose of this study is to provide the normalized list of questions for investigating the feeling of knowing. Normative data were collected on 216 general-information questions from a wide variety of topics, including history, sports, art, literature, and so on. Three hundred and sixty-three undergraduates made a one-word response to each question, or rated their feeling of knowing on a 7-point scale if they could not recall any responses. The results showed that the questions distributed over a wide range on a scale of difficulty. There were few incorrect responses to the questions. Feeling-of-knowing ratings were moderately correlated with the probabilities of correct answers. These findings suggested that the questions provided in this study would serve for the research on the feeling of knowing. It was also suggested that the use of easier questions should generate a strong feeling of knowing. PMID- 1301460 TI - [Negative ideal-self as a standard of self-esteem]. AB - The concept of negative ideal-self is introduced as a contrast to positive ideal self. Discrepancies between positive ideal-self and real-self (Dp-score) have been associated with low self-esteem. The present study purported to see whether negative ideal-self may be a standard of self evaluation, and to what extent discrepancies between negative ideal-self and real-self (Dn-score) relate with self-esteem (Rosenberg). The results showed that both Dp-score and Dn-score correlate significantly with self-esteem, but the latter showed higher correlation than the former. It is suggested that self-esteem is more a function of distance that how 'I' am not the person which 'I' want to be. These findings were discussed from the importance of an approach to negative aspects of the self. PMID- 1301461 TI - [The effects of subconscious processing of anger-related words and physiological arousal on the emotion of anger and aggressive behavior]. AB - An experiment was conducted to examine the effects of the prior subconscious processing of anger-related words and physiological arousal upon anger and aggressive behavior in a frustrated person. Sixteen male and 24 female college students participated in the experiment. First, the subjects performed a cognitive task in which they processed anger-related words or neutral words subconsciously in the high arousal or normal arousal state. In the second ostensibly unrelated task, the subjects were presented with a frustration story and they were asked to rate the intensity of anger which the victim in the story would feel, the victim's responses, and impressions of the frustrator, on several SD-trait scales. It was found that the subjects who processed anger-related words in high arousal state rated the victim as being in the most intense anger and aggressive in behavior and reported the impression of the frustrator as most negative. These findings were interpreted in terms of the network model of emotion. PMID- 1301462 TI - [Face recognition in preschool children: effects of familiarity, facial expression and angle of view]. AB - The purpose of this study was to investigate the face recognition processes in preschool children. Two experiments were carried out to examine the effects, on face recognition, of familiarity, facial expression and angle of view of faces as well as changes or no changes in facial expression and/or angle of view occurring between the first presentation and the subsequent recognition test. The subjects were 188 five- and six-year old children. In Experiments 1 and 2, half of the faces were highly familiar to the subjects, and the remaining half unfamiliar to them. In Experiment 1, the facial expressions (e.g., smiling or serious) were either changed or unchanged. In Experiment 2, the facial expressions or angles of view (e.g., full-face views or three-quarter views of faces) were either changed or unchanged. The major findings were that the familiar faces and the smiling faces were recognized more correctly than the unfamiliar faces and the serious faces respectively. The results were discussed in terms of 'identity-specific semantic codes' and 'visually-derived semantic codes'. PMID- 1301463 TI - [Perception of odor quality by Free Image-Association Test]. AB - A method was devised for evaluating odor quality. Subjects were requested to freely describe the images elicited by smelling odors. This test was named the "Free Image-Association Test (FIT)". The test was applied for 20 flavors of various foods, five odors from the standards of T&T olfactometer (Japanese standard olfactory test), butter of yak milk, and incense from Lamaism temples. The words for expressing imagery were analyzed by multidimensional scaling and cluster analysis. Seven clusters of odors were obtained. The feature of these clusters were quite similar to that of primary odors which have been suggested by previous studies. However, the clustering of odors can not be explained on the basis of the primary-odor theory, but the information processing theory originally proposed by Miller (1956). These results support the usefulness of the Free Image-Association Test for investigating odor perception based on the images associated with odors. PMID- 1301464 TI - [Influences of environmental-context changes on rehearsal effects in episodic memory]. AB - Does rehearsal facilitate association between to-be-remembered items and environmental context (EC) as well as it strengthen the individual traces of items? The answer from the present experiment was affirmative. Subjects, 183 undergraduates, studied a list of 15 familiar nouns by rehearsing aloud with a subsidiary task, and then received a free recall test under one of three conditions: immediate recall (IM), same context (SC), and different context (DC). Subjects in IM were tested immediately after the study session, while the other subjects were tested 24 hours after the study session. The tests in IM and SC were conducted at the same place with the same experimenter after the same subsidiary task as the study session, whereas the test in DC were conducted at a different place with a different experimenter without the task. The magnitudes in DC of the effect of the number of rehearsals on free recall were about one-half of those in IM and SC, whereas the magnitudes in IM were nearly identical to those in SC. The results indicate that the rehearsal effect is one of EC dependent phenomena. PMID- 1301465 TI - [Apparent depth by the stereograms without binocular retinal disparity: is Lau effect artifact?]. AB - We examined the idea that, when the Zollner figure in one eye and the principal lines in the figure in the other eye were presented, the perceived depth is due to "phenomenal" disparity. The phenomenal disparity is defined as apparent displacement between two illusory "oblique" principal lines in one eye and two "parallel" principal lines in the other. Observes were asked whether depth was seen or not at upper or lower part of the two perceived lines and, if seen, which line was closer. Seventeen observers showed that only 9% of their responses was consistent with the idea, although they reported depths for disparity stimuli. This suggests that the dichoptic presentation of such figures should not be considered as that requires the processing of binocular disparity. PMID- 1301466 TI - [A study on HTP organic signs]. AB - A special version of the House-Tree-Person (H-T-P) technique was developed to differentiate organic psychosis from other disorders. H-T-P data of 126 psychiatric inpatients, including 16 patients with organic psychoses, 50 schizophrenics, 50 borderlines and 10 patients with other psychoses, were evaluated for the presence or absence of 29 possible features of houses, trees and persons. These features included those common to all three objects, as well as those specific to each object. Results for patients with organic psychoses were compared with those of patients with other disorders. The comparison disclosed that seven of the original 29 H-T-P features had diagnostical discrimination among treatment groups, giving higher H-T-P organic scores. PMID- 1301467 TI - [Influences of motor disability on the development of scene concepts]. AB - Two studies were conducted to investigate the influence of motor disability of the child on cognitive development. In Study I, elementary school teachers and undergraduate students were requested to rank the school subjects according to how much the teaching of each subject would facilitate scene concepts development of children. The results visually represented by the rank graphs indicated that "physical training" and "arts" which require body actions and movements were judged to be most important for scene concepts development. In Study II, both normal and physically handicapped children were asked to perform free recalls to each of the three stimuli: "my house," "my school," and "my town." The results showed the influence of the size of space implied by the stimuli on the number of the items recalled by healthy children but this influence was not the same with physically handicapped children. These results, which indicate the importance of body actions and movements for scene concepts development, were discussed in terms of education for physically handicapped children. PMID- 1301468 TI - [Effects of self-efficacy and outcome expectation on observational learning of altruistic behavior]. AB - The purpose of the present study was to examined the hypothesis that the effects of observational learning of altruistic behavior are related to personal viewpoint, self-efficacy, outcome expectation, and other factors. One hundred and fifty-five fourth-grade school children were assigned randomly to four conditions; distress viewpoint, outcome expectation, altruistic behavior, or non observational control. After observational learning, the students were immediately administered the generalization test of altruistic behavior, empathy, reward and punishment expectations, and rating tests of self-efficacy belief. It was found that; (a) altruistic behavior and outcome expectation conditions had significant learning effects, (b) self-efficacy was able to predict altruistic response in the altruistic behavior viewpoint condition, and (c) from an outcome expectation viewpoint, altruistic behavior toward peers and adults related to punishment expectation, whereas social sharing was related to reward expectation. According to these findings, an observational learning model of altruistic behavior was proposed. PMID- 1301469 TI - [An investigation of the recognition process for jukugo by use of priming paradigms]. AB - Three experiments were conducted to examine the recognition process of the jukugo (two-kanji-compound word) from the following three points of view: (1) how jukugos are retrieved from memory (Exp. 1), (2) how jukugos are activated in the retrieval process (Exp. 2), and (3) how the representation of jukugos is structured in memory (Exp. 3). The experiments were carried out using priming paradigms in which subjects performed a lexical decision task. The results of Exp. 1 and Exp. 2 showed that the first kanji was used as retrieval cue for each jukugo and the activation of the first kanji facilitated the identification of jukugo in terms of meaning. In Exp. 3, it was suggested that the lexicon of jukugo was formed in such a structure that several jukugos containing in common the same first kanji are tied together, centering on the first kanji. PMID- 1301470 TI - [The relationship between evaluation of school stressors and stress responses in junior high school students]. AB - The purpose of this study is to develop a school stressor scale from the events experienced frequently by junior high school students in their daily school life, and to examine the relationship between school stressors and stress responses. In study I, factor analysis of data by 552 students revealed four main factors "teacher", "friend", "club activity", and "study", which were extracted from initial set of 72 items. In study II, factor analysis of 50 items, of which 39 items were extracted in study I, and 11 new items of free-description type, of data by 622 students, revealed that main stressors in junior high school were following six, "teacher", "friend", "club activity", "study", "rule", and "official activity". Furthermore, multiple regression analyses revealed that "friend" strikingly correlated with "depressive-anxious emotion" and "study" did with "cognition-thought of helplessness". PMID- 1301471 TI - [Effects of conversation act on conversation strategy and interpersonal cognition]. AB - It is assumed that dyadic conversation proceed according to some of each participants' conversation strategies. The strategies are as follows; 1) Receptivity, 2) Emotional expressivity, 3) Cognitive expressivity, 4) Partner comprehension, 5) Contingent comprehension, 6) Self-assertivity. In this experiment, strategies and interpersonal cognition were manipulated by three factors, (1) partners' conversation acts, with high or low expressivity rule, and (2) high or low act of conversation performance rule, and (3) nature of topica. One hundred and twenty-eight undergraduates are asked to rate their level of intention to select a strategy, in a given conversation situation. The results are as follows: 1) Both cognition of conversational purpose for a given situation and partners' expressivity influenced on their conversation strategy, 2) correspondence of strategy prompt participants to active conversation, 3) partners' conversation acts influenced on interpersonal cognition in any situations, 4) social desirabililty in interpersonal cognition is influenced by both strategy and topic, 5) partners' strategy makes participants select different interaction in the subsequent conversation situation. PMID- 1301472 TI - [Effects of between-item elaboration on incidental memory]. AB - The present study was carried out to investigate the effect of between-item elaboration on incidental memory of words. Between-item elaboration refers to the encoding of relational information to each target item. Forty-four college students were asked to generate free associates to each target in the orienting task which was followed by unexpected recognition and recall tests. Triplets of targets which was known to elicit a converging associate were used. Targets of such a triplet were presented in massed or spaced fashion. Frequency of converging associates generated in the orienting task (free association) was used as an index of between-item elaboration. The proportion of targets correctly recalled for which the converging associates were generated was higher than that of the opposite cases. The above result suggested that the between-item elaboration was effective in retrieval of targets. No effect of types of presentation on free recall performance was observed. PMID- 1301473 TI - [An examination of Metzger's theory on geometrical illusions by using the illusion of major and minor axes in ellipse]. AB - An experiment with ellipses was conducted to evaluate the validity of Metzger's theory on geometrical illusions (the law of good Gestalt) by examining whether its major axis is underestimated and its minor axis overestimated. If the horizontal or vertical dimension of a circle with a fixed diameter is reduced, " smaller" ellipses with major axes equal to the circle's diameter will be constructed. On the other hand, if the dimension is enlarged, "larger" ellipses with minor axes equal to the circle's diameter will be produced. Ten university students estimated the apparent lengths of such axes. It was found that the major axes were underestimated, while the minor axes were overestimated, irrespective of the relative sizes of the ellipses. The same result was obtained when the orientation of the axis was rotated 90 degrees. These results may be interpreted in line with Metzger's theory to the illusion of major and minor axes in ellipse. PMID- 1301474 TI - [An examination of self-monitoring as a determinant of compliant conforming behaviour]. AB - The present study investigated the determinant of compliant conforming behaviour from the view-point of the self-monitoring. Subjects, who were classified into High Self-Monitors (HSM) and Low Self-Monitors (LSM), participated in the experiment in which they had a task to distinguish the size of two circles. About the half of subjects performed the task with confederates. In eight of 13 trials, confederates had mistaken distinctions intentionally. The results showed HSM were more conformable to confederates than LSM for male subjects. HSM seemed to conform themselves to confederates easily, because their behaviour was guided by external cues. By contrast, LSM would conform themselves with difficulty, because their behaviour was guided by their internal states. But there were no significant differences for female subjects, and the ability of self-monitoring was considered as the less explanatory determinant for conformity in this experiment. PMID- 1301475 TI - [Effect of stimulus intensity on visual stream segregation]. AB - Two experiments were performed to examine the effect of stimulus intensity on VISS (visual stream segregation) which is a kind of beta movement first described by Bregman and Achim (1973). Six subjects were required to find the upper threshold of ISI for producing VISS under various conditions of the stimulus intensity in each experiment. The ISI threshold decreased as the stimulus intensity was increased. The result showed that VISS follows Korte's second law of apparent motion. When two of the four lights were flashed in high intensity and the rest in low intensity, the ISI thresholds varied with the arrangement of intensity among the four lights (stimulus intensity pattern). The results suggest that VISS is affected by the factor of similarity resulting from the intensity patterns of the lights. PMID- 1301476 TI - Maternal tasks of uncertain motherhood. AB - A longitudinal, phenomenological study was carried out to gain understanding of what it was like for women to be in a high-risk perinatal situation. Twenty-seven women participated in the study during which focused, unstructured interviews were conducted throughout their experience. Hermeneutic methods were applied to the 174 interviews and 13 diaries collected. A serendipitous finding revealed that women in high-risk situations work on the same developmental tasks as described by Rubin in 1975. However, these tasks are altered by the uncertainty of attaining motherhood inherent in the high-risk situation. The alterations in the tasks are described in this paper. The importance of Rubin's work as basic clinical research for maternity nursing is underlined by this finding. PMID- 1301477 TI - Thermoregulation and axillary temperature measurements in neonates: a review of the literature. AB - The theoretical and empirical literature were reviewed to examine the current knowledge about thermoregulation and temperature-measurement techniques in neonates. The results indicate that there is a conflict in the literature regarding the length of time needed to obtain neonatal axillary temperature measurements with glass thermometers and a gap in the literature pertaining to the symmetry of axillary temperature measurements in neonates not exposed to an external heat source. Liquid crystal and tympanic thermometers have been demonstrated to be inaccurate fever detectors. The use of electronic thermometers may offer nurses time-saving alternatives to standard glass thermometers for obtaining neonatal temperature measurements. PMID- 1301478 TI - Changes in father-infant bonding beliefs across couples' first transition to parenthood. AB - Thirty-five couples expecting their first child served as subjects in a study of changes in beliefs concerning father-infant bonding experienced by individuals and couples across the transition to parenthood. Through a series of open-ended interviews and structured questionnaire measures, it was determined that the typical first-time father and mother undergo significant drops in their beliefs about the importance of father-infant bonding across their first transition to parenthood. Regression analyses were employed to construct models predictive of changes in parents' father-infant bonding beliefs. Results indicate that both prenatal beliefs and circumstances of the delivery predict changes in parents' father-infant bonding beliefs. Implications for childbirth educators, delivery staff, and parent support providers are discussed. PMID- 1301479 TI - The effect of leukemia and its treatment on self-esteem of school-age children. AB - The purpose of this research was to investigate the self-esteem of school-age children with leukemia in a clinic setting and to compare it to the self-esteem of healthy children. Thirteen chronically ill children, 6 to 11 years old, who were patients at a midwestern clinic and children's hospital, and 50 school-age children without chronic illness participated in the study. Children were administered the Kinetic Family Drawing-Revised (Spinetta, McLaren, Fox, & Sparta, 1981) to measure their self-image in relation to their family. Children's self-esteem was measured by the Coopersmith Self-Esteem Inventory (SEI) (Coopersmith, 1981). The results indicated that children with leukemia did not differ in self-esteem from healthy children except on one subscale of the SEI. However, children with and without leukemia did differ on components of the self image measure, a dimension of self-esteem. Implications of the findings are discussed. PMID- 1301481 TI - [The update findings on the celiac disease]. PMID- 1301480 TI - Quality of life in school-age children following liver transplantation. AB - A descriptive exploratory study was conducted to ascertain the quality of life in school-age children 3 to 6 years following liver transplantation for chronic liver disease. Thirty children were to be included, however only 25 were recruited, and 20 of the 25 children became the study sample. The 20 school-age children ranged in age from 5 years 4 months to 11 years 9 months. The setting for the study was a conference room adjoining a social work office in a 220-bed university-affiliated children's hospital located in a large city in the Northeastern United States. The data were collected through the use of individual interviews, which were audiotaped and transcribed, and the written completion of an 80-item, self-report inventory. Interviews ranged in length from 1 hour 15 minutes to 1 hour 45 minutes. They were scheduled at a time that was convenient to the children's yearly pediatrician follow-up examination. Since the children and their families lived in other states and countries a great distance from the hospital, all communication with the families and scheduling of appointments were coordinated by the secretary of the pediatrician. The children in this study experienced liver transplantation 3 to 6 years prior to the interview for biliary atresia (n = 15), alpha 1-antitrypsin deficiency (n = 3), tyrosinemia (n = 1), and neonatal hepatitis (n = 1). Eighty-five percent of the children (n = 17) experienced liver transplantation before the age of 6 years, and 15 percent of the children (n = 3) experienced transplantation after 6 years of age. Responses from the modified Pigem's test, a projective test of children's values and attributes about self, and from the Zamberlan Questionnaire were content analyzed, then categorized according to the specific areas representative of the children's evaluation of the quality of life. Interrater reliability of the categories demonstrated 87% agreement of the coded items on the interview data. Five categories were derived from analysis of the interview and Pigem's data and included: (a) psychosocial adjustment at school and relationships with peers and family members; (b) internalization of the donor organ, the knowledge of the liver transplant experience, and thoughts about the donor person; (c) changes in physical appearance and physical functioning; (d) emotions, fears, or concerns about rejection and future outcome of the liver transplant(s); and (e) children's satisfaction with present and future life, and thoughts about self as reflected on the Pigem's test.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1301482 TI - [Hodgkin's disease in childhood]. AB - Only in these latest years has been possible to consider Hodgkin disease (HD) as a neoplastic syndrome, thank of immunohistochemistry and cytogenetic techniques which have confirmed the monoclonal origin of typical cellular marker of disease: the Reed-Sternberg cell (R-S cell). Interesting associations have been observed between children suffering from HD and the positivity of EBV antigen above all in the socio-economically developed countries. The histopathologic classification of HD is divided in four sub-types, with different incidence in the pediatric age: the nodular sclerosis and the mixed cellularity are more rap-presented than the lymphocyte predominance and mostly the lymphocyte depletion. Histopathologic classification is essential for the prognosis and a correct therapeutic approach to disease. The management of HD is based on chemotherapy and radiotherapy associated; the results of treatment are more and more encouraging with a global survival over 95%. Sequelae of treatment are reduced in modern therapeutic trials: in particularly injury to somatic growth, cardiopulmonary system, gonadal and thyroid functionality is reduced by using low dose and involved fields for the early stage patients. The most important sequela in children treated for HD is the risk to developed a second malignant neoplasm; in particularly acute nonlymphocytic leukemia and non Hodgkin's lymphoma. In patients treated with radiotherapy alone increase the risk to develop solid tumors like sarcomas and carcinomas, which can appears several years after diagnosis. PMID- 1301483 TI - [The early high-dose immunoglobulin treatment of neonatal autoimmune thrombocytopenia]. AB - The paper reports the case of a neonate suffering from autoimmune neonatal thrombocytopenia whose mother had suffered from previous idiopathic thrombocytopenia purpura. Although asymptomatic, the baby received early treatment with high doses of immunoglobulin G (1 g/kg) in a single dose. Treatment was repeated on day 12 using the same method. No other treatment was associated with IgG. The Authors confirm the good level of tolerability and efficacy of IgG in the treatment of autoimmune neonatal thrombocytopenia without complications. PMID- 1301484 TI - [Long lasting conjunctivitis: research of etiological factors]. AB - Forty children with long-lasting or recurrent conjunctivitis were included in this etiological study. It is well known that purulent conjunctivitis is mainly bacterial, with a major source of infection from Chlamydia; recently, however, a greater percentage of viral forms, with the exception of conjunctivitis without secretion, has been reported. The authors focused their attention on the clinical symptoms and on bacteriological studies of the forms of Chlamydia and Mycoplasma conjunctivitis, highlighting their marked sensitivity to antibiotics and the clinical response and recommending the importance of an etiological study in all cases in which conjunctivitis does not resolve within a short period of time. PMID- 1301485 TI - [Clinical and cellular studies in a patient with Cockayne syndrome]. AB - Hypersensitivity to the lethal effect of ultraviolet light (UV) and other DNA damaging agents has been observed in cells from patients affected by Cockayne syndrome, suggesting that this syndrome is deficient in the capability to repair damage in cellular DNA. We report a case showing the main clinical features of Cockayne syndrome in which the clinical and cellular photosensitivity described as typical for Cockayne syndrome is not present. These cytological results suggest that there is considerable clinical and cellular heterogeneity in Cockayne syndrome and that cellular sensitivity to UV might not be as essential for the diagnosis of Cockayne syndrome as previously thought. PMID- 1301486 TI - [Poland syndrome]. AB - A case of Poland's syndrome in a newborn is described. The syndrome is relatively unknown, especially in its epidemiological and aetiopathogenetic aspects. It's characterized by aplasia of the sternal head of the pectoral major muscle, hypoplasia of the upper extremities and homolateral aplasia of II, III, IV, V finger. Attention is drawn to the importance of reporting diagnosed cases in order to further our knowledge of the syndrome. The Authors are looking with a big interest the correlation between hair treatment and Poland's anomaly. PMID- 1301487 TI - [Evaluation of the effectiveness of cisapride in the treatment of gastroesophageal reflux]. AB - To evaluate the effectiveness of administration of oral cisapride in patients with gastro-esophageal reflux, we studied 25 children, aged 1 month-7 years (mean 16.2 months) affected with GER. At the time of diagnosis and 8 weeks after treatment, patients were clinically evaluated and underwent a 24-hour continuous esophageal pH-monitoring. After treatment a complete regression of symptoms was observed in 20/25 patients. Moreover we recorded a significant reduction in the percentage of reflux time (p < 0.0001) and in the Jolley score (p < 0.0001), a very accurate scoring system to evaluate the pH-metric tracing, after treatment. It is concluded that cisapride is a useful agent both for the relief of symptoms and for the improvement of pH-metric parameters in children with GER disease. PMID- 1301488 TI - [The absence of a central lower incisor in a medieval subject from the Norman cemetery of San Lorenzo di Aversa (Caserta)]. AB - The authors describes a case of hypodontia in a male subject aged about 45 years and coming from the medieval necropolis of San Lorenzo of Aversa (Caserta, South Italy), dated to 890-1290 A.D. Hypodontia consists of the absence of a central inferior incisor (probably the left). Radiographic examination excluded the presence of a healed traumatic lesion. For this reason, the authors suggests that the described hypodontia was related to a primary agenesia of the central inferior incisor. PMID- 1301489 TI - [Psychometric and psychofunctional studies of a group of patients with craniomandibular disorders]. AB - The base myoelectric of masticatory muscles, and their response to stressor, was studied in a group of patients affected with craniomandibular disorders (CMD) and in a control group. Patients suffering from craniomandibular disorders were affected by at least two of these three groups of symptoms: 1) articular and/or muscular pain; 2) articular noise; 3) alteration of mandibular mobility. The psychofunctional investigation was as follows: in order to measure the base myoelectric activity of the masticatory muscles and their response to stress, the Myotron 222 two-channel electromyographs were used, so as to record the activity of four muscles contemporaneously. The research was conducted on the masseter and anterior fascia of the temporal muscles, which are the most readily accessible of the elevator muscles. A non-specific stressor (shot pistol) was administered to the subjects after the base myoelectric level had been established. These factors were evaluated on the electromyograms: base activity before the stressor; the shape of the response to the stressor; the recovery time after the stressor. The minimum activity before the stressor was usually measured as the minimum activity the subject was able to maintain for roughly one minute. The psychometric investigation used "Minnesota Multiphasic Personality Inventory" (MMPI); this is a nonprojective personality test widely used in clinical psychology. The base level of myoelectric activity was higher in patients affected with craniomandibular disorders than in healthy patients, who generally had low initial values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301490 TI - [A current update on the etiopathogenesis of palatoschisis]. AB - By means of a review of the most recent literature, the authors report on "state of the art" about etiology and pathogenesis of cleft palate. Epithelial mesenchymal interactions regulating growth and orientation of palatal shelves, as well as teratogenic effects on such ultrastructural development control by endogenous and exogenous substances, are described. PMID- 1301491 TI - [A clinical study of the efficacy and tolerance of nimesulide compared to flurbiprofen and sodium diclofenac in the prevention and treatment of postoperative pain and inflammatory symptoms in dentistry]. AB - The efficacy and tolerability of a new pharmaceutical formulation of a non steroid anti-inflammatory drug, nimesulide were studied in a double blind study in comparison with flurbiprofen and diclofenac sodium, in 150 patients suffering from postsurgical pain-inflammatory symptoms. The three drugs, administered in a dose of one suppository twice a day for 10 days, showed marked anti-inflammatory, analgesic and antipyretic activity and produced a significant, progressive improvement in the typical symptoms of the inflammatory state. Nimesulide evidenced the greatest speed and duration of therapeutic action. Assessment on the efficacy and tolerability as expressed separately by the physician and the patients were positive in almost all cases of the three treatments. PMID- 1301493 TI - [Schwannoma located in the tongue. A clinical case report]. AB - Schwannoma or neurilemmoma and neurofibroma are two tumors of the peripheral nerves originating in the nerve sheaths. Schwannoma account for just over 1% of benign tumors reported in the oral cavity. The tongue is unanimously considered the most frequent site at this level; however, the tip is the least affected part of the organ. The case of schwannoma reported here is the third observed with a lingual localization in 18 years by the Division of Maxillo-Facial Surgery of The Odontostomatological Clinic of the University of Turin. The case is of interest due the rarity of this pathology and the presence of non-significant symptoms for a presumed initial diagnosis. CASE REPORT. A 21-year-old woman was referred to our attention following the appearance two years earlier of a slowly growing swelling on the tip of the tongue. The patient complained of the fastidious presence, disturbance to mastication and phonation and occasional paresthesia of the tip of the tongue. The small mass, which was clearly evident on examination, was covered with normal mucosa. On palpation it had a hard-elastic consistency; it was slightly painful, smooth and partial mobile on surrounding levels. The patient underwent the surgical removal of the neoplasia under anesthesia. The mass was well capsulated and a good cleavage plane was easily found. The neoformation was yellowy grey, oval bean-shaped, measuring 1.9 x 1.3 x 1.1 cm. The histological diagnosis, confirmed by immunohistochemical tests, was benign Antoni's, type A schwannoma. The postoperative period was good an there was no recidivation during the course of a one-year follow-up. DISCUSSION AND CONCLUSIONS. Benign schwannoma, which are relatively rare in the oral cavity, represent a pathology which are often not taken into account during clinical practice. Symptoms which take the form of slight hypoesthesia and vague paresthesia may lead to the suspected diagnosis of this type of neoplasia. The final diagnosis is always made after a definitive histological examination. Differential diagnosis must be made in relation to malignant tumors (on the basis of anamnestic data relating to the speed of growth and clinical appearance of the neoplasia) and, above all, in relation to numerous benign neoformations based on epithelial and connective tissues (lipoma, fibroma, leiomyoma and adenoma). Treatment is always surgical: in the case reported here, the exeresis of the lesion also allowed its histological characterization (excisional biopsy). Surgery was conservative and did not require local or locoregional prophylactic measures. After the final histological diagnosis of schwannoma, the patient underwent a thorough general objective examination to check the presence of other characteristic signs of Von Recklinghausen's syndrome, have a probability of malignant degeneration ranging between 5 and 16%. Isolated schwannoma hardly ever become malignant and in general, if exeresis is complete, no recidivation occurs after surgery. PMID- 1301492 TI - [Roxithromycin in dental infections]. AB - Roxithromicin is a semisynthetic macrolide antibiotic, with similar antibacterial activity to erythromycin. It is characterized by an excellent pharmacokinetic profile and a good tissue penetration. Particularly at the dose of 300 mg per day the dental tissue diffusion is extremely good, and this is important to oppose the oral cavity infections. Oral cavity infections can be either odontogenic or non odontogenic. Odontogenic infections are typically primary and are caused by commensal bacteria (oral Streptococci, Bacteroides sp., Veillonella sp. and Fusobacterium sp.). The antibacterial spectrum of roxithromycin is very large and includes many of the most frequent strains responsible for oral cavity infections. A very interesting characteristic of roxithromycin is its penetration in macrophages (uptake) that allow a more rapid inhibition of bacterial activity. To evaluate the clinical efficacy and tolerance of roxithromycin in the treatment of odontogenic infections, an open study was performed. This study evaluated both the microbiological and clinical aspects. Thirty patients (21 females and 9 males) who had not been previously treated with antibiotic or antibacterial drugs, affected by infective dysodontiasis, gingivitis and periodontal diseases, received 300 mg per day (once a day) of roxithromycin for an average period of 6 days. The symptomatology considered was: intumescence, redness, pain, lymphangitis and presence of trismus. Clinical symptomatology was assessed at the start and at the end of the treatment. The symptomatological improvement due to roxithromycin was rapid and very effective. After 6 days of therapy, the improvement was statistically significant (p < 0.01) compared to basal conditions. No adverse reactions or side-effects were complained during the study. No changement were detected in laboratory parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301494 TI - Neutrophil dysfunction in prepubertal periodontitis associated with Papillon Lefevre syndrome. AB - Although prepubertal periodontitis (PP) is often associated with the Papillon Lefevre (PLS), the etiopathogenetic mechanism in this disease has not been clarified as yet. A three and half year old female with leukocyte chemotaxis deficiency and decrease of T-lymphocytes is presented. The immunohistochemical evaluation of neutrophils showed a reduction of myeloperoxidase content, whereas ultrastructural studies revealed no particular change. The possible role of such a deficiency in the pathogenesis of the periodontal lesion is discussed. PMID- 1301495 TI - [Keratoacanthoma of the lower lip. A review of the literature and clinical case report]. AB - The authors report a case of keratoacanthoma localized on the prolabium of the lower lip. They focus their attention on the difficulty of making a correct diagnosis and on the complexity of differential diagnosis with squamous cell carcinoma. After incisional biopsy of the lesion, treatment took the form of the complete excision of the neoplasm which is indispensable for a definitive diagnosis. The keratoacanthoma, although being an absolutely benign lesion, in fact requires complete exeresis in order to perform an histological examination of the entire neoplastic mass and thus definitively rule put the presence of squamous cell carcinoma. If correctly performed, the operation leaves very little scarring and satisfies the patient's esthetic and psychological expectations. PMID- 1301496 TI - [A case of osteoma of the mandible]. AB - Osteoma is a benign bone tumour with a very slow growth. In the maxillofacial district the paranasal sinuses and the mandible are more frequently involved. This type of tumour is clinically asymptomatic and the signs of its presence are due to the fact that its expansive and centrifugal growth changes the face features. The surgical operation has a double aim: to solve the aesthetic problem and to prevent complications. In fact, obstructions and compressions ab estrinseco may compromise the function of the nearest organs. The aim of our work has been to show a clinical case which is interesting from a clinical, diagnostic and therapeutic point of view. PMID- 1301497 TI - [Localization of the DNA segment coding for the synthesis of fraction I on the pYT plague pathogen plasmid]. AB - Fragmentation of the pYT plasmid of the plague pathogen by ten restriction endonucleases has been studied. The evidence has been obtained in support of the possible presence of the movable genetic element containing a HindIII site within the plasmid pYT. The gene encoding the I fraction of the plague pathogen has been cloned. The physical map of the pYT plasmid has been constructed with the use of restriction endonucleases BamHI, XhoI, BstEII, SmaI, EcoRI, and HindIII. The fragment of the plasmid DNA coding for the synthesis of the plague pathogen fraction I has been mapped. PMID- 1301498 TI - [Optimization of DNA blot hybridization conditions for various types of membranes]. AB - A set of experiments has been conducted to choose the optimal conditions for DNA transfer and fixation on two types of the nitrocellulose, three types of nylon membranes and on capron filters. The buffer capillary transfer systems, electroblotting and gel hybridization are analyzed. Two techniques for DNA binding have been tested under different transfer conditions for all the membrane types: a vacuum fixation at 80 degrees C and a UV-exposure. The results indicate the critical dependence of the efficiency of blot-hybridization on the conditions of UV-treatment. The UV-exposure longer or shorter than the optimal one resulted in a loss of the hybridization efficiency. The optimal DNA-transfer and fixation conditions are recommended for all the membranes tested. The dependence of the optimal transfer and binding conditions on the specific characteristics of different membrane types was demonstrated for maximal sensitivity of the blot hybridization. PMID- 1301499 TI - [Cloning and expression of the Arthrobacter globiformis fcb genes in Bacillus subtilis]. AB - The fcb genes of Arthrobacter globiformis KZT1 coding for the dehalogenase (4 chlorobenzoate-4-hydroxylase) activity have been cloned. The characteristics of fcb genes expression have been studied. The recombinant strains of Bacillus subtilis 6JM15 (pCBS 311) and 6JM15 (pCBS1) have shown the decreased level of substrate dehalogenation as compared with the one in the parent strain KZT1 and the recombinant strains of Escherichia coli and Pseudomonas putida. PMID- 1301500 TI - [Modification of Sau 6782 methylase: preparation, properties]. PMID- 1301501 TI - [Preparation of single-stranded E1A-oncogene DNA fragments from simian adenovirus SA7 by endonuclease hydrolysis recombinant phage M13 SS-DNA complexed with oligonucleotides, containing restriction sites]. AB - The ss-DNA of the (+) and (-) chains of Ela DNA fragment was obtained by hydrolysis of the recombinant bacteriophages M13 mp8G and mp9G (where G is 1-1750 bp:, E1a region of oncogene SA7) in complexes with the 16 bp oligonucleotides containing AluI and BspRI sites of restriction and sequences complementary to E1a SA7. The obtained fragments overlap the E1a zones associated with the immortalizing potential of SA7. PMID- 1301502 TI - [Genetic control of tetracycline resistance in bacteria]. AB - Modern data on prevalence, structural and functional organization of the tetracycline resistance determinants in bacteria are reviewed. The three mechanisms of the antibiotic resistance are the tetracycline efflux, the ribosomal protection and the antibiotic modification. The problems of evolution of tetracycline resistance genes are discussed. PMID- 1301503 TI - [Cloning and expression of the Clostridium thermocellum gene in cyanobacteria Anacystis nidulans R2 cells]. AB - The XhoI-SalGI fragment of the plasmid pCI DNA was inserted into the SalGI site of the cyanobacterium Anacystis nidulans R2 integrative vector plasmid pIAH4. The fragment incorporates the endoglucanase gene of Clostridium thermocellum cloned earlier within the 6.7 kb DNA sequence. The recombinant plasmid DNA was transformed into Anacystis nidulans R2 cells. The cloned endoglucanase gene was shown to express in the cyanobacterium cells. The enzyme synthesized is accumulated within the cytoplasm of Anacystis nidulans cells and is not secreted into the periplasm. PMID- 1301504 TI - [Ischemic cerebellar and brain stem lesions in CT findings]. AB - The author analysed CT studies of 117 patients with ischaemic lesions of the cerebellum and brainstem. The clinical appearance in these cases is often unspecific. This was confirmed by false clinical diagnosis in most patients. CT diagnosis is particularly difficult in cases with mass effect which was found in 24.8% of the patients. Follow-up CT studies can help in proper diagnosis. The territory of the superior cerebellar artery was most frequently involved in the cerebellum, while the territory of the paramedian perforating in the brainstem. In 26.5% of the patients ischaemic lesions of the cerebellum and/or brainstem were bilateral, in 39.3% were accompanied by cerebral infarcts. It can be concluded that they are the component of general vascular insufficiency of the whole bain. PMID- 1301505 TI - [Botulin in the treatment of local dystonia]. AB - Botulin A has been introduced for the treatment of local dystonia especially blepharospasm and torticollis. Three cases of blepharospasm and 5 cases of torticollis were treated with botulin injections directly into the muscles by a method presented in detail. Good effects were obtained in blepharospasm but very poor in torticollis, which may have been due to too low doses of the toxin and inadequate choice of injection points. The method is safe and in only 1 case transient weakness of the masseters was noted. PMID- 1301506 TI - [Early signs of cognition disorders in children with subacute sclerosing panencephalitis in initial stage]. AB - The purpose of the study was to find some characteristic features of cortical defects in the neuropsychological examination of children with SSPE. These findings could be very useful in early differential diagnosis. We analysed the results of the neuropsychological assessment of 13 children selected from a group of 100 patients. The most frequent defects were found in the visuo-spatial functions. The clinical analysis of the obtained results was studied in view to establish, whether there are the signs of the dysfunction of the right or both cerebral hemispheres. PMID- 1301507 TI - [The usefulness of clinical signs and selected diagnostic methods in the diagnosis of tuberous sclerosis in children]. AB - 55 children took part in the study. Besides depigmented naevi and epilepsy, echocardiography plays the most significant role in the diagnosis of tuberous sclerosis in children below 2 years of age. In older children, besides dermatologic examination, cranial computerized tomography and abdominal ultrasonography are the most effective methods. This study suggests that the diagnostic effectiveness of different clinical signs and examinations depends on the age of the examined children. An appropriate diagnostic procedure may lead to earlier diagnostic and allows to avoid excessive examinations. PMID- 1301508 TI - [Expression of surface antigens on lymphocytes stimulated by non- specific mitogens in multiple sclerosis patients]. AB - In studies performed on 30 MS cases, as compared to 16 healthy individuals, significantly higher expression of HLA class II antigens, interleukin 2 receptor and antigens specific for lymphocytes B was observed. In MS patients after stimulation by non specific mitogens increased expression of HLA class II antigens and increased proliferation induced by PMA was found. The obtained results suggest absence of any greater modulation of surface antigens on the lymphocytes stimulated by non-specific mitogens. Our observations indicate that the number of activated T cells, as assessed by expression of Il-2 receptor, is in MS patients relatively low. PMID- 1301509 TI - [Ultrastructural studies of cells in peripheral blood and cerebrospinal in meningococcal cerebrospinal meningitis]. AB - Cells of peripheral blood and cerebrospinal fluid were studied in cases of meningococcal meningitis, and in peripheral blood of healthy controls. In the acute phase of the disease the neutrophils in cerebrospinal fluid showed evidence of phagocytosis activation with presence, among other signs, of numerous cytoplasmic processes. Stages of degeneration of these cells were observed with cytoplasm bulging into the nucleus, strong concentration of nuclear chromatin. In the light of a comparative assessment of cellular structures it was found that the population of neutrophils in peripheral blood is a more stable population showing no morphotic evidence of degeneration. In cerebrospinal fluid eosinophils three types of specific granules were found evidencing hydrolysis stimulation in these cells. In the acute phase of the disease the monocytes in the cerebrospinal fluid showed evidence of transformation, and during convalescence signs of degeneration appeared. Lymphocytes rarely found in the cerebrospinal fluid had features of metabolic stimulation (increased number of mitochondria, lysosomes and pinocytic vacuoles). PMID- 1301510 TI - [Traumatic lesions of lower cervical spine]. AB - In the years 1965-1990 in the hospital department for treatment of spinal injuries 1330 patients with spinal lesions at the C5-Th1 levels were treated after admission early after trauma. The most frequent causes of injuries of this part of the spine were falls from horsecarts, jumping into water head first and traffic accidents. The relationship was analysed between the degree of spinal cord injury and the mechanism of spine injury, and also the results were compared of conservative and surgical treatment. The most severe damage to the spinal cord was observed after traumas involving the flexion mechanism. Typical crush fractures of vertebral bodies had be best prognosis. Significant neurological improvement was obtained in over 50% of the treated patients, and it was more pronounced and occurred more frequently after surgical treatment. PMID- 1301511 TI - [Surgical treatment of brain metastases from non-microcellular lung cancer]. AB - A retrospective analysis is reported of 185 patients treated at the Memorial Sloan-Kettering Cancer Center, New York, in whom in the period 1984-1989 metastases to the brain from non-microcellular lung cancer were removed surgically. The statistical analysis was done by the Kaplan-Meier test. For neurosurgical treatment patients should be qualified without metastases to other organs and with brain metastatic tumor accessible for operation. The median survival was 12 months after operation on the brain, and 27 months after thoracic operation. The patients with cerebellar metastases had the same survival time after the operation as those with supratentorial metastases. Radiotherapy had no influence on the length of survival after tumor removal. Recurrence of brain tumour occurred in half the cases. Reoperation in case of recurrence prolonged the survival by another 10 months. PMID- 1301512 TI - [Astrocytomas of the cerebellum in children: treatment and results]. AB - Between 1980 and 1987, 113 children with astrocytoma of the cerebellum were treated. The range of the age was 11 months to 15 years. 103 children were treated by surgery only and 10 received surgery and postoperative irradiation. Shunting was necessary in 22% patient with cerebellar astrocytoma. One-year survival for patients with cerebellar astrocytoma was 97%, five-year 89%. PMID- 1301513 TI - [Immunology of the central nervous system and brain tumors]. AB - Treatment of brain tumours, especially poorly differentiated gliomas, by conventional methods is usually unsuccessful. A possibility of improvement of these results could be given by mobilization of immune system mechanisms. This has been made possible by partial insight into the mechanism of this system, its specific relations with the central nervous system, and interaction between the tumor and the immune system. The aim of the paper was a surgery of the state of knowledge concerning the immunobiology of brain tumours. PMID- 1301514 TI - [Epilepsy and tremor in the XXY syndrome]. AB - Extrapyramidal tremor and epilepsy uncommon in Klinefelter syndrome were found in a 30 year old patient. CT scans revealed partially empty sella and subcortical cerebral atrophy. Chromosomal studies showed the karyotype 47, XXY. PMID- 1301515 TI - [Contribution to the clinical polymorphism in Huntington's disease]. AB - A family is described in which closely consanguineous parents had Huntington chorea and in their son a severe hypertonic-hypokinetic syndrome with pellagra like cutaneous changes was present. In two generations of the family in 6 subjects involuntary movements and gait disorders were reported. PMID- 1301516 TI - [Severe case of basilar migraine treated with flunarizine]. AB - In a man aged 40 years frequent attacks of basilar migraine with consciousness disturbances and signs of central nervous system defects developed due to circulatory failure in the posterior cerebral arteries and cerebellar arteries. The frequency and intensity of migraine attacks decreased only after treatment with flunarizine. PMID- 1301517 TI - [Transient global amnesia. Case report]. AB - All memory disturbances, especially those developing suddenly, cause anxiety of the patient. Transient global amnesia is a form of amnesia of interest in many aspects. The amnesia was described in 1964 by Fisher and Adams, and as yet about 1000 cases have been reported. Middle aged or elderly patients prevail. The attack of amnesia lasts from several to about 20 hours and begins suddenly being regarded as mental confusion. The amnesia covers recent and remote events in many years. During the attack the patient is not appearing to be ill, but is depressed not knowing what has happened. The awareness of own personality, the ability to solve logical problems and visuospatial functions are preserved. The ability to execute complex activities, e.g. car driving, is normal. The aetiology of the disorder is completely unknown. The hypotheses for explaining the syndrome are: 1. ischaemia in the posterior cerebral arteries region with transient fall of blood supply through the vertebrobasilar system, 2. epilepsy or migraine, 3. disturbed aggregation of platelets in the cerebral vessels leading to loss of vessel patency. The first hypothesis seems least plausible. Attacks of this amnesia were noted after triazolam, after thalamic infarction and cerebral angiography, in brain tumours, hydrocephalus, scleroderma, frontal lobe haemorrhage. After an attack the events occurring in it are not remembered. Recurrence of attacks is very rare. Most authors consider that the disorder is benign and regresses without sequelae or only with slight changes in cognitive functions and memory fixation. PMID- 1301518 TI - [A case of aneurysmal bone cyst of orbit roof in a boy aged 14]. AB - A case of a very rare localisation of aneurysmal bone cyst within orbital roof is presented. The peculiar site of the pathological process caused two-way expansion, i.e. towards the orbit and the cranial cavity. The patient was operated on using the transcranial approach and total cure was obtained. PMID- 1301519 TI - [Coexistence of colloid cyst of the third ventricle with pituitary dwarfism in a female aged 16]. AB - A 16-year-old patient with pituitary dwarfism is reported, in whom a colloid cyst was found in the III ventricle. The authors believe that pituitary disorder and colloid cyst were a result of developmental anomalies manifesting themselves at various times. PMID- 1301520 TI - [Dissecting aneurysm of the posterior inferior cerebellar artery]. AB - A 23 year old woman with dissecting aneurysm of the left posterior inferior cerebellar artery located distal to the branch feeding medulla oblongata is described. Trapping of the aneurysm with the aid of 2 clips was without any influence on neurological state of the patient and prevented recurrent hemorrhage. PMID- 1301521 TI - AIDS update. PMID- 1301522 TI - Implementing the framework directive. AB - The Management of Health and Safety Regulations will be operative from the beginning of 1993. While duties for employers are similar to those laid out by previous legislation, Gillian Howard suggests that aspects of the new Regulations will see a new role for occupational health practitioners. PMID- 1301523 TI - Keeping up standards. PMID- 1301524 TI - Industrial audiometry. AB - Hearing surveillance is a mandatory requirement of new EC Regulations. Dr Stephen Karmy believes that audiometry has an important part to play in a company's hearing protection policy and aids compliance with new legislation. PMID- 1301525 TI - Facing up to acne. AB - Acne is generally considered to be a trivial condition, confined to adolescents, who are expected to 'grow out' of it by the time they become part of the working population. Dr Andrew Finlay's experience suggests otherwise and argues that acne can affect older sufferers and disable employees who are not referred for appropriate treatment. PMID- 1301526 TI - Substance abuse. Taking the lead in workplace policies. AB - The number of companies with alcohol policies is rapidly increasing. This trend has been largely led by health and safety departments in safety-sensitive industries. Helen Kogan believes that the time is now right for OH professionals to re-examine their involvement and take the lead in introducing preventive health care strategies in the workplace. PMID- 1301527 TI - EC legislation: shaping the future. PMID- 1301528 TI - Moving to a community based curriculum. AB - The move to a community based curriculum will play an important part in shaping the future of the profession. ANN LOWIS (left), director of nursing at The Robert Gordon University, believes that it will do much to develop professional credibility and recognition. PMID- 1301529 TI - NVQs: where are they leading. AB - Proposed changes in training and development means that it is time to stand up and be counted, writes SOHN chair, JEAN RAPER. She examines the work, to date, on National Vocational Qualifications and asks what affect they might have on the future of occupational health nursing. PMID- 1301530 TI - The wind of change in our profession. PMID- 1301532 TI - That was the year that was. PMID- 1301531 TI - Cardiovascular care: health matters in the workplace. PMID- 1301533 TI - [Selected problems in the evolution of scientific examination of the lymphatic system of the larynx and the surrounding region presented for clinical purposes]. AB - The most important results of the morphological research of the lymphatic system of the larynx with surrounding tissues were presented. Based on section specimens of larynx the topography of the lymphatic system was described. We also described changes in the lymphatic system after radiation and after manifestation of squamous cell carcinoma in this region. We concluded that the main causes of our clinical adversities in treatment of larynx cancer were lymphatic stasis, cancer embolism of small nodes between mucosa and deep lymph nodes of the neck. We also studied over the methods of intravital examinations of the neck's lymphatic system. PMID- 1301534 TI - [Microlaryngoscopy and microsurgery in diagnosis and treatment of laryngopathies]. AB - In the Otolaryngology Clinic of the Medical Academy in Lublin in the 21 year period (1971-1991) there were performed 2488 microsurgical operations of the larynx. The authors analyse their own clinical material paying particular attention to relative precancer states, early diagnosis of laryngeal cancer and an increase of the number of preinvasive cancer (cancer in situ) diagnoses. The authors postulate that indications for clinical diagnostic and therapeutic procedures should be considerably extended in diseases of the larynx. There should be used an operating microscope which will considerably shorten hospitalization period of patients and significantly contribute to an increase of the percentage of early diagnoses of cancer of the larynx. PMID- 1301535 TI - [Correlation of clinical and histological pictures of precancerous conditions and early-stage glottic carcinoma]. AB - 310 patients were analysed with different pathological changes in the larynx, which are classified as premalignant stages and 114 cases with early cancer of the vocal cords. Out of the 310 cases, 230 cases were with chronic hypertrophic laryngitis, 44 cases with hyperkeratotic papilloma and 36 with juvenile papilloma in adults. Histologic verification of the bioptic and operative material was performed in a series of examinations. This showed that leukoplakia and one-sided pathological changes of the larynx are clinically characteristic for carcinogenesis. In chronic hypertrophy with leukoplakia, cell dysplasia occurred in 12.2% and atypia occurred in 9.8%. Hyperkeratotic papilloma underwent malignant transformation in 70.5% cases. Among the juvenile papilloma in adults with frequent recurrence of the disease, leukoplakia and dysplasia occurred periodically. Idiopathic malignant transformation of juvenile papilloma happened in only one patient. Adequate treatment of the premalignant stages effectively prevents further growth of cancer in 97% of the cases. Surgical treatment of cancer of the glottis in T1N0 and T2N0 gave a 5-year and longer survival period in 82.8%. There results were better than after radiotherapy of about 15%. PMID- 1301537 TI - [Ultrasonography in the diagnosis of larynx carcinoma]. AB - The aim of our work was the application of sonographic method in the diagnosis 75 patients of larynx carcinoma. Aloka Hellige type SSD 280 LS was used on the examination in real time. The sonographic images were compared with the results obtained in the indirect and direct laryngoscopy, postoperational evaluation and histopathological picture. Sonography may prove to be a potentially useful for expanse of cancer of the larynx. PMID- 1301536 TI - [Functional results after supracricoid reconstructive laryngectomy with cricohyoidopexy (chp) and cricohyoidoepiglottopexy (chep)]. AB - The functional results in 61 patients after supracricoid reconstructive laryngectomy with CHP (28 cases) and CHEP (33 cases) performed in the University ENT Department in Szczecin between 1971-1989 are presented. Satisfactory lower airway protection in about 93% and respiration in the natural way in 83% are obtained. It was impossible to decaniulate 11 patients. The voice was socially sufficient in 89%. PMID- 1301538 TI - [On primarily bifocal laryngeal carcinoma and bronchogenic cyst of the neck]. AB - The authors discuss a problem of rarely occurring bifocal carcinomas with the presentation of their own case of laryngeal carcinoma and branchiogenic cyst of the neck. They pay attention to histopathologic features underlying the diagnosis of branchiogenic cyst carcinoma and to the necessity of oncologic alertness in tumors of these kinds. PMID- 1301539 TI - [Indications and contraindications for tympanoplasty, critical opinion upon this operations]. AB - Indications and contraindications for tympanoplasty and critical opinion upon results of this operations were presented. Attention has been brought to the role of hearing aids in restoration of social useful hearing in patients after tympanoplasty. PMID- 1301540 TI - [Surgical treatment longstanding, irreversible, peripheral facial palsy]. AB - Authors described the technique of surgical treatment of the longstanding, irreversible peripheral facial palsy. Both neurography and myoplasty were combined. The most functionally effective detail in this method is the substitution of the hypoglossal nerve function with the descending branch of the cervical ansa. PMID- 1301541 TI - Early and middle latency auditory evoked responses in audiology and neurootology. PMID- 1301542 TI - [Caloric vestibular tests in normal subjects with increasing age]. PMID- 1301543 TI - Hearing preservation in acoustic neurinoma surgery. AB - The chances of hearing conservation in patients with acoustic neurinoma increases by early diagnosis of small tumors. An early diagnosis of an acoustic neurinoma is achieved through the application of a minimal diagnostic test battery to evaluate unilateral otological complaints such as tinnitus, sensorineural hearing loss and balance disturbances. This minimal evaluation comprises puretone audiometry and ABR. Patients showing abnormal findings should be pursued with imaging evaluation such as MRI with gadolinium contrast. The choice of surgical approach for removal of an acoustic neurinoma (transtemporal, translabyrinthine or suboccipital) will depend on the size of the tumor and the patients' hearing. The possibilities should be discussed with the patients. Postponing the surgical intervention due to the possibility of facial paralysis or loss of hearing is difficult to rationalise. During the last 15 years, the development in diagnostic and surgical techniques has made it possible to conserve hearing during surgery at least in some patients suffering from acoustic neurinoma. Early diagnosis of small tumors increases the chances to conserve hearing. Therefore, all nonspecific early otologic symptoms should be thoroughly evaluated to exclude the presence of an acoustic neurinoma. Acoustic neurinomas usually arise within the internal auditory meatus and grow further into the posterior cranial fossa. The first symptoms usually are hearing loss, tinnitus and balance disturbance. These symptoms can occur in combination or individually. Accordingly, all cases presenting with one or all of these symptoms in the absence of an obvious etiology, such as posttraumatic hearing loss, require the exclusion of an acoustic neurinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301544 TI - [Reinke's edema and thyroid hypofunction]. AB - The authors carried out a study of thyroid function determining the levels of thyroxine (T4) and triiodothyronine (T3) in the serum of 60 patients (33 men, 27 women) between 31-79 years with Reinke's edema who had been treated microsurgically and phoniatrically. Hypothyroidism was found in one patient (a teacher, 47 years old, smoker). The study suggests that hypothyroidism is not an aetiological factor in the development Reinke's edema, which is in accordance with what other authors report. PMID- 1301546 TI - [Laryngeal dyspnea due to Arnold-Chiari syndrome]. PMID- 1301545 TI - [Qualitative determination of chemical compounds in the tissue of laryngeal cancer by x-ray microanalysis]. AB - The authors presented the results of chemical compounds in the laryngeal cancer tissue in 20 patients with clinically and histologically confirmed plano epithelial carcinoma using own modification of x-ray microanalysis method. Comparison between the healthy and neoplasmatic tissue showed as follows: 1) both healthy and neoplasmatic tissue showed the presence of Cd, Zn, Fe, Mn, Mg and Si, P, S, Cl, K, Ca, Ti; 2) the neoplasmatic tissue showed the presence of Pb whereas it was not observed in the healthy tissue; 3) both Pb and Cl were irregularly concentrated in the neoplasmatic tissue while in the healthy tissue showed regular concentration. The authors discuss some methodological aspects and try to interpret the obtained data in the view of toxic, mutagenous and carcinogenous role of the Pb. PMID- 1301547 TI - [On the bacteriostatic or bactericidal function of ceruminous glands secretion]. AB - The authors present the results of their research concerning the bacteriostatic or bactericidal function of the secretion of ceruminous glands of the external auditory duct. In accordance with the statements of the other authors, neither bacteriostatic nor bactericidal function of the ear wax was discovered. PMID- 1301548 TI - [A simple method of the vocal cord laterofixation]. AB - Six patients were treated by the new method of vocal cord latero-fixation which was the combination of the extra-laryngeal and intra-laryngeal approach. The functional contraindication for this procedure is the anatomic configuration of larynx. PMID- 1301549 TI - [Septal fascioplasty as the method of surgical treatment of nose bleeding in patients with Rendu-Osler-Weber disease]. AB - The authors describe an own method of surgical treatment of nosebleed caused by Rendu-Osler-Weber's disease. For closure of nasal septal defects we used free graft of fascia lata. In five patients treated by our method, the transplantation ended successful; during the several weeks after operations the fascia lata was covered with epithelium growing from the surrounding tissues. Control examinations did not demonstrate recurrences. In two patients our method was unsuccessful. PMID- 1301550 TI - [Difficulties in diagnosis of rhinitis in children treated at the Otorhingologic outpatient department of children's hospital in Bialystok]. AB - The aim of this study was an analysis of rhinitis etiology in 105 children treated in Otorhinolaryngology Outpatients Department, Children Clinical Hospital in Bialystok. In 58 patients seasonal allergic rhinitis, stimulated by grass antigens, in 37 patients infectious rhinitis and in 10 patients perennial allergic rhinitis stimulated by mites was recognised. The diagnosis in this last group was made using laryngological investigations skin "prick tests" and specific IgE level against mites. PMID- 1301551 TI - [Ossicular reconstruction of the loss of the superstructure of the stapes]. AB - At 43 patients the full or almost full reconstruction of the sound conductive system of the middle ear has been performed. The colemella from autogenous cartilage was positioned on the footplate of the stapes or the mallens was rotated on the footplate. In the 4 years after operation the negative functional results were found. The applied operations techniques have been criticised. PMID- 1301552 TI - [The efficiency of vestibular organs in persons addicted to opioids, barbiturates and volatile organic substances examined during the period of abstinence]. AB - Opioids, barbiturates and volatile organic substances are the most common drugs used in Poland by addicts. In the literature there are no data concerning efficiency of vestibular organs of addicted persons examined during abstinence period. 74 drug addicts and 50 healthy persons were subjected to ENG examinations (spontaneous nystagmus, positional ny gaze ny, eye-tracking test, optokinetic test, rotatory test and caloric test were evaluated). ENG showed abnormal records in all tests performed in the addicted persons. This study has revealed that addicts have insufficiency of vestibular organs, which is probably a result of central lesions. PMID- 1301553 TI - [Syndromes related to altered structures and function of the respiratory cilia]. PMID- 1301554 TI - [History of electrophysiological investigations of organs of hearing]. AB - Development of electrophysiological examinations of organ of hearing was examined, starting from Luigi Galvani's discovery of electrical activity of biological tissue, through experimental research aiming at localization of cortical hearing centres. The studies by Wever and Bray, as well as, Ruben's team of Baltimore underline the significance of potentials expressing electrical activity of cochlea and acoustic nerve fibres. Pioneer studies of Hallowel Davis (called "father of ERA studies"--Electric Response Audiometry) and his first wife, Paulina. Several other studies done by his research team were mentioned. Besing on these papers and papers of some other authors, a short description of slow cortical potentials and cochlea potentials was done as they were discovered and introduced to clinical tests. The discussion covered also investigations of Sohmer and Feinmesser, as well, as, those of Jewett and Willistone on systematization of structures generating waves in auditory brain stem responses. The paper is concluded with the description of the recent classification of auditory potentials induced by an acoustic stimulus. The discussion on the development and progress of electrophysiological studies of the organ of hearing is concluded with some remarks on otoacoustic cochlea emission discovered by David Kemp of London in 1978. PMID- 1301555 TI - [The picture of Polish practicing otolaryngologist at the turn of the 19th century]. AB - The life, scientific, professional and organizational achievements are presented of Wladyslaw Wroblewski (1860-1906), a distinguished Polish otolaryngologist, head of the out-patients department of Protestant Hospital in Warsaw with a wide experiences with the educational medical institutions abroad (especially at A. Politzer in Vienna). Dr. Wrolewski was a well-known Varsovian physician living in the second half of the 19th and the beginning of the 20th century in Warsaw. He was a author of numerous scientific publications. His achievements in rynology and laryngology are presented in more details, particularly those surgical treatment of larynx tuberculosis, the neoplasms of upper respiratory tract, surgical treatment of tonsils. The author discussed his view on certain nose, pharynx and larynx diseases, their diagnosis and therapy. Dr. Wroblewski was a co editor of the Polish medical periodical "Gazeta Lekarska"; he was also a good teacher of a great number of distinguished laryngologists. The personality traits of this appreciated man were also depicted. PMID- 1301556 TI - [Chronic granulomatous otitis media with irregular symptoms]. AB - In the ENT Department, Medical Academy of Cracow, the patient with tinnitus synchronized with pulse as a first symptom of chronic granulomatous otitis media was treated. The diagnosis was made on the basis of the CT examination. The tympanoplasty was successfully performed. PMID- 1301557 TI - [ Epistaxis as a first symptom of hypernephroma]. PMID- 1301558 TI - [Metastasis of the cancer of mamma in the middle ear]. AB - The rare case of the metastasis cancer of mamma on the middle ear was described. The diagnostic difficulties, treatment and clinical course were also discussed. PMID- 1301559 TI - [A case of congenital middle ear abnormalities of Siebenmann's type]. AB - There is presented a case of congenital anomalies of the middle ear. TORP (Richards) prosthesis successfully substituted for the aplastic chain of auditory ossicles and made it possible that hearing returned to the norm. PMID- 1301560 TI - Nursing care of a patient with hip replacement surgery--a case study. PMID- 1301561 TI - Quality assurance tool in operation theatre. PMID- 1301562 TI - Refresher course on management skills in nursing. IX. PMID- 1301563 TI - Distance education for nursing personnel. PMID- 1301564 TI - Ethical concerns about noncompliance in the chronically ill patient. AB - This article is a discussion of the research trends concerning noncompliance, ethical concerns about noncompliance with prescribed treatment of chronic disease, requirements for ethical practice concerning noncompliance and chronic illness, and needed research about the relationship between noncompliance and coping with chronic disease. Questions are proposed to guide specific research concerning the ethics and therapeutic regimen compliance of patients with chronic cardiac disease. PMID- 1301565 TI - Nursing management and rehabilitation of chronic ventricular assist device (VAD) patients. AB - With the increasing number of heart transplants performed annually and the number of available organs decreasing, more patients are being bridged to transplant by mechanical circulatory support (MCS) systems during their wait for a donor organ. The duration of assistance with MCS has also increased due to this shortage of donor organs. The Artificial Heart Program at the University of Pittsburgh, recognizing this changing population, has shifted the focus of care from acute support to chronic support of VAD patients. Providing care directed at long-term support has promoted rehabilitation and helped to improve the overall bridge experience. At the University of Pittsburgh, 34 patients were implanted with MCS devices as a bridge to transplant between June 1987 and September 1992 (Figure 1). Thirteen of these patients were supported for over 60 days. Of these, three were eventually discharged to an out-of-hospital facility six blocks from the medical center. Eleven of the 13 patients supported over 60 days were discharged following successful orthotopic cardiac transplantation. In response to this increasing duration of support in the bridge to transplant patient, the role of the nurse has changed significantly. Nursing care initially focused on acute physiologic monitoring procedures that are restricted to an intensive care setting. Today the role of the MCS nurse encompasses a much broader area including medical care, education, and patient rehabilitation. It is important to realize that these aspects of care begin when a patient is identified as a MCS candidate and continue throughout the acute postoperative phase into the chronic phase of recovery. PMID- 1301566 TI - Heart rate variability in cardiac disease. PMID- 1301567 TI - Diagnostic uses of epicardial electrodes after cardiac surgery. AB - Dysrhythmias after cardiac surgery are common. The etiologies and treatments are diverse depending upon the origin of the dysrhythmia. An atrial electrogram obtained from epicardial electrodes temporarily positioned at the time of surgery can detect the origin of an anomalous rhythm. This article discusses the diagnostic use of epicardial atrial electrograms after cardiac surgery, types of atrial electrograms, steps to interpretation, and nursing implications. An understanding of their use can facilitate patient management and therapy. PMID- 1301568 TI - Comparison of psychologic stress responses in patients and spouses ten weeks after a cardiac illness event. AB - A stress scale that is brief and easy to administer would be clinically useful to assess patients' and spouses' psychological stress responses to a cardiac illness situation and provide objective data for health care recommendations. The purpose of this study was to: a) develop and test an instrument to evaluate the stress or difficulties associated with the recovery process after a cardiac event; and b) assess the similarities and differences between patients' and spouses' perceptions of stress. Stress was conceptualized to be reflected by two broad dimensions, namely environmental stress and individual stress. A correlational survey design was used to examine patients' (n = 180) and spouses' (n = 168) stress responses 10 weeks after the cardiac event. The findings suggested that the tool demonstrated satisfactory reliability and validity in measuring the patients' but to a lesser extent the spouses' stress responses. The three most significant stresses reported by most patients were uncertainty about if and when the illness might recur, not being able to participate in work or retirement activities, and adopting a low cholesterol diet. For the majority of spouses, the three most significant stresses were uncertainty about the husband's illness, increased demands within the marital relationship, and assuming more family roles. For those individuals trying to quit smoking or who quit immediately prior to the cardiac event, smoking was the most stressful change for patients and the second most stressful for spouses. Educational programs for cardiac patients and spouses need to provide information related to these stresses to offset the potentially adverse impact of stress and promote adjustment. PMID- 1301569 TI - The natural history and the prognosis of treated superficial bladder cancer. EORTC GU Group. PMID- 1301570 TI - Mechanisms of action of BCG in superficial bladder cancer. PMID- 1301571 TI - Upfront chemotherapy in invasive bladder cancer. PMID- 1301572 TI - Post cystectomy adjuvant chemotherapy: a clinical routine? PMID- 1301573 TI - Preservation of urinary continence and potency after cystoprostatectomy. AB - Between 1980-1989 a total of 349 patients underwent one-stage radical cystoprostatectomy and an orthotopic bladder substitution. 278 patients underwent the Camey I bladder replacement and in 71 patients a detubularized ileal loop was utilized (Camey II). 75 patients underwent a potency-sparing cystectomy (32 patients of the Camey I and 43 patients of the Camey II groups). All patients were followed at least one year and had continence and potency assessment. Among the patients who underwent the Camey I procedure, 66% achieved daytime continence and 21% night-time continence 6 months after surgery. One year after surgery 86% of patients had normal continence during the day and 47% was continent during the night. 14% of patients had episodes of day-time incontinence one year after surgery. Among the patients who underwent the Camey II bladder replacement 86% achieved day-time continence and 59% night-time continence 6 months after surgery. At one year after surgery 91% was continent during the day, 72% was dry during the night and only 9% had episodes of diurnal incontinence. Potency was achieved in 24 of 32 patients (75%) with the Camey I bladder substitution, and in 34 of the 43 patients (79%) with the Camey II bladder substitution. Our data demonstrate that excellent rates of continence and potency are achievable in the post-cystectomy population. Patients with the Camey II bladder replacement achieve continence earlier than patients with the Camey I bladder substitution. Diurnal continence is slightly better after the Camey II procedure, one year after surgery, but the difference is not statistically significant. Nocturnal continence is significantly better with the Camey II bladder substitution. PMID- 1301574 TI - The case for conservative surgery for renal cell carcinoma (RCC). PMID- 1301575 TI - Justifiability of conservative surgery for transitional cell carcinoma of the upper urinary tract. PMID- 1301576 TI - Lymph node metastases in renal cell carcinoma. PMID- 1301577 TI - Radical nephrectomy with and without lymph node dissection: preliminary results of EORTC Protocol 30881. The EORTC Genitourinary Group. PMID- 1301579 TI - Limitations of surgical curability in renal cell carcinoma. PMID- 1301578 TI - Role of lymphadenectomy in renal cell carcinoma. AB - A retrospective analysis of 97 consecutive patients with renal cell carcinoma, observed between 1983 and 1989, was performed. All patients underwent radical nephrectomy followed by extensive retroperitoneal lymphadenectomy which included hilar, laterocaval/lateroaortic, and interaortocaval lymph node dissection. Lymph nodes and distant metastasis accounted for 6.2% and 7.2% of the cases respectively. A statistically significant correlation between the stage and the grade of the tumor and the frequency of lymph nodes (p < 0.01) and distant metastases (p < 0.05) was found. In patients with no lymph nodes or distant metastases, the 5-year survival rate was 100%, 79%, 68%, and 50% for stage T1, T2, T3, and T4 respectively. No statistical difference in survival between stage T1, T2, and T3 was found. The size and histological grade of the tumor significantly affected the survival rate at 5 years. In fact, < 5 cm, 5-10 cm, and > 10 cm tumors had 93%, 52%, and 65% survival rates respectively, while G1, G2, and G3 tumors had 75%, 68%, and 21% survival rates respectively. In patients with nodal metastases and distant metastases the 5-year survival rate was 25% and 0%. Survival appears to be significantly influenced by the presence of lymph node and distant metastases, while retroperitoneal lymphadenectomy does not improve the survival of patients with lymph node metastases. PMID- 1301580 TI - Patterns of ploidy in renal cell carcinoma. AB - In a prospective study the patterns of ploidy in 119 kidneys from patients with renal cell carcinoma were analyzed by flow cytometry. A rate of DNA aneuploidy of 53% was observed in the investigated tumors. However, in 4% of the kidneys aneuploid cell distributions were also proven in macroscopically intact tissue far away from the tumor. Although we do not know at present, if these were benign, premalignant or malignant cell alterations, this observation should be considered for decisions regarding conservative renal surgery. PMID- 1301581 TI - Bladder cancer recurrence and its association with cytochrome P-450IID6 activity. PMID- 1301582 TI - Flow cytometric analysis and motility response to laminin and fibronectin of four new metastatic variants of the human renal cell carcinoma line RC43. AB - Using subrenal capsule implantation (SRC) in nude mice we have isolated 4 new sublines (RC43MSP, MBO, MLI, MDI) from the human renal cell carcinoma line (HRCC) RC43. These sublines exhibit an enhanced metastatic ability and a faster doubling time after subcutaneous (SC) transplantation in vivo, when compared to the parental line. With the aim of a better characterization of these new sublines we have performed a flow cytometric analysis (FA) of the DNA content and studied the motility response (MR) to laminin and fibronectin. FA results. The RC43 parental line showed a tetraploid pattern (DNA index: 2.08). Also the variant lines RC43MLI and RC43MDI were tetraploid (DNAind: 2.05 and 2.07, respectively). With RC43MDI a second peak in the tetraploid range was evident. The RC43MSP and the RC43MBO sublines both showed a hypertetraploid pattern (DNAind respectively 2.21 and 2.11). MR results. Motility studies showed that all RC43 lines, including the parental line, were stimulated to migrate in response to either laminin or fibronectin both from rat and human sources. There were no significant differences between the parental line and its variants in this respect, however. We conclude that by the use of FA at least two of the sublines (MSP and MBO) can be distinguished from the parental RC43 cell line, suggesting a different clonal origin of the various sublines. As all sublines, as well as the parental line, showed a large but similar response to migration-stimulating agents (such as laminin and fibronectin) determination of MR could not be used to obtain a further discrimination between the different sublines. PMID- 1301583 TI - Treatment of disseminated renal cell cancer with combinations of interleukin-2, lymphokine-activated killer cells, and alpha-interferon. PMID- 1301584 TI - Objective response of superficial bladder tumors to intravesical treatment (including review of response of marker lesions). PMID- 1301585 TI - The place of intravesical chemotherapy as defined by results of prospective randomized studies (substances and treatment schemes). PMID- 1301586 TI - BCG versus cytotoxic chemotherapy in the treatment of superficial bladder tumors. PMID- 1301587 TI - BCG-RIVM versus BCG-Tice versus mitomycin-C in superficial bladder cancer. Rationale, design, and interim analysis of the trial of the South-East Cooperative Urological Group, The Netherlands. PMID- 1301588 TI - BCG treatment in Tis of the urinary bladder, results of the EORTC Protocol 30861. EORTC GU Group. PMID- 1301589 TI - Impaired immune response by isoniazid treatment during intravesical BCG administration in the guinea pig. AB - At present, isoniazid (INH) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer, although it is not clear whether or not this reduces the antitumor efficacy of BCG. In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs. INH was given during 3 days starting on the day prior to the BCG administration. It was found that the administration of INH severely impaired the immunological effects of BCG. The induction of mononuclear cell infiltration in the bladder wall was reduced. Enlargement of the regional lymph nodes (weight and number of cells), and increase of Major Histocompatibility Complex (MHC) class II expression on the lymph node cells, normally observed after intravesical BCG administration, were inhibited by INH. Systemic immunity, measured by the DTH reaction in the skin to PPD, was also diminished due to the combined treatment of BCG with INH. A five fold increase of the dose of BCG did not overcome the effect of INH. INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced. Although INH concentrations in the urine were high at the onset of the instillation, in vitro experiments indicated that the effect of INH was probably not caused by killing of the BCG organisms shortly after application in the bladder. In conclusion, our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG. As this response may be important for the antitumor effect of BCG, urologists should be cautious with the prophylactic use of INH. The influence on the antitumor efficacy is now investigated in man. PMID- 1301590 TI - Karyometry of bladder washings for the follow up of patients with transitional cell carcinoma of the bladder. PMID- 1301591 TI - New approaches to intravesical chemo-immunotherapy in superficial bladder cancer. PMID- 1301592 TI - Disease-modifying anti-rheumatic drugs: strategies for screening. AB - Rheumatoid arthritis, a disease of unknown aetiology, has a multifactorial pathogenesis which may result in irreversible connective tissue destruction and loss of joint function. The search for drugs which offer more than symptomatic relief is a long term, largely unachieved aim of many pharmaceutical companies. This review briefly outlines those features of the aetiopathogenesis which appear to offer targets for therapeutic intervention and the structured strategy and test systems that can be used to detect drugs which may be capable of halting disease progression. PMID- 1301593 TI - 1-Beta-arabinofuranosylcytosine in therapy of leukemia: preclinical and clinical overview. AB - Although the mechanisms of therapeutic efficacy of cytosine arabinoside (Ara-C) are multifactorial, the pharmacodynamic basis for its cytotoxicity and therapeutic efficacy lies in its intracellular metabolism and the retention of the active metabolite, Ara-C triphosphate (Ara-CTP), which is a competitive inhibitor of DNA polymerase. Additional determinants of tumor cell sensitivity include Ara-CMP incorporation into cellular DNA, the size of the competing normal metabolite, deoxycytidine/5'-triphosphate pool, and the heterogeneity in growth kinetics of tumor cells, S-phase vs cells in other phases of the cell cycle. With high-dose Ara-C, substantial amounts of Ara-CTP are formed in phases of the cell cycle. The presence of high intracellular concentration with prolonged retention of Ara-CTP could lead to the inhibition of cell growth of the cells entering S phase as a consequence of inhibition of DNA-polymerase and/or incorporation into cellular DNA, resulting in a chain termination. Pharmacokinetically, Ara-C is rapidly eliminated from plasma. In mice, pharmacokinetic parameters of Ara-C are not sufficient predictors for the observed differences in their in vivo antitumor activity. Although these mice were bearing different tumor types (L1210 Ara-C sensitive or P-388 relatively more resistant), the observed differences in tumor response were achieved under identical plasma Ara-C concentrations and area under the concentration time curve. The observed antitumor activity in L1210 cells is primarily associated with higher Ara-CTP pools and retention (T1/2 > 4 hr) in tumor cells as compared with normal bone marrow cells. In the least responsive tumor (P-388), although Ara-CTP pools were sufficiently high, retention of the drug in tumor cells and in normal cells is poor with a T1/2 < 2 hr. Thus, unlike mice bearing leukemia L1210 cells, alteration of the mode and dose of administration of Ara-C in mice bearing P-388 could only result in increased host toxicity with no therapeutic gain. Similarly in patients with acute nonlymphocyte leukemia (ANLL), there is no significant correlation between plasma Ara-C concentration and the intracellular concentrations or retentions of Ara-CTP. In some patients the highest Ara-CTP pools in leukemic myeloblast cells are achieved at a lower level of plasma Ara-C and decrease further with the increase of plasma Ara-C. Thus, in the in vivo model system and in ANLL patients with no prior chemotherapy, Ara-CTP retention is a critical factor associated with response to this agent, in particular its direct association with duration of complete response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1301594 TI - Preclinical and clinical perspectives on the use of estramustine as an antimitotic drug. AB - A variety of cell biological, pharmacological, crystallographic and clinical approaches have indicated that the antimitotic drug estramustine has interesting and unusual properties. Although designed as an alkylating agent, the marked stability of the carbamate linkage to the steroid carrier molecule prevents the formation of alkylating intermediates. The affinity of the parent molecule for microtubule associated proteins and the concomitant antimicrotubule activity have cytotoxic consequences in tumor cells. Both preclinical and clinical studies of estramustine in combination with other antimicrotubule agents have shown that this approach has great potential to achieve therapeutic advantage, especially in disease states such as hormone refractory prostate cancer. PMID- 1301595 TI - Electrophysiology of cerebral blood vessels. AB - In spite of the relatively large amount of in vitro and in vivo data indicating that, in a number of ways, cerebral arteries are pharmacologically different from peripheral arteries, the mechanisms responsible for these differences are far from clear. An understanding of these mechanisms is particularly important for a rational approach to the treatment of disorders of the cerebral circulation including migraine, hypertension and the responses of cerebral vessels to subarachnoid haemorrhage. This review outlines electrophysiological data which are available from cerebrovascular smooth muscle cells, including the possibility that inwardly-rectifying potassium channels, active at potentials close to the resting membrane potential, are intimately involved in the changes in smooth muscle tone which couple blood flow to regional changes in nerve cell activity. The membrane potential changes in response to perivascular nerve stimulation, noradrenaline, 5-hydroxytryptamine and endothelium-derived hyperpolarizing factor are also described, together with the underlying membrane mechanisms and their relationship to smooth muscle contraction and relaxation. PMID- 1301596 TI - S-adenosylmethionine decarboxylase as an enzyme target for therapy. AB - The polyamine biosynthetic pathway has attracted much interest as a therapeutic target. Many studies have shown the potential value of inhibitors of the first enzyme in the biosynthetic pathway, ornithine decarboxylase, which forms putrescine. In order to convert putrescine into the polyamines, spermidine and spermine, the aminopropyl donor, decarboxylated S-adenosylmethionine, is needed. Therefore, S-adenosylmethionine decarboxylase (AdoMetDC, EC 4.1.1.50) is essential for polyamine synthesis. Early studies of the inhibition of this enzyme were carried out with compounds such as methylglyoxal bis(guanylhydrazone) that lack specificity and also lack potency since they are competitive inhibitors whose effects are overcome by a compensatory increase in the amount of the target enzyme. Recently, powerful irreversible inhibitors of AdoMetDC have become available including 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine, an enzyme activated inhibitor and 5'-deoxy-5'-[(3 hydrazinopropyl)methylamino]adenosine which binds to the active site and forms a covalent bond with the pyruvate prosthetic group. This review describes the current state of knowledge of the structure and properties of AdoMetDC, the available inhibitors of this enzyme, their mechanism of action and their effects on polyamines and on the growth of tumors and protozoan parasites. These effects indicate that AdoMetDC inhibitors may be of therapeutic value either alone or in combination with ornithine decarboxylase inhibitors and that further trials of these compounds should be considered. PMID- 1301597 TI - [Affective disorders in international classification of disorders ICD-10: classification of mental and behavioral disorders]. PMID- 1301598 TI - [Psychophysiological characteristics and metabolic indices of neurotransmitter metabolism in patients ill with endogenous depression]. AB - Research was conducted upon 28 patients with a diagnosis of endogenous depression after their pharmacological treatment with imipramine or chlorimipramine. The investigation considered the interrelationship between psychophysiological parameters (heart rate, respiration rhythm, postural muscular tension) and the indices of the cholinergic and adrenergic systems (kinetic parameters of choline transport in the blood; Vmax, the activity of plasmic pseudocholinesterase, Che; blood acetylcholinesterase AChE, monoaminoxidase in blood platelets, MAO; and dopamine beta hydroxylase DBH). The results indicate that during relapse of endogenous depression there occurs an imbalance in the cholinergic-adrenergic systems which may be the result of some somatic symptoms typically found in the depression syndrome. The appearance, after pharmacotherapy, of a correlation between the indices of the activity of the cholinergic system with the respiratory rhythm suggest that the part played by the cholinergic mechanism in the regulation of autonomic processes normalizes itself during the course of successful therapy. The appearance of characteristic correlations between the activity of the cholinergic and adrenergic systems and the psychophysiological parameters in the presence of relatively low psychological stress seems to accompany successful treatment with imipramine and chlorimipramine. PMID- 1301599 TI - [The analogous self-rating scale of affect as a tool in the assessment of change of clinical status of patients with endogenous depression syndrome. A comparison with the Hamilton depression scale]. AB - The authors compare the results of the analogous self-rating scale of affect with self report of affect (Hamilton Scale) in 57 patients with depression during the course of affective disorder. The ASRA seems to be particularly useful in the assessment of improvement in patients with slight or moderate depression. PMID- 1301600 TI - [Awareness of illness in affective psychosis]. AB - On the basis of analyzed clinical material several observations were attempted which were related to the patients' awareness of one's own affective psychosis. It was discovered that patients with endogenous depression considered themselves to be ill, but only in relation to depression. They usually do not perceive in themselves any psychotic illness. It was noticed that in depression past achievements appeared to be foreign to the patients. This was described in among other terms as "emotionally empty judgments". Analyzing the clinical picture of hypomanic states, stress was placed on the notion of the coexistence of logical thinking (and in some cases these thinking patterns are concerned with a feeling of heightened cognitive ability) with thinking styles based on logical errors. In all patients hypermnesia appears more important than other factors. The above mentioned phenomena are the subject of further research. PMID- 1301601 TI - [Disability among patients with affective disorders]. AB - In a group of patients with affective disorder it was found that the frequency of formal handicap occurred in 29.8% of those subjects. This was observed mainly in women and mostly with those diagnosed as bipolar affective disorder (43.6%). Patients with an alcohol problem more often were on social security pension. PMID- 1301602 TI - [The psychological health of offspring of patients suffering from endogenous affective disorder (II a follow-up study)]. AB - In the off-spring of patients with affective disorder various psychological disorders were found in 25% subjects. In the off-spring of healthy persons only 10% were found to have psychological disorders. PMID- 1301603 TI - [Selected demographic and clinical characteristics of patients with affective disorder treated in the Tworki Hospital in the years 1919- 1938 and 1947-1990]. AB - On the basis of medical records of 353 patients with affective disorder from the years 1919-1938 and 1947-1990 it was found that some demographic and clinical changes occurred. Amongst others there was observed a rise in the percentage of patients with depression from 1/3 to 2/3 and a fall in the number of patients suffering from mania. PMID- 1301605 TI - [Carbamazepine in the treatment of depressive syndromes]. AB - Carbamazepine treatment was used with 54 patients suffering from endogenous depression and organic depression. The anti-depressive effect was found to be the best in those patients with organic depression, while in endogenous depression it was better with bipolar affective disorder and with irregular EEG recordings. PMID- 1301604 TI - [The treatment of mixed affective syndromes]. PMID- 1301606 TI - [Ethyl alcohol and anti-depressive medication]. PMID- 1301607 TI - [Chronic hospitalizations in Poland from 1980 to 1989]. AB - The aim of the following research was to present and try to explain the features of chronic hospitalizations in psychiatric hospitals in Poland during the 1980's. According to the definition adopted when working with inpatients, patients hospitalized for over one year are regarded as chronic. The percentage of chronic patients in the general patient population was found to be 8% of all hospitalizations. The largest number of chronically hospitalized patients was found among those diagnosed as mentally retarded (29%) and schizophrenic (15%). The least number of chronic hospitalizations was found among patients with a diagnosis of alcoholism (1%) and among the non-psychotic patients (4%). In the years 1980 to 1989 there was a systematic fall in the previously increasing rate of chronic hospitalizations of people diagnoses as non-alcoholic psychotic and mentally retarded to about 70% of the number registered at the beginning of the decade. The fall in the rate of increase of chronic hospitalization is mainly due to the fall in the rate of growth of the chronically hospitalized group. This fall is not significantly connected with the movement of patients to community based services or with the increased mortality rate during the 1980's. The causes of this phenomenon remain unanswered. It may be the result of the better and more accessible forms of treatment, such as intermediate treatment, which are an alternative to long-term hospitalizations. Another reason may be the more effective forms of hospital treatment and the fact that psychiatric hospitals are using the "revolving door" strategy. PMID- 1301608 TI - [A study of involuntary treatment in psychiatric hospitals]. PMID- 1301609 TI - [A study of involuntary treatment in psychiatric hospitals]. AB - Research revealed that the only documented form of forced treatment was the use of mechanical restraining of patients. The frequency and circumstances of restraining patients were highly dependent on, among others, the structure of employment of hospital personnel. Research was conducted on 6962 patients from 6 psychiatric hospitals. It was revealed that during a month mechanical restraint was used with 5.5% of the patients. This percentage wavered from 1.6% to 8% in different hospitals. Isolation was not used at all. The frequency and circumstances of using force was significantly related to age, sex, marital status, the length of hospitalization and the diagnosis of the patient. Furthermore, the number of staff and the structure of employment in particular hospitals was important. PMID- 1301610 TI - [Diagnosis of borderline disorder in children and adolescents]. PMID- 1301611 TI - [Autism, infantile: diagnostic aspects]. AB - Autism is a rare disorder, whose frequency varies according to research from 0.7 to 4.5 per 10,000. The results of 40 children examined in the Out-patient Rehabilitation Union for Autistic Children showed that according to the DSM-III-R criteria 3 children suffered from autism. The authors suggest that the DSM-III-R criteria are either not known to the diagnosticians or are not used in the diagnosis. PMID- 1301612 TI - [A follow-up study of adolescents after suicide attempts]. AB - Young persons who in the past attempted suicide show the following characteristics: 1. they unwillingly make contact with an agency which they had consulted or had been treated due to their suicide attempt, 2. often maintain suicidal thoughts (11 of 37), 3. they have a higher estimation of their psychosocial situation then an objective assessment would indicate, 4. their psychosocial functioning does not improve with time. PMID- 1301613 TI - [Anorexia nervosa in a case of severe personality disorder]. PMID- 1301614 TI - [An attempt to formulate prognosis for anorexia nervosa on the basis of follow-up data]. AB - Follow-up data in the form of questionnaires were collected from 38 patients (36 women, 2 men) who had been treated for anorexia nervosa at the First Clinic of Mental Diseases of the Academy of Medicine in Gdansk from 1972 to 1988. The period of time of the follow-up was from 3 to 16 years. Adequate information was received from 16 patients (42%). One of the patients died and one was found to have developed a schizophrenic process. The 14 female patients were divided into 2 groups. Group 1 (7 persons) included patients whose anorectic symptoms abated. Three patients married and had children, five worked professionally. In group 2 (7 persons) anorectic symptoms persisted in a lesser degree. Two patients married and had children, five worked and two were on disability pensions. An analysis of both groups revealed that factors associated with poor prognosis in group 2 were: low motivation for accepting treatment, personality disorder partly due to organic factors, the use of laxatives and diuretics, continuing conflictive situations. PMID- 1301616 TI - [Norms of EEG sleep patterns for healthy Polish population aged from 20 to 59]. AB - Norms of sleep EEG patterns for a healthy population aged from 20 to 59 years are presented from which it was concluded that this age group forms a relatively stable pattern during the ontogenesis of sleep. The collected data were compared with data found in the literature. PMID- 1301615 TI - [The examination of mental status of children with multiple sclerosis]. AB - Assessment was conducted on 50 children with multiple sclerosis ranging in age from 3 to 16 years. The aim of the study was to the discover how they deviate from the norm in their mental status. It was concluded that the most frequent symptoms in this group of children, were various disorders in the impulsive- emotional sphere. It was noted that with time the chance of organic pathology increases. PMID- 1301617 TI - [Neurological symptoms during administration of electroconvulsive therapy]. PMID- 1301618 TI - [Electroconvulsive therapy administered to the elderly]. PMID- 1301619 TI - [Will electroconvulsive therapy induce seizures: magnetic brain stimulation as hypothesis of a new psychiatric therapy]. AB - This study presents a hypothesis of a new psychiatric therapy. Deep, low-rate transcranial magnetic stimulation is theoretically able to evoke the same therapeutic effects as electro-convulsive therapy but in a softer mode/painlessly and without a motor seizure. PMID- 1301620 TI - [Altered states of consciousness: a history of research]. AB - A history of studies on altered states of consciousness is described and divided into five main periods. Contemporary descriptive and psychophysiological research are reviewed. PMID- 1301621 TI - [Program fo the eradication of Cochliomyia hominivorax in Northern Africa]. AB - The New World Screwworm (NWS, Cochliomyia hominivorax) is an obligate parasite of warm-blooded animals. The female lays up to 300 eggs in any break in the skin, and the resulting larvae (screwworms) burrow into surrounding living flesh. Infested animals frequently die, while the annual cost of controlling the pest in domestic animals is about US $10 per head. NWS is endemic in tropical Latin America. In 1988, it was detected in Libya, presumable introduced with imported sheep. By 1990, the infestation had spread to an area of 25,000 km2 containing some 2 million livestock. In early 1991, an internationally funded eradication programme was undertaken by FAO, using sterile insects. Each week, 40 million pupae were flown from a production plant in Mexico, and the emerged adults were distributed by over the infested area. Within a few months, the infestation has been eradicated. Whereas 12,000 infested animals were found in 1990, only 6 were detected in 1991. The programme involved the shipping and distribution of 1.3 billion sterile insects, animal inspections totalling 40 million and laboratory examination of 280,000 trapped flies. While the programme cost close to US $75 million, a benefit/cost ration of 50:1 has been estimated. PMID- 1301622 TI - [Rift Valley fever in Madagascar in 1991. Sero-epidemiological studies in cattle]. AB - Rift Valley fever (RVF) virus was detected for the first time in Madagascar in 1979, but without any impact on human and animal populations. However, in 1990 and 1991, several outbreaks with massive cattle abortions were described. Since that period, seroepidemiological surveys have been conducted on the East coast and in the highlands (outbreak areas), in the high cattle density regions, and in the national slaughter house in Antananarivo. A high RVF IgM antibody prevalence was detected in the outbreak areas during the epizootics. This IgM prevalence thereafter decreased and was followed by an IgG high prevalence in all tested regions. Hypotheses on the occurrence of the virus in Madagascar, outbreak origins and virus circulation on the island are discussed. PMID- 1301623 TI - [Asymptomatic carrier state in Creole goats and cattle after recovery from Cowdria infection in Guadeloupe]. AB - Creole goats and cattle in Guadeloupe can be carriers of cowdriosis (heartwater: Cowdria ruminantium) after recovery for a period as long as 11 months in goats and 2 months in cattle. The carrier status was demonstrated by feeding Amblyomma variegatum nymphs on recovered animals and the resulting adult ticks on susceptible goats. Cowdria ruminantium was not detected permanently during the carrier status. PMID- 1301624 TI - Biotypes and sensitivity screening Yersinia enterocolitica as an infective agent in man and swine in Nigeria. AB - Diarrhoeic faecal samples from 210 humans and 192 swine were screened for Yersinia enterocolitica in 1990. Ten and 8 Y. enterocolitica strains were isolated from pig and man, respectively. The isolates were found to belong to Wauter's biotypes 1, 2, 3 and 4. Biotype 2 was isolated mainly from human stool samples. Biotype 3 was found only in swine while biotypes 1 and 4 were isolated from both man and swine. All the 18 strains showed varying degrees of sensitivity to antibiotics used in this investigation. The organisms were consistent in their resistance to ampicillin and penicillin. PMID- 1301625 TI - Salmonella enteritidis infection in the Sudan. AB - Twenty-one Salmonella enteritidis isolates were recovered from several poultry farms in three states in the Sudan over an eighteen-month period. The infection was disseminated from a distributing company which had imported infected fertilized eggs and parent stock. The Sudan S. enteritidis epidemic which devastated many poultry farms during 1990 was attributable and concurrent to that in Europe in particular and throughout the world in general. PMID- 1301626 TI - [Epidemiology of poultry parasitic disease in village breeding in Niamey area, Niger]. AB - An inventory of poultry parasitism in hens and Guinea fowls in village breeding was conducted from May 1985 to April 1987 in the Niamey department. About 1,200 post-mortem examinations and haematological tests, as well as 6,000 faecal egg counts were performed. The internal polyparasitism was observed in two thirds of the cases. Guinea fowls were more infected than chickens. Cestodiasis was frequent in both species. The omnipresent spirochaetosis made a potential danger for the improved flocks. Ectoparasitoses were mainly represented by argas and scaly-legs, which affected one chicken out of ten. PMID- 1301627 TI - Evaluation of mono- and polyclonal antibody-based antigen detection immunoassays for diagnosis of Trypanosoma evansi infection in the dromedary camel. AB - Two enzyme-linked immunosorbent assays (ELISA), one based on a mouse anti Trypanosoma brucei group-specific monoclonal antibody and the other on rabbit anti-Trypanosoma evansi polyclonal antibodies, have been evaluated for their ability to detect circulating trypanosome antigens in camel sera as a means for the diagnosis of T. evansi infections. All 91 sera from a negative control camel herd from Kenya gave negative antigen-ELISA results in the monoclonal antibody based ELISA and only 2 of them (2.2%) gave false positive results in the polyclonal antibody-based ELISA. In subsequent analyses of sera from infected camels (as determined by mouse inoculation), the monoclonal antibody-based ELISA detected antigens in 90 (83.3%) out of the 108 sera tested. This percentage was lower for the polyclonal antibody-based ELISA which was able to detect antigens in 67 (60.9%) out of the 110 sera tested. The two tests detected probably different antigens and when the results were combined, 99 out of 107 (92.5%) sera were shown to be ELISA positive. In a survey involving 316 camels from the Gao and Nara areas, in Mali, a high proportion of animals tested were antigen positive (43.5 and 42.9%, respectively for the mono- and polyclonal antibody based ELISA) compared to only 22 (7.0%) diagnosed by the parasite detection techniques. Thus, these immunoassays were at least six times more sensitive than the haematocrit centrifugation technique. As a large proportion of cases may be antigen positive but parasite negative, these two of "surra" immunoassays should be used in routine diagnosis in addition to the parasite detection techniques in the dromedary camel. PMID- 1301628 TI - [Trypanosomiasis and trypanocidal treatments in Ndama calves in a glossina infected area (the ranch of Madina-Diassa in Mali)]. AB - This work aims at contributing to the knowledge of trypanosomiasis epidemiology in calves of trypanotolerant breeds and at defining an appropriate treatment to improve the survival of such calves in a tsetse infested area. The first study was a parasitological survey of 100 calves from the day of birth to the age of one year. According to the results of this survey, the period from birth to three months is a "critical" moment in the life of the calves, due to a high infection rate and mortality related to trypanosomiasis. The purpose of the second study was to investigate the possible interference of early trypanocidal treatments with the further expression of trypanotolerance. For this purpose three groups of over one-year old animals were established. The groups had different trypanosomiasis history due to the different treatments they had undergone during their first year of life. All the animals had been exposed to trypanosomiasis without treatment and followed up parasitologically and clinically during the second year. The results showed no interference of early trypanocidal treatments (including preventive ones) with the expression of resistance in potentially trypanotolerant animals. PMID- 1301629 TI - Decrease of phosphofructokinase activity in relation to the pathogenesis of triorthocresyl-phosphate-induced delayed neuropathy. AB - The in vivo effect of a single dose of the neuropathic compound triorthocresyl phosphate (TOCP) on phosphofructokinase (PFC, E.C. 2.7.1.11) and its relation with the initiation step (inhibition and aging of neuropathy target esterase, NTE) in the TOCP-induced delayed neuropathy have been studied. Hens were treated with a neurotoxic dose of TOCP (500 mg/kg, p.o.) and with a protective compound (Phenylmethanesulfonyl fluoride, PMSF, 30 mg/kg s.c.) in different combinations: TOCP, TOCP + PMSF, PMSF + TOCP and PMSF. PFK activity was determined in brain and sciatic nerve 1, 3, 7 and 15 days after treatment. PFK activity decreased in sciatic nerve 15 days after dosing with TOCP or TOCP + PMSF. When animals were dosed with the protective agent (PMSF) alone or before administering the neurotoxic compound, PFK activity was unaltered and clinical signs of neuropathy were absent. The data presented here suggest that phosphofructokinase is involved in the pathogenesis of the neuropathy induced by TOCP. PMID- 1301631 TI - R5020 enhances PGE2 stimulated steroidogenesis in cultured rat granulosa cells. AB - Progesterone biosynthesis and metabolization to 20 alpha-hydroxyprogesterone was stimulated in granulosa cells cultured in the presence of 20 ng/ml of follicle stimulating hormone (FSH) or increasing concentrations of PGE2 (10(-9)-10(-7)M). Concurrent treatment with the synthetic progestin R5020 (10(-6) M) enhanced the FSH or PGE2 stimulated progesterone and 20 alpha-hydroxyprogesterone accumulation in culture media, as well as delta 5-3 beta-hydroxysteroid dehydrogenase activity in granulosa cell homogenates. These findings may represent another example of an autocrine control mechanism in which the steroidogenic product of the granulosa cell exerts an ultra-short loop regulation of its own production. PMID- 1301630 TI - Differential effects of two alleles of the dy locus on the pituitary-testicular axis of mice. AB - Testicular function was studied in vivo and in vitro in adult male dy/dy and dy2J/dy2J dystrophic mice. The results demonstrate that testicular function in dy/dy mice is more affected. The basal levels of pituitary hormones measured were normal in dystrophic mice, except for the presence of hyperprolactinemia in dy/dy mice. In dy/dy mice testicular weight was diminished and a deficient transduction of the gonadotropic signal is present in vivo, accompanied by reduced efficiency of 17-hydroxylase and 17-hydroxysteroid dehydrogenase. In dy2J/dy2J mice the signal transduction is normal and the reduction in enzyme efficiency is limited to 17-hydroxysteroid dehydrogenase. The in vitro HCG-induced increases in production of testosterone (T) and estradiol (E2) were reduced in dy/dy/mice, and the data indicate a reduction of enzyme activity rather than in efficiency. In dy21/dy21/mice, HCG-induced T synthesis was increased, HCG-induced E2 synthesis was normal, but basal media E2 levels were reduced, with the in vitro efficiency of aromatase being suppressed under both basal and HCG-stimulated conditions, when compared to their normal littermates. PMID- 1301632 TI - HgCl2 inhibition of Na-independent L-proline transport in chicken proximal cecum. AB - The proximal cecum of 5- and 13-wk-old chickens takes up L-proline (Pro) by two saturable pathways that differ in their requirement of Na+. The kinetic properties of Pro influx in cecal segments incubated in Na(+)-free conditions, have been studied and the effect of HgCl2 on the uptake process has been tested. Experiments were carried out using an in vitro everted-sleeve method. Kinetic parameters were estimated by nonlinear regression analysis. One min Pro fluxes in tissues incubated in presence of HgCl2 fit a straight line, indicating that a Na independent saturable component was inhibited. Estimated Kd* values are the same in 5- and 13-wk-old chickens, 0.023 +/- 0.001 and 0.027 +/- 0.001 microliters.mg 1 x min-1, respectively. HgCl2-sensitive fluxes fit a Michaelis hyperbola, with similar Km* values, 4.85 +/- 1.86 (5-wk) and 9.47 +/- 3.0 (13-wk) mmol/l. However, Vmax* in 5-wk chickens (0.662 +/- 0.053 nmol.mg-1 x min-1) is higher than in 13-wk birds (0.420 +/- 0.039), in accordance with previous results. The present data give further support to the existence of a Na-independent L-proline carrier in the chicken proximal cecum which is inhibitable by HgCl2. PMID- 1301633 TI - Effects of methyl palmoxirate on hypoxic rat atria. AB - Isolated rat atria in hypoxia released lactate into the bathing medium and underwent a decline of the contraction frequency which, in some cases led to a complete cessation of the pacemaker activity. A pronounced fall in the peak developed tension and a rise in the resting tension also appeared. The atria from 24 h fasted rats, which oxidize faster their reserve lipids than those from fed rats, exhibited greater functional disturbances during hypoxia, a lower lactate output and a smaller recovery of peak tension upon reoxygenation. Methyl palmoxirate, which is a selective inhibitor of carnitine palmitoyltransferase I, attenuated the decline of the beating rate and the rise of the resting tension in both groups of rats and the incidence of atrial arrest in the fasted rat group. The fall in the peak tension, lactate output and recovery upon reoxygenation were not altered by the inhibitor. These data indicate that methyl palmoxirate alleviates some of the hypoxic functional derangements. Hence, it may be inferred that inhibiting the oxidation of the fatty acid derived from the endogenous triacylglycerol is beneficial during oxygen-limited conditions and that these effects could not be ascribed to changes in the glycolytic flux. PMID- 1301634 TI - Effects of atrial natriuretic peptide, angiotensin II and III on norepinephrine uptake in the rat adrenal medulla. AB - The effects of atrial natriuretic peptide (ANP), angiotensin II (ANG II) and angiotensin III (ANG III) on norepinephrine (NE) uptake were studied in the adrenal medulla of the rat. One microM ANG II and 10 microM ANG III decreased NE uptake while 10 nM and 100 nM ANP increased it. Subthreshold concentrations of ANP (1 nM) blunted the inhibitory effect of 1 microM ANG II but did not modify the inhibitory effect of 10 microM ANG III. The increasing effects of 100 nM ANP on NE uptake were partially reversed by subthreshold concentrations of ANG II (1 nM) and blunted by 1 nM ANG III. The interaction between ANP and the renin angiotensin system could contribute to modulate the sympathetic function in the adrenal medulla. PMID- 1301635 TI - Sensitivity to in vitro lipid peroxidation in liver and brain of aged rats. AB - Lipid peroxidation in rat liver and brain has been studied to see if it increases with old age. No significant differences in the level of endogenous, nonstimulated lipid peroxidation (TBA-RS) is found between 9 month-old (mature adults) and 28 month-old animals in liver or cerebral cortex. Liver homogenates subjected in vitro to an oxidative stress (ascorbate-Fe++), show a clearly slower peroxidation rate in old than in young animals. On the other hand, the in vitro peroxidation rate of cerebral homogenates was similar in young and old animals. The in vitro peroxidation rate was much higher in brain than in liver tissue. These results do not support the view that old rats liver and brain are more susceptible to free radical oxidative damage than those of young ones. PMID- 1301636 TI - Glucose absorption by the interposed colon segment after intestinal resection. AB - One of the proposed surgical treatments of Short Bowel Syndrome is the interposition of a distal colon segment between two portions of the remnant small intestine. This method proved to reverse the nutritional disorders caused by this morbid entity. Surgical technique consisted in an 80% small bowel resection and the interposition of a 3 cm segment of distal colon between the remaining jejunum and ileum. After 70 days, the animals were reoperated and the interposed and the distal colon were isolated and tied. By using the method of rapid and successive absorptions of a glucose solution through the intestinal lumen, the relations between the absorption curves of the interposed and the normal colon could be drawn. Results show that the interposed colon segment absorbs more glucose (mean = 1.43 +/- 1.16 mg/dl) than the distal colon (mean = 0.37 +/- 0.29 mg/dl) and that its absorption pattern is similar to the small bowel rather than the colon. These results allow the use of this method for further studies in which the interposed colon adaptation is studied with other nutrients and/or under specific conditions. PMID- 1301637 TI - Effect of centrifugation on amniotic fluid phospholipid composition. AB - The first step in the determination of phospholipid in amniotic fluid is generally the removal of cells and debris from the fluid by centrifugation. Low speed centrifugation of the supernatant is reported to have the same phospholipidic profile and L/S, PG/S and PI/S ratios similar to those of the uncentrifuged amniotic fluid sample. With high-speed centrifugation almost all the pulmonary surfactant seems to be recovered in pellet with the same characteristics as the uncentrifuged amniotic fluid. PMID- 1301638 TI - A rapid and sensitive method for HPLC cholesterol determination in bile. AB - A relatively little time consuming simple method based on the treatment of bile with cholesterol oxidase and subsequent high performance liquid chromatography measurement of the 3-ketocholesterol produced in order to determine the level of the cholesterol concentration is described. The method avoids bilirubin interferences, has high reproducibility and recovery assays give 100% values. It is highly sensitive and suitable for use in the determination of cholesterol concentrations in bile and other bilirubin containing biological fluids. PMID- 1301639 TI - [Epithelial effect of gallopamil (D-600) on the rat intestine]. PMID- 1301640 TI - [Drug treatment of perioperative pain]. AB - Several drugs and techniques have been developed to improve the quality of post operative analgesia. Opiates are always the first intention drugs, specially with new molecules (buprenorphine, nalbuphine ...). Paracetamol and non-steroid anti inflammatory drugs can be efficacious in the post operative period alone or as adjuvants. The alpha 2 adrenergic agonists use must be specify. The patient auto controlled administration and the transdermal administration of opiates are useful techniques to provide effective analgesia with optimal safety. PMID- 1301641 TI - [Local analgesic action by direct effect of pethidine on the nervous trunks]. AB - The aim of this paper is to study the analgesic effects of meperidine (pethidine) on nervous trunks. First we compared the analgesic effect of pethidine in surgery of knee and femur. Meperidine was randomly administered either by femoral block or intravenously. The onset of analgesia was shorter with femoral block (5 minutes against 146 minutes). In the surgery of shoulder, nerve block with meperidine was performed using intersclalenic block. Plasma concentrations ar lower (maximum of 0.29 mg per liter) than intravenous therapeutic concentrations (between 0.5 and 0.7 mg per liter). So we can conclude as do other papers, there is a direct effect of meperidine on nervous trunks. This effect is probably mediated by receptors located on nervous trunks. PMID- 1301642 TI - Pain management in cancer patients. AB - Cancer pain in general responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment, successfully controlling pain in 70 to 90% of patients. Some pains do not respond so well but can usually be ameliorated by the judicious use of adjuvant analgesics, non-drug measures and the active involvement of the multi-disciplinary team. PMID- 1301643 TI - Opiates and immune function. Consequences on infectious diseases with special reference to AIDS. AB - There is an increasingly body of evidence, obtained both in vitro and in vivo, showing that exogenous opioids have a variety of effects on cells of the immune system. The consequence is that opiates at pharmacological concentrations suppress cell-mediated immunity, as reflected by depressed T-dependent antibody production by B lymphocytes, altered T lymphocyte functions such as proliferation, delayed-type hypersensitivity, graft-versus-host responses and decreased cytotoxic NK cell activity. The macrophage/monocyte oxidative burst and phagocytosis are also impaired, effects probably mediated by various opioid receptor types as they are blocked or reversed by naloxone, an opioid antagonist. Other possible mechanisms of interaction remain to be elucidated: exogenous opioids can act on neurons of the central nervous system, thereby activating the neuroendocrine system with a subsequent increase in serum glucocorticoid levels. Another potential link between the central nervous system and lymphoid tissue is the sympathetic nervous system, via which opioid-induced activation could result in noradrenergic inhibition of the immune system. The clinical consequences of these suppressive effects on the immune system are seen in the striking increase in the incidence of infections in intravenous opioid addicts. The advent of AIDS and the identification of intravenous drug abusers as a critical risk group have propelled interest in this area. Data obtained both in vitro and in vivo with various experimental models shows that morphine increases susceptibility to bacterial and viral infections, the latter effect possibly being related to a depressive effect of opioids on gamma-interferon levels. The dosage and time of administration strongly influence the results: it appears that chronic opioid treatment in vivo induces a state of immune tolerance, with normal resistance to viral infections, whereas short or single administration has a detrimental effect. In the former context, other factors such as a morphine-induced increase in CD4+ cell numbers may tend to enhance the infectivity of HIV-infected subjects. PMID- 1301644 TI - [Pharmacology of imidazoline receptors and cardiovascular regulation. Imidazoline receptors and blood pressure]. AB - To explain the central hypotensive action of clonidine- and rilmenidine-type drugs, a recent hypothesis suggested the involvement of imidazoline preferring receptors (IPR) insensitive to catecholamines. Binding studies performed on neuronal membranes prepared from the human Nucleus Reticularis Lateralis area (NRL) showed that rilmenidine was twice as selective as clonidine for the medullary IPRs. Voltammetric experiments revealed that these substances preferentially inhibited the activity of catecholaminergic neurones within the NRL, privileged site for their hypotensive action, rather than the activity of the neurones of the Locus Coeruleus (LC) where these drugs induce their sedative effect. The mechanism of the inhibitory action of these compounds upon the neurones of the NRL definitely involved IPRs when the inhibition of the LC neurones involved classical alpha-2-adrenoceptors. These functional studies also showed that rilmenidine exhibited a selectivity twice as important as clonidine, the reference substance. Poly- and monoclonal anticlonidine antibodies cross reacting only with imidazolines allowed to detect and immunoreactive substance in the human serum. The amounts of that substance thus measured were higher in some hypertensive patients than in normotensive subjects. The identity of that immunoreactive substance with "endazoline", the endogenous ligand of the IPRs, is presently analysed. PMID- 1301645 TI - [Study of induced effects by selective CCKB agonists cholecystokinin in the nociception and behavior in rodents]. AB - Potent and selective CCK-B agonists with good bioavailability have been designed by modifying the natural CCK-8 peptide. Thus, BC 264 [Boc-Tyr(SO3H)-gNle-mGly-Trp Me(Nle)-Asp-PheNH2] is a highly potent (0.15 nM) and selective agonist for CCK-B receptors which cross the blood brain barrier. Following i.v. injection of [3H]pBC 264 in mouse, the ligand was found in its intact form in brain tissue. Analgesic studies and in vivo binding experiments have shown that the CCKergic system could modify the release of endogenous enkephalins, whereas mu and delta opioid receptor activation modulates the release of endogenous CCK. Behavioural studies performed after local injection of CCK-8 or BC 264 into the postero median part of the nucleus accumbens have shown the involvement of CCK-A receptors in motivation and/or emotional states of rats. In the anterior part, CCK-B receptor stimulation could be involved in attention and memory processes. BC 264 systemically administered in mice increased fear and/or "anxiety" in the black and white box test. In the elevated plus maze, BC 264 increased the emotional responses of the "anxious" rat and decreased these responses in "non anxious" animals. These results suggest that endogenous CCK could play a critical role in mood modulation through CCK-A/CCK-B receptor stimulation. Dysfunctioning of the CCK-A/CCK-B pathways could be implicated in anxiety and panic attacks. PMID- 1301646 TI - [Cholecystokinins and their receptors. Functional aspects]. AB - The term cholecystokinin (CCK) refers to a family of related peptides whose members play hormonal roles in the gastro-intestinal tract. The sulfated octapeptide CCK-8 [Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] is also abundant throughout the central nervous system where it satisfies the criteria for a neurotransmitter. CCK interacts with at least two types of receptor called CCK-A and CCK-B receptors. These binding sites can be distinguished on the basis of their affinities for different molecular forms of CCK. Moreover, selective nonpeptide antagonists have been developed for CCK-A and CCK-B receptors. CCK-A receptors occur predominantly at the peripheral level where they are responsible for the digestive effects of CCK: intestinal and biliary smooth muscle contraction, pancreatic enzyme secretion, trophic effects on gastric and intestinal mucosa and regulation of feeding. Some brain CCK-receptors belong to the A-type, but the majority of them are CCK-B receptors. High densities of brain CCK-B receptors are present in cortical and limbic areas such as the amygdala and the hippocampus. At the peripheral level, CCK-B receptor antagonists are active on gastrin receptors, and these two receptors are similar if not identical. Experimental evidence suggests involvement of brain CCK processes in 4 domains: modulation of dopaminergic function, control of pain sensation, anxiety and memory formation. Thus, CCK-B antagonists may be useful to treat certain neuropathological conditions associated with CCK dysfunction. PMID- 1301647 TI - [Control program of interlaboratory quality for the assay of cyclosporine in biological fluids]. AB - The following article deals with the quality control program proposed since 1988 to the French laboratories performing the measurement of cyclosporine concentration in whole blood or in plasma. First, we describe how the program was organized and its evolution over time. Second, we discuss the main results generated. Those results enable us to state positively that the methods in use at present in the laboratories are precise and give highly reproducible results. PMID- 1301648 TI - [Acute hepatitis induced by deferoxamine in a patient under chronic hemodialysis]. PMID- 1301650 TI - [A rapid method for the determination of the anti-interferon activity of bacteria]. AB - Methods for the rapid and immediate determination of the anti-interferon activity of bacteria have been developed. The use of these methods makes it possible to reduce the time of determination from 48 hours to 24 and 7 hours. The proposed methods require no additional production costs, while their sensitivity and specificity are not inferior to those ensured by the classical method. These methods are recommended for the etiological diagnosis of diseases caused by opportunistic enterobacteria. PMID- 1301649 TI - [Buprenorphine abuse in a series of 50 drug addicts hospitalized at a Drug Dependence Evaluation hospital in Marseille]. AB - Buprenorphine, a synthetic central analgesic, marketed since 1987, was rapidly suspected to be subject to abuse. We tried to confirm this abuse in the context of our analytical activity at the Drug Dependence Evaluation and Information Centre. The study was based on 50 drug addicts admitted to Marseille Hospital between June and October 1992. Buprenorphine and its N-dealkylated metabolite were identified in the urine by high performance liquid chromatography equipped with a diode array detector. Nine (18%) of the 50 samples analysed were positive for buprenorphine and/or norbuprenorphine, with a confidence interval of 8 to 28%, which confirms the existence of abuse of this analgesic. PMID- 1301651 TI - [The effect of Lactobacillus acidophilus "Solco" on the immunological indices of totally decontaminated mice under complete gnotobiological isolation]. AB - The possibility of stimulating the immunity of totally decontaminated mice, kept isolated under germ-free conditions, with the use of killed L. acidophilus Solco strains has been studied. As revealed in this study, the oral and intraperitoneal administration of strains O1 and O6 to mice leads to a significant increase in the content of immunoglobulin-synthesizing cells in the jejunal lamina propria of the animals. The oral administration of L. acidophilus Solco strain O6 and the intraperitoneal injection of L. acidophilus Solco strain O1 have been found to lead to a significant rise in the level of luminol-dependent chemiluminescence of mouse peritoneal macrophages. The total decontamination of mice induces the development of secondary immunodeficiency which influences the effectiveness of immunostimulating agents. PMID- 1301652 TI - [The production of toxic shock syndrome toxins and enterotoxins by Staphylococcus aureus]. AB - The production of toxins of the toxic shock syndrome and enterotoxins by S. aureus of clinical origin was studied by means of commercial standard antisera and standard toxins. The study revealed that among 511 strains isolated in Russia toxigenic ones constituted 41%, and among 592 strains isolated in Czechia toxigenic ones constituted 63%. The capacity for producing toxins may be used as an epidemiological marker. PMID- 1301653 TI - [The dynamics of detecting group-A streptococci in an infectious disease clinic]. AB - The study revealed that the isolation rate of group A streptococci in scarlet fever patients at the time of hospitalization did not exceed 68%. The isolation rate of these streptococci was greatly influenced by antibacterial therapy carried out before hospitalization. Under clinical conditions with intensive penicillin therapy group A streptococci were eliminated from the larynx on days 3 4. In 13% of children repeated streptococcal infection was observed 0.5-3 months after discharge from hospital. PMID- 1301655 TI - [The prevalence and etiological structure of viral hepatitis in a climatic geographic area at high risk for infection]. AB - The spread of viral hepatitides on the territory of Central Asia has been analyzed, taking into account regional and territorial factors and using the Fergana Valley as an example. The analysis, based on the use of modern immunochemical, clinico-epidemiological and biochemical criteria, has made it possible to determine the etiological structure of viral hepatitides on the territory of the Fergana Valley. The epidemic outbreak on this territory has been proved to be caused by viral hepatitis E. The necessity of organizing constant epidemiological monitoring on the interstate and territorial level has been substantiated. PMID- 1301654 TI - [The first case of HIV infection in a citizen of the USSR]. AB - The first AIDS patient was a homosexual male who contacted HIV infection in 1982 in Tanzania. In December 1985 the first sign of Kaposi's sarcoma was noted in this patient. HIV infection was diagnosed in him only in February 1987. He was treated with AZT, reaferon, immunoglobulin and underwent electronic therapy. His state of health was stable till February 1991. Then he got severe bacterial pneumonia, candidosis. Pancytopenia progressed. The dose of AZT (0.8 g daily) was increased and intensive antibiotic therapy and the course of diflucan were prescribed. In spite of this treatment the number of CD4 lymphocytes catastrophically decreased (CD4 = 0.01 x 10(9)/l) and the patient died. Thus, more than 63 months passed from the date of the appearance of the first symptoms of AIDS in the patient to his death. PMID- 1301656 TI - [The use of programmed microcomputers for retrospective epidemiological analysis]. AB - In this article two programs for programmed microcalculators, models Elektronika MK-61 and Elektronika MK-52, manufactured in the USSR, are presented. These programs permit the determination of indices describing the dynamics of the epidemic process, both annual and for several years. PMID- 1301657 TI - [The evolution of meningococcal infection in Mongolia]. AB - On the basis of the generalization and analysis of the results of bacteriological and immunological investigations the epidemic process of meningococcal infection (MI) in Mongolia was found to undergo definite changes during the last 20 years. Group A meningococci prevailing in the etiology of MI were replaced by strains belonging to group B affecting mainly young children (aged up to 3 years). MI morbidity rate caused by group B meningococci was found to be higher in Mongolia than in other countries of the world. These data substantiate the necessity of using more effective remedies for the control of this infection and, in particular, specific immunization with vaccines against group B meningococci; profound study of the properties of the circulating meningococcal strains is to be carried out. PMID- 1301658 TI - [The laboratory epidemiological study of the joint circulation of the influenza virus A subtypes A/H1N1/ and A/H3N2/ in Bulgaria]. AB - The National Influenza Center of Bulgaria made the epidemiological analysis of the spread of influenza virus, type A, for the period of 11 years on the basis of mass laboratory investigations. Subtype A (H1N1) was found to be the main factor of epidemics in 1978 and 1982, while the epidemics of 1980, 1983, 1985, 1986, 1987 and 1988 were mainly caused by subtype A (H3N2). The data of laboratory and epidemiological studies indicated that after 20-year absence influenza virus A, subtype A (H1N1), was found again to circulate among the population of Bulgaria, and in 1978-1988 circulated simultaneously with the previous subtype A (H3N2). The simultaneous circulation of two subtypes of influenza virus was of great importance for the frequency, spread and duration of influenza epidemics. PMID- 1301659 TI - [The leading routes and factors in the transmission of the causative agent of campylobacteriosis under current conditions]. AB - Epidemiological investigations carried out at the foci of Campylobacter infection in Moscow and the Moscow region in 1987-1990 demonstrated that Campylobacter infection was recently registered as sporadic cases in a few foci. The alimentary route of the transmission of this infection was the main factor of its spread. A high role of everyday contacts in the spread of this infection was noted. The possibility for outbreaks and sporadic cases of Campylobacter infection to be masked by very frequently occurring associations of these bacteria is discussed. PMID- 1301660 TI - [The relationship of the antigenic characteristics of the tick-borne encephalitis virus to the level of the protective activity of inactivated cultured vaccines]. AB - As shown in this study, the immunization of animals with killed vaccines against tick-borne encephalitis (TBE) leads to the formation of specific immunity, depending on the antigenic structure of the vaccine strain and the test strains used for challenge. Vaccines obtained on the basis of the TBE virus strain of the Eastern antigenic variant induced the development of a wider spectrum of specific protective activity than vaccines obtained on the basis of the TBE virus strain of the Western antigenic variant. PMID- 1301661 TI - [Specific circulating immune complexes and antibody titers in candidiasis]. AB - Titers of antibodies to Candida albicans and specific circulating immune complexes have been studied in patients with chronic candidiasis of the genitals, skin and mucous membranes. In most patients with candidiasis of the skin and mucous membranes specific immune complexes have been detected in the blood serum; their determination increases the diagnostic value of serological tests in this disease. PMID- 1301662 TI - [The use of solid-phase liposomal immunoassay for determining a bacterial antigen of lipopolysaccharide nature]. AB - The solid-phase liposomal immunoassay procedure for the determination of Francisella tularensis lipopolysaccharide (LPS) has been developed. This assay has been made with the use of monolayer liposomes, on the average, 360 nm in diameter with their phospholipid bilayer modified with F. tularensis LPS and their internal space filled with calcein used as fluorescent marker. The assay is based on the principle of the competitive immunosorption of liposomes and antigenic LPS on the surface of polystyrene plates sensitized with specific monoclonal antibodies. The dynamic range of the method is 50-2,500 mg/ml, the variation index being 2.3-11.5%. Optimization of this method and its comparison with the enzyme immunoassay system for the given antigen-antibody pair has been made. PMID- 1301663 TI - [The immunochemical and biological properties of Leptospira membranes]. AB - The immunochemical and biological properties of purified membrane fractions obtained from Leptospira interrogans, serovar copenhageni, strain Rat 2, and Leptospira biflexa, strain Patoc 1, were studied. The presence of genus-specific and group-specific antigens in leptospiral membranes was established by the methods of immunodiffusion analysis, the microagglutination (MA) and lysis tests. In animal experiments cell membrane preparations produced no toxic and allergic effects. Leptospiral membranes obtained from strain Rat 2 ensured the protection of golden hamsters infected with Leptospira virulent culture and induced antibody production in high titers, detected with the use of the MA test, the lysis test and the enzyme immunoassay, in rabbits immunized in two injections. PMID- 1301664 TI - [A comparative cytofluorimetric analysis of the blood leukocytes in guinea pigs exposed to the phospholipase D and antigens of the causative agent of plague]. AB - The influence of Y. pestis phospholipase D on the physiological state of leukocytes in the blood of guinea pigs was studied in vivo by flow impulse fluorometry with the use of fluorochrome acridine orange. During the first hours of observation the intensity of leukocyte fluorescence increased due to a rise in the number of polymorphonuclear leukocytes and changes in the permeability of cell membranes. Further changes in the intensity of the fluorescence of the material under study after 24 hours of observation occurred due to the appearance of activated lymphocytes in the blood stream. The processes normalized by day 21. The reaction of blood leukocytes to phospholipase D was specific in comparison with the reaction to capsular antigen, "mouse" toxin, lipopolysaccharide and the main somatic antigen. PMID- 1301665 TI - [The evaluation of the vibriocidal antibody test in establishing a diagnosis of cholera or Vibrio carriage]. AB - On the basis of the serological survey of cholera patients, vibrio carriers and persons having had contacts with the source or reservoir of Vibrio cholerae the conclusion has been made that the test for the presence of vibriocidal antibodies, together with the bacteriological study of the patient, is of diagnostic importance in the diagnosis of cholera or vibrio carriership. The detection of vibriocidal antibodies, especially in the study of paired sera, permits the detection of cholera cases which have not been bacteriologically confirmed due to various reasons; besides, it makes it possible to exclude the diagnosis of cholera made only on the basis of clinical data. Like bacteriological study, the determination of vibriocidal antibodies must be obligatory for persons hospitalized in a provisory hospital or an isolation ward; it will undoubtedly improve the quality of cholera diagnosis and permit taking timely antiepidemic measures in the focus of infection. PMID- 1301666 TI - [The clinical assessment of macrophage functional activity in patients with protracted dysentery and its correction with lysozyme and vitamin E]. AB - Prospects for the correction of disturbances in the macrophagal system with a combination of lysozyme and vitamin E in patients with a protracted course of dysentery caused by Shigella flexneri 1b were studied. The phagocytic activity of macrophages (PAM) was found to be suppressed as early as at the beginning of the disease. Out of 38 persons repeatedly found to release shigellae 24 were administered polychemotherapy. PAM indices in patients treated with lysozyme and tocopherol acetate were likely to normalize, this being indicative of the positive effect of these preparations on the functional activity of the macrophagal system. PMID- 1301667 TI - [Genetic approaches to the study of meningococci]. PMID- 1301668 TI - [AIDS and mycobacterial infections]. PMID- 1301669 TI - [The sensitivity of bacterial strains of Yersinia pestis isolated from voles to normal human serum]. AB - The work deals with the results of the study of the viability of Y. pestis strains, isolated from voles in different natural foci of plague, in human normal serum (HNS) and its dependence on the assimilation of ions of exogenic iron. The cultures isolated at the Transcaucasian mountain focus of infection and having no small plasmid pYP were found highly sensitive to HNS. The introduction of the sources of iron, such as hemoglobin or ferritin, into the serum decreased its bactericidal effect. PMID- 1301670 TI - [The program for early diagnosis of the upper respiratory tract and digestive system neoplasms offered to alcoholics in the region of Friuli-Venice Giulia]. AB - The present study deals with data from an on-going collaborative programme of early diagnosis for upper aero-digestive tract tumors established since 1990 by three ENT Departments of the Friuli-Venezia Giulia Region, Northeastern Italy. The aim of the study was firstly to evaluate the socio-economic characteristics and clinical features of alcoholics in treatment who were offered a free ENT check-up, and secondly to test the feasibility of this type of referral of high risk patients from non-medical associations to the ENT specialist. A total of 683 patients, of which 151 (78%) were males and 151 (22%) were females, underwent ENT examination. About 25% of the patients were symptomatic, the most frequent symptom being dysphonia (50%) followed by cough (19%), while dyspnoea, dysphagia and pain were present in about 5% of the patients. Other than nearly 50% negative findings, ENT examination revealed a high percentage of inflammatory lesions (30%) of the upper aero-digestive tract. In 37 patients (6%) a precancerous lesion was found and in four cases an histologically confirmed tumor was diagnosed. Although the present study cannot be considered a complete screening, it did clearly evaluate the amount of response given by this high-risk population of alcoholics in treatment to the offer of an ENT examination and gives encouraging results concerning the feasibility of early diagnosis programmes for upper aero-digestive tract tumors which do not follow the normal routine of a sanitary referral by a general practitioner. PMID- 1301671 TI - [Ultrasound staging research of progressive pathology of the base of the tongue]. AB - Diagnosis of tongue tumours is often retarded mainly because tumours grow prevalently in deep muscular layers. A correct exploration of the region might be difficult solely employing clinical examination. Therefore, it would be useful to confirm the suspect of a neoplastic lesion at the base of the tongue with a promptly available imaging method. These considerations led us to evaluate ultrasonography (US) as a diagnostic tool for neoplastic lesions of this region. Initially 10 normal patients were studied in order to become familiar with US anatomy of the area. In a second phase our study involved 24 patients with diagnosed carcinoma of the tongue base and 26 patients with clinical suspect of neoplasm in the region. US examination was carried out with real-time equipment provided by a 5 Mhz convex transducer. Patients were examined in supine position with the neck hyperextended. Longitudinal, oblique and transverse scan of the submental region were obtained. The study showed that US gives detailed images of the floor of the mouth and the tongue. Neoplastic infiltration of the base of the tongue is clearly recognizable as a hypoechoic area. It was possible to detect masses ranging from 1.4 to 3.8 cm. In cases of larger lesions, US was useful in evaluating deep infiltration, whereas in other cases the method allowed the diagnosis of small lesions with submucosal growth. US did not proved to be highly reliable in the diagnosis of lesions confined to superficial planes (false negative results).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301672 TI - [Prospective, cohort, epidemiologic studies of laryngeal neoplasms in Italy]. AB - Recent epidemiological studies show, quite surprisingly, a regression in mortality rates for lung cancer in some of the most industrialized countries of the world. Aetiopathogenetic analogies are made by the Authors in order to verify future trends concerning the incidence of laryngeal cancer in Italy. In this study a particular study model, which furnishes incidence rate expectations for the disease, is elaborated. Comparison of relative risks according to birth dates demonstrates that people born around 1930 are in the higher risk range while younger generations seem to show an effective incidence reduction. Evaluations include that of estimating the period in which the world-wide incidence of the disease will be maximum. With the addition of 70 years (main incidence in the seventh decade) to the year 1930 (the worst year) the study predicts that the end of this century will see the most consistent accumulation of new cases. After the year 2010 a trend towards a gradual regression in incidence will appear. The reasons are probably related to the social and cultural transformations of the last twenty years, particularly the progressive abandoning of the smoking habit. PMID- 1301673 TI - [Positional rhinomanometry in hypertrophic vasomotor chronic rhinitis: considerations before and after functional surgery of turbinates]. AB - The Authors report their experience regarding Positional Active Rhinomanometry performed before and after surgery in hypertrophic-vasomotor chronic rhinitis. Twenty-five patients suffering of hypertrophy of the turbinates and/or nasal vasomotor disorders were examined pre-operatively and 3, 6 and 12 months after inferior submucosal turbinoplasty. Tests were performed in the seated, supina, homolateral and contralateral positions with regard to the fossa in question. Values were compared with those of forty normal subjects. Pre-operative examinations showed a large number of paradoxical responses and very high increase in nasal resistance. Postoperative values were quite similar to those of normal subjects, a demonstration of the efficacy of surgical treatment of turbinates hyper-reactivity. PMID- 1301674 TI - [Elaboration of the hearing disability scale]. AB - On the basis of a previous pilot study, a multiple-choice questionnaire regarding hearing disabilities was developed. The questionnaire (SDU) was made up of 20 items. The answers were tailored to the single question and scaled according to the increasing degree of disability (form A) or in random order (form B). Administration modality (self-report or interview) and form (A or B) were randomized in a group of 123 adult subjects with different degrees of hearing impairment. Only one factor, attributable to hearing disability, was extracted by factor analysis. This factor explains a major variance ratio of items related to speech perception in difficult listening context. A good correlation (r = .74) was found between SDU total score and hearing threshold in the better ear. No difference in mean score, variance and necessary scoring time of the SDU was found between form A and B. The Authors thus propose the use of form A because of a more easy computation of the total score. Self-report was more time consuming with respect to interview (11.7' vs. 8.4'). Furthermore, self-report was non possible in 13.8% of subjects for severe sign impairment and illiteracy and in 6.1% some form of support was necessary. No difference in mean score and variance between self-report and interview was found. SDU represent a tool for hearing disability evaluation useful in aural rehabilitation protocols. The principal advantage is high applicability thanks to the short time required, simplicity of task and flexibility of administration modality. PMID- 1301675 TI - [Cisplatin ototoxicity: the experience of the Institute of Oncology in Bari]. AB - The Authors report their experience, developed in the E.N.T. Unit of the Oncologic Institute of Bari, concerning the ototoxic effect of Diamminedichloroplatinum (CDDP). The Study was carried out on 74 patients with advanced cancer of the head and neck, treated according to the polychemotherapeutic scheme called "MBD" in 34 cases and in 40 cases according to the scheme called "Al Sarraf". The otologic evaluation was composed, in all the cases, of a complete series of audio-vestibular investigation, carried out prior to and immediately after every administration chemotherapy and periodically, during a 4 months period after interruption of therapy. Three patients (4%) showed significative acoustical damage, none showed vestibular deficit. Symptoms did not appear beyond the second administration of CDDP, which always followed subjective acouphenic symptomatology. The ototoxic effect of CDDP, resulting in the experience of the Oncologic Institute of Bari, is percentually very low: and seems to be influenced by the single dose, rather than by the total doses and in any case is not preventable by any profilatic measure. PMID- 1301676 TI - [Modification of vestibular function after radiation therapy for head and neck tumors]. AB - The effect of radiation on the vestibular apparatus of animals and man have not been widely investigate. Referred symptoms are disequilibrium and spontaneous nystagmus in animals while histological features are intralabyrinthic haemorrhage, edema of the endolymphatic spaces and alterations of sensory hair cells. A group of 20 patients with head and neck cancer located in different sites (nasal cavity, oropharynx, oral cavity, parotid gland) underwent to vestibular investigations before and 3-6 months after radiation therapy. Ten patients (50%) showed an alteration of the vestibular function of peripheral origin after radiation treatment. Complications appeared from a few weeks up to several months following termination of radiotherapy. The slow development of the lesion permitted central compensation. Few patients had symptoms and vestibular symptomatology was always of secondary importance with respect to the initial pathology. PMID- 1301677 TI - [Matter, antimatter and the void]. PMID- 1301678 TI - [The principle threats that damage the environment of our anthropologic system: their prevention]. PMID- 1301679 TI - [25 years of the eradication of malaria in Spain]. PMID- 1301680 TI - [The mystery of the function of the cerebellum]. PMID- 1301681 TI - [Chorioamnionitis]. PMID- 1301683 TI - [Nijmegen's syndrome]. PMID- 1301682 TI - [Surgery in portal hypertension (its historical evolution and the author's own experience)]. PMID- 1301684 TI - [Multiple congenital myofibromatosis]. PMID- 1301685 TI - [Chronic leg ulcer in children with prolidase deficiency]. PMID- 1301686 TI - [Collodion skin: a misdiagnosed but frequent clinical aspect of anhidrotic ectodermal dysplasia during the neonatal period]. PMID- 1301687 TI - [Xeroderma pigmentosum associated with Cockayne's syndrome]. PMID- 1301688 TI - [Necrobiotic xanthogranuloma with paraproteinemia]. PMID- 1301689 TI - [Cutaneous vasculitis with mixed cryoglobulinemia during chronic hepatitis C]. PMID- 1301690 TI - [Generalized leuko-melanodermal cutaneous amyloidosis]. PMID- 1301691 TI - [Primary nodular cutaneous amyloidosis with plasmacytic monotype]. PMID- 1301692 TI - [Apropos of papulous mucinosis: acral persistent papular mucinosis or minor form of scleromyxedema]. PMID- 1301693 TI - [Cutaneous manifestations of light chain deposition disease (Randall's syndrome)]. PMID- 1301694 TI - [Kawasaki syndrome in adults with perineal eruption]. PMID- 1301695 TI - [Pure cutaneous dermatomyositis and myasthenia]. PMID- 1301696 TI - [Cholesterol crystal emboli after fibrinolytic treatment]. PMID- 1301697 TI - [Granulomatous cheilitis with cutaneous extension in Crohn disease. Regression with hydroxychloroquine]. PMID- 1301698 TI - [Pyoderma gangrenosum aggravated by GM-CSF administration]. PMID- 1301699 TI - [A new case of paraneoplastic pemphigus]. PMID- 1301700 TI - [Cutaneous fungal embolism disclosing infection of aorto-iliac prosthesis]. PMID- 1301701 TI - [Severe Pasteurella multocida cellulitis. 2 cases]. PMID- 1301702 TI - [Necrotic vaccinia after immunotherapy in 2 AIDS patients]. PMID- 1301703 TI - [Chronic cutaneous candidiasis caused by Candida krusei]. PMID- 1301704 TI - [Unusual aspect of Pick-Herxheimer disease]. PMID- 1301705 TI - [Bacillary angiomatosis in acquired immunodeficiency syndrome. Isolation of the responsible organism blood]. PMID- 1301706 TI - [Cutaneo-muscular bacillary angiomatosis in a patient with AIDS. Therapeutic problems]. PMID- 1301707 TI - [Vesiculo-pustular cutaneous eruption disclosing primary infection by HIV virus]. PMID- 1301708 TI - [Cutaneous diphtheria in a patient with HIV infection]. PMID- 1301710 TI - [Edematous syndrome disclosing T-cell lymphoma]. PMID- 1301709 TI - [Mid-face malignant T-cell lymphoma (old malignant granuloma). A series of 4 cases with immunophenotyping and genotype study]. PMID- 1301711 TI - [T-cell cutaneous lymphoma: epidermal cysts, comedo and spinulous hyperkeratosis]. PMID- 1301712 TI - [Cutaneous lesions disclosing chronic myelomonocytic leukemia]. PMID- 1301713 TI - [Subcutaneous anaplastic Kil+ large cell lymphoma with clinical aspect of panniculitis]. PMID- 1301714 TI - [Anaplastic Kil+ large cell lymphoma with cutaneous metameric distribution]. PMID- 1301715 TI - [Sezary syndrome with palmoplantar bullous lesions]. PMID- 1301716 TI - [Multiple pilomatrixoma and myotonic dystrophy]. PMID- 1301717 TI - [Basal-cell and linear unilateral adnexal hamartoma (or linear unilateral basal cell nevus)]. PMID- 1301718 TI - [Eccrine angiomatous hamartoma in an adult after radiotherapy]. PMID- 1301719 TI - [Vitiligo-like lesions in melanoma treated with interleukin-2: 4 cases]. PMID- 1301720 TI - [Multifocal superficial cutaneous leiomyosarcoma]. PMID- 1301721 TI - [Benign lymphangio-endothelioma]. PMID- 1301722 TI - [Cutaneous complications after sleep electroencephalography]. PMID- 1301723 TI - [Necrotizing sialometaplasia of the palate: 3 cases]. PMID- 1301724 TI - [White fibrous papulosis of the neck: 2 Italian cases]. PMID- 1301725 TI - [Depigmentation of the skin and hair after phenobarbital induced eruption]. PMID- 1301726 TI - [Erythema multiforme caused by the combination of carbamazepine and cerebral irradiation]. PMID- 1301727 TI - [Granuloma-annulare type photosensitivity disorder caused by diclofenac]. PMID- 1301728 TI - [Value of cyclines in white sponge nevus]. PMID- 1301729 TI - [Lichenoid drug eruption after mesotherapy]. PMID- 1301730 TI - [Acquired acrokeratosis: mosaic acral keratosis?]. PMID- 1301731 TI - ["Vanishing" finger pads syndrome: localized acquired cutis laxa?]. PMID- 1301732 TI - Ecoepidemiology of leishmaniases in Syria. 3. Leishmania major infection in Psammomys obesus provides clues to life history of the rodent and possible control measures. AB - Collections of Psammomys obesus from near Damascus, Syria in May 1990 and November 1991 contained animals of all ages. Both series had a high prevalence of Leishmania major infection. Lesions were small in November and large in May. Assuming the two collections were representative of typical years, it is inferred that the breeding season is between October and May: there is high winter mortality of animals born early in the breeding season, but high survival of their parents, and there is high mortality in summer of animals aged between 17 and around 20 months. Transmission in summer is, therefore, between old adults shortly before their death and young adults born in late winter or spring. Juvenile animals are not exposed to the infection. If these findings are confirmed it should be relatively easy to break this tenuous cycle. PMID- 1301733 TI - Ivermectin in human onchocerciasis: a clinical-pathological study of skin lesions before and three days after treatment. AB - Findings are presented from an histological study of 360 skin-snips (from iliac crests, calves, ankles) taken from 30 Ivory Coast onchocerciasis patients before and three days after an oral dose of ivermectin (200 micrograms/kg). This dose causes a nearly complete disappearance of the intralymphatic microfilariae and, surprisingly, of the "extra-vascular" ones. That shows the difficulty to localize the microfilariae on histological sections; these microfilariae are in fact inside the lymphatic pre-capillaries. There was no intensification of acute skin lesions after the treatment, thus showing that, contrary to diethylcarbamazine (DEC), ivermectin does not induce an exit of microfilariae into the extralymphatic connective tissue. Under the influence of ivermectin, paralyzed microfilariae may be carried passively towards the deep sub-cutaneous lymphatics, and then destroyed inside the regional lymph nodes, without producing major changes in the skin. PMID- 1301734 TI - [Human simuliidosis in France: antiquity, anthropophilic species]. AB - The problem of the human Simuliidosis (caused by black flies) is reviewed for the France: important and, perhaps, relatively recent increase from the known human attacks by black flies. Countries and anthropophilic species are cited. PMID- 1301735 TI - Rejection of the "flying primate" hypothesis by phylogenetic evidence from the epsilon-globin gene. PMID- 1301736 TI - Veterinary services in the Northern Territory, 1824-1970. PMID- 1301739 TI - Recombinant cytochrome P-450 production in yeast. PMID- 1301737 TI - Engineering antibodies for therapy. AB - For most MAb-based therapies single doses of MAbs or MAb conjugates will not be curative. Rodent MAbs are highly immonogenic in almost all patients. The HAMA response abrogates efficacy and can cause toxicity in organs of clearance, especially for MAb-cytotoxic agent conjugates. Humanization is the most promising generally applicable approach to overcoming the immunogenicity of rodent MAbs. Chimerization reduces immunogenicity in patients significantly, but not completely. Full humanization of rodent antibodies with retention of most of their antigen binding activity is now a routine procedure. The studies with 4D5 (Kelley et al., 1992), however, illustrate that even when antigen binding activity is retained, humanization may affect the overall conformation of the antibody in ways which influence its interaction with cells (for example when the antigen is internalized or involved in signal transduction) and hence its in vivo properties. As yet there are not sufficient data to judge whether full humanization will (in practical terms) completely overcome the immunogenicity problem in patients, but these data will be available within a year. Antibody fragments are the most promising general approach to manipulating the pharmacokinetics and biodistribution of therapeutic MAbs. Such fragments are clearly superior to whole IgGs for tumour detection and will very likely prove superior for tumour therapy also. MAb targeting of highly potent cytotoxic agents to tumours represents a much-needed approach to improving therapeutic ratios in cancer treatment. Radioisotopes and highly potent low molecular weight drugs are the most promising cell-killing agents for MAb targeting, and conjugation technology suitable for clinical use of some of the best of these agents has now been developed. Very encouraging data have already been obtained in clinical studies of haematopoietic malignancies with MAb-isotope conjugates. Tumour loading data from clinical studies suggest that killing of solid tumours in patients will be achievable in the near future with repeated administration of humanized antibody fragments carrying the superior isotopes or highly potent drugs which are now available. PMID- 1301738 TI - Advances in structural understanding of lipases. PMID- 1301740 TI - Enzymatic synthesis of oligosaccharides. PMID- 1301741 TI - Lectin-mediated aggregation of yeasts--yeast flocculation. PMID- 1301742 TI - The polymerase chain reaction in molecular and micro-biology. PMID- 1301743 TI - Blood substitutes: engineering the haemoglobin molecule. PMID- 1301744 TI - Development and potential of genetically engineered viral insecticides. PMID- 1301745 TI - A study of RBC aggregation-sedimentation phenomenon with conductivity method. AB - In this paper, we present a conductivity method for measuring the RBC (red blood cell) aggregation-sedimentation phenomenon and the theoretical analysis of this phenomenon. A theory describing the RBC aggregation-sedimentation phenomenon with the conductivity method is proposed and the formula of the l-t function which depicts the RBC aggregation-sedimentation process is given. We put forward the aggregation index and sedimentation factor describing the RBC aggregation sedimentation phenomenon for the first time. PMID- 1301746 TI - Studies on transplantation of the laminin receptor and its roles in experimental metastasis of murine Lewis lung carcinoma cells. AB - The isolated laminin receptor (LN-R) labeled by 125I was reconstituted into liposomes. 125I-LN-R-liposomes and free 125I-LN-R were separated by Sepharose 4B column chromatography. The LN-R-liposomes showed affinity for laminin (LN) and were capable of binding to immobilized LN substrate. In order to make transplantation of LN-R, LN-R-liposomes were fused with cultured murine Lewis lung carcinoma cells with the help of polyethylene glycol (PEG) induction. The radiation with the fused cells was not removed by salt solution. The binding of the fused cells enriched in foreign LN-R to LN substrate increased by 87.5%. Furthermore, the murine Lewis lung carcinoma cells with and without transplanted LN-R were injected into C57BL/6J mice through tail veins (5 x 10(5) cells/each mouse) respectively. The mice in the test group died earlier than those in the control group. The total weight of lung tumor in the test group remarkably increased in comparison with those in the control group. The results taken together directly demonstrated that LN-R on carcinoma cell surface were involved in the recognition and binding of the cancer cells to LN in basement membranes, and also LN-R was of a crucial biological molecule in cancer metastasis. PMID- 1301748 TI - [Pollen morphology of medicinal flowers. I. The single-origin type]. PMID- 1301747 TI - [Re-discovery of yinzhou chaihu]. AB - This paper deals with the distribution, original plant, course of rise and fall in drug market and quality of Yinzhou Chaihu, which was once regarded as a fine sort of Chinese drug Chaihu (Radix Bupleuri) in ancient times. Further research on this medicinal plant is suggested to facilitate its re-exploitation and utilization. PMID- 1301749 TI - [Integrated control of pests injuring Chinese hawthorn Crataegus pinatifida Bge. var. major N.E.Br. by nonpollution techniques]. AB - Field experiments on integrated control of pests injuring Chinese hawthorn by some nonpollution techniques including agricultural biological and physical methods, were carried out in Xinglong County, Hebei Province during 1989-1991. Satisfactory results were obtained. Compared with synthetic pesticides, the new techniques improve the control effect by 30%-60% generally, increase the number of natural enemies by 51.26%-68.51%, and enhance the yield by 47.58%. The test shows that the hawthorns from the field treated by the new techniques are either free of pesticide residual or with a residual 500-1000 times less than the residual standard fixed by FAO/WHO or the state. PMID- 1301750 TI - [Studies of several factors bearing on tissue culture of Fritillaria thunbergii Miq]. PMID- 1301751 TI - [Comparison of glucoside content of bitter apricot seeds processed in different ways and stored routinely for one year]. PMID- 1301752 TI - [Preparation method and quality control of compound Daphne injection]. AB - Compound Daphne Injection (CDI) is a sterilized solution extracted and refined from Cortex Daphnes, Radix Gentianae Macrophyllae, Radix Angelicae Pubescentis and Radix Notopterygii. The preparation method and quality control of CDI are discussed in this paper. PMID- 1301753 TI - [Studies on dissolution of icariin from wuxian huichun capsules]. AB - The accumulated dissolution of icariin from the traditional Chinese Wuxian Huichun capsules has been determined by roll-basket and three-wavelength UV spectrophotometry within 100 minutes. The values of T50 and Td for samples c, d are significantly greater than those for a, b. It is thus essential to determine the dissolution as a means to control the quality of capsules. PMID- 1301754 TI - [Chemical constituents of Parthenocissus thomsonii (Laws.) Planch]. AB - Five compounds (1-5) were isolated from the leaves of Parthenocissus thomsonii collected in Henan. On the basis of chemical reaction and spectroscopic studies, 1, 2 and 3 were identified as friedelin, epifriedelanol and quercetin respectively. PMID- 1301755 TI - [Analysis of the volatile organic acids in 5 kinds of pericarpium Trichosanthis]. AB - The volatile organic acids in the pericarps of Trichosanthes kirilowii, T. rosthornii, T. truncata, T. hupehensis and T. cucumeroides (Cucurbitaceae) were analyzed by methylation, GC and GC-MS-DS. The results showed that they were composed of fifteen long-chain fatty acids, such as palmitic, linolenic, linoleic, lauric, myristic acid, etc. PMID- 1301756 TI - [Quantitative estimation of active principles polyphenols in green tea]. PMID- 1301757 TI - [Effects of tetramethylpyrazine and ferulic acid alone or combined on vascular smooth muscle, blood viscosity and toxicity]. AB - The experiments showed that both tetramethylpyrazine and ferulic acid relaxed the norepinephrine-induced spasmodic contraction of rabbit and rat aorta strips, increased the coronary flow of isolated guinea pig hearts and reduced the whole blood viscosity in rats. Evaluated with Burgi's equation, the combined effect of these 2 drugs was obviously potentiated, but the combined acute toxicity in mice was greatly reduced. PMID- 1301758 TI - [Effects of 3 Chinese medical prescriptions on alkaline reflux gastritis in rats]. AB - The experimental alkaline reflux gastritis in rats was established after 9 weeks of anastomosis between stomach and jejunum. The experiment shows that xiangsha liujunzi decoction, xiaochaihu decoction and dahuang gancao decoction all help to inhibit edema, hyperamia and extravasted blood, as well as depress inflammatory infiltration and hyperplasia. The number of intestinal metaplasia in the group treated with xiangsha liujunzi decoction is decreased. All the three prescriptions are not able to lower the contents of bile acid in the stomach. PMID- 1301759 TI - [Antiarrhythmic effects of crebanine]. AB - Crebanine (Cre) iv 5 mg/kg could convert BaCl2-induced arrhythmia into sinus rhythm in rats, and could significantly increase the tolerant dose of aconitine to produce ventricular fibrillation (VF) and cardiac arrest (CA) in rats. The drug could also decrease the incidence of VF and CA by CaCl2 in rats and by chloroform in mice, but had no protective effects on ouabain-induced arrhythmias in guinea pigs. PMID- 1301760 TI - [Effect of compound and minor prescription of heat-nature products radix Aconiti lateralis preparata, rhizoma Zingiberis and cortex Cinnamomi on the sympathetic nervous system, adrenal gland, TSH and LH]. AB - The effect of compound and minor prescriptions of Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis and Cortex Cinnamomi on sympathetic nervous system, adrenal gland, TSH and LH of rats was studied. Results showed that both prescriptions made the heart rate quicken, estrous cycle shorten, improved the adrenal cortex hormone and promote TSH and LH synthesis and secretion. The two Heat-nature products (Radix Aconiti Praeparata and Rhizoma Zingiberis) may be used instead of all the three products to make a Heat Syndrome animal model. PMID- 1301761 TI - [Experimental study of extracochlear electric stimulation]. AB - The efficiency and feasibility of chronic extracochlear implantation and electric stimulation were studied in two adult cats and four 2-month kittens. The first electrode was placed on the round window by fixing the lead wire on the bridge of aditus between the middle ear and bulla cavity; the second electrode was placed on the surface of the tympanic promontory; the third was inserted into the temporal muscle out of the bulla and the forth fixed in transverse sinus with dental cement. ABRs and EABRs were recorded pre- and postoperatively and during electric stimulation. The results indicated that: (1) The chronic electric stimulation could be carried on with round window electrode; the fixation of round window electrode is satisfactory without the influence of postnatal skull growth. (2) EABRs evoked by electrically stimulating round window electrode were mainly generated by the auditory system, but its short response was partly generated by the vestibular system. (3) EABRs evoked by electric stimulation of round window electrode were contaminated by facial nerve response which could be inhibited by 2% xylocaine injection of foramen stylomastoid. (4) The EABRs evoked by stimulating tympanic promontory electrode is uncertain. PMID- 1301762 TI - [Inner ear damage due to hyperlipidemia in the young and old guinea pigs]. AB - Nineteen guinea pigs of one month and 11 of 30 months were given high fat diet for 3 months to produce hyperlipidemia; 16 of them followed by 3 months' normal diet to resume blood lipid level; 27 for control. The results showed that: The serum cholesterol level of the experimental groups was markedly elevated (P < 0.01) with fatty degeneration of liver. Damages in OHC, IHC, cells of stria vascularis and few myelin sheaths of cochlear nerve were seen in all experimental animals, and the reduction of cochlear damages was not seen in those animals with blood lipid level resumed to normal. Auditory dysfunction was very marked as shown by ABR in the old animals with hyperlipidemia as compared with controls (P < 0.01). PMID- 1301763 TI - [Auditory middle latency response: a study of optimal measuring conditions and determination of normal values]. AB - The purposes of the present study were to select the optimal conditions for middle latency response (MLR) measuring with a statistical model of orthogonal test, and to determine the normal values of MLR. It showed that stimuli click and logon of different frequencies could be used to evoke MLR. The filter-setting was a significant factor in effecting the measurement of MLR. 30-50Hz or 30-100Hz was the most optimal filter-band. The effects of stimulus polarities on MLR bore no significant difference statistically. In clinical practice, stimulus repetition rate of 11/s was most desirable. We determined that mean thresholds of MLR were approximately 10dBnHL and latencies of wave Po, Na and Pa were approximately 10, 20 and 30ms respectively. The amplitudes of MLR varied greatly. PMID- 1301764 TI - [Electron microscopic observation on benign tumors of the facial nerve]. AB - Two cases of benign tumors of the facial nerve were examined. One was neurilemmoma and the other neurofibroma. The histopathological diagnoses of the tumors are difficult to make with light microscope. However, electron microscopy may be helpful. Under transmission electron microscope, the difference of two kinds of tumors is obvious. The main pathological features had been discussed. PMID- 1301765 TI - [Surgical treatment of cancer of the base of the tongue and epiglottis]. AB - This paper reports the surgical treatment of 10 cases of cancer of the base of the tongue and the epiglottis resected by a translaryngeal approach. In addition, a brief description of the technique is introduced. All patients had squamous cell cancer which was obviously advanced to stage IV and the tumor mass had extended to the whole root of the tongue, the vallecula and the epiglottis. After operation, all patients learned to swallow effectively and no persistent aspiration occurred. The speech articulation was satisfactory. Postoperative follow-up of all the patients, the shortest being 13 months, revealed no local or cervical lymphatic recurrence, but two patients died of lung metastasis, one after 18 months and the other after 48 months. The translaryngeal approach maintains the integrity of the mandibular and occlusal joints, avoids deformity to the face and the anterior oral cavity and prevents scarring in those tissues affording maximal mobility of the tongue. PMID- 1301766 TI - [Laryngeal carcinoma with laryngeal abscess]. AB - We had encountered 5 cases of laryngeal carcinoma associated with abscess. Four of them were advanced laryngeal cancer with abscess induced by mechanical injury, and one with post-radiation laryngeal perichondritis & abscess formation. Management included total laryngectomy in 3 patients, partial laryngectomy in 1 patient, and resection of post-radiation abscess in one. Laryngeal abscesses are seen rarely today. Endeavour should be made to decrease such complication. The authors had presented their experience in the management of laryngeal carcinoma associated with laryngeal abscess, together with a review of the history and some of the current ideas about this problem. PMID- 1301767 TI - [Langerhans cells in laryngeal carcinoma in relation to prognosis]. AB - Infiltration of Langerhans cells (LCs) was investigated by immunohistochemical methods with the use of anti-S100 protein in 25 cases of stage II and 50 cases of stage III laryngeal carcinoma. Varying population densities of S100 positive LCs were noted. LCs were mainly interspersed among the tumor cells. The prognosis of patients with stage II and stage III laryngeal carcinoma correlated well to the density of LCs in tumor tissue in patients with a marked infiltration of LCs, survival time was longer than in those cases with only a slight infiltration (P < 0.05). This indicates that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor in laryngeal carcinoma. PMID- 1301769 TI - [Communication barriers]. PMID- 1301768 TI - Cancer in the Nordic countries, 1981-86. A joint publication of the five Nordic Cancer Registries. PMID- 1301770 TI - [The shock of a seropositive diagnosis]. PMID- 1301771 TI - [Orientation of the nursing profession and nurses aides]. PMID- 1301772 TI - [Violence directed against aged persons, could it be by you?]. PMID- 1301773 TI - The nursing assistants' field of practice. PMID- 1301774 TI - Youth protection: a collective responsibility. PMID- 1301775 TI - Low-doses oral contraception benefits women over 40. PMID- 1301776 TI - [Rosacea--a chronic disease of the skin which, if not treated, can cause permanent damage]. PMID- 1301777 TI - [Baldness: when? How? Why?]. PMID- 1301778 TI - [Everyday speech]. PMID- 1301779 TI - A brief history of ocular toxicology. AB - The background leading to the need for ocular toxicity testing is reviewed. Awareness of side effects of various categories of drugs (e.g., steroids and cataracts) has provided impetus for examination of many categories of compounds including ocular drugs, cosmetics and household chemicals. The standard test (Draize) used for many years in the evaluation of ocular toxicity of many chemicals is being modified or replaced by other procedures. Modifications include volume and/or concentration reductions. Replacements include the use of in vitro systems of either freshly isolated tissues, tissue cultured cells, or non-living systems. The relative predictability of each approach is evaluated with the conclusion that only in vivo testing (albeit using low doses and low volumes) can reflect the full spectrum of potential responses. Each in vitro methodology has at least one drawback relative to in vivo test procedures. PMID- 1301780 TI - Status of in vitro ocular irritation testing. AB - This paper reviews advances in the validation of alternative methods for eye irritation testing since the 1987 publication, A Critical Evaluation of Alternatives to Acute Ocular Irritation Testing (1). We have highlighted details of methods that appear promising and identified the minimum needs and endpoints necessary to develop a battery or batteries of in vitro tests to evaluate eye irritancy. We have recommended a series of workshops to provide identified batteries for specific classes of chemicals or for specific uses of eye irritancy testing. We have also identified the need for consensus meetings and peer reviewed publication to ensure that the most predictive batteries become parts of validation studies. Finally, we note that academic scientists, industry, government and the animal protection community must work together in order to replace in vivo eye irritancy testing with appropriately validated in vitro methods. PMID- 1301781 TI - Action potential response of the corneal nerves to irritants. AB - The cornea, in addition to its refractive function for the eye, and by way of its very dense sensory innervation, serves a very important protective function for the visual organ. The cornea receives mainly sensory innervation from the first division of the trigeminal ganglion and a sparse amount of sympathetic fibers. The sensory nerves carry out their protective function by responding to various types of stimuli in a way so that they are all perceived psychologically as painful. Neurophysiological data indicates that, despite the morphological similarity of free-nerve endings in the cornea, they are differentiated functionally. A concentration series, (0.005 to 10% solution in saline), of various potential irritants (phosphate detergent, baby shampoo, liquid chlorine bleach, herbal shampoo, onion juice, SDS, and sodium chloride) was applied directly to the cornea of the anesthetized rabbit. Neural activity was assessed from extra-cellular records of long ciliary nerve over a ten second application period, and for ten seconds following stimulus removal. Baby shampoo was non stimulatory over the applied concentration range. Sodium chloride, on the other hand, exhibited linear response dynamics over the range of 0.01 to 5% (p < 0.001). SDS was highly stimulatory, but showed no predictable concentration or response relationship. All of the other irritants tested responded in a logarithmic fashion. This suggests that the application of neurophysiological techniques to assess the pain and potential inflammatory aspects of a substance for human use can be monitored in this fashion. Moreover, response profiles for various classes of compounds and homologous series, as well as pH and osmolality, can be established. PMID- 1301782 TI - Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic responses. AB - Target biomacromolecular assay systems utilize as endpoints quantifiable alterations in key macromolecules elicited by various chemicals and formulations. The EYTEX Assay System, an example of a target biomacromolecular test method, has been used to predict the in vivo ocular irritancy potential of chemicals and formulations. The biomacromolecular reagent is a standardized matrix which can be produced routinely. One hundred test chemicals, representing diverse chemical classes with a wide range of toxic responses in vivo, were evaluated in the EYTEX system. In vitro results were compared to maximum 24-hour Draize scores and Draize classifications. The concordance of the in vitro and in vivo results demonstrated the relevance of the alteration of the EYTEX macromolecular matrix to the prediction of in vivo ocular irritation. The relevance of the in vitro endpoint of turbidity of the EYTEX matrix to in vivo ocular irritation has thus been demonstrated for a large number of test agents in other evaluation studies (1, 2, 3, 4, 5, 6, 7, 8). Integration of macromolecular-based test methods with in vitro cytotoxicity or cellular response methods may provide complementary information about mechanisms of target-induced toxicity. The target biomacromolecular assay systems which provide standardized, reproducible reagents are valuable components of test batteries. PMID- 1301783 TI - In vitro methods: their relevance and complementarity in ocular safety assessment. AB - Ocular irritation includes a wide variety of mechanisms some of which can be explored by in vitro methods. For example, the effects on epithelial cells that constitute the outer layers of both the conjunctiva and the cornea may result in direct cytotoxicity or impairment of cellular functions -such as impermeability-, phenomena that can be explored in vitro. Irritancy may also involve inflammation of the conjunctival connective tissue and of the corneal stroma with its vascular and cellular features; effects on the stroma can lead to the opacification of the cornea; this last phenomenon may be the consequence of mechanisms such as modification of the structure of proteins or changes in stroma hydration which in particular is closely related to corneal endothelium metabolic activity. Recovery after eye injury depends partly on the extent of ocular damage and on the residual mitotic activity of the remaining cells. We have studied 41 surfactants, lotions and shampoos in 6 to 8 in vitro methods each one exploring one or two endpoints that could be linked to the ocular irritancy phenomena described above. In vivo ocular irritancy data for these materials from previous studies were compared to in vitro results. The results obtained show that -among the techniques that were investigated and for the categories of substances that were studied- the Het-CAM test and more particularly the endpoint that is related to vascular effects gives the best assessment of acute ocular irritancy (Spearman's rho coefficients between in vivo and in vitro data greater than 0.90); however, cell culture methods, especially one based on short contact time between cells and products and on evaluation of early toxic effects, also proved interesting (Spearman's rho coefficients between in vivo and in vitro data greater than 0.85). Moreover, the isolated cornea opacity and permeability test gave complementary information more related to recovery from surfactant-induced damage. These encouraging results lead us to consider in vitro ocular safety assessment with optimism for the categories of products investigated. PMID- 1301784 TI - Alternatives to ocular irritation testing in animals. AB - The preliminary conclusions of a survey of possible non-animal alternatives to the Draize rabbit eye irritancy test, recently conducted for the Commission of the European Communities, are presented. The various types of alternatives to animal tests are reviewed in terms of their current state of development and validation, and also their potential in relation to the type of exposure, level of testing, type of testing, type of effect, location of effect, and type of test material. Various problems concerning the availability and quality of in vivo eye irritation data, and the use of this data in in vitro/in vivo comparisons, are highlighted. Finally, the use of step-wise and integrated animal/non-animal and non-animal/non-animal test systems and strategies are discussed. PMID- 1301785 TI - The status of eye irritancy testing: a regulatory perspective. AB - Eye irritation testing is a salient public issue and continues to escalate on the public agenda. Issues relevant to this milieu include legislative proposals to ban animal use for cosmetic testing, adequacy of the current standard (viz., the Draize Eye Irritancy Test), availability of non-animal methodologies, validation paradigm for new testing models, international harmonization of testing standards and methods, and the regulatory role in product testing and enforcement. The Food and Drug Administration (FDA) feels that enactment of legislation proposed to ban animal use from testing products for safety would pose serious problems from a public health perspective. FDA encourages the development of alternative test methods and is aware that many such tests are in various stages of evolution. At this time, however, none of these tests has been accepted by the scientific community as total replacement to the Draize test. FDA's basic positions on the use of non-animal alternatives are as follows: 1) The use of animal tests by industry to establish the safety of regulated products is necessary to minimize the risks from such products to humans, 2) The Draize eye irritancy test is currently the most valuable and reliable method for evaluating the hazard or safety of a substance introduced into or around the human eye, and 3) No non animal tests are presently available to completely replace the Draize. FDA is actively involved with U.S. and international groups to harmonize protocols for product development, evaluate the current status of non-whole animal methodologies, and standardize testing requirements. The Agency has recently participated in several scientific symposia evaluating the status of non-whole animal methods in toxicity testing. Moreover, FDA representatives are currently scheduled to participate in international meetings and workshops planned for the immediate future addressing several issues in product safety determination. PMID- 1301786 TI - In vivo assessment of corneal stromal toxicity by tandem scanning confocal microscopy. AB - Epithelial wound closure following superficial corneal abrasions precipitates a complex series of cellular changes in the stroma. Transmission electron microscopy and light microscopy have demonstrated that keratocytes in the anterior stroma show prominent cytoplasmic process and granularity within an hour after this injury. Cell degeneration follows rapidly, with almost complete depletion of these keratocytes by 6-12 hours. Regeneration then occurs by 24-48 hours. These findings were confirmed in-vivo by tandem-scanning confocal light microscopy in rabbits. The optical sectioning capability of this instrument allowed us to demonstrate the three-dimensional array of fibroblast process, their subsequent condensation, and loss by sequential examinations on the same animals. Cell shrinkage and other fixation artifacts common in corneal histological sections were avoided by this technique. Using this method, we investigated the corneal cytotoxicity of an antimitotic agent, mitomycin-C and a muscarinic antagonist, atropine sulphate. Mitomycin-C, an antimetabolite used in pterygium treatment, led to irreversible keratocyte depletion even after four days of observation. However, cellular reaction to the wound were attenuated by atropine sulphate suggesting that it may be useful as a novel inhibitor of fibroblast proliferation. PMID- 1301787 TI - In vivo MRI and fluorescence studies on the ocular lens. AB - During the past two decades progress in biophysical technology has made it possible to monitor aging and pre-cataractous as well as cataractous changes in the ocular lens in vivo as well as in vitro. Because they are non-invasive these techniques can be performed in vivo and utilized as screening methods to detect and predict eventual lens opacification, and they should also provide increasingly important information to help clarify the cataractogenic process. Three such biophysical approaches can now be employed in vivo; these include lens fluorescence, light scattering measurements and magnetic resonance imaging (MRI) T2 analyses (1-27). We have utilized two of these methods (fluorescence spectroscopy and MRI measurements of lens water [T2] phases) to delineate normal age-related and pre-cataractous changes in a series of human subjects and in patients with early lens opacities. The parameters employed for these studies were based on data accumulated from in vitro experiments on human lenses and in vivo and in vitro data from animal experiments (2, 6-8, 18, 19, 22, 25-27). PMID- 1301789 TI - Comparative investigations on the cataractogenic effect of a triazin-derivative in albino and pigmented rats: II. Effects documented by Scheimpflug photography. AB - A Triazin-derivative from a group of industrial chemicals was found to cause cataracts in albino rats during a subchronic toxicity study. To get more insight into this effect, a study was designed with 20 albino (Wistar) and 40 pigmented (black-hooded FB 30) rats using different dosages of the test compound. In a 3 months study period, all rats were photographed with a Scheimpflug camera TOPCON SL-45 3 times, at a baseline examination, prior to any treatment, in the middle and at the end of the study period, prior to sacrifice. The black-and-white film (Kodak T-Max 400R) was standardly developed and evaluated with a Joyce-Loebl microdensitometer in 3 regions of the lens, the capsule, the cortex and the nucleus. The density data from the second and third examination clearly demonstrate that cataract development in the albino rats takes place in the cortical region, whereas in the pigmented rats it takes place in the cortical and partly in the nuclear region. In addition, one albino and two pigmented animals of the groups investigated developed bilateral mature cataracts. Differences in cataract morphology between albino and pigmented rats are presented by Eiben and Wegener (1). The results underline the importance of toxicity testings in pigmented rats, they evidence that the data derived solely from albino animals can be misleading. PMID- 1301788 TI - Quantification of blood-aqueous barrier function using laser flare measurement and fluorophotometry--a comparative study. AB - Fluorophotometry allows calculation of the permeability coefficient k(a) of the blood-aqueous barrier to fluoresceine after i.v. dye application; aqueous flare can be graded objectively by laser flare measurement and permits in vivo estimation of over-all protein concentration in the aqueous humor. To evaluate a formal relationship between both procedures we performed laser flare measurements on 40 eyes (clinically ranged from healthy to mild uveitis) before and during fluorophotometry. Laser flare count [mec-1] raises exponentially (r = 0.8; p = 0.05) with an increasing permeability coefficient to fluoresceine k(a) [10(-4)min 1]. Laser flare count during the fluorophotometry procedure is not increased (p = 0.05) compared to the prescan. Reproducability was 14% +/- 7.5% for laser flare measurements and 13% +/- 5% for fluorophotometry. Malfunction of the blood aqueous barrier possibly increases the permeability to molecules of high molecular weight not proportional to that of hydrophilic particles of low molecular weight. The exponential regression between the data achieved with both procedures suggests that fluorophotometry is more sensitive in detecting early changes in blood aqueous barrier function whereas laser flare detection could be appropriate in more severe cases of barrier dysfunction. PMID- 1301790 TI - Overview of the corneal toxicity of surgical solutions and drugs: and clinical concepts in corneal edema. AB - Surgical solutions and drugs are important in ocular surgery. These include irrigating solutions, viscoelastic substances, mydriatics and miotics, and a growing number of other agents designed to enhance intraocular surgery and its outcome. Potential for damage to the corneal endothelium and other tissues is related to the chemical composition, pH, and osmolality of the irrigating solutions that bathe tissues. Quality balanced salt solutions (BSS) are usually safe for use as an intraocular solution in patients with normal corneal endothelium. If prolonged irrigation times are expected, or the patient already has decompensated endothelium, i.e., primary or secondary endotheliopathy, the use of a "complete" BSS solution is indicated to minimize damage. Intraocular sulfite-containing epinephrine may cause severe corneal edema and should be avoided, or if used, be well diluted. Sulfite-free epinephrine solution is now available and does not cause the endothelial toxicity that one may see with sulfite-containing epinephrine solutions. Current formulations of acetylcholine and carbachol used as miotics in surgery have been evaluated in humans and caution is recommended in using acetylcholine solutions intracamerally in patients with already decompensated endothelium. Chondroitin sulfate, hydroxypropyl methylcellulose, and sodium hyaluronate are non-toxic to animal endothelial cells under conditions analogous to cataract extraction in humans but can be toxic to endothelium if there is continued contact with endothelium for hours. Chondroitin sulfate has been shown to have more of a protective effect in mechanical pseudophakos trauma probably because of its cohesiveness and tendency to coat the endothelium. Viscoelastics cause a significant rise in intraocular pressure of > 30 mm Hg in 3-10% of patients. Very high intraocular pressures are often seen postoperatively after viscoelastic use surgically in patients who preoperatively have a history of ocular hypertension or glaucoma. PMID- 1301791 TI - The role of viscoelastics, cannulas, and irrigating solution additives in post cataract surgery corneal edema: a brief review. AB - Corneal clarity is dependent upon maintenance of the corneal endothelial barrier and pump. Mechanical trauma is usually considered to be the most significant factor in corneal endothelial damage during cataract surgery resulting in postoperative corneal edema. However, corneal decompensation out of proportion to the degree of trauma seen during surgery does occur. These cases of unexpected corneal edema can often be traced to unrecognized preoperative endothelial dysfunction or to toxicity of intraocular medications used during surgery. This paper reviews the role of viscoelastics in reducing surgical trauma, their toxicity, and the risks of toxicity inherent in the use of re-usable cannulas and irrigating solution additives. Disposable cannulas should be used whenever possible. The use of re-usable cannulas with viscoelastics is highly likely to result in toxic residues being introduced onto the eye, and must be avoided. Irrigating solution additives should be tested with in-vitro human donor cornea perfusions prior to clinical use. PMID- 1301792 TI - Cytotoxicity of ophthalmic preservatives on human corneal epithelium. AB - Because the corneal epithelium invariably encounters the full concentration of the preservative that is contained in multi-dose topical ophthalmic preparations, we investigated the cytotoxicity of several of these agents by using a sensitive model of human corneal epithelial cells in vitro. Primary cultures of epithelial cells were prepared from freshly enucleated globes. At confluence, all experimental cultures received a single dose of preservative at the concentration present in marketed formulations. The serum in the culture medium simulated the possible neutralizing effect of proteins present in the tear film in vivo. The cells were observed continuously by phase-contrast microscopy and time-lapse videomicrography for 24 hrs. Benzalkonium chloride at a concentration of 0.01% and chlorobutanol at 0.5% caused immediate cell retraction, as well as cessation of normal cytokinesis, cell movement, and mitotic activity; the epithelial cells degenerated within 2 hrs and 8 hrs, respectively. Cultures treated with chlorobutanol developed conspicuous blebs on the cell surface after 3 to 5 hrs of exposure. Thimerosal (0.001%) caused cell retraction, cessation of mitotic activity, and total cell destruction within 9 hrs. Sorbic acid (0.1% and 0.2%) greatly reduced cell movement and suppressed mitotic activity, but no cell death occurred. At concentrations of 50 ppm and 30 ppm, H2O2 instantaneously caused a marked retraction of the cells, followed by cessation of cytokinesis, cell movement, and mitosis. Retraction and death of the epithelial cells occurred within 12-24 hrs after exposure to 1 ppm H2O2 in serum-free medium. Polyquaternium ammonium chloride (0.001%) and polyaminopropyl biguanide (0.00005%) had no discernible effects on cytokinetic movement or on the mitotic activity of the epithelial cells. We relate our findings in vitro to those reported in vivo and discuss the mechanism of cytotoxicity of the various preservatives. PMID- 1301793 TI - Assessing the biostability of intraocular lenses. AB - This manuscript represents an attempt to evaluate the methods used to assess the biostability of IOLs, in particular their leaching characteristics, the effects of laser pitting, their tensile strength and the effects of UV irradiation on long term implantation of IOLs. The literature relating to these topics during the last two decades has been reviewed and experimental study protocols are presented. PMID- 1301794 TI - Cytogenetic assays for genotoxic agents. AB - The induction of genetic damage has clear and dramatic implications for human health, with teratogenic, mutagenic, cataractogenic and carcinogenic consequences resulting from cellular chromosomal alterations in appropriate tissues. When analysing the potential of an agent to initiate genetic damage or in evaluating possible incumbent genomic damage a variety of complementary assays may be employed. These apply to cells in vitro, to in vivo assessments involving small mammals and most importantly to derived human cells and tissues including those of ocular origin. Cytogenetic assays have the important advantage that they enumerate damage at the level of the individual cell. Assays involving the examination of chromosomal aberrations at mitosis, of cells prior to mitosis using the technique of premature chromosome condensation, of micronuclei in post mitotic cells and of sister chromatid exchanges will be described. The development of human chromosome specific probes and fluorescent in situ hybridisation (FISH) techniques combine the resolution of molecular biology with classical cytogenetics in a powerful approach to defining genomic change and its consequences. These techniques and assays can be further augmented by in situ cytometry such that overall a number of parameters can be quantified involving cellular kinetics, clastogen and/or aneugen definition and ultimately the establishment of dose response relationships. A rational basis for avoidance or control, for intervention or for defining probable cause of the role of genotoxicants in the development of human disease can then be established. PMID- 1301795 TI - Ocular side effects of accutane therapy. AB - The recent interest in treating acne with one of the retinoid drugs has been accompanied by a wide variety of ocular side effects involving the eyelids, cornea, lens, optic nerve and retina. In one group of patients being evaluated for possible efficacy of a retinoic acid analogue in treating psoriasis, several patients complained of difficulty driving at night due to decreased dark adaptation which we were able to document. Fortunately, most of the above side effects tend to disappear within months after the drug is discontinued. However, we have recently seen two cases of dry eye syndrome associated with Accutane therapy that have persisted for more than two years. In addition, scattered reports have appeared regarding cataracts in young patients (teens to early 40's) which developed during, and/or after Accutane treatment. We have examined lens matter derived from two such patients who had extracapsular cataract extractions. Their lens proteins showed an elevation in UV absorptivity (between 330-390 nm) compared with matched control material (derived from Eye Bank specimens) and HPLC analyses demonstrated an abnormal peak in their profiles which was similar to one present in control samples incubated with retinoic acid and was not present in lens protein samples derived from cataracts not associated with Accutance therapy. These observations demonstrate that some of the Accutane induced ocular side affects are not reversible when the drug is stopped, and patients on such therapy should be carefully monitored. PMID- 1301796 TI - Ocular toxicity of subconjunctival gentamicin. AB - The subconjunctival injection of commercial gentamicin, given either as a single dose or as repeated injections, caused a hyperemic conjunctival response. Simultaneously there was a toxic myopathy induced in the extraocular muscles. The overall response, followed with light microscopy, occurred as a focal infiltrate of polymorphonuclear leukocytes with progression over a few days to a mononuclear cell infiltrate that accompanied fiber degeneration. Injections of each ingredient of commercial gentamicin individually showed that only gentamicin caused the muscle response; methylparaben, EDTA, and sodium bisulfite were without effect. The pH of the solution was eliminated as a contributing factor as was osmolarity of the injection. Increasing recognition is being given to post operative complications caused by the prophylactic subconjunctival injection of gentamicin following cataract, and other intraocular surgery. The present data offer a mechanistic explanation for many of these toxic findings. PMID- 1301798 TI - Ocular toxicity of prednisone in pediatric patients with inflammatory bowel disease. AB - We performed ocular examinations on 58 corticosteroid-treated pediatric patients with inflammatory bowel disease (IBD) and on 58 age-matched controls. Posterior subcapsular cataracts (PSC) were detected in 12 of the 58 treated patients (20.7%) and in none of the controls. The difference in mean intraocular pressure (IOP) between the treated patients (15.89 +/- 4.11 mm Hg) and control subjects (13.63 +/- 2.35 mm Hg) was significant statistically (P < 0.001). Twenty-one patients (36.2%) were characterized as "IOP responders" (IOP > or = 20 mm Hg, change in IOP > or = 6 mm Hg between visits, or a difference in IOP > or = 6 mm Hg between the two eyes). Formation of PSC was not correlated significantly (P > 0.05) with the total dose of prednisone, duration of treatment, average daily dose, or number of days on high doses (> or = 25 mg). Raised IOP was correlated (P = 0.005) only with average daily dose (12.4 +/- 10.9 mg/day; range, 0-47 mg/day) 30 days before examination. When the dose of corticosteroid was reduced to < 10 mg/day, 2 patients manifested regression of PSC, and 12 IOP responders showed a decrease in IOP to within 2 SD of the mean control IOP. Only 3 of the 58 treated patients (5.2%) manifested both PSC and raised IOP. A significant inverse correlation (P = 0.02) was established between IOP at first examination and formation of PSC. We propose that the mechanisms for steroid-induced lens opacities and raised IOP do not share the same genetic basis. Because 52% of these children developed either PSC or raised IOP with prednisone therapy, we advocate careful ophthalmologic monitoring of pediatric patients receiving corticosteroids for IBD or any other condition. PMID- 1301797 TI - Cataract in renal transplantation recipients with combination ciclosporin treatment. AB - Post surgical cataracts induced by corticosteroids as immunosuppressive agents were investigated in recipients undergoing triple therapy with ciclosporin and the results were compared with those who had therapy without ciclosporin administration. The subjects of the triple therapy group were 54 cases with a mean age of 31.7 years. The mean observation period was 25 months. The incidence of posterior subcapsular cataract was 77.8%. 7.9% of them developed progressed cataract. Early cataractous changes were noticed within one post-operative year in half of the cases. 3 out of 22 cases that were followed up over three years showed progressed cataractous changes. The total doses of methylprednisolone during the period of the first post-transplant year in recipients with Grades I or II and over Grade III were 7.7 +/- 1.9g and 9.8 +/- 3.6g, respectively. They were significantly higher than those in the conventional therapy group. However, a 2 to 3 g reduction in the total dose of steroids during the first year had no influence on cataract occurrence. PMID- 1301799 TI - Effect of intravitreal injection of norfloxacin on the retina in pigmented rabbits. AB - The effect of an intravitreal injection of norfloxacin on the retina was evaluated by in-vivo electroretinogram (ERG) and histological examination in pigmented rabbits. The intraocular pharmacokinetics after an intravitreal injection of norfloxacin were also investigated. An intravitreal injection of 50 micrograms norfloxacin produced no significant change in the ERG. An injection of 500 micrograms norfloxacin decreased the amplitude of the oscillatory potentials, and delayed their peak latencies 3 hours after the injection, but these changes recovered within 7 days. A marked suppression of the c-wave was noted in one pigmented rabbit. Neither 50 micrograms nor 500 micrograms norfloxacin caused any apparent changes in the visual evoked potential and in the retinal histology 7 days after the injection. The intraocular pharmacokinetic study showed that the concentration of norfloxacin in the choroid-retina was almost the same level as that in the vitreous body 3 hours after the injection. However, the former was higher than the latter 7 days after the injection, suggesting the persistency of norfloxacin in the choroid-retina. An intravitreal injection of 50 micrograms norfloxacin could be used without retinal toxicity. A high dose-intravitreal use of norfloxacin needs careful attention with respects to its persistency in the pigmented ocular tissues. PMID- 1301800 TI - Effect of Gingko biloba extract (EGb 761) on chloroquine induced retinal alterations. AB - Electroretinography was used to investigate the preventive action of Ginkgo biloba extract (EGb 761) in experimental chloroquine-induced retinopathy in rats. EGb 761 contains flavones and anthocyanosides known for their oxygenated radical scavenging properties. Chronic administration of chloroquine (20 days) caused an overall lengthening of the duration of the ERG b-wave, together with delayed peaking. These anomalies became more marked with increased duration of treatment. In rats treated simultaneously with chloroquine and EGb 761 no such modification of the electroretinogram (ERG) was observed. These results suggest that retinal toxicity may be related to a localized inflammation releasing oxygenated free radicals and/or PAF. EGb 761 may thus afford a useful preventive treatment for chloroquine-induced retinopathy, and generally for xenobiotic retinotoxicities. PMID- 1301801 TI - Inhibition of vincristine-induced retinal impairments by a specific PAF antagonist. AB - The alkaloid vincristine is widely used for its anti-leukemic and anti-tumor activity. However, the drug also displays considerable toxicity, particularly for the retina. Indeed, vincristine has been shown to induce alteration of photoreceptor outer segments in animals and impairment of scotopic vision in man. This type of retinopathy is an inflammatory disease in which PAF may be implicated and for which specific PAF antagonist may have a therapeutic role. Thus, we measured the effects of a new hetrapezine derived PAF antagonist, BN 50730, on a vincristine-induced retinopathy in the rat. Retinal impairments were established by recording several parameters of the electroretinogram (ERG) obtained from isolated retina. Our results indicate that, first, the increase in PIII duration induced by vincristine is significantly reduced by BN 50730 administration and, second, the decrease in the value of the PIII/b wave ratio caused by vincristine is partially inhibited by treatment with BN 50730. These experiments suggest that PAF is implicated in vincristine retinopathy and demonstrate the therapeutic effect of a specific antagonist of the mediator. PMID- 1301803 TI - A new approach to drug penetration study. AB - To investigate the route of drug penetration into the eye and drug distribution patterns in the lens, the distribution of aldose reductase inhibitor (AL-04114) in the lens was measured in short term bovine lens organ cultures and topical administration to rabbit eyes. A micro lens sectioning technique was applied to determine drug localization within the lens. Freshly enucleated bovine lenses were incubated with different concentrations of an ARI (AL-04114)-containing medium for 3 hours. For the in vivo study, 40 microliters of 0.3% AL-04114 (ophthalmic solution) were administered into the cul de sacs of rabbits 3 times at 3 hour intervals. After the incubation and final instillation, the lenses were divided into an equatorial ring and several layered sections. Drug concentration was measured by a reversed-phase HPLC system. The drug concentration was highest within the layer of the posterior shallow cortex > equator > anterior shallow cortex. No drug penetration was observed in the anterior/posterior deeper cortex or nucleus in vitro. The in vivo experiment revealed drug penetration in the equator and anterior shallow cortex, but not in any other lens layers. Drug penetration was detected within the serum and aqueous humor, but not in the vitreous. PMID- 1301802 TI - Intraocular penetration and effect on the retina of fluconazole. AB - The intraocular concentration of fluconazole was measured in nonvitrectomized and vitrectomized eyes after an intravenous administration of 5 or 25 mg/kg fluconazole in albino rabbits. Respective fluconazole concentrations in the aqueous, vitreous and serum 1 hour after administration were 2.87, 1.72 and 4.60 micrograms/ml at 5 mg/kg administration, and 14.93, 7.05 and 20.63 micrograms/ml at 25 mg/kg administration, indicating high and dose-dependent intraocular penetration of fluconazole. Intraocular penetration of intravenously administered fluconazole was moderately, not very much, enhanced by vitrectomy. The in-vitro electroretinogram (ERG) remained unchanged after perfusion with 20 micrograms/ml of fluconazole. The in-vivo ERG and the visual evoked potential was unchanged after the daily administration of 25 mg/kg fluconazole for 8 days. The toxicity of fluconazole on the retina would be low and within safety limits so far as it is used at clinical dosage. Fluconazole may have a place in the treatment of fungal ocular infections. PMID- 1301804 TI - [The biological aspects of botfly invasions in reindeer]. AB - Field and laboratory studies established the development time of all the phases of Oedemagena tarandi and Cephenemyia trompe in different climatic zones of their habitat. The phenological and ecological features of O. tarandi and C. trompe in the aforesaid zones were identified which are the basis for scientifically grounded prophylactic measures. Data on potential and actual fecundity make it possible to calculate their reproduction potential and to forecast the invasion intensity of the reindeer in the next season. PMID- 1301805 TI - [The action on brain functions in white rats of the immunostimulant Freund's complete adjuvant]. AB - The effect of immunostimulator--Freund's adjuvant complete on the nociception and learning of white rats using food-obtaining and avoidance of electric shock techniques has been studied. It has been shown that the adjuvant in doses for active immunization causes itself the expressed changes in animal behaviour. The adjuvant's injections significantly increases the learning ability of animals both with negative and positive reinforcement as compared with control one. The changes in pain severity is marked only for dose 0.2 ml. The nonspecific action of adjuvant should be taken into account in researches which use the active immunisation method. PMID- 1301806 TI - [Problematic situations of intercultural misunderstanding in social services]. AB - This article discusses research on the difficulties of practising social work in a multicultural and multiethnic context. The research is based on critical incidents that were experienced by 40 social workers in "the most ethnic" public social service centres of the Montreal region in 1990-1992. The most significant culture shocks that occurred between workers of a developed Western-type society and clients from developing, non-Western societies relate to a different notion of the role of social services, to different methods et educating children, to unequal relationship between men and women, to a different notion of family and to a different notion of physical and mental health. The authors emphasize that a better understanding of these shocks and an effort to identify and analyze these sensitive zones of intercultural encounter can have a definite impact on the practice and training of social workers. PMID- 1301807 TI - [Ethnicity and insanity: the many faces of abnormality]. AB - This article suggests that the notion of madness varies with the social context, the dominating values of each cultural community and the position given to agents and social workers in the field and in the hierarchy of knowledge. As an interplay of representations and cognitive strategies, madness can be considered as a "symptom" of the "normative" and "reductive" biases of each era, but also as a revealing trait of the sensibility of each culture toward certain dimensions of unusual experiences. Following a review of the magical, prophetic, theological, moral, pathological and analytical versions of madness, the author concludes by emphasizing the necessity of always taking into consideration the cultural standpoint that characterizes the experience of madness as much as it does its study. PMID- 1301809 TI - [A pathogenic manpower program: the program for foreign domestics]. AB - Every year, a special federal program arranges for the arrival of about 12,000 educated women to Canada to work several years in private homes as housekeepers. However, in order to meet the needs of the employer and the Canadian economy, these women are denied their fundamental freedoms and are deliberately kept in a precarious situation material and psychologically and with respect to their status. Because it exposes these female workers to such factors of instability and to the negative effects of key experiences, this program carries the seed of mental illness. PMID- 1301808 TI - [Ethnic relations and identity-based tensions in a multicultural context]. AB - Since the beginning of the 80s, Montreal's population of non French--and non English-speaking inhabitants has increased rapidly, especially in schools (estimates show that by the year 2000, this segment will represent about 50% of students). In addition, this population of diverse origins is composed of only a minority of Europeans; Caribbeans and Orientals make up the vast majority of immigrants that have settled in Montreal over the last decade. How does this unique mix of cultural backgrounds impact on the perception that these youth from multiethnic neighbourhoods have of their own culture and social relations? This is the basic issue that the authors have attempted to solve in the course of their research. The authors focused particularly on the identity-based tensions that stem from interaction between youth and the strategies they develop to overcome these tensions. PMID- 1301810 TI - [Training is not always a quick solution]. AB - This article examines the training strategy developed in 1990 by the Table de concertation des Organismes de Montreal au service des Refugies, which was designed for social workers employed by non governmental organizations who were offering new arrivals a variety of support services to help them establish themselves and integrate. The term "new arrivals" includes immigrants and refugees, and takes into account the fact that members of communities that have been established in Quebec for a longer period of time may still be using these services. The social workers of these organizations work on a permanent, temporary, internship or volunteer basis. Their work covers a wide variety of areas: assistance in finding lodging and furniture, held in meeting the requirements of immigration services, information on various public services (schools, health and social services, etc.) and referrals to appropriate specialized services. In short, the intervention of community social workers is characterized by versatility and diversity. In his article, the author uses the term "intervenant" to describe these social workers. The training strategy under study aims to facilitate communication and contacts between protagonists that do not necessarily share the same values, nor the same world vision. PMID- 1301811 TI - [Parental stress in mothers of preschool children: validation and Quebec norms for the Parental Stress Inventory]. AB - The authors examine the metrological qualities of a French version of the Parenting Stress Index (Abidin, 1983; Loyd and Abidin, 1985) based on a sampling of 122 Quebec mothers with a preschool child. Results show that the Parental Stress Inventory presents internal consistency indices that are equivalent to those obtained in the U.S. sampling. However, the samplings differ on seven out of 13 subscales, as well as concerning the scores obtained for the child's realm and the overall stress, Quebec mothers show higher scores. The factorial analysis of the subscales supports the existence of a hierarchical structure composed of a general factor of parental stress and two specific factors: the realm of the child and the realm of the parent. The score relative to the realm of the parent varies according to the socioeconomic level and the marital status of the mother. The mother's age is negatively correlated with the score of the child's realm. The child's aggressiveness/hyperactivity level, as perceived by the teacher in a class situation, is positively correlated with the score of the subscale Difficulty to accept the child's characteristics and the subscale Distraction and hyperactivity of the child. The authors present benchmarks that were developed in order to take into account the noted differences between the Quebec and U.S. samplings. PMID- 1301813 TI - [Future perspectives, factors in the mental health of aged persons]. AB - During individual interviews, 708 people between the ages of 65 and 90 expressed a wide variety of personal goals and aspirations through sentences they were asked to complete. The distribution of answers in temporal categories provides an index of the broadening of future perspectives (PF). The values of that index were put in relation with subjective assessments that can be looked upon as clues to mental health. Results confirm the hypothesis of a positive relation between PF and perception of health (0.27), meaning of life (0.29), living satisfaction (0.30) and perception of having personal control (0.18). However, PF does not appear to be connected with the person's attitude toward death. These results seem to indicate that PF represents a factor of mental health and "healthy aging". Consequently, they justify the relevance of developing interventions that aim to strengthen this "personal resource". PMID- 1301812 TI - [Support provided by third parties and the reaction of close female caregivers in the care of elderly persons with loss of autonomy]. AB - This article is about the relation between, on the one hand, support provided by third parties and, on the other, the burden and the depression experienced by the main female supporters who care for the elderly suffering from physical or cognitive problems. The authors examine the hypothesis that social support is not homogeneous across the board and that the different types of support are likely to have different effects on elders with adverse reactions to the caring process. Data originates from a study that was conducted in the Montreal area in 1990 with 159 female supporters living with an elder requiring care who requested support services from formal and informal networks. Hierarchical regression analyses show that the variables in connection with care dispensed by the network play a limited role in attempting to explain the depression and burden levels. Furthermore, these analyses confirm the hypothesis of the variables' narrow range of influence. PMID- 1301814 TI - [Reactions of social workers in a mental health day center and the avoidance of institutionalization of individual defense mechanisms]. AB - The author attempts to describe the different strengths that emerge from the role of the supervisor (clinic) in a community organization in relation to two aspects: the maintaining of the defining characteristics of the notion of "alternative" and the dynamic understanding of the social worker-user relationship. After a review of how a day centre operates, the author describes the individual and collective "defense mechanisms" that are used by social workers to alleviate the impact of the user's baffling behaviour on their personality. The author follows by showing that failure to use these defense mechanisms can lead to burnout for the social worker, while certain forms of collective defense mechanisms can prompt this alternative care system to institutionalize itself from within. PMID- 1301815 TI - [Analysis of the medical and psychosocial evaluations required by the new public curator law]. AB - The new Public Curator Act systematically requires medical and psychosocial evaluations. In confronting the letter and the spirit of the law to its regulations and operating procedures (and inversely), this article outlines the various tasks that will fall under the responsibility of health and social service professionals. Following a brief presentation of the law, the authors describe how the role of these professionals is limited to evaluations for the purpose of conducting expert appraisements, a matter which raises a great deal of concern. In addition, the two key notions of "inaptitude" and "need" are discussed in their legal sense, along with their consequences from the medical evaluation and psychosocial standpoints. The latter in particular will be analyzed regarding implementation difficulties. The authors conclude with a general commentary that is likely to give meaning to that simple and sometimes routine gesture consisting of "completing a form". PMID- 1301816 TI - [Mental health and ethnocultural communities: social marginalization from existential precariousness]. PMID- 1301817 TI - [Health center for the Association for Victims of Repression in Exile]. PMID- 1301819 TI - [AIDS and traditions in Burkina Faso]. PMID- 1301818 TI - [Objectives, pertinence and methodology of the Quebec mental health survey of youths from 6 to 14 years old]. PMID- 1301820 TI - [Mental health of migrants: analysis of the social and longitudinal context]. AB - The mental health of migrants is affected by many factors that stem from premigratory experiences as well as adaptation conditions of the host nation. The interaction of these two types of factors are however set in time: certain periods are characterized by relative stability, while others are marked by unexpected disruptions which tend to make migration appear as a never-ending process. An individual's age upon arrival in a new country is also an important factor: adolescents must meet many different types of demands, while the elderly no longer have the personal resources to assimilate a new culture. The author points out that adaptation takes place in a family system where the fortune of each member impacts on that of others in the family. In this article, the author discusses prevention by taking into consideration certain issues raised by scientific literature. PMID- 1301822 TI - [Insanity without frontiers]. PMID- 1301821 TI - [Political migration, economic migration: a systemic lecture on the process of integration by migrant families]. AB - In this paper, the author aims to establish links between the family, the socio cultural system and migration, a process which represents a significant relocation of the space in which one or several living systems evolve. The concepts of family and migration are meshed in order to present explicative models of the operation and the adaptation guidelines of families undergoing migration. The author bases his study on his role as an observer and human being who is striving to make sense of his environment and create a dialogue around a theme that deeply disturbed him in his individual, family and social phenomenology. PMID- 1301823 TI - [Theoretical and methodological principles of ethnopsychiatry: the example of migrant children and their families]. AB - The realm of ethnopsychiatry also includes the cultural dimension of chaos (and the ways of overcoming this chaos) and the analysis of psychic foundations. This original method deals with the "complementarity" between psychoanalysis and anthropology. In doing so, it establishes a new link between the clinician and the patient, between traditional therapies and modern treatments, between the outside (culture) and the inside (psyche). This approach can be successfully applied to the context of migration, particularly to the child who is torn between the culture of his parents and the culture of the host nation. PMID- 1301824 TI - [The clinician's cultural identity and its role in the relation with the patient]. AB - From an interactionist point of view, the cultural life history of the clinician is as important as that of the patient. In present day Europe, migratory upheavals have requested adjustments at all levels. There are foreign patients, yet professionals are themselves also culturally diversified. Affected by the migration stress, they too are submitted to its effects. The author proposes that the patient/clinician relationship be revisited in the light of the interpretative-reflexive interaction model between informant and ethnographer in the anthropological fieldwork. PMID- 1301825 TI - How much of the brain must die in brain death? PMID- 1301826 TI - Healing and killing, harming and not harming: physician participation in euthanasia and capital punishment. PMID- 1301827 TI - Care perspective and its application to clinical practice. PMID- 1301828 TI - Imagining ethics: literature and the practice of ethics. PMID- 1301829 TI - Perinatal technology: answers and questions. PMID- 1301830 TI - Sedating women with mental retardation for routine gynecologic examination: an ethical analysis. PMID- 1301831 TI - Brain death and the termination of life support: case and analysis. PMID- 1301832 TI - Against caring. PMID- 1301833 TI - Legal trends in bioethics. PMID- 1301834 TI - Competence as accountability. PMID- 1301835 TI - Quantifying the value of human life for cost accounting of safeguards: clarifying formulas applied to the clozapine controversy. AB - Using CPMS as an example, this article has developed mathematical formulations to compare the value of lives saved against the cost of medical safeguards. By a logical comparison of benefit and cost converted to the same units of currency, the article explores three important questions relating to the CPMS example. These mathematical formulations serve to quantify the decision-making process in a logical manner, and might serve as a useful example for clinical and public policy decisions. PMID- 1301836 TI - Spousal understanding of patient quality of life: implications for surrogate decisions. PMID- 1301837 TI - The development of a clinical ethics consultation service in a community hospital. PMID- 1301838 TI - Being on time for appointments. PMID- 1301839 TI - Decision making in the NICU: the question of medical futility. PMID- 1301841 TI - Implementation of the Patient Self-Determination Act (PSDA) PMID- 1301840 TI - What should be done when a proxy is reluctant to carry out the wishes of an incompetent patient? PMID- 1301842 TI - Doctors must not kill. PMID- 1301843 TI - Doctors must not kill. PMID- 1301844 TI - [Prospective study of traditional Chinese medicine and Western medicine in acute abdomen]. PMID- 1301845 TI - [Immune function and abdominal surgery in blood stasis syndrome in patients with gastrointestinal diseases]. AB - 52 Patients with Blood Stasis Syndrome (BSS) in abdominal surgical diseases were divided into 3 types according to their symptoms, signs and natures of diseases. Peripheral blood T lymphocyte subsets of these BSS patients and 12 healthy persons were studied with Flow Cytometry and monoclonal antibodies. The immunoglobulins and complements of these cases were also studied. There were no difference in T cell subsets, immunoglobulins and complements between Qizhi-BSS group and normal control. The Shire-BSS group showed that CD8 cell, IgG, IgM, and C1, C3c were increased. These results showed that the immune response increased in this type of BSS patients. In the Qixu-BSS group, the CD3 was nearly normal, and the CD4+, CD4+/CD8+ ratio, and CD16+ were statistically decreased. However, the CD8+ cells markedly increased, the IgG, IgM and IgD were also lowered significantly in this type. The marked morphologic abnormal changes in ultrastructures of T lymphocyte were found in 6 patients with Qixu-BSS group. These results showed that the Qixu type of Blood Stasis Syndrome patients were in the immuno-suppressive status. PMID- 1301846 TI - [Efficacy of replenishing kidney therapy on biological activity of serum luteinizing hormone in aged subjects]. AB - There have been many research reports about changes of aging of hypothalamus pituitary-gonad axis, but no satisfactory explanation on the constancy or elevation of serum gonadotropin level in aging. However it is important in revealing the mechanism for aging gonadal axis of and its function in regulating gonadal gland as well as the senility delaying process with therapy for replenishing the Kidney. Serum luteinizing hormone (LH) of 48 men at various age was investigated with Rat Interstitial Cell Testosterone Assay (RICT) and Radioimmunoassay (RIA) techniques. The serum level of RICT (B-LH) tended to decrease and the B-LH/I-LH ratio was significantly lower (P < 0.01) than that in aged group (> or = 50 years old) in comparing with the young group (< or = 44 years old). The result suggested that the biological activity of LH decreased with age and the stimulative function of pituitary to testes also diminished. With the recipe "Bao Chun Pill" in replenishing the Kidney for 3 months, the biological activity was markedly enhanced (P < 0.05), the serum testosterone (T) was also escalated (P < 0.01). Both of them in treated group were higher than those in control group (P < 0.05). The study and our previous works showed that the therapy for replenishing the Kidney could improve the function of gonadal axis in aging subjects at all levels of hypothalamus, pituitary, gonad. PMID- 1301847 TI - [Clinical study in treating qi-deficiency and blood-stasis syndrome of angina pectoris with qi xue granule]. AB - 55 cases of Qi-deficiency and Blood-Stasis syndrome of coronary heart disease (CHD) and angina pectoris (AP) were divided randomly into two groups. Qi Xue granule (QXG) was administered to 30 cases of treated group, while compound Salvia tablet (CST) was administered to 25 cases of control group. Besides, both group were also given one placebo tablet or granule so as to eliminate the patient's psychological effects. RESULTS: (1) Effects on clinical symptoms: Total effective rate for AP: 90% in QXG group, marked effective rate and effective rate for ischemic ECG changes were 30% and 46.6% respectively. All of these were better than that of CST group significantly (P < 0.05). Besides, QXG group could alleviate symptoms including asthenia. (2) Effects on submaximal paddle work load test: QXG group could prolong the capacity of exercise (from 336.2 +/- 34.7 to 437.5 +/- 43.8 seconds, P < 0.05), magnify the work load (from 73 +/- 7.18 to 94 +/- 8.5 W, P < 0.05) and elevate the ST segment (from 0.218 +/- 0.03 to 0.176 +/- 0.03 mV) significantly in comparison with CST group, which had little change only. (3) Effects on plasma TXB2, 6-keto-PGF1 alpha (6 Kp) level and ration of TXB2/6Kp in 10 normal subjects were 165 +/- 12.1 pg/ml, 142.6 +/- 17.4 pg/ml and 1.16 +/- 0.19 pg/ml respectively, while in 36 cases AP were 390.6 +/- 14.3, 106.0 +/- 7.9 and 3.67 +/- 0.85 pg/ml respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301848 TI - [Effect of yiqi huoxue therapy on blood coagulation process in vivo]. AB - YiQi HuoXue (YQHX) therapy is one of the most widely used treatments to deal with the coronary heart disease (CHD). This paper stressed on study the effects of YQHX therapy on blood coagulation process in vivo. The effects of several TCM preparations on CHD patients were observed by thromboelastography (TEG), prothrombin time, etc. After giving various preparations 20ml intravenously, the results of TEG showed that the values of r, k, c, 1 were decreased and ma increased by QiXue injection, the differences of k and ma were significant; while no significant change by Shen Qi injection and the k value was significantly reduced by DanShen injection. The results of prothrombin time with QiXue injection showed distinct dose-dependent effects, it shortened with 20ml and significantly lengthened with 40ml. This results suggested that there was complicated effects of different YQHX preparations as well as of different dosages. PMID- 1301849 TI - [Effects of Astragalus membranaceus and Tripterygium hypoglancum on natural killer cell activity of peripheral blood mononuclear in systemic lupus erythematosus]. AB - Natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) from 28 patients with systemic lupus erythematosus (SLE) was measured using enzyme release assay. The SLE patients had significantly decreased NK activity in comparing with normal controls. The levels of NK activity correlated with disease activity. Pre-incubation of PBMC separately with Astragalus membranaceus and Tripterygium hypoglaucum or with their mixture considerably stimulated NK cytotoxicity both in SLE patients and healthy donors. The extent of enhancement was dose-dependent and relevant to pre-incubation periods. The release of a soluble natural killer cytotoxic factor (NKCF) by peripheral blood mononuclear cells was tested by cytotoxicity assay induced in K562 cells. Natural killer cytotoxic factor release was significantly lower in SLE patients than in controls. The levels of natural killer cytotoxic factor were correlated well with NK activities, but correlated negatively with clinical activity. Pre-incubated supernatants from peripheral blood mononuclear cells with above-mentioned agents caused much higher percentage of lysis on K562 targets than that of without pre incubation. PMID- 1301850 TI - [Clinical and experimental study of Ligusticum wallichii and aspirin in the treatment of transient ischemic attack]. AB - This paper reports the results of the treatment of 158 cases with transient ischemic attack (TIA). They were randomly divided into Ligusticum wallichii group (111 cases) and Aspirin group (47 cases). The results showed that the total effective rate in Ligusticum wallichii group and in Aspirin group were 89.2% and 61.7% respectively. The effect of former on the treatment of TIA was superior to latter, and the difference between them was significant (P < 0.01). Experimental study showed that Ligusticum wallichii has the effects of increasing cerebral blood flow, accelerating the velocity of blood flow, dilating the spastic artery and decreasing peripheral arterial resistance. Both of them has the functions of decreasing the levels of thromboxane B2(TXB2), beta-thromboglobulin (beta-TG) and platelet factor IV (PF4) in plasma and increasing the concentration of 6-keto prostaglandin F1 alpha (6 keto-PGF1 alpha) in plasma, the effect of Ligusticum wallichii was significantly better than Aspirin (P < 0.05). PMID- 1301852 TI - [Connotation and academic value of Dun Huang traditional Chinese medicine and pharmacology]. PMID- 1301851 TI - [Experimental study of modified yu ping feng powder on antibacterial adhesion of tracheal mucosa in mice model of chronic bronchitis]. AB - In order to observe the influence of modified Yu Ping Feng San (MYPFS) on bacterial adhesion of tracheal mucosa, four experiments of bacterial adhesion in pneumatic tract were conducted, in which mice of chronic bronchitis model (CBM) induced by SO2 stimulation and another health control group breathed in aerosol contained Pseudomonas aeruginosa under the same condition were observed. The results showed that, with scanning electron microscopy, ultrastructural lesions on tracheal mucosa surface and adhesive bacterial number in CBM administrated MYPFS were far less than that in CBM without MYPFS (P < 0.001), and quantitative culture of Pseudomonas aeruginosa with tracheal tissue homogenate was also markedly reduced. However, the tracheal mucosa of healthy control animals were intact, the adhesive bacteria were not found. It is suggested that bacterial adhesion was closely related to the injury of tracheal-mucosa, and MYPFS could play a role of anti-bacterial adhesion through the protection of tracheal mucosa epithelium or reduction of pneumatic tract injury. These were quite in accordance with the theories of traditional Chinese medicine in "strengthening body resistance to eliminate the pathogenic factor", so that they provided experimental evidence for TCM tonics to prevent and treat infection of respiratory tract. PMID- 1301853 TI - [Diagnostic criteria and therapeutic efficacy of traditional Chinese medicine and Western medicine in simple obesity]. PMID- 1301854 TI - [Research of cellular membrane fluidity and traditional Chinese medicine]. PMID- 1301855 TI - [Traditional Chinese medicine combined with Western medicine in chronic myelitis]. PMID- 1301856 TI - Shaping practice through research. PMID- 1301857 TI - Patterns of nausea during first trimester of pregnancy. AB - This descriptive study examined pregnancy nausea to determine whether nausea occurred more frequently during the morning hours than during other times of day and if certain patterns of nausea exist. The 19 women who participated in the study kept daily diaries of their nausea experiences over a 7-day period, noting the time of occurrence. Nausea was reported most frequently during waking hours, ranging from 40.3% of the time between 7 p.m. and 10 p.m. and 43.9% between 3 p.m. and 6 p.m. Most nausea reported by subjects was mild, although 18% of the nausea reported between 11 p.m. and 2 a.m. was severe. Four patterns of nausea were identified: morning peak, evening peak, bimodal, and all day. Whereas some women displayed fairly consistent daily patterns of nausea, others reported variations in the occurrence or severity of nausea over the 7-day study period. PMID- 1301858 TI - Setting an agenda for clinical nursing research in long-term care. AB - Twenty nurse experts participated in a four-round Delphi study to identify topics requiring clinical nursing research in long-term care. The Delphi strategy elaborated 265 items grouped in seven categories, with 73 items under the category of clinical practice. After four rounds, participants ranked the top rated 50 items overall in serial importance. Nineteen of the 50 items were clinical practice items. A weighted rank than identified the top 10 items requiring investigation. Of these 10, the item deemed most important was patient centered outcomes, an item subsuming all clinical nursing research. PMID- 1301859 TI - Barriers to implementing a continence program in nursing homes. AB - Urinary incontinence is a problem for over 50% of nursing home residents, but it can respond to toileting programs. Nursing home staff, however, do not always follow the toileting schedules. Dimensional analysis of research logs that were kept during the implementation of an individualized toileting regimen for incontinent residents revealed several barriers to staff adherence to the protocol. System barriers included staffing shortages and limited licensed staff reinforcement. Individual barriers included conflicting beliefs and goals and difficulty organizing care routines. Conclusions suggest that implementation of toileting programs by nursing assistants could be improved with adequate and stable staffing, incentives for staff, and assistance with organizing work load. Establishing continence as the standard of care in nursing homes is a crucial element to the success of any toileting program. More research is needed to better understand how staff perceive, organize, and prioritize their care. PMID- 1301860 TI - Bedside nursing research. A new category of research? AB - A new category of clinical nursing research, labeled "bedside nursing research," is proposed and described in this article. Justification for this research category is based on its particular characteristics, such as its narrow focus on direct care procedures that have well-defined parameters and the patient outcomes of those procedures. Findings from this type of research have high clinical relevance and can directly influence nursing practice at the study site. PMID- 1301861 TI - Development of a predictive model for postoperative pulmonary complications after cholecystectomy. AB - The purpose of this study was to develop a model to predict the occurrence of a postoperative pulmonary complication (PPC) following cholecystectomy. Seventeen potential risk factors were extracted from the literature by identifying and ranking those most frequently referenced. The study included only those risk factors available to the nurse in the preoperative, intraoperative, and immediate postoperative setting. Three institutions were used for data collection, and data were collected by a retrospective chart review of 300 randomly chosen subjects from a population of 720. Of the 300 subjects, 37 were omitted due to exclusion criteria. A PPC was present in 54 of the remaining 263 subjects (20.5%). Of the original 17 risk factors, 10 were included in model development. The 54 subjects with a PPC and 54 subjects without a PPC (randomly chosen from the remaining 209) were used to determine which combination of risk factors best predicted subject classification (PPC or no PPC). The direct entry discriminant function that provided the highest percentage of correct classification (PPC, no PPC) consisted of five variables: sex, age, smoking history, duration of anesthesia, and nasogastric tube. The resulting equation correctly classified 75% of the cases. PMID- 1301862 TI - The importance of nonverbal communication during the preanesthesia period. AB - This article discusses the phenomenon of nonverbal communication as evidenced between preoperative patients and the nurses attending them. Ten such patients and the nursing group assigned to them were directly observed for frequency of nonverbal interaction during the period immediately preceding surgery. Patients' nonverbal expressions of tension, fear, anxiety, and so on were noted, videotaped, and then analyzed according to three categories of interaction: positive, neutral, and negative. Of 2,173 registered nonverbal interactions, 65.1% (1,416) were rated as negative, a finding that should alert nurses to the need to identify patients' manifestations of anxiety so as to provide assurance and a sense of courage preceding surgery. Positive means of communicating nonverbally are discussed. PMID- 1301863 TI - Liver transplantation. AB - Nationwide, healthcare professionals are more involved with liver transplantation. Although providing a new lease on life is very rewarding within itself, it can also be stressful for all involved. Through a better understanding of the actual procedure, healthcare professionals can alleviate some of their own stress as well as understand the anxiety of the recipient. PMID- 1301864 TI - Political and legal aspects of transplantation. AB - Each year, the number of people in this country waiting for life-saving transplantation grows, spurred on by increased survival rates. This article discusses the multiple factors influencing transplantation and the selection of recipients, including political, legal, and economic aspects. PMID- 1301865 TI - Case study: single lung transplantation for alpha 1-antitrypsin deficiency. AB - alpha 1-Antitrypsin deficiency predisposes individuals to emphysematous pulmonary changes. Single lung transplantation (SLTX) represents a promising, viable option for the management of alpha 1-antitrypsin deficiency/chronic obstructive pulmonary disease (COPD). The purpose of this case study is to discuss the relationship between alpha 1-antitrypsin deficiency. COPD, and SLTX, and the role of the perioperative nurse. PMID- 1301866 TI - Management and administration of the operating room during transplantation. AB - Organ transplantation has proliferated since the 1980s. Perioperative nurses are involved in the transplant process from donor to recipient, from procurement to replacement, and in administrating the success of this surgical miracle. PMID- 1301867 TI - Ethical considerations in organ transplantation. AB - The transplantation of organs has a historical background that parallels the emergence of general bioethics, rather than the traditional authoritarian paternalism of medical ethics. Some ethical and moral issues brought forth by the transplantation technology are the determination of death, allocation of scarce resources, donor and recipient selection, and research status. PMID- 1301868 TI - Case study: infant transplantation: a change of heart. AB - The majority of infant heart transplants are for the correction of hypoplastic left heart syndrome (HLHS). This article will describe the preoperative, intraoperative, and postoperative care for perioperative and pediatric intensive care areas implemented for HLHS infant heart transplantation at Medical Center Hospital, San Antonio, TX. The surgical procedure is given. Dimensions of psychosocial care and education of the parents are briefly described. PMID- 1301869 TI - Multiple organ retrieval: impact on staff and institutions. AB - Perioperative nurses, along with other nurses, and health care institutions, are affected directly and indirectly by the present day process of multiple organ retrieval from a declared brain dead donor. The recognition of potential stress and impact situations in the retrieval process may assist in the planning of effective interventions to enable optimal organ retrievals. PMID- 1301870 TI - Future trends in transplantation. AB - With over 15,000 solid organ transplants performed in the United States last year, it is exciting to follow trends in this field. The United Network for Organ Sharing is carefully studying the availability of organs and new methods to enhance organ donation. In the forefront at this time are new antirejection medications being tested throughout the United States. In the basic science and immunology arena are many studies on graft tolerance, whereby organs are accepted by the body with minimal or no immunosuppression. The real answers to many transplantation questions are still being answered through the efforts of ongoing research. PMID- 1301871 TI - Assistive personnel in the perioperative setting: changing the paradigm. PMID- 1301872 TI - The financial management of laser therapy. AB - The development of a financially viable laser program within any health care organization requires detailed resource analysis and planning of each phase. After implementation, administration must constantly monitor all costs associated with care delivery, as well as the reimbursement for services and revenue generated. PMID- 1301873 TI - Marketing a laser program. AB - The objective of a marketing program is to enhance knowledge and perceived desirability of a laser service, thereby improving profitability. Among the 15 tools that make up an effective marketing program are researching the market, identifying an appropriate niche, developing a marketing plan, using publications and advertising, and generating public relations. PMID- 1301874 TI - The regulatory arena of laser technology. AB - The regulatory arena of laser technology can be a very simple or a very complex issue. It is simple if one looks to the only true "regulation" of lasers, ie, the Food and Drug Administration, which has an involved Code of Federal Regulations for the manufacturers of lasers and related technology. It is complex if one looks at all the other recommended guidelines or standards of practice for lasers presented by various organizations. The interpretation and implementation of any of these is an individual responsibility. PMID- 1301875 TI - Staffing a laser program. AB - The setting of laser use influences the identification of laser safety officer selection, education, and responsibilities. These are influenced by American National Standards Institute criteria and the quality management plan. PMID- 1301876 TI - Laser education: current standards and recommendations. AB - Laser technology has made a significant impact on the nursing profession. Technology challenges traditional practices, and presents an array of new clinical therapies and associated hazards for both patients and medical personnel. Educational opportunities must be objectively evaluated if consumers are to obtain credible, valid, and effective training that will prepare them to comply with current standards and recommended practices. PMID- 1301877 TI - Conducting laser research. AB - Nurses today are sometimes reluctant to get involved with research due to their lack of involvement or experience. This article simplifies the research process by comparing its steps with the familiar steps of the nursing process. Laser technology offers nurses the challenge of an ever-changing arena in which research projects can be easily identified and conducted. PMID- 1301879 TI - Ambulatory surgery in 1952. PMID- 1301878 TI - Perioperative nursing care of the patient experiencing laser surgery. AB - Perioperative nursing care for patients undergoing laser procedures must reflect the six-step nursing process of assessment, diagnosis, outcome identification, planning, implementation, and evaluation. Recommended practices, guidelines, and institutional policies and procedures offer additional guidance for an optimal level of practice by nurses involved with patients having laser procedures. PMID- 1301880 TI - Ambulatory surgery: clinical issues. Introduction. PMID- 1301881 TI - Arthroscopic knee surgery. AB - Arthroscopy of the knee has become a high-volume procedure for ambulatory surgery centers. As technology advances, these procedures will become more complicated. Perioperative nurses are challenged to stay abreast of advancing technology. This article discusses the perioperative care of the client having arthroscopic knee surgery. PMID- 1301882 TI - Intraoperative advances: laparoscopic cholecystectomy. AB - The introduction of laparoscopic cholecystectomy in general surgery is an exciting technology because of the success that has been produced using the procedure. The noninvasive surgical approach was introduced at a time when medicine needed a new advancement in the plan of care for the surgical patient. The less invasive procedure, shorter hospital stay, and faster recovery are just a few of the reasons why laparoscopic cholecystectomy is a procedure that is now gaining popularity in the ambulatory surgery setting. PMID- 1301883 TI - Client education in the ambulatory surgery setting. AB - The recent increase in the number of clients having ambulatory surgery has had an enormous impact on how nurses provide client education. This article discusses the purpose of client education, provides examples of teaching strategies used in the ambulatory surgery setting, and describes the benefits of postoperative follow-up calls. Examples of preoperative and discharge instruction forms are provided. PMID- 1301884 TI - Developing a competency-based education program for nurse-monitored sedation. AB - Because of technological innovations and changes in the methods of health care delivery in the ambulatory setting, a new role for the perioperative nurse has emerged, that of monitoring patients who receive intravenous (IV)-conscious sedation during surgery and other invasive procedures. This article describes how to develop a competency-based education program for an ambulatory surgery center advocating the role of both a circulating nurse and monitoring nurse for the care of patients receiving IV-conscious sedation. PMID- 1301885 TI - The Patient Self-Determination Act. AB - The Patient Self-determination Act (PSDA) of 1990 mandates that individuals receiving medical care must be given written information about their rights under state law to make decisions about medical care, including the right to accept or refuse medical or surgical treatment. The law applies to all health care facilities providing services and receiving federal reimbursement including nursing homes, home health agencies, clinics, and hospitals. This article discusses the impact of this legislation on ambulatory surgery facilities. PMID- 1301886 TI - Documentation: incorporating the nursing process. AB - The nursing process is a formalized, systematic approach to providing and documenting nursing care and is an integral component of any documentation. This article discusses the nursing process and its relation to ambulatory surgery documentation, as well as the impact of standards of health care organizations on the documentation process for the perioperative patient in the ambulatory surgery setting. PMID- 1301887 TI - Ambulatory surgery: recovery to discharge. AB - In the ambulatory surgery setting, the registered nurse plays a key role in preparing the client for discharge. This article discusses how the nurse can use the nursing process to determine when the client is ready for discharge from the ambulatory facility. PMID- 1301888 TI - Twenty-three hour recovery: observation versus hospitalization. AB - In the wake of the rapidly changing health care delivery environment, it is becoming essential to health care organizations that unique, innovative methods of managing resources be implemented. Further, such developments must be achieved within the confines of those requirements and revisions occurring within the reimbursement structures of Medicare and Medicaid as well as other third-party payors in keeping with the delivery of quality patient care. The evaluation of patients in an outpatient environment for a period of time before a final decision regarding disposition is made creates the "observation concept." This article discusses the significance of 23-hour observation units for ambulatory surgery patients. PMID- 1301889 TI - Alexia without agraphia: potential for model assisted therapy. PMID- 1301891 TI - Testing the tried: replicating sentence-processing therapy for agrammatic Broca's aphasia. PMID- 1301890 TI - Facilitating written production. PMID- 1301892 TI - Training and generalization of expressive syntax in nonfluent aphasia. AB - Generalization of treatment effects remains a consistent goal of clinicians who treat aphasic adults. Specifically, various types of stimulus/response generalization designs are available, depending on the level of generalization desired. We have reviewed training matrices designed to elicit gestural subject plus-verb targets and treatment studies designed to answer more global questions regarding treatment efficacy. As Kearns (1989) so eloquently states, "clinical accountability cannot, in fact, be fully achieved without documentation of communication skills trained in the clinic generalized to other settings and situations." Although the studies cited and data reviewed in this article did not meet this standard specifically, an attempt was made to provide a brief prelude to the data now emerging in the aphasiology literature. Additionally, with an increasing data base in the literature specific to generalization, more efficacious treatment paradigms will be made available. Clinicians treating aphasic adults thus should have the opportunity to choose the treatments shown to be most effective for a specific type and severity of aphasia. PMID- 1301893 TI - Improving listening comprehension of narratives. PMID- 1301894 TI - Methodology for discourse management in the treatment of aphasia. PMID- 1301895 TI - Efficacy of aphasia treatment: what are the real issues? PMID- 1301896 TI - Innovative instructional programs for students with language or behavioral disorders. AB - We described creative and innovative language programs for students with LLD and BD, or both. There are three models of learning that have had considerable impact on how language services have been designed and executed for these two populations of students. Our principal argument is that there is a fourth approach or model based on empowerment. We presented the premises and principles of the empowerment model and described two programs using empowerment as the foundation for the provision of communication and language services. Language and communication programs grounded in an empowerment model offer greater possibilities for students to acquire the discourses necessary for successful participation in the culture of school, as well as the cultures in which they participate outside of school. Discovering strengths and competencies across a wide spectrum of learning affords students opportunities for developing self knowledge based in capability and adeptness rather than in deficiency and impairment. The emergence, unfolding, and eventual maturation of these competencies and capabilities are critical not only to those students who discover them, but also to the future of all of us. PMID- 1301897 TI - A proactive model for treating communication disorders in children and adolescents with traumatic brain injury. AB - This proactive approach to assessment and intervention focuses both on looking ahead to determine problems the student with TBI is likely to encounter as a result of cognitive-communicative impairments, and on developing solutions to those problems. Intervention places the family and other important people in the student's life at the center of the treatment process. Family members, teachers, peers, and coworkers can be incorporated into the intervention program. Strategies and techniques can be implemented within the home, school, community, and work setting. To do so, professionals must be committed to working closely with others to develop collaborative relationships. PMID- 1301898 TI - Service delivery in augmentative communication. PMID- 1301899 TI - Achieving cultural sensitivity: a process, not a product. PMID- 1301900 TI - Assessment of parent communicative behaviors: an overview. PMID- 1301901 TI - Group caregiver language checklist. AB - Because young children with language disabilities frequently are placed in group care settings, there is a need to make judgments concerning the language environment of those settings. The GCLC is offered as one procedure for assessment of the language environment provided by the caregiver(s) in a group setting. The assessment provides information that may assist in matching the environment to a particular child's needs and may provide a basis for assisting caregivers in improving the language environment and addressing a child's needs. The authors welcome comments from the readers. PMID- 1301902 TI - Family-centered early intervention: an opportunity for creative practice in speech-language pathology. AB - Services for developmentally delayed children from birth to age three consider the family first. Eligibility for services is determined through a multidisciplinary assessment. Once a child qualifies for service, a multidisciplinary team that includes the family develops an IFSP. The SLP may serve as the service coordinator for the plan or as a team member. The plans must contain specific information that includes documentation of current status and major outcomes for the coming year. An SLP may find that contributing effectively to an IFSP requires new competencies. First, the SLP will need to learn to function in the family-centered, multidisciplinary process of early intervention. Second, the SLP may need to develop creative models to deliver effective service. SLPs can contribute valuable information to the IFSP by finding ways to activate daily life routines to promote a child's communication skills. SLPs can explore the child's life-space, including routines and partners, as a source of contexts for treatment. SLPs also can explore partner communication strategies, note their effects on the child's communication experiences, and recommend additional strategies for treatment. The case study illustrated an individual, home-based intervention program (Gillette, 1989; Lombardino and Magnan, 1983). Other service delivery models can include classroom-based approaches (Wilcox, Kouri, and Caswell, 1991); group parent training approaches (Weistuch, Lewis, and Sullivan, 1991; Cheseldine and McConkey, 1979); and video-assisted approaches (McConkey, 1988; Johnson and Harrison, 1990; Gillette, in press). Many SLPs may find that the process of early intervention with the birth-to-three population offers unique opportunities for practice in their profession. To function effectively in this process, the SLP needs communication-based information to promote the child's communication skills within his or her daily life and sensitivity with which to design a plan that considers the family first, yet meets the needs of the child. Although alternative models of delivering speech-language service have been explored, the process of early intervention will continue to require professionals who can creatively match family priorities with the child's intervention needs. PMID- 1301903 TI - General principles of human genetics. PMID- 1301904 TI - Genetics of hearing disorders. PMID- 1301905 TI - Genetics in speech disorders. PMID- 1301906 TI - Craniofacial malformations and their syndromes. An overview for the speech and hearing practitioner. AB - Congenital malformations of the craniofacial region represent an important class of human developmental disorders. Abnormalities of speech and hearing frequently occur in this vast array of conditions. Knowledge of the diagnostic criteria, genetics, and natural history of these conditions is important for audiologists and speech-language pathologists because of their close involvement with the children and families in their care-providing role. Awareness of the important distinction between individuals with isolated defects vs. individuals who have their facial defect as part of a syndrome is important in diagnosis and management. Referral for genetic counseling is always indicated in families who have questions about these issues. The dysmorphologist, genetics professional, and speech-language pathologists are among those who play key roles in the care of persons with these disorders. PMID- 1301907 TI - Identification of genetic influences. PMID- 1301908 TI - Neurogenetic aspects of communication disorders. PMID- 1301909 TI - Genome mapping and sequencing 1992: a meeting report. PMID- 1301910 TI - Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. AB - Plasmid pRSVL persisted and expressed luciferase for at least 19 months in mouse skeletal muscle after intramuscular injection. Other injected plasmids also stably expressed long-term suggesting that any plasmid DNA could stably persist and express in muscle. Plasmid DNA was demonstrated by quantitative PCR in some of the muscle DNA samples for at least 19 months after injection. The methylation pattern of the plasmid DNA remained in its bacterial form indicating that the foreign DNA did not replicate in the muscle cells. The electroporation of total cellular DNA from injected muscles into bacteria indicated that the plasmid DNA was extrachromosomal. Chromosomal integration of plasmid DNA was searched for by electroporating the injected muscle DNA into bacteria after restriction enzyme digestion and ligation. No plasmids containing plasmid/chromosome junctions were observed in over 1800 colonies examined. Lack of integration increases the theoretical safety of this gene transfer technique. Long-term stability of plasmid DNA in muscle indicates that muscle is an attractive target tissue for the introduction of extrachromosomal plasmid or viral DNA for the purpose of gene therapy. PMID- 1301911 TI - A molecular deletion map of the Y chromosome long arm defining X and autosomal homologous regions and the localisation of the HYA locus to the proximal region of the Yq euchromatin. AB - 41 Y-linked DNA probes that detect sequences on the Y chromosome long arm have been used to analyse genomic DNA from a series of 23 patients with deletions of Yq. Southern blot analysis has differentiated 15 distinct breakpoints, which divide Yq into 14 mapping intervals. From the pattern of DNA sequences present in each patient, it has been possible to produce a congruent deletion map, with the exception of two cases which are not compatible with the consensus order. These patients can be explained by the presence of inversion polymorphisms on Yq in the general population or by complex rearrangements induced during the formation of the deleted chromosomes. The distribution of sequences on the Y long arm has defined distinct regions of homology with autosomes, the Y short arm and the long and short arms of the X. A number of the patients have been typed for the presence or absence of H-Y antigen (as determined by the cytotoxic T-cell assay) and it has been possible, from analysis of informative cases, to assign the locus to the proximal region of the Yq euchromatin. PMID- 1301912 TI - Rapid and simultaneous detection of multiple mutations by pooled and multiplex single nucleotide primer extension: application to the study of insulin responsive glucose transporter and insulin receptor mutations in non-insulin dependent diabetes. AB - The application of molecular scanning techniques to the detection of potentially pathogenic mutations in candidate genes in patients with non-insulin-dependent diabetes has revealed a number of molecular variants of uncertain pathophysiologic significance. The determination of the significance of such variants requires large-scale population studies of the prevalence of the mutant in affected and control groups. Herein, we describe two adaptations of the technique of single nucleotide primer extension (SNuPE) which allow the simultaneous examination of large numbers of alleles at multiple loci. The usefulness of these adaptations is illustrated by their application to the simultaneous detection of three point mutations, two in the tyrosine kinase domain of the insulin receptor and one in the insulin-responsive glucose transporter (GLUT4) in a highly insulin-resistant NIDDM population. By pooling genomic or amplified DNA and performing the SNuPE reactions with three primers of different length we could readily examine 300 alleles on a single 20 lane gel. Using pooled SNuPE, we also examined a large British Caucasian control population for the prevalence of GLUT4 Ile383, a variant which has previously been reported only in NIDDM. GLUT4 Ile383 was detected in 2/42 of the highly insulin-resistant NIDDM subjects and 4/240 middle-aged blood donors. Family studies and examination of the expressed mutant transporter will be necessary to establish whether this mutation is of functional significance. Pooled and multiplex SNuPE are powerful techniques with wide applicability to population genetic studies of specific mutations. PMID- 1301913 TI - DNA methylation represses FMR-1 transcription in fragile X syndrome. AB - Fragile X syndrome is the most frequent form of inherited mental retardation and segregates as an X-linked dominant with reduced penetrance. Recently, we have identified the FMR-1 gene at the fragile X locus. Two molecular differences of the FMR-1 gene have been found in fragile X patients: a size increase of an FMR-1 exon containing a CGG repeat and abnormal methylation of a CpG island 250 bp proximal to this repeat. Penetrant fragile X males who exhibit these changes typically show repression of FMR-1 transcription and the presumptive absence of FMR-1 protein is believed to contribute to the fragile X phenotype. It is unclear, however, if either or both molecular differences in FMR-1 gene is responsible for transcriptional silencing. We report here the prenatal diagnosis of a male fetus with fragile X syndrome by utilizing these molecular differences and show that while the expanded CGG-repeat mutation is observed in both the chorionic villi and fetus, the methylation of the CpG island is limited to the fetal DNA (as assessed by BssHII digestion). We further demonstrate that FMR-1 gene expression is repressed in the fetal tissue, as is characteristic of penetrant males, while the undermethylated chorionic villi expressed FMR-1. Since the genetic background of the tissues studied is identical, including the fragile X chromosome, these data indicate that the abnormal methylation of the FMR-1 CpG island is responsible for the absence of FMR-1 transcription and suggests that the methylation may be acquired early in embryogenesis. PMID- 1301914 TI - Minisatellite variant repeat (MVR) mapping: analysis of 'null' repeat units at D1S8. AB - Minisatellite variant repeat mapping by PCR (MVR-PCR) is a new approach to studying variation in human DNA which analyses interspersion patterns of variant repeats within minisatellite arrays. MVR-PCR has been applied to the hypervariable human minisatellite D1S8 which contains two major classes of variant 29bp repeat units designated a-type and t-type. The MVR-PCR assay uses a- or t-type specific primers, together with an amplimer at a fixed site in the DNA flanking the minisatellite, to reveal the interspersion patterns of variant repeats along an allele. Extreme levels of variation are seen both in the internal structures of individual alleles and in the digital code generated from the two superimposed alleles in total genomic DNA. However, occasional repeat units fail to amplify in MVR-PCR, signifying the existence of further repeat sequence variants termed 'null' or O-type repeats. Although not significant in individual identification, correct genotyping of null repeats is important when using MVR digital codes in parentage analysis. We have therefore characterised these null repeats and show that most null repeats share a common variant repeat sequence. We discuss the possible origins of null repeats and their application to paternity testing and the analysis of minisatellite evolution. PMID- 1301915 TI - Autosomal dominant retinitis pigmentosa (adRP): exclusion of a gene from three mapped loci provides evidence for the existence of a fourth locus. AB - Retinitis Pigmentosa (RP) is a group of inherited retinopathies which affect approximately 1 in 4,000 individuals. The disorder can be classified on the basis of inheritance; dominant, recessive and X-linked forms have been well documented. The existence of genetic heterogeneity within autosomal dominant RP (adRP) had been previously demonstrated. As a result of extensive linkage studies in 2 large Irish families and 1 American pedigree three adRP genes have been mapped. adRP genes have been localised to chromosome 3q close to the rod photoreceptor gene, rhodopsin; to chromosome 6p close to another transmembrane photoreceptor gene, peripherin/RDS and to the pericentric region of chromosome 8, although the causative gene in this region has not yet been identified. Here we report the results of a linkage study in a Spanish family, who exhibit an early-onset form of adRP. The adRP gene segregating in this family has been excluded from the three known adRP loci on chromosomes 3q, 6p and 8 using a series of both intragenic microsatellite markers from the rhodopsin and peripherin/RDS genes and markers flanking the three known loci. These results provide definitive evidence for the existence of a fourth adRP locus, further emphasising the genetic heterogeneity that exists within adRP. PMID- 1301916 TI - Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency. AB - The Lesch-Nyhan disease is caused by an almost complete lack of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Partial HPRT-deficiency, associated with less severe phenotype, has also been identified. We have characterized mutations occurring in HPRT cDNA isolated from patients with HPRT deficiency with an emphasis on examining the more unusual partial variants of HPRT-deficiency. HPRT cDNA was amplified by PCR, cloned and analyzed by automated DNA sequence analysis. Twenty-two, unrelated individuals with HPRT deficiency were studied including eight classic Lesch-Nyhan patients and fourteen patients representing the different groups of partial HPRT deficiency. We found a diverse pattern of mutations with point mutations accounting for the majority of abnormal HPRT genes. Nonsense mutations and exon deletions were only found in HPRT cDNA isolated from classic Lesch-Nyhan patients. Mutations associated with partial HPRT-deficiency were frequently located in the amino terminal part of the molecule. A CpG mutational hot spot was identified at the position for Arg-51 in the HPRT protein. Two hyperuricemic patients exhibited unusual splice site mutations: in one this led to the creation of an additional exon in the HPRT gene and in the other part of exon 6 was missing in a subpopulation of the transcripts, producing the effect of a dominant, negative mutation. PMID- 1301917 TI - Four dinucleotide repeat polymorphisms on chromosome 9 (D9S143-146). PMID- 1301918 TI - Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta). PMID- 1301919 TI - A microsatellite polymorphic probe on chromosome 3p: lambda LIB12-2CATT (D3S1244). PMID- 1301920 TI - SSCP polymorphism in the human hepatic triglyceride lipase (LIPC) gene. PMID- 1301921 TI - Dinucleotide repeat polymorphism at the D1S182 locus. PMID- 1301922 TI - Dinucleotide repeat polymorphism at the D19S206 locus. PMID- 1301923 TI - Dinucleotide repeat polymorphism at the D5S253 locus. PMID- 1301924 TI - Myotonic dystrophy: another case of too many repeats? AB - Myotonic dystrophy (DM) is an adult form of muscular dystrophy affecting about 1 in 8,000 individuals in most populations. Although common symptoms include progressive muscle weakness and stiffness, it is characterised by a heterogeneous clinical picture. Despite this variation in both the nature and severity of the symptoms seen in affected individuals, DM is genetically homogeneous, segregating as a single locus on the proximal long arm of human chromosome 19. As the biochemical abnormality underlying the disease was unknown, a reverse genetics (or positional cloning) strategy for identifying the gene responsible was adopted. The resulting collaborative effort culminated in the detection of the molecular mutation event and the gene within which it lies: the expansion of a trinucleotide repeat (CTG) at the 3' end of a gene encoding a member of the cyclic AMP-dependent protein kinase family. This has diagnostic implications since an easy, reliable and predictive test can now be offered to individuals with a family history of DM. These findings are also a prerequisite for further studies concerning the biochemical and physiological aetiology of DM and possible therapeutic strategies. In addition, the striking similarity between findings at the DNA level in DM and those in fragile X syndrome and spinal and bulbar muscular atrophy suggests that the mechanism leading to the increase in copy number of trinucleotide repeats at particular loci may be responsible for a number of other genetic diseases. PMID- 1301925 TI - Genetic basis of galactosemia. AB - Classic galactosemia is an inborn error of galactose metabolism and results from deficiency of the ubiquitously expressed enzyme galactose-1-phosphate uridyltransferase (GALT). Nine missense mutations, three splicing mutations, three GALT protein polymorphisms, and one silent nucleotide substitution have been identified to date. Most of the disease-causing mutations are rare among patients. The most common mutation, Q188R, has a frequency of only one-fourth in the patient population examined. Three classes of disease-causing mutations have been reported: CRM+ missense mutations (the most common class), CRM- missense mutations, and splicing mutations. Thus, galactosemia is heterogeneous at the molecular level, which is noteworthy in light of the well-documented clinical variability observed in this disorder. It has also been shown that eight of nine galactosemia missense mutations occur in evolutionarily well-conserved domains, suggesting that they affect functionally and/or structurally important residues. In contrast, all protein polymorphisms alter variable amino acids which presumably are not important for the enzyme's function. PMID- 1301927 TI - Frequency and distribution of phenylketonuric mutations in Orientals. AB - The frequency and distribution of eight mutations (R111X, IVS4nt-1, Y204C, R243Q, IVS7nt-2, W326X, Y356X, and R413P) in the phenylalanine hydroxylase gene of Orientals in Japan and Korea were examined by allele-specific oligonucleotide hybridization. The mutant alleles comprised 54 and 55% of the phenylketonuria (PKU) chromosomes examined in 36 patients in Japan and 10 patients in Korea, respectively. The spectrum of PKU mutations in Japan was similar to that in China, particularly in northern China, but different from that in Korea. The IVS4nt-1 mutation had a high frequency in Korea and southern China, due to the result of the founder effect and genetic drift. The R413P mutation, which may have originated in the regions surrounding the Baikal, expanded to northern China and Japan. We did not find Caucasian mutations in the Japanese or Korean PKU chromosomes. Thus, PKU mutations occurred after racial divergence between Caucasians and Mongoloids, and there were different founding populations for PKU in the two populations. PMID- 1301926 TI - Two transthyretin variants (TTR Ala-49 and TTR Gln-89) in two Sicilian kindreds with hereditary amyloidosis. AB - We report the biochemical and molecular characterization of two new transthyretin (TTR) variants in two Italian families with hereditary amyloidosis. Both families presented neuropathy and cardiomyopathy but they differ in other clinical features. These TTR variants were previously detected by isoelectric focusing (IEF); one is a neutral TTR variant and the other one is basic. By protein and DNA analysis the neutral variant was found to have a substitution of an alanine for a threonine residue at position 49 (TTR Ala-49) of the polypeptide chain. The basic variant has a glutamine residue replacing glutamate at position 89 (TTR Gln 89). PMID- 1301928 TI - A new intragenic polymorphism detected by the single-strand conformation polymorphism (SSCP) assay in the dystrophin gene. AB - We have employed the single strand conformation polymorphism (SSCP) technique to examine a group of patients with Duchenne or Becker muscular dystrophy who do not contain deletions detectable by multiplex PCR or Southern/cDNA, in an attempt to identify uncommon mutations within the dystrophin gene. In SSCP analysis, a mutated sequence can be detected as a change of mobility in a nondenaturing polyacrylamide gel. During the course of this investigation, we detected and characterized a new polymorphism at the 3' end of intron 16. The G-to-T base change creates a TaqI restriction site which allows for rapid typing of the polymorphism by restriction digestion and electrophoresis of PCR amplified products. Its localization inside the 5' region of the dystrophin gene and its high heterozygosity makes it a useful and easy tool for rapid carrier and prenatal diagnosis. PMID- 1301929 TI - Somatic mutations at CA-repeat loci. AB - We found somatic mutations, detected as novel PCR bands, at three separate polymorphic CA-repeat loci. At one of these loci, analyzed in a three-generation pedigree, a new band generated from the same paternal allele was observed in four of six offspring. The other two children inherited the alternative paternal allele unchanged. Somatic mutations at two additional loci were identified upon subsequent comparison of banding patterns among 25 cancers and their corresponding normal tissues at 15 CA-repeat loci. Since somatic mutations of CA repeats seem to be quite frequent, individuals who are mosaic for CA-repeat alleles at a particular locus probably are not unusual. Hence, the possibility of somatic mutation generating new length alleles at CA-repeat loci should be considered when one compares DNA samples, whether in forensic and paternity testing, loss of heterozygosity studies, or linkage analyses. PMID- 1301930 TI - A comprehensive scanning method for rapid detection of beta-globin gene mutations and polymorphisms. AB - We describe a scanning procedure for the detection of beta-globin gene mutations and the prenatal diagnosis of beta-thalassemias. The method is based on the combined use of PCR and denaturing gradient gel electrophoresis (DGGE) of six amplified fragments encompassing the whole beta-globin coding region and splice junctions, as well as the promoter and 3' untranslated regions. The whole beta globin gene can be rapidly scanned for the presence of deleterious mutations. The proposed diagnostic strategy provides a major improvement over current approaches to beta-globin gene analysis in both research and clinical laboratories, especially those which analyse DNA samples from individuals belonging to various ethnic or population groups. The use of this procedure has enabled us to detect six novel sequence changes in the beta-globin gene, including two deleterious mutations and four polymorphisms. PMID- 1301931 TI - Polymorphic variation within "conserved" sequences at the 3' end of the human RDS gene which results in amino acid substitutions. AB - The human RDS gene, previously mapped to chromosome 6p, encodes a protein found in the outer disc membrane of the photoreceptor cells of the retina. The cDNA sequence of the human gene shows 85% identity with the bovine peripherin gene and the rds (retinal degeneration slow) genes from mouse and rat. Mutations in the RDS gene have recently been implicated in autosomal dominant retinitis pigmentosa (adRP) in some families. Here we present evidence that the third exon of this gene is subject to polymorphic variation in humans. The three sequence alterations described in this paper give rise to amino acid substitutions. However, as these missense mutations also occur in the normal population they are not implicated as causing adRP. Interestingly such sequence variation is not found within other species examined including mouse and bovine. These intragenic polymorphisms will be of future potential value in studies to locate further disease causing mutations in adRP patients in the RDS gene. PMID- 1301932 TI - Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A. AB - Mutations leading to hemophilia A by substitution of amino acids in coagulation factor VIII may provide important clues to the structure and function of this large and enigmatic protein. To efficiently find missense mutations, hemophiliacs with mild and moderately severe forms of the disease were surveyed. DNA samples from affected individuals were assayed for mutations by denaturing gradient gel electrophoresis following DNA amplification of target regions, which included all coding regions except for that of the dispensable B domain. Missense mutations were observed in 20 of the 34 patients examined, with identical mutations found in five pairs of patients. All mutations were found in the repetitive A and C domains. By aligning these domains in factor VIII with homologous domains in factor V, ceruloplasmin, and the mouse milk fat globule membrane protein, it was determined that most mutations change amino acids in areas of strong sequence conservation. Three additional mutations were detected, including a point mutation in an intron, a stop codon mutation, and a silent base change. Ten of the 18 different mutations discovered in this patient population are reported here for the first time. PMID- 1301933 TI - Rapid preparation of genomic DNA from dried blood and saliva spots for polymerase chain reaction. PMID- 1301934 TI - Replication errors may contribute to the generation of large deletions and duplications in the dystrophin gene. AB - Frequent recurrent mutations of the human dystrophin gene lead to Duchenne and Becker muscular dystrophies. Although the approximately 2.5 Mb size of the gene may form a large target for mutations it is not clear to date which mechanisms promote the observed high frequency of spontaneous mutants (1 in 10,000 X chromosomes) of which a high percentage (> 70%) are gross structural aberrations (deletions/duplications). In order to gain insight into possible molecular mechanisms we have cloned and sequenced the deletion junction fragments from two unrelated Duchenne patients. Our data, together with a short review on other cases from the literature, present evidence that errors of DNA replication may contribute to the generation of submicroscopic chromosome rearrangements. PMID- 1301935 TI - A splice junction mutation in intron 2 of the carbonic anhydrase II gene of osteopetrosis patients from Arabic countries. AB - Clinical manifestations in patients with carbonic anhydrase (CA) II deficiency include osteopetrosis, renal tubular acidosis, and cerebral calcification. Of the 39 reported cases of the carbonic anhydrase II deficiency syndrome, 72% were patients from North African and Middle Eastern countries, most, if not all, of whom were of Arabic descent. We have analyzed DNAs from members of six unrelated Arabic kindreds and found five to be homozygous and one heterozygous for a novel splice junction (donor site) mutation at the 5' end of intron 2. These findings suggest that a common "Arabic" mutation may be the predominant cause of CA II deficiency in this region. The mutation introduces a new Sau3A1 restriction site which allows polymerase chain reaction (PCR)-based diagnosis of this mutation that should be useful in diagnosis, carrier detection, and prenatal diagnosis. The presence of mental retardation and relative infrequency of skeletal fractures distinguish the clinical course of the patients with the Arabic mutation from those of the American and Belgian patients with the His 107-->Tyr mutation. PMID- 1301936 TI - A 15-bp deletion in exon 5 of the ornithine aminotransferase (OAT) locus associated with gyrate atrophy. AB - Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive disorder in which a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) leads to progressive blindness. Previously, we and others have reported a number of missense mutations and splice defects in the OAT gene associated with GA. In the present case, through sequencing of the PCR amplified cDNA products, we have detected a novel 15-bp deletion within exon 5 of the OAT gene which retains the original reading frame. The deleted PCR product is the only one produced from the patient's mRNA, while mRNA from the patient's mother yields both deleted and normal length PCR products. The alternate, apparently nonexpressing OAT allele in this patient was inherited from the father, who displays only the normal length PCR product. The codon at the deletion joint remains unaltered, predicting the loss of the pentapeptide Tyr-Thr-Val-Lys-Gly without any other amino acid change. The breakpoints are adjacent to or within two copies of a 4-bp direct repeat, which may have implications for the mechanism of deletion. PMID- 1301937 TI - Molecular basis of hexosaminidase A deficiency and pseudodeficiency in the Berks County Pennsylvania Dutch. AB - Following the birth of two infants with Tay-Sachs disease (TSD), a non-Jewish, Pennsylvania Dutch kindred was screened for TSD carriers using the biochemical assay. A high frequency of individuals who appeared to be TSD heterozygotes was detected (Kelly et al., 1975). Clinical and biochemical evidence suggested that the increased carrier frequency was due to at least two altered alleles for the hexosaminidase A alpha-subunit. We now report two mutant alleles in this Pennsylvania Dutch kindred, and one polymorphism. One allele, reported originally in a French TSD patient (Akli et al., 1991), is a GT-->AT transition at the donor splice-site of intron 9. The second, a C-->T transition at nucleotide 739 (Arg247Trp), has been shown by Triggs-Raine et al. (1992) to be a clinically benign "pseudodeficient" allele associated with reduced enzyme activity against artificial substrate. Finally, a polymorphism [G-->A (759)], which leaves valine at codon 253 unchanged, is described. PMID- 1301938 TI - A mutation common in non-Jewish Tay-Sachs disease: frequency and RNA studies. AB - Tay-Sachs disease (TSD) is an autosomal recessive genetic disorder resulting from mutation of the HEXA gene encoding the alpha-subunit of the lysosomal enzyme, beta-N-acetylhexosaminidase A (Hex A). We have discovered that a Tay-Sachs mutation, IVS-9 + 1 G-->A, first detected by Akli et al. (Genomics 11:124-134, 1991), is a common disease allele in non-Jewish Caucasians (10/58 alleles examined). A PCR-based diagnostic test, which detects an NlaIII site generated by the mutation, revealed a frequency among enzyme-defined carriers of 9/64 (14%). Most of those carrying the allele trace their origins to the United Kingdom, Ireland, or Western Europe. It was not identified among 12 Black American TSD alleles or in any of 18 Ashkenazi Jewish, enzyme-defined carriers who did not carry any of the mutations common to this population. No normally spliced RNA was detected in PCR products generated from reverse transcription of RNA carrying the IVS-9 mutation. Instead, the low levels of mRNA from this allele were comprised of aberrant species resulting from the use of either of two cryptic donor sites, one truncating exon 9 and the other within IVS-9, spliced to exon 10. Numerous additional splice products were detected, most involving skipping of one or more surrounding exons. Together with a recently identified allele responsible for Hex A pseudodeficiency (Triggs-Raine et al. Am J Hum Genet, 1992), these two alleles accounted for almost 50% (29/64) of TSD or carrier alleles ascertained by enzyme screening tests in non-Jewish Caucasians. PMID- 1301939 TI - Human hepatic lipase mutations and polymorphisms. AB - Human hepatic lipase (HL) is a 477 residue glycoprotein that hydrolyzes triglycerides from plasma lipoproteins. Familial HL deficiency is a rare recessive disorder that is characterized by premature atherosclerosis and abnormal circulating lipoproteins. While studying the HL gene from the world's index family with HL deficiency, we identified four coding sequence variants of HL, one in each of exons 4, 5, 6, and 8. In this report we present the genetic basis for two new HL gene variants, one in each of exons 3 and 5. All six HL DNA variants are single base pair changes. Two variants (at codons 133 and 202) are diallelic DNA polymorphisms that are silent at the amino acid level. One variant (V73M) is an allele that defines an uncommon HL isoprotein. One variant (N193S) has two alleles of approximately equal frequency in the population that specify two common HL isoproteins. Two variants (S267F and T383M) are rare mutations found to date only in HL deficient subjects and their relatives. Of the six HL variants described to date, only S267F and T383M are associated with hyperlipidemia. PMID- 1301940 TI - Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method. AB - To investigate the molecular basis of familial hypercholesterolemia (FH) in France, we applied the single strand conformation polymorphism (SSCP) method to the promoter region and the 18 exons of the low density lipoprotein receptor (LDLR) gene. Seven probands, 4 heterozygotes, 2 compound heterozygotes, and 1 homozygote, belonging to FH families were tested. In all cases, previous genetic analysis and/or LDL receptor fibroblast assay had shown that the disease was due to defects in the LDLR gene. Out of the nine mutations expected, one nonsense mutation in exon 2 and six missense mutations were identified in exons 3, 6, 8, 11, and 15. Two of the latter were found in exon 6. In each family, cosegregation of the base substitution and the disease was observed. Ninety-five control subjects were screened for the presence of the six missense mutations. None was detected, implying that the mutations identified are deleterious. Our results indicate that the SSCP analysis of amplified genomic DNA fragments can be successfully used to rapidly screen mutation containing exons in large genes. Furthermore, all these mutations are newly described and demonstrate heterogeneity of LDLR gene mutations responsible for FH in the French population, as in other reported Caucasian populations. PMID- 1301941 TI - alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype. AB - Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive genetic disease caused by a deficiency of the glycosidase alpha-L-iduronidase which is required for the lysosomal degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. Patients with MPS-I store forms of these partially degraded glycosaminoglycans in their lysosomes. MPS-I patients present with a wide range of clinical phenotypes, which makes prognostic predictions and genetic counselling difficult, therefore impeding the selection and evaluation of patients undergoing experimental therapy, such as bone marrow transplantation. We report the presence of two mutations, one that introduces a stop codon at position 70 (Q70X), and the other that alters the proline at position 533 to an arginine (P533R) in the 653 amino acid alpha-L-iduronidase protein. These mutations were originally detected by chemical cleavage and then by direct PCR sequencing. Allele specific oligonucleotides were used to detect the mutations in a group of 73 MPS-I patients and Q70X was found to account for 15% of all MPS-I alleles and P533R for 3% of MPS-I alleles. Both mutations are associated with an extremely severe clinical phenotype in homozygotes. MPS-I patients heterozygous for either mutation may have a wide range of clinical phenotypes. We have now described three mutations, W402X (Scott et al., 1992c), Q70X, and P533R totalling 53% of MPS-I alleles which together define 28% of MPS-I genotypes. PMID- 1301942 TI - A defective splice site at the phenylalanine hydroxylase gene in phenylketonuria and benign hyperphenylalaninemia among Palestinian Arabs. AB - Phenylketonuria (PKU) and benign hyperphenylalaninemia (HPA) result from different combinations of mutations at the locus for phenylalanine hydroxylase (PAH). While some of these mutations show widespread ethnic distribution, others are unique to specific communities. We report here the first point mutation common among Palestinian Arabs. The mutation (IVS2nt1) involves a dinucleotide substitution (Gg-->Aa) at the donor splice site of intron 2 of the PAH gene and abolishes a recognition site of the restriction enzyme MnlI. IVS2nt1 is associated with two PAH polymorphic haplotypes, 7 and 42. Homozygotes for this mutation are affected with severe, classical PKU. Compound heterozygotes carrying the IVS2nt1 allele and one of several other yet unknown mutations show different degrees of benign HPA. PMID- 1301943 TI - A 22-bp deletion in the phenylalanine hydroxylase gene causing phenylketonuria in an Arab family. PMID- 1301944 TI - Illegitimate transcription: its use in the study of inherited disease. AB - In 1988, by using the powerful and accurate cDNA/PCR technique, it was demonstrated that there are very low levels of dystrophin mRNA in a variety of non-muscle tissues, including cultured fibroblasts and lymphoblastoid cell lines. The phenomenon was also shown for a number of other tissue-specific genes, including beta-globin, factors VIIIc and IX, anti-Mullerian hormone, L-pyruvate kinase, retinal blue pigment, phenylalanine hydroxylase. The level of transcript in inappropriate cells is exceedingly low, perhaps one mRNA per 100-1000 cells. This low-level ubiquitous transcription of tissue-specific genes was called "illegitimate" or "ectopic" transcription, and has been proven to occur for 17 gene transcripts to date. The mechanism and biological significance of illegitimate transcription are still obscure, but, since illegitimate transcripts exhibit the same pathology as legitimate transcripts, they have been useful tool in the study of already 9 inherited diseases. This strategy will be applied widely for diseases where samples from the appropriate tissue for study is difficult to obtain, or where an mRNA is easier or more informative to study than a genomic DNA (as for large genes, or where alternative splicing is involved). PMID- 1301945 TI - Mutations causing aspartylglucosaminuria (AGU): a lysosomal accumulation disease. AB - This article provides a review of the mutations reported so far in the lysosomal storage disease aspartylglucosaminuria (AGU). The clinical symptoms, biochemical findings, and diagnostic possibilities of the disease are introduced. The prevalence and biological consequences of the found mutations are then described, as well as the availability of a new rapid DNA test suitable for carrier screening. This test will be especially applicable in the genetically isolated Finnish population, where the carrier frequency of AGU was found to be as high as 1:36. Finally, future prospects dealing with the foreseeable therapeutic interventions of the disease are discussed. PMID- 1301946 TI - Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains. AB - The Marfan syndrome is an autosomal dominant heritable disorder of connective tissue with prominent involvement of the ocular, skeletal, and cardiovascular systems. The gene on chromosome 15 encoding fibrillin (FBN1), a 350-kDa glycoprotein component of the extracellular microfibril, is the site of defect in most, if not all cases. Complementary DNA sequence reveals a gene composed largely of epidermal growth factor-like repeats, each containing six predictably spaced cysteine residues. To date, two FBN1 gene missense mutations have been reported. Here we describe the identification of three new missense mutations in the FBN1 gene in patients with the Marfan syndrome. All of the 5 characterized missense mutations occur within the epidermal growth factor-like repeats of the FBN1 gene. In addition, 4 of 5 involve the substitution of cysteine residues and 3 of 5 substitute the third cysteine in the epidermal growth factor-like motif consensus sequence. These data suggest that defined residues within EGF-like domains of FBN1 have particular significance and, when altered, play a pivotal role in expression of the Marfan phenotype. PMID- 1301947 TI - A de novo phenylketonuria mutation: ATG (Met) to ATA (Ile) in the start codon of the phenylalanine hydroxylase gene. AB - We here describe the detection of a de novo mutation in the phenylalanine hydroxylase gene in a Norwegian phenylketonuria (PKU) patient. This novel mutation, M1I, disrupts the start codon of the gene by a G to A transition. The compound heterozygote genotype (IVS-12/M1I) of this patient predicts that no phenylalanine hydroxylase enzyme is formed, thus leading to a severe classical PKU. Determination of haplotypes and DNA fingerprint patterns indicates a paternal origin of the de novo mutation. PMID- 1301948 TI - CRIM-positive mutations of acute intermittent porphyria in Finland. AB - Acute intermittent porphyria (AIP) is a dominantly inherited metabolic disease caused by a partial deficiency of the third enzyme, porphobilinogen deaminase (PBGD), in the heme biosynthetic pathway. AIP has been divided into two subtypes according to the ratio of enzyme polypeptide concentration and enzyme activity measured in erythrocytes: cross-reacting immunologic material (CRIM) positive or negative. In this study six out of the seven known CRIM-positive AIP families in Finland were analyzed and two also previously identified mutations in the PBGD gene were found to be responsible for AIP in this genetically isolated population. The search for mutations was focused on exon 10 based on previously found mutations. SSCP analysis revealed a known polymorphism but the two mutations in that region were found only by direct sequencing of the PCR products. A G518-->A substitution changing Arg173 to Gln was found in three families and a C499-->T substitution changing Arg167 to Trp was detected in three families. DNA analyses of the family members revealed that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers for the AIP mutation. PMID- 1301949 TI - An N-acetylgalactosamine-4-sulfatase mutation (delta G238) results in a severe Maroteaux-Lamy phenotype. AB - Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomally inherited lysosomal storage disorder caused by a deficiency of N acetylgalactosamine-4-sulfatase (EC 3.1.6.1; 4-sulfatase). In order to determine the gene defect in a clinically severe MPS VI patient, polymerase chain reaction (PCR) products were generated from the patient's fibroblast mRNA and also from a 4-sulfatase cDNA clone and subjected to the chemical cleavage technique to detect mismatched bases, which were then identified by direct DNA sequencing of the PCR products. The patient was homozygous for an early frameshift mutation caused by the deletion of a G at position 238 (delta G238), which produces a truncated 4 sulfatase with an altered amino acid sequence from amino acid 80 to a premature stop codon at codon 113 relative to the normal 4-sulfatase reading frame of 533 amino acids. Since the mutation occurs only 40 amino acids past the signal peptidase cleavage site, it is most likely that this will result in a protein with no 4-sulfatase activity. This is consistent with the severe clinical presentation and the absence of 4-sulfatase enzyme activity or mutant 4-sulfatase protein in the patient. The patient was also found to be homozygous for two polymorphisms, i.e., a G to A transition at nucleotide 1072 resulting in a valine358 to methionine substitution (V358M) and a salient A to G transition in the third base of the proline397 codon at nucleotide 1191. PMID- 1301950 TI - Detection of sequence variants in the gene for human type II procollagen (COL2A1) by direct sequencing of polymerase chain reaction-amplified genomic DNA. AB - The direct sequencing of the human type II procollagen (COL2A1) gene from polymerase chain reaction (PCR)-amplified genomic DNA is described. Thirty-two regions of the COL2A1 gene were asymmetrically amplified with intron primers which were specifically chosen to amplify a region spanning 500 to 800 bp of sequence encoding one or more exons and their accompanying intervening sequences. Primers for dideoxynucleotide sequencing of the PCR products were then designed to provide complete exon sequence information and to insure that intron:exon splice junction sequence data would be obtained. Amplification and sequencing reactions were performed on an automated workstation to facilitate the handling of multiple DNA templates. The procedure allowed efficient sequencing of over 25,000 bp of each allele of the COL2A1 gene per diploid genome. We used this method for the comparative analyses of COL2A1 sequences in DNA isolated from the blood of 42 unrelated individuals and we identified 21 neutral sequence variants in the gene. The sequence variations were confirmed by independent assays, including restriction enzyme digestion. The sequence variants described here will be important for identifying haplotypes of the type II procollagen gene that will be useful in defining a genetic etiology for diseases of cartilaginous tissues. PMID- 1301951 TI - A modified approach to identification of the sickle cell anemia mutation by means of allele-specific polymerase chain reaction. AB - The allele-specific PCR approach has been modified by introducing a second mismatch at the 3'-penultimate link of the primer and used to identify the sickle cell anemia mutation (A-->T transversion in the sixth codon of the human beta globin gene causing Glu-->Val substitution in the protein), thus obviating the problem of an interpretationally ambiguous 3'-terminal mismatch including T residue. PMID- 1301952 TI - A novel beta-thalassemia mutation (G-->A) at the initiation codon of the beta globin gene. PMID- 1301953 TI - Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C in type 1 variants. PMID- 1301954 TI - Protein C deficiency: identification of a novel two-base pair insertion and two point mutations in exon 7 of the protein C gene in Spanish families. AB - We have applied single-strand conformation polymorphism (SSCP) to the analysis of exon 7 of the anticoagulant protein C (PC) gene, in 13 PC-deficient Spanish families. Abnormal patterns were visualized in three samples from type I or quantitative PC deficient proposita. A previously undescribed mutation due to a TT insertion after nucleotide 6139, between codons Gly-142 and Arg-143 was found in one family. The mutation (6139,ins TT) should result in a frameshift with a stop at codon 156, which agrees with the presence of a type I or quantitative PC deficiency in the affected members of the family. The second mutation identified was a C to T transition at nucleotide 6274, 9 base pairs into intron G. This mutation (6274,C-->T), found for the first time in a Spanish family, is identical to the previously characterized PC Sant Louis. The third mutation was a G to A transition that replaces arginine 178 with glutamine (178,R-->Q). This is the third case of 178,R-->Q mutation in 17 apparently unrelated Spanish families with type I PC deficiency. Furthermore, SSCP analysis allowed the detection of another previously described mutation in a PC-deficient Spanish family (178,R-->W). PMID- 1301955 TI - Gene duplication in evolution. PMID- 1301956 TI - Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. AB - The low density lipoprotein (LDL) receptor is a cell surface transmembrane protein that mediates the uptake and lysosomal degradation of plasma LDL, thereby providing cholesterol to cells. Mutations disrupting the function of this receptor produce autosomal dominant familial hypercholesterolemia (FH). Affected individuals have elevated plasma levels of LDL, which causes premature coronary atherosclerosis. To date, 71 mutations in the LDL receptor gene have been characterized at a molecular level. In this report, we describe 79 additional mutations and review the insights that all 150 mutations have provided into the structure/function relationship of the receptor protein and the clinical manifestations of FH. PMID- 1301957 TI - Molecular analysis of neurofibromatosis type 1 mutations. AB - We have examined a panel of 115 unrelated NF1 individuals for mutation in the 3' region of the NF1 gene, using Southern blotting and polymerase chain reaction amplification of exons followed by single-strand conformation polymorphism (SSCP) analysis. We found only 2 unequivocal mutations: a 571 bp deletion which removed exon 6 and resulted in a frameshift in exon 7, and a 2 bp deletion in exon 1. A third sequence variation detected by SSCP was predicted to cause a lysine arginine substitution in exon 6. This is a conservative change, and since the affected individual is a new mutation whose parents are not available, we cannot be sure of its biological significance. We detected mutations in at most 3% of individuals, from an analysis which covered 17% of the coding sequence by SSCP and a larger region by Southern blotting. This relative failure to detect mutations accords with the experience of others. Even allowing for the incomplete sensitivity of the methods used, the results suggest that the majority of NF1 mutations lie elsewhere in the coding sequence or outside it. PMID- 1301958 TI - An unusual genotype in an Ashkenazi Jewish patient with Tay-Sachs disease. AB - The Ashkenazi Jewish population is enriched for carriers of a fatal form of Tay Sachs disease, a recessive inherited disorder caused by mutations in the alpha chain of the lysosomal enzyme beta-hexosaminidase A. Approximately 20% of the Ashkenazi carriers harbor a splice junction defect while about 78% bear a 4 base pair (bp) insertion. However, the Ashkenazi Jewish patient used in the original description of the 4 bp insertion carried this lesion in only 1 allele and was negative for the splice junction mutation. We cloned the insertion negative allele and by sequence analysis of the exons found a point mutation in exon 11 that results in substitution of Trp392 with a premature termination codon. Nine Ashkenazi Jewish carriers that tested negative for the major and minor mutations as well as for a lesion causing an adult form of Tay-Sachs disease did not carry the base change defect, suggesting that it may be a recent and/or rare mutation. This finding also indicates that screening the Ashkenazi population solely by recombinant DNA methods for the splice junction, 4 bp insertion, and adult mutations may result in occasional false negatives. PMID- 1301959 TI - Two novel mutations responsible for hereditary type I protein C deficiency: characterization by denaturing gradient gel electrophoresis. AB - Hereditary protein C (PC) deficiency is usually associated with a high risk of thrombosis. We report the results of a study undertaken to screen for molecular defects in families with hereditary quantitative PC deficiency. Using a strategy combining polymerase chain reaction amplification of selected gene fragments, denaturing gradient gel electrophoresis of the amplification products, and direct sequencing of fragments with altered melting behavior, we studied the PC gene exons and exon/intron junctions of subjects with hereditary type I PC deficiency. Computer simulation of DNA melting was used to design several sets of primers, each containing a GC-clamp, permitting the complete analysis of each amplified exon sequence. Using this procedure, we identified two previously undescribed mutations located in exon VII: a C-to-T substitution generating a nonsense codon in place of Arg 157 in the mature PC and a G-to-A substitution converting Arg 178 to GIn. The two mutations were detected in, respectively, 3 and 2 apparently independent families. This strategy is therefore a valuable tool for screening patients, and the results emphasize its advantages over plasma assays in individuals with a family history of thrombosis. PMID- 1301960 TI - Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis. PMID- 1301961 TI - Impaired urinary excretion of soluble IL-2 receptors in patients with systemic lupus erythematosus and rheumatoid arthritis. AB - Several previous studies have demonstrated increased in vivo release of soluble interleukin-2 receptors (sIL-2R) in patients with disorders associated with cellular activation. In this study attempting to understand better the role of sIL-2R released in vivo, we investigated the sIL-2R levels in paired serum and urine samples from 25 patients with systemic lupus erythematosus (SLE), 41 patients with rheumatoid arthritis (RA) and 20 healthy subjects. Using an ELISA for sIL-2R, we detected significantly increased urinary sIL-2R levels in normal individuals (868 +/- 114 units/ml) compared to the corresponding serum samples (209 +/- 25, P < 0.001, mean urine/serum sIL-2R ratio: 4.5 +/- 0.6), which suggests that the clearance of sIL-2R from circulation is largely kidney dependent. The patients with SLE and RA exhibited significantly increased serum sIL-2R levels compared to normals (682 +/- 115 and 734 +/- 101 units/ml, respectively, P < 0.001) and these levels correlated with disease activity. However, urinary excretion of sIL-2R in these patients (SLE: 620 +/- 154 units/ml; RA: 1084 +/- 148 units/ml) was found to be significantly decreased (mean urine/serum sIL-2R ratio in SLE: 0.9 +/- 0.2; in RA: 1.9 +/- 0.2; P < 0.001) compared to normals, possibly contributing to the accumulation of these soluble receptors in the serum of autoimmune patients after their release from cells. Our findings can be attributed either to the binding of the sIL-2R to serum protein(s) or to distinct structural features of serum sIL-2R in SLE and RA patients, interfering with the urinary excretion of these molecules. PMID- 1301962 TI - Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T cell activation markers. AB - We examined cerebrospinal fluid (CSF) samples from 12 patients with SLE and active central nervous system (CNS) involvement for their levels of the following cytokines: interleukin-1 (IL-1) by means of two different assays--the IL-1 responsive murine cell line LBRM 33-la5 and an ELISA for IL-1 alpha; IL-2 by means of the CTLL cell line responsive to it; and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) both determined by a specific ELISA. We found that SLE CSF had significantly higher levels of IL-1 and IL-6 than did those obtained at surgery from eight controls without inflammatory neurologic disease. IL-2 and TNF were not detectable in any of the CSF samples. We also studied the status of activation in CSF T cells using monoclonal antibodies against early (anti-IL-2R (CD25) and anti-transferrin (CD71)), late (anti-T10) and very late (anti-VLA-1) activation antigens, and found increased percentages of T10-bearing (18 +/- 2 vs 3 +/- 0.7%) and VLA-1-bearing T cells (12 +/- 2 vs 0.7 +/- 0.2%) in SLE patients as compared to controls (both P < 0.01). Levels of IL-1 and IL-6 correlated with T10 and those of IL-1 correlated also with VLA-1. Markers of early T-cell activation did not differ in SLE and control CSF. Because of these findings we analysed the effect of recombinant IL-1, IL-6 or normal CSF on normal T cells and found that they did not induce the expression of activation markers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301964 TI - Cofactors involved in the antiphospholipid syndrome. PMID- 1301963 TI - Small nuclear ribonucleoprotein particles contain glycoproteins recognized by rheumatic disease-associated autoantibodies. AB - Proteins from U1 and U2 small nuclear ribonucleoprotein (snRNP) particles, which are common targets of autoantibodies found in some rheumatic diseases, were analysed for the presence of glycans. A glycan detection assay revealed that the U1-specific proteins 68K and A and the U2-specific protein B" are glycosylated. However, none of the Sm proteins, which are common to all the major snRNP particles, showed a detectable level of glycosylation. With the use of specific lectins, an analysis of the particular carbohydrate(s) attached to the U1 snRNP 68K protein demonstrated the presence of at least one N-linked oligosaccharide chain. Lectin detection of galactose, glucose, mannose and N-acetylglucosamine on 68K was confirmed by chemical analysis of the carbohydrates. The glycopeptide nature of these antigens may be important for understanding the role of autoantigens in the pathogenesis of autoimmune disorder. PMID- 1301965 TI - The clinical genetics of lupus. AB - Genetic aspects of lupus are reviewed, including recognition of genetic and clinical heterogeneity, genetic factors in the aetiology and heritability of disease, reproductive implications and genetic counselling of patients. Despite a large literature on the genetic epidemiology and immunogenetics of lupus, it remains difficult to apply the results of laboratory findings to the circumstances of individual patients. Generally, lupus is not transmitted as a simple Mendelian trait, and genetic counselling is based on the multifactorial model of disease aetiology with interaction of multiple genetic and environmental factors. Further studies are needed to clarify the heritability of lupus and improve the data for recurrence risk prediction in lupus families. PMID- 1301966 TI - Autoimmunity, polyclonal B-cell activation and infection. AB - It is widely believed that autoimmunity is an integral part of the immune system, and that genetic, immunologic, hormonal, environmental and other factors contribute to the pathogenesis of autoimmune disease. Thus, autoimmune disease may represent an abnormal expression of immune functions instead of loss of tolerance to self, and it can be organ specific or systemic in its manifestations. We review the various factors that contribute to the development of autoimmune disease; we also review the mechanisms of polyclonal B-cell activation, with emphasis on the role of infectious agents. We consider systemic lupus erythematosus in humans and in experimental animals as prototypic autoimmune disease, and we summarize data to indicate that polyclonal B-cell activation is central to the pathogenesis of systemic autoimmune disease. The effect of polyclonal B-cell activation, brought about by injections of a B-cell activator-lipopolysaccharide from Gram-negative bacteria-is sufficient to cause autoimmune disease in an immunologically normal host. In fact, autoimmune disease can be arrested if excessive polyclonal B-cell activation is suppressed; alternatively, autoimmune disease can be exacerbated if polyclonal B-cell activation is enhanced. We explore the mechanism of tissue injury when autoimmune disease is induced or exacerbated, and we consider the pathogenic roles of autoantibodies, immune complexes, complement, the blood cell carrier system, and the mononuclear phagocyte system. Although polyclonal B-cell activation may be the mechanism whereby various factors can cause or exacerbate systemic autoimmune disease, polyclonal B-cell activation may cause autoimmune disease on its own. PMID- 1301967 TI - A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. AB - Anticardiolipin antibodies (aCL) purified from patients with autoimmune disease have recently been shown to interact with a phospholipid-binding plasma protein, beta 2-glycoprotein I (beta 2-GPI). The aim of this study was to determine whether aCL purified from patients with infection also interact with beta 2-GPI. aCL purified from 23 patients with malaria, infectious mononucleosis, tuberculosis, hepatitis A or syphilis did not require the presence of beta 2-GPI to bind cardiolipin (CL). In contrast, aCL were purified from 11 out of 12 patients with autoimmune disease that bound CL only in the presence of beta 2 GPI. Thrombotic complications appear to be associated with aCL occurring in autoimmune disease but not with aCL associated with infections. We postulate that this increased risk of thrombosis in the autoimmune group may be due to the presence of aCL that bind CL in association with beta 2-GPI, a plasma protein with anticoagulant activity. PMID- 1301968 TI - Antiphospholipid antibodies differ in aPL cofactor requirement. AB - Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta 2-glycoprotein I (beta 2GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified beta 2GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to beta 2GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if beta 2GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications. PMID- 1301969 TI - Distribution of two common idiotypes of anticardiolipin antibodies in sera of patients with primary antiphospholipid syndrome, systemic lupus erythematosus and monoclonal gammopathies. AB - The frequency of two common idiotypes of anticardiolipin antibodies (aCL) was determined in sera from three groups of subjects, patients with systemic lupus erythematosus (SLE), with primary antiphospholipid syndrome (PAPS) and with monoclonal gammopathies (MG), as compared to normal population. The idiotype 1.10, which was derived from a patient with active SLE and antiphospholipid syndrome, was found more frequently among patients with PAPS (10.5%, 10.5% and 22.2% in MG, SLE and PAPS, respectively) than the idiotype H3, which was derived from a human hybridoma monoclonal aCL generated from a healthy subject immunized with tetanus and diphtheria. The latter idiotype was detected in 8.7%, 6.5% and 11.7% of patients with MG, SLE and PAPS, respectively. Incidental findings in this study include a high prevalence of aCL among patients with MG (23%) and a high prevalence of anti-dsDNA antibodies, detected only by a sensitive enzyme linked immunosorbent assay, among patients with PAPS. Our results indicate that idiotypic diversity exists among aCL derived from different sources. Some of these cross-reactive idiotypes may be more pathogenic than others. PMID- 1301970 TI - The long-term clinical outcome of 56 patients with biopsy-proven lupus nephritis followed at a single center. AB - We retrospectively evaluated the clinical outcome of 45 female and 11 male patients with biopsy-proven lupus nephritis, followed at our hospital between February 1974 and February 1990. In the majority signs of nephritis were present at the time systemic lupus erythematosus was diagnosed (range: -42-156 months) and the median time from onset of nephritis to biopsy was 2 months. The median follow-up from the time of the biopsy was 53.5 months (range: 2-192), the median age at biopsy 25 years and the median serum creatinine level 1.2 mg/dl. Initial renal biopsies had the following histopathological classes according to the World Health Organization criteria (n): I (2); II (10); III (10); IV (28); V (5); VI (1). Over the study period active episodes were treated with high-dose oral prednisone alone or combined with intravenous nitrogen mustard and oral chlorambucil (1974-75), azathioprine (1978-86), cyclophosphamide (1986-90) and/or plasma-exchange (1976-84). These strategies were based on literature data or multicenter studies in which we participated. Eight patients developed end-stage renal disease (ESRD) (median: 47 months post-biopsy; range: 20-120). In these, initial biopsies showed class IV in seven, and class V in one. Confounded risk factors for ESRD were class IV biopsy, male gender and serum creatinine level above 1.4 mg/dl. The calculated proportion without ESRD 5 years post-biopsy was 87% (95% confidence limits: 98-76%), and at 10 years 70% (95% confidence limits: 90-49%). Five patients (11.2%) died; causes of death were cerebrovascular accident (n = 2), cerebral lupus (n = 2) and S. aureus sepsis (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301971 TI - Sex steroids and SLE: metabolism of androgens to estrogens. PMID- 1301972 TI - Lupus pernio. AB - Thirty-five patients with lupus pernio have been observed in a series of 818 patients with clinical and histological evidence of sarcoidosis. This analysis provides the natural history of lupus pernio and its associated clinical and radiological features. It predominates in women, and particularly in West Indians. The chronic persistent violaceous skin lesions have a predilection for the nose, cheeks, lips, eyelids, ears and fingers, ranging from a few nodules under the tip of the nose to exuberant plaques spreading across the nose and both cheeks. There was intrathoracic involvement in 74% of patients, upper respiratory tract disease in 54%, reticulo-endothelial involvement in 54%, bone cysts in 43% and ocular lesions in 37%. It is distinguished from lupus vulgaris and lupus erythematosus by clinical features, histology and radiology. PMID- 1301973 TI - Canine systemic lupus erythematosus. I: A study of 75 cases. AB - We studied 75 cases of canine systemic lupus erythematosus (SLE) presenting with at least four criteria of the American Rheumatism Association (ARA), including antinuclear antibodies (ANAb). This disease mainly affects male German shepherds of an average age of 5 years. The most common clinical signs are polyarthritis (91% of cases), and renal (65%) and cutaneo-mucous disorders (60%). Hemolytic anemia is rare (13%). ANAb are present, often at high levels (> 256 up to 10(6) by indirect immunofluorescence on mouse blood smears). The titers are correlated with the severity and the stage of the disease. As double-stranded DNA Ab are rare and as antihistone Ab are frequent, the former could be replaced by the latter in the ARA criteria applied to the SLE dog. Another category of ANAb, named anti-type 1, also seems useful in diagnosing canine SLE. As for therapy, long-term remissions (up to 9 years without treatment) were obtained in 55.6% of 27 SLE dogs treated by levamisole. At first, levamisole was associated with induction corticotherapy, then administered alone and finally discontinued. Side effects were uncommon and transient. PMID- 1301974 TI - Prevalence of non-organ-specific autoantibodies in pregnant and non-pregnant healthy women. AB - The prevalence of autoantibodies during pregnancy was studied. Sera from 568 women (203 pregnant and 365 non-pregnant) were tested for autoantibodies to double-stranded DNA, cardiolipin and extractable cellular antigens. Nineteen out of 203 pregnant women (9.4%) had at least one autoantibody against double stranded DNA or cardiolipin, mainly of the IgM class. The non-pregnant control group had significantly higher incidence of autoantibodies (17.8%; chi 2 = 7.39, P < 0.01). Sixty-six out of 568 women had had spontaneous abortions in their past medical history, but there was no correlation between them and the presence of anticardiolipin antibodies. Two of the non-pregnant women had anti-Ro(SSA) antibodies. These findings suggest that (a) the prevalence of autoantibodies decreases during pregnancy; and (b) the presence of anticardiolipin antibodies in healthy pregnant women does not correlate with any pregnancy-related complications. However, our results indicated that autoimmunity is a rather common disorder in healthy women. PMID- 1301975 TI - Serum apolipoprotein H levels in systemic lupus erythematosus are not influenced by antiphospholipid antibodies. AB - Anticardiolipin antibodies (aCL) were recently discovered to recognize a complex consisting of phospholipids and apolipoprotein H (apo H). In this study, we determined the serum apo H levels in 36 systemic lupus erythematosus (SLE) patients with or without antiphospholipid antibodies (aPL), including aCL and lupus anticoagulants, to clarify the possible effects of aPL on apo H levels in vivo. The apo H levels were low in SLE patients as compared with 22 healthy controls. However, no associations were found between apo H levels and circulating aPL or clinical features of the antiphospholipid antibody syndrome. A secondary hyperlipidemic state, which probably related to lupus nephritis (proteinuria) and/or prednisolone treatment, increased apo H levels in SLE patients. PMID- 1301976 TI - Antigen-binding diversity of human hybridoma autoantibodies derived from splenocytes of patients with SLE. AB - The antigen-binding specificity of human hybridoma-derived monoclonal autoantibodies (mAb) was analysed with mAbs derived from the spleens of two patients with active systemic lupus erythematosus (SLE). From one patient 72 mAbs (RSP clones) and from the other 173 mAbs (RT clones) were obtained. The binding specificity of these mAbs was analysed by solid- and fluid-phase ELISA against the autoantigens ssDNA, dsDNA, cardiolipin, SmRNP, histones, Sm-D and SS-B (La) synthetic peptides, and foreign antigens including bacterial polysaccharides. In addition, antinuclear antibody activity and anti-dsDNA binding were confirmed by fluorescence staining methods. Reflecting the patient's serological profile, none of the antibodies from the RSP clones reacted with ssDNA or dsDNA but 12 reacted with cardiolipin. In addition, three mAbs reacted with H4, five with U1 RNP, two with Sm-D peptides and 12 with SS-B peptides. In contrast, from the RT fusion, nine mAbs reacted with ssDNA, HI and SS-B peptides, seven with cardiolipin, four with dsDNA, two with Sm-D peptides and one each with H2A, H3 and H4. In many cases one mAb showed reactivity with more than one antigen: for example, mAb RT 72 binds to ssDNA, dsDNA, cardiolipin, H1, H4 and an Sm-D peptide; RT 6 binds to H1, SmRNP and ubiquitinated histone H2A. However, none of the antibodies showed 'across the board' polyreactivity; indeed, the selectivity of the reactions was notable and marked variation in antibody affinity was recorded. Eight of the mAbs bound to Salmonella typhimurium and two to the Klebsiella polysaccharide K 30.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1301977 TI - DNA binding to mouse cells is mediated by cell-surface molecules: the role of these DNA-binding molecules as target antigens in murine lupus. AB - Autoimmunity to a 28-29-kDa cell-surface DNA-binding molecule has previously been described in patients with systemic lupus erythematosus and related autoimmune diseases. This report describes experiments that implicate a similar antigen antibody system in the evolution of autoimmunity in lupus-prone mice. DNA binding to murine spleen cells was found to be a saturable phenomenon that was inhibited by excess cold DNA and trypsinization. The role of autoimmunity to murine cell surface DNA-binding molecules in lupus-prone mice (MRL lpr/lpr, MRL +/+, BXSB) was compared to normal mice (BALB/c, C3H.SW) by means of an assay that measured the inhibition of cell-surface DNA binding. Only sera from lupus strains had inhibitory activity and this component was shown to be an IgM autoantibody. Furthermore, we isolated a spontaneously occurring IgM monoclonal antibody from the spleen of an MRL/lpr mouse, which inhibited DNA binding to mouse cells. Time course studies indicated that young female MRL/lpr mice lacked detectable activity against cell-surface DNA-binding molecules; however, by 8-10 weeks maximal inhibitory activity was observed. This response occurred prior to the development of significant antinuclear antibody activity. With the appearance of overt disease and anti-DNA antibodies, inhibition of DNA-binding activity became undetectable. These findings mirror previous studies on autoimmunity to a cell surface DNA-binding molecule on human leucocytes, but have the added advantage of permitting the study of the temporal evolution of this inhibitory activity in relation to disease expression. PMID- 1301978 TI - Antiganglioside antibodies in patients with neuropsychiatric systemic lupus erythematosus. AB - Antiganglioside antibodies (AGA) were determined in sera and cerebrospinal fluids (CSF) from 50 systemic lupus erythematosus (SLE) patients, and age-matched normal controls. The SLE patients were subdivided according to the type of clinical manifestation into two groups: neuropsychiatric SLE and active SLE without neuropsychiatric manifestation. The presence of these antibodies showed a significant correlation between IgG AGA in the CSF and IgM AGA in the serum and neuropsychiatric SLE. Fifteen patients had this antibody in the CSF without detectable levels in the serum. No correlation was seen between anticardiolipin antibodies in the serum of CSF and neuropsychiatric SLE. The present work suggests that antibodies against gangliosides may be a marker for neuropsychiatric SLE and that intrathecal antibody production can result in the development of this manifestation. PMID- 1301979 TI - The sequelae of chronic cutaneous lupus erythematosus. AB - Eighty-six patients with chronic cutaneous lupus erythematosus were examined. Twelve of these also suffered from systemic lupus erythematosus. The mean duration of the disease was 15.1 years. Fifty-seven percent of patients (49/86) had scarring of some kind producing destruction and deformity; 47% (41/86) had scarring of glabrous surfaces and 35% (30/86) had scarring alopecia; 35% (30/86) were also suffering from pigmentary disturbance. The details and treatment of these and other non-scarring sequelae are discussed. PMID- 1301980 TI - Management of antiphospholipid antibody positivity and elective orthopedic procedures. AB - Current management of primary or secondary antiphospholipid antibody (aPL) syndromes with known embolic phenomena requiring anticoagulation is empiric in the setting of elective orthopedic procedures. Short-term withdrawal of warfarin with continuance of aspirin and glucocorticoid therapy was undertaken for sequential bilateral knee replacements in a lupus patient with aPL. Her course was successfully managed without thrombo-embolic complications. PMID- 1301981 TI - Plasma sex hormones and aromatase activity in tissues of patients with systemic lupus erythematosus. AB - Clinical observations and experimental data suggest that sex hormones influence the development of systemic lupus erythematosus (SLE). An imbalance between androgen and estrogen plasma levels may suggest an abnormality in the aromatase activity involved in estradiol synthesis. Aromatase activity in skin and subcutaneous tissue and plasma sex-hormone levels (testosterone, androstenedione, estrone, estradiol, dehydrosterone sulfate, cortisol) were measured in 15 SLE patients (nine female, six male) who had never received corticosteroid treatment and in eight (four female, four male) healthy control subjects. There was a tendency toward an increase in aromatase activity in SLE patients when compared to control subjects. Among SLE patients the aromatase activity varied inversely with disease activity. Patients with SLE had decreased androgen and increased estrogen levels. Aromatase activity in SLE patients had significant direct correlation with estrogen levels. These data suggest that abnormal regulation of aromatase activity may partially explain the abnormalities of estrogen synthesis in SLE. PMID- 1301982 TI - Prediction of outcome in lupus nephritis. PMID- 1301983 TI - Multiorgan thrombotic disorders in systemic lupus erythematosus: a common link? AB - Multiorgan thrombotic disorders have been described in a variety of conditions including systemic lupus erythematosus. Among these are the 'catastrophic' antiphospholipid syndrome, disseminated intravascular coagulation and the thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome. In this review we briefly analyse some specific clinical and haematological characteristics of these conditions and attempt to uncover common links between them. PMID- 1301984 TI - Can experienced clinicians predict the outcome of lupus nephritis? AB - The ability of four experienced clinicians to predict short-term outcome (serum creatinine level at 1 year) and long-term outcome (renal insufficiency) was evaluated in 87 patients with lupus nephritis. The correlational agreement and the accuracy of their predictions were contrasted with the actual outcomes observed and with statistically generated prognostic regression models. In contrast to previously published data, all four clinicians predicted both short term outcomes (P < 0.001) and long-term outcomes (P < 0.02) well. The clinicians' predictions approximated that of a statistically generated computer model for both agreement and accuracy for renal function at 1 year. The four clinicians identified nearly identical clinical variables as important in determining prognosis. Provision of biopsy data to the clinicians improved short-term and long-term prediction slightly. The value of the statistical models was 'validated' by demonstrating that three of the four clinical variables identified by the models, but not by the clinicians, could enhance clinical prediction (P < 0.05). In addition, the extent of tubulo-interstitial involvement on biopsy, a predictor that has recently received increased attention, could improve the long term clinical predictions of all four clinicians (P < 0.05). PMID- 1301985 TI - I-123 iofetamine SPECT scan in systemic lupus erythematosus patients with cognitive and other minor neuropsychiatric symptoms: a pilot study. AB - Accurate diagnosis of central nervous system (CNS) lupus remains difficult, especially when the manifestations are of subtle cognitive and affective changes. This pilot study reports on the use of I-123 iofetamine single photon emission computerized tomography (SPECT) scans in 18 such patients with documented systemic lupus erythematosus. Eight of the 18 scans were abnormal (44%), four in a diffuse bi-temporo-parietal pattern previously noted only in Alzheimer's disease, and four with large focal deficits. Neither the existence of the abnormal scan nor the particular pattern of abnormality correlated with the results of other diagnostic tests. These preliminary results raise the possibility that SPECT scans may offer an additional valuable diagnostic instrument in CNS lupus, although further studies are necessary to delineate their precise role. PMID- 1301986 TI - Prevalence of acne rosacea in a rheumatic skin disease subspecialty clinic. AB - There are many causes of malar erythema besides the classic butterfly rash of acute cutaneous lupus erythematosus (LE). Twenty-one patients (6.7% of new patient visits) referred to a dermatology department-based rheumatic skin disease subspecialty clinic over a 5-year period in whom a diagnosis of cutaneous LE had been entertained were found to have diagnoses other than autoimmune connective tissue diseases. Sixteen of the patients in this cohort (76%) had acne rosacea (rosacea), while the remaining five had other dermatologic disorders. Review of their records revealed that upon referral nine of these 21 patients (43%) had positive antinuclear antibody (ANA) assays, most with insignificant or marginal titers by our laboratory standards. On repeat ANA testing in our laboratory, all of these patients had insignificant ANA titers. Physicians may be giving too much weight to low-titer ANAs in assessing patients with isolated malar erythema. These issues are discussed in the overall context of the differential diagnosis of malar erythema. A simple punch skin biopsy can be very helpful in distinguishing cutaneous LE from other causes of malar erythema. PMID- 1301987 TI - Monoclonal autoantibodies to cardiolipin derived from SLE mice. AB - The objective of this study was to clarify the specificity of anticardiolipin antibodies (aCL). Eighteen monoclonal hybridoma aCL from systemic lupus erythematosus (SLE)-prone MRL/Mp-lpr/lpr mice were established, and the reactivity of monoclonal aCL to phospholipids, DNA, nuclei of human epithelial cells, platelets, vascular endothelial cells, heparin, protein C and thrombomodulin was examined. All the 18 monoclonal aCL reacted with phosphatidylserine and some showed reactivity to phosphatidylinositol and phosphatidylcholine. Six of 16 monoclonal aCL were demonstrated to have the property of lupus anticoagulant. Monoclonal aCL were classified into three categories, in terms of DNA-binding specificity. Ten of 18 aCL had characteristics of antinuclear antibodies. Six of 11 aCL reacted with platelets. Three of 18 aCL were bound to vascular endothelial cells and to heparin. No monoclonal aCL reacted with protein C or thrombomodulin. Therefore, the conclusion was made that monoclonal aCL from SLE mice showed a polyspecific nature. PMID- 1301988 TI - Two sisters producing anti-U1RNP exhibit serological concordance and clinical discordance. AB - Two sisters had autoimmune responses to the U1RNP particle that were quantitatively similar and/or identical in molecular characteristics. No other autoantibodies were demonstrable. Both sisters immunoprecipitated only U1RNA, had a reaction of identity in gel diffusion, bound the 68-kDa band in HeLa cell extract in Western blot, and reacted almost equally to a rabbit anti-idiotypic reagent made against either sister's isolated anti-U1RNP Fab fragments. They both carried a DR4 allele, which has been associated with anti-U1RNP production in several studies. While the sisters both had Raynaud's phenomenon, their clinical pictures were otherwise dissimilar. One had a seizure disorder (Ju); the other had polymyositis and features of scleroderma (Je). In sister Ju, Raynaud's phenomenon was manifest for the first time in association with the appearance of precipitating anti-U1RNP. PMID- 1301989 TI - Bacterial lipopolysaccharide causes variable deposits of diverse immunoglobulin isotypes in kidneys of lupus-prone mice. AB - We investigated the role of immunoglobulin isotypes in the exacerbation of lupus nephritis associated with exposure to bacterial lipopolysaccharide. The data indicate that enhanced polyclonal B-cell activation and exacerbated autoimmune disease evoked by lipopolysaccharide are associated with an increase in the concentration of isotypes in plasma and in renal eluate, that this isotype response is polyclonal and preferential but not restrictive, that all B cells are responsive but all are not equally sensitive to the effects of lipopolysaccharide, and that some expanded isotypes may be more nephritogenic in certain strains of lupus-prone mice. PMID- 1301990 TI - Monoclonal gammopathy in systemic lupus erythematosus. AB - In order to ascertain the incidence of monoclonal gammopathy (MG) in systemic lupus erythematosus (SLE), 120 SLE patients were evaluated. Four patients (3.3%), two of whom were under 50 years of age, were found to have a monoclonal immunoglobulin in their serum. Our data agree with the previous literature in demonstrating a higher incidence of MG in SLE patients in comparison with the general population. Neither the clinical importance nor the pathogenetic significance of this association is known. PMID- 1301991 TI - Prevalence of anticardiolipin antibodies in subacute cutaneous lupus erythematosus. AB - We examined the prevalence of the antibodies to cardiolipin measured by solid phase enzyme immunoassay during a prospective study of patients with subacute cutaneous lupus erythematosus (SCLE). Seven of 44 (16%) consecutive patients with SCLE had positive anticardiolipin antibodies; of these only three satisfied the American Rheumatism Association's revised criteria for the classification of systemic lupus erythematosus. Clinical findings probably associated with the positive anticardiolipin antibodies were found in four cases, including clotting abnormalities, thrombocytopenia, hemolytic anemia, livedo reticularis, chilblain lupus erythematosus lesions, migraine, leg venous thrombosis and pulmonary embolism after surgery, and spontaneous abortion. Our data suggest that it is reasonable to screen SCLE patients for these antibodies to confirm the presence of the antiphospholipid syndrome. PMID- 1301992 TI - Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. AB - Diabetes mellitus (DM) is one of the most common chronic disorders of children and adults. Several reports have suggested an increased incidence of maternal transmission in some forms of DM. Therefore, we tested a pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations and discovered a 10.4 kilobase (kb) mtDNA deletion. This deletion is unique because it is maternally inherited, removes the light strand origin (OL) of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of mtDNA deletion syndromes. This discovery demonstrates that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics. PMID- 1301993 TI - Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome. AB - The peroxisomal membrane protein, with a relative molecular mass of 70,000 (M(r) 70K) (PMP70), is an important component of peroxisomal membranes and an ATP binding cassette protein. To investigate its possible involvement in Zellweger syndrome (ZS), an inborn error of peroxisome assembly, we cloned and sequenced cDNAs for human PMP70 and mapped the gene to chromosome 1. Amongst 32 probands with ZS or related disorders, we found two mutant PMP70 alleles in single ZS probands from the same complementation group. One allele has a donor splice site mutation and the second a missense mutation. Our results suggest that PMP70 plays an important role in peroxisome biogenesis and that mutations in PMP70 may be responsible for a subset of ZS patients. PMID- 1301994 TI - Rapid generation of region specific probes by chromosome microdissection and their application. AB - The strategy presented here to identify unequivocally cryptic chromosomal rearrangements has relevance to both prenatal and postnatal cytogenetic analysis as well as the analysis of tumour-associated chromosome rearrangements. Microdissection and in vitro amplification of specific chromosomal regions are performed, followed by labelling for fluorescent in situ hybridization (FISH) to normal metaphase chromosomes (Micro-FISH). Micro-FISH probes have been used successfully to determine the derivation of chromosome segments unidentifiable by standard chromosome banding analysis. Micro-FISH probes (created in less than 24 hours) now make it possible to identify explicitly the chromosome constitution of virtually all cytologically visible chromosome rearrangements. PMID- 1301995 TI - Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. AB - Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy in humans, characterized electrophysiologically by decreased nerve conduction velocities (NCVs). CMT1A is associated with a large submicroscopic DNA duplication in proximal 17p. In this report we demonstrate that a patient with a cytogenetically visible duplication, dup(17)(p11.2p12), has decreased NCV. Molecular analysis demonstrated this patient was duplicated for all the DNA markers duplicated in CMT1A as well as markers both proximal and distal to the CMT1A duplication. These data support the hypothesis that the CMT1A phenotype can result from a gene dosage effect. PMID- 1301996 TI - Positional cloning: let's not call it reverse anymore. PMID- 1301998 TI - Definition of a consensus binding site for p53. AB - Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo. PMID- 1301997 TI - Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3. AB - A total of 116,118 basepairs (bp) derived from three cosmids spanning the ERCC1 locus of human chromosome 19q13.3 have been sequenced with automated fluorescence based sequencers and analysed by polymerase chain reaction amplification and computer methods. The assembled sequence forms two contigs totalling 105,831 bp, which contain a human fosB proto-oncogene, a gene encoding a protein phosphatase, two genes of unknown function and the previously-characterized ERCC1 DNA repair gene. This light band region has a high average density of 1.4 Alu repeats per kilobase. Human chromosome light bands could therefore contain up to 75,000 genes and 1.5 million Alu repeats. PMID- 1301999 TI - Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut. AB - Human CCAAT displacement protein (CDP), a putative repressor of developmentally regulated gene expression, was purified from HeLa cells by DNA binding-site affinity chromatography. cDNA encoding CDP was obtained by immunoscreening a lambda gt11 library with antibody raised against purified protein. The deduced primary amino acid sequence of CDP reveals remarkable homology to Drosophila cut with respect to the presence of a unique homeodomain and "cut repeats". As cut participates in determination of cell fate in several tissues in Drosophila, the similarity predicts a broad role for CDP in mammalian development. PMID- 1302000 TI - Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. AB - Cretinism is marked by irreversible mental and growth retardation. We describe here an entirely new case of cretinism showing combined pituitary hormone deficiencies of thyrotropin, growth hormone and prolactin that appears to be caused by homozygosity for a nonsense mutation in the gene for the pituitary specific transcription activator, Pit-1/GHF-1 (designated PIT1 in humans for pituitary specific factor 1). This is the first report in humans of a defect in a transcription activator causing deficiency of multiple target genes. PMID- 1302002 TI - Heritable unstable DNA sequences. PMID- 1302001 TI - A mutation in adenylosuccinate lyase associated with mental retardation and autistic features. AB - We have examined the molecular basis of three cases of severe mental retardation with autistic features in one family. A point mutation in a purine nucleotide biosynthetic enzyme, adenylosuccinate lyase (ASL), segregates with the disorder. The affected children are homozygous for the point mutation while the parents and all four unaffected children are heterozygous. The point mutation is absent in control subjects. The point mutation results in a Ser413Pro substitution which leads to structural instability of the recombinant mutant enzyme, and this instability lowers ASL levels in lymphocytes. These observations suggest that the instability of ASL underlies the severe developmental disorder in the affected children, and that mutations in the ASL gene may result in other cases of mental retardation and autistic features. PMID- 1302003 TI - Aberrant splicing of the CHM gene is a significant cause of choroideremia. AB - Choroideremia (CHM) is an X-linked progressive degeneration of the choroid and retina. 12% of unrelated male patients carry deletions of the partially cloned CHM gene. In Finland, there are more than 120 living CHM patients belonging to eight apparently unrelated pedigrees. Molecular deletions involving the CHM gene have been detected in three families. We have screened the remaining five families for point mutations. In one large family a single nucleotide (T) insertion into the donor splice site of exon C leads to two aberrantly spliced mRNAs both producing a premature stop codon. The mutation can be assayed easily by amplification and digestion with Msel. Our findings provide additional evidence for the pathogenetic role of CHM mutations and provide a diagnostic tool for one fifth of the world's known CHM patients. PMID- 1302004 TI - A survey of expressed genes in Caenorhabditis elegans. AB - As an adjunct to the genomic sequencing of Caenorhabditis elegans, we have investigated a representative cDNA library of 1,517 clones. A single sequence read has been obtained from the 5' end of each clone, allowing its characterization with respect to the public databases, and the clones are being localized on the genome map. The result is the identification of about 1,200 of the estimated 15,000 genes of C. elegans. More than 30% of the inferred protein sequences have significant similarity to existing sequences in the databases, providing a route towards in vivo analysis of known genes in the nematode. These clones also provide material for assessing the accuracy of predicted exons and splicing patterns and will lead to a more accurate estimate of the total number of genes in the organism than has hitherto been available. PMID- 1302006 TI - Construction of a mouse yeast artificial chromosome library in a recombination deficient strain of yeast. AB - We have constructed a new generation yeast artificial chromosome (YAC) library from female C57BL/10 mice in a recombination-deficient strain of Saccharomyces cerevisiae carrying a mutation in the RAD52 gene. The YAC library contains 41,568 clones with an average insert size of 240 kilobases, representing a greater than threefold coverage of the mouse genome. Currently, the library can be screened by polymerase chain reaction and we have isolated positive clones at a number of loci in the mouse genome. This rad52 library should enable a long-term assessment of the effect of one of the yeast recombination pathway genes on both, genome wide YAC clone stability and the frequency of chimaeric clones. PMID- 1302005 TI - Caenorhabditis elegans expressed sequence tags identify gene families and potential disease gene homologues. AB - A database containing mapped partial cDNA sequences from Caenorhabditis elegans will provide a ready starting point for identifying nematode homologues of important human genes and determining their functions in C. elegans. A total of 720 expressed sequence tags (ESTs) have been generated from 585 clones randomly selected from a mixed-stage C. elegans cDNA library. Comparison of these ESTs with sequence databases identified 422 new C. elegans genes, of which 317 are not similar to any sequences in the database. Twenty-six new genes have been mapped by YAC clone hybridization. Members of several gene families, including cuticle collagens, GTP-binding proteins, and RNA helicases were discovered. Many of the new genes are similar to known or potential human disease genes, including CFTR and the LDL receptor. PMID- 1302007 TI - A novel GC-rich human macrosatellite VNTR in Xq24 is differentially methylated on active and inactive X chromosomes. AB - A new X chromosome-specific repetitive sequence, a 3 kilobase HindIII clone with a base composition of 63% C+G, has been isolated. The sequence is organized as a hypervariable tandem repeat cluster ranging in size from 150-350 kilobases, with outlying single copies. This locus, designated DXZ4 and mapped to chromosome band Xq24, may consist of as many as 50 variable-length alleles. It represents a class of variable number of tandem repeat polymorphism which may be termed 'macrosatellite'. The cluster is highly methylated on the active X chromosome and hypomethylated on the inactive X. PMID- 1302008 TI - Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development. AB - Denys-Drash syndrome is a rare human developmental disorder affecting the urogenital system and leading to renal failure, intersex disorders and Wilms' tumour. In this report, four individuals with this syndrome are described carrying germline point mutations in the Wilms' tumour suppressor gene, WT1. Three of these mutations were in the zinc finger domains of WT1. The fourth occurred within intron 9, preventing splicing at one of the alternatively chosen splice donor sites of exon 9 when assayed in vitro. These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development. PMID- 1302010 TI - From genetics to revelation? PMID- 1302009 TI - A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism. AB - Investigation of one kindred with autosomal recessive isolated hypoparathyroidism, which had resulted from a consanguineous marriage, has identified a g to c substitution in the first nucleotide of intron 2 of the parathyroid hormone (PTH) gene. This donor splice mutation could be detected by restriction enzyme cleavage with Ddel, and this revealed that the patients were homozygous for the mutant alleles, the unaffected relatives were heterozygous, and unrelated normals were homozygous for the wild type alleles. Defects in messenger RNA splicing were investigated by the detection of illegitimate transcription of the PTH gene in lymphoblastoid cells. The mutation resulted in exon skipping with a loss of exon 2, which encodes the initiation codon and the signal peptide, thereby causing parathyroid hormone deficiency. PMID- 1302011 TI - cDNA sequencing: a report from the worm front. PMID- 1302012 TI - Emerging patterns in genome organization. PMID- 1302013 TI - Dual developments in diabetes. PMID- 1302014 TI - Evolution of the mammalian G protein alpha subunit multigene family. AB - Heterotrimeric guanine nucleotide binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins. The multigene family of G protein alpha subunits, which interact with receptors and effectors, exhibit a high level of sequence diversity. In mammals, 15 G alpha subunit genes can be grouped by sequence and functional similarities into four classes. We have determined the murine chromosomal locations of all 15 G alpha subunit genes using an interspecific backcross derived from crosses of C57BL/6J and Mus spretus mice. These data, in combination with mapping studies in humans, have provided insight into the events responsible for generating the genetic diversity found in the mammalian alpha subunit genes and a framework for elucidating the role of the G alpha subunits in disease. PMID- 1302015 TI - Rescue of erythroid development in gene targeted GATA-1- mouse embryonic stem cells. AB - Development of definitive (fetal liver-derived) red cells is blocked by a targeted mutation in the gene encoding the transcription factor GATA-1. We used in vitro differentiation of GATA-1- mouse embryonic stem (ES) cells to reveal a requirement for GATA-1 during primitive (yolk sac-derived) erythropoiesis and to establish a rescue assay. We show that the block to development includes primitive, as well as definitive, erythroid cells and is complete at the level of globin RNA expression; that the introduction of a normal GATA-1 gene restores developmental potential both in vivo and in vitro; and that efficient rescue is dependent on a putative autoregulatory GATA-motif in the distal promoter. Use of in vitro differentiated ES cells bridges a gap between conventional approaches to gene function in cell lines and analysis of loss of function mutations in the whole animal. PMID- 1302016 TI - The Huntington's disease candidate region exhibits many different haplotypes. AB - Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180. PMID- 1302017 TI - Split verdict on schizophrenia. PMID- 1302018 TI - Fragile X founder effect? PMID- 1302019 TI - Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. AB - Macular degeneration is the most common cause of legal blindness in older patients in developed countries. Best's vitelliform dystrophy is an early-onset, autosomal dominant form of macular degeneration characterized by an egg-yolk-like collection of lipofuscin beneath the pigment epithelium of the retinal macula. Fifty-seven members of a five-generation family affected with this disease were studied. A combination of ophthalmoscopy and electro-oculography was used for diagnosis; 29 patients were found to be affected and 16 unaffected. Linkage analysis mapped the disease-causing gene to chromosome 11q13. Three markers in this region were found to be significantly linked (Zmax > 3.0) to the disease. Multipoint analysis yielded a maximum Lod score of 9.3 in the interval between markers INT2 and D11S871. PMID- 1302020 TI - Defective colour vision associated with a missense mutation in the human green visual pigment gene. AB - All red/green colour vision defects described so far have been associated with gross rearrangements within the red/green opsin gene array (Xq28). We now describe a male with severe deuteranomaly without such a rearrangement. A substitution of a highly conserved cysteine by arginine at position 203 in the green opsins presumably accounted for his colour vision defect. Surprisingly, this mutation was fairly common (2%) in the population but apparently was not always expressed. In analogy with nonexpression of some 5'green-red hybrid genes in persons with normal colour vision, we suggest that failure of manifestation occurs when the mutant gene is located at a distal (3') position among several green opsin genes. This mutation might also predispose to certain X-linked retinal dystrophies. PMID- 1302021 TI - Evidence of founder chromosomes in fragile X syndrome. AB - The mutation responsible for fragile X syndrome and myotonic dystrophy involves the amplification of a simple trinucleotide repeat sequence, which increases in successive generations of affected pedigrees accounting for increasing penetrance of both disorders. This common molecular basis suggests that the two diseases may share other genetic features, but whereas myotonic dystrophy exhibits a significant founder chromosome effect, fragile X syndrome apparently has a very high mutation frequency. By haplotype analysis of microsatellite markers which flank the fragile X unstable element, we have uncovered evidence of founder chromosomes of the fragile X 'mutation'. Disorders caused by heritable unstable elements may therefore exhibit common genetic properties including anticipation and founder chromosomes. PMID- 1302023 TI - Complete coverage of the Schizosaccharomyces pombe genome in yeast artificial chromosomes. AB - The genome of the fission yeast, Schizosaccharomyces pombe, consists of some 14 million base pairs of DNA contained in three chromosomes. On account of its excellent genetics we used it as a test system for a strategy designed to map mammalian chromosomes and genomes. Data obtained from hybridization fingerprinting established an ordered library of 1,248 yeast artificial chromosome clones with an average size of 535 kilobases. The clones fall into three contigs completely representing the three chromosomes of the organism. This work provides a high resolution physical and clone map of the genome, which has been related to available genetic and physical map information. PMID- 1302022 TI - Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs. AB - The mutation underlying myotonic dystrophy (DM) has been identified as an expansion of a polymorphic CTG-repeat in a gene encoding protein kinase activity. Brain and heart transcripts of the DM-kinase (DMR-B15) gene are subject to alternative RNA splicing in both human and mouse. The unstable [CTG]5-30 motif is found uniquely in humans, although the flanking nucleotides are also present in mouse. Characterization of the DM region of both species reveals another active gene (DMR-N9) in close proximity to the kinase gene. DMR-N9 transcripts, mainly expressed in brain and testis, possess a single, large open reading frame, but the function of its protein product is unknown. Clinical manifestation of DM may be caused by the expanded CTG-repeat compromising the (alternative) expression of DM-kinase or DMR-N9 proteins. PMID- 1302024 TI - Generation of region- and species-specific expressed gene probes from somatic cell hybrids. AB - Human genes expressed in interspecific somatic cell hybrids can be cloned specifically by subtractive cDNA hybridization. This approach is based on the observation that cDNA fragments from noncoding segments of mature human transcripts do not form stable heteroduplexes with their rodent homologues under high-stringency hybridization conditions. Thus, small, oligo-dT primed cDNAs from a rat/human hybrid retaining a fragment of human chromosome 17 were enriched for human sequences by hybridization with RNA from a sister clone containing a smaller human chromosome fragment. The enriched probe was used to screen a human cDNA library, and nine expressed genes from within the non-overlap region were obtained. This method should be useful for cloning active human genes from defined chromosome segments. PMID- 1302025 TI - Selection of a human chromosome 21 enriched YAC sub-library using a chromosome specific composite probe. AB - The subdivision of total genomic human yeast artificial chromosome (YAC) libraries into specific chromosome clone collections will greatly facilitate the construction of an integrated genetic, physical and transcriptional map of the genome. We report the isolation of 388 YAC clones from a human library with an average insert size of 620 kilobases (kb) by the hybridization of a composite chromosome 21 probe to a high-density array of YAC clones. Roughly half of these clones hybridize to chromosome 21 by fluorescence in situ hybridization. These clones represent a twofold coverage of the chromosome. The technique offers the potential of sub-dividing whole genomic YAC libraries into their chromosomal elements to produce high-resolution tools for genome mapping. PMID- 1302026 TI - The gene responsible for familial hypocalciuric hypercalcemia maps to chromosome 3q in four unrelated families. AB - Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant syndrome of unknown aetiology characterized by lifelong elevation in serum calcium concentration and low urinary calcium excretion. These features suggest that the causal gene is important for maintenance of extracellular calcium homeostasis by the parathyroid gland and kidney. To identify the chromosomal location of FHH gene(s), we clinically evaluated 114 individuals in four unrelated affected families and performed linkage analyses. The disease gene mapped to the long arm of chromosome 3 in each family (combined maximum multipoint lod score = 20.67). We suggest that this is the predominant FHH locus and anticipate that identification of the FHH gene will improve our understanding of the molecular basis for physiologic and pathologic regulation of calcium. PMID- 1302027 TI - DNA repair: two pieces of the puzzle. PMID- 1302028 TI - Breaking the blood barrier. PMID- 1302029 TI - BABI in dispute. PMID- 1302030 TI - The human PAX6 gene is mutated in two patients with aniridia. AB - Aniridia is an inherited ocular disorder of variable expressivity characterized by iris hypoplasia. A candidate aniridia gene, AN, which is the human homologue of the mouse Pax-6 gene, has recently been isolated by positional cloning from the WAGR region of 11p13. Here we describe mutations in this gene in two cases of sporadic aniridia, one detected at the DNA level and one at the RNA level, both of which are predicted to affect protein function. Mutations in Pax-6 have been described previously in Small eye, the proposed mouse model for aniridia. We present new phenotypic evidence for the validity of this mouse model. PMID- 1302031 TI - Kallmann syndrome due to a translocation resulting in an X/Y fusion gene. AB - The X-linked Kallmann syndrome gene was recently cloned and homologous sequences of unknown functional significance identified on the Y chromosome. We now describe a patient with Kallmann syndrome carrying an X;Y translocation resulting from abnormal pairing and precise recombination between the X-linked Kallmann syndrome gene and its homologue on the Y. The translocation created a recombinant, non-functional Kallmann syndrome gene identical to the normal X linked gene with the exception of the 3' end which is derived from the Y. Our findings indicate that the 3' portion of the Kallmann syndrome gene is essential for its function and cannot be substituted by the Y-derived homologous region, although a 'position' effect remains a formal possibility. PMID- 1302032 TI - Fragile X syndrome without CCG amplification has an FMR1 deletion. AB - We describe a patient with typical clinical features of the fragile X syndrome, but without cytogenetic expression of the fragile X or an amplified CCG trinucleotide repeat fragment. The patient has a previously uncharacterized submicroscopic deletion encompassing the CCG repeat, the entire FMR1 gene and about 2.5 megabases of flanking sequences. This finding confirms that the fragile X phenotype can exist, without amplification of the CCG repeat or cytogenetic expression of the fragile X, and that fragile X syndrome is a genetically homogeneous disorder involving FMR1. We also found random X-inactivation in the mother of the patient who was shown to be a carrier of this deletion. PMID- 1302033 TI - A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N terminus of beta-amyloid. AB - Mutations at codon 717 in exon 17 of the beta-amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co-segregates with the disease in two large (probably related) early-onset Alzheimer's disease families from Sweden. Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript. This mutation occurs at the amino terminal of beta-amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the beta-amyloid sequence. PMID- 1302034 TI - Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. AB - Replication deficient, recombinant adenovirus (Ad) vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in hepatocytes. In vitro, primary cultures of rat hepatocytes infected with a recombinant Ad containing a human alpha 1-antitrypsin cDNA (Ad-alpha 1AT) synthesized and secreted human alpha 1AT for 4 weeks. In rats, in vivo intraportal administration of a recombinant Ad containing the E. coli lacZ gene, was followed by expression of beta-galactosidase in hepatocytes 3 days after infection. Intraportal infusion of Ad-alpha 1AT produced detectable serum levels of human alpha 1AT for 4 weeks. Thus, targeted gene expression has been achieved in the liver, albeit at low levels, suggesting that adenovirus vectors may be a useful means for in vivo gene therapy in liver disorders. PMID- 1302035 TI - A methodological review of "method skeptic" reports. AB - The literature purporting to demonstrate that clinical neuropsychology is of limited validity in the forensic setting is reviewed critically and alternative interpretations are discussed. The methodological, procedural, conceptual, data analytical and survey/research design limitations are evaluated. PMID- 1302037 TI - Effects of ethanol, dexamethasone and RU 486 on expression of cytochromes P450 2B, 2E, 3A and glutathione transferase pi in a rat hepatoma cell line (Fao). AB - The aim of our study was to investigate the suitability of Fao cells, derived from the Reuber H35 rat hepatoma as a tool for studying regulation of drug metabolizing enzymes and drug metabolism. Fao cells express P450 2B, 2E, 3A and GST pi and were used to study the effects different inducers on these enzymes. Ethanol considerably increased the amounts of P450 2E and, to a lesser extent, P450 2B and GST pi mRNA and protein. Dexamethasone decreased the amounts of P450 2B, 3A and GST pi mRNAs, but had no appreciable effect per se upon the protein concentration of these enzymes. However, it antagonized the induction of P450 2E, 2B and GST pi by ethanol, even at the protein level. RU 486 decreased P450 2B protein and P450 2E mRNA and protein levels without effecting P450 3A and GST pi expression. RU 486 did not antagonize the dexamethasone effects, suggesting that at least some of these effects are not mediated by the glucocorticoid receptor. These data indicate that these cells constitute a suitable tool for studying the regulation of drug-metabolizing enzyme expression and drug metabolism. PMID- 1302039 TI - Clinical implications of variable antiarrhythmic drug metabolism. AB - Due to their narrow therapeutic indices, antiarrhythmic drugs have a great potential for adverse outcome. This is amplified by extreme inter-individual variability in their disposition and their pharmacological actions. Genetically determined inter-individual differences in metabolism account for a great deal of this variability. However, because of active metabolites, chirally-specific actions and chirally-specific metabolism, it is not possible to generalize about the outcome of phenotypic differences in the metabolism of a given drug. Careful study of these factors can enable physicians to understand the spectrum of potential responses to a drug. Newly developed molecular biology techniques now make it possible to determine the genotype for the CYP2D6 gene that controls metabolism of many antiarrhythmic drugs. This information, combined with a full understanding of the drugs' clinical pharmacology now makes it possible to predict the clinical outcome for drugs such as encainide, flecainide, mexiletine, propafenone and combinations of these drugs with quinidine. PMID- 1302038 TI - Deficient nifedipine oxidation: a rare inherited trait associated with cystic fibrosis kindreds. AB - Previous studies have indicated that there is weak genetic linkage between the defective gene in cystic fibrosis (CFTR) and the gene encoding the nifedipine metabolizing enzyme P4503A4 which are both located on chromosome 7. To examine further this possible association, nifedipine metabolism was investigated in a group of 59 volunteers, and 17 adult cystic fibrosis patients and 37 of their relatives. In agreement with the majority of previous studies, the volunteer group showed a unimodal distribution of recoveries for the major metabolite M-II ranging from 33 to 78% excretion in 8 h. In the case of both the cystic fibrosis patients and their parents, the distribution of recoveries was shifted to the left with five out of 20 parents and three out of 11 unrelated cystic fibrosis patients showing recoveries below the range observed in the volunteer group. This poor metabolism appeared to be both reproducible and heritable and did not appear to be a consequence of mutations in the CFTR gene. PMID- 1302036 TI - Alcohol, head injury, and neuropsychological function. AB - Evidence is reviewed indicating that the extent of alcohol abuse alone cannot account for the neuropsychological deficits observed in alcoholics, and that alcohol abuse and head injury may interact in some patients to influence neuropsychological status. Alcohol abuse both increases the risk for head trauma and potentiates the resulting brain injury, which can lead to negative neuropsychological consequences. Clinicians involved in the treatment of addiction should assess patients for history of head injury, and neuropsychological deficits consequent to both head injury and ethanol. These deficits may limit patient ability to comply with addiction rehabilitation programs. Conversely, clinicians in acute care and rehabilitation of the sequelae of head trauma should routinely assess their patients for substance abuse, because such abuse can have a significant impact on recovery from brain injury. PMID- 1302040 TI - Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects. AB - Twelve Caucasian healthy men and women, of whom six were poor metabolizers (PMs) and six were extensive metabolizers (EMs) of S-mephenytoin, together with 13 Chinese healthy men and women (five PMs and eight EMs), received a single oral 20 mg dose of omeprazole. Plasma levels of omeprazole and its two main metabolites, omeprazole sulphone and hydroxyomeprazole, were determined by HPLC. The mean (+/- SD) area under the plasma concentration-time curve (AUC) for omeprazole was 11.1 +/- 2.6 and 0.9 +/- 0.4 microM h in the Caucasian PMs and EMs, respectively. Corresponding values for elimination half-life were 2.3 +/- 0.4 and 0.7 +/- 0.4 h. In the Chinese PMs and EMs the AUC of omeprazole as 13.3 +/- 5.6 and 2.6 +/- 1.8 microM h. The AUCs of omeprazole were significantly higher in the Chinese EMs than in the Caucasian EMs possibly due to the higher proportion of heterozygotes in the former than in the latter group. The elimination half-life in the Chinese PMs and EMs was 2.4 +/- 0.2 and 0.8 +/- 0.2 h--similar to the observations in the Caucasian subjects. The maximum plasma concentration of hydroxyomeprazole was five-fold and four-fold higher in EMs compared to PMs among Caucasians and Chinese, respectively. The elimination half-life of the hydroxy metabolite was also longer in PMs than in EMs in both populations. The ratio between AUC for omeprazole and AUC for hydroxyomeprazole was 11.9 +/- 2.1 and 0.6 +/- 0.1 in Caucasian PMs and EMs, respectively. Corresponding values in the Chinese were 13.1 +/- 2.9 and 1.6 +/- 0.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302041 TI - Molecular characterization of the murine Coh locus: an amino acid difference at position 117 confers high and low coumarin 7-hydroxylase activity in P450coh. AB - Coumarin 7-hydroxylase (P450coh) and steroid 15 alpha-hydroxylase (P450(15 alpha) are encoded by members within the mouse 2A subfamily. Since P450coh activity is regulated by the Coh locus, we characterized P450coh cDNAs in strains having high coumarin 7-hydroxylase activity (CohH homozygote) including 129/J and DBA/2J, and compared them with P450coh cDNAs in low activity strains (CohL homozygote) C57BL/6J, C3H/HeJ and AKR/J. The nucleotide sequences of these two cDNAs differ by a single base, which results in an amino acid difference at position 117 (Val in P450cohH and Ala in P450cohL). The CohH phenotype exhibits approximately 10 fold greater Vmax and four-fold lower Km values than those in the CohL. Male 129 AKF1/J expresses approximately equal amounts of P450cohH and P450cohL mRNAs, associated with two Coh alleles. The levels of P450coh and P450(15 alpha) mRNAs in the F1 offspring suggested that a trans-acting factor(s) appeared to regulate the expressions of the P450 genes. A recent duplication in the ancestral mouse established the line of descent to P450(15 alpha) from the ancestral P450coh gene. During evolution, amino acid substitutions have selectively occurred at positions which alter the enzyme's substrate specificity and increase in the specific activity. Consistent with an important role of natural selection in the evolution of these genes is the relatively high nonsynonomous substitution rates on the P450(15 alpha) and the P450coh branches. As a result of these evolution events, the gene family consists of members which exhibit an extremely high degree of structural similarity, but very divergent hydroxylase activities and modes of regulation. PMID- 1302042 TI - Variability of acetaminophen metabolism in Caucasians and Orientals. AB - Acetaminophen (paracetamol) is extensively conjugated with glucuronic acid and sulfate prior to renal excretion. A minor metabolic route involves microsomal oxidation of acetaminophen to a hepatotoxic reactive intermediate, which subsequently undergoes glutathione (GSH) conjugation, yielding cysteine and mercapturate conjugates, both of which are excreted in the urine (Slattery et al., 1987). Data collected by de Morais et al. (1989) indicated that in comparison with normal subjects, glucuronidation of acetaminophen was impaired in subjects with Gilbert's syndrome, a genetically-based impairment of bilirubin glucuronidation. Thus, inter-subject and ethnic differences in acetaminophen disposition have pharmacogenetic and toxicological implications. This study was conceived to explore these differences. Urinary excretion of acetaminophen and its metabolites was observed in 125 Caucasian and 33 Oriental subjects. No appreciable difference was noted in the mean fraction of drug excreted as glucuronide between the two groups (51.5% in Caucasians vs 51.8% in Orientals). However, the data strongly indicated that the excretion of acetaminophen glucuronide was not normally distributed. Bimodality was apparent in both groups, with 20% of Caucasian and 33% of Oriental subjects displaying relatively extensive glucuronidation. In addition, glucuronidation displayed a strong negative correlation with sulfation (r = -0.97), suggesting the existence of a compensatory mechanism between the two metabolic pathways. The mean fractional excretions of cysteine and mercapturate conjugates did show significant differences between Caucasians and Orientals (p < 0.005). In addition, the ratio of mercapturate to total GSH-derived conjugates recovered appeared to be bimodal, indicating possible heterogeneity in the conversion of the cysteine conjugate to mercapturate via N-acetylation. PMID- 1302043 TI - Pharmacogenetics of alcohol metabolism and alcoholism. AB - The pharmacogenetic differences among individuals in their capacity to metabolize ingested alcohol are possibly responsible for the large inter-individual and inter-ethnic variations observed in the outcome of alcohol use and misuse. Based on results of adoption, twin, and family studies it is now widely accepted that the vulnerability to alcoholism is determined by genetic factors as well as by environment. There is a constant search for biological markers and specific genes which could identify individuals genetically predisposed to alcohol abuse and alcoholism. Numerous 'candidate genes' for alcoholism have been suggested including the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both ADH and ALDH exhibit genetic heterogeneity. An atypical form of ADH (ADH2), which contains a variant beta 2 subunit instead of the usual beta 1 subunit, differs substantially from the usual form in its kinetic properties and is found more frequently among the Japanese, Chinese and other Mongoloid populations than in Caucasoids and Negroids. A widely prevalent genetic polymorphism has been observed for ALDH; about 50% of Japanese and Chinese livers possess an inactive ALDH (ALDH2 isozyme) whereas none of the Caucasian or Negroid populations show this isozyme abnormality. These metabolic polymorphisms seem to contribute to differences in the in vivo elimination rate of ethanol and acetaldehyde, and may explain differences in alcohol-related behaviour and its disease outcome. Taken together, Orientals who possess an atypical ALDH2 gene are more sensitive to acute responses to alcohol, tend to be discouraged from drinking alcohol, and consequently are at lower risk of developing alcohol-related disorders. However, more work is needed to support these findings. Recent advances in molecular genetics have made it possible to analyze directly the human genome. This may help in a better understanding of the complex genetic and environmental factors in alcohol abuse by providing prospects for identification of gene loci which may be responsible for predisposition to, and protection from, alcoholism. PMID- 1302044 TI - Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA expressed human CYP1A2 and CYP2E1. AB - Six human cytochrome P450s expressed in HepG2 cells using vaccinia virus cDNA directed expression, were used to study the biotransformation of caffeine and its metabolites. CYP1A2 alone was responsible for caffeine 3-demethylation and paraxanthine 7-demethylation; in addition, 1A2 catalysed virtually all reactions related to caffeine and its metabolites. The metabolic profile of caffeine biotransformation by CYP1A2 averaged 81.5% for paraxanthine, 10.8% for theobromine and 5.4% for theophylline formation. It remained quite uniform when caffeine concentrations were varied. The most striking finding was that CYP2E1 (the ethanol-inducible form) had major influences upon caffeine metabolism: in particular, it catalysed the formation of theophylline and theobromine from caffeine. Thus, the in vivo metabolite profiling of caffeine may reveal CYP2E1 activities in addition to the previously documented activities of CYP1A2, polymorphic N-acetyltransferase and xanthine oxidase. PMID- 1302045 TI - Detection of human DNA mutations with nonradioactive, allele-specific oligonucleotide probes. AB - We describe a method of detecting human DNA mutations with nonradioactive, biotinylated allele-specific oligonucleotide probes. This method can detect seven different mutations in the butyrylcholinesterase, cystic fibrosis, and N acetyltransferase genes under identical assay conditions. This indicates that it may be used to detect mutations responsible for a wide variety of genetic diseases and pharmacogenetic conditions. The method involves first amplifying selected DNA fragments by the polymerase chain reaction and dot blotting the amplified DNA in duplicate onto small nitrocellulose squares. Each dot blot is then hybridized in individual wells containing a tetramethylammonium chloride solution with short biotinylated probes specific for either the normal or mutant allele. Successfully hybridized probes are detected by a simple colorimetric reaction using an avidin-alkaline phosphatase conjugate, which yields a very strong, clear signal. DNA from homozygous normal or mutant individuals hybridizes only to the normal- or mutant-specific probes respectively, while DNA from heterozygous individuals hybridizes equally well with both probes. These results can be easily interpreted to assign a genotype to the sample DNA. This method is amenable to automation, and may be useful in clinical laboratories for diagnosis of a wide variety of DNA mutations responsible for unusual reactions to drugs and environmental chemicals. PMID- 1302046 TI - Evidence for a dissociation in the control of sparteine, debrisoquine and metoprolol metabolism in Nigerians. AB - The 0-8 hour urinary distributions of the metabolic ratios of sparteine (100 mg), debrisoquine (10 mg) and metoprolol (100 mg) were measured in 165 healthy, unrelated, black Nigerian medical students. There was a weak correlation (rs = 0.51, p < 0.001; n = 82) between the metoprolol/alpha-hydroxymetoprolol (M/HM) and the sparteine/total (2- + 5-) dehydrosparteine (S/DHS) ratios. No significant correlations were found between the debrisoquine/4-hydroxydebrisoquine (D/HD) and M/HM ratios (rs = 0.16, n = 33) and between the D/HD and S/DHS ratios (rs = 0.31, n = 38). Both visual inspection and kernel density analysis of the data suggested the presence of two phenotypic groups for sparteine oxidation, with 4% of the population studied being putative poor metabolizers. In contrast biomodality was not apparent in the distribution of the log10M/HM and log10D/HD ratios. These findings provide evidence for a dissociation in the control of metoprolol, sparteine and debrisoquine oxidation in Nigerians and highlight the difficulties in the interpretation of data from pharmacogenetic studies in different ethnic groups. PMID- 1302047 TI - Characterization of a shoot-specific, GA3- and ABA-regulated gene from tomato. AB - A tomato (Lycopersicon esculentum) gene (GAST1) that encodes an RNA whose abundance increases > 20-fold in shoots of the GA-deficient gib1 mutant following spraying with GA3 has been characterized. An increase in GAST1 RNA levels is detectable 2 h after treatment and levels continue to increase for at least an additional 10 h. Between 12 and 24 h following treatment, the amount of GAST1 RNA begins to decline and at 48 h the level is nearly equivalent to that of water treated control plants. Nuclear runoff analysis indicates that 8 h after treatment with GA3, transcription of the GAST1 gene has increased only threefold, suggesting that GA acts both transcriptionally and post-transcriptionally. ABA partially inhibits the GA-mediated increase in GAST1 RNA abundance while ethephon, kinetin, and 2,4-D have little effect. GAST1 RNA is detectable in untreated leaves, stems, petioles and flowers, but not in roots. The GAST1 gene encodes a 0.7 kb transcript. The sequence of the GAST1 cDNA and genomic clones indicates that the gene is interrupted by three introns and potentially encodes a 112 amino acid protein of unknown function. PMID- 1302048 TI - Vicilin with carboxy-terminal KDEL is retained in the endoplasmic reticulum and accumulates to high levels in the leaves of transgenic plants. AB - Gene constructs were designed to test the effect of the endoplasmic reticulum (ER)-targeting signal, KDEL, on the level of accumulation of a foreign protein in transgenic plants. The gene for the pea seed protein vicilin was modified by the addition of a sequence coding for this tetrapeptide at its carboxyl terminus. The altered gene was placed under the control of a CaMV 35S promoter and its expression in the leaves of both tobacco and lucerne (alfalfa) was compared with that of an equivalent vicilin construct lacking the KDEL-coding sequence. The presence of the ER-targeting signal led to a greatly enhanced accumulation of the heterologous protein. In lucerne and tobacco leaves, the level of vicilin-KDEL protein was 20 and 100 times greater than that of the unmodified vicilin, respectively. These differences in expression level could not be explained by corresponding differences in the steady-state levels or the translatability of the mRNAs. However, when the stability of vicilin and vicilin-KDEL proteins was compared in their respective transgenic hosts, unmodified vicilin was found to be degraded with a half-life of 4.5 h while vicilin-KDEL was much more stable with a half-life of more than 48 h. Immunogold labelling of leaf tissues from transgenic lucerne and tobacco showed the presence of vicilin associated with large aggregates within the ER lumen of vicilin-KDEL plants. No such aggregates were detected in transgenic plants expressing wild-type vicilin. It is concluded that the carboxy-terminal KDEL caused the retention of the modified vicilin in the ER, and that this retention led to the increased stability and higher level of accumulation of vicilin-KDEL in leaves of transgenic plants. PMID- 1302049 TI - Characterization of cDNAs encoding two isoforms of granule-bound starch synthase which show differential expression in developing storage organs of pea and potato. AB - We have isolated cDNA clones to two isoforms of granule-bound starch synthase (GBSS) from pea embryos and potato tubers. The sequences of both isoforms are related to that of glycogen synthase from E. coli and one, GBSSI, is very similar to the waxy protein of maize and other species. In pea, GBSSII carries a novel 203-amino-acid domain at its N-terminus. Genes encoding both proteins are expressed during pea embryo development, but GBSSII is most highly expressed earlier in development than GBSSI. Similarly, GBSSI and GBSSII are differentially expressed in developing potato tubers. Expression of both isoforms is much lower in other organs of pea than in embryos. GBSSII is expressed in every organ tested while GBSSI is not expressed in roots, stipules or flowers. The possible consequences of this differential use of GBSS isoforms are discussed. PMID- 1302050 TI - A nuclear protein fraction binding to dA/dT-rich sequences upstream from the radish rDNA promoter [corrected]. AB - The external spacer (ES) of rRNA nuclear genes (rDNA) contains the sequences that control rDNA transcription initiation and enhancement. The ES is also characterized in most species by the presence of multiple repeated elements. In higher plants very few data are available on the cis- and trans-acting elements which control rDNA transcription. Using electrophoretic mobility shift assays (EMSA) it is shown that nuclear extracts from young radish leaves (NER) contain a protein fraction which binds to specific sequences in the radish ES. DNase I footprinting analysis allows mapping of the NER protein binding to dA/dT homopolymer stretches and to a 13-bp dA/dT-rich short repeat, found both in the seven approximately 100 bp repeat regions (located -1077 to -740 from transcription initiation site) and the region (-120 to -55) containing the putative promoter for rDNA transcription initiation. Whether this ES binding is due to a single or several different proteins is not known. So far, protein(s) binding to dA/dT-rich regions of a plant rDNA ES has not yet been described. Whether it is a specific RNA polymerase I transcription factor(s) or plays a more general role in genome expression remains to be elucidated. PMID- 1302051 TI - Maize C4 photosynthesis involves differential regulation of phosphoenolpyruvate carboxylase genes. AB - Maize as a C4 plant partitions CO2 fixation in two consecutive, spatially separated steps, thus eliminating photorespiration. The crucial enzyme for primary CO2 fixation is a C4-specific phosphoenolpyruvate carboxylase (PEPC). The differential expression of the unique C4-specific gene pepcZm1 and two non-C4 specific genes, pepcZm2A and pepcZm3B, in leaf, root, and stem is reported here. It is shown, in a transient homologous system, that this tissue-specific regulation is mainly controlled by their distinct promoters. The light induction of the C4-specific pepcZm1 in illuminated etiolated (greening) leaves probably relies on light-dependent developmental changes instead of an immediate responsiveness found for other maize genes. Analyses of deleted, mutated, and hybrid promoters revealed the redundant nature of a 14mer which is repeated four times and a decisive function of the TATA box-like motif, TATTT, and the sequences directly preceding it. No consensus sequences to other photosynthetic gene promoters were uncovered. Although light induces the expression of C4 PEPC and other photosynthetic genes in maize, this co-ordination is apparently mediated through different signal transduction pathways and distinct regulatory elements. This study indicates that the acquisition of a new promoter is at least partially responsible for the C4-specific expression of pepcZm1 essential for C4 photosynthesis. PMID- 1302052 TI - Late embryogenesis-abundant genes encoding proteins with different numbers of hydrophilic repeats are regulated differentially by abscisic acid and osmotic stress. AB - The late embryogenesis-abundant (Lea) genes, which are suggested to act as desiccation protectants during seed desiccation and in water-stressed seedlings, can be induced by abscisic acid (ABA) and various kinds of water-related stress. Using cotton Lea cDNAs as probes it was found that several of the Lea genes are conserved at the mRNA level in dicots and monocots. By screening a barley cDNA library with a cotton Lea D19 cDNA a family of three members was isolated. The putative B19 proteins have strong similarities to the Em protein in wheat and to LEA proteins from several dicots. However, the middle part of the B19 proteins consists of a 20-amino acid motif repeated three and four times in B19.3 and B19.4, respectively, but only once in B19.1. The gene products are strongly hydrophilic, the internal 20-amino acid motif being the most hydrophilic part. This motif is found once in cotton Lea D19 but is repeated twice in cotton Lea D132, indicating that the repeats are universal among monocot and dicot B19-like genes. The B19 genes are regulated similarly during embryo development, but to very different levels. In contrast, they are differentially regulated by ABA and various types of osmotic stress. In immature embryos all three genes are responsive to ABA and mannitol. However, B19.1 is also responsive to salt. Cold stress does not induce B19 mRNAs; only a stabilization of the transcript levels is seen. These results suggest that the responses to salt stress and exogenous ABA operate through different pathways. PMID- 1302053 TI - [The physiology of erection: study of the intrapenile tissue]. AB - The mechanisms which control erection depend on the integrity of the intrapenile smooth muscle fibres, the endothelium which lines them, and the thick membrane, the albuginea, which surrounds them. These dynamic structures are subject to neurological control which stimulates the release of neurotransmitters and neuromodulators. These substances exert synergistic and antagonistic effects and act via receptors which have been identified by means of pharmacological studies. The objective of this paper is to simply present the current state of knowledge concerning the physiology of the erectile tissue of the penis. PMID- 1302054 TI - [Role and contribution of karyotyping in male infertility]. AB - In the context of the aetiological investigation of male infertility, the authors stress the place and the contribution of blood karyotype testing in the light of their personal experience based on 1,612 subjects. This examination has an important place, as about 15% of azoospermic subjects and 6 to 7% of subjects with oligospermia less than 10 million spermatozoa per ml, either alone or in combination with other abnormalities of the semen examination, present a congenital chromosomal abnormality. A remarkable constancy of the results was observed according to identical recruitment criteria. The contribution of this examination is also important: the medical and psychological value of detecting the cause of azoospermia, genetic counselling and antenatal chromosomal diagnosis for non-azoospermic subjects with an equilibrated structural abnormality, in whom treatment allows a chance of procreation, genetic counselling for the family of these subjects in order to prevent the appearance of a chromosomally abnormal infant. In conclusion, the authors argue in favour of the routine use of this test in all infertile subjects with at least isolated oligospermia less than 10 million spermatozoa per ml. PMID- 1302055 TI - [Quantification of nucleolar organizers (NORs) in renal carcinomas. Comparison with the nuclear grade]. AB - Twenty three renal tumours: 6 clear cell carcinomas, 3 granular cell carcinomas, 8 mixed cell carcinomas, 3 tubulopapillary tumours, 2 spindle cell carcinomas and 1 oncocytoma, were retrospectively submitted to a staining technique which reveals argyrophilic proteins related to Nucleolar Organizer Regions (NORs). The semiautomated quantification of the number and mean surface area of the argyrophilic granules was performed by means of a quantimeter. The results were compared to the nuclear grade, which constitutes the reference histological prognostic factor. A very good correlation was observed between NORs and nuclear grade. The mean number of argyrophilic granules per nucleus (n) and more particularly their surface area (s) were very significantly increased in high grade carcinomas (n = 1.96), s = 3.72) in comparison with low-grade carcinomas (n = 1.50, s = 1.35). Quantification of NORs therefore allowed objective differentiation between a low nuclear grade and a high nuclear grade. The quantification method used emphasised the value of not only measuring the number but also the surface area of the argyrophilic granules. PMID- 1302056 TI - [Tumor ablation with focalized ultrasound. In vivo experiment with prostatic adenocarcinoma R3327 Mat-Ly-Lu]. AB - Ultrasound can induce tissue lesions by a combination of thermal and mechanical effects related to the tissue absorption of the energy emitted at the focal point of the transducer. The effects of focused ultrasound were studied in vivo in Fisher/Copenhagen hybrid rats bearing Dunning R3327 experimental prostatic carcinoma. The experimental tumour was transplanted by subcutaneous injection into the abdomen of 20 mg of tumour tissue derived from the Mat-Ly-Lu strain. Treatment was performed under general anaesthesia. The animal, maintained in a sarcophage exposing the tumour, was immersed in degassed water ensuring the interface between the tumour and the 1 MHz transducer. The displacements of the transducer were guided by computerised ultrasound screening, allowing irradiation of the entire tumour. The energy was supplied by a 7.5 kW amplifier in the form of series of impulses of variable duration. 77 rats were treated and the tumour growth was compared to that of non-irradiated control rats. Comparative series demonstrated the following results: 1. Immediate tumour destruction was obtained with a very high acoustic intensity (9,000 Watts/cm2) and a brief exposure time. 2. A transient slowing of the tumour growth rate was observed for an acoustic intensity of between 3,500 and 5,500 Watts/cm2. 3. Partial or total necrosis of the tumour was obtained with intensities of between 300 and 2,750 Watts/cm2 and a long exposure time. Total tumour destruction was obtained in 30 of the 49 rats treated under these conditions. 14 animals developed a local recurrence, 9 animals did not develop a local recurrence but developed metastases and 7 animals obtained long-term survival without local recurrence or metastasis. Under certain experimental conditions, focused ultrasound, without any adjuvant treatment, was able to destroy the Dunning R3327 Mat-Ly-Lu strain experimental tumour and, in certain cases, induced complete cure of this experimental cancer. PMID- 1302057 TI - [Is the lower urinary tract sensation different in patients with bladder instability?]. AB - The author examined the sensory innervation of the lower urinary tract in two ways: by evaluation perception of bladder fullness and by determining the perception threshold to electrical stimulation of the urethral and bladder wall. The results obtained in 95 patients with detrusor instability were compared to those of 312 patients with no neurological disease and a stable detrusor. Patients with detrusor instability reported sensations of fullness at statistically significantly lower volumes than patients with a stable detrusor. In contrast, the threshold of perception of electrical stimulation was the same in the two groups, which indicates that the sensory system involved in the perception of electrical stimulation is independent of motor function, while the sensation of fullness is influenced by detrusor motor activity. These results constitute additional evidence that perception of fullness and perception of electrical stimulation are related to two different pathways of afferent innervation. PMID- 1302058 TI - [Cyproterone acetate: cardiovascular tolerance]. AB - Cyproterone acetate, characterised by its antiandrogen and antigonadotrophin actions, is indicated in the treatment of advanced prostatic cancer. It can be used alone or in combination with surgical or chemical castration. This paper reviews the literature concerning the cardiovascular safety of this drug. Metabolic studies evaluating the impact of cyproterone acetate on lipids and certain clotting parameters indicate the absence of any harmful effects on these cardiovascular risk factors. The two trials conducted by the EORTC (30761 and 30 762) demonstrated that the cardiovascular safety of cyproterone acetate was better than that of diethylstilboestrol. Cardiovascular adverse effects were reported in less than 5% of cases. This figure was confirmed by a large number of published studies. A comparable incidence of cardiovascular complications was also observed in series of patients treated by orchidectomy, LHRH agonists and/or pure antiandrogens. It is difficult to formally demonstrate the responsibility of antihormonal treatment in this elderly population in which ischaemic heart disease and cerebral vascular accidents are frequent causes of death. PMID- 1302059 TI - [Value of tomodensitometry with injection and late images for the diagnosis of urinary leaks in kidney transplants]. AB - Between May 1985 and May 1990, 263 renal transplantations were performed in 254 patients, with 4 kidney-pancreas double grafts. 12 urinomas were observed, i.e. 4.56%. In one half of cases, clinical examination alone was able to establish the diagnosis of urinoma, but in the other 6 cases, complementary investigations were required. Post-contrast computed tomography with late images (between 6 and 24 hours after the injection) would appear to be the most useful investigation. Performed in 6 cases, this examination established the diagnosis of urinoma in 5 cases and also suggested the mechanism of the leak, which was always confirmed at operation. The positive diagnosis is based on extravasation of contrast agent which is clearly visible, even in the presence of low concentrations due to impaired renal function. This extravasation occurred early in 3 cases, but was delayed in 2 cases, emphasising the importance of late images. Other investigations appear to be less useful either because of a lack of sensitivity or because of imprecise anatomical information. The severity of urine leaks and the need for rapid treatment justify post-contrast computed tomography with late images in any case of suspected urinoma. PMID- 1302060 TI - [Vesico-ureteral reimplantation in kidney transplantation from living relative donor: extravesical or transvesical? Urologic complications and long-term results evaluation]. AB - Results of two techniques of ureteroneocystostomy were evaluated in a series of 400 consecutive living renal transplantations. In the first 150 patients (group A) PAQUIN ureteroneocystostomy was utilized and in the second 250 (group B) DE CAMPOS-FREIRE technique was performed. Significant urological complications were seen in 13 (8.6%) patients of group A and in 10 (4%) of group B. Bladder leak occurred in 5 patients of group A and in only 1 of group B (P < 0.05). Complications related to ureteral stenosis and ureteral necrosis were comparable in the two groups. High pressure vesicoureteral reflux was demonstrated in 2 of 85 patients of group A and in 15 of 160 of group B (P < 0.05). Abnormalities of intravenous urography were significantly higher in group A. The incidence of immediate and delayed post-transplant urinary infection was not statistically different among the two groups. We advocate the use of DE CAMPOS-FREIRE approach over the PAQUIN reimplantation, not only because of the marginal differences in the incidence of urological complications, but also because of the technical advantages offered by the former approach. PMID- 1302061 TI - [Bladder pheochromocytoma (report of a new case)]. AB - Bladder pheochromocytoma is a rare tumor. The authors report a new case and imaging modalities for localizing extrasurrenal pheochromocytomas are reviewed. PMID- 1302062 TI - [A case of bladder pheochromocytoma]. AB - Phaeochromocytoma is an endocrine neuroectodermal tumour usually located in the adrenal gland, but occasionally arising in other organs. The authors report a case of a vesical phaeochromocytoma presenting with haematuria. Radiological and endoscopic investigations revealed a right laterovesical submucosal tumour. Partial cystectomy was performed. The normality of the postoperative endocrine survey suggested disappearance of the tumour and absence of any other sites. PMID- 1302063 TI - [Cancer of the kidney mimicking renal multilocular cyst]. AB - Two cases of multilocular cystic adenocarcinoma of the kidney are presented. Although ultrasonography (US) and x-ray computed tomography (CT) are generally considered to be excellent diagnostic methods for renal cystic lesions, in the 2 cases reported here they failed to give the correct diagnosis. These unusual cases altered us to the possibility that the capabilities of modern diagnostic imaging techniques can lead to a false sense of security regarding the prognosis. To our knowledge, there are no reliable clinical features which distinguish multilocular cystic adenocarcinoma from multilocular cystic nephroma. PMID- 1302064 TI - [Leiomyosarcoma of the kidney]. AB - Leiomyosarcoma of the kidney is a rare neoplasm. Diagnosis is obtained by CT-Scan and immunohistochemical study. Radical nephrectomy is the only therapeutic way whose efficacity is known. The authors report a case of two localisations (kidney and bladder) of leiomyosarcoma. PMID- 1302065 TI - [A case of hemangiopericytoma of the pelvis]. AB - Haemangiopericytoma is an uncommon tumour of vascular origin. The authors report a case of one of the rarer sites of this tumour in man: paravesical pelvic haemangiopericytoma. Although modern imaging techniques have provided useful information concerning the hypervascular and clearly demarcated appearance of this tumour which displaces but does not invade adjacent organs, its diagnosis can only be established by histology. Its degree of malignancy and its invasive potential are unclear. The risk of local recurrence and metastases in more than one half of cases justifies wide surgical excision, possibly combined with adjuvant radiotherapy, and long-term follow-up. PMID- 1302066 TI - [Sarcoma of the spermatic cord. Report of 2 cases. Review of the literature]. AB - Illustrated by a case of rapidly fatal rhabdomyosarcoma in a child and a leiomyosarcoma in an adult, the authors differentiate the various histological types of sarcomas affecting the spermatic cord. Based on a review of the literature, they stress the great variety and various clinical courses related to the histological type. The predominant role of the histologist is stressed. The most widely used classifications are reviewed, leading to treatments in which primary surgery should be as complete as possible and combined with lymph node dissection or radiotherapy and chemotherapy. At the present time, the use of chemotherapy appears to be the decisive step in the improvement of the survival rates. The lymphophilic nature of rhabdomyosarcomas, which are embryonal in 95% of cases in children, can be schematically contrasted with the haematogenous nature of other sarcomas. The current approach to sarcomas of the spermatic cord, a minor site in comparison with the frequency of other soft tissue sarcomas, consists of an aggressive multidisciplinary treatment. PMID- 1302067 TI - [Transplantation of a horse-shoe kidney. Report of a case and review of the literature]. AB - The authors report a case of transplantation of a horseshoe kidney in two recipients. Based on this case and a review of the literature, they emphasise the technical precautions required for collection and transplantation of these malformed kidneys. PMID- 1302068 TI - [Isolated urethral injury following coital faux pas. Report of a case with no associated injury of the corpora cavernosa]. AB - An urethral lesion due to coital faux pas is usually associated with a lesion of the corpora cavernosa, but may occasionally be isolated. Suspected clinically due to the presence of urethral bleeding, the diagnosis of ruptured urethra is based on urethrography and, more importantly, urethroscopy, which appears to be more reliable for defining the complete or partial nature and the site of the rupture. Even in incomplete forms, surgical suture of the lesion appears to give better results than urinary diversion alone. PMID- 1302069 TI - [Portal hypertension: a rare cause of hematuria]. AB - A patient with undiagnosed cirrhosis presented with massive haematuria 16 years after augmentation colonoplasty. Portal hypertension (PHT) was responsible for a portocaval collateral circulation with vesical varices detected by low pressure endoscopy performed between episodes of haematuria. A very similar case was published in 1991. Surgical haemostatis with partial or total resection of the colonoplasty was only temporarily effective in our patient, who subsequently underwent liver transplantation due to repeated episodes of hepatic encephalopathy. No recurrence of haematuria was observed six years after the diversion. This rare cause of haematuria must be considered in view of the widespread use of intestinal conduits in urology: a dozen cases have been reported after transileal cutaneous ureterostomy, occurring an average of 3 years after the operation. Direct treatment of the varices, either by surgical devascularisation or resection or be endoscopic laser sclerosis or coagulation, is only temporarily effective. Treatment of the PHT appears to be the most effective measure in the long term: beta-blockers administered in the absence of episodes of haematuria or portal by-pass surgery in the case of failure. PMID- 1302070 TI - [Posterior epispadias with unknown complete duplicated urethra]. AB - The authors report a case of posterior epispadias associated with complete ventral urethra only discovered during the urethroplasty phase of the operation. This malformation is a rare form of urethral duplication and should be considered in any case of apparently isolated posterior epispadias. PMID- 1302071 TI - [Reconstruction of the penile skin in Fourier's gangrene: the use of a helical skin graft]. AB - The emergency treatment of Fournier's and perineal gangrene is now well defined and is based on excision of the necrotic tissues and broad spectrum antibiotics combined with hyperbarid oxygen therapy and symptomatic resuscitation measures. However, several procedures have been described for the reconstruction of the excised zones. In the light of one case of Fournier's gangrene, the authors evaluate reconstruction of the penile skin by means of a helical split-skin graft. With a follow-up of one year, the morphological and functional result was excellent. The patient has normal erection and the suture line does not contain any retractile adhesions. The authors therefore consider that this simple, but little known procedure should be part of the urologist's therapeutic arsenal for reconstruction of the penile skin. PMID- 1302072 TI - [Ureteral replacement with ileal graft with anti-reflux valve]. AB - The authors describe an ureteroileoplasty with a new anti-refluxing technique. A subtotal ureteroplasty is carried out, anti-refluxing proceeding is made. This one is based on Benchekroun's hydraulic valve principle. A transversal ileostomy is carried out 8 cm below the uretero-ileal anastomosis, which is invaginated and fixed to the proximal layer of the ileostomy with Dexon 3/0, the ileostomy is then closed using Dexon 2/0. The hydraulic valve may then ensure anti-reflux. PMID- 1302073 TI - [New findings on the physiology of erection or the concept of the active sponge]. AB - Until these last years, erection was mainly explained by neurovascular mechanisms. The erectile bodies were assimilated as a simple sponge passively filled or emptied by an unbalance between the arterial and venous flows. In fact, the erectile bodies themselves control the erection thanks to their potent smooth musculature. By contracting, they induce both flaccidity and detumescence, since their relaxation releases the erection. The erectile bodies work really as a kind of active sponge having the property to be autonomous and distortionable. However, the contractility of the erectile bodies cannot alone explain all the erection. This complex hydraulic process requires also complementary vascular mechanisms (cavernous outflow blockade, arteriodilatation) and tissular mechanisms (extrinsic compression of erectile striated muscles, specific distortion of each erectile body) under both hormonal and neuro-psychic control. By pointing up the fact that the active and passive tissue mechanisms play a major role for erection, this active sponge concept underlines the necessity for investigating the erectile tissues and allows to reconsider both physiopathology and treatment of dyserections. PMID- 1302075 TI - [Cutaneous trans-jejunal ureterostomy: an original technique used in 29 patients]. AB - The authors report an original technique of transintestinal cutaneous diversion using the jejunum A 10 to 15 cm segment of jejunum is raised from the second loop and is attached to the skin transperitoneally. The stoma lies below the ureterojejunal anastomosis and the two ureters, sutured according to Wallace's technique, are implanted end-to-end into the proximal and extraperitonealised end at the height of the sacral promontory. 29 patients have been treated by this technique for various indications: 21 bladder tumors, 5 neurogenic bladders, 1 bladder exstrophy, 1 cervical cancer, 1 prostatic cancer. 15 patients (52%) had previously received pelvic irradiation. The mean follow-up was 47 months (2-192 months) and the mortality was zero. 4 patients (13.8% developed early complications: 2 cases of urinary tract obstruction and 2 intestinal obstructions requiring 3 operations. 6 patients developed 7 minor late complications (24.1%): 2 cases of pyelonephritis, 4 cases of renal stones, only one of which required an operation, and 1 case of prolapsed stoma. None of the patients developed any alteration in renal function or dilatation of the upper urinary tract after the operation. The addition of sodium bicarbonate was found to be useless, as none of the patients developed any metabolic disorders. Transjejunal cutaneous ureterostomy achieves excellent drainage by means of a short graft with a stoma situated below the level of the ureteric implantation, as reflected by the absence of any long-term deterioration in renal function despite full lumen ureterojejunal implantation without an antireflux device. This technique is simple to perform and is indicated in all situations, particularly after pelvic irradiation. It is associated with low morbidity, no mortality and ensures an excellent long-term result. PMID- 1302076 TI - [Cholelithiasis and ileo-ceco-cystoplasty (study of 39 patients)]. AB - Limited data have been reported concerning the gallstone complications of ileocaecocystoplasty. A retrospective study of gallbladder ultrasonography looking for gallstones was performed in 35 of 39 patients undergoing ileocaecocystoplasty between July 1987 and July 1991. The surgical technique used in 33 men and 2 women with a mean age of 64.5 years was that described by Thuroff (Mainz Pouch). Gallbladder ultrasonography was performed a fortnight before the operation and then regularly during follow-up, with a mean follow-up of 24 months. Eight patients, an average of 13 months after ileocaecocystoplasty, developed ultrasonographically detectable gallstones, whose prevalence in the male study population was four times higher than that of the general male population. This study raises the question of whether cholecystectomy should be performed routinely during ileocaecocystoplasty and further studies should be conducted to clarify this problem. PMID- 1302074 TI - [Contribution of the ambulatory urodynamic monitoring to the study of micturition disorders]. AB - An outpatient urodynamic study allows simultaneous recording of bladder, urethral and abdominal pressures over a long duration with physiological bladder filling and under outpatient conditions. One hundred and eighteen outpatient urodynamic recordings were performed in patients presenting with disturbances of micturition such as urinary incontinence or dysuria. In the group of incontinent patients, the outpatient urodynamic recording was superior to the standard urodynamic assessment for the diagnosis of unstable bladder (p < 0.001). In the group of dysuric patients, the outpatient urodynamic recording allowed a precise evaluation of the detrusor activity and a simplified assessment of micturition. Its use combined with a urecholine test allows analysis of the onset, duration and intensity of action of the drug in comparison with a standard test. PMID- 1302077 TI - [Recurrence of lithiasis after extracorporeal lithotripsy, percutaneous surgery, and open surgery for calculi of the upper urinary tract]. AB - The safety and short-term effectiveness of percutaneous nephrolithotomy (PCNL) and extracorporeal shock wave lithotripsy (ESWL) have already been well established. However, long-term follow-up studies are essential to prove that the recurrence rate after PCNL and/or ESWL is equal or even better than that of surgery. We reviewed 57 patients treated with ESWL monotherapy, 45 patients treated by PCNL (or by PCNL combined with ESWL for complete staghorn stones) and 59 patients treated by open surgery who all had at least three years of follow up. The overall recurrence rate for ESWL was 37% for PCNL and for open surgery 39%. ESWL, PCNL and open surgery all showed a higher rate of recurrence and persistent bacteriuria when associated with residual stones. Therefore every effort should be made to remove residual fragments following stone treatment. We conclude that because of its efficacy and low morbidity ESWL should be the treatment of choice for most of renal calculi. Complete staghorn calculi are best treated with open surgery because the complete elimination of all calculous material and the eradication of infection are achieved at a higher rate than by PCNL and ESWL. PMID- 1302078 TI - [Piezoelectric extracorporeal lithotripsy in children: first results and reflections after 18 sessions]. AB - From 1988 to 1990, we treated 13 children between the ages of 2 and 15 years with stones of the upper urinary tract. These stones were treated by means of 18 sessions of piezoelectric extracorporeal lithotripsy: 14 under general anaesthesia and 4 without even any analgesia. We obtained an 84.5% success rate with no particular adverse effects. These results are similar to those reported for hydroelectric or electromagnetic shock wave lithotripsy, which are associated with a higher morbidity. The efficacy of extracorporeal lithotripsy in paediatrics is remarkable, but clinical studies in adults as well as animal experimentations have demonstrated severe renal contusion and do not formally exclude the possibility of delayed complications. At the present time, this technique should therefore be used very cautiously and must be accompanied by systematic prevention of recurrent stones. PMID- 1302079 TI - [Does magnetic resonance imaging allow the assessment of the loco-regional extension of cancer of the prostate? Report of 27 anatomo-radiologic comparisons]. AB - 27 patients with histologically proven prostatic carcinoma were investigated by magnetic resonance imaging (MRI) (0.5 Tesla) in order to determine the local spread of the cancer. These patients then underwent ilio-obturator lymph node dissection with frozen section examination, followed by radical prostatectomy. Histological examination of the resection specimens was performed on slides prepared from large transverse sections every 5 mn. The MRI examination was especially designed to confirm the diagnosis of capsular effraction based on the signals of the periprostatic fat (PF), periprostatic venous plexuses (PVP) and seminal vesicles (SV). An abnormality of at least one of these structures was considered to indicate the diagnosis of capsular effraction. The MRI data were compared to the histological findings. The results demonstrated a sensitivity of 62% for the PF signal, 52% for the PVP signal and 40% for the SV signal. The overall MRI-Histology correlation was found to be exact in 23 out of 27 cases (Accuracy = 85%). All of our four errors represented understaging (Sensitivity = 81%). When a rigorous methodology is respected, the high accuracy and sensitivity of MRI makes this modality an investigation of choice for the study of the prostatic capsule, as part of the routine staging of prostatic cancer. It should allow a better selection of patients with intracapsular cancer (T1-2), who constitute candidates for radical treatment. PMID- 1302080 TI - [Color doppler echography in the exploration of vasculogenic impotence]. AB - 102 patients with suspected vasculogenic impotence were evaluated with color doppler sonography. Measurement of normal systolic and diastolic velocities were obtained from the cavernosal arteries of patients responding by a full erection after intra-cavernosal injection of 20 mg of Papaverine. A correlation with cavernosometry was obtained in 61 patients and with selective internal pudendal arteriography in 11. The 10 patients with abnormal arteriograms had a systolic velocity < 25 cm/sec. 13 out of the 15 patients with an end diastolic velocity > 5 cm/sec had a venous leak defined by a maintenance flow rate of erection during cavernosometry > 25 ml/mn. End diastolic velocity is an excellent index of the function of the veno-occlusive system, provided the systolic velocity remains at a normal value. In case of arterial insufficiency, a diastolic flow < 5 cm/sec is of no value and cavernometry is mandatory to detect a mixed arterio-venous impotence. The addition of color doppler sonography permitted a more rapid detection of vessels and an easily reproducible measurement of velocities which makes color doppler sonography an excellent screening test for examining patients with potential vasculogenic impotence. PMID- 1302081 TI - [Electrophoretic study of the protein composition of human seminal vesicle secretion]. AB - The SDS-PAGE and two-dimensional reductived electrophoretic study of the liquid aspirated from human seminal vesicles showed that this medium contains high molecular weight proteins (greater than 150 kDa). In addition to these high molecular weight proteins, native seminal vesicle secretion is characterised by the presence of a large 47.4 kDa protein band corresponding to seminogelin, described by Lilja. The high molecular weight proteins actually correspond to associations of three types of protein subunits with molecular weights of 75-76, 63-64 and 47-48 kDa, which represent the structural elements of the coagulum; one of these subunits consists of seminogelin. Seminal vesicle secretion contains very little or no proteolytic enzymes, so that its protein composition remains stable even after incubation for 24 hours. PMID- 1302082 TI - [Urinoma: a complication of celiac plexus infiltration]. AB - A case is described in which a major complication resulted from this technique. We have found no previous record of urinoma due to infiltration of a caustic agent. PMID- 1302083 TI - [Endo-urologic treatment of ureteral fistulas occurring after pelvic surgery for carcinoma: report of 5 cases]. AB - The authors report 5 cases of ureteric fistula after radical pelvic cancer surgery. Three patients had a recurrent tumour and 3 had received radiotherapy. Endourological methods achieved 4 immediately satisfactory results, but only one complete long-term success. Isolated percutaneous drainage of the pyelocaliceal cavities effectively dried up the urine leak, but carried a high risk of secondary stenosis of the excretory tract in the absence of concomitant intubation of the fistula zone. However, endourological treatment, combined with urinary diversion and catheterisation of the pathological ureter, represented a reliable alternative to conventional surgery. PMID- 1302084 TI - [Postoperative rectoprostatic fistulas. Report of 2 cases. Review of the literature]. AB - The authors report two cases of acquired prostatorectal fistulae after TURP, which were treated by a Kraske approach. They review the literature of iatrogenic fistulae and all of the techniques of approaching the prostatorectal region. If the bladder drainage is always necessary and may be sufficient in as much as 34% of the patients, the need for a colostomy and the choice of the approach is discussed. PMID- 1302085 TI - [Pyeloureteral lieberkuhn adenocarcinoma after trans-intestinal ureterostomy for bladder exstrophy]. AB - The authors report a case of pyeloureteric adenocarcinoma in a urinary diversion inserted for bladder exstrophy and in a context of chronic pyelonephritis secondary to renal stones. The various aetiopathogenic hypotheses are discussed. Renal stones and chronic inflammation very probably played an important role in the development of this type of adenocarcinoma in the urothelium. PMID- 1302086 TI - [Burkitt's lymphoma: an exceptional cause of testicular tumor]. AB - Based on a case of Burkitt's lymphoma presenting in the form of a testicular mass in a 66 year old man, the authors stress the importance of making the diagnosis as early as possible. This malignant lesion has one of the greatest capacities for proliferation and any delay in treatment can decrease the chances of curability of the tumour. PMID- 1302087 TI - [A rare psychogenic anejaculation. Report of a case of prolactin adenoma]. AB - The authors report a case of prolactinoma discovered during assessment of a case of ejaculation failure attributed for more than eight years to a psychogenic cause. Because of the size of the tumour, surgical resection of the lesion left a persistent hyperprolactinaemia, which only returned to normal after treatment with bromocriptine. The persistence of sexual disorders justified adjuvant treatment with exogenous testosterone. Despite the unusual mode of presentation of hyperprolactinaemia, these data correspond to those reported in the literature. Prolactin assay should therefore be performed in any case of male sexual dysfunction to allow the early diagnosis of prolactinoma and to improve the functional prognosis. PMID- 1302088 TI - [Anterior sacral meningocele with urologic manifestations. Report of 3 cases]. AB - Anterior sacral meningocele is defined as a spinal fluid-filled thecal sac in the pelvis communicating with the spinal subarachnoid space through a defect in the anterior sacral wall. Since scimitar shape of the sacrum is characteristic, diagnosis is easily confirmed by echography and myelography. The sac very often contains benign tumors and a thickened filum terminale which can achieve a tethered cord syndrome. This congenital malformation, whose autosomal inherited condition has been proposed, has usually few characteristic symptoms but can present itself as a neurogenic bladder from tethered cord origin. Neurosurgical treatment can prevent rupture of the meningocele with meningitis. In addition to symptomatic treatment of the neurogenic bladder, the urologist must advise neurosurgical operation to preserve potency and cure specific bladder dysfunction secondary to tethered cord syndrome. PMID- 1302089 TI - [The Bourne's test: a relevant contribution to the diagnosis of vesico-enteric fistulas]. AB - Diagnostic verification of vesicoenteric fistulae is necessary in order to establish the indication for surgical therapy, but this is frequently difficult. This is because uroradiological and endoscopic methods are unreliable and the symptoms are often nonspecific. The Bourne test is a simple noninvasive screening method. If necessary, it can be supplemented by computer tomography. The problems are discussed with reference to a case report. PMID- 1302090 TI - [Microsurgical vaso-vasostomy: a reliable method of vasectomy reversal]. AB - An original microsurgical technique has been used since 1971 to reverse the vasectomies of 2,110 men. Both sides were anastomosed if possible using a meticulous two layered technique with further reinforcing sutures to prevent strain on the join. Other important points include testing the fluid emerging from the testicular end, checking patency of the prostatic end and insisting on good scrotal support in the recovery phase, particularly the important first few days. The series returned a 95% baby rate, with a return of sperm to the ejaculate in 93% of cases. PMID- 1302091 TI - [Complications of prostatic biopsies. Analysis of a series of 4,764 biopsies]. AB - A multicentre, retrospective series of 4,764 prostatic biopsies revealed 89 complications (1.86%). The commonest complications were infectious (including 10 cases of septicaemia) and antibiotic prophylaxis does not appear to be able to totally prevent them. Thirty three complications occurred after negative biopsies. Many minor complications are probably treated at home by the local doctor and would therefore not be reported to the urologist. PMID- 1302092 TI - [What is new in the diagnosis of tumors of the testis?]. AB - The major new developments in the diagnosis of testicular tumours over the last 11 years consist of imaging techniques and tumour markers. Doubtful clinical diagnoses of testicular tumours can now be clarified as a result of progress and diffusion of ultrasonography. Ultrasonography, a reliable (90%) and non-invasive examination, is more of a diagnostic aid than a decisive element, except in a few special cases. At the present time, magnetic resonance imaging is of no value in the diagnosis of testicular tumours. Alpha-foetoprotein and human chorionic gonadotrophin are the two essential markers for the follow-up, rather than for the diagnosis, of a testicular tumour. Lactate dehydrogenase and placental alkaline phosphatase are useful, especially in the seminomas, but are much less specific. The other markers studied have either not proven to be of any clinical value or are still in the field of research. Computed tomography appears to be gradually replacing lymphography for lymph node staging. The combination of the two examinations reduces the number of false negatives (10%) at the price of a higher number of false positives (38%). The diagnosis of testicular cancer can sometimes be made at the stage of carcinoma in situ, a precancerous lesion which progresses towards an invasive tumour in one half of cases. The practical indications for screening for carcinoma in situ are still controversial. PMID- 1302093 TI - [Intracavernous injections]. AB - Virag's paper concerning erection induced by intracavernous injection of papaverine was published 10 years ago, in 1982. Since this time, several substances have been tested; some have been abandoned, while others have demonstrated their efficacy and relative safety. After briefly recalling the physiology of erection and the principal substances used (papaverine, phentolamine, moxisylyte, PGE1, ceritine and VIP), the indications for intracavernous injection are reviewed in the context of investigation and treatment of certain forms of impotence. Lastly, the injection technique, the results and the complications are discussed, with emphasis on the ways to prevent or treat these complications. PMID- 1302094 TI - [The molecular basis of tumor progression in prostatic cancer]. PMID- 1302095 TI - [100 percutaneous endopyelotomies. Technique, indications, results]. AB - 100 percutaneous endopyelotomies were performed in 95 patients from October 1985 to February 1991 to treat 46 cases of acquired stenosis and 54 cases of congenital hydronephrosis. The acquired stenoses were treated by scalpel incision, while the congenital hydronephrosis were generally treated by electrocautery. The evaluable results for 81 ureteric units with a mean follow-up of 37 months showed an overall success rate of 84%. No significant difference in the results was observed in relation to the patient's age, the technique used or the stage of the hydronephrosis (81% success rate): the results in the treatment of congenital hydronephrosis (86%) are slightly inferior to the results of surgical pyeloplasty. PMID- 1302096 TI - [First clinical experience with extracorporeal lithotriptor EDAP LT.02]. AB - A preliminary study of the EDAP LT.02 extracorporeal lithotriptor is presented. The apparatus includes a double isocentric detection system (ultrasonographic and radiological), facilitating the in situ treatment of ureteric stones. Seventy patients with a total of 89 urinary stones were treated by primary extracorporeal lithotripsy (ECL) with no preliminary selection. 69 stones (77.5%) were located in the kidney and 20 stones (22.5%) were situated in the ureter. Anaesthesia was only required in 2 cases. The patients received an average of 1.2 lithotripsy sessions. Out of the 70 patients treated, there were 46 (66%) complete successes, 12 (17%) partial successes and 12 (17%) failures [corrected]. PMID- 1302097 TI - [Correlation between chemical composition, density, and results of extracorporal lithotripsy in renal and ureteral lumbar calculi]. AB - Based on a series of 388 patients with a total of 466 renal and lumbar ureteric stones (414 kidneys) treated between 1987 and 1990 by extracorporeal shock wave lithotripsy (ESWL) using the SONOLITH 3000* apparatus, the authors analyse the indications and results criteria for ESWL. The success criteria adopted excluded any residual fragment and considered patients lost to follow-up as failures. The success rate varied between 48.3% and 73.8% when residual fragments less than 5 mm were included and when drop-outs were excluded. A correlation was established between the radiographic appearance of the stone (dense, smooth, spiculated), its predominant spectrophometric nature and the results of ESWL: low density, spiculated Weddellite (WD) stones gave good results and very dense, smooth Whewellite (WW) stones gave less favourable results. The authors propose a refinement of the indications for ESWL in order to improve the results. Predominantly WW stones may be suitable for primary percutaneous nephrolithotomy. PMID- 1302098 TI - [Cost-effectiveness analysis of extracorporeal lithotripsy]. AB - The recent introduction of extracorporeal lithotripsy (ECL) for the treatment of urinary stones has raised new questions for doctors and economic policy decision makers. This study presents a cost-effectiveness analysis of extracorporeal lithotripsy conducted in an Italian hospital which has used a Sonolith 3000 lithotriptor since 1989. The overall cost of treatment by ECL (of a simple case of urinary stones) is 5,080 FF and the cost per cured case (taking into account the number of sessions per patient and the percentage of cured cases) varies between 6,200 FF and 9,500 FF. The results obtained (influenced by the lack of certain clinical data due to the recent use of this technique) appear to be in favour of extension of ECL treatments in comparison with surgical treatment due to their lower cost, lower morbidity and shorter convalescent period. PMID- 1302099 TI - [Endo-surgical dissection of the upper urinary tract through the retroperitoneal and transperitoneal route: an experimental study with pigs and cadavers]. AB - In order to define the best method for endosurgical dissection of the upper urinary tract, an experimental study comparing the retroperitoneal and transperitoneal approaches was performed. Between September 1991 and February 1992, 15 female pigs and 8 human cadavres underwent endosurgical dissection of the upper urinary tract. The retroperitoneal approach was used in 8 pigs and 5 cadavres. In the lateral supine position, the retroperitoneum was insufflated at the lower pole of the kidney, via a 2 cm cutaneo-muscular incision, followed by a blind dissection with the finger to create a space in the retroperitoneal fat. Four trocars were inserted into the retroperitoneal space allowing dissection of the ureter, kidney and its vascular pedicle. The renal vessels and the ureter were then clipped or stapled with the endo-GIA then sectioned. The operation was successfully performed in all of the pigs with a mean operating time of 2 hours. Complications were limited to two peritoneal effractions. Retroperitoneal endosurgical dissection was much longer and more difficult to perform on the cadavre (mean operating time: 3 hours). Satisfactory retropneumoperitoneum was never able to be obtained due to the large amount of retroperitoneal fat and the proximity of the twelfth rib and posterior iliac crest interfered with the insertion of the trocars and made dissection more difficult. The transperitoneal approach was performed in 7 pigs and three cadavres. In the lateral supine position, after creating pneumoperitoneum using a Veress needle, 4 trocars were inserted into the peritoneal cavity. Toldt's fascia was gripped and incised allowing retraction of the colon towards the midline, thereby exposing the renal region. The ureter and the renal vessels were dissected. The renal artery and vein were then clipped or stapled with the endo-GIA then sectioned, while the ureter was clipped and sectioned. The complications of the transperitoneal route were: an injury to the small intestine during insertion of a trocar and haemorrhage due to accidental section of a lower pole renal artery, which was able to be controlled by application of clips. In the pig, the transperitoneal approach was as simple to perform as the retroperitoneal approach and the mean operating time was the same (two hours).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302100 TI - [Flow cytometry in bladder lavage fluid for the diagnosis and surveillance of bladder tumors. Preliminary results]. AB - The authors evaluate the accuracy and practical applications of flow cytometry (FCM) on bladder lavage fluid in the diagnosis and follow-up of bladder tumours. The apparatus used was a Coultronics Epics Profile II cytofluorograph. Two hundred and fifteen samples were obtained with a yield of 86%. The specimens were preserved in ethanol. The staining was performed on whole cells with preservation of the cytoplasm. The analysis of a control group of 45 patients confirmed that the FCM study of ploidy was specific (0.97 for normal bladders and 0.8 for inflammatory lesions). Four aspects were evaluated: Correlation between FCM and the histological type of the tumour: a significant difference was observed between the control group, the invasive tumour group (p < 0.01) and the carcinoma in situ group (< 0.001). A significant difference was observed in the case of high-grade PTA and PT1 tumours. No significant difference was observed between FCM and classical cytodiagnosis when this technique was performed by a trained cytologist. Predictive value of FCM for the recurrence of PTA and PT1 tumours: 40 patients were followed with a mean follow-up of 13 months. The relative risk of recurrence in the case of a tumour with an abnormal FCM was 2 (p < 0.05). FCM and monitoring of conservatively treated tumours: 30 patients with normal endoscopic examination after endoscopic resection of a PTA or PT1 tumour underwent cytometric analysis and cytodiagnosis. In the case of an abnormality on cytometry, randomised bladder biopsies and urography were performed. The positive predictive value for the presence of a lesion not diagnosed by cystoscopy and detected by FCM was 0.38 +/- 0.26. FCM and intravesical chemotherapy: 16 patients with PT1 tumours and abnormal FCM received BCG therapy (11 patients) or mitomycin C instillations (5 patients). A significant difference (p < 0.01) was observed between the 2 treatments in terms of normalisation of cytometry.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302101 TI - [Continent urinary diversion with the Florida pouch]. AB - Continent urinary diversion (Florida Pouch) has been performed on 151 patients. The surgical technique utilizes a detubularized extended right colon segment, a doubly-plicated segment of ileum and a non-tunneled uretero-intestinal anastomosis. Mortality rate was 1.3%. Early and late complication rates have been minimal. 2.8% were incontinent. No radiographic renal damage has been noted and electrolyte abnormalities have not been a problem. The procedure is highly recommended to those surgeons performing continent urinary diversions. PMID- 1302102 TI - [Endoscopic internal urethrotomy. Retrospective studies of 132 cases]. AB - The authors report a series of 132 patients with urethral stricture all treated by the same surgical technique between 1979 and 1984: direct vision internal urethrotomy. 62% of good results were obtained after a single operation with a follow-up ranging between 18 months and 5 years. There was no mortality and the morbidity was considered to be 5%. The authors indicate that the results were more favourable when the operation was performed in a solitary, short (less than 2 cm) non-infected stricture of the proximal urethra. The duration of postoperative catheterization was 10 days; catheterization for a longer period did not provide any significant advantage. The poor results (38%) were reported in cases of extensive strictures situated in the distal urethra or in patients with a history of urethral surgery. These cases were treated by repeated internal urethrotomy; 32% were cured after a second urethrotomy, while the others required maintenance sessions of urethral dilatation or even a urethroplasty procedure. PMID- 1302103 TI - [Scrotal trauma. Report of 33 cases]. AB - We report a serial case study of 33 patients from May 1980 to November 1990 presenting a scrotal contusion. In 2/3 of cases, the physical examination showed a scrotal oedema or an hematocele. Ultrasonography showed a testicular injury while clinical examination was subnormal in 2 patients. In the other cases, ultrasonography showed an hematocele without asserting in all cases the traumatic rupture of the tunica albuginea. 27 patients have been surgically explored: 14 ruptures of the testicle, 3 intratesticular haematoma, 3 scrotal open traumatic injuries, and 7 extratesticular haematoma. Only 3 orchidectomies were required for the 6 patients who have not been explored surgically, the testis was normal at one month. The follow-up of these young patients is difficult, 11 had been seen again at 1 month. At long term follow-up, three patients had been seen at 1, 3 or 6 years without testicular after-effects. PMID- 1302104 TI - [Impotence in pelvic fractures. Report of 16 cases]. AB - The authors study impotence secondary to a pelvic fracture on the basis of a retrospective series of 16 cases. All these patients had a lesion of the membranous urethra and seven of them underwent a deferred emergency urethral repair. Although the constancy of the urethral lesion is probably related to the fact that this series was recruited from a urology department, impotence is classically considered to be more frequent in the presence of a urethral lesion than in the absence of such a lesion. Two patients presented with incomplete impotence and fourteen with complete impotence. Ten of these sixteen patients spontaneously regained satisfactory erections. When erections were not obtained, the authors analysed the various therapeutic possibilities available, stressing the arterial factor which is usually insufficiently investigated. PMID- 1302105 TI - [What can be expected from the ligation of the deep dorsal vein of the penis in the treatment of caverno-venous impotence? Report of a series of 21 cases]. AB - 21 patients with venous vasculogenic impotence were treated by ligation of the dorsal vein of the penis. 71% of the patients were improved after 8 months, but only 53% were still improved after 25 months. However, this simple operation can be proposed palliatively to patients selected on the basis of cavernosometry, in combination with other medical treatments. PMID- 1302106 TI - [Prostatic involvement in leukemia. Report of a case]. AB - Infiltration of the prostate is frequent in the course of leukaemia. It is usually asymptomatic or may present in the form of classical bladder neck obstruction. The diagnosis is generally established during investigation of benign prostatic hypertrophy by biopsy or during treatment by resection. Treatment of leukaemia by systemic chemotherapy is unable to sterilize the prostatic site and must therefore be combined with local radiotherapy. PMID- 1302107 TI - [Management of incidentalomas]. AB - An incidentaloma is defined by the exclusion of other lesions, primarily phaeochromocytomas, by means of MRI and metanephrine and normetanephrine assays, followed by other secreting tumours by means of clinical examination and limited laboratory assays (potassium, cortisol, aldosterone). Tumours which need to be operated because of the risk of (malignant) adrenal cortical tumour can be distinguished from radiological adrenal anomalies which simply need to be monitored on the basis of the initial size of the lesion or its rate of growth on repeated CT scans. PMID- 1302108 TI - [Value of intravesically instilled oxybutynin in refractory bladder hyperactivity. Study of 15 cases]. AB - 15 patients with neurogenic detrusor hyperactivity refractory to oral anticholinergics received a daily intravesical instillation of 5 mg of oxybutinin for 6 days. An improvement was observed clinically in 10 cases and on urodynamic parameters (60% increase in bladder capacity, doubling of the volume inducing an urge to void) in 12 cases. The mechanism of action is discussed. PMID- 1302109 TI - [Treatment of bladder instability with interferential current. Report of 20 cases: preliminary results]. AB - 20 patients with unstable bladder unresponsive to medical treatment by anticholinergics were treated by interferential current retraining stimulations. This technique combines the advantages of retraining stimulation with external application. Each patient received 6 to 20 stimulation sessions at a rate of one per week in children and two per week in adults. 18 patients were clinically and urodynamically improved with resolution of incontinence and the follow up urodynamic assessment showed return of normal bladder volume and tone. No adverse effects were observed. No recurrences of the symptoms were observed with a mean follow-up of 18 months. The authors believe that this reliable technique constitutes an alternative to other retraining stimulation methods. PMID- 1302110 TI - [The combination of oral trazodone-moxisylyte: diagnostic and therapeutic value in impotence. Report of 110 cases]. AB - An oral drug treatment was prescribed systematically for one month in 110 unselected patients suffering from impotence: Tradozone (75 mg/day)+Moxisylite (180 mg/day) daily, or at higher doses if possible, and Trazodone (25 mg/day)+Moxisylite (60 mg/day) one hour before any sexual intercourse. Adverse effects were uncommon (6.3%). Satisfactory sexual activity was restored in 28% of cases and an improvement in spontaneous erections was obtained in 42% of cases. No improvement was observed in 30% of cases. This oral drug test therefore presents 3 advantages: a) it facilitates the diagnosis and treatment of impotence by eliminating moderate forms of psychogenic impotence, b) it reduces both the morbidity and cost of investigation of impotence by reducing the number of tests performed, c) it emphasizes the role of oral treatment in impotence. In conclusion, this oral drug test should be used because of its simplicity, safety and real efficacy. The current objectives of this test are to improve the efficacy of oral treatment as a result of pharmacological progress. PMID- 1302111 TI - [Precancerous conditions of the prostate]. AB - Carcinoma in situ, dysplasia, prostatic intra-epithelial neoplasia, duct-acinar dysplasia and large-acinar hyperplasia are various terms describing more or less identical forms of prostatic epithelial atypia. The precancerous nature of these lesions can be demonstrated by: morphological and functional similarities with carcinoma, a younger age than that of carcinoma, a higher incidence in cancerous prostates, an identical zonal distribution and a significant progression of high grade lesions towards carcinoma. These hypoechoic lesions can be detected or monitored by transrectal ultrasonography. They also secrete PSA at levels intermediate between those of benign prostate and adenocarcinoma. Because of the occasional risk of malignant transformation and a frequent association with carcinoma, these lesions should be regularly monitored by digital rectal examination, PSA assays and possibly by ultrasound-guided biopsies. PMID- 1302112 TI - [Carcinoma in situ of the testis]. AB - Carcinoma in situ (C.I.S.) of the testis is the only known precancerous lesion of germ cell tumours. The prevalence and the incidence of C.I.S. are both unknown, although predisposing factors have been identified: history of germ cell tumour of the contralateral testis, cryptorchidism or history of ectopic testis, decreased fertility or sterility. The incidence is higher in the presence of a combination of several of these factors. No complementary investigations have been demonstrated to be of any value in the detection of C.I.S. which can only be diagnosed, at the present time, by means of surgical biopsy. Once C.I.C. has developed, it never resolves spontaneously. In one half of cases the C.I.S. evolves into an invasive tumour over a period of 5 years. There is no consensus concerning the population in which testicular biopsy should be proposed looking for C.I.S. A large scale C.I.S. screening and detection programme has been proposed in Denmark. However, it is not clear that there is any major gain in testicular cancer morbidity and mortality in comparison with a surveillance programme of patients at risk. Apart from conservative follow-up, two types of treatment can be proposed: orchidectomy or external beam radiotherapy which appears to eradicate the C.I.S. while preserving endocrine function. PMID- 1302113 TI - [Hippocrates: a great prophet in scientific andrology]. PMID- 1302114 TI - [Treatment of post-partum urogenital fistulas in Africa. 261 cases observed in 10 years]. AB - A homogeneous series of 261 post-partum urogenital fistulae treated over the last ten years in Africa by the same operator is analysed. Mostly occurring in young, primiparous women in a rural environment, the predominant cause was neglected dystocic delivery in the bush (65.5%). The fistula was traumatic in 27.9% of cases and secondary to hysterectomy in 6.8%. 247 patients underwent surgical repair. The choice of repair procedure, generally performed via the transvaginal route (92.3%), was based on the anatomical classification of the various lesions into three groups of indications: Group I: simple fistulae (98), in which surgical treatment consisted of closing the fistula orifice by simple separate suture of the bladder and vagina, generally followed by success. Group II: more difficult fistulae (109) with severe tissue damage, raising the dual problem of continence and healing and requiring the use of mattressing with a well vascularised adjacent tissue (55 cases). Group III: complicated fistulae (54) with the presence of associated lesions, often requiring multiple urological, genital and intestinal operations as well as complementary plastic techniques (31 cases): double autoplasty of the labia major (17) and adipocutaneous pedicle skin flap (14). 212 of the 261 patients (81.2%) were cured, 23 obtained partial cure (insufficient continence, amenorrhoea, vaginal sclerosis making sexual activity impossible) and there were 26 failures. Urinary diversion was the only solution in 14 patients (7.8%). The objective in surgical correction of urogenital fistulae is twofold: to obtain good quality cure (81.2%), i.e. controlled micturition and a normal, genital, conjugal and social life. overcome the limitations of palliative operations which are always poorly accepted in Africa, at the cost of repeated, staged surgery designed to simplify the lesions in the most severely damaged cases. Prevention programmes designed to eradicate urogenital fistulae, which constitutes a real public health problem in developing countries, will only be made credible by an improvement in the quality of the results obtained in the treatment of this disease. PMID- 1302115 TI - [Uretero-rectal diversion with rectal enlargement. Clinical results]. AB - In some patients, after total cystectomy, the urethra cannot be used, preventing the creation of a replacement enterocystoplasty. In these cases, ureterocolonic or ureterorectal diversion constitutes an alternative to cutaneous diversion if its classical complications could be minimized. A ureterorectal diversion technique with rectal enlargement was performed in 6 patients: a segment of small intestine was raised, opened along its antimesenteric border, folded into a U shape and sutured to the edges of a large rectotomy. The ureters were implanted into this patch of small intestine according to the mucosal tunnel technique. This technique was used in 4 men after total cystectomy with invasion of the prostatic urethra by their bladder tumour and in 2 women for incontinence due to sphincter destruction who refused cutaneous diversion. There was no mortality in this series. The postoperative complications consisted one prolonged but resolving fever in 2 cases. Out of 12 ureteric units, 4 cases of severe stenosis had to be reoperated and 3 cases of moderate stenosis were observed. All patients were continent during the day except for one women who complained of incontinence when changing positions. All patients were continent at night and had to get up to urinate twice. This preliminary experience shows that rectal enlargement as part of a ureterorectal diversion is followed by very satisfactory functional results. The creation of a colorectal invagination valve to prevent metabolic disturbances does not appear to be necessary. The ureteric implantation technique in the mucosal tunnel should be abandoned in favour of a procedure using an ileal tube interposed between the ureters and the rectum. PMID- 1302116 TI - [Perineal gangrene. Analysis of 24 cases]. AB - Fournier's syndrome, characterised by anaerobic necrotising cellulitis of the soft tissues situated below the diaphragm, is a serous disease with an unpredictable course. From 1978 to 1991, we treated 24 men with a mean age of 57 years (27 to 90 years). Following the diagnosis of this disease, rigorous treatment was instituted immediately, consisting of a triple antibiotic combination, repeated surgical exposure, debridement and drainage with a frequent, almost systematic indication for faecal diversion (n = 16), hyperbaric oxygen therapy and classical intensive care measures. The mean interval between the first clinical signs and the diagnosis was 7.4 days. The lesions were limited to the perineum in 11 cases and extended to the abdomen, thighs and/or loins in 13 cases. The microorganisms responsible for the infection were identified in 19 cases and blood cultures were positive in 5 cases. This infection was of coloproctological origin in 12 cases, urogenital origin in 4 cases and postoperative in 2 cases, while no aetiology could be identified in 6 patients. There were 6 deaths and 18 cures without sequelae. 1. The prognosis of this disease is better in younger subjects (under the age of 60 years) with a localised clinical form, with no deterioration in the general status, sterile blood cultures and treated by a diversion colostomy. 2. A detailed aetiological work-up must be performed, looking for local or regional infection, cancer, haematological malignancy or arterial disease. PMID- 1302117 TI - [Extraperitoneal endoscopic lymph node dissection with insufflation in the staging of bladder and prostate cancer]. AB - Endoscopic pelvic lymph node dissection was performed in 30 patients as part of the staging of prostate (19) or bladder (11) cancers. The technique, using a procedure of detachment of the retroperitoneal space with CO2 insufflation, is described. Complete bilateral dissection of the ilio-obturator lymph nodes was performed in 24 patients (80%) using conventional laparoscopic surgical equipment. Only a unilateral dissection could be performed in 6 other patients because of technical difficulties. The mean operating time was 72 minutes. The intraoperative and postoperative complications consisted of 2 venous injuries and one infection. A prospective study of systemic diffusion of CO2 demonstrated that the blood Co2 level increased significantly during the procedure, but could be controlled by adaptation of the ventilation. Postoperative monitoring of blood CO2 levels using a capnograph is recommended. 4 out of 30 patients (13%), 2 with prostate cancer and 2 with bladder cancer, had lymph node metastases. Amongst the other 26 patients, 12 were treated by radiotherapy (bladder cancer), 12 patients underwent perineal prostatectomy and 12 others underwent retropubic prostatectomy (5) or prostatocystectomy (7]). No intraoperative and postoperative morbidity related to endoscopic lymph node dissection was observed in the patients subsequently undergoing a radical operation. Endoscopic retroperitoneal lymph node dissection with CO2 insufflation is a rapid, safe and effective technique for staging of malignant pelvic tumours and constitutes an alternative to open surgery and to endoscopic transperitoneal surgery. PMID- 1302118 TI - [Posterior urethral valves in newborns and infants. Treatment and clinical course]. AB - Severe forms of posterior urethral valve are essentially seen in neonates and infants. In 6 neonates under the age of 3 months, the predominant presenting features were a deterioration in the general status and renal failure. Transurethral section of the valves, after urinary drainage for an average of one month, restored patency of the lower urinary tract in every case. All children have persistent renal failure, which is moderate or severe in 4 cases. In 6 infants between the ages of 3 and 11 months, the clinical presentation was dominated by signs of infection. Section of the valve was able to be performed earlier, with subsequent urethral stricture in one case. Five infants, initially presenting with renal failure, have persistent moderate renal failure. The degree of obstruction accounts for the severity of the uropathy and its early clinical presentation. The renal prognosis is poor and related to the uretero-renal consequences of the valve as well as associated renal dysplasia. PMID- 1302119 TI - [Primary bladder lymphoma in kidney transplant recipients: report of a case]. AB - The authors report the case of a type B EBC (+) primary lymphoma of the bladder occurring in a renal transplant patient 14 months after the graft. The postoperative course had been marked by three episodes of early rejection, the last of which required the use of anti-CD3 antibody, then the later addition of cyclosporin. After immune labelling showing oligoclonal proliferation, the lesion was treated with CD24 and CD21 monoclonal antibodies. Ten months after treatment, the patient is in remission with renal function at 200 mumol plasma creatinine. Azathioprine and cyclosporin have been stopped. This apparently unique case provides the authors with an opportunity to review the usual characteristics of lymphocyte tumours in transplant patients and to stress the rarity of primary lesions of the urinary tract. They conclude that the new therapeutic approach based upon monoclonal antibodies is of value in comparison with the attempts at surgery, radiotherapy and/or chemotherapy used in the past. PMID- 1302120 TI - [Rhabdomyosarcoma of the prostate. Diagnostic course and current therapy. Report of a case of a 17-year-old boy]. AB - The authors report a case of rhabdomyosarcoma in a 17 year old boy which recurred after combination chemotherapy and radical prostatectomy, followed by death of the patient due to haematological complications of second-line chemotherapy. The diagnosis of these rhabdomyosarcomas is facilitated by the various immunohistochemical stains now available. Chemotherapy is undeniably effective and, combined with surgery and radiotherapy, ensures a 5-year survival of 47% to 93% depending on the stage. The first-line chemotherapy avoids the need for radiotherapy in the early stages and allows less mutilating surgical procedures, while maintaining the survival rate. PMID- 1302121 TI - [An exceptional complication of bladder cancer: intestinal metastases with obstruction of the small intestine]. AB - Intestinal metastases from bladder cancers are extremely rare and all of the cases reported in the international literature have concerned patients in whom the tumour was resected by open surgery. The authors report a unique case of obstructive intestinal metastases from a bladder cancer resected via the transurethral route and regularly followed by endoscopy and systematic biopsies. PMID- 1302122 TI - [New uretero-cystoneostomy in cystocecoplasties. Technique and results]. AB - Ureteric reimplantations into an intestinal segment are frequently followed by early, secondary or late stenoses. In UCN, it is essential to perform atraumatic ureteric dissection followed by reimplantation of a short ureter well vascularized by a single superior pedicle, i.e. the simplest UCN, putting the least strain on the ureter both during creation of the diversion and during subsequent healing. The ileal segment of an ileocaecocystoplasty must extend above the right iliac vessels. It is open on the antimesenteric border and its distal border is stripped of a 3 mm band of mucosa. To reach its homologue, the left ureter passes underneath the common root of the sigmoid mesocolon. Each optimally shortened ureter is placed in and fixed to the start and the end of a longitudinal mucosal tunnel, about 3 cm long. The ileum is sutured as a cuff around the orifice of each ureter. A ureteric stent is left in place for a fortnight. The ileum is sutured to the right laterocaval retroperitoneal tissue. This UCN is simple and rapid to perform. PMID- 1302123 TI - [Vesico-sphincteric disorders in patients with Parkinson's disease]. AB - Vesicosphincteric disorders are frequent in patients with Parkinson's disease, due to a lesion of the locus niger of the extrapyramidal tract which no longer secretes sufficient dopamine to activate the nigrostriatal tract. The commonest symptoms are urgent micturition, dysuria or a combination of the two. 50% of patients with Parkinson's disease present with disturbances of micturition and these symptoms may be presenting complaint of the disease in 10% of cases. Cystomanometry reveals detrusor hyperactivity in more than 60% of cases and hypoactivity in less than 30% of case, while dyssynergia is less common. Delayed relaxation of the striated sphincter may sometimes be observed. Urological problems must therefore be distinguished from urological problems in these patients. A combined urological and urodynamic assessment is essential as the risk of incontinence following prostate surgery is 20%. Stress urinary incontinence in women may mask or be associated with urgency. These vesicosphincteric disorders must therefore be treated cautiously with a combination of medical treatment (dopatherapy increases detrusor control), retraining and occasionally surgery after a detailed urodynamic assessment. PMID- 1302124 TI - [Corynebacteria D2 and encrusted cystitis with alkaline urine]. AB - In the light of an informative clinical case report, the authors emphasise the pathogenic role of Corynebacteria D2 in urinary tract disease. This microorganism can be easily detected by bacteriologists by the use of special media and such infection is suggested clinically by urinary tract infection with "sterile", strongly alkaline urine. The clinical features of incrusted cystitis with alkaline urine may be accompanied by serious upper urinary tract complications with renal failure, recurrent haematuria with anaemia, decreased bladder capacity and incontinence. Corynebacteria D2, an opportunistic pathogenic bacteria, responsible for nosocomial infection, is resistant to the majority of antibiotics. The authors complete their case report with a review of the literature. PMID- 1302125 TI - [Leiomyosarcoma of the inferior vena cava]. AB - The authors report a case of leiomyosarcoma of the infrarenal inferior vena cava presenting as an abdominal mass. CT and MR imaging and immunotyping led to the diagnosis of retroperitoneal leiomyosarcoma whose origin in the inferior vena cava was only confirmed by histological examination of the resection specimen. Surgical resection was followed by radiotherapy (4,500 rads) with a favourable course after 12 months. The progress in medical imaging and histology has considerably simplified the diagnosis of these rare retroperitoneal tumours. In the absence of any truly effective adjuvant therapy, treatment essentially consists of surgery and the clinical course is characterised by a high incidence of local recurrences. PMID- 1302126 TI - [Epididymitis disclosing an idiopathic urethroseminal reflux in children]. AB - Idiopathic urethroseminal reflux is exceptional in children. In both of our cases, it presented in the form of epididymitis and was confirmed by suprapubic cystography, which also eliminated an obstructive cause and any associated malformations. Long-term antiseptic treatment prevented recurrent infections. PMID- 1302127 TI - [Penile endoscopy: technique, results]. AB - The authors report their experience based on 200 consecutive examinations. Peniscopy is an outpatient examination of the penis using a magnification system: commercial magnifying glass or colposcope. It consists of examining the whole penis in detail with the naked eue and then with a magnitification system after application of 5% acetic acid to the glans and prepuce in order to identify subclinical lesions. Biopsies can be performed when necessary. Three basic types of lesions may be observed: concylomas, macules, papules. However, the signs of mucocutaneous lesions are difficult to interpret, especially when they are subclinical. There are 2 types of false lesions: physiological papules of the corona of the glans and a diffuse acidophilic reaction. Topical treatment or laser destruction of the lesions can be performed at the same time as the examination, when necessary. The current indications for this technique are discussed. When learning this technique, the authors recommend the extensive use of biopsies and training with an experienced examiner. PMID- 1302128 TI - [Role of pathologic anatomy in the diagnosis, prognostic evaluation, and surveillance of bladder tumors]. AB - The usual histological techniques are necessary and sufficient for the routine diagnosis of bladder tumours. Many laboratory tools are designed to determine prognostic factors but require such technical conditions that they cannot be used routinely. The determination of DNA ploidy by flow cytometry of voided urine, fresh, formalin-fixed or paraffin-embedded tumour fragments is a simple, standardised and reproducible technique and the method of choice of pathologists as it allows morphological control of the element analysed. Based on a series of 720 bladder tumours collected by 3 different centres, the authors demonstrate how to use, correlate and integrate into routine practice the data of image analysis flow cytometry in relation to conventional cytology and histology. 5% of grade 1 tumours, 27% of grade 2 tumours, and 92% of grade 3 tumours were DNA aneuploid. 17% of non-invasive tumours (PTa) and 79% of invasive tumours (PT1 and more) were DNA aneuploid. These proportions are in line with the results of various series in the literature. DNA ploidy is therefore an objective and measurable element completing histological grading. The determination of DNA ploidy also helps the cytologist in difficult cases of urine cytology. PMID- 1302129 TI - [Sub-venous iliac lymphatic dissection with celioscopy for the staging of prostatic cancer (16 patients)]. AB - Subvenous external iliac lymph node dissection is an essential element for the staging of prostatic cancer. 7 to 30% of patients with intracapsular prostatic cancer have lymph node metastases despite normal imaging examinations. Laparoscopic surgery allows lymph node dissection through a limited incision. Sixteen patients underwent laparoscopic lymph node dissection (LLND) for prostatic cancer. The mean duration of the operation was 100 +/- 50 minutes (35 180 min: 130 minutes for the first nine operations, then 60 minutes for the last seven operations). One patient died on the second day from a cerebral vascular accident. There was one technical failure (pneumoperitoneum leak), one vascular injury, one ureteric injury, one transient paresis of the obturator nerves and one case of perineal lymphoedema. The mean number of lymph nodes removed in bilateral lymph node dissection was 7.5 +/- 2 (14-20) per patient. Three patients had lymph node metastases. The mean hospital stay related to laparoscopy was 4 +/ 2 days with a median of 2 days. Laparoscopic surgery, like any conventional or innovative surgical technique, requires specific training to become safe and effective. It allows complete histological examination of the lymph nodes removed and planning of prostatectomy, which may be subsequently performed through a perineal approach. PMID- 1302130 TI - [Vesico-ureteral reimplantation on psoas bladder in lesions of the pelvic ureter. Review of 50 patients]. AB - Between 1979 and 1991, the authors performed 50 psoas bladder ureterovesical reimplantations for lesions of the pelvic ureter. 90% of very good results were obtained with this technique at the cost of a low morbidity. This series confirms the influence of previous pelvic radiotherapy on the postoperative complication rate. On the basis of the excellent results in this series, confirmed by those reported in the literature, this technique can be proposed as treatment of choice for lesions of the pelvic ureter when suture-resection or simple reimplantation cannot be performed after failure of endoluminal dilatation in patients with a life expectancy greater than 6 months to one year. PMID- 1302131 TI - [Rehabilitation of patients after cystectomy and construction of a continent intestinal reservoir]. AB - Close follow-up and rehabilitation are necessary in order to ensure a good life quality for patients who have undergone cystectomy operations combined with continent reservoir operations. A questionnaire survey was carried out on 19 of our patients with continent reservoirs of different types. Furthermore a number of the leading clinics and urologists were consulted in an effort to find out a common and reliable method for rehabilitation. The most frequently encountered problems were the sexual (13 cases: 72.2%) and psychosocial adaptation (11 cases: 61.1%) among our patients. These figures were lowered to 50% (9 cases) and 33.3% (6 cases) respectively after organizing a special club for these patients in our hospital. PMID- 1302132 TI - [Long-term prognosis of kidney cancer with vena cava thrombus. Report of 30 cases]. AB - The authors present a retrospective analysis of 30 cases of renal cancer with vena cava thrombus with a sufficient follow-up to allow analysis of the long-term prognosis. Only three patients are still alive with a follow-up of 12, 34 and 57 months. The actuarial survival for the overall population was 55%, 37% and 22% at 1, 2 and 3 years respectively. Three essential factors influenced the prognosis of these patients: the presence of distant metastases, lymph node invasion and the highest cephalic level of extension of the thrombus. Renal cancer with vena cava thrombus without metastases and without lymph node involvement has a good prognosis (100% 2-year survival), but is very rare (4 out of 30 cases), so that renal cancer with vena cava thrombus must be considered to be a serious disease (3 survivors out of 30). PMID- 1302133 TI - Acute pain management in adults: operative procedures. Agency for Health Care Policy and Research. PMID- 1302134 TI - Acute pain management in infants, children, and adolescents: operative and medical procedures. Agency for Health Care Policy and Research. PMID- 1302135 TI - Urinary incontinence in adults. Agency for Health Care Policy and Research. PMID- 1302136 TI - Pressure ulcers in adults: prediction and prevention. Agency for Health Care Policy and Research. PMID- 1302137 TI - [POEMS syndrome and papilledema]. AB - The Crow-Fukase syndrome or POEMS syndrome (Polyneuropathy, Organomegaly, Edema, Monoclonal protein, Skin changes) is an uncommon plasma cell dyscrasia leading to a multisystemic disorder. An optic disc swelling is often related to this syndrome. We report the case of a 51-year-old man with a papilledema. We presume that vasculitis or plasma cell infiltration is the cause of the papilledema. PMID- 1302138 TI - Are bifocal intraocular posterior chamber lenses superior to monofocals? AB - Twenty-eight eyes of 26 patients underwent a phacoemulsification with implantation of a bifocal posterior chamber lens (Storz-True Vista). The mean visual acuity increased from 0.28 to 0.74. To obtain best visual acuity for near, 19 eyes needed additional reading addition. A subgroup of 14 patients underwent also a phacoemulsification with implantation of a monofocal posterior chamber lens into the other eye. The mean visual acuity increased from 0.25 to 0.84. All monofocal eyes obtained an optimal near vision with a reading addition of 3 diopters. In this subgroup 9 patients preferred their monofocal eye for distance vision and 10 for near vision. Not a single patient preferred the bifocal eye. PMID- 1302139 TI - [The eye and acromegaly: apropos of a case of ptosis]. AB - A 60-year-old woman presents with bilateral ptosis and tearing, predominant on the right and existing since many years. Upper tarsus is much enlarged on the right; lacrymal glands are palpable under the upper lid and seem enlarged as well. CT scan and RMN confirms the hypertrophy of subcutaneous lid tissues, lacrymal glands and ocular muscles. The patient is aware of a progressive change in her physical aspect since years. Medical work-up diagnoses major acromegaly. Discussion about the consequences of acromegaly upon the ocular adnexa. PMID- 1302140 TI - Acanthamoeba keratitis. AB - During the last year we came across three cases of Acanthamoeba keratitis. They were all contact lens wearers. The diagnosis of Acanthamoeba keratitis was established by the history, clinical picture and the culture of corneal and conjunctival swabs. The patients were treated with metronidazole (Flagyl) 0.5% eyedrops, propamidine isethionate (Brolene) 0.1% eyedrops, Neomycin eyedrops, topical corticosteroids, mydriatics and beta-blockers. One tablet or itraconazole (Sporanox) a day was given orally. Infection subsided in two patients. The third patient still suffers from recurrent corneal erosions and shows a pronounced corneal immune reaction. PMID- 1302141 TI - Ocular manifestations of Alport's syndrome: a case report. AB - A review is given of the ocular signs characteristic for Alport's syndrome. The corneal, lenticular and fundus lesions are described. They occur in 15% of the cases. The patient reported here, showed the typical macular spots. PMID- 1302142 TI - The Walker-Warburg syndrome. AB - The Walker-Warburg syndrome is characterized by lissencephaly type II, cerebellar and retinal anomalies and congenital muscular dystrophy. A clinical and histopathological study of a case is presented and the differential diagnosis discussed. PMID- 1302143 TI - Leber's hereditary optic neuropathy: clinical and molecular genetic aspects. Preliminary results in our families. AB - Leber's hereditary optic neuropathy (LHON) is a genetic maternally transmitted disorder characterised by sudden bilateral loss of vision. The discovery of at least one mitochondrial DNA mutation associated with the disease has provided the basis for a molecular diagnosis in about 50% of families with LHON. We present a brief review of the clinical and molecular genetic aspects of LHON along with our results in 13 patients. PMID- 1302144 TI - Endogenous pneumococcal endophthalmitis after splenectomy: report of two cases. AB - Two cases of pneumococcal sepsis, meningitis and unilateral endophthalmitis after total splenectomy are described. The first patient, a 9-year-old girl, had severe panuveitis complicated by traction retinal detachment, eventually requiring vitrectomy. Due to large chorioretinal scars the visual recovery was poor. Minor residual neurological signs remained. The second patient, a 39-year-old man, showed endophthalmitis of the right eye. The recovery of the pneumococcal meningitis was complicated by severe neurological impairment. The right eye progressed to phthisis bulbi. The importance of early recognition of postsplenectomy sepsis (PSS) is emphasised since the survival rate is poor and the risk of visual loss high. PMID- 1302145 TI - A. carotis thrombosis with ocular ischemic syndrome: acute glaucoma postendarterectomy: a case report. AB - A patient develops neovascular glaucoma a few weeks after endarterectomy for carotid artery occlusion. The ocular tension is normalised after retinal photocoagulation, followed by trabeculectomy. PMID- 1302146 TI - Hyaluronidase induced orbital pseudotumor as complication of retrobulbar anesthesia. AB - The authors describe 5 patients who developed an orbital pseudotumor as a complication of retrobulbar anesthesia. Allergy tests revealed a hypersensitivity to hyaluronidase, suggesting an immunoallergic etiology of the pseudotumor, which needed to be differentiated from other causes of proptosis after retrobulbar injection. PMID- 1302147 TI - Retinal detachment surgery following implantation of a keratoprosthesis. A case report. AB - Retinal detachment is an eye with a keratoprosthesis usually has an extreme poor prognosis. We describe the successful repair of a total retinal detachment following implantation of a new type Worst-keratoprosthesis in the only eye of a 70-year-old patient. A vitrectomy, epiretinal peeling, 180 degrees superior retinotomy, subretinal membrane peeling and an injection of perfluorooctane were performed to flatten the retina. After the endophotocoagulation a perfluorooctane silicone oil exchange was performed. An additional intervention was necessary to treat a redetachment. After 3 months follow-up the retina has remained attached and the patient regained ambulatory vision. PMID- 1302148 TI - [Sturge-Weber syndrome: apropos of an anatomo-clinical case report with prepapillary glial proliferation]. AB - The authors report the case of a woman with Sturge-Weber syndrome (oculotrigeminate form) presenting with neovascular glaucoma of abrupt onset during pregnancy. Since medical treatment failed, she underwent a retrobulbar alcoholisation. Three months after delivery, enucleation was performed for esthetic reasons. The enucleated eye showed diffuse choroidal angioma, total retinal detachment and a prepapillary glial proliferation. We discuss this uncommon association. PMID- 1302149 TI - Foveomacular retinitis as a result of ocular contusion. AB - Foveomacular retinitis is typically associated with eclipse burns. However a macular hole similar to that seen in cases of solar retinopathy, may be observed after ocular contusion or after whiplash injury. The case histories of 3 men, who sustained an ocular contusion and subsequently developed as aspect typical for foveomacular retinopathy, are described. PMID- 1302150 TI - [Anatomical modification of the levator muscle of the eyelid in congenital ptosis]. AB - Congenital ptosis of the upper lid is classified as a developmental anomaly of the levator muscle. We report the histochemical findings in 38 specimens of levator muscle removed in patients with congenital ptosis and operated on by a resection of the levator muscle. Results demonstrated a close relationship between the presence or the absence of muscular fibres in the specimen and the degree of ptosis and the levator function. We suggest that congenital ptosis may result from a failure of differentiation and/or fusion of the anterior portion of the superior orbital mesoderm complex. PMID- 1302151 TI - [Adherence syndrome of the lateral recti and inferior oblique muscles]. AB - Case report of a 28-year-old woman presenting with a right abduction paresis. She also has right esotropia which was operated 14 years ago. Forced duction test was positive and there was a widening of the right palpebral fissure on attempted abduction. During reoperation we found thick adhesions between inferior oblique and lateral rectus. Freeing these adhesions restored the abduction and a normal palpebral aperture on abduction. PMID- 1302152 TI - [Photographic screening for amblyopia, strabismus and refraction errors]. AB - The authors present a photographical method to screen infants on the presence of refractive errors and squint. The photoscreener indicates an absence of focusing in one or both eyes and/or a squint. This method can be used in mass-screening of siblings, the evaluation of glasses, the monitoring of the effects of occlusion and the postoperative follow-up of patients. PMID- 1302153 TI - [Screening and treatment of fixation dominance in primary microstrabismus]. AB - The Gracis biprism appears to be the best actual method of testing eye fixation as early as 6 months. It is the appropriate test for microstrabismus screening. The treatment of the late onset microstrabismus is more simple than the treatment of the early onset microstrabismus, where the dominance of fixation is stronger. If the calibrated filters are sufficient in the first case, the optical penalisation (+ 2 D to + 3 D) on the dominant eye is the best long-term treatment in primary microstrabismus. Based on the specific aspects of the early onset strabismus, such as bi-ocularity and latent nystagmus, optical penalization without atropine offers an alternative long-term method to occlusion without any trouble of visual development of the fixating eye. PMID- 1302154 TI - [Orthoptic indications for radial keratotomy: esophoric myopia]. AB - In addition to aniseikonia, binocular factors are to be taken into consideration for refractive surgery. If important exophoria can be a contraindication to refractive surgery, this surgery can be indicated in cases of marked esophoria at near and distance vision. It can then prevent the need for prismatic treatments which become necessary in these cases. PMID- 1302155 TI - [Spiral implants in phacoemulsification and in secondary implants]. AB - The spiral I.O.L. with a rectangular optic (6 mm x 4.8 mm) is particularly convenient for small incision surgery. A series of rhexis and a series of envelope technique were compared: centering was definitely better after rhexis. In secondary implantation after ICCE the spiral implant could be secured to the posterior face of the iris. PMID- 1302156 TI - [Characteristics and prognosis of retinal detachment following uncomplicated extracapsular extraction of the crystalline lens]. AB - In a retrospective study dealing with 52 eyes, we compare the features and prognosis of retinal detachment following intracapsular cataract extraction, non complicated extracapsular cataract extraction, extracapsular cataract extraction followed by YAG laser posterior capsulotomy, extracapsular cataract extraction complicated by peroperative rupture of the posterior capsule with phakic retinal detachment. Our results show several common features between retinal detachment after non complicated cataract extraction and phakic retinal detachment. Cataract extraction, no matter the technique, is not per se an anatomic or functional prognosis factor for a subsequent retinal detachment. PMID- 1302157 TI - [Treatment of choroidal nevi and melanomas using cryo-applications: preliminary study]. AB - Since 1989 we use cryocoagulations (alone or in association with Argon laser coagulations) to treat selected cases of evolutive choroidal naevi or melanomas located near the posterior pole of the eye. We report our results in 9 consecutively treated patients. PMID- 1302158 TI - Radiation-induced optic neuropathy. AB - Radiation-induced optic neuropathy is a well-known complication of cranial radiotherapy. We describe four cases. In two cases, the diagnosis was made on MRI. After administration of Gadolinium-DTPA, there was an enhanced captation at the level of the optic nerve. In addition we reviewed 47 cases reported in the literature. Visual prognosis is less than 1/10 in 78% of affected eyes. In case of associated brain necrosis, the mortality rate is 62%. PMID- 1302159 TI - Vascular renin and regulation of blood pressure. PMID- 1302160 TI - The French multicentre study of ramipril in ambulatory patients with mild-to moderate hypertension. AB - The aim of this 16-week trial was to determine the safety and efficacy of a step care regimen of ramipril, an angiotensin converting enzyme inhibitor, from the minimal active dose (2.5 mg) in patients treated for mild to moderate hypertension. The trial was conducted by 102 general practitioners in 770 patients with mild to moderate hypertension. After a response rate to a 4-week placebo therapy of 9.1%, 57.0% of patients given active treatment with ramipril responded to daily doses of 2.5 mg. Ramipril 5 mg daily was effective in 55.6% of the remaining patients. There was no apparent statistically significant difference between the treatments with ramipril 10 mg or a combination of ramipril 5 mg + Lasix 20 mg daily (44.7% and 47.4% response respectively) in a 6 week double-blind arm of the study. In total, more than 90% of patients responded to treatment with ramipril by the end of the study. The incidence of adverse events was generally low, such as headache, cough, dizziness, asthenia, cramps and nausea. The incidence of cough appeared to be related both to the dosage of ramipril given and to outbreaks of influenza syndrome. Thirty-eight patients discontinued active treatment as a result of minor events such as cough, dizziness or diarrhoea, and one case each of myalgia and papular rash. There were no significant variations in laboratory parameters during the study, especially fasting blood glucose and apolipoprotein A1 and B. The results of this study provide evidence of the safety and efficacy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302161 TI - Influence of ramipril on plasma atrial natriuretic peptide, antidiuretic hormone, angiotensin II and aldosterone in patients with chronic congestive heart failure. AB - In an open trial 5 mg ramipril daily for 2 weeks was administered to 11 patients with congestive heart failure. 24-hour plasma profiles of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), angiotensin II (Ang II) and aldosterone (Aldo) were determined before and on days 1 and 15 of ramipril treatment, respectively. Urinary sodium excretion was also measured at the same time points. There were no relevant differences in the 24-hour profiles of ANP and ADH. Ang II values dropped as expected on the first day of ramipril treatment from 11.2 pg/ml to 2.9 pg/ml at 3 h post administration and from 6.7 pg/ml (predose) to 1.8 pg/ml at 2 h post administration on day 15. Plasma aldosterone values increased slightly from day 1 to day 15, sodium excretion increased from 125.9 mmol to 166.5 mmol/24 h; however, both changes in the 24-hour profiles were nonsignificant. A clinically relevant improvement in the severity of CHF was observed. From a total of 121 reported symptoms according to McKee et al., 35 showed an improvement; 81 remained unchanged, in only 5 symptoms a deterioration was observed. According to the NYHA-classification 5 patients improved from grade III to II, 6 remained unchanged. CONCLUSION: ACE inhibition does not induce changes in ANP or ADH levels in the resting state while Ang II decreases. A slight increase in aldosterone levels may be due to increased sodium excretion. PMID- 1302162 TI - Tissue ACE inhibition and organ protection. PMID- 1302163 TI - ACE inhibition and renal protection. AB - In patients with renal disease, altered renal function causes elevation of blood pressure, but hypertension in its turn accelerates progression of renal failure. Lowering of blood pressure into the normotensive range is beneficial for slowing progression. Increasing incidence suggests that in this respect ACE inhibitors have unique benefits (renoprotective action). PMID- 1302164 TI - Cardioprotection and ACE inhibitors. AB - Angiotensin converting enzyme inhibitors are now widely used in the treatment of hypertension and heart failure. They are clearly as effective as other conventional antihypertensive agents in reducing blood pressure and combined with diuretics seem likely to transform current management of chronic heart failure. Myocardial infarction remains the major cause of death in patients with raised blood pressure and current studies should establish whether the attractive features of ACE inhibitors translate into reduction in the rate of infarction or its consequences. Similarly, whilst symptomatic benefit undoubtedly accrues from their use in heart failure it is less clear that they can prolong life particularly when used in the immediate setting of a myocardial infarction. Again a number of ongoing major trials are set to establish whether these drugs reduce death in patients with chronic heart failure (V-HeFT II, SOLVD) and in patients immediately after myocardial infarction (CONSENSUS II, SAVE,. AIRE, GISSI III and ISIS IV). The physician has a wide choice of ACE inhibitors with different pharmacological profiles for clinical use. PMID- 1302165 TI - Acute effects of experimental diabetes on skeletal muscle contractile functions. AB - The study was planned to explore the short term effects of experimental diabetes on the contractile characteristics of soleus and diaphragm. Experimental diabetes was induced in rats by streptozotocin (50 mg/kg, IP). On the 5th day, the isometric contractions were studied in soleus (in situ) and in diaphragm strip (in vitro). The soleus of the diabetic group showed similar twitch characteristics and tetanic tensions, decreased maximal relaxation rate (MRR; p < 0.01) and increased endurance time (ET; p < 0.05) as compared to the control group. The diaphragm of the diabetic group showed greater twitch tension (p < 0.05) and tetanic tension (p < 0.01), increased MRR (p < 0.02) and similar ET compared to the control group. It is concluded that the streptozotocin-induced diabetic state produces differential effects on the skeletal muscle contractile characteristics. PMID- 1302166 TI - Postoperative hyperfibrinogenemia in gastrointestinal surgery. AB - Fibrinogen titres were determined in two groups of patients undergoing major abdominal and thoracic surgical operations. Patients who underwent gastrointestinal surgical procedures had higher fibrinogen levels than those subjected to other appropriate thoracic surgical procedures. Fibrinogen titre elevation in patients with gastrointestinal abnormalities were significant on the 3rd, 5th and 7th days after surgery compared with the other group of patients. This higher response in fibrinogen could be attributable to the greater smooth muscle content in the gastrointestinal system than in the other tissues considered in this study. Smooth muscle tissue inflammation may lead to acute circulatory problems through postoperative increase in fibrinogen concentration. PMID- 1302167 TI - Serum sex hormone binding globulin in prepubertal girls and adult women. AB - Serum SHBG concentration depends on the hormonal status. Androgens decrease while estrogens increase SHBG biosynthesis in the liver. In the present study an attempt was made to investigate whether the changes that occur in the ratio of estrogen to androgen concentration between prepubertal girls and women could have influenced plasma SHBG levels. For this reason serum concentrations of SHBG, E2, T and DHEA-S were measured in 31 girls, aged 4.5-9 years, at Tanner stage I of pubertal development, and in 24 normal women. The girls were divided into 2 groups of different ages. The concentrations of non-SHBG-bound E2 and T and free E2 and T were calculated. The results showed a negative correlation between SHBG serum levels and the age of prepubertal girls while the ratio of E2/T did not change. Although the ratio of E2/T was found increased by 10 times between older prepubertal girls and women in the luteal phase of menstrual cycle, serum SHBG levels only slightly decrease in the group of women. The non-SHBG-bound E2 and free E2 levels were significantly higher in women than those in prepubertal girls indicating an increase of estrogen milieu in target tissues. It seems that apart from the changes that occur in the ratio of E2/T the serum SHBG levels may be also under the control of other factors. PMID- 1302168 TI - Role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine-induced stimulation of H+ output in the rat. A new hypothesis for the mechanism of gastric acid secretion. AB - This study was undertaken in the rat to examine the role of 5-hydroxytryptamine (5-HT) in the mechanism of reserpine (0.1 mg/kg)-induced stimulation of gastric acid secretion. Reserpine significantly (p < 0.001) stimulated acid secretion relative to control values (197 +/- 3.1 vs 61 +/- 1.7 mumol, mean +/- SEM, n = 10). Atropine (5 mg/kg) and cimetidine (40 mg/kg) were equally effective in achieving a significant (p < 0.001) suppression of the reserpine-induced acid secretion (98 +/- 3.4 and 91 +/- 2.9 mumol, respectively, vs 197 +/- 3.1 mumol, mean +/- SEM, n = 10), an action intensified by administering them together, but not significantly so (84 +/- 5.3 mumol). Vagotomy was more effective (p < 0.001) than the latter combination in preventing acid stimulation by reserpine and allowed an acid output similar to that of vagotomy controls (14 +/- 1.2 vs 13 +/- 1.4 mumol, mean +/- SEM, n = 10). Dose dependent inhibition of the reserpine induced stimulation of acid secretion was achieved by the 5-HT receptor antagonist methysergide, an inhibition significantly (p < 0.001) more effective than that afforded by vagotomy coupled with achlorhydria in 80% of animals was noted with the 5-20 mg/kg doses. Reserpine produces vagal adrenergic delivery to the stomach, which releases acid secretagogues and sensitizes parietal cells to them besides stimulating acid secretion, and 5-HT is discharged into the gastric mucosa by vagal adrenergic activity and by reserpine and liberates acid secretagogues by a paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302169 TI - Iron accumulation by bovine aortic endothelial cells. AB - Bovine aortic endothelial cells in monolayers were used to study iron and transferrin binding and transport mechanisms. Diferric bovine transferrin labeled with 59Fe was used as an iron donor. We have shown the presence of saturable iron uptake when cells were incubated with varying concentrations of diferric transferrin. This uptake decreased when the cells were treated with trypsin, ammonium chloride and methylamine. The effects of the latter two could be reversed by the addition of 2.0 mM Ca2+. Energy dependence was shown by using various electron transport/oxidative phosphorylation inhibitors. The presence of transferrin receptors on the cell surface was confirmed by their isolation, SDS PAGE and autoradiography. There were approximately 1.5 x 10(6) transferrin receptors per cell with a Kd of 9.1 x 10(-7) M in the physiological iron range. Iron was also taken up when the cells were incubated with radioactive ferrous iron without transferrin. Uptake was not affected by receptor-mediated endocytosis inhibitors. Calcium increased ferrous iron uptake and overcame the effects of metabolic inhibitors on iron uptake from transferrin. A ferrireductase was detected in cell membranes. It is proposed that iron is transported by bovine endothelial cells by two mechanisms: one is receptor-mediated endocytosis from transferrin, and the other involves a non-endocytic mechanism from transferrin and Fe2+, which is possibly promoted by Ca2+. PMID- 1302170 TI - A novel study on the effect of acetylsalicylic acid on the binding capacity of estrogen receptors from MCF-7 cells. AB - The effect of acetylsalicylic acid (ASA, aspirin) was investigated on [3H] estradiol-17 beta ([3H]-E2) binding to estrogen receptors (ER) from MCF-7 mammary tumour cells. No effect was observed using the monoclonal estrogen receptor enzyme immunoassay (ER-EIA). In contrast to the ER-EIA, the radioreceptor assay (RRA) showed decreases of [3H]-E2 specific binding in the presence of increasing amounts of ASA. It is therefore concluded that these results demonstrate that ASA possibly affects the direct binding of E2 to region E of the ER of human breast cancer MCF-7 cells, but does not affect binding of monoclonal antibodies to regions D and F of the ER. PMID- 1302171 TI - Is re-communication of vagal branches responsible for the recurrence of duodenal ulceration after proximal gastric vagotomy? A study in the rat. AB - This study was carried out in the rat to examine whether preventing the re communication of vagal fibres with their distal stumps after proximal gastric vagotomy (PGV), by placing a patch against the bare area of lesser curvature, impairs the return of gastric secretory patterns to their pre-operative levels and reduces the incidence of duodenal ulceration. PGV alone or with a patch significantly depressed the basal acid output. Administration of insulin (1 unit/kg i.p.) failed to stimulate this output. Two years later, the basal acid output of PGV was significantly (p < 0.05) higher than that of PGV with a patch (7.8 +/- 0.2 vs 3.7 +/- 0.3 mumol, mean +/- SEM), but significantly (p < 0.01) lower than that of the control animals (7.8 +/- 0.2 vs 14.2 +/- 0.8 mumol, mean +/- SEM). Insulin did not stimulate the acid output of PGV with a patch, but significantly (p < 0.001) stimulated the PGV acid output (7.8 +/- 0.2 vs 28.9 +/- 0.6 mumol, mean +/- SEM). This stimulation was significantly (p < 0.001) less than that noted in the control animals. PGV alone or with a patch equally prevented acid stimulation and production of duodenal ulceration by the infusion of pentagastrin (4 micrograms/kg/min) and carbachol (0.8 microgram/kg/min) for 24 hours. Two years later, these secretagogues significantly (p < 0.001) stimulated acid secretion in the PGV group relative to control values (24.1 +/- 2.3 vs 13.9 +/- 0.5 mumol, mean +/- SEM) and produced duodenal ulceration in 19% of the animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302172 TI - Symposium on secondary metabolites: their function and evolution. London, 18-20 February 1992. Proceedings. PMID- 1302173 TI - Genes for the biosynthesis of beta-lactam compounds in microorganisms. AB - Rapid progress has recently been made in the characterization of genes and gene clusters involved in the biosynthesis of beta-lactam antibiotics such as penicillins, cephalosporins and cephamycins. The biosynthetic pathways are found in a wide range of microorganisms, including fungi, actinomycetes and Gram negative bacteria. Comparisons of gene sequences (particularly the genes encoding isopenicillin N synthetase) and gene organization in these different microorganisms have led to proposals about the evolution of this group of pathways, and how they might have been transferred from prokaryotes to eukaryotes. The isolation and characterization of the genes encoding ACV (tripeptide) synthetase, the first step in the beta-lactam biosynthetic pathway, have revealed the presence of three partly repeated domains, most likely responsible for the recognition, adenylation and activation of the three amino acid precursors of the penams and cephems. This has confirmed their classification as peptide synthetases, distantly related to enzymes responsible for the synthesis of peptide antibiotics in Bacillus brevis and other bacteria and fungi. PMID- 1302174 TI - Regulation of gibberellin formation by the fungus Gibberella fujikuroi. AB - Gibberellins are a classic example of the production of plant growth regulators by microorganisms. They are important biotechnological products and are increasingly used in agriculture and horticulture. The economic importance of these plant hormones has led to an extensive study of the regulation of gibberellin biosynthesis. There have been reports of light, growth rate, inoculum size and carbon and ammonium sources acting as regulators of gibberellic acid biosynthesis. Besides light stimulation, nitrogen repression is a well-known regulatory principle of secondary metabolite formation. In Gibberella fujikuroi ammonium interferes with the production of gibberellic acid whereas phosphate does not influence the biosynthesis. It was found that the negative effect of ammonium ions is due to both the inhibition of activity and the repression of de novo synthesis of specific gibberellin-producing enzymes. Besides nitrogen control, the biosynthesis of gibberellins is suppressed by glucose. This glucose effect can be overcome by the addition of mevalonic acid. Therefore, the key enzyme of the isoprenoid pathway, the HMG-CoA reductase, seems to be the target of C-catabolite repression. A detailed knowledge of the regulation of gibberellin biosynthesis is important for fermentation processes. The biological function of gibberellin formation for the producing fungus is discussed. PMID- 1302175 TI - Genetic regulation of secondary metabolic pathways in Streptomyces. AB - Streptomyces species are (along with the fungi) the best-known antibiotic producing organisms. Often, they make several different antibiotics. The biosynthesis of each antibiotic is encoded by a complex gene cluster that usually also contains regulatory and resistance genes. Typically, there may be more than one such pathway-specific regulatory gene per cluster. Both activator and repressor genes are known. Some of the regulatory genes for different pathways are related. In S. coelicolor, expression of several such biosynthetic gene clusters also depends on at least 11 globally acting genes, at least one of which is involved in the translation of a rare codon (UUA). A protein phosphorylation cascade also seems to be involved. Gene clusters closely similar to those for the biosynthesis of aromatic polyketide antibiotics determine spore pigment in some species. These genes show different regulation from antibiotic production genes. The evolution of gene clusters for polyketide antibiotics, and the possible adaptive benefits of secondary metabolism, are discussed. PMID- 1302176 TI - Terpenoid cyclases: design and function of electrophilic catalysts. AB - Terpenoid cyclases catalyse the cyclization of the universal acyclic precursors geranyl and farnesyl diphosphate to monoterpenes and sesquiterpenes, respectively. All such cyclases investigated to date are operationally soluble, moderately lipophilic proteins of relative molecular weight 40,000-100,000, requiring no cofactors other than a divalent metal, usually Mg2+ and occasionally Mn2+. The focus of most work has been on the mechanisms of the cyclization reactions themselves. It is currently proposed that the cyclase binds the acyclic substrate in a suitable conformation and initiates the cyclization by ionization of the labile allylic diphosphate moiety. The use of stereospecifically labelled substrates and analysis of the sites of labelling in the derived cyclization products has allowed the proposal of detailed cyclization mechanisms. Further insight into the architecture and function of the cyclase active site has come from the study of substrate and intermediate analogues designed to act as potential inhibitors or anomalous substrates of the normal cyclization reaction. Progress has also been made on the cloning of the relevant structural genes for sesquiterpene cyclases. This has led to new insights into the basic requirements for cyclase catalysis and specificity. PMID- 1302177 TI - Roles of secondary metabolites from microbes. AB - The common feature of the seemingly diverse array of biological activities exhibited by microbial secondary metabolites is their survival value for the producing organism. The propensity to form these compounds is unevenly distributed in microbial taxa and seems more closely associated with existence in a competitive environment than with phylogeny. The characteristic multibranched elaboration of secondary biosynthetic pathways and the marked species specificity of the end products are consistent with their evolution by an 'inventive' mechanism. The species specificity suggests that distinctive terminal reactions may be of recent origin. However, comparisons of the nucleotide sequence of genes involved in the biosynthesis of phenazine and polyketide metabolites with related genes of primary pathways indicate that the secondary pathways have not evolved exclusively within the organisms in which they are now found. Sequence similarities with related primary pathway genes in phylogenetically distant organisms suggest that gene transfer has played an important part in the evolution of secondary metabolism. The diversity of products may reflect the many roles for which secondary metabolites have been selected after the genes for their biosynthesis have transferred to organisms with different physiologies and different environment challenges. PMID- 1302178 TI - Self-protection mechanisms in antibiotic producers. AB - Various ways in which antibiotic-producing organisms are able to resist the actions of their products are discussed. Examples are given of antibiotic inactivation and also the modification of antibiotic target sites (most notably, ribosomes) to which drugs would otherwise bind and thereby exert their usual inhibitory effects. An interesting variation on the latter theme involves the duplication of target enzymes so that both sensitive and resistant versions are produced, the latter inducibly. Speculative discussion of antibiotic efflux leads to examples of cloned resistance determinants that probably encode components of efflux systems. Although of interest in their own right, resistance mechanisms should not be viewed narrowly when the physiology of antibiotic producers is considered. Thus, chemical modification of drug molecules may not only fulfil a protective role within the cell but may also provide substrates for efflux. Recent evidence that such considerations apply to macrolide antibiotics is presented. The control of resistance in producing organisms is also discussed with particular reference to the induction of novobiocin resistance in Streptomyces sphaeroides. This involves the interplay of novobiocin-sensitive and -resistant forms of DNA gyrase and features a promoter that displays a dramatic response to changes in DNA topology. PMID- 1302179 TI - Useful functions of microbial metabolites. AB - The mood-enhancing effects of fungi and their medicinal properties have been recognized for centuries. Ergot was initially used by midwives to speed childbirth in the Middle Ages. More recently their pharmacological action on dopamine receptors has been exploited to treat post-partum bleeding, migraine, Parkinson's disease and senile dementia. Further indications of the potential value of microbial metabolites are exemplified by the discovery and development of cyclosporin, to treat organ rejection, and mevinolin, a cholesterol-lowering drug. Such discoveries are not unexpected because we have known for some time that fungi regulate morphogenesis, differentiation and sexuality via hormonal molecules, ranging from peptides through to steroidal molecules similar in structure to human sex hormones. A combination of the power of molecular biology to design screens based on isolated disease mechanisms with the chemical inventiveness of microorganisms is providing numerous new pharmacophores for drug development. PMID- 1302180 TI - Secondary metabolites from marine organisms. AB - Marine macroorganisms and microorganisms, like terrestrial species, produce a dizzying array of secondary metabolites, including terpenes, steroids, polyketides, peptides, alkaloids and porphyrins. Most of the marine metabolites are found in terrestrial species as such or have close counterparts in land-based species, but some are sufficiently unusual to constitute a separate class (e.g. marine sterols). Although in many cases the functions of these secondary metabolites in the marine species themselves are unclear, other compounds play well-defined roles-for example as trail markers, sexual attractants, antifouling substances or antifeedants. What is clear is that many of the most interesting marine secondary metabolites have potent activities largely unrelated to their in situ roles. Examples abound of antitumour, antiviral, immunosuppressive and antimicrobial agents, as well as neurotoxins, hepatotoxins and cardiac stimulants. Relatively few biosynthetic studies of marine secondary metabolites have been done because of the logistical problems of working under water and the primitive state of techniques for growing marine invertebrates in culture. However, recent studies indicate that many compounds isolated from marine macrospecies (e.g. sponges) may instead be produced by microorganisms (e.g. bacteria or phytoplankton). Studies of these symbionts may facilitate efforts to understand the biosyntheses of these metabolites. PMID- 1302181 TI - Evolution of secondary metabolite production: potential roles for antibiotics as prebiotic effectors of catalytic RNA reactions. AB - It has been proposed that organic molecules related to known secondary metabolites have existed since the beginning of biochemical evolution and were present in primordial soups. Under primitive earth conditions certain of these molecules may have played roles as effectors in prebiotic reactions, especially those involving catalytic RNA (ribozymes). We demonstrate that a number of antibiotic-related secondary metabolites bind to group I introns and either inhibit splicing reactions or promote the formation of intron oligomers. This is consistent with the functional co-evolution of catalytic RNA and secondary metabolites as antibiotic inhibitors of translation, and supports the notion of an evolutionary relationship between group I introns and ribosomal RNA. PMID- 1302182 TI - Roles for secondary metabolites in plants. AB - More than about 20,000 secondary metabolites have now been identified and their isolation and characterization continues at an undiminishing rate. Although the production of most secondary metabolites is under genetic control, in relatively few cases have convincing arguments been put forward to rationalize their occurrence in terms of primary metabolic functions. Whatever the initial reason for their evolution, secondary metabolites are now an essential part of the armamentaria used by plants in the battle to survive and propagate, to the extent where the expenditure of energy, photosynthate and nutrients for their production can be demonstrated to be 'cost effective' for that. Their role may centre on defence of the producer against predators (herbivores), pathogens or competitors, on aid to pollination or seed dispersal, or on protection against or adaptation to extrinsic abiotic factors, or on combinations of these functions. Various examples are given in support of this argument. PMID- 1302183 TI - Defensins: endogenous antibiotic peptides from human leukocytes. AB - A variety of endogenous antimicrobial peptides equip mammals, amphibians, insects and plants to defend themselves against microbial pathogens. Defensins are small peptides of mammalian cells that contain 29-35 amino acid residues, including six invariant cysteines that form three intramolecular disulphide bonds. They are produced by the sequential proteolysis of precursors that contain approximately 95 amino acids and are synthesized by several types of cells, especially the bone marrow precursors of blood neutrophils. Defensins constitute 5-7% of the total protein in human neutrophils and are present in high concentration in the azurophil granules and phagocytic vacuoles. The production of defensins by human neutrophils amounts to approximately 10 mg/kg body weight per day. In certain mammalian species lung macrophages and specialized epithelial (Paneth) cells in the small intestine also produce defensins. Defensins are complexly folded, amphipathic, rich in antiparallel beta-sheet but devoid of alpha-helical domains. Their unusually broad antimicrobial spectrum encompasses Gram-positive and Gram negative bacteria, many fungi, mycobacteria, spirochetes and several enveloped viruses. The antimicrobial properties of defensins result from their insertion into target cell membranes and the formation of voltage-sensitive channels. Given their abundance and broad spectrum of antimicrobial activity, defensins may contribute substantially to innate resistance to infection. PMID- 1302184 TI - Microbial secondary metabolism: a new theoretical frontier for academia, a new opportunity for industry. AB - Microbial secondary metabolites are the low molecular mass products of secondary metabolism. They include antibiotics, pigments, toxins, effectors of ecological competition and symbiosis, pheromones, enzyme inhibitors, immunomodulating agents, receptor antagonists and agonists, pesticides, antitumour agents and growth promoters of animals and plants. They have a major effect on the health, nutrition and economics of our society. They have unusual structures and their formation is regulated by nutrients, growth rate, feedback control, enzyme inactivation and induction. Regulation is influenced by unique low molecular mass compounds, transfer RNA, sigma factors and gene products formed during post exponential development. The synthases of secondary metabolism are often coded by clustered genes on chromosomal DNA and infrequently on plasmid DNA. The pathways of secondary metabolism are still not understood to a great degree and thus provide a new frontier for basic investigations of enzymology, control and differentiation. Cloning and expression of genes in industrial microorganisms offer new opportunities for strain improvement and discovery. Microbial metabolites have already established themselves as coccidiostats, immunosuppressants, antihelminthic agents, herbicides and cholesterol-reducing drugs. Great potential exists for the discovery of antiviral, antiparasitic, antitumour and pharmacological compounds and new agricultural products. The future for natural products is bright indeed. PMID- 1302185 TI - Why are secondary metabolites biosynthesized? Sophistication in the inhibition of cell wall biosynthesis by vancomycin group antibiotics. AB - The evidence that secondary metabolites serve sophisticated roles in the survival strategy of the producer is briefly reviewed. This evidence stems from the common involvement of tens of kilobases of DNA in the programming of their synthesis, of up to several tens of discrete enzymic conversions in their biosynthesis, and of the existence of sophisticated mechanisms in the producers for resistance against their physiological effects. It also stems from a study of the molecular basis for these physiological effects. The molecular basis for the antibacterial action of the vancomycin group antibiotics is presented, and demonstrates that essentially every portion of these molecules appears to be finely honed to promote efficient antibacterial action. PMID- 1302186 TI - Origins of secondary metabolism. AB - Secondary metabolites generally benefit their producers as poisons that protect them against competitors, predators or parasites. They are produced from universally present precursors (most often acetyl-CoA, amino acids or shikimate) by specific enzymes that probably arose by the duplication and divergence of genes originally coding for primary metabolism. Most secondary metabolites are restricted to single major taxa on the universal phylogenetic tree and so probably originated only once. But different secondary metabolic pathways have originated from different ancestral enzymes at radically different times in evolution. Secondary metabolites are most abundantly produced by microorganisms in crowded habitats and by plants, fungi and sessile animals like sponges, where chemical defence and attack rather than physical escape or fighting are at a premium. The first secondary metabolites were probably antibiotics produced in microbial mats over 3500 million years ago. These first ecosystems probably consisted entirely of eubacteria: archaebacteria and eukaryotes arose much later. As a phylogenetic context for considering the earliest origins of antibiotics I summarize a cladistic analysis of the explosive eubacterial primary diversification. This suggests that the most primitive surviving cells are the photosynthetic heliobacteria. Study of these and of the nearly as primitive chloroflexibacteria, spirochaetes and deinobacteria may provide the best evidence on the origins of secondary and primary metabolism. PMID- 1302187 TI - Genes for polyketide secondary metabolic pathways in microorganisms and plants. AB - Recent advances in molecular genetics have led to the isolation, sequencing and functional analysis of genes encoding synthases that catalyse the formation of several classes of polyketides. The structures of the genes and their protein products differ strikingly in the various examples. For Streptomyces aromatic polyketides, exemplified by granaticin and tetracenomycin, the synthases correspond to Type II (bacterial and plant) fatty acid synthases in consisting of distinct proteins for such processes as condensation, acyl carrier function and ketoreduction. In contrast, for actinomycete macrolides such as erythromycin, similar catalytic functions are performed by a set of multifunctional proteins resembling Type I (animal) fatty acid synthases, but with every step in chain building being catalysed by a different enzymic domain. Penicillium patulum has a simple Type I synthase for 6-methylsalicylic acid. For plant chalcones and stilbenes, a single small polypeptide acts as a condensing enzyme for carbon chain-building and may be unrelated to any of the other polyketide and fatty acid synthases. Thus, although these systems share a common general mechanism of chain assembly, they must differ in the ways that synthase 'programming' has evolved to determine chain length, choice of chain starter and extender units, and handling of successive keto groups during chain assembly, and so control the great diversity of possible chemical products. PMID- 1302188 TI - [Analysis of polynuclear aromatic hydrocarbons in kitchen and determination of urinary 1-hydroxypyrene of cooks]. AB - Polynuclear aromatic hydrocarbons in the air of kitchen were determined using HPLC coupled with a fluorescence detector during the period of frying and cooking. About 40% of the benzo(a)pyrene were in the air and most of the benzo(a)pyrene were gathered on the smaller particles (less than 10 microns). Urinary 1-hydroxypyrene from 21 cooks was determined, its mean value was 0.627 mumol/mol creatinine, comparing with the control mean of 0.260 mumol/mol creatinine t test, showed that difference is statistically significant. PMID- 1302189 TI - [Study on the frequency of primary rubella infection among early pregnant women]. AB - Rubella virus is the common agent of prenatal infection. Congenital malformation rate is very high among pregnant women who are infected rubella primarily during the first trimester of pregnancy. Sera were taken from 10412 early pregnant women in 4 cities and 4 countries of 6 Provinces in 4 districts of China from April 1990 to October 1991 for detection of special IgM antibodies against rubella with Capture-EIA test. The results showed that the primary infection rate was 0.318% of those women without clinical symptoms of rubella during their early pregnant period. A high infection rate of 1.477% was found in those women with clinical symptoms, 4.7 times the former rate. The total infection rate of 10,412 women was 0.461%. By this rate at least some 40 thousand CRS infants will be born each year in China. This figure is more than the sum of patients suffering from poliomyelitis and Japanese encephalitis, and much more than the number disabled from these two infectious diseases. Some suggestions to prevent CRS were put forward in this paper. PMID- 1302190 TI - [The study of biological monitoring index for human exposed to BaP]. AB - This paper studied the relationships among urinary BaP, Plasma BaP and SCE in rats and also analysed humans date. The results of animal experiments showed urinary BaP concentration were significantly correlated with BaP in plasma (r = 0.814, P < 0.01) and with the difference of the SCE frequency before and after BaP administration (r = 0.934, P < 0.01). The analytical results of humans data showed similar linear relationship between urinary BaP concentration and the level of exposure to BaP (r = 0.987, P < 0.0005), and also showed a positive correlation between the concentration of urinary BaP and the SCE frequency (r = 0.733, P < 0.05). We suggest the use of urinary BaP analysis as a biological monitoring index for exposure to BaP. PMID- 1302191 TI - [Stroke, coronary heart disease and all cause mortalities analyses for hypertension]. AB - The mortalities of 870 hypertensives, aged 35 and over, during 1986-1988 in a community were analysed, and SMRs (standardised mortality ratio) were calculated according to the data of population and mortality in the community. The results showed that, among the hypertensives, all cause death and stroke death were related to the level of systolic blood pressure beside the age. SMR analyses indicated that stroke death level in the group with hypertension was significantly higher than general population, and the extra death for all cause death, stroke and CHD (coronary heart disease) in the hypertensive group of less than 60 years old were particularly higher. However the SMR in the group of 70 or over were close to 100 or even lower than 100. It suggested that more consideration should be given to the hypertensives of younger age group (less than 60). PMID- 1302192 TI - [Toxicity of chongqing acid fogwater on rabbit alveolar macrophages in vitro]. AB - We collected acid fogwater on a fogday and observed its toxic effects on rabbits' pulmonary alveolar macrophages (AM) in vitro. The fogwater was diluted into 4 concentrations: 1, 1/10, 1/100, and 1/1000 of the original fogwater and the exposure time was 12 hours. The results showed that both the AM's viability and the phagocytic capacity were depressed significantly, but the AM's lysosomal enzyme--acid phosphatase activity was found to be stimulated to increase. All these changes were directly correlated with the degree of pollution of the fogwater. Of these three toxicity indices, the most sensitive one was the change of AM's phagocytic capacity. PMID- 1302193 TI - [Effects of harman and norharman on aflatoxin B1 and aminopyrine metabolism by phenobarbital and 3-methylcholanthrene-induced rat liver microsomes]. AB - Harman and norharman are two beta-carboline derivatives known to be present in certain foods and are formed during pyrolysis of amino-acids. Their effects on the metabolism of aflatoxin B1 and aminopyrine by 3-methylcholanthrene and phenobarbital-induced rat liver microsomes were studied. Both harman and norharman markedly inhibited the metabolism of aflatoxin B1 to its hydroxylated derivative, aflatoxin M1. However, only norharman showed an inhibitory effect on aminopyrine N-demethylation; harman had no effect. Harman and norharman inhibited aflatoxin B1 binding to DNA, mediated by hepatic microsomes in vitro. PMID- 1302194 TI - [Investigations on ragweed pollens in the air in Qingdao District and its allergenicity]. AB - A survey of the distribution of ragweed in Qingdao district was carried out. Ambrosia-artemisifolia has been found to be widespread in many areas. The results of the survey showed that ragweed pollen was the chief allergen of the district and that it was 18%-21.3% of total air-borne pollen in a year. Skin tests with Ambrosia allergen extracts showed a positive rate of 67.7% in 624 cases of pollinosis. Ragweed pollens have become the major allergic pollen, causing important pathogenesis with pollinosis in the district. Preventive measures must be taken to eradicate ragweed. Otherwise it certainly will spread all over China. PMID- 1302195 TI - [Study on the pathogenic factors of pneumoconiosis in Beijing coal district]. AB - Ferruginous bodies were first found in the lung tissues of coal miner autopsies in Beijing Coal mining. District irrespective of the presence or not pneumoconiosis, ferruginous bodies were found in the lung tissues as examined with two methods, tissue section and digestion and there was significance difference in their number. Two kinds of ferruginous bodies, one a "coal body", the other an "amphibole body" were distinguished when examined by EDXA. The fibrous particles in the dust extracted from the lung tissue are the physical basis of ferruginous bodies formation. After the lung dust has been subjected to X-ray diffraction analysis, there are also amphibole bodies in the lung tissue. There is no doubt that the presence of asbestos in the coal mine is one of the pathogenic factors of pneumoconiosis. PMID- 1302196 TI - [Studies on metabolism of fungicide benzoic acid, 1,3-dithiolan-2 ylidenehydrazide in vitro]. AB - The metabolism of fungicide benzoic acid, 1,3-dithiolan-2-ylidenehydrazied (Yekuling) was studied quantitatively in rat liver microsomes and liver soluble fractions pretreated with phenobarbital (PB) and 3-methylcholanthrene (3-MC) by high pressure liquid chromatography. The experimental results indicated that the major metabolic pathway of Yekuling in vitro was hydrolysis. PB can enhance amidase activity to increase formation of benzoic acid and 1,3-dithiolan-2 ylidenehydrazine. 3-MC treatment elevated rat liver microsomal cytochrome P-448, enhancing S-oxidation of Yekuling. On the other hand, S-oxidation of Yekuling by rat liver microsomal MFO was NADPH-dependent. PMID- 1302197 TI - [Protective action of seed oil of Hippophae rhamnoides L. (HR) against experimental liver injury in mice]. AB - Protection by seed oil of HR against hepatic injury induced by CCl4, ethyl alcohol and acetaminophen (AAP) on mice was studied in this paper. It was found that seed oil of HR markedly inhibited MDA formation of liver induced by CCl4, AAP and ethyl alcohol, seed oil 4.75 g/kg could lower SGPT levels induced by CCl4 and AAP. It blocked also depletion of GSH damaged liver induced by AAP. The mechanism of heptoprotective actions of HR seed oil might be related to anti lipid peroxidation. PMID- 1302198 TI - [Hygienic investigation and evaluation of houses of Turfan countryside in Xinjiang]. AB - Turfan Basin of Xinjiang is the hottest place in China. Hygienic investigation on two kinds of house in countryside and determination of indoor air quality were conducted. The physiological reaction of local people was also evaluated. The results showed that cave dwellings were warmer in the winter and cooler in the summer, but natural lighting and ventilation were poor. In the winter, indoor air pollution was more severe. The physiological responses of local people to two kinds of houses did not show any significant difference. PMID- 1302199 TI - [Potential risk of eating Pteridium aquilinum and its products]. PMID- 1302200 TI - Automated determination of oxytetracycline residues in muscle, liver, milk and egg by on-line dialysis and post-column reaction detection HPLC. AB - An automated method for control of oxytetracycline (OTC) residues in chicken and bovine muscle, salmon liver, bovine milk and hen egg has been developed. Tissue homogenate, decreamed milk or whole egg solution was dialysed and the dialysate enriched on a small polystyrene column on-line to HPLC. OTC and the internal standard (tetracycline) were separated on a polystyrene column by ion-pair chromatography. The column effluent was mixed with sodium hydroxide and irradiated at 366 nm. Monitoring the resulting derivatives with a fluorescence detector (excitation: 358 nm, emission: 460 nm), OTC could be detected at 1 ng/ml in milk, 1 ng/g in egg, 3-4 ng/g in muscle and 8 ng/g in liver. Relative standard deviations at 50 and 200 ng/g (milk: 20 and 100 ng/ml) ranged from 1.6 to 3.1%. PMID- 1302201 TI - Depletion of protein-bound furazolidone metabolites containing the 3-amino-2 oxazolidinone side-chain from liver, kidney and muscle tissues from pigs. AB - Ten 3-month-old pigs were treated with feed containing 300 mg furazolidone per kg for a period of 7 days, followed by withdrawal periods of 0, 1, 2, 3 or 4 weeks (two per group). The treatment resulted in the formation of protein-bound metabolites containing an intact 3-amino-2-oxazolidinone (AOZ) side-chain that could be chemically released and then detected in liver, kidney and rump muscle tissues even 4 weeks after dosing. In tissues from animals killed at the end of the medication period, 993, 600 and 124 ng of AOZ were released from 1 g of liver, kidney and muscle respectively. In the tissues of the animals killed after a further 4 weeks the corresponding levels were 41, 7 and 10 ng/g respectively. It may be concluded that long withdrawal periods prior to slaughter for human consumption are required for pigs treated with furazolidone, because of the long residence time of protein-bound AOZ and the possibility that it might be released from its protein-bound form in the stomach and subsequently be transformed into a hydrazine. PMID- 1302202 TI - Production of trichothecene mycotoxins by Australian Fusarium species. AB - Australian isolates of Fusarium species were grown on potato dextrose agar. Trichothecenes produced by these species were extracted by ethyl acetate followed by methanol and a silica gel column was used to clean-up the extract. The extracted samples were derivatized by acetylation with trifluoroacetic anhydride and the derivatives analysed by gas chromatography/mass spectrometry (GC/MS). Multiple ion detection was used to trace ions characteristic of the trichothecenes expected to be present. Quantitation of those found was based on a known mass of pentabromophenol that was added as an internal standard. Eight species of Fusarium (nineteen strains) were surveyed, of which three species, F. acuminatum, F. equiseti and F. sporotrichioides, produced the trichothecenes scirpentriol, diacetoxyscirpenol, neosolaniol, HT-2 toxin, T-2 toxin, T-2 tetraol and deoxynivalenol. Wheat samples were inoculated with four different species of Fusarium, F. acuminatum, F. equiseti, F. graminearum and F. sporotrichioides, and in these samples diacetoxyscirpenol, neosolaniol, HT-2 toxin and T-2 toxin were found. PMID- 1302203 TI - Natural occurrence of Fusarium mycotoxins of the 1990 barley crop in Korea. AB - During the barley harvest in June 1990, there was a great deal of rainfall and high humidity in the southern part of Korea, and natural occurrence of Fusarium mycotoxins was suspected in barley samples. The samples of undergrade barley were obtained from four provinces and analysed for the presence of deoxynivalenol (DON) and nivalenol (NIV) by gas chromatography and zearalenone (ZEN) by high performance liquid chromatography. Of 37 samples, 33, 37 and 10 were positive for DON, NIV and ZEN, respectively. The husked barley contained 29-677 ng/g for DON, 114-1546 ng/g for NIV and 183-1416 ng/g for ZEN. The naked barley contained 38 645 ng/g for DON, 85-4569 ng/g for NIV and 40-1081 ng/g for ZEN. The average concentration of NIV in naked barley was higher than that in husked barley, but the average concentration of DON in husked barley was higher than that in naked barley. The survey indicates that the 1990 barley crop in Korea was heavily contaminated with Fusarium mycotoxins. PMID- 1302204 TI - Occurrence of the mycotoxins ochratoxin A, zearalenone and deoxynivalenol in feed components. AB - The mycotoxin contamination of feed components used by the Dutch cooperative feed industry was surveyed to estimate the risk for animal production losses. Of 89 randomly and 6 selectively taken samples of raw materials harvested in 1988 and 1989 27% were contaminated with ochratoxin A (OCHRA), 31% with zearalenone (ZEA) and 20% with deoxynivalenol (DON). The mean content (microgram/kg) of all positive randomly taken samples was 18 (OCHRA), 62 (ZEA) and 630 (DON). The highest level (microgram/kg) for all samples was 120 (OCHRA) in barley, 3100 (ZEA) in corn cob mix and 1900 (DON) in maizegluten feed. The results of this survey show that feed components are often contaminated with mycotoxins. However, the contamination level could only sporadically cause production losses in animal husbandry. PMID- 1302205 TI - Do saxitoxin-like substances have a role in scombrotoxicosis? AB - Evidence is presented which establishes that mackerel fed in captivity can, by relay from contaminated shellfish via sand eels, accumulate paralytic shellfish poisons (PSP) in the edible flesh at a level (250 micrograms saxitoxin equivalents per kg) similar to that in the contaminated shellfish. Data from ELISAs performed independently in two laboratories show that commercial mackerel fillets which have been associated with incidents of scombrotoxicosis contained 0.02-1.30 micrograms saxitoxin equivalents per kg, concentrations some two to four orders of magnitude below that normally detectable by the mouse bioassay. The doses, expressed as saxitoxin equivalents, administered inadvertently during volunteer testing of such fillets ranged up to 0.5 ng/kg bw, at least four orders of magnitude less than the fatal oral dose for an adult. The doses associated with the rapid induction of nausea/vomiting and/or diarrhoea, 0.11-1.0 ng/kg bw, could not be distinguished from the doses which failed to produce such symptoms in susceptible volunteers (up to 0.5 ng/kg bw). Factors that might explain this lack of correlation between dose (saxitoxin equivalents) and volunteer response are discussed along with previously published reports of PSP relay through the food web. It is suggested that the relay of algal toxins, particularly PSP, but possibly in combination with diarrheic shellfish poisons, may be responsible for scombrotoxicosis. PMID- 1302206 TI - Monitoring sweetener consumption in Great Britain. AB - A comprehensive survey of the consumption of intense sweeteners in Great Britain in 1988 quantified the levels of usage of different sweeteners and identified their distribution between food categories and population subgroups. Saccharin was found to be the most widely used intense sweetener. Beverages were the most common source of intense sweeteners. The quantities consumed of all sweeteners were found to be below the Acceptable Daily Intake (ADI) values established by the Joint FAO/WHO Expert Committee on Food Additives, the European Commission Scientific Committee for Food or the UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. PMID- 1302207 TI - [Genetics and cancer]. PMID- 1302208 TI - [Penicillins and beta-lactamase inhibitors]. PMID- 1302209 TI - [The culture of the pharyngeal exudate. Observations on its routine use]. PMID- 1302210 TI - [An approach to re-evaluating fecal parasitological examinations]. PMID- 1302211 TI - [The adaptation of Cooper's mile test for students in the city of Mexico]. AB - The Cooper is test (running 1609 m) was applied to 1196 students, 15 to 17 years old, performed the Cooper's test (1609 m race). The scale, designed adequately for this sample of Mexican population, allows to judge the physical fitness by means of an easy and economical procedure. PMID- 1302212 TI - [The present and future of the medical profession]. PMID- 1302213 TI - [Indeterminacy in carcinogenesis, uncertainty in cosmogony, similitude in ignorance]. PMID- 1302214 TI - [Panaceas and talismans]. PMID- 1302215 TI - [The failure of success. Reflections on the epidemic of diabetes mellitus]. PMID- 1302217 TI - Tuberculous pleural effusion: a diagnostic problem. PMID- 1302216 TI - [The treatment of colonic and ovarian cancer with radioactive monoclonal antibodies against the CA l9-9 and CA 125 antigens]. AB - The age of monoclonal antibodies arose with the papers by Kohler and Milstein in 1975. By means of a fusion between a neoplastic cell with one which produced a specific antibody they obtained a hybrid or clonal cell. Five years later, Nadler et al issued the first report of a patient with lymphoma treated with monoclonal antibodies. After the first announcement, diverse research centers have reported the clinical results obtained in various neoplasias treated with radioactive monoclonal antibodies directed against antigens associated with neoplasias, as well as non-specific tumoral antigens, including lymphomas, melanomas and cancers of the colon, ovary and breast. PMID- 1302218 TI - Thymic histology in myasthenia gravis. AB - Histological features of resected thymuses of 18 patients with myasthenia gravis were evaluated. Thymoma were seen in 16.6% of the patients. In the non thymomatous group, thymic hyperplasia with follicle formation was seen in 33.3%, involuted thymus with occasional lymphoid follicle formation in 11.1%, thymitis with B cell infiltration in 16.6%, involuted thymus in 11.1% and normal thymus in 11.1% of patients. Immuno-histological staining for B and T lymphocytes delineated the group labelled as thymitis with B cell infiltration. Mast cell and eosinophils were frequently seen in thymuses with thymic hyperplasia with follicle formation and thymitis with B cell infiltration. Thymic hyperplasia with follicle formation was more frequent in young patients and these patients had better prognosis. PMID- 1302219 TI - Adenosine deaminase activity in pleural fluid--a diagnostic test of tuberculous pleural effusion. AB - Adenosine deaminase (ADA) activity in pleural fluids was studied in 47 patients with pleural effusion of different etiology. Patients were divided into two groups: Group I - Tuberculous pleural effusion (21 patients): Group II - Non tuberculous effusion (26 patients) and these included malignant pleural effusion (9 cases), synpneumonic pleural effusion (9 cases) and transudative pleural effusion (8 cases). The mean ADA activity was 64.67 IU/L +/- 21.68 in group I and 6.99 +/- 3.69 in Group II. Increased mean pleural fluid ADA activity in tuberculous pleural effusion was highly significant (p < 0.001) when compared with pleural effusion of non-tuberculous etiology. Based on lowest value of ADA activity found in tuberculous pleural effusion (30 IU/L), the test has a sensitivity and specificity of 1. PMID- 1302220 TI - Aetiological diagnosis in permanent residents of Punjab presenting with chest complaints and high peripheral blood eosinophilia. AB - Sixty-six permanent residents of Punjab, presenting with chest complaints and absolute eosinophil counts (AEC) over 2000 per cumm were investigated to find out the cause of high eosinophilia. Tropical pulmonary eosinophilia (TE) was responsible for high eosinophilia in 27 cases (40.9%), even in this region where filariasis is not endemic. Severe asthma (23 cases), allergic bronchopulmonary aspergillosis (ABPA-5 cases), drug reaction (2 cases) and chronic eosinophilic pneumonia (2 cases) in adults and ascariasis (6 cases) in children were other main causes of high eosinophilia. It is emphasized that all cases with high blood eosinophilia should not be labelled as cases of TE simply on the basis of AEC over 2000 per cumm. This is all the more important for non-filarial regions. Only a systematically conducted work up can clinch the correct diagnosis in such cases. PMID- 1302221 TI - Adrenocortical insufficiency in smear positive pulmonary tuberculosis. AB - We studied 40 patients with pulmonary tuberculosis. All were positive for acid fast bacilli (AFB) in the sputum. Their mean age was 30 yrs (range 10-50 yrs) and the duration of illness was 26.3 +/- 2.3 months. Radiologically minimal, moderately advanced and far advanced lesions were present in 7 (17.5%), 9 (22.5%) and 23 (57.5%) patients respectively. One patient with endobronchial lesion had no radiological evidence of pulmonary tuberculosis. Clinically, 14 patients (35%) had one or the other features of adrenocortical insufficiency. Postural hypotension was the commonest feature and was present in 11 patients (27.5%), followed by nausea and vomiting (20%), loss of axillary hair and libido (10%), skin and mucosal pigmentation in 7.5% of the cases. ACTH stimulation revealed incomplete adrenocortical insufficiency (partially responsive adrenal) in 5 patients (12.5%) and complete adrenocortical insufficiency (non-responsive adrenal) in 2 patients (5%). Patients with features of adrenal insufficiency had significantly longer duration of illness (p < 0.001) but there was no correlation with extent or type of lesion. PMID- 1302222 TI - Effect of treatment on pulmonary functions in chronic severe anaemia. AB - Pulmonary functions were measured in 15 patients with severe chronic anaemia (haemoglobin level < 5 g/dl). The measurements were repeated after correction of anaemia (Hb > 10 g/dl). Twenty age and sex matched, asymptomatic, non-smoker subjects served as controls. There was 80-100% improvement in various lung functions after correction of anaemia. Effort dependent parameters, viz FVC, ERV, IC, MVV were low in anaemic patients which improved with the rise of haemoglobin. The TLCO, DM, VC, KCO were not significantly influenced during anaemic state. FEV1, PEFR, RV/TLC were essentially normal. We conclude that the observed changes produced in lung functions during anaemic state are fully reversible after its correction. PMID- 1302223 TI - Congenital asymptomatic absence of pericardium. AB - An interesting congenital anomaly of the pericardium is its absence. One such case is reported here. Recent literature is reviewed also. PMID- 1302224 TI - Domiciliary mechanical ventilation in a patient with severe chronic obstructive lung disease and respiratory failure. AB - A patient of chronic obstructive pulmonary disease (COPD) with cor-pulmonale and chronic respiratory failure, who was given intermittent positive pressure ventilation at home, is reported. The patient did remarkably well on home mechanical ventilatory support. We believe this to be the first case report of domiciliary mechanical ventilation in a patient of COPD from India. PMID- 1302225 TI - Posterior mediastinal teratoma. AB - A patient with benign posterior mediastinal teratoma which is a rare site for teratomas is reported. Chest skiagram and CT of the thorax established the diagnosis. Complete removal of the mass was not possible on surgery as it was adherent to the pericardium and the esophagus. The patient remained asymptomatic one year after the surgery. There was no evidence of recurrence of the tumor. PMID- 1302226 TI - Unilateral pulmonary edema--a report of two cases. AB - We report two cases of unilateral pulmonary edema, one in patient with chronic renal failure which was mistaken for pulmonary tuberculosis and the other in a patient with congestive heart failure. We have reviewed the relevant literature. PMID- 1302227 TI - Orbit--the often omitted structure by ophthalmic surgeons. PMID- 1302228 TI - Selective suture cutting for control of astigmatism following cataract surgery. AB - Use of 10-0 monofilament nylon in ECCE cataract surgery leads to high with the rule astigmatism. Many intraoperative and post operative methods have been used to minimise post operative astigmatism. We did selective suture cutting in 38 consecutive patients. Mean keratometric astigmatism at three and six weeks post operative was 5.76 and 5.42 dioptres (D) respectively. 77.5% of eyes had astigmatism above 2 D. Selective suture cutting along the axis of the plus high cylinder was done after six weeks of surgery. Mean post suture cutting keratometric astigmatism was 3.3 D and 70% of the eyes had astigmatism below 2 D. After 3 months of surgery mean keratometric astigmatism was reduced to 1.84 D. Axis of the astigmatism also changed following suture cutting. 40% of the eyes showed improvement in their Snellen acuity following reduction in the cylindrical power. PMID- 1302229 TI - Maximal mydriasis evaluation in cataract surgery. AB - We propose the Maximal Mydriasis Test (MMT) as a simple and safe means to provide the cataract surgeon with objective and dependable pre-operative information on the idiosyncratic mydriatic response of the pupil. The MMT results of a consecutive series of 165 eyes from 100 adults referred for cataract evaluation are presented to illustrate its practical applications and value. The results of the MMT allows the surgeon to anticipate problem eyes pre-operatively so that he can plan his surgical strategy more appropriately and effectively. Conversely, the surgeon can also appropriately and confidently plan surgical procedures where wide pupillary dilation is important. The MMT has also helped improve our cost effectiveness by cutting down unnecessary delays in the operating room and enabling better utilisation of restricted costly resources. PMID- 1302230 TI - Clinico-immunological aspects of vernal catarrh in hilly terrains of Himachal Pradesh. AB - Very few immunological studies in vernal catarrh have been conducted in India and abroad, but none in Himachal Pradesh in spite of its high incidence in the State. In the present study 25 patients of vernal catarrh residing at a height ranging between 1000 to 2500 meters above mean sea level have been evaluated. Their immunological status of serum and tears after detailed clinical assessment was studied by single radial immunodiffusion technique of Mancini et al. The values of serum IgA and IgM were significantly higher in patients than in controls. The serum IgE level had no significant difference. The IgG was significantly lower in patients with vernal catarrh. The values of tear IgM, IgE and IgA in these patients were significantly higher than in controls. However, in no case or control group C3C and C4 were detected in tears. The limbal type of vernal catarrh was found to be the most common in this part of the country. No mixed case was seen. Derangement of the immune system in the pathogenesis of vernal catarrh is suggested. PMID- 1302231 TI - Role of orthoptic treatment in the management of intermittent exotropia. AB - 30 patients of intermittent ACDS were studied prospectively for a period of 8 weeks to 1 year to evaluate the role of orthoptics in the management of these cases. In patients with convergence insufficiency and a maximum deviation of 25 PD or less the orthoptic treatment was found to be effective in offering symptomatic relief and improving binocular functional status. A reduction in the maximum angle of deviation by 4 PD to 8 PD was observed in 4 patients. Even though the basic angle of deviation remained unchanged in most of the patients, significant functional and symptomatic improvement was obtained in 64% to 85.7% of these cases. The long term stability of these results remains to be studied. In patients with a deviation of more than 25 PD there was no significant improvement in symptoms or reduction in maximum angle of deviation. In 6(37.5%) of these patients some improvement in the fusional range could be demonstrated on the synoptophore without any symptomatic relief. PMID- 1302232 TI - Blepharoptosis repair by modified sutureless Fasanella-Servat Operation (F.S.O)- a large series of 50 cases. AB - A modified technique of sutureless Fasanella-Servat Operation (F.S.O.) using special curved haemostat for the correction of mild to moderate acquired ptosis with good Levator Palpebrae Superioris (L.P.S.) action (12 m.m.) was performed in a large series of 50 eyes. Excellent correction was achieved in 94.6% eyes with mild ptosis & 61.6% eyes with moderate ptosis. No operative and post operative complications were observed. The technique was found to be very safe, quick and effective. PMID- 1302233 TI - Tuberculoma of orbit. AB - An interesting case of tuberculoma of the orbit, involving the whole of the eyeball with other orbital cavity structures, is being presented. This is very rarely seen in clinical practice. PMID- 1302234 TI - Mesenchymal chondro sarcoma of orbit with intra cranial extension (a rare case). PMID- 1302235 TI - An unusual orbito-cranial foreign body. AB - The rarity of orbito-cranial gun shot injury in both war and civilian practice has been reported. In a large series of 351 missile head injuries in the Vietnam war, orbital penetration was noted in 0.6% cases only. Review of literature shows that orbital injury was ipsilateral to the cerebral injury in most reported cases. We have previously reported a rare case of left parieto-occipital lobe injury due to gun shot wound of the contralateral (right) orbit. The case reported here sustained a bullet injury to the left frontal bone but the missile was located below the contralateral (right) optic canal. The rarity of the case prompted this report. PMID- 1302236 TI - Bilateral acute retinal necrosis--a case report. AB - A 42 year old man presented with acute bilateral uveitis and necrotizing retinitis. Systemic investigations including test for AIDS and CMV retinitis were negative. Despite oral Acyclovir, both eyes progressed rapidly to retinal detachment with loss of vision. Early recognition is necessary to diagnose the bilateral acute retinal necrosis syndrome and initiate treatment. Bilateral acute retinal necrosis (BARN) is a term first coined by Young and Bird in 1978 although the syndrome had been originally described by Urayama et al as an unilateral condition. This syndrome is characterized by the triad of acute confluent peripheral necrotizing retinitis, moderate to severe vasculitis and vitritis in an otherwise healthy individual. Rhegmatogenous retinal detachment occurs within two to three months of the onset of the disease and the second eye is involved in 36% of patients, usually within 6 weeks. We herein report a patient who presented with simultaneous BARN leading to retinal detachment in a matter of days. Also, to our knowledge this is the first report of this condition in India. PMID- 1302237 TI - Colours for your eyes. PMID- 1302238 TI - [Legal information]. PMID- 1302239 TI - The 1992-93 general supervision of the practice of the nursing assistant profession program. PMID- 1302240 TI - Events which will have a decisive influence over the nursing assistant profession. PMID- 1302241 TI - Councils of Nursing Assistants (N.A.C's) PMID- 1302242 TI - Modernization and status change among aged men and women. AB - This study investigates the differences between the relationship between elderly occupational status and modernization for men and women. Consonant with previous findings, it finds that economic development is associated with relative losses of elderly men in professional and technical occupations. Augmenting those findings, however, it finds an even stronger association between development and such losses for women. In accounting for the differences, several explanations are advanced and tested, using data from fifty-one nations. PMID- 1302243 TI - Outcomes of equity/inequity among older spouses. AB - The extent to which perceptions of global and specific equity/inequity were associated with dissatisfaction, disagreement between spouses, partners' regard for one another, and gender-role attitudes was investigated for eighty-two couples over age sixty. The differential influence of equity/inequity for the well-being of women and men was studied. PMID- 1302244 TI - The concept of compensation in cognitive aging: the case of prose processing in adulthood. AB - Although the rule of cognitive aging appears to be one of generalized decline with advancing age, much recent theoretical and empirical work has addressed a variety of potential exceptions to this rule. One mechanism through which decline might not be experienced is known as compensation. We describe a conceptualization of compensation that applies to lifespan cognitive development, in general, and the aging of prose processing skills, in particular. Our model of the forms and processes of compensation directs attention to the developing dynamics of cognitive skills and compensatory mechanisms. We outline three main approaches to research on compensation in cognitive aging: a) the logical experimental, b) on-line observation and manipulation, and c) several verbal report procedures. In summarizing our own research program, we emphasize that a) each of these approaches can render valuable information, b) each have some limitations, and c) there are potential theoretical benefits from employing more than one of them in a given study. PMID- 1302245 TI - Perceived control and adaptation in elder caregivers: development of an explanatory model. AB - Perceived control has been implicated in the adaptation and well-being of older adults and may be especially relevant to elder caregivers. However, few studies have investigated perceived control within the individual's unique personal, social, and environmental context. This study tested a model representing the hypothesis that perceived control, defined as the perception that salient or valued aspects of one's life are manageable, mediates the objective and subjective aspects of caregiving and caregiver adaptation. Sixty elderly caregivers ranging in age from sixty to eighty-four (M = 69.4) were interviewed. Perceived control had a direct relationship with life satisfaction and depression, and an indirect relationship with subjective symptoms of stress. Wishful thinking coping behavior had a negative relationship with all adaptation variables. Findings are discussed in relation to further refinement and development of a theoretical approach to caregiver research and intervention studies in light of the obtained path model. PMID- 1302246 TI - Experimental intercomparisons of younger and older driver perceptions. AB - Drivers over sixty-five years of age and drivers under twenty-one years of age have the highest relative frequency of crashes resulting in injury and death. Attitudes of these two groups were investigated using questionnaires. One hundred twenty-seven (127) younger and one hundred eight (108) older drivers who had voluntarily registered in driving education courses satisfactorily completed questionnaires about attitudes and behaviors pertinent to safe driving. Half of each sample rated the average driver in their age group and the average driver in the opposite age group as regarded thirty-three attitudes promoting safe driving, twenty courteous safe driving behaviors and eleven discourteous, unsafe driving behaviors. Data shows that younger drivers viewed older drivers as overly cautious, too slow to act and apt to cause accidents, and rated their peers as overly aggressive and discourteous. Older drivers characterized younger drivers as deficient in courtesy and safe driving practices, and they rated their peers as cautious, courteous, and aware of age-related limitations. The findings indicate that each group was aware that safety hazards are created by drivers in their age group. It also shows that both groups had a positive impression of some driving practices of their age group, and that the other group was depreciated. The outcome confirms and expands upon conclusions derived from less formal studies about how drivers perceive other roadway users. It also specifies the extent to which particular attitudes and driving practices are attributed to the peer group and to the opposite age group. PMID- 1302247 TI - Analysis of retroviral proteins by two-step DNA, zinc binding, and modified Southern-western blotting. AB - Using Southern-Western and zinc-blotting techniques, the interactions of single stranded DNA and zinc with structural proteins of type B, C, and D retroviruses were examined. Besides nucleic capsid proteins of retroviruses known to form complexes with nucleic acids, some other core proteins of type C retroviruses were shown to bind nucleic acids. All nucleic capsid proteins of the examined retroviruses appeared to be also zinc binding. In the present report, we propose two protein-blotting techniques that could be performed on a single nitrocellulose membrane. A first technique allows to detect zinc- and DNA-binding proteins immobilized on the membrane; a second (a modification of Southern Western blotting) makes it possible to detect DNA-binding proteins followed by immunological reprobing. PMID- 1302248 TI - Molecular cloning and restriction enzyme analysis of bovine adenovirus type 3. AB - Bovine adenovirus type 3 (BAV3) is a DNA virus that causes respiratory and gastrointestinal disorders in cattle. The viral genome consists of a linear double-stranded DNA molecule (35,000 base pairs) with inverted terminal repeats at each of its 5' molecular ends. We have subcloned 10 HindIII fragments spanning 4.9-96.0%, 5 EcoRI fragments spanning 3.4-89.5% and 2 XbaI fragments spanning 35.7-82.9% of the BAV3 (strain WBR-1) genome into the bacterial cloning vector pUC19. The subcloning of the viral genome facilitated the construction of linear restriction enzyme maps for BamHI, ClaI, EcoRI, HindIII, KpnI, NotI, NspV, PstI, PvuI, SalI, XbaI and XhoI. In this study we report on the molecular cloning and restriction endonuclease mapping of the BAV3 genome. PMID- 1302249 TI - Computerization of virus data and its usefulness in virus classification. AB - Data on 537 Arboviruses and 180 other viruses have been collected and coded in two different formats. These data include information not only regarding the taxonomy and history of isolation, but also regarding the properties of biomacromolecules, proteins and nucleic acids. Information on antigenic relationships, histopathology and experimental viremia is also included. This information is stored in formats which allow the manipulation and analysis of data by dBASE III PLUS and MICRO-IS. A set of programs was written for interconversion and editing purposes. Transmission electron micrographs are scanned and stored. This stored information can be used in viral classification as shown by carrying out analysis of data on the Bunyaviridae family. PMID- 1302250 TI - Koolpinyah: a virus related to kotonkan from cattle in northern Australia. AB - Two closely related viruses were isolated from the blood of bovines near Darwin, Northern Territory, Australia. When studies of virus morphology indicated that these were rhabdoviruses, serologic studies were done. These isolates are closely related or identical and are related to, but distinct from, the rabies-related kotonkan virus. Other serologic studies showed that these are two isolates of a newly recognized virus, for which the name Koolpinyah virus is proposed. PMID- 1302251 TI - Self-efficacy: a predictor but not a cause of behavior. AB - The concept of self-efficacy, as expounded by Bandura as part of his Social Cognitive Theory, has made considerable impact in the psychological literature. It is argued that self-efficacy is a useful hypothetical construct for predicting behavior, but it has no valid claim to being a cause of behavior. Claims for self efficacy as a causal agent have failed to acknowledge that self-efficacy itself is an epi-phenomenon of performance. Conventional learning theory explanations of observed performance levels are shown to be more parsimonious than accounts relying on the concept of self-efficacy. PMID- 1302252 TI - On cognitive theories and causation in human behavior. AB - Modern theories of social behavior are based on the largely unquestioned assumption that human activity is determined by cognitive variables. Physiology, environment, and behavior are seen as peripheral to the understanding of cognition, seen as central to the understanding of human nature. This paper argues that these approaches to psychology are essentially metaphorical models of behavior, inadequate as explanatory theories, because they rely on untestable assumptions concerning the centrality to human behavior of hypothetical and unmeasurable cognitive variables. Their lack of precision does not allow for the testing of specific predictions. This paper argues that contemporary cognitive behavioral and cognitive-social theories cannot be salvaged as explanatory models. PMID- 1302253 TI - Physically aggressive elderly: a social skills training program. AB - The present investigation utilized a social skills training program to eliminate physically aggressive behavior in a group of six institutionalized elderly patients. The treatment package consisted of instructions, modeling, role playing and feedback. Dependent measures included confirmed incidents of physically aggressive behavior monitored across an ABAB design with a 5-month follow-up period. Results indicated that physically aggressive behavior can be significantly decreased in a group training setting and subsequently generalized to ward and other socialized behavior. Ancillary aspects of the study include the differential properties associated with physical and verbal aggression, the role of vicarious reinforcement on behavior, and generalization effects. PMID- 1302254 TI - Assessment and prediction of outcome for a brief behavioral insomnia treatment program. AB - This study examined (a) the efficacy, and (b) predictors of outcome of a brief (one to four sessions) behavioral treatment program for chronic insomnia. A total of 103 insomnia patients were treated, and outcome was assessed by a follow-up questionnaire. Outcome variables, including both nocturnal sleep parameters and measures of daytime functioning, showed significant improvement subsequent to treatment. Pretreatment sleep hygiene practices were significantly correlated with daytime fatigue and sleep latency outcome factors. Pre- and post-treatment complaints of daytime fatigue were associated with somatic complaints in general, but not with nocturnal sleep variables. Explanatory hypotheses are discussed. PMID- 1302255 TI - The possible function of positive reinforcement in home-bound agoraphobia: a case study. AB - We conducted an uncontrolled case study (ABA design) based upon the hypothesis that the behavior of a home-bound agoraphobic is at least partially maintained by positive reinforcement in the home and that a disruption of access to home-based reinforcement would lead to an increased frequency of out-of-the-home behavior. Data concerning the types and amounts of behavior engaged in by the subject within the confines of her home and yard were gathered during a 30-day base line period. In addition, potential reinforcers in the home were identified by a survey schedule and by self-report of time allocation. During an 18-day intervention period the subject agreed only to engage in certain reinforcing activities outside her home (e.g., only watching television at a neighbor's house). Postintervention results indicated that for the first time in over 7 years the subject began engaging in out-of-home activities, including walking to other parts of the street, visiting several neighbors' homes, and attending parties at neighbors' homes. Moreover, data suggested a positive trend in time spent outside the yard during both 2 and 18 month follow-up periods. However, significant restrictions in the range of mobility were still observed. PMID- 1302256 TI - The treatment of bulimia nervosa following surgery using a stimulus control procedure: a case study. AB - This single case report describes the treatment of a 35-year-old female, who was diagnosed as suffering from severe bulimia nervosa. Of interest were the frequent vomiting episodes which did not exist prior to two surgical operations performed on the client in order to reduce her overall body weight. The treatment, a stimulus control procedure, which spanned 20 sessions, lasted about 24 weeks and was deemed successful after a year follow-up. Of primary importance was the self management aspect of the treatment program, which emphasized minimum therapist intervention. In addition, there was a complete absence of "cognitive components" deemed necessary by some authors for the long-term treatment success of bulimics. Different factors relating to the success of this treatment program are also reviewed. PMID- 1302257 TI - Cyclical self-injurious behavior, contingent water mist treatment, and the possibility of rapid-cycling bipolar disorder. AB - Cyclical self-injurious behavior (SIB) in the form of self-slapping was treated in a 45-year-old, profoundly retarded woman who had a life-long history of SIB. Her SIB alternated between high (mean = 8.54 responses per min; SD = 6.77 and low (mean = 0.05 responses per min; SD = 0.20) frequencies every 8 weeks on average. Instances of self-slapping produced water mist treatment paired with a verbal command, "No hitting". Absence of self-slapping and/or completion of a work task led to a variety of outcomes, including brief back rubs, sips of water, small edibles, and praise. Water mist treatment reduced the frequency of SIB within treatment days during high frequency periods, but produced no reduction across treatment days. Treatment onset was associated with a slight increase in the frequency of SIB during three of the five low frequency periods. However, water mist treatment suppressed SIB completely in sessions during low frequency periods and the suppression continued across treatment days. Water mist treatment produced no discernible changes in the length of the high and low frequency periods of SIB. PMID- 1302258 TI - Hyperoxemia profoundly alters breathing pattern and arouses the fetal sheep. AB - We have recently shown that hyperoxemia alone or combined with umbilical cord occlusion causes continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). We have not however analyzed the changes in the pattern of breathing associated with these events. To do this, we measured the changes in breathing pattern, electrocortical activity and behaviour on 29 occasions in 15 fetal sheep in late gestation. Fetuses were studied during rest, and during lung distention (about 30 cm H2O) with 100% nitrogen (control), 17% oxygen, 100% oxygen and umbilical cord occlusion. Lung distention was obtained using a high frequency oscillator (Senko Co) and in some fetuses a stroke volume of 0 to 20 cm H2O was used to keep PaCO2 near-constant. We found that lung distention with nitrogen or 17% oxygen did not alter the pattern of breathing or behaviour. In 12 out of 34 (35%) experiments 100% oxygen induced continuous breathing, PaO2 increasing to about 250 torr. In the remaining 22 experiments, PaO2 increased to about 100 torr only and breathing was not continuous but it became continuous upon cord occlusion; with occlusion there was a further increase in PaO2 to 190 torr. The increased breathing with oxygen and occlusion was associated with an increase in breathing output (integral of EMGdi x f), an increase in inspiratory drive (integral of EMGdi/Ti), and a decrease in inspiratory (Ti) and expiratory (Te) times. In ten experiments PaCO2 was kept near-constant and the magnitude of the changes remained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302259 TI - Neuropeptide Y and catecholamine release in the piglet during hypoxia: enhancement by theophylline. AB - Sympathoadrenal activity was studied in 13 young piglets during hypoxia. The piglets were anaesthetized with chloralose/urethane, tracheostomized, paralyzed with gallamine and artificially ventilated. A femoral artery catheter was inserted and used for blood sampling. The piglets were challenged with 6 min of 6% CO2, 10 min of 12% O2 and 6 min of 6% O2 before and after theophylline (an adenosine receptor antagonist) treatment 20 mg/kg (n = 9) or saline (n = 4). Plasma samples were obtained before, during and after each hypercapnic or hypoxic period and analysed for their content of noradrenaline, adrenaline and neuropeptide Y. Hypercapnia with 6% CO2 and moderate hypoxia with 12% O2 did not lead to any significant increase of either noradrenaline (NA), adrenaline (A) or neuropeptide Y (NPY). However, severe hypoxia with 6% O2 increased the NA level from 30 to 66 nmol/l; the A level from 1 to 28 nmol/l and NPY from 140 to 213 pmol/l. After treatment with theophylline the baseline NA increased from 27 to 40 nmol/l, A rom 1.5 to 4.0 and NPY concentration from 65 to 171 pmol/l. Theophylline moderately enhanced the release of NPY, NA and A during the 12% O2 challenge. However, during the severe hypoxia (6%), the increase of NA (from 49 to 333 nmol/l), A (from 8 to 214 nmol/l) and NPY (from 184 to 385 pmol/l) showed considerably enhancement after the theophylline treatment. The results obtained before and after saline were similar showing that the duration of the experiments per se did not change the baseline levels or the effect of the challenges on NA, A or NPY levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302260 TI - Effects of tetrodotoxin, Ca2+ absence, d-tubocurarine and vesamicol on spontaneous acetylcholine release from rat muscle. AB - 1. Rat hemidiaphragms were incubated in a physiological low-K+ medium without stimulation and the amount of acetylcholine (ACh) released was measured radioenzymatically. Cholinesterases were inhibited by paraoxon. 2. In the presence of 1 microM tetrodotoxin (TTX), the amount of ACh released during a 2 h incubation was lowered by 40%. A similar decrease was observed in the absence of Ca2+ and in the presence of 10 microM-d-tubocurarine (dTC). The effects of TTX combined with Ca2+ removal, and of TTX combined with dTC were no greater than those of TTX, dTC or Ca2+ removal alone. TTX and dTC had no effect on the release of ACh from diaphragms 4 days after denervation. 3. The reduction of spontaneous ACh release observed in the presence of TTX or dTC or in the absence of Ca2+ is best interpreted on the assumption that about 40% of the ACh release was due to the impulse activity known to be generated in intramuscular motor nerve branches by the ACh which accumulates after the inhibition of cholinesterases. 4. In the presence of 1 and 10 microM vesamicol (AH5183, 2-(4-phenylpiperidino) cyclohexanol), the release of ACh was also diminished by approximately 40%. Vesamicol did not augment the inhibition of release produced by TTX or by the omission of Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302261 TI - Tension responses of sheep aorta to simultaneous decreases in phosphocreatine, inorganic phosphate and ATP. AB - 1. Tension responses of sheep aortae were investigated when different substrates were included in the superfusing medium. The magnitude of tension development was similar whether or not 5 mM glucose was present in the medium. However, the rate of tension development was greater in the absence of glucose. 2. When 5 mM 2 deoxyglucose (2DG) was present in the medium, the magnitude of tension generation was 1.6 times that in the absence of exogenous substrate. A second sequential contraction with 2DG generated tension 1.25 times that in the absence of exogenous substrate. The rate of tension development during the first contraction in the presence of 2DG was similar to that in the absence of substrate. However, the second contraction in the presence of 2DG had a substantially increased rate of tension development. 3. 31P nuclear magnetic resonance (NMR) spectroscopy revealed that, at resting tone, in the presence of 2DG, inorganic phosphate (P(i)) and phosphocreatine (PCr) simultaneously decrease while 2-deoxyglucose-6 phosphate accumulates. During contraction-relaxation cycles, in the presence of 2DG, P(i) and PCr become undetectable while ATP declines to approximately 50% of control values as determined by NMR. During the second contraction in the presence of 2DG, the area of the ADP resonance was similar to that of the alpha ATP resonance. 4. The increase in the magnitude of tension generation, during 2DG administration, correlated with a decrease in P(i) levels. The rate of relaxation from a contraction, in the presence of 2DG, was slower than in the presence of glucose or in the absence of exogenous substrate. These results are consistent with the role of P(i) in the release of the proposed 'latch-bridge' state of maintained contraction at low energy demand. 5. The increase in isometric tension generation during contraction in the presence of 2DG appears to be related to the decreased levels of P(i). In the presence of 2DG, the reduction of PCr and of ATP occur to a similar extent to that during hypoxia, yet no inhibition of force takes place. The low levels of ATP and PCr reported with 2DG administration in these studies do not energetically limit the contractile apparatus. PMID- 1302262 TI - Responses of slowly adapting type II afferent fibres in cat hairy skin to vibrotactile stimuli. AB - 1. Slowly adapting type II (SAII) afferent fibres that supply the forelimb were isolated from the medial cutaneous nerve of anaesthetized cats and examined for their capacity to signal information about vibrotactile events in the hairy skin. 2. The SAII fibres had a single spot-like receptive field focus where they were highly sensitive to steady indentation and vibration applied with probes normal to the skin surface. However, their sensitivity was affected profoundly by the size of the stimulus probe, its position in relation to the receptive field focus and, to a lesser extent, the magnitude of any pre-indentation on which vibration was superimposed. Small stimulus probes (e.g. 250 microns diameter) were much more effective than larger (> or = 1-2 mm) ones, and small shifts in the position of the perpendicularly applied probe away from the receptive field focus led to a marked decline in responsiveness. 3. With appropriate choice of stimulus parameters for vibratory stimuli applied at the receptive field focus, the SAII fibres could respond at low threshold (< 100 microns), with a tightly phase locked, regular 1:1 impulse pattern (one impulse per vibration cycle) that accurately signalled the vibration frequency over a bandwidth that extended to 600 Hz. Furthermore, their responses remained phase-locked up to 1000 Hz. Phase locking in SAII fibres was marginally tighter than that in SAI fibres and comparable to that of Pacinian corpuscle fibres. 4. The sensitivity of forelimb SAII fibres to tangential skin stretch was directionally selective; stretch across the forelimb was much more effective than along its long axis. Vibration associated with tangential skin stretch led to a marked spatial expansion of the field of vibration sensitivity. SAII fibres could therefore signal information about natural stimuli that contain elements of skin stretch and vibration, as may be encountered when the forelimb brushes against textured surfaces. Should the SAII fibres fail to contribute to the sensory experience of vibrotactile stimuli, the explanation may be related to limitations imposed centrally on the processing of their signals. Nevertheless, the present results demonstrate that, with appropriate stimulus conditions, the SAII afferent fibres have much greater vibrotactile sensitivity than has been suggested by past studies. PMID- 1302263 TI - Intracellular calcium dynamics in response to action potentials in bullfrog sympathetic ganglion cells. AB - 1. Dynamic changes in the intracellular free Ca2+ concentration ([Ca2+]i) following electrical membrane activity, were recorded from the neurone soma of the excised bullfrog sympathetic ganglion, using Fura-2 fluorescence and compared with the accompanying Ca(2+)-dependent electrical membrane responses. 2. The resting [Ca2+]i was about 100 nM, a value little changed by penetration with an intracellular electrode. 3. A net rise in fluorescence at a wavelength of 340 nm (Ca2+ transient) induced by a single action potential in Ringer solution rose almost in parallel with the initial decay phase of a slow Ca(2+)-dependent after hyperpolarization; decayed in parallel with the late phase; and increased in amplitude and duration in the presence of tetraethylammonium (20 mM). 4. A Ca2+ transient induced by repetitive action potentials was increased asymptotically in amplitude and progressively in duration by increasing the number of spikes, and was slower in time course than the associated Ca(2+)-dependent K+ current. 5. Scanning a single horizontal line across the cytoplasm with an ultraviolet argon ion laser (351 nm) and recording Indo-1 fluorescence with a confocal microscope demonstrated an inward spread of a rise in [Ca2+]i following a tetanus. 6. Both single spike- and tetanus-induced Ca2+ transients were abolished in a Ca(2+)-free solution, while single or repetitive transient rises in [Ca2+]i induced by caffeine (5-10 mM) were generated under the same conditions. 7. Ryanodine (10-50 microM) did not affect tetanus-induced Ca2+ transients, whereas it blocked completely the caffeine-induced oscillation of [Ca2+]i. 8. Ca2+ transients induced by a tetanus in Ringer solution were independent of the interval from the preceding tetanus. The amplitude of Ca2+ transients induced by a tetanus in the presence of caffeine (5 mM) was equal to, or greater than, that generated in Ringer solution in any of the phases of [Ca2+]i oscillation. 9. It is suggested that under the physiological conditions here, the induction of action potentials does not cause the release of Ca2+ in the cells of the freshly excised bullfrog sympathetic ganglion, and that Ca(2+)-buffering systems contribute not only to lowering a transient rise in [Ca2+]i but also to sustaining an increased [Ca2+]i after a large Ca2+ load into the cell. PMID- 1302264 TI - Responses of macaque ganglion cells to the relative phase of heterochromatically modulated lights. AB - 1. We measured the response of macaque ganglion cells to sinusoidally modulated red and green lights as the relative phase, theta, of the lights was varied. 2. At low frequencies, red-green ganglion cells of the parvocellular (PC-) pathway with opponent inputs from middle-wavelength sensitive (M-) and long-wavelength sensitive (L-) cones were minimally sensitive to luminance modulation (theta = 0 deg) and maximally sensitive to chromatic modulation (theta = 180 deg). With increasing frequency, the phase, theta, of minimal amplitude gradually changed, in opposite directions for cells with M- and L-cone centres. 3. At high frequencies (at and above 20 Hz), phasic cells of the magnocellular (MC-) pathway were maximally responsive when theta approximately 0 deg and minimally responsive when theta approximately 180 deg, as expected from an achromatic mechanism. At lower frequencies, the phase of minimal response shifted, for both on- and off centre cells, to values of theta intermediate between 0 and 180 deg. This phase asymmetry was absent if the centre alone was stimulated with a small field. 4. For PC-pathway cells, it was possible to provide an account of response phase as a function of theta, using a model involving three parameters; phases of the L- and M-cone mechanisms and a L/M cone weighting term. For red-green cells, the phase parameters were monotonically related to temporal frequency and revealed a centre-surround phase difference. The phase difference was linear with a slope of 1-3 deg Hz-1. If this represents a latency difference, it would be 3-8 ms. Otherwise, temporal properties of the M- and L-cones appeared similar if not identical. By addition of a scaling term, the model could be extended to give an adequate account of the amplitude of responses. 5. We were able to activate selectively the surrounds of cells with short-wavelength (S-) cone input to their centres, and so were able to assess L/M cone weighting to the surround. M- and L cone inputs added linearly for most cells. On average, the weighting corresponded to the Judd modification of the luminosity function although there was considerable inter-cell variability. 6. To account for results from MC-pathway cells, it was necessary to postulate a cone-opponent, chromatic input to their surrounds. We developed a receptive field model with linear summation of M- and L cones to centre and surround, and with an additional M,L-cone opponent input to the surround.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302265 TI - Asymmetry of vascular responses of perfused rabbit carotid artery to intraluminal and abluminal vasoactive stimuli. AB - 1. Responses of the carotid artery of rabbits to intraluminal and abluminal administration of purinergic agonists were examined. The carotid artery was perfused in vitro and changes in diameter were recorded. 2. Intraluminal acetylcholine, ADP, and ATP produced pronounced vasodilatation, whereas abluminal acetylcholine, but not ADP and ATP, produced dilatation of phenylephrine preconstricted arteries. Intra- and abluminal adenosine and nitroprusside produced equipotent vasodilatation. 3. N omega-nitro-L-arginine abolished dilator responses to acetylcholine and adenine nucleotides, and unmasked vasoconstrictor responses to high concentrations of these agonists. Responses to adenosine and nitroprusside were not affected by nitro-L-arginine. 4. Intraluminal, but not abluminal, administration of nucleotidase-resistant adenine nucleotide analogues 2-methylthio-ATP and ADP beta S produced significant vasodilation in arteries preconstricted with phenylephrine. Intra- and abluminal administration of alpha,beta-methylene-ATP, a potent P2X-purinoceptor agonist, did not produce vasodilatation in preconstricted arteries. 5. Abluminal ADP failed to elicit dilatation of phenylephrine-preconstricted arteries even in the presence of the ADPase inhibitor beta,gamma-methylene-ATP (10(-5)M). When P2X-purinoceptors, which mediate adenine nucleotide-induced vasoconstriction, were stimulated with alpha,beta-methylene-ATP (10(-5)M), abluminal ADP produced vasodilatation, presumably because P2X-purinoceptors were occupied, thereby unmasking P2Y purinoceptor-mediated dilatation. 6. These results suggest that asymmetric vascular responses of rabbit carotid arteries to adenine nucleotides may be due in part to preferential activation of P2Y-purinergic receptors on endothelium and P2X-purinergic receptors on vascular smooth muscle. PMID- 1302266 TI - Convergence of visceral and somatic inputs onto subnucleus reticularis dorsalis neurones in the rat medulla. AB - 1. In anaesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurones that exhibited convergence of nociceptive inputs from the entire surface of the body. Neurones with total nociceptive convergence responded to supramaximal percutaneous electrical stimuli (2 ms duration) with early and late peaks due to the activation of A delta and C fibres, respectively, no matter which part of the body was stimulated. Neurones with partial nociceptive convergence responded to identical stimuli with an A delta peak of activation regardless of which part of the body was stimulated and with a C peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurones to graded colo-rectal distension (< or = 100 mmHg) were analysed. 2. The majority of neurones with total nociceptive convergence (n = 13 out of 16) responded to colo-rectal distension by increasing their firing rates. Although these neurones were virtually unresponsive to the lowest pressure employed (12.5 mmHg), they increased their discharges monotonically for distensions in the 26-100 mmHg range and these responses were sometimes followed by after-discharges. One of these neurones, which exhibited a high level of spontaneous activity, was inhibited during colo-rectal distension. None of the neurones with partial nociceptive convergence recorded (n = 10) ever changed its firing rate during increases of intracolonic pressure up to 100 mmHg. 3. It is concluded that neurones with total nociceptive convergence give monotonic stimulus-response relationships for colo rectal distensions. Thus, neurones with total nociceptive convergence can encode the strength of visceral stimuli, probably within the noxious range, just as they have previously been shown to do for thermal and mechanical cutaneous stimuli. Together with previous electrophysiological and neuroanatomical findings, this study provides further evidence for the convergence of noxious inputs onto single SRD neurones. 4. It is suggested that neurones with total nociceptive convergence could be a link in spino-bulbospinal loops involved in autonomic reactions to strong visceral stimulation. In addition, SRD neurones could be an important supraspinal relay in the mechanisms of visceral pain. PMID- 1302267 TI - Intracellular electrophysiological study of suprachiasmatic nucleus neurons in rodents: inhibitory synaptic mechanisms. AB - 1. The mechanisms responsible for evoked and spontaneous fast inhibitory postsynaptic potentials (IPSPs) in the hypothalamic suprachiasmatic nucleus (SCN) were studied with intracellular recording. SCN neurons, primarily ones identified as receiving excitatory optic nerve input, were recorded in rat and guinea-pig brain slice preparations maintained in vitro. 2. In normal medium, electrical stimulation of a site dorsocaudal to the SCN evoked IPSPs from thirty-three of thirty-six neurons. The evoked IPSPs rose to the peak quickly (8.7 +/- 0.9 ms, mean +/- S.E.M.; n = 15 neurons) and decayed gradually with a time constant of 25 +/- 3 ms. Spontaneous IPSPs were present in each of the thirty-six neurons. These IPSPs had a rise-to-peak time of 7.2 +/- 1.0 ms (n = 6 neurons) and a decay time constant of 14 +/- 5 ms. 3. When recorded with potassium acetate-filled electrodes, the evoked and spontaneous IPSPs were hyperpolarizing at resting membrane potential (less negative than -70 mV) and had a reversal potential of around -75 mV. On the other hand, when recorded with potassium chloride-filled electrodes, the IPSPs were depolarizing at membrane potentials more negative than -50 mV and had an estimated reversal potential less negative than spike threshold. 4. Bath application of bicuculline (10-50 microM), a gamma aminobutyric acidA (GABAA) receptor antagonist, resulted in a complete blockade of both the evoked (n = 16) and spontaneous (n = 13) IPSPs. The bicuculline effects were reversible, and were not associated with any significant and consistent change in baseline membrane potential or input resistance. The neurons impaled in bicuculline-containing medium (n = 11) exhibited neither spontaneous IPSPs nor evoked IPSPs. 5. In some neurons bicuculline-resistant hyperpolarizing potentials, which were similar to the fast IPSPs in time course, occurred spontaneously or were evoked by electrical stimulation of the optic nerve or the dorsocaudal site. A fast prepotential always preceded the hyperpolarizing potential, and hyperpolarizing currents blocked these events, indicating that they were not synaptic in origin. No slow IPSPs were detected. 6. The results suggest that fast IPSPs from non-retinal afferents exist in virtually all SCN neurons receiving excitatory retinal input, and that GABAA receptors associated with Cl- channels mediate the fast IPSPs. PMID- 1302268 TI - Mechanism of release of Ca2+ from intracellular stores in response to ionomycin in oocytes of the frog Xenopus laevis. AB - 1. The mechanism of Ca2+ release from intracellular stores was studied in defolliculated Xenopus laevis oocytes by measuring whole-cell currents using the two-electrode voltage-clamp method. 2. The extracellular application of ionomycin, a selective Ca2+ ionophore, evoked an inward current consisting of a spike-like fast component followed by a long-lasting slow component with few superimposed current oscillations (fluctuations). The ionomycin response occurred in a dose-dependent manner and was dependent on Cl-. 3. No apparent refractory period was observed for repetitively evoked small ionomycin responses when the concentration of ionomycin was low (0.1 microM). In contrast, a larger ionomycin response (1 microM), consisting of fast and slow components, was followed by refractory period. Washing for 50-90 min was necessary for full recovery of the ionomycin response. 4. The response to ionomycin was suppressed by the extracellular application of acetoxymethyl ester of bis-(O-aminophenoxy)-ethane N,N,N',N'-tetraacetic acid (BAPTA AM, 1-10 microM), a membrane-permeable intracellular Ca2+ chelator. 5. The ionomycin response was not affected by pertussis toxin (PTX, 0.3-2.0 microgram/ml), a blocker of guanine nucleotide binding regulatory proteins (G proteins). In contrast, the response to acetylcholine (ACh), which is known to occur via a G protein, was suppressed by PTX. 6. The fast component was not affected by removing Ca2+ from the bathing medium or by replacing extracellular Ca2+ with Ba2+ or Mn2+ (all of these solutions were supplemented with 2 mM EGTA), whereas the slow component was suppressed. 7. Injection of inositol 1,4,5-trisphosphate (IP3) following a response to extra-cellularly applied ionomycin did not evoke an appreciable membrane current. In contrast, ionomycin evoked a small inward current when it was applied after an inward-current response evoked by IP3 injection, whereas a second injection of IP3 did not evoke any appreciable current. 8. The results indicate that (a) ionomycin releases Ca2+ from its intracellular stores without the involvement of G proteins, resulting in activation of Ca(2+)-activated Cl- channels, (b) ionomycin mainly acts on the same intracellular Ca2+ stores as IP3, and (c) entry of Ca2+ from outside the cell considerably contributes to the slow component of the ionomycin response, whereas its fast component is predominantly dependent on the release of Ca2+ from the intracellular stores. PMID- 1302269 TI - Role of bicarbonate in pH recovery from intracellular acidosis in the guinea-pig ventricular myocyte. AB - 1. Intracellular pH (pHi) was recorded ratiometrically in isolated guinea-pig ventricular myocytes using the pH-sensitive fluoroprobe, carboxy-SNARF-1 (carboxy seminaphthorhodafluor). 2. Following an intracellular acid load (10 mM NH4 Cl removal), pHi recovery in HEPES-buffered Tyrode solution was inhibited by 1.5 mM amiloride (Na(+)-H+ antiport blocker). In the presence of amiloride, switching from HEPES buffer to HCO3-/CO2 (pHo of both solutions = 7.4) stimulated a pHi recovery towards more alkaline levels. 3. Amiloride-resistant, HCO(3-)-dependent pHi recovery was inhibited by removal of external Na+ (replaced by N-methyl-D glucamine), whereas removal of external Cl- (replaced by glucuronate, leading to depletion of internal Cl-), removal of external K+, or decreasing external Ca2+ by approximately tenfold had no inhibitory effect. These results suggest that the amiloride-resistant recovery is due to a Na(+)-HCO3- cotransport into the cell. 4. The stilbene derivative DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, 500 microM) slowed Na(+)-HCO(3-)-dependent pHi recovery. 5. Intracellular pH increased in Cl(-)-free solution and this increase still occurred in Na(+) free solution indicating that it is not caused via Na(+)-HCO3- symport and is more likely to be due to Cl- efflux in exchange for HCO3- influx on a sarcolemmal Cl(-)-HCO3- exchanger. The lack of any significant pHi recovery from intracellular acidosis in Na(+)-free solution suggests that this exchanger does not contribute to acid-equivalent extrusion. 6. Possible voltage sensitivity and electrogenicity of the co-transport were examined by using the whole-cell patch clamp technique in combination with SNARF-1 recordings of pHi. Stepping the holding potential from -110 to -40 mV did not affect amiloride-resistant pHi recovery from acidosis. Moreover, following an intracellular acid load, the activation of Na(+)-HCO3- co-influx (by switching from HEPES to HCO3-/CO2 buffer) produced no detectable outward current (outward current would be expected if the coupling of HCO3- with Na+ were > 1.0). 7. Intracellular intrinsic buffering power (beta i) was assessed as a function of pHi (beta i computed from the decrease of pHi following reduction of extracellular NH4 Cl in amiloride containing solution). beta i in the ventricular myocyte increases roughly linearly with a decrease in pHi according the following equation: beta i = 28(pHi) +222.6. 8. Comparison of acid-equivalent efflux via Na(+)-HCO3- symport and Na(+)-H+ antiport showed that, following an intracellular acidosis, the symport accounts for about 40% of total acid efflux, the other 60% being carried by the antiport.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302270 TI - Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons. AB - 1. The effects of diazoxide (DZ) on synaptic transmission and upon responses to exogenously applied glutamate agonists were examined in cultured hippocampal neurons. 2. DZ reversibly increased the peak amplitude of evoked excitatory postsynaptic currents (EPSCs) to 150 +/- 100% of control and prolonged the EPSC decay time constant (tau) from 5.9 +/- 1.2 ms to 14 +/- 6.2 ms (240% of control). 3. Peak and steady-state glutamate (Glu) and quisqualate (QA) currents activated by exogenous application were dramatically increased by DZ at concentrations which did not influence N-methyl-D-aspartate (NMDA), kainate (KA), or GABA currents. These effects were rapidly and completely reversible. Active and passive membrane properties were unaffected by DZ. 4. Inhibitory postsynaptic currents (IPSCs) were unaffected by the same DZ concentrations. 5. These experiments indicate that desensitization plays an important role in terminating excitatory transmission between mammalian central neurons. DZ and perhaps related compounds will ultimately help us identify the regions of the AMPA/KA receptor responsible for desensitization. PMID- 1302271 TI - Three potassium channels in rat posterior pituitary nerve terminals. AB - 1. The patch clamp technique was used to investigate the K+ channels in the membranes of nerve terminals in thin slices prepared from the rat posterior pituitary. 2. Depolarization of the membrane produced a high density of K+ current. With a holding potential of -80 mV, test pulses to +50 mV activated a K+ current which was inactivated by 65% within 200 ms. Hyperpolarizing prepulses enhanced the transient K+ current, with half-maximal enhancement at -87 mV. Depolarizing prepulses reduced or eliminated the transient K+ current. 3. In cell attached patches formed with pipettes containing 130 mM KCl, three types of K+ channel could be distinguished on the basis of single-channel properties. One channel had a conductance of 33 pS and was inactivated with a time constant of 18 ms. A second channel had a conductance of 134 pS and was inactivated with a time constant of 71 ms. A third channel had a conductance of 27 pS, was activated relatively slowly with a time constant of 65 ms, and was not inactivated during test pulses of up to one second in duration. 4. Inactivation of the whole-cell K+ current was a biphasic process with two exponential components. The fast component had a time constant of 22 ms (at +50 mV), corresponding well with the time constant of decay of average current in cell-attached patches containing only the rapidly inactivating K+ channel. The slow component of inactivation had a time constant of 104 ms (at +50 mV), which was similar to but slightly slower than the time constant of decay of the average current in cell-attached patches containing only the slowly inactivating K+ channel. Inactivation of the slow transient K+ current became more rapid with increasing depolarization. 5. The low conductance rapidly inactivating K+ channel had a lower voltage threshold for activation than the other two K+ channels. 6. Both inactivating K+ channels were enhanced in a similar manner by prior hyperpolarization. There was no difference with regard to voltage mid-point or steepness. 7. The large-conductance slowly inactivating K+ channel was activated by Ca2+ at the inner membrane surface. The resting intracellular Ca2+ was sufficiently high to produce significant activation of this channel without depolarization-induced Ca2+ entry. 8. Removal of Ca2+ from the bathing solution produced a -10 mV shift in the voltage dependence of enhancement of both transient K+ currents by prior hyperpolarization. This could be explained as a surface charge effect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302272 TI - Influence of hypertonic-hyperoncotic solution and furosemide on canine hydrostatic pulmonary oedema resorption. AB - 1. This study aimed at enhancing the clearance of experimental hydrostatic pulmonary oedema in dogs using hypertonic-hyperoncotic solution (HHS) and furosemide. 2. Anaesthetized dogs (n = 20) were mechanically ventilated with a positive end-expiratory pressure of 10 cmH2O (1.0 kPa). 3. Hydrostatic pulmonary oedema was induced by inflating a balloon inserted into the left atrium and simultaneously infusing isotonic saline rapidly. Oedema formation was terminated by deflating the balloon and reducing the infusion rate. 4. Four groups were studied: A, control; B, furosemide; C, HHS and D, HHS+furosemide. HHS, 6 ml kg-1, was given as a bolus injection and furosemide, 1 mg kg-1, intravenously as a bolus followed by an infusion of 0.5 mg kg-1 h-1. All dogs were studied for 4 h. 5. Serum osmolarity, plasma colloid oncotic pressure and diuresis in groups C and D (HHS groups) substantially increased; haemoglobin concentration decreased and pulmonary arterial wedge pressure remained constant. 6. Despite the combination of these factors favouring fluid flux from the extravascular to the intravascular compartment, extravascular lung water measured with the double indicator dilution technique decreased no faster in the HHS groups than in the two other groups (from over 26 to approximately 19 ml kg-1 in groups A, C and D and to 14.7 in group B (only furosemide)). 7. This was confirmed by postmortem gravimetric measurements of extravascular lung water; A, 11.0 +/- 5.7; B, 9.7 +/- 3.3; C, 10.5 +/- 3.1 and D, 10.6 +/- 1.8 g kg-1. 8. We speculate that mechanisms other than effective Starling gradients and enhanced diuresis might define a maximal rate of pulmonary oedema clearance. PMID- 1302273 TI - The inward rectifier K+ current underlies oscillatory membrane potential behaviour in bovine pigmented ciliary epithelial cells. AB - 1. Fresh bovine, pigmented ciliary epithelial cells possess an inward rectifier current activated by hyperpolarization. This current was investigated using whole cell patch-clamp techniques. At the holding potential of -70 mV, and with EK (potassium equilibrium potential) set at -84 mV, a small outward current flowed through the inward rectifier that was sensitive to external K+, becoming more outward in 0.5 mM K+ and progressively more inward in 20 and 50 mM K+. 2. The inward rectifier showed V-EK dependence; increasing [K+]o increased the inward conductance from 1.28 nS in 5 mM K+ to 7.42 nS in 50 mM K+. The conductance at a given V-EK was proportional to the square root of [K+]o. 3. It was blocked by external Cs+ but replacing K+ in the pipette with Cs+ blocked only outward ion movement through the inward rectifier. Inward rectification was also blocked by Ba2+ (85% with Ki (concentration giving half-maximal inhibition) = 3.1 x 10(-5) M) and TEA+ (74% with Ki = 2.9 x 10(-4) M). 4. The activation time constant was voltage dependent, decreasing from 5 ms to 0.7 ms over the voltage range -90 to 170 mV. With increasing hyperpolarization the current exhibited time-dependent decay. The time constant for this process was voltage sensitive but the steady state inactivation was independent of external [K+]. 5. The current disappeared in culture within 8 days. 6. Solution flow over the cell inactivated the inward rectifier, a property that may be related to [K+]o. 7. In current clamp the cells exhibited an unstable region at a potential of around -70 mV. Once in this region oscillations and regenerative hyperpolarizing potentials were observed. This behaviour was eliminated by treatments that blocked (Cs+, Ba2+) or removed (0.5 mM K+) active inward rectification. 8. It is suggested that these oscillations may represent a process of cation loading, the first step in the secretion of aqueous humour. PMID- 1302274 TI - Inorganic phosphate decreases the Ca2+ content of the sarcoplasmic reticulum in saponin-treated rat cardiac trabeculae. AB - 1. Measurements of [Ca2+] were made in saponin-permeabilized rat ventricular trabeculae using the fluorescent indicator Indo-1. Application of caffeine (20 mM) caused a transient rise in [Ca2+] within the preparation as a result of Ca2+ release from the sarcoplasmic reticulum (SR). The size of the caffeine-induced Ca2+ transient was related to the amount of Ca2+ accumulated by the SR prior to addition of caffeine. Caffeine-induced Ca2+ release was abolished by ryanodine (10 microM), an inhibitor of SR Ca2+ release. 2. At a bathing [Ca2+] of 0.2 microM, the amount of Ca2+ released from the SR on addition of caffeine was sufficient to generate a tension transient. Ca2+ and tension responses were stabilized by application of caffeine at regular intervals (2 min). Addition of 10 mM inorganic phosphate (Pi) induced a transient increase in [Ca2+] within the preparation due to a net release of Ca2+ from the SR. The amplitude of subsequent caffeine-induced Ca2+ transients were reduced to 65 +/- 7.5% (mean +/- S.D., n = 13) of control. In addition, the accompanying tension transient fell to 45 +/- 6.9% of control. Removal of Pi caused a transient decrease in the [Ca2+] within the preparation consistent with a net increase in Ca2+ uptake by the SR. Subsequent caffeine-induced Ca2+ and tension transients returned to control levels. 3. Inclusion of Pi (2-30 mM) in the perfusing solution decreased the size of caffeine-induced Ca2+ and tension transients in a dose-dependent manner. 4. Addition of 10 mM ADP caused a transient increase in [Ca2+] and depressed subsequent caffeine-induced Ca2+ transients to a greater extent than 10 mM Pi. Despite the reduction in Ca2+ release from the SR, tension responses were larger in the presence of 10 mM ADP than under control conditions. This is a consequence of an increase in Ca(2+)-activated force by ADP. 5. A decrease in the amplitude of caffeine-induced Ca2+ transients also occurred on changing from a solution containing 1 mM ADP and 10 mM Pi to a solution with 10 mM ADP and 1 mM Pi. This confirms the previous observation that ADP is more effective than Pi at reducing caffeine-induced Ca2+ released from the SR. 6. Spontaneous oscillations of [Ca2+] and tension occurred in the presence of 0.5 microM Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302275 TI - Adaptation of quantal content to decreased postsynaptic sensitivity at single endplates in alpha-bungarotoxin-treated rats. AB - 1. Rats were injected once every 48 h with alpha-bungarotoxin (alpha BTX) for periods up to 6 weeks. Injections caused weakness of facial muscles which lasted about 8 h. Hemidiaphragms were dissected for biochemical and electrophysiological measurements. 2. In muscles from animals treated for 2-3 weeks with toxin, the binding of 125I-alpha BTX was reduced to 58%, and the ACh content to 81% of control values. Choline acetyltransferase activity was unchanged. ACh release evoked by 3 Hz nerve stimulation was increased to 175% of control values. 3. The use of mu-conotoxin, which specifically blocks muscle action potentials, enabled the recording of full-sized endplate potentials (EPPs) and miniature endplate potentials (MEPPs) at normal muscle membrane potentials (-70 to -80 mV). The amplitude of MEPPs was decreased to 57% in muscles from animals treated for 3 weeks with alpha BTX. The mean of the quantal contents, calculated from the ratio of the corrected EPPs and the MEPPs, was increased to 154%. 4. Within individual muscles of both alpha BTX-treated and control rats, there was an inverse relationship between the quantal content of an endplate and its MEPP amplitude. 5. The MEPP frequency of endplates from control muscles was positively correlated with the quantal content. However, this correlation was not found in alpha BTX affected muscles. 6. Three hours after a single injection of alpha BTX the amplitude of the MEPPs was reduced to about 60% of control values but no increase of the quantal content was found. During the first few days of alpha BTX treatment the quantal content gradually increased; it reached a plateau between 20 and 30 days. 7. The results suggest the existence of an adaptive mechanism, operating at individual endplates, in which retrograde signals at the motor nerve terminals modulate ACh release when neuromuscular transmission is endangered by block of acetylcholine receptors. PMID- 1302276 TI - Discharge characteristics and rapid resetting of autoactive aortic baroreceptors in rats. AB - 1. An in vitro aortic arch-aortic nerve preparation was used to characterize the pressure-discharge properties of aortic 'autoactive' baroreceptors (aBRs), a functionally unique group of baroreceptors that discharge continuously below pressure threshold (Pth). These units contrast to more familiar 'quiescent' BRs (qBRs) that are silent below Pth. This study also examined whether aBRs rapidly reset to sustained changes in mean arterial pressure (MAP), and whether they respond to local vasoconstriction, as found in qBRs. 2. Pressure-discharge curves were constructed using slow pressure ramps (2 mmHg s-1) in a total of fifty-four aBRs and sixty-four qBRs from fifty-three Wistar-Kyoto rats. Rapid resetting was tested by comparing the curves before and 15 min after adjusting MAP to selected levels between 40 and 180 mmHg. Response curves were also compared before and after constricting the arch with 10(-8) M angiotensin II. 3. Compared to qBRs, aBRs had significantly lower Pth values (83 +/- 2 versus 91 +/- 2 mmHg, mean +/- S.E.M., P < 0.05) but similar threshold frequencies (13 +/- 1 versus 16 +/- 2 Hz), higher saturation pressures (138 +/- 4 versus 123 +/- 2 mmHg) but similar saturation frequencies (55 +/- 3 versus 55 +/- 3 Hz), and lower suprathreshold sensitivities (slope of linear region: 1.1 +/- 0.1 versus 1.4 +/- 0.1 Hz mmHg-1) but wider operating ranges (57 +/- 4 versus 35 +/- 3 mmHg). 4. The aBRs rapidly reset to changes in MAP (n = 16), and the extent of resetting (delta Pth/delta MAP = 0.26) was similar to that in qBRs (0.23). 5. Vasoconstriction had no effect on aBR subthreshold discharge (n = 5), but inhibited suprathreshold responses to pressure much like that in qBRs. 6. These results suggest that aortic aBRs may extend the range of the baroreflex, but probably do not improve its sensitivity to transient fluctuations in pressure or its ability to correct changes in mean pressure over extended periods. 7. Subthreshold discharge in aBRs appears to be an intrinsic property of these units, which was not affected by resetting or changes in vascular tone. At suprathreshold pressures, contraction of local smooth muscle modulates the aBRs and qBRs in a similar fashion by mechanically unloading the sensory endings. PMID- 1302277 TI - Comparison of skeleto-fusimotor innervation in cat peroneus brevis and peroneus tertius muscles. AB - 1. The skeleto-fusimotor or beta innervation was compared in cat peroneus brevis and peroneus tertius muscles, which differ in their composition of fatigue resistant motor units; the slow (S) units predominate in brevis and the fast units (FR) in tertius. 2. In four brevis muscles, of thirty-four beta-axons (from a total of 114 axons supplying extrafusal muscle fibres) twenty-nine were dynamic (beta D) and only five static (beta S). In contrast, in three tertius muscles, of twenty-five beta-axons (from a total of 82 axons) twelve were static and thirteen dynamic. 3. In a population of thirty-five brevis and thirty tertius spindles, the proportion of beta D-innervated spindles was greater in the brevis (68.5%) than in the tertius (50%) whereas that of beta S-innervated spindles was greater in the tertius (40%) than in the brevis (17.1%). In a population of thirty-two brevis and twenty-seven tertius spindles in which the presence of bag1 fibres was deduced from the existence of a dynamic innervation, the proportion of spindles innervated by beta D-axons was 80% in the brevis and 62% in the tertius. 4. In both muscles, the number of beta D effects was greater than that of beta S effects. beta S-axons were rarely found to supply more than one spindle whereas beta D-axons supplying more than one spindle (up to four) were common. Spindles were often coinnervated by beta D- and beta S-axons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302278 TI - A physiological study of vestibular and prepositus hypoglossi neurones projecting to the abducens nucleus in the alert cat. AB - 1. Vestibular and prepositus hypoglossi (PH) neurones projecting to the abducens (ABD) nucleus were recorded in the alert cat. Their discharge characteristics were analysed to ascertain the origin of the horizontal eye position signal present in ABD neurones. 2. Neurones were classified according to: their location with respect to the ABD nucleus; their antidromic activation from the ABD nucleus; the synaptic field potential they induced in the ABD nucleus with the spike-triggered averaging technique; and their activity during spontaneous and vestibularly induced eye movements. 3. Vestibular neurones projecting to the ABD nucleus were located in the rostral medial vestibular nucleus. They were excitatory on the contralateral and inhibitory on the ipsilateral ABD neurones. Both types of premotor vestibular neurone showed a firing rate weakly related to eye position, increasing for eye fixations in the contralateral on-direction, and decreasing with ipsilateral fixation. Position sensitivity during eye fixations was (means +/- S.D.) 1.8 +/- 0.9 spikes s-1 deg-1 for excitatory neurones and 2.2 +/- 1.3 spikes s-1 deg-1 for inhibitory neurones. Firing rate exhibited a high variability during eye fixations. Their responses during saccades in the off direction were characterized by a pause that, although less defined, was occasionally present during saccades in the on-direction. Eye velocity sensitivity during spontaneous saccades in the on-direction was 0.17 +/- 0.15 spikes s-1 deg-1 s-1 for excitatory neurones and 0.15 +/- 0.07 spikes s-1 deg-1 s 1 for inhibitory vestibular neurones. During sinusoidal head stimulation at 0.2 Hz, vestibular neurones showed a type I discharge rate with a phase lead over eye position of 86.0 +/- 14.1 deg for excitatory and 80.2 +/- 12.5 deg for inhibitory neurones. Position sensitivity during vestibular stimulation did not differ significantly from values obtained for spontaneous eye movements. However, the velocity sensitivity of premotor vestibular neurones during head rotation was significantly higher (1.6 +/- 0.2 spikes s-1 deg-1 s-1 for excitatory and 1.5 +/- 0.3 spikes s-1 deg-1 s-1 for inhibitory neurones) than during spontaneous eye movements. 4. PH neurones projecting to the ABD nucleus were located in the rostral one-third of the nucleus. These neurones were excitatory on the ipsilateral and inhibitory on the contralateral ABD nucleus. Their firing rates were correlated mainly with eye position, increasing for abducting eye positions of the ipsilateral eye and decreasing with adduction movements.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302279 TI - Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro. AB - 1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1.1 +/- 0.1 spikes/s (mean +/- S.E.M.). 2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97%) were excited by 10(-6) M AVP with an increase in firing rate from the basal level of 1.1 +/- 0.1 to a maximum of 2.5 +/- 0.2 spikes/s. There was a dose-dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10(-10) M. The remaining six neurones were not affected by application of AVP. 3. Application of oxytocin (OXT, 10(-6) M) increased the firing rate of all thirty-eight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low Ca2+ or Ca(2+)-free-high-Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes. 4. The AVP-induced excitatory responses were completely but reversibly blocked by the V1-type receptor antagonists, [1 (beta-mercapto-beta, beta-cyclopentamethylene-propionic acid), 2-(O methyl)tyrosine]-arginine vasopressin (d(CH2)5Tyr(Me)AVP) (n = 5) and Phaa-D Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly-NH2d(CH2)5[Tyr-(Me)2Thr4]ornithine vasotocin, which suppressed the OXT-induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10(-6) M) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1.0 +/- 0.1 to a maximum of 1.8 +/- 0.2 spikes/s (n = 60). The effect of AII was completely abolished by an AII receptor antagonist, [Sar1,Ile8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on AII concentration in all of eleven neurones tested. The threshold concentration was assumed to be about 10(-9) M. The activity of 5 (3%) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302280 TI - Responses of macaque ganglion cells to movement of chromatic borders. AB - 1. We have measured responses of macaque ganglion cells to moving borders under conditions designed to simulate the minimally distinct border (MDB) task. 2. Extending previous results, we show that minimization of responses of phasic ganglion cells of the magnocellular (MC)-pathway obey the photometric laws of transitivity and additivity. 3. To equal luminance borders, a residual response was present in MC-pathway cells analogous to the second harmonic response seen in these neurones with temporal chromatic modulation. It was proportional to the tritanopic purity difference (magnitude of delta Pt, the rectified middle- to long-wavelength cone opponent signal) between the two colours on either side of the border. For a delta Pt of one, the mean residual response was equivalent to the response evoked by achromatic borders of about 14% luminance contrast. Both these properties of the MC-pathway closely resemble psychophysical estimates as to the distinctness of equal luminance borders. 4. We show how MC-pathway cell responses could be used centrally to support the MDB task. It was difficult to generate a model from responses of tonic ganglion cells of the parvocellular (PC) pathway which would support the task. 5. The MDB task is still possible psychophysically after blurring the retinal image. Although blurring the border spatially smeared the responses of MC-pathway ganglion cells and reduced their amplitude, responses still went through a minimum close to equal luminance. Thus, blurring the image did not affect the ability of MC-pathway cells to support the task. Blurring the retinal image decreased the 'sharpness' of the border response of tonic, PC-pathway ganglion cells, but response amplitude was unaffected. Response features indicative of centre-surround organization were attenuated. A central mechanism reliant on centre-surround field structure of PC-pathway cells would thus not be able to support the task after blurring. 6. Taken together, these results strongly suggest that the MC-pathway forms the sole physiological substrate of the MDB task, and any contribution of the PC-pathway is, indeed, minimal. PMID- 1302281 TI - Depolarizing action of cholecystokinin on rat supraoptic neurones in vitro. AB - 1. Cholecystokinin is co-localized within the oxytocin- and, to a lesser extent, vasopressin-synthesizing magnocellular neurones in the hypothalamic supraoptic and paraventricular nuclei. These nuclei are also prominent binding sites for cholecystokinin. In the present study we used intracellular current- and voltage clamp recordings from fifty-seven supraoptic nucleus cells, maintained in superfused explants of rat hypothalamus, to assess their membrane responses to exogenous cholecystokinin and define the nature of their cholecystokinin receptors. 2. In a majority of the fifty-seven cells tested, bolus infusions into the superfusion media of cholecystokinin fragments (maximum concentrations estimated at 0.3-15 microM) were followed within 1-5 s by a transient and reversible membrane depolarization. Active peptides included sulphated cholecystokinin octapeptide (26-33) (28 of 33 cells responded), non-sulphated cholecystokinin octapeptide (26-33) (21 of 25 cells responded), cholecystokinin tetrapeptide (30-33) (20 of 24 cells responded and caerulein (4 of 4 cells responded). None of five cells responded to cholecystokinin (26-28). Depolarizing responses to cholecystokinin analogues persisted in the presence of tetrodotoxin (0.2-0.4 microM), and in Ca(2+)-free solutions containing MnCl2 (2.5 mM). 3. Under voltage clamp, cholecystokinin fragments evoked an inward current accompanied by an increase in membrane conductance. The amplitude of the inward current varied linearly as a function of membrane voltage, with an extrapolated reversal potential of approximately -15 mV. Reversal potentials were not altered by chloride injection. These features suggest that cholecystokinin activates a non-selective cationic conductance. 4. Active cholecystokinin analogues were approximately equipotent in their depolarizing actions, a feature that supports the activation of cholecystokinin-B type receptors. Moreover bath application of 200 nM L-365,260, an antagonist with a high affinity for cholecystokinin-B receptors, reversibly attenuated the cholecystokinin-induced responses in four of six cells tested. 5. These observations indicate that cholecystokinin can directly influence the excitability of rat supraoptic nucleus neurones and provide evidence for an additional site where this peptide may act within the hypothalamo-neurohypophysial axis. PMID- 1302282 TI - NMDA receptor-mediated rhythmic bursting activity in rat supraoptic nucleus neurones in vitro. AB - 1. Intracellular recordings were obtained from 112 supraoptic nucleus magnocellular neurosecretory cells (MNCs) in superfused explants of rat hypothalamus maintained in vitro. The effects of glutamate receptor agonists and antagonists were examined at 32-34 degrees C. 2. In control solutions, spontaneously active (> 5 Hz) phasic or continuous neurones showed interspike interval distributions slightly skewed toward short intervals, but did not feature pauses in the 0.4-2 s range. Current injection to alter the rate of cell discharge shifted the histograms according to the mean firing rate, but failed to induce intermittent pauses in the 0.4-2 s range. 3. Application of N-methyl-D aspartate (NMDA) induced a mode of firing in which bimodal interspike interval distributions reflected a high incidence of clusters of short interspike intervals (0.5-1.5 s) recurring every 1-3 s. In contrast, firing evoked by application of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid (AMPA) was not associated with a clustering of impulse discharge. 4. The putative endogenous excitatory amino acid transmitters L-glutamate, L-aspartate and quinolinate all mimicked the effects of NMDA. Clustered spiking responses to these agents were reversibly blocked by D,L-2-amino-5-phosphono-valerate (APV), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In contrast, the non-NMDA receptor ligands kainate and quisqualate caused CNQX-sensitive increases in firing rate, but these responses were not associated with the appearance of clustered activity. 5. When applied to cells showing negative resting potentials (< -70 mV), or to neurones hyperpolarized by current injection, responses to NMDA consisted of rhythmic (approximately 1 Hz) voltage oscillations associated with bursts of spike discharge. In the presence of TTX, NMDA could induce subthreshold voltage oscillations in the absence of action potentials. 6. Application of a voltage clamp to potentials between -75 and -55 mV during rhythmic bursting responses failed to reveal any rhythmic oscillation of the membrane current. In all cases, rhythmic bursting activity resumed upon returning to the current-clamp mode. 7. Rhythmic bursting responses to NMDA application were abolished in Mg(2+) free solutions, suggesting that the voltage dependence of NMDA channels served to promote regenerative voltage changes throughout the cycle. The NMDA-induced current itself, however, did not appear to decrease with time, suggesting that a distinct, outward current, was necessary to initiate the repolarizing phase of each cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1302283 TI - Molecular mechanisms in the compartmentalized inflammatory response presenting as meningococcal meningitis or septic shock. PMID- 1302284 TI - Nucleotide sequences and characterization of haemolysin genes from Aeromonas hydrophila and Aeromonas sobria. AB - Extracellular haemolysin is thought to be one of the important virulence factors in Aeromonas infection. Two extracellular haemolysin genes (AHH3 and AHH4) from Aeromonas hydrophila strain 28SA, one (AHH5) from A. hydrophila strain AH-1 and one (ASA1) from Aeromonas sobria strain 33 were cloned into cosmid and plasmid vector DNA in Escherichia coli. The nucleotide sequences of the open reading frames of AHH3 and AHH4 are both 1476 basepairs (bp), whereas AHH5 and ASA1 are 1455 and 1467 bp in length, respectively. The deduced amino acid sequences of AHH3, AHH4, AHH5 and the previously reported aerolysin from A. hydrophila showed a significant degree of sequence homology of over 90% each. The amino acid identity of the ASA1 haemolysin and those from A. hydrophila and Aeromonas trota aerolysins ranged from 58-68%. From DNA hybridization analysis using our cloned haemolysin genes as probes, we found that the AHH5 and ASA1 DNA probes hybridized with about 31 and 75% strains of motile Aeromonas species, respectively. The activity of haemolysins of cloned genes were different in medium agar containing various erythrocytes. PMID- 1302285 TI - Extracellular export of Shiga toxin B-subunit/haemolysin A (C-terminus) fusion protein expressed in Salmonella typhimurium aroA-mutant and stimulation of B subunit specific antibody responses in mice. AB - The Shiga toxin B-subunit has been fused to the 23-kD C-terminus of Escherichia coli haemolysin A (HlyA) and exported from attenuated antigen carrier strain of Salmonella typhimurium aroA (SL3261). The expression of the gene fusion under the control of a synthetic modified beta-lactamase promoter (constitutive expression) and under the iron-regulated aerobactin promoter showed that the fusion protein could be stably expressed and exported out of the bacterial cell in significant amounts so long as high copy number plasmids were not used. Oral and i.p. immunization of mice with the hybrid salmonellae resulted in significant B subunit specific mucosal and serum antibody responses. A comparative analysis of the location of hybrid proteins in the antigen carrier bacterial cell (i.e. cytoplasmic expression and extracellular export) has shown that both modes of expression result in antigen-specific immune responses. This is the first report demonstrating that foreign polypeptides fused to the 23-kD C-terminus of E. coli haemolysin A can be exported from attenuated Salmonella vaccine strains and that such exported polypeptides can result in antigen-specific immune responses. PMID- 1302286 TI - [Differences between patients with right bundle branch block and left anterior hemiblock in Chagas myocardiopathy]. AB - In order to establish whether different kinds of conduction disturbances like complete right branch block (CRBB) and left anterior hemiblock (LAH) are associated with different degrees of myocardial damage in Chagas disease (Chd), we studied 25 patients (p), 15 males and 10 women (41 +/- 5 years old) who were divided into five groups: normal EKG 5 p, incomplete right branch block 5 p, CRBB LAH 5 p. We performed EKG, phonocardiogram, echo-M, 2-D and Doppler. The systolic function was evaluated with velocity of circumferential shortening and Weissler index; parietal motility with score of motility; dilatation with diastolic diameter of left ventricle and diastolic function with isovolumetric relaxation time and E/A ratio mitral and tricuspid. The patients who did not present basal severe arrhythmias were submitted to stress testing. We found that in LAH there were great systolic and diastolic dysfunctions, parietal motility alterations and malignant arrhythmias as compared with CRBB. There was no significant difference between LAH and CRBB-LAH. In Chagas disease, the presence of LAH showed much more myocardial damage than in CRBB. PMID- 1302287 TI - [Cutaneous melanomas in old patients. Prognostic factors and actuarial survival]. AB - A study of 80 consecutive cutaneous malignant melanomas in 78 patients older than 60 years, with an average of 73 (60-93), is presented. The following data were considered: age, sex, localization, stage, other synchronous or metachronous malignant tumors, excluded basal cell epitheliomas, histological type and depth of cutaneous invasion according to Clark's levels and Breslow's measure. The follow up lasted 1 to 156 months with an average of 39 months. All patients were treated by surgical removal of the cutaneous lesion or the regional lymph node metastases, if they appeared. No prophylactic lymph node dissections were performed. There were 45 women and 33 men. The histological type was superficial spreading (ES) in 17 women and 7 men; nodular (NOD) in 18 and 16; lentigo maligna melanoma (LM) in 4 and 4 and acral in 7 and 7. Relations between sex, localization, histological type and actuarial survival curves can be observed in Figs. 5, 6, 7, 8 and Tables 1, 2. Even considering the shortcomings of this retrospective analysis and a relatively short follow up for melanomas, this study points out that the thickness of the lesion became prognostically significant in relation to survival, beyond 3.7 mm (p < 0.001); but when the tumors were thinner, this group of patients showed other causes of death (MPOC) with a greater frequency than those related to tumoral progression (MPM) (p < 0.001) and that maybe this should be taken into account when planning treatment for melanomas in elderly patients. Other malignant synchronous or metachronous tumors were found in 19% of the patients (Table 2). PMID- 1302288 TI - [HIV-1 infection in patients with hemophilia. The Argentinian experience from 1983 to 1990]. AB - We present studies on the evolution of HIV-1 infection in 638 hemophilic patients receiving commercial antihemophilic concentrates (CAH) at the Institute of Hematological Research and the Argentine Foundation of Hemophilia between 1983 and 1990. Positive serology for HIV-1 was detected in 30% of the patients studied. Prevalence of HIV-1 infection was higher (about 70%) in the group with severe hemophilia requiring more CAH, but there were no differences between patients with hemophilia A or B. Sexual transmission was demonstrated in 8/64 women (13%) with stable sexual relationship with HIV-1 + hemophilic patients. Three of them became pregnant, and HIV-1 infection was demonstrated in two of the three children. In general, the clinical evolution, as well as the hematologic and immunologic parameters of infected patients were similar to those described for the hemophilic population in other occidental countries. Opportunistic infections were also those observed elsewhere (with predominance of P. carinii pneumonia and disseminated Candida infections). However, the presence of fatal chagasic encephalitis in two of the patients with AIDS is unusual. Thus, central nervous system localization of T. cruzi (which can be observed during the acute period of T. cruzi infection or in immunosuppressed patients), must be considered as a possible severe complication of HIV-1 disease in T. cruzi infected patients. PMID- 1302289 TI - [3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency as a cause of severe neurological damage]. AB - This paper describes the first Argentine case of 3-hydroxy-3-methylglutaric aciduria, a genetic defect of ketogenesis and leucine catabolism step. At the age of 4 months, the patient presented a life-threatening episode of hypoglucemia, metabolic acidosis and hyperammonemia resembling Reye syndrome. The lack of urinary ketone bodies, normal levels of plasma aminoacids and normal urinary excretion of p-hydroxyphenolic acids, led us to look for a ketogenic defect. An abnormal profile of urinary organic acids detected by thin layer chromatography and later characterized and quantified by gas chromatography-mass spectrometry (Figs. 1, 2; Table 1), showed a marked increase in the acidic metabolites typical of the 3-hydroxy-3-methylglutaric aciduria: 3-hydroxy-3-methylglutaric, 3 methylglutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids. The activity of 3-hydroxy-3-methylglutaryl coenzyme A lyase was absent in white cell pellets and between 2-5% of the control values in skin fibroblasts (Table 2). Treatment of the disorder, mainly restricted leucine or low-protein diet and addition of L carnitine had no significant effect on the severe neurological injuries present since the first illness. MRI of the brain, at the age of 1 year and 8 months, showed images in T1 suggestive of marked cerebral atrophy and in T2 hyperintensive images predominating in the right frontal and posterior parietal areas and of the punctiform lesions in the basal ganglia, particularly in the heads of both caudate nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302290 TI - Serum osteocalcin in normal menstrual cycle. AB - Serum osteocalcin (OC) was serially measured along an ovulatory menstrual cycle in 4 healthy unmedicated volunteers (age 33-38 years). During the study the women maintained their normal diet and daily physical activity. Starting at days 4-5 of the cycle, blood samples were taken between 09-11 AM every 2 or 3 days for OC, FSH, LH, E2 and P determinations. Daily ultrasound assessment of ovulation was performed in all subjects between days 7-18 of the cycle. Hormone determinations and OC were performed by RIA. While blood levels of FSH, LH, E2 and P changed during the cycle, according to the expected ovulatory pattern, serum OC concentrations remained stable during the cycle in each subject. In conclusion, serum OC is independent of the gonadotropin and ovarian steroid variations during the normal menstrual cycle. PMID- 1302291 TI - Protein restriction and progression of chronic renal failure. AB - The effect of protein restriction upon the rate of renal functional decline was studied in 7 patients with moderate chronic renal failure (CRF). The rate of progression of CRF was evaluated by the reciprocal of plasma creatinine concentration (1/Cr) in time method, every 1-3 months, during 12 months while on ad-libitum diet and 23-40 months thereafter while on protein restriction. While on ad-libitum diet, 4/7 patients showed a progressive disease and the other 3 showed a relatively stable evolution. Six months after protein restriction, patients with a previous progressive disease showed an amelioration in the decline in renal function, and those with stable CRF showed a worsening of the disease in two cases and an improvement in the other one. During the first six months on low protein diet, a transitory increase in plasma creatinine concentration was observed, being maximum at 2.7 months. Plasma urea concentration fell, after protein restriction, to values close to that predicted at the time of the prescription of the diet. Mean systolic and diastolic arterial blood pressure remained stable throughout the study and it was not necessary to change the pharmacological treatment. Our data show that protein restriction decreases the rate of progression of CRF in patients with previous progressive disease. This benefit may result from the suppression of compensatory hyperfiltration induced by low protein diet, as suggested by the increase in plasma creatinine concentration. PMID- 1302292 TI - [Diagnostic and prognostic elements of echography in parapneumonic pleural effusion]. AB - A retrospective study was made with the purpose of testing Ultrasound usefulness in differential diagnosis between empyematous and non empyematous evolution of parapneumonic effusions. A total of 64 patients with pneumonia and pleural effusion assisted between February 1st, 1982 and June 30th, 1989 had an Ultrasound transparietal study at the beginning and after 3 and/or 7 days of admission, with a real time equipment and a 3.5 Mhz linear transducer; they ranged between 12 and 90 years old, 27 were females and 37 males. Of these, 51 were cured by medical treatment, and 13 needed surgical drainage because of empyema evolution. The very high significant statistic signs of good prognosis in Ultrasound study were: free effusion (Table 2, p < 0.0002), maximal width less than 30 mm in sitting position (Table 1, p < 0.0001), unblurred peripleural images (Table 3, p < 0.002), and maximal homolateral diaphragmatic movement percentage more than 39% of the total (Table 4, p < 0.004); in the evolution, decrease of the maximal width effusion and slow improvement of diaphragmatic movement. Patients not included in the previous setting (31.2% of the total) were in the risk group (Fig. 1) and had loculated effusion, and/or maximal width of 30 mm or more, and/or blurred peripleural images, and/or homolateral maximal diaphragmatic movement percentage lower than 25% of the total. Less than half of this risk group was cured only with medical treatment; and they had an ultrasound evolution similar to the others cured in the same manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302293 TI - [Chronic hexosaminidase A deficiency associated with pure sensory peripheral neuropathy]. AB - One patient with hexosaminidase A (Hx A) deficiency, which produces GM2 gangliosidosis, developed a complex progressive neurological syndrome, starting when he was 10 years old, which encompassed intellectual impairment, cerebellar involvement, features of upper and lower motoneurones compromise and sensory neuropathy without signs of motor fibre damage within the peripheral nerves. Sural nerve biopsy demonstrated loss of myelinated fibres, mainly of those of large and small diameters, clusters of small diameter fibres, fibres with abnormal thin myelin sheaths related to their axonal diameters, axonal degeneration, segmental and paranodal demyelination and remyelination. Electronmicroscopic examination showed small electrondense, non specific, bodies and concentric lamellar inclusions within the cytoplasm of the Schwann cells. These findings demonstrate that pure sensory peripheral neuropathy should be considered as part of the spectrum which may result from Hx A deficiency. PMID- 1302294 TI - [Elevation of ST segment and Bezold Jarisch reflex as evidence of early post thrombolysis reperfusion]. AB - The prognosis of patients with acute myocardial infarction (AMI) depends on the patency of the infarct-related coronary artery. This is the reason why the early recognition of the result of thrombolysis is very important in order to implement more aggressive studies and more complex treatments in case of failure. A clinical syndrome of "early coronary reperfusion" with an excellent correlation with angiographic data has been identified, characterized by: 1) pain decrease in more than 50%, 2) descent of ST segment elevation of more than 50%, 3) early elevation of creatinine phosphokinase (CPK) enzyme; other signs of reperfusion described are the Bezold Jarisch reflex (bradycardia and arterial hypotension) in patients with inferior AMI, an additional elevation of ST segment during thrombolytic infusion. These two signs of successful thrombolysis were seen early and together in our patient. He was a 41 year old male who had an anterior AMI 4 months before admission to our Coronary Care Unit with diagnosis of unstable angina (rest angina). After 10 hours he began with intensive precordial pain of 30 minutes with 2 mm of ST segment elevation in inferior leads. Streptokinase (STK) (1,500,000 units) by infusion was administered during 45 minutes; at 30 minutes of infusion the patient had an increase of ST segment elevation in the same leads which reached 3 mm and decreased to basal line after 2 hours. He also had bradycardia and hypotension which improved with atropine 1 mg IV. An episode of acute heart failure (confirmed by clinical, radiological and hemodynamic data) resolved just before the end of STK infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302295 TI - [Myelodysplasia, hemolysis, and infections]. PMID- 1302296 TI - [Hyperlipidemia and cardiovascular diseases]. PMID- 1302297 TI - [Growth disorders. Critical evaluation of diagnostic methods]. PMID- 1302298 TI - [50 years of Crush syndrome]. PMID- 1302299 TI - Comparative evolution of mipafox-induced delayed neuropathy in rats and hens. AB - Adult male Long-Evans rats and White Leghorn hens were given 30 mg/kg mipafox ip. Administration of this organophosphorus ester resulted in > or = 89% inhibition of brain and spinal cord neurotoxic esterase activity in both species 4 hr after dosing. Our sequential, comparative study of the bilateral mipafox-induced neuropathy in the medulla and cervical spinal cord in hens and rats demonstrated that the rats had well-developed, vacuolar axonopathic lesions in the fasciculus gracilis by post-dosing day 7. Severely affected rats with such lesions were noted through day 21, but not subsequently (days 28 and 35). The hen had a slower developing, but more severe, consistent and longer lasting neuropathy than the rat. In these birds, lesions in the medulla and rostral cervical spinal cord levels were more extensive, involving large regions of both the spinocerebellar tracts and fasciculus gracilis. Neuropathic changes, including myelinated fiber axonopathy and Wallerian-like degeneration, were prominent from days 14 - 35 in hens, and were associated with prominent gliosis in the later stages. PMID- 1302300 TI - Brain aluminum in Alzheimer's disease using an improved GFAAS method. AB - Aluminum (Al) has been determined in autopsy brain samples (20 mg, dry weight) from 10 histologically verified Alzheimer's disease (AD) patients and 10 neurologically normal controls using an improved graphite furnace atomic absorption method. The method makes use of a potassium dichromate matrix modifier to circumvent interferences to the Al determination by the high levels of phosphorus and alkali metals in brain tissue. Brain regions studied included middle frontal gyrus, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri. Small, but significant (p < 0.05) elevations of Al were observed in AD hippocampus, inferior parietal lobule and superior and middle temporal gyri, compared to corresponding control tissues. In contrast to other reports in the literature, no extremely high Al levels (> 20 micrograms/g, dry weight) were observed in our samples. Our highest value for Al in AD brain was 8.0 micrograms/g. These results suggest that there is a small focal increase of Al in specific regions of AD brain compared to age-matched controls. The fact that the increase is small, coupled with the analytical difficulties of accurate bulk sample Al determinations by any technique in the brain matrix, may account for the discordant literature reports for Al in AD brain. PMID- 1302301 TI - Comparative dose-response studies of organophosphorus ester-induced delayed neuropathy in rats and hens administered mipafox. AB - A single injection of mipafox was administered to both Long-Evans hooded rats and White Leghorn hens in dosages which inhibited the activity of brain neurotoxic esterase 30-50%, 60-80%, or greater than 80% four hr after intoxication. All animals were monitored for clinical evidence of organophosphorus induced delayed neuropathy for 21 days, euthanatized, and regions of the nervous system were histologically evaluated. Only hens manifested clinical signs of neuropathy; however, light and electron microscopic lesions were present in the nervous systems of both species. In rats, these lesions were well developed in only the highest dosage group and confined to the rostral level of the fasciculus gracilis in the medulla oblongata. Swollen axons containing a single vacuole filled with flocculent material were the most prominent lesion in rats. Hens manifested more extensive and varied fiber breakdown in multiple spinal cord tracts, with the intensity of degeneration increasing with increasing dosages of mipafox. Both marked Wallerian-like degeneration and swollen axons filled with aggregates of cellular debris were observed in the nervous systems of hens. This study indicates that both rats and hens are susceptible to OPIDN. However, there are qualitative and quantitative differences in both clinical manifestations and histologic appearances between the two species. PMID- 1302302 TI - Lead exposure during different developmental periods produces different effects on FI performance in monkeys tested as juveniles and adults. AB - Monkeys (Macaca fascicularis) were dosed with 0 or 1500 micrograms/kg/day of lead as lead acetate according to one of four regimens: Group 1, vehicle continuously from birth; Group 2, lead continuously from birth; Group 3, lead from birth to 400 days of age and vehicle thereafter; Group 4, vehicle from birth to 300 days of age and lead thereafter. Blood lead values of the three treated groups were approximately 20-35 micrograms/dl, depending on age. Performance on a multiple fixed interval-fixed ratio (mult FI-FR) schedule of reinforcement was assessed when monkeys were three years of age, and again at 7-8 years of age following exposure to other behavioral tasks. Results of the first assessment were largely negative, with lead-treated monkeys failing to exhibit the rate increases on the FI observed in previous groups of monkeys tested at the same age. The second assessment revealed increased run rates and decreased average IRTs on the FI in all three treated groups. Effects on the FR component were minimal and transient during both assessment periods, which is consistent with previous results. Monkeys in previous studies had a history of tasks with trials procedures, in which every correct response was reinforced, before being tested on the mult FI FR. The monkeys in the present study had no such history before the first assessment, but extensive exposure to trials procedures between the first and second assessment. It may be that the negative results of the first assessment and positive results of the second are the result of an interaction of lead with such a behavioral history. This suggestion is especially compelling in view of the results from Group 3, dosed only during infancy. These monkeys were unaffected during the first assessment, performed two years after cessation of dosing, but performed differently from controls on the second assessment, performed 5-6 years after cessation of dosing. This finding, combined with data from previous experiments, suggests that the greater total dose of lead accumulated by Groups 2 and 4 between the first and second assessment is not an explanation for the difference in results. These results also indicate that exposure to lead during infancy is not necessary for FI performance to be affected, and that exposure only during infancy is sufficient to produce effects. PMID- 1302303 TI - Bone and calcium homeostasis. AB - The principal repository of calcium is bone. Calcium enters bone largely via the trabeculae, with the rate of calcium clearance by bone approximating 50 percent. Calcium enters bone as an ion in solution, but undergoes a phase change to a solid as soon as in contact with the bone surfaces. Calcium removal from and redistribution in bone is mediated by the bone cells, principally osteoblasts and osteoclasts. Calcium enters the body via intestinal absorption, a transport process that is the vectorial result of a saturable and an non-saturable step. Calcium leaves the body in the urine and stool, with a circulating calcium ion having one chance in about four of being lost via excretion. Ions like lead can compete with calcium at the sites of calcium deposition and transport. Their rate in the body should therefore parallel that of calcium, but may be modified by differing binding affinities or interactions with specific sites and molecules. PMID- 1302304 TI - Osteoblasts and chondrocytes are important target cells for the toxic effects of lead. AB - The skeleton is a major repository for divalent cations, including toxic heavy metals such as lead. Unfortunately the effects of such agents on bone (and cartilage) have been minimally investigated in the past. With the current level of understanding of the mechanisms of bone formation and cartilage development it is now appropriate to begin to research the effects of lead on cellular processes. The following discussion describes some of the points of regulation in bone and cartilage formation where interference in metabolic processes could compromise the development of normal tissues as well as affect the homeostatic mechanisms of the skeleton. PMID- 1302305 TI - Modeling bone mineral metabolism, with special reference to calcium and lead. AB - Realistic modeling of lead kinetics requires both qualitative and quantitative understanding of bone metabolism. In this paper, bone metabolism is discussed based on the behavior of Ca, Sr, and Ra tracers. Apposition, the increase of mineral volume, is the chief feature of bone metabolism in the neonatal and young animal. Resorption, which together with apposition functions to model the growing skeleton, is also important during growth. In adulthood, with stabilization of the total bone mass, resorption balances apposition at a relatively low level. This continuing low-level resorption/apposition remodeling process maintains healthy bone and restructures the bone in response to changing functional demands. In addition to these processes, surface exchange and diffuse exchange occur in bone. Rapid exchange between blood and bone calcium (or tracer) takes place at all bone surfaces in intimate contact with blood. Diffuse exchange is a slow process by which bone-seeking elements can penetrate the entire bone volume. Particularly in longer-lived animals like humans, slow exchange of tracer with bone Ca is the dominant mechanism of tracer uptake during adulthood. These three mechanisms of uptake and loss (apposition/resorption, rapid exchange, and diffuse exchange) appear to be the essential mechanisms determining metabolism of bone seeking elements. The magnitudes of accretion plus rapid exchange, of resorption, and of diffuse exchange have been estimated with the aid of radiotracers and fluorescent markers. PMID- 1302306 TI - Intestinal interactions of lead and calcium. AB - The biological interactions between lead and calcium are complex and not well understood, but can be demonstrated in virtually every tissue. High affinity lead binding to intracellular calcium receptor and transport proteins as well as the involvement of lead in calcium-activated and calcium-regulating processes may provide a molecular basis for the broad spectrum cellular and systemic effects. The intestinal absorptive cells are responsible for transporting the entire body complement of calcium and most of the body lead burden. They represent, therefore, the first critical step in maintaining systemic and cellular calcium homeostasis, as well as the first line of defense against lead poisoning. Any interactions which occur at this level, either to enhance the body burden of lead or to diminish the transport of calcium, may have serious health-related repercussions. This article reviews research concerning those interactions involving calcium, lead and the vitamin D endocrine system which ultimately influence intestinal function, calcium homeostasis and body lead retention. PMID- 1302307 TI - Selected aspects of the spatial distribution of lead in bone. AB - The macrodistribution of lead within the skeletal system is not uniform, and is clearly dependent on bone type (compact or trabecular), age and (to a lesser extent) gender. During active growth, lead deposition favors trabecular bones sites but in adulthood lead accumulates more actively in compact bone. The extent and patterns of the higher variability in trabecular bone sites require better definition through further study. Lead tends to be deposited in bone at sites of most active calcification at the time it is absorbed. During the first 15 years of life the bone growth centers dominate the process of calcification. In adulthood osteon remodelling and trabecular plate mineral exchanges are the principal calcifying sites. Both patterns probably deteriorate in old age. Microdeposition patterns of lead could be expected to conform to these changes. However, it is difficult to integrate the reported information into a clearly defined chronological sequence, because many of the studies did not control for age and other variables with sufficient precision. Furthermore, kinetic studies suggest lead is deposited in multiple sites not only among soft tissues but also within bone in molecular forms possessing varying affinities. Current efforts to design instrumentation for in vivo diagnostic lead measurements as well as therapeutic methods to mobilize and remove lead in bone require more precise knowledge than is now available concerning lead macrodistribution, microdistribution and anatomic sites of kinetic compartments. Appropriately designed studies employing contemporary, sensitive techniques involving isotopes, microradiographs, autoradiographs, histology, tomography, and high energy x-ray fluorescence (synchrotron radiation-induced x-ray emission-SRIXE) are now capable of generating the needed data. PMID- 1302308 TI - Sampling of cortical and trabecular bone for lead analysis: method development in a study of lead mobilization during pregnancy. AB - The paper describes a methodological approach to the investigation of maternal fetal transfer of lead in a non-human primate species, with particular focus on skeletal tissue, which is known to be a site of lead deposition. Eight female cynomolgus monkeys were dosed with lead acetate during gestation, and in four of the animals, the isotopic composition of the lead was modified by enriching the amount of the stable isotope 204Pb included in the dose. Biopsy and dissection procedures for the preparation of bone samples for lead analysis and stable lead isotope analysis are described. Emphasis is placed on the containment of potential contamination of the samples by lead during preparation. Containment procedures included: use of a Class 100 clean room, special cleaning regimes and use of Teflon containers and stainless steel instruments. Preliminary data of lead concentrations in adult bone (trabecular and cortical) and fetal bone subsequent to the dosing regimen of lead during pregnancy, suggest notable differences between the two bone "compartments" examined. The bone samples of fetuses from the dams which had received enriched 204Pb showed drastically reduced 206Pb/204Pb isotope ratios. PMID- 1302309 TI - Microdistribution of lead in bone: a new approach. AB - A knowledge of the microdistribution of lead in bone is important in order to understand the mechanisms for accumulation and release of lead. The availability of the synchrotron x-ray microscope for sensitive measurements of bone content and distribution of lead provides a valuable tool which, when combined with kinetic, balance, and tissue measurements, can lead to better evaluation of lead toxicity. It may also provide the basis for the development of a suitable model of how lead behaves in the human body. An outline of an experimental protocol for exploitation of the x-ray microscope is given, along with synchrotron x-ray microscope measurements of the distribution of gallium in rat bone that demonstrate the feasibility of the experimental approach. PMID- 1302310 TI - Removing lead from bone: clinical implications of bone lead stores. AB - The chelating agent, CaNa2EDTA, has proven useful for both the diagnosis and treatment of lead poisoning. The EDTA lead-mobilization test has demonstrated the presence of excessive body lead stores when blood concentrations were "normal." The EDTA lead-mobilization test is, however, impractical because it requires injections and timed urine collections. Bone lead measured in biopsy specimens by atomic absorption spectroscopy shows a good correlation with chelatable lead. Over 95% of the body stores of lead are retained in bone with a biological half life approximating two decades. The half-life of lead in blood, on the other hand, approximates one month. Bone, therefore, provides a good estimate of cumulative lead absorption. In vivo tibial K x-ray fluorescence (XRF) is a safe, specific and reliable technique for the non-invasive measurement of elevated bone lead concentrations. K XRF measures lead to a depth of about 2 cm in cortical bone and is largely independent of geometric factors because lead is measured relative to bone calcium. In vivo tibial K XRF can therefore replace the EDTA lead-mobilization test and bone biopsies for assessing body lead stores and for following the efficacy and endpoint of deleading during chelation therapy. PMID- 1302311 TI - [Inter-related arterial and venous pathologies]. AB - The authors concomitant arterial and venous disorders. On the same patient. They point out the obvious preeminence of arterial disease on venous ones, and discuss about the panel of therapy association usable. They underline the necessity of saving the venous capital. PMID- 1302312 TI - [Pulmonary endarteritis. A rare complication of sclerotherapy of varices]. PMID- 1302313 TI - [The value of functional studies in superficial venous insufficiency]. PMID- 1302314 TI - [Evaluation of the results of the curative treatment of varices using 3 scoring systems: clinical, Doppler and echographic]. AB - There have been many studies reporting results of curative treatment of varicose veins. Four methodological errors are nevertheless often committed: groups of varicose vein patients not comparable with regard to the degree of venous dilatation; insufficient objective parameters; population inadequately followed up; retrospective studies. It was felt necessary to develop systems for the quantification of varicose disease. These systems provide three grades: a clinical grade, a Doppler grade and an ultrasonographic grade. Clinical grade essentially involves the maximum diameter of varicose veins found by palpation and expressed in millimetres. The Doppler grade takes into account the maximum duration of the reflux wave in compression-decompression manoeuvres. The ultrasonographic grade also involves the maximum diameter of the varicose system. These grades enable the numerical assessment of the results of curative treatment of varicose veins, as well as forming the basis for statistically satisfactory epidemiological surveys. PMID- 1302315 TI - [The treatment of microvarices, varicosities and telangiectasis in 1992]. PMID- 1302316 TI - [The role of the European Community in matters of health care]. PMID- 1302317 TI - [Socioeconomic impact of venous diseases in Italy]. AB - The data's from National Statistic Institute referring to all Italians hospitalized during 1988 are: 37,312 patient due venous diseases, 2.03 p. cent of all hospitalized patients. Varicose veins diseases are more represented in female (10,948 f. and 4,476 m.). A regional study shows an increase in the north of Italy. The medium amount of days in hospital per patient is reduced in the last years at 11 day (from 18 d). The days in hospital in phlebophatic patients were 409,568 (20,522,122 d. for all diseases) during 1988. The expenses for hospital charges due to venous diseases were estimated in 163,827,000,000 of Italian liras, 136,522,500 US. dollar. Other report consider the factory working as the most important in the scale of job inducing phlebophaties. The first seems to be textile industries, at the second place the food factory, the last are builders. In 1974 were lost 2,300,000 working days. We suppose that increasing of private angiological assistance and having a poor public assistance in Italy the patients undergone to hospitals are reducing (81,599 with venous diseases in 1974 and 37,312 in 1988). PMID- 1302318 TI - [The socioeconomic impact of venous pathology in Great Britain]. AB - The chief venous diseases which may have notable or costly economic consequences are, on the one hand, varicose veins and phlebitis (superficial and deep) with their sequelae of chronic venous insufficiency and of ulcers, and, on the other hand, pulmonary embolism and its prevention. The incidence of the former is higher and treatment is very costly. The cost of leg ulcers only in Britain is estimated at 600 million pounds per year. Pulmonary emboli have notable economic consequence because of the cost of preventive and essential measures against such events, which are often fatal. PMID- 1302319 TI - [The importance of chronic venous insufficiency. Various preliminary data on its medico-social consequences]. AB - The study is based on the data's of general practitioners of some Health Communities in Portugal in 1991. On 4,247 patients 1.5 p. cent consulted for venous disease, half of them with severe chronic venous insufficiency. The patients with ulcers needed an average of 32 dressings. Mean disability lasted 38.7 days and 12.5 of the patients took early retirement. The social cost of the disease is set out in this study. The author concludes that prophylactic measures should be taken at the working place. PMID- 1302320 TI - [Various aspects of phlebology in Sweden]. AB - The incidence of symptomatic varicose veins seems to be about the same in most industrialized countries. After decades of radical surgical treatment of most cases with this condition a much more restrictive attitude seems to be present. Patients with limited varicose veins are often told that since there is no medical danger suffering from simple varicose veins, surgery is not necessary. A simple compression stocking is frequently advised. For those patients suffering from symptoms or a finding that their varicose veins are cosmetically disturbing, surgery is performed, however, restricted to be as minor as possible. The long saphenous vein is saved in those parts being competent. The surgical procedures are performed on an outpatient basis in almost all cases which means that the cost has been very much decreased. The incidence of venous leg ulcers has also decreased in Sweden. We seem to have an incidence of 0.3 p. cent ulcers of which 54 p. cent are of venous etiology. The cost for treatment of these patients is here as everywhere else very high as is also the cost for sick-leave. A conservative attitude using compressing stockings and screening to find out in which cases reconstructive venous surgery might be a possibility seems advisable especially in recurrent ulcer cases. PMID- 1302321 TI - [Socioeconomic aspects of phlebologic disorders in the Benelux countries. European standardization of pressure therapy using the compression stocking]. PMID- 1302322 TI - Measuring units for elastic stockings: priority to mmHg rather than classes. AB - Seven incontrovertible arguments show that the only valid measurement unit for elastic stockings is the millimetre of mercury and not a grading system. The mmHg is an international measurement unit; a new European grading system will make prescribing much more difficult; the degree of arterial insufficiency is calculated by taking systolic pressures by Doppler and is expressed in mmHg; in case of superimposition of elastic stocking, pressure add together but not grades; the unit used for pressure instruments is the mmHg; a clinical situation may require a compression force straddled between two grades; finally, new materials will certainly provide increasingly precise forces. PMID- 1302323 TI - [The blue rubber bleb nevus or the cellular blue nevus or Bean syndrome. A rare case of iron-deficiency anemia]. AB - Described by Bean in 1958 the Blue rubber bleb nevus syndrome is a viscero cutaneous hemangiomatosis, a rare condition associating typical cutaneous and visceral hemangiomas of the cavernous type. We report the case of a four year old boy who presented a microcytic and hyperchromic anemia. The previous medical history of this boy was characterized by a large cavernous angioma on the right hand operated on the at the age of three months. The stools were guaiac-positive; examination of the gastrointestinal tract to clarify the etiology of gastrointestinal bleeding was negative. An oral iron therapy was prescribed for several years by the pediatrician. At age nine and half years Labeled erythrocytes demonstrated that gastrointestinal bleeding still continues. The indication for surgical operation was established: Small bowel enteroclysis revealed an oval filling defect in the lumen of ileum. Intraoperative finding: Protuberous hemangioma in the wall of small bowel; resection of the involved intestine and primary anastomosis were performed. On histological examination a cavernous hemangioma has been observed. Clinic and Pathology of this rare condition are discussed. PMID- 1302324 TI - [Low flow venous malformations in children]. AB - Low flow venous malformations in children are a diagnostic and therapeutic challenge. They are present at birth but may not be evident; they have a commensurate growth. They are pure or combined (capillary or lymphatic-venous). At examination, one observed soft, compressible bluish swellings; there is no thrill or bruit. They are slow flow anomalies with venous stasis which may induce thrombosis or localized consumptive coagulopathy. Skeletal distortion or bony hypertrophy or hypoplasia may also be observed; histological examination of surgical specimen reveals infiltration of adjacent structures (skin, bone, muscle); ultrasonography and duplex-Doppler may be helpful in differentiating the venous malformation from lymphatic or arteriovenous anomalies. Diagnosis from hemangioma will be obtained by magnetic resonance imaging; this last investigation will also provide informations on the infiltration of the adjacent tissues by the pathologic process. Standard X ray may show phleboliths of skeletal distortion. Most of venous malformations are asymptomatic and treatment consists in reassuring the child and in giving advice to the parents to prevent trauma to the lesion. Conservative treatment must be advocated (compression garments, prevention of thrombosis with salicylates) since total excision of venous malformation is illusory and postoperative morbidity may be important. Surgical excision of limited cumbersome malformations may be indicated; sclerotherapy of the lesion with Ethibloc makes surgery easier. PMID- 1302325 TI - [Cutis marmorata telangiectatica congenita. Apropos of 4 new cases]. AB - Cutis Marmorata Phlebectasica is a rare congenital disorder characterized by persistent erythrocyanotic mottled areas associated with superficial phlebectases with cutaneous atrophy and ulcerations. The anomaly is present at birth. Spontaneous improvement is the rule. Four cases are described with vascular investigations, coloured echo-Doppler and phlebography. The deep venous tracts are shown to be dilated. Reflux is shown to the superficial veins. PMID- 1302326 TI - [An epidemiologic study of the pathogenesis of varices. The Bochum study I-III]. AB - A longitudinal study was carried out at 11 secondary schools (Gymnasium) of the city of Bochum to investigate the early and preclinical stages of developing varicose veins. The same pupils were examined when being in the 5th, 9th, and 13th classes (Bochum Study I, II and III). A significant correlation between familial predisposition and the occurrence of varicose veins could not be found until the Bochum Study III. The girls dominated with respect to reticular varices and telangiectasias, the boys with respect to trunk varices, branch varices and incompetent perforators. Photoplethysmography showed shorter refilling times for children and adolescents than for adults, but was not suitable to distinguish between pathological and normal findings. Large varices appeared later than small varices and were preceded by refluxes of the long and short saphenous veins. We thus have for the first time a preclinical sign, which clearly identifies individuals at risk. PMID- 1302327 TI - [The 1st clinical signs of venous insufficiency in children]. PMID- 1302328 TI - [Sclerotherapy in children]. AB - The treatment of superficial venous pathology of child is still not very developed. Yet, the frequency is certainly above the estimation of 2% made in 1969. The importance of its expansion should leads us to consider a precocious treatment. Every delay might be the source of difficulties in the future therapeutics. The preliminary non prospective study realized here, includes 43 young patients, whose mothers had varicose. The functional investigations were made after a clinical examination evocative of anomaly and they permit to evidence 6 significant reflux. The therapeutic attitude depended on the type of disease observed going from abstention till surgery. A soft sclerotherapy, generally well accepted, was a successful method without complications. The results difficult to evaluate except in case of reflux, were generally good. The main difficulty is the acceptance of this method by the medical staff, after the parents' agreement. The sclerotherapy is perfectly possible in childhood, often to be wished in case of disease, sometimes necessary, but must remain careful. PMID- 1302329 TI - [Leukocyte entrapment in chronic venous stasis: myth or reality?]. PMID- 1302330 TI - [Anatomo-clinical considerations in microvarices]. PMID- 1302331 TI - [A comparative study of the hydrocellular dressing Allevyn and the hydrocolloid dressing Duoderm in the local treatment of leg ulcers]. PMID- 1302332 TI - [Syntonic phenomena, autism and proportion]. AB - The authors on the basis of extensive literature discuss the phenomenon of syntonia, autism and proportion in schizophrenia. Referring to their own research on the formation of different types of proportion, the authors define the understanding of syntonia and autism. PMID- 1302333 TI - [Gender differences in schizophrenia]. AB - The authors conclude that most male schizophrenic patients display poorer premorbid functioning during the early stages of the illness. They more often display structural micro-abnormalities of the brain, organic deficits, are more chronic and have poor prognosis. Female patients are more often burdened with genetic factors, more often express productive and affective symptomatology, are more sensitive to neuroleptics and the course of their illness is more satisfactory. PMID- 1302334 TI - [Characteristics of early and late onset of schizophrenia]. AB - Two groups of patients derived from paranoid schizophrenia population of Mokotow were compared. The early onset group (before 25th year of age 57 persons) and late onset group (after 40 year of age 48 persons). Characteristics of the course of illness in both groups were compared with respect to productive symptomatology and adaptation. The course of illness was more favorable in the case of late onset psychoses (shorter relapses, longer improvements, fewer hospitalizations, better adaptation). In late schizophrenias the productive symptoms were more often directed towards environment and identity and consistency less frequent. These differences were interpreted as differences in mechanism of personality integration with paranoid syndrome in early and late onset schizophrenia. PMID- 1302335 TI - [Stress, depression and schizophrenia in view of psychoimmunology]. AB - The authors discuss the influence of stress on the immunological system. They describe changes in this system in depressive and in schizophrenic patients and analyze the eventual effect of these changes in the pathogenesis of endogenous psychopathology. The authors conclude that despite the fact that research into the immunology of these aspects are in the beginning stages, the data so far collected indicate a promising result. PMID- 1302336 TI - [Dexamethasone suppression test in endogenous depression and schizophrenia in male and female patients]. AB - Dexamethasone Suppression Test was performed during an acute phase in 81 patients with endogenous depression and 105 schizophrenic patients. The lack of suppression of cortisol was found in 1/3 if those ill with depression and 1/3 of those ill with schizophrenia. A relationship between those results and age was shown in female schizophrenic patients. In both groups a yearly rhythm was observed, however female patients differed from male patients. PMID- 1302337 TI - [Comparison of the concentration of "depressive cognitive factors" in patients with various levels of depression]. PMID- 1302338 TI - [The levels of folic acid and vitamin B12 in the plasma of patient hospitalized with mental illness (literature review and pilot study]. AB - 47 hospitalized patients on the Second Clinic were assessed for levels of vitamin B12 and folic acid. Insufficient amounts of vitamin B12 were found in 21 patients (44.7%) and insufficient levels of folic acid were found in 23 patients (48.9%). PMID- 1302339 TI - [Treatment effectiveness predictors in patients with alcohol dependency]. AB - Research was conducted on 220, 40 year old patients with a history of treatment for alcohol dependency. The prognosis of treatment effectiveness was based on a model of multiple regression. Five prognostic indices were discovered which explained 65% of total variation of the criterion variable. PMID- 1302340 TI - [The influence of disulfiram on the metabolism of ethanol]. AB - The author discusses the metabolism of disulfiram and the enzymes which metabolize ethanol. The restraining of the activity of ALDH in the liver by disulfiram causes an accumulation of acetaldehyde which in their turn cause a series of psychophysical symptoms which are unpleasant and in some instances dangerous for the patient. Thus, it is important to monitor changes in the activity of ALDH after administration of disulfiram. PMID- 1302341 TI - [Analysis of the reversibility of CT brain changes in alcohol dependent patient]. AB - Control CT assessments of the brain of 15 alcohol dependent patients who showed an improvement in their clinical state were performed after a mean of 16 months. A partial decrease of the widening of cerebral sulci and the third ventrical was noticed. Also, the neuroradiological pictures of the vermis and cerebellum were seen to improve in most patients. PMID- 1302342 TI - [Mineralogic research of bone union formation after transplantation of autogenic bone marrow and stromal cells into the bone defect from in vitro culture. Experimental studies. III]. AB - In experimental studies on 3 groups of rabbits (1. with autogenic bone marrow transplantation, 2. with stromal cells from in vitro culture transplantation, 3. control group) the mineralogic changes within healing fracture have been observed. These changes were investigated with scanning microscope and chemically using Cameca electronic microprobe and X-ray diffractometer. In each group there were differences in the time of arising of trabecular structures and their mineralization. Bone trabeculae were visible first in a group of rabbits with performed transplantation of stromal cells. They were present in a great number and their structure was homogeneous. They contained prominent quantity of apatites similar to the one found in normal bone. In the final phase of observation, trabeculae of external part of union demonstrated a parallel orientation and a tendency to transformation into a compact bone. After some time trabeculae arose in rabbits after autogenic bone marrow transplantation. They were less numerous and their structure was disordered. They were characterized by a significant chemical heterogeneity. The content of Ca and P was similar to their content in a normal bone. At the very and trabeculae arose in the control group. Their structure however was heterogeneous. In the final phase of observation the content of Ca and P did not reach the level found in a normal bone. Within the whole bone union a spongy bone arose. PMID- 1302343 TI - [Effect of autogenic bone marrow transplantation into the fracture on acceleration of long bone healing. IV]. AB - 20 cases of long bones fractures healing after autogenic bone marrow transplantation have been observed. The mean age of patients was 39.7 years. Bone marrow was taken from iliac bone and after addition of heparin transplanted percutaneously into the fracture. The bone union was observed in all the cases after the mean period of 2.5 months. The observation performed on the patients treated with bone marrow cells injection and some patients from a control group treated with traditional methods revealed that marrow cells promote acceleration the process of healing. PMID- 1302344 TI - [Congenital malformations in autopsy from the years 1986-1990 of children up to 1 year of age in the region of North-East Poland]. AB - The authors retrospectively analysed 901 autopsy protocols of children up to 1 year in years 1986-1990. Congenital malformations were presented in 364 cases (40.4%). The most frequent anomalies were: multiple anomalies-32.7%, the cardiovascular malformations -32.1% and malformations of nervous system-22.2%. 235 (64.8%) cases of congenital malformations were presented in neonates. There was no significant difference in incidence of congenital malformations between girls and boys. The frequency of congenital anomalies in autopsy material increased from 27.5% (1976-1985) to 40.4% (1986-1990). PMID- 1302345 TI - [Concentration of C3 in sera of small for gestational age newborns in relation to sex and degree of hypotrophy]. AB - 36 small-for-date newborns both sexes with body weight below 10 percentiles were included to our studies. To control group we have enrolled 33 newborns in the same fetal age. We conducted the present study to address whether fetal hypotrophy induce or not decrease of the concentration of C3 in sera of these newborns. Despite of our expectations we have found there is increase C3 in sera in relation to the degree of hypotrophy. We have noted the concentration of C3 is not related to the sex both small-for-date newborns and newborns. PMID- 1302346 TI - [Intraoperative angioscopy]. PMID- 1302347 TI - [Antiplatelet drugs]. PMID- 1302348 TI - [Antiplatelet drugs in the treatment of glomerulonephritis]. PMID- 1302349 TI - [Blood gas analysis--problem of diagnostic quality assurance]. PMID- 1302350 TI - [Progress in insulin therapy. V. Insulin therapy in noninsulin dependent diabetes mellitus]. PMID- 1302351 TI - [Influence of lovastatin on serum lipids in patients with primary hyperlipidemia phenotype IIa and IIb. I. Efficacy of lovastatin in the treatment of hyperlipoproteinemia]. AB - 30 male patients, aged 18-70 years, with primary hyperlipoproteinemia (HLP) IIa (20 persons) and IIb (10 persons), with total serum cholesterol concentration above 6.5 mmol/l and triglyceride concentration below 3.9 mmol/l were treated with lovastatin for 12 weeks, after 4 weeks of wash-out and 4 weeks of placebo period. The lovastatin dosage varied from 20-80 mg daily. There were significant differences between groups in serum triglyceride, HDL-cholesterol and apolipoprotein AI concentration. After 12 weeks of treatment in patients with type IIa as well as with type IIb HPL significant decrease of total cholesterol (by 26.8% and by 33.6%, p < 0.001); LDL-cholesterol (by 39.1% and by 43.2%, p < 0.001); apolipoprotein B (by 22.9% and by 29.6%, p < 0.001) was found. Significant relationship between apolipoprotein B concentration and dosage of lovastatin was found. There were no differences in concentrations of HDL cholesterol and apolipoproteins AI and AII after treatment. The results of this study indicate that lovastatin efficiently decreases total and LDL-cholesterol concentration and apoprotein B level in patients with hypercholesterolemia as well as with hypercholesterolemia with mild hypertriglyceridemia. PMID- 1302352 TI - [Concentration of selenium in serum of patients with ulcerative colitis]. AB - Selenium deficiency may be implicated in the pathogenesis of some human diseases, including colon cancer. The incidence of carcinoma of the colon is increased in patients with ulcerative colitis. We measured the serum concentration of selenium in 22 patients with ulcerative colitis and 22 sex-, age-, height and weight matched controls. Although no significant difference was found in mean serum selenium between patients and controls (patients: 0.92 mumol/l, controls: 0.79 mumol/l), the serum selenium level decreased with increasing extension of the disease. The differences between serum selenium concentrations in patients with proctitis-sigmoiditis, left-sided colitis and pan-colitis were statistically significant. No correlation was found between serum selenium concentrations and the sex, age, height, or weight of the patients. The inverse correlation between serum selenium concentration and the extension of the disease may be caused by a decreased absorption of selenium from the diseased colon in ulcerative colitis. PMID- 1302353 TI - [Effect of autogenic bone marrow transplantation in fractures on the course of delayed bone union healing. Part V]. AB - 39 delayed bone unions of long bones shafts in 34 patients treated with autogenic bone marrow transplantation into the fracture has been observed. The mean age of patients was 37.8 years. Bone marrow was taken from iliac bone and after addition of heparin injected percutaneously into the fracture. After transplantation, the previous treatment was continued. The bone union was observed in all cases after the mean period of 3.1 months. On the grounds of the performed observations it was found that bone marrow transplanted into fracture site accelerates the healing process of delayed union. PMID- 1302354 TI - [Effect of autogenic bone marrow transplantation with "Zespol" technique of osteosynthesis on non-union healing. VI]. AB - The results of treatment of 25 patients with long bones shafts non-union were showed. Patients were treated with autogenic bone marrow transplantation into non union together with "Zespol" technique of osteosynthesis, without opening of non union. The mean age of patients was 35.4 years. Bone union was observed in all the cases after the mean period 3.3 months since the time of bone marrow transplantation. On the ground of clinical and radiologic observation it was found that combination of autogenic bone marrow transplantation with "Zespol" technique is a simple and effective method of long bones non-union treatment. PMID- 1302355 TI - [Analysis of remission of pulmonary hypertension after mitral valve replacement]. AB - In a group of 32 patients with mitral valve disease and extreme pulmonary hypertension, the efficacy of mitral valve replacement (MVR) was analysed. In all patients hemodynamic and clinical data were obtained and compared before and after operation. After surgery a statistically significant differences (p < 0.01) of the pressure was observed in right atrium and ventricle, pulmonary artery and capillaries, the pulmonary resistance was decreased, the cardiac index was increased. The improvement of hemodynamic parameters correlated well with clinical data. But it has not influenced for return to the job. PMID- 1302356 TI - [Activity of selected enzymes of peripheral blood erythrocytes and serum haptoglobin levels in workers occupationally exposed to styrene and formaldehyde]. AB - In 48 and 30 workers exposed to styrene and formaldehyde respectively activities of erythrocyte acetylcholinesterase lactate dehydrogenase and glucose-6-phosphate dehydrogenase, were determined. Hematocrit, haemoglobin concentration, red blood cell count and serum haptoglobin levels were also determined. Significant decrease in erythrocyte acetylcholinesterase activity in workers exposed to styrene for 61-180 months was stated. Moreover, increased erythrocyte lactate dehydrogenase activity and decreased serum haptoglobin level was found in workers exposed to formaldehyde for 3-24 months. There were no differences in basic hematological parameters and erythrocyte glucose-6-phosphate dehydrogenase activity in both groups studied as compared to the control group. PMID- 1302357 TI - [Fibrinolytic treatment of myocardial infarction. Introduction]. PMID- 1302358 TI - [Fibrinolytic treatment of myocardial infarction. Agents, indications, complications]. PMID- 1302359 TI - [Fibrinolytic treatment of myocardial infarction. Adjunctive therapy]. PMID- 1302360 TI - [Anatomical interests of Ludwik Bierkowski (1801-1860]. PMID- 1302361 TI - [Krakow physicist and Warsaw otolaryngologists]. PMID- 1302362 TI - [Pulmonary cellular proliferation and its control during development of pulmonary hypertension]. PMID- 1302363 TI - [Pancreatic colipase]. PMID- 1302364 TI - [Role of protein kinase C on the regulation of functions of vascular smooth muscles]. PMID- 1302365 TI - [Effects of taurine on the proliferation and differentiation of nerve cells in human brain]. PMID- 1302366 TI - [Regulator factors controlling the cell cycle]. PMID- 1302367 TI - [Cell proliferation regulation and isoenzymes of protein kinase A]. PMID- 1302368 TI - [Anti-sense peptide]. PMID- 1302369 TI - [Human interleukin-6 receptors]. PMID- 1302370 TI - [Non-cholinergic actions of acetylcholinesterases in the central nervous system]. PMID- 1302372 TI - [Use of Foxbase in the data processing of physiological studies]. PMID- 1302371 TI - [Erythromycin: a motilin receptor agonist]. PMID- 1302373 TI - [A study on the location of immuno-suppressive factor(s) in restraint rats and mice]. AB - A serum lymphocyte-proliferation suppressive factor(s) induced by restraint stress over 10 h was found in previous studies in both rats and mice. The present study was undertaken to investigate the sites of its production. The results show that large doses of irradiation and cyclophosphamide (CY) decreased the total number of splenic nucleated cells, but the production of the suppressive factor was inhibited only by irradiation. This indicates that the drop in total number of lymphocytes does not play any key role in the production of the serum suppressive factor. Cell classification showed that the ratio of T to B cell was decreased by radiation but increased by CY, suggesting that this ratio may be relevant to the production of the factor. Inhibition of the production was also observed in nude mouse (an animal showing a lack of T cell activity), again supporting that T cells are involved in the production of the inhibitory factor. PMID- 1302374 TI - [Effect of electrical stimulation of the area postrema on plasma renin activity and renal sympathetic nerve activity in rabbits]. AB - 68 urethan-anesthetized rabbits were prepared for registration of changes of respiration, arterial blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) due to stimulation of area postrema (AP) by rectangular pulse trains each lasting for 4 s for every 30 s. During 40 min of such a stimulation paradigm the venous blood samples were collected for radioimmunoassay of plasma renin activity (PRA) (both pre- and post-stimulation), RSNA registered and processed by a computer. Animals were divided into three groups: (1) with AP stimulation only (n = 47); (2) AP stimulation after bilateral renal denervation (n = 13); (3) AP stimulation after propranolol injection (n = 8). In Group I, a 91% increase in PRA, an augmentation of RSNA, a rise of BP and a decrease of HR were observed, while respiration did not show obvious change. In Group II, hemodynamic and RSNA response was similar to that in Group I, but PRA was not changed significantly. In Group III, the effects on BP, HR, respiration and RSNA showed no remarkable changes compared with Group I, but significant inhibition of the response of PRA [from 0.65 +/- 0.07 ng/(ml.h-1) to 0.72 +/- 0.10 ng/(ml.h-1), P > 0.05] was observed. The results mentioned above suggested that electrical stimulation of AP may induce an increase in renin release and renal sympathetic nerve activity and hemodynamic changes in rabbits. PMID- 1302375 TI - [Effect of electrical stimulation of paraventricular nucleus on stress gastric mucosal lesion in rats]. AB - The effect of electrical stimulation of hypothalamic paraventricular nucleus (PVN) on gastric mucosal lesion induced by RWIS (restraint + water-immersion stress) in rats was investigated. The main results were as follows: (1) Electrical stimulation of the PVN could obviously increase the stress gastric mucosal lesion. (2) Microinjection of L-glutamate into PVN could produce similar effect to that of PVN stimulation. (3) PVN lesion could significantly decrease the stress gastric mucosal lesion. (4) The above mentioned effects were attenuated by vagotomy or atropine injected subcutaneously. (5) A further study indicated that the gastric mucosal blood flow was reduced upon PVN stimulation, but no obvious changes of gastric juice volume, total acid output, pepsin activity and gastric barrier mucus were observed. The results mentioned above indicate that the PVN is one of the specific CNS areas capable of increasing the stress-induced gastric mucosal lesion mediated through the cholinergic fibers of the vagal nerve and related to decreased gastric mucosal blood flow, while gastric acid output, pepsin activity and gastric barrier mucus do not seem to play any important role. PMID- 1302376 TI - [Contraction stimulates incorporation of 3H-leucine and cell growth in cultured neonatal rat ventricular myocytes]. AB - To determine whether contraction could influence cell growth, the rate of protein synthesis (3H-leucine incorporation) and cell diameter and volume were measured in cultured neonatal rat cardiac myocytes beating spontaneously or arrested by high potassium. In medium supplemented with 10% calf serum, the 3H-leucine incorporation for 24 h in contracting myocytes (CMC) was significantly higher by 14.2% than that in quiescent myocytes (QMC), i.e. 1,229 +/- 29 cpm/10(5) cells vs. 1,076 +/- 60 cpm/10(5) cells (P < 0.01, n = 5 for each group). The cell diameter and cell volume in QMC group were respectively 15.14 +/- 0.42 microns and 1,842 +/- 123 microns3, while in the CMC group the corresponding figures reached to 16.82 +/- 0.64 microns3 and 2,495 +/- 210 microns3, increased by 11.1% and 35.5% respectively (P < 0.01, n = 6 for each group). With prolongation of culture time, the differences in these parameters between CMC and QMC became even more significant. In all these experiments, there was no significant difference in cell number between the two groups (P > 0.05). It is concluded that contraction per se can accelerate protein synthesis and cell growth in neonatal rat ventricular myocardium. PMID- 1302377 TI - [Optimal pulmonary ventilation determined by the relation between end-tidal CO2 and arterial blood pressure in artificially respirated cat]. AB - End-tidal CO2 (ET-CO2) provides a continuous and sensitive monitoring of proper pulmonary ventilation in artificially ventilated animals during single unit recordings of the central nervous system. To determine a reliable standard of ET CO2 in anesthetized and paralyzed animal, the relationship between ET-CO2 and arterial blood pressure (ABP) was observed in cat under different ventilation level. The results showed that ABP changed tremendously with variation in ventilation, but remained constant at a normal level as long as ET-CO2 was maintained within the range between 4.0-5.0%, i.e. optimally at 4.5 +/- 0.5%. PMID- 1302378 TI - [Variation of WGA and PNA binding glycoproteins in early pregnant rabbit uterine fluid]. AB - The qualitative and quantitative changes of two kinds of lectin (WGA, PNA) binding glycoproteins in early pregnant rabbit uterine fluid (D4-D12) were measured by Western blot and Video densitometer scanning methods. During peri implantation stage (D6, D7 and D9), there are two WGA binding glycoproteins with MW about 42 kd, 28 kd and a PNA binding glycoprotein with MW 75 kd. It is suggested that the three proteins are stage-specific glycoproteins in rabbit uterine fluid in the course of implantation. PMID- 1302379 TI - [Effect of CCK receptor antagonists on plasma CCK bioassay]. AB - Fasting and postprandial plasma CCK levels of 102 normal subjects were measured by bioassay with dispersed rat pancreatic acini. The reference values ranged from 0 to 4.2 pmol/L (CCK-8 equivalents) for fasting and from 1.1 to 13.5 pmol/L for postprandial state. There was no significant difference between male and female, or in different age groups. The effects of CCK receptor antagonists of 3 different categories on CCK bioactivity in plasma measured by the bioassay were investigated. L 364,718 (5 nmol/L), proglumide (1.0 mmol/L), or Bt2-cGMP (0.1 mmol/L) was either extracted by SEP-PAK C18 cartridges together with human plasma containing 8 pmol/L of CCK-8, or added into the plasma extracts before the assay. The CCK bioactivity was inhibited by all of the 3 CCK antagonists. The action of L364,718 could be eliminated by the procedure of plasma extraction, but not of proglumide or Bt2-cGMP. It was suggested that CCK bioassay can be used even if L364,718 was administered. However, CCK cannot be measured accurately if there are proglumide or Bt2-cGMP in the plasma. PMID- 1302380 TI - Liver transplant in India: miles to go. PMID- 1302381 TI - Hepatocyte transplantation: need for liver cell bank. PMID- 1302382 TI - Orthotopic liver transplantation--western experience & Indian realities. PMID- 1302383 TI - Management options for pancreatic pseudocysts. AB - Between July 1987 and February 1990, 42 patients with pancreatic pseudocysts were treated. In 83% the pseudocyst was related to alcohol. Patients were managed by observation (7), surgical external drainage (7), and internal drainage (12). Fifteen patients were treated by ultrasound guided percutaneous catheter drainage (UGPCD) with apparent success in 67%. In 5 of these UGPCD was abandoned because of either prolonged drainage or infection of the pseudocyst. In patients with recurrent pseudocysts or in those with failed UGPCD, the cystic collections were successfully drained internally in 16 out of 17 patients (94%). Internal drainage appears to be acceptable treatment for mature pseudocysts, recurrent pseudocysts or for failed UGPCD, provided there is no downstream pancreatic duct obstruction or duct dilatation. If either exist, resection or direct ductal drainage will be required. PMID- 1302384 TI - Influence of intraperitoneal drainage after cholecystectomy; a prospective ultrasonographic study. AB - One hundred and fifty patients were prospectively randomised into 3 groups (50 in each group); to receive a passive drain, closed suction drain or no drain after elective cholecystectomy. The drain was removed within 24 hours in 84% of patients and was continued longer only if the amount of drainage was excessive or bilious. On the 3rd post-operative day, an ultrasound examination was performed in all patients for detection of subhepatic/subphrenic collection. Collections were more frequently encountered in the patients without any drain (42%) followed by passive drain (26%) and suction drain group (20%). Chest complications were frequently noted (passive drain; 6% suction drain, 12%, and no drain, 8%), however, occurrence of this complication in various groups was similar (p > 0.1). Two patients (4%) without drain required ultrasound guided aspiration of subhepatic collection. Mean post-operative hospital stay was nearly equal for all the groups (passive drain: 4.22 +/- 1 days, suction drain: 4.26 +/- 1.4 days and no drain: 4.62 +/- 2.3 days). Drainage reduced the incidence of post cholecystectomy collections and need for invasive intervention for collection related complications. However, the type of drainage (active or passive) did not influence the incidence of collection, frequency of complications and duration of post-operative hospital stay. PMID- 1302385 TI - Encephalomyelopathy following portocaval shunt in noncirrhotic portal fibrosis: a case report. AB - A 30 year old male patient presented with the clinical picture of progressive encephalomyelopathy eleven years after a portacaval shunt for non-cirrhotic portal fibrosis (NCPF). The spinal cord involvement in this patient was restricted to the corticospinal and the spinocerebellar pathways. The clinical picture and neuropathology of encephalopathy and of myelopathy have been described in patients with cirrhosis. Cases of encephalopathy and myelopathy have also been reported following shunt surgery in NCPF. We report the first case of encephalomyelopathy developing eleven years after portacaval shunt in a patient with noncirrhotic portal fibrosis. PMID- 1302386 TI - Splenic hamartoma with portal hypertension: a case report. AB - A case of splenic hamartoma arising from the upper pole of the spleen and presenting with upper abdominal pain, ascites and pedal edema is presented. Splenectomy was performed. The histopathology, revealed splenic hamartoma of pulposal type. PMID- 1302387 TI - Sclerosing cholangitis and biliary calculi: primary or secondary? PMID- 1302388 TI - Complications of laparoscopic cholecystectomy. PMID- 1302389 TI - Vaccines: modern approaches and immunology. PMID- 1302390 TI - [Cytofluorimetric research on the content of glycogen and its fractions in the hepatocytes of patients with liver cirrhosis of different etiologies]. AB - By cytofluorometric method, a study was made of the total glycogen and its two fractions in liver parenchymal cells both in the donors (20 men) and in patients with cirrhosis of different etiology (39 men). The examination was performed on preparations--smears of isolated hepatocytes, obtained from the live functional liver biopsies. The quantitative analysis has shown an increase in the total glycogen content in hepatocytes of patients with cirrhosis by 3 times compared to the norm, and this increase is independent on the etiology of liver cirrhosis. To study the mechanism of the discovered glycogenosis, the activity of key enzymes of glycogenolyses was determined. It was shown that glucose-6-phosphatase and glycogen-phosphorylase activity in the liver with cirrhosis was lower than in the norm. The most considerable changes were shown in hepatocytes of patients with liver cirrhosis in fractional glycogen composition and, even more significant, in the content of a hard soluble fraction. The hard soluble fraction portion was higher in hepatocytes of the patients with liver cirrhosis of alcohol etiology. The quantitative analysis of glycogen fraction contents in liver cells may be the best marker in the differential diagnosis of symptomless elapsing liver cirrhosis. PMID- 1302391 TI - [A simple method of preparing permanent squash preparations using cellophane]. AB - A technique to prepare permanent squashed preparations of cell nuclei and chromosomes is proposed. Fix a piece of material on the slide with acetic alcohol (1:3), macerate with a 45% acetic acid, cover with hydrophilic cellophane previously soaked in a 45% acetic acid and then with a cover slip and filter paper to squash finally as it is routinely performed. After that soak off the cover slip with alcohol, post-fix the squashed preparation together with cellophane in alcohol for 5-10 min, unstick the cellophane, pass the preparation through alcohol once again and dry it. The subsequent treatment of the squashed preparation depends on the purpose of investigation. The slide may be tinctured overlaid with photoemulsion for autoradiography, or processed by different ways. PMID- 1302392 TI - [Changes in the relative arrangement of the chromosomes and nucleolus in developing mammalian oocytes during meiotic prophase I in relation to functional changes in the oocytes]. AB - Data on chromosome transformation in meiotic prophase I during mammalian oogenesis are summarized. The main peculiarity of the female meiosis in mammals is an unusually long diplotene stage which may be subdivided into four periods: 1) the early diplotene (up to the beginning of follicle formation); 2) the dictyotene or "diffuse diplotene", implying primordial follicle oocytes; 3) the most pronounced lampbrush chromosome stage coinciding with the large growth period; 4) the stage of chromosome inactivation and karyosphere formation corresponding to the terminal stage of oocyte development before ovulation. These stages are associated with changes in the transcriptional chromosome activity. A correlation is revealed between the spatial chromosome arrangement in the oocyte nucleus and the transcriptional activity. Some regularities are followed in the transformation of the main nucleolar component arrangement during meiotic prophase I in mammalian oocytes. At the late pachytene and at the early diplotene, a segregation of the main nucleolar components has been observed. These components are disposed in the direction: chromatin--fibrillar center- dense fibrillar component--granulo-fibrillar component. At the dictyotene, signs of nucleolar segregation are still observed. At the lampbrush chromosome stage, when the nucleus is most highly transcriptionally active, an integration of nucleolar components occurs. At the late diplotene--prediakinesis stage, i.e. in the course of transcriptional activity lowering and karyosphere formation, the secondary segregation of the main nucleolar components occurs. These move to the nucleolar periphery to be disposed around a large fibrillar mass which is gradually displacing the rest of the nucleolar components. The fibrillar mass formation in the preovulatory oocyte nucleoli is one of the peculiarities of the diplotene and prediakinetic mammalian oocytes. PMID- 1302393 TI - [The morphogenetic potentials of endometrial and ovarian tumor cells when cultured on soft agar]. AB - Morphofunctional peculiarities of tumor cells from 15 endometrial adenocarcinomas and 2 ovarian tumors have been investigated at the ultrastructural level. These cells could develop two types of colonies in soft agar: those with histotypical differentiation (numerous microvilli, well developed tight junctions, desmosomes, secretory granules), and those without it (absence of epithelial features, ability of tumor cells to produce filamentous extracellular matrix and striated collagen fibrils which are characteristic of fibroblastic cells). The addition of progesterone and tamoxifen to cell cultures resulted in rising the level of cell differentiation in the colonies. The fact that endometrial and ovarian cancer cells can express the properties specific of connective tissue cells may suggest a multipotention of the Mullerian epithelium derivatives to shed light on the histogenesis of the mixed Mullerian tumors of uterus. PMID- 1302394 TI - [Polyploidy and polyteny in the trophoblast cells of the mink]. AB - According to cytophotometry, trophoblast cells in the mink placenta are both diploid and polyploid, the ploidy level ranging from 2c to 64c. A great number of mink trophoblast cells were seen to divide mitotically. In addition to the ordinary mitotic figures, polyploid mitoses as well as abnormal mitotic figures were observed. Non-classic polytene chromosomes, peculiar to the mammalian trophoblast, appeared in the mink trophoblast cells to have the highest ploidy. A relatively low ploidy degree is due, probably, to a lesser invasive activity of the mink trophoblast cells as compared to the rodent giant trophoblast cells. PMID- 1302395 TI - [The interaction of epidermal keratinocytes and fibroblasts during the formation of a live skin equivalent]. AB - The effect of human fetal fibroblasts and adult keratinocytes on collagen contraction was studied. Keratinocytes embedded in collagen lattices did not spread and produced only a slight contraction. When keratinocytes were seeded on the surface of tht gel, the contraction began within 24 h and correlated with the formation of epithelial colonies. Transplantation of multilayered epithelial sheets on the gel significantly accelerated the onset of contraction. Keratinocytes seeded on and fibroblasts grown in collagen lattices cooperatively contracted the gel, and keratinocytes were able to stimulate gel contraction even when they had no contact with the collagen roughly populated with fibroblasts. Swiss 3T3 cells remained spherical in collagen lattices and did not contract the gel but when cultivated with keratinocytes they stimulated gel contraction. In their turn, keratinocytes influenced the behaviour of Swiss 3T3 cells which elongated and produced processes. We suggest that both keratinocytes and mesenchymal cells can affect gel contraction 1) by a direct contact with collagen lattices, and 2) through potentiation of the ability of another cell type to contract the gel. PMID- 1302396 TI - [The role of high-mobility-group proteins (HMG proteins) in the structural functional organization of the chromatin in rat cardiomyocytes]. PMID- 1302397 TI - [Survival and the repair of single-stranded DNA breaks in gamma-irradiated Escherichia coli cells adapted to methylmethane sulfonate]. AB - The survival and repair of single-strand breaks of DNA in gamma-ray-irradiated E. coli adapted to MMS (20 mkg/ml during 3 hours) have been investigated. It is shown that the survival of adapted bacteria of radioresistant strains B/r, H/r30, AB1157 and W3110 pol+ increases with DMF (dose modification factor) ranging within 1.4-1.8 and in radiosensitive strains Bs-1, AB1157 recA13 and AB1157 lexA3 with DMF ranging within 1.3-1.4, and does not change in strains with mutation in polA gene P3478 polA1 and 016 res-3. There is no increase in radioresistance during the adaptation to MMS under the action of the protein synthesis inhibitor chloramphenicol. The increase in radioresistance during the adaptation to MMS correlates with the acceleration of repair of gamma-ray-induced single-strand breaks in the radioresistant strains B/r and W3110 pol+ and with the appearance of the ability to repair some part of DNA single-strand breaks in the mutant Bs 1, which beyond the adaptation to MMS does not repair these damages. The incomplete reparability of DNA single-strand breaks in P3478 polA1 strain cells, both adapted and non-adapted to MMS, is equal. PMID- 1302398 TI - [Cytofluorimetric research on the changes in the DNA content in the nuclei of Amoeba proteus during prolonged starvation and after refeeding]. AB - Dividing amoebae were manually selected from the culture of Amoeba proteus, and so groups of synchronously dividing (synchronized) amoebae were obtained. These synchronized amoebae were maintained without food. In spite of starvation, individual amoebae in some particular groups were seen to divide, whereas in other groups of amoebae there was no division at all. The starving amoebae died not earlier than 2 weeks after the last division. A relative DNA content in isolated nuclei has been determined cytofluorometrically for each of 6 groups of synchronized starving amoebae, unable to divide. The nuclei were isolated in different intervals after division (after the feeding was ceased): 1.0-1.5 h, 1 day and up to 13 days with 1-2 day intervals. In the all groups of amoebae DNA synthesis occurred on the first 1-2 days after division. The nuclear DNA content in amoebae of 3 groups increased more than two-fold as compared with the 1 h level, in other 3 groups the nuclear DNA content did not exceed the doubled 1 h level, but probably exceeded the doubled postmitotic level. Later on, the nuclear DNA content in starving amoebae of each group was seen to decrease by 16-20%. Amoebae of 3 of the 6 groups were given the food organisms (Tetrahymena pyriformis) 8 days after division (after cessation of feeding). 2-3 days after refeeding some of these amoebae divided, and the nuclear DNA content of the refed amoebae proved to be higher than that in amoebae that continued to starve. It is suggested that the decrease of DNA content in the nuclei of starving amoebae and the increase of DNA quantity in the nuclei of refed amoebae may result from degradation and induction of synthesis of specific extra DNA synthesized in amoeba nuclei during each cell cycle. PMID- 1302399 TI - [Acute renal failure]. PMID- 1302400 TI - [Recurrent urethral strictures in men. Modern diagnosis and therapy using ultrasound and laser]. AB - The new method of urethral sonography allows visualization of urethral strictures preoperatively in more detail than conventional X-ray urethrogram. Poor results of urethrotomies can thus be avoided in patients who have peristrictural scars. These patients can be treated by the newly developed technique of laser incisions of urethral strictures. The success rate is so promising that wall-stent implantations and even open procedures may well become very rare. Diagnostic and therapeutic techniques are discussed and described in detail with reference to illustrations. PMID- 1302401 TI - [Internal urethrotomy]. AB - Internal urethrotomy is the first treatment for all kinds of urethral strictures except meatal stenosis and complete urethral obstruction. After urethrotomy a urethral catheter is left indwelling for up to 3 days if the urine is already sterile. In the case of infection it remains in place for 2 weeks. Long-term results depend mainly on the extent of periurethral fibrosis. The over-all success rate is about 50%. Only in a few cases can a second or third urethrotomy be definitively curative. Further urethrotomies are clearly only a palliative treatment of the stricture, comparable in effect to repeated urethral dilatation. PMID- 1302402 TI - [One-stage urethra repair with end-to-end anastomosis]. AB - The direct anastomosis in one session is the method of choice for the treatment of urethral strictures (< 2.5 cm length) when at least three internal urethrotomies have failed. If certain important details are kept in mind about the operative technique (wide anastomosis without tension), suitable suture materials used, and the urinary diversion is done without placing a burden on the anastomosis, the long-term results are good. The direct anastomosis and operative approach can be varied according to the special situation in individual cases. The analysis of 47 patients operated on with direct anastomosis for strictures in the posterior urethra (28 post-traumatic, 9 iatrogenic, 10 postinflammatory) revealed that 83% of the patients had good or satisfactory results, while in 8 patients (17%) the results were poor. The poorist long-term results occurred in post-traumatic strictures in the bulbomembranous part of the urethra connected with complicated pelvic fractures. PMID- 1302403 TI - [Pedicled penis skin flap for unilateral correction of extensive urethral strictures including meatus reconstruction]. AB - Many techniques have been described for the repair of recurrent urethral strictures. We report our experience with the use of vascularized island skin flap repairs of urethral strictures as a one-stage procedure in 24 patients and describe the rationale for selection of the procedure, surgical technique used, results and complications. Using the pedicled penile island flap and the inner preputial skin one-stage correction is possible in urethral strictures up to the tip of the penis. The combined use of scrotal skin increases the risk of complications and thus should be avoided. Meatal reconstruction as described by De Sy gives excellent functional and cosmetic results. PMID- 1302404 TI - [Anatomy of the posterior urethra]. AB - The short section of the urethra that passes through the urogenital diaphragm is termed the membranous urethra. It is accompanied by several vessels and nerve fibers. In surgery on the membranous urethra the perineal body is of crucial importance, and precise knowledge of the course of the urethra through the pelvic floor is essential. Furthermore, the relationship between the membranous urethra and its accompanying structures is of great importance. These include the branches of the internal pudendal artery, the prostatic venous plexus and the cavernous nerves coursing ventrally from the pelvic plexus. The nerves supplying the membranous urethra were studied in fetuses with the help of a magnifying lens. The results of the dissections are documented by histological sections, photographs and paintings. PMID- 1302405 TI - [Urethral rupture--primary repair and reconstruction]. AB - Whether the posterior urethra can successfully be reconstructed depends mainly on the primary care, especially in the case of strictures secondary to trauma. Prior to surgery, primary care of the lesion is mandatory, including open suprapubic fistula, drainage of the cavum retii and of the perineal space, repositioning of the urethra and immediate stabilization of the pelvic ring by means of elastic procedures. In a second step, between 1978 and 1990 we performed bulbo-prostatic surgery in 27 patients with traumatic rupture of the posterior urethra. Based on extensive anatomic be studies on the relationship of the membranous urethra to the pelvic floor and to the arteries, veins and nerves, an operative approach via the perineal body was developed. Of 18 patients followed up, only 4 had flow rates of less than 15 ml/s. Retrograde urethrograms and micturition cystograms showed good results. PMID- 1302406 TI - [Stabilization of pelvic fractures]. AB - In contrast to less complicated injuries to the pelvic ring, unstable bony fractures and injuries caused to ligaments by high-energy trauma require immediate stabilization by internal fixation. Since patients with severe pelvic injuries commonly present with multiple trauma, close cooperation between different medical disciplines is necessary to provide for optimum patient management. In cases with concomitant urological injuries, a joint primary intervention is recommended. Whether anterior, posterior or combined approaches are indicated for internal fixation depends on the injury pattern. The classification of pelvic ring fractures into group A, B and C injuries is discussed in detail. PMID- 1302407 TI - [Mesh graft urethroplasty]. AB - Since 1977 124 patients with complicated urethral strictures have been treated by using free-foreskin grafts or split-thickness skin grafts to construct a neourethra in a two-stage procedure. Excellent functional and anatomical results have been achieved in 115 patients. The technique is even useful in exceedingly long or problematic strictures, such as in patients with spinal cord injuries. PMID- 1302408 TI - [Wall-stent for treatment of bulbar urethral stricture and DSD in spastic bladder]. AB - Since may 1989 a urethral Wallstent has been used for the treatment of short urethral strictures and for DSD in paraplegic patients with reflex bladder activity. Forty-nine patients have now been followed-up, which exceeds the 6 month margin. Out of these, 25 suffered from a short stricture of the bulbous urethra and 24 had spastic bladders with severe DSD. Eighteen of the 25 patients with strictures had previous unsuccessful direct vision urethrotomies; 17 in the DSD group had undergone failed sphincterotomies. In all but 2 cases the infravesical obstruction could be treated effectively solely by stent implantation. The results obtained equal those of a well-performed end-to-end anastomosis of the bulbous urethra or a 12, o'clock sphincterotomy. PMID- 1302409 TI - [Clinical experience with BCG immune prevention in superficial bladder cancer]. AB - Previous randomized studies have shown that in cases of superficial urothelial carcinoma or carcinoma in situ of the urinary bladder, complete and long-lasting remission can be obtained by immunotherapy with bacillus Calmette-Guerin (BCG). Such studies have shown that BCG reduces the recurrence rate significantly compared with transurethral resection alone. Our 6-year experience with BCG Pasteur strain (and Connaught strain, respectively) in tumour stages pTis, pTa and pT1 (G I-II) shows lasting remission in 88.5% (73%) of 78 (26) patients after transurethral resection of the tumour. A complete remission was found in 92% of patients with carcinoma in situ (12 patients). The local and the rare systemic side effects were all of limited duration, tolerable, easily treated and fully reversible. PMID- 1302410 TI - [Varicocele in childhood. Treatment indications and value of sclerotherapy]. AB - Varicocele is the most common surgically correctable cause of male subfertility. The incidence of varicocele is about the same in adolescents as in men (16.3%). Percutaneous transfemoral sclerotherapy has been performed in 42 of the authors' own cases; it is an alternative to surgical ligation of the varicocele and should be recommended whenever a varicocele is found, to prevent gonadotoxic damage. PMID- 1302411 TI - [Incidental detection of renal cell cancer]. AB - In the present study, a comparative analysis of clinical-prognostic factors in symptomatic and incidentally found renal cell carcinomas is evaluated. A total of 141 patients with renal cell carcinoma were analyzed according to the TNMG system and involvement of the adrenals. More than 50% of surgically treated renal cell carcinomas are found incidentally. Prognostically, this group has advantageous factors. PMID- 1302412 TI - [Combined ultrasound-urodynamic study in paraplegic patients]. AB - Over a period of 2 years (1989-1991), combined urodynamic and ultrasonic investigations of the lower urinary tract were performed in 80 patients with spinal cord injuries. The main advantage of this procedure proved to be the lack of irradiation to both patient and investigator. Besides the real-time image of the bladder, bladder neck, prostate, pelvic floor and urethra, functional conclusions were possible, especially when urodynamic pressure curves were also considered. PMID- 1302413 TI - [Hamartoma polyps of the urethra]. AB - Fibroepithelial polyps are rare benign tumours that can cause obstruction of the urethra. Most such polyps occur during childhood. We present two patients, one is a child, the second an adult male. The problematic diagnosis is emphasized. PMID- 1302414 TI - [Prospective randomized multicenter phase IIB study in patients with mumps orchitis]. PMID- 1302415 TI - [The glycogen and lactate content of the white and red muscles in fishes with differing natural mobilities during experimental swimming]. AB - Glycogen content of muscles has been investigated in moderately motile fishes during burst and cruising swimming, as well as in fast swimming fishes during burst swimming. It was shown that the intensity of glycogenolysis in muscles depends on the swimming regime and natural adaptation of fishes to physical loading. During burst swimming, significant decrease in glycogen content was found in both white (up to 70%) and red muscles (up to 50%) of fishes with moderate natural motility, in contrast to fast swimming fishes in which glycogen content decreases only in white muscles (by 30%). Cruising swimming in moderately motile fishes results in practically equal decrease of the glycogen content in both types of muscles (by 80-85%). The mentioned specificity of metabolism in fishes with moderate motility, as well as peculiarities of morphological organization of their skeletal muscles (the mass of red muscles amounts up to 5%), suggest that the main locomotor organ in these species is presented by white muscles. PMID- 1302416 TI - [A comparative study of the substrate and inhibitor specificity of the glutathione transferase from the spring grain aphid (Schizaphis gramina Rond.) and from rat liver]. AB - Kinetic parameters of 9 substrates interaction with glutathione transferase (GST) from spring grain aphid and rat were studied. The most significant difference in Vmax values was noticed for 4-nitropyridine-N-oxide (6 times higher for aphid) and ethacrynic acid (7 times higher for rat). Km values were practically in all cases higher for aphid GST as compared to rat GST. New class of effectors of GST suggested by us, that is azimines (2 series), was used for the inhibitor analysis. GST interaction with these inhibitors was appreciated by three types of activity: nucleophilic replacement, thiolysis and N-deoxygenation. It has been shown that the degree of GST inhibition depended considerably both on the GST source and the substrate used. New high-effective inhibitors of GST were found among azimines and their higher specificity to rat GST as compared to aphid GST was demonstrated especially in thiolysis reaction. PMID- 1302417 TI - [The fever reaction of the polecat Mustela putorius x Mustela putorius furo to a bacterial pyrogen: the hypo- and hyperthermic phases]. AB - It has been demonstrated that the ferret (Mustela putorius x Mustela putorius furo) responds to intramuscular injection of Salmonella typhi lipopolysaccharide (30 ng/kg-100 micrograms/kg) by biphasic change in the body temperature (Tb): the initial decrease in the latter is followed by hyperthermia. Maximum rise in Tb (1.6 +/- 0.1 degrees C) was observed after the injection of lipopolysaccharide in the highest dose. Rabbit leucocytic pyrogen/interleukin-1 (1 ml from 3.5 x 10(7) peritoneal phagocytes, 3 ml/kg) induces a pronounced (1.1 +/- 0.3 degrees C) decrease in Tb. Mechanisms of hypothermic effects of pyrogens are discussed. The described pattern (hypothermia-hyperthermia) of Tb response to lipopolysaccharide in the ferret presumably reflects the central thermoregulatory process which is the same for different changes in Tb during fever. PMID- 1302418 TI - [A comparative study of the DNA structural damages and synthesis in embryos of the silkworm Bombyx mori irradiated with gamma rays at different developmental stages]. AB - Studies have been made on formation and reparation of apurine-apyrimidine (AP) regions, monothread DNA ruptures, as well as on inhibition and recovery of DNA synthesis in gamma-irradiated 3- and 7-day embryos of the silkworm which sharply differ in their radiosensitivity. It was shown that in 3-day embryos, the number of AP regions and DNA ruptures immediately after irradiation is significantly higher than in 7-day embryos. DNA synthesis is more radiosensitive in 3-day embryos as compared to that in 7-day ones. Kinetics of postradiation recovery of regions and DNA ruptures in 3- and 7-day embryos is heterogeneous and significantly different. However, radiation inhibition and postradiation recovery of DNA synthesis in irradiated 3- and 7-day embryos are associated mainly with postradiation survival of these embryos. PMID- 1302419 TI - [Malondialdehyde can control cell division at the DNA replication stage (a hypothesis)]. PMID- 1302420 TI - From puberty to mid-life: a follow-up study of twins and controls. AB - During the years 1964 to 1971 a group of twins and a control group of singletons in the same classes, were followed from grade 3 at 10 years of age to grade 9 at 16 years of age in the Swedish compulsory school. The study was called the SLU project (Skoloverstyrelsens och Lararhogskolans Utvecklingsprojekt) and the main purpose was to study physical and mental growth during puberty as well as heredity and environment influences on these growth processes. Originally 323 twin pairs, MZ and DZ, and 1193 controls were included in the sample. Among the DZ twin pairs there were both same-sex and opposite-sex pairs. They were a nationally representative sample. Several kinds of information were collected, such as, a) Physical measurements (height and weight measurements, menarche, ratings of secondary sex characteristics); b) Ability and achievement measures (intelligence tests, standardized achievement tests); c) Self ratings; d) Ratings by teachers and classmates; e) Socioeconomic background data (fathers occupation and income). For the boys, supplementary data on physical growth and mental ability was collected on enrollment to military service at the age of 18. In this pilot-study, we have made a follow-up of the original SLU-sample after 20 years. They are now in their mid-thirties. The main purpose has been to investigate if they are willing to participate in a new study on health and well-being at mid life. PMID- 1302421 TI - A twin study of odor identification and olfactory sensitivity. AB - Interindividual variation in odor identification and olfactory sensitivity has been explained primarily with reference to age, sex and/or experiential factors. A twin study of olfaction can, therefore, substantially contribute to current research in this area. Thirty-nine monozygotic and twenty dizygotic twin pairs have completed the University of Pennsylvania Smell Identification Test (UPSIT), an olfactory preference questionnaire, and two odor detection threshold tests (phenyl ethyl alcohol and butanol). A genetic influence on odor identification, as assessed by the UPSIT, has been demonstrated. Future plans and directions for this research program are discussed. PMID- 1302422 TI - Temperament prediction for neonate twins: relation to size for gestational age in same-sex pairs. AB - Infants from 22 pairs of appropriate-for-gestational-age/small-for-gestational age (AGA/SGA) same-sex twins were assessed for temperament stability between the neonatal period and 30 months of age. The evaluation of neonatal temperament included observers' ratings of irritability, resistance to soothing, activity level while awake, activity level during sleep, reactivity, and reinforcement value. At 6, 9, 12, 18, 24, and 30 months mothers rated their infants' temperament on standardized questionnaires which yielded nine temperament categories: activity level, rhythmicity, approach or withdrawal, adaptability, intensity of reaction, quality of mood, attention span, distractibility, and threshold of responsiveness. The Bayley Scales of Infant Development were administered at 6, 9, 12, 18, 24, and 30 months to assess mental development. The results of longitudinal correlational analyses indicated that, for the AGA infants, there was a pattern of significant predictive relations between the neonatal ratings of temperament and maternal ratings of temperament at 6, 9, 12, 18, 24, and 30 months. The SGA infants did not demonstrate similar behavioral stability from the lying-in period up to 30 months of age. Furthermore, for AGA infants there was a consistent trend for both reactivity and neonatal activity during sleep to predict mental development scores between 6 and 30 months. A similar pattern was not observed for the SGA cotwins. The results indicated that temperament stability is an additional area of risk for SGA twins, and that the developmental function of the underlying processes in the neonatal measures is different for AGA and SGA infants. PMID- 1302423 TI - Twin umbilical cord blood gas values. AB - In vaginally delivered births (including a few cases where the mothers were under epidural anesthesia), differences between first and second born twins were compared according to presentation at delivery. Of twins with vertex/vertex presentation in 15 primipara cases and in 14 multipara cases, pO2 levels for the second born were significantly lower (both being p < 0.05) than for the first born. Of twins vertex/non-vertex presentation, the second born in 9 primipara cases showed significantly lower pH, pO2 and HCO3 levels (p < 0.05). Also for multipara twins, the second born had significantly lower pH (p < 0.05) and significantly higher pCO2 (p < 0.05) values. Umbilical cord blood gas value findings indicate unfavourable conditions for second born twins. PMID- 1302424 TI - Effects of early mother-twin relationships from birth to age 3, on twin bonding. AB - Findings from an earlier phase of this research project clearly pointed to the mother's psychological adaptation inherent to the specificities of triadic interaction. Mothers' attitudes were classified in a typology ranging from "early twinness" where the two babies are treated as though they were a single unit, to attempt to create two dyadic relationships. The current program deals with the effects of the type of parent-child relationship at one year on the emergence of twin bonding. Sixty-eight families of twins (26MZ, 24DZ same sex, 18DZ different sex) are followed up from birth to the age of 3 using a method based on clinical interviews, videotaped observations, and questionnaires. The data cover mothers' rearing attitudes towards organization of babycare and outward signs of twinness, maternal representations of the relationship between the twins and observation of the children's interaction in a standardized game situation. The findings are discussed in terms of zygosity, and parental SCS. PMID- 1302425 TI - Perinatal management of twin pregnancy. AB - Of 104 cases, 38 (ie, 36.53%) experienced premature delivery (controls: 4.32%). In instances of threatened premature delivery, 28 cases (26.92%) underwent ligation of the cervix. EPH gestosis occurred in 62 cases--a high incidence rate of 59.61% (controls: 12.9%). Forty-nine cases (47.11%) were complicated by anemia (controls: 8.36%). There were 57 cases of SFD infants, again a high 27.40% incidence rate (controls: 5.94%). Apgar scores of 7 or less at 1 minute after birth indicated that of the 208 neonates, the second-born twin only in 20 cases (9.61%); both infants in 14 cases (6.73%); and, the first-born only in 3 cases (1.44%), developed asphyxia neonatorum. Given the high incidence of premature and immature infants in cases of twins, caution should be employed against threatened premature delivery from around the 28th week of gestation onwards. Ligation of the cervix with ritodrine administration should be performed following admission to hospital, and EPH gestosis, anemia and IUGR should be carefully monitored. PMID- 1302426 TI - Within-pair similarity in MZ and DZ twins from birth to eighteen years of age. AB - This study is based on 145 pairs of twins included in a longitudinal study of a cohort of singletons born in 1953 and living in the Stockholm metropolitan area in 1963. Of these 145 pairs, 28 were classified as MZ, 103 as DZ and 14 pairs could not be classified. School achievement and ability test results have been collected for this group as well as data for the boys from physical and mental examinations on enrollment to military service. The purpose of this study was to compare within-pair similarity for MZ and DZ twins from birth onwards. There seems to be a divergent trend over time for MZ twin pairs to become more similar and DZ twin pairs to become less similar in height growth, school achievement and verbal ability. This is in accordance with previous research in this field. In relating similarity within pairs to birthweight, we found a drop in within-pair similarity for low birthweight MZ and DZ twin pairs (both twins < or = 2.500 g), but not for normal weight twin pairs. A discussion is initiated concerning methodological implications of these results. PMID- 1302427 TI - Twinning rates in Japan, 1951-1990. AB - Twinning rates in all of Japan for 1951-1968 and 1974-1990 were analyzed using data from vital statistics of Japan. The twinning rate per 1,000 births was 6.43 in 1951 and remained nearly constant until 1968, then decreased to 5.79 in 1974 and gradually increased to 7.00 in 1990. The MZ twinning rate increased slightly up to 1966, but decreased thereafter, whereas the DZ rate declined over the entire period. As for maternal age, the DZ rate increased up to the age group 35 39 and decreased thereafter. The same tendency is seen in the MZ rate, but the maternal age effect is less marked than in DZ twins. The same tendency is also seen in the overall rate for 1975-1985. As for geographical variations, the MZ and DZ rates were computed in each prefecture for 1955-1959 and in 1974. The DZ rate increased from a low level in the southwest Japan to a high level in the northeast for both periods, whereas the MZ rate was rather constant in 1974 throughout Japan. As for seasonal variation, the highest rates per 1,000 births for MZ(4.56) and DZ(2.20) twins were seen in April, with the lowest rate in September (3.69) for MZ twins and in July (1.71) for DZ twins. PMID- 1302428 TI - Intrapair differences of physical aging and longevity in identical twins. AB - The genetic and environmental contributions to physical aging (hair graying, balding, presbyopia) and longevity (age at death) were examined by within-pair comparison in monozygotic (MZ) and dizygotic (DZ) twins in later adulthood. Physical aging was investigated on 135 pairs of adult twins aged over 50. Hair graying and hair loss (baldness) showed significantly higher rates of concordance in the MZ twins than in the DZ twins. The intrapair difference of the degree of hair graying was negligible in 79%, slight in 15% and striking in 5% among the MZ pairs; while negligible in 40%, slight in 50% and striking in 10% among the DZ pairs. The intrapair difference of the degree of hair loss was negligible in 92%, slight in 8% (and striking in none) among the MZ pairs; while negligible in 69%, slight in 25% and striking in 6% among the DZ pairs. The age at onset of presbyopia showed a slightly higher rate of concordance in the MZ than in the DZ pairs. Longevity (age at death) was surveyed on 184 pairs of twins who died at over 40 years of age. The intrapair difference of longevity was 6.65 +/- 5.6 years (maximum 18.0; minimum 0.04) in the MZ pairs, and 8.66 +/- 7.2 years (maximum 18.6; minimum 2.9) in the DZ pairs. The MZ pairs showed a slightly smaller within-pair difference of longevity than the DZ pairs. PMID- 1302429 TI - Risk factors for cognitive aging in adult twins. AB - Monozygotic (MZ) and dizygotic (DZ) twins in later adulthood were studied in order to examine genetic and environmental contributions to the decline of cognitive performance. In this study, 118 twin pairs took a comprehensive medical examination at a university hospital. Cognitive function was measured by the Wechsler Adult Intelligence Scale (WAIS). The intraclass correlation coefficients on Digit Span (D) and Digit Symbol (DS) subtests of the WAIS did not show any significant difference between MZ and DZ twins although Block Design (BD) showed a significant difference. The values of the intraclass correlation coefficients were mostly around 0.5 and showed significant within-pair similarity of test scores. The mean score of D, DS and BD declined with advancing age. The intraclass correlation coefficients for D, DS and BD were around 0.2 in the MZ twins reared apart, and around 0.6 in the MZ twins reared together. These results indicated a significant environmental influence on cognitive aging in later adulthood. PMID- 1302430 TI - Perinatal mortality and prevalence of major congenital malformations of twins in Taipei city. AB - In order to examine perinatal mortality and prevalence of major congenital malformations in twins, deliveries in four teaching hospitals in Taipei City were studied. Among a total of 73,264 deliveries from October 1985 to June 1989, there were 844 pairs of twins. The zygosity of the twin pairs was determined by sex, placentation and 12 red blood cell antigens. There were 482 MZ and 252 DZ twin pairs identified, but the zygosity of a further 110 twin pairs was indeterminable due to lack of information on plancentation and/or blood types. A total of 4,573 singletons delivered in one study hospital from July 1986 to June 1987 were also studied as controls. The perinatal mortality rate was 7.5% for MZ twins, 1.4% for DZ twins, and 0.7% for singletons. The concordance rate of perinatal death was significantly higher in MZ (60%) than in DZ (0%) twins. The prevalence of major congenital malformations was 2.7% for MZ twins, 1.0% for DZ twins, and 0.6% for singletons. The concordance rate of major congenital malformations was 18% for MZ twins, but no DZ pair was concordant in any major congenital malformation. The concordance rate of facial clefts was 29% for MZ twins. There were 2 sets of conjoined twins giving a prevalence rate of 2.7 per 100,000 deliveries. These findings showing the prevalence of perinatal mortality and major congenital malformation to be highest in MZ twins, intermediate in DZ twins and lowest in singletons, suggest the importance of intrauterine environments in the determination of perinatal mortality and congenital malformations. PMID- 1302431 TI - Secular trend and associated factors of twinning in Taiwan. AB - Delivery records of public hospitals and local health centers were analyzed to investigate the secular trend of multiple births from 1955 to 1990 in Taiwan. Twinning rates decreased gradually from the late 1950s to 1973, slightly increased and remained stable from 1974 to 1980, and then increased strikingly from 1981 to 1990. During the study period, MZ rates were consistently higher than DZ rates except in 1986 when a higher DZ rate was observed. The highest MZ rate of 7.7 per 1,000 deliveries was observed in 1985, while the highest DZ rate of 4.6 per 1,000 deliveries was observed in 1986. The triplet incidence rate also declined from the early 1960s to 1973 and then increased markedly from 1974 to 1990. A case-control study including 482 MZ and 252 DZ twin pairs and 1,496 singletons was carried out in four teaching hospitals in Taipei City between October 1985 and June 1989 to examine factors related to twinning. The zygosity of twin pairs was determined by sex, placentation and red blood cell antigens. Multiple logistic regression analysis showed that the higher the maternal age, the lower the MZ and DZ rates, while the higher the parity, the higher the rates. There was no association of paternal age or of maternal educational level with twinning rates. PMID- 1302432 TI - Twins and genetic studies of man. PMID- 1302433 TI - Improvement of ocular blood flow with dopamine antagonists on ocular-hypertensive rabbit eyes. AB - The eyedrops of the ocular-hypotensive dopamine antagonists, trifluperidol, moperone, lenperone, and spiperone, were instilled into an ocular-hypertensive rabbit eye. The blood flows in the choroid, retina, iris root-ciliary body, and iris were measured with colored microspheres at various time periods. It was found that all these dopamine antagonists, at a concentration of 0.5%, increased the blood flow in all eye tissues. Dopamine, at a concentration of 3%, produced a biphasic action by decreasing the blood flow initially at 30 min, then increasing it at 120 min and thereafter. But 1.5% dopamine produced a monophasic action which increased the blood flow after 180 min. Since dopamine antagonists are not cholinergics or adrenolytics, they are not supposed to produce the side effects induced by pilocarpine or timolol. It is hoped that they can become satisfactory drugs for glaucoma and ocular hypertension. PMID- 1302434 TI - Induction of liver microsomal cytochrome P-450 2B1 by dimethyl diphenyl bicarboxylate in rats. AB - Dimethyl diphenyl bicarboxylate (dimethyl-4,4'-dimethyloxy-5,6,5',6'-dimethylene dioxy-di phe nyl-2,2'- bicarboxylate, DDB), a synthetic mimic of the natural product schizandrin C, is used in China as a hepatoprotective agent to improve the liver functions of patients with hepatitis or under cancer chemotherapy. In this study, we investigated the effects of DDB on liver microsomal drug metabolizing enzymes. When male Sprague-Dawley rats were treated with a daily intragastric dose of DDB (200 mg.kg-1) for 3 d, the microsomal pentoxyresorufin dealkylase activity and P-450 2B1 protein levels were markedly increased. The fold increase was lower than that by phenobarbital (75 mg.kg-1, ip once daily x 3 d). The level of P-450 2B1 mRNA was elevated by DDB but the magnitude of the elevation was much less than that caused by phenobarbital. DDB also increased the rates of testosterone hydroxylation at positions 16 beta, 16 alpha, 6 beta, and 2 beta as well as the rate of ethoxyresorufin dealkylation, suggesting moderate increases in the levels of P-450 3A and P-450 1A1 in addition to the huge increase in P-450 2B1. The level of glutathione S-transferase was also slightly increased, but the levels of P-450 2E1 and NAD(P)H: quinone oxidoreductase were not changed. The results indicate that DDB is an inducer of P-450 2B1. PMID- 1302435 TI - Effects of rifampicin on pharmacokinetics of isoniazid and its metabolite acetylhydrazine in rats. AB - After i.v. and i.p. injections of isoniazid (Iso) 40 mg.kg-1 to male Wistar rats, the plasma levels of Iso, acetylisoniazid (AcIso), and acetylhydrazine (AcHz) were determined by spectrophotometric method and gas chromatography. The results suggested that the pharmacokinetic behavior of Iso in rats belonged to a 2 compartment model. The plasma levels of AcHz in rifampicin (Rif 30 mg.kg-1) pretreated rats were lowered vs the control (P < 0.05 or < 0.01). The T1/2 of AcHz was shortened by Rif (control group 3.3 h, Rif-pretreated group 1.4 h) after i.v. injection of AcHz 10 mg.kg-1 to rats and the results showed that AcHz was converted to its active metabolites quickly by increasing the oxidative elimination rate of AcHz, which is related to the higher incidence of liver necrosis caused by Iso and Rif in combination. PMID- 1302436 TI - Effects of mebendazole, albendazole, and praziquantel on alkaline phosphatase, acid phosphatase, and adenosine triphosphatase of Echinococcus granulosus cysts harbored in mice. AB - Mice infected with protoscoleces of Echinococcus granulosus for 12-14 months were treated ig with mebendazole (Meb) 25-50 mg.kg-1 x d-1 for 7-14 d, albendazole (Alb) 200 mg.kg-1 x d-1, cr praziquantel (Pra) 500 mg.kg-1 x d-1 for 14 d. The mice were killed 24 h after the last medication, and acid phosphatase (ACP), alkaline phosphatase (AKP), and adenosine triphosphatase (ATPase) including (Na, K, Mg)-ATPase, (Na, K)-ATPase, and (Mg)-ATPase were determined and compared with those of untreated control group. The results showed that ACP activities of cyst wall in treated groups were lower than the control group. Whereas AKP activity of cyst wall in Pra group increased markedly, this is not the case in Meb and Alb groups. Three ATPase activities of cyst wall were inhibited in both Meb and Alb groups, Meb being more potent. No apparent changes in the ATPase activities were seen in Pra group. PMID- 1302437 TI - [Timed dose-response relationship analysis of pressor and hypotensive action of drugs]. AB - The graded and timed dose-response relationship (TDRR) of pressor and hypotensive action by i.v. norepinephrine (NE) and sodium nitroprusside (SNP) respectively were studied in 13 male rabbits. The arterial blood pressure was dose-dependently raised by NE 0.98-125 micrograms.kg-1 and lowered by SNP 7.81-500 micrograms.kg-1 (F test, P < 0.01). The comparisons between dose groups showed that the latency and duration of both NE and SNP action were dose-dependent (P < 0.01), and the data were nonlinear least-square fit to the hyperbolic 4-parameter model II (HFPM): Y = cs + 1/(magnitude of ln X - a)s + b, weighting the square error inversely with the square of Sx. In duration data, the regression equation was Y = 462.9906/(6.6924 - ln X) 0.9701 - 24.3335 for NE and Y = 374935.1632/(12.8573 - ln X)3.3975 - 3.139 for SNP action, while in latency, Y = 345.5548/(ln X + 7.8428)2.4056 + 3.9809 and Y = 17.9595/(ln X - 0.4898)0.5763 + 1.4768 for NE and SNP, respectively. Moreover, the positive correlation was found between the peak reaching time or average rising rate of the drug actions and the dose groups (P < 0.01). The results proved that the hyperbolic type of TDRR existed in the pressor and hypotensive action by iv drugs, and the HFPM was the common mathematical model to fit different TDRR data. PMID- 1302438 TI - [Effect of ketanserin on arterial baroreflex-blood pressure control in conscious hypertensive rats]. AB - The effect of ketanserin on arterial baroreflex-blood pressure control (ABR-BP) were studied in conscious freely-moving spontaneously hypertensive rats (SHR) and renovascular hypertensive rats (RVHR). The ABR-BP was measured by using a new method comparing with the pressor responses (in area) to angiotensin II before and after blocking the baroreflex efferent pathway by guanethidine and methyl atropine. It was found that ketanserin enhanced markedly the ABR-BP in both groups of hypertensive rats (SHR: 51% to 74%; RVHR: 59% to 77%). This suggests that the enhancement of ABR-BP may be involved in the anti-hypertensive effects of ketanserin. PMID- 1302439 TI - [Comparative effects of Panax notoginseng saponins, verapamil, and norepinephrine on cerebral circulation in anesthetized rats and rabbits]. AB - In urethane-anesthetized New Zealand rabbits, mean blood pressure (MBP) and cerebrovascular resistance (CVR) fell by 27-47% and 11-17% (P < 0.05), respectively after Panax notoginseng saponins (PNS) 20-80 mg.kg-1 i.v. Verapamil (Ver) 30 micrograms.kg-1 i.v. showed similar effects, but norepinephrine (NE) 30 micrograms.kg-1 i.v. showed opposite effects. PNS and Ver reduced the MBP and CVR in sodium pentobarbital-anesthetized Wistar rats. The actions of PNS and Ver on cerebral blood flow (CBF) were related to the animal species, i.e. PNS increased CBF in rats but reduced that in rabbits, Ver increased CBF in rabbits but had no effects on that in rats. In isolated ring segments of New Zealand rabbit basilar arteries, PNS 1 and 3 mg.ml-1 non-competitively inhibited the contractions induced by KCl with the pD2' value 2.69 +/- 0.20 (-lg g.ml-1). The results indicate that PNS and Ver are vasodilators of brain blood vessel, which would be beneficial to cerebral circulation, while NE is a vasoconstrictor of brain blood vessel. PMID- 1302440 TI - [Effects of tetramethylpyrazine on rabbit basilar artery ring and canine vertebroarterial circulation]. AB - Tetramethylpyrazine (TMP) inhibited the contraction of rabbit basilar artery and mesenteric arteries caused by KCl with an IC50 of 1.3 mmol.L-1 and 7.5 mmol.L-1 (P < 0.01). The contraction of the rabbit basilar and mesenteric artery ring evoked by KCl, CaCl2 and norepinephrine was inhibited noncompetitively by TMP with the pD2' values of 2.18 +/- 0.16 and 1.83 +/- 0.18 (P < 0.01), 2.13 +/- 0.12 and 2.08 +/- 0.12 (P > 0.05), 3.08 +/- 0.16 and 2.57 +/- 0.08 (P < 0.01), respectively. The contraction of rabbit basilar artery and saphenous veins evoked by 5-HT was also inhibited by TMP with an IC50 of 0.22 mmol.L-1 and 2.2 mmol.L-1 (P < 0.01), respectively. TMP antagonized the myogenic activity of rat portal vein strips. TMP increased canine vertebroarterial blood flow and had no effect on femoral artery blood pressure. The results suggested that TMP may block the calcium channel, inhibit the contraction of rabbit basilar artery, and improve the canine vertebroarterial circulation selectively. PMID- 1302441 TI - [Pharmacokinetics and pharmacodynamics of diltiazem floating tablets]. AB - Floating tablet is a new type of delayed-action preparations. The present study was aimed at pharmacokinetic and hemodynamic effects of diltiazem floating tablet in 8 healthy volunteers. Each subject received po 90 mg diltiazem floating and normal tablets in a crossover design. For floating tablets the T1/2 (6.4 +/- 4.4 h) and Cmax (56 +/- 23 ng.ml-1) were longer and lower than those of normal tablets (2.3 +/- 1.1 h and 96 +/- 30 ng.ml-1, P < 0.01), respectively. AUC of the 2 forms were similar, suggesting that they had same bioavailability. Diltiazem lowered the blood pressure of the subjects. Although there was no significant difference between the 2 formulations in maximal decreases of systolic and diastolic blood pressures, the duration of hypotension was longer with floating tablets than that with normal ones. There was a positive correlation between diltiazem concentration and its hypotensive action. Thus, administration of floating tablets twice a day may be effective in controlling the blood pressure of hypertensive patients. PMID- 1302442 TI - [Anti-lipid peroxidation and protective effects of phenytoin sodium on ischemic myocardium of mice]. AB - Isoproterenol (Iso, 20 mg.kg-1 x d-1 x 2 d) induced widespread and severe myocardial damages at ultrastructural level, decreased the myocardial Se glutathione peroxidase (Se-GSH-Px) and superoxide dismutase (SOD) activities, increased the serum creatine phosphokinase (CPK) concentration and myocardial malondialdehyde (MDA) content. Phenytoin sodium (Phe) 15 or 30 mg.kg-1 ip pretreatment diminished the CPK release and MDA production, protected the Se-GSH Px activity in the Iso-induced damage of mouse heart. The pretreatment with 30 mg.kg-1 abated the reduction of SOD activity. However, Phe 15 mg.kg-1 did not show such an effect. Phe (15 or 30 mg.kg-1) reduced the ultrastructural cardiotoxicity of Iso, and the membrane structure of ischemic myocardium was protected. The protective effects of verapamil pretreatment 3 mg.kg-1 ip were weaker than those of Phe on ultrastructural changes, but biochemical changes were similar to those of Phe. The results suggested that Phe possessed anti-lipid peroxidation and protective effects on ischemic myocardium. PMID- 1302443 TI - [Effects of Panax notoginseng saponins on monophasic action potentials of heart and automaticity and contractility of isolated atria]. AB - The effects of Panax notoginseng saponins (PNS) on monophasic action potentials (MAP) recorded from the myocardial surface by means of contact electrode were studied in 30 open-chest rabbits. The MAPA was increased and MAPD50, MAPD90 were prolonged with PNS (100, 200 mg.kg-1, iv), while the Vmax remained unchanged. PNS (300-1200 micrograms.ml-1) inhibited the automaticity of isolated guinea pig right atria and the contractility of the left atria. The positive inotropic action of ouabain (0.2 mumol.L-1) on isolated guinea pig left atria was decreased in the presence of PNS 300 micrograms.ml-1. PMID- 1302444 TI - [Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro]. AB - The cytotoxicities of 2 derivatives of artemisinin B and 2 derivatives of artemisic acid (designated as Compound A, B, C, and D) were investigated, using trypan blue dye exclusion test and colony-forming units assay. At the concentration of 5 micrograms.ml-1, the inhibition rates of these 4 compounds against murine leukemia cell line P388 were > 85%. When tested against human hepatoma cell line SMMC-7721 at 25 micrograms.ml-1, the inhibition rates of Compound A, B, C, and D were found to be 92.3%, 96.9%, 84%, and 82.1%, respectively, and 27%, 8%, 37.8%, 1.7% against normal human embryonic lung cell line WI-38, respectively. These 4 compounds all showed an inhibition rate of 100% against human gastric cancer cell line SGC-7901 at 50 micrograms.ml-1. PMID- 1302445 TI - [Pharmacokinetics of cytotoxin 14 from Naja naja atra venom]. AB - The pharmacokinetics of cytotoxin 14 (CT 14) from Naja naja atra venom was studied with biotin-avidin enzyme-linked immunosorbent assay. The plasma concentration-time curve of CT 14 after bolus i.v. 0.2 mg.kg-1 into rabbits was found to fit a two-compartment open model. T1/2 alpha was 5.8 +/- 0.6 min and T1/2 beta was 3.5 +/- 0.2 h. A rapid absorption was seen after im injection (0.5 mg.kg-1) to rabbits. The peak level was 260 +/- 90 ng.ml-1 and Tpeak was 13.6 +/- 2.4 min. The absolute bioavailability was 34 +/- 9%. It was shown that CT 14 was absorbed by gut. The peak level was 75 +/- 15 ng.ml-1 after a gastric gavage of 50 mg.kg-1 to rats. PMID- 1302446 TI - Drug prevention in a community setting: a longitudinal study of the relative effectiveness of a three-year primary prevention program in boys & girls clubs across the nation. AB - Tested the effectiveness of a youth drug prevention program in a community setting. Boys & Girls Clubs of America's Stay SMART program, adapted from a school-based personal and social competence drug prevention program, was offered, with and without a 2-year booster program, to 13-year-old members of Boys & Girls Clubs. Over 27 months, (a) 5 Boys & Girls Clubs offered the Stay SMART program, (b) 5 Boys & Girls Clubs offered the Stay SMART program with the booster programs, and (c) 4 Boys & Girls Clubs served as a control group. The Stay SMART program alone and the Stay SMART program with the booster programs showed effects for marijuana-related behavior, cigarette-related behavior, alcohol-related behavior, overall drug-related behavior, and knowledge concerning drug use. The Stay SMART program with the booster programs produced additional effects for alcohol attitudes and marijuana attitudes after each year of booster programs. Results suggest that a school-based personal and social competence program can be adapted effectively to a community setting and that booster programs might enhance program effects. Implications for alternative community models of prevention are discussed. PMID- 1302447 TI - Mental health status among Puerto Ricans, Mexican Americans, and non-Hispanic whites. AB - Compared mental health characteristics of island Puerto Ricans to three groups from the Los Angeles Epidemiologic Catchment Area Study: Mexican American immigrants, U.S.-born Mexican Americans, and Non-Hispanic whites. The Diagnostic Interview Schedule was used to obtain both diagnostic and symptom scale information about affective disorders, alcohol abuse/dependence, somatization, phobic disorder, and psychotic disorder. Mexican American immigrants had the fewest mental health problems of all groups. Puerto Ricans had more somatization disorder, but less affective and alcohol disorders than U.S.-born Mexican Americans or non-Hispanic whites. Results are considered in the light of selection factors, relative disadvantage of groups and methodological problems. PMID- 1302448 TI - The relationship between social support and maternal behaviors and attitudes: a meta-analytic review. AB - Used meta-analysis to analyze 66 studies that evaluated the relationship between social support available to the mother and maternal behaviors and attitudes. Investigators sampled relatively homogeneous populations of white, middle-class, married mothers of young children without physical or mental disabilities. A variety of instruments were used to assess key study variables. Significant correlations existed between both emotional and material support and maternal behaviors. Implications of these findings for funding of family support programs and for professionals working with mothers are discussed. PMID- 1302449 TI - Life stress, social support, and locus of control during early adolescence: interactive effects. AB - Examined the relationships between negative events, locus of control, social support, and psychological adjustment in an early adolescent sample. Of interest were the potential stress-buffering effects of social support and the conjunctive effects of social support and locus of control upon adjustment. Family support was positively related to adjustment in several domains, whereas school support was only related to school competence. Peer support was positively related to peer competence and anxiety, and negatively related to school competence. Examination of the buffering hypothesis suggested that both family and school support served to moderate the relationship between negative events and school competence. Conjunctive effects were also detected in that school support buffered number of negative events best for those individuals with an internal locus of control for successes. PMID- 1302450 TI - Residential and community treatment services utilized by a sample of youth with severe emotional disturbances. AB - Analyzed case records to determine the costs and service usage patterns for a group of 25 youth randomly selected from the case load of a regional mental health agency. Study participants had extensive histories of publicly supported psychiatric hospitalizations. An average of 36.2 contacts per youth (905 total contacts) with human services providers were documented. Approximately 2 out of every 5 contacts resulted in out-of-home placements. The estimated cost of providing services to the 25 youth exceeded 3 million dollars. The types and costs of treatment services provided to study participants are discussed. PMID- 1302451 TI - Determinants of hemodynamic results of balloon dilation of aortic recoarctation. AB - Between October 1982 and May 1990, balloon dilation of aortic recoarctation was attempted in 27 patients. In 1 case dilation was not performed owing to suspected aortic perforation. The remaining 26 patients had 30 procedures. The age at the first dilation ranged between 2.6 months and 18.3 years. After dilation, systolic gradient decreased from 49 +/- 17 mm Hg to 20 +/- 17 mm Hg (p less than 0.001). A reduction of gradient to less than or equal to 20 mm Hg occurred after the first dilation in 17 of 26 (65%) patients. Residual gradients between 25 and 80 mm Hg were present in the remaining 9 patients. During follow-up of 2 months to 6.7 years, 5 of 17 patients with a good initial result developed further recoarctation (2 had successful redilation, 2 had reoperation, and 1 is awaiting repeat dilation). Of 9 patients with gradients greater than 20 mm Hg after the first dilation, 1 had successful redilation and 3 had reoperation. The remaining 5 patients are being managed conservatively. 2 patients developed aneurysms after dilation (1 immediately and the other at 2 months). In all, 15 patients (58%) had a good, and 11 (42%) a poor late hemodynamic result. Aortic diameters at different levels of the aortic arch and at the reconstructed isthmus (normalized to the aorta at the level of the diaphragm) were significantly higher in the group with a good late result than in that with a poor one. Balloon/aortic diameter ratio at diaphragm level also had a significant influence on the late results. PMID- 1302452 TI - Haemolytic anaemia in a case of occupational asthma due to maleic anhydride. PMID- 1302453 TI - Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: increase in gradient after exercise. AB - To define alterations in the magnitude of the left ventricular outflow tract gradient during supine exercise, 10 patients with hypertrophic obstructive cardiomyopathy were studied under basal conditions and during exercise and recovery with simultaneous invasive hemodynamic measurements, particularly of the peak to peak systolic pressure gradient across the left ventricular outflow tract. Basal outflow pressure gradient ranged from 0 to 89 mm Hg (average 37.4 +/ 9.6). No increase was observed during 5 min of exercise (average 29.6 +/- 10 mm Hg, range 0 to 91; p = NS), even though arterial blood pressure, heart rate and cardiac index increased significantly in association with a decrease in peripheral vascular resistance. However, a rapid and highly significant increase in left ventricular outflow gradient occurred after exercise was completed (average 83.5 +/- 11.4 mm Hg, range 10 to 130; p less than 0.001), while arterial blood pressure, heart rate and cardiac index closely approached basal levels and total peripheral vascular resistance increased. In contrast to previous assumptions regarding the behavior of the outflow gradient in hypertrophic cardiomyopathy, obstruction to left ventricular outflow increases after rather than during supine exercise. Rapid changes in preload during recovery represent the most likely explanation for the postexercise development of outflow obstruction. New considerations regarding the mechanisms of sudden cardiac death and the therapeutic approach in patients with hypertrophic cardiomyopathy may result from this pathophysiologic observation. PMID- 1302454 TI - 'Needle-through-needle' technique for combined spinal-extradural anaesthesia in obstetrics. PMID- 1302455 TI - Breakage of an embolized intravascular catheter fragment: a complication of nonsurgical transvenous retrieval. AB - The use of permanently implantable central venous catheters may be complicated by catheter fracture and embolism. Nonsurgical retrieval of embolized catheter fragments is well established, and complications are rarely noted. We report a case in which the retrieval technique led to further fracture of a silicone rubber (Silastic) catheter and embolization to the lung. Silastic catheters may be prone to this complication, and appropriate caution during recovery of such catheter fragments is recommended. PMID- 1302456 TI - Is it practical to screen for familial vesicoureteral reflux within a private pediatric practice? AB - A prospective study was established within a private pediatric practice to identify the incidence and severity of vesicoureteral reflux in the siblings of patients known to have reflux. Twenty-four siblings of 18 children with reflux were studied. Eleven of these siblings were found to have reflux for an incidence of 46%. The risk of reflux in siblings of known children with reflux is thus significant and, at least in this study, compares with the risk of reflux after urinary tract infection. The outcome of the sibling group is discussed, along with our thoughts on the possible modes of inheritance of this disorder. PMID- 1302457 TI - Benign vaginal polyp: a histological, histochemical and immunohistochemical study of 20 polyps with comparison to normal vaginal subepithelial layer. AB - Twenty benign vaginal polyps from 18 patients, together with sections from normal vaginal epithelium, were studied histologically, histochemically using elastic van Gieson stain and immunohistochemically using monoclonal antibodies against vimentin, desmin and actin. The striking finding was the similarity, both histologically and immunohistochemically, of the stroma of vaginal polyps to that of the loose subepithelial layer found in normal vagina. The important difference was the marked degeneration of the elastic tissue, increased number of stellate and giant fibroblasts and subepithelial condensation of fibroblasts in the polyps. These findings support the hypothesis that vaginal polyps may represent a reactive hyperplasia of the loose subepithelial zone of the vaginal wall. PMID- 1302458 TI - Glaucoma filtering surgery with postoperative 5-fluorouracil in patients with intraocular inflammatory disease. AB - Twenty-one eyes of 18 patients with uncontrolled glaucoma and intraocular inflammatory disease had glaucoma filtering surgery with postoperative subconjunctival 5-fluorouracil (5-FU). Follow-up for eyes in which intraocular pressure was controlled ranged from 6 to 53 months (mean, 34 months; median, 35 months). Fifteen of 21 eyes (71%) had controlled intraocular pressure (21 mmHg or less). Control was achieved in 9 of 10 (90%) phakic eyes and in 6 of 11 (55%) aphakic or pseudophakic eyes with or without glaucoma medication. Four of six filter failures had a second filtering procedure with 5-FU, and of these four procedures, three were successful. Cataract progression occurred in 9 of 10 phakic eyes, leading to cataract surgery in 7 eyes. Other complications included corneal epithelial defects in 13 eyes, bleb leaks in 3 eyes, choroidal effusions in 13 eyes, 1 choroidal hemorrhage, 1 serous retinal detachment and macular retinal pigment epithelial disturbance associated with hypotony and choroidal effusion. Filtering surgery with postoperative subconjunctival 5-FU can successfully control intraocular pressure in eyes with ocular inflammatory disease. PMID- 1302459 TI - Predictive value of blood cultures. PMID- 1302460 TI - Hepatic dysfunction in Creutzfeldt-Jakob disease. PMID- 1302461 TI - Stereotactic localization mammography: interpreting the check film. AB - Stereotactic mammography is used to ensure accurate needle placement when localizing nonpalpable breast lesions. Once the localization needle is inserted into the breast, it is recommended that its position should be checked with a further stereo-image film. The interpretation of these check films can prove difficult. This paper describes how to detect and correct needle placement errors on check stereo-image films obtained during stereotactic localization procedures. The data presented relate directly to the CGR Stereotix and do not apply to the Siemens stereotactic equipment. The results are presented in a series of diagrams demonstrating the various types of errors in needle placement. Errors in needle depth produce particularly subtle signs. PMID- 1302462 TI - Subcutaneous T-cell lymphoma with florid granulomatous panniculitis. PMID- 1302463 TI - Epithelioid hemangioendothelioma of the liver: imaging findings with pathologic correlation. AB - Hepatic epithelioid hemangioendothelioma is a rare malignant neoplasm that has nonspecific clinical signs and symptoms and can be difficult to diagnose on the basis of biopsy results. Radiologists may suggest the diagnosis of this slowly progressive neoplasm by recognizing its characteristic radiologic features. We correlated images from CT (13), sonography (nine), and MR (six) with pathologic findings in resected whole livers (eight) and biopsy specimens (five) from 13 patients 25-58 years old. Gross pathologic examination showed a repetitive pattern of multiple solid tumor nodules, in a predominantly peripheral distribution, with coalescence as individual nodules exceeded 4 cm. Tumor nodules had a hyperemic rim. Lesions adjacent to the capsule often produced capsular retraction. These findings correlated well with imaging findings. On CT, the lesions were of low attenuation, peripherally based, and with capsular retraction or flattening in nine (69%) of 13 patients. Unenhanced CT scans showed superior conspicuity over contrast-enhanced CT scans (9/13, 69%) and showed the extent of lesions more accurately in all cases (13/13, 100%). In nine patients, lesions had a peripheral enhancement pattern of alternating attenuation values correlating with the hyperemic rim at pathologic evaluation. On sonograms, the tumors were solid and predominantly hypoechoic. On MR, tumor signal was low on T1-weighted and high on T2-weighted images, with a low-signal halo present around many of the lesions. CT, sonographic, or MR findings of coalescent peripheral hepatic masses with capsular retraction are highly suggestive of hepatic epithelioid hemangioendothelioma. PMID- 1302464 TI - Mechanical force, manually assisted short lever chiropractic adjustment. AB - OBJECTIVES: Chiropractic mechanical force, manually assisted short lever adjusting is a spinoff of the specific toggle recoil adjusting techniques, which were based on the original chiropractic subluxation theory propounded by Daniel David Palmer in 1895. This article reviews: a) the principles of the chiropractic subluxation complex from the standpoint of its historical origin and present-day scientific status; b) the purpose and objectives of specific spinal manipulative techniques; c) the use of mechanical adjusting instruments to effect a velocity/direction controlled adjustive thrust; and d) an assessment of scientific and clinical data relating to the biomechanical and neurological aspects of mechanical force, manually assisted short lever adjusting. DATA SOURCES: Prime sources were from the National Library of Medicine's on-line Index Medicus database, the Chirolars Research Resource Retrieval database, the Chiropractic Research Abstract Collection and the Chiropractic Library Consortium's reference works. Direct search of other nonindexed chiropractic sources was limited to those available in the collection of the National Institute of Chiropractic Research. Early information never documented by publication was obtained by written personal communication. STUDY SELECTION: The principal author selected articles reporting data (as opposed to anecdotal reports) from conference proceedings and peer-reviewed journals. DATA EXTRACTION: Data quality was assessed based on experimental conditions such as sample size, study design and statistical analysis. DATA SYNTHESIS: While mechanical force, manually assisted short lever adjusting seemingly is capable of beneficially altering the cause/effect relationship of spinal subluxations, more research in the nature of controlled clinical trials is needed to ascertain its benefits in the chiropractic treatment of specific conditions. CONCLUSIONS: Basic research is needed in order to establish the scientific basis for the chiropractic subluxation syndrome regardless of the technique employed. PMID- 1302465 TI - A better debonding procedure. PMID- 1302466 TI - The cranial base in subjects with dental and skeletal Class II. AB - The aim of this study was to test to what extent the cranial base variations may be involved in Class II facial organization. Using Bonferonni probabilities, cranial base size and shape, and facial divergence were compared in two groups: an experimental group of 45 subjects with dental and skeletal Class II and an homologous control group of 41 subjects with a natural Class I ideal occlusion. In all individuals of the experimental group the Class II molar relationship was at least equal to the width of one premolar and the ANB angle was greater than the value of the mean +2 standard deviations of the ANB in the control group. Spacing and crowding was less than 2 mm at each arch in both groups; all subjects were between 10 and 12 years old. The anterior part of the cranial base (SN length and SNBa angle) was identical in the two groups, but in Class II, cranial base flexure (BaSN angle) was more obtuse (P less than 0.05) and posterior cranial base angle (SBaN) was more acute (P less than 0.01). These variations co existed in the same group with a more retruded position of the condylar neck in the face (P less than 0.01) favouring per se a post-normal relationship of the mandible to the maxilla. The increased extension of the saddle angle in Class II could not be considered here as related to an hyperdivergent facial pattern since facial divergence was unchanged in Class II. Saddle angle and divergence correlated in Class I (r = 0.40; P less than 0.01), but not in Class II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302467 TI - Ode to Joy. PMID- 1302468 TI - Graduate medical education in the changing environment of medicine. PMID- 1302469 TI - Septic arthritis: a rare cause of drooping shoulder. AB - Drooping shoulder, or inferior subluxation of the glenohumeral joint, must be differentiated from true dislocation of the humeral head. In some instances, widening of the glenohumeral joint can be attributed to a large volume of intra articular fluid. Three patients with septic arthritis leading to drooping shoulder are described, representing the largest series with this development reported to date. PMID- 1302470 TI - Sickle cell vaso-occlusive pain crisis in adults: alternative strategies for management in the emergency department. AB - The gene for sickle cell disease is carried by 8% of the African-American population in the United States. The primary care physician is often called upon to recognize and treat one of the major sequelae of sickle cell disease--vaso occlusive pain crisis. An injectable nonsteroidal anti-inflammatory drug has recently become available and may offer some improvement in outcome of vaso occlusive pain crises. We present five case reports reviewing various current therapeutic options, including newer pharmacologic agents, and comment on alternatives to impatient management of pain crises. The use of the emergency department short-term observation unit as an alternative to hospitalization is discussed. PMID- 1302471 TI - A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. AB - OBJECTIVE: To evaluate critically Carl Wunderlich's axioms on clinical thermometry. DESIGN: Descriptive analysis of baseline oral temperature data from volunteers participating in Shigella vaccine trials conducted at the University of Maryland Center for Vaccine Development, Baltimore. SETTING: Inpatient clinical research unit. PARTICIPANTS: One hundred forty-eight healthy men and women aged 18 through 40 years. MAIN MEASUREMENTS: Oral temperatures were measured one to four times daily for 3 consecutive days using an electronic digital thermometer. RESULTS: Our findings conflicted with Wunderlich's in that 36.8 degrees C (98.2 degrees F) rather than 37.0 degrees C (98.6 degrees F) was the mean oral temperature of our subjects; 37.7 degrees C (99.9 degrees F) rather than 38.0 degrees C (100.4 degrees F) was the upper limit of the normal temperature range; maximum temperatures, like mean temperatures, varied with time of day; and men and women exhibited comparable thermal variability. Our data corroborated Wunderlich's in that mean temperature varied diurnally, with a 6 AM nadir, a 4 to 6 PM zenith, and a mean amplitude of variability of 0.5 degrees C (0.9 degrees F); women had slightly higher normal temperatures than men; and there was a trend toward higher temperatures among black than among white subjects. CONCLUSIONS: Thirty-seven degrees centigrade (98.6 degrees F) should be abandoned as a concept relevant to clinical thermometry; 37.2 degrees C (98.9 degrees F) in the early morning and 37.7 degrees C (99.9 degrees F) overall should be regarded as the upper limit of the normal oral temperature range in healthy adults aged 40 years or younger, and several of Wunderlich's other cherished dictums should be revised. PMID- 1302472 TI - Treatment of advanced squamous-cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. AB - BACKGROUND: For patients with advanced, unresectable squamous-cell carcinoma of the head and neck, radiotherapy is the standard treatment but has poor results. We therefore designed a randomized trial to determine whether alternating chemotherapy with radiotherapy would improve the survival of such patients. METHODS: Patients in the trial had biopsy-confirmed unresectable, previously untreated Stage III or IV, squamous-cell carcinoma of the oral cavity, pharynx, or larynx. They were randomly assigned to chemotherapy consisting of four cycles of intravenous cisplatin (20 mg per square meter of body-surface area per day for five consecutive days) and fluorouracil (200 mg per square meter per day for five consecutive days) alternating with radiotherapy in three two-week courses (20 Gy per course; 2 Gy per day, five days per week), or to radiotherapy alone (up to 70 Gy; 2 Gy per day, five days per week). RESULTS: The 80 patients given chemotherapy alternating with radiotherapy and the 77 given radiotherapy alone were comparable in terms of age, sex, performance status, disease stage, and site of the primary tumor. Complete responses were obtained in 42 percent of the patients in the combined-therapy group and 22 percent of those in the radiotherapy group (P = 0.037). The median survival was 16.5 months in the combined-therapy group and 11.7 months in the radiotherapy group (P less than 0.05); the 3-year survival was 41 percent and 23 percent, respectively. Severe mucositis occurred in 19 percent of the patients in the combined-therapy group and 18 percent of those in the radiotherapy group. CONCLUSIONS: In patients with advanced unresectable squamous-cell carcinoma of the head and neck, chemotherapy alternating with radiotherapy increases the median survival and doubles the probability of survival for three years as compared with radiotherapy alone. However, since local disease cannot be controlled in over half the patients who receive the combined treatment and since almost two thirds die within three years, further improvements in management are necessary. PMID- 1302473 TI - Incidence and other aspects of the epidemiology of schizophrenia in Denmark, 1971 87. AB - All Danish psychiatric patients admitted to hospital for the first time in the period 1969-88 with a diagnosis of schizophrenia given at least once during the period were included in the study. More than 8500 patients were examined in the Danish nationwide psychiatric register. First-admission rates decreased by approximately 50% irrespective of mode of calculation and increase in SMR. The use of in-patient care was unchanged despite a reduction in available beds of more than 40% in the study period. PMID- 1302474 TI - Treating before knowing. PMID- 1302475 TI - Shielding your patient from digitalis toxicity. PMID- 1302476 TI - Antenatal screening for Down's syndrome. PMID- 1302477 TI - New technology in U.S. Army health care: the role of laparoscopic cholecystectomy. AB - In the near future, laparoscopic cholecystectomy could become one of the most frequently performed surgical procedures in U.S. military hospitals. To determine the best way to implement this new technology in the U.S. Army Health Services Command (HSC), we have assessed the safety, efficacy, and health consequences of laparoscopic cholecystectomy. Approximately 2,800 open cholecystectomies are performed annually in HSC hospitals, 11% of them on active duty personnel. If cholecystectomies were performed using laparoscopic surgical techniques on active duty patients who meet currently accepted indications, 3,360 personnel duty days lost to convalescence and 7,048 days of limited duty (time on physical profiles) would be recouped. Applying the procedure to other beneficiaries (dependents and retired service members) would result in a potential annual savings of 11,000 hospital bed days. If implemented using stringent criteria for training and certification, these savings could be achieved with no increase in patient morbidity or mortality and with significant improvement in patient outcome. PMID- 1302478 TI - Infant mortality and army families: a case-control study. PMID- 1302479 TI - Balloon dilatation of heart valves. PMID- 1302480 TI - Is abuse a feminist issue? PMID- 1302481 TI - Growing medical income disparities threaten fee-for-service medicine. PMID- 1302482 TI - Renal failure after eating "magic" mushrooms. PMID- 1302483 TI - Perils of prediction in U.S./Canadian comparisons. PMID- 1302484 TI - Fourteen cases of imposed upper airway obstruction. PMID- 1302485 TI - Postprandial hyperlipemia does not inhibit platelet aggregation. PMID- 1302486 TI - "Neonatal i.v.s: practical tips". PMID- 1302487 TI - "Nurse/Physician relationships: getting things rolling". PMID- 1302488 TI - Comments on council report. PMID- 1302489 TI - Comments on council report. PMID- 1302490 TI - Vitamin A supplementation in malnourished Sudanese children. PMID- 1302491 TI - Causes of trauma in broilers arriving dead at poultry processing plants. AB - A post mortem examination was made on 1324 broiler carcases which arrived dead after being transported to six processing plants. The carcases were dissected and evaluated for trauma and obvious cause of death. Of the birds sent to the plants on the day of collection 0.19 per cent arrived dead and 35 per cent of these were thought to have died as a result of trauma. Haemorrhage associated with dislocation of the femur at the hip was the most common cause of trauma. Ruptured livers and crushed heads were other important traumatic injuries. PMID- 1302492 TI - [The reproductive potential of the bank vole (Clethrionomys glareolus Schreb) and of the tundra vole (Microtus oeconomus Pall.) under the conditions of the elevated radiation background of Bryansk Province]. AB - The continuous irradiation (connected with the accident on the Chernobyl atomic power plant) by cesium-137 of the dominant species of rodents (Clethrionomys glareolus, Microtus oeconomus) in the forests of Bryansk Province had a deteriorating effect on the state of reproductive organs and on the course of embryogenesis, stimulated the reproduction cycle but inhibited the rate of sexual maturation and increased the death-rate of young animals. These effects resulted in significant ageing of the population. But all these phenomena provoked by radiation are within the limits of rodents adaptive capacities. PMID- 1302493 TI - [The cardiosynchronous phenomena of the work of the brain: the psychophysiological aspects]. AB - The review is devoted to the heartbeat-related components of EEG and to the heartbeat-related oscillation of performance measures and the cortical evoked potentials. The studies of these phenomena are carried out within the Laceys' hypothesis elaboration as well as in the field of the exploration of visceral self-perception. The data obtained in these studies indicate that there are elements of the time-locking with heart rate, probably unrelated to cardiovascular regulation, in functioning of the highest brain structures. The problems in the interpretation of some of heartbeat-related phenomena of brain functioning and their possible participation in the mechanisms of the psychophysiological interaction are discussed. PMID- 1302494 TI - [The action of defoliants on the energetics of rat liver mitochondria in vitro]. AB - The effect of defoliants butyphos (I), dropp (II), butylcaptacs (III), hinazopin (IV), syhat (V), tetra-n-butylammonium bromide (VI), etrel (VII), gemetrel (VIII), allyl-4-methylpyridinium bromide (IX), 1-amino-cyclopropan-1-carbonate (ACPC) (X) at various concentrations (1 x 10(-5)-2 x 10(-4) M) on respiration, oxidative phosphorylation (OP) and permeability of the inner mitochondrial membrane from rat liver has been studied. It has been established that some of the compounds uncouple OP by increasing the inner mitochondrial membrane permeability for H+ (II) inhibit the respiration in V3 condition and induce less selective permeability for a number of ions (I, III). The other defoliants either induce respiration generally in metabolic states 3 and 4 (IV, VI, IX) or have no effect on the respiration and OP (V, VII, VIII, X). On the whole a good correlation between the common toxicity of the studied preparation (LD50) and their mitochondrial effect has been revealed, therefore the latter can be considered as intracellular "targets" involved in the realization of pesticide action. PMID- 1302495 TI - [The characteristics of lactate oxidation in the tissue mitochondria of rats of different ages]. AB - The parameters of respiration (V3, V4) and phosphorylation (the respiration control, ADP/O) have been studied using lactate as a substrate (obligatory with NAD addition) close by meaning to pyruvate on the liver and heart mitochondrion and homogenates of newborn rats. In 20-days and adult rats the mitochondria and homogenates oxidize the lactate (with NAD) with higher rate V4 but with lower value of respiration control as compared with the newborn animals. Simultaneously, a high activity of mitochondrial NADH-oxidase, oxidizing NADH, formed in the reaction of lactate dehydrogenase not connected with ATP synthesis. The role of mitochondrial NADH-oxidase are discussed as a factor increasing lactate oxidation, removing tissue lactate and activating the age dependent energy metabolism. PMID- 1302496 TI - [The biological indication of the radiation load in forest communities of small mammals]. AB - The content of cesium-137 in the organisms of different species of small mammals in forests of Bryansk Province five years later the Chernobyl accident varies to a great extent within some modal value n.10(-6)-n.10(-7) Cu/kg. Gamma-radiation is about 200 mcR/h. The revealed radiation level results in increased mortality during embryonal and postnatal periods, as during these periods a very intensive process of radiocesium accumulation in the animal organism takes place. Statistically valid differences of young and old animals ratio with the asymmetrical deviation towards old age groups have been found on the polluted territory at the end of summer season. PMID- 1302497 TI - [The mechanisms of the manifestation of the genotoxic effects of binase]. AB - The high concentrations of commercial sample of Bacillus intermedius 7P ribonuclease (binase) showed a weak mutagenic effect in Ames test and Ara-test. It has been established that binase induces the SOS-functions of microbial cell and prophage induction. The way of exogenic enzyme action through activation of RecA protein is proposed. PMID- 1302498 TI - [The effect of metal ions on the synthesis of extracellular enzymes by sporulating bacteria]. AB - The action of metal ions which are present in nutritious medium on the synthesis of extracellular enzymes by sporulating bacteria is analysed. An important role of these ions in post-secretory modification of protein molecules and formation of functionally active molecules of enzyme is shown. The effect of metal ions on some cell envelope properties and extracellular enzyme secretion is under discussion. PMID- 1302499 TI - [Alpha-glucosidase inhibitors of microbial origin]. AB - The data on spreading of inhibitors of alpha-glucosidases with microbial origin are given. Physiochemical characteristics of acorbose--a known inhibitor of alpha glucosidases--and new inhibitor isolated from Streptomyces sp. are given in detail. PMID- 1302500 TI - [Restriction endonucleases: the detection of new producer strains and the isolation of enzyme preparations]. AB - The method for analysis of microorganisms for the presence of the modification restriction systems has been developed. The method has permitted to detect more than 10 new producing strains of restrictases including microorganisms of Rhizobium genus. Some of them are promising for practical use. It has been shown that using selection of clones the strain productivity can be increased. The purification process for the majority of restrictases has been proposed. Some physical and catalytic properties of new enzymes have been studied. PMID- 1302501 TI - [Extracellular ribonuclease from Bacillus pumilus]. AB - The extracellular ribonuclease (RNAse Bp) was isolated from the cultural medium filtrate of Bacillus pumilus by ammonium sulfate precipitation and two stages of ion-exchange chromatography on carboxymethyl- and phospho-cellulose columns. The amino acid composition and N-terminal amino acid residue have been determined. The kinetic parameters of cleavage reaction of synthetic polynucleotides have been measured. According to their structural homology RNAse Bp has been shown to be similar to RNAses Ba and Bi. Catalytic properties of the enzyme are very close to RNAse Bi. PMID- 1302502 TI - [The cloning and expression of the RNAse structural gene of Bacillus intermedius]. AB - The structure gene of extracellular alkaline ribonuclease Bacillus intermedius (binase) has been cloned in E. coli cells in composition of pMT 316 plasmid carrying the inhibitor gene (barstar of barnase--binase structure homologue. The possibility to use such vector has been proved during the barstar action on binase catalytic activity. Using biochemical immunochemical analysis the expression of binase gene in E. coli cells has been confirmed. The recombinant clone E. coli which contains both plasmids simultaneously--carrying gene for barster and for benase has been produced. The given vector is suggested to be used for cloning of inhibitor gene to obtain a viable producer of alkaline intracellular ribonuclease. PMID- 1302503 TI - [The possible role of endogenous nucleases in the structural organization of chromatin]. AB - Two fractions of rat liver nuclei with different buoyant density have been obtained. The electrophoretic analysis of the oligonucleosome patterns of DNA out of nuclei of these two fractions revealed different levels of activity in endonucleases. In case of inhibition during the extraction of activity in Ca, Mg dependent endonucleases, the average size of high polymeric DNA is larger for nuclei with bigger buoyant density (fraction I) than for nuclei with smaller ones (fraction II). This finding is evidence of in situ existence of two pools of liver nuclei with different endogenic nuclease activities. In nuclear chromatin fraction I DNA is torsionally stressed; in fraction II it is relaxed that correlates with larger activity of endonucleases and smaller buoyant density of this fraction. A hypothesis on a possible role of endonucleases in chromatin structure organization has been put forward. According to this hypothesis a modulation of activity in nuclear endonucleases can determine different packaging and activity of chromatin from different pools of cellular nuclei. PMID- 1302504 TI - [The isolation of nucleases Sm1 and Sm2 in preparative amounts and a study of their antigenicity]. AB - Two enzyme forms of endonuclease (Sm 1 and Sm 2) strain B10M1 in 60 and 100 mg respectively have been isolated from the culture fluid Serratia marcescens. The chromatographic and electrophoretic properties and N-terminal amino acid residues are different for both enzymes. The purification procedure consists of dialysis and ion-exchange chromatography on DEAE- and phosphocellulose. The yield of nucleases Sm1 and Sm2 are 14% and 28% respectively. The antigenic differences of nucleases Sm1 and Sm2 have been found by cross immunoenzyme analysis. PMID- 1302505 TI - [The heat denaturation of bacterial ribonuclease studied by infrared spectroscopy]. AB - The thermal denaturation of bacterial ribonuclease in the interval of pH 2.5-7.0 has been investigated by means of infra-red spectroscopy method. The protein melting for pH 2.5 begins at the temperature 25 degrees C and is accompanied by secondary protein structure reconstruction, partially destroying native beta structure and leading to new denatured conformation appearance of different types of beta-turns. Spectral changes for pH 3.5 and 7.0 are significantly less in the same frequency areas. At the temperature more than 50 degrees C protein aggregation takes place with inter-molecule-beta-form formation. PMID- 1302506 TI - [New data on the potentials and prospects for the use of immobilized enzymes in medicine]. AB - The data on the completing level of a number of medical preparations on the basis of immobilized proteins, in particular, on the basis of enzymes are given. The firms and companies which successfully cooperate in the field of development of commercial programs for such preparations are listed. On the basis of own study a possibility to create some effective antitumor compounds in the next future is shown. The urgent and prospective application of the immobilized enzymes instead of the native ones in the medicine is grounded. PMID- 1302507 TI - [Nuclease conjugates with ligand-free serum albumin]. AB - In order to obtain nuclease and human serum albumin (HSA) conjugates with a high enzyme content it is proposed to use a ligand-free HSA. The ligands are removed with the help of a strong anion exchanger. A two-stage procedure of conjugate preparation is proposed. It consists in the complexation of ligand-free HSA and enzyme and subsequent co-condensation of protein molecules of the poly-complex with the aid of glutaric aldehyde. When the conjugates are administered to rabbits intravenously, the RNAase activity is manifested in blood for 3-5 days. Moreover, in the case of conjugates with a molecular weight of 80 kDa, the prolongation time is greater than for conjugate with a higher molecular weight. PMID- 1302508 TI - [The comparative characteristics of the biological and immunomodulating activities of enzyme preparations of microbial origin]. AB - A number of enzyme preparations of microbial origin such as immunomodulators and immunostimulators have been studied in vitro according to reactions of rosette technique of cell (ROC) active and general, adhesion, activation of a complement and also the spontaneous activity and phagocytosis of neutrophils have been determined. The enzyme preparations of microbial origin have been shown to be capable of causing immunomodulation and of influencing the specific and nonspecific immune response. Unlike the enzymes of animal origin the enzymes of microbial origin are effective in smaller concentrations. The studied preparations modulate the immune response differently according to ROC, adhesion. Each of preparations has specific features of biological activity--bacterio stationary in reaction to a certain group of microorganisms and some specific features of reaction with cell and levels of immune reactions. PMID- 1302509 TI - [The isolation of highly purified bacillary ribonucleases from recombinant strains of Escherichia coli]. AB - Active and inactive highly purified extracellular alkaline ribonucleases (barnase) from recombinant Escherichia coli have been prepared according to the industrial technology of Bacillus intermedius ribonuclease purification. Electrophoretic parameters and ultraviolet spectra characterize these preparations as homogeneous proteins. Immunochemical test system of identification of inactive RNAse for its purification has been worked out. PMID- 1302510 TI - [The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 1]. AB - The preparation of Hypericum perforatum L. has been shown to possess radioprotective properties. The effect found depends on the time of its taking and its concentration. A statistically reliable protection of marrow and the mucus of the thin intestine of mice from X-rays is observed. PMID- 1302511 TI - [The cytomorphological evaluation of the effect of Bacillus intermedius RNAse on the organs of experimental animals]. AB - Cytomorphological changes in organs of experimental animals after RNAse Bacillus intermedius treatment have been studied. It has been found that RNAse stimulates elements of lympho- and homopies of thymus and spleen and increases stromal reaction and functional activity of liver. The caused effects don't depend on catalytic enzyme activity. PMID- 1302512 TI - [The histological evaluation of the effect of Bacillus intermedius RNAse on the organs of immunogenesis in laboratory animals]. AB - Histological changes in organs of immunogenesis of experimental animals after RNAse Bacillus intermedius treatment have been studied. The effect of RNAse on organs is revealed in activation of both cell and humoral immunity and factors of nonspecific resistance at early stage of reaction. The inhibition of immunological reactions and factors of nonspecific resistance takes place at later stages of enzyme action. The caused effects don't depend on catalytic enzyme activity. PMID- 1302513 TI - [The antiviral action of a modified bacterial ribonuclease]. AB - The antiviral activity of a bacterial ribonuclease conjugate with chitosane of Kamchatka crab (in a form of water soluble chito-oligosaccharides) has been studied. The conjugate inhibitory activity for A and B viruses as well as to Sindbis arbovirus in tissue cultures is shown. The preparation efficiency at intramuscular and intranasal administration was observed at experimental influenza infection of white mice. PMID- 1302514 TI - [The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 2]. AB - The preparation Hypericum perforatum L. has been shown to decrease the intensity level of enzymatic and non-enzymatic processes of lipid peroxidation of rat liver microsomes in vitro and in vivo. In the mucus of the this intestine in vivo the increase of the number of non-enzymatic SH-groups is observed. Possible mechanisms of radioprotective action of the preparation is under discussion. PMID- 1302515 TI - [The effect of Bacillus intermedius RNAse on the multiplication of Candida tropicalis yeasts]. AB - The effect of Bacillus intermedius RNAse on the reproduction of Candida tropicalis and synthesis of the main biopolymers in the yeast cells. It has been found that stimulating action of the enzyme appears at the concentration of 10( 5)-10(-6) mg/ml and does not depend on the physiological state of the sowing culture. The connection between the increase of the ionic penetration and stimulation of the RNA and proteins synthesis in the yeast cells subjected to the RNAse action is shown. The mechanism of chromatine-associated RNA-polymerase activation is suggested to include the alteration of the ionic penetration of cells under the RNAse action. PMID- 1302516 TI - [The effect of sex steroid hormones on interhemispheric asymmetry in rats]. AB - The effect of gonadectomy and sex-steroid hormones treatment on functional interhemispheric asymmetry to the reaction of pain cry avoidance of another species (emotional reactions) and motor and exploratory activity of open-field behavior in Wistar rats of 3 months old has been investigated. A spreading depression technique for hemisphere inactivation has been used. The hemispheric asymmetry of the reactions in intact rats was characterized by sex dimorphism; the left hemisphere dominated to a great extent in males than in females under the control of emotional reactions; in motor and exploratory activity in open field behavior of rats the left hemisphere dominated in males and the right one- in female. In both sexes the neonatal gonadectomy levelled the interhemispheric differences in reactions under investigation. The following treatment of females with estradiol and males with testosterone didn't restore the asymmetry. After the castration at the age of 3 months the correlation between the size and direction of interhemispheric differences became reverse. The treatment of females with testosterone and males with estradiol both castrated in adulthood restored the interhemispheric asymmetry in males and had no effect in females. The treatment of intact rats with hormones of opposite sex led to the enhancement of left hemisphere dominance in motor and exploratory activity in males and levelled the asymmetry in females. It has been shown that in adult rats sex steroids effect predominantly the right hemisphere. PMID- 1302517 TI - [Development of the larvae inside the body of the itch mites Sarcoptes scabiei (L.) (Sarcoptidae) and the ontogenetic level of eclosion in mites of the order Acariformes]. AB - Several larvae-containing females of Sarcoptes have been found in skin biopsy of heavily infected Rangifer tarandas L. A. viviparity hypothesis is disproved. The larvae in the body of egg-containing dead females of the human Sarcoptes were obtained by incubation in the suspended water drop. Embryogenesis types as well as eclosion stage in Acariformes are discussed. The term "postmortal pregnancy" is proposed. PMID- 1302518 TI - [The effect of physicochemical environmental factors on the growth of gram positive bacterial dissociants]. AB - The growth of R-, S- and M (g)-dissociants of Streptococcus lactis, Bacillus coagulans, Rhodococcus rubropertinctus under the action of some physico-chemical factors: temperature, pH, ultraviolet (UV) rays, high concentration of NaCl and storage have been compared. R-variants gain selective advantage under the influence of UV-irradiation, high temperature and storage; S-variants--at decreasing of active pH of medium; M (g)-variants--at decreasing of growth temperature, high values of pH, increased NaCl concentration. The dissociation has been concluded to enlarge the limits of the species survival. PMID- 1302519 TI - [The genetic-demographic approach in anthropological research. XI. The structure of the reproductive behavior of Khakass families]. AB - A detailed analysis of chronological intervals typical of reproduction process has been carried out in rural Khakassian populations to reveal the mechanisms of natural selection and gene drift. It is shown that the process of reproduction is connected with cultural traditions and economical activity of a population under study. The main characteristics of reproductive family behavior (the whole number of children and sex ratio, birth interval ect.) play a very important role in family and kin relationships, age, sex and marriage-migration structure of the population. PMID- 1302520 TI - [The mechanisms of the porphyrin conformation of normal blood hemoglobin and in pathology]. AB - The spectra of resonance Raman scattering of blood in norm and under pathology (myocardial infarction and sepsis), as well after artificial hemotransfusion or UV photomodification have been studied. It has been shown that under heart pathology the structure of hemoglobin porphyrin macrocycle of erythrocytes changes, the size of porphyrin "nucleus" increases. The opposite conditions are observed at blood sepsis. It has been found that the traditional methods in tissue restoration, hemotransfusion and UV photomodification of blood don't result in complete restoration of hemoporphyrin molecule. PMID- 1302521 TI - [The intracellular pH of the peripheral blood lymphocytes in cattle during the development of leukemia]. AB - The intracellular pH distribution of peripheral cattle lymphocytes has been studied in normal state and at six stages of the development of bovine leukosis by the dye microfluorimetry of single cells. It has been shown that the increase of mean intracellular pH value occurs as well some distribution parameters, such as pH range and asymmetry change during the disease process. Probable reasons responsible for the observed modification of the distribution pattern are discussed. PMID- 1302522 TI - [The taxonomic status of the Tuva vole Alticola (A.) tuvinicus Ognev (Mammalia: Arvicolinae)]. AB - Some forms united under species Alticola tuvinicus s. lato (4 samples), A. semicanus (1 sample), A. argentatus (8 samples) are compared by 16 characters by means of principal component method and canonical analysis. Species distinctness of A. semicanus is confirmed. Specific status of the form olchonensis is supposed. The results concerning tuvinicus s. str. and kosogol are not clear-cut: these forms may be well differentiated subspecies within either A. tuvinicus s. lato or A. argentatus. PMID- 1302523 TI - [An ethological approach in the study of nonverbal communication in man and chimpanzee]. AB - The nonverbal communication of man and chimpanzee has been studied. Sexual dimorphism of nonverbal communication patterns, which is connected with the definite contexts of behavior are revealed. Possible ways of evolution in communication systems i shown. This analysis will permit to apply the data of ethological investigation of nonverbal behavior as sexual marker in diagnosis of different groups of mentally ill patients. PMID- 1302524 TI - [The effect of newly synthesized psychotropic preparations on the "open field" behavior of rats]. AB - The results of effect of some new synthesized psychotropic drugs of nootropic series on rats' behavior in "open field" are given. The increase of locomotive activity and decrease of emotional tension correlated with the rise of rats' ability to learning during working-out of avoidance reaction in shuttle-box, e.i. conditionally reflectory memory. It has been concluded that the study of dynamics of behavioral reactions in "open field" may be used for testing of new synthesized psychotropic drugs of nootropic series. PMID- 1302525 TI - [The biological action of chromium in relation to its valency]. AB - The biological action of chromium in the human or animal organism depends on valency: normal physiological activity is displayed at the expense of CrIII, but toxic activity is more characteristic of CrVI. In the digestive tract and pulmonary tissue CrVI may restore in CrIII. PMID- 1302526 TI - [The role of the hemopoiesis-inducing microenvironment in the mechanisms of the regeneration of hemopoiesis after cytostatic exposure]. AB - On the model of adriamycine-induced hemopoiesis hypoplasia it has been shown that the accelerated differentiation of hemopoietic precursors regeneration is of great importance in regeneration of hemopoiesis. This differentiation is provided by preceded recovery of bone marrow structural-functional organization. The important role in regeneration of hemopoiesis belongs to hemopoietic microenvironmental elements which express its induced influence by the increase of colony-stimulating and erythropoietic activities, interleukin-1 and interleukin-3 production. PMID- 1302527 TI - [The sexual behavior of the primates]. AB - The article presents the review of modern data of the field and laboratory investigations of primate sexual behavior, cyclicity, reproductive strategies and copulation in different primates taxa: strepsirrhini, platyrrhyni, catarrhini. The specific character, progressiveness and adaptation of some reproductive models are discussed by the authors. A problem of connection between dominance and reproductive success is also discussed, the role of sexual teaching in postnatal ontogenesis, age and hormonal status for expression of sexual behavior are analysed. Some forms of sexual declinations in primates are considered. PMID- 1302528 TI - [The clinico-biological aspects of transsexualism]. AB - A complex constitutional-endocrinological investigation of persons of both sexes with clinical diagnosis of transsexualism (TS) has been held. On the basis of original data some peculiarities of somato- and cerebrotypes of transsexuals have been revealed, the formation of these peculiarities is significantly connected with the action of sexual hormones. A disturbance in ratio of male and female sexual hormones in the direction of predominance of the hormones corresponding to the patient's sexual autoidentification despite their biological sex has been marked. It gives possibility to consider that TS pathogenesis is undoubtedly connected with inborn pathology of hormonal homeostasis. The results of multi disciplinary approach to study of TS are being discussed. An assumption about the role of disturbance in the system of "hormones-brain" in the TS origin is given. PMID- 1302529 TI - [Changes in the lipid component of thymocyte plasma membranes under the action of ionizing radiation]. PMID- 1302530 TI - [The immunomodulating properties of erythrocytes induced by physical factors]. AB - It is shown that the action of ultraviolet rays (UVR) or magnetic field (MF) on the erythrocytes of intact Wistar rats by weight 140-170 g induces the property to stimulate the immune response on sheep's T-dependent antigen-erythrocytes and on bull serum albumin in allogenic transference. The most expressed immune stimulated effect is induced by the heavy erythrocytes, which are effected by magnetic field. The warming and vibration don't induce the immunomodulating characteristics in erythrocytes. By spleen cells sticking to glass, the modified UVR and MF, the heavy erythrocytes induce factors (differentiated in mass), which stimulate the development of immune response to T-dependent antigens of sheep's erythrocytes and of bull serum albumin. These factors depress the function of antigen-specific T-suppressors and induce the immune-suppressive characteristics in light erythrocytes. PMID- 1302531 TI - [Response of human vascular endothelium to angiogenic fibroblast growth factor: role of 2 lipocortins/annexins]. AB - We are interested in whether lipocortins/annexins are involved in the response of human vascular endothelial cells (HUVEC) to angiogenic bFGF. Previously, a lipocortin/annexin of type I (p34) and a lipocortin/annexin of type VI were found to be associated with plasma membranes of HUVEC. Here we show that: i) phorbol ester PMA, a known activator of protein kinase C, possesses the property of acting synergistically with bFGF to stimulate DNA-primary initiation activity; ii) p69 is only detectable in membrane preparations from G1 phase HUVEC, whereas p34 is found to be present in membranes of G1 and S phase HUVEC; iii) the combination of bFGF and PMA induces an increased phosphorylation of p69 in late G1 phase. In contrast, phosphorylation of p34 occurs only in the S phase when HUVEC are treated with bFGF for an appreciable time lag (> or = 30 min) at 37 degrees C; iv)p69-enriched extracts from bFGF/PMA-treated HUVEC are found to be capable of enhancing the phospholipase A2 (PLA2)-catalyzed production of arachidonic acid in vitro; v) the DNA-synthetic response to bFGF plus PMA is consequent on stimulation of PLA2 and arachidonate production in late G1. These results suggest that p69 is directly connected to the mitogenic signal mechanism of bFGF in late G1, whereas p34 is associated with the endocytic process of this factor in S phase. PMID- 1302532 TI - [Contribution of expert systems in clinical practice: apropos of the Penelope experience, an expert system in assisted diagnosis and therapy of ovarian adenocarcinoma]. AB - An expert system (ES) for Diagnosis and Therapy of ovarian adenocarcinoma has been developed at the Institut Gustave-Roussy. From surgical and histological results, clinical examination and additional investigative reports, the system presents a synthesis and then determines the stage of the disease. The system than proposes therapeutic indications adapted to the characteristics of the illness and of the patient, and edits a report at the end of the ES consultation. This experience allowed us to specify the field of ES applications in oncology. As tools for diagnosis and therapy, they cannot act as a substitute for the know how of the physician, as too many medical decisions remain difficult to formalize in the ES. On the other hand the use of artificial intelligence techniques appears to be useful for establishing coherent data bases, which are necessary pre-requisites for clinical research in oncology. The integration of the system in the Hospital Information System is the guarantee of its use in current clinical practice. PMID- 1302533 TI - [Intra-alveolar hemorrhage during treatments of acute leukemia]. AB - Intra-alveolar haemorrhages represent frequent and severe complications in acute leukaemia treated with chemotherapy. Thrombocytopenia with or without associated haemostasis disorder in association with infectious or toxic lesions of the alveolar membrane (related to radio- or chemotherapy) represent the major promoting factors. Presence of intra-alveolar haemorrhage is mainly suspected on X-ray chest roentgenogram and can be confirmed by bronchoalveolar fluid examination demonstrating an excess of siderophages. Prevention of this complication is based upon reduction of risk factors. Platelet transfusions and careful introduction of steroids are proposed in certain cases. PMID- 1302534 TI - [Neoadjuvant chemotherapy and combined conservative treatment of soft tissue sarcoma in the adult]. AB - Between 1980 and 1990, 64 adults with a locally advanced soft tissue sarcoma, but without metastasis, were treated with neoadjuvant chemotherapy before conservative local treatment. Tumour localizations were limbs in 26 patients (40.6%) and other parts of the body in 38 patients (59.4%). Moreover, 27 patients had bone and/or vasculo-nervous axis involvement. Response to chemotherapy was > or = 50% for 23 patients (37.7%) with 3 complete remissions, < 50% for 36 patients and only 2 tumours progressed during chemotherapy. Conservative surgery was thus carried out for 51 patients (79.7%), 11 received external radiotherapy only. At the end of treatment, 49 patients (76.5%) were in complete remission. With a median follow-up of 76 months (range: 25 to 147), 25 patients are alive with no evolutive disease. For the whole population, the actuarial 5-year overall survival is 33.8%. Among the patients who were in complete remission at the end of therapy, 15 developed local recurrences (with metastasis for 7 patients) and 10 became metastatic. Actuarial 5-year overall survival for this subset of patients is 44.8%. PMID- 1302535 TI - Pattern of malignant lymphomas in Rwanda. AB - The pattern of 115 cases of malignant lymphomas diagnosed in the years 1979-1987 is presented using the updated Kiel's classification for non Hodgkin's lymphomas and after application of monoclonal antibodies L 26 and UCHL1 for the identification of B and T lymphocytes. Ninety-six cases (83.5%) were non Hodgkin's lymphomas and 19 cases (16.5%) Hodgkin's disease. Among non Hodgkin's lymphomas, B-cell lymphomas were predominant with a total number of 91 cases (94.8%). An analysis of B-cell lymphomas showed the following relevant features: a high frequency of lymphoplasmacytic/oid immunocytoma, a low frequency of Burkitt's lymphoma with a predominance of abdominal localisations, a high frequency of extranodal lymphomas (47.3%) and high grade lymphomas (48.4%); a 65% increase in high grade and extranodal lymphomas and a 76% increase in Burkitt's lymphomas and immunoblastic lymphomas in the period 1984-87 compared to the period 1979-83. For T-cell lymphomas, relevant features were the presence of one case of pleomorphic T-large cell lymphoma or adult T-cell leukemia-lymphoma and the fact that four out of five cases were large cell (high grade) lymphomas. More than 50% (57.9%) of Hodgkin's disease were of mixed cellularity type, only 15.8% being of nodular sclerosing type. The disease seemed to affect adolescents and young adults, more than 80% (83.3%) being aged 15-40 years. These features are compared to those observed by other authors and possible pathogenetic mechanisms are discussed. PMID- 1302536 TI - [Current epidemiology of cancers in Cameroon (Central Africa)]. AB - From 1986 to 1991, about 1,000 cases of cancers were diagnosed histologically every year in Cameroon. During this period, investigations showed that only 1 cancer out of 10 is diagnosed histologically. Thus, nearly 10,000 new cases of cancers are expected yearly in Cameroon where a population of 12,000,000 inhabitants is found leading to an incidence of about 100/100,000. Forty-nine percent of patients are female and 51% males. Twelve per cent of patients are less than 20 years old and 60% are between 40 and 70 years. Liver cancer is at the top of the list of cancers, representing 20%, followed by skin cancer (15%), breast cancer (11%) and cancer of the cervix (11%). For men, liver cancer is the most frequent, while cancers of the breast and uterine cervix predominate in women. PMID- 1302537 TI - [Retrospect and prospect on combined traditional and Western therapy in treating malignant tumours]. PMID- 1302538 TI - [Comprehensive "4-step analgesic ladder" therapy in treating cancer-related pain analysis of 486 cases]. AB - This analysis indicated that patients with cancer-related pain account for 71.0% in author's material. After the TCM treatment, the effective rate were 91.6% in hepatocarcinoma-related pain; 86.1% in colon-rectal cancer-related pain; 68.2% in malignant lymphoma-related pain; 100% in irradiation-related pain of esophageal cancer, lung cancer, post-operative breast cancer. Results of "four-step analgesic ladder" showed that 52.1% of pain could be relieved by Step I (TCM therapy); if Step II (indomethacin) or III (phenylbutazone) was added, the rate of pain relief reached as high as 96.5%; and only 3.5% need to be treated by Step IV (Opioids). With less side-effects and addiction of opioids and other narcotics, the "four-step analgesic ladder" therapy seems to be more suitable for cancer pain relief in China. PMID- 1302539 TI - [Clinical and experimental study on shen-qi injection with chemotherapy in the treatment of malignant tumor of digestive tract]. AB - Shen-Qi (Ginseng-Astragalus) injection was used with chemotherapy in the treatment of 176 cases of malignant tumor of the digestive tract. Results showed that Shen-Qi injection could reduce the toxic effects produced by chemical agents and increase the patient's body weight, as compared with that treated by chemotherapy alone (P < 0.001). It could protect the body's hematopoietic function. In Shen-Qi injection with chemotherapy group; the WBC count changed insignificantly but in chemotherapy group the WBC count reduced markedly, in which the rate of chemotherapy failure was 26.5% the difference between these two groups appeared to be significant (P < 0.01). Shen-Qi injection could increase the cellular immunologic function of the body, including phagocytic index and percentage of phagocytes, T lymphocyte transformation rate(cpm) as well as esterase stain. Further more, Shen-Qi injection could promote blood circulation to remove blood stasis and reduce the whole blood specific viscosity (P < 0.05). In the animal experiment, the total number of bone marrow cells and karyocytes of combined treatment group was found to be higher (P < 0.001) and the average weight of thymus was heavier (P < 0.05) than that in chemotherapy group. Shen-Qi injection could also prolong the survival time and increase the tumor inhibiting rate of experimental mice. PMID- 1302540 TI - [Histopathology of spleen deficiency syndrome of chronic atrophic gastritis and its ultrastructural changes]. AB - Pathologic change of gastric mucosa in 247 CAG patients of Spleen Qi (Yang) Deficiency (QYD) and Spleen-Stomach Yin Deficiency(YD) Syndrome were observed. The surface of gastric antrum mucosa of 26 patients with scanning electron microscope as well as the gastric mucosa of 34 patients with transmission electron microscope was observed for their intracellular structure. It was found that the CSAG and CAG I of Spleen QYD amounted to 165 cases (66.8%), and CAG II and III of Spleen-Stomach YD amounted to 34 cases (64.2%). It denoted that the Spleen QYD belonged to mild case, while the Spleen-Stomach YD belonged to severe case. The mitochondria of all kinds of gastric antrum mucosa cells showed retrograded degeneration, the pathologic basis of Spleen Deficiency of CAG, those of Spleen-Stomach QD had sparse broken and swollen mitochondria (82.3%), while the 53.3% of Spleen-Stomach YD displayed vacuolation as its predominant change. The different severity of retrograde degeneration and damage of mitochondria yielded various stage in atrophy of gastric mucosa which was the basis of Syndromes evolution from Defi. to QYD and then YD. Inflammatory change of the gastric mucosa was predominant in Spleen-Stomach YD (45.3%), and far less in QYD (27.1%), P < 0.01. PMID- 1302541 TI - [Treatment of chronic gastritis with traditional Chinese medicine--yingwei tablet]. AB - A prospective controlled study on the treatment of 60 cases chronic gastritis with TCM Yingwei tablet as well as Sucrafati and Doperidone tablets from Oct. 1990 to Sep. 1991 were done. 30 patients in each group. The cases in treated group took Yingwei tablet while that in control group took Sucrafati and Doperidone tablets. Before and after treatment, the patients were examined by gastroscope, pathology and Helicobacter pylori. The results showed that total effective rate, the gastroscopically effective rate, the pathological cure rate, the cure rate of gastric mucosa atrophy and the effective rate of bacteriocidal effect against Helicobacter pylori in treated group and control group was 96.7% and 73.3%; 80% and 70%; 36.7% and 20%; 38% and 9%; 60% and 23.0%, respectively, all of the above-mentioned differences between the two groups was significant (P < 0.05-0.01). Therefore Yingwei tablet is an effective drug for various kind of chronic gastritis. PMID- 1302542 TI - [Treatment of intestinal metaplasia and atypical hyperplasia of gastric mucosa with xiao wei yan powder]. AB - 138 cases of intestinal metaplasia (IM) and 104 cases of atypical hyperplasia (AH) of the gastric mucosa of chronic gastritis treated with Xiao Wei Yan Powder (XWYP) were reported. The diagnoses were based on the pathological examination of gastric antrum biopsy specimens. The cases were randomly divided into treated group and control group. The XWYP contained Smilax glabrae, Hedyotis diffusae, Taraxacum mongolicum, Caesalpinia sappan, Paeonia alba, Cyperus rotundus, Bletilla striata, Glycyrrhiza uralensis etc., and was prepared in powder form, taken orally 5-7g tid. After 2-4 months of administration, gastroscopic and pathological examinations were repeated. RESULTS: In treated group, the total effective rate of IM was 91.3% and that of the AH was 92.16%, while in control group, they were 21.3% and 14.46% respectively (P < 0.01). It denoated that XWYP had marked therapeutic effects for IM and AH. The animal experiments revealed no toxic effect, so safety guarantee was provided for its clinical application. PMID- 1302543 TI - [Treatment of esophageal precancerous lesion with cang dou pill]. AB - In this report, 648 cases of marked epithelium hyperplasia diagnosed with esophageal exfoliative cytology were studied clinically in the high incidence areas (Cixian and Shexian) of esophageal cancer. All these cases were randomly divided into the treated group and the control group. For two years, the former had been given Cang Dou Pill and the latter the placebo. The results reexamined by the cyto-smears showed that the incidence of the esophageal cancer in therapeutic and control group were 1.5% and 4.2% respectively. A significant difference existed between the two groups (P < 0.005). And the reverse rate of marked hyperplasia in the treated and control group were 79.5% and 50.2% respectively. There was significant difference between the two groups (P < 0.01). These results showed that Cang Dou Pill, to some extent, has anti-cancer activity. PMID- 1302544 TI - [Immunological and hematopoietic effect of Codonopsis pilosula on cancer patients during radiotherapy]. AB - Codonopsis pilosula was used as an adjuvant in 76 cancer patients during radiotherapy and its protective effect on hematopoietic and immunologic function was studied. RESULTS: (1) No influence on Hb and WBC of the patients with radiotherapy. (2) It could reduce the immunosuppressive effect of radiotherapy on delayed hypersensitive reaction, the lymphocyte response to PHA and IL-2. (3) No difference between treated and control groups in most humoral immune indices such as IgG, IgA and C3, but had slight increase in IgM in treated patients, while significant decrease in control. PMID- 1302545 TI - [Combined therapy of brain metastasis in lung cancer]. AB - 68 cases of brain metastasis in lung cancer were treated from June 1987 to Dec. 1990. They were randomly divided into 2 groups. The first group was solely treated by radiotherapy and the second one, by radiotherapy adding with the intravenous injection of the 10% Brucea javanica emulsion. The results showed that the living quality and the prolonged median survival of the patients in the second group (15 months) were much better than those in the first group (10 months). The 10% Brucea javanica emulsion has synergetic with radiotherapy in treating brain metastasis in lung cancer. PMID- 1302546 TI - [Fuzheng xiaoying therapy in treating 38 autoimmune thyroiditis patients]. PMID- 1302547 TI - [Anti-tumour study of combined therapy of yi kang ling with chemotherapeutic agents]. AB - Result of animal experiment proved that Yi Kang Ling, a TCM compound preparation, could markedly inhibit the growth of implanted tumour in mice. The inhibiting effect to the experimental tumour of combined therapy of Yi Kang Ling and the chemotherapeutic agents-CTX or MMC was better than that using singly. The Yi Kang Ling could alleviate toxicity of chemotherapy which caused the weight loss of mice. It could markedly increase the immune organs' weight, raise the phagocytosis of abdominal macrophage and promote the formation of serum hemolysin inhibited by CTX. The experimental result revealed that the combined therapy of Yi Kang Ling and the chemotherapeutical agents could enhance anti-tumour effect and lower the toxicity of chemotherapy. Toxicological experiment showed that the Yi Kang Ling did not have any toxic effect against organism. PMID- 1302548 TI - [Effect of yizhiling granule on experimental pathological model of Alzheimer's disease]. AB - Alzheimer's disease is an important problem of gerontology which manifested as serious loss of memory, especially of recent memory, decrease of brain weight. The pathological model of the disease in mice was made with administration of AlCl3 and then Yizhiling Granule was given to treat it. RESULTS: In the experiment of one trial passive avoidance response there were significant difference between the normal group and the model group (P < 0.01) and significant difference between the treated group and the model group (P < 0.05 0.01); as for fresh brain weight, the treated group was significantly different from the normal group (P < 0.01) and model group (P < 0.05). They indicate that Yizhiling Granule could improve memory and increase brain weight. This research seems to provide experimental basis for treatment of the disease. PMID- 1302549 TI - [Treatment of tumors and their progress by improving blood circulation to remove stasis]. PMID- 1302550 TI - [Progress on integrated traditional and Western medicine study of nasopharyngeal cancer]. PMID- 1302551 TI - [General survey on the literatures of "clinical treatise" in "Chinese Journal of Integrated Traditional and Western Medicine" collected in "Index Medicus" of USA, 1988-1990]. PMID- 1302552 TI - [1992 Proceedings report of the German Association for Otorhinolaryngology and Head and Neck Surgery. Part II meeting report. Garmisch-Parten Kirchen, 30 May 1992. Abstracts]. PMID- 1302553 TI - Joseph W. Cullen Memorial Award Lecture. Paving the road from basic research to policy: cigarette smoking as a prototype issue for cancer control science. PMID- 1302554 TI - A case-control study of breast cancer in Tianjin, China. AB - In a population-based case-control study of breast cancer in Tianjin, China, involving 300 cases and 300 population controls interviewed during 1985-1986, a number of strong risk factors were identified. Although average age at menarche was late by Western standards in this developing country (14.4 years), it was clearly related to risk. Women with their first menstrual period at age 12 years or earlier had 80% greater risk than women who started at age 17 years or later. Age at first full-term pregnancy was also strongly related to risk, with women whose first birth after age 30 years having 3.2 times the risk of women whose first birth was under age 20 years. Other established breast cancer risk factors in Western populations (family history of breast cancer, a history of benign breast disease, and use of oral contraceptives late in reproductive life) were also risk factors in this population. Parity and duration of lactation were both strongly protective against breast cancer development in univariate analyses. These two variables were highly correlated with each other and with age at first full-term pregnancy. Although the effects of each variable dissipated somewhat in multivariate analysis, our data strongly suggest that both parity and lactation independently contribute to breast cancer risk. PMID- 1302555 TI - Risk factors for oral and pharyngeal cancer in Shanghai, with emphasis on diet. AB - A population-based case-control study of oral and pharyngeal cancer was conducted in Shanghai, China, from 1988 to 1990, in which 204 (115 male, 89 female) incident cases and 414 (269 male, 145 female) controls were interviewed. Cigarette smoking and alcohol consumption, as well as occupational exposures to asbestos and to petroleum products and the use of kerosene stoves in cooking, were associated with increased risk of oral and pharyngeal cancer. In addition, more cases than controls reported having chronic oral diseases and false teeth. Dietary intakes of 42 major foods and selected salt-preserved or deep-fried foods during the past 10 years, ignoring any recent changes, were measured by a structured quantitative food questionnaire. After adjusting for known etiological factors, risks decreased with increasing intake of fruits, particularly oranges and tangerines, and some vegetables, including dark yellow vegetables and Chinese white radish. Men in the highest tertile of intake of these fruits and vegetables had about 30-50% the risk of those in the lowest tertile, with a less pronounced effect among women. A new finding was an excess risk associated with high consumption of salt-preserved meat and fish. The findings from this study provide further evidence that dietary factors play an important role in the development of oral and pharyngeal cancer. PMID- 1302556 TI - Antibodies to Helicobacter pylori and pepsinogen levels in children from Costa Rica: comparison of two areas with different risks for stomach cancer. AB - In children and adolescents from two areas of Costa Rica with contrasting gastric cancer risks, two factors suspected to be linked to the natural history of the disease were tested: serum antibodies to Helicobacter pylori and serum pepsinogen levels. One hundred fifty-five subjects from the high-risk area of Turrubares were compared to 127 from the low-risk area of Hojancha. No significant differences were found in the prevalence of IgG or IgA antibodies to Helicobacter pylori between the two regions. The prevalence of IgG was 65.8% in the high-risk area and 72.4 in the low-risk area, and that of IgA was 43% in both areas. The levels of pepsinogen, especially pepsinogen C, were significantly elevated in subjects with H. pylori antibodies in their serum. The mean levels of pepsinogen C in those negative, positive, and strong positive for H. pylori antibodies were 8.7, 14.3, and 21.1 ng/ml. These findings suggest that H. pylori-associated gastritis, predominantly of antral localization, is very prevalent in Costa Rican children and adolescents. Such gastritis might be associated with a high prevalence of intestinal metaplasia and a high gastric cancer risk in the inland, but not the coastal rural populations. H. pylori may therefore be an insufficient cause whose role in gastric carcinogenesis is contingent upon the presence of other factors. PMID- 1302557 TI - N-nitrosoproline excretion by rural Nebraskans drinking water of varied nitrate content. AB - The N-nitrosoproline (NPRO) test for in vivo nitrosation was applied in a study of 44 rural Nebraska men drinking high- or low-nitrate water from private wells. The subjects followed diets low in NPRO and nitrate for 5 days. On days 4 and 5 they avoided ascorbate-rich foods. Urine was collected for 24 h on day 4 while the subjects followed normal activities and on day 5 after an overnight fast and taking 500 mg L-proline. We determined NPRO, nitrate, creatinine, and specific gravity in the urines, and nitrite and nitrate in single saliva specimens collected on days 4 and 5. Results for all variables were separated into those above and below the median values and were analyzed by univariate and multivariate consideration of the contingency tables. Nitrate concentration in drinking water (> or = or < 10 ppm nitrate-nitrogen) was significantly associated with both day 4 and day 5 NPRO (> or = or < 1.5 micrograms/day; P < 0.04); and with urine nitrate (> or = or < 1.5 mmol/day), saliva nitrite (> or = or < 5 mg/liter), and saliva nitrate (> or = or < 25 mg/liter) (P < or = 0.002). Urine nitrate was significantly (P < or = 0.03) associated with both day 4 and day 5 NPRO, with odds ratios of 4.2 and 5.4, respectively. Creatinine was positively associated with NPRO on day 4 (P = 0.04). These findings, like those of a recent study in Denmark, showed an association between nitrate intake in water and NPRO formation. Their significance for people drinking high-nitrate water remains to be determined. PMID- 1302558 TI - Micronuclei in esophageal cells of Chinese youths in a high-incidence area for esophageal cancer in China. AB - An epidemiologic survey among 538 young persons between 15 and 26 years of age in a high-risk area for esophageal cancer in the People's Republic of China revealed a high prevalence of esophagitis. Histologically confirmed very mild, mild, and moderate esophagitis was observed in 31.6%, 10.7%, and 1.1% of 354 male and 30.4%, 4.3%, and 1.1% of 184 female subjects. The prevalence of micronuclei in esophageal smears was assayed in a subsample to investigate its possible association with esophagitis and with risk factors for esophageal lesions. Of the 186 subjects, 2.7% had mild or moderate esophagitis, 19.9% had very mild esophagitis, and 77.4% were normal. The frequency distribution of micronucleated cells in the esophageal mucosa was similar for the three diagnostic groups. Mean percentages of micronucleated cells did not differ by diagnosis of esophagitis, household status, current smoking status, presence of oral leukoplakia, or consumption of burning hot beverages or fresh fruit. Higher mean percentages were observed in the older age group of both sexes, but the difference was not statistically significant. The results suggest that if esophagitis is considered an important precursor state in the development of esophageal cancer, the scoring of micronuclei does not appear to be an efficient test for mild forms of esophagitis. PMID- 1302559 TI - Urinary type IV collagenase: elevated levels are associated with bladder transitional cell carcinoma. AB - Accumulating experimental evidence has linked the overproduction of extracellular matrix-degrading metalloproteinases with tumor cell invasion. In the present study one member of the metalloproteinase family, type IV collagenase (M(r) 72,000 gelatinase), is shown to be elevated in the urine of patients with transitional cell carcinoma of the bladder. The form of the enzyme in the urine was studied by three independent methods: enzyme-linked immunosorbent assay, Western immunoblotting; and gelatin zymography. Immunoblotting revealed that the enzyme was present as a series of fragments, each retaining the amino terminus of the mature proenzyme. A prominent M(r) 43,000 fragment was associated with the transitional cell carcinoma cases. Zymography demonstrated that multiple enzyme species with gelatinase activity were present in urine and that high-molecular weight bands of substrate lysis corresponded to complexes between type IV collagenase and tissue inhibitor of metalloproteinases 2. The total amount of type IV collagenase antigen was significantly elevated in the urine of 37 transitional cell carcinoma patients (range, 0-1081 ng/ml; mean, 318.4 +/- 147.3) compared to 19 normal controls (P < or = 0.004) and 17 inflammatory disease controls (P < or = 0.011). Immunohistochemical staining of bladder tumor biopsies verified that the transitional cell carcinoma cells were producing the M(r) 72,000 enzyme. Thus, M(r) 72,000 type IV collagenase, which is present in the urine in many forms including fragments and complexes with inhibitors, may be a useful marker for bladder cancer diagnosis or prognosis. PMID- 1302560 TI - Type IV collagenase/gelatinase (MMP-2) is not increased in plasma of patients with cancer. AB - We have developed a sensitive and specific sandwich-type enzyme-linked immunosorbent assay to detect M(r) 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] in human plasma. As a result of the linkage between MMP-2 production by cancer cells and the metastatic phenotype, we undertook this study to compare plasma MMP-2 levels in healthy individuals, patients with various types of cancer, and hospitalized patients with chronic diseases other than cancer. The results demonstrate that MMP-2 levels are not increased in cancer patients regardless of the extent of disseminated malignancy. In an effort to explain this data, we compared MMP-2 secretion by human umbilical vein endothelial cells and lung cancer cells passaged as cell lines. Endothelial cells secreted higher levels of MMP-2 than did lung cancer cells propagated in vitro. We propose that blood vessel lining cells make a sizable contribution to plasma levels of MMP-2 and may thereby obfuscate the detection of increased levels of MMP-2 originating from extravascular sources such as solid tumors. PMID- 1302561 TI - Allelic frequency of a p53 polymorphism in human lung cancer. AB - p53 is a tumor suppressor gene that is mutated in diverse tumor types. Here we report the frequencies of common polymorphic variants at codon 72 of the p53 gene in germline DNA of lung cancer cases and controls as determined by a polymerase chain reaction strategy. The observed allelic distribution was found to be significantly different between African-Americans and Caucasians in this U.S. population. The frequency of polymorphic variants was similar in lung cancer cases and controls after adjustment for race. However, among lung cancer patients the proline variant at codon 72 was in excess in adenocarcinoma patients by comparison with other histologies. PMID- 1302562 TI - Characteristics of women by smoking status in the San Francisco Bay Area. AB - To better understand why smokers are more likely to develop cervical cancer than nonsmokers, we investigated laboratory and demographic differences between the two groups. Women between the ages of 18 and 49 who attended eleven community clinics in the San Francisco Bay Area were studied to investigate differences between smokers and nonsmokers. The 332 smokers and 365 nonsmokers were queried about smoking habits, sexual and reproductive history, and recent diet. Cervical mucus specimens were cultured for yeast, lactobacillus, and other microorganisms. Results showed that white Hispanic women were less likely to smoke than white non Hispanic women. Smokers, when compared to nonsmokers, consumed larger quantities of coffee, soft drinks, liquor, and beer in the 24 h prior to the interview. Women who smoked were more likely than those who did not smoke to have had first sexual intercourse before age 16, had a greater number of lifetime sexual partners, and were more likely than nonsmokers to have been pregnant. After controlling for number of sexual partners, smokers reported a history of chlamydia, gonorrhea, and/or pelvic inflammatory disease more often than did nonsmokers, and cervical mucus of smokers was more likely than that from nonsmokers to contain greater than 8500 microorganisms/ml. PMID- 1302563 TI - Host factors in lung cancer risk: a review of interdisciplinary studies. AB - Host-specific factors influence risk for lung cancer. A few case-control and family studies of lung cancer susceptibility allowed for known lung cancer carcinogens and showed strong familial clustering with some evidence for a codominantly acting major gene. Cytochrome P-450 enzymes (e.g., CYP1A1) activate many carcinogens in tobacco smoke but have shown inconsistent associations with risk for lung cancer. Case-control studies that assess the effects of CYPIID6 on lung cancer risk have consistently shown a mildly decreased risk for lung cancer among poor metabolizers. Cell surface markers have shown little relation to risk for lung cancer. Studies involving DNA or hemoglobin adducts, sister chromatid exchange, or oncogene activation only indirectly measure host-specific risk, and these assays have suffered from poor reproducibility and high cost. We describe epidemiological designs to assess specific genetic factors that may alter lung cancer risk. PMID- 1302564 TI - A case-control study of the etiology of Ewing's sarcoma. AB - An interview case-control study was undertaken to search for risk factors for Ewing's sarcoma. The 208 cases, aged 5 months to 22 years at diagnosis and all white but one, were identified from hospitals participating in the Intergroup Ewing's Sarcoma Study therapeutic trials. Two controls were sought for each case: a sibling control and an age-matched regional population control identified through random-digit dialing telephone procedures. A questionnaire was administered to the parents of cases and controls. Parents were more likely to have smoked during the pregnancy with the case than during the pregnancy with the unaffected sibling. Risks rose with the number of cigarettes the mother smoked per day during the pregnancy. Concepti exposed to less than 1 pack/day were at 3.2 times the risk, and those exposed to 1 pack or more were at 6.7 times the risk of the nonexposed. However, risks associated with smoking were lower and not statistically significant in analyses using the region-matched controls. Hernias, mostly umbilical and inguinal, were diagnosed six times more frequently among the cases compared to region-matched controls. However, hernias occurred in just 10% of cases, and the matched siblings had hernias diagnosed with the same frequency as the cases. An apparent excess of heart disorders among cases versus siblings seems likely to be an artifact of increased medical surveillance of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302565 TI - Medical history and the risk of non-Hodgkin's lymphomas. AB - The relationship between selected aspects of medical history and the risk of non Hodgkin's lymphomas (NHLs) was investigated using data from a hospital-based case control study conducted in northern Italy on 177 cases of NHL and 561 controls in hospital for acute conditions, other than nonneoplastic or immunological. Among six viral diseases considered, only herpes zoster (shingles) had a relative risk (RR) significantly above unity [RR = 2.7; 95% confidence intervals (CI), 1.5 to 4.7]. The association, however, was restricted to subjects whose diagnosis of herpes zoster dated back to less than 10 years, suggesting that this slow-acting virus could be reactivated by the early development of NHL. Six of eight bacterial diseases considered showed RR above unity, and the estimate was significant for scarlet fever (RR = 1.9; 95% CI, 1.1 to 3.5) and pyelonephritis (RR = 5.3; 95% CI, 1.8 to 16.2). These associations were not restricted to the few years before lymphoma diagnosis. When various classes of infectious or inflammatory diseases were grouped together, no association was evident for viral infections (RR = 0.8; 95% CI, 0.6 to 1.2), acute bacterial diseases (RR = 1.0; 95% CI, 0.7 to 1.5), or allergic conditions (RR = 1.0; 95% CI, 0.6 to 2.1). The risk estimates were nonsignificantly above unity for chronic bacterial diseases (RR = 1.2; 95% CI, 0.7 to 1.2) and autoimmune conditions (RR = 1.4; 95% CI, 0.9 to 2.2), and significantly elevated for chronic inflammatory disease (RR = 1.9; 95% CI, 1.2 to 3.0).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302566 TI - Association of serum ferritin levels with the risk of stomach cancer. AB - A group of 5908 men provided serum samples during their study examination from 1967 to 1970. After a surveillance period of over 20 years, 121 incident cases of tissue-confirmed gastric cancer were identified. Their stored sera and those of 121 matched controls from the study population were tested for serum ferritin and transferrin levels. Because of the suggested effects of previous thawing on the serum results, detailed data analyses were limited to the 46 cases and matched controls whose sera were never thawed before this study. The mean serum levels (In ng/ml) were 5.26 for the 46 gastric cancer cases and 5.68 for their controls (P < 0.01). For serum transferrin, the mean levels (mg/dl) were 249.8 for cases and 254.1 for controls (P = 0.53). The inverse association with serum ferritin, which reflect total iron body stores, was stronger for the 21 cases diagnosed within 15 years of examination (P = 0.02) than for the 25 cases diagnosed after 15 years (P = 0.15). The limitations of the study and the implications of its findings are discussed. PMID- 1302567 TI - Immunohistochemical evidence of p53 overexpression in gastric epithelial dysplasia. AB - Molecular abnormalities of the p53 gene in chromosome 17p may be among the most commonly observed in human cancer. Their role in gastric carcinogenesis is suggested by their frequent detection in invasive adenocarcinomas. To investigate the chronology with which these abnormalities appear in the gastric carcinogenesis process, the expression of p53 proteins was investigated in late stages of the process, namely dysplasia, and in superficial carcinomas. A polyclonal antibody, CM-1, against both wild-type and mutant proteins was applied to paraffin-embedded biopsy and gastrectomy specimens previously fixed in buffered formalin. Positive nuclear stain was obtained in 36.4% of 33 cases of gastric epithelial dysplasia, corresponding to 19% of mild, 27.3% of moderate, and 64.3% of severe dysplasias. Eight of 13 (61.5%) invasive carcinomas showed positive stain. The data indicate an increased incidence of p53 abnormalities in the late stages of gastric carcinogenesis. PMID- 1302568 TI - Effects of breast cancer treatments on plasma nutrient levels: implications for epidemiological studies. AB - The interpretation of case-control studies in which blood nutrient levels are examined as etiological factors in cancer is complicated by the possibility that either the disease or its treatment may alter these levels. Circulating levels of selected nutrients were examined prior to diagnostic biopsy and compared with levels 3 to 4 months after diagnosis among 71 women with breast cancer and 95 women with benign breast disease. Among women with benign breast disease or women with breast cancer who were not given postsurgical adjuvant drug therapy, levels of alpha-carotene, lycopene, alpha-tocopherol, cholesterol, and triglycerides did not change over time. In contrast, women who received chemotherapy had increased levels of cholesterol, retinol, and alpha- and gamma-tocopherol, and women on antiestrogen therapy showed increased levels of triglycerides and alpha tocopherol. Overall, the concentrations of carotenoids (lycopene, alpha-carotene, and beta-carotene) did not change in breast cancer cases, although subgroup analyses showed increased levels of beta-carotene among cases not receiving drug treatment and decreased levels among those receiving antiestrogens. In summary, blood levels of some nutrients did not appear to be affected by breast cancer or its treatments, but changes were noted for levels of plasma lipids, tocopherols, retinol, and beta-carotene. Those investigating the etiological relationship between breast cancer and circulating nutrients need to consider these effects in designing and interpreting epidemiological studies. PMID- 1302569 TI - Urinary 6 beta-hydroxycortisol/cortisol ratios measured by high-performance liquid chromatography for use as a biomarker for the human cytochrome P-450 3A4. AB - Cortisol is metabolized to 6 beta-hydroxycortisol by the human cytochrome P-450 3A4, an enzyme implicated in the critical epoxidation reactions of aflatoxin B1 and certain polycyclic aromatic hydrocarbons. A method has been developed to measure the 6 beta-hydroxycortisol:cortisol ratio in human urine by reverse-phase high-performance liquid chromatography using diode-array detection. This method permits measurement of both cortisols in a single chromatographic run and has the potential to measure other metabolites useful for the determination of other human cytochrome P-450 activities. Using the 6 beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P-450 3A4 activity adjusts for the circadian fluctuation in cortisol levels, providing a determination that is consistent over a 24-h period, obviating the need for 24-h urine collections. This high performance liquid chromatography technique was used for the analysis of 14 different human urines and a range of ratios of 1.6 to 21.7 (mean +/- SE, 6.2 +/- 1.6) was found. These values are consistent with those reported in the literature. This method should be useful in molecular epidemiological studies investigating relationships between the susceptibility from environmental carcinogen exposure and cancer risk. PMID- 1302570 TI - A prospective study of hprt mutant and mutation frequencies in treated cancer patients. AB - We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1302571 TI - Impact of a physician intervention program to increase breast cancer screening. AB - In order to improve compliance with the National Cancer Institute's breast cancer screening guidelines, we developed a multifaceted intervention designed to alter physician screening practice. A pre-post test, two-community design was used. Primary care physicians in one community served as the control. Data were collected by two mailed surveys (1987 and 1990). Response rates were 61% and 64%, respectively. The physician intervention program consisted of a hospital-based continuing medical education program and an outreach component which focused on implementing a reminder system. Outcome measures were self-reported attitudinal, knowledge, and screening practices changes. In spite of an impressive change in comparison community physicians' practice, the difference in change over time in the intervention community physicians' ordering of annual mammography compared to the change in the comparison community physicians' ordering was significant (P = 0.04). The adjusted odds ratio is nearly 8. We conclude that our in-service continuing medical education program was successful in improving breast cancer screening practices among primary care physicians. PMID- 1302572 TI - Breast self-examination proficiency and training effects: women at increased risk of breast cancer. AB - While breast self-examination (BSE) frequency has received extensive research attention, proficiency has been less frequently addressed. Moreover, BSE proficiency among women at increased risk has not been adequately examined. Assessment of BSE proficiency is critical in determining the value of BSE with mammography and clinical breast examination in the early detection of breast cancer. BSE proficiency was assessed in 101 first-degree relatives of breast cancer patients. Participants were stratified by BSE frequency and randomized to one of two training techniques (MammaCare or concentric circle). BSE performance was assessed at baseline and at three follow-up visits at 4-month intervals. Proficiency was assessed by verbal description, a projected grid observational method, and lump detection ability on two breast models. BSE frequency was also assessed, in addition to BSE confidence, knowledge of breast cancer, risk perception, and worry related to breast cancer development. At baseline, proficiency was poor and correlations were not significant across assessment modalities. Significant improvement occurred on self-report measures, lump detection ability (true positives) on both models, and the projected grid. Improvement occurred across both training groups by the first follow-up, with no changes at subsequent visits. Both training techniques significantly improved BSE proficiency and were viewed positively by participants. PMID- 1302573 TI - Apoptosis in the genesis and prevention of cancer. AB - A strong rationale exists for developing cancer control strategies designed to suppress or reverse the development of precancerous lesions in order to reduce the occurrence and recurrence of this disease. Whereas numerous agents have been identified that inhibit tumor development, little is known about how they work. Recently the hypothesis has been raised that misregulation of apoptosis results in a failure of tissue size regulation that contributes to the development of cancer. If validated, this concept has important implications for the prevention of carcinogenesis and could lead to the development of new cancer control approaches that have as their basis the restoration of competence to regulate tissue size. Thus, it is essential to consider the role of cell loss in the tumorigenic process. In this regard investigation of the role of specific types of cell death in tumorigenesis, particularly the role of apoptotic cell death in maintenance of tissue homeostasis, has been neglected. The fact that apoptosis is a highly conserved, specific, and selective means of controlling tissue mass and shape also suggests that it can be exploited for the prevention or control of cancer. PMID- 1302574 TI - Correspondence re: A. R. Kristal et al., evaluation of a test for abnormal rectal mucus for early detection of colon cancer. Cancer epidemiol. biomarkers & prev., 1: 303-306, 1992. PMID- 1302575 TI - Correspondence re: A.R. Kristal et al., evaluation of a test for abnormal rectal mucus for early detection of colon cancer. Cancer Epidemiol., Biomarkers & Prev., 1: 303-306, 1992. PMID- 1302576 TI - Salt intake and stomach cancer: some contrary evidence. PMID- 1302577 TI - High-risk coronary angioplasty with percutaneous cardiopulmonary bypass support. PMID- 1302578 TI - High-risk coronary angioplasty using percutaneous cardiopulmonary bypass support. AB - BACKGROUND: Balloon angioplasty has a high success rate but results in abrupt closure of the vessel in 2% to 6% of patients. This can lead to haemodynamic collapse and death, particularly if the patient has poor left ventricular function. In the event of abrupt closure of the coronary vessels, such patients may not survive long enough to undergo emergency bypass surgery. The prophylactic use of cardiopulmonary bypass to support patients at high-risk for angioplasty has been reported recently. We describe our initial experience with this technique. METHODS: Eighteen high-risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high-risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < 25% in 13 patients). Triple-vessel disease was present in all of them. Angioplasty of the only remaining vessel was done in 12 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flow ranged from 2.8 to 4.5 litres and was discontinued after a mean of 35 minutes. Haemostasis was achieved by external clamp compression in 16 patients. RESULTS: The angioplasty was successfully performed in all the patients and was well tolerated. During the bypass period, the pulmonary artery diastolic pressure ranged from 0 to 8 mmHg. There was no hospital death. Two patients required surgical exploration of the femoral artery puncture site--one because of poor distal perfusion and the other for continued bleeding. During the follow up period of 1 to 10 months, 11 patients were free of angina and 1 had died. CONCLUSION: Our experience confirms that percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty is safe and effective. PMID- 1302579 TI - Impact of cigarette smoking on pulmonary function in non-allergic subjects. AB - BACKGROUND: Cigarette smokers have been shown to have a greater tendency to develop respiratory allergies than non-smokers. Since the early obstructive airway changes seen in respiratory allergy and smoking are similar, the early airway changes seen in populations of young smokers might be attributed to the fact that a proportion of smokers are allergic. We therefore studied the effects of smoking on non-allergic individuals. METHODS: Forced expiratory spirograms and peak expiratory flows were measured in a population of asymptomatic non-allergic male medical students, 59 smokers and 110 non-smokers. They had between 2 and 5 examinations performed serially over a period of 4 years. RESULTS: Smoking had a negative impact on pulmonary function. Analysis of covariance and multiple regression analysis using age, height gain and weight change as covariables showed that smokers, when compared to non-smokers, had a significantly greater percentage decline in the forced expiratory volume in one second expressed as a fraction of the forced vital capacity (4.01 +/- 4.6 v. 1.52 +/- 5.84), the forced expiratory flow in the middle half of the forced vital capacity (FEF25%-75%; 11.36 +/- 15.09 v. 5.3 +/- 17.58) and the ratio of the FEF25%-75% to the forced vital capacity (FEF/FVC; 14.06 +/- 14.45 v. 6.95 +/- 17.94). CONCLUSIONS: Our results suggest that young smokers, within a few years of starting to smoke, develop changes in pulmonary function indicating early peripheral airway narrowing, and that these effects worsen progressively with continued smoking. PMID- 1302580 TI - Single daily dose of carbimazole in the treatment of hyperthyroidism. AB - BACKGROUND: The antithyroid drugs, methimazole and carbimazole, are conventionally used in divided daily doses. However, these drugs have a longer intrathyroidal than a plasma half-life. We undertook this prospective, controlled study, in an area of mild iodine deficiency, to compare the efficacy of a single daily dose of carbimazole with divided doses in the treatment of hyperthyroidism. METHODS: Nineteen patients with hyperthyroidism received 30 mg of carbimazole daily at bed time (group A) while 14 received 10 mg of carbimazole every 8 hours (group B). These patients were assessed clinically and biochemically by estimation of serum total thyroxine, total triiodothyronine and thyrotropin before and 1, 2, 3, 4 and 6 weeks after treatment. RESULTS: There was no significant difference between mean baseline concentrations of thyroxine and triiodothyronine. After 1, 2, 3, 4 and 6 weeks there was a decline in their concentrations which was similar in both groups (p > 0.05). Euthyroidism was achieved in 4.6 +/- 1.4 weeks (range 2-6 weeks) in group A and in 3.8 +/- 1.2 weeks (range 3-6 weeks) in group B (p > 0.05). CONCLUSIONS: We conclude that carbimazole in a single daily dose is an effective method for treating hyperthyroidism in an area of mild iodine deficiency and its efficacy is comparable to divided dose therapy. This practical and acceptable method of treatment can be specially useful in patients who find it difficult to remember to take divided doses. PMID- 1302581 TI - Bacterial adherence to cotton and silk sutures. AB - BACKGROUND: Silk and cotton sutures are the most commonly used materials for skin closure, the choice being largely based on tradition. We undertook this study to compare the bacterial adherence in vitro to these two materials because it is well known that the physicochemical characteristics of a suture material influence its ability to attract bacteria and consequently promote wound infection. METHODS: We determined the bacterial adherence in vitro to cotton and silk for Staphylococcus aureus and Escherichia coli, common organisms found in postoperative infection at our institute, using three inoculum strengths. The sutures were incubated with the organisms and bacterial counts per suture material calculated after 20, 60, 120 and 180 hours of incubation. The bacterial counts for the sutures were then compared at these intervals. RESULTS: The bacterial adherence for both organisms at all time intervals was significantly greater to silk than to cotton, except at 60 hours for Staphylococcus aureus. The bacterial count for each suture material appeared to be an intrinsic property of the suture and did not vary with the concentration of the bacteria in the initial inoculum. The cost of an equivalent thickness of silk is 50 times that of cotton. CONCLUSION: We suggest that cotton should be the preferred suture for skin closure because bacterial adherence to it is lower and it is much cheaper than silk. PMID- 1302583 TI - 'Asian' doctors and discrimination in the United Kingdom. PMID- 1302582 TI - Molecular pathogenesis of chronic myelogenous leukaemia. AB - Chronic myelogenous leukaemia is a clonal neoplasm of the pluripotent haematopoietic stem cell which is characterized in most patients by a consistent cytogenetic abnormality known as the Philadelphia chromosome. This chromosome occurs as a consequence of a reciprocal translocation between the long arms of chromosomes 9 and 22 which results in the creation of a new gene comprising sequences from the c-abl gene on chromosome 9 and the bcr gene on chromosome 22. The protein encoded by this structurally altered hybrid gene differs from the normal c-abl gene product in both molecular weight and in tyrosine kinase activity. It is likely that these alterations in the c-abl gene product play a central role in the pathogenesis of this leukaemia. PMID- 1302584 TI - Interposed abdominal counterpulsation during cardiopulmonary resuscitation. PMID- 1302585 TI - Tuberculosis in children in India--I. PMID- 1302586 TI - A young male with anorexia, fever and jaundice. PMID- 1302587 TI - End stage renal disease--the end of the road. PMID- 1302588 TI - Medical colleges charging capitation fees. PMID- 1302589 TI - Who should judge medical competence? PMID- 1302590 TI - Impact of violence: physicians must face the epidemic. PMID- 1302591 TI - The biennial meeting of the International Association for the Study of the Liver, Brighton, UK, 6-8 June 1992. PMID- 1302592 TI - Indian medical journals. PMID- 1302593 TI - Regulating medical education. PMID- 1302594 TI - Victory of the people's movement against alcohol in Gadchiroli. PMID- 1302595 TI - Brain death and Justice Lentin. PMID- 1302596 TI - Hope for Indian science? PMID- 1302597 TI - Fraud in biomedical science. PMID- 1302598 TI - Environment and narcotics trafficking in Brazil. AB - This study of the State of Rondonia in Brazil sheds light on how and why the cultivation of illicit narcotics crops and drug trafficking are affecting non industrialized regions. It also highlights the negative impact of such activities on tropical ecosystems and human population. PMID- 1302599 TI - Environment and drug trafficking. AB - Illicit drug trafficking is a very complex matter, not only because it causes serious and pernicious problems in the socio-economic sphere, but because drug taking can lead to personal degradation. To this situation, lamentable enough in itself, must be added the immense ecological and environmental damage, which presents grave and serious dangers for the planet. PMID- 1302600 TI - Drug abuse control and the environment in northern Thailand. AB - The ecology in northern Thailand has been affected by the lifestyle of minority groups living there and some ethnic Thai people. Since 1970 development work to improve socioeconomic conditions and national security has been under way. The highlands cover an area of 17 million hectares consisting of forest and watershed areas. A new problem has arisen with the spread of heroin abuse in the neighbouring Lao People's Democratic Republic and Myanmar, producing a negative impact on the ecology, politics and the administration of minority groups. The Government of Thailand has shown flexibility in striving to solve these problems through development work in cooperation with the private sector. This has contributed to good relationships between the countries concerned. Some of the policies and programmes introduced by the Government of Thailand are reviewed in this article. PMID- 1302601 TI - Environmental impact of coca cultivation and cocaine production in the Amazon region of Peru. AB - Little or nothing has been written about the environmental consequences of the cultivation of coca and the production of basic cocaine paste. Nevertheless, there is much evidence that both activities have a severe and irreparable impact on the ecosystems in which they are carried out. This chapter describes the situation in the Peruvian Amazon, discusses the consequences of these activities, and recommends measures to improve current conditions. PMID- 1302602 TI - Illicit narcotics cultivation and processing: the ignored environmental drama. AB - Drug abuse and the environment are among the most preoccupying issues in today's world. Up to now, relatively little attention has been given to linkages between these two issues, which are at first glance unconnected in any meaningful way. More careful analysis identifies major linkages between the environmental impact of illicit drug cultivation, the rapid expansion of illicit cultivation into tropical forest areas, the efforts to eradicate illicit crops and pollution through the processing of raw materials into drugs of abuse. This article reviews those linkages and recommends measures that might be taken to deal with their consequences. PMID- 1302603 TI - La carte des microsatellites est arrivee! [The map of microsatellites has arrived!]. PMID- 1302604 TI - Centromeres--primary constrictions are primarily complicated. PMID- 1302605 TI - Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). AB - In the mammalian nervous system, serotonin (5-hydroxytryptamine) binds to distinct cell surface receptor subtypes that are defined by their ligand binding and effector-coupling properties. The 5HT1c receptor is a G-protein coupled receptor that stimulates phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, leading to the mobilization of intracellular calcium and to the activation of protein kinase C. By using somatic cell hybrid analysis and FISH, we have mapped the HTR1C locus to the human X chromosome, band q24 and to the mouse X chromosome region D-F4. Comparison of these map positions offers new insights into the evolution of human and murine X chromosomes. Since HTR1C is expressed in certain parts of the central nervous system and abnormal function of the serotoninergic system has been implicated in affective disorders, obsessive-compulsive disorder and epilepsy, establishing the precise map position of HTR1C is an important first step toward evaluating this locus as a candidate for mutations in these syndromes and in X-linked mental disorders. PMID- 1302606 TI - Structure and expression of the human pseudoautosomal gene XE7. AB - The human pseudoautosomal region comprises a 2.6 megabase segment of the distal short arms of the X and Y chromosomes. Complete DNA sequence homology between the two sex chromosomes is found in this region, and is believed to be important in mediating X-Y pairing in male meiosis. The only known functional genes in this region are MIC2 and CSF2R; in addition a pseudoautosomal location has been proposed for a genetic locus controlling stature. Here we report the structure of a recently identified pseudoautosomal gene, XE7, and its expression in human tissues. Analysis of genomic and cDNA clones shows that alternative RNA splicing results in the production of two predicted protein isoforms, one containing 385 amino acids and the other with 695 residues. The smaller polypeptide is a truncated version of the larger, and results from the inclusion of a cassette exon that introduces an in-frame stop codon into the mRNA. The XE7 gene appears to be ubiquitously expressed, and the production of both protein isoforms is predicted in each of several tissues examined. PMID- 1302607 TI - Cloning and characterization of an interstitial deletion at chromosome 11p15 in a sporadic breast cancer. AB - In a number of types of cancer including breast, hepatocellular, and bladder carcinoma, frequent losses of heterozygosity (LOH) on chromosome 11p15 have indicated the presence of one or more tumor suppressor genes in this region. In the present study, we report the detection and characterization of a rearrangement at 11p15 in a sporadic breast carcinoma. Genomic DNA clones encompassing the rearranged region were isolated; localization of both flanking clones to 11p15 by two-color fluorescent in situ hybridization (FISH) indicated that the rearrangement was caused by an interstitial deletion in the affected allele. Although it is uncertain whether the region between the flanking two loci was missing from tumor cells, our result implied that a putative tumor suppressor gene on chromosome 11p15 is located between the loci on either side of the interstitial deletion or may be interrupted by one of the breakpoints. PMID- 1302608 TI - Analysis of mutations at the neurofibromatosis 1 (NF1) locus. AB - A panel of 200 unrelated NF1 individuals has been screened for mutations using a panel of specific clones for the entire gene. DNA analysis on conventional Southern blots indicated that (20) 10% of NF1 patients showed aberrant bands. Small lesions involving nucleotide alterations were detected in a further 10 patients; 5 of these alterations have been fully characterised and are the novel mutations in the NF1 gene. A number of mutations were identified in exon 2. Identical mutations in this exon in two unrelated individuals involved an insertion of cytosine into codon 5662 and resulted in an inappropriate stop codon. This mutation also created a new MnlI site. Another novel mutation in exon 2 resulted from the insertion of thymidine at nucleotide 5678, which also created an inappropriate stop codon. We have so far completed the screen of exons 1-9 of the NF1 gene for the identification of mutations and have found no evidence of clustering of such mutations in the gene. PMID- 1302609 TI - Microdissection of a human marker chromosome reveals its origin and a new family of centromeric repetitive DNA. AB - A series of procedures including chromosome microdissection, sequence-independent PCR, Southern-blot-hybrid-selection-cloning and sequencing of microdissected DNA library members were used to analyze DNA from a familial marker chromosome centromere and to determine the origin of the marker chromosome in the case of a live-born, tetraploid human infant. A new family of repetitive DNA, termed sn5 satellite, was sequenced and characterized by DNA hybridization. The sn5 satellite family appears to be primate-specific and shows a chromosome-specific distribution which parallels that of alpha satellite suprachromosomal family 2. This suprachromosomal classification is based on sequence similarity of centromeric alpha satellite DNA within particular groups of chromosomes. It has been postulated that the similarity of alphoid sequences within each of the three suprachromosomal families results from homologous exchanges between nonhomologous chromosomes within each family. The parallel distribution of sn5 satellite sequences at the centromeres of chromosomes of alphoid suprachromosomal family 2 suggests that homologous exchanges between non-homologous chromosomes may be the basis of simultaneous chromosome-specific sequence conservation for multiple centromeric satellite DNA families. PMID- 1302610 TI - Lambda CM8, a human sequence with putative centromeric function, does not map to the centromere but is present in one to two copies at 9qter. AB - A DNA fragment isolated from a human genomic library, was reported to be present at all human centromeres and present at 16-32 copies per genome. Reintroduction of this DNA into mammalian cells as a concatenated phage clone gave rise to dicentric chromosomes which gave rise to a new, stable, chromosome. Taken together these observations could mean that this DNA is part of a native centromere. We have reexamined the location and copy number of this sequence and find it to be present at 1-2 copies per genome with a single site of in situ hybridisation at 9qter. PMID- 1302611 TI - The putative centromere-forming sequence lambda CM8 is a single copy sequence and is not a component of most human centromeres. PMID- 1302612 TI - A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes each with a second novel mutation. AB - Three novel Tay--Sachs Disease (TSD) mutations have been identified in two unrelated, non-Jewish compound heterozygous patients. A G772C transversion mutation causing an Asp258His substitution is shared by both patients. The mutant enzyme had been characterized, on the basis of previous kinetic studies (1) as a B1, or alpha-subunit active site mutation. This is the first B1 mutation not found in codon 178 (exon 5). A C508T transition causing an Arg170Trp substitution also occurred in one of the patients. The third mutation is a two base deletion occurring in exon 8 involving the loss of either nts 927-928 or 929-930 in codon 310. The deletion creates an inframe termination codon 35 bases downstream. The Arg170Trp mutation was also detected in a third unrelated TSD patient. In both families this allele was traced to French Canadian ancestors originating in the Estrie region of the province of Quebec. This mutation is the third TSD allele unique to the French Canadian population and the ancestral origins of the carrier parents are distant from the center of diffusion of the more common 7.6 kb deletion mutation which is in the eastern part of the province. PMID- 1302613 TI - A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. PMID- 1302614 TI - Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family. PMID- 1302615 TI - Four dinucleotide repeat polymorphisms on human chromosome 16 at D16S289, D16S318, D16S319 and D16S320. PMID- 1302616 TI - A highly polymorphic polypurine sequence on chromosome 8 (D8S210). PMID- 1302617 TI - CGG repeat polymorphism at the c-Ha-ras oncogene locus. PMID- 1302618 TI - Two dinucleotide repeat polymorphisms at the DXS571 locus. PMID- 1302619 TI - Dinucleotide repeat polymorphisms at the D10S183 and D10S245 loci. PMID- 1302620 TI - Dinucleotide repeat polymorphism at the DXS559 locus. PMID- 1302621 TI - Dinucleotide repeat polymorphism at the D18S74E locus. PMID- 1302622 TI - Tetranucleotide repeat polymorphism at the human alpha fibrinogen locus (FGA). PMID- 1302623 TI - Dinucleotide repeat polymorphism in the promoter region of the human von Willebrand factor gene (vWF gene). PMID- 1302624 TI - Polymorphic dinucleotide repeat in a cartilage matrix protein (CRTM) gene. PMID- 1302625 TI - An informative microsatellite repeat polymorphism in the human neurofilament light polypeptide (NEFL) gene. PMID- 1302626 TI - PCR detection of a dinucleotide repeat in the human histidine-rich glycoprotein (HRG) gene. PMID- 1302627 TI - A common EcoRI polymorphism at the ZFX locus. PMID- 1302628 TI - A Brassica napus transcript encoding a protein related to the Kunitz protease inhibitor family accumulates upon water stress in leaves, not in seeds. AB - A cDNA clone encoding a Brassica napus drought-induced 22 kDa (BnD22) protein has been isolated and characterized. The BnD22 transcript accumulated in response to drought reversibly, and to other conditions of leaf water deficit such as rapid water stress or salt acclimation, but not to cold acclimation or heat shock. Exogenously applied abscisic acid induced both changes in leaf morphology similar to the drought-adaptive response and a pronounced accumulation of the BnD22 mRNA. In control and drought-adapted plants, the BnD22 transcript was expressed in an organ-specific manner: the mRNA level was highest in leaves, low in hypocotyls and undetectable in roots. Sequence analysis indicates that the BnD22 protein is related to the Kunitz family of protease inhibitors. In contrast to most members of this family, and also to most polypeptides expressed in vegetative tissues upon drought, the BnD22 mRNA was absent in seeds, before or during the seed desiccation phase. The BnD22 gene represents a new class of genes which are strictly induced in vegetative tissues upon environmental stress, and its pattern of expression shows that the responses to water deficit differ, at least partially, in seeds and in leaves. PMID- 1302629 TI - Characterization of a pollen-specific cDNA from sunflower encoding a zinc finger protein. AB - We have isolated, via differential hybridization screening of a floral cDNA library from sunflower, a cDNA clone that hybridizes to a 1100 nucleotide-long mRNA found exclusively in mature pollen grains. The cDNA encodes a 219 amino acid long polypeptide containing two potential zinc fingers alternating with two basic domains. A similar organization is found in the erythroid-specific transcription factor Eryf1 from chicken and its murine homolog GF-1. The C-terminus of the protein contains a sixfold repeat of the pentapeptide sequence (S,T,A)(E,D)TQN. These features suggest that the SF3 protein is a transcription factor required for the expression of late pollen genes. The SF3 gene is a member of a multicopy gene family. A genomic copy of the gene has been isolated and sequenced; it is split by four short, AT-rich introns. PMID- 1302630 TI - The ptl1 gene expressed in the transmitting tissue of Antirrhinum encodes an extensin-like protein. AB - ptl1, a gene expressed specifically in pistil transmitting tissue of Antirrhinum flowers, encodes a protein with similarity to plant extensins. The protein is rich in proline (28%) and serine (9%) and contains several proline-rich repetitive amino acid motifs found in other extensin-like proteins. The presence of three consensus N-glycosylation sites indicates that it is probably glycosylated. RNA blots show that the ptl1 transcript is abundant in mature pistillar tissue but absent from immature flower buds and all other plant organs tested. In-situ localization of mRNA demonstrates that ptl1 expression is confined to the transmitting tissue of the style and stigma. The presence of a putative signal peptide at the N-terminus of the protein, taken together with the expression pattern, indicates that the ptl1 product may be secreted into the extracellular matrix of the transmitting tissue. The possible contributions of the ptl1 product to the physical properties of the transmitting tissue are considered in the light of current views on extensin structure and function. PMID- 1302631 TI - The adenine nucleotide translocator of higher plants is synthesized as a large precursor that is processed upon import into mitochondria. AB - Two maize genes and cDNAs encoding the mitochondrial adenine nucleotide translocator (ANT), a nuclear-encoded inner mitochondrial membrane carrier protein, have previously been isolated in this laboratory. Sequence analysis revealed the existence of much longer open reading frames than the corresponding fungal and mammalian ANT genes. Potato ANT cDNAs have subsequently been isolated and sequenced and alignment of the deduced plant amino acid sequences with the equivalent fungal and mammalian polypeptides indicated that the plant proteins contain N-terminal extensions. When the plant cDNA clones are expressed in vitro they direct the synthesis of precursor proteins that are specifically processed at the N-terminus upon import into isolated mitochondria. N-terminal amino acid sequence data obtained from the native proteins purified from both maize and potato mitochondria has allowed identification of the putative processing sites. Further import analysis has shown that two distinct regions of the maize precursor protein contain targeting information, the 97 amino acids at the N terminus and the 267 C-terminal amino acids. This is the first report that provides experimental evidence that the adenine nucleotide translocator of higher plants is synthesized as a large precursor protein that is specifically cleaved upon import into mitochondria. Import of ANT into higher plant mitochondria therefore appears to be different to the corresponding process in fungal and mammalian systems where targeting of ANT to mitochondria is mediated by internal signals and there is no N-terminal processing. PMID- 1302632 TI - Molecular analyses of a barley multigene family homologous to the yeast protein kinase gene SNF1. AB - Genomic sequences homologous to the yeast gene SNF1 have been isolated from barley (Hordeum vulgare) cv. Sunbar. SNF1 encodes a protein serine/threonine kinase required for the derepression of a number of genes, including SUC2 (invertase) in response to glucose deprivation. Southern blotting showed the presence of a family of related genes in barley and full-length sequences have been determined for two members of the family, one of which lacks an exon and is almost certainly non-functional. A partial sequence has been obtained for a third member of the family. The transcription start site of one of the genes has been determined by S1 nuclease protection. A transcript almost identical in sequence to the exons of one of the genes has been amplified from barley endosperm mRNA using the polymerase chain reaction. One of the full-length genomic sequences contains nine introns and 10 exons and the number and position of the introns in the second full-length sequence is identical except that it lacks exon 2. However, the length and sequence of the introns vary. Northern blot analyses indicated that related transcripts are present in aleurones, coleoptiles, endosperms, internodes, leaves, ovules, roots and root tips, with highest levels of expression in the aleurones and endosperms. PMID- 1302633 TI - Efficient initiation of translation at non-AUG triplets in plant cells. AB - The efficiency of translation initiation at triplets differing at one residue from AUG was tested by transient expression in protoplasts from two different plant species. All possible alternative codons were tested. Some triplets showed significant CAT activity, with CUG (30% of the AUG activity) being most active. Most others had between 5 and 15% of the activity obtained from AUG, whereas UUG and AUC yielded about 2% and the two composed only of purines, AAG and AGG, had no significant activity. Translation initiation from AUC, especially, responded to leader sequences outside the immediate context which did not affect translation initiation from AUG. PMID- 1302634 TI - A pathogen-induced gene of barley encodes a protein showing high similarity to a protein kinase regulator. AB - A full length cDNA of a barley leaf messenger, found to increase in amount during infection attempts by the powdery mildew fungus (Erysiphe graminis), is characterized. The messenger encodes a polypeptide of 261 amino acid residues with a calculated mass of 29.2 kDa and a pI of 4.6. Sequence comparisons as well as serological studies demonstrate that the encoded protein is closely related to a family of mammalian proteins believed to have functions associated with the multifunctional Ca(2+)-dependent protein kinases. PMID- 1302635 TI - The promoter of the rice gene GOS2 is active in various different monocot tissues and binds rice nuclear factor ASF-1. AB - A single copy gene has been isolated, termed GOS2, from rice. Sequence comparison revealed highly similar genes in mammals and yeast, indicating that GOS2 encodes an evolutionary conserved protein. GOS2 mRNA was detected in all tissues examined. When the upstream region was translationally fused to the reporter gene gusA it was found to drive expression in a variety of rice tissues and in cell suspensions of other monocot species following introduction by particle bombardment. Therefore, the GOS2 promoter is potentially useful for genetic engineering of monocots. A DNA-binding activity from rice, termed rice ASF-1, with similar binding specificity as the cloned tobacco transcription factor TGA 1a, was found to bind to a TGACG sequence motif in the GOS2 promoter. Possible roles for rice ASF-1 in the transcriptional activation of the GOS2 promoter are discussed. PMID- 1302636 TI - Molecular characterization of cDNA encoding for adenylate kinase of rice (Oryza sativa L.). AB - Two types of genes (Adk-a, and Adk-b) encoding for adenylate kinase (AK, EC 2.7.4.3.) were isolated from the cDNA library constructed from poly(A)+ RNA of rice (Oryza sativa L.). Two cDNAs were heterogeneous at 5' and 3' ends of non coding sequences and had possible polyadenylation signals. One of the genes, Adk a, had 1154 bp sequences encoding 241 amino acid residues, while the other type, Adk-b, contained 1085 bp sequences encoding for 243 amino acid residues. Homology between Adk-a and Adk-b was 73.7% in nucleotide sequences, and 90.8% in amino acid level. Two genes showed about 53% homology to bovine mitochondrial adenylate kinase (AK2) at nucleotide and amino acid levels. Concerning the codon usage of rice AK genes, T was abundant at the third position of a codon in the reading frames. In order to examine the enzyme activity of the protein encoded by the rice cDNA, Adk-a was cloned into an expression vector, pUC119, which was introduced into Escherichia coli strain CV2, a temperature-sensitive mutant of adenylate kinase. We found that the transformant carrying the rice Adk-a gene in the sense orientation recovered cell growth at non-permissive high temperature (42 degrees C) and expressed enzyme activities higher than the untransformed CV2 and the transformant possessing Adk-a cDNA in the antisense orientation. These observations suggest that rice Adk-a codes a biologically active enzyme. Furthermore, sucrose was found to regulate the transcription of AK genes in rice cell cultures. Organ related accumulation of mRNA in whole plants was also found. PMID- 1302637 TI - Expression pattern of a tobacco lipid transfer protein gene within the shoot apex. AB - A genomic clone coding for a putative lipid transfer protein was isolated from Nicotiana tabacum. The gene is expressed in all aerial organs of the tobacco plant, with expression being highest in the upper part of the plant and declining towards the base (i.e. with increasing age). In the shoot apex transcript levels are highest in the LI layer, lower in the underlying cell layers, and are again higher in the submeristem region. This pattern is markedly different from those previously described for genes expressed within the shoot apex. PMID- 1302638 TI - Genome reorganization in Nicotiana asymmetric somatic hybrids analysed by in situ hybridization. AB - In situ hybridization was used to examine genome reorganization in asymmetric somatic hybrids between Nicotiana plumbaginifolia and Nicotiana sylvestris obtained by fusion of gamma-irradiated protoplasts from one of the parents (donor) with non-irradiated protoplasts from the other (recipient). Probing with biotinylated total genomic DNA from either the donor or the recipient species unequivocally identified genetic material from both parents in 31 regenerant plants, each originating from a different nuclear hybrid colony. This method, termed genomic in situ hybridization (GISH), allowed intergenomic translocations containing chromosome segments from both species to be recognized in four regenerants. A probe homologous to the consensus sequence of the Arabidopsis thaliana telomeric repeat (5'-TTTAGGG-3')n, identified telomeres on all chromosomes, including 'mini-chromosomes' originating from the irradiated donor genome. Genomic in situ hybridization to plant chromosomes provides a rapid and reliable means of screening for recombinant genotypes in asymmetric somatic hybrids. Used in combination with other DNA probes, it also contributes to a greater understanding of the events responsible for genomic recovery and restabilization following genetic manipulation in vitro. PMID- 1302639 TI - A functional promoter shift of a chloroplast gene: a transcriptional fusion between a novel psbA gene copy and the trnK (UUU) gene in Pinus contorta. AB - A comparative transcription analysis of the chloroplast trnK-psbA-trnH region of the two pine species Pinus contorta and Pinus sylvestris is reported. The chloroplast genome of P. contorta has previously been shown to contain a duplicated psbA gene copy integrated closely upstream of the split trnK gene. This rearrangement has resulted in the gene order psbAI-trnK-psbAII-trnH, where psbAII is the ancestral psbA gene copy. In P. sylvestris, a species which lacks the psbA duplication, transcription of the trnK gene originates from a position 291 bp upstream of the trnK 5' exon, adjacent to a canonical promoter structure. In P. contorta, the corresponding promoter structure has been separated from the trnK gene by the insertion of psbAI, and has, in addition, been partially deleted. Analysis of the transcriptional organization of the trnK-psbA-trnH region of the two pine species revealed that the trnK gene in P. contorta is transcriptionally fused to the inserted psbAI gene copy. As a result, trnK is under the control of the psbA promoter in this species and has therefore acquired psbA-like expression characteristics. In P. sylvestris, accumulation of trnK transcripts is not significantly higher in light-grown than in dark-grown seedlings. In contrast, the level of trnK transcripts in P. contorta is approximately 12-fold higher in the light than in the dark. When light-grown seedlings of the two pine species were compared, an approximately 20-fold higher level of trnK RNAs was found in P. contorta. In both pine species, evidence was obtained for trnK-psbA and psbA-trnH co-transcription. PMID- 1302640 TI - Temporal and spatial expression of a thiolprotease gene during pea ovary senescence, and its regulation by gibberellin. AB - Clones encoding a thiolprotease (tpp) have been isolated from a cDNA library of unpollinated, senescent pea ovaries and its pattern of expression during both ovary senescence and parthenocarpic development have been studied. The sequence of the tpp cDNA displays a high similarity with other plant and animal thiolproteases of the papain group. The homology is highest around the Cys-His of the active centre; a 109 amino acid sequence at the carboxy terminus was found to be homologous only to thiolproteases of plant origin; this part of the mRNA is also present in another pea mRNA that exhibits similar patterns of induction. tpp mRNA shows a temporal pattern of accumulation that precedes that observed for proteolytic activity. Such accumulation did not occur when ovaries were induced to grow parthenocarpically by gibberellic acid (GA) treatment; furthermore the initial low level of expression present in ovaries decreased after GA treatment, indicating that the gene is down-regulated by gibberellins. Spatially, tpp mRNA is localized mainly within the ovule and ovary vascular elements, and transiently within the endocarp of senescent ovaries. This pattern of expression precedes the development of the cytopathogenic effects observed as unpollinated ovaries undergo senescence. PMID- 1302641 TI - Four distinct nuclear proteins recognize in vitro the proximal promoter of the bean seed storage protein beta-phaseolin gene conferring spatial and temporal control. AB - A proximal promoter (-422/-13) of the bean seed storage protein beta-phaseolin gene contains cis-regulatory elements conferring spatial and temporal gene regulation. To correlate trans-acting elements with these cis-elements, we performed gel mobility shift and exonuclease III protection assays using bean seed nuclear proteins, and identified target sequences of four DNA-binding proteins associated with this promoter. Three CANNTG motifs, CACGTG (-248/-243), CACCTG (-163/-158), and CATATG (-100/-95), were determined as target sequences of the same DNA-binding protein designated CAN. Competition assays using oligonucleotides containing the wild-type or mutated CANNTG motif indicated that the CANNTG motif appears to be a preferred target sequence for CAN binding. Competition assays also demonstrated that DNA-binding protein AG-1 binds to AAAAAG(A/G)CAA (-356/-347, -191/-182), CA-1 binds to two CA-rich sequences (-201/ 192, -175/-160), and that a TATA-box binding protein binds to either TATATAA ( 43/-37) or TATAAA (-32/-27) or both. Based on these and other results, it is proposed that CACGTG motif (-248/-243) is a major cis-acting regulatory element conferring spatial and temporal control of the beta-phaseolin gene. PMID- 1302642 TI - A gibberellin-regulated gene from wheat with sequence homology to cathepsin B of mammalian cells. AB - A previous report described several cDNAs corresponding to mRNAs which accumulated in wheat aleurone layers treated with gibberellic acid (GA) (Baulcombe and Buffard, 1983). The protein sequence deduced from one of these clones (2529) has extensive similarity to the thiol protease, cathepsin B from mammalian cells. Southern analysis of wheat DNA has shown that the 2529 mRNA is encoded by a small family of genes carried on the group 4 chromosome. The nucleotide sequence of a member of the gene family expressed at a low level in aleurone layers and the use of a primer extension assay to identify a clone of a member of the gene family producing an abundant mRNA are reported. The 2529 mRNA accumulates in the scutellum and the aleurone layer of germinating grains where its expression is regulated by GA. In the scutellum the expression was restricted to the parenchyma, suggesting that the 2529 product may have a role other than for mobilization of the endosperm. PMID- 1302643 TI - The root-knot nematode resistance gene (Mi) in tomato: construction of a molecular linkage map and identification of dominant cDNA markers in resistant genotypes. AB - A dominant allele at the Mi locus on chromosome 6 of tomato (Lycopersicon esculentum Mill) confers resistance to three species of root-knot nematodes (Meloidogyne). The resistance, which is associated with a localized necrotic response, was originally introduced into tomato from the wild species Lycopersicon peruvianum. As a step towards the molecular cloning of Mi, we have identified closely linked DNA markers from both cDNA and genomic DNA libraries as restriction fragment length polymorphisms (RFLPs). DNA from tomato populations segregating for nematode resistance was analyzed to generate a high-resolution genetic map of this region. Additional information on gene order was obtained by comparing the size of the introgressed L. peruvianum chromosomal segment within a collection of nematode-resistant tomato lines. Among the four cDNA markers that are tightly linked to Mi, three are dominant, i.e. L. peruvianum-specific. One cDNA marker corresponds to a gene family comprising 20-30 members, one of which is diagnostic for all nematode-resistant genotypes tested. The presence of non homologous sequences around the Mi gene may contribute to the suppression of recombination in this region of the genome in crosses heterozygous for Mi. The potential of 'walking' from closely linked markers to Mi is discussed. PMID- 1302644 TI - Identification of an S-locus glycoprotein allele introgressed from B. napus ssp. rapifera to B. napus ssp. oleifera. AB - Self-incompatible Brassica napus ssp. oleifera lines were generated by introgressing the S-locus from the self-incompatible B. napus ssp. rapifera Z line into the self-compatible cultivars, Topas and Regent, resulting in T2 and R2, respectively. Screening of a cDNA library made from R2 stigma RNA produced several candidate SLG (S-locus glycoprotein) cDNAs. One of the cDNAs, A14, was found to be represented in only the R2, T2 and Z lines. In addition, the corresponding A14 gene was demonstrated to segregate with the T2 self incompatibility phenotype in an F2 population derived from a cross between T2 and Topas, and to exhibit high mRNA levels in the stigmas prior to anthesis. Sequence analysis of the A14 cDNA revealed close homology to B. oleracea SLG alleles associated with a Class I high activity self-incompatibility phenotype. PMID- 1302645 TI - RNA binding characteristics of a 16 kDa glycine-rich protein from maize. AB - We have previously described a developmentally regulated mRNA in maize that accumulates in mature embryos and is involved in a variety of stress responses in the plant. The sequence of the encoded 16 kDa protein (MA16) predicts that it is an RNA-binding protein, since it possesses a ribonucleoprotein consensus sequence type RNA-binding domain (CS-RBD). To assess the predicted RNA binding property of the protein and as a starting point to characterize its function we have used ribohomopolymer-binding assays. Here we show that the MA16-encoded protein binds preferentially to uridine- and guanosine-rich RNAs. In light of these results a likely role for this protein in RNA metabolism during late embryogenesis and in the stress response is discussed. PMID- 1302646 TI - Ears and teeth: how dentists can help vestibular patients. PMID- 1302647 TI - Strength and bite, Part 2: Testing isometric strength using a MORA set to a functional criterion. AB - The effect on isometric strength of biting on three intraoral devices and habitual occlusion was analyzed. Only subjects who showed a relative weakness to the Isometric Deltoid Press (IDP) when biting as opposed to maintaining the mandible in an unsupported rest position were included in the study. Both in the original 35 subjects and the 23 subjects returning on the second day, performance wearing the appliance set by a functional criterion of peak strength (locking) to the IDP was significantly greater than wearing a placebo appliance and a bite raising appliance that deflected the mandible 1 mm to the left. Strength biting on the appliance set by a functional criterion was significantly greater than all these conditions. Strength biting in habitual trials that were matched with the deflection condition was found to be significantly greater than that biting in the placebo condition. It was concluded that a relationship does exist between bite and isometric strength. Previous speculation about the role of placebo effect was not substantiated by the data gathered in this experiment. PMID- 1302648 TI - Influence of mucosal mechanoreceptors on anterior temporalis EMG activity in patients with craniomandibular dysfunction: a preliminary study. AB - An analysis of saliva swallowing and tonic electromyographic (EMG) activity was undertaken in 15 young adult patients with craniomandibular dysfunction with and without a palatal base inserted. Recordings were performed by placing surface electrodes on the right and left anterior temporal muscles. Saliva swallowing and tonic activity were initially recorded with and without the palatal base inserted. After one week of continuous use of the palatal base, EMG activity was recorded again. Nonsignificant differences in EMG activity were observed in the studied conditions. EMG results do not support the therapeutical use of palatal base as a conservative and reversible treatment in patients with craniomandibular dysfunction. PMID- 1302649 TI - Evaluation of pressure pain threshold in head and neck muscles by electronic algometer: intrarater and interrater reliability. AB - Using a new electronic algometer, the mean values and standard deviations of pressure pain threshold and the intrarater and interrater reliability were evaluated on 13 muscles of the human head and neck region. The subjects were 40 healthy individuals, 21 females and 19 males. A comparison with data obtained from contralateral muscles failed to demonstrate significant differences. Statistically significant correlation coefficients were obtained from the values of intra-examiners and inter-examiners in all muscles except the medial pterygoid and middle sternocleidomastoid muscle in male subjects (p < 0.05). This study showed that the electronic algometer could be recommended for evaluation of the pressure pain threshold of human head and neck muscles in clinical and experimental studies. PMID- 1302650 TI - Temporomandibular joint vibration analysis in a sample of non-patients. AB - In a sample of 20 non-patients, 60% of the subjects had an absence of subjective temporomandibular joint (TMJ) complaints (noises/sounds) that agreed with objective joint vibration analyses (electrovibratography). Among the remaining 40% of subjects, only 50% of the examined joints showed agreement between subjective and objective findings. Subjects appeared to be unable to reliably detect "weak" (early) symptoms of TMJ dysfunction but were able to reliably detect "strong" (late) symptoms of TMJ dysfunction and possibly disease. As measured through active protrusion and laterotrusion of the mandible, the guidance angles of the anterior teeth could not explain the absence and presence of TMJ vibrations. PMID- 1302651 TI - Video display terminal operation: a potential risk in the etiology and maintenance of temporomandibular disorders. AB - Surveys indicate over 50 million Americans, mostly women, currently operate video display terminals (VDTs) at home or in the workplace. Recent epidemiological studies reveal more than 75% of approximately 30 million American temporomandibular disorder (TMD) sufferers are women. What does the VDT and TMD have in common besides an affinity for the female gender? TMD is associated with numerous risk factors that commonly initiate sympathetic nervous system and stress hormone response mechanisms resulting in muscle spasms, trigger point formation, and pain in the head and neck. Likewise VDT operation may be linked to three additional sympathetic nervous system irritants including: (1) electrostatic ambient air negative ion depletion, (2) electromagnetic radiation, and (3) eyestrain and postural stress associated with poor work habits and improper work station design. Additional research considering the roles these three factors may play in the etiology of TMD and other myofascial pain problems is indicated. Furthermore, dentists are advised to educate patients as to these possible risks, encourage preventive behaviors on the part of employers and employees, and recommend workplace health, safety, and ergonomic upgrades when indicated. PMID- 1302652 TI - Temporomandibular joint adaptation following inferior repositioning of the maxilla in adult monkeys. AB - Treatment of adults with vertical maxillary deficiency (short faces) has continually been an intriguing challenge for surgeons and orthodontists. For this category of patients, the introduction of simultaneous bone grafting and Le Fort I osteotomy has opened the door for improved treatment. However, despite the improved surgical techniques, surgeons have been reluctant to increase the vertical dimension of the maxilla by Le Fort I osteotomy with interpositional bone grafts because of inconsistent and variable stability after surgery. This study examines structural and functional adaptation of the adult temporomandibular joint and stability in a primate model following surgical lengthening of the maxilla in the vertical dimension. Results suggest that maxillary surgery and autorotation can alter condylar stress within physiologic ranges. However, further studies are indicated to clarify the surgery's long-term effect. PMID- 1302653 TI - Rheumatoid arthritis and its implications in temporomandibular disorders. AB - Rheumatoid arthritis is known to afflict the temporomandibular joint (TMJ) with common symptoms including pain during function, tenderness on palpation, stiffness, and crepitus. New evidence suggests that metalloproteinases may be responsible for tissue changes that occur in rheumatoid arthritis. These enzymes are collagenase, gelatinase, and proteoglycanase. Antiinflammatory drugs are the first line of management for pain and inflammation in rheumatoid arthritis. This paper, however, suggests that because increased joint load is believed to cause a greater expression of destructive metalloproteinase, it is appropriate to assess even the asymptomatic temporomandibular joint and the muscles of mastication for early objective signs of dysfunction or discomfort. Interceptive management, by the use of load-reducing appliance therapy, may enable reduction of the expression of destructive metalloproteinase within the joint, thereby reducing joint destruction. PMID- 1302654 TI - Comparison of MMPI scores with self-report of sleep disturbance and bruxism in the facial pain population. AB - Sleep disturbance and bruxism are common clinical characteristics of the chronic facial pain patient. Previous studies have shown that chronic pain patients reporting disturbed sleep show more psychopathology and respond less readily to treatment. Bruxism has been linked to emotional stress and periods of difficult life change. The present study explored the question of whether sleep disturbance or bruxism are useful predictors of psychopathology in the facial pain population. Psychopathology was measured by using the Minnesota Multiphasic Personality Inventory (MMPI). It was predicted that facial pain patients who reported sleep disturbance or bruxism would correlate with more elevated scores on the MMPI profiles. The results of the study revealed a strong association between self-report of disturbed sleep and higher MMPI scores. No difference between the MMPI scores of bruxers and non-bruxers was found. It was concluded that sleep disturbance may be an effective predictor of psychological disturbance within the facial pain population, while bruxism was not found to be associated with psychological disturbance as measured by the MMPI. PMID- 1302655 TI - A too-polite silence about shoddy science: dynamic strength testing and beyond. PMID- 1302656 TI - Changes in elongation of falx cerebri during craniosacral therapy techniques applied on the skull of an embalmed cadaver. AB - Craniosacral therapy supports that light forces applied to the skull may be transmitted to the dura membrane having a therapeutic effect to the cranial system. This study examines the changes in elongation of falx cerebri during the application of some of the craniosacral therapy techniques to the skull of an embalmed cadaver. The study demonstrates that the relative elongation of the falx cerebri changes as follows: for the frontal lift, 1.44 mm; for the parietal lift, 1.08 mm; for the sphenobasilar compression, -0.33 mm; for the sphenobasilar decompression, 0.28 mm; and for the ear pull, inconclusive results. The present study offers validation for the scientific basis of craniosacral therapy and the contention for cranial suture mobility. PMID- 1302657 TI - [Quality control of standard nursing care assisted by computer systems]. PMID- 1302658 TI - [Patient postmortem review of quality of nursing records]. PMID- 1302659 TI - [Clinical analysis of cardiac sudden death of elderly patients]. PMID- 1302660 TI - [Nutritional care of pre- and post-operative patients with extended radical surgery of carcinoma of the rectum]. PMID- 1302661 TI - [Investigation of air pollution in extensive burn units]. PMID- 1302662 TI - [Hand cleaning method in the stomatologic clinic]. PMID- 1302663 TI - [Cardiac transplantation and its monitoring]. PMID- 1302664 TI - [Pre- and post-operative care of orthotopic cardiac transplantation]. PMID- 1302665 TI - Reading the medical record. I. Analysis of physicians' ways of reading the medical record. AB - Physicians were interviewed about their routines in everyday use of the medical record. From the interviews, we conclude that the medical record is a well functioning working instrument for the experienced physician. Using the medical record as a basis for decision making involves interpretation of format, layout and other textural features of the type-written data. Interpretation of these features provides effective guidance in the process of searching, reading and assessing the relevance of different items of information in the record. It seems that this is a skill which is an integrated part of diagnostic expertise. This skill plays an important role in decision making based on the large amount of information about a patient, which is exhibited to the reader in the medical record. This finding has implications for the design of user interfaces for reading computerized medical records. PMID- 1302666 TI - A scanning system for digital analysis of cineangiography films. AB - A system for scanning and digital analysis of cinefilms is presented and its performance is compared with entirely digital radiographic equipment. Apart from the difference between logarithmic and linear gray-scale representation, a higher noise level was found in the scanning system. When its spatial resolution was assessed visually, it was comparable to that of the digital system, although lower than when the cinefilming and scanning steps were evaluated separately. Algorithms for the correction of varying exposure and geometric ("pin-cushion") distortion are also presented. It is concluded that digital analysis after scanning of cinefilms can be a useful alternative to completely digital cineradiographic studies. PMID- 1302667 TI - A computerized analysis system for vigilance studies. AB - A digital signal analysis system for vigilance studies is presented. The analysis is based on adaptive segmentation, band pass filtering, nonlinear eye movement detection and rule-based decision making. A preliminary evaluation of seven subjects falling asleep showed that the system is able to detect small vigilance fluctuations reliably. PMID- 1302668 TI - Reading the medical record. II. Design of a human-computer interface for basic reading of computerized medical records. AB - A user interface for reading the medical record was designed and implemented on a workstation with a 19-inch colour screen. The text is presented on imitations of paper-pages. The pages are organized in bundles which are dynamically connected to scrollable index lists. The turning of pages on the screen is the fundamental concept of the interface. A page can be turned by a mouse-click or by a circular mouse-movement. Elaborated feedback is given to the user in order to provide effortless orientation and navigation. The interface supports the basic ways of use identified in our analyses of reading habits. It also enables human perceptual and cognitive skills to be used. It seems very easy to learn and efficient in use. PMID- 1302669 TI - PRIST-2: a Graphic User Interface based tool for the development of medical software. AB - A 4th generation tool, called PRIST-2, is presented that has been designed as an interactive environment for the rapid prototyping of clinical applications in a large-scale Hospital Information System project. We adopted an SQL-based commercial Relational Data Base Management Systems (RDBMS) to guarantee portability on different hardware and operating systems. Relational databases, however, are characterized by a simple data structure and do not incorporate the application semantics required to ensure a high degree of data independence. To reach this goal, we propose an extension to the relational model, adding some of the main characteristics of the Object Oriented Data Base Management Systems (OODBMS) approach, such as "types" and "encapsulation". PMID- 1302670 TI - Using the job-exposure matrix for elaborating job histories. AB - A first software (JHS) for the elaboration of job histories oriented toward risks was designed and results published In an article "A software for the elaboration of Job Histories". This article presents a second software (JES), based on the use of a job-exposure matrix designed for one company. The matrix is essentially a database, an organized gathering of information concerning the company. The two softwares are inter-faced and both run on a PC. When properly exploited, the two softwares can serve as an asset for epidemiological studies dealing with occupational health. PMID- 1302671 TI - A low-cost system for digital image processing of moving images in real time: application to X-ray fluoroscopy. AB - A low-cost image processing system and two real-time digital image processing algorithms using parallel processing have been developed to provide automatic equalization of moving images at video frequencies. The algorithms differ in the processing time required and the characteristics of the final image. The system takes an entire image from the video sequence, digitizes it, automatically calculates its histogram and the lowest and highest useful grey levels, equalizes the histogram, and finally converts it to the analogue image. Methods were applied to X-ray fluoroscopy (angiography) images, which are usually saturated or of uniform intensity (low contrast), leading to information loss. An application of these methods is in interventional radiography, which requires images in real time. PMID- 1302672 TI - Computer-assisted rheological evaluation of microsamples of mucus. AB - Dynamic viscoelasticity measurements are required in many studies on biological fluids and they can be performed by determining the corresponding strain when a sinusoidal shear stress is applied to a sample. In several circumstances the amount of fluid that can be obtained for analysis in physiological conditions does not exceed microliters. In this context, the microrheometer technique is a useful approach to determine the dynamic rheological profile of the samples. However, the manual calculation of the desired parameters is tedious and time consuming. This paper describes a menu-oriented program in order to facilitate its use by non-experts. The comparison between manual and computer-aided calculations demonstrated that the program reduced the time of measurement, and reduced intra- and interobserver variations. The program was developed on an IBM compatible PC in Microsoft C 5.1, and tested in a blind study to check the advantages in terms of time and reproducibility of the system verified by the concordance of two independent observers (interobserver influence) in two different occasions (intraobserver influence). PMID- 1302673 TI - The determination of the absolute bioavailability for drug substances with long elimination half-lives (with PC-programs for the method of truncated areas). AB - A survey is given of the methods for the determination of the absolute bioavailability for drug substances with long elimination half-lives. All methods depend on the assumption of linear pharmacokinetics. Emphasis is laid on Urso and Aarons' regression method of truncated areas-under-the-curve (AUC) to obtain estimates of the absolute bioavailability, F, and the absorption rate constant, ka, without obeying the otherwise general rule of following blood or plasma levels for at least three times the terminal half-life. It is shown by simulation when the linear and when the logarithmic trapezoidal rule is to be used for the calculation of the AUC. Two PC-programs for the regression method of truncated areas are presented: one program (SIMF&KA.EXE) simulates, based on tentative pharmacokinetic parameters, whether a blood sampling scheme, together with the precision of the analytical assay, is adequate to obtain accurate and precise estimates of F and ka; the method is insensitive to large variations in the tentative value of the elimination half-life. The other program (ESTF&KA.EXE) provides estimates of F and ka, with standard deviations of the estimates, from empirical data. PMID- 1302674 TI - Computer processing of artifact and arrhythmias in heart rate variability analysis. AB - Analysis of heart rate variability (HRV) with Holter monitoring is often difficult due to excessive artifacts and arrhythmias. While short sudden surges are treated successfully by most methods, slow heart rate (HR) variations, nocturnal trapezoidally-shaped HR increases and special types of arrhythmias which are similar to normal HRV fluctuations may distort further time domain and spectral analysis. This paper examines the advantages and disadvantages of different methods for preprocessing of HR data. We have developed the following approach to the analysis of HRV. (1) A combination method based on the absolute difference between HR values and both the last normal HR value and an updated mean is used for removal of artifacts and arrhythmias. This method can detect both sudden surges in HR values as well as longer periods of noise combined with slow normal variations. An additional stage of wild point removal is then optionally applied. (2) Certain special problems such as large T-waves, bigeminal rhythm, slow HR variations and nocturnal trapezoidally-shaped HR increases are also identified. Although none of the algorithms can be applied successfully to all cases, the final computer analysis for preprocessing described in the present study has proved to be superior to the simplified methods which are usually used and provides more suitable data for HRV analysis. PMID- 1302675 TI - Special computer graphical method for detection of myocardial infarction. AB - The application of computer graphics for detection of myocardial infarction is reviewed and a special method is described. It is based on construction of two isointegral maps (Q wave map and ST segment map) realized in contour representation and using the Selvester distribution of the left ventricle. PMID- 1302676 TI - GCG Stacks: a friendly interface for the GCG programs. AB - A 'PLUS' stack which provides a friendly user interface for the GCG suite of programs is presented. The interface takes advantage of the whole set of programming tools available in a graphical and object-oriented environment and its major features include: (i) an efficient management of the on-line help documents, and (ii) a flexible editor for macrocommands. The former facilitates finding specific information in the huge documentation bundled with the GCG suite, and the latter is useful whenever several GCG programs must be run in sequence with automatic piping of the intermediate results. PMID- 1302677 TI - Periodontal healing of replanted dog teeth stored in Viaspan, milk and Hank's balanced salt solution. AB - This study examined, histologically, periodontal healing and root resorption of replanted dogs teeth stored in Viaspan for different time periods and compared these healing patterns to those after storage in milk or Hank's balanced salt solution (HBSS). Seventy-two beagle incisors were endodontically treated, extracted, randomly divided and placed in Viaspan or milk for 6, 12, 24 and 36 h, and Viaspan or HBSS for 36, 48, 72 and 96 h, after which they were replanted. Four negative control teeth were immediately replanted while four positive controls were allowed to dry for one hour before replantation. All replanted teeth were splinted for 14 days. Two months after replantation the dogs were killed and the teeth histologically examined for healing of the supporting tissues. For Viaspan neither replacement nor inflammatory root resorption was seen after 6 and 12 h storage. A statistically significant rise in the incidence of replacement resorption was seen at 24, 36 and 48 h which decreased again at 72 and 96 h to levels equal to storage for 6 and 12 h. The occurrence of inflammatory root resorption was low and significantly increased only at 48 h after which it decreased significantly again. Viaspan proved superior to milk as a storage medium. Teeth stored in HBSS showed healing results similar to those stored in Viaspan. PMID- 1302678 TI - Observations of acoustic streaming fields around an oscillating ultrasonic file. AB - The steady acoustic streaming generated around straight and precurved oscillating ultrasonic files driven by the Piezon-Master 400 unit was examined in the free field and in small channels using a stereomicroscope. In addition, the effect of file-wall contact on streaming production was also investigated. The results indicated that the ultrasonic files can generate acoustic streaming both in the free field and in the small channel. Higher velocity streaming was observed when smaller size files were employed and when the file was precurved. Light file-wall contact did not totally inhibit streaming while severe file-wall contact inhibited movement of the file and, as a result, no streaming was observed. The positions and length scales of the streaming vortices appeared to be influenced by the presence of boundaries. In the free field, two rows of vortices were situated along the sides of the file while in the small channel, the vortices were positioned above the surface of the file. These results indicated that it is possible for acoustic streaming to occur in a confined space as in a root canal provided that severe file-wall contact is avoided. It is therefore recommended that light filing or allowing the file to freely vibrate during some stage of treatment should be carried out in order to generate streaming in the root canal. PMID- 1302679 TI - Morphology of the mineralizing front and observations of reparative dentine following induction and inhibition of dentinogenesis in the rat incisor. AB - An extra oral approach was made to 26 pairs of Wistar rat incisors and a small bur used to expose the pulps which were then dressed with either calcium hydroxide paste (Pulpdent) zinc oxide-eugenol cement (Kalzinol) or a triamocinolone acetonide/tetracycline containing cement (Ledermix). Animals were sacrificed at 7 days, incisors removed, a window cut to the pulp opposite the site of exposure, soft tissues removed with 7% NaOCl for 30 minutes before teeth were dehydrated in graded concentrations of acetone and gold coated for examination under SEM. Calcium hydroxide produced rapid complete repair with a remarkably regular formation of calcospherites, except for a zone of relative inhibition perforated by nutrient canals at the periphery of each lesion. Both zinc oxide-eugenol and triamcinolone acetonide cements inhibited both bridging of the defect created by the exposure and dentine formation in the surrounding pulpal wall. Data was grouped according to the degree of hard tissue repair. The results were statistically significant (Chi-square p < or = 0.001). This method demonstrated qualitative and quantitative differences in the repair process resulting from chemical variations in the dressings applied. PMID- 1302680 TI - Effect of cervical coating of ethyl cellulose polymer and metacrylic acid copolymer on the radicular penetration of hydrogen peroxide during bleaching. AB - Extraradicular leakage of oxidizing agents during bleaching is an undesirable event and thus need to be prevented. The effect of external cervical coating of ethyl cellulose (EC) and metacrylic acid copolymer (MAC) on the radicular penetration of hydrogen peroxide during intracoronal bleaching was examined. Single rooted human premolars extracted for orthodontic reasons were used. The cementum covering the cemento-enamel junction was mechanically removed and the teeth treated endodontically and bleached with 30% hydrogen peroxide. Radicular hydrogen peroxide penetration was measured before coating the teeth and after applications of 1-3 layers of EC or 3 layers of MAC external cervical coatings. It was found that the radicular penetration of 30% hydrogen peroxide was related to the number of layers of cervical EC coatings. Application of one layer of EC did not reduce the hydrogen peroxide penetration. Two and three layers of EC reduced the hydrogen peroxide penetration by 38% and 85% respectively. Three layers of MAC reduced the radicular hydrogen peroxide penetration in 83%. Statistically, a highly significant difference was found between the teeth coated with three layers of either EC or MAC and the noncoated teeth (p < 0.001). It was concluded that application of ethyl cellulose or metacrylic acid copolymer to exposed cervical root surfaces may effectively prevent extraradicular leakage of bleaching agents. PMID- 1302681 TI - A comparison of four root canal obturation methods employing gutta-percha: a computerized analysis of the internal structure. AB - The purpose of the present investigation was to compare the internal structure of gutta-percha for presence/absence of empty spaces when used in four different obturation methods: thermoplastic, chloroform-softened, thermomechanical, and warm lateral condensations. Each obturation was performed five times in a metal mold representing a root canal system. Following obturation the mold was disassembled and the gutta-percha was freeze-fractured at the 1.0, 3.5, and 6.5 mm levels as measured from the tip of the obturations. The fractured gutta-percha was placed in a scanning electron microscope, the image transferred to a computer, and converted to digital data. The results were subjected to statistical evaluation. The results demonstrated no difference between the obturation methods at the 1 mm level, however at the 3.5 mm level, thermomechanical condensation produced an internal structure characterized by a greater number of empty spaces (p < 0.0007). At the 6.5 mm level, thermomechanical condensation differed only from the chloroform-softened gutta percha (p < 0.01). PMID- 1302682 TI - Traumatic injuries to primary teeth in Mexico City children. AB - The purpose of this retrospective study was to analyse traumatic injuries to primary teeth in children attending an emergency dental service in a pediatric hospital in Mexico City. A total of 563 children 6-mo to 7 yrs-old were treated during the period from January 1981 to December 1987. The 563 children presented 936 traumatic dental injuries. The most common type of trauma was soft tissue injury, followed by luxation and avulsion. More males presented with traumatic injuries (61.8%) than females (38.2%). In both sexes, maxillary teeth received more traumatic injuries than mandibular teeth. Children 2-3 yrs old presented the highest number of injuries (195) followed by the 4-5 and 6-7 year-olds. The largest number of injuries were seen during winter (36%) followed by summer (25%), spring (21%) and fall (18%). PMID- 1302683 TI - Two-dimensional distribution of sound velocity in ground sections of dentin. AB - The longitudinal velocity of sound in a specific material depends, amongst others, on the material's density and elasticity (Young's Modulus). Ultrasound therefore may be used for indirect characterization of materials. In this paper a method is described which allows high resolution measurements on coplanar ground sections of human teeth. The results are presented in two-dimensional velocity profiles. There is evidence from the first images, that longitudinal sound velocity (LSV) in dentin varies depending on the location. The use of LSV may be another way to characterize hard dental tissues physically, and to monitor induced changes. PMID- 1302684 TI - A case of progressive external root resorption treated with surgical exposure and composite restoration. AB - Progressive external, root resorption was observed apical to the alveolar crest on the buccal surface of a tooth. The area of root resorption was surgically exposed. To gain access to the root resorption cavity osteoectomy was performed. The soft tissue in the resorption cavity was removed and a composite filling (Retroplast) was placed in the cavity using a dentine bonding system (Gluma). The pulp was removed and the root canal was obturated with gutta-percha points and root canal sealer (AH26). Eight months after treatment no further root resorption was observed. Increased pocket depth and slight bleeding on probing in the area of resorption were evident. PMID- 1302685 TI - Influence of irrigation and intracanal dressing on the healing process of dogs' teeth with apical periodontitis. AB - Dogs' teeth with apical periodontitis were treated endodontically, Dakin's solution being used in an experimental group as the irrigation solution, and camphorated paramonochlorophenol as an intracanal dressing. For a second group of teeth, the irrigation solution used was physiologic saline, dry cotton only being placed into the pulpal chamber to take the place of an intracanal dressing. In a second visit, overinstrumentation and a new application of the same kind of dressing were performed, the root canals being then filled with gutta-percha cones and zinc oxide-eugenol cement. Other specimens were treated, in one visit, where physiologic saline or Dakin's solution were the irrigation solutions. The animals were sacrificed 6 months after the obturation of the root canals. Histologic exams showed better results for the experimental group where Dakin's solution and camphorated paramonochlorophenol had been used, with signs of repair characterized by newly formed cementum and bone tissue, as well as a marked reduction in size of the periapical lesions. No differences were seen in the results with physiologic saline or Dakin's solution as irrigants. PMID- 1302686 TI - Reasons for and incidence of tooth mortality in a Swedish population. AB - Longitudinal studies on tooth mortality are rare but the reasons for tooth mortality have been studied by several authors. The aims of this investigation were to study the reasons for and incidence of tooth mortality in an earlier described Swedish population of 200 patients on two occasions with an interval of 5-7 years, and to see if the reasons for extractions were correlated to posts, crowns or endodontic status, respectively. 197 (4.0%) of the 4889 teeth registered at the first examination were lost during the interval. 65 (33%) of the lost teeth were endodontically treated. 44 (68%) of these were registered as having one or more root with a root-filling ending more than 2 mm from the apex and 29 (45%) were judged to have an improper seal. In 93 of the 197 lost teeth it was possible to find the reason for extraction from the patient chart. Based on distribution of selected variables, these 93 teeth seemed to be representative of the whole group of 197. It was concluded that tooth losses were evenly distributed in the different age-groups and that above all molars but also premolars were lost more often than teeth in the frontal region. Furthermore, endodontically treated teeth were lost more often than other teeth and the quality of the root-filling affected the risk for losses while crowned teeth did not run a higher risk of being lost than teeth without crowns. Finally, it was found that caries, including pulpitis and apical periodontitis, was the main reason for tooth extractions. PMID- 1302687 TI - An experimental study of the stability of irradiated teeth in the region of the dentinoenamel junction. AB - In this in vitro study we investigated the influence of ionizing gamma rays on the stability in the region of the dentinoenamel junction. We removed the enamel on the labial surface of 30 incisors of bovines up to the dentinoenamel junction, so that a circular area of enamel with a diameter of 2.0 +/- 0.1 mm was left and an enamel cylinder was created. 15 teeth were irradiated by a cobalt-60-source (energy dose 70 Gy). The other 15 teeth were used as controls. Using a material testing apparatus the shear bond strengths were measured by breaking off the enamel cylinders. Furthermore, the breaking modes were investigated in SEM. Comparing the results of the shear bond strength experiments, it was obvious that the stability in the region of the dentinoenamel junction was significantly less among the irradiated teeth than among the non-irradiated teeth. The median value of the gamma ray treated teeth was x = 19.1 MPa and that of the non-ray-treated teeth was x = 37.4 MPa. The non-irradiated teeth showed fractured surfaces only in dentin in 10 cases and in 5 cases in both dentin and enamel. In contrast to that, the irradiated teeth had fractured surfaces in 12 cases exclusively in dentin and only in 3 cases the enamel was also fractured. These results lead us to conclude that changes of biophysical property of teeth can be caused by the influence of ionizing rays. PMID- 1302688 TI - Pulpal and radicular changes following maxillary subapical corticotomy. AB - Pulpal and radicular changes after subapical corticotomy in combination with posterior transfer of the maxilla were studied histopathologically using monkey jaws. When the surgical procedures were successful, the pulp tissues were kept alive, even though some slight atrophy and degeneration appeared. In some cases, however, severe reticular atrophy occurred which might be due to anaemia during operations. PMID- 1302689 TI - Profiling of Propionibacterium acnes recovered from root canal and blood during and after endodontic treatment. AB - This report describes the first results of an ongoing study of bacteremia after endodontic treatment of teeth with Asymptomatic apical periodontitis. After access cavity preparation, microbiological samples were taken from the root canal under aseptic conditions in 4 single-rooted teeth in 4 patients. In treatment of 2 of the patients, the first 3 reamers (sizes 15-25) were deliberately used to a level 2 mm beyond the apical foramen. In 2 patients the instrumentation ended inside the root canal 1 mm short of the apical foramen. Blood samples were taken from the patients during the endodontic instrumentation and 10 min after the treatment was completed. Using lysis-filtration under anaerobic conditions, the blood was passed through a cellulose membrane filter. The filters as well as the root canal samples were incubated using an anaerobic technique. Anaerobic bacteria were isolated from all root canals. In the 2 patients where overinstrumentation had occurred, Propionibacterium acnes was recovered both from the root canals and from the blood samples taken during and after the treatment had been completed. Biochemical profiles, antibiotic susceptibility tests and electrophoresis of soluble proteins revealed that Propionibacterium acnes isolated from the root canal and blood samples were identical within patients, but varied between patients. Facultative anaerobic bacteria including Streptococcus sanguis were recovered from only one root canal sample and not from the blood samples. PMID- 1302690 TI - Ectopic eruption of a maxillary canine following trauma. AB - Traumatic events at an early age may lead to developmental dental anomalies and ectopic tooth eruption. A case is reported in which a traumatic injury at two months of age resulted in the development of supernumerary teeth in the upper right premaxillary region. The maxillary canine ectopically erupted or transposed into the space left by the missing central incisor and eliminated the need for a prosthesis in this region. PMID- 1302691 TI - Generalized "complete" calcific degeneration or pulp obliteration. AB - Extensive calcification of the pulp is a pathologic condition that occurs as an answer to various factors (trauma, caries, periodontal disease). The increase in the amount of calcification may lead to partial or complete radiographic, but not microscopic, obliteration of the pulp chamber and root canals. Complete calcific degeneration (pulpal obliteration) may be found in two forms, generalized or localized. The generalized form which is presented in the present case report is probably part of the aging process. PMID- 1302692 TI - [The problem of respiratory muscle fatigue]. PMID- 1302693 TI - [The cytophysiological characteristics of the gastrointestinal tract epithelium in chum salmon fry during salt water adaptation]. PMID- 1302694 TI - [The efficiency of thermoregulatory reactions in the cooling of the body]. AB - Immersion of the rabbit body model in water of 4 degrees C temperature induced fast cooling of the model even though the heater of the model was 3-fold more powerful than the respective heat-production mechanism in a live rabbit. Only 10 11-fold more powerful heat production was able to keep the model temperature about 37 degrees C. PMID- 1302695 TI - [The acetylcholinesterase activity of the neostriatum in rats running in a T maze]. PMID- 1302696 TI - [The role of the serotoninergic innervation of the hippocampus in sleep organization]. PMID- 1302697 TI - [The neuronal activity of the ventromedial hypothalamus during pharmacological exposures that modulate motivational and emotional states]. AB - Neuronal activity of the ventromedial hypothalamus was studied in food- and water deprived, saturated unrestrained rats and after i. p. administrations of alcohol, nembutal, 5-HT and disulphiram. The neurons whose activity did not depend on motivational states decreased their firing rate. The data obtained suggests that motivational and emotional effects of the ventromedial hypothalamus are based on various cell mechanisms. PMID- 1302698 TI - [Visual recognition processes in monkeys and their neuronal correlates in the visual cortex: the effect of an M-cholinoreceptor blocker]. AB - Unit activity was studied in the visual cortex prior to and after amyzyl administration in monkeys trained for delayed visual differentiation of different colour stimuli. The data obtained suggests that the cholinergic mechanisms of the visual cortex are involved in the visual recognition and seem to play different functional roles at different stages of the behaviour. PMID- 1302699 TI - [The informational significance of the pulse waves of an intracerebral rheoencephalogram]. AB - The evidence obtained on the pulse waves of intracerebral rheoencephalogram in rabbits and cats, suggests active responses of cortical vessels to the loads altering the correlation of the CSF and blood pulse volumes in the process of formation of these waves. The intracerebral rheoencephalogram seems to be able to reflect the changes of both the vascular tone and the brain tissue hydration. PMID- 1302700 TI - [The effect of the ambient temperature and motor activity on brain temperature in bullfinches]. AB - In increasing of the ambient temperature, the difference between the brain and body temperatures diminished from 1.4 degrees C (at the ambient temperature 0 degree C) to 0.5 degrees C (at the ambient temperature +37 degrees C) in bullfinches, the brain temperature being always the lower one. In combination of high ambient temperature and locomotor activity the brain-body temperature difference increased as the body temperature had raised higher than the brain one. PMID- 1302701 TI - [Differential neural influences on the heart rate and contractile force in different reflex reactions]. AB - Chronotropic and inotropic responses of the cat heart to cooling of the nn. vagi, raising of arterial pressure, stimulation of central ends of the nn. vagi, were different under different actions but stable in their character. This makes unreliable the estimation of reflex and tonic effects on the heart on the basis of heart rate alone. PMID- 1302702 TI - [The effect of large doses of corticosteroids on stomach ulcer formation: a new hypothesis]. AB - A new hypothesis is suggested according to which the ulcerogenic effect of large corticosteroid doses is regarded as a consequence of suppression of hypothalamo pituitary-adrenocortical system (HPAS) function. On the 7-th day after the administration of a large hydrocortisone dose to rats the HPAS block was observed. The HPAS block increased the area of hemorrhagic damages of the stomach mucosa induced by a stress factor. Similar data on the ulcer formation were obtained when using intrahypothalamic administration of dexamethasone. The replacement therapy decreased the effect of HPAS block in both cases. The data show that the stomach ulcer formation after the administration of high corticosteroid doses occurs as a result of endogenous hormone production insufficiency. PMID- 1302703 TI - [The role of bile proteins in regulating the secretory function of the liver]. AB - The bile's proteins were found to be one of the factors regulating the intensity of bile production. Hypocholeresis induced by cycloheximide was followed by suppression of the biosynthesis and secretion of the bile's proteins. PMID- 1302704 TI - [The localization and functional status of serotonin-producing structures in the gastrointestinal tract of chum salmon fry]. AB - The data obtained shows that serotoninergic structures of the juvenile Siberian salmon gastrointestinal tract involve individual goblet cells of the mucose epithelium, serotoninergic cells as the components of the stomach cardiac glands, fibre-like structures in subepithelial and muscular layers related, probably, to a neural plexus. The serotoninergic structures decrease in their number towards the distal portion of the tract. PMID- 1302705 TI - [Second messengers in the triggering and adaptational-trophic effects of the antidiuretic hormone]. AB - Vasopressin exerts a triggering effect upon the cells of the osmoregulating epithelium as well modulates this effect. The triggering effect is associated with the stimulation of V2-receptors in the frog bladder, whereas the modulating effect is related to the activation of the V1-receptors. PMID- 1302706 TI - [Stress and arterial hypertension]. AB - Subjects with normal arterial pressure, those with bordering values of the AP and patients with arterial hypertension were studied. The AB, heart rate and diuresis changed independently under stress in the first group subjects, whereas these parameters depended on each other to some extent in the "future patients". PMID- 1302707 TI - [The current problems of the respiratory function of the blood and of gas exchange in the lungs]. PMID- 1302708 TI - [The functional characteristics of the pancreatic mitochondria]. PMID- 1302709 TI - [An analysis of the effect of low-frequency acoustic oscillations on proprioceptor impulse activity]. PMID- 1302710 TI - [The effect of the duodenal mechano- and chemoreceptors on gastric secretory and excretory functions]. PMID- 1302711 TI - [Leon Abgarovich Orbeli in the '50s (pages from reminiscences)]. PMID- 1302712 TI - [Cholin- and serotoninergic mediator systems in cerebrovisceral interaction]. PMID- 1302713 TI - [The spectral characteristics of the effect of central M-cholinolytics on rat behavior under open-field conditions]. AB - Having estimated the rat behaviour in the open-field test, M-cholinolytics were divided into different groups. Haloperidol normalised the disturbance in the behaviour induced by one group M-cholinolytics and had no effect with the other group. The former group seems to have an explicit dopaminergic activity. The groups seem to correspond to different mechanisms of the behavioural activity. PMID- 1302714 TI - [The effect of transcranial electrostimulation in an analgesic regimen on somatosympathetic reflexes]. AB - The mechanisms of inhibitory effect of transcranial electrostimulation in analgesic regime on blood pressor nociceptive reflexes were studied in experiments in rabbits and cats. Considerable inhibition of the late (bulbar) somato-sympathetic reflexes and spino-bulbo-spinal somato-somatic reflexes as well was demonstrated. The probable basis of sympatho-inhibition during transcranial electrical stimulation is a reduction of excitatory input to bulbar sympathoexcitatory neurons. It was revealed in experiments with inhibition of sympatho-excitation elicited by temporal brain ischaemia and local electrical stimulation of different bulbar ventrolateral vasomotor zones. The role of periaqueductal gray activated by transcranial electrical stimulation as a source of inhibition and its opioid mechanisms are discussed. PMID- 1302715 TI - [Changes in the functional activity of the brain stem system that inhibits movement during the development of cataleptiform states]. AB - Electrical stimulation of the n.cuneiformis and medial parabrachial nucleus inducing the inhibition of locomotor behaviour, was performed in cataleptic and non-cataleptic rats. The stimulation of the inhibitory brainstem zones proved to be more effective in cataleptic animals, the state having been induced by a nociceptive stimulus. PMID- 1302716 TI - [The influence of the anterior hypothalamus on the electrical activity of the retina]. AB - Single stimuli applied to the suprachiasmatic and supraoptic nuclei of the hypothalamus evoked short-latency hypothalamo-retinal responses which exert influences upon formation of the "a" and "b" waves of the electroretinogram, the changes of the waves being opposite by character. The effects from the suprachiasmatic and supraoptic levels were opposite, too. PMID- 1302717 TI - [The activation and inhibitory postactivation effects of chemical interoceptive stimulation under normal conditions and in experimental neurosis]. AB - The realisation of hemointeroceptive effects was found to begin with a period of the brain activation. In normal conditions a positive correlation was found between the EEG arousal response and the concentration of mustard administered into the stomach. In experimental neurosis, both regulatory influences of the hemointeroceptive stimulation were decreased. PMID- 1302718 TI - [The characteristics of the correlation of the functional activity, blood supply and structural organization in the sensory-deprived cerebral cortex in rats]. AB - The feature of correlation between functional activity of the brain tissue and structural-functional characteristics of the vascular system after sensory deprivation by the removal of whiskers in newborn animals were studied in nembutal-anaesthetized rats in comparison to the animals under d-tubocurarine with local anesthesia. It has been shown that there are major changes of EP parameters and ECoG in the sensory-deprived brain area and diminution of brain cortex thickness. Changes in the vascular system are mainly structural, what are revealed as disorganization in angioarchitecture of radial arteries. At the same time, differences in the blood circulation intensity are found in d-tubocurarine animals only. The largest volume of the local blood circulation is observed in intact hemisphere of sensory-deprived animal. Thus, it can be concluded that sensory-deprived model is the alternative to the ischemia model. This model can be used in studies of physiology of brain blood circulation, and the "structure function" correlation, in particular. PMID- 1302719 TI - [The normal distribution of oxygen tension on the surface of the brain radial arterioles and in their surrounding tissues and under normobaric hyperoxia]. AB - The pO2 on the arterioles' wall was shown to depend on the diameter of the vessels under study in rats. In normoxia, the pO2 tissue gradients are small and do not depend on the vessel diameter, whereas in hyperoxia a sharp drop of the tissue pO2 occurs at some distance from the vessel and the dependence of the pO2 on the arteriole diameter can be registered practically in all the sites of measuring. Radical arterioles and adjacent tissues of the brain cortex were shown to be most affected by a high arterial pO2 in hyperoxemia. PMID- 1302720 TI - [The euthyroid sick syndrome]. PMID- 1302721 TI - [The therapeutic advances in adult acute nonlymphoblastic leukemia. The experience at the Hospital de Especialidades of the Centro Medico Nacional Siglo XXI]. AB - Acute adult nonlymphoblastic leukemia (ANLL) involves a large group of diseases which originate in an abnormal process of differentiation of the hematopoietic stem cell. This paper analyses the historical background of such a group of malignant hemopathies, current criteria to perform the diagnosis and also the most important therapies used in both the stage of remission induction and the period following this stage (post-remission status). In this context, the therapeutic achievements that have had place during the last two decades at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI are analyzed. PMID- 1302722 TI - [Advances in the treatment of aplastic anemia]. AB - The purpose of this paper is to describe the current advances in the pathogenesis, classification and treatment of acquired aplastic anemia (AA). The therapeutical experience obtained at the Servicio de Hematologia, Centro Medico Nacional, Siglo XXI is described. Bone marrow transplantation is the first choice therapy for severe AA. This procedure succeeds in obtaining complete remission in nearly 80% of the cases. Nevertheless, few patients are eligible for such therapy, consequently other treatments should be considered. In this context some immunosuppressive therapies such as antilymphocyte globulin had shown to produce favorable responses in 60% of the patients. In addition, androgens and immunosuppressive drugs like methylprednisolone bolus and cyclosporin A do not have a definitive place in severe AA. Finally, it is important to describe the experience with lymphocytapheresis, a new procedure, that decreases the immunological response against the normal hematopoiesis by removing the population of T-lymphocytes inducing complete remission in a few patients. PMID- 1302723 TI - [Acute pancreatitis. The classification of its severity by dynamic pancreatography and the results of surgical treatment]. AB - In acute pancreatitis determination of glandular necrosis has been difficult because of the lack of an objective method; with dynamic enhanced tomography (bolus injection of contrast media) we have reasonably classify 28 patients with acute pancreatitis. With this technique 5 grades of sequelae of acute pancreatitis are identified: I. Non complicated acute pancreatitis; II. pancreatic abscess: III. peripancreatic necrosis; IV. less than 50% pancreatic necrosis and V. more than 50% pancreatic necrosis. A 100% correlation was found between tomography and surgical findings. This is the first report in Mexico of this method to identify pancreatic or peripancreatic necrosis; we also present the surgical results with a programmed pancreatic debridation; mortality has decreased form 80 to 31.9% in our hospital in recent years. PMID- 1302724 TI - [Cardiac myxoma. A report of 23 cases]. AB - Twenty-three cases of cardiac myxoma are reviewed during a period of 11 years. Seventeen patients were females and 6 males with an average age of 36 years. All patients were symptomatic for an average period of time of 4 months. Dyspnea was the main symptom (91%), congestive heart failure (52%), murmurs (74%), atypical chest pain (65%), palpitations (52%), constitutional manifestation (48%), congestive heart failure (36%), embolic events (23%) and ventricular tachycardia as a first manifestation of a right ventricular myxoma in one case (4.5). In all patients the diagnosis of cardiac tumor was made during life. Among they, in 83%, by echocardiogram, 14%, by cardiac catheterization, and in one case (4.5%) with both methods. Seventy percent were located in the left atrium, 18% in the right atrium, 9% in the right ventricule and 4.5% to both right cavities. Two patients died while waiting surgery, one due to pulmonary emboli and another due to refractory congestive heart failure. In all 21 patients who were sent to surgery a direct correlation was seen with the echocardiographic findings. All 23 patients had a confirmatory histopathological diagnosis. There were no surgical deaths. Excision of the tumor resulted in marked symptomatic improvement. The follow up by echocardiography showed that surgery has been curative with no recurrence up till now. We consider that this entity, that is capable to simulate multiple cardiovascular diseases must be removed surgically once it has been diagnosed in order to avoid fatal complications. PMID- 1302725 TI - [Immunosuppression and blood transfusions in patients with a kidney transplant]. AB - 94 patients with renal allograft from a living related donor were studied in three different groups: 1 Patients with identical histocompatibility (n-32), treated with prednisone (PDN) and azathioprine (Aza); 2 Haploidentical patients (34) who received PDN, Aza and cyclosporine (CsA); 3 Haploidentical patients (28) who previous to the transplantation received specific donor blood transfusions and Aza/PDN after the transplantation. The survival for the patient and the graft after five years was 100% and 96% in group 1; 97% y 89% in group 2 and 82% and 72% in group 3. Five patients in group 1 received CsA also. There was no mortality in group 1, while there were one death in group 2 and two more in group 3. There was no significant difference between CsA and Blood transfusions in the patients and grafts survival. PMID- 1302726 TI - [The evaluation of the kidney transplant patient by nuclear medicine technics]. AB - In Mexico, approximately between 200 to 250 patients received a renal transplantation each year. Immediately after the surgical procedure it is important to evaluate the function of the transplanted kidney. Because some complications may arise mainly with unspecific symptoms which often produce oliguria, high levels of serum creatinine, fever and pain at the site of the graft. In this paper we report the nuclear medicine methodology, which we use in the diagnostic evaluation of this patients. These methods are highly specific and provide useful quantitative and qualitative information about these morphology and the function of the transplanted kidney. PMID- 1302727 TI - [Extracorporeal lithotripsy in children]. AB - 14 patients of pediatric age with renal and ureteral calculi were treated with extracorporeal shock wave lithotripsy (Piezolith 2300). Three of the 14 patients had bilateral renal calculi. There were nine male and five female patients with an average age of 9.7 years. Most of the calculi were the renal pelvis. four calculi were smaller than 10 mm, 12 were between 10 and 20 mm and one was a partial staghorn calculi. A double "J" stent way placed in two patients, one with an ureterostomy and another with a partial staghorn calculi. The average number of shock waves received for patient was 4275 with an average voltage of 582 bars. Only 2 patients (16.6%) required sedation, six patients (47%) required more than one session of lithotripsy. The results at 3 months showed that 71.4% of the patients were free of stones. Hematuria was present in all the patients, hyperthermia greater than 38 degrees C and renal colic were present in 21.4% of the cases, two patients with retained ureteral calculi were rendered stone free by endoscopic procedures. In conclusion our results are similar to those reported in the world literature. The use of ultrasound for stone localization prevents unnecessary radiation of the children, and finally with the machine employed most of the treatments can be performed without anesthesia. PMID- 1302728 TI - [The correction of metabolic acidosis by the instillation of 0.1N sodium hydroxide in an experimental model]. AB - The critically ill patient, during the natural course of the disease often presents acid-base disturbances acidosis being the most common metabolic problem. Sodium bicarbonate has been used, for its correction but due to complications its use is restricted. In the present experimental study, mixed race dogs were artificially induced metabolic acidosis with in chloride acid. Arterial and venous blood gases were determined. Afterwards 0.1N sodium hydroxide was administered in the same amount statistically demonstrating modifications, in the pH values, as well as an excess of arterial and venous base which indicates the possibility of using this substance in humans to correct metabolic acidosis. PMID- 1302729 TI - [Autoimmune disease of the inner ear]. PMID- 1302730 TI - [The debridement of submandibular abscesses under locoregional block]. AB - The efficiency of analgesic block of the inferior alveolar, auriculotemporal, lingual, buccal and superficial cervical plexus in patients requires debridement of unilateral submandibular abscess has been investigated. The technique was significantly more useful (p < 0.001) when compared with other analgesic block techniques utilized in these cases. This treatment can be performed in any medical office with minimal resources and be of use as an alternative for general anesthesia. PMID- 1302731 TI - [The deterioration of cognitive functions in patients with dementia (a study of 18 cases)]. AB - It appears that general intelligence, memory, and conceptual reasoning, and others are impaired in dementia. As previously noted, in general there is said to be evidence of apraxia, or agnosia until the dementia is quite severe, unlike, for example, Alzheimer's disease. A number of questions, however, remain unanswered. PMID- 1302732 TI - [Acute respiratory insufficiency]. PMID- 1302733 TI - [The somatostatin analog SMA (201-995) as adjuvant treatment in patients with external fistulae of the digestive system]. AB - Six patients with gastrointestinal fistulae treated with a potent inhibitor of gastrointestinal hormones, the somatostatin analogue SMS 201-995 are reported. All patients had severe intraabdominal diseases and underwent a mean of 3.5 surgery procedures during their hospital stay. When the patients were analyzed individually a mean reduction of 42.5% (P < 0.050 of basal fistulae output was observed after treatment. In three patients the fistulae closed after seven and ten days of treatment with the analogue; the other three patients died after a protracted hospital stay which included multiple admissions to the Intensive Care Unit. When the output of all fistulae treated where analyzed together it showed a tendency to decrease, but it didn't reach statistical significance. PMID- 1302734 TI - [120 biopsies of pituitary adenomas studied by immunohistochemistry and electron microscopy. A clinico-pathological correlation]. AB - Study of biopsies from 120 pituitary adenomas from the Hospital de Especialidades, Centro Medico Nacional, and the Hospital 20 de Noviembre, ISSSTE, were studied over a period of 55 months. 70 cases were female and 50 male. Ages varied between 18 and 67 years of age (with an average of 31 years). Histologically 41 tumors were chromophobes, 34 acidophilic, 37 mixed and 8 basophilic. 101 patients were operated by trans-sphenoidal (84.5%) and 19 were operated (15.5%) by trans-cranial approaches. 99 tumors were macroadenomas (81.1%) and 21 were microadenomas (18.9%). More than one hormone was found in the cytoplasm of 69 adenomas, although only 20 fulfilled the criteria of being plurihormonal. Those adenomas classified as "non-functional", mostly produced glycoprotein hormones corresponding to oncocytomas and null cell adenomas, from an ultrastructural point of view. 85 patients developed different degrees of visual impairment, with 30 tumoral relapses, of which 10 received radiotherapy. 40 adenomas produced prolactin, although only 29 patients developed clinical signs of hyperprolactinemia; 38 tumors contained growth hormone, of which only 25 had acromegaly; 8 tumors contained ACTH in the cytoplasm, although only 7 developed Cushing's Syndrome and 57 patients (47.5%) were classified as nonfunctional and did not show any endocrinological data. All the cases are studied with a light microscope, electron microscope, and they were all submitted to a complete set of adenohypophyseal hormone with immunoperoxidase technique. PMID- 1302735 TI - [A guide for the study and treatment of the cadaver donor of organs for transplant]. PMID- 1302736 TI - [The use of computers in medical emergency services]. AB - Computers are being used successfully more often, in a number of medical facilities and specific medical care processes. Hospital emergency services have been including computer-assisted systems in solving a diversity of issues on administration, medical care delivery, research and teaching. An analysis is made about the possibilities of employment of computer-assisted information systems health administrative research in a continuous admission ward for non-elective patients to a tertiary-level care hospital, with its particular functional features. PMID- 1302738 TI - [Sexually transmitted diseases. Their diagnosis and treatment]. PMID- 1302737 TI - [Measles]. PMID- 1302739 TI - [The usefulness of determining cardiac myoglobin and myosin in the diagnosis of cardiac ischemia]. PMID- 1302740 TI - [Laparoscopic cholecystectomy]. PMID- 1302741 TI - [The serological exam for the human immunodeficiency virus (HIV) as part of the premarital exams]. AB - Due to the presence of the acquired immune deficiency syndrome (AIDS), it has been frequently stated, by several segments of the society, that mandatory human immunodeficiency virus (HIV) testing as premarital requirement is useful for AIDS prevention. The usefulness of these tests among general population are discussed, as well as some problems for its eventual implementation, concluding that this screening procedure is impractical, inefficient and expensive as a public health measure. The overall HIV prevalence in Mexico is very low (4 per 10,000), therefore, a person from this population with a positive screening test, has a slight chance of being truly infected (16%), in other words, screening tests have a low positive predictive value in general population. Conversely, having a negative screening test, predicts this state accurately (negative predictive value greater than 99%). Several problems arise when HIV screening tests are applied: logistics, for example avoidance of the tests, economic, ethic, and human rights problems, among others. It is concluded that mandatory HIV screening tests are not cost-efficient and that there are other options, for instance education, which would imply better changes for HIV prevention. PMID- 1302742 TI - [The epidemiological panorama of cancer in Mexico, 1987]. AB - The mortality, incidence, morbidity, partial data and opportune detection, of the main cancer types were reviewed from de information register corresponding to 1987, to analyze the epidemiological panorama of cancer in Mexico. The main causes of death in women were cervix uterine, breast, stomach and lung carcinomas, leukemias and lymphomas; and in men were lung, gastric, prostate, leukemias and lymphomas. The most frequent localization of women's new cancer cases were cervix uterus, breast, ovary, lymphoma, thyroid gland and endometrium; and in men were prostate, lymphoma, stomach, leukemia and lung. In according to tendencies about the main death rates in Mexico, we estimate that 55.3 by 100.00 inhabitants will be the rate of cancer deaths in the year 2000, numerical character virtually bigger considering demographic variation like human life's hope and increase population with cancer risk. PMID- 1302743 TI - [Neurosciences and medicine]. PMID- 1302744 TI - Denial in terminal illness: to intervene or not to intervene. AB - This research examined effects of psychosocial intervention on denial-related coping ability in terminally ill cancer patients. Most patients considered deniers were seen using interpersonal denial in the service of preserving relationships important to them. Denial use as a result of intrapsychic impoverishment was seen infrequently. Twenty-four patients with various terminal cancers were assigned to either an experimental (n = 13) or a control (n = 11) group. A pretest versus posttest multifactorial analysis of variance model was used. Experimental subjects received a structured psychosocial intervention just before posttest. Results showed that, as predicted, interpersonal deniers in the experimental group had a statistically significant (p < .005) decrease in denial scores at posttest, whereas denial scores increased in the control group. Data indicate that, in the absence of psychological dysfunction, patients using interpersonal denial may respond favorably to sensitive psychosocial intervention. Still others may benefit only after they have had sufficient time to muster adaptive coping strategies. Areas for further research are suggested. PMID- 1302745 TI - The attitudes of beginning nursing and medical students toward care of dying patients: a preliminary study. AB - The attitudes of entering classes of nursing and medical students toward the care of dying patients were compared using a self-administered instrument designed for the study measuring aversive and attractive components of these attitudes. Both groups exhibited similar aversive attitude items: Talking About Death elicited the most negative scores, General Interaction was slightly less negative, and Touching was the least negative. Among the attractive items, medical students were more positive on the Professional Challenge subscale, while the nursing students were more positive on the Personal Satisfaction subscale. PMID- 1302746 TI - Grieving men: thoughts, feelings, and behaviors following deaths of wives. AB - Despite the growing body of literature on bereavement, grief, and mourning, little attention has been given to the impact of bereavement on men. This is particularly true for studies on the impact of death of spouse on the survivor. Using in-depth interviews, we explored the thoughts, feelings, and behaviors of twenty men following the deaths of their wives. The findings do not support prevailing assumptions that men are less likely to be emotionally involved in the conjugal relationship and, thus, less likely to grieve than women; or, if emotionally involved, less likely to experience grief. This research suggests that men may be emotionally involved in the conjugal relationship and that the death of a wife may evoke intense feelings. The majority of the men in this study both hurt and knew they hurt. What they did not do was to reach out to others for help. This finding has important implications for bereavement program development. PMID- 1302747 TI - Providing spiritual support: a job for all hospice professionals. AB - This research examines spirituality as an aspect of professional practice. A questionnaire on spirituality was sent in 1991 to the hospice directors in New York, New Jersey, and Pennsylvania. The findings strongly indicate that spirituality is important in the hospice setting and plays a prominent role in the treatment of patients. Also, hospice programs were found to be supportive of the spiritual component of care. The spiritual approaches used by the respondents were the more traditionally religious ones such as listening to the patient talk about God or referring to clergy. Approaches such as meditation or guided imagery, which are not necessarily related to religion, were used less frequently. Clergy in the study placed greater importance on spirituality in hospice work and used more traditionally religious approaches than did non clergy. While some professional caregivers choose to leave spiritual matters to clergy, the findings reveal that many non-clergy hospice professionals are assisting patients with spiritual concerns. PMID- 1302748 TI - Bronchial hyperreactivity in chronic obstructive airways disease. PMID- 1302749 TI - A study of bronchial reactivity in relation to baseline pulmonary functions in patients with chronic obstructive lung disease. AB - Baseline bronchial reactivity was studied in 36 patients with chronic obstructive lung disease (COLD) and 20 normal healthy controls using the inhalational histamine challenge test. Using a cut off PD20 dose of 0.195 mg of histamine, 83.3% patients of COLD demonstrated bronchial hyper-reactivity. Presence of bronchial reactivity correlated significantly with the baseline FEV1, FEF25-75 and the ratio FEV1/FVC (p = 0.0019, 0.00001 and 0.008) respectively. Thus, bronchial reactivity in subjects with COLD correlates most significantly with the maximum mid-expiratory flow rate (FEF25-75). PMID- 1302750 TI - Efficacy of stimuliv, an indigenous compound formulation, against hepatotoxicity of antitubercular drugs--a double blind study. AB - Anti-tubercular drugs are known to cause hepatotoxicity, which may lead to noncompliance to drug therapy. Stimuliv, an indigenous compound formulation, is reported to be useful in liver disorders. Efficacy of prophylactic administration of stimuliv against anti-tubercular drugs-induced hepatotoxicity was studied in this double blind randomized clinical trial. One hundred and forty-five newly diagnosed patients of tuberculosis were included in the study. Out of these, sixty three patients were treated with stimuliv (2 tablets thrice daily), sixty received the placebo, while twenty-two dropped out of the study. The patients were assessed clinically and biochemically at two-week intervals over a period of two months. In stimuliv-treated group, the incidence and severity of hepatotoxicity was significantly less (p < 0.05) as compared to placebo-treated group. In addition, patients treated with stimuliv had better appetite and weight gain. Stimuliv treatment may be recommended in newly diagnosed adult patients of tuberculosis. PMID- 1302751 TI - Dermatoglyphics in nasobronchial allergic disorders. AB - Fifty persons having nasobronchial allergy diagnosed by a positive skin test were compared with age and sex matched normal individuals for dermatoglyphic palmer patterns. The palmer prints were obtained on white art paper using Kores duplicating ink. In female patients, total number of whorls was less, more so on digit IV of left hand. Digit V of right hand had low frequency of ulnar loops, the d-t ridge count was low. In male patients, ulnar loops were less frequent on digit III of right hand. Total finger ridge count was less in both sexes. High frequency of arches was observed in female patients and in total. Digit V of left hand in females and in total patients revealed high frequency of arches. a-b ridge count was high in males and in total patients. PMID- 1302752 TI - Pulmonary function tests in healthy male Punjabi children [10-19 years of age]. AB - We performed spirometry on 177 male healthy children from Patiala, North India between 10 to 19 years age. The best fit regression equations for different functions were determined for each parameter. A linear relationship of lung function was observed with age, height, weight and BSA. Our results have been higher than the South Indian studies but closer to other North Indian studies. Similar comparison with western studies reveals that their subjects have higher lung function values than our subjects. It is clear that grossly erroneous conclusions may be reached unless prediction equations for lung function tests for a given ethnic group are derived from studies upon the same ethnic group. PMID- 1302753 TI - Factors associated with isolation of pathogenic bacteria from sputum of patients with acute bronchospasm. AB - Patients with obstructive airways disease (asthma and chronic obstructive airways disease) with an acute exacerbation of symptoms were studied. Those requiring hospitalization were chosen to study the pattern of respiratory pathogens isolated on a supervised sputum culture. Certain variables were studied in a case control design to determine an association with culture positivity. PMID- 1302754 TI - Pulmonary alveolar microlithiasis--report of three cases with pulmonary function and exercise studies. AB - Pulmonary alveolar microlithiasis is a rare disease involving accumulation of calcific concretions in the alveoli of the lungs. Three cases of this disease are reported with their varying and unusual clinical features. Radiologic studies demonstrated presence of diffuse calcific densities in the lungs with varying degrees of emphysematous changes. Bone scans showed diffuse uptake of the tracer in the lungs. Pulmonary functions showed hyperinflation and small airways dysfunction in one case besides the presence of restrictive ventilatory defect. Exercise studies demonstrated arterial oxygen desaturation on exercise. PMID- 1302755 TI - Digital clubbing in sarcoidosis. AB - We present two cases with a rare association of sarcoidosis and clubbing. Therapy with prednisolone could not control the progress of interstitial fibrosis nor could clubbing be reversed. Both patients expired 5-1/2 years after diagnosis which suggests that clubbing, when present in sarcoidosis, may signify an unfavourable prognosis. PMID- 1302756 TI - Giant emphysematous bullae of the lung. AB - Emphysematous bullae may at times assume large proportions. We report a case of symptomatic giant bullae in a female which were removed surgically. The relevant literature has also been reviewed. PMID- 1302757 TI - Tropical pulmonary eosinophilia presenting as eosinophilic pleural effusion. AB - A case of tropical pulmonary eosinophilia presenting as an eosinophilic pleural effusion is reported. The condition resolved by treatment with diethylcarbamazine. The patient has been well during the two year follow-up period. PMID- 1302758 TI - Hepatitis due to anti-tuberculous drugs. PMID- 1302759 TI - Sequential pattern formation in a model for skin morphogenesis. AB - During morphogenesis regular patterns often develop behind a frontier of pattern formation which travels across the prospective tissue. Here the authors consider the propagating patterns exhibited in a two-dimensional domain by a tissue interaction mechanochemical model for skin pattern formation. It is shown that the model can exhibit travelling waves of complex spatial pattern formation. Two alternative mechanisms that can produce such sequential patterning are presented. In particular, it is demonstrated that the specification of a simple quasi-one dimensional pattern is all that is required to determine a complex two dimensional pattern. Finally, the model solutions are related to actual pattern propagation during chick feather primordia initiation. PMID- 1302760 TI - From stripes to spots: prepatterns which can be produced in the skin by a reaction-diffusion system. AB - A key question in the area of spatial pattern formation in developmental biology is: how do groups of cells in a homogeneous tissue suddenly differentiate along entirely different developmental paths compared to neighbouring cells? Although experiments are now beginning to provide answers to this question, the mechanisms responsible for the development of repeated or periodic structures and spatial patterns, e.g., hair follicles and pigmentation patterns, are still unknown. Theoretical biologists and applied mathematicians have suggested various prepattern mechanisms as the primary cause of repeated or periodic spatial patterns. A class of biochemical reactions referred to here as reaction-diffusion (RD) systems, having the capacity to spontaneously generate stable stationary wavelike spatial patterns (Turing, 1952), has been suggested as a possible prepattern mechanisms, e.g., during hair follicle initiation and development (Nagorcka, 1989), and pigmentation patterns (Murray, 1989). Spatial patterns arising during development of the vertebrate skin are frequently complex. Spatial patterns in the skin can be seen to vary within an individual from one region of the skin to another. One pattern change commonly observed across the skin is from stripes to spots. An RD system is defined which is able to generate different spatial patterns depending on the value of a single parameter. The parameter varied controls the transport of the chemical components of the RD system across the basement membrane separating the epidermis and dermis. The patterns produced range from stripes to an irregular array of spots. Not only are different patterns produced, but a different time sequence of prepatterns is expected to arise in the different skin regions depending on whether the first prepattern in an array of spots or stripes. As a consequence it is possible to account for hair follicle initiation in the hair-bearing regions of the mammalian skin as well as the sequence of events required for the formation of dermatoglyphics in the volar regions. PMID- 1302761 TI - Modelling trypanosomiasis prevalence and periodic epidemics and epizootics. AB - Existing mathematical models of trypanosomiasis epidemiology and epizootiology are extended by including some relevant biology of the disease vector, the tsetse fly. Rickettsia-like organisms, or RLO, are a vertically transmitted symbiont of tsetse, which confer an increased susceptibility to trypanosomiasis infection. Tsetse populations are also limited by density-dependent starvation. Modelling leads to the prediction of a stable dimorphism with a fraction of tsetse possessing RLO. The equilibrium prevalence of trypanosomiasis in the vertebrate hosts is no longer in RLO models determined simply by such traditional parameters as vectorial capacity. Only the RLO-positive tsetse carry infection, and their number is itself regulated by trypanosomiasis prevalence. The result of a naive model is that controlling tsetse numbers does not decrease prevalence until all tsetse are RLO-positive. However, under the density-dependent starvation model derived in this paper, the relative mortality of RLO-positive flies is greater at lower tsetse numbers. This tips the balance towards lower equilibrium prevalence of trypanosomiasis as tsetse numbers are decreased. The presence of RLO also gives rise to long-term oscillations in trypanosomiasis prevalence in humans and animals. However, when another mechanism that can also cause periodic epizootics (of shorter periodicity) is included, namely host immunity, the two epizootic processes combine to produce periodic epizootics (and therefore epidemics) at a single frequency. There are two decaying modes, one in which the tsetse population size quickly reaches equilibrium in a few weeks, and a second very slowly decaying mode in which host immunity and RLO effects interact. The equilibrium reached is shown to be asymptotically stable. In view of the seeming importance of RLO in trypanosomiasis epidemiology, it is important that field biologists enable RLO models to be validated by measuring the proportion of tsetse with RLO, in conjunction with vector density and trypanosomiasis prevalence and incidence in tsetse and vertebrate hosts. PMID- 1302762 TI - On the Penrose hypothesis on fingerprint patterns. AB - Penrose hypothesized that fingerprint patterns such as loops, whorls, etc. are formed by ridges corresponding to the lines of curvature of the skin of the embryo at the time when the ridges were being formed. Under this hypothesis, Smith (1979) has shown analytically how some patterns emerge. In this paper it is shown that (i) Smith's differential equation has an exact solution and (ii) the extension given here supplies the remaining important patterns. PMID- 1302763 TI - Evaluation of dose-related pharmacokinetics and pharmacodynamics of prednisolone in man. AB - The pharmacokinetics and pharmacodynamics of prednisolone were evaluated in normal male volunteers. Seven subjects completed 3 phases: 16.4- and 49.2-mg iv prednisolone, and a phase with no drug to assess baseline responses. Plasma concentrations of prednisolone and urine concentrations of prednisolone and 5 metabolites were assayed by HPLC. Protein binding of prednisolone was measured by ultrafiltration. The polyexponential disposition of free and total plasma prednisolone were evaluated and apparent parameters were compared between doses. Suppression of plasma cortisol and alterations in blood basophil and helper-T cell trafficking were used as pharmacodynamic indices. Pharmacodynamic models were used to relate total or free plasma prednisolone concentrations to each of these effects generating response parameters and IC50 (50% inhibitory) concentrations common to both doses. The pharmacokinetics of total drug were comparable to previous findings with CL and Vss increasing with dose. Free prednisolone exhibited slight capacity-limited elimination and distribution as CL and Vss decreased with the larger dose. Pharmacodynamic models jointly fitting all three phases characterized the suppression/trafficking phenomena equally well with use of total or free drug concentrations. In each case the models provided realistic values of parameters relating to steroid sensitivity--in particular IC50--and to the underlying physiology of the affected systems. This study comprehensively elucidates the complexities of prednisolone pharmacokinetics and demonstrates how plasma concentration--time profiles of total or free prednisolone can be utilized for evaluation of prednisolone pharmacodynamics. PMID- 1302764 TI - A physiologically based pharmacokinetic model for nicotine and cotinine in man. AB - Physiologically based pharmacokinetic (PBPK) models have been developed describing the disposition kinetics of nicotine and its major metabolite, cotinine, in man. Separate 9-compartment, flow-limited PBPK models were initially created for nicotine and cotinine. The physiological basis for compartment designation and parameter selection has been provided; chemical-specific tissue to-blood partition coefficients and elimination rates were derived from published human and animal data. The individual models were tested through simulations of published studies of nicotine and cotinine infusions in man using similar dosing protocols to those reported. Each model adequately predicted the time course of nicotine or cotinine concentrations in the blood and urine following the administration of nicotine or cotinine. These individual models were then linked through the liver compartments to form a nicotine-cotinine model capable of predicting the metabolic production and disposition of cotinine from administered nicotine. The potential for integrating this functional PBPK model with an appropriate pharmacodynamic model for the characterization of nicotine's physiological effects is discussed. PMID- 1302765 TI - Application of semilinear canonical correlation to the measurement of opioid drug effect. AB - To examine the relationship between the electroencephalograph (EEG) and plasma opioid concentration, one would like to collapse the high-dimensional EEG signal into a univariate quantity. Such a simplification of the EEG is desirable because a univariate quantity can be modeled using standard nonlinear regression techniques, and because most of the information in the EEG is redundant or unrelated to drug concentration. In previous studies of the EEG response to opioids, the manner in which a univariate component was extracted from the EEG was ad hoc. In this paper, this extraction was performed optimally using a new statistical technique, semilinear canonical correlation. Data from 15 patients who received an intravenous infusion of the semisynthetic opioid alfentanil were analyzed. The components of the EEG that were nearly maximally correlated with plasma drug concentration were found, based on a standard pharmacokinetic pharmacodynamic model. Two new EEG components were produced from the powers in the frequency spectrum of the EEG: a weighted sum of the logarithms of the powers, and a weighted sum of the powers expressed as percentages of the total power. These components both had a median R2 of 0.84, compared to median R2s ranging from 0.37 to 0.83 for five commonly used ad hoc EEG components. The new components also had less variability in R2 between subjects. PMID- 1302766 TI - Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow. AB - Mass balance pharmacokinetics, with simultaneous blood sampling from an artery and the internal jugular vein, was used to characterize the cerebral uptake of ketamine, norketamine, and midazolam in normoventilated pigs. Intravenous injections of ketamine or midazolam decreased the cerebral blood flow (CBF) by one third, as measured by intermittent 133Xe washout. By means of pharmacodynamic models, the effects on the CBF could be predicted from the arterial drug concentrations. The high-resolution CBF vs. time curves thus generated allowed the calculation of cerebral drug levels from arterio-venous concentration gradients in spite of a continuously changing regional blood flow. By their effects on the CBF, ketamine and midazolam decrease their own rate of transport to the brain, the immediate 30-35% drops in CBF giving similar reductions in initial net influx of drug. Physiological pharmacokinetic models assuming a constant regional blood flow are therefore not appropriate. Under clinical conditions, the CBF is determined mainly by the effects of the anesthetics and by the arterial CO2 tension. CBF changes in either direction influence the transport of drugs to the brain and may consequently result in impaired or exaggerated drug effects. PMID- 1302767 TI - Evaluation of Bayesian estimation in comparison to NONMEM for population pharmacokinetic data analysis: application to pefloxacin in intensive care unit patients. AB - The pharmacokinetics of pefloxacin (PF) were investigated in a population of 74 intensive care unit patients receiving 400 mg bid as 1-hr infusion using (i) Bayesian estimation (BE) of individual patient parameters followed by multiple linear regression (MLR) analysis and (ii) NONMEM analysis. The data consisted of 3 to 9 PF plasma levels per patient measured over 1 to 3 dosage intervals (total 113) according to four different limited (suboptimal) sampling 3-point protocols. Twenty-nine covariates (including 15 comedications) were considered to explain the interpatient variability. Predicted PF CL for a patient with median covariates values was similar in both BE/MLR and NONMEM analysis (4.02 and 3.92 L/hr, respectively). Bilirubin level and age were identified as the major determinants of PF CL by both approaches with similar predicted magnitude of effects (about 40 and 30% decrease of median CL, respectively). Confounding effects were observed between creatinine clearance (26% decrease of PF CL in the BE/MLR model), simplified acute physiology score (a global score based on 14 biological and clinical variables) (18% decrease of median CL in the NONMEM model) and age (entered in both models) which were highly correlated in our data base. However, both models predicted similar PF CL for actual subpopulations by using actual covariate values. Finally, the NONMEM analysis allowed identification of an effect of weight on CL (decrease of CL for weight < 65 kg) whereas the BE/MLR analysis predicted an increase of CL in patients treated with phenobarbital. In conclusion, both approaches allowed identification of the major risk factors of PF pharmacokinetics in ICU patients. Their potential use at different stages of drug development is discussed. PMID- 1302768 TI - The impact of AIDS on blood transfusion services in South Africa. AB - The escalating incidence of AIDS in the African population will result in the occurrence of substantial numbers of transfusion-transmitted cases of AIDS. This can theoretically be controlled by using only blood from low-risk groups for the transfusion of cellular products, and using blood derived from the high-risk section of the community only for the production of plasma-derived products that can be virally inactivated. In the South Africa context, with its dichotomous first world and third world population, this will require certain steps which contravene various norms generally accepted by the blood transfusion discipline in Western Europe. PMID- 1302769 TI - Sexual misuse of children by family members: the dynamics of a complex problem. AB - Studies suggest that, in the United States, as many as one of every three or four children have been or will be sexually misused, but most of these episodes will never be reported. Many of the victims are abused by members of their own family. Why this abuse occurs and why it often remains undisclosed are explored in this article. The types of abuse and the situational aspects that give rise to its occurrence are analysed both in terms of participants (offenders, victims and other family members) and in terms of form (incestuous relationships within the home and outside exploitation). Possible solutions to this complex problem are also considered with the realization that only by first understanding the many factors that create and reinforce the patterns of abuse, will we be able successfully to address this common and most disturbing matter. PMID- 1302770 TI - Doctors' death experience and attitudes towards death, euthanasia and informing terminal patients. AB - In daily practice physicians are professionally obliged to interpret ethical precepts and laws in emergency situations under extreme pressure when resuscitation measures leave little or no time to consider deontological issues. The extent to which extraprofessional experiences influence physicians' attitudes towards death and terminal patients is a difficult issue to approach with precision. The purpose of this study was to analyse the influence of some personal biographical circumstances on physicians' attitudes towards death and terminal patients. A total of 153 doctors ranging in age from 22 to 77 years (mean 38.24; SD 13.08) were randomly chosen. Physicians, as an integral part of society, cannot be expected to be immune to the influences which mould our attitudes. We suggest that young physicians and medical students should receive information and training aimed at equipping them to face death and dying patients. PMID- 1302771 TI - Legal and economic challenges to personal autonomy: a view from the United States of America. AB - Steadily and surely, commonly accepted notions of individual rights and the place of the individual in society are subject to increasing scrutiny. This article critically analyses legal and economic parameters which directly affect both personal autonomy and the role of government, interpreted through its higher level state and federal judiciary, on the public. PMID- 1302772 TI - Genetic testing and insurance. AB - To what extent should insurance companies be allowed to collect genetic data on persons seeking insurance cover? This question has evoked public debate in the Netherlands. In March 1990 a temporary agreement was reached between insurers and the government. This article discusses the arguments underlying this agreement and in particular the question whether genetic information should have the same status under the law as other medical information. PMID- 1302773 TI - Towards a new legal regulation of medically assisted reproduction: the Austrian approach. AB - At long last Austria, too, has come round to a more or less final draft law on assisted reproduction (at the third attempt). It portrays a compromise of liberal and conservative views, which in some points has led to inconsistencies in its logical conception. The donation of semen, for instance, will be permitted, whereas ova donation will be strictly forbidden, the law will allow AID and at the same time prohibit heterologous IVF. The leading principles throughout this law, viz human dignity, procreative autonomy, and the best interests of the child, undoubtedly vital in this context, are sometimes applied to justify regulations, for example, those that deny single women access to assisted reproduction, violating the principle of equality. In this respect, the draft law definitely does not bear a closer examination. PMID- 1302774 TI - Attitudes of physicians to medical malpractice litigation in Canada. AB - This article reports the results of a survey of the attitudes of medical practitioners in the Sudbury and Manitoulin Health District of Northern Ontario with respect to their experience of litigation alleging medical malpractice. The survey is part of a research project, funded by the Foundation for Legal Research, Montreal, investigating the extent to which the very high incidence of medical litigation in the United States of America is likely to spread to Canada. PMID- 1302775 TI - The legal status of the embryo in comparative perspective. AB - Almost all decisions with regard to allowing or forbidding research with and on the embryo as well as any other diagnostic invasion into the embryo depend on what kind and range of protection human life in this early stage of its development is or should be entitled to. This question is commonly referred to as that of the 'moral status' of the embryo or-with special regard to legal provisions and sanctions-as its 'legal status'. The answer to this fundamental question, however, is much debated and highly controversial, both nationally and internationally. Therefore professional and legal regulations range from the rather permissive (as in the new English Human Fertilization and Embryology Act of 1990) on the one hand to the total prohibition of embryo research or certain reproductive procedures on the other (as has recently been enacted by the German Embryo Protection Act of 1990). Thus, trying to reach consensus with regard to an embryo's legal/ethical right to protection is made all the more difficult because such an opinion is often, consciously or unconsciously, prejudiced by the desire to give researchers either more or less freedom of action, depending on one's point of view: Those who wish to see diagnostic or other experimental procedures with embryos facilitated, are inclined to deny their human quality from the very start. They base their arguments on the lack of individual personality in the preinidation phase of development, or simply on the fact that in many countries abortion is not illegal at that stage. Those who, on the contrary, find abortion as well as embryo research indefensible, believe their position well-founded by assuming that the embryo, from the time of fertilization, has the individuality and personality of a human being and thus is entitled to its own basic legal rights. Since to me neither of these extreme positions seems to be particularly cogent, I will try in this article to show the reasons for and consequences of adopting a middle course which neither leaves the embryo at free disposition nor bars any kind of diagnostic or other scientific invasion. PMID- 1302776 TI - Europe 1992: conflicts between European law and national health law. AB - In this article conflicts between European law and national health law are discussed. National laws are no longer immune against the radical changes which are taking place within the European Community. National authorities also are not free to organize health care and develop health laws in their own countries without taking into consideration the consequences of the European legislation. Rules and regulations are needed for the organization and structure of health care, and health law regulations and directives are required. They have to contain stipulations to ensure, in the 'Europe Without Frontiers' expected after 1992, solidarity between the sick and the healthy, among age groups and income groups, in partnerships and regions with great and little demand for and the supply of health care services. For a consistent system of rules and regulations, a synthesis of the principles of European law and the principles of health law is indispensable. PMID- 1302777 TI - Euthanasia, the right to die and the law in South Africa. AB - In this article euthanasia is defined and classified. Each of the classification is examined in relation to the relevant South African law as are the possible defences to criminal charges flowing from a euthanasia situation. Further, the validity of the so-called 'living will' is examined. While most declarations or bills of human rights seek to protect an individual's right to life, this article shows that an individual enjoys no right (from a human right point of view) enabling him to choose the time and condition of his death, irrespective of whether he is terminally ill. The reason for this negative attitude to euthanasia by society is considered. In conclusion it is observed that due to the plurality of society in South Africa, it will be no easy task for the legislature to pass acceptable laws regarding euthanasia, however limited. Finally, positive suggestions are made for the implementation of a valid 'living will'. PMID- 1302778 TI - Cooperation between experts in fitness proceedings. AB - The handling of the mentally ill offender involves the law as well as psychiatry and it is, therefore, essential that a good relationship exists between the jurist and the psychiatrist. The answering of questions of law by the courts needs the assistance and cooperation of mental health experts. This cooperation between the law and mental health professions is inevitable and necessary because the court is not an expert in the field of psychiatry. The duty of the psychiatric expert is to furnish the judge with necessary scientific criteria for testing the accuracy of the conclusions, so as to enable the court to form its own independent judgment by the application of these criteria to the facts proved in evidence. PMID- 1302779 TI - United Kingdom 'Crown' indemnity for medical negligence--an overview of the first 18 months of the new scheme. AB - This article describes the background to the introduction of 'Crown' indemnity and summarizes the operation of the scheme. It also makes clear the limited nature of the scheme and how it does not apply, for example, to independent contractors such as general medical and dental practitioners. Also described is the nature and operation of United Kingdom medical defence organizations such as the Medical Protection Society and the services which they continue to provide to medical and dental practitioners worldwide. Early indications suggest that the new government scheme is placing a very heavy financial burden on health authorities which already suffer from underfunding and tight budgetary control. PMID- 1302780 TI - Doctors' rights and patients' duties? AB - Currently, there is an increasing tendency to convert patients' rights into duties. At least three areas can be identified: The tendency of the health care provider to claim duties of the patient in the doctor-patient relationship; the trend to stipulate conditions when patients are in need of health care delivery; and the evolution towards the formulation of patients' legal duties when third party interests are involved. The societal tendencies to convert legal rights into legal duties, to require counter-services from the patient and to control patients' behaviour, limit patients' rights to self-determination and essential human rights in health care. Ultimately, intervention through legislation might be necessary. PMID- 1302781 TI - The doctor's duty of disclosure and excessive information liability. AB - This article critically examines the recent phenomenon of legal liability for so called excessive disclosure within the context of the informed consent doctrine. An attempt is made to formulate a set of workable principles to cater for both the doctor's dilemma and the patient's protection in over-information cases against the backdrop of the general principles of the doctor's duty to disclose. PMID- 1302782 TI - Mistreatment of the aged in the home environment in northern France: a year survey (1990). AB - As the percentage of the population which is aged increases in the developed countries, public health problems arise from the limited autonomy and physical or mental infirmity of the elderly. Cohabitation arrangements, often used to permit the elderly to stay at home, can give rise to conflict and the mistreatment of the aged. We analysed questionnaires distributed in 1990 to 25 home nursing units and two hospitals in a part of the northern region of France. Fifty-five observations of mistreatment were collected, 22 from hospital and 33 from home based inquiries. The types of mistreatment and the characteristics of the victims and perpetrators are detailed and discussed. Penal and legal aspects of mistreatment of the aged in France are discussed. PMID- 1302783 TI - The image of the insane in ancient Jewish lore. AB - This article considers the attitude towards the insane and insanity in ancient Jewish sources. In the Bible, the most famous case of a psychopathological personality is that of King Saul, who was plagued by 'an evil spirit'. Saul also raises the problematic connections between prophecy and frenzy. Madness and confusion of mind are mentioned among the biblical 'curses for disobedience'. In the Talmud, there is a detailed symptomatic evaluation of insanity, in the context of legal liability. It is well-known that some individuals are at times insane, otherwise sane and responsible, which is legally taken into careful consideration. The Jewish historian Josephus describes in his works several cases of psychiatric patients. The most impressive case is that of Jesus ben Ananias, a delirious maniac who announced the fall of Jerusalem while roaming about the streets of the city. It may be argued that no clear attitude of derision or ostracism towards insane patients can be found in ancient Jewish literature. 'The Lord preserves the fools' (Ps 116: 6). PMID- 1302784 TI - The medico-legal, social and ethical implications of surrogate parenthood. AB - Infertility has existed for thousands of years and treatment has evolved with the advance of medical science. Surrogate parenthood was effected previously by sexual intercourse, but AIH, AID and GIFT have rendered this practice obsolete. The terms surrogate mother, partial and full surrogacy are defined. Medico-legal, social and ethical arguments for and against surrogacy are discussed. References are made to varying national attitudes as to the desirability of legalizing surrogate parenthood and the implications for commissioning parents, the surrogate mother and adequate counselling are considered. PMID- 1302785 TI - Saying you're sorry in a litigious society. PMID- 1302786 TI - Effect of premedication on the changes of neuropeptide Y (NPY) in anesthesia. AB - Premedication is one of the popular techniques in anesthesia, not only for the decrease of side effects but also for the increase of actions. Clinically, we found that plasma neuropeptide Y-like immunoreactivity (NPY-IR) was lowered in patients who had received premedication. In rats, plasma NPY-IR was not modified by the intravenous injection of diazepam. Pethidine reduced the plasma NPY-IR level which could be reversed by naloxone. Direct inhibition of plasma NPY-IR through an activation of opioid receptors can thus be considered. To the cold stress stimulation, plasma NPY-IR was markedly raised. Diazepam reduced this stimulation-induced increase of plasma NPY-IR in a dose-dependent manner. Similar derivative of benzodiazepine produced an inhibition in a way following the potency as that to produce anxiolytic action. Also, this inhibition was reversed by PK11195, an antagonist of peripheral benzodiazepine receptors. Moreover, pain stimulated increase of plasma NPY-IR in rats was also reduced by pethidine. This action was totally reversed in the presence of naloxone, indicating the participation of opioid receptors in the process. The obtained results suggest that premedication of diazepam and/or pethidine has the ability to decrease plasma NPY-IR in animals. PMID- 1302787 TI - [Changes of blood viscosity in patients undergoing cardiac surgery during cardiopulmonary bypass]. AB - The patient undergoing open-heart surgery depends on hypothermia and cardiopulmonary bypass (CPB) to maintain organ perfusion during cardiac arrest. Increased blood viscosity during hypothermic CPB might be life-threatening, so hemodilution is imperative. Fourteen open-heart patients of ASA class II-III were included in this study. Pre- and intra-CPB viscosity changes were observed. Before CPB, 6 ml blood sample was drawn out from open-heart patients after systemic heparinization and another 6 ml blood sample was drawn out from the oxygenator after CPB was established. The hematocrit and relative viscosity of each sample in different temperatures were measured. The result revealed that as the temperature decreases, the viscosity of each sample increases apparently. As compared to the pre-CPB blood sample, the hematocrit of blood obtained intra-CPB decreases from 36.81 to 27.04, (p < 0.001), and the viscosity also decreases at all different temperatures (p < 0.001). Blood viscosity obtained at 37 degrees C pre-bypass is not statistically different from the sample at 25 degrees C during bypass. Obviously, increased viscosity due to hypothermia is buffered by hemodilution after using large amount of fluid as priming solution during CPB. Therefore, the hematocrit and viscosity remain within physiologic ranges. PMID- 1302788 TI - The sedative effect of intravenous injection of low dose midazolam during spinal anesthesia in cesarean section. AB - In a randomized blind study, we compared the neonate Apgar score, umbilical venous pH, incidence of maternal hypotension and intra-operative maternal discomfort in elective Cesarean section performed under spinal anesthesia in two groups of parturients with or without low dose midazolam as a sedative agent before the deliveries. Each group consisted of 20 parturients. Ninety percent of the mothers in the midazolam group fell asleep smoothly before the operations started. The neonates in the midazolam group were scored similar to saline control group on Apgar score and umbilical venous pH. The incidences of maternal hypotension during operation in both groups were 55%. However, the occurrence of intra-operative maternal discomfort was eleven fold more often in the saline control group. On the other hand, there existed a significant inverse correlation between uterine incision-delivery interval and Apgar score as well as umbilical venous pH. We concluded that low dose midazolam is a good sedative agent during spinal anesthesia in elective Cesarean section. It is also safe and effective even given before delivery. PMID- 1302789 TI - Is routine preanesthetic hemoglobin test necessary in minor pediatric surgery? AB - The value of preanesthetic assessment of anemia and analysis of the hemoglobin level prior to a minor pediatric surgery has been recently questioned in some reports. This study was to retrospectively analyse 8859 pediatric patients who underwent minor surgery in the period from January 1987 to December 1990 in our hospital. They were all ASA class I-II in physical status with age ranging from one month to 19 years. Those patients with their hemoglobin values determined at other laboratories or hospitals in spite of our recognition and those suspected of having an immune or oncologic disease were excluded from this study. The mean hemoglobin value of the patients under study was 12.99 +/- 0.82 g/dl. 0.62% of the patients (55) were found to have hemoglobin values less than 10 g/dl which were similar to the results obtained by Wood et al (0.7%) in 1981 and Roy et al (0.5%) in 1990. Among the 55 anemic patients, 41 (74.5%) were at the age between 2 to 4 months (within the physiologic anemic period of infancy). Sampling of blood for routine preanesthetic hemoglobin determination which caused discomfort and pain was often rejected by pediatric patients and struggle for escape also upset the children very much. Based on the results from our analysis, we suggest that in healthy pediatric patient scheduled for minor surgery routine hemoglobin test could be excluded. Hemoglobin test is selectively performed in a patient is anemic or under suspicious circumstances. The value and shortcomings of selective hemoglobin test before surgery require further evaluation. PMID- 1302790 TI - [Immune blood transfusion reactions and transfusion-induced immunosuppression]. PMID- 1302791 TI - [Hospital bulk oxygen and nitrous oxide delivery system: supply, design and danger]. PMID- 1302792 TI - Re-expansion pulmonary edema after removal of a huge intra-abdominal tumor. PMID- 1302793 TI - Anesthetic management in myasthenic parturient. PMID- 1302794 TI - [Misplacement of bilateral femoral venous catheters into the abdominal cavity]. PMID- 1302795 TI - Anesthetic consideration and postpartum care of severe preeclampsia-eclampsia complicated by acute pulmonary edema. PMID- 1302796 TI - [A case report of oculocardiac reflex-induced cardiac arrest]. PMID- 1302797 TI - Murine subcutaneous granulomatous zygomycosis induced by Absidia corymbifera. AB - Subcutaneous zygomycosis developed in 90% of mice killed from 1 to 9 weeks following subcutaneous inoculation of spores from Absidia corymbifera. Initially the inflammation was characterized as pyo-granulomatous, but after five to six weeks of infection the dominant cells were mononuclear, and giant cells and more regular conglomerates of granulomata were formed. Within the granulomata necroses also became more abundant with time. In animals developing mycosis fungal elements were restricted to the site of infection and were never observed in regional lymph nodes or internal organs examined by conventional and immunohistochemical staining methods. The localized extension of infection was accompanied by development of specific antibodies against somatic antigens from A. corymbifera as assessed by counterimmunoelectrophoresis. PMID- 1302798 TI - Relationship between digestive and killing abilities of neutrophils against Paracoccidioides brasiliensis. AB - Peripheral blood neutrophils (PMN) from patients with paracoccidioidomycosis killed and digested Paracoccidioides brasiliensis much less than did PMN from normal individuals or from patients with other diseases. However, deficiency in killing ability was less specific than digestive deficiency and correlated poorly with it. We conclude that the capacities of PMN to digest and kill P. brasiliensis are not intimately related phenomena, and that in paracoccidioidomycosis the key deficiency of neutrophil function is that of digestion of P. brasiliensis. PMID- 1302799 TI - Haematological alterations induced by biochemical fractions of Paracoccidioides brasiliensis in mice. AB - Biochemical fractions of Paracoccidioides brasiliensis were obtained for experimental inoculation in mice followed by haematological analysis. Dead total fungus, total fungus disrupted by ultrasonic waves, lipids of the fungus, supernatant of the lipid purification, and integral and disrupted fungus free of lipids were obtained. The six fractions were obtained from lyophilized yeasts of a recent isolate of P. brasiliensis and from a pool comprising equal amounts of four strains maintained in the laboratory for some time. Different doses of the 12 fractions were intraperitoneally inoculated into mice and haematological analysis was done 30 days later. No significant alterations were detected in the red blood cell series. However, the white blood cell series showed marked alterations, such as leukopenia, with relative neutrophilia and lymphopenia. Thrombocytosis occurred widely. The haematological alterations revealed associations with the injected doses without relation to the biochemical composition of the different fractions. No difference in the capacity for inducing haematological alterations was found between the fractions obtained from the recent isolate and from the older ones. PMID- 1302800 TI - Pathogenic fungi in human dwellings. AB - Airborne invasive fungal infections in various risk groups of people suffering from immunodeficiencies are an increasing problem for modern medicine. Because of the acute and rapid course of invasive infections, prevention is of principal significance. Such prevention mainly concerns the control of fungal spores in indoor air. In this connection the immediate environment offering ecological niches for growth and morphogenesis of infective particles of Aspergillus spp., Mucoraceae, Cryptococcus neoformans and some other yeast-like fungi is of main interest. The current problems of indoor air mycology, i.e. the epidemiology and ecology of pathogenic fungi in indoor air, can only be recognized and interpreted by centres routinely performing mycological diagnosis for all the various risk groups of patients. Models of specific surveillance of the most important fungal pathogens (e.g. Aspergillus spp. and Cryptococcus neoformans) in indoor air will be outlined and discussed. PMID- 1302801 TI - Hyperthermic treatment of sporotrichosis: experimental use of infrared and far infrared rays. AB - We used pocket warmers and infrared and far infrared rays to treat 14 cases of sporotrichosis, 7 in children and 7 in adults. There were 9 cases of the fixed cutaneous type and 5 of the lymphocutaneous type; 6 were located on the face and 8 on the limbs. Four cases were treated with pocket warmers, 5 with infrared rays, and 5 with far infrared rays. All lesions treated with pocket warmers were facial lesions in children; infrared and far infrared ray treatments were used in 3 children and 7 adults, 2 on facial lesions and 8 on lesions on the extremities. In treatments with infrared and far infrared rays, the amount of heat was greater than with the pocket warmers, and one 15-min treatment daily was sufficient to yield satisfactory results, but this method is difficult to use on children and on the face, and 40-min treatments two or three times a week proved unsatisfactory. Infrared and far infrared ray treatments allow the length of a single treatment to be reduced by three-quarters, in comparison with one pocket warmer treatment. PMID- 1302802 TI - Trichoderma viride infection in a liver transplant recipient. AB - A liver transplant recipient developed infection of a perihepatic haematoma due to Trichoderma viride. Before the infection was diagnosed, the patient received intense immuno-suppressive and prolonged antibacterial and anti-fungal therapies. Although the death of the patient was not directly related to the fungal infection, abundant quantities of this pathogen were recovered in the haematoma at post-mortem examination, despite previous surgical removal and treatment with amphotericin B and fluconazole. PMID- 1302803 TI - Rhodotorula fungaemia: a life-threatening complication of indwelling central venous catheters. AB - A 30-year-old woman receiving total parenteral nutrition via an indwelling central venous catheter for an intestinal motility disorder developed fever, tachycardia, tachypnea, and hypotension. Multiple blood cultures drawn through the catheter prior to these events, as well as a peripheral blood culture obtained earlier, grew the red yeast Rhodotorula rubra. The patient was critically ill for over one month but eventually recovered with therapy including the systemic antifungal agents amphotericin B and flucytosine and removal of the catheter. Although Rhodotorula has generally been regarded as having low pathogenicity, this case emphasizes the serious nature of Rhodotorula sepsis and suggests the need for both systemic antifungal therapy and removal of a colonized indwelling catheter. PMID- 1302804 TI - Fungaemia due to Candida pelliculosa in a case of acute pancreatitis. AB - We describe a case of fungaemia due to Candida pelliculosa (teleomorph: Hansenula anomala) in an otherwise non-immunocompromised patient with acute necrotizing pancreatitis of unknown origin. This species of Candida should be added to the list of pathogenic fungi which are increasingly important not only in patients with underlying immunosuppressive disease but also in patients with, for instance, severe surgical illness. PMID- 1302805 TI - Hepatosplenic infection caused by Candida parapsilosis in patients with acute leukemia. AB - Candida parapsilosis is an exceptional agent in hepatosplenic candidosis. Here we report two cases of hepatosplenic infection caused by Candida parapsilosis in two patients with acute leukaemia. Open liver-spleen biopsy and previously minimal exposure to systemic antifungal drugs led to a cultural diagnosis in both patients. This report confirms the importance of an early diagnosis of these diseases in order to undertake appropriate therapeutic regimens. PMID- 1302806 TI - Successful treatment of a Candida albicans sepsis with a combination of flucytosine and fluconazole. AB - A case of a severe Candida sepsis is reported, which was treated successfully by a combination therapy of flucytosine with fluconazole. After an extensive abdominal operation, a 70-year-old man developed a syndrome of fulminant sepsis due to Candida albicans with the beginnings of renal failure. The latter fact forced us to search for a therapeutic alternative to the classical amphotericin B plus flucytosine combination therapy. PMID- 1302807 TI - Shorter treatment for vaginal candidosis: comparison between single-dose oral fluconazole and three-day treatment with local miconazole. AB - Fluconazole is an effective, simple and safe, although slightly expensive, agent for the treatment of vaginal candidosis. Single-dose fluconazole (150 mg) administered orally in capsule form was compared with three-day local treatment with miconazole pessaries in the treatment of vaginal candidosis in a randomized study in Finland. Cure rates were good (> 80%) in randomized patient groups assessed both clinically and by the results of yeast cultures. Oral administration was preferred to local therapy by patients in both the miconazole and fluconazole groups. For the time being, fluconazole is not recommended for use during pregnancy or lactation. PMID- 1302808 TI - Synergistic interaction of miconazole and fluconazole at sub-MIC level on Candida albicans. AB - The in vitro combination effect of two azole antimycotics, miconazole and fluconazole, against Candida albicans was studied. When minimum (MIC) and sub minimum (sub-MIC) inhibitory concentration and fractional inhibitory concentration (FIC) determinations were made, a synergistic interaction of the two agents at the concentration well below their individual MICs (at sub-MIC levels) was evidenced. The FIC index values ranged from 0.3 to 1.0 and the synergy was characterized by the potentiation of fluconazole activity with miconazole. The synergistic effect was also confirmed by a turbidometric method. On the other hand, such a synergistic effect against Candida krusei was not confirmed. PMID- 1302809 TI - Low voltage scanning electron microscopy study of naftifine activity on Microsporum canis. AB - Scanning electron microscopy (SEM) is at present considered a good way to observe the morphological alterations induced by an antifungal on pathogenic fungi. Owing to its high precision, low voltage scanning electron microscopy (LVSEM) improves the quality of observations. The Microsporum canis morphology alterations induced by naftifine at a concentration of 0.9 microgram ml-1 (10 times the minimum inhibitory concentration (MIC) for 7 days were studied in LVSEM. The young lateral ramifications and the aborted buds take on a granulous aspect. These granulations can be localized as brassard shapes around hyphae. The mycelial filaments often appear irregularly swollen with bulbous tips. Macroconidia are selectively covered with a microfibrillar network. In addition, LVSEM on control samples reveals pavimentous angular structures on the macroconidial surface and fine granulations on the filament surface of M. canis unknown until now. A cytological study with transmission electron microscopy (TEM) of filaments altered by naftifine permitted us to observe the disorganization of cell wall fibrillar structure, an excessive plasma membrane undulation and an intracytoplasmic accumulation of large vesicles with probably lipidic contents. PMID- 1302810 TI - Preparation of antigens from Trichophyton mentagrophytes using a new semi-solid culture medium and their characterization by SDS-PAGE and immunological techniques. AB - A new semi-solid culture medium was developed by substituting the agar in Sabouraud glucose medium by Lutrol FC 127 (BASF, Ludwigshafen, Germany). This culture medium can be liquefied by cooling it down from the incubation temperature to 5-10 degrees C, thus allowing the full harvest of fungal mycelium without any contamination by the gelling agent for antigen preparation. More than 25 protein bands with molecular weights in the range of 98 to 12 kDa were fractionated by SDS-PAGE in antigen preparations from Trichophyton mentagrophytes. Hyperimmune antisera were raised in rabbits and used for immunological studies. Heat-inactivated mycelium was used for the absorption of antibodies against heat-stable cell wall constituents. This absorption facilitated the detection of specific protein bands during immunoblotting which revealed 17 protein antigen bands reacting with antibodies over a range of molecular weights from 98 to 24 kDa. PMID- 1302811 TI - Isoconazole nitrate versus clotrimazole in foot and nail infections due to Hendersonula toruloidea, Scytalidium hyalinum and dermatophytes. AB - A total of 40 coal miners, 35 with culturally proven mycotic infections of the feet and 5 with similarly proven infections of toenails due to Hendersonula toruloidea, Scytalidium hyalinum and dermatophytes, were treated with 1% cream of either isoconazole nitrate (Travogen) or clotrimazole (Canestan) for 4 weeks. The clinical cure rates for the isoconazole-treated group for itching, inflammation, scaling and maceration in the cases of foot infections were 89, 88, 83 and 83% respectively. For the clotrimazole-treated group, the cure rates were 76, 71, 82 and 80% respectively, for the similar symptoms. Toe web was the commonest site of infection and also most easily treated with either clotrimazole or isoconazole. The clinical and mycological cure rates 6 weeks after treatment were 80% for the isoconazole-treated group and 70% for the clotrimazole-treated group but the difference was not statistically significant (P > 0.01). None of the cases of toenail infection could be cured by treatment with either of the two drugs. PMID- 1302812 TI - Inhibition of growth of dermatophytes by Indian hair oils. AB - A survey on the use of hair oils for hair dressings by the Indian population revealed that mustard oil is preferred by males and coconut oil by females. Amla oil is used equally by both. These oils contain different percentages of various saturated and unsaturated fatty acids which largely determine their toxicity against dermatophytes. For Microsporum canis, M. gypseum and Trichophyton rubrum, amla oil was most toxic, followed by cantharidine and coconut oil, while Trichophyton mentagrophytes was most susceptible to coconut oil followed by amla and cantharidine oil. Mustard oil showed least toxicity to all four test species. The rarity of tinea capitis in India has been concluded to be due to the common use of hair oils by the Indian population. PMID- 1302813 TI - Dermatomycoses among industrial workers in Cross River State, Nigeria. AB - A survey of dermatomycoses was carried out amongst industrial workers in three different factories during the period 1987-1988. A total of 194 workers were screened, out of which 54 proved to be mycologically positive by microscopy and/or culture. Incidence was apparently highest amongst workers in a cement factory (Calcemco, 33.3%) followed by those in a wood factory (Seromwood, 30.8%) and a rubber factory (CREL, 26.2%). Pityriasis versicolor was the predominant clinical type of dermatomycosis, followed by tinea pedis. A total of 51 fungal organisms were identified. Malassezia furfur was the most prevalent causative agent (74.4%) followed by Trichophyton soudanense (5.8%), T. rubrum (3.9%) and Epidermophyton floccosum (3.9%). Other species identified were one isolate each of T. tonsurans, T. mentagrophytes, T. verrucosum, Candida tropicalis, Candida spec. and Geotrichum candidum. PMID- 1302814 TI - Dermatophytosis due to Trichophyton rubrum in northern Greece during the decade 1981-1990. AB - During the years 1981-1990 Trichophyton rubrum was the most frequent causative agent of dermatophytic infections in Northern Greece, especially in cases of tinea pedis, cruris, corporis, and unguium, as well as dermatophytosis of the hands. Between sexes there was a prevalence in women in tinea pedis and toenail infections. Men were particularly infected in the groin, the hands and the face. The chronic follicular dermatophytosis in the lower legs was also presented in women, but tinea corporis and fingernail infections showed no significant differences between the sexes. Also studied were the age of the patients, the inflammatory component of the lesions and the morphotypes of T. rubrum isolated. PMID- 1302815 TI - [Effect of histamine and serotonin on cerebral vascular resistance, volumetric and metabolic functions]. PMID- 1302816 TI - [Mechanism of self-maintenance of experimental atherogenic hyperlipoproteinemia]. AB - Disorders of lipid catabolism in the liver and increased formation and intensified secretion into the blood of lipoproteins synthesized in the liver evidently play a significant role in the maintenance of experimental atherogenic hyperlipoproteinemia induced in rabbits by prolonged administration of atherogenic lipoproteins. PMID- 1302817 TI - [Biological effect of laser radiation on the functional state of cardiomyocytes]. AB - Experiments were conducted on Wistar rats to study the effect of laser radiation (LR) with a wavelength of 632.8 and 890.0 nm and power of 0.0005-0.005 and 0.003 0.003 W/cm2, respectively, on the action potential (AP) and mechanical contraction of smooth muscle cells, as well as myocardial ATPase activity. LR with a wavelength of 632.8 and 890.0 nm in a dose of 3.0 J/cm2 activates Ca-ATP ase activity, increases the activity of the myocardial antioxidant system, reduces the Na-Ca current through the membrane, and accelerates the return of Ca2+ into the sarcoplasmic reticulum. LR with a wavelength of 632.8 nm reduces mainly the Ca flow, while LR with a wavelength of 890.0 nm reduces the Na current In a dose of more than 3.0 J/cm2 LR causes a damaging effect manifested by increased Ca2+ current in the slow channels, increase of amplitude, duration of AP and repolarization phase. Synergism of the action of LR with a wavelength of 632.8 and 890.0 nm and that of some antiarrhythmic agents (procainamide, lidocaine, ethmosin, ethacisin, verapamil) was encountered. PMID- 1302818 TI - [Laser irradiation of venous blood for prevention of reperfusion syndrome in myocardial infarction]. AB - The antioxidant effect encountered in laser irradiation of venous blood suggested the study of the possibility of its use for the prevention of the reperfusion syndrome in myocardial infarction (MI). Analysis of biochemical, electrophysiological, hemodynamic, and morphohistological data obtained in experiments on male rats and in clinical cases showed that irradiation of venous blood by the LG-75 helium-neon laser with a wavelength of 632.8 nm produced the best effect. The effect is realized through increase of collateral blood supply in the region of the MI and the antioxidant and antihypoxic action. PMID- 1302819 TI - [Effect of extremely high-frequency electromagnetic radiation on the function of skin sensory endings]. AB - The specific features of skin receptor function on the sole of the hind limb of an albino rat were studied in an acute experiment. Impulse activity recorded from the solitary fibres of the tibial nerve showed that receptor units (RU) responded to mechanical stimulation of the skin. Irradiation of the skin surface by low intensity millimeter band electromagnetic field (frequencies of 55.61 and 73 GHz) in the zone of the RU led to diminution of RU sensitivity to the mechanical stimulus. One half of the RU ceased to respond to the mechanical stimulation 25 minutes after irradiation. The other half continued responding to stimulation even after 35 minutes of irradiation, but the character of the RU response was significantly changed. A strict frequency-resonance dependence of the biological effects was revealed. It is concluded that electromagnetic radiation has a modulatory-inhibiting effect on the skin RU. The authors suggest a possible mechanism of realization of the effect of electromagnetic radiation of extremely high-frequencies and low power on the skin receptor function. PMID- 1302820 TI - [Relationship between alcoholic post-intoxication lesion of the heart in rats and the method of alcoholization]. PMID- 1302821 TI - [Effect of dibunol on lipid peroxidation and alpha-tocopherol level in the rat heart in acute hemorrhage]. AB - The authors studied the effect of a single injection of dibunol in a dose of 120 mg/kg on lipid peroxidation (LPO) and alpha-tocopherol (TP) level in the heart muscle in acute blood loss. The LPO products and alpha-tocopherol level were determined simultaneously in a heart homogenate 2 hours after the blood loss. It was established that the loss of blood leads to activation of LPO and reduction of the TP level in the myocardium. Dibunol injection inhibited LPO activation, reducing the content of LPO products to that in animals with a false operation (without blood loss), and increased the TP level also to that in a false operation. The decrease of the TP level in acute blood loss depends, evidently, on increased mobilization of TP from the myocardium due to the increased level of catecholamines (CA), while the increase of TP under the effect of dibunol occurs due to its inhibited mobilization from the myocardium, which is mediated by reduction of the CA level. PMID- 1302822 TI - [One of the possible means of restoring the circulating blood volume in shock]. AB - The possibility of increasing the efficacy of restoration of the circulating blood volume (CBV) in shock was demonstrated in experiments on 33 anesthesized female cats. Intramuscular injection of lactin one hour before blood loss (2% of body mass) in a dose of 5 U/kg or its intravenous infusion 90 minutes after blood loss in a dose of 50 U/kg was attended by restoration of the plasma volume in 5 hours. The prospects of further research into improvement of the efficacy of CBV in shock through activation of the body's reserves are substantiated. PMID- 1302823 TI - [Noradrenaline metabolism in the brain of young rats during formation of inherited stress-induced arterial hypertension]. AB - The noradrenaline (NA) metabolism rate was studied in discrete brain areas of young rats with inherited stress-induced arterial hypertension (ISIAH rats) in the period of rapid hypertension formation (4th week, 22nd-23rd days of life). The rate of metabolism was evaluated according to the NA concentration regression lines after inhibition of tyrosine hydroxylase oridopamine-beta-hydroxylase. The level of NA and the rate of its metabolism in the posterior hypothalamus, midbrain, and pons were higher in ISIAH rats than in normotensive Wistar rats. These parameters in the frontal cortex, anterior hypothalamus, and medulla oblongata were the same in the two rat strains. The possible role of NA metabolic changes in the development of inherited arterial hypertension is discussed. PMID- 1302824 TI - [Infusion therapy of experimental burn shock using the antihypoxant olifen]. PMID- 1302825 TI - [Relationship between metabolic changes in regional blood and tissues in ischemia of the extremities]. AB - The authors examined 56 patients with obliterating diseases (OD) of arteries of the lower extremities and conducted experiments on 97 male albino rats. In patients with OD the lactate content in the regional venous blood of the involved extremity increases proportionally to the severity of ischemia. No essential changes occur in the concentration of ATP and glucose. In rats with transitory ischemia of the extremities the lactate level in venous blood increases in the absence of changes of the ATP and glucose content; reduced concentration of ATP and glycogen was encountered in the ischemic muscles of the extremities. The mechanisms and significance of the disorders of metabolic parameters in ischemia are discussed. PMID- 1302826 TI - [Effect of protectors on morphofunctional changes in rat kidneys in tourniquet shock]. AB - The protective effect produced on the kidneys in tourniquet shock by thiol agents possessing antioxidant properties (unithiol, cystamine) was compared with that of a preparation of cell capsules of L. bulgaricus (CCLB). Tourniquet shock was modeled under ether Raush anesthesia by applying 8 turns of a rubber tourniquet to the hind limbs for 6 hours. Thirty minutes before removal of the tourniquet animals of the first group were given an injection of 1 ml of physiological solution, animals of the second group--20 mg/kg of unithol, those of the third group received an injection of 20 mg/kg of cystamine hydrochloride. Animals of the fourth group received 50 mg/kg of CCLB in 1 ml of physiological solution 7 days before the experiment. A marked protective effect of CCLB on the kidneys in tourniquet shock was established. According to the degree of the protective effect on the tissue of kidneys in tourniquet shock, the studied agents come in the following order: CCLB, cystamine, unithiol. PMID- 1302827 TI - [Features of glomerular filter permeability for specific serum proteins in various morphologic types of chronic glomerulonephritis]. PMID- 1302828 TI - [Effect of peptide immunomodulators on microlymphodynamics]. AB - Study of changes of some microlymphocirculatory parameters on the mesentery of anesthesized female albino rats in application of immunomodulators in 3-4 concentrations showed the following. Lympholin and gordox caused no changes of the studied parameters (tonic activity, rate and amplitude of rhythmic phase activity, rate of lymph flow). With gradual increase of concentration, Tactivin caused a greater constriction of the lymph vessels with a reduction of the amplitude of contractions. The changes of the rate of contractions was dose dependent with increase of the concentration the proportion of vessels with a diminished rate increased. Myelopid increased the rate of contractions with some increase in the rate of lymph flow. Dose-dependence was not found. Leukopeptide caused narrowing of the vessels with a dose-dependent increase of the lymph flow rate. Lienin only reduced the rate of the lymph flow. PMID- 1302829 TI - [Postradiation regeneration of hematopoiesis during pre-exposure of mice to systemic hyperthermia]. PMID- 1302830 TI - [Development of various forms of immunosuppression after exertion and heat exposure]. AB - In Wistar rats, 3-hour moderate exercise precipitated the development of antigen specific immunosuppression induced by large doses of sheep erythrocytes, while 5 hour exercise caused, in addition, the development of antigen-nonspecific immunosuppression. After 5-hour swimming splenic cells which did not adhere to the plastic secreted the antigen-specific factor (ASF), while cells adhering to the plastic secreted the antigen-nonspecific factor (ANSF). Immunosuppressive ASF had no effect on ANSF secretion, whereas the latter accelerated the secretion of ASF by the splenocytes of swimming rats. Administration of erythrocytes of swimming rats induced the secretion of immunosuppressive ANSF by splenic cells which adhered to the glass and this factor promoted ASF secretion in hyperimmunized rats. After warming, the erythrocytes lost their property of inducing ANSF secretion by cells which did not adhere to the glass, which led to secondary diminution of ASF secretion. PMID- 1302831 TI - [Frequency of acquired helplessness and initial probability of showing an elaborated reaction]. AB - The defense reflex of random performance of instrumental reaction (RPIR) had been produced in rats with different probabilities which were equal to 0.5; 0.25; 0.125 and 0.05 in respective experimental groups. Learning of animals was found to take place much faster when probabilities of RPIR were equal to 0.125 and 0.25 as compared with 0.5 and 0.05 values. One third rats which learned at 0.05 and 0.5 probabilities did not produce the reflex; the decrease in aroused, fall of body weight and other disturbances were observed and these findings may evident development of acquired helplessness about. It is supposed that optimal circumstances are occurred at different probabilities of RPIR conditions. PMID- 1302832 TI - [Pathogenesis of fever after operations on the gastrointestinal tract]. AB - It was established on dog experiments and in operations on patients that the severity and duration of a febrile response after operations on the intestine are determined by the degree of contamination of the abdominal cavity through a physically air-tight intestinal suture. PMID- 1302833 TI - [Effect of stress on steroidogenesis in pregnancy (experimental study on primates]. PMID- 1302834 TI - [A new method of obtaining brain biopsy specimens for studies of energy-rich phosphate metabolism]. PMID- 1302835 TI - [Importance of determining halo-formation in comprehensive diagnosis of neoplasms in the large salivary glands]. AB - An original diagnostic test in study of the functional state of segmented neutrophils, based on the halo-formation phenomenon, was investigated in patients with neoplastic and non-neoplastic diseases of the large salivary glands. Donors formed the control group. Analysis of the results showed a marked increase of the number of halo forming cells in patients with various forms of malignant new growths of these organs. The suggested test is recommended for use as an index of the functional activity of segmented neutrophils in malignant growth. PMID- 1302836 TI - [Development of S. V. Anichkov's ideas in basic research on neurogenic visceral pathology and its drug therapy (100th anniversary of the birth of S. V. Anichkov, Academician of the Russian Academy of Medical Sciences)]. PMID- 1302837 TI - [Nociceptive sensitivity of rabbits in varying localization of pain stimuli and naloxone administration]. AB - Study of the dynamics of changes of evoked potential (EP) amplitude in electrodental and electrocutaneous stimulation (EDS and ECS, respectively) as an index of the perceptual component of the nociceptive reaction showed that 0.2 mg/kg and 0.5 mg/kg doses of naloxone produce both a hyper- and an analgesic effect in rabbits. The effect of naloxone depended on the individual properties of the rabbits, while its degree was determined by the localization of the nociceptive stimulus. The animals' individual properties were manifested by the presence or absence of an analgesic effect of auricular electrostimulation- acupuncture-sensitive (AS) or acupuncture-resistant (AR) rabbits. Naloxone injection caused a dose-dependent hyperalgesic effect in AS animals and an analgesic effect in AR rabbits in EDS. Similar effects were recorded in ECS, but their degree differed: hyperalgesia in AS rabbits was demonstrated more clearly than analgesia in AR animals. PMID- 1302838 TI - [Microcirculation in the dynamics of developing deafferentation pain syndrome]. PMID- 1302839 TI - [Heterogeneity of immunoreactive prolactin in hyperprolactinemia of various origin]. AB - Study of molecular heterogeneity of immunoreactive prolactin in patients with macro- and microprolactinomas and idiopathic hyperprolactinemia has shown heterogeneity of the total blood immunoreactive prolactin pool in all the examined patients. This pool included three basic forms with molecular masses about 23, 50, and over 100 kD (23K-, 50K-, 100K-prolactin), whose ratios essentially differed in individual patients. Physiologically the most active monomeric 23K form of prolactin predominated in the blood of patients with hyperprolactinemia due to hypophyseal micro- and macroadenomas, parallelled by manifest signs of galactorrhea and hypogonadism; the content of this form may reach 95% of the total immunoreactive hormone. Patients with hyperprolactinemia of obscure origin present with quite the contrary ratio of prolactin immunoreactive forms with the predominance of high-molecular 100K form of the hormone, whose share may reach 80-90%. Such cases of hyperprolactinemia may be associated with the absence of clear-cut clinical manifestations, including such as galactorrhea and menstrual cycle disorders, and with inefficacy of traditional therapy. Such cases were tentatively classified as 'the high-molecular prolactin syndrome' and need further research. PMID- 1302840 TI - [Bone tissue in patients with hyperprolactinemic hypogonadism]. AB - Sixteen women with hyperprolactinemia were examined for Ca metabolism, osseous metabolism, mineral saturation of bone tissue in the thoracic portion of the spine and radius. Lowered mineral saturation of the thoracic vertebrae was detected in 69% of the examinees, that of the distal segment of the radius in 44%. Reduction of the mineral saturation of the spine was in negative correlation with the blood prolactin level and length of amenorrhea. No changes in the bone resorption biochemistry or Ca metabolism were detected. A marked reduction of blood osteocalcin level that reflects osteoblast function was detected, its blood concentration being in negative correlation with prolactin level. No relationships between mineral saturation of bone tissue, prolactin, and osteocalcin, on the one hand, and blood estradiol level, on the other, were observed. These data suggest that osteopathy in hyperprolactinemic hypogonadism is due to reduced bone formation and not to reduced estradiol production. PMID- 1302841 TI - [UV-irradiation of the blood in the treatment of polycystic ovary syndrome]. AB - Effect of extracorporeal UV irradiation of the blood on the clinical picture and hormonal profile of patients with the polycystic ovaries syndrome was under study. 119 women were administered 582 sessions, and in 54 of these the results were followed up for 1-25 months. A good clinical effect was achieved in 88.9% of these cases, it consisted in recovery of the cycle rhythm (70.7%), pregnancy (29.2%), reduction of hirsutism manifestations (19.04%), decrease of galactorrhea (41.7%), cessation or alleviation of headaches (86.2%), body mass reduction (40%), arterial pressure normalization (43.8%). Well-being of the majority of women was improved by therapy. 17-ketosteroids excretion normalized and persisted normal in a month after the treatment. Blood LH level and the LH/FSH ratio significantly reduced in those in whom these values were elevated in disease. Elimination of hyperandrogenism and a trend to normalization of gonadotropin secretion, resulting from extracorporeal UV irradiation of the blood, indicate that such treatment modality is pathogenetically grounded and justify its use in the treatment of women with the polycystic ovaries syndrome. PMID- 1302842 TI - [Difficulties in the diagnosis and treatment of infertility caused by the combination of microprolactinoma and polycystic ovaries]. PMID- 1302843 TI - [Comparison of the data of palpation and ultrasonic examination in assessing the dimensions of the thyroid gland]. AB - Comparison of the thyroid-sizes estimated by palpation and ultrasonic scanning in 282 women and 178 men has shown that if the thyroid is small (from 0 to 2nd degree, according to O. V. Nikolayev's classification), its size cannot be estimated by palpation and this method fails to assess the endemic goiter in epidemiologic surveys. Correlation between the thyroid size estimated by palpation and its ultrasonically assessed volume has made up 0.346 (p < 0.001) in women and 0.193 (p < 0.01) in men. Ultrasonic assessment of the thyroid volume appears useful both for clinical and epidemiologic studies. PMID- 1302844 TI - [Surgical tactics for treatment of thyroid gland diseases from an oncologic standpoint]. AB - Analyzing the 30-year experience of a hospital, the authors come to a conclusion that the incidence of thyroid carcinoma among 10034 patients operated on has grown by 2.1 times. The number of thyroid cases grew mostly at the expense of a higher incidence of carcinomas of goiter-changed thyroid. The risk of appearance of malignant growth foci is virtually the same in different thyroid diseases and makes up 3%, as evidenced by the data of studies of the macro- and micro preparations of the thyroid of 2930 patients with various thyroid conditions. This fact is explained by the effects of the same etiopathogenic factors studied in 595 patients with nodular tumors of the thyroid, though the incidence of these factors varies and is related to the nosologic entity. Prolonged follow-up and conservative therapy of thyroid patients are unjustified. PMID- 1302845 TI - [Prevalence of endemic goiter in Byelarus]. PMID- 1302846 TI - [Lipid peroxidation and antioxidant enzymatic defense in patients with newly detected insulin-dependent diabetes mellitus]. AB - Studies of lipid peroxidation and antioxidant enzymic defense in red cell membranes in 23 patients with newly detected insulin-dependent diabetes mellitus have revealed a statistically significant (2-fold) elevation of malonic dialdehyde lipid peroxidation products and a trend to a rise in the levels of lipid peroxides. This is parallelled by a certain overstrain of the cellular antioxidant defense system. The authors discuss the usefulness of administering antioxidant therapy at the onset of the disease in order to prevent the toxic injury of beta-cells and vascular endothelium cells by lipid peroxidation products. PMID- 1302847 TI - [Use of the lipolytic drug mevacor in the treatment of patients with diabetes mellitus]. AB - Stable compensation of diabetes mellitus, including normolipidemia, underlies the therapy of diabetic angiopathies. Mevacor represents a nonactive lactone form of a certain hydroxy acid, a potent inhibitor of endogenous synthesis of cholesterol, conducive to blood cholesterol reduction. The aim of the present study was the assessment of the efficacy of this drug in therapy of patients with diabetes mellitus. Ten patients were administered mevacor in a dose of 20 mg for a month. Such therapy was conducive to a significant reduction of the levels of cholesterol, LNP cholesterol, triglycerides, and cholesterol/LVP ratio. It also promoted a reduction of the content of lipid peroxidation products in the blood, these products being an active factor of vessel destruction. The levels of hydroperoxides, blood serum and red cell malonic dialdehyde, and superoxide dismutase were also reduced. These results necessitate addition of mevacor to a complex of therapy for diabetes to normalize lipid metabolism. PMID- 1302848 TI - [Formulas for estimating the RD parameter in the algorithm of statistical regulation of glycemia with a biostator]. AB - An analytical approach to the estimation of the RD parameter for this algorithm has been developed; up to the latest time this parameter was chosen by the investigators by the 'try and miss' technique, based on the scientist's intuition. Three interactive formulae for the calculation of the RD parameter were derived, differing by the degree of the parameter modulation in the iterative procedure of the search for the precise value. The method for estimation of glucose utilization rate was adapted for the clamp method results obtained with a biostator; this method was for the first time used in the semiautomated glycemia regulation, that may improve the accuracy of glucose tolerance estimation. PMID- 1302849 TI - [Hyperandrogenism syndrome: differential diagnostic approaches and diagnostic criteria (lecture)]. PMID- 1302850 TI - [Disorder of neuroendocrine regulation of sexual behavior of male rats with streptozotocin-induced diabetes]. AB - The present paper presents studies of the sexual behavior characteristics and the associated changes of LH releasing factor and of sex hormone receptor concentrations in hypothalamic regions involved in the regulation of sexual behavior activity and hypophyseal gonadotropic function (the anterior preoptic and mediobasal regions) of rats with streptozotocin-induced diabetes. The activities of both motivational and copulative components of sex behavior of such rats were found reduced. These changes were parallelled by LH-RH reduction in the median eminence and in the synaptosomal fraction of the anterior preoptic and mediobasal regions. An increased concentration of estradiol nuclear receptors was found in the anterior preoptic region, that may be responsible for the male feminization in diabetes and for weaker male sexual activity parameters. Blood levels of LH and FSH in experimental rats were virtually the same as in the reference animals, whereas prolactin and testosterone levels were reduced in the presence of elevated estradiol content. The majority of the detected hormonal shifts and sexual behavior characteristics normalized after compensatory insulin therapy. The authors come to a conclusion on the neuroendocrine disorders at the level of the CNS in animals with experimental diabetes during the formation of the motivational and copulative components of sexual behavior. PMID- 1302851 TI - [Role of cytoplasmic proteins in the process of thyroxine stimulation of protein phosphorylation in rat liver and brain]. AB - The role of thyroxin and thyroxin action modulator (cytoplasmic protein mediating some hormonal effects on the mitochondria and nucleus) in rat liver and brain protein phosphorylation was studied in experiments. In the liver, an organ sensitive to thyroid hormones, the modulator was found to stimulate the activity of specific protein kinases contributing to protein phosphorylation, and co incubation of physiologic concentrations of T4 with the modulator enhanced the stimulatory effect. In the brain change of the thyroid status did not change the protein kinase activation. Incubation of T4 and thyroxin effect modulator did not change the enzymic activity either. PMID- 1302853 TI - [Free radical processes in the pathogenesis of alloxan diabetes]. AB - Presents the results of studies of carbohydrate and peroxide metabolism, of antioxidant content in rats with alloxan diabetes under various levels of alimentary antioxidant consumption. Alloxan administration was found to result in biochemical and morphologic shifts characteristic of diabetes mellitus. The development of these changes runs against the background of enhanced free-radical processes. Simulation of alloxan diabetes in deficiency of alimentary antioxidants is conducive to the development of alloxan diabetes. The authors discuss the contribution of free-radical processes to the pathogenesis of alloxan diabetes and come to a conclusion on the usefulness of including antioxidant drugs in to a complex of therapeutic measures in this condition. PMID- 1302852 TI - [Effect of protein content in rat diet on water-soluble vitamin metabolism in streptozotocin-induced diabetes]. AB - Water-soluble group B vitamins metabolism was studied over the course of streptozotocin-induced diabetes mellitus in rats fed semisynthetic isocaloric diets containing 18 and 50% of protein. A high-protein diet in diabetes mellitus does not influence riboflavin metabolism disordered in this disease but reduced 4 pyridoxyl acid excretion to the level characteristic of healthy animals. The observed trend to an increase of liver nicotinamide coenzymes levels and of 1 methylnicotinamide urinary excretion reflects increased niacin synthesis from the diet protein tryptophan, for niacin level is reduced in diabetes. PMID- 1302854 TI - [The human complement system and diabetes mellitus]. PMID- 1302855 TI - [Status of and prospects for neuroendocrine research on reproductive system physiology]. PMID- 1302857 TI - [Basic terms in psychotherapy in patients with schizophrenia]. PMID- 1302856 TI - [Minimum necessity of the skill and knowledge in basic psychiatry]. PMID- 1302858 TI - [Analysis of work matters in psychiatric departments in general hospitals- special reference to length of patient-interview time]. PMID- 1302859 TI - [Basic problems in patient care team approach to psychiatric-inpatient therapy]. PMID- 1302860 TI - [Informed consent and psychotherapy]. PMID- 1302861 TI - Lidocaine deaths: nurse convicted of murders. PMID- 1302862 TI - Is R.N. practice of medicine negligence per se? Case in point: Turek v. Elizabeth Com. Health Ctr (488 N.W. 2d 567--NE [1992]). PMID- 1302863 TI - Legal case briefs for nurses. OR: sexually explicit photographs of corpses: licence revocation upheld. PA: automatic doors close on patient: nurse liability issue. PMID- 1302864 TI - Fetal distress: "Failure to call for help". Case in point: Fairfax Hosp. System, Inc. v. McCarty (419 S.E.2d 621--VA [1992]). PMID- 1302865 TI - [Evaluation of antimicrobial drugs and atmospheres for the isolation of Campylobacter fetus subspp. from the bovine genital tract]. AB - Growth of 3 reference bovine C. fetus strains in media with and without antibiotics and bacteriostats active against the most common contaminant bacteria in the bovine genital tract was evaluated. In addition, 2 regional bovine C. fetus strains and 1 reference C. sputorum biovar bubulus strain were used in some experiments. Reference strain C. fetus subsp. venerealis was completely inhibited by polymyxin (> or = 0.25 IU/ml) whereas the other C. fetus strains were not inhibited. In Shepler's medium supplemented with rifampicin (10 micrograms/ml) subsp. fetus, was the only one to grow. When rifampicin was used at 5 micrograms/ml together with a reduced dose of the other Shepler's antibiotics, especially polymyxin B (0.85 IU/ml), subsp. venerealis was able to grow; nevertheless even at such a reduced dose, rifampicin was inhibitory for the biotype intermedius. It was demonstrated that triclosan (Irgasan) could be very useful at < or = 10 micrograms/ml in media with added blood, < or = 6 micrograms/ml in brucella broth and < or = 3 micrograms/ml in Mueller-Hinton broth for isolation of all subspecies of C. fetus. The sensitivity of C. fetus to 5-fluorouracil was variable: subsp. fetus was resistant (up to 800 micrograms/ml) whereas subspp. venerealis and biotype intermedius grew slowly or sometimes did not grow at all in concentrations of 6.25 micrograms/ml onwards. Fosfomycin was inhibitory to all C. fetus strains at > or = 50 micrograms/ml. C. sputorum biovar. bubulus was less inhibited than C. fetus with triclosan grew up to more than 100 micrograms/ml, with 5-fluorouracil up to 100 micrograms/ml and with fosfomycin up to 50 micrograms/ml. Growth of C. fetus subspp. was compared in different microaerophilic atmospheres contained in anaerobic jars (Oxoid HP 11) without palladium catalyzer. Growth with nitrogen or hydrogen was similar. When jars were replaced by 15 x 13 cm cylindrical cans without valves or gas measurement devices only pure hydrogen supported satisfactory growth of all C. fetus subspp. and C. sputorum biovar. bubulus strains. The candle system, a commercial nitrogen rich gas mixture and pure carbonic anhydride prepared in these cans failed to enable these strains to grow. C. fetus subsp. fetus was more aero-tolerant than subsp. venerealis and its biotype intermedius and was able to grow, although very weakly, with only carbonic anhydride added to an aerobic atmosphere. The growth obtained using a commercial gas generating microaerophilic kit (Oxoid BR-56) was comparable to the one achieved with the hydrogen rich atmosphere prepared in our laboratory. PMID- 1302866 TI - [Effect of glucose and lactose on the utilization of citrate by Lactobacillus casei subsp. rhamnosus ATCC 7469]. AB - The utilization of citrate by Lactobacillus casei subsp. rhamnosus ATCC 7469 in a complex medium containing glucose, lactose or citrate was investigated, as an approach to the question of the transport of this acid and the possible relationship with the production of flavour compounds (diacetyl and acetoin). This lactobacillus uses citrate as an energy source in the absence of carbohydrates. External pH and growth increases when citrate is added to complex medium. The presence of citrate does not affect glucose uptake. L. casei ATCC 7469 possibly uses a transport system for citrate utilization, and citrate uptake seems to be under glucose or lactose control. Lactose only inhibits the entrance of citrate at high concentration while the utilization of this acid was negatively regulated by low glucose concentration. PMID- 1302867 TI - [Prevalence in Tucuman of Chlamydia trachomatis and Ureaplasma urealyticum in sexually active women]. AB - A group of 298 sexually active women who consulted for cervicitis, sterility or infertility were studied to detect the prevalence of Chlamydia trachomatis and Ureaplasma urealyticum and also to correlate the presence of these pathogens with tube damage. Chlamydial antigens were detected with a fluorescent commercial reagent with specific monoclonal antibodies. The isolation of U. urealyticum was made following the Shepard and Lunceford (19) techniques. In all samples of endocervical canal, we observed a higher incidence of chlamydial antigens (42.8%) with respect to U. urealyticum (5.7%). In peritoneal liquid the values were 38.8% and 5.5%, respectively. In the group of infertile women, we observed a higher incidence of C. trachomatis (49.5%), with 31.7% in the sterile group and 53.2% in those women with cervicitis without failures in reproduction. The frequency of U. urealyticum was 11.1%, 6.1% and 4%, respectively. According to the results obtained we can postulate that there is no correlation between infections produced by C. trachomatis and U. urealyticum and failures in reproduction. PMID- 1302868 TI - [Numerical taxonomy of the genus Desulfovibrio by group analysis]. AB - The Desulfovibrio genus has a particular interest because it includes the microorganisms connected with the corrosion produced microbiologically. The taxonomy of the genus shows disadvantages due to its metabolical and physiological characteristics. In this paper, 14 strains of the Desulfovibrio type were studied from the metabolical point of view. Numeric taxonomy was carried out according to the Group Analysis method, using and comparing the change possibilities of the method. The Consensus Method was also applied. The results obtained indicate a low metabolic activity of the strains with regard to the number of compounds which can be used as energy source. The taxonomic method showed a better structure with more clear divisions, corresponding to Simple Matching coefficient (which coincides with other symmetric coefficients and with the distance coefficient) with average bond (UPGMA). It is estimated that the present classification will vary in time with new strains with different metabolic characteristics. The two groups of bacteria correspond to those with more and less degrading ability. PMID- 1302869 TI - [Analysis of principal coordinates and factorial correspondence analysis applied to the taxonomy of type strains of Desulfovibrio]. AB - Bacterial taxonomy using mathematical methods can be carried out with different techniques. Two techniques are used in this paper: analysis of principal coordinates and factor analysis of correspondences. The first one allows 2 and 3 dimension graphs of bacteria, thus showing their relationship considering proximity. The second one gives new data because it is an analysis which allows to connect bacteria to the reactions which identify them. In order to carry out these analyses 14 strains of the Desulfovibrio genus were studied, thus obtaining a classification consistent with other numeric method (group analysis with Simple Matching coefficient of average bond) to which it adds new information. PMID- 1302870 TI - Brain secretory peptides of the silkmoth Bombyx mori: prothoracicotropic hormone and bombyxin. PMID- 1302871 TI - Alternative mRNA splicing in the nervous system. PMID- 1302872 TI - Regulation of vasopressin and oxytocin gene expression by estrogen and thyroid hormone. PMID- 1302873 TI - Mutant vasopressin precursor producing cells of the homozygous Brattleboro rat as a model for co-expression of neuropeptides. AB - The homozygous Brattleboro rat (di/di) synthesizes a VP precursor with an abnormal C terminus, which is not transported from the rough endoplasmic reticulum to the Golgi apparatus. In addition, the phenotypic expression of co existing peptides is differentially disturbed. Ang II and 7B2 are two of the peptides which are not detectable, whereas other peptides (e.g. galanin) are clearly expressed in mutant VP cells. During postnatal life a small but increasing number of solitary post-mitotic VP neurons of the di/di rat undergoes a switch to a heterozygous phenotype. At the same time Ang II and 7B2 show up again in these heterozygous cells, which suggests that for the expression of 7B2, but not for that of other peptides (e.g. galanin), a normal VP precursor is required. A possible underlying mechanism (i.e. the existence of several domains on the endoplasmic reticulum involved in the translocation of sets of neuropeptides) for this differential phenotypic expression of co-existing peptides is discussed. PMID- 1302874 TI - Structure and evolution of insulin and insulin-like growth factors in chordates. PMID- 1302875 TI - Purification of a new neuropeptide from locust corpus cardiacum which influences ileal transport. PMID- 1302876 TI - Molecular genetic analysis of the FMRFamide-related neuropeptides in Drosophila. PMID- 1302877 TI - Topographical displacement of neuropeptide-producing nuclei as an indicator of evolutionary brain development. PMID- 1302878 TI - The biosynthesis and processing of neuroendocrine peptides: identification of proprotein convertases involved in intravesicular processing. PMID- 1302879 TI - Relationships among the FMRFamide-like peptides. AB - The nuclear family of FaRPs (comprising those peptides that are, on compelling evidence, homologous) appears to be restricted to the protostome invertebrate phyla: i.e. Mollusca, Arthropoda, Annelida and Nematoda. Neither the origin nor the range of the family has been definitively established. That is, no genuine homologs have been demonstrated yet in the flatworms (though not for lack of trying), and neither the pseudocoelomate phyla related to the nematodes, nor the coelomate relatives of the annelids have been examined. The extended family of FaRPs (including peptides with little consistent sequence similarity beyond a penultimate Arg and an amidated hydrophobic residue at the C-terminal) exists in all phyla. Such a superfamily was probably first proposed by Morris et al. (1982), whose sequencing of SCPB suggested to them a class of peptides, "... the key unit for biological activity being Phe-A-Arg-B-amide (where A and B are also hydrophobic amino acids)." The ubiquity of the convergent FaRPs could reflect a conserved family of complementary heptahelical receptors requiring the arginyl residue for binding (Price and Greenberg, 1989). But another selective advantage would be the protection provided by a penultimate Arg against certain deamidating peptidases, found so far in yeast and mammals (Jackman et al., 1990). PMID- 1302880 TI - Routing and release of input and output messengers of peptidergic systems. PMID- 1302881 TI - Cellular oscillators and biological timing: the role of proteins and Ca2+. PMID- 1302882 TI - Cholecystokinin in the control of ingestive behavior. PMID- 1302883 TI - Egg laying in the hermaphrodite pond snail Lymnaea stagnalis. PMID- 1302884 TI - The eclosion hormone system of insects. PMID- 1302885 TI - The anti-gonadotropic neuropeptide schistosomin interferes with peripheral and central neuroendocrine mechanisms involved in the regulation of reproduction and growth in the schistosome-infected snail Lymnaea stagnalis. PMID- 1302886 TI - Molecular evolution of neurohypophysial hormone precursors. PMID- 1302887 TI - A vasopressin-related peptide in the mollusc Lymnaea stagnalis: peptide structure, prohormone organization, evolutionary and functional aspects of Lymnaea conopressin. PMID- 1302888 TI - Models for the study of cell-specific neuropeptide gene expression. PMID- 1302889 TI - Neuropeptide gene expression in transgenic animals. AB - Transgenic animal techniques offer today's neuroscientist the ability to experimentally manipulate neurosecretory systems with a precision undreamt of by our predecessors. The range of techniques now available, building as it does on our growing knowledge of physiological systems at the inter- and intercellular level, allows us to critically define molecular lesions and ask about their consequences to the whole organism. Neuroscientist should grasp the opportunities afforded by these recent developments. PMID- 1302890 TI - Spatiotemporal patterns of transcription factor gene expression accompanying the development and plasticity of cell phenotypes in the neuroendocrine system. PMID- 1302891 TI - Residence time distribution of diazepam in the isolated perfused rat liver. Analysis with the axial dispersion model. AB - The application of the axial dispersion model to diazepam hepatic elimination was evaluated using data obtained for impulse-response experiments with diazepam in the single-pass isolated perfused rat liver preparation. The transient form of the two-compartment dispersion model was applied to the output concentration versus time profile of diazepam after bolus input of a radiolabelled tracer into the hepatic portal vein (n = 4), providing DN and CLint estimates of 0.251 +/- 0.093 and 135 +/- 59 ml min-1, respectively. In contrast, the one-compartment form of the axial dispersion model, which assumes instantaneous transversal distribution of substance to the accessible spaces within the liver, could not adequately describe the residence time distribution (RTD) of diazepam. Furthermore, the magnitude of DN, a stochastic parameter which characterizes the axial spreading of solutes during transit through the liver, is similar to that determined for non-eliminated substances such as erythrocytes, albumin, sucrose and water. These findings suggest that the dispersion of diazepam in the perfused rat liver is determined primarily by the architecture of the hepatic microvasculature. PMID- 1302892 TI - Potential induction of osteogenesis by systemic administration of bovine bone proteins. AB - This study shows, apparently for the first time, that the administration of bone derived proteins (putative bone growth factors) obtained from bovine demineralized maxillaries has a direct effect on osteogenesis, affecting significantly some markers of bone formation such as lactate dehydrogenase activity and serum osteocalcin. Also, collagen deposition and bone protein turnover were markedly increased by the treatment, which may have important biological and clinical applications. PMID- 1302893 TI - Analysis by digital simulation of the peripheral and renal resistance in hypovolemic hypotension. AB - A haemorrhage was simulated and analysis of dynamic behaviour of renal resistance, renal nervous activity and peripheral resistances were processed, with the aim of studying the paradoxical behaviour of renal resistance as opposed to peripheral resistances and the increase of sympathetic activity in hypovolemic shock situations using both non-linear models of the renal blood flow and arterial pressure and body fluids. The following conclusions can be made after comparing the results obtained by simulation with data related to animal experimentation models: the model is useful for its use in the analysis of nervous activity, resistance and renal flow in hypovolemic shock situations in humans and the control structure it puts forward can explain the paradoxical behaviour of renal vascular resistance as opposed to the peripheral resistances and the increase in the renal nervous activity in the aforementioned circumstances. PMID- 1302894 TI - Biological characterization of a formulated allergoid from Dermatophagoides pteronyssinus. AB - A comparative study between the biological properties of the allergen Dermatophagoides pteronyssinus (Dp) and its formulated allergoid (DpHCHO) was performed. After immunizing rats with Dp or DpHCHO the serum level time course of IgE and IgG was determined by passive cutaneous anaphylaxis (PCA) and indirect ELISA, respectively. The avidity for IgE (PCA and PCA-inhibition) or IgG (indirect ELISA and ELISA inhibition) and the ability to induce anaphylactic shock were also determined. Serum IgE pattern differs between Dp and DpHCHO while IgG levels were greater after DpHCHO. The allergoid has lost the ability to bind IgE while its avidity for IgG falls 5-6 times. The allergoid, but not the allergen, fails to induce anaphylactic shock. A schedule for assaying the biological characteristics of allergoids is presented. PMID- 1302895 TI - Unilateral ovariectomy, flutamide treatment and HCG reverse the anovulatory action of antiprogesterone RU486 in rat. AB - Administration of antiprogesterone RU486 (4 mg/day) from estrus through proestrus to cyclic rats blocked ovulation. Moreover, RU486 increased basal serum concentrations of LH, PRL, testosterone and estradiol, while it decreased basal serum concentration of FSH. Both unilateral ovariectomy and antiandrogen flutamide treatment, as well as an ovulatory injection of HCG in the proestrus afternoon partially reversed, the ovulatory blockade of RU486. These results indicate that both the decreased FSH concentration and the increased testosterone concentration, as well as the reduced ovulatory LH release are responsible for the anovulatory effects of RU486. PMID- 1302896 TI - [Regional distribution of brain aminopeptidases in the rat]. AB - Soluble and membrane-bound aminopeptidase activities in eleven regions of the rat brain were assayed using L-leucine-2-naphthylamide as a substrate. In addition, two metabolic enzymatic activities were compared: lactate dehydrogenase and aspartate aminotransferase. All enzymatic activities showed significant regional differences when the data were analyzed statistically. Soluble aminopeptidase and aspartate aminotransferase activities were significantly lower in cortical than in subcortical areas. Membrane-bound aminopeptidase activity levels were higher in cortical areas. Lactate dehydrogenase activities did no differ between cortical areas and the rest of the zones studied. However, while no wide regional differences were found for the other enzymatic activities, membrane-bound aminopeptidase varied markedly across brain regions: a 5-fold difference was observed between zones. The differential distribution of this enzymatic activity is consistent with the hypothesis that it is responsible for the enzymatic inactivation of some neuroactive peptides. PMID- 1302897 TI - Comparative determinations of low-density-lipoprotein-cholesterol. AB - Two different methods for low-density-lipoprotein-cholesterol (LDL-C) determination were comparatively used. The heparin-sodium citrate (pH 5.12) precipitation method gave similar LDL-C results to the ones given by the Friedewald et al. formula (3.2 vs 3.3 mmol/l) in 187 men. Values obtained using both methods show a very high and significant correlation (r > 0.9; p < 0.001). However, LDL-C values obtained with the precipitation method were 15% higher in hypertriglyceridemics (triglycerides (Tg) > or = 2.3 mmol/l). A paired-comparison between data obtained by both methods indicates a clear serum Tg-values influence, because LDL-C values obtained by the precipitation method were significantly more frequently higher (p < 0.05 or p < 0.01) than LDL-C values obtained using the Friedewald's formula in hypertriglyceridemic men (Tg > or = 1.7 mmol/l or Tg > or = 2.3 mmol/l respectively). When a 3.9 mmol/l LDL-C level break was chosen, Friedewald's formula gave 13% false hypercholesterolemics. The influence of Tg was again significant in men with both, hypercholesterolemia and hypertriglyceridemia, while LDL-C values obtained by the precipitation method were significantly more frequently higher (p < 0.01). PMID- 1302898 TI - Effect of maternal food restriction on the evolution of pregnancy in the rat. AB - The present work analyzes the role of food and water intake, nitrogen balance, and in vivo D-glucose intestinal absorption in body weight gain during the second half of pregnancy in malnourished mother rats. Our results indicate that nitrogen balance and intestinal absorption of D-glucose were not changed as a result of food restriction, but important negative correlations between water intake and micturition and weight gain and micturition were found in experimental mothers. The retention of water seems to be one of the most important factor influencing body weight gain in malnourished mother rats in the second half of pregnancy. PMID- 1302899 TI - Effects of hyperprolactinemia on prolactin and LH pulsatile pattern in female rats. AB - Prolactin (PRL) and luteinizing hormone (LH) secretions are very closely-related. To further understand these mechanisms, the pulsatile secretion pattern of both hormones in experimentally-induced hyperprolactinemia has been studied in adult female rats. Hyperprolactinemia was induced by the transplanting of two pituitary glands. Nine days after the transplant operation, rats were bled (75 or 100 microliters/7 min for 3 h). Serum samples were analyzed for prolactin and LH values by RIA. Hyperprolactinemia modifies pulsatile PRL secretion by increasing the absolute amplitude and duration of the peaks together with a decrease in their frequency. Also, the mean values of the hormone during the whole studied period were increased. Hyperprolactinemia was followed by an increase in the mean values of LH and in the absolute amplitude of the peaks. All these results suggest that hyperprolactinemia induced by pituitary grafting in adult female rats, is followed by a significant change in prolactin and LH pulsatility, which may explain, to some extent, the effects of hyperprolactinemia on reproduction. PMID- 1302900 TI - [New types of jobs. First negotiate, then appoint]. PMID- 1302901 TI - [AIDS--old routines are hard to eradicate]. PMID- 1302902 TI - [AIDS--small risks with enormous consequences]. PMID- 1302903 TI - [Quality control--a strategic tool]. PMID- 1302904 TI - [Research. The first Master in Nursing]. PMID- 1302905 TI - [Research. Need for reconciliation. Interview by Lars Peter Bergqvist]. PMID- 1302906 TI - [Nursing story. I am paying for my stay here]. PMID- 1302907 TI - [PKA (Pension Fund Administration). Pension Fund perceives crisis]. PMID- 1302908 TI - [The antitoxic action of xenogeneic spleen in treating the suppurative-septic complications in surgery]. AB - The article presents results of using hemoperfusion through the swine spleen and infusions of the xenosplenic perfusate in treatment of purulent peritonitis and various suppurative complications in 109 patients. A positive effect was noted (20% reduction of lethality, 1.5-3.5 times shorter period of treatment). PMID- 1302909 TI - [The correction of the glycemia level in patients with concomitant diabetes mellitus]. PMID- 1302910 TI - [The role of determining the level of middle molecules in patients in the diagnosis and treatment of suppurative-inflammatory complications after operations on the liver and pancreas]. AB - Investigations of the level of medium-mass molecules were performed in blood plasma of 52 patients in dynamics after different operations on the liver and pancreas. Significant elevation of the level of medium-mass molecules was noted in patients with pyo-inflammatory complications. The inverse relationship between the level of medium-mass molecules and the prognostic coefficient value (the ratio of the general plasma protein to the general protein of wound discharge) was revealed. The indicators of the prognostic coefficient value decreased when the level of the medium-size molecules elevated against the background of purulent complications. These data allowed to estimate the severity of purulent complications and degree of intoxication which helped to determine the correct method of treatment of patients and to timely detect pyo-inflammatory complications. PMID- 1302911 TI - [The use of clofelin as a component in cerebrospinal anesthesia]. PMID- 1302912 TI - [A method for assessing the efficacy of analgesia]. PMID- 1302913 TI - [A drug method of first aid in thermal and chemical burns]. PMID- 1302914 TI - [The 60th anniversary of the Saint-Petersburg I. I. Dzhanelidze Research Institute of First Aid]. PMID- 1302915 TI - [The surgical treatment of duodenal peptic ulcer in young patients]. PMID- 1302916 TI - [An active individualized treatment procedure for patients with bleeding stomach and duodenal ulcers]. AB - Individual methods of treatment of patients with ulcer bleedings are described. At the period from 1987 to 1990 170 patients were operated upon. Lethality was 3.1%. PMID- 1302917 TI - [The effect of the type of operation and of combined pathology on the treatment results in patients with chronic disorders of duodenal patency]. AB - The work presents results of surgical treatment of 38 patients with chronic disturbance of duodenal patency. It was established that operations aimed at the improvement of the passage of food through the duodenum, gave unsatisfactory results in remote period in 30% of cases. Operations are recommended aimed at the improvement of the passage of contents of the duodenum in combination with operations excluding the duodenum from the passage of food. Surgical correction of coexistent diseases of the digestive system is recommended. PMID- 1302918 TI - [Aspiration-lavage treatment in suture incompetence of the duodenal anastomoses and stump following gastric resection]. AB - An analysis of results of 26 patients has been made who had incompetent sutures of anastomoses and stump of the duodenum at the nearest postoperative period after gastric resection. In 14 patients (main group) aspiration-lavage method of drainage was used, in 12 patients (control group) other methods of treatment of incompetent sutures were employed. The advantage of the aspiration-lavage method of treatment over other methods is shown. PMID- 1302919 TI - [Simultaneous operations in the surgical treatment of cancer of the esophagus and cardia]. AB - In the clinic one-stage operations for cancer of the esophagus of different localizations and cardia were performed on 63 patients. The substitution of the removed esophagus was fulfilled with an isoperistaltic tube made from the greater curvature of the stomach with anastomosis on the neck or in the pleural cavity. After intrapleural plasty lethality was 21%, after total one with extracavital esophagogastroanastomoses--14%. For prevention of ischemic complications an intraoperative assessment of viability of the transplant was performed with the help of microphotoplethysmography. The authors have shown the advantage of endolymphatic route of administration of cytostatic in 25 patients as compared with the intravenous one. PMID- 1302920 TI - [The use of decompressive endoscopic operations in the complicated course of cholelithiasis]. AB - The article is based on an analysis of observation of 853 patients with complicated forms of cholelithiasis. The average age of patients was 73.5 years, two thirds of them had critical coexistent diseases. The system of treatment proposed by the authors allowed achievement of good results (lethality is less than 5%) while the methods of treatment generally accepted in surgical practice is followed by higher lethality achieving 40%. The work analyzes errors and complications of endoscopic decompressing operations and gives recommendations for their prevention. PMID- 1302921 TI - [The current problems of relaparotomy]. AB - Relaparotomy was performed in 252 of 23,232 (1.08%) patients operated upon. The most frequent cause of relaparotomy is purulent complications. These patients have immunodeficient states due to different causes (duration of the disease, old age, diabetes mellitus, toxemia, anemia, extension of the injuries, irrational administration of antibiotics). Due to it, anaerobic neclostridial infection is widely used. Its participation in the purulent process in the abdominal cavity achieves 80-90%. For prevention and treatment of purulent complications of great importance is the modern and adequate struggle against intoxication and hypoxia, correction of immunodepression, purposeful antimicrobial therapy. Problems in determination of indications for relaparotomy are emphasized and the necessity to perform it in earlier terms. PMID- 1302922 TI - [Gastric torsion]. PMID- 1302923 TI - [The surgical procedure in duodenal ulcer complicated by a choledochoduodenal fistula]. PMID- 1302924 TI - [A method for restoring digestive tract continuity after extirpation of the stomach]. PMID- 1302925 TI - [Torsion of the greater omentum]. PMID- 1302926 TI - [Rare forms of Crohn's disease]. PMID- 1302927 TI - [The radical surgical treatment of Crohn's disease of the large intestine complicated by rectal stenosis and chronic intestinal obstruction]. PMID- 1302928 TI - [Chronic calculous cholecystitis complicated by choledocholithiasis, mechanical jaundice, liver-gallbladder and gallbladder-large intestine fistulae]. PMID- 1302929 TI - [An anomaly of the descent of the bile duct in a female patient with chronic cholecystopancreatitis]. PMID- 1302930 TI - [The dynamics of the disintegration of biliary and urinary stones during shock wave lithotripsy]. PMID- 1302931 TI - [The indications for the use and the technical characteristics of gastric resection by Roux's method]. AB - Based on findings of general diagnosis in 62 patients the authors have determined indications for using Roux resection of the stomach which was used as primary operation in 22 patients and repeated operation--in 40 patients. Main indications for Roux resection were chronic disturbance of duodenal patency, chronic pancreatitis, afferent loop syndrome, reflux-gastritis. The work describes technical peculiarities of the Roux resection of the stomach with necessary observation of 6 pathogenetically substantiated rules. Results of Roux resection of the stomach are good, no evacuatory disorders of the gastric stump were noted. PMID- 1302932 TI - [Echography in the diagnosis of postoperative intestinal obstruction in children]. PMID- 1302933 TI - [A method for assessing tissue acetylcholinesterase activity in the diagnosis of Hirschsprung's disease in newborn infants]. PMID- 1302934 TI - [Splenic torsion in a 6-month-old child]. PMID- 1302935 TI - [The successful treatment of a child with a heart wound]. PMID- 1302936 TI - [Resection of the damaged liver in a child]. PMID- 1302937 TI - [The physiological aspects of the efficacy of reconstructive operations in arteriosclerosis obliterans of the lower extremities]. AB - Reconstructive operations in the aorto-iliac and femoro-popliteal segments were performed on 281 patients with obliterating atherosclerosis. An attentive examination of the patients in the nearest postoperative period and within the first 5 years has shown different efficiency of the operation in different patients. Favorable changes took place in regional hemodynamics, while disturbances retained in microcirculation and function of the extremity. Another cause of insufficient efficiency of the interventions was an initial stable suppression of tissue respiration and oxygen utilization in the extremity tissues. The dynamics was positive during a year followed after that by new symptoms of progressing disease. PMID- 1302938 TI - [False aneurysms of the vascular anastomoses after reconstructive operations on the aorta and arteries of the lower extremities]. AB - The authors have performed an analysis of examination and surgical treatment of false aneurysms of vascular anastomoses (34) in 29 patients after reconstructive operations on the aorto-iliac and femoro-popliteal segments. This late complication was found to develop in 3.3% of the patients operated upon. In 66.5% of them the aneurysms had complicated the clinical course. Multifactorial genesis of false aneurysms was confirmed. The first place among etiological factors belongs to infection. Reconstructive operations with resection of the aneurysm and restoration of blood flow were performed on 27 patients. Good results were obtained in 25 of them, reamputation of the femur and shin was made in 2 patients. The authors insist on early diagnosis and active surgical treatment of false aneurysms of anastomoses. PMID- 1302939 TI - [The surgical restoration of the function of the knee joint in patients with severe refractory posttraumatic contractures]. AB - Results of operative treatment of 100 patients with long-standing persistent contractures of the knee joint and partial defects of condyles of joint ends were studied. The treatment used allowed to obtain favorable results in majority of the patients and to return working ability to the patients. The application of perosseous apparatuses and allotransplantation make the potentialities of reconstructive surgery of the knee joint much wider. PMID- 1302940 TI - [The functional restoration of the grip in a patient following high amputation of the hand]. PMID- 1302941 TI - [The replantation of the thumb in avulsive amputations]. AB - A comparative assessment of results of operations was made in 2 groups of patients with abruption of the first finger. An analysis of immediate and long term results of operations has shown advantages of the method of replantation with heterotopic revascularization of the replanted first finger and reinnervation by means of plasty of the palmar digital nerve. PMID- 1302942 TI - [Acute intestinal obstruction as a problem in emergency surgery]. AB - An experience with treatment of acute ileus is presented. Operations were performed on 499 patients. Postoperative lethality from small intestine obstruction was 12.5%, from the colon obstruction--32.4%. The methods of treatment of different forms of intestinal ileus are described. PMID- 1302943 TI - [The intestinal suture under conditions of disordered blood supply]. AB - Under conditions of disturbed blood supply, irrespective of the method of anastomosing, the trophicity of tissues in the zone of suture is sharply disturbed. These alterations are especially pronounced after using multi-row suture when healing develops very unfavorably. In hypoxia of tissues a one-row everting suture made by the author's method with a removal of mucosa and preservation of submucosa provides more favorable conditions for healing of the wound in the place of anastomosis. The method of intestinal suture is described. PMID- 1302944 TI - [The efficacy of the conservative treatment of patients with acute appendicitis on board ships at sea]. AB - Under study was efficiency of conservative treatment of 247 patients with acute appendicitis on ships in the sea depending on the age of patients, clinical manifestations of the disease, volume of medicamentous therapy and time of taking medical advice. It was established that conservative treatment is most effective if started within the first 6 hs from the beginning of the disease and antibiotics were used in combination with spasmolytics, antihistamines and sulfanilamides. Patients treated conservatively had pronounced inclinations to delimiting the inflammatory process in the abdominal cavity. PMID- 1302945 TI - [Diagnostic and therapeutic laparoscopy in acute cholecystitis in middle and old age]. AB - Laparoscopic decompression of the gallbladder in elderly and senile patients having acute cholecystitis and in patients with severe coexistent diseases allows arresting the acute inflammatory process in the gallbladder, reducing the amount of forced operations which are extremely dangerous for this contingent of patients. Sanitation of the gallbladder with the electrolytic silver solution and irradiation of the bladder mucosa with laser is highly effective. Microcholecystostoma performed with a catheter having a diameter not less than 2.5 mm maintains adequate decompression of bile ducts and allows performing complete examination of them. PMID- 1302946 TI - [The functional assessment of the late results of surgical treatment in lung cancer]. AB - Results of a complex clinico-functional examination of 48 patients after resection for lung cancer 8-10 years ago are presented. The satisfactory pumping function of the heart was revealed with practically normal volumes of the cardiac output. Among patients subjected to resection of a lobe of the lung two groups were determined: with relatively satisfactory parameters of the function of external respiration and blood circulation and with a pronounced degree of strain of the functioning of these systems. PMID- 1302947 TI - [The clinico-functional assessment and work capacity of patients undergoing repeated operations on the mitral valve]. AB - A complex of examinations (ECG, echocardiographic and X-ray evaluations of heart volumes and cavities, treadmill-test) was performed in 82 patients before and after reoperations on the mitral valve. The type of recorrection was found to be associated with the degree of positive dynamics of the results. The data obtained contradicted to hyperdiagnoses of primary medical-labor examination commission establishing the II group of invalidism in 86 +/- 4% (M +/- m) of the examined patients. As a result of an analysis of all the data obtained the number of such patients was reduced up to 34 +/- 5%. A new approach to solving the problem of medical-labor examination was shown to be necessary for patients reoperated for mitral disease of the heart. PMID- 1302948 TI - [Variants in the distribution of the vertical reflux of blood through the pelvic veins and the routes for its transmission to the veins of the lower extremities in patients with varicose veins]. AB - An analysis of complex clinical and phlebographic examinations of 60 patients with the varicose disease has been made. Twelve variants of ways of spreading vertical reflux of blood along the pelvic veins have been established and two ways of its transmission to the lower extremity veins: a direct way of reflux from the iliac to femoral vein and an indirect ways of reflux--from tributaries of the iliac vein to those of the femoral vein. To eliminate the direct reflux the operative correction is necessary of the valve of the common femoral vein located inferior to the inguinal ligament. For patients with the indirect way of reflux ligation of the injured communicating veins of the gluteal area and femur, dissection of the varicose external labial veins are indicated. PMID- 1302949 TI - [The surgical treatment of Dupuytren's contracture]. AB - Treatment of 129 patients with palmar fibromatosis was performed; all the men were from 20 to 63 years old. In 56 patients (1st main group) operation of aponeurectomy was performed with the help of an ultrasonic scalpel (USS), in 53 patients (2nd main group) the operation was made with the help of the microsurgical technique (MST), 30 patients (a control group) were operated upon by usual methods. The use of USS and MST were followed by excellent (92.6%), good (2.1%) and satisfactory (5.3%) long-term results. PMID- 1302950 TI - [Objective methods for controlling the course of the wound process in the surgical treatment of suppurative fistulae and abscessing epithelial cysts in the sacrococcygeal region]. PMID- 1302951 TI - [Traumatic disease in wounded patients]. AB - Results of clinico-physiological, pathobiochemical, immunological and hemocoagulative studies performed at the postshock period in 186 patients with battle wounds have shown their coincidence with data obtained in critical mechanical trauma of peace-time. A conclusion is made that critical gunshot wounds are followed by trauma disease having main regularities similar to those in a critical mechanical trauma of peace-time. One can speak only about specific features of battle injuries, but to distinguish "wound disease" as an independent clinical form is thought to be illegal. PMID- 1302952 TI - [The use of the "internal autotransfusion" method in complex shock-control measures at the prehospital stage]. AB - Fifty-three patients with traumatic shock were injected 200-400 ml of a 10% solution of sodium chloride in combination with 100 ml of the 40% solution of glucose. The continuous, for 1-2 h, elevation of arterial pressure, increased minute blood circulation volume, cardiac index, stroke volume were noted. At the same time base deficiency in blood was growing. So, in the last 5 patients the infusion therapy at the prehospital stage was completed by injecting 200 ml of 3% sodium solution and the acid-base state in them was thus leveled. When using the "internal autotransfusion" lethality was reliably less than in patients who were treated by routine (polyglucon, gelatinole) infusion therapy. PMID- 1302953 TI - [A procedure for infusion-transfusion therapy and autohemodilution in severe trauma and shock (apropos the article by B. N. Salamatin et al., The use of the "internal autotransfusion" method in complex shock-control measures at the prehospital stage)]. AB - The infusion of hypertonic solution is thought by the authors to be effective due to its reflectory action for treatment of patients who are in the state of anaphylactic and cardiogenic shock. This method seems to be expedient for massive blood loss under conditions of prehospital medical aid to victims with very low level of arterial pressure, with craniocerebral trauma and critical trauma of the chest. PMID- 1302954 TI - [The successful treatment of rupture of the liver with injuries to the hepatic vein and vena cava inferior in a victim with shock-producing combined trauma]. PMID- 1302955 TI - [A comparative evaluation of the results of treatment by different methods in fractures of the femoral and tibial condyles]. PMID- 1302956 TI - [The use of external fixation apparatus in injuries to the hand bones]. AB - An analysis of experimental studying the stability of osteosynthesis and clinical application of apparatuses of external fixation in 282 patients with fractures and sequellae of traumas of the bones and joints of the hand is presented. Main conditions influencing stability of fixation of the hand bones were determined. A universal complex of details is recommended which allows to make the optimum construction of the device as applied to the specific kind of trauma. It was proved that choice of the individual construction of the apparatus considerably widened the scope of using the method of external fixation and improved results of the treatment. PMID- 1302957 TI - [Femoral neuralgia after reconstructive operations on the arteries of the lower extremities]. PMID- 1302958 TI - [Allograft tenoplasty in ventral hernias]. PMID- 1302959 TI - [The pathogenetic and clinical grounds for the advantages of nondrug procedures in the preoperative preparation of patients with diffuse toxic goiter]. AB - An analysis of 615 patients operated upon for diffuse toxic goiter is presented. In 148 of them (24%) preoperative preparation was made with the help of nonmedicamental methods (extracorporal hemosorption, hyperbaric oxygenation (HBO), plasmapheresis). The state of euthyroidism was controlled according to their clinical symptoms and was verified by radioimmunological studies of triiodothyronine (T3), thyroxin (T4), thyrotropine (TTG). Indicators of corticosteroid hormones, thyrostimulating antibodies, antigenic HLA structure and antioxidative activity of different media of blood were also determined. The estimation of the data obtained as compared with results of morphological examinations allowed a conclusion that the above nonmedicamental methods in patients with diffuse toxic goiter are pathogenetically substantiated. Clinical expedience of their use is obvious. No lethal outcomes or complications resulted from using hemosorption and HBO. Single complications took place resulting immediately from catheterization of large venous vessels. Long-term results from 3 to 9 years have shown that recurrences of the disease in patients given nonmedicamental preoperative preparation were met much more rarely as compared with patients who obtained routine preparation (1.4% and 5.4 correspondingly). PMID- 1302960 TI - [The potentials of perfusion methods in the combined intensive treatment of peritonitis]. PMID- 1302961 TI - [Intraoperative changes in the peripheral circulation with different methods for reconstructing the arteries of the extremities]. AB - An examination of 192 patients with obliterating atherosclerosis of lower extremities was made who had different reconstructive operation. Intraoperative measurements of oxygen strain in the foot skin and rheography of the shin have shown that temporary compression of large arteries when making vascular anastomoses cause ischemia of extremities, whose degree and duration is dependent on the technique of the technique of the intervention. Advantages of the method of transprosthetic aortotomy such as less duration and lower degree of ischemia were shown. The possibility was revealed to prognose nearest results of treatment for changing regional hemodynamics and oxygenation of tissues at the moment of termination of the operation. PMID- 1302962 TI - [The diagnosis of foreign bodies left behind in the pleural cavity during operations]. PMID- 1302963 TI - [Diagnostic errors and difficulties in acute appendicitis in women]. PMID- 1302964 TI - [The possibilities for using enterosorption in the surgical clinic]. PMID- 1302965 TI - [The current treatment of inguinal hernias]. PMID- 1302966 TI - [The types of surgical operations in treating pathological obesity]. PMID- 1302967 TI - [The healing effect of extracorporeal circulation]. PMID- 1302968 TI - [Current problems in the diagnosis and surgical treatment of rare developmental defects of the lungs]. AB - The author analyzes questions of diagnosis and surgical treatment of 168 patients with rare malformations of the lungs which made up 5.6% of the general amount of patients with surgical nonspecific diseases of the lungs and 36.1% among all defects of development of the lungs. It was established that diagnostics of rare defects of development of the lungs might be of full value but when using a complex of roentgenological, bronchiological and functional methods of examination. Surgical treatment of rare defects of the lung development is indicated to 86.1% of the patients and must be performed till the progressing of secondary alterations, when disturbances of ventilation and oxygenation are observed, there is blood flow shunt disturbances of hemodynamics of the pulmonary circus of blood circulation. PMID- 1302969 TI - [The effect of temporary endobronchial occlusion on pulmonary gas exchange in the treatment of pyopneumothorax]. AB - An estimation of changes of main hemodynamic, biochemical and laboratory indicators and the function of external ventilation was fulfilled when performing temporary endobronchial occlusion at the level of lobular and main bronchi in 37 patients with pneumothorax. Favorable changes were established in the systems of blood circulation and external ventilation in occlusion of lobular bronchi. Grounds are given for the necessity of intensive anti-inflammatory treatment, oxygenation and maintenance of cardiodynamics in occlusion of the main bronchus. PMID- 1302970 TI - [The prognostic assessment of the reversibility of myocardial dysfunction in patients with ischemic heart disease after aortocoronary bypass]. AB - Forty-six patients with ischemic heart disease with considerable dysfunction of the myocardium were subjected before operation of aortocoronary shunting to veloergometry with calculation of indices of the central hemodynamics by the method of tetrapolar rheoplethysmography, echocardioscopy before and after taking nitroglycerin. Close interrelation was noted between the increase of the stroke volume during veloergometry, increased fraction of output after taking nitroglycerin and improved contractile capacity of the myocardium after aortocoronary shunting. PMID- 1302971 TI - [The hemostatic effect of vagotomy in acute gastroduodenal ulcers complicated by massive hemorrhage]. AB - The clinico-experimental investigation has shown high efficiency of the bilateral subdiaphragmatic truncal vagotomy in treatment of patients with acute gastroduodenal ulcers complicated by massive hemorrhage. The haemostatic effect of the operation is related to the inhibited acid gastric secretion, proteolytic activity of the intragastric content as well as to the activation of serotonin containing cells and increased tonus of the sympathetic nervous system, which is responsible for gastric vessel spasm, shortens time of bleeding, increases the amount of thrombocytes and their aggregation. When vagotomy with interventions draining the stomach is not possible, suturing (dissection) of bleeding acute ulcers is recommended in combination with prolonged novocain blockade of vagus nerves. PMID- 1302972 TI - [The digestive activity of the chymus in the gastric stump in postgastrectomy peptic ulcers]. AB - Forty-two patients with postgastroresection peptic ulcers of the zone of gastrojejunal anastomoses were examined. The cause of the appearance of the ulcers was the action of aggressive content of the gastric stump on the jejunum in the area of anastomosis. "Vagal" peptic ulcers were found by the gastrocepin test. After operations reducing the stump acidity healing of all the ulcers was noted. In achlorhydria of the stump the digestion in it is realized due to reflux at the expense of pancreas proteinases. PMID- 1302973 TI - [The preoperative morphological diagnosis of hepatobiliary and pancreatoduodenal cancer]. AB - Morphological investigations at the preoperative stage were performed in 94 patients. The morphological diagnosis was made on the basis of findings of duodenal biopsies, cytological investigations of the bile and aspirate from the Vater's papilla ampulla, endocholedochal and percutaneous biopsies with the express cytological monitoring. Recommendations are given on the programs of preoperative morphological diagnosis of carcinoma of Vater's papilla. PMID- 1302974 TI - [Spontaneous rupture of the esophagus]. PMID- 1302975 TI - [Simultaneous operation in a female patient with hepatic echinococcosis, calculous cholecystitis, umbilical hernia, uterine fibromyoma and polycystic ovaries]. PMID- 1302976 TI - [The procurement of demineralized cranial transplants and their clinical use]. AB - Demineralized cranial transplants of allogenic origin when transplanted to 49 neurosurgical patients with defects of the skull cap of not more than 50 cm2 area gave positive results by liquidating the corresponding symptoms. High bioplastic quality of such transplants allow them to be recommended for wide use in clinics. PMID- 1302977 TI - [Relaparotomy in closed abdominal trauma]. PMID- 1302978 TI - [Microsurgical autotransplantation in gunshot wounds of the extremities and their sequelae]. AB - An experience with treatment of 108 patients with extensive deep defects of extremity tissues was generalized. Such wounds made up 42.3% of the total number of patients with wounds of extremities. The introduction of microsurgical autotransplantation of tissues allowed to shorten the terms of medical and social rehabilitation, to reduce invalidism of the patients and to lower the cost of treatment. PMID- 1302979 TI - [A penetrating wound of the heart complicated by a left ventricular aneurysm and an aortopulmonary fistula]. PMID- 1302980 TI - [Forced operations on the vena cava inferior]. PMID- 1302981 TI - [The use of photomodified blood in oncology]. AB - Under study was the influence of different regimens of blood photomodification on the course of the tumor process. Experiments were carried out on 460 syngeneic mice with a model of Lewis adenocarcinoma of lungs and melanoma B 16. It was established that the influence of APMB on the course of the tumor process is dose dependent and when specially selected the regimen of APMB may have an antitumoral effect. The transfusion of the photomodified donor blood may facilitate the suppression of antitumoral immune reaction of the recipient organism. PMID- 1302982 TI - [Quantum hemotherapy in the treatment of chronic postembolic pulmonary hypertension]. AB - Based on studying 34 patients, the authors made a conclusion that transfusion of UVI autoblood improves the pulmonary blood circulation, increases blood oxygenation and deformability of erythrocytes, decreases blood viscosity. PMID- 1302983 TI - [The therapeutic efficacy of the blood substitute polyoxydin in experimental hemorrhagic shock]. PMID- 1302984 TI - [Rare posttransfusion complications and their prevention]. PMID- 1302985 TI - [A new modification of the hand suture of the bronchus with a mathematical validation in pulmonectomy]. PMID- 1302986 TI - [A comparative evaluation of the use of vernix caseosa and solcoseryl in treating patients with trophic ulcers of the lower extremities]. PMID- 1302987 TI - [Foreign bodies in the organism]. PMID- 1302988 TI - [The diagnosis of Hashimoto's goiter and thyroid cancer]. PMID- 1302989 TI - [The characteristics of the precision technic in the surgical treatment of benign lung neoplasms]. PMID- 1302990 TI - [Experience in the surgical treatment of osteomyelitis]. PMID- 1302991 TI - [The terminology in traumatology]. PMID- 1302992 TI - [The indications for lymphogenic antibiotic therapy in peritonitis and its efficacy]. PMID- 1302993 TI - [The diagnosis and treatment of pancreatic ectopy]. PMID- 1302994 TI - [The hand of the surgeon]. PMID- 1302995 TI - [The colostoma in proctology]. PMID- 1302996 TI - [The committee for the study of gunshot osteomyelitis during the blockade in Leningrad]. PMID- 1302997 TI - [Simultaneous transplantation of the pancreas and kidney in diabetic uremia]. PMID- 1302998 TI - [The treatment of tumors of the maxillofacial area and neck with the continuous wave CO2 laser]. PMID- 1302999 TI - [The role of morphological study methods in the diagnosis of Hirschsprung's disease in children]. PMID- 1303000 TI - [An immunoelectron microscopic study on the development of the antibody-producing cells in the guinea pig popliteal lymph nodes]. AB - The pre-embedding immunoelectron microscopic method was used to study the development of antibody-producing cells in the guinea pig popliteal lymph nodes of 2, 3, 5, 8 and 10 days after a second challenge with horseradish peroxidase. The results indicated that the antibody activity was located in the perinuclear space, the endoplasmic reticulum and Golgi complex. According to the cellular developmental stages and the characteristics of distribution of the antibody activity, the antibody-producing cells (APC) were divided into four types: (1) Type I cells (lymphocytes) exhibited many positive granules throughout the cytoplasm; (2) Type II cells (proplasmacytes) contained many positive granules and positive short bars, some of them were parallel; (3) Type III cells (proplasmacytes) contained numerous parallel positive lamellae in cytoplasm; (4) the parallel lamellae in cytoplasm of type IV cells (plasmacytes) were arranged into a network-endoplasmic reticulum. According to the kinetic change from granules, short bars to parallel lamellae and the network, the results indicated the developmental course of AFC from lymphocytes, proplasmacytes to plasmacytes. PMID- 1303001 TI - [The production of IL-2, IL-6 in relation to the functional development of NK cells in human fetal spleens]. AB - The production of IL-2, IL-6 by fetal splenic mononuclear cells (FSMC) and relationship between them and the ontogenetic development of natural killer cell function were studied in human fetal spleens. As a results, before 20 weeks of gestation, both IL-2 and NK cell activities were not measured, but IL-6 was done. It was found that IL-2, IL-6 and NK cell activities were increased with the gestational age, and shown that there were linear positive correlation between the activities of three ones above (r > 0.86). Before the birth, the induced IL-2 activity was the same as adult levels (p > 0.05), although both IL-6 production and NK activity in fetal spleens were significantly lower than that in adults (p < 0.01). Lastly, the production of IL-2, IL-6 in relation to the functional development of NK cells during the embryonic development was discussed. PMID- 1303002 TI - [The role of p53 gene in the switch of U937 leukemic cells from growth into differentiation]. AB - The expression of p53 gene has been found to be regulated during the induction of differentiation of U937 leukemic cells into mature macrophages by recombinant human granulocyte- macrophage colony stimulating factors (rhGM-CSF) We showed here that the increased expression of p53 seemed to be necessary for the differentiation of U937 cells induced by rh-GM-CSF. The inhibition of p53 expression by a p53 antisense oligodeoxynucleotide lead to the significant decrease of formation of mature macrophages from U 937 cells in the presence of rhGM-CSF. By contrast, the p53 sense oligodeoxynucleotide had no any effect. Furthermore, we have analysed the growth of U937 cells in the presence or absence of rhGM-CSF. The results showed that rhGM-CSF dramatically inhibited the growth of U 937 cells in the cultures. At the same time, the antisense inhibition experiment demonstrated that the inhibition of p53 expression partially diminished the growth-inhibitory effect of rhGM-CSF on U 937 cells. These results suggested that the p53 was required for the initiation of rhGM-CSF-induced differentiation of U 937 cells on one hand, and the inhibition of cell growth on the other hand. Thus we deduce that the increased expression of p53 induced by rhGM-CSF may be a coupling event of switch of U 937 cells from growth into differentiation. PMID- 1303003 TI - [Effect of gossypol on the proliferation of rat prostate cells studies in vivo and in vitro]. AB - The effect of gossypol on prostate cells of rat was studied both in vitro and in vivo. For in vivo study, mature male Sprague Dawley rats were given gossypol orally, 5 mg/day, 5 times a week for one month. Then the prostates were examined histologically. By adding gossypol to the culture system directly, NbE-1 cells were used in vitro study. Several parameters, including histological structure, cell growth, DNA synthesis and mitotic cycle of cells were measured by different methods. The prostate size and weight in experimental rats decreased and significant differences between acini in controls and gossypol treated animals were noted. Acini of control prostate were full of protruding folds constituted by columnar epithelial cells, whereas, the most of the acini in treated animals were composing of cubic or square epithelial cells and epithelial folds were rarely seen. Thus, acini with normal appearance were about 14% less than that in controls. In the in vitro experiments, both cell proliferation and DNA synthesis decreased from 0 to 80% and from 0 to 90% respectively, when the concentrations of gossypol were increased from 0 to 20 micrograms/ml. It seems that 10 micrograms/ml of gossypol could cause the most significant inhibition in these two cellular functions. The cell mitotic assay showed that in treated groups, the cell number of S phase was decreased from 43 to 31%, this fact indicated that the inhibition on cell proliferation caused by gossypol might be due to preventing cells to enter S phase. Besides, inhibition effect on the proliferation of prostatic epithelial cells was dosage dependent and related to the duration of treatment. PMID- 1303004 TI - [The distribution and changes of lectin receptors in developing mouse cornea]. AB - Using ConA-HRP and RCAI-HRP as probes, the distribution and changes of glycosides in mouse cornea were studied during pre- and postnatal development. Mannose residues were distributed mainly in stroma and endothelium, sialic acid residues in epithelium and galactose residues in both epithelium and stroma. Mannose residues in stroma showed an increased density toward endothelium before and after birth. Sialic acid and galactose residues were concentrated gradually at the corneal epithelial surface in accompanied with the development of cornea. The embryonic day 13 was the starting day to synthesize glycoconjugates from fibroblasts of mouse cornea. PMID- 1303005 TI - [The synaptic architecture of propriospinal neurons in cultured mouse spinal cord]. AB - An electron microscopic analysis of the synaptic architecture in propriospinal neurons of cultured fetal mouse spinal cord has been undertaken. The size of the perikarya in the cultured spinal cord represents a range from small- to medium sized neurons, which form many synapses each other. There are many axo-dendritic and axo-somatic synapses in the culture but direct dendro-dendritic apposition is rarely seen. Four morphological types of synaptic boutons, S, F, M and G are classified according to criteria used by previous investigators. The ultrastructural details available suggest that the propriospinal neurons receive synaptic input from propriospinal fibers through simple synapses. It may indicate that their impulses can be controlled only postsynaptically. PMID- 1303006 TI - [Cell kinetic analysis and treatment planning in epidermoid tumors of the head and neck]. AB - Cell kinetic parameters were evaluated using the method based on in vivo incorporation of Bromodeoxyuridine (BrdU) and flow cytometric (FCM) analysis in 30 human epidermoid head and neck tumors from oropharynx, oral cavity, rhinopharynx, larynx and lips. BrdU was injected four/six hours before the obtainment of multiple bioptic samples from the tumor tissues. The flow cytometric method was carried out on 70% ethanol fixed cell suspensions based on established protocol for the simultaneous evaluation of DNA content and BrdU uptake using anti-BrdU monoclonal antibodies. We have evaluated the following FCM parameters: DNA ploidy, the degree of DNA aneuploidy (DNA index), Labelling Index (LI), duration of s-phase (Ts) and tumor potential doubling time (Tpot). LI values ranged from 1.5 to 20% with a median value of 10%. The median LI of DNA diploid tumors was 5.4% compared to 14% in DNA aneuploid tumors. Ts values ranged from 8 to 11, the median value being 10 hours. Tpot values ranged from 2 days to 16 days, the median Tpot being 5 days. The large heterogeneity of all these parameters indicates that these tumors may have a different degree of biologic aggressiveness (9). Tpot values did not correlate with DNA ploidy nor with lymph node metastasis status. Tpot values did not correlate in a statistically significant manner with degree of differentiation although shorter Tpot were more frequently observed in moderate or poorly differentiated tumors. Our study shows that the FCM-BrdU technique in vivo is feasible in a clinical setting to evaluate the proliferative behaviour of head and neck tumors, before any specific therapeutic decision is taken after surgery is performed. It is likely that tumors with more aggressive biological behavior, as indicated by LI > 15%, DNA aneuploidy and Tpot < 5 days, may benefit from more aggressive therapies such as accelerated regimeus of radiotherapy and/or other multimodal therapies in respect to tumors with slow growth rate (LI < 15%), DNA diploidy and Tpot > 5 days. So far, however, it still remains to be demonstrated from randomized clinical trials if the knowledge of such individualized cell Kinetic parameters really can help to choose the most effective therapy for every individual patient. PMID- 1303007 TI - [Role of beta-carotene in the prevention of genotoxic damage in patients undergoing radiotherapy. Monitoring by the micronucleus test in exfoliative cells of the oral cavity]. AB - Radiotherapic treatment of patients with carcinoma usually causes genotoxis damage. This has been studied recently using the test of micronuclei in esfoliated cells. This test presents methodologic advantages in compared with the classic citogenetic analysis and as it is carried out on esfolieted cells from the oral cavity it faithfully reflects the genotoxic damage undergone by the cells of the basal layer of the epitelium. The preliminary result obtained so far have confirmed the anticlastogenic activity of beta-carotene in fact, the frequence of micronuclei in esfolieted cells from the oral cavity in patients undergoing radiotherapy or undergoing treatment with beta-carotene is inferior to that of patients undergoing treatment with beta-carotene is inferior to that of patients undergoing radiotherapy without the subministration of carotenoids. Treatment with carotenoids does not influence the therapeutic efficiency of radiotherapy treatment. Therefore, the results seem to confirm that indirect ossidaction processes are involved in the mechanism of the clastogenic action of radiotherapia. The carotenoids seem to be able to contrast validly this undesirable effect without interfering with the desirable therapeutic effect. PMID- 1303008 TI - [Bovine costal cartilage as material for otologic reconstruction: anatomo functional results]. AB - The Authors present their experience in using bovine cartilage as otological material reconstruction. Cartilage of the ribs is to collect from selected bred cattle and is first placed in an antibiotic solution for 3 days and then in a 70% ethyl alcohol in which it is stored for 20 days before being utilized. One hundred-nineteen cartilage heterografts have been implanted in the middle ear since January 1989. We report the results of 86 cases which were included in a followed study for at least 12 months. Bovine cartilage was used in 47 canal up techniques, 28 canal down techniques and 11 anatomic and functional rehabilitation of old radical cavities. The result prove most encouraging. In 74 cases we observed good anatomical results characterized by a new, intact eardrum with no sign of inflammation or a cavity lined with normal epithelium. No extrusion was found. Removal of cartilage implanted after a year enabled us observe the high tolerance of the graft and to carry out further histological examination. The histological findings indicated normal and intact cartilagineous matrix, lined with fibrous tissue and mucosa with no evidence of condrocytes. In cases in which the heterografts were utilized for ossiculoplasty, the post operative air-bone gap was 11.1 dB and the mean hearing gain was 26.3 dB. Moreover, bovine cartilage is easily obtainable and available in pieces of sizes necessary for specific purposes in otologic surgery. Cartilage heterografts might well be a good alternative to autologous and homologous cartilage grafts. PMID- 1303009 TI - [Interaction between continuous and impulse noise: anatomic and functional evaluation in relation to the intensity of the exposure]. AB - Interaction between continuous and impulse noise was studied. One group of chinchillas was exposed to octave band of noise of 0.5 kHz 95 dB SPL intensity. Three groups were exposed to impulse noises of 113, 119 and 125 prak SPL emitted at 1 imp/sec, 1 imp/4 sec and 1 imp/16 sec respectively. Three groups were exposed to noise created by a combination of above continuous and impulse noises. All exposures lasted for 5 days. Hearing thresholds were measured in 35 animals using auditory evoked potentials. The combined continuous and impulse noises showed equal energy contents, but the groups exposed to 119 and 125 dB impulse noise intensities developed an exacerbation of PTS and cell hair loss. Therefore, the critical level, under which the damage associated with noise exposure is related to the total noise energy (Equal Energy Hypothesis) was reduced when impulse noise was added to continuous noise. PMID- 1303010 TI - [Open rhinoplasty: indications and limits of a controversial method]. AB - As Aufricht has said, rhinoplasty is "... an easy operation to do, but it is hard to get good results". As it clearly observed in ENT rhinoplasties which deal with severe and combined defects of the nose which result in functional impairment. The aim of this study was to analyse complications in a personal series of open rhinoplasties as well as those in literature in order to standardize different surgical approaches possible in correcting various nasal deformities, divided according to a personal classification. Other than the classical intramucosal technique (following Roe, Joseph and Weir), the more conservative extramucosal operation (described by Jost and Aiach) and the more aggressive external approach are available to the surgeon. Intramucosal rhinoplasty is still the most dependable and widely used technique. However open rhinoplasty which brings about complications in less than 10% of the procedures, offers clear-cut advantages if employed following precise indications. In our experience, the main indications for open rhinoplasty are: severely crooked nose, above all of the II and III arch: crooked nose with saddle deformity; asymetrical defects (including those due to a cleft lip); 50% of the secondary rhinoplasties (excluding minor procedures). PMID- 1303011 TI - [Analysis of the cellular infiltrate and epithelial class I and II molecular expression in edematous type nasal polyps]. AB - Although in the last few years histopathological, immunohistochemical and immunological studies on nasal polyps have been carried out by several Authors, the etiology of these formations still remains unknown. Nasal polyps have a very characteristic structure and have been classified in three histologic types: edematous, glandular and fibrous. In the present report, 11 nasal polyps of edematous type, representing 61% of total number of collected polyps, were studied employing immunohistochemical methods. All the examined polyps were similar in histology and positivity pattern for HLA molecule expression. The edematous core appeared infiltrated (149 cells/mm.2) mainly by eosinophils (> 90%), whereas the peripheral subepithelial connective tissue contained cellular clusters (416 cells/mm2.) made up of different subsets of hematic cells (30.8% were monocytes-macrophages and 48.6% were lymphocytes largely represented by CD4+ cells). On the contrary, mast cells were quite rare (on the average 1.7 cells/mm2.) and located near T cell clusters. The epithelial positivity for HLA DR and HLA-A,B,C molecules showed a characteristic discontinuous pattern. In the same patient, controlateral nasal mucosa showed a histological structure very similar to that of polyps. The above data suggest that the presence of polyps is the result of an inflammatory process brought about by a complex array of cellular and humoral components. PMID- 1303012 TI - [Cystic parotid lesions in HIV infection]. AB - The appearance of parotid lesions of cystic aspect with a HIV's infections has been described in the past by foreign Authors above all coming from USA and from Africa. Similar cases has been recorded in France but only among children. The Authors report a casuistry constituted by five male sex's and white race's subjects, everyone HIV positive, suffering from mono or bilateral benign lymphoepithelial cysts. Every patient under examination presented a positive history because of the use of intravenous drug. Four of the five subjects underwent a surgical treatment of parotidectomy. Echotomography, CT and RM scanning seem to be the more sensitive diagnostic techniques. The peculiar histopathologic aspects allow us to differentiate these lesions both from the classical benign lymphoepithelial cysts and from the Warthin's tumor. The increase of the signalling of these cases seems to be connected with the progressive diffusion of the infection and with major survival of the patients thanks to chemotherapy. The majority of the Authors is agreed to recommend the surgical treatment for the possible malignant degeneration of this kind of forms. A careful clinical and diagnostic analysis of every patient with parotid swelling, above all if at risk for HIV's infection, is strictly necessary. PMID- 1303013 TI - [The Lorenzo syndrome (Lorenzo de' Medici)]. PMID- 1303014 TI - The life and work of academician Dimiter Orahovats (1892-1992). PMID- 1303015 TI - Conduction velocity of antigravity muscle action potentials. AB - The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles. PMID- 1303016 TI - 4-Aminopyridine and tetraethylammonium-induced changes in action potentials of unmyelinated axons. AB - The effects of different concentrations of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the intra- and extracellular action potentials (ICAPs, ECAPs) of unmyelinated axons of Lumbricus terrestris were studied. The results showed different sensitivity of the axons to both potassium current blockers (4-AP and TEA), added to the medium. 4-AP led to spontaneous and single stimulus- evoked repetitive activity, manifested as a slow "burst" action potential propagation like "plateau" ICAP with oscillations. The ICAP duration of the TEA-treated axons increased mainly at the expense of the repolarization phase which reflected the increased duration of the ECAP recorded at long radial distances. The amplitude of the ICAPs after treatment with both blockers was decreased to 20% as compared to the controls (untreated axons) and ECAPs decreased to 40% in the TEA-treated axons. The conduction velocity (CV) of the action potentials was not significantly changed. The calculated total ionic current during the action potential upon TEA treatment was decreased and the duration of the outward phase was prolonged. PMID- 1303017 TI - Investigation of antiischemic properties and mechanism of action of azacrown ether derivative. AB - The influence of the azacrown ether derivative benzylaza-15-crown-5 on myocardial tolerance to ischemia and on the functional state of the zone of myocardial ischemia during coronary artery occlusion was investigated in experiments on anaesthetized open-chest cats. The compound tested produced a dose-dependent antiischemic effect and prevented the development of myocardial ischemia. In experiments on isolated guinea-pig papillary muscle benzylaza-15-crown-5 inhibited the first and second components of the isoproterenol-induced muscle contraction. The compound decreased the maximal contraction force and had no effect on the cardiac cycle duration and on the time necessary for reaching maximal tension. It is suggested that the protective effect of benzylaza-15-crown 5 during myocardial ischemia is mediated through the inhibition of calcium release from the sarcoplasmic reticulum. PMID- 1303018 TI - Stance does interfere with movement related brain potentials. AB - Movements of the upper limb are well known to be preceded by electromyographic activity in leg and trunk muscles known as postural preadjustment. Brain potentials preceding the actual commencement of voluntary displacement were also described. The relationship between the occurrence of these two electrophysiological phenomena was investigated by performing two types of movement in three different body positions. Healthy subjects were free standing, sitting and standing with backsupport. When fast forward arm elevation was executed, the preceding Bereitschaftspotential was higher in amplitude at 500 msec before EMG onset and alongside midline scalp leads during sitting. The amplitude at 150 msec, immediately preceding movement, did not show significant differences related to body positions and there was no contralateral dominance. When index finger flexion was performed, it did not yield differences in the Bereitschaftspotential between sitting and standing positions. These findings suggest the existence of two separate stages of the preparatory process and an influence of the muscle mass involved in the stance perturbation during voluntary movement. PMID- 1303019 TI - [The new study plan of the Faculties of Medicine of the Universidad Complutense and the Universidad Autonoma of Madrid]. PMID- 1303020 TI - [The new study plan of the Faculty of Medicine of the Universidad Autonoma of Madrid]. PMID- 1303021 TI - [Hormonal inducers of milk production: BST, oxytocin and derivatives]. PMID- 1303022 TI - [The effect of rheumatoid arthritis in the life and work of 3 great painters: Auguste Renoir, Raoul Dufy and Alexis Jawlensy]. PMID- 1303023 TI - [Autotransplantation of the parotid to the sella turcica after hypophysectomy in the rat]. PMID- 1303024 TI - [Human lactation]. PMID- 1303025 TI - [The brain, hunger and satiety]. PMID- 1303026 TI - [Alcohol dependence. The personality of the alcoholic]. PMID- 1303027 TI - [In memoriam Cristino Garcia Alfonso]. PMID- 1303028 TI - [A brief historical outline of the Real Academia Nacional de Medicina]. PMID- 1303029 TI - [In memoriam Bonifacio Piga Sanchez-Morate]. PMID- 1303030 TI - [In memoriam Vicente Gilsanz Garcia]. PMID- 1303031 TI - Veterinary drug surveillance. AB - The possible adverse effects of the application of veterinary drugs are considered with special reference to their illegal use or misuse in the different categories of animals (pet, sporting, food-producing). The risks of unacceptable drug residues in animals and their products, the environment and man are taken into consideration. The need is stressed for proper veterinary surveillance by previous assessment of priorities such as animals' health status, economic aspects, quality of food of animal origin, safeguard of the environment. PMID- 1303032 TI - Veterinary pharmacovigilance in the European context. AB - Pharmacovigilance (or pharmaco-surveillance) is the surveillance of adverse drug reactions (ADRs) which are noxious and of unintended reactions which occur at doses normally used in animals in accordance with the terms of the marketing authorization. From this definition, the scope of veterinary pharmacovigilance should be clearly defined, especially with regard to associated problems of lack of efficacy, resistance, effects in man, residues, etc. Priorities should be established concerning adverse effects in animals in order to set up an operational system. Methodological tools are being developed such as causality assessment, thesaurus, data banks, alert systems. The situation of veterinary pharmacovigilance in countries is very different. The existing systems are based on two different conceptions: a pharmacovigilance of the administrative type, made by authorities; a pharmacovigilace of the interactive type, made in veterinary universities, linked with the authorities. In industry, the importance of pharmacovigilance is increasing; collaborations have been set up but should certainly be developed. Finally, the sensitization of the veterinary practitioners, which play a key-role in the system of spontaneous reporting of ADRs, is to be developed in many ways: interaction during or after the report, publication of data, concrete actions, improvement of side-effect warnings and prevention, etc. Veterinary pharmacovigilance should be a very interesting area of cooperation between the field, universities, industry and regulation authorities. PMID- 1303033 TI - The role of multigeneration studies in safety assessment of residues of veterinary drugs and additives. AB - Multigeneration studies investigate the impact of a chemical on the reproductive function of laboratory rodents following continuous exposure of several (usually 3) generations. Such tests detects the presence of effects sensitively and efficiently; however, it may be necessary to add satellite groups to the basic protocol and/or to undertake more specific studies in order to investigate the nature of the effects observed. The possible enhancement of the chemical's impact along the generations and the use of apical endpoints (fertility, pup mean weight and survival, etc.) make multigeneration tests apt to reveal the cumulative action of minor, detrimental hits. Therefore, they appear especially important in the safety assessment of chemicals not expected to be markedly toxic, like many veterinary drugs or feed additives. The present paper reviews the role played by the data drawn from multigeneration studies in the toxicological evaluation of six compounds, namely: a) a synthetic anabolic steroid with hormonal (antigonadotropic) activity, trenbolone acetate; b) a colouring additive with some cumulative toxicity, canthaxanthin; c) a lipophyllic drug with effects on neuron transmission, ivermectin; d) a teratogenic benzimidazole, albendazole; e) a genotoxic molecule, olaquindox; f) a drug with male reproductive toxicity, closantel. Finally, the endpoints evaluated in the multigeneration studies might be utilized also in field studies aimed at evaluating the long-term reproductive impact of chemicals in farm species. PMID- 1303034 TI - Veterinary primary health care in Italy. AB - The role of Veterinary Services in the field of primary health care according to the principles expressed by the World Health Organization is described. In more details, the contribution that Veterinary Services can give in Italy at local level to promote programmes of primary health care is considered, especially in the field of veterinary urban and rural hygiene, hygiene of food of animal origin and health education. PMID- 1303035 TI - Intersectoral collaboration in animal and human health. AB - A review is made of the health fields where collaboration between veterinarians and physicians and with other professions is most needed. The main obstacles encountered in this collaboration are recognized in institutional and attitudinal factors such as the type of administration in which veterinary services are located, economic interests, isolated spheres of activity of both veterinarians and physicians, reactions of the public to Veterinary Public Health action, insufficient fund allocation, etc. Control of echinococcosis/hydatidosis and brucellosis is given as an example of fruitful intersectoral collaboration supported by health institutions at local and international levels. It is stressed that the need for intersectoral collaboration is being increasingly and universally accepted with the active involvement of concerned organizations at all levels. PMID- 1303036 TI - The state of food hygiene and foodborne diseases: requirements for the future. AB - The current world situation of foodborne diseases is reviewed with an analysis of the factors responsible for their occurrence in both developed and developing countries. Strategies to solve the problems associated with food hygiene are also reviewed with special attention to the most recent approaches identified and worked out by the main institutions concerned. Specific suggestions are given for more effective planning and implementation of future global food hygiene programmes. PMID- 1303037 TI - Hazard analysis critical control point (HACCP) in public catering services: a modified method, combined to bacteriologic assay. AB - During 1990 and 1991 the Veterinary and Public Health Services of USL 35 of Ravenna carried out a research programme aimed at the control of food-borne diseases in the sector of public catering services, in collaboration with the Public Health Laboratory (Presidio Multizonale di Prevenzione). The objectives were: obtaining sure information about health hazards in public catering services; checking structural characteristics and equipment of workrooms in restaurants, hotels and refectories; verifying food preparation and preservation methods; promoting health education to increase employees' awareness of hygiene related problems. The first objective, evaluation of the level of the control of the workrooms exerted on the food contamination hazard by pathogenic or potentially pathogenic organisms, was carried out by allotting specific scores to several characteristics of laboratories or workers' habits, as suggested by the "Hazard Analysis Critical Control Point" (HACCP) method for butcher's shops and fish markets. Five hundred ninety-eight public catering service units have been inspected in restaurants, hotels, school-refectories, factories, hospitals and social houses; 2,097 bacteriological examinations by agar-contact plates and swabs were carried out; 118 preserved-food temperatures were measured, especially in deep-frozen and cooked food; 70 food specimens were tested to search for Salmonella spp. and Staphylococcus aureus and measure Total Aerobic Mesophilic Weight. The presence of Enterobacteriaceae and Escherichia coli was also tested. PMID- 1303038 TI - Animals as hosts of zoonoses. AB - The different aspects of the host/parasite relationships are taken into consideration along with the factors that can affect their behavioural patterns. Special attention has been given to the conditions which are involved in the development and establishment of the host/parasite association with an account of the various forms of this coexistence, such as proper parasitism, mutualism, commensalism and symbiosis. The rules which must be complied with to secure the survival of parasites and the perpetuation and completion of the parasitic life cycles are described. The special role of man as a host of zoonotic agents and the main approaches to zoonoses control are considered. PMID- 1303039 TI - Echinococcosis/hydatidosis: socio-economic consequences and economic analyses of control programmes. AB - A review is made of the socio-economic consequences of echinococcosis/hydatidosis and of the methods of economic analysis of control programmes. The main costs and benefits (both financial and social) which should be taken into consideration in evaluating health action are also examined. PMID- 1303040 TI - A study of factors influencing intestinal parasites in dogs. AB - Coprological examinations were made on 686 owned dogs (23% of the total number of the registered dogs) in a semiurban area of the province of Bologna including the small towns of S. Agata, S. Giovanni in Persiceto, Sala Bolognese and Crevalcore. The results of the coprological tests were evaluated in association with the data obtained from the owners about the origin and the use or function of the animals, veterinary assistance, diet, cohabitation with other dogs, and the presence of gastrointestinal conditions. Prevalence rates were 7.0% for ascarids, 3.6% for tapeworms, 7.1% for coccidia, 2.8% for hookworms, 28.6% for whipworms. On the whole, the animals positive for gastrointestinal parasites were 37.5% of those examined. Multiple linear regression analysis indicated that the presence of gastrointestinal parasites in general was influenced by the use of the animals, veterinary assistance, age, anthelminthic treatments and cohabitation with other dogs. The presence of ascarids appeared to be influenced by age and veterinary assistance; that of cestodes by veterinary assistance; that of coccidia by cohabitation with other dogs; that of whipworms by function, treatments, veterinary assistance and age. None of the variables considered in the analysis could explain the presence of hookworms. Factor analysis grouped the variables considered into 5 factors: the first was associated with veterinary assistance; the second with the animal's function and the presence of whipworms, hookworms and tapeworms; the third with cohabitation, origin and presence of coccidia; the fourth with the presence of fresh meat (cooked, raw or frozen) in the diet, age and positivity for ascarids; the fifth with sex and the presence of gastroenteric conditions. PMID- 1303041 TI - Evaluation of the size of stray dog population and of related problems in Emilia Romagna. AB - An investigation was carried out on the diffusion of stray dog populations in Emilia-Romagna by submitting a questionnaire/interview. 30 gamekeeper officers and 21 public veterinarians of Bologna and Forli provinces were interviewed. The data collected were compared with the official data of the Health Council of the Emilia-Romagna Region. Statistical analysis confirmed a correlation between number of biting dogs and inhabitants of the province; number of captured dogs and registered dogs; number of biting dogs and owned dogs, and the existence of factors favouring dog straying in mountain areas. PMID- 1303042 TI - Dog-transmitted zoonoses: a serological survey in the province of Bologna. AB - Eight hundred and two sera of owned dogs from four small towns north-west of Bologna were examined for the presence of antibodies against Coxiella burnetii and Leishmania infantum. At the same time, 149 sera of 69 dog owners from the same area were tested for the presence of antibodies to Q fever, leishmaniasis, echinococcosis/hydatidosis and toxocarosis. Of the 802 dog sera, 7 (0.87%) were positive for Q fever. Of the 69 dog owners, 24 (35%) were positive for Q fever, 4 (6%) for echinococcosis/hydatidosis and 3 (4%) for toxocarosis. Some epidemiological evaluations are made on the possible role played by the dog in spreading the zoonoses considered, at least in the area examined. PMID- 1303043 TI - Bovine spongiform encephalopathy: an overview. AB - Bovine spongiform encephalopathy (BSE), a novel disease of cattle first described in 1986, has now reached epidemic proportion in Great Britain with about 500 cases a week. The clinical, epidemiological, and pathological characteristics of BSE are described. Moreover, the etiopathogenetic mechanisms of spongiform encephalopathies are reviewed. Legislative measures to prevent the spread of BSE in Italy and in other EEC countries and to minimize the theoretical risk to man are reported. PMID- 1303044 TI - Intersectoral cooperation training: a tool for health personnel development. AB - The present paper describes some training experiences for improving intersectoral collaboration in the public health sector, between Medical and Veterinary personnel, working at the same level, local or regional, but in different preventive Services. It stresses that intersectoral collaboration is an important resource in public health planning and in developing health system as well as a real tool for health personnel development. PMID- 1303045 TI - The control of human brucellosis in the Campania region: an updating of knowledge and results obtained by the third year of the programme activities. AB - A control programme for brucellosis in Campania was started in 1988, in the province of Caserta, and implied different actions at the regional and provincial levels. The section of the work described here regards the updating of the results obtained during the third year of the project activity. The action performed included experimentation of data sheets in the province of Caserta to gain information on the factors conditioning brucellosis, gathering and analysis of ISTAT data on the size of livestock population as an actual or potential source of infection for man, epidemiological surveillance of human cases, census of dairies, and public health measures taken by the Regional Council. The results show that improvement of human brucellosis surveillance is in progress, whereas the programme implementation has provided a clearer picture of the situation with better understanding of the factors affecting the disease occurrence. Such problems posed by the project management as difficult maintenance of sufficient collaboration between veterinarians and physicians, scarce participation of local and regional administrations, resistance opposed by some categories, and reduced availability of financial resources are also discussed. PMID- 1303046 TI - Mortality rates among psychiatric patients, during and after the "psychiatric reform", in the area of Rome (Italy). AB - The issue of supposedly high mortality rates among psychiatric patients discharged from mental hospitals after the implementation in Italy of Law 180 is controversial. We have studied a cohort of 1858 long-term psychiatric inpatients of Public Mental Hospitals in the area of Rome (Italy), followed up for 9 years during and after the implementation of Law 180. As expected, age adjusted mortality rates were higher than those observed in the general population living in the study area, and death rates among patients with "organic mental disorders" were higher than those among patients with "functional disorders". No difference in death rates was observed between the group of discharged patients and that of patients not yet discharged. PMID- 1303047 TI - [Anopheles in Italy: distribution on rice lands in the provinces of Grosseto and Siena]. AB - The Laboratory of Parasitology of Istituto Superiore di Sanita acts as a coordinating centre for anophelism data collection in Italy, and collaborates with the health local authorities. This specific investigation takes into consideration several areas in the provinces of Grosseto and Siena, focusing attention on the rice fields, which are today the most important anopheline breeding sites in Maremma. The records collected in collaboration with the Department of Environmental Zoology (USL 28 Grosseto), show a high density of A. labranchiae, the potential malaria vector, in the coastal areas of Grosseto province, and a decreased susceptibility to some insecticides. Among the other anopheline species found, only A. atroparvus (the species most present on the inland hills of the provinces of Grosseto and Siena) show a remarkable density. PMID- 1303048 TI - [National Register of congenital hypothyroidism]. AB - The results of five years activity of the National Register of children with Congenital Hypothyroidism (NRCH) have been evaluated. NRCH was established in Italy in 1987, as a pilot project of Health Ministry. All Italian Centers in charge of the screening, treatment and follow-up of CH are involved in the program. The results have provided further epidemiological informations about CH in Italy and have evidenced some aspects in the screening organization which had to be improved. Discussion of Register data in annual meetings has recently allowed to obtain an improvement especially for the beginning of treatment and the used dose of therapy. PMID- 1303049 TI - Prevalence of mental disorders in Tuscany: a community study in Lari (Pisa). AB - A number of population studies of mental disorders has been carried out using standardized diagnostic tools. We performed a study of this type in the small town of Lari (Pisa) with the objectives of estimating the prevalence of mental disorders, including "minor" disorders, and of comparing our estimates with similar studies carried out in UK and Greece using identical methods (PSE-IX and CATEGO). The prevalence of individuals with mental disorders in our study population was 15.4% similar to that observed in Greece (16%) and higher than that observed in London (10%). Prevalence of "obsessive neurosis" was higher in London as compared to Lari and Athens, while the opposite was true for "generalized anxiety". PMID- 1303050 TI - [Somatomedins/insulin-like growth factors (IGFs): chemical and functional characteristics]. AB - The insulin-like growth factors constitute a family of peptides which have structural homology with proinsulin, and which possess broad anabolic and mitogenic action in wide variety of tissues. The two main forms of IGFs in serum of adults are insulin-like growth factor I (IGFI) and insulin-like growth factor II (IGFII). IGFI appears to be the major growth factor involved in postnatal growth and is believed to mediate most (if not all) of the growth promoting effects of growth hormone (GH). IGFII may be involved in embryonic and fetal growth. It is the aim of this article to present an account of recent advances in the understanding of the origins, functions, and clinical significance of these peptides. Particularly the role of IGFs in fetal growth during normal and diabetic pregnancies. PMID- 1303051 TI - [Immunogenicity of a recombinant vaccine against viral hepatitis B]. AB - The introduction in Italy of recombinant DNA hepatitis B vaccines has allowed to plan out a very important programme of vaccination; in Italy the compulsory vaccination against hepatitis B virus begun from 1991. Because of the reduction of vaccine cost, the screening for serum markers of HBV infection is needless. On the contrary, the test of antiHBs titres after the vaccination is important in order to take into account a booster vaccine dose and to carry out revaccination strategies. In this study, we analyzed 419 subjects vaccinated with Engerix-B; the immune response was correlated with private and behaviour data. PMID- 1303052 TI - [Evaluation of work styles using the clinical case method at the departments of mental health in the region of Campania]. AB - In the present study, designed after the Australian "Quality Assurance Project", the same 9 clinical "vignettes" relative to 3 schizophrenia cases, 3 depressives and 3 neurosis were read by 48 psychiatrists of the Campania Region (Italy). For each case, the psychiatrists were requested to give their opinions on best place of treatment, psycoactive drugs, psychotherapy, etc. A remarkable variability among psychiatrists was observed, regarding not only psycotherapy but drug therapy as well. PMID- 1303053 TI - [Models and strategies for the control of air pollution in large urban areas]. AB - In the attempt to define the characteristics of a global approach to the problem of atmospheric pollution, the mathematical and statisticals tools currently available are presented which will allow the rationalization of both the study and the management of reduction policy. An example of a possible application of this approach is given, which presents the results obtained by modelling the data on "conventional" pollutants furnished by the experimental sampling station set up at the Istituto Superiore di Sanita (ISS) in Rome. Since the suggested approach may not do without an integrated management of date, a hypothesis for an information system is outlined as well. PMID- 1303054 TI - [Territorial distribution of mortality from malignant tumors of the pleura in Italy]. AB - Mortality from malignant pleural neoplasms in Italy, 1980-87, was studied in order to detect areas at risk. The number of observed deaths occurring in each of the 8000 Italian municipalities was contrasted to the expected figure obtained from regional and/or national rates; whenever a significant increase, based on at least three observed cases, was detected, the municipality was included in the study. The main findings in Piedmont concern the city of Casale Monferrato, where an important asbestos cement factory is located, and some areas characterized by the presence of the textile industry. Genoa and other harbours of the northwestern coast, where important shipyards are located, were detected. In Lombardy an increased in risk concerning women was observed in several municipalities. Major increases in risk were seen in Venice. Trieste and Monfalcone, where important shipyards are located. In Tuscany, the highest risk was reported in Leghorn and surrounding areas; naval industry and chemical industries should be considered. In southern Italy, several cities with industrial harbours were shown to be at risk. PMID- 1303055 TI - [Hemangioma of the petrous bone. Diagnosis and treatment]. AB - Hemangiomas of the temporal bone are benign, vascular and are tumors. The diagnosis is in most cases made during the operation because the symptoms are non conclusive. Two cases were recently observed: one simulating a Meniere disease while the tumor was developed close to the jugular bulb and the endolymphatic sac; the second invaded the geniculate area and the petrous apex and was revealed by a progressive facial palsy. PMID- 1303056 TI - [Calcifying epithelial odontogenic tumor or Pindborg tumor. Apropos of a case]. PMID- 1303057 TI - [Neuroendocrine giant-cell epithelioma. Description of a clinical case and review of the literature]. AB - Neuroendocrine tumors are rare neoplasms of the larynx and hypopharynx. This tumors are divided in paragangliomas (usually benign, although malignant case have been reported), large cell neuroendocrine carcinoma, described in this case as a primary pharyngo-laryngeal locate, and small cell neuroendocrine carcinoma (characterized by early and diffuse metastatic disease, and best treated by radiotherapy and chemotherapy). Through the international literature, the authors reviewed the characteristics of the large cell neuroendocrine tumors and their management. PMID- 1303058 TI - [Anatomical limits of endonasal ethmoidectomy]. AB - Constant anatomic boundaries of the lateral mass of the ethnoid are described, based on data from microdissections, endoscopic examinations, computed tomography imaging and histology in 12 subjects. As with surgical progression, identification of these boundaries follows the lateral orbital and superior craniofrontal surfaces. The "starred groove formation", ethmoidal roof lamina and ethmoidosphenoidal recesses are the safety beacons for endonasal ethmoidectomy under endoscopic control. PMID- 1303059 TI - [Asthma and polyposis. Efficacy and adverse effect of endonasal ethmoidectomy. Results apropos of 70 patients]. AB - The authors report the efficacy and adverse effects of intranasal ethmoidectomy in 70 patients with asthma and persistent severe symptoms from nasosinal polyposis despite repeated prior treatment. The efficacy was defined according to the evolution of symptoms and endoscopic findings. Adverse effects were evaluated according to subjective clinical and therapeutic data in all 70 patients. In addition, 25 patients had complete pre and post-operative pulmonary function tests. The results confirm that intranasal micro-surgery does not increase the severity of asthma. On the other hand, no significant improvement in bronchial function was noted after ethmoidectomy. Finally, the authors emphasize the poorer results obtained in Widal's disease and the importance, after the failure of medical treatment, of using of sufficiently extensive surgical procedure in order to decrease the incidence of recurrences. PMID- 1303060 TI - [Is facial nerve visible on magnetic resonance imaging?]. AB - The internal architecture of the parotid gland was studied by nuclear magnetic resonance (NMR) imaging, particular attention being paid to the intra-parotid portion of the facial nerve. Currently available apparatuses provide high resolution images of previously poorly elucidated anatomic details. Certain authors consider that images in the axial plane in T1 allow direct visualization of the facial nerve and its branches in the form of low frequency linear signals within the gland. The present study, based on radio-anatomic correlations and date determined in a healthy volunteer, demonstrated that these structures correspond in fact to segments of the excretory canal tree, the facial nerve and its branches being invisible on NMR imaging. It is not possible, therefore, to determine the location of a parotid tumor in relation to these nerve elements using this imaging technique. PMID- 1303061 TI - [Septic erosion of the internal carotid artery and retrostylian phlegmon. Apropos of a case]. AB - The vascular complications of peritonsillar phlegmons have become exceptional. On the basis of a recent case, the authors sum up the criteria of severity, including: white puncture sample, paralysis of the 9th, 10th, 11th, 12th cranial nerves and of the cervical sympathetic nerve. Computed tomography allows not only refining the topographic diagnosis, but even sometimes diagnosing a pseudoaneurysm before it is fissured. At this stage, intraoperative radiology may probably prevent the unavoidable secondary rupture. If it cannot be used, preventive ligation must be proposed. In the absence of cataclysmic hemorrhage, this easier procedure usually does not cause any irreversible neurological deficit. If performed in emergency, it may entail a major risk, not only a neurological risk, but a vital risk as well. PMID- 1303062 TI - [Vocals in silence and noise. A simple test of resistance of intelligibility in noisy environment]. AB - We have all noticed that there was no coincidence between the conventional audiometric tests--tonal, vocal, Metz tests--and the degree of impairment of understandability in noisy environments that the patients report. Some of them handle this problem better than these conventional tests suggest, others less well. The aim of this study is to take account of this dominating functional complaint: impairment in noisy conditions, and to assess it in order to follow up its evolution after medical, surgical and prosthetic treatments. The aim of the authors has been to describe an easy examination to be implemented in any ENT surgery fitted with a free-field vocal testing equipment. The results show that this test cas differentiate between "noise-resistant" subjects and those that do not "resist" well. The discussion defines the limitations of this test, which are due to its deliberate simplicity, and the caution required for its psychoacoustic and physiological interpretation. The conclusion confirms its merits, since it can discriminate and help choose more accurate tests--temporal tests, frequency selectiveness charts, twin-ear tests, cognitive AEP. PMID- 1303063 TI - Determination of urinary glucose by a flow injection analysis amperometric biosensor and ion-exchange chromatography. AB - A practical biosensor system has been developed for the determination of urinary glucose using a flow-injection analysis (FIA) amperometric detector and ion exchange chromatography. Glucose oxidase was immobilized onto porous aminopropyl glass beads via glutaraldehyde activation to form an immobilized enzyme column. On the basis of its negative charge at pH 5.5, endogenous urate in urine samples was effectively retained by an upstream anion-exchange resin column. The biosensor system possessed a sensitivity of 160 +/- 2.4 RU microM-1 (RU or relative unit is defined as 2.86 microV at the detection output) for glucose with a minimum detection level of 10 microM. When applied for the determination of urinary glucose, the result obtained compared very well with that of the widely accepted hexokinase assay. The immobilized glucose oxidase could be reused for more than 1000 repeated analyses without losing its original activity. The reuse of the acetate anion-exchange column before replacement would be about 25-30 analyses. Acetaminophen and ascorbic acid were also effectively adsorbed by the acetate anion exchanger. The introduction of this type of anion exchanger thus greatly improved the selectivity of the FIA biosensor system and fostered its applicability for the determination of glucose in urine samples. PMID- 1303064 TI - Glucose biosensor using glucose oxidase immobilized in polyaniline. AB - A biosensor for glucose utilizing kinetics of glucose oxidase (EC 1.1.3.4.) was developed. The enzyme was immobilized on polyaniline by covalent bonding, using glutaraldehyde as a bifunctional agent. The system showed a linear response up to 2.2 mM of glucose with a response time of 2.5-4.0 min. In addition, the immobilized enzyme had a higher activity between pH 6.5 and 7.5. The system retained 50% of its activity after 30 d of daily use. The optical absorption spectra of the polyaniline/glucose oxidase electrode after glucose had been added to the buffer solution showed that the absorption band around 800 nm had changed considerably when glucose was allowed to react with the electrode. This optical variation makes polyaniline a very promising polymer for use as a support in optical sensor for clinical application. PMID- 1303065 TI - Purification and characterization of a milk clotting protease from Mucor bacilliformis. AB - An acid protease having milk clotting activity has been isolated from Mucor bacilliformis cultures. The enzyme was basically purified by ionic exchange chromatography. An average yield of 29 mg purified product was obtained from 100 mL crude extract. As purity criteria, SDS-PAGE, reverse-phase HPLC, and N terminal analysis were performed. The protease is a protein composed of a single polypeptide chain with glycine at the N-terminus. The mol wt is approx 32,000, and its amino acid composition is very similar to those of other fungal proteases. As expected, its clotting activity was drastically inhibited by pepstatin A action. On the other hand, its instability against heat treatment and its clotting/proteolytic activity ratio indicate that it may be considered as a potential substitute for bovine chymosin. PMID- 1303066 TI - Ultrastructural modifications of patellar tendon fibres used as anterior cruciate ligament (ACL) replacement. AB - Using transmission electron microscopy, patellar tendons that had been autografted to replace the ACL were studied. Follow-up biopsies, performed at 6, 12 and 24 months after reconstructive surgery demonstrated that the autograft patellar tendons had undergone considerable change. After 6 months, the large collagen fibrils were less numerous and more widely spaced. The spaces were occupied by dense colonies of very small, newly-formed collagen fibrils and were rich in glycosaminoglycans. Small elastic fibres, fibrocytes, round cells with abundant rough endoplasmic reticulum and macrophage-like cells were scattered among the collagen fibrils. At 12 months, sporadic clumps of large collagen fibrils were seen between the compact bundles of small, uniform collagen fibrils. Both elastic and oxytalan fibres were observed; round cells with abundant rough endoplasmic reticulum were the most prevalent cell type. At 24 months, the tissue had the appearance of a normal ligament. The small uniform collagen fibrils had formed large, compact bundles that were prevalently arrayed parallel to the long axis. Both elastic and oxytalan fibres were observed and the numerous cells present exhibited the same morphological features as those observed at 12 months after surgery. The appearance of compact collagen bundles, the abundant elastic system and the abundance of active cells observed in the patellar tendon autograft 24 months after implantation, suggest that this type of tissue is a valid functional ACL substitute of a knee required to perform normal mechanical activity. PMID- 1303067 TI - Morphologic study of the gastric mucosa during Helicobacter pylori infections. AB - The purpose of the present, study was to underline the importance of the use of SEM in the evaluation of Helicobacter pylori (HP) - Induced gastritis. Gastric biopsies from eleven patients affected by HP infections were examined using Light Microscope (LM), Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM). SEM allowed for the localization of even small groups of bacteria and to demonstrate the many morphologic changes due to the infective phlogosis. The signs of cellular suffering and the relationship between bacteria and microvilli are of particular interest. PMID- 1303068 TI - Ultrastructural observations on blood vessels surrounding normal and regenerating spinal cord in newt. AB - The ultrastructural analysis of capillaries surrounding normal and regenerating caudal spinal cords of two species of newt (Triturus vulgaris and T. cristatus) is reported. Around normal spinal cords, capillaries were generally continuous. Surrounding the regenerating spinal cords the various capillaries of the regenerating blastema appeared discontinuous with small or broad gaps along the capillary wall. This was seen even after two months of tail regeneration when the spinal cord was similar to the normal and many axons were myelinating. These morphological findings suggest that during tail regeneration in newts the blood brain barrier is not very effective. Also extravasating mature and immature blood cells were observed inside regenerating capillaries. Therefore growing capillaries can exchange metabolites and, possibly, growth factors with the nervous tissue and the other regenerating tissues. PMID- 1303069 TI - Pancreatic arteries and anatomicosurgical segments in dogs. AB - The distribution of the arteries supplying the pancreas was studied in 22 adult dogs (7 females and 15 males) of mixed breed. The pancreas was divided into 2 lobes, 4 sectors and 6 anatomicosurgical segments. These segments are defined as territories recognizable anatomically and surgically removable. The division and subdivision of the pancreas and the segmental arteries were the following: Left Lobe: Omental sector: I. Proximal segment: splenic a. II. Middle segment: splenic a. III. Distal segment: gastroduodenal and right gastro-omental Interpapillary sector: IV. Juxtaduodenal segment: cranial pancreaticoduodenal a. Right Lobe: Distal sector: V. Distal segment: cranial pancreaticoduodenal a. Proximal sector: VI. Proximal segment: caudal pancreaticoduodenal a. PMID- 1303070 TI - Recurrent cutaneous erythralgia and arthralgia. AB - Two cases are reported of Vietnamese men who presented in young adult life with recurrent, painful, erythematous patches (which we have termed "erythralgia") over and adjacent to joints and accompanied by marked constitutional symptoms of malaise and lethargy, arthralgia and in one patient, fever. In the other, from the onset of the disease there were nodules over the bony prominences and in the interphalangeal regions of the fingers. The duration of the disease was over 12 years, the duration of each episode without therapy was one week and the interval between episodes was one to two weeks. In addition the patients showed a raised ESR and peripheral neutrophil leucocytosis of over 70%. There was a rapid response, within hours, to non-steroidal anti-inflammatory agents. Skin biopsies taken at varying stages of the disease episode failed to demonstrate neutrophils thereby failing to satisfy one major criterion of Sweet's Syndrome. Direct immunofluorescence studies were negative. Biopsy of the nodules did not show rheumatoid pathology. The serum rheumatoid factor was negative. Investigations failed to demonstrate any recognised pattern of cutaneous or rheumatologic disease; infections such as borreliosis were excluded. Both patients showed evidence of past hepatitis B infection. As recurrent painful cutaneous erythema is an uncommon phenomenon in dermatology except where the patient is suffering from recurrent cellulitis of the lower limbs, the patients reported here exhibit a pattern of disease not previously described. PMID- 1303071 TI - Review of Fifth International Psoriasis Symposium. San Francisco, July 1991. PMID- 1303072 TI - A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne. AB - Alpha hydroxy acids (AHA's) or "fruit acids" are a special group of organic acids found in many natural foods. They have been described in the literature for the treatment of a number of conditions in which abnormal keratinization consistently contributes to pathogenesis. These include the icthyoses, warts, psoriasis, eczema and acne. We have performed a double-blind clinical trial on 150 patients to evaluate the efficacy and skin tolerance of the alpha hydroxy acid gluconolactone 14% in solution (Nuvoderm lotion) in the treatment of mild to moderate acne when compared with its vehicle (placebo) and 5% benzoyl peroxide lotion. The results of this study showed that both gluconolactone and benzoyl peroxide had a significant effect in improving patients' acne by reducing the number of lesions (inflamed and non-inflamed). Furthermore, fewer side-effects were experienced by patients treated with gluconolactone when compared with benzoyl peroxide. PMID- 1303073 TI - Congenital inclusion dermoid cysts of the scalp. AB - The natural history of congenital inclusion dermoid cysts of the scalp is unknown. We report three cases of this condition, which has been followed from birth for up to ten years. Dermoids are congenital subcutaneous cysts, which gradually flatten and scar over a number of years. The lesions are covered with skin showing focal alopecia but they may be surrounded by a collar of hypertropic hair. Later in life flattened cysts may be mistaken for aplasia cutis, but the history of a cyst at birth allows the clinician to distinguish these two conditions. As these cysts have a potential for intracranial extension, this is an important clinical entity. PMID- 1303074 TI - Subcutaneous fat necrosis of the newborn complicated by hypercalcaemia and thrombocytopenia. AB - Subcutaneous fat necrosis of the newborn is an uncommon but distinctive condition which appears in the first six weeks of life, associated with variable degrees of hypercalcaemia and which resolves spontaneously over months. We report a case of subcutaneous fat necrosis of the newborn following perinatal distress and complicated by thrombocytopenia and hypercalcaemia. PMID- 1303075 TI - Tea tree oil in the treatment of tinea pedis. AB - Tea tree oil (an essential oil derived primarily from the Australian native Melaleuca alternifolia) has been used as a topical antiseptic agent since the early part of this century for a wide variety of skin infections; however, to date, the evidence for its efficacy in fungal infections is still largely anecdotal. One hundred and four patients completed a randomized, double-blind trial to evaluate the efficacy of 10% w/w tea tree oil cream compared with 1% tolnaftate and placebo creams in the treatment of tinea pedis. Significantly more tolnaftate-treated patients (85%) than tea tree oil (30%) and placebo-treated patients (21%) showed conversion to negative culture at the end of therapy (p < 0.001); there was no statistically significant difference between tea tree oil and placebo groups. All three groups demonstrated improvement in clinical condition based on the four clinical parameters of scaling, inflammation, itching and burning. The tea tree oil group (24/37) and the tolnaftate group (19/33) showed significant improvement in clinical condition when compared to the placebo group (14/34; p = 0.022 and p = 0.018 respectively). Tea tree oil cream (10% w/w) appears to reduce the symptomatology of tinea pedis as effectively as tolnaftate 1% but is no more effective than placebo in achieving a mycological cure. This may be the basis for the popular use of tea tree oil in the treatment of tinea pedis. PMID- 1303076 TI - Linear scleroderma with severe leg deformity. AB - Linear scleroderma is an unusual form of localised scleroderma, mainly affecting the legs and occurring primarily in children. Sometimes the linear lesions may extend to involve the underlying muscles and bones, with severe disturbances in growth and possibly flexion deformities of the legs. In this study, two cases suffering from linear scleroderma of the legs are presented. PMID- 1303077 TI - Dermatophyte and non-dermatophyte onychomycosis in Singapore. AB - Onychomycosis is caused by dermatophytes, moulds and yeasts. It is important to identify the non-dermatophyte moulds as they are resistant to the usual anti fungals. A prospective study was undertaken in the National Skin Centre, Singapore to study the pattern of dermatophyte and non-dermatophyte onychomycosis. 53 male and 47 female patients seen between June 1990 and June 1991 were entered into the study. Direct microscopy was done and the nail clippings were cultured. Toe and finger nails were equally infected. Dermatophytes were isolated from 21 patients namely, T. rubrum (12/21), T. interdigitale (5/21), T. mentagrophytes (3/21) and T. violaceum (1/21). Candida onychomycosis occurred in 39 patients and was caused by C. albicans (38/39) and C. parapsilosis (1/39). 37/39 patients had associated paronychia. 5 types of moulds were isolated from 12 patients, namely Fusarium species (6/12), Aspergillus species (3/12), S. brevicaulis (1/12), Aureobasilium species (1/12) and Penicillium species (1/12). Although the clinical pattern and microscopy may predict the type of organisms, in practice this is difficult. Only cultures were confirmatory. 28% (28/100) had negative cultures despite a positive microscopy, and moulds (12/100) grown might be contaminants rather than pathogens. PMID- 1303078 TI - Scytalidium hyalinum isolated from the toe nail of an Australian patient. AB - The isolation of Scytalidium hyalinum from the toe nail of a patient from Melbourne is reported. This is the first record of the isolation of this fungus from a clinical site in Australia. A brief history is given of the occurrence of Scytalidium hyalinum and the related fungus, Hendersonula toruloidea, in tinea pedis and tinea unguium in immigrants to the United Kingdom from tropical countries. Attention is drawn to the possible presence of these dermatophyte-like infections in patients in Australia. PMID- 1303079 TI - Four non-endemic New Zealand cases of chromoblastomycosis. AB - The majority of cases of chromoblastomycosis are reported from tropical to subtropical countries; only one previous case being reported from New Zealand. Four non-endemic cases in Pacific Island patients are described. All of the New Zealand cases were caused by Fonsecaea pedrosoi. In the present report, one patient was successfully treated by excision of the lesion followed by skin grafting. Another was treated with 200 mg ketoconazole daily for 10 weeks with no obvious improvement. No follow-up on the treatment of this case nor of the remaining two patients is available. This disease must be included in the differential diagnosis in patients who present with chronic lesions affecting the skin and subcutaneous tissues. PMID- 1303080 TI - A review of the 1992 annual meeting of the British Society for Investigative Dermatology. PMID- 1303081 TI - Australian Dermatopathology Society. Digital dilemma. PMID- 1303082 TI - Incidence of Aeromonas isolated from diarrhoeal children and study of some virulence factors in the isolates. AB - Stool samples from 305 children with diarrhoea and equal number of age and sex matched non-diarrhoeal control children, less than 5 years of age, were examined during the period from Sept 1988 to April 1989. Aeromonas spp. were isolated from 37 (12.1%) diarrhoeal and 05 (1.6%) control cases. Out of 37 diarrhoeal isolates 13 (35.1%) were A. hydrophila, 19 (51.1%) A. sobria and 05 (13.5%) A. caviae. All the isolated strains were tested for haem agglutination property and haemolysin production. Seventeen diarrhoeal and 05 control isolates were tested for cytotoxin production in He La cell line and enterotoxin production in rat ileal loop model and suckling mouse model. Chinese hamster ovary cell (CHO) assay and Gm-1 ELISA methods were also employed. Cytotoxin production was found in 82.5% of diarrhoeal and 40% of control isolates. Haemagglutination was found in 62.1% of Aeromonas isolated from diarrhoeal children and 20% from control children. Enterotoxin production was detected in 58.8% diarrhoeal and none of the control isolates by either of the methods. Of the virulence factors enterotoxin production was found to correlate well with enteropathogenicity but haemolysin, cytotoxin and haemagglutinin did not. PMID- 1303083 TI - Role of radioiodine in management of thyroid cancer: experience with 70 cases. AB - Results of 70 cases of differentiated thyroid carcinoma managed with I131 and surgery have been reported. These results add to the body of knowledge that already exists in the field of treatment of thyroid cancer with radioactive iodine. These results also indicate that the success of radioiodine therapy depends on adequate surgical removal of the thyroid tissue. PMID- 1303084 TI - Utilization of health care facilities in Bangladesh. AB - This study was conducted among 310 families at some urban and rural areas of Mymensingh district to know the pattern of utilization of available health care facilities by them. Out of 310 families, 150 were from 4 villages of Muktagacha thana (rural) and 160 were from Mymensingh pouroshava (urban). It was observed that 93.3 percent from rural and 95.6 percent of urban population were utilizing modern health care facilities. Of them 40.6 percent from urban and 33.3 per cent of rural areas were found to prefer private sector facilities. More than three fourth of the urban children and half of the rural children of the families under study were found immunized. About 70 per cent of the town dwellers were availing MCH care. On the contrary the rate of utilization of MCH services by the village people was only 37.3 per cent. PMID- 1303085 TI - Indirect fluorescent antibody test in the serodiagnosis of visceral leishmaniasis in Bangladesh. AB - Indirect fluorescent antibody test (IFAT) was found to be 100% sensitive and 100% specific when tested with sera from 125 parasitologically proven kala-azar patients, 100 healthy controls and 50 sick control cases. Promastigotes of both L. enriettii and L. donovani as well as amastigotes of L. enriettii were found equally satisfactory as antigen for IFAT. From the results of the present study, it is concluded that IFAT is a highly sensitive as well as specific serological test for the diagnosis of kala-azar. PMID- 1303086 TI - A psycho-social study on genito-urinary fistula. AB - This study was done on a series of 132 vesico-vaginal fistula (V.V.F.) cases to assess the social factors that are related to this morbidity and its psycho social effects on them. About 54% of the respondents developed VVF as an outcome of their first pregnancy and none of them had a living child. Of this 39% were in the age group of 15-20 years. About 68% were illiterate and 22% had received formal education for up to 5 years. Fifty two per cent of the subjects had a family income of up to Tk. 1,000 only per month. Almost all were Muslims (94.7%). Of the respondents 64.6% had home delivery by TBA and 72% had history of prolonged labour. Fifty six per cent of the subjects did not like to avail the health facilities of the nearby clinic/hospital. Lack of privacy, objection from husband/family and conduction of delivery by male doctor were mentioned as causes for not availing the facilities by this large group. Indifferent attitude of husband and in-laws, expressed willingness of husband for taking another wife, disturbed socio-psycho-sexual life and deterioration of general health were the after effects of the morbidity at individual, conjugal and community level of the respondents. PMID- 1303087 TI - Rhesus genotype frequency in Bangladeshi population. AB - The prevalence of Rhesus genotypes in Bangladesh has been studied and several important findings were observed. This being the initial report, includes a population of 1600 only. By using five Rh antisera (Anti-C, Anti-D, Anti-E, Anti c and Anti-e) a genotype can be deduced since anti-d is not available. More often only a probable genotype can be suggested after reference to the known chromosome frequencies in the population. By using family studies in conjunction, it may be possible to determine genotype with certainty. The prominent Rhesus genotype was CDe/cDE (R1R2), i.e., 39.75%, Rhesus genotype cde/cde (rr) was found to be only 1.75%. The genotype cdE/cde (r"r) was not detected in the present series of Bangladeshi population. These results have been compared with the English and the Indian Bengalee Hindu Population. PMID- 1303088 TI - The shortage of organs for transplantation. PMID- 1303089 TI - Reproducibility and validity of laser flare/cell meter measurements as an objective method of assessing intraocular inflammation. AB - Preoperative and postoperative anterior chamber reactions in a series of patients who had undergone cataract surgery were measured with a laser flare/cell meter (Kowa FC-1000, Kowa Instrument Corp, Japan) by two different technicians (A.M. and T.M.M.), and clinical assessments of inflammation were recorded. The average cell and flare readings of the two technicians were nearly identical at every time point, showing the laser flare/cell measurements to be highly reproducible. The correlations between laser flare/cell measurements and clinical assessments at postoperative time points were all highly positive (P less than .01), demonstrating the validity of the laser flare/cell measurements. PMID- 1303090 TI - A conversation with Dr. Jack Hinterman, our candidate for ADA president. Interview by Dr. Charles Owens. PMID- 1303091 TI - The T cell receptor gene and its association with human diseases. AB - The genetic organization and protein structure of the T cell receptor (TCR)/CD3 complex are currently under investigation, and recent work has provided information about its assembly, expression and function. This article reviews what is currently known about the structure and assembly of the TCR/CD3 complex. The TCR chains are members of the immunoglobulin gene superfamily and are generated by combinatorial associations of V, J, D, and C genes. The presence of certain gene rearrangements within these chains has been associated with lymphoproliferative disorders, autoimmune disease and immunodeficiencies. TCR rearrangements can be useful in the diagnosis of lymphoproliferative disorders and in the identification of patients who will subsequently relapse, once in remission. With respect to autoimmune disease, the possibility now exists of immunotherapy with TCR designer polypeptides to prevent disease. In patients with primary immunodeficiencies secondary to defects in expression of the TCR, the possibility of somatic gene therapy now exists. As more information unfolds about the role that TCR gene rearrangements have in various diseases, new insights are gained into better diagnosis and treatment. PMID- 1303092 TI - Altered expression of blood group A and H antigens on red cells from an acute leukemic patient. AB - Alternate expressions of the blood group A and H antigens on red cells are described in a patient with acute myelocytic leukemia. The patient's red cells showed mixed field agglutination with anti-A and anti-H sera and lectins, and no agglutination with anti-B serum. The agglutinability of the A red cells with Dolichos biflorus lectin was between A1 and A2 (A intermediate). Inagglutinable red cells were separated with anti-A agglutinin, and the proportion was about 80% of total cells. The agglutinating activity with Ulex europaeus anti-H of red cells, which were inagglutinable with anti-A, was 16 times weaker than that of group O cells. The weaker reaction with Ricinus communis lectin and the stronger reaction with Psathyrella velutina lectin on the inagglutinable cells with anti-A than those on the group O cells suggest that fucosyl alpha (1-2) and galactosyl beta (1-4) residues at the nonreducing end of carbohydrate chains of H antigens on the red cells were diminished, and N-acetylglucosaminyl beta (1-3) residues were sequentially exposed. His saliva contained A and H substances in normal amounts of a secretor. Serum alpha-N-acetylgalactosaminyltransferase activity which converts O red cells to A red cells was the same as those in sera from A1 individuals. These results suggest that the synthesis of H precursors is partially blocked in this patient's red cells. PMID- 1303093 TI - Genetic polymorphism of IgG in the mink. IX. High proportion of allotype producing lymphocytes in individuals with minor level of allotypes H3 and H4 in serum. AB - The levels of mink C gamma-allotypes (H3, H4, H6 and H8) were determined in sera, and the proportion of the corresponding allotype-synthesizing B cells was estimated in peripheral blood, spleen and mesenteric lymph nodes. Individual differences in H6 levels and, possibly, those in H8 were entirely dependent on the proliferation degree of the corresponding clone of B cells and also determined by the dosage of the structural gene. There was no correspondence between the great numbers of H3+, H4+ cells and low levels of H3 and H4 allotypes in the sera of the majority of minks with their minor expression. A possible cause of this discrepancy may be a blockade of the secretion of IgG by H3+, H4+ cells. There exists most likely a gene (or genes) controlling the blockade of IgG secretion. The regulation of C gamma-allotype expression is presumably effected in a manner specific to each of the allotypes. PMID- 1303094 TI - HLA-A region in highly sensitized patients: another immune response gene region. AB - HLA haplotypes were assigned by family typing in 94 prospective kidney transplant recipients. An HLA-A region of the HLA-A, B, DR haplotypes was found in association with high levels of antibodies against lymphocytes. There was a significant difference in the frequency of HLA-B8-positive haplotypes among the patients with regard to the distribution of HLA-A alleles (p = 0.0028); on the same haplotype the A1 and B8 alleles were found in moderately and weakly sensitized patients and HLA-A alleles other than A1 were present with B8 in highly sensitized patients. A significantly higher number of highly sensitized patients when compared with moderately sensitized patients had haplotypes with HLA-A alleles in negative linkage disequilibrium with HLA-B alleles (77 vs. 10%, p = 0.014). The results are in good agreement with a previous suggestion that the interaction between the HLA-A class I and class II regions regulates the immune response. Determination of HLA haplotypes might identify patients at high risk for broad and persisting sensitization. PMID- 1303095 TI - Group-specific component is not only a vitamin-D-binding protein. AB - The vitamin-D-binding protein (DBP), also called group-specific component, is well known for two main reasons: its genetic polymorphism, and its binding affinities for actin and vitamin D compounds. In recent years, additional binding affinities have been described for this puzzling molecule, without any significant biological explanations being given for these observations. The molecular genetic data for DBP are analyzed in order to show that the affinities for vitamin D are supported by the genetic variability. The molecular evolution of the protein shows that the ancestral gene was present long before the development of related genes, such as those for albumin and alpha-fetoprotein. Other affinities for actin, C5a-desArg and for a B lymphocyte mitogen are also discussed. DBP is mainly present in the circulating blood as an apoprotein. The cytoplasmic presence of DBP has not been confirmed, and the major question today is to understand the biological role of this protein. In the last part of the review, the discussion focuses on relating the different binding affinities of DBP to its biological activities. Avenues for future research are also outlined: these include DBP metabolism, the differentiation of macrophages, and the activity of DBP during embryonic development. PMID- 1303096 TI - Macrophages capable of inducing anterior chamber associated immune deviation demonstrate spleen-seeking migratory properties. AB - Antigens injected into the anterior chamber of the eye generate a deviant immune response (Anterior Chamber Associated Immune Deviation--ACAID) characterized by impaired delayed hypersensitivity and lack of complement-fixing antibodies. Both the antigen-containing eye and an intact spleen are required for ACAID induction. The eye's contribution takes the form of an antigen-specific, ACAID-inducing signal associated with blood-borne F4/80+ macrophages. Macrophages capable of carrying an ACAID-inducing signal can be harvested directly from the iris and ciliary body, or can be created by exposing F4/80+ peritoneal exudate cells to aqueous humor or to supernatants of cultured iris and ciliary body cells. In the present study, F4/80-bearing macrophages from the peritoneal cavity were exposed in vitro to supernatants of cultured iris and ciliary body cells and then labelled with PKH-2 prior to intravenous infusion into naive, syngeneic recipients. The pattern of distribution of these cells in spleen, lymph nodes, and blood was compared with similarly labeled cells exposed in vitro to medium alone. The results reveal that, compared to conventional peritoneal exudate cells, macrophages that are endowed with ACAID-inducing properties (by exposure to supernatants of iris and ciliary body cell cultures) preferentially migrate to the spleen following their intravenous inoculation into syngeneic recipients. Moreover, when injected intravenously into asplenic mice, macrophages with ACAID inducing potential accumulate excessively (compared to their conventional counterparts) in the peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303097 TI - Differential effect of aging on membrane immunoglobulin (mIg)-mediated endocytosis in the inductive and effector sites of the mucosal immune system. AB - The effect of aging on the endocytosis of anti-immunoglobulin (Ig) antibody as ligand by membrane Ig receptors (mIg) of B cells in the spleen, the mesenteric lymph nodes (MLN), and the Peyer's patches (PP) was investigated. Horse radish peroxidase (HRP) labelled (Fab')2 anti-mouse Ig specific for IgM, IgG, and IgA was used as the ligand. The rate of mIg mediated ligand endocytosis by aged B cells was significantly reduced in the PP as compared to the young group. In contrast, there were no age-related differences in the rate of mIg-mediated ligand endocytosis by B cells in the spleen and MLN. After 2 hr of incubation, about 70-80% of ligand added was internalized by splenic and MLN B cells from both young and old mice. Aged PP B cells showed significantly slower rate of ligand internalization as compared to those cells from young mice. This effect was pronounced at 30 and 60 min after incubation. Young PP B cells were found to internalize about 50% of the ligand within 30 min, while it took 60 min for aged B cells to internalize the same amount. The age-related rate of mIg-mediated endocytosis by B cells in the MLN, as opposed to a slower rate of endocytosis by B cells in the PP, emphasizes its distinct nature as a mucosal site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303098 TI - Adjuvant effects of freely ingested cholera toxin on systemic antibody and DTH responses to protein antigen. AB - Recent evidence suggests that immunological handling of antigen in the gut may be different when animals voluntarily ingest antigen in their drinking fluid. Therefore, we investigated whether the adjuvant effects of CT were evident in mice that voluntarily ingested CT together with keyhole limpet hemocyanin (KLH) in 1.0 ml chocolate milk. Initially, it was found that ingestion of 2 mg KLH for up to four times (one ingestion per week) did not induce serum IgG anti-KLH antibody; however, KLH-specific IgG was detected if KLH was ingested together with 10 micrograms CT. Furthermore, 50 days after only one ingestion of CT+KLH, the serum IgG response to intraperitoneal challenge with 100 micrograms KLH was significantly elevated with respect to the response of mice who previously had ingested either KLH alone, CT alone, or drinking fluid only. This observation was repeated in further experiments showing an enhanced IgG response to 100 micrograms KLH ip given 7 or 14 days after a single ingestion of 2 or 5 mg KLH mixed with different doses (0.5-20 micrograms) CT. The lowest effective CT dose for serum IgG anti-KLH adjuvanticity was found to be 1 microgram; the highest effective dose was 10 micrograms, there being no additive effect with 20 micrograms CT. It was also found that simultaneous ingestion of KLH (2 or 5 mg) with CT (0.5-20 micrograms) followed 7 or 14 days later by 100 micrograms KLH ip, increased the 24 hr footpad DTH response to 50 micrograms KLH administered 43 days after the ip challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303100 TI - [The microbiological purification of industrial sulfur-containing sewage]. PMID- 1303099 TI - Regional accumulation of Pgp-1+ memory cells in senescent mucosal immune system. AB - The proportion of memory cells expressing the Pgp-1 surface marker, and subsets of T cells expressing L3T4 (CD4+ helper cells), Lyt-2 (CD8+ suppressor/cytotoxic cells), LFA-1 (lymphocyte function-associated antigen-1), and interleukin-2 receptors (IL-2R) on the cell surface in the spleen, regional lymph nodes (PLN), mesenteric LN (MLN), bronchial or mediastinal LN (BLN), Peyer's patches (PP), thymus, and bone marrow (BM) was studied in C57BL/6J mice of varying ages. Monoclonal antibodies (Mabs) IM7.8.1, FD4, GK1.5, 3.155, and FD441.8 were used to measure Pgp-1, IL-2R, L3T4 Lyt-2, and LFA-1 expressions, respectively. Optimal dose and kinetic studies were determined. The percentages of positive cells were determined by monoclonal antibody staining and flow cytometry or immunofluorescence microscopy. Using flow cytometric analysis, we found significant age-associated increases in the percentages of Pgp-1+ cells in the MLN as compared with a slight, but not significant, increase in the spleen. There were significant age-related increases in the percentages of Lyt-2+ cells in the spleen with no change in the MLN. The percentages of cells with the other phenotypic markers, L3T4, LFA-1, and IL-2R did not change with age in the spleen or MLN. Using immunofluorescence microscopy, the percentages of Thy-1.2+, Lyt-1+, and Lyt-2+ cells in different anatomical immune tissues did not change with age, except in the BLN and PP where there were significant age-related declines of the percentages of Thy-1.2+ and Lyt-2+ cells in the BLN, and of Lyt-1+ cells in the PP. These results indicate elevated levels of Pgp-1+ memory senescent cells in the MLN and these age-related shifts or changes in T lymphocyte subsets with age could contribute to the conserved immune responsiveness of senescent mucosal T lymphocytes. PMID- 1303101 TI - [The stimulation of the delayed hypersensitivity reaction by the venom of the blunt-nosed viper Vipera lebetina and by its liposomal form]. AB - Native poison of middleasia viper Vipera lebetina has been included into liposomes in order to get an effective preparation for immunotherapy. The preparation reduces the risk of complications taking place during the use of traditional methods. The immunomodulating action of the liposomal form of viper poison has been investigated on the model of reaction of hypersensitivity of delayed type. Together with the stimulation of functional activity T-cells, the absence of suppressive and toxic actions while using the liposomal preparation of poison has been discovered. It is suggested that the observed stimulating effect in connection with immune reactions is due to synergism of action of components of poison liposomal form and activation of T-cells and macrophage, taking part in immune response to the antigenic stimulus. PMID- 1303102 TI - [The effect of hypoxia and of subsequent baro-oxygenation on the function of the microsomal oxidation system in the rat liver]. AB - The increase of cytochrome P-450 by 34% and its catalytic activity with substrate amidopyrine by 57% as compared with control has been shown under hypoxia (0.029 MPa, 1 h). Hyperoxia (0.2 MPa, 1 h) increases the metabolism of amidopyrine by 148%, benzo[a]pyrene by 158% and aniline by 114% and consecutive affection of hypoxia and hyperoxia--by 247, 45 and 138% correspondingly at fixed cytochrome P 450 amount in both series. The amount of diene conjugates and Schiff's bases under hypoxia increases by 40 and 69% correspondingly, the activity of SOD and catalase decreases by 25 and 23%. The activity of hyperoxia raises the diene conjugate content by 19% at all this SOD activity increases by 95%. Consecutive affection of hypoxia and hyperoxia increases the level of diene conjugates and Schiff's bases by 26 and 23% correspondingly, without changing SOD and catalase activity. The relative microsomal viscosity of lipid layer and zones of enzyme lipid contacts decreased by 20 and 24% under hypoxia, but under hyperoxia and consecutive affection and hypoxia and hyperoxia it increases by 29-28% and 56-40% correspondingly. PMID- 1303103 TI - Changes in the configuration and the dimensions of the fossa hypophysealis in the rat (Rattus rattus norvegicus) dependent on the age, weight and individual size of the skull. AB - The aim of our work was to describe the fossa hypophysealis in the most common laboratory animal--in the rat, to measure its dimensions, to determine its stereotactic coordinates and to find the dependence of these coordinates on the age, weight and individual size of the skull in different rats. From this measurement we obtained data on the growth and possible shifts of the fossa hypophysealis but also found data facilitating the selection of animals to stereotactic operations so that the hit of the hypophysis be the most probable. There are suitable coordinates for bilaterally stereotactic intervention into the middle female rats hypophysis in conclusions of our work. PMID- 1303104 TI - An electron microscopic study of the development of the thymus anlage of athymic (nu/nu) mice. AB - Using electron microscopy, we examined the anlage of dysgenetic embryo thymuses of nu/nu mice aged 14.5-15 days, 16 days and 18 days p.c., with thymus anlage of nu/+ mice serving as controls. On comparing both types, we noted differences at all intervals which increased in a time-related manner. Lymphoid cells were found only very occasionally in dysgenetic thymus anlage up to day 16 p.c. while there were no capillaries at all in any of the stages investigated. In epithelial reticular cells, undemarcated (membrane non limited) spaces of varying size and containing PAS+ material were found in the cytoplasm (glycogen-like particles seen in electron microscopy). Based on our findings, and on general assumptions, we believe that the primary process occurring in the dysgenetic thymus is abnormal epithelial stroma differentiation resulting not only in a lack of lymphoid cells but, also, in a limited or probably absent vascular bed. PMID- 1303105 TI - Ultrastructural changes of neurons in dependence on the death cause in human brain. AB - Autolytic changes in animal neurons 3 hours postmortem were compared with the changes in human material taken from the patients with ischemic heart disease. Relatively homogenous neuroplasm in the animal material was observed and the nuclei and nucleoli were present as well. Light artificial spaces were visible around the neurons. Marked vacuolization was in all cases of the human material. In some cases the nucleus with the nucleolus and mitochondria were still preserved. Majority of the neurons did not reveal the nucleolus and chromatin in their nuclei; destruction of the organelles and homogenization of the neuroplasm were dominant. We assume that the specific changes in the brain caused by the ischemic heart disease are different in comparison with the autolytic postmortal changes. PMID- 1303106 TI - Nigrostriatal projections in the rat as demonstrated by retrograde transport of horseradish peroxidase. II. Projection to the caudal striatum. AB - The distribution of nigral neurons projecting to the caudal and basal parts of the striatum was studied in 9 rats by means of the horseradish peroxidase labelling technique. Labelled neurons localized in the substantia nigra pars compacta were demonstrated throughout the antero-posterior extent of the nucleus. Most of them were found in the lateral half of the SNc. Labelled neurons localized in the substantia nigra part reticulata predominated in the caudolateral part of the SNr. Characteristic features included major perikaryal polymorphism and size range of the nigrostriatal neurons. PMID- 1303107 TI - Ultrastructural aspects of synaptic adaptability in human brain. AB - The ultrastructure of synapses in human brain which died with ischemic heart disease in various time after ischemic injury showed that the whole range of symptoms of compensatory character appears together with degenerative changes. The most important changes of presynaptic membrane consist of pinocytous invagination. Tubular structures in region of synaptic contact as well as on the surface of small invaginal axonal branches, dendrites and small spines are also found. We assume that plastic rebuilding of synapses have compensatory significance. PMID- 1303108 TI - The ependyma of the goat. III. Organum vasculosum hypothalami. AB - The presence of organum vasculosum hypothalami in the 3rd cerebral ventricle in goat has been confirmed. The surface of this organ is undulated, covered with cylindrical or cuboidal ependyma. Its rostral pole has simple, finger-shaped protrusions, the number of which increases during the "inactive" period (females: anestrus, males: out of season; both sexes: April), sporadically they occur in the mating season (females and males: October, November). Except for cilia and microvilli, no other supraependymal structures have been found. The organum vasculosum hypothalami of goats does not have dense capillary network and neither has "nucleus organi vasculosi hypothalami" been found. PMID- 1303109 TI - The state of the microcirculatory bed after total ischaemia of the brain. An experimental ultrastructural study. AB - The study was focused on the changes in morphological structure of cerebral microcirculation after two stages of 7 min dog's total brain ischaemia followed by 24 recirculation. In the first experimental group (brain blood pressure 2.5 3.0 kPa), there was observed ultrastructural picture of damaged microvessels, including dilated and irregularly shaped lumens, thick finger-like endothelial processes, dark osmiophilic cytoplasm of the endothelial cells with light spaces, clusters of ribosomal structures, impairment of endoplasmic reticulum and mitochondria, dilated tight junctions, irregular and thickened basement membranes. The alteration of astrocytes consisted of accumulation of beta glycogen particles and lipofuscin and altered lysosomal structures. On the other hand, in the second experimental group (brain blood pressure 1.0-1.5 kPa) the signs of impaired microcirculation were found. Type A pattern of vessel damage was delineated by dilated capillary lumen, despite the presence of marked perivascular oedema. Type B represented the no-reflow phenomenon. Type C was defined by a conspicuous lobular nucleus of endothelial cells obstructing the lumen of the capillary. Type D was characterized by ischemically damaged erythrocytes, despite the adequate perfusion fixation. Finally, type E included necrotic endothelial cells and endothelial blebs. PMID- 1303110 TI - A freeze-fracture study on the effect of neopybuthrin on the intestinal epithelial cells of Tilapia nilotica. AB - Freeze-fracture replicas of the plasma membrane and tight junctions (Tj) of intestinal epithelial cells were studied in Tilapia nilotica fish exposed to the pyrethroid insecticide, neopybuthrin. Exposing fishes to different repeated concentrations of 1/2 LC50 of neopybuthrin caused a significant decrease in the population density of IMPs in P- and E-faces. Tight junctions were also affected by neopybuthrin treatment. They appeared fragmented and discontinued, and their strands were fewer in number as compared with controls. Since the structure and number of Tj are major determinants of epithelial permeability, it is postulated that neopybuthrin treatment may affect the intestinal permeability of T. nilotica. PMID- 1303111 TI - The centenary of Prof. Mudr. Zdenek Frankenberger, DrSc. and his heritage for Czech morphologists. PMID- 1303112 TI - Study of the incidence of radicular grooves in maxillary incisors. AB - The purpose of this investigation was to determine the incidence of radicular grooves in the upper incisors of 642 patients from the region of Ribeirao Preto, SP, Brazil. Radicular grooves, present in 3.9% of the patients, were found mainly on the lingual surface of the maxillary lateral incisor (3.0%). The maxillary central incisors showed radicular grooves on both the buccal and lingual surfaces with an incidence of 0.9%. It was not possible to relate the incidence of these grooves with race (white and negro) or with sex. PMID- 1303113 TI - The effect of 1% chlorhexidine gel delivered with toothpicks on proximal dental plaque. A pilot study. AB - The aim of this study was to determine the effect of 1% chlorhexidine gel delivered with toothpicks on interproximal dental plaque. Seven follow-up patients participated in two treatment periods of 1 week each, separated by a normal oral hygiene period of one week. The study had double-blind design. The plaque index by Silness and Loe (Acta Odontol Scand 22: 121-135, 1964) was scored on mesial, distal, buccal and lingual surfaces of each tooth after plaque disclosure, with an aqueous solution of erythrosine and the measurements were performed by the same examiner, at the initial visit and at the end of every experimental week. The ability to use toothpicks was checked and upgraded to the individual need. The participants were instructed to carry out their normal oral hygiene procedures, with placebo gel or 1% chlorhexidine gel delivered interproximally with toothpicks once daily. No significant differences in the measurement of plaque were noted between placebo gel and 1% chlorhexidine gel at interproximal areas. After treatment with 1% chlorhexidine gel, the mean distribution of plaque score 0 was increased significantly (P < 0.05), from 30.7 sites (52%) to 42 sites (71.1%) when all sites are taken into account and compared to the placebo period. 1% Chlorhexidine gel delivered by toothpick on interproximal areas had a limited effect on reduction of dental plaque. PMID- 1303115 TI - The influence of gross caries removal and temporary filling of dental caries with a zinc oxide eugenol cement on the level of mutans streptococci in saliva. AB - The influence of gross caries removal and temporary filling of dental caries with a zinc oxide eugenol cement on the salivary level of mutans streptococci (MS) was studied in 14 children, 6 to 8 years of age. Forty-eight hours after filling all cavities, there was a significant decrease in the level of these cariogenic microorganisms. However, after 30 days, the salivary level of mutans streptococci was similar to that detected initially. PMID- 1303114 TI - Actinobacillus actinomycetemcomitans in Brazilian insulin-dependent individuals with diabetes mellitus. AB - The prevalence of Actinobacillus actinomycetemcomitans (Aa) in subgingival plaque specimens from 26 insulin-dependent diabetes mellitus patients, 11-25 years of age, was determined between January 1987 and December 1989. One hundred and thirty subgingival plaque samples were collected with sterile periodontal curettes. The specimens were weighted, diluted, inoculated on trypticase-soy serum-bacitracin-vancomycin agar medium (TSBV) and incubated under microacrophilic conditions. Aa was isolated from 2.3% of healthy periodontal areas in these patients, while the microorganism was found in 12.5% of the sites with gingivitis and in 2.6% of the periodontal pockets examined. Although biochemical tests used for the characterization of Aa strains showed homogeneous results, different biotypes were isolated from one or more periodontal sites in the same patient. PMID- 1303116 TI - Free autogenous cartilage grafts to the mandible of rats-histological study. AB - The present study was designed to histologically evaluate the behavior of free autogenous cartilage grafts to the mandible of rats. A 3-mm segment was removed from the last rib of male adult rats and transplanted fresh to a receptor bed prepared on the mandibular ramus. The results showed that the grafts maintained their vitality up to 120 days and the perichondrium was biologically integrated to the osseous bed. Appositional growth of the grafts was found. New bone formation was observed in close proximity to the grafts, but newly formed trabeculae did not arise from perichondrium. PMID- 1303117 TI - Method of preparing inter-mouth protectors as a means of preventing dental trauma. AB - A method of preparing individualized inter-mouth protectors for patients at risk of dental trauma or inclined to suffer trauma is presented. A totally individualized protector is more efficient for the protection and prevention of dental trauma. Two sessions with the patient were required. We conclude that the method was simple, observing all the necessary requirement for this type of device. PMID- 1303118 TI - Morphologic study of the maxillary molars. Part II: Internal anatomy. AB - The internal anatomy of three hundred and seventy (370) decalcified and cleared human maxillary molars was studied. Seventy-five percent of the first molars, 58% of the second molars and 68% of the third molars studied presented three (3) root canals and 25% of the first molars, 42% of the second molars and 32% of the third molars presented four (4) root canals. The authors observed that the incidence of two root canals in the mesiobuccal root was higher in second maxillary molars than in first maxillary molars. PMID- 1303119 TI - Odontomas--report of 3 cases. AB - Three clinical cases of odontoma were detected in 2 children and 1 adolescent. The tumors were surgically removed. Clinical suspicion was based on facial deformity in one of the cases and on the absence of permanent tooth eruption in the other two. Radiographic evidence of odontoma was confirmed through histological study. PMID- 1303121 TI - Morning meetings, the 10 minute secret to success. PMID- 1303120 TI - Benefits and usage of fluoride and fluoride supplements. PMID- 1303122 TI - The role of fluoride in the prevention and treatment of dental caries and other diseases. PMID- 1303123 TI - American Society of Preventive Oncology position statement on tobacco and nicotine dependence. PMID- 1303124 TI - Thwarting tobacco companies. PMID- 1303125 TI - Risk patterns of Hodgkin's disease in Los Angeles vary by cell type. AB - Over the period 1972-1985, 2729 cases of Hodgkin's disease were diagnosed in Los Angeles County, and 2492 were subclassified using the Rye classification. The occurrence of these cases was examined in relation to age, sex, race, place of birth, social class, occupation, and year of diagnosis. The pattern of nodular sclerosis occurrence conformed to expectations, supporting the polio model of etiology for this subtype. However, the risk pattern of mixed cell disease was quite distinct from that of nodular sclerosis, suggesting that the two may not share a common etiology. The pattern of lymphocyte predominance in Hodgkin's disease, with a special prominence in younger blacks, resembled neither that of nodular sclerosis nor that of mixed cell disease. The cases of lymphocyte depletion Hodgkin's disease showed no distinctive epidemiological features, and its continued classification with nodular sclerosis and/or mixed cellularity can be justified solely by histological or biological evidence. PMID- 1303126 TI - The association of diet, obesity, and breast cancer in Hawaii. AB - A case-control study of the association of dietary fat and animal protein consumption with breast cancer was conducted between 1975 and 1980 on Oahu, Hawaii. Data from this study were used to explore the relation of selected foods and the interaction of nutrients and foods with other factors, such as body size, age at menopause, and ethnicity on the risk for breast cancer. The sample included 272 postmenopausal breast cancer cases and 296 neighborhood controls. Study participants included Japanese and Caucasian women, aged 45 to 74, who were residents of Oahu. There was a suggestion of a positive-dose response relation (P < 0.01) between sausage consumption and the odds ratio for breast cancer. Significant odds ratios for breast cancer were also found for higher intakes (above the 50th percentile) of diary items, sausage, and all meats combined. The dose-response relation for nutrients and foods tended to be stronger among women with a high Benn's index (kg/cm1.5182) compared to women with a low Benn's index. In general, subjects with high dietary intakes of fat and animal protein who were in the upper 50th percentile of body size were at the greatest risk for breast cancer. However, there was no evidence for an interaction between the dietary variables and body size, ethnic group, age at menarche, age at menopause, or age at first birth that would affect the odds ratio for breast cancer. These data suggest that women with both a high intake of foods rich in fat and animal protein and with a large body size are at increased risk for breast cancer. PMID- 1303127 TI - The association of dietary fat with ability to obtain breast fluid by nipple aspiration. AB - The ability to obtain breast fluid by nipple aspiration was examined in relation to self-reported dietary fat intake in 1347 white and 153 black women. Study participants were between 20 and 59 years of age, were not pregnant or breastfeeding, and had no history of breast cancer. The proportion of women from whom nipple aspirate fluid was obtained increased with increasing dietary fat consumption; the odds ratio for obtaining breast fluid was 1.4 (95% confidence interval, 1.0-1.8) in white women who consumed over 90 g of fat/day compared with those who consumed less than 50 g of fat/day, adjusting for age, smoking, and parity. Among black women, the association was much stronger; the odds ratio for obtaining nipple aspirate fluid in those who consumed over 90 g of fat/day was 3.6 (95% confidence interval, 1.3-10.1) compared with those who consumed less than 50 g of fat/day. In both blacks and whites, the associations were most pronounced in women aged 30-44 years. These findings suggest a relationship between dietary fat consumption and breast secretion. PMID- 1303128 TI - Chromosome rearrangements in fumigant appliers: possible relationship to non Hodgkin's lymphoma risk. AB - Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6,138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2,533 metaphases in control subjects. Bands with significantly more breaks than expected based on band length in all study subjects were 1q32, 3p14, 7p15, and 14q11. Three of these four bands had significantly more breaks than expected in the exposed group, and all four bands had a significant excess of breaks in the control group. There are four bands with a significant excess of breaks in the exposed group and no breaks in the control group; each of these occurs in a known protooncogene region. These are 1p13 (NRAS), 2p23 (NMYC), 14q32 (ELK2), and 21q12 (ETS-2). Most breaks at bands 1p13, 14q32, and 21q22 are associated with chromosome rearrangements and occurred in appliers who have a mixed exposure to phosphine and other pesticides. Cytogenetic abnormalities, i.e., rearrangements and/or deletions involving bands 1p13, 2p23, and 14q32, are associated with non Hodgkin's lymphoma. We speculate that these findings could relate to the risk of evolution of a neoplastic clone in these workers. Epidemiological studies of similarly exposed workers indicate an excess of non-Hodgkin's lymphoma. PMID- 1303129 TI - Gastric intestinal metaplasia in ethnic groups in the southwestern United States. AB - The incidence of gastric cancer has declined dramatically in the United States during this century. However, the incidence of gastric cancer among Hispanics, Blacks, and Native Americans remains 2-3-fold higher than among Whites in this country. Populations with an increased risk of gastric cancer have predominantly the "intestinal" type of gastric cancer, and intestinal metaplasia is regarded as a histological precursor lesion of this type of gastric cancer. We sought to establish the prevalence of intestinal metaplasia, identify associated epidemiological factors, and improve detection of this lesion in a patient population undergoing clinically indicated endoscopy in the Southwestern United States. Among the 440 patients studied, we observed an overall crude prevalence of intestinal metaplasia of 19%. However, the crude prevalence among Hispanics and Blacks was found to be markedly higher than among non-Hispanic Whites (50% versus 13%). Two biopsy protocols (two biopsies versus four biopsies) were used during this study, with a significantly higher rate of intestinal metaplasia detection under the four-biopsy protocol. Adjusting for protocol, we found that age and ethnicity were significantly and independently associated with the prevalence of intestinal metaplasia. The odds of intestinal metaplasia diagnosis was significantly higher in Hispanics compared to non-Hispanic Whites (P < 0.001), and the prevalence of intestinal metaplasia increased with advancing age (P = 0.01). The presence of Helicobacter pylori was also significantly associated with the presence of intestinal metaplasia (P = 0.02), although the direction of the association differed between Hispanics and non-Hispanic Whites. PMID- 1303130 TI - Determinants of plasma ascorbic acid in a healthy male population. AB - The antioxidant properties of vitamin C may be involved in the prevention of cancer. The correlation between dietary vitamin C intake as estimated by a dietary questionnaire and plasma ascorbic acid (AA) was examined in 68 nonsmoking male volunteers aged 30-59 years. Determinants of plasma AA as well as interrelationships between various antioxidants in plasma were also explored. The determinants of plasma AA were examined by a multiple regression model containing dietary vitamin C, calories, body weight, and amount of beverages consumed. Higher vitamin C intake (P < 0.0002) increased plasma AA, while greater body weight (P < 0.005) decreased plasma AA. A significant correlation (r = 0.43; P < 0.0003) between vitamin C intake and plasma AA was observed. There was a negative correlation between plasma AA and plasma uric acid (r = -0.32; P < 0.007) and positive associations between plasma beta-carotene and plasma alpha-tocopherol (r = 0.39; P < 0.001) and between plasma beta-carotene and plasma glutathione peroxidase (r = 0.32; P < 0.008). Vitamin C supplement users had higher plasma AA compared to nonusers. The relationship between plasma AA and vitamin C intake appears to be curvilinear with the non-supplement users at the linear part of the curve and the supplement users at the plateau. Plasma AA is an appropriate biomarker, in our subjects, of dietary vitamin C except for people consuming large amounts of this vitamin either in their diet or in supplemental form. PMID- 1303131 TI - Evaluation of a test for abnormal rectal mucus for early detection of colon cancer. AB - This report describes the evaluation of a chemical test for T-antigen in rectal mucus as a screening test for colon cancer. The test, called the Mucus Strip Test, detects the disaccharide residue sialic acid-free beta-D-Gal(1-->3)-D GalNAc or T-antigen, which accumulates in mucus from malignant cells and colonic mucosa adjacent to cancer but not in normal mucosa. Participants were an unselected case series of 660 persons undergoing colonoscopy, excluding those with ulcerative colitis, polyposis, Crohn's disease, or nonspecific inflammatory bowel disease. In the first study (n = 608) rectal mucus was collected after preparation of the bowel for colonoscopy; in the second study (n = 52) a modified protocol was used to collect mucus approximately 2 weeks before colonoscopy and again following preparation for the procedure. Mucus Strip Test results were compared to the diagnosis received after colonoscopy, which was classified as cancer, adenomatous polyp(s), and others (normal). Analyses were also stratified by previous history of large intestinal disease, classified as previous cancer; previous diagnosis of adenomatous polyp(s); or others. In the first study, T antigen was detected in approximately 30% of mucus samples, and test results were independent of both diagnosis at colonoscopy and previous medical history. In the second study, T-antigen was detected in 85% of samples collected before and 96% of samples collected after preparation for colonoscopy, but test results were again independent of diagnosis and medical history.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303132 TI - Isolation and characterization of two benzene-derived hemoglobin adducts in vivo in rats. AB - The present study was aimed at the characterization of the major adducts formed by reaction of the metabolites of [14C]benzene with rat hemoglobin in vivo. Groups of 12-week-old male Fisher rats received i.p. injections of a single dose of 10 mmol/kg body weight or three equal daily subdoses of 3.3 mmol/kg body weight of [14C]benzene. High-performance liquid chromatographic analysis of strong acid hydrolysates of the [14C]benzene-modified globin indicated that the two major adducts in rats cochromatographed with synthetic S-(2,5 dihydroxyphenyl)cysteine and S-phenylcysteine. These adducts were converted to O,O'-S-tris-acetyl-3-thiol-hydroquinone and S-phenylthioacetate, which were then characterized by gas chromatography/mass spectrometry. The major radioactive adduct peaks accounted for 60-75% of the total radioactivity associated with rat globin. Characterization of the S-(2,5-dihydroxyphenyl)cysteine adduct provides evidence that p-benzoquinone is formed as a reactive metabolite of benzene. Formation of the S-phenylcysteine adduct indicates that benzene oxide and/or a hydroxycyclohexadienyl free radical is formed as an active intermediate upon i.p. injection of benzene into rats. PMID- 1303133 TI - Patients' perceptions on participation in a cancer chemoprevention trial. AB - The perceptions of patients regarding the benefits, disadvantages, and importance of their participation in a long-term cancer chemoprevention trial, the Isotretinoin-Basal Cell Carcinoma Prevention Trial, were assessed through a questionnaire mailed at the conclusion of the 3-year treatment period of the trial. Responses were evaluated overall, as well as within subgroups defined by sex, age, education level, treatment group, presence of side effects, and the number of skin biopsies performed during the 3-year intervention phase. Overall, "careful medical follow-up received" (43%) and "being part of a research effort" (24%) were the most frequently cited important benefits, while the "amount of time taken to attend clinic" (32%) and "side effects" (20%) were the most frequently cited unpleasant aspects of trial participation. Most surveyed patients viewed the study as "very or extremely important" to their general health (62%) and their skin cancer condition (88%) and, as a result of participation, felt "much or somewhat better" physically (52%). The majority indicated that they would "definitely or probably" be willing to take part in another research study (79%) and take the study medication, if it were shown to be effective in the trial (78%). Overall and subgroup data provide important insights into patient motivations and attitudes regarding cancer chemoprevention trial participation, adherence, and satisfaction. PMID- 1303134 TI - Correspondence re: E.T.H. Fontham et al., lung cancer in nonsmoking women: a multicenter case-control study. Cancer epidemiol., biomarkers & prev., 1: 35-43, 1991. PMID- 1303135 TI - Correspondence re: E.T.H. Fontham et al., lung cancer in nonsmoking women: a multicenter case-control study. Cancer epidemiol., biomarkers & prev., 1: 35-43, 1991. PMID- 1303136 TI - Phospholipid methylation and taurine content of synaptosomes from cerebral cortex of developing rat. AB - Changes in taurine concentration and rate of methylation of phosphatidylethanolamine have been examined in rat brain synaptosomes over the course of development. At 7, 14, 21, 28 and 56 days of age, rats were injected i.p. with 300 microCi/kg [3H-methyl]methionine. Synaptosomes (P2B fraction) were isolated from the cerebral cortex 9 h later and incorporation of the methionine methyl group into phospholipid and protein was investigated. Synaptosomal taurine and methionine concentrations were determined at the same ages, as were the concentrations of the major classes of phospholipids (phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine and phosphatidylserine). Methionine concentration increased between day 7 and 14 and fell thereafter. Phospholipid methylation rates calculated from the specific activity of synaptosomal methionine were high from days 7 and 14 and then fell, whereas protein methionylation increased between day 7 and 28 and then decreased. A strong correlation was found between the taurine concentration of the synaptosome and phospholipid methylation rates during brain development. Protein methionylation rates, however, showed no correlation with taurine concentration. PMID- 1303137 TI - Regulatory role of a neurotransmitter (5-HT) on glial Na+/K(+)-ATPase in the rat brain. AB - In the present work we studied the effect of serotonin (5-HT) on the kinetics of Na+/K(+)-ATPase in subcellular preparations of the cerebral cortex from male Wistar rats using various concentrations of ATP and K+ with and without added 5 HT. Also we studied the effect of 5-HT on the enzyme in glial or neuronal preparations. The results indicated that there was a significant increase (P < 0.05) of the Vmax in the presence of 5-HT in the whole tissue preparation (homogenate) but not in the subcellular fractions, suggesting that the interaction could be preferentially with the glial pump. Further results supported that this was the case since activation by 5-HT was mainly in the glial preparations. Kinetic data and the binding of [3H]ouabain supported that the enzyme is activated by 5-HT through the exposure of more enzymatic active sites. PMID- 1303138 TI - Glial cells in coculture can increase the acetylcholinesterase activity in human brain endothelial cells. AB - The elements of the cholinergic system (acetylcholinesterase and choline acetyltransferase) and butyrylcholinesterase were studied in human cortical capillary samples, brain-derived endothelial cell cultures and glial cell cultures. It was shown that the elements of the cholinergic system are present in the microvessels, but the choline acetyltransferase activity may be due to contamination with cholinergic nerve terminals since no choline acetyltransferase could be demonstrated in endothelial cell cultures. The present results revealed that the activity of acetylcholinesterase is reduced in the cortical endothelial cell cultures after longer culture times, while butyrylcholinesterase activity is not altered. In a system where endothelial cells were cocultured with embryonic human brain astroglial cells for 12 days in vitro, the acetylcholinesterase activity was increased 2-fold. These results support a glial influence on the enzyme activity of the cerebral endothelium. PMID- 1303139 TI - Isolation and characterization of hamster brain polyribosome-cytomatrix complexes. AB - We have developed a method for the isolation of a brain subcellular fraction enriched in both highly aggregated polyribosomes and cytoskeletal proteins. This method is based on gentle dispersion of brain tissue and low speed centrifugation. This fraction is enriched in typical cytoskeletal proteins as glial fibrillary protein, neurofilament proteins and actin. Messenger RNA did not seem to be involved in the polyribosome association to the cytomatrix as shown by the effect of exposure to micrococcal nuclease. On the other hand, in vivo disruption of protein synthesis by acute experimental phenylketonuria, hypothermia or heat-shock did not cause the release of ribosomes from the cytomatrix. PMID- 1303140 TI - In vitro neurotransmitter release in an animal model of depression. AB - Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent shock escape test into two groups: a "helpless" (LH) group which demonstrates a deficit in escape behavior, and a "nonlearned helpless" (NLH) group which shows no escape deficit and acquires the escape response as readily as naive control rats (NC) do. The present studies were designed to examine the correlations between the behavioral differences and the changes of in vitro neurotransmitter release seen in these three groups of rats. The major finding concerned a significant increase in endogenous and K(+)-stimulated serotonin (5 HT) release in the hippocampal slices of LH rats. There were no apparent differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock. PMID- 1303141 TI - Increased cardiac production of dihydroxyphenylalanine (DOPA) during sympathetic stimulation in anaesthetized dogs. AB - Entry of dihydroxyphenylalanine (DOPA) into plasma from specific organs may reflect regional activity of tyrosine hydroxylase, the enzyme responsible for the immediate synthesis of DOPA and rate-limiting for subsequent formation of catecholamines. Therefore, cardiac spillovers of DOPA, noradrenaline and the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), were examined during two periods of graded electrical stimulation of the sympathetic nerves to the heart in anesthetized dogs. Responses were examined before and after neuronal uptake blockade with desipramine. Cardiac spillover of DOPA increased by 1.8- and 4.4-fold during sympathetic stimulation before desipramine and by 1.6- and 3.3-fold after desipramine. Fold increases in cardiac spillover of DOPA were much lower than but positively related with fold increases in noradrenaline spillover (5.9- and 13.8-fold increases before and 9.0- and 15.8 fold increases after desipramine). Increases in cardiac spillover of DHPG (1.5- and 2.3-fold increases) were blocked by desipramine so that fold changes in spillover of DOPA were greater than and poorly related to changes in spillover of DHPG. Fold increases in cardiac spillover of DOPA showed a close one-to-one positive relationship with fold increases in the sum of cardiac spillovers of noradrenaline and dihydroxyphenylglycol before and after desipramine. For a given fold increase in noradrenaline release, transmitter turnover is increased fractionally and noradrenaline synthesis need also only increase fractionally to maintain transmitter stores constant. The close relationship between fold increases in cardiac spillover of DOPA and combined spillovers of noradrenaline and DHPG is consistent with regulation of tyrosine hydroxylase activity to match changes in noradrenaline synthesis with changes in noradrenaline turnover. Changes in cardiac spillover of DOPA appear to reflect local changes in tyrosine hydroxylase activity. PMID- 1303142 TI - [Leu31-Pro34] neuropeptide Y identifies a subtype of 125I-labeled peptide YY binding sites in the rat brain. AB - Subtypes of the neuropeptide Y (NPY) receptor in the rat brain were identified by the use of the selective Y-1 analog, [Leu34-Pro34] NPY. In rat brain homogenate binding studies, [Leu31-Pro34] NPY was found to produce a partial inhibition of 100 pM 125I-labeled peptide YY (PYY) binding with a plateau at 50-1000 nM [Leu31 Pro34] NPY resulting in a 70% inhibition of binding. The C-terminal fragment NPY 13-36, a putative Y-2 agonist, exhibited very little selectivity in rat brain homogenates. Scatchard analysis of 125I-labeled PYY binding to rat brain homogenate yielded biphasic plots with Kd values of 40 and 610 pM. Inclusion of 100 nM [Leu31-Pro34] NPY was found to eliminate the low affinity component of 125I-labeled PYY binding leaving a single, high affinity binding site with a Kd of 68 pM. In autoradiographic studies, displacement curves indicated that [Leu31 Pro34] NPY completely inhibited binding in the cerebral cortex with little effect on the binding in the hypothalamus. On the other hand NPY 13-36 inhibited binding in the hypothalamus at low concentrations but required higher concentrations to inhibit binding in the cerebral cortex. Other brain regions such as the hippocampus, appeared to contain both subtypes. Subsequent to these studies, a quantitative autoradiographic map was conducted using 50-100 pM 125I-labeled PYY in the presence and absence of [Leu31-Pro34] NPY which produced a selective displacement of binding in certain distinct brain regions. These areas included the cerebral cortex, certain thalamic nuclei and brainstem while ligand binding was retained in other brain regions including the zona lateralis of the substantia nigra, lateral septum, nucleus of the solitary tract and the hippocampus. Numerous brain regions appeared to contain both receptor subtypes. Therefore, the Y-1 and Y-2 receptor subtypes exhibited a somewhat distinct distribution in the brain. In addition, 125I-labeled PYY appears to label the Y-2 receptor with relatively higher affinity when compared to the Y-1 receptor. PMID- 1303143 TI - A pharmacological comparison of [3H]GBR12935 binding to rodent striatal and kidney homogenates: binding to dopamine transporters? AB - Binding of [3H]GBR12935 to homogenates of mouse and rat striatum and kidney was studied. [3H]GBR12935 bound to both tissue preparations with high affinity (mouse striatum Kd = 2.4 +/- 0.4 nM, n = 4; mouse kidney Kd = 3.8 +/- 0.9 nM, n = 4), in a saturable (striatal Bmax = 1.5 +/- 0.4 pmol/mg protein; kidney Bmax = 4.9 +/- 0.5 pmol/mg protein) and reversible manner. Saturation experiments revealed the presence of a single class of high affinity binding sites in both tissues of both species. Mouse kidney appeared to possess a greater density of [3H]GBR12935 binding sites than the striatum while the reverse situation prevailed for the rat. Although two dopamine uptake inhibitors, namely GBR12909 and benztropine, displaced [3H]GBR12935 binding from striatal and kidney homogenates with a similar affinity in both tissues of these species, unlabelled mazindol, (+/ )cocaine, nomifensine and amfonelic acid were significantly (P < 0.001-0.02) more potent inhibitors of [3H]GBR12935 binding in the striatum than in the kidney. While the pharmacological profile of [3H]GBR12935 binding in the rodent striatum compared well with that of the dopamine transporter reported previously, the pharmacology in the kidney was considerably different to that in the striatum. GBR12909 (1-30 mg/kg, i.p.), a close analog of GBR12935, induced significant antidiuretic and antinatriuretic effects in spontaneously hypertensive rats. These data suggest that while [3H]GBR12935 labels the dopamine uptake sites in the brain, it does not appear to label similar sites in the kidney. The mechanism of action of GBR12909 on sodium and water excretion remains to be determined. PMID- 1303144 TI - Fluorescence digital image analysis of thrombin and ADP induced rise in intracellular Ca2+ concentration of single blood platelets. AB - Cytoplasmic free Ca2+ concentration, [Ca2+]i, was estimated in single rabbit blood platelets by digital imaging microscopy with the use of the specific Ca(2+) indicator dye Fura-2. Uneven distribution and low level of [Ca2+]i was found in the resting platelet even in the presence of extracellular 1 mM Ca2+. Thrombin at 1 unit/ml immediately caused a transient increase in [Ca2+]i, which was followed by a secondary and sustained increase in [Ca2+]i. The distribution of increased levels of [Ca2+]i was also shown to be uneven within the cell. The presence of 1 mM EGTA in the medium only slightly decreased the initial rise in [Ca2+]i, but completely inhibited the latter phase, a sustained rise in [Ca2+]i. This result shows that the initial rise of [Ca2+]i might not be caused by Ca2+ influx, but might be induced by mobilization of Ca2+ from intracellular Ca2+ storage sites. This speculation is further supported by the fact that the elevated [Ca2+]i induced by thrombin immediately decreased to the base line value when 3 mM EGTA was applied. Thus, thrombin induced elevation of [Ca2+]i is suggested to consist of two different processes, namely the mobilization of Ca2+ from the intracellular storage sites and the successive Ca2+ influx through the receptor activated Ca2+ channels. Stimulation with ADP also caused a rapid elevation of platelet [Ca2+]i, but this effect of ADP was different form that of thrombin. Thus, the ADP induced rise in [Ca2+]i was accompanied by oscillation and was inhibited by extracellular EGTA. Our present experiment is the first report that clearly and directly reveals the differences between the effects of thrombin and ADP on [Ca2+]i of platelets. PMID- 1303145 TI - Effect of N,N'-dicyclohexylcarbodiimide on the binding of vesamicol, an inhibitor of acetylcholine transport into synaptic vesicles. AB - Vesamicol is a highly potent inhibitor of active acetylcholine transport into isolated cholinergic vesicles from Torpedo. On the basis of transport kinetics and vesamicol sensitivity, we have shown that the acetylcholine transporter could be in an activated state even in the absence of a stimulated ATPase. In this preparation, N,N'-dicyclohexylcarbodiimide (DCCD), an hydrophobic carbodiimide, inactivates both ACh transport and vesamicol binding. Inhibition of vesamicol binding by DCCD is time dependent, saturable and prevented by vesamicol. DCCD first affected the affinity constant for vesamicol. Ki-value for DCCD lies in the micromolar range. These results imply that there is a DCCD reactive site within the ACh transporter and that it is located in an hydrophobic environment near the vesamicol binding site. SDS-gel electrophoresis after labelling of the vesicle membrane proteins with [14C]DCCD shows that radioactivity is mainly incorporated in a 15 kDa subunit. Time-course and concentration dependence of [14C]DCCD labelling and vesamicol inhibition do not coincide. Hence, the two processes are probably unrelated and the result rather points to another inactivation mechanism which can be an intramolecular cross link. PMID- 1303146 TI - Different effects of L-, N- and T-type calcium channel blockers on striatal dopamine release measured by microdialysis in freely moving rats. AB - Using a microdialysis method, we have investigated effects of the voltage dependent calcium channel blockers, verapamil, nicardipine, omega-conotoxin and flunarizine on the dopamine release and metabolism in the striatum of freely moving rat. Perfusion of verapamil (1-300 microM) and nicardipine (1-100 microM), an L-type calcium channel blocker, into the striatum through the dialysis membrane showed a dose-dependent decrease of dopamine release in the dialysate and slight increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Treatment of omega-conotoxin (0.1, 1 microM), an N-type channel blocker, decreased about 50% basal dopamine release and slightly decreased DOPAC and HVA levels. Treatment with flunarizine (10 microM), an T-type channel blocker, did not affect the dopamine release and metabolism. From these data, it appears that treatments of the L- and N-type voltage-dependent calcium channel blockers in rat striatum suppress basal dopamine release, but T-type blocker does not suppress it, suggesting that L-, N- and T-type calcium channels regulate in vivo dopamine release in a different mechanism. PMID- 1303147 TI - Secretion of peptidylglycine alpha-amidating monooxygenase (PAM) from rat salivary glands. AB - Peptidylglycine alpha-amidating monooxygenase (PAM) is a regulating enzyme to synthesize the biologically active hormones having carboxy-terminal amide. In the present study we investigated secretion of the enzyme from rat saliva. Property of PAM in the saliva was similar to that in the submandibular gland. Both enzymes showed similar pH optimum at 5.0 and optimal ascorbic acid concentration at 2.5 mM. But molecular size of PAM in the saliva was 75 kDa in the gel permeation chromatography on Superose 12 column, while the size in the submandibular gland was 25 kDa. After the treatment with trypsin, PAM in the saliva was converted to a small size molecule, which is similar to the size in rat submandibular gland. These and other data indicate that a native molecular size of PAM is secreted into saliva and plays some physiological roles. PMID- 1303148 TI - Molecular characterization of D2 dopamine-like receptors from brain and from the pituitary gland. AB - D2 dopamine-like receptors have been purified from five bovine brain regions (caudate nucleus, putamen, olfactory tubercle, frontal cortex, cerebellum) and the anterior and neurointermediate lobes of the pituitary gland using a combined ligand-affinity and lectin-affinity chromatography procedure. In all the brain regions except cerebellum and in the neurointermediate lobe of the pituitary gland the purified species appeared as a M(r) 95,000 doublet on SDS-PAGE. In the anterior lobe of the pituitary an additional M(r) 142,000-145,000 species was seen. The M(r) 95,000 species had a low affinity for the lectin wheat germ agglutinin (WGA) whereas the M(r) 142,000-145,000 species had a higher affinity for WGA and additionally showed some affinity for concanavalin A. It is concluded that both the M(r) 95,000 and 142,000-145,000 species are D2 dopamine-like receptors and that the differences between the species are mainly at the oligosaccharide level. Some evidence was also obtained for heterogeneity at the protein level which may correspond to the D2(short) and D2(long) isoforms of these receptors. PMID- 1303149 TI - Myelin isolation: comparison of sedimentation and flotation techniques. AB - Brains from young (20 day old) and adult rats were used to compare myelin yields obtained by sedimentation and flotation techniques. The flotation method consistently gave approx 70% higher yields of myelin than the sedimentation method. Both myelin preparations have virtually identical protein composition as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoretic analysis revealed substantial concentrations of myelin proteins in the non-myelin particulate fraction obtained by the sedimentation but not by the flotation method. The study indicates that the paradigm of the sedimentation method results in a significant loss of myelin during isolation, and that this loss can be avoided or minimized by employing the flotation method. PMID- 1303150 TI - Nonenzymatic incorporation of glucose and galactose into brain cytoskeletal proteins in vitro. AB - Initial studies demonstrated the loss of lysine and simultaneous appearance of glucitollysine in intracellular proteins following incubation with sugar. For example, when a crude nervous tissue cytoskeletal preparation was incubated in 100 mM glucose for 10 days, > 60% of the lysine residues were modified. Over 20% of the lysyl residues in a spinal cord neurofilament preparation are susceptible to Schiff base formation after one day and over 30% following five days of incubation with 100 mM glucose. When incubated with 100 mM galactose, F- and G actin were found to be significantly modified in as few as 15 h, with > 70% of the lysyl residues lost. After 45 h of incubation, > 90% of the residues had been modified. These data also indicate that many of the lysyl residues in F- and G actin are exposed and very susceptible to modification by sugar. This rapid and extensive modification of lysine in actin in vitro suggest that it may be modified in diabetic nervous tissue. PMID- 1303151 TI - Identification of glucocorticoid responsive elements (GREs) at far upstream of rat NPY gene. AB - The location of three glucocorticoid responsive elements (GREs) in rat neuropeptide Y (NPY) gene was determined by chloramphenicol acetyltransferase (CAT) assay and nucleotide sequencing. We have reported that mRNA content of rat prepro-NPY is increased by 1.7-fold in NG108-15 cells by 1 microM dexamethasone, suggesting the presence of GRE in the gene. To identify the element, the 5' flanking DNA of 3.3 kilobases (kb) was isolated from rat NPY gene. When chimeric chloramphenicol CAT plasmids containing various deletions of the NPY upstream sequence were transfected into NG108-15 cells, the region between -2.9 and -2.1 kb relative to the cap site was found to potentiate the transcription of CAT gene in the presence of 1 microM dexamethasone. The nucleotide sequencing of this region revealed three GRE consensus sequences at -2.5, -2.2 and -2.1 kb. The results indicate that these elements present in the far upstream region of the NPY gene confer induction by glucocorticoids. PMID- 1303152 TI - Decreased prostaglandin synthesis in postmortem cerebral cortex from patients with Alzheimer's disease. AB - The syntheses of prostaglandin (PG) F2 alpha, E2 and D2, and thromboxane (TX) B2 from [14C]arachidonic acid were studied in frontal cortex of human control and Alzheimer's disease (AD) brains using the microsomal fractions. Under the assay conditions employed, it was found that the major metabolite of [14C]arachidonic acid was PGE2 accounting for 63% of total prostanoid production; PGF2 alpha accounted for 21.5%, TXB2 for 9%, and PGD2 for 6.5%. When AD samples were compared to control samples, microsomal PG synthesis was significantly decreased, with reduced production of PGE2, PGF2 alpha and PGD2. Such decreases in AD brain seem unrelated to age, sex, postmortem delay and, as far as could be determined, antemortem state. In both control and Alzheimer groups, a history of anti inflammatory therapy seemed to correlate with increased PG synthesis. PMID- 1303153 TI - [35S]t-butylbicyclophosphorothionate binding sites in susceptible and cyclodiene resistant houseflies. AB - 4-aminobutyric acid (GABA)-gated chloride ion channels are important molecular targets for a number of polychlorocycloalkane compounds including cyclodiene insecticides. Previous radioligand binding studies have indicated that cyclodiene insecticides are potent inhibitors of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to housefly thorax and abdomen membranes. In the present study, a laboratory-reared, cyclodiene-resistant (CYW) housefly strain (Musca domestica) showed resistance to a number of cyclodiene insecticides. Specific, saturable [35S]TBPS binding was detected in thorax and abdomen membranes prepared from housefly strains susceptible (CSMA) and resistant (CYW) to cyclodienes. Scatchard analysis of [35S]TBPS binding data from CSMA and CYW membranes revealed no significant differences between the two strains in either the affinity (Kd) or the density (Bmax) of specific, saturable binding sites. There were no differences in the comparative effectiveness of a range of polychlorocycloalkanes, including cyclodiene insecticides, as inhibitors of specific [35S]TBPS binding to CSMA and CYW thorax and abdomen membranes. Therefore, if an alteration in target site is a mechanism for resistance to cyclodienes in the CYW strain, it is not readily measurable using [35S]TBPS. PMID- 1303154 TI - Rat brain fatty acid-binding protein during development. AB - Cytosolic fatty acid-binding proteins (FABPs) have been described in rat and bovine whole brain. In the present study we investigated the distribution of FABP among white matter and gray matter as well as its changes during development. Fatty acid binding activity was similar in white and gray matter up to 40 days of age. In white matter it showed an age dependent increase thereafter, while in gray matter it remained constant throughout. Gel filtration (Sephadex G-75) of white matter cytosol of adult female rats resolved the fatty acid-binding activity in two peaks: A (Vo) and B (12-14 KDa; FABP). The specific binding activity in the FABP fraction was 10.4 pmol/micrograms of protein. The activity in peak A showed an age-dependent increase which paralleled myelin deposition. In contrast, the activity in the FABP fraction (peak B) remained undetectable up to 40 days of age, increasing thereafter. The differential distribution of cellular brain proteins with the capacity to bind fatty acids in gray matter and white matter suggests that this activity could be related to glial cells or to cell related structures such as myelin. PMID- 1303155 TI - How much undernourishment is required to retard brain myelin development. AB - This study employs a large population of developing rats designed to range continuously from above a normal, average weight to severely undernourished. The purpose of the study is to determine if brain myelin development is vulnerable to mild growth retardation from chronic hunger, or if brain myelin development is altered only after a certain tolerable amount of growth retardation is exceeded. The brains were examined at a landmark age, weaning, since myelination is one of the most vulnerable features of brain development and its rate of synthesis is highest at this age. Brain size was logarithmically related to body weight, and brain growth retardation increased as the severity of food deprivation increased. There was an additional reduction in the concentration of brain myelin. In contrast to brain weight, the reduction in myelin concentration was linearly related to body size over the full range from well nourished to undernourished. From a population perspective, these data indicate growth retardation from undernourishment in any amount slows brain growth and additionally lowers the concentration of brain myelin; however, individuals, in both well nourished and undernourished groups, vary widely. Implications and cautions of extrapolation to human populations are discussed. PMID- 1303156 TI - Expression of cloned aromatic L-amino acid decarboxylase in Xenopus laevis oocytes. AB - Sense mRNA coding for bovine adrenal medulla aromatic L-amino acid decarboxylase (AADC) was expressed following microinjection into Xenopus laevis oocytes. The expressed enzyme activity was stereoselective for L-5-hydroxytryptophan and L DOPA and blocked by NSD-1015 an inhibitor of AADC. Heating the expressed enzyme at 55 degrees C resulted in a parallel loss of activity towards both substrates. Our findings are consistent with the prevailing notion that a single enzyme is able to decarboxylate both substrates in vivo. PMID- 1303157 TI - Development modulates the serum induced effect on the incorporation of [2 3H]mannose into chick optic lobe protein: the possible role of glia. AB - Recently, we described that serum decreases tritiated mannose incorporation into protein in the chick optic lobe at 18 days of embryonic age (Rossi et al., 1990). In this paper, we found a strikingly different response of this serum effect according to age. The data obtained showed no serum induced decrease in 6-10-day old embryo. In addition, our results demonstrate that the differential response of the tissue to the serum is independent of the rate of sugar entry into nerve cells. Furthermore, we also report that the variation of mannose or leucine incorporation into protein coincides very closely with the pattern of protein and glycoprotein accumulation during chick optic lobe development. Finally, data were obtained to define glial cells as the cellular target of the serum induced effect. This finding may contribute to elucidate the mechanism of cellular pathogenesis of cerebral lesions that occur after the breakdown of the blood brain barrier, such as in some diseases or during bleeding after injuries. PMID- 1303158 TI - Phospholipid composition of oligodendroglial cells during normal development and in 18 day old hyperthyroid and malnourished rats. AB - The phospholipid composition of isolated oligodendroglial cell perikarya was studied in normal rats during development and in 18 day old malnourished and hyperthyroid rats. Phosphatidyl choline and phosphatidyl ethanolamine were found to be the major phospholipid constituents of oligodendroglial cells. Phospholipid content increased during development, mainly due to an increase of the above mentioned phospholipids. The major changes were observed in sphingomyelin, phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine between 18 and 30 days of age. The phospholipid and protein content per cell was significantly decreased in the oligodendroglial cells isolated from malnourished rats as compared to controls. When data were expressed as a function of total proteins, the composition was similar to that of normal animals. In the hyperthyroid rats on the other hand, there were no changes in the amount of phospholipids per cell, while phospholipids per milligram of total oligodendroglial cell protein were markedly decreased. The changes in myelin composition produced by hyperthyroidism that we have previously described, do not follow closely those produced by this experimental condition in oligodendroglial cells, suggesting that the metabolism of myelin might be to a certain extent, independent of that in the parent cell. PMID- 1303159 TI - Muscarinic cholinergic receptor binding in rat hindlimb somatosensory cortex following partial deafferentation by sciatic nerve transection. AB - Peripheral nerve injury or amputation leads to extensive changes within the central representations of the mammalian body surface. The mechanisms responsible for post-traumatic reorganization of these maps in adults may also, at least partly, underlie a more general feature of the somatosensory system--the capacity for stimulus-dependent plasticity. Acetylcholine has been implicated in both of these processes. We studied the binding of the ligands [3H]QNB and [3H]pirenzepine in rat hindlimb somatosensory cortex from 1 to 14 days following sciatic nerve transection. Although the [3H]QNB binding was not different from normal levels in tissue homogenates of the affected somatosensory cortex, differences were demonstrated when binding was measured on a layer-by-layer basis. [3H]QNB binding was changed only in certain layers, at certain times. The predominant effects appeared to be a decrease in binding in the middle layers from 4 to 14 days after the transection. Combining the [3H]QNB data with data obtained from the more M1-selective ligand [3H]pirenzepine suggested that complex changes occur among several muscarinic receptors, including receptors with non-M1 subtype characteristics. Moreover, unilateral nerve transection affects the hindlimb somatosensory regions in both hemispheres. PMID- 1303160 TI - Memantine stimulates inositol phosphates production in neurones and nullifies N methyl-D-aspartate-induced destruction of retinal neurones. AB - Whereas carbachol, noradrenaline, serotonin and memantine stimulated inositol phosphates production and calcium mobilization in 3-5 day old rabbit retinal cultures, only carbachol and noradrenaline were effective when 25-30 day old cultures were used. The older retinal cultures contain only Muller cells which shows that the memantine and serotonin effects on the 3-5 day old cultures are specifically associated with neurones. While the carbachol, noradrenaline and serotonin effects were respectively blocked by atropine, prazosin and ketanserin, none of these substances influenced the memantine responses. In all areas of the rat brain which were analysed, the effectiveness of memantine, noradrenaline and carbachol on the stimulation of inositol phosphates production was similar. However, in the rabbit retina, as opposed to the rat brain slices, carbachol had a more pronounced influence than noradrenaline in stimulating inositol phosphates production. Chick retina exposed to N-methyl-D-aspartate, quisqualate, glutamate or kainic acid resulted in cytopathological damage to cell bodies in the outer nuclear layer. The N-methyl-D-aspartate effect was nullified by memantine and MK 801 but not by kynurenic acid. In contrast the kainic acid-induced damage was specifically antagonized by kynurenic acid. The present results show that memantine influences the metabolism of inositol phosphates in neurones but not glial (Muller) cells and appears to counteract the N-methyl-D-aspartate induced cytopathological damage. How these two effects of memantine are interrelated and whether they are involved in the described beneficial therapeutic observations of memantine (as in dementia) remains to be established. PMID- 1303161 TI - Passive avoidance learning in the young chick results in time- and locus-specific elevations of alpha-tubulin immunoreactivity. AB - A monoclonal antibody was used to examine changes in immunoreactivity of the cytoskeletal protein, alpha-tubulin, following passive avoidance learning in day old chicks. Postmitochondrial fractions (16,000 g supernatants) were prepared from specific forebrain loci taken at several time points after training and assayed with the anti-alpha-tubulin antibody, YL1/2. Of the regions examined, elevations in the titre of YL1/2 were found in the left intermediate hyperstriatum ventrale 1 h, 6 h and 24 h following training, in the left lobus parolfactorius 1 h following training and in the right lobus parolfactorius 6 h and 24 h following training. No training-related changes were detected in a third forebrain region, the paleostriatum augmentatum. These results regarding the cellular dynamics of memory formation in the chick confirm and expand on earlier findings from our laboratory. PMID- 1303162 TI - Dual subcellular localization of sialidase in cultured granule cells differentiated in culture. AB - A rapid small-scale procedure was set up to obtain highly purified preparations of lysosomes and plasma membranes from the homogenate of cerebellar granule cells differentiated in culture. It consisted in a centrifugation of the postnuclear fraction P2, on a Percoll gradient with formation of an upper and lower band. The upper band, upon centrifugation on 1 M sucrose, produced a light band lying on the top, that constituted the plasma membrane preparation. The upper band constituted the lysosome preparation. The plasma membrane preparation exhibited a 6-fold relative specific activity increase of Na+, K(+)-ATPase and 5' nucleotidase, with negligible contamination by other subcellular markers; the lysosomal preparation exhibited a 30-fold relative specific activity increase of beta-galactosidase and beta-hexosaminidase, with virtually no contamination by other subcellular markers. Both the lysosome and plasma membrane preparations carried sialidase activity on MUB-NeuNAc and ganglioside GD1a. The sialidase activity on GD1a required the presence of Triton X-100 in both subcellular preparations; the sialidase activity on MUB-NeuNAc was markedly activated by albumin only in the lysosomes. The lysosomal sialidase had a unique optimal pH value, 3.9. The plasma membrane sialidase featured two values of optimal pH, one at 3.9, for both substrates and second at 5.4 and 6.0 for MUB-NeuNAc and GD1a, respectively. It is concluded that cerebellar granule cells differentiated in vitro possess one lysosomal sialidase and two plasma membrane sialidases, all of them active on ganglioside. PMID- 1303163 TI - The regulation of intracellular pH studied by 31P- and 1H-NMR spectroscopy in superfused guinea-pig cerebral cortex slices. AB - (1) The intracellular pH (pHi) of superfused slices of guinea-pig cerebral cortex was measured in 31P-NMR spectra using the chemical shifts of intracellular inorganic phosphate (Pi) and of 2-deoxyglucose 6-phosphate (DOG6P). The pHi was found to be 7.30 +/- 0.04 (SD, n = 15) in bicarbonate-buffered medium and 7.20 +/ 0.05 (n = 10, P < 0.001) in bicarbonate-free HEPES buffer of the same pH (7.4). (2) Decreases in pHe below 7.05 resulted in pHi falling to similar values, with a decrease in the energy state. There was no change in intracellular lactate as assessed by 1H-NMR. (3) The tissues showed an ability to buffer higher pH: increasing pHe to 8.0 had no effect on pHi, PCr or lactate. (4) In order to characterize possible mechanisms of pH regulation in the tissue, the recovery from acid insult was investigated under various conditions. Initially pHi was decreased to 6.44 +/- 0.15 (n = 15) by exposure to media containing 6 mM bicarbonate gassed with O2/CO2, 80:20 (pHe 6.4). When this medium was replaced by normal bicarbonate buffer (pH 7.4) there was full recovery of pHi to 7.31 +/- 0.05 (n = 15), whereas replacing the buffer with HEPES resulted in incomplete recovery of pHi to 6.88 +/- 0.15 (n = 15, P < 0.001). (5) In the presence of the carbonic anhydrase inhibitor, acetazolamide (1 mM), or the sodium/proton exchange inhibitor, amiloride (1 mM), there was an incomplete return of pHi to the control value (pHi 6.90 +/- 0.20, n = 5, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303164 TI - Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer's disease resemble embryonic development--a study of molecular forms. AB - The pattern of molecular forms of acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) separated by density gradient centrifugation was investigated in the brain and cerebrospinal fluid in Alzheimer's disease (AD), in human embryonic brain and in rat brain after experimental cholinergic deafferentation of the cerebral cortex. While a selective loss of the AChE G4 form was a rather constant finding in AD, a small but significant increase of G1 for both AChE and BChE was found in the most severely affected cases. Both in normal human brain and in AD a significant relationship could be established between the AChE G4/G1 ratio in different brain regions and the activity of choline acetyltransferase (ChAT). A similar decrease of the AChE G4 form as observed in AD can be induced in rat by experimental cholinergic deafferentation of the cerebral cortex. The increase in G1 of both AChE and BChE in different brain regions in AD is quantitatively related to the local density of neuritic plaques which are histochemically reactive for both enzymes. In human embryonic brain, a high abundance of G1 and a low G4/G1 ratio for both AChE and BChE was found resembling the pattern observed in AD. Furthermore, both in embryonic brain and in AD AChE shows no substrate inhibition which is a constant feature of the enzyme in the adult human brain. It is, therefore, concluded that the degeneration of the cholinergic cortical afferentation in AD as reflected by a decrease of AChE G4 is accompanied by the process of a neuritic sprouting response involved in plaque formation which is probably associated with the expression of a developmental form of the enzyme. PMID- 1303165 TI - GTP-binding proteins in bovine brain nuclear membranes. AB - Nuclear membranes and other subcellular fractions derived from bovine brain cortex were investigated for the existence of GTP-binding proteins. By using photolytic labeling with [alpha-32P]GTP a 29 kDa GTP-binding protein was shown to be present in nuclear membranes which was not present in the plasma membranes nor in microsomal or cytosolic fractions. Two-dimensional gel electrophoresis revealed that this protein is rather acidic with a pI lower than 4.5. Members of the heterotrimeric Gi/o family are not present in the nuclear envelope: a 39 kDa protein, ADP ribosylated by pertussis toxin, was shown to originate from plasma membrane contamination. PMID- 1303166 TI - Influence of denervation on the molecular forms of junctional and extrajunctional acetylcholinesterase in fast and slow muscles of the rat. AB - Acetylcholinesterase (AChE) molecular forms in denervated rat muscles, as revealed by velocity sedimentation in sucrose gradients, were examined from three aspects: possible differences between fast and slow muscles, response of junctional vs extrajunctional AChE, and early vs late effects of denervation. In the junctional region, the response of the asymmetric AChE forms to denervation is similar in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle: (a) specific activity of the A12 form decreases rapidly but some persists throughout and even increases after a few weeks; (b) an early and transient increase of the A4 AChE form lasting for a few weeks may be due to a block in the synthetic process of the A12 form. In the extrajunctional regions, major differences with regard to AChE regulation exist already between the normal EDL and SOL muscle. The extrajunctional asymmetric AChE forms are absent in the EDL because they became completely repressed during the first month after birth, but they persist in the SOL. Differences remain also after denervation and are, therefore, not directly due to different neural stimulation patterns in both muscles: (a) an early but transient increase of the G4 AChE occurs in the denervated EDL but not in the SOL; (b) no significant extrajunctional activity of the asymmetric AChE forms reappears in the EDL up till 7 wk after denervation. In the SOL, activity of the asymmetric AChE forms is decreased early after denervation but increases thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303167 TI - Cutaneous mechanical sensory stimulation increases extracellular acetylcholine release in cerebral cortex in anesthetized rats. AB - The effects of noxious and innocuous mechanical stimulation of various segmental skin areas (face, forelimb and paw, back, hindlimb and paw) on extracellular acetylcholine release in the cerebral cortex in the parietal lobe were examined in halothane-anesthetized rats, by means of the microdialysis technique. Pinching of a forepaw or hindpaw and brushing of a hindlimb for 10 min produced significant increases in extracellular acetylcholine release, whereas pinching of the face or back and brushing of the face, forelimb or back produced no significant changes. These results demonstrate that cutaneous sensory stimulation can regulate extracellular acetylcholine release in the cerebral cortex, and that the efficacy of the stimulation on cortical acetylcholine release is dependent on the sensory modality and the region of skin stimulated. PMID- 1303168 TI - Organization of central cholinergic neurons revealed by combined in situ hybridization histochemistry and choline-O-acetyltransferase immunocytochemistry. AB - Digoxigenin-labeled riboprobes and in situ hybridization of choline-O acetyltransferase mRNA, both alone and in combination with immunohistochemical procedures for the synthetic enzyme of acetylcholine, were used to map the topography of putative cholinergic neurons in the rat central nervous system. Only the anti-sense riboprobe yielded specific labeling, which was absent in brain sections processed with sense riboprobe. Telencephalic neurons demonstrating the mRNA for choline-O-acetyltransferase and choline-O acetyltransferase-like immunoreactivity were found in the caudate-putamen nucleus, nucleus accumbens, olfactory tubercule, Islands of Calleja complex, medial septal nucleus, vertical and horizontal limbs of the diagonal band, substantia innominata, nucleus basalis, and nucleus of the ansa lenticularis, as well as occasionally in the amygdala. Neurons in the cerebral cortex, hippocampus, and primary olfactory structures did not demonstrate hybridization signal, even though some cells in those areas were observed to exhibit choline-O acetyltransferase-like immunopositivity. Thalamic cells were devoid of hybrido- and immunoreactivity, with the exception of several neurons located primarily in the ventral two-thirds of the medial habenula. A few cell bodies labeled with riboprobe and co-localizing choline-O-acetyltransferase-like immunopositivity were found in the lateral hypothalamus, caudal extension of the internal capsule, and zona incerta. Neurons in the pedunculopontine and laterodorsal tegmental nuclei evinced moderate hybridization signal, whereas cells of the parabigeminal nucleus were very weakly reactive. In contrast, motor neurons of the cranial nerve nuclei demonstrated high levels of choline-O-acetyltransferase mRNA and choline-O-acetyltransferase-like immunoreactivity. Putative cholinergic somata in the ventral horns and intermediolateral cell columns of the spinal cord and around the central canal were also labeled with riboprobe. It is concluded that hybridocytochemistry with digoxigenin-labeled riboprobes confirms the existence of cholinergic neurons in most of the neural regions believed to contain them on the basis of acetylcholinesterase pharmacohistochemistry and choline-O acetyltransferase immunocytochemistry, with the prominent exceptions of the cerebral cortex, hippocampus, olfactory bulb, anterior olfactory nucleus, and caudal raphe nuclei, which apparently do not possess neurons expressing detectable levels of the mRNA for the synthetic enzyme of acetylcholine. PMID- 1303169 TI - In vivo activated brain astrocytes may produce and secrete nerve growth factor like molecules. AB - The cellular localization of the nerve growth factor-like immunoreactivity (NGF LIR) has been studied in the septum and hippocampus of the rat brain 7 days following partial electrolytic lesion (2 mA, 30 s) of the septohippocampal pathways or after single intraventricular administration of 15 U of interleukin-1 beta (IL-1 beta). A double immunostaining technique which allowed a simultaneous localization of NGF-LIR and that of astroglia marker glial fibrillary acidic protein was used. Our data show that after both treatments, apart from neuronal localization of NGF-LIR typical for normal brain, many astrocytes both in the septum and hippocampus became NGF-like immunoreactive. Besides, NGF-LIR often formed a "halo" reaction around astrocytes. These results support the notion that activated in vivo brain astrocytes may, just as astrocytes growing in vitro, synthesize and secrete NGF-like molecules. Our findings may be of importance in considerations concerning trophic support to the cholinergic neurons of the basal forebrain nuclei whose impaired function is essentially responsible for some cognitive deficits in neurodegenerative diseases such as Alzheimer disease. PMID- 1303170 TI - Cloning of the Huntington disease region in yeast artificial chromosomes. AB - The gene responsible for Huntington disease has been localized to a 2.5 million base pair (Mb) region between the loci D4S10 and D4S168 on the short arm of chromosome 4. As part of a strategy to clone the HD gene on the basis of its chromosomal location, we isolated genomic DNA from the HD region as a set of overlapping yeast artificial chromosome (YAC) clones. Twenty-eight YAC clones were identified by screening human YAC libraries with twelve PCR-based sequence tagged sites (STSs) from the region. We assembled the YAC clones into overlapping sets by hybridizing them to a large number of DNA probes from the HD region, including the STSs. In addition, we isolated the ends of the human DNA inserts of most of the YAC clones to assist in the construction of the contig. Although almost half of the YACs appear to contain chimeric inserts and several contain internal deletions or other rearrangements, we were able to obtain over 2.2 Mb of the HD region in YACs, including one continuous segment of 2.0 Mb covering the region that most likely contains the HD gene. Ten of the twenty eight YAC clones comprise a minimal set spanning the 2.2 Mb. These clones provide reagents for the complete characterization of this region of the genome and for the eventual isolation of the HD gene. PMID- 1303171 TI - Characterization of a YAC containing part or all of the Norrie disease locus. AB - It has been shown from pulsed-field gel electrophoresis (PFGE) that the monoamine oxidase genes A and B (MAOA & MAOB) and DXS7 loci are physically very close. We have therefore extended studies on their relationship through the characterisation of a 650 kb YAC isolated using L1.28 (recognising the DXS7 locus) as a probe. Restriction mapping of the YAC indicates that it contains both MAOA and MAOB genes in addition to the DXS7 locus. The map derived from the YL1.28-YAC is compatible both with the map from an independently derived YAC carrying MAOA and B genes and with the long range genomic map for the region. A series of subclones prepared from a 'phage library (lambda DASH II) of the YAC have been characterised and have been employed to determine the end point of the deletion of a Norrie disease (NDP) patient who has been shown to lack both DXS7 and MAO coding sequences. The pattern of retention of subclones in the deletion patient place the end point of the deletion within 30-130 kb of the proximal end of the YAC. By combining the data with established recombination analysis, we provide evidence that all or part of the NDP lies in the interval of approximately 250kb within the YAC. PMID- 1303173 TI - Both mutations in G6PD A- are necessary to produce the G6PD deficient phenotype. AB - The high prevalence of glucose 6-phosphate dehydrogenase (G6PD) deficiency in African populations is due almost entirely to the enzyme variant A-, which differs from the wild-type G6PD B by two amino acid replacements, 68 Val-->Met and 126 Asn-->Asp. The non-deficient polymorphic variant G6PD A contains only the mutation 126 Asn-->Asp. The frequencies of the G6PD A and of the G6PD A- genes in parts of Africa are both about 0.2. The 68 Val-->Met mutation has not been found in a B background. This could be because the 68 Val-->Met mutation happened to arise in an A gene in the first instance, or because the 68 Val-->Met mutation alone is not sufficient to cause G6PD deficiency. We have approached this question by producing G6PD B, A, A-, and G6PD 68 Val-->Met in a bacterial expression system and analysing their biochemical properties. With each single mutation we found a slight decrease in both the specific activity and the yield of enzyme when compared to G6PD B. When both mutations were introduced together, there was a roughly additive effect on specific activity, but a much more drastic effect on enzyme yield (4% of normal). This synergistic effect was also demonstrated on thermal stability, especially at low NADP concentrations. Comparable results were produced when the replacement 119 Gln-->Glu was studied instead of 126 Asn-->Asp. We infer that the coexistence of the two mutations is responsible for enzyme deficiency in G6PD A- because they act synergistically in causing instability of the enzyme. PMID- 1303172 TI - Screening for mutations in the open reading frame and promoter of the beta amyloid precursor protein gene in familial Alzheimer's disease: identification of a further family with APP717 Val-->Ile. AB - Following the identification of mutations in the beta-amyloid precursor protein (APP) gene in familial, early onset Alzheimer's disease (AD), we have developed a screening protocol using single strand conformation analysis (SSCA) to screen exon 17 for the known mutations within APP. In addition, we used this protocol to screen the other seventeen exons of APP and a three hundred and thirty base pair regulatory region of the promoter for new mutations in 9 families with early onset AD. Exons 16 and 17, which encode the deposited beta-amyloid peptide, were screened in a further 10 families. Our screening procedure identifies all the reported mutations within APP. While we have identified a further family with APP717 Val-->Ile, we did not find any previously undescribed mutations. Screening of other exons of APP in 2 families in which we have previously reported mutations at APP717, failed to reveal other sequence abnormalities supporting the hypothesis that the mutations at APP717 cause the disease in these families. These data suggest that mutations in APP are a rare cause of familial early onset AD (3/21 families tested) and that within APP most, possibly all, mutations which cause AD are in exon 17. PMID- 1303174 TI - Genetic linkage of the human gene for phenylethanolamine N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, to DNA markers on chromosome 17q21 q22. AB - We have determined the genetic location of the human gene encoding phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine pathway catalyzing the synthesis of epinephrine (adrenaline) from norepinephrine. This gene is linked to DNA markers on the long arm of chromosome 17, q21-q22, most closely to the DNA markers MFD15 (D17S250) (Zmax = 15.0, theta = 0.065) and fLB17.1 (Zmax = 14.6, theta = 0.045). Multipoint linkage analysis placed the PNMT locus in the interval fLB17.1-CMM86 (D17S74), at 4 centiMorgans (cM) distal to fLB17.1, and at 17 cM proximal to CMM86. Mapping of the PNMT gene will provide the basis for genetic linkage studies in families with disease which might pathogenetically involve this enzyme. The human chromosomal region 17q21-22 identified here to harbour the PNMT gene may be syntenic to the chromosomal region in the stroke-prone spontaneously hypertensive rat (SHR-SP) recently linked to blood-pressure regulation. As an increase of PNMT activity has been associated with the development of hypertension in SHR-SP, it will be of interest to perform comparative mapping of the PNMT gene. PMID- 1303175 TI - Isolation and sequence of two genes associated with a CpG island 5' of the factor VIII gene. AB - Many disease loci have been linked to the telomeric end of the long arm of the human X-chromosome, Xq28. We have isolated and sequenced cDNA sequences corresponding to two novel genes that map to Xq28. These genes, c6.1A and c6.1B, are transcribed in opposite directions from a CpG island that lies approximately 70 kilobases (kb) upstream (5') of the factor VIII locus. One of these genes, c6.1A, is highly conserved between species and expressed abundantly in many human and mouse tissues, whereas, c6.1B is moderately conserved and has a restricted tissue distribution of expression. The Xq28 gene c6.1A has an autosomal homologue that is transcriptionally inactive in B-cell lines. An open reading frame (ORF) predicting a peptide of 293 amino acids is observed for c6.1A but c6.1B does not possess a single long ORF. No striking homologies to existing genes could be found for either of the two new loci. Expressed sequences that are physically close to the factor VIII gene are candidates for disease loci that map to this region of Xq28. The relevance of these genes to disease loci was investigated using DNA and RNA from hemophilia A patients bearing deletions that extend in a 5' direction away from factor VIII. The results imply that neither of these genes are primarily responsible for the development Xq28-linked diseases. However, c6.1A and c6.1B define a region of Xq28 that is deleted in two brothers that suffer from mental handicap and dysmorphism as well as hemophilia A. Thus, this region is likely to contain loci that are important for physical and mental development. PMID- 1303176 TI - An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5' end of the monoamine oxidase A gene. AB - A CpG island has been identified just upstream of the first exon of the human monoamine oxidase A (MAOA) gene, localized to Xp11.4-Xp11.23. Southern blotting following digestion with the methylation sensitive restriction endonucleases SmaI, HpaII and HhaI, indicated that CpG dinucleotides within the CpG island were unmethylated on the active X chromosome and extensively methylated on the inactive X chromosome. These sites of differential methylation were close to a polymorphic GT-dinucleotide/VNTR region, which is located 1 kb 3' of the first exon and has a heterozygosity value of 75%. PCR primers were designed for amplification of 1.2-1.3 kb DNA fragments, encompassing both the hypervariable region and a cluster of six HpaII sites within the CpG-rich region. Cleavage of HpaII sites was found to be restricted to active X chromosomes. Therefore, following HpaII digestion, DNA fragments were exclusively amplified from inactive X chromosomes. The resulting PCR products were digested with SacI, which reduced the size of the DNA fragments containing the hypervariable region to 230-330 bp, and were subsequently analyzed on denaturating polyacrylamide gels. Because amplified fragments were exclusively derived from the inactive X chromosome, the relative densities of the two allelic fragments should reflect the proportions of cells that have either of the two X chromosome inactivated. The results of this PCR-based X chromosome inactivation assay were fully concordant with Southern blotting methylation analyses at the PGK locus. It therefore provides a rapid and informative method in tumour clonality analysis and carrier detection in X-linked diseases. PMID- 1303177 TI - Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene. AB - Hunter syndrome or mucopolysaccharidoses type II (MPS-II), is a lysosomal storage disorder caused by a deficiency in the activity of the enzyme iduronate-2 sulphatase (IDS). We have investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS-II patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations of the IDS gene were found in DNA from 9 patients two of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoint of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constitute major rearrangements of the gene. Interestingly, six of these rearrangements showed similar or identical patterns by Southern analysis suggestive for a region prone to structural alterations within the IDS gene. We also demonstrate the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. A contiguous gene deletion syndrome characterized by Hunter syndrome and epilepsy is also discussed. PMID- 1303178 TI - Sequence of the exon-containing regions of the human factor VIII gene. PMID- 1303179 TI - cA479 (D3S719): a cosmid mapped telomeric of the Von Hippel Lindau disease gene contains the D3S18 locus. PMID- 1303181 TI - A novel mutation in the p53 gene in a Burkitt's lymphoma cell line. PMID- 1303180 TI - A novel C to T substitution at nucleotide 1360 of cDNA which abolishes a natural Hha I site accounts for a new G6PD deficiency gene in Chinese. PMID- 1303182 TI - G6PD Kalyan and G6PD Kerala; two deficient variants in India caused by the same 317 Glu-->Lys mutation. PMID- 1303183 TI - Standards for reporting alleles at highly polymorphic loci: a proposal. PMID- 1303184 TI - Dinucleotide repeat polymorphisms at the DXS365, DXS443 and DXS451 loci. PMID- 1303185 TI - Microsatellite polymorphisms at the D11S554 and D11S569 loci. PMID- 1303186 TI - Dinucleotide repeat polymorphism in the Huntington's disease region at the D4S43 locus. PMID- 1303187 TI - The PAX3 gene is mapped to human chromosome 2 together with a highly informative CA dinucleotide repeat. PMID- 1303188 TI - Dinucleotide repeat polymorphism at the DXS178 locus. PMID- 1303189 TI - An Alu variable polyA repeat polymorphism upstream of L-myc at 1p32. PMID- 1303190 TI - An STS from a cDNA located in the myotonic dystrophy region (DM) on human chromosome 19q13.3. PMID- 1303191 TI - Deletions and translocations involving the distal short arm of the human X chromosome: review and hypotheses. AB - In this review we describe the various types of chromosomal abnormalities found in the distal short arm of the human X chromosome and the most common clinical features associated with each type, emphasizing the underlying molecular mechanisms. The study of these patients has significant implications for identifying the disease genes involved. PMID- 1303192 TI - A strategy for the selection of transcribed sequences in the Xq28 region. AB - As an essential step towards an exhaustive analysis of the coding potential of large regions of the genome, we have developed a protocol allowing the rapid isolation of transcripts defined by overlapping clone libraries. The method is based on the hybridisation of cDNA inserts, which had been amplified by PCR from cDNA libraries, to biotinylated DNA from cosmids or cosmid pools. Nonspecific hybrids are then removed, the selected cDNAs are eluted and reamplified by PCR. Using a cosmid containing part of the FMR-1 gene as test, we were able to demonstrate an eighty thousand fold enrichment of cDNAs for this gene after two rounds of selection-amplification. The technique was applied to the analysis of transcripts from two cosmid contigs, together encompassing a region of 900 kb in Xq28. These experiments have thus far resulted in the identification of 81 cDNA clones, of which 54 clones were mapped back to the cosmid contigs. Of the 54 clones placed on the contig maps, 12 cDNA clones can be shown to belong to two genes which have been previously reported (L1CAM and QM). PMID- 1303193 TI - A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. AB - Waardenburg syndrome type 1 (WS1) is an autosomal dominant disorder characterized by deafness, dystopia canthorum, heterochromia iridis, white forelock, and premature greying. A similar phenotype is caused in the mouse by mutations in the Pax-3 gene. This observation, together with comparisons of conserved syntenies in the murine and human genetic maps, suggested that at least some WS1 mutations should occur in HuP2, the probable human homolog of Pax-3. Two mutations in the HuP2 sequence of individuals with WS1 have been reported recently. Both of them occur in the highly conserved paired box region of the gene, which encodes a DNA binding domain. The functional consequences of these mutations are at present speculative. We report here a 14 bp deletion in the paired domain encoded by exon 2 of HuP2 in an Indonesian family segregating for WS1. This frameshift mutation results in a premature termination codon in exon 3. The HuP2 product is a truncated protein lacking most of the paired domain and all of the predicted homeo domain. We propose that the WS1 phenotype in this family is due to loss of function of HuP2 and discuss two mechanisms for the dominant effect of this mutation. PMID- 1303194 TI - Genetic and physical mapping of the Treacher Collins syndrome locus: refinement of the localization to chromosome 5q32-33.2. AB - Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development, the locus for which has been chromosomally localized to 5q31-34. We have isolated four hypervariable microsatellite markers (heterozygosity values range from 0.70 to 0.89) which have been mapped to distal 5q. Fifteen unrelated TCOF1 families have been analyzed for linkage to these markers. There is strong evidence demonstrating linkage to all of these markers; the strongest support for positive linkage being provided by the marker IG52, with a maximum pairwise lod score of 9.77 at a recombination fraction of 0.055. Analysis of recombinant individuals, physical mapping by fluorescence in situ hybridization and genetic linkage analysis demonstrated that the TCOF1 locus was flanked proximally by the loci 2C7 and 2D10, and distally by the loci IG26 and IG52 with a maximum lod score of 14.4, as assessed by multipoint linkage analysis. The refinement of the localization of the TCOF1 locus to 5q32-33.2, with flanking markers, represents an important step towards the identification of the mutated gene itself. PMID- 1303196 TI - Constraints acting on the exon positions of the splice site sequences and local amino acid composition of the protein. AB - The exon positions located at the 5' and 3' splice sites are involved in two functions: in the accurate removal of introns from the nuclear pre-messenger RNAs and in coding for amino acids. Therefore, at least two constraints will act on the exon positions: the splicing constraint and the protein constraint. In the present study we investigate the effect of those constraints on a set of splice sites extracted from GenBank. The consensus matrices computed for each intron location in the reading frame present striking differences at the exon positions of the 5' splice sites. The results obtained can not be explained by the action of a single constraint but rather by the competition between the splicing and protein constraints. Out of eight sites corresponding to codons located in the vicinity of the intron, three present an amino acid distribution that differs greatly from the average amino acid composition of the proteins. Each of these three sites can be characterized by specific amino acids. Results show that the splicing constraint has an effect on the local amino acid composition of the protein as long as the function of the protein is not disrupted. PMID- 1303195 TI - Moderate instability of the trinucleotide repeat in spino bulbar muscular atrophy. AB - Increased length of a protein-coding CAG repeat within the androgen receptor gene appears to be the only type of mutation responsible for spino-bulbal muscular atrophy (SBMA or Kennedy disease). We have analysed a large 4-generation SBMA family and found that the mutant allele was unstable upon transmission from parent to child, with a documented variation from 46 to 53 repeats and a tendency to increase in size (7 increases and a single decrease in 17 events), which appeared stronger upon transmission from a male than from a female. Our results suggest also limited somatic instability of the abnormal allele, with observable variation of up to 2-3 repeats. This indicates that the behavior of the CAG repeat is similar to that observed for small premutations in the fragile X syndrome, or small abnormal alleles in myotonic dystrophy, two diseases which are caused by expansion of an unstable trinucleotide repeat. PMID- 1303197 TI - Identification and characterization of a new gene in the human Xq28 region. AB - A human Xqter chromosome cosmid library was screened with a mixed probe derived from porcine kidney mRNA. A new expressed gene was identified in a cosmid clone known to be part of a G6PD cosmid contig. This gene is most likely a housekeeping gene because the cDNA clone recognizes a 1 kb mRNA transcript in all cell lines and tissues tested. Hybridizing genomic DNA of several species with a cDNA probe indicated that the gene is highly conserved during evolution and that it belongs to a gene family. The genomic sequence shows a 100% homology with the recently identified QM cDNA sequence. PMID- 1303198 TI - An archipelago of CpG islands in Xq28: identification and fine mapping of 20 new CpG islands of the human X chromosome. AB - 19 probes for CpG islands, mapping to Xq28, have been used as probes to construct a physical map of genes of this band of the human X chromosome. A total of 22 CpG islands have been precisely mapped in respect to known loci along the 9-10 Mb of Xq28. The fine mapping of such a large number of CpG islands has demonstrated that also in gene rich Giemsa light bands, like Xq28, gene distribution is non uniform: the CpG islands are clustered in the distal portion of the band in a 2 Mb region between the G6PD gene and the DXS15 locus. Moreover, 16 CpG islands were found between the G6PD and the RCP/GCP genes, a region of DNA of only about 300 kb. If this structural organization has a biological function it has yet to be determined. However, the isolation of large genomic regions enriched in gene sequences and the availability of cosmid or YAC contigs will provide the means to test the significance of such gene organization, as well as the material for large sequencing projects and gene search, for the identification of candidate genes for inherited disorders mapped to Xq28 and for comparative mapping. PMID- 1303199 TI - A further tetranucleotide repeat polymorphism in the vWF gene. PMID- 1303200 TI - Dinucleotide repeat polymorphism at the human erythroid alpha-spectrin (SPTA1) mRNA gene detected using PCR. PMID- 1303201 TI - Dinucleotide repeat polymorphism at the D18S37 locus. PMID- 1303202 TI - Dinucleotide repeat polymorphism at the D21S236 locus. PMID- 1303203 TI - Dinucleotide repeat polymorphism at the D3S1229 locus. PMID- 1303204 TI - Dinucleotide repeat polymorphism at the D5S356 locus. PMID- 1303205 TI - The 'colorizing' of cytogenetics: is it ready for prime time? PMID- 1303206 TI - Multicolor fluorescence in situ hybridization for the simultaneous detection of probe sets for chromosomes 13, 18, 21, X and Y in uncultured amniotic fluid cells. AB - The most frequent aneuploidies in newborns involve the autosomes 13, 18 and 21 as well as both sex chromosomes. Fluorescence in situ hybridization readily allows the detection of numerical chromosomal aberrations throughout all stages of the cell cycle. Using a multicolor fluorescence in situ hybridization approach based on combinatorial probe labeling and digital imaging microscopy we demonstrate the simultaneous visualization of probe sets specific for chromosomes 13, 18, 21, X and Y. This approach enables one to evaluate aberrations of multiple chromosomes in a single hybridization experiment using metaphase chromosomes and interphase nuclei from a variety of cell types, including lymphocytes and amniocytes. PMID- 1303207 TI - Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I. AB - We described cloning and characterization of an inversion breakpoint of chromosome 2 inv(2)(q35q37.3) observed in a patient with Waardenburg syndrome type I (WSI). Genomic cosmid clones containing the HuP2 gene, which was considered as a candidate for WSI, were isolated from a library constructed from the patient DNA. One of the clones contained the inversion breakpoint and revealed signals at both 2q35 and 2q37 by fluorescent in situ hybridization (FISH), indicating disruption of the HuP2 gene by the inversion. Our result further supports that the HuP2 gene is a candidate for Waardenburg syndrome type I and is located at q35. PMID- 1303208 TI - Isolation of human minisatellite loci detected by synthetic tandem repeat probes: direct comparison with cloned DNA fingerprinting probes. AB - As a direct comparison with cloned 'DNA fingerprinting' probes, we present the results of screening an ordered array Charomid library for hypervariable human loci using synthetic tandem repeat (STR) probes. By recording the coordinates of positive hybridization signals, the subset of clones within the library detected by each STR probe can be defined, and directly compared with the set of clones detected by naturally occurring (cloned) DNA fingerprinting probes. The STR probes vary in the efficiency of detection of polymorphic minisatellite loci; among the more efficient probes, there is a strong overlap with the sets of clones detected by the DNA fingerprinting probes. Four new polymorphic loci were detected by one or more of the STR probes but not by any of the naturally occurring repeats. Sequence comparisons with the probe(s) used to detect the locus suggest that a relatively poor match, for example 10 out of 14 bases in a limited region of each repeat, is sufficient for the positive detection of tandem repeats in a clone in this type of library screening by hybridization. These results not only provide a detailed evaluation of the usefulness of STR probes in the isolation of highly variable loci, but also suggest strategies for the use of these multi-locus probes in screening libraries for clones from hypervariable loci. PMID- 1303209 TI - D20S19, linked to low voltage EEG, benign neonatal convulsions, and Fanconi anaemia, maps to a region of enhanced recombination and is localized between CpG islands. AB - Recent linkage studies located genes responsible for the low voltage EEG, benign neonatal convulsions and for the Fanconi anaemia to the vicinity of the VNTR marker CMM6 (D20S19). Physical mapping experiments using pulsefield electrophoresis in the distal part of chromosome 20q were chosen as a first step towards cloning of these genes. The observed pattern of shared fragments lead to the locus order 'tel-IP20K09-RMR6-CMM6-MS214-cen', which differs from previously reported genetic linkage maps. The physical intervals between these probes are markedly shorter compared with the genetic distances. Clusters of rare cutter sites around CMM6 point to at least four closely related CpG islands. PMID- 1303210 TI - Isolation and mapping to 17p12-13 of the human homologous of the murine growth arrest specific Gas-3 gene. AB - A family of growth arrest specific (Gas) genes was operationally defined on the basis of the strategy utilized to isolate them e.g. differential expression in quiescent and growing cells. Our interest in the Gas-3 gene was prompted by our previously reported localization of the gene on the mouse chromosome 11.44 +/- 1.9 cM proximal to the Trp53 locus and by the finding, by others, that it codes for a myelin protein and that a point mutation in its fourth putative transmembrane region is associated with the trembler mutation. We have isolated the human homologous of the mouse Gas-3 gene and utilized the cloned sequences as a probe to localize the gene on human chromosomes both by analysis of human rodent somatic cell hybrids and in situ hybridization of human metaphases. We have now localized the human Gas-3 gene on chromosome 17p12-13. Its possible role in both the development of neoplasia in neurofibromatosis patients and in the myelin degenerative disease as the Charcot-Marie-Tooth is discussed. PMID- 1303211 TI - Mutation analysis of the iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II (Hunter syndrome). AB - Iduronate-2-sulfatase (IDS) cDNA from fibroblasts of nine patients with Hunter syndrome (mucopolysaccharidosis type II) was screened for mutations using single strand conformation polymorphism analysis. Direct sequencing revealed a number of different mutations including missense or nonsense point mutations, deletions of one, two, or 60 base pairs, and a 22 base pair-insertion. Mutations of these types probably account for most IDS gene defects as only about 20% of Hunter patients have a complete deletion or gross structural alteration of their IDS gene. Thus the broad clinical variability amongst the Hunter patients may be due to the extensive genetic heterogeneity seen. The relationship between genotype and clinical phenotype is analysed in 12 Hunter patients. PMID- 1303212 TI - Detection of ABO blood group polymorphism by denaturing gradient gel electrophoresis. AB - We report the use of a polymerase chain reaction (PCR) format together with denaturing gradient gel electrophoresis (DGGE) which allows rapid identification of the 6 major genotypes (AA, AO, BB, BO, AB and OO) of the human ABO blood group polymorphism in a single amplification. The procedure also distinguishes hitherto undescribed polymorphisms associated with the O and B alleles. Thus in testing 95 unrelated European individuals 4 different O alleles, 2 B alleles and 1 A allele were identified by DGGE and the level of recognisable heterozygosity, and hence the information content of the locus as a genetic marker, was raised from 3/95 (3%) to 66/95 (70%). The procedure is robust, genotyping is rapid and clear-cut, and has immediate implications for the use of the ABO locus in linkage analysis on chromosome 9q, the investigation of disease associations and forensic identification. PMID- 1303213 TI - A 3' consensus splice mutation in the human dystrophin gene detected by a screening for intra-exonic deletions. PMID- 1303214 TI - Improving the polymorphism content of the 3' UTR of the human IGF2R gene. PMID- 1303215 TI - Dinucleotide repeat polymorphism at the D4S251 locus. PMID- 1303216 TI - Dinucleotide repeat polymorphism at the D21S65 locus. PMID- 1303217 TI - Additional polymorphism at a CHR 9 reference locus (D9S12). PMID- 1303218 TI - Dinucleotide repeat polymorphism at the human gene for the brain-derived neurotrophic factor (BDNF). PMID- 1303219 TI - Dinucleotide repeat polymorphism in the human estrogen receptor (ESR) gene. PMID- 1303220 TI - Canine lessons for human lupus. PMID- 1303221 TI - Systemic lupus erythematosus in males: analysis of clinical and laboratory features. AB - We analysed the clinical and laboratory features of 16 males in comparison with 231 females from a series of 247 unselected patients with systemic lupus erythematosus (SLE). There was no significant difference between male and female patients with regard to age at onset and age at diagnosis. Apart from serositis, which was found to occur at a significantly higher frequency in male patients, the incidence of clinical features at disease onset was similar in both sexes. Analysis of clinical findings during the evolution of the disease showed no significant difference between male and female patients. Similarly, no significant immunological difference was found between the two groups. Thus, except for a higher frequency of serositis as the presenting symptom in males, we could not find any notable differences in clinical and serological parameters of male and female patients with SLE. PMID- 1303222 TI - Antibodies against gangliosides in patients with SLE and neurological manifestations. AB - Pathogenesis of neuropsychiatric manifestations of systemic lupus erythematosus (SLE) has not been clearly defined, and the search for pathogenic mechanisms has focused on the importance of several autoantibodies. There is increasing evidence that antibodies against gangliosides may have a pathogenic role in some neurological disorders. The aim of the present study was to examine the association between antibodies against gangliosides and neuropsychiatric SLE. We found anti-type II ganglioside antibodies in two out of 32 patients with multiple sclerosis (6.25%) and in 10 out of 60 patients with SLE (16.6%); five of 17 patients with neurological abnormalities also had high levels of these antibodies (29.4%). Five of the 10 patients with SLE and positive antiganglioside antibody had only IgM antibodies, three had IgG antibodies and two had both isotypes. By chi-square analysis, the incidence of anti-type II ganglioside antibodies was not significantly higher in patients with symptoms related to the nervous system than in SLE patients without neurological involvement (P > 0.2). No clear correlation was found between antibodies against gangliosides and cardiolipin. PMID- 1303223 TI - Vitamin E and discoid lupus erythematosus. AB - We treated seven patients with discoid lupus erythematosus (DLE) with Vitamin E in an oral dose of 400 mg three times per day for 12 weeks. All other systemic and topical treatments were discontinued 1 month before initiation of the trial. The drug was then stopped and follow-up continued for at least another 4 weeks. No patient showed clearing of lesions. The trial was conducted during summer, when DLE is likely to be most active. There was no deterioration in any patient. No side effects were noted. PMID- 1303225 TI - Pioneer proteins. PMID- 1303224 TI - Dose response in Charcot-Marie-Tooth disease. PMID- 1303226 TI - Retinal genetics: a nullifying effect for rhodopsin. PMID- 1303227 TI - Clinical conundrums in fragile X syndrome. PMID- 1303228 TI - The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot Marie-Tooth disease type 1A. AB - Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a large DNA duplication on the short arm of human chromosome 17. The trembler (Tr) mouse serves as a model for CMT1A because of phenotypic similarities and because the Tr locus maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17. Recently, the peripheral myelin gene Pmp-22 was found to carry a point mutation in Tr mice. We have isolated cDNA and genomic clones for human PMP-22. The gene maps to human chromosome 17p11.2-17p12, is expressed at high levels in peripheral nervous tissue and is duplicated, but not disrupted, in CMT1A patients. Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A. PMID- 1303229 TI - The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. AB - Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a DNA duplication at chromosome 17p11.2. In view of the point mutation in the gene for peripheral myelin protein pmp-22/gas-3 in Trembler mice, a murine model for CMT1A, we have analysed whether this gene is altered in CMT1A. Here we show that the human homologue of the murine pmp-22 gene is located within the CMT1A DNA duplication, which is a direct repeat and does not interrupt the coding region of PMP-22. Expression of PMP-22 in CMT1A fibroblasts is similar to expression in control fibroblasts. Increased gene dosage or altered PMP-22 expression in the peripheral nervous system are therefore possible mechanisms by which PMP-22 is involved in CMT1A. PMID- 1303230 TI - The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie Tooth disease type 1A duplication. AB - Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy. PMID- 1303231 TI - Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A. AB - Charcot-Marie-Tooth disease 1A (CMT1A) is a hereditary demyelinating peripheral neuropathy, associated with a DNA duplication on chromosome 17p11.2. A related disorder in the mouse, trembler (Tr), maps to mouse chromosome 11 which has syntenic homology to human chromosome 17p. Recently, the peripheral myelin protein-22 (pmp-22) gene was identified as the likely Tr locus. We have constructed a partial yeast artificial chromosome contig spanning the CMT1A gene region and mapped the PMP-22 gene to the duplicated region. These observations further implicate PMP-22 as a candidate gene for CMT1A, and suggest that over expression of this gene may be one mechanism that produces the CMT1A phenotype. PMID- 1303232 TI - Characterization of a yeast artificial chromosome contig spanning the Huntington's disease gene candidate region. AB - The Huntington's disease (HD) gene has been localized by recombination events to a region covering 2.2 megabases (Mb) DNA within chromosome 4p16.3. We have screened three yeast artificial chromosome (YAC) libraries in order to isolate and characterize 44 YAC clones mapping to this region. Approximately 50% of the YACs were chimaeric. Unstable YACs were identified across the whole region, but were particularly prevalent around the D4S183 and D4S43 loci. The YACs have been assembled into a contig extending from D4S126 to D4S98 covering roughly 2 Mb DNA, except for a gap of about 250 kilobases (kb). The establishment of a YAC contig which spans the region most likely to contain the HD mutation is an essential step in the isolation of the HD gene. PMID- 1303233 TI - Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. AB - The myotonic dystrophy (DM) mutation has recently been identified as an unstable trinucleotide CTG repeat which is present 5-30 times in the normal population but which is amplified up to 2,000 times in DM. We have determined the status of the CTG repeat in 272 DM individuals. Infants with severe congenital DM, as well as their mothers, are shown to have on average a greater amplification of the CTG repeat than is seen in the noncongenital DM population. This fact, when viewed in conjunction with the tendency to increased CTG repeat length in our DM kindreds, provides evidence for the existence of genetic anticipation in the transmission of DM. PMID- 1303234 TI - Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9. AB - Fanconi anaemia (FA) is a DNA repair disorder characterized by cellular hypersensitivity to DNA cross-linking agents and extensive phenotypic heterogeneity. To determine the extent of genetic heterogeneity present in FA, a panel of somatic cell hybrids was constructed using polyethylene glycol-mediated cell fusion. Three new complementation groups were identified, designated FA(B), FA(C) and FA(D), and the gene defective in FA(C) which we have recently cloned was localized to chromosome 9q22.3 through in situ hybridization. These results suggest that mutations in at least four different genes lead to FA, a degree of genetic heterogeneity comparable to that of other DNA repair disorders. PMID- 1303235 TI - Isolation of a candidate gene for Norrie disease by positional cloning. AB - The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein. PMID- 1303236 TI - Isolation and characterization of a candidate gene for Norrie disease. AB - Previous analysis has refined the location of the gene for Norrie disease, a severe, X-linked, recessive neurodevelopmental disorder, to a yeast artificial chromosome subfragment of 160 kilobases (kb). This fragment was used to screen cDNA libraries from human fetal and adult retina. As a result, we have identified an evolutionarily conserved cDNA, which is expressed in fetal and adult brain and encodes a predicted protein of 133 amino acids. The cDNA detects genomic sequences which span a maximum of 50 kb, and which are partly deleted in several typical Norrie disease patients. An EcoRI polymorphism with a calculated heterozygosity value of 43% was observed. The locus identified is a strong candidate for the Norrie disease gene. PMID- 1303237 TI - A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa. AB - Mutations within the rhodopsin gene are known to give rise to autosomal dominant retinitis pigmentosa (RP), a common hereditary form of retinal degeneration. We now describe a patient with autosomal recessive RP who is homozygous for a nonsense mutation at codon 249 within exon 4 of the rhodopsin gene. This null mutation, the first gene defect identified in autosomal recessive retinitis pigmentosa, should result in a functionally inactive rhodopsin protein that is missing the sixth and seventh transmembrane domains including the 11-cis-retinal attachment site. We also found a different null mutation carried heterozygously by an unrelated unaffected individual. Heterozygous carriers of either mutation had normal ophthalmologic examinations but their electroretinograms revealed an abnormality in rod photoreceptor function. PMID- 1303238 TI - Evidence for a relationship between Ehlers-Danlos type VII C in humans and bovine dermatosparaxis. AB - Ehlers-Danlos (ED) syndrome type VII is characterized by the accumulation of collagen precursors in connective tissues. ED VII A and B are caused by mutations in the genes of alpha 1 and alpha 2 collagen I which result in the disruption of the cleavage site of procollagen I N-proteinase. The existence of ED VII C in humans has been hypothesized on the basis of a disorder in cattle and sheep related to the absence of the enzyme. We now present evidence for the existence of this disease in humans, characterized by skin fragility, altered polymers seen as hieroglyphic pictures with electron microscopy, accumulation of p-N-alpha 1 and p-N-alpha 2 collagen type I in the dermis and absence of processing of the p N-I polypeptides in fibroblast cultures. PMID- 1303239 TI - Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. AB - Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with presenile dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, presenile dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene. PMID- 1303240 TI - Isolation of chromosome 21-specific yeast artificial chromosomes from a total human genome library. AB - A new approach for the isolation of chromosome-specific subsets from a human genomic yeast artificial chromosome (YAC) library is described. It is based on the hybridization with an Alu polymerase chain reaction (PCR) probe. We screened a 1.5 genome equivalent YAC library of megabase insert size with Alu PCR products amplified from hybrid cell lines containing human chromosome 21, and identified a subset of 63 clones representative of this chromosome. The majority of clones were assigned to chromosome 21 by the presence of specific STSs and in situ hybridization. Twenty-nine of 36 STSs that we tested were detected in the subset, and a contig spanning 20 centimorgans in the genetic map and containing 8 STSs in 4 YACs was identified. The proposed approach can greatly speed efforts to construct physical maps of the human genome. PMID- 1303241 TI - Light is a dominant mouse mutation resulting in premature cell death. AB - Light is a dominant mutant allele of the mouse brown locus which results in hairs pigmented only at their tips. The phenotype is due to premature melanocyte death. We have sequenced the tyrosinase-related protein-1 cDNA encoded at this locus from Light mice and found that it contains a single base alteration from wild type, causing an Arg to Cys change in the protein. To further elucidate the mutant phenotype, we studied the expression of melanocyte specific genes in the skin of Light mice. We have demonstrated premature melanocyte death, but only in pigmented mice, indicating that the cell death is mediated through the inherent cytotoxicity of pigment production. PMID- 1303242 TI - Signs of an imprinted domain. PMID- 1303243 TI - Origin of human chromosome 2. PMID- 1303244 TI - Schizophrenia scepticism. PMID- 1303245 TI - Molecular evolution of the human interleukin-8 receptor gene cluster. AB - Interleukin-8 (IL-8) is the prototype for a family of at least eight neutrophil chemoattractants whose genes map to human chromosome 4q13-q21. Two human IL-8 receptors, IL8RA and IL8RB, are known from cDNA cloning; IL8RA is a promiscuous receptor for at least two other related ligands, GRO alpha and NAP-2. We now report cloning of the genes for IL8RA, IL8RB and a recently inactivated pseudogene of receptor A (IL8RAP). These form a cluster of only three genes in the superfamily of G protein-coupled receptors (GPCRs) and map to 2q34-q35. The coevolutionary diversity displayed by the IL-8 ligand-receptor complex--ligand promiscuity for IL-8, receptor promiscuity for IL8RA, gene duplication for both ligands and receptors and gene extinction in the case of IL8RAP--is unprecedented for the GPCR superfamily. PMID- 1303246 TI - Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. AB - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of unknown aetiology that affects numerous body systems including skin, brain and kidneys. Some TSC has been linked to chromosome 9, additional TSC genes on chromosomes 11 and 12 have been proposed, but the majority of TSC families remain unlinked. Using TSC families in which data had excluded linkage to chromosome 9, we failed to detect linkage with loci on chromosomes 11, 12 and others. One marker examined was D16S283, the closest locus on the proximal side of the polycystic kidney disease type 1 (PKD1) gene. Linkage between TSC and D16S283 demonstrated a lod score of 9.50 at theta = 0.02 with one family independently presenting a lod score of 4.44 at theta = 0.05. These data reveal an important TSC locus near the region of PKD1 on chromosome 16p13. PMID- 1303247 TI - A frameshift mutation in the gamma E-crystallin gene of the Elo mouse. AB - The murine Elo (eye lens obsolescence) mutation confers a dominant phenotype characterized by malformation of the eye lens. The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster. We have analysed the sequence of this gene from the Elo mouse and identified a single nucleotide deletion which destroys the fourth and last "Greek key" motif of the protein. This mutation is tightly associated with the phenotype, as no recombination was detected in 274 meioses. In addition, the mutant mRNA is present in the affected lens, providing further support for our hypothesis that the deletion is responsible for the dominant Elo phenotype. PMID- 1303248 TI - Linkage of Rieger syndrome to the region of the epidermal growth factor gene on chromosome 4. AB - Rieger syndrome is an autosomal dominant disorder of morphogenesis in which previous cytogenetic arrangements have suggested chromosome 4 as a candidate chromosome. Using a group of highly polymorphic short tandem repeat polymorphisms (STRP), including a new tetranucleotide repeat for epidermal growth factor (EGF), significant linkage of Rieger syndrome to 4q markers has been identified. Tight linkage to EGF supports its role as a candidate gene, although a recombinant in an unaffected individual has been identified. This study demonstrates the utility of using polymorphic STRP markers when only a limited number of small families are available for study. PMID- 1303249 TI - Traces of her workings. PMID- 1303250 TI - Distinct and overlapping functions of allelic forms of human mannose binding protein. AB - Human mannose binding protein (MBP) is a C-type serum lectin involved in first line host defense against a variety of bacterial, fungal and viral pathogens. Recently an association was found between low levels of serum MBP and an increased frequency of recurrent infections in infants. A particular genotype, in which glycine is substituted by aspartic acid at codon 54 of MBP in the fifth collagen repeat, shows apparent concordance with the clinical phenotype. We report, however, that this genotype occurs in 5% of the population and encodes a functional protein. Our results indicate that the Gly54Asp allele does not account for a deficiency state, but instead suggest that MBP may have two predominant allelic forms that have overlapping function and differ only in their ability to activate the classical pathway of complement. PMID- 1303251 TI - Genetic dissection of autoimmune type I diabetes in the BB rat. AB - The BB rat is among the best models of insulin-dependent diabetes mellitus--with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T-cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, which is tightly linked to the neuropeptide Y (Npy) gene on chromosome 4, a gene linked to the major histocompatibility complex (MHC) on chromosome 20, and a third unmapped gene for which the Fischer rat strain carries an allele conferring resistance. PMID- 1303252 TI - Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2. AB - Parental imprinting is a phenomenon in mammals whereby the maternal and paternal alleles of a gene are differentially expressed. Three murine genes have been shown to display this type of allele-specific expression. Two of them, insulin like growth factor-2 (Igf-2) and H19, map to the distal end of mouse chromosome 7, but are imprinted in opposite directions. Pulsed-field gel electrophoresis and large-fragment DNA cloning were utilized to establish a physical map that includes H19 and Igf-2. Igf-2 lies approximately 90 kilobases of DNA 5' to H19, in the same transcriptional orientation. This physical proximity is conserved in humans, based on pulsed-field gel analysis. We conclude that H19 and Igf-2 constitute an imprinted domain. PMID- 1303253 TI - Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase. AB - Patients with glucocorticoid-remediable aldosteronism (GRA) from 12 kindreds possess chimaeric gene duplications arising from unequal crossing-over, fusing regulatory sequences of steroid 11 beta-hydroxylase to coding sequences of aldosterone synthase. These chimaeric genes are specific for GRA and explain the biochemistry, physiology and genetics of this form of hypertension. Sites of crossing over range from intron 2 to intron 4. Most mutations have arisen independently from either sister or non-sister chromatid exchange between these genes, which are only 45 kilobases apart. The possibility of a susceptibility allele for GRA of Irish origin is suggested. These findings indicate the utility of a direct genetic test for this disorder. PMID- 1303254 TI - Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1. AB - Splotch is considered a model of Waardenburg syndrome type I (WSI) because the abnormalities are caused by mutations in homologous genes, Pax-3 in mice and PAX3 (HuP2) in humans. We examined inner ear structure and function in Splotch mutants (Sp/+) and found no sign of auditory defects, in contrast to the deafness in many WSI individuals. The difference in expression of the genes in the two species may be due to different parts of the gene being mutated, or may result from variations in modifying influences as yet undefined. PMID- 1303255 TI - Bouncing off microsatellites. PMID- 1303256 TI - Isolation of a candidate gene for Norrie disease by positional cloning. PMID- 1303257 TI - Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus. AB - X-linked nephrogenic diabetes insipidus (NDI) is a rare disorder in which the kidney is insensitive to the antidiuretic hormone, vasopressin. It has been proposed that the kidney-specific V2 vasopressin receptor, a G protein-coupled receptor, is defective in this disorder as both the disease and the receptor map to Xq28. We report six unique mutations in the V2 receptor gene of five unrelated NDI patients, with one patient having two mutations. The most severely affected patient has a nonsense mutation which would terminate the protein in transmembrane domain III. Other mutations include three missense mutations, a frameshift and one small in-frame deletion. These results represent one of the first examples of recessive mutations affecting a G protein-coupled receptor. PMID- 1303258 TI - Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X linked hydrocephalus. AB - A locus for X-linked hydrocephalus (HSAS), which is characterized by mental retardation and enlarged brain ventricles, maps to the same subchromosomal region (Xq28) as the gene for neural cell adhesion molecule L1. We have found novel L1 mRNA species in cells from affected members of a HSAS family containing deletions and insertions produced by the utilization of alternative 3' splice sites. A point mutation at a potential branch point signal in an intron segregates with the disease and is likely to be responsible for the abnormal RNA processing. These results suggest that HSAS is a disorder of neuronal cell migration due to disruption of L1 protein function. PMID- 1303259 TI - A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. AB - Some acute lymphocytic leukaemias, particularly those in young children, are associated with a t(4;11)(q21;q23) reciprocal translocation. We have cloned the translocation breakpoint on chromosome 11q23 and isolated corresponding RNA transcripts from this region. The translocation occurs within a cluster of Alu repetitive elements located within an intron of a gene that gives rise to 11.5 (kb) transcript spanning the translocation breakpoint. The 11.5 kb transcript encodes a protein that is highly homologous to the Drosophila trithorax gene, a developmental regulator. An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region. PMID- 1303261 TI - Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. AB - A predisposing gene for breast and ovarian cancer has recently been mapped to chromosome 17q12-21. If this gene is a tumour suppressor gene, allele losses would be expected in the tumours of affected family members and the losses should affect the wild-type chromosome, reflecting the need for inactivation of the wild type allele at the predisposing locus. In four multiple case breast-ovarian cancer families, we have found that in each of nine tumours which showed allele losses, the losses were from the wild-type chromosome. This suggests that the putative 'breast-ovarian' cancer gene is indeed a tumour suppressor gene. PMID- 1303260 TI - Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. AB - Notch and the m9/10 gene (groucho) of the Enhancer of split (E(spI)) complex are members of the "Notch group" of genes, which is required for a variety of cell fate choices in Drosophila. We have characterized human cDNA clones encoding a family of proteins, designated TLE, that are homologous to the E(spI) m9/10 gene product, as well as a novel Notch-related protein. The TLE genes are differentially expressed and encode nuclear proteins, consistent with the presence of sequence motifs associated with nuclear functions. The structural redundancy implied by the existence of more than one TLE and Notch-homologous gene may be a feature of the human counterparts of the developmentally important Drosophila Notch group genes. PMID- 1303262 TI - A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. AB - Breast cancer in men is rare--among the risk factors that have been identified are a family history of breast cancer and evidence of androgen insufficiency. We report a family in which two brothers who both developed breast cancer had clinical and endocrinological evidence of androgen resistance. Sequence analysis revealed a mutation in the androgen receptor gene on the X chromosome, within the region encoding the DNA binding domain. This is the first report of a germline mutation in a member of the steroid/thyroid hormone receptor superfamily associated with the development of cancer. PMID- 1303263 TI - Identifying individuals by sequencing mitochondrial DNA from teeth. AB - Mitochondrial DNA (mtDNA) was extracted from teeth stored from 3 months to 20 years, including teeth from the semi-skeletonized remains of a murder victim which had been buried for 10 months. Tooth donors and/or their maternal relatives provided blood or buccal cells, from which mtDNA was also extracted. Enzymatic amplification and direct sequencing of roughly 650 nucleotides from two highly polymorphic regions of mtDNA yielded identical sequences for each comparison of tooth and fresh DNA. Our results suggest that teeth provide an excellent source for high molecular weight mtDNA that can be valuable for extending the time in which decomposed human remains can be genetically identified. PMID- 1303264 TI - Norrie disease is caused by mutations in an extracellular protein resembling C terminal globular domain of mucins. AB - A candidate gene for Norrie disease, an X-linked disorder characterized by blindness, deafness and mental disturbances, was recently isolated and found to contain microdeletions in numerous patients. No strong homologies were identified. By studying the number and spacing of cysteine residues, we now detect homologies between the Norrie gene product and a C-terminal domain which is common to a group of proteins including mucins. Three newly-characterized missense mutations, replacing evolutionarily conserved cysteines or creating new cysteine codons, emphasize the functional importance of these sites. These findings and the clinical features of this disorder suggest a possible role for the Norrie gene in neuroectodermal cell-cell interaction. PMID- 1303266 TI - Methylation of CpG sites of two X-linked genes coincides with X-inactivation in the female mouse embryo but not in the germ line. AB - To further our understanding of initiation and imprinting of X-chromosome inactivation, we have examined methylation of specific CpG sites of X-linked Pgk 1 and G6pd genes throughout female mouse development. Methylation occurs around the time of inactivation and earlier for Pgk-1, which is closer to the X inactivation centre. In female primordial germ cells, the inactive X chromosome escapes methylation; this may underly the reversibility of inactivation at meiosis. Similarly, the genes are unmethylated on the inactive X chromosome in sperm; hence, the imprint specifying preferential X-inactivation in extra embryonic tissues must reside elsewhere. PMID- 1303265 TI - Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes. AB - We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes. PMID- 1303267 TI - Keeping track of the translocations. PMID- 1303268 TI - Breast cancer genes: how many, where and who are they? PMID- 1303269 TI - A common origin for cornified envelope proteins? PMID- 1303270 TI - A brief history of gene therapy. AB - The concepts of gene therapy arose initially during the 1960s and early 1970s whilst the development of genetically marked cells lines and the clarification of mechanisms of cell transformation by the papaovaviruses polyoma and SV40 was in progress. With the arrival of recombinant DNA techniques, cloned genes became available and were used to demonstrate that foreign genes could indeed correct genetic defects and disease phenotypes in mammalian cells in vitro. Efficient retroviral vectors and other gene transfer methods have permitted convincing demonstrations of efficient phenotype correction in vitro and in vivo, now making gene therapy a broadly accepted approach to therapy and justifying clinically applied studies with human patients. PMID- 1303272 TI - Three of a kind. PMID- 1303271 TI - Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. AB - Nephrogenic diabetes insipidus (DIR) is an X-linked disorder characterized by insensitivity of the distal nephron for the pituitary hormone, vasopressin. The genetic map location of the DIR gene on chromosome Xq28 coincides with the physical map location of the functional vasopressin renal V2-type receptor. Recently, the human and rat cDNAs for the vasopressin V2 receptor (AVPR2) have been identified. We show here that the structural AVPR2 gene is localized between DXS52 and G6PD, which is within the genetic map location of DIR. We also tested eight X-linked DIR probands and their families for mutations in one of the most conserved extracellular regions of AVPR2: in three of them, we have identified point mutations resulting in non-conservative amino acid substitutions which cosegregated with DIR in all families. PMID- 1303273 TI - Growing old: the most common mitochondrial disease of all? PMID- 1303274 TI - A major gene for allergy--fact or fancy? PMID- 1303275 TI - More missense in amyloid gene. PMID- 1303276 TI - Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. AB - Prader-Willi syndrome (PWS) is associated with paternal gene deficiencies in human chromosome 15q11-13, suggesting that PWS is caused by a deficiency in one or more maternally imprinted genes. We have now mapped a gene, Snrpn, encoding a brain-enriched small nuclear ribonucleoprotein (snRNP)-associated polypeptide SmN, to mouse chromosome 7 in a region of homology with human chromosome 15q11-13 and demonstrated that Snrpn is a maternally imprinted gene in mouse. These studies, in combination with the accompanying human mapping studies showing that SNRPN maps in the Prader-Willi critical region, identify SNRPN as a candidate gene involved in PWS and suggest that PWS may be caused, in part, by defects in mRNA processing. PMID- 1303277 TI - Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. AB - Prader-Willi syndrome (PWS) is associated with paternally derived chromosomal deletions in region 15q11-13 or with maternal disomy for chromosome 15. Therefore, loss of the expressed paternal alleles of maternally imprinted genes must be responsible for the PWS phenotype. We have mapped the gene encoding the small nuclear RNA associated polypeptide SmN (SNRPN) to human chromosome 15q12 and a processed pseudogene SNRPNP1 to chromosome region 6pter-p21. Furthermore, SNRPN was mapped to the minimal deletion interval that is critical for PWS. The fact that the mouse Snrpn gene is maternally imprinted in brain suggests that loss of the paternally derived SNRPN allele may be involved in the PWS phenotype. PMID- 1303278 TI - A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression. AB - The best examples of imprinting in humans are provided by the Angelman and Prader Willi syndromes (AS and PWS) which are associated with maternal and paternal 15q11-13 deletions, respectively, and also with paternal and maternal disomy 15. The region of the deletions has homology with a central part of mouse chromosome 7, incompletely tested for imprinting effects. Here, we report that maternal duplication for this region causes a murine imprinting effect which may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with AS. Gene expression studies established that Snrpn is not expressed in mice with the maternal duplication and suggest that the closely-linked Gabrb-3 locus is not subject to imprinting. Finally, an additional new imprinting effect is described. PMID- 1303279 TI - Telomere-associated chromosome fragmentation: applications in genome manipulation and analysis. AB - Telomere-associated chromosome fragmentation (TACF) is a new approach for chromosome mapping based on the non-targeted introduction of cloned telomeres into mammalian cells. TACF has been used to generate a panel of somatic cell hybrids with nested terminal deletions of the long arm of the human X chromosome, extending from Xq26 to the centromere. This panel has been characterized using a series of X chromosome loci. Recovery of the end clones by plasmid rescue produces a telomeric marker for each cell line and partial sequencing will allow the generation of sequence tagged sites (STSs). TACF provides a powerful and widely applicable method for genome analysis, a general way of manipulating mammalian chromosomes and a first step towards constructing artificial mammalian chromosomes. PMID- 1303280 TI - Targeted breakage of a human chromosome mediated by cloned human telomeric DNA. AB - Novel approaches to the structural and functional analysis of mammalian chromosomes would be possible if the gross structure of the chromosomes in living cells could be engineered. Controlled modifications can be engineered by conventional targeting techniques based on homologous recombination. Large but uncontrolled modifications can be made by the integration of cloned human telomeric DNA. We describe here the combined use of gene targeting and telomere mediated chromosome breakage to generate a defined truncation of a human chromosome. Telomeric DNA was targeted to the 6-16 gene on the short arm of chromosome 1 in a human cell line. Molecular and cytogenetic analyses showed that, of eight targeted clones that were isolated, one clone had the predicted truncation of chromosome 1. PMID- 1303281 TI - Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A. AB - We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease. PMID- 1303282 TI - Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. AB - We have constructed a 3.1 megabase (Mb) physical map of chromosome 17p11.2-p12, which contains a submicroscopic duplication in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). We find that the CMT1A duplication is a tandem repeat of 1.5 Mb of DNA. A YAC contig encompassing the CMT1A duplication and spanning the endpoints was also developed. Several low copy repeats in 17p11.2-p12 were identified including the large (> 17 kb) CMT1A-REP unit which may be part of a mosaic repeat. CMT1A-REP flanks the 1.5 Mb CMT1A monomer unit on normal chromosome 17 and is present in an additional copy on the CMT1A duplicated chromosome. We propose that the de novo CMT1A duplication arises from unequal crossing over due to misalignment at these CMT1A-REP repeat sequences during meiosis. PMID- 1303283 TI - Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. AB - Expansion of the trinucleotide repeat (CAG)n in the first exon of the androgen receptor gene is associated with a rare motor neuron disorder, X-linked spinal and bulbar muscular atrophy. We have found that expanded (CAG)n alleles undergo alteration in length when transmitted from parent to offspring. Of 45 meioses examined, 12 (27%) demonstrated a change in CAG repeat number. Both expansions and contractions were observed, although their magnitude was small. There was a greater rate of instability in male meiosis than in female meiosis. We also found evidence for a correlation between disease severity and CAG repeat length, but other factors seem to contribute to the phenotypic variability in this disorder. PMID- 1303284 TI - Structure of the X-linked Kallmann syndrome gene and its homologous pseudogene on the Y chromosome. AB - The gene for the X-linked Kallmann syndrome (KAL), a developmental disorder characterized by hypogonadotropic hypogonadism and anosmia, maps to Xp22.3 and has a homologous locus, KALP, on Yq11. We show here that KAL consists of 14 exons spanning 120-200 kilobases that correlate with the distribution of domains in the predicted protein including four fibronectin type III repeats. The KALP locus reveals several large deletions and a number of small insertions, deletions and base substitutions which indicate it is a non-processed pseudogene. The sequence divergence between KAL and KALP in humans, and the chromosomal location of KAL homologous sequences in other primates, suggest that KALP and the steroid sulphatase pseudogene on Yq11 were involved in the same rearrangement event on the Y chromosome during primate evolution. PMID- 1303285 TI - Kallmann syndrome gene on the X and Y chromosomes: implications for evolutionary divergence of human sex chromosomes. AB - The recently identified gene for X-linked Kallmann syndrome (hypogonadotropic hypogonadism and anosmia) has a closely related homologue on the Y chromosome. The X and Y copies of this gene are located in a large region of X/Y homology, on Xp22.3 and Yq11.2, respectively. Comparison of the structure of the X-linked Kallmann syndrome gene and its Y homologue shed light on the evolutionary history of this region of the human sex chromosomes. Our data show that the Y homologue is not functional. Comparative analysis of X/Y sequence identity at several loci on Xp22.3 and Yq11.2 suggests that the homology between these two regions is the result of a complex series of events which occurred in the recent evolution of sex chromosomes. PMID- 1303286 TI - Linkage of Tunisian autosomal recessive Duchenne-like muscular dystrophy to the pericentromeric region of chromosome 13q. AB - Autosomal recessive Duchenne-like muscular dystrophy (DLMD) is a severe dystrophic myopathy. The incidence is unknown because of its clinical similarity to Duchenne muscular dystrophy (DMD). Three highly inbred DLMD families from Tunisia were analysed for chromosomal linkage using 135 polymorphic microsatellite markers. A significant lod score of z = 9.15 at theta = 0.03 was found with the 13q12 locus D13S115. Two additional 13q12 markers, D13S143 and D13S120, also gave significant lod scores. Therefore, the primary DLMD defect gene lies in the pericentrometric region of chromosome 13q. PMID- 1303287 TI - Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain. AB - The levels of a specific mitochondrial DNA deletion (mtDNA4977) measured in 12 brain regions of 6 normal adults 39 to 82 years old exhibited striking variation among anatomical locations. Comparisons of the same region among individuals showed an increase of mtDNA4977 with age. The three regions with the highest levels, caudate, putamen and substantia nigra, are characterized by a high dopamine metabolism. The breakdown of dopamine by mitochondrial MAO produces H2O2 which can lead to oxygen radical formation. We suggest that mtDNA4977 may be the "tip of the iceberg" of the spectrum of somatic mutations produced by oxidative damage. PMID- 1303288 TI - Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. AB - We have examined the role of somatic mitochondrial DNA (mtDNA) mutations in human ageing by quantitating the accumulation of the common 4977 nucleotide pair (np) deletion (mtDNA4977) in the cortex, putamen and cerebellum. A significant increase in the mtDNA4977 deletion was seen in elderly individuals. In the cortex, the deleted to total mtDNA ratio ranged from 0.00023 to 0.012 in 67-77 year old brains and up to 0.034 in subjects over 80. In the putamen, the deletion level ranged from 0.0016 to 0.010 in 67 to 77 years old up to 0.12 in individuals over the age of 80. The cerebellum remained relatively devoid of mtDNA deletions. Similar changes were observed with a different 7436 np deletion. These changes suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing. PMID- 1303289 TI - Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14. AB - Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected. PMID- 1303290 TI - Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24.3. AB - Genetic linkage studies with chromosome 21 DNA markers and mutation analysis of the beta-amyloid protein precursor gene located in 21q21.3 have indicated that early-onset Alzheimer's disease (EOAD) is a heterogeneous disorder for which at least one other chromosomal locus exists. We examined two extended histopathologically confirmed EOAD pedigrees, AD/A and AD/B, with highly informative short tandem repeat (STR) polymorphisms and found complete linkage of the disease to a (CA)n dinucleotide repeat polymorphism at locus D14S43 in 14q24.3 (Zmax = 13.25 at theta = 0.0). Using additional chromosome 14 STR polymorphisms we were able to delineate the region containing the EOAD gene to an area of, at most, 8.9 centiMorgans between D14S42 and D14S53, flanking D14S43 on both sides. PMID- 1303291 TI - A locus for familial early-onset Alzheimer's disease on the long arm of chromosome 14, proximal to the alpha 1-antichymotrypsin gene. AB - Although mutations in the beta-amyloid precursor protein gene (APP) on chromosome 21 cause some cases of early-onset Alzheimer's disease (AD), most cases evidently do not have mutations in APP. We analysed ten early-onset families for linkage to APP and markers elsewhere in the genome. One family (F172) was consistent with linkage to chromosome 21 and was subsequently found to have an APP Val to Ile mutation. Of the others, all but one were consistent with linkage to markers in the middle long arm of chromosome 14. However, no family showed independent evidence of linkage with two point analysis and only one showed independent evidence of linkage on multipoint analysis. Therefore, we cannot rule out heterogeneity at these loci although tests for heterogeneity were not significant. PMID- 1303292 TI - Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. PMID- 1303293 TI - [Two thousand years of historical study on the words atheroma, atheromatosis, atherosclerosis, arteriosclerosis]. AB - Renowned authors, when studying arterial diseases, use indifferently the words atheroma, atheromatosis, atherosclerosis or arteriosclerosis. The historical record of these words permits the justification of a selective choice. The word atheroma was created by Celsius, two thousand years ago; he have it the meaning of fatty tumor, which was kept till the middle of the nineteenth century. The word atheromatosis appeared on 1815, since J. Hodgson defined so the fatty arterial degeneration. Marchand, from Leipzig, proposed on 1904 the word atherosclerosis which has always been with us. The term arteriosclerosis was well defined on 1833 by Lobstein, from Strasbourg. The authors propose to reserve the word atherosclerosis to the arterial disease described by the WHO, to keep the words atheroma and atheromatosis to anatomical lesions well-defined. Arteriosclerosis is a disease which invades an extensive arterial network, with a particular anatomical image. PMID- 1303294 TI - [Antioxidant and/or free radical scavenger vitamins in tropical medicine]. AB - Antioxidant and/or free radical scavenger vitamins (A, E) as beta carotene are unequally distributed among intertropical peoples from Africa. In Ivory coast for example the values observed are clearly enhanced in the regions where Palm oil is usually eaten than in savanna regions. Primary liver cancer (PLC) is more frequently observed in savanna regions. Furthermore it has been recently suggested that retinoic acid which is derived from vitamin A and beta carotene could interact with the genes which are involved in the primary liver carcinogenesis. In PLC patients as in subjects suffering from sickle cell anaemia, malaria, kwashiorkor or marasmus, and AIDS, the plasma levels of vitamin A, Vitamin E and beta carotene are decreased. Though disturbances in the digestion of fats that may be observed in some pathologies (mainly in Kwashiorkor) affect the discussion of the results, haemolysis and/or acute phase reaction with increased respiratory burst are always observed. That explain, at least in part, the lowering of lipophilic-antioxidant-vitamin plasma levels. As a consequence crude palm oil addition or vitamin A and E therapy would enhance the natural defences against the deleterious effects of the oxidative stress induced by these affections. It is worth checking about. PMID- 1303295 TI - [Speech by Mr. Jack Lang, state minister in charge of national education and culture]. PMID- 1303296 TI - Jean-Francois Coste. PMID- 1303297 TI - [The first peopling of Europe: the extraordinary history of Neanderthal Man]. PMID- 1303298 TI - [Organization of psychiatric emergencies in the general hospital]. AB - The authors try to define the notion of psychiatric emergency "pathology covering a whole line of situations characterized by their particularly acute and dramatic behaviors, their constant dealing with human relations, the high frequency of acting out and their usually rapid resolutions" (translated from Vedrinne). They make a brief overview of french psychiatric emergencies departments organization in France either in psychiatric hospitals or in general hospitals. They report the Nancy psychiatric emergencies room's experience, which was born in 1987 and is based on an agreement between the psychiatric "secteurs" and the general hospital. This agreement provides psychiatrists and psychiatric nurses 24h/24, working in a psychiatric room within the medical emergencies department. This experience agrees with the recent french law about psychiatric emergencies. PMID- 1303299 TI - [Drug addiction in Lebanon]. AB - This paper studies the expansion of drug addiction in Lebanon during the years of civil war (1973-1990). A social and historical review of the problem of drugs in Lebanon is presented as an introduction. The profile of the lebanese drug addict is studied in its various components: 1) The average age at hospitalization is around 30 years; the first intake of drugs between 13 and 35 years (mean 20). 2) The sex ratio is 8:2 male to female. The war has especially affected men in their encounter with drugs. 3) Heroin is the most widely used product (80.5%), often in combination with other drugs like hashish or cocaine. Only 17% use it intravenously, the rest by inhalation. 4) There is a certain "democratization" of the phenomenon of drug addiction (23% from the lower socioeconomic class). 5) A preponderance of drug addicts in the big cities like Beirut and Tripoli. 6) Only 20% have an underlying psychopathology responsible for the intake of drugs (psychosis, neurosis). The war has been found conducive to the eclosion of drug addiction by increasing the prevalence of the products, the psychological fragility of the lebanese people, the economic crisis and the more permissive sociocultural context. PMID- 1303300 TI - [Some considerations on long-acting vascular drugs]. PMID- 1303301 TI - [Spectrum analysis of heart rate variability in obstructive hypertrophic myocardiopathy. Evidence of altered autonomic function]. AB - Altered sympathetic activity may play an important role in the pathogenesis of hypertrophic obstructive cardiomyopathy (HOCM). Spectral analysis of heart rate variability was employed to assess the sympatho-vagal function and balance in 18 patients with HOCM (11 males, 7 females, mean age 42 years, range 19-59) and in 15 healthy control subjects (9 males, 6 females, mean age 44 years, range 18-65). Electrocardiographic recordings obtained both at rest and during 60 degrees passive tilt, were digitized and analyzed by fast Fourier transform in order to obtain the power spectrum of heart rate variability. The low-frequency band (LF: 0.05-0.17 Hz) and the high-frequency band (HF: 0.18-0.34) of power spectrum were considered as indexes of sympathetic and vagal activities respectively. A semiquantitative two-dimensional echocardiographic score (SES) was used to assess the entity of myocardial hypertrophy whereas the entity of the intraventricular gradient was determined by continuous wave Doppler. Low-frequency band at rest was slightly but significantly reduced in HOCM group with respect to controls (35.2 +/- 2.0 vs 45.0 +/- 2.5 nu, respectively; p < 0.01), whereas the HF band and the LF/HF ratio were not different in the 2 groups. During tilt, control subjects showed a significant reduction of the HF band (-35%, p < 0.001), an increase in the LF band (+36%, p < 0.001) and a sharp increase in the LF/HF ratio (+105%, p < 0.001). On the contrary the baroreflex increase in the LF band and LF/HF ratio during tilt was markedly blunted, or even reverted, in patients with HOCM (-9%, NS and +5%, NS, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303302 TI - [Evaluation of atrial septum aneurysm with transesophageal echocardiography in cardioembolic cerebral ischemia]. AB - The prevalence and characteristics of atrial septal aneurysm were identified by transesophageal echocardiography (TEE) in a multicenter prospective study. One hundred and seventy-seven consecutive patients were evaluated in 2 years and 2 groups were compared: Group 1, 51 patients with documented cerebral ischemia event; Group 2, 126 patients affected by cardiac disease referred for other reasons. Group 1 included patients selected among 352 patients admitted to the Neurological and Geriatric Division of our Hospital in the period of this study. Patients with stroke-related carotid lesions and patients with a negative TC scan were excluded from this study. Atrial septal aneurysm was identified in 15 patients: 8 in Group 1 (16%), and 7 in Group 2 (5%), with a significant statistical difference between the groups (p = 0.02). All patients with atrial septal aneurysm underwent before TEE transthoracic echocardiography, leading to a correct diagnosis in 10 of 15 cases (66%); all patients underwent 24-hours ECG monitoring. A right to left shunt was detected by contrast echocardiography in 9 patients, 6 in Group 1 and 3 in Group 2, (NS). A more pronounced shunt was evident in Group 1. There was no difference between the 2 groups with regard to associated cardiac disease, arrhythmias and type of atrial septal aneurysm. The thickness of the septum was greater in Group 1, with significant statistical difference (p = 0.002). It is concluded that atrial septal aneurysm, diagnosed by TEE, is a potential source of embolic events. PMID- 1303303 TI - [Prevalence of some cardiovascular risk factors in a sample of the aged population]. AB - The distribution of some cardiovascular risk factors in a cohort of elderly population is reported. The study population consisted of 427 males aged 71-91, examined in 1991 and belonging to the Italian rural section of the Seven Countries Study on Cardiovascular Diseases. Systolic blood pressure shows an increasing trend with age, with mean levels greater than 160 mmHg in each quinquennium, while the prevalence of hypertension ranges between 60 and 75%. Other risk factors considered such as serum cholesterol, triglycerides, weight, height and smoking habit show decreasing levels with ageing. This trend is clear also for fasting glucose from the age group 76-80. PMID- 1303304 TI - Comparison of ST segment changes on standard and Holter electrocardiogram during exercise testing. AB - In order to compare the ST segment changes recorded simultaneously on Holter (Del Mar Avionics 445B recorder and DCG VII Scanner) and standard electrocardiogram, 22 patients with chest discomfort and normal resting ECG were evaluated during exercise testing. The conventional ECG was recorded using chest lead V5 and a modified lead II. The Holter recording was done using the bipolar chest lead CM5 and the same modified lead II. Bifurcating electrodes permitted simultaneous recording of electrocardiogram on both systems from the same electrode sites. Seven of the 22 patients had a positive test and 15 had a negative test by both systems. In 7 positive cases the amplitude of ST segment depression was compared. The Holter lead CM5 showed higher amplitude of ST segment depressions in 6 cases compared to the conventional lead V5: 3 cases by 0.5 mm; 2 cases by 1 mm and 1 case by 2.5 mm. In 1 case it was identical. The amplitude of ST segment depression in lead CM5 ranged from 1 to 3.5 mm (mean 2.2 +/- 0.6 mm) and in lead V5 from 1 to 2.5 mm (mean 1.5 +/- 0.6 mm). Thus the amplitude of ST depression was higher in lead CM5 by a mean of 0.7 mm compared to the lead V5. ST segment depression was present only in 6 cases in the modified lead II. ST segment depressions were reproduced faithfully in 3 patients and within the variation of 0.5 mm in other 3 cases by the Holter system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303305 TI - [Coronary disease in women as opposed to men]. PMID- 1303306 TI - Changes in sarcolemmal proteins in subacute myocardial infarction in the dog. AB - Previous studies have shown degradation of cardiac structural proteins and disruption of the sarcolemma as a result of acute myocardial infarction. However, there is no evidence to date on changes in sarcolemmal membrane proteins induced by experimental subacute myocardial infarction. We studied subepicardial layers overlying myocardial infarct 4 days following ligation of the left anterior descending coronary artery in 12 dog hearts. We first demonstrated that this layer provides the anatomic-electrophysiologic substrate for reentrant arrhythmias using activation mapping techniques and histologic correlations. The makeup of membrane proteins was studied using SDS polyacrylamide gel electrophoresis, peptide mapping, and laser densitometry. Sarcolemmal membrane proteins were isolated by ultracentrifugation through a sucrose gradient. We found that a sarcolemmal polypeptide (MW 126,000; n = 12) in the normal tissues has a different mobility than the corresponding protein (MW 124,000; n = 12) of the ischemic tissues although their peptide analysis appeared similar, suggesting that the protein undergoes a post-translational modification. In addition, two proteins (MW 75,000; n = 12 and MW 88,000; n = 12) were present in greater amount in the ischemic than in the control tissues suggesting either acceleration in protein synthesis or slow down of degradation turnover. These results demonstrate that specific changes occur in membrane proteins subjected to ischemic insults which might be responsible for membrane alterations following ischemia and may contribute to the abnormal electrophysiologic properties and arrhythmia seen in vivo at this stage. PMID- 1303307 TI - Ascorbic acid modulates collagen type I gene expression by cells from an eye tissue--trabecular meshwork. AB - The trabecular meshwork, a specialized tissue in the anterior chamber of the eye, plays a major role in the regulation of aqueous humor outflow. We studied the effects of ascorbic acid, a significant component in the aqueous humor, on gene expression of type I collagen in cultures of bovine trabecular meshwork cells. These cells were plated for 6 days, exposed to ascorbic acid in concentrations of 100, 250 and 500 micrograms/ml for 3 days and labeled with (3H)proline for the last 24 hrs. Cultures that did not receive ascorbic acid served as controls. Bacterial collagenase assays showed enhanced incorporation of (3H)proline into collagenous proteins in cultures treated with 100 and 250 micrograms/ml of ascorbic acid. Gel electrophoresis and fluorography revealed that ascorbic acid caused a 2.6- to 4.9-fold increase in production of alpha 1 (I) and alpha 2(I) collagen chains by trabecular meshwork cells. Such an increase was found, using a cDNA probe specific for pro alpha 1(I) chains, to be accompanied by an increase in steady-state mRNA levels. Similar findings were also yielded from in situ hybridization experiments. These results, coupled with previously demonstrated ascorbate-induced effects on glycosaminoglycan, fibronectin and laminin synthesis, suggest that ascorbic acid is a key mediator of the extracellular matrix production by trabecular meshwork cells. Fluctuations in its concentration may lead to alterations in the makeup and assembly of matrices underlying the cells. PMID- 1303308 TI - EGF receptor activity and mitogenic response of Balb/3T3 cells expressing Ras and Myc oncogenes. EGF receptor activity in oncogene transformed cells. AB - EGF receptors are found on the surface of most cells, usually with high and low binding affinities. To investigate functional relationships between EGF (EGF-like growth factors) and oncogenes we have characterized the expression of the epidermal growth factor receptor (EGFr) in H-Ras, v-Myc, and H-Ras-v-Myc transformed Balb/3T3 cells. H-Ras cells show a marked decrease in the number of EGFr molecules per cell compared to parental cells. v-Myc and H-Ras-v-Myc transformed cells express an intermediate level of receptors. The majority of the EGF receptors on the parental and oncogene transformed cells bind EGF with low affinity and this low affinity receptor is down-regulated by oncogene transformation. v-Myc expression, in the H-Ras-v-Myc transformed cells, abrogates the receptor down-regulation seen with H-Ras transformation. The mechanism of abrogation is not a result of a change in the p21-Ras concentration in the H-Ras v-Myc transformed cells. In addition, the mitogenic response to EGF was examined. H-Ras and H-Ras-v-Myc transformed cells do not respond to EGF mitogenically. In contrast, EGF stimulates DNA synthesis in parental cells and v-Myc transfected cells; this result suggests that growth promoting signals from the EGF receptor may not be required in H-Ras transformed cells. PMID- 1303309 TI - [Epidemiologic characteristics of liver cancer in the youth in Qidong high-risk area]. AB - This paper reports the epidemiologic characteristics of liver cancer in the youth aged 0-34 years during the period of 1972-1989 in Qidong high-risk area. The mortality for liver cancer in the youth was 11.59 per 100,000 (age-adjusted rate, 9.55 per 100,000), which accounted for 15.45% of that in the total population, and 61.55% of all cancers in the youth. Significant sex-difference was also seen in the youth: 18.60 per 100,000 (age-adjusted rate, 15.79 per 100,000) in males and 4.50 per 100,000 (age-adjusted rate, 3.60 per 100,000) in females. The male to-female ratio was 4.13: 1, showing that liver cancer occurred more frequently in early-adult life in males than females. There was a rising trend in crude mortality of liver cancer in the youth over this period, but after adjusting for age, the rate showed a slight decrease. It might be expected that, owing to expanded immunization with hepatitis B vaccine in Qidong newborns since 1983, the further decrease of liver cancer mortality in Qidong should be seen in the youth. PMID- 1303310 TI - [An epidemiological analysis on the geographic factors of esophageal cancer]. AB - The author collects the data of esophageal cancer mortality (1971-1973) of 78 counties in Hubei Province and the data of topography, climate, soil, rock formation and geochemical elements, including 40 suspected factors. The method of linear correlation and multiple stepwise regression are used for the comprehensive analysis of relation between the geographical factors and esophageal cancer. The result is that four factors metamorphic rock, zinc, copper, chromium are suspected factors. It suggests that the four factors will need future study. PMID- 1303311 TI - [An investigation on hepatitis B infection in the women with sexual abuse]. AB - A serological investigation on hepatitis B virus (HBV) infection in women with sexual abuse was made in mainland China. In such women, the HBV infection rate and the positivity rate of HBsAg were higher than those in normal healthy conditions. It was suggested that sexual abuse was a important factor for HBV infection and the women with sexual abuse were one of the most dangerous sources of the HBV infection. The results of investigation also showed that in women with sexual abuse, HBV infection was not related to whether they were suffering from Venereal Diseases (VD) or not; but the existence of VD might probably exacerbate the process of hepatitis B. PMID- 1303312 TI - [The possible role of sperm in family HBV infection]. AB - The paper investigated HBV infectious markers in the sperm and spermatozoa of 31 male patients with hepatitis B, in the serum of their 31 spouses and 35 children respectively. HBV markers were found in 12 sperm samples, HBV-DNA was detected in 6 samples of spermatozoa (3 integrated forms and 3 free forms). The samples were hybridized repeatedly with probes of 82P labeled HBV-DNA 82P labeled lambda DNA and 82P labeled pBR822 to exclude false-positive possibility. 8 out of 12 wives (66.67%), were infected whose husband's sperm reacted positively with HBV 8 out of 14 children were infected (57.14%), whose father's sperm had HBV markers, 6 women out of 19 were infected (31.58%) whose husband's sperm did not react with HBV, 11 of 22 children were infected (50%). The investigation found that the HBV in sperm was higher in the patients with HBeAg positive serum. The wives were easier infected from husbands with HBV positive sperm. The result suggested that sperm must be one of medium of HBV transmission. HBsAg HBeAg anti-HBc HBV-DNA were found in the serum sample of one 4 month infant, with no anti-HBc-IgM. His mother was negative in HBV. The integrated form HBV-DNA was detected in his father's spermatozoa. The transmission between father and son is perhaps mainly by contact each other daily. If HBV has the possibility of vertical transmission is to be studied. PMID- 1303313 TI - [A case-control study on risk factors of cerebral hemorrhage]. AB - A case-control study to investigate the risk factors of cerebral hemorrhage was conducted in 162 hospitalized patients diagnosed by head CT scan in Tianjin, 1988 89. Each patient was matched at the same time by one hospital control and one community control. Multivariable conditional logistic regression analysis showed that history of hypertension or TIA, stroke history of parents and snoring were found to be the risk factors of cerebral hemorrhage, without involvement of smoking. PMID- 1303314 TI - [A study on risk factors of ischemic stroke]. AB - In order to investigate risk factors of ischemic stroke, a matched case-control study with two kinds of controls (community controls and hospital controls) was conducted. The multiple conditional logistic regression analysis showed that hypertension, transient ischemic attacks, alcohol consumption and habitual snoring were independent risk factors of ischemic stroke. Physical activity at leisure time was an important protective factor. No independent relationships were found between cigarette smoking, history of mellitus diabetes or heart diseases, stroke history of father or mother and ischemic stroke. PMID- 1303315 TI - [Primary analysis on hypertension community control in East City]. AB - In order to carry out chronic disease prevention, a hypertension community control program has been conducted in Disease Surveillance Point, East City. Beijing since 1989. The resident committees were randomly divided into two groups. The community control activities were conducted in intervention group, which included home visit, health education. 3190 hypertensive cases were managed in 1991. Current smoking rate was decreased 8.37%, quit and reduce smoking increased 5.81%, drinking decreased 8.77%, reduced salt intake 5.45%, DBP < 95 mmHg increased 27.81%, when compared with base line survey in 1989. These indicators were significant between intervention and control groups. It means hypertension community control program is successful. PMID- 1303316 TI - [The matched case-control study of the risk factors associated with edema proteinuria hypertension syndrome (EPHS)]. AB - This paper conducted a matched case-control study to determine the possible risk factors associated with EPHS. 208 cases and 208 matched controls were selected from two affiliated hospitals of Tianjin Medical College between 1 Dec. 1986 and 30 Oct. 1987. The conditional logistic regression analysis showed that basic diastolic blood pressure, the history of hypertension TH Time Hurry) +CH (Competition and Hostility) scores and quetelet index were the major risk factors. The odds ratio (OR) and 95% confidence of OR for these factors were 1.08 (1.04-1.12), 3.58 (1.88-6.83), 1.05 (1.03-1.09), 1.17 (1.05-1.31), respectively. Compared with Type B behavior, OR for Type A behavior is 3.06 (2.24-4.19). OR for women with history of hypertension of her father is 2.5 (1.49-4.20). The lower the average family income, education level, the higher the risk of EPHS. Basic systolic blood Pressure and body weight were positively related to EPHS. Did not find relationship between fetal sex, maternal age, parity, age of menarche, rest period during pregnancy and EPHS. PMID- 1303317 TI - [Hypertension risk factors and epidemiological study in the countryside]. AB - This paper reported the results of a matched (1:2) case-control study of 218 pairs on Essential Hypertension in the countryside of Sichuan Province in 1989. Conditional Logistic regression technique was used in data analysis. It was showed that Essential Hypertension and borderline Hypertension was associated with heart rate, family history of Hypertension, environmental noise, QI factors, while borderline Hypertension was associated with smoking, too. The association of Essential Hypertension with smoking and drinking has not been found. Heart rate is the test parameter necessary for blood pressure research. PMID- 1303318 TI - [An outbreak of rubella with a cinema as source]. AB - An outbreak of rubella occurred in four primary schools at jiu-bao town Yuhang county from twentieth Dec. 1989 to twelfth Feb. 1990. Attack rate was 37.46%. The patients had typical clinical features, and its prognosis was good. Average latent period was 17.8 days. The outbreak was suggested to related to a cinema, the first generation of 196 cases had the history of going to the movies. There was no case among those who had not gone to the same cinema at the same period. The highest attack rate was 56.97% in a primary school. The highest attack rate of age group was at 10-15 year group (48.40%), the rubella IgM positive rate at 2 5 days and 6-20 days were 52.63% and 76.66% respectively. 30 days later, no positive result was found. PMID- 1303319 TI - [Evaluation of long-term efficacy on plasma-derived hepatitis B vaccine]. AB - From April 1986 to May 1990, 265 pupils aged 5 to 9 years in Xian suburbs were studied to evaluate long-term efficacy of plasma-derived hepatitis B vaccine made in China. Anti-HBs titers in vaccine group reached the highest at twelfth month after the first injection and decreased afterwards. The positive rate of anti-HBs decreased slow, but geometric mean titers of anti-HBs fell sharply. Compared with placebo group, the differences were all significant. The peak anti-HBs titers and the response time positively correlated with the persistence of anti-HBs. 4 years observation showed that protection rate of hepatitis B vaccine against HBV infection was 80%. Protection rate was 100% if HBsAg was only considered. PMID- 1303320 TI - [An investigation of sequelae of paralytic poliomyelitis in some districts of inner Mongolia autonomous region]. AB - Three hundreds and twelve sequelae of paralytic poliomyelitis were diagnosed among 163,013 lame children under 12 years of age. The prevalence of paralytic poliomyelitis was 1.91%. The result showed that although the morbidity of poliomyelitis has greatly decreased since the programme on immunization against polio were introduced, there were still a number of unreported cases. Of the cases diagnosed, ninety-three per cent were those who were unvaccinated and were mostly infected in the first four years of life. PMID- 1303321 TI - [Epidemiological study on mycoplasmas colonization and infection in the female genital tract]. AB - 1309 cervical or vaginal specimens from females in various physiological periods and women with multiple sexual partners were examined for Ureaplasma urealyticum and Mycoplasma hominis from Feb. to May, 1990. Significantly, low carriage rates of U.urealyticum were found in the neonatal (28.57%), puerperium (26.51%) and postmenopause (30.00%) groups, whereas, pregnant women (more than 36 weeks) showed the highest incidence (73.20%). The recovery rate of U. urealyticum in girls with no history of sexual contact was significantly lower (38.30%) than that in married nonpregnant women (48.98%) and women with multiple sexual partners (71.74%). The incidence rate of the genital mycoplasmas was significantly affected by the type of contraception, the number of sexual partners, socioeconomic states, degree of cultural traditional, as well as hormonal status. Possible modes of transmission of genital mycoplasmas were also discussed. PMID- 1303322 TI - [Influenza surveillance]. AB - From 1982 to June 1990, seven influenza A (H3N2) epidemics and four influenza A (H1N1) epidemics occurred in Shanghai, and several new variants of influenza virus were isolated. During that period, influenza A (H3N2) and influenza A (H1N1) appeared alternatively while each lasted for one to two years. The epidemic peak of influenza usually was seen from July to August and late winter to early spring. The subtype which appears in July and August usually starting in late winter and early spring in Shanghai causes epidemics in the northern regions of China and some other countries in the northern hemisphere. If minor epidemics occur only in July and August, further antigenic changes may cause moderate epidemics in late winter and next early spring. Information supplied for prediction of influenza epidemics and timely preparation of new vaccines may lead to better control of influenza. PMID- 1303323 TI - Freeze-fracture studies of salivary glands. AB - Freeze-fracture electron microscopy was employed to study the general morphology, membrane fusion during exocytosis, intercellular junctions in adult and developing salivary glands, and morphological changes of intercellular junctions in secretory stimulation and neoplastic disorders. Intramembranous particles distributed on plasma membranes and organelle-membranes were determined on the basis of particle density per unit. Relationship between distribution and density of particles and functions of membranes and organelles was discussed. Fused membranes took the form of smooth areas of intramembranous particles free on the PF face in the submandibular acinar cells induced by isoproterenol stimulation. The sequence of membrane fusion during secretion was discussed from these freeze fracture observations. Tight junctions which limited solute diffusion between adjacent cells formed continuous belts around the juxtaluminal region of plasma membrane. Their permeability function was regulated by the number and the geometrical pattern of the tight-junctional strands. The junction appeared late during gestational life, and its development and morphology correlated with the establishment of electrochemical tightness. Similarity in the location and morphology between developmental and neoplastic conditions might indicate reflect the function and degree of cytodifferentiation in salivary gland. Gap junctions were detected as clusters of particles, representing voltage-regulated intercellular channels connecting adjacent cells. The junctions were developmentally regulated, and their size and frequency correlated with the functional activity and with cytodifferentiation in neoplastic disorders. Desmosomes, which appeared as round or elongated clusters of particles, provided the mechanical stability necessary to maintain the organization of acini and ducts. PMID- 1303324 TI - Analysis of cell surface antigens of Campylobacter rectus. AB - Campylobacter rectus is one of the predominant bacteria in the lesions of human periodontitis. The surface antigens of the bacterium contain several components which may play significant roles in colonization and pathogenesis. A high molecular-weight protein was selectively isolated from the cell surface of C. rectus by acid extraction and purified by DEAE Sepharose. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the extracted protein was 150 kDa. The protein was not found in Campylobacter curvus ATCC 35224 or Wolinella succinogenes ATCC 29543. Lipopolysaccharide (LPS) was extracted from various C. rectus strains by the hot phenol-water method. SDS-PAGE patterns revealed that C. rectus LPS was the smooth type in nature. Monoclonal antibodies against C. rectus were generated by the fusion of SP2/0 myeloma cells with splenocytes from BALB/c mice immunized with whole cells of C. rectus ATCC 33238 strain. An Immunoglobulin G1 monoclonal antibody reacted with the high-molecular weight proteins from 4 of 9 C. rectus strains, indicating that the 150 kDa protein exhibits antigenic heterogeneity. Immunoelectron microscopic study revealed that the monoclonal antibody recognized the S-layer of C. rectus cells. An IgM monoclonal antibody reacted with LPSs from C. rectus strains at molecular weights between approximately 20.0 kDa and 24.0 kDa. The monoclonal antibody did not react with any other LPSs from C. curvus ATCC 35224 or W. succinogenes ATCC 29543. The reactivities of this monoclonal antibody indicate that it recognizes an O-specific side chain epitope of C. rectus LPS. Sera from patients with adult periodontitis showed strong reactivity with the 150 kDa protein antigen and LPS from C. rectus strains. As determined by immunoblotting analysis, sera from periodontally healthy individuals, however, showed little or no reactivity. The levels of serum IgG antibodies of patients with periodontitis to the protein antigen and LPS were statistically significantly higher than those of periodontally healthy individuals, as assessed by an enzyme-linked immunosorbent assay. PMID- 1303325 TI - Comparison of spatial resolution between tomographic images and ghosts in rotational panoramic radiography: the effect of the first slit width. AB - Rotational panoramic radiography projects the object placed within the focal trough as tomographic images with minimal distortion. However, even if an object is within the focal trough, the sharpness of the image is affected by the position of the object, the difference in the relative speed of the X-ray source against the film and the difference in the direction of rotation. In this study, spatial resolutions of ghosts and tomographic images were compared. Ghosts, as well as tomographic images, were obtained from the object placed in the focal trough. The effects of the width of the first slit, a major parameter affecting image quality, were the primary concern in this study. With regard to ghosts, the influence of the position of object, in terms of central, buccal and lingual regions the focal trough, was also analyzed. The target of analysis was the mandibular ramus region. An Orthopantomograph OP5, a conventional panoramic apparatus, was used. An X-ray test chart, X-ray beams, and H-D curve were prepared for calculation of the Modulation Transfer Function (MTF), and the slit method using the Fourier transforms was applied. When the width of the first slit was changed displacement of MTF curves was most remarkable for the superimposed tomographic image which was scanned 10 mm posterior to the X-axis connecting the right and left lateral rotation centers. For reduction of the spatial resolution of ghosts, it was found effective to use a wider slit and place the object at a position lingual to the central plane. PMID- 1303326 TI - A study of the internal structure of the Japanese mandible. AB - The thickness of the substantia compacta and the volume and width of the trabecular bone of the substantia spongiosa were investigated by soft X-ray photographs made of thin sections of many kinds of dentulous and edentulous mandibles. The results were: 1) The thickness of substantia compacta is especially thick on the lingual side in the incisor region and thickest in the molar region in all materials. At the base of mandible, the thickness is essentially the same in all regions, but, the thickness of dentulous materials is greater than of edentulous ones. 2) On the upper part, the volume of trabecular bone is less in the premolar region in both edentulous and dentulous material than in other regions, however, there is relative more in edentulous than in dentulous. In the central part, there is almost the same amount of trabecular bone in the dentulous and edentulous material. 3) The width of the trabecular bone in the substantia spongiosa is greater in the incisor region than in other regions in all materials. In the upper and central part, it is smaller in the premolar region in both edentulous and dentulous material but, it increases in the molar region in the edentulous materials. PMID- 1303327 TI - [Alteration in resistance of Plasmodium falciparum to chloroquine after cessation of chloroquine medication for twelve years]. AB - In view of the fact the resistance of Plasmodium falciparum to chloroquine occurred extensively in Hainan, a decision was made in 1979 that the use of chloroquine should be quit in the whole province. A longitudinal survey on chloroquine-sensitivity of P. falciparum was carried out during 1981-1991 to observe the variation in resistance of the parasite after the cessation of the chloroquine medication for every 2-3 years. A tendency of progressive decline of resistance was revealed. By using in vitro test, the rate of chloroquine resistant P. falciparum dropped from 97.9% in 1981 to 60.9% in 1991 (P < 0.001). The mean dosage of chloroquine for complete inhibition of schizont formation declined from 10.46 pmol/microliters in 1981 to 3.02 pmol/microliters in 1991 (P < 0.001). The percentage of population requiring larger dosage (6.4 pmol/microliters to completely inhibit schizont formation declined from 83.3% in 1981 to 17.4% in 1991 (P < 0.001); whereas those requiring small dosage (1.6 pmol/microliters), increased from 4.2% in 1981 to 60.8% in 1991 (P < 0.001). In in vivo test, the rate of chloroquine-resistant P. falciparum decreased from 84.2% in 1981 to 40% in 1991 (P < 0.001). The proportion of RII plus RIII cases of the total resistant cases dropped from 59.4% in 1981 to 37.5% in 1991 (0.02 > P > 0.01). PMID- 1303328 TI - [Studies on the strain differences of Schistosoma japonicum in the mainland of China. XI. Enzyme linked immunoelectrotransfer blot analysis]. AB - Antigens prepared from S. japonicum adult worms of different isolates i. e. Anhui, Hubei, Guangxi, Yunnan and Sichuan by origin were analyzed by enzyme linked immunoelectrotransfer blot (EITB) probed with rabbit anti-snail antibody (Figs 1,2). Anti-sera against Oncomelania h. hupensis from Anhui, Hubei, Yunnan and Sichuan localities were prepared separately and used in the tests. The EITB patterns were similar in S. j. isolates of Anhui and Hubei, and it was also the case among S. j. isolates of Yunnan and Sichuan except Yunnan female worms with a marked band of 84 kDa but it was almost invisible in EITB pattern of Sichuan female worms. Like Yunnan isolate, female worms of Guangxi isolate also showed marked 84 kDa bands. The EITB pattern of male worms from Guangxi isolate showed 2 main bands of mw > 130 kDa against anti-Anhui snail anti-serum, which corresponded with the male worms of Anhui isolate whereas the color of the bands was darker and denser in the former isolates, and these bands can not be seen in the male worms from isolates of Yunnan and Sichuan. Based on the above mentioned results in connection with the information about the susceptibility between different isolates of schistosomes and their snail hosts which we have reported before, some preliminary analysis and discussion were made. PMID- 1303329 TI - [Studies on the establishment of malarial animal model of short-term relapse. II. The phenomenon of sustained special ring form parasitemia in Plasmodium cynomolgi infection]. AB - Our previous report that the EE merozites of Plasmodium cynomolgi from Vietnam continuously released from the liver to the blood circulation was further demonstrated in this report. Monkeys were given pyronaridine 24 mg/kg.d x 6 after being inoculated intravenously with 32 x 10(5) sporzoites of P. cynomolgi. Thick blood film examination was conducted two times daily till the day when trophozoites were detected. Under the residual action of blood schizontocied, a special ring form parasitemia at low patasite-density was detected for more than 30 days. As the ring forms of P. cynomolgi were demonstrated to be susceptible to pyronaridine in our previous experiments, it might be inferred that these ring forms derived from EE merozites released not for once but continuously for 30 days or longer. PMID- 1303330 TI - [Field observation on the population fluctuation of Oncomelania snail at low density in plain region]. AB - Field observation on the population fluctuation of Oncomelana snail at low density was carried out in the ditches and rivers in Wuxi, Ludong and Lugao counties (or city) from 1987 to 1990. The results showed that the environment of the observed places is an important factor in the population fluctuation of the snails at low density. When the environment is appropriate, even one pair of the snails may multiply to a large population. Results of successive observation for 3 years on 1, 5 and 10 pairs of snails within nylon cages in ditches showed that the density of the snails increased by 171.5, 69.5 and 28.4 folds respectively and the population of the snails increased by 354, 135 and 75 folds respectively. The population in 2 of the observed ditches with one pair of snails each even multiply by 543 and 426.5 folds. While in natural field condition, the population fluctuation of residual snails varied in different places. In one ditch it multiplied by 34.7 folds, but in another river the population almost unchanged. No natural elimination of snails could be found in all observed places. It was suggested that the snail surveillance should be conducted persistently and any snail once be found, it should be timely eradicated. PMID- 1303331 TI - [Study on the effect of bromoacetamide upon the development of snail eggs]. AB - This paper deals with the influence of bromoacetamide on the development of snail eggs, its effect on inducing diapause of snail eggs at different developmental stages (blastula, gastrula, trochophore and veliger) both at different concentrations of bromoacetamide at the same time and at same concentration at different times. Besides, the oviposition of the snails and the eggs within snails have also been studied. The results are as follows: 1. When the snail eggs were immersed in bromoacetamide at concentrations of 0.034ppm-0.067ppm, deformation of snail eggs appeared from unicellular to gastrula stages, but it was not observed after the trochophore-veliger stages. When the eggs at different stages were separately immersed in bromoacetamide, they were all found deformed. The molluscicidal concentration for inducing deformation of eggs was higher at the trochophore-veliger and metamophotic stages than that at the blastula and gastrula stages (Figs. 1-5). 2. After immersed in bromoacetamide solution, the development of the snail eggs were obviously retarded. The effects varied with different concentrations. Within the same exposure time, the higher the bromoacetamide concentration, the higher the diapause rate. 3. The longer the immersion time, the lower concentration was needed to delay the development and the lower hatching rate was for the eggs at the same or different stages. 4. After treatment with bromoacetamide, the average number of eggs laid by a female snail was reduced. 5. By using 3H-labeled bromoacetamide, it was found that the radioactivity of 3H-labeled bromoacetamide per hundred snail eggs was raised along with the increasing of the molluscicide concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303332 TI - [Leishmaniasis in Karamay. XI. The development of cutaneous leishmaniasis in monkey and man experimentally infected with Leishmania from Karamay big gerbil]. AB - A monkey (Macaca rhesus) was inoculated subcutaneously with 2 Leishmania isolates (MRHC/CN/88/KXG-2 and MRHO/CN/90/KXG-56) from Karamay big gerbils (Rhombomys opimus) into the forehead and cheek, 36 days later ulceration with a diameter of 0.2cm occurred at 2 sites. The lesions persisted for 60 and 95 days respectively and then healed spontaneously. However, Leishmania could be detected from the dermal tissue for more than one year. When MRHO/CN/88/KXG-2 isolate was inoculated into the forearm or ear of the monkey, no ulceration but swelling was revealed at the sites of inoculation. Leishmania was found to be latent in the subcutaneous tissue of the forearm for more than 103 days. The monkey was dissected one year after inoculation, no evidence of visceral involvement was noted. Another isolate (MRHO/CN/87/KXG-12) was inoculated subcutaneously into the forearm of 2 healthy volunteers. One of them developed cutaneous leishmaniasis. An ulcer with a diameter of 0.4cm and a nodule as large as 0.9 x 1.5cm around the ulcer occurred at the inoculation site 128 days later. Leishmania parasites were found harboring in macrophages of the dermis and in the epithelial cells of hair follicles. The results indicate that Leishmania parasite of the Karamay big gerbils is pathogenic to monkey and man, in addition to the fact that human cutaneous leishmaniasis and gerbil's Leishmania co-exist in Karamay, it seems that big gerbil is a potential reservoir of human cutaneous leishmaniasis in this area. PMID- 1303333 TI - [DNA probe for identification of sibling species of Anopheles sinensis and Anopheles anthropophagus]. AB - Genomic DNA libraries of Anopheles sinensis and Anopheles anthropophagus were constructed. The positive clones suitable for discrimination sibling species of An. sinensis and An. anthropophagus were screened and a clone from An. sinensis DNA library was selected and the insert DNA was used as a DNA probe to test dot blot of genomic DNA from An. sinensis and An. anthropophagus. The results showed that the DNA probe hybridized with all stages of An. sinensis DNA, but had very weak hybridization signal with An. anthropophagus DNA. The probe was very sensitive and could detect as little as 7.5ng An. sinensis which represents approximately one-150th part of the total DNA from single mosquito. The results demonstrated that the DNA probe reported here could be used to distinguish species of An.sinensis from An. anthropophagus. PMID- 1303334 TI - [Serological epidemiologic surveillance on filariasis by ELISA]. AB - In 1984-1990 longitudinal or sectional serological surveillance on filariasis by ELISA with Brugia malayi adult antigen was carried out in 6 villages, Yuhang County, Zhejiang Province, where malayan filariasis had been under control. During that period the microfilaraemia rate of inhabitants had been declining continuously till nil, the positive rate and mean optical density (OD) value in ELISA for positive inhabitants concurrently declined year by year, especially for children under age of 10. By the 5th year after control both the positive rate and mean OD value were close to those of healthy persons living in nonendemic areas of filariasis, no positivity was found in children. In the meantime, ELISA was used to detect serum antibodies in members of a family who were infected with bancroftian filariasis and inhabitants living around them in 1990. Positive rate of ELISA was higher in these inhabitants (8.33%) than in healthy persons (2.53%), and positive ones were detected from children under age of 10. The results suggest that the detection of antifilarial antibody by using ELISA is an effective method for the surveillance of filariasis. PMID- 1303335 TI - [In vitro liver microsomal metabolism of antimalarial primaquine]. AB - The profile of the major metabolites of primaquine produced by in vitro liver microsomal metabolism was investigated with silica gel thin-layer and high performance liquid chromatography (HPLC) analysis. The results indicated that the liver microsomal metabolism could simultaneously produce both 5-OH PQ (quinoline ring oxidation product) and CPQ (side-chain oxidative deamination product). However, the quantitative comparative study of microsomal metabolism showed that the production of 5-OH PQ was far much higher than that of CPQ. PMID- 1303336 TI - [Clinical observation on efficacy of ivermectin in the treatment of intestinal nematode infections]. AB - A total of 166 cases were divided into 3 groups: group A comprised 55, group B 54 and group C 57 cases. Group A received ivermectin 0.1 mg/kg orally at a single dose, the cure rates were 100%, 3.8% and 50% for ascaris, hookworm and trichuris, infections respectively: group B received ivermectin 0.2 mg/kg orally at a single dose, the corresponding cure rates were 95.5%, 11.8% and 76.5% respectively; group C received pyrantel pamoate 10 mg/kg orally at a single dose, the corresponding cure rates were 95.5%, 29.6% and 31.6% respectively. Although the cure rates were very low for hookworm infection in both group A and B, however, a number of adult worms of Ancylostoma duodenale and Necator americanus were expelled aster medication; It indicates that ivermectin has some effects on these two species of human hookworm. Side effects were mild and transient in all groups. PMID- 1303337 TI - [Distinguishing Anopheles dirus of Hainan Province by gas chromatography of cuticular hydrocarbons]. AB - In order to identify the members of Anopheles dirus complex of Hainan Province an analysis of relative content of cuticular saturated n-paraffins of Anopheles dirus collected from different localities and in different months in Hainan Province was performed by using gas chromatography. The difference among the cuticular hydrocarbons n-paraffins components was statistically insignificant. The values of stepwise cluster analysis (Q model) were very close for all the collected populations. These data suggested that there might be one species of Anopheles virus complex which was further confirmed by the similarities between blood preference, seasonal variation, and nocturnal activity. PMID- 1303338 TI - [Hybridization experiments using Anopheles minimus from Guangxi and Yunnan]. AB - Hybridization experiments were conducted by forced mating between Anopheles minimus from Guangxi (G) and Yunnan (Y). F1 hybrid females were all fertile with normally developed ovaries. (Y female x G male) F1 males were all sterile, with abnormally enlarged testes. (G female x Y male) F1 males, though fertile, showed somewhat atrophic testes, and when they were back crossed with parental females, the latter produced eggs with very low hatching rate. Ovarian nurse cell polytene chromosomes from F1 hybrid females showed partial asynapsis in X chromosome as well as in autosonles, asynapsis at 38 zone in 3L being the most constant. It was obvious that there was definite, though partial, reproductive isolation between An minimus from Guangxi and that from Yunnan. Whether they are sibling species remains to be further investigated (Figs. 1-8). PMID- 1303339 TI - [Studies on the antimalarial action of gelatin capsule of Artemisia annua]. AB - The pharmacological and clinical effects of gelatin capsule of Artemisia annua (GCAA) were investigated. The results revealed that the LD50 was 162.5 +/- 10.1g (crude drug)/kg and ED50 was 11.9 +/- 2.4g (crude drug) for clearance of parasitemia in mice infected with Plasmodium berghei therapeutic index being 13.6, which was 3.5 times more than that of artemisinin. The cure rate of COEA for Plasmodium berghei and P. vivax infections was 100%, as well as just like that of the extract tablets of Artemisia annua and chloroquine. This formulation was found to be better than chloroquine in fever subsidence and disappearance of malarial symptoms, while the recrudescence rate was still high, the latter could be inhibited by increasing therapeutic course or daily dosing time or by combination with primaquine. PMID- 1303340 TI - [Immunohistochemical localization and histochemical observation of antigens in Pagumogonimus skrjabini]. AB - Using immunohistochemical method, the antigens were shown to be mainly located in the cecum, tegument, esophagus, pharynx, excretory bladder, uterus and oral sucker of Pagumogonimus skrjabini. Histochemical analyses showed that antigens contained enzymes such as acid phosphatase (ACP), alkaline phosphatase (AKP), and acetylcholinesterase (AChE). Other chemical substances, for example, alkaline protein, basic protein, glycogen and acid mucopolysaccharides were also detected in the antigens of P. skrjabini. PMID- 1303341 TI - [Further observation on the ultrastructure of the sporocyst of Schistosoma japonicum]. AB - A further observation was conducted on the ultrastructure of mother sporocyst (Ms) daughter sporocyst in the brood chamber (b-Ds), migrating daughter sporocyst (mi-Ds) and daughter sporocyst in the liver tissue (1-Ds) of Oncomelania hupensis by scanning and transmission electron microscopy. There are 5 points worthy of mention here, namely: 1. A special structure, microvilli polymerizing cisterna, is found on the tegument of 52-day-old Ms branche in all directions and a tubule like structure is connected to the matrix of the tegument. The significance of this structure may be dealt with the metabolism and transport of the parasite. 2. The tegumental spines appear on 52-day-old Ms. 3. The function of multilaminated vesicle in the tegument of 1-Ds may be associated with the turning over of the surface coat of the larvae and the compatibility between parasite and molluscan host. 4. Abundant alpha-glycogen granules and mitochondria appear in the cytoplasm of parenchyma cell of brood chamber of Ms and Ds. It is proposed that the parenchymal cells not only served as the filling material, but also serve as the nursing cells for the regulation of asexual reproduction of the sporocysts. 5. The orientation of muscle fibers of the head of the mi-Ds and narrow node region of 1-Ds shows a well development of the inner longitudinal fibers adjacent to the outer circular muscle layer. They run anteroposteriorly or vertically from the dorsal to the ventral. The pattern of muscle fibers may account for the activity of these regions of the parasite. (Figs 1-8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303342 TI - [Observation on ultrastructure of sterile cysts of Echinococcus granulosus in mice]. AB - The fine structure of sterile cysts of Echinococcus granulosus in mice was studied by TEM. The cyst wall consists of laminated layer and germinal membrane. At ultrastructural level, the laminated layer contains microfibrillate matrix and irregularly shaped electron-dense granules. The germinal membrane comprise of tegument and cell region. Plasmalemma invagination resembling the "pinocytotic vesicle" are seen between the microtriches of the tegument, and mitochondria are seen in the basal portion of the tegument. In the cell region, there are tegumental cells, muscle cells, and glycogen-containing cells. "Nucleolar channel system" can be observed in some of the glycogen-containing cells. PMID- 1303343 TI - [Preliminary observation of infectivity of isolated alveolar hydatid after cryopreservation]. AB - Alveolar hydatids of Echinococcus multilocularis obtained from the peritoneal cavity of mice were subject to freezing at -10 degrees C and -30 degrees C respectively. After 130-200 days' storage, the alveolar hydatids were transferred into the mouse peritoneal cavity for viability and infectivity testing. It was found that the alveolar hydatids stored at -10 degrees C were more severely damaged than those stored at -30 degrees C. The viability of the isolated alveococcus lasted half a year at -30 degrees C. PMID- 1303344 TI - [Observations on the long-term immune effect on healthy children of inoculating HB vaccine and the effect of a booster dose]. AB - This article reported the results of inoculating HB vaccine made in China into healthy children of O-1-2-month programme, under sero-epidemiological observation for 5 years. They showed that the highest peak of immunization was reached in the sixth month and then gradually diminished with the lapse of time until the 5th year when 74.1% of the immunized still had > or = 10 mIU/ml. That meant a good protective effect. Time of keeping anti-HBs had a direct bearing on the value of the highest period. According to the statistics it was told that. It took 6 years and 8 months for anti-HBs to fall below 10 mIU/ml. In the fifth year a booster lose was given with good response. An elevation of 12.1 times the previous immunizing level was observed, showing that a booster dose after 5 years of first dose of immunization was appropriate. PMID- 1303345 TI - [Aflatoxins and primary liver cancer--a population based case-control study]. AB - A case-control study of primary liver cancer (PLC) was conducted in 1989 at Fusui County, Guangxi Province. There were 99 PLC cases and 99 age-sex-residence matched controls. There were no difference of age, sex, race, cultural, level, marital status and annual income distribution (P > 0.05). The mean dietary AFB1 intakes of cases and controls were 117.72 + 105.68 mg/d, the mean outputs of AFM1 were 22.56 and 21.62 ng per morning urine respectively. The mean sera aflatoxin albumin adducts in both groups were 24.96 and 18.72 pg per mg albumin respectively. These indicators were of no statistical significance. Conditional Logistic regression showed that HBV infection (OR = 5.33), drinking pond-ditch water (OR = 3.70), family history of PLC (OR = 2.88), and total alcohol intakes (OR = 1.002) were statistically significant as risk factors (P > 0.05) rather than aflatoxins. This may be due to the fact that the samples selected in hyperendemic area both took high quantities of aflatoxin. PMID- 1303346 TI - [Lead concentrations in urine correlated with cytogenetic damages in workers exposed to lead]. AB - The lead concentrations in urine and the frequency of chromosomal aberrations and sister chromatid exchanges in lymphocytes of 84 printers exposed to lead were investigated. The results demonstrated that the lead concentrations in urine of printers were higher than normal subjects. The frequency of chromosomal aberrations and sister chromatid exchanges increased significantly with the rise of lead concentrations in urine, showing a linear correlation. The regression equations were Y = 1.31 + 9.07 X and Y = 4.24 + 14.91 X respectively. Therefore, the genetic condition of workers who have high lead concentrations in urine should be attended to and appropriate protective measures should be under-taken. PMID- 1303347 TI - [Effects of benzene on lipid peroxidation and the activity of relevant enzymes in human]. AB - Lipid peroxidation and the activity of relevant enzymes in workers exposed to benzene were measured. The results indicated that the content of serum malondialdehyde (MDA) increased while the activity of erythrocyte superoxide dismutase (SOD) and erythrocyte glutathione peroxidase (GSH-Px) decreased. The above changes were statistically significant as compared with the control group when the concentration of air benzene in the working environment was 50.21 mg/m3 and became more obvious with the increase of the concentration of air benzene. These changes occurred earlier, and more sensitively reflected the effect of benzene on human beings than changes of leukocyte and platelet counts. PMID- 1303348 TI - [Investigation on the immune function of coke-oven workers in a gas factory]. AB - This paper reports a study on the immune function of coke-oven workers in a gas factory. The results of immunological examination for coke oven workers exposed to pollutants from coal combustion showed that contents of lysozyme in the saliva, total complement and IgG, IgA in serum and T lymphocytes transformation activity in peripheral blood were all significantly lower than those in the control population. After the workers had separated themselves from heavy air pollution environment for 3 years, only the contents of lysozyme were higher than before, the other immune functions did not return to normal. PMID- 1303349 TI - [Study on the response index of population--the prevalence degree of pneumoconiosis]. AB - Comparison and analysis of the relationship between the prevalence and factors associated with CWP in five collieries, showed that the prevalence rate only reflected the rate of CWP in population and not the category construction of CWP; so, in certain circumstances, it is not suitable to estimate the risk of CWP in different collieries. A new index, the prevalence degree suggested by the authors, is a compound measure of risk of both the prevalence rate and the category construction of pneumoconiosis for population; so, it can reflect the risk of pneumoconiosis comprehensively and sensitively. PMID- 1303350 TI - [Studies on ozone toxicity and its environmental health criterion]. AB - The effects of ozone in low concentrations on animals and human beings were studied. The animal observations included biochemical tests, cellular analysis of bronchoalveolar lavage fluid (BALF) and blood, lung morphological observations by TEM and SEM. The human observations included pulmonary function test, behavior function test, etc. Through three years of study certain sensitivity indices and different threshold concentrations of ozone action have been found, and an environmental health criterion for ozone has been proposed, namely, the average concentration in one hour should not exceed 0.1 mg/m3. PMID- 1303351 TI - [The assay of beta-endorphin in some main foodstuff]. AB - The levels of beta-endorphin in autumn foodstuff of Shanghai local residents were determined with RIA. The results showed that the contents of -endorphins in aquatic products such as fish and prawn, etc. were higher than those in fowls. Certain foodstuff showed an increase of endorphin content after cooking. The content of beta-endorphin in egg was very small. The presence of beta-endorphins in foodstuff may be harmful to infants, small children and patients with increased gastrointestinal permeability. PMID- 1303352 TI - [Observations on the airborne fungi and their relationship to asthmatic patients in Shenyang Maluwan area]. AB - From July 1990 to June, observations were made of the type and amount of fungi present in the air, in the Maluwan District of Shenyang City, using dish-exposure and slide-exposure as method of detection. 954 colonies of fungi were isolated with dish-exposure, consisting of 47 species; and 11,033 fungi spores were collected with the slide-exposure. Skin tests were made using 13 species of fungi allergen for 114 cases of asthmatic patients, the positive rate was 73.7%. A special desensitization therapy was given to 103 cases of asthmatic patients, the total effective rate was 86.4%, while antiasthma drugs gave an effective rate of 41.1% (P < 0.01). PMID- 1303353 TI - [Research of disinfecting effect of SH-series (the equipment for secondary treatment of hospital sewage)]. AB - In order to examine the effect of using SH-series (i.e. The equipment for secondary treatment of hospital sewage) in treating sewage, we have been engaged in a series of testing-study. The results were as follows: The pollution of organic matter and microbes in hospital sewage was very serious. Both kinds of pollution were considered, when we plan our scheme of conducting hospital sewage treatment. The temperature of water was raised to 23.7-24.2 degrees C and the value of pH 7.4-7.8, the hospital sewage was treated for 60 minutes through the SH-series equipment with increased oxygenation and digestion the coliform group increased rapidly in geometrical progression. The reducing rate of the major organic matter pollution index was 69-89%. After having gone further through the SH-series treatment (Disinfecting and oblique-tubes sedimentation) sewage containing intestinal pathogens and tubercle bacilli reach the index comparable with GBJ48-83 (trial edition) "The standard". "The Disinfecting contacting time" was 1/4.5-1/2.2 of "The Standard", its "Residual chlorine" was 105-110% of "The standard". PMID- 1303354 TI - Dentine hypersensitivity: its prevalence, aetiology and clinical management. AB - Dentine hypersensitivity can be a frustrating condition to treat. The most common form of treatment is use of a desensitizing dentifrice, but for many patients this may provide only partial pain relief and recurrence is common. Recent research has provided several important findings which may serve as a basis for refining the approach to dentine hypersensitivity management, and for improving the success of treatment. This paper reviews the research and outlines a management system which transfers readily to clinical practice. PMID- 1303355 TI - A rationale for use of bases with amalgam restorations. AB - New lining materials has been developed from calcium hydroxide, zinc oxide eugenol and glass ionomers. This provides the dental practitioner with a wide choice of materials to use for protection of the pulpodentinal complex. In this paper their characteristics are reviewed and recommendations are made for their use. PMID- 1303356 TI - Repair of cleft lip and palate: 1. Surgical techniques. AB - Studies in Sri Lanka have demonstrated that in the absence of surgery, growth of the facial skeleton is normal. In developed countries, however, it is considered unacceptable to leave a child with an unrepaired cleft. The aim of surgery being to produce a near normal face. Part 1 provides an overview of the surgical repair of clefts and outline the general principles, as well as the most common surgical procedures. Part 2 will evaluate the surgical techniques and discuss the clinical research methodology involved. PMID- 1303357 TI - Prosthetic practice in the National Health Service: 2. Partial dentures. AB - This two-part series on the making of dentures in the National Health Service includes useful practical advice for the general practitioner. Part 1 discussed complete denture, whilst part 2 covers partial dentures. PMID- 1303358 TI - Government Dental Services in Sarawak, East Malaysia. AB - As part of the student elective, the author organized a small research project into Government Dental Services in Sarawak, East Malaysia. The resulting article gives an insight into dentistry in this country. PMID- 1303359 TI - Consent and the handicapped patient. AB - Changes in the care of handicapped people has resulted in them being more evenly distributed within the community. This increases the likelihood that they, or their carers, will seek treatment from general dental practitioners. It is, therefore, important to be aware of the regulations and forms involved in consent of a handicapped patient. PMID- 1303360 TI - Referral to hospital: improving communication between the dental practitioner and hospital dental staff. PMID- 1303361 TI - Nifedipine-induced gingival hyperplasia. AB - This case study reports on the management of a woman suffering from thrombocytopenic purpura who was referred to the periodontal clinic with gingival swelling and bleeding. This condition was related to nifedipine therapy for hypertension. PMID- 1303362 TI - Advances in fixed appliance design and use: 1. Brackets and archwires. AB - Many new developments in design and materials have made it easier for orthodontists to produce good result with fixed appliances in a shorter time. Orthodontic treatment has also become more comfortable and aesthetically pleasing for patients. This is the first of two papers which are intended to provide an update on fixed appliance design and use, so patients can be informed of relevant advances before they are referred to a specialist for orthodontic advice. Part 1 discusses the developments in brackets and archwires. Part 2 will cover recent advances in ligatures and elastomeric ties, intra-oral auxiliaries, adhesives, products to assist oral hygiene and prevention during fixed appliance treatment, and new methods of debonding. PMID- 1303363 TI - Matrices: their development and in clinical practice. AB - Recent developments in amalgam alloys composite resin materials have highlighted the importance of meticulous restoration placement by the dentist. This paper discusses the selection and use of the matrix which is significant in both the quality and longevity of the final restoration. PMID- 1303364 TI - Home bleaching. AB - In recent years the bleaching of teeth has become very popular. Bleaching regimes are based on the liberation of hydrogen peroxide at the tooth surface. The use of the bleaching products available in the UK as prescribed by a general dental practitioner appears to be valuable in the treatment of discoloured teeth if supervised by the practitioner, although a number of products have been released directly to patients. There is concern that these products are bought and used by patients without any professional supervision. PMID- 1303365 TI - Update on periodontology: 3. Initial preparation. AB - Over the last two decades there have been many changes in the basic concepts of periodontology, which have had profound effects on clinical practice. The aim of this series is to highlight the main areas of change to assist the busy GDP in staying up-to-date. Part 1 discussed current concepts in the histopathology of periodontal disease and part 2 looked at the problems of diagnosis. Part 3 will now examine the central role of plaque control in periodontics. PMID- 1303366 TI - Gingival Kaposi's Sarcoma: the first indication of HIV infection. AB - This article presents a case of gingival Kaposi's sarcoma that initially mimicked an acute periodontal infection, but was the first clinical sign of HIV infection in a 38-year-old male homosexual patient. The clinical features and treatment of oral Kaposi's sarcoma are discussed and the variable histopathology of the lesion is demonstrated. PMID- 1303367 TI - Dental care for elderly people with a handicap. AB - In the elderly population there is an increased incidence of impairment and disability, but these only become a handicap if the dental services fail to take them into consideration. This paper identifies the barriers and how they can be overcome. PMID- 1303368 TI - Communication, body language and dental anxiety. AB - Fear of dental treatment is commonplace in dental surgeries, and with more demands being made upon the dental team's already limited time, occupational stress has become more prevalent. Dentists should examine the various aspects of communication which will forewarn them of potentially difficult clinical situations, so that they can minimize the patient's anxiety and their own stress. PMID- 1303369 TI - Post-cure heat treatments for composites: properties and fractography. AB - Two commercial and four experimental composites were subjected to post-cure heat treatments of 10 min and 3 h duration immediately after light-curing. Fracture toughness, flexural modulus, microhardness and degree of conversion (FTIR) were evaluated 24 h later. The results showed that post-cure heat treatments at 120 degrees C of short or long duration can be used to produce significant improvements in the degree of cure and the mechanical properties of dental composites used as inlays. A 10 min heat treatment was as effective as a 3 h treatment in enhancing properties and degree of cure. In addition, a 3 h heat treatment carried out 7 days after the initial light-curing was capable of improving properties and cure to almost the same extent as the immediate heat treatments. The improvement in properties, in conjunction with the fractography, indicate a toughening of the filled resin matrix and possibly an improved filler/matrix adhesion in the microfills. The changes appear to be predominantly the result of an increase in degree of cure. PMID- 1303370 TI - A new light-activated adhesive cavity liner: an in vitro bond strength and microleakage study. AB - A new formulation of a light-activated calcium hydroxide-based cavity liner was developed for this study. Its shear bond strength and marginal microleakage in a Class V cavity preparation were compared to those of commercially available light activated liners and conventional glass ionomer liners: GC Lining Cement (GC), Ketac-Bond (ESPE), Time Line (Caulk), Vitrabond (3M), XR lonomer (Kerr), and Zionomer (DenMat). The new formulation had significantly higher shear bond strength to dentin than the commercially available materials. Its microleakage along gingival (cemento-dentin) walls was statistically equivalent to one of the other materials and significantly better than all the others. PMID- 1303371 TI - Post-irradiation polymerization of different anterior and posterior visible light activated resin composites. AB - The Knoop hardness number was measured for bottom and top surfaces of 2 mm thick specimens of different anterior and posterior visible light-cured composites. The variables for this study included various exposure times and a series of time intervals from immediately after curing up to 72 h. Post-irradiation microhardness at the bottom and top surfaces increased rapidly over the first hour, was slower during 24 h and showed no further increase after 24 h. Increasing exposure time resulted in higher microhardness values at both surfaces. Magnitudes of change were larger for the bottom surface. Exposure times longer than those recommended by the manufacturers were needed, especially for the anterior microfilled composites, to achieve adequately photo-activated resin that had an optimum bottom/top surface microhardness of 80-90%. Maximum hardness values were found to be dependent on the volumetric fraction but not on the average inorganic filler size. The post-irradiation increase in hardness value was independent of composite parameters and is probably commensurate with polymerization kinetics. PMID- 1303372 TI - Protection hypothesis for composite wear. AB - Significant occlusal wear occurs on posterior composite restorations in areas without direct contact with opponent teeth (contact-free wear) in addition to wear at the contacts. Recent research has indicated that all occlusal posterior composite surfaces wear, and those surfaces show decreasing wear rates over time. This provides more evidence for an earlier theory proposed by Jorgensen et al. (1979) that composite contact-free wear is a function of access and attrition caused by small particles in the food bolus. This hypothesis is now called the "protection theory" or "protection hypothesis" for wear. Macroscopic protection or "sheltering" from wear is provided by cavity preparation walls. Microscopic protection against resin matrix wear is provided by filler particles that are close together. Clinical evidence supporting the protection hypothesis comes from recently confirmed low wear rates for microfill and hybrid composites. The objective of this work was to calculate the minimum inter-particle spacing required for microscopic protection (wear resistance) for composites based on assumptions of packing fractions (0.68) with small particles (0.02 microns radius) for dispersed versus agglomerated conditions. An inter-particle spacing (IPS) of < 0.10 microns was assumed to afford wear protection. The results are that only 1.5-6.0 volume percentage microfiller is theoretically required to generate an IPS of 0.1 micron for composite microscopic protection. However, microfiller particles are suspected to agglomerate into clusters. Modified calculations for that effect indicate that at least 35% filler is required to provide microscopic protection. This effect explains much of the 3 to 5 year clinical research results for microfills and hybrids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303373 TI - A classification of dental composites according to their morphological and mechanical characteristics. AB - The on-going search for a biologically acceptable restorative material has brought a confusing variety of composites on the dental market. In the present study, commercially available composites are categorized as a function of their mean particle size, filler distribution, filler content, Young's modulus, surface roughness, compressive strength, surface hardness, and filler morphology. Out of this information, it can be concluded that the materials of choice for restoring posterior cavities at present are the Ultrafine Compact-Filled Composites because their intrinsic surface roughness, Young's modulus and, indirectly, their filler content, compressive strength, and surface hardness are comparable to the same properties of enamel and dentin. The Ultrafine Midway-Filled Composites seem to be very satisfactory materials for anterior use. PMID- 1303374 TI - The effect of ion strengthening time/temperature kinetics on the flexural strength of feldspathic porcelains. AB - The kinetics of ion exchange strengthening of three feldspathic porcelains were investigated. Data describing the effects of treatment time and temperature on flexural strength were produced. The temperature effect results support the hypothesis that the opposing phenomena of diffusion and relaxation control residual stress. The time effect results suggest that Fick's Law of diffusion and diffusional creep control flexural strength. Mechanisms were proposed. These findings suggest that precise control of temperature is more critical than control of time in this process of ion strengthening. Further investigations on the ion strengthening of low-fusing porcelains should be carried out. PMID- 1303375 TI - Effect of phenolic compounds on the polymerization of methyl methacrylate. AB - The inhibitory effects of six phenolic compounds and two analogues on the polymerization of methyl methacrylate (MMA) by azobisisobutyronitrile (AIBM) were examined. Differential scanning calorimetry was used to determine the induction period (IP) and initial rate of polymerization (IRP). The IP values (minutes) decreased in the order: eugenol > thymol > hydroquinone > cresol > guaiacol > phenol >>> safrole > methol. The IRP values of all compounds tested ranged from 0.8 to 1.2 percent per minute, except for hydroquinone (0.2 percent per minute). Phenolic compounds inhibited the polymerization of MMA by scavenging radicals, and eugenol was the most potent inhibitor. PMID- 1303376 TI - Effect of tooth storage and cavity cleansing on cervical gap formation in Class II glass-ionomer/composite restorations. AB - Class II cavities with the cervical margin just below the C-E junction and with two cervical retention grooves were prepared in intact human premolars, 31 cavities in teeth stored frozen and 29 cavities in teeth stored in 1% chloramine solution. The teeth from both storage conditions were assigned to two groups; in one group, the cavities were cleaned with a water spray, in the other group, with a cleaner containing 0.2% EDTA and 1% NaF. All cavities were lined with Vitrebond and restored with P50. Cervical contraction gaps were disclosed by a fluorescent resin penetration technique. The length and width of each gap were analysed. A contraction gap was revealed in 17 of the 31 cavities in teeth stored frozen (54.8%) and in 22 of the 29 restorations in the teeth stored in chloramine (75.8%). The width of the gap was significantly greater in teeth stored in chloramine (p = 0.0004). No statistical difference in gap formation was found between cavities cleaned with water or with the detergent containing 0.2% EDTA and sodium fluoride. Since the cavity cleansing procedure was not a significant factor in gap formation, apparently removing the superficial smear layer with the cavity cleaner does not impair the bonding of Vitrebond to the dentin. However, gap formation appeared to be significantly affected by the storage conditions of the extracted teeth. It is suggested that teeth to be used in bond strength and leakage experiments should be stored frozen rather than stored in 1% chloramine solution. PMID- 1303377 TI - Load dependency and reliability of microhardness measurements on acid-etched enamel surfaces. AB - The load dependency of hardness measurements was investigated on sound and demineralized enamel samples. For all samples investigated, the Knoop hardness number (KHN) varied as a function of the applied load. Higher loads enhanced indenter penetration into the test surface. The variation in KHN values observed in demineralized enamel, both surface-softened and surface-etched, was explained by a decrease in porosity as a function of depth. The reading error for indentations made on surface enamel etched with 37% phosphoric acid gel for 30 s was found to be slightly elevated compared to indentations made on a polished sound enamel surface. It was concluded that the surface microhardness technique can be used for the longitudinal investigation of etched surface enamel. PMID- 1303378 TI - In vitro vibrational wear under small displacements of dental materials opposed to annealed chromium-steel counterbodies. AB - In vitro vibrational wear tests were performed on 17 composites and one amalgam with human enamel as a reference. The specimens were fixed on a computer controlled X-Y translation table that generated an oscillatory movement under small displacements. The dental material specimens were in permanent contact with an annealed chromium-steel counterbody. The tests were performed in ambient air of normal humidity at room temperature under non-lubricated sliding conditions. The friction between the counterbody and each of the various materials was measured on-line. After completion of the tests, the wear volumes were determined by contactless profilometry, and the wear pattern was studied with SEM. The simple vibrational test used in this study allowed a fast classification of different dental materials in terms of the relative wear on either the specimen or the counterbody material. The ratio of the wear volume of the counterbody versus the wear volume of the dental material specimen was used to accurately classify the materials according to their in vitro wear behavior, especially when this ratio was related to the total wear volume of the dental material specimen and the counterbody. From an analysis of the wear behavior of the both contacting materials, it became obvious that neither the wear of the dental materials nor of the chromium-steel counterbody appears to correlate with either the inorganic filler hardness, the intrinsic surface roughness, the surface hardness or the Young's modulus of the dental materials. PMID- 1303379 TI - Synthesis and polymerization of new expanding dental monomers. AB - The objective of this work was to develop polymeric materials that expand slightly upon polymerization and that could potentially be used as matrix resins for dental composites. A series of stereoisomeric alicyclic spiroorthocarbonates (SOC's) that expand when polymerized were synthesized. Three of these SOC racemates were analyzed: cis/cis-, cis/trans- and trans/trans-2,3,8,9 di(tetramethylene)-1,5,7,11-tetraoxaspiro[5.5] undecane. The degrees of expansion, approximately 3.9% and 3.5%, for the cis/cis and trans/trans, were determined by measuring the specific volume of the monomers and polymers in dilute solutions. This method of determining densities and subsequent calculated expansion or shrinkage was validated by duplicating the reported shrinkage of 4 tert-butylphenyl glycidyl ether, styrene, and methyl methacrylate. Based on these data and spectral data obtained using other analytical techniques, these stereoisomeric alicyclic SOC's appear to have potential as nonshrinking polymer or copolymer matrices for dental composites. PMID- 1303380 TI - Effect of water-soluble photoinitiator on the adhesion between composite and tooth substrate. AB - The effectiveness of a water-soluble photoinitiator in a dentin primer was examined by measuring the tensile bond strength between the composite and tooth substrate treated with the primer. The water-soluble photoinitiator, 2-hydroxy-3 (3,4 dimethyl-9-oxo-9H-thioxanthen-2-yloxy)-N,N,N-trimethyl-1- propanaminium chloride (QTX) was dissolved into an aqueous solution of methoxy nonaethyleneglycol monomethacrylate (M9G) or poly-N-vinylpyrrolidone (PNVP), and these aqueous solutions were used as primers. The combination of 0.5 M EDTA pretreatment and 1% QTX -35% PNVP aqueous solution priming produced the highest bond strength. A mixture of dentin fractures and interfacial failure between the dentin and the resin was observed in the test specimen. This dentin priming combination was also effective in improving the bond strength to enamel pretreated with EDTA. PMID- 1303381 TI - Surface properties and castability of elastomeric impression materials after plasma cleaning. AB - The wettability of impression materials is an important requirement for accurate reproduction of intraoral structures. The aims of this study were to evaluate the effect of plasma cleaning on critical surface tension and die stone castability of five silicone impression materials. Critical surface tension was calculated using a contact angle analysis according to Zisman (1964), before and after plasma cleaning. Die stone casts were produced from impressions of a master die and the area extension of the reproduction was measured planimetrically. The results showed a general increase in the critical surface tension and in the polar force component of the composite free energy for materials treated with plasma cleaning. An improvement in castability of all materials was also noted. PMID- 1303382 TI - Environmental hazard evaluation of amalgam scrap. AB - Amalgam scrap was subjected to two different Environmental Protection Agency (EPA) extraction procedures to determine if it presents an environmental hazard. The results indicate that concentrations of mercury and silver in the extracts do not exceed the EPA's maximum allowable concentrations. It was concluded that amalgam scrap is not a hazardous solid waste. Proper handling of amalgam scrap disposal by recycling is, however, highly recommended. PMID- 1303384 TI - Effect of admixed indium on properties of a dispersed-phase high-copper dental amalgam. AB - A new dental amalgam alloy containing admixed indium is available for clinical use. The purpose of this study was to conduct a full range of laboratory tests on two alloys containing differing amounts of admixed indium and on a similar alloy that did not contain indium. Results showed that less mercury was required to mix the alloys containing indium since admixed indium promotes wetting of the alloy. Back-scattered electron images showed the Ag-Hg matrix to be in good apposition to the Ag-Sn particles and to the Ag-Cu eutectic spheres, and there was no evidence of unreacted indium. The alloys containing admixed indium demonstrated improved resistance to creep and very little dimensional change upon setting. The early compressive strength was low for the alloys containing indium, but compressive strengths were significantly higher than those of the alloy without indium at 24 h and 7 d. Some improvement in resistance to marginal leakage and to corrosion was shown for the alloys containing indium. PMID- 1303383 TI - Evaluation of new methods for composite repair. AB - This study evaluated the effectiveness of air abrasion (sandblasting), hydrofluoric acid (HF) etching, and acidulated phosphate fluoride (APF) for composite repair. Five different composites (three hybrids, one small-particle, and one microfill) were used to test the effects of different compositions and particle sizes. A phosphonate resin bonding agent was used for all repair procedures. In general, air abrasion provided the strongest repairs, approximately 60% of cohesive strength. The effect of HF varied with different composites, either improving or reducing the repair strength. APF gave the lowest interfacial bond strengths for all composites except the microfill. PMID- 1303385 TI - Shear bond strengths of ten dentin adhesive systems. AB - This in vitro study tested the shear bond strengths of nine third-generation dentin bonding systems. All of these systems had higher bond strengths than the control, a second-generation agent. Amalgambond and All-Bond had the strongest bonds to dentin, 23.3 +/- 5.7 and 19.3 +/- 5.6 MPa, respectively. Clearfil Photo Bond and Prisma Universal Bond 3 had intermediate bond strengths (approximately 13 MPa). Gluma, PowerBond, Scotchbond 2, Tenure, and XR-Bond all had mean shear bond strengths of less than 8 MPa. PMID- 1303386 TI - [The economic consequences of breaches of hygienic standards]. AB - Economic detriment due to the main occupational diseases diagnosed in 1990 forms a sum of 2.58 billion roubles. Careful assess of economic losses concerning only a deficiency in supply due to an increased morbidity of workers gave a total amount of 20 billion roubles a year in prices of 1987. Privilege pensions connected with hazardous working conditions and based on lists N1 and 2 are considered as an occult legalization of the hygienic norms breaking. Contents of the lists trend to expand. By the end of 1987 the privilege pensions payments covered 6.6 billion roubles, but in 1991 that sum reached 7.3 billion roubles. PMID- 1303387 TI - [The physiological mechanisms of the adaptation of metal workers to exposure to elevated convection and combined radiant and convection heat]. AB - Metallurgists exposed to exceeding amounts of radiant heat and convection heat combined with the radiant one demonstrate such general physiologic adaptational mechanisms as: reflectory tachycardia, intensive sweating, heat conducting to the skin surface of the body, abruptly increased minute respiratory volume and possible filtrative sweating. Furthermore heavy physical work induced the extremely abrupt tachycardia, the increased systolic and pulse pressure, systolic and cardiac output, total ventilation per minute. The recommendations were suggested to prevent overheating in workers. PMID- 1303388 TI - [Temporary work incapacity in the workers of the heat-treatment shops of the metallurgical industry due to diseases of the digestive system]. AB - Transitory disablement in 5886 workers engaged for the whole year into heat treating metallurgy was compared during 5 years (1981-1985) with that in 291 workers engaged into repairing mechanical occupations so as to reveal metallurgical occupational factors influencing on gastrointestinal morbidity. Metallurgical occupational hazards harm the health status in workers engaged into heat-treating metallurgy, induce the gastrointestinal disorders, which are demonstrated by the elevated transitory disablement. The workers engaged into heat treating metallurgy showed higher gastrointestinal morbidity rate than those engaged into repairing mechanical work. PMID- 1303389 TI - [Occupational morbidity in the workers of metallurgical enterprises]. AB - Occupational morbidity was analysed in workers of 15 metallurgical enterprises according to the enterprise profile, worker's age, sex, length of service and occupation. The analysed data are represented in the article, the measures are recommended so as to reduce the occupational morbidity. PMID- 1303391 TI - [The metabolic interaction of cobalt and silver in the body during their combined action]. AB - Mixtures of cobalt and silver in ratio (0.2:0.4), (0.2:0.2) and (0.2:0.1) mg/kg were once administrated intraperitoneally and intratracheally to white rats. Metabolism of the metals was studied. Combined exposure to metals appeared to influence greatly on their toxicokinetics. The co-action between metals appears during their absorption into the blood--the elevated peritoneal absorption of cobalt depresses that of silver. The reverse relationship is demonstrated during the intratracheal insertion. Such peculiarities of co-action exist during the further stages of metabolism. PMID- 1303390 TI - [Respiratory disease morbidity in workers in ferrovanadium production]. AB - Links between the occupational factors of iron-vanadium production and respiratory morbidity in workers are revealed in the article. The work conditions of such occupational groups as preparatory workers (preparing and splitting of a furnace charge, slag grinding), roast workers, hydro- and electric metallurgy employees are evaluated by hygienic methods. Structure, relative risk and the standardized risk of respiratory diseases formation were shown in different occupational and age groups. PMID- 1303392 TI - [Individual protection aids for saving people during a fire]. AB - All existing individual protective means can not be applied to the life saving and the mall evacuation of people from fire due to their technical complexity and inadequate protective efficiency. The research work carried out by the authors served to produce a crucially new type of physiologically acceptable individual protective means against burning products and high environmental temperature. PMID- 1303393 TI - [The effect of working conditions on the physiological functions of operators engaged in natural gas recovery in Uzbekistan]. AB - Work conditions and professional activities were examined in 39 gas extracting complex operators at the age of 30-45, exposed to high environmental temperatures during more than 3 years. It became particularly evident that the observed changes of functional status in the operators were due to fatigue caused by occupational factors and professional peculiarities. Measures are suggested to normalize the hygienic parameters of the working environment and organize the work. PMID- 1303394 TI - [The possibility of using computed tomography in the diagnosis of silicosis and silicotuberculosis]. AB - Potentials of computed tomography application to occupational pulmonology are not identified yet, hence it has a limited utility in this sphere. Computed tomography combined with roentgenologic methods serves to specify the origin and size of affected mediastinal nodes, to distinguish between silicotic and silicotuberculotic affects and nodules. Additional data are required. PMID- 1303396 TI - [The spectrophotometric determination of vinylimidazole and benzvinylimidazole in the air of a work area]. AB - A spectrophotometric method of vinyl-imidazole and benzo-vinyl-imidazole detection in the air of working area is worked out. The method is based on the vinyl oxidation into formaldehyde and the detection of latter by reaction with sodium bichromotropate. The optic density is measured at 580 nm. PMID- 1303395 TI - [Photometric and chromatographic methods of measuring the concentration of acelysin in the air of a work area]. AB - Two methods were applied to evaluation of acelysine level. Spectrophotometric one was based on reaction with p-nitrophenyldiasonium and evaluation of the product optic density at 510 nm. The second was chromatography in thin layer, where a mixture of n-butanol, formic acid and water was used as an eluent and 0.2% ninhydrin solution in butanol and 3 ml of ice acetic acid (60-70 degrees C) served as a developer. Both methods are supposed to evaluate acelysine level in the air of working area, when a half of MAC and admixtures are present. PMID- 1303397 TI - [The reference safe exposure levels (RSEL) of harmful substances in the air of a work area approved in 1991]. PMID- 1303398 TI - [The establishment of the MPEL for impulse noise]. AB - A total of 328 blacksmiths was examined so as to obtain and analyse the physical parameters of noise exposure for its hygienic evaluation and norm setting. The noise parameters were found to vary according to different criteria if underassessed by means of existing standard 3223-85. Comparative study of hearing loss in the blacksmiths according to a standard 1999 revealed a hyperaggressiveness of impulsive noise in close connection with both noise level and length of service. Impulsive noise was recommended to be evaluated according to the peak level and quantity of impulses, but the basement of MAL is possible with the help of standard pattern while the criteria as length of service, quantile of population and the grade of hearing loss are chosen. PMID- 1303399 TI - [An automated system for maintaining the concentration of a dusty environment in an inhalation chamber]. PMID- 1303400 TI - [The physiological hygienic assessment of the assembly operations in automobile manufacture]. PMID- 1303401 TI - [The working conditions during the prototype commercial operation of continuous output equipment in KATEK coal stripping and sanitary improvement measures]. AB - Work conditions were analysed in workers engaged into realization of the new coal extracting line technology producing 5250 m3 of coal per hr in KATEK open-cast mine. Hygienic standards appeared to be followed mainly on the constant working places and in the mining machine cabs, but noise dust parameters were not evaluated in the transloaders, microclimate parameters of excavator and transloaders were not assessed during the cold season. High concentration of dust appear in the air due to mining machines cleaning with the pumped air. Workers engaged into the coal transportation and its intermediate storage appeared to work in more hazardous conditions. Sanitary measures are suggested. PMID- 1303402 TI - The use of bone grafting materials in implant surgical applications: Part 1. PMID- 1303403 TI - Americans with disabilities-deaf/hearing impaired patients. PMID- 1303404 TI - Common investment planning mistakes. PMID- 1303405 TI - Geriatric services--need of the hour. PMID- 1303406 TI - Colloidal bismuth subcitrate in non-ulcer dyspepsia. AB - The effect of colloidal bismuth subcitrate (De-Nol) on symptoms, Helicobacter pylori status and histological features was studied in 35 patients with non-ulcer dyspepsia. Pain (34 cases) and gas bloat (18) were the predominant symptoms. H pylori was present in 26 (74.3%) patients. Gastritis and duodenitis were present in 29 of 32 and 22 of 31 cases respectively in whom biopsies were available. Relief in symptoms after treatment was seen in 29 (82.8%) cases. Improvement in gastritis and duodenitis was noted in 60.8% and 58.8% respectively; over 70% of H pylori positive patients cleared the organism. These changes did not correlate with the relief in symptoms. We conclude that colloidal bismuth subcitrate is effective in the short term treatment of non-ulcer dyspepsia. It also clears H pylori infection and results in improvement of histological features. PMID- 1303407 TI - MURCS association--a review of 7 cases. AB - MURCS association (Mullerian hypoplasia/aplasia, renal agenesis and cervicothoracic somite dysplasia) is emerging as the second most frequent cause of primary amenorrhoea after Turner syndrome. Seven cases have been described and analysed. All cases had absence of uterus and tubes 85% had cervical spine abnormalities such as vertebral fusion, hypoplasia of vertebrae or butterfly vertebrae and short stature and 28% had renal agenesis or ectopy. The latter finding is in contrast to the reports in world literature where the frequency of renal agenesis is higher. There was no familial incidence in these seven cases lending credence to the belief that the association is essentially sporadic. PMID- 1303408 TI - Hyperbaric oxygen therapy in diabetic foot. AB - To study the effect of hyperbaric oxygen therapy in chronic diabetic foot lesions, a prospective controlled study was undertaken. Thirty diabetics with chronic foot lesions were randomised to study group (conventional management and 4 sessions of hyperbaric oxygen therapy) and control group (conventional management). The patients were assessed for average hospital stay, control of infection and wound healing. The control of infection spread was quicker. Positive cultures decreased from initial 19 to 3 in study group as against from 16 to 12 in the control group. (p < 0.05). This difference was most pronounced for Escherichia coli. Also, the need for major amputation was significantly less in the study group (n = 2) as against the control group (n = 7) (p < 0.05). The average hospital stay was not affected. We conclude that hyperbaric oxygen therapy can be safely used and is beneficial as an adjuvant therapy in chronic diabetic foot lesions. PMID- 1303409 TI - Role of ultrasonography in early pregnancy complications. AB - Two hundred patients in the first trimester of pregnancy presenting with complications were evaluated both clinically and by ultrasonography. The ultrasonographic interpretations were classified as either confirmatory, diagnostic or misleading based on their correlation with the clinical diagnosis. It was observed that in 51% cases sonography was confirmatory, in 41% diagnostic and in 8% misleading. Used judiciously, ultrasonography provides a reliable aid in management of early pregnancy complications. PMID- 1303410 TI - Changes in thyroid hormones in surgical trauma. AB - A prospective study of 20 patients who underwent elective surgery, is presented reporting the effect of surgical trauma on circulating thyroid hormone levels. Although no increase in the serum T4 levels was observed following surgery, serum T3 values were found to decrease and serum rT3 values were found to increase in the post-operative period, representing activation of an alternate pathway in the peripheral conversion of T4 to T3. Since trauma induces a hypermetabolic state due to hypersecretion of cortisol, alterations in thyroid hormone levels were concluded to represent an appropriate response in trauma to counter the effects of trauma-induced cortisol hypersecretion. PMID- 1303411 TI - Experience with the pectoralis major myocutaneous flap for head and neck reconstruction in a general surgical unit. AB - The pectoralis major myocutaneous (PMMC) flap or its modification was used in 19 cases after resectional surgery for malignancy of the oral cavity with minimal morbidity and no mortality. The resection as well as reconstruction was done by the same team consisting only of general surgeons. The final functional and cosmetic results were satisfactory. The pectoralis major myocutaneous flap is a hardy flap and can be performed with relative ease even by those not specialised in plastic surgery. This makes it an important tool for a general surgeon practicing in a country like India with its high incidence of head and neck malignancy. PMID- 1303412 TI - Effect of ipratropium bromide in bronchial asthma. AB - The effect of inhalation of ipratropium bromide was evaluated in 20 patients with bronchial asthma. It was observed that there was no significant improvement in the forced vital capacity and the forced expired volume in one second, while there was significant improvement in the peak expiratory flow rate (PEFR) measured at 9 pm, after inhalation of 2 puffs of ipratropium bromide aerosol (0.02mg/puff) three to four times a day for 2 weeks. Since PEFR is a measure of large airway function and cholinergic mechanisms are primarily involved for airflow obstruction at large airways, improvement in PEFR by ipratropium bromide highlights its role as a useful bronchodilator in patients in whom vagal reflexes are responsible for the provocation of bronchoconstriction. PMID- 1303413 TI - Congenital leukemia--organ involvement in six autopsy cases. AB - Six cases of congenital leukemia were encountered in pediatric autopsies carried out over a period of 7 years. The postmortem findings of these cases were analysed and presented along with antemortem peripheral and bone marrow smear. All the cases were diagnosed as acute myeloid leukemia. Gross changes were observed in lungs, liver, spleen and kidneys. Histological abnormalities were detected in these organs as well as the heart, pancreas and intestine. Lymph node follicles were well preserved in all. The thymus showed a normal lobular pattern with interstitial infiltrate. Bone marrow showed myeloid blast cells with depletion of the erythroid and megakaryocytic cells. PMID- 1303414 TI - Bio-availability and drug delivery systems: clinical perspective. PMID- 1303415 TI - Melanocytoma of the optic disc. AB - Melanocytoma of the optic disc is a benign lesion. We report here a patient with melanocytoma who presented with gradual diminution of vision. On examination the left eye fundus showed a mass uniformly dark black in colour, on the optic disc occupying the superotemporal quadrant. The mass completely obscured the fluorescence on fluorescein angiography and was thus differentiated from malignant melanoma. PMID- 1303416 TI - Female circumcision: a risk factor in postpartum haemorrhage. AB - A major postpartum haemorrhage occurred in a patient with a previous history of female circumcision. Following assisted vaginal delivery 6 litre blood loss occurred as a result of tears to the vagina and perineum. The tears were sutured, followed by insertion of vaginal packs. Replacement fluid therapy was given. To reduce the incidence of tears and accompanying haemorrhage, it is advisable to perform two episiotomies viz. anterior and midline posterior or mediolateral. PMID- 1303417 TI - Laser in the management of stenosing oropharyngeal scleroma. AB - We present here our experience of laser for the management of stenosed oropharyngeal scleroma. The diagnosis of scleroma was made 14 years ago and the patient underwent repeated procedures like dilatation, diathermy excision of adhesions and cryosurgery during this period. He attended our out-patient department with complaints of dysphagia and difficulty in breathing, progressing to stridor. On examination, severe oropharyngeal stenosis due to cicatrization extending between the base of the tongue and the post-pharyngeal wall was seen. Using CO2 laser, cicatrix was released by making radial cuts and the oropharyngeal opening was widened. No tracheostomy was needed; no blood loss occurred and the patient was discharged on the next day. PMID- 1303418 TI - Pathological rupture of malarial spleen. AB - Two cases of spontaneous rupture of malarial spleen are reported here. One of them was a male who was on chloroquine for an acute attack of malaria. While on therapy, he complained of pain in left hypochondrium followed by palpitations. The other patient was a female who was admitted for continuous dull aching pain and fever. In both the patients, exploratory laparotomy revealed an enlarged spleen with tear. Splenectomy was performed. Histopathological examination revealed dilated congested sinusoid with follicular atrophy, and RBCs with malarial parasites. The post-operative course was smooth in both patients. PMID- 1303419 TI - Isolated posterior dislocation of the radial head in an adult. AB - Isolated posterior dislocation of the radial head was detected on X-ray in a patient following a vehicular accident. Such a dislocation without an associated fracture is extremely rare in adults. Immobilization of the elbow in full pronation and 90 degrees flexion for 4 weeks normalized the position of the head of the radius. PMID- 1303420 TI - Facial nerve involvement in pseudotumor cerebri. AB - A woman with history of bifrontal headache, vomiting and loss of vision was diagnosed as a case of pseudotumor cerebri based on clinical and MRI findings. Bilateral abducens and facial nerve palsies were detected. Pseudotumor cerebri in this patient was not associated with any other illness or related to drug therapy. Treatment was given to lower the raised intracranial pressure to which the patient responded. PMID- 1303421 TI - Nonfunctioning adrenocortical carcinoma. AB - The rarity of adrenocortical carcinoma prompted us to report a case who came with a history of swelling in the left flank associated with pain, weakness and loss of appetite. Ultrasonography revealed a left retroperitoneal mass which was removed by radical surgery along with the left kidney and spleen. On histopathological examination, a diagnosis of adrenocortical carcinoma was made. (Hough criteria score 2.97). The cells of the tumor were arranged in closely packed columns and cords supported by fibrovascular stroma. There was no evidence of metastasis. PMID- 1303422 TI - Asymmetric crying facies: the cardiofacial syndrome. AB - A 5 1/2 month old female child presented with cyanosis and recurrent respiratory infection. Asymmetric facies was noticed on crying. On investigation an ostium secundum atrial septal defect with right partial anomalous pulmonary venous connection and severe pulmonary hypertension was detected. The association of asymmetric crying facies with congenital cardiac anomalies, known as cardiofacial syndrome, is presented here to highlight the use of this clinical sign as a marker to congenital anomalies. PMID- 1303423 TI - Leiomyoblastoma of the stomach. AB - A case of gastric leiomyoblastoma in a 37 year old male is presented. The patient presented with 3 episodes of melaena requiring blood transfusion on one occasion. There was no associated haematemesis, abdominal pain, obstruction or a palpable lump. The tumor was sessile and completely intraluminal with superficial ulceration displaying distinctive histologic features. Seven years after partial gastrectomy the patient has remained asymptomatic. PMID- 1303424 TI - Percutaneous balloon mitral valvuloplasty. PMID- 1303425 TI - Medical education--are we on the right tract? PMID- 1303426 TI - [Toxicology in legal medicine]. AB - The purpose of toxicology in legal medicine is to determine the presence of chemicals effecting the human body in biological samples and to interpret the concentrations of chemicals. Analytical methods and medico-legal interpretations of the results of poisoning cases were discussed. 1. "Yusho," PCB poisoning "Yusho" was determined to be PCB poisoning by the detection of PCB in Rice-oil used by a "Yusho" family. My toxicological works were based on the study of "Yusho," which taught me the importance of the collaboration between faculties, the moral of the co-worker, and the PCB contamination in the laboratory. 2. Drugs In order to interpret the concentration of bromvalerylurea in blood, a very sensitive method was developed using a Florisil mini-column for cleaning up, and ECD-GC for analysis. GC/MS is used to determine the concentrations of other drugs in biological samples as well. 3. Pesticides In the first case of fatal ethyl parathion poisoning, only ethyl parathion in the stomach contents was analyzed by ECD-GC, and the cause of death was determined to be ethyl parathion poisoning. In the second case, parathion in the blood, brain, and stomach contents was analyzed. Both cases, however, were not reported in detail in the journal. Joint study on pesticides with the Division of Emergency Medicine is carrying on now. 4. Thinner Male rats were exposed to toluene vapor in pure oxygen, air, and 10% O2 air. Anesthetic death from thinner vapor was confirmed. It seems that inhalation of toluene in a hypoxic atmosphere, such as from a plastic bag, is very dangerous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303427 TI - [Medical education reviewed by legal consultation of civil affairs]. AB - I pointed out the following medical problems based on my own research and investigations of civil proceedings relating to accidents. 1. Pay little attention to the circumstances of the accident 2. Too much emphasis on laboratory investigations for medical diagnoses 3. Unsuitable medication or medical examination 4. Money-making medical care and treatment 5. Poor mental care 6. Unsuitable or incorrect descriptions of the medical conditions of the subject 7. Lack of moral sense 8. Lack of ability to guide the co-medical staff Pre and post graduate medical education must be improved and as forensic pathologists we have to participate in finding a solution for these problems. Now is the time to reform the medical system and the cost of medical examination, treatment and consultation. PMID- 1303428 TI - [Molecular biological studies on teeth inquests]. AB - This paper deals with the following three areas: 1. Age estimation of tooth based on the racemization of component amino acids On the age estimation of a subject's tooth, the whole dentin prepared from the central vertical section showed a correlation coefficient of more than 0.99. The soluble peptide extracted from the dentin provided the highest correlation compared with the total content of amino acids or insoluble collagens, suggesting its usefulness as a component for estimating the age. The racemization rate was the highest for Asp, followed by Glu and Ala in order. As to the site from which a test dentin is sampled, the ratio of Asp from the lingual section was higher than its counterpart from the labial section. It is also noteworthy that the dentin from deciduous teeth was as useful as the permanent teeth for estimating the age of juvenile. 2. DNA typing analysis using tooth as specimen The pulp in a dried tooth is removed, from which DNA in extracted for DNA fingerprinting with the Y-specific probe. The sex determination was possible using a tooth that had been extracted up to 21 months before. Furthermore, a 30-cycle repetition of PCR enabled to accurately determine the sex from the DNA specimen that was considerably degraded as well as from freshly sampled DNA. 3. Inspection by dentists The dental and roentgenographic records provided by the families allowed rapid personal identification in major disasters, traffic accidents, fires etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303429 TI - [Forensic autopsy--anatomical diagnosis of asphyxial death]. AB - In hospital cases, since a clinical history is usually present and the cause of death suspected, the chief duty of the pathologist is to describe and study the pathologic conditions revealed by his dissection. In medicolegal cases, the forensic pathologist must determine the cause of death and the circumstances of death, without any clinical history or clue to guide him except the lesion of trauma or disease which he discovers post mortem. The recognition of asphyxia as a cause of death at autopsy is occasionally difficult and requires considerable care, skill and understanding based on experience of the forensic pathologist. When a mechanical asphyxial death is suspected, the following method is a convenient routine procedure in our laboratory. 1. External Examination A systematic and careful examination of the external feature is made. 2. Internal Examination A "U" shaped incision is the most satisfactory method to inspect the internal tissues of neck in situ. 3. Laboratory Investigation The tissue examined routinely under the microscope are cervical lymph node, tongue, carotid body, lung, cortex of brain and skin. The heart's blood is collected to examine the fibrinolytic factors and thyroid hormones. PMID- 1303430 TI - [What histology is normal and abnormal in the liver?]. AB - Normal and abnormal morphologies of the liver were histopathologically reviewed. Characteristic structure and specialized functions of the liver, and the age and life style of the patients should be taken into consideration of the evaluation of abnormal liver morphologies. The latter were generally classified into pathologic changes, nonspecific and non-significant findings, agonal changes and postmortem changes. Pathologic changes were subdivided into several categories according to their pathogenesis and etiologies. While postmortem changes lack of vital reaction, apoptosis, a programmed cell death, is also lacking inflammatory reaction. These findings should be comprehensively analyzed in the pathologic evaluation. PMID- 1303431 TI - The value of bacteriological investigations within the scope of forensic autopsies--the toxic shock syndrome (TSS) in humans. PMID- 1303432 TI - Pathophysiology of hypoxia: findings focused on pulmonary surfactant. PMID- 1303433 TI - Medicolegal diagnosis of asphyxia--cerebral blood flow and brain oxygen tension. AB - Over the last several years, using rabbit models the authors analyzed cerebral blood flow (CBF), the brain oxygen tension (PtO2) and other physiological parameters during asphyxiation as means of achieving a practical diagnosis of asphyxiation. The author reports here on the effects of compression of the carotid arteries and obstruction of the airway leading to hypoxia, based on an analysis of CBF and PtO2 during hanging. Immediately after hanging, the CBF dropped but then rose suddenly. After several minutes, it dropped along with blood pressure. The PtO2 continued to decrease until the time of irreversible apnea. These findings suggest the effects of compression of the carotid arteries and the airway occlusion. After death, these results were confirmed with the injection-molded resin specimens of the airway and by the angiograph. But the closure of the vertebral arteries was not produced by the hanging. PMID- 1303434 TI - The course of respiration and circulation in death due to various types of asphyxia. AB - To investigate the course of respiration and circulation in death due to various types of asphyxia, dogs were asphyxiated by a method simulating typical hanging, by plastic-bag suffocation, by breathing pure nitrogen and low concentration of oxygen. Intrathoracic pressure, blood pressure in the femoral artery, electrocardiogram and electroencephalogram were registered and were compared with the course in death due to obstructive asphyxia. PMID- 1303435 TI - Application of hemoglobin analysis by CO-oximeter to medico-legal practice with special reference to diagnosis of asphyxia. AB - Hemoglobin analysis by CO-oximeter is more easily and rapidly available method than other spectrophotometric or GC methods. In the present study, the possibility of diagnosis of asphyxia by CO-oximeter was examined experimentally using rabbits. When measured value of oxyhemoglobin (O2Hb) was lower than about 20% and that of deoxyhemoglobin (HHb) was, on the other hand, higher than about 80%, being accompanied by low measured values of both methemoglobin (MetHb) and CO-hemoglobin (COHb) (< 5%), asphyxia should be firstly considered as the cause of death. To the corpses found at the scene of fire, three chief factors causing death such as burns, suffocation due to oxygen deficiency and intoxication by poisonous gases may have occurred simultaneously, and through measuring the values of O2Hb, COHb, MetHb and HHb, the main lethal factor could be selected out among these three factors above and the cause of death could be examined much more closely. Because of easy and rapid analysis, it could be considered that CO oximeter was useful for forensic practices and police activities. PMID- 1303436 TI - Fire death and hypoxic death. AB - Participation of hypoxic hypoxia in low COHb (Carboxyhemoglobin) concentrations frequently observed in fire victims was examined using rats and rabbits exposed to low-O2 and CO gas mixtures. Rats exposed to the most hypoxic gas mixture (O2 3%-CO 0.3%) died with COHb value below 40%. Rabbits also died with a low COHb concentration under this condition, but the COHb concentration was not below 50%. From the literature as well as the findings obtained in the present experiment, hypoxic hypoxia did not appear to be a main factor causing death at low COHb concentrations. PMID- 1303437 TI - Re-evaluation of death by asphyxia based on cerebral blood flow (VII)--on the information on electric potentials obtained from deep electroencephalographic electrodes. AB - The author presents electroencephalographic patterns (a physiological parameter of the brain function observed at rapid and fatal drowning of rabbits), cerebral blood flow (CBF) which support the physiological activities of the brain, and the relationship between systemic respiration and circulation with special reference to changes in the electrical potentials detected by deep electroencephalographic electrodes. The possibility of diagnosis of fatal drowning is examined, based on the results. PMID- 1303438 TI - On the obstruction of arteries and air passage in hanging. PMID- 1303439 TI - Studies on asphyxia: morphological research for the aid of diagnosis of asphyxia using light and electron microscopy and immunohistochemical methods. AB - The lattice-form structure and/or tubular myelin can be found in the debris-like structure which is the pinkish substance in the alveolar space in the Hematoxylin & Eosin stained sections. These findings were obtained by using rats in the air containing oxygen of 5% or mixing and/or contaminating each of methane, carbon dioxide, carbon monoxide and freon gases. The immunohistochemical detection using the monoclonal mouse antibody against human pulmonary surfactant (PS) apoprotein is of highly useful. The positive reaction products observed in the alveolar space indicate the localization of the tubular myelin. The data suggest that the PS appears when the inhaled air contains oxygen in low concentration. The immunohistochemical method using the antibody against human PS apoprotein is worth applying for the diagnosis of oxygen deficiency including the respiratory distress syndrome (RDS) of the new born. We conclude that the appearance of the positive reaction products suggests that, at least, the air did not come in contact with the surface of alveoli, which leads us to the diagnosis of death was from oxygen deficiency, even if we are at the stage when the mode of death is undetermined. PMID- 1303440 TI - Pathological approaches to SIDS. I. Special emphasis on the histopathological differences between SIDS and asphyxia. AB - Histopathological observation was performed to clarify pathological differences of the lung between SIDS and asphyxia. In regard to pulmonary edema, there was no significant difference between SIDS and asphyxia. Occurrences of microemboli in the pulmonary vessels in cases of SIDS showing aspiration of gastric content into the lung, asphyxia and drowning were significantly high, compared with that of SIDS cases without aspiration. PMID- 1303441 TI - Diagnosis of asphyxia on the sudden infant death--prone sleeping position and vomit aspiration. AB - An inevitable conclusion of studies in the Netherlands, Great Britain, the United States and Japan is that sudden infant death syndrome (SIDS) is intimately linked to the prone sleeping position of infants. But this cause of death cannot be explained by the conventional view of SIDS. Although asphyxia would be the most plausible explanation, the cause of death in the majority of SIDS-related deaths in Japan are ruled as SIDS, primarily because administrative autopsies in this country are delayed and the diagnosis is most often made from an external examination only. This lack of autopsy reports also hampers research in this area. Moreover, even where autopsies have been conducted, because of the lack of clear criteria for diagnosis, inconsistent rulings are rendered depending on the judgment of the presiding pathologist. Given these considerations, we undertook to examine the diagnostic criteria for death by asphyxiation among infants sleeping in the prone position, and the problems associated with such a diagnosis. PMID- 1303442 TI - A case of protracted suffocation death. PMID- 1303443 TI - An evaluation of analyzed data of hemoglobin derivatives by CO-Oximeter in medico legal autopsy. AB - We examined blood samples of autopsy cases by a CO-Oximeter and evaluated the data for investigation of death including asphyxia. When sampling methods were examined, oxyhemoglobin (O2-Hb) concentrations increased, and reduced hemoglobin (R-Hb) concentrations decreased, by the contact of the blood with the air, while carboxyhemoglobin (CO-Hb) and methemoglobin (Met-Hb) concentrations appeared to be unchanged. The CO-Hb concentrations in the left heart blood were higher than those of the right. In the cases of death due to cold exposure, O2-Hb concentrations of the left heart blood were prominently higher than those of the right. In the cases of death in house fires and the asphyxiated, O2-Hb concentrations were extremely low (below 10%) in both of the left and right heart blood. PMID- 1303444 TI - Some observations on the use of monoclonal antibodies for the detection of red cell antigens in stain material. PMID- 1303445 TI - Production and application of recombinant monoclonal antibody molecules. PMID- 1303447 TI - Application of commercially available monoclonal blood grouping reagents to detection of antigens in forensic materials. AB - Commercial monoclonal reagents for ABO blood grouping were examined for their characteristics in forensic application. In the absorption-elution tests, the monoclonal reagents showed various reactivities, which were generally weaker than polyclonal ones. False negative reactions were observed in the tests for A antigens in some cases of aged or thin bloodstains and hair samples. Each monoclonal reagent showed a limited reactivity to the stains of animal blood. The monoclonal reagents were comparable to polyclonal ones in the absorption characteristics with bloodstains. They showed various reactivities with salivas. In the immunostaining, each of anti-A and anti-B reagent showed a similar staining property against the group antigens of the red cells, vascular endothelia, and various epithelia including the mucous cells of salivary glands. PMID- 1303446 TI - Efficient methods for production of monoclonal antibodies for forensic applications. AB - To simplify the labor-intensive process of making hybridomas, we fused popliteal lymph node cells, used an autoclavable serum-free culture medium throughout, and cloned hybridomas with human blood cell feeders. To make the best possible use of the serum-free medium, we adapted mouse myeloma cells to it. Using as little as 0.2 ml of human blood per culture plate, we successfully cloned hybridomas and established a hybrid cell line producing anti-peroxidase antibody. Our protocol affords a considerable saving on time, labor, and cost, and hopefully will encourage the forensic scientist to undertake the production of monoclonal antibodies. PMID- 1303448 TI - Comparison of specific reactivity of monoclonal and polyclonal ABH reactive antibodies. PMID- 1303449 TI - Blood grouping of minute samples using monoclonal anti-A,B antibody. AB - The availability of a monoclonal anti-A,B antibody (AB-E6E2) for blood grouping of blood and saliva stains was investigated. The antibody, which was reacted with A, B and AB antigens but not with O antigen, was produced from BALB/c mouse-mouse hybridoma raised to group AB red blood cells. AB-E6E2 had heat-elutability enough to detect ABO antigens in blood and saliva stains by absorption-elution test, whereas it had extremely weak double combining potency in mixed agglutination test. Application of elution-ELISA method will enable the detection of smaller amount of ABH antigens. The antibody, therefore, would be useful to segregate group O minute samples from the other blood group ones. PMID- 1303450 TI - A novel method for blood group typing with the aid of monoclonal antibody immobilized dyed microspheres. AB - A novel and simple method for blood group typing has been developed. The procedure involves the use of type-specific monoclonal antibodies covalently linked to dyed microspheres of polyglycidyl methacrylate. The presence of ABH and Lewis blood group antigens in saliva and plasma could be determined easily and specifically with respective monoclonal antibodies bound to dyed microspheres. The present method could also be applicable for the determination of the presence of invisible antigens for the forensic and diagnostic purpose with visible agglutination reaction. PMID- 1303451 TI - Monoclonal antibodies against haptens. AB - Four kinds of monoclonal antibodies (moAbs) specific to paraquat, diquat, methamphetamine (MA) and melatonin (MT) were produced. 1-Methyl,1'-hexanoic acid 4,4'-bi-pyridinium, 4-amino-D,L-phenylalanine-diazo-coupled diquat, p-amino methamphetamine as haptens were synthesized and coupled to bovine serum albumin (BSA) directly or to BSA via glutaraldehyde, and an antigen of MT was prepared by binding MT to BSA with the Mannich reaction. These immunogens of BSA conjugates were immunized i.p. to BALB/C mice. Usable moAbs were established 4 to 6 months after the first immunization. Amounts of paraquat, diquat, MA and MT causing a 50% of inhibition by enzyme-linked immunosorbent assay or radioimmunoassay with one of the most specific moAbs from each hapten were 1.1 ng, 0.67 nmol, 10.0 ng and 1.4 ng, respectively. PMID- 1303452 TI - Genetic polymorphism of complement component C6, C7 and C8(1) in Chinese Han population in northeast China. AB - Distributions of complement phenotypes, C6, C7, and C8(1) were studied using thin agarose gel isoelectric focusing (AGIEF) or ultra-thin polyacrylamide gel isoelectric focusing (PAGIEF) and subsequent immunoblotting techniques in 203 Chinese Han population in Liaoning Province of northeast China. The gene frequencies were as follows: C6*A 0.4704, C6*B 0.5049, C6*B2 0.0148, C6*B3 0.0049, and C6*M 0.0049; C7*1 0.8251, C7*2 0.1108, C7*3 0.0320, and C7*4 0.0320; C8(1)*A 0.5567 and C8(1)B 0.4433, respectively. All the observed numbers of the phenotypes were in agreement with the expected numbers under the Hardy-Weinberg equilibrium. The gene frequencies among Chinese subpopulations and other various populations were compared. PMID- 1303453 TI - [DNA typing and analysis of the D1S8 (MS 32) allele in the Japanese population by the minisatellite variant repeat (MVR) mapping by polymerase chain reaction (PCR) assay]. AB - Minisatellite variant repeat (MVR) mapping using the polymerase chain reaction (PCR) of the D1S8 (MS32) locus from total genomic DNA and size separated alleles in the Japanese population was performed. DNA was extracted from blood in healthy non-related Japanese individuals. The digital data obtained were computer analysed, and from this single assay all unrelated individuals tested could be unambiguously distinguished. The average difference in diploid codes between unrelated individuals was 36 exclusions over the first 60 repeat unit positions. The mean proportions of a-, t-, and 0-type repeat units were 73.5%, 24.5% and 2.1%, respectively. MVR-PCR gives digital profiles which show extreme levels of individual variation and should prove very useful for personal identification. The advantages and further applications of MVR-PCR are also discussed. PMID- 1303454 TI - [Sensitive identification of human blood and simultaneous determination of ABO blood group from a minute bloodstain by an ELISA-ABC method]. AB - Sensitive identification of human blood and the determination of ABO blood group from a minute bloodstain were simultaneously carried out by a direct ELISA-ABC method. A cotton thread (1 cm in length) stained with 1 microliter of human or animal blood was stored for 2-4 weeks at room temperature. Hemoglobin (Hb) of the bloodstained thread was gently extracted with 100 microliters of PBS at room temperature, and the thread was washed with PBS to dehemoglobinize. And ABH blood group antigens were extracted from the same dehemoglobinized thread with 100 microliters of 5% ammonia solution at 56 degrees C. The extracts of PBS and ammonia were two-fold serially diluted with 0.1 M sodium carbonate buffer, coated to the wells of a flat bottomed microplate. The PBS extract was tested with a biotinylated antibody against human HbA0 for identification of human blood. Human blood was clearly distinguishable from bloods of other species including Japanese monkey. The minimum detection limit of human blood of the PBS extract of the bloodstained thread was 1:40,960 (3.4 ng Hb), and the limit was found to be approximately 200 times higher than that obtained by a leucomalachite green test or by a precipitation ring test using anti-human HbA serum. The ammonia extract was tested with biotinylated anti-A, anti-B and anti-H antibodies for ABO blood grouping. ABH antigens of the ammonia extract of the bloodstained thread were clearly detected. The minimum determination limits of blood group A, B, AB and O of the ammonia extracts were 1:160, 1:160, 1:80 and 1:160, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303456 TI - Otoacoustic emissions (OAE) in paediatric hearing screening--the Singapore experience. AB - Early identification and rehabilitation of hearing impairment is important for development of language in affected children. Behavioural audiological tests in children are unreliable. Brainstem auditory evoked response (BAER) although a reliable objective test, is difficult to perform. Otoacoustic emissions (OAE) is now thought to be a more practicable screening modality. A study to compare the use of OAE and BAER in the paediatric population was thus undertaken. 100 children underwent OAE and BAER screening in SGH from August 1991 to February 1992. OAE was equally effective when compared with the BAER in testing for passed or failed subjects (p < 0.05, X2 = 4.9). The sensitivity and specificity of OAE with respect to BAER was 95% and 93% respectively. Mean test time was 3.1 minutes for OAE and 28.6 minutes for BAER. Success rate for OAE was 100%. We therefore conclude that OAE is a feasible alternative to the BAER as a hearing screening modality. PMID- 1303455 TI - [Analysis of pedestrian injuries in traffic accidents: impact point, injury portion, and injury severity]. AB - We conducted in-depth case studies of traffic accidents involving 118 pedestrians, who were struck by the fronts of bonnet-type cars. The data were reviewed in order to correlate injury severity with pedestrian age, and area of body contact, contact surface of vehicle or the local environment, and impact speed. It was found that head injuries caused by impacts against the top surface of car bonnets and leg injuries caused by front bumpers both showed high incidence rates. Both head and leg injuries caused by striking the vehicle were more severe than those caused by striking the road surface. In cases of impact between the head and the solid portion of the vehicle, such as the A-pillar, or in cases of secondary impact between the head and underhood solid structures such as shock tower, injuries tended to be more severe. The location of head impact varied according to the stature of the pedestrians. PMID- 1303457 TI - Recurrent chest pain in childhood: a diagnostic challenge. PMID- 1303458 TI - Peripheral artery cannulation in newborns. AB - This report outlines our experience (retrospectively over a 3-year period) with peripheral artery cannulation for blood gas monitoring in 170 newborn infants. The technique for radial artery cannulation is described in detail. Recorded sites of cannulation were radial (138), posterior tibial (34), dorsalis pedis (2) and temporal (1). Only minor complications occurred which were transient ischaemia (19 cases), accidental blood loss (4 cases) and superficial abscesses (2 cases). Three other cases were suspected to have systemic infection but these were not proven. Cannulae had to be removed in 52% of cases because no blood could be withdrawn for sampling. It is concluded that peripheral artery cannulation in the newborn is a safer and more convenient procedure than umbilical artery catheterisation. PMID- 1303459 TI - PaO2, SaO2 and what constitutes adequate oxygenation in the premature newborn. AB - 3 neonates admitted into our intensive care unit had their arterial blood gases analyzed. A total of 64, 67 and 73 arterial blood samples were analyzed for the 3 neonates respectively. The relationship between PaO2 and the corresponding SaO2 were plotted in an oxygen hemoglobin dissociation curve. PaO2 of 50mmHg corresponded to SaO2 of 80%, 84% and 92% for the 3 babies respectively, reflecting the fact that SaO2 can differ considerably. PaO2 of 50mmHg or SaO2 of 87% by themselves are inadequate as indicators of lower limit of arterial oxygenation. Indeed a consideration of other factors such as oxygen consumption, cardiac output, hemoglobin concentration are integral to this issue. PaO2 of 70mmHg corresponded to SaO2 of 92%, 93% and 97% respectively. However, at the upper limit of arterial oxygenation, the oxygen hemoglobin dissociation curve flattens out and PaO2 is a more sensitive indicator of the upper limit of arterial oxygenation as compared to SaO2. PMID- 1303460 TI - Mycoplasma infection in children. AB - One hundred and eleven children with Mycoplasma pneumonia infection were studied. Their mean age was 6.2 +/- 3.1 years. The two commonest symptoms were cough (98%) and fever (95%). Only 23% of children had cough of greater than one week's duration. Ninety one per cent had positive chest signs. Radiological abnormalities were seen in 95% of chest x-ray. Complications included dermatological (10%), pleural effusion (5%), neurological disorder (3%), septicaemia (1%), bronchiectasis (1%). Two children with Down's Syndrome died. A rare case of Mycoplasma bronchitis with Reye's Syndrome was observed. PMID- 1303461 TI - Complications of severe lower respiratory tract infections in Singapore children. AB - Over one year period, 240 children with severe lower respiratory infection was admitted to a general paediatric department. The mortality was 1.6%. Apart from pleural effusions and skin exanthems, several major complications were noted. These were septicaemia (1), apnoea (2), encephalopathy (3), meningitis (1), Stevens Johnson Syndrome (1), bronchiectasis (1) and lung abscess (1). PMID- 1303462 TI - Use of intravenous midazolam for sedation in children undergoing ward procedures. AB - Midazolam is a water-soluble benzodiazepine with low toxicity. It has anxiolytic and sedative effects. This study assessed the efficacy and tolerance of this drug for sedation in various ward procedures. Pethidine was added to bone marrow aspirations for analgesia. 57 children with the mean age of 48 months and mean weight of 15.7 kilograms were studied. The dose of midazolam used to sedate adequately 86% of the children was 0.73mg/kg, the average onset of sedation was 4.3 minutes and mean duration was about 88 minutes. 47.5% were completely sedated, whereas 38.5% were only partially sedated. In 14%, sedation was not achieved at all. There was a statistically significant drop in blood pressure after sedation but this was not associated with any clinical effects. Hypoventilation was not detected in this study. PMID- 1303463 TI - Discharges of children from hospital against medical advice. AB - A retrospective study on discharges of children from hospital against medical advice or at own risk (AOR) discharges was conducted at our department from March 1981 to February 1990. There were altogether 890 patients giving an average incidence of 2%/year. The racial composition comprised 62.5% Chinese, 28.5% Malay, 7.3% Indian and 1.7% others. The common reasons for AOR discharge includes: (a) Inconvenience of having the child hospitalised (18.4%). (b) Preference of being treated by the general practitioner (15%). (c) Parents think child is well (14%). (d) Preference of being treated by private specialist or other hospital (11.9%) etc. Neonate comprised 16.9%, infants (except neonates) 44%, children > 1-5 yrs 28.6%, > 5-10 yrs 7.7% and > 10 yr 1.9%. The common diagnoses of these children include gastroenteritis (13.9%), febrile fit (13%), upper respiratory tract infection (11.7%), neonatal jaundice (5.7%). In conclusion AOR discharges of children from hospital is not uncommon and more could be done to reduce the incidence. PMID- 1303464 TI - Cutaneous neonatal lupus erythematosus in Chinese neonates. AB - Neonatal lupus erythematosus (NLE) is a well established subset of Lupus erythematous (LE). Three chinese female neonates presented to our Skin Centre, from May 1990 to May 1991 with NLE. All had skin lesions without congenital heart block and systemic problems. Two had photosensitive annular erythematous lesions on scalp, urticarial lesions on body, and one with facial atrophy, with aplasia cutis congenita. The biopsies were non specific while one had C3 in vessel walls. The major serogical marker was anti La antibody/SSB in two babies and anti Ro antibody/SSA in one. Two mothers were known cases of LE and one, was undiagnosed. Two infants were treated with short term low dose prednisolone. The infants will require long term follow up with paediatricians, in view of the fact that they can develop SLE later. The diagnosis of NLE is emphasised in infants with facial lesions to avoid delay in diagnosis, and full work up in both infants and mother is necessary. PMID- 1303465 TI - Air embolism in the newborn. PMID- 1303466 TI - Obesity-cerebral-ocular syndrome--a case report. AB - The obesity-Cerebral-Ocular Syndrome is an uncommon disorder which closely resembles the Laurence-Moon-Biedl-Syndrome. It is also one of several disorders in which obesity, mental retardation and ocular abnormalities are associated. The article presents a case study followed up over 18 years and emphasises the importance of ophthalmic review in preserving visual function. PMID- 1303467 TI - Growth and pubertal assessment after treatment in acute leukemia. AB - To evaluate the effect of leukaemia and its treatment on growth and puberty, we studied retrospectively the serial heights and pubertal development of 37 children with acute leukaemia. The age of diagnosis ranged from 10 months to 13 years, with a duration of follow-up varying from 2 years to 14 years. The SDS (Z score) which reflects the deviation of height measurements from the population mean was used to assess height change at yearly intervals. Pubertal assessment was also made using the Tanner standards. 25 (69%) children showed a falling trend in mean Z scores over a 5 year follow-up period. The difference between the mean Z scores at 0 and 5 years was statistically significant (p < 0.035). However, there was no significant correlation between age of onset of disease and duration of survival with the deviation in the Z score. 11 children did not demonstrate a fall in the Z scores. There were, however, no defined factors such as age of onset, duration of follow-up, and sex distribution which could predict growth failure. Pubertal assessment showed normal development in all children with the pubertal age group (n = 11), except for 3 boys, two of whom had received testicular irradiation. PMID- 1303468 TI - Detection and molecular analysis of alpha and beta thalassaemia genes--recent developments in screening protocols. AB - Molecular and non-molecular techniques have been utilized for the detection and characterisation of alpha- and beta-thalassaemia genes. Non-molecular techniques example, haematological indices and haemoglobin electrophoresis allow samples to be screened rapidly without the use of radionuclides but these techniques are unable to detect mutations at the gene level. Molecular analysis of alpha- and beta-globin genes either by Southern Blotting and radionuclides or DNA amplification using the polymerase chain reaction (PCR) allows detection of specific mutations and have enabled prenatal diagnosis of the thalassaemias. PMID- 1303470 TI - Ingested foreign body in young children. AB - Locally, ingested foreign body is a problem commonly seen in the adult patients. Paediatric patients constituted about 6.5% of all cases of ingested foreign body. In adults and older children who are able to communicate, the management is usually straight forward. However, the diagnosis of ingested foreign body in a prelingual child may pose a problem as the child is unable to talk. A high index of suspicion is needed in the diagnosis of ingested foreign body. This article presents a case of undiagnosed ingested foreign body causing pharyngeal perforation with retropharyngeal abscess in a two year-old boy. The management of ingested foreign body in young children is discussed. PMID- 1303469 TI - Routine immunisation against chickenpox. Is it time? AB - Natural varicella in healthy children is normally not a severe illness. Nevertheless, the need to be away from school such as during an important examination, or from work, may be inopportune. It is therefore attractive to be able to prevent chickenpox. Such a proposition became a reality in 1974 with the development of a live attenuated varicella vaccine (the Oka strain). This has since been used in leukaemic children and children with other malignancies, and found to be safe and effective. Some of these children were immunised without complete suspension of anticancer therapy. The vaccine has also been used on healthy children and adults, mainly in Japan and North America. The results too indicated the vaccine to be safe and immunogenic, with minimal side effects. It has been shown to confer protection even if given within 3 days of exposure. The occurrence of zoster appears to be no higher than in natural infection. The vaccine has so far been shown to be protective up to 10 years post-immunisation. It appears safe enough to offer the vaccine routinely to those who are at risk of infection. One dose of vaccine given subcutaneously is usually sufficient for healthy children, but two doses are needed for immunocompromised children and adults. PMID- 1303471 TI - Epidemiology of dengue and dengue haemorrhagic fever in Malaysia. III. A comparative study of clinical features seen in virologically confirmed cases for periods between 1963-1987--a review. AB - Dengue fever, Dengue hemorrhagic fever and Dengue shock syndrome within the dengue complex is a sinister disease of great public health importance and continues to ravage children, young adults and the aged in Malaysia. The history of the disease is traced for over the years and the changing pattern of clinical presentation are noted. Various hospital based studies have been compared and the pathognomonic features of the disease in Malaysia are highlighted. PMID- 1303472 TI - Physiological consequences of status epilepticus. PMID- 1303473 TI - Mechanisms of brain damage in status epilepticus. PMID- 1303474 TI - Recent advances in childhood acute lymphoblastic leukemia. PMID- 1303475 TI - Current status of medical biotechnology in Malaysia. PMID- 1303476 TI - A supersensitive in-house enzyme-linked immunosorbent assay (ELISA) for measurement of thyroid-stimulating hormone (TSH) and its clinical applications. AB - A supersensitive ELISA was developed for measurement of thyroid-stimulating hormone (TSH) concentrations in serum using in-house rabbit polyclonal antisera and a commercial monoclonal antibody. The assay was optimised and validated by recovery, linearity and cross-reactivity experiments and further compared to other available assays and EQAS samples. Good precision was obtained with a working assay range of 0.2 to 100 mIU/L with < 10% coefficient of variation (CV) for both intra and interassay. The assay is highly sensitive and specific with a minimum detectable limit of 0.07 mIU/L and negligible cross-reactivities against LH, FSH, HCG and other pituitary peptides. Good correlations were obtained when compared to Abbott hTSH EIA (r = 0.993; p < 0.001; n = 85) and NETRIA IRMA (r + 0.995; p < 0.001; n = 76). The normal reference range established was 0.4 to 4.0 mIU/L (n = 76). TSH levels in serum of thyrotoxic patients (n = 83) were significantly lower (0.07 to 0.20 mIU/L, p < 0.0001) and completely distinct from normal values thereby obviating the requirement of a TRH-stimulation test. Stability studies showed that coated wells can be stored at 4 degrees C for at least 2 months. This highly sensitive in-house hTSH ELISA which is cheap, stable and readily available is useful for diagnosis and management of patients with various thyroid disorders. PMID- 1303477 TI - Spirometry and flow-volume in Malay adults. AB - Respiratory function testing was done using a portable electronic spirometer in 223 normal Malay subjects between the ages of 15 to 75 years. Tests of FEV1, FVC, PEFR, and MMF were recorded using standard forced expiratory maneuvers. Malay adults have lower respiratory function values compared to Caucasians and other Asians. PMID- 1303478 TI - Treatment of bleeding gastroesophageal varices: a report of forty-four cases. AB - Bleeding gastroesophageal varices is associated with a high morbidity and mortality. Forty-four cases of bleeding gastroesophageal varices were treated at the Department of Surgery, Universiti Kebangsaan Malaysia, General Hospital, Kuala Lumpur over four and a half years. Thirty-two of them had liver cirrhosis. Hepatitis B infection was noted in 13 and alcoholic abuse was present in 14 patients. Five patients had associated hepatoma. Thirty-four percent had gastric fundal varices and a third of these bled from them. A total of 179 endoscopic injection sclerotherapy sessions were performed averaging 4 per person. Rebleeding rate was 4% and mortality was high (50%) in these cases. It was concluded that injection sclerotherapy is a safe and effective means of controlling bleeding oesophageal varices. Operative surgery was employed in those who rebled after injection and would be considered in those in Child's A. PMID- 1303479 TI - The role of prophylactic antibiotics in caesarean section--a randomised trial. AB - A prospective randomised controlled study was conducted over a 6 month period on the value of administering prophylactic antibiotics in patients undergoing emergency caesarean section at the Ipoh General Hospital. A total of 222 patients were randomised to receive 24 hours of ampicillin (500 mg per dose), cefoperazone (1 gm per dose) or no antibiotics. In all parameters of patient morbidity, the group receiving cefoperazone showed significantly better results as compared to the group not receiving antibiotics. The ampicillin group also had favourable results but generally not achieving statistical significance. Prophylactic antibiotics appear to be beneficial and consideration should be given to make it a routine in all emergency caesarean sections. PMID- 1303480 TI - Propofol and methohexitone for elective caesarean--a comparative study. AB - Two identical groups of females underwent caesarean operations. One group was induced with propofol 2.04 (SD 0.023) mg per kilogram and the other group induced with methohexitone 1.05 (SD 0.15) mg per kilogram body weight. Maintenance of anaesthesia was identical in both groups. Post-intubation blood pressure in the methohexitone group was significantly raised whereas with propofol the changes were not significant. There were no significant differences in the Apgar scores, uterine contractility and umbilical venous or arterial blood gases. There was a significant difference in the analgesic requirement in the first hour of the post operative period; in the propofol group, patients needed less analgesia compared to the methohexitone group. There was no maternal awareness in both groups. PMID- 1303481 TI - Routine coagulation tests in cases of missed abortion--is it really necessary? AB - Many gynaecological units have a policy of performing routine coagulation tests in cases of missed abortion. For many years now, it has been accepted practice in our unit to perform routinely a platelet count, bleeding time (BT), clotting time (CT) and plasma fibrinogen (P. fib) level prior to evacuation in cases of missed abortion. We are not sure how or why these 4 tests came to be chosen as a coagulation 'screen'. As they are not totally adequate in detecting disseminated intravascular coagulation (DIC), we wondered if these tests added to the management in any way. PMID- 1303482 TI - Once daily felodipine monotherapy in mild to moderate hypertension. AB - In a single-blind study conducted at our centres, 78 hypertensive patients were enrolled with 58 completing the study according to the protocol. Mean supine and standing blood pressures were significantly reduced after treatment with felodipine, reductions being 27/21 mmHg (p < 0.0001) and 25/19 mmHg (p < 0.0001) respectively. Of 46 patients given felodipine 5 mg, 44 (95.7%) achieved target blood pressure defined as a diastolic blood pressure of < 90 mmHg, while all 12 patients on felodipine 10 mg did so. The 2 patients who did not achieve target pressure at the final visit did so on previous visits. There were no differences in pre and post-treatment laboratory variables. Treatment was discontinued in 6 patients because of headaches. No adverse events of clinical significance were reported in the 58 patients who completed the study. In conclusion, we found felodipine given once daily to be effective in the treatment of mild to moderate hypertension. PMID- 1303483 TI - Carcinoma of the larynx in Malaysia. AB - A retrospective study of cases with carcinoma of the larynx seen in the Universiti Kebangsaan Malaysia (UKM) and General Hospital Kuala Lumpur (GHKL) between 1981 to 1988 was performed. The aim was to document the distribution and the pattern of behaviour of this tumour amongst our patients. There were 137 cases, the majority of whom were Chinese (54%). The peak incidence was in the seventh decade and the male to female ratio was 7.6:1. The most common symptom at presentation was hoarseness (90%). The most common histological type was squamous cell carcinoma (87%) whilst by site, transglottic involvement was commonest (55%). The overall 3 year survival rate was 68%. Supraglottic carcinoma behaved differently in that a significantly large number presented with dysphagia (33.3%) and neck nodes (42%). Compared to tumours of other sites of the larynx, they had the poorest 3 year survival rate of 50%. Amongst the T2 and T3 tumours, the results of surgery appeared better than primary radiotherapy. Considering that 26% of patients presented with stridor, 20% with neck nodes and 55% with multiple site involvement, it can be concluded that our patients present themselves late. PMID- 1303484 TI - A one year community-based study on the incidence of diarrhoea and rotavirus infection in urban and suburban Malaysian children. AB - A 1 year longitudinal study of 156 Malaysian children from urban and suburban areas in the Klang Valley revealed that the incidence rate of diarrhoea was 23.6 per 100 person-year with abnormal faeces reported on 0.26% of the total days of observation. Diarrhoea cases were detected in children from all socioeconomic classes. Rotavirus was isolated from 12% of the diarrheic children and asymptomatic rotavirus infection occurred in 3.2% of the children. All rotaviruses isolated were group A rotaviruses with long electrophoretypic pattern. PMID- 1303485 TI - Chlamydia pneumoniae respiratory infection in a child--a case report. AB - A case of respiratory infection in a child due to Chlamydia pneumoniae is reported. The diagnosis was made by the detection of chlamydial antigen in the tracheal secretion and a significant increase in C. pneumoniae antibody titre. The infection responded well to erythromycin therapy. PMID- 1303486 TI - A case of empyema thoracis caused by actinomycosis. AB - A female patient who presented with left empyema thoracis caused by Actinomyces odontolyticus is reported. She responded to treatment with penicillin and metronidazole but after 3 weeks developed leucopenia complicated by gram-negative septicaemia. Leucopenia improved rapidly on withdrawal of metronidazole. Treatment was continued with a prolonged course of penicillin and she made an uneventful recovery. PMID- 1303487 TI - The use of interventional radiology in ruptured solitary kidneys. AB - This case report illustrates how a life-threatening renal bleeding which has failed to be controlled by open surgery can be elegantly managed by a minimally invasive technique of interventional radiology. It also allows maximal conservation of renal tissue so that the patient can avoid chronic dialysis or renal transplantation. PMID- 1303488 TI - The surgical treatment of multiple small bowel strictures in Crohn's disease by combined resection and stricturoplasty. AB - Crohn's disease is extremely rare among Asians. Resection of strictures causing obstruction has traditionally been the accepted choice in surgical therapy. This may lead to problems such as iatrogenic short bowel syndrome and its sequelae. Stricturoplasty is an acceptable and safe alternative. We report a case where combined stricturoplasty and resection was performed safely and advocate its use. PMID- 1303490 TI - Imported cases of chloramphenicol resistant Salmonella typhi. PMID- 1303489 TI - Schistosoma haematobium infection in Malaysia--a case report. AB - An imported case of Schistosoma haematobium infection presenting with haematuria and proteinuria is described. This would constitute a first case of urinary schistosomiasis in Malaysia. The patient failed to respond to multiple antibiotic treatment and was successfully treated with praziquantel. PMID- 1303491 TI - [Genetics and cancers]. AB - Multiple genome alterations can be seen within a tumor and continue to accumulate throughout development of the growth. Chromosome deletions occurring in tumors are generating much interest. To date, the best known model is retinoblastoma whose study gave rise to the concepts of anti-oncogene or tumor suppressor gene. Studies of genetic anomalies in colorectal tumors have led to an elegant model of colonic carcinogenesis in which multiple steps, each with its corresponding genetic anomaly, successively accumulate, with deletion of the p53 gene occurring as a late event. Successive anomalies of the p53 gene (mutations, deletions) occur during passage from a low-grade astrocytoma to a higher-grade astrocytoma. Studies of familial forms of breast cancer and of breast and ovarian cancer have also provided insight into the biology of these tumors, with the identification of a predisposing chromosomal area whose location is 17 q-12-21. These approaches open up possibilities for screening techniques and use of preventive treatments in highly selected patients. However they raise many ethical problems. There is a need for developing a charter for these family studies in the near future. PMID- 1303492 TI - [Epidemiology and treatment of stomach cancer: news in 1992]. AB - Four studies presented at the 1992 ASCO and AACR meetings are analysed. Wanebo compared treatment of gastric cancer in the USA and in Japan. Retrospective analysis of 18,365 patients showed an important delay in diagnosis and surgical treatment without radical lymph node dissection (less than 10%) in the North American patients. In 1982, the overall 5-year survival in the USA was 17.5%, not different from that of thirty years ago. MacDonald undertook a prospective randomised study of adjuvant FAM chemotherapy in 221 patients operated on for gastric cancer. With a median follow-up of 7 years, the median overall and disease free survival were respectively 36 and 29 months in the FAM group and 28 and 22 months in the control group. These differences were not significant and the authors concluded that FAM is not an effective adjuvant chemotherapy in resected gastric cancer. Ajani studied the efficacy of pre and post-operative EAP (etoposide, adriamycin, platine) chemotherapy in fourty-eight patients with potentially resectable gastric carcinoma. The overall clinical response rate was 31%, fourty-one patients were operated on and thirty-seven had a curative resection (70%). There was one chemotherapy related death. These data indicate that pre and post-operative EAP chemotherapy is feasible and effective in patients with potentially resectable gastric carcinoma. Correa made a lecture on human gastric carcinogenesis. The "intestinal" type of gastric cancer appears to be the end result of a long series of cellular changes called "multifocal chronic atrophic gastritis". Alterations in the function of the gland neck cells appear to be responsible for the preneoplasic changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303493 TI - [Treatment of disseminated malignant melanoma. Results are promising, but toxicity is high]. AB - After the promising results achieved with immunotherapy in disseminated malignant melanoma, a disease reported to show little response to chemotherapy, use of combination chemotherapy regimens with interferon or interleukin and interferon has been shown to provide higher response rates and responses of longer duration. A few phase I-II trials on monoclonal antibodies have also been reported. However, toxicity is substantial with these complex combination regimens. PMID- 1303494 TI - [Issue devoted to Professor Georgy Kryzhanovsky, full member of the Russian Academy of Medical Science]. PMID- 1303495 TI - [Pathophysiologic mechanisms of psychopathologic phenomena and psychopharmacotherapy]. AB - The paper is concerned with the questions of genesis of psychopathological symptomatics in terms of the theory of Academician G. N. Kryzhanovsky of determinant structures and generator activity. The complexity of experimental modelling of severe psychopathological disorders is indicated since not all psychopathological phenomena possess objective characteristics. It should be keep in mind that the psychopathological method itself is a subjective one. The stability of clinical manifestations of psychoses, e.g. schizophrenia, and reactions to the psychopharmacotherapy in an individual over a long period of time suggests the involvement in pathological process of determinant structures. Variety of clinical manifestations of schizophrenia is predetermined by unequal involvement of the brain hemispheres. In connection with this one may think about the determinant structures and generator mechanisms predominating in either hemisphere. Quantitative EEG investigation in schizophrenia patients with hallucinatory-paranoid and schizoaffective symptomatics showed that in the former group after a week long therapy using stelazine the activation of the left hemisphere prevailed, and in the latter group--of the right one. Stelazine predominantly blocks the hemisphere in which generator processes are weaker (the right one in the case of hallucinatory-paranoid syndrome, and the left hemisphere with the schizoaffective one). This accounts for a great probability of development of postpsychotic depression in the patients with the schizoaffective syndrome after administration of neuroleptic therapy. Phenomenologically similar psychopathological symptomatics, in particular a depressive one, can occur as a result of the activities of various determinant structures. Anxiety, unlike other psychopathological phenomena, is responsive to practically all types of psychotropic compounds with different mechanisms of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303496 TI - [Systemic mechanisms of nervous disorders]. AB - Apart from the lesion and destruction of nervous structures and nervous links there is a different, so far little known, aspect of pathogenesis of nervous disorders, i.e. appearance of new pathological integrations in the nervous system. Formation and activity of these integrations is realized by endogenous, intrinsic to the damaged nervous system itself mechanisms. Pathologic integration occurring at the level of systemic relations is a pathologic system. The main biological sign of a pathologic system, due to which it differs from a physiologic system, is a dysadaptive or directly pathogenic significance of its activity for the organism. The pathologic system may be originate as a result of hyperactivation and loss of control over the physiologic system or due to the formation of a new, pathodynamic organization in the central nervous system. The neuropathological syndrome is clinical expression of the corresponding pathologic system activity. Every syndrome has its pathologic system and the specificity of the syndrome depends on what structures of the central nervous system are part of the pathologic system. Simple, linear pathologic systems underlie the monomorphic syndromes and symptoms, and complex ones underlie the polymorphic syndromes. Due to plasticity the positive connections between the parts of the pathologic system are consolidated therefore with course of time the resistance of the pathologic system to the endogenous sanogenetic mechanisms and to therapy increases. Stabilization of pathologic system underlies the chronization of nervous disorders. The concept of the pathologic system as a basic pathophysiological mechanism of nervous disorders is a new approach to understanding pathogenesis, elaboration of models and development of new principles and method of treatment of nervous disorders. PMID- 1303497 TI - Second messengers derived from excitable membranes are involved in ischemic and seizure-related brain damage. AB - The intracellular accumulation of PAF following cell stimulation suggests an intracellular signal transduction pathway. High affinity binding sites for PAF in microsomal membranes and displacement of PAF from these sites by structurally distinct PAF antagonists suggests the existence of an intracellular receptor. Suppression of primary genomic responses by a PAF antagonist selective for the intracellular Ca2+ and arachidonic acid metabolites, is linking the intracellular generation of PAF to immediate-early transcription. Several of the metabolites that transiently accumulate after injury may elicit beneficial effects on regenerative processes. The membrane metabolite PAF, which accumulates after seizure and ischemia, may initiate reparative processes by promoting transcriptional activation of immediate-early transcription factors. The long term effects of these immediate-early gene transcription factors may provide a synthetic mechanism to replenish and rebuild cells following traumatic events. PMID- 1303498 TI - Sequelae of biochemical events following photochemical injury of rat sensory motor cortex: mechanism of ganglioside protection. AB - In culture the protracted and abusive stimulation of glutamate (GLU) receptors results in neuronal death through a mechanism involving the persistent translocation of PKC and the destabilization of (Ca2+)i homeostasis [(Ca2+)i HD]. In contrast, intermittent GLU receptor use elicits a coordinated expression of immediate early genes (IEG) acting as nuclear third messenger. Brain ischemia also is known to result in the paroxysmal abusive stimulation of glutamate receptors. The glutamate receptive elements in turn degenerate largely as a function of their inability to control homeostatic Ca2+ due to the irreversible translocation of PKC. In the present study we employed an in vivo model of focal brain ischemia using the photosensitive dye, Rose bengal. With this model we sought to determine the neuroprotective actions of MK-801, a noncompetitive blocker of GLU at the NMDA-sensitive receptor and of the semisynthetic gangliosides LIGA 4 and LIGA 20 which in vitro have been demonstrated to block PKC translocation. Moreover, we sought to establish whether the persistent stimulation of ionotropic glutamate receptors would led to a change in ionotropic glutamate expression in the focal and perifocal area. Importantly, the perifocal area (i. e., the region surrounding the area of primary insult) is a region in which profound cellular reorganization occurs including neuronal death and glial proliferation and is a key region to target various neuroprotective drugs aimed at ameliorating the neurodegeneration following stroke. Receptor abuse dependent antagonists (RADA) drugs such as gangliosides selectively curtail the amplification steps that specifically differentiate signal transduction following physiological receptor use from that following pathological receptor abuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303499 TI - Potential physiological and pathophysiological roles of nitric oxide in the brain. AB - Nitric oxide (NO) is a free radical molecule which has been described to play a role as a messenger molecule in at least three systems: white blood cells, blood vessels and most recently in the nervous system. In the brain, NO is produced enzymatically in postsynaptic structures in response to activation of excitatory amino acid receptors. A major action of NO is to activate soluble guanylate cyclase and to raise cGMP level in target cells. The role of NO as a messenger in long-term potentiation and in long-term depression has been established and recent studies have directly implicated NO in neuronal damage associated with vascular strokes. Concerning the role of NO in the excitatory amino acid neurotoxicity, more studies will be necessary to elucidate the implication of NO mediating neuronal damage. Whatever the exact function of NO, it is sure that this substance play an important role in the brain and that pharmacological manipulations of NO pathway will constitute a novel approach for therapeutical applications in the future. PMID- 1303500 TI - [Possible molecular mechanisms of brain dysfunction in phenylketonuria]. AB - Recent experimental data are summarized about changes in the functioning of calcium ion channels in clonal cellular lines (pheochromocytoma PC12) and hippocampal neurons of newborn rats on the background of altered intracellular level of aromatic amino acid L-tyrosine or its precursors L-phenylalanine. Elevation of the level of L-phenylalanine persistently down-regulated the high threshold voltage-operated calcium channels in both types of cells without affecting the low-threshold ones in hippocampal neurons. This depression could be to some extent reversed by elevation of the level of L-tyrosine. Thus both amino acids seem to exert a long-lasting antagonistic modulatory effect on the corresponding channels, mediated probably through changes in tyrosylation of some cytoskeletal proteins. The participation of these molecular mechanisms in brain dysfunction during congenital disease phenylketonuria is suggested. PMID- 1303502 TI - [Dynamics of the functional state of the brain in acute focal ischemia]. AB - Complex clinical-neurophysiological investigation of 200 patients with cerebral acute focal ischemia was carried out. It included polymodal monitoring of brain functional activity: monitoring of electroencephalography (EEG), compressed spectral array and toposelective mapping of somatosensory evoked potentials, acoustic short-latency evoked potentials, transcranial cortical electric stimulation, electromyo- and electroneuromyography. The development of acute focal cerebral ischemia was shown to be independent of its location, kind and prognosis, accompanied by functional reorganization of whole brain: its supersegmented specialized motor and sensory functional systems, nonspecific formations of segmental peripheral system. These changes in cerebral functional activity can be found already during first hours of ischemia and they remain generalized during 3-5 days. PMID- 1303501 TI - Acute and chronic epileptogenesis. PMID- 1303503 TI - Immediate-early genes in the nervous system-are they involved in mechanisms of chronic pain? AB - Evidence suggests that long-term changes in the nervous system may represent a cause of chronic pain. Recent processes became accessible at the cellular level of the nervous system by analyzing immediate-early genes (IEG). The nuclear proteins encoded by these genes function as transcription factors, i.e. they control the expression of other genes. Many conditions of physiological and pathological stimulation can activate IEGs in the nervous system, and these findings have led to the concept of "stimulation-transcription-coupling". Noxious stimuli such as electrical C-fibre stimulation, noxious skin heating or subcutaneous formalin injection result in the transsynaptic induction of the IEG encoded proteins c-Fos, C-Jun and Krox-24, in the dorsal horn of the spinal cord. Non-noxious stimuli usually fail to induce the expression of IEGs. Nerve lesions result in a selective expression of C-Jun protein in the axotomized nerve cells, both in the peripheral and central nervous systems. Expression of IEGs after noxious stimuli and nerve lesions last for days or weeks, indicating profound alterations in the biochemistry and function of nerve cells. These changes could be involved in central nervous mechanisms of chronic pain. PMID- 1303504 TI - G. N. Kryzhanovskii (the 70th anniversary). PMID- 1303505 TI - Phantom limb pain. AB - A phantom limb is universally experienced after a limb has been amputated or its sensory roots have been destroyed. A complete break of the spinal cord also often leads to a phantom body below the level of the break. Furthermore, phantom breasts, genitals and other body areas occur in a substantial number of people after surgical removal or denervation of the body part. The most astonishing feature of a phantom limb (or other body area) is its incredible "reality" to the person. An examination of phantom limb phenomena has led to a new theory. It is proposed that we are born with a widespread neural network--the "neuromatrix"- for the body-self, which is subsequently modified by experience. The neuromatrix imparts a pattern--the "neurosignature"--on all inputs from the body, so that experiences of one's own body have a quality of self and are imbued with affective tone and cognitive meaning. The theory is presented with supporting evidence as well as implications for research. PMID- 1303506 TI - Diffuse noxious inhibitory controls (DNIC) in animals and in man. AB - Some neurones in the dorsal horn of the spinal cord are strongly inhibited when a nociceptive stimulus is applied to any part of the body, distinct from their excitatory receptive fields. This phenomenon was termed "Diffuse Noxious Inhibitory Controls" (DNIC). DNIC influence only convergent neurones: the other cell types which are found in the dorsal horn, including specific nociceptive neurones, are not affected by this type of control. In normal conditions, these inhibitions can be triggered only by conditioning stimuli which are nociceptive. The inhibitions are then extremely potent, affect all the activities of the convergent neurones and persist, sometimes for several minutes, after the removal of the conditioning stimulus. In fact, only activity of A delta- or A delta- and C-peripheral fibres can trigger DNIC. DNIC are sustained by a complex loop which involves supraspinal structures since, unlike segmental inhibitions, they can not be observed in animals in which the cord has previously been transsected at the cervical level. The ascending and descending limbs of this loop travel respectively through the ventro-lateral and dorso-lateral funiculi respectively. We proposed that DNIC result from the physiological activation of some brain structures putatively involved in descending inhibition. However, lesions of the following structures did not modify DNIC: Periaqueductal grey (PAG), Cuneiform nucleus, Parabrachial area, locus coeruleus/subcoeruleus, rostral ventromedial medulla (RVM) including Raphe Magnus, Gigantocellularis and Paragigantocellularis nuclei. By contrast, lesions of Subnucleus Reticularis Dorsalis (SPD) in the caudal medulla strongly reduced DNIC. Both electrophysiological and anatomical data support the involvement of SRD neurones in spin-bulbo-spinal loop(s). Indeed, they are unresponsive to visual, auditory or proprioceptive stimulation but are preferentially or exclusively activated by nociceptive stimuli with a "whole-body receptive field"; they encode precisely the intensity of cutaneous and visceral stimulation within the noxious range and are exclusively activated by cutaneous A delta- or A delta- and C-fibre peripheral volleys; they send descending projections through the dorsolateral funiculus that terminate in the dorsal horn at all levels of the spinal cord. In man, exactly analogous results have been obtained by means of combined psychophysical measurements and recordings of nociceptive reflexes. Electrical stimulation of the sural nerve at the ankle simultaneously induces a nociceptive reflex in a flexor muscle of the knee (the RIII reflex) and a painful sensation from the territory of the nerve. Painful heterotopic conditioning stimuli, no matter whether thermal, mechanical or chemical in nature, depress both the reflex and the associated painful sensation, with stronger effects being observed with more intense conditioning stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1303508 TI - [Opioids and the heart]. AB - The possible role of the opioid system in the cardiovascular function is an area that attracted significant attention in recent years. In order to clarify the possible role of opioids in cardiac regulation we have studied the myocardial effects of some opioids and their antagonists. Our results show that in vitro some opioids (dermorphin, alpha- and gamma-endorphins, dalargin and other) may exert inotropic, but not chronotropic, action and may act as modulatory agents on the cholinergic myocardial effects. Some of the opioidergic effects were blocked by naloxone and some were not. The results of pharmacological and physiological analysis show that opioidergic-cholinergic interaction may occur at the postsynaptic myocardial level via different mechanisms. It is well known that in vivo opioids play a significant role in shock and stress; sometimes they act as positive and sometimes--as a negative factor; the mechanisms of these effects are still not clear. We have shown that the endogenous opioid antagonist tetrapeptide FMRFa (Phe-Met-Arg-Phe-NH2) acted as a preservative agent to the acute hypobaric hypoxia and hemorrhagic shock, blood pressure and respiration and also the time of life. The efficacy of FMRFa was higher than that of naloxone. It was suggested that one of the possible mechanism of FMRFa preservative action was the increasing of sympathetic nervous system activity mediated by the endogenous opioid system inhibition. PMID- 1303507 TI - [Role of the GABA system in adaptation to long-term pain stimulation]. AB - Pain syndrome induced by daily peritoneal electrostimulation in rats within two weeks caused decrease in body weight and in motor behavior in open-field test. Moreover, there were a decrease in thymus weight, an increase in adrenal weight and an appearance in most of animals of gastric mucosal erosions. The disturbances of the behavior and somatic state of animals are accompanied by changes of GABA and energy metabolism in the neurons of the frontal cortex. These changes manifested themselves in activation of GABA degradation with simultaneous rise of the succinate--but not isocitrate dehydrogenase activity, inhibition of glutamate dehydrogenase activity and worsening of blood supply to neurons. Chronic (14 days) administration of GABA positive drugs (baclofen--7.5-12.5 mg/kg; depakin--200-400 mg/kg) increases resistance of animals to long-term exposure to pain, which correlates with the normalization of GABA and energy metabolism. Moreover, depakin but not baclofen prevents the development of the microcirculatory disturbances, which is indicated by the normalization of either the activity of sodium phosphatase or the quantity of active capillaries. It is suggested that activation of the inhibitory GABA-ergic mechanisms is a factor of both neuromediatory and metabolic adaptation to the pain. PMID- 1303509 TI - [Stress as an indicator of individual-typologic differences]. AB - Typological peculiarities of the behaviour of adult white male rats were determined using the "emotional resonance" test, i. e. reaction of avoidance of the signals of the defensive state of the other animal of the same species (vocalization, release of pheromones, motor excitation). The rats developed a conditional motor food reflex, and then they were subject to a stress of inescapable pain reaction. Judging by the preserved conditional food reflexes, the rats which avoided the partner's pain screams proved to be the most stable. The rats unable to determine the dominating motivation and incessantly running from one section of the chamber to the other are the least stable. The highest level of catecholamines was found in the blood of the latter group. The sensitivity to the partner's signals of defensive excitation correlates with the degree of such shifts, occurring under the stress influence as the content of noradrenaline, dopamine and 5-oxyndolacetic acid in the tissues of the brain, the state of the lipid component of the cerebral membranes. According to the obtained results the stress reveals the individual peculiarities of the physiological functions which are not obvious without the stress influences. The animals, highly sensitive to the signals of the partner's emotional state, possess high resistance to the action of the most various stresses. It can be assumed that thanks to such stability natural selection preserved the capacity for zoosocial "empathy"--phylogenetic predecessor of human altruism. PMID- 1303510 TI - [Stress: postulates, analysis in terms of the general theory of functional systems]. AB - Further developing of the general theory of stress, put forward by Selye, the theory of functional systems treats stress, of any origin, as a systemic response of the organism to a conflict situation. The theory of functional systems regards, along with the action of stressors, the conflict behavioral situation in which the subjects are deprived of a possibility to satisfy their main requirements, i. e. attainment of useful adaptation results, as the leading cause of stress. It is the conflict behavioral situation that gives rise to the primary reaction of the organism, viz. psychoemotional stress. Cerebral mechanisms of emotional stress in terms of the theory of functional systems are primary in the pathogenesis of psychomotor disorders in stress. The specific neurochemical changes in the limbico-reticular structures of the brain, certain neurochemical disintegration of the neuronal elements, constituting the limbico-reticular structures of the brain, underlie emotional stress. Our experiments showed that predisposition to emotional stress is accounted for by the decreased level of catecholamines and certain oligopeptides such as substance PI (?), beta endorphins, peptide, causing delta-sleep in the limbico-reticular structures of the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303511 TI - [Etiopathogenesis of information disease]. AB - On the basis of the results of animal experiments and observations of people the concept of the information disease was formulated. It is understood as a form of psychoneural pathology characterized by special causes bringing it about, as well as by a number of peculiarities of its manifestation and pathogenesis. Besides, the information diseases, as any nosological form, is characterized by distinct protection mechanisms. The methods of prophylaxis and treatment, based on the specifics of its pathogenesis, were developed in animal experiments and effectively tested on humans. The information disease (ID) is understood as various disturbances of the higher functions of the nervous system, as well as resulting from it, disturbances of the functioning of the other systems of the organisms, occurring because of the brain being for a long time in the conditions of unfavorable combinations of the three following factors, i. e. certain volume of information to be processed for an important decision to be made, the factor of time assigned for the brain work and the level of motivation determining the importance of information and necessity of its being processed. The combination of these three factors can be unfavourable if: 1) it is necessary to process a large volume of information, including the function of decision making, in the conditions of prolonged deficit of time assigned for such work of the brain with the high level of behavioral motivation, or 2) there is information deficit during a long period of time, and the behavioral motivation is also high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303512 TI - [Brain structure as a basis for its reliability]. AB - The construction and activity of the brain are characterized by high degree of the reliability. Some structural-functional premises of the reliability have been described: 1) the superfluity of the nervous elements of many brain structures, which guarantees the brain reserve properties in norm and in different forms of pathology: 2) growth in the mammals row the factors of the superfluity and plasticity of the macro- and microlevels of new evolutionally cerebral systems organization; 3) the multifunctionality peculiar to diverse brain systems different degree. The study of neurochemical bases of reliability in norm and pathological conditions has now a special meaning (by stimulation of corresponding natural transmitter brain systems). The measure of reliability, its "reverse side", is the idea of the brain vulnerability. Some indices of the vulnerability increase in comparative animal row to the man, especially in the sensory and vegetative spheres. PMID- 1303513 TI - Comparison of marginal adaptation between direct and indirect composites. AB - The evaluation of composite resin as a posterior restorative material has been slow and attended by several problems. Gap formation has been considered a serious problem by many researchers. The purpose of this in vitro study is to compare the marginal adaptation of posterior composite resins placed by a direct method with those placed by an indirect method utilizing flexible dyes. Conclusions drawn from the results of this study are that both techniques produced marginal gaps. Also there were no differences in the width of marginal gaps in the composite resin restorations placed by our direct or indirect methods, and no marginal gap differences were observed as a result of anatomical location. PMID- 1303514 TI - Occlusal margin defects around different types of composite resin restorations in posterior teeth. AB - Using stone replicas of individual restorations from a clinical study investigating three types of posterior composite resins, four types of defects were identified on the occlusal margins. It was observed that particular types of defects were commonly associated with each type of composite resin. The microfilled composite usually exhibited crevice formation (marginal fracture), the small-particle hybrid showed evidence of both wear and crevice formation, and a coarse composite resin most noticeably exhibited wear. Fracture of excess composite was associated with the fine-textured composites. PMID- 1303515 TI - Interfacial morphology of an adhesive composite resin and etched caries-affected dentin. AB - The interfacial structure between an adhesive composite resin and dentin after caries removal and acid conditioning was investigated. The hybrid layer between the adhesive resin and surface-demineralized dentin was found to be wider in the area of empty tubules compared with that of the occluded tubules, and was found to be the thinnest at the lateral walls of the cavity where the dentinal tubules run parallel to the cavity surface. Thus, the extent of demineralization by acid conditioning as well as impregnation of resin into the intertubular dentin forming the hybrid layer is probably related to the degree of closure and direction of the dentinal tubules. PMID- 1303517 TI - Dental amalgam: success or failure? AB - A review of recent literature suggests that reasons for amalgam failure can generally be identified and avoided. These include: retentive failure, marginal breakdown, fracture of the tooth or restoration, reasons for sensitivity, poor surface characteristics, and contributions to periodontal disease. Materials themselves are least often the source of problems; rather, most of the failures can be attributed to lack of attention to detail in cavity preparation and handling of the materials. PMID- 1303516 TI - The effects of acid etching on the pulpodentin complex. AB - Acid etching of dentin is used by many bonding systems to remove the smear layer and permit bonding directly to the dentin matrix. Although early animal studies indicated that acid etching caused moderate to severe pulpal reactions, there is a high probability that the pulpal irritation may have been due to microleakage of bacteria and their products. As these reactions are not seen following acid etching of dentin using newer dentin bonding systems, it is clear that one can acid etch dentin if, and only if, one can seal the dentin with subsequently placed bonding systems. Because acid etching increases dentin permeability and dentin wetness, successful bonding of adhesive resins to acid-etched dentin requires the use of hydrophilic resins that bond equally well to both peritubular and intratubular dentin. Future trends seem to be toward lowering both the concentration of acids and the time of etching of dentin. While all bonding systems should be carefully scrutinized prior to marketing, the future looks very promising for the use of adhesive resins on acid-etched dentin. PMID- 1303518 TI - Promotion and tenure: a point of view. PMID- 1303519 TI - Zen and the art of clinical judgment. PMID- 1303520 TI - Oral health of children with congenital cardiac diseases: a controlled study. AB - Congenital cardiac disease (CCD) is one of the most common developmental anomalies in children. Affected children require special care in dentistry because of their susceptibility to infective endocarditis from oral infections, yet little information is available on the oral health of children with CCD. The present study, which investigated 39 children with CCD and 33 healthy control siblings, showed that CCD children generally suffered poorer oral health. In patients with primary dentitions, 52% of CCD children had enamel hypoplasia, compared with only 23% in the control group. In addition, CCD children had significantly more teeth with untreated dental decay (mean dmft 4.2 vs. 2.3), and more endodontically treated teeth. Children with CCD also had less than optimal professional and home dental care. Only 31% had professional advice regarding increased preventive dental health behavior, and only 15% used fluoride supplements, although the children resided in a nonfluoridated area. Furthermore, significantly fewer CCD children had parental help with tooth brushing compared to control children. This study shows that children with CCD should be targeted for vigorous preventive dental care. PMID- 1303521 TI - Parent child separation during dental care: a survey of parent's preference. AB - Seventy-nine parents were surveyed to determine if they preferred to be present when their children underwent dental care. The participants were asked to complete a closed-ended questionnaire before the visit. Sixty-six per cent of the parents wanted to be present with their child for care. Of the parents wishing to accompany their children, 85% responded that they would feel better, and 92% believed the child would feel better. Of the 34% of parents who did not wish to be present, most felt that their children were old enough to receive treatment by themselves (82%), or their presence might cause the child to misbehave (63%). There was no significant difference (P < .01) between the two groups concerning military status, education level, parent's age, parent's previous dental experience, or having other children in the family. Sixty-seven per cent of the parents previously had accompanied their children into the dental operatory. Generally, parents who wanted to be present had younger children, or children making an initial dental visit. PMID- 1303522 TI - The detection of oral Candida in pediatric leukemia patients. AB - Among leukemia patients, a significant number of deaths are due to Candida septicemia, many of which are associated with previous oral infections. Oral candidiasis detection methods vary, and the relationship between oral candidiasis and Candida colonization (CC) is not well defined. The main objectives of this study were to compare the incidence of CC in a healthy and leukemic population, and also to evaluate the efficacy of three simple and inexpensive methods of detecting oral CC in predicting the occurrence of oral candidiasis. A secondary objective was to portray speciation in the examined populations. Forty-two pediatric leukemia patients and 42 healthy, age-, race-, and gender-matched control patients participated in this study. The three methods of detection were cytological examination of the oral mucosa, and direct culture methods from mucosal smears using Sabouraud's dextrose agar (Becton Dickinson Microbiology Systems, Cockeysville, MD) and Oricult-N (Orion Diagnostica, Espoo, Finland). This study demonstrated an increased prevalence of CC in pediatric leukemia patients with the direct culture method detecting CC in a significantly greater proportion of the population (Oricult-N,P = 0.034; Sabouraud's dextrose agar, P = 0.0036). Candida albicans was the predominant species. Further study is needed to determine the clinical significance of oral CC and its relationship to oral candidiasis and systemic infection in pediatric leukemia patients. PMID- 1303523 TI - The influence of practice type, region, and age on treatment recommendations for primary teeth. AB - The purpose of this study was to investigate dentists' treatment recommendations for interproximal surfaces of primary molars based on the type of practitioner (general dentist or pediatric dentist), geographic location, and age of practitioner. Simulated cases, which included histories and pictures of bite-wing radiographs, were mailed to a random sample of 2000 general dentists and 1000 pediatric dentists. Dentists were asked to select their treatment recommendations for eight cases involving the interproximal surface of a specified primary molar. The return rate was 42% (1245) overall, with 36% (723) from general dentists and 52% (522) from pediatric dentists. An amalgam restoration was recommended most often for these eight cases. Dentists in the age 60+ category and pediatric dentists were more likely to recommend treatment for smaller interproximal lesions. Composite resins were recommended infrequently; however, dentists in the 60+ age category and dentists in the Northeast and Southwest were somewhat more likely to recommend composite resin than younger dentists, or dentists in other geographic locations. Dentists in the 40-49 age range, pediatric dentists, and dentists in the Southwest were the most likely to recommend stainless steel crowns. These simulated cases demonstrate differences and similarities in the treatment recommendations for interproximal lesions on primary molars based on age, practice type, and region. PMID- 1303524 TI - Antibiotic prophylaxis for patients with hydrocephalus shunts: a survey of pediatric dentistry and neurosurgery program directors. AB - A survey of antibiotic prophylaxis recommendations for patients with hydrocephalus shunts was sent to directors of advanced programs in pediatric dentistry and neurosurgery. Recommendations were sought for patients with ventriculoperitoneal (VP) or ventriculoatrial (VA) shunts who were to receive dental care. Most respondents believed that shunt infection (SI) was related infrequently to dental procedures. Pediatric dentists believed that 5.2% of infected VA shunts were related to dental procedures, while neurosurgeons believed the rate to be 3.0% (P < 0.05). There was no difference in perceived risk for VP shunts. Except for the equal risk associated with extractions, pediatric dentists were significantly more likely than neurosurgeons to recommend chemoprophylaxis for patients with VA shunts undergoing invasive dental procedures (P < 0.05). They were more likely to agree with neurosurgeons when VP shunts were involved. Except for the equal risk associated with dental prophylaxis, pediatric dentists and neurosurgeons believed VA shunt patients were at greater risk for SI than VP shunt patients (P < 0.05). Pediatric dentists were significantly more likely to ascribe SI to streptococcal organisms, and recommended penicillin for prophylaxis for both VA and VP shunts (P < 0.01 and 0.025, respectively). Although neurosurgeons believed that staphylococcal organisms were most likely to be responsible for SI (P < 0.001), 60% still recommended using penicillin for shunt prophylaxis following dental procedures. PMID- 1303525 TI - IV sedation in pediatric dentistry: an alternative to general anesthesia. AB - This prospective study was conducted to determine the sedative effects of IV ketamine and fentanyl on vital signs and behavior. Twenty-seven children, classified as ASA I, with a mean age of 34 months, were studied. The dosages of IV ketamine and fentanyl given were 0.5 mg/kg and 0.5 mcg/kg, respectively, approximately every 15-20 min. The pulse rate averaged 125 throughout the case. Blood pressure averaged 112/64. The respiration rate averaged 22 breaths per min. Mean behavior composite scores were 1.9 at the initial examination and 3.3 during treatment. One child vomited during treatment. Post-treatment complications were discomfort in 19% (5), nausea in 22% (6), and vomiting in 15% (4) of the patients. We concluded that IV sedation of precooperative healthy pediatric patients with ketamine, fentanyl, and nitrous oxide/oxygen appears to be a safe and effective sedation modality with minimal side effects when administered and monitored by a qualified anesthetist, offering the practitioner an alternative to general anesthesia. PMID- 1303526 TI - Neonatal palatal appliance: light-cured resin material and flexible design. PMID- 1303527 TI - Primary hyperoxaluria in a pediatric dental patient: case report. AB - A case is presented in which primary hyperoxaluria and oxalosis in a 14-year-old Caucasian female were diagnosed. Generalized root resorption resulted in a remarkable mobility of her maxillary central and lateral incisors, although no bone loss was noted. The management of the patient's dental concerns in this rare heritable metabolic disorder consisted of removing the maxillary incisor teeth and placing two sequential prostheses, which the patient tolerated well. A history of trauma to the maxillary incisors was ruled out, so this case adds previously unreported information to our knowledge about the effect of oxaluria on teeth and oral tissues. PMID- 1303528 TI - Shovel incisors, three-rooted molars, talon cusp, and supernumerary tooth in one patient. PMID- 1303529 TI - Pyogenic granuloma associated with a natal tooth: case report. PMID- 1303530 TI - Distal shoe: a cost-effective maintainer for primary second molars. PMID- 1303531 TI - The clinical section--site visit check list. American Academy of Pediatric Dentistry. PMID- 1303532 TI - An endangered species. PMID- 1303533 TI - Effect of nursing caries on body weight in a pediatric population. AB - A review of anesthesia and sedation records of children with nursing caries was undertaken. The weights of these 115 children with otherwise noncontributory medical histories were compared to subjects matched for age, gender, race, and socioeconomic status. Nursing caries children were treated using either sedation or general anesthesia and received treatment for at least one pulpally involved tooth. Comparison subjects had no gross carious lesions. The average age for both the comparison and test groups was 3.2 years (SD = 1.01 and 0.98, respectively). While comparison patients weighed 16.2 +/- 3.08 kg, patients with nursing caries weighed only 15.2 +/- 2.66 kg. This difference was statistically significant (P < 0.005). Of the nursing caries patients, 8.7% weighed less than 80% of their ideal weight, compared with only 1.7% of the comparison patients (P < 0.02). Of nursing caries children, 19.1% were in the 10th percentile or less for weight, compared with only 7.0% of comparison subjects (P < 0.01). The mean age of "low weight" patients with nursing caries was significantly greater than for patients at or above their ideal weights, indicating that progression of nursing caries may affect growth adversely. PMID- 1303534 TI - Evaluation of morphine as compared to meperidine when administered to the moderately anxious pediatric dental patient. AB - This investigation evaluated two narcotic regimens used to sedate pediatric dental patients who previously demonstrated uncooperative behavior. One consisted of submucosal morphine (0.15 mg/kg), and the other, oral meperidine (2.2 mg/kg); both were administered in combination with oral promethazine (1.1 mg/kg). Patients 2-7 years old were sedated with one of the two regimens and videotaped during dental treatment. If sedation was successful, the child received the other regimen at the next appointment, resulting in a total of 42 sedations in 29 children. Later, patient behavior was rated blindly by two independent observers viewing tapes of specific events during dental treatment. Fourteen of 23 (61%) patients receiving morphine and 11 of 19 (58%) patients receiving meperidine were sedated successfully. Vital signs, including pulse, respirations, blood pressure, and oxygen saturation were monitored and remained stable for both groups. ANOVA for repeated measures showed no significant differences for any vital sign in either group across time. Wilcoxon's signed rank test revealed significant improvement for the patients successfully treated in both groups when presedation behavior was compared with behavior during the events of rubber dam application, operative, restorative treatment, and exit (meperidine, P < 0.005 and morphine, P < 0.001). Improvement also was seen in the meperidine group for the event of local anesthesia (P < 0.01). Chi-square analysis showed no statistically significant differences in effectiveness or safety between the two sedative regimens. PMID- 1303535 TI - Nutrient intake and dental caries in the primary dentition. AB - An extensive literature has assessed the influence of diet on dental caries, but to date dietary influences on caries of the primary dentition have not been studied widely. This study examined the role of specific nutrients in the caries experience of preschool children. A total of 628 children ages 2 to 6 years received a dental examination, parent interview, and a seven-day diet diary. The diary was completed adequately for 269 children (43%). The average daily intakes of 15 nutrients were computed and compared with recommended dietary allowances (RDA); total sugar consumption and Ca/P ratio were calculated. Each child's gender, age, fluoride history, previous dental experience, and nutrient intakes were examined as independent variables. Stepwise logistic regression showed the combination of categories most predictive of caries was older age, suboptimal fluoride consumption, and recall dental visit. No association was apparent between dental caries and the intake of specific nutrients, total sugar consumption, or Ca/P ratio. PMID- 1303536 TI - Effects of phenytoin on dental caries and plaque in Streptococcus sobrinus infected rats. AB - Effects of phenytoin (PHT) administration on dental caries in rats infected with Streptococcus sobrinus 6715 were investigated. Twenty-day-old specific pathogen free Fischer male rats were infected with S. sobrinus 6715 and fed diet 2000 containing 56% sucrose with or without PHT for 52 days. Antibody responses against anti-S. sobrinus in serum and saliva failed to show a statistical difference between PHT-treated and nontreated rats. These results indicate that PHT treatment increased plaque deposition and dental caries in the rats infected with S. sobrinus 6715 and fed diet 2000 containing PHT (1-2 mg/g), as compared with those similarly infected and fed diet without PHT (P < 0.001). PMID- 1303537 TI - Enamel protein in smooth hypoplastic amelogenesis imperfecta. AB - Amelogenesis imperfecta (AI) remains a poorly understood group of hereditary enamel defects characterized by a wide array of clinical presentations. Although numerous reports have described the histological features of AI, knowledge concerning the biochemical composition of the affected enamel remains minimal. The purpose of this investigation was to examine the protein of smooth hypoplastic AI enamel. Exfoliated primary teeth were obtained from an individual with smooth hypoplastic AI together with exfoliated teeth from normal healthy individuals for controls. Enamel was dissected from the AI and control teeth to determine protein content and amino acid profile. The analyses showed that the hypoplastic AI teeth contained 2% protein, compared with 0.3% in normal primary enamel. The protein content of the hypoplastic AI enamel was similar to that reported for the late maturation stage of normal primary enamel. The amino acid profiles of both normal and AI enamel were similar although there appeared to be increased amounts of glycine in the AI enamel. Hypoplastic AI enamel showed an amino acid profile similar to normal mature primary enamel in contrast to hypomaturation AI that exhibits an amelogenin-like character. The amount of retained protein also was different from that reported for hypomaturation AI enamel which contains approximately 5% protein compared with the 2% seen in hypoplastic AI enamel. This study emphasizes the potential usefulness of protein characterization in delineating different AI types and illustrates how this information may lead to an understanding of the developmental defects responsible for producing abnormal enamel. PMID- 1303538 TI - Method of payment for children's dental services by practice type and geographic location. AB - The purpose of this project was to evaluate practice type and geographical differences in methods of payment accepted for children's dental services. A survey was mailed to 2000 general dentists and 1000 pediatric dentists randomly selected to provide representation from the 50 United States. Dentists were asked to specify the type of practice and the state in which they primarily practice. The survey included Medicaid, dental insurance, preferred provider organizations (PPO), and self-payment as payment options. Dentists were asked to indicate whether they never, occasionally, or frequently accepted each option of payment for children's dental services. Responses were received from 1245 (42%) dentists, including 723 general dentists and 522 pediatric dentists. Chi-square statistical analysis revealed significant practice type and regional differences in the acceptance of Medicaid for payment. Pediatric dentists accept Medicaid more frequently than general dentists (P < 0.001). Most dentists accept dental insurance and self-payment, while few indicate involvement with a PPO. The study revealed significant practice type differences only in the acceptance of Medicaid as payment for children's dental services. On a geographic basis, there were significant differences in the acceptance of Medicaid and dental insurance. PMID- 1303539 TI - Correcting ectopic first permanent molars with metal or elastic separators. PMID- 1303541 TI - Neurofibroma of the mandible in an adolescent with von Recklinghausen's disease. PMID- 1303540 TI - Alternative use of the electrical burn appliance. PMID- 1303542 TI - Paying the pauper--ways to reduce student debt. PMID- 1303543 TI - Dental caries in HIV-infected children. PMID- 1303544 TI - Histopathology of the pulp in primary incisors with deep dentinal caries. AB - The purpose of this study was to assess the histological appearance of the pulp of human primary incisors extracted because of deep, unrestorable caries, and to determine how clinical pulp exposures affected the histological status of the pulp compared to nonexposures. Caries was removed carefully from all teeth after fixation; 24 incisors had pulp exposures, and 29 teeth had no pulp exposures. Histological examination showed normal pulps in 69% of the teeth without pulp exposures, compared to 33% of teeth with exposed pulps (P < 0.05). Microabscesses were observed in 33% of cases with pulp exposures, compared to 10% of cases without pulp exposures. In this study, 46 of 53 pulps remained vital in spite of the multiple and deep carious lesions. Teeth without pulp exposures were diagnosed in the treatable category in 20 of 26 cases. PMID- 1303546 TI - Correction of bilateral ectopic eruption of first permanent molars using a fixed appliance. PMID- 1303545 TI - The influence of social status and prior explanation on parental attitudes toward behavior management techniques. AB - The purpose of this study was to determine whether parental social status influences preference toward behavior management techniques used during dental treatment of children. One hundred and twenty-two parents from two private practices and one institutional site completed a questionnaire and rated eight commonly used behavior management techniques. These techniques were tell-show-do, nitrous oxide/oxygen, Papoose Board (Olympic Medical Group, Seattle, WA), voice control, hand-over-mouth (HOM), oral premedication, active restraint, and general anesthesia (GA). Half the parents viewed these eight techniques on a videotape which contained prior explanation for each technique (experimental group). The other half (control group) viewed the same techniques on videotape, but without prior explanations. Parents indicated their degree of acceptability by marking a line on a visual analogue scale (VAS, scored from 1 to 99). A score below 50 was considered acceptable. The parents were divided into "high" and "low" social status groups. Significant differences for HOM and GA were noted between mean scores of the experimental and control groups for both "high" and "low" social status groups; the control groups were less accepting except for GA in the "low" group where the reverse was true (P < 0.05). Techniques judged least acceptable were HOM, GA, Papoose Board and oral premedication. Parental acceptance of individual techniques varied greatly, suggesting the importance of informed consent irrespective of social status. PMID- 1303547 TI - The use of fluoride-containing toothpastes in young children: the scientific evidence for recommending a small quantity. PMID- 1303549 TI - Symptomatic benign migratory glossitis: report of two cases and literature review. AB - Benign migratory glossitis (geographic tongue) is a common clinical finding in routine pediatric dentistry. The condition usually discovered on routine clinical examination, appearing as an asymptomatic, ulcer-like region on the dorsum of the tongue. The lesion may recur at different sites on the tongue, creating a migratory appearance, and in many cases, will resolve completely. The presentation of symptomatic geographic tongue in children is rare. This article presents two cases of symptomatic geographic tongue. Both children presented with a chief complaint of significant oral pain which was affecting daily activity, eating, and sleeping. Both patients presented with a classical clinical presentation of ulcer-like regions on the dorsum of the tongue in which the filiform papillae were denuded. Successful management was achieved with topical and systemic antihistamine. The clinician should be aware that this condition may be symptomatic in children. PMID- 1303548 TI - A pilot study of preschoolers' use of regular-flavored dentifrices and those flavored for children. AB - Ingestion of fluoride dentifrice by preschool children recently has been implicated as a risk factor for dental fluorosis. The availability of dentifrices flavored for children could increase fluoride ingestion by young children at risk for dental fluorosis. This article reports results of a pilot study of use of regular-flavored dentifrice and those flavored for children among 29 preschool children. Using a crossover design, larger quantities of fluoride dentifrice specially flavored for children were used compared with the quantities of regular flavored dentifrice. Pediatric dentists and other health care providers should advise parents to supervise preschoolers' toothbrushing. Preschoolers should use only small, pea-sized quantities of dentifrice to avoid increased risks of dental fluorosis. PMID- 1303550 TI - Fused primary incisors with succedaneous supernumerary in the area of a cleft lip: case report. PMID- 1303551 TI - Microdontic teeth succedaneous to natal teeth: a report of two cases. PMID- 1303553 TI - Charges for sealants and one-surface, posterior permanent restorations: three years of insurance claims data. PMID- 1303552 TI - Ewing's sarcoma of the mandible in a young patient: case report. AB - Ewing's sarcoma, a malignant tumor, rarely occurs in children younger than 5 years of age. Although it may appear in any bone, it is more common in the axial skeleton, rarely involving the jaws (1 to 2% incidence, mostly in the mandible). The most common symptoms are pain and swelling in the affected area. History of trauma often is reported. The case of a 4-year, 10-month-old Caucasian male with a rapidly expanding mass on the right side of his face following an injury to his mandible is reported. PMID- 1303554 TI - [Antiphospholipid antibodies and the central nervous system]. AB - Among anti-phospholipid antibodies (APA), anti-cardiolipin antibodies and lupus anticoagulants are associated with arterial and venous thrombo-embolic manifestations. Antiphospholipid antibodies can be secondary to numerous diseases, especially systemic diseases, but they are usually encountered in the primary antiphospholipid syndrome. Neurological manifestations associated with APA are most often, if not always, ischemic in nature: large or small subcortical, often multiple, infarcts and transient ischemic attacks are the usual clinical presentations. Several mechanisms can lead to cerebral ischemia in the primary antiphospholipid syndrome, and their diagnosis is probably important for therapeutic choices. A prospective controlled study has started, which should provide data on the prognosis and management of this syndrome. PMID- 1303555 TI - [Cerebrovascular complications of cancers]. AB - About 15% of patients with cancer have cerebrovascular lesions, resulting from 4 kinds of disorders sometimes intermingled in advanced disseminated cancer: coagulation disorders, direct effects of the tumor, infections and therapeutic measures. Infarction, hardly less frequent than hemorrhage, mostly complicates lymphoma and carcinoma. Hypercoagulation states, such as chronic disseminated intravascular coagulation, nonbacterial thrombotic endocarditis, and nonmetastatic cerebral venous thrombosis account for about 50% of cases. Tumor emboli, as seen in intravascular malignant lymphomatosis, arteritis related to aspergillus, granulomatous angiitis with or without herpes zoster and radiation induced atherosclerosis are rarer. Cerebral hemorrhages, excluding bleeding from the metastases of choriocarcinoma and melanoma are mainly associated with leukemia by acute disseminated intravascular coagulation as in promyelocytic leukemia, by leukostasis or by pancytopenia. Both infarction and hemorrhage rarely reveal the neoplasia. Lesions are often small and disseminated, and therefore produce a picture of diffuse acute or subacute encephalopathy rather than acute focal deficits. Finally, there may be no relationship between the cerebrovascular event and the neoplasia, and atherosclerosis or traumatic subdural hematoma may well be the causal factor. PMID- 1303556 TI - [Interhemispheric transfer in multiple sclerosis. Morphofunctional correlations]. AB - Signs of cerebral disconnection, especially left ear suppression to dichotically presented verbal stimuli, have been reported in multiple sclerosis patients and found to be correlated to morphological atrophy of the corpus callosum on magnetic resonance imaging. To reinvestigate this issue, 26 patients satisfying criteria for definite multiple sclerosis were proposed 3 tasks aimed at evaluating interhemispheric function: a dichotic listening task, a motor finger tapping task and a sensory transfer task. Performance at these tasks suggested impaired callosal function in MS patients, compared to normal controls. Callosal morphology was assessed on midsagittal MRI sections using a digitalised method of partition of the callosal area into 6 subregions and automatized surface measurements. Results of correlations between task performance and callosal areas showed a significant correlation between total callosal atrophy and severity of interhemispheric impairment on each functional task. Moreover, impaired motor transfer was specifically related to atrophy of the anterior callosal regions. These results suggest that MS patients may constitute a suitable population to studying interhemispheric transfer of information through the callosal commissure and that this approach may be useful in the clinical management of MS patients. PMID- 1303557 TI - [Dopa-sensitive dystonia]. AB - Dopa-sensitive dystonia has been recognised for twenty years. It may occur in the first years of life. It first affects the lower limbs, then generalized becomes, as in torsion dystonia. Eight clinical cases are presented in five boys and three girls. The absence of the disorder in the parents, but its presence in siblings in three cases suggests that it might be recessively inherited. The symptoms are severe enough to cause major functional disability. In some cases, the intensity of the motor disorder varies during the days being, less pronounced in the morning or after a nap and more marked in the evening. Nonetheless, this feature is not constant and thus cannot be considered as an essential diagnostic criterion. Treatment with levodopa gives remarkable and durable results, but it must be continued indefinitely. Abnormal movements accompany an overdose but regress when the dosage is decreased. Unlike Parkinson's disease, it is not necessary to increase or fragment doses to avoid fluctuations in the efficacy of treatment during the day. On the contrary, after several years of the illness a decrease in daily dosage sometimes to a single dose is possible. Discontinuing treatment leads to reappearance of dystonia after two or three days. There are no established biological criteria to aid diagnosis. However, a decrease in urine levels of homovanillic acid was observed in two cases. Dopa-sensitive dystonia should be regarded as distinct from juvenile Parkinson's disease, firstly because of its symptomatology and secondly, and more importantly, because of its particular course, since fluctuations in therapeutic efficacy are never observed. It is the only known example of dopaminergic insufficiency that is chronically almost completely controlled by a modest exogenous supply of levodopa. PMID- 1303558 TI - [Central pontine myelinolysis after hepatic transplantation]. AB - We report two cases of central pontine myelinolysis (CPM) following liver transplantation. The incidence may well be underestimated as in the past the diagnosis of CPM was based on postmortem findings. Malnutrition, poor clinical condition, encephalopathy are common features of transplanted patients developing CPM. The clinical course is characterized by a biphasic pattern; after normal recovery from anesthesia, there is a subsequent and gradual deterioration in the neurological state. The complex syndrome associates loss of consciousness, flaccid quadriplegia and pseudobulbar palsy. Among the many factors suspected of inducing CPM, a rapid correction of natremia (> 12 mmole/l/day) seems most probable. With regards to liver transplantation, CPM presents rather specific problems. Delaying transplantation to correct hyponatremia carries a risk of severe hepatic encephalopathy. On the other hand, the intraoperative compensation of blood losses with high sodium content blood products tends to induce an abrupt rise in sodium serum concentration. Moreover, renal capacity to excrete sodium is often impaired, due to hepatic insufficiency and surgical procedure. Transplantation should not be delayed, but as infusion of large amounts of sodium cannot be avoided (fresh frozen plasma, human albumin, red blood cells), natremia may be controlled by continuous veno-venous hemofiltration with low sodium content substitution fluids. PMID- 1303559 TI - [Pseudoradicular syndrome in multiple sclerosis. 4 cases diagnosed by magnetic resonance imaging]. AB - Four patients with multiple sclerosis presented with pseudoradicular limb pain. There was a limb weakness with sensory loss and areflexia. Magnetic resonance imaging showed a demyelinating plaque in the cervical cord with a characteristic T2 relaxation time. A direct relationship between the plaque and the clinical troubles was established in all cases. Treatment with corticosteroids was helpful, and other treatments (carbamazepine) were not necessary. The mechanisms of such pain are unknown but some of the symptoms may be the result of lesions in the endogenous pain control system. PMID- 1303560 TI - [Polysaccharide amylopectin-type storage myopathy]. AB - We report a late onset form of polysaccharide myopathy with progressive limb girdle muscles weakness, without cardiomyopathy. Muscle biopsy showed a vacuolar myopathy in type 1 fibres. The PAS positive diastase resistant deposits were made of filamentous material at electron microscopy similar to long chain glycogen. Muscle glycogen levels and glycogen metabolism enzymes were normal. Numerous abnormal mitochondrial with paracrystalline inclusions were observed around the storage material. Twelve patients with polysaccharide amylopectin-like storage myopathy have previously been reported. This disease must be distinguished from other diseases with polysaccharide accumulation such as branching enzyme deficiency and some cases of phosphofructokinase deficiency. In other disorders, no deficient enzymes in the glycogen pathway was found. Some of them show systemic storage (Lafora disease, adult polyglucosan body disease). Corpora amylacea, Bielchowsky bodies and basophilic degeneration of the myocardium represent localised depositions. A few inclusions can also be observed in hypothyroid myopathy. In polysaccharide myopathy allosteric inactivation of phosphofructokinase by a mitochondrial dysfunction is considered by analogy with cases of polysaccharide storage related to phosphofructokinase deficiency. PMID- 1303561 TI - [Orbital apex syndrome disclosing naso-oculo-cerebral zygomycosis]. AB - In a 70-year-old male patient with untreated diabetes a febrile orbital apex syndrome of rapid onset revealed a rhino-orbito-cerebral zygomycosis. Biopsies of the ethmoidal mucosa showed numerous colonies of the Rhizopus genus. Despite medical treatment (amphotericin B) and surgery (ethmoidectomy), the patient died within one week. Rhino-cerebral zygomycosis is a rare disease which occurs in diabetic and immunocompromised patients. PMID- 1303562 TI - [Value of intravenous immunoglobulins. A case of Guillain-Barre syndrome]. AB - A case of severe Guillain-Barre syndrome (GBS) was treated with high dose intravenous immunoglobulin (IVIG), 400 mg.kg-1.days-1, over three consecutive days. The treatment was repeated once. We observed a time-related response between immunoglobulins administration and clinical improvement. The pathologic lesions of the GBS suggest that this syndrome has an immunologic basis: a humoral factor is probably not the only immunological mechanism and cellular mechanisms are also likely to be of importance. Specific mechanisms might also be present in GBS, such as anti-idiotypic suppression of autoantibodies, and elimination of circulating immune complexes. Treatment with IVIG might have several therapeutic advantages over plasmapheresis: IVIG is easily infused without any delay, is easily available and has been used widely without serious complications. PMID- 1303563 TI - [Trigeminal neurotrophic ulcer and vascular disorders of the brain stem. A clinico-electrophysiological study]. AB - Torpid facial ulcerations may occur as a result of lesions involving the trigeminal fibers. These neurotrophic ulcerations have usually been observed after alcohol injection in the trigeminal ganglion. We report two cases associated with brainstem infarction. In both patients, the blink reflex was studied. The masseter inhibitory reflex was studied in one case. Analysis of these electrophysiological recordings can be of particular value in localizing the site of the lesion along the trigeminal pathway. PMID- 1303564 TI - [Acute anterior bi-opercular syndrome of critical origin in epilepsy with rolandic spikes]. AB - We report the fifth case of a palsy of the lips, the tongue and the pharynx corresponding to an acute pseudo-bulbar syndrome causing speech arrest, and hyper sialorrhea. The clinical examination and the electroencephalograms showed a partial motor status with spikes discharges in the two central regions, in a 10 year old boy known to have epilepsy with rolandic spikes. The status epilepticus ceased with phenytoin therapy. Although epilepsy with rolandic spikes is a benign one without any cerebral lesion, a partial motor status epilepticus is possible and does not change prognosis. PMID- 1303565 TI - [Cholesterol emboli with neurologic manifestation in the spinal cord]. AB - A 71-year old man presented with a progressive chronic paraparesis combined with inflammatory biological features including hypereosinophilia and an aneurysm of the abdominal aorta. Disseminated cholesterol embolization of arterioles was evidenced by the identification of cholesterol crystals in biopsies of the quadriceps muscle and of an iliac lymph node. Despite the lack of post mortem study of the spinal cord, the presentation was highly suggestive of cholesterol emboli in the spinal arteries. Only ten documented cases have been reported. PMID- 1303566 TI - [Presentation at the Salpetriere hospital. November 1990. Dysarthria,disorders of gait and intellectual activity, hepatomegaly in a 67 year-old woman]. PMID- 1303567 TI - [Bilateral thalamic glioma. A clinicopathological study of 2 cases]. AB - Two cases of bilateral thalamic glioma in a 70 year-old man and a 8 year-old boy, documented by MRI and pathological data are reported. Such tumors are rare. Early symptoms may be misleading, with intellectual impairment or psychiatric disorders together with a normal CT scan. MRI and pathological findings support the view that bilateral thalamic gliomas represent a particular clinico-pathological entity among thalamic tumors. PMID- 1303568 TI - [Cerebral infarction, placoid epitheliopathy and sarcoidosis]. AB - We report a case of cerebral infarction in the basal territory of the left middle cerebral artery, associated with acute posterior multifocal placoid pigment epitheliopathy, most probably due to sarcoidosis. Neurological symptoms resolved spontaneously without sequelae. We discuss the relationship between acute posterior multifocal placoid pigment epitheliopathy, sarcoidosis and cerebral granulomatous angiitis. PMID- 1303569 TI - [Chronic polyradiculoneuritis. 25 cases]. AB - Twenty-five patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were studied in order to define the clinical, biological, electrophysiological and pathological features of this disease. There were 11 men and 14 women ranging in age from 15 to 82 years. The average follow up was 43 months. Patients fulfilled the criteria laid down by Dyck et al. (1975), except that progression of weakness was at least 2 months and not 6. Fourteen patients had a progressive course and 11 a relapsing one. Weakness was almost constant (24/25), sensory impairment was present in 22/25 with deep sensation predominantly impaired. Areflexia was observed in all patients. A history of previous infection or other possible precipitating event was given by 7 patients. Cerebrospinal fluid examination showed a raised total protein count in 22 cases. Electrophysiological examination revealed a slowing down of nerve conduction velocities to an extent compatible with a demyelinating process in 23 cases; 2 patients only had prolongation of F-waves. Sural nerve biopsy was less informative: inflammatory process--the most specific finding--was observed in only 3 out of 20 biopsies. Six patients had benign forms or spontaneous remission, the others were treated with corticosteroids or with immunosuppressive drugs. Most patients (64%) recovered very well. Only one died during the time of study. Eight other patients were treated with high-dose intravenous immunoglobulins and 4 of them improved with administrations at regular intervals to maintain the benefits observed. The occurrence of CIDP in association with other conditions is reviewed and we discuss its nosological position among the acquired demyelinating neuropathies. PMID- 1303570 TI - [Candida albicans meningitis and neurosarcoidosis]. AB - We report a clinico-pathological case of neurosarcoidosis characterized by chronic meningitis, intracranial hypertension, bilateral optic atrophy, arthritis and enlargement of liver and lung hilar nodes. Synovial and supraclavicular node biopsies showed multiple non caseating nodules without tubercle bacilli, Candida albicans and Cryptococcus neoformans. Post-mortem examination showed a severe meningeal lymphoplasmocytic infiltration with numerous non-caseating nodules, several giant cells and presence of Candida albicans. There were also a periventricular infiltration of similar cells and numerous cerebral and cerebellar infarctions. We think that the Candida albicans meningitis was a consequence of the immunodepression of sarcoidosis and of corticosteroid therapy. PMID- 1303571 TI - [Epileptic crisis during and after cerebrovascular diseases. A clinical analysis of 78 cases]. AB - Seventy-eight patients with post-stroke seizures were studied retrospectively to determine the clinical, EEG and CT features of these seizures and their prognosis. There were 57 cerebral infarctions and 21 hemorrhages. Twenty-eight (36%) initial seizures occurred within one month after the stroke (0-24 hours in 19 cases) and were classified as early-onset seizures. Fifty (64%) initial seizures occurred more than 3 months after the stroke (3-12 months in 33 cases) and were classified as late-onset seizures. Compared with a population of 1938 strokes admitted during the same period, the proportion of patients with alcohol abuse, infarction in the anterior cerebral artery territory, watershed infarcts and lobar haemorrhages was significantly greater in our series. The proportion did not vary with the nature of the stroke (infarction or hemorrhage), except for early onset seizures in which the proportion of hemorrhages was significantly greater. Nor did it vary with the cause of hemispheric infarctions (cardioembolism or atherothrombosis or others). Ninety-five percent of the lesions affected the cerebral cortex or the subcortical white matter or both. Of all 78 initial seizures, 64% were partial motor (simple or secondarily generalized); 32% were primarily generalized, and 4% were partial not motor; status epilepticus was seen in 14% of the cases. An initial EEG, performed in 76 patients was normal in 7. Among the remaining 69 patients EEG showed focal or diffuse slowing down in 63% and epileptic features in 37% (including 10 cases of PLEDs). Early post-seizure EEG and repeated recordings significantly increased the specificity of EEG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303572 TI - [Cerebral complications of incontinentia pigmenti. A clinicopathological study of a case]. AB - A baby born with the typical features of incontinentia pigmenti, developed convulsions from the 5th day onward. CSF was normal. CT scan showed diffuse hypodensities in the left hemisphere. The baby died at 2 months of age of primary pulmonary hypertension. The neuropathological examination showed a normal morpho histogenesis of the brain. There were necrotic, non inflammatory changes in the cortex and white matter, which did not affect a vascular topography. The lesions appeared to have occurred in the neonatal period and were markedly predominating in the left hemisphere. PMID- 1303573 TI - [Long-term treatment of Lambert-Eaton syndrome by 3, 4 diaminopyridine]. AB - A patient with a 5 year history of slow-progressive Lambert-Eaton Myasthenic Syndrome (LEMS) was treated for a period of 12 months with 3,4-diaminopyridine (3,4-DAP). The therapy led to an objective increase in muscle power. During the treatment period, there was no increase in muscle weakness, but attempts at withdrawal of the drug confirmed a progression. The mouth dryness disappeared and autonomic regulation disturbances were improved. All of the laboratory parameters remained unchanged. A neoplasia was excluded by extensive endoscopic and radiological investigations. Side-effects included initial perioral paresthesia and, later, paresthesia down the skin and along the ulnar edge of the forearm. 3,4-DAP seems to be an effective and acceptable long-term symptomatic therapy in LEMS. PMID- 1303574 TI - [Cerebral ischemic accidents and tuberculous meningitis]. AB - Two cases of tuberculous meningoencephalitis mimicking regressive or transient ischaemic attacks or migraine with aura are reported. The value of MRI with gadolinium in demonstrating inflammation of the leptomeninges, of transcranial Doppler sonography in detecting segmentary accelerations in the basal cerebral arteries suggestive of arteritis and of CSF examination with polymerase chain reaction (PCR) are emphasized. PMID- 1303575 TI - [Thrombosis of the upper longitudinal sinus and syphilitic cranial osteitis]. AB - A 33-year old man developed progressive intracranial hypertension with papilloedema due to thrombosis of the superior sagittal sinus (SSS) by extension of a skull osteitis. Serological tests for syphilis were positive in blood, CSF and synovial fluid. Under treatment with penicillin and corticosteroids signs of intracranial hypertension and CT scan abnormalities disappeared. SSS thrombosis persisted at angiographic control. PMID- 1303576 TI - [Hemichorea-hemiballismus and toxoplasmosis in AIDS]. AB - The authors report two cases of hemichorea-hemiballism revealing a toxoplasmic abscess in the subthalamic nucleus during AIDS. Despite the great frequency of this opportunistic infection such cases are exceptional. This rarity seems to be explained by the frequent association of other lesions of the basal ganglia which may prevent the movement disorders. Nevertheless an hemichorea-hemiballism in young people must suggest a cerebral toxoplasmosis. Finally a symptomatic treatment is often necessary; in these cases the use of sodium valproate must be considered, this drug being able to induce a clinical improvement. PMID- 1303578 TI - [What are the limits for surgical treatment of bronchogenic cancer?]. PMID- 1303577 TI - [Intracranial dural arteriovenous fistula with spinal venous drainage]. AB - Two cases of intracranial dural arteriovenous fistulae draining into the medullary veins are reported. One patient was a 68-year old man who experienced brief and repeated episodes of paraplegia, followed by a permanent spinal cord syndrome. The other patient was a 74-year-old woman who rapidly developed a syndrome of the medulla and spinal cord. In both cases spinal cord angiography failed to show vascular malformations, but myelography revealed venous imprints and magnetic resonance imaging of the cervical spinal cord disclosed a pre medullary signal. Cerebral angiography showed an intracranial arteriovenous fistula fed by the external carotid artery and draining into the veins of the posterior fossa and the spinal venous network. Complete occlusion of the fistula was achieved by embolization with microparticles. Intracranial dural arteriovenous fistulae draining into the medullary veins are rare: to our knowledge, only 4 cases have been reported. Such lesions must be considered whenever a spinal cord syndrome has no detectable cause. PMID- 1303579 TI - [Surgery for cancer with mediastinal lymph node invasiveness (N2)]. AB - Resection is indicated in about 20% of N2 cases. When it is complete a 5-year survival rate may be expected. It represents for these patients a chance of cure and therefore must be considered in all cases of N2, either immediately or after an adjuvant treatment. Its results can be improved by strict selection of the patients and by an efficient chemotherapy. PMID- 1303580 TI - [Surgery of cancers extending to the carina]. AB - When small and inextensive these tumours are rare and often surgical; when extensive they are usually unresectable. Owing to the late development of dyspnoea and to the frequent normality of thoracic radiography the endoscopic diagnosis is seldom made at an early stage, which explains why these tumours are often regarded as non surgical. In limited forms the best treatment is resection of the carina with or without reconstruction of the tracheal bifurcation, but this surgical procedure is frequently difficult. However, this type of surgery has benefited from modern imaging for the preoperative evaluation, of advances in anaesthesia and ventilation techniques for the operation itself, and from changes in techniques and strategies by medico-surgical teams specialized in pneumology. The results of this surgery are difficult to evaluate due to the absence of published homogeneous series. PMID- 1303581 TI - [Transcervical excision of bronchopulmonary cancers with apical invasiveness]. PMID- 1303582 TI - [Conservative treatment of bronchogenic cancers: lobectomy with excision anastomosis and limited excision]. AB - Lung cancer resection surgery often reduces the respiratory function to the point that it can preclude pneumonectomy or even standard lobectomy. When these usual operations are impossible for functional reasons more restricted procedures can be performed, local conditions permitting. Thus, lobectomy with resection anastomosis may be a suitable alternative to pneumonectomy, and segmental resection may be considered when standard lobectomy is rejected. However, this conservative surgery can be envisaged only when it does not risk to affect the quality of the long-term results. While lobectomy enlarged to the bronchial tree has proved to be justified for the treatment of cancers without lymph node invasion, limited resections give uncertain results and must be regarded as an alternative to surgical abstention. PMID- 1303583 TI - [Surgery of bronchogenic cancer in aged patients]. AB - The lung cancer mortality rate increases with age, but the progressivity and radioclinical features of this cancer in the elderly are not very different from those observed in younger subjects. As in these subjects, the pretherapeutic evaluation must be complete whenever surgery seems to be possible, but special attention must be paid to the cardiovascular system. Several recent studies have reported postoperative mortality and morbidity rates paradoxically similar, or even lower, in both old and relatively young patients, probably because of a better selection. Moreover, the survival rate at 5 years of the elderly compares favourably with that of younger subjects. Thus, age is not an absolute contra indication to surgery, but it requires a more rigorous selection and a closer postoperative supervision. PMID- 1303585 TI - The evolution of dental technology. PMID- 1303584 TI - [Complications and mortality of surgery for bronchogenic cancers]. AB - Resection surgery for lung cancer is beset with specific or non-specific complications which often darken the prognosis for life. The specific complications, related to surgical dissections, are mainly per- and postoperative haemorrhages of various origins and, less frequently, disturbances in respiration, nerve wound or chylothorax. Soon after pneumonectomy a bronchial fistula encouraged by different factors may appear (3.3% of the cases) and empyema, usually caused by staphylococci, may develop (3%). Non-specific complications may disturb the post-resection period, involving the lungs (atelectasia, parenchymal infections, acute respiratory failure) or the cardiovascular system (pulmonary embolism, dysarrhythmia). The overall perioperative mortality rate has decreased with time owing to advances in anaesthesia and intensive care: in the hands of certain medico-surgical teams it does not exceed 3%. It is significantly lower in lobar (mean: 4.5%) than in pulmonary (mean: 8.4%) resections. Enlarged resections and lymph node dissections are aggravating factors. Patients aged 70 or more do not tolerate these operations so well: their mean overall mortality rate is twice that observed in younger patients (8% on average and up to 20%). Resection surgery for lung cancer remains a necessarily hazardous procedure but is the only treatment that can cure the patient. Its success is directly conditioned by a good preoperative risk evaluation. PMID- 1303586 TI - Tips for successful all-ceramic restorations. PMID- 1303587 TI - Transforming remakes into demonstration models. PMID- 1303588 TI - The future of our profession. PMID- 1303589 TI - The effect of ATP on Ca(2+)-dependent K+ channels of human red cells. AB - The action of ATP on Ca(2+)-dependent K+ channels was studied in fresh human erythrocytes using patch-clamp techniques. Single-channel current was recorded at pH 6.5 from inside-out patches in the presence of symmetrical K+ gluconate solutions, containing both 1 microM free Ca2+ in the bath and 0.5 mM LaCl3 on the pipette side. With no ATP, the electrical activity revealed low-conductance K+ channels (25 pS), which showed inward rectification and an opening kinetics dependent on membrane potential. When ATP (1 mM) and Mg2+ (2 mM) were added together and a depolarizing potential was simultaneously applied, only a high conductance channel (about 75 pS) was observed. This channel showed no rectifying properties and it was not found if ATP was added in the absence of Mg2+. Channel activity was enhanced by adding fluoride (10 mM) or trifluoperazine (50 microM) whilst it was reduced after incubating with dibutyryl cAMP (50 microM) or alkaline phosphatase (250 U/ml). On the other hand, when fragmented membranes from inside-out vesicles were incubated with gamma-32 P-ATP and 1 microM free Ca2+ under above conditions, only two high-molecular weight polypeptides (235 and 320 kDa) were labelled with 32P. The results suggest that ATP-mediated phosphorylation of Ca(2+)-dependent K+ channels leads to a high-conductance state. PMID- 1303590 TI - Effects of simultaneous denervation and tenotomy on the ultrastructure of a rat slow twitch muscle. AB - Simultaneous denervation and tenotomy causes atrophy of rat slow twitch soleus muscle. Apparently, the alterations are similar to those seen in denervated or tenotomized slow muscle. However, the extent of disorganization of myofibrils appears lower than that expected after a moderate period of time in only denervated or tenotomized muscle. This study indicates that after an initial proliferation of lysosomes, alterations of sarcotubular system and mitochondria proceed. Nevertheless, 45 days after denervation and tenotomy many mitochondria have a normal aspect. PMID- 1303591 TI - [How to evaluate prospectively cutaneous sclerosis in systemic scleroderma?]. PMID- 1303592 TI - [Value (and limitations) of the RAST fx5 in pediatric allergological practice]. AB - RAST f x 5 (CAP-system, Pharmacia), an in vitro assay testing a mixture of 6 food antigens, was systematically applied to 400 children and adolescents with respiratory pathologies possibly of allergic origin. The clinical aspects of the 293 test-negative patients were compared with those of the 107 positive cases. Furthermore, 84 positive sera were also evaluated against each of the 6 antigens regrouped in the f x 5. In this population with allergic respiratory diseases, the most frequently positive tests reacted with antigens of plant origins: wheat, peanut and soybean. From an economic point of view, first-line use of f x 5 markedly reduced the cost of a systematic study of food allergens, whose clinical justification remains to be demonstrated. PMID- 1303593 TI - [Objective evaluation of sclerodermic skin using the slip-test. Results and validation with 30 patients and 60 controls]. AB - The slip test is a non-invasive way to objectively evaluate the extent of scleroderma by measuring the "slipping" of the skin over an underlying bone. The results obtained in 30 scleroderma patients and 60 controls (178 tests due to multiple measurements) were analyzed to determine which test sites show a significant difference between patients and controls (Student's t-test) and which sites are the most discriminating for the diagnosis of the disease (multivariate analysis). Patient values were clearly distinct from those of controls. The best sites (defined by p < 0.05) were: the mandible, the second and first phalanges of the middle finger, the hands, the forearms, the epicondyles, the sternum, the iliac crests, the patellae, the tibias (the upper and lower fourths) and the feet; in all, 23 sites to which can be added the opening of the mouth (measurement of the maximal interlabial distance), which proved to be a reliable parameter. Multiple regression analysis yielded an equation that identified patients with scleroderma based on 4 variables (right forearm, right iliac crest, sternum and right rib). The slip test is thus the first reproducible quantitative test able to confirm and quantify clinical impressions in scleroderma. It is entirely able to objectively monitor the evolution of the disease under treatment. Nevertheless, complementary studies are needed to verify whether the slip test, which can be performed in 20 minutes during an office visit, can be used advantageously in the routine clinical evaluation of scleroderma. PMID- 1303594 TI - [Recurrence of Guillain-Barre syndrome]. AB - Fifteen of the 238 patients (6.3%) who recovered from an initial episode of Guillain-Barre syndrome had one or several acute relapses. Usually, there was only one relapse. The durations of the plateau and recovery phases of the relapses were longer than those of the initial episodes. The protein level in the cerebrospinal fluid was higher during relapses (1.37 +/- 1.30 milligrams) than during the initial episode (0.87 +/- 0.44 milligrams). The intensity of the symptoms during relapses was comparable to that of the initial episodes, but the occurrence of these relapses aggravated functional sequelae. Comparison of relapsing patients with those who experienced monophasic Guillain-Barre syndromes and were treated in the same unit revealed no element predictive of relapses. PMID- 1303596 TI - [IgA deficiency]. PMID- 1303595 TI - [Long-term survival and prognostic factors in stage II-III multiple myeloma treated with conventional chemotherapy]. AB - In this retrospective study, survival and prognostic factors were analysed in 65 patients with stage II-III multiple myeloma with osteolytic lesions. Multiple myeloma was diagnosed from 1976 to 1984, and patients were treated with conventional chemotherapy. The response rate to initial chemotherapy was 46%. The median survival time was 31 months. The 10-year survival rate was 10%. Four variables were individually prognostic: response to initial chemotherapy, bone marrow plasma cell percentage, the Durie and Salmon staging system, a biological staging system derived from Durie and Salmon's biological criteria regardless of bone lesions. In the multivariate analysis, only two prognostic variables were retained, namely the response to chemotherapy and the biological staging system. No prognostic value was observed for the extent of osteolytic lesions. This study suggests that, in conventionally treated multiple myeloma, long-term survival has improved compared with the previous decade. It also indicates that the extent of osteolytic lesions has little value for the definition of high-risk myeloma. PMID- 1303597 TI - [Biology of interleukin-6. Role in lymphoplasmacytic hemopathies]. PMID- 1303598 TI - [Cerebrovascular complications disclosing Conn's adenoma]. PMID- 1303599 TI - [Association of glomerular nephropathy with IgA deposits and relapsing polychondritis]. PMID- 1303600 TI - [Pneumopathy induced by amiodarone. Radiological data]. AB - Amiodarone is a drug used to treat refractory tachyarrhythmias. Unfortunately, amiodarone causes numerous side effects, among them the most serious is a pulmonary toxicity. Conventional radiographic findings are non specific and may be observed in various diseases, however. Early recognition of pulmonary toxicity is important, since prompt discontinuation of the drug, and institution of corticosteroids should result in resolution of toxicity. PMID- 1303601 TI - [Wegener's disease: value of thoracic computed tomography. Apropos of a case and review of the literature]. AB - The authors demonstrate the value of thoracic HR-CT in a case of Wegener's granulomatosis with a typical presentation. This uncommon disease, often has a pseudo-infectious or pseudo-neoplastic appearance and the diagnosis can be difficult as indicated by a review of the literature. PMID- 1303602 TI - [Primary mediastinal myxoid liposarcoma. Apropos of a case]. AB - Liposarcoma is an uncommon mediastinal tumor provides limited CT histologic date. The prognosis depends on the histological grade and surgical possibilities. The authors report a case of mediastinal liposarcoma and discuss the correlation between imaging findings, outcome and histological status. PMID- 1303603 TI - [Neurinomas of the trigeminal nerve in neurofibromatosis. Apropos of two cases and review of the literature]. AB - We report two cases of trigeminal neuroma in patients with Von Recklinghausen neurofibromatosis (NF1). Despite the high frequency of intracranial neuroma in neurofibromatosis, the localization on the fifth cranial nerve is an uncommon findings. In our two cases, neuromas were asymptomatic clinically and electrophysiologically, but computed tomography showed a small nodular lesion in the cerebellopontine cistern, independent of the seventh and eight nerve and which can only correspond to the fifth nerve. MR imaging very clearly demonstrates intracranial neuromas of all cranial nerves. PMID- 1303604 TI - [Sirenomelia: morphological and radiological study of a new case]. PMID- 1303605 TI - [Blind ureter associated with a dysplastic kidney and ureterocele. Apropos of a case and review of the literature]. AB - The association of a blind ureter with dysplastic kidney and ureterocele is known in children but are in adults. This paper presents one case, and provides simple diagnostic clues which help to recognize the malformation. PMID- 1303606 TI - [Aneurysm of the superior mesenteric vein]. AB - Aneurysms originating in the superior mesenteric vein are extremely rare: 4 cases have been reported in the international literature. The authors describe a case of a female patient admitted to hospital for vague abdominal pain. The CT findings revealed a cyst-like neoformation. By means of angiography it was then identified as a dilatation of the superior mesenteric vein. The causes of such dilatations are not altogether clear. Current interpretations refer to possible congenital and acquired factors, as well as trauma. The accompanying symptoms are abdominal pain, icterus, gastrointestinal haemorrhage or portal hypertension, but occasionally patients may present no symptoms whatsoever. PMID- 1303607 TI - [Computed tomography of gastric lymphoma: study technique and diagnosis. Apropos of three cases]. PMID- 1303608 TI - [Ectatic tumoral thrombosis of the superior vena cava revealing thyroid cancer]. AB - Microscopic angio-invasion by carcinoma of the thyroid is known. Extension into the great veins is much more uncommon. Most of the cases which have been previously described were discovered on post-mortem examination. We report the case of a 55 year-old woman who was found to have an asymptomatic small cervical goiter 6 years ago; during the last 12 months she developed superior vena cave (SVC) syndrome radiological investigation (angiography, CT scan) and surgical exploration showed a carcinoma of the thyroid with intraluminal extension of the tumor leading to thrombosis and ectasia of the SVC. Surgery was performed with resection of the whole thyroid, the SVC and the innominate veins. A double prosthetic venous by pass was then inserted between the innominate veins and right atrium. Five years after resection, the patient has no recurrence or metastasis and no clinical symptom of SVC syndrome. To our knowledge, this is only the third reported case successfully treated by surgery. PMID- 1303609 TI - [Secondary bronchogenic pulmonary hydatidosis]. AB - Secondary bronchogenic hydatid disease is a rare and little known complication of primary hydatid cyst of the lung, which is even refuted by some authors. We report 7 cases of secondary bronchogenic hydatid after surgical cure of a hydatid cyst which had ruptured into the bronchi, while the last case concerned a young girl who was treated by corticosteroids for rheumatoid arthritis and who developed secondary bronchogenic hydatid from a cyst rupturing into the bronchi in the absence of surgery. Hydatid dissemination was ipsilateral to the primary cyst in 5 cases, contralateral in one case and bilateral in one case. Five patients underwent radical surgery. The patient with bilateral dissemination was operated on one side and a large number of residual cysts were eliminated by vomica, as for the last patient; these two patients are still under surveillance. The operation and general anaesthesia played a predisposing role in the pathogenesis of this complication and inhibition of immune mechanisms could also play a role. Prevention is necessary when treating a hydatid cyst of the lung which has ruptured into the bronchi. Treatment is surgical, bearing in mind that a large number of secondary cysts can be eliminated by vomica or may involute spontaneously. PMID- 1303610 TI - [Primary intrahepatic lithiasis]. AB - Isolated intrahepatic lithiasis is a very rare condition in western countries; the reported case has to be added to the 29 cases described to date in the literature. The pathogenesis of this disease is unknown; physical and chemical bile alterations favouring lithogenesis is the most reliable hypothesis. In this case the Roux-en-Y hepaticojejunostomy with cutaneous stoma allowed us to perform periodic cleaning of intrahepatic bile ducts until complete elimination of all stones. PMID- 1303611 TI - [Ileovaginal fistula after ileo-anal anastomosis. Recovery by transposition of the gracilis muscle. Good anatomical and functional result]. AB - One women developed a pouch-vaginal fistula after reconstructive proctocolectomy for ulcerative colitis. This study describes the risk factors which predispose to the development of this rare complication, as well as the various treatment options available. A diverting ileostomy was maintained and gracilis muscle interposition flap was used to treat the patient. An excellent result was achieved. This procedure can be useful in this rare but distressing complication. PMID- 1303612 TI - A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer. AB - To decrease the toxicity of hepatic arterial fluorodeoxyuridine (FUDR) administered through an Infusaid pump (Shiley Infusaid, Inc., Norwood, MA), 50 patients with liver metastases from colorectal cancer were selected randomly to receive FUDR, 0.3 mg/kg/d, for 14 of 28 days, with or without a total dose of 20 mg of hepatic arterial dexamethasone for 14 of 28 days. Patients were stratified according to the percentage of liver involvement by tumor and the perfusion pattern on macroaggrated albumin perfusion scan (MAA) scan. There was a trend toward decreased frequency of bilirubin levels in the group receiving dexamethasone plus FUDR versus the group receiving FUDR alone (9% and 30%, respectively, had a 200% or greater increase from baseline; P = 0.07). Patients in the group treated with dexamethasone and FUDR received higher doses of FUDR in the second, third, fifth, and sixth months than those receiving FUDR alone; however, this was statistically significant only in the fifth month (percentages of planned dose received: 42% and 19%, respectively; P = 0.05), and there was no overall difference for the total 6-month period. The complete and partial response rates were increased in patients receiving dexamethasone and FUDR versus FUDR alone (8% and 63% versus 4% and 36%, respectively; P = 0.03), and there was a trend toward increased survival with the addition of dexamethasone (median, 23 months and 15 months, respectively; P = 0.06). In conclusion, the use of hepatic arterial dexamethasone is associated with an increased response rate and a trend toward increased survival and decreased bilirubin levels. Therefore, the authors recommend additional investigation of the use of dexamethasone with chemotherapy to treat hepatic metastases. PMID- 1303613 TI - Second-look laparotomy and salvage therapy: a research modality only? AB - Two hundred twelve patients who underwent second-look laparotomy as part of their treatment for epithelial ovarian cancer were evaluated. Factors associated with positive second looks were initial stage, tumor grade, age, and residual disease (P less than 0.05). One factor not of significance was whether adjuvant therapy was platinum based. Initial stage only was associated with recurrence after a negative second look (P less than 0.001). When controlled for volume of disease no difference in survival between various salvage therapies could be demonstrated. Survival between patients with recurrence after negative second look and patients with microscopic residual disease was similar even though the former group was not treated until recurrence (P = 0.75). Second-look laparotomy does not improve survival with currently existing salvage modalities and should primarily be confined to those patients willing to participate in research protocols evaluating new second-line therapy. PMID- 1303614 TI - Myocardial contusion after a professional boxing match. PMID- 1303615 TI - Nasal reconstruction. PMID- 1303616 TI - Locked-in syndrome. PMID- 1303617 TI - The shortage of organs for transplantation. PMID- 1303618 TI - Viability of skin biopsies stored at -70 degrees C. PMID- 1303619 TI - Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance. AB - Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. In addition to this triad, other variable features of dermatopathia pigmentosa reticularis have been described, including adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis. Only 10 cases have been described in the world literature to date, and no clear inheritance pattern has been demonstrated. We present a patient with the classic features of the dermatopathia pigmentosa reticularis triad, along with adermatoglyphia, hypohidrosis, and punctate hyperkeratosis of the palms and soles. A family pedigree demonstrates the autosomal dominant inheritance of dermatopathia pigmentosa reticularis. PMID- 1303620 TI - Trichotillomania treated with clomipramine and a topical steroid. PMID- 1303621 TI - Rheumatologists as an endangered species: a proposal for change. PMID- 1303622 TI - Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. AB - An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae. PMID- 1303623 TI - Evaluation of tissue oximetry in perioperative monitoring of colorectal surgery. AB - Twenty patients undergoing elective colorectal surgery were studied during and after operation by means of tissue oximetry measuring the subcutaneous partial pressure of oxygen (PscO2) and by gastric intramural pH measurement. Mean(s.d.) PscO2 recorded 24 h after surgery was significantly lower than the peroperative value: 14(10) versus 24(14) mmHg, P less than 0.02. The postoperative PscO2 was also significantly lower than that measured in a control group of ten healthy volunteers: 14(10) versus 34(18) mmHg, P less than 0.001. The peroperative PscO2 of the patients who developed a postoperative complication was significantly lower than that of those who had an uneventful postoperative clinical outcome: 16(9) versus 32(14) mmHg, P less than 0.02. The peroperative PscO2 of the patient group with complications was also significantly lower than that of the control group: 16(9) versus 34(18) mmHg, P less than 0.02. The peroperative PscO2 of the group of patients without complications was almost identical to that of the control group. During operation only one patient developed gastric intramural acidosis. Perioperative oxygen debt and the response of subcutaneous tissue oxygen tension to oxygen breathing seemed to correlate better with clinical outcome than gastric wall pH values and the conventional parameters of tissue perfusion. PMID- 1303624 TI - Reversible dilated cardiomyopathy due to thyrotoxicosis. PMID- 1303625 TI - Malpractice lawsuits and paranoia. PMID- 1303626 TI - Concerning the possibility of a nut... PMID- 1303627 TI - Output factors for blocked fields. AB - This study investigates the output from blocked treatment fields with 6 MV and 18 MV photons. Square fields, defined by collimators, were blocked down to smaller symmetrical square, rectangular and asymmetrical rectangular fields using blocks on a tray beneath the collimators. Up to 7.5% difference was found between the output measured for the blocked field and the output calculated using a collimator output factor for the surface field size. A method is described by which output factors for the blocked fields can be measured and used in practice. Three methods of approximating these output factors are also presented. PMID- 1303628 TI - Abdominal pain: parietal or visceral? PMID- 1303629 TI - Birth prevalence study of the Apert syndrome. AB - Estimates of the Apert syndrome birth prevalence and the mutation rate are reported for Washington State, Nebraska, Denmark, Italy, Spain, Atlanta, and Northern California. Data were pooled to increase the number of Apert births (n = 57) and produce a more stable birth prevalence estimate. Birth prevalence of the Apert syndrome was calculated to be approximately 15.5/1,000,000 births, which is twice the rate determined in earlier studies. The major reason appears to be incomplete ascertainment in the earlier studies. The similarity of the point estimates and the narrow bounds of the confidence limits in the present study suggest that the birth prevalence of the Apert syndrome over different populations is fairly uniform. The mutation rate was calculated to be 7.8 x 10( 6) per gene per generation. Apert syndrome accounts for about 4.5% of all cases of craniosynostosis. The mortality rate appears to be increased compared to that experienced in the general population; however, further study of the problem is necessary. PMID- 1303630 TI - Ketorolac trometamol for postoperative analgesia after orthopaedic surgery. AB - We have compared the postoperative morphine requirements and analgesic efficacy of four doses of i.m. ketorolac 30 mg administered 6-hourly with placebo in a double-blind study of patients undergoing major or minor orthopaedic surgery. During the 24-h postoperative study period which began at the end of surgery, patients were prescribed i.m. morphine 10 mg as required 2-hourly and assessments were made of pain at 4 and 24 h. After major surgery, the median morphine consumption over 24 h was 10 mg in patients who received ketorolac, compared with 30 mg in those who received placebo (P = 0.008). Visual analogue pain scores and verbal pain assessments were better than placebo at 4 h (P = 0.028 and P = 0.008, respectively), but were not statistically different between the groups at 24 h. Overall assessment of pain was similar in both groups who had undergone major surgery. In the minor surgery groups, median morphine consumption was 0 mg in patients who received ketorolac, compared with 10 mg in those given placebo (ns). Visual analogue pain scores at 24 h after surgery were significantly less in patients who had received ketorolac compared with placebo (P = 0.046) and the overall assessment of pain relief was better in the ketorolac group (P = 0.0007). Mandatory administration of ketorolac appeared to be of benefit in both major and minor orthopaedic surgery, although the principal effects were reduction in requirement for supplementary morphine for major surgery and better overall analgesia for minor surgery. PMID- 1303631 TI - Human immunodeficiency virus type 1-infected monocytic cells can destroy human neural cells after cell-to-cell adhesion. AB - Primary cultures of human embryonic neurons and astrocytes have been used to test the interactions between neural cells and either human immunodeficiency virus type 1 (HIV-1) or HIV-1-infected monocytes. After direct infection with HIV-1, neither morphological alteration of neurons and astrocytes nor signs of viral replication were observed. Similarly, cultured human neurons and astrocytes were resistant to incubation with the supernatant of HIV-1-infected U937 cells, a human monoblastoid cell line. In contrast, HIV-1-infected U937 monocytic cells adhered to neural cells and induced large plaques of necrosis surrounding them. This cytopathic effect began at the time of viral replication (day 16 after infection). Its intensity depended on that of viral replication, and its range was identical to the region of diffusion of viral antigens, as judged by immunocytochemistry. The cytopathic effect was not dependent on the release of free radicals. It could not be induced by cytokines or cytokine-stimulated U937 cells. It is likely that this cytopathic effect depends on the release of viral antigens either within the site of adherence itself or within close range of the astrocyte membrane. PMID- 1303632 TI - The response of 99Tcm-methylene diphosphonate and 99Tcm-hexametazime-labelled neutrophils to intra-articular steroid injection in rheumatoid arthritis. AB - The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA. PMID- 1303634 TI - Internal medicine and the training of international medical graduates: a time for open discussion and new approaches. AB - The number of foreign national medical graduates entering internal medicine residency training programs in the United States has doubled since 1986. A rigorous, standardized preresidency evaluation of the basic clinical skills and language abilities of international medical graduates should be implemented. Those found to have significant deficits should undertake a preparatory curriculum designed to meet special educational needs before entry into the formal training program. A relevant curriculum might include formal lectures, reading assignments, physical diagnosis sessions, language classes, patient encounter sessions, and a tutorial on U.S medical culture that includes medical ethics and the basics of the our health care system. All or only some of these may be required for any given individual. The Educational Commission for Foreign Medical Graduates (ECFMG) could provide many of the methods needed for an evaluation program and work collaboratively with program directors. This new approach to training of international medical graduates will require an evaluation system to to measure its effectiveness. Important questions about the funding of graduate medical education for international medical graduates must also be addressed. PMID- 1303633 TI - Pharmacokinetics of ethylene in man; body burden with ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental ethylene. AB - The inhalation pharmacokinetics and the endogenous production of ethylene has been determined in healthy volunteers with respect to the formation of the carcinogen ethylene oxide. Ethylene showed a low degree of accumulation in the body determined in six subjects, the thermodynamic partition coefficient "body/air" being 0.53 +/- 0.23 (mean +/- SD) and the accumulation factor "body/air" at steady-state being 0.33 +/- 0.13 (mean +/- SD). The rate of metabolism was directly proportional to the exposure concentration. Only 2% of ethylene inhaled was metabolized to ethylene oxide, whereas 98% of ethylene was exhaled unchanged. The rate of the endogenous production of ethylene was 32 +/- 12 nmol/h (mean +/- SD), as calculated from exhalation data from 14 subjects. The resulting body burden was 0.44 +/- 0.19 nmol/kg (mean +/- SD). By analyzing published data on ethylene oxide in man its half-life was estimated to be 42 min. Using the pharmacokinetic parameters of ethylene and ethylene oxide, the body burden of ethylene oxide due to the sum of the exposure to environmental ethylene of about 15 ppb and to endogenous ethylene exposure of 0.44 nmol/kg was predicted to be 0.25 nmol/kg. In the blood of five non-smokers and one smoker the hemoglobin adduct resulting from the reaction of ethylene oxide with the N terminal valine, N-(2-hydroxyethyl)valine, was quantified by gas chromatography/mass spectrometry. The value of 20 +/- 5 pmol/g Hb (mean +/- SD) found in the non-smokers corroborated the steady-state level of 18 +/- 3 pmol/g Hb (mean +/- SD) calculated from the pharmacokinetic approach. PMID- 1303635 TI - Detection and management of lipid disorders in diabetic patients. A commentary for clinicians. PMID- 1303636 TI - Regulated medical waste: is any of it infectious? PMID- 1303637 TI - Recurrent parotitis. AB - Recurrent parotitis in children is a well described but rare condition of unknown cause. The clinical features of 11 children with recurrent parotitis are described. PMID- 1303639 TI - A randomized trial of psychosocial support during high-risk pregnancies. The Latin American Network for Perinatal and Reproductive Research. AB - BACKGROUND: It is often suggested that psychological and social support and health education for women at high risk for delivering a low-birth-weight infant can improve the outcomes of pregnancy, but the evidence is inconclusive. We undertook this prospective trial to evaluate a program of home visits designed to provide psychosocial support during pregnancy. METHODS: At four centers in Latin America, 2235 women at higher-than-average risk for delivering a low-birth-weight infant were recruited before the 20th week of pregnancy. The women were randomly assigned either to an intervention group (n = 1115) that received four to six home visits from a nurse or social worker in addition to routine prenatal care or to a control group (n = 1120) that received only routine prenatal care (with a mean of eight prenatal visits). The principal measures of outcome were low birth weight (< 2500 g), preterm delivery (< 37 weeks of gestation), and specified categories of maternal and neonatal morbidity. RESULTS: The women who received the home visits as well as routine prenatal care had outcomes that differed little from those of the women who received only routine care. The risks of low birth weight (odds ratio for the intervention group as compared with the control group, 0.93; 95 percent confidence interval, 0.68 to 1.28), preterm delivery (odds ratio, 0.88; 95 percent confidence interval, 0.67 to 1.16), and intrauterine growth retardation (odds ratio, 1.08; 95 percent confidence interval, 0.83 to 1.40) were similar in the two groups. There was no evidence that the intervention had any significant effect on the type of delivery, the length of hospital stay, perinatal mortality, or neonatal morbidity in the first 40 days. There was no protective effect of the psychosocial-support program even among the mothers at highest risk. CONCLUSIONS: Interventions designed to provide psychosocial support and health education during high-risk pregnancies are unlikely to improve maternal health or to reduce the incidence of low birth weight among infants. PMID- 1303638 TI - Blood lead level in children living close to a smelter area: 10 years later. AB - A survey conducted at the end of the summer of 1989 in Rouyn-Noranda showed that children living near the smelter had blood lead levels between 2.3 and 26.9 mg/dl. A comparison with a similar survey done in the same area in 1979 shows that there are fewer children today with a blood lead level higher than 20 mg/dl, that is 7 versus 18, ten years ago. The soil lead level of the area where these children live was elevated but comparable to that of 10 years ago, even if the smelter atmospheric lead emissions show an important decrease, as is the case for atmospheric lead contamination by leaded gas. Shall we reconsider our criteria for remedial action on the soil? PMID- 1303640 TI - Validation of ambulatory monitors in special populations. PMID- 1303641 TI - Intestinal parasite control in an institution for developmentally handicapped adults. AB - An intestinal parasite eradication program consisting of antiparasitic drug treatment and hygiene measures was conducted at an Ontario residential facility for developmentally handicapped adults from October, 1989 to August, 1990. The prevalence of intestinal parasites in general was initially over 90% while that of pathogenic species was 59%. Six months later, overall prevalence and that of pathogenic species were reduced to 32.9% and 11%. In one subgroup, the reduction in the prevalence of pathogenic parasites was sustained for at least one year. However, the prevalence of non-pathogenic species was similar to the baseline level. Simultaneous treatment and application of hygiene measures appeared to be effective in reducing pathogenic intestinal parasites. PMID- 1303642 TI - Low anion gap resulting from unexplained exposure to bromide in a patient with renal amyloidosis. AB - A patient with nephrotic syndrome secondary to renal amyloidosis was consistently observed to have serum anion gap levels as low as -1 mEq/L and averaging approximately 2 mEq/L. Neither multiple myeloma nor extreme hypertriglyceridemia was present, and the patient's serum albumin concentrations were not low enough to depress the anion gap to this degree. An increased serum bromide level (below the range expected to produce clinical toxicity) was the apparent cause of the low anion gap. The patient's parents, who live in the same apartment, also manifested low anion gaps and inexplicably elevated serum bromide levels. Despite detailed investigation, no environmental or pharmacologic source of bromide was uncovered. Although the source of the bromide in the present instance remains elusive, this report illustrates the necessity to measure serum bromide when a low anion gap cannot be explained by other factors, even when there is no history to suggest bromide exposure. PMID- 1303643 TI - Diet and breast cancer. AB - Studies show no correlation between dietary fat and breast cancer. It is time to move on. PMID- 1303644 TI - Falsely negative urine drug assay results due to filtration. PMID- 1303646 TI - Confounding in epidemiological studies. PMID- 1303645 TI - 'Orthodontic relapse'. PMID- 1303647 TI - Technique for laparoscopic appendicectomy. PMID- 1303648 TI - Lipomas of anterior neck simulating nodules. PMID- 1303649 TI - Screening for neuroblastoma in the north of England. AB - OBJECTIVE: To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN: Prospective study of mass screening in four clearly defined geographical areas. SETTING: Four health districts of the Northern region of England. SUBJECTS: 20,829 babies aged 6 months, 92% of target population. INTERVENTIONS: Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME MEASURES: Derivation of reference range. Identification of babies with homovanillic or vanillylmandelic acid > 3 SD above the mean (positive cases). Investigation of positive cases for evidence of neuroblastoma. RESULTS: The upper limit of normal (3 SD above the mean) for vanillylmandelic acid was 15 mumol/mmol creatinine and for homovanillic acid 24 mumol/mmol creatinine. Of the 20,829 babies screened, 2537 (12.2%) required a second sample to be taken because the first sample was inadequate. Of these, 527 (2.5%) provided a liquid urine specimen and 10 (0.04%) had positive results for neuroblastoma. Two of them had neuroblastoma (true positives) and eight did not (false positives). A further three children from the cohort were subsequently found to have neuroblastoma; they had raised homovanillic acid or vanillylmandelic acid values, or both, but screened negative at 6 months. CONCLUSIONS: Screening for neuroblastoma is possible in the health care system of the United Kingdom. Evaluation of the efficacy of screening in reducing the mortality from neuroblastoma requires a controlled trial. PMID- 1303651 TI - Letting vegetative patients die. PMID- 1303650 TI - Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies. AB - Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity. PMID- 1303653 TI - Spirituality, healing and medicine. PMID- 1303652 TI - Stroke and the carer. PMID- 1303654 TI - Side effects of influenza immunization. PMID- 1303655 TI - Decreasing quality of semen. PMID- 1303656 TI - Outcome of breech delivery at term. PMID- 1303657 TI - Needs and demands for ophthalmology services. PMID- 1303658 TI - HIV disease and pregnancy. PMID- 1303659 TI - Identification of pit bull terriers. PMID- 1303660 TI - Plasminogen activator inhibitor-1 levels determine the profibrinolytic response in disseminated intravascular coagulation. PMID- 1303661 TI - Selection of optimal lipid sources in enteral and parenteral nutrition. AB - The manipulation of dietary fat intake can affect the response to disease, injury, and infection. These effects include enhancement or inhibition of immune function, altered susceptibility to cardiovascular disease, promotion or maintenance of gut integrity, and prevention of total parenteral nutrition induced hepatic dysfunction. These effects may occur as a result of changes in the fatty acid composition of biomembranes or changes in concentrations of lipid moieties such as prostaglandins or leukotrienes. Those fats that have been shown to affect physiologic function include long-chain, medium-chain, and short-chain fatty acids and omega-3 and omega-6 fatty acids. Currently available enteral and parenteral products used for nutrition support contain widely varied amounts of these different fatty acids. Therefore, the selection of the most appropriate product or nutrition support regimen for an individual patient requires an understanding of the metabolism of these different fat substrates, their therapeutic indications, and the contraindications and controversies that surround their use. This article reviews these issues and also focuses on several alternate lipid sources such as short-chain fatty acids, medium-chain fatty acids, omega-3 fatty acids, and blended and structured lipids. PMID- 1303662 TI - Food and nutrition guidelines. PMID- 1303663 TI - [Effect of anisodamine on cochlear blood flow in living guinea pigs]. AB - Anisodamine is commonly used in clinic as vasodilator. In the present study, the effects of anisodamine on cochlear blood flow were investigated in living guinea pigs using intravital microscopic techniques. The results showed that intravenous infusion of anisodamine (10mg/kg, 5mg/kg, 2 mg/kg) produced a dose dependent reduction in blood pressure. Large dose (10mg/kg) caused significant decrease in blood flow rate to 68.7 +/- 7.4% of the control value with no significant change in vessel diameter. On the other hand, medium and small doses (5mg/kg, 2mg/kg), which produced relatively smaller reduction in blood pressure caused no significant alternation in blood flow rate and vessel diameter. Also, when intramuscular, infusion of anisodamine (2mg/kg) was used no significant difference in blood flow rate, vessel diameter as well as blood pressure were found. The results indicated that increase in cochlear blood supply can not be induced by anisodamine in normal guinea pigs. PMID- 1303664 TI - [Effect of impulse noise exposure on the endocochlear potentials]. AB - Effects of impulse noise exposure (25 impulses, peak level 165 dB SPL) on endocochlear potentials (EP) and CAP threshold were investigated in guinea pigs. Eight hours after exposure, EP recorded from the second turn of the cochlea was very low (19.0 +/- 1.7 mV) and the negative EP resulted from prolonged anoxia was markedly diminished (-EPmax = -6.4 +/- 1.3 mV). The return rate of EP after reventilation was also reduced. The positive EP returned to normal values 7 days after exposure but the negative EP and the CAP threshold did not. The results suggest that the stria vascularis was also damaged together with the organ of Corti, the degree of damage seemed to be heavier in the latter if only complete recovery of positive EP is taken into consideration. The stria vascularis was also not completely restored when examining the return rate of EP after reventilation. Mechanisms underlying the changes in EP and hearing sensitivity after noise exposure are discussed. PMID- 1303665 TI - [Compensation of the inner ear exposed to stabile noises of different intensities]. AB - The dynamic changes of AP to click stimuli. the values of the static EP and the cochlear ultrastructures of the albino guinea pigs after exposure to stabile noise of three intensities (115dBA, 125dBA, 130dBA) for 4 hours were observed. At 115dBA, EP did not change; the threshold of AP was 46 +/- 6dBHL, which returned to normal 3 days after exposure. At 125dBA, EP increased to 91.6 +/- 6.9mv, and took 3 days to recover; AP was 64 +/- 3dBHL, and recovered completely in 14 days. At 130dBA, EP decreased to 68.7 +/- 19.3 mv, spending 7 days to resume; AP was 68.5 +/- 4.7dBHL, not returned to control level during 14 days. The cochlear impairment aggravated with intensified noise level, and did not improve as EP and AP recovered. At 130dBA, there were several minor holes and fractures in the reticular lamina. These results indicate that the different intensities of noises cause different conditions of noise-induced inner ear injury. The inner ear has a peculiar compensation mechanism to resume stability. PMID- 1303666 TI - [Distorsion-products otoacoustic emissions in acoustic neuroma]. AB - Eight cases with surgically confirmed 1.5-3.5 cm acoustic neuromas were tested through measuring distorsion-products otoacoustic emissions (DPO), which objectively reflects the cochlear status. Only one frequency (Ft) corresponding to behavior threshold highest dB HL is selected as a frequency site of DPO. The DPO is collected at a level of 75 dB SPL with equilevel of stimuli f1 and f2 and proper frequency separation (f2/f1 = 1.2). The frequencies of stimuli f1 and f2 can be calculated through the formula Ft=2f1-f2. Six cases with less than 3.0 cm neuromas had normal amplitude of DPO. Decreased amplitude of DPO is found in two cases suffered from 3.0-3.5 cm neuromas. The discrepancy between behavior threshold and amplitude of DPO can be an important indication for distinguishing early retrocochlear lesions, for instance, acoustic neuroma. PMID- 1303667 TI - [Transtemporal supralabyrinthine approach]. AB - Transtemporal supralabyrinthine approach is a modified middle cranial fossa approach. It offers all the advantages of a middle cranial fossa procedure and avoids its disadvantages, mainly the extensive temporal lobe retraction and frightening complications. The principle of the approach is to gain sufficient access toward the internal auditory canal by removing bone from the roof of the petrous pyramid rather than by elevating the middle fossa dura away from it. Fifteen patients underwent this approach for decompression of paralysed facial nerve resulted from temporal bone fracture, Bell's palsy and herpes zoster oticus; for removal of facial neuromas and primary cholesteatomas in temporal bone and for sectioning of great superficial petrous nerve. Preliminary study showed good results. PMID- 1303668 TI - [Detection of G-T mutations at codon 12 of c-Ha-ras oncogenes in squamous cell carcinomas of the sinus maxillaris]. AB - DNA extracted from paraffin-embedded minor carcinoma tissues of the sinus maxillaris, G-T mutations at codon 12 of c-Ha-ras oncogenes were detected with polymerase chain reaction and mutation-specific oligonucleotide probe hybridization, the mutations were identified in 5 out of 20 squamous cell carcinomas of the sinus maxillaris. This result indicated that c-Ha-ras oncogene is one of the genes associated with the development and progression of the squamous cell carcinomas of the sinus maxillaris, and G-T mutation may lead to activation of the c-Ha-ras oncogene. PMID- 1303669 TI - [Functional endoscopic sinus surgery]. AB - Eighty-two cases of functional endoscopic sinus surgery were analyzed. It include 62 males and 20 females; the oldest was 72 years of age and the youngest eight years of age. A hard endoscope with a diameter of 4mm and the CCD micro videorecorder produced by Circon and Olympus Company were used. Operations were done under general anesthesia in all cases. Twenty-three cases (28.1%) recovered in one stage and recovery was delayed in 28 cases (34.2%); late inflammation occurred in 23 cases (28.1%); 8 cases failed (9.8%). The cure rate was 62.2%. Two cases (2.4%) had operative complications namely injury to the lamina papyracea and anterior ethmoidal artery, all recovered uneventfully. PMID- 1303670 TI - [Chromosomal analysis of human squamous cell carcinoma of the larynx]. AB - Twenty cases of human squamous cell carcinomas of larynx were processed with an improved direct chromosome preparations. Metaphases were obtained from 5 cases and detailed G-banding analyses were completed in 3 cases. In addition, a cell line of squamous cell carcinomas of larynx (HEP-2) was analyzed with high resolution banding technique. Three generations were cytogenetically analyzed (365, 375, 395). DM, which indicate gene amplification was found in case 4 and the cell line. 6q- and i (8q) appeared in both primary tumors and the cell line, and thus could be considered as characteristic changes in human squamous cell carcinomas of larynx. PMID- 1303671 TI - [Transforming growth factor alpha and head and neck neoplasms]. PMID- 1303672 TI - [Anemia and iron therapy]. PMID- 1303673 TI - [Effect of the father-daughter relationship on the morphological development of the mammary glands]. AB - The puberal development of the mammary glands is the result of a final increase of serum estradiol. Having observed that the relationship with the father can affect the concentration of estradiol in the serum, the authors studied the relationship between the intensity of that interaction and the morphological development of the breasts, a standing witness in a woman's body of the concentration of estradiol in the serum during the pubertal stage. The study had two parts: 1) The review of the clinical histories of 145 nulliparous women between 18 and 25 years of age. 57.3% lived with their fathers, while 42.6% had no father, either because of death or separation. The difference between both groups in breast size as well as in the width of the areola was significant. There was also a significant difference depending on whether the separation occurred before or after the girl was 9 years old. 2) The administration of a questionnaire to 90 nulliparous women between the ages of 18 and 25, to establish the intensity of the father/daughter relationship. The results showed significant differences between the intensity of the father/daughter relationship, breast size and width of the areola. There was no significant correlation between the intensity of the relationship and the pigmentation of the areola in either of the two phases. PMID- 1303674 TI - [CD10(CALLA)-negative acute lymphoblastic leukemia. A group with a bad prognosis]. AB - The results of 188 patients with acute lymphoblastic leukemia, studied between 1985 and 1990, showed that 8 cases were CD10 negative, Dr, and CD19 positive. These findings indicate cell dedifferentiation and poor prognosis. The patients age ranged from 2 to 30 years, with a mean of 11 years. The male/female ratio was 5/3. Lymph node enlargement and splenomegaly were found in the 8 patients. With the exception of one patient in whom leucopenia was present, the white cell counts were always higher than 30,000/dl. The karyotype was studied in four cases, and all of them were hyperdiploid. This is the first report in Venezuela of cases with acute lymphoblastic leukemia - CD 10 negative. PMID- 1303675 TI - [Renal osteodystrophy in Maracaibo]. AB - In the present work we report the bone histologies obtained from the iliac crest of 49 patients on chronic hemodialysis in Maracaibo. All of them were dialyzed thrice weekly with untreated tap water containing high aluminum (Al) levels. Their mean blood Al levels were found to be higher than 100 micrograms/L. Histomorphometry was used for the diagnosis of the underlying renal osteodystrophic type. Al-staining techniques (Aluminum) were applied for detection of bone Al deposits. Additionally, bone Al content was determined quantitatively by means of graphite furnace atomic absorption spectroscopy. A mixed type of osteodystrophy (type III according to Delling's classification) consisting in the simultaneous presence of hyperparathyroid bone lesions (osteitis fibrosa, OF) and a hyperosteoidosis (osteomalacia, OM) was found in 63.3% of the studied patients. The other patients (37.7%) exhibited a pure osteomalacia (OM). Bone Al deposits at the mineralization front were observed in 70% of cases and were frequently associated with bone pain, spontaneous fractures and skeletal deformities. We conclude that bone biopsy should be performed in all patients presenting bone pain and high blood Al levels. PMID- 1303676 TI - Anti-diabetogenic effect of fusidic acid in diabetes prone BB rats. AB - Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs. In vitro studies have shown that they prevent the lymphocyte co-stimulatory activities of the cytokines IL-1 and IL-6 in a manner similar to that of cyclosporin A, and prevent the inhibitory effect of IL-1 on glucose-induced insulin production. As IL-1 and IL-6 are thought to play a role in the pathogenesis of Type 1 diabetes, the aim of this study was to investigate whether fusidin could influence the disease incidence of the spontaneously diabetic BB rat model. Accordingly, a group of 50 BB rats receiving fusidin dissolved in their drinking water were compared to a control group of 55 rats over a period of 200 days. The incidence of diabetes was found to be 52% in the experimental group and 71% in the control group (P < 0.05). The degree of insulitis and the number of islets at histological examination were similar among the non-diabetic animals whereas the diabetic fusidin-treated animals showed a higher degree of islet preservation than the diabetic control rats. The results are highly indicative of an anti-diabetogenic effect of fusidin. PMID- 1303677 TI - A new player in the antiphospholipid syndrome: the beta 2 glycoprotein I cofactor. AB - The study of antiphospholipid (aPL) antibodies has been greatly developed in recent years and conclusive evidence now exists concerning the correlation between aPL and clinical signs such as thrombosis, thrombocytopenia, abortion, and fetal loss. Several hypotheses have been put forward concerning the pathogenic mechanism of aPL, but none has received final confirmation from experimental data. Many studies have been devoted to characterizing the antigens recognized by the different aPL autoantibodies and to a cofactor involved in the binding of autoantibodies and phospholipids; this cofactor has been identified as an apolipoprotein, the beta 2 glycoprotein I (beta 2GPI) or APO-H. Direct evidence now exists which suggests that both the beta 2GPI and the phospholipid comprise the epitope to which aPL are directed. On the other hand anti-beta 2GPI antibodies have been identified in sera of patients suffering from SLE and primary Antiphospholipid Syndrome. beta 2GPI is normally present in human plasma/serum and possesses numerous inhibitory functions in multiple coagulation pathways. The amino acid sequence of beta 2GPI has been identified and found to consist of five repeating units that belong to the complement control protein (CCP) superfamily. This development of knowledge related to aPL has followed three steps respectively: 1. the standardization of the techniques of detection: 2. identification of the clinical signs related to the autoantibodies: and finally 3. the discovery of a new player, the beta 2GPI cofactor. PMID- 1303678 TI - Prevention of miscarriage in antiphospholipid syndrome. AB - Recurrent adverse pregnancy outcome may be the final result of different causes, including autoimmune diseases, as the Antiphospholipid Syndrome. Antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) were found in 16% of 197 patients with prior unexplained recurrent miscarriages. During our study 22 out of 32 antiphospholipid antibodies positive women became pregnant again. To prevent abortion relapses, 16 of them were treated with acetylsalicylic acid (50 mg x 2/day) and/or fluocortolone (20 mg/day for 5 days/week). Such therapy started as soon as pregnancy was diagnosed in 14 patients. Two patients began the therapeutic regimen during the third month of gestation. Six patients, who didn't accept this therapeutic approach, represent our control group. All the 14 early treated patients ended pregnancy with success. The 2 women that began the therapy later presented abortion relapses. Among the 6 not treated patients, 5 presented spontaneous abortion and only one gave birth to a baby. No side effect was observed neither in treated mothers nor in their babies. In conclusion, even if further studies would be necessary to standardise a therapeutic protocol, our results encourage the clinical care of patients with antiphospholipid antibodies and adverse pregnancy outcomes. PMID- 1303679 TI - Failure of blood mononuclear cells from human donors with autoimmune haemolytic anaemia to reconstitute severe combined immunodeficient mice. AB - The use of severe combined immunodeficient (SCID) mice to study humoral responses by peripheral blood mononuclear cells (PBMC) from patients with autoimmune haemolytic anaemia (AIHA) was assessed. Upon transfer to SCID mice, PBMC from normal donors and patients with autoimmune thyroid disease (AITD) produced substantial levels of immunoglobulin (Ig), detectable in the plasma of recipient SCID mice. In contrast, the majority of PBMC from AIHA donors did not produce Ig in recipient mice. The capacity of PBMC to reconstitute SCID mice was not related to the donor's age. In one case, remission of AIHA allowed the donor's PBMC to successfully reconstitute SCID mice, despite the fact that the donor had developed immune thrombocytopenic purpura (ITP). AIHA PBMC were viable by dye exclusion and contained cells in various states of activation, as judged by their IgG secretion profiles when cultured in vitro. The proportions of leukocytes in AIHA PBMC (T to B cell ratios, CD4+ to CD8+ cell ratios and monocytes) were highly variable compared to non-AIHA PBMC. To determine the effect of abnormal lymphocyte proportions on SCID reconstitution, depletion experiments were carried out on normal and AITD PBMC. This work demonstrated a requirement for high T cell numbers, especially CD4+ cells, and minimal B cell numbers for successful reconstitution. CD8+ depletion of PBMC led to increased levels of Ig production in some instances. It is considered that PBMC from AIHA patients have a defect different from that of other autoimmune disorders, which renders them incapable of reconstituting SCID mice. PMID- 1303680 TI - Suppression of experimental autoimmune uveoretinitis by intraorchidic administration of S-antigen. AB - Experimental autoimmune uveoretinitis (EAU) induced by immunization of albino Lewis rats with a retinal soluble antigen (S-antigen) has been studied extensively by many workers. An intraorchidic injection of S-antigen 4 days prior to immunization of the animal with the antigen emulsified in adjuvant was found to prevent the onset of the disease. Orchiectomy in 24 hr after the intraorchidic injection did not abolish the effect of treatment. The systemic suppression induced by the orchidic treatment persisted at least for 3 weeks after treatment. In rats that received orchidic treatment, delayed-type hypersensitivity was markedly inhibited but anti-S-antigen antibody levels in the serum were as high as those in immunized rats without orchidic pretreatment. These results indicate that antigen challenge to the testis is a novel method to systemic activation of the immunosuppressive mechanism. PMID- 1303681 TI - Protection against hyperglycemia in female nonobese diabetic mice treated with 15 deoxyspergualin. AB - The effects of 15-deoxyspergualin (15-DS), a newly described immunosuppressive agent, have been studied on the development of diabetes in female NOD mice. 15-DS treatment was started two weeks after weaning i.e. at five weeks of age. The mice received either one daily intraperitoneal injection of 15-DS (2.5 mg/kg body weight) or saline for two weeks. The mice were then injected every third day up to eight months of age for evaluation of the diabetes incidence. In another set of experiments the mice were treated up to three months of age, whereafter islet insulin release, islet insulin content and DNA content was measured together with an evaluation of spleen cell proliferation rates. Different spleen cell subsets were studied directly after the two weeks of daily injections. In the saline group 8 out of 9 mice developed diabetes, whereas only 4 out of 11 of the 15-DS treated mice became diabetic (p < 0.05). There was no difference between the groups in islet insulin release in response to glucose, however, the islet insulin release increased after one week in culture. The 15-DS treatment did not affect the insulin or DNA content of the isolated islets or the insulin concentration in the pancreas. No detectable changes in the relative number of CD4+ and CD8+ T-cell subsets in the spleen were seen and there were no obvious differences in splenocyte proliferation rates. The histological examinations of the pancreatic glands showed gradual increasing signs of islet inflammation with age and 15-DS could apparently not prevent this.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303682 TI - The Mycoplasma genitalium adhesin protein and several human class II MHC proteins exhibit sequence homology: possible ramifications for the development of autoimmunity. PMID- 1303684 TI - Autoantibodies to the Ro/SSA autoantigen are conformation dependent. II: Antibodies to the denatured form of 52 kD Ro/SSA are a cross reacting subset of antibodies to the native 60 kD Ro/SSA molecule. AB - The immune response to the Ro/SSA particles is conformation dependent. In sera with only anti-Ro/SSA precipitins, the autoantibodies to the 60 kD Ro/SSA are largely to the native 60 kD Ro/SSA while autoantibodies to the 52 kD Ro/SSA particle when present are exclusively to the denatured 52 kD Ro/SSA particle. Antibodies eluted from a recombinant 52 kD Ro/SSA fusion protein reacted in a sandwich ELISA which only measures antibody to native 60 kD Ro/SSA antigens and this reaction is largely inhibited by native homogeneous 60 kD Ro/SSA. In addition, antibody binding to the 52 kD Ro/SSA antigen in Western blot is also strongly inhibited by native 60 kD Ro/SSA. These experiment strongly suggest that reactivity of denatured 52 kD Ro/SSA antigen represents a cross reaction with autoantibodies directed to the native 60 kD Ro/SSA antigen. As a corollary of these experiments, data are presented that suggest the hY-RNAs are not associated with the 52 kD Ro/SSA protein but only with the 60 kD Ro/SSA protein. These data are consistent with the hypothesis that the autoanti-Ro/SSA response is driven by native 60 kD Ro/SSA and the immune response to denatured 52 kD Ro/SSA is largely a cross-reactive subset of the immune response to native 60 kD Ro/SSA. PMID- 1303683 TI - Variable region sequence of a human monoclonal thyroid peroxidase autoantibody. PMID- 1303685 TI - The role of capsular antigens in Staphylococcus aureus immunity. AB - Most clinical blood isolates of Staphylococcus aureus have been shown to be encapsulated. Techniques are now available for the preparation of type-specific capsular antisera and to provide reliable serologic methods for the identification of clinical isolates of Staphylococcus aureus. Epidemiologic studies in the U.S.A. and Europe indicated the prevalence of capsular types 5 and 8 among clinical isolates from human, bovine, and poultry. Encapsulated types 5 and 8 resisted in vitro phagocytosis and specific anti-capsular serum facilitated type-specific opsonization of S. aureus by polymorphonuclear leukocytes (PMN). The structure of the prevalent types 5 and 8 capsular polysaccharides (CP) have been elucidated. Vaccines of CP conjugated to exotoxin A of Pseudomonas aeruginosa have been prepared and have been injected into animals and human volunteers. Antibodies elicated by these conjugates facilitated opsonization of specific S. aureus types by human PMN. PMID- 1303686 TI - Composition of lipid A in the S and R forms of Shigella dysenteriae serovar 1. AB - A chemical analysis was performed of lipid A, isolated by acid hydrolysis of the lipopolysaccharide from the S and R forms of Shigella dysenteriae serovar 1. Differences in the moiety of both lipids and sugars were compared. The lipid portion consisted of a homologous series of fatty acids ranging from C12:0 to C18:0 (predominant homologues, C12:0, C14:0 and C16:0) and the homologous series of 3-hydroxy acids ranging from C12:0 to C16:0 (predominant homologue, 3-OH C14:0). The major sugar portion consisted of D-glucosamine. The toxicity of lipid A in mice (LD50) ranged between 300-400 micrograms/mouse, and values from the Limulus amebocyte lysate assay were recorded as titres of 10(-5) to 10(-6) mg/ml. PMID- 1303687 TI - Purification of Chlamydia psittaci antigen by affinity chromatography on polymyxin B agarose for use in the enzyme-linked immunosorbent assay (ELISA). AB - The purification of cell wall antigens of Chlamydia psittaci by affinity chromatography on polymyxin B agarose is described. Chlamydial cell wall antigens were prepared using different methods: heat treatment, ultrasonication and sodium deoxycholate treatment. The antigens were subsequently purified by gel chromatography. The highest amount of cell wall antigens was obtained by heat treatment of the chlamydiae at 90 degrees C and pH 8.5. The purified antigens showed molecular weights of 450 kDa to 700 kDa. Treatment of heat-extracted antigens with trypsin, pronase E or proteinase K did not destroy antigenic activity or alter the molecular weight. On the other hand, potassium metaperiodate treatment led to a significant decrease of both. Chlamydial cell wall antigens extracted by heat treatment and purified by affinity chromatography were used as ELISA-antigen. Using this ELISA and the complement fixation test (CFT), a total of 576 bovine sera was tested. 92 of these sera reacted positively in the ELISA and only 13 in the CFT. In addition, the prepared ELISA was compared with a commercial ELISA. 12 out of 15 sera tested were positive when using the ELISA described and 10 were positive when using the commercial ELISA. PMID- 1303688 TI - Evaluation of the polymerase chain reaction (PCR) for detection of Chlamydia psittaci in abortion material from ewes. AB - The polymerase chain reaction (PCR) was evaluated as a diagnostic tool for detection of Chlamydia (C.) psittaci in abortion material from 40 ewes. For this purpose, PCR results of 87 samples were compared with direct microscopic identification after chemical staining, cell culture isolation and a commercially available enzyme-linked immunosorbent assay (ELISA). The value for sensitivity as compared to cell culture was 97.7% whereas the specificity-value was calculated to be 84.1%. PMID- 1303689 TI - Computer-assisted identification of mycobacteria using code lists--results of a multi-centric study. German Working Group on Mycobacteria. AB - The frequency of isolation of environmental mycobacteria from clinical specimens has increased significantly in the course of the last years. Assessment of the medical importance of such isolates always depends on a correct identification of any of these strains. In a multicentric study, the efficacy of a standardized, computer-aided system for identification has been evaluated. 13 Laboratories received 24 strains of mycobacteria each and were asked to test all these strains for 16 different features. The results were coded in a standardized way. For the evaluation of these tests, the laboratories were supplied with a list containing all possible codes, which might be indicative of one or another identification. The results proved the logic of the approach. However, the application of the system lead to a correct identification in only 74% of all attempts. It is concluded that such a standardized approach is not useful for mycobacteria, because it requires too much working time and material. It will be more practical to concentrate on a smaller number of tests in the peripheral laboratories, which might allow the identification of M. tuberculosis and a few other species and to leave the definitive identification to reference laboratories. The development of faster, simpler and more reliable methods remains highly desirable. PMID- 1303690 TI - Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs? AB - The in vitro activity of 13 drugs against 552 clinical isolates of atypical mycobacteria representing 12 species was performed in 7H11 agar medium at the National Reference Laboratory for Mycobacteria, using the 1% proportion method. All the species tested were resistant to isoniazid and pyrazinamide. In general, clofazimine and D-cycloserine showed the widest spectrum of activity except in the case of Mycobactrium fortuitum and M. chelonei which were resistant to both drugs, and the M. szulgai and M. terrae complex which was resistant to D cycloserine. The next broad-spectrum drug was ethionamide, followed by ansamycin, rifampin, capreomycin, kanamycin, streptomycin and ethambutol. Among the fluoroquinolones, both ciprofloxacin and ofloxacin were active against M. xenopi, M. gordonae and M. fortuitum whereas M. kansasii and M. gastri were sensitive to ofloxacin only. When the species were listed in respect of the number of drugs to which they were susceptible (less than 10% of resistant strains), they were classified as follows; 7/13 drugs for M. kansasii, M. gastri and M. xenopi; 6/13 for M. gordonae; 5/13 for M. marinum; 3/13 for M. szulgai; 2/13 for M. fortuitum; 1/13 for the M. avium, M. scrofulaceum, M. simiae, and M. terrae complex, and none of the 13 in the case of M. chelonei. These results are discussed in relation to the multiple drug resistance of atypical mycobacteria. We conclude that the critical concentrations of drugs established for M. tuberculosis are not appropriate for atypical mycobacteria. PMID- 1303691 TI - Antibacterial in vitro-activity of meropenem against 200 clinical isolates in comparison to 11 selected antibiotics. AB - The antimicrobial activity of meropenem, a new parenteral carbapenem, was tested in vitro by an agar dilution method against 200 clinical isolates (gram negative/positive aerobes and anaerobes). Meropenem was compared with imipenem, ceftazidime, cefotaxime, piperacillin, ciprofloxacin, gentamicin; and metronidazole, cefoxitin, chloramphenicol, clindamycin, vancomycin when appropriate. Meropenem and imipenem exhibited an extended spectrum of activity with low minimal inhibitory concentrations (MICs). Only one strain each of Enterococcus faecium and Pseudomonas (Xanthomonas) maltophilia were resistant. Of the carbapenems, imipenem was slightly more active against Enterococcus faecalis, Streptococcus agalactiae, and staphylococci, but meropenem was obviously more active against enterobacteriaceae and Clostridium perfringens. Both, meropenem and imipenem had similar activities towards Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Streptococcus pyogenes and Bacteroides sp. All other antibiotics tested were less potent than the carbapenems with the exception of ciprofloxacin which generally exhibited similar antibacterial activities, except for anaerob microorganisms. PMID- 1303692 TI - Extracellular deoxyribonucleases of streptococci: a comparison of their occurrence and levels of production among beta-hemolytic strains of various serological groups. AB - Production of extracellular deoxyribonuclease by 394 strains of beta hemolytic streptococci was examined employing a deoxyribonucleic acid-methyl green assay. Enzymatic activities were measured in supernatants of bacterial cultures. Of the strains tested, 316 (80%) produced the enzyme. Nuclease production was demonstrated in 100% of group A strains and in 85, 74 and 58% of groups B, C and G, respectively. Levels of nuclease activity were then evaluated statistically. The analysis of variance showed that group A strains produced more enzyme than did streptococci of groups B, C or G. Group B strains produced less nuclease than did isolates of groups C or G. There was no significant difference in the levels of nuclease produced by groups C and G or by the various serological types of group B streptococci. Human group C strains produced more enzyme than animal strains. PMID- 1303693 TI - Prevalence of antibodies to Borrelia burgdorferi in serum and cerebrospinal fluid samples from patients with neurological disorders in Berlin. AB - Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological department were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by Western blotting a method for confirmation. 65 patients (8.1%) had serum IgG antibodies in ELISA and 22 of these patients (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titres in CSF by ELISA and 12 (1.5%) reacted in the Western blot. Clinical features of Bannwarth's syndrome were present in 12 patients (1.5%) and 4 patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were seropositive by both methods and 10 had elevated antibody activity in the CSF proved by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduced the number of false positive results but kept its standard in detecting antibodies in patients with active disease. PMID- 1303694 TI - Inflammatory signs, antibody response and antigen detection in cerebrospinal fluid over the course of neuroborreliosis. AB - CSF and serum specimens were consecutively obtained from three patients with neuroborreliosis (stage I, II and III), CSF protein content, cell counts and differential, IgG index, oligoclonal bands and anti-B. burgdorferi antibodies were measured. Cerebrospinal fluid (CSF) was tested for Borrelia-DNA being present prior to and after antibiotic treatment. While DNA could be identified before ceftriaxone was administered, there were no more amplification products afterwards. The goal of this study was to compare the usefulness of serodiagnostic methods and the detection of Borrelia burgdorferi-DNA in patients with clinically confirmed neuroborreliosis to test the efficiency of antibiotic therapy. PMID- 1303695 TI - Binding of Lactobacillus reuteri to fibronectin immobilized on glass beads. AB - Human fibronectin was immobilized on glass beads. The beads were used to evaluate binding of Lactobacillus reuteri to fibronectin. Organisms bound to the glass beads were detected using fluorescence microscopy after treatment with acridine orange. This binding was confirmed and quantified with the use of [3H]-labelled organisms. Three strains of Lactobacillus reuteri, three strains of Lactobacillus acidophilus and one strain of Lactobacillus fermentum were tested for binding capacity. L. reuteri strain 1063 exhibited a strong binding to the immobilized fibronectin, and L. acidophilus 1754 showed a slight binding. The binding of L. reuteri to the fibronectin was mediated by a protein as judged by the absence of binding after treatment of the bacteria with proteolytic enzymes. Treatment of the bacteria with urea, SDS and heat (80 degrees C) also reduced binding. Treatment of the bacterial cells prior to the assay with fibronectin interfered with binding. Albumin did not show this interaction. PMID- 1303696 TI - Adjuvant properties of Propionibacterium avidum KP-40 in vaccination against endemic viral and bacterial infections. II. Swine immunized with inactivated Haemophilus pleuropneumoniae vaccine and experimentally infected with different virulent serotypes of H. pleuropneumoniae. AB - Forty 3-month old swine were treated with immunomodulating Propionibacterium avidum KP-40 (PA) and/or vaccinated with a formalin-inactivated mixture of serotypes 1, 3, 5 and 9 of Haemophilus pleuropneumoniae (Pleurovac). Three weeks after revaccination all animals were inoculated with viable single serotypes of Haemophilus pleuropneumoniae. The IgG antibodies induced by vaccination agglutinated all serotypes of Haemophilus pleuropneumoniae, except for serotype 5. Antibody titers were not influenced by the application of PA together with the vaccine. Infection of vaccinated piglets resulted in the development of pleuropneumonia in 8 out of 10 animals, while vaccination together with application of PA lowered the morbidity rate to 1 out of 10 (p < 0.05). The usefulness of a PA prophylaxis was also demonstrated in non-vaccinated piglets infected with Haemophilus pleuropneumoniae. Because of the considerable variability of strains and serotypes of Haemophilus pleuropneumoniae and the generally low prophylactic potency of pleuropneumonia vaccines it is concluded that long-lasting enhancement of non-specific antiinfective resistance caused by PA may lower the risk of endemic infections in vaccinated piglets. PMID- 1303697 TI - Adjuvant properties of Propionibacterium avidum KP-40 in vaccination against endemic viral and bacterial infections. III. Swine immunized with live attenuated Erysipelothrix rhusiopathiae vaccine and experimentally infected with virulent strains R203 and R270B of E. rhusiopathiae. AB - Fifty 4-month old piglets were treated with immunomodulating Propionibacterium avidum KP-40 (PA) and/or immunized with live attenuated Erysipelothrix rhusiopathiae vaccine (Orvac). Four weeks after vaccination all animals were inoculated with viable Erysipelothrix rhusipathiae. The vaccine induced the appearance of high titers of specific IgG antibodies with peak values (1:115 1:200) three weeks after immunization. Administration of PA together with the vaccine did not influence antibody titers. Analysis of the course of experimental erysipelas infection in vaccinated and/or PA-treated swine revealed the prophylactic and beneficial effects of PA. PA-treated animals showed a significantly lower lethality rate than untreated controls and the course of the disease was considerably milder, with a shorter period of fever and a faster recovery. Vaccination provided good protection of swine against the development of erysipelas and therefore, the only significant difference in animals treated with PA applied together with the vaccine was a higher gain of body mass after infection. PMID- 1303698 TI - Detection of tick-borne encephalitis (TBE) virus in Liechtenstein. AB - In this study, we present the first detection of a focus of tick-borne encephalitis (TBE) virus-infected ticks in Liechtenstein. The focus is located on a much-used forest path near Vaduz, the capital of the principality. The virus isolated is a representative of the Western subtype of the TBE virus. It is thus closely related to or identical with the other strains isolated in western Europe. PMID- 1303699 TI - Isolation of Mycobacterium simiae from the environment. AB - An examination of 18 sphagnum samples collected in two different biotopes of the coastal region of southeastern Madagascar revealed an unexpectedly high positivity for mycobacteria (83.3%). The concentration of alcohol acid-fast bacilli reached a high level of 10(5) and 10(6)/g, respectively, compared with the sphagnum biotopes in moderate climates. Besides the habitat-specific mycobacterial species in sphagnum vegetation, like M. sphagni, M. gordonae and M. madagascariense, potentially pathogenic species, like M. avium, M. scrofulaceum and M. xenopi and M. marinum, were found. Furthermore, pathogenic M. simiae was found in sphagnum vegetation of Madagascar, first time isolated in the environment until now. It should be considered as a potential source of infection for human and animals. PMID- 1303700 TI - [Supranuclear disorders of eye movements. I. Disorders of saccades]. PMID- 1303701 TI - [Perimetry equivalents of glaucoma progression]. AB - Loss of sensitivity in chronic open-angle glaucoma is generalized, but heterogeneous. Particular parts of the visual field deteriorate proportionally, which also applies to the spatial behaviour. The proportionality factor and the slope of decay are most pronounced at the nasal and superior border of the field. In single cases, the topography of the field is variable, but it follows the retinal nerve fiber lines. For follow-up, topography seems to be unimportant. A number of standard threshold programs are adequate for this task. For follow-up the same type of instrument and the same program should always be used. The optimal value for analysis in perimetric follow-up is so far unknown. Although progression is often not linear, linear regression seems to be the most suitable statistical procedure. Some new methods of visualization help to process the information like the double representation, GATT, time diagram or the gray-scale bar. PMID- 1303702 TI - [3-dimensional topographic analysis of the papilla as a component of glaucoma diagnosis]. AB - Three-dimensional topography of the optic nerve head can be objectively described by means of quantitative parameter values. Owing to interindividual variability in the disc configuration, new structural variables, such as the relative height of the peripapillary retinal nerve fiber layer in stereo-videography and height variations in the contour line along the disc border in laser scanning tomography, have been shown to differentiate normal optic discs and optic nerve heads with pathological alterations better than standard volumetric data. Using laser scanning tomography, the effect of age on the parameter values of disc area, rim area and the ratio of the cup-to-disc area was evaluated in 61 healthy subjects (age 14 to 77) who had normal visual fields on computerized static perimetry. The rim area decreased with age (rs = -0.26, P < 0.05); the ratio of the cup area to disc area increased (rs = 0.25; P < 0.05). No relationship was found between patient age and disc area (Spearman correlation). Although the coefficients of correlation are rather small, they may reflect the physiological age-related decline in axonal count. The high resolution of strictly confocal laser scanning microscopy allows for visualization of nerve fiber bundle defects underneath a surface of regular reflectivity. The existence of such hidden nerve fiber bundle defects has been postulated before on the basis of experimental studies and may be an early morphological sign of glaucomatous damage. PMID- 1303703 TI - [Glaucoma parameters of the papilla. Comparison of clinical and stereophotography methods with laser scanning tomography]. AB - The observations recorded by laser tomographic scanner (LTS) and with clinical and stereophotographic evaluation of 40 optic discs in the same glaucomatous patients were compared. Quantitative parameters (vertical and horizontal cup-to disc ratio) and qualitative parameters (nasal excavation, notch, pseudo-pit, overpass, bayonetting) were evaluated. The correlation coefficients for the quantitative parameter ranged from 0.59 to 0.73. The definition of excavation used meant that the values found with the LTS were consistently higher. The qualitative parameter did not differ significantly with the method. Therefore, the LTS can be considered equivalent to the standard methods. PMID- 1303704 TI - [Contact cyclophotocoagulation with the continuous wave Nd:YAG laser with quartz fiber. Optimizing coagulation parameters]. AB - Transscleral cyclo-photocoagulation with a cw-Nd:YAG-laser was studied in enucleated porcine eyes with application times of between 10 ms and 1.5 s. Contact coagulation via a quartz fiber (core 600 microns) required about 32% less power to create visible ciliary body coagulation compared to non-contact coagulation via a focusing handpiece. Application of focusing fiber tips led to a further reduction in the coagulation threshold by a factor of 0.6. The energy per laser application required for ciliary body coagulation increased with application time. During contact coagulation using plane fiber tips a pronounced temperature rise was sometimes observed at the fiber tip due to deposits of carbonized tissue with the subsequent risk of scleral damage. In a pilot study five eyes with secondary glaucoma were treated under coagulation conditions found to be optimal (8 W at 0.2 s). PMID- 1303705 TI - [New aspects of surgical treatment of glaucoma. Comparison of viscoelastic substances in chamber angle surgery]. AB - The development of new viscoelastic substances opens up new perspectives for chamber angle surgery under direct view. The success of "Cyclodialysis ab interno" treating children with glaucoma is often reduced by scar formation of the cleft. Therefore four different viscoelastic substances were instilled during an animal experimental study into the cleft and compared in their effect. We used hyaluronic acid with different molecular weight (Healon and Healon GV) and cross linked forms of hyaluronan as a fluid and a gel (Hylan fluid and Hylan gel). A cyclodialysis ab interno was performed on 14 eyes of cynomolgus monkeys. The functional results (tonometry, outflow facility, autoradiography) and the morphological findings will be presented and their consequences for an extended indication of the cyclodialysis ab interno will be discussed. PMID- 1303706 TI - [Echographic follow-up of the chamber angle in suspected simple glaucoma]. AB - We have recently seen a number of patients with angle-closure glaucoma who had been treated for glaucoma simplex (primary open-angle glaucoma). The main cause of this misdiagnosis was gonioscopy, as its findings are subject to the impression of the examiners. For objective examination of the chamber angle and the iris configuration, B-scan ultrasonography was performed using a contact eye cup filled with saline. Two groups of patients were noted in particular. The first group contained relatively young patients, more men than women, with plateau iris and a central normal, deep anterior chamber. The second group consisted of patients with presumed glaucoma simplex. The findings were quite different between eyes. In the eye with a higher IOP, pronounced optic nerve damage and visual field defect, the chamber angle was distinctly more narrow and closed. Most of the patients were treated with beta-blocker drops, which they felt were agreeable. PMID- 1303707 TI - [Tarsoconjunctival transposition. Causes, prevention and possibilities for correction of postoperative complications]. AB - The Hughes' tarsoconjunctival flap technique has proved to be a reliable operative procedure for the treatment of large lower-lid defects for more than 55 years. The Hughes' procedure has maintained its importance despite the development of numerous other operations, two reasons for this being that there have now been several modifications to this technique and that the lids do not have to be closed as long. To help the surgeon avoid and eliminate problems and errors in the operative technique we provide details and some useful tricks we have learned over the years while treating over 50 patients. The causes, prophylaxis, and correction of postoperative complications are described for the following: lowering the lid margin; thinning of the lid in the area of the tarsal transposition; lymph edema of the transplant; lid margin defects, and dehiscence of the wound; corneal epithelial defects; trichiasis caused by lanugo hair; keratinization of the lid margin; ectropion of the conjunctiva; retraction of the upper lid, and entropion of the upper lid. If these details are taken into consideration, the Hughes' procedure is a simple operative technique that is free of serious complications and gives good results in the reconstruction of the lower lid. PMID- 1303708 TI - [Diagnosis and therapy of chronic canaliculitis]. AB - The chronic lacrimal canaliculitis is often overlooked and unsatisfactory treated. The purpose of this long-term study (1978-1991) is to call attention to special bacteriological signs and to give recommendations for proper treatment. 54 patients (39 females and 15 males) in age from 29 to 85 years (average age of 60 years) with a chronic lacrimal canaliculitis were evaluated. "Sulfur granules" were obtained from 32 patients and 54 specimens were collected from 44 patients and processed immediately for aerobic and anaerobic cultivation as well as microscopic investigation. Altogether 100 bacteria could be isolated: 56 anaerobes, 38 aerobes as well as 6 microaerophilic and capnophilic strains, respectively. Members of the genus Actinomyces were the most often isolated anaerobes. They could be detected in specimens of 15 patients by culture and in materials of 4 patients only by microscopic study. 42 from 50 patients were permanently cured by immediate treatment according to our operative procedure despite the splitted canaliculus. The most common cause of chronic lacrimal canaliculitis is a mixed infection. Despite the characteristic clinical symptoms the laboratory evaluation should be done to provide the diagnosis. The surgical procedure leads to a permanent functional healing in a high degree. PMID- 1303709 TI - [N2 cryotherapy and excision. Indications and limits in eyelid basalioma]. AB - Some ophthalmic surgeons have preferred N2-cryosurgery for many years. Others feel that only excisional surgery should be used. In this article both possibilities are discussed in an effort to facilitate a well-balanced choice. A total of 262 basalioma patients treated by cryosurgery from 1979 to 1988 were evaluated to assess the indications for cryosurgery. The histological findings were taken into consideration, as were the results of other authors. The comparison with histopathologically controlled excisions was based on discussions with users of the Mohs technique, literature, and personal experience. No other technique permits as much healthy tissue to be saved as N2-cryosurgery; this is especially important in the areas of the lid margin and lacrimal pathways. Complete involvement of the tumor edges can be achieved by generous extension of the treatment area and biopsies taken beyond the expected tumor margins and tumor base (subsequent to tunneling and cryosurgery from the basal side). In excisional surgery, the Mohs technique is required. Its advantage is that biopsies can be taken all around the tumor for histology and its disadvantage is prolonged operation time (in ad hoc frozen sections) or delayed wound closure (second or third surgical procedure several days later). This can be avoided in tumors that are suitable for cryosurgery. The Mohs technique, however, is mandatory in deeply infiltrating tumors in which cryosurgery is not indicated. The two methods complement one another. This is supported by the long-term results. PMID- 1303710 TI - [Gold implantation in lagophthalmos]. AB - In 20 patients with irreversible facial palsy, dynamic voluntary lid closure was achieved by implantation of 0.8-1.6 g gold weights in the upper lid. Because of the high rate of efficiency, low complication rate and technical simplicity, this method is recommended more often than comparable procedures (magnet or wire spring implantation). PMID- 1303711 TI - [Documentation of digital dacryocystography using video technique]. AB - Digital dacryocystography is considered the optimal radiodiagnostic method in obstructions of the lacrimal pathways. The examination is carried out by a computer-controlled X-ray unit with a C-arc attached to an image-intensifying TV system. In this way the advantages of this technique and of modern video recording are linked. The bilateral filling process of the contrast medium is recorded and the findings simultaneously recorded on videotape. Consequently, pictures of the dynamic flow are retrievable at any time. This provides good diagnostic documentation and an outstanding basis for any scientific analysis. PMID- 1303712 TI - [Ewald Hering's opponent colors. History of an idea]. AB - Ewald Hering (1834-1918) was one of the founders of modern visual science. Among his contributions, his color concept gave rise to mostly fruitless controversies, because it appeared to be incompatible with the trivariance of vision theory put forward by Young and Helmholtz. It is now clear that the two color concepts can be reconciled with one another. Hering's theory is based upon an analysis of visual perception. Experience indicates that a conscious subject needs four unique colors in order to characterize perception: blue, yellow, red and green. Usually, two of these hues, but never more, constitute a color sensation, e.g., orange contains red and yellow while blue and green are the components of turquoise. The central idea in Hering's concept was that red and green are opposite hues because they are never elicited simultaneously by a color stimulus; the same is true for blue and yellow. Hering also postulated that the perception of opponent colors is mediated by opponent processes in certain elements of the nervous system, i.e., that there are neurons that respond in a qualitatively different way to spectral stimuli of different frequencies. Today we know that, in fact, the majority of neurons in the retina and the visual pathway is capable of opponent-type responses as anticipated by Hering. It was, however, a long way until his concept was understood and finally accepted by the science community. Among those who helped to acknowledge it were the German physiologist von Kries, the Austrian physicist Schrodinger, the Finnish neurophysiologist Svaetichin, and the American psychophysicists Hurvich and Jameson. In 1906, the German Ophthalmological Society honored Ewald Hering by awarding him the Albrecht von Graefe Medal. PMID- 1303713 TI - Nursing diagnosis: implications for health, with particular concerns for community nursing. AB - As nursing terminology develops to include positive health/wellness related concepts, the appropriateness of nursing diagnoses is questioned. Nursing diagnoses have the potential to lead community nurses towards a reductionist and simplistic view of the complexities associated with community issues. Concerns and questions are raised in relation to the acceptance of nursing diagnoses in Australian community nursing practice. PMID- 1303714 TI - Nursing's need for leadership. PMID- 1303715 TI - Reform in higher education for nurses: comparative comments from Canada. AB - This article compares the move of basic nursing education in Australia into the university sector with the status of higher education for nursing in Canada. The influence of nursing unions and nursing associations in nursing education, and the role of human resource planning and development in nursing are addressed. Four major issues confronting university-based education are explored: essential qualities of nursing education, content versus process curricula, transition of faculty into academia, and relationships with other disciplines, especially medicine. PMID- 1303716 TI - Maternal-infant health beliefs and infant feeding practices: the perception and experience of immigrant Vietnamese women in Sydney. AB - The purpose of this study was to describe and compare the health beliefs and infant feeding behaviour of Vietnamese women before and after immigration to Sydney. Findings from 20 in-depth face to face interviews conducted in the women's homes revealed that infant feeding behaviour was shaped by the women's beliefs about maternal, infant and family health. Through a process of adaptation these health beliefs had been modified under the influence of the social, cultural, and economic environment of the host country. The findings offer a greater understanding of Vietnamese culture and infant feeding behaviour on which to base nursing intervention programs to promote breast feeding. PMID- 1303717 TI - Reflections on Benner: a critical perspective. AB - This paper examines the theoretical perspective of Patricia Benner (1984; 1989) as outlined in two of her recent works. The evaluative criteria used are the critical perspective developed by Carr and Kemmis (1986). The interpretive strengths of her work are identified and extended by comparison with the work of Lawler (1991). Problems in Benner's analyses are found to centre around the weaknesses of the interpretive perspective. An analysis of the structural constraints that act to distort the interpretation of nurses' work is offered as an alternative. An evaluation is given of the relevance to practice of Benner's work. PMID- 1303718 TI - Enrolled nurse education. PMID- 1303719 TI - How nursing research resolved my professional identity crisis. PMID- 1303720 TI - Nurses for peace and the environment. PMID- 1303721 TI - What's right in university writing? PMID- 1303722 TI - Physical assessment by nurses: a study of nurses' use of chest auscultation as an indicator of their assessment practices. AB - A non-experimental survey was conducted to determine if the factors such as years of practice, how physical assessment skills were learnt and how often these skills were utilised, influenced nurses' reluctance to implement physical assessment. A sample of 150 registered nurses was surveyed. Analysis indicated that the majority of respondents has been taught to listen to chest sounds (auscultation) but did not implement this skill on a daily basis. Chi square analysis indicated that younger nurses with less years of experience were more keen to learn chest auscultation skills than nurses who were older and had more years of nursing experience. PMID- 1303723 TI - The unresponsive person. PMID- 1303724 TI - Primary health care in nursing practice. PMID- 1303725 TI - The adjuvant potential of cytokines. PMID- 1303726 TI - Metabolic activation of phenols by stimulated neutrophils: a concept for a selective type of anti-inflammatory drug. AB - Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent and selective inhibitor of neutrophil oxyradical production. The mechanism of action involves metabolic activation in a (myelo)-peroxidase-dependent reaction. The reaction product(s) prevent(s) the assembly of the superoxide anion-generating NADPH:O2 oxidoreductase by conjugation to essential thiol groups. Different neutrophil functions that are essential to their bactericidal activity, however, remain intact. When administered orally a potent anti-inflammatory activity was found in rats with experimentally induced local or systemic inflammation. PMID- 1303728 TI - An immunodominant antigen of Giardia lamblia is a heat shock protein. AB - In this study we demonstrate that an immunodominant antigen of Giardia lamblia is a heat shock protein. The expression of the antigen was induced not only by heat shock but also when Giardia trophozoites were placed in media more closely resembling the environment in the host, indicating that this antigen may play an important role in host-parasite interactions. PMID- 1303727 TI - Human B-cell growth-inhibitory activity of eosinophil cationic protein. AB - The effect of eosinophil cationic protein (ECP) upon proliferation of human B cell lines or purified B cells was studied. ECP inhibited proliferation of the human lymphoblastoid cell lines CBL and GM-1056 at doses of 0.1-5 ng/mL during 2 4 days of culture. The inhibitory effect of ECP was reversible and not due to toxic damage. Moreover, inhibition could be blocked by anti-ECP serum while the control serum failed to do so. Of various cytokines tested--including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6; interferon (IFN)-alpha or IFN-gamma- IL-4 reduced the inhibition, while other cytokines failed to do so. The reduction of inhibition was specific to IL-4 since reduction by IL-4 was blocked by anti-IL 4 antibody but not by the control antibody. ECP also inhibited proliferation of tonsillar small resting B cells stimulated with anti-mu antibody plus low molecular weight B-cell growth factor (BCGF) or of large activated B cells. In contrast, ECP had no effect on proliferation of unstimulated small resting B cells. This inhibition was also reduced by IL-4 specifically. These results indicate that ECP may also act as a B-cell regulating factor. PMID- 1303729 TI - Solid-phase syntheses of two deacetyl-thymosin alpha 1 analogues with substitution at position 21 and their effects on low E-rosette-forming lymphocytes of uremic patients. AB - Two deacetyl-thymosin alpha 1 analogues containing Phe or Phe(4F) at position 21 were synthesized by the manual solid-phase method and their immunological effects on the low E-rosette-forming lymphocytes of uremic patients were studied. Fluorination of the p-position of Phe21 resulted in a marked restorative effect on the low E-rosette-forming lymphocytes of uremic patients compared with that of [Phe21]deacetyl-thymosin alpha 1. The synthetic [Phe21]deacetyl-thymosin alpha 1 was approximately equal in potency to our synthetic deacetyl-thymosin alpha 1 in uremic patients. PMID- 1303730 TI - Transforming growth factor-beta 1 inhibits postischemic increases in splanchnic vascular resistance. AB - Anesthesized male rabbits having a resting mean arterial pressure of 81 +/- 4 mm Hg and superior mesenteric artery blood flow of 91 +/- 7 mL min-1 were subjected to 60 min of splanchnic ischemia followed by 60 min of reperfusion. Upon reperfusion, mean arterial pressure fell. Splanchnic blood flow also decreased but not in parallel with blood pressure; consequently, vascular resistance was increased over the reperfusion period. This increase in splanchnic vascular resistance was not affected by intravenous t-PA (0.5 mg kg-1 + 5 mg kg-1 hr-1) for 30 min prior to and throughout the reperfusion period or by intravenous L NAME (1 mg kg-1 x 2). However, intravenous infusions of TGF-beta (18 or 54 micrograms kg-1) at the time of reperfusion dose dependently attenuated the increases in vascular resistance (p < 0.05). This effect of TGF-beta was enhanced by coadministration of t-PA and inhibited by the coadministration of L-NAME. We propose that the effects of TGF-beta are ultimately mediated via nitric oxide release, and conclude that this may be useful therapy for the prevention of reperfusion-associated injury following surgery or as an adjunct to thrombolytic therapy. PMID- 1303731 TI - Localization of subspecies of protein kinase C in the mammalian central nervous system. AB - Activation of protein kinase C (PKC) is regulated by dual second messengers; diacylglycerol (DG) produced by receptor mediated hydrolysis of phosphatidylinositol and Ca2+ which is released by inositol 1,4,5-triphosphate (IP3) from intracellular stores in the endoplasmic reticulum. In the mammalian central nervous system, available evidence suggests that PKC plays a prominent role in the processing of neuronal signals and in the short-term or long-term modulation of synaptic transmission. This enzyme is a member of a family consisting of at least eight subspecies, alpha, beta I, beta II, gamma, delta, epsilon, zeta and eta. The homologous structure of each subspecies makes difficult resolution of the enzymological properties of the enzyme. The distinct functional roles of PKC subspecies in mammalian tissues have been elucidated by defining the localization of each subspecies. We identified alpha-, beta I-, beta II- and gamma-PKC subspecies in the rat brain by in situ hybridization and by light and electron microscopic immunohistochemistry, using antibodies specific for each subspecies. Most immunoreactions of the alpha, beta I, beta II and gamma subspecies were evident in neurons and there were few, if any, in glial cells. In this article, we summarize known cellular and subcellular localizations of PKC subspecies in mammalian CNS and some aspects of current studies in neuronal functions regulated by this enzyme are discussed. PMID- 1303732 TI - Blood-brain barrier transfer of L-Trp and alpha-MTrp in Li-treated rats. AB - Blood-brain barrier (BBB) transport for L-Trp and alpha-methyl-L-tryptophan was evaluated in Li-treated rats. Five different brain areas as well as left to right differences were examined. No left to right difference in the PS product was observed. Lithium treatment had a significant effect on the plasma concentration of Val, Leu and Ile but no effect on plasma total or free Trp. The ratio of plasma Trp to the sum of Leu, Val, Ile, Phe, Met and Tyr is increased in the Li treated rats but not significantly. However, the ratio of Trp/(Val+Leu+Ile) is significantly increased in the Li-treated rats. The Km apparent (Kmapp) for the BBB Trp transport is significantly decreased (affinity of the carrier for Trp is increased) in the Li-treated rats. A decrease in the Kmapp is one of the possible factors responsible for an increase in the brain Trp concentration and subsequent increase in the brain serotonin synthesis in Li-treated rats. PMID- 1303733 TI - Characterization of cocaine-sensitive dopamine uptake in PC12 cells. AB - Dopamine uptake in rat pheochromocytoma (PC12) cells is a carrier-mediated process which follows Michaelis-Menten kinetics. Uptake was saturable with an apparent Km of 0.71 microM for dopamine and a Vmax of 3.2 pmol/2 x 10(5) cells/min. The rank order of potency for various amines was norepinephrine > or = dopamine > epinephrine. Uptake increased with increasing temperature and showed a sharp break in the Arrhenius plot at 27.5 degrees C. The Q10 was 1.39 above and 2.95 below 27.5 degrees C. Cocaine inhibited uptake in a dose-dependent manner with a Ki of 0.97 microM. The presence of cocaine lowered the apparent Km but did not affect the Vmax, indicating competitive inhibition. Tunicamycin inhibited [3H]dopamine accumulation in a dose- and time-dependent fashion suggesting the dopamine uptake site in PC12 cells is an asparagine-linked glycoprotein. Kinetic analysis showed a decrease in Vmax but not in the apparent Km after tunicamycin treatment, consistent with the notion that tunicamycin treatment results in the loss of a substantial amount of active carrier molecules. PMID- 1303734 TI - Protease activities in carp retina. AB - Protease of carp retina were examined by electrophoresis and fluorogenic assays. A 70 kD serine protease with an alkaline pH optimum was detected in gelatin containing polyacrylamide gels. A similar enzyme was found in carp brain and muscle, but not in lens. Using aminomethylcoumarin (MCA) substrates, activities that hydrolysed Z-Phe-Arg-MCA, Boc-Ala-Gly-Pro-Arg-MCA and various aminoacyl-MCAs were detected. The Z-Phe-Arg-MCA hydrolase was an acidic cysteine protease, whereas the Boc-Ala-Gly-Pro-Arg-MCA hydrolase was an alkaline cysteine protease. All aminoacyl hydrolase activities tested were inhibited by bestatin and o phenanthroline, but not by inhibitors of serine, cysteine and aspartic proteases, suggesting they are metalloaminopeptidases. Of the substrates tested, Tyr-MCA was the most readily hydrolysed aminoacyl substrate. Preliminary evidence was obtained suggesting that levels of these activities do not differ between light- and dark-adapted retinae. The proteases have a potential involvement in retinal functioning and show similarities to other proteases known to act in the central nervous system. In particular, the Tyr-MCA hydrolase may be related to an enzyme known to remove the N-terminal tyrosine residue from enkephalin. PMID- 1303735 TI - Regulation of tubulin, Tau and microtubule associated protein 2 expression during mouse brain development. AB - The level of three microtubule proteins, tubulin, Tau and MAP2 and of their encoding mRNA was studied in the mouse brain at an early developmental stage (3 days postnatal) and in adulthood. The level of the mRNA encoding both tubulin and Tau decreased by 85% between these two stages whereas the encoded proteins decreased only by 50% during the same period. Thus, the level of these proteins seems to be regulated both negatively and positively by transcriptional and post translational mechanisms. In vitro transcription assays, performed with nuclei isolated at different postnatal stages, showed that the tubulin and Tau transcripts are produced with some variations during mouse brain development. However these fluctuations are much less important than the drops of the steady state levels of tubulin and Tau mRNA seen in vivo. Thus, the decrease in transcripts levels does not seem to result from reduced transcriptional activities, and can be ascribed to changes in mRNA stability occurring during brain development, i.e. to a post transcriptional mechanism. The situation is even more complex for MAP2: its encoding mRNA level remains constant during development whereas the in vitro transcription activity decreases markedly during the same period. Finally, MAP2 protein level increases during development although its encoding mRNA level remains constant suggesting that this protein is stabilized by a post translational mechanism. PMID- 1303736 TI - Grafting of genetically modified cells: effects of acetylcholine release in vivo. AB - In this study, microdialysis was used to investigate functional recovery of central cholinergic neurons in the forebrain of rats with cortical devascularizing lesions. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and genetically modified fibroblasts secreting nerve growth factor (NGF) were placed at the site of the lesion. One month following surgery, microdialysis probes were installed in the remaining cortex and were perfused with artificial cerebrospinal fluid (csf) containing neostigmine (5 nM) and/or KCl (100 mM). The basal (non-stimulated) release of acetylcholine (ACh) in the cortex was similar in all experimental groups, whereas KCl stimulated release of ACh was significantly augmented (P < 0.05) in the ipsilateral remaining cortex in lesioned animals that have been implanted with fibroblasts secreting NGF. These results suggest that NGF secreted by genetically engineered fibroblasts modulates neuroplasticity in the adult mammalian CNS and may favour recovery of cortical function following injury. PMID- 1303737 TI - A novel glycosignaling system: GQ1b-dependent neuritogenesis of human neuroblastoma cell line, GOTO, is closely associated with GQ1b-dependent ecto type protein phosphorylation. AB - Previously, we reported that ganglioside GQ1b specifically promoted neuritogenesis of human neuroblastoma cells (GOTO), and also that is specifically stimulated the phosphorylation of several cell surface proteins on the same cells. To disclose the relationship between the two events, we examined them using a novel protein kinase inhibitor, K-252b, which is a derivative of K-252a and cannot pass through cell membrane. K-252b inhibited the GQ1b-dependent neuritogenesis as well as the GQ1b-stimulated phosphorylation. This suggests the direct coupling between the two cell events and the occurrence of a new biosignal transduction system. PMID- 1303738 TI - Differential stimulation of hepatic and brain metallothioneins by ethanol. AB - Administration of ethanol induces the synthesis of hepatic metallothionein and metallothionein mRNA in the liver but not in the brain. Furthermore, ethyl alcohol, methyl alcohol and isopropyl alcohol enhance the synthesis of metallothionein in Chang cells but not in neuroblastoma IMR-32 cells in culture. The results of this study are interpreted to suggest that the mechanisms of synthesis of metallothionein and the utilization of essential metal nutrients in the brain and peripheral tissues are not identical. PMID- 1303739 TI - Characterization of phospholipase A2 and acyltransferase activities in squid (Loligo pealei) axoplasm: comparison with enzyme activities in other neural tissues, axolemma and axoplasmic subfractions. AB - Phospholipase A2 and acyltransferase were assayed and characterized in pure axoplasm and neural tissues of squid. Intracellular phospholipase A2 activity was highest in giant fiber lobe and axoplasm, followed by homogenates from retinal fibers, optic lobe and fin nerve. In most preparations, exogenous calcium (5 mM) caused a slight stimulation of activity. EGTA (2 mM) was somewhat inhibitory, indicating that low levels of endogenous calcium may be required for optimum activity. Phospholipase A2 was inhibited by 0.1 mM p-bromophenacylbromide, and was completely inactivated following heating. The level of acylCoA: lysophosphatidylcholine acyltransferase activity was higher in axoplasm and giant fiber lobe than in other neural tissues of the squid. Km (apparent) and Vmax (apparent) for oleoyl-CoA and lysophosphatidylcholine were quite similar for axoplasm and giant fiber lobe enzyme preparations. Acyltransferase activity was inactivated by heat treatment, and greatly inhibited by 0.2 mM p chloromercuribenzoate, and to a lesser extent by 20 mM N-ethylmaleimide. Phospholipase A2 activity was present in fractions enriched in axolemmal membranes (separated from squid retinal fibers and garfish olfactory nerve) from both tissues, and it was also highly concentrated in vesicles derived from squid axoplasm. In all three preparations, phospholipase A2 activity was stimulated by Ca++ (5 mM) and inhibited by EGTA (2 mM). In addition, axoplasmic cytosol (114,000 g supernatant) retained a substantial portion of a Ca(++)-independent phospholipase A2, active in the presence of 2 mM EGTA. Acyltransferase activity was present at high content in both axolemma membrane rich fractions, and among subaxoplasmic fractions and axoplasmic vesicles. PMID- 1303740 TI - Striatal quinolinic acid lesions increase [3H]WIN 35,428 binding to the dopamine transporter. AB - Striatal quinolinic acid lesions have been used as a model for the pathology seen in Huntington's disease. Seven days following a unilateral injection of 100 nmol of quinolinic acid into the rat caudate-putamen (striatum), a large increase in the binding of [3H]WIN 35,428 to the lesioned caudate-putamen was seen when compared to the unlesioned side. Binding in other brain regions was unchanged. These data indicate that there is an increase in dopaminergic uptake sites in the lesioned caudate-putamen and suggest a target for further study in Huntington's disease. PMID- 1303741 TI - Differential production of prostaglandins D2 and E2 and of an unusual prostanoid by chick spinal cord and meninges in vitro. AB - In order to specify the source of locally synthesized prostaglandin (PG) E2 which is able to saturate the large class of low affinity PGE2 receptors in chick spinal cord, bioconversion of [1-14C]arachidonic acid into prostanoids was studied in homogenates of chick spinal cord and meninges first without addition of exogenous glutathione (GSH). Homogenates of spinal cord produced 14C-labeled PGE2, PGD2 and PGF2 alpha. Homogenates of meninges accumulated much larger amounts of [14C]PGE2 than spinal cord and surprisingly a 14C-labeled arachidonate metabolite referred to as compound Y. Compound Y generation, which was inhibited by indomethacin and enhanced by esculetin, was therefore mediated through the cyclooxygenase pathway. The fact that no labeled compound Y was detected in homogenates incubated with [3H]PGD2 or [3H]PGE2 indicated that compound Y was not a degradation product of PGs. Secondly, after addition of exogenous GSH, 14C labeled compound Y was totally converted into [14C]PGE2. The compound Y which is converted into PGFs after a strong reduction with NaBH4 and into PGE2 after a mild reduction with GSH-hemin system or SnCl2 was therefore assumed to be a 15 hydroperoxy-PGE2 (15 HP-PGE2). These results suggest that PGE2 can be synthesized in meninges either by the classical isomerization of PGH2 or by isomerization of PGG2 followed by a GSH-sensitive reaction. PMID- 1303742 TI - Malnutrition increases insoluble-to-soluble tubulin ratio and in vitro incorporation of 32ATP in rat cerebral cortex. AB - Wistar rats were fed a normal protein (25% casein) or an isoenergetic low protein (8% casein) diet from the day of birth to weaning on day 21. Litters were killed at weaning and cerebral cortex was removed. Tubulin was prepared by centrifugation at 100,000 g, 4 degrees C, as described by Shelansky et al. [Proc. Natn. Acad. Sci. U.S.A. 70, 765-768 (1973)]. Cold-insoluble tubulin was recovered in the pellet (P1) fraction and cold-soluble tubulin in the supernatant (S1) fraction. Alpha and beta tubulin were quantified by electrophoretic and immunological methods in both fractions. Our results indicated that malnutrition enhanced the ratio of cold-insoluble-tubulin-to-cold-soluble-tubulin. Furthermore malnutrition induced an increased in vitro incorporation of 32P into both soluble and insoluble tubulins. Although tubulin phosphorylation has been related to tubulin stability properties, we cannot unequivocally ascribe the increased insoluble/soluble tubulin ratio with malnutrition to increased in vitro incorporation of 32P. PMID- 1303743 TI - Time-resolved protein crystallography. AB - Advances in synchrotron radiation technology have allowed exposure times from protein crystals of the order of milliseconds to be used routinely, and in exceptional circumstances exposure times of 100 ps have been obtained. However, many data sets take seconds to record because of the slow time scale of film change or crystal reorientation or translation when more than one exposure is required. This problem has been addressed by Amemiya et al. (1989). There has been considerable progress in methods to initiate reactions in protein crystals, especially the development of photolabile caged compounds but also temperature jump, pH jump, and diffusion. Although flash lamps deliver pulses of 100 mJ/ms, often several pulses are required to release sufficient product, and reaction initiation can take several seconds. Laser illumination can provide more powerful input, but the laser must be accommodated within the restricted space at the synchrotron station. The requirement to maintain synchrony among the molecules in the crystal lattice as the reaction proceeds and to ensure that the lifetime of intermediates is longer than data collection rates emphasizes the need for chemical characterization of the reaction under study. As Ringe advocated in the studies with chymotrypsin, it may be more profitable to devise conditions under which certain intermediates along the reaction pathway accumulate in the crystal and to record these in a series of discrete steps rather than continuous monitoring of the reaction. The Laue method is limited to those proteins that give well-ordered crystals and problems of transient disorder on initiation of reaction and problems of radiation damage need to be overcome or avoided by suitable experimental protocols.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303744 TI - Macromolecular crystal growth experiments on International Microgravity Laboratory--1. AB - Macromolecular crystal growth experiments, using satellite tobacco mosaic virus (STMV) and canavalin from jack beans as samples, were conducted on a US Space Shuttle mission designated International Microgravity Laboratory--1 (IML-1), flown January 22-29, 1992. Parallel experiments using identical samples were carried out in both a vapor diffusion-based device (PCG) and a liquid-liquid diffusion-based instrument (CRYOSTAT). The experiments in each device were run at 20-22 degrees C and at colder temperatures. Crystals were grown in virtually every trial, but the characteristics of the crystals were highly dependent on the crystallization technique employed and the temperature experience of the sample. In general, very good results, based on visual inspection of the crystals, were obtained in both PCG and CRYOSTAT. Unusually impressive results were, however, achieved for STMV in the CRYOSTAT instrument. STMV crystals grown in microgravity by liquid-liquid diffusion were more than 10-fold greater in total volume than any STMV crystals previously grown in the laboratory. X-ray diffraction data collected from eight STMV crystals grown in CRYOSTAT demonstrated a substantial improvement in diffraction quality over the entire resolution range when compared to data from crystals grown on Earth. In addition, the extent of the diffraction pattern for the STMV crystals grown in space extended to 1.8 A resolution, whereas the best crystals that were ever grown under conditions of Earth's gravity produced data limited to 2.3 A resolution. Other observations indicate that the growth of macromolecular crystals is indeed influenced by the presence or absence of gravity. These observations further suggest, consistent with earlier results, that the elimination of gravity provides a more favorable environment for such processes. PMID- 1303746 TI - On the multiple simultaneous superposition of molecular structures by rigid body transformations. AB - A method of optimally superimposing n coordinate sets on each other by rigid body transformations, which minimizes the sum of all n (n - 1)/2 pairwise residuals, is presented. In the solution phase the work load is approximately linear on n, is independent of the size of the structures, is independent of their initial orientations, and terminates in one cycle if n = 2 of if the coordinate sets are exactly superposable, and otherwise takes a number of cycles dependent only on genuine shape differences. Enantiomorphism, if present, is detected, in which case the option exists to reverse or not to reverse the chirality of relevant coordinate sets. The method also offers a rational approach to the problem of multiple minima and has successfully identified four distinct minima in such a case. Source code, which is arranged to enable the study of the disposition of domains in multidomain structures, is available from the author. PMID- 1303745 TI - Correlation functions as a tool for protein modeling and structure analysis. AB - Proteins present unique folding structures whose conformations are determined primarily by their amino acid sequences. At present, there is no algorithm that would correlate the sequences with the structures determined by X-ray analysis or NMR. Comparative modeling of a new protein sequence based on the known structure of a functionally related protein promises to yield model structures that may provide relevant properties of the protein. To analyze the quality of a model structure, a set of correlation functions was derived from calculations on a subset of proteins from the structure database. Twenty-three highly resolved protein structures with resolutions of at least 1.7 A from various protein families were used as the primary database. The purpose of this initial work was to find highly sensitive functions (including statistical error limits for the parameters) that describe properties of "real" proteins. Each correlation described is characterized by the correlation coefficient, the parameters for linear or nonlinear regression (coefficients of the equation), standard deviation and variance, and the confidence limits describing the statistical probability for values to occur within these limits, e.g., the natural variability of the property under examination. In addition, a method was developed for creating reasonably misfolded proteins. The ability of a correlation function to discriminate between the native structure and the misfolded conformations is expressed by the reliability index, which indicates the sensitivity of a correlation function. The term correlation functions thus summarizes a variety of efforts to find a mathematical description for the properties of protein structures, for their correlation, and for their significance. PMID- 1303747 TI - Disulfide bridges in tomato pectinesterase: variations from pectinesterases of other species; conservation of possible active site segments. AB - Analysis of tomato pectinesterase by carboxymethylation, with and without reduction, shows that the enzyme has two intrachain disulfide bridges. Analysis of fragments obtained from the native enzyme after digestion with pepsin identified bridges connecting Cys-98 with Cys-125, and Cys-166 with Cys-200. The locations of disulfide bridges in tomato pectinesterase are not identical to those in three distantly related pectinesterases (18-33% residue identities) from microorganisms. However, one half-Cys (i.e., Cys-166) position is conserved in all four enzymes. Sequence comparisons of the overall structures suggest a special importance for three short segments of the entire protein. One segment is at the N-terminal part of the tomato pectinesterase, another in the C-terminal portion near the distal end of the second disulfide loop, and the third segment is located in the central part between the two disulfide bridges. The latter segment, encompassing only 40 residues of the entire protein, appears to high light a functional site in a midchain segment. PMID- 1303748 TI - Specificity mapping of cellulolytic enzymes: classification into families of structurally related proteins confirmed by biochemical analysis. AB - The specificities of 15 cellulolytic enzymes have been examined using chromophoric glycosides derived from D-glucose, cellobiose, higher cellooligosaccharides, lactose, D-xylose, and beta-(1,4)-xylobiose. Coinciding with a classification based on hydrophobic cluster analysis of amino acid sequences, six families each showing a characteristic specificity pattern were observed. Furthermore, in these cases where the anomeric forms of reaction products were determined, results seem to indicate conservation of intrinsic reaction mechanism (single or double displacement) within each family. On the other hand, the low molecular weight substrates do not discriminate exo- from endocellulases. This functional differentiation is speculated to originate from the presence, in exoenzymes, of a tunnel-shaped active site formed by extra loops in their structure. PMID- 1303749 TI - Inactivation and covalent modification of CTP synthetase by thiourea dioxide. AB - Thiourea dioxide was used in chemical modification studies to identify functionally important amino acids in Escherichia coli CTP synthetase. Incubation at pH 8.0 in the absence of substrates led to rapid, time dependent, and irreversible inactivation of the enzyme. The second-order rate constant for inactivation was 0.18 M-1 s-1. Inactivation also occurred in the absence of oxygen and in the presence of catalase, thereby ruling out mixed-function oxidation/reduction as the mode of amino acid modification. Saturating concentrations of the substrates ATP and UTP, and the allosteric activator GTP prevented inactivation by thiourea dioxide, whereas saturating concentrations of glutamine (a substrate) did not. The concentration dependence of nucleotide protection revealed cooperative behavior with respect to individual nucleotides and with respect to various combinations of nucleotides. Mixtures of nucleotides afforded greater protection against inactivation than single nucleotides alone, and a combination of the substrates ATP and UTP provided the most protection. The Hill coefficient for nucleotide protection was approximately 2 for ATP, UTP, and GTP. In the presence of 1:1 ratios of ATP:UTP, ATP:GTP, and UTP:GTP, the Hill coefficient was approximately 4 in each case. Fluorescence and circular dichroism measurements indicated that modification by thiourea dioxide causes detectable changes in the structure of the protein. Modification with [14C]thiourea dioxide demonstrated that complete inactivation correlates with incorporation of 3 mol of [14C]thiourea dioxide per mole of CTP synthetase monomer. The specificity of thiourea dioxide for lysine residues indicates that one or more lysines are most likely involved in CTP synthetase activity. The data further indicate that nucleotide binding prevents access to these functionally important residues. PMID- 1303750 TI - Unfolding domains of recombinant fusion alpha alpha-tropomyosin. AB - The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 degrees C involving the middle of the molecule; (2) a major transition at 46 degrees C involving no more than 36% of the helix from the C-terminus; (3) a major transition at 56 degrees C involving about 46% of the helix from the N-terminus; and (4) a transition from the nonhelical fusion domain at about 70 degrees C. Rabbit skeletal muscle tropomyosin, which lacks the fusion peptide but has the same tropomyosin sequence, does not exhibit the 56 degrees C or 70 degrees C transition. The very stable fusion unfolding domain of fusion-tropomyosin, which appears in electron micrographs as a globular structural domain at one end of the tropomyosin rod, acts as a cross-link to stabilize the adjacent N-terminal domain. The least stable middle of the molecule, when unfolded, acts as a boundary to allow the independent unfolding of the C-terminal domain at 46 degrees C from the stabilized N-terminal unfolding domain at 56 degrees C. Thus, strong localized interchain interactions in coiled-coil molecules can increase the stability of neighboring domains. PMID- 1303751 TI - A new subfamily of bacterial ABC-type transport systems catalyzing export of drugs and carbohydrates. AB - Sequence comparison studies revealed that the drug resistance transporter of Streptomyces peucetius (DrrAB) and two nodulation gene products (NodIJ) of Rhizobium leguminosarum are homologous to proteins encoded by three sets of genes that comprise capsular polysaccharide export systems in gram-negative bacteria: KpsTM of Escherichia coli, BexABC of Haemophilus influenzae, and CtrDCB of Neisseria meningitidis. These five systems comprise a new subfamily within the family of ATP binding cassette (ABC)-type transporters. We have termed this subfamily the ABC-2 subfamily. For three of the systems comprising this subfamily (Drr, Nod, and Kps) only one integral membrane constituent has been identified, whereas for the other two systems (Bex and Ctr) two dis-similar integral membrane constituents have been found. This observation suggests that the transmembrane channels of ABC-2-type transporters can be formed of homo- or heterooligomers as is true of several other classes of transport systems. PMID- 1303752 TI - Differences in the amino acid distributions of 3(10)-helices and alpha-helices. AB - Local determinants of 3(10)-helix stabilization have been ascertained from the analysis of the crystal structure data base. We have clustered all 5-length substructures from 51 nonhomologous proteins into classes based on the conformational similarity of their backbone dihedral angles. Several clusters, derived from 3(10)-helices and multiple-turn conformations, had strong amino acid sequence patterns not evident among alpha-helices. Aspartate occurred over twice as frequently in the N-cap position of 3(10)-helices as in the N-cap position of alpha-helices. Unlike alpha-helices, 3(10)-helices had few C-termini ending in a left-handed alpha conformation; most 3(10) C-caps adopted an extended conformation. Differences in the distribution of hydrophobic residues among 3(10) and alpha-helices were also apparent, producing amphipathic 3(10)-helices. Local interactions that stabilize 3(10)-helices can be inferred both from the strong amino acid preferences found for these short helices, as well as from the existence of substructures in which tertiary interactions replace consensus local interactions. Because the folding and unfolding of alpha-helices have been postulated to proceed through reverse-turn and 3(10)-helix intermediates, sequence differences between 3(10)- and alpha-helices can also lend insight into factors influencing alpha-helix initiation and propagation. PMID- 1303753 TI - NMR analysis of regioselectivity in dephosphorylation of a triphosphotyrosyl dodecapeptide autophosphorylation site of the insulin receptor by a catalytic fragment of LAR phosphotyrosine phosphatase. AB - An autophosphorylation site in the activated insulin receptor tyrosine kinase domain has three tyrosines phosphorylated when fully activated. To begin to examine recognition of triphosphotyrosyl sites by protein tyrosine phosphatases in possible control of signal transduction a triphosphotyrosyl dodecapeptide TRDIpYETDpYpYRK corresponding to residues 1,142-1,153 of the insulin receptor was prepared and incubated with the 40-kDa catalytic domain of the human PTPase LAR. To assess regioselectivity of recognition, the three diphosphotyrosyl regioisomers, and the three monophosphotyrosyl regioisomers were prepared and assayed. All seven peptides were PTPase substrates. To identify any preferences in dephosphorylation at pY5, pY9, or pY10, 1H-NMR analyses were conducted during enzyme incubations and distinguishing fingerprint regions determined for each of the seven phosphotyrosyl peptides. LAR PTPase shows strong preference for dephosphorylation first at pY5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the Y5(pY9)(pY10) diphospho regioisomer, followed by equal dephosphorylation at pY9 or pY10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product. The NMR methodology is applicable to other peptides with multiple sites of phosphorylation that undergo attack by any phosphatase. PMID- 1303754 TI - Solution structure of the phosphocarrier protein HPr from Bacillus subtilis by two-dimensional NMR spectroscopy. AB - The solution structure of the phosphocarrier protein, HPr, from Bacillus subtilis has been determined by analysis of two-dimensional (2D) NMR spectra acquired for the unphosphorylated form of the protein. Inverse-detected 2D (1H-15N) heteronuclear multiple quantum correlation nuclear Overhauser effect (HMQC NOESY) and homonuclear Hartmann-Hahn (HOHAHA) spectra utilizing 15N assignments (reported here) as well as previously published 1H assignments were used to identify cross-peaks that are not resolved in 2D homonuclear 1H spectra. Distance constraints derived from NOESY cross-peaks, hydrogen-bonding patterns derived from 1H-2H exchange experiments, and dihedral angle constraints derived from analysis of coupling constants were used for structure calculations using the variable target function algorithm, DIANA. The calculated models were refined by dynamical simulated annealing using the program X-PLOR. The resulting family of structures has a mean backbone rmsd of 0.63 A (N, C alpha, C', O atoms), excluding the segments containing residues 45-59 and 84-88. The structure is comprised of a four-stranded antiparallel beta-sheet with two antiparallel alpha helices on one side of the sheet. The active-site His 15 residue serves as the N cap of alpha-helix A, with its N delta 1 atom pointed toward the solvent to accept the phosphoryl group during the phosphotransfer reaction with enzyme I. The existence of a hydrogen bond between the side-chain oxygen atom of Tyr 37 and the amide proton of Ala 56 is suggested, which may account for the observed stabilization of the region that includes the beta-turn comprised of residues 37 40. If the beta alpha beta beta alpha beta (alpha) folding topology of HPr is considered with the peptide chain polarity reversed, the protein fold is identical to that described for another group of beta alpha beta beta alpha beta proteins that include acylphosphatase and the RNA-binding domains of the U1 snRNP A and hnRNP C proteins. PMID- 1303756 TI - Intron locations and functional deletions in relation to the design and evolution of a subgroup of class I tRNA synthetases. PMID- 1303755 TI - Total chemical synthesis, characterization, and immunological properties of an MHC class I model using the TASP concept for protein de novo design. AB - The design, total chemical synthesis, and immunological properties of a four alpha-helix bundle template-assembled synthetic protein (TASP) mimicking some of the structural features of the major histocompatibility complex (MHC) class I is described. In a first approach, the native sequence 58-74 of the alpha 1 heavy chain domain of HLA-A2 was modeled in order to increase helix stability and amphiphilicity of the 17-mer peptide, preserving the residues for potential T cell receptor (TcR) binding properties. According to the TASP concept, these helical segments were covalently attached to a cyclic template molecule designed for the induction of a four-helix-bundle topology of the assembled peptide blocks. After extensive HPLC purification, stepwise solid-phase synthesis resulted in a TASP molecule of high chemical purity as demonstrated by analytical HPLC, mass spectrometry, and amino acid analysis. CD spectroscopic investigations are consistent with the onset of a partial alpha-helical conformation in aqueous buffer as well as in TFE. Antibodies raised directly against this four-alpha helix bundle TASP molecule (without prior conjugation to a carrier molecule) were detected by ELISA. Flow cytometry studies showed that these antibodies recognize the native MHC class I molecule on the surface of HLA-A2-positive cells. The results indicate that the TASP approach represents a versatile tool for mimicking conformational epitopes. PMID- 1303757 TI - The origin of a useful concept--feedback inhibition. PMID- 1303758 TI - Walter Kauzmann is the recipient of the 1993 Stein and Moore Award. PMID- 1303759 TI - John Edsall and Protein Science. PMID- 1303760 TI - Issue dedicated to John Edsall on the occasion of his 90th birthday. PMID- 1303761 TI - Effects of DNA binding and metal substitution on the dynamics of the GAL4 DNA binding domain as studied by amide proton exchange. AB - Backbone amide proton exchange rates in the DNA-binding domain of GAL4 have been determined using 1H-15N heteronuclear correlation NMR spectroscopy. Three forms of the protein were studied-the native Zn-containing protein, the Cd-substituted protein, and a Zn-GAL4/DNA complex. Exchange rates in the Zn-containing protein are significantly slower than in the Cd-substituted protein. This shows that Cd substituted GAL4 is destabilized relative to the native Zn-containing protein. Upon DNA binding, global retardation of amide proton exchange with solvent was observed, indicating that internal fluctuations of the DNA-recognition module are significantly reduced by the presence of DNA. In all forms of the protein, the internal dyad symmetry of the DNA-recognition module of GAL4 is reflected by the backbone amide proton exchange rates. PMID- 1303762 TI - Structure of the oxidized long-chain flavodoxin from Anabaena 7120 at 2 A resolution. AB - The structure of the long-chain flavodoxin from the photosynthetic cyanobacterium Anabaena 7120 has been determined at 2 A resolution by the molecular replacement method using the atomic coordinates of the long-chain flavodoxin from Anacystis nidulans. The structure of a third long-chain flavodoxin from Chondrus crispus has recently been reported. Crystals of oxidized A. 7120 flavodoxin belong to the monoclinic space group P2(1) with a = 48.0, b = 32.0, c = 51.6 A, and beta = 92 degrees, and one molecule in the asymmetric unit. The 2 A intensity data were collected with oscillation films at the CHESS synchrotron source and processed to yield 9,795 independent intensities with Rmerg of 0.07. Of these, 8,493 reflections had I > 2 sigma and were used in the analysis. The model obtained by molecular replacement was initially refined by simulated annealing using the XPLOR program. Repeated refitting into omit maps and several rounds of conjugate gradient refinement led to an R-value of 0.185 for a model containing atoms for protein residues 2-169, flavin mononucleotide (FMN), and 104 solvent molecules. The FMN shows many interactions with the protein with the isoalloxazine ring, ribityl sugar, and the 5'-phosphate. The flavin ring has its pyrimidine end buried into the protein, and the functional dimethyl benzene edge is accessible to solvent. The FMN interactions in all three long-chain structures are similar except for the O4' of the ribityl chain, which interacts with the hydroxyl group of Thr 88 side chain in A. 7120, while with a water molecule in the other two. The phosphate group interacts with the atoms of the 9-15 loop as well as with NE1 of Trp 57. The N5 atom of flavin interacts with the amide NH of Ile 59 in A. 7120, whereas in A. nidulans it interacts with the amide NH of Val 59 in a similar manner. In C. crispus flavodoxin, N5 forms a hydrogen bond with the side chain hydroxyl group of the equivalent Thr 58. The hydrogen bond distances to the backbone NH groups in the first two flavodoxins are 3.6 A and 3.5 A, respectively, whereas in the third flavodoxin the distance is 3.1 A, close to the normal value. Even though the hydrogen bond distances are long in the first two cases, still they might have significant energy because their microenvironment in the protein is not accessible to solvent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1303763 TI - Arginine 54 in the active site of Escherichia coli aspartate transcarbamoylase is critical for catalysis: a site-specific mutagenesis, NMR, and X-ray crystallographic study. AB - The replacement of Arg-54 by Ala in the active site of Escherichia coli aspartate transcarbamoylase causes a 17,000-fold loss of activity but does not significantly influence the binding of substrates or substrate analogs (Stebbins, J.W., Xu, W., & Kantrowitz, E.R., 1989, Biochemistry 28, 2592-2600). In the X-ray structure of the wild-type enzyme, Arg-54 interacts with both the anhydride oxygen and a phosphate oxygen of carbamoyl phosphate (CP) (Gouaux, J.E. & Lipscomb, W.N., 1988, Proc. Natl. Acad. Sci. USA 85, 4205-4208). The Arg-54-->Ala enzyme was crystallized in the presence of the transition state analog N phosphonacetyl-L-aspartate (PALA), data were collected to a resolution limit of 2.8 A, and the structure was solved by molecular replacement. The analysis of the refined structure (R factor = 0.18) indicates that the substitution did not cause any significant alterations to the active site, except that the side chain of the arginine was replaced by two water molecules. 31P-NMR studies indicate that the binding of CP to the wild-type catalytic subunit produces an upfield chemical shift that cannot reflect a significant change in the ionization state of the CP but rather indicates that there are perturbations in the electronic environment around the phosphate moiety when CP binds to the enzyme. The pH dependence of this upfield shift for bound CP indicates that the catalytic subunit undergoes a conformational change with a pKa approximately 7.7 upon CP binding. Furthermore, the linewidth of the 31P signal of CP bound to the Arg-54-->Ala enzyme is significantly narrower than that of CP bound to the wild-type catalytic subunit at any pH, although the change in chemical shift for the CP bound to the mutant enzyme is unaltered. 31P-NMR studies of PALA complexed to the wild-type catalytic subunit indicate that the phosphonate group of the bound PALA exists as the dianion at pH 7.0 and 8.8, whereas in the Arg-54-->Ala catalytic subunit the phosphonate group of the bound PALA exists as the monoanion at pH 7.0 and 8.8. Thus, the side chain of Arg-54 is essential for the proper ionization of the phosphonate group of PALA and by analogy the phosphate group in the transition state. These data support the previously proposed proton transfer mechanism, in which a fully ionized phosphate group in the transition state accepts a proton during catalysis. PMID- 1303764 TI - A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41. AB - The mechanism of protein-mediated membrane fusion and lysis has been investigated by solution-state studies of the effects of peptides on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41) of the human immunodeficiency virus (HIV) was synthesized and tested for its ability to cause lipid membranes to fuse together (fusion) or to break open (lysis). These effects were compared to those produced by the lytic and fusogenic peptide from bee venom, melittin. Other properties studied included the changes in visible absorbance and mean particle size, and the secondary structure of peptides as judged by CD spectroscopy. Taken together, the observations suggest that protein-mediated membrane fusion is dependent not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form an amphiphilic structure that promotes the mixing of the lipids between membranes. A speculative molecular model is proposed for membrane fusion by alpha-helical peptides, and its relationship to the forces involved in protein-membrane interactions is discussed. PMID- 1303765 TI - Modeling the antigen combining site of an anti-dinitrophenyl antibody, ANO2. AB - A model structure has been constructed for a monoclonal anti-dinitrophenyl antibody. The antibody, ANO2, has been sequenced and cloned (Anglister, J., Frey, T., & McConnell, H.M., 1984, Biochemistry 23, 1138-1142). Its amino acid sequence shows striking homology with the anti-lysozyme Fab fragments HyHel5 (83%) and HyHel10 (73%). Based on this homology, a model for the ANO2 variable heavy and variable light chain framework was constructed using a hybrid of the HyHel5 light chain and the HyHel10 heavy chain backbone, omitting the hypervariable loops. These coordinates were used as scaffolds for the model building of ANO2. The CONGEN conformational sampling algorithm (Bruccoleri, R.E. & Karplus, M., 1987, Biopolymers 26, 127-196) was used to model the six hypervariable loops that contain the antigen-combining site. All the possible conformations of the loop backbones were constructed and the best loop structures were selected using a combination of the CHARMM potential energy function and evaluation of the solvent accessible surface area of the conformers. The order in which the loops were searched was carried out based on the relative locations of the loops with reference to the framework of the beta-barrel, namely, L2-H1-L3-H2-H3-L1. The model structures thus obtained were compared to the high resolution X-ray structure (Brunger, A.T., Leahy, D.J., Hynes, T.R., & Fox, R.O., 1991, J. Mol. Biol. 221, 239-256). PMID- 1303766 TI - Conformational stability of porcine serum transferrin. AB - The conformation of porcine serum ferric transferrin (Tf) and its stability against denaturation were studied by circular dichroism. Tf was estimated to have 19-24% alpha-helix and 50-55% beta-sheet based on the methods of Chang et al. (Chang, C.T., Wu, C.-S.C., & Yang, J.T., 1978, Anal. Biochem. 91, 13-31) and Provencher and Glockner (Provencher, S.W. & Glockner, J., 1981, Biochemistry 20, 33-37). Removal of the bound ferric ions (apo-Tf) did not alter the overall conformation, but there were subtle changes in local conformation based on its near-UV CD spectrum. The Tfs were stable between pH 3.5 and 11. Denaturation by guanidine hydrochloride (Gu-HCl) showed two transitions at 1.6 and 3.4 M denaturant. The process of denaturation by acid and base was reversible, whereas that by Gu-HCl was partially reversible. The irreversible thermal unfolding of Tfs began at temperatures above 60 degrees C and was not complete even at 80 degrees C. The bound irons (based on absorbance at 460 nm) were completely released at pH < 4 or in Gu-HCl solution above 1.7 M, when the protein began to unfold, but they remained intact in neutral solution even at 85 degrees C. The NH2- and COOH-terminal halves of the Tf molecule obtained by limited trypsin digestion had CD spectra similar to the spectrum of native Tf, and the COOH terminal fragment had more stable secondary structure than the NH2-terminal fragment. PMID- 1303767 TI - Kinetic studies of the refolding of yeast phosphoglycerate kinase: comparison with the isolated engineered domains. AB - Unfolding and refolding kinetics of yeast phosphoglycerate kinase were studied by following the time-dependent changes of two signals: the ellipticity at 218 nm and 222 nm, and the fluorescence emission at 330 nm (following excitation at 295 nm). The protein is composed of two similar-sized structural domains. Each domain has been produced by recombinant DNA techniques. It has been previously demonstrated that the engineered isolated domains are able to fold into a quasinative structure (Minard, P., et al., 1989b, Protein Eng. 3, 55-60; Missiakas, D., Betton, J.M., Minard, P., & Yon, J.M., 1990, Biochemistry 29, 8683 8689). The behavior of the isolated domains was studied using the same two conformational probes as for the whole enzyme. We found that the refolding kinetics of each domain are multiphasic. In the whole protein, domain folding and pairing appeared to be simultaneous events. However, it was found that some refolding steps occurring during the refolding of the isolated C-domain are masked during the refolding of yeast phosphoglycerate kinase. The N-domain was also found to refold faster when it was isolated than when integrated. PMID- 1303769 TI - Solution-state structure by NMR of zinc-substituted rubredoxin from the marine hyperthermophilic archaebacterium Pyrococcus furiosus. AB - The three-dimensional solution-state structure is reported for the zinc substituted form of rubredoxin (Rd) from the marine hyperthermophilic archaebacterium Pyrococcus furiosus, an organism that grows optimally at 100 degrees C. Structures were generated with DSPACE by a hybrid distance geometry (DG)-based simulated annealing (SA) approach that employed 403 nuclear Overhauser effect (NOE)-derived interproton distance restraints, including 67 interresidue, 124 sequential (i-j = 1), 75 medium-range (i-j = 2-5), and 137 long-range (i-j > 5) restraints. All lower interproton distance bounds were set at the sum of the van Der Waals radii (1.8 A), and upper bounds of 2.7 A, 3.3 A, and 5.0 A were employed to represent qualitatively observed strong, medium, and weak NOE cross peak intensities, respectively. Twenty-three backbone-backbone, six backbone sulfur (Cys), two backbone-side chain, and two side chain-side chain hydrogen bond restraints were include for structure refinement, yielding a total of 436 nonbonded restraints, which averages to > 16 restraints per residue. A total of 10 structures generated from random atom positions and 30 structures generated by molecular replacement using the backbone coordinates of Clostridium pasteurianum Rd converged to a common conformation, with the average penalty (= sum of the square of the distance bounds violations; +/- standard deviation) of 0.024 +/- 0.003 A2 and a maximum total penalty of 0.035 A2. Superposition of the backbone atoms (C, C alpha, N) of residues A1-L51 for all 40 structures afforded an average pairwise root mean square (rms) deviation value (+/- SD) of 0.42 +/- 0.07 A. Superposition of all heavy atoms for residues A1-L51, including those of structurally undefined external side chains, afforded an average pairwise rms deviation of 0.72 +/- 0.08 A. Qualitative comparison of back-calculated and experimental two-dimensional NOESY spectra indicate that the DG/SA structures are consistent with the experimental spectra. The global folding of P. furiosus Zn(Rd) is remarkably similar to the folding observed by X-ray crystallography for native Rd from the mesophilic organism C. pasteurianum, with the average rms deviation value for backbone atoms of residues A1-L51 of P. furiosus Zn(Rd) superposed with respect to residues K2-V52 of C. pasteurianum Rd of 0.77 +/- 0.06 A. The conformations of aromatic residues that compose the hydrophobic cores of the two proteins are also similar. However, P. furiosus Rd contains several unique structural elements, including at least four additional hydrogen bonds and three potential electrostatic interactions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1303770 TI - Comparison of the X-ray structure of native rubredoxin from Pyrococcus furiosus with the NMR structure of the zinc-substituted protein. AB - The three-dimensional X-ray structures of the oxidized and reduced forms of rubredoxin from Pyrococcus furiosus, determined at -161 degrees C, and the NMR structure of the zinc-substituted protein, determined in solution at 45 degrees C, are compared. The NMR and X-ray structures, which were determined independently, are very similar and lead to similar conclusions regarding the interactions that confer hyperthermostability. PMID- 1303768 TI - X-ray crystal structures of the oxidized and reduced forms of the rubredoxin from the marine hyperthermophilic archaebacterium Pyrococcus furiosus. AB - The structures of the oxidized and reduced forms of the rubredoxin from the archaebacterium, Pyrococcus furiosus, an organism that grows optimally at 100 degrees C, have been determined by X-ray crystallography to a resolution of 1.8 A. Crystals of this rubredoxin grow in space group P2(1)2(1)2(1) with room temperature cell dimensions a = 34.6 A, b = 35.5 A, and c = 44.4 A. Initial phases were determined by the method of molecular replacement using the oxidized form of the rubredoxin from the mesophilic eubacterium, Clostridium pasteurianum, as a starting model. The oxidized and reduced models of P. furiosus rubredoxin each contain 414 nonhydrogen protein atoms comprising 53 residues. The model of the oxidized form contains 61 solvent H2O oxygen atoms and has been refined with X-PLOR and TNT to a final R = 0.178 with root mean square (rms) deviations from ideality in bond distances and bond angles of 0.014 A and 2.06 degrees, respectively. The model of the reduced form contains 37 solvent H2O oxygen atoms and has been refined to R = 0.193 with rms deviations from ideality in bond lengths of 0.012 A and in bond angles of 1.95 degrees. The overall structure of P. furiosus rubredoxin is similar to the structures of mesophilic rubredoxins, with the exception of a more extensive hydrogen-bonding network in the beta-sheet region and multiple electrostatic interactions (salt bridge, hydrogen bonds) of the Glu 14 side chain with groups on three other residues (the amino-terminal nitrogen of Ala 1; the indole nitrogen of Trp 3; and the amide nitrogen group of Phe 29). The influence of these and other features upon the thermostability of the P. furiosus protein is discussed. PMID- 1303771 TI - Memories of early days in protein science, 1926-1940. PMID- 1303772 TI - [Effect of loratadine--selective antagonist of histamine (H1) receptor--on allergen-induced bronchoconstriction in atopic asthmatics]. AB - The aim of this study was to evaluate the effect of loratadine on allergen induced bronchoconstriction. The study was performed in 7 asthmatic patients with sensitivity to Dermatophagoides pteronyssinus, 4 women and 3 men. aged from 19 to 37 years. The allergen inhalatory--challenge test was performed according to Chai et al. Early phase of Dermatophagoides pteronyssinus--induced bronchoconstriction appeared in all examined patients, but late phase of bronchial obstruction was observed only in 3 persons. 30 mg orally administered of loratadine have no protect effect on early phase of allergen--induced bronchoconstriction. After loratadine ingestion the late phase of this bronchial obstruction disappeared. PMID- 1303773 TI - [Effect of loratadine (LO), a selective H1 antagonist, on histamine-induced bronchoconstriction]. AB - The influence of single and repeated LO (10 mg/day) doses on histamine-induced bronchoconstriction was studied in 11 patients with stabile bronchial asthma. Bronchial reactivity was estimated as histamine content potent to elicit a 20% FEV, fall, i.e. PC20H. A single dose gave a significant (5.5 fold) reduction in bronchial reactivity to inhaled histamine. Application of LO during 6 days gave a similar effect. Withdrawal of LO for 6 days yielded an increase in bronchial hyperreactivity. PMID- 1303774 TI - [Effect of cetirizine, selective H1 antagonist of histamine on skin and bronchial reactivity and cellular histamine release in allergic diseases]. AB - The study aimed at evaluating an effect of cetirizine--selective antagonist of histamine H1 receptor--on skin and bronchial reaction to histamine, and histamine release from the cells by pollen antigen and anti-IgE. Skin reactivity was tested thrice in 33 patients treated with Zyrtec (Polfa) for the chronic urticaria or allergic rhinitis. Reaction of the bronchi to histamine was tested with a technique described by Ryan et al in 10 asthmatic patients. As effect of cetirizine on histamine release from neutrophils was evaluated in patients with pollinosis before and on the fourth day of therapy. It was shown that the treatment with Zyrtec markedly decreases skin reaction to histamine. Single dose of drug administered 4 hours before the tests markedly restricts reactivity of the bronchi. Daily dose of 10 mg administered to patients with pollinosis stabilizes membranes of neutrophils. PMID- 1303775 TI - [Cetirizine for treating allergic seasonal rhinitis]. AB - In 14 persons suffering from allergic, seasonal rhinitis the efficacy of 14-days treatment of cetirizine (Zyrtec 10 mg/day) was evaluated. The study was performed in double blind randomised method. Cetirizine was significantly more effective than placebo in reducing the clinical symptoms of rhinitis near in 60% patients. The improvement of nasal mucosa state in laryngological investigation was observed in patients who were better clinically. The inhalatory challenge test with histamine in 9 patients was positive and after cetirizine treatment the bronchial hyperreactivity disappeared. PMID- 1303776 TI - [The effect of muscarinic receptor blockers on non-specific bronchial reactivity in patients with bronchial asthma]. AB - The effect of two anticholinergic drugs, Ipratropium bromide, nonselective muscarinic receptor antagonist and Pirenzepine, a selective M1 receptor blocker on bronchospasm induced by metacholine and histamine was investigated. The studies were carried out in a group of 52 asthmatic patients. The provocation tests were made by the Ryan method using a De Vilbiss nebuliser connected to a Rosenthal-French dosimeter. It was shown that both drugs protect significantly metacholine induced bronchospasm, but Ipratropium was more effective than Pirenzepine, which suggest that blockade of the M1 receptors only is not sufficient for a complete limitation of bronchi response to metacholine challenge. After histamine provocation some limitation of bronchial reactivity by two investigated drugs was also observed, but not so marked as after metacholine provocation. No significant differences between the effects of Pirenzepine and Ipratropium on histamine induced bronchospasm were observed. PMID- 1303777 TI - [Late effort induced asthmatic response in patients with atopic bronchial asthma after administration of cromoglycate disodium with concurrent evaluation of neutrophil chemotactic factor (NCG) in serum]. AB - To evaluate an effect of Intal on the late post-provocation bronchospasm in 30 patients with atopic asthma (with early bronchospasm) the treatment was accompanied by the assessment of NCF activity (as a marker of mastocytes degranulation. It was shown that after therapy with Intal exerted an effect on the NCF activity not only in the early but also late bronchospasm in comparison with its activity in patients after exercise test but prior to therapy--9/22 and 6/29. The authors share an opinion tha the presence of NCF in part of patients with the late postexercise bronchospasm (treated with Intal) may indicate that its origin is different (not from mastocytes). PMID- 1303778 TI - [Clinical evaluation of procaterol and salbutamol in patients with bronchial asthma]. AB - When the beta-2-selectivity of beta-agonists is assessed in man it is always considerably less than would be expected from studies on isolated tissues. That was a reason why this study was taken. As we know procaterol has been included into group of beta-2-selective non-catecholamines with a reasonably long duration of action. We performed clinical evaluation of procaterol and salbutamol on 24 patients with bronchial asthma. Procaterol was administered per os (tabl. a 50 micrograms twice daily) during 4 weeks, and next salbutamol was replaced above mentioned (tabl. a 8 mg twice daily) also during 4 weeks. Clinical symptoms and spirometric values were analyzed. Obtained results indicated that procaterol and salbutamol showed a similar potency in spirometric examination in patients with bronchial asthma. Observed side effects after procaterol were less often than after salbutamol. PMID- 1303779 TI - [On the late post-provocation spasm of the bronchi]. AB - To assess the incidence of the late reaction of the bronchi in patients with atopic asthma the following methods of the provocation with atopic asthma the following methods of the provocation were applied: a) exercise test, b) a 3 minute ventilation with cold air and c) inhalation of the distilled water Disturbances of ventilation were assessed spirographically. An emphasis was also on the activity of NCF in the blood serum following the applied provocation tests. It was found that the late bronchospasm followed the exercise test in about half of the examined patients (48%). It was less frequent after hyperventilation with cold air (33%) and inhalation of the distilled water (38%). Bronchospasm was accompanied by the increase in NCF activity in the blood serum. The late bronchospasm after provocation tests in asthmatics is a real fact, not depending on the accidental ventilation disorders. PMID- 1303780 TI - [Effect of cyclosporine A on the clinical state and spirometric parameters in patients with steroid-dependent bronchial asthma]. AB - The study aimed at assessing an effect of Cs A on spirometric indices in 30 patients with steroid-dependent bronchial asthma. All patients were treated with triamcinolone in a mean daily dose of 6-8 mg for at least 5 years. Half of patients were given in a double blind trial cyclosporin in a daily dose of 100 mg for 2 years. The remaining 15 patients were not given cyclosporin. All patients were also given corticosteroids, methylxanthines, and mucolytics. Statistically significant increase in FVC, FEV1, and PEFR was noted in patients treated with cyclosporin after 2 years while no change was seen in patients not given Cs. At the same time, a reduction of corticoids doses and diminished of post-steroid symptoms were noted in patients treated with cyclosporin. PMID- 1303781 TI - [The effect of peat preparation on the release of histamine from basophils of atopic bronchial asthma]. AB - Antigen-induced basophil histamine releasing (BHR) is an in vitro model of the immediate-type allergic reaction. We studied the influence of immunologically active peat preparation (PTT). On BHR induced with specific antigen or Con A. The highest concentration of PTT enhanced, but lower concentrations decreased antigen induced BHR. Surprisingly, similar effect was observed with placebo, suggestions that immunologically inactive components of both preparations may be responsible for the modulatory activity. PMID- 1303782 TI - [Effect of long term systemic steroid therapy on the cardiac muscle]. AB - In asthmatic patients treated on a long term basis with steroids echocardiographic examination of the heart disclosed morphological and functional changes in the heart muscle. Such changes were not found in asthmatic treated occasionally with steroids. Differences between both groups depended on decreased contractibility of the heart muscle and concentric hypertrophy of the left ventricle present in asthmatic treated on a long term basis with systemic steroids. PMID- 1303783 TI - [Paradoxic bronchial constriction after inhalation of fenoterol and ipratropium bromide]. AB - Two cases of paradoxic bronchial constriction after inhalation of fenoterol and ipratropium bromide are presented. Both patients had bronchial asthma. In the first case the inhalation of fenoterol produced dyspnea and a decrease of FEV1 and FEF25-75. In the second similar observations were made after inhalation of ipratropium bromide. The above mentioned observations illustrate the risk of drug related paradoxic reactions, especially in atopic patients. PMID- 1303784 TI - [Pulmonary tuberculosis in a man infected with HIV]. PMID- 1303785 TI - [Inhalation administration of diuretics in patients with bronchial asthma]. PMID- 1303786 TI - [Intravenous immunoglobulins--new method of diminishing corticosteroid dependency of asthma]. PMID- 1303787 TI - [The SmithKline Beecham Awards, 1989-1991]. PMID- 1303788 TI - [Academic eulogy of Professor Gaston Lagrange, native honorary member]. PMID- 1303789 TI - [Clinical and biochemical correlations in certain metabolic myopathies]. AB - Muscular glycogenosis is a disease resulting from genetical abnormalities altering an enzyme which is involved in glycogen metabolism. In addition to disorders of glycogenosis and glycolysis, there are other pathological processes such as alpha-glycosidase deficiency and diseases associated with abnormal polysaccharide structure. A short review of the various diseases with their particular features is reported. PMID- 1303790 TI - [Regulation of kidney hemodynamics. Role of endothelial factors]. AB - The vascular endothelium produces relaxing (PGI2 and EDRF) and contracting (endothelin) factors of the vascular smooth muscle cells. Among these, EDRF, recently identified as NO, is most important. Indeed, NO is continuously formed in the endothelial cells and can thus maintain a state of active and permanent vasodilatation. Consequently, NO may also set the systemic arterial pressure. Our experimental observations suggest that NO sets approximately 50% of the vasomotor tone of the arterial circulation including the renal circulation. In this regard, the activity of NO is not indispensable to renal blood flow autoregulation. Alterations of NO's and/or other endothelial factors' synthesis occur in a variety of cardio-vascular and renal diseases. A better understanding of the physiology and pathophysiology of the vascular endothelium will certainly allow to consider new and exciting therapeutic perspectives in these areas. PMID- 1303791 TI - The early nodulin gene SrEnod2 from Sesbania rostrata is inducible by cytokinin. AB - The structure and expression of the early nodulin gene Enod2 from the stem nodulated tropical legume Sesbania rostrata (SrEnod2) was examined. Genomic clones carrying the single SrEnod2locus were isolated and the DNA sequence of the gene was determined. The SrEnod2 gene was found to lack introns and to encode a protein consisting primarily of a 55-fold repeat of short proline-rich oligopeptides. A putative signal sequence, which may be responsible for targeting of the Enod2 protein to the cell wall, was found to precede this repeat. The temporal expression of the SrEnod2 gene was found to be different in S. rostrata stem versus root nodules induced by Azorhizobium caulinodans ORS571. SrEnod2 gene expression was shown to be induced specifically and rapidly by physiologically significant concentrations of exogenously supplied cytokinins. The SrEnod2 gene was also found to be highly expressed in S. rostrata crown gall tumors induced by wild-type Agrobacterium tumefaciens strains, but not in tumors induced by an A. tumefaciens strain carrying a mutation in the cytokinin biosynthesis gene 4. Implications of these observations with regard to cytokinin-induced plant gene expression and a possible role for cytokinin as a symbiotic signal are discussed. PMID- 1303792 TI - Molecular characterization of glutathione reductase cDNAs from pea (Pisum sativum L.). AB - A cDNA for pea glutathione reductase has been cloned and sequenced. The derived amino acid sequence of 562 residues shows a high degree of homology to the previously published GR sequences from human erythrocytes and from two prokaryotes: Escherichia coli and Pseudomonas aeruginosa. The pea enzyme differs from other GRs in having an N-terminal leader sequence of about 60-70 residues which may be a chloroplast transit peptide and a 20 amino acid C-terminal extension of unknown function. PMID- 1303793 TI - Analysis of large DNA from soybean (Glycine max L. Merr.) by pulsed-field gel electrophoresis. AB - The technique of pulsed-field gel electrophoresis (PFE) has been used to study chromosomal regions and entire genomes of several organisms. Techniques are presented for the isolation of high molecular weight DNA from embedded soybean protoplasts and the conditions for separating large DNA fragments using PFE. Digestion was detected by Southern hybridization using single copy nodulin clones. These data are being used to generate a physical map of the nodulin region(s) of the soybean genome. PMID- 1303794 TI - Identification of a cDNA for the plastid-located geranylgeranyl pyrophosphate synthase from Capsicum annuum: correlative increase in enzyme activity and transcript level during fruit ripening. AB - Geranylgeranyl pyrophosphate synthase is a key enzyme in plant terpenoid biosynthesis. Using specific antibodies, a cDNA encoding geranylgeranyl pyrophosphate synthase has been isolated from bell pepper (Capsicum annuum) ripening fruit. The cloned cDNA codes for a high molecular weight precursor of 369 amino acids which contains a transit peptide of approximately 60 amino acids. In-situ immunolocalization experiments have demonstrated that geranylgeranyl pyrophosphate synthase is located exclusively in the plastids. Expression of the cloned cDNA in E. coli has unambiguously demonstrated that the encoded polypeptide catalyzes the synthesis of geranylgeranyl pyrophosphate by the addition of isopentenyl pyrophosphate to an allylic pyrophosphate. Peptide sequence comparisons revealed significant similarity between the sequences of the C. annuum geranylgeranyl pyrophosphate synthase and those deduced from carotenoid biosynthesis (crtE) genes from photosynthetic and non-photosynthetic bacteria. In addition, four highly conserved regions, which are found in various prenyltransferases, were identified. Furthermore, evidence is provided suggesting that conserved and exposed carboxylates are directly involved in the catalytic mechanism. Finally, the expression of the geranylgeranyl pyrophosphate synthase gene is demonstrated to be strongly induced during the chloroplast to chromoplast transition which occurs in ripening fruits, and is correlated with an increase in enzyme activity. PMID- 1303795 TI - Molecular characterization and expression of an alfalfa protein with sequence similarity to mammalian ERp72, a glucose-regulated endoplasmic reticulum protein containing active site sequences of protein disulphide isomerase. AB - A complementary DNA clone (G1) containing sequence similarity to the mammalian lumenal endoplasmic reticulum protein ERp72 was isolated from an alfalfa (Medicago sativa L.) cDNA library by screening with a cDNA encoding human protein disulphide isomerase (PDI), which contains two thioredoxin-like active site regions which are highly conserved in ERp72. The polypeptide encoded by G1 consists of 364 amino acids, possesses a putative N-terminal secretory signal sequence and two regions, 113 amino acids apart, identical to the active sites of PDI and ERp72. G1 appears to be encoded by a small gene family in alfalfa, whose transcripts are constitutively expressed in all major organs of the plant. In alfalfa cell suspension cultures, G1 transcripts were markedly induced by treatment with tunicamycin, but not in response to calcium ionophore, heat shock or fungal elicitor. A similar expression pattern was observed for transcripts encoded by B2, a recently cloned alfalfa cDNA with strong sequence similarity to PDI. We discuss potential roles of plant proteins resembling vertebrate PDI and ERp72. PMID- 1303796 TI - A 126 bp fragment of a plant histone gene promoter confers preferential expression in meristems of transgenic Arabidopsis. AB - The tissue-specific pattern of expression directed by the H4A748 Arabidopsis histone promoter was investigated by analysis of beta-glucuronidase (GUS) activity in transgenic Arabidopsis containing H4A748-GUS gene fusions. As determined by fluorimetric and histochemical tests, the H4A748 promoter directs preferential expression in meristems of young seedlings and adult plants. The low activity found in nonproliferating tissues may relate to basal constitutive expression of the histone promoter and/or to endoreduplication occurring in some tissues. The endogenous histone mRNA levels parallel the GUS activity found in different tissues. Analysis of the regulatory properties of 5' deleted promoters showed that multiple positive elements exist between -900 and -219 and that the proximal region of the promoter to -219 is sufficient to establish the full tissue-specific pattern of expression. Further deletion to -93 nearly abolished the promoter activity thus suggesting that the 126 bp fragment located between 219 and -93 contains the elements responsible for the specific expression pattern. The presence of several remarkable sequences within this fragment is discussed. PMID- 1303797 TI - Characterization of DNA sequences that mediate nuclear protein binding to the regulatory region of the Pisum sativum (pea) chlorophyl a/b binding protein gene AB80: identification of a repeated heptamer motif. AB - Two protein factors binding to the regulatory region of the pea chlorophyl a/b binding protein gene AB80 have been identified. One of these factors is found only in green tissue but not in etiolated or root tissue. The second factor (denominated ABF-2) binds to a DNA sequence element that contains a direct heptamer repeat TCTCAAA. It was found that presence of both of the repeats is essential for binding. ABF-2 is present in both green and etiolated tissue and in roots and factors analogous to ABF-2 are present in several plant species. Computer analysis showed that the TCTCAAA motif is present in the regulatory region of several plant genes. PMID- 1303798 TI - Members of the acetohydroxyacid synthase multigene family of Brassica napus have divergent patterns of expression. AB - Brassica species possess the most complex acetohydroxyacid synthase (AHAS) multigene family reported for plants. The AHAS genes code for an essential enzyme in branched-chain amino acid biosynthesis. In the allotetraploid species, B. napus, four (AHAS1-4) of the five AHAS genes have been cloned and sequenced. The transcripts were examined by RNase protection assays using gene-specific, antisense RNA probes. Only AHAS1, AHAS2 and AHAS3 were shown to be expressed in B. napus and one of the diploid progenitor species B. campestris or B. oleracea. AHAS1 and AHAS3 are highly conserved genes that presumably code for the essential AHAS housekeeping functions. They were expressed as low abundance mRNA in all somatic and reproductive tissues examined. AHAS2, which is structurally distinct from all other plant AHAS genes, was only expressed in mature ovules and extraembryonic tissues of immature seeds. This study provides direct evidence for multiple AHAS isoforms in plants and for an AHAS gene which is developmentally regulated in a tissue-specific manner. The discovery raises questions concerning the functional significance of AHAS in seed development. PMID- 1303799 TI - A Brassica napus gene family which shows sequence similarity to ascorbate oxidase is expressed in developing pollen. Molecular characterization and analysis of promoter activity in transgenic tobacco plants. AB - The genomic clone named Bp10 contains a member of a small pollen-specific gene family of B. napus. The expression of the Bp10 gene family is maximal in early binucleate microspores and declines considerably in mature trinucleate pollen. Homologues of the Bp10 genes are expressed in the pollen of other plant species. The pollen-specific expression of the gene contained in the genomic clone was confirmed in tobacco plants transformed with a chimeric Bp10 promoter/GUS construct. A promoter fragment of 396 bp is sufficient to direct a strong and correct spatial and temporal expression in transgenic plants. The Bp10 gene family codes for proteins of 62 kDa showing approximately 30% sequence identify to cucumber and pumpkin ascorbate oxidases (AAOs). However, the AAO active centres are not conserved in the Bp10 products, suggesting an evolutionary relationship but a different enzymatic activity for these proteins. Expression of a recombinant Bp10 protein in E. coli inhibits bacterial growth on minimal medium, suggesting the production of an enzymatically active polypeptide in bacteria. No AAO activity could be correlated with the expression of the recombinant protein. Moreover, substances affecting AAO activity do not appear to influence the inhibitory activity of the protein produced in bacteria. However, as indicated by the rescue of bacterial growth in the presence of sodium bicarbonate or gaseous CO2, the Bp10 protein activity could be modulated by CO2 levels. PMID- 1303800 TI - Molecular analysis of the avirulence gene avr9 of the fungal tomato pathogen Cladosporium fulvum fully supports the gene-for-gene hypothesis. AB - The interaction between the fungal pathogen Cladosporium fulvum and tomato is supposed to have a gene-for-gene basis. Races of C. fulvum which have 'overcome' the resistance gene Cf9 of tomato, lack the avirulence gene avr9 which encodes a race-specific peptide elicitor. Races avirulent on tomato genotypes carrying the resistance gene Cf9 produce the race-specific peptide elicitor, which induces the hypersensitive response (HR) on those genotypes. The causal relationship between the presence of a functional avr9 gene and avirulence on tomato genotype Cf9 was demonstrated by cloning of the avr9 gene and subsequent transformation of C. fulvum. A race virulent on tomato genotype Cf9 was shown to become avirulent by transformation with the cloned avr9 gene. These results clearly demonstrate that the avr9 gene is responsible for cultivar specificity on tomato genotype Cf9 and fully support the gene-for-gene hypothesis. The avr9 gene is the first fungal avirulence gene to be cloned. PMID- 1303801 TI - Cloning and characterization of the gene encoding the endopolygalacturonase inhibiting protein (PGIP) of Phaseolus vulgaris L. AB - Polygalacturonase-inhibiting protein (PGIP) is a cell wall protein purified from hypocotyls of true bean (Phaseolus vulgaris L.). PGIP inhibits fungal endopolygalacturonases and is considered to be an important factor for plant resistance to phytopathogenic fungi (Albersheim and Anderson, 1971; Cervone et al., 1987). The amino acid sequences of the N-terminus and one internal tryptic peptide of the PGIP purified from P. vulgaris cv. Pinto were used to design redundant oligonucleotides that were successfully utilized as primers in a polymerase chain reaction (PCR) with total DNA of P. vulgaris as a template. A DNA band of 758 bp (a specific PCR amplification product of part of the gene coding for PGIP) was isolated and cloned. By using the 758-bp DNA as a hybridization probe, a lambda clone containing the PGIP gene was isolated from a genomic library of P. vulgaris cv. Saxa. The coding and immediate flanking regions of the PGIP gene, contained on a subcloned 3.3 kb SalI-SalI DNA fragment, were sequenced. A single, continuous ORF of 1026 nt (342 amino acids) was present in the genomic clone. The nucleotide and deduced amino acid sequences of the PGIP gene showed no significant similarity with any known databank sequence. Northern blotting analysis of poly(A)+ RNAs, isolated from various tissues of bean seedlings or from suspension-cultured bean cells, were also performed using the cloned PCR-generated DNA as a probe. A 1.2 kb transcript was detected in suspension-cultured cells and, to a lesser extent, in leaves, hypocotyls, and flowers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303802 TI - Stringent repression and homogeneous de-repression by tetracycline of a modified CaMV 35S promoter in intact transgenic tobacco plants. AB - A cauliflower mosaic virus (CaMV) 35S promoter derivative, which is tightly repressed by the Tn 10 encoded Tet repressor in a transient expression system as well as in transgenic plants has been constructed. After treatment of transgenic plants with tetracycline (Tc) the activity of the reporter enzyme beta glucuronidase (GUS) increased up to 500-fold in tissue culture as well as under greenhouse conditions. Efficient de-repression was achieved by Tc uptake through the roots as well as by Tc treatment of leaves of intact plants. As Tc is not very stable in the plants, this system can also be used for a transient expression of a transgene. This system provides a unique tool for regenerating transgenic plants carrying a repressed transgene and for efficiently de repressing its activity by a specific inducer at any time point of further development. PMID- 1303803 TI - Complementation of Saccharomyces cerevisiae auxotrophic mutants by Arabidopsis thaliana cDNAs. AB - An Arabidopsis thaliana cDNA bank has been constituted in a Saccharomyces cerevisiae expression vector based on the phosphoglycerate kinase (PGK) promoter and terminator. This bank was used to complement eight S. cerevisiae auxotrophic markers. All of them were corrected. These results confirm the quality of the bank and the feasibility of cloning plant genes by yeast mutant complementation. The cDNA complementing the ura1 yeast mutant was sequenced, analysed and shown to encode a dihydroorotic (DHO) dehydrogenase sequence. PMID- 1303804 TI - Overview of lupus erythematosus. PMID- 1303805 TI - Clinical relevance of immunologic findings in cutaneous lupus erythematosus. PMID- 1303806 TI - Clinical relevance of immunologic findings in scleroderma. PMID- 1303807 TI - Direct immunofluorescence patterns in clinically healthy skin of patients with collagen diseases. PMID- 1303808 TI - Clinical relevance of antibodies to Ro/SS-A and La/SS-B in subacute cutaneous lupus erythematosus and related conditions. PMID- 1303809 TI - Dermatologic criteria for classifying the major forms of cutaneous lupus erythematosus: methods for systematic discriminant analysis and questions on the interpretation of findings. PMID- 1303810 TI - Scleroderma/polymyositis overlap syndromes and their immunologic markers. PMID- 1303811 TI - Etiology and genetics of collagen diseases. PMID- 1303812 TI - [A physiological investigation of chronic electrical stimulation with scala tympani electrodes in kittens]. AB - A physiological investigation of cochlear electrical stimulation was undertaken in six two-month-old kittens. The scala tympani electrodes were implanted and electrically stimulated using biphasic balanced electrical pulses for periods of 1000-1500h in four ears. Four ears received implants for same period but without electrical stimulation. The other two ears served as normal control. The results indicated: 1) Chronic electrical stimulation of the cochlea within electrochemically safe limits did not influence the hearing of kittens and the normal delivery of impulses evoked by acoustic and electrical signals on the auditory brainstem pathway. 2) The wave shapes of EABRs were similar to those of ABRs. The amplitudes of EABRs showed a significant increase following chronic electrical stimulation, resulting in a leftward shift in the input/output function. The absolute latencies and interwave latencies of waves II-III, III-IV and II-IV were significantly shorter than those of ABRs. These results imply that there was no adverse effect of chronic electrical stimulation on the maturing auditory systems of kittens using these electrical parameters and the mechanism of electrical hearing should be further studied. PMID- 1303813 TI - [Effect of flavone glycosides of Epimedium koreanum on murine fibrinolytic system and apoplectic mortality]. AB - The enhancement of fibrinolytic ability of stimulated murine macrophages by flavone glycosides of Epimedium koreanum (TFG) was measured by the [125I]-fibrin coated plate method. The activity of the plasminogen activator (PA) induced by TFG was determined by a spectrophotometric assay. The activity of PA produced by TFG-stimulated macrophages was 0.731 IU/ML. (P < 0.01). TFG-stimulated macrophages showed rapid fibrinolysis. The activity of stimulated macrophages was approximately 2.8 fold that of the control. In in vivo experiments, the effect of TFG on spontaneously hypertensive and apoplexy rats (SHRsp) was very evident. The abiotic rate of TFG-stimulated rats was 5%, while that of the control group was 90%. TFG showed obvious hypotensive activity as well. PMID- 1303814 TI - [The kinetic observation of serum ketone body levels in surgical patients receiving MCT or LCT emulsions]. AB - The changes of serum beta-hydroxybutyrate concentrations in patients after receiving medium chain triglycerides (MCT) or long chain triglycerides (LCT) were studied. The patients were divided into two groups: in Group 1, the dose of fat was 0.14 g/kg.h for fat emulsion clearance test: and in Group 2, the dose was 0.06 g/kg.h for total parenteral nutrition (TPN) support. The beta hydroxybutyrate concentrations were estimated by an enzymatic method using Sigma's beta-hydroxybutyrate kit (Sigma Diagnostics, MO 63178, USA). The normal range of beta-hydroxybutyrate concentration in 30 healthy Chinese subjects was 1.04 +/- 1.42 mg/dl (range 0-3.88 mg/dl). In Group 1, we found that the concentrations of beta-hydroxybutyrate rose steadily after fat emulsion infusion. The concentrations in the medium chain triglyceride group were higher than those in long chain triglyceride group. The elevated concentrations of beta hydroxybutyrate gradually returned to normal levels when the emulsion infusion was stopped. In Group 2, the concentrations of beta-hydroxybutyrate in the patients were within the normal range. PMID- 1303815 TI - [Effect of lipopolysaccharide on protein kinase C activity in human erythrocytes]. AB - Membrane-associated protein kinase C activity was significantly increased after normal human erythrocytes were incubated with lipopolysaccharide. The effect was dose and time dependent. The results indicate that protein kinase C is activated by lipopolysaccharide in intact human erythrocytes. PMID- 1303817 TI - [Clinical and histopathological observation and determination of serum IgE levels in patients with dermographism]. AB - In 50 cases of dermographism, clinical and histopathological observations were made and serum IgE levels were measured. The results showed that serum IgE levels in patients with dermographism were increased significantly (P < 0.01) as compared with the control group. The role of increased IgE in the pathogenesis of the disease is discussed. PMID- 1303816 TI - [Investigation of maternal peripheral plasma concentration of PG in induction of labor by nutrition food inductive drug]. AB - The used nutrition food inductive drug to induce labor in 33 pregnant women, 22 of 33 succeeded and 11 failed. The PGs level in maternal peripheral blood was measured twice. One before taking and the second sample was drawn blood during second stage of labor. Another 13 pregnant women of spontaneous labor were measured as control group. The 6-keto-PGF1 alpha level was significantly increased in the succeeding group than in the tailed induced group, the PGE concentration seems no significant change in these three groups. The data suggested that the nutritional food inductive drug may accelerate the synthesis of prostaglandin in the succeeding group. PMID- 1303818 TI - [The value of serum tumor-associated glycoprotein 72 (TAG 72) in the diagnosis of malignancies]. AB - Serum TAG 72 concentrations of 110 normal subjects, 110 patients with benign diseases and 109 with malignant diseases were determined by a solid phase radioimmunoassay. Its levels in normal subjects were 1.6 +/- 1.5 u/ml (mean +/- SD, range 0-8.2 u/ml) and the cut-off limit was set at 4.6 u/ml. The positive rates in benign and malignant patients were 5.5% and 48.6%, respectively. Among the malignancies, 80.0% of ovarian and 63.6% of colon carcinomas had positive test results. The specificity for differentiating malignancies from benign diseases was 94.5% and the accuracy of diagnosis was 71.7%. The present study indicates that TAG 72 as a tumor marker is helpful in the diagnosis of malignancies. PMID- 1303819 TI - [DNA probe labeling with digoxigenin-dUTP and its application in gene diagnosis]. AB - In this paper, DNA probe labeling by the randomly primed incorporation of digoxigenin-dUTP is reported. The sensitivity of color reaction and hybridization were 32 fg and 200 fg, respectively, and both were specific for the target. Single-copy and multi-copy gene fragments among 2 micrograms human genomic DNA were detected by beta IVS II, Fr 3-42 and 3'HVR labeled with digoxigenin-dUTP. The results were consistent with a radioactive control assay. This method has been successfully used in the gene diagnosis of adult polycystic kidney disease. PMID- 1303820 TI - [Effect of the tumor promoter phorbol myristate acetate (PMA) on cell-mediated immunity. IV. PMA-induced modulation of mouse dendritic cell function]. AB - In the present study we investigated the in vitro effects of the tumor promoter phorbol myristate acetate (PMA) on the accessory function of mouse spleen dendritic cells (DC) in mitogenesis. The effects of the PMA, a protein kinase C (PKC) activator, depended on dose. If pretreated with < 50 ng/ml of PMA for 3 h, DC activity was enhanced by about two-fold; whereas > or = 200 ng/ml of PMA decreased DC activity with an inhibition rate about 50% (in early response DC activity showed a moderate increase). Our results indicate that the function of DC, a potent accessory population, can be further enhanced by a low dose of PMA. This is circumstantial evidence that DC activity can be up-regulatal via PKC activation. That a high dose of PMA inhibits DC activity might be a mechanism by which PMA promotes carcinogenesis. PMID- 1303821 TI - [Studies on human cervical carcinoma cell line. II. Establishment of HGPRT- cell line CC-80IAR2 and its biological characteristics]. AB - An HGPRT- cell line, CC-801AR2, was established from cloned human cervical carcinoma cell line CC-801 by using MNNG to induce cell mutation and 8-azaguanine (8-AG) to select the 8-AG resistant cells. The deficiency of HG-PRT in CC-801AR2 cells was proved by enzyme activity assay. This cell line was very sensitive to HAT medium. It was very similar in biological characteristics to CC-801, especially in that it retained its tumorigenicity when transplanted into nude mice. CC-801AR2 can therefore be used in somatic cell hybridization and gene transfer experiments. PMID- 1303822 TI - [Flow cytometric analysis of surface antigens on liquid nitrogen-stored cells]. AB - A high non-specific fluorescence background imposes serious interference on a flow cytometer in surface antigen assay for those cells stored in liquid nitrogen. The non-specific fluorescence comes from dead and dying cells, the permeability of whose membrane has been increased so that the fluorescence reagent can enter into the cells. To solve this problem, liquid nitrogen-stored PBMNC and Raji cells were screened on different gatings for surface antigen stained with fluorescence. It was observed that the high fluorescence background as well as debris can be gated out by means of gating on FALS, angle 90 degrees angle and PRFL. As a result, the percentage of surface antigen positive cells determined was close to that assayed in fresh samples. PMID- 1303823 TI - [The preparation and clinical use of a radioimmunoassay CA125 kit for the diagnosis of epithelial ovarian cancer]. AB - A self-made radioimmunoassay CA125 kit (using OC125 monoclonal antibody ascites offered by Dr. Bast Laboratory which was purified, solidified and labelled with 125I) was used for serum determination in 80 patients with epithelial ovarian cancer and in 40 standard antigen samples. The results demonstrated a statistically significant correlation between our self-made CA125 kit and an imported CENTOCOR CA125 kit (P < 0.001). Clinical experience before operation in 40 patients with epithelial ovarian cancer, 34 with endometriosis and 39 with other malignant ovarian tumors suggested that the self-made CA125 kit was more sensitive in diagnosing epithelial ovarian cancer than the other two diseases. Post-operative follow-up in 86 non-recurrent cases and 101 recurrent cases showed a 96% positive predictive rate and 91% negative predictive rate. It is concluded that self-made CA125 kit is very useful in monitoring epithelial ovarian cancer. PMID- 1303824 TI - [A case of acute lymphocytic leukemia transformed from malignant lymphoma]. AB - We report a case of malignant lymphoma in a 15-year-old male. He had erythema and nodular lesions, hepatomegaly, and splenomegaly with high fever for one month. Laboratory examination revealed a normal blood routine test, a few lymphomatic cells in the bone marrow, and histopathologic changes characteristic of malignant lymphoma in a skin biopsy. Two months later, a second bone marrow examination showed 90% prolymphoblasts. The peripheral blood count revealed WBC 108 x 10(9)/L; among these, prolymphoblasts accounted for 92%. The patient was diagnosed as acute lymphocytic leukemia, and died 2 days later. The diagnosis and transformation from malignant lymphoma to acute lymphocytic leukemia are discussed. PMID- 1303825 TI - [Application of 3 dimensional computer tomography to maxillofacial surgery]. AB - Three dimensional CT examination is a recently developed technique. Nine patients suffering from traumatic and developmental abnormalities were examined with this new method and the results were satisfying. Applying this technique, we routinely obtain a set of equal spaced, nonoverlapping, high resolution CT scans of the maxillofacial deformities. It provided a condition for facilitating surgical planning and improving quantitative of postoperation evaluation. PMID- 1303826 TI - [The nerve fiber projection of trigeminal ganglion cell to dental pulp, dentine and periodontal membrane in the rat]. AB - The nerve fiber projection of the trigeminal ganglion cell to dental pulp, dentine and periodontal membrane was investigated with the technique of anterograde radioautographic neuroanatomical tracing (ARNT) in the rat. Results showed that the innervation in dentine and pulp was not uniform. The nerve endings were most numerous in the pulp horn, and in the tubular dentine of the cusp and cervical regions. In the periodontal membrane, both large- and small diameter nerve fibers were found. And at least part of the innervation in the periodontal membrane was of trigeminal ganglion origin. PMID- 1303827 TI - [Chronic obstructive parotitis: a report of 92 cases]. AB - This article presents 92 cases (117 diseased parotid glands) of chronic obstructive parotitis with studies by clinical, sialographical, sequential quantitative scintigraphy methods and with investigation of the treatment. The nature of this disease is that various local factors cause obstruction of saliva flow resulting in recurrent swelling of parotid, in which the main feature in sialography is irregular dilatation of the main duct and branch duct. Sialographical manifestations can be divided into four types. Conservative, operative therapy and injection into diseased gland with 1% methyl violet are introduced to treat this disease. Long follow-up findings show that type I in sialography can be cured by conservative method, but other types to not respond to this method and should be treated by other methods, such as parotidectomy. We have used 1% methyl violet to treat cases who have swelling of parotid after conservative therapy. It is considered to be a simple, practical and good method and should only be used in this disease. There are no other side effects except swelling of parotid for a few weeks. Especially it can be used to treat the anterior part of main duct left over by parotidectomy, which still gives off purulent discharge. PMID- 1303828 TI - [Study on the recovery of 4 types of cultured cell after contacting varieties of dental casting alloys]. AB - Four types of cultured cell (Gin-1, Chang Liver, HEP-2 and L-929) were used in vitro to determine the cytotoxicity of 12 Chinese-Japanese Dental Casting Alloys from cell recovery ability. A new cytocompatibility detecting method--cell recovery test was established and recommended. This method can be able to observe the state of cell recovery through self growth cycle, diminish the side-effect of dead cell and its products on the living cells, nearly mimic the environment in vivo and study the inherited toxicology of cells. The application of computer photo-pattern analysis technique can acquire the objective and accurate data directly. PMID- 1303829 TI - [Clinical observation of the superoxide dismutase (SOD) and lipid peroxide (LPO) changes in oral-maxillofacial surgical patients]. AB - This article reports examination of superoxide dismutase (SOD) activity in RBC and lipid peroxide (LPO) content in the plasma of the oral-maxillofacial operation patients. The results showed that the LPO content in postoperation ascended remarkably compared with pre-operation (P < 0.001) and that the SOD activity rose also (P < 0.05). It was discovered that the difference of LPO content between the pre-operation and post-operation was closely relative with the difference of SOD activity, the operative time and the operation method (intra- or extra-oral approach). The results demonstrated that the operative damage resulted in the increasing of the reactivity of superoxide radical and LPO and that the rising of SOD activity was probably the compensation of the body. PMID- 1303830 TI - [Binding of Actinomyces viscosus to collagen]. AB - The ability of collagen adsorbed on apatitic surfaces to promote adhesion of A. viscosus was studied. Treatment of hydroxyapatite (HA) with human type I or type III collagen strongly promoted adhesion of A. viscosus LY7. TEM observations revealed that A. viscosus also attached to fibrils prepared from human type I collagen. The alpha(2) polypeptide derived from type I collagen exhibited moderate activity in promoting binding. Mutans of A. viscosus which possess type I fimbriae, but not type 2 fimbriae or no fimbriae, also bound to collagen treated HA. This suggests that the adhesin responsible was associated with type I fimbriae, strains of A. israelii and A. odontolyticus also exhibited strong binding to collagen-treated HA. The avidity of Actinomyces species for collagen would seem to be partially responsible for the high proportions of these organisms found on root surfaces. PMID- 1303831 TI - [An experimental study of dan sheng improving the mandibular bone fracture healing]. AB - Sixty-four rabbits were used in this study, experimental bone defects were made in notch of the mandibular bone angle. Dan sheng was used in experimental groups. A pieces of bone at the edge of the defect was taken and observed by electron microscope in different period. The results were as follows: 1. The amount of osteoblast increase clearly. 2. The synthesis of protein was vigorous in fibroblast appeared as nuclear depression, nucleoli locating at one side and formation of endoplasmic reticulum bubble. as Therefore, we think that dan shen would take a role of improving the mandibular bone fracture healing. PMID- 1303832 TI - [A preliminary study on cross anastomoses between facial and accessory nerves and reconstruction of motor unit]. AB - In a new operating model, the buccal branch of facial nerve of rabbits, which originally controls the muscles composed of small motor units (MU), was transposed and cross-anastomosed with the accessory nerve which controls the sternocleidocephalic muscle composed of larger MU. One year later, fine filaments of facial nerve were dissected and stimulated, electrophysiological and biomechanic examinations of single MU in sternocleidocephalic muscle were carried out; the total number and percentage of 3 types of muscle fiber were counted according to polyhistochemical and histological methods as we reported formerly; the motor fibers were counted according to nerve AChE direct-coloring method and the innervation ratio was calculated. The results showed that the facial innervation ratio increased by 2.2 to 4.4-fold. That the largest value of TwT recorded in one of single MUs reached to 112.9 mN, suggested that the number of muscle fibers innervated by this facial nerve axon was much more than it did. That there was no type grouping phenomenon appeared in polyhistochemical examination implied that the facial nerve fibers regenerated along the old route offered by original MU, which tended to reneurotize all of muscle fibers of the original MU. PMID- 1303833 TI - [An epidemiologic study of oral maxillofacial disorders in 384 mental retardation in children]. PMID- 1303834 TI - [Flow cytometric analysis of squamous cell carcinoma of the oral and maxillofacial region]. AB - Fifty fresh tissue samples and fifty paraffin embedded specimens from squamous cell carcinoma of the oral and maxillofacial region were analyzed for nuclear DNA content and cell kinetics by flow cytometry (FCM). Mean DNA index (DI) was 1.154, and 59% of them showed aneuploidy patterns. Mean S phase cell population, which represents the "proliferative activity", was 22.62%. With the increase of surgical stage, aneuploid population rose from 51.7% to 82.8%, and with the increase of histology grade, it rose from 54.17% to 71.4%. S phase cell population also showed a tendency to increase with the increase of surgical stage or histology grade, and in those with cervical metastasis. The results indicate that nuclear DNA analysis by FCM is quite useful as a supplement to histology diagnosis and evaluation of malignant grade of squamous cell carcinomas of the oral and maxillofacial region. PMID- 1303835 TI - [The numbers and distribution studies of natural killer cell, T cell subsets in peripheral blood and local infiltration in patients with squamous cell carcinoma of the oral cavity]. PMID- 1303836 TI - [Prevalence of root surface caries in 791 middle-elderly population assessed with Katz index method]. PMID- 1303837 TI - [Measurements of masticatory in anodontia wearing full denture with porcelain or resin teeth]. PMID- 1303838 TI - [Intraoral approach in correcting the hypertrophic mandibular angle and masseter muscle]. PMID- 1303839 TI - [The study on the application of 2 rigid composite resins veneers]. PMID- 1303840 TI - [Application of auxiliary and sectional arch technique to fixed appliances]. PMID- 1303841 TI - [Masticatory efficiency]. PMID- 1303842 TI - [Skin tests in patients with history of anaphylactic reaction to penicillin]. AB - Skin tests including immediate patch test (IPT), skin prick test (SPT), or intradermal test (IT) with penicillin G(PenG) and SPT with benzylpenicilloyl human serum albumin (BPO) were done in 54 patients with history of anaphylactic reaction to penicillin or shock of unknown cause. 26 patients with penicillin allergy were diagnosed. BPO specific IgE measured with ELISA gave a lower positive rate in detecting penicillin allergy as compared with the tests mentioned above. The results of skin tests in 26 patients showed that IPT with 500 IU/ml of PenG was not only accurate but also safe. Because no skin injury occurred and PenG residue could be washed out, the amount of PenG penetrated into skin is very small, thus, adverse reactions were very few. It is recommended that IPT with PenG in 500 IU/ml concentration is performed at the beginning of skin tests. If negative, SPT and then IT both with a solution of 500 IU/ml concentration are carried out, until a positive reaction occurs. This procedure is relatively accurate, simple and safe. PMID- 1303843 TI - [Relationship between levamisole and encephalitis syndrome]. AB - The results of a cohort study of 92,346 labour population for probing the relationship between levamisole (LMS) and encephalitis syndrome was reported. There were five patients suffering from the disease in an exposed group (E) of 10,911 people within two months after taking LMS as an anthelmintic for mass treatment, the incidence of the disease is 4.58/10,000. The nonexposed population was divided into two control groups the first group (N1) includes 37,990 people living in the mass treatment villages and the other group (N2) consists of 43,445 people living in the adjoining villages without mass treatment. None in the two control groups suffered from the syndrome or any other encephalitis-like disease within the same period. Statistical tests for the differences between E and either N1 or N2 separately is highly significant. (between E and N1: P = 0.000553, P < 0.001; between E and N2: P = 0.000325, P < 0.001). The overall attributable risk (AR) is 45.8/100,000 and that for female is 93.8/100,000. However, the difference between the incidence rates of the disease in female and male is not statistically significant (P > 0.025). It is shown that LMS is obviously the causative factor of the disease. PMID- 1303844 TI - [Clinical study of 76 cases of counterattack induced by acute organic phosphorus pesticides intoxication]. AB - 76 cases of counterattack induced by acute organic phosphorus pesticides intoxication were analysed. The activity of cholinesterase did not show a significant difference before the counterattack as compared to that after the counterattack (P > 0.05). The average dosage of atropine for pre-atropinization was 58.6 +/- 2.7 mg/h and it was 203.9 +/- 17.7 mg/h between the post counterattack and the second atropinization (P < 0.01). Compared the mortality in reaching and non-reaching the second atropinization was 22.8% VS 100% (P < 0.01). The survival rate was 37.5% in collaborating blood transfusion cases and 20.6% in noncollaborating ones (P > 0.05). We also studied on the treatment, mechanism, precursory symptoms, causes of death, degrees of intoxication and pesticide types etc. PMID- 1303845 TI - [Randomized clinical controlled cross-over trial (RCT) in the prevention of blood transfusion febrile reactions with small dose hydrocortisone versus anti histamines]. AB - RCT was used in 73 patients who had experienced blood transfusion febrile reactions. For further two transfusions Benadryl was used before the first transfusion and hydrocortisone before the second in 36 patients. In the other group of 37 patients hydrocortisone was administered before the first the and Benadryl before the second transfusion. The effective rate of preventing transfusion febrile reactions with Benadryl (72.6%) was not significantly different from that with hydrocortisone (86.3%). PMID- 1303846 TI - [Gene diagnosis and successful reversion in a patient with preleukemia]. AB - According to the FAB classification, a patient (case 1) could not be diagnosed as MDS-RA, although she had clinical features of MDS, as compared with another patient (case 2) who was diagnosed as RAS and had abnormal karyotype (20q- and 5q ) of bone marrow (BM) cells. BM cells of the two patients were SCD (sister chromatid differentiation) negative. Rearrangement of c-erbB and c-erbA was found in the genome of the BM cells in both patients, when southern blot hybridization was performed with probe v-erbB+A. Therefore, case 1 could be diagnosed as preleukemia. During a period about 3 years of treatment with the drug stanozolol in case 1 there was good effect and successful reversion was obtained. She had then normal hematologic and cytogenetic patterns of BM and PB and the rearrangement of c-erbB of BM cells also disappeared. She has worked for two years since then. The mechanism of effective treatment and successful reversion was discussed briefly. Probe v-erbB was shown to be useful in investigation of gene diagnosis of preleukemia or MDS (shown elsewhere). PMID- 1303847 TI - [Relation between left ventricular mass indexes and cardiac function in hypertensive patients: an approach with Doppler echocardiography]. AB - 73 age-matched hypertensive patients, 46 men and 27 women, were divided into the four groups according to left ventricular mass indexes (LVMI) and normal control groups were established correspondingly. Doppler and M-mode echocardiography were used to assess the systolic and diastolic functions of left ventricle (LV) and the alterations of heart construction. It was shown that when the LVMI increased slightly, the internal dimension and systolic function of LV had no significant change, but the diastolic function became abnormal and the left atrium enlarged. When the LVMI increased significantly, both the left atrium and left ventricle enlarged and the systolic and diastolic functions of LV were impaired. It is concluded that increase of LV mass may be present in the early stage of hypertension and left atrial enlargement is an early sign of left ventricular diastolic dysfunction, which occurs before systolic dysfunction in the patients with essential hypertension. PMID- 1303848 TI - [Immunohistochemical study of hepatitis E virus antigen in liver tissues from patients with type E hepatitis]. AB - Hepatitis E virus antigen (HEV Ag) has been identified in liver tissues of 6 out of 14 patients with type E hepatitis by direct immunoperoxidase staining, using anti-HEV-IgG-HRP. HEV Ag was found to be diffusive or inclusive in the cytoplasm of hepatocytes were scattered and isolated, but might aggregate in some parts where the liver damage was severe. We found that lymphocyte invaded the HEV Ag positive hepatocyte. These phenomena suggest that the liver damage is related to immunoreaction. HEV Ag was not found in the liver tissues of stillborn fetus and newborn baby from woman patients with hepatitis E. To detect HEV Ag in liver with direct immunoperoxidase method, using anti-HEV-IgG-HRP is more efficient than using anti-HEV-IgM-HRP. PMID- 1303849 TI - [Immunodiagnosis of tuberculous meningitis]. AB - The detection of special anti-mycobacterial antibodies in cerebrospinal fluid (CSF) were evaluated. Among all the common coated antigens, it was found that PPD was the most potential one. Seven detecting methods were compared. It is shown that the classic ELISA technique is worth recommending. The results of the experiments, revealed that absorbance method was better than titration method, IgG antibody was more sensitive than IgM antibody and the sensitivity rate of IgM was not related with the course of the disease. The factors which influenced the levels of IgG antibody to mycobacterial antigens include focal signs and abnormal CT findings. False positive results were found in detecting anti-mycobacterial antibodies in a few cases. Immunodiagnosis was an useful method in diagnosing tuberculous meningitis and this study has provided ample theoretical basis for popularizing this technique. PMID- 1303850 TI - [Is the renal dopamine involved in the sodium retention in the nephrotic syndrome?]. AB - Urinary dopamine (DA) and sodium excretion in patients with nephrotic syndrome (NS) were studied under various sodium loading in metabolic ward. Twenty patients and 10 age-matched normal volunteers were enrolled in this study. When they were on a low-salt diet (34 mmol/d), urinary excretion of DA and sodium in patients with heavy edema were much lower than that in normal controls, while in patients with mild or without edema, urine DA and sodium excretion did not decrease significantly, but were not mobilized on sodium loading (170 mmol/d), and the plasma renin activity and aldosterone were not completely suppressed as well. The decrement of urine DA excretion was independent of Ccr or the severity of renal tubule lesions, but was associated with the severity of proteinuria. When the proteinuria reduced, urine DA and sodium excretion increased. From the above observations, we might assume that the abnormal retention of sodium and water in NS was due partly to a failure to mobilize DA in the kidney and the change of the physical environment in renal tubule caused by heavy proteinuria was responsible for it. PMID- 1303851 TI - [Resistant rate to antibiotics in Tian Tan Hospital for 3 years]. AB - The resistance to antibiotics of the 985 clinical isolates collected in Tian Tan hospital was studied. The results showed that S. aureus had a resistant rate of more than 90% to penicillin and was also highly resistant to erythromycin. Methicillin resistant Staphylococcus Aureus (MRSA) was isolated in 15.6% of all the isolates with S. aureus. The isolation rate of MRSA is lower than that in other countries or districts of West Pacific Area. K. pneumonia and other Gram negative bacilli had a resistant rate of 0.6% to amikacin and P. aeruginosa was all sensitive to Polymyxin-B. PMID- 1303852 TI - [The advances in blood coagulation, anticoagulation and fibrinolytic system in China]. PMID- 1303853 TI - Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma. AB - We studied the destructive effect of hyperthermia at sub-photocoagulation level of 45-60 degrees C on melanomas. Optimal conditions for spreading of heat into tissue are a wavelength of 700-900 nm, a temperature of 45-60 degrees C, an exposure time of 1 minute or more, and a beam diameter of several millimeters. In hamsters with subcutaneous melanomas we obtained a tumour necrosis of 6 mm depth at 60 degrees C and one minute exposure time. We performed transpupillary thermotherapy (TTT) with a diode laser at 810 nm in patients with choroidal melanomas prior to enucleation. Treatment is based on the fortunate situation that irradiation at this wavelength combines optimal tissue penetration with a low absorption by clear ocular media of 5% or less. In 3 TTT-treated eyes histopathology showed a depth of necrosis of 0.9, 3.4, and 3.9 mm. TTT may become a new useful treatment modality for choroidal melanoma but its ultimate value has yet to be assessed. PMID- 1303854 TI - Lamellar excimer laser keratoplasty: reproducible photoablation of corneal tissue. A laboratory study. AB - We examined the depth of ablation of the recipient bed with different counts of oscillations of excimer laser beam, to determine the correlation between planned and real depth. The ablation rate per oscillation was tested preoperatively by blackened photographic paper of defined thickness and thus was calculated to be 5 microns. Forty pig eyes were used for the first study. Each eight eyes were ablated in the planned depth 100 microns, 200 microns, 300 microns, 400 microns and 500 microns. The corneal thickness was measured with an ultrasonic pachymeter before and after the procedure. The depth measured after the photoablation was 99.4 +/- 36.4 microns for 100 microns planned depth, 186.7 +/- 55.3 microns for 200 microns, 298.4 +/- 68.5 microns for 300 microns, 373.9 +/- 65.7 microns for 400 microns and 480.1 +/- 59.3 microns for 500 microns. Comparing the depth measured after the photoablation to planned depth, there was a significant correlation (correlation coefficient: R = 0.93; p < 0.0001). Five other corneas trephinated from pig cadaver eyes were ablated from the endothelial side to the desired thickness (100 to 500 microns) of lamellar graft. In a second step a donor mask was placed onto the cornea and a laser light spot was led until perforating on all sides. The lamellar keratoplasty was completed by suturing the corneal graft into the bed. Macroscopic and microscopic examination of sutured eyes after fixation showed a good fit of wound margins and stromal interface. These results indicate that excimer laser is useful for reproducible corneal photoablation in lamellar keratoplasty. PMID- 1303856 TI - Visual acuity following treatment of bilateral congenital cataracts. AB - Several studies have indicated that operation during the first months of life in children with dense congenital cataract improves the final visual acuity. In the current study seven otherwise healthy children operated on before the age of fifty-six days are compared with seven children operated on after the age of three months. The patients were followed by a team consisting of a paediatric ophthalmologist, a contact lens optician and an orthoptist. They were treated with contact lenses, spectacles with near addition and occlusion therapy when needed. Visual acuity was initially tested with preferential looking technique and later with Snellen optotypes. In the early treated group the visual development was almost normal with a final visual acuity of 20/20, while in the late treated group no patient obtained better visual acuity than 20/100. The findings indicate that dense congenital cataract should be treated before the age of three months. PMID- 1303855 TI - Alfentanil/promazine versus meperidine/promazine as a sedative regimens during local analgesia for cataract operation. AB - The influence of two intravenous (IV) sedative regimens on intra-ocular pressure (IOP) was investigated in conjunction with retrobulbar local analgesia. Forty patients of either sex, and similar age with body weight within 40-90 kg were allocated equally and randomly to two groups: Group A (alfentanil/promazine) and group M (meperidine/promazine). Measurement of IOP, systolic pressure, pulse rate, respiratory rate, PaCO2, PaO2 and O2 saturation were made before operation, after premedication, after IV sedation and post-operatively. In the Alfentanil group there was significantly stronger decrease of IOP (p < 0.001). In group A the IOP dropped from 18.1 +/- 3.2 mm Hg to 10.3 +/- 2.7 mm Hg, i.e. 43%, while in group M the reduction IOP was from 17.6 +/- 3.5 mm Hg to 12.6 +/- 1.9 mm Hg, i.e. 28.4%. Meperidine caused a significant increase in PaCO2 (4.2 +/- 0.3 mm Hg), however this increase was not sufficient to cause the IOP alterations. The oxygen saturation was lower in group M (decreased by 1.5 +/- 1% in group M versus decrease by 1.0 +/- 1.2% in group A). Cardiovascular parameters were more stable in group A. In conclusion the alfentanil regimen produced a better reduction of the IOP with excellent sedation, operative condition and least anaesthetic side effects. PMID- 1303857 TI - High incidence of asymptomatic urogenital infection in patients with uveitis anterior. AB - Acute anterior uveitis (AAU) may be associated with systemic infectious or inflammatory disease. We examined 92 patients with the first attack of acute anterior uveitis; all patients were free of any extraocular symptoms. A thorough clinical examination did not reveal any systemic underlying disease. In the course of microbiological examination, however, a high incidence of asymptomatic infection of the urethra and/or cervix with ureaplasma urealyticum, chlamydia trachomatis and mycoplasma hominis was found. Infections with ureaplasma were significantly more frequent in patients with AAU when compared with a sex- and age-matched control group. There was no statistically valid association of these infections with the HLA-B27 phenotype in the patients. The higher rate of urogenital infections in patients with AAU may reflect a higher rate of sexual promiscuity. Transmission of infectious agents seems to be one possible factor in the pathogenesis of AAU. PMID- 1303858 TI - Long-term results of systemic chemotherapy for ocular cicatricial pemphigoid. AB - Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, blinding, autoimmune disease that scars mucous membranes. We studied the long-term outcome in 104 consecutive patients (average follow-up: 4 years) to determine whether complete remission could be achieved following a course of treatment with immunosuppressive drugs. We found that prolonged periods of remission off therapy are maintained in about one third of OCP patients. Follow-up must be continued for life as relapse occurs in approximately one third of cases. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation and the incidence of extraocular involvement did not bear a prognostic significance. The mechanism which underlies the differing responses to therapy is not yet known. PMID- 1303859 TI - Gonioscopic changes in eyes with posterior chamber intraocular lenses. AB - The aim of this study is to determine the effects of posterior chamber implantation on angle structures. First, without previous knowledge of the position of lens haptics, 360 degrees gonioscopy was performed and any changes in the angle structures were recorded. Then, the pupil was dilated to determine the exact position of the intraocular lens haptics. The apposition of peripheral iris to angle structures or, at least, the narrowing of the angle corresponding to the lens haptic position was observed in almost all of the 117 examined eyes, with no difference found between bag and sulcus implantation. Peripheral anterior synechia overlying the lens haptic was observed in 49 (41.8%) of 117 eyes. Interestingly, we also noted that there was marked and well-limited clumping of pigment in the angle at 6 o'clock position in 67 (57.2%) of 117 eyes. In conclusion, we feel that posterior chamber intraocular lenses are not completely innocuous to the angle structures. PMID- 1303861 TI - Myopia progression in young school children and intraocular pressure. AB - Studies of the literature have given the impression that intraocular pressure (IOP) may influence the refractive error (RE); the reason being that the IOP in some studies is higher among myopic subjects than among emmetropes and hypermetropes. The progression of myopia was studied in 49 children, aged 9-12 years, over a period of 2 years. The rate of progression was 1.14 D/2 years and the IOP 16.6 mmHg. Comparison of the rate of progression between children with an IOP above 16 mmHg and those with an IOP of 16 mmHg or less showed a statistically significant difference: 1.32 D/2 years as compared to 0.86 D/2 years. These results are supported by ultrasound measurement of the axial length. The author recommends that measurement of IOP should be included in the design of studies of myopia progression. The reason for this is, that it would appear that those persons most at risk of developing higher degrees of myopia have a high IOP. PMID- 1303860 TI - Binocular contrast summation and inhibition in amblyopia. The influence of the interocular difference on binocular contrast sensitivity. AB - The monocular contrast sensitivity loss in amblyopia is well documented. We investigated the influence of interocular sensitivity difference on binocular contrast sensitivity in amblyopia. Monocular and binocular contrast sensitivity functions of six amblyopes (three strabismic and three anisometropic) were measured. The monocular contrast sensitivity loss depended on the type of amblyope. Anisometropic amblyopes generally showed high frequency losses. Strabismic amblyopes showed losses at both low and high spatial frequencies. Binocular performance was assessed in terms of binocular ratios (binocular/non amblyopic). A binocular ratio greater than 1 indicates binocular summation (binocular > monocular) while a ratio less than 1 shows binocular inhibition (binocular < monocular). In all subjects, the binocular ratio depended on the difference between the amblyopic and the non-amblyopic eye. Minimal interocular difference produced binocular summation, the magnitude of which decreased as the difference between the two eyes increased. Further increases in the monocular difference produced binocular inhibition. Anisometropic amblyopes showed a greater degree of binocular summation at low spatial frequencies compared to strabismic amblyopes. Both types of amblyopes showed binocular inhibition at high spatial frequencies. Clinical implications of binocular summation and inhibition in amblyopia are discussed. PMID- 1303862 TI - Retinal oscillatory potential abnormalities in patients with chronic renal failure, before and after dialytic treatment. AB - Nineteen patients with chronic renal failure were studied, oscillatory potentials (OPs) being recorded shortly before and after dialytic treatment. Mean values of either onset latency (O1 latency) and duration of the complex (O1-N4 inter-peak latency) were found to be significantly longer in patients than in controls (p < 0.001). Most of the patients (12) showed a pathological prolongation of latency (> 2.5 SD). Amplitude changes also affected OPs, but earlier components were reduced to a lesser degree than the later ones, as shown by statistical analysis. Moreover, seven patients showed an almost complete loss of O3 and O4 peaks. Latency changes may be transiently reversed by dialysis, suggesting a functional impairment of the retinal response; the loss of later components is a more persistent abnormality probably related with a structural damage. PMID- 1303863 TI - Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis. AB - It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily. PMID- 1303865 TI - Comparative studies of the carbohydrate of human gamma-crystallins from fetal and adult lenses with agglutinins. AB - Using gel chromatography of Sephadex G-75 superfine connected with Sephadex G-50 fine column, three human gamma-crystallins (gamma 1, gamma 2, gamma 3) could be obtained. Seven agglutinins (LCA, SBA, DBA, PNA, BSL, RCA and UEA) were used to detect the sugar of sub-gamma-crystallins, which had been transferred to nitrocellulose membrane and finally stained with ABC reagents and the substrate of HPR. These results suggested that gamma 2- and gamma 3-crystallins contain sugar, but gamma 1-crystallin has no sugar. There is a decrease of carbohydrate of gamma 2 and gamma 3 as the development of the lens (esp. the former). It was postulated that in gamma-crystallins (gamma 2, gamma 3) the sugar components helped stabilizing the molecular structure (folding polypeptide, prevent protein breaking). The sugar components decreased with age by the post-translation modification. PMID- 1303866 TI - Posterior chamber IOL implantation in traumatic cataract with injured complications. AB - Twenty-five cases of posterior chamber IOL implantation in traumatic cataract with complications associated with primary injury were reported. The operating methods were described and the post-operative complications were discussed. Seventy-two percent of patients have the correct vision over 20/40. It is suggested that the posterior chamber IOL can be implanted in traumatic cataract with some injured complications. PMID- 1303864 TI - Potassium iodide and acrylamide fluorescence quenching studies on gamma crystallins of human lenses in development and aging. AB - gamma 1-, gamma 2- and gamma 3-crystallin (corresponding to gamma s-, gamma C- and gamma D-crystallin respectively) of human fetal, 2 year and 20+ year old lenses are separated by Sephadex gel chromatography. Iodide and acrylamide are used to quench the tryptophane fluorescence of sub-gamma-crystalline fractions and Ksv and fa values are calculated. The results show that iodide has no clear quenching effects on all gamma-crystallins, the quenching effects of acrylamide on the tryptophan fluorescences of gamma 1-, gamma 2- and gamma 3-crystallin from lenses of the same age have little differences, and the quenching rates of tryptophane fluorescences of gamma 1-crystallin decreases and that of gamma 2- and gamma 3-crystallin increase with age. These results indicate that all tryptophan residues in these three gamma-crystallins lie in hydrophobic environments of molecule and their exposure degree is in the order gamma 2 < gamma 3 < gamma 1. The tryptophan exposure of gamma 2 and gamma 3 increase (gamma 2 > gamma 3) and of gamma 1 decrease with age. The age related change of gamma 1 may be related to the changing of structure or containing of new constituents. Although the tryptophan exposure in gamma 3 is higher than that in gamma 2, the change of structure with age in gamma 2 is more prominent than in gamma 3. PMID- 1303867 TI - Modern surgical treatment of congenital subluxated lenses. AB - Traditional surgical management of subluxated lenses is usually associated with a high incidence of operative and postoperative complication and a poor visual outcome. We treated a series of 14 patients (26 eyes) whose visual acuity could not be improved with optical correction (phakic or aphakic) with modern microsurgery and automated suction-cutting devices. Preoperative visual acuity ranged from 0.05 to 0.3. Improvement in post-operative visual acuity was documented in all operated eyes, ranging from 0.4 to 1.0 during a follow-up period ranging from 6 to 59 months (medium 43 months). The only complication was a small accidental cut in the pupillary border in three eyes. Other complication did not occur. PMID- 1303869 TI - Quantitative evaluation of flicker ERG waveforms in low vision patients. AB - Flicker electroretinograms (FERGs) of 30Hz were recorded for 46 eyes (23 cases) of low vision, including 38 eyes with retinal diseases and 8 eyes with optic neuropathy, and for 39 normal eyes (33 cases). The recorded wave forms were analysed by two methods: (1) to measure the peak to peak amplitude and pseudophase directly, and (2) to measure the amplitude and phase of fundamental response component (30Hz) by discrete Fourier transform (DFT). The abnormality ratios between these two methods were compared in low vision patients. All the eyes with optic neuropathy showed normal flicker ERG, the abnormality ratios of directly measured amplitude and the amplitude by DFT were 60.9% in 28 eyes and 71.7% in 33 eyes with retinal diseases respectively, the difference being no statistically significant (P > 0.05), while the abnormality ratios of directly measured pseudo-phase and the phase by DFT were 60.9% in 28 eyes and 82.6% in 38 eyes with retinal diseases respectively, the difference being statistically significant (P < 0.05). These results suggest that FERGs are an objective way to test the retinal function, and DFT for flicker ERGs are more useful in quantitative evaluation of the retinal function. PMID- 1303868 TI - Retinoma and phthisis bulbi of retinoblastoma. 1. Clinical and genetic analysis. AB - Retinoma and phthisis bulbi of retinoblastoma are rare entities found in retinoblastoma patients and their relatives. Eleven cases of phthisis bulbi of retinoblastoma and 9 cases of retinoma were identified from 1966 to 1991 in our center. The clinic data show that retinoma and phthisis bulbi are closely related to the retinoblastoma gene. Enucleation should be carried out as soon as possible without hesitation for the phthisis of eyes with retinoblastoma. Genetic counseling and frequent observation should be paid attention to retinoma patients and their offspring. The mechanism of retinoma developed is discussed. We propose that the diversity of second mutation might be the cause of retinoma. PMID- 1303870 TI - The spectral VEP in normal subjects and dichromats. AB - The spectral VEP in 13 normal subjects (25 eyes), four cases (8 eyes) of protanopes and 8 cases (15 eyes) of deuteranopes were tested. In normal subjects, the shortest latencies of N1, P1, N2 were in 560 nm and the greatest amplitudes of N1-P1 and P1-N2 were 560-570 nm, around which the latencies were delayed and the amplitudes were decreased as the wavelengths of stimulative light increased or decreased gradually. The spectral VEP pattern of deuteranopes was similar to the normal subjects. In the protanopes, the shorter latencies of N1,P1,N2 and greater amplitudes of N1-P1, P1-N2 appeared in 520-530 nm and 570 nm, forming the two-thoughs and two-peaks shapes, with the shortest latencies and the greatest amplitudes in 520-530 nm. There were statistically significant differences of amplitudes and/or latencies in some wavelengths between the protanopes and normals and between the deuteranopes and normals. PMID- 1303871 TI - Visual functions and trace element metabolism in tobacco-toxic optic neuropathy. AB - Visual functions and nutrition metabolic characteristics were studied in 8 subjects (16 eyes) with tobacco-toxic optic neuropathy (TTON). Their visual functions tested by psychophysical and electrophysiologic methods showed that 1: 1. central vision diminished in 16 eyes, 2. dyschromatopsias were found in 14 tested eyes, 3. bilateral symmetrical central or cecocentral scotomas were the visual field characteristics in all cases, 4. PVEP were severe abnormal in 3 spatial frequencies in all cases and 56.3% of 15' checkboard PVEP showed flat responses, which indicated the impairment of optic nerve dominated by the central field. However, the preserved visual responses could be obtained by FVEP test in 14 tested eyes even though their visual acuity were between the range of 0.02-0.2 and flat PVEP responses. The II and III wave latencies of primary stage were more prolonged than those of control group (P < 0.01), which further indicated the preferential demyelination corresponding to the papillomacular bundles, 5. ERG showed slightly attenuated amplitudes in 5 of 8 tested eyes, which indicated the secondary and mild retinal lesion. On the other hand, TTON occurred on a background of long-term, heavy smoking, drinking, emaciation and malnutrition bodies with low serum zinc level. PMID- 1303873 TI - Lasers in ophthalmology. PMID- 1303872 TI - Effects of qingkailing on experimental allergic uveitis in rabbits. AB - Experimental allergic uveitis (EAU) in rabbits was induced by single intraocular injection of bovine serum albumin (BSA). The average of protein concentration in aqueous humor of untreated group of rabbits was 14.33 +/- 1.21 mg/ml and the count of tritiated thymidine (3H-TdR) incorporated into lymphocyte T was 3,987 +/ 1,156cpm/10(6). The specific antibody responses to BSA in the serum and the aqueous were 0.508 +/- 0.034 and 0.369 +/- 0.019 (OD) respectively. Meanwhile, the effect of Qingkailing on EAU was observed in comparison with dexamethasone as the positive control. The inflammatory reactions of rabbits treated with Qingkailing were remarkably diminished clinically and pathologically. The amount of protein concentration in aqueous of the treated rabbits was 5.79 +/- 2.19 mg/ml (P < 0.01) and the count of 3H-TdR incorporation was 2,455 +/- 981cpm/10(6) (P < 0.05). The responses of antibody in the serum and the aqueous were 0.414 +/- 0.059 and 0.253 +/- 0.041 (P < 0.01) respectively. Our observations indicate that Qingkailing has a positive therapeutic effect on EAU in the rabbits and sustain the suggestion that this drug is capable of suppressing immune and phlogistic reactions. PMID- 1303874 TI - Radial keratotomy: eleven-year experiences. AB - During the period from 1980 to 1991, Radial Keratotomy (RK) had been done by the author under topical anesthesia in more than 10,000 cases, mostly on both eyes at the same time. Those patients had myopia with a preoperative refractive error between 1.5 and 20.0 diopters (D). The surgical technique consisted of 4, 8, 16 incisions using a diamond knife with micrometer and the diameter of the central clear zone was mostly 3.0 mm and determined by preoperative refractive error. Many different procedures were tried to improve the effect of RK, including redeepening intentional microperforations at 1.5 mm, 3 mm, 5 mm distance from the corneal center. But these procedures had no significant effect 6 months after the operation. Complications such as infection, glaucoma, cataract, etc. were almost none. Results of RK on long term follow up showed hyperoptic tendency, and the visual fluctuation were none or minimal. PMID- 1303876 TI - [Effect of betadine as a mucosa-disinfectant]. AB - According to the previous data in the literature, the Betadine is an effective disinfectant in daily practice so its spreading is much desirable. The Betadine considerably decreases the oral flora. Its use may be advisable in case of dental and oral surgical interventions, before local anaesthesia, and in the perioperative period to support the oral hygiene. PMID- 1303875 TI - [Biomechanical testing of DIAKOR implants by photoelastic stress analysis]. AB - Diakor aluminium oxide implants of different forms and sizes have been investigated and compared by photoelastic stress analysis. On forming the conditions of investigations the authors aimed at the modelization based upon the physiological direct implant-bone contact, installing implants having resin that is optically double refractive. In the sample results show a move advantageous stress relation at multi grooved implants of extended dimensions. PMID- 1303877 TI - [Genetic subjects in Hungarian dental literature]. AB - The author classifies the Hungarian dental publications on genetical aspects into the following groups: 1. tooth and dental arch characteristics, disorders and illnesses, 2. oral cavity and surrounding area characteristics, disorders and illnesses, 3. mandible and surrounding bone characteristics, disorders and illnesses, 4. hereditary illnesses involving oral symptoms, 5. summarizing publications. PMID- 1303878 TI - [The effect of fluoridated milk on caries reduction over 12 years]. AB - The aim of the study was to assess the caries-preventive effect of fluoridated milk after 12-years of consumption, including 2 years interruption. DMF mean values of 162 institutionalized children aged 7-to 14 years were compared with DMF mean values of 139 institutionalized control children of the same age. The children consumed 200 ml milk daily, implemented with 0.4 mg -0.75 mg F(-)- depending on their age--between 1979-1984, after 2 years interruption they got fluoridated milk or cocoa-milk twice a week during 10 years. In the test group the ratio of caries-free children averaged more than 10%. The caries prevalence in the permanent dentition showed statistically significant reduction. The caries reduction regarding all groups was 36.78% in case of DMF-T, and 40.02% of DMF-S. According to our results the consumption of fluoridated milk in institutionalized children proved to be effective also in the long run. PMID- 1303879 TI - [Importance of the styloid process syndrome in the differential diagnosis of facial pain]. AB - The reported 2 cases of processus styloideus syndrome deserve attention because of their rarity. In the case of complains of uncertain origin and radiating chiefly into the tongue also the processus styloideus syndrome is to be taken into consideration. With the surgical treatment, after having the diagnosis, a well treated illness can be separated from the group of those illnesses in which the main problem is facial pain. PMID- 1303880 TI - [Familial occurrence of Gorlin-Goltz syndrome]. AB - A case of familial Gorlin-Goltz syndrome is described from the clinical point of view. The importance of early diagnosis, adequate treatment and care are emphasized. PMID- 1303881 TI - [Comment on the article "Pharmacokinetic studies of various fluoride compounds in rats", by Drs. Solymosi, Kertsz, Ritlop and Banoczy"]. PMID- 1303882 TI - [Jzsef Iszlai. Commemoration of the 150th anniversary of his birth]. PMID- 1303883 TI - [The use of a radial osteocutaneous flap in mandibular reconstruction]. AB - The authors make known the indications and method of the free osteocutaneous forearm flap. They have established from the literature data, and by their own experience of 4 cases, that the use of free osteocutaneous forearm flap seems to be the most ideal method when the bone defect is not bigger than 6-8 cm and only the replacement of mucosa is required. PMID- 1303884 TI - [Postgraduate dental education in Europe and America]. PMID- 1303885 TI - [Preparing dental radiographs without film. Radiovisiography]. AB - In dental practice it was with the Radiovisiography system that a dental X-ray picture can be made without film and development time. The radiation load of patients decreases from 62%- to 94% compared to dental film. The regulation of the contrast and the light intensity of the electronic picture makes the further evaluation of the exposure possible. PMID- 1303886 TI - [Toxicological implications of amalgams]. AB - Nowadays hard attacks have been launched by the media against the use of dental silver amalgams. Different diseases are attributed to dental amalgams mostly because of their mercury contents. These claims are based mainly on suppositions without controlled scientific studies. The amount of mercury vapour from amalgam restoration achieves--not even in adverse conditions--the quarter of the daily mercury intake by food. Their total value which might be harmful to health is under the level approved by the WHO thus we don't have to deal with its effect. We can reduce the mercury evolved from amalgam restorations with gamma 2 phase free amalgam and capsule amalgam application. PMID- 1303887 TI - [Isolated aplasia of the upper cuspids and its orthodontic management]. AB - A multi-band appliance was used to space-closure after the deciduous canines were extracted. The upper first molars got a ring the other teeth direct brackets. The mesial movement was achieved with rubber band pull. PMID- 1303888 TI - [Free radial forearm flap in the reconstruction of the mouth floor after removal of a tumor by pull-through method]. AB - Free radial forearm flap was used to replace the tissue defect caused by pull through operation for cancer of the mouth in 13 cases. There was no total or partial flap failure. The greatest advantage of the method is that the restriction of the tongue movement is less when compared to the results of other methods since the thin forearm flaps are well adaptable and are of a pliable nature. The newly developed lower alveolar crest makes the prosthetic rehabilitation possible. PMID- 1303889 TI - [Remembering Prof. Bela Simon]. PMID- 1303891 TI - The association of 5' haptoglobin gene-flanking sequences with nuclear matrix proteins during the acute phase response. PMID- 1303890 TI - Regulation of mouse serum amyloid A3 gene expression during acute phase reaction. PMID- 1303892 TI - Studies of the DNA binding affinity of fetal rat liver nucleoproteins to the alpha 1-acid glycoprotein gene promotor. PMID- 1303893 TI - Acute phase reaction-related changes of nucleoproteins affinity for wheat germ agglutinin. PMID- 1303894 TI - Differential effect of interleukin-1 on interleukin-6-stimulated alpha-1 antichymotrypsin expression in human hepatoma cell lines. PMID- 1303895 TI - Glycated proteins as inducers of acute phase cytokines. PMID- 1303896 TI - Amyloidosis and the acute phase response. PMID- 1303897 TI - Novel saccharide ligands for serum amyloid P component. PMID- 1303898 TI - Molecular evolution and acute phase change of guinea pig contrapsin and alpha-1 antiproteinase. PMID- 1303899 TI - Interleukin-6 in vivo. PMID- 1303900 TI - Relevance of haptoglobin in clinical medicine. PMID- 1303901 TI - Regulation of hepatic lipid metabolism by cytokines that induce the acute phase response. PMID- 1303902 TI - Concentration of malondialdehyde in the serum of patients with rheumatoid arthritis. PMID- 1303903 TI - Genetical control on lentinan-induced acute phase responses and vascular responses. PMID- 1303904 TI - The influence of different forms of orosomucoid on immune reaction. PMID- 1303905 TI - New argument in favour of orosomucoid (OR) microheterogeneity investigation in oncological practice. PMID- 1303906 TI - Macrophage stimulation and proteinase/proteinase inhibitors balance during inflammation. PMID- 1303907 TI - Amidolytic activities in acetone-treated human plasma. PMID- 1303908 TI - [Evaluation of treating neonates with surfactants for respiratory distress syndrome. I. Importance of gas exchange]. AB - Twenty seven preterm babies enrolled in a European Multicentre Trial (Curosurf 4) were treated with surfactant Curosurf (Chiesi Farmaceutici, Italy). Mean gestational age was 30.7 weeks (range 26-36), and mean birthweight 1617 g (960 2790 g). Curosurf was given as a rescue therapy in babies with severe RDS between 2-72 hours after birth. Indications for treatment were: clinical and radiological diagnosis of RDS, need for mechanical ventilation and arterial to alveolar oxygen tension ratio < 0.22. Umbilical arterial catheterisation and written parental consent were obtained before trial entry. The results are given for all treated babies and have not been analysed according to the dose of Curosurf. In the first hour after treatment there were mean increases in PaO2 of 27.4 mm Hg (3.6 kPa), and oxygen saturation of 8.2%, a mean decrease in PaCO2 of 15.0 mm Hg (3.3 kPa) and mean increases a/A ratio of 0.1. It was possible to reduce mechanical ventilation one hour after Curosurf instillation: inspired oxygen concentration was decreased by a mean of 12.3%, peak inspiratory pressure by 4.3 cm H2O, and frequency by a mean of 5.6 per minute. It is concluded that there are immediate beneficial effects of Curosurf in preterm babies with severe RDS. PMID- 1303909 TI - [Evaluation of pulmonary flow through the aortic and pulmonary valves of the fetus during normal pregnancy from 20 to 41 weeks of gestation with two dimensional doppler (2dd)]. AB - Doppler data have been analysed in 49 cases for aortic valve and 35 cases for pulmonary valve. For both valves V max, V mean, Aortic Flow and Pulmonary Flow were measured and compared with gestational age. RESULTS: V max A = 0.85 +/- 0.23 m/s, V max P = 0.72 +/- 0.14 m/s, (p < 0.01); V mean A = 0.28 +/- 0.08 m/s, V mean P = 0.24 +/- 0.06 m/s, (p < 0.02); A Flow = 699 +/- 285 ml/min, P Flow = 740 +/- 310 ml/min, and 275 +/- 100 ml/min/kg for aortic valve and 322 +/- 120 ml/min/kg for pulmonary valve (p > 0.05). There was statistical significant correlation between aortic and pulmonary flow and gestational age and there was no correlation between max velocity and gestational age for these valves. PMID- 1303911 TI - [Kidney function in pregnant women with hypertension in the course of chronic kidney disease]. AB - In 53 pregnant patients in the III trimester of pregnancy kidney function investigations were carried. The group consisted of 23 patients with chronic kidney diseases with superimposed arterial hypertension (examined group) and of 30 healthy pregnant women (control group). In the examined group an increase of blood-serum urea, uric acid and creatinine concentrations were demonstrated. In these women the blood pH was decreased also. The urinary excretion of NH4+ and H+ ions was decreased, the excretion of Na+ and K+ was normal. PMID- 1303910 TI - [Kidney function in pregnant women with primary arterial hypertension]. AB - Investigations covered 64 women in the III trimester of pregnancy. In this group 34 were with diagnosed primary arterial hypertension (examined group), and 30 were apparently healthy (control group). In both groups the blood serum concentrations of creatinine, urea, uric acid and electrolytes were determined. Creatinine clearance and acid-base balance were determined in these cases also. In 24 hours urine samples the NH4+, H+, Na+ and K+ ions concentrations were established. Impaired kidney function was shown in the patients from the examined group. PMID- 1303912 TI - [Alpha-amylase in serum and urine of women with hypertension during the III trimester of pregnancy]. AB - The urinary and blood serum activity of alpha-amylase was tested in 34 women with arterial hypertension in the III trimester of pregnancy (examined group). The results were compared with a control group of healthy women (35 urine samples and 108 blood-serum samples). In both groups other biochemical examinations were carried additionally (the serum creatinine, urea, uric acid, electrolytes and the acid-base balance levels were established). In the examined group an increased activity of the alpha-amylase in the blood serum was demonstrated. PMID- 1303913 TI - [Activity of alpha-amylase in serum and urine of pregnant women with diabetes mellitus type I]. AB - The investigations covered 33 women in the III trimester of pregnancy with diagnosed, insulin-dependent diabetes mellitus, and 108 healthy women in the control group. The alpha-amylase activity was measured in the blood-serum and urine samples using the Caravay technique. An increased activity was demonstrated in the blood-serum samples in the examined group. The values were not related to the levels of glycemia. The urinary alpha-amylase activity was similar to that in the control patients. No coincidence between the activity and glycemia or acetone levels could be demonstrated. PMID- 1303914 TI - [Threats of infectious factors in the uterine neck regarding chlamydia trachomatis in imminent premature deliveries]. AB - The research concerned threats of infections factors to a endocervix in imminent premature deliveries. It was ascertained that Chlamydia (C) trachomatis is the most frequent pathogenic factor, which occurred in 41.8% of cases. The premature delivery occurred in 16.3% of women with positive C. trachomatis test results. PMID- 1303915 TI - [Levels of thyroid hormones and thyrotropic hormone in serum of women with perimenopausal arterial hypertension]. AB - Test carried out in 96 women aged between 43 to 55 years (50.46 +/- 4.7), who did not take any drugs during the last 3 months. The women were divided into two groups: premenopausal and early postmenopausal. Each group was subdivided according to blood pressure: with normal pressure and with arterial hypertension. The concentration of T4, T3 and TSH were measured using a radioimmunologic method. The saturation of carrier proteins was established with the T3/test, the result of which was used to divide T4 and T3 and to obtain FT4I and FT3I respectively. It was found that women with arterial hypertension have significantly higher (p < 0.001) TSH concentration. The concentration T3 and FT3I were significantly higher (p < 0.01) in women with arterial hypertension in the postmenopausal period. PMID- 1303916 TI - [Excretion of free catecholamines in urine and activity of some enzymes involved in catecholamine metabolism with arterial hypertension during menopause]. AB - This study was performed in 60 women aged between 47-55 years (mean age 50.46 +/- 1.7), divided into two groups: premenopausal and postmenopausal. Each group was subdivided according to arterial pressure: with normal pressure and arterial hypertension. Daily urinary excretion of catecholamines was determined according to method of Euler and Lishajko, the activity of dopamine--beta-hydroxylase in serum according to Nagatsu et al. The activity of catechol-O-methyltransferase in erythrocytes according to Axelrod et al., the activity monoamineoxidase in serum according to Wurtman et al. Daily urinary excretion of vanilmandelic acid determined according to Pisano et al. It was found that women with menopausal arterial hypertension have significantly greater urinary excretion of adrenaline and noradrenaline (p < 0.001) in the premenopausal period, and adrenaline (p < 0.01) in the postmenopausal period. The activity of dopamine-beta-hydroxylase did not differ from the control group. The activity of COMT in erythrocytes of women and MAO in serum of women with menopausal arterial hypertension was significantly lower. Daily urinary excretion of vanillinmandelic acid in women with menopausal arterial hypertension was significantly lower. PMID- 1303917 TI - [Changes of pituitary hormone concentration during vasomotor disorders, in blood serum of women during the early phase after surgical castration]. AB - The behaviour of the concentration of the selected pituitary hormones during hot flushes at women after a surgical castration was evaluated. The inquiry concerned 42 women 46.7 +/- 3.4 years old, with a regular menstruation till the hysterectomy and the adnexectomy due to sexual organs diseases. The inquiry contained a determination, by means of radioimmunological methods, of the concentration of the hormones: LH, FSH, PRL, HGH, TSH in the blood serum taken at women 48 hours before the operation, on the 8th day after the intervention and 5 min after the hot flushes apparition. At the same time, the finger skin temperature and the pulse rate was taken. The rise in the finger skin temperature by 1.2 degrees C and the mean rise in the pulse rate by 11.3 beats/min during hot flushes were noticed. An important increase of the LH and HGH concentration during hot flushes was also observed. PMID- 1303918 TI - [Myomectomy through the vagina--routine treatment or still a rarity?]. AB - The description and initiation of a method of myomectomy through vagina at 12 women in reproductive age has been done. In succeeding steps of operation special attention on difficulties and facilities during these surgical interventions has been made. Myomectomy through vagina shortened the time of the operation diminished the loss of blood and postoperative complications. The postoperative cicatrix on the abdominal wall has not been left by this method of operation. PMID- 1303919 TI - [Clinical picture of tumors from the mesoblastoma group in women]. AB - Yolk Sac Tumor (YST) originating from the primitive reproductive cells reminds with its microscopic construction a gallbladder or an endodermal sinus thus the name endodermal sinus tumor, Yolk sac tumor, mesoblastoma vitellinum Teilum. There have been presented here two cases of YST of different locality with unusual development of one of them and rapid course in the both cases. In both discussed cases the survival period exceeds 3 months. Both patients are still alive and the period from the day of diagnosis and operation is in one case 26 months and in the second one 11 months. PMID- 1303920 TI - [The management of subarachnoid hemorrhage in pregnancy]. AB - Subarachnoid haemorrhage (SAH) from an intracranial aneurysm or arteriovenous malformation is a grave complication of pregnancy. Authors critically analyzed 12 cases of verified SAH during pregnancy from an 11 identified and 1 unidentified cerebral vascular malformation. Aneurysms were responsible for SAH in 7, and arteriovenous malformations in 4 patients. Subarachnoid haemorrhage occurred during I trimester in 2, II trimester in 3, III trimester in 6 patients and after cesarean delivery in 1 case. We conclude that the decision to operate after SAH during pregnancy should be based upon neurosurgical principles, whereas the cesarean delivery should be done in every pregnant patient with SAH. PMID- 1303922 TI - [Pharmacokinetic investigations of verapamil used as a concomitant drug in treatment of premature labor]. AB - The study carried out on 35 pregnant women, who were threatened with fenoterol and verapamil by premature delivery. The pharmacokinetics of verapamil have been examined after single dose and in steady state using drug in a dose of 2 x 80 mg/day (15 women) and 3 x 40 mg/day (8 women). Verapamil in a dose of 2 x 80 mg/day induced average steady state concentration in range of 40.6 +/- 7.8 ng/ml to 134.2 +/- 56.9 ng/ml and in a dose of 3 x 40 mg/day 28.9 +/- 5.1 ng/ml to 69.8 +/- 11.2 ng/ml. Since most authors take as optimal therapeutic level of verapamil in blood the range of 100-200 ng/ml, it seems that dosage regimen of 2 x 80 mg/day can be recommended. Additionally, verapamil concentration in maternal blood and in amniotic fluid were determined simultaneously in a group of 12 pregnant women. Verapamil readily penetrates placenta reaching in amniotic fluid about 70% of the concentration observed in maternal blood. PMID- 1303921 TI - [Pharmacokinetic examination of theophylline in pregnancy in cases of fetal anoxia]. AB - The purpose of the investigation was to determine the effects of pregnancy on theophylline pharmacokinetics and to clarify the clinical effect of theophylline treatment in cases of threatened anoxemia of foetus. The study was carried out in 15 pregnant women between 28 and 32 weeks of pregnancy with chronic anoxemia of the foetus. The women obtained Aminophyllinum "Polfa" 250 mg (201.3 mg of theophylline) every 12 hours for 4 days to achieve the steady-state of theophylline. After the first dose the drug concentration reached the level of theophylline in range of 12.05 +/- 4.57 micrograms/ml in 15 minutes to 3.62 +/- 0.74 micrograms/ml in 12 hours. The subsequent doses increased the concentration and in steady-state the concentration fluctuates between 21.48 +/- 10.00 micrograms/ml and 6.20 +/- 1.56 micrograms/ml, what coincides with established therapeutic range of theophylline (10-20 micrograms/ml). Elimination of the drug was characterised by calculation of the elimination rate constant and drug clearance. Both parameters are higher after a single administration what suggest the accumulation of theophylline after multiple drug administration by the saturation of enzymes taking part in metabolism of the drug. Attention should be paid higher values of half-life in pregnancy in comparison with those obtained previously in healthy volunteers. Comparative investigations of the level of theophylline in amniotic fluid in relation to maternal blood in steady-state showed a high correlation between these two values (r = 0.7867, p < 0.006). The proportion of the concentration of theophylline in relation to that in maternal blood is about 60% (0.5978 +/- 0.1599).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1303923 TI - [Use of GnRH analog for induction of gonadotropin ovulatory surge in cycles stimulated by clomiphene citrate and menopausal gonadotropin in an in vitro fertilization program]. AB - In 23 women treated for sterility by the in vitro fertilization method the gonadotropins ovulatory surge was stimulated by applying a GnRH analogue (Busereline). The authors showed that a single injection of GnRH analogue in the cycles stimulated with clomiphene citrate and menopausal gonadotropin causes pituitary output of both LH and FSH which is sufficient for morphological and functional maturity of the oocytes. After such treatment two patients conceived and delivered healthy babies. PMID- 1303924 TI - [Production of progesterone in short term tissue culture by follicular cells of women]. AB - After volume and content of the follicular cells were determined the concentration of LH, FSH and prolactin was estimated in the ovarian follicular fluid taken during laparotomy of 17 women (ages 14-43). The sixty six hour follicular fluid cells cultures were established and the concentration of the medium progesterone were assessed by means of radioimmunological methods. The ability of cells to produce progesterone was demonstrated in 3/4 of the cases. It has been found that the progesterone producing cells come from the follicles with significantly higher LH and prolactin concentration. The positive correlation was observed between FSH concentration in follicular fluid and culture progesterone production by the cells in 42 and 66 hour of the experiments. PMID- 1303925 TI - [Surgical treatment of polycystic ovary syndrome. A. Preoperative examinations]. AB - The aim to study was the determination the effect of operative treatment of 31 patients with polycystic ovary syndrome. Before the operation primarily the authors confirmed at the patients the presence of menstrual abnormalities in 96.8%, of infertility in 100%, of hirsutism I. in 9.7%, II. in 61.8%, III. in 29% and the average level of 17-ketosteroids 16.0 +/- 6.9, of DHEA 3.7 +/- 1.5 mg and of estrogens 39.0 +/- 15.1 mcg in 24 urine, of total testosterone 0.98 +/- 0.24, of FSH 3.4 +/- 1.5, of LH 44 +/- 2.4, of prolactin 11.4 +/- 5.4 and of estradiol 0.32 +/- 0.35 ng/ml in blood. On the basis of clinical, hormonal or/and ultrasonographic examinations the diagnosis of the polycystic ovarian disease was performed. PMID- 1303926 TI - [Surgical treatment of polycystic ovary syndrome. B. Postoperative examinations]. AB - After the wedge resection of the ovaries the authors obtained the normal menses in 100%, the reduction of total testosterone in blood of 41.8% and of 17-KS in urine of 20%, an increase of fertility of 62.5% and in hirsutism a correction only of 12%, the stopping of 12% and no correction of 76%. The authors conclude that the cause of the healing or of the correction is placed in the resection of 3/4 of the changed ovaries with cysts follicles with distinct thecal layer what is accompanied by the reduction of testosterone on average of 41.8%. On contrary a weak correction in hirsutism has the explanation that the existent hirsutism is supported even by the normal level of testosterone in organism. PMID- 1303928 TI - [Uroflowmetry in diagnosis of urinary stress incontinence in women]. AB - The authors' aim was to evaluate the range of uroflowmetry in diagnostics of stress urinary incontinence (sui) in women. The examinations were carried out in 59 women with sui, aged from 35 to 45 years (group I). The control group consisted of 20 asymptomatic women (group II). To evaluate volumes of urine voided during micturition in a unit of time a urological flowmeter UF-1 (produced by COTM, Bialystok) was used. Numeric data of flow were analysed, as well as registered curves of flow were ascribed to one of the following flow patterns: normal, multi-peak or interrupted. The conducted studies revealed statistically significant differences in flow values in group I, compared to group II. A more frequent incidence of multi-peak and interrupted flow patterns was found in women with sui, which could be related to a neurogenic component in etiology of the disease. PMID- 1303927 TI - [FAI in hirsutism of women with polycystic ovary syndrome]. AB - The free androgen index (FAI) was estimated and compared with intensiveness of hirsutism in ten anovulatory women of reproductive age referred for polycystic ovarian syndrome with LH/FSH ratio greater than 3.0. The control group consisted of five ovulatory women. The serum testosterone, SHBG, LH and FSH were measured by radioimmunoassay. The mean plasma level of hormones in the study group was following: T-5.8 +/- 1.9 nmol/l, SHBG - 51.0 +/- 18.0 nmol/l, LH - 18.5 +/- 6.0 mIU/ml, FSH - 5.0 +/- 1.2 mIU/ml, in comparison with the control group: T - 1.4 +/- 0.4 nmol/l, SHBG - 90.0 +/- 11.2 nmol/l, LH - 9.4 +/- 4.8 mIU/ml, FSH - 7.3 +/- 0.9 mIU/ml. FAI was calculated as T/SHBG ratio multiplied by 100. In contrast to the control group the seven times higher FAI did not accompany the intensiveness of hirsutism. PMID- 1303929 TI - [Antioxidant agents--importance in neonatology]. AB - The toxic consequences of oxygen therapy may be development some neonatal diseases, for example: retrolental fibroplasia and bronchopulmonary dysplasia. It's now generally believed that oxygen induced cell toxicity is the result of formation of highly reactive free radicals. The greater incidence of these disorders in preterm infants suggest that some aspect of prematurity increases susceptibility of effects of toxic oxygen species. It's proposed the term for these disorders: "oxygen radical diseases of prematurity". Verification of the hypothesis about role of the antioxidant defense mechanisms of neonate may have important implications in the pursuit of the etiology these diseases and in identification of agents that may minimize toxicity associated with oxygen therapy. PMID- 1303931 TI - Cadmium in the human environment: toxicity and carcinogenicity. Symposium proceedings. Gargnano, Italy, September 1991. PMID- 1303930 TI - [Late vesico-vaginal fistula after colporrhaphy for urinary incontinence]. AB - We present a case of a 65 year-old woman with a late vesicovaginal fistula after colporrhaphy. Too late proper diagnosis of that complication caused perivesical tissue inflammation and led to damage to the urinary bladder, occlusion of the urethra as well as created a massive inflammatory tumor in the minor pelvis, which suggested a cancerous process. Bilateral hydronephrosis forced us to make bilateral nephrostomy. After intensive antiinflammatory therapy, anterior exenteration and Bricker's operation were performed with a finally good effect. PMID- 1303932 TI - Factors influencing the cadmium body burden in a population study. AB - The cadmium body burden, as estimated from 24-h urinary cadmium (Cd-U), was determined in 1523 non-occupationally exposed subjects living in five areas of Belgium. It increased with age until 55-65 years in both sexes and thereafter decreased slightly. It was higher in smokers but was inversely associated with alcohol consumption and social class. In men only, it was also positively correlated with body mass index. After the menopause, women showed a significant increase in 24-h Cd-U independently of the other factors. In addition, the cadmium body burden was independently associated with place of residence in both sexes. Highest levels of Cd-U were found in subjects living in an area with soils heavily polluted by cadmium. PMID- 1303933 TI - Ten-year follow-up of biological monitoring of cadmium-exposed workers. AB - In this study, 105 workers exposed to cadmium for over 10 years were subjected periodically to environmental monitoring, biological monitoring and medical surveillance. They were divided into subgroups, one in which Cd-B and Cd-U exceeded 10 micrograms/l and 10 micrograms/g creatinine respectively and the other in which they were below these proposed biological exposure indices. Urinary beta 2-microglobulin was used as an indicator of tubular damage. Over the past 3 years 12 workers had raised urinary beta 2-microglobulin values (above 250 micrograms/l). Among workers with Cd-B and Cd-U levels always below the above limits, less than 3% had increased urinary excretion of beta 2-microglobulin, a percentage comparable with that of the reference population. When Cd-B exceeds 10 micrograms/l and Cd-U 10 micrograms/g creatinine on one or more occasions (although the median value still remains below this level), the frequency of tubular damage seems to be considerably higher (8.4 and 7.5% respectively). Thus the Cd-B and Cd-U limits proposed appear to be quite safe if strictly respected. However, median values appear too high to rule out the possibility of an increased incidence of tubular alterations. PMID- 1303934 TI - Integrated personal monitoring of cadmium exposure in Sweden. AB - Methods for the personal monitoring of human exposure to cadmium from air, food and beverages were studied in a group of 15 non-smoking women in Stockholm. Particles in the breathing zone air and duplicates of all food and beverages ingested were collected during seven consecutive days, as were faeces corresponding to the food ingested. Spot samples of blood and urine were also taken. The main sampling problems were caused by the noise of the personal air monitors and the short operation time of the batteries. On average, dietary cadmium (8.5 micrograms per day) contributed 99% of the total cadmium absorbed. There were large day-to-day variations in intake, most peaks corresponding to the consumption of seafood. Faecal cadmium was shown to reflect the total amount of cadmium ingested. There was a significant (p < 0.05) correlation between cadmium concentrations in blood (median 0.3 microgram/l) and average daily dietary intake of cadmium, but the blood cadmium levels could vary by a factor of four at one and the same average daily intake. The median urinary cadmium level was 0.2 microgram/l. PMID- 1303935 TI - Cadmium as an environmental hazard. AB - Cadmium occurs in nature at low concentrations, but human activities have caused cadmium contamination in all continents with the exception of Antarctica. In some areas, environmentally exposed humans have suffered kidney damage which has sometimes progressed to severe kidney failure and skeletal disease. In mammals and birds, cadmium accumulates in livers and kidneys at concentrations of 0.1-2 mg/kg and 1-10 mg/kg wet weight, respectively. Animals with a long life span such as horses have very high concentrations of cadmium in their organs: in renal cortex samples obtained from old horses, concentrations of nearly 200 mg/kg have been found. Histopathological examination of kidneys from environmentally exposed horses and certain species of sea birds have revealed morphological changes indicative of chronic interstitial nephritis. Remarkably high concentrations of cadmium (5-160 mg/kg) have recently been found in kidneys obtained from penguins living in Antarctica. The cadmium accumulation observed in animals living in Antarctica is unlikely to be the result of anthropogenic pollution. It shows how little we know and understand about the natural flow and behaviour of this elusive element in the ecosystems of the planet. PMID- 1303936 TI - Sources of cadmium, its distribution and turnover in the freshwater environment. AB - Cadmium enters the aquatic environment from numerous sources, e.g., via the atmosphere, from which the cadmium released by combustion, mainly of fossil fuels, is deposited. Since some fertilizers contain up to 40 mg/kg cadmium, wash out from agricultural land is another source. Zinc ores contain up to several percent of cadmium, and there may be high concentrations in raw zinc, zinc alloys and zinc compounds, so that cadmium may enter the aquatic environment from mining residues, solid wastes and wastewater discharges. Once in the aquatic environment, cadmium is highly mobile. Its dissolved species are extremely labile, and are the first to be released, e.g., when salinity increases in estuaries. Sediments reflect the metal loading in the past, and their analysis can be the key to an understanding of the fate of anthropogenic discharges into the hydrosphere. The internal cadmium loading of aquatic systems can be estimated from the remobilization rates of cadmium from sediments. PMID- 1303937 TI - Sources and pathways of cadmium in the environment. AB - Cadmium occurs naturally in rocks and soils, usually in concentrations of less than 1 microgram/g, but soils derived from some marine black shales and from rocks containing lead-zinc minerals frequently contain much larger amounts. These may lead to increased cadmium uptake by crops and vegetables grown for human consumption. Anthropogenic sources, including smelter emissions and the application of fertilizers and sewage sludge to land, may lead to contamination of both soils and crops. Regional cadmium enrichment or contamination of the surface environment can be delineated by geochemical surveys and by the compilation of soil inventories. The factors influencing the uptake of cadmium into food crops and the role of the atmosphere and soil as sources of cadmium in the diet and water supplies are discussed. No adverse health effects related to cadmium were found in an area where the cadmium intake of the local population was double the estimated United Kingdom average. PMID- 1303938 TI - Cadmium and health: the Belgian experience. AB - Studies in the 1970s on chronic cadmium poisoning in man in Belgium showed that the earliest effect was renal dysfunction with proteinuria. Subsequent studies were focused on the characterization of cadmium proteinuria, the diagnosis and prognosis of cadmium nephropathy and the assessment of the concentrations in urine and renal cortex leading to its occurrence. Chronic exposure to cadmium in industry gives rise to a proteinuria which may be tubular, glomerular or mixed in character. This proteinuria may be accompanied or preceded by a variety of other renal effects. In active male workers, three main groups of thresholds for urinary cadmium have been identified for the induction of these effects with corresponding thresholds in the renal cortex. However, these estimates probably cannot be extrapolated to the general population exposed to cadmium mainly by the oral route. The results of a large-scale cross-sectional study (Cadmibel) suggest that subclinical changes in tubular function may occur in the general population above a threshold of urinary cadmium as low as 2 micrograms/24h. PMID- 1303939 TI - Estimation of dietary intake of cadmium: reliability of methods. AB - The reliability of intake studies depends on representative sampling of foods, quality assurance of analytical methods, selection of adequate food consumption data and combining concentrations of heavy metals in foods with food consumption figures. The food balance sheet is usually unsuitable for intake estimations of cadmium, since it covers mainly unprocessed food and does not include individual food consumption data. The reliability of household surveys could be improved by taking food wastage into account, more detailed description of meals eaten outside the home, and calculating per capita consumption figures. The duplicate portions method seems to be the most reliable of the available techniques, but does not provide realistic information on variations in long-term intake, for which dietary surveys, food recall studies or food frequency questionnaires should be used. The duplicate portions technique is suitable for studies of risk groups. The average intake of cadmium in Finland is about 10 micrograms per day, but 5-10% of the population ingests more than 20 micrograms of cadmium per day. Additional exposure from smoking, ambient air and drinking-water considerably increases the variation in exposure. PMID- 1303940 TI - Factors affecting the intestinal uptake of cadmium from the diet. AB - Human data on the effects of diet composition on intestinal cadmium uptake are almost completely lacking but animal experiments indicate that it may profoundly influence the intestinal uptake of ionic cadmium. Thus, rats and mice fed human dietary items absorbed 5-8 times more cadmium than animals fed ordinary rodent pellets. All the data currently available indicates that, both in humans and in experimental animals, the bioavailability of dietary cadmium is not very different from that of ionic cadmium. However, diet composition may markedly affect the uptake of the latter. Accordingly, a valid assessment of the bioavailability of cadmium can be made in experiments where ionic cadmium is administered mixed with the diet. It is important, however, to discriminate between diet composition at the time of administration and dietary status. A better understanding of the factors affecting intestinal cadmium uptake is necessary in assessing the risk associated with dietary cadmium exposure and further studies are therefore urgently needed. PMID- 1303941 TI - Pulmonary deposition, clearance and effects of inhaled soluble and insoluble cadmium compounds. AB - The factors affecting the deposition of inhaled cadmium particles in different regions of the respiratory tract are discussed. The retention kinetics of inhaled cadmium compounds is determined by the various clearance processes. It is necessary to differentiate clearly between in vitro (water) solubility and in vivo (lung) solubility. Thus both cadmium oxide and cadmium sulfide particles are rather insoluble in water but the former are readily solubilized in the lung while the latter are cleared mainly by mechanical transport via alveolar macrophages. The pulmonary retention half-times of inhaled cadmium compounds are longer by approximately a factor of ten in primates than in rats. Acute pulmonary inflammatory effects of inhaled cadmium compounds are related to their in vivo solubility, and an approximately 10-fold higher dose of cadmium sulfide as compared with the chloride or oxide must be administered to the lung to elicit the same inflammatory response. Differences in biological effects may also exist with respect to the chronic effects of inhaled cadmium compounds, e.g., the pulmonary carcinogenic potency of inhaled cadmium sulfide may be less than that of other cadmium compounds. PMID- 1303942 TI - Occupational exposure to cadmium and lung function. AB - A total of 69 male subjects occupationally exposed to cadmium fumes in a factory producing silver-cadmium-copper alloys for brazing, were subjected to lung function tests, including ventilation (FVC and FEV1), residual volume (RV) and alveolar-capillary diffusion capacity (TLCO and KCO). For each subject, the cumulative exposure to cadmium was calculated as the product of the number of years in the job and the average atmospheric concentration of cadmium (expressed in micrograms/m3) encountered each year. Cadmium-exposed subjects had moderately higher mean values of RV (+ 8%) as compared with the control group; the increase was greater (+ 10%) in the subgroup of workers with greater cumulative exposure to cadmium. No significant differences were observed in FVC, FEV1, TLCO and KCO. PMID- 1303943 TI - Metallothionein: analysis in tissues and toxicological significance. AB - The chemical forms of cadmium in tissues can be largely divided into two groups, namely metallothionein (MT)-bound and non-MT-bound. Cadmium accumulates in the body mainly as the former, while the latter, the toxic form of cadmium, can be detected typically in tissues in two cases: (i) before induction of sufficient amounts of MT to sequester cadmium; and (ii) after the accumulation of cadmium in amounts such that it is beyond the capacity of the organ concerned to synthesize enough MT. We identified alcohol dehydrogenase as the major cadmium-binding protein in the liver before induction of MT, though the enzyme activity was not affected by such binding in vivo. The capacity to synthesize MT can be determined from the relative ratio of cadmium to co-existing metals (zinc and copper) in MT, and also by the increase in cadmium in the non-MT-bound form that follows the increase in this ratio. Non-MT-bound cadmium can be detected selectively by a histochemical method using a chelating agent, thiazolylazonaphthol. PMID- 1303944 TI - Differences in chromatographic behaviour of rat and pig metallothionein isoforms: a possible method of distinguishing between exogenous and endogenous metallothioneins. AB - Part of the exogenous metallothionein present, e.g., in food of animal origin, can survive gastrointestinal digestion, and will be selectively taken up in the kidneys. The present paper describes a possible method of distinguishing exogenous cadmium metallothionein (CdMT) from its endogenous counterpart. Rat and pig metallothionein were purified from liver and kidneys of animals previously injected with cadmium chloride. In rats cadmium was present in two MT isoforms, RMT-1 and RMT-2. Ion-exchange chromatography of porcine liver cytosol also showed that two isoforms existed, but a major portion of the cadmium elutes with the second isoform, VMT-2. Using a reversed-phase HPLC system, the purified rat metallothionein isoforms eluted as single peaks before pig MT isoform VMT-2. The difference in chromatographic behaviour on reversed-phase HPLC between species specific metallothioneins offers a unique possibility to study the fate of endogenous and exogenous metallothioneins simultaneously. This will be illustrated by the redistribution of 109Cd from exogenous CdMT to endogenous CdMT after intravenous injection of VMT-2 into rats. PMID- 1303945 TI - Endogenous intestinal metallothionein possibly contributes to the renal accumulation of cadmium. AB - At low levels of dietary cadmium chloride, cadmium accumulates directly in the kidneys and not in the liver. As dietary cadmium induces intestinal metallothionein (MT), intestinal CdMT complexes could be at least partly responsible for the renal accumulation of oral cadmium. For this to be possible, however, serosal release of mucosal CdMT would be required. To test this hypothesis, we perfused isolated rat small intestinal segments (Fisher-Parsons method) in an attempt to demonstrate the release of intestinal MT. After two weeks of feeding dietary cadmium chloride, intestinal MT was induced in amounts proportional to the dietary cadmium level. Subsequent in vitro perfusion of the small intestine revealed a concentration-dependent release of intestinal MT on the serosal side. When 109CdCl2 was present in the perfusion medium, 109Cd appeared on the serosal side mainly in the MT fraction. These results indicate that endogenous intestinal MT may deliver CdMT to the organism, thus possibly contributing to the renal accumulation of orally ingested cadmium. PMID- 1303947 TI - Role of metallothionein in human placenta and rats exposed to cadmium. AB - A strong positive relationship between zinc and copper and metallothionein (MT) in placentas has been found, but a negative one between cadmium and MT. In rats given cadmium i.p. as the chloride, liver cadmium is lower and kidney cadmium higher than in cadmium-treated non-pregnant rats, suggesting that pregnancy enhances mobilization of cadmium from liver to kidney. The cadmium concentration of digested whole fetuses is not significantly increased in offspring of dams given cadmium i.p. as the chloride or CdMT, but the placental levels of cadmium and MT are increased. The placenta therefore acts as a barrier to maternal-fetal cadmium transfer. The way in which cadmium is retained in the placenta but zinc and copper are transferred to the fetus is not understood, since all are bound to MT. Focal renal tubular necrosis and placental necrosis occur at the same level of cadmium exposure, suggesting a similar threshold to cadmium toxicity for the two organs. PMID- 1303946 TI - Metallothionein and tissue damage. AB - Metallothioneins (MTs) are a class of small cysteine-rich heavy metal binding proteins produced in response to a variety of stresses, inflammation, and as components of the acute-phase response. Although the exact role of MT in this phase is not known, a number of reports have shown that expression of hepatic MT is markedly increased in response to bacterial infection, an effect mediated by lipopolysaccharides. More recently, it has been suggested that MT may play a major role in the prevention of tissue damage. Thus MT has been shown to be an efficient free radical scavenger. Indirect activation of macrophages and neutrophils during the acute phase of inflammation result in a massive release of various species of oxygen metabolites which may be indirectly responsible for the initiation of apoptosis. In addition, expression of MT also increases cell resistance to radiation damage. Together, these results suggest that MT could be part of a generalized protective system in mammalian cells. PMID- 1303948 TI - Teratogenicity of cadmium chloride in the South African frog, Xenopus laevis. AB - The teratogenicity of cadmium chloride was tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure. In five assays, groups of Xenopus embryos were grown in media containing concentrations of 0.75-56 mumol/l; controls were incubated in medium without cadmium chloride. Exposures began 5 h post-fertilization and ended 101 h post-fertilization. In control groups, > 95% of embryos survived at 101 h and the incidence of malformations was < 7%. In Cd(2+)-exposed groups, concentration-dependent mortality and numerous malformations were observed, including gut malrotation, ocular anomalies, bent notochord, misshapen fin, facial dysplasia, cardiac deformities and dermal blisters. Other abnormalities included stunted growth and hypopigmentation. The minimum concentration of cadmium chloride that inhibited growth was 18 mumol/l. The median embryolethal concentration (LC50) was 32 (SE +/- 4) mumol/l; the median teratogenic concentration (EC50) was 3.7 (SE +/- 1) mumol/l; the teratogenic index (TI = LC50/EC50) was 8.6. This study demonstrates that cadmium chloride is teratogenic for Xenopus laevis and provides a standardized experimental model for studying the molecular mechanisms of cadmium teratogenesis. PMID- 1303949 TI - Birth weight of children and cadmium accumulation in placentas of female nickel cadmium (long-life) battery workers. AB - In a retrospective epidemiological study on the birth weight of 266 children of 137 female workers in a nickel-cadmium battery factory, 157 children of workers occupationally exposed to cadmium were compared with 109 born to non occupationally exposed workers. No effect of cadmium exposure on birth weight was detected, but a statistically significant effect on birth weight of smoking during pregnancy was observed. In a prospective study on the same population of female battery workers, 27 placentas were collected and the cadmium distribution and concentration in tissue subsamples determined. Placental cadmium concentrations were positively correlated with maternal blood cadmium. The cadmium concentration in placentas ranged from < 0.002 to 0.095 microgram/g (wet weight), the mean concentration +/- SD was 0.021 +/- 0.022 microgram/g (wet weight). Morphological and ultrastructural studies of placental tissues did not reveal any effect of cadmium. This study did not provide any evidence in support of the hypothesis that the placenta may be the critical organ in exposure to cadmium. PMID- 1303950 TI - Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study. AB - This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden. PMID- 1303951 TI - The role of Ca2+ in cadmium-induced renal tubular cell injury. AB - Changes in rat renal proximal tubule cell gene expression were studied in vitro using a cadmium metallothionein (CdMT) exposure model. Increased expression of MT together with alterations in the expression of several other stress protein products were demonstrated by 35S-two-dimensional gel electrophoresis. Stress proteins with estimated molecular masses of 32, 70 and 90 kDa were observed to be increased after 4 h of exposure. These changes preceded the onset of cell injury. Internal stores of Ca2+ were not found to be measurably altered, as measured by the changes in fluorescence of the dye FURA-2. These data suggest that the observed alterations in gene expression are directly mediated by Cd2+ and not secondary to increased availability of Ca2+ within the target cell population, perhaps mediated by the transacting factor which regulates MT synthesis. The calcuria resulting from in vivo exposure to Cd2+ in workers or CdMT exposure in animal models may be secondary to alterations in renal proximal tubule cell gene expression. PMID- 1303952 TI - Cadmium-induced bone loss: increased susceptibility in female beagles after ovariectomy. AB - Bone resorption, as measured by release of bone 45Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/l cadmium in drinking water. The 45Ca response was greater in ovariectomized animals than in sham operated controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood cadmium concentrations were 3-8 micrograms/l during the earliest bone resorption response and 13-15 micrograms/l at the end of the study. During seven months of cadmium exposure, bone mineral densities decreased most in the ovariectomized animals exposed to cadmium: -15.4 +/- 4.3% for the tibia distal end and -7.2 +/- 1.2% for the lumbar vertebrae (L2-L4) (mean +/- SE, n = 4). The results indicate that cadmium may act directly on bone and that postmenopausal women exposed to cadmium in industry or via cigarette smoke may be at increased risk of cadmium-induced bone loss. They also support a direct role of cadmium in the etiopathology of itai-itai disease among postmenopausal women in Japan. PMID- 1303953 TI - Placental transfer of cadmium. AB - Cadmium levels in blood have been determined in mother-newborn pairs from the surroundings of a copper smelter and a control area in Northern Sweden. The smelter's cadmium emissions to the air have decreased substantially since the 1970s, and in 1989 the emission was one ton. Venous blood was sampled from the mothers during delivery and from the umbilical cords, and analysed for cadmium by flameless atomic absorption spectrophotometry. There were no significant differences in cadmium levels, as between exposed women and controls, and blood levels were low, even in an industrial area. The most important environmental exposure seemed to be smoking. There was, however, a significant increase in cadmium levels during pregnancy among non-smoking women in both groups, p < 0.01. The cadmium levels in the newborn babies were about 70% of those in the mothers. Cadmium levels in the babies of non-smoking mothers were significantly higher in the vicinity of the smelter than in the control area (p < 0.05). PMID- 1303954 TI - Cadmium, metallothionein and renal tubular toxicity. AB - Cadmium-induced nephrotoxicity develops at cadmium concentrations in the renal cortex of 10-300 micrograms/g wet weight. The actual concentration at which it develops depends on a number of factors, e.g., exposure route, chemical species of cadmium administered, rate of administration and simultaneous exposure to other metals. The role of these factors can be explained by a mechanism of cadmium nephrotoxicity in which both extracellular and intracellular metallothionein binding play an essential role. In reindeer used for human food, cadmium was shown to be bound to metallothionein-like proteins. If cadmium bound to such proteins enters the blood plasma via the gastrointestinal tract, this is of special toxicological significance. Metallothionein-bound cadmium in the plasma of experimental animals is efficiently transported to the kidney. Tubular dysfunction in the kidney following a normally tubulotoxic dose of cadmium bound to metallothionein was prevented by preinduction of metallothionein synthesis by small non-toxic doses of cadmium. PMID- 1303955 TI - Application of the 'critical effect' and 'critical concentration' concept to human risk assessment for cadmium. AB - Exposure to cadmium can give rise to a number of adverse health effects. In human risk assessment it is important to identify effects that occur at relatively low exposures, i.e., the critical effects, which are crucial for preventive action. The effect of cadmium on the kidney, namely, tubular dysfunction, has been regarded as the critical effect in long-term human exposures. Quantitative dose response data can be derived from a risk model based on metabolic parameters and observed relationships between cadmium concentrations in the renal cortex and the occurrence of proteinuria in industrial workers. There is reasonable agreement between this model and epidemiological observations. Low-dose-low-incidence extrapolations have been made based on this model. However, experimental and epidemiological studies are providing increasing evidence that cadmium is carcinogenic and this serious effect, considered to be stochastic in character, may reasonably be considered as a critical effect. A quantitative evaluation is difficult with the available data. The preventive action usually taken for substances which are considered to be carcinogenic is to limit the use of and exposure to cadmium as much as possible, thus achieving exposure levels for cadmium lower than those giving rise to kidney damage. PMID- 1303956 TI - Mechanism and epidemiology of bone effects of cadmium. AB - A slow epidemic of a combination of osteomalacia and kidney damage (itai-itai disease) was first noted in Japan in the late 1940s. During the same period reports of severe bone effects in cadmium-exposed workers in some European factories were published. Cadmium-induced kidney effects and their connection with bone effects were first reported in 1950. Epidemiological and clinical studies in Japan since 1962 have shown that the bone effects develop only at very high cadmium exposures and that persons with low intakes of calcium or vitamin D are particularly at risk. Animal experiments have confirmed that cadmium induces bone effects at high exposures. Six possible mechanisms may explain the cadmium induced bone effects: (1) interference with parathyroid hormone (PTH) stimulation of vitamin D production in kidney cells; (2) reduced activity of kidney enzymes activating vitamin D; (3) increased excretion of calcium in urine; (4) reduced absorption of calcium from intestines; (5) direct interference with calcium incorporation into bone cells; and (6) direct interference with collagen production in bone cells. The high cadmium exposures needed to produce bone effects may still occur in developing countries, where many people have poor nutritional status and could be vulnerable to such effects. PMID- 1303957 TI - Dose-response relationship for renal dysfunction in a population environmentally exposed to cadmium. AB - Two epidemiological studies aimed at investigating the dose-response relationship of environmental cadmium exposure were performed in a population living in the Kakehashi River basin, a cadmium-polluted area in Japan. In the first, the average cadmium concentration in rice from each village was used as an indicator of exposure and metallothioneinuria or beta 2-microglobulinuria as an index of renal tubular dysfunction. Dose-related increases in both the latter indices were observed. The total cadmium intake resulting in both metallothioneinuria and beta 2-microglobulinuria was calculated to be approximately 2 g for both sexes. In the second study, the dose-response relationship between urinary cadmium and metallothioneinuria or beta 2-microglobulinuria was evaluated in the same population. Prevalence rates increased proportionally with increasing urinary cadmium (Cd-U). The values of Cd-U corresponding to the prevalence rates of metallothioneinuria in the non-exposed population were calculated to be 4.2 micrograms/g creatinine for men and 4.8 micrograms/g creatinine for women; for beta 2-microglobulinuria the corresponding figures were 3.8 micrograms/g creatinine for men and 4.1 micrograms/g creatinine for women. PMID- 1303958 TI - Integrated index of occupational exposure to cadmium as a predictor of kidney dysfunction. AB - In a study carried out in an alkaline battery factory, the study group consisted of 141 factory workers exposed to cadmium, while 206 workers in the textile industry constituted the control group. Cadmium in blood (Cd-B), cadmium in urine (Cd-U) as well as beta 2-microglobulin and retinol-binding protein (RBP) in urine were determined. Exposure to cadmium in the factory was high. In 1988, Cd-B concentrations in different departments averaged 11.2-29.9 micrograms/l. To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index [Cd-B (micrograms/l) x years of exposure] is proposed. According to the dose-response relationship, an increase in low molecular weight protein excretion in urine can be expected in 10% of subjects at an integrated exposure index of about 300 micrograms/l x years of exposure. The data obtained confirmed the validity of the recommended health-based limits for occupational exposure of 10 micrograms/l and 10 micrograms/g creatinine for Cd-B and Cd-U respectively. PMID- 1303959 TI - Critical levels of blood and urinary cadmium, urinary beta 2-microglobulin and retinol-binding protein for monitoring cadmium health effects. AB - The critical levels for monitoring cadmium health effects in 358 workers engaged in ore crushing/roasting (cadmium concentration in the workplace air 2.5-6.5 mg/m3), dry smelting (10.8-23.3 mg/m3), cadmium melting (0.01-0.16 mg/m3), and ingot making (2.8-4.7 mg/m3), were investigated. Exposure parameters such as blood and urinary cadmium were determined, together with biological parameters such as proteinuria, amino acids, glucose, beta 2-microglobulin, retinol-binding protein, albumin, plasma beta 2-microglobulin, creatinine clearance, tubular reabsorption of beta 2-microglobulin and phosphate, and blood and urinary levels of zinc, copper and lead. Factor analysis and stepwise regression analysis were then applied to the data to classify parameters and to find the main contributing parameter. Blood and urinary cadmium, urinary beta 2-microglobulin, retinol binding protein and the ratio of urinary beta 2-microglobulin to albumin were also subjected to multiple correlation analysis, multiple regression analysis and the Chi-square test was applied to contingency tables. It is concluded, based on the data, that cadmium health effects may be assessed by using the following critical levels: blood cadmium: 10 micrograms/l, urinary cadmium: 10 micrograms/g creatinine; urinary beta 2-microglobulin: 2000 micrograms/g creatinine, urinary retinol-binding protein: 200 micrograms/g creatinine and a ratio of urinary beta 2-microglobulin to albumin of 0.001. PMID- 1303960 TI - Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study. AB - The assessment of acceptable exposure levels to cadmium in the work or general environment frequently relies on the analysis of the relationships between urinary cadmium (an indicator of the body burden) and proteins used as markers of nephrotoxicity. A possibility which cannot be excluded a priori is that the relationships between cadmium and proteins in urine might sometimes result from renal dysfunction unrelated to cadmium toxicity. To test this hypothesis, we have measured cadmium in the urine of 114 pregnant women of whom about 20% had developed a reversible tubular proteinuria. Cadmium excretion was correlated significantly with age but not with duration of pregnancy nor with low molecular weight urinary proteins. This indicates that tubular dysfunction unrelated to cadmium exposure does not necessarily increase cadmium excretion. Hence, these data support the conclusion of the recent Cadmibel Study on the renal tubular effects of cadmium on the general population of Belgium. PMID- 1303961 TI - The World Health Organization study on health effects of exposure to cadmium: morbidity studies. AB - Studies according to the protocol of the WHO Regional Office for Europe were performed in Germany, the Netherlands and Belgium. Pilot studies were performed in Czechoslovakia, Hungary and Poland. The results of the Belgian study are described elsewhere; some striking results of the other studies are reported here. The highest levels of cadmium in blood (Cd-B) were reported in a cadmium polluted area in Hungary, the lowest in a non-polluted urban area. In Poland, levels were enhanced in polluted and non-polluted areas. The highest levels of cadmium in urine (Cd-U) were found in Hungary, the lowest in the Netherlands. In nearly all the studies significant increases in both Cd-B and Cd-U were found in cadmium-polluted areas. The picture is less clear with regard to the biological effect parameters. The renal parameters were sometimes significantly enhanced for the polluted areas, but sometimes the opposite was reported. Because of the many confounding variables, stratification at least by smoking behaviour, sex and age is necessary if firm conclusions are to be reached. A better approach, however, is to use multivariate regression analysis. This technique allowed the calculation of the relation between Cd-U and age in the German and Dutch studies, and between Cd-U and age in the German and Dutch studies, and between Cd-U and NAG, AAP, Alb-U and Creat-S levels. PMID- 1303962 TI - Health effects of cadmium with special reference to studies in Japan. AB - This paper gives an overview of the health effects of cadmium with special emphasis on the natural history of cadmium poisoning. The following questions are discussed: (1) Do the renal changes caused by cadmium result in both glomerular and tubular dysfunction? (2) What is the fate of these renal changes? (3) What is the relationship between renal changes and osteomalacia? (4) Is there a dose response relationship between cadmium exposure and renal dysfunction? (5) What is the solution to the enigma of cadmium and respiratory cancer? Although innumerable papers have been published, the above questions remain unanswered. The natural history of cadmium poisoning is ironically more complicated than that of communicable diseases in man despite the fact that the element is static and not propagated in living organisms. PMID- 1303963 TI - Is cadmium genotoxic? AB - Previous evidence that cadmium(II) causes gene mutations in bacteria or mammalian cells was weak. However, alterations in protocol have recently led to better evidence for its mutagenicity, especially in bacteria. Mutagenicity results may be confounded by tolerance mechanisms. Exposure of DNA in vitro to Cd2+ or to Cd2+ hydrogen peroxide does not result in strand breaks or alkali-labile sites. The fact that bacterial and mammalian cells appear to sustain some type of repairable DNA damage after exposure to Cd2+ suggests that the damage must be caused in an indirect manner. Recently, the ability of cadmium-metallothionein complex to cause DNA strand breaks has been described. Cd2+ also induces a "pro oxidant state" by causing a depletion of cellular glutathione. This finding is consistent with the role of Cd2+ as a clastogen and may explain its weak mutagenicity at loci which cannot detect complex mutations. Cd2+ can also inhibit DNA repair, and can therefore act synergistically with certain mutagens and, presumably, carcinogens. PMID- 1303964 TI - Chromosomal effects of cadmium exposure in humans. AB - Cytogenetic studies on subjects occupationally or environmentally exposed to cadmium are reviewed and discussed. After a first report of increased chromosome aberrations in lymphocytes of itai-itai patients from Japan, several studies on workers occupationally exposed to cadmium gave conflicting results. These differences may perhaps be explained by the action of co-factors (e.g., nutritional deficiencies in itai-itai patients; concomitant exposure to other metals in some occupational groups), or by different levels of exposure. In a study on cadmium workers with a wide range of cumulative exposure, as compared with matched controls, an increase in chromosome-type aberrations in lymphocytes, an indicator of cumulative damage, was found only because of the increased rates in the subgroup with the highest cumulative exposure and cadmium burden. As far as environmental exposure is concerned, of two recent reports, one from China is positive for chromosome aberrations and the other, from Japan, is negative for sister chromatid exchanges. PMID- 1303965 TI - Immunotoxicology of cadmium. AB - A number of investigations have suggested that cadmium may exert immunosuppressive effects in animals even though conflicting findings, due mainly to varying conditions of exposure, have been reported. Overall, cadmium has been shown to enhance humoral immune responses at low levels of exposure, whereas higher ones may result in either no effect or decreased antibody production. By contrast, cell-mediated immunity was more consistently shown to be depressed. Similarly, phagocytosis, natural killer cell activity and host resistance toward experimental infections were markedly impaired in most instances. Very few data are available regarding cadmium immunotoxicity in humans. Hypersensitivity reactions have so far not been described. No immune alterations were found to be associated with "chronic cadmium disease", whereas a depressed phagocytosis, the clinical relevance of which remains to be established, was recently documented in cadmium-exposed workers. Further investigations are therefore needed to determine how immunotoxic cadmium actually is and what health consequences are to be expected in occupationally or environmentally exposed humans. PMID- 1303966 TI - Cadmium exposure in rats and tumours of the prostate. AB - Recently, we completed three chronic studies in rats indicating that cadmium exposure can induce tumours of the prostate. In the first study, s.c. cadmium exposure increased prostatic tumour incidence only at doses below the threshold for cadmium induction of testicular dysfunction (5.0 mumol/kg). In a second study, prostatic tumours were elevated at higher doses of cadmium (30 mumol/kg, s.c.) if testicular dysfunction was prevented by zinc treatment. Finally, dietary cadmium (25-200 micrograms/g) increased prostatic neoplastic lesions. Thus it appears that cadmium produces prostatic tumours only if testicular function is maintained. Accumulation and retention of prostatic cadmium appears to be highly androgen-dependent. Furthermore, metallothionein, a protein associated with tolerance to cadmium, may be deficient in the rat prostate, and the prostatic metallothionein gene, at least in the ventral lobe, may be unresponsive to metal stimuli. The finding of prostatic cancer in cadmium-treated rats clearly supports a possible role for exposure to cadmium in human prostatic cancer. PMID- 1303967 TI - Induction of tumours of the haematopoietic system by cadmium in rats. AB - Several of our recent studies in rats indicate an association between exposure to cadmium and haematopoietic tumours. In the first study, male WF rats received dietary cadmium (0-200 micrograms/g cadmium as cadmium chloride) for up to 77 weeks. A dose-related increase in large granular lymphocyte (LGL) leukaemia was observed with a maximal incidence in rats fed 100 micrograms/g cadmium. In a second study, male F344 rats received a single high dose of cadmium chloride (30 mumol/kg, s.c.) and were observed for 90 weeks. The high natural incidence of leukaemia in these rats (24%) was markedly reduced (6%) by this dose of cadmium. The paradoxical effects of cadmium on haematopoietic tumours may be the result of a dose-related spectrum of lymphotoxicity ranging from cell-specific cytotoxicity and carcinogenicity to destruction of key progenitor cell populations. PMID- 1303968 TI - Pulmonary carcinogenicity of cadmium by inhalation in animals. AB - Although, the tumorigenic effect of cadmium after subcutaneous and intramuscular injection has been known since 1961, lung tumours after inhalation exposure were reported only more than 20 years later by Takenaka et al. (1983), using cadmium chloride aerosols. Based on these results, aerosols of cadmium sulfate, cadmium oxide and cadmium sulfide pigment were investigated for carcinogenic effects after inhalation exposure in rats, hamsters and mice. All the cadmium compounds tested appeared to have a very similar carcinogenic potency in the rat lung, whereas no exposure-related tumours occurred in hamsters and in mice only cadmium oxide seemed to increase the lung tumour rate. Subsequent analytical investigations of the aqueous suspension of cadmium sulfide used to generate the aerosol showed that it was soluble in water to some extent as a result of photo oxidation. The exposure atmosphere therefore actually consisted of a mixture of sulfide and sulfate, and the observed lung tumour rate must be attributed to a combined action of the two compounds. For this reason, a clear-cut carcinogenic effect of cadmium sulfide could not be proved by this inhalation study, but because of the high carcinogenic potency of cadmium ions in the rat lung and because cadmium sulfide retained in the lung is bioavailable to a certain extent, aerosols of this compound should be regarded as a probable human carcinogen. PMID- 1303969 TI - Validity and limitations of animal experiments in assessing lung carcinogenicity of cadmium. AB - Several cadmium compounds have been observed to induce in rats, but in rats only, a dose-dependent increase in lung cancer. A similar sensitivity to lung cancer induction in both humans and rats can be deduced from a comparison of the histogenesis of tumours and the dose response to radiation, since similar numbers of DNA lesions are produced. Since the carcinogenic action of cadmium is limited to the site of deposition, the toxicokinetics of inhaled particles in human and rodents are discussed in relation to the exposure of the respective target cells in both species. It is stressed that the rat may be much more sensitive to the induction of cancer following the retention of poorly soluble compounds. A comparison of the possible dose-effect response in humans and the dose response in rats showed that the shape of the "dose" response cannot be extrapolated. Finally, clonogenicity and DNA repair of tracheal cells sublethally exposed in vitro to cadmium differ significantly in rats and hamsters. This may explain why hamsters exposed in vivo do not develop tumours. PMID- 1303970 TI - Methodological aspects of the epidemiological association between cadmium and cancer in humans. AB - The main epidemiological evidence of an association between cadmium exposure and human cancer comes from studies on occupational groups such as smelter and nickel cadmium battery workers. Lung and prostate are the sites more frequently reported to be at increased risk of cancer, but the various epidemiological studies do not enable any definite conclusion to be reached. Methodological problems in the interpretation of these studies include: (i) the assessment of exposure to cadmium; (ii) the dose-response relationship between indicators of cadmium exposure and cancer risk; (iii) concomitant exposure to occupational carcinogens, mainly nickel and arsenic; (iv) confounding by non-occupational risk factors, such as smoking and diet; and (v) interaction between cadmium and other exposures. The confounding effect of smoking and diet is particularly interesting since they may act both as additional uncontrolled sources of cadmium and as independent cancer risk factors. PMID- 1303971 TI - Is cadmium a human carcinogen? AB - Continuing observations on cadmium-exposed workers have failed to yield evidence of an increased mortality from prostatic cancer, as initially suspected. There is, however, evidence of an increased mortality from lung cancer and, in at least two of the studies, of a dose-response relationship, but interpretation of these studies with regard to the role of cadmium is complicated by concurrent exposure to other known or suspected carcinogens, including arsenic, nickel, beryllium, chromium and heated mineral oils. An update of a long-term cohort mortality study from 17 plants in England employing a wide range of cadmium processes, while confirming an increased lung cancer risk related to intensity of cadmium exposure, shows some evidence of this risk also being associated with exposure to arsenic. It is thus not possible at present to attribute the excess mortality from lung cancer to cadmium owing to the presence of multiple confounding factors in the populations studied. Their role in the 17-plant study is currently being further investigated. PMID- 1303972 TI - A quantitative assessment of lung cancer risk and occupational cadmium exposure. AB - We have performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium exposed workers. The findings were analysed using a life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms of Poisson and Cox proportionate hazards models to examine dose-response relationships. An excess mortality from lung cancer was observed for the entire cohort (SMR = 149,95% CI = 95-222). Lung cancer mortality was significantly elevated among non-hispanic workers, among those in the highest cadmium-exposure group, and among workers with 20 or more years since first exposure. A statistically significant dose-response relationship was evident in nearly all of the regression analyses. Based on our analyses, the lifetime excess lung cancer risk at the current OSHA standard for cadmium fumes of 100 micrograms/m3 is approximately 50-111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years. PMID- 1303973 TI - Biological monitoring in the occupational setting--relationship to cadmium exposure. AB - Statutory health surveillance of occupational exposure to cadmium exists in most Western countries. For biological monitoring, both indicators of internal dose and indicators of effect are available. Cadmium in urine is an indicator of chronic exposure and essentially reflects the body burden under low-exposure conditions and in the absence of renal damage. Whole blood cadmium is primarily a useful indicator for use in evaluations of recent exposures. Biological threshold limit values for cadmium in urine and blood are based on the correlation of biological levels with thresholds for renal dysfunction. The use of markers of high and low molecular weight proteinuria should be integrated into the health surveillance of cadmium-exposed workers. Priority should be given to the determination of albumin and of proteins such as beta 2-microglobulin, retinol binding protein and alpha 1-microglobulin. Interpretation of biological monitoring data in terms of the threshold values requires a programme of periodic biological, medical and environmental monitoring. PMID- 1303974 TI - Biological monitoring of the general population for cadmium. AB - Over 2000 blood samples and about 1000 24-h total food duplicates were collected in 49 non-polluted regions in Japan, and analysed for cadmium (Cd-B and Cd-F). Cd B increased with age to reach a plateau at 40-59 years, where the geometric mean (GM) Cd-B was 3.2 ng/ml in men and 3.7 ng/ml in women. Smoking also increased Cd B. The GMs of Cd-F were 43.9 and 37.0 micrograms/day for men and women, respectively, with boiled rice as a major source of cadmium (> 40%). Cd-B correlated significantly with Cd-F when compared on a regional mean basis. Similar Cd-B analyses among non-smoking women showed that Cd-B was lower in Korea (ca. 1.6 ng/ml) and in China (1.3 ng/ml) than in Japan. This observation is in accordance with the fact that rice in Korea (16.1 ng/g dry weight) and China (7.6 ng/g) contained less cadmium than that in Japan (52.5 ng/g). A preliminary follow up in 1989 suggests a decrease in Cd-B (by ca. 30%) among the Japanese population, probably due to a reduction in cadmium in rice (ca. 14%) and a decreased rice intake. PMID- 1303975 TI - Quantitative analyses of cadmium: quality assured? AB - Legislation has been a powerful stimulus for measuring the concentrations of cadmium in many different matrices. Unfortunately, much of the quantitative data in the literature is flawed because of a paucity of information on the reliability of sampling and measurement. Non-specific analytical methods, inaccurate calibration, lack of matrix reference materials, poor laboratory technique in general, lack of statistical control, and ignorance of contamination all militate against gathering truly valid data. The implications for bioavailability of chemical and physical speciation also need to be considered, especially in the analysis of airborne particulates and foodstuffs. Effective quality assurance serves several distinct purposes: (1) to allay analysts' concern for the quality of their work; (2) to discharge management's responsibility for the cost and quality of the laboratory's output; (3) to inform users of the quality of the data sets; and (4) to provide archival data and documentation. PMID- 1303976 TI - Analytical quality control of cadmium and lead in blood and cadmium in urine: results of its implementation during a five-year epidemiological study. AB - Quality-control programmes are very important in assessing the reliability of biological analyses. Such programmes are essential if misleading results in epidemiological studies dealing with low levels of exposure to heavy metals present in the general environment (e.g., cadmium, lead) are to be avoided. Internal and external quality-control programmes for the measurement of cadmium and lead in blood and of cadmium in urine were implemented from 1985 to 1989 in support of a national epidemiological study, Cadmibel (2327 participants), conducted in Belgium to assess the effects of environmental exposure to cadmium and lead on the general population. Apart from these programmes, inter comparisons between the two participating laboratories were carried out on 10% of the samples. The results of these quality-control programmes met external acceptability criteria, emphasizing the analytical proficiency of these measurements at the relatively low concentrations in the Cadmibel study. PMID- 1303978 TI - Global scenario of disaster--problems & challenges. PMID- 1303979 TI - Preparedness status in disaster management study in West Bengal. PMID- 1303977 TI - Definition of reference values for Cd-B and Cd-U: methodological aspects and preliminary results. AB - In the present study, a definition of the reference values of blood cadmium (Cd B) and urinary cadmium (Cd-U) was attempted, adopting the same methodology as that used for Hg-B by ICOH and IUPAC. Papers published from 1976 onwards were reviewed. The majority of the studies were concerned with the formation of control groups for toxicological and epidemiological investigations rather than with the definition of reference values. Since the number of subjects for whom data on cadmium were available was small, only the data on Cd-B were considered. After evaluation, only four studies were found to be suitable for the establishment of tentative reference values for Cd-B. It is essential in all such studies to check the statistical and analytical methods for correctness, and the case-list must be selected taking smoking into account as the main interfering factor. It was found that Cd-B values show less dispersion when geometric means and standard geometric deviations are used instead of arithmetic means and standard deviations. PMID- 1303980 TI - Nutritional measures for the management of nutritional disaster. PMID- 1303981 TI - Perspective for natural disaster reduction in India. PMID- 1303982 TI - Preparedness programme for natural and man-made disasters. PMID- 1303983 TI - MCH record maintenance at primary health centre level. AB - Scrutiny of MCH records of 1977-78 and 1988 at PHC level revealed glaring deficiencies in their maintenance e.g. missing of entries., duplicate entries etc. Extent of supervision of service records was extremely low. Record linkages could be poorly established and thus present mechanism of health care delivery could not ensure continuity of care. The level of record maintenance has almost remained same over a decade period. This can be avoided by modifying the information system, making records at the PHC level simple, action oriented with built in system of evaluation and involving community in its maintenance and utilisation. PMID- 1303984 TI - An enquiry into work environmental status and health of workers involved in production of incense sticks in city of Bangalore. AB - This preliminary study represents 10% of the workers in this occupation in Bangalore. The industry is highly commercial in nature and the city of Bangalore; has the largest number of units in Karnataka State. The study provides base line data relating to some morbidity conditions for future comparisons. Low back ache, tiredness, head ache, irritation in the eyes, sleeplessness, joint pains, chest pain, postural giddiness, persistent running nose, abdominal pain, cough and tremors of hands, were some of the common conditions elicited among the workers. Some of the conditions were identified to be possibly related to various processes within the industry. Particularly low back ache and irritation in the eyes (rolling and dipping), tremors of hands (packing). It is very likely that in the final stages when certain chemical ingredients are added which finally give the scent, the chances of pollutants entering either through skin or inhalation is possible. Environmental monitoring has not shown any appreciable dust hazard. The study has helped in identifying some of the areas in the work environment which required improvement. There is a need for social workers, medical personnel and industrial hygienists to explore the possibilities of minimizing possible hazards. A national sampling survey in other parts of the country might also be beneficial. PMID- 1303985 TI - Respiratory illness and tuberculin sensitivity among children below 15 years of age in a rural community. AB - The incidence of respiratory illness and tuberculin sensitivity of children below 15 years were studied among 245 families in village Chinimore and the observations were compared between two groups families keeping livestock and families non-keeping livestock. There were 135 (out of 446) children with respiratory illness with 30.2% incidence and 45 (out of 187 tuberculin tested) children were positive to Mantoux test. Families keeping livestock had statistically significantly more (P 25.18 of 0.1% level) tuberculin sensitive children. PMID- 1303986 TI - Attitude of Indian urban adults towards mental illnesses. AB - In an urban area of Jhansi 238 adults were interviewed to asses their views regarding mental illnesses. Mental illness was not perceived as a serious disease. Cancer was perceived as the most serious disease. Worries, faulty upbringing, overwork were perceived as a cause of mental illness by majority. Early identification sings of mental illness described by them were difficulty in sleeping, changes in facial expression and feeling of impending mental imbalance. Marital alliance with them was not favoured. However, a sympathetic attitude towards mental patients was favoured. Avoiding tension, adapting oneself to circumstances, a consulting elders were considered as preventive measures against mental illness by majority. PMID- 1303988 TI - Child to child communication: a gainful experience. PMID- 1303987 TI - Profile of oral contraceptive usage by females of the northern part of West Bengal. PMID- 1303990 TI - A socio economic survey of self styled leprosy colony at Aska. PMID- 1303989 TI - Distribution and trends of HIV infection in blood donors of four metropolitan cities. AB - Screening for HIV infection has been made mandatory for every unit of blood collected for transfusion in major cities of the country, having facilities for such screening. Results of HIV screening among blood donors received from the 4 Metropolitan cities of Delhi, Bombay, Calcutta and Madras have been analysed year wise from 1989 to 1991 to determine the magnitude and trends of HIV infection in different categories of blood donors and the seropositivity rates seems to be increasing over time. Universal coverage of HIV screening for donated blood has not been fully achieved and the justification and urgency for achieving complete coverage is highlighted. PMID- 1303991 TI - Awareness about sore-throat, rheumatic fever and rheumatic heart disease in a rural community. AB - This I.C.M.R. study was conducted in 74 villages of Chiraigaon block, Varanasi, U.P., during the period March 1983 and December 1986. Before and after health education awareness survey about sore throat, rheumatic fever and rheumatic heart disease was carried out by interviewing 315 persons by stratified random sampling. The study shows that there is significant increase in the knowledge about most of the symptoms, causes, consequences and preventive measures of sore throat, rheumatic fever and rheumatic heart disease. This paper highlights the importance of health education as a vital component of rheumatic heart disease control programme. PMID- 1303992 TI - Family welfare programme in India--the child survival context. PMID- 1303993 TI - Salmonella in foods of animal origin: enterotoxigenicity and antibiogram. AB - A total of 82 strains of Salmonella belonging to 17 different serotypes recovered from foods of animal origin were in this study. Out of 39 cell free culture supernatants (CFCS), tested for enterotoxigenicity, 26 (66.67%) were positive in rabbit ileal loops. None were found positive for enterotoxigenicity in infant mouse model. According to the disc diffusion methods of testing, gentamycin, nalidixic acid and chloramphenicol were found to be most effective against Salmonella organism. Erythromycin and oxytetracycline were least effective. PMID- 1303994 TI - Study of leprosy among slum dwellers in Pune. Part-I. Prevalence. AB - While conducting a point prevalence total population survey in Ghorpuri slum in Pune, the overall prevalence or leprosy was 9.16 per thousand. The prevalence rate varied in different bastis with Madari basti having a very high prevalence rate of 17.31 per thousand and showing clustering. Prevalence was highest in age group 31-40 years, females, Muslims, Widower/widow, skilled workers, illiterates and primary school educated and the lower socio-economic groups. Joint families had the highest prevalence of leprosy (20.83/1,000) and also higher prevalence was seen in families with more than 7 members. PMID- 1303995 TI - Study of leprosy among slum dwellers in Pune. Part II--Disabilities. AB - While conducting a leprosy survey in an urban slum in Pune 45 cases of leprosy were detected in a population of 4915 and only 7 of these cases had some disability. Disability rate in the leprosy cases was 15.56 percent, and maximum number had Grade 2 disability of hands or feet. Disability was higher in the higher age groups, males, Hindus, widower/widows, unemployed and lower socio economic classes. Majority of the cases had a very low Disability Index DI (2) between 0.10 to 0.69 which is heartening and proves the successful implementation of the National Leprosy Eradication Programme. PMID- 1303996 TI - Social aspects of recurrent abdominal pain (RAP) in children. PMID- 1303998 TI - Presidential address. Public health. PMID- 1303997 TI - Disaster epidemiology and health management. PMID- 1303999 TI - Perspectives in health planning under minimum needs programme. PMID- 1304000 TI - Responsibility of health professionals: preparing ourselves for the coming twenty first century. PMID- 1304002 TI - Child survival and safe motherhood. PMID- 1304001 TI - Prevalence of diarrhoeal diseases amongst tribals of Car Nicobar Island, India. AB - In a cross sectional study of total 14514 tribal Nicobarese people of Car Nicobar Island, an union territory of India, situated in Bay of Bengal, morbidity, mortality and treatment practices of diarrhoeal diseases of under-five children were surveyed. The incidence of diarrhoea (0.2 episode/ch.year), Crude death rate (3.6/1000) and IMR (31/1000 live births) were exceedingly low as compared to SouthEast Asian Countries including mainland of India. ORS utilisation rate was high (41%) as compared to the National figure (12.0%). This is the first study of it's kind carried out in this island and amongst the Nicobarese tribe in India. A preliminary study carried out among the mothers of the hospitalised children indicated that protective behaviours like breast feeding, hand washing, use of chlorinated water and proper disposal of stool were regularly being practiced by the community traditionally. An in-depth study on risk factors of diarrhoea in this island can yield useful clue for describing the same. PMID- 1304003 TI - Relations among verbal and nonverbal cognitive skills in normal language and specifically language-impaired children. AB - This study tested the hypothesis that specifically language-impaired (SLI) children have a qualitatively different cognitive system from that of normal language (NL) children. Twenty NL and 20 SLI children between the ages of 4:2 (years:months) and 5:11 were presented with experimental language-learning measures, experimental nonverbal measures, and verbal and nonverbal norm referenced tests. A confirmatory analysis of the covariance matrix structures of the two subject groups indicated that relations among cognitive skills differed between NL and SLI children. In addition, a planned comparison indicated that the relation between nonverbal rule-induction and novel bound-morpheme learning differed significantly between groups. The findings indicate that a "qualitative differences" model of specific language impairment better accounts for the co occurrence of poor verbal and poor nonverbal cognitive skills in SLI children than a "low-normal" model. PMID- 1304004 TI - Use of the Clark-Madison Test of Oral Language with the hearing-impaired: a content validity and comparative study. AB - This study examined the content validity of the Clark-Madison Test of Oral Language (CMTOL) as a measure of nonwritten expressive language with hearing impaired children. Twenty severely hearing-impaired children were administered the CMTOL using total communication. All test administrations were considered valid. The content of the test was generally found to be valid. The content validity of selected items is discussed. A comparison of the performance of the hearing-impaired to a group of normal-hearing respondents revealed a different profile of strengths and weaknesses than did intragroup analysis. PMID- 1304005 TI - Voice therapy practices and techniques: a survey of voice clinicians. AB - Members of the American Speech-Language-Hearing Association Special Interest Division on Voice were asked to rate statements which emanated from a previously conducted national survey regarding the practice of voice therapy (Larson and Mueller, 1991). Respondents rated eight data-based statements on a five-point scale as to agreement/disagreement. Results indicated strong agreement with previous findings with the exception of the item addressing treatment time. Implications of these results are discussed. PMID- 1304006 TI - Cerebral amino acids and energy metabolites in the growth retarded rat fetus under normoxia and hypoxia. AB - The effect of intrauterine growth retardation (IUGR) on striatal energy metabolites and amino acid concentrations was studied in the fetuses of eight nulliparous rat dams after uterine artery ligation on day 18 of gestation. On day 22 (term = 23), four dams were subjected to normoxia and four to hypoxia (10% oxygen) for 58 min, while monitoring hemodynamics and blood gases. After decapitation of the dam, fetuses were delivered by sectio and decapitated. The measured parameters in the dams were stable under normoxia but exhibited decreased oxygen availability under hypoxia. Striatal energy balance was preserved in IUGRs, both under maternal normoxic and hypoxic conditions, compared to appropriately grown (AGA) littermates. Under maternal normoxia, the striatal concentration of aspartate was reduced (P < 0.01) in IUGRs and the level of alanine was increased (P < 0.01) as compared to AGAs. Under hypoxia, the level of GABA was higher in IUGRs (P < 0.01). Lactate was increased in all fetuses under hypoxia. It is concluded that striatal energy metabolism is preserved in IUGR rat fetuses in late gestation under both maternal normoxia and hypoxia. Amino acid metabolism, however, is disturbed and depends on the degree of growth retardation and on the severity of perinatal stress. PMID- 1304007 TI - Effects of alveolar hypoxia on the pulmonary circulation and lung mechanics after cromolyn sodium and U-60,257 in lambs. AB - Because alveolar hypoxia (HYP) triggers pulmonary mast cell degranulation with elaboration of vasoactive mediators such as leukotrienes, we investigated the effects of aerosolized cromolyn sodium (CS), a mast cell stabilizing agent, and U 60,257(U) (a leukotriene blocker) on the circulation, lung mechanics and thromboxane (TXB2) levels in 11 lambs during acute exposure to HYP. Studies were performed in awake, chronically instrumented animals, once after placebo (saline) and again after CS (100 mg; n = 5) or U (90 mg; n = 6). Pulmonary arterial pressure increased 42% during HYP after saline, and 32% and 19% after CS and U, respectively. Pulmonary vascular resistance did not change during HYP after CS or U. Systemic arterial pressure was unchanged after saline and CS but decreased after U; systemic vascular resistance dropped after both CS and U. No changes were seen in tidal volume, lung compliance or airway resistance during HYP after saline or either drug, but minute ventilation increased during HYP in all studies. TXB2 increased during HYP after saline in both studies and was not altered by CS. In contrast, after U, TXB2 decreased. Thus, U more effectively blunted the pulmonary vascular response to HYP than CS and resulted in mild systemic hypotension. The drop in TXB2 after U suggests leukotriene-induced thromboxane synthesis contributes to regulation of pulmonary, and possibly, systemic vasoactivity. PMID- 1304008 TI - Corticotropin releasing hormone concentrations in umbilical cord blood of preterm fetuses. AB - Corticotrophin releasing hormone (CRH), dehydroepiandrosterone sulfate (DHEAS) and cortisol were measured in umbilical cord plasma obtained from 90 preterm and 98 term fetuses. Maternal plasma was obtained from 23 women who delivered preterm and from 23 women matched for gestational age who ultimately delivered term infants. Mean umbilical cord plasma CRH concentration was significantly higher in the preterm fetuses (n = 69, 538 +/- 63 pg/ml) compared to the term fetuses (n = 98, 280 +/- 22 pg/ml, P < 0.01). Mean DHEAS level in the preterm fetuses was 208 +/- 22 mg/dl (n = 56), cortisol level was 7 +/- 1 mg/dl (n = 58). Umbilical plasma CRH concentrations (808 +/- 170 pg/ml) were significantly higher at 24-27 weeks than at 28-31 or 31-34 weeks gestation. Cortisol levels (12 +/- 3 micrograms/dl) were highest at 24-27 weeks. Mode of delivery and the presence of labor did not affect fetal CRH levels. The highest fetal CRH levels were measured in the pregnancies complicated by hypertension as well as prematurity; however, fetal CRH levels remained higher in the preterm group compared to the term group when hypertensive pregnancies were excluded. Maternal plasma CRH levels were significantly higher in the group that delivered preterm compared to women who delivered at term matched for gestational age (1058 +/- 184 pg/ml compared to 456 +/- 71 pg/ml, P < 0.00).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304010 TI - The effects of gestational age and labour on the breathing and behaviour response to oxygen and umbilical cord occlusion in the fetal sheep. AB - We tested the hypothesis that the continuous breathing response to oxygen or oxygen plus umbilical cord occlusion, in the fetal sheep, could be modified by gestational age or labour. We studied 35 chronically instrumented fetal sheep on 84 occasions during late gestation (124 to 141 days), using our window model (Rigatto, 1984). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of about 30 cm H2O. Inspired nitrogen, and 100% O2 were given to the fetus during one cycle each. While on 100% O2 the umbilical cord was occluded using a balloon cuff. We found that: (1) the continuous breathing response to 100% O2 occurring in 8% of the experiments at a gestational age less than 130 days, in 25% from 130 to 134 days and in 45% at gestational ages greater than 134 days (P < 0.01); (2) at similar gestational age intervals the breathing responses to umbilical cord occlusion were 67%, 84%, and 100% (P < 0.01); and (3) in the presence of labour, 45% of the experiments responded to O2 with continuous breathing as compared to 23% in the absence of labour (P < 0.01). Cord occlusion did not affect these values. Because the highest PaO2 achieved increased significantly to 128 days but not thereafter it is unlikely that these results can be explained on the basis of an increase in PaO2 alone. We speculate that there is an age related maturation of the inhibition of breathing normally present in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304009 TI - Maternal fever at parturition and its effects on the newborn rabbit. AB - The febrile response to administration of endotoxin has been reported to be suppressed in both pregnant animals at term and in their newborn. In a previous study we found that newborn rabbits under appropriate conditions to develop a febrile reaction to injected endotoxin. In this investigation we sought to discover whether pregnant rabbits at term had a febrile response to endotoxin, and if so, its effect on thermoregulation in their newborn. Endotoxin (E. Coli LPS) was injected into 19 pregnant rabbits at term. Six delivered spontaneously within an hour. At one hour, 13 were given oxytocin, and a further 8 delivered within five minutes. The colonic temperature (Tc) of the mothers before endotoxin administration and at delivery, and of their young, was measured. The results were compared with those of 10 pregnant rabbits not given endotoxin, and their young. Within 15 min of delivery newborn rabbits from each litter were placed on a thermal gradient to assess their thermoregulatory responses. Pregnant rabbits at term developed an impressive febrile response to injected endotoxin and their young were born with high colonic temperatures. Newborn rabbits from febrile mothers selected higher thermal environments and maintained a higher colonic temperature than the newborn of non-febrile mothers. We conclude that fever is sustained in the first hours of life in the newborn of mothers injected with endotoxin. The possible mechanisms are of considerable interest. None of the pregnant rabbits died after endotoxin administration, but the stillbirth rate was 50% compared with 10% in non-febrile does. PMID- 1304011 TI - Thirsting for the fountain of youth: myth and reality. PMID- 1304012 TI - Breast-feeding is best for every baby: what else in news? PMID- 1304013 TI - Influence of admission weight on neonatal mortality amongst hospitalised neonates in Calcutta. AB - The study was conducted on 785 neonates aged up to 28 days to evaluate the influence of admission weight on mortality. It was observed that there were 200 (25.5%) cases of septicaemia, 134(17.1%) of diarrhoea, 120(15.3%) each of prematurity related conditions and neonatal jaundice, 117(14.9%) of respiratory diseases and 94 (11.9%) cases of convulsion. There were total 182(23.18%) deaths comprising 70(38.5%) from prematurity related conditions, 40(22%) from diarrhoea, 35(19.2%) from respiratory diseases, 26(14.3%) from septicaemia, 8(4.4%) from neonatal jaundice and 3(1.6%) deaths from convulsion. The incidence of deaths among neonates weighing less than 2500 g on admission was 59.2% in diarrhoeal diseases, 53.4% in respiratory diseases and 44.6% in other conditions compared to those of 10%, 8.2% and 7.1% respectively in neonates having admission weight more than 2500 g. The findings are statistically significant. The results of the study indicate that low admission weight should be considered as a predictor of mortality among neonates. PMID- 1304014 TI - Epidemiological study of the victims of vehicular accidents in Delhi. AB - The mortality and morbidity connected with road traffic accidents are increasing at an alarming rate throughout the world as a direct result of the rapid industrialization and increase of fast moving vehicles combined with lack of traffic sense of road users of this country. Epidemiological aspects manifested in vehicular accidents in New Delhi during the year 1983-84 are illustrated here. PMID- 1304015 TI - A suspected case of dapsone poisoning. PMID- 1304016 TI - Will bedtime dose of atenolol be more effective in secondary prevention of coronary artery disease? PMID- 1304017 TI - Psychotherapy in general practice. PMID- 1304018 TI - Results of delayed operations for ruptured supratentorial aneurysms in 22 consecutive patients. AB - Twenty-two patients with surgically treated ruptured aneurysms were reviewed retrospectively regarding age, sex, aneurysm site distribution, clinical grading, rebleeding, timing of surgery and long term results. The most common aneurysm site was in the Anterior Communicating artery (44%). The mean time between aneurysmal subarachnoid hemorrhage and surgery was 20 days. There were 4 cases with intraoperative rupture. The outcome was favorable in 63.6 per cent after a mean follow-up of 21 months. The overall mortality rate was 22.7 per cent. The results may be improved by an early, well planned operation. PMID- 1304019 TI - Osseous adenocarcinoma of unknown primary site: study of survival and prognostic factors. AB - A prospective study of 149 patients suffering from adenocarcinoma of unknown primary site (ACUPS) of bone was carried out. The tumors are classified as 63 extraspinal, 67 spinal and 19 mixed involvement. Upon meticulous physical examination, Virchow's node was detected in 15 cases, rectal shelf in 11 cases and hepatomegaly in 44 cases. Blood chemistry showed elevation of alkaline phosphatase (> 3 sigma units) in 98 cases and chest roentgenogram showed pulmonary lesions in 23 cases. Treatment was surgery and radiotherapy in 64 and two cases respectively. In all of these patients histological findings of the biopsy or resection specimen had confirmed the diagnosis of adenocarcinoma. Among 124 evaluable patients, overall survival was analysed using Kaplan-Meier life table analysis. Survival rates at one, two and four months after diagnosis were 80.7, 60.5 and 25 per cent with a mean and median survival times of 90 and 77 days respectively. Statistical analysis was also performed to ascertain the prognostic importance of the following variables: age, gender, Virchow's node, rectal shelf, hepatomegaly, serum alkaline phosphatase, pulmonary lesion, and multiplicity and site of the osseous lesions. The presence of pulmonary lesion or hepatomegaly significantly produced unfavorable impact on the duration of survival (p = 0.0004 and 0.0150, respectively) while other remaining factors had not. PMID- 1304020 TI - Agranulocytosis and aplastic anemia among Ramathibodi Hospital patients. AB - A one-year prospective prevalence study on aplastic anemia and agranulocytosis was performed in Ramathibodi Medical School. A total of 91,581 complete blood counts were screened for potential cases of aplastic anemia and agranulocytosis according to defined criteria. Nineteen cases of aplastic anemia and five cases of agranulocytosis were found. The prevalence of the two conditions was discussed. PMID- 1304021 TI - Comparative efficacy of spiramycin and erythromycin in acute exudative tonsillitis in adults: a randomized controlled trial. AB - A randomized control trial was designed to compare the efficacies of spiramycin given one gram twice daily and erythromycin given 500 mg thrice or four times daily in the treatment of acute exudative tonsillitis in adults whose ages were over 13 years old from January 1989 to January 1991 at a community clinic. A total of 120 cases were enrolled in the study. Fifty-three patients received spiramycin while 67 received erythromycin. Group A beta-hemolytic streptococci (GABHS), S. aureus, and positive titer of Mycoplasma pneumoniae were detected in 19, 47 and 8 per cent in spiramycin group and 21, 36 and 11 per cent in erythromycin group respectively. GABHS were totally eradicated on day 3 of treatment in both groups through eradication of S. aureus was slightly slower initially in the spiramycin group. Marked improvement was similarly achieved in both groups after 3 days of therapy. Dyspepsia was felt in 34.4 and 8.2 per cent of erythromycin and spiramycin groups respectively but was tolerable by most patients. We concluded that spiramycin given twice daily was as effectively as conventional erythromycin but spiramycin is more convenient to administer and causes much less gastro-intestinal side-effect. PMID- 1304022 TI - Endoscopic removal of stone in patients with retained common bile duct stone and T-tube after cholecystectomy. Is it justified? AB - Fifteen patients with retained common bile duct (CBD) stones and T-tube and twenty patients with CBD stones without T-tube had stones removed by endoscopic method. The result of endoscopic sphincterotomy, stone extraction, stone clearance and complication in patients with T-tube was similar to the results in patients without T-tube. The presence of T-tube did not create much difficulty in stone removal and the successful rate of 86.6 per cent (13/15) was satisfactory. Endoscopic removal of retained stones in patients with T-tube is recommended when retrieval via T-tube is not available since the later has fewer reported complications with very low mortality compared to the endoscopic technique. PMID- 1304024 TI - Inflammatory aortic aneurysm: a case report and review of literatures. AB - A case of an uncommon variant of aortic aneurysm, inflammatory type, is reported. A 51-year-old Thai male presented with a pulsatile abdominal mass associated with pain. Ultrasonography demonstrated infrarenal abdominal aortic aneurysm preoperatively and operative findings revealed dense fibrous tissue around the lesion. Serological tests for syphilis and bacteriological studies of aneurysm contents were all negative. Aneurysmorrhaphy was done, using Dacron straight graft, and two serious complications developed at six and two months interval: aortocolonic and aortoduodenal fistulae. However, the patient survived the three operations. Definite diagnosis of inflammatory aortic aneurysm was confirmed by typical pathological findings. Clinical presentations, operative and pathological findings were compared to previous literature. PMID- 1304023 TI - Abnormal glucose tolerance and blood pressure in Khon Kaen. AB - To quantify the association of abnormal glucose tolerance with hypertension, a population based study was carried out in subjects aged 30-65 years with oral glucose tolerance and blood pressure measurement compared with clinic based known diabetics. In males, subjects with diabetes (newly diagnosed and clinic based) had increased systolic and diastolic blood pressure with clinical significance compared to normal. The diastolic blood pressure in diabetic males was higher than normal but was not different from IGT. In females, the differences were observed between normal vs IGT, and diabetes. The differences were independent of age and obesity. The prevalence of hypertension also increased in diabetic patients, especially for systolic hypertension. PMID- 1304025 TI - George Eric Lamming: an appreciation. PMID- 1304026 TI - Nutritional and lactational regulation of fertility in sows. AB - Two major conclusions were drawn from early studies on lactating sows. First, gonadotrophin secretion is suppressed during lactation and this constitutes the primary block to ovarian function and lactational oestrus. Second, in addition to the suckling stimulus per se, nutrition and changes in body condition during lactation have critical effects on post-weaning fertility of sows. Considerable progress has been made in defining the mechanisms that mediate the inhibitory effects of lactation on ovarian development. In sows, active secretion of luteinizing hormone (LH) constitutes an important luteotrophic signal throughout pregnancy. LH secretion may therefore increase in the immediate postpartum period in the suckled sow. In the absence of suckling, this high rate of LH secretion can result in the development of highly oestrogenic but often cystic follicles in the immediate postpartum period. Together with data from studies involving treatment with exogenous gonadotrophins or luteinizing-hormone-releasing hormone (LHRH), this indicates that ovarian sensitivity is not compromised during lactation in sows. The inhibitory effects of suckling on LH secretion, typical of established lactation, are imposed during the first 72 h post partum and from this time the inhibitory mechanism is at least partly opioid dependent. In two recently completed studies, however, it has not been possible to block the development of the suckling-induced suppression of LH by treatment with the opiate antagonist, naloxone, suggesting that other inhibitory mechanisms are involved. Differential regulation of LH and follicle-stimulating hormone (FSH) secretion is evident during lactation, probably as a consequence of ovarian inhibitory, inhibin-mediated control of FSH but not of LH secretion. There is still very little direct evidence for the mechanisms by which the metabolic state of lactating sows affect fertility after weaning. Low plasma insulin, glucose and insulin-like growth factor 1 (IGF-1), and high growth hormone (GH) and cortisol concentrations in sows in a catabolic state are all potentially involved. In lactating sows with a reasonable energy balance, the inhibitory neural effects of suckling are probably more potent inhibitors of LH secretion than are the metabolic demands of milk production. PMID- 1304027 TI - Manipulation of reproduction in sheep. AB - Active immunization of cyclic ewes against androstenedione (using melatonin, Fecundin) has been shown to increase reproductive output by about 30 extra lambs per 100 ewes put to the ram in UK sheep flocks. However, this technique has not been widely adopted within the industry. One possible reason for this is that it results in an unacceptable incidence of triplet births, even though the litter size distribution is similar to that obtained for untreated flocks with the same overall mean lambing percentage. The use of progestagen sponges plus pregnant mares' serum gonadotrophin (PMSG) for the induction of out-of-season breeding in ewes is associated with a number of recognized shortcomings. A possible reason for the variability in conception rates is the high incidence of complete embryo loss or fertilization failure in ewes that are induced to superovulate after treatment with the doses of PMSG required to promote a high oestrous response. Recent studies have indicated that slow release implants of melatonin (Regulin) can advance the onset of the breeding season of commercial sheep flocks, but only by about 4 weeks. This means that the optimum treatment window varies according to the natural breeding season characteristics for the breed. Nevertheless, this treatment appears to overcome a number of the shortcomings of progestagen sponges plus PMSG. It also produces a modest increase in litter size per ewe pregnant (about 15 extra lambs per 100 ewes) without the wide variation in birth types and birth weights associated with PMSG. The development of a laparoscopic procedure that improves conception rates after intrauterine insemination of frozen semen allows comparisons of genetic merit across flocks. This should promote far greater rates of genetic improvement for traits of high economic importance than those achieved by within-flock selection and in the last two years has allowed the development of sire-referencing schemes within the major terminal sire breeds. Laparoscopic procedures for the collection and transfer of embryos in sheep now have the potential to overcome many of the limitations of more invasive surgical approaches, although the unpredictability of superovulatory responses remains a particular obstacle to full exploitation of multiple ovulation embryo transfer (MOET) for genetic improvement through the female line. PMID- 1304028 TI - Control of ovarian function in cattle. AB - In cattle, ovarian function is controlled by complex local and systemic feedback mechanisms involving gonadotrophins from the pituitary gland and steroids and proteins from the ovaries. This control system ensures that in more than 96% of females, only one follicle will ovulate per oestrous cycle. Follicular growth and development in cattle occurs in a wave-like pattern, with two or three waves of follicles growing and regressing per oestrous cycle. Each wave is characterized by the emergence, from a pool of growing follicles, of a large dominant follicle which reaches a mature stage of development and may be induced to ovulate and form a functional corpus luteum with a single treatment of either human chorionic gonadotrophin (hCG) or gonadotrophin-releasing hormone (GnRH). The growth of this dominant follicle is associated with a marked reduction in both the number and growth of subordinate follicles in both ipsi- and contralateral ovaries, suggesting a systemic exertion of 'dominance'. The dominance concept is further supported by the observation that the subsequent wave of follicular growth cannot be detected until after the start of the regression of the previous dominant follicle. Furthermore, the dominance mechanism does not involve an action of inhibin, as previously proposed. In addition, in cattle, inhibin may not have a primary role in the control of follicle-stimulating hormone (FSH) release, unlike its role in other species such as sheep. Gonadotrophins provide the primary endocrine drive for the growth of follicles > 2 mm in diameter, but it is now becoming evident that other systemic and locally produced factors profoundly influence ovarian function. For example, short-term treatment of cattle with recombinant bovine somatotropin (BST) can double the number of small (< 5 mm) antral follicles without altering the pattern of circulating gonadotrophin concentrations. These follicles appear to be fully functional since they can be stimulated to develop further and ovulate with superovulatory treatment regimens. Dominance also appears to be exerted via a different pathway from that involved in the BST-induced recruitment of small follicles. The identification of the factor responsible for dominance, together with the elucidation of the mechanisms controlling follicular recruitment and growth should ensure that the full benefits ensuing from the precise control of ovarian function in cattle are achieved. PMID- 1304029 TI - The potential role of molecular genetic manipulation in the improvement of reproductive performance. AB - Revolutionary opportunities for the modification of animal performance are being created by the development of new methods for embryo manipulation and the application of molecular biology. This paper reviews the potential application of these procedures for the improvement of reproductive performance in livestock. There are three sections: a consideration of the methods of molecular manipulation that are available at present and those that seem likely to become available, a discussion of the modifications to hormonal systems and, finally, an analysis of candidate genes for manipulation of seasonality, number of ovulations, sex ratio and prenatal survival. The analysis points to a number of ways forward. Many of the most promising opportunities will depend upon the isolation of embryonic stem cells or the establishment of alternative methods of site-directed mutation. In most cases, the genes of interest have not yet been cloned and much remains to be learned about the molecular regulation of reproduction. A greater understanding seems likely to reveal the inadequacies of some of the present suggestions, but it is also certain to reveal further opportunities. However, in the longer term, there seems to be a real prospect of modification of at least some of these aspects of reproductive performance by molecular means. PMID- 1304031 TI - Endocrine manipulation--toxicological frontiers. AB - A variety of hormonal products has been developed for use in food animal production. Applications include therapy, particularly for fertility problems, zootechnical purposes comprising mainly the management of reproduction, for example the synchronization of oestrus, and the improvement of performance such as increased growth rate or increased milk yield. Although there is well established legislation both domestically and internationally for the registration of veterinary pharmaceutical products, hormones have become a special case at least to the public. This is particularly true when hormones are used to improve animal performance. The two notable issues to date have been the use of anabolic steroids as growth promoters and of bovine somatotrophin (BST) to increase milk yield in dairy cows. The high public profiles of these two issues have separately forced the introduction of new legislation in the EC, which will continue to have far-reaching implications for research and development in animal health and production for many years. This paper interprets recent developments in legislation concerning veterinary products and hormonal products in particular, giving examples of the toxicological assessment of four specific molecules and speculating upon the likely implications for the future practical exploitation of endocrine mechanisms in food animal production. PMID- 1304030 TI - Human contraception: development of new scientific opportunities. AB - Our current methods of contraception were largely developed in the 1950s and 1960s. Collectively these methods can limit population growth, although their acceptability at a personal level remains marginal. The number of abortions in the UK has risen progressively, from < 130,000 in 1980 to > 170,000 in 1990, and more people have sought sterilization. In global terms, population continues to increase on a scale unrecorded in human history. More than 800 million people, equal to the current population of North America, Europe and Japan, will be added to the world population of 5400 million by the year 2000, with 95% of the increase located in the economically and environmentally fragile regions of the South. Worldwide, in these 8 years, about 500 million abortions will be performed (> 40% by unsafe methods), about 80 million children under 1 year of age will die, and about 5 million women with be lost from pregnancy-related causes. Over 100 million people, most in Africa, Latin America, India and South-east Asia, will have become infected with human immunodeficiency virus. Religious, commercial and political pressures continue to constrain the development and distribution of contraceptive products, though some changes are in sight. Contraception is now being advanced in the broader context of neonatal and maternal health care. New scientific opportunities are also evident, with the potential to advance contraception in a quantal step. Third generation contraceptive steroids, anti-steroids, steroid-releasing vaginal rings, and injectable steroid preparations for men are all under clinical trial. Developments in the longer term, however, could hinge upon the greater specificity afforded by the manipulation of regulatory peptides. Agonists, antagonists and binding proteins for GnRH and the gonadotrophins are being investigated in an attempt to regulate the pituitary-gonadal axis more precisely. Inhibition of this axis may require the provision of low level steroid replacement, appropriately titrated to provide positive health care in the context of menstrual cyclicity, well-being, breast cancer and osteoporosis. Attempts are being made to identify and intercept the highly specific signals involved in fertilization and the maternal recognition of pregnancy, with the current clinical focus on the immunoneutralization of beta human chorionic gonadotrophin (beta hCG). More specific and more acceptable targets might include peptides involved in sperm-zona adhesion and sperm activation, sperm-oocyte fusion, and sperm-activated oocyte cleavage. The interception of these signals would prevent fertilization, implantation or both, and yet leave the hormonal profile of the menstrual cycle unchanged.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1304032 TI - Current concepts of folliculogenesis in monovular and polyovular farm species. AB - Follicular growth in sheep and pigs is under both endocrine and paracrine control, and the local factors involved include steroids, growth factors and other regulatory peptides such as the putative follicle regulatory protein. These factors can act either directly on ovarian cells, or by modulating the response to circulating gonadotrophins. It is suggested that during the early stages of development in sheep and pigs, follicles pass through a stage at which they are modulated by growth factors, after which endocrine control mechanisms become more important. There is evidence that interactions between follicle-stimulating hormone, insulin-like growth factor-1 and oestradiol further enhance development and steroidogenesis. Interfollicular relationships in polyovular pigs may differ from those in sheep, in that the more mature follicles may act to enhance development of the less mature in the selected population. Although it is unclear whether similar mechanisms operate in both hyperprolific pigs and prolific breeds of sheep, Meishan pigs and Booroola ewes do exhibit similar follicular characteristics compared with those of nonprolific breeds. The significance of this in relation to prolificacy requires further investigation. PMID- 1304033 TI - Control of synthesis and secretion of ovarian oxytocin in ruminants. AB - Increased expression of the oxytocin gene of ruminants is associated with the process of luteinization both in vivo and in vitro. Cell culture studies and measurements of mRNA in luteal extracts have confirmed that the gene is switched on in the preovulatory follicle about 24 h before ovulation, at the time of the gonadotrophin surge. It is downregulated again equally rapidly after ovulation, so that by day 2 of the cycle the capacity of the luteal cells to make oxytocin has already been greatly reduced. A number of factors can increase oxytocin production by luteinizing granulosa cells. They include oestradiol and compounds such as gonadotrophins and catecholamines which are known to act by increasing intracellular concentrations of adenylyl cyclase. However, all of these factors are ineffective if the follicle is collected too early, suggesting that an initial maturation step is necessary to develop responsiveness. Analysis of the promoter region of the bovine oxytocin gene has indicated that neither oestradiol nor cAMP can directly initiate activation; instead regulation appears to occur via a COUP factor binding site. Additional transacting nuclear proteins may therefore be required to act as intermediaries. The same factors that initially stimulate oxytocin production switch to inhibiting production shortly after ovulation, leading to downregulation of the gene. After translation of oxytocin mRNA during the luteal phase, oxytocin precursor is packaged into secretory granules in the large luteal cells. Processing involves a series of enzymatic steps, culminating in amidation to produce oxytocin. Cultured cells may secrete intermediate forms of partially processed peptide, but it is not known if this also occurs in vivo. Oxytocin release from the cell involves granule exocytosis which is probably triggered by an increase in intracellular calcium. During luteolysis this is regulated by the release of prostaglandin F2 alpha (PGF2 alpha) from the uterus, although additional factors may also contribute. Neither PGF2 alpha nor catecholamines appear to be prime regulators of luteal oxytocin release during the early and mid-luteal phases of the cycle and it remains to be determined how secretion is controlled at this time. PMID- 1304034 TI - Luteinizing hormone pulses, follicle-stimulating hormone and control of follicle selection in sheep. AB - The growth of large oestrogenic follicles that have the potential to ovulate if given an appropriate luteinizing hormone (LH) signal is dictated by the plasma concentration of follicle-stimulating hormone (FSH). Basal amounts of LH are essential for this FSH-induced follicle growth, but pulses of LH do not appear to be essential. The fall in FSH concentration during the follicular phase of the oestrous cycle in sheep, and the subsequent withdrawal of FSH from other developing follicles may not be sufficient to explain follicle selection. There is little evidence to support an active suppression of the growth of other follicles by a factor(s) produced by the dominant, or selected follicle. It is possible that LH pulses cause active atresia of non-selected follicles. The selected follicle is the one that can survive the fall in plasma FSH and the large increase in LH pulses during the follicular phase and selection may simply be a case of being the follicle(s) that is present at the correct time to receive adequate FSH and develop sufficiently to survive the inhibitory effects of LH pulses. Several mechanisms whereby LH pulses may inhibit follicle growth are suggested, and avenues for future research, particularly related to the expression of the LH receptor on granulosa cells of the developing follicle, are outlined. PMID- 1304036 TI - Work in slums by the Nursing Faculty of Christian Medical College and Hospital, Ludhiana: a report. PMID- 1304035 TI - Oxytocin and prostaglandin interactions in pregnancy and at parturition. AB - The demise of the corpus luteum is brought about by an interaction between ovarian oxytocin and uterine prostaglandin F2 alpha (PGF2 alpha) release in sheep. Indirect evidence suggests that a similar, but intra-ovarian, mechanism may also be involved in luteal regression in primates. During early pregnancy, a specific class of interferon (omega interferon) is released from the developing embryo in sheep and this interferon inhibits pulsatile release of uterine PGF2 alpha. Studies in ovariectomized, steroid-treated ewes indicate that conceptus secretory proteins inhibit pulsatile secretion of PGF2 alpha directly via an effect on prostaglandin synthesis and indirectly by maintaining plasma progesterone concentrations that inhibit the development of endometrial oxytocin receptors which normally occurs at the time of luteolysis. As pregnancy progresses, there is an increase in basal secretion of PGF2 alpha and PGE2 from the uterus into the fetal and maternal circulation. The release of maternal PGF2 alpha, but not PGE2, in response to oxytocin is also increased in late pregnancy. Endometrial oxytocin receptor concentrations follow a similar pattern, except at parturition where there appears to be downregulation of receptors. However, the release of PGF2 alpha in response to oxytocin remains high at this time and is further increased if the progesterone receptors are blocked with the anti progestin RU486. The dissociation between oxytocin receptor numbers and release of prostaglandins in response to oxytocin is also observed under other physiological situations, such as during seasonal anoestrus and after long-term ovariectomy, and requires further investigation. The role of oxytocin in the initiation of labour remains controversial. Although oxytocin concentrations in maternal and fetal plasma are not increased until parturition, uterine oxytocin receptor concentrations, uterine activity and maternal PGF2 alpha release in response to oxytocin are high in late pregnancy. Uterine activity and PG release is not altered by oxytocin in the fetal circulation at any stage of late gestation. We have used the oxytocin analogue CAP to investigate further the possible role of oxytocin in the initiation of labour. CAP can inhibit oxytocin induced PGF2 alpha release in cyclic sheep, at luteolysis, and in late pregnant sheep by binding to, and blocking, uterine oxytocin receptors. CAP does not inhibit basal fetal or maternal PGF2 alpha or PGE2 concentrations in late pregnancy or at parturition. CAP inhibits oxytocin-induced uterine activity and delays, but does not prevent, the increase in uterine activity associated with labour in this species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1304038 TI - Effective teaching and its application in nursing: problem solving method of teaching in nursing. PMID- 1304037 TI - Relevance of nursing curriculum for women, health and development. PMID- 1304039 TI - Understanding depression in India. PMID- 1304040 TI - The body fluid and nursing management of fluid therapy. PMID- 1304041 TI - Strengthening primary health care--a move towards privatisation. PMID- 1304042 TI - Faculty evaluation in nursing. PMID- 1304043 TI - Inter-country consultation on research in nursing. PMID- 1304044 TI - Trends in continuing education in U.K. PMID- 1304045 TI - The nurse. PMID- 1304046 TI - Women's knowledge, beliefs and health practices about breast cancer and breast self examination. PMID- 1304047 TI - Health status of nurses and yoga. V. Precision matching. PMID- 1304048 TI - Recent aspects in the use of liposomes in biotechnology and medicine. PMID- 1304049 TI - Lipids of lichens. PMID- 1304050 TI - Fatty acid degradation in plants. PMID- 1304051 TI - [General care of the multiple trauma patient]. PMID- 1304052 TI - [Surgical care of the multiple trauma patient]. PMID- 1304054 TI - [Rehabilitation and the multiple trauma patient]. PMID- 1304053 TI - [Postoperative care during the first few days: the main functions]. PMID- 1304055 TI - [Social consequences]. PMID- 1304056 TI - [Admission of the multiple trauma victim]. PMID- 1304057 TI - [The prevention of morbidity and mortality]. PMID- 1304058 TI - [Regulated hepatectomy. Left lobectomy]. PMID- 1304059 TI - [Central venous pressure]. PMID- 1304060 TI - [Scoliosis: definition and etiologies]. PMID- 1304061 TI - [Idiopathic scoliosis in the adolescent: indications]. PMID- 1304062 TI - [Surgery of scoliosis. Consultation before intervention]. PMID- 1304063 TI - [Hospitalization before the intervention]. PMID- 1304064 TI - [Reception by the operating room nurse]. PMID- 1304065 TI - [Care by the anesthesia specialist nurse]. PMID- 1304066 TI - [Postoperative course]. PMID- 1304068 TI - [Admission of a child following orthopedic surgery]. PMID- 1304067 TI - [Return from the operating room]. PMID- 1304069 TI - [Course after anterior access surgery]. PMID- 1304071 TI - [Conception and function of an orthopedic surgical suite: nurses' participation]. PMID- 1304070 TI - [Psychological repercussions of idiopathic scoliosis]. PMID- 1304072 TI - [Skin preparation in a child before an orthopedic intervention]. PMID- 1304073 TI - [Crisis in acute glaucoma]. PMID- 1304074 TI - [Cell separators for autologous transfusion]. PMID- 1304075 TI - [Regulated hepatectomies: right side hepatectomy]. PMID- 1304076 TI - [Anatomic reminder]. PMID- 1304077 TI - The effects of luminance on FPL and VEP acuity in human infants. AB - Grating acuity was measured in 16-week-old human infants. Three measurement techniques were used: forced-choice preferential-looking (FPL), and two visual evoked-potential (VEP) techniques. The stimuli were counterphase flickering sinewave gratings with a space-average luminance of -1.0 or 2.0 log cd/m2. Slightly different luminance-dependent changes occur between FPL and VEP acuities, suggesting that some factor influences the two methods differently as stimulus luminance varies. A comparison between FPL acuities and VEP acuities within infants suggests a quantitative relationship between techniques. Infant's acuity for sinewave gratings with a space-average luminance of -2.0, -1.0, 0.0, 1.0 and 2.0 log cd/m2 was also measured using a single VEP paradigm. The results are compared to the same measurements in adults and to infant and adult ideal observers. VEP acuity in this group of infants improves by about 0.5 log units between -2.0 and 0.0 log cd/m2 and remains asymptotic between 0.0 and 2.0 log cd/m2. This result suggests that luminance-dependent changes in infant acuity cannot be fully accounted for by immaturities in the optics and photoreceptor spacing and efficiency. PMID- 1304078 TI - Refractive state, corneal curvature, accommodative range and ocular anatomy of the Asian elephant (Elephas maximus). AB - The resting refractive state of six mature, female, Asian elephants (Elephas maximus) was determined using streak retinoscopy and neutralizing video retinoscopy. The amplitude of accommodation was also measured by neutralizing video retinoscopy of two animals and the corneal curvatures of three animals was measured by photokeratoscopy. The net spherical refraction was found to be +0.23 D. No difference was observed between cyclopleged and non-cyclopleged eyes (data from three animals), nor was there any difference between right and left eyes. Nine of the twelve eyes refracted had > or = 0.5 D astigmatism. The mean corneal power, as measured by photokeratometry was 21.3 D (SD = 1.8 D). There was a tendency towards with-the-rule corneal astigmatism in our sample (mean value: 1.2 D), though it did not reach statistical significance (P = 0.06). Two elephants were examined using neutralizing video photoretinoscopy. They were able to accommodate through 3 D. Three fixed eyes from three different elephants were obtained for gross and microscopic examination. The mean axial length of the eye was 38.75 mm and the lens had an axial diameter of approx. 10 mm. The posterior sclera was thick (8.0-8.5 mm). Histologically, the cornea was comprised of five distinct layers. A thin, meridionally oriented smooth ciliary muscle was identified. Individual muscle fibers were also observed associated with the posterior trabeculae of the uveal meshwork. PMID- 1304079 TI - Neurons immunoreactive to choline acetyltransferase in the turtle retina. AB - Light microscopic immunocytochemistry using anti-choline acetyltransferase (ChAT) was performed to stain putative cholinergic amacrine cells in turtle retina. ChAT immunoreactive somata lie in the inner nuclear (INL) and ganglion cell (GCL) layers. Three types of amacrine cells were found according to the location of their somata and their dendritic stratification pattern in the inner plexiform layer (IPL). Type I amacrines lie in the row of cells closest to the INL/IPL limits and they branch along the s1/s2 border of the IPL. Type II amacrines are displaced to the GCL and they ramify along the s3/s4 border of the IPL. Type III amacrines lie in the middle of the INL, 2-3 rows away from the IPL limits and their dendrites appear to be bi- or tri-stratified in s1 and s3-s4 of the IPL. The turtle ChAT-IR amacrines are thus similar to the types described in chicken retina. A regular, non-random mosaic formed by stained type II amacrine cells was observed in the GCL. Their density in mid-central retina was 750 cells/mm2, tapering off to 393 cells/mm2 in peripheral retina. Our study indicates that a pair of cholinergic amacrine cell types in turtle retina is arranged in mirror image symmetry contributing to sublamina "a" and sublamina "b" of the IPL, like in other vertebrate retinas. PMID- 1304080 TI - Opponent-processing effects on the field spectral sensitivity of pattern-elicited electroretinograms. AB - Field spectral sensitivities of the pattern-elicited electroretinogram (PERG) were obtained from two subjects using a modified version of Stiles' two-color increment threshold procedure. A 540 nm checkerboard test pattern of 38 degrees dia was alternated at 8 Hz on a uniform adapting field of the same size. Test intensity, field wavelength and field intensity were varied parametrically. The derived field spectral sensitivity does not resemble that of any individual class of cones; it roughly approximates the photopic luminosity function V lambda, but with sensitivity dips at 540 and 600 nm, which may be associated with an adaptation of the red/green (R/G) opponent site. Thus, it is proposed that the PERG reflect activities in both the luminance and the R/G opponent channels. PMID- 1304081 TI - Temporal frequency dependent adaptation at the level of the outer retina in humans. AB - The focal electroretinogram (FERG) was used to examine temporal frequency tuning at the outer retinal level in humans by measuring temporal modulation thresholds. Changes in FERG thresholds as a function of ambient light level were compared to temporal modulation thresholds obtained psychophysically using the same stimuli. At lower temporal frequencies, both FERG and psychophysical thresholds changed sensitivity proportional to the mean illuminance level. At higher illuminance levels, both threshold measures were relatively independent of illuminance. The comparison of the FERG to the behavioral data suggest that most of the adaptation dependent changes in temporal sensitivity in humans occur at the level of the photoreceptor complex. PMID- 1304082 TI - Rapid and slow changes in the human cone electroretinogram during light and dark adaptation. AB - Changes in the response characteristics of the human cone electroretinogram (ERG) during light and dark adaptation were studied in two visually normal subjects. Cone ERG responses were isolated under all adaptation conditions through the use of 31 Hz flicker. To determine the time-course of changes in the cone ERG during adaptation, responses to stimuli of constant luminance were measured repeatedly during 15 min of exposure to an adapting field of 2.0 log cd/m2 and during 30 min of dark adaptation following adapting field termination. In addition, luminance response functions were obtained before and immediately after adapting field onset, as well as before and immediately after adapting field termination. The results indicate that the human cone ERG is influenced by two major processes. One process has a relatively rapid time-course and serves to reposition the luminance-response function along the luminance axis following changes in ambient light levels. The second process, which has a slow time-course, scales response amplitudes during light and dark adaptation by the same proportion at all stimulus luminances. The results provide a framework for predicting the manner in which the cone ERG will change with alterations in the state of retinal adaptation. PMID- 1304083 TI - Rotation of Listing's plane during vergence. AB - When visually fixating targets on an isovergence surface, the position of each eye was constrained to a plane. Thus, Listing's law holds during vergence. The planes were, however, rotated temporally with respect to those when viewing distant targets. The effect of this rotation was to produce a torsion which depended on eye elevation; extorsion of the two eyes for downward gaze and intorsion for upward gaze. The saccadic velocity command was relatively unaffected during vergence. Computer simulations suggest that the saccadic tonic command and the vergence command interact multiplicatively in three dimensions. PMID- 1304084 TI - The effects of prolonged temporal modulation on the differential response of color mechanisms. AB - The identification of three independent cardinal directions in color space suggests the existence of three independent post-receptoral mechanisms that can be desensitized by habituation to a temporally modulated light. In this paper, the differential response of each cardinal mechanism is estimated over a range of inputs before and after habituation. Simple mathematical considerations show that the threshold elevations following temporal modulation are not consistent with multiplicative gain changes; rather, these elevations require a change in the shape of each cardinal mechanism's response function. With this method, the effects of habituation can also be differentiated from the effects of a change in the steady adapting light. PMID- 1304085 TI - Chromatic adaptation to natural and incandescent illuminants. AB - A color CRT image display system was used to present adapting backgrounds that were spatially and temporally varied. Three observers adjusted the chromaticity of test stimuli to produce an achromatic appearance under a variety of adapting conditions. The achromatic-appearing chromaticities were used as measures of the observers' states of chromatic adaptation. The spatial configuration of the adapting background was varied to measure the spatial extent of the mechanisms responsible for chromatic adaptation. The temporal configuration of the adapting background was varied to measure the time-course of these mechanisms. The results show that chromatic adaptation is spatially localized with a time-course on the order of 10 sec. Since the mechanisms were shown to be spatially localized, the observed temporal integration across eye movements is required to allow these mechanisms to adjust to the spatially integrated scene chromaticity. PMID- 1304087 TI - Visual resolution of motion ambiguity with periodic luminance- and contrast domain stimuli. AB - Visual motion processes were studied with luminance- and contrast-modulated gratings. A sine-wave luminance grating was displaced abruptly back and forth by 3/16 cycle. The display sequence is ambiguous in that each 3/16-cycle phase shift (short-path motion) could just as readily be seen as a 13/16-cycle shift (long path motion) in the opposite direction. By varying the duration of the interval (IFI) between the two phase positions, the luminance of the IFI, or the spatial frequency of the grating, it was possible to bias the ambiguous percept in favor of short-path motions or long-path motions. A contrast-modulated grating displaced through 3/16 cycle always appeared t undergo short-path motion. Current motion models which incorporate Reichardt-type/energy mechanisms and certain types of auxiliary signal transformations which precede those mechanisms do not adequately explain the effects of IFI intensity on the perceived motion of a sinusoidal grating or the effect of IFI duration on the perceived motion of a contrast-modulated grating. PMID- 1304086 TI - Reaction time distributions and their relationship to the transient/sustained nature of the neural discharge. AB - Reaction time distributions (RTDs) were determined in response to near-threshold increments of long duration. Stimulus parameters were selected to isolate the chromatic and achromatic systems. The RTDs for the achromatic system peak sooner and are more narrow than those obtained for the chromatic system. These results are analyzed in terms of the neural discharge pattern of parvo and magno pathways. PMID- 1304088 TI - A bidimensional theory of achromatic color vision. AB - The theory is based on a perceptive color system where the achromatic colors are specified by their degree of similarity to the three qualities white, black and luminous. Black and luminous are treated as opponent variables. It is assumed that white and luminous/black are determined by different kinds of visual processes termed the w- and the b-process. The relationship between these processes and luminance parameters in a simple disc/ring configuration is derived from available data. The b-process is related to stimulus contrast in a simple manner. It is assumed to involve cells with antagonistic center/surround organization of the receptive field. The w-process is primarily determined by the local luminance, and it is assumed to involve cells that lack a center/surround organization of the receptive field. The w-process has properties similar to the processes involved in chromatic color vision. The theory can account for different kinds of psychophysical data on achromatic colors like data on simultaneous contrast, color scaling, and color constancy. PMID- 1304089 TI - The effect of pupil size on chromostereopsis and chromatic diplopia: interaction between the Stiles-Crawford effect and chromatic aberrations. AB - Several studies have reported that the magnitude of chromostereopsis changes as the pupil size changes. Einthoven's theory, that chromostereopsis is determined by interocular differences of monocular transverse chromatic aberration, can not easily explain this change. Therefore, several alternative hypotheses have been introduced, most notably by Vos [(1960) Vision Research, 6, 105-107], who argues that shifts in chromostereopsis with pupil size are due to decentration of the peak of the Stiles-Crawford effect (SCE) with respect to the pupil. We tested this hypothesis by measuring chromostereopsis under both scotopic (no SCE) and photopic conditions with centered and decentered artificial pupils. The results show that the SCE plays an important role in the effect of pupil size on chromostereopsis. Similar changes were also measured in monocular chromatic diplopia which supports the hypothesis that the effect of pupil size on chromostereopsis is due to monocular mechanisms. PMID- 1304090 TI - Changes in pattern induced flicker colors are mediated by the blue-yellow opponent process. AB - The colors of Benham's Top [pattern induced flicker colors (PIFCs)] were matched with color stimuli provided by a computer aided color mixer. Subjects viewed a series of specifically modified black and white disks and matched the resulting subjective color with a comparison field containing the color generated by additive mixing. Different phase relations between the apparently colored ring and the surround were tested. The color loci of all PIFCs were found to lie on a plane in receptor three-space which is given by the axis of the shortwave receptor excitation and a vector given by combining the middle and long wave receptor excitation directions in a fixed ratio of nearly 1:1. From the orientation of this plane it can be deduced that the blue-yellow opponent process (the blue-on-center cells) alone accounts for the different PIFCs. PMID- 1304091 TI - Binocular integration of contrast information in amblyopia. AB - We asked whether suppression in amblyopia could be accounted for by dichoptic masking as described in normals, operating in the presence of a contrast threshold difference between the two eyes. A dichoptic masking paradigm was employed to investigate binocular interaction in a mixed group of amblyopic subjects. Normal dichoptic masking was not seen after threshold differences between the two eyes were accounted for in the majority of subjects studied. We found that the binocular dysfunction did not merely follow as a consequence of the known monocular loss and that it depended upon the aetiology of the amblyopia and the spatial frequency of the stimulus. PMID- 1304092 TI - The role of saccades in the perception of texture patterns. AB - We studied the perception of texture patterns when observers used saccadic eye movements to scan the display and when the line of sight was maintained in the display center without saccades. Saccades improved the discrimination of the size and the shape of a central randomly-shaped polygon for display durations > 1 sec. Saccades were more important with textures that did not readily segregate into target and background regions than with those that did. Directing saccades to the curvature extrema of the central target figure was more useful than directing them elsewhere. Saccades did not enhance texture segregation, but rather improved the discriminability of individual target and background elements by overcoming lateral interference. To the extent that strong lateral interference is inevitable with poorly-segregating textures, our results show that serial inspection is best carried out by sequences of saccades, not by sequences of attention shifts. PMID- 1304093 TI - Color discrimination and adaptation. AB - We have measured color discrimination in the isoluminant plane under rigorously controlled adaptation conditions. Two regimes were studied. Under the first regime the observer was adapted to the region of color space in which the discriminations were made. Thresholds for detecting changes along the S-(L + M) axis are a linearly increasing function of the excitation of the S cones. Thresholds for detecting changes along the L-M axis are independent of the locus of adaptation along this axis. The straightness of these functions is inconsistent with the theory that second stage mechanisms are more sensitive in the middle of their operating ranges. No convincing evidence of interactions in the effects of adaptation locus or test stimuli was observed. Under the second regime the observer was adapted to one point in color space and the stimuli to be discriminated were located in other places in color space. Discrimination seems to be limited primarily by mechanisms maximally sensitive to modulation along the isoluminant cardinal axes but evidence suggestive of the operation of higher order mechanisms was also found. PMID- 1304094 TI - Extrapolation of linear motion. AB - We investigated observers' ability to extrapolate a linear trajectory of a moving point, in order to determine how effectively the visual system can combine orientation and position information for moving stimuli. Observers saw a probe dot moving along a straight line toward a stationary target dot. The probe dot extinguished before reaching the target, and the observers' task was to judge whether an extrapolation of the trajectory of the probe would pass to the left or right of the target. Performance was measured as a function of probe velocity, length of the visible trajectory, and location of the target. The empirical results indicated that over a range of conditions, performance on this task is qualitatively similar to, but somewhat less accurate than, that on an analogous task with static stimuli. A four-component model is presented to account for the results. The model specifies an accurate extraction of probe motion parameters, extrapolation of the motion by an ideal observer, and limitations on the input to these processes in the form of visual field spatial inhomogeneity and temporal decay of position information. PMID- 1304095 TI - Two movement aftereffects: evidence for luminance- and color-movement pathways. AB - Two movement aftereffects (MAEs) that bear closely on the issue of visual processing of color and movement have been isolated. Following adaptation with a vertical luminance stimulus a strong MAE occurred with the same stationary test stimulus oriented horizontally and also in a perfectly uniform field. Neither effect occurred following adaptation with a color equiluminance stimulus. These aftereffects have not been reported before. It is concluded that there are at least three pathways for movement, a color, a color-plus-luminance, and a luminance pathway. PMID- 1304096 TI - Errorless performance in a two-frame apparent motion task using high contrast stimuli, a failure to replicate Cleary (1990) PMID- 1304097 TI - Ambiguous motion in a two-frame sequence. AB - We measured the ability of ten different observers to identify the direction of motion displacement of a 1.77 c/deg grating in a two-frame sequence. One subject showed virtually errorless performance, in agreement with Derrington and Cox [(1992) Vision Research, 32, 2191-2193], but most subjects found the task difficult and made many errors. One subject saw motion in the reverse of the actual direction of displacement. We conclude that the two-frame sequence contains motion signals in both directions, and that selective attention to the forward direction is necessary for errorless performance. PMID- 1304098 TI - [Nasal and sinusal polyposis. Semiology and values of magnetic resonance imaging]. AB - Twelve patients with nasal polyposis were examined with magnetic resonance imaging (MRI) prior to surgical ethmoidectomies (20 ethmoidectomies). MRI signal was analyzed in correlation with surgical findings in order to define the semiology of nasal and sinuses polyps. One of the most important point of this semiology is based on the analysis of sequences after administration of gadolinium. MRI seems an interesting method for analysing the extension of nasal polyposis and could be useful for ENT surgeons before an endoscopic nasal surgery. PMID- 1304099 TI - [Brush technique in cytological analysis of the nasal mucosa. A critical and comparative analysis]. AB - The cytological study of the nasal mucosa is one the essential steps toward a better understanding of the physicopathological mechanisms involved in chronic affections of the nose. The development of a reliable, reproducible noninvasive technique to obtain cells in the prerequisite for this analysis. The brush technique is based on the use of a small cylindric nylon brush which is rotated as it is moved back and forth across the nasal mucosa to harvest the various cell types present on the surface of the mucosa. The specimen obtained is centrifuged and examined under an optical microscope. A semi-quantitative analysis is carried out to determine the relative richness of the specimen in epithelial cells (ciliated, qoblet and basal cells) and in inflammatory cells (neutrophils, basophils, eosinophils, lymphocytes, and monocytes). A precise differential cell count is then performed. According to the results obtained, an immunologic marker study of lymphocyte subsets may also be done using the same specimen. This technique may be used in both children and adults and permits cell harvest from various sites within the nasal fossa. Already tested in the study of the activity of cilia, this method is promising for the cytological study of the nasal mucosa. The brush method and other techniques of cell harvest are described and compared. PMID- 1304100 TI - [Inverted papilloma of the nose and paranasal sinuses. Retrospective study of 18 cases]. AB - The authors report about 18 cases of inverted papillomas treated between 1981 and 1991. The average age of the patients is 51 years, with a marked male predominance. The average follow-up is of 4 years. The most often noted revealing sign is unilateral nasal obstruction. A history of polypectomy and nasosinual surgery is found in 45% of the cases in our series. The treatment was surgical in all cases, including 4 De Lima's procedures, 11 procedures through a paralateronasal approach, 2 ethmoidectomies through an endonasal approach, and 1 degloving for a septal lesion. Endonasal surgery was performed for two limited tumors, for which the diagnosis of inverted papilloma never could be made preoperatively. The recurrence rate observed in our series is 5%. Out of 18 patients, 4 presented with a malignant change, either at once (2 cases) or some time after the primary exeresis of the inverted papilloma (2 cases). In the light of the results, and after analyzing the literature, the authors reassert the necessity of radical exeresis for inverted papilloma. Rhinosinual endoscopy must remain a diagnostic means and never is an indication of exeresis of inverted papilloma. The authors emphasize the difficulty of the histological diagnosis and set forth the various problems arising from the malignant degeneration of inverted papillomas. Recent discoveries on viral etiopathogenesis and on the oncogenic potential of the type-16 papilloma virus may allow characterizing the evolutive and prognostic features of inverted papillomas in the future. PMID- 1304101 TI - [Retrospective study of 139 cases of epidermoid carcinoma of the upper respiratory and digestive tracts treated by induction chemotherapy with cisplatin 5FU. Influence of the result on the therapeutic protocol]. AB - A retrospective study of 139 untreated staged III and IV epidermoid carcinomas of the upper aero digestive tract is reported concerning oropharynx, oral cavity, hypopharynx and larynx, all of them received as a first treatment, chemotherapy using a five days course of Cisplatinium (20 mg/m2/D) and 5FU (1,000 mg/m2/D). The aim of the trial was to determine: a) a free of disease survival and a global survival rate's increase, b) a more conservative treatment. The results of chemotherapy were clinically evaluated in two groups: Responders (a total or a more than 50% response), and no responders. The results were: on the tumor site: 64% responders (25% total response)--more in smaller lesion; on the lymphatic nodes: 54% responders (more in N1-N2). The results vary in inverse ratio to the stage of the lesion; usually, 2 cycles of chemotherapy are used but in case of efficiency: 2 to 6 cycles are provided increasing to 20% the rate of the total responders; toxicity of the drugs was neligible: 6 cases, 3 of them were renal insufficiency. The global survival rate at 3 months reaches 56.7%. The median line of survival reaches 32 months in responders reverse 15 months (NR); but there are no significant difference between the two groups concerning the recurrences, or the metastasis. The local treatment (after chemotherapy) decided in the 137 patients was surgery, in 40 cases and radiotherapy, in 97 cases (conservative treatment; 80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304102 TI - [Vestibular evoked potentials. Diagnostic trends]. AB - The contribution of short-latency evoked potentials to the exploration of auditory, visual and somatosensory neurosensory pathways is capital. The determination of short-latency vestibular evoked potentials has encountered many difficulties, mainly due to the necessity to find a specific, very short stimulation in order to select and synchronize the vestibular nerve fibers. Recent studies in animals have demonstrated short-latency potentials evoked by angular accelerations, linear accelerations or electric shocks on the round window. The generators of these potentials seem to be located in the vestibular nerve and nuclei. Electric stimulations of the internal ear have the advantage of providing a study of the peripheral vestibular pathways separately on both sides, while accelerations involve both vestibula, which probably makes the interpretation of data very difficult. PMID- 1304103 TI - [Acoustic distorsion products. A systematic analysis of technical parameters. How to explain the results?]. AB - The aim of this study was to define the most interesting parameters useful for a clinical application of acoustic distortion products (mainly, F1 and F2 primaries frequencies and levels). The most interesting F1 and F2 primaries level in order to separate subjects with a normally-hearing function and patients with a sensorineural hearing loss is 50 dBHL. This result can be explained by some physiological properties of cochlear mechanisms. PMID- 1304105 TI - [Special issue: Renal tumors]. PMID- 1304104 TI - [Use of cultures of human thyroid cells in physiopathology and pharmacotoxicology]. AB - We reconstituted functional follicles from isolated cells, after embedding in a collagen matrix. Therefore we could carry out many investigations. We showed that the cells embedded in collagen reorganized into functional follicles secreting thyroglobulin (Tg) visualised in the intra-follicular compartment, and triiodothyronine (T3) after TSH stimulation. We used these reconstituted follicles for testing several drugs, amiodarone, propranolol and some anaesthetic drugs (thiopental, midazolam and ketamine). We observed that all these drugs inhibited partially or totally, according to the dose administered, the follicular production of Tg and T3. We also found that the follicles reconstituted from thyroid Grave's tissues gave an abnormal secretion of Tg and T3. Finally we created in Rennes a human thyroid model that permits the exploration of pathologic tissues and that may be used in pharmacotoxicology. PMID- 1304106 TI - [Why a special issue on tumors of the kidney?]. PMID- 1304107 TI - [Place of partial nephrectomy in surgery of tumors of the kidney]. AB - Partial nephrectomy for a small renal tumor is usually technically possible, especially in the case of polar tumors, but it does not ensure the same degree of therapeutic safety as radical nephrectomy. At the present time, it is preferable to restrict this technique to tumors in a solitary kidney, when possible, and to benign tumors and tumors less than 3 cm in subjects over the age of 50 years, when the contralateral kidney is healthy. PMID- 1304108 TI - [Why and how to grade renal carcinomas?]. AB - The prognosis of renal cell carcinomas has been a controversial subject for pathologists for a long time. At the present time, in addition to stage, the nuclear grade defined by Fuhrman represents an essential element in the prognostic assessment. A renal cell carcinoma can be easily characterized by its stage and its grade, defining a precise prognosis. Specific entities such as tubulopapillary tumors, oncocytomas and chromophobe cell carcinomas must also be graded until the results of complementary studies become available allowing a better assessment of their autonomy among renal cell carcinomas. PMID- 1304109 TI - [Oncocytomas of the kidney. Analysis of current knowledge and creation of a study group]. AB - Typical oncocytomas are easily recognized. Nevertheless, in recent years, some cases of atypical oncocytomas much more difficult to identify, have been published in French and English medical literature. To further complicate the matter, the tumors are sometimes described as benign and sometimes as malignant. To try to clarify such discrepancies, this article will first set forth the current knowledge, and second provide the basis for a subsequent study designed to simultaneously resolve the histologic and prognostic dilemma. PMID- 1304110 TI - [Is it useful to isolate a chromophobe cell variant among carcinomas of the kidney?]. AB - Chromophobe cell carcinoma is a little known variety of renal cell carcinoma representing 7 to 9% of all renal tumors. This tumor is confused with either clear cell carcinoma (clear subvariety) or oncocytoma (eosinophilic subvariety). Until ultrastructural and prospective studies of the prognosis of this tumor become available, it already seems important to perform colloidal iron staining to establish the differential diagnosis between oncocytoma and chromophobe cell carcinoma. PMID- 1304111 TI - [Cystic clear cell tumors of the kidney]. AB - Renal clear cell carcinoma can sometimes present as: unilocular cyst; necrotic pseudocyst; multilocular cyst, resembling cystic nephroma. Diagnosis by cytology and on frozen sections is often difficult, or even impossible. PMID- 1304112 TI - [Tubulo-papillary tumors of the kidney. A distinct entity with a discussed prognosis]. AB - Tubulopapillary tumors of the kidney represent a group of peculiar interest with specific histological and cytogenetic features. These tumors are distinguished from other renal tumors by their more favorable prognosis. PMID- 1304113 TI - [Urothelial tumors of the kidney]. AB - Urothelial tumors of the kidney arise from the urothelium of the renal pelvis. Most of them are transitional cell carcinomas histologically similar to bladder carcinomas. The new staging system emphasizes the role of kidney parenchyma in the spread of the tumor. Homolateral multifocal lesions are frequent, along with bladder lesions, preceding, simultaneous with or subsequent to upper tract tumor. PMID- 1304114 TI - [Primary epidermoid carcinoma of the kidney pelvis. Characteristics in relation to urothelial carcinomas and review of the literature apropos of a case]. AB - Primary renal squamous cell carcinoma is rare. Its histological is not very difficult, but this case report emphasizes the most important diagnostic criteria and defines the frequency clinical course and clinical findings of these tumors. PMID- 1304115 TI - [Bellini duct carcinoma or kidney collecting duct carcinoma]. AB - The authors report a case of renal collecting duct carcinoma or Bellini duct carcinoma. This rare variety of renal carcinoma, which usually has a poor prognosis, is situated in the renal medulla and pyramid. It is composed of large cells similar to collecting duct cells and can be seen at a distance from the tumor. These cells are arranged in highly suggestive tubular, microcystic and papillary structures. These morphological data are compared with those reported in the literature. PMID- 1304116 TI - [Primary carcinoid tumor of the kidney. Apropos of a case with immunohistochemical study]. AB - The authors report a case of primary renal carcinoid in a 57-year-old woman in whom the diagnosis, established by histological findings, was confirmed by argyrophilia and immunohistochemical studies using anti-neuron-specific enolase, chromogranin A, serotonin and somatostatin antibodies. The clinical and pathological features of this rare renal tumor are discussed. PMID- 1304118 TI - [Analysis of DNA of renal cell carcinomas by flow cytometry]. AB - Flow cytometry DNA analysis of fragments of fresh or paraffin-embedded tumor was performed in order to investigate its prognostic value in renal cell carcinoma. As aneuploidy is a frequent cytogenetic finding of these cancers, it is not surprising that the literature reports a high incidence of anomalies of DNA content, affecting 2/3 of cases studied. DNA aneuploidy is more frequent in advanced stages, high grades and spindle-cell carcinomas. Its prognostic value in terms of the survival of nephrectomized patients has been demonstrated by unifactorial studies. Several studies using Cox's model have demonstrated its independence of stage and grade, but they are too limited for DNA ploidy to be considered to be an element of the therapeutic decision. In contrast with other sites, the prognostic influence of the proliferation evaluated by S% does not appear to be as important as DNA ploidy. Prospective studies comparing these results should take into account the tumor heterogeneity observed in this type of cancer by analysing, for example, several fragments of the same tumor. PMID- 1304117 TI - [Genetic aspects of renal tumors in adults]. AB - The aetiopathogenesis of adult renal tumors is poorly understood. The specific chromosomal changes detected by the study of tumor karyotypes suggest a cascade of oncogene activation and tumor suppressor gene inactivation in the course of renal carcinogenesis. These cytogenetic studies have isolated two entities: non papillary carcinomas (clear cell and/or eosinophil carcinomas) and tubulopapillary tumors (cortical adenoma, basophil papillary carcinoma). Specific changes of the short arm of chromosome 3 are observed in 70 to 85% of cases of clear cell carcinomas, while trisomy 17 is detected in 70% of cases of tubulopapillary tumors. Cytogenetics is also able to distinguish low and high grade malignant tubulopapillary carcinomas. Limited data are available at the present time concerning oncocytomas. PMID- 1304119 TI - [Rhabdoid tumor of the kidney]. AB - The clinical and pathological features of a rhabdoid tumor of the kidney in a 4 month boy are presented. The precise diagnostic criteria (light and electron microscopy, immunohistochemistry) of this rare and usually unresponsive and rapidly fatal tumor are underlined. PMID- 1304120 TI - [Production of griseoviridin and etamycin by the new culture, Streptomyces albolongus]. AB - An actinomycete strain designated as 4297 was isolated from a soil sample collected near Moscow. The strain produced a complex of two antibiotics. One of them had a broad antibacterial spectrum and, in terms of its physicochemical properties and X-ray structural evidence, was identified with griseoviridin. The other was active against gram-positive bacteria and, by its chromatographic comparison with an authentic sample, mass spectroscopic determination of the molecular weight and UV spectra, was identified with etamycin. The strain 4297 differed from the described cultures producing griseoviridin and etamycin. By the taxonomic features it was classified as belonging to Streptomyces albolongus. PMID- 1304121 TI - [Resistance of the strain Streptomyces hygroscopicus 155 to autogenous and other antibiotics]. AB - Streptomyces hygroscopicus 155, a strain producing pandavir (nigericin) and azalomycin, was studied with respect to resistance to its own and some other antibiotics i.e. tetracycline, gentamicin, streptomycin, erythromycin, tylosin, thiostreptone, benzylpenicillin, monensin and salinomycin. An inactive variant of the culture was used in the control. PMID- 1304122 TI - [Preparation and regeneration of protoplasts of the strain Streptomyces hygroscopicus 155]. AB - Protoplasts of Streptomyces hygroscopicus 155 producing nigericin, a polyether antibiotic, were prepared. Conditions for protoplasting and optimal concentrations of lysozyme and glycine, and the age of mycelium were studied. With the method of the experiment design, concentrations of four components: CaCl2, MgCl2, KH2PO4 and TES buffer in the regeneration medium were determined. The levels of CaCl2 and TES buffer proved to be the most important parameters. PMID- 1304123 TI - [Selection of Penicillium chrysogenum--producer of penicillin with several valuable technologic features]. AB - The efficiency of the routine methods for improvement of P. chrysogenum providing specific selection by several features with testing one of them was studied. A new highly potent strain of P. chrysogenum producing phenoxymethylpenicillin was isolated. The strain is characterized by a shorter fermentation cycle, lower viscosity of the fermentation broth and capacity for synthesizing 32,600 units/ml of phenoxymethylpenicillin under industrial conditions (in a lactose medium) by the 97th hour of the cultivation in fermenters with energy consumption of 1.3 kW. The increased amylolytic activity of the strain and the decreased viscosity of the fermentation broth provided using of the fermentation media containing 3.5 per cent of corn meal. PMID- 1304124 TI - [Immunomodulating action of peptidoglycan of microbial origin]. AB - The action of a high molecular weight peptidoglycan produced by Agrobacter radiobacter sp. on the functional activity parameters in leukocytes and macrophages i. e. chemotaxis and adhesion was studied. It was shown that the peptidoglycan had a stimulating action on the chemotaxis of cells of the peritoneal exudate. A marked stimulating action of the drug on the primary immune response to the tissue antigen of sheep erythrocytes was observed. The peptidoglycan stimulated the antibody titers and delayed hypersensitivity when administered in various periods after an antigenic stimulus. Multifactorial experiments on the protective action of the peptidoglycan in experimental infections were carried out. Second-order polynomial statistic models characterizing the animal survival rate were constructed and the dose-time parameters of the drug use were optimized. PMID- 1304125 TI - [Basis for development of biocatalytic processes for transformation and synthesis of beta-lactam antibiotics]. PMID- 1304126 TI - [Inactivating action of bacteria on the lipolytic activity of solizyme and its prevention by antibacterial drugs]. AB - Bacteria capable of producing exoproteases were isolated from intermediate products of microbial lipase. The proteolytic enzymes produced by the bacteria were able to inactivate 20 to 80 per cent of the lipase depending on the time of incubation, protease production by the contaminating microbe and the experimental conditions. Antibiotics and antiseptics inhibiting growth of bacteria prevented or limited their inactivating action on lipase. Except catamine, the tested antimicrobial drugs as such had no effect on lipase activity. PMID- 1304127 TI - [Sensitivity of microflora isolated in the process of preparing solizyme to antimicrobial drugs]. AB - Microorganisms isolated from intermediate products of microbial lipase (solysime) and auxiliary raw materials, reagents and water used in the production of the enzyme belonged to diverse taxonomic groups. They were mainly susceptible to antibiotics (aminoglycosides, rifampicin, chloramphenicol and others) as well as to antiseptics and chemotherapeutics. However, certain isolates were moderately resistant to some of the antimicrobial agents (they were more frequent among Pseudomonas spp.). The bacteriostatic action of many of the drugs was more pronounced than the bactericidal one. It was especially evident after increasing of the microbial load (from 10(5) to 10(8) CFU/ml). At a temperature of 10 degrees C against 37 degrees C the susceptibility of the cultures to the bactericidal action of the drugs usually decreased. PMID- 1304128 TI - [Resistance of hospital strains of microorganisms to antibiotics and antiseptics]. AB - The development of resistance of collection and freshly isolated S. aureus and C. albicans strains to the antiseptic decamethoxim and an original diarylcyclohexane derivative was studied comparatively in vitro. It was shown that the rate of the resistance development was low. After 20 subcultures in the presence of increasing concentrations of decamethoxin, its sensitivity of S. aureus and C. albicans decreased 16-32 and 16-fold respectively. After 20 subcultures in the presence of increasing doses of the diarylcyclohexane derivative, its sensitivity S. aureus and C. albicans decreased 4- and 4-8-fold, respectively. It was found that in the hospital strains of S. aureus and C. albicans, the antibiotic resistance and sensitivity to decamethoxin and the diarylcyclohexane remained high, which indicated that there was no cross resistance to these compounds in the strains studied. PMID- 1304129 TI - [Conjugative R plasmids isolated from hospital strains of Pseudomonas aeruginosa]. AB - It was shown that Pseudomonas aeruginosa hospital strains isolated from patients and environment in the Republican Centre of Burns in Tbilisi contained conjugative R plasmids. The plasmids were marked pM15 and pM19, respectively. The plasmid pM15 determined resistance to carbenicillin, kanamycin and tetracycline and plasmid pM19 determined resistance to carbenicillin, kanamycin, tetracycline, chloramphenicol, gentamicin and streptomycin. Plasmid pM15 had a molecular weight of 45.8 MD and seven sites for EcoRI, six sites for HindIII and five sites for Hpa-I-restrictase. This plasmid, as others, belongs to the Inc-P1 incompatibility group. PMID- 1304130 TI - [Immunomodulating properties of various microbes--representatives of normal intestinal microflora]. AB - The impact of oral administration of heat-killed bifidobacteria, lactobacteria, enterococci and bacteroides on mouse resistance to experimental salmonellosis and content of immunoglobulin-synthesizing cells in the proper plate of the small intestine was studied. It was shown that the administration of the killed bifidobacteria, lactobacteria and enterococci increased the animal resistance to experimental salmonellosis infection and induced an increase in the content of immunoglobulin-synthesizing cells in the proper plate of the small intestine. The administration of the killed bacteroides had no such effect. Possible development of bacterial preparations with immunomodulating properties based on killed bifidobacteria, lactobacteria or enterococci is discussed. PMID- 1304131 TI - [Combined action of doxycycline and mytilan on the immune response to tularemia antigen]. AB - Combined action of doxycycline and mytilan, a natural polysaccharide, on the primary immune response to the antigen of the tularemia vaccinal strain in CBA mice was studied. The polysaccharide was used to compensate the immunosuppressive effect of doxycycline high doses on the humoral immune response. The maximum stimulation of the antibody titers as compared to the controls (more than 250 per cent) was observed when mytilan was administered simultaneously with or prophylactically 3 days prior to the antibiotic in doses of 2.5 and 25 mg/kg. The use of mytilan in combination with doxycycline high doses made it possible to compensate the antibiotic-induced decrease of DTH and even to stimulate it as compared to the controls. The highest levels of DTH (150 per cent against the control) were observed when mytilan was administered prophylactically in doses of 2.5 and 11.25 mg/kg 3 days prior to immunization. Mytilan had the highest stimulating effect on antibody production. The combined use of doxycycline and mytilan was characterized by significant stimulation of antibody production and DTH when the dose/time regimens were rational. PMID- 1304133 TI - [Comparative effectiveness of antimicrobial action of antiseptics against pathogens of chronic purulent otitis media]. AB - Comparable antimicrobial and disinfecting action of decamethoxine and silver preparations on pathogens of chronic purulent otitis media (CPOM) was studied. The clinical isolates of staphylococci proved to be most sensitive to decamethoxine whose MBcC conformed to 16.5 micrograms/ml. The antimicrobial action on Proteus spp. and Pseudomonas aeruginosa was less pronounced. The required concentrations for bactericidal action on these pathogens were 69 and 93.5 micrograms/ml, respectively. The antimicrobial activity of the silver preparations such as poviargol, collargol and protargol was low. Depending on the microbial species, the bactericidal effect of the silver preparations was 12-235 times lower than that of decamethoxin. It was also shown that decamethoxin had a high disinfecting action on CPOM pathogens. It was noted that decamethoxin had a marked ability to increase the bactericidal action of poviargol (by 2-14 times) and its disinfecting action (by 2 times) on Proteus spp., E. coli and Ps. aeruginosa. PMID- 1304132 TI - [Ciprofloxacin and other antimicrobial drugs in the treatment of disseminated peritonitis]. AB - Forty two patients with general peritonitis were treated with ciprofloxacin and combinations of various antimicrobial drugs. Ciprofloxacin had the highest effect on aerobic and anaerobic microbes in the peritoneal cavity which defined the favourable clinical results in all the patients. Moreover, there were observed no disorders in the composition of the normal intestinal microflora which in the end promoted a decrease in the number of the patients with suppuration of the surgical wound. PMID- 1304135 TI - [Acute myocardial infarction II]. PMID- 1304134 TI - [Effect of antibiotics on the absorption of basic nutrients]. AB - The impact of tetracycline, gentamicin, streptomycin, erythromycin, oxacillin, benzylpenicillin and sulfanilamides on the absorption function of the small intestine was studied in 79 patients with chronic bronchitis. The drugs were shown to mainly inhibit fat absorption: on the average, by 87 per cent in all the patients treated with tetracycline, on the average, by 89 and 36 per cent in 80 70 per cent of the patients treated with gentamicin and streptomycin, respectively, and, on the average by 26 and 16 per cent in 20-25 per cent of the patients treated with erythromycin and oxacillin, respectively. The absorption of protein decreased, on the average, by 23-74 per cent in all the patients treated with tetracycline, gentamicin and streptomycin. As for the other drugs, they had, on the average no significant effect on protein absorption. The absorption of carbohydrates (d-xylose) significantly decreased under the effect of these three drugs (by 21, 34 and 36 per cent, respectively). The analysis revealed a relation of absorption function to the presence and degree of intestinal dysbacteriosis. PMID- 1304136 TI - [How has the prognosis of myocardial infarction changed in the last 30 years?]. PMID- 1304137 TI - [Indications for coronarography and coronary angioplasty during the 1st week after myocardial infarction]. AB - There is little data available on the precise indications of coronary angiography and myocardial revascularisation during the first week after myocardial infarction. Mechanical complications (subacute rupture, ventricular septal defect, ruptured mitral chordae), usually require emergency surgery: when the patient's haemodynamic status permits, preoperative coronary angiography is desirable. Recurrent ischaemia may be treated by urgent coronary angiography- dilatation; nevertheless, the results of this type of procedure are associated with high mortality and morbidity and it would seem better practice to start with repeat intravenous thrombolytic therapy: coronary angiography can then be performed in a less acute situation with a view to angioplasty. Finally, in most cases of uncomplicated infarctions, functional investigations such as exercise stress testing coupled with radioisotopic methods, may be usefully performed before coronary angiography to demonstrate any residual ischaemia justifying a myocardial revascularisation procedure: under these conditions, it seems more realistic to envisage coronary angiography 8 to 10 days after the initial coronary event. PMID- 1304138 TI - [How to and why evaluate the ischemic risk after myocardial infarction?]. AB - After uncomplicated myocardial infarction, clinical and ergometric data before hospital discharge allow identification of patients at high risk of further cardiac events. These relate to the necrosed myocardium (left ventricular dysfunction, sometimes latent, and arrhythmia risk), and also to the jeopardized myocardium: the moderate sensitivity and specificity of classical exercise stress testing for the detection of this often silent ischaemia are much improved by stress radionuclide and echocardiographic techniques (exercise, dipyridamole, dobutamine. . .), the large scale indications of which remain to be validated. PMID- 1304139 TI - [How to evaluate the hemodynamic risk after myocardial infarction?]. AB - The hemodynamic prognosis of myocardial infarction is determined, at medium and long term, by the function of the left ventricle. This is related to the infarct size, the dilatation and geometry of the ventricle secondary to left ventricular remodeling which often follows infarction. In addition to clinical criteria, the hemodynamic parameters which are essential for patient evaluation are the ejection fraction (by radionuclide or conventional ventriculography), rapidly progressive ventricular dilatation (by repeated echocardiography) and circulatory reserve from the exercise stress test data. PMID- 1304140 TI - [How to evaluate the arrhythmogenic risk after myocardial infarction?]. AB - The risk of sudden arrhythmic death after myocardial infarction is high, especially during the first months. The evaluation of this risk should be performed before hospital discharge in the same way as residual ischaemia and left ventricular function, which are independent risk factors for arrhythmia, are assessed. Holter monitoring provides information not only about ventricular hyperexcitability (especially the detection of unsustained ventricular tachycardia) but also about the activity of the autonomic nervous system by analysis of variations of the sinus rhythm, the decrease of which carries a poor prognosis. The search for an arrhythmogenic substrate requires signal averaged electrocardiography, but although the absence of late potentials carries a good prognosis, the positive predictive value of this investigation is very low. The association of non-invasive indices of poor prognosis greatly increases the probability of a major arrhythmic event; this may require consideration of programmed ventricular pacing, another method of substrate and risk assessment, which has the added advantage of sometimes indicating the most appropriate therapy. PMID- 1304142 TI - [Treatment of risk factors of coronary atherosclerosis]. AB - The treatment of coronary atherosclerosis risk factors is an essential part of secondary prevention of myocardial infarction. This should be started during the acute phase. Hypercholesterolemia is the principal causal factor and the occurrence of an infarct does not change the relative cardiovascular risk attributable to this factor. The absolute risk, positively correlated to total and LDL cholesterol and negatively to HDL cholesterol, is increased after myocardial infarction because of the higher prevalence of lethal or non-lethal ischemic cardiac events. The benefits of cholesterol reduction on cardiovascular mortality have been clearly established. They are greater with cholesterol lowering drugs than with diet alone, and all the more significant when the initial cholesterol levels are high, but they are present at every value. A 1% reduction in total cholesterol is associated with a 2.5% reduction in coronary mortality both in secondary and primary prevention. After infarction, the cardiovascular benefits greatly exceed the risk of overmortality from other causes. Therapeutic effects may also be demonstrated by non-progression or regression of stenotic coronary lesions. The benefits of hypertension control are not as evident. Diastolic blood pressures inferior to 85 mmHg are associated with an increased coronary risk. While waiting for the results of specific therapeutic trials, reduction of high blood pressure without excessive lowering of the diastolic pressure is recommended. Stopping smoking is a measure of primary prevention which reduces the number of acute coronary events and of sudden deaths. However, the correlation with atherosclerosis is not remarkable. Treating diabetes, sedentarity and psychological behaviour seems to be useful. An evaluation of a personalized multifactorial approach to individual risk should be performed. PMID- 1304141 TI - [Rehabilitation centers: for whom? Why and how long?]. AB - The clinical profile of coronary patients admitted to cardiac rehabilitation centres after myocardial infarction has changed considerably in the last 15 years. Complementary investigations (coronary angiography, studies of left ventricular function) provide accurate information which improves the process of rehabilitation. Global management of the coronary patient requires and justifies, especially in young adults, taking into consideration the physical, psychological and socio-professional consequences of a myocardial infarction. The indications of rehabilitation are much more comprehensive nowadays. Even patients with significant haemodynamic impairment can benefit from a stay in a specialised centre. Contraindications are usually only temporary. Finally, an enquiry performed in 33 French cardiac rehabilitation centres shows large variations in methods, personnel and organisation. However, as a general rule, a 3 week stay seems to be adequate but it is logical to continue rehabilitation when the patients goes home to pursue and maintain at long term the results obtained on discharge from a specialised centre. PMID- 1304143 TI - [Role of antithrombotic agents after myocardial infarction]. AB - Thrombosis is the causal mechanism of myocardial infarction: severe atherosclerotic narrowing, ulceration of the atherosclerotic plaque and disequilibrium between pro and antithrombotic factors, predispose to this complication. Recurrent myocardial infarction is a common complication in the year following an initial event: the risk is higher when the diseased artery has been recanalized in the acute phase. Reocclusion of the recanalized artery without signs of infarction is also a common occurrence. It was therefore logical to have striven over the years to prevent reinfarction and/or rethrombosis after reperfusion. Mechanical methods have not been crowned with resounding success and antithrombotic drugs are the only products associated with real benefits in this prevention. In this article, the authors review the efficacy of aspirin and vitamin K antagonists in the prevention of recurrent myocardial infarction; the data in favour of an efficacy of aspirin in preventing early reinfarction is also analysed; finally, results suggesting a benefit of platelet antiaggregant therapy (Flurbiprofen or aspirin) on the risk of reocclusion after therapeutic recanalisation are also assessed. PMID- 1304144 TI - [Prevention of postinfarction cardiac insufficiency: role of angiotensin converting enzyme inhibitors]. AB - Cardiac failure remains a serious complication of myocardial infarction. In addition to therapeutic interventions to limit the infarct size, it would seem possible to influence the progressive changes in geometry and size of the left ventricle, known as remodeling. Experimental and clinical studies have shown beneficial effects of angiotensin converting enzyme inhibitors and the SAVE trial evaluated the prognostic consequences of this therapy, reporting a significant reduction in mortality after 10 months' treatment. Many questions remain which require further research in this field, mainly concerning the optimal time of introduction the treatment, the importance of the chemical molecule used, the most appropriate dosage and the influence of associated drug therapy. ACE inhibitors are now part of the therapeutic arsenal of myocardial infarction but their prescription should be strictly reserved for the population concerned by these trials, that is to say patients with a recent, extensive infarct with left ventricular dysfunction but without clinical signs of cardiac failure. PMID- 1304146 TI - [Psychological aspects of short-term follow-up in myocardial infarction]. AB - The author analyses the outcome and emotional repercussions of myocardial infarction in the patient, his or her partner, and of the medical team who manages the infarct (coronary care and cardiac rehabilitation). The adaptive value of certain psychological attitudes is emphasised, for example the denial of illness, and the poor prognosis associated not so much with "type A" behaviour reputed to cause coronary disease but more with post-infarction depression or even with a more stable tendency to hostility in the emotional control. Some of these psychological characteristics may explain the difficulties encountered in designing educative programmes or in poor therapeutic observance by patients despite being aware of the risks they run. These considerations led to therapeutic implication ranging from the strategy of communication with the coronary patient to specific relaxation techniques or with help, to the gestion of stress, to the judicious prescription of psychotropic agents. PMID- 1304145 TI - [Myocardial infarction beyond the 48 first hours: treatment with calcium channel antagonists]. AB - Calcium channel blocking agents prevent calcium entering cardiac and smooth muscle cells. With reduction of the blood pressure, heart rate and myocardial contractility, they reduce myocardial oxygen demand. By relieving spasm and coronary constriction, and dilating the collateral coronary vessels, they improve perfusion of the ischemic zones. The results in experimental infarction are contradictory: the reduction in the infarct size and ischaemia is not constant. In the Myocardial Infarction Study, a trial of lidoflazine in 1792 subjects followed up for an average of 5 years, there was no significant difference between the mortality rates of the two groups. In the Danish Verapamil Infarction Trial I, which included 436 subjects receiving 360 mg/day of verapamil or placebo, the 6 months mortality was less (NS) in the verapamil group (12.8%) than in the placebo group (13.9%) as was the reinfarction rate (7.8% versus 9.2%; NS). In the DAVIT II trial of 1775 subjects, treatment was introduced 9 +/- 2.7 days after admission. Mortality was lower (NS) in the verapamil group (11.1%) than in the placebo group (13.8%) and the recurrences were less common (p = 0.04) in the treatment group (11.0%) than with placebo (13.2%). The Secondary Prevention Reinfarction Israeli Nifedipine Trial is a comparison of Nifedipine 30 mg/day and placebo introduced 7-21 days after infarction in 2276 subjects. After 10 months, the mortality and reinfarction rate were similar in both groups, as in the SPRINT II trial (60 mg/day of nifedipine or placebo) at 6 months. In the Multicenter Diltiazem Postinfarction Trial of 2466 patients, Diltiazem 240 mg/day or placebo was administered 3 to 15 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304147 TI - [Return to work after myocardial infarction: evaluation and decision]. AB - Working capacity after myocardial infarction depends on the physical and cardiovascular status, psychological repercussions and conditions of work. The latter two are much more important than the first two factors. Cardiovascular functional status is readily assessed by the large number of available investigations which leave little unknown. Exercise stress testing during the second week is the most cost-efficient investigation, providing reliable and sufficiently quantifiable data about the possible sequellae of cardiac failure on effort, ischemia and arrhythmias: an idea of the patient's functional capacity and circulatory responses (athletic, hyperkinetic) may also be obtained allowing adjustment of treatment to improve exercise capacity which goes much further than the statistical hope of prolonging survival. However, it would be naive to think that a satisfactory exercise stress test guarantees the patients' capacity to return to work. Psychological and sociological factors are more important by far. The dominant trait of the post-infarction psychological syndrome must be identified (anxiety, depression, negation): the positive and negative influences of the family, social and professional environment must be evaluated. A good knowledge of the patient's working conditions is essential to go against a number of taboos hindering the return to work (stress, stairs, restaurant meals, etc...). Finally, the medico-legal relationship between the infarct and work should not be neglected: the management of myocardial infarction when an occupational disease must respect the legislative and judicial texts which do not always correspond with everyday clinical practice. There is a lack of structures for cardiac function testing for assessing physical aptitude: we suggest that in the context of the proposed hospital reforms, departmental heads should consider setting up such units which would have a specific task respecting the spirit of these reforms. Nevertheless, cardiologists should pay more attention to the convalescent phase of infarction. This is the time when many social catastrophes can be avoided. PMID- 1304148 TI - [Effects of technological and socio-cultural developments on the practice of neonatal medicine]. PMID- 1304149 TI - [Blood transfusions and kidney transplantation]. PMID- 1304150 TI - [Adolescents and legislation in health and sexuality matters]. PMID- 1304151 TI - [Immunity to and incidence of measles in a population of Parisian children]. AB - BACKGROUND: Measles remains prevalent in France despite the development of nationwide vaccination program. This study evaluates measles immunity and correlates it with active immunization. MATERIAL AND METHODS: A total of 250 (131 boys and 119 girls) French children, aged 2 to 15 years, seen as outpatients in our hospital, were studied from 1.01.90 to 1.06.91; 133 had received live measles vaccine during the 2nd year of life, the 117 others were not vaccine-protected. Evaluation included medical records, specially those concerning past-history of measles or measles-like diseases and immunizations. Measles IgG and IgM antibodies (ELISA) were looked for in all 250 children. RESULTS: 102 of the 117 children who were not vaccine-protected had a detectable antibody titer. 42 of these 102 had a history of measles, before the age of 5 years in 30, between 5 and 10 years in 9 and after the age of 10 years in 3. Only 4 of the 70 children aged over 10 years and not vaccine-protected had no detectable antibodies. 131 of the 133 actively immunized children had detectable antibodies. CONCLUSIONS: Measles is probably more frequently subclinical than was believed until now. Its relative frequency in France in children who had not received the live vaccine explains the high percentage of those aged over 10 years who had detectable antibodies and the relatively low incidence of the disease in teenagers and young adults. PMID- 1304152 TI - [Enteropathy in premature newborn infants. Prospective study over one year]. AB - BACKGROUND: In neonatal units, there is a tendency to assume that any acutely sick infant with gastro-intestinal symptoms has necrotizing enterocolitis (NEC). This prospective study was conducted to find a better definition of enteropathy in preterm neonates and their risk factors. MATERIAL AND METHODS: All the 351 preterm neonates admitted to a neonatal unit from 1 August 1988 to 31 July 1989 were included in the study. A chart including 45 items was established for each infant, with special attention to data on the pregnancy, delivery, any early ischemic and/or infectious problem, nutrition and any gastro-intestinal (GI) problem. All the neonates were fed similarly, depending their maturation, gestational age and GI status. Each infant was assigned to one of 5 categories: 1) no GI problem; 2) transient obstruction; 3) NEC with pneumatosis; 4) hemorrhagic colitis without obstruction or pneumatosis; 5) other GI disease. RESULTS: 267 infants had no GI problem during their stay in the neonatal unit. 53 developed GI symptoms: 23 transient obstructions, 6 NEC, and 24 hemorrhagic colitis. The mean age at onset of symptoms in these last 3 categories was 7 days, 14 days and 23 days, respectively. Ten risk factors were found to be significantly correlated with GI disturbances: umbilical venous catheter, benzodiazepines, birth weight < 1,500 g, patent ductus arteriosus, ventilatory assistance, abnormal amniotic fluid, gestational age < 32 weeks, early antibiotic treatment, passage of meconium > 48 hours, episodes of apnoea and/or bradycardia. CONCLUSION: This follow-up shows that the GI disturbances of preterm neonates admitted to a neonatal unit, specially those having one or more risk factors, can be separated into 3 groups: 1) isolated intestinal obstruction, seen in the most immature babies during the first week of life with the risk of developing NEC; 2) frank blood in the stool, indicating colitis and possibly minor forms of NEC; 3) combined obstructive and hemorrhagic symptoms, typical of NEC. PMID- 1304153 TI - [Comparison of measurements of cholesterol, glucose and uric acid taken at 5-year intervals in children and adolescents]. AB - BACKGROUND: There are several reports on cardiovascular disease risk factors but, except for lipids and lipoproteins, there have been few studies tracking blood uric acid and glucose in healthy school children. MATERIAL AND METHODS: Blood specimens were collected from 4,299 children and adolescents for determination of cholesterol, uric acid and glucose. The first samples were collected between 1977 and 1979 from subjects aged 4 to 17 years. The second samples were collected 5 years later. RESULTS: The blood glucose concentrations increased before the age of 10 years; those of uric acid increased during the second decade and those of cholesterol decreased during puberty, to a greater degree in boys. Hypercholesterolemia (cholesterol > 5.9 mmol/l) was found in about 6% of boys and 10% of girls. Eight boys and 3 girls had blood glucose concentrations higher than 6.7 mmol/l at the first collection. 5 years later, the correlation coefficients by sex and by cross section of age were greater than 0.5 for cholesterol and uric acid and were about 0.3 for glucose. CONCLUSIONS: Successive blood values of glucose and uric acid are highly correlated; those of cholesterol are more highly correlated. However, the probability of remaining in the same percentile distribution remains below 50% for subjects whose initial values were above the 80th percentile. PMID- 1304154 TI - [Regressive myelodysplastic syndromes in children. Committee on Childhood Myelodysplasia of the Society of Pediatric Hematology and Immunology]. AB - BACKGROUND: As in adults, myelodysplastic syndromes in children are often preleukemic and their spontaneous remission is exceptional. CASE REPORTS: Case 1. A girl, aged 8 years, developed pancytopenia with macrocytic anemia. The myelogram and bone marrow biopsy showed dyserythropoiesis with macroblastosis, but without sideroblasts. The chromosome configuration was normal and the negative results of other investigations led to the diagnosis of refractory anemia without any known cause. Bone marrow transplantation was considered, but a spontaneous remission intervened and has persisted for 3 years. Case 2. A girl, aged 5 years, was investigated for worsening of a macrocytic anemia that had been present for 3 years, without changes of granulocytes and platelets. The myelogram showed dyserythropoiesis with megaloblastosis and sideroblasts. No known cause could be identified. As for the preceding patient, a spontaneous remission occurred, and has persisted for 3 years. Case 3. A girl, aged 5 months, developed pancytopenia. The myelogram showed dys-megakaryocytopoiesis. All hematologic data spontaneously normalized after 1 year, and have remained so 1 year later. CONCLUSION: The spontaneous remission, that has occurred in our 3 patients, has been reported in one only adult. This possibility precludes considering all the myelodysplastic syndrome in children as preleukemic, and suggests that bone marrow transplantation is not urgent in these situations. PMID- 1304155 TI - [Infantile spasms associated with a brain tumor]. AB - BACKGROUND: Infantile spasms are exceptionally associated with a focal cerebral lesion such as a brain tumor. CASE REPORT: A 15 month-old girl was treated with hydrocortisone and valproic acid for infantile spasms that had appeared a few days earlier. Her psychomotor development was considered normal and the CT scan was normal. Clinical symptoms disappeared within 10 days and the EEG became normal except for a few epileptiform discharges in the frontal areas. The girl developed partial seizures at the age of 5 years. Imaging techniques showed a brain tumor in the right frontal lobe. Surgical excision was followed by radiation therapy. Analysis of the tumor showed an astrocytoma. The girl is normal 18 months after intervention. CONCLUSION: It is difficult to determine a relationship between the infantile spasms and the brain tumor in this case. The moderately asymmetrical pattern of the EEG after infantile spasms, the fact that these spasms appeared relatively late and the persistence of discharges, lead to repeated specialized investigations. PMID- 1304156 TI - [Neonatal gastric necrosis]. AB - BACKGROUND: Neonatal necrotizing gastritis is rare. It is usually a complication of acute anoxia or shock and its diagnosis is essentially radiological. CASE REPORTS: Case no. 1: a boy was born at the 36th week of a pregnancy complicated by preeclampsia. Perinatal asphyxia necessitated delivery by cesarean section. He presented with neonatal respiratory distress which was complicated by pneumothorax. On the 5th day of life, the abdomen was distended and the newborn had still not been fed. On the 6th day, X-rays showed pneumatosis of the gastric wall associated with pneumoperitoneum. Surgery showed an area of necrosis on the posterior surface of the stomach with a small perforation, which was stitched. The child was fed 5 days later and was in good condition at the age of 6 months. Case no. 2: a girl was born at the 35th week of a pregnancy complicated by asthma during the second trimester. Perinatal asphyxia and abnormal fetal rhythm led to delivery by cesarean section. At 24 hour of life, she vomited blood and fibroscopy confirmed the presence of blood in the stomach. On the 3rd day, blood vomiting appeared again, associated with abdominal distension. X-rays showed pneumatosis of the gastric wall; fibroscopy showed necrosis of the lower 2/3 of the stomach. Feeding was stopped and the child was given cimetidine. Refeeding was possible when the girl was 10 days old, and she was in good condition at the age of 6 months. CONCLUSION: Neonatal gastric necroses and necrotizing enterocolitis have many similar features. Medical therapy is often effective, but surgery is mandatory when necrotizing gastritis is complicated by perforation. PMID- 1304157 TI - [Antenatal bilateral sylvian infarction and congenital syphilis]. AB - BACKGROUND: The classical symptoms of congenital neurosyphilis include meningovascular lesions that are responsible for CSF abnormalities. Lesions of larger vessels are very unusual. CASE REPORT: A boy was born from a neglected pregnancy, weighing 2.7 kg. He was abandoned by his parents and was admitted to hospital at 40 days of age (weight: 2,220 g; height: 47 cm; head circumference: 22 cm) with axial hypotonia, peripheral spasticity and shock syndrome. The TORCH screen was negative but the Treponema Pallidium Hemagglutination Assay (TPHA) was positive. The infant died 4 days later. Brain pathological studies revealed meningoencephalitis and bilateral sylvian infarction. CONCLUSION: Local arteritis due to syphilis usually concerns small arteries, such as the meningeal and cortical vessels. The occlusion of the two middle cerebral arteries seen in this patient, which were responsible for atrophy of the parietal lobes, is uncommon in congenital syphilis. PMID- 1304158 TI - [Severe form of neonatal hemolytic disease by anti-Vel allo-immunization]. AB - BACKGROUND: Routine detection of maternal sensitization during pregnancy sometimes reveals alloimmunization by exceptional antigens. CASE REPORT: A first pregnancy was complicated by a severe post-partum anemia in the mother, that required a blood transfusion. Irregular agglutinins were detected during the first trimester of a second pregnancy, for which the father was different from the first. The specific antibody was not identified at that time. The newborn, born at a gestational age of 39 weeks, developed severe jaundice at 3 hours of life, with hemolytic disease, anemia and hepatomegaly. Therapy included two transfusions of packed, washed red cells obtained from the mother on days 7 and 25. Immunologic tests showed that the hemolytic disease of this newborn was due to an anti-Vel alloimmunization. CONCLUSION: Antibodies detected during the pregnancy must be identified in order to manage properly any perinatal problems due to rare antibodies. PMID- 1304159 TI - [Cerebral embolism revealing aneurysm of the interauricular septum]. AB - BACKGROUND: Aneurysm of the interatrial septum is a potential cause of systemic embolism, but it is rarely responsible for a cerebral embolism in childhood. CASE REPORT: A girl, aged 14 years, presented with a sudden right hemiplegia. The coagulation factors were normal, as was the CSF. The CT scan was normal and the EEG showed some theta waves (3-4/s) on the left temporal lobe. MRI, performed 6 days later, showed ischemic lesions leading to a search for the origin of the embolism. One-dimensional echocardiography revealed no abnormality, but two dimensional echocardiography showed an aneurysm of the interatrial septum bulging into the right atrium. The child was treated with low doses of acetylsalicylic acid, but still had a moderate degree of spastic hemiplegia one year later. CONCLUSION: Cardiopathies can be among the causes of cerebral embolism in children. An aneurysm of the interatrial septum requires treatment throughout patient's life. PMID- 1304160 TI - [Iconographic rubric. Polyarthritis in congenital syphilis]. PMID- 1304161 TI - [Staphylococcal and streptococcal toxic shock syndromes in children]. PMID- 1304162 TI - [Genetic basis of early aging]. PMID- 1304163 TI - [Pharyngo-laryngeal localization of Crohn disease in a child]. PMID- 1304164 TI - [Extracorporeal respiratory assistance (ECRA) in neonatal intensive care: a good choice?]. PMID- 1304165 TI - [Beware of compounded drugs. Apropos of a case of atropine poisoning]. PMID- 1304166 TI - [Sudden death and lipoma of the corpus callosum]. PMID- 1304167 TI - [Neonatal icterus and erythrocyte glucose-6-phosphate dehydrogenase deficiency in Congolese newborn infants in Brazzaville]. PMID- 1304168 TI - [Marfan syndrome. Current molecular data]. PMID- 1304169 TI - (R)-(-)- and (S)-(+)-adenallene: synthesis, absolute configuration, enantioselectivity of antiretroviral effect, and enzymic deamination. AB - Synthesis of optically pure (-)- and (+)-adenallene 2 and 3 is described. Racemic adenallene (1a) was subjected to deamination with adenosine deaminase monitored by HPLC using a Chiralcel CA-1 column to give (-)-adenallene (2) and (+) hypoxallene (4). The latter compound was converted to acetate 5. The reaction of 5 with trifluoromethanesulfonic anhydride and pyridine followed by ammonolysis furnished acetate 6 or (+)-adenallene (3) depending on the solvent used in the last step. Acetate 5 was smoothly transformed to the 6-chloro derivative 7, but an attempted ammonolysis led only to racemization and decomposition. Single crystal X-ray diffraction established the R-configuration of (-)-enantiomer 2. The latter forms a pseudosymmetric dimer in the lattice with the adenine moiety in an anti-like conformation. The torsional angles of the allenic bonds show departures from 90 degrees (91 and 97 degrees, respectively) and rotameric preference of the hydroxymethyl groups is different in both molecules of the dimer. The R-enantiomer 2 inhibited the replication and cytopathic effect of human immunodeficiency virus (HIV-1) in ATH8 cell culture with an IC50 of 5.8 microM, whereas the S-enantiomer 3 was less active (IC50 > 200 microM). The enantioselectivity of the anti-HIV effect is significantly lower than that of 2',3'-dideoxyadenosine. Kinetics of deamination of R- and S-enantiomers 2 and 3 catalyzed by adenosine deaminase gave the following parameters: Km values of S form 3 and R-form 2 were 0.41 and 0.52 mM with Vmax being 530 and 18.5 mumol/min, respectively [corrected]. Again,, a much lower level of enantioselectivity of deamination was observed than that of D- and L-adenosine. These results indicate (i) different enantioselectivity of enantiomers 2 and 3 as HIV inhibitors and adenosine deaminase substrates and (ii) both R- and S-enantiomers 2 and 3 can function as nucleoside analogues with varied enantioselectivity for different enzymes or receptors. PMID- 1304170 TI - Intra-individual variability of caffeine elimination in healthy subjects. AB - Caffeine is a popular test substance for assessing the activity of hepatic drug metabolizing enzymes in vivo and in vitro. A correct estimation of the relative magnitudes of intra-individual and inter-individual variations in caffeine elimination is significant for the use of the elimination parameter of caffeine to characterize the biotransformation capacity of a specific form of cytochrome P 450 (1AII) in vivo. The purpose of this study is to demonstrate the magnitudes of fluctuation of caffeine-clearance and half-life as well as inter- and intra individual comparison in 12 healthy male subjects. Compared to the high reproducibility of caffeine decay curves in each healthy male, caffeine elimination varied more extensively between subjects. The distribution of variance amounted to: intra-individual 21.4%, inter-individual 78.6%. The knowledge of variance provided precise evidence of the sample size, which is necessary to prove previously defined differences. PMID- 1304171 TI - FEV1 and peak flow: Wright and the mini meters. PMID- 1304172 TI - Superior oblique tuck surgery in the management of superior oblique palsies. AB - Three hundred and twenty-four patients with superior oblique muscle palsies required surgery over a 15-year period. Forty-four patients underwent superior oblique tuck surgery. Fifteen patients had unilateral and six bilateral tucks alone. Seventeen had unilateral tucks and three bilateral tucks in conjunction with other extraocular muscle surgery. Three had unilateral tucks with a contralateral Harada-Ito procedure. The best results were obtained with isolated superior oblique tucks and tucks in conjunction with a contralateral inferior rectus muscle recession or an ipsilateral inferior oblique muscle weakening procedure. The mean vertical correction following isolated, unilateral surgery was 3.6 prism diopters (range, 0 to 11 delta) in primary gaze and 15.3 delta (range, 0 to 40 delta) in the field of maximum deviation. The mean eso correction in downgaze with bilateral superior oblique tucks was 15.2 delta (range, 10 to 21 delta). There was no statistically significant correlation between the size of the tuck and the amount of deviation corrected. Some degree of postoperative Brown syndrome was seen in all patients, but became less marked with time and in no patient was it severe enough to require reversal of the tuck. In only four patients was there a significant lessening of the effect of the procedure with time. The results show that the superior oblique tuck procedure is an effective operation. In patients with unilateral muscle palsies, 64.3% with an abnormal head posture, 37.5% with diplopia, and 100% with both an abnormal head posture and diplopia achieved an excellent result. In patients with bilateral muscle palsies, 50% with an abnormal head posture and 66% with both an abnormal head posture and diplopia achieved an excellent result. PMID- 1304173 TI - High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. AB - We have previously identified, in three British families having an index child with frequent infections, a point mutation (GGC-->GAC) in codon 54 of exon 1 of the gene for the human lectin mannose binding protein (MBP). This was associated with low serum levels of this complement activating protein and would be anticipated to impair opsonization of mannose rich microorganisms. We now report a second point mutation (GGA-->GAA) in Gambians from West Africa, involving codon 57 of exon 1. By substituting carboxylic acids for axial glycines in the translated proteins both mutations would be expected to disrupt the secondary structure of the collagenous triple helix of the 96 kDa MBP subunits. In the Gambians the codon 57 mutation was studied by PCR, sequence analysis and restriction analysis and found to be remarkably common (frequency of the mutant gene 0.29 in adults and 0.23 in newborns) whereas the codon 54 mutation was very rare (frequency 0.003). However, the codon 54 mutation was frequent in both a British Caucasian and a Hong Kong Chinese population (frequency of the mutant gene 0.17 and 0.11 respectively). It was predicted that both homozygous and heterozygous individuals would have profoundly reduced serum levels of the protein and this was confirmed by immunoassay as was the reduced capacity of such sera to activate complement through the MBP initiated classical pathway. Our data indicate that the two mutations have arisen independently since the divergence of African and non African populations and both have attained high frequencies. PMID- 1304174 TI - Microleakage of amalgam restorations using Amalgambond and Copalite. AB - This study compared the effect of using either Amalgambond as a cavity liner or Copalite in the reduction of microleakage in amalgam Class V restorations. Both retentive traditional and non-retentive cavity preparations were compared with gingival cavosurface margin locations both in enamel and in dentin. Cavity preparations were restored with their appropriate liner, thermocycled, and stored in erythrosin red stain for 10 days. The samples were then sectioned and degrees of microleakage determined. Statistical interpretation with the Wilcoxon test showed that microleakage was significantly greater (alpha = 0.05) with the non traditional cavity design and with cavity margins located in dentin. The results also showed that Amalgambond as a cavity liner significantly reduced microleakage when compared to Copalite. PMID- 1304175 TI - Effect of a fluoride solution on dentinal hypersensitivity. AB - This two-phase experiment assessed the effects over time of a solution containing 1.09% sodium fluoride, .40% stannous fluoride, and .14% hydrogen fluoride (.717% fluoride solution, DentinBloc) on pain associated with dentinal hypersensitivity. During phase I, 30 subjects demonstrating dentinal hypersensitivity to a blast of cool air were divided into three double blind experimental groups. After baseline data were collected for all subjects, one group was instructed to apply the .717% fluoride solution twice a day. A second group was instructed to apply a gel containing .04% stannous fluoride (Gel-Kam) twice a day. A third group was instructed to apply distilled water. Each subject was assessed at 2, 4, 8, and 16 weeks utilizing the "method of limits" with a standardized, repeatable cold thermal stimulus. The results of a two factor repeated ANOVA indicated that those subjects who applied the .717% fluoride solution reported significantly less sensitivity at the 2-week period than the other groups (P < .05). In addition, those subjects whose solution contained the 0.4% stannous fluoride reported significantly less sensitivity at the 4- to 8-week periods (P < .05). Phase II of the study assessed the .717% fluoride solution on a more precise time course. These included: immediately, 15 minute, 1 day, 1 week and 2 weeks. A one factor repeated ANOVA revealed that this effect presented 15-minute post application (P < .05) and continued throughout the testing periods. It was concluded that the fully active 0.717% fluoride solution was an effective agent in the control of dentinal hypersensitivity after two 1-minute applications. PMID- 1304176 TI - Clinical effectiveness of a dentifrice containing potassium chloride as a desensitizing agent. AB - Sensodyne F, a dentifrice currently marketed in the United Kingdom, containing potassium chloride (KCl) and sodium monofluorophosphate (MFP) was compared to a placebo dentifrice for effectiveness in alleviating dentinal hypersensitivity. This randomized, double-blind, parallel clinical study covered 12 weeks of product use by 41 subjects. Hypersensitivity levels of the affected teeth were assessed by tactile stimulation, cold air stimulation and overall subjective patient response. The results from these three methods of assessment demonstrated that the KCl/MFP dentifrice was significantly more effective than the placebo dentifrice in reducing dentinal hypersensitivity. The therapeutic response to the KCl/MFP dentifrice as measured by air sensitivity and overall subjective evaluation was statistically significant when compared to the placebo dentifrice within 4 weeks of use. Significant improvement was observed for all parameters at the conclusion of the 12-week clinical study period. Plaque reduction was significantly reduced at week 8 and continued to improve by week 12. The results indicate that KCl with sodium MFP significantly reduced dentinal hypersensitivity and improved overall patient comfort. PMID- 1304177 TI - Effect upon plaque formation and gingivitis of a triclosan/copolymer/fluoride dentifrice: a 6-month clinical study. AB - A total of 159 adult male and female subjects between 18 and 63 years of age, were entered into a 6-month, double-blind clinical study to assess the effects of a dentifrice containing 0.3% triclosan and 2% of a copolymer of methoxyethylene and maleic acid on supragingival plaque formation and gingivitis, as compared to a placebo dentifrice. Both the triclosan and placebo dentifrices contained 0.243% sodium fluoride in a silica base. The subjects had to demonstrate at least mild gingivitis (modified Loe-Silness score > or = 1.0), be free of advanced periodontal disease, have a modified Quigley-Hein Plaque Index score of at least 1.5 and have a minimum of 20 natural, uncrowned teeth. The subjects were stratified into two balanced groups according to baseline plaque and gingivitis scores. At zero time or baseline, all subjects received a complete and thorough oral prophylaxis and were assigned to the use of either the placebo dentifrice or the triclosan/copolymer dentifrice for the next 6 months. Subjects were evaluated for gingivitis and supragingival plaque formation after 3 and 6 months product use. After 3 months, when compared to the placebo dentifrice, the triclosan/copolymer dentifrice provided the following statistically significant reductions (at 99% confidence levels): (1) a 10.0% reduction in supragingival plaque formation; (2) a 20.8% reduction in plaque formation on tooth surfaces with highest baseline plaque scores; (3) a 21.9% reduction in gingivitis, and (4) 30.5% less sites with severe gingivitis, i.e. gingival bleeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304178 TI - Triclosan/copolymer/NAF dentifrice prophylaxis, reduced etching time and shear bond strength of a resin composite to enamel. AB - This study evaluated the effect of a prophylaxis with a triclosan/copolymer/NaF dentifrice (Colgate Gum Protection Formula) and a reduced etching time with 37% phosphoric acid gel on the shear bond strength of a resin composite to enamel. 60 human extracted permanent molars were used. A flat enamel surface was obtained with 600 grit SiC paper and cleaned with a rubber cup and a water slurry of fine flour of pumice. The teeth were randomly distributed into 4 groups of 15 teeth each: Group 1: Pumice prophylaxis with a rubber cup, etched for 30 seconds; Group 2: Pumice prophylaxis, etched for 60 seconds; Group 3: Triclosan/copolymer/NaF dentifrice prophylaxis, etched for 30 seconds; Group 4: Triclosan/copolymer/NaF dentifrice prophylaxis, etched for 60 seconds. After etching, rinsing and drying, an unfilled resin (Coe Bond) was thinly applied with a brush and cured for 30 seconds. A nylon ring was placed over the area and filled with a light-cured resin composite (Occlusin). The teeth were thermocycled for 500 cycles and sheared with a knife-edged blade in an Instron running at a crosshead speed of 1 mm/min. The results in MPa were as follows: Group 1: 18.84 +/- 7.08; Group 2: 22.65 +/- 4.37; Group 3: 18.79 +/- 5.77; Group 4: 19.62 +/- 6.13. An ANOVA showed that there was no statistically significant difference among the groups. Enamel fracture occurred in 20% (3/15) in Group 1, 53% (8/15) in Group 2, 20% (3/15) in Group 3, and 47% (7/15) in Group 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304179 TI - Interfacial morphology of resin composite and shiny erosion lesions. AB - Ten shiny erosion lesions were divided horizontally, in vivo such that the gingival half was prepared and the incisal half remained unprepared. Both were etched simultaneously with 32% H3PO4 for 20 seconds, rinsed and restored using the All Bond wet technique and P50 composite. The teeth, which were extracted as part of a treatment plan, were sectioned vertically midway through the restorations. Polyvinyl siloxane impressions of the tooth/resin interface were taken and examined by SEM for the presence of gaps. The teeth were then demineralized and the fitting surfaces of the restorations were examined for resin penetration into the dentin. Results showed that there were no gaps present in any of the interfaces. The most proliferative and deep resin penetration occurred in the prepared/etched halves. PMID- 1304180 TI - Bond strengths of Scotchbond Multi-Purpose to moist dentin and enamel. AB - This in vitro study tested the shear bond strengths of the Scotchbond Multi Purpose adhesive system to moist and dry enamel and dentin. After the tooth was etched, the surface was either dried with compressed air or blotted with tissue paper, leaving the surface visibly moist. Primer and adhesive were applied according to the manufacturer's directions. Resin composite posts were applied, and the specimens were thermocycled. Shear bond strengths were determined using an Instron universal testing machine. For both enamel and dentin, mean shear bond strengths were higher when the surface was left visibly moist after etching. Bond strengths to moist and dry dentin were 21.8 and 17.8 MPa, respectively. Enamel bond strengths were slightly lower, with values of 17.0 and 14.2 MPa to moist and dry enamel, respectively. PMID- 1304181 TI - Effect of matrix systems and polymerization techniques on microleakage of Class II resin composite restorations. AB - This study investigated the effect of different sized light curing tips (2 mm and 11 mm) with curing techniques associated with different matrix systems (Mylar with reflective wedge and metal with wooden wedge) on microleakage of a posterior resin composite material (P-50) placed using a bonding agent (Scotchbond 2). Eighty Class II mesial and distal slot preparations (40 with enamel gingival margins and 40 with dentin gingival margins) were randomly divided into four equal groups: 1) metal matrix, large tip; 2) Mylar matrix, light emitting wedge, large tip; 3) Mylar matrix, light emitting wedge, small tip; 4) metal matrix, small tip. Three-way ANOVA indicated no statistical differences among groups using small and large curing tips. The results showed significantly more leakage (alpha = 0.05) in the dentin gingival cavosurface margin groups than the enamel cavosurface margin groups. The results also showed significantly greater leakage in the polymerization procedures associated with the metal matrix groups (alpha = 0.05) compared to polymerization procedures associated with the Mylar matrix groups. PMID- 1304182 TI - Effects of aluminum oxalate/glycine pretreatment solutions on dentin permeability. AB - Aluminum oxalate buffered with glycine to pH 0.5-2.5 has been proposed as a dentin pretreatment for the Gluma bonding system. In this experiment, the effects of 1-minute treatments of smear layers with these aluminum oxalates on the permeability of human dentin were determined in vitro. The aluminum oxalate solutions at pH 0.5-1.5 removed most of the original smear layer but occluded the tubules with crystalline deposits which decreased dentin permeability. Those solutions used at pH 2.0 and 2.5 increased dentin permeability. All dentin pretreatments increased dentin permeability when measured after a 24-hour storage period, especially the solutions at pH 2.0 and 2.5. The SEM correlates of these permeability changes indicated that these solutions remove the smear layer but reocclude the tubules with precipitates which are probably different forms of calcium oxalate, aluminum phosphate and calcium phosphates. PMID- 1304183 TI - Caries-like lesion formation around fluoride-releasing sealant and glass ionomer. AB - Caries-like lesion formation around Class V preparations restored with fluoride releasing sealant, glass ionomer and conventional sealant materials was evaluated with polarized light microscopy following lesion initiation and progression periods. Significant differences (P < 0.05) were found among the three treatment groups for mean surface lesion depth following lesion initiation and progression and between the conventional sealant and fluoride-containing material groups for incremental increase in surface lesion depth following lesion progression. Surface lesion depths were significantly reduced in both the fluoride-releasing sealant and glass ionomer groups when compared with the conventional sealant group. The glass ionomer material provided the greatest degree of caries protection at the enamel-restorative interface and had the least number of wall lesions (7.5%); in contrast, the conventional sealant group had the greatest number of wall lesions (17.5%). The incorporation of fluoride from a dental material into adjacent tooth structure may provide enhanced resistance to caries initiation and progression. PMID- 1304184 TI - Chronic osteomyelitis of the mandible: case report. AB - Chronic osteomyelitis is a devastating disease of unknown etiology. The primary cause is usually thought to be microbiological. The diagnosis of osteomyelitis of the mandible is arduous, particularly in the early stages, and this disease is almost always difficult to cure. Clinical symptoms, radiographic changes and histologic findings are characteristic of this disease. Treatment modalities have been directed toward eradicating microbes and improving circulation, in the early stages. In the case presented, surgical debridement and IV antibiotics were the treatment of choice. The bone biopsy histopathology report in this case, revealed normal bone, which was inconsistent with chronic osteomyelitis. This article delves into the literature providing history and current research trends in the diagnosis, treatment and follow up care for chronic osteomyelitis. PMID- 1304185 TI - Torus palatinus: report of a case. PMID- 1304187 TI - Prolactin and dopamine concentrations in the cerebrospinal fluid during the neonatal period. AB - Prolactin (PRL) has been detected in the cerebrospinal fluid (CSF) in humans and the absolute level appears to reflect the serum PRL concentration. Because PRL is thought to be involved in the regulation of brain water and electrolyte content attempt has been made to determine CSF and plasma PRL and dopamine (DA) concentrations, osmolality, and sodium level in 21 newborn infants undergoing lumbar punction because of apneic spells, fever, or perinatal asphyxia. The mean of gestational age was 36.5 weeks (range: 31-41) and birthweight was 2572 g (range: 1140-3550). The lumbar puncture was performed at the 8.3 postnatal day (range: 1-38). The plasma concentration of PRL was 106.52 +/- 14.43 ng/ml, significantly higher than the CSF PRL level (43.24 +/- 7.39 ng/ml, p < 0.01). This elevated level was observed in all individual cases. DA concentration in the plasma was much higher than the value detected in the CSF (64.75 +/- 13.83 vs 8.64 +/- 0.72 ng/ml, p < 0.01). No difference was observed between the sodium content of the CSF and plasma (138.94 +/- 1.28 vs 138.04 +/- 1.03 mmol/l), however, the osmolality of the plasma tended to be higher than the CSF osmolality (286.7 +/- 3.81 vs 276.76 +/- 2.19 mosm/kg, p < 0.05). In the CSF osmolality, PRL, DA, and sodium concentrations did not show any correlation. IN CONCLUSION: in the CSF PRL probably does not play a primary role in controlling the osmolality and sodium content. PRL in CSF seems to be independent from CSF DA concentration. PMID- 1304186 TI - Electrolyte and glucose concentration in plasma and cerebrospinal fluid measured parallel in pathologic newborn infants. AB - Cerebrospinal fluid and plasma sodium, potassium, chloride, calcium and glucose concentration were measured parallel in 14 pathological newborn babies of gestational age and birthweight of 36.3 +/- 4.3 wks and 2410 +/- 890 g, respectively, at the age of 37.8 +/- 4.4 wks postconceptionally. Whilst potassium, calcium and glucose level is much lower in the cerebrospinal fluid than in the plasma, similar sodium and higher chloride concentration was found in the cerebrospinal fluid. The significant positive correlation between plasma and cerebrospinal fluid glucose and sodium levels proves the lack of a functioning barrier for these compounds. On the other hand, cerebrospinal potassium level varied within a narrow range, independently of the plasma-concentration and the maturity of the studied babies. Pathophysiological implications of the results are further discussed in short. PMID- 1304188 TI - The distribution of lymphocyte subpopulations in an infant with primary intestinal lymphangiectasia. AB - Authors analysed in an infant with primary intestinal lymphangiectasia the number of intraepithelial lymphocytes and the distribution of T lymphocyte subpopulations in the jejunal mucosa with immunohistochemical methods. It was established that the number of intraepithelial lymphocytes and of the cells belonging to the various T lymphocytes markedly decreased in the patient compared to controls, however the decrease of the CD4 cells was less than that of CD8 cells, thus the CD4/CD8 ratio increased. Authors conclude that the increase of CD4/CD8 ratio in the jejunal mucosa may explain the absence of frequent gut infections in intestinal lymphangiectasia. PMID- 1304189 TI - Serotonin concentration in offspring of parents suffering from premature coronary arterial disease. AB - Thirty-one 3 to 14 years old offspring of parents who had an acute myocardial infarction before age of 45 and 42 healthy children without any family history of cardiovascular disease were investigated. A significant increase in plasma free serotonin concentration was seen in endangered children. From these results it may be supposed that vascular endothelium is dysfunctional in offspring of parents suffering from premature coronary arterial disease. PMID- 1304190 TI - Insulin resistance in obese boys with acanthosis nigricans. AB - Insulin resistance was investigated in three obese boys with acanthosis nigricans and their results were compared to those obtained in non-acanthotic obese patients. Blood glucose immune reactive serum insulin and C-peptide during oral glucose tolerance test and 125I-insulin binding investigated. Obese patients with acanthosis nigricans were more insulin resistant than simple obese controls. Insulin binding studies performed in two acanthotic patients suggested that one of them had insulin resistance type A, and the second patient had insulin resistance type B. According to the results acanthosis nigricans can serve as a marker for severe insulin resistance in obesity. PMID- 1304191 TI - The use of human recombinant erythropoietin in children on chronic dialysis. AB - Human recombinant erythropoietin (r-HuEPO, EprexR) was administered to 8 children with chronic renal failure and high transfusion requirement. The hormone was given i.v. 2-3 times per week at the end of the dialysis. The selected initial dose (160 U/kg/week) was gradually raised up to a maximum of 400 U/kg/week. Anaemia normalised by the tenth week. The aimed target haematocrit was 0.33, the average maintenance dose was 250-300 U/kg/week. The absolute reticulocyte count seemed to be a more sensitive indicator of the actual erythropoietin effect than the haematocrit level. No major adverse effects (convulsion, progressive hypertension, thrombosis) were observed during treatment with r-HuEPO. The need for transfusions decreased dramatically, no transfusion was needed following the second week of treatment. The general condition improved substantially. In one hyperimmunized child the cytotoxic antibody titer decreased by 75 per cent. PMID- 1304192 TI - A behavioural teratologic study on offspring of self-poisoned pregnant women. AB - Ninety-three cases born from women who attempted suicide by taking large doses of chemicals and eight cases who had mothers affected by a chemical poisoning as accident during pregnancy were studied. Data of birth weight and gestational time, congenital anomalies and postnatal disorders were obtained in cases and matched controls (sociological twins). Test examinations were performed in both cases--controls and their mothers in the home of families. The mothers of index children had a lower socioeconomic status and more were unmarried than the Hungarian pregnant population at large. The behaviour of index and control mothers showed some obvious differences. The bivariate analyses indicated some possible teratogenic effect of maternal poisoning, but it was not confirmed by multivariate analysis except lower birth weight. Thus differences between cases and control were explained mainly by the maternal behavioural factors. PMID- 1304193 TI - Ewing's sarcoma in the occipital bone. Case report. AB - The head is a very rare primary site for Ewing's sarcoma which occurs most often in the long bones of the extremities and in the pelvis. This report describes an unusual case of Ewing's sarcoma arising from the occipital bone in a seven year old girl. The tumour compressed the venous sinuses, thus lowering the intracranial pressure resulted in temporary recovery which made the diagnosis difficult. PMID- 1304194 TI - [Anisocoria and disordered light reaction]. PMID- 1304195 TI - [Aspects of physiology, pathology and epidemiology of cataract]. AB - World Health Organization estimates that 23 million people have a visual acuity of 0.05 or less. For 12-15 million people cataract is the cause of poor visual acuity or blindness and the majority of those afflicted live in Third World countries. It is estimated that in the year 2025 around 40 million people will become blind due to cataract. The therapeutic procedure of choice is surgical removal of the lens. The high success rate of this procedure in highly industrialized countries has been achieved by the constant improvement in technology and operative technique. This, however, does not hold true for Third World countries. The etiology and pathogenesis of cataract are not yet completely understood. This paper reports on the clinical findings and epidemiology of cataract and deals with the physiology and pathology of the lens. The aim of the study was to recognize possible cataractogenic risk factors. A decrease in the blindness rate caused by cataract in Third World countries can best be achieved through prevention. PMID- 1304196 TI - [Reposition and suture fixation of dislocated posterior chamber lenses]. AB - We treated 11 patients with posterior chamber intraocular lenses that were dislocated into the vitreous cavity. Using a pars plana approach, vitrectomy was performed and in order to facilitate manipulation, half of the bulbus volume was filled by perfluorodecaline. The IOL was grasped with forceps and repositioned with a special technique. In this way the first haptic is fixed in the ciliary sulcus. Fixation of the second haptic with 9 x 0 polypropylene suture was performed with a similar procedure. Finally, prophylactic cryotherapy of the retina is indicated. PMID- 1304197 TI - [Elasticity of capsulorhexis in the animal model]. AB - A special caliper was designed to determine the stretching capacity of a circular capsulorhexis allowing measurements in 0.02 mm increments. A small capsulorhexis 4.5-6.0 mm in diameter could be stretched 2.7 times; a large capsulorhexis 6.5 8.0 mm in diameter was stretched 2.6 times the original diameter. A smooth circular capsulorhexis is very strong and stabile but also has significant stretching capacity. In a small capsulorhexis, there is the danger that zonular fiber defects or posterior capsular rupture may occur during manual expression, of the nucleus. A large capsulorhexis is more suitable for manual nucleus delivery. PMID- 1304198 TI - [Intraoperative complications in cataract surgery. A prospective study]. AB - In a prospective study the important intraoperative complications encountered by two experienced and eight less experienced surgeons after 1708 cataract operations were analyzed. In 2.3% a lesion of the iris or iris sphincter occurred. The overall incidence of capsular ruptures was 0.94%. Zonular dialysis was found in 0.67%. If a severe intraoperative complication with a large capsular or zonular rupture is defined by the necessity for an anterior vitrectomy or the impossibility of implanting a standard posterior chamber lens, the rate of complications was about 0.4%. For the two experienced surgeons, only two anterior chamber lenses as stand-by lens were implanted out of 1500 operations. PMID- 1304199 TI - [In vivo autofluorescence. Measurements of human crystalline lenses with cataract and normal findings after excitation with monochromatic light]. AB - In 25 eyes with nuclear cataract, 18 eyes with posterior subcapsular cataract, 25 eyes with cortical cataract, and 23 eyes without any pathological lens changes, the maximal fluorescence intensity was determined after excitation with monochromatic light at 365 nm, 405 nm, 436 nm, and 485 nm. The coefficient of variation was smaller than 5%. All eyes with cataract underwent cataract surgery a few days after the fluorescence measurements. The fluorescence spectrometer, especially constructed for in vivo measurements, consists of a modified slit lamp (Zeiss 75 SL) and an optical multichannel analyser (OMA) for gauging the data. The clinical trial was undertaken to determine whether, considering the influence of age, there is a difference between the fluorescence intensities in eyes with the above named cataracts and noncataractous eyes. The data were analyzed to determine the effect of age upon fluorescence intensity for all excitation wavelengths in both cataractous and noncataractous eyes. Age had an influence on the fluorescence intensities for all four excitation wavelengths. Assuming that the influence of age was not dependent on the state of the lens, it was quantified for all measurements and an "age-corrected" fluorescence intensity was calculated. The statistical analyses of these "age-corrected" fluorescence intensities revealed a significant difference (P < 0.001) for all of the types of cataracts examined and for normal eyes. The cataract types examined and the normal eyes showed differences in their fluorescence feature. To assess the fluorescence intensities obtained after excitation with the wavelengths mentioned above, one must take into consideration the influence of age on the measurements. PMID- 1304200 TI - [Plasma formation in Nd:YAG laser surgery]. AB - Plasma formation with nanosecond and picosecond Nd:YAG laser pulses was investigated as a function of laser pulse energy to find possibilities for a spatial reduction of the laser effects. The threshold for plasma formation (optical breakdown) in distilled water is 200 microJ for ns pulses and 15 microJ for ps pulses. At a pulse energy of 1 mJ, the plasma length is 80 microns for ns pulses and 250 microns for ps pulses. For the same pulse energy, ps plasmas are on average three times larger than ns plasmas. The plasma length is approximately proportional to the cube root of the laser pulse energy for both ns and ps laser pulses. The decrease in the breakdown threshold achieved by using ps pulses renders photodisruption with a smaller pulse energy (in the microJ range) possible, and therefore a reduction in the side effects. The results are compared with the "moving breakdown" model. PMID- 1304201 TI - [Transscleral posterior chamber lens fixation. Simplified and time saving technique]. AB - Transscleral suture fixation of posterior chamber lenses is preferred to angle supported anterior chamber lenses in cases of complicated cataract surgery with loss of the capsule. One of the disadvantages of suture fixation is the time needed to fix the suture to the haptic of the intraocular lens and to the sclera. Up to now it has been necessary for sutures to be tied separately to the haptic of the posterior chamber lens. With a modified one-piece PMMA posterior chamber lens, which has positioning holes at the vertex of the haptic (Morcher G 48), this is no longer necessary. Using a loop technique, it is possible for a specially designed single-arm loop suture (Ethicon X900G/STC-6) to be fixed safely to this new lens without any knots. Fixation of the sutures can thus be performed more easily and quickly, and there is no more danger of the suture slipping off the haptic. For the first time it has become possible to fix the sutures to the haptic without putting the intraocular lens down in the perioperative field. Reducing the manipulation time on the intraocular lens may also reduce the risk of intraoperative contamination. PMID- 1304202 TI - [Surgical aspiration of secondary cataract. Success quotas and complications]. AB - Cataracta secundaria ("Elschnig pearls") following extracapsular cataract extraction with IOL implantation can be treated by Neodymium-YAG laser capsulotomy or by surgical peeling. The major benefit of the peeling technique is the preservation of an intact posterior capsule. We retrospectively reviewed the peeling procedures (n = 224, mean age: 67 years) performed in our hospital from 1987 to 1990. The results were as follows: (1) In almost all cases (214/224) visual acuity was improved by the operation (mean improvement 0.16-->0.54); (2) major complications were: rupture of the posterior capsule in 9% (20 eyes), mostly (11 cases = 5%) associated with vitreous prolapse; retinal detachment in 1% (2 cases, one with, one without preceding rupture of the posterior capsule); persistnt corneal edema caused by endothelial decompensation in 1 case; (3) recurrence of cataracta secundaria after the first peeling was observed in 26%. Surgical peeling of cataracta secundaria improves visual acuity to about the same extent as Neodymium-YAG laser capsulotomy. It is not without risk, however, and complications occur, including retinal detachment. The possibility that a secondary cataract can reform must be taken into account. PMID- 1304203 TI - [Clinical aspects, follow-up and results of cataract extraction in uveitis]. AB - Over a 5-year period, a consecutive series of 52 eyes in 46 patients with uveitis underwent extracapsular cataract extraction. Twenty-eight of these cases received a posterior chamber intraocular lens (IOL). During an average follow-up of 25 months (range 7 to 58 months) 71% of eyes receiving an IOL achieved postoperatively a visual acuity of 0.5 or better; 54% of aphakic eyes reached this level. Persistent cystoid macular edema limited the visual improvement to 20/200 in 6 patients; none of the patients developed cystoid macular edema postoperatively on clinical observation. Intraocular hypertension occurred postoperatively in 12 eyes, but was limited to a 4-week postoperative period in 9 cases. YAG laser capsulotomy was performed in 2 eyes with opacification of the posterior lens capsule without any further complications. The results suggest that uveitis patients benefit from cataract extraction and in selected cases can tolerate IOL implantation without major complications. PMID- 1304204 TI - [Comparison of various capsulectomy techniques in cataract surgery. An experimental study]. AB - Radial tears at the edge of an anterior capsulectomy are often associated with the occurrence of intraocular lens (IOL) loops coming out of the capsular bag with subsequent IOL decentration. We analyzed the incidence of radial tear formation in 40 human eyes obtained postmortem. These eyes were randomly assigned to four groups: "can opener," linear capsulotomy, capsulopuncture ("postage stamp"), and continuous curvilinear capsulorhexis (CCC). The CCC appeared to be much less likely to be associated with anterior capsular radial tears as opposed to the other three techniques. With the nucleus expression technique used in this study, radial tears occurred in all cases of "can opener," linear capsulotomy and capsulopuncture, whereas no tears occurred with the CCC technique. The results of this study show that CCC is currently the best available anterior capsulectomy procedure for minimizing the incidence of radial tears and sequelae such as decentration. PMID- 1304205 TI - [Early postoperative corneal astigmatism. Comparison of various suture techniques]. AB - We compared two suture techniques after phacoemulsification and implantation of a standard PMMA posterior chamber lens with a 7 mm intrascleral lamellar incision: the cross-stitch (double running) suture closure and the one-stitch technique. Two series with 100 patients each were examined. In the early postoperative period the astigmatism induced was 1.9 +/- 1.4 D in the cross-stitch group and 1.5 +/- 1.0 in the one-stitch group (P = 0.01). In the latter group, 20% more of the patients were found to have a moderate amount of astigmatism. Four weeks after surgery, however, there were no differences between the two groups. The induced astigmatism in both groups was 1.0 D. PMID- 1304206 TI - [Endothelial cell protective effect of high viscosity substances in cataract surgery]. AB - An experimental setting is presented to evaluate the endothelial protection offered by various viscoelastic materials applied in cataract surgery. The substances used were: hydroxypropylmethylcellulosis, a hyaluronic acid preparation (molecular weight 5.10(6), concentration 10 mg/ml), a hyaluronic acid preparation (molecular weight 800 000, concentration: 35 mg/ml), and balanced salt solution as control. The endothelial surface of pig corneas were covered by test substances and spread with a loop of prolene 4.0 suture material in a mechanically standard way. A total of 40 corneas were examined and the amount of endothelial damage evaluated by photometry using Janus-green wash-out, a substance, which selectively binds to damaged endothelial cells or descement membrane. The damaged surfaces differed significantly in all groups of viscoelastic substances and in the control group. Examination showed that the least damage was in group 3, followed by group 1 and the most damage in group 2. Endothelial protection during cataract surgery can be improved by modifications of the substances presently applied. PMID- 1304207 TI - [Ascorbic acid. Cytotoxic effect on cultivated bovine lens epithelium cells]. AB - Ascorbic acid is one of the main components (1.16 mM/l) of the aqueous humor. The molarity of this molecule is 25 times higher than in the plasma of the cow, man or horse. Now the question arises as to which function ascorbic acid has in this extremely high concentration referring to the proliferation of the lens epithelial cells. Thus, the effect of ascorbic acid was investigated upon bovine lens epithelial cells (BLEC) in the range of 0-3 mM/l. These cells were cultivated under various culture conditions (serum-free, serum-containing, aqueous-humor-containing medium) and also incubated with such mitogens as retinal extract (RE), crude endothelial cell growth factor (cECGF), basic fibroblast growth factor (bFGF) or with calcium. In each culture condition 1 mM/l ascorbic acid caused remarkable inhibition of the proliferation of BLEC. Higher concentrations (> 1.5 mM/l) revealed cytotoxic effects. These effects were independent of small variations in the pH value caused by ascorbic acid. In addition, the effect of 2 mM/l ascorbic acid in combination with catalase in a concentration of 500 Um/ml and 1000 Um/ml, respectively, was investigated. It could be shown that catalase is capable of preventing the cytotoxic effect of ascorbic acid. These results show the inhibitory effect of ascorbic acid in its physiological concentration in the proliferation of BLEC. PMID- 1304208 TI - [Effect of heparin on proliferation of cultivated bovine lens epithelial cells]. AB - The treatments proposed to date for the prevention of secondary cataract have shown limited efficacy or have not been satisfactory due to ocular toxicity. Since it has been demonstrated that heparin can inhibit the proliferative activity of smooth muscle cells and fibroblasts in vitro and in vivo, we examined the effect of heparin at concentrations ranging from 20 to 200 micrograms/ml on the proliferation of cultured bovine lens epithelial cells (BLEC) under various culture conditions: (1) serum-free medium (SFM); (2) SFM + aqueous humor 1:1; (3) SFM +1 and 10% fetal calf serum; (4) SFM +1% retinal extract; (5) SFM +50 micrograms/ml endothelial cell growth factor; (6) SFM +10 ng/ml epidermal growth factor; (7) SFM +10 ng/ml basic fibroblast growth factor. Heparin caused no cytotoxic effects in any of the experiments. With medium 2 and 3, heparin caused dose-dependent inhibition of cell proliferation at concentrations ranging from 10 to 50 micrograms/ml. Cells cultivated in medium 4-7 with the addition of 50 micrograms/ml heparin revealed increased proliferative activity when compared with the corresponding controls. The antiproliferative activity on BLEC in medium containing aqueous humor suggests that heparin is a valuable tool for the prevention of secondary cataract in vivo. PMID- 1304209 TI - [Measuring scattered light with the Opacity Lensmeter 701 in normal eyes and eyes with cataracts. Correlation between scattered light and cataract-induced vision loss]. AB - In 50 eyes with nuclear cataract, posterior subcapsular cataract and cortical cataract and 34 normal eyes, the amount of scattered light was determined using the Opacity Lensmeter 701 to determine its accuracy in distinguishing between clear and cataractous lenses. Taking as a basis the manufacturer's statement that normal lenses show Opacity Lensmeter readings of less than 25 and that cataractous lenses show Opacity Lensmeter readings of more than 30, 94% of the nuclear cataract cases, 62% of the posterior subcapsular cases and 66% of the cortical cataract cases were identified as being pathologically opaque. Of the normal eyes, 88% had an Opacity Lensmeter reading of less than 25. Among the types of cataract examined, a significant linear relationship (P < 0.05) between visual acuity loss due to cataract and scattered light measurements could be found only in eyes with nuclear cataract, with the individual results heavily scattered around the linear regression. In the case of nuclear cataracts, measuring scattered light with the Opacity Lensmeter is suitable for making general statements on visual loss due to cataract for a whole group of patients. However, in individual cases the results can only be used together with other clinical examinations. PMID- 1304210 TI - [Postoperative astigmatism. 3.5 mm scleral tunnel incision and implantation of a HEMA posterior chamber lens vs 7 mm scleral step incision and implantation of a PMMA posterior chamber lens]. AB - In a prospective study, two groups of 35 patients each were compared following phacoemulsification and posterior lens implantation. Both groups were followed up to evaluate the evolution of the postoperative astigmatism during a minimum of 6 months. In group A, a HEMA posterior chamber lens was implanted through a 3.5 mm scleral tunnel incision. In group B, a PMMA posterior chamber lens was implanted through a 7 mm scleral step incision. The data were analyzed for the whole observation time with reference to preoperative, early postoperative, absolute and induced astigmatism. Different subgroups were formed. Vector analysis was performed in both groups in order to determine surgically induced axial changes, e.g., the intensity and direction of the power working on the cornea. The results were compared. Group A showed lesser early postoperative astigmatism than group B; however, group A also returned to the preoperative values more quickly. Both groups exhibited a shift towards against-the-rule astigmatism. PMID- 1304211 TI - [Risk of dislocation and cataract formation in 240 IOGEL lenses. 4 years experiences]. AB - Following planned extracapsular cataract extractions we implanted 240 IOGEL lenses into the capsular bag and noticed 5 dislocations into the vitreous cavity, 2 after an Nd-YAG capsulotomy, 4 postoperatively and 1 after surgical repositioning. Postoperatively, one lens was subluxated into the anterior chamber. Thirty-three patients required a 4- to 5-mm Nd-YAG capsulotomy because of a fibrotic or regenerative secondary cataract. Two lenses dislocated 2 and 6 weeks after the YAG capsulotomy into the vitreous cavity; the capsulotomy was performed 5 and 6 months, respectively, after the implantation. In 4 patients the IOGEL lens dislocated 3 times within the first 3 days and once within the first 3 months after implantation. Primary stable placement in the bag could be achieved, however. One patient required repositioning of the lens because of decentration 3 months after implantation. The lens dislocated on the following day. Late dislocation of the flexible and soft IOGEL lens can be due to the fact that the lenses do not adhere to the capsular sheets. Furthermore, postoperative capsular shrinkage enlarging a posterior capsular opening leads to lens dislocation. Eight patients underwent a secondary anterior chamber lens implantation. In three patients the IOGEL lens was explanted, in two of them without and in one of them with serious complications. The other five patients still have their IOGEL lens deep in the vitreous without complications. We suggest that if a YAG capsulotomy is necessary, it should not be performed before the 6th postoperative month. It should also not exceed 4 mm in diameter and no IOGEL lens should be implanted if a capsular rupture occurs intraoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304212 TI - [Effect of 0.1% dexamethasone and 1.0% prednisolone acetate eyedrops on the blood aqueous humor barrier]. AB - In a randomized, double-blind clinical trial we studied the protective effect of prednisolone-acetate 1.0% and dexamethasone 0.1% on the blood-aqueous barrier after cataract-extraction and posterior chamber lens implantation. Pre- and postoperative anterior chamber fluorophotometry was performed after i.v. administration of 10% fluorescein-sodium in 20 eyes of 20 patients of whom 16 finished the study (mean age 68.7 +/- 11.0; 13 female, 3 male). The topical application of either drug 5 times daily for 5 days did show a significant difference in surgery mediated disturbance of BAB in each group before and after phacoemulsification. However, when comparing the effect of the two drugs with each other, a difference could not be detected (p = 0.35). To attain a statistical 95% probability that there is no significant difference between the two treatment groups, a number of 690 patients would have had to be investigated. The results can be interpreted as to be due to a better cornea penetration of prednisolone-acetate which compensate the higher glucocorticoid-potency and receptor-affinity of dexamethasone. The untreated fellow-eyes did not reveal a significant difference between the pre- and postoperative anterior chamber fluorescein-concentrations in either treatment group. Anterior chamber fluorophotometry is able to demonstrate the potency and influence of both prednisolone-acetate 1.0% and dexamethasone 0.1% eye-drops on the BAB following phacoemulsification and IOL-implantation. The difference of both drugs does not seem to be of clinical importance in this context. PMID- 1304213 TI - [Spontaneous fracture of an implanted anterior chamber lens]. AB - This report deals with an 83-year-old patient who presented with visual deterioration. The patient had had an intracapsulary extraction with anterior chamber lens implantation. The break in the anterior chamber lens happened without any history of traumatic accident and led to dislocation of the lens and corneal decompensation. Scanning electron microscopy of the break area after explantation of the fragments revealed changes in the break zone that were characteristic of alternating tensile and compressive stress. Localization of the break at the transition of the optical part and the haptic where there is the greatest stress in the material points to insufficient strengthening in this critical part of the intraocular lens. PMID- 1304214 TI - [Capsulorhexis using an ultrasound-controlled cannula]. AB - Every cataract surgeon performing phacoemulsification has unintentionally damaged the posterior capsule. Thus he knows that the device is suitable for cutting the lens capsule. In recent years, I have performed various modifications of capsulorhexis with the aid of an ultrasound-guided cannula in all patients undergoing phacoemulsification. The following method proved to be practicable: The ultrasound-guided cannula is pressed on the lens capsule at 12 o'clock, thus opening the anterior capsule; the cannula is consecutively guided in two semicircular movements from 12 o'clock to 6 o'clock, and the anterior capsula is torn and cut open by directing the opening of the cannula toward the center of the pupil and simultaneously on the anterior capsula and away from the iris, thus making it possible to cut directly at the pupillary margin without damaging the iris. The anterior capsular tear has a smooth circular edge at the intersection of the two semicircles of the capsulorhexis, while a triangular flap directed towards the center of the pupil is often formed at 12 o'clock. At the end of phacoemulsification, the flap is aspirated with the suction rinsing device and cut off with a sharp cannula. This procedure simplifies and accelerates phacoemulsification. PMID- 1304215 TI - [IOL and aniseikonia calculation combined with documentation of surgical data and IOL inventory]. AB - The exact recording of operation data is a precondition for keeping the standards high in cataract surgery, but surgeons are reluctant to answer a questionnaire after a strenuous operation. We have designed a program easy to use in the Macintosh Hypercard System that covers all aspects of cataract surgery such as: (1) the operating record; (2) a data sheet for recording the various details of the operation; (3) recording of the data on hard disc; (4) managing the IOL stock list; (5) proposal of IOL models that are in stock with regard to IOL power (SRK2) and aniseiconia. This program enables the surgeon to record the operation data with effortless ease and it is well accepted. There is no dictation. The operating record and data sheet are printed immediately. The program is controlled by a "mouse". Selection of the suitable IOL model is facilitated by the link between the calculation of IOL power and the IOL stock list. In special cases the IOL power can be changed to obtain less aniseiconia. PMID- 1304216 TI - [Eye manifestations of Lyme borreliosis]. PMID- 1304217 TI - [Drusen in Bruch's membrane. Their significance for the pathogenesis and therapy of age-associated macular degeneration]. AB - The drusen found in Bruch's membrane represent precursors for the development of age-related macular degeneration. The pathogenetic concepts are summarized: 1. As a result of aging changes in the metabolism of the pigment epithelium with age, the normal structure of Bruch's membrane is destroyed. This process is associated with lipid accumulation and the development of drusen. The lipids deposited are predominantly phospholipids or neutral lipids. 2. The clinical appearance of drusen can also vary from one person to another, but individually a significant symmetry of drusen characteristics can be seen, demonstrating that drusen are the results of specific metabolic dysfunctions rather than non-specific aging products. 3. The development of specific forms of age-related macular degeneration corresponds with different drusen. Larger, more confluent and hypofluorescent drusen are associated with the development of pigment epithelium detachments. In eyes with smaller, scattered and hyperfluorescent drusen, choroidal neovascularizations are more likely. 4. Histochemically, larger, hypofluorescent drusen contain predominantly neutral lipids. In contrast, smaller, hyperfluorescent drusen consist predominantly of phospholipids. 5. The accumulation of neutral lipids in Bruch's membrane is therefore associated with Pigment epithelium detachments. These apolar lipids may produce a hydrophobic barrier in Bruch's membrane for the water transport from the retina towards the choroid. A pigment epithelium detachment can develop. 6. The deposition of polar phospholipids predisposes to the development of choroidal neovascularization. These lipids in association with the changed structure of Bruch's membrane may induce an inflammation--like reaction, resulting in the in-growth of choroidal capillaries under the pigment epithelium. The analysis of the relationship between subclinical aging changes in Bruch's membrane and different forms of age related macular degeneration may help to identify specific risk factors and to predict the future outcome in individual eyes. This may result in differentiated treatment concepts adapted to the specific aging changes in each person. PMID- 1304218 TI - [Idiopathic proliferative vitreoretinopathy. Activation of microglial cells as the deciding factor]. AB - Mononuclear phagocytes are considered pacemakers in the pathogenesis of proliferative vitreoretinopathy (PVR), but their precise biological origin in preretinal PVR traction membranes has remained obscure. This study presents a combined immunohistochemical protocol for the detection of microglial cells, which was applied to 37 membranes of patients with idiopathic and traumatic PVR and with proliferative diabetic retinopathy (PDR). Microglial cells may be labeled by staining for LN-1, ricinus communis agglutinin-(RCA)-1, vimentin, HLA DR-II, and nucleoside diphosphatase, but are negative for Leu-M1, Leu-M3, EBM-11, von Willebrand factor, CD22, cytokeratin, and glial fibrillary acidic protein (GFAP). Significant proliferation of microglial cells was found in idiopathic PVR while classical macrophages were typical of traumatic PVR. Only rarely were microglial cells detected in PDR. These findings bring into question previous concepts of the pathobiology of idiopathic PVR and support the hypothesis of idiopathic PVR as a specific disease entity. PMID- 1304219 TI - [Selective occlusion of ocular neovascularization by photodynamic therapy]. AB - Photodynamic therapy (PDT) has successfully been used to induce vascular occlusion via endothelial damage and subsequent thrombosis. To increase the selective of this method for neovascularizations, characteristics in the ultrastructure of the proliferative vessel wall allow physiological vessels to be spared and predominantly neovascularizations to be occluded: (a) Due to the disturbance of the blood-retina barrier, free dye molecules accumulate within the vascular wall. Using a dye with prolonged retention, such as phthalocyanine (CASPc), it is possible to thrombose neovascularizations 24 h post injection while leaving the physiological vasculature of the anterior segment of the rabbit eye unaffected. (b) Proliferating endothelial cells express high numbers of low density lipoprotein (LDL) receptors. Chlorin e6 (Ce6), a potent photosensitizer, is covalently bound to LDL. Intravascularly, ce6-LDL complexes selectively label neovascular walls. Since ce6-LDL is incorporated intracellular into enzymatically active lysosomes, photothrombosis is effectively achieved at low drug and light doses in vivo. In addition, the induced damage is spatially confined to the inner vascular lining. We conclude that carrier-mediated PDT may offer a new and sensitive approach for selective treatment of intraocular neovascularizations. PMID- 1304220 TI - [Early disorders of retinal function in diabetes mellitus]. AB - Thirteen insulin-dependent diabetics, aged 13-30 (mean 19.15) years, entered the study. Patients with retinal ischemia, vascular proliferation, or a Snellen acuity below 0.8 were excluded. Ten normal untrained subjects, aged 20-30 (mean 24) years, provided the normal sample. The battery of special visual function tests consisted of: (1) high luminance Pfluger acuity (acuity/luminance/function, rotatable illiterate "E optotypes, screen luminance 10,000 cd/m2); (2) tests combining color vision with demands on spatial resolution: (a) blue-green chromatic acuity (a Velhagen pseudoisochromatic plate served as optotype, the maximum recognition distance being recorded); (b) standard vs mini-panel D-15 color-arrangement tests; (c) blue preferential computerized perimetry (modified Tubingen automatic perimeter, orange adaptive illumination, Schott cut-off filter OG 550, cupola luminance 5 cd/m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304221 TI - [Model experiments of the outer blood-retinal barrier in vitro]. AB - Because of the difficulty in conducting experiments on the outer blood-retinal barrier in vivo, we developed an in vitro model. Bovine retinal pigment epithelial cells were grown on semipermeable membranes, enabling separate manipulation of the apical and basal medium. As a parameter of barrier function, we measured the transepithelial resistance (TER). Barrier function was also tested with fluorescein. The transepithelial resistance increased under optimal culture conditions, in confluent cultures, by 200 omega and there was no fluorescein leakage. After exposure to trypsin in Ca/Mg-less medium or EDTA or after application of argon laser, we were able to induce a breakdown of the TER and fluorescein leakage. This happened immediately after laser exposure, 1 min after EDTA, and 4 min after trypsin application. We observed no morphological differences after breakdown of the barrier function on the intercellular connections compared to normal confluent cultures following EDTA or trypsin exposure. In all experiments there was a recovery of barrier function after returning the cells to control conditions. These first results demonstrate that our in vitro model is a sensitive method for investigating barrier function in retinal pigment epithelium in cell culture. PMID- 1304222 TI - [Changes in the invasion front of uveal melanomas]. AB - Central and peripheral cells of 12 uveal melanomas were compared by electron microscopy to determine whether infiltrating melanoma cells have special characteristics (e.g., loss of cell adherence, changes in the cytoskeleton, increase of cell organelles). No significant differences were found. The two theories of tumor invasion ("mechanical" and "locomotive" theory) and the light microscopical findings that occur in the invasion zone of uveal melanomas are discussed. PMID- 1304223 TI - [Cyclosporin A in therapy of chronic uveitis]. AB - 48 patients with chronic severe uveitis of pressumed noninfectious origin resistent to corticosteroids have been treated with Cyclosporin A. All patients had an initial loading dose of 5 mg/kg/day followed by a dose reduction according to ocular inflammatory activity and tolerability and according the guidelines by BenEzra, Nussenblatt and Timonen. Most of the patients received additional corticosteroids in a low dose. 35 out of these 48 patients (13 suffering from intermediate uveitis, 11 from retinal vasculitis, 5 panuveitis, 4 "pressumed histoplasmosis" and 2 sympathetic ophthalmia) were treated for 1 year and observed after withdrawing of Sandimmun for at least 6 months. The majority of these patients have manifested a positive therapeutic response to Cyclosporine, in particular patients suffering from vasculitis, panuveitis and sympathetic ophthalmia. All 35 patients were treated before for a long time with steroids without success, 19 out of these 35 in addition with cytotoxic agents. The immunosuppressive effect of Cyclosporine was not permanent, frequently the inflammation relapsed on reduction of dosage or withdrawing of the drug. Guidelines for combined regimen (Cyclosporine and corticosteroids and vitrectomy) were given. Although a large variety of side effects were reported the compliance was good. PMID- 1304224 TI - [Acute necrotizing retinitis with amotio retinae. Surgical and medicamentous antiviral therapy]. AB - This report pertains to the case of a 25-year-old patient suffering from acute necrotizing retinitis (ANR syndrome). Initially, one eye revealed clinical signs of diffuse chorioretinitis accompanied by perivasculitis and heavy keratic precipitates, papillitis, and vitreous infiltrates. After initial improvement under antiphlogistic therapy, however, necrotizing retinitis developed, associated with peripapillar hemorrhages, multiple peripheral retinal holes and eventually complete retinal detachment. The subsequently performed retinal detachment surgery, completed with vitrectomy, cerclage and silicone oil tamponade, was successful. At the same time, the patient was put on systemic therapy based on acyclovir. In the literature, similar developments are usually related to HSV and HZV infections. Although in our case a virological diagnostic test did not reveal the presence of any virus, the characteristic symptoms of the ANR syndrome completely disappeared under the above-mentioned therapy. Visual acuity, previously consisting only in light perception, improved to 0.4. PMID- 1304225 TI - [Leopard spot chorioretinopathy. Initial manifestation of recurrent acute lymphocytic leukemia]. AB - An 11-year-old girl with a history of acute lymphocytic leukemia of the central nervous system had attained complete remission for almost 3 1/2 years after combination chemotherapy and radiotherapy when she developed iritis and chorioretinopathy of the right eye. Neither an anterior chamber tap nor a diagnostic vitrectomy revealed leukemic cells. Both nonspecific anti-inflammatory therapy and antiviral treatment were unsuccessful. Finally, lymphoblasts were detected in the cerebrospinal fluid and in the bone marrow after repeated lumbar puncture and bone marrow aspiration. Combination chemotherapy alone was resumed, resulting in the resolution of all acute ocular symptoms and bone marrow involvement. Only the leopard-spot-like pigmentary fundus changes persisted. The child has now remained in continuous complete remission for 1 1/2 years. PMID- 1304226 TI - [Measuring retinal vascular diameter using the scanning laser ophthalmoscope and computer. Initial results]. AB - The diameter of the large retinal vessels is an important factor in retinal microcirculation. A system configuration was developed that uses SLO images to measure the diameter of retinal branch vessels off-line. The place for measurement is defined in the image by the investigator, and the diameter is measured automatically. The mean standard deviation of the diameter of arterial vessels was 2.37% and for veins 3.43% by repeat measurement in sequential pictures by optimal scanner settings. The reproduction of vessel diameters was unsatisfactorily for repeat examinations. The course of these results may be changes in the fundus image connected with changes in the position of the scanner bulbus (e.g., new examination, poor fixation). The scanner-bulbus position is not yet precisely defined and not reproducible enough. PMID- 1304227 TI - [Krypton laser therapy. Use in secondary serous detachment of the retinal pigment epithelium and in multiple idiopathic serous detachments of the retinal pigment epithelium]. AB - Two variants of serious detachments of the retinal pigment epithelium (RPE) are demonstrated with reports of typical cases: (1) secondary serous detachment of the RPE; (2) idiopathic serous detachment of the RPE (pigment epithelium detachment not associated with any other retinal or choroidal disease). Fluorescein angiographic criteria for differential diagnosis and the resulting different techniques of krypton laser coagulation are portrayed: (a) focal krypton laser coagulation of the total area of the pigment epithelium detachment; (b) circular, one-row laser coagulation at the detachment borders. The advantages of circular, one-row laser coagulation of idiopathic serous RPE detachment over coagulation of the total area of the RPE detachment are described: first, these are fewer scotomas following coagulation; second, fewer laser foci are required; and third, the risk of subretinal bleeding is lower. These findings emphasize the efficiency of circular, one-row laser coagulation at the detachment borders in the treatment of idiopathic serous RPE detachments. PMID- 1304228 TI - [Tubulointerstitial nephritis and uveitis (TINU syndrome)]. AB - We report on a case of non-granulomatous bilateral iridocyclitis with tubulointerstitial nephritis in a 13-year-old girl. Complete recovery was achieved after treatment with systemic and topical corticosteroids. PMID- 1304229 TI - Selenium in the treatment of heavy metal poisoning and chemical carcinogenesis. AB - Selenium (Se) has been shown to counteract the toxicity of heavy metals such as cadmium, inorganic mercury, methylmercury, thallium and to a limited extent silver. Although not as effective as Se, vitamin E significantly alters methylmercury toxicity and is more effective than Se against silver toxicity. Vitamin E is very effective against lead toxicity but Se has little effect. The presumed protective effect of Se against cadmium and mercury toxicity is through the diversion in their binding from low molecular weight proteins to higher molecular weight ones. Se appears effective in counteracting the chemical carcinogens (3-methyl-4-dimethyl-aminoazobenzene, 2-acetylaminofluorene, diethylnitrosamine, aflatoxin, 7,12-dimethylben (a) anthracene, benzopyrene and 3 methylcholanthrene) used to induce skin, liver and mammary tumors, but much less effective against those (dimethylhydrazine, azoxymethane, methylazoxymethanol, bis (2-oxopropyl) nitrosamine, benzopyrene, 1 methyl-1-nitrosourea and n-methyl-n nitro-nitrosoguanidine) used to produce tumors in the colon, lungs, trachea and pancreas in laboratory animals. In contrast, Se many even increase pancreatic carcinomas in animals treated with bis (2-oxopropyl) nitrosamine. The health implications in humans of Se and heavy metal toxicities and in cancer are discussed. PMID- 1304230 TI - Concentration of free calcium in erythrocytes and liver mitochondria of zinc depleted rats. AB - The concentration of Ca(2+)-ions in mitochondria and erythrocytes of zinc depleted rats was determined with the fluorescent Ca(2+)-indicator fura-2. The zinc-concentration of the diet did not affect the mitochondrial Ca(2+) concentration. There was an elevation of 5% for the Ca(2+)-concentration in erythrocytes of zinc-depleted and pair-fed rats compared to ad libitum-fed animals. The cause of this elevation could be ATP-depletion because of restricted food intake. PMID- 1304231 TI - Transplacental passage and fetal deposition of mercury after low-level exposure to methylmercury--effect of seleno-L-methionine. AB - Previous experimental studies on transplacental passage and possible fetotoxicity of methylmercury have almost exclusively used a single dosage or 2-4 repeated doses of mercury on specific days during gestation and often used at relatively high dose levels. In previous studies, selenium supplementation considerably increased the concentration of mercury in the blood of offspring after maternal exposure of rats to methylmercury, whereas whole-body retention and organ deposition of mercury in mice were unaffected. The present study in mice, which involved exposure for 5 weeks to a low dose of methylmercury in the drinking water (1 nmol/ml) before and during pregnancy, demonstrates that mercury is deposited in offspring both in utero and during lactation, and that transplacentally absorbed mercury is not, or only very slowly, excreted. Seleno-L methionine increased the deposition of mercury in offspring, but the effect was due to slightly higher deposition in the dams. Selenomethionine significantly reduced the kidney deposition of mercury in offspring, whereas liver deposition of mercury was unaffected. These results indicate that interactions between organo-selenium compounds and methylmercury orally administered at low doses is of less importance than previously believed on the basis of experiments with higher doses of selenite injected or supplemented to the diet. PMID- 1304232 TI - The human selenium status in Hungary. AB - The selenium concentration of foods and of human blood varies widely between geographical areas depending on the availability of soil Se for plants. The mean serum Se concentration in Europe has been found to vary between 0.80-1.50 mumol/l and the mean Se concentration of wheat between 0.02-0.11 mg/kg. We estimated by various markers the Se status of Hungarians on whom data is lacking. Serum samples (n = 238) from healthy blood donors, and toenails (n = 132) and fingernails (n = 211) from different apparently healthy individuals residing in both urban and rural areas were collected from four districts in Hungary. Wheat samples (n = 29) as grains were obtained directly from farms representing the same areas. Serum Se was determined by electrothermal AAS and the other samples by acid-digestion fluorimetry. The accuracy of the methods was verified by analyzing external reference samples. The mean (+/- SD) serum Se concentration was 0.70 +/- 0.12 mumol/l, ranging between 0.41-1.18 mumol/l. The mean serum Se levels 0.87 mumol/l was significantly (p < 0.001) higher in the East and lower in the South (0.60 mumol/l) compared to the northern area 0.70 mumol/l. The mean (+/ SD) toenail Se concentration was 0.56 +/- 0.18 mg/kg. The Se level in the East was significantly (p < 0.01) higher than the level in the North, 0.68 mg/kg vs. 0.54 mg/kg, respectively, and lowest in the southern area, 0.40 mg/kg. The same pattern applied to fingernails. Wheat Se ranged from 5 to 235 micrograms/kg, with the median 34 micrograms/kg. The lowest Se concentrations were generally found in the South.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304233 TI - Nickel-, chrom- and cobalt-concentrations in human tissue and body fluids of hip prosthesis patients. AB - The world-wide experience with millions of metallic implantations suggests the biocompatibility of modern alloys, commonly made of cobalt, chromium and nickel. There is, however, little information available on the internal metal exposure resulting from implants. In this study we assessed the metal concentrations in body fluids and tissue samples (muscle, bone) of patients who had undergone total hip replacement. Our patients were divided up into two groups. One group had firmly fixed implants two years after surgery. The other group had loose implants of the same Co-Cr-Mo alloy. Urine analyses revealed an increased renal elimination of nickel, chromium and cobalt. Cobalt and nickel exceeded the upper normal value. In serum the concentrations of nickel and chromium were normal or slightly elevated, the cobalt concentrations were significantly elevated. In some cases tissues adjacent to the implant showed extremely high concentrations of chromium and cobalt. This finding was also obtained in tissues that had no direct contact with the arthroplasty. The findings suggest that alloys of prostheses can undergo corrosion and release metal ions. PMID- 1304234 TI - Chromatographic separation of serum proteins and estimation of their zinc and copper content. AB - Human serum proteins of blood donors and dialysis patients were separated by means of gel filtration chromatography. The resulting fractions were analyzed for copper and zinc. Separation resulted in 3 zinc peaks with a molecular weight of about 700,000, 300,000, and 75,000 Dalton, with alpha 2-macroglobulin co-eluting in the first and albumin co-eluting in the third zinc peak. The zinc protein(s) of the second peak remained unidentified. The three peaks contained, in succession, 0.72 +/- 0.30 mumol/L (4.8 +/- 1.6%), 1.26 +/- 0.37 mumol/L (8.5 +/- 1.7/1000) and 12.8 +/- 2.1 mumol/L (86.8 +/- 2.8%) of total zinc in the case of blood donors, and 1.19 +/- 1.05 mumol/L (9.2 +/- 7.2%), 0.97 +/- 0.22 mumol/L (8.0 +/- 2.6%), and 10.4 +/- 1.66 mumol/L (82.7 +/- 6.7%) in the case of dialysis patients. Separation followed by copper analysis resulted in the three peaks, as well, with a molecular weight of about 750,000, 140,000, and 75,000 dalton. The copper protein of the first peak remained unidentified, while coeruloplasmin co eluted in the second and albumin in the third peak. The three peaks contained, in succession, 0.4 +/- 0.16 mumol/L (2.3 +/- 0.95%), 14.6 +/- 0.7 mumol/L (83.9 +/- 4.1%), and 2.4 +/- 0.6 mumol/L (13.7 +/- 3.5%) of total copper in the case of blood donors, and 0.5 +/- 0.73 mumol/L (2.2 +/- 3.2%), 19.5 +/- 1.1 mumol/L (90.5 +/- 4.9%), and 1.6 +/- 0.66 mumol/L (7.3 +/- 3.0/1000) in the case of dialysis patients. Limitation of the method is shown regarding separation of major from minor proteins and albumin from transferrin. PMID- 1304236 TI - Review of publications. PMID- 1304235 TI - Detection by HPLC-ICP of metallothionein in serum of an epileptic child with valproate-associated hepatotoxicity. AB - A patient who developed valproate-associated hepatotoxicity had significantly lower serum levels of total protein, albumin and selenium than the controls. This study shows that with the beginning of the hepatic coma metallothionein (MT) appeared in the serum mainly in the form of Zn-thionein, which altered the Zn distribution pattern of the serum in a characteristic manner. HPLC-ICP3 was successfully applied to the simultaneous speciation of elements and characterization of MT by the use of one gel permeation column. PMID- 1304237 TI - Arthroscopic surgery. PMID- 1304238 TI - Cyclophosphamide cardiotoxicity. PMID- 1304239 TI - The trade in human organs. PMID- 1304240 TI - Intensive lipid lowering therapy and atherosclerosis. PMID- 1304241 TI - Post-angiographic femoral artery injuries. PMID- 1304242 TI - Gastric cancer and surgical workload. PMID- 1304243 TI - Left ventricular mass and geometry in essential hypertension. PMID- 1304244 TI - A young female with intestinal obstruction, headache and vomiting. PMID- 1304245 TI - Amniocentesis. PMID- 1304246 TI - Management of intrauterine foetal death. PMID- 1304247 TI - Maurice King replies. PMID- 1304248 TI - More on 'human entrapment ...'. PMID- 1304249 TI - More on "human entrapment ...'. PMID- 1304250 TI - More on "human entrapment ...'. PMID- 1304251 TI - Changing convictions with changing journals? PMID- 1304252 TI - HBV transmission in healthy persons at high risk in India. PMID- 1304254 TI - National Medical Library. PMID- 1304253 TI - Postictal hyperprolactinaemia. PMID- 1304255 TI - Multi-resistant typhoid fever. PMID- 1304256 TI - Patient service or patient care? PMID- 1304257 TI - The right to die. PMID- 1304258 TI - Doctors on strike. PMID- 1304259 TI - Detection of hepatitis B virus DNA in donor blood by the polymerase chain reaction. AB - BACKGROUND: Blood collected from voluntary donors at local blood banks and blood donation camps was screened for the hepatitis B virus genome using the polymerase chain reaction and for viral markers by standard serological techniques. The sensitivities of the two screening strategies were compared. METHODS: One hundred and twenty-six blood samples were tested for HBV serological markers--HBsAg, anti Hbs and anti-HBc--by ELISA: The same samples were also subjected to the polymerase chain reaction using primers made by us. RESULTS: Analysis of the polymerase chain reaction amplified products revealed that 24% of the blood samples which tested negative for HBsAg using the ELISA technique were positive for HBV DNA by the polymerase chain reaction. All the HBsAg positive samples (by ELISA) were also positive by the polymerase chain reaction (which detected additional samples as well). Anti-HBc antibodies showed a much greater concordance with the polymerase chain reaction. CONCLUSIONS: The results emphasize that the screening strategies for donor blood need to be re-evaluated in order to check inadvertent transmission of hepatitis B virus during blood transfusion. The ELISA technique to detect HBsAg as the sole serological marker is inadequate to indicate the actual prevalence of hepatitis B virus in the donor blood. The polymerase chain reaction may be a better screening test. If this is not available, the detection of anti-HBc antibodies appear to be a better means of screening blood than HBsAg. PMID- 1304260 TI - HLA and complement C4 studies in psoriasis vulgaris. AB - BACKGROUND: Psoriasis vulgaris is known to be associated with the presence of certain HLA antigens and complement factors but only studies of Western populations have been reported. We investigated the HLA and complement profile in Indian patients with psoriasis vulgaris. METHODS: Sixty-seven patients and 132 normal subjects were typed for class I antigens using 262 sera, and 55 patients and 104 normal subjects were typed for class II antigens using 174 sera. The sera from patients and normals were sent to Japanese laboratories for the study of class III antigens. RESULTS: The study revealed that patients had an increased frequency of A1 (p < 0.0025), B17 (p < 0.0025), Cw6 (p < 0.001) DR7 (p < 0.05) and DQw3 (p < 0.005) when compared to normal controls. Analysis of two and three antigen haplotypes revealed a significant increase in the incidence of all haplotypes involving those antigens which showed a high frequency among patients. A significant association was also found with complement factors C4A6.3 and C4A6,X. However, the relative risk was high for C4BQO (10.73). CONCLUSIONS: Psoriasis in Indians is associated with the A1, B17 and Cw6 but not with B13 antigens and the complement allotypes mentioned above. The strong association with C4 factors may be as a result of a close linkage between the class III region and Ir genes. PMID- 1304262 TI - Surgical audit. PMID- 1304261 TI - Infections and vitamin A. PMID- 1304263 TI - Percutaneous endoscopic gastrostomy for long term enteral nutrition. AB - BACKGROUND: Percutaneous endoscopic gastrostomy for long term enteral nutrition is often indicated in patients with head, neck and oesophageal cancer but despite its growing popularity elsewhere, it is not widely used in India. METHODS: Between March 1990 and July 1991, we performed percutaneous endoscopic gastrostomy in 54 patients. The primary sites of tumour were the hypopharynx (11), oral cavity (7), tongue (7), cricopharynx (7), oesophagus (16) and other sites (6). The indications were difficulty in swallowing following treatment (22), preoperative nutritional support (7) and terminal care (21). In 49 patients, it was performed by the 'pull' technique in the endoscopy room under local anaesthesia and mild sedation. Indigenously prepared tubes and blenderised foods were used. Fifteen patients underwent dilatation of the tumour prior to the gastrostomy. RESULTS: The procedure was successful in 50 (93%) patients. Three failures were caused by obstructing tumours and one by a previous gastric resection. Feeding was started 18 to 24 hours after the procedure in 48 patients. No major complications occurred but minor complications were seen in 11 (22%) patients. Fourteen patients had their gastrostomy tube removed after 2 to 6 months of use while 15 patients undergoing therapy or with persistent dysphagia were on gastrostomy feeds for 1 to 6 months. Of the 21 terminally ill patients, 8 died, 6 were lost to follow up and 7 were on feeds for 1 to 6 months. CONCLUSIONS: Percutaneous endoscopic gastrostomy is a simple, safe and effective method for long term enteral feeding. Indigenous tubes and home made blenderised foods are adequate substitutes for the more expensive commercial kits and enteral formulations. PMID- 1304265 TI - Malarial hepatitis: a heterogeneous syndrome? AB - BACKGROUND: The incidence of malarial hepatitis in patients with Plasmodium falciparum infection and jaundice is not known and it is not clear whether the condition is a single entity or a heterogeneous syndrome. METHODS: We prospectively studied the natural history of all patients with falciparum malaria and jaundice admitted to military hospitals in Northeast India from 1988 to 1991. A possible drug or viral cause for the hepatitis was excluded by the history, serological tests and liver histology. RESULTS: Of the 732 patients admitted with falciparum malaria, 39 had jaundice but only 18 had malarial hepatitis indicated by a rise in their serum glutamate pyruvate transaminase levels to more than three times the upper limit of normal and an absence of clinical or serological evidence to suggest drug or viral hepatitis. The liver in these patients was always enlarged. Their mean age was 27.6 years and 85% were males. The mean serum bilirubin was 12.7 +/- 10.3 mg/dl, serum glutamate oxaloacetate transaminase was 212.8 +/- 144.9 IU, serum glutamate pyruvate transaminase was 287.1 +/- 206.2 IU and the serum alkaline phosphatase was 20.4 +/- 10.1 KA. Clinically, 2 groups of patients were seen. Thirteen patients who presented with a severe form of disease had coma, deep jaundice and renal failure. The other 5 patients had a relatively mild illness with only fever, headache and vomiting for 2 days. Four patients with severe disease died. Liver histology (studied in 5 patients) showed Kupffer cell hyperplasia and deposition of malarial pigment. Plasmodium falciparum was demonstrated in sinusoidal red blood cells in only 2 cases. CONCLUSIONS: Malarial hepatitis occurred in 18 out of 39 patients with jaundice and falciparum malaria. It is a heterogeneous syndrome with at least two clinical subsets and the severe disease should not be mistaken for fulminant hepatic failure as there is a better response to therapy. PMID- 1304264 TI - Enteral nutrition in surgical patients. AB - BACKGROUND: Malnutrition is common in patients admitted for surgery and is a major cause of increased morbidity and mortality. Nutritional support has been shown to be of help in reducing complications. Parenteral nutrition and commercially available enteral diets are expensive, so the efficacy of a 'home brew' enteral diet was studied in such patients. METHODS: Forty malnourished patients, 20 with benign disease and 20 with malignancy, were administered a 'home-brew' enteral diet (1140 calories and 60 g protein per litre) perioperatively for 14 days. They received 2500 to 4000 calories per day according to their requirement. Weight, triceps skinfold thickness, midarm circumference, serum albumin and transferrin, absolute lymphocyte count and creatinine-height index were monitored on days 0, 7 and 14. Nitrogen balance was estimated on alternate days and the results of the two groups were compared. RESULTS: Weight, skinfold thickness and midarm circumference did not change. Serum albumin levels showed a rise in the benign group by day 7, but the rise attained significance in the malignancy group by day 14. A similar pattern was observed in transferrin levels and there was a significant correlation (r = 0.652, p < 0.001) between albumin and transferrin levels. A positive nitrogen balance was attained earlier in the benign group (4.3 v. 5.8 days, p < 0.001). The creatinine-height index showed a rise in both groups by day 7 and a further rise by day 14. Diarrhoea was the commonest complication but was easily controlled with loperamide. The efficacy of the diet was evidenced by the improvement recorded in various objective nutritional parameters and complications were minimal. CONCLUSION: This cost-effective diet may be used for nutritional support with good results in patients in India and other developing countries. PMID- 1304266 TI - Molecular cytogenetics of human cancer. AB - Cancer may arise from the genetic transformation of a single precursor cell, which proliferates to form a clone. Chromosomal abnormalities are associated with many types of tumours. Some of the chromosomal rearrangements such as translocation, deletion and insertion involve breakage of chromosomes close to known oncogenes. The close linkage between the chromosomal changes, the gene modifications and consequently altered protein function seen in malignant cells suggest that cancer is a genetic disease. Analysis of chromosomal abnormalities and oncogene amplifications in malignant cells have been found to be related to their malignant potential and hence may be utilized in the clinical management of patients with cancer. PMID- 1304268 TI - So you think it's safe to go into the water? PMID- 1304267 TI - Ranitidine in NSAID ulcers. PMID- 1304269 TI - Affluence and coronary risk. PMID- 1304270 TI - Another genetic basis for vascular disease. PMID- 1304271 TI - Tests of pulmonary function--I. PMID- 1304272 TI - Pleural aspiration and biopsy. PMID- 1304273 TI - Simplified methods for calculation of confidence intervals. PMID- 1304274 TI - Health care delivery in North America: politics and practice. PMID- 1304275 TI - The wilful, progressive, devaluation of public teaching hospitals. PMID- 1304276 TI - Multi-drug resistant Salmonella. PMID- 1304278 TI - Blood banks. PMID- 1304277 TI - Treatment of leprosy. PMID- 1304279 TI - Disinfecting drinking water. PMID- 1304280 TI - HIV surveillance. PMID- 1304281 TI - Assisted circulation using skeletal muscle. PMID- 1304282 TI - Daily diethylcarbamazine for the treatment of Brugia malayi microfilaria carriers. AB - BACKGROUND: Diethylcarbamazine is effective for the treatment of brugian filaria carriers. However, the 12-day course with a daily dose of 6 mg per kg body weight is rarely completed. The World Health Organization has indicated the need for better regimes to control filariasis. METHODS: We evaluated the long term effects of three different dosage regimes of diethylcarbamazine--6, 9 and 12 mg per kg body weight--to a total of 72 mg on 93 microfilaria carriers of Brugia malayi. RESULTS: All cases treated with the 6 mg daily dose showed complete clearance of microfilaria immediately after the treatment. However, at the 9 and 12 mg daily doses only 91% and 85% of cases respectively showed complete clearance. There was a close association between the daily dose and the proportion of cases developing side-effects. The mean initial microfilaria counts were significantly higher in those who had side-effects than in those who did not. An 11-month follow up showed that with the 6 mg daily dose the recurrence rate of microfilaraemia was 29% while with the 12 mg daily dose it was 67%. Four per cent of patients on a daily dose of 6 and 9 mg discontinued treatment while 21% of those on the 12 mg daily dose did so. CONCLUSION: The 6 mg daily dose of diethylcarbamazine was the most effective and best accepted regime. PMID- 1304283 TI - Iopanoic acid as an adjunct to carbimazole in the management of hyperthyroidism. AB - BACKGROUND: The thiourea drugs take a few weeks to control the symptoms of hyperthyroidism whilst iodine containing radiographic contrast agents (iopanoic acid and sodium ipodate) have a more rapid effect. There is no report on the use of iopanoic acid administered in conjunction with carbimazole, so we evaluated the efficacy of this combination in the early medical management of patients with hyperthyroidism. METHODS: Thirty hyperthyroid patients diagnosed by clinical and biochemical criteria were randomized into two treatment groups. Group A (n = 16) received iopanoic acid (500 mg orally twice a day for the first 3 weeks) and carbimazole (30 mg orally in three divided doses) while group B (n = 14) received carbimazole alone. Clinical examination and estimation of serum total T3, total T4 and TSH were done by radioimmunoassay at the start of therapy, weekly for 4 weeks and then at 6, 8 and 12 weeks. RESULTS: In the initial 3 weeks, iopanoic acid induced a significantly greater fall in mean serum total T3 levels (Z = 2.298, p < 0.02) and a slower fall in mean serum total T4 (Z = 2.396, p < 0.05) in group A patients compared to those in group B. This was accompanied by earlier clinical improvement in group A patients. The mean serum total T3 and T4 values rose to higher levels in group A at 4 weeks, one week after discontinuation of iopanoic acid. At the end of 12 weeks, however, there was no significant difference in the mean serum total T3 and T4 levels between the two groups (p > 0.05). Biochemical euthyroidism (i.e. total T3 < 3 nmol/L and total T4 < 170 nmol/L) was achieved later in group A patients than in group B (10.4 +/- 5.0 weeks v. 3.6 +/- 1.2 weeks, p < 0.0001). CONCLUSIONS: Iopanoic acid given together with carbimazole induces rapid clinical improvement in hyperthyroid patients than carbimazole alone. However, the delayed achievement of euthyroidism may preclude its routine use in the management of patients with hyperthyroidism except in those with thyrotoxic emergencies. PMID- 1304284 TI - Total cholesterol and mortality in patients with pre-existing coronary artery disease. AB - BACKGROUND: A positive correlation exists between serum cholesterol levels and cardiovascular mortality. However, the role of serum cholesterol in persons with pre-existing coronary artery disease is not clear. METHODS: A cohort of 524 patients with coronary artery disease was divided into four groups based on the total serum cholesterol values. Group I consisted of 68 patients with cholesterol levels of 200 mg/dl or less; Group II of 116 patients with cholesterol levels between 201 and 220 mg/dl; Group III of 187 patients with levels between 221 and 240 mg/dl and Group IV of 153 patients with cholesterol levels greater than 240 mg/dl. RESULTS: Actuarial survival analysis over an 11-year follow up did not show any overall difference in mortality between these groups (Logrank test statistic = 1.89, p > 0.1). Analysis after adjustment of the data also showed that mortality rates were not different (chi (2) = 4.73, p > 0.05). Hazard function analysis indicated that death rates per thousand person years of follow up were 49.97 +/- 8.4 in Group I, 41.38 +/- 8.4 in Group II, 55.39 +/- 4.4 in Group III and 45.38 +/- 6.4 in Group IV. These were also not statistically significant. Comparison of mortality rates in patients with angina pectoris and past myocardial infarction also showed similar results. CONCLUSION: Total serum cholesterol levels do not influence long term survival in patients with pre existing coronary artery disease. PMID- 1304285 TI - Polymerase chain reaction. PMID- 1304287 TI - Parental occupation and childhood cancer. PMID- 1304288 TI - Tests of pulmonary function--II. PMID- 1304286 TI - A substitute for human blood? PMID- 1304289 TI - Assessment of anterior pituitary function using the combined insulin stress test. PMID- 1304290 TI - Fraud in biomedical science. PMID- 1304291 TI - Silicone gel breast implants: the facts and the fury. PMID- 1304292 TI - Medical research in India. PMID- 1304293 TI - Liver transplantation in India. Can we? Should we? PMID- 1304294 TI - Leprosy vaccines. PMID- 1304295 TI - AIDS epidemic. PMID- 1304296 TI - Treatment of leprosy. PMID- 1304297 TI - Medical services and the Consumers Protection Act. PMID- 1304298 TI - The Dunkel draft--a prescription for disaster. PMID- 1304299 TI - Medical journals in the West and in India. PMID- 1304301 TI - The use of diagnostic bronchoscopy in lung cancer. AB - BACKGROUND: The role of fibreoptic bronchoscopy in the diagnosis of bronchogenic carcinoma is well established. However, in developing countries, where the burden of illness is large and diagnostic facilities are limited, only a small number of patients are diagnosed at a stage when they might benefit from operation. We felt it would be desirable to identify subsets of patients suspected of harbouring lung cancers, in whom bronchoscopy would have not only a high diagnostic yield but also provide useful information which might influence treatment, the patient's quality of life and duration of survival. METHOD: We analysed the records of 588 patients, who had been bronchoscoped for suspected lung cancer, over a period of 8 years at a tertiary referral centre in north India. The patients were divided into different clinical subgroups on the basis of their clinical and radiological presentation, and the diagnostic yield from bronchoscopy in each group was calculated. A decision analysis model was constructed and the expected value of clinical information was determined for each group. RESULTS: A tissue diagnosis was established by bronchoscopy in 177 (30%) patients and by additional investigations in 43 (7.3%) patients. A positive tissue diagnosis was obtained most often in patients with clinical and radiological evidence of pulmonary collapse (50%) and mass lesions (38-42%). Only 12% of patients with malignancy underwent resection and 70% of them belonged to the above two groups. The expected value of clinical information was greatest in patients with collapse (0.077) or mass lesions (0.067-0.065). CONCLUSIONS: A diagnostic work-up including fibreoptic bronchoscopy is indicated early in patients with collapse or mass lesions of the lung. Patients with non-resolving pneumonia, pleural effusion, metastatic disease and non-specific lesions on chest X-ray should receive a low priority for bronchoscopy. PMID- 1304300 TI - Prenatal diagnosis and control strategies for beta-thalassaemia on the Indian subcontinent. AB - BACKGROUND: The control of beta-thalassaemia by prenatal diagnosis is an important option in India. The disease is common and resources are scarce for the treatment of affected children. Presently the most suitable approach for prenatal diagnosis is DNA analysis of a chorion villus sample by direct mutation detection. For the implementation of such a prenatal diagnosis programme it is essential to know the spectrum of beta-thalassaemia mutations in the population. METHOD: The beta-thalassaemia mutations of 708 unrelated carriers from seven different regions of the Indian subcontinent were characterized by the allele specific polymerase chain reaction and DNA sequencing. RESULTS: Sixteen different beta-thalassaemia mutations were identified which could be divided into three groups according to their frequencies. Five common mutations accounted for 93% of alleles. Significant regional differences in the frequency and distribution of mutations were observed. CONCLUSIONS: The spectrum of mutations defined forms the basis for a beta-thalassaemia prenatal diagnosis programme in India. A strategy has been outlined for mutation detection which could be successfully applied. Since prenatal diagnosis has become comparatively simple, recommendations are made for a community-based thalassaemia control programme. PMID- 1304303 TI - Is vasectomy dangerous? PMID- 1304304 TI - Dilatation and curettage. PMID- 1304305 TI - Haemoptysis. PMID- 1304302 TI - T cell subpopulations in amoebic liver abscess. AB - BACKGROUND: Cellular immunity may play a major role in the pathogenesis of amoebic liver abscess but there is little data on the effect of treatment on T cell subpopulations in such patients. METHODS: We performed a prospective, controlled study of the T lymphocyte subpopulations in 17 patients with amoebic liver abscess before, and at 4 and 8 weeks after treatment with metronidazole (30 mg/kg/day). T4 and T8 cells were studied using monoclonal antibodies by the alkaline phosphatase anti-alkaline phosphatase staining technique. RESULTS: The mean T4 cell percentages in the acute stage of illness and at 4 and 8 weeks after treatment were 27, 26 and 27 respectively and the mean T8 cell percentages were 19, 24 and 29. The T4:T8 ratio at the acute stage was 1.7, and 1.1 and 1.2 at 4 and 8 weeks of therapy. The T4:T8 ratio at the acute stage did not differ significantly (p > 0.05) from that in the control group. However, at 4 and 8 weeks after therapy there was a significant increase (p < 0.05) in the T8 cells with no significant change in the T4 cells. CONCLUSION: We suggest that sensitization of the T8 cells occurs in patients with amoebic liver abscess in the later phase of the disease. This may be responsible for the elimination of the parasite from the human host. PMID- 1304306 TI - Population growth, development and family planning in India. PMID- 1304308 TI - St. John's Medical College, Bangalore. PMID- 1304309 TI - Hepatitis B virus DNA in PCR. PMID- 1304307 TI - Psychiatry in India. PMID- 1304310 TI - Continued use of Fahrenheit system in India. PMID- 1304311 TI - Vaccine stability in different environments, not at different temperatures. PMID- 1304312 TI - Devaluation of public teaching hospitals. PMID- 1304313 TI - Control of breathing by endogenous opioid peptides: possible involvement in sudden infant death syndrome. AB - Experiments have been performed in order to evaluate the respiratory consequences of a suppression or accumulation of endogenous opioid peptides, in the neuronal network which generates the motor respiratory activity. Iontophoretic application of naloxone onto respiratory neurons increases their firing activity and increases their respiratory modulation. On the other hand the local injection of kelatorphan (an enkephalinase inhibitor) decreases the firing of respiratory neurons and thus reduces the respiratory modulation. This effect of kelatorphan mimics the effect on respiratory neuron of an iontophoretic application of met enkephalin. Furthermore the local injection of kelatorphan reduces the frequency of the respiratory output recorded from the phrenic nerve. This effect is reversed by systemic administration of naloxone. The results demonstrate the involvement of endogenous opioid peptides in the control of breathing suggesting that in Sudden Infant Death Syndrome a possible dysregulation in opioidergic system could occur. PMID- 1304314 TI - In vitro study of newborn rat brain maturation: implication for sudden infant death syndrome. AB - We have used slice preparation from newborn rats to study the development of the nucleus tractus solitarius neuronal network and brain intracellular phosphorus metabolites. As shown previously on adults, the newborn preparation retains local excitatory and inhibitory synaptic connections and enables study of intrinsic electrical properties in the nucleus tractus solitarius. Electrophysiological investigation of inhibitory synaptic transmission demonstrated a maturational step at days 4-6 after birth. Nuclear magnetic resonance spectroscopy of brain slices revealed a metabolic maturation between postnatal days 11 and 17. Results emphasize the differential maturation steps during the postnatal development of rat central nervous system. Possibly, Sudden Infant Death Syndrome may result from the abnormal timing in the occurrence of these steps. PMID- 1304315 TI - Expression of recombinant human nerve growth factor in Escherichia coli. AB - Nerve growth factor (NGF) is a neurotrophic factor for basal forebrain cholinergic neurons and may be of benefit in neurodegenerative diseases of humans. A method is described to obtain significant amounts of biologically active recombinant human NGF (rhNGF) in one step. RhNGF was expressed in E. coli and the majority of the protein accumulated in inclusion bodies. It was immunoprecipitated by a serum against mouse NGF. Solubilization of the inclusion bodies was done in 3M guanidine HCl and renaturation was effected by dilution and air oxidation in the presence of 6 microM CuSO4. Recoveries were 10-12 micrograms of rhNGF per ml of bacterial suspension. Its biological activity was tested in a bioassay system employing sympathetic chick embryo ganglia and was inhibited by the monoclonal antibody 27/21 against mouse NGF. PMID- 1304316 TI - Regulatory mechanisms in melatonin biosynthesis in retina. AB - The vertebrate retina produces melatonin in a light-dependent rhythmic fashion, synchronized with, but independent from the rhythm of the hormone formation in the pineal gland. This review summarizes the current status of our knowledge on regulatory mechanisms involved in controlling the retinal melatonin biosynthesis. Special emphasis is given to the role and mode of action of dopamine and GABA, two established retinal neurotransmitters, as well as that of second messengers (cyclic AMP, calcium ions). Comparisons are made between lower vertebrates and mammals. PMID- 1304317 TI - Potent in vivo but not in vitro inhibition of monoamine oxidase by 3-chloro-alpha phenylpyrazinemethanol. AB - 3-Chloro-alpha-phenylpyrazinemethanol (3-CPM) inhibited monoamine oxidase (MAO) types A and B in vivo in mouse brain, heart and liver. The inhibition was dose dependent at doses of 0.3-32 mg/kg i.p. and occurred within 1 h after the compound was injected. 3-CPM was a very weak inhibitor of mouse brain mitochondrial MAO activity in vitro, even when preincubated with the enzyme; MAO A was inhibited only about 50% at a high concentration of 3-CPM (1 mM), and MAO-B was inhibited even less. After a 10 mg/kg i.p. dose of 3-CPM in mice, both MAO-A and MAO-B were inhibited at day 1, but activity had largely recovered within a few days in brain, liver and heart. 3-CPM at doses of 1, 3, 10 and 32 mg/kg i.p. caused dose-dependent antagonism of the depletion of striatal dopamine and of cortical norepinephrine by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 3-CPM is therefore a potent inhibitor of MAO-A and of MAO-B in mice in vivo despite its weak effect on the enzyme in vitro. A metabolite of the drug may be involved in the in vivo effects. PMID- 1304318 TI - Calcium dependent release of acetylcholine and gamma-aminobutyric acid from the rabbit retina. AB - The concurrent release of endogenous ACh and GABA from the retina (in the presence of physostigmine) was measured using either an eye-cup preparation in rabbits anaesthetized with urethane or isolated rabbit retinas. There was a spontaneous resting release of ACh and GABA from the dark adapted retina of ca 5 and 160 pmol min-1 respectively. Stimulation of the initially dark adapted retina in vivo with flickering light (0.1-20 Hz) increased the release of ACh by up to 5 times the spontaneous resting release but did not cause a detectable increase in GABA release. The maximum light-evoked release of ACh was about 24 pmol min 1/retina and occurred at a frequency of 10 Hz. However, the maximum release of ACh per flash occurred at 0.1 Hz at which frequency the average ACh release per flash from one amacrine cell was ca 2.35 x 10(-18) mol. Exposure of the retina to the potent inhibitors of GABA uptake, SKF89976A and SKF100330A markedly reduced the resting release of ACh and abolished the light-evoked release of ACh but did not enable a light-evoked release of GABA to be detected. Bicuculline blocked the inhibitory actions of both SKF89976A and SKF100330A on ACh release but the combination of bicuculline and uptake inhibitor did not result in a light-evoked release of GABA. In contrast, KCl (20 mM) applied locally to the retina in vivo resulted in the release of both ACh and GABA (61 and 2.6-fold respectively). KCl (20 mM) also evoked large increases in ACh and GABA release from isolated rabbit retinas in room light (13.5 and 3.4-fold respectively). The K-evoked release of ACh and GABA from the rabbit retina both in vivo and in vitro was calcium dependent. These experiments are the first in which endogenous ACh and GABA release from the retina have been simultaneously measured and suggest that the release mechanisms for these transmitters are fundamentally similar. PMID- 1304320 TI - Inhibition of evoked neurotransmitter release from rat hippocampus by a polypeptide toxin isolated from the marine snail Conus distans. AB - The active fraction, isolated and partially purified from the crude venom of the marine snail Conus distans, with a molecular mass of about 25 kDa, inhibits neurotransmitter release in rat hippocampus. This toxin (distans Toxin) inhibits the electrically evoked tritium labelled noradrenaline release from rat hippocampal slices in a dose and time dependent manner. The neurotransmitter release is mainly regulated by N-type of voltage sensitive Ca(2+)-channels. The distans toxin behaves as a partial antagonist of calcium in the buffer, possibly by competing with calcium for this type of voltage sensitive Ca(2+)-channels. PMID- 1304321 TI - Homocysteine-induced alterations in extracellular amino acids in rat hippocampus. AB - The effects of DL-homocysteine, and DL-homocysteate, on extracellular levels of amino acids in the rat hippocampus have been studied using brain microdialysis. Hippocampal electroencephalogram activity was monitored simultaneously using an electrode attached to the dialysis probe. DL-Homocysteine (1200 mg/kg; i.p. injection) produced epileptic activity in hippocampus in an inconsistent manner. Alterations in electroencephalogram activity were not observed in urethane anaesthetized animals, whereas 50% of Hypnorm anaesthetized animals exhibited epileptic activity. DL-Homocysteate (2 mu mol; i.c.v.) induced epileptic activity in a majority of animals anaesthetized using urethane. Dialysate levels of aspartate were significantly elevated by homocysteine in both groups of animals. Conversely, dialysis levels of GABA were reduced. Dialysate levels of other amino acids measured (glutamate, glutamine, taurine, alanine and valine) were not affected significantly. Dialysate levels of taurine were increased significantly in animals injected with homocysteate. These data suggest that the imbalance in excitatory:inhibitory neurotransmission in the hippocampus caused by these alterations in extracellular levels of neuroexcitatory (i.e. aspartate) and neuroinhibitory (i.e. GABA) transmitters could underly the epileptic effect of homocysteine. PMID- 1304319 TI - In vitro binding of isolated synaptic vesicles to presynaptic plasma membranes: activation by Ca2+ and protein kinase C. AB - An in vitro model to study the molecular control of binding of highly purified synaptic vesicles to presynaptic plasma membranes has been developed. Presynaptic plasma membranes were immobilized by dotting onto nitrocellulose, and binding of iodinated synaptic vesicle membranes was studied under varying experimental conditions. Synaptic vesicles bind to presynaptic plasma membranes in the presence of Ca2+ and ATP. Binding is reduced in the presence of EGTA and abolished by the calmodulin antagonist trifluoperazine. Vesicle binding is stimulated 5-fold after incubation--prior to dotting--of presynaptic plasma membranes with ATP in the presence of the phorbol-ester 12-O-tetradecanoylphorbol 13-acetate (1 microM) and 2.5-fold after preincubation with Ca2+ (50 microM). Pretreatment of plasma membranes with alkaline phosphatase strongly reduces vesicle binding. Microsomes prepared from bovine liver did not bind to presynaptic plasma membranes. Our results suggest that activation of protein kinase C and Ca2+ stimulate binding of synaptic vesicles to the presynaptic membrane. In the intact nerve terminal this interaction may represent an initial step in synaptic vesicle exocytosis. PMID- 1304322 TI - Increase in cortical and midbrain tryptophan hydroxylase activity by intracerebroventricular administration of corticotropin releasing factor: block by adrenalectomy, by RU 38486 and by bilateral lesions to the central nucleus of the amygdala. AB - Corticotropin releasing factor (CRF) infused bilaterally into the lateral ventricles of awake, chronically cannulated, male Sprague-Dawley rats produced a dose-dependent increase in the in vitro activity of cortical and midbrain tryptophan hydroxylase after 60 min. The maximal increase in enzyme activity of 60% over that of vehicle-treated controls was reached 45 min after an infusion of 3 micrograms CRF. The increase in enzyme activity after a single dose of CRF resembled that seen after exposure of rats to an acute sound stress: it was reversed by preincubation of the enzyme preparation with alkaline phosphatase and was nonadditive with the increase in activity obtained in the presence of phosphorylating conditions. The response to intracerebroventricularly administered CRF was abolished by bilateral adrenalectomy, but restored by repeated daily systemic administration of the synthetic glucocorticoid, dexamethasone (500 micrograms/day, i.p. for 3 days), to the adrenalectomized rats. Intracerebroventricular administration of the glucocorticoid antagonist, RU 38486 (200 micrograms/day for 4 days), also blocked the acute increase in tryptophan hydroxylase activity in response to CRF. Finally, bilateral lesions to the central nucleus of the amygdala, a region involved in mediating behavioral, endocrine and autonomic responses to stressful stimuli, abolished the increase in enzyme activity in response to intraventricular CRF. The glucocorticoid sensitivity of the response to CRF, as well as the involvement of the central nucleus of the amygdala support the view that CRF may have a role in mediating the enhancement of tryptophan hydroxylase activity by acute sound stress. PMID- 1304323 TI - Beta-endorphin: regional levels profile in the brain of the human infant. AB - Immunoradiometrical determinations of beta-endorphin (beta-EP) levels in 29 discrete brain regions from a series of victims of "Sudden Infant Death Syndrome" yielded a uniformly low levels profile in various areas of telencephalon, thalamus, pons, cerebellum and medulla oblongata. This low levels profile was interrupted by intermediate and high beta-EP levels in the midbrain and in two diencephalic zones. This study provides, for the first time, a comprehensive, neurochemically determined regional profile of beta-EP levels in the brain of the human infant. PMID- 1304325 TI - Rapid kinetics of depolarization-induced changes in intrasynaptosomal calcium concentrations. AB - The rapid kinetics of depolarization-evoked calcium influxes in isolated nerve terminals from rat cortex were monitored by stopped-flow spectrofluorimetry using specific indicators (Fluo-3, Indo-1). A very rapid increase in the intrasynaptosomal Ca(2+)-level was detected within the subsecond time range after depolarizing synaptosomes by mixing with physiological saline containing elevated K(+)-concentrations. About 15 mM [K+]o was determined as threshold concentration for inducing Ca(2+)-influx, which increased with higher concentration and saturated at [K+]o-concentrations of about 40 mM [K+]o. PMID- 1304324 TI - Beta-endorphin and neurotensin in brainstem and cerebrospinal fluid in the sudden infant death syndrome. AB - Beta-endorphin (BE) and neurotensin (NT) are two neuropeptides which induce apneas. In infants who died of Sudden Infant Death Syndrome (SIDS) we measured, in brainstem and CSF, BE and NT by IRMA and RIA respectively. BE and NT levels are compared to same aged infant and adult controls. CSF BE level was significantly higher in SIDS than in the two control groups (86 +/- 14 vs 33 +/- 13 and 16 +/- 5 pmol/l). In 6 SIDS victims NT and BE were assayed in 5 brainstem sections, each of them divided in median, intermediate and lateral parts. We found high levels of BE in every fragment (3-11 pmol/mg protein) while NT elevated values were restricted to the mesencephalic regions (1.4-12 pmol/mg), the medial pons (6 pmol/mg) and the intermediate parts of the medulla (including the olive: 1.3-1.6 pmol/mg). These results support the hypothesis that NT and/or BE could induce or participate to the fetal issue of SIDS. PMID- 1304326 TI - Inhibition of high affinity choline uptake in the rat brain by neurotoxins: effect of monosialoganglioside GM1. AB - Mustard derivatives of ethyl-choline and hemicholinium-3 have been suggested as possible specific cholinergic neurotoxins. In this study a structural analog of hemicholinium-3, a,a'-bis[di(2-chloroethyl)amino]-4,4'-2-biacetophenone (toxin 7), was added to synaptosomes prepared from the cortex, striatum or hippocampus of rat brain. Synaptosomal high affinity choline uptake (HACU) was significantly decreased in a dose-dependent manner by addition of toxin 7, while synaptosomal uptake of GABA or dopamine was not changed. Incubation of cortical synaptosomes with the monosialoganglioside GM1 prevented the decrease in HACU seen following administration of toxin 7. This preventative effect of GM1 was greater if GM1 was added prior to or concomitant with toxin 7, than if GM1 was added following toxin 7. Two newly synthesized hemicholinium-3 analogs, 4-[3'-di(2 chloroethyl)aminopropionyl]biphenyl (toxin 5) and 4-[3'-di(2 bromoethyl)aminopropionyl]biphenyl (toxin 6) caused a large decrease in HACU when added to cortical synaptosomes, this decrease was significantly greater than that seen with the same dose of toxin 7 or ethyl-choline aziridinium (AF64A). Ultrastructural changes in the synaptosomal membrane following incubation with toxin 7 or toxin 7 with GM1 were examined by electron microscopy. Development of a compound which is both a potent neurotoxin, and is specific for cholinergic neurons will allow new insights into the normal function of the cholinergic system in the CNS and provide animal models of disease states in which cholinergic degeneration is an important element. PMID- 1304327 TI - A minimal model to account for the response of N-Methyl-D-aspartate receptors expressed in Xenopus oocyte injected with rat brain mRNA. AB - N-Methyl-D-aspartate (NMDA) receptors were expressed in Xenopus oocytes by injecting rat brain mRNA. NMDA-elicited responses in the oocytes were measured by the voltage-clamping method. The following measurements were made in the presence of 50 microM glycine (Gly) to establish the relationship between the NMDA concentration and the current: (1) the NMDA-induced membrane current before desensitization; (2) the NMDA-induced membrane current after desensitization equilibrium; (3) the fraction of the active form of the receptor after desensitization equilibrium in the presence and absence of 50 microM Gly; (4) the rate of the recovery of desensitized receptors upon removal of NMDA. Gly was essential for not only the activation of NMDA receptors but also their desensitization. These results were analyzed on the basis of a minimal model where one agonist and one Gly binding site were assumed. The equilibrium and rate constants of the model were evaluated for NMDA in the presence of saturating amounts of Gly. This model will be useful for systematically explaining the complicated responses of NMDA receptors. PMID- 1304328 TI - Specific ganglioside-cell protein interactions: a study performed with GM1 ganglioside derivative containing photoactivable azide and rat cerebellar granule cells in culture. AB - The incubation of cultured rat cerebellar granule cells with a photoreactive derivative of radiolabeled GM1 ganglioside, [3H]GM1(N3), followed by illumination, led to the specific association of ganglioside to cell proteins. After 30 min of incubation only a few out of the cell proteins became radiolabeled. Two of these, at apparent molecular weights of 95 and 112 kDa, are interacting with the portion of associated ganglioside that is released by trypsin treatment; others, in the region between 31 and 44 kDa, are probably bound to molecules of ganglioside inserted into the outer membrane layer, thus showing that the ganglioside association to the cell surface is a selective phenomenon, involving specific proteins. Increasing the incubation time up to 24 h resulted in a larger number of radiolabeled proteins, probably as a consequence of the internalization and metabolic processing of administered [3H]GM1(N3). In fact, photoreactive and radioactive metabolic derivatives of [3H]GM1(N3) can also interact with a number of proteins. After 24 h incubation, some radioactivity was also associated to cytosolic proteins. Again in this case the interaction with proteins seems to be a specific process involving only a few out of the total cytosolic proteins. PMID- 1304329 TI - Gangliosides and neuronal differentiation. AB - Using the GD3-specific mAb R24 we demonstrate by immunohistochemistry that the first embryonic cells of chicken expressing GD3 represent heavily proliferating cells of mesodermal origin (mesenchymal stem and endothelial cells). At this developmental stage (E1-1.5) neuroectodermal cells of the forming neural tube are not stained by R24 or any other available anti-ganglioside antibodies. These cells of the neural tube start to express GD3 at around E1.5 in parallel with increasing proliferative activity. Likewise proliferating and migrating neuronal crest derivates as well as undifferentiated retinal cells, the forming lens and otic placodes increasingly express GD3 in an organ-specific pattern following the spatiotemporal increase in mitotic activity. Immunostaining of GD1b (mAb D21b) or c-pathway polysialogangliosides (mAb Q211) is not obtained before E2.5, is nervous tissue specific and restricted to "new-born" neurons, which start to migrate and form first neurites. This striking change in ganglioside synthesis and expression also occurs in primary cell cultures (after or without previous Q211-mediated complement kill of neurons) during differentiation of mitotic progenitor cells to neurons (neurogenesis). In cell culture, the fluorescence staining is evenly distributed over the whole neuronal surface including filopodia at the growth cones. Monensin (10(-8) M) prevents expression of GD1b and c-polysialogangliosides and simultaneously differentiation of neuronal morphology (neurogenesis). The presence of exogenous gangliosides from bovine brain leads to a decrease of the monensin effect or even abolishes it. PMID- 1304330 TI - Disposition of exogenous tritium-labelled GM1lactone in the rat. AB - The disposition of labelled [3H]GM1lactone, the inner ester of ganglioside GM1, was studied in the rat. After i.v. administration [3H]GM1lactone was quickly converted to its corresponding open form most likely by plasma esterases, and then displayed a pharmacokinetic profile identical to [3H]GM1. Following intramuscular administration of [3H]GM1lactone [3H]GM1 levels in plasma and in tissues were higher than those obtained after the administration of an equivalent dose of [3H]GM1. This increased bioavailability means that GM1lactone can be considered as a potential prodrug of GM1. PMID- 1304331 TI - Study of brain and vascular plexus gangliosides in meningoencephalitis of various etiology. AB - The content of brain and vascular plexus gangliosides and their composition have been studied in 15 cases of meningoencephalitis of various etiology and degree of disease. The most pronounced decrease of ganglioside concentration was found in brain of children, who died from herpes virus infection. Decrease of ganglioside content was revealed in brain grey matter of patients with influenza virus or meningococcus infection, but not in cases of mycoplasma infection. These data provide evidence of nerve cell destruction due to meningoencephalitis of various etiology. The biochemical data obtained are in good agreement with the results of the brain of children infection by herpes virus (increase of GD1b content in grey matter). Ganglioside content in vascular plexes of patients with meningoencephalitis was found to be, on the contrary, much higher (ca 4 times) than in the controls. The higher the lesion of choroid plexes in meningoencephalitis is, the higher the ganglioside content in them is. PMID- 1304332 TI - Gangliosides and regeneration of the goldfish optic nerve in vivo and in vitro. AB - One to forty days after optic nerve transection, goldfish received an i.p. injection of [3H]proline (proteins), 3HNAcGluc (gangliosides) or [3H]thymidine (DNA). After 1 or 2 days of incorporation, both optic systems were analyzed by biochemical and autoradiographical procedures. In the regenerating retina an enhanced retinal mitotic activity, protein synthesis (up to 2-fold) and ganglioside synthesis (up to 1.5-fold) was found. Simultaneously, a transiently enhanced accumulation (up to 4.5-fold) of axonally transported protein- and ganglioside-bound radioactivity in the regenerating optic nerve stump occurred. These regeneration-related proliferative and metabolic changes were found to be maximal at 6-8 days post lesion, but still measurable after 40 days. Concerning the endogenous ganglioside metabolism, in the regenerating retina no obvious change in ganglioside synthesis and composition could be observed, while in the regenerating optic nerve there was an enhanced accumulation of the ganglioside GP1c. Daily i.p. application of a ganglioside mixture from bovine brain (GMix) or of the monosialoganglioside GM1, did not alter significantly the degree and time course of the above regeneration induced metabolic changes or the regain of visual acuity. Sprouting activity of goldfish retinal explants was found to strongly depend upon a conditioning lesion of the optic nerve, reaching a maximum 8 days after nerve transection. This result strictly coincided with the profile of metabolic changes observed in vivo. Again, daily i.p. or i.o. injection of exogenous gangliosides did not influence the lesion induced increase of retinal sprouting activity. However, in normal, not regenerating animals, a local i.o. injection of GMix or GM1 led to a significant enhancement of the "basal" sprouting activity, normally occurring after lesion of the retina after injection of 0.9% NaCl. This ganglioside related stimulation was maximal at low concentrations (3 micrograms/eye) and did not occur at high concentrations (> 30 micrograms/eye). Injection of the phospholipid phosphatidylcholine or phosphatidylserine had no or a slightly inhibitory effect, when compared to NaCl controls. These data suggest an involvement of gangliosides in the complex process of induction of axonal sprouting. PMID- 1304333 TI - Lasting effects of postnatal hypoxia and saline injection on the striatal dopamine transport and their modification by gangliosides. AB - Hypobaric hypoxia (10 h daily, pO2 10 kPa) and saline administration (2.5 microliters/g body wt) from the 2nd till the 11th day of life both induced a long lasting increase of the low-affinity dopamine (DA) uptake capacity in S1 fractions of the rat striatum. Additionally, the potassium-stimulated DA release was enhanced in adult control rats postnatally injected with saline. The administration of a mixture of bovine brain gangliosides (30 micrograms/g body wt) was found to prevent these effects. However, the kinetic constants of the DA uptake of hypoxic rats treated with gangliosides were reduced in comparison to untreated controls. Thus, the effects of gangliosides appear to differ between hypoxic and control conditions. The modification of the dopaminergic activity during brain development is discussed as a possible mechanism of the preventive effects of gangliosides against long-term cerebral dysfunctions following hypoxia or stress. PMID- 1304334 TI - 24R,25-dihydroxyvitamin D3 prevents aluminum-induced alteration of brain gangliosides in uremic rats by keeping the metal within perivascular astrocytes of the blood-brain barrier. AB - The administration of aluminum (Al) to uremic rats leads to Al accumulation in different brain regions with subsequent alteration of brain gangliosides. Addition of 24R,25-dihydroxyvitamin D3[24R,25-(OH)2D3] did not influence the brain Al content determined by plasma argon emission spectrometry, but prevented the decrease in brain gangliosides. By using electron microscopy and laser microprobe mass analysis, it was demonstrated that in rats given 24R,25-(OH)2D3 together with Al, the metal was mainly kept within perivascular astrocytes of the blood-brain barrier. On the contrary, in rats given Al only, the metal was evenly distributed throughout the brain areas causing extensive demyelination, chromatolysis of nerve cells in some brain regions (hippocampus) and brain edema. Our results could find application in the prevention of Al-induced encephalopathy in patients on hemodialysis. PMID- 1304335 TI - Ganglioside-dependent factor, inhibiting lipid peroxidation in rat brain synaptosomes. AB - Preincubation of rat brain synaptosomes with GM1, GD1a or GT1b (10(-10)-10(-6) M), as well as with phorbol 12-myristate, 13-acetate (10(-10)-10(-6) M) was found to have dose dependent inhibitory effect on Fe(2+)-ascorbate induced lipid peroxidation, while penetrating analogue of c-AMP markedly decreased the inhibitory effect of these compounds. In liposomes made of lipids isolated from synaptosomal membranes the degree of inhibition of induced LPO by gangliosides was practically absent. The inhibitory effect of GM1 on lipid peroxidation could not be revealed after thermal denaturation of synaptosomes or after treatment with polymyxin B (inhibitor of lipid-dependent protein kinases). These results and some other data provide evidence for the existence of ganglioside-dependent factor inhibiting lipid peroxidation in brain tissue. It may be suggested to be a protein kinase modulated by gangliosides. PMID- 1304336 TI - Cell surface distribution of endogenous and effects of exogenous gangliosides on neuronal survival, cell shape and growth in vitro. AB - In vitro immunostaining of neurons from spinal cord or brain of embryonic chicken by means of monoclonal anti-ganglioside antibodies (Q211, D21b) revealed a fluorescence-labeling of c-polysialogangliosides and GD1b evenly distributed over the entire neuronal surface including filopodia at the growth cones. On electronmicroscopical level the gold-stained ganglioside-antigens were found more or less densely packed in small adjacent areas suggesting a concentration in local "domains". Survival in serum-free or serum-containing medium of embryonic spinal cord motoneurons, which normally died if not cultivated in muscle conditioned medium or in contact to myotubes, was remarkably improved in the presence of a ganglioside mixture (10 microM) from bovine brain. If embryonic neurons from optic lobes were cultivated at low Ca(2+)-concentration (< 20 microM) they developed flat, broad cell bodies with many filopodia and only a few flat-shaped short processes. A very weak cytoskeleton-staining by means of rhodamine-linked phalloidine indicated that polymerization of actin was impaired in these neurons. At the same low Ca(2+)-concentration of < 20 microM but in the presence of ganglioside GM1 (up to 100 microM) most of the neurons developed a "normal" cell shape with rounded perikarya and thin neurites with "normal" shaped growth cones. In this case rhodamine-linked phalloidine revealed a much more intense staining mainly concentrated within the growing tips. The morphology and growth of the ganglioside-treated neurons resembled that of neurons cultivated at a higher Ca(2+)-concentration of at least 600 microM. PMID- 1304337 TI - Gangliosides in the human brain development and aging. AB - In this study, brain gangliosides in prenatal and postnatal human life were analyzed. Immunohistochemically, the presence of "c"-pathway of gangliosides (GQ1c) in embryonic brain was only recorded at 5 weeks of gestation. Biochemical results indicated a twofold increase in human cortex ganglioside concentration between 16 and 22 weeks of gestation. The increasing ganglioside concentration was based on an increasing GD1a ganglioside fraction in all regions analyzed except cerebellar cortex, which was characterized by increasing GT1b. In this developmental period, GD3 was found to be localized in the ventricular zone of the cortical wall. After birth, GD1b ganglioside in neuropil of granular cell layer corresponding to growing mossy fibers was expressed in cerebellar cortex. Between birth and 20/30 years of age, a cerebral neocortical difference of ganglioside composition was observed, characterized by lowest GD1a in visual cortex. Analyzing the composition of gangliosides in cortical regions during aging, they were observed to follow region-specific alterations. In frontal cortex, there was a greater decrease in GD1a and GM1 than in GT1b and GD1b, but in occipital (visual) cortex there was no change in individual gangliosides. In hippocampus, GD1a moderately decreased, whereas other fractions were stable. In cerebellar cortex, GD1b and GT1b fractions decreased with aging. PMID- 1304338 TI - Cortical distribution of gangliosides in Alzheimer's disease. AB - In Alzheimer's disease, all ganglio-series gangliosides (GM1, GD1a, GD1b and GT1b) were found to be decreased in temporal and frontal cortex, and nucleus basalis of Meynert. In addition, in Alzheimer's disease simple gangliosides (GM2, GM3) were elevated in frontal and parietal cortex, possibly correlating to accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death. PMID- 1304339 TI - NMR structure of oxidized Escherichia coli glutaredoxin: comparison with reduced E. coli glutaredoxin and functionally related proteins. AB - The determination of the NMR structure of oxidized Escherichia coli glutaredoxin in aqueous solution is described, and comparisons of this structure with that of reduced E. coli glutaredoxin and the related proteins E. coli thioredoxin and T4 glutaredoxin are presented. Based on nearly complete sequence-specific 1H-NMR assignments, 804 nuclear Overhauser enhancement distance constraints and 74 dihedral angle constraints were obtained as the input for the structure calculations, for which the distance geometry program DIANA was used followed by simulated annealing with the program X-PLOR. The molecular architecture of oxidized glutaredoxin is made up of three helices and a four-stranded beta-sheet. The three-dimensional structures of oxidized and the recently described reduced glutaredoxin are very similar. Quantitative analysis of the exchange rates of 34 slowly exchanging amide protons from corresponding series of two-dimensional [15N,1H]-correlated spectra of oxidized and reduced glutaredoxin showed close agreement, indicating almost identical hydrogen-bonding patterns. Nonetheless, differences in local dynamics involving residues near the active site and the C terminal alpha-helix were clearly manifested. Comparison of the structure of E. coli glutaredoxin with those of T4 glutaredoxin and E. coli thioredoxin showed that all three proteins have a similar overall polypeptide fold. An area of the protein surface at the active site containing Arg 8, Cys 11, Pro 12, Tyr 13, Ile 38, Thr 58, Val 59, Pro 60, Gly 71, Tyr 72, and Thr 73 is proposed as a possible site for interaction with other proteins, in particular ribonucleotide reductase. It was found that this area corresponds to previously proposed interaction sites in T4 glutaredoxin and E. coli thioredoxin. The solvent-accessible surface area at the active site of E. coli glutaredoxin showed a general trend to increase upon reduction. Only the sulfhydryl group of Cys 11 is exposed to the solvent, whereas that of Cys 14 is buried and solvent inaccessible. PMID- 1304341 TI - Lysine-21 of Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase participates in substrate binding through charge-charge interaction. AB - Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase (G6PD) was isolated in high yield and purified to homogeneity from a newly constructed strain of Escherichia coli which lacks its own glucose 6-phosphate dehydrogenase gene. Lys 21 is one of two lysyl residues in the enzyme previously modified by the affinity labels pyridoxal 5'-phosphate and pyridoxal 5'-diphosphate-5'-adenosine, which are competitive inhibitors of the enzyme with respect to glucose 6-phosphate (LaDine, J.R., Carlow, D., Lee, W.T., Cross, R.L., Flynn, T.G., & Levy, H.R., 1991, J. Biol. Chem. 266, 5558-5562). K21R and K21Q mutants of the enzyme were purified to homogeneity and characterized kinetically to determine the function of Lys-21. Both mutant enzymes showed increased Km-values for glucose 6-phosphate compared to wild-type enzyme: 1.4-fold (NAD-linked reaction) and 2.1-fold (NADP linked reaction) for the K21R enzyme, and 36-fold (NAD-linked reaction) and 53 fold (NADP-linked reaction) for the K21Q enzyme. The Km for NADP+ was unchanged in both mutant enzymes. The Km for NAD+ was increased 1.5- and 3.2-fold, compared to the wild-type enzyme, in the K21R and K21Q enzymes, respectively. For the K21R enzyme the kcat for the NAD- and NADP-linked reactions was unchanged. The kcat for the K21Q enzyme was increased in the NAD-linked reaction by 26% and decreased by 30% in the NADP-linked reaction from the values for the wild-type enzyme. The data are consistent with Lys-21 participating in the binding of the phosphate group of the substrate to the enzyme via charge-charge interaction. PMID- 1304340 TI - Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases. AB - We report the X-ray analysis at 2.0 A resolution for crystals of the aspartic proteinase endothiapepsin (EC 3.4.23.6) complexed with a potent difluorostatone containing tripeptide renin inhibitor (CP-81,282). The scissile bond surrogate, an electrophilic ketone, is hydrated in the complex. The pro-(R) (statine-like) hydroxyl of the tetrahedral carbonyl hydrate is hydrogen-bonded to both active site aspartates 32 and 215 in the position occupied by a water in the native enzyme. The second hydroxyl oxygen of the hydrate is hydrogen-bonded only to the outer oxygen of Asp 32. These experimental data provide a basis for a model of the tetrahedral intermediate in aspartic proteinase-mediated cleavage of the amide bond. This indicates a mechanism in which Asp 32 is the proton donor and Asp 215 carboxylate polarizes a bound water for nucleophilic attack. The mechanism involves a carboxylate (Asp 32) that is stabilized by extensive hydrogen bonding, rather than an oxyanion derivative of the peptide as in serine proteinase catalysis. PMID- 1304342 TI - Beta beta homodimers exist in native rabbit skeletal muscle tropomyosin and increase after denaturation-renaturation. AB - Native tropomyosin from rabbit skeletal muscle (RSTm) consists mainly of alpha alpha and alpha beta coiled coils (alpha/beta approximately 3-4/1). In some extant studies, no beta beta molecules have been found. In this study, RSTm from several different preparations was disulfide cross-linked, both preparation and cross-linking being done under nondenaturing conditions. The cross-linked product was assayed for the presence of beta beta molecules cross-linked at both C36 and C190 (beta = beta). In such cross-linked RSTm, 3-8% beta = beta is detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis, C4 reversed-phase high performance liquid chromatography, and a free-solution capillary electrophoresis experiment. This percentage becomes approximately 4-10% beta beta when corrected for incomplete double cross-linking and is independent of protein concentration (0.1-10.0 mg/mL), indicating that the observed beta beta species are not artifacts due to intermolecular cross-linking. Upon denaturation and subsequent renaturation either by heating to 55 degrees C or by incubating at 45 degrees C followed by quenching to room temperature, or by guanidine hydrochloride exposure followed by phased renaturation by dialysis, the fraction of beta beta increases, indicating that the reassociation favors homodimer formation somewhat over random association. This result differs from the random association observed when the sulfhydryl on one of the chains is carboxyamidomethylated (Holtzer, M.E., Breiner, T., & Holtzer, A., 1984, Biopolymers 23, 1811-1833), and from the overwhelming heterodimer preferences reported for tropomyosins from other organisms (Lehrer, S.S., Qian, Y., & Hvidt, S., 1989, Science 246, 926-928; Lehrer, S.S. & Qian, Y., 1990, J. Biol. Chem. 265, 1134-1138). PMID- 1304343 TI - A functional protein hybrid between the glucose transporter and the N acetylglucosamine transporter of Escherichia coli. AB - The glucose and N-acetylglucosamine-specific transporters (IIGlc/IIIGlc and IIGlcNAc) of the bacterial phosphotransferase system mediate carbohydrate uptake across the cytoplasmic membrane concomitant with substrate phosphorylation. The two transporters have 40% amino acid sequence identity. Eight chimeric proteins between the two transporters were made by gene reconstruction. All hybrid proteins could be expressed, some inhibited cell growth, and one was active. The active hybrid transporter consists of the transmembrane domain (residues 1-386) of the IIGlc subunit and the two hydrophilic domains (residues 370-648) of IIGlcNAc. The N-terminal hydrophilic domain of IIGlcNAc contains the transiently phosphorylated cysteine-412. The hybrid protein is specific for glucose, which indicates that the sugar specificity determinant is in the transmembrane domain and that the cysteine from which the phosphoryl group is transferred to the substrate is not part of the binding site. The protein sequence (LKTPGRED) at which the successful fusion occurred has the characteristic properties of an interdomain oligopeptide linker (Argos, P., 1990, J. Mol. Biol. 211, 943-958). PMID- 1304344 TI - Mast cell tryptases: examination of unusual characteristics by multiple sequence alignment and molecular modeling. AB - Tryptases are trypsin-like serine proteinases found in the granules of mast cells. Although they show 40% sequence identity with trypsin and contain only 20 or 21 additional residues, tryptases display several unusual features. Unlike trypsin, the tryptases only make limited cleavages in a few proteins and are not inhibited by natural trypsin inhibitors, they form tetramers, bind heparin, and their activity on synthetic substrates is progressively inhibited as the concentration of salt increases above 0.2 M. Unique sequence features of seven tryptases were identified by comparison to other serine proteinases. The three dimensional structures of the tryptases were then predicted by molecular modeling based on the crystal structure of bovine trypsin. The models show two large insertions to lie on either side of the active-site cleft, suggesting an explanation for the limited activity of tryptases on protein substrates and the lack of inhibition by natural inhibitors. A group of conserved Trp residues and a unique proline-rich region make two surface hydrophobic patches that may account for the formation of tetramers and/or inhibition with increasing salt. Although they contain no consensus heparin-binding sequence, the tryptases have 10-13 more His residues than trypsin, and these are positioned on the surface of the model. In addition, clustering of Arg and Lys residues may also contribute to heparin binding. Putative Asn-linked glycosylation sites are found on the opposite side of the model from the active site. The model provides structural explanations for some to the unusual characteristics of the tryptases and a rational basis for future experiments, such as site-directed mutagenesis. PMID- 1304345 TI - Quantitative analysis of cyclic beta-turn models. AB - The beta-turn is a frequently found structural unit in the conformation of globular proteins. Although the circular dichroism (CD) spectra of the alpha helix and beta-pleated sheet are well defined, there remains some ambiguity concerning the pure component CD spectra of the different types of beta-turns. Recently, it has been reported (Hollosi, M., Kover, K.E., Holly, S., Radics, L., & Fasman, G.D., 1987, Biopolymers 26, 1527-1572; Perczel, A., Hollosi, M., Foxman, B.M., & Fasman, G.D., 1991a, J. Am. Chem. Soc. 113, 9772-9784) that some pseudohexapeptides (e.g., the cyclo[(delta)Ava-Gly-Pro-Aaa-Gly] where Aaa = Ser, Ser(OtBu), or Gly) in many solvents adopt a conformational mixture of type I and the type II beta-turns, although the X-ray-determined conformation was an ideal type I beta-turn. In addition to these pseudohexapeptides, conformational analysis was also carried out on three pseudotetrapeptides and three pseudooctapeptides. The target of the conformation analysis reported herein was to determine whether the ring stress of the above beta-turn models has an influence on their conformational properties. Quantitative nuclear Overhauser effect (NOE) measurements yielded interproton distances. The conformational average distances so obtained were interpreted utilizing molecular dynamics (MD) simulations to yield the conformational percentages. These conformational ratios were correlated with the conformational weights obtained by quantitative CD analysis of the same compounds. The pure component CD curves of type I and type II beta-turns were also obtained, using a recently developed algorithm (Perczel, A., Tusnady, G., Hollosi, M., & Fasman, G.D., 1991b, Protein Eng. 4(6), 669-679). For the first time the results of a CD deconvolution, based on the CD spectra of 14 beta-turn models, were assigned by quantitative NOE results. The NOE experiments confirmed the ratios of the component curves found for the two major beta-turns by CD analysis. These results can now be used to enhance the conformational determination of globular proteins on the basis of their CD spectra. PMID- 1304346 TI - Inclusion of solvation free energy with molecular mechanics energy: alanyl dipeptide as a test case. AB - A combined force field of molecular mechanics and solvation free energy is tested by carrying out energy minimization and molecular dynamics on several conformations of the alanyl dipeptide. Our results are qualitatively consistent with previous experimental and computational studies, in that the addition of solvation energy stabilizes the C5 conformation of the alanyl dipeptide relative to the C7. PMID- 1304347 TI - An optimization approach to predicting protein structural class from amino acid composition. AB - Proteins are generally classified into four structural classes: all-alpha proteins, all-beta proteins, alpha + beta proteins, and alpha/beta proteins. In this article, a protein is expressed as a vector of 20-dimensional space, in which its 20 components are defined by the composition of its 20 amino acids. Based on this, a new method, the so-called maximum component coefficient method, is proposed for predicting the structural class of a protein according to its amino acid composition. In comparison with the existing methods, the new method yields a higher general accuracy of prediction. Especially for the all-alpha proteins, the rate of correct prediction obtained by the new method is much higher than that by any of the existing methods. For instance, for the 19 all alpha proteins investigated previously by P.Y. Chou, the rate of correct prediction by means of his method was 84.2%, but the correct rate when predicted with the new method would be 100%! Furthermore, the new method is characterized by an explicable physical picture. This is reflected by the process in which the vector representing a protein to be predicted is decomposed into four component vectors, each of which corresponds to one of the norms of the four protein structural classes. PMID- 1304348 TI - Selection of representative protein data sets. AB - The Protein Data Bank currently contains about 600 data sets of three-dimensional protein coordinates determined by X-ray crystallography or NMR. There is considerable redundancy in the data base, as many protein pairs are identical or very similar in sequence. However, statistical analyses of protein sequence structure relations require nonredundant data. We have developed two algorithms to extract from the data base representative sets of protein chains with maximum coverage and minimum redundancy. The first algorithm focuses on optimizing a particular property of the selected proteins and works by successive selection of proteins from an ordered list and exclusion of all neighbors of each selected protein. The other algorithm aims at maximizing the size of the selected set and works by successive thinning out of clusters of similar proteins. Both algorithms are generally applicable to other data bases in which criteria of similarity can be defined and relate to problems in graph theory. The largest nonredundant set extracted from the current release of the Protein Data Bank has 155 protein chains. In this set, no two proteins have sequence similarity higher than a certain cutoff (30% identical residues for aligned subsequences longer than 80 residues), yet all structurally unique protein families are represented. Periodically updated lists of representative data sets are available by electronic mail from the file server "netserv@embl-heidelberg.de." The selection may be useful in statistical approaches to protein folding as well as in the analysis and documentation of the known spectrum of three-dimensional protein structures. PMID- 1304351 TI - Design, synthesis, and characterization of a protein sequencing reagent yielding amino acid derivatives with enhanced detectability by mass spectrometry. AB - We report the design, chemical synthesis, and structural and functional characterization of a novel reagent for protein sequence analysis by the Edman degradation, yielding amino acid derivatives rapidly detectable at high sensitivity by ion-evaporation mass spectrometry. We demonstrate that the reagent 3-[4'(ethylene-N,N,N-trimethylamino)phenyl]-2-isothiocyanate is chemically stable and shows coupling and cyclization/cleavage yields comparable to phenylisothiocyanate, the standard reagent in chemical sequence analysis, under conditions typically encountered in manual or automated sequence analysis. Amino acid derivatives generated with this reagent were detectable by ion-evaporation mass spectrometry at the subfemtomole sensitivity level at a pace of one sample per minute. Furthermore, derivatives were identified by their mass, thus permitting the rapid and highly sensitive determination of the molecular nature of modified amino acids. Derivatives of amino acids with acidic, basic, polar, or hydrophobic side chains were reproducibly detectable at comparable sensitivities. The polar nature of the reagent required covalent immobilization of polypeptides prior to automated sequence analysis. This reagent, used in automated sequence analysis, has the potential for overcoming the limitations in sensitivity, speed, and the ability to characterize modified amino acid residues inherent in the chemical sequencing methods that are currently used. PMID- 1304350 TI - The molecular mechanism for the tetrameric association of glycogen phosphorylase promoted by protein phosphorylation. AB - The allosteric transition of glycogen phosphorylase promoted by protein phosphorylation is accompanied by the association of a pair of functional dimers to form a tetramer. The conformational changes within the dimer that lead to the creation of a protein recognition surface have been analyzed from a comparison of the crystal structures of T-state dimeric phosphorylase b and R-state tetrameric phosphorylase a. Regions of the structure that participate in the tetramer interface are situated within structural subdomains. These include the glycogen storage subdomain, the C-terminal subdomain and the tower helix. The subdomains undergo concerted conformational transitions on conversion from the T to the R state (overall r.m.s. shifts between 1 and 1.7 A) and, together with the quaternary conformational change within the functional dimer, create the tetramer interface. The glycogen storage subdomain and the C-terminal subdomain are distinct from those regions that contribute to the dimer interface, but shifts in the subdomains are correlated with the allosteric transitions that are mediated by the dimer interface. The structural properties of the tetramer interface are atypical of an oligomeric protein interface and are more similar to protein recognition surfaces observed in protease inhibitors and antibody-protein antigen complexes. There is a preponderance of polar and charged residues at the tetramer interface and a high number of H-bonds per surface area (one H-bond per 130 A2). In addition, the surface area made inaccessible at the interface is relatively small (1,142 A2 per subunit on dimer to tetramer association compared with 2,217 A2 per subunit on monomer-to-dimer association). PMID- 1304352 TI - Structural analysis of wild-type and mutant yeast calmodulins by limited proteolysis and electrospray ionization mass spectrometry. AB - Calmodulin from Saccharomyces cerevisiae was expressed in Escherichia coli and purified. The purified protein was structurally characterized using limited proteolysis followed by ESI mass spectrometry to identify the fragments. In the presence of Ca2+, yeast calmodulin is sequentially cleaved at arginine 126, then lysine 115, and finally at lysine 77. The rapid cleavage at Arg-126 suggests that the fourth Ca(2+)-binding loop does not bind Ca2+. In the presence of EGTA, yeast calmodulin is more susceptible to proteolysis and is preferentially cleaved at Lys-106. In addition, mutant proteins carrying I100N, E104V or both mutations, which together confer temperature sensitivity to yeast, were characterized. The mutant proteins are more susceptible than wild-type calmodulin to proteolysis, suggesting that each mutation disrupts the structure of calmodulin. Furthermore, whereas wild-type calmodulin is cut at Lys-106 only in the presence of EGTA, this cleavage site is accessible in the mutants in the presence of Ca2+ as well. In these ways, the structural consequence of each mutation mimics the loss of a calcium ion in the third loop. In addition, although wild-type calmodulin binds to four proteins in a yeast crude extract in the presence of Ca2+, the mutants bind only to a subset of these. Thus, the inability to adopt the stable Ca(2+) bound conformation in the third Ca(2+)-binding loop alters the ability of calmodulin to interact with yeast proteins in a Ca(2+)-dependent manner. PMID- 1304353 TI - Guanidine derivatives restore activity to carboxypeptidase lacking arginine-127. AB - Arg-127 stabilizes the oxyanion of the tetrahedral intermediate formed during Zn2+ carboxypeptidase A-catalyzed hydrolysis. Mutant carboxypeptidases lacking Arg-127 exhibit substantially reduced rates of hydrolysis with the change manifest almost entirely in kcat (kcat/Km is decreased by 10(4) for R127A). Therefore, Arg-127 stabilizes the enzyme-transition state complex but not the ground state enzyme-substrate complex (Phillips, M.A., Fletterick, R., & Rutter, W.J., 1990, J. Biol. Chem. 265, 20692-20698). The addition of guandine, methylguanidine, or ethylguanidine to R127A increases the kcat for hydrolysis of Bz-gly(o)phe by 10(2) without changing the Km. Dissociation constants (Kd) for the guanidine derivatives range from 0.1 to 0.5 M. The binding affinity for the transition state analog Cbz-phe-alaP(o)ala is increased similarly by 10(2); in contrast, the binding affinity of the ground state inhibitor benzylsuccinic acid is not altered. Thus, guanidine derivatives mimic Arg-127 in stabilizing the rate limiting transition state. Hydrolysis of Bz-gly-(o)phe by wild-type carboxypeptidase, R127K, or R127M is not substantially affected by guanidine derivatives. Additionally, primary amines do not change the activity of R127A. These observations imply that guanidine binds in the cavity vacated by Arg-127 specifically and in a productive conformation for catalysis. PMID- 1304349 TI - The refined 1.9-A X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. AB - Thrombin is a multifunctional serine proteinase that plays a key role in coagulation while exhibiting several other key cellular bioregulatory functions. The X-ray crystal structure of human alpha-thrombin was determined in its complex with the specific thrombin inhibitor D-Phe-Pro-Arg chloromethylketone (PPACK) using Patterson search methods and a search model derived from trypsinlike proteinases of known spatial structure (Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S.R., & Hofsteenge, J., 1989, EMBO J. 8, 3467-3475). The crystallographic refinement of the PPACK-thrombin model has now been completed at an R value of 0.156 (8 to 1.92 A); in particular, the amino- and the carboxy termini of the thrombin A-chain are now defined and all side-chain atoms localized; only proline 37 was found to be in a cis-peptidyl conformation. The thrombin B-chain exhibits the characteristic polypeptide fold of trypsinlike serine proteinases; 195 residues occupy topologically equivalent positions with residues in bovine trypsin and 190 with those in bovine chymotrypsin with a root mean-square (r.m.s.) deviation of 0.8 A for their alpha-carbon atoms. Most of the inserted residues constitute novel surface loops. A chymotrypsinogen numbering is suggested for thrombin based on the topological equivalences. The thrombin A chain is arranged in a boomeranglike shape against the B-chain globule opposite to the active site; it resembles somewhat the propeptide of chymotrypsin(ogen) and is similarly not involved in substrate and inhibitor binding. Thrombin possesses an exceptionally large proportion of charged residues. The negatively and positively charged residues are not distributed uniformly over the whole molecule, but are clustered to form a sandwichlike electrostatic potential; in particular, two extended patches of mainly positively charged residues occur close to the carboxy-terminal B-chain helix (forming the presumed heparin-binding site) and on the surface of loop segment 70-80 (the fibrin[ogen] secondary binding exosite), respectively; the negatively charged residues are more clustered in the ringlike region between both poles, particularly around the active site. Several of the charged residues are involved in salt bridges; most are on the surface, but 10 charged protein groups form completely buried salt bridges and clusters. These electrostatic interactions play a particularly important role in the intrachain stabilization of the A-chain, in the coherence between the A- and the B-chain, and in the surface structure of the fibrin(ogen) secondary binding exosite (loop segment 67-80).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1304354 TI - Dissociation of peripheral protein-membrane complexes by high pressure. AB - The ability of high pressure to dissociate several peripheral protein-membrane complexes was investigated. Three vitamin K-dependent proteins (factor X, protein Z, and prothrombin) dissociated from small unilamellar vesicles (SUVs, 30 nm diameter) composed of 25% phosphatidylserine (PS) and 75% phosphatidylcholine (PC) at comparable pressures (midpoints of 0.3-0.6 kbar). The pressure-induced dissociation curves for the factor X-SUV interaction followed the expected behavior for an interaction with an apparent dissociation equilibrium constant at atmospheric pressure, KD(atm), of 9 x 10(-7) M and a change in volume of association, delta Va, of 88 mL/mol. Factor X also dissociated from large unilamellar vesicles (LUVs, 100 nm diameter, 25% PS:75% PC) with a midpoint of 0.5 kbar. A second group of calcium-dependent membrane-binding proteins included protein kinase C (PKC), a 64-kDa protein, and a 32-kDa protein. The 32-kDa protein dissociated from SUVs (midpoint of 0.8 kbar), whereas PKC and the 64-kDa protein did not dissociate to a significant degree. The differences in dissociability of these proteins appeared to be a result of the differences in their KD(atm)'s (decreased dissociability with decreased KD(atm)). This pattern was further demonstrated by the relatively high midpoint of dissociation (1.1-1.4 kbar) of serum amyloid P component (SAP; KD(atm) ca. 10(-11)) and the limited dissociation of factor Va light chain (KD(atm) ca. 10(-11)). Changing the vesicle composition to phosphatidylethanolamine in place of PC gave higher affinity and decreased dissociation of the 32-kDa protein and SAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304355 TI - Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution-state structure of the nucleocapsid protein from HIV-1. AB - All retroviral nucleocapsid (NC) proteins contain one or two copies of an invariant 3Cys-1His array (CCHC = C-X2-C-X4-H-X4-C; C = Cys, H = His, X = variable amino acid) that are essential for RNA genome packaging and infectivity and have been proposed to function as zinc-binding domains. Although the arrays are capable of binding zinc in vitro, the physiological relevance of zinc coordination has not been firmly established. We have obtained zinc-edge extended X-ray absorption fine structure (EXAFS) spectra for intact retroviruses in order to determine if virus-bound zinc, which is present in quantities nearly stoichiometric with the CCHC arrays (Bess, J.W., Jr., Powell, P.J., Issaq, H.J., Schumack, L.J., Grimes, M.K., Henderson, L.E., & Arthur, L.O., 1992, J. Virol. 66, 840-847), exists in a unique coordination environment. The viral EXAFS spectra obtained are remarkably similar to the spectrum of a model CCHC zinc finger peptide with known 3Cys-1His zinc coordination structure. This finding, combined with other biochemical results, indicates that the majority of the viral zinc is coordinated to the NC CCHC arrays in mature retroviruses. Based on these findings, we have extended our NMR studies of the HIV-1 NC protein and have determined its three-dimensional solution-state structure. The CCHC arrays of HIV 1 NC exist as independently folded, noninteracting domains on a flexible polypeptide chain, with conservatively substituted aromatic residues forming hydrophobic patches on the zinc finger surfaces. These residues are essential for RNA genome recognition, and fluorescence measurements indicate that at least one residue (Trp37) participates directly in binding to nucleic acids in vitro. The NC is only the third HIV-1 protein to be structurally characterized, and the combined EXAFS, structural, and nucleic acid-binding results provide a basis for the rational design of new NC-targeted antiviral agents and vaccines for the control of AIDS. PMID- 1304357 TI - Specificity determinants of acylaminoacyl-peptide hydrolase. AB - In an attempt to explore how specific features of the substrate's primary structure may affect the activity of rabbit muscle acylaminoacyl-peptide hydrolase (EC 3.4.19.1), a number of acetylated peptides containing specific amino acid replacements in specific positions were prepared and compared as substrates for the hydrolase. The principal variants were D-Ala, Pro, and positive charges (His, Arg, Lys); in addition, the effect of the length of the peptide was also investigated in a less systematic manner. The substrates were either prepared by direct acetylation of peptides, by extension of the N-terminus with acetylamino acids or acetylpeptides, activated as N-hydroxysuccinimide esters, or by isolation of the N-terminal peptides from naturally occurring acetylated proteins. It was found that D-Ala on either side of the bond to be cleaved (positions 1 and 2) completely inhibited the enzymatic activity, whereas acetylated peptides with D-Ala in positions 3 or 4 were as good substrates as those containing L-Ala. Peptides with Pro in positions 2 were also inactive, and most of the peptides with Pro in the third position were very poor substrates; only the peptide Ac-AAP gave reasonably high activity (30% of Ac-AAA), which was reduced to 1-2% if additional residues were present at the C-terminus (Ac-AAPA, Ac-AAPAA). The presence of a positive charge in positions 2, 3, 4, 5, and 6 gave strong reduction in hydrolase activity varying with the charge's distance from the N-terminus from 0 to 15-20% of the rates obtained with the reference peptides without positive charges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304356 TI - Amino acid binding by the class I aminoacyl-tRNA synthetases: role for a conserved proline in the signature sequence. AB - Although partial or complete three-dimensional structures are known for three Class I aminoacyl-tRNA synthetases, the amino acid-binding sites in these proteins remain poorly characterized. To explore the methionine binding site of Escherichia coli methionyl-tRNA synthetase, we chose to study a specific, randomly generated methionine auxotroph that contains a mutant methionyl-tRNA synthetase whose defect is manifested in an elevated Km for methionine (Barker, D.G., Ebel, J.-P., Jakes, R.C., & Bruton, C.J., 1982, Eur. J. Biochem. 127, 449 457), and employed the polymerase chain reaction to sequence this mutant synthetase directly. We identified a Pro 14 to Ser replacement (P14S), which accounts for a greater than 300-fold elevation in Km for methionine and has little effect on either the Km for ATP or the kcat of the amino acid activation reaction. This mutation destabilizes the protein in vivo, which may partly account for the observed auxotrophy. The altered proline is found in the "signature sequence" of the Class I synthetases and is conserved. This sequence motif is 1 of 2 found in the 10 Class I aminoacyl-tRNA synthetases and, in the known structures, it is in the nucleotide-binding fold as part of a loop between the end of a beta-strand and the start of an alpha-helix. The phenotype of the mutant and the stability and affinity for methionine of the wild-type and mutant enzymes are influenced by the amino acid that is 25 residues beyond the C terminus of the signature sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304358 TI - Amino acid sequence of fibrolase, a direct-acting fibrinolytic enzyme from Agkistrodon contortrix contortrix venom. AB - The complete amino acid sequence of fibrolase, a fibrinolytic enzyme from southern copperhead (Agkistrodon contortrix contortrix) venom, has been determined. This is the first report of the sequence of a direct-acting, nonhemorrhagic fibrinolytic enzyme found in snake venom. The majority of the sequence was established by automated Edman degradation of overlapping peptides generated by a variety of selective cleavage procedures. The amino-terminus is blocked by a cyclized glutamine (pyroglutamic acid) residue, and the sequence of this region of the molecule was determined by mass spectrometry. Fibrolase is composed of 203 residues in a single polypeptide chain with a molecular weight of 22,891, as determined by the sequence. Its sequence is homologous to the sequence of the hemorrhagic toxin Ht-d of Crotalus atrox venom and with the sequences of two metalloproteinases from Trimeresurus flavoviridis venom. Microheterogeneity in the sequence was found at both the amino-terminus and at residues 189 and 192. All six cysteine residues in fibrolase are involved in disulfide bonds. A disulfide bond between cysteine-118 and cysteine-198 has been established and bonds between cysteines-158/165 and between cysteines-160/192 are inferred from the homology to Ht-d. Secondary structure prediction reveals a very low percentage of alpha-helix (4%), but much greater beta-structure (39.5%). Analysis of the sequence reveals the absence of asparagine-linked glycosylation sites defined by the consensus sequence: asparagine-X-serine/threonine. PMID- 1304360 TI - Mutation of conserved residues in Escherichia coli thioredoxin: effects on stability and function. AB - Mutations were made in three highly conserved residues in Escherichia coli thioredoxin. An internal charged residue, Asp-26, was changed to an alanine. The mutant protein was more stable than the wild type. It can function as a substrate for thioredoxin reductase with a 10-fold increase in the Km over the wild type. Although the redox potential was not substantially changed from that of the wild type, thioredoxin D26A was a poor reducing agent for ribonucleotide reductase. Asp-26 apparently serves to maintain an optimal charge distribution in the active site region for interaction with other proteins. Mutation of a surface Pro-34 in the active site disulfide ring to a serine had little effect on protein stability. A slight decrease in the redox potential (9 mV) made thioredoxin P34S a better reducing agent for ribonucleotide reductase. In contrast, mutation of the internal cis Pro-76 to an alanine destabilized the protein. The data indicate a change had also occurred in the charge distribution in the active site region. Thioredoxin P76A had a higher redox potential than the wild type protein and was not an effective reducing agent for ribonucleotide reductase. It was concluded that this residue is essential for maintaining the conformation of the active site and the redox potential of thioredoxin. PMID- 1304359 TI - Identification of the posttranslational modifications of bovine lens alpha B crystallins by mass spectrometry. AB - A combination of mass spectrometric techniques has been used to investigate the amino acid sequence and post-translational modifications of alpha B-crystallin isolated from bovine lenses by gel filtration chromatography and reversed-phase high performance liquid chromatography. Chromatographic fractions were analyzed by electrospray ionization mass spectrometry to determine the homogeneity and molecular weights of proteins in the fractions. The alpha B-crystallin primary gene product, its mono- and diphosphorylated forms, its N- and C-terminal truncated forms, as well as other lens proteins unrelated to the alpha B crystallins were identified by their molecular weights. Detailed information about the sites of phosphorylation, as well as evidence supporting reassignment of Asn to Asp at position 80, was obtained by analyzing proteolytic digests of these proteins by fast atom bombardment mass spectrometry. Results of this investigation indicate that alpha B-crystallin is phosphorylated in vivo at Ser 45, Ser 59, and either Ser 19 or 21. From the specificity of phosphorylation of alpha-crystallins, it appears that there may be two different kinases responsible for their phosphorylation. PMID- 1304361 TI - Optical activity associated with the sulfur to metal charge transfer bands of Zn and Cd GAL4. AB - The N-terminal DNA-binding domain of the GAL4 transcription factor, isolated as a proteolytic fragment of 63 amino acid residues, GAL4(63), or cloned as a 62 residue subdomain, GAL4(62*), binds 2 Cd(II) ions. Both Cd derivatives show intense ellipticity bands associated with -S(-)-->Cd charge transfer bands at 250 nm (+), 233 nm (-), and 218 nm (+). Molar ellipticity values are (5-7) x 10(4) deg.cm2.dmol-1. The energies and pattern (+,-,+) of these ellipticity bands are similar to those observed for the Cd(II) clusters of metallothionein. The latter are believed to be due to the presence of bridging cysteine ligands (Willner, H.W., Vasak, M., & Kagi, J.H.R., 1987, Biochemistry 26, 6287-6292). Circular dichroism provides further evidence that the GAL4 DNA-binding domain forms a binuclear Cd cluster with the amino acid sequence -C11-X2-C14-X6-C21-X6-C28-X2 C31-X6-C38- found in GAL4(62*). Zn2GAL4(62*) has much weaker ellipticity associated with the higher energy -S(-)--> Zn charge transfer bands. Removal of the metal ions from GAL4(62*) results in substantial changes in the near UV circular dichroism due to both loss of the charge transfer bands and changes in the conformation of the peptide backbone. Binding of the UASG enhancer DNA element to either Zn or Cd GAL4(62*) alters the ellipticity of the -S(-)--> metal charge transfer bands suggesting that DNA binding is associated with some changes in conformation around the metal cluster. PMID- 1304362 TI - Assembly of polypeptide and protein backbone conformations from low energy ensembles of short fragments: development of strategies and construction of models for myoglobin, lysozyme, and thymosin beta 4. AB - Recently we developed methods for the construction of knowledge-based mean fields from a data base of known protein structures. As shown previously, this approach can be used to calculate ensembles of probable conformations for short fragments of polypeptide chains. Here we develop procedures for the assembly of short fragments to complete three-dimensional models of polypeptide chains. The amino acid sequence of a given protein is decomposed into all possible overlapping fragments of a given length, and an ensemble of probable conformations is calculated for each fragment. The fragments are assembled to a complete model by choosing appropriate conformations from the individual ensembles and by averaging over equivalent angles. Finally a consistent model is obtained by rebuilding the conformation from the average angles. From the average angles the local variability of the structure can be calculated, which is a useful criterion for the reliability of the model. The procedure is applied to the calculation of the local backbone conformations of myoglobin and lysozyme whose structures have been solved by X-ray analysis and thymosin beta 4, a polypeptide of 43 amino acid residues whose structure was recently investigated by NMR spectroscopy. We demonstrate that substantial fractions of the calculated local backbone conformations are similar to the experimentally determined structures. PMID- 1304363 TI - Thermodynamics of melittin tetramerization determined by circular dichroism and implications for protein folding. AB - The tetramerization of melittin, a 26-amino acid peptide from Apis mellifera bee venom, has been studied as a model for protein folding. Melittin converts from a monomeric random coil to an alpha-helical tetramer as the pH is raised from 4.0 to 9.5, as ionic strength is increased, as temperature is raised or lowered from about 37 degrees C, or as phosphate is added. The thermodynamics of this tetramerization (termed "folding") are explored using circular dichroism. The melittin tetramer has two pKa values of 7.5 and 8.5 corresponding to protonation of the N-terminus and Lys 23, respectively. pKa values calculated with the program DelPhi (Gilson, M.K., Sharp, K.A., & Honig, B.H., 1987, J. Comp. Chem. 9, 327-335; Gilson, M.K. & Honig, B.H., 1988a, Proteins 3, 32-52; Gilson, M.K. & Honig, B.H., 1988b, Proteins 4, 7-18) agree with experimental titration data. Greater electrostatic repulsion of these protonated groups destabilizes the tetramer by 3.6 kcal/mol at pH 4.0 compared to pH 9.5. Increasing the concentration of NaCl in the solution from 0 to 0.5 M stabilizes the tetramer by 5-6 kcal/mol at pH 4.0. The effect of NaCl is modeled with a ligand-binding approach. The melittin tetramer is found to have a temperature of maximum stability ranging from 35.5 to 43 degrees C depending on the pH, unfolding above and below that temperature. delta Cp0 for folding ranges from -0.085 to -0.102 cal g-1 K-1, comparable to that of other small globular proteins (Privalov, P.L., 1979, Adv. Protein Chem. 33, 167-241). delta H0 and delta S0 are found to decrease with temperature, presumably due to the hydrophobic effect (Kauzmann, W., 1959, Adv. Protein Chem. 14, 1-63). Phosphate is found to perturb the equilibrium substantially with a maximal effect at 150 mM, stabilizing the tetramer at pH 7.4 and 25 degrees C by 4.6 kcal/mol. The enthalpy change due to addition of phosphate (-7.5 kcal/mol at 25 degrees C) can be accounted for by simple dielectric screening. Both circular dichroism and crystallographic results suggest that phosphate may bind Lys 23 at the ends of the elongated tetramer. These detailed measurements give insight into the relative importance of various forces for the stability of melittin in the folded form and may provide an experimental standard for future tests of computational energetics on this simple protein system. PMID- 1304364 TI - Reversible unfolding and refolding behavior of a monomeric aldolase from Staphylococcus aureus. AB - Thermal and GdmCl-induced unfolding transitions of aldolase from Staphylococcus aureus are reversible under a variety of solvent conditions. Analysis of the transitions reveals that no partially folded intermediates can be detected under equilibrium conditions. The stability of the enzyme is very low with a delta G0 value of -9 +/- 2 kJ/mol at 20 degrees C. The kinetics of unfolding and refolding of aldolase are complex and comprise at least one fast and two slow reactions. This complexity arises from prolyl isomerization reactions in the unfolded chain, which are kinetically coupled to the actual folding reaction. Comparison with model calculations shows that at least two prolyl peptide bonds give rise to the observed slow folding reactions of aldolase and that all of the involved bonds are presumably in the trans conformation in the native state. The rate constant of the actual folding reaction is fast with a relaxation time of about 15 s at the midpoint of the folding transition at 15 degrees C. The data presented on the folding and stability of aldolase are comparable to the properties of much smaller proteins. This might be connected with the simple and highly repetitive tertiary structure pattern of the enzyme, which belongs to the group of alpha/beta barrel proteins. PMID- 1304365 TI - Protein classification artificial neural system. AB - A neural network classification method is developed as an alternative approach to the large database search/organization problem. The system, termed Protein Classification Artificial Neural System (ProCANS), has been implemented on a Cray supercomputer for rapid superfamily classification of unknown proteins based on the information content of the neural interconnections. The system employs an n gram hashing function that is similar to the k-tuple method for sequence encoding. A collection of modular back-propagation networks is used to store the large amount of sequence patterns. The system has been trained and tested with the first 2,148 of the 8,309 entries of the annotated Protein Identification Resource protein sequence database (release 29). The entries included the electron transfer proteins and the six enzyme groups (oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases), with a total of 620 superfamilies. After a total training time of seven Cray central processing unit (CPU) hours, the system has reached a predictive accuracy of 90%. The classification is fast (i.e., 0.1 Cray CPU second per sequence), as it only involves a forward-feeding through the networks. The classification time on a full-scale system embedded with all known superfamilies is estimated to be within 1 CPU second. Although the training time will grow linearly with the number of entries, the classification time is expected to remain low even if there is a 10 100-fold increase of sequence entries. The neural database, which consists of a set of weight matrices of the networks, together with the ProCANS software, can be ported to other computers and made available to the genome community. The rapid and accurate superfamily classification would be valuable to the organization of protein sequence databases and to the gene recognition in large sequencing projects. PMID- 1304366 TI - Cysteinyl peptides labeled by dibromobutanedione in reaction with rabbit muscle pyruvate kinase. AB - The bifunctional reagent 1,4-dibromobutanedione (DBBD) reacts covalently with pyruvate kinase from rabbit muscle to cause inactivation of the enzyme at a rate that is linearly dependent on the reagent concentration, giving a second order rate constant of 444 min-1 M-1. The individual substrates phosphoenolpyruvate (with KCl), ADP, or ATP in the presence of divalent metal cation provide marked protection against inactivation suggesting that reaction occurs in the region of the active site. The limited incorporation of DBBD into pyruvate kinase was measured by reduction of the carbonyl groups of the enzyme-bound reagent using [3H]NaBH4. When pyruvate kinase was reacted with 120 microM DBBD at pH 7.0 for 50 min in the absence of protectants, 1.8 mol of tritium/mol of subunit was incorporated, whereas in the presence of phosphoenolpyruvate with KCl, only 1.0 mol of tritium was incorporated per mole of subunit. Modified peptides were isolated from tryptic digests of pyruvate kinase. Reaction of enzyme in the presence of substrate (showing no activity loss) yielded a single peptide, Asn Ile-X1-Lys, where X1 corresponds to Cys164 of the known amino acid sequence of muscle pyruvate kinase. In the absence of protectants, reaction for 10 min (when the enzyme retained substantial activity) yielded Asn-Ile-X1-Lys as the major labeled peptide, whereas reaction for 50 min (when the enzyme was 88% inactivated) yielded predominantly Asn-Ile-X1-Lys cross-linked to X2-Asp-Glu-Asn Ile-Leu-Trp-Leu-Asp-Tyr-Lys, where X2 corresponds to Cys151. Because activity loss correlates with the appearance of the cross-linked peptides but not with formation of Asn-Ile-X1-Lys, inactivation is likely caused by the reaction leading to the cross-link between Cys151 and Cys164. The distance between the alpha-carbons of these residues in the crystal structure is 15.5 A, whereas only 12.0 A can be spanned by the two side chains linked by a dioxobutyl group, suggesting either that pyruvate kinase undergoes a conformational change in forming the cross-link or that local rapid fluctuations in structure occur in solution to the extent of 3.5 A in this region of pyruvate kinase. PMID- 1304367 TI - Human platelet-derived endothelial cell growth factor is homologous to Escherichia coli thymidine phosphorylase. PMID- 1304368 TI - Contribution of physical chemistry to an understanding of protein structure and function. PMID- 1304369 TI - Structural and functional analyses of the repressor, RbsR, of the ribose operon of Escherichia coli. AB - The DNA sequence encoding the rbs repressor protein, RbsR, has been determined. Amino acid sequence analyses of the product of an rbsR-lacZ fusion and of affinity-purified RbsR demonstrate that translation begins at an unusual codon, TTG, and that the initial amino acid is removed during maturation of the protein. DNA-binding assays indicate that RbsR binds to a region of perfect dyad symmetry spanning the rbs operon transcriptional start site and that the affinity for the rbs operator is reduced by addition of ribose, consistent with ribose being the inducer of the operon. RbsR is a member of a family of homologous repressor proteins having very similar DNA-binding sites and binding to similar operator sequences. PMID- 1304370 TI - Structural homology between rbs repressor and ribose binding protein implies functional similarity. AB - The deduced amino acid sequence of the rbs repressor, RbsR, of Escherichia coli is homologous over its C-terminal 272 residues to the entire sequence of the periplasmic ribose binding protein. RbsR is also homologous to a family of bacterial repressor proteins including LacI. This implies that the structure of the repressor consists of a two-domain binding protein portion attached to a DNA binding domain having the four-helix structure of the LacI headpiece. The implications of these relationships to the mechanism of this class of repressors are discussed. PMID- 1304371 TI - Functional interactions of ligand cofactors with Escherichia coli transcription termination factor rho. I. Binding of ATP. AB - Escherichia coli transcription termination factor rho is an RNA-dependent ATPase, and ATPase activity is required for all its functions. We have characterized the binding of ATP to the physiologically relevant hexameric association state of rho in the absence of RNA and have shown that there are six ATP binding sites per rho hexamer. This stoichiometry has been verified by a number of different techniques, including ultracentrifugation, ultrafiltration, and fluorescence titration studies. We have also shown that ATP can bind to isolated monomers of rho when the hexamer is dissociated with the mild denaturant myristyltrimethylammonium bromide, demonstrating that each promoter of rho carries an ATP binding site. The six binding sites that we observe in the rho hexamer are not equivalent; the hexamer contains three strong (Ka approximately 3 x 10(6) M-1) and three weak (Ka approximately 10(5) M-1) binding sites for ATP. The binding constant of the weak binding site is just the reciprocal of the enzymatic Km for ATP as a substrate; thus these weak sites, as well as the strong sites, can, in principle, take part in the catalytic cycle. The asymmetry induced (or manifested) by ATP binding reduces the symmetry of the rho hexamer from a D3 to a pseudo-D3 state. This "breakage" of symmetry has implications for the molecular mechanism of rho, because an asymmetric structure can lead to directional helicase activity by invoking directionally distinct RNA binding and release reactions (see Geiselmann, J., Yager, T.D., & von Hippel, P.H., 1992c, Protein Sci. 1, 861-873). PMID- 1304372 TI - Purification of glutathionylspermidine and trypanothione synthetases from Crithidia fasciculata. AB - Two enzymes involved in the biosynthesis of the trypanosomatid-specific dithiol trypanothione-glutathionylspermidine (Gsp) synthetase and trypanothione (TSH) synthetase--have been identified and purified individually from Crithidia fasciculata. The Gsp synthetase has been purified 93-fold and the TSH synthetase 52-fold to apparent homogeneity from a single DEAE fraction that contained both activities. This constitutes the first indication that the enzymatic conversion of two glutathione molecules and one spermidine to the N1,N8 bis(glutathionyl)spermidine (TSH) occurs in two discrete enzymatic steps. Gsp synthetase, which has a kcat of 600/min, shows no detectable TSH synthetase activity, whereas TSH synthetase does not make any detectable Gsp and has a kcat of 75/min. The 90-kDa Gsp synthetase and 82-kDa TSH synthetase are separable on phenyl Superose and remain separated on gel filtration columns in high salt (0.8 M NaCl). Active complexes can be formed under low to moderate salt conditions (0.0-0.15 M NaCl), consistent with a functional complex in vivo. PMID- 1304373 TI - Identification of the guanine binding domain peptide of the GTP-binding site of glucagon. AB - Glucagon, a peptide hormone synthesized and secreted by alpha islet cells, regulates glucose homeostasis by several mechanisms. Using [gamma 32P]8N3GTP, a proven photoaffinity probe for GTP, a specific nucleotide binding site on human glucagon was detected that showed preference for GTP. Half-maximal saturation of photoinsertion into the polypeptide hormone was at 8-12 microM with either [alpha 32P]8N3GTP or [gamma 32P]8N3GTP. GTP protected photolabeling with an apparent kd of 15 microM, whereas ATP was less effective as a protector, exhibiting an apparent kd of about 30 microM. Maximal protection by GTP and ATP was over 90%. UTP, CTP, GDP, ADP, GMP, AMP, guanosine, adenosine, guanine, and adenine were much less effective protectors, indicating that binding is specific for purine nucleoside triphosphates, particularly GTP. Mg2+ at 150 microM enhanced photoinsertion (twofold), whereas at 2-10 mM, it inhibited photoinsertion. Both Ca2+ and Zn2+ at 0.2 mM decreased photoinsertion about 45%. Purification of chymotryptic and tryptic digests of photolabeled glucagon by reverse-phase high performance liquid chromatography (HPLC) revealed that the N-terminal peptide, HSQGTF, was the only peptide region covalently photomodified by [32P]8N3GTP. GTP, if present during photolysis, greatly reduced both photoinsertion into glucagon and the amount of radiolabeled peptide recovered on HPLC. The specificity of binding to the N-terminal region is suggestive of a physiological role for a glucagon-GTP complex in the mechanism of action of this hormone. PMID- 1304374 TI - Charge balance in the alpha-hydroxyacid dehydrogenase vacuole: an acid test. AB - The proposal that the active site vacuole of NAD(+)-S-lactate dehydrogenase is unable to accommodate any imbalance in electrostatic charge was tested by genetically manipulating the cDNA coding for human muscle lactate dehydrogenase to make a protein with an aspartic acid introduced at position 140 instead of the wild-type asparagine. The Asn 140-Asp mutant enzyme has the same kcat as the wild type (Asn 140) at low pH (4.5), and at higher pH the Km for pyruvate increases 10 fold for each unit increase in pH up to pH 9. We conclude that the anion of Asp 140 is completely inactive and that it binds pyruvate with a Km that is over 1,000 times that of the Km of the neutral, protonated aspartic-140. Experimental results and molecular modeling studies indicate the pKa of the active site histidine-195 in the enzyme-NADH complex is raised to greater than 10 by the presence of the anion at position 140. Energy minimization and molecular dynamics studies over 36 ps suggest that the anion at position 140 promotes the opening of and the entry of mobile solvent beneath the polypeptide loop (98-110), which normally seals off the internal active site vacuole from external bulk solvent. PMID- 1304375 TI - Complete enzymatic deglycosylation of native sex steroid-binding protein (SBP or SHBG) of human and rabbit plasma: effect on the steroid-binding activity. AB - An enzymatic procedure for the complete removal of the N-linked and O-linked oligosaccharide side chains of the sex steroid-binding proteins (SBP or SHBG) of human and rabbit plasma under native conditions is described. Deglycosylation was catalyzed by N-glycanase, neuraminidase, and O-glycanase and was monitored by SDS PAGE, lectin blotting, and molecular weight analyses by electrospray mass spectrometry. Digestion of rabbit SBP with N-glycanase generated a major 39,777 Da protein and two minor ones of 39,389 and 39,545 Da. The molecular weight of the major protein agrees with the molecular weight calculated from the sequence of the sugar-free polypeptide monomer (39,769 Da: Griffin, P.R., Kumar, S., Shabanowitz, J., Charbonneau, H., Namkung, P.C., Walsh, K.A., Hunt, D.F., & Petra, P.H., 1989, J. Biol. Chem. 264, 19066-19075), whereas the other two are deglycosylated proteolytic cleavage products lacking the TQR and TQ sequences at the amino-terminus. The N- and O-linked side chains of human SBP were removed by sequential digestion with N-glycanase and neuraminidase/O-glycanase. A 38,771-Da protein was generated, which agrees well with the molecular weight of the sugar free polypeptide monomer (Walsh, K.A., Titani, K., Kumar, S., Hayes, R., & Petra, P.H., 1986, Biochemistry 25, 7584-7590). N-deglycosylation of human and rabbit SBP has no effect on the steroid-binding activity, but removal of the O-linked side chains of N-deglycosylated human SBP results in an apparent 50% loss of steroid-binding activity and an increase in the Kd for the binding of 5 alpha dihydrotestosterone from 0.3 mM to 0.9 nM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304376 TI - Cis proline mutants of ribonuclease A. II. Elimination of the slow-folding forms by mutation. AB - Ribonuclease A is known to form an equilibrium mixture of fast-folding (UF) and slow-folding (US) species. Rapid unfolding to UF is then followed by a reaction in the unfolded state, which produces a mixture of UF, USII, USI, and possibly also minor populations of other US species. The two cis proline residues, P93 and P114, are logical candidates for producing the major US species after unfolding, by slow cis <==> trans isomerization. Much work has been done in the past on testing this proposal, but the results have been controversial. Site-directed mutagenesis is used here. Four single mutants, P93A, P93S, P114A, and P114G, and also the double mutant P93A, P114G have been made and tested for the formation of US species after unfolding. The single mutants P114G and P114A still show slow isomerization reactions after unfolding that produce US species; thus, Pro 114 is not required for the formation of at least one of the major US species of ribonuclease A. Both the refolding kinetics and the isomerization kinetics after unfolding of the Pro 93 single mutants are unexpectedly complex, possibly because the substituted amino acid forms a cis peptide bond, which should undergo cis --> trans isomerization after unfolding. The kinetics of peptide bond isomerization are not understood at present and the Pro 93 single mutants cannot be used yet to investigate the role of Pro 93 in forming the US species of ribonuclease A. The double mutant P93A, P114G shows single exponential kinetics measured by CD, and it shows no evidence of isomerization after unfolding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304377 TI - Role of interchain alpha-helical hydrophobic interactions in Ca2+ affinity, formation, and stability of a two-site domain in troponin C. AB - We have previously shown that a 34-residue synthetic peptide representing the calcium-binding site III of troponin C formed a symmetric two-site dimer consisting of two helix-loop-helix motifs arranged in a head-to-tail fashion (Shaw, G.S., Hodges, R.S., & Sykes, B.D., 1990, Science 249, 280-283). In this study the hydrophobicities of the alpha-helices were altered by replacing L-98 and F-102 in the N-terminal region and/or I-121 and L-122 in the C-terminal region with alanine residues. Our results showed that substitution of hydrophobic residues either in the N- or C-terminal region have little effect on alpha-helix formation but resulted in a 100- and 300-fold decrease in Ca2+ affinity, respectively. Simultaneous substitution of both hydrophobes in the N- and C terminal region resulted in a 1,000-fold decrease in Ca2+ affinity. Data from guanidine hydrochloride denaturation studies suggested that intermolecular interactions occur and that the less hydrophobic analogs had a lower overall conformational stability. These data support the contention that the hydrophobic residues are important in the formation of the two-site domain in troponin C, and this hydrophobic association stabilizes Ca2+ affinity. PMID- 1304378 TI - X-ray grade crystals of a designed alpha-helical coiled coil. PMID- 1304379 TI - Mapping of the catalytic site of CHO-t-PA and the t-PA variant BM 06.022 by synthetic inhibitors and substrates. AB - BM 06.022 is a t-PA deletion variant that is produced as inactive inclusion bodies in Escherichia coli and transformed into the native form by an in vitro refolding process. Until now, no X-ray and NMR structures of BM 06.022 were available. Therefore a detailed kinetic analysis of the hydrolysis of peptide substrates and of the inhibition by several benzamidine-derived inhibitors was carried out in order to assess that the active site region of the protease domain of BM 06.022 is correctly structured in comparison with t-PA. Our data reveal that the single-chain as well as the two-chain form of BM 06.022 and native t-PA are similar in catalytic and in inhibitor binding properties. This indicates that the active site and the highly complex rearrangement of t-PA upon cleavage of the Arg275-Ile276 bond are maintained in BM 06.022. PMID- 1304380 TI - The accessibility of etheno-nucleotides to collisional quenchers and the nucleotide cleft in G- and F-actin. AB - Recent publication of the atomic structure of G-actin (Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., & Holmes, K. C., 1990, Nature 347, 37-44) raises questions about how the conformation of actin changes upon its polymerization. In this work, the effects of various quenchers of etheno-nucleotides bound to G- and F-actin were examined in order to assess polymerization-related changes in the nucleotide phosphate site. The Mg(2+)-induced polymerization of actin quenched the fluorescence of the etheno-nucleotides by approximately 20% simultaneously with the increase in light scattering by actin. A conformational change at the nucleotide binding site was also indicated by greater accessibility of F-actin than G-actin to positively, negatively, and neutrally charged collisional quenchers. The difference in accessibility between G- and F-actin was greatest for I-, indicating that the environment of the etheno group is more positively charged in the polymerized form of actin. Based on calculations of the change in electric potential of the environment of the etheno group, specific polymerization-related movements of charged residues in the atomic structure of G actin are suggested. The binding of S-1 to epsilon-ATP-G-actin increased the accessibility of the etheno group to I- even over that in Mg(2+)-polymerized actin. The quenching of the etheno group by nitromethane was, however, unaffected by the binding of S-1 to actin. Thus, the binding of S-1 induces conformational changes in the cleft region of actin that are different from those caused by Mg2+ polymerization of actin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304381 TI - Spectroscopic and chemical studies of the interaction between nerve growth factor (NGF) and the extracellular domain of the low affinity NGF receptor. AB - Nerve growth factor (NGF) interacts with a cell surface receptor on responsive neurons to initiate a series of cellular events leading to neuronal survival and/or differentiation. The first step in this process is the binding of NGF to a low affinity and/or a high affinity receptor. In the present report, we have studied the conformation and stability of recombinant receptor extracellular domain (RED) from the human low affinity receptor and the structural basis of its interaction with NGF. Circular dichroism (CD) studies indicate that the RED is primarily random coil in nature with little regular secondary structure. Thermal stability studies have shown that this irregular conformation is a specific structure that can undergo a reversible two-state thermal denaturation with a concomitant fluorescent and CD change. During heating at 100 degrees C for 15 min, the structure of RED is sufficiently unfolded for a reducing agent, dithiothreitol, to inactivate the receptor toward NGF binding and cross-linking. The complex formation between the RED and NGF has been examined by differential CD measurements, and we have shown that a small, reproducible change in conformation occurs in RED or NGF upon interaction. These results are interpreted in terms of the initiation of NGF cell surface binding and possible modes of signal transduction. PMID- 1304382 TI - Intramolecular interactions in pancreatic ribonucleases. AB - A detailed analysis of the composition and properties of hydrophobic nuclei and microclusters in pancreatic ribonuclease A (RNase A) has been carried out. Distance calculations for all noncovalently bonded atoms revealed that the average number of nonpolar contacts between a side chain of an amino acid and its neighbors is substantially larger if it involves hydrophobic residues rather than nonhydrophobic ones. However, the difference decreased when the number of contacts per nonpolar group and/or atom were calculated. Three main nuclei and five microclusters were identified, and their quantitative parameters were calculated. These nuclei include hydrophobic residues with a substantial number of nonpolar contacts with the environment (Phe 8, Phe 120, Phe 46, Tyr 25, Tyr 97, Ile 107, Leu 35, Ile 81, Val 54, Val 108, Met 29, Met 30). Hydrophobic nuclei of RNase A differ in shape and in composition, in the number of intranuclear contacts and of associated residues, as well as in their internal mobility. All eight cysteine residues are involved in nonpolar interactions with amino acid residues of hydrophobic nuclei. Active site amino acid residues of RNase A form a noncovalent contact network comprised of themselves, as well as of many conserved residues from hydrophobic nuclei. Sequence alignment with some other members of the RNase A family of proteins shows remarkable similarity in positions and in conservation of the main nonpolar residues, comprising cores of two (out of three) hydrophobic nuclei. A correlation was shown to exist between the average density of contacts for side-chain atoms and the number of amino acids to be found in the appropriate positions in the sequences of related mammalian ribonucleases. However, there are certain amino acid positions in the third, smaller nucleus, which are highly variable within the family. Taking into account that this nucleus is composed of residues belonging to different elements of the secondary structure, it is likely that the mutual orientation of these elements can be somehow different for these proteins. PMID- 1304383 TI - Crystal structure of a complex of HIV-1 protease with a dihydroxyethylene containing inhibitor: comparisons with molecular modeling. AB - The structure of a crystal complex of recombinant human immunodeficiency virus type 1 (HIV-1) protease with a peptide-mimetic inhibitor containing a dihydroxyethylene isostere insert replacing the scissile bond has been determined. The inhibitor is Noa-His-Hch psi [CH(OH)CH(OH)]Vam-Ile-Amp (U-75875), and its Ki for inhibition of the HIV-1 protease is < 1.0 nM (Noa = 1 naphthoxyacetyl, Hch = a hydroxy-modified form of cyclohexylalanine, Vam = a hydroxy-modified form of valine, Amp = 2-pyridylmethylamine). The structure of the complex has been refined to a crystallographic R factor of 0.169 at 2.0 A resolution by using restrained least-squares procedures. Root mean square deviations from ideality are 0.02 A and 2.4 degrees, for bond lengths and angles, respectively. The bound inhibitor diastereomer has the R configurations at both of the hydroxyl chiral carbon atoms. One of the diol hydroxyl groups is positioned such that it forms hydrogen bonds with both the active site aspartates, whereas the other interacts with only one of them. Comparison of this X-ray structure with a model-built structure of the inhibitor, published earlier, reveals similar positioning of the backbone atoms and of the side-chain atoms in the P2-P2' region, where the interaction with the protein is strongest. However, the X-ray structure and the model differ considerably in the location of the P3 and P3' end groups, and also in the positioning of the second of the two central hydroxyl groups. Reconstruction of the central portion of the model revealed the source of the hydroxyl discrepancy, which, when corrected, provided a P1-P1' geometry very close to that seen in the X-ray structure. PMID- 1304384 TI - Overexpression, purification, and characterization of yeast cyclophilins A and B. AB - Two isoforms of yeast cyclophilins, yCyPA and yCyPB, have been subcloned, expressed in Escherichia coli, and purified to homogeneity. The full-length (163 amino acid) yeast CyPA was easily expressed and purified; however, only a genetically truncated, 186-residue form of yCyPB lacking a putative 20-amino acid signal sequence could be purified. Each yeast cyclophilin isoform is a peptidyl prolyl isomerase, inhibitable by the immunosuppressive drug CsA (IC50's of 40 +/- 8 nM and 101 +/- 14 nM at 18 nM concentrations of yCyPA and yCyPB, respectively). Polyclonal antibodies raised against recombinant yCyPA detected native yCyPA in yeast cell extracts by both immunoprecipitation and Western blot analysis. However, polyclonal antibodies raised against recombinant yCyPB detected no native yCyPB in yeast cell extracts by Western blot analysis; small amounts of yCyPB were found in the culture broth, suggesting secretion extracellularly of this isoform. Northern analysis indicated that both yCyPA mRNA and yCYPB mRNA (at a much lower level) were detectable in cell-free extracts. Characterization of the yeast cyclophilin proteins demonstrated that their catalytic properties and sensitivity to CsA parallel those of the human cyclophilins. PMID- 1304385 TI - 83-kilodalton heat shock proteins of trypanosomes are potent peptide-stimulated ATPases. AB - A Crithidia fasciculata 83-kDa protein purified during a separate study of C. fasciculata trypanothione synthetase was shown to have ATPase activity and to belong to the hsp90 family of stress proteins. Because no ATPase activity has previously been reported for the hsp90 class, ATP utilization by C. fasciculata hsp83 was characterized: this hsp83 has an ATPase kcat of 150 min-1 and a Km of 60 microM, whereas the homologous mammalian hsp90 binds ATP but has no ATPase activity. Crithidia fasciculata hsp83 undergoes autophosphorylation on serine and threonine at a rate constant of 3.3 x 10(-3) min-1. Similar analysis was performed on recombinant Trypanosoma cruzi hsp83, and comparable ATPase parameters were obtained (kcat = 100 min-1, Km = 80 microM, kautophosphorylation = 6.3 x 10(-3) min-1). The phosphoenzyme is neither on the ATPase hydrolytic pathway nor does it affect ATPase catalytic efficiency. Both C. fasciculata and T. cruzi hsp83 show up to fivefold stimulation of ATPase activity by peptides of 6-24 amino acids. PMID- 1304386 TI - Inhibitory effects of HSP70 chaperones on nascent polypeptides. AB - Several of the major heat shock proteins (HSPs) function normally as molecular chaperones to prevent aggregation of immature polypeptides and thereby facilitate folding and oligomerization. To determine their effect on nascent polypeptides, we added purified preparations of different isoforms of HSP70 to in vitro translation reactions primed by the 26S mRNA of Sindbis virus, which encodes an autoprotease that functions cotranslationally, or by the mRNA encoding the yeast vacuolar H+ATPase, which is formed by a novel transpeptidase activity that removes the central region of the initial polypeptide. In the presence of HSP70s both the autoprotease and transpeptidase activities were inhibited, indicating that these chaperones can interact with nascent polypeptides and, in the cases studied here, perturb their normal structures. PMID- 1304388 TI - Sequence analysis of peptide mixtures by automated integration of Edman and mass spectrometric data. AB - A computer algorithm is described that utilizes both Edman and mass spectrometric data for simultaneous determination of the amino acid sequences of several peptides in a mixture. Gas phase sequencing of a peptide mixture results in a list of observed amino acids for each cycle of Edman degradation, which by itself may not be informative and typically requires reanalysis following additional chromatographic steps. Tandem mass spectrometry, on the other hand, has a proven ability to analyze sequences of peptides present in mixtures. However, mass spectrometric data may lack a complete set of sequence-defining fragment ions, so that more than one possible sequence may account for the observed fragment ions. A combination of the two types of data reduces the ambiguity inherent in each. The algorithm first utilizes the Edman data to determine all hypothetical sequences with a calculated mass equal to the observed mass of one of the peptides present in the mixture. These sequences are then assigned figures of merit according to how well each of them accounts for the fragment ions in the tandem mass spectrum of that peptide. The program was tested on tryptic and chymotryptic peptides from hen lysozyme, and the results are compared with those of another computer program that uses only mass spectral data for peptide sequencing. In order to assess the utility of this method the program is tested using simulated mixtures of varying complexity and tandem mass spectra of varying quality. PMID- 1304387 TI - Catalytically competent human and bovine zeta-thrombin and chimeras generated from unfolded polypeptide chains. AB - Human and bovine alpha-thrombin cleaved at the B-chain by chymotrypsin generates catalytically competent zeta-thrombins, which are comprised of two noncovalently linked fragments: a 36-(human) or 49-(bovine) residue A-chain linked by a disulfide to B-chain residues B1-148 (zeta 1-thrombin) and B-chain residues B149 259 (zeta 2-thrombin). Human and bovine D-Phe-Pro-Arg-CH2-zeta- and PhMeSO2-zeta thrombins were prepared by reaction of the active-site histidine (H-B43) and serine (S-B205) with PPACK and PMSF, respectively. Unfolding and dissociation of the noncovalently linked polypeptide chains of either human or bovine D-Phe-Pro Arg-CH2-zeta- and PhMeSO2-zeta-thrombins in 4.5 M guanidine-HCl and refolding upon 30-fold dilution in 50 mM sodium phosphate buffer pH 6.5, 750 mM NaCl, 0.1% PEG resulted in biphasic generation of catalytic activity. The slow phase was eliminated in the presence of the competitive inhibitor benzamidine-HCl. Unfolding and refolding mixtures of the appropriate inactive precursors generated the active chimeric thrombins bovine zeta 1-thrombin:human zeta 2-thrombin and human zeta 1-thrombin:bovine zeta 2-thrombin. Human zeta 1-thrombin and zeta 2 thrombin were isolated, and, upon recombining, the isolated fragments refolded to generate catalytically competent zeta-thrombin with an active-site content, specific activity toward Chromozym-TH, and a specificity constant (kcat/Km) for FPA release from fibrinogen that were all within 60% of those of native alpha thrombin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304390 TI - Control of phosphorylase b conformation by a modified cofactor: crystallographic studies on R-state glycogen phosphorylase reconstituted with pyridoxal 5' diphosphate. AB - Previous crystallographic studies on glycogen phosphorylase have described the different conformational states of the protein (T and R) that represent the allosteric transition and have shown how the properties of the 5'-phosphate group of the cofactor pyridoxal phosphate are influenced by these conformational states. The present work reports a study on glycogen phosphorylase b (GPb) complexed with a modified cofactor, pyridoxal 5'-diphosphate (PLPP), in place of the natural cofactor. Solution studies (Withers, S.G., Madsen, N.B., & Sykes, B.D., 1982, Biochemistry 21, 6716-6722) have shown that PLPP promotes R-state properties of the enzyme indicating that the cofactor can influence the conformational state of the protein. GPb complexed with pyridoxal 5'-diphosphate (PLPP) has been crystallized in the presence of IMP and ammonium sulfate in the monoclinic R-state crystal form and the structure refined from X-ray data to 2.8 A resolution to a crystallographic R value of 0.21. The global tertiary and quaternary structure in the vicinity of the Ser 14 and the IMP sites are nearly identical to those observed for the R-state GPb-AMP complex. At the catalytic site the second phosphate of PLPP is accommodated with essentially no change in structure from the R-state structure and is involved in interactions with the side chains of two lysine residues (Lys 568 and Lys 574) and the main chain nitrogen of Arg 569. Superposition of the T-state structure shows that were the PLPP to be incorporated into the T-state structure there would be a close contact with the 280s loop (residues 282-285) that would encourage the T to R allosteric transition. The second phosphate of the PLPP occupies a site that is distinct from other dianionic binding sites that have been observed for glucose-1 phosphate and sulfate (in the R state) and for heptulose-2-phosphate (in the T state). The results indicate mobility in the dianion recognition site, and the precise position is dependent on other linkages to the dianion. In the modified cofactor the second phosphate site is constrained by the covalent link to the first phosphate of PLPP. The observed position in the crystal suggests that it is too far from the substrate site to represent a site for catalysis. PMID- 1304389 TI - Multiple phosphate positions in the catalytic site of glycogen phosphorylase: structure of the pyridoxal-5'-pyrophosphate coenzyme-substrate analog. AB - The three-dimensional structure of an R-state conformer of glycogen phosphorylase containing the coenzyme-substrate analog pyridoxal-5'-diphosphate at the catalytic site (PLPP-GPb) has been refined by X-ray crystallography to a resolution of 2.87 A. The molecule comprises four subunits of phosphorylase related by approximate 222 symmetry. Whereas the quaternary structure of R-state PLPP-GPb is similar to that of phosphorylase crystallized in the presence of ammonium sulfate (Barford, D. & Johnson, L.N., 1989, Nature 340, 609-616), the tertiary structures differ in that the two domains of the PLPP-GPb subunits are rotated apart by 5 degrees relative to the T-state conformation. Global differences among the four subunits suggest that the major domains of the phosphorylase subunit are connected by a flexible hinge. The two different positions observed for the terminal phosphate of the PLPP are interpreted as distinct phosphate subsites that may be occupied at different points along the reaction pathway. The structural basis for the unique ability of R-state dimers to form tetramers results from the orientation of subunits with respect to the dyad axis of the dimer. Residues in opposing dimers are in proper registration to form tetramers only in the R-state. PMID- 1304391 TI - Kinetic properties of tetrameric glycogen phosphorylase b in solution and in the crystalline state. AB - R-state monoclinic P2(1) crystals of phosphorylase have been shown to be catalytically active in the presence of an oligosaccharide primer and glucose-1 phosphate in 0.9 M ammonium sulfate, 10 mM beta-glycerophosphate, 0.5 mM EDTA, and 1 mM dithiothreitol, the medium in which the crystals are grown or equilibrated for crystallographic studies (Barford, D. & Johnson, L.N., 1989, Nature 360, 609-616; Barford, D., Hu, S.-H., & Johnson, L.N., 1991, J. Mol. Biol. 218, 233-260). Kinetic data suggest that the activity of crystalline tetrameric phosphorylase is similar to that determined in solution for the enzyme tetramer. However, large differences were found in the maximal velocities for both oligosaccharide or glucose-1-phosphate substrates between the soluble dimeric and crystalline tetrameric enzyme. PMID- 1304392 TI - Steric exclusion is the principal source of the preferential hydration of proteins in the presence of polyethylene glycols. AB - The preferential interactions of bovine serum albumin, lysozyme, chymotrypsinogen, ribonuclease A, and beta-lactoglobulin with polyethylene glycols (PEGs) of molecular weight 200-6,000 have been measured by dialysis equilibrium coupled with high precision densimetry. All the proteins were found to be preferentially hydrated in all the PEGs, and the magnitude of the preferential hydration increased with increasing PEG size for each protein. The change in the chemical potentials of the proteins with the addition of the PEGs had highly positive values, indicating a strong thermodynamic destabilization of the system by the PEGs. A viscosity study of the PEGs showed them to be randomly coiled polymers, as their radii of gyration were related to the molecular weight by Rg = aM0.55. The thickness of the effective shell impenetrable to PEG around protein molecules, calculated from the preferential hydration, was found to vary with PEG molecular weight in similar fashion as the PEG radius of gyration, supporting the proposal (Arakawa, T. & Timasheff, S.N., 1985a, Biochemistry 24, 6756-6762) that the preferential exclusion of PEGs from proteins is due principally to the steric exclusion of PEG from the protein domain, although favorable interactions with protein surface residues, in particular nonpolar ones, may compete with the exclusion. These thermodynamically unfavorable preferential exclusion interactions lead to the action of PEGs as precipitants, although they may destabilize protein structure at higher temperatures. PMID- 1304393 TI - Avian 3-hydroxy-3-methylglutaryl-CoA lyase: sensitivity of enzyme activity to thiol/disulfide exchange and identification of proximal reactive cysteines. AB - Catalysis by purified avian 3-hydroxy-3-methylglutaryl-CoA lyase is critically dependent on the reduction state of the enzyme, with less than 1% of optimal activity being observed with the air-oxidized enzyme. The enzyme is irreversibly inactivated by sulfhydryl-directed reagents with the rate of this inactivation being highly dependent upon the redox state of a critical cysteine. Methylation of reduced avian lyase with 1 mM 4-methylnitrobenzene sulfonate results in rapid inactivation of the enzyme with a k(inact) of 0.178 min-1. The oxidized enzyme is inactivated at a sixfold slower rate (k(inact) = 0.028 min-1). Inactivation of the enzyme with the reactive substrate analog 2-butynoyl-CoA shows a similar dependence upon the enzyme's redox state, with a sevenfold difference in k(inact) observed with oxidized vs. reduced forms of the enzyme. Chemical cross-linking of the reduced enzyme with stoichiometric amounts of the bifunctional reagents 1,3 dibromo-2-propanone (DBP) or N,N'-ortho-phenylene-dimaleimide (PDM) coincides with rapid inactivation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of enzyme treated with bifunctional reagent reveals a band of twice the molecular weight of the lyase monomer, indicating that an intersubunit cross-link has been formed. Differential labeling of native and cross-linked protein with [1-14C]iodoacetate has identified as the primary cross-linking target a cysteine within the sequence VSQAACR, which maps at the carboxy-terminus of the cDNA-deduced sequence of the avian enzyme (Mitchell, G.A., et al., 1991, Am. J. Hum. Genet. 49, 101). In contrast, bacterial HMG-CoA lyase, which contains no corresponding cysteine, is not cross-linked by comparable treatment with bifunctional reagent. These results provide evidence for a potential regulatory mechanism for the eukaryotic enzyme via thiol/disulfide exchange and identify a cysteinyl residue with the reactivity and juxtaposition required for participation in disulfide formation. PMID- 1304394 TI - Structure of a rapidly formed intermediate in ribonuclease T1 folding. AB - Kinetic intermediates in protein folding are short-lived and therefore difficult to detect and to characterize. In the folding of polypeptide chains with incorrect isomers of Xaa-Pro peptide bonds the final rate-limiting transition to the native state is slow, since it is coupled to prolyl isomerization. Incorrect prolyl isomers thus act as effective traps for folding intermediates and allow their properties to be studied more easily. We employed this strategy to investigate the mechanism of slow folding of ribonuclease T1. In our experiments we use a mutant form of this protein with a single cis peptide bond at proline 39. During refolding, protein chains with an incorrect trans proline 39 can rapidly form extensive secondary structure. The CD signal in the amide region is regained within the dead-time of stopped-flow mixing (15 ms), indicating a fast formation of the single alpha-helix of ribonuclease T1. This step is correlated with partial formation of a hydrophobic core, because the fluorescence emission maximum of tryptophan 59 is shifted from 349 nm to 325 nm within less than a second. After about 20 s of refolding an intermediate is present that shows about 40% enzymatic activity compared to the completely refolded protein. In addition, the solvent accessibility of tryptophan 59 is drastically reduced in this intermediate and comparable to that of the native state as determined by acrylamide quenching of the tryptophan fluorescence. Activity and quenching measurements have long dead-times and therefore we do not know whether enzymatic activity and solvent accessibility also change in the time range of milliseconds. At this stage of folding at least part of the beta-sheet structure is already present, since it hosts the active site of the enzyme. The trans to cis isomerization of the tyrosine 38-proline 39 peptide bond in the intermediate and consequently the formation of native protein is very slow (tau = 6,500 s at pH 5.0 and 10 degrees C). It is accompanied by an additional increase in tryptophan fluorescence, by the development of the fine structure of the tryptophan emission spectrum, and by the regain of the full enzymatic activity. This indicates that the packing of the hydrophobic core, which involves both tryptophan 59 and proline 39, is optimized in this step. Apparently, refolding polypeptide chains with an incorrect prolyl isomer can very rapidly form partially folded intermediates with native-like properties. PMID- 1304395 TI - Molecular dynamics studies of a DNA-binding protein: 1. A comparison of the trp repressor and trp aporepressor aqueous simulations. AB - The results of two 30-ps molecular dynamics simulations of the trp repressor and trp aporepressor proteins are presented in this paper. The simulations were obtained using the AMBER molecular mechanical force field and in both simulations a 6-A shell of TIP3P waters surrounded the proteins. The trp repressor protein is a DNA-binding regulatory protein and it utilizes a helix-turn-helix (D helix-turn E helix) motif to interact with DNA. The trp aporepressor, lacking two molecules of the L-tryptophan corepressor, cannot bind specifically to DNA. Our simulations show that the N- and C-termini and the residues in and near the helix-turn-helix motifs are the most mobile regions of the proteins, in agreement with the X-ray crystallographic studies. Our simulations also find increased mobility of the residues in the turn-D helix-turn regions of the proteins. We find the average distance separating the DNA-binding motifs to be larger in the repressor as compared to the aporepressor. In addition to examining the protein residue fluctuations and deviations with respect to X-ray structures, we have also focused on backbone dihedral angles and corepressor hydrogen-bonding patterns in this paper. PMID- 1304396 TI - Molecular dynamics studies of a DNA-binding protein: 2. An evaluation of implicit and explicit solvent models for the molecular dynamics simulation of the Escherichia coli trp repressor. AB - Although aqueous simulations with periodic boundary conditions more accurately describe protein dynamics than in vacuo simulations, these are computationally intensive for most proteins. Trp repressor dynamic simulations with a small water shell surrounding the starting model yield protein trajectories that are markedly improved over gas phase, yet computationally efficient. Explicit water in molecular dynamics simulations maintains surface exposure of protein hydrophilic atoms and burial of hydrophobic atoms by opposing the otherwise asymmetric protein-protein forces. This properly orients protein surface side chains, reduces protein fluctuations, and lowers the overall root mean square deviation from the crystal structure. For simulations with crystallographic waters only, a linear or sigmoidal distance-dependent dielectric yields a much better trajectory than does a constant dielectric model. As more water is added to the starting model, the differences between using distance-dependent and constant dielectric models becomes smaller, although the linear distance-dependent dielectric yields an average structure closer to the crystal structure than does a constant dielectric model. Multiplicative constants greater than one, for the linear distance-dependent dielectric simulations, produced trajectories that are progressively worse in describing trp repressor dynamics. Simulations of bovine pancreatic trypsin were used to ensure that the trp repressor results were not protein dependent and to explore the effect of the nonbonded cutoff on the distance-dependent and constant dielectric simulation models. The nonbonded cutoff markedly affected the constant but not distance-dependent dielectric bovine pancreatic trypsin inhibitor simulations. As with trp repressor, the distance-dependent dielectric model with a shell of water surrounding the protein produced a trajectory in better agreement with the crystal structure than a constant dielectric model, and the physical properties of the trajectory average structure, both with and without a nonbonded cutoff, were comparable. PMID- 1304397 TI - Expression, purification, and characterization of the functional dimeric cytoplasmic domain of human erythrocyte band 3 in Escherichia coli. AB - The cytoplasmic domain of the human erythrocyte membrane protein, band 3 (cdb3), contains binding sites for hemoglobin, several glycolytic enzymes, band 4.1, band 4.2, and ankyrin, and constitutes the major linkage between the membrane skeleton and the membrane. Although erythrocyte cdb3 has been partially purified from proteolyzed red blood cells, further separation of the water-soluble 43-kDa and 41-kDa proteolytic fragments has never been achieved. In order to obtain pure cdb3 for crystallization and site-directed mutagenesis studies, we constructed an expression plasmid that has a tandemly linked T7 promoter placed upstream of the N-terminal 379 amino acids of the erythrocyte band 3 gene. Comparison of several Escherichia coli strains led to the selection of the BL21 (DE3) strain containing the pLysS plasmid as the best host for efficient production of cdb3. About 10 mg of recombinant cdb3 can be easily purified from 4 L of E. coli culture in two simple steps. Comparison of cdb3 released from the red blood cell by proteolysis with recombinant cdb3 reveals that both have the same N-terminal sequence, secondary structure, and pH-dependent conformational change. The purified recombinant cdb3 is also a soluble stable dimer with the same Stokes radius as erythrocyte cdb3. The affinities of the two forms of cdb3 for ankyrin are essentially identical; however, recombinant cdb3 with its unblocked N-terminus exhibits a slightly lower affinity for aldolase. PMID- 1304398 TI - Accelerated high-sensitivity microsequencing of proteins and peptides using a miniature reaction cartridge. AB - Greatly reduced automated protein sequencing degradation times of less than 25 min with concurrent on-line phenylthiohydantoin (PTH) derivative analysis times of less than 16 min have been achieved by using a miniaturized reaction cartridge with optimized chemical and analytical cycles. Using this method a wide range of standard and novel peptides and proteins have been sequenced with reproducibly high initial and repetitive cycle yields. In these accelerated analyses the recovery of the more labile PTH derivatives was markedly improved by using elevated pressure during cleavage steps and temperature programming throughout the Edman cycle. PMID- 1304400 TI - 'Run out and get me a four-year-old child'. PMID- 1304399 TI - A common domain within the proenzyme regions of the Drosophila snake and easter proteins and Tachypleus proclotting enzyme defines a new subfamily of serine proteases. PMID- 1304401 TI - Complement and lupus: old concepts and new directions. AB - In this review it is our intention to outline briefly the relevance of the complement system in systemic lupus erythematosus. Three main issues will be addressed: the role of complement in handling immune complexes (ICs), the association between complement deficiencies and IC diseases, and the value of measuring complement components and their conversion products in monitoring disease activity. PMID- 1304402 TI - Treatment of cutaneous lupus erythematosus. AB - The mainstays of treatment of cutaneous lupus erythematosus (LE) are topical and intralesional steroids, sunscreen, and the antimalarials. However, the practitioner is often faced with the challenge of cutaneous disease unresponsive to these conventional measures. We present our approach to the management of cutaneous LE and review the literature regarding therapy of refractory disease. PMID- 1304404 TI - Lupus-derived human monoclonal IgM anti-DNA antibody displays monospecificity, high affinity and private idiotype specificity. AB - A human monoclonal IgM k anti-DNA antibody, designated 2F7, was prepared by somatic hybridization of peripheral blood lymphocytes from a lupus patient with a human-mouse heterohybridoma cell line, K6H6/B5. 2F7 was tested for its antigen binding and idiotypic specificity by direct binding and inhibition enzyme-linked immunosorbent assays. 2F7 had a high binding activity to single-stranded DNA (ssDNA) but not to double-stranded DNA. It cross-reacted with single-stranded homopolymers with pyrimidine bases and double-stranded polynucleotides containing those homopolymers, suggesting that 2F7 recognizes a conformational determinant made up of both deoxyribose-phosphate backbone and specific nucleotide base. 2F7 did not cross-react with eight structurally unrelated self-antigens. Dissociation constant (Kd) of 2F7 for sonicated ssDNA was approximately 4.5 x 10(-9) M, indicating its relatively high affinity. Idiotypic characterization with rabbit anti-idiotype raised against 2F7 suggested that 2F7 expressed an idiotype at or near its antigen-binding sites that was not detected in sera from 20 unrelated lupus patients, 10 lupus family members and 10 normal individuals. These results suggest that certain IgM class anti-DNA antibodies in human systemic lupus erythematosus may arise by antigen stimulation and not simply by polyclonal B cell activation. PMID- 1304403 TI - The heart and antiphospholipid antibodies in MRL-lpr/lpr mice. AB - Our objective in this study was to determine possible associations between antiphospholipid antibodies (aPL) and histologically defined heart valve lesions in the MRL-lpr/lpr mouse, a suitable model for the antiphospholipid syndrome (APS). At monthly intervals, from 2 to 6 months of age, three MRL-lpr/lpr mice (two with anticardiolipin antibodies, one without) and two sex- and age-matched Balb/c mice (controls) were sacrificed for histological studies. Serum binding to phospholipids and DNA was studied at this time. We found thickened heart valves in 68% of MRL-lpr/lpr mice and in 80% of Balb/c mice, and no association with any of the antibodies tested was found. No evidence of coronary vasculitis or thrombi was found in any of the mice studied. Platelet counts in MRL-lpr/lpr mice were significantly lower (640.550 +/- 211.818 x 10(6)/ml) than in Balb/c mice (780.0 + 112.5 x 10(6)/ml) (p < 0.05), and no association was found between platelet counts and aPL. In this model of murine APS, aPL bear no importance in heart valve pathology. PMID- 1304405 TI - The clinical significance of measuring different anti-dsDNA antibodies by using the Farr assay, an enzyme immunoassay and a Crithidia luciliae immunofluorescence test. AB - Anti-double-stranded DNA (dsDNA) antibodies are highly specific for the diagnosis of systemic lupus erythematosus (SLE) but are heterogeneous in respect to, for example, avidity, class and cross-reactivity. Sera from 2061 patients were measured by three methods: an enzyme-linked immunosorbent assay (ELISA), an indirect immunofluorescence test with Crithidia luciliae as substrate (CLIF), and the Farr assay, a radioimmunological method based on the ammonium sulfate precipitation of immune complexes. The different anti-dsDNA antibody determinations were evaluated by analysis of patient records. The reason for a reactive Farr assay in 14 patients was predominantly the measurement of antibodies of the IgM class, which are not detected by the ELISA. The detection of additional antibodies to dsDNA of the IgA class, to single-stranded DNA or to histones plays a minor role. In comparison with the Farr assay, we found more positive results with the ELISA, which additionally detects anti-dsDNA antibodies of low avidity. The ELISA might also yield positive values in conditions such as chronic liver diseases, various infections and connective tissue diseases other than SLE. Avoiding the disadvantages of radioactivity, the ELISA is well suited as a screening test for dsDNA antibodies. However, positive results should be confirmed by the CLIF test or preferably by the Farr assay, thus combining sensitivity with specificity. PMID- 1304406 TI - Pneumocystis carinii pneumonia in patients with systemic lupus erythematosus. AB - At the University Hospital, Kuala Lumpur, Malaysia, nine patients with systemic lupus erythematosus (SLE) were treated for Pneumocystis carinii pneumonia (PCP) between January 1987 and December 1988. When they developed PCP all the patients' SLE disease course was active and eight of them were on prednisolone. Four of these eight patients were also receiving cyclophosphamide. Patients who were on more intensive immunosuppressive therapy were found to develop more severe PCP. All the patients except one were treated with high-dose cotrimoxazole. Four patients responded to antipneumocystis treatment and survived, while PCP was responsible for the death of the five non-survivors. PMID- 1304407 TI - Lack of specific binding of anticardiolipin antibodies to intact platelets. AB - The aims of this study were to investigate whether anticardiolipin antibodies (aCL) bind to intact (resting or activated) platelets in vitro. Suspensions of resting, activated (with a mixture of thrombin and collagen) and freeze-thawed platelets from healthy subjects were incubated with either affinity-purified aCL or pooled normal human immunoglobulin G (IgG). Platelet-bound IgG was measured by flow cytometric analysis of platelets incubated with a fluorescein-conjugated polyclonal goat anti-human IgG. There was no significant binding of IgG aCL to intact resting or activated platelets, while significant specific binding to freeze-thawed platelets was demonstrated. These results question the theory that aCL bind/activate intact platelets in vivo. PMID- 1304408 TI - IgG subclasses in systemic lupus erythematosus and other autoimmune rheumatic diseases. AB - In this study the concentration of the different subclasses of IgG in sera from patients with a range of autoimmune rheumatic diseases (ARD) was detected by radial immunodiffusion. In the second part the IgG subclasses of autoantibodies that recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), Ro, La, Sm and RNP in patients with ARD were measured by enzyme-linked immunosorbent assay. We studied 15 patients with lupus, 20 patients each with primary and secondary Sjogren's syndrome (SS) and 10 each with rheumatoid arthritis (RA), scleroderma and myositis. Twenty healthy controls were also measured. The serum concentration of IgG2 in ARD patients was generally reduced. In contrast, the concentrations of IgG1, IgG3 and IgG4 subclasses were normal or raised. A high degree of correspondence in the IgG1, IgG2 and IgG3 responses to dsDNA and ssDNA in SLE was found. Notable differences in the IgG1 anti-Ro and ssDNA responses compared to the other subclasses were seen in 1 degree and 2 degrees SS. In addition, an unexpected high level of IgG4 antibodies to ssDNA in 1 degree SS (65%) and IgG4 antibodies to Sm/RNP in RA was observed. PMID- 1304409 TI - High-dose intravenous methylprednisolone therapy associated with osteonecrosis in patients with systemic lupus erythematosus. AB - Osteonecrosis is related to the use of steroids in patients with systemic lupus erythematosus (SLE); its association with the use of 'pulses' of methylprednisolone (PMP) is not clear at present. In a retrospective analysis of 190 patients with SLE we found that 19% of 36 patients treated with PMP had osteonecrosis compared with 6% of 154 patients without that treatment (P < 0.04). Risk factors associated with osteonecrosis were PMP treatment, cushingoid appearance, steroid doses > or = 40 mg/day during the first month of treatment, a ratio of steroid dose in grams/year > or = 12, hematuria and proteinuria. In a stepwise regression model, when cushingoid appearance was excluded, PMP became the only significant factor (P = 0.045). We conclude that osteonecrosis can be considered a long-term complication of PMP treatment in SLE patients. PMID- 1304410 TI - Right recurrent laryngeal nerve palsy in a patient with systemic lupus erythematosus. PMID- 1304411 TI - Antiphospholipid antibodies and shrinking lungs in SLE. PMID- 1304412 TI - Conduction disturbance and pacemaker therapy in patients with corrected transposition of the great arteries. AB - We observed 4 adult patients with corrected transposition of the great arteries (CTGA) who developed complete atrioventricular block: of 4 patients, 2 received endocardial pacemakers (DDD mode), 1 an epicardial pacemaker (VVI mode), and 1 patient did not have a permanent pacemaker implantation. Endocardial lead fixation in the systemic venous atrium and ventricle is adequate to provide permanent electrode stability in patients with CTGA. PMID- 1304413 TI - Percutaneous transradial approach for coronary angiography. AB - A percutaneous radial artery approach for coronary angiography was performed in 40 patients using a 5-F catheter. The patients, in whom the femoral artery approach was difficult or contraindicated because of advanced arteriosclerosis, were selected on the basis of easily palpable radial and ulnar arteries and a normal Allen test. In 1 patient the catheter could not be advanced to the brachial artery, and subsequently this patient underwent the brachial approach. In all 39 patients, selective left coronary angiography was accomplished using a left Judkins catheter, and the right coronary artery and the saphenous vein graft were entered successfully using a right Judkins or Amplatz catheter. All patients had excellent quality of images of coronaries and vein grafts. In 5 patients (13%), the pulse remained acutely diminished, but there were no evidences or complaints of pain. Bleeding at the puncture site occurred in 1 patient (3%), and 5 patients (13%) had subcutaneous bleeding around the puncture site. Pseudoaneurysm, nerve injury and arteriovenous fistula were not detected at the time of discharge. PMID- 1304414 TI - Combined effect of captopril and aspirin in renal hemodynamics in elderly patients with congestive heart failure. AB - Captopril and aspirin have been claimed to adversely affect renal function. This study was designed to evaluate the safety of concomitant administration of both drugs in patients with moderate to severe congestive heart failure (CHF). The study group consisted of 10 patients with a mean age of 77.6 +/- 4.4 years and a mean New York Heart Association functional class of 2.6 +/- 0.5. Captopril was administered in a rapidly escalating dose regimen over a 4-day period to a maximum dose of 75 mg/day. Aspirin 0.25 g/day was added from day 5 on. Renal plasma flow (RPF) was measured by iodohippurate scan and the creatinine clearance test (Ccr) was used as an index of glomerular filtration rate (GFR). Both Ccr and RPF remained unchanged throughout the study period; 48.9 +/- 16; 48.2 +/- 16.5; 49.4 +/- 16, and 222 +/- 67, 241 +/- 97, 237 +/- 88 ml/min, for days 0, 4, 9, respectively. Only 1 patient developed a significant decrease in Ccr following the administration of captopril. This patient had a further decrease when aspirin was added. The decrease in Ccr was accompanied by a marked reduction in filtration fraction and in mean arterial pressure. Our data suggest that the administration of aspirin to elderly patients with moderate CHF treated with captopril is relatively safe and is not associated with further deterioration in renal function. PMID- 1304415 TI - Transient cardiac pacing is insufficiently used to treat arrhythmia associated with thioridazine. AB - All cases of arrhythmias associated with thioridazine were reviewed (177 cases). No case of severe ventricular arrhythmia was reported in children. In adults, at therapeutic doses, ventricular tachycardia or fibrillation (VT/VF) or torsade de pointes was observed mainly in patients with concomitant risk factors. At doses higher than 800 mg, atrioventricular (A-V) and bundle branch blocks were associated with VT/VF. Mortality was higher in patients with A-V blocks. Although transient cardiac pacing is known to be efficacious to control phenothiazine induced arrhythmias, it was rarely used. PMID- 1304416 TI - Prognostic value of thallium-201 exercise scintigraphy in low-risk patients after Q-wave myocardial infarction: comparison with exercise testing and catheterization. AB - In a prospective study of 100 consecutive patients discharged after a Q-wave myocardial infarction, the value of reversible ischemia on thallium-201 scintigraphy to assess the risk of cardiac events (death or reinfarction) during 4 years was compared with variables from exercise testing and cardiac catheterization. Patients with markedly impaired left ventricular function [ejection fraction (EF) < or = 0.30] were excluded. During follow-up there were 20 cardiac events (10 cardiac deaths and 10 reinfarctions). Thallium-201 scintigraphy was significantly better than all exercise test variables and better than an EF < 0.40, with good sensitivity and specificity (75 and 51%, respectively). Exercise-induced reversible ischemia on scintigraphy yielded the same information as the presence of multivessel disease. Exercise test variables were of limited value to assess prognosis. Thus, thallium-201 scintigraphy can be used as the only tool to predict future cardiac events in low-risk patients after a Q-wave myocardial infarction. PMID- 1304417 TI - Correlation of coronary artery stenosis site with anterior or inferior projection of ST changes induced by treadmill exercise using a newly devised 9-lead Holter method. AB - A 9-lead Holter monitor using the lead-switching technique (9-lead DCG) and conventional 12-lead electrocardiograph (12-lead ECG) were simultaneously used for recording during treadmill exercise testing (Td-test) in 140 patients with coronary artery disease. Coronary arteriography was performed in 118 of the 140 patients, and the correlation between coronary stenosis and anterior or inferior projection of ST depressions occurring during the Td-test was investigated. Additionally, 10 patients with acute myocardial infarction (AMI) were studied to test ST elevation detection by the 9-lead DCG. The CM5 lead demonstrated ST depressions in 92 of the 109 patients showing ST depressions in one or more leads. High lateral (HL) and/or low lateral leads detected all ST depressions occurring in the I and aVL leads of the 12-lead ECG. Leads CM1, CM2 and CM3 exhibited low sensitivity (0-32%) and high specificity (56-100%), while leads CM4, CM5, and CM6 provided greater sensitivity (66-95%), but less specificity (3 32%) in detecting diseases of the left anterior descending artery, left circumflex artery and/or right coronary artery (RCA). In contrast, the low back (LB) lead demonstrated high sensitivity (88%) and high specificity (86%) in detecting RCA disease. Lead CM3 detected ST elevations in all 6 patients with anterior AMI, while the LB lead did so in all 4 patients with inferior AMI. With a Holter monitor, 4 leads are needed: CM5 like, CM3 like, lateral (such as HL) and inferior (such as LB). The LB lead is useful in detecting inferior ischemia. PMID- 1304418 TI - Prevalence of physiological valvular regurgitation in hypertensive patients: echocardiographic and color Doppler study. AB - Since the advent of the Doppler color flow echocardiography, the presence of a small degree of insufficiency of the cardiac valves has been detected with relative frequency in structurally and functionally normal hearts. Data about this so-called 'physiological' regurgitation are presently available only in normotensive subjects and athletes. We therefore studied the prevalence of this phenomenon in a group of patients with essential hypertension compared to a population of normotensive subjects. To this purpose, a Doppler color flow echocardiographic study was performed in 130 essential hypertensive patients (72M/58F; age 44.2 +/- 13.5 years; BP 154.3 +/- 12.8/98.3 +/- 7.1 mm Hg) without any evidence of left ventricular hypertrophy or cardiopathy and in 100 normal subjects (59M/41F; age 41.2 +/- 14.8 years; BP 119.1 +/- 8.1/79.2 +/- 8.1 mm Hg). We conclude that in patients with essential hypertension the physiological regurgitant jets are present in one or more cardiac valves; moreover, the regurgitation of the mitral and aortic valve is found with more frequency than in the normotensive control group (36.1 vs. 27.0% and 17.7 vs. 11.0%, respectively). These data suggest that the increased afterload of the left ventricle may play an important role in the pathogenesis of even minor degree of insufficiency of the cardiac valves. As this finding does not appear to have a pathological relevance, the main clinical implication of this study is that it is not advisable to create a jatrogenic heart disease in the hypertensive patients routinely screened by the echo-Doppler technique. PMID- 1304419 TI - How lymph is drained away from the human papillary muscle: anatomical conditions. AB - The lymphatic and venous bed was evaluated in 42 human heart papillary muscles. The lymphatics form networks in the superficial and deep layers of the subendocardium and in the myocardium of the papillary muscles. In the apical area, the subendocardial lymphatics gradually merge with the fine myocardial, developing arcades at the origins of chordae tendineae. Thicker myocardial lymphatics leave the area passing along the connective tissue septa, often in close vicinity to the blood vessels. The injection method failed to reveal deep lymphatics in the connective tissue of chordae tendineae. Lymphovenous anastomoses were disclosed in the papillary muscle. The possible morphological pathways for lymphatic drainage of the papillary muscle are as follows: (1) the lymphatic bed subendocardial and myocardial, joining on the ventricular wall bed at the muscle base, and (2) lymphovenous anastomoses, passing along from the myocardial and subendocardial lymphatic bed into the ventricular wall veins and the sinus coronarius system, or into the thebesian veins and further directly into the heart ventricles. PMID- 1304421 TI - Meiosis: components and process in nuclear differentiation. PMID- 1304420 TI - Extensive hemorrhagic myocardial infarction associated with left atrial myxoma. PMID- 1304422 TI - Characterization of REC104, a gene required for early meiotic recombination in the yeast Saccharomyces cerevisiae. AB - The REC104 gene was initially defined by mutations that rescued the inviability of a rad52 spo 13 haploid strain in meiosis. We have observed that rec104 mutant strains undergo essentially no induction of meiotic gene conversion, and we have not been able to detect any meiotic crossing over in such strains. The REC104 gene has no apparent role in mitosis, since mutations have no observable effect on growth, mitotic recombination, or DNA repair. The DNA sequence of REC104 reveals that it is a previously unknown gene with a coding region of 549-bp, and genetic mapping has localized the gene to chromosome VIII near FUR1. Expression of the REC104 gene is induced in meiosis, and it appears that the gene is not transcribed in mitotic cells. Possible roles for the REC104 gene product in meiosis are discussed. PMID- 1304423 TI - Searching for synaptonemal complex proteins and their genes. AB - As an alternative to the production and use of monoclonal antisynaptonemal complex (SC) antibodies to isolate SC genes, we have explored the use of polyclonal anti-SC antibodies to identify SC genes from a cDNA expression library. The method proved relatively simple, reliable, and fast and has yielded two SC genes. A homologue of one of these genes from a different species has previously been isolated in another laboratory. PMID- 1304424 TI - There are two mechanisms of achiasmate segregation in Drosophila females, one of which requires heterochromatic homology. AB - There are numerous examples of the regular segregation of achiasmate chromosomes at meiosis I in Drosophila melanogaster females. Classically, the choice of achiasmate segregational partners has been thought to be independent of homology, but rather made on the basis of availability or similarities in size and shape. To the contrary, we show here that heterochromatic homology plays a primary role in ensuring the proper segregation of achiasmate homologs. We observe that the heterochromatin of chromosome 4 functions as, or contains, a meiotic pairing site. We show that free duplications carrying the 4th chromosome pericentric heterochromatin induce high frequencies of 4th chromosome nondisjunction regardless of their size. Moreover, a duplication from which some of the 4th chromosome heterochromatin has been removed is unable to induce 4th chromosome nondisjunction. Similarly, in the absence of either euchromatic homology or a size similarity, duplications bearing the X chromosome heterochromatin also disrupt the segregation of two achiasmate X chromosome centromeres. Although heterochromatic regions are sufficient to conjoin nonexchange homologues, we confirm that the segregation of heterologous chromosomes is determined by size, shape, and availability. The meiotic mutation Axs differentiates between these two processes of achiasmate centromere coorientation by disrupting only the homology-dependent mechanism. Thus there are two different mechanisms by which achiasmate segregational partners are chosen. We propose that the absence of diplotene-diakinesis during female meiosis allows heterochromatic pairings to persist until prometaphase and thus to co-orient homologous centromeres. We also propose that heterologous disjunctions result from a separate and homology independent process that likely occurs during prometaphase. The latter process, which may not require the physical association of segregational partners, is similar to those observed in many insects, in Saccharomyces cerevisiae and in C. elegans males. We also suggest that the physical basis of this process may reflect known properties of the Drosophila meiotic spindle. PMID- 1304426 TI - Pulsed-field gel analysis of the pattern of DNA double-strand breaks in the Saccharomyces genome during meiosis. AB - Pulsed-field gel electrophoresis (PFGE) has been used to study the timing, frequency, and distribution of double-strand breaks (DSBs) in chromosomal-sized DNA during meiosis in yeast. It has previously been shown that DSBs are associated with some genetic hotspots during recombination, and it is important to know whether meiotic recombination events routinely initiate via DSBs. Two strains have been studied here--a high-sporulating homothallic wild type and a congenic mutant strain carrying a rad50S mutation. This mutant has previously been reported to accumulate broken molecules in meiosis to much higher frequencies than wild type and to abolish the characteristic wild-type processing of DNA that has been observed at the break sites. When whole chromosomes are resolved by PFGE, both strains show some broken molecules starting at the time that cells commit to genetic recombination. Breakage has been assessed primarily on Chromosome III and Chr. XV, using Southern hybridization to identify these chromosomes and their fragments. At any one time, break frequency in wild type is much lower than the cumulative frequency of recombination events that occur during meiosis. However, there is suggestive evidence that each break is short lived, and it is therefore difficult to estimate the total number of breaks that may occur. In rad50S, chromosome breaks accumulate to much higher levels, which are probably broadly consistent with the estimated number of recombination events in wild type. However, since rad50S is substantially defective in completing recombination, it is not known for certain if it initiates events at wild-type frequencies. A surprising feature of the data is that a strong banding pattern is observed in the fragment distribution from broken chromosomes in both strains, implying that at least much of the breakage occurs at specific sites or within short regions. However, with the exception of the rDNA region on Chr. XII, assessment of the genetic map indicates that recombination can occur almost anywhere in the genome, although some regions are much hotter than others. Possible reasons for this apparent paradox are discussed. It may in part result from breakage levels too low for adequate detection in cold regions but may also imply that recombination events are localized more than previously realized. Alternatively, there may be a more indirect relationship between break sites and the associated recombination events. PMID- 1304425 TI - Promoter-containing ribosomal DNA fragments function as X-Y meiotic pairing sites in D. melanogaster males. AB - The Drosophila melanogaster ribosomal DNA (rDNA) functions as an X-Y meiotic pairing site. Deletions encompassing the X chromosomal rDNA block (located in the heterochromatin) disrupt X-Y pairing and disjunction. Insertions of single, complete rRNA genes at ectopic locations on the heterochromatically deficient X partially restore X-Y pairing capacity. This study was undertaken to test fragments of an rDNA repeat for the ability to stimulate X-Y pairing and disjunction and to test for relationships between pairing capacity and two other phenotypes associated with rDNA insertions: transcription and the ability to organize a nucleolus. Insertions of three different fragments, all of which retained the rDNA promoter and upstream spacer sequences and which differed among each other in the length of downstream sequences, were obtained by P-element mediated transformation. One of the fragments is truncated only 140bp downstream from the promoter. Insertions of all three fragments proved capable of stimulating X-Y disjunction. Double insertions were substantially more effective than single insertions. RNA/PCR analysis was used to show that transcripts initiated at the inserted rDNA promoters are present in testis RNA from all insertions. Treatment with an antinucleolar antibody revealed that none of the insertions was associated with a mininucleolus. Thus promoter-containing rDNA fragments are autonomously capable of being transcribed and of functioning as X-Y pairing sites, but not of forming a mini-nucleolus. PMID- 1304428 TI - [33rd Annual Meeting of the Japanese Society of Neurology. Kagoshima City, May 20 22, 1992. Abstracts]. PMID- 1304427 TI - Minimal extent of homology required for completion of meiotic recombination in Saccharomyces cerevisiae. AB - The minimal length of contiguous homology required for successful completion of meiotic recombination was investigated by using heterologous insertions to delimit homologous segments of chromosome III in the yeast Saccharomyces cerevisiae. Constructs created in vitro by insertion of selectable markers into the LEU2 locus were transplaced into haploid strains, which were then mated to create diploids containing pairs of insertion heterologies at various distances. Analysis of the meiotic products from these diploids revealed a gradient in the frequency of both reciprocal and nonreciprocal recombination declining monotonically from the 5' end of LEU2. Both types of event were found to be restricted by the presence of the insertion heterologies. The spo13 single division meiosis was exploited to develop a plating assay in which LEU2 diploid spores containing reciprocally recombinant strands derived from events occurring completely within the interval flanked by the insertion heterologies were selected by random spore methods. Reciprocal recombination frequencies measured with this assay decreased linearly with extent, extrapolating to a minimal homology requirement of 150-250 nucleotides. When homology was most severely restricted, unexpected flanking marker configurations among reciprocal recombinants within LEU2 demonstrated the occurrence of complex recombination events. In addition to detecting reciprocal recombinants, the system is capable of measuring the probability that a non-reciprocal recombination event will have one end-point between the heterologous inserts and the other lying outside the interval. The minimal length of homology required for this aspect of recombination was found to be 25-60 nucleotides. PMID- 1304429 TI - Preconditioning of heart by repeated stunning: adaptive modification of myocardial lipid membrane. AB - Recent studies indicate that preconditioning of a heart by repeated stunning protects it from subsequent ischemic injury. Such myocardial preservation is likely to be due to adaptive modification of lipid composition and dynamic structure of cellular membrane. To test this hypothesis, swine heart was subjected to four episodes of 5 min stunning by LAD occlusion, followed by 10 min of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min by LAD occlusion, followed by 6 h reperfusion. Control heart was perfused for 60 min, followed by 60 min ischemia and 6 h reperfusion. Free fatty acids (FFA) accumulated in control heart during ischemia as expected, which was further enhanced by reperfusion. The FFA level was also enhanced during ischemia in stunned myocardium. However, this FFA level was almost restored during reperfusion. The levels of polyunsaturated fatty acids (PUFA) such as oleate, linoleate, and arachidonate followed a similar pattern. Membrane fluidity, monitored by fluorescence polarization, was decreased during ischemia and reperfusion in the unstunned heart, with the corresponding increase in microviscosity. The increased microviscosity was significantly reduced by stunning. Since FFA are presumably generated from membrane phospholipids, these results suggest that stunning may cause the incorporation of a greater proportion of PUFA in membrane phospholipids, leading to preservation of membrane phospholipids and maintaining the membrane fluidity, which may be at least partially responsible for the attenuation of ischemic reperfusion injury. PMID- 1304430 TI - Microalbuminuria: frequency and clinical significance in hospital patients. AB - We investigated the frequency and the clinical significance of microalbuminuria (UA) in 312 hospital patients suspected of renal disorders, but with normal or borderline levels of urinary total protein (UTP). Approximately one-third of the patients with urinary total protein < 300 mg/g creatinine had microalbuminuria, above the reference interval (< 32 mg/g creatinine). In contrast, only 10% of the patients with elevated total urinary protein above the reference interval (> 200 mg/g creatinine) did not have microalbuminuria. About half of the patients with elevated UA had diabetes mellitus, hypertension, an immune-related disorder, or had undergone a recent renal transplant. About half of the patients with borderline elevated UTP (100 to 300 mg/g creatinine) did not have any obvious renal problem. These data demonstrate that: 1) microalbuminuria occurs very commonly in hospital patients, 2) it is a more sensitive and specific assay for the early detection of many renal disorders compared to urinary total protein, especially when the latter test is normal or borderline elevated; and 3) a thorough patient history is required for interpretation of microalbuminuria in diabetes to eliminate other complicating factors. PMID- 1304431 TI - The in vivo systemic effect of human recombinant interleukin-1 beta on fibronectin in rats. AB - The in vivo systemic effect of interleukin (IL)-1 beta on plasma and cartilage fibronectin was studied in arthritic rats, as well as alpha 1-acid glycoprotein and albumin. Plasma fibronectin showed a 27% increase in the arthritic group, while alpha 1-acid glycoprotein increased 22-fold and albumin decreased by 46%. IL-1 effect depended on the administered dose. 2 micrograms injection significantly increased plasma fibronectin and alpha 1-acid glycoprotein. In cartilage, fibronectin was significantly modified in arthritic animals but increased in a dose-related manner after IL-1 treatment. As IL-1 increases fibronectin-degrading enzyme production and as some of these fragments can develop properties that do not possess the intact molecule, one can postulate a vicious circle in matrix degradation in the inflammatory process of the joint. PMID- 1304432 TI - In vitro influence of oxygenation on enzymes of rat adipose tissue. AB - Pre-incubation of rat adipose tissue from ad lib fed rats in the presence of 1.2 U/ml insulin and 2.8 x 10(-7) M prostaglandin F2 alpha for 16 hours in a gas atmosphere of 5% O2 led to an increase in glucose-6-phosphate dehydrogenase activity. No increase in glycerol-3-phosphate dehydrogenase or hexokinase activities were noted. Actinomycin D (50 micrograms/ml) and dehydroepiandrosterone (120 micrograms/ml) attenuated this increase and the increase in incorporation of [1-14C] glucose into carbon dioxide and tissue seen under these conditions. No increase in glucose-6-phosphate dehydrogenase was seen when pre-incubation was made in a gas atmosphere containing 20% O2. Although dehydroepiandrosterone inhibited both enzyme activity and isotope incorporation in a 20% O2 gas atmosphere, actinomycin D was without effect. PMID- 1304433 TI - In vitro influence of oxygenation on lipogenesis of rat adipose tissue. AB - Pre-incubation of rat adipose tissue from ad lib fed rats in gas mixtures containing a range of oxygen concentrations from 0% oxygen to 20% oxygen showed that incorporation of isotopes of glucose into carbon dioxide and tissue were increased after pre-incubation for a period of 14-16 hours in a gas atmosphere containing 5% oxygen. This increase required the presence of 1.2 U/ml insulin in the pre-incubation medium and it was augmented by the presence of 2.8 x 10(-7) M prostaglandin F2 alpha. Incorporation into tissue was shown to be mainly into glyceride-glycerol. Similar results were obtained with isolated fat cells. PMID- 1304434 TI - Activation of PGE2-secretion from gastric mucosa by a type I phospholipase C is mediated by a direct release of arachidonic acid. AB - We investigated the effects of an exogenous Type I phospholipase C (PLC) from clostridium perfringens on arachidonic acid release and prostaglandin synthesis from gastric mucosa by determining PGE2 release from organ cultured rabbit mucosal biopsies as well as PGE2 synthesis and substrate-dependent inactivation of the prostaglandin cyclooxygenase from endogenously released arachidonic acid in mucosal homogenate. PLC dose dependently stimulated PGE2 secretion from organ cultured mucosa to 145% and 245% at 0.1 and 1.0 U/ml during a 60 minute culture period. This effect was not affected by the calmodulin antagonist N-(6 aminohexyl)-1-5-chloro-1-naphthalene-sulfonamide (W-7) or the intracellular calcium chelator 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid acetoxymethyl ester (BAPTA-AM). PLC could not be substituted by phorbol-12 myristate 13-acetate (PMA), an analogue of the diacylglycerol second messenger functions. During a 15 minute preincubation of mucosal homogenate at 37 degrees C, 1mM CaCl2 stimulated PGE2 synthesis from endogenous arachidonic acid about 5 fold compared to an EDTA-control. In contrast, the residual prostaglandin synthesizing capacity, determined by incubation with excess 14C-labelled arachidonic acid, was reduced by CaCl2 to 37% of the EDTA-value. Quinacrine, an inhibitor of arachidonic acid release from phosphatidylethanolamine, reduced both the stimulation of PGE2 synthesis and the inactivation of prostaglandin cyclooxygenase. Therefore we conclude, that this Ca(2+)-effect reflects activation of the Ca-dependent phospholipase A2 (PLA2) and, as a consequence, substrate-induced inactivation of the prostaglandin cyclooxygenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304435 TI - Ethical considerations in the social context of Huntington disease. PMID- 1304436 TI - Seminar on ethical issues arising from molecular studies in human genetic disease: held under the auspices of the UK Cancer Family Study Group in Manchester--21st May 1992. PMID- 1304437 TI - Ethical issues in genetic testing for Huntington's disease: lessons for the study of familial cancers. PMID- 1304438 TI - The use of information (autonomy and confidentiality). PMID- 1304439 TI - The patient's viewpoint. PMID- 1304440 TI - Characterization of a bovine synovial fluid lubricating factor. III. The interaction with hyaluronic acid. AB - Although hyaluronate is not a boundary lubricant in cartilaginous and latex:glass bearings, a distinct interaction with purified synovial lubricating factor (PSLF) was demonstrated by three means: 1) enhancement of lubricating ability in an artificial test system; 2) viscometry; 3) electron microscopy. The interaction was of a physical rather than a specific chemical type; it varied with the degree of purification of PSLF and of hyaluronate. The interaction accounts for retention of the relatively small PSLF molecule (approximately 280 kDa) with the synovial mucin on a 0.22 microns filter. The data provide evidence that hyaluronate and PSLF act synergistically in the boundary lubricating activity of animal joints. PMID- 1304441 TI - Inhibitors of collagenase in ligaments and tendons of rabbits immobilized for 4 weeks. AB - Our laboratories have previously measured the capacity for collagenase production by normal and immobilized rabbit periarticular connective tissues (PCT), i.e., anterior cruciate ligaments (ACL), medial collateral ligament (MCL) and patellar tendon (PT). Rabbit limbs were immobilized for 4 weeks and then the tissues were cultured for 4 days. Collagenase and inhibitor (TIMP) were measured in the medium. Collagenase activity was significantly decreased in the medium from all experimental tissues, relative to the levels in contralateral control tissues. On the other hand there was no significant change in inhibitor levels in the three experimental tissues. These results support the idea that collagenase is decreased due to decreased enzyme expression and not to increased inhibitor production. PMID- 1304442 TI - A study of some properties of mineralized turkey leg tendon. AB - Several macroscopic physical properties of mineralized turkey leg tendon were measured including wet density, composition, volume fractions of the major components, sonic velocity in three axes, longitudinal modulus and dimensional changes on drying. Where possible the properties were related to density. Typically the wet density of unmineralized tissue is 1.09 g/cc, where for fully mineralized tissue it is 1.6 g/cc (compared with 2.06 to 2.10 g/cc for compact cow bone). Longitudinal sonic velocity axially is 3.22 km/sec, 2.57 km/sec transversely and 2.21 km/sec in thickness. The axial longitudinal modulus is 16.7 GPa compared to the axial Young's modulus of 8.53 GPa. MTLT shrinks 0.5% axially, 4.75% transversely and 4.15% in thickness. The anisotropy is equally exhibited in its microscopic structure when observed optically. Least squares second order curves were fitted to the water, mineral and organic component experimental values. Apparently the water in MTLT is replaced by mineral, unlike the process in bone where there is less organic matter as the mineral content increases and the water fraction changes much less. The generalized packing model for collagen was used to relate the data to the ultrastructure. The distribution of the major components between the intrafibrillar and extrafibrillar volumes as a function of the density was calculated. The results show the intrafibrillar volume fraction increases with density, the water content of the intrafibrillar volume remains almost constant, but the water fraction of the extrafibrillar volume decreases from 51 to 8% of the water in the tissue. It is concluded that the mineralization process in MTLT differs from that in bone. PMID- 1304443 TI - Isolation and characterization of an abundant elastase inhibitor from NaCl extracts of bovine nasal septa and articular cartilage. AB - Extracts of cartilage have been reported to inhibit many serine proteinases and metalloenzymes. Such inhibition may be important in protecting cartilage against degradation by chondrocytic proteinases such as collagenase, stromelysin and by leukocytic proteases, such as elastase. We report here isolation and partial characterization of a 17-kD elastase inhibitor from 0.5 M NaCl extracts of both nasal septum cartilage and articular cartilage, which inhibits elastase and represents 0.08% of the weight of nasal cartilage and 0.002% of the weight of articular cartilage. The protein was highly specific for elastase and did not inhibit cartilage metalloproteinases, suggesting that it may be mainly directed toward protecting cartilage against leukocytic proteases. The inhibitor had a blocked amino-terminus, was high in serine and glycine and lacked carbohydrate. The ease with which the inhibitor was extracted from cartilage suggests that it may function in vivo as a highly abundant elastase inhibitor which is secreted into synovial fluid from cartilage. The inhibitor was shown to be synthesized by bovine articular cartilage in explant culture and nearly all of the metabolically labeled material was secreted into the culture media. The inhibitor cross-reacted with polyclonal antibodies to bovine neck ligament alpha-elastin and antibodies to the inhibitor reacted with bovine neck ligament elastin. The properties of this inhibitor are different than those of any other reported cartilage derived inhibitor. PMID- 1304444 TI - Collagenase-inhibitory activity in deposit and resorption phases of guinea pig carrageenin granuloma. AB - The levels of collagenase inhibitor, both free and bound to metalloproteinases, were evaluated at 7 days [deposit phase (DP)] and 14 days [resorptive phase (RP)] of evolution of the subcutaneous carrageenin-induced granuloma in the guinea pig. The level of free collagenase inhibitor was considerably higher in the supernatant of DP granulomas (7.95 +/- 1.53 U/mg protein) as compared to that of RP granulomas (2.53 +/- 0.41 U/mg protein). When the samples were heated at acid pH to release the inhibitor from metalloproteinase-inhibitor complexes, free inhibitor was recovered in both phases. However, the units of recovered collagenase inhibitor were several fold higher in all RP granulomas in comparison with DP granulomas (6.88 +/- 2.46 vs 1.5 +/- 0.53). Therefore, DP and RP tissues exhibited similar total amount of tissue inhibitor. By HPLC, collagenase inhibitor activity was localized in a fraction consistent with the size of TIMP. These results suggest a different balance of collagenase and collagenase inhibitor during the evolution of the granuloma; an excess of inhibitor over metalloproteinases appears to predominate during the phase of collagen accumulation contrasting with an inverse situation when the granuloma is healing. PMID- 1304445 TI - Influences of long-term cigarette smoke exposure on pharmacokinetics of theophylline, and on liver microsomal enzymes in rats. AB - The influences of long-term cigarette smoke exposure on pharmacokinetics of oral theophylline (20 mg/kg), and on liver microsomal enzymes which metabolize drugs were studied in rats. Animals were exposed to cigarette smoke for 20 min each in the morning and evening every day for 26 days in the pharmacokinetic study, and 27 days for the enzyme assays. Theophylline was administered 13 h after the last exposure to smoke, and plasma concentrations were measured using HPLC. Plasma concentrations of theophylline during the absorption phase and 6 h after oral administration were lower in the long-term cigarette smoke-exposed group than in the control group. In the smoke-exposed group, the AUC and Ka were lower, and the Ke was slightly higher than in the control group. Liver weight and the ratio of liver weight to body weight were lower in the smoke-exposed group, and cytochrome b5 content and NADPH-cytochrome P-450 reductase activity were higher, but cytochrome P-450 content did not differ from the control group. These results indicate that long-term exposure to cigarette smoke suppresses theophylline absorption from the gastrointestinal tract, accelerates its elimination, and affects liver microsomal enzymes which metabolize drugs. PMID- 1304446 TI - Modification of liver and serum enzymes by paraquat treatment in rabbits. AB - Paraquat (PQ) is known to cause progressive interstitial fibrosis in the lungs. Previous investigations have indicated that PQ acts by lipid peroxidation of the membrane. However, there are few reports on the action of PQ on hepatic enzymes. This work was carried out to investigate the modulation of various hepatic enzymes by PQ in rabbits. Paraquat was administered at a dose of 3, 6 or 12 mg/kg b. wt/day intraperitoneally to male rabbits for different periods of time. Administration of paraquat resulted in a significant decrease in plasma activities of transaminase enzymes, alkaline phosphatase and liver transketolase. No significant change was found in the activities of plasma and hepatic lactate dehydrogenase and alkaline phosphatase. A marked increase in blood glucose was noticed 48 hours after paraquat administration. PMID- 1304447 TI - Tiaprofenic acid-induced photohemolysis in vitro is inhibited by nimesulide. AB - The effect of nimesulide on red blood cell (RBC) lysis photosensitized by tiaprofenic acid was investigated. The tiaprofenic acid-induced photohemolysis rate was enhanced by exposure to oxygen but lysis was also observed under anaerobic conditions. Photohemolysis was decreased by reduced glutathione (GSH) and reduced even more by butylated hydroxyanisole (BHA); sodium azide, superoxide dismutase and mannitol did not show a significant effect. Nimesulide did not cause any RBC lysis and inhibited this action of tiaprofenic acid by 20-30%, depending on the concentration of nimesulide and the intensity of ultraviolet A light. The protective effect of GSH, but not of BHA, was increased by nimesulide. Our findings suggest that free radicals are generated in this in vitro model of phototoxicity and are involved in the photoaggression to the red blood cell membrane, this effect being partially inhibited by nimesulide. PMID- 1304448 TI - Unaltered ibuprofen-induced faecal blood loss upon coadministration of moclobemide. AB - The influence of moclobemide on ibuprofen-induced faecal blood loss was investigated in 24 volunteers. The subjects were randomly assigned to one of two groups and received from day 1 until day 14 either moclobemide 150 mg t.i.d. (group A) or placebo t.i.d. (group B). On days 8-14, when moclobemide concentrations in group A were at steady state, all volunteers additionally received ibuprofen (600 mg t.i.d). From day 15 to 21, all subjects received placebo alone. Faecal blood loss (FBL) was quantified daily by the 51Cr-labelled erythrocyte method. As expected for ibuprofen, a significant increase in FBL during the second week of the study was observed. There was no difference in FBL between the two treatment groups (moclobemide or placebo). Similar FBL values were observed in both groups (group A vs B): during the first week the FBL values were (mean +/- SD) 0.40 +/- 0.23 ml/day vs 0.55 +/- 0.53 ml/day on days 1-3 and 0.40 +/- 0.21 ml/day vs 0.37 +/- 0.13 ml/day on days 4-7. The increase in FBL during the second week was comparable in both groups, with and without moclobemide (days 8-10: 0.78 +/- 0.59 ml/day vs 0.80 +/- 0.58 ml/day; days 11-14: 1.49 +/- 0.95 ml/day vs 1.28 +/- 0.62 ml/day). A decline in FBL was observed during the third week under placebo in both groups, but baseline values were not reached during the observation period. Again there was no difference between the two groups (days 15-17: 0.91 +/- 0.52 ml/day vs 0.92 +/- 0.47 ml/day; days 18-21: 0.74 +/- 0.30 ml/day vs 0.68 +/- 0.48 ml/day). No statistically significant interaction was found between week and type of treatment, indicating that no significant influence of moclobemide on the ibuprofen-induced faecal blood loss occurred. No notable pharmacokinetic interaction between moclobemide and ibuprofen was observed. Moclobemide plasma concentration-time profiles with and without concomitantly administered ibuprofen were superimposable. The results demonstrate that the concomitant administration of ibuprofen and moclobemide to healthy volunteers does not result in a clinically significant interaction, either at the pharmacodynamic (faecal blood loss) or at the pharmacokinetic level. PMID- 1304449 TI - Effect of anhepatic phase of surgery using veno-venous bypass technique on plasma fentanyl concentration. Report of two cases. AB - We administered fentanyl continuously and measured its concentration in plasma in two patients undergoing surgery which produced an anhepatic phase using the veno venous bypass technique; one patient had extracorporal liver resection and the other had venoplasty of the inferior vena cava and the right hepatic vein. The plasma fentanyl concentration increased during the anhepatic phase and decreased in the post-anhepatic phase in both cases. Though fentanyl has a wide safety margin, attention must be paid to such drug characteristics in the management of anaesthesia during the anhepatic phase. PMID- 1304450 TI - Heart in pituitary diseases. AB - Of hormones secreted by the pituitary, a direct effect on cardiac metabolism and function is exerted only by growth hormone (GH). Its chronic overproduction in adulthood leads to acromegaly. The main cardiovascular manifestations of acromegaly are hypertension and cardiac hypertrophy. The paper summarizes the results of clinical research into the "acromegalic heart" in an internationally unique group of 78 patients with acromegaly on long-term follow-up. Both clinical findings and experimental data available in the literature indicate that cardiac hypertrophy is due to a direct effect of GH on the myocardium. Hypertension occurs in 50% of patients, has the nature of volume hypertension and exerts only an additive effect on the development of left ventricular hypertrophy. Once GH overproduction has been eliminated, cardiac hypertrophy and hypertension can be reversed to a certain stage, a finding highlighting the necessity of instituting treatment of acromegaly as early and as vigorous as possible. PMID- 1304451 TI - Heart in thyroid diseases. AB - The paper examines the basic pathophysiologic mechanisms playing a role in the development of cardiovascular changes on thyroid hyper- and hypofunction. The haemodynamic changes typically associated with increased and decreased secretion of thyroid hormones are described and compared. Using echocardiography, the haemodynamics changes are documented in 12 patients with hyperthyroidism and 19 patients with myxoedema prior to thyrostatic and substitution therapy. Characteristic findings in florid hyperthyroidism include a significant rise in left ventricular end-diastolic volume as well as increases in stroke volume (SV) and cardiac index (CI). Mean velocity of circumferential fibre shortening (mVCF) is also significantly increased. Left ventricular myocardial weight shows a tendency towards an increase. Hypothyreosis is primarily associated with decreases in SV and CI; mVCF also declines. The paper underlines the importance of causative therapy as the above haemodynamics changes are fully reversible on attaining normal thyroid function. PMID- 1304452 TI - Heart in adrenal diseases. AB - The paper reviews the hitherto rather scarce literature concerned with cardiac changes in phaeochromocytoma, primary hyperaldosteronism and Cushing syndrome, and presents the authors' own echocardiographic findings in these diseases. In phaeochromocytoma they found a slight thickening of the interventricular septum which, however, did not fulfil the criteria of asymmetric left ventricular hypertrophy. Also other parameters showed higher values attesting to an increased left ventricular mass, however, without exceeding normal limits. Focal disturbances of left ventricular kinetics and the decrease in LV systolic function were non significant. The picture of obstructive hypertrophic cardiomyopathy, frequently mentioned in the literature, was observed only once, giving grounds to the suspicion that it is only a nonspecific manifestation of the hypercontractile state of the myocardium. In primary hyperaldosteronism only slight posterior LV wall thickening and an increase in the LV mass index were found, compared to control group. No significant changes were found in Cushing syndrome besides a tendency to concentric LV hypertrophy. Echocardiographic changes observed in all three affections disappeared after successful surgical or drug treatment. PMID- 1304453 TI - Left main coronary artery stenosis. AB - Between 1 January, 1989, and 28 April, 1990, a total of 888 selective coronary arteriographies were performed at the Institute for Clinical and Experimental Medicine in Prague. Of that number, 58 findings were assessed as at least 50% stenosis of the left main coronary artery (LCA). Having applied exclusion criteria, 50 patients (i.e., 5.63% of all those examined) were entered into a retrospective study. They were 45 men (90.0%) and 5 women (10.0%) with significant cumulation of risk factors for IHD; more than half on them had a history of coronary event. The patients had marked symptomatology--NYHA Class III and higher angina pectoris was present in 96%, a low tolerance of exercise was found in 26 patients undergoing ergometry (average workload of 13 kJ and heart rate of 111/min); exercise testing was invariably evaluated as positive. Coronary angiography regularly revealed multiple coronary artery lesions; the right coronary artery was also involved in 90%; a collateral circulation was present in as little as 34%. The localization of coronary stenoses and the mostly preserved left ventricular mechanical function allowed operative management of IHD in 84% of cases. In the group of patients undergoing surgery, hospital mortality was 4.8%. On long-term follow-up (mean 6.2 months) of the group of patients operated on, 59.9% were free of problem, 31% had NYHA Class II angina pectoris, and there was no improvement at all in one patient only (2.4%). In the group provided conservative therapy (not operated on primarily for severe left ventricular dysfunction), one patient died of recurrent myocardial infarction and cardiogenic shock, 2 have NYHA Class IV angina pectoris, and the remaining subjects continue experiencing NYHA Class III problems. PMID- 1304455 TI - Congenital pulmonary arteriovenous aneurysms. AB - The authors analyse their diagnostic and therapeutic experience with 26 patients suffering from congenital pulmonary arteriovenous aneurysms. Symptoms of the disease were found to depend directly on the presence and volume of arterial blood shunted into the venous bed. The volume of shunted nonoxygenated blood varied between 20 and 48 p.c.; the reflux caused hypoxic hypoxaemia with HbO2art. = 91.2 +/- 1.43%; pO2art. = 63.6 +/- 5.54 mmHg. Aimed tomography and pulmonary angiography proved most advantageous in terms of diagnostic; with their aid it was possible to identify three variants of congenital pulmonary arteriovenous aneurysm: isolated, multiple and "of the capillary haemangioma type". PMID- 1304454 TI - Sick sinus syndrome: strategies for reducing mortality. AB - The evolution of sick sinus syndrome is slow, and its clinical and electrocardiographic manifestations are intermittent. A-V and I-V conduction disturbances often arise, but incidence of defects with clinical consequences is too low. Death rate, when large groups are considered, is slightly higher than that of the general population of the same age and with similar pathologies. Mortality depends on concomitant pathologies, on the development of congestive heart failure, on the arterial thromboembolism and on the type of sinus disease. The use of ventricular pacemakers (VVI) did not reduce mortality. Atrial pacing (AAI) gives the auricles electrical stability preventing fibrillation and systemic embolism. The hemodynamic role of the auricles is also preserved. As a consequence, death rate is reduced when AAI is used. In cases with a-v conduction disturbances or with paroxysmal atrial fibrillation, dual chamber pacing (DDD) is preferable because it permits ventricular pacing to be continued even if a-v block or paroxysmal or chronic atrial fibrillation appears. When using ventricular pacing and in cases in which pacing is not considered, warfarin or aspirin can prevent strokes and systemic embolism. In bradycardia-tachycardia syndrome requiring treatment of arrhythmias dual chamber pacemaker must be implanted. PMID- 1304456 TI - Heart adrenoreactivity during acute haemic hypoxia. AB - The influence of acute haemic hypoxia of mild and moderate degree, produced by subcutaneous administration of sodium nitrite (25-30 or 50 mg/kg) supporting the blood haemoglobin production, on heart adrenoreactivity was studied in experimental rats. An intensified sympathoadrenal activity was detected, that manifested itself by a marked increase in adrenaline content in the hypothalamus, brain stem and heart. In analogous experiments performed in dogs, with increasing severity of hypoxia a decrease in arterial pressure and left ventricular pressure, increase in left ventricular end-diastolic pressure, and an impairment of myocardial contractile function were observed. Administration of adrenergic substances intensified the effector reaction in the heart. According to the authors' conclusions, experimental, hypoxia of the given model calls forth intensification of heart adrenoreactivity in warm-blood animals. PMID- 1304457 TI - Adenosine's role in the genesis of bradyarrhythmias induced by acute myocardial hypoxia. AB - A close or even causal relation between myocardial adenosine and bradyarrhythmias during acute myocardial hypoxia was testified in guinea pig, rabbit and dog mainly by using specific competitive antagonist and synchronous quantitative analysis of 3 variables: intensity of myocardial hypoxia, degree of endogenous adenosine increment and severity of bradyarrhythmias. Results disclosed: A) striking resemblance of the bradyarrhythmias with hypoxic origin to those caused by exogenous adenosine, B) same locality of A-V conduction block induced by both myocardial hypoxia and exogenous adenosine, C) precise parallelism among the above-listed 3 variables with very high correlativity (r = 0.99, P < 0.01), D) frequent accompaniment of reversal of hypoxic bradyarrhythmias through resupply of 21% O2 with normalization of preexisted increase in myocardial adenosine, E) satisfactory blockade of hypoxic bradyarrhythmias by adenosine's specific antagonist--aminophylline and their augmentation by adenosine's uptake inhibitor- dipyridamole, F) close similarity of the characteristic curve representing relation among the above 3 variables to that among intensity of myocardial hypoxia, degree of endogenous adenosine increment and amount of coronary blood flow in which adenosine's role as a mediator has been well documented and G) reproducible persistence of bradyarrhythmias during myocardial hypoxia irrespective of preliminary vagotomy and atropinization, denoting independence of the occurrence of such dysarrhythmias upon vagal drive, suggestive of a mechanism other than vagotonia. We advocated that hypoxia-induced bradyarrhythmias was caused by increment in endogenous adenosine. PMID- 1304458 TI - Longitudinal effect of captopril on aortic and arteriolar development in normotensive rats. AB - To explore the effect of chronic converting enzyme inhibition on the macro- and microcirculation, normotensive rats were chronically given 100 mg/kg/day of captopril in their drinking water beginning one day before uninephrectomy. Cremaster arteriolar dimensions were measured 2, 4, or 8 weeks later by intravital microscopy, before and after topical application of 10(-3) M adenosine. Mean blood pressure were significantly decreased at 4 (17%) and 8 (18%) weeks in treated rats vs age-matched control. Structural diameter reductions occurred in large arterioles starting 4 weeks in treated rats, and in small arterioles at 8 weeks. The cross-sectional wall area of large arterioles increased with age in control animal, but not in captopril treated one. Eight weeks of captopril treatment also decreased the cross-sectional wall area in small arterioles. Measured by stereological techniques, small arteriolar density decreased 17% at 4 weeks and 13% at 8 weeks in treated rats. Using histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in treated rats at 4 (24%) and 8 (15%) weeks without a significant change in internal diameter. PMID- 1304459 TI - Detection of antigens associated with lung carcinoma in sera by monoclonal antibodies WLA-2C4 and CL-3. AB - The levels of tumor-associated antigens (TAAS) corresponded to monoclonal antibodies WLA-2C4 and CL-3 in sera of 57 lung cancer patients, 100 healthy adults and 50 non-tumor disease patients were assayed with SABC-ELISA of immunobinding inhibition test. The threshold values of WLA-2C4 and CL-3 (RBI) were 12% and 36%, respectively. The positive results of lung carcinomas with at least one of the two TAAS were as follows: squamous cell carcinoma 89%; adenocarcinoma 83%; small cell carcinoma 67% and their mean positive rate was 79%. Whereas the positive rate in healthy adults and non-tumor disease patients was only 6%. These results indicate that using monoclonal antibodies WLA-2C4 and CL-3 simultaneously may be helpful to the serological diagnosis of lung carcinoma. PMID- 1304460 TI - Antitumor activity of psoralen on mucoepidermoid carcinoma cell line MEC-1. AB - Psoralen (PSO) was found cytotoxic against in vitro cultured human mucoepidermoid carcinoma cells of MEC-1 cell line. Its IC50 value was 8.6 micrograms/ml, and relative antitumor activity (RAA) 15. PSO suppressed DNA synthesis, damaged microvilli and cell membrane, and induced degeneration of mitochondria. It inhibited the growth of MEC-1 cells transplanted in nude mice by 79.1% which was as strong as pingyanmycin (PYM 81.4%). The body weight loss of PSO treated tumor bearing mice was 5%, whereas that of PYM treated ones 13.3% (P < 0.01). PSO may be an effective agent for the treatment of human mucoepidermoid carcinoma. PMID- 1304461 TI - Effect of hamster liver passage on the isoenzyme patterns of Entamoeba histolytica. AB - The effect of hamster liver passage on the isoenzyme patterns of isolates of Entamoeba histolytica was investigated. Three isolates, F, G and T were originally obtained from patients with acute amebic dysentery and another strain, C, was obtained from an asymptomatic carrier. All these strains were maintained for over two years in axenic culture. The isoenzyme pattern (zymodeme) of hexokinase (HK), phosphoglucomutase (PGM) and glucose phosphoisomerase (GPI) of these strains was found to belong to non-pathogenic group X, but the isoenzyme pattern of GPI resembled less pathogenic zymodeme XX and might be an intermediate type. Following inoculation of trophozoites into hamster livers and recovery after abscess formation, their isoenzyme pattern changed and revealed that they belonged to pathogenic type XIV. Liver passage caused an enhancement in amebic virulence as evidenced by their increased ability to destroy leukocytes. The results indicate that isoenzyme pattern is not a stable property of E. histolytica. PMID- 1304462 TI - Ultrastructural study of cerebral arteries in Moyamoya disease. AB - The cerebral arteries in seven cases of Moyamoya disease, demonstrated by angiography were observed by light, transmission and scanning electron microscopy. In two cases, the lumen of the terminal portion of the internal carotid artery was completely occluded by proliferated connective tissue. The characteristic pathologic change was extensive destruction of the smooth muscle cells and the elastica interna. Degeneration and necrosis of smooth muscle cells were obvious in the media. Many condensed organelles and other elements of cellular destruction were dispersed throughout the interstitium. The media was thinned. The proliferated smooth muscle cells in the intima showed the same destructive changes as in the media. The elastica interna was excessively infolded and was thickened or thinned, disrupted or disintegrated in some segments. Identical, but less severe and more localized changes were seen in three middle cerebral arteries (M2 and M5 segments) and two collateral arteries at the base of brain. These changes suggest that Moyamoya disease is a progressive disorder characterized by repeated destruction of smooth muscle cells occurRing over a long time period. The pathogenesis of these changes is discussed. PMID- 1304464 TI - Percutaneous debridement of complex pyogenic liver abscesses. AB - The author's approach and technique in the treatment of complex liver abscesses that persisted or recurred following percutaneous drainage are described. Six patients were treated by percutaneous debridement using an instrument specially designed for that purpose. Four patients were chronically ill but stable, while the other two were septic, hypotensive and considered to be life threatened. All patients had primary pyogenic abscesses. Four had demonstrated mixed bacterial flora consisting of E. coli, Klebsiella, Proteus and gram-positive cocci and two were caused by E. coli only. Contrast enhanced CT of the abdomen in all cases revealed multiloculated or septated abscesses containing large central debris and peripheral shell or halo of compromised hepatic parenchyma. Debridement was successful in all cases, resulting in complete healing within 12 days. Follow-up for 1-4.5 years revealed no recurrences. Three cases of infected tumors of the liver were referred for treatment. CT findings in these cases demonstrated a well developed external capsule and internal septations, and the absence of a surrounding halo of compromised parenchyma distinguishes them from primary abscesses. This preliminary experience makes the authors to conclude that percutaneous debridement of pyogenic liver abscesses is a safe and curative procedure in selected cases of life-threatening chronic liver abscesses. PMID- 1304463 TI - Prospective double-blind study of CEE3 in peri- and postmenopausal women: effects on bone loss and lipoprotein lipids. AB - A prospective double-blind study was carried out in 136 women 0.5 to 21 years since menopause (YSM) in order to demonstrate the effects of a long-acting estriol derivative-Nylestriol (CEE3) on bone loss and lipoprotein lipids. They were orally administered at 2 mg of CEE3 or placebo every 2 weeks. Among 90 subjects who finished 1 year of medication, 49 received CEE3 and 41 placebo. The results were: 1. Serum ALP, Ca/Cr and Hop/Cr in fasting urine decreased in 3 months (P < 0.05); 2. Menopause-related reduction of forearm bone density was restrained; 3. LDL-C decreased in 3 months and HDL-C increased in 6 months (P < 0.05), with no significant changes in TC and TG; 4. Side effects were mild. 1/3 of those with intact uterus had spotting and another 1/3 had moderate withdrawal bleeding after the addition of medroxyprogesterone acetate at the end of 12 months of CEE3 therapy. This study demonstrates that CEE3 is effective and acceptable for preventing osteoporosis and lipoprotein lipids disorder in postmenopausal women. Long-term application awaits further studies. PMID- 1304465 TI - Endoscopic management for traumatic occlusion of posterior urethra. AB - When traumatic posterior urethral transection occurs with serious pelvic fracture, the patient is usually under severe hemorrhagic shock and multiple injuries. It is of prime importance to treat shock and the associated injuries promptly. As for the urethral disruption a simple suprapubic cystostomy at the moment is preferred. Occlusion of the posterior urethra would eventually appear and can be managed endoscopically 3-6 months later. Fifteen such cases were thus managed from 1984 to 1990 with an improved endoscopic technique with a success rate of 93.3% (14/15). The advantages of this technique and the merits and demerits of various primary urethral reconstruction procedures are discussed. PMID- 1304466 TI - Effects of discectomy on the stress distribution in the lumbar spine. AB - The change of the stress distribution of the lumbar spine after discectomy was analysed by the three-dimensional finite element method. It was shown that the stress level in the posterior element was higher, but that in the anterior element was lower than before disc excision. The most significant change of the stress distribution was found in the trabecular bone of the vertebral body. It is considered that in discectomy the normal disc tissue should be preserved as much as possible to maintain good function of the spine. PMID- 1304467 TI - Comparison of two pain rating scales among Chinese cancer patients. AB - The Simple Descriptive Scale (SDS) has been known to be easier to use, but lacks sensitivity when compared to the Visual Analogue Scale (VAS). In this study, 79 cancer patients quantified the intensity of their pain experience on both the VAS and SDS before receiving pain therapy and on the fifth day after commencing the therapy. High correlations were observed between the two scales in age, sex and types of analgesics. The results demonstrate that the SDS provides a simpler and, perhaps, equally sensitive alternative to the VAS, in measurement of cancer pain among Chinese patients. It would be particularly useful for those with language barriers and/or other factors in understanding the requirements or the VAS. PMID- 1304468 TI - Hemodynamic effects and the effective treatment of naloxone on experimental acute pancreatitis in dogs. AB - Dog model of acute pancreatitis, induced by intrapancreatoductal injection of fresh trypsin-bile mixture, was used to investigate the effects of naloxone on hemodynamic changes in acute pancreatitis. In the control group, acute pancreatitis was induced and characterized hemodynamically by the decrease in maximum positive and negative dP/dt (+/- dP/dtmax), cardiac output (CO) and cardiac index (CI), and increase in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVP), as well as early reduction of pancreatic blood flow (PBF). In the naloxone treated group, naloxone was given intravenously 10 minutes after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80 micrograms/kg/h for 3 hours). It was found that naloxone significantly increased PBF and the +/- dP/dtmax effectively prevented the significant decrease in CO, CI and increase in PVR, SVR observed in untreated acute pancreatitis; and significantly reduced the severity of pancreatitis, as assessed by both histological staging and mortality rate. These results suggest that naloxone appears to limit the progression from edematous to hemorrhagic pancreatitis through preserving PBF and improving systemic hemodynamics at the early phase of acute pancreatitis; hence the hypothesis that endogenous opioid peptides may play a role in the pathophysiology of acute pancreatitis. PMID- 1304469 TI - Sturge-Weber syndrome without facial nevus. PMID- 1304471 TI - [Esophageal cancer in rhesus monkeys from the Taihang Mountain area. A preliminary report]. AB - 124 Rhesus monkeys (Macaca Mulatta) were caught in the Taihang Mountain region, a high incidence area of human esophageal cancer in Northern China, in January 1989. Among them, two monkeys died of esophageal carcinoma in 1990. Case 1, a male monkey about 6.5 years old and weighing 14.5 kg, had symptoms of salivation, vomiting and dysphagia in February 1990. The symptoms became gradually more serious and died in March 1990. Postmortem examination revealed a huge tumor in the distal segment of esophagus, causing severe stricture of the organ. The tumor was classified as medullary type and histopathologically diagnosed as a well differentiated squamous cell carcinoma, with metastases to mediastinum and lymph nodes of right gastric group. Case 2, a female monkey about 11-year-old and weighing 10.0 kg, showed loss of appetite, tiredness, somnolence, coughing and vomiting in September and died in December 1990. Autopsy revealed an annular tumor involving the whole circumference of lower portion of the esophagus. The tumor was of ulcerative type and diagnosed as a well differentiated squamous cell carcinoma. The symptoms and pathological changes of the two monkeys showed high similarity to esophageal cancer in humans. We believe that the present findings would provide important leads for further study to clarify the etiology and pathogenesis of human esophageal cancer in this high incidence area of esophageal cancer. PMID- 1304470 TI - [Exposure level of N-nitrosamines in the gastric juice and its inhibition by vitamin C in high risk areas of esophageal cancer]. AB - A total of 391 gastric juice samples was collected from Ji Yuan and An Shi counties, high and medium risk areas of esophageal carcinoma in Henan province. NDMA, NDEA, NMBzA, NPip and unknown compounds were assayed in the fasting gastric juice. Among these nitrosamines, NMBzA, NPyr and NPip were specific in inducing esophageal cancer in animals. The amount of nitrosamines in the gastric juice collected from Ji Yuan county was higher than that from An Shi county. The exposure level of nitrosamines of subjects from these two localities were significantly different (P < 0.001). There was a positive relationship between the nitrosamines exposure level and esophageal cancer mortality rate. The amount of gastric N-nitrosamines from An Shi subjects as treated with vitamin C was reduced. It is evident that vitamin C can inhibit N-nitrosamine formation in the stomach, thereby, reducing the N-nitrosamines exposure level. PMID- 1304472 TI - [Minimum residual leukemic cells in genetically marked brown Norway rat myelocytic leukemia model]. AB - Different methods were used to detect minimal residual leukemic cells (LT 12 nl), which had been genetically marked with E. coli 1 acZ and neo-gene by retrovirus vector mediated gene transfer. The detection levels of flow cytometry based FDG staining and fluorophotometric method based MUG staining were 10(-3) to 10(-4) and 10(-2) to 10(-3), respectively. The method of G 418 selective agar culture was demonstrated as a 10(-4) to 10(-5) levels for the detection of LT 12 nl residual leukemic cells in bone marrow. The results indicated that the selective agar culture can be used as a sensitive method for the study of minimum residual disease in the BNML leukemia model. We have used the selective agar culture to study the distribution of clonal LT 12 nl cells in BNML during minimum residual disease (MRD). A heterogenous distribution pattern of the clonal leukemic cells was found in the genetically marked BNML leukemia model during the MRD phase. PMID- 1304473 TI - [Effects of parenteral nutrition on cell cycle kinetics in gastric cancer patients]. AB - Studies were made on tumor growth changes by 1-week supplementary parenteral nutrition in undernourished advanced gastric cancer patients. Biopsy of the normal mucosa and cancerous tissue were taken through endoscope before and one week after parenteral nutrition and at the time of operation. Percentage of cells in various phases were analyzed by flow cytometry. The frequency of S and proliferative phases were markedly increased (P < 0.05) in cancerous tissue but not in the normal mucosa. These results demonstrate that a stimulating effect may be present in tumor cell kinetics and hence, the use of a cycle-specific chemotherapeutic agent is indicated. PMID- 1304475 TI - [Intracellular bile acid activities in colon cancer and normal colon mucosa]. AB - Bile acids are thought to be involved in the etiology and development of colo rectal cancers. In this study, the intracellular bile acid activities both in colo-rectal cancers and normal colo-rectal mucosa in 12 patients were measured with a new bile acid ion selective microelectrodes. The results demonstrated that bile acid activities of colo-rectal mucosa cells were 5.0 +/- 3.7 x 10(-5) mol/L and those in colo-rectal cancer cells were 17.6 +/- 9.6 x 10(-5) mol/L, which is three times as high. This demonstrates that bile acids are closely related to the development of colo-rectal cancers. The intracellular bile acid activities remain stationary with age and sex. PMID- 1304474 TI - [Relationship between Langerhans cells and prognosis of patients with gastric carcinoma]. AB - Langerhans cells (LCs) in 73 cases of gastric carcinomas (GC) were quantitatively investigated by ABC immunohistochemical method using anti-S-100 protein antibody. The mean density of LCs (cell numbers/mm2) infiltrating the carcinomas showed an intimate relationship with the prognosis (P < 0.01) and the status of lymph node (LN) metastasis (P < 0.05). The density of LCs in patients without LN metastasis was significantly higher than that with LN metastasis. In 73 cases of GC, there were 35 cases of LCs(+) and 38 of LCs(++) groups. The mean survival times were 29.81 months in the former and 52.21 months in the latter. A significant relationship (P < 0.05) between the survival and degree of the density of LCs was showed by Student's t test and life table method. There were no correlation among the density of LCs and gross appearance, depth of invasion, histologic type and patients' sex. The fact indicated that LCs may play an important role in immunological defense mechanisms of host against the tumor. Patients with dense infiltration of LCs survived longer and showed less LN metastasis than those without such an infiltration. It is considered that measurement of LCs in specimens of GC may be taken as one of criteria of prognosis. PMID- 1304476 TI - [Clinico-pathologic studies on 143 cases of tonsillar malignancies with special reference to lymphomas]. AB - 143 cases of tonsillar malignancies consulted or treated in our hospital during the past 33 years (1958-1991) were studied morphologically and histochemically. There were 126 non-Hodgkin's lymphomas (NHL), 14 squamous cell carcinomas and one each of mucoepidermoid carcinoma, malignant melanoma and histiocytic lymphoma. The results showed that: 1. The ratio of peripheral T-cell and B-cell lymphoma was high (2.08:1), of which the reason is unexplained, 2. Many tonsillar NHLs had been misdiagnosed as undifferentiated carcinomas, poorly differentiated carcinomas or reticular cell sarcomas in the past, and 3. Most of the B-cell lymphomas belong to the high grade malignant large cell lymphomas, like the large non-cleaved and immunoblastic type. These findings are different from what is generally believed and known. PMID- 1304477 TI - [Study on prophylactic hypoxyradiotherapy to whole abdomen and pelvis]. AB - In cancer radiotherapy, an enormous radical dose may be necessary. However, it is sometimes limited by the tolerance of the surrounding normal tissues. Transient systemic hypoxia induced by breathing 10.5% oxygen gas during radiotherapy may protect the normal tissues. In the prophylactic irradiation to the whole abdomen and pelvis for the NHL or ovarian cancer, clinical radiation responses were distinctly mild and occurred later in the hypoxyradiotherapy group. Micronucleus frequency of the peripheral lymphocytes was taken as the criterion in estimating the radiation effect. A radioprotective factor (RPF) of 1.52 was obtained. PMID- 1304478 TI - [Diagnosis and surgical treatment of 103 early cases of cancer of the esophagus and gastric cardia]. AB - From April 1986 to February 1992, 103 cases of early cancer of esophagus and gastric cardia were detected by the occult blood detector and fiberoptic gastroscope in Yangzhong County, Jiangsu province, a high incidence region of these cancers. All cases were confirmed by operation and pathology. Fourty-seven had cancer of the esophagus and the rest cancer of the gastric cardia which accounted for 17.1% (103/604) of the surgically treated cases in the same period. The authors believe that most patients with early lesions of these cancers are not asymptomatic. Periodic screening of the general population in the high risk area by the occult blood detector is indicated not only for the people themselves but also for improvement of the medical works as well. PMID- 1304479 TI - [Primary chondrosarcoma of the lung]. AB - Five cases of primary chondrosarcoma, a rare tumor of the lung, are reported. The diagnosis should be made by pathology. Some conditions should be ruled out: 1. tumor from the chest wall, 2. chondrosarcoma of bone discovered after operation, 3. ovarian teratoma found prior to operation, 4. patient with history of hamartoma of the lung, and 5. atypical pathology. Pathologic subtyping is not prognostic. The main cause of death was intralobar spread. It never gives rise to extrathoracic metastasis and should be treated by surgery. PMID- 1304480 TI - [Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)]. AB - Primary neuroendocrine carcinoma of the skin (Merkel cell tumor), a rare malignancy originating from the skin, has only been established in the recent years. It has a main predilection on the skin in the head and neck region with an obvious tendency of local recurrence and early metastasis. Histopathologically, it resembles the neuroendocrine carcinoma from other sites of the body in morphology, immunohistochemistry and ultrastructure. Diagnosis of this tumor is quite difficult. Based upon two of our cases as verified by electron microscopy and/or immunohistochemistry, the clinical and pathological features of this tumor are described and the literature reviewed. PMID- 1304481 TI - [Microwave treatment of 20 patients with oral cancers]. AB - Twenty patients with oral cancers were treated by microwave alone from October 1989 to December 1990. There were: 7 cancer of floor of mouth and 13 cancer of the tongue. After treatment, pathology all turned negative. The patients were followed up for 9 to 24 months with all the primary lesions controlled. The functions and cosmetic results were perfect. Complications included edema of local tissue and bleeding. To prevent bleeding after microwave treatment, ligation of the ipsilateral external carotid artery should be done. To prevent dyspnea, tracheostomy should be done in patients with cancer of the root of tongue. Effect of microwave coagulation is best achieved by the interstitial technique. For lymph node metastasis, radical neck dissection should be done after the edema of the primary lesion subsides. PMID- 1304483 TI - [An evaluation of radiofrequency current catheter ablation in the treatment of paroxysmal tachycardia]. PMID- 1304482 TI - [Clinical trial of China-made carboplatin in advanced ovarian cancer--an analysis of 53 cases]. AB - Fifty three patients with evaluatable ovarian cancer were conducted a clinical trial of a new antineoplastic drug, carboplatin (cp) made in China. Apart from 1 case of stage Ic and 3 cases of stage II, all the remainders had advanced disease including stage III, IV or recurrences, and mainly consisting of epithelial carcinoma (44 cases). Thirty two patients were treated with single cp at the dose of 260-410 mg/m2 and twenty one were treated with combination chemotherapy of cp at a dose of 180-350 mg/m2 plus adriamycin and cyclophosphamide by intravenous infusion without hydration, repeated every 4 weeks, 2-4 courses. The response rate was 56% (18/32) and 48% (10/21), respectively. There were obviously different response rates in patients with previous chemotherapy (25% and 23% in cp single and combination chemotherapy groups) and without chemotherapy (67% and 88% in single and combination groups). It showed that cp was effective in treatment of ovarian cancers with advantages that gastrointestinal reaction was less severe in cp group than in the group using drugs including cis-platin, and no renal toxicity. However, cp showed more marked myelosuppression and hepatic injury in small number of the patients. PMID- 1304484 TI - [A critical evaluation of the cardiac arrhythmia suppression trial study]. PMID- 1304485 TI - [Cardiac arrhythmia suppression trial]. PMID- 1304486 TI - [Clinical application of radiofrequency ablation]. AB - I. Radiofrequency ablation of atrioventricular accessory pathway in patients with WPW syndrome: Seventeen accessory pathways in 15 patients with Wolff-Parkinson White syndrome (WPW) were ablated with radiofrequency current. There were 15 accessory pathways located on the left side of the heart (12 left free wall, 1 posterioseptal, 1 posteriolateral and 1 midseptal) and 2 pathways on the right side (1 right free wall, 1 anterioseptal). 16 accessory pathways (94.1%) in 14 patients were permanently abolished. Plasma CK-Mb, SGOT and LDH increased moderately in 7 cases (46.7%) and decreased to normal level in 3-4 days. CONCLUSION: catheter ablation of accessory pathways with radiofrequency current is a safe and effective therapeutic method for patients with refractory tachycardias mediated by these pathways. II. Radiofrequency ablation of slow pathways to cure AV nodal reentrant tachycardia: Radiofrequency energy was used to selectively ablate the slow pathways in 8 patients with atrioventricular nodal reentrant tachycardia. The slow pathways in all 8 cases were ablated successfully and no episodes of tachycardia could be induced. The A-H, H-V interval and P-R interval of ECG did not change significantly. The Wenckebach points of atrioventricular node remained unchanged. The effective refractory periods of the fast pathways were shortened in 3 and prolonged in 5 cases after the procedure. There were no severe complications. No tachycardia recurred during the follow-up period between 2 weeks and 7 months. PMID- 1304487 TI - [Radiofrequency ablation of left-sided atrioventricular accessory tract to treat supraventricular tachycardia]. AB - Eleven procedures of radiofrequency catheter ablation of left-sided atrioventricular accessory tract were performed in 10 patients with atrioventricular reentry tachycardia aged 13-57 (32.7 +/- 13.2) years old. 10 patients, 9 with overt preexcitation syndrome and 1 with concealed bypath tract, had paroxysmal supraventricular tachycardia refractory to drugs for 1-31 (7.8 +/- 9.8) years. The ablation was succeeded in 9 cases (90%). The accurate localization of the accessory tract and the operating skill of ablation electrode were the key factors of success in ablation and reducing exposure to x-ray. PMID- 1304488 TI - [Preliminary experience in radiofrequency ablation of left-side atrioventricular accessory reentrant tachycardia]. AB - Left side atrioventricular accessory reentrant tachycardias (AVRT) were ablated in 25 cases. The pathways were 5 (20%), 15 (60%) and 5 (20%) in left anterior, lateral and posterior wall respectively. Accessory pathway potentials (AP) were recorded in 16 (64.0%) cases. Most APs were recorded on the anterior side of the earliest atrium activation (EAA). The atrial side of accessory pathway is anterior to the ventricular side. The V and A wave were almost confused on the local area of successful ablating, and the average VA time is 35.5 +/- 7.8 ms, and in those cases whose VA time was less than 30 ms was 48%. The power of successful ablating is 36.9 +/- 6.0 W, the current is 0.58 +/- 0.1 A, impedance is 110.3 +/- 11.9 omega. The area of accessory pathway could be detected accurately through the findings of AP and EAA. PMID- 1304489 TI - [4 cases of automatic implanted cardioversion defibrillator (AICD)]. PMID- 1304490 TI - [3 cases of left accessory pathway with tachycardia treated by radiofrequency ablation]. PMID- 1304491 TI - [Transcoronary chemical ablation of ventricular tachycardia after mapping of the arterial blood supply to the arrhythmogenic area (report of 2 cases)]. AB - Transcoronary chemical ablation of ventricular tachycardia was performed in 2 patients with refractory ventricular tachycardia in Fu Wai Hospital. The procedures were successful. 1.5 ml sterilized ethanol (95%) was given to 1 patient and 0.8 ml to the other. The 2 patients were cured and no arrhythmia was found during 32-months and 4-months follow-up period respectively. One patient developed a limited inferior wall myocardial infarction after 1.5 ml ethanol. No other complications were observed. We found that after careful transcoronary mapping with saline and antiarrhythmic drugs, chemical ablation could prevent further episodes of the arrhythmia in selected high risk patients. PMID- 1304492 TI - [Local features of electrophysiologic and epicardial mapping of posterior septal accessory pathways in patients with surgically corrected preexcitation syndrome]. AB - Posterior septal accessory pathways were documented in 6 patients with preexcitation syndrome who underwent detailed electrophysiologic evaluation and epicardial mapping. All 6 patients were cured by surgical ablation of accessory atrioventricular pathway. After follow-up of 9 months on average, 6 patients remain cured. No patient had recurrent supraventricular tachycardia and none had persistent atrioventricular conduction disturbance. The results of electrophysiologic study and epicardial mapping showed local characteristics of posterior septal accessory pathways. Accurate localization of posterior septal accessory pathways is very important in raising the rate of success in operation. PMID- 1304493 TI - [A case report of ventricular tachycardia treated by radiofrequency ablation]. PMID- 1304494 TI - [Surgical treatment of abnormal myocardial bundle in the right ventricle]. AB - Thirteen cases of the anomalous right ventricle muscle bundle diagnosed during operation were reported. This is a rare congenital cardiac anomaly. It may be associated with other congenital anomalies, most commonly with ventricular septal defect and pulmonary stenosis but may also be isolated lesions. It exhibits no typical clinical findings. The preoperative misdiagnostic rate was high. Emphasis was on its intracardiac anomaly, some recognizable signs and anatomic relation during the operation. PMID- 1304495 TI - [The effect of open heart surgery on human cellular immunological function]. PMID- 1304496 TI - [Analysis of familial aggregation of serum lipids]. AB - Twin model was studied to explain the familial aggregation of serum lipids by correlation analysis between different kinds of relatives. The phenomenon of familial aggregation was shown existing in the findings of serum cholesterol, HDL Ch and LDL-Ch. Both effects from genetic and environmental factors were found. It is likely that there was maternal effects on cholesterol and LDL-Ch levels. The familial aggregation for TG was not very clear shown in this paper. Further study on genetic epidemiology of serum lipids is expected. PMID- 1304497 TI - [A study of the internal diameter of pulmonary artery in tetralogy of Fallot by 2 dimension echocardiography]. PMID- 1304498 TI - [A study of immunocompetence of peptide hormones in human pericardium]. AB - With RIA/HPLC and immunohistochemistry, the presence of angiotensin(A) and atrial natriuretic factor-like materials (ANF-LMs) was demonstrated in the pericardium of human and rats; the distributions of AII and ANF-LMs were found to be identical; AI was more than AII; renin activity was detected in the pericardium. There were three molecular forms of ANF-LMs in the pericardium. Mesothelial cells were the principal endocrine-secreting cells. AII and ANF-LMs of the pericardium were significantly increased in rheumatic heart disease. There were no correlations between plasma AII, ANF, urine AII, ANF and pericardial AII, ANF (P > 0.05). The data reported showed that the pericardium may have endocrine function under normal and abnormal conditions (heart failure) of the heart, in addition to its known mechanical properties. PMID- 1304499 TI - [Protective effects of gradual restoring of calcium on working rat hearts with ischemia-reperfusion injury]. AB - The effects of gradually restoring calcium concentration in initiating reperfusion on cardiac function, coronary blood flow and myocardial calcium content during reperfusion following global ischemia have been observed in isolated working rat hearts. The results showed that gradually restoring calcium reperfusion facilitated the recovery of the contracting relaxing and pump functions as well as coronary blood flow, and decreased the occurrence of arrhythmias during reperfusion and myocardial calcium content after reperfusion. The mechanism of the protective effect of gradual calcium restoration on the hearts was probably due to the inhibition of calcium overload in cardiac cells. However high calcium reperfusion deteriorated cardiac function. PMID- 1304500 TI - [An experimental study of evaluating regional left ventricular systolic function and global left ventricular pumping function by 2-dimension echocardiography]. PMID- 1304501 TI - [The influence of ventricular activation--contraction sequence on heart function]. PMID- 1304502 TI - [Colonization with group B streptococcus in pregnant women taken into the care of unit K and hospitalized in the department of obstetric pathology]. AB - Colonization with group B streptococci (GBS) in 714 pregnant women was investigated. Among 232 were hospitalised in department of pathological pregnancy and 512 were under ambulatory control. In 13.4% of hospitalised patients and 2.8% healthy pregnant women the colonization of vagina or throat with GBS was stated. The greatest percentage of vagina colonization was found in patients hospitalised in connection with gestosis or because of abortions, premature delivery and inanimate fetus. No correlation was found between range of GBS colonization and trimester of pregnancy. Almost all GBS strains proved to be susceptible for commonly used antibiotics but resistant to biseptol (88.2%). Patients of hospitalised group were more often colonized not only GBS but also other potentially pathogenic microorganisms. PMID- 1304503 TI - [Behavior of SCC marker level in cervix erosion, cervix dysplasia and cervical pre-invasive carcinoma]. AB - The work presents the results of studies on the behaviour of SCC antigen in 52 patients aged 21-70 years, with pathologic changes involving the uterine cervix and classified to the groups of erosion, dysplasia and carcinoma in different stage of advancement. The SCC antigen was determined in patients blood sera by radioimmunologic method, on the basis of Abbott Firm testes. An increase in concentration was observed exceed the norm (2 ng/ml) in cases of CIN and CIS. The rise of marker depended on the stage of the neoplastic process advancement in the uterine cervix. PMID- 1304504 TI - [Plasma fibrinolytic activity after gynecologic surgery]. AB - Fibrinolytic activity and fibrinolytic potential has been estimated in women submitted of gynecologic operations. Results was referred to age, extension of the operation and character of illness. Elevation of fibrinolytic activity immediately after operation and fibrinolytic potential five days later have been stated. PMID- 1304505 TI - [Prostaglandins PGF2alpha in the fight against bleeding and hemorrhage the uterus during the climacteric period]. AB - This article is about usage prostaglandins to fight against bleeding and haemorrhage from uterus in climacteric period. Prostaglandins are used widely by gynecologist and obstetrics as most powerful contracting drugs, namely in this situations when we observe returning, plentiful bleeding from uterus. Women with climacteric bleeding had administer prostaglandins intravenous or immediate intra cervix. They are very good drug, strongly and a long time hold up bleeding. This method give us time to better preparing patients to operation and diminish losses of blood. Side effects are small and not trouble. Prostaglandins are very simply in usage and characterise very good haemostatic effect, recognised faster then in typical methods like hormonal, mechanical antifibrinolytic etc. PMID- 1304506 TI - [Cystectomy accompanied by immediate examination as the preferred method of treating fibrocystic breast disease]. AB - Dysplasia benigna is the most often diagnosed women's breast disease. Among the 388 cysts operated patterns being presented at this work, 22 cases were considered to be the breast cancer by the emergent examination. The chosen therapy was cystectomy accompanied by the immediate examination. This seems to be the most certain therapeutic advance. PMID- 1304507 TI - [The value of combined examinations (ultrasonography, mammography and fine needle biopsy) in the diagnosis of breast diseases]. AB - 576 women have been examined towards breast lesions since 1987. Ultrasonography, mammography and fine needle biopsy were done in 353 patients. 63 women were advise to undergo surgery. The rest women were followed-up every 3-4 month. Combined methods comprising ultrasonography, mammography and fine needle biopsy were consistent with the histological assessment of the material taken during the surgery. PMID- 1304508 TI - [The significance of colposcopy in surgical gynecologic emergent situations]. AB - There has been described the case of coexistence of ruptured extra-uterine cysts and cancer of cervix uteri diagnosed by preliminary colposcopic examination confirmed by cytology and the directed biopsy specimen what enabled simultaneous surgical treatment. The presented paper is sufficient example that the colposcopy protects a woman requiring surgical treatment caused by the emergent gynecologic reasons from further surgical interventions in cases of simultaneous malignant changes of cervix uteri. PMID- 1304509 TI - [Clinical study on the contraceptive effectiveness of trisiston from the Jenapharm firm]. AB - Now triphasic contraceptive preparations are used widely. Some news low dose formulations are available on the market, among them Trisiston. The study was conducted to confirm clinically acceptance and effectiveness of Trisiston. There were 437 volunteers mostly multiparous, with a mean age of +/- 25 years who participated in a multi center study. They were taking pills for a 3 to 12 cycles. Cumulatively 4026 cycles were observed. The investigation was conducted according special protocol. At the admission a complete medical history was obtained and a general physical and gynecological examination was performed. All subject were controlled every 3rd month included laboratory tests (blood levels of Hb, WBC, RBC, ESR, carbohydrate metabolism, clotting factors, bilirubin, creatinine, protein, glucose, albumin, LDL, HDL). There was no case of pregnancy. Pearl index = 0. The Trisiston was well tolerated by most of women (80%). Some effects like headache, vertigo, mastalgia, spotting and breakthrough bleeding, loss of libido, premenstrual syndrome were observed in 20% patients, soma of our patients (20%) discontinued contraceptive. PMID- 1304510 TI - [Prognostic factors in patients with ovarian cancer]. AB - 350 patients with ovarian cancer were operated and irradiated postoperatively in the Center of Oncology in Krakow. 5-year survival with no recurrence was 41.7% (I.--77.3%, II.--44.1%, III.--7.7%). Stage, histological grade and residual volume tumor appears to be an important prognostic factors. PMID- 1304511 TI - [Effect of a mechanical insufficiency of lymph outflow from the uterus on the course of pregnancy in rats under experimental conditions]. AB - For lack of literature data studies of disturbed lymph outflow on pregnancy and foetus development in rats were accomplished. The studies were carried out on matured female inbred Wistar rats. In experimental group a mechanical insufficiency of lymph outflow from pregnant uterus was performed by means of ligature of lymphatics and excision of regional lymph nodes (i.e. lumbar, sacral and renal lymph nodes). The control groups were sham-operated and normal pregnant animals. Surgical procedures were performed at first day of pregnancy (determined by means of spermatozoa presence in vaginal smears). Animal were examined on 7th and 17th day of pregnancy and at delivery. The results from sham-operated group were identical with normal pregnant animals. In experimental group of 17th day of pregnancy was a lower number of foetuses, greater total number of resorption places, lower mean weight of placenta and foetus, higher mean placental-foetal ratio and longer duration of pregnancy compared with control groups. In delivery group it was obtained a lower mean weight of a new-born rat than in control group. The difference between values obtained in experimental group and values obtained in control group had a statistical significance. The estimation of obtained results allowed to draw a conclusion: the mechanical insufficiency of lymph outflow from uterus can has a negative influence for course of pregnancy and development of foetus in rats. PMID- 1304512 TI - [Induction of labor by using PGE2 and oxytocin in high risk pregnancies]. AB - The study group consisted of 82 primigravid and 55 multiparous women with post term pregnancy, preeclampsia, intrauterine growth retardation, insufficiency of placenta and diabetes mellitus have induced labor. Prepidil (Upjohn) in dosage 0.5 mg was given into uterine cervix of 46 patients (PG group) and oxytocin was infused to 42 patients in dosage ranged from 5 mU/min to 30 mU/min (Ox group). Induction of labor has been considered as successful, if after 12 hours of drug administration, regular contractions of uterus and dilation of cervix more than 3 cm were obtained. Significant improvement of cervix state, measured by Bishop score has been observed only in PG group, even if the induction of labor failed. Similar rates of caesarean sections and the same occurrences of late and variable decelerations have been observed in both study groups. Results obtained in both these groups suggest that induction of labor in such pregnancies after prostaglandins administration is more effective than oxytocin infusion. PMID- 1304513 TI - [Use of mid-arm and head circumference to estimate gestational age and nutritional status of newborns]. AB - 1110 neonates, from 30 to 42 of estimated gestational age (EGA) were measured on the 1st day of life to estimate upper mid-arm circumference (MAC) and head circumference (HC). Individual MAC/HC ratio was calculated. MAC/HC ratio was used to estimate gestational age and nutritional status of the newborns. We proved that MAC/HC ratio increased linearly between 30 and 38 week of pregnancy and it stabilized between 38-42 week. We compared MAC/HC ratio with birth weight, skin fold score, and ponderal index. We concluded that this ratio may be very useful to estimate gestational age and to include the neonates to "the group of risk". PMID- 1304514 TI - [Immunologic reaction differences of non-histone chromosome proteins (NHCP) in myometrium and leiomyoma of the uterus in women]. AB - Immune sera against non-histone chromosomal proteins (NHCP) of myometrium and leiomyoma were raised in our laboratory in rabbits after injection with purified antigens. (NHCP) were extracted 0.35M NaCl from 6 myometrium and leiomyoma tissue samples. Sera contained precipitating and non-precipitating antibodies reacting in Ouchterlony and ELISA tests with homologous and heterologous antigens. Serum against leiomyoma NHCP reacted higher extinction values with myometrium than with homological antigens. NHCP tissue concentration (mg/g) was higher for myometrium in spite NHCP/DNA ratio bigger for leiomyoma. Above mentioned results indicate antigenicity alterations of leiomyoma tissue when compared to normal myometrium of woman uterus. PMID- 1304515 TI - [Importance of prolactin level indication in detection of Sheehan syndrome]. AB - Prolactin (PRL) levels were studied in 5 women with Sheehan syndrome before and after metoclopramide (MCP, 10 mg i.v.) and domperidone (MOT, 10 mg i.v.) stimulation. The levels of PRL were measured by RIA method. The obtained results were compared with control group (10 female volunteers). Decreased serum level of PRL was found in 3 women before stimulation in comparison with control group. The highest serum concentration of PRL was found 30 min after MOT and MCP injection. In group of women with Sheehan syndrome the level of PRL was not significantly increased in MCP-test. In MOT-test the level of this hormone did not change. The findings of the present investigation suggest that measurement of PRL serum levels in MOT-test could be of value in early diagnosis of Sheehan syndrome. PMID- 1304516 TI - [Urinary stress incontinence and equilibrium of the genitourinary tract in village women]. AB - This study was performed in 100 women aged 28 to 60 years, who had 1 to 6 physiological deliveries. The women were divided into two groups: 1) living in cities; 2) living in villages. The number of deliveries, miscarriages, birth weight of fetus and retention of urine were recorded. Bacterial cultures were also performed and the statics of the genitourinary system was investigated. The amount of urinary retention was standardized using a 3 degree scale. It was found that women living in village significantly less frequently demonstrate changes in the statics of the genitourinary system, urinary stress incontinence and retention, as well as infections of the urinary tract. PMID- 1304518 TI - [Urinary steroid profiling in postmenopausal women (preliminary notes)]. AB - Urinary steroid profiling by means of Capillary gas chromatography in postmenopausal women was detected. Glass capillary columns, OV-1, were used. Our results show that there is a rise of extraction of etiocholanolone (ET) in case of postmenopausal women in compare with androsterone (AN). The ratio ET/AN confirms the above results. PMID- 1304517 TI - [A method for demonstrating chromosomes from human sperm and its application]. AB - A cytogenetic technique for analysis of human sperm chromosomes is described in this article. It is based on penetration of hamster oocytes after enzymatic treatment and inhibition of cell division during pronuclei stage. Two different methods of capacitation of sperm, that is necessary for them to penetrate the eggs have been considered. Attention is paid to manipulations and technical difficulties on consecutive steps of realization of this method. This method is applied mainly in analysis of chromosome segregation in males, that are carriers of chromosome aberrations. The possibility of using this method in other clinical cases and basic research has been presented. PMID- 1304520 TI - [A case of early detection of uterine cancer in a program of genital screening of postmenopausal patients by transvaginal ultrasonic scanning]. AB - Transvaginal ultrasound scanning was performed on 59 years old women with postmenopausal bleeding in anamnesis. Endometrial thickness was measured at its maximum in both longitudinal and transverse sections of the uterus. Also the thickness of uterus walls and ovaries in 3 planes were measured. Endometrium was irregular of 14 mm thickness. The patient had dilatation and curettage. Histology showed: adenocarcinoma I degree, and endometrial polyp. After hysterectomy the sonographic evaluation was compared with postoperative histologic measurements. Vaginal sonography is a good method of screening for uterine neoplasms in presymptomatic women. In postmenopausal patients who are not receiving hormonal replacement an endometrium of greater than 5 mm should be considered abnormal and undergo curettage and histological examination. PMID- 1304519 TI - [Congenital abnormalities of the urinary tract in Mayer-Rokitansky-Kuster-Hauser syndrome]. AB - Congenital abnormalities of the urinary tract were diagnosed in 28 per cent of authors' own cases of Mayer-Rokitansky-Kuster-Hauser syndrome. Different kinds of abnormalities were discussed and accurate diagnosis of urinary tract abnormalities before planned operation in that group of patients was emphasized. PMID- 1304521 TI - [Chronic twin to twin transfusion syndrome with non-immunologic hydrops fetalis "donor"]. AB - We describe a case of twin to twin transfusion syndrome, with few distinct features that are not commonly reported. Not immunological hydrops fetalis (NIHF) was met in donor and there was no hydramnion around the recipient. In prenatal diagnosis we additionally used the ultrasound testing of the dividing membranes and the Doppler velocimetry in umbilical arteries. PMID- 1304522 TI - [Effects of surfactant administration in neonates with respiratory distress syndrome. II. Radiographic changes]. AB - The effect of treatment of severe respiratory distress syndrome with a natural porcine surfactant (Curosurf) on the radiographic appearances and degree of aeration is described. Separate assessment of each lung of 22 preterm babies was made before and after surfactant administration. The beneficial effect of Curosurf treatment on the aeration of the lungs was seen in 19 (86%) of the babies. PMID- 1304523 TI - [Influence of risk factors in pregnancy and labor on the condition of the newborn after birth]. PMID- 1304524 TI - [Evaluation of usefulness of enzymatically determining estriol in urine and placental lactogen in serum of pregnant women with threatened preterm labor]. AB - In 40 pregnant women in the pregnancy period from 16 to 28 weeks with threatened preterm labor diagnosed after clinical investigations and recording of cardiotocogram the values of oestriol in 24-hour urine and placental lactogen in the serum was measured. These values were compared to analogous determinations in a group 40 healthy women with similar duration of pregnancy. Statistically significantly lower values of placental lactogen were found in the serum of pregnant women with threatened preterm labor. The values of oestriol in 24-hour urine were also lower, but the differences were not statistically significant. In conclusion the authors state that enzymatically determined placental lactogen in the serum is a useful method of monitoring of pregnancy with threatened preterm labor. Determination of oestriol was without any greater diagnostic significance in the case of threatened preterm labor. PMID- 1304525 TI - [Evaluation of the usefulness of enzymatic determination of estriol in urine and placental lactogen in serum of pregnant women with threatened preterm labor]. AB - The authors studied 60 pregnant women in the pregnancy period from 29-37 weeks with threatened preterm labor. The control group formed 40 healthy pregnant women in the same pregnancy period. In all pregnant women the values of oestriol in 24 hour urine and placental lactogen in the serum was measured. Statistically significantly lower values of placental lactogen were found in the serum of pregnant women with threatened preterm labor. The values of oestriol in 24-hour urine were also lower, but the differences were not statistically significant. In 40 pregnant women in the pregnancy period from 16 to 28 weeks with threatened in the serum is a useful method of monitoring of pregnancy with threatened preterm labor. Determination of oestriol was without any greater diagnostic significance in the case threatened preterm labor. PMID- 1304526 TI - [Influence of ethyl alcohol on resistance of lobular blood vessels of human placentas during in vitro perfusion]. AB - 25 human placentae lobuli obtained from normal, term deliveries were examined. Two-sided, closed perfusion according to modified Schneider method was used. Pressure of perfusion was recorded independently in maternal and fetal circulation using mercurial manometer and Ludwig kymograph++. Ethyl alcohol was dosed in single portion of 50 mg (A-1 group) and 250 mg (A-2 group) in 10% concentration (real concentration respectively 0.1 and 0.5%). In control group 0.9% NaCl was used. Decrease of the blood-vessel resistance in maternal and fetal circulation was observed. The relaxation was dependent on ethyl alcohol concentration. PMID- 1304527 TI - [Placental lactogen level and activity of oxytocinase, beta-glucuronidase and thermostable alkaline phosphatase isoenzyme in blood serum of women with ectopic pregnancy]. AB - The lack of literature data dealing with placental lactogen concentration as well as with the other biochemical parameters in blood serum in women with ectopic pregnancy was the reason we turned to that problem. In eight patients with ectopic pregnancy there was determined placental lactogen level and oxytocinase activity as well as the activity of beta-glucuronidase and thermostable alkali phosphatase isoenzyme in blood serum. The results obtained were compared to the concentration of those parameters in blood serum in women with ectopic pregnancy and to those of not pregnant women. It was stated that in women with ectopic pregnancy there was produced placental lactogen and its concentration in blood serum was lower (about 30 percent) than that in women with ectopic pregnancy. Similarly, mean value of oxytocinase activity in women with ectopic pregnancy was twice lower in comparison to that of ectopic pregnancy, while beta-glucuronidase activity was twice higher when compared to that of ectopic pregnancy values. Placental alkali phosphatase isoenzyme activity was similar in both groups of pregnant women. PMID- 1304528 TI - [Vascularization of the posterior wall of the urinary bladder in women after past cesarean section in light of microangiographic studies]. AB - Arterial vascularization of membranes in the urinary bladder wall has been studied in 14 women of reproductive age, who were bearing children. Four of them had exclusively spontaneous deliveries. Ten delivered at least once by cesarean section. The studies consisted in filling the uterine, ovarian and vesical arteries with Microtrast preparation. After the filling of vessels and fixation of the preparation in 10% formalin solution, specimens, 4-5 mm thick, were taken from the bladder wall at the junction with uterus, and comparatively specimens from the free parts of the uterus body. The serial specimens were used to obtain photographs by means of X-ray apparatus with microfocal tube, being implemented for structural studies. On the basis of the above-mentioned investigations we disclosed that the course of the blood vessels in membranes of the urinary bladder wall undergoes changes after routine dissection during the cesarean section. There is a disappearance of regular arrangement of the vascular network, particularly in mucous membrane. New vessels of larger calibre with an irregular course are seen to appear throughout the entire width. Such changes were not detected at sites distal to the field of operation. Specimens stemming from the urinary bladders of women, who delivered spontaneously, failed to reveal such changes. PMID- 1304529 TI - [Activity of superoxide dismutase (SOD) and its isoenzyme activities in newborn children and adult women and men]. AB - During fetal development, antioxidant defense mechanisms have generally been considered to be less active than those of mature newborn infants or of the adults. It has been suggested that this might reflect a lower requirement for cellular antioxidant activity because of the relatively protective intrauterine environment and the lower perfusing oxygen tension in the fetus. Inadequate antioxidant protection has been postulated as a prime factor in pathologic states such as bronchopulmonary dysplasia and retinopathy in preterm infants. To obtain a profile of changes of superoxide dismutase and it's isoenzymes (the main enzyme of antioxidant defence) in human blood during late fetal development, we studied blood samples from prematurely, on term and postmaturely born infants, and adults. Erythrocyte superoxide dismutase and Cu, Zn-SOD in plasma blood changed significantly with maturation, by term Cu, Zn-SOD activity reached a level higher than in adults. High SOD activity, perhaps, is one of biochemical specific "preparation for birth" occurs in developing fetus to help assure it's successful adaptation to comparatively O2-rich world at birth. PMID- 1304530 TI - [Influence of applicator moves to dose distribution during Selectron LDR brachytherapy]. AB - Irradiation of cancer diseases with intracavitary applicator makes impossible visual control of applicator's position during the process of irradiation. In this paper example applicator moves during the treatment are presented and their influence to dose distribution especially in reference points is discussed. Verification of applicator's position has been made by the use of roentgen films. PMID- 1304531 TI - [Role of carboplatin in treating patients with advanced ovarian cancer]. AB - Results of Carboplatin treatment of ovarian cancer were presented. Drug resistance was observed during therapy of first course type. Objective response to treatment was observed with 5 patients from 27 ones (19%). PMID- 1304532 TI - [Prognostic factors in breast cancer]. AB - This treatise dealt with a particular prognosis factors analysis carried out on a large group of breast cancer patients. Creating analysis is the main task to establish both the way of adjuvant treatment and the treatment results foresight. PMID- 1304533 TI - [Surgery of brain angioma (hemangioblastoma cerebelli) during the 31st week of pregnancy]. AB - The course of treatment of 28-years old pregnant woman by reason of the tumour of the left cerebellum hemisphere was presented. The urgent operation was performed in 31-st week of pregnancy because of increase of intracranial pressure. The tumour 5 cm in diameter was removed totally. Pathomorphological examination demonstrated haemangioblastoma. Cesarean section was performed in 38-th week of pregnancy by reason of cerebrospinal fluid accumulation in tumor place. Nine month after operation and 7 month after delivery mother and child are in good condition. PMID- 1304534 TI - [Coexistence of sertolioma with borderline (adenoma-cystoma-fibroma) tumor in the ovaries of a 69 year old patient]. AB - A rare case of coexistence of gonadal neoplasm Sertolioma with boundary line tumor with epithelial fill in ovaries in 69 old patient was described. Current diagnostic and prognostic possibilities in such cases were discussed. PMID- 1304535 TI - [Marking and detection of DNA of leptospires in the dot-blot and situ hybridization with digoxigenin-labelled probes]. AB - DNA of Leptospira interrogans sv. lai strain 017 was labelled with digoxigenin or alpha 32P or biotin and used as probes to detect DNA of leptospires. Probes labelled with digoxigenin were able to detect 0.1-1 pg of homologous DNA and 10(2) of L. interrogans sv. lai strain 017. Probes alpha 32P and biotin detected 1 pg and 10 pg of homologous DNA and 10(3), 5 x 10(3) of L. interrogans sv. lai strain 017 respectively. These three probes couldn't detect L. biflexa sv. patoc strain Patoc I, L. illini strain 3055, Escherichia coli. Bacillus aerogenes capsulalus, Salmonella anatis, K-DNA of Leishmania, and of human WBC. Comparison of digoxigenin-, alpha 32P- and Biotin-labelled probes in the dot-blot hybridization assay on different serogroup sv. of leptospires revealed that digoxigenin-labelled probes were more sensitive than alpha 32P and biotin labelled probes. The results indicate that digoxigenin-labelled probes DNA can be used for detection of leptospires in field and clinic. We also report procedures in situ hybridization with leptospira in tissues smear and plasma sediment of an experimentally infected guinea pig. It offers the advantage of recognizable of leptospiral morphology in combination with a hybridization signals. The results indicate that digoxigenin-labelled DNA probes of 017 strain might provide tool for routine diagnosis and classification in cases of leptospiral interrogans infection. PMID- 1304536 TI - [The effect of 211At labelled monoclonal antibody against gastric cancer on DNA, RNA and protein synthesis in gastric cancer cell]. AB - By means of nuclide precursor incorporation, the effects of 211At labelled monoclonal antibody against gastric cancer (211At-3H11McAb) on DNA, RNA and protein synthesis in gastric cancer cell were studied. The results show that 211At-3H11McAb and Na211At-3 inhibit 3H-TdR, 3H-UR and 3H-Leu incorporation, especially 3H-UR incorporation, into gastric cancer cell at 3.7 x 10(4)Bq and 1.85 x 10(5)Bq; the inhibiting rates depend on concentration. The DNA biosynthesis in gastric cancer cell gradually recover after the drug is removed, suggesting that the drug should exert an inhibiting action on DNA biosynthesis in tumor cell through interference of DNA metabolism. PMID- 1304537 TI - [Biochemical and immunological characterization of desmosomal proteins]. AB - Desmosmoes were dissolved by incubation at 100 degrees C for 30 minutes in lysis buffer containing 9.5 M urea. SDS-PAGE revealed seven high molecular weight (> 67 kd) bands and some keratins. Seven of these were considered to be major bands. Bands 1 and 2 with M(r) values of 250 kd and 215 kd, called desmoplakins I and II. Polypeptide bands 3, 4a 4b, 5 and 6 had M(r) values of 165kd, 130kd, 115kd, 83kd and 75kd, respectively. 2-2.5mg of Desmoplakin I was obtained by a preparative electrophoresis; the purity reached 93.1%. The isoelectric pH range was between 6.8 and 7.2, and the amino acid compositions displayed a relatively high content of glycine. It was found that McAb Desmoplakin I recognized specifically the 250kd antigenic band by immunoblotting. PMID- 1304538 TI - [Detection of anti-idiotypic antibody specific for anti-HBs in HBsAg positive serum]. AB - An ELISA for detecting anti-idiotypic antibody specific for anti-HBs(anti-anti HBs, Ab 2) was devised and used to detect twenty-three asymptomatic HBsAg positive sera. Of these HBsAg positive samples, five were positive for anti-anti HBs. Three anti-anti-HBs positive samples and two anti-anti-HBs negative samples were checked by immune electron microscopy (IEM). Non HBV particles were found in the anti-anti-HBs positive samples, but the particles were seen in one of the anti-anti-HBs negative samples. According to the immune networks theory, the anti anti-HBs with the characteristic of HBsAg internal can mimic HBsAg and bind to anti-HBs(Ab 1), so that the anti-anti-HBs may interfere the routine detection of HBsAg and results in false positive. The data described above demonstrated the existence of this consideration. The authors suggested that samples with HBsAg positive, especially those from asymptomatic carriers should be detected for anti anti-HBs in order to rule out the interference of anti-anti-HBs. PMID- 1304539 TI - [Studies on human chorionic gonadotropin (HCG)-binding protein from Pseudomonas maltophilia by ligand blotting assay]. AB - A ligand blotting technique was developed to study the HCG-binding protein from Pseudomonas maltophilia after size separation by SDS-polyacrylamide gel electrophoresis under nonreducing conditions. The separated proteins were transferred to a nitrocellulose sheet, which was subsequently incubated with [125I]iodo HCG, and subjected to determination for radioactivity in gamma counter. A radioactivity peak equivalent to an M(r) 70000 appeared, which was not observed when the hormone incubation was performed in the presence of an excess of unlabeled HCG. The peak also disappeared when the protein samples were treated with reducing agent, which showed that integrity disulfide bonds of the protein was essential for the protein-hormone interaction. In addition, position of the radioactivity peak which was due to the binding of [125I]iodo HCG to western blots of the HCG-binding protein was corresponding to that of the antibodies against the HCG-binding protein recognizing a 70000 protein on the western blots. These results show that the HCG-binding protein from Pseudomonas maltophilia is an M(r) 70000 protein and that the HCG-binding protein contains at least one disulfide bond essential to its binding activity. PMID- 1304540 TI - [Study on casting precision of plat castable ceramic crowns]. AB - The plat castable ceramic crown was made with investment material prepared in our college with our own casting technique by a Chinese-made casting machine. The accuracy and fitness of the crown were studied and appraised. Results show that the margin of fitness is 46 microns and that the cement film thickness of the dies in the spacer material group is 65.13 microns. Hence the results are satisfactory. The Plat castable ceramic crown might be used in clinical dentistry. PMID- 1304541 TI - [Histological study of the structure of artificial plaque]. AB - Five cariogenic bacteria were used to produce a plaque, called artificial plaque, by sequential culture in vitro. The results showed that the artificial plaque is very similar to the natural one in morphology and structure. Artificial plaque may be taken as an excellent model in vitro for the studies on cariogenicity of dental plaque. PMID- 1304542 TI - [Study of the mechanistic model for substrate-enzyme interaction on rabbit thymus tissue-based biosensor]. AB - The authors studied the possible mechanistic model for substrate-enzyme interaction on rabbit thymus tissue-based biosensor by tissue chemistry and potentiometric method. The results show that cell construction of coarsely ground and immobilized fresh rabbit thymus is mostly intact. The channels of lipid double-molecule in the cell membranes were expanded. This tissue sensing membrane is better than the natural tissue membrane in terms of electrode response. The membrane has been found to be usable for up to 25 days with a response time of 8 minutes and slope of 51.2mV/decade. The authors suggested a new idea of "frame" construction. PMID- 1304543 TI - [A computerized analysis of phrenic nerve discharge signal]. AB - The authors offered a method of computerized analysis to solve the problems met in the manual measurement of the signal of phrenic nerve discharge (PND). An envelope was gained via digital fullwave rectification and filter from the acquired PND signal. From it, some important parameters were measured automatically. The program ran well in animal experiments. The values of the PND parameters obtained by computer showed no significant difference as compared with the averaged values measured manually by researchers. PMID- 1304544 TI - [Observation of paired-pulse depression in CA1 region of hippocampal slices from coriaria lactone-kindled rats]. AB - Paired-pulse depression (PPD) technique was used to investigate the potency of recurrent synaptic inhibition mediated by GABA in area CA1 of 54 hippocampal slices from coriaria lactone (CL)-kindled and control rats. When paired stimuli were sent to the axon of CA1 pyramidal cell and Schaffer collaterals, the effect of population spike PPD lasted about 40-60ms; no significant change was observed on PPD potency between kindled and control groups (P = 0.06, 2-way ANOVA). The results indicate that the GABA-ergic synaptic inhibition seemed not to play a key role in the maintenance of the chemical kindling induced by CL. PMID- 1304545 TI - [Bacterial microcolony and its primary applications]. AB - A new rapid and useful microcolony technique was developed by using cellulose acetate membrane as a supporter. The bacteria were inoculated on the membrane and cultivated for 3-6h. Then the membrane was rendered, fixed and colored. The microcolonies were observed and counted under the microscope. By using this technique the microcolonies of 139 strains of bacteria were observed. 72 strains of Staphylococcus were differentiated by means of observing the characteristics of the microcolonies. The correlation rate between the microcolony method and the routine method was 90.28%. This technique was also first used to determine the bacteria numbers in urine within 6h, and the advantages of it were significant compared with the plate count method. PMID- 1304546 TI - [Effects of mixture of Astragalus membranaceus, Fructus Ligustri lucidi and Eclipta prostrata on immune function in mice]. AB - A Chinese medicine mixture containing Astragalus membranaceus, Fructus Ligustri Lucidi and Eclipta prostrata(AFE), was fed to mice 9g/kg, 20g/kg, respectively for seven days. Observe the effects of AFE on the immune function in mice. The experiment showed that the two dosages of AFE could obviously raise the conversion percentage of lymphocytes (P < 0.01) and serum IgG level (41%-47%) of the mice. The weights of the thymus and spleensed increased in the two groups compared with those in the normal control. The larger dosage of AFE could also raise activity of Adenosine Deaminase (ADA) obviously (P < 0.01). AFE turned out a resistance to the immunosuppressive effect caused by cyclophosphamide. PMID- 1304547 TI - [Partial purification and analysis of allergenicity, immunogenicity of Ginkgo biloba L. pollen]. AB - Pollens of Ginkgo biloba L. (G.b.l.p) have been found to be a kind of important allergen which causes pollinosis in Chengdu. The goal of this study is to purify G.b.l.p and to determine the allergenicity and immunogenicity of various fractions. Crude extract was purified by gel filtration with Sephadex G25, then G75. Two elution peaks were observed. On SDS-PAGE, the molecular weights of protein of the 1st peak and the valley were 30-42 kd and 13-18kd, respectively, and that of the 2nd peak was less than 13 kd. 40 patients with allergic rhinitis and/or asthma underwent the skin test with crude extract and various fractions of gel filtration; it revealed that the strongest allergenic activity existed in the 1st peak and there was mild allergenic activity in the 2nd peak. The in vitro allergenic activity and immunogenic activity of various fractions were examined by ELISA inhibition test. It was further confirmed that the allergenic activity and immunogenic activity of the 1st peak were the strongest, and those of the 2nd peak were the lowest. It is suggested that diagnosing reagents can be made satisfactorily by partial purification, i.e. discarding the inactive fractions, since allergenicity exists in various fragments. But fractions of allergen with high IgG immunogenicity should be selected to produce immunotherapy agents so as to enhance the production of blocking antibody and thus improve the therapeutic effect. PMID- 1304548 TI - [Preventive effect of green tea on MNNG-induced lung cancers and precancerous lesions in LACA mice]. AB - Three hundred and ninety LACA mice of seven weeks old were used in 2 batches (96.4 wks and 106 wks) for studying the preventive effect of green tea on MNNG induced lung cancers and precancerous lesions. These mice (within each batch) were randomly allocated to four groups, namely, positive control (MNNG), green tea (GT), complex (MNNG + GT), and blank control (C) group. In MNNG group, MNNG 250 micrograms) was injected intravenously every five days for seven times in each mouse; the total dosage of MNNG was 1.75mg. In GT group, according to W/W, 5% GT dust was well mixed into 95% common diet for long-term breeding. In complex group, MNNG was given as that in MNNG group and the mice were reared as those in GT group. The mice in MNNG group and in C group were all reared by common diet. The mean amount of daily intake of feed was 10g. The number of effective animals was 354. The results of experiments showed different degrees of preventive effect of green tea on MNNG-induced lung cancers and precancerous lesions in LACA mice. Green tea exerted an effect on the number of induced cancers and precancerous lesions, causing a drop of the cancerous rate from 79.75% to 13.59% and the number of lung tumor down to 1/7-1/16 that of the MNNG group, i.e. down to less than one tumor nodule per mouse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304549 TI - [Physiological changes in middle-aged persons and old people before and after tennis competition]. AB - An examination of medical and physiological changes before and after tennis competition was performed on 71 middle-aged persons and old people in order to know whether they were adapted to this intense match or not. The result was that in the male group 1 (50-59 yrs), the heart rate, respiration rate and blood pressure before and after the tennis game had no significant differences (P > 0.05), indicating that this group was fit for the tennis competition, in the male group 2 (60-69 yrs) and male group 3 (70-79 yrs), as age advances, the number of unfitness to this game was increased gradually; in the female group (50-59 yrs), 28.5% of them showed a marked increase in the heart rate after the competition. We think that when persons have an electrocardiogram showing a significant undue changes of the ST segment and T wave after the contest, they are not suitable to this violent competition. So the medical surveillance is very important for the old people to play violent games such as tennis. The periodical health examination should be done before any exercise event with emphasis on the cardiovascular system so that the old sportsman can choose the proper exercise item and take self-control during the exercise. PMID- 1304550 TI - [Survey of suicidal mortality rate in several districts of Sichuan province]. AB - A survey of the suicidal mortality rates in two cities and six districts in Sichuan province was carried out from 1980 to 1988 by the authors. The average suicidal mortality rate (ASMR) in these districts from 1980 to 1988 was 15.5/10(5), and the population and suicidal mortality rate positively correlated, r = 0.53. The ASMR in the male was 14.9/10(5), in the female 17.1/10(5), in the urban area 9.4/10(5), in the rural area 21/10(5), and the ASMR in the urban area was higher than that in the rural area (P < 0.05). The peak age of suicidal mortality was around twenty years. PMID- 1304551 TI - Parkinsonian-like tremor induced by a combined application of chlorpromazine and pentobarbitone in cats with left-paw preference. AB - A Parkinsonian-like tremor can be induced by a combined application of chlorpromazine and pentobarbitone in cats. Interestingly enough, only cats with left-paw preference were found to have a predisposition to this drug-induced tremor. The cats with ambidexterity and right-preference in paw use did not show any visible tremorogenic action of these drugs. Especially the proximal muscles of all four extremities showed oscillations with a frequency of about 12 per second in all animals tested, which completely disappeared after i.v. application of lioresal, atropine and biperiden. It was suggested that this new drug-induced tremor model may reflect an impairment within the cortico-striato-pallido-thalamo cortical feedback loop. It was also concluded that left-handers may have an increased predisposition to centrally acting drugs than nonleft-handers. PMID- 1304552 TI - Handedness, dyslexia and twinning in homosexual men. AB - A study of handedness, dyslexia, stuttering and twinning, was included in a study of sexual habits of homosexual men. A questionnaire was mailed to homosexuals, and 394 forms suitable for data analysis were received. The results showed an increased rate of lefthand writing (17.5% compared to 8-8.4%), and a clear left shift. There were increased occurrence of both stuttering (7.1% compared to 1.6%) and reading difficulties (7.9% compared to 1-3%). The incidence of twins was lower than the population (1.3%). The results confirm earlier attempts to show a left shift in homosexuals, and support Geschwind's hypotheses about etiological factors for both lefthandedness and homosexuality. PMID- 1304553 TI - Role of cerebral hemispheres and regions in processing hemifacial expression of emotion: evidence from brain-damage. AB - Patients with focal brain-damage, right or left hemisphere-damage (RHD/LHD) and anterior or posterior region-damage (ARD/PRD), and normal controls (NC) were asked to match the photographs of (left-right) hemifacial expressions of emotions, positive (happy-surprise), negative-aroused (fear-anger), negative nonaroused (sad-disgust). Findings indicated that (a) NC subjects were significantly superior to brain-damaged patients; the difference between RHD and LHD patients was nonsignificant, and (b) ARD patients were significantly inferior to PRD patients who, in turn, were significantly inferior to NC subjects, in the perceptual matching task with hemifacial affective stimuli. PMID- 1304554 TI - The pineal gland and the menstrual cycle. AB - The menstrual cycle reflects the expression of a cyclical process involving the interaction between the hypothalamic-pituitary axis and the ovaries. This complex process requires an integrated neural and humoral control mechanism. It is now well established that a hypothalamic "transducer" located in the medial basal hypothalamus integrates neural and humoral information and translates it into an oscillatory signal which eventually results in the release of the gonadotropin releasing hormone (GnRH), triggering the secretion of gonadotropins from the pituitary gland. Recent animal studies indicate that melatonin influences the functions of the hypothalamic-pituitary-gonadal axis by modifying the firing frequency of the hypothalamic GnRH pulse generator. Consequently, the pineal gland, through the action of melatonin, may exert an important modulatory effect on the mechanisms controlling menstrual cyclicity. Furthermore, abnormal melatonin functions may be involved in the pathogenesis of several disorders of the menstrual cycle including some forms of hypothalamic amenorrhea such as exercise and malnutrition-induced amenorrhea. Consideration of pineal melatonin functions provides a new dimension into the understanding of the neuroendocrine mechanisms governing the cyclical phenomena of the female reproductive system. PMID- 1304555 TI - The pineal gland and multiple sclerosis. PMID- 1304556 TI - The relation of body height to handedness in male and female right- and left handed human subjects. AB - The association between body size and the degree of hand preference was studied in male and female right- and left-handed human subjects. Hand preference was assessed by the Edinburgh Handedness Inventory. In left-handers (total sample), there was a significant, negative linear correlation between the degree of left hand preference and body height. There was no significant correlation between these parameters if the males and females were considered separately. In right handers (total sample), body height was found to be significantly and negatively linearly correlated with the degree of right-hand preference. A similar correlation was observed in males without familial sinistrality (FS-) and in FS+ females. There was no significant correlation between these parameters in FS+ right-handed males and FS- right-handed females. It was suggested that hormones affecting body height and brain size such as human growth hormone and testosterone would also contribute to the development of cerebral lateralization. PMID- 1304557 TI - Alpha rhythm and the pineal gland. AB - Alpha rhythm is classically described as a bilateral posterior rhythm of substantially constant frequency in the range of 8-13 Hz which is enhanced by mental relaxation and blocked by attention. Since the full expression of alpha rhythm has been shown to occur coincident with puberty, it is possible that the establishment of alpha rhythm is subject to neuroendocrine influences which govern psychosexual maturation. There is ample evidence to indicate that the pineal gland is implicated in cerebral maturation and psychosexual development. Nocturnal plasma melatonin levels have been shown to decline progressively throughout childhood reaching a nadir at puberty. Since administration of melatonin has been reported to block alpha rhythm, it is proposed that the progressive decline in melatonin secretion during childhood facilitates the maturation of the alpha rhythm. Consequently, the presence of alpha rhythm could be used as a neurophysiological marker for the activity of the pineal gland and disorders associated with absent or delayed maturation of the alpha rhythm such as autism, dyslexia, personality disorders, epilepsy, Tourette's syndrome, and schizophrenia might be related to disturbances of pineal melatonin functions in early life. Moreover, since the EEG patterns associated with cerebral immaturity (i.e., slowing, absence of alpha activity) are more pronounced in the left hemisphere, this hypothesis implies differential influence of the pineal gland on hemispheric maturation potentially accounting for the vulnerability of the left hemisphere to cerebral insults. PMID- 1304558 TI - Auditory event-related potentials among dyslexic and normal-reading children: 3CLT and midline comparisons. AB - Event-related potentials (ERP's) to verbal and non-verbal auditory stimuli were recorded from normal-reading and from dyslexic children while performing a target detection task ("oddball" paradigm). Two methods of analysis were used: (1) Peak latency and amplitude measures of P3 recorded from 3 midline electrodes; (2) P3 apex latency, amplitude and orientation in the three-channel Lissajous' trajectory (3CLT) derived from 3 orthogonal pairs of electrodes. P3 peak amplitude was significantly attenuated in dyslexic children compared to normal reading children and in response to verbal stimuli compared to non-verbal stimuli. P3 apex latencies were longer and apex amplitudes larger in response to non-verbal compared to verbal stimuli. The most striking finding involved P3 apex orientation, which pointed in an upward-posterior direction with a slight tilt to the left among normal readers, but with a tilt to the right in dyslexics. PMID- 1304559 TI - Magnetic fields alter the circadian periodicity of seizures. AB - We have recently reported that application of external, weak magnetic fields attenuated seizures in epileptic patients (Anninos et al., 1991). However, the mechanisms by which magnetic stimulation reduces seizure activity are unknown. We present four non-selected epileptic patients the first to be rated by the senior author, in whom treatment with magnetic fields attenuated the severity of seizures and also altered the circadian occurrence of seizures. The first patient, a 27-year old woman, had generalized tonic-clonic seizures which occurred almost exclusively at night. Following treatment with magnetic fields she experienced attenuation of seizures which then occurred only after waking up in the morning. The second patient, a 42-year old man, had generalized tonic clonic seizures which occurred randomly during the day and night. Treatment with magnetic fields resulted in disappearance of nocturnal seizures with seizures now occurring exclusively during the day. The third patient, a 21-year old woman had generalized tonic-clonic seizures which occurred randomly during the day. After treatment with magnetic fields she was free of seizures for 7 months, but recently experienced one attack in the morning hours while sleeping. The fourth patient, a 39-year old woman had secondary generalized seizures since the age of 12. Prior to treatment with magnetic fields she had 8-10 seizures daily which occurred randomly during the day and night hours. Magnetic treatment resulted in attenuation in seizure frequency (1-2/day) with seizures now occurring only during the day. We propose, therefore, that since the pineal gland is a magnetosensitive organ which "transduces" environmental information of the light dark cycle and of the earth's magnetic field into an endocrine message mediated via the circadian release of melatonin, and since it is recognized that melatonin attenuates seizure activity, artificial magnetic fields attenuate seizure activity by altering the functions of the pineal gland. PMID- 1304560 TI - Voluntary immunomodulation: a preliminary study. AB - This study explored the effects of relaxation and imagery procedures on the voluntary self-regulation of immune responses. Immune studies of 19 adults were made before and after a 45 minute intervention consisting of relaxation with imagery aimed at enhancing immune activity. A self-report measure of psychological distress was completed before each blood sample. Results indicate that the seven blood measures of immune functioning were measured with adequate reliability and consisted of two sets of immune parameters. A statistically significant increase in one of the mitogen measures and a marginally significant increase in one of the blood count measures was found following the relaxation/imagery procedure. Age, hypnotizability, and their interaction significantly predicted change on the set of blood count measures but not on the set of mitogen measures. As expected, level of subjective psychological distress generally decreased following the intervention. The methodological limitations of this study included limited sample size and absence of a control group. PMID- 1304561 TI - Voluntary modulation of neutrophil adhesiveness using a cyberphysiologic strategy. AB - In a study of voluntary immunomodulation, 45 subjects were assigned either to a control group or one of two experimental groups. All groups had blood and saliva samples collected before and after either a 30 minute rest condition (Control group) or a 30 minute cyberphysiologic strategy (Experimental groups) to increase neutrophil adherence. These samples were analyzed on a range of immunologic measurements including neutrophil adherence. The second experimental group practiced a cyberphysiologic strategy two weeks prior to the experimental session. Subjects in each group returned to repeat their exercise in a second session the following week. Analysis of all immune measurements revealed statistical significance for changes in neutrophil adherence. These studies suggest that such strategies may be used to effect changes in immune cell functions. Analysis further revealed that those subjects with prior cyberphysiologic training were able, by the second session, to induce a significant increase in neutrophil adherence. PMID- 1304562 TI - Weak magnetic fields as a novel therapeutic modality in Parkinson's disease. PMID- 1304563 TI - Potentials associated with the initiation and inhibition of visually triggered finger movement in humans: the "no-go potential" in the go/no-go paradigm. AB - Surface event-related potentials associated with visually triggered movements (Go) and the inhibition of planned movements (No-Go) of the right index finger were examined in seven normal healthy subjects. Subjects' response priming was manipulated by presenting two sessions which either emphasized the Go condition (50 go trials vs. 30 no-go trials) or the No-Go condition (30 go trials vs. 50 no go trials). Stimulus-locked waveforms showed enhanced components (P1-N1, N2, N1 P300) for the No-Go trials particularly in the response priming which emphasized the Go condition. It is suggested that the inhibition of planned movements is associated with surface negativity which trails the sensory P1-N1 potential yet may partially overlap it and therefore influence its amplitude. This "no-go" potential is dependent on the response priming of the subject and is most apparent when fast responses are planned and then arrested. PMID- 1304564 TI - The brain in fractal time: 1/f-like power spectrum scaling of the human electroencephalogram. AB - "1/f-like" power spectrum scaling is a ubiquitous feature of complex systems. In such scaling, the power spectrum of a given time series is dominated by an inverse power law, resulting in an inverse linear relation between log power and log frequency. The 1/f-like power spectrum scaling properties of human, resting eyes-closed and eyes-open EEG were examined. For both eyes-closed and eyes-open EEG, log power had a significant inverse linear relation with log frequency. The slope of this relation was not correlated with previously-calculated Grassberger Procaccia dimension estimates for the same data, indicating that the EEG is not a 1/f-like stochastic process. Further, the degree of deviation from perfect log power versus log frequency linearity was related to power in the 8-12 Hz alpha frequency band. It is speculated that this deviation may be related to the low dimension of a chaotic alpha rhythm relative to other EEG rhythms. PMID- 1304565 TI - Pattern reversal visual evoked potentials (PVEPs) in transient ischemic attacks (TIAs) and prolonged reversible ischemic neurological deficits (PRINDs) of anterior circulation with normal EEGs and normal cranial CTs. AB - Out of 75 patients with TIA or PRIND we selected 9 TIAs and 6 PRINDs with normal EEGs and CCTs, full recovery of neurological function, no history of amaurosis fugax and no findings of visual impairments. PVEPs were derived from 01-02 to Fz and Cz as ground following binocular pattern reversal visual stimuli of 1.9 Hz. Interhemispheric differences of the latencies of P60, N80, P100 and of the amplitudes N80/P100 and P100/N140 were compared with the corresponding parameters of 22 age matched controls. In contrary to the latency differences the interhemispheric difference of the amplitude N80/P100 was highly significantly larger (33.5 +/- 16.0%) in patients than in the control group (12.8 +/- 9.8%) (p < or = .0005). The amplitude P100/N140 behaved the same way (p < or = .025); the amplitude of the affected side being smaller. There were no statistical differences between TIAs and PRINDs and a tendency was seen for normalization of the differences with increasing time distances between the onset of the ischemic attack and the point of time of the recordings. PMID- 1304566 TI - Relationship of serum zinc levels to hand preference, skull length and serum gonadal hormone levels in right-handed young adults. AB - The association between serum zinc (Zn) level and the degree of hand preference was studied in right-handed young adults. Hand preference was scored by the Waterloo Handedness Questionnaire. Serum Zn level was determined by the flow injection analysis-atomic absorption technique. Zinc was found to be positively linearly and significantly correlated with the degree of right hand preference in the sample of males with familial sinistrality (FS+) and FS- females with right eye and right foot preference. There was a negative linear correlation between these variables in FS+ females. Skull length showed a significant negative linear correlation with zinc in FS+ males and females, but a positive linear correlation in FS- females. In FS- females, there was a significant positive linear correlation between serum gonadal hormone binding globulin (GBG) and serum Zn levels. In FS+ males, there was a significant negative linear correlation between serum GBG and Zn levels, and a significant positive linear correlation between serum free testosterone level and serum Zn level. It was suggested that zinc may influence the degree of the right hand preference by hormonal mechanisms according to genetically established brain organization. PMID- 1304567 TI - Testosterone and estradiol in right-handed men but only estradiol in right-handed women is inversely correlated with the degree of right-hand preference. AB - Relations of sex hormones to the degree of right-hand preference was studied in right-handed male and female adult subjects. Hand preference was assessed by the Edinburgh and Waterloo Handedness Questionnaires. Males consisted of weakly, moderately, and strongly right-handed subjects. Females comprised only moderately and strongly right-handed subjects. In females, only serum estradiol was found to be negatively linearly and significantly correlated with the degree of right-hand preference. In males, testosterone, as well as estradiol, showed a significant negative linear correlation with the degree of right-hand preference. Sex hormone binding globulin also showed a similar relation to hand preference in males. Thus, nearly all sex hormones caused a decrease in the degree of right-hand preference in males, whereas only estradiol had the same effect on hand preference in females. This would be the cause of stronger right-hand preference in females than males and vice versa. PMID- 1304568 TI - Luria's approach to neuropsychological assessment. AB - A. R. Luria's approach to neuropsychological assessment was examined. Three basic points of departure from Luria are presented: his interpretation of cognitive activity as functional systems, his emphasis on the individualized approach, and the importance of the analysis of the errors. A distinction was introduced between Luria's neuropsychological testing, and Luria's neuropsychological approach; the former refers to the specific set of neuropsychological tests Luria used and developed and the latter, to the specific clinical use of these tests. It is emphasized that Luria's basic contribution to assessment in neuropsychology, refers to the clinical approach he proposed and developed. Problems related to the normalization and validity of neuropsychological tests are analyzed. It is concluded that different approaches in neuropsychological assessment are related to the specific goals for which neuropsychological assessment is performed. PMID- 1304569 TI - Visual evoked potentials, attention and mnemonic abilities in children. AB - We analyzed the correlation between attention and mnemonic processes and different visual evoked potential (VEP) parameters. A group of 34 children between 9 and 13 years old was studied. VEPs were recorded in C3, C4, P3, P4, O1, O2, T5 and T6 with linked ear lobes as reference. Two different types of stimuli were used: flash and checkerboard pattern. The power of VEPs was calculated as the sum of the square amplitude values for different time epochs. Correlation coefficients between left and right homologous VEPs were also computed. A visual selective attention task divided into 5 items of increasing difficulty and the Sternberg paradigm were applied. The performance was automatically evaluated by the computer, giving the number of correct responses (NCR) and other measures of performance. Correlation coefficients between VEP parameters and the scores obtained in the performance of tasks were calculated. It was observed that power in P3, P4, T5, and T6 and the correlation coefficients between central, parietal and temporal VEPs were positively correlated with NCR of both tasks. However, power in O1 and O2 was negatively correlated with NCR. PMID- 1304570 TI - Lateralization of the epileptogenic focus by computerized EEG study and neuropsychological evaluation. AB - The localization of the epileptogenic focus relies on different factors. In patients with partial seizures, asymmetries in EEG background activity were measured by a statistical evaluation of spectral data. Neurophysiological results were compared with neuropsychological findings and MRI. Fifteen of 22 patients showed asymmetries in EEG background activity. The most prominent abnormality was a statistically significant increase of slow activity observed in 59% of cases. Delta asymmetry coincided with the site of lesions, evidenced by MRI, in 83% of patients; with the site of decreased beta activity in 60% and with the maximum level of spiking activity in 58% of cases. Neuropsychological tests showed a lateralization of the hemispheric function which coincided with delta asymmetry in 33% of patients. These results suggest that the EEG background activity, when compared with other parameters, may represent a useful method in lateralizing the epileptogenic focus. PMID- 1304571 TI - Amine accumulation: a possible precursor of Lewy body formation in Parkinson's disease. AB - It is now well recognized that the hypothalamus is an important site of neuropathology in Parkinson's disease (PD). Lewy bodies, a marker of nerve cell degeneration and a pathological hallmark of PD, have been observed frequently in the hypothalamus of PD patients by Lewy (1923) and other investigators and confirmed by more recent systematic studies by Langston & Forno (1978). Both Lewy and Langston & Forno found a predilection of Lewy body formation in specific hypothalamic nuclei with the tuberomammillary, lateral, and posterior areas containing by far the highest average counts per nucleus. Selective vulnerability of the tuberomammillary, lateral, and posterior hypothalamic cell groups to degeneration has been observed also in aging, postencephalitic Parkinsonism, Alzheimer's disease, and schizophrenia. The susceptibility of these particular nuclei to degenerative changes including Lewy body formation is not presently understood nor are the mechanisms by which Lewy bodies are formed in PD and other CNS disorders. Accumulation of amines, a pathological process which follows degeneration of catecholamine-containing neurons in experimental animals, also occurs most frequently in the lateral and posterior hypothalamic areas. In the present communication we propose that in PD, amine accumulation may be a precursor to Lewy body formation and that the susceptibility of certain hypothalamic areas to Lewy body formation may be related to their propensity to accumulate amines. Furthermore, the frequent co-existence of Lewy bodies and Alzheimer's neurofibrillary tangles in the lateral and posterior hypothalamic nuclei suggest that they may share a common pathogenetic etiology. If confirmed, this hypothesis may provide an experimental model by which the formation of Lewy bodies and neurofibrillary tangles may be investigated. PMID- 1304572 TI - Attenuation of epilepsy with application of external magnetic fields: a case report. AB - We have previously demonstrated that magnetoencephalographic (MEG) brain measurements in patients with seizure disorders show significant MEG activity often in the absence of conventional EEG abnormalities. We localized foci of seizure activity using the mapping technique characterized by the ISO-Spectral Amplitude (ISO-SA) on the scalp distribution of specified spectral components or frequency bands of the emitted MEG Fourier power spectrum. In addition, using an electronic device, we utilized the above recorded activity to emit back the same intensity and frequency of magnetic field to the presumed epileptic foci. Using this method we were able, over the past two and one-half years, successfully to attenuate seizure activity in a cohort of over 150 patients with various forms of epilepsy. We present a patient with severe epilepsy and behavioral disturbances in whom application of an external artificial magnetic field of low intensity produced a substantial attenuation of seizure frequency which coincided with an improvement in the patient's behavior. This case demonstrates that artificial magnetic treatment may be a valuable adjunctive procedure in the management of epilepsy. PMID- 1304573 TI - Differential effects of left versus right seizure focus on human hippocampal evoked responses. AB - Hippocampal evoked potentials were recorded using the P3 tonal oddball paradigm in 30 patients with unilateral temporal lobe seizure focus. Spectral power of the evoked potentials was decreased on the side of seizure focus, but this reduction was much greater when the focus was on the left. The effect of left/right focus does not appear to be due to group differences in age, sex, seizure duration, or operative pathology. Remote or finer left/right structural differences or differential left/right hippocampal processing for the sequential tonal task are possible explanations. PMID- 1304574 TI - Amyloid precursor protein might be a receptor for basic fibroblast growth factor. PMID- 1304575 TI - Weak magnetic fields in the treatment of Parkinson's disease with the "on-off" phenomenon. AB - Application of external weak magnetic fields recently has been reported to be efficacious in the treatment of a 62-year-old patient with idiopathic Parkinson's disease (PD) complicated by levodopa-induced fluctuations in motor response ("on off"). I report an additional case of a 67-year-old man with idiopathic PD and levodopa-related motor fluctuations who likewise experienced marked and sustained improvement in Parkinsonian symptoms and amelioration of "on-off" symptoms following the application of external weak magnetic fields. Based on these observations it is concluded that artificial weak magnetic fields may be beneficial for the treatment of PD complicated by levodopa-related "on-off" phenomenon. Furthermore, since in experimental animals external magnetic fields alter the secretion of melatonin, which in turn has been shown to regulate striatal and mesolimbic dopamine-mediated behaviors, it is proposed that the antiParkinsonian effects of weak magnetic fields are mediated via the pineal gland. PMID- 1304576 TI - The development of the perichondrium in the avian ulna. AB - The development of the perichondrium surrounding the ulna of chick embryos was examined between stages 26 and 34 (Hamburger & Hamilton, 1952), i.e. 5.5-8 d of incubation. The first appearance of a barrier between cartilage and adjacent tissue was observed at stage 27 when cells were arranged circumferentially around the central flattened core, but no true perichondrium was seen until chondrocyte hypertrophy began at stage 30. At this stage, cells in the barrier became elongated parallel to the long axis of the rudiment and overlapped. With further cell hypertrophy, the perichondrium consolidated and by stage 31 a distinct, compact structure, several cells thick and exhibiting cell-cell contacts had formed around the hypertrophic cell region. By stage 32, overlapping perichondrial cells could be seen surrounding the flattened cell region and this structure consolidated as cell hypertrophy spread from the centre towards the ends of the rudiment. The rounded cell zone at the epiphyses never formed a distinct perichondrium during the time course of this study. This differential structure of a compact perichondrium surrounding the hypertrophic cell region, a loose perichondrium surrounding the rounded cell region and an intermediate perichondrium surrounding the flattened cell region may facilitate the morphogenesis of the rudiment by acting as a constraining sheath restricting radial expansion but favouring longitudinal expansion. PMID- 1304577 TI - Immunomodulation of low dose streptozocin diabetes in mice reveals that insulitis is not obligatory for B cell destruction. AB - Twenty male C57Bl/J mice were injected with 50 microliters complete Freund's adjuvant (CFA) 1 wk before and 1 wk after induction of diabetes with 45 mg streptozocin (STZ)/kg body weight i.p. over 5 d. CFA administration prevented islet infiltration. Inflammatory cells were not seen within any of the islets observed. However, islet B cell destruction still occurred. These cells showed evidence of considerable damage, containing swollen mitochondria, contracted nuclei and areas of vacuolation and degranulation. Inflammation is therefore not obligatory for the development of low dose STZ induced diabetes. PMID- 1304578 TI - An electron microscopic and morphometric study on the GABA-immunoreactive terminals in the cuneate nucleus of the rat. AB - Immunogold labelling was used to identify GABA-immunoreactive (GABA-IR) terminals in the cuneate nucleus of the rat. About 30% of the terminals surveyed were GABA IR. They were mostly small, although a few of medium size were encountered. The terminals contained either polymorphic or round synaptic vesicles; these occurred in an approximately 5:1 ratio. Most of these terminals formed symmetric synapses with dendrites of various sizes. The GABA-IR terminals also made synaptic contacts with somata of cuneate neurons and axon terminals of unknown origin. In addition, a few GABA-IR terminals forming asymmetric synapses were found in the cuneate neuropil. The possible functional significance of the synaptic organisation is discussed. PMID- 1304579 TI - Biometry of the anterior border of the human hip bone: normal values and their use in sex determination. AB - Sixteen different variables and 3 indices for the anterior border of 42 human hip bones from a Spanish skeletal collection were studied. Values for 15 of these variables and for the 3 indices are reported. We were unable to detect statistically significant differences between means relating to side in any of the variables and indices studied. Statistically significant differences were detected between means in relation to sex for 4 variables (distance from the anterior superior iliac spine to the pubic tubercle, distance from the anterior inferior iliac spine to the iliopubic eminence, distance from the anterior inferior iliac spine to the pubic tubercle, length of the notch between the anterior inferior iliac spine and the iliopubic eminence). These variables could be used for sex determination from the human hip bone or its fragments. PMID- 1304580 TI - A quantitative and morphometric study of the transformation of amoeboid microglia into ramified microglia in the developing corpus callosum in rats. AB - The morphometric and quantitative changes associated with the differentiation of amoeboid microglia into ramified microglial cells in the corpus callosum of rats between 21 d postconception (E21) and 15 d postnatally are described. Using lectin labelling, 5 morphological types of labelled cells (R, SP, KLP, TLP, AP) based on cell body shape, the configuration of their cytoplasmic processes and their staining intensity, were recognised. Round cells (R) and cells with stout processes (SP) were aggregated in the central part of the developing corpus callosum whereas the highly branched labelled cells were distributed at its periphery. When the morphometric data and labelling intensities of labelled cells were analysed with the aid of an image analysis system, the values for cell length, area and perimeter increased as the complexity of branching increased, whereas the lectin-labelling intensity became reduced. Quantitative study showed that the proportion of the different morphological types of lectin-labelled cells peaked at different ages. The sequential peaking of R, SP and highly branched cells with advancing age suggests a similar chronological order of differentiation of R into branched cells. The quantitative study also showed a rapid increase in the density of lectin-labelled cells in the postnatal period between P4 and P8, attributed primarily to the active proliferation of the cell type. The consequent reduction of cell density (after P13) was probably due to cell death, a feature which appeared to increase with development. PMID- 1304581 TI - An immunohistochemical study of human postnatal paraganglia associated with the urinary bladder. AB - Histological and immunohistochemical methods were used to study pelvic paraganglia in a series of human postnatal specimens ranging in age from 1 month to 6 y. Up to 5 months of age, many of the encapsulated paraganglia contained small pacinian-like sensory corpuscles which occurred either singly or in small clusters, implying an unknown functional interrelationship during this period. In older specimens, this intimate association was not observed since pacinian corpuscles and small nonencapsulated clusters of paraganglion cells were observed only as separate structures. It is suggested that the paraganglion cells may induce the formation of the pacinian corpuscles during fetal development. Immunohistochemistry using the nerve marker protein gene product (PGP 9.5) demonstrated a rich plexus of varicose nerve fibres within the paraganglia which may directly innervate the paraganglion cells and/or be associated with the profuse vascular supply. A similar density of vasoactive intestinal polypeptide containing nerves was also demonstrated while some of the nerves contained calcitonin gene related peptide or substance P. The paraganglion cells stained positively for tyrosine hydroxylase, dopamine-beta-hydroxylase and neuropeptide Y, but not for phenylethanolamine N-methyltransferase. This combination of immunostaining confirms them as a rich source of noradrenaline. PMID- 1304582 TI - An investigation of the migratory potential of mouse oocytes in vitro. AB - This investigation was undertaken to determine the potential of mouse oocytes for migratory activity using bisected ovaries in vitro. Bisection allowed larger medullary oocytes to be brought nearer to the surface; in this way the migratory potential of all oocytes could be studied. Observations were made following 48 h culture to allow for recovery from any initial traumatic effects resulting from bisection. Ovaries were explanted from fetuses at d 15 postcoitum and from neonatal and postnatal mice (d 1-7, 11, 12 and 14 of life) and examined by scanning and transmission electron microscopy. Oocytes were extruded from the surface and a sequence of events was inferred. Cells superficial to the oocyte sloughed off, exposing the oocytes which showed the migratory phenotype as they emerged onto the surface. Here each oocyte became rounder and was finally extruded, leaving a 'crater'. Scanning electron microscopy of the explant surface allowed counts to be made of emergent oocytes. The number of explants showing emergent oocytes was at a maximum when ovaries were removed at the end of the first week postnatum; the mean number of oocytes emerging from each also peaked at this time. Numbers of migratory oocytes declined in ovaries aged 11 d at explantation and by d 14 only 66% of explants showed oocytes at the surface. The distribution of oocytes of various sizes at the surface suggests that both small cortical oocytes and larger medullary oocytes can express the migratory phenotype. Transmission electron microscopy verified structural integrity of the emerging oocytes and revealed their relationship to underlying cells. PMID- 1304583 TI - Blood supply of the articular disc of the antebrachiocarpal joint in dogs. AB - The normal vascular anatomy of the articular disc of 48 antebrachiocarpal joints was studied in 24 dogs (12 puppies and 12 adult animals) using an India ink vascular injection technique. It was found that the articular disc receives its blood supply mainly from the palmar and dorsal branches of the palmar interosseous artery. Branches of these 2 arteries arborise and give direct peridiscal vessels to the dorsal, proximal and palmar sides of the articular disc. The peridiscal vessels ramify and anastomose with one another to form a cup shaped terminal peridiscal capillary plexus around the disc which ends at the peripheral parts of the disc in a series of terminal capillary loops. This leaves the major central segment of the disc without blood vessels. The proportion of vascularised to nonvascularised areas of the disc depends upon the age of the animals. In young puppies, the degree of vascular penetration into the disc is quite extensive, while in adult animals it ranges from 15 to 25% of the discal width; the considerably larger central area of the articular disc is thus avascular. PMID- 1304584 TI - Histological features of the dorsal cortex of the third metacarpal bone mid diaphysis during postnatal growth in thoroughbred horses. AB - The dorsal cortex of the equine third metacarpal mid-diaphyseal bone was characterised during growth by the histological and microradiographic examination of specimens from 30 horses ranging in age from 2 months to 8 y. Bone from horses aged less than 6 months was characterised by rapid periosteal apposition of circumferential trabeculae of woven bone that were next connected by radial trabeculae to the parent cortex. Deposition of lamellar bone on the inner trabecular surfaces resulted in rows of primary osteons. Replacement of primary bone occurred only after 4 months of age and preferentially in the woven interstitial bone separating rows of primary osteons formed in the postnatal periosteal cortex. Resorption cavities and incompletely filled secondary osteons characterised bone of 1 and 2-y-old horses. Bone from horses older than 3 y contained several generations of secondary osteons, fewer resorption spaces and incompletely filled osteons, and had a greater portion of circumferentially oriented collagen fibres than bone from younger horses. Bone from horses older than 5 y had large resorption cavities characterised by irregular boundaries. We propose that the process of periosteal bone tissue apposition observed in growing foals be called 'saltatory primary osteonal bone formation' and that this process results in faster cortical expansion and larger total surface area for bone deposition than circumferential lamellar, simple primary osteonal, and plexiform mechanisms of periosteal bone formation. We speculate that bone from 1 and 2-y old horses would be more susceptible to fatigue microdamage resulting from compressive loads because of high porosity, few completed secondary osteons and low proportion of circumferentially oriented collagen fibres. PMID- 1304585 TI - Immune response following vasectomy in the rat: a study of the stimulation of the regional lymph node. AB - Following vasectomy, sperm granulomas are generally believed to be important sites of access of spermatozoal antigens to the immune system. This study tests the validity of that assumption by grafting tissues from a sperm granuloma to an ectopic site (the scrotal skin) and studying the effect on the regional (inguinal) lymph node. Xiphoid cartilage provided the graft material in control animals. The experimental lymph nodes showed significant increases in weight and in the number of sectional profiles of cortical nodules indicating that they were stimulated by the presence of the granuloma tissue. To investigate the mechanism of lymph node stimulation further, a group of rats underwent unilateral vasectomy followed after 7 wk by ipsilateral orchidectomy. Three months after the initial operation the histological features of the regional (left renal) lymph node of the epididymis and granuloma were compared with corresponding nodes from rats 3 months following unilateral vasectomy only and following sham operation. The results indicate that continuous sperm production is required to sustain activity of the regional lymph nodes despite the continued presence of spermatozoa in the sperm granuloma. PMID- 1304587 TI - The peripheral course of the axons innervating the medial rectus muscle within the subarachnoid portion of the oculomotor nerve. AB - There is clinical evidence of topographic localisation of fibres within the oculomotor nerve. It is generally accepted that the pupillomotor fibres have a localised course within the dorsomedial periphery of the subarachnoid portion. However, the precise course of the individual groups of axons innervating each muscle has not been examined in detail. In this study the course of the axons innervating the medial rectus muscle was investigated in the subarachnoid portion of the oculomotor nerve of the rat. The medial rectus muscle was injected with horseradish peroxidase until it was fully infiltrated. The subarachnoid portion of the oculomotor nerve was removed and sectioned longitudinally in the sagittal plane. Sections were reacted with tetramethylbenzidine as a chromogen. Labelled axons were found to be localised in the ventral part of the subarachnoid portion of the nerve. PMID- 1304586 TI - Ultrastructural aspects of oocyte growth in the marsupial Monodelphis domestica (grey short-tailed opossum). AB - The growth of the opossum Monodelphis oocyte does not correspond to the strict biphasic pattern so far described in eutherians and marsupials. The oocyte increases appreciably in size during the last stage of antral follicle development. During the primordial and primary follicle stage Balbiani bodies or paranuclear complexes are not detectable in Monodelphis oocytes. Organelles are randomly distributed. In addition to the nucleolus, perichromatin and ribonucleoprotein particles are other intranuclear structures which occur as regular components in the early Monodelphis oocyte. Clusters of particles are mostly seen in close association with the nuclear envelope. Similar material has been encountered in the cytoplasm as a type of freely-existing 'nuage' material but never as mitochondria-associated 'nuage' or 'cement'. Both types of particles, intranuclear and cytoplasmic, disappear by the time antral follicle formation begins. Mitochondria are at first of the typical transformed shape seen in most mammalian oocytes. They are large, round or oval in outline with a few, often arched, cristae and a light matrix. During the primary follicle stage, mitochondrial size and complexity decrease and the matrix becomes electron dense. A close relationship between mitochondria and endoplasmic reticulum appears early in the primordial and later in the primary follicle oocyte. Regularly detected structures in the ooplasm of preantrum oocytes are paired or 'confronting' cisternae of endoplasmic reticulum, which are lamellar complexes comprised of 2 or more parallel cisternae with intervening electron-dense material. The most conspicuous inclusions in the Monodelphis oocytes of the tertiary and graafian follicles are vesicles. All other organelles are confined to the peripheral zone of the oocyte. Golgi and endoplasmic vesicles both take part in the formation of multivesicular bodies which seems to be the starting point for the vesicle accumulation. Further increase in size involves the incorporation of endocytotic vesicles and the coalescence of larger vesicles. Ordinary fixation procedure leave the vesicles empty. Cortical granules are found only in small numbers. PMID- 1304588 TI - Innervation of an aberrant digastric muscle in the posterior thigh: stratified relationships between branches of the inferior gluteal nerve. AB - During dissection of the gluteal region and the posterior thigh, an aberrant digastric muscle was observed on the right side of a 77-y-old Japanese male cadaver. This originated from the sacrotuberous ligament and inserted into the lateral surface of the long head of biceps femoris. Based on its innervation, this aberrant muscle may be homologous with the femorococcygeus. PMID- 1304589 TI - Unrotated left kidney associated with an accessory renal artery. AB - During routine dissection, a rare anomaly of the kidneys and their vessels was observed in a 55-y-old male cadaver. The anomaly consisted of an unrotated left kidney with partly extrarenal calyces and pelvis. In addition to its normal artery, the left kidney received a branch originating from the inferior end of the aorta. PMID- 1304590 TI - Association of nerve fibres with myoid cells in the chick thymus. AB - The presence of nerve fibres in the medulla of the chick thymus has been investigated ultrastructurally. Unmyelinated nerve fibres were found not only in the perivascular space but also among the myoid cells. The nerve fibres were situated in close proximity to the myoid cells. The unmyelinated axons, containing predominantly clear vesicles and some dense-core vesicles, were found in recesses of the plasmalemma of the Schwann cell. Contacts between nerve fibres and fibroblasts were also observed. PMID- 1304591 TI - An unusual ulnar nerve-median nerve communicating branch. AB - Branching of the ulnar nerve distal to the origin of the dorsal cutaneous branch was investigated in 25 hands in one of which an anatomical variation was observed. This finding may be of importance in the evaluation of certain entrapment phenomena of the ulnar nerve or unexplained sensory loss after trauma or surgical intervention in that particular area. PMID- 1304592 TI - R. Strocchi et al.: The human anterior cruciate ligament--histological and ultrastructural observations: Journal of Anatomy (1992) 180, 515-519. PMID- 1304593 TI - A computerized system for identifying and informing physicians about problematic drug use in nursing homes. AB - With growing concern over the quality of medication use in nursing homes, physicians, administrators, pharmacists, and regulators are looking for effective and efficient methods to improve it. Pharmacy consultation alone appears to be ineffective in controlling the use of inappropriate drugs. We describe here a computerized drug utilization review system designed for use in nursing homes. The system evaluates the appropriateness of medication use by criteria developed through the consensus of experts in geriatrics and specifically designed to address the pharmacological needs of elderly, nursing home residents. The program not only determines the frequency of inappropriate prescriptions, but produces written, educational statements to be given to prescribing physicians. These statements can also be given to nurses to educate them about issues in geriatrics pharmacology. Additionally, the system produces medication order forms that may help focus physicians' attention on the need to evaluate drugs individually. PMID- 1304594 TI - Evaluating productivity in clinical research programs: the National Cancer Institute's (NCI) Community Clinical Oncology Program (CCOP). AB - This paper outlines an approach to studying productivity in clinical research programs that incorporates environmental, organizational, provider, and patient specific factors in the model of production process. We describe how this approach has been applied to the National Cancer Institute's (NCI) Community Clinical Oncology Programs (CCOPs). Next, a practical evaluative model of the productive process in CCOPs is outlined and its use in evaluation and monitoring performance in CCOPs is discussed. Each level of the model is described and a number of factors potentially affecting each level are explored. Finally, we discuss the strengths and weaknesses of this approach and show how management can use it to study and improve the productivity of clinical research programs. PMID- 1304595 TI - Forecasting hospital laboratory procedures. AB - Improved forecasts of hospital laboratory procedures can provide the basis for better resource planning and enhanced operating efficiency. The research reported here-in describes how multiple regression models can be both a source of insight into causal relationships and a tool for achieving accurate monthly forecasts. Past research in this area may have overstated the statistical significance of findings because of a failure to address the potential effect of serial correlation. The present study uses the Cochrane-Orcutt regression procedure, rather than OLS, to overcome this problem. A model using inpatient admissions, acuity days, length of stay, discharge days and seasonal dummy variables is shown to account for 87% of the variation in the number of billable laboratory procedures. A simpler multiple regression model and a Winters' exponential smoothing model were found to provide excellent forecasts for laboratory procedures. In a one year out of sample evaluation, the annual percent forecast error was 0.7% for the regression model. This compares favorably to a percentage forecast error of 11.6% using subjective forecasting methods. PMID- 1304596 TI - Cost justification of a laboratory information system: an analysis of projected tangible and intangible benefits. AB - A pre- and postimplementation comparison of tangible and intangible benefits of the laboratory information system are presented. The key activities projected to save costs through work reduction were evaluated as a basis for procuring a laboratory information system. Following implementation and four years of LIS operation the individual activities used for justification were resurveyed. The tangible benefits which were measured prior to LIS justification totaled $153,471.84 per year based upon fiscal year 1985-86 dollars. The objective re evaluation of these activities four years after implementation and operation resulted in a measured $115,326.93 per year savings. The loss of projected savings is directly related to over estimates in the original justification evaluation and personnel behavior. The intangible benefits projected were all realized including a number of intangible benefits which made a significant impact on several departmental and clinical services at our institution. PMID- 1304597 TI - TCK: a clinical genetics data collection system. AB - This work examines the database design and user interface design for a clinical genetics data collection system known as TCK. A specific design goal is automatic generation of the CORN reports. Emphasis in this paper is on how the logical data model resulting from the database design, and the user interface work together to enforce the enterprise results pertaining to data. Data screens are shown, sample queries are explained and the data mapping to the CORN reports presented. PMID- 1304598 TI - Increase in the activity of alkaline phosphatase by L-ascorbic acid 2-phosphate in a human osteoblast cell line, HuO-3N1. AB - The activity of alkaline phosphatase (ALPase) was significantly enhanced in a human osteoblast cell line, HuO-3N1, when it was cultured in the presence of L ascorbic acid 2-phosphate (AsA-P; a stable ascorbic acid derivative). With AsA-P in the culture, the level of ALPase activity increased approximately 3-fold without any effect on either the morphology or growth rate. This increase was dependent on the AsA-P concentration in the range of 0.2-2 mM and required at least 48 h incubation with AsA-P. The ALPase mRNA level, however, remained rather constant irrespective of the enzyme activity. Removal of AsA-P from the precultured medium decreased the stimulatory effect of ascorbic acid on the ALPase activity, indicating that the effect was reversible. Dexamethasone, an inducer for osteoblastic differentiation, enhanced the level of ALPase activity irreversibly, in parallel with the increase in the level of its mRNA. The enhancement of the ALPase activity by ascorbic acid in this cell line appeared to be independent of cell differentiation. PMID- 1304600 TI - The effect of spiny lobster shell powder on bone metabolism in ovariectomized osteoporotic model rats. AB - Calcium has been found to be indispensable in the prevention of osteoporosis. Recently, there has been a great deal of research into the best way to consume calcium. In this study, the effect of "powdered lobster shell" on bone metabolism was examined in ovariectomized osteoporotic model rats. This powder has a good flavor and taste, and contains high quantities of calcium. Six-week-old SD-strain female rats were ovariectomized and were fed a low Ca diet (0.01% Ca and 0.3% P) for 32 days. Thereafter, the rats were divided into two groups; the control group was fed a control diet (0.3% Ca and 0.3% P) and an experimental group, the lobster group, was fed a lobster shell powder diet (0.3% Ca and 0.3% P) ad libitum for 30 days. The results were as follows: in comparison with the control group, the lobster group had significant increases in (1) bone mineral density [BMD (DEXA Hologic's QDR-1000] of lumbar spines and tibial proximal metaphyses, which are mainly trabecular bones, and BMD of tibial diaphyses, which is a mainly cortical bone, (2) the breaking force and energy of femur. These results suggests the lobster shell powder could be a valuable source of dietary calcium in increasing BMD, breaking force and energy in osteoporotic model rats. PMID- 1304599 TI - Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse. AB - The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse. PMID- 1304601 TI - Enhanced phagocytosis of rat alveolar macrophages by intravenous infusion of an arginine-enriched solution. AB - Phagocytosis of rat alveolar macrophages (AM) was enhanced by the infusion of arginine-rich solution for 7 days. The enhancement of phagocytosis by arginine rich solution was due to not the difference in the distribution of AM subpopulations (I to IV) but the difference in phagocytic activity of AM in fraction IV. In the process of phagocytosis, there were no significant differences in the stages of migration, attachment, and digestion between control and arginine-rich solutions, although AM from fraction IV of rats infused with arginine-rich solution showed significantly higher ingestion of opsonized sheep red blood cells (SRBC) compared to that of control group. Furthermore, the production of macrophage-activating factor (MAF) from rat splenocytes was higher in arginine-rich group than that of control group. AM from fraction IV of rats fed a stock diet had a higher arginase activity and showed a significant increase of phagocytosis following in vitro incubation with L-arginine (25 and 50 mM) for 24 h. From these results, the enhanced phagocytosis of AM by arginine-rich solution may be due to the increased phagocytosis of AM from fraction IV, in which the higher sensitivity of AM from fraction IV to arginine and the higher production of MAF from splenocytes following the infusion of arginine-rich solution participate. PMID- 1304602 TI - Role of active oxygen species in the toxic effects of glucosone on mammalian cells. AB - Glucosone (D-arabino-hexos-2-ulose), a typical enediol product formed both in the Maillard reaction and gamma-radiolysis of sugars, decreased survival of Chinese hamster lung V79 cells, which were incubated under MEM for 4 h. Inhibition of the decrease in cell survival by catalase and SOD suggests the role of active oxygen species, namely H2O2 and O2-, in the biological effects of glucosone. H2O2 was formed in the medium during oxidative degradation of glucosone. Inhibition of the formation of H2O2 by SOD indicates that the formation of H2O2 and the consequent decrease of the cell survival was enhanced by O2-. These results suggest that the mechanisms of the effects of glucosone on the mammalian cells in the absence of Cu2+ are different from those in the presence of Cu2+. PMID- 1304603 TI - Intake of iodine and major nutrients in an area of endemic goitre. AB - We surveyed the diet of a group of inhabitants in a mountainous area where goitre was endemic. The amount of iodine supplied by the diet was determined by analyzing foods with gas chromatography with electron-capture detection. The mean daily intake of iodine per person was between 286.4 and 1,134.4 micrograms. These values are within acceptable ranges recommended by several authors. The dietary supplies of proteins, fats and carbohydrates were also all within the ranges recommended by the FAO/WHO. Although goitre was endemic in the area studied, no dietary deficiency in iodine supply was found in any of the families investigated. Thus the ultimate cause of the endemic will have to be sought in other etiologic factors. PMID- 1304604 TI - Effect of dietary chitin on cholesterol absorption and metabolism in rats. AB - The effect of chitin at the level of 5% in the diet on cholesterol absorption and metabolism was studied in Wistar rats fed on diet containing beef tallow (7%) and cholesterol (1%). When compared with pair-fed controls, rats fed on diet containing chitin had: (1) similar weight gain and feed efficiency, (2) lower apparent protein digestibility, (3) equivalent liver steatosis, (4) reduced levels of liver triglycerides and cholesterol, (5) similar levels of serum and fecal cholesterol, (6) higher excretion of triglycerides in feces. PMID- 1304605 TI - The effect of dietary safflower phospholipid on steroids in gastrointestinal tract of rats fed a hypercholesterolemic diet. AB - The effect of dietary safflower phospholipid (Saf-PL) on the postprandial changes of steroids in the small intestinal and cecal contents was examined in rats fed a hypercholesterolemic diet. The triglyceride mixture (SP-Oil) containing a comparable amount of linoleic acid to Saf-PL was used as a reference fat source. Saf-PL suppressed the elevation of plasma cholesterol levels at all times after meal intake, when compared to SP-Oil. The reduction of plasma cholesterol in rats fed the Saf-PL diet was exclusively observed both in chylomicron plus very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The rate of gastric emptying was not modified by the Saf-PL diet. The level of neutral steroids in the small intestinal contents was almost comparable in both groups, but in the cecal contents and feces it was significantly higher in rats fed the Saf-PL diet. On the other hand, the level of acidic steroids in the small intestinal contents tended to be higher in rats fed the Saf-PL diet than in those fed the SP-Oil diet, whereas in the cecal contents and feces it was comparable in the two diets. These results suggest that Saf-PL causes the accumulation of neutral steroids in the cecum due to the rapid transit through the small intestine. PMID- 1304606 TI - Cultural variations in premorbid personality of endogenous depression: a transcultural study. AB - The triplet Typus Melancholicus proposed by Tellenbach (1961), endogenous depression, a good response to antidepressants, seems to give a form of clearly defined entity. In this study comparing Typus Melancholicus in Japan and in France, we have tried to differentiate the essential elements which vary according to culture. Thirty-eight patients corresponding to major depression (DSM-III-R) hospitalized in our clinics in Japan and in France and their families have been questioned during and after the pathological episodes using a method of our own devising. In Japan, Typus Melancholicus is generally respected and socially well integrated because of its first characteristic, or "orderliness with consideration to others." For that reason in the premorbid life, it is usually free from manifest conflict, and its personality is remarkably homogeneous. In France the opposite is true with the range of variations being wide with a high frequency of neurotic aspects. This may be due to the malfunction of "the orderliness with consideration to others" in France, where individualism is dominant. We have found two general types of variants, named "hypercommon" and "hypernormative." These two directions correspond to the elements that compose Typus Melancholicus: patients of the first group have a tendency to adapt to other's point of view; patients of the second group have a tendency to be under the pressure of a sense of obligation toward norms. PMID- 1304607 TI - Some nosological considerations on "borderline case". AB - The so-called "borderline cases" are classified nowadays into Borderline Personality Disorder (BPD) or Schizotypal Personality Disorder (SPD) according to DSM-III-R. We discussed them as follows: The common pathology to them is their imaginary relationship to the object of identification. The difference between them is the distance from patients to their object. After presenting a case who is situated midway between the borderline case and neurosis, the pathology of borderline case can be described as a failure of repression. After classifying borderline cases in Japan into hysterical borderline or obsessional borderline, their relationship to hysterical neurosis and to obsessional neurosis are respectively discussed. PMID- 1304608 TI - Social integration and suicide/homicide in Japan and the United States. AB - In Japan, economic factors were associated with the regional variations in suicide rates, unlike the United States where domestic factors (divorces and births) were associated with the regional variations in suicide rates. Homicide rates also had different social correlates in the two nations, indicating the importance of cross-cultural studies for the identification of reliable phenomena. PMID- 1304609 TI - Bulimia nervosa in a pair of male monozygotic twins. AB - This is a report of a pair of male monozygotic twins meeting the DSM-III-R criteria for bulimia nervosa. At the age of 15, both brothers began to diet and suffered from bulimia. They were admitted to psychiatric hospitals and separated. After admission, their clinical course dramatically changed. The differences in their clinical courses and endocrinological data are suggestive as to the roles of environmental and hereditary factors in the etiology of bulimia nervosa. PMID- 1304610 TI - Eating disorder and schizophrenia. AB - Five cases with eating disorders (one case with anorexia nervosa alone, 4 cases with anorexia nervosa and bulimia nervosa) complicated with schizophrenia and 3 cases of bulimia nervosa complicated with schizophrenia were reported. The eating disorders and schizophrenia were diagnosed according to the diagnostic criteria of DSM-III-R. As to the type of schizophrenia, 4 patients were of an undifferentiated type and 4 cases were of a disorganized type. Regarding the prepsychotic personality, 6 of the 8 cases showed schizothyme personality traits. All the patients showed depressive symptoms which are relatively common in eating disorders. In all the patients, significant social or school life difficulties persisted and a resumption of premorbid functioning was not seen. The possibility of an affinity between anorexia nervosa and schizophrenia was discussed. PMID- 1304611 TI - Pseudodementia and delirium in depression: a contribution to psychosomatic medicine. AB - Presenting cases of depressional pseudodementia and delirium, we wish to point out the following points in this report. The patient in depression displays a state of pseudodementia when he is regarded as having senile dementia by the people around him. The depressed patient falls into delirium when he is embarrassed by an unexpected situation. In other words, the patient shows pseudodementia when he is continuously out of the world of daily meaning; he would fall into a disturbance of consciousness when he is suddenly put out of the world of meanings. This principle is applicable not only to depression but also to all mental diseases. In mental diseases, the symptoms themselves have some meaning for the patient. However, when the patient is put out of the world of ordinary meaning, mental disease presents the aspect of a somatic disease such as dementia or disturbance of consciousness. PMID- 1304612 TI - Influences of prolonged bed rest and cognitive impairment on nursing home residents. AB - Seventy nursing home residents with and 87 without cerebrovascular diseases (CVD) were examined by the modified Stockton Geriatric Rating Scale (modified SGRS) which measures four aspects of impairments; physical disability, socially irritating behavior, communication failure and apathy. They were divided into 3 subgroups according to walking ability; prolonged bed rest, walking with aids and walking by themselves in both groups. Physical disability of mental decline was significantly aggravated more than that of normal intelligence in all the subgroups. Although communication failure and apathy of mental decline had deteriorated more than those of normal intelligence in prolonged bed rest in residents without CVD, apathy of the former had deteriorated more than that of the latter in walking by themselves in residents with CVD. PMID- 1304614 TI - Accelerated plethysmogram in nursing home residents. AB - To investigate the peripheral blood circulation, 24 young volunteers, 28 nursing home residents with cerebrovascular diseases (CVD) and 42 residents without them were studied for accelerated plethysmogram (APG). Both residents were rated by the modified Stockton geriatric rating scale (modified SGRS) which have four aspects of impairments; physical disability, socially irritating behavior, communication failure and apathy. As to the waveform patterns of APG, the majority of the young volunteers and both the residents showed patterns B and G, respectively. Coefficient of APG (Co-APG) of the former was significantly larger than that of the latter. In the residents without CVD, Co-APG was significantly negatively correlated with physical disability and apathy of the modified SGRS. But, Co-APG did not correlate with the modified SGRS in the residents with CVD. PMID- 1304613 TI - An epidemiological study on hyponatremia in psychiatric patients in mental hospitals in Nara Prefecture. AB - Hyponatremia occurs often in mental illness. The frequency was not noticed because of the uncharacteristic symptoms of mild hyponatremia. Of the 1,114 psychiatric inpatients retrospectively surveyed, 10.5% had hyponatremia. Not only patients with schizophrenia, but also patients with other mental illness, especially with epilepsy, having hyponatremia were confirmed. An early onset, a long duration of psychiatric disorder and a prolonged admission were statistically significant factors. Nicotine abuse was not a significant factor. It was suggested that the pathogenesis of hyponatremia in psychiatric patients might be involved in a chronic course of psychiatric disorders and poor response to psychopharmacotherapy. PMID- 1304615 TI - Changes in personality and emotion following bilateral infarction of the posterior cerebral arteries. AB - Remarkable changes in personality, emotion and behavior were observed in a 66 year-old female with bilateral infarction of the medial inferior portion at the temporo-occipital region. Aggressiveness, emotional lability and indifference were noted in the patient as psychiatric manifestation. No definite delirium, however, was observed. A neuroradiological examination revealed the lesions located at the territory of the posterior cerebral artery, which involved the hippocampus, the parahippocampal gyri, the fusiform gyri and the lingual gyri. Therefore, the psychiatric disturbances and the neuropsychological symptoms presented here are attributed to these lesions with the multiple infarctions in the brain. The present case is noteworthy for its unique changes in personality and emotion which in the literature have not reported to be caused following the vascular accident of the bilateral posterior cerebral artery. PMID- 1304616 TI - Comparison of thyroid function between responders and nonresponders to thyroid hormone supplementation in depression. AB - The serum levels of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5' triiodothyronine (reverse T3, rT3) were examined from 8 depressed patients who did not maximally benefit from conventional antidepressant therapy. Four of the 8 depressed patients showed significant clinical improvement after thyroid hormone was added to their ongoing antidepressant drugs. The T4 and rT3 levels prior to thyroid hormone supplementation were significantly lower in responders than in nonresponders, although within the normal range. Furthermore, all of the patients who had both their rT3 levels less than 200 pg/ml and T4 levels less than 7 micrograms/dl responded to the thyroid hormone treatment. These data suggest that the lower T4 and rT3 levels can predict the treatment response to the thyroid hormone supplementation in depressed patients. PMID- 1304617 TI - A retrospective study on delirium type. AB - The clinical features of delirium type were retrospectively studied to characterize a delirium type in consecutive 106 patients. The subjects suffered from 15 medical diseases and were grouped into hyperactive, hypoactive and mixed types according to their cardinal features. The incidence of delirium was the highest in 70-year-old subjects and there was a gender effect in all the subjects. A decade effect was present in the outcome, delirium type and delirium duration. The delirium type was associated with age at the delirium onset, outcome and underlying disease. The incidence of hypoactive type correlated with that of mixed and hyperactive types, and a high rate of full recovery in the hyperactive type and a high rate of death in the mixed type were noted. The increase in incidence of the mixed type and the decrease in incidence of the hyperactive type contributed to a poor outcome. Malignancy, hepatic, cerebrovascular and bone and joint diseases highly correlated with the occurrence of delirium. PMID- 1304618 TI - Shortening of N1 and P3 latencies in event-related potentials observed coincidentally with clinical improvement during nootropic medication in a demented patient: specific effect of nicergoline. AB - Event-related potentials, measured eight times in a patient in the early stages of dementia, demonstrated that clinical symptoms, especially loss of motivation, improved coincidentally with a shortening of reaction time, N1 latency, and P3 latency during nicergoline medication among three nootropics prescribed. Such a longitudinal study design was considered to be useful for quantifying and objectively comparing effects of various nootropics noninvasively. PMID- 1304619 TI - Decreased superoxide dismutase activity in erythrocyte in Parkinson's disease. AB - Superoxide dismutase (SOD) activities in Parkinson's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a significant correlation between SOD activities and the duration of illness in the treated PD group (p < 0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group. PMID- 1304620 TI - Validity of electrode placement at Fpz to detect alpha wave. AB - The possibility on placing electrodes at Fpz-A2 instead of C3-A2 was investigated to obtain a more stable configuration avoiding obstruction by the hair. Our original system of alpha wave detection by a microcomputer was used, and a total of 22 all-night hypnograms of five healthy young students was recorded. Pearson's moment correlation coefficients of alpha wave % between the two positions were 0.780-0.948. Except for one subject, alpha wave % taken at Fpz-A2 tended to be 3 5% lower than that at C3-A2. The above analysis indicates that using EEG electrode position of Fpz-A2 is valid and useful as a stable electrode configuration for a long-time monitoring. PMID- 1304621 TI - Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice. AB - 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime. PMID- 1304622 TI - Synaptosomal membrane fluidity, lipid peroxidation and superoxide dismutase activity in the brain of amygdala-kindled rats. AB - Synaptosomal membrane fluidity, lipid peroxide (LPO) and cytosolic superoxide dismutase (SOD) activity were examined in various brain regions (amygdala, hippocampus, striatum and frontal cortex) of amygdala-kindled rats. At 24 h after the last seizure, a significant increase of membrane fluidity was observed in all the regions examined, whereas the LPO level was significantly decreased in the four regions with enhanced activity of cytosolic SOD. At 7 days after the last seizure, membrane fluidity was decreased only in the hippocampus. At 6 weeks after the last seizure, there were no changes in membrane fluidity between control and kindled rats. These results suggest that membrane fluidity and lipid peroxidation are modulated transiently by a kindled seizure, but not at a steady state of kindling with enduring seizure susceptibility. PMID- 1304623 TI - Lack of effect of haloperidol or methamphetamine treatment on the mRNA levels of two dopamine D2 receptor isoforms in rat brain. AB - In order to investigate whether changes of the two mRNAs encoding the D2 receptor isoforms were induced by chronic haloperidol or methamphetamine treatment in rats, we measured the brain mRNA levels using in situ hybridization histochemistry (ISHH). We used two oligonucleotide probes, an "insert" probe to hybridize with the longer D2 receptor, D2(444), mRNA, and a "spanning" probe to hybridize with the shorter D2 receptor, D2(415), mRNA. Both D2 mRNAs were detected by ISHH in the caudate putamen, nucleus accumbens, substantia nigra, pars compacta and ventral tegmental area. The distributions and the amounts of the mRNAs for the two D2 isoforms did not change after chronic administration of haloperidol (1 mg/kg/day for 14 days, ip) or methamphetamine (4 mg/kg/day for 14 days, ip). These results suggest that the changes of D2 receptor density induced by chronic neuroleptic and psychostimulant treatment are not due primarily to receptor expression. PMID- 1304624 TI - Use of dengue blot in dengue diagnosis: the Malaysian experience. AB - Dengue fever/Dengue haemorrhagic fever (DF/DHF) has been a public health problem in Malaysia with an endemic level of about 7 per 100,000 population per year. In 1990, Malaysia experienced its most severe outbreak of DF/DHF with a record total of 5,590 cases referred to the Division of Virology, Institute for Medical Research (IMR). Of these, 1,880 were confirmed serologically to be DF/DHF. The conventional serological procedure, the Haemagglutination Inhibition (HI) test, for the diagnosis of DF/DHF is cumbersome and causes delay in diagnosis. Another problem associated with the HI test has been that it has often been difficult to obtain a second convalescent serum sample for an accurate diagnosis. This has raised an urgent need to establish a "rapid" test for diagnosis of DF/DHF. As such the authors recently carried out an evaluation of a newly available commercial rapid test, namely, the Dengue Blot Assay (Diagnostic Biotechnology Singapore Pte Ltd). The test is intended for use in laboratory confirmation of dengue virus infection. The evaluation was to determine if the test could be utilised as a routine laboratory test and to establish its sensitivity and specificity. Over 400 samples were tested against the Dengue Blot Assay. Results were checked against an in-house Dengue IgM ELISA and HI assay. Preliminary results indicate that the sensitivity and specificity of the Dengue Blot is satisfactory. Our results also indicate that the Dengue Blot has a useful role to play in a routine laboratory especially since it provides rapid results on single serum samples thereby reducing the workload in a busy diagnostic laboratory. PMID- 1304625 TI - Antibody deficiency with hyper IgM--a case report. AB - A 20-month-old Indian boy presented with recurrent pyogenic infections and failure to thrive. His IgG and IgA levels were low, but his IgM was elevated. He also had undetectable isohaemagglutinin titre and neutropenia, both parameters being poor prognostic indicators in this very rare primary immunodeficiency state -antibody deficiency with hyper IgM. Our patient subsequently succumbed to Pseudomonas aeruginosa septicaemia and meningitis inspite of aggressive antibiotic and intravenous gammaglobulin therapy. To the best of our knowledge, this is the first such case to be documented in Malaysia. PMID- 1304626 TI - The pathology of child abuse. PMID- 1304627 TI - In situ hybridisation: principles and applications. AB - In situ hybridisation (ISH) is based on the complementary pairing of labelled DNA or RNA probes with normal or abnormal nucleic acid sequences in intact chromosomes, cells or tissue sections. Compared with other molecular biology techniques applicable to anatomical pathology, ISH enjoys better rapport with histopathologists because of its similarity to immunohistochemistry. It has the unique advantage over other molecular biology techniques--largely based on probe hybridisation with nucleic acid extracted from homogenised tissue samples--of allowing localisation and visualisation of target nucleic acid sequences within morphologically identifiable cells or cellular structures. Probes for ISH may bear radioactive or non-radioactive labels. Isotopic probes (3H, 32P, 35S, 125I) are generally more sensitive than non-isotopic ones but are less stable, require longer processing times and stringent disposal methods. Numerous non-isotopic labels have been used; of these biotin and digoxigenin are the reporters of choice. Optimised non-isotopic systems of equivalent sensitivity to those which use radioactive-labelled probes have been described. In ISH, finding the optimal balance between good morphological preservation of cells and strong hybridisation signals is crucial. Tissue fixation and retention of cytoskeletal structures, unfortunately, impede diffusion of probes into tissues. ISH sensitivity is also influenced by inherent properties of the probe and hybridisation conditions. Although ISH is largely a research tool, it is already making strong inroads into diagnostic histopathology. It has been applied for the detection of various infective agents particularly CMV, HPV, HIV, JC virus, B19 parvovirus, HSV-1, EBV, HBV, hepatitis delta virus, Chlamydia trachomatis, salmonella and mycoplasma in tissue sections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304629 TI - Immunostaining of formalin-fixed, paraffin-embedded tissues for malignant lymphomas. AB - With the advent of new monoclonal antibodies that are applicable to formalin fixed, paraffin embedded sections, immunophenotyping is becoming increasingly important in the diagnosis and classification of lymphomas. However, multiple factors such as fixation, trypsinization and even type of antibodies used have certain effects on the final outcome of the staining procedure. In this paper we report our experience and the problems encountered in our laboratory when we first tried to establish a workable immunostaining protocol for formalin-fixed, paraffin embedded tissue sections using the immunoalkaline phosphatase technique. PMID- 1304628 TI - Drowning. AB - A body recovered from the water does not necessarily imply that death was due to drowning. The diagnosis of drowning is discussed together with the significance of the "diatom" and biochemical tests. PMID- 1304630 TI - Alpha-1-antitrypsin deficiency in babies with prolonged jaundice. AB - Over a three-year-period, 310 babies with prolonged jaundice admitted to GHKL were studied, to determine the incidence of alpha-1-antitrypsin deficiency as a cause of the problem. Ninety-two babies (29.7%) were found to be alpha-1 antitrypsin deficient. The percentage incidence was found to be highest in Indians (33.3%), followed by Malays (31.9%) and Chinese (26.7%). There was a male preponderance with a M:F ratio of 1.6:1. Most of these babies presented at the hospital at the age of more than two weeks but less than one month. Apart from the problem of prolonged jaundice and alpha-1-antitrypsin deficiency, 2 had associated bleeding problems, 11 associated infections and 3 respiratory problems. Two babies had clinical features of Down's syndrome, 2 had G6PD deficiency and 1 had congenital hypothyroidism. AST, ALT and ALPO4 were high in 20, 26 and 3 babies respectively. PMID- 1304631 TI - Antimicrobial resistance: patterns and trends in the National University Hospital, Singapore (1989-1991). AB - The commonly isolated organisms, Staphylococcus aureus, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Acinetobacter species, Proteus species and Enterobacter species from clinical material other than blood, cerebrospinal fluid and stool, were analysed for their incidence and increasing trends of resistance to the commonly used antimicrobials. Staphylococcus aureus was tested against penicillin, methicillin, erythromycin, gentamicin and co trimoxazole; Pseudomonas aeruginosa against amikacin, ceftazidime, gentamicin, piperacillin and cefsulodin; and gram negative bacilli against ampicillin, co trimoxazole, cephalexin, cefuroxime, ceftriaxone, nalidixic acid and nitrofurantoin. Methicillin sensitive Staphylococcus aureus exhibited a high degree of resistance to penicillin only (83%), but methicillin resistant Staphylococcus aureus (34-46%) showed nearly 100% resistance to all drugs tested except for co-trimoxazole over the period of study. A high incidence of resistance was found among Klebsiella species, Enterobacter species, Acinetobacter species and Pseudomonas species. Increasing trends of resistance against cephalosporins were noticed with respect to Acinetobacter species, Klebsiella species and Enterobacter species for cefuroxime and ceftriaxone; Pseudomonas aeruginosa for ceftazidime and cefsulodin. The overall resistance of organisms is notably high. Methicillin-resistant S. aureus is endemic and accounts for about 39% of all S. aureus isolates. The typical nosocomial organisms like Acinetobacter species and Klebsiella species are increasingly developing resistance to useful drugs such as gentamicin, cephalexin and ceftriaxone. PMID- 1304634 TI - [Radio-cinematographic study of active elevation of the prosthetic shoulder]. AB - In order to verify whether it is possible to reproduce the physiologic anterior elevation of the shoulder with a non constrained Neer type prosthesis, the authors have examined the dynamic comportement of 21 total shoulder arthroplasties. Recording of anterior active elevation with video-fluoroscopy and evaluation glenohumeral motion and scapulothoracic motion allowed to distinguish 3 types of biomechanics after total shoulder replacement. A first group of prosthesis (4 cases) had normal biomechanics with conservation of a normal scapulohumeral rythm. This concerned arthroplasties performed for necrosis or osteoarthritis with no cuff tear or loose bone stock and no technical error. A second group of prosthesis (10 cases) had an abnormal biomechanics. There was a superior excursion of the humeral head prosthesis without real glenohumeral motion. A more severe pathology (cuff tear arthropathy, rheumatoid arthritis, old traumas) with bone and/or muscular destruction was sufficient to explain this elevation possible only because of the scapulothoracic motion. Finally, there was a third group of prosthesis (7 cases) which had a reversed scapulohumeral rythm: there was less motion between the prosthetic components but the scapulothoracic motion was unchanged. Three factors can be responsible for this reversed scapulohumeral rythm: 1) The initial pathology, because of the difference in the cuff trophicity. 2) The surgical technic because of the difficulties to respect the position of the joint line and the lever arms. 3) The prosthesis itself, because of the higher degree of conformity and stability between the prosthetic components. PMID- 1304635 TI - [Prevention of scar formation by polyglactin 910 (Vicryl) mesh after lumbar laminectomy in the rat]. AB - Laminectomy in lumbar spine surgery often produces disabling adhesive arachnoiditis. We have tested, on the rat, polyglactin 910 mesh with collagen or not, with a mail 0.9 mm large. We have used 34 Wistar male rats. L5 laminectomy were realised on all the rats. Rats were ranged in four groups: group 1: control, L5 laminectomy alone, 6 months follow up--group 2: one month follow up, L5 laminectomy, vicryl mesh with collagen or not--group 3: two months follow up, L5 laminectomy, vicryl mesh with collagen or not--group 4: six months follow up, L5 laminectomy, vicryl mesh with collagen or not. On 28 rats, the histologic study have demonstrated: group 1 control: important and adhesive fibrosis scar--group 2: no or minimal reaction--group 3: fibroblastic or few cellular, non or little adhesive fibrosis--group 4: moderate adhesive fibrosis in half of the cases with vicryl mesh without collagen, minimal non adhesive fibrosis with collagen vicryl mesh. PMID- 1304636 TI - [Excision of the proximal row of the carpal bones. Apropos of 21 patients]. AB - Twenty one patients have been reviewed with a mean follow-up of 4.6 years. If we except one acute case, the main indications were scaphoid pseudarthrosis (13 cases), Kienbock's disease (4 cases), carpal instability (3 cases) all accompanied by wrist arthrosis. The results were considered excellent and good in 65 per cent of the cases. Pain was improved in 90 per cent of the patients. Average mobility was 71 degrees (76 degrees before operation). Strength was improved in 19 per cent of cases but remained less than the normal side in 60 per cent. Among 15 manual workers 11 went back to the same work and 4 to an adjusted work. PMID- 1304637 TI - [Surgical treatment of rotator cuff rupture. Prognostic factors]. AB - A retrospective study of 67 total ruptures of the rotator cuff operated on was carried on, with an average follow-up of 25 months. The lesions were characterised by their size (19 tears of less than 2 cm, 30 between 2 and 4 cm, 18 over 4 cm) and location (27 tears of the supraspinatus, 15 tears of the supraspinatus extending to the front (coraco-humeral, long biceps, subscapular), 20 supra and infra-spinatus, 5 "massive" tears). The tendon of the long biceps was pathological in half of the cases. Fourteen patients presented with a subacromial osteoarthritis. All patients benefited from a decompression and repair of the rupture. Whereas the subjective results indicate 92 per cent satisfied patients, from the objective point of view the average score with Constant's rating was 62.5 pts with 53 per cent favorable results. Evaluation of force was a particular subject of attention: the results obtained with three charts were compared; the conclusion was in favour of an objective measurement using a dynamometer but with a weighting according to age and sex. The characteristics of the tear (location especially), the state of the long biceps, the presence of a subacromial osteoarthritis and the pre-operative mobility affected statistically and significantly the final result. The authors reserve reconstructive surgery for tears without osteoarthritis, isolated lesions of the supraspinatus having the best prognosis. The existence of a subacromial osteoarthritis, always a sign of a massive tear, in elderly patients should lead one to choose a procedure a minima under arthroscopy. PMID- 1304638 TI - [Role of tibial-fibular grafting in the treatment of infected pseudarthrosis of the tibia]. AB - The author presents a series of 112 patients, suffering an infected fracture or nonunion of the tibia, and operated on by intertibio-fibular grafting (ITFG), between 1960 to 1990. 110 of them were followed up during average 5 years. Some points of the technic are detailed. The whole treatment associates immobilization, antibiotherapy, cleaning procedures and eventually complementary grafting. All patients were consolidated, 73 after ITFG alone, 13 by association, in the same stage, of an open cancellous filling, following Papineau technique. 24 needed a complementary grafting, among them 7 because a technical flaw. 5 iterative fractures were observed, only one of them has not united. 96 patients were cured of any sepsis, most often by associated cleaning procedures, achieved either before or after ITFG. It existed 14 persistent draining sinus, but only 4 may be considered as real failures. The involvement of the ankle joint was unfortunately quite frequent, but it did not seem to be the consequence of the synostosis, but rather of the duration of immobilization. After review of the literature, the other methods of treatment were discussed, particularly these of Papineau and of Ilizarov. The conclusion was that each method has indications, but the ITFG must keep the largest place, being indicated in about two cases out of three. PMID- 1304639 TI - [Grice subtalar arthrodesis: a long-term follow-up in poliomyelitis sequelae]. AB - A retrospective review was done of 19 poliomyelitis feet on which the standard Grice subtalar arthrodesis was performed for correction of valgus feet deformity. The average time of follow-up was 12.1 years. Seventy-nine per cent of the feet had satisfactory results, and all the failures were due to technical errors of graft placement. The calcaneo-first-metatarsal angle on the standing lateral radiograph was found to be the most objective angle and correlated best with the clinical results. The long term effects on the rest of the foot was negligible, with only 3 of the 10 feet, with a follow-up longer than 12 years showing minimal talonavicular arthritis and only 1 ankle developing a ball and socket joint. Ankle valgus was not a significant problem. PMID- 1304640 TI - [Treatment of subcutaneous ruptures of the Achilles tendon by percutaneous tenorraphy]. AB - Since 1982, the authors have progressively settled a technique to repair the calcaneal tendon, the result of which is a percutaneous tenorraphy exclusively used for more than 2 years. Their study includes 28 cases between 1989 and 1992, with an average post operative time of 15.6 months. The technique is fully described, its aim was to restore a normal length of the ruptured tendon in placing together the 2 tendinous ends during the required time to obtain natural regeneration of the Achilles tendon. It reduces the theoric immobilization time, makes rehabilitation easier as well as the return to sportive and professional activities. The suture was percutaneously made with a special material: A Dacron yarn with a 5 mm wide hook set on a 12 long flexible needle. The results were globally good and only very few complications were observed. PMID- 1304641 TI - [Bilateral Kienbock's disease in adolescents. Apropos of a surgically treated case]. AB - The authors report a case of bilateral idiopathic stage III Kienbock's disease. Treatment was surgical and consisted in a shortening osteotomy of the radius, with excellent clinical results. X-rays showed that osteonecrosis was stopped and both lunate bones were gradually remodelled. PMID- 1304642 TI - [Unilateral tibia vara in young children caused by focal fibrocartilaginous dysplasia. Apropos of 4 new cases]. AB - The authors report 4 cases of tibia vara associated with focal fibrocartilaginous dysplasia observed in 3 boys and 1 girl between the ages of 11 and 17 months. Deformation was usually discovered when the child began to walk. It can worsen during the first years of life, thus explaining that two subjects were operated at 3 years and at 4 years and 8 months, with osteotomy for valgus rotation. The outcome was good. The other 2 recovered spontaneously. The authors discuss the diagnostic and pathophysiological problems in the light of the data in the literature and confirm that correction is usually spontaneous, which justifies refraining from treatment. PMID- 1304643 TI - [Management problems of cystic fibrosis in adults]. PMID- 1304644 TI - [Reliability and reproducibility of 3 peak flowmeters determined in a population of primary school children]. AB - Peak-flow measurement increasingly seems to be very useful for routine monitoring of asthma in children. The purpose of this study was to evaluate the reliability and reproductibility of three different peak-flow meters: Miniwright, Vitalograph and Assess. This prospective study was conducted in 100 primary school children aged from 6 to 11 years. In each child, 9 measurements of expiratory peak-flow rate (EPF) were performed with these 3 peak flow meters in a random order. Reproductibility was assessed for each instrument by the greatest divergence observed between the 3 EPF values measured in the same session. Reliability was assessed by comparison between the values obtained with each instrument and theoretical EPF values calculated from a formula which included age, sex and size. Our study validated the reliability and reproductibility of the 3 peak flow meters studied. EPF values were more scattered and less reproductible with Assess, but the difference was not significant. PMID- 1304645 TI - [Perceptions of consequences of chronic respiratory insufficiency in subjects over 65 years with home respiratory assistance. Apropos of 85 patients]. AB - Chronic respiratory diseases (C.R.D.) induce changes in daily activities and mood for the patients who require respiratory assistance (oxygen delivery or ventilation). The aim of this study was to compare physical and social consequences of this disease. A self administered questionnaire was sent to one hundred patients, over sixty five years of age, who were affiliated with the "Association Limousine d'Aide aux Insuffisants Respiratories" (A.L.A.I.R.). The mean age was 72.4 +/- 0.66 (65-92), the mean PaO2 was 54 mm Hg +/- 0.2 (39-76). C.R.D. was stable during the study and treatments did not change. The questionnaire was composed of four scales and twenty-eight subjects; each item was weighed for importance. Subjects included: symptoms, mood, sleep, relationships with their wife or family, home activities. Eighty-five questionnaires were analysed. Reproductibility was good (92%) and non-responses to some questions was less than 10%. Coherence between the scales and the twenty eight items was poor. Regression linear analysis found that only dyspnea was correlated with PaO2 (p < 0.007). For patients, the most important items were: abnormalities of home activities (37%), dyspnea (38%), relationships with their wife (39%) or family (45%), dependence (52%) and perception of A.L.A.I.R. (77%). Quality of life is an important concept for these patients with C.R.D. versus clinical symptoms. Perception of respiratory assistance is very good. PMID- 1304646 TI - [Community-acquired pneumonia in healthy adults: 188 patients treated with spiramycin in private practice]. AB - One hundred and eighty eight outpatients with community acquired pneumonia have been treated by spiramycin in general practice. Community acquired pneumonia was defined by the association of fever > or = 38 degrees C, respiratory symptoms as cough, sputum production, dyspnea or thoracic pain, and pulmonary opacity on the chest X-Ray. The mean age of patients was 44.7 +/- 16.6 and few of them had concomitant chronic illness, as cardiovascular (9%) or bronchopulmonary disease (9%). Twenty one percent of patients have been included after a previous antibiotherapy failure. In 92% on these cases, prior antibiotherapy was a beta lactam. At inclusion, the fever was greater than 39 degrees C in 56% of patients, 58% had localized crepitations at the chest auscultation. The chest X-Ray was performed 1.4 +/- 2.1 days after inclusion and showed a lobar consolidation in 77%. One third of patients presented a clinical picture evoking acute bacterial pneumonia. One hundred and seventy one patients have been reviewed for a second evaluation 4 +/- 1.5 days after inclusion. One hundred and eighty seven patients have visited for the long term follow up 19 +/- 6.5 days after the onset of treatment. Ninety six per cent of them have consulted with a control chest X-ray. At this visit, the antibiotherapy was changed in 2 other patients with of failure. Overall, 83% of patients were clinically and radiologically cured by Spiramycin 3 MU twice a day for 13 +/- 3.5 days. Fourteen percent of patients were improved without necessity of changing the antibiotic regimen. This study confirms the efficacy of spiramycin in the management of community acquired pneumoniae in general practice, either in first line therapy of after the failure of beta lactam. PMID- 1304647 TI - [Loeffer's syndrome: is Taenia responsible?]. AB - Taenia saginata is a parasite of the gastrointestinal tract which is often encountered in France. Its responsibility in the occurrence of pulmonary eosinophilic infiltrates is only exceptionally suspected. We report a case of Loeffler's syndrome most probably caused by Taenia saginata. This case illustrates the diagnostic problems encountered to determine the responsibility of this cestode. PMID- 1304648 TI - [Pseudotumoral form of bronchial tuberculosis]. PMID- 1304649 TI - [Tuberculosis of bronchi and lymph nodes mimicking cancer in a patient with HIV infection]. PMID- 1304650 TI - [Pneumothorax: a rare complication of the treatment of bronchogenic cancer]. PMID- 1304651 TI - [9th Consensus Conference on Resuscitation and Emergency Medicine. 19 June 1992. Evaluation of ventricular function in adults at the patients's bedside]. PMID- 1304652 TI - Anatomical study of preaxial polydactyly in 158 hands. AB - Preaxial polydactyly is a common congenital hand anomaly. Here in 138 patients with 158 duplicated thumbs, a new classification of this anomaly was done from analysis of radiographs and operation records. Initially all the duplicated thumbs were arranged into from Type I to VII on the basis of radiological extent of bifurcation. Appendage type was noted as a separate entity. Type IV was found the most common and had 53 thumbs (33.6%) involved. But findings on surgery indicated that the exact level of bifurcation varied in each type, and Type VII became three times as frequent as previously noted from x-ray examination at the time of surgery. Radiologically encountered duplications at IP (Type II), MP (Type IV) and CM (Type VI) joints were specifically classified into five groups from A to E on the basis of the structural changes detected on surgery. Details in each group were discussed. PMID- 1304653 TI - Characterization of human thymic lymphocytes forming rosettes with stromal cells. AB - The interaction of thymic lymphocytes and stromal cells is believed to be important for T cell development in thymus. In this study, thymic rosettes (TR), which are cell-cell complexes of thymic lymphocytes and stromal cells, were isolated from human thymic tissue, and were characterized. Treating human thymus with collagenase in mild condition, human TR were successfully isolated. Subsequently, TR were purified by the 1G sedimentation method. Human TR consisted of a stromal cell in center surrounded by lymphocytes. The stromal cells were positive for CD14, CD11b, and HLA-DR but negative for thymic epithelial cell specific mAb, UH-1, suggesting that they are macrophage/dendritic cells. The lymphocytes which formed TR (TRL) were mainly double positive (CD4+CD8+) and CD1+ cells, and few of them expressed bright CD3, indicating that TRL are in the intermediate maturation stage. TRL expressed activation markers (Ta1 and HLA-DR) in a significantly higher percentage of cells than did unselected thymocytes. Blocking test revealed that CD11a and CD2 are involved in the binding of TRL and the stromal cells as adhesion molecules. PMID- 1304654 TI - Anesthetic influences on myocardial and hepatic energy metabolism in hemorrhaged spontaneous hypertensive rats. AB - Twenty four spontaneously hypertensive rats (SHRs) were used to assess the influence of anesthetics on myocardial and hepatic energy metabolism after hemorrhage. They were divided into four groups: a control group and three others which received pentobarbital (60 mg.kg-1 ip), 2.2% enflurane, or 1.4% isoflurane. Following a 10-min stabilisation period, blood (2 ml.100 g body weight-1) was gradually withdrawn over a 5-min period from a femoral artery. Thirty minutes after the induction of hemorrhage, the heart and liver were removed, and myocardial and hepatic metabolites (ATP, lactate, pyruvate, and glycogen) were measured by the enzymatic methods. Metabolic acidosis and decreased hematocrit were noted in all groups after hemorrhage. The mean arterial pressure in rats receiving anesthetics decreased significantly in comparison with the control group. There were significant increases of myocardial and hepatic lactate/pyruvate ratios in rats receiving enflurane when compared with controls. These results suggest that enflurane may be more detrimental than other anesthetics to the maintenance of anesthesia in hypovolemic SHRs. PMID- 1304655 TI - Polysaccharide-coated liposomal amphotericin B for the treatment of murine pulmonary candidiasis. AB - Amylopectin-coated liposomal amphotericin B was investigated in a murine model of pulmonary candidiasis. The LD50 of amylopectin-coated liposomal amphotericin B in normal mice was more than 10.0 mg/kg, and that of conventional amphotericin B was 1.2 mg/kg. Amylopectin-coated liposomes showed twice the concentration in the lungs of conventional liposomes. Candida albicans was inoculated intratracheally into BALB/C mice. Twenty-four hours later, the number of Candida in the lungs of mice treated with amylopectin-coated liposomes was less than in those treated with conventional liposomes, and amylopectin-coated liposomes improved the survival rate of inoculated mice. Coating liposomes with amylopectin aids the targeting of amphotericin B to the lungs. PMID- 1304656 TI - Synovial fluid ferritin in traumatic hemarthrosis, rheumatoid arthritis and osteoarthritis. AB - Synovial fluid ferritin levels in patients with traumatic hemarthrosis (HA), rheumatoid arthritis (RA), and osteoarthritis (OA) were measured by double antibody radioimmunoassay. Synovial fluid ferritin levels were significantly higher in 60 patients with HA (mean +/- S.D., 536 +/- 536 ng/ml) and 39 patients with RA (614 +/- 486 ng/ml) than in 20 patients with OA (130 +/- 119 ng/ml) (p < 0.01). Individual levels, however, considerably varied. In HA patients, the synovial fluid ferritin level correlated well with the duration of hemarthrosis, but not with hemoglobin, hematocrit, or an inflammatory synovial fluid index such as the leukocyte count. In RA patients, there was no significant correlation between the synovial fluid ferritin levels and any inflammatory parameter, such as catalase activity, synovial leukocyte counts (including polymorphs and monocytes) or the duration of arthritis. Our results indicate that the synovial fluid ferritin level reflects primarily hemoglobin degradation and appears unrelated to inflammation in joint diseases. PMID- 1304657 TI - An improved method of bronchial stump closure for prevention of bronchopleural fistula in pulmonary resection. AB - We performed 880 pulmonary resections from January 1982 to June 1988 using Sweet's procedure for closure of the bronchial stump, in which 39 patients (4.4%) developed bronchial fistulas. Bronchoscopic studies showed that bronchopleural fistulas were located mainly at the corner of the stump. This indicates that the corner is the point with the highest tension when Sweet's procedure is employed. In some cases, stumps were injured by suture materials, resulting in bronchopleural fistulas. Since July 1988, bronchial stumps have been closed by using two pairs of teflon pledgets with additional interrupted sutures. From July 1988 to April 1990, 288 patients were treated by this new method, and only one of them developed bronchopleural fistula. This new method prevents injury of the stump by suture material and reduces the tension at the bronchial stump for a long time. Thus, pulmonary resections can be safely employed even after anti cancer chemotherapy and/or radiation therapy. PMID- 1304659 TI - Reproduction of pigs in the hills of eastern Nepal. AB - A survey of 101 farmers with sows was conducted in the Koshi Hills of Nepal. Estimates of those reproductive traits which did not differ significantly between local and Pakhribas crossbred sows, are farrowing interval 7.4 months, litter size at birth 8.3, age of piglets at weaning 2.2 months and total number of farrowings 13.2. Local pigs reach sexual maturity sooner than Pakhribas crossbreds; age at first farrowing for the two genotypes is 10.7 and 12.0 months (P < 0.05), and age at first mating of boars is 6.5 and 7.4 months (P < 0.05). Sows farrow throughout the year and there is no clearly defined best season for farrowing. Pre-weaning mortality rates are estimated to be 22% for local piglets and 15% for Pakhribas crossbreds. Almost all farmers practise controlled mating in which either the sow is taken to the boar or the boar is brought to the sow. The proportion of farmers (with sows) who own a boar is only about 5 per cent. PMID- 1304658 TI - Effects of an anthelmintic treatment programme on sheep productivity in the Middle Atlas, Morocco. AB - This study evaluated the production advantages of the strategic anthelmintic treatment of both lambs and ewes in an area endemic for gastro-intestinal nematodes, lungworms and liver flukes. The liver fluke infections were generally chronic. The lambs were treated with albendazole (SmithKline Beecham), fenbendazole (Hoechst Roussel) or a vitamin supplement and their weight gains were followed over the next 7 months. The control group, which received a vitamin supplement only, gained 6.67 kg from July to January. The group that received fenbendazole, an anthelmintic with no activity against liver flukes, gained 10.42 kg over the study period. The third group which received albendazole, an anthelmintic with efficacy against liver flukes, gained 13.07 kg over the same period. Lamb deaths apparently due to liver flukes were 12, 4, and zero for the control, fenbendazole and albendazole groups, respectively. Similar advantages were observed in the ewes. Deaths were 16, 8, and zero in the control, fenbendazole and albendazole groups, respectively. The lambing rate in the control group was significantly lower than that in either of the 2 treated groups. The number of services per conception was significantly lower in the albendazole treated group than that in either of the other groups. These studies demonstrated the advantages of anthelmintic treatment in sheep in a helminth endemic area. While removing gastro-intestinal nematodes and lungworms improved production, the additional removal of liver flukes enhanced production gains as well as reducing deaths. PMID- 1304661 TI - Losses from foot-and-mouth disease in a mixed farming area of eastern Ethiopia. PMID- 1304660 TI - Effect of palm oil meal on the colour of egg yolks. PMID- 1304662 TI - Productivity and health of camels (Camelus dromedarius) in Somalia: associations with trypanosomosis and brucellosis. AB - In Somalia, one of the world's largest dromedary populations of about 5.3 million animals are kept by nomadic pastoralists under traditional management. Interest in the development potential of camel herds in the semi-arid areas of central Somalia initiated an investigation to determine the productivity of herds, their major diseases and likely associations among these parameters. Using a systems approach, data were collected for herd production parameters, environmental factors, management and production systems, and health variables. One thousand and thirty nine camels in 33 herds were studied in the central regions of Somalia. Trypanosoma evansi prevalence ranged from 1.7% in blood-smears to 56.4% using enzyme-linked immunosorbent micro-assay (microELISA). Seroprevalence for brucellosis was determined as 1.9% by the standard agglutination test (SAT) and 0.3% by the complement fixation test (CFT). Using multiple regression, 15% of the total variation of the general fertility rate was explained by the results of the microhaematocrit centrifugation technique (MHCT) and the microELISA for T. evansi, CFT results for brucellosis, herdsize, and young stock death rate. Among herd production variables, herd size differed significantly for different management units. Young stock death rates, as well as general fertility rates varied in the ecological subzones with a marked effect in the zones labeled "Inland". Various other associations were noted among demographic, husbandry and disease variables. The importance of trypanosomosis and brucellosis to the productivity of herds and measures to control their limiting effects on production were discussed. PMID- 1304664 TI - Buffalo and Bali cattle--exploiting their reproductive behaviour and physiology. AB - Water buffalo (Bubalus bubalis) and Bali cattle (Bos sondaicus) occupy production niches in much of the developing world's agricultural systems which in the developed world are occupied by Bos indicus and Bos taurus. Both the former species are better-adapted to these environments and systems. Both depend on population survival strategies different from each other's and from those of B. indicus and B. taurus. Water buffalo rely on longevity and late sexual maturity, while Bali cattle rely on high conception rates and sacrifice of juveniles when the population is under stress. Knowledge of these different strategies will help in formulation of management strategies for maximising nett reproductive rates. This paper briefly describes each species, reviews its survival strategies and summarises the available data on the reproductive characteristics of each. PMID- 1304663 TI - Therapeutic activity of isometamidium chloride in Boran cattle against a tsetse transmitted clone of Trypanosoma congolense with a low level of drug resistance. AB - Experiments were conducted with a clone of Trypanosoma congolense, IL 3580, which exhibited a low level of resistance to isometamidium chloride. Five cattle were treated intramuscularly with isometamidium chloride at a dose rate of 0.5 mg kg-1 body weight (BW) and challenged 28 days later with 5 Glossina morsitans centralis infected with T. congolense IL 3580. All 5 cattle and 15 untreated steers challenged on the same day became parasitaemic by day 15 post-infection. Thus, at a dose of 0.5 mg kg-1 BW, the prophylactic action of isometamidium chloride did not extend to 28 days following treatment. Subsequently, the 20 steers were divided into 4 groups of 5 animals each and treated with isometamidium chloride at one of the following dose rates; 0.5 or 1.0 mg kg-1 BW intramuscularly and 0.5 or 1.0 mg kg-1 BW intravenously (Groups A, B, C and D, respectively). Group A consisted of the 5 animals that had previously been treated with isometamidium chloride. Animals relapsed in all groups except those in Group B, treated intramuscularly with isometamidium chloride at a dose of 1.0 mg kg-1 BW. Four of the 5 animals in Group A, treated intramuscularly with isometamidium chloride at a dose of 0.5 mg kg-1 BW relapsed following a mean interval of 16 days post treatment. Similarly, infections in all animals in Groups C and D, given intravenous injections of isometamidium chloride at a dose of 0.5 and 1.0 mg kg-1 BW, respectively, were not eliminated as a result of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304665 TI - A severe outbreak of orf involving the buccal cavity of goats. PMID- 1304666 TI - Multiple drug-resistant bovine trypanosomes in South Darfur Province, Sudan. PMID- 1304667 TI - Reproduction in female cattle in a communal farming area of Zimbabwe. AB - Cattle in a communal farming area of Zimbabwe were identified and examined in the late dry and mid wet season of 1985/86. Ovarian activity rates were 17.9% and 38.6% in the dry and wet season respectively. Pregnancy rates were 16.1% and 24.6% respectively. A major limitation to reproduction was the percentage of anoestrous females. There was no evidence of a seasonal calving pattern. Median body condition score was 2.0 in the dry season and 1.5 in the wet season. Adult females of body condition score 2.5 and above had ovarian activity rates of 41.9% and pregnancy rates of 41.9 per cent. Those with a body condition score below 2.5 had rates of 26.8% and 16.4% respectively. Serum progesterone levels in pregnant animals were positively related to body condition score, with some animals having progesterone levels similar to non-pregnant animals. Metabolic profiles suggested that the major limiting nutrient in both seasons was nitrogen, although other micronutrients might also be involved in low reproductive rates. PMID- 1304668 TI - Effects of an increased PO2 during recompression therapy for the treatment of experimental cerebral arterial gas embolism. AB - In this study we investigated the efficacy of an initial compression to 6 atm abs on a 53% nitrogen:47% oxygen mixture (PO2 = 2.8 atm abs) before breathing oxygen at 2.8 and 1.9 atm abs for the treatment of feline cerebral arterial gas embolism. Neurophysiologic function was determined by measuring the cortical somatosensory evoked potential (SEP) amplitude in anesthetized ventilated cats. Air was infused into the carotid artery until the SEP amplitude was reduced to less than 10% of baseline values. The animals were randomly separated into 3 groups. The first group (CONTROL) (n = 7) served as control and remained at the surface, breathing air. The second group (NITROX) (n = 10) was compressed to 6 atm abs breathing a 53:47% nitrox mixture for 30 min followed by breathing 100% oxygen at 2.8 and 1.9 atm abs. The third group (HBO) (n = 10) was compressed to 2.8 and 1.9 atm abs breathing 100% oxygen. Air infusion suppressed the SEP amplitude to the same level in all groups. The CONTROL group recovered 27.6 +/- 31.2% (mean +/- standard deviation) of the baseline SEP amplitude, whereas the NITROX group recovered 63.2 +/- 28.2%, and the HBO group recovered 66.0 +/- 19.3%. An analysis of variance with repeated measures revealed that both treatment profiles promote significant (P = 0.03) recovery of the SEP amplitude compared to no treatment. We find no additional benefit, however, by initiating treatment at 6 atm abs, even when additional oxygen is provided. PMID- 1304669 TI - Effects of hyperoxia on human endothelial cell proliferation and morphology in vitro. AB - The effects of hyperoxia on endothelial cells from human umbilical veins were studied in vitro by flow cytometric DNA analysis, cell proliferation, and morphology. Exposure of the cells to PO2 of approximately 400 and 500 mmHg (corresponding to O2 concentrations of 65 and 95%, respectively) caused, after 24 h, an increase in the proportion of S-phase cells from 18 to 33%. This was followed by a dramatic decrease of S-phase cells to about 4% after 48 h of O2 exposure. This decrease was also sustained after 72 h of O2 treatment. Concomitant with the depletion of S-phase cells was an increase from 13 to 21% in the proportion of cells in the G2M phase, indicating that cells were unable to undergo cell division after a 48-h exposure to 65 and 95% O2. Cells exposed to various PO2 levels (124, 248, 400, and 500 mmHg) showed a dose-dependent reduction in cell proliferation leading to a total inhibition of cell growth after exposure to PO2 of 400 and 500 mmHg. Cells exposed to 248 mmHg PO2 exhibited similar growth rates as the control cells during the first 3 days. Thereafter there was a 50% reduction in cell density as compared to the control cells. Light and scanning electron microscopy showed that the hyperoxic cells underwent morphologic changes characterized by cell contraction and swelling. Thus it is shown that exposure to very high PO2 tensions first stimulates the cells to enter the S phase of the cell cycle. Thereafter changes take place leading to a nearly complete reduction of cell proliferation. PMID- 1304670 TI - Physiologically and subjectively acceptable breathing resistance in divers' breathing gear. AB - To determine acceptable levels of breathing resistance in divers' gear, 6 subjects were exposed to varying levels of breathing resistance under demanding and realistic conditions. The immersed air-breathing subjects exercised in the prone position at 60% of their maximum oxygen uptake for 25 min in a hyperbaric chamber at 1.45 and 6.8 atm abs (145 and 690 kPa, 4.5 and 57 msw, 15 and 190 fsw). The breathing resistance ranged from minimal to 8-12 cmH2O (0.8-1.2 kPa).liter-1.s at flow rates of 2-3 liter/s. The higher resistance levels interfered with the respiration in terms of end-tidal PCO2 and dyspnea scores. There were considerable individual differences, and changes in one parameter were typically not paralleled by changes in the other. None of maximal voluntary ventilation, forced expiratory volume, expiratory reserve volume, vital capacities, or oxygen uptake was influenced by resistance. We set the maximum allowable end-tidal PCO2 at 60 mmHg and maximum dyspnea score at 1.0 on a scale from 0 (none) to 3 (severe). Based on these criteria we concluded that the external work of breathing should not exceed 1.5-2.0 J/liter in the ventilation range 30 to 75 liter/min BTPS. PMID- 1304671 TI - Pneumothorax as a complication of recompression therapy for cerebral arterial gas embolism. AB - The danger from pneumothorax in patients who undergo compression chamber treatment for cerebral arterial gas embolism (CAGE) following pulmonary barotrauma is frequently emphasized. Two cases of CAGE treated by recompression after submarine escape tank training (SETT) accidents are described. Both were complicated by bilateral pneumothoraces but the first case, treated on an air table, required thoracentesis in the chamber, whereas the second case, treated on an oxygen table, escaped the need for in-chamber thoracentesis despite large pneumothoraces. Review of similar Royal Navy and United States Navy SETT accidents suggests that the danger from pneumothorax during recompression treatment of CAGE victims may be overstated. Modern management on oxygen-based therapeutic recompression tables may significantly reduce the risk. Thoracentesis while under pressure should be reserved for cases developing symptoms or signs of tension pneumothorax. Treatment options for these cases are discussed and a decision algorithm is proposed. PMID- 1304672 TI - Posterior shoulder dislocation and humeral head necrosis in a recreational scuba diver with diabetes. AB - An insulin-dependent diabetic who was previously a recreational scuba diver suffered a posterior shoulder dislocation after a trivial injury and was subsequently found to have local necrosis of the humeral head. The only definite conclusion that can be reached is that this patient should not dive again. PMID- 1304673 TI - Description and evaluation of a simple method for microbiological studies on otitis externa. AB - A simple cultural method for identification of the bacteria and yeasts likely to cause external otitis in divers is described. The method employs a commercial dip slide system (Urotube) in which ear swabs are rolled onto the three agar surfaces, spread by a loop, and then incubated for a period of 18 h or more at 37 degrees C. The method was compared with traditional culture methodology on agar plates. Use of reference strains of bacteria and stored clinical isolates of bacteria and yeasts from ear infections showed stable patterns of growth for each species. Semiquantitative investigation of growth showed that there was a constant relationship between amount of growth on agar plates as compared to the dip-slide. Results were reproducible and were not affected by prolonged incubation. Directly inoculated swabs from normal ear canals and clinically infected ear canals showed identical findings by the traditional culture and Urotube methods. The Urotube method has also been evaluated in practical situations offshore with favorable experience. The Urotube method thus provides a rapid and simple way of identifying the causes of external otitis in divers in isolated areas where laboratory facilities are not readily available. This can have consequences for speed and choice of therapy in isolated environments. PMID- 1304674 TI - The Americans with Disabilities Act and the injured diver. PMID- 1304675 TI - Saturation decompression schedules based on a critical tissue supersaturation criterion. PMID- 1304677 TI - Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl. AB - The effect of Dinh lang root extract (DLRE) and (-)deprenyl on memory function and lifespan was examined in OFA-1 male mice. Treatments of either DLRE, ( )deprenyl or their combination were carried out 3 times a week starting at 12 months of age and following to the end of life. DLRE and (-)deprenyl significantly increased the memory function as well as surviving time of aged mice. The drug-treated animals showed a lower rate of loss of body weight than saline treated ones. It suggested that DLRE and (-)deprenyl did not prolong lifespan of mice by suppressing food intake. The combined treatment of DLRE and ( )deprenyl proved to be the most effective. PMID- 1304676 TI - Effects of systemic and intracerebral administration of glucose oxidase on the blood sugar level in rats. AB - Intravenous administration of 10 to 40 U/g b.w. glucose oxidase produced hypoglycaemia in a dose-dependent manner. The enzyme-induced drop of the blood sugar level was associated with significant rise in serum potassium and the concentration of free fatty acids. Intracerebral application of glucose oxidase through chronically implanted cannula into the ventromedial, lateral hypothalamus, preoptic region and amygdaloid complex of nuclei failed to change the blood sugar level, although a moderate increase of the free fatty acids and corticosterone concentrations occurred. The local application of enzyme in the locus coeruleus region led to a significant rise of the blood sugar concentration. The observations suggest the sensitivity of brainstem catecholaminergic neuronal system to hypoglycaemia. PMID- 1304678 TI - Effect of (-)-para-fluoro-deprenyl on survival and copulation in male rats. AB - Six-month old male rats were treated with 0.25 mg/kg, s.c., (-)p-fluoro-deprenyl (n = 40) or salt solution (n = 20) three times a week for 25 months. Three of the 20 saline-treated and 15 of the 40 drug-treated males survived (p = 0.05). Sexual activity of the survivors was tested at the end of the experiment. Three of the ( )p-fluoro-deprenyl-treated 31-month-old males proved to be sexually fully active, though, Wistar rats lose their ability to ejaculate by completing their second year of life. Non-copulator, 13 month old male rats were treated instead of the usually used 0.25 mg/kg dose with 0.01 mg/kg, s.c., (-)deprenyl (n = 9), (-)p fluoro-deprenyl (n = 9) and salt solution (n = 9), three times a week, for 82 weeks and mating activity was tested weekly. The lifespan of the non-copulators was very short: 102 weeks for saline (n = 9), 106 weeks for (-)deprenyl (n = 8) and 104 weeks for (-)p-fluoro-deprenyl (n = 7). Survival was lightly changed by this very small dose treatment, one (-)deprenyl-treated male and two (-)p-fluoro deprenyl-treated rats remained alive. The copulatory activity, however, was substantially improved. PMID- 1304679 TI - Conventional and prospective molecular targets in antitumour drug design. Concepts in antitumour research. AB - To introduce a rationale in a drug development program the molecular base of the pathological lesion must be carefully considered both for selecting test compounds and to apply the most appropriate assay systems. From the beginning of antitumour drug research the principal aim has always been to select chemical compounds which could selectively inhibit tumour growth. This strategy was in full harmony with the concept that tumours are build up by fast proliferating cells. Research based on this concept has resulted in the development of more than 40 cytostatic agents, which are rather diverse in their chemical properties, but all act on one of the molecular mechanisms participating in cell proliferation. However the unsatisfactory therapeutic responses which could be obtained by the cytostatic agents focused the attention on those molecular events in the tumour cells which may be more closely related to the progression of the malignant disease. PMID- 1304680 TI - Effect of cyclosporin-A treatment on microsomal enzyme activities in rat liver. AB - The effect of orally administered fixed dose cyclosporin-A (CsA) on rat liver monooxygenase activities was studied. Group I was treated for 3, group II for 7 and group III for 17 consecutive days. A time dependence in the degree of inhibition and number of microsomal enzyme activities inhibited was observed. PMID- 1304681 TI - Pharmacokinetics of radiopharmaceuticals. AB - The pharmacokinetics of various radiopharmaceuticals following i.v. administration in mice and rats has been studied and compared. Before injection the radiochemical purity (RP) of the compounds were determined by HPLC and PAGE. In all cases RP-s were higher than 90%. The biodistribution of 99mTc labelled anti CEA IgG was studied in mice bearing human colon carcinoma xenografts. Animals with different tumour weights showed different blood kinetic and tumor uptake. The pilot clinical study of the 99mTc labelled anti melanoma Fab and 111 In-DTPA labelled anti melanoma F(ab')2 showed differences in the pharmacokinetic parameters. (99mTc labelled: comp.A. 84.6%; T1/2:0.6 h, 111-In-labelled: comp.A.: 46%, T1/2 1.5 h.) The various isonitrile derivatives synthetized in our laboratory were labelled with 99mTc and the biodistribution were tested in rats. The kinetic study showed that all the three molecules have different half lives in the heart and liver (T1/2 for heart ranged 5.1-18.6 h, for liver T1/2:1.2-2.5 h). Reversed phase HPLC study of the collected bile showed the 15-100% of injected compounds are metabolized during hepatic excretion. Literature data and our recent observations confirm that the knowledge of pharmacokinetics of radiolabelled compounds both in research, development and clinical practice is of basic importance. PMID- 1304682 TI - In experimental ricin intoxication there is a detectable gastric acid secretion in the rat. AB - According to previous investigations, ricin the toxic protein of castor oil seeds (Ricinus communis, Euphorbiaceae) given in subtoxic dose, evokes a parathyroid lesion with a consecutive parathormone mobilization in the rat. The elevated parathormone level rises the plasma calcium-content resulting (among others) in endogenous gastrin mobilization. This latter increases the gastric acid secretion in significant degree. This, hitherto unknown effect of ricin directs the attention once again to the complexity of its toxic action. PMID- 1304683 TI - Breathlessness in healthy subjects at physical load. AB - The aim of the study was to ascertain the reasons which lead to discontinuance of exercise on the bicycle ergometer in healthy untrained subjects and to assess the dependence of dyspnea on breathing pattern and on ventilation. The physical load was progressively increased to the maximum in 11 volunteers at the age of 21 +/- 1 years. During exercise some cardiovascular and respiratory parameters were measured simultaneously with the degree of dyspnea. Breathlessness was rated by means of a scaling according Borg, where 0 indicates no, 10 maximal dyspnea. Dyspnea was not a reason for termination of maximal exercise, its value being 6 +/- 1.9 in men and 4.5 +/- 2.3 in women at the end of exercise. The reasons for termination of exercise were the sensations of general fatigue and pain in lower the extremities. The degree of dyspnea correlated with the minute ventilation, with the decrease of end-tidal CO2 concentration, with the duration of exercise and some other values. The grading varied among subjects. The mathematical dependence of dyspnea was summarised by two regression equations, one without suppression, the other with suppression of interindividual differences in responses. PMID- 1304684 TI - [Question of the month: Is "shaving" excision of nevus lawful?]. PMID- 1304685 TI - [Use of index in therapeutic clinical trials]. PMID- 1304686 TI - [Klinefelter's syndrome and leg ulcers: role of blood coagulation disorders]. AB - Genetically, Klinefelter's syndrome is characterized by a super-numerary chromosome X in male subjects presenting with clinical and biochemical hypoandrogenism and relative hyperoestrogenism. The association of Klinefelter's syndrome with chronic leg ulcer has given rise to numerous publications. The cause of the trophic disorders is unclear. We report two cases of this syndrome associated with chronic leg ulcers and anomalies of haemostasis. One of these two patients had platelet hyperaggregability followed by disorders of fibrinolysis, while the other had disorders of fibrinolysis. We reviewed the literature concerning the various aetiopathogenic hypotheses put forward to explain the cause of these leg ulcers, as well as their interactions and relationship with the hormonal anomalies. The position occupied by disorders of haemostasis is particularly developed. PMID- 1304687 TI - [Immunohistochemistry of nodular vasculitis. A possible role of delayed cellular hypersensitivity]. AB - The physiopathogenesis of nodular vasculitis is still unknown: there is probably an initial Arthus' phenomenon responsible for the lesions of the deep vessels, but the frequent recurrences and the long time duration of the hypodermic nodules are still not understood. Dendritic protein S100 positive cells had previously been observed within hypodermal granulomas. The purpose of this study was to confirm these observations in a large group of nodular vasculitis, and to compare the expression of S100 protein in other vascular diseases and in pure panniculitis. Immunohistochemical staining for S100 protein was performed on paraffine-embedded samples: 45 cases of nodular vasculitis, 21 of panniculitis, 10 of superficial leucocytoclastic vasculitis, 10 of periarteritis nodosa, and 10 of erythema nodosum were analyzed by means of optic microscopy. Numerous dendritic S100 protein positive cells were found within hypodermal granulomas in most of the cases of nodular vasculitis, but these cells were absent in the 3 cases of initial deep leucocytoclastic vasculitis lesions of nodular vasculitis. The mean percentage of these cells was 4.5 p. 100 in the hypodermal inflammatory areas; they were observed mainly around vascular lesions. Hypodermal dendritic cells were absent or less numerous in all other cases, and a high number of such cells seems to be observed only in nodular vasculitis. Because of their dendritic morphology, and the high expression of S100 protein, these cells could be interdigitated cells, which are known to present antigens to T-lymphocytes. They could play an important role in generating the chronicity of nodular vasculitis, by a mechanism of delayed cell-mediated hypersensitivity, after the initial lesions caused by immune complexes. PMID- 1304688 TI - [Epidermal cyst and osteolysis of the cranial vault]. AB - In a 40-year old man undergoing, under local anaesthesia, excision of an epidermal cyst located in the frontal region, at the border of the scalp, the operator had difficulties in removing the deep part of the cyst and perceived an underlying bone depression. The depression was caused by a 2 x 1.3 cm wide lacuna in the calvarium, which was subsequently treated by neurosurgeons. Histology showed only fragments of a simple epidermal cyst wall and no evidence of dermoid cyst. The causes of osteolysis associated with congenital or acquired skin lesions are reviewed. In this case, the old age and volume of the cyst may explain the osteolysis by mechanical compression. This case is exceptional since we were unable to find other examples in the literature, apart from dermoid and trichilemmal cysts. PMID- 1304689 TI - [Mibelli's porokeratosis after bone marrow transplantation]. AB - A 24-year old male patient developed, on both legs, lesions typical of Mibelli's porokeratosis 22 months after bone marrow transplantation, under treatment with cyclosporin A. He denied any family history. Mibelli's porokeratosis seldom develops after an immunosuppressive treatment, and to our knowledge it has exceptionally been described after bone marrow transplantation. A possible complication of Mibelli's porokeratosis is the development of Bowen's disease, basal or squamous cell carcinomas. Immunosuppressive treatment might facilitate the degeneration. For this reason, these subjects should be periodically and carefully examined. PMID- 1304690 TI - [Association of sarcoidosis and Waldenstrom's macroglobulinemia]. AB - Sarcoidosis is seldom associated with Waldenstrom's macroglobulinaemia. We report the case of a 58-year old woman, 7 years after cutaneous and pulmonary sarcoidosis had begun, developed Waldenstrom's macroglobulinaemia. Chlorambucil was effective on both diseases. The possibility of reactive sarcoidotic granulomas in neoplastic diseases may cast doubts on the reality of the sarcoidosis-malignant haemopathy association. However, most authors consider that such associations are not fortuitous and can be explained by the immunological abnormalities observed in patients with sarcoidosis. PMID- 1304691 TI - [Cutaneous pigmentation induced by minocycline: ultrastructural analysis and X ray microanalysis]. AB - The authors report a case of cutaneous pigmentation induced by minocycline. The patient (aged 59) presented with a bluish-grey pigmentation on her face, legs and nails. She had been receiving minocycline for 8 years for asthma. The cumulative dose was 400 g. Skin biopsy specimens from the pigmented areas were examined by light and electron microscopy. Light microscopy displayed hyperpigmentation with Fontana's stain in the dermis, macrophages and basal layer of the epidermis. Electron microscopy showed an increase in melanosomes within the basal keratinocytes, and dense granules in macrophages of the dermis. An X-ray microanalysis of the electron-dense granules showed the presence of larger quantities of iron and smaller quantities of sulphur and calcium. The different types of pigmentation are reviewed. Several pigments are thought to be responsible for the pigmentation but the underlying mechanism remains unclear. PMID- 1304692 TI - [Carcinoma of the tongue in xeroderma pigmentosum]. AB - Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by a defect in the repair of DNA damage induced by ultraviolet rays. The cutaneous tumours are frequent and occur at an early age, but neoplasias of the mucosae are seldom observed. Among the mucosae, the lipids and the conjunctiva clearly predominate. Tumours of the buccal cavity are much less frequent, and this is why we report a case of epidermoid carcinoma of the tip of the tongue in a Moroccan boy. Only 25 cases of intrabuccal tumour have been reported in patients with XP, and 22 were epidermoid carcinomas of the tip of the tongue. These carcinomas may be preceded by precancerous lesions such as leucoplasia. The early occurrence and elective location at the tip of the tongue clearly differentiate lingual carcinomas associated with XP from their homologues in adults. The aggressiveness of these lesions is difficult to determine due to a usually short follow-up and to the lack of details in reports. Treatment is surgical and non-specific. Concerning epidemiology, the predominance of African and Near-Eastern patients among those suffering from lingual carcinoma is striking. Moreover, when the complementation group is known it is always group C; our patients presented with characteristics of this group. Some authors believe that the lingual tumours are due to ultraviolet light (overexposure in case of natural pigmentation, with exposure of the tip of the tongue) and to certain toxic substances in food.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304693 TI - [Contact fentichlor photoallergy from soap for handwashing]. PMID- 1304694 TI - [Comment on the case for diagnosis: scleroatrophic lichen of the prepuce]. PMID- 1304695 TI - [Comment on the case for diagnosis: scleroatrophic lichen of the prepuce]. PMID- 1304696 TI - [A case for diagnosis: lichen planus in a case of genito-gingival syndrome]. PMID- 1304697 TI - [Skin diseases of the vulva in children]. PMID- 1304699 TI - An outbreak of Plasmodium vivax malaria in Trinidad, W.I. AB - An outbreak of Plasmodium vivax malaria occurred in Trinidad some 25 years after a successful eradication programme. The 'index case' was infected while visiting Perdaneles, Venezuela, and was responsible for the renewal of malaria transmission by indigenous Anopheles aquasalis mosquitoes in Icacos, Trinidad, W.I. Nine cases (four females and five males) of P. vivax malaria were locally transmitted in Icacos. Most of the cases (70%) were in the 15-24 or 25-44 year age groups. In Granville/Chatham, another, unrelated case of locally transmitted P. vivax malaria was discovered through active surveillance. The intervention measures adopted, which successfully eradicated P. vivax malaria from Trinidad, are described. The need to maintain malaria surveillance is emphasized. PMID- 1304698 TI - Mefloquine-sulphadoxine-pyrimethamine (Fansimef, Roche) in the prophylaxis of Plasmodium falciparum malaria: a double-blind, comparative, placebo-controlled study. AB - From July 1987 to June 1988 a randomized, double-blind, comparative placebo controlled field trial was conducted in a group of villages near Ibadan, Nigeria. The aim of the study was to assess the suppressive tolerability and efficacy of four antimalarials (Fansimef, Lariam, Fansidar, chloroquine) given for 24 weeks. Fansimef and Lariam were given with loading and maintenance doses, Fansidar and chloroquine as one tablet per week for 24 weeks. Of 567 enrolled subjects, 114 (20%) had parasitaemia on entry. Eight episodes of symptomatic falciparum malaria occurred during the trial, seven in the placebo group, and one in the Fansimef group. Compared with placebo, parasitaemia was effectively suppressed by all four drug regimens. Adverse event data were not significantly different between groups: six adverse events per 114 participants in the Fansimef group, six/113 in the mefloquine group, five/111 in the Fansidar group, 17/115 in the chloroquine group and eight/114 in the placebo group. Safety of Fansimef for 24 weeks in endemic areas was comparable for standard antimalarials in this trial and provides support for the use of this drug for the treatment of resistant malaria in indigenous African populations. PMID- 1304700 TI - High seasonal malaria transmission rates in the intermediate rainfall zone of Sri Lanka. AB - Malaria transmission was studied at Nikawehera, a long-established farming village, located in the intermediate rainfall zone of Sri Lanka. Observations were made over a 12-month period (October-September) that included the main rainy season which occurred during the north-east monsoon in November-January. Anolpheles culicifacies, the recognized vector of malaria in Sri Lanka, was the predominant anopheline mosquito collected by human night baiting at Nikawehera. High entomological inoculation rates with An. culcifacies (0.12/hour for Plasmodium vivax) were observed during the height of the transmission season which occurs during, and immediately after, the north-east monsoon. Anolpheles subpictus was identified as a possible additional vector at Nikawehera. Anopheles annularis, a major vector at Weheragala, a site in a new irrigation development (the Mahaweli Scheme) located 70 km away in the dry zone, was not collected by human baiting at Nikawehera. Clinical, entomological and parasitological data suggest that malaria is hyperendemic at Nikawehera, with high seasonal transmission rates. PMID- 1304701 TI - Altered plasma lipid pattern in falciparum malaria. AB - Plasma levels of HDL, LDL, total cholesterol and triglycerides were measured in 60 patients with falciparum malaria (37 severe cases and 23 mild) and in 83 healthy individuals, to study malaria-induced changes in plasma lipids. Triglyceride levels were lower in the patients than in the controls but the difference was significant only for those with severe malaria (P < 0.001). In contrast, the levels of all the other plasma lipids were significantly higher (P < 0.001) in those with severe malaria than in those with mild malaria, and in the mild malaria cases compared with the controls. Initially LDL cholesterol was estimated by the Friedwald formula, but this gave negative values in a few cases of severe malaria. Plasma lipoproteins were therefore also measured by nephelometry; the estimated levels of S particles, corresponding to LDL, were then found to be lower in all malaria cases than in the controls (P < 0.001) but never negative. Interestingly, levels of L particles in the patients with severe malaria were significantly elevated compared with the other patients and controls (P < 0.001), indicating impaired metabolism of chylomicrons. Plasma albumin, considered a negative acute phase protein (i.e. its level decreases as a consequence of the acute phase response), was reduced significantly and was directly correlated to HDL cholesterol levels (r = 0.715 and r = 0.895, respectively) in both mild and severe malaria. Follow-up of 22 of the severe malaria cases three weeks after treatment indicated that, while triglycerides had returned to similar levels to those in the controls, total cholesterol levels were still elevated and could give misleading results if lipid profiles were used, immediately after malaria infection, to assess an individual's risk of developing atherosclerosis. PMID- 1304702 TI - Didelphis marsupialis: a primary reservoir of Trypanosoma cruzi in urban areas of Caracas, Venezuela. AB - Direct blood examination and xenodiagnosis of 45 sylvatic, peridomestic or domestic mammals from the Caracas valley, Venezuela, revealed trypanosome infection in six of the 24 opossums, Didelphis marsupialis, collected in urban areas. Isolates were successfully made of trypanosomes from four of the opossums, using the parasites which developed in Rhodnius prolixus fed on the infected opossums to infect NMRI mice. The prepatent period, course of parasitaemia, morphology of bloodstream trypomastigotes, tissue tropism of parasites in the opossums and/or mice, host mortality, morphology of parasites in the bugs, and infectivity to mice of parasites in the faeces of infected bugs, were all characteristic of Trypanosoma (Schizotrypanum) cruzi. In mice, the parasites showed marked myotropism; the heart, skeletal muscle and the smooth muscle of the urinary bladder, penis, prostate, seminal vesicle, lung, stomach, jejunum and colon were frequently invaded, and pseudocyts were also occasionally found in the liver, brain and pancreas. The significance of the invasion of the genito-urinary structures as a possible alternative parasite transmission route is discussed. The possible role of D. marsupialis, as a primary reservoir of T. cruzi, in the establishment of foci of Chagas' disease in Caracas and other Latin American cities, is emphasized. PMID- 1304704 TI - Analysis of the in vitro lymphoproliferative responses and antibody levels to the arc-5 antigen in patients with cystic hydatid disease. AB - Using a commercially-available, purified, arc-5 antigen, we examined the in vitro proliferative responses of peripheral blood mononuclear cells from hydatid patients and from healthy controls. Antibody levels of different immunoglobulin classes were also measured against the same antigen, in sera of both groups. Our findings indicate that lymphocytes from healthy controls do not proliferate to the arc-5 antigen, whereas lymphocytes from the majority of patients do. The negative or weak responses observed among a few patients were not due either to increased release of prostaglandins in culture or to a lack of responsiveness to Interleukin-2. Antibodies of all three classes, G, M and A, measured by an ELISA, were elevated in sera of patients when compared with controls. However, only levels of specific IgG antibodies gave an excellent discrimination of the disease state and these were of diagnostic value. No direct or inverse correlations between lymphoproliferative responses and antibody levels were observed in either group, although a few patients with relatively low antibody titres demonstrated very high proliferative responses. The possible use of the proliferative assay as an adjunct to serology in the diagnosis of hydatid disease is indicated. PMID- 1304703 TI - Decreased sensitivity to meglumine antimoniate (Glucantime) of Leishmania infantum isolated from dogs after several courses of drug treatment. AB - Although unresponsiveness to antimonial drugs in human leishmaniasis appears to be increasing, resistance to antimony in Leishmania is not well documented. Treatment of leishmaniasis in dogs, the domestic reservoir of L. infantum, with meglumine antimoniate (Glucantime) is a common practice in many Mediterranean countries. The dogs, however, remain highly infective to the phlebotomine vectors, even after several courses of treatment. A study was therefore carried out to test the comparative susceptibility to meglumine antimoniate of L. infantum stocks isolated from four naturally-infected dogs, before (BT) and after treatment (AT) with three to six courses of the drug, and used to infect Balb/c mice. Significant differences in suppression between the BT and AT stocks were observed in the infected mice when they were given the drug at a rate of 0.01-10 mg kg-1 day-1 for five days. Each AT stock was between eight and 41 times more resistant to meglumine antimoniate than the BT stock from the same dog, in terms of the ratios of the AT ED50 values to the corresponding BT values, which were calculated as indices of resistance. This result underlines the futility and danger of repeated antimonial treatments of dogs with signs of leishmaniasis, as these may produce a permanent reservoir of parasites unsusceptible to the drugs in human clinical use. PMID- 1304705 TI - Experimental schistosomiasis mansoni: modulation of granulomas by inhibition of collagen cross-link formation. Preliminary report. AB - beta-Aminopropionitrile (BAPN) is an inhibitor of the lysyl oxidase required for cross-link formation in collagen maturation. The efficacy of BAPN, alone or in association with the anti-schistosomal drug, praziquantel (PZQ), was primarily assessed by measuring the reduction in liver and intestinal egg loads in murine schistosomiasis mansoni. Depending on the treatment group (PZQ, BAPN, BAPN + PZQ), organ-specific effects were observed using microscope image analysis. Most notable was the relatively small size of granulomas in the livers of BAPN-treated mice, which contrasted with the relatively large size and irregular shape of the granulomas in the intestinal tissues of these mice. Mice treated with the combination of BAPN and PZQ had decreased liver and spleen weights, and a significant reduction in the number of eggs trapped in both the liver (86%) and the intestine (99.1%), compared with untreated mice and those given PZQ alone. The lowest number of living eggs/g of tissue in both the liver and intestine was recorded in the combined BAPN + PZQ-treated group. These results suggest that the concurren treatment of infected mice with PZQ and BAPN enhances the release of eggs trapped in the intestine and also results in a significant reduction of liver egg load. The mechanism by which BAPN reduces the number of liver granulomas in PZQ-treated mice is currently being investigated. PMID- 1304706 TI - Human onchocerciasis in the lower Jos Plateau, central Nigeria: the prevalence, geographical distribution and epidemiology in Akwanga and Lafia local government areas. AB - An investigation of human infection with Onchocerca volvulus and the resulting clinical disease was carried out for the Nigerian National Onchocerciasis Control Programme between July and August 1989 [corrected]. The survey covered 10.6% of the rural population in 41 savanna villages of central Nigeria. Of the 8451 self selected individuals examined, 900 (10.6%) had skin microfilariae (Mf). There were differences between villages in both endemicity and intensity of infection, but in general the number of both Mf carriers and cases of clinical onchocerciasis increased with age. The disease in the Mf carriers showed as blindness (0.8%), onchocercal nodules (0.6%), leopard skin (1.6%) and pruritus (2.8%). Of 35 persons with lymphatic complications, 19 had hanging groin, 10 had elephantiasis and six had hydrocoele. Onchocerciasis was mesoendemic in the rocky northern escarpments, and became hypoendemic and sporadic in the southern uplands of sedimentary geological origin. PMID- 1304707 TI - Preliminary observations on the distribution of ivermectin in Nigeria for control of river blindness. AB - A total of 118,925 individuals in four Nigerian states was treated for onchocerciasis between February and December, 1991, using centralized and house to-house distribution of ivermectin. Pre-treatment prevalences of the disease ranged between 28% and 90%. Only 0.7% of those treated reported adverse reactions within three days of treatment: 230 individuals (0.19%) had headache, 210 (0.17%) general body pains, 150 (0.12%) pruritus, 120 (0.10%) oedema, 80 (0.06%) fever, 20 (0.02%) dizziness, 15 (0.01%) vomiting, 10 (0.01%) diarrhoea, and 25 individuals (0.02%) noticed that they passed intestinal worms. Treatment in the endemic communities continues. The results show that mass treatment of onchocerciasis with ivermectin is quite safe and the drug's acceptability increases its potential as the drug of choice for control of onchocerciasis in Nigeria. PMID- 1304708 TI - The ultrastructure of the abdominal trumpet gland and antennal ascoid and papilla of Chinius junlianensis Leng, 1987 (Diptera: Psychodidae). AB - When viewed with a light microscope, each trumpet gland of Chinius junlianensis appears as 15-20 small trumpet-shaped structures with their narrower proximal ends clustered together on the surface of a tergite. By scanning electron microscopy (SEM), however, the glands appear to be abdominal exosecreting organs with honeycomb-like openings at the inter-tergal junctions 3/4 and 4/5. Although the other ascoids of C. junlianensis are round in cross-section, each of those distal to antennal segment 8 is roughly triangular, with three ridges and three concave surfaces, and has a large oval depression at its base. The basal ridge has three to five rows of denticulations. The antennal papilla is oval, with a comb-like fence of four to five thin pointed processes on each side and a stout central spine. PMID- 1304709 TI - Predation of Biomphalaria and non-target molluscs by the crayfish Procambarus clarkii: implications for the biological control of schistosomiasis. AB - The North American crayfish Procambarus clarkii was examined under laboratory conditions for its ability to prey on Biomphalaria pfeifferi and B. glabrata, molluscan intermediate hosts of human schistosomiasis, and other, non-target gastropod species. Both male and female adult crayfish significantly reduced survival of neonate snails, even though alternative animal and plant foods were both available. In subsequent experiments, no differences in snail consumption were detected, for either adult or juvenile crayfish, in the presence or absence of a plant food alternative. Both adult and juvenile crayfish were able to consume small (2.5 mm) and large (17.5 mm) B. glabrata, suggesting that no size refuge from predation exists. Both adult and juvenile crayfish consumed Biomphalaria egg masses, although this consumption was significantly greater for juveniles. Procambarus clarkii adults were unable to consume substantial numbers of the relatively thick-shelled prosobranch snails Pila ovata and Lanistes carinatus. Crayfish did consume a third prosobranch, Melanoides tuberculata, and the pulmonate snail Physa acuta, but at a lower rate relative to consumption of Biomphalaria. Physa acuta, itself of North American origin, responded to the presence of crayfish by rapidly leaving the water and thereby avoided predation. Implications of these results for the biological control of schistosome transmitting snails in East Africa are discussed. PMID- 1304710 TI - Polyparasitism on the Kenya coast. 1. Prevalence, and association between parasitic infections. AB - A partially-stratified sample survey of people living in the catchment area of Kilifi General Hospital, Coast Province, Kenya, identified 19 species of parasites in blood and intestines. Age-prevalence curves of the common infections were of two distinct types, possibly reflecting the host's ability to mount a partially effective immune response. Although statistically-significant associations between pairs of infections were clearly demonstrable, these were almost wholly explained by environmental heterogeneity and epidemiological coincidence. There was no evidence of positive or negative influence of one infection on another. PMID- 1304711 TI - Virulence of Trypanosoma simiae in pigs infected by Glossina brevipalpis, G. pallidipes or G. morsitans centralis. PMID- 1304712 TI - Diabetes and heat shock protein. PMID- 1304713 TI - Long thoracic neuropathy from athletic activity. AB - Four cases of long thoracic mononeuropathy associated with sports participation are presented. Each patient developed shoulder pain or dysfunction after an acute event or vigorous activity, and demonstrated scapular winging consistent with serratus anterior weakness. The diagnosis was confirmed with electromyography in each case. It is suggested that the athletic activity caused a stretch injury to the long thoracic nerve. Conservative management, consisting of range of motion exercises for the shoulder and strengthening of the serratus anterior muscle, resulted in a favorable outcome in all patients. PMID- 1304714 TI - The characteristics of the Ricketts maxillary canine retractor. AB - The characteristics of the Ricketts maxillary canine retraction spring (Ricketts, 1974) have been derived using the complementary (strain) energy method. The theoretical predictions of the analysis have been confirmed by experiments on large planar models in a jig fitted with strain gauges capable of measuring the forces and couples developed when the springs were activated in a way simulating clinical use. The verified analysis was used to compare the horizontal stiffness and anti-tilt couple to retraction force ratios of the Ricketts with other simpler retraction components. The behaviour of the Ricketts mandibular sectional, as predicted by the analysis was also examined. PMID- 1304715 TI - Rotator cuff disease: current trends in orthopedic management. AB - Rotator cuff disease is a clinical entity that is frequently encountered in the typical primary care office. Of particular importance to the chiropractic physician is the close proximity of the shoulder joint to the cervical spine. Due to the relatively high level of morbidity in the population, rotator cuff disease should be looked at carefully on both the physical and advanced diagnostic level. Several factors contributing to rotator cuff pathology include subacromial impingement, the relative microvascular pattern of the cuff mechanism and prior trauma. The natural history of attrition and aging also play a role in rotator cuff disease. Advanced disease is successfully diagnosed through the efficient utilization and proper sequencing of advanced orthopedic imaging studies. PMID- 1304716 TI - Transnasal stereotactic biopsy of a clivus tumor. Technical note. AB - Computerized tomography-guided transnasal stereotactic tissue diagnosis of a lytic lesion in the clivus was performed successfully using the Cosman-Roberts Wells frame, thus avoiding a major craniotomy. The authors recommend stereotaxis as the preferred technique for biopsy in this region. PMID- 1304717 TI - Physician-payment reform--unfinished business. PMID- 1304718 TI - Risk of breast cancer in ataxia-telangiectasia. PMID- 1304719 TI - Risk of breast cancer in ataxia-telangiectasia. PMID- 1304720 TI - Death and reductionism: a reply to John F Catherwood. AB - This reply to John F Catherwood's criticism of brain-related criteria for death argues that brainstem criteria are neither reductionist nor do they presuppose a materialist theory of mind. Furthermore, it is argued that brain-related criteria are compatible with the majority of religious views concerning death. PMID- 1304722 TI - Toxoplasma gondii pneumonitis in patients infected with the human immunodeficiency virus. AB - Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms. PMID- 1304721 TI - An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. AB - BACKGROUND: Since 1990 several clusters of multidrug-resistant tuberculosis have been identified among hospitalized patients with the acquired immunodeficiency syndrome (AIDS). We investigated one such cluster in a voluntary hospital in New York. METHODS: We compared exposures among 18 patients with AIDS in whom tuberculosis resistant to isoniazid and streptomycin was diagnosed from January 1989 through April 1990 (the case patients) with exposures among 30 control patients who had AIDS and tuberculosis susceptible to isoniazid, streptomycin, or both. We also compared exposures among the 14 case patients hospitalized during the six months before the diagnosis of tuberculosis (the exposure period) with those among 44 control patients with AIDS matched for duration of hospitalization. Mycobacterium tuberculosis isolates were typed with analysis of restriction-fragment-length polymorphism (RFLP). RESULTS: Case patients with drug resistant tuberculosis were significantly more likely than controls with drug susceptible tuberculosis to have been hospitalized during their exposure periods (14 of 18 vs. 10 of 30) (odds ratio, 7.0; 95 percent confidence interval, 1.6 to 36; P = 0.006). Case patients hospitalized during their exposure periods were significantly more likely to have been hospitalized on the same ward as a patient with infectious drug-resistant tuberculosis than were either controls with drug susceptible tuberculosis hospitalized during their exposure periods or controls matched for duration of hospitalization (13 of 14 vs. 2 of 10 and 23 of 44) (odds ratio, 52; 95 percent confidence interval, 3.1 to 2474; P less than 0.001; and odds ratio, infinity; 95 percent confidence interval, 2.4 to infinity; P = 0.005, respectively). Among those hospitalized on the same ward, the rooms of case patients were closer to that of the nearest patient with infectious tuberculosis than were the rooms of controls matched for duration of hospitalization. M. tuberculosis isolates from 15 of 16 case patients had identical patterns on RFLP analysis. Of 16 patients' rooms tested with air-flow studies, only 1 had the recommended negative-pressure ventilation. CONCLUSIONS: Multidrug-resistant tuberculosis is readily transmitted among hospitalized patients with AIDS. Physicians must be alert to this danger and must enforce adherence to the measures recommended to prevent nosocomial transmission of tuberculosis. PMID- 1304723 TI - Grappling with the enigma of violence. An educational approach. PMID- 1304724 TI - A retreat from SI units. PMID- 1304725 TI - Asymptomatic HIV infection does not cause EEG abnormalities: results from the Multicenter AIDS Cohort Study (MACS) AB - We conducted EEG testing in 200 asymptomatic homosexual men, half of whom were HIV seropositive. We chose to include half of the subjects because they were rated as impaired on a neuropsychological screening test. We used both traditional visual EEG interpretation and quantitative EEG analysis. Abnormal EEGs and borderline degrees of EEG slowing occurred in 32% of these men. These EEG changes were not related to HIV serostatus. EEG changes did correlate with the impaired neuropsychological test performance. Clinicians faced with abnormal EEG results or borderline EEG slowing in an asymptomatic HIV-seropositive patient should not attribute the EEG change to effects of the serostatus itself but should look for other causes. PMID- 1304726 TI - Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers. AB - Unstimulated leukocytes spend extended periods circulating in the blood, punctuated by migration through lymphoid areas and peripheral tissues. During transit, strong cell-cell interactions control immune surveillance and specialized effector functions. The structures and mechanisms that allow this flexible adhesion and migration behavior are the subject of this review. PMID- 1304727 TI - Prolongation of tetracaine spinal anesthesia by oral clonidine. AB - The effects of oral clonidine on the duration of isobaric tetracaine spinal anesthesia were studied in 30 patients undergoing urologic procedures. All patients received 15 mg of tetracaine intrathecally in isobaric saline solution. Group 1 (n = 10) received 0.25 mg of oral triazolam; group 2 (n = 10) received 0.15 mg of oral clonidine; and group 3 (n = 10) received 0.25 mg of oral triazolam and 0.75 mg of intrathecal phenylephrine. In group 1, the times for two and four-segment regression of the level of analgesia to pin-prick were 80 +/- 17 and 123 +/- 22 min, respectively (mean +/- SD). The corresponding values of those measurements were 170 +/- 27 and 273 +/- 48 min in group 2 and 175 +/- 34 and 273 +/- 68 min in group 3. All the regression times in groups 2 and 3 were significantly longer than those in group 1. Regression times were not different between groups 2 and 3. The authors conclude that prolongation of tetracaine sensory analgesia may be produced by premedication with 0.15 mg of oral clonidine. The prolongation is similar to that produced by intrathecal phenylephrine. PMID- 1304729 TI - Tuberculous meningitis in patients infected with the human immunodeficiency virus. PMID- 1304728 TI - HIV prevention and the two faces of partner notification. AB - In the cases of medical patients with sexually transmitted diseases (particularly those with the human immunodeficiency virus), two distinct approaches exist to notifying sexual and/or needle-sharing partners of possible risk. Each approach has its own history (including unique practical problems of implementation) and provokes its own ethical dilemmas. The first approach--the moral "duty to warn"- arose out of clinical situations in which a physician knew the identity of a person deemed to be at risk. The second approach--that of contact tracing- emerged from sexually transmitted disease control programs in which the clinician typically did not know the identity of those who might have been exposed. Confusion between the two approaches has led many to mistake processes that are fundamentally voluntary as mandatory and those that respect confidentiality as invasive of privacy. In the context of the AIDS epidemic and the vicissitudes of the two approaches, we describe the complex problems of partner notification and underscore the ethical and political contexts within which policy decisions have been made. PMID- 1304730 TI - Multidrug-resistant tuberculosis. PMID- 1304731 TI - The unfinished business of physician-payment reform. PMID- 1304732 TI - Proper prescribing prevents potential problems. PMID- 1304733 TI - Is hearing assessed after bacterial meningitis? AB - A questionnaire was sent to 686 paediatricians in the UK to discover whether or not they referred children for hearing assessment after bacterial meningitis and if not, why not; 90% replied. Of these, 10% did not refer all children. The reasons given were based on misunderstandings of the aetiology and not on a lack of provision. PMID- 1304734 TI - Optimal technique for electrical cardioversion of atrial fibrillation. PMID- 1304735 TI - Recent trends in the prevalence and severity of childhood asthma. AB - OBJECTIVE: To examine changes in the prevalence and distribution of childhood asthma and its relationship with various measures of children's health and functioning between 1981 and 1988. It was hypothesized that there would be an increase in the prevalence of asthma, especially among black children, and that available measures would suggest a deterioration in the health and functioning of children with asthma over this period. DESIGN: Analyses of data from the Child Health Supplements to the National Health Interview Survey. SETTING AND SAMPLE: Nationally representative random sample of 15,224 children aged 0 to 17 years in 1981 and 17,110 in 1988. MAIN OUTCOME MEASURES: Changes in (1) the prevalence and distribution of asthma, and (2) among children with asthma, the percentage of children hospitalized, days spent in bed, school days lost in the year prior to survey, and parent ratings and reports of children's overall health status and behavior problems. RESULTS: The estimated prevalence of childhood asthma increased from 3.1% in 1981 to 4.3% in 1988 (P < .0001), with similar increases for children, adolescents, and both sexes. Increases occurred among white children (2.7% to 4.1%; P < .0001) but not black children (5.3% vs 5.1%; not significant). Among those with asthma in 1988 compared with 1981, there was better overall health status (11% vs 24% fair/poor; P < .0001) and fewer with 30 or more days spent in bed in the last year (3.9% vs 7.2%; P < .04). We also observed trends toward a lower rate of hospitalization in the last year (10% vs 14%; P = .07), fewer school days missed (2% vs 6% with > 30 days; P = .08), and a lower rate of extreme behavior problem scores (13% vs 18%; P = .09) in 1988 compared with 1981. Reductions were similar among both black and white children. CONCLUSIONS: These results indicate that the estimated prevalence of asthma among children in the United States increased by almost 40%, and that although the increase occurred exclusively among white children, the prevalence of asthma still remains higher in black children than in white children. There was no support for increasing asthma severity and functional impact among either black or white children with asthma in 1988 compared with 1981. These findings provide no evidence to support the beliefs that asthma prevalence is increasing largely among black children or that the severity of asthma among most children in the United States is increasing. PMID- 1304736 TI - Tobacco dependence and the nicotine patch. Clinical guidelines for effective use. AB - OBJECTIVE: A comprehensive review of transdermal nicotine treatment for tobacco dependence, with recommendations derived from the research literature. DATA SOURCES: English-language clinical trials. STUDY SELECTION: Clinical trials using placebo-controlled, double-blind methodology (11 studies) with at least 6 months of follow-up after treatment (eight studies) and biochemical verification of smoking status. DATA SYNTHESIS: Nicotine patches produce end-of-treatment smoking cessation rates that range from 18% to 77%; these rates are about twice those of placebo-treated subjects. Nicotine patches produced 6-month abstinence rates of 22% to 42%, while placebo patches produced quit rates of 5% to 28%. Nicotine patches appear to reduce some, but not all, nicotine withdrawal symptoms. For instance, while the patch reduces craving for cigarettes and negative moods, it does not appear to reduce hunger or weight gain. The clinical trials literature suggests that proper adjuvant smoking cessation counseling is crucial in determining successful long-term outcome with the nicotine patch, and suggests that 6 to 8 weeks of patch therapy may be an adequate duration for most patients. CONCLUSIONS: Nicotine patches are an effective aid to tobacco dependence treatment. However, success rates vary greatly across research studies and may be influenced highly by the nature and intensity of adjuvant smoking cessation counseling. More research is needed to identify optimal duration, dosage, and individualization of patch therapy. The impact of nicotine patches (more than 5 million users with $1 billion in sales for 1992) also raises important ethical and public health issues. PMID- 1304737 TI - Physician supply policies and health reform. PMID- 1304738 TI - Age and the cardiovascular system. PMID- 1304739 TI - General practice in the UK. PMID- 1304740 TI - Cytokine inter-relationships and their association with disease activity in arthritis. AB - In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL 2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis. PMID- 1304741 TI - Quality of life measures in health care. III: Resource allocation. PMID- 1304742 TI - Managing pediatric asthma in North Carolina. PMID- 1304743 TI - The patient's charter and the triage nurse. PMID- 1304745 TI - A national standard for entry into general practice. PMID- 1304744 TI - Risks to surgeons and patients from HIV and hepatitis: guidelines on precautions and management of exposure to blood or body fluids. Joint Working Party of the Hospital Infection Society and the Surgical Infection Study Group. PMID- 1304746 TI - Direct puncture venography. PMID- 1304747 TI - A piscatorial epistle. PMID- 1304748 TI - [Studies on perpendicular distribution of rare and endangered medicinal plants in Guizhou Province]. PMID- 1304749 TI - [Pollen morphology of medicinal flowers. II. The multiple of close relative origin type]. PMID- 1304750 TI - [Effects of plant hormone on germination of Bupleurum falcatum L. seeds]. AB - The germinant rate of Bupleurum falcatum can be raised by soaking the seeds in BA or GA3 solution. The effect of BA is better than that of GA3. BA and GA3 cannot be used together, otherwise the effect on germination will be decreased or checked. BA or GA3 should be used before the natural sowing time, for after this time they will be useless or even harmful. PMID- 1304751 TI - [Pharmacological and clinical studies on the processed products of radix Polygoni multiflori]. AB - The root of Polygonum multiflorum and its 2 processed products were compared by immune pharmacology and clinical observation on the aged high-fat-blood case. The results have shown that the product processed under new procedures is better than that under traditional procedures, thus providing scientific basis for spreading the application of the new one. PMID- 1304752 TI - [Preliminary studies on arsenic content in cishi]. AB - The results have revealed that arsenic content in pig cishi is about 11 times that in the calcinated samples. Therefore the toxic effect of cishi is eliminated or reduced after it is calcinated. PMID- 1304753 TI - [Preparation and isolation of chitin and chitosan from Kronopolites svenhedini (Verhoeff)]. AB - Chitin was isolated from Kronopolites svenhedini and deacetylated to produce the derivative chitosan. The yield for chitin was 9%, and chitosan yield 57.4% and 77.5% respectively. After purification, their structures have been determined by spectroscopic methods. PMID- 1304755 TI - [Chemical constituents of Cynanchum thesioides K. Schum]. PMID- 1304754 TI - [Chemical constituents of Drynaria propinqua (Wall) J. Sm]. AB - Four compounds isolated from the rhizomes of Drynaria propinqua collected in Sichuan have been identified. One of them was a new natural product, namely propinqualin, whose structure was established as (-)-epiafzelechin-3-O-beta-D allopyranoside. The other three were 4-O-beta-D-glucopyranosyl caffeic acid, beta sitosterol-3-O-beta-D-glucopyranoside and sucrose. PMID- 1304756 TI - [Chemical studies on essential oils from 6 Artemisia species]. AB - The constituents of the essential oils obtained from the leaves of Artemisia argyi, A. argyi cv.qiai, A. lavandulaefolia, A. mongolica, A. princeps and A. argyi var. gracilis were analysed by GC-MS. 96 compounds including alpha-thujene, 1,8-cineole, camphor and artemisia alcohol, etc. were identified. Their percentages in the oils were given. PMID- 1304757 TI - [Effects of neutral oil of Ligusticum sinense Oliv. on anoxia]. AB - The neutral oil at 2.5 and 5.0g/kg P.O. can significantly decrease the oxygen consumption and prolong survival time for mice, increase the ability of tissues to tolerate anoxia and extend survival time under cerebral ischemic anoxia in mice. It can also inhibit the pituitrin-induced depression of S point in rats. PMID- 1304758 TI - [Anti-inflammatory and anti-bacterial functions of bezoar antipyretic tablets]. AB - Bezoar Antipyretic Tablets can inhibit markedly acute exudative inflammation. It can also inhibit markedly drug-resistant Staphylococcus aureus, etc. It has no influence on Bacillus pyocyaneus, etc. PMID- 1304759 TI - [Effects of Salvia miltiorrhiza Bunge on isolated perfused liver and portal vein of rats]. AB - The experiment results showed that Salvia miltiorrhiza (SMB) had a protective effect on the isolated perfused liver injured by CCl4 of rats, made the activity of GPT in perfusate of SMB group lower than that of intoxicated groups and relieved the hepato-pathohistologic lesions of SMB group as compared to the intoxicated group. SMB had no significant effects on both the activities of SGPT in vitro and the portal vein of rats. PMID- 1304760 TI - [18 incompatible medicaments that impair treatment]. PMID- 1304761 TI - [Age of onset of spermaturia (spermache) in 669 Mexican children and its relation to secondary sexual characteristics and height]. AB - The onset of production of spermatozoa (spermarche) indicates the beginning of reproductive capacity in men. With the purpose to establish the age of initiation of spermaturia, we performed a transversal study in 669 Mexican boys aged 9-16 years old, searching for the presence of spermatozoa in the first urine sample during five consecutive days. Besides, physical examination, including Tanner stages for genitalia and pubic hair was practiced. Spermarche (E+) occurred when the median age was 13.4 +/- 1.01 yr, the median height 155.2 +/- 8.9 cm, and the Tanner stage G2P1. The boys in Tanner stage G2P1 and E+ showed important differences in the following parameters, when they were compared with the boys in Tanner stage G2P1 and E-: height, weight, corporal surface and muscular area of the arm. The findings could be explained by the relationship between structure and function when the cellular lineages are established during different phases of development. PMID- 1304762 TI - [Acute infections, growth velocity and nutritional status in children from developing countries: a meta-analytic review]. AB - Aiming to explore the direction of the cause-effect relationship between the changes in the nutritional status, the physical growth and the selected acute infections, we performed a meta-analysis. It was based on 12 publications selected out of 993 eligible. In 6 papers (50%) a direct relationship between infections and growth velocity was found; in 5 a negative association was reported. A positive association between malnutrition (Gomez's criteria) and infection was found in 4 (33%). Two more reported no association between growth (Z score) and infection. The most remarkable confounding variables were: previous episodes of infection, duration, birth weight and feeding mode. Most of the studies did not met the criteria for causality. Better designed studies are in order to address this question. PMID- 1304763 TI - [Survival of very low birth weight newborns (less than 1,500 grams) in relation to conventional mechanical ventilation]. AB - One hundred and five very low birth weight neonates, selected through convenience sampling during 1989, were subdivided into those who received mechanical ventilation (MCV) and those who did not receive mechanical ventilation (W/O MCV) and later analyzed. The maternal morbidity in both groups were very similar; 66 of the cases were placed in group MCV and 39 in the W/O MCV. There were differences in birth weight, gestational age, severe asphyxia and hospital stay in the patients with MCV. The neonatal morbidity (SDR, intraventricular hemorrhaging, bronchopulmonary dysplasia, etc.) was more frequently seen in this group. The global mortality was 47%, all of the cases were from the ventilated group. The ventilated patients who died were in the hospital a lesser number of days and had a lesser frequency of prenatal control. We conclude that low weight neonates who require mechanical respiratory assistance have a greater risk of morbidity and mortality. The lesser weight and gestational age, the greater the risk. A group of neonates will have a lesser capacity to synthesize phospholipids and therefore a greater risk of dying. Physicians should be more attentive to the complications related to ventilated low-weight premature neonates. PMID- 1304764 TI - [Frequency of external congenital abnormalities in abortions]. AB - The purpose of this study was to calculate the incidence of external birth defects found in 1,650 aborted fetuses studied from September 1978 to February 1983 at the Department of Gynecology and Obstetrics of the University Hospital "Dr. Jose Eleuterio Gonzalez" of the U.A.N.L. Medical School. Ninety five of fetuses had external birth defects and 85 had abnormalities in annexes. The Fisher exact test was applied to find the relationship between these abnormalities; no relationship was found. 67.4% had only one birth defect; 32.1% showed several defects. Those defects which were lethal constituted 67%, the majority being of the central nervous system. Defects found in the abdominal wall took second place in frequency followed by abnormalities in either extremity and ear defects. The birth defects seen in early gestational ages differ from those seen in live newborn babies. It is important to carry out morphological and teratological studies, not only in newborns but also during the embrion and fetal periods. PMID- 1304765 TI - [Understanding and diagnosis of complex cardiopathies. I]. AB - Even pediatricians and cardiologists the complex congenital heart disease is considered to be difficult chapter. The purpose of this review is to show that complex congenital heart disease is not difficult to understand it two avenues are followed: First, a detailed explanation of the methodology used for the segmental analysis is given; all possible segmental combinations are reviewed. Second, 5 basic rules for this analysis are proposed: symmetry of the first segment, a discordant intersegmentary connection, two discordant intersegmentary connections, absence or hypoplasia of one the elements of the ventricular or arterial segment and both components of the arterial segment join one instead of the two ventricles. If these concepts are mastered, the basis for a correct diagnosis and suitable treatment are established. PMID- 1304766 TI - [Intravenous immunoglobulin in the treatment of neonatal septicemia]. AB - Thirty-seven neonates with confirmed septicemia through hemoculture were studied. Of them, 18 were treated with antibiotic and the other 19 were given 500 mg/kg of intravenous immunoglobin with a pH of 4.25 (IGIV). The greater part of the neonates in this study were full-term or near full-term. There were no differences in age, gestational age and weight, nor in mortality, the bacterias found and the clinical manifestations which were seen in both groups. Yet, the hospitalary stay was shorter for those in the group treated with IGIV (13.9 +/- 5.7 days) than in the trial group (24.4 +/- 10.3 days); as well as some clinical manifestations like diarrhea and splenomegalia (P < 0.05). The serum of the neonates from the IGIV group showed a greater capacity of opsonization and inhibition of bacterial growth than those in the trial group (P < 0.001), coinciding with an increase of 300 mg/dL in the serum levels of IgG of the group treated with IGIV from the 3rd day of the study and the C4 and B-Properdine factor serum levels from the 7th day of the study, while in the trial group, there were no changes in these factors (P < 0.001). Even though no differences were seen in the mortality rate due to septicemia, the results suggest a much shorter evolution of the illness in patients treated with IGIV. In addition, the serum of those patients treated with IGIV showed in in vitro studies, a better bacteriostatic activity and a better capacity to opsonize the bacterias isolated in the hemocultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304767 TI - [Puberty changes and various aspects of cervicovaginal infection]. AB - The changes seen during puberty tend to modify genital anatomical, biochemical, immunological and microbiological conditions, which when associated to epidemiological factors, determine the participation of different infectious agents in pre-puberty women and women going through puberty. It is convenient to be aware of the biological variations which occur in these ages since it aids the clinician in the diagnosis and treatment of pathological vaginal secretions of girls and adolescents. PMID- 1304768 TI - [Congenital hip dislocation: a public health problem in Mexico]. PMID- 1304769 TI - Variance component analysis of bristle characters in local populations of Drosophila melanogaster. AB - The genetic variabilities of sternopleural and abdominal bristle numbers existing in local natural populations were assessed. Using second chromosome lines of Drosophila melanogaster extracted from three natural populations in Japan (the Ishigakijima, Ogasawara and Aomori populations), experiments were conducted to estimate the components of genetic variances, additive and dominance variances. The following results were obtained: For both sternopleural and abdominal bristle numbers, the additive genetic variances (sigma 2A) were much larger than the dominance variances (sigma 2D) especially in the southern populations. For example, in the Ishigakijima population, for females sternopleural bristle numbers of the inversion-free chromosome group, the additive and dominance variances were estimated to be 1.255 +/- 0.2034 and 0.0552 +/- 0.0180, respectively. The magnitudes of the estimates of additive genetic variances were nearly equal from north to south. By comparing the additive genetic variances of the inversion-free chromosome group with those of the In(2L)t-carrying chromosome group, it was inferred that sufficient number of generations to achieve the equilibrium state has not passed since the introduction of a single or a small number of the In(2L)t-carrying chromosomes to the Ishigakijima population. PMID- 1304770 TI - Quantitative genetic study on sexual difference in emigration behavior of Drosophila melanogaster in a natural population. AB - A quantitative genetic analysis was conducted on emigration response behavior using 140 second chromosome lines of Drosophila melanogaster. Fourteen sets of 5 x 5 partial diallel cross experiments were made in the parental generation. The emigration activity per batch of 50 male and 50 female F1 progeny was scored with Sakai's population system. Sexual difference did not appear in the emigration activity in these experiments. A significant genotype x sex x set interaction was detected. The genetic variance components of emigration activity differed between sexes: In males, additive genetic variance of emigration activity was 0.0497 +/- 0.0092 and dominance variance, 0.0018 +/- 0.0046; in females, additive, 0.0373 +/ 0.0076 and dominance, 0.0169 +/- 0.0044. Additive genetic correlation between sexes for the emigration activity was 0.685 +/- 0.150, deviating significantly from unity. These results suggested that the genes affecting emigration activity would operate differently between sexes of D. melanogaster in natural populations. PMID- 1304771 TI - A novel cDNA clone for acid invertase in tomato fruit. AB - The sequence of a novel cDNA clone, Aiv-1, for tomato acid invertase was similar to that of TIV1 (Klann et al., 1992) for the enzyme except for a unique intron like insertion. It is considered that Aiv-1 is derived from either an alternatively spliced mRNA for an isozyme or a pre-mRNA of TIV1. PMID- 1304772 TI - Health-related behaviors in Korea: smoking, drinking, and perinatal care. AB - The prevalence of major health-related behaviors and the relationship of these factors with selected sociodemographic factors were studied in South Korea. Subjects studied were household heads and their wives from 989 households. Age standardized prevalences of smoking were 74.8% and 2.9% for men and women respectively, with no urban-rural difference. There was a tendency of younger or less-educated men smoking more heavily. The prevalence of use of alcoholic drinks were 79.8% and 26.0% for men and women respectively. More drinking was associated with a younger age and higher level of education. The mean prevalences of prenatal care, clinic or hospital delivery, and breastfeeding were 75.0%, 62.6%, and 75.2% respectively in the urban area, whereas the corresponding rates were 63.0%, 50.9%, and 81.1% in the rural area. Higher rates in prenatal care and hospital delivery were associated with a younger age and higher educational level, while breastfeeding showed the opposite trend. PMID- 1304773 TI - AIDS awareness amongst school teachers in a rural area of India. AB - One hundred and eighty-two teachers from a random selection of 15 schools in a rural area of Lucknow district of northern India were interviewed to assess their awareness and knowledge about AIDS using a pretested CARC proposed questionnaire. Observations revealed that only 79.7% of the teachers had heard about AIDS, newspapers being the main source of information. Awareness amongst graduate teachers was significantly higher than non-graduates. Many believed AIDS to be mosquito-borne and less than 2% knew that condom usage make sex safer. The study reveals the need to undertake intensive health education efforts as school teachers are an important source of health-related information for rural populations. PMID- 1304774 TI - Utilization of medically-trained birth attendants in rural Bangladesh. AB - Using case-control methodology, this study compared the characteristics of women who requested medically-trained birth attendants at home with those who did not, in order to identify constraints to service delivery and suggest program changes to increase service utilization in a rural area of Bangladesh. By several different measures, prior contact with medical professionals were much more common among cases than controls, with the greatest differences observed in the frequency of antenatal visits. At least one antenatal visit was the strongest predictor that a woman would call a medically-trained birth attendant, though primiparity, proximity to the provider, previous contact with the clinic, and education (both of the mother and her spouse) were also predictive. Recommendations include increasing contact through antenatal visits, and extending midwife coverage through training and supervision of traditional birth attendants. This study demonstrates the usefulness of case-control methodology in evaluating health care utilization. PMID- 1304775 TI - Factors contributing to the severity of childhood pedestrian injury in Perth, Western Australia. AB - Pedestrian-motor vehicle collisions that involved children aged 0 to 14 years in Perth, Western Australia were examined for the period 1980-1989 in order to identify factors which contribute to the severity of injury. Nearly half (49%) of the 1,282 children injured during this period required hospitalization, with a further 46% of the children requiring some form of medical treatment. Multivariate analysis indicated that children aged 0 to four years had a higher risk of sustaining a severe injury compared with children aged five to nine and ten to 14 years, with relative risks of 1.6 and 1.7 respectively. A greater proportion of more severe injuries occurred after 3 pm. Injuries tended to be more severe when the collision occurred on a highway or main road, and when the child was actually on the road at the point of impact. Further research on more comprehensive datasets, which consider the child's behavior at the time of injury as well as driver attributes, will provide greater insight into factors contributing to the severity of injury. PMID- 1304776 TI - Perinatal outcome amongst the Malays in an urban hospital. AB - National data show that the perinatal mortality amongst the Malays is higher than that of the Chinese but less than that of the Indians. These figures include data from both urban and rural areas. In the University Hospital, Kuala Lumpur, however, the perinatal mortality amongst the Malays was found to be the lowest; an odds-ratio of 0.72 (95% confidence limits; 0.59-0.87; P < 0.0005) when compared to the non-Malays. This occurred despite a significantly higher parity amongst the Malays. The Malays in this group of patients however, had a significantly better social class distribution. PMID- 1304778 TI - Citation for the 1993 Professor Kazue K. McLaren Leadership Achievement Award of the Asia-Pacific Academic Consortium for Public Health (APACPH) to Sidney Sax. PMID- 1304777 TI - Factors affecting the duration of breastfeeding in a rural population of Saudi Arabia. AB - A study was conducted to demonstrate factors influencing duration of breastfeeding in Al-Jamoom Western region of Saudi Arabia. Information was obtained on 476 children under the age of three years and their mothers in nine of the villages in this area. A predesigned questionnaire was administered to the mothers to obtain information on age, education, fertility parameters and antenatal care during pregnancy with the index children. Multiple regression analysis was used to analyze the effect of different biological and environmental factors on the duration of breastfeeding. The data showed that over 57% of the mothers breastfed their children for more than a year, and the mean duration of breastfeeding was 14.61 +/- 3.53 months. A considerable proportion of the mothers (42.3%) stopped breastfeeding during the first year. The most common reason for terminating breastfeeding during the first year was insufficient milk (30.9%), and recurrence of pregnancy (27.3%). A minority of the mothers (6.5%) were given advice about breastfeeding by health care professionals (physicians and nurses). Other factors such as the age of the mother, age of the infant when a supplement diet was first introduced, birth order of the child and attendance in an antenatal care clinic had a significant effect on the duration of breastfeeding. It is therefore recommended that Maternal and Child Health services must be strongly reinforced in the Primary Health Care Centers of the Ministry of Health and other health care providers. PMID- 1304779 TI - The intervention research approach to child survival. PMID- 1304780 TI - Community demonstration programs for cardiovascular disease prevention: the Asia Pacific experience. AB - Cardiovascular diseases are an important and increasing cause of death in many countries in the Asia-Pacific Region. Formal demonstration programs for the prevention of cardiovascular disease are few in number and not likely to be widely used in the future. Prevention programs focused on key risk factors are widely used in the Region and have been successful. Smoking prevention remains a high priority for all countries in the Region. PMID- 1304781 TI - Citation. Asia-Pacific Academic Consortium for Public Health Public Health Recognition Award Professor Mark Liveris. PMID- 1304782 TI - The sampling design for the Korean National Nutrition Survey. AB - Korea has been conducting the National Nutrition Survey annually since 1969. Due to the magnitude and budget of the survey, its sample size was limited to 1,000. Since 1989, however, the government has increased the size to 2,000. We developed a new sampling design suitable when budget is limited and cases to be covered are relatively very small, which has been in use since 1987. The outline of the design is introduced. Basic sampling method adopted was Probability Proportional to Size (PPS) sampling. Using the Enumeration Districts (EDs) as primary sampling units (PSU), we selected 300 EDs and constructed six identical sample sets, each having 50 ED's. From each ED, we selected 20 households. Therefore, one set has 1,000 households. Currently, two sets are being used for the survey. PMID- 1304783 TI - Getting oxygen into our hospital theatres and wards. PMID- 1304784 TI - Mortality in drunkenness offenders followed-up for 2 years. PMID- 1304785 TI - Oesophageal reconstruction using the stomach. AB - Between January 1975 and December 1989, the Cardiothoracic Unit of the University College Hospital, Ibadan (U.C.H.) carried out 47 oesophageal replacement procedures using the stomach. The ages of the patients ranged from 3 to 75 years (mean = 53.2 +/- 19.3 years). There were 24 males and 23 females. The indications for oesophageal replacement were as follows: Carcinoma of the oesophagus--34 patients (73.9%), Corrosive stricture--9 patients (17.4%), peptic stricture--1 patient (2.2%), granulomatous oesophageal lesion--1 patient (2.2%), submucous cysts--1 patient (2.2%), oesophageal perforation--1 (2.2%). Twenty patients (58.8%) with oesophageal carcinoma died between 9 and 33 days after operation. The patients with oesophageal perforation, granulomatous lesion and submucous cysts died from sepsis 8, 13 and 6 days respectively after operation due to anastomotic leak. Three patients with corrosive stricture (24%) died 10, 13 and 15 days respectively after operation. All the other 21 (54.7%) patients survived with good results as judged by the absence of dysphagia. Eight of the fourteen surviving patients with carcinoma are lost to follow-up and are presumed dead. There were two intra-operative deaths (4.3%). The operative approaches used were: Transthoracic (21 patients; 9 deaths), Transhiatal oesophagectomy (14 patients; 9 deaths) and retrosternal route (12 patients; 8 deaths). In terms of morbidity, more complications were observed with the transhiatal oesophagectomy (Orringer's technique). It is concluded that whereas oesophagoplasty with the stomach offers good results in patients with benign strictures, the results with carcinoma of the oesophagus in our environment is poor. PMID- 1304786 TI - Trends in the supply of oxygen in hospital--oxygen concentrators--Korle Bu experience. AB - The supply of Oxygen to hospitals in the West African subregion has been irregular for decades. This has added to the frustrations of Anaesthetists in the subregion. The availability of devices that absorb Nitrogen from the atmosphere, leading to an end product of high O2 concentration, appears to be the answer to chronic oxygen shortages in the developing countries. Korle Bu Hospital, Accra, has been producing its own oxygen within the hospital since 1986. Oxygen Concentrators are recommended as a solution to a chronic problem. PMID- 1304787 TI - Normal levels of glycosylated haemoglobin in pregnant Nigerian women. AB - Total glycosylated haemoglobin (HbA1) was measured in 16 healthy non-pregnant Nigerian women and in three groups of healthy women at various times during pregnancy. There was a statistically significant decrease in HbA1 in the first trimester. The values progressively increased thereafter and by term, the values were comparable to those in non-pregnant controls. The values were identical to those reported for caucasian women at similar stages of pregnancy. PMID- 1304788 TI - Causes of mortality in drunkenness offenders followed-up for 2 years. AB - Causes of death in 8 of 235 drunkenness offenders each followed up for two years, have been described. The subjects followed up were a heterogenous population of alcohol abusers. The majority were alcohol dependent irregular heavy drinkers. The main causes of death were suicide, road traffic accident, domestic accident, liver cirrhosis, hypothermia (from exposure) and ischaemic heart disease. More than one cause of death was listed in all cases. Chronic alcoholism was frequently listed. Depression was another sub-ordinate cause of death. The overall observed rate of mortality was 30 times the expected rate which was many times higher than those reported by earlier workers for alcoholics generally. These findings were discussed and it was concluded that drunkenness offenders are a particular at risk sub group of alcoholics. In view of the appreciable post mortem blood alcohol levels, it was further concluded that chronic alcoholism and the actual state of being drunk were the two major causes of death in this group of alcohol abusers. PMID- 1304789 TI - Aetiology of status epilepticus in Ibadan: a neuropathologic study. AB - In this neuropathologic study of 41 cases diagnosed as status epilepticus (SE) over a 10-year period at the University College Hospital, Ibadan (UCH), we found that the commonest cause was infection of the central nervous system (17 cases). The other aetiologic factors were: metabolic derrangement/toxic (14 cases) and cerebrovascular disease which was the most frequent cause in subjects above 12 years of age. It was encountered in 6 cases. Space occupying lesions which involved the frontal lobes were found in 4 cases. The conditions associated with the disease at death were: cerebral oedema, pulmonary oedema; pulmonary consolidation and pulmonary embolism. Our findings highlight the importance of looking for treatable conditions in patients presenting with this grave condition in this environment. PMID- 1304790 TI - Assessment of anthropometric measurements, blood analytes and liver enzymes in Ghanaian alcoholics. AB - Anthropometric measurements of alcoholics and non alcoholics of similar economic background were compared and the results reveal that there are no marked differences between the two. However, the biochemical analyses indicates that alcohol predisposes to fat storage, may contribute to iron deficiency and plays a direct etiologic role in liver disease. PMID- 1304791 TI - Clinical trial of sulbactam/ampicillin in the treatment of typhoid fever, and in vitro sensitivity of isolates to sulbactam/ampicillin and chloramphenicol. AB - A trial of Sulbactam/Ampicillin in treatment of typhoid fever was carried out while in-vitro sensitivity of the drug was compared with chloramphenicol. Sulbactam/Ampicillin was found to be effective in 11 out of 12 patients who received the drug. The 1 patient who failed to respond had intestinal perforation with peritonitis. No side effects were encountered. The in-vitro study showed that 91.7% of the isolates were sensitive to sulbactam/ampicillin compared to 75% sensitivity to chloramphenicol. The difference was however not statistically significant (P < 0.05). It is concluded that sulbactam/ampicillin is effective and safe in the treatment of typhoid infection. PMID- 1304792 TI - Glucose tolerance in psychiatric patients. AB - The relationship between glucose tolerance and psychiatric disorders is controversial. Most of the reports which have emanated mostly from North America have found either increased prevalence of diabetes amongst psychiatric patients or no relationship between psychiatric disorders and diabetes. In this study, we screened psychiatric outpatients and performed a standard oral glucose tolerance test in 29 of them. Of 59 patients studied, one was diabetic and two were found to have impaired glucose tolerance. Amongst those subjected to OGTT indices of glucose disposal were either as good as in the controls or were better than in the control subjects even though the psychiatric patients were generally more obese. Results from this study do not support the suggestion that there is increased impairment of glucose tolerance in subjects with psychiatric disorders at least in the Nigerian Africans that were tested. The improved disposal of ingested glucose in the patients is likely to be related to some of the antipsychotic drugs particularly chlorpromazine. The number of subjects tested is however small and more subjects especially those yet to be started on antipsychotic drugs will need to be studied to define in greater detail the relationship between the prevalence of glucose intolerance and psychiatric disorders in the African. PMID- 1304793 TI - Ventriculo peritoneal shunts in children. A ten year experience at the University of Nigeria Teaching Hospital, Enugu-Nigeria. AB - In a ten year period (1977--1986) one hundred and fifty children with hydrocephalus who received ventriculo-peritoneal shunt as their modality of treatment were followed up. Seventy-one per cent of these children were neonates and infants, the majority of them presenting within the first 3 months of onset of symptoms and signs. The major causes of hydrocephalus in these children were congenital malformations, meningitis, tumours and trauma. Pudenz shunt systems were favoured in the 1977--81 period, while 1982--86 period witnessed an upsurge of self devised catheters because of dwindling national economy. The latter were cheaper and more readily available. Apart from blockage of shunts which occurred more in self devised catheters, the performance of these catheters in terms of shunt infections and other complications were same in both self devised and conventional catheters. The main complications encountered were blockage and infection of the shunts, while rare complications included migration and extrusion of shunts to and from the peritoneal cavity, CSF ascites and recurrent abdominal cysts. PMID- 1304794 TI - Oral treatment of candida vaginitis: experience at the Special Treatment Clinic University College Hospital, Ibadan, Nigeria. AB - Seventy-four patients with clinical and laboratory diagnosis of candida vaginitis at Special Treatment Clinic, U.C.H., Ibadan were treated with daily dose of 400mg Ketoconazole (Nizoral) for 5 days. Forty had primary infection and 34 (46.0%) had recurrent infection. Vaginal skin infection, discharge, vulva pruritus and dyspareunia were the key symptoms and signs. Follow-up showed disappearance of findings a week following treatment except vaginal infection which was still present in 2 (2.9%) patients. Four weeks after treatment, 4--7% of the cases had one symptom or the other but more experienced dyspareunia. Mycological tests showed positive results in wet smear examination in 6.7%. Nevertheless, 80% of the 34 with recurrent infection preferred oral treatment to topical vaginal applications which they had had in the past. The implication of this result in treatment of acute and chronic vaginal candidosis in our community is discussed. PMID- 1304795 TI - Absconders from the Nigerian National Neuropsychiatric Hospital: a case control study. AB - A case-control survey of 136 absconders who left hospital without permission on a total of 170 occasions over a 15-month period was carried out. Absconding tended to be more frequent during the day time shifts (in contrast to the night shifts) and during the weekdays (in contrast to the weekends). The destination in the majority (62.4%) was the home. Absconders differed significantly from non absconders in terms of a tendency towards being single (p < 0.01), having a current or previous history of drug abuse (p < 0.01), being employed (p < 0.05) and staying longer on admission (p < 0.01). The results were discussed and explanations proffered for the significant differences. Finally, suggestions were made on ways of minimising the frequency of absconding from mental hospitals in the light of the results. PMID- 1304796 TI - Vicarious excretion of intravenous diatrizoate (Urograffin) in renal insufficiency: report of two cases. AB - Two cases of hepato-biliary excretion of intravenous sodium and meglumine diatrizoate (Urograffin 76%) are presented. One of these patients showed specification of of the gallbladder and colon while in the other case only the gallbladder was specified. In both cases there was marked deterioration of renal function. A brief review of the literature on hepatobiliary excretion of intravenous sodium and meglumine diatrizoate is given. PMID- 1304797 TI - The non-physician anaesthetist in a teaching hospital. AB - There is an overall shortage of physician anaesthetists in the West African Subregion. The non-physician anaesthetist (nurse anaesthetist) is used to provide adequate clinical service. However, in a teaching hospital setting it usually lead to the frustration of the efforts of resident physician anaesthetists. The Society of Anaesthetists of West Africa has therefore recommended that where possible nurses should not be involved in the administration of anaesthetics in the Teaching Hospitals. They should be placed out into intensive therapy units and recovery rooms. PMID- 1304798 TI - Possible contribution of free radicals and lipid peroxidations on pathogenesis of post-ischemic brain damage. AB - It has been widely accepted concept that peroxidate decomposition of membrane lipids contribute cellular damage in cerebral ischemia, and varieties of putative cascading reactions has been proposed in this regard as the underlying detrimental processes. But little is known about existence and significance of the blood born chemical mediator. In this communication, the authors tried to emphasize the prospective role of leukocyte invasion to the ischemic brain tissue. Effectiveness of some clinically applicable antioxidants against ischemic brain damage was also discussed. PMID- 1304799 TI - The role of oxygen radicals in the pathobiology of traumatic brain injury. AB - This manuscript considers some of the most prominent consequences of traumatic brain injury (TBI), namely vascular and axonal change, and evaluates the role of damaging oxygen radicals in their pathogenesis. To this end, existing as well as new data derived from traumatically injured experimental animals and humans was employed. Experimental animals were subjected to fluid-percussion brain injury. Some animals were equipped with cranial windows to allow for the functional assessment of the pial vasculature, while others received various exogenous tracers to assess blood-brain barrier status. In order to identify traumatically induced axonal change, some animals were also processed for the light and electron microscopic visualization of antibodies targeted to the neurofilament subunits. Similar immunocytochemical strategies were employed in the postmortem study of humans who had sustained severe TBI. Through these approaches, TBI was recognized to result in vascular abnormalities ranging from impaired vascular responsiveness to altered blood-brain barrier status. Typically, these vascular abnormalities continued for several hours postinjury and showed evolution which correlated with the production of damaging oxygen radicals. Importantly, the use of radical scavengers reversed these vascular abnormalities and provided protection. Traumatically induced axonal damage was also associated with evolving posttraumatic change. This involved the continued posttraumatic disassembly and misalignment of the intra-axonal neurofilament subunits which caused impaired axoplasmic transport leading to axonal swelling and detachment. Although these intra-axonal changes did not appear to be directly caused by oxygen radicals, it is suggested that the presence of oxygen radicals may exacerbate the progression of these reactive events. PMID- 1304800 TI - [Cell cycle analysis of endometrial cancer cells in vitro treated with growth factor and steroid hormone]. AB - The aim of this study was to overtake the mechanism of the control system in endometrial cancer cell line in vitro. Ishikawa cell (IK cell) and HEC-1 cell (HEC cell) derived from endometrial cancers were cultured with serum free medium (SFM-101). IK cell possessed Estrogen receptor (ER), Progesterone receptor (PR), Epidermal growth factor (EGF) and its receptor (EGFR). HEC cell had PR, EGF, and EGFR, however HEC cell did not keep ER. EGF stimulated the growth of IK cell, but the growth of HEC cell was not stimulated by EGF. S phase cells were increased by EGF in IK cell, but were not increased by EGF in HEC cell. The growth of IK cell was stimulated significantly by EGF and Estradiol-17 beta (E2) +EGF than control. However, E2+EGF did not stimulate the growth of IK cell than EGF significantly. Danazol (D) and D+EGF inhibited the growth of IK cell significantly than control. S phase cells were decreased by the treatment of D and D+EGF. From our results, EGF stimulated the growth of ER positive endometrial cancer cell, but EGF did not stimulate ER negative endometrial cancer cell. E2+EGF and EGF stimulated the growth of IK cell as a same. However, D inhibited the growth of IK cell that was stimulated by EGF. PMID- 1304801 TI - [Cytokinetic effects of cisplatin on cisplatin-resistant ovarian cancer cell lines]. AB - Cytokinetic effects of cisplatin on human ovarian cancer cell lines with natural cisplatin-resistance was examined by means of flow cytometry. These ovarian cancer cell lines derived from patients with clear cell carcinoma and serous cystadenocarcinoma were established and designated "KK" and "MH", respectively. Both KK and MH cells have shown resistance to cisplatin and IC50 of them were 0.95 microM and 3.28 microM, respectively. Cisplatin inhibited cell cycle progression at G2 +M phase up to IC50 of each cell from the analysis of cell cycle. Similar results had been obtained in the case of "KF" cell which was sensitive to cisplatin. Further studies of these cells should be performed to elucidate the mechanism of cisplatin resistance. PMID- 1304802 TI - [Anchored cell analysis and sorting (ACAS) system]. AB - Advanced biology and recent technology have provided sophisticated and objective method for analyzing biological characteristics on cells. Following that, many new instruments have developed. Diagnostic immunocytochemistry has become an accepted diagnostic tool in cell biology. In recent years, remarkable advances in technology provide a method for quantitative and objective analyses of cell characteristics. The newly developed computer assisted laser cytometer (ACAS 570) can be applied in clinical basis as well as in research laboratory. Fluorescent intensities of ancharage-dependent cells can be automatically analyzed and make it possible to separate a subpopulation of cells. This computer controlled system principally consists of argon ion laser, phase contrast microscope. Quantitative fluorescence measurements and computer graphic images can be obtained. The present paper demonstrates multiple applications of laser cytometer for evaluation of cell biology. PMID- 1304803 TI - The effect of antibiotic therapy on the oral health of cystic fibrosis children. AB - This study examined the relationship between antibiotic usage and plaque, gingivitis and dental caries experience in a group of children suffering from cystic fibrosis. Their scores for plaque, gingivitis and dental caries were compared with those of healthy control children who were individually matched on the basis of age, sex and social class. Significant negative relationships were noted between (i) antibiotic usage during the 4 weeks prior to examination and plaque and gingivitis scores, and (ii) antibiotic usage since the age of 6 years and DMFT. It is suggested that antibiotic therapy may be a major cause of the lower levels of dental disease observed in cystic fibrosis children. PMID- 1304804 TI - Effect of supervised use of a fluoride toothpaste on caries incidence in pre school children. AB - Caries prevalence of children living in Helsinki is low and little further reduction has been seen during recent years. The aim of the study was to investigate whether a supervised daily brushing at school with a fluoride toothpaste containing 1.2% sodium monofluorophosphate reduced caries incidence in a well-controlled group of nursery-school children with low caries prevalence. A total of 87 children from two nursery schools formed the test group. A group of children matched for age, baseline dfs and follow-up time, who had attended the same nursery schools just before starting this prospective study and who had brushed their teeth daily at school without toothpaste, formed a retrospective control group. After the follow-up time (mean 1.4 years), the total number of new carious surfaces was 23 in the test group (mean 0.3) and 83 in the control group (mean 0.9); the difference was significant. In the test group 72% and in the control group 62% of children were caries-free after the follow-up period. The results suggest that the use of a fluoride toothpaste as an extra daily prophylaxis reduces caries incidence in pre-school children. PMID- 1304805 TI - Enamel defects in primary canines related to traditional treatment of teething problems in Sudan. AB - In parts of Sudan and some other countries, teething is thought to be the cause of severe health problems in infants, and a traditional treatment involves lancing the alveolar process over the unerupted canines with a heated needle, a procedure known as 'haifat'. Three hundred and ninety-eight children aged 4-8 years were examined for the presence of enamel defects on primary canines, and their parents or guardians were questioned regarding past teething problems and their treatment. Two hundred and fifty-eight (65%) of the children had experienced health problems that had been attributed to teething, and 89 (22%) had been subjected to 'haifat'. 'Haifat' had been practised by all socio-economic groups, but was most prevalent in the lower groups. Enamel defects on the buccal surface of the primary canines were found in 25 (28%) of the children in the 'haifat' group and in 25 (8%) of the other children. PMID- 1304806 TI - The effect of air-polishing occlusal surfaces on the penetration of fissures by a sealant. AB - An in vitro study was performed to assess the depth of penetration of a fissure sealant after cleaning the occlusal surfaces with an air-polishing unit, and to compare the results with those obtained after cleaning with pumice and water and after no cleaning. Forty-six clinically non-carious premolars and permanent molars were randomly distributed into three groups. Following cleaning, etching and fissure sealing, the teeth were sectioned. Each section was examined under a light reflecting microscope and the depth of resin penetration was determined. Fissure cleaning with an air-polishing unit produced a statistically significant increase in depth of penetration of sealant resin, and its use as a standard cleaning method before fissure sealing is recommended. PMID- 1304807 TI - A study to compare the effectiveness of temazepam and a chloral hydrate/hydroxyzine combination in sedating paediatric dental patients. AB - The study compared the effectiveness of temazepam and a mixture of chloral hydrate and hydroxyzine in sedating 20 young children aged 20 to 60 months (mean age 38.7 months). All the children exhibited negative behaviour during a screening visit and required at least two visits for restorative treatment with the use of sedation. The children were assigned randomly to receive either 50 mg/kg of chloral hydrate with 25 mg of hydroxyzine or 0.3 mg/kg of temazepam for the first visit, and the alternate regimen for the second visit, in a double blind manner. Pulse rate and blood oxygen saturation levels were monitored before, during and after the operative procedures. All the treatment sessions were video-recorded and evaluated independently by three paediatric dentists for the degree of crying, movement, sleep and overall behaviour during specific procedures and at specific time intervals. The results showed no statistically significant differences between the two pharmacologic regimens with regard to crying, movement, sleep and overall behaviour. No significant difference in behaviour was found related to either the order of administration of the drugs or to the sex of the patients. It was concluded that 0.3 mg/kg temazepam and a mixture of 50 mg/kg chloral hydrate with 25 mg hydroxyzine had similar sedative effects on the children receiving dental treatment. PMID- 1304808 TI - British Society of Paediatric Dentistry. A policy document on sugars and dental health of children. PMID- 1304809 TI - [100 years of dentistry at the Friedrich Schiller University in Jena]. PMID- 1304810 TI - [Adolph Witzel, 100 years of the teaching of dentistry in Jena]. AB - Dr. med. Adolph Witzel has founded 100 years before the dental school of the university Jena. His personality, work and scientific performance are presented. PMID- 1304811 TI - [Periodontology in Jena--25 years of teaching, research and therapy]. AB - Periodontology is a young department and has developed in Jena in the last 25 years; since 1982 it is a part in state examination. Maintenance of teeth is possible until old age and requires periodontology as a part of therapy. Biochemically, microbiologically and immunologically methods make it possible to differentiate unlike forms of periodontitis and their special therapy. PMID- 1304812 TI - [Maxillary development after early secondary osteoplasty in complete unilateral cheilognathopalatoschisis]. AB - The paper presents the retrospective investigation of 99 cleft palate cases with unilateral clefts. The effects of two different lip closures procedure on the development of nasal, labial and maxilla region were investigated. In 50 cases the Le Mesurier lip closure procedure was followed, and in 49 cases the Millard procedure. In the Le Mesurier group a lengthening of lip was observed, while in the Millard group lip length was symmetrical. The cast analysis shows an even development of the anterior maxilla width. The cephalometric analysis also shows a favourable development in the Millard group. PMID- 1304813 TI - [Age- and sex-specific tooth and jaw measurements and their relation in the 1st mixed dentition phase--a longitudinal study on Jena children at the age of 7 1/2 to 8 1/2 years]. AB - In a longitudinal study consisting of three single examinations dental findings of 89 individuals (40 boys and 49 girls) were recorded. The aim of the study was to check up the process of dental growth and development of 7.6- to 8.6-year-old children. Age- and sex-specific differences could be established in the three occlusal dimensions by means of clinical findings and 3-d-analysis of the plaster casts. The rate of DMF teeth was remarkably low in girls and boys; the presence of malocclusions was surprisingly high. PMID- 1304814 TI - [An examination of the prognostic value of biological parameters exemplified by the crucial prognosis-relevant factors of the TPI in the patient load of the Jena Clinic in 1968 to 1991. Therapy-dependent Prognosis Index]. AB - The data of 240 patients with non-pretreated oral squamous cell carcinoma were analyzed in dependence on the tumor size (T-category), on the histologic checked lymph node status and the histopathologic grade of malignancy. There is a conformity to the results published by the DOSAK regard to the tumor size (T category). The comparison of the survival of our patients with the estimated survival rate of the TPI shows also conformable results. Differences exist in the prognostic valuation of the lymph node status by the DOSAK. The histologic verificated lymph node status and the malignancy grade will recommend as decisionsive prognostic relevant parameters. PMID- 1304815 TI - [Experimental studies of electroplating-resin bonding systems]. AB - Optimized conditioning of galvanically produced gold frameworks (Auro-Galva-Crown System) by means of Silicoater, Silicoater MD and Rocatec techniques gives rise to a reliable bond to veneering resins. After experimental stress (thermocycling) the strength of the compound could be found between 17 and 26 MPa and SEM investigations of the contact zone showed no crevices. PMID- 1304816 TI - [Inlays made from the glass ceramic Bioverit II. A clinical and scanning electron microscopic study]. AB - Inlays made of glass ceramics Bioverit II were proved just after inserting with a composite, and after 6 month's and one year. No marginal clefts were observed at clinical controls. The scanning study demonstrated excellent compound enamel composite-glass ceramics just after inserting. A 15 to 20 microns deep furrow within the composite at most of the proved teeth was recognized one year later. The margins of enamel and inlays were yet covered with composite. PMID- 1304817 TI - [The strategy in decision making for the development of an orthodontic consultation system]. AB - The high increase of information mainly because of new exact methods of examination makes it necessary to search for new possibilities of data storage, data processing and data analyzing. Orthodontic cases retrospectively assessed are taken as a knowledge-based system, and the individual case is classified by objective criteria metrically determinable as well as subjective criteria. After classification a plan of treatment can be elaborated. PMID- 1304818 TI - [Experimental studies on tissue expansion in reconstructive surgery]. AB - In the present study, a porcine model for controlled tissue expansion was investigated under the conditions or formation of extreme enlarged randomized flaps. The circulatory disturbances and necrotizing processes to be expected were evaluated immediately after flap formation by intravenous injection of fluorescein dye to predict the surviving area. Lectin histochemistry and immunohistology were performed using either the direct and indirect immunofluorescence technique (DIFT, IIFT) or immunoperoxidase techniques (POX). Over all, the expanded randomized flaps healed without complications in all animals. The acute randomized flaps showed clear necroses already after 10 days. In the thoracic area they averaged 60.3% (SD = 8.17%) and in the pelvic area 47.32% (SD = 14.11%) of the flap. The use of the fluorescein dye test in the present experiment demonstrated that the flap surviving area is significantly greater than the flap staining area. The regular expression of suprabasal keratins and epidermal lectin binding sites provides evidence for a normal epidermal cell differentiation. PMID- 1304819 TI - [The results of caries prevention in kindergartens]. AB - It was proved some years, if the program of the WHO for the oral healthy of preschool children could be realized through a complex caries prevention in 5 kindergartens of the town Jena. Since 1986 we found in 50 per cents of six years old children dentures free of caries after three years of caries prevention. PMID- 1304820 TI - On the republication of the Hamburger-Hamilton stage series. PMID- 1304821 TI - A series of normal stages in the development of the chick embryo. 1951. PMID- 1304822 TI - The stage series of the chick embryo. PMID- 1304823 TI - Pattern of expression of transforming growth factor-beta 4 mRNA and protein in the developing chicken embryo. AB - Expression of TGF-beta 4 mRNA and protein was studied in the developing chicken embryo using specific cDNA probes and antibodies for chicken TGF-beta 4. Expression of TGF-beta 4 mRNA was detected by day 4 of incubation (Hamburger and Hamilton stage 22, E4) by RNA Northern blot analysis and increased with developmental age until day 12 of incubation (stage 38, E12) where it was detected in every embryonic tissue examined, with expression being highest in smooth muscle and lowest in the kidney. The steady-state level of expression of TGF-beta 4 mRNA remained relatively constant in most embryonic tissues through day 19 (stage 45, E19). In situ hybridization analysis detected TGF-beta 4 mRNA as early as the "definitive primitive streak" stage (stage 4); during neurulation (stage 10), TGF-beta 4 mRNA was detected in all three germ layers, including neuroectoderm. Following neurulation, TGF-beta 4 mRNA was detected in the neural tube, notochord, ectoderm, endoderm, sclerotome, and myotome, but not dermotome at stage 16. By day 6 of incubation (stage 29, E6), TGF-beta 4 mRNA was localized in several tissues including heart, lung, and gizzard. Immunohistochemical staining analysis also showed expression of TGF-beta 4 protein in all three germ layers as early as stage 4 in various cell types in qualitatively similar locations as TGF-beta 4 mRNA. These results suggest that TGF-beta 4 may play an important role in the development of many tissues in the chicken. PMID- 1304824 TI - Cell interaction and its role in mesoderm cell migration during Xenopus gastrulation. AB - In the Xenopus gastrula, the mesoderm moves as a coherent cell aggregate across the blastocoel roof toward the animal pole. We show that the cohesion of the mesoderm is not only mechanically necessary, but that aggregate formation has profound effects on the migratory behavior of mesoderm cells. Whereas isolated mesoderm cells are bi- or multipolar, move stepwise and change their direction of movement frequently, aggregated mesoderm cells migrating on their in vivo substrate appear unipolar and move continuously and persistently. Moreover, only mesoderm cell aggregates, but not single cells, can follow guidance cues present in the extracellular matrix of the blastocoel roof substrate. Thus, the cohesion of the mesodermal cell mass is an essential feature of mesoderm migration during Xenopus gastrulation. We show that the Ca(2+)-dependent cell adhesion molecule U cadherin is involved in mediating this cohesion. PMID- 1304825 TI - Detection of soluble antigens by the reverse passive haemagglutination assay. AB - A series of parameters that influence coupling of antibodies to the surface of erythrocytes with Cr3+ as well as the sensitivity and specificity of the reverse passive haemagglutination (RPH) assay in various antigen-antibody systems have been studied. The optimum coating of erythrocytes with antibodies was achieved at a final concentration of 30 micrograms CrCl3/ml with a protein antibody/CrCl3 ratio of 3.66 for most antibody IgG tested (anti-human IgG, anti-human albumin, anti-human hemoglobin and anti-rabbit IgG) and of 3.16 for anti-human myoglobin. The temperature and incubation time were of 30 degrees C and 60 min, respectively. Five soluble antigens were assayed by RPH: myoglobin, hemoglobin, IgG, human albumin and rabbit IgG. The minimum detectable analyte amount ranged between 1.75 ng/ml for human myoglobin and 17.16 ng/ml for human albumin. The reaction specificity was demonstrated by the absence of cross-reactions against heterologous antigens and the RPH inhibition reaction with immune sera. By stabilization with glutaraldehyde of antibody-coated erythrocytes the shelf-life was prolonged from seven days (non-stabilized erythrocytes) up to 300 days. The reverse passive haemagglutination assay is quite simple, rapid, easy in execution and by its high sensitivity is comparable to RIA and ELISA. PMID- 1304826 TI - In vivo effects of thymic hormones (Imunotim) on immunologic parameters of patients with secondary immunodeficiency diseases. AB - In previous papers we revealed the immuno-restorative capacity of thymic hormones both in vitro and in vivo. This paper is concerned with the investigation in a phase I trial of the effects of a thymic extract (Imunotim) prepared in the Cantacuzino Institute, Bucharest upon patients with immunodeficiencies manifest as recurrent or persistent infections resistant to classical treatments. Twenty five testings were performed on 23 patients with secondary immunodepressions: carcinomas with immunodepressions following the acute phase of the disease or cytoreductive treatments (10 cases), allergic and autoimmune conditions (3 cases) and frequent, recurrent infections with prolonged evolution. In 73.9% of cases (17/23) after administration of Imunotim per os the immunologic parameters showed a tendency to return to normal values. In patients with low pre-therapy values the following were noticed: a remarkable increase of the number of lymphocytes from 1317.2 +/- 506.40 to 1961.1 +/- 899.11 (p < 0.01), of PMN from 1401.7 +/- 444.21 to 2651.0 +/- 755.31 (p < 0.01), of the absolute number of B lymphocytes from 192.0 +/- 79.00 to 444.8 +/- 299.75 (p < 0.05); the rise in the rate and absolute number of total T lymphocytes (628.2 +/- 192.81, 1041.0 +/- 441.84, respectively; p < 0.05), T helper (from 29.84 +/- 12.75% to 44.14 +/- 18.76%, respectively from 421.6 +/- 127.29 to 1058.7 +/- 411.05; p < 0.01 respectively p < 0.02) and the rise of the absolute number of T suppressor/cytotoxic lymphocytes from 92.8 +/- 97.11 to 368.3 +/- 368.53 (p < 0.05). In some patients with lymphocytosis and adenopathies the absolute lymphocyte number and the maturation of the lymphocyte populations and subpopulations in blood showed a decline. Individual variations could be noticed even within one and the some primary affection. PMID- 1304828 TI - Immunologic and antiviral therapy in herpetic keratitis. AB - A group of 113 patients with herpetic keratitis who were administered besides the classical therapy (local and general) immunologic and antiviral treatments was studied. The following Romanian non-toxic preparations were used: "SRE Immunostimulent", "Moroxidin" chlorhydrate and "Antiherpin". The control group including 120 patients received a classical treatment and the first signs of recovery appeared after 30 days; in 32% of the patients recurrences, were recorded during the first year. The recovery of the patients included in the experimental lot (113) consisted in the disappearance of congestive phenomena after 3-4 days; recurrences occurred in 14% of the patients after 1, 2 or even 4 years, especially in those who received an incomplete treatment. PMID- 1304827 TI - Serological diagnosis in human Yersinia infections. AB - Serological examinations revealed Y. enterocolitica 0:3 specific antibodies in 34% of 80 children affected by a yersiniosis epidemic at titres of 1/40-1/640 and in all sporadic Yersinia enteritis cases. Similarly, agglutinins were identified for Y. enterocolitica 0:3 and 0:9 in 3.4% of 430 appendectomized children hospitalized with painful syndrome in the right iliac fossa. In 10% of 101 patients hospitalized with arthritis and Reiter's syndrome antibodies to Y. enterocolitica 0:3 (8 cases) and Y. pseudotuberculosis (3 cases) were detected at titres of 1/80-1/640. Our results stress the importance of serological examinations in diagnosing human infections with Yersinia. PMID- 1304829 TI - Contributions to the taxonomy and biology of Clostridium difficile. AB - Clostridium difficile was incriminated by Hughes and Jarvis (1987) as a cause of intestinal infections in USA in the 1980-1984 period in 45 p. 100 of cases, whereas Salmonellae only in 12 p. 100. Four strains of this organism are studied in this paper in comparison with ten strains of C. bifermentans and six of C. sordellii, because the three species share a common antigen and have other common characteristics, as well. However, spores of C. difficile swell the bacteria and those of other bacteria (C. bifermentans and C. sordellii) do not; C. difficile does not produce indole, whereas the other species produce it. We confirmed the selective capacity of the medium of George et al. (1979) using the "alcohol shock" and as selective agents cycloserine D and cefoxitin. C. difficile proved to be most susceptible to metronidazole and rifampin. Whereas the former antibiotic was considered as a cause of post-antibiotic intestinal infections by different authors, the second was not, to our knowledge. The strain 10463 has a considerable toxicity (1000 DLM/ml for the white mouse, and pathogenicity--2000- 5000 DCL for the white mouse, as compared to 25 DCL of the other three strains). Using this toxin an antitoxic serum was obtained in horse, with a capacity of neutralizing the action of the toxin up to a dilution of 1 p. 1000. PMID- 1304830 TI - Seroepidemiological study of the circulation of influenza C virus in man. AB - The seroepidemiological study of the circulation of influenza C virus was achieved by testing HI antibodies in human sera collected from healthy subjects in Bucharest belonging to various age groups. The investigations were carried out over a two years period (October 1988--September 1990), using 3 influenza C virus strains: C/Taylor/1233/47, C/USSR/0303/77 and C/Moscow/1/84, the last two being antigenically similar. The analysis of the distribution of HI antibody values against the three influenza C virus strains showed that over October 1988--June 1989 the reported circulating viruses belonged to two distinct antigenic groups, one similar to the prototype C/Taylor/47 strains and the other to C/USSR/and/C/Moscow strains, whilst during the July 1989--September 1990 time interval viruses belonging solely to the C/USSR and C/Moscow antigenic group circulated. Similarly, one should note that circulation of influenza C viruses is not seasonal, it can appear anytime and even several times per year; this accounts for the relatively high and permanent antibody level in the population belonging to all age groups. PMID- 1304831 TI - Oncogenes and tumor suppressor genes--two different looks of the same gene? PMID- 1304832 TI - [Molecular analysis of breast cancers: recent developments]. AB - The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis. PMID- 1304833 TI - [Psychological disorders encountered during the post-transplantation period of bone marrow]. AB - Psychological issues encountered during the procedure of a bone marrow transplantation (BMT) have already been described. Anxiety, depressive behaviour and anger are reactions usually observed. For inpatients, the psychological status seems to follow the somatic status. Among patients with a kidney transplant, some authors have observed psychological problems related to the patient's impression of acquiring some of the donor's characteristics through the graft. Little is known about psychological issues following bone marrow transplantation, which requires a donor in the case of allogeneic transplantation. Thirty-nine patients (12 auto, 27 allogeneic) are included in this study. Patients had been undergoing BMT for six to eighteen months at the time of the study. All patients were in complete remission of their disease. To conduct our study, we used interviews, a rating scale of depression and anxiety, vocabulary testing, and a Rotter's scale. The patients were not suffering specifically from depression or anxiety. After BMT, they experienced both objective and subjective changes in their way of life. The majority appear to be well adapted to their new situation, and some patients have received some benefit from their experience. For a minority, the transplantation was disruptive. Psychological problems encountered in such cases were related to the personality and personal history of the patients. After an allogeneic BMT, some patients approached, by means of a complaint or a joke, the theme of transformation induced by the transplanted marrow. This suggests that psychological integration of an allogeneic marrow transplant is a complex procedure. The various components of this elaboration could be studied further by using more sophisticated means to analyse interviews. PMID- 1304834 TI - [Association studies in cancerology: the example of gene L-myc polymorphism associated with the incidence of pulmonary metastases in breast cancers]. AB - Genes, which are implicated in the pathogenesis of human tumors, may demonstrate Restriction Fragment Length Polymorphism (RFLP). Population studies of such RFLP are of potential interest for a genetic analysis of cancer susceptibility. The initial data of Krontiris et al has shown a significant increase of rare c-Ha-ras 1 alleles in individuals with tumors. Since then, other significant associations have been found between other genes RFLPs and various tumors. In this paper, we report that L-myc RFLP may prove useful in identifying breast cancer patients at high risk of developing lung metastases. PMID- 1304835 TI - [Dihydropyrimidine dehydrogenase activity in lymphocytes: predictive factor for 5 fluorouracil clearance]. AB - We previously have shown that pharmacokinetic monitoring of 5-fluorouracil (5-FU) could significantly improve the 5-FU therapeutic index when given in continuous venous infusion (Br J Cancer 59, 287-290, 1989). However, the more rational approach would be to find individual biological factors which could predict 5-FU clearance. Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme in the catabolism of 5-FU. DPD activity was measured in 57 head and neck cancer patients receiving CDDP (100 mg/m2, day 1) plus 5-FU (1 g/m2/day x 5, day 2-day 6). DPD activity was measured in lymphocytes using a radioenzymatic assay (2.5 mM MgCl2, 250 microM NADPH, 20 microM 14C-5-FU) with separation of 14C-5-FU from 14C-5-FUH2 by HPLC coupled with a radiodetector. The average DPD activity measured in lymphocytes was 0.186 +/- 0.068 nmol/min/mg protein (range 0.058-0.357) and the average 5-FU clearance (Cl) was 2,523 +/- 684 ml/min/m2 (range 1,052-4,029). A significant linear correlation was demonstrated between DPD activity and 5-FU clearance (Cl = 1,099 + 7,580 DPD, r2 = 0.613, P < 0.0001). In patients evaluated for more than one cycle (n = 18), variations in 5-FU clearance were associated with corresponding variations in DPD activity. The individual determination of DPD activity measured in lymphocytes could be useful for identifying patients at risk for altered 5-FU pharmacokinetics and could be used to adjust the optimal 5 FU dose for each patient before starting the treatment. PMID- 1304836 TI - Acute myelogenous leukemia with T-cell features. AB - From May 1985 to June 1990, 94 newly diagnosed cases of acute myelogenous leukemia (AML) were treated at the Institut Gustave-Roussy, of which four (4.3%) demonstrated mixed cell lineage. All these cases were morphologically and cytochemically considered as myelogenous leukemias according to the FAB classification. Immunophenotyping revealed in all four cases that the blast population had T-lymphoid (CD2, CD5, CD7 and cytoplasmic CD3) markers. In three of these cases, blast cells co-expressed myelogenous CD13 and CD33 markers. Cytogenetic analysis of the blast cells revealed a normal karyotype in all cases. The response to therapy has been poor. The two patients initially treated with a regimen usually used for AML did not achieve complete remission. By contrast, in three cases, complete remission was obtained with a drug combination used for lymphoblastic leukemia (in one case after failure of first line AML regimen). Only one patient remained disease-free for more than 18 months. We conclude that this form of leukemia is a distinct biological and clinical entity and may benefit form alternative therapy. PMID- 1304837 TI - [Ezhu intravenous injection in treating infantile respiratory syncytial virus pneumonia and its therapeutical mechanism]. AB - Ezhu Intravenous Injection (EII) in treating respiratory syncytial virus (RSV) pneumonia was studied. 45 patients in therapeutic group were treated with 0.04% EII in dose of 20 ml/kg/day for 7-14 days. 20 patients in the control group were treated with Huayu decoction, its efficacy on RSV pneumonia has been confirmed. The results showed that all the patients of both groups were cured and there were no statistic differences in the average days of clearing up the temperature, dyspnea and wheezing (P > 0.05). Experimental studies showed that the isolation rate of RSV on the 5th and 8th day in the therapeutic group were lower than that of infected and glucose control groups. The difference was significant (P < 0.001 and P < 0.0001). Pathological examination showed that on 5th day in infected and control group there were epithelial damages and bronchial lumen obstruction, peri bronchial and periseptal edema, eosinophilic leucocytes and inflammatory infiltrations. The endothelial cells of alveolar capillaries swelled, platelet aggregations and thrombi occurred in its lumens. On 8th day the platelet aggregations diminished, but cellular infiltrations and damages of bronchial epithelium still existed. In therapeutic group on 5th day most of the alveolar capillary endothelial cells were normal with mild edema only. The platelet aggregation were much less than the infected and control groups. No peribronchial and peri-septal edema was observed. The results of both clinical and experimental studies showed that EII had good therapeutic effect on RSV pneumonia with no adverse reaction. PMID- 1304838 TI - [Short-term effects of Angelica sinensis and nifedipine on chronic obstructive pulmonary disease in patients with pulmonary hypertension]. AB - 40 COPD cases with pulmonary hypertension (PH) in remission stage were equally divided into four groups, 10 cases in each. Group 1-4 were treated with 25% Angelica sinensis (250 ml, iv. drip, qd), nifedipine (10 mg, po, tid), both Angelica sinensis+nifedipine and blank control respectively. The study was designed to investigate the changes of hemodynamics, pulmonary function and blood gas before and after the treatments by impedance rheopneumogram, lung function examination and blood gas analysis. RESULTS: Mean pulmonary arterial pressure was decreased and cardiac output, PaO2 were increased significantly (P < 0.05 or P < 0.01) in group 3. The effects of group 3 appeared to be better than in other groups. The side effect of PaO2 lowering in group 2 was overcome in adding Angelica sinensis. PMID- 1304840 TI - [Electron microscopy observation on pre- and post-treatment skin of dorsum pedis of chyluric patient treated with heat-clearing and hemostatic drugs--the lymphangial wall damage being the pathogenesis of chyluria]. AB - Heat-clearing and hemostatic drugs were effective in treating chyluria. In order to explore the curative mechanism, a group of 10 in-patients with chyluria were chosen and treated with heat-clearing and hemostatic drugs for 45 days. Some pre- and post-treatment skin from dorsum pedis of the patients were taken off and observed under electron microscope. It showed that the walls of lymphatic capillaries were seriously damaged before treatment and rehabilitated wall after treatment. The pinocytotic vesicles were packed tightly in the endothelial cells of capillaries before treatment and their number was decreased remarkably after treatment; the mast cells were rare in number and abnormal as spindle shape before treatment and they increased in number and became round or oval in shape, the nucleus became large, the granules they contained became more in number and larger in size after treatment, lymph edema was noticed before treatment and it disappeared after treatment. The result showed that the extensive lesion of lymphangial walls is the pathogenesis of chyluria, while the rehabilitation of them is the curative mechanism. It seems that in the process of rehabilitation the mast cells act took the role of "soldier-engineer". PMID- 1304839 TI - [Clinical and experimental study of xiao er ke cuan ling oral liquid in the treatment of infantile bronchopneumonia]. AB - Xiao Er Ke Chuan Ling Oral Liquid (KCL) is a Chinese herbal preparation consisted of 10 herbs such as Prunus armeniacae, Scutelaria baicalensis, Lonicera japonica etc. 30 children suffering from bronchopneumonia and/or acute bronchitis were treated with KCL (treated group) and another 30 cases were treated with penicillin and aminophylline (control group). RESULTS: cure rate and effective rate in treated group was 26.6%, and 93.3% respectively. While in control group was 30% and 96.6% respectively. No significant differences were seen between them(P > 0.05). The pharmacodynamic experiment showed KCL had potent pharmacological action. The experiment on tracheal fragment of Guinea pig in vitro showed it caused moderately strong smooth muscle relaxation, through inhibition the effect of histamine and acetylcholine. Asthma induction experiment of Guinea pig in vivo showed KCL could significantly prolong the latent period of asthma and alleviate asthmatic symptom. Ammonium water cough induction experiment in mice showed it may apparently prolong cough latent period and reduce times of cough relapse and alleviate cough symptom. KCL had potent antipyretic effect on fever model induced by triple vaccine in rabbits. Bacteriostatic and antiviral experiment in vitro showed the drug had quite strong inhibitory effects for Streptococcus hemolyticus, Staphylococcus aureus, Flexners Dysentery bacillus, Diplococcus pneumoniae and Pseudomonas aeruginosa, and it could potently inhibit the respiratory syncytial virus. KCL is an effective drug in treating bronchopneumonia and acute bronchitis. PMID- 1304841 TI - [Abdominal diagnosis in blood-stasis syndrome]. AB - In order to make the abdomen diagnosis in Blood Statis Syndrome more objectively and quantitatively, some comprehensive quantitative analysis have been done by authors. The chief evidences between abdomen syndrome of Blood-stasis Symptoms and Blood-stasis Syndrome were correlated. The main parameters of abdomen diagnosis in Blood-stasis syndrome have been selected by computerized stepwise regression analysis in 152 patients with above-mentioned Syndromes. They were:Blood viscosity, erythrocyte deformation, extracorporeal thrombosis, platelet aggregation, thromboelastograph, electromyogram, etc. All of these can be used as objective parameters of abdomen diagnosis in Blood-stasis Syndrome to make the further study of it. PMID- 1304842 TI - [Mechanism of shen qian gujing granule in the treatment of menorrhagia]. AB - Shen Qian Gujing Granule, a Chinese herbal preparation has shown its efficacy of 87.7% in treating menorrhagia. PGE2, PGE2 alpha, TXB2 and 6-Keto-PGF1 alpha levels were measured in the endometrium and menstrual blood of both normal menstrual women and patient with menorrhagia before and after the treatment. Local TXB2 values of endometrial and menstrual blood were significantly higher in menorrhagia patients than that in normal subjects (P < 0.05). And the local PGE2 values were higher in patients accompanied with Qi Deficiency (P < 0.05) and lower in patients without Qi Deficiency (P < 0.05). After the treatment, the local TXB2, PGE2 levels normalized. It suggests that Shen Qian Gujing Granule had a biphasic regulation on local PG values which yields good results for menorrhagia. Some mechanism were discussed. PMID- 1304844 TI - [Reinforcing qi and promoting blood circulation to prevent hepatic fibrosis due to bovine serum albumin immunologic injury]. AB - 44 Wistar female rats were divided randomly into 4 groups--normal control(I), case control (II), reinforcing Qi and promoting blood circulation(III) and nourishing Yin and promoting blood circulation(IV). After 4 times of bovine serum albumin (BSA) shock injection, the group III and the group IV were medicated through gastric intubation for 40 days respectively with 300% mixture of reinforcing Qi and promoting blood circulation and 300% mixture of nourishing Yin and promoting blood circulation. The results suggest the mixture of reinforcing Qi and promoting blood circulation has the function of alleviating pathological changes of liver, reducing the content of liver collagen, improving erythrocytic function of clearing away immune complexes and regulating humoral immune response. PMID- 1304843 TI - [Research on liu wei Rehmannia oral liquid against side-effect of drugs of anti tumor chemotherapy]. AB - Using tumor-bearing mice as experimental animals, the survival rate, hematopoietic, heart, liver, kidney and immunological functions as indexes, Liu Wei Rehmannia Oral Liquid against the side-effect of drugs of anti-tumor chemotherapy (ADM, CTX, DDP, VCR and 5FU) were observed. The results showed that the survival rate in the treated group was significantly higher than that in control, the survival days were highly different (P < 0.01); the hemopoietic functions (HB, WBC, PL) in the treated group were higher also (P < 0.05 & P < 0.01); in the functions of heart, liver and kidney the treated group could protect the above-mentioned three organs (P < 0.01); in immune functions, the oral liquid could protect the NK and T-, B-Lymphocyte transformation, being inhibited by drugs of chemotherapy. In comparing with control group NK and T lymphocyte transformation were all significantly different (P < 0.01 & P < 0.05), while only 3 chemotherapy drugs were markedly different in B lymphocyte transformation (P < 0.05 & P < 0.01). The discussion indicated that Liu Wei Rehmannia Oral Liquid is effective in protecting the functions of hematopoiesis, immunity, heart, liver and kidney during chemotherapy, which provides an objective data for the clinical application. PMID- 1304846 TI - [Exploration on the problems of traditional Chinese medicine treatment of sterility]. PMID- 1304845 TI - [Effects of crude extract of earthworm on promoting blood circulation to removing stasis]. AB - The crude extract of earthworm which has a thrombolytic effect could significantly decrease the plasma fibrinogen content and euglobulin lysis time (P < 0.01). An enzymatic preparation, containing many fibrinolytic enzymes, was prepared from the crude extract by ammonium sulphate precipitation and DEAE cellulose chromatography. When administered in rabbits, the enzymatic preparation had an effect in hemorheology improvement. The experiment shows the enzymatic preparation could obviously lower the aggregation of platelets, decrease the viscosity of whole blood and plasma as well as the index of erythrocyte rigidity significantly (P < 0.001). All these effects demonstrated its ability in promoting blood circulation to remove stasis. PMID- 1304848 TI - [Progress of study on Chinese herbal drugs in treating fatty liver]. PMID- 1304847 TI - [Oxygen supply of tissues on the research of "promoting blood circulation to remove stasis"]. PMID- 1304849 TI - [Plant lectins and embryonic tissue factors as probes for studying the mechanisms of neural induction in amphibians]. AB - Using various experimental techniques, we have demonstrated that animal pole ectoderm (APE) of Rana temporaria embryos at the stage of early gastrula is a good target tissue for testing the neuralizing (N) factors. In this respect R. temporaria APE is comparable with APE of some other amphibian species. We found that concanavalin A (con A), phytohemagglutinin (PHA) and embryonic brain-derived neuralizing factor (EBDNF; a factor extracted from the chick embryonic brain and partially purified) have a pronounced N-effect on the APE of R. temporaria. In order to analyse possible mechanisms of N-action of these factors, we have cultured APE explants for 3 or 18 h in the medium containing various concentrations of con A, PHA of EBDNF. All these factors could produce neuralization in 50% explants. However, the optimal concentration and time of exposure were different. This is an evidence for different mechanisms of reception and transmission of a N-signal in each particular case. It appears that the APE consists of several cell subpopulations which differ in their threshold sensitivity to the N-effect of studied agents. PMID- 1304851 TI - [Histological variants of the hepatoid glands in representative Canidae and Cavicornia: the structural and histochemical characteristics]. AB - Both the original material and the data from literature collected in two previous papers, show a considerable diversity of structure and secretion of the glands which constitute the hepatoid gland type. According to the body of available histological (including morphometrical) and histochemical data, the authors distinguish: a) features characteristic of the hepatoid gland type only which do not appear in other types of skin glands; b) seven histological varieties within the hepatoid gland type. These seven varieties can be united, according to the laws of their structure and function, into two groups (1-3 and 5-7), with an intermediate variety (4) between them. The first group includes hepatoid glands of the "classical" structure which has been previously detaily exampled by circumanal glands of the dog: these glands possess cysts, produce a purely protein secretion; the secretion type is merocrine. The second group comprises mero-holocrine hepatoid glands which are characterized by the absence of cysts, broader excretion ducts, and a capability to produce, besides protein, considerable amounts of melanin and/or hydrophobic lipids. PMID- 1304850 TI - [The effect of 6-methyluracil on oxidative reactions in model systems of varying degrees of complexity]. AB - Effect of 6-methyluracyl (MU) on oxidative processes was studied on model systems of different degrees of complexity (methyloleate model, mitochondria isolated from rat liver, surviving slices of mammalian muscle tissues). On two former models it was shown that MU exerted antioxidant (AO) properties inferior to those of such antioxidants as ionol and K(+)-phenosan. The AO efficiency depended on the intensity of peroxide processes. The AO activity of MU was most fully realized on the model of isolated surviving slices of muscle tissue. The totality of data obtained suggests that participation of the substance in regulation of lipid peroxidation in the organism underlies its therapeutic activity in pathological states. PMID- 1304852 TI - [The interorgan distribution of tritium-labelled para-aminobenzoic acid in the body of rats after its subcutaneous injection]. AB - To study the pharmacokinetics of para-aminobenzoic acid (PABA), rats were subcutaneously injected with 3H-PABA (1 mkg/g body weight) at the stage (P7) when stimulation of outer segments of the photoreceptor cell morphogenesis is possible (Stroeva et al., 1990). The maximum labelling assayed for radioactivity by scintillation counting was observed in the liver 3 h after the injection while, in the blood the labelling was 3 times lower and, in the retina, one order lower than in the liver and blood. The label was detected in all the three types of tissue in 24 and 48 hours, being reduced by an order in comparison with each previous term of measurement. Biological structures binding 3H-PABA were not determined in the present study. PMID- 1304853 TI - [The morphogenesis of the human brain on the 27th-35th day of development with disordered neurulation]. AB - Human embryos with anomalies of brain and spinal cord were studied on 27-35th day of the development. It was established that developmental anomalies were associated with the disturbed formation of neural tube. The reconstruction of three-dimensional brain arrangement of embryos has shown the presence of different variants of nonclosed medullar tori. In mild disturbance of neurulation, there is an acceleration of organogenesis and morphological differentiation induced by the shackening of normal mechanical tensions and relaxation of neuroepithelial layers. In presence of substantial parts of open neural tube, the development of brain and ectodermal derivatives becomes disturbed to be a possible cause of anencephaly and hypotelorism. The type of disturbed neurulation inducing developmental anomalies of nervous system is suggested to be a factor which determines forms of secondary craniofacial and cranial pathology. PMID- 1304854 TI - [The principles of left-right hemispheric interactions of pharmacological preparations exemplified by Brinaldix]. AB - The effect of 4-chlor-N-(cys-2,6-dimethyl peridine)-3-sulfomoin-benzamide as an anti-hypertensive drug on left-to-right hemisphere interactions was studied on experimental animals. Its effect on hemispheres was shown to be asymmetrical. The most effective action of the drug was demonstrated on the left hemisphere of rats differing in their trends of interhemispheric interactions. PMID- 1304855 TI - [The effect of isomeric alkyl (C19--C25) methoxybenzoquinones on mitochondrial respiration]. AB - The influence of 2-methoxy-6-alkyl(C19-C25)benzoquinones-1,4 and 4-methoxy-6 alkyl(C19-C25)benzoquinones-1,2 on the respiration of isolated rat liver mitochondria has been studied. As a concentration of each of the quinones increased gradually from zero, the rate of the respiration using NAD-dependent substrates firstly increased but then decreased, 1,2-quinones being the more potent inhibitors. Concurrently, the respiratory control of mitochondria was lowered, indicating uncoupling effect of these quinones. With succinate the latter exhibited moderately accelerating effect. Uncoupled by 2,4-dinitrophenol, the respiration was stimulated by the both preparations in the presence of succinate but was suppressed when NAD-dependent substrates were used. The observed inhibitory effects have been assumed to be caused by a competition between the quinones and endogenous co-enzyme Q for the active site of NADH dehydrogenase complex of the respiratory chain. PMID- 1304856 TI - [The effect of mexidol on the dynamics of the normalization of the neurochemical and behavioral parameters of rats after deprivation of the paradoxical sleep phase]. AB - Using cytophotometric method it was shown that intraperitoneal injection of mexidol in the dose of 50 mg/kg resulted in a significant accumulation of proteins and RNA in cells of dorsal raphe nucleus (DRN) and locus coeruleus (LC) 6 hs following the injection. In rats deprived of paradoxical sleep for 24 hours, the effect of mexidol prevented the decrease in DRN proteins and RNA and even increased them, and prevented their decrease in LC. In the postdeprivation period, the beneficial effect of mexidol manifested itself in the acceleration of normalizing the levels of proteins and RNA in DRN and LC. The antistress effect of mexidol manifested itself also in the acceleration of normalizing the rat memory in the restoration period following the deprivation of paradoxical sleep. The normalization of metabolism and functional activity in serotonergic DRN is suggested to determine to a considerable extent the functional state of cerebral structures participating in the control of memory as well. PMID- 1304858 TI - Is dopamine a light-adaptive or a dark-adaptive modulator in retina? PMID- 1304857 TI - Localization and function of dopamine in the adult vertebrate retina. AB - Dopamine (DA) has satisfied many of the criteria for being a major neurochemical in vertebrate retinae. It is synthesized in amacrine and/or interplexiform cells (depending on species) and released upon membrane depolarization in a calcium dependent way. Strong evidence suggests that it is normally released within the retina during light adaptation, although flickering and not so much steady light stimuli have been found to be most effective in inducing endogenous dopamine release. DA action is not restricted to those neurones which appear to be in "direct" contact with pre-synaptic dopaminergic terminals. Neurones that are several microns away from such terminals can also be affected, presumably by short diffusion of the chemical. DA thus affects the activity of many cell types in the retina. In photoreceptors, it induces retinomotor movements, but inhibits disc shedding acting via D2 receptors, without significantly altering their electrophysiological responses. DA has two main effects upon horizontal cells: it uncouples their gap junctions and, independently, enhances the efficacy of their photoreceptor inputs, both effects involving D1 receptors. In the amphibian retina, where horizontal cells receive mixed rod and cone inputs, DA alters their balance in favour of the cone input, thus mimicking light adaptation. Light evoked DA release also appears to be responsible for potentiating the horizontal cell-->cone negative feed-back pathway responsible for generation of multi phasic, chromatic S-potentials. However, there is little information concerning action of DA upon bipolar and amacrine cells. DA effects upon ganglion cells have been investigated in mammalian (cat and rabbit) retinae. The results suggest that there are both synaptic and non-synaptic D1 and D2 receptors on all physiological types of ganglion cell tested. Although the available data cannot readily be integrated, the balance of evidence suggests that dopaminergic neurones are involved in the light/dark adaptation process in the mammalian retina. Studies of the DA system in vertebrate retinae have contributed greatly to our understanding of its role in vision as well as DA neurobiology generally in the central nervous system. For example, the effect of DA in uncoupling horizontal cells is one of the earliest demonstrations of the uncoupling of electrotonic junctions by a neurally released chemical. The many other, diverse actions of DA in the retina reviewed here are also likely to become model modes of neurochemical action in the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1304860 TI - The mode of interaction of amiloride and some of its analogues with the adenosine A1 receptor. AB - Amiloride, a potassium sparing diuretic, inhibits adenosine A1 receptor radioligand binding in calf and rat brain membranes in the low micromolar range. The drug interacted with the A1 receptor in a manner different from classical A1 ligands, but structure-activity relationship studies indicated that this inhibitory effect is not related to the ion transport inhibiting properties of amiloride (Garritsen et al., 1990a,b) In the present study, the question is addressed how amiloride interacts with the adenosine A1 receptor. Amiloride and two of its analogues, in concentrations equivalent to their Ki values in displacement studies, decrease the affinity of the A1 antagonist [3H]8 cyclopentyl-1,3-dipropylxanthine, but not the maximal binding capacity of the radioligand. Furthermore, the dissociation rate of the receptor-ligand complex is unaltered in the presence of amiloride or its analogues in a concentration exceeding the Ki value 10-fold. These characteristics argue for a purely competitive mode of interaction. The functional consequences of the interaction between amiloride analogues and the A1 receptor were investigated at the level of cyclic adenosine 3',5'-monophosphate (cAMP) formation. The amiloride analogue 5 (N-butyl-N-methyl) amiloride (MBA) reversed A1-receptor mediated inhibition of forskolin-stimulated cAMP formation in rat fat cell membranes. In this model, the antagonist potency of MBA is ca 5 microM. This value is in fair agreement with a Ki value of 3.5 microM in binding assays under similar conditions. In conclusion, amiloride inhibits A1 receptor binding in an apparently competitive manner. This suggests that the binding sites of amiloride and the classic A1 receptor ligands may at least partially overlap.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304859 TI - Effect of choline esters on the decarbamylation of dimethylcarbamyl acetylcholinesterase. AB - Acetylcholine and butyrylcholine exhibited the dose-dependent decarbamylation up to 0.2 mM, although at higher concentrations the decarbamylation degree declined. In combination with choline, butyrylcholine potentiated the choline-catalyzed decarbamylation by 30-100%, and was found to be more effective than acetylcholine in enhancing the decarbamylation. In kinetic analysis, it was observed that Ka value of choline was not remarkably altered by butyrylcholine whereas the maximum rate for decarbamylation was enhanced significantly in the presence of butyrylcholine, suggesting that butyrylcholine may affect the decarbamylation by interacting with the peripheral sites, different from the central active site which choline is known to interact with. In support of the suggestion, butyrylcholine was observed to compete with gallamine, a well known peripheral activator, and the effect of butyrylcholine was enhanced by three times at low ionic strength. In addition, acetylcholinesterase from mouse brain or bovine erythrocyte seemed to differ from electric eel enzyme in the interaction with butyrylcholine. PMID- 1304861 TI - Measurement of nerve growth factor-like immunoreactivity in human brain using an anti-mouse-NGF enzyme immunoassay. AB - Nerve growth factor (NGF) like immunoreactivity, expressed as mouse 2.5S nerve growth factor equivalents, was evaluated in three structures of the human brain post-mortem using a commercially available enzyme immunoassay. Regional differences in NGF-like immunoreactivity were observed. Highest levels were found in hippocampus (148 pg/g) compared to putamen (76 pg/g) and frontal cortex (34 pg/g). In addition, these results suggest differences in the distribution of brain NGF between human and rodent, where relatively high levels of NGF are found in the cortex. PMID- 1304862 TI - Further studies on the relationship between tyrosine supply and catecholamine production in cultured adrenal chromaffin cells. AB - To elucidate a possible role of tyrosine supply as a factor modulating catecholamine biosynthesis in the adrenergic cell, the transport of [14C]tyrosine into cultured bovine adrenal chromaffin cells was first examined, and the relationship between [14C]tyrosine transport and [14C]catecholamine formation was then investigated. Under the conditions which were routinely employed to determine the rate of catecholamine biosynthesis, tyrosine was taken up into the cells in a manner independent of extracellular Na+ and Ca2+, and this uptake was also insensitive to ouabain and various metabolic inhibitors. The stimulation of these cells with high K+ and other secretagogues caused no significant alteration in the uptake. While, tyrosine transport was markedly inhibited by tyrosine analogues and other L-aromatic amino acids, and this inhibition was accompanied by the reduction of [14C]catecholamine formation. In contrast, tyrosine transport was markedly enhanced by flavone, and this enhancement was also accompanied by the augmentation of catecholamine production under the same experimental conditions. These results seem to indicate that the transport of tyrosine into the cells may be closely related to catecholamine formation within the cells, thus providing an evidence for a possible role of tyrosine supply as one of the factors affecting catecholamine production in the adrenal chromaffin cell. PMID- 1304863 TI - Two polypeptides from Dendroaspis angusticeps venom selectively inhibit the binding of central muscarinic cholinergic receptor ligands. AB - Two new polypeptides were isolated and purified from the venom of the snake Dendroaspis angusticeps, which also contains other neuroactive peptides such as Dendrotoxins and Fasciculins. The amino acid composition of the peptides was determined and the first 10 amino acids from the MTX2 N-terminal fragment were sequenced. The so-called muscarinic toxins (MTX1 and MTX2) have been shown to inhibit the specific binding of [3H]QNB (0.15 nM), [3H]PZ (2.5 nM) and [3H]oxoM (2 nM) to bovine cerebral cortex membranes by 60, 88 and 82% respectively. In contrast, they caused only a 30% blockade of the [3H]QNB specific binding to similar membrane preparations from the brainstem. The Hill number for the [3H]PZ binding inhibition by the putative muscarinic toxin MTX2 was 0.95 suggesting homogeneity in the behaviour of the sites involved. The data from [3H]oxoM binding gave a Hill number of 0.83. The decreases in the specific binding involved increases in KD for the three different ligands (8-fold for [3H]QNB, 4 fold for [3H]PZ and 3.5-fold for [3H]oxoM) without significant changes in Bmax, except for a slight decrease in the [3H]oxoM binding sites (-19%); such results suggest that there may be a competitive inhibition between the MTXs and these ligands. The Ki for MTX2/[3H]PZ was 22.58 +/- 3.52 nM; for MTX2/[3H]oxoM, 144.9 +/- 21.07 nM and for MTX2/[3H]QNB, 134.98 +/- 18.35 nM. The labelling of MTX2 with 125I allowed direct demonstration of specific and saturable binding to bovine cerebral cortex synaptosomal membranes. In conclusion, the results reported in this study strongly support the hypotheses that the two polypeptides isolated from D. angusticeps venom selectively inhibit specific ligand binding to central muscarinic receptors, in a competitive manner at least for the antagonist [3H]PZ and that the MTX2 specifically binds to a central site that is suggested to be a muscarinic receptor of the M1 subtype. PMID- 1304864 TI - NMDA-receptor independent LTP. PMID- 1304865 TI - Interaction of sialosyl cholesterol with the cell surface of rat astrocytes and its biological activities. AB - The interaction between sialosyl cholesterol (alpha- or beta-D-N-acetyl neuraminyl cholesterol, alpha- or beta-SC) and the plasma membrane of astrocytes was investigated by the use of 14C-labeled alpha- or beta-SC. Both alpha- and beta-SC were dose-dependently and time-dependently bound to rat astrocytes. The Scatchard plot analyses showed that rat astrocytes bound apparently 9.69 x 10(9) molecules of both alpha-SC/cell (apparent Kd = 2.29 x 10(-5) M) and beta-SC/cell (apparent Kd = 5.39 x 10(-5) M) at 37 degrees C. Both the binding of alpha-SC to astrocytes and the subsequent inhibition of DNA synthesis were decreased at the low temperature (4 degrees C), and also suppressed by serum proteins including albumin. One molecule of bovine serum albumin (BSA) bound 2.3 molecules of alpha SC with the slightly lower Kd-value (8.03 x 10(-6) M) than that for the binding site on astrocytes. BSA not only suppressed the alpha-SC-binding to astrocytes but also increased its release from the cells to the culture media. Gangliosides such as GM1 and GM3 unaffected the alpha-SC-binding, promoted the small release of alpha-SC from the cell surface, and inhibited the morphological changes of astrocytes induced by alpha-SC. The mechanism of alpha-SC-binding to cultured astrocytes with reference to the effects of serum or gangliosides is discussed. PMID- 1304866 TI - Thiophosphorylated proteins in chromaffin cells are chromaffin vesicle matrix proteins. AB - Bovine adrenal chromaffin cells were incubated with inorganic thiophosphate, using a protocol similar to experiments with inorganic phosphate, in order to determine the source of previously observed thiophosphoproteins. Incubation of cultured cells with [35S]thiophosphate resulted in its incorporation into cell constituents within 2 min. SDS-PAGE of the treated cells showed incorporation of label into a broad 97-121 kDa band that was evident after 5 min of treatment and increased progressively to the 40 min exposure limit. Monolayers of chronically treated cells were fractionated into subcellular constituents. The only particulate fraction containing radiolabelled proteins was the chromaffin vesicle fraction. Two-dimensional electrophoresis of the treated cells and isolated chromaffin vesicles showed a majority of proteins in the acidic region of the first dimension gel. A fluorogram of the gel revealed two regions of radiolabelled proteins at acidic and neutral regions of the 2-D gel. These were within the boundaries of the 97-121 kDa band. The thiophosphorylated proteins were released as soluble proteins upon osmotic or freeze-thaw lysis of the vesicles. Chromaffin vesicles isolated from either cultured cells or adrenal medulla tissue were energized by 2 mM ATP but not by the analog adenosine 5'-O-(3 thiotriphosphate). The 97-121 kDa proteins in intact or lysed vesicles prepared from adrenal medulla tissue were not thiophosphorylated by either inorganic thiophosphate or adenosine 5'-O-(3-thiotriphosphate) in the presence or absence of energization by ATP. Nearly complete loss of radiolabel from matrix proteins treated with chondroitinase ABC suggests that it is a component of vesicle proteolgycans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304867 TI - Inorganic thiophosphate effects on chromaffin cell structure and function. AB - The effect was determined of replacing medium inorganic phosphate with thiophosphate on the structure and function of cultured bovine chromaffin cells. Cell cultures were incubated in normal medium containing fetal bovine serum, phosphate free medium or similar medium supplemented with inorganic phosphate or thiophosphate. In contrast to the other media, cells cultured with thiophosphate medium for 3-4 days showed seriously compromised structure and functions. The cells lost 75% of their catecholamine content and their ability to secrete remaining catecholamines in response to nicotine stimulation. Radiolabelled thiophosphate was rapidly taken up by the cells and, in long-term experiments, was incorporated largely into a 97-121 kDa protein band on SDS-PAGE. Additional minor bands were found to a lesser, variable extent. Transmission electron micrographs of cells treated with thiophosphate showed extensive depletion of chromaffin vesicles and disruption of mitochondria, suggesting that the functional damage noted with these cells could be associated with damage to mitochondria. Analysis of general cell metabolic activity by conversion of the dye (3-[3,4-dimethylthiazol-2-yl]-3,5-diphenyltetrazolium bromide) to its formazan derivative indicated increased metabolic activity at early stages of exposure to thiophosphate followed by a decline with continued exposure, supporting the argument for an overall depression of cell metabolism. Uptake of the dye neutral red, which is avidly accumulated by chromaffin cells, was also reduced for cells exposed to thiophosphate. The data suggest that thiophosphate enters chromaffin cells and disrupts energy dependent cell functions, including catecholamine storage and secretion. PMID- 1304868 TI - Role of histidine residues in the alpha-bungarotoxin binding site of the nicotinic acetylcholine receptor. AB - This paper studies the effect of histidine chemical modification of the membrane bound acetylcholine receptor from Discopyge tschudii on its specific alpha bungarotoxin binding. The acylating reagent ethoxyformic anhydride (diethyl pyrocarbonate, DEP), was used. DEP-treatment induces a loss of binding capacity, time and DEP-concentration dependent. After a 30 min period of derivatization with 2 mM final DEP-concentration, at pH 7.4, the decrease reaches 70%; the loss of binding capacity is faster at pH 7.4 than at pH 6.0, as expected, since the amount of unprotonated species is higher under the first condition. Moreover, when ethoxyformylation is carried out at different pH values, the most important neurotoxin binding decrease occurs between pH 6.0 and 8.0. Furthermore, ethoxyformylation reversion restores such capacity. Consistent with the modification of a binding site, the ethoxyformylation does not bear on the affinity but reduces the number of receptors. Ethoxyformylation in the presence of carbamylcholine shows some ligand protective effect. These results, as a whole, strongly indicate a relevant role for histidine residues at the alpha bungarotoxin binding site of the nicotinic acetylcholine receptor. PMID- 1304869 TI - Influence of the tumor mass on the valine rate constants and on valine incorporation into proteins in an experimental brain tumor model. AB - Quantitative autoradiography was used to estimate regional transfer coefficients for valine incorporation and the rate of valine (exogenous and total) incorporation into proteins in an implanted brain-tumor model (AA ascites tumor). Special attention was paid to the evaluation of the tumor mass influence on the transfer coefficients and the rate of incorporation. The size of the tumors used in this study ranged from 2 to 5 mm in diameter. Nine groups of two to three animals each were used to determine the transfer coefficient. The transfer coefficients for movement of the label between different compartments were significantly greater in the tumor than in the normal brain. There is no tumor mass effect on the transfer coefficients or the rate of valine incorporation into proteins in surrounding or remote brain structures. The ratio between specific radioactivities of the free value in tissue and plasma was also measured. Results indicate that approximately the same fraction of the total valine is recycled in cortex as in the tumor tissue. The mean rates of exogenous valine incorporation into proteins (nmol g-1 min-1) is about one order of magnitude greater in the tumor than in the contralateral parietal cortex. PMID- 1304870 TI - Purification and partial characterization of K+ channel blockers from the venom of Dendroaspis angusticeps. AB - Two polypeptides (designated DTX-A and DTX-B) were purified from crude snake venom of Dendroaspis angusticeps using gel filtration, cation exchange column chromatography and cation exchange high performance liquid chromatography, and their blocking actions of K+ channels were investigated in rat brain synaptosomes. Both DTX-A and DTX-B inhibited the voltage-dependent 42K efflux from the synaptosomes. DTX-A blocked 42K efflux of both the rapidly inactivating phase (component T) and the slowly inactivating phase (component S). The inhibitory effect of DTX-A on component T was pronounced compared with that on component S. However, DTX-B selectively blocked 42K efflux of component S. The molecular weights of DTX-A and DTX-B were estimated to be ca 10,000 by SDS polyacrylamide gel electrophoresis. The amino acid composition of these toxins is different from that of polypeptide purified from the venom of D. angusticeps (alpha-, beta-, gamma- and delta-DTX). These results suggest that DTX-A and DTX-B are new polypeptides which block voltage-dependent K+ channels selectively, and that they are useful tools for investigating the K+ channel. PMID- 1304871 TI - Dopamine receptors in human foetal brains: characterization, regulation and ontogeny of [3H]spiperone binding sites in striatum. AB - Eighteen corpora striata from normal human foetal brains ranging in gestational age from 16 to 40 weeks and five from post natal brains ranging from 23 days to 42 years were analysed for the ontogeny of dopamine receptors using [3H]spiperone as the ligand and 10 mM dopamine hydrochloride was used in blanks. Spiperone binding sites were characterized in a 40-week-old foetal brain to be dopamine receptors by the following criteria: (1) It was localized in a crude mitochondrial pellet that included synaptosomes; (2) binding was saturable at 0.8 nM concentration; (3) dopaminergic antagonists spiperone, haloperidol, pimozide, trifluperazine and chlorpromazine competed for the binding with IC50 values in the range of 0.3-14 nM while agonists--apomorphine and dopamine gave IC50 values of 2.5 and 10 microM, respectively suggesting a D2 type receptor. Epinephrine and norepinephrine inhibited the binding much less efficiently while mianserin at 10 microM and serotonin at 1 mM concentration did not inhibit the binding. Bimolecular association and dissociation rate constants for the reversible binding were 5.7 x 10(8) M-1 min-1 and 5.0 x 10(-2) min-1, respectively. Equilibrium dissociation constant was 87 pM and the KD obtained by saturation binding was 73 pM. During the foetal age 16 to 40 weeks, the receptor concentration remained in the range of 38-60 fmol/mg protein or 570-1080 fmol/g striatum but it increased two-fold postnatally reaching a maximum at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304872 TI - Preparation of noradrenaline-storing organelles from bovine sympathetic ganglia: biochemical and morphological evaluation of partly purified large dense cored vesicles. AB - Large dense cored vesicles from bovine sympathetic ganglia were isolated and partly purified. Biochemical and morphological evaluation of the present vesicle preparation revealed that it represents a convenient fraction for the characterization of perikaryal noradrenergic vesicles. Homogenates of bovine stellate ganglia were subjected to differential centrifugation and D2O-sucrose density gradient centrifugation. Biochemical evaluation of gradient fractions was performed by measuring marker enzyme activities reflecting subcellular contamination, while morphological evaluation was performed by electron microscopic analysis of the isolated fractions. Both techniques revealed that the vesicle-preparation was, at first, still considerably contaminated by mitochondria and lysosomes. An improved purification could be achieved by subjecting this fraction to an additional centrifugation under iso-osmotic conditions, also applied for the preparation of highly purified splenic nerve vesicles. The resulting vesicle-fraction was almost completely free of contaminating enzyme activities and consisted merely of large dense cored vesicles as revealed by electron microscopic observations (50-70% purity). Neuropeptide Y and chromogranin A were enriched more than 50 times as compared to the total homogenate. Although the purity of these vesicles was still not satisfactory for direct chemical analysis, this vesicle-preparation seemed very well suited for immunological characterization of perikaryal large dense cored vesicles. PMID- 1304873 TI - Modulation of cerebral acetylcholine metabolism by the dorsal diencephalic conduction system in the rat. AB - We investigated the effects of interruption of the impulse flow in the habenulopeduncular pathways by local infusion of tetrodotoxin on the acetylcholine and choline content in selected dopamine rich regions in the forebrain and midbrain in rats. The tetrodotoxin infusion caused a marked increase in acetylcholine content in the medial frontal cortex, striatum and ventral tegmental area+interpenduncular nucleus, but not in the limbic area or the substantia nigra, whereas choline content was reduced only in both the striatum and ventral tegmental area+interpeduncular nucleus. There was an increase in 3,4-dihydroxyphenylacetic acid content in the striatum after the manipulation. These findings suggest that the dorsal diencephalic conduction system may be involved in the integration of the activity of cholinergic neurons in the forebrain and midbrain regions and striatal dopanine neurons may play a role in the modulation of cholinergic neurons. PMID- 1304874 TI - 3-mercaptopropionic acid administration increases the affinity of [3H]quinuclidinyl benzilate binding to membranes of the striatum and cerebellum. AB - It is known that quinuclidinyl benzilate (QNB) binds specifically and with high affinity to the cholinergic muscarinic receptor and that behaves as a potent antagonist of this receptor. We have analysed L-[3H]QNB binding to rat CNS membranes after the administration of the convulsant 3-mercaptopropionic acid (MP) (150 mg.kg-1, i.p.). The studies were done in rats killed at two stages: during and after seizures. No changes in [3H]QNB binding to hippocampus and cerebral cortex membranes were found. [3H]QNB binding increased about 40 and 80% in striatum and cerebellum membranes, respectively. The changes were observed both in seizure and postseizures states. The study was extended to the assay of [3H]QNB binding kinetic constants in the anatomical areas modified by the convulsant. The analysis of the saturation curves indicated an increase in the binding affinity but no change in the number of binding sites. Hill number values were near the unit suggesting a non-cooperative interaction between the ligand and the receptor, and the labelling of a homogeneous population of receptor sites. The results suggest the participation of some cholinergic pathways in the development and maintenance of MP-induced seizures. PMID- 1304875 TI - Stability, quaternary structure, and folding of internal, external, and core glycosylated invertase from yeast. AB - The role of carbohydrate chains for the structure, function, stability, and folding of glycoproteins has been investigated using invertase as a model. The protein is encoded by several different genes, and its carbohydrate moiety is heterogeneous. Both properties complicate physicochemical comparisons. Here we used the temperature-sensitive sec18 secretion mutant of yeast with a single invertase gene (SUC2). This mutant produces the carbohydrate-free internal invertase, the core-glycosylated form, and, at the permissive temperature, the fully glycosylated external enzyme, all with identical protein moieties. The core glycosylated enzyme resembles the nascent glycoprotein chain that folds in the endoplasmic reticulum. Therefore, it may be considered a model for the in vivo folding of glycoproteins. In addition, because of its uniform glycosylation, it can be used to investigate the state of association of native invertase. Glycosylation is found to stabilize the protein with respect to thermal denaturation and chaotropic solvent components; the stabilizing effect does not differ for the external and the core-glycosylated forms. Unlike the internal enzyme, the glycosylated forms are protected from aggregation. Native internal invertase is a dimer (115 kDa) whereas the core-glycosylated enzyme is a mixture of dimers, tetramers, and octamers. This implies that core-glycosylation is necessary for oligomerization to tetramers and octamers. Dimerization is required and sufficient to generate enzymatic activity; further association does not alter the specific activity of core-glycosylated invertase, suggesting that the active sites of invertase are not affected by the association of the dimeric units. Reconstitution of the glycosylated and nonglycosylated forms of the enzyme after preceding guanidine denaturation depends on protein concentration. The maximum yield (approximately 80%) is obtained at pH 6-8 and protein concentrations < or = 4 micrograms/mL for the nonglycosylated and < or = 40 for the glycosylated forms of the enzyme. The lower stability of the internal enzyme is reflected by a narrower pH range of reactivation and enhanced aggregation. As indicated by the sigmoidal reactivation kinetics at low protein concentration both folding and association are rate-determining. PMID- 1304876 TI - The sequence HGLGHGHEQQHGLGHGH in the light chain of high molecular weight kininogen serves as a primary structural feature for zinc-dependent binding to an anionic surface. AB - The histidine-glycine-rich region of the light chain of cleaved high molecular weight kininogen (HK) is thought to be responsible for binding to negatively charged surfaces and initiation of the intrinsic coagulation, fibrinolytic, and kinin-forming systems. However, the specifically required amino acid sequences have not been delineated. An IgG fraction of a monoclonal antibody (MAb) C11C1 to the HK light chain was shown to inhibit by 66% the coagulant activity and by 57% the binding of HK to the anionic surface of kaolin at a concentration of 1.5 microM and 27 microM, respectively. Proteolytic fragments of HK were produced by successive digestion with human plasma kallikrein and factor XIa (FXIa). Those polypeptides that bound tightly (Kd = 0.77 nM) to a C11C1 affinity column were eluted at pH 3.0 and purified by membrane filtration. On 15% SDS polyacrylamide electrophoresis, the approximate M(r) was 7.3 kDa (range 6.2-8.1 kDa). Based on N terminal sequencing, this polypeptide (1(2)), which extends from the histidine residue 459 to a lysine at position 505, 509, 511, 512, 515, or 520, inhibits by 50% the coagulant activity expressed by HK at a concentration of 22 microM. The synthetic peptide HGLGHGH representing the N-terminal of the 1(2)) fragment was synthesized, tested, and found at 4 mM to inhibit the procoagulant activity of HK 50%. A synthetic heptadecapeptide, HGLGHGHEQQHGLGHGH (residues 459-475) included within the 1(2) fragment, and with the ability to bind zinc, inhibited 50% of the HK coagulant activity at a concentration of 325 microM in the absence and presence of added Zn2+ (30 microM). The specific binding of 125I-HK to a negatively charged surface (kaolin) was inhibited 50% by unlabeled HK (5 microM). HGLGHGH, at a concentration of 7.0 mM, inhibited the binding to kaolin by 50%. The heptadecapeptide inhibited the specific binding of 125I-HK to kaolin by 50%, at a concentration of 2.3 mM, in the absence of Zn2+. In contrast, when Zn2+ was added, the concentration to achieve 50% inhibition decreased to 630 microM, indicating that Zn2+ was required to attain a favorable conformation for binding. Moreover, the 1(2) fragment was found to inhibit 50% of the 125I-HK binding to kaolin at a concentration of 380 microM. These results suggest that residues contained within the 1(2) fragment, notably HGLGHGHEQQHGLGHGH, serves as a primary structural feature for binding to a negatively charged surface. PMID- 1304877 TI - Primary structure of a protein isolated from reef shark (Carcharhinus springeri) cartilage that is similar to the mammalian C-type lectin homolog, tetranectin. AB - During the course of characterization of low molecular weight proteins in cartilage, we have isolated a protein from reef shark (Carcharhinus springeri) cartilage that bears a striking resemblance to the tetranectin monomer originally described by Clemmensen et al. (1986, Eur. J. Biochem. 156, 327-333). The protein was isolated by extraction of neural arch cartilage with 4 M guanidine hydrochloride, dialysis of the extract to bring the guanidine to 0.4 M (reassociating proteoglycan aggregates), followed by cesium chloride density gradient removal of the proteoglycans. The amino acid sequence had 166 amino acids and a calculated molecular weight of 18,430. The shark protein was 45% identical to human tetranectin, indicating that it was in the family of mammalian C-type lectins and that it was likely to be a shark analog of human tetranectin. The function of tetranectin is unknown; it was originally isolated by virtue of its affinity for the kringle-4 domain of plasminogen. Sequence comparison of human tetranectin and the shark-derived protein gives clues to potentially important regions of the molecule. PMID- 1304878 TI - A little ancient history. PMID- 1304879 TI - Reduction of thioredoxin significantly decreases its partial specific volume and adiabatic compressibility. AB - The partial specific volume and adiabatic compressibility were determined at several temperatures for oxidized and reduced Escherichia coli thioredoxin. Oxidized thioredoxin had a partial specific volume of 0.785-0.809 mL/g at the observed upper limit for all proteins whereas the partial specific volume of reduced thioredoxin was 0.745-0.755 mL/g, a value in the range found for a majority of proteins. The adiabatic compressibility of oxidized thioredoxin was also much larger (9.8-18 x 10(-12) cm2 dyne-1) than that of the reduced protein (3.8-7.3 x 10(-12)). Apart from the region immediately around the small disulfide loop, the structures of the oxidized (X-ray, crystal) and reduced protein (nuclear magnetic resonance, solution) are reported to be very similar. It would appear that alterations in the solvent layer in contact with the protein surface must play a major role in producing these large changes in the apparent specific volumes and compressibilities in this system. Some activities of thioredoxin require the reduced structure but are not electron transfer reactions. The large changes in physical parameters reported here suggest the possibility of a reversible metabolic control function for the SS bond. PMID- 1304880 TI - The kinemage: a tool for scientific communication. AB - A "kinemage" (kinetic image) is a scientific illustration presented as an interactive computer display. Operations on the displayed kinemage respond within a fraction of a second: the entire image can be rotated in real time, parts of the display can be turned on or off, points can be identified by selecting them, and the change between different forms can be animated. A kinemage is prepared and specified by the author(s) of a journal article, in order to better communicate ideas that depend on three-dimensional information. The kinemages are distributed as plain text files of commented display lists and accompanying explanations. They are viewed and explored in an open-ended way by the reader using a simple graphics program, such as the one described here (called MAGE), which presently runs on Macintosh computers. A utility (called PREKIN) helps authors prepare the kinemages. Kinemages are being implemented under the auspices of the Innovative Technology Fund. PMID- 1304881 TI - The importance of surface loops for stabilizing an eightfold beta alpha barrel protein. AB - An important step in understanding how a protein folds is to determine those regions of the sequence that are critical to both its stability and its folding pathway. We chose phosphoribosyl anthranilate isomerase from Escherichia coli, which is a monomeric representative of the (beta alpha)8 barrel family of proteins, to construct a variant that carries an internal tandem duplication of the fifth beta alpha module. This (beta alpha)9 variant was enzymically active and therefore must have a wild-type (beta alpha)8 core. It had a choice a priori to fold to three different folding frames, which are distinguished by carrying the duplicated segment as an insert into one out of three different loops. Steady state kinetic constants, the fluorescence properties of a crucial tryptophan residue, and limited proteolysis showed that the stable (beta alpha)9 variant carries the insertion between beta-strand 5 and alpha-helix 5. This preference can be explained by the important role of loops between alpha helices and beta strands in stabilizing the structure of the enzyme. PMID- 1304882 TI - Structure of a stabilizing disulfide bridge mutant that closes the active-site cleft of T4 lysozyme. AB - The engineered disulfide bridge between residues 21 and 142 of phage T4 lysozyme spans the active-site cleft and can be used as a switch to control the activity of the enzyme (Matsumura, M. & Matthews, B.W., 1989, Science 243, 792-794). In the oxidized form the disulfide increases the melting temperature of the protein by 11 degrees C at pH 2. The crystal structure of this mutant lysozyme has been determined in both the reduced and oxidized forms. In the reduced form, the crystal structure of the mutant is shown to be extremely similar to that of wild type. In the oxidized form, however, the formation of the disulfide bridge causes the alpha-carbons of Cys 21 and Cys 142, on opposite sides of the active-site cleft, to move toward each other by 2.5 A. In association with this movement, the amino-terminal domain of the protein undergoes a rigid-body rotation of 5.1 degrees relative to the carboxy-terminal domain. This rotation occurs about an axis passing through the junction of the amino-terminal and carboxy-terminal domains and is also close to the axis that best fits the apparent thermal motion of the amino-terminal domain seen previously in crystals of wild-type lysozyme. Even though the engineered Cys 21-Cys 142 disulfide links together the amino terminal and carboxy-terminal domains of T4 lysozyme, it does not reduce the apparent mobility of the one domain relative to the other. The pronounced "hinge bending" mobility of the amino-terminal domain that is suggested by the crystallographic thermal parameters of wild-type lysozyme persists in the oxidized (and reduced) mutant structures. In the immediate vicinity of the introduced disulfide bridge the mutant structure is more mobile (or disordered) than wild type, so much so that the exact conformation of Cys 21 remains obscure. As with the previously described disulfide bridge between residues 9 and 164 of T4 lysozyme (Pjura, P.E., Matsumura, M., Wozniak, J.A., & Matthews, B.W., 1990, Biochemistry 29, 2592-2598), the engineered cross-link substantially enhances the stability of the protein without making the folded structure more rigid. PMID- 1304883 TI - Carboxylic acid-modified polyethylene: a novel support for the covalent immobilization of polypeptides for C-terminal sequencing. AB - We have developed a method for the covalent immobilization of peptides, for the purpose of C-terminal sequencing, to a novel solid support, carboxylic acid modified polyethylene (PE-COOH) film. The peptides are attached by coupling the N terminal amino group to the activated carboxyl groups of the film. Reagents for carboxyl group activation, including 1,3-dicyclohexylcarbodiimide (DCC), 1,1' carbonyldiimidazole (CDI), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP), and 1,3-diisopropylcarbodiimide (DICD) were compared. The best yields were obtained with DCC for a variety of tested peptides and averaged approximately 50%. The covalent attachment at pH 6.7 of peptides was shown to occur predominantly thorough the alpha-amino group for the peptide, SIGSLAK, which after attachment to the PE-COOH support permitted the C-terminal lysine residue to be sequenced in good yield, indicating that the epsilon-amino group of lysine is not covalently attached. This support offers a number of advantages over other solid supports, such as silica and polyvinylidene difluoride, for C-terminal sequencing including (1) stability to base and the high temperatures (65 degrees C) employed for C-terminal sequencing, (2) wettability with both aqueous and organic solvents, (3) a high capacity (1.6 nmol/mm2) for covalent coupling of polypeptides, and (4) easy divisibility into 1 x 5-mm pieces for use in our continuous flow reactor (CFR), which is also used for automated N-terminal sequencing (Shively, J.E., Miller, P., & Ronk, M., 1987, Anal. Biochem. 163, 517-529). Automated C-terminal sequencing on these supports is described in the companion paper (Bailey, J.M., Shenoy, N.R., Ronk, M., & Shively, J.E., 1992, Protein Sci. 1, 68-80). PMID- 1304884 TI - Automated carboxy-terminal sequence analysis of peptides. AB - Proteins and peptides can be sequenced from the carboxy-terminus with isothiocyanate reagents to produce amino acid thiohydantoin derivatives. Previous studies in our laboratory have focused on solution phase conditions for formation of the peptidylthiohydantoins with trimethylsilylisothiocyanate (TMS-ITC) and for hydrolysis of these peptidylthiohydantoins into an amino acid thiohydantoin derivative and a new shortened peptide capable of continued degradation (Bailey, J. M. & Shively, J. E., 1990, Biochemistry 29, 3145-3156). The current study is a continuation of this work and describes the construction of an instrument for automated C-terminal sequencing, the application of the thiocyanate chemistry to peptides covalently coupled to a novel polyethylene solid support (Shenoy, N. R., Bailey, J. M., & Shively, J. E., 1992, Protein Sci. I, 58-67), the use of sodium trimethylsilanolate as a novel reagent for the specific cleavage of the derivatized C-terminal amino acid, and the development of methodology to sequence through the difficult amino acid, aspartate. Automated programs are described for the C-terminal sequencing of peptides covalently attached to carboxylic acid modified polyethylene. The chemistry involves activation with acetic anhydride, derivatization with TMS-ITC, and cleavage of the derivatized C-terminal amino acid with sodium trimethylsilanolate. The thiohydantoin amino acid is identified by on-line high performance liquid chromatography using a Phenomenex Ultracarb 5 ODS(30) column and a triethylamine/phosphoric acid buffer system containing pentanesulfonic acid. The generality of our automated C-terminal sequencing methodology was examined by sequencing model peptides containing all 20 of the common amino acids. All of the amino acids were found to sequence in high yield (90% or greater) except for asparagine and aspartate, which could be only partially removed, and proline, which was found not be capable of derivatization. In spite of these current limitations, the methodology should be a valuable new tool for the C-terminal sequence analysis of peptides. PMID- 1304885 TI - The three-dimensional structure of the first EGF-like module of human factor IX: comparison with EGF and TGF-alpha. AB - The three-dimensional structure of the first epidermal growth factor (EGF)-like module from human factor IX has been determined in solution using two-dimensional nuclear magnetic resonance (in the absence of calcium and at pH 4.5). The structure was found to resemble closely that of EGF and the homologous transforming growth factor-alpha (TGF-alpha). Residues 60-65 form an antiparallel beta-sheet with residues 68-73. In the C-terminal subdomain a type II beta-turn is found between residues 74 and 77 and a five-residue turn is found between residues 79 and 83. Glu 78 and Leu 84 pair in an antiparallel beta-sheet conformation. In the N-terminal region a loop is found between residues 50 and 55 such that the side chains of both are positioned above the face of the beta sheet. Residues 56-60 form a turn that leads into the first strand of the beta sheet. Whereas the global fold closely resembles that of EGF, the N-terminal residues of the module (46-49) do not form a beta-strand but are ill-defined in the structure, probably due to the local flexibility of this region. The structure is discussed with reference to recent site-directed mutagenesis data, which have identified certain conserved residues as ligands for calcium. PMID- 1304886 TI - Peptide models of the Tat-TAR protein-RNA interaction. PMID- 1304887 TI - Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications. AB - Conserved structural patterns of internal water molecules and/or H-bond chains were observed and are here correlated in this review, which then describes two functional properties: equilibration of hydrostatic pressure and proton transport. Available evidence in support of these hypotheses is presented, together with suggested experiments to test them. High-resolution crystal structures of a variety of proteins were studied with interactive computer graphics. Conserved H-bonding linkages may be used as a paradigm for a rationalization of proton transport in membranes. The concept of the "proton wire," which links buried active-site amino acids with the surface of the protein raises the more general question of the functional role of the various molecular components. PMID- 1304888 TI - A detailed consideration of a principal domain of vertebrate fibrinogen and its relatives. AB - Vertebrate fibrinogen is a complex multidomained protein, the structure of which has been inferred mainly from electron microscopy and amino acid sequence studies. Among its most prominent features are two terminal globules, moieties that are mostly composed of the carboxyl-terminal two-thirds of the beta and gamma chains. Sequences homologous to the latter segments are found in several other animal proteins, always as the carboxyl-terminal contributions. An alignment of 15 amino acid sequences from various fibrinogens and related proteins has been used to make judgments about secondary structure. The nature of amino acids at each position in the alignment was used to distinguish alpha helices and beta structure on the one hand from loops and turns on the other, and the resulting assignments compared with predictions of secondary structure by other methods. Additionally, constraints imposed by the locations of cystines, carbohydrate attachment residues, and proteinase-sensitive points provided further insights into the general organization of the postulated secondary structures. Other ancillary data, including the effects of bound calcium and the locations of labeled or variant residues, were also considered. An intriguing similarity to a portion of the recently reported structure of a calcium-dependent lectin is noted. PMID- 1304889 TI - Structure of the complex between trypanosomal triosephosphate isomerase and N hydroxy-4-phosphono-butanamide: binding at the active site despite an "open" flexible loop conformation. AB - The structure of triosephosphate isomerase from Trypanosoma brucei complexed with the competitive inhibitor N-hydroxy-4-phosphono-butanamide was determined by X ray crystallography to a resolution of 2.84 A. Full occupancy binding of the inhibitor is observed only at one of the active sites of the homodimeric enzyme where the flexible loop is locked in a completely open conformation by crystal contacts. There is evidence that the inhibitor also binds to the second active site of the enzyme, but with low occupancy. The hydroxamyl group of the inhibitor forms hydrogen bonds to the side chains of Asn 11, Lys 13, and His 95, whereas each of its three methylene units is involved in nonpolar interactions with the side chain of the flexible loop residue Ile 172. Interactions between the hydroxamyl and the catalytic base Glu 167 are absent. The binding of this phosphonate inhibitor exhibits three unusual features: (1) the flexible loop is open, in contrast with the binding mode observed in eight other complexes between triosephosphate isomerase and various phosphate and phosphonate compounds; (2) compared with these complexes the present structure reveals a 1.5-A shift of the anion-binding site; (3) this is the first phosphonate inhibitor that is not forced by the enzyme into an eclipsed conformation about the P-CH2 bond. The results are discussed with respect to an ongoing drug design project aimed at the selective inhibition of glycolytic enzymes of T. brucei. PMID- 1304890 TI - Crystal structure of the Y52F/Y73F double mutant of phospholipase A2: increased hydrophobic interactions of the phenyl groups compensate for the disrupted hydrogen bonds of the tyrosines. AB - The enzyme phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 ester bond of membrane phospholipids. The highly conserved Tyr residues 52 and 73 in the enzyme form hydrogen bonds to the carboxylate group of the catalytic Asp-99. These hydrogen bonds were initially regarded as essential for the interfacial recognition and the stability of the overall catalytic network. The elimination of the hydrogen bonds involving the phenolic hydroxyl groups of the Tyr-52 and 73 by changing them to Phe lowered the stability but did not significantly affect the catalytic activity of the enzyme. The X-ray crystal structure of the double mutant Y52F/Y73F has been determined at 1.93 A resolution to study the effect of the mutation on the structure. The crystals are trigonal, space group P3(1)21, with cell parameters a = b = 46.3 A and c = 102.95 A. Intensity data were collected on a Siemens area detector, 8,024 reflections were unique with an R(sym) of 4.5% out of a total of 27,203. The structure was refined using all the unique reflections by XPLOR to a final R-factor of 18.6% for 955 protein atoms, 91 water molecules, and 1 calcium ion. The root mean square deviation for the alpha-carbon atoms between the double mutant and wild type was 0.56 A. The crystal structure revealed that four hydrogen bonds were lost in the catalytic network; three involving the tyrosines and one involving Pro-68. However, the hydrogen bonds of the catalytic triad, His-48, Asp-99, and the catalytic water, are retained. There is no additional solvent molecule at the active site to replace the missing hydroxyl groups; instead, the replacement of the phenolic OH groups by H atoms draws the Phe residues closer to the neighboring residues compared to wild type; Phe-52 moves toward His-48 and Asp-99 of the catalytic diad, and Phe-73 moves toward Met-8, both by about 0.5 A. The closing of the voids left by the OH groups increases the hydrophobic interactions compensating for the lost hydrogen bonds. The conservation of the triad hydrogen bonds and the stabilization of the active site by the increased hydrophobic interactions could explain why the double mutant has activity similar to wild type. The results indicate that the aspartyl carboxylate group of the catalytic triad can function alone without additional support from the hydrogen bonds of the two Tyr residues. PMID- 1304891 TI - A 1H NMR study of a ternary peptide complex that mimics the interaction between troponin C and troponin I. AB - The troponin I peptide N alpha-acetyl TnI (104-115) amide (TnIp) represents the minimum sequence necessary for inhibition of actomyosin ATPase activity of skeletal muscle (Talbot, J.A. & Hodges, R.S. 1981, J. Biol. Chem. 256, 2798-3802; Van Eyk, J.E. & Hodges, R.S., 1988, J. Biol. Chem. 263, 1726-1732; Van Eyk, J.E., Kay, C.M., & Hodges, R.S., 1991, Biochemistry 30, 9974-9981). In this study, we have used 1H NMR spectroscopy to compare the binding of this inhibitory TnI peptide to a synthetic peptide heterodimer representing site III and site IV of the C-terminal domain of troponin C (TnC) and to calcium-saturated skeletal TnC. The residues whose 1H NMR chemical shifts are perturbed upon TnIp binding are the same in both the site III/site IV heterodimer and TnC. These residues include F102, I104, F112, I113, I121, I149, D150, F151, and F154, which are all found in the C-terminal domain hydrophobic pocket and antiparallel beta-sheet region of the synthetic site III/site IV heterodimer and of TnC. Further, the affinity of TnIp binding to the heterodimer (Kd = 192 +/- 37 microM) was found to be similar to TnIp binding to TnC (48 +/- 18 microM [Campbell, A.P., Cachia, P.J., & Sykes, B.D., 1991, Biochem. Cell Biol. 69, 674-681]). The results indicate that binding of the inhibitory region of TnI is primarily to the C-terminal domain of TnC. The results also indicate how well the synthetic peptide heterodimer mimics the C terminal domain of TnC in structure and functional interactions. PMID- 1304892 TI - Effects of calcium on recombinant bovine chromogranin A. AB - Bovine chromogranin A, the acidic calcium-binding protein characteristic of endocrine secretory vesicles, has been expressed in Escherichia coli using the pET3a vector system under T7 polymerase control. The expressed protein is located in the bacterial cytosol and can be purified from bacterial proteins by a heat treatment step, followed by gel filtration, anion-exchange, and reversed-phase chromatography. The purified recombinant chromogranin A has an apparent M(r) of ca. 72,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in spite of its 432-amino acid polypeptide chain, consistent with observations on natural chromogranin A. The primary structure has been confirmed by mass spectral analysis of tryptic peptides, by Edman degradation of the intact protein, and by immunoreactivity with sequence-specific antibodies. Analysis by circular dichroism spectroscopy shows pH- and concentration-dependent spectra. The spectra are Ca2(+)-dependent from 5 to 40 microM. PMID- 1304893 TI - Automated carboxy-terminal sequence analysis of peptides and proteins using diphenyl phosphoroisothiocyanatidate. AB - Proteins and peptides can be sequenced from the carboxy-terminus with isothiocyanate reagents to produce amino acid thiohydantoin derivatives. Previous studies in our laboratory have focused on the automation of the thiocyanate chemistry using acetic anhydride and trimethylsilylisothiocyanate (TMS-ITC) to derivatize the C-terminal amino acid to a thiohydantoin and sodium trimethylsilanolate for specific hydrolysis of the derivatized C-terminal amino acid (Bailey, J.M., Shenoy, N.R., Ronk, M., & Shively, J.E., 1992, Protein Sci. 1, 68-80). A major limitation of this approach was the need to activate the C terminus with acetic anhydride. We now describe the use of a new reagent, diphenyl phosphoroisothiocyanatidate (DPP-ITC) and pyridine, which combines the activation and derivatization steps to produce peptidylthiohydantoins. Previous work by Kenner et al. (Kenner, G.W., Khorana, H.G., & Stedman, R.J., 1953, Chem. Soc. J., 673-678) with this reagent demonstrated slow kinetics. Several days were required for complete reaction. We show here that the inclusion of pyridine was found to promote the formation of C-terminal thiohydantoins by DPP-ITC resulting in complete conversion of the C-terminal amino acid to a thiohydantoin in less than 1 h. Reagents such as imidazole, triazine, and tetrazole were also found to promote the reaction with DPP-ITC as effectively as pyridine. General base catalysts, such as triethylamine, do not promote the reaction, but are required to convert the C-terminal carboxylic acid to a salt prior to the reaction with DPP-ITC and pyridine. By introducing the DPP-ITC reagent and pyridine in separate steps in an automated sequencer, we observed improved sequencing yields for amino acids normally found difficult to derivatize with acetic anhydride/TMS-ITC. This was particularly true for aspartic acid, which now can be sequenced in yields comparable to most of the other amino acids. Automated programs are described for the C-terminal sequencing of peptides covalently attached to carboxylic acid modified polyethylene and proteins (200 pmol to 5 nmol) noncovalently applied to Zitex (porous Teflon). The generality of our automated C-terminal sequencing methodology was examined by sequencing model peptides containing all 20 of the common amino acids. All of the amino acids tested were found to sequence in good yield except for proline, which was found not to be capable of derivatization. In spite of this limitation, the methodology should be a valuable tool for the C terminal sequence analysis of peptides and proteins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1304894 TI - Functional mapping of the surface of Escherichia coli ribose-binding protein: mutations that affect chemotaxis and transport. AB - Ribose-binding protein is a bifunctional soluble receptor found in the periplasm of Escherichia coli. Interaction of liganded binding protein with the ribose high affinity transport complex results in the transfer of ribose across the cytoplasmic membrane. Alternatively, interaction of liganded binding protein with a chemotactic signal transducer, Trg, initiates taxis toward ribose. We have generated a functional map of the surface of ribose-binding protein by creating and analyzing directed mutations of exposed residues. Residues in an area on the cleft side of the molecule including both domains have effects on transport. A portion of the area involved in transport is also essential to chemotactic function. On the opposite face of the protein, mutations in residues near the hinge are shown to affect chemotaxis specifically. PMID- 1304895 TI - Escherichia coli K12 arabinose-binding protein mutants with altered transport properties. AB - The arabinose-binding protein (ABP) of Escherichia coli binds L-arabinose in the periplasm and delivers it to a cytoplasmic membrane complex consisting of the AraG and AraH proteins, for uptake into the cell. To study the interaction between the soluble and membrane components of this periplasmic transport system, regions of the ABP surface containing the opening of the arabinose-binding cleft were subjected to site-directed mutagenesis. Thirty-eight ABP variants containing one to three amino acid substitutions were recovered. ABP variants were expressed with wild-type AraG and AraH from a plasmid, in a strain lacking the chromosomal araFGH operon, and the whole cell uptake parameters, Ven (maximum initial velocity of arabinose entry) and K(en) (concentration of arabinose yielding half maximal entry) were determined. Twenty-four mutants had normal Ven values, 3 mutants had Ven and K(en) values twice wild type, and 11 mutants had Ven and K(en) values 20-50% of wild type. Binding proteins that had altered uptake properties were each expressed, processed, and localized to the periplasm at levels equivalent to wild type. The mutant binding proteins behaved the same as wild type during purification, and each had a Kd (dissociation constant for bound arabinose) comparable to that of wild-type ABP. Mutations that resulted in altered uptake identified nine amino acids surrounding the arabinose-binding cleft, all of which are charged in the wild-type protein, and all of whose side chains project outward from the cleft. The evidence suggests that this surface of the binding protein and these nine charged loci play a major role in ABP interactions with the membrane complex. PMID- 1304896 TI - A kinetic model for binding protein-mediated arabinose transport. AB - A kinetic model is presented based on the simplest plausible mechanism for bacterial binding protein-dependent transport. The transport phenotypes of the 18 variant arabinose-binding proteins analyzed by Kehres and Hogg (1992, Protein Sci. 1, 1652-1660) (wild type and 17 mutants) are interpreted to mean that in wild-type arabinose uptake the forward transport rate (k(for)) greatly exceeds the dissociation rate (kund) of a binding protein docked with the AraG:AraH membrane complex, and that k(for) dominance is preserved in all of the binding protein surface mutants. The assumptions and predictions of the model are consistent with existing data from other periplasmic transport systems. PMID- 1304897 TI - Comprehensive sequence analysis of the 182 predicted open reading frames of yeast chromosome III. AB - With the completion of the first phase of the European yeast genome sequencing project, the complete DNA sequence of chromosome III of Saccharomyces cerevisiae has become available (Oliver, S. G., et al., 1992, Nature 357, 38-46). We have tested the predictive power of computer sequence analysis of the 176 probable protein products of this chromosome, after exclusion of six problem cases. When the results of database similarity searches are pooled with prior knowledge, a likely function can be assigned to 42% of the proteins, and a predicted three dimensional structure to a third of these (14% of the total). The function of the remaining 58% remains to be determined. Of these, about one-third have one or more probable transmembrane segments. Among the most interesting proteins with predicted functions are a new member of the type X polymerase family, a transcription factor with an N-terminal DNA-binding domain related to GAL4, a "fork head" DNA-binding domain previously known only in Drosophila and in mammals, and a putative methyltransferase. Our analysis increased the number of known significant sequence similarities on chromosome III by 13, to now 67. Although the near 40% success rate of identifying unknown protein function by sequence analysis is surprisingly high, the information gap between known protein sequences and unknown function is expected to widen and become a major bottleneck of genome projects in the near future. Based on the experience gained in this test study, we suggest that the development of an automated computer workbench for protein sequence analysis must be an important item in genome projects. PMID- 1304898 TI - A database of protein structure families with common folding motifs. AB - The availability of fast and robust algorithms for protein structure comparison provides an opportunity to produce a database of three-dimensional comparisons, called families of structurally similar proteins (FSSP). The database currently contains an extended structural family for each of 154 representative (below 30% sequence identity) protein chains. Each data set contains: the search structure; all its relatives with 70-30% sequence identity, aligned structurally; and all other proteins from the representative set that contain substructures significantly similar to the search structure. Very close relatives (above 70% sequence identity) rarely have significant structural differences and are excluded. The alignments of remote relatives are the result of pairwise all against-all structural comparisons in the set of 154 representative protein chains. The comparisons were carried out with each of three novel automatic algorithms that cover different aspects of protein structure similarity. The user of the database has the choice between strict rigid-body comparisons and comparisons that take into account interdomain motion or geometrical distortions; and, between comparisons that require strictly sequential ordering of segments and comparisons, which allow altered topology of loop connections or chain reversals. The data sets report the structurally equivalent residues in the form of a multiple alignment and as a list of matching fragments to facilitate inspection by three-dimensional graphics. If substructures are ignored, the result is a database of structure alignments of full-length proteins, including those in the twilight zone of sequence similarity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304899 TI - Stability and reconstitution of pyruvate oxidase from Lactobacillus plantarum: dissection of the stabilizing effects of coenzyme binding and subunit interaction. AB - Pyruvate oxidase from Lactobacillus plantarum is a homotetrameric flavoprotein with strong binding sites for FAD, TPP, and a divalent cation. Treatment with acid ammonium sulfate in the presence of 1.5 M KBr leads to the release of the cofactors, yielding the stable apoenzyme. In the present study, the effects of FAD, TPP, and Mn2+ on the structural properties of the apoenzyme and the reconstitution of the active holoenzyme from its constituents have been investigated. As shown by circular dichroism and fluorescence emission, as well as by Nile red binding, the secondary and tertiary structures of the apoenzyme and the holoenzyme do not exhibit marked differences. The quaternary structure is stabilized significantly in the presence of the cofactors. Size-exclusion high performance liquid chromatography and analytical ultracentrifugation demonstrate that the holoenzyme retains its tetrameric state down to 20 micrograms/mL, whereas the apoenzyme shows stepwise tetramer-dimer-monomer dissociation, with the monomer as the major component, at a protein concentration of < 20 micrograms/mL. In the presence of divalent cations, the coenzymes FAD and TPP bind to the apoenzyme, forming the inactive binary FAD or TPP complexes. Both FAD and TPP affect the quaternary structure by shifting the equilibrium of association toward the dimer or tetramer. High FAD concentrations exert significant stabilization against urea and heat denaturation, whereas excess TPP has no effect. Reconstitution of the holoenzyme from its components yields full reactivation. The kinetic analysis reveals a compulsory sequential mechanism of cofactor binding and quaternary structure formation, with TPP binding as the first step. The binary TPP complex (in the presence of 1 mM Mn2+/TPP) is characterized by a dimer-tetramer equilibrium transition with an association constant of Ka = 2 x 10(7) M-1. The apoenzyme TPP complex dimer associates with the tetrameric holoenzyme in the presence of 10 microM FAD. This association step obeys second-order kinetics with an association rate constant k = 7.4 x 10(3) M-1 s-1 at 20 degrees C. FAD binding to the tetrameric binary TPP complex is too fast to be resolved by manual mixing. PMID- 1304900 TI - Characterization of the stabilizing effect of point mutations of pyruvate oxidase from Lactobacillus plantarum: protection of the native state by modulating coenzyme binding and subunit interaction. AB - Point mutations in the gene of pyruvate oxidase from Lactobacillus plantarum, with proline residue 178 changed to serine, serine 188 to asparagine, and alanine 458 to valine, as well as a combination of the three single point mutations, lead to a significant functional stabilization of the protein. The enzyme is a tetrameric flavoprotein with tightly bound cofactors, FAD, TPP, and divalent metal ions. Thus, stabilization may be achieved either at the level of tertiary or quaternary interactions, or by enhanced cofactor binding. In order to discriminate between these alternatives, unfolding, dissociation, and cofactor binding of the mutant proteins were analyzed. The point mutations do not affect the secondary and tertiary structure, as determined by circular dichroism and protein fluorescence. Similarly, the amino acid substitutions neither modulate the enzymatic properties of the mutant proteins nor do they stabilize the structural stability of the apoenzymes. This holds true for both the local and the global structure with unfolding transitions around 2.5 M and 5 M urea, respectively. On the other hand, deactivation of the holoenzyme (by urea or temperature) is significantly decreased. The most important stabilizing effect is caused by the Ala-Val exchange in the C-terminal domain of the molecule. Its contribution is close to the value observed for the triple mutant, which exhibits maximum stability, with a shift in the thermal transition of ca. 10 degrees C. The effects of the point mutations on FAD binding and subunit association are interconnected. Because FAD binding is linked to oligomerization, the stability of the mutant apoenzyme-FAD complexes is increased. Accordingly, mutants with maximum apparent FAD binding exhibit maximum stability. Analysis of the quaternary structure of the mutant enzymes in the absence and in the presence of coenzymes gives clear evidence that both improved ligand binding and subunit interactions contribute to the observed thermal stabilization. PMID- 1304901 TI - The synthetic peptide Gly-Pro-Arg-Pro-amide limits the plasmic digestion of fibrinogen in the same fashion as calcium ion. PMID- 1304902 TI - Linderstrom-Lang and the Carlsberg Laboratory: the view of a postdoctoral fellow in 1954. PMID- 1304903 TI - Modeling the effects of mutations on the denatured states of proteins. AB - We develop a model for the reversible denaturation of proteins and for the effects of single-site mutations on the denatured states. The model is based on short chains of sequences of H (hydrophobic) and P (other) monomers configured as self-avoiding walks on the two-dimensional square lattice. The N (native) state is defined as the unique conformation of lowest contact energy, whereas the D (denatured) state is defined as the collection of all other conformations. With this model we are able to determine the exact partition function, and thus the exact native-denatured equilibrium for various solvent conditions, using the computer to exhaustively enumerate every possible configuration. Previous studies confirm that this model shows many aspects of protein-like behavior. The present study attempts to model how the denatured state (1) depends on the amino acid sequence, and (2) is changed by single-site mutations. The model accounts for two puzzling experimental results: (1) the replacement of a polar residue by a hydrophobic amino acid on the surface of a protein can destabilize a native protein, and (2) the "denaturant slope," m = partial delta G/partial c (where c is the concentration of denaturant--urea, guanidine hydrochloride), can sometimes change by as much as 30% due to a single mutation. The principal conclusion of the present study is that, under strong folding conditions, the denatured conformations that are in equilibrium with the native state are not open random configurations. Instead, they are an ensemble of highly compact conformations with a distribution that depends on the residue sequence and that can be substantially altered by single mutations. Most importantly, we conclude that mutations can exert their dominant effects on protein stability by changing the entropy of folding. PMID- 1304904 TI - Environment-specific amino acid substitution tables: tertiary templates and prediction of protein folds. AB - The local environment of an amino acid in a folded protein determines the acceptability of mutations at that position. In order to characterize and quantify these structural constraints, we have made a comparative analysis of families of homologous proteins. Residues in each structure are classified according to amino acid type, secondary structure, accessibility of the side chain, and existence of hydrogen bonds from the side chains. Analysis of the pattern of observed substitutions as a function of local environment shows that there are distinct patterns, especially for buried polar residues. The substitution data tables are available on diskette with Protein Science. Given the fold of a protein, one is able to predict sequences compatible with the fold (profiles or templates) and potentially to discriminate between a correctly folded and misfolded protein. Conversely, analysis of residue variation across a family of aligned sequences in terms of substitution profiles can allow prediction of secondary structure or tertiary environment. PMID- 1304905 TI - Atomic solvation parameters applied to molecular dynamics of proteins in solution. AB - A solvation energy function for use in the molecular simulation of proteins is proposed. It is based on the accessible surface areas of atoms in the protein and on atomic solvation parameters derived from empirical vapor-to-water free energies of transfer of amino acid side-chain analogs. The energy function and its derivatives were added to the CHARMM molecular simulation program (Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., & Karplus, M., 1983, J. Comput. Chem. 4(2), 187-217). The effect of the added energy term was evaluated by 110 ps of molecular dynamics on the 26-residue protein melittin. The melittin monomer and tetramer were studied both with and without the added term. With the added energy term the monomer partially unfolded, while the secondary structure of the tetramer was preserved, in agreement with reported experiments (Brown, L.R., Lauterwein, J., & Wuethrich, K., 1980, Biochim. Biophys. Acta 622(2), 231-244; Lauterwein, J., Brown, L.R., & Wuethrich, K., 1980, Biochim. Biophys. Acta 622(2), 219-230). PMID- 1304906 TI - Equilibrium denaturation studies of mouse beta-nerve growth factor. AB - Equilibrium denaturation of dimeric mouse beta-nerve growth factor (beta-NGF) has been studied by monitoring changes in the protein's spectroscopic characteristics. Denaturation of beta-NGF in guanidine hydrochloride and urea resulted in an altered intrinsic fluorescence emission spectrum, fluorescence depolarization, and diminished negative circular dichroism. Native-like spectroscopic properties and specific biological activity are restored when denaturant is diluted from unfolded samples, demonstrating that this process is fully reversible. However, refolding of denatured beta-NGF is dependent on the three disulfide bonds present in the native protein and does not readily occur when the disulfide bonds are reduced. Graphical analysis and nonlinear least squares fitting of beta-NGF denaturation data demonstrate that denaturation is dependent on the concentration of beta-NGF and is consistent with a two-state model involving native dimer and denatured monomer (N2 = 2D). The conformational stability of mouse beta-NGF calculated according to this model is 19.3 +/- 1.1 kcal/mol in 100 mM sodium phosphate at pH 7. Increasing the hydrogen ion concentration resulted in a 25% decrease in beta-NGF stability at pH 4 relative to pH 7. PMID- 1304907 TI - pH dependence of the reverse reaction catalyzed by phosphofructokinase I from Escherichia coli: implications for the role of Asp 127. AB - The kinetics of the reverse reaction catalyzed by Escherichia coli phosphofructokinase, i.e., the synthesis of ATP and fructose-6-phosphate from ADP and fructose-1,6-bisphosphate, have been studied at different pH values, from pH 6 to pH 9.2. Hyperbolic saturations of the enzyme are observed for both substrates. The affinity for fructose-1,6-bisphosphate decreases with pH following the ionization of a group with a pK of 6.6, whereas the catalytic rate constant and perhaps the affinity for ADP are controlled by the ionization of a group with a pK of 6. Several arguments show that the pK of 6.6 is probably that of the carboxyl group of Asp 127, whereas the pK of 6 is tentatively attributed to the carboxyl group of Asp 103. The pK of 6.6 is assigned to the carboxyl group of Asp 127 in the free enzyme, and a simple model suggests that the same group would have an abnormally high pK, above 9.6, in the complex between phosphofructokinase and fructose-1,6-bisphosphate. It is proposed that the large pK shift of more than 3 pH units upon binding of fructose-1,6-bisphosphate is due to an electrostatic repulsion that could exist between the 1-phosphate group and the carboxyl group of Asp 127, which are close to each other in the crystal structure of phosphofructokinase (Shirakihara, Y. & Evans, P.R., 1988, J. Mol. Biol. 204, 973-994). The same interpretation would also explain the much higher affinity of the enzyme for fructose-1,6-bisphosphate when Asp 127 is protonated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304908 TI - Yeast ferrochelatase: expression in a baculovirus system and purification of the expression protein. AB - The terminal step of the heme biosynthetic pathway is catalyzed by the enzyme ferrochelatase (EC 4.99.1.1). In eukaryotes this enzyme is bound to the inner mitochondrial membrane with its active site facing the matrix side of the membrane. Previously this laboratory has characterized this enzyme via kinetic and protein chemical modification techniques, and with the recent cloning of the enzyme from yeast, mouse, and human sources it now becomes possible to approach structure-function questions by using site-directed mutagenesis. Of primary significance to this is the development of an efficient expression vector. This is of particular significance for ferrochelatase, as it is a low-abundance protein whose DNA coding sequence has a very low codon bias. In the current work we describe the production of yeast ferrochelatase in a baculovirus system. This system is shown to be an excellent one in which to produce large quantities of active ferrochelatase. The expressed enzyme is membrane associated and is not released into the growth medium either during or after virus development and cell lysis. The expressed protein can be purified in a procedure that requires only 1 day and makes use of a Pharmacia Hi Trap blue affinity column. The measured Km's for the substrates mesoporphyrin and iron are the same as those reported previously for the yeast enzyme. To our knowledge this is the first example of a mitochondrial membrane protein that has been expressed in a baculovirus system. PMID- 1304909 TI - Amino acid sequence of a protease inhibitor isolated from Sarcophaga bullata determined by mass spectrometry. AB - The amino acid sequence of a protease inhibitor isolated from the hemolymph of Sarcophaga bullata larvae was determined by tandem mass spectrometry. Homology considerations with respect to other protease inhibitors with known primary structures assisted in the choice of the procedure followed in the sequence determination and in the alignment of the various peptides obtained from specific chemical cleavage at cysteines and enzyme digests of the S. bullata protease inhibitor. The resulting sequence of 57 residues is as follows: Val Asp Lys Ser Ala Cys Leu Gln Pro Lys Glu Val Gly Pro Cys Arg Lys Ser Asp Phe Val Phe Phe Tyr Asn Ala Asp Thr Lys Ala Cys Glu Glu Phe Leu Tyr Gly Gly Cys Arg Gly Asn Asp Asn Arg Phe Asn Thr Lys Glu Glu Cys Glu Lys Leu Cys Leu. PMID- 1304911 TI - Early events along the trail leading to identification of Rubisco. PMID- 1304910 TI - Characterization, primary structure, and evolution of lamprey plasma albumin. AB - The most abundant protein found in blood plasma from the sea lamprey (Petromyzon marinus) has the hallmarks of a plasma albumin: namely, high abundance, solubility in distilled water, a small number of tryptophans, and a high content of cysteines and charged residues. As in other vertebrate albumins, not all the cysteines are disulfide bonded. An unusual feature of this protein is its molecular weight of 175,000, roughly 2.5 times the size of other vertebrate albumins. Its amino acid sequence, deduced from a series of overlapping cDNA clones, can be aligned with other members of the gene family including plasma albumin, alpha-fetoprotein, and vitamin-D binding protein, confirming that it is indeed an oversized albumin. An unusual feature of the sequence is a 28-amino acid stretch consisting of a serine-threonine repeat with the general motif (STTT). Lamprey albumin contains a 23-amino acid putative signal peptide and a 6 residue putative propeptide, which, when cleaved, yield a mature protein of 1,394 amino acids with a calculated molecular weight of 157,000. The sequence also includes nine potential N-linked glycosylation sites (Asn-X-Ser/Thr), consistent with observation that lamprey albumin is a glycoprotein. If all the potential glycosylation sites were occupied by clusters of 2,000 molecular weight each, the total molecular weight would be 175,000. Like other members of the gene family, lamprey albumin is composed of a series of 190-amino acid repeats, there being seven such domains all together. Quantitative amino acid sequence comparisons of lamprey albumin with the other members of the gene family indicate that it diverged from an ancestral albumin prior to the gene duplications leading to this diverse group. This notion is confirmed by the pattern of amino acid insertions and deletions observed in a consideration of all domains that compose this family. Furthermore, it suggests that the invention of albumin antedates the vertebrate radiation. PMID- 1304912 TI - A protease-sensitive site in the proposed Ca(2+)-binding region of human serum amyloid P component and other pentraxins. AB - Serum amyloid P component (SAP) is a decamer of 10 identical 25.5-kDa subunits. Limited proteolysis of SAP with alpha-chymotrypsin cleaves the subunit into two fragments of 18 and 7.5 kDa, although the fragments stay together in the decamer under nondenaturing conditions. Proteolysis does not occur in the presence of Ca2+ (10 mM). Cleavage with alpha-chymotrypsin prevents the Ca(2+)-dependent binding of SAP to zymosan extract, nucleosomes, and DNA. The alpha-chymotrypsin cleavage site identified is in a region of SAP that is highly conserved in members of the human C-reactive protein (CRP) family of proteins (pentraxins) to which SAP belongs and is similar to the Ca(2+)-binding site in calmodulin and related Ca(2+)-binding proteins (Nguyen, N.Y., Suzuki, A., Boykins, R.A., & Liu, T.-Y., 1986, J. Biol. Chem. 261, 10456-10465). Treatment of SAP with other proteases (trypsin, Pronase, and Nagarse protease) yields fragmentation patterns upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that are similar to those obtained with alpha-chymotrypsin. Two other members of the pentraxin family of proteins, hamster female protein and rabbit CRP, also exhibit similar fragmentation patterns on SDS-PAGE when treated with the various proteases. Recently, it has been shown that the homologous protein, human CRP, is cleaved in the same homologous position as cleavage of SAP by alpha-chymotrypsin, resulting in the loss of Ca(2+)-binding (as shown by equilibrium dialysis) and Ca(2+)-dependent binding reactivities (Kinoshita, C.M., Ying, S.-C., Hugli, T.E., Siegel, J.N., Potempa, L.A., Jiang, H.J., Houghten, R.A., & Gewurz, H., 1989, Biochemistry 28, 9840-9848).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304914 TI - A proposed link between nitrogen and carbon metabolism involving protein phosphorylation in bacteria. AB - We demonstrate that certain phosphoryl transfer proteins of the bacterial phosphotransferase system (PTS), the fructose- and mannitol-specific IIA proteins or domains, are homologous to a class of proteins, one of which is known to affect transcription of some of the nitrogen-regulatory sigma 54-dependent operons in Klebsiella pneumoniae. The phosphorylatable histidyl residue in the homologous PTS proteins and the consensus sequence in the vicinity of the active site histidine are fully conserved in all members that comprise this family of proteins. A phylogenetic tree of the eight protein members of this family was constructed, and a "signature" sequence that can serve for the identification of new protein members of this family is proposed. These observations suggest that PTS-catalyzed protein phosphorylation may provide a regulatory link between carbon and nitrogen assimilation in bacteria. PMID- 1304913 TI - Identification of the adipocyte acid phosphatase as a PAO-sensitive tyrosyl phosphatase. AB - We have partially purified an 18-kDa cytoplasmic protein from 3T3-L1 cells, which dephosphorylates pNPP and the phosphorylated adipocyte lipid binding protein (ALBP), and have identified it by virtue of kinetic and immunological criteria as an acid phosphatase (EC 3.1.3.2). The cytoplasmic acid phosphatase was inactivated by phenylarsine oxide (PAO) (Kinact = 10 microM), and the inactivation could be reversed by the dithiol, 2,3-dimercaptopropanol (Kreact = 23 microM), but not the monothiol, 2-mercaptoethanol. Cloning of the human adipocyte acid phosphatase revealed that two isoforms exist, termed HAAP alpha and HAAP beta (human adipocyte acid phosphatase), which are distinguished by a 34 amino acid isoform-specific domain. Sequence analysis shows HAAP alpha and HAAP beta share 74% and 90% identity with the bovine liver acid phosphatase, respectively, and 99% identity with both isoenzymes of the human red cell acid phosphatase but no sequence similarity to the protein tyrosine phosphatases (EC 3.1.3.48). HAAP beta has been cloned into Escherichia coli, expressed, and purified as a glutathione S-transferase fusion protein. Recombinant HAAP beta was shown to dephosphorylate pNPP and phosphoALBP and to be inactivated by PAO and inhibited by vanadate (Ki = 17 microM). These results describe the adipocyte acid phosphatase as a cytoplasmic enzyme containing conformationally vicinal cysteine residues with properties that suggest it may dephosphorylate tyrosyl phosphorylated cellular proteins. PMID- 1304915 TI - The solution structure of eglin c based on measurements of many NOEs and coupling constants and its comparison with X-ray structures. AB - A high-precision solution structure of the elastase inhibitor eglin c was determined by NMR and distance geometry calculations. A large set of 947 nuclear Overhauser (NOE) distance constraints was identified, 417 of which were quantified from two-dimensional NOE spectra at short mixing times. In addition, a large number of homonuclear 1H-1H and heteronuclear 1H-15N vicinal coupling constants were used, and constraints on 42 chi 1 and 38 phi angles were obtained. Structure calculations were carried out using the distance geometry program DG II. These calculations had a high convergence rate, in that 66 out of 75 calculations converged with maximum residual NOE violations ranging from 0.17 A to 0.47 A. The spread of the structures was characterized with average root mean square deviations () between the structures and a mean structure. To calculate the unbiased toward any single structure, a new procedure was used for structure alignment. A canonical structure was calculated from the mean distances, and all structures were aligned relative to that. Furthermore, an angular order parameter S was defined and used to characterize the spread of structures in torsion angle space. To obtain an accurate estimate of the precision of the structure, the number of calculations was increased until the and the angular order parameters stabilized. This was achieved after approximately 40 calculations. The structure consists of a well-defined core whose backbone deviates from the canonical structure ca. 0.4 A, a disordered N terminal heptapeptide whose backbone deviates by 0.8-12 A, and a proteinase binding loop whose backbone deviates up to 3.0 A. Analysis of the angular order parameters and inspection of the structures indicates that a hinge-bending motion of the binding loop may occur in solution. Secondary structures were analyzed by comparison of dihedral angle patterns. The high precision of the structure allows one to identify subtle differences with four crystal structures of eglin c determined in complexes with proteinases. PMID- 1304916 TI - Characterization of the structure and properties of the His 62-->Ala and Arg 38- >Ala mutants of yeast phosphoglycerate kinase: an investigation of the catalytic and activatory sites by site-directed mutagenesis and NMR. AB - The role of two "basic patch" residues, Arg-38 and His-62, in the catalytic function and anion-dependent activation of yeast 3-phosphoglycerate kinase (PGK) was investigated by site-directed mutagenesis. Steady-state kinetics and NMR experiments were conducted to characterize the functional properties and structural integrity of the R38A and H62A mutants. The results of these studies, in combination with earlier mutagenesis experiments, suggest that Arg-38 is the only catalytically essential residue among the conserved histidines and arginines of the basic patch. It appears that, similar to the remaining basic patch residues, His-62 is important for anion-dependent activation but not for enzyme activity. Cumulative evidence from this study and from previous mutagenesis experiments suggests that the basic patch region is in effect an extended anion binding site that encompasses both the catalytic and the general anion-binding site. It is proposed that substitution of any one of the basic patch residues results in an increased localization of the catalytic site. Substrate and product may still bind to this site, but a simultaneous binding of activatory anions, required for activation, has been impaired. NMR experiments suggest that the conformational changes observed upon binding of 3-PG to wild-type PGK are necessary for anion- and substrate-dependent activation. PMID- 1304917 TI - Multiple alanine replacements within alpha-helix 126-134 of T4 lysozyme have independent, additive effects on both structure and stability. AB - In a systematic attempt to identify residues important in the folding and stability of T4 lysozyme, five amino acids within alpha-helix 126-134 were substituted by alanine, either singly or in selected combinations. Together with three alanines already present in the wild-type structure this provided a set of mutant proteins with up to eight alanines in sequence. All the variants behaved normally, suggesting that the majority of residues in the alpha-helix are nonessential for the folding of T4 lysozyme. Of the five individual alanine substitutions it is inferred that four result in slightly increased protein stability and one, the replacement of a buried leucine with alanine, substantially decreased stability. The results support the idea that alanine is a residue of high helix propensity. The change in protein stability observed for each of the multiple mutants is approximately equal to the sum of the energies associated with each of the constituent substitutions. All of the variants could be crystallized isomorphously with wild-type lysozyme, and, with one trivial exception, their structures were determined at high resolution. Substitution of the largely solvent-exposed residues Asp 127, Glu 128, and Val 131 with alanine caused essentially no change in structure except at the immediate site of replacement. Substitutions of the partially buried Asn 132 and the buried Leu 133 with alanine were associated with modest (< or = 0.4 A) structural adjustments. The structural changes seen in the multiple mutants were essentially a combination of those seen in the constituent single replacements. The different replacements therefore act essentially independently not only so far as changes in energy are concerned but also in their effect on structure. The destabilizing replacement Leu 133-->Ala made alpha-helix 126-134 somewhat less regular. Incorporation of additional alanine replacements tended to make the helix more uniform. For the penta-alanine variant a distinct change occurred in a crystal packing contact, and the "hinge-bending angle" between the amino- and carboxy terminal domains changed by 3.6 degrees. This tends to confirm that such hinge bending in T4 lysozyme is a low-energy conformational change. PMID- 1304918 TI - The disulfide bond pairing of the pheromones Er-1 and Er-2 of the ciliated protozoan Euplotes raikovi. AB - The disulfide pairings of the two Euplotes raikovi pheromones Er-1 and Er-2 have been determined by chemical and mass spectrometric analyses. Cystine-linked peptides from thermolytic digestions of the native molecules were purified by reverse-phase high performance liquid chromatography and identified in the known sequences to make the assignments. The same pairing, Cys(I)-Cys(IV), Cys(II) Cys(VI), and Cys(III)-Cys(V), was found in both pheromones, suggesting that this pattern occurs commonly throughout this family of molecules. This arrangement of disulfides indicates that the three-dimensional structure is defined by three loops, which can vary in size and charge distribution from one pheromone to another. PMID- 1304919 TI - A chromatographic approach to the determination of relative free energies of interaction between hydrophobic and amphiphilic amino acid side chains. AB - A liquid chromatographic stationary phase was prepared by covalently binding to the surface of microparticulate silica gel functionality (benzylsilane), which mimics the side chain of the amino acid phenylalanine. The chromatographic retentions of the N-acetyl C-(N'-methyl) amides of various hydrophobic and amphiphilic amino acids on this stationary phase were measured using an aqueous mobile phase. A retention order of Gly < Ala < Cys < Val < Met < Pro < Ile < Leu < Tyr < Phe < Trp is seen at room temperature. Chromatographic retentions were used to derive free energies of adsorption of the amino acid derivatives on the chromatographic support relative to that of the glycine derivative. The temperature dependencies of the retention of aromatic and aliphatic amino acid derivatives differ in curvature, indicating a qualitative difference in the absorption mechanism. An adsorption model for retention is proposed, and arguments are made as to the suitability of an adsorption model for describing the contacts between amino acid side chains during the initial steps of protein folding. PMID- 1304920 TI - Reversible dissociation and unfolding of the dimeric protein thymidylate synthase. AB - Conditions for in vitro unfolding and refolding of dimeric thymidylate synthase from Lactobacillus casei were found. Ultraviolet difference and circular dichroism spectra showed that the enzyme was completely unfolded at concentrations of urea over 5.5 M. As measured by restoration of enzyme activity, refolding was accomplished when 0.5 M potassium chloride was included in the refolding mixture. Recombination of subunits from catalytically inactive mutant homodimers to form an active hybrid dimer was achieved under these unfolding refolding conditions, demonstrating a monomer to dimer association step. PMID- 1304921 TI - Characteristics of murine protoporphyrinogen oxidase. AB - Protoporphyrinogen oxidase (EC 1.3.3.4) (PPO) is the penultimate enzyme of the heme biosynthetic pathway. Mouse PPO has been purified in low yield and kinetically characterized by this laboratory previously. A new more rapid purification procedure is described herein, and with this protein we detect a noncovalently bound flavin moiety. This flavin is present at approximately stoichiometric amounts in the purified enzyme and has been identified by its fluorescence spectrum and high performance liquid chromatography as flavin mononucleotide (FMN). Fluorescence quenching studies on the flavin yielded a Stern-Volmer quenching constant of 12.08 M-1 for iodide and 1.1 M-1 for acrylamide. Quenching of enzyme tryptophan fluorescence resulted in quenching constants of 6 M-1 and 10 M-1 for iodide and acrylamide, respectively. Plasma scans performed on purified enzyme preparations did not reveal the presence of stoichiometric amounts of protein-bound metal ions, and we were unable to detect any protein-associated pyrroloquinoline quinone (PQQ). Data from circular dichroism studies predict a secondary structure of the native protein consisting of 30.5% alpha helix, 40.5% beta sheet, 13.7% turn, and 15.3% random coil. Denaturation of PPO with urea resulted in a biphasic curve when ellipticity is plotted against urea concentration, typical of amphipathic proteins. PMID- 1304922 TI - An energy-based approach to packing the 7-helix bundle of bacteriorhodopsin. AB - Based on the heavy-atom coordinates determined by the electron microscopy for the seven main helical regions of bacteriorhodopsin with the all-trans retinal isomer, energy optimizations were carried out for helix bundles containing the all-trans retinal and 13-cis retinal chromophores, respectively. A combination of simulated annealing and energy minimization was utilized during the process of energy optimization. It was found that the 7-helix bundle containing the all trans isomer is about 10 kcal/mol lower in conformational energy than that containing the 13-cis isomer. An energetic analysis indicates that such a difference in energy is consistent with the observation that absorption of a 570 nm proton is required for the conversion of a bacteriorhodopsin from its all trans to 13-cis form. It was also found that the above conversion process is accompanied by a significant conformational perturbation around the chromophore, as reflected by the fact that the beta-ionone ring of retinal moves about 5.6 A along the direction perpendicular to the membrane plane. This is consistent with the observation by Fodor et al. (Fodor, S.P.A., Ames, J.B., Gebhard, R., van der Berg, E.M.M., Stoeckenius, W., Lugtenburg, J., & Mathies, R.A., 1988, Biochemistry 27, 7097-7101). Furthermore, it is interesting to observe that although the retinal chromophore undergoes a significant change in its spatial position, the orientation of its transition dipole changes only slightly, in accord with experimental observations. In other words, even though orientation of the retinal transition dipole is very restricted, there is sufficient room, and degrees of freedom, for the retinal chromophore to readjust its position considerably. This finding provides new insight into the subtle change of the retinal microenvironment, which may be important for revealing the proton-pumping mechanism of bacteriorhodopsin. The importance of electrostatic and nonbonded interactions in stabilizing the 7-helix bundle structure has also been analyzed. Electrostatic interactions favor an antiparallel arrangement among adjacent helices. Nonbonded interactions, however, drive most of the closely packed helices into an arrangement in which the packing angles lie around -160 degrees, a value very near the -154 degrees value computed earlier as the most favorable packing arrangement of two poly(Ala) alpha-helices (Chou, K.-C., Nemethy, G., & Scheraga, H.A., 1983, J. Phys. Chem. 87, 2869-2881). The structural features of the 7-helix bundle and their relationship to those found in typical 4-helix bundle proteins are also discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1304923 TI - Nurse managers: evolving roles in achieving quality. PMID- 1304924 TI - Seven essential questions about software for quality programs. PMID- 1304925 TI - Quality Q&A. How can I motivate my staff members to participate in quality efforts? PMID- 1304926 TI - Are your patients satisfied? PMID- 1304927 TI - Monitoring infected i.v. sites. PMID- 1304928 TI - Follow-up phone calls: a monitoring opportunity. Interview by Patricia Schroeder. PMID- 1304929 TI - JCAHO: de-mystifying the staff development role. PMID- 1304930 TI - Learning from dinosaurs. PMID- 1304931 TI - Shared gain: town-gown collaboration. PMID- 1304932 TI - Recruitment and retention. Four ways to make a difference. PMID- 1304933 TI - Consulting for results. PMID- 1304934 TI - Computers and you. PMID- 1304936 TI - Self-directed learning: video programs. PMID- 1304935 TI - To test or not to test? These are the questions. PMID- 1304937 TI - Job sharing: a viable option. PMID- 1304938 TI - Virulence factors in Serratia marcescens: cell-bound hemolysin and aerobactin. AB - 1. A total of 60 nosocomial isolates of Serratia marcescens were screened for the presence of markers related to virulence, i.e., cell-bound hemolysin and production of siderophore aerobactin. 2. No aerobactin-producing strains were found, and the incidence of cell-bound hemolysin was 97%. 3. Hemolysin-positive (58 strains) and hemolysin-negative (2 strains) Serratia marcescens showed the same LD50 (3 x 10(7) bacteria) in a test of virulence for mice. 4. These results indicate that cell-bound hemolysin is not a main factor of virulence for mice in Serratia marcescens. PMID- 1304939 TI - Feeding behavior of different species of Chagas' disease vectors stimulated with blood sources at different temperatures. AB - 1. The feeding behavior of six triatomid species toward latex condoms filled with blood at 26 +/- 1 and 36 +/- 1 degrees C was observed for 4 h. 2. The species studied were Triatoma infestans, Triatoma brasiliensis, Triatoma vitticeps, Triatoma pseudomaculata, Rhodnius prolixus and Panstrongylus megistus, and 34 to 348 insects were studied in each group (average, 190). All the life stages of each species were used. 3. Although most insects (80%, average for 6 species) preferred the warmer blood, 54% of the individuals of all species fed on blood kept at 26 degrees C. For Triatoma pseudomaculata, a higher proportion of insects fed on blood at 26 degrees C (92%) than on blood at 36 degrees C (65%). 4. These results suggest that bait containing insecticides which are effective through the digestive tract may be useful in the control of these vectors even at room temperature. PMID- 1304941 TI - Voluntary intake of "Tiquira", an alcoholic beverage prepared from fermented manioc, decreases immunoglobulin production and increases self-reactivity in mice. AB - We studied the effects of chronic voluntary ingestion of "Tiquira" (50%)--an alcoholic beverage prepared from fermented manioc, widely consumed in Maranhao,- on the natural immunological activity of young adult (2-3 months old) C57B1/6J mice (16-17 g) by evaluating the number of plaque-forming cells (PFCs) in the spleen and by titrating serum antibodies by ELISA. Voluntary ingestion of "Tiquira" for 30 days decreased immunoglobulin secretion in serum ( CONTROL: 1600 +/- 30 vs EXPERIMENTAL: 193 +/- 20), caused an impressive reduction in the total number of PFCs in the spleen ( CONTROL: 482 +/- 22 vs EXPERIMENTAL: 58 +/- 3) and increased the proportion of self-reacting antibody molecules in serum ( CONTROL: 119 +/- 16 vs EXPERIMENTAL: 800 +/- 20) and self-reactive PFCs to mouse red blood cells (MRBC) in the spleen ( CONTROL: 183 +/- 14 vs EXPERIMENTAL: 272 +/- 16; N = 10 animals per group). These preliminary results suggest that the voluntary ingestion of "Tiquira" for 30 days may interfere with immunological relations by decreasing the total number of immunoglobulin secreting cells and increasing the anti-self antibody production. Experiments are in progress to determine if ethanol or other substances present in "Tiquira" are responsible for the effects documented here. PMID- 1304940 TI - Immunoenzymatic quantitation of antibodies to Bothrops asper myotoxins after polyvalent antivenom administration in mice. AB - 1. Two quantitative enzyme-immunoassays (EIA) for Bothrops asper myotoxin and anti-myotoxin antibodies, respectively, were utilized to study their in vivo distribution in mice (Swiss, 18 to 20 g). 2. After polyvalent antivenom (0.4 ml) administration by the iv route, there was an immediate peak in plasma anti myotoxin antibodies which declined rapidly during the first hour, and then decreased more gradually. Anti-myotoxin antibodies were detected in muscular tissue (gastrocnemius) following iv injection of antivenom. After im injection of antivenom (0.4 ml), a slow and steady increase in plasma anti-myotoxin levels was observed, with a peak at 24 h. 3. Mice that received antivenom (0.4 ml) by the iv or im route 15 min after im injection of B. asper venom (100 micrograms) had lower levels of plasma anti-myotoxin antibodies than controls injected with antivenom only, suggesting that at least a fraction of the antibodies combines with myotoxins in vivo. 4. Myotoxin was not detected in plasma at any time after venom injection by the im (100 micrograms) or ip (40 micrograms) route. Following iv injection of 50 micrograms of purified myotoxin II, all plasma samples were also negative, at a detection limit of 10 ng/ml. 5. It was demonstrated that myotoxin II binds to mouse erythrocytes in vitro, a fact that could partially explain its rapid in vivo disappearance from plasma. 6. The present results on the distribution of anti-myotoxin antibodies in vivo are in agreement with previous experimental studies reporting the poor neutralization of myotoxicity induced by B. asper venom when antivenom is injected im, in comparison to i.v. injection. PMID- 1304942 TI - Human leukocyte A and B antigen, gene and haplotype frequencies in the population of the city of Sao Paulo in Brazil. AB - 1. Antigen, gene and haplotype frequencies are important data for population analysis, paternity exclusion testing, genetic studies, and for organ transplantation selection. 2. We have studied the Class I histocompatibility antigens of 617 unrelated individuals from the city of Sao Paulo, Brazil, to determine antigen and gene frequencies of 16 HLA-A and 28 HLA-B antigens. Estimated haplotype frequencies were also determined, as well as the genetic distances of this population from European Caucasian and Negro populations. 3. A previously unknown linkage disequilibrium was detected for A23-B49 and a clear trend towards antigen frequencies intermediate between Caucasoid and Negro populations was observed. PMID- 1304943 TI - Relationship between immune response and clinical manifestations in patients with tuberculosis. AB - Cutaneous reactivity to purified protein derivative (PPD) and antibody levels were investigated in 122 adults and 28 children with tuberculosis. IgG anti-PPD levels (measured by ELISA and reported as absorbance at 405 nm) were higher in adult patients with the disease for more than one year (0.533 +/- 0.391, N = 38 vs 0.224 +/- 0.256, N = 50 in patients with the disease for less than one year) as well as in children with disseminated tuberculosis (0.138 +/- 0.137, N = 11, vs 0.072 +/- 0.055, N = 15 in children with localized disease). The cut-off values (mean + 2SD) for healthy children and adults were 0.09 and 0.22 absorbance at 405 nm. In both adult and pediatric patients, cutaneous reactivity to PPD was inversely correlated with antibody levels. The present data provide additional evidence for the existence of an unstable spectrum of immune response in tuberculosis patients in whom changes in clinical situation are dynamic. PMID- 1304944 TI - Partial characterization of hemagglutinin activity of the marine sponge Anthosigmella varians. AB - The marine sponge Anthosigmella varians contains proteins that agglutinate human erythrocytes irrespective of their ABO group antigens. The hemagglutination reaction depends on divalent cations and is not inhibited by L-arabinose, D xylose, L-rhamnose, D-galactose, D-glucose, L and D-fucose, N-acetyl-D-galac tosamine, N-acetyl-D-glucosamine, methyl-alpha-D-mannopiranoside, D-cellobiose, lactose, maltose, melibiose nor raffinose (33 mM each). A partial purification of the hemagglutinins with 31-fold increase in SA and 80% recovery of activity was obtained after gel filtration and ion-exchange gradient elution chromatography. Hemadsorption experiments carried out with the semipurified fraction using glutaraldehyde-fixed human erythrocytes suggest that proteins with molecular weight of 90 and 34 kDa participate in this reaction. PMID- 1304945 TI - Biocytin as a retrograde tracer in the mammalian visual system. AB - We have successfully used biocytin as a retrograde tracer in the mammalian visual system. Retinal ganglion cells, pyramidal and stellate cortical neurons were labelled. Both pressure injections and gel implants were used successfully for retrograde labelling. Biocytin was detected using avidin conjugates and horseradish peroxidase histochemistry. Retrograde filling with biocytin proved to be more reliable and to allow better morphological resolution than other commonly used neurotracers such as horseradish peroxidase. The fine details of cell morphology observable by this method are comparable in many cases to the results obtained with intracellular tracer injections. The morphological resolution obtained with this method allows the study of brain microcircuits using extracellular deposits of biocytin. PMID- 1304946 TI - Comparison of the anti-inflammatory effects of topically applied aspirin and indomethacin following photocoagulation of the rabbit iris. AB - 1. A comparative study of the inhibitory action of topically applied indomethacin and aspirin (1% (w/v) 2 h before and immediately after trauma, totaling 4 mg each) on myosis, increase in intraocular pressure and breakdown of the blood aqueous barrier was performed. 2. Argon laser photocoagulation on the anterior surface of the left iris of pigmented rabbits, totaling 2,250 mJ, was used as traumatic stimulus. The untraumatized eye was used as a reference for measurements. 3. Four groups of 10 animals each (control, photocoagulated, photocoagulated plus indomethacin and photocoagulated plus aspirin) were studied. 4. Both drugs similarly inhibited the increase in the total protein concentration in aqueous humor and in intraocular pressure at 10, 20 and 40 min. Only aspirin showed some inhibitory action on the pupillary response 10 min after photocoagulation. PMID- 1304948 TI - Effect of estrogens on the adhesion of Trichomonas vaginalis to epithelial cells in vitro. AB - 1. To further characterize the basic aspects of parasite-cell interaction, untreated and hormone-treated Madin-Darby canine kidney (MDCK) cells were allowed to interact with T. vaginalis. 2. Among the six hormones assayed, alpha-estradiol caused MDCK cells to become highly adhesive to T. vaginalis. Increases in parasite adhesion of 83% and 68% were obtained by previous incubation of the epithelial monolayers for 18 h with 1 ng/ml alpha-estradiol and 10 ng/ml 17-beta estradiol, respectively. 3. The estrogenic response of MDCK cells was inhibited by tamoxifen, cycloheximide, puromycin, or 2-deoxy-D-glucose. 4. We conclude that MDCK cells possess receptors for estrogens and that T. vaginalis cytoadherence can be influenced by the hormonal cycle of its host. PMID- 1304949 TI - [A study of nutritional support after burn injuries]. PMID- 1304947 TI - Properties of channels from rat liver gap junction membrane fractions incorporated into planar lipid bilayers. AB - 1. Rat liver membrane fractions highly enriched for gap junctions can be incorporated into planar lipid bilayers exhibiting channel currents with both voltage-dependent and independent components. Voltage dependence, however, is only one of the characteristics of liver gap junction channels. Other features include poor ionic selectivity and sensitivity to calcium, pH, octanol and to some intracellularly applied antibodies. 2. To further test the junctional nature of channels from membrane fractions highly enriched in gap junctions incorporated into lipid bilayers we studied the sensitivity of these channels to uncoupling agents and determined channel selectivity properties. 3. We found the incorporated channels to be insensitive to calcium and octanol, and in most cases to pH in the range of 5-7, suggesting that either these agents do not interact directly with the junctional channels or that the corresponding gating regions are inactivated during the isolation and reconstitution procedures. 4. Attempts to block channel activity using polyclonal and monoclonal connexin 32 antibodies were generally unsuccessful, although one antibody (a monoclonal directed against the carboxy terminus portion of connexin32) blocked channel activity. 5. Selectivity measurements indicated that the incorporated channels were slightly cation selective (PNa = PK > PCl) and were permeable to large ions. 6. These results further support the idea that functional connexin32 gap junction channels are present in channel activity recorded from rat liver junctional membranes incorporated into planar bilayers. PMID- 1304950 TI - [Evaluation of nutritional in 149 severely burned patients]. AB - By means of random sampling we selected 149 cases with over 30% TBSA burn (> 10% full-thickness) for evaluation of nutriment supplementation during treatment. We analysed daily caloric supply, nitrogen balance, amount of blood transfusion, Hb, A/G, transferrin, leukocyte, lymphocyte, IgG, Fn and body weight. The data support our impression that hyperalimentation can promote wound healing and raise the survival rate. PMID- 1304951 TI - [Effects of fat intake on immunomodulation in burned patients]. AB - Since fatty acids influence prostaglandins synthesis, and both fatty acids and prostaglandins modulate immune function, we studied the effects of dietary fats on immunomodulation in severely burned patients. We observed that the administration of fish oil can affect immune response after burns, but a high fat intake seemed to markedly reduce the effect. With lower fat intake, fish oil induced a higher mitogenic response of the lymphocyte to PHA and higher blood IgG level in burned patients. These findings suggest that regulation of dietary lipids may play an important role in nutritional support after burn injury. PMID- 1304953 TI - [Problems in parenteral nutrition and metabolic support for burned patients]. AB - Four problems in parenteral nutrition and metabolic support for burns were discussed in this paper. They were: 1. Estimation of the nutrition requirement, especially energy and protein requirements for burned patients. 2. Selection of the macronutrients for parenteral nutrition with burns. 3. Principles of the prescription of parenteral nutrition. 4. Experiences of parenteral nutrition for burned patients. Because of the safety, effectiveness and convenience, the importance and advantage of peripheral parenteral nutrition were emphasized. Some advances in this field were discussed. PMID- 1304952 TI - [A 5-year interval report on study of burn metabolism and nutrition]. AB - This paper introduces the essential experiences concerning studies of burn metabolism and nutrition in our institute in the past five years. 1. Three new and practical animal models were developed for studying gastro-enteral nutrition in burns. 2. With indirect calorimetry, resting energy expenditure (REE) of 92 burn adult patients were measured and analyzed, and on the basis of which a new formula for calculating nutritional supplement in Chinese burn adults was proposed: kcal/day = 1,000 x M2 (body surface area) + 25 x % TBSA (total burn surface area). 3. Through experimental and clinical studies, it was found that antiouperoxide agents (such as SOD, CAT), tolbutamide, glutamine and Chinese herb decoction Sizunzituang all exhibited modulating effects on postburn metabolism and nutrition, e.g. decreasing catabolism, reducing negative nitrogen balance, stimulating secretion of insulin, enhancing tissue utilization of glucose, maintaining the mass of enteral mucosa and improving functions of viscerae. 4. A new less irritating, simple and easy-to-introduce nasal-enteral nutrition tube was devised, which could pass through the pylorus easily into the duodenum usually within 6hrs without using a stylet. It would be useful in the early postburn enteral nutrition supplementation. PMID- 1304954 TI - [Gastrointestinal dysfunction and peroral nutrition after severe burns]. AB - The patient with severe burns is characterized by a hypermetabolic response, and degree of which is proportional to the magnitude of burns. Major thermal injury is often associated with gastrointestinal dysfunction. Failure to provide adequate caloric intake by both enteral and parenteral routes will results in pronounced weight loss, delayed wound healing, depression of host resistance and cellular dysfunction. We analysed 676 burn patients with TBSA over 50%, and found regular changes in gastrointestinal function with endoscopy and also at autopsy. A new dietary programme is described in the article. PMID- 1304955 TI - [Changes in plasma free amino acid concentration in burned patients with sepsis]. AB - The sequential changes in plasma free amino acid concentration were analyzed and compared in burned patients with sepsis (n = 12) and without sepsis (n = 19). After burn injury, phenylalanine, methionine, lysine, and the Phe/Tyr ratio were significantly increased in two groups (P < 0.05-0.01). Threonine, serine, histidine, arginine, proline and BCAA/AAA ratio were significantly decreased in two groups (P < 0.05-0.001). The Phel Tyr ratio in patients with sepsis was much higher than that in patients without sepsis on postburn days 14 and 21 (P < 0.05), while the BCAA/AAA ratio in patients with sepsis was much lower than that in patients without sepsis on postburn day 14 (P < 0.01). The level of proline in patients with sepsis was much higher than that in patients without sepsis on postburn days 3 and 7 (P < 0.05). It is suggested that these results, in collaboration with other clinical and laboratory findings, may be helpful in foretelling the probable development of sepsis in patients with major burns. PMID- 1304956 TI - [Reverse flow axial island flap in the mastoid region]. AB - Anatomical and clinical studies on the reverse flow axial island flap in the mastoid region were reported. The studies in the dissection of 9 cadavers with a total of 17 sides and the observations in 6 operations proved that the blood in the superfacial temporal artery could flow reversely into the postauricular artery through the anastomotic branches to nourish the mastoid island flap. So the island flap wit a fascia pedicle containing the superficial temporal vessels could be transferred to various region of the face through subcutaneous tunnel to repair deformities of the orbit, nose, eyes and cheek in one stage operation. This reverse axial island flap has been utilized in 18 cases. 16 flaps survived. All cases were followed up for 2 to 7 years. The results were satisfactory. PMID- 1304957 TI - [Island flap with anastomosis of small saphenous vein to great saphenous vein]. AB - We have devised a small saphenous island flap and successfully used in 6 patients for repairing soft tissue defect of the hell and the sole. After its transference, the small saphenous vein was anastomosed to the large saphenous vein over the ankle in order to obtain the blood supply from the small saphenous vein and blood return through the large saphenous vein. The advantage of this flap is that the vessels are superficial with large caliber so that it is easy to do anastomosis without any influence to the donor area. We believe that this flap can be used to repair soft tissue defect of the leg and foot. In this article, the operative method and advantages and shortcoming are introduced. PMID- 1304958 TI - [Clinical application and anatomy of flaps proximal to external malleolus]. PMID- 1304959 TI - [Double island flaps from middle and ring fingers for the repair of soft tissue defects of the thumb (clinical and anatomical studies)]. AB - This article reports the clinical application of double island flaps from the middle and ring fingers for the repair of soft tissue defects of the thumb in 16 cases and the results of the study in applied anatomy with 23 palms from adult cadavers. The double island flaps based on the pedicle of the second digital palmar common artery and the associated digital palmar common nerves have proved to be suitable materials for the repair of the soft tissue defects of the thumb. The method is applicable to the defects of soft tissue distal to the MP joint of the thumb. The repaired thumb is considered to have satisfactory contour and function. PMID- 1304960 TI - [Use of glutaraldehyde preserved allogeneic and xenogeneic cartilage in plastic surgery]. PMID- 1304961 TI - [Monitoring of renal function in burn patients with radioimmunological evaluation]. AB - Urinary beta 2-microglobulin, albumin, IgG, Tamm-Horsfall mucoprotein, and glycoprotein were determined on PBD 0, 1, 3, 7, 14, 21, 27. It was found that the amount of albumin was double that of normal in patients with burn extent of 30% 50% TBSA, while IgG showed no change. In patients with over 50% TBSA burns, Alb was five-fold and IgG four-fold of normal. They probably indicated the degree of damage to the glomeruli. In 27 patients with infection, beta 2-m was increased, indicating damage to the proximal convoluted tubules. Glycoprotein showed a tendency to increase in moderate and severe burns, while it was markedly reduced in very large burns or renal failure, indicating damage to the ascending limb of thick medullary loop. The changes in the amount of urinary protein were more sensitive in reflecting early functional changes of the kidney. PMID- 1304962 TI - [Transplantation of cutaneous nerve from cervical plexus for the early treatment of facial palsy]. PMID- 1304963 TI - [Repair of bedsores and ulcers with gluteus maximus musculocutaneous flap]. AB - From 1984 to 1991, 5 cases of bedsores and 1 case of ulcer resulted from irradiation in gluteal region were repaired with gluteus maximus musculocutaneous flaps. All 5 cases of bedsores were the result of paraplegia. After a myocutaneous flap was transferred, the donor area was directly sutured without skin grafting. The excision wound in one patient reached 18 cm x 12 cm in size, however it was still repaired with total gluteus maximus musculocutaneous flap, and the donor area was also immediately closed with sutures. All of the patients were healed by first intention. For non-paraplegic patients it was deemed contra indicated to use a total maximus gluteus musculocutaneous flap, and instead one half of the muscle was used, in order to avoid impairment of function of the hip joint. PMID- 1304964 TI - [Early fluid therapy for dogs with severe burn-blast combined injury]. AB - Fifty male mongrel dogs were inflicted with 25% III degree burn combined with moderate blast injury. They were divided into five groups; four treatment groups (with various amounts of infused fluid and sodium) and one control group. Each group consisted of 10 animals. The results indicated that every kind of treatment was effective. However, the regime of crystalloid plus whole blood (infused 8 h after injury) was the best. Generally speaking, fluid therapy should be given carefully. The optimal amount of sodium given was 0.3 mmol.kg-1.1%.BSA-1. The amount of water-2-2.5ml.kg-1% BSA-1. After treatment with the Parkland formula, the pulmonary water content was high, so it is not worth recommending. Continuous measurement of the viscosity of plasma, microhematocrit and the amount of sodium in urine and blood were simple and useful. PMID- 1304965 TI - [Changes in the concentration of plasma cardionatrin and morphological changes of atrial cardiocytes after severe burn]. AB - The purpose of this experiment is to investigate the changes in plasma concentration cardionatrin of and morphological changes in atrial cardiocytes in rats after severe burn by means of radioimmunoassay, immunocytochemistry, electron microscopy and morphometry. The results showed that: (1) At 1, 2 h postburn the plasma cardionatrin concentrations were significantly increased, at 6-48 h significantly decreased and at 72, 168 h returned to normal. (2) The changes in plasma cardionatrin concentration were related to the alterations of secretory function in atrial cardiocytes. (3) The pathological changes in atrial cardiocytes were characterized by appearing early. The pathological changes and alterations of secretory function of atrial cardiocytes ran a dynamic course, which could be roughly divided into three phases, the phase of stress, the phase of secretory inhibition and injury, and the phase of recovery. (4) It might be one of the forms of atrial cardiocytes secreting cardionatrin that the atrial specific granules with intact limiting membrane were excreted from the defect of plasmalemma. PMID- 1304966 TI - [Experimental study on monitor of microcirculation of random skin flaps and early division of their pedicles]. AB - In a series of 30 random skin flaps formed in pigs, the skin capillary blood flow was measured with laser doppler flowmetry (LDF) pre-, and postoperatively and within 48 hours after pedicle division. The results showed that the change in the microcirculation can be divided into three phases: (1) rapid rising, (2) plateau, and (3) slow rising. The plateau stage may be considered as the critical period. Division of the flap before this "critical" period causes flap necrosis, while division after the period resulted in flap survival (100 percent). Comparison of preoperative and postoperative LDF values can be regarded as a reliable objective criterion for division of the pedicle. PMID- 1304967 TI - [Calcitonin gene-related peptide and survival of flaps]. PMID- 1304968 TI - The corrosion behavior of Nd2Fe14B and SmCo5 magnets. AB - Rare earth magnets have corrosive problems associated with their use in prostheses in various fields including orthodontics. The purpose of this study is to investigate the corrosion behavior of an Nd2Fe14B magnet and a SmCo5 magnet in an oral environment. The relations among the attractive force changes, the released elements, the weight changes and the anodic polarization measurements of the magnets were examined under immersions in 1% NaCl, 1% lactic acid, 0.05% HCl, 0.1% Na2S and Greenwood's artificial saliva at 37 degrees C for forty-two days. The results showed that the rare earth magnets underwent high corrosive assaults and large attractive force reductions by the immersions in 1% lactic acid and 0.05% HCl. The problem of corrosion of the magnets could be overcome by sealing them within laser-welded stainless steel capsules. PMID- 1304969 TI - Phase transformation of octacalcium phosphate in vivo and in vitro. AB - Octacalcium phosphate (OCP) was implanted in both thigh muscle pouches of ddY mice for 3 weeks, and was soaked in a simulated body fluid (SBF) and 1% NaCl solution maintained at 37 degrees C for 1 day, 1 week and 3 weeks. After implantation or soaking, the specimens were characterized by scanning electron microscopic analyses, X-ray diffractometry, and infrared absorption spectroscopy. X-ray diffraction study showed that OCP had been completely transformed to apatite with low crystallinity such as the mouse's femur after a 3-week implantation in the mouse body, and an apatic crystal was formed after soaking in the NaCl solution. The IR absorption spectra revealed that CO3 was incorporated in the apatite formed from OCP in both the mouse body and the NaCl solution, while OCP changed little after soaking in the SBF. It seems that the magnesium ion retards the transformation of OCP to apatite. PMID- 1304970 TI - A new procedure of the tensile fatigue test for dental materials. AB - A new tensile fatigue test using a stainless steel screw was introduced. A transparent PMMA rod was selected as the test material. A hole was drilled and tapped into the rod; a screw was put into the rod with dental cement or without cementation. Three types of cyclic loads were applied to the test piece; the number of times the load was applied when the initial crack was observed and when the final fracture occurred were recorded. Surface observation showed that actual fatigue fractures occurred in the test piece. The preferred applied load waveform was the cyclic haver-triangles load because of the small coefficient of variance. Fatigue strengths of test pieces with and without cementation were different. Cementation improved the fatigue properties, and the type of cement had an effect on the fatigue properties. Although the number of final fractures minus the number of initial cracks was the constant regardless of the type of cement used. PMID- 1304971 TI - A new method for assessment of marginal sealability of dental restorations. AB - A new testing system was developed for assessment of marginal sealability of dental restorations. It was constructed with a thermocycle loading line and a leakage detecting line partitioned from each other by the restoration under evaluation. The hot and cold solutions of rhodamine B as a tracer were alternately circulated in the thermocycle loading line by the switching of six solenoid valves. Marginal leakage of the tracer into distilled water circulating in the detecting line was periodically monitored by a spectrometer while thermocycling the restoration. The leakage data could be analyzed on the basis of an empirical formula. In application of this method, the durability of a complete seal against thermal changes was estimated on three teeth each of which was restored with an inlay, an amalgam or a glass ionomer. PMID- 1304972 TI - Influence of composition and purity on tensile properties of Ni-Ti alloy castings. AB - The influence of composition and purity of titanium on the mechanical properties and the transformation temperatures of Ni-Ti alloy dental castings was investigated by tensile testing and differential scanning calorimetry (DSC). The compositions of the ingots were 49.0-49.2 at% of titanium content. Three grades of titanium of relatively high purity were used as starting materials. The result showed Ni-49.0Ti to be a somewhat brittle property, and Ni-49.2Ti to have low apparent proof strength and large elongation. Residual strain increased with increasing titanium content. Even small reductions of titanium purity influenced the tensile properties and the transformation temperatures, causing high apparent proof strength, low residual strain and low elongation because of the reduction in transformation temperatures. PMID- 1304973 TI - Compressive creep and recovery of composite resins with various filler contents in water. AB - The compressive creep and the recovery of composites in water were examined. The creep strain of the composites after a 500h test linearly decreased with the increase of their filler content. Their water sorption during testing decreased with the increase of applied stress on the composites containing low filler contents. In the composites containing high filler content, the water sorption was almost constant for some stress levels. The recovery of the composites after testing was significant immediately after testing. From the measurement of the water sorption of the composites, the microcrack or the craze should occur at the filler/matrix interface or in the matrix itself during the creep test, and water could diffuse to the microcrack or the craze after testing in unstressed conditions. This would explain the increase in the water absorbed in the composites in the recovery period. PMID- 1304974 TI - Residual monomer and pendant methacryloyl group in light-cured composite resins. AB - Microareas (100 x 100 microns 2) of thin visible light-cured composite sections irradiated for 10-60 s were analyzed with a Fourier transform infrared spectrometer equipped with a microscopic unit before and after extraction of residual monomers to determine the percent unreacted double bonds (UDB) and percent pendant double bonds (PDB). The percent eluted double bonds (EDB) was calculated using these percents. Analysis was conducted at various depths along the midline from the irradiated surface to the base. There were significant differences among the tested materials at each depth in UDB, PDB and EDB percents. The percent PDB of each material remained almost constant (25-40%) to a certain depth. This depth was equivalent to 70-80% of the depth of cure for each material. The range of depths at which percent PDB was constant indicated greater than 35-40% degree of conversion. At these locations, the composites may polymerize with a high rate of crosslinking. PMID- 1304975 TI - Thermal coefficients of paste-paste type pulp capping cements. AB - Thermal coefficients of four kinds of commercially available paste-paste type pulp capping cements were examined. Control reference samples were made of dentin. A thermal coefficient analyzer was used, heating specimens for a few nanoseconds by a xenon flash bulb and measuring thermal changes by using a thermocouple. Thermal coefficients were examined by this non-steady state method. Thermal conductivities of all cements were almost the same or lower than that of dentin. Therefore, when each cement was heated, the penetrating energy was almost the same or lower than that of dentin. The thickness of the cements was converted into that of the dentin by using the obtained thermal conductivity. The 1-mm thickness of the examined cements were equal to between 0.97-mm and 2.10-mm thicknesses of lost dentin. The use of a pulp capping cement provided better pulp protection from thermal stimuli than did the same thickness of dentin. PMID- 1304976 TI - Improved power control during microwave heating in biological applications. AB - The heating performance of prototype variable power control units attached to two domestic microwave ovens, 500 W and 700 W, was investigated. The units employed the phase control method where rated voltage was obtained by switching AC supply at a particular angular position on the sinusoidal voltage. In order to create experimental conditions employed in a previous study, Sydney tap water (50 mL) was heated at a 10% power level in the 500 W oven. Water boiled at 10 min in both experiments. However, the precision and control of the heating was greatly improved with addition of the control unit. A disinfecting solution (50 mL) and a tissue fixative (10 mL) were included for experiments with the 700 W oven. A power level of only 1% was sufficient to maintain the temperature of the fixative at low temperatures (30-40 degrees C) where many biological reactions occur. The present results indicate that microwave heating power can be controlled by the variable power control method. This will make temperature control possible through the provision of an electronic feedback loop which links a thermocouple with the power control unit. PMID- 1304978 TI - [Challenge to the general internal medicine]. PMID- 1304977 TI - [Retrospect of yesterday, prospect of tomorrow and welcoming the new advances: celebration to the 40th anniversary of the Chinese Journal of Internal Medicine]. PMID- 1304979 TI - [Brief history of the Chinese Journal of Internal Medicine]. PMID- 1304980 TI - [Recent advances and prospect of infectious diseases in China]. PMID- 1304981 TI - [Prevention and treatment of parasitoses: a prospect and analysis of the recent state]. PMID- 1304983 TI - [Achievements in prevention and treatment of respiratory diseases]. PMID- 1304982 TI - [Advances in cardiovascular diseases in recent 10 years]. PMID- 1304984 TI - [Achievements in the research on digestive diseases]. PMID- 1304985 TI - [Advances in hematology in recent 40 years]. PMID- 1304986 TI - [Development of nephrology in the past decade]. PMID- 1304987 TI - [Advances in endocrinology in recent 10 years]. PMID- 1304988 TI - [The founding and developing of rheumatology in China]. PMID- 1304989 TI - [Main advances in neuropsychiatry in recent 10 years]. PMID- 1304990 TI - [An analysis of the references in the Chinese Journal of Internal Medicine]. PMID- 1304991 TI - [The preliminary study of monoamine oxidase activity in platelets in patients with schizophrenia and affective disorder]. AB - This paper has studied the MAO activity in platelets of 52 schizophrenic patients and 44 affective disorder patients. The results indicate that the MAO activity in platelets of schizophrenic patients is lower than that of normal group, especially the chronic schizophrenic patients. It's no difference between the acute schizophrenic patients and normal group. The MAO activity in platelets of bipolar affective disorder patients is much lower than that of normal group. Platelet MAO activity in male bipolar affective disorder is lower than that of female's, that of bipolar-manic effective disorder is lower than that of bipolar depressive effective disorder. The MAO activity in platelets of unipolar depression is even lower than that of normal group. PMID- 1304992 TI - [A double-blind study of metoclopramide in the treatment of schizophrenia and determination of prolactin]. AB - This paper reported that 40 schizophrenic patients treated with metoclopramide and haloperidol respectively with double blind observation. Dosage of these two drugs were 450 = 133 mg and 32 +/- 9.2 mg everyday respectively. The effect of metoclopramide were that: 67.5% (27/40) of patients had marked improvement and 85% (34/40) improvement. And the effect of haloperidol were 65% (26/40) and 80% (32/40) respectively. Both of these two drugs had no significant difference. Their main side effect was extrapyramidal reaction, and metoclopramide was milder in this. Detecting serum prolactin before and after treatment in 6 cases of metoclopramide therapy and 5 cases of haloperidol therapy. The ratio of serum levels of prolactin before and after treatment was 3.58 and 4.86 in both drugs therapy respectively. PMID- 1304993 TI - [A control study on memory and related factors in patients with depression]. AB - The results of an analysis of memory function and related factors in 107 patients with depression and in 76 normal controls revealed that obvious disturbance of memory level and various functions including long-term memory, short-term memory and immediate memory, were seen in observation group. The disturbance of memory function was related to sex, age, education and occupation. No relationship in EGG and depression was found. PMID- 1304994 TI - [Application of ischemic score of Hachinski in differentiation of multi-infarct dementia]. AB - The Beijing Geriatric Mental Health Center has admitted 46 cases of dementia of the aged in recent more than two years. For them many routine examinations as well as rating scale related and CT scanning were carried out. Their final diagnosis at discharge were of 4 categories: (1) Multi-infarct dementia (MID); (2) Alzheimer's disease(AD); (3) MID+AD, mixed type; and (4) dementia of other causes. We applied Ischemic Score of Hachinski for the 14 cases of MID. The score was over 7 points in all the 14 cases. And the CT pictures in 11 cases showed multiple infarctions, only 3 cases gave evidence of cerebral atrophy. Therefore, the Ischemic Score and CT Scanning were very significant in the diagnosis of MID. The role of each item of the total 13 items of the ischemic score in the diagnosis of MID was discussed according to the clinical materials. It is pointed out that the "stepwise deterioration", "fluctuating course", "history of strokes" and "focal neurological signs" were more important in the diagnosis of MID. PMID- 1304995 TI - [Clinical analysis of senile and non-senile affective psychosis]. AB - This article analysed 101 cases of affective psychosis in accordance with CCMD-2 diagnosis criteria. There were 42 cases over and 59 under 60 in age. The results indicated that the patients of the senile affective psychotics accounted for 30.47% of the hospitalized psychotics in the same time. 78.57% of the old group were psychically and somatically precipitated. The proportion was much higher than the non-senile. The degree of the senile group was much higher than the non senile in manic attack, while it was much lower in depressive attack. The dosages and the plasma level of Li in the former were markedly decreased in comparison to the latter group. PMID- 1304996 TI - [A clinical and follow-up study in 33 cases of rapid cyclic affective psychosis]. AB - Three hundred and fifty one cases of manic-depressive psychosis in our hospital were reviewed. Of these, 33 cases were rapid cyclothymic type (9.4%). Their clinical features, including sex, age, personality characteristics, phenomena and clinical types were analysed. The results suggested that: the major precipitating factors are psychosocial factors and antidepressants; the better therapy is the administration of the lithium combined with carbamazepine or neuroleptics; and more ideal prognosis occurs in any patient persisting in receiving the therapy. PMID- 1304997 TI - [The study of occurrence mechanism in acute and chronic cerebral vasospasm]. AB - Using radioimmunoassay, fluorescence and transmittal++ electronmicroscopy, we studied the of prostaglandin(PG), lipid peroxidation(LPO) and ultrastructure. Fresh arterial blood (imaging acute spasm) produced basilar arterial spasm strongly(+ + +) and vacuole deterioration in vascular walls but there were no changes in 6-keto-PGF1 alpha and TXB2 and PGE2 and LPO. Incubated arterial blood (imaging chronic spasm) produced basilar arterial spasm markedly (+ + +) also. Vacuole deterioration in vascular walls either, and decreased the level of 6-keto PGF1 alpha apparently (P < 0.01) and elevated the content of LPO significantly (P < 0.01) and there were no changes in the level of TXB2 and PGE alpha. This experiment suggests that the mechanism of acute spasm and chronic spasm is different. PMID- 1304998 TI - [Changes in gerbil brain tissue following cerebral ischemia and postischemic reperfusion and studies of the effects of the Chinese drugs]. AB - With the animal model of cerebral ischemia and reperfusion, we conducted experiments on such model to study the effects of Ligustrazine(LZ) and Salvia Miltirrhizae(SM). The results obtained are as follows: (1) The ischemic brain showed hyperperfusion (congestion period) after 10 min reperfusion following 50 min of ischemia, and then entered a delayed hypoperfusion period after 60 minutes reperfusion and afterward the hypoperfusion was remained till the end of 120 min reperfusion. (2) Following 50 min of ischemic insult, ATP and glucose contents in brain tissue were almost depleted and much of lactate accumulated. Although rapid recovery of energy metabolism occurred within 60 min of reperfusion, a secondary deterioration emerged at 120 min of reperfusion. (3) Apparent brain edema occurred after cerebral ischemia and its further development was observed at the early stage of reperfusion owing to congestive response. Despite the degree of brain edema alleviated obviously after 60 min of reperfusion, the condition become worse at 120 min of reperfusion, which was accompanied by secondary metabolic deterioration. (4) Experimental results showed that LZ and SM could significantly elevate rCBF during the delayed hypoperfusion period, and limit the development of secondary deterioration in energy metabolism and brain edema after 120 min of reperfusion. (5) Notably, LZ and SM had no significant effect on MABP when these two Chinese drugs manifested their therapeutic actions in the animal model of cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1304999 TI - [A study on the activity of three antioxidant enzymes in the brain of experimental acute cerebral ischemia]. AB - The activities of Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px) and Catalase (CAT) in the ischemic cerebral tissue following the unilateral middle cerebral artery occlusion of rats were assessed. In comparison with the sham operated rats, both SOD and GSH-Px activity in the ischemic area (striatum and fronto-parietal cortex) were significantly reduced by 30 min. of ischemia, GSH-Px activity in the peri-ischemic area (parieto-parasagittal) was significantly reduced as well. It was shown that in the striatum the GSH-Px activity was much higher than that in the cortex. According to our data, it was suggested that in the ischemic condition, cerebral Superoxide (O2-) and Hydrogen Peroxide (H2O2) were accumulated, and thus the polyunsaturated fatty acids in the neuronal membrane were trapped by these free radical. And such a process resulted in neuronal damage. It implicated that the oxygen free radical might be involved in the neuronal damage induced by Dopamine, since the O2- and H2O2 were excessively generated during the oxidative deamination of Dopamine and the free radical scavengers, SOD and GSH-Px were decreased concomitantly in the cerebral ischemic tissue. PMID- 1305000 TI - [Treatment of experimental ischemic cerebral lactic acidosis in rats with dichloroacetate]. AB - In the cerebral ischemic pathophysiologic mechanism, lactic acidosis is a important factor to exacerbate cerebral damage. Our research showed that the lactic level of cerebral cortex in rats increased rapidly after the focal cerebral ischemia or during blood reperfusion after cerebral ischemia, 26.99 +/- 5.89 and 28.63 +/- 5.08 mumol/g brain wight respectively, it exacerbated significantly brain edema and pathological damage. The lactic level decreased rapidly to treat with dichloroacetate (50 mg/kg body weight) after cerebral ischemia or during blood reperfusion, 14.11 +/- 2.06 and 13.23 +/- 1.71 mumol/g brain wight respectively, brain edema and pathology improved significantly. It suggested that dichloroacetate might across blood-brain barrier into the cerebral ischemic region and lowered lactic level, improved brain internal environment, relieved cerebral damage after focal cerebral ischemia or during blood reperfusion. It may improve the prognosis of patient with ischemic cerebral vascular disease to be treated with dichloroacetate early. PMID- 1305001 TI - [Research on myasthenia gravis in children with HLA supratype]. AB - 38 cases of MG Children's patients were typed for HLA-I, II and III antigens. It shows that MG significantly associated with HLA-A2, Bw46 and DRw9. Their relative risk were 3.60, 8.18. 4.60, Pc < 0.05 or 0.001 respectively. The association with C4 and Bf were not found. Aw19 is seemed as a protection factor of this disease. These results are similar with the research on Chinese MG patients in Hong Kong but are quite different with those of caucasian data. PMID- 1305002 TI - [Clinical analysis of 30 cases of stiff-man syndrome]. AB - Thirty cases of SMS, including 22 cases reported previously in China, were analysed clinically manifested by involvement of neck and facial muscles, slurred speech, dysphagia or dyspnea, exaggerated tendon reflexes, ankle clonus and/or Hoffmann's sign. Half of them had past history of infection. Five out of 18 CSF examined showed elevation of protein content, immunoglobulin and white cell count, suggesting the presence of inflammation or demyelination changes in CNS. The pathology of the syndrome is probably located in the spinal cord or brain stem. The criteria for diagnosis are proposed. For treatment, the dosage and way of administration of diazepam should be judged according to the severeness of the disease; nitrazepam and clonazepam are effective, too. PMID- 1305003 TI - [A study of the P300 cognitive potential on mental deficiency in children]. AB - The study of 36 cases of P300 Cognitive Potential (P300 CP) of mental deficiency children have been made. The results of examination were abnormal in 31 cases (85%). In the 31 cases the latency of P300 the cognitive waves (P300 CW) were prolonged, the amplitude were reduced and the P300 CW disordered. After discussion of the relation among the P300 CW, the intelligence quotient (IQ) and the EEG, it were pointed out that P300 CP is as sensitive, objective, valuable indexes for checking and testing intelligence of mental deficiency children. PMID- 1305004 TI - [Advances in the research on the pathogenic role of Campylobacter jejuni in Guillain-Barre syndrome]. PMID- 1305005 TI - Aging in America. PMID- 1305006 TI - Dentistry and the chemically dependent patient. PMID- 1305007 TI - Overview: infectious disease policies. PMID- 1305008 TI - Exophytic hard tissue mass: a case report. PMID- 1305009 TI - Practice development: where do you go from here? PMID- 1305010 TI - A question of obligation. PMID- 1305011 TI - Proceedings of the 186th meeting of the Netherlands Ophthalmological Society. Maastricht, the Netherlands, June 1992. PMID- 1305012 TI - Comparison between postoperative astigmatism after classic extracapsular lens extraction and after phacoemulsification with implantation of a Pearce tripod or Pearce vaulted Y-loop intraocular lens. AB - We compared the surgically induced astigmatism after standard extracapsular cataract extraction (ECCE) with the astigmatism following cataract extraction by phacoemulsification. The surgically induced corneal astigmatism was assessed on several occasions, ranging from one day to one year postoperatively. After phacoemulsification, this astigmatism was considerably slighter than after ECCE on day 1 postoperatively and after two and six weeks. However, one year postoperatively, this difference was less clear. We then measured slight against the-rule astigmatism for both surgical techniques. PMID- 1305013 TI - Recurrent hemangiopericytoma and brachytherapy. AB - A 42-year-old woman had two recurrences following excision of a hemangiopericytoma of the left orbit. A third local excision was followed by postoperative brachytherapy (55 Gy in 100 hours). One year later there is no sign of recurrence and the side-effects are minimal. PMID- 1305014 TI - Pseudophakic endophthalmitis. AB - We performed a retrospective study on 45 patients admitted to the Rotterdam Eye Hospital and the Ophthalmic Department of the Academic Medical Center in Amsterdam with pseudophakic endophthalmitis. Vitreous loss during cataract extraction was associated with a significantly increased risk of postoperative endophthalmitis when compared with uncomplicated cataract extraction (p < 0.0001). The incidence of pseudophakic endophthalmitis in diabetic patients was not significantly higher as compared to non-diabetic patients. Vitrectomy in the treatment of postoperative endophthalmitis did not improve the final visual acuity, probably because of selection bias. Methicillin and cephazolin, used intravitreally against gram-positive organisms, failed to provide a good coverage for endophthalmitis due to Staphylococcus epidermidis. PMID- 1305015 TI - Endophthalmitis: incidence, therapy and visual outcome in the period 1983-1992 in the Rotterdam Eye Hospital. AB - From 1983 to 1992, 134 patients were treated for clinically suspected endophthalmitis. 61% of this endophthalmitis population consisted of cases that were referred to our clinic. In this nine year period antibiotic treatment was carried out according to three consecutively used guidelines. These three treatment schemes differed in antibiotic spectrum and mode of antibiotic delivery. In 68 patients we performed vitrectomy on account of clinical deterioration under antibiotic treatment. We did not find significant differences in visual outcome between the three treatment groups. The incidence of endophthalmitis following cataract or vitreous surgery did not change throughout the study period. There was however a dramatic decrease in incidence of post traumatic endophthalmitis following the introduction of a prophylactic antibiotic treatment scheme consisting of fortified gentamicin and cefazolin eyedrops, and intravenously and subconjunctivally administered gentamicin, cefazolin, and clindamycin. In 55 of 68 cases in which vitrectomy was performed in conjunction with intravitreal antibiotics, a vitreous or anterior chamber specimen was cultured. 36 patients had a positive culture result. In the group with positive culture result 42% had better visual acuity in the post-treatment period than before treatment. In the group with a sterile culture result 79% had better vision after treatment. PMID- 1305016 TI - (An)aerobic bacteria found in secondary-cataract material. A SEM/TEM study. AB - Twenty four patients, who had marked reduction of vision due to secondary cataract developed after an ECCE, were treated by surgical cleaning of the posterior lens capsule. During this procedure globular secondary-cataract material was removed and collected for morphological examination by SEM and TEM. Fragments of various sizes and shapes, including some with a 'golf ball' structure, were seen; these closely resembled particles frequently found in cataractous lenses. In addition, in 18 patients micro-organisms were found: rod shaped bacteria, cocci, and in 2 cases yeasts. These findings were the more remarkable because these were clinically quiet eyes with no signs of intra-ocular inflammation and cultures have been persistently negative. We imagine that these bacteria must have entered the eye during the cataract extraction and have settled there without causing an infection. PMID- 1305017 TI - Discrepancies between single stimulus and multiple stimulus visual field examinations with the Peritest semi-automated perimeter in glaucoma patients. AB - In a total of 24 randomly selected eyes of glaucoma patients, tested with the automated (single stimulus) and the manual (multiple stimulus) modes of the semi automated Peritest perimeter, the numbers and depths of defects were compared as estimated with these two different measurement strategies. It was found that with the manual technique considerably less defects were detected than with the automated strategy. PMID- 1305018 TI - Serotonin (5-HT) and the rat's eye. Some pilot studies. AB - Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic amine which has a multitude of more or less clearly established effects on peripheral vessels. It influences blood viscosity, platelet aggregation, and vasoconstruction and -dilatation, it enhances capillary permeability, it is the precursor of melatonin (a hormone with diurnal production in the eye). Because of these actions a role for serotonin in the development of glaucoma and diabetic retinopathy might be suspected. In a series of pilot studies on rats the effects of serotonin on the anterior and posterior segments of the eye were studied. Serotonin had marked influence on the retinal and choroidal vasculature. The optic disk seemed to be very sensitive to serotonin. Possibly it had an influence on the blood-retinal barrier. It caused transient cataracts, probably by decreasing the production of aqueous. It blocked tropicamin-induced mydriasis. The techniques and provisional results of measurement of serotonin in human aqueous are also described. PMID- 1305020 TI - Study of the substructure of the Morgagni and Brunescens cataract with the TAO non-coating technique. Part 1: Morgagni cataract. AB - Lens tissue from a Morgagni cataract was examined by SEM and TEM. For SEM, after prefixation with glutaraldehyde and postfixation with the tannic acid/arginine/OsO4 non-coating (TAO) technique, and for TEM, after prefixation with glutaraldehyde, postfixation with OsO4/K4Fe(CN)6 and poststaining with uranyl acetate/lead citrate. The TAO technique seems to be a particularly suitable postfixation method for the SEM investigation of cataract tissue because of the presence of the protein structures present. The cortical region showed areas of radially, instead of concentrically, arranged lens fibres, degenerated lens fibres with holes (vacuoles), broken ball and socket connections between the lens fibres, and oval or spherical structures varying in size from 0.5-20 microns, the largest resembling a golfball, arising from the cytoplasm of degenerating lens fibres. The smallest, 0.2-0.5 microns, appear to have been expelled from the furrowed lens epithelium. PMID- 1305019 TI - The Visual Advice Centre, Eindhoven, The Netherlands. An intervenient evaluation. AB - On referral by ophthalmologists, the Visual Advice Centre provides the partially sighted with advice and prescriptions for illumination and visual aids. In this paper the multidisciplinary structure of the centre is presented and the results obtained in the first 18 months of its existence are discussed. Two hundred and ninety-eight patients were referred to the centre in this period. The majority of these patients (79.2%) were older than 60 years. The main cause of visual impairment was macular disease (45.3% of the patients). An interesting finding is that, although reading is an important need, reading problems only constituted 35.9% of the total number of demands for help. From an inquiry into the situation of 125 patients 6 months after prescription, it appears that more than 90% of the aids prescribed are used regularly. The conclusion is drawn that patients referred to the Visual Advice Centre benefit from the multi-disciplinary approach to their problems. PMID- 1305021 TI - Study of the substructure of the Morgagni and Brunescens cataract with the TAO non-coating technique. Part 2: Brunescens cataract. AB - Lens tissue from a Brunescens cataract was prepared for SEM study by prefixation with glutaraldehyde and postfixation with the tannic acid/arginine/OsO4 combination; for TEM study the material was prefixed with glutaraldehyde, postfixed with OsO4/K4Fe(CN)6 and poststained with uranyl acetate/lead citrate. At low magnification, in contrast to the Morgagni cataract, no difference could be seen between the lens fibres in the cortical and nuclear areas. Morphologically, the destruction of the ball and socket system and the development of holes and spherical structures was striking. The latter appeared to have a thin coating and, after fracture, were either empty or showed remnants of material resembling membranes. In sections of the cataractous material, larger vacuoles containing smaller spheres were indistinctly visible. PMID- 1305022 TI - Comparative anatomy of the vitreous body in rhesus monkeys and man. AB - In the isolated unfixed vitreous body a structural organization can be visualized by slitlamp microscopy or by an ink-injection technique. We discuss the observations on human and rhesus monkey (Macaca mulatta) vitreous bodies using the ink-injection technique. Advantages and disadvantages of this method compared with slitlamp microscopy are described. Eventual functional implications of vitreal organization are mentioned briefly. PMID- 1305023 TI - An analysis of colour vision in 10,000 patients. AB - Examination of a great number of patients resulted in the depth localisation theory. The combination of this theory with the fixation-eccentrisation theory is clinically useful: acquired colour vision defects can be subdivided by the fixation mode and by signs of receptor damage. There are indications that in multiple sclerosis the slowly progressive cases present with more receptor damage than the acute cases. PMID- 1305024 TI - Ocular lubricants and intraocular stray light. AB - The question was raised whether ocular lubricants or artificial tears might have adverse effects on optical clarity of the eye. Eight current commercial products were tested on five young subjects, using the Straylight Meter. No adverse effects were found. PMID- 1305025 TI - Towards a classification of visual impairment. AB - For the rehabilitation of people with impaired vision, it is essential to have adequate (preferably quantitative) information about their residual visual functions. Special attention is given to the extra information provided by the results of measurement of the contrast sensitivity, especially in combination with the results of other measurements, such as the visual field, the amount of intraocular straylight and the visual acuity. The value of the contrast sensitivity function as a predictor of the extent of dysfunctioning in the visual activities of everyday life, such as outdoor vision, reading and recognition of faces, will be discussed. As far as this is concerned, a comparison is made between the value of visual acuity and contrast sensitivity as measures of the extent of vision and visual dysfunctioning. PMID- 1305027 TI - Iris nevi and melanomas: a clinical follow-up study. AB - A follow-up study of 113 patients with suspicious iris nevi who were referred to our clinic between 1973 and 1991 was carried out by: reviewing their clinical records, fluorescein angiography, obtaining recent data with cooperation of their own or the referring ophthalmologist and contacting patients for reexamination. After examination the diagnoses were: 64 suspicious nevi, 23 melanomas, 15 ciliary body tumors with iris involvement and 11 other pseudomelanomas. In the group of suspicious nevi 86% was localized in the inferior part and 66% in the temporal part of the iris; for the melanoma group these figures were 78% and 75% respectively. The chamber angle was more often involved in the melanoma group, 40% against 17% in the suspicious nevi group. In this group 11 cases (21.6%) showed growth during the follow-up (mean 10.6 years). In three cases the tumor was surgically removed, with as histopathologic diagnosis: 1 xanthogranuloma, 1 neurolemmoma and 1 possible melanoma. In the melanoma group 16 lesions (76%) showed growth during the follow-up (mean 7.2 years), in most cases within 5 years of the initial diagnosis. The lesion was surgically removed in 11 cases. The histopathologic diagnoses were: 8 melanomas, 1 xanthogranuloma, 1 possible melanoma and 1 metastasis of a skin melanoma. Our study shows that periodic ophthalmic check-ups are of great importance in the management of iris lesions suspect for melanoma. PMID- 1305026 TI - Possible relation between HLA and ABO type and prognosis of uveal melanoma. AB - Not only local parameters but also genetic determinants like the HLA genes may play a role in the development and clinical behavior of malignant tumors. In skin melanoma the presence of HLA-B40 is associated with a poor prognosis. We tested the hypothesis that the clinical behavior of uveal melanoma is influenced by the HLA type of the patient. The HLA types of 44 patients with uveal melanoma had been determined before operation with a view to using the cornea of the enucleated eye for an HLA-matched corneal transplantation. We compared the ABO and HLA types of the patients with the development of metastases and with the ten year patient survival. An association was observed between the presence of HLA B40 and death due to metastasis of uveal melanoma. We conclude that the HLA type of the patient may influence the clinical behavior not only of skin melanoma but also of uveal melanoma. PMID- 1305028 TI - Analysis of the electroretinogram in toxoplasma retinochorioiditis. AB - The decision to use therapy in toxoplasma retinochorioiditis depends on the location of the active lesion and the presence of vitreous activity. In eyes with dense vitreous clouding it can be difficult to see whether the macular region is involved or not. In theory the localisation of a lesion can be estimated on the basis of the flash ERG. The standard flash electroretinogram was recorded in 23 patients with inactive toxoplasma retinochorioiditis lesions in the retina. In 17 cases a lesion was present within the central 12 degrees of the visual field, 8 of these had a reduced photopic ERG. In 15 patients lesions were found outside the central 12 degrees, in 8 of whom the scotopic ERG was reduced. We conclude that the ERG can be of use in indicating the scar location in patients with dense vitreous clouding. PMID- 1305029 TI - Late consecutive exodeviations. AB - A retrospective study was made of the case-histories of 48 patients with late consecutive exodeviations, which had occurred after surgical treatment of a primary convergent squint. An evident predisposition towards the late appearance of the exodeviation could not be demonstrated. In some cases there seemed directly to have been a slight overcorrection, within the limits of operative success. In spite of the attempted overcorrection in a second operation on account of 'exodrift', recurrence of the exodeviation often occurs. PMID- 1305030 TI - Kearns-Sayre's syndrome developing in a boy who survived pearson's syndrome caused by mitochondrial DNA deletion. AB - A 7-year-old boy presented with bilateral ptosis and atypical retinitis pigmentosa. Before age two, he had had an Fe-refractory anemia, with neutropenia and thrombopenia. Just prior to the ophthalmic examination, the patient developed lactate acidosis, muscular hypotonia, ataxia and increased protein in the spinal fluid. Pancytopenia, pancreas dysfunction and growth retardation are the main features of Pearson's syndrome, most children not surviving beyond age three. The cause of Pearson's syndrome in our patient turned out to be a 5 kb deletion in the mitochondrial DNA. Similar deletions have been described in the Kearns-Sayre syndrome. It seems that children who survive the initial phase of Pearson's syndrome, may develop Kearns-Sayre syndrome. PMID- 1305031 TI - Costs and methods of preventive visual screening and the relation between esotropia and increasing hypermetropia. AB - Atkinson has shown that early correction of hypermetropia reduces the incidence of esotropia. If esotropia is reduced by prescribing glasses early, the rate of esotropia-induced amblyopia can be similarly reduced; this would have important economic consequences. We have studied (1) how costs compare to benefits in early visual screening, (2) how videorefraction as used by Atkinson compares to retinoscopy, and (3) whether esotropia is more likely to occur in children who have increasing as opposed to decreasing hypermetropia. The costs of the study so far have been high. It was exceedingly difficult to get all infants invited, come to the clinic and examined. Videorefraction did not compare favourably with retinoscopy in terms of costs and precision, whereas the amount of skill and time needed was approximately equal. The third question, whether esotropia is more likely to occur in children who have increasing as opposed to decreasing hypermetropia, arose from the controversy whether, in the general population, refraction increases or decreases during the first years of life. We found that papers reporting a decrease of hypermetropia in early childhood were studies of large cross-sections of the general population, whereas papers that reported an initial increase originated from ophthalmological practices or strabismus departments. These conflicting results could be reconciled by assuming a population bias: if esotropia is more likely to occur in children with increasing hypermetropia, children with increasing hypermetropia will preferentially be seen by ophthalmologists. It seems natural that children with increasing hypermetropia are more likely to squint, because additional accommodation, needed to overcome increasing hypermetropia, will inevitably confer additional convergence. This relationship has meanwhile been confirmed by others. PMID- 1305032 TI - Mersilene (polyester), a new suture for penetrating keratoplasty. AB - Mersilene (polyester monofilament) seems to be suitable for penetrating keratoplasty because it is strong, shows no degradation by ultraviolet light, is insoluble, so that it can be left in situ, and offers the possibility of regulating postoperative astigmatism by suture adjustment. In 12 patients penetrating keratoplasty was performed with the combined interrupted/running suturing technique, using eight interrupted nylon 10-0 sutures and one running Mersilene 11-0 suture. The results were compared with those of 25 patients in whom eight interrupted nylon 10-0 sutures and one running nylon 11-0 suture were used. Six months after penetrating keratoplasty, no differences could be found between the two groups in keratometric astigmatism, visual acuity or slitlamp findings. In three patients postoperative adjustment of the running Mersilene suture reduced astigmatism by 50, 90 and 100% respectively. In an animal study the behaviour of Mersilene in the cornea was evaluated by slitlamp examination, histology and electron-microscopy. The tissue response to Mersilene was minimal. Considering the resemblance to nylon in clinical findings, minimal tissue response, lack of biodegradation and possibility of regulating postoperative astigmatism by suture adjustment, Mersilene seems to be a suitable material for penetrating keratoplasty. PMID- 1305033 TI - The determination of the central static visual acuity. AB - In identical experimental situations we tested 22 adults with our proposed Landolt C wall-chart and the so-called TNO Landolt-C chart. Contrary to theoretical expectations, it appeared that there was only a slight difference in the measured visual acuities. Further study will show whether this is an incidental or a structural occurrence. PMID- 1305034 TI - Selective inhibition of in vitro cell growth by the anti-tumour drug Ukrain. AB - The inhibitory effect of Ukrain on malignant cells and on normal cells, in vitro, has been compared. To obtain a 50% inhibition of cell growth, a tenfold concentration had to be used with normal endothelial cells compared to a human osteosarcoma cell line. Hybrids of the two cell types showed nearly the same sensitivity as normal cells. A laser scanning microscope showed a high uptake of Ukrain in malignant cells, while the content in normal cells under the same experimental conditions was substantially lower. PMID- 1305035 TI - Modification of antinociceptive action of morphine by Ukrain in rodents. AB - Morphine-induced (0.1 mg/kg s.c.)antinociceptive action was determined in rodents by using the writhing syndrome, hot plate and tail-flick tests. Ukrain given i.p. in doses equivalent to 0.05 and 0.1 LD50 did not affect the reactivity of the mice in the writhing syndrome test. Only in a dose of 0.1 LD50 did Ukrain produce an antinociceptive effect in the hot-plate and tail-flick tests. Ukrain significantly enhanced the antinociceptive effect of morphine in the hot-plate and tail-flick tests. The action of morphine was significantly suppressed by Ukrain in the writhing syndrome test in mice. These results indicated that Ukrain modified the antinociceptive action of morphine. PMID- 1305036 TI - Effect of Ukrain on the efficacy of anti-epileptic drugs against maximal electroshock-induced seizures in mice. AB - It has been found that Ukrain, given intraperitoneally (i.p.), did not influence the threshold for maximal electroconvulsions in mice. Ukrain in doses of 9.5 and 19 mg/kg significantly enhanced the protective efficacy of valproate, decreasing the ED50 values. However, Ukrain had no effect on the protection provided by diazepam, carbamazepine, diphenylhydantoin and phenobarbital. The combined treatment with Ukrain and anti-epileptic drugs did not cause any signs of toxicity. PMID- 1305038 TI - In vitro effects of Chelidonium majus L. alkaloid thiophosphoric acid conjugates (Ukrain) on the phenotype of normal human lymphocytes. AB - Several plant-derived drugs are used in medical oncology (1-3). The thiophosphoric acid-alkaloid derivative from the plant Chelidonium majus L. (Ukrain) has been produced since 1978 by Nowicky. (Austrian Patent No. 354644, Vienna, 25 January 1980). It has been reported that this drug may exert therapeutic effects in cancer patients by modulating their immune systems (4, 5 8). The aim of this study was to evaluate in vitro the possibility that Ukrain may influence the phenotype of lymphocyte subpopulations isolated from healthy donors. PMID- 1305037 TI - Studies concerning the effect of Ukrain in vivo and in vitro. AB - Ukrain, a reaction product of different alkaloids of Chelidonium majus L. (celandine) with Thio tepa has been investigated for possible use as an anticancer agent. A possible tumour inhibiting effect on the Ehrlich mouse ascites tumour is now tested in vivo. Moreover, possible changes in the oxygen consumption of mouse ascites tumour cells and a guinea pig liver homogenate are to be determined after the administration of Ukrain in vitro with the aid of an oxygen electrode. PMID- 1305039 TI - Teratological evaluation of Ukrain in hamsters and rats. AB - The compound Ukrain, containing thiophosphoric acid alkaloid derivatives from the plant Chelidonium majus L., was given intramusculary (i.m.) on days 6-11 of gestation to hamsters and on days 6-15 of gestation to rats in doses of 0.1, 1.67 and 28 mg/kg daily. No clinical signs of toxicity were found in treated animals and no teratogenic effect could be noted in either species. Such parameters as the number of corpora lutea, implantation sites, pre and post-implantation losses, number of live foetuses per litter, placental weight, foetal weight and crown-rump length were not significantly different between the Ukrain treated rats and the controls. Slight embryotoxic effects (increased post-implantation losses) and in consequence decreased number of average litter size were noted in hamsters exposed to Ukrain at doses which were otherwise not embryotoxic to rats. PMID- 1305040 TI - Evaluation of mutagenic, genotoxic and transforming properties of Ukrain. AB - Evaluation of mutagenic and genotoxic properties of Ukrain was on the basis of the Ames and micronucleus tests. Ukrain was investigated for its ability to induce morphological transformation of embryonic cells of the Syrian hamster. Under the experimental condition used in this study, Ukrain was found to be non mutagenic and non-genotoxic, and furthermore did not induce morphological cell transformation. PMID- 1305041 TI - The immunomodulating preparation Ukrain does not induce anaphylactic sensitization in mice and guinea pigs. AB - The ability of Chelidonium majus L. alkaloids derivative Ukrain to induce an anaphylactic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera, and IgG1a, IgG1b as well as IgE antibody levels in guinea pig sera, were evaluated by passive cutaneous anaphylaxis (PCA) tests. Ukrain alone or adsorbed on aluminium hydroxide gel (alum) introduced into BALB/c mice in several subcutaneous injections was unable to stimulate measurable anti Ukrain IgE antibody response. Moreover, Ukrain introduced together with ovalbumin (OA) into mice in the course of immunization with OA induced lower anti-OA antibody response as compared to the response induced by OA alone. Ukrain adsorbed on alum and injected subcutaneously into guinea pigs did not induce measurable IgG1a, IgG1b and IgE antibody response. The present results suggest that the immunomodulating preparation Ukrain could be therapeutically safe at least as far its inability to induce anaphylaxis is concerned. PMID- 1305042 TI - Clinical studies of Ukrain in healthy volunteers (phase 1). AB - Phase I of a clinical study of Ukrain was performed in 19 healthy outpatient volunteers. Their general clinical conditions were evaluated, as well as the following parameters: biochemical, haematological, immunological, electrolyte and trace elements, neopterin, immune complexes and non specific blocking factors. Ukrain was administered intramuscularly (i.m.) or intravenously (i.v.) every one, two or three days in doses of 5 to 50 mg for 7 to 40 days. In one case the drug was administered for three years in the dose of 5 to 50 mg/injection in repeated courses. During the investigation no significant changes were found in clinical states. During the intramuscular injections the volunteers felt only localized pain; some reported drowsiness, increased thirst and polyurea. There was a slight, insignificant increase in body temperature and negligible decrease of blood pressure in some cases. In conclusion, it can be said that Ukrain is well tolerated in healthy volunteers in the doses of 5, 10, 20, and 50 mg/injection, even during prolonged (up to three years) administration. PMID- 1305043 TI - Clinical studies of Ukrain in terminal cancer patients (phase II). AB - Phase II of clinical studies was performed on 70 patients, ranging in age from 14 to 80 years, (27 male, 43 female) to determine the appropriate dose range for Ukrain and the clarification of dose/response relationships, in order to provide an optimal background for wider therapeutic trials. The following parameters were studied: physiological (pulse, blood pressure, temperature); biochemical, haematological and immunological. Electrolytes and trace elements were investigated, as well as neopterin, tumour markers, immune complexes, non specific blocking factors, development of tumours and metastases in quantitative respects (by X-ray, CT, scintigrams and US). The patients' general conditions were also assessed. Ukrain was given intramuscularly or intravenously every one, two, three, four or five days, or according to other schemata, in the dose range of 2.5, 5, 10, 15, 20 or 25 mg increasing (2.5 to 25 mg per injection), decreasing (25 to 2.5 mg per injection) and stable (5, 10, 15, 20 or 25 mg per injection). Duration of one course of therapy was between 10 days and 90 days. Intervals between courses ranged from 7 days to 3 months. In order to find dose/duration/interval/response-relationships, some cases were treated after chemoradiotherapy, some as adjuvant therapy to chemo-radiotherapy and alternatives such as iscador, and some as monotherapy. All patients were at terminal stages of their disease. PMID- 1305044 TI - Enhancement of macrophage tumouricidal activity by the alkaloid derivative Ukrain. In vitro and in vivo studies. AB - Ukrain is a semisynthetic drug with immunomodulatory properties, derived from Chelidonium majus L. alkaloids and thiophosphoric acid. The effect of this compound on the growth of Balb/c syngenic mammary adenocarcinoma was assessed. Intravenous, but not subcutaneous or intraperitoneal, administration of this drug was found to be effective in delaying tumour growth in an actual therapeutic protocol initiated five days after tumour implantation. No untoward side-effects were observed using these in vivo treatment modalities. The role of macrophages in the observed retardation of tumour development was investigated using peritoneal exudate macrophages (PEM) in cytotoxicity assays. In previous studies, the authors have found that PEM of mammary tumour bearing mice lose their capacity to kill a variety of tumour target cells including the in vitro cultured homologous tumour cells (DA-3). Pretreatment of PEM from normal mice with 2.5 microM Ukrain for 24 h followed by stimulation with either IFN-gamma or with LPS+IFN-gamma enhanced their cytotoxic activity. Treatment of PEM from tumour bearing mice with 2.5 microM Ukrain and LPS results in a reversal of their defective cytotoxic response against the DA-3 target cells. Furthermore, Ukrain alone, in the absence of a secondary signal, induced the activation of tumouricidal function of PEM from tumour bearing but not from normal mice. These data indicate that Ukrain's in vivo effects against the development of mammary tumours may be due, at least in part, to its ability to restore macrophage cytolytic function. PMID- 1305045 TI - Ukrain both as an anti cancer and immunoregulatory agent. AB - Thirty six stage III cancer patients were treated with Ukrain, a semisynthetic drug derived from Chelidonium majus L. alkaloids conjugated with thiophosphoric acid. The drug was injected intravenously every second day in a dose of 10 mg per injection. Each patient received 300 mg of the drug (30 injections). The cytostatic effect of Ukrain was monitored clinically and by ultrasonography (USG) and computer tomography (CT), as well as by determination of CEA and CA-125 in the sera of patients with rectal and ovarian cancers, respectively. The influence of Ukrain on immune parameters was evaluated by monoclonal antibodies (MAb) to CD2, CD4, CD8 and CD22. The influence of Ukrain on immune parameters in cancer patients was matched with its effect on these parameters in 20 healthy volunteer controls. The results obtained indicate that Ukrain, in a concentration not cytostatic in normal cells, is cytostatic for malignant ones, and may suppress the growth of cancer. The compound also has immunoregulatory properties, regulating the T lymphocyte subsets. PMID- 1305046 TI - Preliminary studies on the effect of Ukrain (Tris(2-([5bS-(5ba,6b,12ba)]- 5b,6,7,12b,13,14-hexahydro-13-methyl[1,3] benzodioxolo[5,6-v]-1-3- dioxolo[4,5 i]phenanthridinium-6-ol]-Ethaneaminyl)Phosphinesulfide.6HCl ) on the immunological response in patients with malignant tumours. AB - Preliminary clinical observations and studies on immunological response indicators were made in eight patients with malignant tumours, who had been administered parenteral injections of Ukrain. The results suggest that the preparation is a non-toxic immunostimulator inducing production of thymodependent T lymphocytes. The preparation improves general health of patients, has anti allergic action, and sedative and anti-inflammatory effects. It can inhibit growth of malignant tumours. PMID- 1305047 TI - Lymphocyte subsets in patients with lung cancer treated with thiophosphoric acid alkaloid derivatives from Chelidonium majus L. (Ukrain). AB - Lymphocyte subsets were evaluated in nine men (aged 42-68 years, mean 57 years) with histologically proven lung cancer, previously untreated. Lymphocyte subpopulations were quantified by immunofluorescence using monoclonal antibodies against total T-cells, T-helper and T-suppressor cells. In addition, the percentage of NK cells and the helper/suppressor (H/S) ratio were evaluated. The number of B-cells was determined by surface immunoglobulin immunofluorescence. Chelidonium majus L. (preparation Ukrain) was applied as an intravenous injection every three days. One course consisted of 10 applications of 10 mg each. All immunological tests were performed before and after drug administration. The treatment was generally well tolerated. The results showed an increase in the proportion of total T-cells, and a significant decrease in the percentage of T suppressor cells. The normalization of the H/S ratio was also noted. However, there were no signs of activation of NK, T-helper and B-cells. The restoration of cellular immunity was accompanied by an improvement in the clinical course of the disease. This effect was particularly pronounced in patients who responded to further chemotherapy. Objective tumour regression (CR+PR) was seen in 44.4% of treated patients. Four out of nine patients (44.4%) died of progressive disease during the course of this study. It is concluded that Ukrain can be immunologically effective in lung cancer patients and can improve human cellular response. PMID- 1305048 TI - The effects of thiophosphoric acid (Ukrain) on cervical cancer, stage IB bulky. AB - This study was carried out to determine the clinical and immune response of a stage IB voluminous uterine cervical cancer to thiophosphoric acid alkaloid derivatives from Chelidoniium majus L. (Ukrain). The drugs were administered 10 mg intramuscularly every other day, for up to 10 injections. The two largest diameters and tumour volumes were measured and laboratory and immunological tests were performed before and after Ukrain administration. The patients were then operated on with type III Piver's radical hysterectomy. Three out of nine eligible cases had partial responses while six cases remained stable. Decreased total B lymphocytes and suppressor T lymphocytes were observed as well as increased total numbers of T lymphocytes and helper T lymphocytes. There was no single case of clinical or haematological toxicity apart from mild nausea. Two patients were treated with adjuvant radiotherapy due to lymphatic involvement and all nine patients were still alive at least six months after follow-up. PMID- 1305049 TI - Chelidonium majus L. (Ukrain) in the treatment of cancer patients. AB - Ukrain, a semi-synthetic thiophosphoric acid compound of alkaloid chelidonine isolated from Chelidonium Majus L., Tris(2-([5bS-(5ba,6b,12ba)]-5b,6,7,12b,13,14- Hexahydro-13-methyl][1,3]-benzodioxolo[5,6-c]-1,3-dioxolo[4, 5- i]phenanthridinium-6-ol]-Ethaneaminyl) Phosphinesulfide 6HCl, causes a regression of tumours and metastases in many oncological patients. More than 400 documented patients with various carcinomas in different stages of development have been treated with Ukrain. The authors report on only three different cases treated with preparation Ukrain. Ukrain can be helpful in improving the general condition and prolonging life by reduction of the tumour progression and its immunomodulating effect on the organism. PMID- 1305050 TI - Effect of three months treatment with Ukrain on peripheral blood morphology in rodents. AB - Studies on Albino Swiss mice and Wistar rats have demonstrated that Ukrain administered intraperitoneally (i.p.) for three months produces the following effects in the haematologic parameters: increased leucocytes and decreased thrombocytes. The haemoglobin and erythrocyte levels, as well as haematocrit value, were unchanged. In the leucogram changes were observed; i.e., a fall in the number of neutrophil segments and an increase in the lymphocyte count. The erythrocyte indices, P.C.V., M.C.V., M.C.H. and M.C.H.C. were not changed by a period of three months i.p. Ukrain administration. The observed changes were more marked in female than in male animals and were greater in mice than in rats. PMID- 1305051 TI - Effect of single and three months treatment with Ukrain on aminotransferases (ALT and AST) and on the serum protein level in rodents. AB - The influence of Ukrain on the activity of aminotransferases (ALT and AST) and on the serum total protein content was estimated in mice and rats of both sexes receiving single or repeated doses of the drug. It was found that one hour after intraperitoneal (i.p.) administration of Ukrain no characteristic changes were recorded in the activity of the investigated enzymes, or in the serum protein content of animals of either sex. Similar effects were observed after three months treatment with Ukrain in rats of either sex. Only in mice receiving Ukrain for three months was a rise in ALT and AST activity found. No particular changes were observed in the total serum protein level, except for a small decreases in the sera of male mice. PMID- 1305052 TI - Effect of single and prolonged administration of Ukrain on prolactin concentration in rats. AB - The effect of single and prolonged administration of Ukrain on the serum prolactin concentrations in rats of both sexes was investigated. One hour after intraperitoneal (i.p.) administration of Ukrain in rats, in doses of 7, 14 and 28 mg/kg, the drug did not affect their serum prolactin concentration. Only in a dose of 28 mg/kg did this drug decrease serum prolactin in a group of female rats. Repeated i.p. treatment (once daily for three months) with 7, 14 and 28 mg/kg of Ukrain significantly increased the serum prolactin concentration in rats of both sexes. The most marked effect was observed in the group of female rats. PMID- 1305053 TI - Interaction between Ukrain and aminophenazone in analgesic tests in rodents. AB - The effect of Ukrain on the analgesic activity of aminophenazone was studied in mice and rats. Antinociceptive action induced by aminophenazone in doses of 50 or 100 mg/kg intraperitoneally (i.p.) was determined by using the writhing syndrome, hot-plate tests and tail-flick latency. The action of aminophenazone was significantly enhanced by Ukrain in the writhing syndrome test and in the tail flick test. Antinociceptive action of aminophenazone was decreased by Ukrain in the hot-plate test in mice. These results suggest that Ukrain, given simultaneously with aminophenazone, changes susceptibility of animals to nociceptive reaction in the tests performed. PMID- 1305054 TI - The role of microorganisms in endodontic disease. PMID- 1305055 TI - Proteinaceous constituents of human saliva. PMID- 1305057 TI - Test your diagnostic skills. Oral squamous cell carcinoma. PMID- 1305056 TI - Osteochondroma of the mandibular condyle: case report. PMID- 1305058 TI - Diseases of the temporomandibular joint: surgical management. PMID- 1305060 TI - The influence of exogenous oxytoxin on labelling of secretory epithelium of mouse mammary gland by [3H]leucine, evidenced by autoradiography. AB - It has been suggested that oxytocin, besides its milk-ejecting activity, is also involved in the hormonal regulation of the mammary gland secretory cells. The available data, however, are conflicting. In this study two independent experiments, separated by a certain time interval show that oxytocin intravenously administered to mice at days 10-14 of lactation diminished the incorporation of [3H]leucine into the mammary gland tissue by 32 and 53 per cent, respectively. The neurohormone was co-injected with the tracer amino acid. The radioactivity taken up by the secretory cells was estimated by light microscopic autoradiography. The autoradiograms were evaluated by visual silver grain counting. Tissue radioactivity was measured by liquid scintillation counting. A milk stasis in the mammary gland induced by depriving the mice of suckling two hours before tracer injection had no influence on the secretory activity of the glandular cells. It is assumed that oxytocin has a direct effect on the milk producing cells, and that the reduction in measurable radioactivity caused by the neurohormone may be due to an accelerated intracellular passage of labelled milk proteins. PMID- 1305061 TI - Serum levels of steroid hormones in men with varicocele and oligospermia as compared to normozoospermic men. AB - In order to assess the contribution of individual steroidogenic organs to over all steroid biosynthesis, the basal plasma levels of six hormonal steroids, reflecting the function of gonads and adrenals, as well as both gonadotropins and prolactin, have been determined in 63 oligo- and/or asthenozoospermic men with palpable varicocele, confirmed in each case by sonography. The values obtained were compared with the results of a group of age-matched normospermic men without endocrine disorders. Insignificantly lower levels of testosterone accompanied by significantly lower levels of dihydrotestosterone, slightly decreased LH but increased FSH undistinguishable concentrations of cortisol in patients with varicocele were in agreement with previous findings. Higher levels of an exclusively adrenal androgen 11 beta-hydroxyandrostenedione in men with varicocele indicate increased activity of the adrenal cortex. Significantly higher basal levels of 17 alpha-hydroxyprogesterone in the patient group (p < 0.001), so far not unequivocally proved, evidence for suggested decreased enzyme activity of C17-20 lyase in the testis in at least some of men with varicocele. PMID- 1305059 TI - Ultrastructural-morphometric effects of radiotherapy on pituitary adenomas in acromegaly. AB - Within a series of 22 irradiated GH-producing adenomas we studied by light microscopical and morphometrical means the grading of nuclear pleomorphism, the proportion of densely granulated cells, the number of mitoses, multinuclear cells, necrotic or necrobiotic cells, and the degree of fibrosis in comparison to non-irradiated tumours. By electronmicroscopical morphometry we investigated the changes in area, circumference, area percentage, and number of intracellular structures. The rate of necrobiotic cells and the grade of nuclear pleomorphism were significantly higher in the irradiated tumours. The fibrotic areas were larger. No differences were observed in the degree of granulation and the rate of multinuclear cells. Mitoses were found in only one tumour. Within the group of the well-differentiated adenomas the areas and circumferences of the nuclei, nucleoli, mitochondria, immature secretory granules, and secretory granules increased significantly. The area percentages of the nuclei, mitochondria, immature secretory granules, and secretory granules increased as well. The mitochondria, Golgi-fields, and the rough endoplasmatic reticulum decreased in number. The undifferentiated adenomas changed almost in the same significant way. To us most of these changes are a sign of irradiation damage. The enlargement of intracellular structures could be a sign of an increased rate of secretory activity. PMID- 1305062 TI - Glycoregulation is not altered by short-term administration of diltiazem in nondiabetic humans. AB - In this study changes in glucose assimilation during an intravenous glucose tolerance test (IVGTT) was investigated in 12 clinically healthy normotensive women with a body mass index (BMI) of 25 kg/m2 (range 22-31). This was assessed by coefficient Kg, the level of glycosylated proteins and insulin, C-peptide and contraregulating hormone secretion after seven days of oral administration of diltiazem, a calcium current blocker (180 mg per day). In spite of the fact that diltiazem protracted electrocardiographic QT interval from 0.16 +/- 0.008 to 0.18 +/- 0.009 s. (p < 0.01), QaT from 0.29 +/- 0.007 to 0.31 +/- 0.008 s. (p < 0.05), QeT from 0.35 +/- 0.009 to 0.37 +/- 0.009 s. (p < 0.01), it did not affect Kg in any significant way, nor did it affect the glycosylated protein levels, insulin and C-peptide secretion, nor the secretion of adrenaline, noradrenaline, dopamine, cortisol and growth hormone. Thus although diltiazem is a highly effective drug as far as the cardiovascular system is concerned, short-term administration of therapeutic doses of 180 mg/day is not associated with glycoregulatory risks. PMID- 1305063 TI - Altered terminal glycosylation of thyroglobulin in papillary thyroid carcinoma. AB - Samples of thyroglobulin (Tg) were isolated from specimens of differentiated thyroid carcinoma of the papillary type and from normal adjacent glandular tissue, and the content of sialic acid was estimated. Also the in vitro incorporation of 14C-sialic acid, in the form of both CMP (cytidine 5' monophospho-)--activated and non-activated N-acetyl-neuraminic acid, into Tg of malignant and morphologically normal thyroid. The sialic acid content of Tg preparations from papillary thyroid carcinomas varied considerably (0.27-0.92 mg/100 mg Tg). In six cancerous Tg samples the content of sialic acid was markedly lower than that in Tg from the corresponding apparently normal thyroid tissue (0.71:1.11 mg per 100 mg Tg). In addition, in comparison with the control, the incorporation of non-activated 14C-sialic acid into Tg of malignant thyroid tissue was considerably lower (-41%). However, the incorporation of CMP-activated 14C-sialic acid into cancerous Tg was greater than into Tg of morphologically unchanged tissue of the same gland (+29%). The reduced content and incorporation rate of sialic acid into Tg of differentiated thyroid carcinoma is probably the consequence of disturbances in terminal glycosylation of the Tg molecule in malignantly transformed thyroid tissue. The enhanced incorporation of CMP-sialic acid into cancerous Tg suggests that Tg sialylation in carcinoma is probably altered in the sialic acid activation phase. PMID- 1305064 TI - The influence of testosterone substitution on bone mineral density in patients with Klinefelter's syndrome. AB - The aim of this study was to clarify the extent of bone mineral deficiency in patients with Klinefelter's syndrome on the premise that testosterone substitution could prevent this deficiency. Bone mineral density was measured by single-photon absorptiometry in 42 patients with Klinefelter's syndrome, (21 patients without therapy, 10 with testosterone substitution before the age of 20 and 11 patients with testosterone substitution beginning after the age of 20). We found significantly lower bone mineral density in patients without therapy and in patients when the therapy began later compared to normal individuals. Patients with early therapy showed a high proportion of normal values of bone mineral density. We found a positive correlation between bone mineral density and plasma testosterone and a negative correlation between plasma testosterone and age for patients without therapy. These findings suggest that low testosterone levels before or during puberty cause inadequate bone development and low bone mineral density in Klinefelter's syndrome. Only early testosterone substitution may prevent bone mineral deficiency. Later substitution no longer affects bone mineral density. PMID- 1305065 TI - Further findings on the inhibitory effect of estradiol benzoate on the circulation and on 45Ca and 3H-proline incorporation in rat bones. AB - Various aspects of the effect of estradiol benzoate (EB, Agofollin Depot, Czechoslovakia, usually in a s.c. dose of 5 mg/kg body weight once a week), on the local circulation (the uptake of 85Sr-microspheres), the incorporation of 45Ca and 3H-proline, bone density and ash weight related to bone volume were studied in six experiments in the tibia and distal femur of 224 rats. 1. The dose response. In rats treated four weeks with doses of 0.5, 1.0, 1.5 and 2.0 mg EB per rat once a week, a significant correlation with the uptake of 85Sr microspheres (r = -0.56), the blood flow (r = -0.56), the incorporations of 45Ca (r = -0.89) and 3H-proline (r = -0.35) and body weight (r = -0.71) was demonstrated. 2. The time course of changes after 1, 2, 4 and 8 weeks administration of EB. Circulatory values were not significantly lowered until after four weeks, 45Ca incorporation and body weight were significantly lower after only one week and 3H-proline incorporation did not fall until after eight weeks. The course of the uptake of 85Sr-microspheres and the incorporation of 45Ca were very similar. 3. Comparison of males and females. EB reduced circulatory values and 45Ca and 3H-proline incorporation and increased bone density and bone ash weight in both males and females. Conclusions. The decrease in the local bone blood flow after EB showed a significant dose-effect correlation; the decrease in circulatory values, on using the given administration method, is significant after four weeks. The inhibitory effect of EB on the bone blood flow is not sex-specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305066 TI - Critical care hypercalcemia--a hyperparathyroid state. AB - Hypocalcemia is a well known finding in critically ill patients. Subsequent occurrence of mild hypercalcemia has also been reported. In order to investigate the incidence and nature of critical care hypercalcemia serum calcium was measured in 83 critically ill ICU patients (TISS score > or = 40) and related to the occurrence of acute renal failure (ARF) and severity of illness, evaluated by the APACHE-II and the multiple organ failure scoring systems. Thirty-two percent of the patients developed hypercalcemia (serum calcium > or = 2.60 mmol/l) during their ICU stay. These hypercalcemic episodes (mean maximal value 2.71 +/- 0.12 mmol/l) were more common and occurred earlier in patients with co-existing ARF. However, multiple regression analysis showed the number of failing organ systems in the first days to be the best predictors for later occurrence of hypercalcemia (p < 0.0001). When serum parathyroid hormone (PTH) was measured in 6 of the patients without ARF during their hypercalcemic episodes, PTH was not suppressed but slightly elevated, to a similar extent as in patients with mild primary hyperparathyroidism. In conclusion, a high incidence of hypercalcemia was found in critically ill ICU patients. The hypercalcemia was mild and was more frequently found in patients with co-existing renal failure. The most powerful predictor to later occurrence of hypercalcemia was however the severity of the illness in itself. The raised levels of PTH found during the hypercalcemic episodes suggest ICU hypercalcemia to be caused by parathyroid overactivity. PMID- 1305067 TI - Thyrotropin-releasing hormone (TRH) and vasopressin and oxytocin release: in vitro as well as in vivo studies. AB - Rats euhydrated and dehydrated for two or four days were given intracerebroventricularly (i.c.v.) thyrotropin-releasing hormone (TRH) in a daily dose of 200 ng dissolved in 10 microliters of 0.9% sodium chloride.) A single dose of TRH administered to euhydrated animals was followed by a significant increase of the vasopressin content in the neurohypophysis and hypothalamus as well as of the hypothalamic oxytocin content. On the contrary, a single dose of TRH decreased the oxytocin content in the neurohypophysis. Under conditions of dehydration TRH distinctly restrained the decrease of vasopressin and oxytocin in the hypothalamus. In animals dehydrated for two or four days the decrease of oxytocin in the neurohypophysis, brought about by stimulation of osmoreceptors, was distinctly more marked under treatment with TRH. On the contrary, the depletion of neurohypophysial vasopressin was significantly less apparent under such conditions. 28 nmol/L TRH markedly increased vasopressin release but inhibited that of oxytocin from the neurointermediate lobes incubated in vitro both under basal conditions as well as during stimulation with excess (56 mmol) potassium. PMID- 1305068 TI - Postoperative hyperglycaemia--are the patients diabetic? AB - The aim of this study was to investigate the occurrence and causes of postoperative hyperglycaemia. Blood sugar was measured after operation in 262 patients who had undergone minor emergency operations, when the patients were receiving 5% glucose infusion at the rate of 170 ml/h. In 32 patients (12%) blood glucose was over 8.0 mmol/l. Serum insulin concentration in these patients was significantly higher than in reference patients, who had blood glucose below 5.5 mmol/l. The number of insulin receptors in red cells and the affinity of insulin to receptors were similar in both groups. Serum cortisol was higher, but free fatty acid concentration lower, in the hyperglycaemic group than in the reference group. The tests done postoperatively were repeated two weeks later without surgical stress. The values recorded, indicating the patients' normal metabolism, did not differ between the two groups, except that serum cortisol was somewhat higher in the reference patients. The oral glucose tolerance test was normal in all patients except one. The results suggest that patients prone to postoperative hyperglycaemia are not diabetic, but that their production of glucose is increased during surgical stress. PMID- 1305069 TI - The effect of azathioprine, cyclosporine A and insulin on the in vitro lymphocyte mediated cytotoxicity in type I diabetic patients. AB - Previously both specific and nonspecific immune reactions have been reported in patients with type I diabetes mellitus. In this study the effect of various immunosuppressive drugs and insulin was studied on in vitro lymphocyte-mediated cytotoxicity in 20 type I diabetic patients. Twenty sex- and age-matched healthy subjects served as controls. Human pancreas-extract (300 micrograms/ml protein) coated, 51-Chromium labeled chicken erythrocytes were used as target cells and separated T-lymphocytes as effector cells with and without azathioprine 50 micrograms/50 microliters (Wellcome), Cyclosporine A 5 ng/50 microliters (Sandoz) and MC Actrapid insulin 0.1 IU/50 microliters (Novo). The degree of cytotoxicity was expressed with cytotoxic capacity: the number of maximal killed target cells. Simultaneously islet cell antibodies (ICA) in sera and the number of activated T lymphocytes were assessed. Significant lymphocyte-mediated cytotoxicity was observed in the majority of type I diabetic patients (18/20), while no cytotoxicity was found in the control cases. The cytotoxicity decreased in all 16 patients using azathioprine or insulin, independently of ICA and HLA-DR positivity. The number of killed target cells was lowered considerably by Cyclosporine A in all 18 patients having cytotoxicity against pancreas-extract. Our observations reveal that Cyclosporine A proved to be the most effective immunosuppressive agent in vitro. It decreases not only the leucocyte migration inhibition as previously observed, but also the lymphocyte-mediated cytotoxicity, which represents the late stage of cellular immune reactions against pancreatic tissue. PMID- 1305070 TI - Adrenergic mechanism in hyperketonemia in thyrotoxic and starved rats. AB - To evaluate the possible role of the adrenergic mechanism in hyperketonemia in hyperthyroidism and starvation, the plasma concentrations of FFA, acetoacetate (AcAc), and beta-hydroxybutyrate (BOHB) were measured in thyrotoxic and starved rats for 96 hours. Thyrotoxemia was induced in rats by a daily subcutaneous thyroxine (100 micrograms/kg/day) injection carried out for 7 days. Some of the thyrotoxic and starved rats were administered subcutaneous phentolamine (2 mg/kg, twice daily) or propranolol (0.1 mg/kg, twice daily). Plasma levels of FFA, AcAc, and BOHB were significantly increased in thyrotoxic and starved rats compared with the control rats. Phentolamine and propranolol administration did not alter plasma levels of FFA, AcAc, and BOHB in thyrotoxic rats. In starved rats, propranolol did not alter plasma levels of FFA, AcAc, and BOHB, however, phentolamine did increase plasma levels of FFA, AcAc, and BOHB. These results indicate that the adrenergic mechanism may not contribute to the hyperketonemia in thyrotoxic rats, but may have a slight inhibitory effect on ketogenesis in starvation probably due to alpha-antilipolytic action. PMID- 1305072 TI - [Physiologic bases of the method to increase nonspecific resistance of the organism by adaptation to intermittent normobaric hypoxia]. AB - Impulse biorhythm of cyclic pO2 change in the uterus tissues and intrauterine fetus of rats, guinea pigs and dogs is regarded as evolution-fixed, physiological mechanism aimed at increasing nonspecific resistance of the fetus. Modeling of this mechanism by adaptation to intermittent normobaric hypoxia under impulse conditions permits more significantly increasing nonspecific resistance of the organism than application of hypoxic effect under constant conditions. PMID- 1305071 TI - The role of limbic-hypothalamic systems in metabolic responses of phenylalanine to repeated cold exposures in rabbits. AB - In this study we examine the effects of lesions to limbic or hypothalamic structures on the metabolic responses of phenylalanine in liver slices prepared from rabbits exposed to cold stress (-20 degrees C) for 12 hours at a fixed time once a day. The results were as follows: 1. The 1st cold exposure (cold exposure on the 1st day) had marked and various effects on phenylalanine metabolism, and the metabolic responses of phenylalanine to cold exposure gradually decreased and then completely disappeared with repetitions of exposure in intact rabbits. 2. The metabolic patterns and responses of phenylalanine to the 1st cold exposure were altered by lesioning the periventricular arcuate nucleus (ARC), ventromedial hypothalamus (VMH), stria terminalis (ST) or dorsal fornix (FX). 3. The complete abolishment of the metabolic responses to cold exposure by its repetition was observed in rabbits with lesions in the ARC or VMH as well. 4. In contrast, metabolic responses of phenylalanine to cold exposure in rabbits with lesions in the ST or FX remained even after six exposures. These results suggest that the ARC, VMH, amygdala (AMYG)-ST system and dorsal hippocampus (HPC)-FX system played a role in the metabolic regulation of phenylalanine and in the metabolic responses of phenylalanine to the 1st cold exposure and that the AMYG-ST and HPC FX systems, but not the ARC or VMH, participated in the process of the metabolic adaptation of phenylalanine to cold exposure. PMID- 1305073 TI - [Effect of inhalation therapy on the dynamics of electroencephalographic and rheoencephalographic indices in patients with vasomotor dystonia and with pathology of respiratory organs]. AB - Dynamics of electro- and rheoencephalographic (EEG and REG) indices in patients with some forms of cephalgia (vegetovascular dystonia--VVD) as well as with chronic nonspecific pulmonary diseases has been studied under the effect of artificial mountain climate therapy conducted using a special chamber "Orotron" created by a collective of researchers from Academy of Sciences of Ukraine. The results of EEG and REG analysis reflect a general tendency to improvement of the bioelectrical brain activity and cerebral hemodynamics. PMID- 1305074 TI - [Pathophysiologic mechanisms of cardiorespiratory system dysfunction in high school children with chronic obstructive pulmonary diseases]. AB - The basic indices of the cardiorespiratory system function, gas exchange, regional pulmonary functions have been studied. It is stated that a group of children with a higher level of oxygen consumption (hyperergic type) as against a control group is characterized by disorder in permeability of terminal branches of a bronchial tree, by the development of acute obstructive emphysema, increase in alveolar ventilation with relative decrease in minute blood volume, arterial hypoxemia with possible emergence of tissue hypoxia. A decrease in permeability of large bronchi were observed in a group of children with a low level of oxygen consumption (hypoergic type). Due to this decrease the hypoventilation zones appeared. It caused the development of arterial hypoxemia, but a risk of the tissue hypoxia emergence was insignificant. PMID- 1305075 TI - [Artificial mountain climate in therapy and rehabilitation of patients with chronic nonspecific pulmonary diseases]. AB - Therapeutic efficiency of artificial Alpine climate was studied in a group of 318 patients with chronic nonspecific pulmonary diseases (CNDP). The Alpine climate was modelled on device "Orotron". The base, progradient and prolonged regimes of therapy by artificial Alpine climate (orhotherapy) were used in work. It is shown that application of optimal conditions of orhotherapy promotes normalization of the external respiration function in patients with CNPD due to a decrease in expression of broncho-obstructive and bronchitic syndromes and in nonuniformity of regional ventilation of lungs. Therapy by artificial Alpine climate is recommended to be used in wide clinical practice for treatment and rehabilitation of patients with CNDP. PMID- 1305076 TI - [Physiological premises and mechanisms of normalizing effect of normobaric hypoxia and inhalation therapy]. AB - Pathogenetic and physiological aspects of hypoxia problems have been considered. An opinion is stated that normalizing effect of intermittent normobaric hypoxia (INH) with short-term respiration of gaseous mixture containing at least 10% of oxygen in nitrogen is based on biorhythm inherent in all the living organisms with replacement of the high functional activity periods by the periods of rest and restoration with temporary physiological hypoxia as their typical companion. It is shown that for numerous diseases the course of INH or sessions of staying in the chamber of artificial mountain climate normalize the state of central nervous system, blood circulation, respiration, hemopoiesis and immunological reactivity, activate natural protective mechanisms and increase functional reserves of the organism. Allowing for anthropogenic pollution of the environment and its consequences for the health, it is advisable to widely adopt hypoxytherapy and orrhotherapy. PMID- 1305077 TI - [The use of hypoxic stimulation in chronic and relapsing bronchitis in young children ]. AB - 214 children of different age with various forms of bronchitis were subject to immunological and biochemical examination. Against a background of hypoxic state of patients the values of quantitative indices of cellular immunity (E-RFC, blast transformation reaction with phytohemagglutination) were revealed to decrease and dysimmunoglobulinemia-to form. It is shown that in the period of exacerbation of clinical symptoms of bronchitis the concentration of malonic dialdehyde and resistance of erythrocyte membranes to peroxide hemolysis significantly increase. Analysis of peroxidation level against a background of improvement of clinical indices after the performed treatment indicates that there is no tendency to normalization of metabolic disorders. The above results show that it is necessary to carry out normobaric hypoxic stimulation aimed at treating and preventing bronchitis in children of early age. PMID- 1305078 TI - [Effects of hypoxic stimulation in experimental animals and in children with bronchial asthma]. AB - Inhalations using hypoxic mixture of 12-15% O2 were tested in 40 rats (daily for 20 min. during 1-4 months) and in 200 children with light and mid-serious forms of bronchial asthma (for 5-10 min. 2-4 times with 5 min. break, course-10 days). Stimulation effect in animals was observed for 1-2 months and then depression came. The immunological and allergological indices were observed to distinctly improve, whereas the indices of the pulmonary function remained practically unchanged. The clinical indices in most patients improved and the similarity of this method and effects of other nonmedicamental methods was noted. PMID- 1305079 TI - [Results of utilization of intermittent normobaric hypoxia in patients with bronchial asthma and chronic obstructive bronchitis]. AB - The results of intermittent normobaric hypoxytherapy in 42 patients with bronchial asthma (BA) and 14 patients with chronic obstructive bronchitis (COB) are analyzed. The positive effect is obtained in 76% of patients with BA and 92.8% of patients with COB. In the group of patients with BA the best effect was achieved for atopic form of BA--in 90% of patients, the effect was less pronounced for infection-allergic form--in 73.9% and for mixed form of BA--in 66.7%. In the process of treatment the attacks of asphyxia disappeared or became more occasional in 60.7% of patients; in 32.1% the attacks were more easily arrested or stopped independently; 33.8% of patients decreased doses of constantly taken drugs; in 33% cough ceased or decreased, sputum became to expectorate better; in 41% of patients dyspnea disappeared and considerably decreased. Improvement of the state in 54% of patients was retained for one year and more, in 29%--for 6 months, in 16.6%--for 3-4 months. The course of treatment consisted of 20-25 sessions. The patients breathed in hypoxic gas mixture containing 10% of oxygen (HGM-10) under intermittent conditions alternating with respiration of free air. PMID- 1305080 TI - [Hyperventilation syndrome and reflexologic methods of its correction]. AB - Acupuncture has been studied for possibility to be used for correction of hyperventilation disorders. Diagnostics of hyperventilation syndrome (HVS) was carried out on the basis of data of clinical, laboratory and functional methods. Acupuncture was carried out using the first (strong) variant of classical inhibitive procedure of acupuncture. It was shown that reflex therapy decreased electroencephalographic characters of dysrhythmia and exaltation and paroxysmal activity as well as inter-hemisphere asymmetry in patients with HVS. Parallel with a decrease in the degree of negative subjective sensations, minute respiratory volume, non-informity of regional ventilation were observed to decrease and partial oxygen pressure in alveolar air--to increase. The positive results of reflex therapy of HVS indicate that it is possible to correct hyperventilation disorders using no pharmacotherapy. PMID- 1305081 TI - [Effect of inhalation of surface-active substances on the surfactant system of the lung]. AB - Surface activity, biochemical composition and morphology of the rat lungs were studied in norm, under effect of acute hypoxia and after infusion of obsidan (1 mg/100g). The data permit suggesting that under the influence of obsidan and hypoxia a stability index of surfactants and quantity of phospholipids decreased, while the quantity of lysophosphatidylcholine and lysophosphatidylethanolamine increased. Morphology studies show that after hypoxia and obsidan infusion oedema and cell destruction developed in the lung. The inhalation of exogenous surfactant increased stability index and quantity of phospholipids, decreased the quantity of lysophospholipids but did not eliminate morphological disorders in the lung induced by hypoxia and obsidan infusion. PMID- 1305082 TI - [Effect of intermittent normobaric hypoxia on dynamics of disease state in patients with hypertension]. AB - Curative effect of intermittent normobaric hypoxia created when breathing in gaseous hypoxic mixture containing 10% of oxygen and 90% of nitrogen has been examined in 41 patients with hypertonic disease. Adaptation to hypoxia has been studied for its effect on the central hemodynamics psychoemotional state and kinetics of oxygen supply of the skin. The pronounced positive effect of treatment was achieved in 70.7% of patients, the arterial pressure decreasing at the expense of different mechanisms depending on the type of blood circulation. Besides, a decrease in the emotional tension of patients and normalization of oxygen consumption and transport were observed. PMID- 1305083 TI - [Effect of intermittent normobaric hypoxic activity on the development of acute radiation disease]. AB - The experiments on 260 male mice of colony SHK, 352 mongrel rats and 20 Wistar rats were carried out to study the ability of using the normobaric hypoxic stimulation method for acute radiation sickness. Hypoxic stimulation using gas mixture with 10% of oxygen and 90% of nitrogen was conducted for two weeks after irradiation for 30 min. every day. It is shown that under influence of ionizing radiation (7 and 5.5 Gy) the postradiation hypoxic action increased the 30-day survival rate of mice, reduced disturbances of the qualitative composition of leukocytes in peripheric blood, promoted more rapid restoration of thromboelastography indices and caused no reliable changes in the postradial content of albumin and creatinine in blood. PMID- 1305084 TI - [Manifestation of oxygen effect during normobaric hypoxic hypoxia in the intrauterine and postnatal developmental periods]. AB - The experiments on rats have shown that hypoxic gas mixture containing 10% of oxygen and 90% of nitrogen (HGM-10) under normobaric conditions exerts a highly reliable radioprotective effect on progeny when 11-day pregnant animals are exposed to total irradiation (60Co, 20 Gy). As distinct from the known radioprotector, mexamine, (5-methoxytryptamine), HGM-10 has a pronounced radioprotective effect during the first days (1-5) after birth. Radioresistance of new-born rats correlates with the level of pO2 in the tissues which progressively decreases with respiration of HGM-10 and remains unchanged after mexamine (10 mg/kg) introduction. PMID- 1305085 TI - [Use of respiratory mixture containing 8.0-8.5% of oxygen in hypoxic radiotherapy of cervical neoplasms]. AB - Combined radiotherapy of patients with cervical carcinoma of stages IIb and IIIb was conducted. Hypoxia (8.0-8.5% of O2 in the respiratory mixture) was used in microfractionated (2 Gy) irradiation of metastatic spreading zones. When irradiating under conditions of hypoxia, the number of fractions was brought up to 28 as compared to 20 in control. Despite a 40%-increase of the dose, seriousness of radiation reactions and remote injuries remained at the same level. It is found that patients endure well the respiratory mixture for 6 min. necessary for irradiation. PMID- 1305086 TI - [Radioprotective action of gas hypoxia (8%) in local irradiation of the kidneys]. AB - The radioprotective action of hypoxia in local irradiation of kidneys was studied. The experiments were carried out on hybrid mice (CBA x C57Bl) exposed to local X-ray irradiation through a lead diaphragm matched to the kidneys. In the experimental group the animals breathed in gaseous mixture with 8% of oxygen prior to and during irradiation. 20-36 weeks after irradiation the functions of glomerular and juxtaglomerular systems, as well as mass of native and dried kidneys were studied in the animals. It is shown that hypoxia efficiently protects kidneys against irradiation and permits increasing the supplied dose of radiation at least by 25%. High-efficient protection is retained when passing from single to fractionated irradiation. PMID- 1305087 TI - [Morphofunctional characteristics of murine kidneys in single and fractionated irradiation in air and hypoxia (8% of O2)]. AB - The protective effect of hypoxic gas mixture containing 8% of oxygen (HGM-8) has been studied in long terms after local single and fractional X-ray irradiation of the kidney in mice. Some criteria of injury shown that hypoxia protects the kidneys against irradiation, changes in irradiation dose constituting 1.25-1.33. When passing from single irradiation to five-fold daily one, the protective effect of hypoxia does not fall significantly. PMID- 1305088 TI - [State of the free-radical oxidation system in normobaric hypoxia]. AB - The experiments on the rats have revealed that 7-hour action of 10% hypoxic gas mixture (HGM-10) exerts no effect on the parameters of Fe(2+)-induced chemiluminescence and rate of accumulation of TBA-active products in the heart, liver, kidney, brain tissues and blood plasma. Two-week adaptation to intermittent effect of HGM-10 causes some activation of free-radical oxidation recorded in blood plasma and the more pronounced increase in power of the endogenic antioxidant system. It is assumed that the revealed changes in the state of the homeostatic system of free-radical oxidation and antiradical protection of the organism are of importance in the mechanism of the known preventive and curative action of intermittent normobaric hypoxia. PMID- 1305089 TI - [Effect of ceruloplasmin on the oxygen tension in muscular tissue of experimental animals]. AB - The polarographic method using platinum electrode has been applied to study the effect of ceruloplasmin (CP) on the oxygen tension (pO2), oxygen saturation rate and rate of oxygen utilization in the muscular tissue of high-leukemic AKR mice, C57BL/6 mice with transplanted Lewis lung carcinoma (3LL) and rats after gamma irradiation in a dose of 7 Gr. It has been shown that CP in AKR mice improves oxygen saturation of the muscular tissue. This effect is also evident in the case of the marked pO2 decrease in the muscle and its oxygen saturation rate (animals with Lewis lung carcinoma and after gamma-irradiation). PMID- 1305090 TI - [Some mechanisms of antihypoxic action of taurine]. AB - It is shown that preliminary taurine treatment prevents the disturbances of energy metabolism in the brain, heart and liver tissues of Wistar rats with acute hypoxic hypoxia. Administration of taurine restored to normal the parameters of adenine pool: the concentration of ATP increased within the cytoplasm, while that of ADP and AMP diminished; mitochondrial respiration proceeded more rapidly; the concentrations of pyruvate and malate decreased; isocitrate dehydrogenase activity, P/O and NAD/NADH ratios increased. Taurine treatment resulted in a decreased level of lipid peroxides in the rat tissues with hypoxia. The role of intracellular calcium content and biomembranes structure changes as the mechanisms of taurine action on energy metabolism and lipid peroxidation is discussed. PMID- 1305091 TI - [Antihypoxic effect of glucosamine in acute hypoxic states in mice]. AB - The preventive glucosamine injection causes an increase in the survival of mice with acute hypobaric hypoxia. The injection of glucosamine, combined with sodium hydroxybutyrate greatly increased their antihypoxic activities. PMID- 1305092 TI - [Membrane technology as a basis for creation of treatment-and-prophylactic equipment for inhalation therapy and normobaric hypoxia]. AB - The principles of membrane technology of gas distribution have been considered, that has a wider adoption in different branches of economy and in medicine. One of the promising trends of membrane technology employment is production of respiratory gas mixtures for hypoxytherapy, non-medicamental method to increase the human organism resistance to numerous pathogenetic environmental factors. Gas distributors and devices with different surface mass exchange and wide range of operating stress using hollow selectively permeable fibers of poly-4 methylpentene-1 are designed and produced under conditions of scientific productions. The technology of hollow fibers formation has been tried out on production spinning machinery of enterprises of chemical fibers in Ukraine. Design of gas distributors permits supplying them as a part of different devices of normobaric hypoxia from individual ones to devices of joint use allowing for customer's demands. PMID- 1305093 TI - [Effect of intermittent normobaric hypoxia on gastric and duodenal mucosa in man]. AB - Clinical and laboratory examinations of 11 patients with peptic ulcer have shown that combined treatment using sessions of intermittent normobaric hypoxytherapy (10% of oxygen in 90% of nitrogen, length of respiration is 7 min., respiration of free air 3 min., such 6 cycles for 1 hour) promotes healing of ulcers, decreases dyspepsic and astheno-neurotic symptoms of disease. The method can be recommended for treating the patients with peptic ulcer and for preventing seasonal acute attacks in patients with relapses of this disease. PMID- 1305094 TI - [Effect of hypoxic hypoxia on immune reactivity and some factors of nonspecific resistance of humans and animal organisms]. AB - Evidences available in home and foreign literature concerning the effect of normobaric hypoxia, adaptation to mountain climate conditions and trainings in barochamber on cellular and humoral indices of immunity have been critically considered. The data on the influence of permanent residence under mountain conditions on the level of sickness rate of population, bioenergy indices, and activity of the opiate brain system have been studied as well. The analyzed data indicate that it is expedient to use normobaric hypoxia for effects on the state of immunic organism system. PMID- 1305095 TI - Infection control is a practice-builder. PMID- 1305097 TI - Esthetic controls for anterior restorations. PMID- 1305096 TI - Gain acceptance with high-tech. PMID- 1305098 TI - Tooth preparation for ceramometal and ceramic restorations: anterior teeth. PMID- 1305099 TI - Multidisciplinary approach to a complex situation. PMID- 1305100 TI - Routine restorative procedures that yield predictive results. PMID- 1305101 TI - Who should place amalgam restorations? PMID- 1305102 TI - Staff survey shows higher pay for hygienists. PMID- 1305103 TI - Scheduling for the productive practice. PMID- 1305104 TI - Contract staffing or co-employment? PMID- 1305106 TI - What message are you sending? PMID- 1305105 TI - An 1870s building is renovated for dentistry. PMID- 1305107 TI - New technologies enhance clinical photography. PMID- 1305108 TI - Guard against seller's remorse. PMID- 1305109 TI - Estate-planning preserves practice value. PMID- 1305110 TI - The last life insurance article you'll ever have to read. PMID- 1305111 TI - [Endoscopic sclerotherapy of esophageal varices in pediatric patients]. AB - Endoscopic sclerotherapy was performed for esophageal variceal sclerosis in 7 children, aged 18 months to 11 years. Five of them had cavernomatous portal degeneration and the other two hepatic cirrhosis. The technique used was intra- and perivariceal with ethanolamine oleate in order to get the decrease or disappearance of the variceal veins. Two of the patients showed retrosternal pain and fever after the sclerosis procedure. This preliminary report shows that endoscopic sclerosis of esophageal varices is a good procedure to control acute bleeding and to prevent its onset in children. PMID- 1305112 TI - [Role of flexible sigmoidoscopy in the early detection of colorectal tumors]. AB - In a large endoscopic population screening study for colo-rectal polyps and cancer among 2,080 average-risk asymptomatic or with minor GI symptoms, adults of both sex, average age 56.2, were submitted to flexible sigmoidoscopy 60 cm as part of a preventive medical checkup. Procedure was very effective: 349 polyps were detected in 276 patients, with a total polyp incidence of 13.3%. In 174, more than 60% of such cases, endoscopic polypectomy was performed: 118 were tubular benign adenomas, 57 hyperplastic, 7 mixed types adenomas, 3 carcinomas in situ Dukes A, 2 villous adenomas one of them malignant, one leiomyoma and one rectal carcinoid. All in situ malignant polyps were removed endoscopically with excellent results. There was a high incidence of polyps (13.04%) in group aged 40 49, therefore changes on criteria for initiating routine flexible sigmoidoscopy must be considered. FOB tests (guaiac) showed a very low specific rate for diagnosis since only 24 out of 276 polyps bearing patients showed positive results, probably due to the fact that most polyps were non-ulcerating and small lesions. One third of the total polyps were out of the reach of the rigid scope and this procedure should be excluded in all screening programs of this type. Endoscopic polypectomy should be always an early procedure. In order to decrease the number of nondetected right side colonic lesions, non accessible to the 60 cm flexible scope, at time of polypectomy a simultaneous colonoscopy should be performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305113 TI - [Non ulcer dyspepsia, endoscopic gastritis and Helicobacter pylori]. AB - We studied 33 patients with non ulcer dyspepsia and endoscopic gastritis. 21 were female (63.4%) and 12 male (36.4%). Helicobacter pylori (HP) was investigated by gastric mucosal biopsy. Urease test, Gram, culture, and histology were performed in all and two or more of these test hat to be positive to consider HP infection. 16/33 resulted HP positive (48.8%). Erosive gastritis was most commonly associated with H.P. infection (62.5%). This was statistically significant. In all the cases HP positive chronic gastritis was present. 15/16 were active chronic gastritis. Our results suggest that erosive gastritis is most frequently associated with HP infection and non ulcer dyspepsia. PMID- 1305114 TI - [Colorectal cancer. Experience in 120 patients]. AB - The medical records of 120 patients with Colo-Rectal Cancer who were admitted between 1983 and 1990, were reviewed. The clinical, radiologic, epidemiologic, endoscopic and pathologic characteristic were analyzed in all the patients; also their follow up related to Age, CEA, Dukes and treatment. Late stage diagnosis (10.8% of the cases were diagnosed during obstructive episodes, and 48.3% of the cases were Dukes C and D) and the high mortality (34.1% of the patients died within the first year of the diagnosis), are still basic problems to be solved. The high percentage of patients less than 40 years old (25.8%) and the high incidence of rectal localization of the disease (49.1%), must prompt us to attempt to control the disease by means of colonic evaluation in young people with symptoms attributable to Hemorrhoids or Amebiasis. PMID- 1305116 TI - [Carcinoid tumor of the gallbladder]. PMID- 1305115 TI - [Necrotizing amoebic colitis: a fatal complication]. AB - Five cases of necrotizing amoebic colitis are described. The patients were seen at the University Hospital of Caracas during a period of 3 years in the surgical departments. In 3 patients the diagnosis was made preoperatively and antiamoebic treatment was started. Only one patient survived. The clinical manifestations, diagnosis methods and treatment modalities are revised. PMID- 1305117 TI - [Intra-abdominal infection]. PMID- 1305118 TI - [Non-specific duodenitis: an endoscopic and histologic review]. PMID- 1305119 TI - [Current role of oral cholecystography in the age of ultrasonography]. PMID- 1305120 TI - [The critically ill liver: hepatic ischemia]. PMID- 1305121 TI - [The physician-patient relation. Its characteristics and therapeutic value]. PMID- 1305123 TI - Inviability of hybrids between D. melanogaster and D. simulans results from the absence of simulans X not the presence of simulans Y chromosome. AB - Interspecific crosses between D. melanogaster and D. simulans or its sibling species result in unisexual inviability of the hybrids. Mostly, crosses of D. melanogaster females x D. simulans males produce hybrid females. On the other hand, only hybrid males are viable in the reciprocal crosses. A classical question is the cause of the unisexual hybrid inviability on the chromosomal level. Is it due to the absence of a D. simulans X chromosome or is it due to the presence of a D. simulans Y chromosome? A lack of adequate chromosomal rearrangements available in D. simulans has made it difficult to answer this question. However, it has been assumed that the lethality results from the absence of the D. simulans X rather than the presence of the D. simulans Y. Recently I synthesized the first D. simulans compound-XY chromosome that consists of almost the entire X and Y chromosomes. Males carrying the compound-XY and no free Y chromosome are fertile. By utilizing the compound-XY chromosome, the viability of hybrids with various constitutions of cytoplasm and sex chromosomes has been examined. The results consistently demonstrate that the absence of a D. simulans X chromosome in hybrid genome, and not the presence of the Y chromosome, is a determinant of the hybrid inviability. PMID- 1305122 TI - Effect of estradiol treatment on male mice synaptonemal complexes: difference of sensitivity between neonates and adults. AB - The effect of estrogen on pachytene spermatocytes was studied with the assistance of the synaptonemal complex analysis under electron microscopy. Male NMRI mice were injected with estradiol benzoate from birth onwards and allotted to different groups according to the dose administered: 1) three injections of either 12.5 micrograms or 25 micrograms or 50 micrograms on d0, d5 and d10; 2) single injections of 50 micrograms either on d0 or on d5 or on d10; 3) double injections of 50 micrograms on d0 and d5; and 4) daily injection at the dose of 0.5 micrograms/g BW from d0 to d27. Animals were sacrificed on day 28, 60 and 90. Adult male mice were treated daily with E2B (0.5 micrograms/g BW) for one (from d30 to d60) or two months (from d30 up to d90) to test the age-related sensitivity to estrogen. A number of different SC anomalies were observed at each harvest time. Among all the anomalies, pairing failure (asynapsis) was predominant followed in decreasing order of importance by SC breakage (fragmentation of SCs), and heterotelomeric associations resulting either in quadrivalent-like figures or in trivalents. In E2B treated neonates the frequency of SC anomalies, which was less than 2% in controls, varied from 3.6 to 27% of pachytene cells regardless of the harvest time. In E2B treated adult mice, the SC anomalies were rare (< 4%), but significantly different from controls in which the frequency of SC aberrations did not exceed 1% of pachytene cells. The prevalence of anomalies appeared to be independent of the TW decrease. Our observations suggest that estrogens act indirectly on SCs. Different mechanisms of action are discussed. PMID- 1305124 TI - Comparison of lethal mutations of Drosophila melanogaster with D. simulans when detected by the attached-X method. AB - The purpose of this study was to evaluate the attached-X method compared with the standard Basc method, and, using this method, to find out whether the observed differences in genetic polymorphisms are related to differences in lethal mutation rates in D. melanogaster and D. simulans. When EMS-treated Drosophila melanogaster males are mated to untreated attached-X females, a decrease in the progeny sex ratio (male/female + male) is observed due to the induced lethal mutations on the X chromosome. The decrease in the frequency of male progeny were shown as the attached-X index. The expected male number is calculated from the control sex ratio. The difference between the expected and the observed male numbers, expressed as the ratio to the expected male number, defines the attached X index. The index values for various EMS concentrations were compared to the lethal frequencies obtained by the standard Basc method for the same EMS treatments, and gave a highly positive correlation (gamma = 0.993, p < 0.01, d.f. = 2), thus providing an alternative method for evaluation of possible mutagens. The attached-X method was applied to D. simulans, of which natural populations are known to have relatively low genetic variation, and frequencies of the EMS induced X chromosome lethal mutations were estimated and compared with those in D. melanogaster. The results indicate that D. melanogaster is slightly more sensitive in the sperm and spermatogonial stages, but less susceptible in the spermatid stage when compared with D. simulans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305125 TI - Effects on ADH activity and distribution, following selection for tolerance to ethanol in Drosophila melanogaster. AB - Strains of Drosophila melanogaster homozygous for either the AdhF or the AdhS allele were kept on food supplemented with ethanol for 20 generations. These strains (FE and SE) were tested for tolerance to ethanol and compared with control strains (FN and SN). The E strains showed increased tolerance to ethanol both in the adult and in the juvenile life stages. In adults the increase in tolerance was not accompanied by an increase in overall ADH activity. However, there were changes in the distribution of ADH over the body parts. Flies of the FE strain possessed significantly more ADH in the abdomen, compared with FN. Another set of FN and SN populations were started both on standard food and on ethanol food with reduced yeast concentrations. After 9 months ADH activities were determined in flies from these populations which had been placed on three different media: the food the populations had been kept on, regular food and regular food supplemented with ethanol. The phenotypic effects of yeast reduction on ADH activity were considerably, but longterm genetic effects were limited. PMID- 1305126 TI - [Dynamics of morphological and cytochemical changes in the placenta following cadmium chloride intoxication]. AB - The experiments carried out for the study aimed at determining the prenatal sensitivity to cadmium in the aspect of beth morphological and functional condition of placenta. The experiments were carried out on 80 pregnant female rats divided into three experimental groups and a control one. The experimental animals were daily administered, intragastrically, aqueous solution of cadmium chloride, from the 7th to the 19th day of pregnancy, in doses differing between the experimental groups: 2, 10 and 22 mg of CdCl2 per kilogram of body weight, respectively. The animals were decapitated on the 21st day of pregnancy. Placenta sections, besides hematoxylin and eosin staining, were examined for the activity of the following enzymes: succinic dehydrogenase (SDH) E.C.1.3.99.1., lactate dehydrogenase (LDH) E.C.1.1.1.27., NADH-tetrazole reductase (NADH-t.r.), without a catalog number, and their glycogen reaction was checked. The results of the experiments proved cadmium chloride to cause considerable damage to the enzymatic apparatus of placenta, leading to energy deficit in the cells of both the fetal and the maternal part of this organ. The multienzymatic changes observed preceded the morphologic ones by far. PMID- 1305128 TI - [Infection with chlamydia trachomatis among women with infertility treatment]. AB - 68 women with sterility treatment were tested. Among 13 of them (20%) presence of chlamydial antibodies was found. Hormonal profile was estimated. In a group of women with positive serologic reaction increased concentration of prolactin was found. PMID- 1305127 TI - [Examination of activity of certain phosphatases in the placenta of female rats exposed to cadmium]. AB - The enzymatic examinations were carried out to determine, as early as possible, the functional changes in cells of fetal and maternal part of placenta, as well as pointing out those elements which were the most susceptible to cadmium toxic action. The experiments were carried out on 80 pregnant female rats which were divided into three experimental groups and a control one. The experimental animals were daily administered, intragastrically, aqueous solution of cadmium chloride, between the 7th and 19th day of pregnancy, in doses depending on experimental groups: 2, 10 and 20 mg of CdCl2 per kilogram of body weight, respectively, the animals were killed on the 21st day of pregnancy. Placenta sections were determined for activity of adenosinetriphosphatase stimulated by Mg++ ions (ATP-ase Mg++) E.C.3.6.1.3., and acid phosphatase (AcP) E.C.3.1.3.2. When administered to pregnant females, cadmium chloride was proved to cause a considerable impairment of active transport through biological membranes in placenta, which is indicated by a decrease of reactivity to Mg++ ions stimulated ATP-ase; and an increase in intracellular catabolic processes, which in turn is shown by an increase in reactivity to acid phosphatase. The fetal part of the placenta proves to be more susceptible to the lesion causing activity of cadmium than the maternal part of this organ. PMID- 1305129 TI - [Zinc concentration in human semen of men from childless marriages]. AB - Zinc concentration in human semen was studied on the material of 106 male patients aged 20-35, from childless marriages. Full microscopic examination was performed including number of spermatozoa mobility, flux time, pH, morphological composition, number of leucocytes. Zinc level was measured using spectrophotometric analysis. Trial of relation estimation between zinc concentration and number of live spermatozoa and pH of the semen was taken out. Any significant differences between zinc concentration in the semen from normospermic and oligospermic males were found. There was proved, that semen pH increase was correlated to zinc concentration decrement in the semen fluid. PMID- 1305130 TI - [Levels of ferritin and iron in women with leiomyoma of the uterus treated surgically]. AB - The aim of the work were changes of serum ferritin and iron concentrations in women with leiomyoma of the uterus treated surgically. We took the growth of the leiomyomatous uterus under concern. We observed the lower serum ferritin and iron concentrations before the surgical treatment, and the correlation with the growth of the leiomyoma. The results show that surgery for leiomyomatous uterine contributes significantly for the increase of the serum iron and ferritin in patients. PMID- 1305131 TI - [Levels of catecholamines and activity of the renin-aldosterone system in women with hypertension in the period before and after menopause]. AB - The examinations were carried out for 93 selected women divided into premenopausal group and the group in the early stage of postmenopausal period. Each of these groups was subdivided into two subgroups with normal blood pressure and arterial hypertension. The catecholamine level were determined fluorimetrically as per Euler and Lishajko, and the level of dopamine in plasma using Nagatsu's method. Angiotensin I and aldosterone concentration in serum was determined by radioimmunoassay using RIA set of Sorin. Free catecholamine excretion with urine for women with arterial hypertension in the premenopausal period is highly statistically (p < 0.001), and in the postmenopausal period only epinephrine is statistically higher (p < 0.01), whereas the dopamine level in plasma is smaller, statistically significant only in premenopausal period (p < 0.05). Also for women with the arterial hypertension compared with the control group the angiotensin I and aldosterone concentration in serum is statistically smaller. PMID- 1305132 TI - [Level of estrogen receptors (ER) as a function of histological malignancy stages of tumors in patients with breast neoplasm]. AB - The presence of estrogen receptors (ER) has been studied in 70 patients with primary operable breast cancer. The tumors were graded histologically according to Bloom and Richardson criteria. A significant correlation was found between these two prognostic factors: the better--differentiated tumors (I + II histological grade) had significantly higher level of ER than that in the poor- differentiated tumors. Estrogen receptor content of primary breast cancer as a function of tumor grade can be useful in selection of the most efficient treatment modalities for individual patients. PMID- 1305133 TI - [EPH gestosis or hypertension induced by pregnancy?]. AB - The use of the term "pregnancy induced hypertension" is connected with the use of diagnostic criteria and classification to which this term belongs. These diagnostic criteria have important disadvantages: 1) only diastolic blood pressure is taken into account, 2) oedema is not taken into account, 3) there are only two severity grades, based only on the diastolic blood pressure, 4) "eclampsia imminens" does not exist, 5) "preeclampsia" is when there is elevated diastolic blood pressure and proteinuria, even of low severity both, other symptoms are not taking into account. The applying of such diagnostic criteria can contribute to inadequate management. PMID- 1305134 TI - [Ectopic spleen in pelvis minor--a case report]. AB - A case of ectopic spleen diagnosed as a left adnexal tumor in a 19 year old female was presented. Considering the rareness and lack of typical symptoms, diagnosis of this pathology still is very difficult, and establish most often intraoperatively. In every case of ascertainment irregular mass in minor pelvis one should differentiate it among: colonic diverticulosis, wandering kidney, coproliths, colon and mesentery tumors and ectopic spleen. We consider that ultrasonography plays the special role in these cases. In every case of stating the pathologic structure in minor pelvis it seems advisable not to content only with estimation of genital organs, but also locate such as: kidneys, liver, spleen. Such a procedure allows to state preoperative diagnosis more precisely. PMID- 1305135 TI - Laser video-laparoscopic colpopexy. AB - Video-laparoscopic colpopexy is an innovative procedure. This study included 15 post-hysterectomy with vaginal prolapse. The surgical technique has been described in detail. PMID- 1305136 TI - [Certain factors of cellular immunity in clinical evaluation of women with EPH gestosis symptoms]. AB - The applicability of clinical examination was studied in women with symptoms of medium-advanced or advanced primary gestosis of subpopulation of T lymphocytes (CD3+, CD4+, CD8+) in the peripheral blood. Also studied was the usefulness of the proliferative activity of lymphocytes in in vitro cultures: spontaneous and mitogenic (PHA, ConA, PWM)--in the environment of fetal calf serum (FCS) and autologous sera: heat-inactivated and heat-non-inactivated. It has observed that the percentages of particular T Lymphocyte subpopulations and the proportion of CD4+ lymphocytes to CD8+ lymphocytes in the peripheral blood and the mitogenic activity of the heat-non in activated autologous serum in the test of lymphocyte spontaneous blastic transformation reveal a correlation with an enhancement of particular clinical symptoms of EPH gestosis and with the birth condition of newborns. PMID- 1305137 TI - [Spontaneous proliferative activity of lymphocytes in normal and EPH gestosis complicated pregnancy]. AB - The spontaneous proliferative activity of lymphocytes and CD4+/CD8+ ratio has been estimated in normal and EPH gestosis-affected pregnancy; also the effects of autologous and allogenic sera on this lymphocyte activity was evaluated. Although in normal pregnancy there was a very low CD4+/CD8+ ratio, the spontaneous proliferative activity of lymphocytes and the effects of autologous sera exerted thereupon were the same in either healthy pregnant women or in non-pregnant controls, what indicates a normal cellular immunity in physiological pregnancy. In gestosis an increased proliferative activity of lymphocytes and very high CD4+/CD8+ ratio was observed, when referred to non-pregnant controls. The serum of normal pregnant women did not reveal any immunosuppressive features against the activity of both autologous lymphocytes and gestosis--affected pregnancy, whereas it clearly inhibited the lymphocyte proliferation in non-pregnant controls. A different model of the autologous sera effects on the lymphocyte activity in gestosis women--when compared with the other examined women--is an evidence for altered immuno-modulating parameters of the serum in question. PMID- 1305138 TI - [Use of vancomycin in treating staphylococcal septicemia in newborns]. AB - The authors report the results of vancomycin treatment of staphylococcal septicemia in 26 newborns, including 17 prematures and 9 full-term. It was found, that all coagulase-negative strains and 91% of Staphylococcus aureus were sensitive to this antibiotic. Complete cure in 65% and clinical improvement in 10% were obtained. Death (12%) in very low birth weight prematures were due to secondary complications of septicemia, congenital malformations and intracerebral haemorrhages. Administration of vancomycin in generally accepted doses caused no side effects and is worth in newborns, in which other antibiotics has been given unsuccessfully. PMID- 1305139 TI - [Changes of lipid and lipoprotein levels in serum of women in the early postoperative period after surgical castration]. AB - Concentration of lipids and lipoproteins was estimated in the serum of 26 women after surgical menopause. Different range of changes in concentration of lipoproteins was noticed. First, decreasing levels of concentration of lipo- and lipoprotein fractions was confirmed, and then, their increasing levels in the end of the research period. PMID- 1305140 TI - [Effect of immunotherapy on the level of immunoglobulin in serum of women with pruritus of the vulva]. AB - This study was performed in 52 women in their early postmenopausal period, divided into two equal groups. The control group included women with menopausal symptoms only, women in the study group demonstrated also pruritus. All women were on estrogen replacement therapy, additionally a bacterial auto-vaccine was administered in the study group. The level of IgG, IgA, IgM was determined by radioimmunodiffusion, IgE with an immunoenzymatic method. It was found that women with pruritus of the vulva had lower levels of IgG and IgM and higher levels of IgA and IgE, as compared with the control group. The auto-vaccine caused a significant (p < 0.05) increase of IgG and IgM and significant (p < 0.05) decrease of IgA and IgE, as compared with initial values. PMID- 1305141 TI - [Role of second-look operations in women with ovarian cancer in complete remission]. AB - Among 142 women with ovarian cancer, a complete remission was observed in 51 cases. The second-look operation was performed in 26 cases among them. The operation had no significant influence on 3 and 5 years survivals together. The operation should not be performed in early stages of cancer particularly in mucinous and endometrioid carcinoma. Relapses are observed more frequently and in a shorter period of time in women on whom the second-look operation was not performed. Then it leads to deaths of the women more quickly. PMID- 1305142 TI - [Mastopathy--its hormonal conditions and therapy]. AB - The hormonal factors contributing to the development of benign breast diseases are discussed. The main elements of hormonal therapy of mastopathy are presented. PMID- 1305143 TI - [Post-graduate education in gynecology and obstetrics in the Medical Center of Post-Graduate Education--selected matters]. PMID- 1305144 TI - [Video-laparoscopically modified hysterectomy with vaginal vault suspension]. AB - Thanks to advanced operative techniques to traditional indications for operative laparoscopy, such as: adhesion lysis, endometriosis center coagulation, biopsy, myomectomy, hysteropexy, colpopexy, ovarian wedge resection and biopsy, pelvic herniorrhaphy, aspiration of cystic fluid it can be add laparoscopic treatment of ectopic pregnancy, adnexal tumors, polycystic ovary drilling and endoscopic hysterectomy. However, so complex a surgery necessitates in having an experienced surgical team and the state of art equipment. For the first time in Europe a 32 year old woman was subjected to video-laparoscopic modified hysterectomy with vaginal vault suspension, what was described in this paper. PMID- 1305145 TI - [Video-laparoscopic treatment of polycystic ovaries using monopolar electrocoagulation]. AB - A 27 year old woman with resistant polycystic ovaries was under medical treatment for one year. After that time video-laparoscopic drilling of ovaries with monopolar coagulation was performed. PMID- 1305146 TI - Strengths and needs of black grandparents. AB - This study was conducted to identify ethnic differences in grandparent performance and effectiveness so that an educational program called Becoming A Better Grandparent could be adapted to maximize its relevance for Black families. MANOVA procedures were used to compare perceptions of 204 Anglo grandparents and 204 Black grandparents as well as 175 Anglo and 295 Black grandchildren. Black grandparents perceived themselves more favorably than did Anglos on every subscale of the Grandparent Strengths and Needs Inventory. Black grandchildren assigned grandparents significantly more favorable ratings for teaching and overall success, whereas Anglo grandchildren assigned their grandparents higher scores for coping with difficulty, managing frustration, and meeting information needs. Analyses of grandparent responses revealed significant main effects for age of grandparent, age of grandchild, time spent together, and geographical proximity. Grandchildren responses yielded significant main effects for age of grandchild and time spent together. Findings showed interaction effects for ethnicity by age of grandparent, ethnicity by age of grandchild, and ethnicity by distance. Implications for modifying the program to fit Black grandparents were identified. PMID- 1305147 TI - Patterns of experienced aging with a Finnish cohort. AB - A cohort study of eighty-year old residents in Jyvaskyla (pop. 66,000), central Finland, was carried out in 1990 as part of the EVERGREEN-project. A total of 262 persons born in 1910 were interviewed in the cohort study. The survey data produced a fairly accurate picture of the respondents' objective situation. In order to shed further light on how the respondents felt about growing old, tape recorded narrative stories were collected from a subsample of twenty persons (10 women and 10 men). The stories revealed the subjective meanings and evaluations attached by the individuals concerned to their own aging. Being members of the same culture and the same age cohort, they also shared the same way of perceiving themselves and the surrounding world. It became obvious that there existed some kind of boundary conditions for the experience of aging. The model of boundary conditions for the experience of aging was developed on the basis of the narratives. PMID- 1305148 TI - Motivational goal objects in later life. AB - With a sentence completion technique, 708 elderly participants (64 to 90 years of age) expressed 15,020 personal aspirations. These goals were classified according to their motivational content in ten major categories and their relationships with different sociodemographic variables were studied. Two goal profiles emerge from this analysis. Aspirations centered on self-preservation are associated with very old age, functional impairment, lower S.E.S. and education, being alone or institutionalized. Aspirations of self-development and interpersonal relationships are associated with younger age, physical autonomy, higher S.E.S. and education, being married or living at home. Development of meaningful personal goals are discussed as a mean of intervention with elderly individuals. PMID- 1305149 TI - Joyce Carol Oates' "A theory of knowledge". AB - This article presents a critical reading of "A Theory of Knowledge" by Joyce Carol Oates, which appears in a recently published collection of stories about aging. The story is analyzed in terms of two ideas in current adult developmental theory, the idea of personal narrative as developed by Cohler, and the idea of generativity as developed by Erikson, Kotre, and McAdams. PMID- 1305150 TI - The autobiographical group: a tool for the reconstruction of past life experience with the aged. AB - From a personal construct point of view, writing autobiographical texts becomes a relevant therapeutic ingredient for elderly individuals. If conducted in a context of a group, as Birren proposes [1, 2]; it promotes self-awareness, self disclosure, and the capacity of generating alternative views of life's experiences. In a group of elderly volunteers from a recreational society of Barcelona (Spain), the guided autobiography method was used to foster the reconstruction of the participant's past life experiences. The degree of reconstruction was assessed through a design that included the administration of a repertory grid at the initial and tenth (last) session. A parallel assessment was applied to a control group of participants with similar demographic characteristics. An adaptation of the method proposed by Feixas for the analysis of autobiographical texts was used to assess the assigned writings of the participants for each session. Results show a significant and gradual change in the construing system of those participants in the autobiographical group. Thus, the distance of the elements self-ideal/self and self-ideal/others significantly decreased in comparison to the control group. It is suggested that the guided autobiography is an adequate therapeutic tool to promote the reconstruction of experience in aged individuals. PMID- 1305152 TI - Guided tissue regeneration around dental implants in immediate and recent extraction sites: initial observations. AB - Guided tissue regeneration, the principle of using membranes to exclude epithelial tissue during wound healing, thus enhancing periodontal regeneration, is an exciting addition to the implant armamentarium. However, additional clinical review of the results, advantages, and disadvantages of guided tissue regeneration is necessary before the procedure can be recommended for routine use. To this end, the author reports three representative cases in which membranes were used to encourage healing and discusses the results and problems. PMID- 1305151 TI - An observational study of intergenerational activities and behavior change in dementing elders at adult day care centers. AB - This study investigated whether dementing adult day care clients demonstrate consistent positive behaviors (i.e., eye contact, smiling, attentiveness, etc.) during structured, weekly activities with young children that these adults do not demonstrate during similar activities when the young children are not present. The study built on a preliminary informal study conducted in conjunction with an intergenerational adult day care project. Participants for the study were twenty one adult day care clients who have behavioral characteristics of Alzheimer's or related disorders. The study involved five consecutive weeks of planned, structured music activities prepared by a musical therapist as part of the regular intergenerational activities of the adult day care center. The same activities were repeated twice in the same day at each site, once with children present and once without them present. Two fixed videotape cameras recorded client behaviors in three-minute segments. Scoring was completed by trained, "blind" scorers. The scorers tallied positive behaviors by individuals for randomly selected ten-second segments of the taped intervals. Sessions with and without children were compared using non-parametric tests. Categories of behaviors were compared and specific observed behavioral changes were reported. PMID- 1305154 TI - The immediate implant: bone preservation and bone regeneration. AB - This paper demonstrates that an intact extraction socket is not necessary for the successful integration of a titanium implant fixture. Several case reports are used to describe the immediate placement of fixtures into compromised sockets, some in conjunction with bone grafting and/or guided tissue regeneration techniques to enhance the surgical result. Advantages of immediate implant placement are threefold: (1) treatment time is significantly reduced; (2) ridge contour can be preserved; and (3) it is possible to place the fixture in a more ideal axial position, thus enhancing fabrication, esthetics, and biomechanics of the subsequent restoration. PMID- 1305153 TI - Influence of low-viscosity liners on the retention of three luting materials. AB - A number of materials are available to protect the pulp from postoperative sensitivity. The effect of a calcium hydroxide liner and a dentinal desensitizing agent (potassium oxalate) on crown retention was investigated. Gold crowns were cemented on standardized crown preparations with zinc phosphate cement, glass ionomer cement, or one of two resin cements. A tensile force was applied until separation occurred. The mean applied force at rupture varied greatly among the groups, indicating that the pulpal protection agent may have a distinct effect on the retention of cast restorations. In addition, other clinical factors, such as angle of convergence, crown height, and total surface area of the tooth should be considered. PMID- 1305155 TI - The effect of citric acid application on periodontally involved root surfaces. 1. An in vitro light microscopic study. AB - This study investigated the effect of citric acid application on periodontally involved root surfaces. Forty periodontally involved teeth were randomly divided into four groups of ten teeth each: no treatment, citric acid treatment, root planing alone, and root planing in conjunction with citric acid treatment. Ten nondiseased, untreated teeth served as controls. After treatment, each tooth was split along its long axis; half was examined under light microscopy and half under scanning electron microscopy (part II of the paper). Light microscopy revealed that the effects obtained by scaling and root planing were not altered after citric acid application. Moreover, the cementum layer was not entirely removed without careful and thorough planing of the root surface. Citric acid application alone had no effect on the diseased root surface. Citric acid did not penetrate the dentinal tubules, nor did it alter the collagen content of the roots obtained by scaling and root planing. PMID- 1305156 TI - Formation of new periodontal attachment apparatus after experimental root isolation with collagen membranes in the dog. AB - This study evaluated the ability of collagen membranes to act as biodegradable barriers that interfere with colonization of the root surface by gingival cells and allow selective repopulation of the denuded root surface by periodontal ligament-derived tissue. Over a 3-year period, experimental and control surgical procedures were performed on canine teeth in six beagle dogs and on premolars in three beagle dogs. Results showed that the membranes partially prevented apical migration of epithelium during healing. Regeneration of new cementum, alveolar bone, and periodontal ligament-like tissue was found in the studied premolars but notably absent on the canines. PMID- 1305157 TI - [Health administration: nurses are underpaid]. PMID- 1305158 TI - [Living with handicaps--maintaining dialysis and was diagnosed as diabetes]. PMID- 1305159 TI - [Patients of Orthopedic Department of Tokyo Univ. Hospital--lovers of young patient]. PMID- 1305160 TI - [How can we organize home health care systems to meet community needs]. PMID- 1305161 TI - [Status and awareness of assistant nurse students--facts about assistant nurse students]. PMID- 1305162 TI - [Care for the elderly now available from visiting nurse service agencies]. PMID- 1305163 TI - [A midwife in Paraguay--we saw Yguazu fall from Argentina and Brazil]. PMID- 1305164 TI - [Women support the aging society]. PMID- 1305165 TI - [Ward supervisors. Nurses can share feelings with patients and their families]. PMID- 1305166 TI - [Ward supervisors. My design of home health services for the elderly]. PMID- 1305168 TI - [Ward supervisors. Preparing good working environment for ward staff]. PMID- 1305167 TI - [Ward supervisors. Provision of care efficiently and effectively]. PMID- 1305169 TI - [Ward supervisors. Nurses change, patients change, and then wards change in psychiatric ward]. PMID- 1305170 TI - [Association of Medical Doctors for Asia held AIDS conference--prevention of AIDS is becoming an urgent problem in Japan]. PMID- 1305171 TI - [Letter from Alabama--attendants in Japanese hospital and nurses' aides in Alabama]. PMID- 1305172 TI - [What is pain? Pain clinical]. PMID- 1305173 TI - [Medical topics: husbands have a hard time accepting death of their wives]. PMID- 1305174 TI - [Patients of Orthopedic Department of Tokyo Univ. Hospital--excellent post operative care by a beautiful wife]. PMID- 1305176 TI - [Health administration: problems that need time to be solved]. PMID- 1305177 TI - [Living with handicaps--painful experiences at hospital]. PMID- 1305175 TI - [A midwife in Paraguay--cold tea and afternoon sleep in summer]. PMID- 1305178 TI - [Letter from Alabama--Medicaid and Medicare]. PMID- 1305179 TI - [Years of rehabilitation in hospital after spinal injury--coming back home and making up for long absence from home]. PMID- 1305181 TI - [The Japan Society of Neonatal Nursing established]. PMID- 1305180 TI - [Recent trend in nursing research--on nursing care of working women aged 35 to 64]. PMID- 1305182 TI - [Estimated demand and supply of nursing personnel 1991-2000. Division of Nursing, Ministry of Health & Welfare]. PMID- 1305183 TI - [JNA information: building identity and dignity by individual nursing personnel]. PMID- 1305184 TI - [Elderly couples living on their own are so vulnerable that they need constant attention and care]. PMID- 1305185 TI - [Assisting disabled elderly people to live to the best of their abilities. Psychology of the disabled elderly and assistance to them]. PMID- 1305186 TI - [Assisting disabled elderly people to live to the best of their abilities. Our efforts to make our inmates lively and happy]. PMID- 1305187 TI - [Assisting disabled elderly people to live to the best of their abilities. Music therapy for the elderly with dementia at Belland General Hospital in Osaka]. PMID- 1305188 TI - [Assisting disabled elderly people to live to the best of their abilities. Recreational activities in a rehabilitation hospital ward]. PMID- 1305189 TI - [Assisting disabled elderly patients to live to the best of their abilities. Improvement of quality of life of disabled patient in hospital]. PMID- 1305190 TI - [Report of the JNA Committee on Preparation of Nurse Managers]. PMID- 1305191 TI - [Status and awareness of assistant nurse students--employment and working conditions]. PMID- 1305192 TI - [What is pain? Nursing care after asterisk nerve block]. PMID- 1305193 TI - [Medical topics: how people endure pain seems to differ depending on race and culture]. PMID- 1305195 TI - [Health administration: full time equivalency; lowering of medicine rate]. PMID- 1305194 TI - [Patients of Orthopedic Department of Tokyo Univ. Hospital--night nurses had a busy time with his call "Help me, nurse!"]. PMID- 1305196 TI - [Living with handicaps--I have decided to share with my colleagues "my precious treasures" I got from my handicaps with great sacrifice]. PMID- 1305197 TI - [Letter from Alabama-patient classification system at Alabama University Hospital]. PMID- 1305198 TI - [Years of rehabilitation in hospitals after spinal injury--difficulties of living at home with small children and a mother-in-law]. PMID- 1305199 TI - [Recent trend in nursing research--on care of patients with pain]. PMID- 1305200 TI - [The excerpt from the Amendment of Reimbursement for Social Insurance Medical Fee]. PMID- 1305201 TI - [Building collaborative relationship between welfare care provider and nursing personnel--review of curriculum for welfare care provider]. PMID- 1305202 TI - [From organ transplants to man-made organs]. PMID- 1305203 TI - [Pitfalls of thinking that "I am familiar with this condition". Careful observation at the time of admission cannot be overemphasized]. PMID- 1305204 TI - [Pitfalls of thinking that "I am familiar with this condition". Lessons I learned from my failures]. PMID- 1305205 TI - [Pitfalls of thinking that "I am familiar with this condition". Previous success does not necessarily apply to the next case]. PMID- 1305206 TI - [Pitfalls of thinking that "I am familiar with this condition". Communication failures--gaps between knowledge and practice]. PMID- 1305207 TI - [Pitfalls of thinking that "I am familiar with this condition". Why the menthol compress]. PMID- 1305208 TI - [Pitfalls of thinking that "I am familiar with this condition". The cases I could treat otherwise]. PMID- 1305209 TI - [Status and awareness of assistant nurse students--irregular working hours and days off]. PMID- 1305210 TI - [What is pain? Nursing care after extradural star-shaped nerve block]. PMID- 1305211 TI - [A midwife in Paraguay--hot Christmas and New Year]. PMID- 1305212 TI - [Medical topics: trying to understand what is behind patients' words]. PMID- 1305213 TI - [Expecting mothers who visit my clinic--abortion experience had left her with anxiety and guilt feeling]. PMID- 1305214 TI - [Health administration: what is the policy of the Amendment of the Reimbursement of the Medical Fee?]. PMID- 1305215 TI - [Letter from Alabama--lawsuits on medical malpractice]. PMID- 1305216 TI - [Consideration on the Japanese title for "nurse"--a proposal to change it to a new one which can be used regardless of gender. Students of Tokyo Metropolitan Otsuka Nursing School]. PMID- 1305217 TI - [Recent trend in nursing research--my research works were started from clinical questions]. PMID- 1305218 TI - [Caring as the infrastructure of the aging society]. PMID- 1305219 TI - [Outline of the bill for promotion of securing nursing resources]. PMID- 1305220 TI - [Reimbursement for nursing fee given the highest increase for the first time in history]. PMID- 1305221 TI - [The excerpt from the Amendment of Reimbursement for Medical Fees--reimbursement for medical fee for the aged]. PMID- 1305222 TI - [The Amendment to the Health for the Aged Law--the system of visiting nurse service for the elderly to start from April]. PMID- 1305223 TI - [Directors of nursing report quality care made possible at their small-scale hospitals. A 100-bed hospital providing standardized nursing care and visiting nurse service]. PMID- 1305224 TI - [Directors of nursing report quality care made possible at their small-scale hospitals. Patient-centered hospital specializing in circulatory diseases]. PMID- 1305225 TI - [Directors of nursing report quality care made possible at their small-scale hospitals. Patients and families are known to the staff by name in our geriatric hospital]. PMID- 1305226 TI - [Directors of nursing report quality care made possible at their small-scale hospitals. Nurses are members of various committees]. PMID- 1305227 TI - [Directors of nursing report quality care made possible at their small-scale hospitals. Good communication among staff and with administration has produced good work environment]. PMID- 1305228 TI - [Directors of nursing report quality care made possible at their small-scale hospitals. A hospital funded by the community people and serving for the community]. PMID- 1305229 TI - [What is pain? Pains experienced by cancer patients at the terminal stage]. PMID- 1305230 TI - [Expectant mothers at my clinic--"moratorium"-type persons]. PMID- 1305231 TI - [A midwife in Paraguay--Indian children]. PMID- 1305232 TI - [Medical topics: loss of subject and grief reaction]. PMID- 1305233 TI - [Living with handicaps--precious things left for me after I loft most of the things]. PMID- 1305234 TI - [Health administration: further amendment needed for reimbursement for medical fee]. PMID- 1305235 TI - [Status and awareness of assistant nurse students--they perform almost the same jobs as RNs]. PMID- 1305236 TI - [Letter from Alabama--visiting nurse service and hospice home care at Alabama University Hospital]. PMID- 1305237 TI - [Years of rehabilitation in hospital after spinal injury--a timid spoiled girl grew to live a challenging life]. PMID- 1305238 TI - [I am grateful to Linda for her strict patient education after I received the liver transplant in the U.S]. PMID- 1305239 TI - [Relief activities for the victims of Unzen volcanic eruption at the Shimabara Hot Spring Hospital]. PMID- 1305241 TI - [Florence Nightingale: her personality, her words. Her journey to Egypt and Greece at the age of 30--and she decided to do nursing]. PMID- 1305240 TI - [Florence Nightingale: her personality, her words. Exploring the origin of nursing through the works of Florence Nightingale, mainly "Notes on Nursing"]. PMID- 1305242 TI - [Florence Nightingale: her personality, her words. "Careless and insensitive nurse" in "Notes on Nursing"]. PMID- 1305243 TI - [Florence Nightingale: her personality, her words. Her "Three-fold interests" directs my nursing practice]. PMID- 1305244 TI - [Florence Nightingale: her personality, her words. Most impressive statements in "Notes on Nursing"]. PMID- 1305245 TI - [Florence Nightingale: her personality, her words. Encouraged by the messages from Nightingale]. PMID- 1305246 TI - [Florence Nightingale: her personality, her words. Respect for life is the mission of nursing]. PMID- 1305247 TI - [Florence Nightingale: her personality, her life. Importance of observation of "not doing well"]. PMID- 1305248 TI - [Florence Nightingale: her personality, her words. Difficulties of psychological support]. PMID- 1305249 TI - [Medical topics: how about taking patients on beds into washing rooms to protect their privacy]. PMID- 1305250 TI - [A midwife in Paraguay--sand fleas and other harmful insects]. PMID- 1305251 TI - [Health administration: reexamination of phenomena that are "taken for granted"]. PMID- 1305253 TI - [Years of rehabilitation in hospital after spinal injury--I realized that I am made to live by the people who assist me]. PMID- 1305252 TI - [Letter from Alabama--nursing education at Alabama University]. PMID- 1305254 TI - [Use of high-tech equipment in aging society]. PMID- 1305255 TI - [Recent trend in nursing research--qualitative analysis of nursing activities in clinical settings]. PMID- 1305256 TI - [Daily activities of female patients]. PMID- 1305257 TI - [Report on perception of graduates and students of jr. colleges of medical technology of national universities concerning upgrading of colleges to baccalaureate programs]. PMID- 1305258 TI - [Safe handling of cytotoxic drugs. Cytotoxicity and principles of safe handling]. PMID- 1305259 TI - [Safe handling of cytotoxic drugs. Cytotoxic drugs and safe handling]. PMID- 1305260 TI - [Safe handling of cytotoxic drugs. Researches and guidelines on safe handling of cytotoxic drugs in the U.S]. PMID- 1305261 TI - [Safe handling of cytotoxic drugs. Work practice for personnel dealing with cytotoxic drugs]. PMID- 1305262 TI - [Crisis of nursing in Japan-quantity, quality and professionalism of nursing are endangered]. PMID- 1305263 TI - [Status and awareness of assistant nurse students--financial assistance, loans and obligation to work after finishing school]. PMID- 1305264 TI - [Expectant mothers at my clinic--alcohol and smoking]. PMID- 1305265 TI - [Getting old and thinking hard--how to die?]. PMID- 1305266 TI - Disabilities Act and AIDS. PMID- 1305267 TI - Observations. PMID- 1305268 TI - 100 percent smokefree New Jersey restaurants. AB - The overwhelming majority of New Jerseyans are not smokers and they want and deserve protection. Smokefree policies benefit restaurants. Smokers, too, support controls. Legal action, education, and public demand will make New Jersey restaurants smokefree. PMID- 1305269 TI - Treatment of hepatic metastases from colorectal origin. AB - Currently, chemotherapy for hepatic metastatic disease is palliative at best. However, successful resection of hepatic metastatic deposits from colorectal origin demonstrates a five-year survival, approaching 60 percent in selected cases. PMID- 1305270 TI - New Jersey's case for local control of the Medicare review process. AB - The government is launching a program called the Health Care Quality Improvement Initiative (HCQII). The government plans to reposition PROs as educational rather than judgmental entities. The PRO of New Jersey, Inc. urges physicians to oppose regionalization of the screening process. PMID- 1305271 TI - The response of restaurants to New Jersey's smoking control law. AB - The authors surveyed a representative sample of New Jersey restaurants to determine what provisions were made for patron smoking, and whether the restaurants were in compliance with the state law intended to restrict smoking in restaurants. The authors report the results of their recent study. PMID- 1305272 TI - Infectious disease rounds: Pott's puffy tumor with intracranial complications. AB - Pott's puffy tumor, a complication of frontal sinusitis, frequently is associated with intracranial infection. Early diagnosis can be obtained by computed tomography. Treatment should include surgical drainage and antibiotic therapy directed against mixed aerobic and anaerobic pathogens. PMID- 1305273 TI - MSNJ Auxiliary: responsibility on water. AB - The Medical Society of New Jersey Auxiliary kicked off its Responsibility on Water program. Designed and planned by MSNJA President Marion H. Geib, the program is intended to make children and adults aware of the deadly mix of alcohol and water activities. PMID- 1305274 TI - [The toxicity of mercury in amalgam dental fillings]. AB - 1. A survey on the literature concerning the toxicity of amalgam is presented. 2. Opinions from various sources are discussed. It is found that there are no conclusive experimental results of clinical importance. Existing results on adults cannot be applied to children, who are more sensitive to amalgam. 3. Research into the toxicity of amalgam in children has begun. Results are expected later in 1992. PMID- 1305275 TI - [Electrocardiography in pediatrics. 1: Critical considerations of methods and experimental findings]. AB - The results of experimental cardiology are reported on the basis of the electrophysiology of the heart. The QRS complex of the ECG, representing the spread of excitation through the ventricles, is used as an example to reflect the physiological and pathological events of the heart. The limitations of this example arise from the uncorrected recordings of the potential differences from the body surface. The need to use corrected lead systems is pointed out. The most commonly used FRANK lead system is extremely sensitive to the inaccurate positioning of lead points on the thorax. Evidence for this drawback is given by experimental findings in infantile and juvenile rats. It is clear that inaccurate positioning of electrodes is especially crucial in small subjects. A fundamental criticism of the FRANK lead system used in growing subjects is the impossibility of eliminating the errors caused by the changing geometry of the thorax of children of different ages. Improvement of the physical correction of ECG recordings in children for the purpose of reliable diagnostics is vital. PMID- 1305276 TI - [Help for behaviorally disordered children and their families]. AB - 1. A comprehensive survey is given on the divergence of opinions on child education in this century. 2. The aim of this survey is to find out the causes of children's behavioral disorders using psychoanalytical methods. 3. The factors of behavioral disorders occurring in families today are discussed. 4. Conclusions for psychoprophylaxis and -therapy of behavioral disorders of children are drawn. They describe the important roles of parents, pediatricians and psychologists and the social responsibilities of the family of a child suffering from a behavioral disorder. PMID- 1305278 TI - [Circumcision for prevention of penis and cervix cancer? Results of a parent survey]. AB - Results of questioning young parents--582 by direct questioning and 624 by questionnaires--about their knowledge of male circumcision are presented. 61% of those directly questioned and 24% of parents polled by questionnaire did not know what circumcision means. The older the parent and the higher their professional qualifications, the greater their knowledge. Reasons for circumcision were divided into four categories: surgical, hygienic, prophylaxis of cancer and cosmetic. Health education about genital hygiene and circumcision is necessary. PMID- 1305277 TI - [Electrocardiography in pediatrics. 2: Recommendations for a newly introduced recording and evaluation procedure]. AB - ECG recordings were made by means of a modified NELSON-lead system in a total of 100 children aged between 2 weeks and 59 months. Software developed by ourselves served for on-line calculations of the dipole moment D which is graphically represented by vector loops in three projection planes, horizontal, frontal and sagittal. In addition, the maximum spatial vector Dmax and the mean vector A are calculated by the program. The examination of one child including positioning of 20 electrodes and production of a hard-copy of the results takes no longer than 15 minutes. The children were unsedated and awake when the ECGs were recorded. The results show the continuously growing dipole moment and its gradually changing direction from the right posterior or left anterior to the left posterior quadrant in parallel with the growth of the body and the heart, respectively. The smallest vector magnitudes and smallest vector loops of the dipole moment are measured in the youngest infants (0-2 months) while very high voltages in conventional ECGs of infants are regularly seen, predominantly in the precordial region. Two examples of pathological NELSON-ECGs are reported. One case is a boy aged 4 years 10 months with aortic supravalvular stenosis, the other one is a girl aged 4 years 3 months with pulmonic valve stenosis. These cases demonstrate the excellent suitability of this noninvasive method as a diagnostic tool for pediatric cardiology. PMID- 1305279 TI - [Congenital syphilis]. AB - Four infants with Lues connata, three with the early stage of the disease (patients 1-3), are reported. Diagnosis was made after exclusion of other diseases. Initially an infectious disease was expected, since anemia, leucocytosis, thrombocytopenia, hepatomegaly and/or splenomegaly and a bad condition were found. In two patients bone structure was abnormal. Elevated serum concentrations of liver enzymes (ALAT, ASAT) were the indication for liver biopsy in one patient, in whom an accompanying hepatitis was diagnosed. Treatment was performed with penicillin, no JARISCH-HERXHEIMER reaction was observed. The Lues tests were negative during pregnancy but a displacental transfer of pathogenic agents could be assumed. Patient 4 was diagnosed at 9 months of age. Infection of the mother probably occurred in the last 6 weeks of pregnancy. It can not be decided if the baby has a connatal or acquired Lues. The titer decrease of the CMT-test after the end of the penicillin therapy is a marker for a successful treatment. If treatment was started at 2 years of age a total clinical recovery can be expected. The case reports demonstrate that negative Lues test during pregnancy do not exclude Lues connata in newborns. The Lues diagnosis should be considered if an infectious disease in a newborn can not be diagnosed. A general Lues serodiagnostic test is recommended in all newborns before they leave the obstetrics department. PMID- 1305280 TI - Transepithelial potential difference in the bronchial system of children with chronic bronchitis and bronchial asthma. AB - In 45 children with chronic non-specific respiratory diseases (CNSRD), 18 with bronchial asthma and 27 with relapsing or chronic bronchitis, the transepithelial potential difference (tpd) was measured in the tracheobronchial system (bronchoscopy under general anaesthesia). The statistical variation in the tpds was highly significant. In asthmatics with significant eosinophilia in the bronchial secretions of the main bronchus we found a tpd of 26.5 (+/- 8.5) mV and in bronchitics a tpd of 18.2 (+/- 6.3) mV. This suggests that the presence or absence of eosinophils in the secretions, the products of intermediate cell metabolism or different pathogenetic processes, could be responsible for the variety of change in the tpd measured in the respiratory tract. PMID- 1305281 TI - [Results of studies with the Meyer-Probst Encephalopathy Questionnaire in children with normal behavior]. AB - To diagnose encephalitis the 'Encephalitis-Fragebogen (E-F)' by Meyer-Probst is a valid instrument. The authors tested a large number of children without unadaptive or neurotic behaviour (4.5 to 11.9 years) with this instrument to define new standards. Parts of the results are presented. There are very significant differences between boys and girls. Considering the age, different standards are necessary only for boys. Using these new standards it is possible to avoid misinterpretation. PMID- 1305282 TI - [Differential evaluation of a study of children with normal behavior with the Meyer-Probst Encephalopathy Questionnaire]. AB - To define new standards for the 'Enzephalopathie-Fragebogen' by Meyer-Probst the authors tested a large number of children (n = 2841) without unadaptive or neurotic behaviour (4.5 to 11.9 years). The results of the total scale were published in an earlier article. The findings of the specific scales prove significant differences between boys and girls with respect to the scales hyperactivity, social adaption, emotional instability and educability. Considering the age, different standards are necessary for boys only. The results published here differ from those of Meyer-Probst. PMID- 1305283 TI - [Diagnostic and therapeutic aspects of cerebral seizures caused by pseudohypoparathyroidism]. AB - The knowledge of the pseudohypoparathyroidism is of great importance since the consequence of inadequate treatment may be serious. The most important features of the pseudohypoparathyroidism are the hypocalcemia and seizures. The following case concerns a patient with pseudohypoparathyroidism; the clinical symptoms and treatment of this disorder will be discussed. PMID- 1305284 TI - Experience in management of diminished growth in adolescent Turner's syndrome patients. AB - The aim in the management of patients with Turner's syndrome, besides substitution of sexual steroids, is the attempt to improve their final height. The data allow therapeutic recommendations, which, however, realize only the first intention. The final height, indeed, cannot be improved by traditional methods. Further two alternatives remain to be tested: long time low dose estrogen therapy, and high dosed HGH application. PMID- 1305285 TI - The effect of N-acetyl-cysteine (Mucosolvin) on the transmural potential difference of the mucosa in children. AB - The mucosa of the respiratory and gastrointestinal tract produces an active transepithelial (or transmural) electric potential difference (tpd), which can be measured (in millivolts, mV). In CF-children receiving oral N-acetyl-cysteine treatment, the tpd of the buccal mucosa is largely the same as that in non-CF children; the tpd of the nasal mucosa is significantly higher in CF-children. Given orally, N-acetyl-cysteine also provokes a significant decrease in the rectal mucosa tpd in CF-children. We suggest the effect is caused either by an osmotic effect of N-acetyl-cysteine (local), and/or by alteration of the factors regulating basal electrolyte transport/conductance of epithelia (chloride secretion? leaky junction?). PMID- 1305286 TI - Indirect composite resin crowns as an esthetic approach to treating ectodermal dysplasia: a case report. AB - This article presents a case report describing the indirect fabrication of composite resin crowns for the restoration of primary anterior teeth. A 3-year old with a confirmed diagnosis of hypohidrotic ectodermal dysplasia was provided with composite resin crowns that were both esthetic and functional. The indirect method decreases clinical time, provides a durable restoration, and allows treatment of patients who lack the cooperative ability to endure prolonged direct bonding appointments. The indirect technique may be feasible for the restoration of carious teeth as well as the presented case. PMID- 1305287 TI - Glass-ionomer-silver-cermet interim Class I restorations for permanent teeth. AB - Glass-ionomer-silver-cermet cement has proved to be a worthy alternative to silver amalgam for restoring certain Class I lesions in primary teeth. Such restorations are now known to last up to 8 years without need for repair or replacement. Cermet cement has also been used for interim restoration of permanent teeth in special cases, with ideal results. The procedure for placing a glass-ionomer-silver-cermet cement Class I restoration is described. PMID- 1305288 TI - Disocclusion time-reduction therapy with immediate complete anterior guidance development to treat chronic myofascial pain-dysfunction syndrome. AB - Successful treatment of chronic myofascial pain-dysfunction syndrome by disocclusion time-reduction therapy has been shown to be effective in 1 to 3 months, with the major muscular changes occurring in the first 30 to 40 days following initial therapy. Disocclusion time reductions have been previously reported to quickly reduce or eliminate numerous symptoms of chronic myofascial pain-dysfunction syndrome. Proper modification of an existing occlusal scheme from one that contains lengthy disocclusion time to one with short disocclusion time can be accomplished by implementing the method of occlusal adjustment known as immediate complete anterior guidance development. This paper describes the proper clinical occlusal adjustment methodology using a computerized device that shows the measurement and subsequent reduction of excessive disocclusion time. This directly lessens elevated contractile muscle activity, which leads to rapid muscular recovery of the involved dysfunctional muscle groups. PMID- 1305289 TI - Clinical procedures in fabricating post and core restorations: case reports. AB - In this series of case reports, unusual clinical procedures in the implementation of post and core restorations are demonstrated and their difficulties are discussed. First a method for preparing an immediate post and amalgam core, while utilizing the provisional self-curing acrylic resin crown as a matrix for the condensation of amalgam, is presented. The second technique is the fabrication of a cast post and core restoration that fits an abutment root as well as the existing crown of a four-unit fixed restoration. The third case illustrates the clinical procedures involved in preparing an immediate post and core restoration through an opening in the crown, when the extended fixed restoration cannot be removed. PMID- 1305290 TI - Intentional replantation: report of a successful case. AB - Irreversible iatrogenic damage sometimes occurs during dental treatment. In certain cases, intentional extraction, repair, and replantation can be used to save the damaged tooth. This case report describes the successful replantation of a premolar that had sustained a large root perforation. PMID- 1305291 TI - A 3-year clinical study of a hybrid composite resin as fissure sealant and as restorative material for Class I restorations. AB - After 3 years, 78.0% of 64 reexamined fissure restorations (extended sealants) and small occlusal restorations were clinically acceptable or excellent, and 21.9% had to be repaired or replaced because they had fractured (6.3%) or were no longer clinically acceptable by some other criterion (15.6%). The conservative preventive resin restoration seems to be an effective treatment for small occlusal defects. Meticulous dental hygiene by the patient and regular examinations by the dentist are mandatory. PMID- 1305292 TI - Restoration quality in relation to wedge-mediated light channeling. AB - Thirty large mesio-occlusodistal cavities with their margins totally in enamel were restored using the three-sited light-curing technique in five different ways: group 1 = Mark I version of a light-reflecting wedge; groups 2 and 3 = interproximal curing with transparent, nonreflecting wedges; groups 4 and 5, Mark II version of the light-reflecting wedge with increased resiliency. In groups 3 and 5, the light that was not conducted by the transparent wedges was shielded by a piece of aluminum foil. It was found that, when used directly and unshielded, both Mark I and Mark II versions of the light-reflecting wedge induced significantly better marginal adaptation than the transparent, nonreflecting wedge, especially gingiovproximally. With both the nonreflecting and reflecting wedges, the shielding had no effect on the overall percentage of excellent margin. However, gingivoproximally, the shielding significantly improved the marginal quality in the nonreflecting wedge groups, leading to the conclusion that the first increment should be cured as thoroughly as possible from a gingivoproximal direction, preferably indirectly via light-conducting wedges. Direct irradiation from a lingual or buccal direction is less favorable. PMID- 1305293 TI - Effect of peroxide bleaches on resin-enamel bonds. AB - Human third molar teeth were divided into three groups: untreated control; enamel treated with 35% hydrogen peroxide for 2 hours; and enamel treated with 10% carbamide peroxide gel for 14 days. All teeth were ground to present a flat enamel surface, to which cylinders of light-cured composite resin were bonded. Shear bond strengths were determined for each specimen. The mean shear bond strengths of resin-enamel bonds after pretreatment with both 35% hydrogen peroxide and 10% carbamide peroxide were significantly lower than those for untreated controls. External bleaching with these materials prior to resin bonding procedures may reduce the quality of resin-enamel bonds. PMID- 1305294 TI - Biocompatibility of an enamel-dentin adhesive. AB - To assess the biocompatibility of a third-generation dentinal adhesive that uses a smear layer conditioner (Scotchbond 2), Class V cavities were prepared and restored in vivo, following a standardized protocol, in 32 human premolars to be extracted for orthodontic reasons. Histologic observation showed seven slight, five moderate, and one severe reaction short term, while 11 slight and three moderate reactions were observed long term. It appeared that the intensity of the reactions decreased with time. Bacteria were observed on only five teeth, and no correlation could be established between the presence of bacteria and the intensity of the reactions. It seemed that the conditioning of the smear layer, although it might have rendered the residual dentin more permeable, limited percolation phenomena by increasing adhesion. Although only one severe reaction was observed, it is mandatory in a clinical setting to place a protective lining near the pulp. PMID- 1305296 TI - Dentinogenesis imperfecta: a case report. AB - Dentinogenesis imperfecta is a localized form of mesodermal dysplasia of the dentin affecting both the primary and permanent dentitions. Most previous reports on dentinogenesis imperfecta describe treatment with overdentures, which have several disadvantages. The present report describes a case of dentinogenesis imperfecta in an 11-year-old girl. A combination of restorative, prosthetic, and surgical treatment was used to resolve the condition. PMID- 1305295 TI - A formula for disaster: tenure plus the demise of mandatory retirement. PMID- 1305297 TI - Oral amalgam pigmentations (tattoos): a retrospective study. AB - Oral amalgam tattoos are typically asymptomatic, benign, solitary or multiple clinical lesions produced by inadvertent placement of dental silver amalgam restorative material into the oral soft tissues. Diffuse lesions often display a grayish brown discoloration while other tattoos present a darker blue-black contrast. One hundred sixty-eight biopsy reports that confirmed the diagnosis of amalgam tattoo were analyzed to find age, sex, and race of the patients and size, location, and duration of occurrence of the lesions. Among the 168 cases, 235 individual tissue specimens were identified. A majority of the specimens were taken from the buccal mucosa, gingiva, and alveolar mucosa. The most common site for the lesion was the mandibular arch. The size of the individual specimens ranged from 0.10 cm to 1.50 cm. Almost two thirds of the specimens were 0.40 cm or less. PMID- 1305299 TI - Emergency repair followed by complete-coronal restoration of a fractured mandibular incisor. AB - Severely fractured anterior teeth often require immediate repair, while long-term restoration is delayed until a healing period is completed. This paper details a technique of immediate emergency repair of a fractured mandibular incisor followed by placement of a bonded composite resin complete-coronal restoration months later. Careful diagnosis, gentle handling of the freshly traumatized tooth and surrounding tissues, and ideal selection and use of the respective bonding materials are necessary to ensure eventual replication of form, function, and tooth shade when the long-term restoration is placed. PMID- 1305298 TI - Atraumatic surgical technique and implant bed preparation. AB - The issues of bone necrosis and implant bed congruency are both central to the success or failure of endosseous dental implants to achieve osseointegration. Use of internally irrigated drilling instruments has been postulated to minimize bone necrosis. The ability of the cutting instruments to produce a smooth, congruent implant bed and retain fine bone structures is also critical to achieving primary integration. In the experiment conducted, the use of internally cooled instruments reduced the likelihood of thermal bone damage, particularly when trephine mills were used. Trephine mills were able to retain the fine bone structures of the walls of the implant bed site. No visible degradation occurred from multiple uses of the instruments. PMID- 1305300 TI - Prerestorative bleaching: effect on microleakage of Class V cavities. AB - The effect of bleaching extracted teeth on the microleakage of subsequently placed Class V composite resin restorations was evaluated. Ten extracted premolars were stored in water at 37 degrees C to serve as controls. Ten premolars were exposed to a carbamide peroxide gel for three 2-hour periods per day for 9 days. These specimens were stored in water at 37 degrees C except during treatment periods. Class V cavity preparations were then placed at the cementoenamel junction of the facial and lingual surfaces of all teeth. Half of the teeth of each group were restored with Scotchbond 2/Silux Plus and half were restored with Prisma Universal Bond 3/AP.H. After 24 hours of storage in 37 degrees C water, the teeth were thermally stressed for 100 cycles. Microleakage was assessed by dye penetration. The results demonstrated that prerestorative bleaching did not affect the marginal seal of subsequently placed restorations. PMID- 1305302 TI - Effect of eugenol-containing endodontic sealer on retention of prefabricated posts luted with adhesive composite resin cement. AB - Reported studies have implicated eugenol in the reduction in retention of restorations luted with chemically cured composite resin cement. This study investigated the effect of residual eugenol in the root canal on the retention of ParaPost dowels cemented with Panavia EX composite resin. An attempt was also made to identify and to determine the most effective cleansing procedure. Findings of this study demonstrated a substantial decrease in retention of posts luted with Panavia composite resin cement in the presence of eugenol. Irrigation with ethyl alcohol (ethanol) or etching with 37% phosphoric acid gel was found to be effective in restoring the resistance to dislodgment of the posts, but alcohol produced the most consistent and reliable results. PMID- 1305301 TI - Cariostatic and ultraconservative sealed restorations: six-year results. AB - The objective of this clinical study was to determine the ability of an ultraconservative, sealed composite resin restoration, without a traditional cavity preparation and without the removal of the carious lesion, to arrest Class I caries. Tooth preparation was limited to placing a bevel in the enamel. These restorations were compared, over 6 years, with (1) ultraconservative, localized, sealed amalgam restorations with no extension for prevention and (2) traditional, unsealed amalgam restorations with the usual extension for prevention outline form. Caries was arrested by the ultraconservative, sealed composite resin restorations for 6 years. Complete sealant retention on the sealed amalgam restorations was somewhat lower than that on the sealed composite resin restorations; conversely, partial sealant retention was higher for the sealed amalgam group. The marginal integrity of the sealed amalgam restorations was significantly superior to that of the unsealed amalgam restorations. The sealant also protected Class I posterior composite resin restorations against wear. PMID- 1305303 TI - Resistance to fracture of ceramic jacket crowns. AB - The resistance to fracture of jacket crowns, fabricated of cast glass-ceramic and five traditional ceramics, was evaluated. Four identical jacket crowns of each type were constructed on absolutely equal dental abutments in epoxy resin, obtained from a primary mandibular molar. An increasing load was then applied to the mesiobuccal cusp of each of the 24 crowns. Although the glass-ceramic proved to have the highest fracture resistance, it was not significantly stronger than three other traditional ceramics; neither did it seem to be suitable for constructing jacket crowns on posterior teeth. PMID- 1305304 TI - [Cleft lip and cleft palate: cephalometric characteristics of affected individuals, their relatives and a control population]. AB - Eight cephalometric parameters were determined in individuals affected with cleft lip and cleft palate, their parents and siblings and a sample of normal individuals. No differences were found in males in any group. In contrast, affected females had lower measurements than their female relatives, and these lower latter in turn had measurements than control females. Although differences between groups were significant enough overlap existed and therefore genetic counseling based on these measurements would be uncertain. PMID- 1305305 TI - [Concentration of trace elements in children from northern Chile]. AB - Industrial processes may lead to severe alterations of environment affecting the health and quality of life of neighbouring communities. The present study reports the concentrations of Cu, As, Br, Na, K, Se, Hg, Cr, Co, Zn, Fe and Sb in samples of hair from children 6 years of age living in Antofagasta, Chuquicamata, Maria Elena, Calama and San Pedro de Atacama. Results were compared to those obtained in children of the same age living in Santiago. Samples were obtained according to recommendations from the International Nuclear Energy Organization and were analyzed by the neutron activation method at facilities of the Chilean Nuclear Energy Commission. Values for Cu (38.8 ppm), Cr (4.29 ppm) and As (19.2 ppm) in children from Chuquicamata are considered dangerous according to international standards. PMID- 1305306 TI - [Treatment of non-variceal upper digestive hemorrhage with endoscopic thermocoagulation]. AB - Over a year period, 60 of 172 patients presenting with upper gastrointestinal bleeding were treated by endoscopic thermocoagulation. Entry criteria included active bleeding (pulsatile or oozing), a visible vessel, sentinel clot or the presence of a pigmented protuberance at the ulcer crater. Hemostatic therapy was performed using the heat probe. The physical status and risk of the patients was estimated according to the ASA classification. Hemostasis was obtained in 17 of 21 patients with pulsatile bleeding (81%), 30 of 30 patients with oozing (100%) and 18 of 18 patients with a visible vessel or a pigmented protuberance in the lesion (100%). Three patients, older than 70 years of age, died. All had pulsatile bleeding from a deep ulcer located at the posterior-inferior wall of the duodenal bulb. They were classified as ASA III (n = 1) or IV (n = 2) with significant concomitant illness. These results suggest that endoscopic thermocoagulation is an effective treatment of active upper gastrointestinal bleeding, especially useful in a group of high risk patients. PMID- 1305307 TI - [Benign polypoid lesions of the gallbladder. Their relation to gallbladder adenocarcinoma]. AB - Out of 12,153 cholecystectomies performed over a period of 10 years, 114 polypoid lesions were found in 81 removed gallbladders (0.7%). 225 adenocarcinomas of the gallbladder were found in the same population (1.85%). The mean age of patients with polypoid lesions was 46 years, with a male to female ratio of 1:2.7. 94% of lesions measured less than 10 mm and only 9.6% were adenomas. Among these, dysplastic alterations were found in all and one had evidence of early adenocarcinoma. The mean age of patients with adenocarcinoma was 62 years with a male to female ratio of 1:6. Residual adenomas were found in 2 cases and multiple adenomas coexisted in another case. Thus, polypoid lesions of the gallbladder are less frequent than adenocarcinoma. Only adenomas show a potential to evolve to malignant lesions, but their low incidence makes them an unimportant precursor of gallbladder carcinoma. PMID- 1305308 TI - [Clinical course characteristics of gastric cancer 1958-1990]. AB - The clinical, surgical and histopathologic characteristics of patients with gastric cancer were compared among 3 consecutive periods from 1958 to 1990. A significant increase in the frequency of location at the upper third of the stomach, a greater proportion of resectable lesions, an increasing tendency towards extended total gastrectomy and a significant increase in the frequency of undifferentiated or diffuse carcinoma were observed. A change in pathogenetic factors along the years may be involved in the differences described. PMID- 1305309 TI - [Simultaneous digestive and cardiological studies in asymptomatic chagasic patients]. AB - Prognosis in patients with Chagas disease is related to systemic involvement. 43 asymptomatic chagasic subjects, 28 males and 15 females aged 28 to 85 years, were subjected to electrocardiograms and upper and lower gastrointestinal radiological studies. 23 patients (53%) had evidence of involvement of at least one organ. Multiple involvement was demonstrated in 5 individuals (12%): one patient had megaesophagus, megacolon and abnormal EKG; 2 had megaesophagus and abnormal EKG; 1 had megaesophagus and dolicocolon and 1 had dolicocolon and abnormal EKG. Dilated esophagus was found in 6 patients (14%), dolico or megacolon in 13 (20%) and abnormal EKG, mostly bifascicular block in 10 (23%). Thus, isolated or multiple organ involvement is frequent in asymptomatic chagasic subjects. Routine screening of this population is advisable for early diagnosis and prevention of complications. PMID- 1305310 TI - [Echotomographic findings in gastric cancer]. AB - Echotomographic studies were performed in 163 patients with gastric cancer from 1984 to 1990. The technical aspects of the examination and the images obtained in different lesions are described. Emphasis is placed on local or diffuse wall infiltration, ulcerations, vegetations or stenotic lesions. Consideration of these aspects during routine echotomographic exploration of the abdomen may help improve to the detection of gastric cancer. PMID- 1305311 TI - [Gastric cancer: epidermal growth factor and epidermal growth factor receptor]. AB - In 19 patients with advanced gastric cancer the expression of epidermal growth factor receptor and epidermal growth factor (EGF) were studied using immunohistochemical techniques. There were 12 males and the mean age of the group was 54.8 years. Most cases belonged in Borrmann's types III or IV. Tumoral cells were positive for EGF receptor in 9 patients (47%), with a strong reaction in 6. Thirteen of 18 subjects were positive for EGF. The reaction for EGF receptor was positive in 20% of 12 patients with intestinal type tumors and in 67% of 7 patients with diffuse tumors. Reaction for EGF was positive in 80% of intestinal type tumors and 64% of diffuse tumors. Simultaneous positive reactions for both antigens was observed in 5 of 18 patients, all with diffuse type tumors. Signet ring cell tumors showed less positivity than less differentiated ones. Thus, the expression of EGF and EGF receptor was higher in our patients with advanced gastric cancer than reported elsewhere. PMID- 1305312 TI - [Etodolac versus piroxicam in the treatment of acute lumbago. Double-blind study]. AB - To evaluate the efficacy of the nonsteroidal anti-inflammatory drug etodolac, a comparative, double-blind study versus piroxicam was carried out. Two homogenous groups (in terms of age, sex, time since last crisis and duration of present episode) of patients suffering from acute lumbar pain were treated during one week with either etodolaco, 300 mg b.i.d. (n = 30) or piroxicam 20 mg/day plus placebo (n = 31). Diagnosis was confirmed by history, physical examination, and Rx studies. Several clinical parameters were assessed prior and after treatment. All 61 patients completed the study. Adverse drug reactions were evaluated in the final visit. No significant differences were established between groups in relation to efficacy. Compared to baseline, statistically significant relief of symptoms was achieved in both groups, for pain intensity (p < 0.005); sleep quality (p < 0.005); paravertebral muscles spasm (p < 0.005) and spinal range of motion (p < 0.005). Patients treated with etodolac exhibited significantly less adverse reactions than those on piroxicam (p < 0.025). PMID- 1305313 TI - [Convulsive electrotherapy in Parkinson disease. Presentation of a clinical case]. AB - Electroshock therapy was performed in a patient with Parkinson disease who had shown intolerance to treatment with levodopa. Evaluation at 1 and 6 months post therapy revealed mild and short lived antiparkinsonian effects. The theoretical basis for this therapy are discussed. PMID- 1305314 TI - [Fatal infectious endocarditis in a patient with annulo-aortic ectasia and predominant bicuspid valve aortic stenosis. Anatomoclinical case]. AB - A 25 year old female with bicuspid aortic valve and aortic stenosis developed infectious endocarditis due to beta hemolytic streptococcus. Specific antibiotic therapy was not successful, the patient developed multiple embolic episodes and platelet dysfunction that prevented surgery. The patient died 5 weeks after admission. Necropsy showed aortic annulo-ectasia, cystic medial necrosis and localized dissection of the proximal aorta. There were multiple aortic valve vegetations and evidence of inflammatory myocardial involvement, coronary embolization and myocardial infarction. Aortic annulo-ectasia should be investigated in patients with aortic valve endocarditis and early surgery would be advised to prevent aortic dissection. PMID- 1305315 TI - [Treatment of anorexia nervosa]. AB - Treatment of anorexia nervosa integrates psychiatric and medical aspects. Elements of analytically oriented (not true psychoanalysis) and behavioral forms of psychotherapy are utilized. Emphasis should be placed in the setting, patient therapist relation, and alliance with the family. Weight gain is the gauge and one of the goals of the therapy, having in mind that as it increases anxiety may be generated. From a behavioral point some restrictions are indicated. Antipsychotic (or neuroleptic) and antidepressant drugs should be used. Haloperidol is the drug of choice among antipsychotics while amitriptyline is usually preferred as antidepressant. General medical measures include adequate nutritional support, limitation of physical activity, eventual supplementation with iron, folic acid and vitamin B12. Estrogen therapy associated to progestins, calcium and vitamin D should be considered to prevent osteopenia. PMID- 1305316 TI - [Basis for changes in medical education]. AB - Medicine and medical education are going through a critical period due to a series of factors. Amongst them the explosion of knowledge and the progress in technology, and on the other hand the inefficiency of traditional medicine to cope with frequent and important health problems. We propose a medical education model based on a wider traditional model that incorporates social and psychological aspects of medicine emphasizing on prevention of disease and promotion of health. This model offers new methodological alternatives centered in the identification of problems, the acquisition of information and decision making, rather than in the storage of information. PMID- 1305317 TI - [Septicemia?, bacteremia?, sepsis?, septicopyemia?]. PMID- 1305318 TI - [Continuous arteriovenous hemodialysis using a cuprofan membrane]. PMID- 1305319 TI - [Workers exposed to styrene: application of a neuropsychological evaluation computer system]. AB - The purpose of this study was to adapt and apply a battery of neuropsychological tests administered by computer. The study comprised three phases: 1) An existing system (NES-2) was revised and adapted (mainly in its Spanish version, since the structure and time intervals were the same). 2) A pilot group of 18 subjects was administered the five selected tests. 3) A comparative study of 36 exposed workers with 40 unexposed controls was undertaken. It was concluded that computer administered tests are acceptable and economic. No significant differences were found between exposed. The possible reasons for the negative findings are discussed, as well as the types of future studies that need to be carried out. PMID- 1305320 TI - [Andres Bello and the origins of the University of Chile]. AB - During colonial times the Royal University of San Felipe was founded in 1738. The first plan for medical studies was outlined in 1779. During the Independence, the National Institute created in 1813 took over higher education. The first Course of Medicine was dictated there in 1833. The University of San Felipe was replaced by the University of Chile in 1842. Andres Bello, its first Rector, developed the constituting laws of the University. PMID- 1305321 TI - Influence of cloprostenol in the experimentally induced ulcer in rats. AB - We have tested the action of cloprostenol a relatively stable analogue of PGF2 alpha in experimentally induced gastric ulcer in rats by contention stress or indomethacin. Our results show that CIPG, administered at higher doses than those inducing an luteolytic effect, has a gastroprotective effect both in the contention stress-induced ulcer (2.30 + 0.26 in series III as compared to 3.80 +/ 0.73 in series III, p < 0.01) and in indomethacin-induced ulcer (2.69 +/- 0.38 in series V as compared to 3.61 +/- 0.34 in series IV, p < 0.01). PMID- 1305322 TI - An overview of oncogenesis. AB - The paper reviews the actual knowledge in the field of oncogenesis, according to the oncogene theory of cancer. The main actions of proto-oncogenes during cellular proliferation are outlined and oncogenes are classified to their specific roles. The relationships between proto-, viral-, and cellular oncogenes are analyzed and the several steps of the evolution of a p-onc towards a c-onc are described. Several examples of better known oncogenes are presented to illustrate the interrelations between the families of genes and their interactions during oncogenesis are evoked. As the implication of each c-onc in distinct neoplasia can be suspected according to the most frequent genomic alteration of each type of cancer, information about the chromosomal localization of oncogenes is comprised. The oncogenes' products, their weight and cellular position are also presented. The onco-suppressor genes, oncogenes' counterparts are also described, their localization being deduced from analysis of frequent breakpoints or mutation site/s in cancers. Finally, future perspectives of oncogene research are also outlined. PMID- 1305323 TI - [Polycystic kidney disease with autosomal dominant transmission]. AB - Autosomal dominant polycystic kidney disease affect adults starting the 5th decade of life. It is caused by at least two different gene defects, one gene being located on the short arm of chromosome 16. It's more frequent at women and clinically, near renal cysts, appear others systemic manifestations as hepatic cysts, intracranial aneurysms, cardiac valvular lesions or diverticula. The diagnosis is set up on urography and ultrasonography and the treatment attempt to slow down the evolution to renal failure and to prevent the complications as infections, obstructions and hypertension, that may aggravate the prognosis. Lately there are discussions about a preventive treatment consisting in genetic counseling. PMID- 1305324 TI - [The effect of prostaglandins and nonsteroidal anti-inflammatory agents on the immune system]. PMID- 1305325 TI - [A group of 4 students has initiated the establishment of a new section within the Society of Physicians and Naturalists]. PMID- 1305326 TI - Meigs' syndrome. A case report and review of literature. AB - A 31-year-old woman, with primary infertility associated with cervico-vaginal defect, presented with intermittent breathlessness often correlated by the patient with menses, cough and chest pain. The symptoms had lasted for 6 months, and were attributed to a pleurisy, which was confirmed at roentgenology and treated by frequent thoracentesis, evacuating in all over 15 liters of fluid. Several aetiologies were excluded, such as: viral, TB, L.E., neoplasia, liver disfunction. A gynecological ultrasonography finally diagnosed a solid extensive ovarian tumour. Right oophorectomy has completely stopped pleural effusion relapse. We consider this case representative for the importance of a serious consideration of Meigs' syndrome in any recurrent pleurisy. We also believe our case to support the hypothesis of a hormone implication in Meigs' syndrome cause, as the symptoms correlated with menses, and especially as the morphopathological diagnosis was ovarian fibroma with myxoid areas, which could be incriminated for the patient's primary infertility, but it was not properly investigated. PMID- 1305327 TI - [Beta-thalassemia major: a clinical case]. PMID- 1305329 TI - [The placebo phenomenon and effect--the pathway linking man with physical reality and man with mental reality]. PMID- 1305328 TI - [A possible structural model of the gastric barrier]. PMID- 1305330 TI - [Do you know how to present your personality?]. PMID- 1305331 TI - Effect of glyceryl trinitrate on proximal stomach musculature in normal volunteers. AB - The effect of GTN on stomach is unknown although there is evidence that nitric oxide, the active component of GTN have a mediator role in the upper gastrointestinal tract. By the use of a newly developed barostat technique it was investigated the effect of GTN on gastric fundal tone and contractions. METHOD: measurements were done 1 hour before an 1 hour after the administration of either 500 micrograms sublingual GTN and 5 mg buccal GTN or a placebo in 7 healthy individuals (14 experiments) by recording variations in the volume of air within an intragastric bag that was maintained at a constant pressure of 12 mmHg by the barostat. RESULTS: a significant increase in intrabag volume of 99.74 +/- 28.34 ml (mean +/- SEM) (p < 0.01) was recorded after GTN administration; a not significant (p > 0.01) increase in volume of 24.34 +/- 16.23 ml was after placebo. There was no significant difference between the frequency of contractions before and after drug or placebo administration. CONCLUSION: after systemic and constant administration of GTN a constant reduction in gastric fundal tone is produced with no change of fundal contractions. PMID- 1305332 TI - Effect of age on fattening and body condition of draught oxen fed teff straw (Eragrostis teff) based diets. AB - Twenty-four Ethiopian Highland Zebu (Bos indicus) oxen were allocated to 6 groups of 4 animals each on the basis of liveweight, age and body condition according to a completely randomised block design. The animals were group-fed an experimental diet consisting of (g/kg) 551 g concentrate and 449 g teff straw, at the rate of 2.5 kg per 100 kg of liveweight for 18 weeks. They were weighed and condition scored weekly. Feeding levels were adjusted weekly. The daily liveweight gain of each animal was estimated using regression analysis and changes in condition score evaluated. Age significantly affected the liveweight gains and body condition score changes of the oxen. There was a significant (P < 0.001) linear effect of age on average liveweight gain. The average daily gains were 0.62, 0.51 and 0.41 kg/day for animals aged 4 to 5, 7 to 8 and 10 to 11 years respectively. Age exhibited a significant (P < 0.05) quadratic effect on body condition changes. The results are discussed in terms of benefits from traction and fattening and farm system implications of fattening younger animals for reproduction and improved feeding. PMID- 1305333 TI - Liveweight estimation of cattle by scale and by tape, a method comparison study. AB - The repeatability of weight estimation of cattle by scale and by tape and the agreement of weight estimates obtained by the 2 methods were evaluated. The within-subject standard deviation of replicates was used as a measure of repeatability while the agreement of the 2 methods was evaluated by analysis of the differences in weight estimates. In young cattle, the measurement error of the tape was about twice that of the scale while in adult cattle it was more than 4 times as great. Although weight estimates by the 2 methods were highly correlated, considerable differences occurred in individual cattle. The same was true for estimates of weight gain. It does not appear advisable to use the tape in trials where weight is an independent variable whereas the use of the tape can be justified in experiments where weight is the dependent variable. PMID- 1305335 TI - Louse and mite infestation in domestic animals in northern Nigeria. AB - Records of domestic animals brought to the Veterinary Entomology Laboratory for diagnosis of suspected lice and mite infestation over a 10 year period were analysed. From a total of 794 suspected cases, 137 (17.3%) and 247 (31.1%) were positive for lice and mange mites respectively. The most common lice species recorded were Linognathus vituli (66.7%) on cattle, L. ovillus (83.3%) on sheep, Haematopinus suis (100%) on pigs and Menacanthus stramineus (54.5%) on poultry. Other lice species recorded included Haematopinus bovis and Solenopotes capillatus on cattle, Damalinia ovis on sheep, Linognathus stenopsis and Menacanthus stramineus on goats, Goniocotes sp. on a horse, Linognathus setosus and Menacanthus stramineus on dogs, Goniodes gigas, Lipeurus caponis, Menopon gallinae and Chelopistes meleagrides on poultry. The most common mite species were Demodex folliculorum on cattle (96.9%) and on dogs (80.8%), Sarcoptes scabiei on pigs (100%) and Notoedres cati (80.3%) on rabbits. Other mite species included Psoroptes communis, Cheyletiella parasitivorax, Ornithonyssus gallinae and Dermanyssus gallinae. PMID- 1305334 TI - Copper status of Najdi sheep in eastern Saudi Arabia under penned and grazing conditions. AB - Concentrations of serum copper were significantly lower in penned Najdi sheep (zero grazed) than in grazing sheep in eastern Saudi Arabia. Soil-plant-animal interrelationships studies suggest that this could be attributed to the low copper to molybdenum ratio in the forages (berseem and Rhodes grass) fed to the penned sheep as compared to pasture plants. This was in line with the status of these minerals in the soils. PMID- 1305336 TI - Prevalence of leptospiral antibodies in cattle in northern Jordan. PMID- 1305338 TI - Indigenous and crossbred cattle--a comparison of resistance to ticks and implications for their strategic control in Zimbabwe. AB - A comparison of the tick resistance of indigenous Mashona and crossbred Afrikander x Sussex oxen following natural tick infestation indicated that significantly more African blue ticks Boophilus decoloratus were found on the crossbred than the indigenous cattle (P < 0.05). The two groups of cattle were exposed to Babesia bigemina and Theileria taurotragi as indicated by high antibody titres on the indirect fluorescent antibody test, but no antibodies could be demonstrated to Anaplasma marginale and T. parva bovis despite the presence of their vectors. Rhipicephalus appendiculatus, Hyalomma truncatum and H. marginatum rufipes showed a seasonal distribution. The implications of the findings in terms of strategic tick control are discussed. PMID- 1305337 TI - Isolation of drug-resistant strains of Trypanosoma congolense from the lower Shabelle region of southern Somalia. AB - Drug resistance by pathogenic trypanosomes in Somali livestock has been suspected for some time but there have been few attempts to examine this problem in detail. Field isolations from two areas in the Lower Shabelle Region were obtained by injecting blood from trypanosome infected cattle into a recipient calf. Once the calf became parasitaemic it was treated with a standard dose of isometamidium chloride (Samorin, RMB) at 0.5 mg/kg. When a subsequent relapse infection developed, indicative of drug resistance, blood was taken and injected into groups of cattle and mice and these were treated with a range of doses of isometamidium chloride and diminazene aceturate (Berenil, Hoechst AC) to determine the degree of drug resistance. Both isolates showed remarkably high levels of drug resistance to both isometamidium chloride and diminazene aceturate, with minimum curative doses in cattle of > 2.0 mg/kg and 7.5 mg/kg for the two drugs respectively. Minimum curative doses in mice were approximately ten fold those in cattle. Fortunately there have been a very few reports from Africa of such high levels of resistance of Trypanosoma congolense to this normal "sanative pair" of drugs. The results indicate that drug resistance could be an important constraint on the use of trypanocidal drugs to control trypanosomosis in Somalia. PMID- 1305339 TI - Cattle production systems in the derived Savannah and southern Guinea Savannah regions of Oyo State, southern Nigeria. AB - A single visit questionnaire survey was undertaken on 50 cattle owners in Oyo State, south-western Nigeria. Data were collected on grazing patterns, calving dates, calf mortalities and attitudes to the N'Dama breed and its crosses with Bunaji cattle. All cattle herds had similar grazing patterns, using natural pasture from April to November, crop residues in December, pasture regrowth after burning plus crop residues in January and regrowth and browse in February and March. The conception pattern was unimodal, reaching a peak in July after the new grass growth from the first rains. Calf mortalities were highest between 2 to 4 months of age during the early rainy season, but were significantly lower in mixed N'Dama/Bunaji herds than in the Bunaji herds. Most cattle owners were interested in purchasing N'Dama breeding stock, believing them to be more productive. This is a move away from the traditional pastoralist practice of keeping only Bos indicus breeds. PMID- 1305340 TI - An outbreak of haemorrhagic septicaemia (septicaemic pasteurellosis) in cattle in Zimbabwe. AB - An outbreak of haemorrhagic septicaemia caused by Pasteurella multocida in beef cattle in Zimbabwe grazing effluent-irrigated pastures, is described. The outbreak occurred during the wet summer months and predisposing stress factors included excessive rainfall and unusual cold weather during the preceding month. History, clinical features and post-mortem findings were consistent with reports of the disease from other countries, except that meningitis was also a constant feature. Morbidity approached 77% and mortality 5 per cent. Prophylactic treatment and vaccination with a killed bacterin together with a return of warmer and drier weather were probably important in halting the outbreak. PMID- 1305341 TI - Livestock development policy in The Gambia: a reassessment. AB - This paper examines the historical development of policy in The Gambia through an analysis of 3 recurring themes: the motivation for keeping livestock, growth of the cattle population and the resulting feed deficit, and the need to develop a mixed farming system. The paper argues that there are major discrepancies between the common understanding which emerges from these themes and the realities of livestock ownership and production. It is suggested that it is because of these discrepancies, that livestock policies and programmes, other than mass disease control, have seldom had their desired impacts. PMID- 1305342 TI - Duration of carrier state following vaccination with live Anaplasma centrale. PMID- 1305343 TI - Isolation and characterisation of Newcastle disease virus strain in a feral dove (Stigmatopelia senegalensis) in Nigeria. AB - An isolate of Newcastle disease virus (NDV) was obtained from a feral dove, (Stigmatopelia senegalensis). The isolate was shown to have a mean-death-time of 96 h and an intracerebral pathogenicity index of 0.10. It was immunogenic but not pathogenic for 6-week old chicks on experimental infection. Based on these observations the isolate was classified as a lentogenic strain. The role of such isolates of NDV from wild birds on the Nigerian poultry industry is discussed. PMID- 1305344 TI - Seasonal influences on gonadal and extragonadal sperm reserves in Small East African zebu (Bos indicus) bulls in Ethiopia. AB - Body weight and scrotal circumference (SC) data were taken ante mortem and genitalia collected after slaughter from Small East African zebu (SEAZ) bulls slaughtered during the wet (n = 46) and the dry (n = 53) seasons. Bulls slaughtered during the wet season were significantly heavier (47 kg) and had significantly larger SC measurements (3.3 cm) than those slaughtered during the dry season. Mean (+/- s.e.m.) paired testes weights were 233.7 +/- 13.8 and 292.8 +/- 11.3 g and epididymal weights 26.8 +/- 0.9 and 35.9 +/- 1.1 g in bulls slaughtered during the dry and wet seasons, respectively. Daily sperm production rates and epididymal sperm reserves were 2.2 +/- 0.1 x 10(9) and 3.0 +/- 0.1 x 10(9); and 16.1 +/- 0.3 x 10(9) and 17.6 +/- 0.4 x 10(9) in bulls slaughtered during the dry and wet seasons, respectively. These differences were significant. It was concluded that season affected reproductive capacity of zebu bulls probably due to variations in the quality and quantity of nutrition. However, the confounding effects of ambient temperature and nutrition on reproductive capacity of zebu bulls in tropical regions need further examinations. PMID- 1305345 TI - Season and location effects on serum and liver mineral concentrations of Senepol cattle on St Croix, Virgin Islands. AB - Serum and liver concentrations of selected macro- and trace minerals were determined in Senepol cattle at 8 sites (4 each in a high and low rainfall region) during the dry and wet season on St Croix. At each site an average of 15 mature, lactating cows, grazing native grass/legume pastures without supplementation were blood sampled each season. Liver samples were collected (n = 51) at slaughter from mature animals originating from the same sites. A preliminary analysis indicated no differences in serum mineral concentrations between mature lactating cows and growing heifers. There were differences between sites for serum magnesium (Mg) (P < 0.001), copper (Cu) (P < 0.05) selenium (Se) (P < 0.001) and zinc (Zn) (P < 0.01) in the dry season, and for Cu (P < 0.01), iron (Fe) (P < 0.001) and Zn (P < 0.01) in the wet season. Higher (P < 0.001) serum concentrations of Mg, Cu, Fe and Zn were observed in the dry season, while Se was higher (P < 0.01) in the wet season. Liver concentrations of Cu and Fe were lower (P < 0.01) and liver molybdenum (Mo) (P < 0.001) and Se (P < 0.05) higher during the dry season. The seasonal differences in serum Cu, Se and Zn concentrations have not been observed in other studies in the Central American region. More than 50% of serum samples were deficient in phosphorus (P) regardless of season, and in Cu and Zn during the wet season. Mineral supplementation should be considered. PMID- 1305346 TI - Genetic and environmental variation in reproductive and lactational performance of Jersey cattle in the coastal lowland semi-humid tropics. AB - Reproductive and lactational performances, including length of productive life, were evaluated from records for 1960 to 1988 for a Jersey herd in coastal lowland semi-humid Kenya. The herd grazed natural pastures and until the mid 1970s received supplementary feeding. Mean performance included 31 months age at first calving, lactation milk yield (MY) of 1,788 kg in 3.3 lactations and a calving interval (CI) of 408 days. Mean milk yields declined from over 2,200 kg in the 1960s to about 1,500 kg in the 1980s with concomitant changes in calving interval, length of productive life and infertility. While annual genetic components of change in MY and CI were not significantly different from zero, the environmental components were large and significant (P < 0.01) showing that the declines in performance probably resulted from decreased feed availability and less efficient disease control. Estimates of genetic parameters were consistent with those in the literature. With good management purebred Jersey cows in coastal lowland semi-humid Kenya were productive, but animal and herd productivity were highly dependent on management level which had a major effect on both milk yield and reproductive wastage. PMID- 1305347 TI - Plasma progesterone concentrations during pregnancy and pseudopregnancy and onset of ovarian activity post partum in indigenous goats in Zimbabwe. AB - Eight pregnant does were housed individually and fed a hay and concentrate diet throughout pregnancy and lactation. The mean gestation period was 146.7 +/- 3.0 days, with a twinning rate of 75 per cent. Mean body condition scores improved from 2.4 +/- 0.2 to 2.8 +/- 0.2 over the first 80 days of gestation and were maintained at 2.8 until 45 days before kidding. From then until kidding, mean scores fell to 2.2 +/- 0.2. Plasma progesterone concentrations during pregnancy rose significantly from 3.91 +/- 0.51 ng/ml on day 40 to 5.96 +/- 0.51 ng/ml on day 60 (P < 0.05) and remained high until 5 days before kidding. Three pseudopregnant does had similar progesterone profiles to pregnant does over the first 80 days, but the rise around day 35 to 40 was not significant and progesterone concentrations returned gradually to basal levels after day 100. The same 8 does, together with an additional 4 does which had been brought inside 60 to 70 days before kidding, were used to study onset of ovarian activity post partum. The twinning percentage was 83 per cent. Mean body condition score at parturition was 2.2 +/- 0.1. By day 35 post partum, mean condition scores had fallen to 1.9 +/- 0.1, and mean weights from 36.9 +/- 1.9 kg at kidding to 32.1 +/- 2.0 kg. Ovarian cyclicity was resumed just before mean scores and weights started to improve. The mean interval from kidding to onset of oestrous cycles was 97.3 +/- 9.5 days. This coincided with mean time to weaning which was 99.5 +/ 5.5 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305348 TI - Pelagic whole fish (Rastriobola argenteus) as a protein source for pigs. AB - Two trials were carried out to investigate the potential of small pelagic fish (Rastriobola argenteus) locally referred to as omena, as a protein supplement for pigs. In trial one, 12 growing pigs were fed on diets containing either soyabean meal or omena for 30 days. The average daily gains, daily feed intakes and feed to gain ratios were 814 g, 2.01 kg, 2.47 and 831 g, 1.98 kg, 2.38 for the soyabean meal and omena diets respectively. All these performance indicators were similar between the 2 dietary treatments. In the digestibility study involving weanling rats, the digestibility of dry matter was not affected by diet but that of protein and ash were different between the 2 diets (P < 0.05). The digestibilities of dry matter, crude protein and ash were 75.8, 66.0, 56.9 and 77.6, 71.3, 39.2 for soyabean meal and omena diets respectively. Rastriobola argenteus (omena) is a potential protein supplement for pigs. PMID- 1305349 TI - Effects on feedlot performance and carcass quality of substituting date syrup for barley in rations for lambs. PMID- 1305350 TI - [Epidemiology of alcohol and drug abuse in Paraguay]. AB - The results of a prevalence study on use- and abuse- of psychoactive substances, among a population aged 12 to 45 in Paraguay are presented. Presence of the depressive syndrome as well as attitudes and beliefs related to the use of psychoactive substances were also investigated. A bilingual questionnaire was drafted--i.e. a Spanish version and a Guarani version due to the Paraguayans' bilingual characteristic--that yielded acceptable validity and reliability levels. A stratified random sample was applied, with a total of 2,504 questionnaires filled out. Weighted data are shown here as studied by sex, age group, socio-economic level, and presence of the depressive syndrome. Substance/alcohol use patterns were found out to be widely tolerant about abusing legal substances such as alcohol, tobacco, and psychotropic drugs. As regards illicit substances use, inhalants head the list followed by marijuana at a close range. PMID- 1305351 TI - [Primary prevention in mental health programs. Possible or impossible? Now or later?]. AB - The point in discussion is: Does any possibility exist of having primary prevention actions included in mental health plans and programs of the countries pertaining to the Latin-American and Caribbean region? On the one hand, such actions are becoming more and more necessary if the higher mental health demands are taken into account--which exceed the offer of services at a secondary preventive level. On the other hand, recent literature has been accumulating scientific evidence bringing rational basis for interventions at a primary preventive level. Mental health workers--if adequately trained--may find a fruitful field for action in assistance and research as well. PMID- 1305352 TI - [Creative moments during analytical processes]. AB - Examples from his clinical work are used by the author to illustrate creative instances during analysis. First, there appear a dis-idealization and a threat of chaos, followed by mourning, reparation and sublimation. The creative function originates in a patient's attempt to objectify his or her ego in different ways- which involves a phantasy of being re-born in order to love someone and be loved in turn. It represents a triumph of life over death, of health over madness. In other words, the creative function means putting psychic chaos into order with pre-existing elements by means of original, new, better-integrated changes. PMID- 1305353 TI - [Changes in psychiatric care. Reform or revolution? The experience of the Swedish model]. AB - Reforms to psychiatric practice in Sweden are discussed, expecting that the Scandinavian experience be of assistance as regards changes that are being implemented for a re-structuration of psychiatric care in Latin America. The following points are enhanced: (a) epidemiological studies as an important basis for planning and action in mental health; (b) a progressive closing of mental hospitals while, at the same time, more institutionalization capacities are being created at general health services, and (c) organizing non-hospital care by sectors with community mental health teams being in charge of. As far as negative aspects are concerned, a tendency towards a "psychologization" so to speak of social issues, and a certain lack of attention of patients with severer disorders are pointed out. PMID- 1305354 TI - [Functional dysphonia: relation with personality and ICD-10 criteria]. AB - The International Classification of Diseases, 10th. revision (ICD-10) in the category F45 defines the somatoform disorder as a mental disease characterized by the reiterative presentation of somatic symptoms in absence of an organic disease, or the somatic pathology being insufficient to explain the intensity of the symptoms as well as the discomfort and preoccupation of the patient. Fifteen female teachers with functional dysphonia were studied by means of a semistructured interview and psychometric evaluations. Considering dysphonia as the principal symptom, the most frequent diagnosis, in accordance with ICD-10 was "Other somatoform disorder" (F-45.8)(9/15). Five patients were diagnosed as motor dissociative disorder (F-44.4). All the patients had some abnormality of personality (5 with personality disorder and 10 with exacerbation of personality traits). The criteria of ICD-10 to classify the functional dysphonia as Somatoform disorder are discussed. It is suggested that certain personality traits are facilitators for somatization. PMID- 1305355 TI - [Interdisciplinary ambulatory care in patients with chronic mental disease]. AB - The experience of an ambulatory treatment for mental chronic outpatients is presented. A trans-disciplinary group (including a psychiatrist, an occupational therapist, a social worker, a nurse, and a psychologist) worked during a 3-year period. Five specific clinics were created: Organic Mental Syndrome, Schizophrenia, Mood Disorders, Neurosis, and Psychoactive Substance Users. Results of the treatment are presented, showing the benefits such a clinical envisioning meant not only for the patients involved but also for their family, the hospital management, and the members of the therapeutic group as well. PMID- 1305356 TI - [Evaluating the efficacy of psychotherapy: follow-ups]. AB - The results of psychotherapeutic treatments administered at a private institution of the city of Buenos Aires--over a 200-case total--by means of a telephone calls follow-up procedure are discussed. A comparison is thus possible between the results achieved by the above mentioned institution's working team, and results as described in literature. At the same time, an important subgroup has been determined: Namely, patients who feel better after an only admission interview--a fact likely to make you think over people's mental resources. PMID- 1305357 TI - [Stress of teachers and students' violence]. AB - A training program for secondary school teachers, by the name of Stress inoculation, is presented. It is aimed at coping with conflictive situations likely to arise in a classroom. Adapted from D. Menchembaum's model, this program has been developed, and assessed at three secondary schools of the city of Buenos Aires: It is the author's contention that it lives up to her expectations. Teachers are trained to develop resources enabling them to: (a) recognize alarm signals arising in their relationships with students (i.e., signals advising that such relationships are in jeopardy), (b) cut sequences leading initial situations to burst out in violent behavior, and (c) incorporate coping alternatives when facing violent situations so that both teaching, and teacher-students relationship are preserved--as well as teacher's and students' mental health. PMID- 1305358 TI - [Psychopathology and psychosocial functioning of adults with epilepsy. Preliminary evaluation]. AB - To examine the relationship between psychosocial functioning and psychopathology in epilepsy, a total 37-outpatient sample was assessed by means of both the Washington Psychosocial Seizure Inventory (WPSI) and the Minnesota Multiphasic Personality Inventory (MMPI). Patients came from an epilepsy program of the Hospital psiquiatrico, Chile. Disorders in several areas pertaining to psychosocial functioning and psychopathology were observed: Their distribution was quite similar to disorders previously reported when using both instruments. The WPSI scales showed a positive correlation with the MMPI's--a relevant correlation as far as the Overall Psychosocial Functioning, and Emotional adjustment sub-scales are concerned. The relationship between psychopathology and psychosocial functioning in epilepsy is discussed as well as the usefulness of the WPSI as a screening-test for the psychosocial assessment of epileptic subjects. PMID- 1305359 TI - [Vicenzo Chiarugi and the reform of asylums]. PMID- 1305360 TI - [Is it possible to build up an algorithm of the human soul?]. AB - The possibility of constructing a computer programmable algorithm able to generate behaviors indistinguishable from human behaviors is envisioned. First, a concept of algorithm is offered, this proposal is discussed, and, lastly, limitations to such a project are considered. PMID- 1305362 TI - [Gender role and anorexia nervosa]. AB - The gender role is defined; its physiognomy, adopted by women since the occurrence of the Industrial Revolution, and the intricate status that characterizes the present feminine role are described. Finally, a psychosocial approach of anorexia nervosa is made. This disorder is considered as a paradigm of the present ambiguity of the femininity concept likely to become a transactional phenomenon between sexual identities. PMID- 1305361 TI - [Obesity and feeding behavior: diagnostic and psychometric aspects]. AB - Obesity is regarded in its triple connotation of symptom, risk factor and homeostatic organization, stressing the inadequacy of traditional formulations about psychological causation. Psychological factors most frequently associated to obesity are excessive intake, complications of dieting and alterations of body image. The predictive role of psychophysiological dimensions of Restraint, Disinhibition and Hunger is discussed on the basis of empirical information. ICD 10 formulations are considered a positive advance in the taxonomy of syndromes with alterations of body weight. PMID- 1305363 TI - [Insufficient sex education in medicine]. AB - The present paper--actually a synthesis of the author's thesis for M.D. degree- aims at pointing out the need there is for an MD-oriented education in normal and pathological sexuality to be implemented. A 228-medical student/175-physician sample was administered the well-known SKAT test altogether with a questionnaire dealing with sexual personal experience, contraception procedures, and self evaluation on knowledge, training, and personal attitude toward sex-related matters. Results showed mistakes and misinterpretations in the area of knowledge of both groups: Personal experience appears to be a physician's sole guideline. Doctors' reluctance to approaching sexual matters when writing clinical records was also observed, an aspect confirming physicians' limitations--in connection not only with knowledge per se but also with inhibitions shared by both a professional and his or her patient. Thus, the convenience of implementing sexual education as another subject in curriculum is suggested. PMID- 1305364 TI - [Psychosocial intervention in hospitalization due to alcoholism]. AB - This paper presents a descriptive-type research on the findings of a 1-year follow-up experiment on a 72-inpatient at the Instituto sobre Alcoholismo y Farmacodependencia of the city of San Jose, Costa Rica. Information wa obtained from a 59-question instrument aimed at exploring: Sociodemographic aspects, alcohol ingestion-abstention patterns; interpersonal, family and labor relationships, autodiagnosis, and evaluation of the treatment program. During the 3-week inpatient treatment, a psychosocial treatment was administered to all subjects. Owing to the substantial changes patients evidenced in the above mentioned areas, findings suggest that the objectives were fulfilled satisfactorily enough. PMID- 1305365 TI - [Stereotype, self-stereotype and metaperception of men and women]. AB - Male and female self-stereotype, and metaperception were studied in a 613 University student sample (291 men, 322 women). Seventy-nine bipolar items from the Factorial Scales of Self-concept were used as a measure. Factor analyses of items were independently calculated for their application to both men and women. The principal findings were as follows: 1) Male stereotype basically includes instrumental characteristics while female stereotype includes expressive as well as instrumental attributes; 2) Male and female self-stereotypes are in accordance with their respective stereotypes; 3) Men as well as women have a fairly accurate idea of how they are perceived by the opposite sex. PMID- 1305366 TI - [Colored matrices test (special scale): how to evaluate and interpret it in our milieu]. AB - Raven's "Colored Matrixes" (Special scale) were specially adapted for 5- to 11 years-old children by their author. The present paper analyzes: 1) The importance of taking into account wrong responses to the matrixes since they are likely to occur at a higher (5/6) probability level than correct responses (Burnbaum, 1968; Bock, 1972); 2) The proposal of considering the Colored Matrixes as a test with cultural reduced influences. The findings of a research carried out with 790 preschool- and schoolchildren (ranging 4- to 11.5-years-old) in Argentina are presented: Total scoring, and series scoring are shown. By means of a multiple variance analysis it has been found out that both age and series, as well as the interaction between both have a statistically significant influences on score variations. Besides, new evaluation guidelines are presented. PMID- 1305367 TI - [Use of the perceptive stimulative model (PSM, Romano, 1979) as an individual and/or group diagnostic test]. AB - MEP (Spanish acronym for Perceptive-stimulative Model) is a visual test whose nimble and simple administration is apt for both individual and group studies. As a diagnosis complementary instrument, its design has been arranged so that the perceptive material (i.e. geometric outlines) offers information on the degree of integration of ego functions, an analysis of which allows perspectives applicable to diagnosis, prognosis, and therapeutical orientation. At the same time, such analysis enables hypotheses related to the interaction potential of patients involved to be advanced. PMID- 1305369 TI - [Science, technique, ethics. The psychiatric profession in Latin America]. PMID- 1305368 TI - [The professor of psychiatry Dr Oscar Fontecilla]. PMID- 1305370 TI - [The anatomy of the liver]. PMID- 1305371 TI - Diagnostic management and classification in hepatic trauma. PMID- 1305373 TI - Prognostic factors in the management of blunt hepatic injury. PMID- 1305372 TI - [The surgical therapy of liver trauma]. AB - The different therapeutic patterns of liver trauma are presented; they should be chosen on the basis of both clinical assessment, particularly looking for hemodynamic impairment and associated bowel lesions, and CT scan data. Surgical abstention should be considered for a great number of blunt liver trauma; open or severe blunt trauma should be preferably treated by elective hemostasis and biliostasis, with only rare use of hepatic resection "a la demande", on partially sectioned or devitalized tissues. Cavo-suprahepatic wounds remain the most important technical problem and continue to worse the prognosis in liver trauma. PMID- 1305374 TI - Blunt and penetrating liver trauma: surgical strategies. AB - From our own experience with 104 patients with liver trauma treated by laparotomy we confirmed the present trends in treating blunt liver trauma, i.e. conservative therapy of minor lesions under closed observation with imaging procedures (US and CT-scan); minor local measures in superficial liver injuries when laparotomy is performed for other reasons; generous use of the Pringle maneuver in primary hemostasis; temporary or final treatment by perihepatic packing in all parenchymal fractures with predominant venous bleeding; direct suture or ligation of arterial bleeding; liver resection only for the debridement of destroyed tissue. With primary packing the patient can be transferred to an experienced center. The overall mortality is more dependent on combined lesions from polytrauma. The early and efficient hemostasis of liver trauma may, however, stabilize the border-line patient and give him a better chance. This is underlined by the experience, that isolated liver injuries have a much better prognosis except central lesions of the retrohepatic vena cava and large central hepatic veins. PMID- 1305375 TI - [Hemobilia as a consequence of liver contusions]. PMID- 1305376 TI - [The secondary treatment of liver trauma]. PMID- 1305377 TI - Clinical evaluation of hepatic lesions: guidelines for diagnostic protocols and injury severity scores. AB - The standardisation of diagnostic procedures according to an adequate sequence is a mandatory in determining the therapeutic strategy in liver traumas. In a series of 26 consecutive cases of trauma of the liver, 3 of them penetrating, we adopted a diagnostic algorithm based on the extensive use of sonography and "Injury Severity Scores" in addition to the standard clinical procedures. The treatment of the lesions was surgical in 21 cases (81%) and conservative in 5 (19%); post operative mortality was 14% and overall mortality 11.5%. None of the cases treated by conservative approach had to be submitted to surgery during the follow up period. Sonography, carried out by surgical staff within 30' from observation and at definitive intervals, allowed a correct surgical approach in all cases; a similar sensitivity was obtained by sonography also in the cases treated conservatively and submitted to C.T. evaluation. The absolute correlation between Revised Trauma Score, Injury Severity Scale, classes of severity of the lesions and subsequent surgical survey suggest that this scoring system could be adopted in the first triage of traumatic lesions of the liver. Sonography could be preferred to diagnostic peritoneal lavage in the screening of cases with circulatory instability; furthermore, it could be a valid alternative to C.T. in hemodynamically stable patients. PMID- 1305378 TI - [Nutritional treatment in the therapeutic strategy in benign esophageal stenosis]. AB - Oesophageal strictures prevent a normal alimentation, and in chronic and more prolonged cases are the cause of severe denutrition. Many organs then undergo changes reflected on ultrastructural morphology, that in most severe and lasting cases can demonstrate irreversible. The functional aspect of such changes correspond to a hindered performance of the damaged organs with possible sudden cardiovascular accidents, which are particularly meaningful in the surgical steps of reconstruction, that is heavy for the patient not only in the perioperative period but also during the recovery when higher are the caloric energetic requirements. For the positive outcome of the surgical therapy of these strictures it is therefore necessary to preventively restore an acceptable nutritional status of the patient by the use of one or more of the nowadays available techniques of artificial nutrition. A particular topic of the need of a efficacious nutritional treatment can be pointed in the cases of oesophageal caustic burns, where the caloric requirements is high since the beginning to meet the catabolic effects of the traumatic condition, while malnutrition represents one of the negative factors in prolonging connettival and fibroblastic proliferation, cause of most severe strictures and recurrences. After a general survey of the whole problem, the characteristics of the various artificial nutrition techniques are discussed, with the identification of an optimal scheme of global and nutritional treatment in oesophageal caustic burns. PMID- 1305379 TI - [The risk factors for liver and kidney complications in general surgery: the results of a prospective multicenter study]. AB - A method for preoperative assessment of surgical risk, in function of several risk factors, was developed using the multiple logistic function, as a model of multivariate statistical analysis. This model has the advantage to express the two considered outcomes (perioperative complications and death) in numerical terms of probability. The data were obtained from 1182 consecutive patients, 14 yrs or more, admitted to six centres in various regions of Italy. Stepwise logistic regression model was applied to a set of preoperative and operative factors, three of which were found to significantly correlate with postoperative hepatic failure: compromission hepatic function time of surgical operation > 120' and nutritional status. The factors significantly correlate with postoperative renal failure were: compromission renal function, bacterial contamination during surgery, time of surgical operation > 120'. PMID- 1305380 TI - [Latent pathology of the thyroid: an epidemiological and statistical study of thyroids sampled during 507 consecutive autopsies]. AB - In order to highlight the occult pathology of the thyroid in the aged, the authors examined all the glands withdrawn from 507 consecutive autopsies on subjects of 67.10 years of median age. In 10 tables there are weight and measurements of the thyroids, macro and microscopic details and pathologic appearances. Adenomas were found in 17.1% of cases and histologically besides the known cases referred also to the Hurtle cells type, 4 clear cells adenomas and 5 adenolipomas were found. In 27.42% the subjects were affected or were dead for a malignant extrathyroidal neoplasm, and in 26% of these there was a metastasis in the thyroid. Never a primitive thyroid carcinoma, macroscopically and clinically evident, but in 53 thyroid glands, 54 occult carcinomas (OC) were found, particularly 37 papillary and 17 medullary. IN 57% of 165 histologically treated thyroids, to evidence C-cells, hyperplasia of these cells was found associated with various pathologic conditions, more in aged subjects. In 147 glands were found 170 nodules of various number of cells, at times positive for calcitonin. These solid cellular nodes (SCN) were evaluated as nodular C-cells hyperplasia. Besides isolated cases of acute thyroiditis (also the mycotic type), of tubercular thyroiditis and Hashimoto's, in 12% of the glands a lymphocytic chronic thyroiditis was found, frequently with Hurtle cells. Others observations were: basophilic thickening of colloid also with calcium oxalate crystals, lipoid degeneration of follicular cells and fat interfollicular and interlobular infiltration, thyroid amyloidosis, inner and media elastic calcification of thyroid arteries, presence of cysts with squamous cells coating, parathyroid glands and cartilage intrathyroidal plaques. PMID- 1305381 TI - [Conservative meso-pancreatectomy for cystic papillary tumor: apropos a case report]. AB - A case of papillary-cystic neoplasm of the pancreas is reported in a 22-year-old woman. The only symptom was a palpable pulsating mass in her upper left abdomen. A conservative surgical treatment was adopted, consisting of pancreatic body resection (meso-pancreatectomy) and pancreaticojejunostomy to distal pancreatic stump. These neoplasms are quite uncommon, and can be difficult to differentiate from other cystic lesions of the pancreas. Surgical excision is curative in these tumors and is the treatment of choice due to its low morbidity and good long-term survival. PMID- 1305382 TI - [Perforations of the colon]. AB - Perforations of the colon are a difficult problem for any surgeon, due the emergency they represent and the multiple clinical and pathological findings. Personal cases are revised and the opportunity of a case-by-case evaluation and of an eclectic surgical choice are stressed. PMID- 1305383 TI - [Extensive lymphadenectomy in the therapy of cancer of the left colon and rectum: an analysis of the anatomicopathological data]. AB - In the last 12 years in our surgical service, radical resection was performed in 142 patients with cancer of left colon and in 145 patients with rectal cancer. Extended lymphadenectomy was always realized: preaortocaval lymphadenectomy in colonic cancer; preartocaval and pelvic lymphadenectomy in rectal cancer. The incidence of C stage was 40.14% in cancer of left colon and 40.68% in rectal cancer. Neoplastic diffusion in preaortocaval lymph nodes was only in a patient with colonic cancer, never in patients with rectal cancer. The incidence of neoplastic diffusion in pelvic nodes was 3.12% (0 in superior rectum; 6.25% in medium rectum; 2.4% in inferior rectum). In 1 of 90 patients with tumour of medium or inferior rectum, we relieved tumoural involvement of pelvic nodes without neoplastic diffusion in regional nodes. These anatomo-pathological data subline: a) the low incidence of neoplastic diffusion in preaortocaval nodes in cancer of left colon and rectum; b) the importance of pelvic lymphadenectomy in cancer of medium and inferior rectum. PMID- 1305384 TI - [Malignant peritoneal mesothelioma: apropos a new case]. AB - Prognosis for patients with malignant peritoneal mesothelioma is very poor, and most patients are beyond cure by the time the diagnosis has been made. The pathogenesis of this uncommon neoplasm seems to be related to asbestos and radiation exposure. The authors report a case of diffuse peritoneal mesothelioma in a 33-year-old man. Since the patient complained of aspecific symptoms and both biochemical and "imaging" studies did not provide useful informations for a definitive diagnosis, an exploratory laparotomy was performed. Intraoperative histological findings demonstrated the presence of a malignant peritoneal mesothelioma which had spread all over the omentum; considering the inoperability assessment of this case, the operation was completed and the patient was dismissed with an adjuvant chemo-therapy. Five weeks later the patient died. PMID- 1305385 TI - [In memoriam Raffaele Paolucci of Valmaggiore]. PMID- 1305386 TI - [The lost world of Raffaele Paolucci]. PMID- 1305387 TI - [A re-evocation of Raffaele Paolucci]. PMID- 1305388 TI - Transcultural nursing considerations of child abuse/maltreatment in American Samoa and the Federated States of Micronesia. AB - A conceptual analysis focuses on defining child maltreatment from the perspective of two Island nations in the Pacific Basin, American Samoa and the Federated States of Micronesia. Based on a review of the literature on child maltreatment laws and cultural factors in each region, a range definition is proposed. The range definition is comprised of defining features and borderline features for child maltreatment as it exists across these cultures in the Pacific Basin. Defining features were derived from evaluation of child abuse and neglect laws in each specified population. Borderline features were derived from cultural factors in American Samoa and the Federated States of Micronesia. While these Island nations already have child abuse and neglect laws, they are adapted from the United States. The degree at which unreasonable harm becomes abuse is culturally dictated, hence, these territories of the Pacific Basin are seeking culturally specific terminology when defining child maltreatment. The findings of this analysis indicate the significance of transcultural knowledge in nursing practice and the legal accountability nurses hold on the issue of child maltreatment. PMID- 1305389 TI - [Allergic conjunctivitis]. AB - The eye reacts to foreign substances through a variety of specific and non specific defense mechanisms. Constantly exposed to a great variety of microorganisms, the eye is capable of protecting itself without altering its own structure and function. Its resistance relies upon anatomic and physiological properties of its external components (eyelids, tears, conjunctiva and cornea). Most of the times, the conjunctiva becomes affected, resulting in a clinical picture of conjunctivitis where allergy predominates, expressed as allergic rhinoconjunctivitis, allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis and flictenular conjunctivitis. The physiopathology is considered to be of type I reaction (IgE mediated). Frequent complains often associated with other allergic diseases are: pruritus, tearing, photofobia and ocular redness. The diagnosis of allergic conjunctivitis in done by means of a throughout clinical history, conjunctival citology and evaluation of specific IgE with immediate skin tests. Treatment is symptomatic (antihistamines, antibiotics and/or topic steroids), but prevention (environmental control and sodium cromoglycate) and specific immunotherapy must be considered. PMID- 1305390 TI - [Treatment of congenital facial paralysis with crossed innervation of facial nerve and electric field stimulation]. AB - Congenital facial palsy is a devastating deformity. At present time there are no reports of the early treatment of this disorder. The treatment may be to supply contralateral auto reinnervation to the affected muscles through a sural-facial nerve graft enhanced by electric field stimulation. The purpose of this paper is to report 5 cases of congenital facial palsy treated by a crossed sural-facial nerve graft, enhanced by electric field stimulation. One year after surgery, clinical and electrodiagnostic examinations indicate appropriate reinnervation activity in all the patients. PMID- 1305391 TI - [Neurological development disorders in very low birth weight newborns]. AB - Thirty very low birth weight newborns (less than 1,500 g) were evaluated at term from the neurological point of view, and were followed-up during the first 2 years of life by a multidisciplinary team, in order to detect long term sequelaes. There were 3 patients with major neurological disorders, and one third presented minor alterations. Neurological evaluation at term was a good sequelae predictor. No significative differences were found in perinatal variables: birthweight, gestational age, Apgar's score, ventilotherapy and with presence of intraventricular hemorrhage when normal outcome prematures were compared with those with neurological disorders. Blindness or deafness were not detected. It's important to continue the follow-up study up to the school age. PMID- 1305392 TI - [Indomethacin in the prevention of subependymal-intraventricular hemorrhage in preterm newborns with conventional mechanical ventilation]. AB - The results of a double blind study to evaluate the efficiency of prophylactic endovenous indomethacin versus placebo for prevention of intraventricular hemorrhage (IVH) in newborn infants between 28 to 36 weeks of age who were intubated at the delivery room and required mechanical ventilation in NICU are presented. Fourty six patients required mechanical ventilation, but 14 neonates had IVH evaluated by ultrasound when were admitted to the Unit. At least 32 infants were studied, 16 for each group. There were no differences between the groups in weight, gestational age, sex and delivery way. The mobility was the same in relation to hialine membrane disease, sepsis, pneumonie and pneumotorax. The placebo group had more frequency of PDA and mortality (P < 0.5). There were no differences in mean airway pressure and arterial gases, also in glucose, platelets and urinary volume. The indomethacin group had mayor urinary density and FeNa but the results were always in normal ranges. The IVH was the same in both groups. We concluded that the indomethacin at the levels used did not produced alterations, and if the IVH is not prevented, were observed lesser severity of the same and the frequency of PDA and mortality are lesser. But still is necessary more number of cases for best conclusions. PMID- 1305393 TI - [Multisystemic impact in the full-term newborn with perinatal asphyxia]. AB - We studied 30 full-term newborn infants, admitted to the newborn intensive care unit of "Manuel Gea Gonzalez" General Hospital between January 1, 1989 and December 31, 1990. All infants had 5-minute Apgar score of 5 or less. The disturbances related to: brain, heart, liver, bowel, coagulation system, calcium and glucose homeostasis were investigate in all cases. Of the 30 infants, 29 (97%) had developed 1 to 7 abnormalities in the systems studied. Most of them had from 2 to 5 abnormalities (77%). The commonest disturbance was brain involvement in 22 cases (73%); metabolic and coagulation changes had also been observed, while heart disturbances were less common. There was no significant difference between the intensity and number of systemic abnormalities observed in these infants and the alterations seen during pregnancy, labor, delivery, administration of anesthesia and Apgar score. These observations suggest a striking relationship between asphyxia in the newborn infant and the development of systemic disturbances. PMID- 1305394 TI - [The VATER association]. AB - The clinical, radiologic, and anatomic features of 53 patients with VATER association were reviewed. The vertebral, anorrectal, tracheoesophageal, radial, and renal congenital defects included in the association are similar to those described by other authors. In this report genital anomalies are very frequent and should be included as a diagnostic criteria for this association. Encephalic, facial, and cranial congenital defects are common and can affect prognosis; 17 patients have other malformations patterns, and they can belong to a different group of malformations. PMID- 1305395 TI - [Intrahospital infections at a neonatal service]. AB - This study is about the importance and mechanisms of the nosocomial infections, specially in newborn babies of the "Hospital General del Centro Medico La Raza del IMSS". We studied 461 newborns of which 53 (11.49%) developed one or more intrahospitalary infections. The rate of intra-hospital infections was 18.40%, mainly due by septicemia, infections of the surgical wounds, and respiratory tract infections. The gramnegative bacterias were predominant. Also were found Staphylococcus aureus and Staphylococcus epidermidis frequently. We give some preventive advice. PMID- 1305397 TI - [Aneurysm of the Galeno's vein: report of a case]. AB - Some aspects of pathophysiology, diagnosis and treatment of gastroesophageal reflux (GER) in children are presented. There is considered a multifactorial syndrome. The objective of this review is present new trends in etiology, diagnostic methods, in a practical point of view, specially in places without sophisticated equipment. Finally it is presented rational therapeutical basis en GER management. PMID- 1305396 TI - [Barotrauma in newborns. Study of 81 cases at a neonatal intensive care unit of a province]. AB - We present 81 patients with diagnosis of air leaks in a Neonatal Intensive Care Unit (NICU). During 6 and a half year period. Air leaks were present in a 7.3% of overall admissions and in 18% in those whom received mechanical ventilation. We observed pneumothorax in all the patients, accompanied by pneumomediastinum in 12% and with interstitial emphysema in 7%. Other forms of air leak were present only rarely. Eighty percent of our patients were managed with intrapleural drainage. Almost 40% of events happened after resuscitation of tracheal aspiration management. The concomitant disease most often seen was respiratory distress syndrome (RDS) during it's convalescent period. Most of them had been previously placed in mechanical ventilation. We had a very high death rate, most significant in the group with weight less than 2,500 g in which 80% died. An analysis between our findings and those in literature was made. PMID- 1305398 TI - [Gastroesophageal reflux disease]. PMID- 1305399 TI - [A simple procedure for umbilical catheterization]. PMID- 1305400 TI - Simple in vivo bioassay without radioisotopes for recombinant human erythropoietins. AB - A simple in vivo bioassay suitable for routine testing of quality control of recombinant human erythropoietin (rHuEPO) analogues was developed. The assay took four days, normal mice were used and radioactive compounds were not needed. EPO activity was measured by the increased number of some part of reticulocytes which increased specifically and dose-dependently by the injection of rHuEPO. They were considered to be mostly immature reticulocytes and were counted as the residual particles from blood cells after treatment with a hemolysing reagent. These particles could be counted by conventional automated microcell counters. The assay procedure was simple and easy. The sensitivity, reliability and reproducibility of this method were acceptable for routine in vivo bioassay of rHuEPOs. This method was economical, and can be used instead of the existing bioassays for rHuEPOs. PMID- 1305401 TI - In vivo biological activities of recombinant human erythropoietin analogues produced by CHO cells, BHK cells and C127 cells. AB - The in vivo biological activity of four pharmaceutical preparations of recombinant human erythropoietin was compared. Two of the erythropoietins were produced by Chinese hamster ovary cells, CHO-K1, and the others were produced by mouse mammary cells, C127, and baby hamster kidney cells, BHK-21. The activities of the analogues were estimated by a simple cell counting method with conventional automated microcell counters. The amounts of these analogues gave straight logarithmic dose-response curves when plotted against the count of particles resistant to hemolysing reagent, which particles were mostly immature reticulocytes. The lines from the four analogues were parallel to each other. The relative activities of these analogues were 1.02, 1.19 and 1.21 when one of the analogues was arbitrarily used as the standard. These differences in the extent of the activity were not significant. Thus, the four recombinant human erythropoietin analogues, produced by four different mammalian cell lines, expressed the same biological potencies in vivo corresponding to their units, and the units used up to now by the manufacturers are equivalent. These results also draw the conclusion that the new simple in vivo bioassay can replace the existing accepted assay methods. PMID- 1305402 TI - Assay for measuring relative potency of leptospiral bacterins containing serovar pomona. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of leptospiral antigen in bacterins containing Leptospira interrogans serovar pomona type kennewicki. A monoclonal antibody (MAb), 2D7, which is directed against a surface antigen on whole cells of L. interrogans serovar pomona type kennewicki, was used in the assay. The capture of antigen in bacterins by a polyclonal antiserum was followed by the addition of the 2D7 ascites fluid, an anti-mouse conjugate and substrate. Biologicals evaluated with this system included preparations containing type kennewicki antigen (homologous) and those not containing type kennewicki antigen (heterologous). Heterologous bacterins gave optical density (OD) values comparable to those of blank wells. Homologous bacterins yielded OD values equal to or greater than those of the National Veterinary Services Laboratories (NVSL) reference pomona bacterin. The relative potencies (RP) of 84 licensed commercial Leptospira pomona bacterin serials were evaluated against the NVSL reference pomona bacterin using the NVSL Relative Potency computer program. Random samples of 1, 2, 3 and 5 ml dose products were selected for evaluation with this system. All products tested passed the hamster potency assay required for leptospiral bacterins. This ELISA system enables detection of antigen in bacterins containing L. interrogans serovar pomona type kennewicki and demonstrates the potential for in vitro testing of leptospiral bacterins. PMID- 1305403 TI - Swedish inactivated polio vaccine: laboratory standardization and clinical experience over a 30-year period. AB - Swedish inactivated polio vaccines have contained per single human dose a mean amount of viral antigen equivalent to 1 x 10(7.5) CCID50 of type 1, 1 x 10(7.4) of type 2 and 1 x 10(7.8) of type 3 produced on primary monkey kidney cells. Potency tests were made in comparison with an equivalent amount of live virus suspension of all three types. Validation of tests has been based on the response to type 1 only. Based on clinical experience with vaccine lots from 1957 and the establishment of the second live reference virus suspension in 1966, the minimum limit of immune response in guinea-pigs--expressed in extinction values--was decided as 1.5 for type 1 and type 3, and 1.0 for type 2. The potency test method used since 1959 in Sweden was two subcutaneous injections 2 weeks apart using 10 guinea-pigs per dilution and blood collected 1 week thereafter. Potency tests made according to European Pharmacopoeia revealed a somewhat lower value for type 2. D-antigen content in Swedish vaccines was low, however, the Swedish vaccine has protected against many episodes or outbreaks of wild virus in Sweden and immunized individuals elsewhere in the world. For the Swedish population a clear cut clinical motivation for requiring a higher potency for type 2 as required in the European Pharmacopoeia or increased levels of D-antigen in the final product has not been presented. It was concluded that the European Pharmacopoeia method did not distinguish between doses of 0.5-1.0 ml. The minimum limit extinction value for type 2, i.e. 2.0 seemed to high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305404 TI - The modified leukocytosis promoting factor (LPF)-test: a valuable supplement to the mouse weight gain (MWG)-test in toxicity control of whole cell pertussis vaccine. AB - For the safety testing of pertussis vaccine, many in vivo assays have been developed, but none of these assays, except the Mouse Weight Gain (MWG)-test, are obligatory. Leukocytosis Promoting Factor (LPF) test, performed in mice, is one of the tests to examine the toxicity. However, due to lack of standardization, this test has not been implemented in the regular safety testing of the vaccine. Our investigations demonstrate that the LPF-test becomes more reproducible and sensitive if preparations are administered subcutaneously on day 0 and and counting of the leukocytes are done on day 6. Therefore, it is suggested to include the revised LPF-test in the quality control panel for the assessment of the toxicity of whole-cell pertussis vaccine. PMID- 1305405 TI - Rabies neutralizing antibody in serum of children compared to adults following post-exposure prophylaxis. AB - Rabies neutralizing antibody concentrations in serum (SRNA) elicited by experimental post-exposure prophylaxis (PEP) regimens are used to assess their potential clinical efficacy. Although PEP with human rabies immunoglobulin (HRIG) plus human diploid-cell culture vaccine (HDCV) is almost completely protective, the limited availability of these components has stimulated the search for alternative regimens. Since 33% to over 60% of PEP is administered to children, a need exists for data on the SRNA response to HRIG plus HDCV in children, to be used to assess the potential value of alternative PEP treatments. We measured SRNA by the rapid fluorescent focus inhibition test on days 0, 1, 3, 7, 14, 28, 56 and 90 after initiation of PEP with HRIG (20 IU/kg) and HDCV (1.0 ml on day 0, 3, 7, 14, 28) in 10 children [8 +/- 4 (mean +/- SD) years of age] and 32 adult control patients (38 +/- 16 years of age). Early, uniform appearance of SRNA was observed with no differences between groups. These data are consistent with the demonstrated efficacy of PEP with HRIG plus HDCV in children as in adults and provide results that can be used for initial evaluation of experimental pediatric PEP regimens in the future. PMID- 1305406 TI - Rabies vaccine standardization: International Collaborative Study for the Characterization of the fifth International Standard for Rabies Vaccine. AB - A collaborative study was carried out to establish a replacement for the International Standard for Rabies Vaccine, the stocks of which are exhausted. Three rabies vaccines for human use derived from different rabies virus strains and prepared on different cell culture substrates were compared with the International Standard for Rabies Vaccine using in vivo and in vitro assay methods in a collaborative study involving 14 participants. The proposed fifth International Standard (PISRAV) which was derived from the same virus strain as the present international standard preparation, the Pitman Moore (PM) strain, was found to be approximately twice as potent relative to the International Standard in immunogenicity assays as in antigenicity assays. On the other hand another vaccine, derived from the LEP strain, was considerably more potent in antigenicity assays than in immunogenicity assays. The glycoprotein of the proposed replacement standard measured in antigenicity assays appeared to be stable at +37 degrees C for 245 days, whereas the immunogenicity of the proposed replacement vaccine was sensitive to this heat treatment and the vaccine lost 66% of its immunogenic potency. The results of this study indicate that the NIH protection test should continue to form the primary basis for potency assay of rabies vaccine as glycoprotein content does not appear to correlate with immunogenic potency for different types of vaccine. The vaccine coded PISRAV has been established as the fifth International Standard for Rabies Vaccine and a potency of 16 International Units of Rabies Vaccine (based on the immunogenicity assays) assigned to the contents of each ampoule. Each ampoule has also been assigned a unitage of 10 IU of PM Rabies Virus Glycoprotein and 135 IU of PM Rabies Virus Ribonucleoprotein. PMID- 1305407 TI - What is a unit of biological activity? PMID- 1305408 TI - Tuberculosis--the next plague? PMID- 1305409 TI - The great pretender. PMID- 1305411 TI - The 100th day case disc. PMID- 1305410 TI - A peptide family being re-united: the angiotensins coming in from the cold. AB - The renin-angiotensin-aldosterone system is now considered to be far more complex than previously thought when the vasoconstrictor and other physiological effects of the octapeptide angiotensin II in the circulating blood were emphasized. The reasons for this altered viewpoint, involving angiotensins other than the octapeptide in the regulation of blood pressure, water and electrolyte homeostasis, are briefly advanced and discussed. PMID- 1305412 TI - The mobile hospitals of the British Red Cross and the Order of St. John and their role in the Rotterdam typhoid epidemic 1945. PMID- 1305414 TI - Rheumatology and its inception in the South West. PMID- 1305413 TI - Factors which predispose elderly patients to develop peptic ulcer disease. PMID- 1305415 TI - Sir William Osler, Oxford and 'The open arms'. PMID- 1305416 TI - Reaching special populations with breast and cervical cancer public education. AB - With passage of the Breast and Cervical Cancer Mortality Prevention Act of 1990, significant activity has emerged in the development, implementation, and evaluation of breast and cervical cancer screening programs targeting underserved populations. This activity has prompted health educators and program planners to identify barriers to breast and cervical cancer screening specific to low-income and minority women, those traditionally underserved by cancer control programs, and to develop strategies that address these barriers. The authors reviewed current knowledge regarding barriers to breast and cervical cancer screening and public education interventions that address them. The results and implications for program planning activities are presented. PMID- 1305417 TI - Knowledge, attitudes, and practices of breast and cervical cancer screening among Vietnamese women. AB - The Vietnamese are the fastest-growing Asian/Pacific Islander ethnic group in California. Data from Vietnam and elsewhere suggest that cervical cancer and breast cancer are major contributors to cancer morbidity and mortality among Vietnamese women. However, little is known about the cancer knowledge and screening practices of Vietnamese women. Using a structured 57-item written questionnaire, we conducted a mailed survey of 400 randomly selected Vietnamese adult women in San Francisco. Overall, 107 women responded (31%). Of the respondents, 54 (52%) indicated that there was little one could do to prevent cancer. More than a third (39%) thought that breast or cervical cancer could be caused by poor hygiene, and about one-third (29%) thought that these cancers could be contagious. Although virtually all (97%) had heard of cancer, one-third did not know that a breast lump could be a sign of breast cancer (37%) or that abnormal vaginal bleeding could be a sign of cervical cancer (39%). Many (55%) did not know that family history was a risk factor for breast cancer and three fourths (74%) did not know that having multiple sexual partners was a risk factor for cervical cancer. Fourteen (13%) had not heard of breast self-examination. Of 31 women aged > or = 40, 10 (34%) had never had a mammogram, and of 92 women aged > or = 18, 50 (54%) had never had a Papanicolaou test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305418 TI - Breast and cervical cancer screening in minority populations: a model for using lay health educators. AB - Although mammography and the Pap smear have significantly reduced US deaths related to breast and cervical cancers, screening prevalence and survival rates for both diseases are disproportionately lower among minority women. This model program outlines techniques for recruiting and training minority women to serve as lay health educators who can effectively deliver preventive health care information to their peers. Lay health educators have three primary functions: to serve as mediators between minority women and health agencies, to establish a social network, and to offer social support. When properly recruited and trained, these educators can bridge the gap between health professionals and the community as well as help health professionals to better understand community and individual concerns about cancer. The goal is to increase the detection, prevention, and treatment of breast and cervical cancers in minority communities and thus decrease related deaths. An ongoing intervention by the Arizona Disease Prevention Center, targeting Yaqui Indian and Mexican-American women aged 35 and older, illustrates specific elements of the model. PMID- 1305419 TI - Glycosylation of pituitary hormones: a necessary and multistep control of biopotency. PMID- 1305420 TI - Efficient catalysis by pyridinium sulfonate in glycosylation involving an oxazoline intermediate derived from per-O-acetyl-N-acetyllactosamine and N,N' diacetylchitobiose. PMID- 1305422 TI - Anti-GM3-lactam monoclonal antibodies of the IgG type recognize natural GM3 ganglioside lactone but not GM3-ganglioside. AB - Immunization of mice with a synthetic GM3-lactam-BSA (bovine serum albumin) conjugate (designed to emulate the corresponding natural GM3-lactone conjugate), followed by fusion of splenocytes with myeloma cells, gave rise to more than 300 monoclonal hybridomas producing antibodies to GM3-lactam-BSA, which did not react with Glc-BSA and BSA. Eight antibody clones were randomly chosen from the positive 300 hybridomas. The eight clones, all belonging to the IgG class, were unreactive against GM3-ganglioside, whereas two antibodies (P5-1 and P5-3, both IgG1, kappa) reacted with GM3-ganglioside lactone. Binding of these two antibodies to the GM3-lactam-BSA conjugate was inhibited by soluble glycosides of GM2-, GM3-, and GM4-lactam and by GM3- and GM4-lactam, respectively, but not by Gb3 or asialo-GM1 and GM2-saccharides. A third antibody (P3; IgG2b, kappa) was inhibited by GM2-, GM3-, and GM4-lactam, but did not recognize GM3-ganglioside lactone. PMID- 1305421 TI - Use of large-scale hydrazinolysis in the preparation of N-linked oligosaccharide libraries: application to brain tissue. AB - In this report, we describe the preparation of a library of N-linked glycans from whole murine brain obtained by the large-scale hydrazinolysis of an acetone powder of the tissue followed by chromatographic procedures. 84% of the characterized oligosaccharides were found to be anionic, the remainder neutral. The anionic species were successively neutralized by neuraminidase (29%), aq. hydrofluoric acid (30%), and methanolysis (26%), indicating that approximately equal portions were sensitive to desialylation, dephosphorylation and desulfation, respectively. The presence of the sulfated fraction was confirmed by direct 35SO4 metabolic labelling. A residual partially characterized fraction was found to be anionic through possession of carboxylic acid groups, unrelated to sialic acid. The purified oligosaccharides, in the absence of their original protein conjugates, were shown to retain those immunological characteristics essential for recognition by a specific monoclonal antibody, LS (412), that is known to recognize a carbohydrate epitope present on a number of neural adhesion molecules and functional in neural cell adhesion. These properties confirm the viability of scaling up the size of the hydrazinolysis procedure and adapting it to whole tissue for the production of glycan libraries and for the probing of structures of interest. PMID- 1305423 TI - Characterization of a glucuronyltransferase: neolactotetraosylceramide glucuronyltransferase from rat brain. AB - The properties of a rat brain glucuronyltransferase, which is presumed to be associated with the biosynthesis of the HNK-1 epitope on sulfoglucuronyl glycolipids, are described. The enzyme required divalent cations for reaction, with maximal activity at 10 mM Mn2+, and exhibited a dual optimum at pH 4-5 and pH 6 depending upon the buffer used, with the highest activity at pH 4.5 in MES buffer. This enzyme strictly recognized the Gal beta 1-4GlcNAc terminal structure, and was highly specific for neolacto (type 2) glycolipids as acceptor. The enzyme was localized specifically in the brain, and was barely detected in other issues, including the thymus, spleen, liver, kidney, lung, and sciatic nerve fibres. Phosphatidylinositol and phosphatidylserine increased the enzymatic reaction 4.4- and 2.3-fold, respectively, whereas phosphatidylcholine slightly decreased the rate. PMID- 1305424 TI - Glycosphingolipid expression in spontaneously aborted fetuses and placenta from blood group p women. Evidence for placenta being the primary target for anti-Tja antibodies. AB - A 12-week-old fetus and one 17-week-old fetus + placenta were obtained after spontaneous abortions from two women of blood group p. The 17-week-old fetus was dissected into intestine, liver, brain and residual tissue. Nonacid glycosphingolipid fractions were prepared from the tissues. Glycolipid characterization was carried out using thin layer chromatography immunostained with monoclonal antibodies and bacteria and by 1H NMR spectroscopy and mass spectrometry. In the placental fraction substantial amounts of globotetraosylceramide (P-antigen) and globotriaosylceramide (Pk-antigen) were identified. In contrast, the fetuses contained only trace amounts of these structures, as revealed by immunostaining. These results indicate that the primary target for the antibodies of the anti-Tja serum is the placenta tissue, resulting in termination of the pregnancy. PMID- 1305425 TI - [The pharmacological characteristics of the new anticholinesterase drug aminostigmine]. AB - The pharmacological properties of a new drug approved in the USSR for the treatment of cholinolytics poisonings are described. The drug is as active as physostigmine. However, its action is longer. Aminostigmine exhibits marked central effects, which forms the basis for its use for elimination of brain dysfunctions caused by choline blockers. PMID- 1305426 TI - [The nooglutil correction of functional disorders of the central nervous system caused by prenatal alcoholization in rats]. AB - Administration of ethanol (5 g/kg/day, per os) to the pregnant rats evoked delayed impairments of the learning and memory in the offspring. Prenatal alcoholization of the animals attenuated the habituation of the exploration behavior in open field, impaired acquisition and retention of active avoidance in a shuttle box, increased slow activity of the EEG spectrum power, disturbed the function of the serotoninergic system in the brain cortex and of the dopaminergic system in the hippocamp. The new nootropic drug nooglutyl (N-5/hydroxynicotinoyl/ L-glutamic acid) administered in a dose of 25 mg/kg/day from the 8th to the 20th day of life prevented the above-mentioned delayed disturbances of higher integrative functions and biochemical processes in rat brain. PMID- 1305428 TI - [The search for new anticonvulsant agents based on nicotinamide]. AB - The electron structural analogs nicomorpholine and azethylnicotinate possessing a high anticonvulsant activity in experiment were synthesized on the basis of nicotinamide. The new substances antagonized the convulsant effect of corasole in the doses less by a factor of 10 than nicotinamide, with the therapeutic protective index of the test agents being 3-4 times higher than that of nicotinamide and being equal to the index of phenobarbital and diazepam. Analysis of the anticonvulsive activity with the aid of pro- and anticonvulsants disclosed that nicotinamide and its analogs are more effective in relation to bikukullin, thiosemicarbazide and picrotoxin than to corasole. Nicomorpholine like nicotinamide is capable of suppressing the epileptic foci in various zones of the cerebral cortex. The data obtained evidence that the spectrum of the activity of nicotinamide and its analogs differ from that of the classic anticonvulsants and antiepileptic drugs of the diphenin and phenobarbital series, resembling, to a greater degree, benzodiazepine tranquilizers with the predominant influence on the GABA-ergic system. PMID- 1305427 TI - [The neurotropic properties of new 4,4-di-substituted derivatives of 1 methylpiperidine]. AB - Experiments on small laboratory animals were made to study local anesthetic, antinociceptive and antihypoxic properties of 6 new derivatives of 1 methylpiperidine. A substance coded phi AB-8 (1-methyl-4-vinylethynil-4-benzoyl hydroxypiperidine hydrochloride) was found to exert a pronounced local anesthetic and an antihypoxic actions. PMID- 1305429 TI - [The increased sensitivity of rats to ouabain in the acute stage of heart failure]. AB - A study was made of the response of the cardiovascular system to the cardiac glycoside ouabain, using original experimental acute heart failure that developed as a result of coronary vessel embolization with 15 microns radioactive microspheres introduced into the cavity of the left ventricle during occlusion of the ascending aorta. To examine the general and regional hemodynamics, an isotope exchange method was employed. 48 hours after coronary vessel embolization the rats appear more sensitive to the action of ouabain as compared to the sham operated animals. This shows up in a more pronounced vasoconstriction in some organs, leading to a noticeable increase of the general peripheral resistance and arterial pressure. High sensitivity of the cardiovascular system to ouabain makes this effect transform very rapidly to the toxic one. PMID- 1305430 TI - [The central and peripheral components in the mechanism of action of urapidil]. AB - Effects of two doses of urapidil (0.6 mg/kg and 1.2 mg/kg, i.v.) on the sympathetic nervous activity (renal nerve) and sensitivity of the chronotropic and sympathetic components of the baroreceptor reflex were studied in experiments on awake Wistar rats. Urapidil did not change significantly the baseline sympathetic nervous activity. The sensitivity of the sympathetic baroreceptor reflex tested by phenylephrine was significantly enhanced and that tested by nitroprusside was significantly inhibited by urapidil. The sensitivity of the heart rate baroreceptor reflex tested by phenylephrine remained unchanged whereas that tested by nitroprusside was significantly inhibited by urapidil. It is concluded that urapidil changes the sensitivity of the baroreceptor reflex via the central mechanism of action. PMID- 1305431 TI - [The anticoagulant action of a factor from the nondialyzed fraction of the ammoniacal extract of the lungwort, Pulmonaria mollissima]. AB - It has been established that a non-dialyzed fraction of ammoniacal extract from P. molissima contains an anticoagulant-glycopeptide. In in vivo experiments, it produces stable hypocoagulemia, primarily blocking fibrin self-assemblage, and prevents the animal's death from thromboplastinemia. It has been found that the aforesaid action does not exert any adverse effect on the blood contents, arterial pressure, respiration or urinary renal function. PMID- 1305432 TI - [Changes in the endogenous hormonal background due to anabolic steroids]. AB - Studies into the effects of metandrostenolone and ecdisterone, anabolic steroids of different classes, on the content of hormones in blood plasma made it possible to establish that metandrostenolone produces appreciable changes in the hormonal background: a short-term increase in the content of corticosterone but a decline in the concentration of somatotropic hormone (STH). The long-term administration of metandrostenolone brings about a reduction of the content of testosterone. Unlike metandrostenolone, ecidsterone provoked but an increase in the content of corticosterone both on single and long-term administration. It is concluded that the rise of the content of corticosteroids in blood plasma under the influence of the tested drugs may be a factor favoring mobilization of biochemical processes in skeletal muscles in response to physical exercise. Meanwhile the change in the corticosterone:testosterone:STH ratio in blood may cause side effects due to the long-term use of metandrostenolone and other anabolic derivatives of androgens. PMID- 1305433 TI - [The efficacy of quercetin in alloxan diabetes]. AB - It has been established that quercetin in doses of 10 and 50 mg/kg promotes normalization of the level of glycemia and blood coagulation, increases liver glycogen content, reduces high blood serum concentrations of cholesterol and low density lipoproteins, seen in diabetes. In some cases, the efficacy of quercetin exceeds that of chlorpropamide and dry Eleutherococcus extract in white rats with alloxan diabetes. PMID- 1305434 TI - [The correction of energy metabolism disorders in hypoxia by using vitamin K]. AB - A study was made of the possibility of correcting respiratory chain function disorders in hypoxia by means of the naphthoquinone derivative vitamin K3. The antihypoxic activity of that compound is defined by its donor-acceptor properties and its capability to shunt the electron flow from NADH to CoQ. The effect is more pronounced in the tissues that oxidize mostly the NAD-dependent substrates which is related to rapid inactivation of the given enzymatic complex under hypoxia and correlates with low resistance of the cell using the NADH-oxidase pathway of oxidizing energy substrates to oxygen deficiency. PMID- 1305435 TI - [An analysis of the intracellular distribution of glucocorticoid hormones by using a mathematical model]. AB - A mathematic model depicting the interaction of glucocorticoids with the target cell is proposed. Specific features of cortisol and dexamethasone distributions in thymocytes in a wide range of hormonal concentrations have been analyzed. It has been established that specific action of glucocorticoids is dependent on the binding affinity and the number of the binding sites of hormones in the topographically different cell receptor systems (intracellular and membrane glucocorticoid receptors). PMID- 1305436 TI - [The immunity indices of the progeny of white rats antenatally exposed to prodigiozan]. AB - A study was made of the effect of prodigiosan administered during pregnancy on the immunity system of the offspring. Material changes in the immune response to foreign antigens were found to be determined by the day of pregnancy on which prodigiosan had been administered. PMID- 1305439 TI - [The problem of fever and its elimination in children]. AB - This is the brief review of literary data about mechanism of development and means of removal the fever, in the main order to render the first symptomatic aid for children. Special attention paid to combinations of drugs with acupuncture. Elucidation of mechanisms of realisation antipyretic effects of acupuncture and interactions of drugs and acupuncture is the most actual problems for research. PMID- 1305437 TI - [The effect of ziksorin on the development of experimental food anaphylaxis in guinea pigs]. AB - A study was made of the effect of zixorin, an inductor of liver cytochrome P-450, on the intensity of the immediate type allergic reaction--active food anaphylaxis in response to ovalbumin in guinea-pigs. Intraperitoneal injection of zixorin in a dose of 50 mg/kh for 3 days before administration of the antigen resolution dose was found to lower 2,3-fold the level of lethal outcomes due to the anaphylactic shock. It is suggested that zixorin may be used in multimodality treatment of food allergy. PMID- 1305438 TI - [The results of the therapeutic monitoring of piracetam in parturients and newborn infants]. AB - Overall 30 women in childbirth with preeclampsia and fetoplacental dysfunction received piracetam solution which was given initially in a dose of 5 g by intravenous drip, rapidly since the onset of labour and then every 2 hours till the end of labour in a dose of 2 g by jet injection. This made it possible to increase fetus resistance to hypoxic conditions. The concentrations of piracetam within the range of 60-80 g/l in the blood of women in childbirth should be viewed as minimum therapeutic. A single daily intramuscular injection of piracetam (50 mg/kg) into neonates with encephalopathies may build up blood concentrations equal to 25-60 mg/l after 2 hours. The drug is not detectable in the blood by the moment the next injection is given. PMID- 1305440 TI - [The efficacy of vitogepat and sirepar in combination with karsil in chronic liver lesions]. AB - It has been shown in experiments on white rats that chronic (for one month) intoxication with CCl4 and C2H5OH results in liver injury. It manifests by activation of aminotransferases (ALT, AST) and alkaline phosphatase in blood serum, initiation of lipid peroxidation, depletion of the liver pool of reduced glutathione, and suppression of bile production. The liver preparations (sirepar and vitohepat) reduce hepatotoxicity of the poisons in question. The use of vitohepat and sirepar in combination with carsil potentiated hepatoprotective and antioxidative activity of the liver preparations. PMID- 1305442 TI - [Anthelmintic agents]. PMID- 1305441 TI - [The advantages of benzonal as an inducer of the liver mono-oxygenase enzyme system compared to phenobarbital]. AB - It is stated that phenobarbital used as the most potent inductor of the monoxygenase enzymic system of the liver in different pathologies has substantial side effects. In this connection the search of active inductive agents devoid of phenobarbital deficiencies is an important issue. Zixorene, a Hungarian drug developed to solve the problem, is weak as an inductor and has deficiencies of its own. A fitting substitute for phenobarbital is benzonal which is not inferior to phenobarbital in inductive activity but lacks its drawbacks. It is used both as a hypobilirubinemic agent and a drug restoring a disordered monohygenase system of the liver in different pathologies. Benhonal is metabolized in the gastrointestinal tract and the liver generating an active metabolite of phenobarbital. It is suggested that slow formation of phenobarbital in small quantities determines its more optimal interaction with the corresponding hepatic receptors resulting in the appearance of a marked inductive action while side effects are significantly decreased. PMID- 1305443 TI - [Central nervous system stimulants as nonspecific antagonists of morphine-induced respiratory depression]. AB - The respiratory effects of pymadin, amiridine, thyrotropin-releasing hormone (TRH), its analog RGH 2202, and pentetrazol and their interaction with morphine were studied in anesthesized rats. During intravenous injection or local application to the medulla oblongata, pymadin, amiridine, TRH and RGH 2202 were shown to enhance the respiratory activity of the diaphragm and to abolish its morphine-induced inhibition. TRH and RGH 2202 proved to be the most potent and safe antagonists of morphine-induced respiratory depression. These agents given in the doses sufficient to completely abolish morphine-induced respiratory depression unchanged its antinociceptive activity. Pentetrazol in the tested dose range failed to increase diaphragmatic respiratory activity or to eliminate its depression induced by morphine. PMID- 1305444 TI - [The effect of cholinergic-potentiating and cholinergic-blocking agents on reparative processes in the damaged gastric mucosa of rats]. AB - Rat experiments have indicated that increased lipid peroxidation in gastric tissue occurs with formation of cryogenic gastric ulcers. The use of methacin alone, 1 mg/kg i.p., and in combination with proserinum, 0.1 mg/kg, s.c., metamisyl alone, 1 mg/kg, i. p., and in combination with galanthamine hydrobromide, 1 mg/kg, s. c., result in acceleration of reparative process in the rat gastric walls and normalization of gastric tissue malonic dialdehyde levels. Methacin in combination with proserinum has been found to be most beneficial. PMID- 1305445 TI - [The effect of N-methyl-D,L-aspartic acid on the nociceptive reaction of mice]. AB - Intraperitoneal NMDLA was pharmacologically studied in mice for effects by using the hot-plate test. The agent given in a subconvulsive dose of 50 mg/kg showed a biphasic action: 5 minutes after administration there was hyperalgesia (Phase I) followed by hypoalgesia (Phase II) 15 minutes later. The effects of phencyclidine, ketamine, morphine, naloxone, bromocriptine and isradipine on NMDLA's analgetic action were also examined. Bearing in mind the fact that the action of NMDLA is decreased by isradipine in Phase I and by receptor-acting agents in Phase II it is suggested that there is a great difference in the patterns of the two phases of the analgetic action of NMDLA systemically used. PMID- 1305446 TI - [The pharmacokinetics and pharmacodynamics of the prolonged-action beta adrenoblocker nadolol at rest after a single administration to hypertension patients]. AB - The pharmacokinetics and pharmacodynamics of nadolol given in a single dose of 80 mg to 17 patients with mild hypertension were studied by echocardiography at rest. The major pharmacokinetic parameters for nadolol did not differ greatly from those reported in the literature and obtained from volunteers. No correlation was found between endogenous creatine clearance and renal nadolol clearance. How the hemodynamic effect developed and whether it was related to blood nadolol concentrations in time after single administration were followed up and discussed. There was a significant decline in blood pressure 2 hours after the drug. There was a clock-wise hysteresis in the relationship between the changes in cardiac output and nadolol levels. Changes in blood pressure were shown to significantly correlate with those in cardiac output. PMID- 1305447 TI - [The role of prazosin in regulating cardio- and hemodynamics in the early stage of experimental lung-heart failure]. AB - Canine experiments have shown that prazosin used in the course of therapy for pulmonary hypertension and abolition of heart overload substantially enhanced myocardial contractility and relaxing properties of the both ventricles and improved cardiac pump function. PMID- 1305448 TI - [The effect of prostacyclin and its synthetic analog MM-706 on kidney function in corrosive sublimate-induced nephropathy]. AB - The effects of prostacyclin and its stable analogue MM-706 on renal function were examined in rats with sublimate nephropathy. Prostacyclin was shown to attenuate renal dysfunctions by increasing glomerular filtration rate and water and salt reabsorption. MM-706 produced more pronounced protective effects and restored the filtration and reabsorption up to the level observed in control rats. PMID- 1305449 TI - [The efficacy of substances with antihypoxic action in experimental hyperlipidemia]. AB - Experiments on rats, guinea pigs and rabbits with hyperlipidemia induced by high cholesterol diet have revealed that the specific antihypoxic drug oliphen has hypolipidemic effect which is least pronounced in oral GABA. Oliphen causes a significant increase in alpha-cholesterol (antiatherogenic lipoprotein cholesterol) decreased by hyperlipidemia. It is suggested that oliphen improves hepatic receptor-dependent uptake and atherogenic lipoprotein degradation. PMID- 1305450 TI - [S. V. Anichkov--man and scientist (on the centenary of his birth)]. AB - The paper is devoted to a brief review of the research and public activities of Professor Sergei V. Anichkov; the prominent Soviet pharmacologist. He was Hero of Socialist Labour, V. I. Lenin and State Prize winners and Academician of the USSR Academy of Medical Sciences. It also summaries the main biographic data on the scientist and his theoretical and practical achievements in various areas of pharmacology. Great emphasis is laid on S. V. Anichkov's scientific school and his work in the Department of Pharmacology (he was head of the Department from 1948 to 1981), Institute for Experimental Medicine, USSR Academy of Medical Sciences. PMID- 1305451 TI - [The hypolipidemic action of water-soluble enterosorbents of cholesterol and bile acids in an experiment]. AB - Experiments on rats, guinea pigs and rabbits with experimental dyslipoproteinemia have revealed that the new water-soluble high-molecular weight polymers containing digitonin (ED) or a quaternary nitrogen atom (EA) have a more marked hypolipidemic action than cholestyramine and normalize lipoprotein metabolism. The digitonin-containing enterosorbent has been shown to decrease the absorption of 4-14C-cholesterol, while the nitrogen-containing enterosorbent diminishes the absorption of 3H-cholic acid. PMID- 1305452 TI - [The hypolipidemic activity of natural substances]. AB - Experiments on guinea pigs and rats have revealed that thiazole derivatives of isoflavone has a beneficial effects on disturbed lipid and lipoprotein metabolism. New phospholipid complexes enriched with vitamins have been demonstrated to produce a hypolipidemic effect. Sulfated chitosans decrease lipid infiltration of the liver and elevate serum high density lipoprotein levels in rats. PMID- 1305453 TI - [The immunomodulating action of riboxin during physical loading]. AB - Administration of riboxin to Wistar rats which had no exercise increased the development of a humoral immune response, but failed to affect the manifestations of delayed hypersensitivity induced by sheep red cells. Riboxin given to swimming rats intensified the development of two immune response types. The agent enhanced splenic cell release of suppressive and helper agents in swimming rats and reduced the responsiveness of the immune system to suppressive agents liberated by splenocytes during exercise. The cells of the swimming rats' immune system were sensitive to the helper agent liberated by splenocytes after riboxin administration. PMID- 1305454 TI - [A metabolic study of the synthetic glucocorticosteroids prednisolone and dexamethasone in the body of white rats and in in-vitro reactions]. AB - The metabolism of the synthetic steroidal hormones prednisolone and dexamethasone was studied in albino rats and in in vitro microsomal oxidation system by using high performance chromatography and radioactive tracers. Dexamethasone was found to be metabolically stable. The first step of prednisolone biotransformation is formation of prednisone during the NADPH-dependent reaction catalyzed by microsomal enzymes. Conditions were created for isolating the ultimate prednisolone metabolite formed in the rats' body by using HPLC. PMID- 1305455 TI - [The action of acute alcoholic intoxication on the antioxidant system and creatine kinase activity in the brain of rat embryos]. AB - The activity of superoxide dismutase (SOD) was enhanced in the brain of 14-day rat embryos 1 and 3 hours after single administration of ethanol to pregnant rats. Concurrently, the levels of lipid peroxidation were changing in these periods. Ethanol, 1 g/kg, increased LPO levels in the 14-day embryonic brain, whereas its dose of 3 g/kg decreased them. It is concluded that with single administration of ethanol, free-radical processes are activated in the embryonic brain. It is suggested that the activity of creatine kinase decreases concurrently with an increase in SOD activity due to the damaging action of superoxide radicals on the enzyme molecule. PMID- 1305457 TI - [The presence of quinolinic acid in the structures of the rat brain]. AB - The brain tissue extracts from chronically alcoholized (15% ethanol intake for more than 18 months) rats were studied by mass spectrometry. The mass spectra for the striatum of control and alcohol-consuming rats were identical, while those for the hippocampus showed a significant difference: a great increase in the intensity of peaks typical of mass spectra for quinolinic acid. PMID- 1305456 TI - [The effect of the inhalation of ethanol and acetone on the indices of the antioxidant protection system and on lipid peroxidation in the brain tissue and blood serum of rats]. AB - Ethanol or acetone inhalation resulted in a reduction in motor activity in rats, affecting largely their explorative behavior. The biochemical parameters of free radical processes (catalyse and SOD activities, LPO levels) remained unchanged in the inhaling animals. Ethanol or acetone inhalation caused a significant decrease in blood catalyse activity and serum LPO levels. The acetone- and ethanol-induced changes in the activity of ceruloplasmin were heterodirectional. It can be concluded that it is useful to study the biochemical parameters of serum free radical processes and to employ the findings in the therapy of inhalation toxicomanias. PMID- 1305458 TI - [The comparative characteristics of the effect of piracetam peptide analogs on the recovery of conditioned reflex activity in animals following damage to the frontal cortex and the electrophysiological characteristics of the brain integrative activity]. AB - The time course of recovery of a conditioned avoidance response (CAAR) after extirpation of brain frontal regions was examined in rat experiments. The reference nootropic drug piracetam given in a dose 200 mg/g for 9 days after surgery promoted CAAR recovery. The original peptide analogue of piracetam- pyroglutamyl-D-alanine amide (I)--produced the same effect when given in a dose of 1 mg/kg. Another peptide analogue of piracetam--pyroglutamyl-asparagine amide (II) showed no promoting effect on CAAR recovery after frontal lobectomy. Electrophysiological experiments have demonstrated that I promotes the transcallosal cortical responses to a greater extent than does II. It has been suggested that the most significant promoting effect on the compensatory and recovery process after frontal lobectomy is produced by the nootropic compounds which have a promoting effect on memory trace consolidation. PMID- 1305459 TI - [The effect of vicasol and pelentan on the biopolymers of the periodontium]. AB - Vitamin K (vikasol) and pelentan were examined for their effects of periodontal tissue levels of collagen, hexosamine-containing biopolymers and sialoglycoproteins. During tooth replantation in dogs, vitamin K was demonstrated to elevate the levels of collagen, hexosamine-containing polymers in periodontal tissue by 25.8, 19.9, and 36.1%, respectively, whereas pelentan lowered the above parameters. PMID- 1305461 TI - [The psychopharmacology of narcotics: a preclinical study]. AB - Simple and economic tests for estimating addictive potential of drugs using conditioned place preference and intravenous self-administration paradigms have been developed. Various groups of substances were revealed among 12 opioids which differed by their potencies in analgesics and reinforcing tests. Index of "narcological safety" and "addictive index" were proposed for comparative evaluation of therapeutic and adverse (addictive) effects. Using the self administration procedure a group of addictive psychostimulants were investigated and quantitative criteria for the reinforcing action of them were derived. The analgesic and reinforcing effects of morphine have been dissociated by administration of the calcium-channel blocker isradipine. PMID- 1305460 TI - [The effect of diphosphonates on the metabolism of calcium, its regulation and the state of the bone tissue in the modelling of the physiological effects of weightlessness]. AB - The diphosphonates AMOA and OEDP had a positive action on calcium metabolism and regulation and the osseous tissue in tilt-suspension and hypokinetic Wistar rats in 40-60-day experiments. During special regimens of physical training, ksidifon (OEDP) produced preventive effects on calcium metabolism and renal calciuretic function in man during 120-day antiorthostatic hypokinesia and the agent may be recommended for prevention of alterations in mineral metabolism and osseous tissue at long-term bed rest. PMID- 1305463 TI - [A brief outline of the history of the Department of Pharmacology of the I. P. Pavlov Ryazan Medical Institute (1943-1990)]. PMID- 1305462 TI - [A method for studying the effect of drugs on the psychophysiological status and quality of the performance of operators with different skills by using a microcomputer]. AB - Computer method for evaluating the quality of the motivated operator's performance and psychophysiological status was devised and validated. This method can be used for clinical studies of new drugs. PMID- 1305464 TI - [The effect of hormonal systems on the activity of convulsant agents]. AB - The dynamics of convulsive action exerted by Bemegride, 15 mg/kg, and Corasol (Pentamethylenetetrasol, 50 mg/kg, was examined in rat experiments during extirpation of endocrine glands (pituitary, thyroid, adrenals and gonads). Their effects were found to be unequal in various series of experiments: thyroidectomy intensified the nature of convulsive reactions while gonadectomy attenuated them; sex-specific differences in the effects of the agents were insignificant. It has been suggested that the hormone-mediator interaction is essential in the mechanisms of convulsive action of Bemegride and Corasol. PMID- 1305465 TI - Environmental risk factors for nasopharyngeal carcinoma: a case-control study in northeastern Thailand. AB - A case-control study of nasopharyngeal carcinoma was conducted in northeast Thailand, a region which shows an intermediate risk for this neoplasm. The study was conducted to investigate the importance of environmental exposures, particularly salted fish consumption, cigarette smoking, alcohol drinking, and occupational exposure to smoke or dust, as risk factors for the disease. Data from 120 nasopharyngeal cancer cases and the same number of hospital-matched controls indicated that consumption of sea-salted fish at least once a week was a significant risk factor (odds ratio, 2.5; 95% confidence interval, 1.2-5.2). Agricultural workers were also at significantly higher risk (odds ratio, 2.8; 95% confidence interval, 1.3-6.2), and working in agriculture or as a woodcutter was associated with an even higher risk (odds ratio, 8.0; 95% confidence interval, 2.3-28.2). There was no association between nasopharyngeal carcinoma and alcohol drinking or cigarette smoking. PMID- 1305466 TI - Active and passive cigarette smoke exposure and cervical intraepithelial neoplasia. AB - This case-control analysis presents odds ratios for active and passive cigarette smoke exposure and cervical intraepithelial neoplasia of levels II and III (CIN II and CIN III) while controlling for confounders. From 1987 to 1988, 103 biopsy conformed incident cases of CIN II or III and 268 controls with normal cervical cytology were enrolled. Seventy % of cases were cigarette smokers, while only 30% of controls had ever smoked. The adjusted odds ratio for current cigarette smoking was 3.4 (95% confidence interval, 1.7-7.0). The following confounders were included in logistic regression models: age, race, education, number of sex partners, contraceptive use, sexually transmitted disease history, and Pap smear history. The risk of CIN II/III increased with increasing years of cigarette smoking and with increasing pack-years of exposure. Smoking was associated more strongly with CIN III than CIN II. The effect of passive cigarette smoke exposure was explored separately for smokers and nonsmokers and was found not to be consistently associated with CIN II/III when controlling for confounders. PMID- 1305467 TI - Sources of variability in normal CA 125 levels. AB - Two hundred eighty-eight serum specimens from 144 asymptomatic menopausal women were assayed two times each for CA 125. The specimens were randomly assigned to sixteen CA 125 kits. Our purpose was to quantitate the biological variability and the assay variability that occurs at low levels of this tumor marker. All of the subjects had CA 125 values less than 35 units/ml. The total error from all sources was about 13% of the observed values. These findings suggest that single, low CA 125 values are reliable indicators of a woman's true CA 125 value. Clinical trials of ovarian cancer screening that incorporate CA 125 measurements should evaluate the performance of this test at thresholds lower than the usual 35 units/ml. PMID- 1305469 TI - Significant endogenous synthesis of nitrate does not appear to be a feature of influenza A virus infection. AB - There is much concern about the role of nitrate in the formation of carcinogenic N-nitroso compounds. There has been renewed interest in the endogenous formation of nitrate arising as a host response to infection. This study was designed to investigate whether the large increases in nitrate excretion rate reported (6-15 fold) for certain infectious diseases is also a feature of systemic influenza infections. Volunteers were challenged either with an attenuated strain of influenza A virus or with saline; and excreted nitrate was measured in subsequent 24-h urine samples. Both with and without adjustment for potential confounding by dietary and other factors, it was clear that neither mild nor moderate influenza A virus infection resulted in substantial endogenous nitrate biosynthesis since all the variation in urinary nitrate excretion observed was within the range of normal daily fluctuations. It remains possible that a stronger and more consistent nitrate excretion response might be observed in other infectious illnesses with greater systemic disturbance. PMID- 1305468 TI - Linear versus nonlinear models for hemoglobin adduct formation by acrylamide and its metabolite glycidamide: implications for risk estimation. AB - Hemoglobin cysteine adduct levels formed by acrylamide (AA) and its epoxide metabolite glycidamide (GA) as previously determined (Bergmark et al., Toxicol. Appl. Pharmacol., 111: 352-363, 1991) in rats given single injections of AA were used to estimate tissue doses, D = integral of Cdt (area under the concentration curve in the blood compartment), of the two compounds. The data were adapted to linear or nonlinear kinetic models, where the latter model accounted for the Michaelis-Menten kinetics of the metabolic conversion of AA to GA. In the linear model, the first-order rates, k*, of elimination from all processes were estimated to be 0.50 and 0.48 h-1 for AA and GA, respectively. In the nonlinear model, the parametrical values Vmax = 19.1 h-1 and Km = 66 microM for the in vivo metabolic conversion of AA to GA, and k1 = 0.21 h-1 and k2 = 0.48 h-1 for the first-order rates of elimination from all other processes of AA and GA, respectively, were found to give the best fit to the exact dosimetric expressions [formula: see text] Using Equation B, it was estimated that the percentage of AA converted to GA approaches 58% when [AA]o, the initial concentration of AA, approaches zero. The implications for high-to-low-dose extrapolation of toxic effects of the derived mathematical relationships between administered dose and tissue dose are discussed. PMID- 1305470 TI - Simultaneous liquid chromatographic determination of carotenoids, retinoids, and tocopherols in human buccal mucosal cells. AB - Epidemiological and experimental data have suggested that some micronutrients, including various carotenoids, retinoids, and alpha-tocopherol, may have chemopreventive activity against certain types of human cancer. In order to define the role of these micronutrients in cancer prevention, it is necessary to measure their concentrations in the target tissues, since these are critical to the chemopreventive effect. We have developed a sensitive and reproducible high performance liquid chromatography procedure for the simultaneous determination of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, retinol, retinyl palmitate, alpha-tocopherol, and gamma tocopherol in an easily accessible human target tissue, the buccal mucosal cells. This procedure used a gradient of two mobile phases which consisted of acetonitrile, tetrahydrofuran, methanol, 1% ammonium acetate, and butylated hydroxytoluene (in v/v/v/v/w): mobile phase A, 85:5:5:5:0.05; mobile phase B, 55:35:5:5:0.05. The run time, including reequilibration, was 47 min: from 100% A to 100% B in 27 min, remaining at that mobile phase for 10 min, then back to 100% A at 43 min at a constant flow rate of 1.3 ml/min. The high-performance liquid chromatography effluent was monitored at 300, 325, and 452 nm for tocopherols, retinoids, and carotenoids, respectively, with a photodiode array detector. The average recovery was 83% for lycopene and > 92% for others. The precision of the assay for all the compounds was less than 10% in a 1-month period. The micronutrients were extracted by incubating the cells with protease, followed by vortex mixing with 1% sodium dodecyl sulfate in ethanol containing 0.1% butylated hydroxytoluene, and, finally, hexane extraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305471 TI - Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal. AB - Our previous studies showed that phenethyl isothiocyanate (PEITC), a cruciferous vegetable constituent, inhibited the lung tumorigenesis induced by a potent tobacco-specific carcinogenic nitrosamine in animals. These results implicate dietary PEITC as a risk-reducing factor of lung cancers induced by smoking. To define the effect of dietary PEITC on human cancers, a method of measuring its uptake is needed. Since watercress is rich in gluconasturtiin, a glucosinolate precursor of PEITC, it was chosen to be the source of PEITC. Four individuals were asked to eat watercress as part of a breakfast meal, and 24-h urine samples were collected. A urinary metabolite was found, and its identity was confirmed as the N-acetylcysteine conjugate of PEITC by comparison with the synthetic standard using nuclear magnetic resonance and mass spectrometry. A dose-dependent excretion of this conjugate was observed. These results clearly showed that PEITC was released in the human body upon ingestion of watercress and suggest that the N-acetylcysteine conjugate of PEITC may be a useful marker for quantitating human exposure to this anticarcinogen as a tool for epidemiological investigations. PMID- 1305472 TI - Thyroid hormones and duration of ovulatory activity in the etiology of breast cancer. AB - We conducted the present study with the hypothesis that conflicting reports on the association between mild hypothyroidism and breast cancer may be due to failure to consider the potential interaction between thyroid and ovarian hormones. Seventy-three cases of breast cancer and 75 hospital controls were studied. The overall matched multivariate odds ratio of breast cancer for the lowest tertile of free T4 (< or = 1.10 ng/dl) versus the two other tertiles was 1.7 (95% confidence limits, 0.6-5.0). However, there was a statistically significant linear trend (P = 0.04) in the odds ratios for breast cancer related to subnormal free T4 levels across tertiles of duration of ovulatory activity. These results suggest that women combining low levels of circulating free T4 with long duration of ovulatory activity may be at increased risk for this disease. PMID- 1305473 TI - Effect of chemopreventive agents on intermediate biomarkers during different stages of azoxymethane-induced colon carcinogenesis. AB - Chemoprevention of colon cancer is emerging as an alternative to therapy with a broad potential for reducing cancer incidence in defined high-risk groups and the general population. Besides several chemopreventive agents in use and under investigation, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam have been shown to effectively inhibit colon carcinogenesis in rodents. A variety of proliferation-related parameters have been suggested as potential intermediate markers of cancer risk that could be used to monitor the progress of chemoprevention in clinical trials. We have investigated the effect of chemopreventive agents, DFMO, and piroxicam on mucosal ornithine decarboxylase (ODC) and tyrosine-specific protein kinase (TPK) activities during different stages of azoxymethane (AOM)-induced colonic carcinogenesis in male F344 rats in order to examine the plausibility of using these enzymes as intermediate biochemical markers of colon cancer. Groups of male F344 rats were fed modified AIN-76A diets containing 0 or 150 ppm piroxicam or 4000 ppm DFMO and given s.c. injections of AOM dissolved in normal saline at a dose of 15 mg/kg body weight/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then sacrificed at 0, 4, 16, 24, and 32 weeks after AOM or saline treatment, and their colonic mucosa was analyzed for ODC and TPK activities. AOM treatment significantly increased mucosal ODC as well as TPK activities. AOM-induced ODC and TPK activities were significantly suppressed by dietary DFMO progressively at all stages of colon carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305474 TI - Feasibility of a telephone survey to recruit health maintenance organization members into a tamoxifen chemoprevention trial. AB - A large-scale, nationwide tamoxifen chemoprevention trial is currently being planned as a primary preventive strategy against breast cancer. The recruitment of health asymptomatic women into a long-term clinical trial will pose unique recruitment problems. This study examines the feasibility of telephone recruitment from a health maintenance organization population into such a trial. A random sample of 203 women aged 50 and older with a personal family history of breast cancer were contacted by telephone. A structured interview was administered to assess self-perceived risk of breast cancer, willingness to participate in a trial, and anticipated barriers to participation. Of the 203 names generated from the health maintenance organization membership roster 128 (63%) met eligibility criteria and participated in the interview. Forty-five % of the eligible women expressed interest in the tamoxifen trial. Women who felt that their family would support their participation expressed significantly more interest, while concern about possible side effects emerged as potential barriers. We conclude that contact by telephone among health maintenance organization members can identify a significant proportion of women who are interested in primary chemoprevention for breast cancer. Participation rates may be improved by bolstering family support and by addressing concerns about drug toxicity. PMID- 1305475 TI - Correspondence Re: A. I. Neugut et al., differences in histology between first and second primary lung cancer. Cancer epidemiol., biomarkers & prev., 1: 109 112, 1992. PMID- 1305476 TI - Directed movements of ciliary and flagellar membrane components: a review. AB - The ability to rapidly translocate polystyrene microspheres attached to the surface of a plasma membrane domain reflects a unique form of cellular force transduction occurring in association with the plasma membrane of microtubule based cell extensions. This unusual form of cell motility can be utilized by protistan organisms for whole cell locomotion, the early events in mating, and transport of food organisms along the cell surface, and possibly intracellular transport of certain organelles. Since surface motility is observed in association with cilia and flagella of algae, sea urchin embryos and cultured mammalian cells, it is likely that it serves an additional role beyond those already cited; this is likely to be the transport of precursors for the assembly and turnover of ciliary and flagellar membranes and axonemes. In the case of the Chlamydomonas flagellum, where surface motility has been most extensively studied, it appears that cross-linking of flagellar surface exposed proteins induces a transmembrane signaling pathway that activates machinery for moving flagellar membrane proteins in the plane of the flagellar membrane. This signaling pathway in vegetative Chlamydomonas reinhardtii appears to involve an influx of calcium, a rise in intraflagellar free calcium concentration and a change in the level of phosphorylation of specific membrane-matrix proteins. It is hypothesized that flagellar surface contact with a solid substrate (during gliding), a polystyrene microsphere or another flagellum (during mating) will all activate a signaling pathway similar to the one artificially activated by the use of monoclonal antibodies to flagellar membrane glycoproteins. A somewhat different signaling pathway, involving a transient rise in intracellular cAMP level, may be associated with the mating of Chlamydomonas gametes, which is initiated by flagellum-flagellum contact. The hypothesis that the widespread observation of microsphere movements on various ciliary and flagellar surfaces may reflect a mechanism normally utilized to transport axonemal and membrane subunits along the internal surface of the organelle membrane presents a paradox in that one would expect this to be a constitutive mechanism, not one necessarily activated by a signaling pathway. PMID- 1305477 TI - A cytoplasmic dynein heavy chain in sea urchin embryos. AB - By making the hypothesis that the pattern of conserved sequence residues in the vicinity of the hydrolytic ATP-binding site of dynein would resemble that in myosins from a broad variety of sources, we designed degenerate oligonucleotide primers capable of amplifying this region of multiple dynein isoforms from sea urchin embryo poly(A)+ RNA. Quantification of the expression of two of these dynein isoforms has shown that the level of mRNA encoding for the beta-heavy chain, like that of tubulin, increases 2-3-fold after deciliation of the embryos, whereas the expression of the second dynein isoform, like that of actin, is essentially unaffected. This second isoform is believed to be the cytoplasmic dynein of sea urchin embryos. PMID- 1305478 TI - Chymotrypsin-like protease activity associated with demembranated sperm of chum salmon. AB - Our previous study suggested that a chymotrypsin-like protease was involved in the motility of chum salmon sperm (Inaba K, Morisawa M, Biomed Res (1991) 12, 435 437). In this study, we examined the peptidase activity of demembranated sperm of chum salmon using ten synthetic peptides. When spermatozoa were treated with 0.04% Triton X-100 for extracting the plasma membrane and the suspension was separated into the Triton-soluble and insoluble fractions by centrifugation, only the hydrolytic activity towards succinyl (Suc)-Leu-Leu-Val-Tyr-4-methylcoumaryl-7 amide (MCA), a typical substrate for chymotrypsin-like protease, was mostly retained in the insoluble fraction. The bulk of the activities toward other substrates was detected in the soluble fraction. Flagellar axonemes isolated from demembranated sperm showed considerable hydrolytic activity toward Suc-Leu-Leu Val-Tyr-MCA and the activity was still retained in the axoneme even after further washing. The hydrolysis was activated by a low concentration of SDS, suggesting that the protease associated with the axonemes is a multicatalytic ATP-dependent proteinase (proteasome). Motility of demembranated sperm was inhibited by Suc-Leu Leu-Val-Tyr-MCA in an ATP-concentration-dependent manner. These results suggest that proteasomes associated with flagellar axoneme regulate flagellar motility. PMID- 1305479 TI - Temperature effect on the ciliary beat frequency of human nasal and tracheal ciliated cells. AB - Even though all human respiratory cilia are similar in structure, they experience a wide range of temperatures between the initial part of the nasal fossae which behave as heat exchangers and the inferior part of the trachea, particularly when we inhale exceedingly cold or hot air. The ciliary beat frequency of ciliated cells from human nasal mucosa and from bronchial mucosa averages 8 Hz when measured at room temperature. In the present study we compared the ciliary beat frequency of human cells from nasal and tracheal mucosa brushings at different temperatures from 5 degrees C to 50 degrees C using two different techniques, ex vivo and in vitro: ex vivo in culture medium less than 24 h after sampling and in vitro after demembranation and reactivation according to a standard procedure developed in our laboratory. Measuring the ATP-reactivated ciliary beat frequency allowed us to check the thermal parameters of the dynein ATPase and all the axonemal machinery. No significant difference in frequency was observed between nasal fossae cilia and tracheal cilia when comparing extreme temperatures in both experimental procedures. PMID- 1305480 TI - Cytoskeletal elements in arthropod sensilla and mammalian photoreceptors. AB - Ciliary receptor cells, typified by cilia or modified cilia, are very common in the animal kingdom. In addition to the cytoskeleton of their ciliary processes these receptors possess other specific prominent cytoskeletal elements. Two representative systems are presented: i) scolopidia, mechanosensitive sensilla of various arthropod species; and ii) photoreceptor cells of the retina of the bovine eye. Two cytoskeletal structures are characteristic for arthropod scolopidia: a scolopale typifies the innermost auxiliary cell, and long ciliary rootlets are extending well into the sensory cells. The latter element is also characteristic for the inner segment of the photoreceptor cells in bovine. The scolopale of scolopidia is mainly composed of actin filaments. In the absence of myosin, the uniform polarity of the actin filaments and their association with tropomyosin all indicate a stabilizing role of the filament bundles within the scolopale. This function and a certain elasticity of actin filament bundles may be important during stimulation of the sensilla. The ciliary rootlets of both systems originate at the basal bodies at the ciliary base of the sensory cells and project proximally. These rootlets are composed of longitudinally oriented, fine filaments forming a characteristic regular cross-striation. An alpha-actinin immunoreactivity was detected within the ciliary rootlets of scolopidia. In addition, antibodies to centrin react with the rootlets of both types of receptors. Since centrin is largely responsible for the contraction of the flagellar rootlets in green algae, contraction may also occur in the ciliary rootlets of insect sensilla and vertebrate photoreceptors. In both systems, contraction or relaxation of the ciliary rootlets could serve in sensory transduction or adaptation. PMID- 1305481 TI - Centrin is a component of the pericentriolar lattice. AB - Here, we use three polyclonal anticentrin antisera designated 08/28, 26/14-1, and 26/14-2 to further characterize the pericentriolar lattice of metazoan cells. All of these antibodies give an indistinguishable localization pattern that consists of a constellation of pericentrosomal spots. In QT6 cells these spots are few in number and closely associated with the centriolar region, whereas in PtK2 cells they are more numerous and distributed further from the point of microtubule focus. In mitotic cells, centrin is localized to the spindle poles and spindle apparatus. We demonstrate here that the pericentriolar lattice of PtK2 and QT6 cells is, in part, composed of proteins characterized by acidic pIs (4.4 to 5.4), low molecular mass (M(r) 18,500-21,000), and calcium-binding; these attributes and the immunoreactivity of these proteins to anticentrin antibodies indicate that they are centrin isoforms of metazoan cells. Finally, we confirm our earlier observation that PtK2 cells contain a centrin-related protein of M(r) 165,000; QT6 cells also contain centrin-related proteins (M(r) 64,000-165,000). We conclude that centrin is a component of the pericentriolar lattice of higher eukaryotic centrosomes. PMID- 1305482 TI - Cells of the BAL fluid in patients with acute and chronic bronchitis (preliminary study). PMID- 1305483 TI - Reversal of the endotoxin-induced bronchial hyperreactivity to histamine by the platelet activating factor antagonist BN 52021. PMID- 1305484 TI - Bacteria in bronchial asthma. PMID- 1305485 TI - Possibilities of immunomodulation in atopic dermatitis: a preliminary trial with broncho-vaxom. PMID- 1305486 TI - Broncho-vaxom in the treatment and prophylaxis of recurrent respiratory tract infections in bronchial asthma. PMID- 1305487 TI - The role of infections in upper respiratory tract allergic diseases. PMID- 1305488 TI - Preliminary clinical assessment of the leukocyte migration inhibition test (LMIT) with cow's milk antigens in the diagnosis of recurrent obturative bronchitis in infants. PMID- 1305489 TI - Simple and inexpensive method to assay IgG antibodies anti pollen. PMID- 1305490 TI - Determination of specific IgG antibodies with an immunofluorescence method (IF) before and after vaccination with Pollinex. PMID- 1305491 TI - An attempt to demonstrate the possibility of depressing delayed reactivity with antibodies: tuberculosis as an experimental model. PMID- 1305492 TI - Bacteria and their products as occupational allergens. PMID- 1305493 TI - An attempt to demonstrate the involvement of genetic factors in allergic inflammatory processes of the airways. PMID- 1305494 TI - Indications for the vaccination of patients with allergic-inflammatory processes of the airways. PMID- 1305495 TI - Treatment with an autovaccine of a patient with catarrhal rhinitis, nasal polips and infectious bronchial asthma. PMID- 1305496 TI - The influence of environmental factors (antibiotics) on workers in the pharmaceutical industry. PMID- 1305497 TI - Flunisolide (Syntaris) and beclomethasone (Beconase) in the treatment of non allergic eosinophilic rhinitis. PMID- 1305498 TI - Long term study of aerosol corticosteroid treatment (Syntaris) in nasal polyps. PMID- 1305499 TI - The coexistence of chronic sinusitis with bronchial asthma. PMID- 1305500 TI - Cellular immunity in infants with congenital sublaryngical hemangioma. PMID- 1305501 TI - Microbiological and cytological analysis of patients with nasal polyps. PMID- 1305502 TI - The interdependence of allergy and infection in an homogeneous population of 478 young males. PMID- 1305503 TI - The participation of aerobic and anaerobic flora in the pathogenesis of inflammations of the lower respiratory tract (preliminary report). PMID- 1305504 TI - Bacteria of the upper and lower respiratory tract in patients with allergic inflammatory diseases. PMID- 1305506 TI - Skin reactivity to staphylococcal strains in a normal subject. PMID- 1305505 TI - Skin tests in the evaluation of pathogenicity of bacterial strains present in allergic-inflammatory processes of the airways. PMID- 1305507 TI - The interpretation of delayed bacterial skin reactivity tests in patients with infectious bronchial asthma, spastic bronchitis and some forms of catarrhal rhinitis. PMID- 1305508 TI - Comparative studies of skin reactivity in health and chronic respiratory infection. PMID- 1305509 TI - Bronchoalveolar cell count and its relationship to bronchial hyperreactivity after antigen challenge in asthmatics. PMID- 1305510 TI - Invasive diagnostic procedures in airway inflammation. PMID- 1305511 TI - Functional efficiency of the auditive tube in children with pollinosis. PMID- 1305512 TI - Wheezy bronchitis in children; etiopathogenetic role of non-infectious agents. PMID- 1305513 TI - The presence of inflammatory cells in the bronchi of patients with allergic inflammatory processes. PMID- 1305514 TI - Granulocyte migration abnormality in patients suffering from allergic rhinitis. PMID- 1305515 TI - Bacterial flora in patients with chronic cor pulmonale during aggravation of symptoms. PMID- 1305516 TI - Analysis of patients with chronic bronchitis hospitalized in the Departments of the Institute of Internal Medicine, Pomeranian Academy of Medicine in Szczecin, from 1983 to 1987. PMID- 1305517 TI - Arginine-vasotocin (AVT)--a pineal hormone in mammals. AB - Covering more than 30 years of studying the pineal peptide hormones physiology, this study largely discusses the main personal research as well as international literature indirectly or directly supporting the idea that the nonapeptide hormone arginine-vasotocin (AVT) is a pineal hormone in mammals. After a short review of the problem, the data are structured in two chapters: one including all the indirect arguments, i.e. those results demonstrating that the ly synthetic exogenous AVT mimics all the effects attributed to the pineal gland itself or to its releasing hormone the indole melatonin, or are contrary to those reported after pinealectomy, and a second chapter that includes all the data directly demonstrating that AVT is contained, synthetized and released from the pineal gland of mammals. Special emphasis was placed on the personal results regarding the AVT effects, the mechanisms of action, the release and interference with some of the basic functions of the brain such as sleep, behaviour, attention or maturation. PMID- 1305518 TI - Therapeutic methods in endocrinology. General considerations. AB - The integrative character of the endocrine system and its regulation ways generate and motivate the specificity of endocrine therapy. The latter tries, by its methods and means, to restore hormonal homeostasis, to imitate the biologic rhythms of secretion, to respond to the stress needs, in fact it ensures the dynamics of the normal integration of an individual in the daily life with all its changes. This requirement is ensured by the methods of stimulation and suppression, hormonal substitution or depression of hormone bio-synthesis, blockade of enzymatic activation or desensitivation of the receptors to the hormonal message, etc. The association of the therapeutic means and methods has the purpose of bringing relief and the expectancy of a decent, controlled survival in inevitable iatrogeny. Endocrine therapy also ensures a normal growth and development, an acceptable IQ, a reasonable degree of sexualization, responds to the most important demand of life: perpetuation of the species. The range of endocrine therapy is perhaps the widest in medicine, starting with the disease and ending with the esthetic aspects of the individual. A good knowledge of the methods, means and especially their dynamics and specificity gives the endocrinologist the pragmatic outlook measured only by its efficiency. PMID- 1305519 TI - The role of free radicals in normal and pathologic cell proliferation. AB - Oxygen, while essential for life, is at the same time involved in the toxic effects of exposure to ionizing radiations, U.V. and a variety of chemical substances. All these cause an increased production of oxygen-derived free radicals (ODFR) and a modified pro-oxidant state. Many studies point to the involvement of the mechanisms controlled by ODFR in regulating the normal cell proliferation. In recent years, much evidence has been gathered implying the ODFR in the mechanisms of initiating and promoting the neoplastic transformations in vivo and in vitro, and in the activation of specific oncogenes. PMID- 1305520 TI - [Machina carnis--editorial comment on the article by Z. Wunsch]. PMID- 1305521 TI - [A textbook presentation of muscle contraction. Contribution by the editor]. PMID- 1305522 TI - [Machina carnis. Will the picture of molecular mechanisms in muscle contraction change?]. PMID- 1305524 TI - The Co-Morbidity of Depression, Anxiety and Substance Abuse among American Indians and Alaska Natives. Proceedings of a workshop. April 8-10, 1991. PMID- 1305523 TI - Comorbidity: meaning and uses in cross-cultural clinical research. AB - American Indians and Alaska Natives were the subject of a workshop sponsored by the National Institute of Mental Health and the Indian Health Service. Comorbidity of anxiety, depression, and substance abuse is highly prevalent in these two populations, and this was the focus of the meeting. This paper introduces the topic of psychiatric comorbidity, and considers the topics of culture, psychiatric diagnosis, and assessment. Future research directions and a brief summary of the papers presented at the workshop, which are included in this issue, are provided. PMID- 1305525 TI - Culture, diagnosis and comorbidity. PMID- 1305527 TI - Co-morbid symptoms of depression and conduct disorder in First Nations children: some findings from the Flower of Two Soils Project. AB - The prominence of co-morbidity in children and adolescents has increased over the past decade as new empirical research data has accumulated. Yet little epidemiological data of any kind exists for First Nations Children. Following a brief literature review on co-morbidity in children and adolescents, the authors analyzed data from the Flower of Two Soils Project (M. Beiser, principal investigator) to examine more closely the relationship between self-reported depressive symptoms and parent/teacher reported conduct symptoms. Such a relationship has been consistently found in a number of studies. Children aged 7 to 10 were found to show more academic and social problems when rated as having high conduct symptoms. Children in the co-morbid group were found to have the highest rates of family stress and help-seeking behavior. Suicidal ideation was as high in the conduct and co-morbid groups as it was in the high depression group. More First Nations children were found in the high conduct-low depression group. The significance of these findings is discussed. PMID- 1305526 TI - "Feeling worthless": an ethnographic investigation of depression and problem drinking at the Flathead reservation. AB - The study of depression, drinking and suicidality has long preoccupied students of American Indian life, in part because of the assumed connection between these specific forms of psychiatric distress and generalized demoralization. Given the significant variation in suicidal behavior and prevalence rates intertribally, this assumption deserves closer attention. Recently, researchers working with Western populations have sought to clarify the relationships among depression, alcohol abuse and suicidality through an explicit investigation of their comorbidity. Using data collected at the Flathead Reservation, this paper explores the degree to which the investigation of the comorbidity of these three disorders can validly reveal the relevant contours of psychopathological distress in a cross-cultural setting. The data show that while the comorbidity of problem drinking and depression can sometimes indicate severe psychopathological distress, measured in this case by suicidality, comorbidity cannot account for another group at high risk for suicide. The discrepancy is explicable with reference to the cultural construction of depression, drinking and suicidality in relation to the creation, maintenance and disruption of social bonds, rather than in relation to an internal state of demoralization. PMID- 1305528 TI - Stressful life events and co-occurring depression, substance abuse and suicidality among American Indian and Alaska Native adolescents. AB - Depression, suicidality and substance abuse disorders are examined with special emphasis on the role of stressful life events in predicting severity and patterns of comorbidity among American Indian and Alaska Native adolescents in boarding school environments. Both amount and severity of comorbidity increase with age and specific patterns of comorbidity are associated with gender. Different types and amounts of stressful life events predict specific combinations of comorbidity. These outcomes are interpretable with respect to associated cultural dynamics and the ecology of mental health services delivery for Indian and Native adolescents. Theoretical and methodological issues are discussed in relation to the use of stressful life events in examining cultural factors related to comorbidity among culturally different populations. PMID- 1305529 TI - Use of the CES-D in an American Indian village. AB - In this paper, we examine the performance of a pencil-and-paper screening questionnaire on depressive symptoms (the Center for Epidemiologic Studies Depression Scale, or CES-D) in a sample of 120 adult American Indians belonging to a single Northwest Coast tribe. Results of factor analyses suggest that somatic complaints and emotional distress are not well differentiated from each other in this population. CES-D scores (which have shown good sensitivity and specificity for depressive disorders in this sample) also show weak and apparently nonsignificant trends to be elevated in the presence of other psychiatric diagnoses (including alcoholism) or general impairment. However, because of the use of a convenience sample (rather than a probability sample), analyses of associations between study factors--including comorbidity--are liable to produce spurious results due to selection bias (including Berkson bias). On this basis, we suggest that the use of probability samples should assume a high priority in cross-cultural studies. The study of the entire population of interest is another solution to the sampling problem, particularly in small communities. PMID- 1305531 TI - Alcoholism and substance abuse among selected southern Cheyenne Indians. AB - This family and small community-based study reports the occurrence of alcoholism and co-occurring substance abuse in Southern Cheyenne Indians living in western Oklahoma. Sociocultural factors complicate operationalization of clinical data into standard (DSM-III-R) psychiatric disorder terminology; understanding sociocultural factors is essential for assessing the high rate of addictive disorders in this group. To obtain reliable and valid clinical diagnoses, data from several sources were utilized within a blind rating system: 1) SADS-L, a clinician-administered research diagnostic instrument; 2) MAST; 3) relatives; 4) medical records; 5) other official documents. The sample consisted of 69 males (45 alcoholics) and 97 females (36 alcoholics). Among clinically significant substance abusers (moderate impairment of function), 22 of 24 were alcoholics. In non-alcoholics, mean MAST scores were 8.8 (males) and 5.1 (females); in alcoholics, 32.0 (males) and 38.7 (females). Mean age of onset on heavy use of alcohol was 20.1 yrs. (males) and 22.8 (females) (p = 0.047); among all alcoholics, 86% (males) and 64% (females) had early onset (< 25 yrs. old). When data from 98 unrelated subjects were analyzed separately, similar findings were observed except that mean age of onset of heavy use of alcohol was more discrepant between males and females, viz. 20.1 versus 22.8 yrs. (p = 0.02). Among those with substance abuse disorders, early age of onset was present in all but one female. In these Cheyenne, alcoholism is usually clinically severe and early in onset; it often co-occurs with substance abuse, also early in onset. PMID- 1305530 TI - Substance use and other psychiatric disorders among 100 American Indian patients. AB - One hundred American Indian patients with a Psychoactive Substance Use Disorder (PSUD) were studied with special reference to associated psychiatric disorders. This clinical sample was divided into three groups: PSUD only, PSUD plus an Organic Mental Disorder (OMD), and PSUD plus any other psychiatric disorder. OMD diagnoses included primarily Delirium Tremens and Alcoholic Hallucinosis; cases of Alcohol Amnestic Disorder, Alcohol Dementia, and trauma-induced OMD were also encountered. Other psychiatric disorders included primarily Major Depression and Anxiety Disorder, with smaller numbers of Schizophrenia, Conduct, Sexual, and other Disorders. Demographic and clinical characteristics were compared among these three groups. Those with PSUD+OMD tended to be older, male, and have more DSM-III Axis 3 disorders (American Psychiatric Association 1980) as compared to other patients; those with PSUD+other diagnoses tended to be single and younger. Education and occupational status were not related to the three diagnostic groups. The data were also subjected to MANOVA analysis. Even when corrected for sex, types of substance being abused, Axis 3 health status, and other factors, the three diagnostic groups still bore a significant relationship to age. Those with PSUD+Other psychiatric diagnoses besides OMD tended to be youngest. Those with PSUD-only were intermediate by age, while those with PSUD+OMD tended to be the oldest. PMID- 1305532 TI - The natural history of medical and psychiatric disorders in an American Indian community. AB - In 1969, a Pacific Northwest American Indian community cohort (n = 100) was interviewed for the presence of physical and psychiatric illnesses. The same community was studied again in 1988. This study describes the outcome among the original 100 subjects. The schedule for Affective Disorders and Schizophrenia Lifetime Version (SADS-L) served as the basic interview instrument, supplemented by data from medical records, death certificates, and medical and community informants. Twenty-five subjects had died, 13 from cardiovascular disorders and seven from alcohol-related illnesses. Among the 46 subjects re-interviewed, hypertension, heart disease, and diabetes had become significant sources of medical morbidity. Alcoholism was the most significant cause of psychiatric morbidity, particularly among males. This study indicates that greater attention should be focused upon prevention and treatment of alcoholism, cardiovascular disorders, and diabetes in this community and in other American Indian populations. PMID- 1305534 TI - [Evaluation methods of memory in depression]. AB - The aim of this review is the description of the main modifications of memory of depressive subjects. Cognitive alterations concerning long term and working memory, results of tests dealing with learning items or stories with affective contents. Capacities of depressed subjects on the word completion test (implicit memory) are preserved. In a second part these cognitive particularities will be reviewed in integrative models and these theoretical approaches and their limits will be discussed. Finally, as a general conclusion, difficulties encountered in neuropsychological investigations of depressive subjects will be stressed. PMID- 1305535 TI - [Exploration of memory disorders in anxiety states]. AB - According to cognitive model of anxiety, memory process in anxious patients is usually tested by comparing the incidental recall of positive and negative, threatening and non threatening, self and other-referenced words. Contrary to expectation, the results indicate relatively poorer memory for threatening material in anxious patients and no bias in favour of the recall of self referent negative words. At the opposite this memory bias can be evidenced in patients with panic disorder. The bias for anxiety words is better evidenced in the subgroups with the higher arousal level or when there is a mood induction by reading first an anxiogenic text. Consistent with prediction a perceptive pre attentional bias can be shown for the great majority of the subjects studied in recent researches. PMID- 1305533 TI - Treatment implications of comorbid psychopathology in American Indians and Alaska Natives. AB - This paper discusses treatment implications of comorbid psychopathology in the context of American Indian and Alaska Native culture and in the context of the Indian Health Service's Mental Health and Alcohol and Substance Abuse Program Branches. Treatment of comorbidity in this population is a particularly difficult problem due to numerous barriers to treatment and a poorly defined treatment system. As in other clinical populations, these patients are high utilizers of the limited treatment services available, but may not receive the type of treatment they need. After describing the extent of comorbidity in this population, we present an historical perspective of mental illness that provides an Indian's view of why we are where we are today in treating these problems. Next, we discuss Western and traditional treatment implications for comorbidity among adults and adolescents. Finally, we suggest directions for future research in this area. PMID- 1305536 TI - [Occupational hygiene of railway transport workers as a specific branch of occupational medicine]. AB - Occupational hygiene of the railway transport is a well defined sphere of knowledge. It is closely connected with the general occupational medicine and yet occupies a significant place in the railway medicine. Occupational medicine of the railway transport is based on results of sciences connected with each other and at the same time it serves for the favourable research is included sciences, such as occupational physiology and hygiene pathology, sanitary technics, chemistry, acoustics et al. PMID- 1305537 TI - [Necessity of individual approach to evaluating the level of fatigue during prolonged work in the mountains]. AB - Capacity to the physical work and functional status were studied during the prolonged (1 year) work in the mountainous conditions (3,600 m above sea level). The fatigue grade and capacity level were proved to depend on individual adaptation to the mountainous conditions. PMID- 1305539 TI - [Review of the journal "Polish Journal of Occupational Medicine" through 1988]. PMID- 1305540 TI - [Review of the "American Journal of Industrial Medicine",1989,vol.15, no.2,4]. PMID- 1305538 TI - [Utilization of individual protective devices with autonomic air supply for work with hazardous materials ]. AB - An application of individual protective means (IPM) with the autonomic air supply has considerable promise for protecting respiratory organs and eyes in hazardous conditions. The main advantage of such devices is that the respiratory zone has the forced supply with the cleansed air. Biophysical studies showed that such IPM don't harm the functional status and capacity for work in human doing the medium difficult physical work during 8 hours and can be recommended for the application in mines. PMID- 1305541 TI - [Cobalt and alcohol cardiomyopathies (Clinical aspects, differential diagnosis,pathogenesis)]. PMID- 1305542 TI - [Evaluation of the workload in the various modes of tractor driving]. AB - Two modes of tractor driving--by means of unstepped and frictional turn mechanisms--were compared. The study revealed the advantage of unstepped turn mechanism according to changes of the body functional status. PMID- 1305543 TI - [Medical consequences of drinking water pollution resulting from a chemical accident]. AB - The article describes consequences of the chemical accident in Ufa, lead to the drinkable water pollution by phenol and chlorophenolic compounds. Events required the prompt prophylactic measures and reconstruction of health care in the city. The treatment tactics approved at that period of time are represented. PMID- 1305544 TI - [Actual problems of allergy in occupational pathology]. AB - Data from different sources concerning the modern status of the allergy problem in the occupational pathology are represented. Features of immunologic pathogenesis in occupational respiratory tract diseases formation due to the simple and composite substances, protein denaturants, immune modulators and histamine-liberators organic and non-organic by origin are described. The most promising directions for the further investigation of the problem are stated and based. PMID- 1305545 TI - [Photometric detection of metacide in the air of the working area]. AB - The method of photometric detection of metacide in the air is based on the interaction of latter with p-nitrophenyldiasonium in borate-buffer solution. The measurement takes place in 10 mm-basins at the wave-length 540 nm. The lower limit of detection is 0.15 mg/mm when 167 L of air are analysed. PMID- 1305546 TI - [Rapid method of calculating the heat resistance of clothes using programmable microcomputers]. AB - Microcomputer calculation of the heat resistance of clothes gives the current data for the wide range of air speed. Programme is based on the equation, summarizing the number of standard clothing layers. Other methods (using of dummies, trials on humans) were analysed and the results identical to the suggested method were obtained. PMID- 1305547 TI - [Gas chromatographic detection of 2- chlorbutadiene- 1,3 and 2,3-dichlorbutadiene 1,3 in skin wash-off]. AB - Highly sensitive, selective method of 2-chlorobutadiene-1,3 and 2,3 dichlorobutadiene-1,3 detection by means of gas chromatography in the skin wash off is worked out. The sensitivity is 0.2 microgram for 2-chlorobutadiene-1,3 and 1 microgram for the 2,3-dichlorobutadiene-1,3. PMID- 1305548 TI - [MAC of hazardous substances in the air of the working area, set by the USSR Ministry of Health in 1991]. PMID- 1305549 TI - [Workload evaluation in technicians responsible for maintenance of medical radiographic equipment]. PMID- 1305550 TI - [Study of mercury ionic sorption from the gastrointestinal tract]. PMID- 1305551 TI - [Information on basics of MAC for m-toluate iodide in the air of work area]. PMID- 1305553 TI - [Modern hygienic norm setting for occupational poisons in the air of the working area]. AB - The peculiarity of modern hygienic norm setting is the application of rapid methods of MAC basement in the air of working area. Criteria of rapid norm setting for occupational poisons are summarized, the extent of further investigations and expedience of norm setting for chemical substances in the air of working area are defined. PMID- 1305552 TI - [Status of the vestibular analyzer and psychophysiologic parameters in miners and crew members cleaning up the consequences of the Chernobyl nuclear plant accident]. AB - Status of the vestibular analyzer and psychophysiologic parameters were studied in 20 miners with the long length of service and in 16 liquidators of Chernobyl atomic power station accident consequences. Liquidators showed the reliably increased latent periods of P1, N1 and P2 spikes of vestibular evoked potentials, considerably increased latent time of the complicated oculomotor reaction and lowered rate of information processing. Exposure to increased radiation dose during the work at Chernobyl atomic power station was a main factor to influence on the functional status of vestibular analyzer. PMID- 1305554 TI - [Occupational hygiene and health status in welders of laser devices]. AB - Welders-assemblers of the Quant-type laser devices are exposed to bright light flashes of plasma and laser exceeding in certain measurements the maximal allowed level. Such hazards induce disorders in eyes, autonomic nervous, circulatory and immune systems of workers. Impaired humoral immunity can lead to increased incidence of acute respiratory tract diseases. Prophylactic measures, including laser and flash shielding screens and drug therapy were suggested. PMID- 1305555 TI - [Program for promotion of breast feeding in Poland. I. Justification of the program with supporting information]. AB - A breast-feeding promotion programme for Poland was developed as a part of governmental programme to protect and improve health of the mother, child and family for the years 1986-2000 carried out by Institute of Mother and Child. It was presented as a document consisting of three major components which will go to press successively. Part I covers justification of the proposed programme activities and thirty five consistent paragraphs summarizing principal information on breast-feeding and its promotion. PMID- 1305556 TI - [Concentration of erythropoietin in blood serum of the umbilical cord and in amniotic fluid in normal and complicated pregnancies]. AB - Erythropoietin is the primary hormone controlling erythropoiesis in both adults and fetuses. In extra-fetal life the main organ producing erythropoietin is the kidney which is responsible for producing about 90% of the total amount of this hormone. In fetal life erythropoietin is produced by the liver of the fetus. The erythropoietin production depends on the content of oxygen in blood. This is probably the only physiological stimulus which regulates the production of erythropoietin. The increase of erythropoietin concentration in the umbilical cord serum and in the amniotic fluid has been observed in the states of fetus anoxia. This mainly concerns such complications during pregnancy as the fetus hypotrophy, diabetes, serological conflict, and gestosis. PMID- 1305557 TI - [Diagnostic value of directed anamnesis and gynecologic examination with regard to HSG investigation in diagnosis of mechanical infertility in women]. AB - The aim of the work has been hysterosalpingographic estimation of oviductal patency in women with case histories encumbered or not encumbered by inflammations restricting the fertility, with taking into consideration the anatomical state of the reproductive organs being evaluated by gynaecological examination. Of 429 women covered by the study 102 out of a group of 277 with primary infertility reported adnexitis in their case histories, while 67 women out of a group of 152 with secondary infertility declared having had inflammations. In women, whose anamnesis included inflammations, uterine adnexa thickening as well as abdominal position of uterus with restricted movements appeared in the group of examined women with primary infertility (15.2%) about twofold, and in the group with secondary infertility (26.5%) over fourfold more frequently than in women with inflammatory--free case histories. The women, in whom the gynaecological examinations failed to reveal any changes in genital organs, regardless of the fact that they reported adnexitis, were found to have uni- or bilateral in patency of oviducts from 43.7% to 96.2%, mean in 53.74%, and in those with pubescent uteri on the average 53.75%, with thickened uterine adnexa--mean 64.46% with abdominal position and restricted movements of uterus on the average 74%. Oviductal in patency was recorded twofold more frequently in women, whose case histories disclosed uterine adnexitis. PMID- 1305558 TI - [Evaluation of combined application of diazepam, fenoterol and metamizole in prevention of uterine-tubal spasm during the performance of hysterosalpingography]. AB - In the years from 1989 to 1991 HSG examination was carried out in 502 infertile women. Two hours before the examination 5 mg of diazepam and 5 mg of fenoterol were orally administered, and 30 minutes prior to the procedure 2.5 mg of metamizole were given intramuscularly. The examined population of women was found to have normal patency of oviducts in 412 (82.07%) women, 48 (9.56%) had uni- or bilateral impatency of abdominal openings, in 16 (3.19%) there was uni- and in 19 (3.78%) bilateral +impatency of oviducts in uterine segments, while in 7 (1.39%) alternating impatency was disclosed. Of 502 women in 109 patients laparoscopy and chromotubation were performed during a period from 2 to 16 months after HSG examinations. In 30 (93.7%) out of 32 women with impatency of oviducts in the proximal segment, the diagnosis was confirmed. The administered drugs effectively prevent uterine-tubal spasms occurring at the time HSG is being accomplished. PMID- 1305559 TI - [Developmental anomalies of the uterus in a population of 3000 women with various causes of infertility]. AB - In the years from 1979 to 1991 a population of 3000 women with various causes of infertility was found to have in 13.34% developmental anomalies of uteri. As many as 9.27% consisted of saddle uteri, 2.67% bicornous, in 0.37% there was partial, and in 0.13% complete septum, in 0.57% unicornous and in 0.33% double. The diagnosis of developmental anomalies involving uterus was based mainly on HSG, laparoscopic and hysteroscopic examinations. PMID- 1305560 TI - [Effect of hydrotubation on the anatomical state of oviducts in women with mechanical infertility]. AB - The aim of the paper was to evaluate the anatomical state of uterine adnexa in women operated on due to mechanical infertility. Hydrotubation were previously applied in 31 women stemming from various centres in the country, while in 31 such a treatment was not performed at all. The mentioned groups of women were encumbered, to a similar degree, with a risk factor of infertility, except for the duration of sterility, which in those treated by hydrotubation lasted on the average 2 years longer. From 5 to 50 hydrotubations were carried out, most frequently in series of 5 procedures. It was reported by the women that 8 of them after hydrotubation experienced hypogastric pain persisting for some days, and in 6 there was acute adnexitis. Destructive changes in uterine adnexa, being estimated during the reconstructive operation, were decidedly more advanced in women treated by hydrotubation. That was expressed mainly by frequent appearance of lytic adhesions as well as by more advanced fibrosis of oviducts, particularly that of endosalpinx. Unchanged oviducts, after their release from adhesions, also appeared less frequently. PMID- 1305561 TI - [The value of ultrasound examination for diagnosing postmenopausal metrorrhagia]. AB - The results of transvaginal ultrasound diagnostic assessment of endometrium were compared with histopathological examination of endometrium by following diagnostic abrasion on examined group of 54 postmenopausal women. The method seems to be useful for diagnosis of postmenopausal metrorrhagia, when the "safe" thickness of endometrium layer is taken as 5 mm. It occurs in effect of our study the transvaginal ultrasound examination may decrease the number of subsequent diagnostic abrasions in those cases. PMID- 1305563 TI - [Ultrasound diagnosis of vesico-uterine fistula]. AB - The case of vesico-uterine fistula after cesarean section was described. Ultrasound technique was used to confirm the diagnosis because of noncharacteristic urography and absence of typical changes in urine analysis. Surgical intervention with good result was performed 3 month after cesarean section. PMID- 1305562 TI - [Evaluation of an immunoenzymatic assay for determining estrogen and progesterone receptors in breast tumors]. AB - The aim of our research was the usability of immunoenzymatic assay for the determination of estrogen and progesterone receptors. We tested 59 women with breast tumours. 20 of these women have had carcinoma ductal, 10 carcinoma lobular and 3 women another histopathological type. 26 women have had benign tumours: 15 mastopathia fibrosocystica, 11 fibroadenoma. It was found that mean concentration of cER, nER and cPgR, nPgR were higher in malignant tumours as compared with benign tumours. Mean concentration of cER in carcinoma ductale (mean = 45.96 fmol/mg protein) and carcinoma lobular (mean = 130.38 fmol/mg protein) were of higher statistical significance than the levels of these receptors in mastopathia fibroso-cystica (mean = 16.82 fmol/mg protein). Mean concentrations nER and nPgR in benign and malignant tumours were not statistically significant. On the basis of our own investigations we can suggest that immunoenzymatic method supplied by Abbott is a simple test to perform and useful to evaluate hormonal dependence of cancer tissue. PMID- 1305564 TI - [Treatment of ureter injuries after obstetric-gynecologic surgery]. AB - The article presents an analysis of 21 patients with ureter injuries originated during obstetric-gynaecological operations treated in Urology Clinic in Medical Academy Poznan. Attention was particularly focused on prevention and fast diagnosis of injuries based on intra-operation examination usg, urography, and ascending pyelography. This fast diagnosis is of crucial importance for the cure. PMID- 1305565 TI - [Giant cyst of the spermatic vesicle imitating abdominal tumor]. AB - A paper presents the case of big cystic degeneration of spermatic vesicle found accidentally. Diagnosis was established on the basis of the objective examination and the following additional examination: urography, computer tomography, cystoscopic examination and rectal examination. The radical excision was performed and as a result full cure was achieved. PMID- 1305567 TI - [Endoscopy in gynecology and obstetrics]. PMID- 1305568 TI - [Diagnostic laparoscopy in the gynecology clinic at the academy of medicine in Bialystok during the years 1989-91]. AB - The authors present the results of 1056 diagnostic laparoscopies carried out from 1989 to 1991 in the Clinic of Gynecology of Medical School in Bialystok. Sterility was the leading indication for diagnostic laparoscopies in 92.7% of patients. Suspicion of ectopic pregnancy was the reason of 44 laparoscopies. 46.5% of diagnosed infertile women had adhesions in pelvis post inflammation or surgery. 10.6% of them had massive pelvic adhesions and the tubes were damaged without any chance for surgical correction. The endometriosis was found in 15% of infertile women, and 17% of patients had no pelvic pathology. PMID- 1305566 TI - [Involuntary ureteral micturition]. AB - The paper focuses on the problem of ureteric incontinence of urine caused by dislocation of bladder ureteral orifice. A case of a 15-year old patient suffering from incontinence of urine, admitted to the Urological Clinic has been described. In order to avoid vaginoscopy, the following examinations were performed: urography, chromocystoscopy, arteriography and computer tomography. The reason for such a large number of various examinations was an unclear picture of the left kidney and the shape of the ureter, suggesting a tumour in the retroperitoneal space. The treatment ended with a removal of the kidney. The disclosed retroperitoneal space turned out to be affected by hydronephrosis. PMID- 1305569 TI - [Ambulatory laparoscopy as an alternative to hospitalization]. AB - Laparoscopy is a new way of activity in gynecological diagnostics and therapy, but it is still hardly acceptable in our country. It is caused by long-lasting habits of performing traditional and more invasive treatment. One of directions in development of gynecological diagnostics is performing laparoscopy in out patient conditions, or in conditions close to hospital in out-patients units. Our study shows the range of indications to performing this kind of procedures. Possible late complications after laparoscopy are described, which in author's opinion should not be a contraindication to performing these procedures. PMID- 1305570 TI - [Laparoscopy in the gynecologic clinic]. AB - Three thousand and twelve (3012) diagnostic laparoscopies in children, girls and women were carried out during the period 1970--1992. The age of the patients was between 6--49 years. The present studies show that laparoscopy fills up the space between the clinical investigation and laparotomy probatoria. It helps to solve in a clear way, a lot of diagnostic problems in gynecology in adult women, in gynecology of developmental age and gynecological endocrinology. There were the following indications to laparoscopy: 1. Adnexitis chronica 2. Infertility primary and secondary. 3. Unclear tumor and pelvic infections in adolescence. 4. Primary and secondary failure of ovaries. 5. Suspicion of polycystic ovaries. 6. Second look laparoscopy. 7. Suspicion of endometriosis. 8. Suspicion of ectopic pregnancy. 9. Developmental faults of sexual organs. 10. Pubertas praecox. PMID- 1305572 TI - [Pelvic endoscopy in diagnosing fallopian tube disorders that cause infertility]. AB - Over the period of 25 years, 1080 pelvic endoscopy in infertile women were performed, with special attention payed to the pathology of Fallopian tubes. Pelvic endoscopy was performed after previous HSG. During the pelvic endoscopy, the state of the uterus, ovaries and uterine tubes were evaluated, with much attention paid to the condition of the abdominal ostium of the uterine tube, symptoms of active and chronic inflammation, endometriosis, the authors also tried to diagnose the extension and character of pelvic-salpingian adhesions. Confrontation of the results enabled diagnosis in 111 (41.7%) women, out of 266, with patient Fallopian tubes the organic factors which impaired conception or made conception impossible. In the group of 814 women with tubal impotency in 15 (1.8%) cases extratubal factor was found, subserosal myoma in uterine horn, cyst, adhesions, while Fallopian tube itself was patent and unchanged. Organic factors of Fallopian tube disorder were determined. In 360 (44.2%) patients, out of 814, with tubal impotency pathological status was found (active salpingitis, tuberculosis, endometriosis) which required establishing of a necessary treatment and cancelling the surgical treatment. PMID- 1305571 TI - [Role of pelvic endoscopy in diagnosing congenital uterine malformations]. AB - The role of pelvic endoscopy in diagnosing uterine abnormalities, considering material of 1170 patients, is presented in this paper. It has been documented that pelviscopy together with hysterosalpingography play basic role in determining type of uterine abnormality. In 20 cases pelvic endoscopy enabled verification of the primary diagnosis set by hysterosalpingography. Pelvic endoscopy is a method by choice in the diagnostics of the Rokitansky-Kuster Hauser syndrome. PMID- 1305573 TI - [Laparoscopy in diagnosing and treating endometriosis]. AB - Clinical study in 98 women with genital endometriosis was performed. In 33 patient endometriosis was treated by operative laparoscopy-electrocauterization of foci in 20 women, ovarian cyst resection in 9 and cyst extrication in 4. In 10 cases laparoscopy was followed by laparotomy. Very high correlation between endometriosis and infertility was found (71.4%). Very few patients conceived till now (28.57%). Searching in the time of laparoscopy very subtle foci of endometriosis was stressed. PMID- 1305574 TI - [Laparoscopy in diagnosis and treatment of polycystic ovaries]. AB - Value of the laparoscopy in diagnostic process and treatment of the polycystic ovaries was analysed. Authors have presented changes in the procedure which occurred after developing new technologies. The first results of the operative laparoscopy, with use of monopolar cauterization are described. PMID- 1305575 TI - [Laparoscopy followed by laparotomy]. AB - Authors have presented 45 clinical situations where laparoscopy was followed by laparotomy. Pre- and intraoperative diagnosis was analyzed. Dense adhesions were the most common indication to perform laparotomy (43%). PMID- 1305577 TI - [Laparoscopy in the diagnosis of chronic painful disorders of the pelvis]. AB - The objective of the paper was the evaluation of the results in laparoscopic examinations performed in women reporting chronic painful ailments in the pelvis. The investigation has covered 194 women in whom the laparoscopic procedure was performed by multidirectional diagnostic examinations, and the inflammatory changes had been excluded. The most frequent change recorded during laparoscopy was adhesions of the pelvic organs 103 (53.09%). In 58.63% of cases the cause of adhesions were post inflammatory states of uterine adnexa, in 24.8% the post operative procedures, in 9.2% the adhesions accompanied endometriosis, while in 7.22% the adhesions were the cause responsible for the retroflexion of uterus. In 29.38% the studied group of women was found to have a normal image of the pelvis, and in 8.76% there was a picture of congested pelvis. Laparoscopy is a valuable diagnostic examination, frequently allowing to establish the cause of chronic painful ailments in the area of pelvis, therein also some forms of functional disturbances. PMID- 1305576 TI - [Nineteen years of laparoscopy in the gynecology clinic IPG PAM]. AB - The aim of the paper was the analysis of 1450 laparoscopic procedures performed in the Clinic of Gynecology--IOG PMA in Szczecin in the years from 1974 to 1992. The above number include 320 laparoscopic operations. In the analyzed three five year periods, the number of laparoscopies increased twofold, while in the years 1989-1992 it constituted 26.8% of all the operative procedures. Indication for laparoscopy in 74.6% of cases was sterility, in 13.38% pelvic pain of undefined etiology, in 7.7% ectopic pregnancy, 1.8% oncologic indications, in 0.5% internal ones, in 0.3% sterilization and others in 1.6%. Among operative laparoscopies electrocoagulation of endometriosis was carried out in 46.6% of cases, resection of intraperitoneal adhesions in 27.5%, in the region of abdominal orifices of oviducts in 7.5%, ectopic pregnancy operations in 7.2%, excision of ovarian cysts in 6.6% as well as extirpation of myomas in 4.7%. At the analyzed period the following complications were disclosed, namely: interstitial lesion in 2 cases, hemorrhage from inferior epigastric artery in 1 and subcutaneous emphysema in 34 cases. PMID- 1305578 TI - [Results of treating endometriosis with infertility using operative laparoscopy]. AB - In the work, the efficiency of treating endometriosis by hormonal as well as combined methods, and employing the operative laparoscopy was evaluated. The study involved 89 infertile women with endometriosis being of various grade of advancement. Sixty women underwent combined treatment according to Samm, the remaining 29 were given hormonal therapy with Danazol and Orgametril preparations. After combined treatment full recovery was obtained in 26.7% of cases, improvement in 40%, but after the use of preparations Orgametril, Organon or Danazol, Winthrop, complete cure was reached in 12.8% of cases, improvement in 31%. Only 8 women became pregnant after combined therapy. Complete recovery concerned mainly less advanced endometriosis, particularly following the combined treatment according to Semm. Early laparoscopic diagnosis increases the chance of curing endometriosis and fertility associated with it. PMID- 1305579 TI - [Use of laparoscopy in gynecology]. AB - Paper concerns 1822 performed laparoscopies. The most frequent indications to laparoscopy were: sterility, adnexal mass, tubal pregnancy and pelvic pain syndrome. In 80% cases of sterility we found pathologic findings, which could be the cause of sterility. adnexal mass, tubal pregnancy and pelvic pain syndrome. In 80% cases of sterility we found pathologic findings, which could be the cause of sterility. In 75% of cases we confirmed adnexal mass, which were operated by laparoscopy or by laparotomy. In 17 cases we confirmed unruptured tubal pregnancy, which were conservatively operated by laparoscopy or by laparotomy. Laparoscopy is useful method in gynecology, especially in diagnostically difficult cases of gynecologic disease. PMID- 1305580 TI - [Laparoscopic surgery in gynecologic practice]. AB - Paper concerns 293 laparoscopic operations. The most frequent types of laparoscopic operations in presented material were: adhesion lysis in minor pelvis (33.8% cases), cystectomy and cyst-ovariectomy (27.6%) and electrocoagulation of ovarian capsule. Operative laparoscopy because of small injury is useful method in the treatment some gynecological disease. PMID- 1305581 TI - [Complications of endoscopy in gynecology]. AB - The paper concerns the complications which appeared during 1822 laparoscopies and 141 hysteroscopies. The overall percentage of complications in presented material was 0.82% for laparoscopy and 2.8% for hysteroscopy. The most frequent complication during performance of laparoscopy was subcutaneous emphysema (8 cases). The most frequent complication during hysteroscopy was uterine wall perforation, which appeared in 3 cases during incision of dense and massive intrauterine adhesions. All patients with complications of gynecologic endoscopy recovered well. PMID- 1305582 TI - [Use of diagnostic and operative hysteroscopy in clinical practice]. AB - In the paper authors present indications and results of 141 hysteroscopies. The most frequent indications were: sterility, Asherman syndrome suspected, infertility and abnormal uterine bleeding. 55 diagnostic and 86 operative hysteroscopies were performed. In sterility and infertility group of patients were present 49.6% pathological findings of uterine cavity, between them the most frequent were: uterine septa and intrauterine adhesions. In the remaining cases the intrauterine pathology were present in 75.8% cases, between of them the most frequent were intrauterine adhesions and endometrial hyperplasia. Hysteroscopy should be the method of choice in some cases of gynecological pathology. PMID- 1305583 TI - [Diagnosis and treatment of uterine changes effecting fertility using hysteroscopy]. AB - The aim of this study was evaluation of uterine factors in sterility and infertility using hysterosalpingographic and hysteroscopic techniques. Sixty five women ranged in age from 22 to 40 years were included in this study. The results of performed hysterosalpingographies and hysteroscopies were compared. Intrauterine changes found during diagnostic procedures were removed in operative hysteroscopy and the effectiveness of this treatment was estimated by pregnancy rate. The most frequent changes found within cervical canal and uterine cavity were adhesions and endometrial polyps. The rate of uterine septa and submucous myomas were considerable lower. Hysteroscopy was found the best diagnostic method in evaluation of intrauterine conditions for fertility and considerably increased the range of information about the type and location of uterine abnormalities. The removal of those changes during operative hysteroscopy increased the fertility rate in women treated with this procedure. PMID- 1305584 TI - [Usefulness of hysteroscopy in diagnosing sterility]. AB - Sterility is a severe social problem. Using hysteroscopy, which is possible thanks to development of medical technology, seems to be an important improvement in diagnostics and therapy of sterility. The aim of this study is evaluation of the usefulness of hysteroscopy in diagnostics of sterility. There was a group of 106 women with diagnosed primary sterility and 82 women with secondary sterility. Wolf and Storz hysteroscopes were used during examinations, whereas the uterine cavity was dilated by CO2 using Wolf Metrometer 2121. During this examination a normal uterine cavity was found in most cases (32.9%). The next findings were: endometrial polyps (27.6%), intrauterine adhesions (23.4%), sub-serous myomas (14.3%), and congenital uterine abnormalities (1.5%). Comparing outcomes of hysteroscopy in both groups of sterile women, the high rate of intrauterine adhesions in the secondary sterility (43.9%) was detected. Performing hysteroscopy in patients with sterility increases considerably the range of informations about reproductive organs. Also the possibility of eye-controlled biopsy, deliberation of intrauterine adhesions or removing of endometrial polyps during endoscopic procedure increases the value of hysteroscopy. PMID- 1305585 TI - [Evaluating the possibility of performing diagnostic and operative hysteroscopy depending on the type of hysteroscopy and agent used for filling the uterine cavity]. AB - The aim of the paper is to present own experiences concerning diagnostic and operative hysteroscopy performed with 4 types of hysteroscopes. Flexible hysteroscope HYP 1T, rigid hysteroscope 5 mm in diameter with single flow, operative hysteroscope 8 mm in diameter with constant flow, hysteroresectoscope 9 mm in diameter with constant flow produced by Olympus; for filling the uterine cavity CO2 0.2% NaCl, 5% glucose, Purisol, Hyskon were implemented. In even case the degree of hardship of the procedure, traumatism for the patient, degree of operated-on patient's safety during the procedure, possibility of applied in the presence of bleeding, price of instrument and agents applied for filling the uterine cavity were estimated. It has been found out that the use of rigid hysteroscope 5 mm in diameter and operative hysteroscope 8 mm in diameter with constant flow and utilization of CO2 as well as Purisol and Hyskon solutions provide possibility of extensive diagnosis and therapy. PMID- 1305587 TI - [Vaginal delivery after previous cesarean section]. AB - Data concerning frequency of cesarean section as well as frequency of vaginal delivery after cesarean section in Poznan region in years 1990-1991 were presented. During last years we observed significant increase of spontaneous deliveries after cesarean section. The indications for the previous cesarean section and the outcome of the present pregnancy are discussed. PMID- 1305586 TI - [Diagnosis of fetal hemolytic disease and therapeutic possibilities]. AB - The possibility of fetal blood sampling and direct blood transfusion into fetal circulation began the new direction in diagnostics and treatment of fetal haemolytic disease. Early diagnostics and possibilities of intrauterine treatment of the fetus enabled effective treatment also in severe hydrops cases. In the article diagnostic and therapeutic scheme introduced in the I Department of Obstetrics and Gynaecology and Central Rh-disease Unit in Warsaw was presented. PMID- 1305588 TI - [Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits]. AB - The aim of this study was to evaluate the influence of female sex hormones on phenazone pharmacokinetics using as an experimental model female rabbits after a bilateral ovariectomy. Eighteen female rabbits divided into two groups: control animals and experimental rabbits, that underwent ovariectomy, were used in the study. Pharmacokinetic assays were performed in all animals: prior to the study, after 1 month and after 2 months. Blood was sampled within 24 hours after intragastric administration of phenazone at a dose 50 mg/kg b.w. Two compartment open model was used for calculations. Significant increase in AUC and prolongation of phenazone halflife as well as a decrease in the total body clearance were noted. The study demonstrated the possible inhibition of the microsomal mixed-function oxidase system by oestrogens. PMID- 1305589 TI - [Sinusoidal and pseudo-sinusoidal patterns in cardiotocography--differentiation and prognosis]. AB - Examples of cardiotocograms looks like a graph of a sine function were presented. The differentiation of these various patterns was discussed. The most usefull parameters were amplitude and frequency of long-term variability and its relation to the uterine contractions and short-term variability. PMID- 1305590 TI - [The course of pregnancy with placenta praevia diagnosed in the 2nd and 3rd trimester]. AB - Selected clinical features of the course of pregnancy in 118 gravidas with placenta praevia diagnosed ultrasonographically on the first breeding were compared. The clinical features significantly connected with bleeding and the prognostic features for the way of delivery were stated. The longest bleeding was observed in patients with partial or marginal placenta praevia. The most common anterior location of low placenta praevia was connected with the lowest risk as regards the cesarean section due to hemorrhage. The earlier occurrence of the bleeding was associated with its longer duration. The time of the occurrence of the first bleeding and its duration were associated with a duration of the pregnancy and a body mass of the newborn. The recurrence of bleeding was of no prognostic importance. The appearance of the first bleeding after the 28th week of pregnancy was significantly connected with the necessity of performing a cesarean section due to hemorrhage in case of central, partial or marginal placenta praevia. In case of low-lying placenta the way on delivery was significantly related to the time of appearance of the first bleeding and the distance between the placenta and the internal os. Fisher's linear discriminative function of the two features allowed for the determination of a mathematical formula for the prognosis of the way of delivery in case of a low-lying placenta. PMID- 1305591 TI - [Comparison of mammography and sonography in diagnosis of breast cysts]. AB - Mammography and sonography were done in 479 women. In mammography cysts were suspected in 10 cases, in 20 cases solid lumps and in 49 cases no changes were detected. In sonography in 7 cases cysts were found in 23 solid lumps, in 49 no changes were detected. It was proved that sonography is much more accurate in detecting cysts than mammography. PMID- 1305592 TI - [Thyroid carcinoma from material of the surgery department at the oncology clinic, Medical Academy in Poznan]. AB - From among 612 cases of various kinds of thyroid diseases operated in the Surgical Department of the Oncological Clinic, we present here 24 cases (3.92%) of thyroid carcinoma. They are divided according to sex, staged to TNM system and histopathologic diagnosis. Discussed were the range of performed operations which depended on the results of histopathologic examinations. They were compared with the current principles of thyroid carcinoma treatment. Owing to the significance of inter-operational examination, in order to establish the range of the operation, the authors suggest that necessity of surgical treatment in cases of thyroid carcinoma, in centers which have at their disposal a histopathological laboratory. PMID- 1305593 TI - [Role of gynecology in etiopathogenesis of cervical carcinoma]. AB - Cancer as a natural stochastic phenomenon and disease can be promoted by many non specific factors, including also such gynecological ones as: 1. faulty prediction and determination of birth date: 2. instrumental instead of possible natural labor; 3. reduction rather prolongation of lactation; 4. acceptation of early sexual life; 5. wrong hormonal therapy; 6. longlasting prescription of pills; 7. infrequent diagnosis and wrong therapy of hypothalamic conditioned abortions and premature deliveries; 8. clinical, colposcopic and cytologic false negative diagnosis of cervical cancer; 9. eradication of neoplastic lesion without normalization of environment, and 10, too radical and aggressive treatment of precancerous states. Medicine as no other field of human activity requires from the gynecologists the specific responsibility for conscientious constant acquisition of general knowledge to ensure the future of human species especially in conquering "cancer of mothers" and preventing "cancer of early sexual life". PMID- 1305594 TI - [Treatment of tubal pregnancy laparoscopically]. AB - Five cases of unruptured tubal pregnancy treated laparoscopically are described. Basing on the clinical evaluation of them we concluded, that selected cases of unruptured tubal pregnancy may be successfully treated using the laparoscopic technics. The use of this technics is less traumatic for patient, shorted the time of her stay in the hospital and lower the costs of therapy. PMID- 1305595 TI - [Subpopulations of t lymphocytes and lymphocyte proliferative activity in normal pregnancy]. AB - T lymphocyte subpopulations (CD3+, CD4+, CD8+) and the lymphocyte proliferative responses to mitogens (PHA, Con A, PWM), in the environment of fetal calf serum (FCS) were examined in 16 normal primigravidas in the third trimester of pregnancy and in 15 healthy nonpregnant women. In normal pregnant women significantly lower absolute and percentage numbers of CD3+ and CD4+ T cells and almost twice reduced CD4+/CD8+ ratio were found, in comparison with nonpregnant subjects. Despite the shifts among particular T lymphocyte subsets in the peripheral blood, non disorders were found in the lymphocyte proliferative responses to mitogens in normal pregnancy. PMID- 1305597 TI - [Evaluating the usefulness of qualitative analysis of latex c-reactive protein for diagnosing neonatal sepsis]. AB - We analyzed the results of determinations C-reactive protein (Latex Test Dialab firm) of 136 newborns. We divided them into three groups: with generalized infections, with infection without sepsis and without infection. Sensitivity of method for neonates with septicaemia was 60%, for neonates with infection without sepsis--81.25%, together for all infections--66.1%. After overlooking sepsis caused by Staphylococcus epidermidis sensitivity for sepsis was 81.8% and for all infections--81.6%. PMID- 1305596 TI - [Immunomodulating properties of sera in normal pregnant women]. AB - The purpose of this study was to analyze the immunosuppressive properties of sera of normal pregnant women. Effects of pregnancy sera on the proliferation of mitogen (PHA, Con A, PWM)-induced lymphocytes were examined in healthy primiparas. The sera of normal pregnant women inhibited the proliferation of PHA- and Con A- induced both autologous and allogenic lymphocytes (obtained from nonpregnant and pre-eclamptic women), while remaining neutral towards the proliferation of PWM- induced lymphocytes in comparison with fetal calf serum. The basic immunomodulatory activity of the sera in pregnant women was contained in the heat-stable fraction. PMID- 1305598 TI - [Method of delivery and obstetric records of premature labour in material from the Polish Mother's Health Center Memorial Hospital]. AB - 526 premature labours between the 28th and the 36th week of pregnancy were recorded at the Polish Mother's Health Centre Memorial Hospital during the period between April 1989 to September 1991. The mortality rates of newborns were analysed in the group of vaginal and abdominal delivery in the following pregnancy stages: the 28th--the 31st week, the 32nd--the 34th week, the 35th--the 36th week. 23 pregnant delivered abdominally by rapid indications were excluded from the study. In this group cesarean section was caused by placental complications or severe gestosis. This group, as a group of a high obstetric risk, was directly incomparable with vaginal delivery group, that of a low obstetric risk. Newborns with congenital malformations were also excluded from the study. Our analysis allows to assume that cesarean section, when applied in the premature labour between the 32nd and the 34th week of pregnancy, gives much better chances for newborn's survival than vaginal delivery. PMID- 1305599 TI - [Monitoring hormones during the menstrual cycle among sterile women. I]. AB - This paper attempts to estimate the endocrinological function of the following glands: pituitary, thyroid, adrenal, pancreas, and ovary. An examination only once of their hormones was made between the 8th and 10th day of the follicular phase of the menstrual cycle. This examination was performed on 22 sterile women with monophasic menstrual cycle, 119 sterile women with biphasic menstrual cycle and 17 women who delivered at least one child without previous treatment (control group). Radioimmunoassays (RIA) of 11 hormones: LH, FSH, PRL, estradiol, progesterone, cortisol, aldosterone, insulin, T3, T4, and testosterone were made. It was confirmed that the marked differences showed only the examinations of LH and estradiol among sterile women with monophasic menstrual cycle in comparison to the group of sterile women with biphasic cycle and the control group. RIA of the concentrations of the thyroid, pancreas and adrenal hormones among women without endocrinopathy have not a mark diagnostical value. RIA of the level of the testosterone is not appropriate in clinical cases which do not carry symptoms a hyperandrogenism. PMID- 1305600 TI - [Hormonal monitoring during the menstrual cycle among sterile women. II]. AB - This paper attempts to assess the value of the dynamical examinations of the concentrations of the pituitary gonadotropin LH, FSH, PRL in the menstrual cycle. RIA were made on 22 sterile women with monophasic cycle and 119 sterile women with biphasic cycle in comparison with 17 women who delivered at least one child without previous treatment (control group). The dynamical RIA were made on all women between the 5th and the 26th day of the menstrual cycle. The results of these assays were compared in the 8th, 14th, 15th, 16th, 21st and 25th day of the menstrual cycle. It was confirmed that the lower levels of PRL are maintained through all the time of the menstrual cycle among sterile women with monophasic cycle. It is shown that higher level of LH is maintained through all the time of the menstrual cycle but it is particularly higher in the secretary phase of the cycle among sterile women with monophasic cycle. A lower level of FSH was observed at the beginning of the follicular phase of the cycle and a markedly higher concentration of FSH was found on the secretary phase of the cycle among sterile women with monophasic cycle. PMID- 1305601 TI - [Hormonal monitoring of the menstrual cycle among sterile women. III]. AB - This paper attempts to assess the value of the dynamical examinations of the concentrations of the ovary hormones progesterone and estradiol in the menstrual cycle. RIA were made on 22 sterile women with the monophasic cycle and 119 sterile women with the biphasic cycle in comparison with 17 women who delivered at least one child without previous treatment (control group). The dynamical RIA were made on all women between the 5th and 26th day of the menstrual cycle. The results of these assays were compared on the 8th, 14th, 15th, 16th, 21st and 25th day of the menstrual cycle. The examinations confirmed a markedly lower concentrations of estradiol throughout all the time of the cycle among sterile women with the monophasic cycle and a little higher concentrations among sterile women with the biphasic cycle. Markedly lower concentrations of progesterone were observed throughout all the time of the cycle among sterile women with the monophasic cycle and a little higher concentrations of it were found among sterile women with the biphasic menstrual cycle. PMID- 1305602 TI - [Malignant melanoma coexisting with pregnancy]. AB - An extremely rare case of melanoma amelanoticum coexisting with pregnancy has been discussed. Pregnant A. Ch., age 42, was admitted to the Polish Mother's Health Centre Memorial Hospital on the 22nd of August, 1990 with a diagnosis of the 5th pregnancy, the 2nd delivery, the 30th week of gestation, state after cesarean section. Suspected malignant melanoma. Stomach ulceration. Thrombophlebitis of left lower extremity. General condition--medium hard. For the last three days she did not report fetal movements, fetal heartbeat was not detected either. Us examination confirmed fetal death. On the 24th of August, 1990, spontaneous vaginal delivery terminated the pregnancy, giving a dead, macerated female fetus, body weight of 1500 g. On the 3rd day after delivery the patient died with growing circulation-respiratory insufficiency. Autopsy revealed melanoma malignum amelanoticum disseminatum. Neither an autopsy of the fetus nor histopathological examinations of the secundines were performed for the advanced maceration. The coexistence of pregnancy with malignant melanoma in this case brought a tragic end both for the mother and the fetus. PMID- 1305603 TI - Lateralization of the grasp reflex in male and female human newborns. AB - The lateralization of the grasp reflex was studied in male and female newborns. The mean grasp-reflex strength of the right hand was found to be higher than that of the left hand in males, but the difference was not significant. The mean grasp reflex strength of the right hand was found to be significantly higher than that of the left hand in females. There was no significant difference between the mean grasp-reflex strengths of the right hand in the male and female subjects. The mean reflex strength of the left hand was found to be higher in males than females; the difference was only marginally significant. The right minus left (R L) reflex strength showed a significant positive linear relation to the right and left-reflex strengths in both sexes. This was, however, much more pronounced for the right-reflex than the left-reflex. There was a significantly positive linear correlation between the reflex strengths of the right and left hands and the body weight in males. The females did not show such a relationship between reflex strength and body weight. These sex-related differences in the grasp reflex in newborns were discussed in light of cerebral lateralization and its hormonal modulation. PMID- 1305604 TI - The relationships between the degree of grasp-reflex asymmetry, grasp-reflex strength from the right and left hands, and body weight in the male and female newborn with and without familial sinistrality. AB - The relation of the degree of grasp-reflex asymmetry to the strength of right- and left-hand grasp-reflex strength and body weight was studied in human newborn. In the total sample (N = 103), the right minus left (R-L) reflex strength was found to be positively linearly related to the grasp-reflex strengths from the right and left hands in FS-subjects; the correlation was higher for the right hand than the left hand. In FS+ subjects (N = 17), there was not a significant correlation between R-L and right-reflex strength; left-reflex strength was found to be negatively linearly related to the R-L reflex strength. In FS- subjects, the right- and left-reflex strengths showed a positive linear correlation with body weight. In FS+ subjects, only the left-reflex showed a positive linear correlation with body weight. The R-L reflex tended to be positively correlated with body weight in FS- subjects and negatively correlated in FS+ subjects. In females (N = 58), the relation of R-L to right and left reflex was similar to that for the total sample. There was no significant correlation between grasp reflex and body weight in FS- females. In FS+ females (N = 8), there was a positive linear correlation between the right grasp-reflex and body weight; the left grasp-reflex did not show such a significant correlation. The R-L grasp reflex strength was not correlated with body weight in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305605 TI - Changes in psychopathological symptoms in sleep apnea patients after treatment with nasal continuous positive airway pressure. AB - To evaluate the psychological disturbances associated with obstructive sleep apnea (OSA) and the effect of nasal continuous positive airway pressure (NCPAP) treatment on these alterations, personality patterns and psychosocial adjustment were assessed in patients hypnopolygraphically diagnosed with OSA before and after different periods of NCPAP therapy. Prior to treatment, MMPI results for 23 patients showed significant elevations (p < .01) on five clinical scales compared to those of 17 normal controls. Apneics' personality patterns were predominantly of a "neurotic-mixed" type, indicating an anxiety reaction with paranoid features. Depression, schizophrenia, and hypochondriasis were the highest scales. Most patients had severe psychosocial maladjustment. In the follow-up study during the NCPAP treatment, there was a progressive reduction of the psychopathological signs along with a generalized improvement in psychosocial adaptation. These changes were remarkably significant after about a year's treatment, in particular for depression (p < .01) and total adjustment degree (p < .01). It was concluded that severe OSA is associated with serious psychosocial alterations that improve gradually with NCPAP. PMID- 1305606 TI - Right-, left-dominance and ambidexterity in grasp reflex in human newborn: importance of left brain in cerebral lateralization. AB - The grasp reflex was studied in human newborn without familial sinistrality. Of 60 females, 26 (43.3%) were right-handed and 34 (56.7%) ambidextrous. Of 62 males, 20 (32.3%) were right-handed, 39 (62.9%) ambidextrous, and 3 (4.8%) left handed. There was a nonsignificant preponderance of right-dominance in females and a significant preponderance of nonright-handedness in males. In right handers, the mean right minus left (R-L) grasp-reflex showed a positive linear correlation with the grasp-reflex from the right and left hands, with a higher correlation for the right hand. In ambidexters, the R-L grasp reflex did not show any significant correlation with the grasp reflex from the right and left hands. The mean grasp-reflex from right and left were found to be significantly smaller in ambidextrous males and females then right-handed males and females, with a much higher significance for the right hand. It was concluded that females tended to have a more pronounced reflex lateralization than males. The results also indicated that the left brain may be more important than the right brain for the development of a spinocerebral motor lateralization in humans. PMID- 1305607 TI - Anoxic encephalopathy: a case study of an eight-year-old male with no residual cognitive deficits. AB - Anoxia is generally associated with impaired learning, memory, attention, and planning. We present a case of near-drowning (5-15 minute anoxia) with subsequent 15 hour coma that is extremely unique because of (1) the absence of neuropsychological and neurological deficits 3 1/2 months post-injury, and (2) the availability of pre-injury intelligence testing for comparison. Findings are important as previous research has suggested residual deficits will be evident after much briefer coma. The present findings suggest anoxic encephalopathy does not automatically result in neurological or cognitive impairment. PMID- 1305608 TI - Is postmenopausal osteoporosis related to pineal gland functions? AB - There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis. PMID- 1305609 TI - The pineal gland and spontaneous abortions: implications for therapy with melatonin and magnetic field. AB - Spontaneous abortion, the termination of pregnancy prior to 20 weeks of gestation, is estimated to occur in 40%-50% of all pregnancies and in 12%-15% of identified pregnancies. The causes of spontaneous abortion can be divided into two main categories: those arising from chromosomal anomalies and those arising from abnormalities in the intrauterine environment. In the following communication, we propose that deficient pineal melatonin functions in early pregnancy may be causally related to the development of spontaneous abortions in cases where chromosomal anomalies or structural abnormalities of the uterus have been excluded. This hypothesis is based on the findings that: (a) melatonin plasma levels normally increase by 200%-300% in the first 20 weeks of pregnancy; (b) melatonin decreases uterine contractility in the rat; (c) melatonin stimulates the secretion of progesterone, which decreases uterine contractility and prevents immunological rejection of the trophoblast; (d) melatonin inhibits the synthesis of prostaglandins, which are potent inducers of uterine contractility and labor, and (e) pinealectomy increases the number of spontaneous abortions in pregnant rats. In addition, since melatonin is a hormone with immunosuppressant properties, we propose that the increased melatonin production in early pregnancy may contribute to a state of "transplantation immunity" to the paternal histocompatibility antigens preventing immunological rejection of the trophoblast. If this hypothesis is correct, then plasma melatonin, levels during early pregnancy could be used as an indicator for increased risk of spontaneous abortions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305610 TI - Seasonal panic disorder: a possible variant of seasonal affective disorder. AB - The present communication concerns a 30 year-old female patient with panic disorder in whom panic attacks appeared to be seasonally-related. Characteristically, attacks were more frequent and severe during the months of October to May with spontaneous remissions during the months of June to September. Since 70% of patients with seasonal affective disorder (SAD), a variant of affective illness characterized by recurrent winter depressions with remissions in summer, suffer from anxiety disorders, we propose that seasonal panic disorder may be a variant of SAD. Since SAD is associated with phase delay of circadian rhythms, some forms of panic disorder may be related to phase instability of circadian rhythms. Moreover, since administration of artificial bright light therapy is currently the most effective treatment for SAD, it is suggested that patients with panic disorder should be questioned as to whether their symptoms are seasonally related. If a positive association is established, these patients should be offered treatment with light therapy prior to or coincident with the institution of pharmacotherapy. PMID- 1305611 TI - Dystonia as the presenting manifestation of multiple sclerosis. PMID- 1305612 TI - The inhibitory effect of the muscarinic agonist pilocarpine on lymphocyte activation involves the IL-2 pathway and the increase in suppressor cell function. AB - The inhibition of lymphocyte DNA synthesis by the cholinergic muscarinic agonist pilocarpine (5 x 10(-4) M) was not reversed by addition of exogenous recombinant Interleukin-2 (100-1000 IU/ml). Pilocarpine did not inhibit Interleukin-2 (IL-2) production by human peripheral blood mononuclear cells but decreased the number of interleukin-2 receptor bearing cells (TAC positive cells). Furthermore, pilocarpine increased the CD8:CD4 T lymphocyte ratio enhancing the suppressor cell function. All these effects were blocked by the muscarinic antagonist atropine (1 x 10(-6) M). As described for the specific lymphocyte nicotinic stimulation, the pure cholinergic muscarinic stimulation inhibits lymphocyte proliferation by enhancing suppressor activity. PMID- 1305614 TI - "Positive" and "negative" movement disorders in schizophrenia. AB - Investigations aimed at identifying the clinical characteristics that discriminate tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. We have suggested, based on pharmacological and neuroradiological studies, that TD in schizophrenia may be a covariate of positive symptoms while drug-induced parkinsonism (DIP) may relate to negative symptoms. To investigate this hypothesis, we examined in 47 institutionalized schizophrenic patients the relationship of TD and DIP with psychopathology clusters rated on the Positive and Negative Syndrome Scale. We found that involuntary movements of TD were significantly associated with the activation cluster (p < .01), whereas DIP was significantly associated with the anergia cluster (p < .01). These findings thus support the position that TD is a specific facet of the positive syndrome in schizophrenia, while DIP is a specific feature of the negative syndrome. Clinically, the data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for TD, while those with prominent negative features could be at increased risk for DIP. In analogy with the positive/negative dichotomy, we propose that TD could be regarded as a "positive," while DIP as a "negative" movement disorder. PMID- 1305613 TI - Fc gamma receptors are expressed on human neuroblastoma cell lines: lack of correlation with N-myc oncogene activity. AB - FcRs (Fc Receptors) have been detected on the cell surface of two human neuroblastoma cell lines; IMR 32 and SK-N-SH, by immunocytochemistry and flow cytometric analysis, using a previously characterized polyclonal antiserum raised against the Fc gamma R isolated from a human CLL line (Gorini, Medgyesi, Garavini, Dorrington and Down, 1987; Rozsnay, Sarmay, Szabo, Medgyesi, Gorini and Gergely, 1990). FcR is expressed on all the cells of both lines at least at the same level as on the HL60 promyelocyte cell line used as positive control. Two electrophoretic components displaying apparent molecular masses of 70 and 43 kDa respectively have been identified by SDS-PAGE followed by Western blotting analysis of crude cell membranes. In addition, "in situ" hybridization experiments seem to exclude a correlation between FcR expression and N-myc oncogene activity. The presence of FcR in neuroblastoma could be related to a possible functional role even on these cells which do not belong to the immune system; moreover, they could also be exploited for a diagnostic characterization of this tumor. PMID- 1305615 TI - Pattern of CBF in the rehabilitation of visuospatial neglect. AB - The CBF was assessed in seven patients before and after rehabilitation for visuospatial neglect. Two months of treatment produced an increased perfusion both in the right posterior and left anterior areas of the brain. However, only the left anterior CBF increase was correlated with the neglect disorders. The left anterior improvement in CBF was inversely correlated with right-left cerebellum asymmetry in pre- and post-treatment. The present data suggest the role of the frontal eye-fields in the mechanism of recovery of visual exploration in patients with severe neglect. PMID- 1305616 TI - Similarities between sylvian fissure asymmetries in cat brain and planum temporale asymmetries in human brain. AB - Galaburda et al. (1987) have suggested that asymmetry of planum temporale in men would result from an asymmetrical neuronal loss; symmetry would implicate a failure of asymmetrical cell loss. There are several reports indicating a similarity between men and animal in cerebral lateralization. In the present work, a morphological analysis was performed in sylvian fissure (SF) of cats. Asymmetry coefficients (AC) were distributed symmetrically and normally with a mean of zero. However, female cats exhibited a relatively stronger leftward asymmetry (left SF > right SF), and male cats a relatively stronger rightward asymmetry in SF. The results generally supported those of Galaburda and his coworkers. Deviations from their results depended mainly on paw preference. The similarity between human brain and animal brain was accentuated once more concerning cerebral lateralization. The results were not appropriate to conclude about the mechanisms of cerebral lateralization. Testosterone in males and estrogen in females were suggested to be the main hormones contributing to the emergence of cerebral lateralization. PMID- 1305617 TI - Associations among right minus left brain weight, right- and left-brain weight and the degree of paw preference in right- and left-preferent male and female cats. AB - The relation of right and left brain weight to right minus left (R-L) brain weight and the relation of R-L paw use to brain weight were studied in adults cats. The R-L brain weight was significantly larger than zero in right-pawed (RH) male and left-pawed (LH) females. The R-L brain weight was significantly smaller than zero in LH males, not significantly different from zero in RH females. The R L brain weight was negatively linearly correlated with the left-brain weight in RH and LH males (no significant correlations in females). The R-L paw use showed a significant positive linear correlation with the R-L brain weight in RH male and females. There was a significant negative linear correlation between R-L paw use and R-L brain weight especially in LH males. Total brain weight showed a significant negative linear correlation with R-L paw use in RH males, and a positive linear correlation in LH males (no correlations in female cats). These results indicated that intermanual difference in paw use is associated with interhemispheric weight difference and total brain weight, especially in male cats; the left brain seems to be of importance in cerebral lateralization. PMID- 1305618 TI - Lateral orientation, eye movements and dichotic listening. AB - Past studies have found that lateral orientation (eye or head turn) may influence hemispheric asymmetry on the dichotic listening task. The present work studied the effects of forced head and eye turn on a consonant-vowel dichotic test. Spontaneous conjugate lateral eye movements (CLEM) in response to questions were also measured. The subjects were 29 male and 25 female right-handed university students. The dichotic test was administered using a forced-attention method rather than free recall in order to control for attentional bias. As predicted, right lookers on the CLEM test, showed an enhanced right ear advantage while left lookers showed a diminished right ear advantage. This suggests that characteristic hemispheric arousal may enhance or inhibit asymmetry on perceptual laterality tests. No relationship was found between dichotic listening and forced head or eye turning. It was noted that past experiments may have failed to control for the attentional bias introduced by having the head or eyes turned to one direction. PMID- 1305619 TI - Hemispheric priming: effect of response mode on a position replication task. AB - Ten male and ten female dextral subjects performed a kinesthetic position replication task under two response mode conditions; in one block, subjects indicated their decision by a lateralized verbal response and in the other block, by a midline chin-lift response. Response mode was found to interact with arm, excursion length, end position, and sex. This interaction is interpreted to reflect the influence of verbal preparation on the relative balance between a left hemisphere-biased strategy of kinesthetic positioning and a right hemisphere biased strategy involving a spatial reference system. PMID- 1305621 TI - Successful treatment of multiple sclerosis with magnetic fields. AB - The present communication concerns a 50 year-old woman with a 15 year history of chronic-progressive multiple sclerosis (MS) in whom extracranial application of picoTesla magnetic fields (MF) produced a dramatic and sustained improvement in disability. In contrast, administration of melatonin (3 mg, P.O.) produced in this patient a rapid exacerbation of disability which was reversed subsequently by treatment with MF. It is hypothesized that the therapeutic effects of picoTesla MF involve the mediation of the pineal gland which is known to act as a magnetosensor. The report demonstrates, for the first time, the remarkable efficacy of weak MF in the symptomatic treatment of chronic-progressive MS and underscores the pivotal role of the pineal gland in the pathophysiology of MS. If confirmed by a larger cohort of patients, extracranial application of picoTesla MF may prove as an extremely efficacious, nonpharmacological modality for the treatment of MS. PMID- 1305620 TI - Magnetic fields in the therapy of parkinsonism. AB - In a recent Editorial published in this Journal, I presented a new and revolutionary method for the treatment of Parkinson's disease (PD). I reported that extracranial treatment with picoTesla magnetic fields (MF) is a highly effective, safe, and revolutionary modality in the symptomatic management of PD. My conclusion was based on experience gained following the successful treatment of over 20 Parkinsonian patients, two of whom had levodopa-induced dyskinesias. None of the patients developed side effects during a several month period of follow-up. In the present communication, I present two reports. The first concerns four Parkinsonian patients in whom picoTesla MF produced a remarkable and sustained improvement in disability. Three of the patients had idiopathic PD and the fourth patient developed a Parkinsonian syndrome following an anoxic episode. In all patients, treatment with MF was applied as an adjunct to antiParkinsonian medication. The improvement noted in these patients attests to the efficacy of picoTesla MF as an additional, noninvasive modality in the therapy of the disease. The second report concerns two demented Parkinsonian patients in whom treatment with picoTesla MF rapidly reversed visuospatial impairment as demonstrated by the Clock Drawing Test. These findings demonstrate, for the first time, the efficacy of these MF in the amelioration of cognitive deficits in Parkinson's disease. Since Alzheimer's pathology frequently coexists with the dementia of Parkinsonism, these observations underscore the potential efficacy of picoTesla MF in the treatment of dementias of various etiologies. PMID- 1305622 TI - Parenchymal "damage" in transient ischemic attacks (TIAs) and prolonged reversible ischemic neurologic deficits (PRINDs):--the role of cranial CT and EEG. AB - Over a period of 6 years (1985-1990) we reviewed records of patients with one or more TIAs or PRINDs (196 TIAs, 63 PRINDs). 111 patients (42.9%) suffered from TIAs/PRINDs of the anterior circulation. In all cranial CT scanning (CCT) was performed, whereas only in 79 EEG was recorded after recovery from the symptoms. 25 patients (22.5%) out of the 111 showed low density areas of recent onset in CCT made responsible for the attack. Among the EEGs of the 79 patients 35 (44.3%) revealed corresponding electrical abnormalities. Out of the 79 patients investigated by both methods in 14 (17.7%) a lesion was demonstrated in CCT and focal abnormality in EEG. In 11 (13.9%) EEG was normal despite a lesion manifested in CCT. Vice versa 21 patients (26.6%) showed normal CCTs but focal abnormalities in EEG. By far most cases (43%) had normal CCTs and EEGs. These results may contribute to a redefinition of TIA and PRIND as clinically defined syndromes in prae-CT-area. PMID- 1305623 TI - Low-dimensional chaos in event-related brain potentials. AB - The quantification of a chaotic system, such as the nervous system, can be made by calculating the correlation dimension (D2) from a sample of the data it generates. The encephalogram was recorded from the vertex during an auditory "odd ball" paradigm and was signal-averaged to reveal the event-related potentials (ERPs). A new method for continuously estimating D2, the "Point-D2" (PD2), was determined from the same data, and it also was signal-averaged. The PD2 method was found to be more accurate than others currently used for investigating finite data; it also was found to track nonstationarities that arise within the data. A significant (p < .001) PD2-decrease accompanied the ERPs evoked by target stimuli; the PD2 onset-latency and peak did not correlate with any ERPs. The very short latency suggests that the PD2-decrease may be associated with "selective stimulus set," an interpretation that has been related to early cortical ERP components. PMID- 1305624 TI - Age-related changes in attended and unattended P3 latency in normal subjects. AB - Event-related potentials to visual attended and unattended stimuli were studied in 37 normal subjects between the ages of 19 and 91. The components of the P3 responses to rare nontarget stimuli and rare target stimuli were measured as P3a and P3b, respectively. Both the P3a and P3b latencies were significantly and positively correlated with age. The N2 finding of age-related latency prolongation was comparable to the P3a changes with age. From the standpoint of the theory of automatic and controlled processing, these results suggest that both automatic processing, as reflected by the P3a, and attentional controlled processing, as reflected by the P3b, are impaired with normal aging. PMID- 1305625 TI - Pineal calcification in relation to menopause in schizophrenia. AB - I have suggested that critical changes in melatonin secretion, as mediated by the pineal gland, may exert a crucial role in the onset and pathogenesis of schizophrenia. Since pineal calcification (PC) is thought to reflect the metabolic and secretory activity of the gland, I investigated in 29 randomly selected chronic institutionalized female schizophrenic patients the association of PC on CT scan with premenopausal (prior to age 40) versus menopausal (ages 40 55) onset of illness. The premenopausal patients were found to show a significantly higher prevalence of PC than the menopausal patients (55.5% vs. 18.1%; X2 = 3.93, df = 1, p < .05). Since PC was unrelated to historical, demographic, and treatment variables, these findings highlight the importance of the pineal gland for the timing of the onset of schizophrenia, particularly in relation to the female reproductive state. The results carry theoretical implications on the pathogenesis of schizophrenia and suggest that the pineal gland may exert a protective effect against its onset. PMID- 1305626 TI - Influence of education on WCST performances in schizophrenic patients. AB - Schizophrenic patients have been widely reported to fail in performing Wisconsin Card Sorting Test (WCST). These data have been mostly interpreted as cognitive difficulties and/or neurofunctional impairment inherent to schizophrenia. Nevertheless, checking sample characteristics, the importance of variables as education appears relevant. In our study we examined schizophrenic patients and controls with low and high educational levels respectively. ANOVA results show significant differences on WCST performances for the variable diagnosis (schizophrenics and controls) and for the variable educational level (low and high educational level). It therefore seems necessary call for caution in interpreting WCST results in schizophrenic patients when educational level is not considered. PMID- 1305628 TI - Inverse correlation between right-paw use and body weight in right-pawed male cats and left-pawed female cats. AB - The association between paw preference and body weight was studied in cats. In right-pawed males, the right minus left (R-L) paw use significantly decreased as the body weight increased. There was no significant correlation between these parameters in left-pawed males as well as in right-pawed females. In left-pawed females, the frequency of the left-paw use increased as the body weight increased. These results partly supported those in humans (Tan, in press). It was suggested that hormonal factors affecting body weight may also influence cerebral lateralization and consequently paw preference. The best possibility for these hormones appears to be testosterone. PMID- 1305627 TI - Electroacupuncture accelerated the expression of c-fos protooncogene in serotonergic neurons of nucleus raphe dorsalis. AB - It has been proposed that the FOS protein encoded by c-fos protooncogene functions as a nuclear "third messenger" molecule that couples short-term extracellular signals to long-term alterations in cell function, by regulating the expression of specific target genes. In the present study, immunocytochemical double staining technique was used to investigate the effects of electroacupuncture on the expression of c-fos oncogene in the serotonergic neurons in the nucleus raphe dorsalis (NRD) that has been known to play an important role in the endogenous analgesic system of the brain. The number of FOS positive serotonergic cells in the NRD increased significantly after the electroacupuncture stimulation. These results indicate that electroacupuncture can activate central serotonergic neurons at gene expression level. PMID- 1305629 TI - Effect of weak magnetic fields on biological systems. PMID- 1305630 TI - L-tryptophan in neuropsychiatric disorders: a review. AB - Animal data indicate that serotonin (5-HT) is a major neurotransmitter involved in the control of numerous central nervous system functions including mood, aggression, pain, anxiety, sleep, memory, eating behavior, addictive behavior, temperature control, endocrine regulation, and motor behavior. Moreover, there is evidence that abnormalities of 5-HT functions are related to the pathophysiology of diverse neurological conditions including Parkinson's disease, tardive dyskinesia, akathisia, dystonia, Huntington's disease, familial tremor, restless legs syndrome, myoclonus, Gilles de la Tourette's syndrome, multiple sclerosis, sleep disorders, and dementia. The psychiatric disorders of schizophrenia, mania, depression, aggressive and self-injurious behavior, obsessive compulsive disorder, seasonal affective disorder, substance abuse, hypersexuality, anxiety disorders, bulimia, childhood hyperactivity, and behavioral disorders in geriatric patients have been linked to impaired central 5-HT functions. Tryptophan, the natural amino acid precursor in 5-HT biosynthesis, increases 5-HT synthesis in the brain and, therefore, may stimulate 5-HT release and function. Since it is a natural constituent of the diet, tryptophan should have low toxicity and produce few side effects. Based on these advantages, dietary tryptophan supplementation has been used in the management of neuropsychiatric disorders with variable success. This review summarizes current clinical use of tryptophan supplementation in neuropsychiatric disorders. PMID- 1305631 TI - The influence of the pineal gland on migraine and cluster headaches and effects of treatment with picoTesla magnetic fields. AB - For over half a century the generally accepted views on the pathogenesis of migraine were based on the theories of Harold Wolff implicating changes in cerebral vascular tone in the development of migraine. Recent studies, which are based on Leao's concept of spreading depression, favor primary neuronal injury with secondary involvement of the cerebral circulation. In contrast to migraine, the pathogenesis of cluster headache (CH) remains entirely elusive. Both migraine and CH are cyclical disorders which are characterised by spontaneous exacerbations and remissions, seasonal variability of symptoms, and a relationship to a variety of environmental trigger factors. CH in particular has a strong circadian and seasonal regularity. It is now well established that the pineal gland is an adaptive organ which maintains and regulates cerebral homeostasis by "fine tuning" biological rhythms through the mediation of melatonin. Since migraine and CH reflect abnormal adaptive responses to environmental influences resulting in heightened neurovascular reactivity, I propose that the pineal gland is a critical mediator in their pathogenesis. This novel hypothesis provides a framework for future research and development of new therapeutic modalities for these chronic headache syndromes. The successful treatment of a patient with an acute migraine attack with external magnetic fields, which acutely inhibit melatonin secretion in animals and humans, attests to the importance of the pineal gland in the pathogenesis of migraine headache. PMID- 1305632 TI - Nocturnal plasma melatonin and alpha-melanocyte stimulating hormone levels during exacerbation of multiple sclerosis. AB - The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS). To investigate this hypothesis further, we studied nocturnal plasma melatonin levels and the presence or absence of pineal calcification (PC) on CT scan in a cohort of 25 patients (5 men, 20 women; mean age: 41.1 years; SD = 11.1; range: 27-72) who were admitted to a hospital Neurology service for exacerbation of symptoms. Plasma alpha-melanocyte stimulating hormone (alpha-MSH) estimations were included in the study since there is evidence for a feedback inhibition between alpha-MSH and melatonin secretion. Abnormal melatonin levels were found in 13 patients (52.0%), 11 of whom had nocturnal levels which were below the daytime values (i.e., < 25 pg/ml). Although melatonin levels were unrelated to the patient's age and sex, there was a positive correlation with age of onset of symptoms (p < .0001) and an inverse correlation with the duration of illness (p < .05). PC was noted in 24 of 25 patients (96%) underscoring the pathogenetic relationship between MS and the pineal gland. Alpha-MSH levels were undetectable in 15 patients (60.0%), low in two patients (8.0%), normal in seven patients (28.0%), and elevated in one patient (4.0%). Collectively, abnormal alpha-MSH levels were found in over 70% of patients. These findings support the hypothesis that MS may be associated with pineal failure and suggest, furthermore, that alterations in the secretion of alpha-MSH also occur during exacerbation of symptoms. The relevance of these findings to the pathogenesis of MS are discussed. PMID- 1305633 TI - Auditory brainstem response (ABR) latency: relative importance of age, sex and sensorineural hearing-loss using a mathematical model of the audiogram. AB - Influences of age, sex and audiogram on ABR latencies have been studied. Using a mathematical model of audiogram, the analysis of data finds a relative importance of age, sex and audiogram similar to previous studies. Audiogram slope was correlated only with the latencies of waves I and V, and multiple regression analyses indicate the slope effect is relatively weak compared to that of the other parameters. Using a mathematical model of audiogram did not improve the ABR variance across subjects, underscoring the need to discover other relevant variables to explain ABR latency. PMID- 1305635 TI - Event-related prolongation of induced EEG rhythmicities in experiments with a cognitive task. AB - Since we consider evoked potentials (EPs) and event-related potentials (ERPs) as an ensemble of induced rhythmicities we investigated "sensory" evoked potentials (EPs) and "cognitive" event-related potentials (ERPs) with respect to their frequency components (around 5 Hz and around 10 Hz). "Sensory" EP sessions consisted in standard EP measurements with tone bursts of 2000 Hz frequency. Prior to the subsequent "cognitive" sessions, the subjects were instructed to expect frequent 2000 Hz tones and rare 1950 Hz tones, the rare tones thus being difficult to detect. A further instruction was to count the number of the "rare" stimuli. Not a single tone of different frequency, however, was presented. The single trials were then analyzed with respect to their 5 Hz and 10 Hz components. Time-locking was investigated using a modified single sweep wave identification (SSWI) method. Depending on features of the prestimulus EEG, it was observed that theta (4-7 Hz) and alpha (7-13 Hz) responses were prolonged in the case of "cognitive" sessions. We believe that the prolonged endogenous ERP components are induced rhythmicities triggered by additional information processing, when a high degree of uncertainty has to be resolved during our experimental conditions. For the analysis and visualization of these phenomena, the combination of digital filtering and SSWI showed relevant advantages in comparison to other methods. PMID- 1305634 TI - Pineal and habenula calcification in schizophrenia. AB - Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions. PMID- 1305636 TI - The direction of the conditioned natural killer cell response can be re-directed with indomethacin and/or handling. AB - We have used the pairing of camphor odor conditioned stimulus (CS) and injection of poly I:C unconditioned stimulus (US) in a short 3 day single trial conditioning paradigm. Conditioning was done by exposing mice to the CS/US combination on day 0 and reexposing the conditioned animals to the CS on day 2. This results in a conditioned augmentation of the natural killer (NK) cell response. Indomethacin treatment and/or handling stress induced by simply measuring rectal temperature was found to dramatically alter the direction of the conditioned NK cell response. Conditioning of indomethacin treated mice produced a conditioned suppression of the NK cell response mimicking a conditioned tolerance response. If handling stress was superimposed on day 2 the conditioned suppression response was replaced by a conditioned augmentation of the NK cell response. Even with one trial conditioning, drugs and handling stress can serve as additional cues to alter the direction of the conditioned response. The studies also show that the conditioning of the fever response is independent of conditioning of the NK cell response. PMID- 1305637 TI - Enkephalins, brain and immunity: modulation of immune responses by methionine enkephalin injected into the cerebral cavity. AB - There is a large number of interactions at molecular and cellular levels between the nervous system and the immune system. It has been demonstrated that the opioid neuropentapeptide methionine-enkephalin (Met-Enk) is involved in humoral and cell-mediated immune reactions. Met-Enk injected peripherally produces a dual and dose-dependent immunomodulatory effect: high doses suppress, whereas low doses potentiate the immune reactivity. The present mini-review concerns the immunological activity of Met-Enk after its administration into the lateral ventricles of the rat brain, and describes the extraordinary capacity of centrally applied Met-Enk to regulate/modulate the immune function. This survey is composed of sections dealing with (a) the role of opioid peptides in the central nervous system (CNS); (b) the activity of opioid peptides in the immune system; (c) the application of Met-Enk into the cerebral cavity; (d) the influence of centrally administered Met-Enk on nonspecific local inflammatory reaction; (e) the effect of Met-Enk injected intracerebroventricularly (i.c.v.) on specific delayed hypersensitivity skin reaction, experimental allergic encephalomyelitis, anaphylactic shock, plaque-forming cell response, and hemagglutinin production; (f) the central antagonizing action of quaternary naltrexone, an opioid antagonist that does not cross the brain-blood barrier, on Met-Enk-induced immunomodulation; (g) the alteration of immune responsiveness by i.c.v. injection of enkephalinase-degrading enzymes; (h) the participation of the brain-blood/blood-brain barrier in the CNS-immune system interaction; and (i) the role of opioid receptors in immunological activity of Met-Enk. A hypothesis has been advanced for the reaction of Met-Enk and opioid receptor sitting on the cell membrane. This concept suggests that the constellation of chemical residues of enkephalin and receptor in the microenvironment determines the binding between the opioid partners. The plurality of conformational structures of enkephalins and receptors makes possible their involvement in a variety of processes which occur in different physiological systems, including the nervous system and the immune system, and intercommunications between the two systems. PMID- 1305638 TI - Anaphylactic shock in neuropsychoimmunological research. AB - Anaphylaxis appears to be an excellent experimental model for investigating the interactions between central nervous system (CNS) and immune system. Both afferent and efferent regulatory pathways of anaphylactic response are well characterized. The potent mediators of anaphylactic shock, such as histamine and serotonin, are at the same time neurotransmitters, acting in the CNS, and regulators/modulators of the immune system, since receptors for these substances exist on the membrane of the cells of the immune system. In this article the results of studies on the relationship between anaphylaxis and CNS, performed by both pioneers and contemporary investigators, are briefly reviewed. Recent experiments done in our laboratory are presented, which showed that (a) anaphylactic shock can be induced by intracerebroventricular administration of the shocking dose of antigen; (b) rats can learn to associate the induction of anaphylactic shock with neutral stimuli from the environment; and (c) stress in the form of electric tail-shocks reduces the intensity of anaphylactic shock. PMID- 1305639 TI - Measuring chaos in the brain: a tutorial review of nonlinear dynamical EEG analysis. PMID- 1305640 TI - Asymmetrical relationships between the right and left heights of the sylvian end points in right- and left-pawed male and female cats: similarities with planum temporale asymmetries in human brain. AB - Asymmetry in the height of the right (R) and left (L) Sylvian end points was studied in right- (RH) and left-pawed (LH) male and female cats. Sylvian height was described relatively to brain weight. An asymmetry coefficient (AC) was estimated (R - L/.5*R + L). There was no significant relationship between R + L Sylvian height and AC, in the total sample and in AC- (leftward asymmetry) brains. In AC+ brains (rightward asymmetry), R + L Sylvian height showed an inverse correlation with AC in RH cats, and a direct correlation in LH cats. There was an inverse correlation between left Sylvian height and AC in RH cats, but no correlation in LH cats. There was a direct correlation between right and left Sylvian height and AC. In AC- brains, left Sylvian height had no relation to AC, but there was a direct correlation between right Sylvian height and AC. In AC+ brains, left Sylvian height showed an inverse correlation with AC in RH males and females; a direct correlation only in LH male cats. Right Sylvian height showed a direct relation to AC+ values in RH and LH males and LH females (no correlation in RH females). The results supported the generalization that a brain symmetrical in a given region has more combined cortex than a brain that is asymmetrical for this region, only for RH cats, however (Galaburda et al., 1987). PMID- 1305642 TI - State-dependent peculiarities of cocaine-induced behavioral sensitization and their possible reasons. AB - To study determinants and possible reasons of cocaine-induced behavioral sensitization, locomotor effects of the drug (COC, 15 mg/kg, IP; 5 daily injections followed by a "challenge," four days later) and various stimuli associated (procedure of injection, placement in the test cage) and nonassociated (tail-pinch) with its administration were measured in rats under different experimental conditions. When COC was injected in quite conditions, two hours after animal habituation to the test cages, locomotor response to the first drug injection was only slightly higher compared to one of saline and these responses were relatively stable following repeated treatment (no sensitization). An enhanced locomotor response to the procedure of injection (needle prick) without changes in responsivity to other stimuli used were found in these COC-treated rats. When COC was injected in activated conditions (animal placement in test cages), locomotor response to the first drug administration was significantly higher compared to one of saline and COC used in the quiet state and it was enhanced following repeated treatment (sensitization). More intense locomotion associated with placement in test cages without any changes in responses to other stimuli was found in rats after this procedure of treatment. Thus, locomotor effects of COC and dynamics of its changes following repeated treatment depend upon the organism's functional state accompanying the drug's effect. Reinforcing action of COC determining development of interinfluence of its effects and ones triggered by environmental variables (learning based on conditioning) is considered as a proposed initial cause and a main mechanism both for enhanced reactivity to cocaine administered under conditions of its previous use and to various environmental events associated with previous cocaine effects. PMID- 1305641 TI - The pineal gland and the mode of onset of schizophrenia. AB - Recent studies suggest that abnormal melatonin functions may be implicated in the pathophysiology of schizophrenia. Since there is evidence that the presence of pineal calcification (PC) may relate, among other factors, to disturbances in melatonin secretion, I investigated in 23 chronic institutionalized schizophrenic patients the relationship of PC size on CT scan to the mode of onset of schizophrenia which carries both developmental and prognostic significance. Patients with gradual onset schizophrenia had PC size that was significantly larger than those with sudden onset (8.94 +/- 3.96 mm vs. 4.80 +/- 1.75 mm p < .025). These findings suggest that the nature of onset of schizophrenia may be influenced by the activity of the pineal gland, which may exert a role in the development and prognosis of the illness. PMID- 1305644 TI - A good training ground. PMID- 1305643 TI - An audit of resuscitation and anaesthesia during Operation 'Safe Haven'. AB - The Royal Navy combined Surgical Support Team deployed for six weeks to Northern Iraq. Eighteen casualties of civilian and military trauma required active resuscitation, 10 of whom were under the age of 16. Three died. Triage of multiple casualties was necessary on three occasions. The principles of Advanced Trauma Life Support (ATLS) were adopted and the experience is described under the ABCDE headings of the primary survey. Deficiencies of training and equipment are identified. Seventy one anaesthetics, administered to 52 patients, were audited prospectively in detail. Systolic blood pressure was significantly higher with isoflurane and controlled ventilation (ICV), compared with halothane and trichloroethylene (HTCV) (P < 0.05). ICV patients recovered more quickly than with HTCV (P < 0.05), but were significantly older and heavier (P < 0.05). Isoflurane should replace the standard halothane/trichloroethylene combination. Controlled ventilation or ketamine anaesthesia allowed satisfactory SpO2 on air alone. With controlled ventilation, anaesthesia was entirely satisfactory for children down to 6.5 kg. Local anaesthetic procedures were useful. The entire anaesthetic drug cost was only 127 pounds. Three patients received a degree of intensive care. Recommendations are made to improve future outcome, but sophisticated resuscitation, anaesthesia and monitoring is now possible in the front line. PMID- 1305645 TI - The effect of manpower and medical facility reduction on surgical practice during the Gulf Conflict 1991. AB - The General Surgical admissions to Royal Naval Hospital, Stonehouse from 1 April 1990-31 March 1991 were audited. This period included the Gulf War. There remained throughout the build-up to Operation Desert Storm, and during the actual conflict, a requirement to treat Service personnel as well as maintaining surgical training. This paper shows that both criteria were met despite reduced medical manpower and facilities. PMID- 1305646 TI - Rhegmatogenous retinal detachment in Royal Naval personnel: a retrospective study. AB - A retrospective study was conducted to assess the various factors thought to influence the outcome of retinal detachment in RN personnel. A description of retinal detachment and its management, aimed at non-specialists, is given in the introduction. In the study period eight Servicemen had rhegmatogenous retinal detachments. All underwent conventional detachment surgery, but two required two further operations including vitrectomy. Important features of each patient's detachment are discussed, as is post-operative progress. All patients spent a considerable time away from duty and three were discharged from the Service on medical grounds. Poor outcome could be related to myopia, trauma, delay in presentation to primary care, the number of operations performed and to post operative complications. Advice is given regarding assessment and management of suspected cases by non-specialists. It is hoped that reporting this study will increase awareness within the RN of retinal detachment as a sight-threatening condition. PMID- 1305647 TI - The obstetric course of elderly primigravidae--a review. AB - An increasingly large number of women are now delaying the start of their families until they reach the age of 35 years or older. They are then known as elderly primigravidae in obstetric parlance. This paper reviews recent literature and reports on a retrospective survey conducted by the author of such women at an RAF hospital and presents the findings concerning their ante-natal, intra-partum, post-partum and neonatal outcomes. PMID- 1305648 TI - Malta and the British Navy: the medical connection during the nineteenth century. Part I. The establishment of the Naval Hospital at Bighi. PMID- 1305649 TI - Clinical nutrition in paediatrics. PMID- 1305650 TI - Helicobacter pylori infection in children. PMID- 1305651 TI - The genetic basis of cancer. AB - The genetic basis of human cancer is well established, although much work remains to be done to unravel the mechanisms of carcinogenesis. Multiple genetic alterations appear to the hallmark in the adult cancers. Molecular cloning and characterization of the amplified proto-oncogenes and mutated recessive oncogenes would shed light on the mechanisms involved in the initiation and progression of human cancer. New tests are likely to be available in the near future (for specific oncogenes) for the diagnosis and management of various forms of human cancer. PMID- 1305652 TI - Stealing in children. AB - Stealing is a common behavioural problem in children. The causes of stealing include a desire for possession, attention-seeking behaviour, revenge, a lack of discipline, poor parental role models, or significant psychological or psychiatric problems. With proper management, the tendency to steal resolves in most children. PMID- 1305653 TI - Cephalosporins in childhood bacterial meningitis. AB - Bacterial meningitis remains one of the most common life threatening infections of childhood. There exists a conventional therapy for this disease. However, with the increasing incidence of Haemophilus strains resistant to ampicillin and chloramphenicol and Streptococcus pneumonia strains relatively resistant to penicillin, alteration of current therapeutic regimens for meningitis may become necessary. Cephalosporins were considered as alternatives to the conventional therapy for the treatment of bacterial meningitis during the past decade. However, there are still some discrepancies on the use of these against some organisms despite the advent of the cephalosporins. Thus, a review article analyzing quite a number of reliable clinical trials related to cephalosporins for the treatment of bacterial meningitis during the past decade to date is introduced. PMID- 1305654 TI - Renal replacement therapy in children: viable options in Singapore. PMID- 1305655 TI - Approaching "asthma" in pre-school children. AB - Respiratory illnesses are the most common cause of morbidity throughout childhood. In the pre-school age group, there is uncertainty about when to attribute symptoms to asthma and when to use asthma therapy. This article reviews these problems and suggests a basis for the use of medication. PMID- 1305656 TI - A saved little heart--transposition of great arteries. PMID- 1305657 TI - A review of congestive heart failure. PMID- 1305658 TI - Paediatric heart murmurs--innocent or guilty? PMID- 1305659 TI - Non-surgical closure of patent ductus arteriosus with the Rashkind PDA occluder system. AB - Transcatheter closure of Patent Ductus Arteriosus (PDA) was done in 18 children using the USCI Rashkind PDA occluder system. Patient age ranged from 1.2 to 14 years and their weights ranged from 8 to 36 kg. Isolated restrictive PDA was present in 15 patients; 3 had additional cardiac defects. The diameter of the PDA ranged from 2 to 6 mm as determined by lateral aortogram. PDA occlusion was successfully done in all 18 children. Ten 12 mm and eight 17 mm occluders were implanted with no complications. Post-implant aortogram showed complete ductal closure in 6 and trivial or small residual ductal flow in 12 cases. Doppler color flow mapping done within 3 days of the procedure showed complete ductal closure in 9, 8 had trivial ductal flow and 1 had small ductal flow. Transcatheter technique using a Rashkind PDA occluder system is a safe and effective method of non-surgical PDA occlusion. PMID- 1305660 TI - The use of blood glucose/cerebrospinal fluid glucose ratio in the diagnosis of central nervous system infection in infants and children. AB - The diagnosis of bacterial meningitis can be difficult nowadays when antibiotics are freely used in infants and children with fever due to infection, so that a positive smear or culture may be difficult to achieve. In areas where sophisticated methods of diagnosis may be hard to come by, the simple procedure of simultaneously estimating the blood and cerebrospinal fluid (CSF) glucose levels may be helpful in distinguishing bacterial meningitis from viral meningitis. 74 proven cases of bacterial meningitis and aseptic meningitis were investigated prior to treatment. There were 36 cases of bacterial meningitis and 38 cases of aseptic meningitis. The CSF glucose/plasma glucose ratio was calculated for each patient. The cases were divided into two groups; Group A with CSF glucose/plasma glucose ratio of (0.38-2.0) and Group B with CSF glucose/plasma glucose ratio of (0.1-0.35). In Group A, two out of 59 cases died while in Group B, nine out of 15 died (p < 0.01). 44 out of 59 in Group A recovered fully while only two out of 15 in Group B were cured (p < 0.01). It was also found that 54.2% in Group A were admitted in deep coma compared with 86.7% in Group B (p < 0.05) and 25.4% in Group A were admitted with seizures while 66.7% in Group B had convulsion (p < 0.01). Hence, a low CSF glucose/plasma glucose ratio was associated with a poor outcome. The mechanisms responsible for these findings are discussed especially with reference to the blood-brain barrier (BBB).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305661 TI - Birth trauma and nasal septal deformity in neonates. AB - The prevalence of nasal septal deformity and its relationship with the different types and difficulty of delivery were studied in a randomised group of newborns at the Maternity Hospital Kuala Lumpur between 1st November 1989 to 31st January 1990. Out of a total of 674 noses examined using the otoscope, 147 (21.8%) were found to have nasal septal deformity. There was no significant difference in the prevalence of nasal septal deformity in the different types of delivery. There was also no significant increase in the prevalence of nasal septal deformity with increasing degree of difficulty of the delivery. Therefore, we cannot then attribute parturition pressures or birth trauma as the etiology of these congenital nasal septal deformity. Nevertheless a policy of routine screening in view of early correction is advocated to decrease the morbidity associated with this deformity in newborns and children. PMID- 1305662 TI - A clinical study of obstructive jaundice among Singapore infants. AB - Fifty infants with obstructive jaundice were reviewed. Other than jaundice, hepatomegaly and splenomegaly were the other common presentations. The mean age of referral was 9.4 weeks. This was unsatisfactory as the prognosis depends on the age of corrective surgery. Majority of the non surgical cholestasis were due to idiopathic hepatitis. These patients did well as all of them were asymptomic and had no evidence of liver disease at 2 years of age. PMID- 1305663 TI - Chronic inflammatory bowel disease in Singapore children. PMID- 1305664 TI - Long term endocrine complications of acute leukemia therapy--a case report. AB - We report a patient with acute lymphoblastic leukemia who underwent treatment comprising chemotherapy, radiotherapy (cranial and testicular) and then a bone marrow transplant from an identical twin. He was cured of his leukemia and has been disease-free for nine years. With long term survival, there were problems, notably those of growth and endocrine insufficiency, which needed special considerations in management. PMID- 1305665 TI - Etretinate treatment for Harlequin baby. AB - This report of a Harlequin foetus surviving is due essentially to two factors. a) the intensive care provided to the erythrodermic infant, looking after its nutrition, temperature control and controls of infection and b) the use of a new synthetic Vitamin A acid--Etretinate in the management of dyskeratinisation syndromes. As this is of autosomal recessive inheritance, besides genetic counselling, Singapore has to develop its prenatal diagnostic techniques viz amniocentesis and ultrasound studies of the skin, to detect dermatological problems. PMID- 1305666 TI - Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome)--a case report and review. AB - We report two brothers with anhidrotic ectodermal dysplasia (AED). AED is characterised by a triad of inability to sweat dental abnormalities and hypotrichosis. Although rare, it is important to diagnose this condition as it may lead to considerable morbidity and mortality if unrecognised. The typical features of this entity as described in the literature and as seen in our patients are emphasized as increased awareness can lead to early diagnosis and better prognosis. PMID- 1305667 TI - The Moebius sequence--report of a case and a short annotation. AB - A Malay baby with multiple cranial nerve involvement consistent with the Moebius sequence (syndrome) is reported. He also had many non-Central Nervous System (CNS) related defects which include limb reduction defects and the Poland sequence. A short annotation and the spectrum of this disorder are presented. In view of many reported related disorders, Moebius sequence may occur as a part of a broader pattern of malformation. PMID- 1305668 TI - The pressure-dependent nature of the rash in Henoch Schonlein purpura. AB - A 10 month old girl with Henoch-Schonlein purpura (HSP) developed a rash predominantly on the anterior aspect of the knees. The authors speculate that this distribution of the rash was due to the pressure effects consequent to crawling and propose that the distribution of the rash in HSP should be described as pressure-dependent rather than merely gravity-dependent. The therapeutic implications of pressure-dependency in HSP are discussed. PMID- 1305669 TI - Post-streptococcal glomerulonephritis with minimal abnormalities in the urinary sediment. AB - Post-streptococcal glomerulonephritis (PSGN) classically presents with hypertension, edema, macroscopic hematuria, acute renal failure, proteinuria, and an active urine sediment with red blood cells and red blood cell casts. A patient who developed PSGN but who had only minimal and transient abnormalities in the urinalysis is reported. Physicians should be aware that a normal urinalysis does not rule out the diagnosis of PSGN. PMID- 1305670 TI - Efficacy of Zaditen (ketotifen) in wheezy infants and young children. AB - This was a double-blind, randomised evaluation of the efficacy and safety of Zaditen in comparison with placebo in infants and young children (aged 6-36 months). These children either had (i) at least 2 episodes of wheezing over 8 weeks, or (ii) persistent wheeze over 4 weeks, prior to entering into the study. In the doctor's opinion, the group treated with Zaditen had more improvement in symptomatology (p < 0.05). They were more likely to have reduced or discontinued bronchodilators. They showed trends of improvement of symptom scores in night cough, wheeze and sputum production. These differences, however, did not reach statistical significance. There were no major adverse reaction of note. PMID- 1305672 TI - Chemoprevention of premalignant and early malignant lesions of the bladder. PMID- 1305671 TI - Development of chemopreventive agents for bladder cancer. AB - The term cancer chemoprevention refers to the prevention or prolongation of carcinogenesis by intervention with drugs prior to the malignant (i.e., invasive) stage. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch of the National Cancer Institute. Neoplastic lesions of the urinary bladder present a unique opportunity for evaluating chemopreventive agents because of (1) the accessibility of the lesions to observation and biopsy, and (2) those patients who have been successfully treated for a primary lesion represent a population at unusually high risk for recurrence and/or progression. Although 70-80% of bladder cancers initially present as superficial, papillary transitional cell neoplasms with limited potential for invasion, the incidence of recurrence is high after resection (60-75%). Recurrent tumors are highly unpredictable, and may be of higher grade or stage (progression). Although recurrence is responsible for high treatment-related morbidity, progression represents the greatest potential for mortality. Thus, potential chemopreventive agents considered here would modulate bladder carcinogenesis from initiation of normal-appearing tissue through progression of superficial tumors. Clinical trials of chemopreventive drugs involve healthy target populations, and the endpoints are reduced cancer incidence or mortality, reduced/eliminated precancerous lesions or increased latency, with none to minimal toxicity. Since cancers may not appear for 20-30 years, two of the most difficult aspects of testing these drugs in intervention trials are the long observation periods and large study populations required to measure cancer incidence reduction. However, observing the regression or recurrence of superficial bladder lesions (TIS, T1, Ta) requires relatively short time periods. Thus, these lesions lend themselves to the investigation of intermediate biomarkers, defined as morphologic and/or molecular alterations in tissue between initiation and tumor invasion. It is hypothesized that modulation of one or more biomarkers would interrupt carcinogenesis and result in a decrease in cancer incidence. Thus, evaluation of biomarkers as surrogate endpoints would allow bladder trials to be of even shorter duration, use fewer subjects and be lower in cost. In addition, intermediate biomarkers could predict which superficial lesions (or normal appearing tissue) have the greatest potential for neoplastic progression. Development of strategies for the design of intervention trials for bladder cancer and review of the current status of intermediate biomarkers in the bladder, and methods for their validation, are major objectives of this workshop. PMID- 1305673 TI - Intravesical BCG: current results, natural history and implications for urothelial cancer prevention. AB - Bacillus Calmette-Guerin (BCG) has been shown in randomized trials to be the most effective agent against superficial bladder tumors. BCG therapy prevents or reduces tumor recurrences, abrogates tumor progression and improves survival over surgery alone. The optimal BCG schedule varies among patients, reflecting a heterogeneous tumor population. Multifocality, high grade (G2,3) and T1 tumors are risk factors for tumor recurrence or invasion. Patients presenting with such features are most likely to benefit from BCG. An incomplete response to BCG portends a high risk of tumor progression. Non-responders have a 40-60% risk of developing muscle invasion or metastases within 10 years, compared with 10-15% for BCG responders. Further, 80% of non-responders progress in the bladder within 3-5 years. After 5 years, relapses are more common in the prostate (13-35%) and upper collecting system (15-33%); one-half of these are invasive tumors. This suggests that intense therapy directed at premalignant and early bladder lesions coupled with a chemoprevention strategy designed to protect the whole urothelium will be required to reverse a pan-urothelial tumor diathesis. PMID- 1305675 TI - Chemotherapy resistant transitional cell carcinoma as a target for chemoprevention. AB - alpha-Interferon combined with 5-fluorouracil results in significant antitumoral activity in metastatic bladder carcinoma refractory to standard MVAC chemotherapy. As a single agent, alpha-interferon is ineffective for invasive or metastatic disease, but appears to contribute to the increased response rate of patients with invasive chemotherapy-refractory disease. Although most patients with superficial bladder carcinoma will not develop invasive disease, patients in complete remission from invasive disease are at high risk for relapse. In vitro assays indicate that fenretinide (4-HPR), alpha-interferon, and 5-fluorouracil possess significant antitumoral activity in human transitional cell carcinoma (TCC) lines. Some features of postchemotherapy-refractory TCC are similar to those of initial superficial disease (sensitivity to biological therapy). The biological study of patients with residual postchemotherapy disease may permit the development of strategies which will prevent the recurrence of malignancy within the bladder following an initial complete remission, in addition to developing strategies for the selection and treatment of patients with high risk superficial disease. PMID- 1305674 TI - Superficial bladder cancer: diagnosis, surveillance and treatment. AB - Approximately 70% of all bladder cancers are superficial at the time of presentation. Superficial bladder cancer includes tumors confined to the urothelium (clinical stage Ta) or lamina propria (stage T1) and flat carcinoma in situ (stage Tis). Because the biological behavior of bladder neoplasms is variable, several important prognostic factors must be addressed. Multivariate analyses have shown that factors predictive of tumor recurrence and tumor progression include multifocal tumors, high grade tumors, T1 tumors and positive urinary cytology after transurethral resection (TUR). The patient with superficial bladder cancer should be monitored via endoscopy supplemented by urinary cytology, using either voided or bladder irrigation specimens and urinalysis. Frequent intravenous urography is not required, even in high grade tumors, as long as the clinical and pathologic studies remain negative and the patient is asymptomatic. The "gold standard" of treatment for superficial bladder carcinoma is TUR of the entire tumor. Despite TUR, new tumors will occur in approximately 50% of all patients; those at highest risk for tumor recurrence and progression require adjuvant intravesical therapy after TUR. A variety of drugs are used as intravesical therapy, including thiotepa, mitomycin C, doxorubicin hydrochloride, Bacillus Calmette-Guerin (BCG), epirubicin, and interferon. Although associated with the most toxicity, BCG appears to be the most efficacious agent in increasing the time to recurrence and progression and in reducing the recurrence rate. PMID- 1305676 TI - New opportunities for screening and early detection of bladder cancer. AB - In the United States, over 51,000 new cases of urinary bladder tumors are diagnosed annually. Approximately 75-85% of all newly diagnosed cases are superficial transitional cell carcinomas (TCCs). Incidence is highest (80% of the cases) in the 50-79 year age group. Recent studies have reported that 21-25% of risk for bladder cancer among United States white males is due to occupational exposure. The DuPont Chambers Works in Deepwater, New Jersey, was a major producer of two chemicals now known to be human bladder carcinogens (beta naphthylamine and benzidine) as well as two suspected human bladder carcinogens [ortho-toluidine and 4,4'-methylene- bis,2-chloroaniline (MOCA)]. Between 1954 and 1982, DuPont screened 1723 exposed employees annually at the Chambers Works using the Papanicolaou test for urinary cytology and microscopic urinalysis. A review of the prior screening program found that employees who developed bladder cancer during this time period were approximately twice as likely to have had hematuria than those comparably exposed who did not develop bladder cancer. Building on this finding, a three-year screening study evaluated a home self-test for microscopic hematuria to aid early detection of treatable urologic conditions among exposed workers at this chemical plant. Every six months, subjects tested their urine at home for 14 consecutive days, for the presence of blood. A high degree of adherence to our protocol (over 92% completed and returned the self testing record) as well as high compliance with repeat screening (85% returned for screening in subsequent quarters) demonstrated good acceptance and performance of the recommended schedule of self-testing. Through the first 7 periods of screening, two new cases and one recurrence of TCC of the bladder were detected. PMID- 1305677 TI - Chemoprevention of experimental bladder cancer. AB - The chemopreventive efficacy of several compounds was evaluated in the N-butyl-N (4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary bladder cancer model using C57BL/6 x DBA/2F1 (BDF) male mice. Compounds were administered in a defined semipurified diet (AIN-76-A) either as single agents or in combination. As single agents and at the doses employed, 2-alpha-difluoromethylornithine (DFMO), piroxicam, oltipraz, and sodium molybdate effectively inhibited the incidence of transitional cell carcinoma (TCC). 4-Hydroxyphenyl retinamide (4-HPR) was ineffective. Body weight gain and survival was not affected by the doses of agents used. Combinations of two agents which increased efficacy were 4-HPR+DFMO, DFMO+piroxicam, 4-HPR+oltipraz, and DFMO+oltipraz. Three-agent combinations which showed enhanced efficacy against TCC induction were 4-HPR+Na molybdate+DFMO, 4 HPR+DFMO+piroxicam, and 4-HPR+DFMO+oltipraz. Although the three-agent combinations were, for the most part, no more effective than the two-agent combinations at the doses employed, all combination regimens significantly reduced bladder cancer incidence even when single agent administration did not. PMID- 1305678 TI - Activity of 4-HPR in superficial bladder cancer using DNA flow cytometry as an intermediate endpoint. AB - The ability of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in a pilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (range 0-36). The median follow-up period was 12 months (range 3-31) in the 4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased from 7/12 (58%) to 5/11 (45%) in the 4-HPR group, but increased from 7/17 (41%) to 10/17 (59%) in the control group. In patients with stable diploid profiles, mean (+/- SE) S-phase and G2+M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2 +/- 4.1% to 7.5 +/- 3.3% and 10.3 +/- 2.2% to 5.2 +/- 0.4%, respectively. The same parameters in the control group changed from basal levels of 14.6 +/- 3.4% to 12.4 +/- 2.7% and 9.8 +/- 1.6% to 12.6 +/- 1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%) during follow-up. Impaired adaptation to darkness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305679 TI - 13-cis-retinoic acid in chemoprevention of superficial bladder cancer. The National Bladder Cancer Group. AB - Animal studies indicate that 13-cis-retinoic acid (CRA) inhibits bladder tumor growth and is effective in treating patients with serious dermatologic disorders. A trial of CRA in patients at high risk for recurrent Ta, T1 tumors was initiated at an experimental dose of 0.5 mg/kg/d in three divided doses, increasing to 1 mg/kg/d at four weeks. Treatment of twenty eligible patients lasted for six months with an additional 24 month follow-up period. One patient was later excluded due to toxicity resulting in an early dose reduction. Eight patients stopped treatment before three months; of these five, had recurrences within three months, one developed pulmonary metastasis, and one developed a T2G3 tumor. Four patients stopped treatment between three and six months; three of them had recurrences before one year and one had no evidence of disease at seven years. Seven patients completed the course; of these three had recurrences within six months, and three more had recurrences at 8, 15, and 45 months, respectively. Toxicity was nearly universal; cheilosis, conjunctivitis, pruritus, joint and eye pain, flashing lights, and erythrocyte sedimentation rate (ESR) over 60 were all noted. The lack of positive results and the frequency and severity of toxicity led to termination of the study. PMID- 1305680 TI - A prospective clinical trial of difluoromethylornithine (DFMO) in patients with resected superficial bladder cancer. AB - Difluoromethylornithine (DFMO) is a promising chemopreventive agent which is excreted unchanged in the urine, is active in vivo against superficial bladder cancer in animal tumor model systems, and has cytotoxic activity in vitro against superficial bladder cancer cells. Thus, DFMO may be particularly efficacious in preventing the development of bladder tumors and/or for the therapy of established superficial bladder cancer. To examine this hypothesis, an intergroup clinical trial is currently accruing patients with cystoscopically resected superficial bladder cancer (who would otherwise simply be observed). While the primary goal of this protocol is to define a daily dose of DFMO having little or no toxicity for use in future randomized chemoprevention trials, the rate of recurrent bladder tumors will also be followed in the hope that DFMO will inhibit the development of recurrent bladder cancers. PMID- 1305681 TI - Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention. AB - Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in host antitumor immunity. For example, high levels of tissue PGE2 are frequently associated with suppression of immune surveillance and killing of malignant cells. Conversely, immune responses are generally enhanced by drugs that inhibit prostaglandin synthesis. PGE2 can act as a feedback inhibitor for cellular immune processes, such as T-cell proliferation, lymphokine production, and cytotoxicity. This effect is also seen for macrophage activity and natural killer cell toxicity. In general, either increased production of PGE2 or increased sensitivity to normal amounts of PGE2 results in depressed cellular immunity. Cyclooxygenase inhibitors (NSAIDs) such as piroxicam which decrease PGE2 production can stimulate cellular immune function both in vitro and in vivo. A variety of tumor cell lines and human malignancies produce large quantities of prostaglandins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1305682 TI - Mechanisms of chemoprotection by oltipraz. AB - 1,2-Dithiole-3-thiones are five-membered cyclic sulfur-containing compounds with antioxidant, chemotherapeutic, radioprotective and cancer chemoprotective properties. One substituted dithiolethione, oltipraz [5-(2-pyrazinyl)-4-methyl 1,2-dithiole-3-thione], originally developed as an antischistosomal agent, has recently been observed to protect against chemically induced carcinogenesis in lung, trachea, forestomach, colon, breast, skin, liver and urinary bladder in rodents. The induction of electrophilic detoxication enzymes, which result in diminished carcinogen-DNA adduct formation and reduced cytotoxicity, appears to be an important component of the anticarcinogenic action of oltipraz and other dithiolethiones. Phase I trials of oltipraz are presently underway in the United States. Subsequent trials might be most appropriately targeted towards individuals at high risk for occupational or environmental exposures to genotoxic carcinogens. PMID- 1305683 TI - Intervention strategies for chemoprevention of bladder cancer. PMID- 1305684 TI - Bladder cancer from a perspective of 40 years. AB - The key events leading to a better understanding of the natural history of urothelial tumors of the bladder are summarized. These were: the recognition of flat carcinoma in situ and related lesions (intraurothelial neoplasia) as principal sources of invasive cancer; identification of the unique structure of the urothelium; analysis of DNA content and the recognition of two pathways of urothelial tumors. A brief comment on the current status of immunologic and molecular genetic markers is appended. PMID- 1305685 TI - Natural history of early bladder cancer. AB - Non-invasive transitional cell carcinoma (TCC) occurs as two distinct growth patterns, papillary and non-papillary (flat), which display significant differences in biologic potential. Papillary carcinoma usually presents as a low grade lesion which frequently recurs multiple times prior to invasion; conversely, non-papillary (flat) carcinoma in situ is usually high-grade at presentation (carcinoma in situ) and frequently associated with invasion. These lesions may occur together, although papillary cancer is more easily visualized cystoscopically due to its exophytic growth; flat carcinoma in situ is often cystoscopically invisible. This report reviews existing data concerning the prognostic value of pathologic grading and staging of non-invasive and early invasive TCC. Emphasis is placed on those studies reporting surgical treatment rather than other forms of treatment. PMID- 1305686 TI - Pathology of carcinoma in situ of the urinary bladder and related lesions. AB - In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationale Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305687 TI - Papillary tumors of the bladder. AB - The most common neoplasms of the urinary bladder are papillary tumors that vary histologically and cytologically from very well differentiated to highly anaplastic patterns. Biologic behavior of these tumors is closely correlated with morphology, so that cytologically benign tumors (papillomas) are benign in behavior, and increasing anaplasia is associated with increasing clinical aggressiveness. By this definition, 20% or more of bladder tumors should be classified as papillomas. The development of carcinoma occurs in a series of steps, progressing through atypia and carcinoma in situ to invasion. Finally, evidence is presented to show that invasive carcinoma often begins from areas of flat carcinoma in situ associated with, but not within, co-existing papillary tumors. PMID- 1305688 TI - Blood group antigens in normal and neoplastic urothelium. AB - The ABO and Lewis blood group antigens are cell surface carbohydrate determinants formed by the sequential addition of saccharides to precursor backbone structures of membrane lipids and proteins. Suppression of normally active glycosyltransferases results in the absence of antigens that are normally expressed. ABH antigen deletion in malignant and premalignant urothelium has been extensively evaluated; it appears to correlate with significantly higher rates of tumor recurrence and disease progression. However, we have recently shown that the ABH blood group system is differentially expressed in the normal urothelium of secretors in contrast to nonsecretor individuals. The normal urothelium of nonsecretors does not express A, B or H determinants; therefore, deletion of ABH antigens can only be ascertained in secretor individuals. Although nonsecretors only comprise 22-24% of the population, this observation mandates a reevaluation of earlier studies. Deletion of A, B or H antigens is noted in carcinoma in situ (CIS), and in invasive and metastatic transitional cell carcinoma (TCC) of secretor individuals. Increased synthesis or activation of normally quiescent glycosyltransferases in bladder tumors can result in the expression of aberrant tumor-associated blood group antigens. Immunohistochemical analysis has demonstrated that Lewis X (Le(x)) is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas, CIS and TCC expressed Le(x) in 84% of cases, regardless of grade, stage, blood type or secretor status of the individual. The presence of Le(x)-positive cells in bladder lavage specimens enhanced the detection of urothelial tumor cells, correctly identifying bladder tumors in 253/293 (86%) cases compared to a 63% sensitivity for cytology alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305689 TI - Epidermal growth factor and its receptor: markers of--and targets for- chemoprevention of bladder cancer. AB - Epidermal growth factor (EGF) is excreted in urine in high concentrations in a biologically active form. Several lines of evidence indicate that EGF plays a role in transitional cell carcinoma (TCC) development and growth. These include: (1) EGF in the normal urine of rats promotes chemically initiated TCC; (2) EGF in normal human urine stimulates the clonal growth of human TCC cells in vitro; (3) EGF stimulates the in vitro growth of human TCC cells, but not normal human urothelial cells; (4) the density and distribution of the EGF receptor (EGF-R) on human urothelial tissues permits significant access of premalignant, dysplastic, and malignant cells to EGF; and (5) the concentration of EGF in the voided urine of patients with TCC is reduced, implying that EGF may be "extracted" from urine by the greater number of EGF-Rs in patients with urothelial malignancy. Abnormal expression of the urothelial EGF-R and/or altered excretion of EGF may well precede overt evidence of TCC and thus may serve as markers of risk or exposure. Similarly, reversion of EGF-R expression or the return of excreted EGF to normal levels may provide a marker of response for preventive and therapeutic strategies. Interference with the EGF/EGF-R interaction through dietary or pharmacological manipulations of the urine, or via targeting strategies employing intravesical administration of conjugated toxins or isotopes is already being employed in experimental and clinical studies. These approaches offer promising new tools in the detection, monitoring, prevention, and management of early stage bladder cancer. PMID- 1305690 TI - Alterations in antigen expression in superficial bladder cancer. AB - Bladder cancer can be viewed as a prototype for carcinogen-induced neoplasia. This has been demonstrated experimentally in a variety of systems and in man through epidemiological studies of occupational exposure to putative carcinogens. The natural history of this neoplasm demonstrates recurrence in time and space, i.e., multifocal disease. This clinical scenario is precisely what would be expected if a target tissue, e.g., urothelium, was continuously exposed to a weak carcinogen. The detection of gross disease is clinically easy. However, the ability to intervene at early stages and monitor the success of this treatment requires the definition of early markers for bladder cancer. Integrins are a family of cell surface proteins, many of which function as receptors for extracellular matrix components. Normal epithelial cells express the integrin alpha 6 beta 4 in association with an anchoring structure known as the hemidesmosome. Urothelium expresses alpha 6 beta 4 on the basal layer of cells similar to the distribution seen on other epithelial surfaces. Even early stages of bladder cancer demonstrate an alteration in the expression of this integrin. Low-stage bladder tumors express alpha 6 beta 4 diffusely throughout the tumor as well as at the invading margin. Altered expression of alpha 6 beta 4 may be an early marker for bladder cancer which may contribute to an invasive phenotype. A second potential marker is detected by DD23, an IgG1 murine monoclonal antibody triggered by the immunization of a BALB/c mouse with a fresh human bladder tumor specimen. The antigen detected by DD23 is not present on normal urothelial specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305691 TI - Altered RB expression is a prognostic clinical marker involved in human bladder tumorigenesis. AB - We are now beginning to understand the development of bladder cancer at the molecular level. Tumor evolution involves the interaction of both oncogenes and tumor suppressor genes. One of the key tumor suppressor genes in this process is the retinoblastoma (RB) gene. Much has been learned recently about the role of this gene in the tumor progression and prognosis of bladder cancer, although several questions are still unanswered. The progress made on this subject in our laboratory as well as others will be the focus of this report. PMID- 1305692 TI - Cytology. AB - Exfoliative cytology is a relatively sensitive, highly specific technique for the detection and diagnosis of bladder cancer, and for monitoring conservative treatment. Cytologic diagnosis is based on cellular changes in DNA content, chromatin structure, and metabolic activities which are characteristic of cancer cells and can be recognized in desquamated isolated cells or cell clusters. The cytologic techniques are most effective in identifying low stage flat or papillary carcinoma, but not cytologically benign papillomas or ulcerating invasive cancers that do not easily shed cancer cells. With the growing number of pathologists who, in recent years, have become skilled cytopathologists, urinary tract cytology has developed into an essential diagnostic tool for the urologist. PMID- 1305693 TI - Chromosome changes in early bladder neoplasms. AB - There are few cytogenetic studies of early (non-invasive) bladder cancer, particularly in situ carcinoma, due to technical difficulties in examining such lesions. The best approach is to extrapolate from chromosomal changes in more advanced cancers. Although no specific chromosomal changes have been established in either early or fully developed bladder cancers, certain recurrent anomalies have been encountered. Anomalies such as +1, +7, -9, 5q- or i(5p), 11p- and -Y appear to constitute part of the multistep carcinogenetic process by which clinically and pathologically recognizable bladder cancers develop. Since loss of part or all of chromosome 9 (-9) is a common and early cytogenetic event in bladder cancer, the detection of -9 in bladder washings or urine by fluorescence in situ hybridization (FISH) may be a promising test for early or recurrent bladder cancer. Although less frequent than -9, trisomy 7 (+7) is common enough to serve a similar purpose. In contrast, loss of the Y chromosome may indicate an advanced stage of bladder cancer. Thus, FISH studies utilizing probes for chromosomes 7, 9, and Y should yield cogent information to identify early bladder cancer. Cytogenetic (including FISH) studies combined with certain molecular approaches (e.g., p53 mutations detected immunochemically) may not only serve to differentiate early cancer from benign tumors or conditions, but may also help establish cancer stage. This would supply data of considerable usefulness to the clinician and pathologist. PMID- 1305694 TI - Evaluation of DNA flow cytometry as a screening test for bladder cancer. AB - At this present time, we feel that there is no role for DNA flow cytometry (FCM), or indeed DNA studies by any other method, to be used as a screening procedure for patients with no prior history of bladder cancer due to the high false positive rate found when monitoring exfoliated urothelial cells. On the other hand, for patients who have had a superficial transitional cell carcinoma (TCC), which has a documented 50% recurrence rate, and depending on pathological features, a progression rate from 7 to 45%, DNA FCM provides a sensitive method to predict future disease recurrence. It provides an extremely effective way to predict future progression and further acts as a method to monitor changes in the malignant potential of the patient's disease. For those patients with a past history of superficial TCC who develop abnormal ploidy without any overt tumor, 80% will, within the next four years, suffer a disease recurrence. For the patient who has a Ta TCC and receives intravesical Bacillus Calmette-Guerin (BCG), the development of abnormal ploidy in bladder washing specimens is the single best indicator for future disease recurrence. Similarly, a negative DNA FCM of a bladder washing at six months after intravesical therapy is an excellent predictor of no further occurrence. In patients with superficial TCC, ploidy of the initial and recurrent tumor predicts for future progression. Half of those patients with stage Ta bladder cancer with two successive aneuploid bladder tumors develop muscle invasive disease within one year, while three-fourths develop advanced disease within two years after recurrence of their second aneuploid lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305695 TI - Strategies of chemoprevention based on antigenic and molecular markers of early and premalignant lesions of the bladder. AB - Using monoclonal antibodies, we have identified a series of tumor-associated antigens selectively expressed on tumor subtypes with distinct clinical behaviours. The mucinous antigen M344 and the gp200 surface antigen 19A211 are preferentially expressed on papillary superficial tumors and carcinoma in situ lesions of the bladder. The combination of these two antigenic markers in immunocytology and flow cytometry studies of exfoliated cells has improved the sensitivity of detection for bladder tumors. Moreover, the detection of M344- and 19A211-positive exfoliated cells from previously treated but currently tumor-free patients appears to be predictive of tumor recurrence on follow-up. These results, as well as results of bladder mapping studies in tumor patients, suggest that these antigenic changes occur in a premalignant stage and may provide tools to monitor the efficacy of chemopreventive measures. Other markers, such as the surface antigen T138 and the soluble molecules autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF), are produced by primary or recurrent tumors with a higher metastatic potential. They may be useful in identifying high risk patients for distant failure. The highly restricted antigen 19A211 is also expressed on cervix condylomas and carcinoma. This observation led us to investigate a possible viral etiology of some bladder cancers. Using PCR techniques, we detected the presence of human papillomavirus (HPV) 16 DNA sequences in a significant proportion of bladder tumors. HPV positivity was inversely correlated with the presence of p53 mutations in exons 5-9 of the same tumors as measured by PCR-SSCP technique. This combination of markers may provide a basis for chemoprevention strategies targeted to distinct etiological events. PMID- 1305696 TI - Intermediate endpoint biomarkers for chemoprevention. AB - The understanding of intermediate endpoint biomarker expression in relation to the sequential events in bladder tumorigenesis establishes a useful approach for evaluating chemopreventive agents. Biomarkers may be genotypic or phenotypic and function as biomarkers of susceptibility, exposure, effect, or disease. This paper reviews several years of research on biomarkers and their use in monitoring chemoprevention therapy. In initial animal experiments, mice were dosed with N butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) while co-administering N-(4 hydroxyphenyl)retinamide (4-HPR). 4-HPR did not statistically reduce tumor incidence, but did affect tumor differentiation and, consequently, nuclear size and DNA ploidy. These results suggest that nuclear size and ploidy may function as intermediate endpoint biomarkers of effect for oncogenesis and that epigenetic as well as genetic mechanisms may be primary in the oncogenic process. Early biomarkers of effect which occur prior to genetic effects or chromosome aberration may portend a higher probability of being modulated by differentiating agents such as retinoids. In vitro studies demonstrated that RPMI-7666 cells cultured with a phorbol ester tumor promoter (12-O-tetradecanoyl-phorbol-13 acetate) could be redifferentiated with 13-cis-retinoic acid and dimethyl sulfoxide (DMSO). F-actin, a cytoskeletal biomarker with a presumed function in the epigenetic mechanisms of carcinogenesis, could also be normalized in HL-60 cells treated with 4-HPR or DMSO. A clinical evaluation of F-actin in patients with varying degrees of risk confirmed the value of F-actin as a differentiating biomarker useful for bladder cancer risk assessment. The clarification of when the phenotypic changes of F-actin occur in the oncogenic process was achieved when a variety of biochemical changes were mapped in the patients with bladder cancer. These studies confirmed that G-actin, a reciprocal form of F-actin, is increased relatively early in bladder cancer oncogenesis when multiple biomarkers are quantitated in the field, adjacent area, and the tumor. Comparison of each individual biomarker's expression from field, adjacent to tumor, and tumor, and subsequent cluster analysis of these biomarkers, indicated that the possible sequence of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G-actin, to p300 antigen, to epidermal growth factor receptor (EGFR), to p185 (neu oncogene product), to DNA aneuploidy and, finally, to visual morphology.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1305697 TI - Application of information systems to AIDS risk reduction. AB - Acquired immune deficiency syndrome (AIDS) is a specific group of diseases which are indicative of severe immunosuppression related to infection with the human immunodeficiency virus (HIV). In response to the epidemic, a variety of intervention and prevention has been instituted. In such intervention and prevention activities, the role played by information systems becomes more and more important. This paper describes the design and implementation of an information system for AIDS intervention and prevention. PMID- 1305698 TI - Training of health care personnel towards the implementation and use of electronic health care records using integrated imaging technology. AB - The hospital of the future will be a place in which Health Care providers of various disciplines will have access to all information about a patient in a timely fashion, and where the communication system will be able to cope with all information representations ranging through data, text, images and voice. Multimedia systems offer the facilities to cope with the specific problems of the mainly manual approach for the effective and efficient organization of information related to facts and findings in medical care. In this article we outline the training needs for future users of such systems. PMID- 1305699 TI - Training needs for information management: a national programme. AB - This paper briefly describes major changes in the, management and organization of the English National Health Service from 1985. The information consequences of those changes and the central programme necessary both to realize and to achieve them, are summarized. The requirements for training flowing from these developments are analysed, as are some of the obstacles to be overcome in meeting them. The national programme of training in information management, currently in its third year, is set out, and its particular aims described. PMID- 1305700 TI - Object-orientated DBMS techniques for time-oriented medical record. AB - In implementing time-orientated medical record (TOMR) management systems, use of a relational model played a big role. Many applications have been developed to extend query and data manipulation languages to temporal aspects of information. Our experience in developing TOMR revealed some deficiencies inside the relational model, such as: (a) abstract data type definition; (b) unified view of data, at a programming level; (c) management of temporal data; (d) management of signals and images. We identified some first topics to face by an object orientated approach to database design. This paper describes the first steps in designing and implementing a TOMR by an object-orientated DBMS. PMID- 1305701 TI - Design and implementation of computer-readable patient data cards--applications in Europe. AB - Computers have been widely accepted today as essential tools for handling and processing an ever-increasing flood of information. At the same time people, including patients and medical staff, are becoming more mobile and face the problem of interacting with the different computerized systems. We are also experiencing the acceptance of the small rectangular plastic cards as the instrument for vast numbers of transactions throughout the world. These factors have highlighted the possible attractions of machine-readable patient data cards that can be carried by the patients themselves. The patient data card is expected to provide quick reference information to any physician or health worker consulted by the carrier. This information should avoid duplication of diagnostic, therapeutic and prescription measures and help give a conveniently structured summary of the patient's medical history. Advances in technology have made it possible to move from the familiar credit card which can store only a limited amount of information, to new, similarly shaped cards with much greater capabilities. The basic technologies for patient data cards are examined. An analysis is then attempted of the possible information contents of such a card that could be used at a national and European level, and of the field trials in Europe so far. Questions of security and standardization are also addressed. A number of conclusions and recommendations are also made which are based on the experience gained from a relevant implementation attempted, and participation in a recent study undertaken by the EEC in the area. PMID- 1305702 TI - Portable medical records on microchip cards: the Tournai experiment. AB - A test of the use of microchip cards as portable medical records has been organized and evaluated in a small Belgian town. The portable record was accepted by patients and could be a useful innovation for emergency situations. A comparative evaluation of other portable media is needed. PMID- 1305703 TI - An entity-relation model for a tocho-gynaecology service. AB - There is a trend, both at national and European levels, towards the use of standards in hardware, software and communications. This implies a common root for the design of unified databases which will result in the homogeneity and interchangeability of data and knowledge. The technological solution exists and is imposed. The problem then is not the tools to be used as information support but how this information is organized and structured. According the the standards proposed by the Plan de Dotacion Informatica para la Asistencia Sanitaria (DIAS), and with respect to the problem of computer coverage of specialties, we present in this work an entity-relation model for a generic service within our project of integrally computerizing a tocho-gynaecology area. It is a multidisciplinary job between doctors and physicists where we use a planning strategy in order to identify the functions, processes and activities, making the traditional clinical management structure compatible with the one proposed. This means that if we want the introduction of the system to be effective, we have to make all the clinical and sanitary staff participate in the project. We must induce the need for change and carry out the process of change gradually, so that only a change in the support, and not in the organization, is initially perceived. PMID- 1305704 TI - MCHS: an application software for family welfare programmes. AB - At the level of first contact, a primary health care centre, information management is an unwieldy task, therefore health information systems are reported to be inadequate and weak. Microcomputers could improve information management at this level, but there is little success due to a lack of specialized application software. In this paper we describe software developed after a multi-centre systems analysis study, on an essential data set, to support the delivery of the public health programmes for family welfare, i.e. maternal health care, family planning and immunization programmes. The modular approach was taken to develop a common application software for information management use at multiple sites. The software is tested in a laboratory mode by retrospective data entry from sites in Sweden and in India. All the information could be entered and site-specific reports that were generated are compared. The software provided a common data collection format, an essential platform for outcomes research. PMID- 1305705 TI - Galactokinase activity in patients with idiopathic presenile and senile cataract. AB - The activity of galactokinase in red blood cells of 30 patients affected by idiophatic presenile and senile cataract, and of 20 age-matched controls with perfectly transparent lenses, was investigated. The results obtained show a partial deficiency of the galactokinase activity in the patients affected by presenile idiopathic cataract. There is, moreover, a significant relationship between the cortical form of cataract and enzymatic reduction. PMID- 1305706 TI - Trilateral retinoblastoma. AB - Retinoblastoma is the most common intraocular malignancy of childhood. Trilateral retinoblastoma is a syndrome characterized by bilateral ocular retinoblastoma in conjunction with an intracranial neuroblastic neoplasm in the pineal body, or in supraseller or parasellar location. We report the case of a three year old girl with trilateral retinoblastoma and review the literature on this subject. PMID- 1305707 TI - Pars plana versus limbal lensectomy in soft cataract. AB - With the use of automated vitrectomy instruments a new dimension has been added to the treatment of soft cataracts. Surgical approach through the limbus and pars plicata has been described previously. This work is to compare the results of both surgical techniques. Twenty eyes of soft cataract underwent lensectomy and vitrectomy using the vitrophage. Pars plana approach was applied to 10 eyes, while limbal approach was applied to the rest of the cases. No major preoperative or postoperative complication were encountered in both techniques in a follow up period up to 12 months. However, pars plana lensectomy and vitrectomy offers many advantages over the limbal one with minimal complications. PMID- 1305708 TI - Hemicentral and hemispheric retinal vein occlusions. AB - Since some authors have considered useless a differentiation between hemicentral retinal vein occlusion (HCRVO) and hemispheric retinal vein occlusion (HSRVO), we have conducted a prospective research in order to evaluate the clinical and prognostic features of these diseases. We have followed prospectively 26 cases of HCRVO and 25 cases of HSRVO. The most important risk factors were hypertension, diabetes mellitus and glaucoma in HCRVO, and hypertension in HSRVO. In the HCRVO group 20 cases (76.9%) were of the non-ischemic type and six cases (23.1%) were ischemic-type, whereas in the HSRVO seven (28%) were non-ischemic type and 18 cases (72%) were ischemic-type. Our results demonstrate that the two retinal vein occlusions are quite different with regards to pathogenesis, clinical evolution and visual outcome and point out the necessity to achieve a precise diagnosis. PMID- 1305709 TI - [Analysis of early and late results of progressive Graves-Basedow ophthalmopathy treatment with different methods]. AB - The early (immediately after the end of treatment) and late (from 12 to 91, mean 46.3 months after the end of treatment) results of progressive Graves-Basedow ophthalmopathy treatment were evaluated in 71 patients (57 women and 14 men, aged 25-66, mean 47.3 years). In all patients the thorough ophthalmological evaluation was performed early and late after treatment and the abnormalities found were classified according to Werner's method and Donaldson's ophthalmopathy index. The patients were divided into 7 groups according to different methods of treatment. Groups I-V consisted of 31 patients treated with glucocorticoids or glucocorticoids with azathioprine (Imuran) in the first stage of medication (30 patients). Plasmapheresis (7 patients) or tele-cobalt irradiation (3 patients) was applied as the second stage of treatment when the first stage was ineffective. In one person plasmapheresis and tele-cobalt irradiation was applied without previous glucocorticoid therapy. Two patients were treated successively by glucocorticoids, plasmapheresis and tele-cobalt irradiation. Very good and good late results of treatment were found in 95% of patients out of 22 reexamined persons of groups 1-5. Group 6 consisted of 7 patients treated with cobalt irradiation alone, in all 6 patients evaluated late results were good or very good. Out of 33 patients of group 7 treated by combination of glucocorticoids and telecobalt irradiation 23 were evaluated late and the results were found good or very good in 96%. The results suggest that combined treatment of progressive endocrine ophthalmopathy with glucocorticoids and cobalt irradiation is the most effective method of treatment at present. The affectivity of stage treatment is comparable with combined treatment but lasts longer and usually is more expansive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305710 TI - [Arterial hypertension associated with hyper and hypothyroidism]. AB - 45 patients with hyper and hypothyroidism in the time 1989-1990 were observed. The Graves' disease was diagnosed in 29 and rather in the younger patients, but 16 had the toxic nodular goiter and those were elderly. In 27 the hypertension was secondary (symptomatic) and after the successful treatment of the hyperthyroidism was completely controlled. In 14 cases the hypertension was primary (essential) and the application of the hypotensive drugs was also necessary. Among 4 patients with primary hypothyroidism and associated hypertension and coronary insufficiency the early treatment by the thyroid preparation was successful: the blood pressure was lowered and the coronary insufficiency was improved; but if the replacement therapy was stopped and the hypothyroidism was relapsed, the blood pressure was increases and the coronary insufficiency was aggravated. CONCLUSIONS: 1. The secondary (symptomatic) hypertension associated with the hyperthyroidism may be controlled by successful treatment of the thyrotoxicosis, but the primary (essential) must be treated by the hypotensive drugs also. 2. The early treatment of the hypothyroidism may control the associated hypertension and the coronary insufficiency. 3. Graves' disease is associated mostly with symptomatic hypertension, in nodular toxic goiter in most of the cases the essential hypertension was established. PMID- 1305711 TI - [Humoral indices of the inflammatory process in psoriasis]. AB - Immune complexes were determined in 104 patients with psoriasis, aged between 19 and 55 years. Duration of the disease, extension of lesions, and effects of infections preceding skin eruptions were considered. The studies showed the activation of immunological mechanism in psoriasis manifested by the increase in IgG and IgA levels, unchanged IgM levels, significantly more frequent negative values of IgD, significant increase in complement C4 component levels in all forms of the disease, and C3 activation in the acute and generalized chronic form. A significant increase in alpha 2 Mg was noted independently of the evolution and extension of skin lesions. An increase in alpha 1 AT was noted only in the initial phase of skin eruptions. An increase in Hp, Cr, CRP, and CIC was noted only during exacerbations. CIC were noted most frequently in postinfection psoriasis. PMID- 1305712 TI - [Use of estrogens in skin patches in treatment of pre-menstrual syndrome]. AB - A consequence of the diminishing the normal functioning of ovaries is progressing decrease in the levels of sex steroids leading to the clinical symptoms termed menopausal syndrome. This study aimed at evaluating the efficiency of Estraderm TTS-50 (Ciba-Geigy) in the treatment of this syndrome. The study involved 33 female patients, aged between 30 and 65 years. Estraderm in the form of patches containing 0.004 g of 17-estradiol was administered for 3 weeks every month, for 9 weeks. Kupperman's index, cytohormonal tests, and blood serum FSH and LH were tested before, during and after the treatment. A diminishing of the most common symptoms manifested by a statistically significant decrease in Kupperman's index and FSH, and LH levels with significant increase in serum estradiol was noted in 75% of patients following a 9-week treatment with Estraderm. Changes in the sex steroids levels led to a marked increase in the percentage of superficial cells, assessed with cytohormonal tests. Transdermal administration of estrogens in the form of Estraderm TTS-50 is the treatment of choice in the menopausal syndrome. PMID- 1305713 TI - [Familial hypoadrenalism]. AB - Congenital hypoadrenalism was diagnosed in a 18-month boy. It is suspected that hypoplasia of the adrenals is determined genetically due to the similar course and the results of autopsy in his deceased sister. PMID- 1305714 TI - [Advances in erythropoietin studies]. PMID- 1305715 TI - [Melatonin]. PMID- 1305716 TI - [The possibility of replacing blood serum with sputum for monitoring of therapy with lithium carbonate]. AB - Lithium concentration was determined in both sputum and blood serum of 31 patients treated with lithium carbonate. It was found that lithium concentration rate in the sputum/blood serum is 2.17 +/- 0.16, and is constant in all patients, except one, for a long time. A high correlation index between lithium concentration in the sputum and blood serum (r = 0.9025, and without two assays in the above mentioned patient r = 0.9858) as well as stability of sputum/serum lithium levels enable -- in the opinion of the authors -- to control lithium concentration in the body, using sputum for the assays. These assays are easy to perform with the aid of the kit called "Salivette" (Sarstedt, Germany). Its principle was discussed, too. PMID- 1305717 TI - [Effect of immuno-regulators on the function of the endocrine system]. PMID- 1305719 TI - [Prolactinoma: clinical course and biochemical changes]. PMID- 1305718 TI - [Growth hormone concentration following various factors stimulating its release]. AB - Growth hormone concentration has been assayed in 105 children (45 girls and 60 boys) during starvation and following its stimulation with clonidine and insulin and during the sleep. A significant difference between growth hormone concentration during fasting and after stimulation has been noted. No statistically significant difference between growth hormone concentrations during the sleep and following insulin has been found. The most intensive growth hormone release has been observed during the sleep. Test with clonidine is technically simple and may be performed also in the out-patient clinics. PMID- 1305720 TI - [Metabolism of plasma lipoproteins]. PMID- 1305721 TI - [Cholesterol and its lipoprotein fraction in serum and bile of patients with cholelithiasis]. AB - Total cholesterol, HDL, LDL and triglycerides were assayed in the blood serum and bile from the liver and gallbladder of both normal individuals and patients with cholelithiasis. It was found that all assayed parameters are significantly higher in patients with cholelithiasis. An increase in total cholesterol and HDL was seen in the bile from the liver whereas an increase in the level of unstable LDL by about four fold with simultaneous decrease in HDL level were found in the bile from the gallbladder. These differences in lipoprotein fractions level in patients with cholelithiasis indicate systemic disorders in cholesterol metabolism. PMID- 1305722 TI - [Blood pressure and blood lipids in normotensive patients with diabetes mellitus type I with microalbuminuria]. AB - The study involved 50 normotensive men (means age = 34 years) with diabetes mellitus type I (mean duration of the disease 14 years). Group I included 29 patients with normal albumin excretion with the urine (UAE below 30 mg daily), and group II-21 patients with microalbuminuria (UAE 30-300 mg daily). Both groups were similar in relation to the age and duration of diabetes mellitus. Blood cholesterol was significantly higher in patients of group II than in patients of group I (p = 0.02) similarly to blood triglycerides levels (p = 0.01). Mean arterial pressure was lower in patients of group I than that in patients of group II (94.3 +/- 7.0 vs 99.1 +/- 6.0 mm Hg; p = 0.01). HbA1c was positively correlated with blood cholesterol (p = 0.01) and blood triglycerides levels (p = 0.05). PMID- 1305723 TI - [Effect of 5-month guanfacine treatment on the renin-angiotensin-aldosterone system and some metabolic factors in patients with diabetes mellitus type II and hypertension]. AB - The group of the investigated included 25 individuals (11 F, 14 M), aged 55 +/- 1.5 years, with diabetes type II and hypertension. Known diabetes duration was 4.9 +/- 0.8 years and known hypertension duration--7.4 +/- 1.4 years. Two weeks after administering placebo in place of hypertension drugs applied so far, guanfacine was included as the only hypertensive drug. The dosage was increased from 0.5 mg up to 3 mg daily until a good control of blood pressure was achieved. The diabetic treatment, diet and the smoking habit were unchanged. The resting activity of the renin-angiotension-aldosterone system (RAA), cholesterol, triglycerides, HDL and LDL, serum glucose levels and HbA1c were assayed after a 5 month guanfacine period. After treatment a significant decrease in blood pressure both systolic and diastolic (p < 0.001), heart rate (p < 0.005) and plasma renin activity (p < 0.02) were observed. Preliminary measurements of RAA activity and its changes during treatment were not helpful in predicting guanfacine hypotensive effect. The level of lipids, lipoproteins, atherogenic factors, glucose and HbA1c did not change significantly during the study. PMID- 1305725 TI - [Primary hyperlipoproteinemia type V]. PMID- 1305724 TI - [Effect of compositional modification of coffee on certain indices of lipid metabolism in healthy volunteers and patients with hyperlipoproteinemia]. AB - An effect of a 14-day drinking of coffee on some blood serum indices of lipid metabolism was investigated in 20 healthy volunteers and 20 patients with hyper lipoproteinemia (type IIb). The study was carried out in two subgroups: healthy volunteers or patients with hyperlipoproteinemia assigned to the first subgroup drank ordinary coffee and patients assigned to the second subgroup drank coffee deprived of irritant substances (4 glasses daily). It was found that ordinary coffee significantly increased total serum cholesterol and decreased serum HDL cholesterol in healthy volunteers. Such effects were not seen in subgroup drinking coffee deprived of irritant substances. More significant increase in serum total cholesterol and decrease in serum HDL-cholesterol were found in patients with hyperlipoproteinemia. Drinking of modified coffee does not cause any significant changes in serum lipid metabolism. The authors concluded that drinking of the ordinary coffee should be restricted in patients with hyperlipoproteinemia and use of coffee deprived of irritant substances might be recommended to patients with this disease. PMID- 1305726 TI - [Physiologic regulation of insulin release]. PMID- 1305727 TI - [Pyomyositis of skeletal muscle]. PMID- 1305728 TI - [Receptors for natriuretic peptides]. PMID- 1305729 TI - [Circadian changes in levels of magnesium in serum of healthy individuals]. AB - Circadian changes in blood serum magnesium levels in healthy individuals. We examined circadian changes of the serum magnesium in 20 healthy subjects. Blood samples were taken every second hour during the 24 hours. Male serum magnesium concentrations increased from the lowest level (0.810 +/- 0.035 mmol/l) observed at 8.00 am to the highest level (1.028 +/- 0.084 mmol/l) at 6.00 pm. Female-we observed two peaks of serum magnesium concentrations: first at 8.00 pm (0.992 +/- 0.103 mmol/l) and second at 4.00 am. (0.982 +/- 0.094 mmol/l) with the lowest level at noon) 0.789 +/- 0.043 mmol/l. Differences between extreme levels were statistically significant. PMID- 1305730 TI - [Diagnosis of acute primary abdominal diseases in patients treated with continuous peritoneal dialysis]. PMID- 1305731 TI - [Estimation of hearing in patients with end stage renal failure being peritoneally dialyzed with and without furosemide in the dialysis fluid]. AB - The purpose of our study was to estimate hearing state and effect of intraperitoneal administration of furosemide on an organ of hearing in the patients with end-stage renal failure being treated with intermittent peritoneal dialysis. Ten patients divided into two groups, were observed for three months. A weekly dosage of 1.2-2.0 g of furosemide was administered to the patients of first group while the patients of second group were not given furosemide. Based upon the studies, which had been carried out by pure tone audiometry method and Fowler's test and Belesy's audiometry, it was found the lesion of hearing, mainly in the range of higher frequency, having a character of cochlear hypoacusia. The further lesion of hearing was not seen within three months of regular treatment with intermittent peritoneal dialysis. The audiometric studies which had been carried out in different stages of treatment, did not show ototoxicity influence of furosemide added to dialysis fluid. PMID- 1305732 TI - [Effect of ACE inhibitors on proteinuria and renal functioning in primary glomerulopathies]. AB - Angiotensin converting enzyme inhibitors was given to 16 patients with glomerular nephritis in whom a complete remission of nephrotic syndrome could not be achieved with immunosuppressive-anti-inflammatory therapy. Captopril in the daily dose of 25-75 mg and enalapril in the daily dose of 10 mg were administered for 1 36 months (mean 12.6 months). Daily proteinuria decreased by 40-80% comparing with baseline value in 2/3 of patients. Total protein and albumin serum levels increased simultaneously. No changes in blood creatinine were noted in patients with initially normal renal functioning except one patient. Renal functioning was stable in 50% of patients with increased blood creatinine levels (mean 200 mumol/L). Blood creatinine was increasing in the remaining patients. PMID- 1305733 TI - [Clinical estimation of 1-alpha-hydroxycholecalciferol in treatment of patients with chronic renal failure]. AB - 31 adult patients (15 male and 16 female) with chronic renal failure were treated for 6 months with 1-alfa-hydroxycholecalciferol on a dose 0.25-2.0 micrograms/24 h. 15 patients with not very advanced renal failure (serum creatinine level 176.8 442 mumol/l) received conservative therapy (group I), 16 patients with serum creatinine value 884-1326 mumol/l were treated by intermittent hemodialysis (group II). The statistically significant decrease of serum alkaline phosphatase activity in group I and II (p < 0.01), the rise of serum calcium level in group I (p < 0.005) were determined. Half of the patients from both the groups stated the relief or disappearance of bone and joint pains and muscle weakness. Besides in group I significant decrease of creatinine clearance (p < 0.001) and increase of serum urea and creatinine value (p < 0.01) were noticed. On the basis of these results we can conclude that the treatment with 1-alfa-hydroxycholecalciferol, produced by "Polfa", ought to be introduced gradually with increasing doses and frequent monitoring of calcium-phosphate metabolism and renal function parameters. PMID- 1305734 TI - [Usefulness of computed tomography for diagnostic differentiation of complications after renal transplantation]. AB - This paper demonstrates the usefulness of Computer Tomography (CT) for diagnosing the commonest complications after kidney transplantation. It was pointed out that CT is particularly helpful in detection and differentiation of perirenal fluids as well as in diagnosing of kidney rupture. PMID- 1305735 TI - [Comparison of treatment outcome in patients with rheumatoid arthritis treated with TFX- Polfa or gold salts after a one year follow up]. AB - Thirty five patients with rheumatoid arthritis were given TFX Polfa, initially everyday in the intramuscular injections in the dose of 10 mg TFX protein for 60 days, followed by 1 injection of 10 mg TFX protein a week for 10 months. Other 30 patients with rheumatoid arthritis treated with gold salts were used for comparison. Several clinical and laboratory tests were performed before the treatment and after 1 year. A one-year therapy significantly improved all clinical parameters in both groups. A significant increase in hemoglobin and erythrocyte count was noted in patients treated with TFX. A significant decrease in the markers of inflammation was seen. A percentage of both early and delayed E rosettes increased highly significantly. The obtained results suggest that TFX Polfa is efficient in these cases of the rheumatoid arthritis which cannot be treated with gold salts. PMID- 1305736 TI - [Pefloxacin in the treatment of chronic urinary infection]. AB - This study aimed at determining sensitivity of the hospital isolates to pefloxacin compared with other urinary antiseptics and assessment of its efficiency in the treatment of the chronic urinary infections. Disc diffusion technique was used to determine bacterial sensitivity to pefloxacin and other agents. Bacteria were isolated from the urine of the hospitalized patients. All tested strains were sensitive to pefloxacin. Its sensitivity exceeded in vitro 80%. Fifteen patients full sensitive to pefloxacin were treated. No bacteria were seen in the urine of 8 patients in two bacteriological cultures following the treatment, 3 patients stopped therapy due to adverse reactions, and no sterile urine was noted in 4 patients despite following a complete cycle of therapy. PMID- 1305737 TI - [The effect of hypotensive nifedipine therapy on renal secretory function in hypertensive patients in the course of both compensated and non-compensated chronic renal failure]. PMID- 1305738 TI - [Arterio-venous fistula of the Brescii type as a cause of circulatory failure in hemodialysed and dialysed patients with chronic renal failure]. PMID- 1305739 TI - [Reversible renal failure in female patients with acute interstitial nephritis caused by cloxacillin]. AB - Cloxacillin was not listed as one of the drugs causing the acute interstitial nephritis, yet. A case of a 50-year female patient treated with cloxacillin is presented. Therapy was followed by nausea, vomiting, myalgia and arthralgia, and the symptoms of the acute renal failure which completely diminished after prednisone therapy despite of co-existing peptic ulcer. Low doses of corticosteroids seem helpful in the treatment of the acute interstitial nephritis following therapy with cloxacillin even after a long time of the onset. PMID- 1305740 TI - [Effect of calcium channel blockers and angiotensin I converting enzyme inhibitors on the kidney]. PMID- 1305741 TI - [Carnitine in patients with renal failure subjected to chronic dialysis therapy]. PMID- 1305742 TI - [Otitis media in children smoking tobacco]. PMID- 1305743 TI - [Baby Jesus Hospital during the Warsaw uprising]. PMID- 1305744 TI - A difficult case of angina. PMID- 1305745 TI - Jaundice--the first 48 hours. PMID- 1305746 TI - Screening elderly patients. PMID- 1305747 TI - Child autonomy. PMID- 1305748 TI - New horizons. PMID- 1305749 TI - Late-onset asthma. PMID- 1305750 TI - Communication and education. PMID- 1305751 TI - Osteoarthritis. PMID- 1305752 TI - Soft tissue injuries. PMID- 1305753 TI - Rheumatoid arthritis. PMID- 1305754 TI - Backache in general practice. PMID- 1305755 TI - Slow-release delivery systems. PMID- 1305756 TI - The patient's interests need safeguarding. PMID- 1305757 TI - The prescriber must have full responsibility. PMID- 1305758 TI - Uncontrolled asthma. PMID- 1305759 TI - Surgery for cataracts. PMID- 1305760 TI - Developing professionalism. PMID- 1305761 TI - Health promotion for young people. PMID- 1305762 TI - Drug misuse in adolescence. PMID- 1305763 TI - Psychiatric disturbance. PMID- 1305764 TI - Sexually transmitted diseases. PMID- 1305765 TI - Using controlled-release preparations. PMID- 1305766 TI - An effective 'cure' for a chronic disease. PMID- 1305767 TI - Reserve eradication therapy for selected patients. PMID- 1305768 TI - Relationship between cardiovascular functions and ionic hypocalcemia induced by citrate infusion in anhepatic swines: CaCl2 therapy in severe ionic hypocalcemia. AB - Baseline and serial values of serum [Ca++], [K+], [Na+], arterial blood gas tensions, acid-base status, temperature and hemodynamic functions were measured during infusion of citrate-phosphate-dextrose (CPD) solution (0.35 ml.kg-1 x min 1) in anhepatic pigs of three randomized groups. Thirteen pigs (group I) continued to receive intravenous infusion of CPD solution until cardiac arrest. When mean arterial pressure (MAP) decreased to about 50 mmHg (group II, n = 7), or 40 mmHg (group III, n = 7) infusion of CPD solution was discontinued, and pigs received CaCl2 (20 mg/kg) intravenously. Serial (1, 4, 8, and 12 min after CaCl2 administration) values of all the above variables and serum citrate at baseline and lowest [Ca++] were measured. After hepatectomy and venovenous bypass, cardiac output (CO) decreased 30%. When ionic hypocalcemia was above 0.7 mM, there was no significant change of cardiovascular functions. When [Ca++] was between 0.34-0.7 mM, there were linear relationships between [Ca++] and CO, systemic vascular resistance (SVR) and MAP, respectively. When [Ca++] was below 0.34 mM, cardiovascular functions decreased abruptly, and the pigs died at [Ca++] of 0.26 +/- 0.06 mM. When [Ca++] decreased to 0.36 +/- 0.06 mM and MAP to 50 +/- 4 mmHg, most hemodynamic functions could be reversed by calcium therapy. However, when [Ca++] decreased to 0.33 +/- 0.05 mM and MAP to 40 +/- 2 mmHg, hemodynamic functions could not be reversed by calcium therapy alone. PMID- 1305769 TI - Effects of toluene on the morphology of neuropeptide secretory neurons of the rat hypothalamus. AB - The effect of toluene on the hypothalamic hormone-secreting neurons and neurotransmitter-containing fibers in the rat was investigated by immunohistochemical methods. Multiple intraperitoneal injections of toluene (totally 7.5 ml) led to significant decreases of the neuronal numbers of vasopressin, oxytocin and neuropeptide Y in the preoptic and hypothalamic areas. The densities of vasopressin, oxytocin, norepinephrine and neuropeptide Y immunoreactive fibers of the toluene dose group decreased markedly in the median eminence. In contrast, LHRH neurons remained unchanged. PMID- 1305770 TI - High resolution electron microscopic investigation of atomic structural images in human atherosclerotic plaque. AB - Atomic structural images in the calcified matrix of human atherosclerotic plaques were characterized by high-resolution electron microscopy (HREM). The mineral elements distributed in the calcified matrix were analysed by energy dispersive X ray microanalysis. Careful HREM observations revealed that a large number of microcrystallites and crystal particles with a broad spectrum of crystal size and perfection were embedded in the amorphous matrix of the calcified plaques. The amorphous phase in the calcified matrix was made up of a dense network of granulo fibrillar substructures. The lattice-fringes with regular arrangement of atom columns along the lattice arrays were clearly demonstrated in the crystalline particles of the calcified plaques. A number of characteristic granulo-fibrillar substructures in the amorphous phase could be seen to be tightly connected to the lattice-fringes in the crystalline phase along the interfaces between the amorphous and crystalline phases. The crystal lattices at the boundary between two crystals were very well matched with the periodicity of visible atoms continuous through the two crystals. The mineral elements such as calcium and phosphorus were detected to be diffusely distributed in the calcified matrix of the atherosclerotic plaques. Based on these findings, it is concluded that: (1) an interlacing network of granulo-fibrillar substructures in the amorphous matrix may play a structural and/or regulatory role for the organic matrix by providing sites for nucleation; and (2) the deposition of the mineral elements may be effective for the transformation of the amorphous nucleation phase to well crystallized nucleation phase. PMID- 1305771 TI - Analysis of ragweed allergens recognized by monoclonal antibody 8-5 using two dimensional gel electrophoresis and immunoblotting. AB - A series of MoAbs against major allergens (Amb a I and Amb a II) of the short ragweed pollen is reported by this laboratory. One of these MoAbs, 8-5, showed strong reactivity to Amb a II, weak reactivity to Amb a I-B and I-C, and no reactivity to Amb a I-B2 of the short ragweed pollen by SDS-PAGE and immunoblotting. In the present study, ragweed allergens recognized by MoAb 8-5 were further analyzed by two-dimensional gel electrophoresis and immunoblotting. The results showed that MoAb 36-6, which has been identified to be reactive with Amb a I only, reacted mainly with components with MW of about 39 kD, which corresponded to creatine kinase charge standards from -14 to -20 in both the Amb a I-B and I-C preparation and the crude extract of the short ragweed pollen. However, MoAb 8-5 showed strong reactivity to components with about the same MW but charge standards from -8 to -13 in Amb a II and the crude extract of the short ragweed pollen. Furthermore, a weak positive reactivity of MoAb 8-5 to components with MW of about 39 kD and charge standards from -8 to -14 in Amb a I B and I-C was also observed. It was thus concluded that MoAb 8-5 reacted with Amb a II only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305773 TI - [Safety assessment of rabies vaccine strains used for oral wild animal immunization]. PMID- 1305772 TI - Production of cephalexin by Gluconobacter oxydans CCRC 10383. AB - Intact cells of Gluconobacter oxydans CCRC 10383 produced cephalexin from 7-amino 3-deacetoxy cephalosporanic acid (7-ADCA) and D-alpha-phenylglycine methylester HC1 (PGM). Factors affecting the production of cephalexin by G. oxydans CCRC 10383 were studied. The optimum pH and temperature for the synthetic reaction of cephalexin were 6.0 and 42 degrees C, respectively. A higher concentration of PGM than 7-ADCA was required to obtain a good yield of cephalexin. PMID- 1305774 TI - [The comparison of dynamics in humoral responses in health personnel after vaccination against hepatitis B using Engerix B and Gen-H-B-vax]. AB - The dynamics of humoral response in two groups of health care workers vaccinated according to the schedule 0, 1, 6 months, using two different recombinant vaccines has been comprised. In the group of persons vaccinated with Engerix B, 63 completed the full cycle of vaccination. Protective titer of anti-HBs (> or = 10 IU/L) was obtained in 93.6% of vaccinated. In the group of persons vaccinated with Gen-H-B-Vax, 62 completed the full cycle of vaccination, and protective titer of anti-HBs amounted to 90.3% of vaccinated. The humoral response on the protective level in both groups was not statistically different. However, the percentage of the persons with very high anti-HBs titers (10,000 and more IU/L) was higher after Engerix B. PMID- 1305775 TI - [Long term results of vaccination against viral hepatitis B using recombinant vaccine Engerix B]. AB - Among nineteen persons vaccinated against hepatitis B (recombinant Engerix B vaccine) fifteen (80 per cent) have developed anti-HBs (investigated 30 days after the third doses) on the protective level (10 U/l). After three and a half year three of them lost antibodies, and four had anti-HBs at level below 100 U/l. All of them received a booster doses, which resulted in a very high anti-HBs level one month later. Four persons without anti-HBs after the basic vaccination received in turn two booster doses: at the 3rd and 46th month. Only one person of them have remained a non-responder. We suggest to control a level of anti-HBs one month after basic vaccination for individual determination of the term of booster dose. PMID- 1305776 TI - [Familial incidence of hepatitis b]. AB - Among 693 patients treated in our Hospital with HBV, we separated 88 persons from 34 familial focuses. In those separated cases the most likely way of transmission were the familial contacts, without data indicating the other sources of infection (surgery, blood transfusions). The most common source of infection were children. We postulate vaccination of the HBsAg(-) person, staying in the familial contact with HBV patients. PMID- 1305777 TI - [Analysis of the epidemiologic situation of hepatitis B among children in the Kielce province 1986-1991]. PMID- 1305778 TI - [The course of acute HCV infection in patients with chronic non-A, non-B hepatitis]. AB - Among 52 patients with chronic non-A, non-B hepatitis, observed for many years in the Department of Infectious Diseases of Pomeranian Medical Academy, retrospectively diagnosed towards HCV infection, 45 proved to be anti-HCV positive. Sera stored in the bank of sera were examined using 2nd generation tests: ABBOTT HCV EIA (Abbott), ORTHO RIBA (Ortho Diagnostics) and UBI HCV EIA (Organon), showing 85% of positivity. Mostly HCV infection was connected with the blood transfusion. The course of acute phase of HCV infection was mild, short lasting, with no or sporadic extrahepatic symptoms; the activity of aminotransferases and the bilirubin level were of average value. The only characteristic feature of the acute HCV infection was fluctuating aminotransferase activity, which can be the good sign of progression. PMID- 1305779 TI - [Analysis of the correlation between measles and subacute sclerosis panencephalitis (SSPE) before and after introduction of vaccination in Poland]. AB - Number of SSPE cases were analysed depending on epidemiologic situation of measles in Poland. Statistic analysis exhibit significant correlation between measles incidence in first year of live and total number of SSPE cases born in the same years. Problems antimeasles vaccination for eradication measles and SSPE were discussed based on the correlation. PMID- 1305780 TI - [Epidemiology of influenza and characteristic etiological factors in the 1990/91 season]. PMID- 1305782 TI - [Endemic occurrence of lyme disease in the forested areas of the Pila district]. AB - Lyme disease (L.D.) caused by Borrelia burgdorferi and spread by Ixodes ticks arouses great interest with more and more clinicians and other scientists. It may be very difficult to diagnose a disease as L.D. because of its various clinical symptoms expressions. This is why it is often called "the great imitator". There are three phases in the natural history of the disease. Diagnostic problems come from the fact that early phases are often lacking. The disease may begin with any symptom of any stage. In our paper we present the endemicity of Lyme disease among a group of 28 people who spent their summer holidays on a forest camp near Pila (in the north-western part of Poland) in July 1991. We diagnosed 15 of them as having early stages of L.D. PMID- 1305781 TI - [Serologic surveillance of influenza during the epidemic season 1990/91 in Poland]. AB - The level of antibodies was tested in 9 age groups since 6 years up to over 75 years of age for H and N of influenza A(H1N1), A(H3N2) and B in epidemic season 1990/91. The highest GMT were found in all age groups for H3-A/Shanghai/16/88, much lower for H1-A/Taiwan/1/86. The titers were almost the same in all age groups excluding 6-8 years where GMT was much higher. The lowest titers were found for hemagglutinin of B/Yamagata/16/88 and different in different age groups. The highest GMT of neuraminidase were found for N2 in group 41-50 years old, in other groups were different. GMT for N1 were differentiated, but in 51-64 years old group was 3.5 times higher in comparing to the lowest value. For B neuraminidase the titer of antibodies was the highest in 31-40 years old group, and the lowest for 41-50 old people. PMID- 1305784 TI - [Evaluation of safety and immunogenicity of the Td vaccine in laboratory studies]. AB - The new vaccine recommended as the booster dose contains in 0.5 ml: 10 BU Te toxoid, 2 Lf Di-toxoid, 4.5-0.5 mg Al and 0.01% merthiolate. In 7 consecutive series it was state, the vaccine was safety and stable. The potency was 40-50 JO for Te and 30-40 for Di. The last series was recommended for vaccination under clinical control. PMID- 1305783 TI - [Isolation of Clostridium perfringens from a wound in a case of post-traumatic gas gangrene. Diagnostics remarks]. AB - The authors described a case of post traumatic gas gangrene in a young man. Rapid clinical and microbiological diagnosis with isolation of Clostridium strain, and immediate therapy, including hyperbaric chamber, brought complete recovery without incapacitation. PMID- 1305785 TI - [Evaluation of vaccination reactions and serologic responses after Td vaccine in pilot studies]. AB - Fifty six young adults volunteers received 10 BU tetanus and 2 Lf Diphtheria adsorbed vaccine (Td). Reactogenicity was noted in the special formulas, the serological response was determined by the passive hemagglutination in sera collected before and in 4 week after the vaccination. Twelve persons were not immunity for diphtheria before booster. The results confirmed the safety and efficacy of the polish Td vaccine. PMID- 1305786 TI - [Elaboration and examination of the functioning of a new system for collection and analysis of information on foodborne and waterborne diseases in Poland]. AB - During 1986-1989 the new computerized system of collection and analysis of foodborne and waterborne infections and intoxications (based on the proposition of World Health Organization) was developed in the Department of Epidemiology of the National Institute of Hygiene in Warsaw. System consists of the new forms (including computer's form) and adapted original programming. The new forms were officially introduced by the Ministry of Health and Welfare for the use by the all Sanitary Stations in Poland from the beginning of 1991. That system was served to present data on epidemiological situation of foodborne and waterborne infections and intoxications in Poland in 1988-1991, demonstrated in the paper. Criteria of analysis were adapted to meet conditions of the international cooperation, and-first of all-to the requirements of Polish epidemiological situation. PMID- 1305787 TI - [Infant mortality and perinatal mortality in Poland in the eighties]. AB - The dynamics of the changes in the level of infant mortality and perinatal mortality in Poland during 1980-89 by age and cause is presented. The statistical definitions concerning the perinatal period are used according to the World Health Organization's recommendations. There is stronger decline in postneonatal mortality rates then in neonatal rates during the eighties. The level of neonatal mortality rates (14.8 in 1989) and perinatal mortality rates (19.6 in 1989) is high comparing to the developed countries. PMID- 1305788 TI - [Upper respiratory tract infections as a hypothetical source of sudden infant death syndrome (SIDS)]. AB - A hypothesis that the common bacterial toxins are the possible cause of the Sudden Infant Death Syndrome (SIDS) was discussed. Recently, even botulinum toxin and Clostridium perfringens Type A enterotoxin are mentioned. PMID- 1305789 TI - [Tobacco smoking and alcohol consumption as risk factors for stomach cancer in different locations and histologic types]. AB - A multicancer hospital based case-control study involving interviews with 741 incident male and female gastric cancer cases under the age of 75 years and an equal number of age and sex matched controls has been carried out in Poland. Smoking cigarettes without filter increased the risk for intestinal cancer in the cardia part of the stomach (OR = 3.72, 95% CI: 1.35-10.23). Relative risk of the intestinal type of cancer in the distal part of the stomach was augmented with the increasing frequency and amount of vodka drinking. Subjects who drank vodka at least once a week had about 4.5 times the risk of intestinal cancer of the gastric corpus compared to non-drinkers (RR = 4.45, CI: 2.26-8.75). The relative risk of intestinal carcinoma in the distal stomach due to vodka drinking among those who used to drink vodka on an empty stomach was also elevated (RR = 3.28, CI: 1.33-8.13), but the effect of years of vodka drinking habit failed to show significant association with gastric cancer. A weak interaction effect between smoking and vodka drinking was found for intestinal cardia cancer. Diffuse type gastric carcinoma or mixed type carcinoma were not significantly related to smoking or vodka drinking habits. PMID- 1305790 TI - [Remarks about studies on geographic distribution of malignant neoplasms]. PMID- 1305791 TI - [Iron deficiency and anemia in professional working women]. AB - The hematological indices (Hb, Ht, MCHC) and iron status (serum iron, TIBC, LIBC, transferrin saturation), the prevalence of iron deficiency anemia in 224 women aged 31 to 47 years, working in textile industry in Lodz were examined. Nutritional status was evaluated as follow: body height and weight, body mass index (BMI kg/m2) and body fat content (%) calculated from the four skinfolds sum. Anemia (Hb < 12 g/dl) was stated in 11.2% participating women, evident iron deficiency (Fes < 60 micrograms/dl, Sat % < 16) in 13.4% of population. The positive correlation was found among hematological indices and body weight, body mass index and body fat content and relationships among iron status indices (Fes mu/dl, Sat%-positive correlation; TIBC microgram/dl, LIBC microgram/dl-negative relationship) and body fat content (%). The prevalence of iron deficiency and anemia were lower than in other women population in Poland examined in 1974-1986. The relationships among energy and protein nutrition and iron status and iron deficiency anemia suggest, that the menstruating overweight women or with obesity may be the group with lower risk of iron deficiency anemia. PMID- 1305792 TI - Description of Dogielius molnari n. sp. (Monogenea: Dactylogyridae) from the gills of an Iranian freshwater fish, Cyprinion macrostomum (Heckel). AB - The occurrence of a new Dogielius species is reported from the gills of Cyprinion macrostomum (Cyprinidae), an endemic fish of the River Tigris water system. The species is described as Dogielius molnari n. sp. PMID- 1305793 TI - Effect of acute salinomycin-tiamulin toxicity on the lipid peroxide and antioxidant status of broiler chicken. AB - The combined effect, if any, of salinomycin poisoning and salinomycin-tiamulin interaction on lipid-peroxidative processes and the antioxidative defence system of the liver was studied in domestic fowl. Male broilers (28-day-old), reared on a diet containing 60 mg/kg salinomycin, were treated intraoesophageally with salinomycin (140 mg/kg body mass) or tiamulin (50 mg/kg body mass). Malondialdehyde, reduced glutathione and cytochrome P-450 concentrations as well as glutathione peroxidase and catalase activities of the liver were determined. Liver malondialdehyde concentration rose in the salinomycin-treated group while the amount of cytochrome P-450 increased in both groups treated. Glutathione concentration and glutathione peroxidase activity of the liver decreased rapidly but hepatic catalase activity increased in both groups after the treatment. Manifestation of the effect exerted by salinomycin and salinomycin-tiamulin on lipid-peroxidative processes nearly coincided with the onset of clinical signs and preceded the increase of hepatic cytochrome P-450 concentration. According to the results, the background of the previously reported incompatibility between salinomycin and tiamulin is the synergistic effect exerted on the antioxidant (glutathione) system. PMID- 1305794 TI - The involvement of polymorphonuclear leukocytes in the pathogenesis of bronchopneumonia in calves. VI. Superoxide dismutase and lipoprotein lipase activities. AB - The kinetics of superoxide anion production in polymorphonuclear leukocytes of bronchopneumonic calves, as well as superoxide dismutase and lipoprotein lipase activities in the blood plasma of these animals were studied. Granulocytes of bronchopneumonic calves were found to produce 10 times as much O2- radicals as those of healthy animals. Superoxide dismutase and lipoprotein lipase activities were lower in the plasma of bronchopneumonic calves. Escherichia coli endotoxin was found to stimulate superoxide anion production in polymorphonuclear leukocytes in a dose-dependent manner. These facts suggest that an endogenous mediator, probably cachectin or some other monokine(s), plays a role in granulocyte activation during calf bronchopneumonia. PMID- 1305795 TI - The involvement of polymorphonuclear leukocytes in the pathogenesis of bronchopneumonia in calves. VII. Granulocyte activation by arachidonic acid. AB - Arachidonic acid-induced granulocyte activation was studied in calves. Both in healthy and in bronchopneumonic animals, neutrophil stimulation with 67 microM arachidonic acid caused a rise in granulocyte exocytosis. This event, however, was much more intense in granulocytes from diseased calves. Fatty acids were found to stimulate granule exocytosis from granulocytes. Oleic acid possessed the weakest while dihomo-gamma-linoleic acid showed the strongest activity of this type. It is suggested that arachidonic acid may be an important mediator of calf bronchopneumonia. PMID- 1305796 TI - Activity of serum creatine kinase, lactate dehydrogenase and LD isoenzymes in piglets affected with congenital tremor: a case report. AB - The activities of serum creatine kinase (CK), lactate dehydrogenase (LD) and LD isoenzymes were studied in 14 Prestice black pied pigs from a herd affected with congenital tremor. Mean CK activity was 19.57 +/- 3.56 mu kat.l-1 for 6 adult pigs, and it was 21.03 +/- 1.33 mu kat.l-1 and 20.42 +/- 1.23 mu kat.l-1 for the affected (n = 5) and control (n = 3) piglets, respectively. No significant differences were demonstrable between the groups in CK activity. Total serum LD and LD-4 as well as LD-5 isoenzyme activities were higher in sows. Piglets affected with congenital tremor showed an increase in total LD enzyme and LD-5 isoenzyme activity. It is concluded that no relationship exists between congenital tremor and serum CK activity in piglets. At the same time, there is a positive relationship between congenital tremor and significantly (P < 0.01) elevated LD enzyme and LD-5 isoenzyme activity. The results allow us to suggest that total lactate dehydrogenase and LD-5 isoenzyme activities could be used as biological markers of congenital tremor in piglets. PMID- 1305798 TI - Checking of immunity against Newcastle disease by ELISA. AB - A total of 284 seven- to twelve-week-old Tetra SL chickens were assigned to 18 groups and immunized with a full or fractional dose of monovalent or multivalent inactivated vaccines subcutaneously or intramuscularly. Sera were taken from the birds at the time of challenge and tested for antibodies to Newcastle disease virus (NDV) by enzyme-linked immunosorbent assay (ELISA). The vaccinated birds were challenged with 10(6) ELD50 of virulent NDV subcutaneously. A close positive correlation (r = 0.954) was found between the protection percentage of the different groups and the group's arithmetical mean net extinction percentage (NE%) calculated from the net extinction values obtained for sera of birds belonging to the given group. NE% is easy to calculate and a good indicator of the flocks' immunity status. In our case: if NE% exceeded 80, the protection percentage of the flock was between 93.3 and 100%; if NE% was between 60 and 80, the protection percentage was between 75 and 87%, while with an NE% less than 60 the protection percentage ranged between 6.7 and 64.3%. PMID- 1305797 TI - Is there lipid peroxidation induced malondialdehyde production during egg shell formation? AB - The marked increase observed in malondialdehyde concentration of the blood plasma and liver of laying hens during egg shell formation in a previous experiment (Mezes and Lencses, 1985) were explained as a possible consequence of physiologically controlled lipid peroxidation. In this experiment, 54-week-old laying hens were treated intrauterinally with indomethacin (1.0 and 2.0 mg/kg body mass) after oviposition. Two other groups of hens were treated per os with excess amounts of vitamin E (100 and 200 mg/bird). The higher dose of indomethacin significantly decreased the PGF2 alpha production and malondialdehyde content of the sell gland, as well as the malondialdehyde concentration of the plasma. The excess amount of vitamin E had the same effect. The results suggest that during egg shell formation malondialdehyde is derived from prostanoid biosynthesis rather than from a free-radical initiated lipid peroxidative process. On the other hand, the excess amount of vitamin E inhibited prostaglandin biosynthesis as well as malondialdehyde production. PMID- 1305799 TI - Pathogenic properties of Newcastle disease virus isolates in the Sudan. AB - Six Newcastle disease virus (NDV) isolates were obtained from disease outbreaks on different poultry farms in the Sudan between 1988 and 1991. The pathogenic properties of these isolates were studied in comparison to those of strain Herts 33/56. All the isolates were similar in that they killed chicken embryos quickly, in mean death time (MDT) and embryo lethal dose 50 per cent (ELD50), had higher intracerebral pathogenicity indices (ICPI), and produced viscerotropic lesions in the infected chickens. The field isolates had the characteristics of the velogenic viscerotopic strains of NDV. The pathogenesis of infection caused by one of the isolates was studied. The virus was first detected in different organs and in oral and cloacal swabs on the third day after infection. PMID- 1305800 TI - [Contribution of chemiluminescence for determination of low value TSH in patients with dysthyroidism during negative TRH test]. AB - TSH values performed by immunoradiometric method were compared with chemiluminescent method in 28 hyperthyroid patients with negative TRH-test. This last method gives a better sensitivity (0.020 mUI/L vs. 0.050 mUI/L) and reproducibility (5% V.C. vs. 40%). The measure of undetectable TSH by immunoradiometric assay becomes possible with chemiluminescence. Due to this increase of sensitivity, the TRH-test needs to be reconsidered and allows to discriminate various degrees of TSH suppression. PMID- 1305802 TI - [Acromegaly and bronchial carcinoid tumor. Apropos of a case]. AB - Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. A 29-year-old woman with acromegaly secondary to ectopic GHRH secretion by a bronchial carcinoid tumor is presented. Normalization of GHRH levels, reversal of pituitary hyperplasia and regression of acromegaly followed resection of the bronchial tumor. The authors stressed the interest of GHRH dosage in patients with acromegaly and pituitary hyperplasia. PMID- 1305801 TI - [Serum human growth hormone assay. Comparison of six assay kits]. AB - Measurements of human growth hormone (hGH) plasma levels using mono or polyclonal antibodies based on kits are often highly variable depending upon the kit used. We compared six kits commercially available: one based on polyclonal antiserum, five based on monoclonal antisera. We measured 695 sera obtained in short stature children (GH deficiency or normal GH secretory) and adults (normal, hypopituitarism or acromegaly). Our results confirm the variability between the assays. The maximal variation was obtained with SBhGH kit which showed mean results 1.7 fold higher than those obtained with hGH Coatria. Using the OMS 80.205 standard with the six kits, we found a good correlation between the six kits indicating that the standard used in each case was not responsible for the observed variations. This suggest that the different antibodies used in these kits may recognize different isoforms of circulating hGH. In addition variations in reagents used in the different kits may also explain these discrepancies. The variations observed using these six commercially available kits may have important clinical repercussion and especially may impede the diagnosis in hGH deficiency in children. PMID- 1305803 TI - [MRI exploration of the hypothalamo-hypophyseal axis]. AB - MR Imaging has become the procedure of choice for the exploration of the pituitary region. MR contrast resolution is far better than the finest CT examination, especially concerning the microadenomas and the neurohypophysis. The present paper concerns, at first the major principles of magnetic resonance imaging, its application for the study of the pituitary region including the use of contrast agent (Gadolinium). Lastly, MR anatomy and physiological variations are presented. PMID- 1305804 TI - 'Computers in dentistry'. PMID- 1305805 TI - Training in obstetrics. PMID- 1305806 TI - 'The autobiography of Dr Lilian Lindsay'. PMID- 1305807 TI - Problems in primary care. PMID- 1305809 TI - A remarkable woman: Margaret Trevitt, MD, 1858-1925. PMID- 1305808 TI - Growth hormone treatment in idiopathic short stature: a preliminary analysis of cardiovascular effects. AB - Growth hormone (GH) hypersecretion is associated with an increased incidence of hypertension and cardiac hypertrophy, resulting in excess cardiovascular morbidity and mortality. Abnormalities in the renin-angiotensin-aldosterone (RAA) system have been reported in acromegaly and in normal adults treated with recombinant human GH. The RAA system was investigated in prepubertal children with idiopathic short stature during treatment with recombinant human GH in doses up to 40 IU/m2/week. In addition, left ventricular size and function were assessed by serial echocardiography over an initial 12-month period. Modest and transient increases in blood pressure and body weight were observed during the first 7 days of GH treatment, but this was not accompanied by activation of the RAA system. Echocardiographic parameters of left ventricular size and function remained within the normal range for age and body size. Short-term GH treatment of idiopathic short stature was thus not associated with an increase in risk factors known to be associated with later cardiovascular morbidity. Longer follow up studies will be required to confirm the safety of high-dose GH in this respect. PMID- 1305810 TI - Pz-peptidase is not a matrix metalloproteinase. PMID- 1305811 TI - Biological standardization of pollen allergens from India. AB - Standardization of allergens are achieved by in vitro and in vivo methods. Some of the allergens from Western countries are standardized using biological potency of the extracts but no attempt has been made till now to standardize any of the pollen extracts from India based on biological units. Therefore, we have attempted to standardize two important pollen allergens Ricinus communis and Holoptelea integrifolia by biological methods. Broadly the methods adopted by Dreborg and Grimmer (1983) was followed. Skin prick tests were carried out with the extracts of R. communis and H. integrifolia on 15 allergic patients in five three fold log dilutions starting with 1:10, in 50% glycerinated buffer. Glycerinated buffer (50%) and histamine dihydrochloride (1 mg/ml) were used as negative and positive controls, respectively. The mean wheal diameter obtained with different concentrations showed a gradual systematic fall with increase in dilution. The mean relative diameter (% of histamine reaction) varied from 124.1 +/- 8.9 to 33.7 +/- 6.1 and 78.9 +/- 5.5 to 21.4 +/- 3.8 with the highest and lowest concentrations of R. communis and H. integrifolia pollen antigens, respectively. The histamine equivalent concentration of antigen 1,000 Biological Units (BU) obtained for crude pollen extracts of R. communis and H. integrifolia was 1:17 and 1:22 respectively. PMID- 1305812 TI - Ice cube test in children with cold urticaria. AB - The ice cube test performed in 24 children (6 cold urticaria, 6 healthy, 6 allergic and 6 chronic urticaria) showed that a 3 and 5-minute ice cube test was the appropriate time for the diagnosis of cold urticaria without false positive results. If the test was prolonged to 10 and 20 minutes, 17% and 33% respectively showed false positive results in chronic urticaria other than cold urticaria patients. After four weeks of cyproheptadine therapy, the ice cube test showed only 17% positive at 3 minutes and 33% at 5 minutes. When the ice cube test was performed for 10 and 20 minutes, 67% showed positive results. In conclusion, the ice cube test should be performed for 3 to 5 minutes to diagnose cold urticaria in children. The time should be increased to 10 or 20 minutes if the test shows negative results at 3 to 5 minutes after antihistamine therapy. PMID- 1305813 TI - Bone marrow transplantation in Ramathibodi Hospital: progress report. AB - Bone marrow transplantation has become the accepted treatment for several hematologic disorders. We have done 3 autologous and 6 allogeneic bone marrow transplantations at Ramathibodi Hospital since July 1989 in patients with acute lymphoblastic leukemia, acute non-lymphocytic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma and severe aplastic anemia. Only one patient with aplastic anemia had late graft rejection, but the rest of them engrafted and did well during the median follow up period of 317 days (range: 39 to 962 days) post transplantation. None of the allogeneic BMT had graft-versus-host disease. We use cyclosporin and short course methotrexate for post transplantation immunosuppression. PMID- 1305814 TI - Monoclonal gammopathies and the related autoimmune manifestations in Taiwan. AB - A total of 50,000 patients were surveyed for the presence of monoclonal immunoglobulins during the past two decades. There were 411 cases of monoclonal gammopathies including 243 cases of plasma cell neoplasms and 168 cases of secondary plasma-cell dyscrasia. Among the 227 cases of multiple myeloma and Waldenstrom's macroglobulinemia, there were 49.3% IgG class, 22.9% IgA class, 9.7% IgM class and 13.2% light chain type. In addition, there were 1.3% of nonexcretory myeloma including an IgM type. A relatively high frequency (4.8%) of IgD M-proteins was detected but heavy chain disease was not encountered in the present series. Purified M-components from patients with possible autoimmune manifestations were subjected to immunofluorescence studies. Autoimmune activity of M-proteins was found in a patient of Waldenstrom's macroglobulinemia with peripheral neuropathy, and another patient of cryofibrinogenemia with recurrent purpura and gangrene. In conclusion, a high frequency of IgD myeloma is found in Chinese patients of this area. M-components may have autoimmune activity resulting in unusual clinical manifestations. PMID- 1305815 TI - Interaction of respiratory syncytial virus with human cord blood mononuclear cells. AB - This study on the interaction between respiratory syncytial virus (RSV) and human cord blood mononuclear cells shows that RSV replication can occur in neonatal macrophages. Although neonatal lymphocytes were not supportive of RSV replication, exposure to RSV resulted in significant inhibition of mitogen induced transformation. Both adult and neonatal NK cell cytotoxicity were unaffected by exposure to RSV. These results suggest that RSV has preferential effects on human cord blood mononuclear cell subpopulations. PMID- 1305816 TI - Comparative evaluation of HIV infected foreign students and Indian with AIDS in Chandigarh, India. AB - Out of a total of 1,600 foreign students who came to India between June 1989 and October 1990, 22 were seropositive for HIV-1. Ten showed antibodies to all the gene products. Antibodies to gp160 and p24 were present in all the seropositives while antibodies to p53, p15/17 were significantly higher in healthy seropositives than in patients with full blown AIDS. Absence of antibodies to p15/17 and p53 thus appeared to be a more sensitive criterion of end stage disease than absence of anti- p24 antibodies. When seropositive samples from African students were checked for HIV-2 antibodies by ELISA, 13/22 were found to be positive. Further, 2/10 Indians with full blown AIDS were also strongly positive for HIV-2. These data could be of relevance for formulating future strategies for population-based screening for HIV-2. PMID- 1305817 TI - Human leukocyte antigen (HLA) in respiratory allergy. PMID- 1305818 TI - Immunoassays of amphetamines: immunogen structure vs antibody specificity. AB - Various immunoassays have been developed for the detection of amphetamines. These have varying degrees of cross-reactivity to other drug and food components. Information on the immunogen structures used, and the specificities of the antibodies obtained, have allowed formulation of a "structure-specificity" pattern delineated on the basis of immunochemistry and stereochemistry. The 'structure-specificity' relationship should be useful to future developments of these immunoassays. Specifically, immunoassays intended to detect either amphetamine or methamphetamine with minimal cross-reaction, should employ immunogens with amphetamine (or methamphetamine) derivatized via the para position of the phenyl ring. Such assays should show minimal cross-reaction with other secondary (or tertiary) amines but should strongly cross-react with phenyl ring substituted analogs. On the other hand, assays intended for detection of both amphetamine and methamphetamine should employ amphetamine (rather than methamphetamine) derivatized via its amino group as an immunogen. Such assays should show minimal cross-reaction with other tertiary amines and phenyl substituted amphetamine/methamphetamine. PMID- 1305819 TI - A comparison of different intervals of administration of inhaled terbutaline in children with acute asthma. AB - Thirty asthmatic children, 5 to 14 years of age, 20 boys and 10 girls, were studied while having acute asthmatic attacks. Each group of 10 children received either a single dose of 6 puffs (1500 micrograms) or 3 doses of 2 puffs (500 micrograms) at 5-minute or 15-minute intervals of terbutaline pressurized aerosol inhaler through a 750-ml volumetric spacer. The onset of bronchodilatation was observed within 2 minutes in all. The 3 doses at 15-minute intervals gave the greatest bronchodilatation throughout the 6-hour study period in comparing with the other two regimens. Slightly insignificant increases in systolic blood pressure and heart rate were observed in all groups and there were no statistically significant differences among them. No serious side effects were observed. PMID- 1305820 TI - Detection of IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one by RAST: a serological diagnostic method for sensitivity to pyrazoline drugs. AB - Certain adverse reactions to pyrazoline drugs resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions is not fully demonstrated. In this study, IgE antibodies specific for 1-phenyl 2,3-dimethyl-3-pyrazoline-5-one have been found in 17 out of 19 serum samples from individuals sensitive to pyrazoline drugs with 4-aminoantipyrine discs by Radio Allergo Sorbent Test (RAST). In contrast, we have not found any positive results from 10 normal donors without sensitivity to pyrazoline drugs after ingestion of metamizol 500 mg/day for 14 days. Therefore, our results provide further evidence in favor of an IgE-dependent mechanism in patients suffering from sensitivity to pyrazoline drugs. The determination of specific IgE antibodies could be used as a serodiagnostics method. PMID- 1305821 TI - [Genetic polymorphism of complement component six (C6) in five Han subpopulations]. AB - By using polyacrylamide gel isoelectric focusing followed by immunoassay, the polymorphism of Complement Component Six (C6) was investigated in five Han subpopulations in China. The following gene frequencies were obtained Zhengzhou Han: C6*A 0.4521, C6*B 0.5228, C 6*B2 0.0183, C6*R 0.0068; Lanzhou Han: C6*A 0.4612, C6*B 0.5218, C6*B2 0.0170; Huhhot Han: C6*A 0.4452, C6*B 0.5286, C6*B2 0.0214, C6*R 0.0048; Xi'an Han: C6*A 0.4899, C6*B 0.4874, C6*B2 0.0126, C6*R 0.0101; Hakka of Meizhou, Guangdong Province: C6*A 0.4569, C6*B 0.5152, C6*B 0.0279 (C6*R is the frequency of rare alleles). PMID- 1305822 TI - [A computer simulated test for the long-time change of heterozygote. Analysis of possibility on preserving the heterozygote for long-time in population]. AB - Under the conditions of random mating and selecting. The research by computer simulation analysed the possibility of long-time conserving heterozygote in colong. An important conclusion was obtained. It was impossible to conserve heterozygote for a long time in colong. Therefore it is not necessary to control inbreeding for conserving all genes of colong by reducing gene purity in the work of conserving breeds for farm animal and poultry. PMID- 1305823 TI - [Effects of several primary factors related to establishment of mouse embryo pluripotent stem cell lines (ES cell line)]. AB - Several primary factors related to establishment of mouse embryo pluripotent stem cell lines (ES cell lines) have been tested comparatively. The results of 825 embryos indicated: (1) Delayed blastocysts were more conducive than normal ones to proliferation of inner cell mass (ICM). (2) Culture medium DMEM with 4 500 mg/l glucose was more advantageous than DMEM with 1000 mg/l glucose to the attachment of explanted blastocysts and to the proliferation of ICM. (3) DMEM without sodium pyruvate was beneficial to appearance of ES cell colonies and to their growth. (4) Feeder layer prepared from the primary culture of mouse embryos had very good effects to the growth and culture of ES cells. PMID- 1305824 TI - [Cloning and expression of alpha-hydroxy-gamma-aminobutyl acylase gene of Bacillus circulans NRRL-B3312]. AB - With shot-gun cloning strategy, we used pUB110 plasmid as a vactor to clone DNA fragment of Bacillus circulans NRRL-B3312, which is butirosin producer, into Bacllus subtilis 168. Among the transformants, the results of TLC, bioautography and FAB mass, spectrum analysis for the bioconversion product of No. 733 transformant showed that this transformant could transform kanamycin into amikacin. According to these results, the HABA acylase gene locates on the insert fragment of pUBC733 plasmid harbouring No. 733 transformant. We can confirm that the HABA acylase gene was cloned and expressed in B. subtilis 168. Molecular weight of pUBC733 is 7.3kb. Southern hybridization demonstrated that the 2.8 kb inserted fragment of this plasmid originated from B. circulans NRRL-B3312. The restriction map of pUBC733 plasmid was constructed. PMID- 1305825 TI - [Study on the meiotic mapping and functions of another new osmotic-sensitive gene osm3 in Saccharomyces cerevisiae]. AB - Another recessive nuclear gene mutation of Sacchromyces cerevisiae, osm3, which causes growth inhibition on hypertonic media, has been mapped on the chromosome II by tetrad analysis. Its second-division segregation frequency is about 51.01%, and the map distances between osm3 and the centromere of chromosome II is about 25.51 centimorgans and it is approximately 45 centimorgans far gene gall. The studies on the reverse mutation of osm3 indicated that this osmotic-sensitivity arises from a missense or nonsense mutation in OSM3 locus. The response of yeast to osmotic stress and the mechanism of osm3 gene function were investigated. The results indicated that high intracellular glycerol content is necessary for yeast to grow in hypertonic media; The gene product of osm3 is probably relative to the process of glycerol transportation. Finally, the effect of osmotic stress on fermentability was also discussed. PMID- 1305826 TI - [Construction and characterization of shuttle plasmid pBHG1 in Bacillus thuringiensis and Escherichia coli]. AB - The recombinant plasmid pBHGA was constructed by ligating plasmid pHTA1030 from B. thuringiensis to plasmid pJH101 from E. coli. The recombinant plasmid pBHGA was digested and deleted by various restriction enzymes, generating 14 derived recombinant plasmids differing in molecular weight. The expressible analysis for the plasmid pBHG1 from among the derived plasmids in E. coli HB101 and B. subtilis 168, the results proved the recombinant plasmid pBHG1 is carring promotive region, original region and segregational stability region of B. thuringiensis plasmid pHTA1030. The recombinant plasmid pBHG1 can be high frequency transformation in to B. thuringiensis HD-1 Cry- B and high-expression in B. thuringiensis. HD-1 Cry- B. The plasmid pBHG1 is segregational stability in B. subtilis 168 at 45 degrees C. These plasmids may be useful tools for study of plasmid replication and expression in B. thuringiensis once a reproducible transformation system is available for this organism. PMID- 1305827 TI - [The correlation between the maturation of rbcL transcripts and its flanking sequence in a prokaryotic system]. AB - There is a 15bp large reverse repeated sequence proceeded by a 7bp small one in the 3'flanking region of rbcL of Nicotiana tabacum. A 383 bp of XbaI fragment containing these tandemly repeats was inserted into the plasmid p lambda S delta, at the position between the lambda p and the cat gene. Then these two repeats were separated and deleted systematically to obtain various deletions. The deletion pRT65, pRT74 and pRT83 was sequenced to determine the deleted base pairs exactly. S1 mapping analysis was adopted to investigate the transcripts of these deletions in E. coli JM83. The results showed us that the stability of mature 306bp mRNA relied on the large repeat and a short sequence downstream. The small one was not efficient. The regulation level of the rbcL termination was also investigated. The XbaI-EcoRI fragments from pRT65, pRT74 and pRT83 were transferred into pSP-TT* at the position between the spinach promoter and threonine terminator to construct pRT65, pRT74 and pRT83 respectively. The results from S1 mapping analysis showed that the E. coli RNA polymerase read through the 3' flanking region of rboL gene and terminated at the stop site of threonine terminator. These results suggested that mature rbcL mRNA might be the product precisely processed from a precursor mRNA and the 3' flanking sequence might be the signal for precursor mRNA to be processed to the correct position. PMID- 1305828 TI - Effects of short length immobilization of medial gastrocnemius muscle of growing young adult rats. AB - Effects of four and six weeks of immobilization at short length of gastrocnemius muscle on its architecture at optimum muscle length and length-force characteristics were studied. In general, immobilization effects were similar after 4 and 6 weeks. Smaller physiological cross-sectional area and lower muscle force were found as a consequence of immobilization. Muscle and aponeurosis were shorter. This was shown to be quantitatively related to atrophy i.e. smaller fibre diameter. Despite this atrophy no effects of immobilization on fibre and aponeurosis angles could be shown. Adaptation of the number of sarcomeres in series was found exclusively in distal fibres after 4 weeks of immobilization. No significant effects were found for proximal fibres of muscles at this time nor for any fibres after 6 weeks of immobilization. The effects of immobilization on muscle architecture did not affect the length range of active force exertion. It is concluded that muscle length adaptation as a consequence of short length immobilization is not related to adaptation of number of sarcomeres in series but to the occurrence of atrophy. It is also concluded that atrophy of pennate muscles does not have to be accompanied by a lower fibre and aponeurosis angle. Comparison of immobilized and control group rats indicates that the effects of immobilization can be characterized as a combination of retarded development of several variables and the influence of atrophy and its consequences. PMID- 1305829 TI - Pericytes in human breast stroma and the cells to which they relate. AB - The function of pericytes, the cells nearest the microvascular endothelium, has long been debated. On the basis of ultrastructural studies it is pointed out that they have specialised features in common with endothelial cells of the lymphatic labyrinth of the human breast. The latter are in continuity with the initial lymphatics. These features, which include points of stromal attachment, allow contraction or relaxation of the cell-processes. The cytoplasmic processes of the pericyte, when relaxed, form areas of contact with the blood vascular endothelium. Subsequent contraction may lead to loss of contact and increase in the area of vascular endothelium available for diffusion. The pericyte is thus equipped to act as a regulatory link between the blood vascular endothelium and that of the fine lymphatic system. PMID- 1305830 TI - Tissue and sex differences in the expression of nucleoli in mouse somatic cells. AB - In Mus musculus, the nucleolus organizer regions (NORs), or sites of ribosomal RNA-encoding genes, map at three chromosomal pairs. A silver procedure was modified to stain nucleoli in interphasic somatic cells of mice. The number of nucleoli per cell nucleus was determined in squashed cells of kidney, liver and pancreas obtained from male and female mice. In liver and pancreas cells the average number of nucleoli per cell was 4.84 and 4.66, respectively, and only 2.83 in kidney cells (p < 0.001). Less than 8% of pancreas cells and about 15% of liver cells contained more than 6 nucleoli per cell, which was the maximum expected number. In addition, the number of nucleoli per cell was significatively different (p < 0.01) when male and female liver or pancreas cells (not kidney cells) were compared. In both cases, female cells presented more nucleoli than the respective male cells. Assuming that the available NORs are the same, the variable number of nucleoli in the examined cell types would be the consequence of a tissue specific NOR regulation. The apparent influence of sex on this regulation is noted. PMID- 1305831 TI - The magnetic field. PMID- 1305832 TI - Literature on magnetic fields in life sciences. PMID- 1305833 TI - Calibrating microwave-incubation times for droplet immunostaining: reversible Thermo-Paint as a low cost alternative. AB - Reversible Thermo-Paint R50 (Manufactured by Thermographic Measurements, Ltd., Burton, UK and imported in The Netherlands by Blanken Controls, Loenen (Vel.)) has a yellow colour that changes to orange when a temperature of 50 degrees C is reached. Microscopical glass slides can be painted with R50. Under the droplet on the painted slide an orange disk will appear at the moment the droplet has reached the temperature of 50 degrees C. This test provides us with information about how much energy per minute is available to be absorbed by that precisely defined "test droplet" using a certain setup of the microwave oven. The obtained data can be used to calibrate incubation times for various microwave ovens. The results explain why, when short cycle times are used, immunostaining is highly reproducible. PMID- 1305835 TI - [Menopause and osteoporosis]. PMID- 1305834 TI - [Should we use the WONCA classifications? World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians]. PMID- 1305836 TI - [The content of the nursing consultation at a health center]. AB - AIMS: To describe the care process in the Nursing Station. To analyse the length of a consultation and factors which affect the length. DESIGN: Crossover study. Analysis of the length of the Consultation, using a multiple lineal regression model. SITE. Urban Health Centre. PATIENTS AND OTHERS TAKING PART: All the calls and consultations, both in the patient's home and in the Health Centre, undertaken by six nurses over a period of two weeks. MAIN MEASUREMENTS AND RESULTS: There were 879 consultations. 65.41% of them took place in the treatment room. Ten health problems represented 72% of the work-load. Health education took un the greatest proportion of time. The average time of a consultation was of 10.40 +/- 0.3 minutes. The length of the consultation depended on the professional involved, on the place where it took place, on the number of problems which the patient had and on the nature of the main problem: multiple correlation coefficient = 0.74; F = 67.52 (p < 0.00000001). CONCLUSIONS: The nurse faces a very limited number of health problems. Most of her activities are preventive or to do with prevention. The length of the Consultation in greatly conditioned by the amount of morbidity. PMID- 1305837 TI - [An analysis of the obligatory reporting of meningitis in a pediatric area]. AB - AIMS: To find out the validity, reliability and quality of the epidemiological information which comes from the System of Statutory Declarations. The example used is the incidence of Meningitis. DESIGN: Descriptive study of the coverage of the Declaration, with the help of the EDO (Illnesses requiring a Statutory Declaration) index, of the pediatric (up to 14 years old) cases of meningitis attended in our Area between 1984 and 1989. We analysed how the Declaration had been filled in and the agreement between the information gathered through the notification system and clinical records. SITE. The whole network of epidemiological vigilance: hospitals, provincial epidemiological services and primary care services. PATIENTS: All the cases of child meningitis (120 cases) seen in the Mother and Child Hospital in our area between 1984 and 1989. MAIN MEASUREMENTS AND RESULTS: The meningitis declaration covered 47.5% of the total number of cases seen. In the cases declared, the diagnosis of meningococcal meningitis on the EDO index was 89.5%, whereas the rate in the clinical reports was only 20%. Thus agreement in the diagnosis does not exceed what could be produced by chance (Kappa = 2.5%; p = NS), as agreement for all diagnoses is 7.1%. CONCLUSIONS: Our results demonstrate a low level of declaration, poor standard of compliance and scant agreement between the Statement of Declaration and the clinical report. The validity and reliability of this information is extremely low and suggests a need to re-consider the usefulness of this vigilance system for health-service practice, especially in Primary Health Care. PMID- 1305838 TI - [The attitudes of primary care professionals on mental patients and psychiatric care]. AB - AIM: To describe the views of different primary care professionals regarding mental illness, psychiatric patients and mental health care. DESIGN: Crossover survey. SITE. Primary care centres in a health zone. PARTICIPANTS: All the primary care centre professionals and social service base teams. Out of 66 possible subjects, 61 answered the questionnaire. MEASUREMENTS AND RESULTS: A questionnaire composed by ourselves about peoples' opinions was given. The chi 2 test was then used to analyse the questionnaire, both item by item and by means of the distribution of frequencies and comparisons. On some items differences between Health Professionals and social service staff occurred. But there were no differences between doctors and nursing staff, nor between men and women (level of importance: 0.50). For 91% of those surveyed, mental health is an illness like any other. 87% believe psychiatry is a science; and 77% that psychiatry is related to the rest of medicine. 48% believe that the majority of mental disturbances are untreatable. 80% affirm that psychiatric admissions should be into special hospitals. CONCLUSION: The authors highlight the need to overcome the discrepancy between positive attitudes on the theoretical side and a reluctance to integrate those attitudes into practice. PMID- 1305839 TI - [Tobaccoism in medical students]. AB - AIM: To evaluate medical students' understanding of the harmfulness of tobacco; their attitude to it; and the spread of tobacco addiction among them. DESIGN: This was a crossover study, using information collected through a self-answer questionnaire. SITE. It was carried out in the Faculty of Medicine in the Autonomous University of Barcelona. PARTICIPANTS: The people under study were the 490 students registered in the first year of Medicine and doing the Biostatistics course. MAIN MEASUREMENTS AND RESULTS: The information was collected by means of a voluntary self-answer questionnaire, which was distributed during class-hours of the Biostatistics course. 68% of those registered answered. This broke down into: 25.7% smokers; 25.1% ex-smokers; and 49.2% non-smokers. 88% of students expressed total agreement as to the harmfulness of tobacco, though there were important differences between smokers and non-smokers (p < 0.01). The illness which they related most closely to tobacco addiction was Lung Cancer; and the least closely related was Bladder Cancer. Only 30% would warn healthy smokers about the risks attached to their addiction. 50% believe it is the doctor's responsibility to convince the general population to give up smoking. CONCLUSIONS: The spread of tobacco addiction is lower among medical students than among the general population of the same age and than among health professionals. We think it is essential to integrate an action programme against tobacco addiction into the overall study plan. PMID- 1305840 TI - [Lumbago cases seen at a health center]. AB - AIM: The main aim is to describe the cases of mechanical lumbalgia in relation to clinical and demographic variables, in the period between February and June 1989. The collateral purpose is to analyse the relationship between analgesic/NAI treatment as regards the time needed to resolve the problem. DESIGN: This is an observational prospective study. The cases included under the second aim are distributed at random. SITE. The study was carried out in the Primary Care Centre of Deltebre, a rural town of 10,000 inhabitants. PATIENTS AND OTHERS PARTICIPANTS: The consultations for rheumatoid lumbar pain were 355. Of these, 183 were first visits, which were the object of the descriptive study. Out of these, 125 were lumbalgias of the posterior branch and are the target population of the analytical study. INTERVENTIONS: Paracetamol (on its own or with codeine) taken orally was used as an analgesic. Piroxicam, Indometazine, Ketoprofen or Diclofenac taken orally, rectally or intramuscularly was used as an anti inflammatory. MAIN RESULTS AND MEASUREMENTS: In cases between the ages of 40 and 49 in the case of men, and of 40 and 59 in the case of women, an increase in relation to the municipal census was observed, with p < 0.01 and 0.001. There was no difference in the time of resolution between the cases treated with analgesics and those treated with NSAI. CONCLUSIONS: Future studies will have to analyse the increase in lumbalgias in the 40 to 59 age-group. The number of cases off-work signifies a health cost. Drug treatment plays no part in the resolution, which agrees with a previous reference. PMID- 1305841 TI - [An epidemiological study of arterial pressure in a schoolchild population]. AB - AIM: To know the prevalence of high blood pressure in childhood. DESIGN: Epidemiological transversal study. SITE. School population, level community. POPULATION: A population of 566 children of 6, 10 and 13 years old of Madrid public schools. MEASUREMENTS AND RESULTS: The blood pressure measure was registered two times according to the WHO's guidelines. We considered the first sound as systolic blood pressure and the fifth auscultatory phase as diastolic blood pressure. Considering as hypertensive those subjects whose blood pressure are higher than percentile 95 for their age and sex, the total prevalence of systolic hypertension was 5.8% and the total prevalence of diastolic hypertension was 1.4% in both genders. We realized that systolic hypertension prevalence is higher in males for all ages and its is also higher than the results offered by similar studies. It doesn't happen the same thing in the diastolic hypertension prevalence which we found that the measurements registered in males are higher than females but in contrast with other studies we found similar prevalence. CONCLUSIONS: We need to identify early the presence of higher blood pressure with the purpose of to prevent in time. PMID- 1305842 TI - [The influence of the social factor on the response to a vaccination program]. AB - AIM: To make an analysis of the different reasons for the response to three subprograms of anti-tetanus vaccination. DESIGN: Retrospective descriptive analysis. SITE. Within the primary care field: in the rural clinic of Izarra Urkabustaiz in the province of Alava. PATIENTS: Inhabitants who live and/or work in Izarra-Urkabustaiz were allocated for the purposes of vaccination to three groups: 130 workers in a rubber factory, 116 citizens over 65 and 65 people aged 24, 34, 44, 54 and 64. MEASUREMENTS AND RESULTS: We have used the chi 2 test to analyse the qualitative variables and the confidence interval, in order to find the accurate level of response. We have established at 0.05 the threshold of permitted error and significance. The confidence intervals of the vaccination response have been 74-88 for those over 65, 54-74 in the factory and 4-21 in the "decade" subprogram. The difference has been very significant (p < 0.0001). CONCLUSIONS: The factors which best explain such differences are those of a sociological nature, inasmuch as the level of acceptance and response is directly related to the amount of cohesion in the group. PMID- 1305843 TI - [The management of the elderly patient in primary care. Guidelines]. PMID- 1305844 TI - [Myalgias and muscular rigidity in a 68-year-old man]. PMID- 1305845 TI - [The investigation of chronic neutropenia]. PMID- 1305847 TI - [The education of pediatrics residents in primary care]. PMID- 1305848 TI - [Pre-degree education in primary care. The English example: Newcastle]. PMID- 1305846 TI - [Cardiac tamponade as the clinical manifestation of a pulmonary adenocarcinoma]. PMID- 1305849 TI - Role of the Office International des Epizooties in protecting the health of free ranging mammals. AB - The various activities undertaken by the Office International des Epizooties (OIE) since 1924 to protect the helth of free-ranging mammals are outlined and discussed. Two types of activity have been conducted over the years: --The first type promotes measures to protect the health of free-ranging mammals in order to safeguard the health of domestic animals and human beings. These measures have prevented the propagation of the highly contagious diseases of animals and the more serious zoonoses. --The second type aims at protecting the health of free ranging mammals in order to maintain the fauna and the natural equilibrium. Ecological and epidemiological studies are promoted with a view to effective management of wildlife populations and overcoming the associated health risks. By virtue of its close contacts with officials in charge of animal health in 126 Member Countries, the OIE has made a noteworthy contribution to the protection of populations of free-ranging mammals. PMID- 1305850 TI - Epidemiology of sylvatic trichinellosis in north-western Italy. AB - Muscle samples from 7,142 wild boars (Sus scrofa), 80 free-ranging hogs, 1,462 red foxes (Vulpes vulpes) 90 mustelids, 15 Alpine marmots (Marmota marmota), 873 rodents and 92 insectivores were examined for Trichinella Railliet, 1895. A wild boar, a badger (Meles meles) and 30 foxes (2.1%) were found to be infected. Eleven vulpine isolates and the wild boar isolate were identified as Trichinella britovi. These results show that the wild boar has little significance as a reservoir of T. britovi in the area under study. A vulpine isolate resulted in low infectivity in experimentally-infected swine. The prevalence of trichinellosis in the vulpine population is higher in the mountains than in lowland areas and indicates the key role played by this carnivore in the epidemiology of T. britovi. Preliminary results from four field trials seem to demonstrate that differences in attitudes towards cannibalism exist between mountain and lowland foxes. PMID- 1305851 TI - Parasitosis of stray dogs in north-eastern Spain. AB - The authors analysed 42 stray dogs in north-eastern Spain. Of these, 29 dogs were parasitised by one or more helminth species. The parasites found were intestinal nematodes (59.52%) and cestodes (47.61%). Differences between urban stray dogs and feral dogs are discussed. PMID- 1305852 TI - [Detection of the eggs of Echinococcus multilocularis Leuckart, 1863, in the feces of the fox (Vulpes vulpes Linnaeus, 1758) by the polymerase chain reaction]. AB - The polymerase chain reaction (PCR) was applied to the identification of eggs of Echinococcus multilocularis in faeces from foxes. The test was positive in three of six faeces samples from foxes which were harbouring adult worms, and in one of four samples from foxes in which no adult E. multilocularis was found in the intestines. These initial results show that it is possible to use PCR to identify E. multilocularis eggs in faeces. PCR can be used to complement examination of intestinal contents, showing that the distribution of eggs in faeces is uneven. The sensitivity of the test was estimated to be 50 eggs in 5 g of faeces. Further work is needed to confirm these initial results before the test can be used more widely. PMID- 1305853 TI - Parasitological and serological studies on the prevalence of Echinococcus multilocularis Leuckart, 1863 in red foxes (Vulpes vulpes Linnaeus, 1758) in Switzerland. AB - In the Canton of Zurich in Switzerland, 1,252 red foxes (Vulpes vulpes) were examined during 1990-1991 for intestinal stages of Echinococcus multilocularis using the mucosal smear technique. Special safety precautions were employed during examination. An average of 35% (432 foxes) were infected, mostly with low to medium numbers of gravid worms producing thick-shelled eggs. In the eleven districts of the Canton, prevalence rates varied between 13% and 57%. An average of 29% of the foxes had antibodies in serum or body fluid against a highly species-specific antigen of E. multilocularis (Em2-antigen). The fact that foxes with intestinal E. multilocularis infection have been found in all parts of the Canton of Zurich indicates a relatively high potential infection risk for humans, but apparently the risk is reduced by certain extrinsic or intrinsic factors which have yet to be determined. PMID- 1305854 TI - [Histopathologic study of the host-parasite relationship: the earthworm-, wild boar-metastrongyle model]. AB - A histopathological study was conducted on two hosts of metastrongyles (Metastrongylus sp.): earthworms and wild boars (Sus scrofa Linnaeus, 1758). In the earthworm intermediate host there were rare granulomas outside the normal site occupied by larvae (blood sinuses of calciferous glands). Given the small number of these reactions, they could not constitute a limiting factor for parasitism in this host. However, the lungs of wild boars contained numerous lesions associated with the presence of these nematodes. Such lesions, often inflammatory, were part of an immunological defence mechanism which controls the extent of parasitism in wild boar. PMID- 1305855 TI - Dermatophilosis in camels (Camelus dromedarius Linnaeus, 1758) in Kenya. AB - Natural dermatophilosis (caused by Dermatophilus congolensis Van Saceghem, 1915) has only recently been described in camels (Camelus dromedarius). Further work has shown that the disease is actually widespread. At the Ol Maisor farm where it was first diagnosed (in the Laikipia district of northern Kenya), detailed investigations have revealed that thirty camels (ten calves and twenty adult animals) were infected. The signs varied from mild to more than 50% skin involvement. Patches of wool on the rump were easily detachable with many hard, white crusts. Similarly, another twenty camels from a totally different area of northern Kenya (Samburu district) were found to be infected with D. congolensis. Bacterial isolation was used to confirm the diagnosis. At Ol Maisor farm, twenty sheep were also found to have severe dermatophilosis. There were scabs and many areas of wool shedding. The shed wool had crusts similar to those observed on camels. Experimental infection with D. congolensis isolated from camels was conducted, by means of scarification, on the skin of two goats. The same experimental infection was possible in two calves, taking two weeks to become established. After thirty days there were disseminated foci of infection on the heads of the calves, especially around the eyes. Although these findings cannot show the actual source of D. congolensis, it is possible that the same organism causes dermatophilosis in the different animals. PMID- 1305856 TI - Myxomatosis: population dynamics of rabbits (Oryctolagus cuniculus Linnaeus, 1758) and ecological effects in the United Kingdom. AB - In 1953-1955, myxomatosis spread among rabbits (Oryctolagus cuniculus) in the United Kingdom, causing 99% mortality. Subsequently, there was a gradual increase in rabbit numbers. By 1955, the Ministry of Agriculture, Fisheries and Food (MAFF) had already found attenuated strains of myxoma virus. By 1970, genetic resistance had appeared. In the 1970s, mortality declined to 47-69% with only approximately 25% of rabbits infected, giving a field mortality of 12-19%. However, myxomatosis is persistent, generally showing a major prevalence peak in autumn and often a minor peak in spring. An eight-year MAFF experiment in which prevalence of the disease was artificially reduced indicates that myxomatosis remains a significant factor in population regulation. After rabbit numbers fell in the 1950s, important ecological changes took place: vegetation altered due to reduced grazing pressure, predators were affected by the reduction of a major prey species and these changes also affected many other animals. Currently, rabbit numbers have returned to approximately one-third of pre-myxomatosis levels and this is causing damage to farm and conservation habitats. PMID- 1305857 TI - Sarcoptic mange in Swedish wildlife. AB - Mange caused by Sarcoptes scabiei var. vulpes appeared among red foxes (Vulpes vulpes) in Scandinavia (south-west Finland) for the first time in this century in 1967. The disease was most probably introduced by foxes crossing the Gulf of Finland from Estonia. The mange epizootic spread northwards through Finland and reached Sweden in late 1975, when mangy foxes appeared in the northern part of the country. In 1984, mange was observed in most parts of Sweden. The disease was observed to spread rapidly in boreal areas, whereas it spread more slowly in agricultural areas. Mortality due to mange was very high. The duration of the disease before death due to emaciation has been shown experimentally to be over 90 days. An outbreak of fox mange among Arctic foxes (Alopex lagopus) occurred in 1986. The local population of Arctic foxes was caught and successfully treated. The following year, treated foxes were caught again and no signs of disease were found. Sporadic cases of fox mange have also been diagnosed in lynx (Lynx lynx), pine marten (Martes martes) and domestic dogs. Single cases have been observed in other species: wolf (Canis lupus), mountain hare (Lepus timidus), domestic cat and horse. No cases of sarcoptic mange have been recorded in the badger (Meles meles). At present, although fox mange occurs as an epizootic in local populations, the number of foxes has increased again in many parts of Sweden. PMID- 1305858 TI - The ecology of tularaemia. AB - Tularaemia, a zoonotic disease caused by the bacterium Francisella tularensis McCoy, 1912, is reported from North America, Europe and northern parts of Asia, but not from the Southern Hemisphere. Two subspecies of F. tularensis are recognised: the highly virulent type A and the milder type B, with additional subdivisions reported. Tularaemia has been reported in more than 250 animal species including man, other mammals, birds, fish, amphibians, arthropods and protozoa. Type A is reported to have a terrestrial cycle with the main reservoirs being cottontail rabbits (Sylvilagus spp.) and ticks. Type B is reported to have a mainly water-borne cycle with aquatic rodents as reservoirs, e.g. muskrats (Ondatra zibethicus) and beaver (Castor canadensis) in North America, and ground voles (Arvicola terrestris) in the former Soviet Union. In Europe, tularaemia is most frequently seen in hares (Lepus spp.) although hares probably do not constitute a reservoir for the disease. Tularaemia is transmitted by direct contact with infected animals, through contaminated water or food, or by vectors such as mosquitoes or ticks. The disease normally occurs as an epidemic, both in man and in animals, depending on the types of reservoir involved and the means of transmission at different times of the year. PMID- 1305860 TI - Epidemiology and control of rabies in bats in The Netherlands. AB - The first case of bat rabies in the Netherlands was recorded in 1987. Since then, 2,540 bats have been examined. In total, 186 bats belonging to two species were found positive for rabies: 182 Eptesicus serotinus and 4 Myotis dasycneme. The virus isolates from the two species were found to be different. Approximately 20% of the E. serotinus bats sent for examination were found positive. The epidemiological findings suggest a stable situation of infection north of the Rhine and the Meuse. A total of 174 humans received post-exposure treatment after direct contact with a positive or suspected bat. The public has been warned not to touch bats and, if contact does occur, to send the bat for rabies examination. The authorities also advise post-exposure treatment for dogs and cats which have had contact with a rabies-positive bat. PMID- 1305859 TI - Crassicaudosis: a parasitic disease threatening the health and population recovery of large baleen whales. AB - This communication briefly reviews knowledge of the systemic disease caused by Crassicauda boopis in blue whales (Balaenoptera musculus), fin whales (B. physalus) and humpback whales (Megaptera novaeangliae). Infections with this giant nematode characteristically incite a chronic inflammatory reaction of the blood vessels which drain the kidneys. In this critical location, the parasite induced lesion can cause complete vascular occlusion and kidney failure. Whale calves and juveniles typically suffer the heaviest parasite burdens following transplacental infection of the developing whale foetus. There is also probable whale-to-whale transmission post-partum, involving urinary contamination of the environment with C. boopis eggs and larvae. The frequency of the infection can exceed 95%. Haematological findings suggest that systemic pathological effects are typical at the population level. Gradual development of occlusive lesions in the renal veins appears to correlate with a major peak in natural mortality at about one year of age. To date, all findings support the conclusion that premature death caused by C. boopis infection is potentially a major impediment to population recovery of affected whale species. This suggests the interesting possibility of actively encouraging the population recovery of three species of large baleen whales. Such a restoration effort would entail remotely-deployed anthelminthic therapy administered, at sea, to infected whale cows and calves. PMID- 1305861 TI - Serological survey for bovine bacterial and viral pathogens in captive Arabian oryx (Oryx leucoryx Pallas, 1776). AB - Tests for antibodies to bovine bacterial and viral pathogens were conducted on 239 sera from 128 Arabian oryx (Oryx leucoryx) from seven locations (Taif, Riyadh and Mahazat as Said, Saudi Arabia; San Diego, United States of America [USA]; Shaumari, Jordan; Qatar; and Bahrain). No antibodies to Pasteurella multocida type E or epizootic haemorrhagic disease 1 virus were found. Antibodies to Brucella abortus, P. multocida type B, P. multocida type D, lumpy skin disease virus and Akabane virus were detected in 2, 1, 5, 2 and 1 animals, respectively. Evidence of P. multocida type A, Coxiella burnetti, Chlamydia psittaci and parainfluenza 3 virus was found in 3 herds (prevalence in the main herd [n = 78]: 8%), 3 herds (8%), 6 herds (7%) and 5 herds (15%), respectively. Evidence of antibodies against bluetongue virus was found in five oryx from the USA and in one oryx from the Taif herd. Antibody vaccinal titres against rinderpest virus (and the virus of peste des petits ruminants, due to cross-reactions) were found in almost all the herds. This is the first report of antibodies against B. abortus, C. burnetti, C. psittaci, parainfluenza 3 virus and Akabane virus in the genus Oryx. PMID- 1305862 TI - Trypanosomiasis in the black rhinoceros (Diceros bicornis Linnaeus, 1758). AB - A black rhinoceros (Diceros bicornis) moved from a tsetse-free to a tsetse infested area in Kenya was monitored for two months following translocation. The animal acquired a Trypanosoma vivax infection from natural tsetse challenge, but survived without requiring treatment with trypanocides. The infection was characterised by moderately high parasitaemia, with symptoms of anaemia, leukopaenia and thrombocytopaenia. Although confirmed to be T. vivax through deoxyribonucleic acid hybridisation and parasite development in tsetse in the proboscis only, the parasite had unusual morphology and motility. It also failed to infect normally susceptible hosts such as cows and goats, and produced unusually low infection rates in Glossina morsitans centralis and G. brevipalpis. PMID- 1305863 TI - [Changes in the properties of the 5-HT1 receptors in the brains of rats, the progeny of parents consuming morphine for a long time]. AB - Studies were performed in two-month rats whose parents had been given morphine for a long period before mating. Considerable changes were found in the properties of rat brain 5-HT1 receptors, which manifested as increased number of ligand binding sites (Bmax) and higher KD, which indicates a lower receptor affinity for ligand. Single morphine administration to the animals caused normalization of the properties of the receptors. PMID- 1305864 TI - [The protective action of nimodipine on the ischemic myocardium]. AB - The experiments with unconscious cats and dogs have demonstrated that the calcium antagonist nimodipine has a profound anti-ischemic property. The drug reduces the average value of ST-segment elevation in multiple epicardial ECG leads, during acute myocardial ischemia. Nimodipine maintains cardiac pump and contractile functions, elevates ATP levels in the arbitrarily intact and ischemic myocardium of the left ventricle during 40-min occlusion and 60-min reperfusion of the coronary artery. The protective action of the drug is unassociated with enhanced collateral coronary circulation. PMID- 1305865 TI - [The activity of mitochondrial enzymes in the myocardium in chronic coronary failure during the administration of antianginal agents]. AB - The experiments with Chinchilla rabbits indicated that the activity of mitochondria-associated enzymes changed hetero-directionally in chronic coronary insufficiency. The activity of creatine kinase changed most greatly. Obsidan and finoptin were found to show a different effect on the activity of the tested enzymes in the cardiac mitochondria during experimental coronary insufficiency. PMID- 1305866 TI - [The effect of proanthocyanidins from Alhagi pseudoalhagi (M. B.) Desv on the course of experimental myocardial infarct]. AB - Intravenous proantocyanidin isolated from Alhagi pseudoalhagi (M. B.) Desv, 5-10 mg/kg, has no effects on the general hemodynamics and cardiac contractility of intact rats and rabbits. The agent given to animals with experimental myocardial infarction reduces serum creatinine phosphate levels and lipid peroxidation both in the myocardium and serum, as estimated by the amount of malonic dialdehyde and dienic conjugates), normalizes free fat acid content and cardiac phospholipid spectrum. At the same time the size of a myocardial necrotic zone became diminished. PMID- 1305867 TI - [The effect of the table salt substitute sanasol on arterial pressure, water-salt metabolism and kidney functions in experimental pathology of circulatory homeostasis]. AB - The potassium-containing salt substitute sanasol was examined for its effects on blood pressure and renal function in normo- and hypertensive rats, as well as on the edematous syndrome in circulatory insufficiency. The antihypertensive and occasional antiedematous effects of sanasol resulted in unfavorable changes in electrolyte balance. Sanasol was found to be ineffective in experimental renal failure. PMID- 1305868 TI - [The effect of isradipine on the central and cerebral hemodynamics of patients with circulatory encephalopathy and hypertension]. AB - The new dihydropyridine calcium antagonist isradipine versus nifedipine was tested in 41 patients with essential hypertension and cerebrovascular insufficiency. The tests have shown that isradipine shows all hemodynamic effects by significantly improving cerebral blood flow and it is better tolerated than nifedipine. It is concluded that isradipine is an effective agent in the long term management of hypertensive patients at a high risk for cerebral hypoperfusion. PMID- 1305869 TI - [The gastroprotective and antiaggregant activities of 13-azaprostanoids]. AB - Some 13-azaprostanoic acid derivatives were shown to have a high cytoprotective activity against the damaging effect of ethanol on the gastric mucosa in non strain rats and affect ATP- and arachidonate-induced platelet aggregation in the whole blood of rabbits and rats in a different way. The gastroprotective activity that is common to natural and synthetic prostanoids is not closely related to the chemical structure of the compounds. On the contrary, the trends of these compounds to affect the induced platelet aggregation depend on the modification of both the cyclic moiety and both chains of a prostanoid molecule. PMID- 1305870 TI - [The effect of bonnecor on blood coagulability and thrombocyte aggregation in transient myocardial ischemia]. AB - The experiments on conscious rabbits have indicated that bonnecor given in doses of 0.05 mg/kg and 0.5 mg/kg accelerates clot formation and platelet aggregation, without changing the density of a thrombus. In experimental transient myocardial ischemia, the agent decreases the hypercoagulative change associated with the damaging effect of occlusion and reperfusion. PMID- 1305871 TI - [The effect of antidepressants on the reorganization of circadian mobility in normal and stressed rats after a shift in the light regimen]. AB - Changes in the light regime caused a continuous reorganization of circadian motor rhythm with a gradual formation of a new pattern of circadian mobility. Both chronic administration of imipramine and maprotiline and pain stress-induced simulation of depression modified this process in different ways. However, when antidepressants were given, impairments in rhythm resynchronization attenuated in the stressed rats to a great extent. PMID- 1305872 TI - [The effect of mildronate on erythrocyte membrane permeability in experimental lung pathology]. AB - With the use of the erythrocyte osmotic and acidic resistance methods, the experiments on intact albino rats by applying a model of chronic non-specific lung diseases and those in vitro have shown that mildronate has a membrane stabilizing action only when given in high doses (500 mg/kg) and concentrations (10(-3)-10(-4) M). When used in low doses (5, 25, 50, and 200 mg/kg) and concentrations (10(-5)-10(-7) M), in produces no positive effect. PMID- 1305873 TI - [The metabolism and biological activity of glucuronidation substrates in experimental diabetes mellitus]. AB - The study was undertaken to examine the impact of experimental diabetes mellitus on the biotransformation of some drugs, their toxicity and hypoglycemic action, as well as on the biotransformation of endogenous testosterone and the androgenic status. The accelerated metabolism of both exogenous and endogenous substrates which occurred in diabetes mellitus caused a decrease in their biological activity. PMID- 1305874 TI - [The effect of desferal on the cellular proliferative activity of the mouse spleen, thymus and bone marrow]. AB - CBA mice were given a single Desferal dose (50 mg/kg). The mice received 3H Thymidine 1 hour before they were killed. They were killed 1, 2, 6, or 9 hours after Desferal. Radiometry, and autoradiography were used to determine the level of DNA synthesis. Desferal was found to stimulate splenic 3H-incorporation 3 hours after drug injection and to increase the DNA-synthesizing cell fraction. In contrast, the agent inhibited 3H-incorporation in the bone marrow and thymus 9 hours after injection. This suppressive affect was accompanied by a decrease in the DNA-synthesizing cell fraction in these organs. In the thymus, there was a significant increase in the DNA-synthesizing cell fraction among lymphoblasts 1 and 3 hours following the administration of Desferal. PMID- 1305875 TI - [The absence of stereoselectivity in propranolol uptake by the lungs]. AB - Propranolol (P) is known to be actively captured by the lungs of experimental animal and man. To elucidate the mechanism of the phenomenon, the authors studied the P enantiomeric ratio in the serum from the left ventricle 0-10, 10-20 and 20 30 s after bolus injection of P (0.5 mg) into the pulmonary artery of 8 patients catheterized for coronary angiography. The total P concentrations and enantiomeric ratio were measured by non-stereoselective and stereoselective high performance liquid chromatography. The solid-phase extraction method was used for extracting P from the serum. It showed a small, but significant increase is S( )/R(+) ratio (to 1.18 +/- 0.12, P < 0.05 vs 1) which was, however, almost the same when measuring this after adding P to serum of the same patients (1.11 +/- 0.05, P > 0.05 vs 1.18). Thus, propranolol uptake by the lung during a single passage is not stereoselective and hardly involves some active process. PMID- 1305876 TI - [The possible mechanisms of the interaction of hepatotropic diagnostic agents with proteins]. AB - The phenomenon of precipitation in protein solutions after addition of hepatotropic diagnostic media is described. The examination of different proteins and media allows the coagulative mechanism to be proposed, through which the electrostatic interactions between di- and polyvalent ligands with positively charged protein groups play the major role. It is suggested that the described phenomenon contributes to the nephrotoxicity of some drug groups. PMID- 1305877 TI - [The nonspecific mechanisms of the pharmacological correction of motoneuron trophic failure in experimental botulin poisoning]. AB - Cobalamines, leukovorine, cymidine phosphocholine, dalargin are pharmacological agents that affect the support of motoneuronal trophic functions, unlike the actoprotector bemityl, prevent the development of fatal botulinic intoxication, but have no effects on the specific mechanisms of botulinic damage when the threshold concentrations of toxin achieve target cells. The depotentiating effect of the drugs is associated with the increased natural degradation of botulinic toxin in its target cells. PMID- 1305878 TI - [Essentiale as an immunomodulator in a toxic liver lesion]. AB - Tetrachlormethanum used in Wistar rats caused an increase in their immune response to sheep red cells, followed by its decrease. Administration of essential in combination with tetrachlormethanum prevented the accumulation of immunomodulating agents and impairment of an immune response to sheep red cells. PMID- 1305880 TI - [The activities of aldehyde dehydrogenase, GABA-aminotransferase and succinic semialdehyde reductase in the brain of rats with different preferences and tolerances for ethanol]. AB - The formation and catabolism of aldehydes were compared in the hemispheres and brain stem of rats preferring ethanol (EP) or water (WP) and of those which were high tolerant (HT) and low tolerant to the hypnotic effect of ethanol. It was shown that aldehyde dehydrogenase was more active in the brain stem of HT-EP rats than that of HT-WR or LT-EP animals, whereas GABA aminotransferase is most active in the hemispheres and brain stem of LT-EP rats. The total activity of succinic semialdehyde reductase was equal in all the groups studied; however kinetic analysis suggest that the enzyme has a higher affinity for the substrate and coenzyme in the brain stem of HT-EP rats. Ethanol administered to HT-EP animals suppressed aldehyde dehydrogenase in the brain stem, unchanged GABA aminotransferase and activates succinic semialdehyde reductase in the two brain structures. PMID- 1305879 TI - [The therapeutic efficacy of alloxime in experimental carbamate pesticide poisoning]. AB - The new cholinesterase reactivator alloxime, 10 mg/kg, shows a marked therapeutical benefits in acute intoxication rats with carbamine pesticides such as carbofuran, pirimor, elocron. The therapy of alloxime in combination with atropine, 10 mg/kg, results to their combined therapeutical effect, the toxicity of carbofuran, elocron, and pirimor (by LD50) decreasing by 8.4, 5.6, and 3.5 times, respectively). The mechanism of alloxime's therapeutical action is due to its capacity to restore cholinesterase activity in the central nervous system, normalizing neuromuscular transmission and hepatic and renal cytochrome P-450 levels. PMID- 1305881 TI - [The antihypoxic action of malonic acid]. AB - Malonic acid showed a protective action on rats in acute hypoxic hypoxia. The antihypoxic effect of this compound is unassociated with its action on succinate dehydrogenase and may be mediated through the changes in hormonal metabolic regulation. PMID- 1305882 TI - [The effect of phytin, benzonal and their combination administered prophylactically on the pharmacodynamics of drugs metabolized in the liver in hypokinesia]. AB - Hexenal, meprobamate, amidopyrine and ethylmorphine produced a significantly marked effect in animals under hypokinesia as compared with normal rats. When phytin, benzonal and their combination were used for preventive purposes, impaired pharmacodynamics of the tested drugs metabolizing in the liver disappeared. The investigations demonstrated that the preventive use of phytin in combination with benzonal is the most optimal in correcting the impairments of drug pharmacodynamics in hypokinesia. PMID- 1305883 TI - [An analytical variant of the rapid "one-point method" for determining mean effective doses]. PMID- 1305884 TI - [The clinical pharmacology of theophylline]. PMID- 1305885 TI - [Poisoning by cardiac glycosides]. PMID- 1305886 TI - [The anti-inflammatory properties of diuretic agents]. PMID- 1305887 TI - [The undesirable effects from the long-term use of heparin and the approaches for their elimination]. PMID- 1305889 TI - Combination of interleukin-2 and interferon-alpha in renal cell carcinoma and malignant melanoma: a phase II clinical trial. AB - A total of 22 patients with metastatic renal cell carcinoma or malignant melanoma were treated in a phase II study to assess the safety and efficacy of combination therapy of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). 3 x 10(6) U/m2/day recombinant human (rh)IL-2 was given in repetitive cycles by continuous 24-h infusion from day 1 to day 4; 6 x 10(6) U/m2/day rhIFN-alpha was given subcutaneously on days 1 and 4. There was one complete remission and two partial remissions in the renal cell carcinoma group and two partial remissions in the malignant melanoma group, giving an overall response rate of 24% in 21 evaluable patients with a median response duration of 5+ months. Toxicity was moderate, with hypotension, fever, chills, nausea, neurotoxicity, and dermatitis as prominent side effects. Measurement of circulating cytokine levels showed increased serum tumor necrosis factor-alpha (TNF), interferon-tau, and soluble interleukin-2 receptor levels during each cycle with a tendency to higher concentrations of TNF in responders as compared to nonresponders. With regard to therapeutic efficacy and tolerance, our approach might represent an alternative to the high-dose protocols and the labor- and cost-intensive strategies of adoptive immunotherapy. PMID- 1305888 TI - [The ultrastructural characteristics of the changes in sections of the rat brain under piracetam exposure]. AB - Rat experiments have shown that intraperitoneal piracetam leads to formation of abundant coated vesicles in the neurons of the sensomotor cortex, hippocampus, and central gray matter. Concurrently, subsuperficial cisterns form under the plasmalemma of nerve cells. The interneuronal contacts are characterized by long term excitation without destructive changes in synapses. It is suggested that piracetam is able to increase the number of synapses in some brain regions at the expense of sprouting. PMID- 1305890 TI - Muramyl peptide adjuvants for Plasmodium falciparum and Plasmodium vivax circumsporozoite vaccines in rodent model systems. AB - Circumsporozoite proteins from the malaria parasites Plasmodium falciparum and Plasmodium vivax were expressed at high levels in the yeast Saccharomyces cerevisiae. Recombinant proteins varied both in length and in number of the natural amino acid repeat motifs. The proteins were purified and used to immunize mice, guinea pigs, and rabbits. Novel muramyl peptide adjuvants were used that increased the immune response as measured by ELISA assays, indirect immunofluorescence of fixed sporozoites, and the invasion of cultured liver cells by live sporozoites. These results suggest that an improved humoral response to recombinant circumsporozoite vaccines might be achieved by varying the design of the recombinant protein and by the use of novel adjuvant systems. PMID- 1305891 TI - Trace amounts of murine immunoglobulin in affinity purified leukocyte interferon alpha are not immunogenic. AB - Human leukocyte-derived interferon alfa-n3 (Alferon N Injection) is purified to very high specific activity over a murine immunoaffinity column specific for human interferon alpha. Trace amounts of murine immunoglobulin copurify with the interferon alfa-n3. Three populations of individuals were studied for the development of human anto-murine antibodies (HAMA), that is, normal donors, Condylomata acuminata patients receiving interferon alfa-n3, and Condylomata acuminata patients receiving placebo. High and variable endogenous levels of HAMA were observed in all three populations. The same relative increase in HAMA was seen in the placebo as in the interferon alfa-n3 treatment groups. The data demonstrate that intralesional injection of the interferon alfa-n3 did not induce the development of HAMA. PMID- 1305892 TI - Conjugated anti-TNF antibodies enhance the binding and degradation of TNF. AB - We have used disulfide-linked conjugates of murine anti-TNF antibodies to determine whether TNF binding to the cell surface could be increased by exploiting the Fc receptors present on monocytes and macrophages. Binding and degradation of TNF via Fc receptors may enhance the ability of anti-TNF antibodies to lower the high TNF levels found in several diseases. Conjugated murine anti-TNF antibodies greatly increased the binding of TNF to human U937 cells and had little effect on cells which did not express Fc receptors. U937 cells treated with anti-TNF conjugates also degraded more TNF than untreated cells. Competition analysis indicated that Fc receptors were involved in anti-TNF binding and that conjugated anti-TNF shared binding sites with monomeric anti TNF. Preincubation of anti-TNF conjugates or monomeric anti-TNF with TNF increased the amount of anti-TNF antibody bound to the surface of cells. These results demonstrate that cross-linking may greatly enhance the ability of anti TNF antibodies to mediate TNF clearance and degradation by making effective use of Fc receptors. PMID- 1305893 TI - IL-2 phase II trial in metastatic melanoma: analysis of clinical and immunological parameters. AB - Twenty-four patients with histologically proven metastatic malignant melanoma were included in a phase II trial of recombinant IL-2 (rIL-2, RU 49637). Twenty million international units (IU)/m2/day were given by continuous intravenous infusion on days 1 to 5, 15 to 18, and 29 to 31, and then monthly for 5 days until disease progression or major intolerance developed. All patients were evaluable for response and toxicity. Toxicity was consistent with one case of myocardial ischemia, 13 cases of grade III and IV hypotension, and 15 cases of proven sepsis. There were 8 objective responses: 4 of them were of short duration as they were observed on day 31 only. An activation of the immune system was detected in all patients. It was demonstrated by an increase in lymphocyte populations, especially in activated NK cells. A tendency for higher numbers of cytotoxic cells was found in patients with objective tumor responses. These results indicate a role for rIL-2 RU 49637 in treating patients with metastatic malignant melanoma. However, further trials are required to determine its optimal dosage and schedule of administration. PMID- 1305894 TI - Immunotherapy of advanced ovarian carcinomas by activation of the idiotypic network. AB - The positive effect of an immunotherapy using tumor-associated antigens or tumor cells of ovarian carcinomas has not yet been proven. Although many unique tumor associated antigens have been described and a tumor rejection could be seen in occasional cases, the failure of the immune system to destroy tumor cells is not clearly understood. An alternative approach is to initiate the idiotypic network utilizing antibodies (Ab1 or 2) against a tumor-associated antigen, which induces the production of anti-idiotypic-antibodies (Ab2 beta), mimicking the "internal image" of the tumor-associated antigen. These antibodies are able to induce a specific antitumor immunity in two ways: (1) the Ab2 can present the critical epitope in a different way and so modulates the immune system, or (2) it can induce the production of an Ab3, which by itself binds to the tumor antigen. Our first results on 22 patients with advanced ovarian carcinomas show that the induction of an anti-idiotypic antibody (Ab2 beta) against OC 125 mimicking the TAA Class III CA 125 leads to a prolongation of the survival rate also for extended stages. We see a beneficial role of the induction of the idiotypic network against a tumor-associated antigen showing delayed clinical courses of the disease after vaccination of the patients with antibody fragments of the OC 125. PMID- 1305896 TI - [In vivo and in vitro antitumoral effects of an extract from Vibrio cholerae in different murine models. II. Antitumoral effect in vitro of an extract from Vibrio cholerae: inhibition of 3LL cell growth and stimulation of murine splenocytes]. AB - A bacterial extract from Vibrio cholerae, the DGZ, has been separated into two fractions by gel filtration. The effects of these two fractions and that of the crude extract are investigated and compared by two different in vitro tests. It appears that these extracts exert direct inhibition over the growth of 3LL cultured cells and that they trigger splenocytes in vitro proliferation. PMID- 1305895 TI - [Main anticancer substances of vegetable origin]. AB - During the last thirty years, the systematic screening of thousands of vegetal extracts has led to the isolation of numerous antitumor agents which belong to various chemical series. This paper only deals with some of them which are either of current clinical use or under advanced clinical experimentation, e.g., ellipticine, homoharringtonine, camptothecine, acronycine and their derivatives. The origin, the biological activity and its mechanism, and the toxicity of each of these alkaloids are described. These examples highlight the interest of the Plant Kingdom as source of biologically active new structures and the importance of a good knowledge of the mechanism of the activity and toxicity of active components. This knowledge gives a rational basis to prepare compounds of increased activity or reduced toxicity and to use them at their best in therapeutic. PMID- 1305897 TI - [Cell-matrix interactions and odontoblast differentiation]. AB - The terminal differentiation of odontoblasts requires the integrity of the cytoskeleton and is controlled by cell-matrix interactions. These interactions implicate both matrix molecules and matrix-associated growth factors. On the one hand, predentin-dentin constituents were found to initiate odontoblast differentiation and to allow the maintenance of this state; TGF-beta or related molecules are implicated. Fibronectin on the other hand can induce the differentiation of second generation odontoblasts and interacts with three high molecular weight proteins present in membrane prepared from dental mesenchymal cells. One of these proteins (165 kDa) was localized on the surface of odontoblasts and is involved in the organization of microfilaments. Two main axes of research will have to be developed in the future in order to understand how matrix molecules and growth factors interactions can be modulated in time and space by epithelial and mesenchymal cells, and how such modulations can affect the phenotype of these cells. PMID- 1305898 TI - [Immortalization of cultured cells by the Ha-rasEJ oncogene and expression of a gene of biogenetic value]. AB - The double recombination into NIH-3T3 cells of the cloned Ha-rasEJ oncogene and the cDNA gene of the human growth hormone (hGH) under the control of a heat inducible promoter (hsp70) allowed hGH production either in vitro using the mass culture of engineered cells in biogenerators, or in vivo after xeno transplantation of the cells into an animal host. Therefore the in vivo synthesized hGH induced the production of anti-hGH polyclonal antibodies. PMID- 1305899 TI - [Bioluminescence and creation of chimeric cellular models]. AB - The response of a chimeric cellular model to a hormone has to be more specific, more sensitive, more easily measurable and quantifiable than the natural response. Hence, it can be used either in fundamental and applied studies, for example to analyse hormonal interactions, or to screen new hormone molecules. In the field of steroid hormones, we took benefit from the advantages of the firefly luciferase as receptor gene (simplicity and rapidity of the measurement, high sensitivity, handiness ...) to construct such chimaeric models. Such cell lines were obtained by developing another original use of this reporter gene based on an easy detection of the luciferase activity in intact living cells and using a photon counting camera. This was successfully adapted to obtain and to detect stable transfected cells. PMID- 1305900 TI - [Using examples of firefly luciferase gene for the study of biological activities (estrogens, retinoids, phorbol esters)]. AB - Some possible applications of chimeric cellular models, specifically responding to an effector through firefly luciferase induction are presented with the help of examples in relation with the biological activity of estradiol or retinoic acid, or phorbol ester. A comparison of experiments on either chimeric or natural responses shows that: i) the responses of both type of cellular models are effector concentration-dependent; ii) these concentrations are in the same order of magnitude; partial agonist compounds and antagonist compounds; iv) potencies (EC50) of test-compounds are similarly classified. Moreover we show that a chimeric cellular model allows the observation of interactions between hormone or effector pathways: it allows readily performed kinetic studies and long-term experiments in intact cells that permit to investigate the effect of a given effector, its reversibility and time-dependent action. Therefore, various steps of a cellular signalling pathway involved in the action of an effector may be observed with such a valuable tool. PMID- 1305901 TI - [Control of gene expression by antisense nucleic acids]. AB - The use of antisense RNA or of antisense oligonucleotides for the specific control of viral or cellular genes expression has undergone rapid developments recently; their respective advantages and drawbacks will be discussed. Progresses in oligonucleotides chemistry have lead to the synthesis of analogs with improved pharmacological properties. Besides the antisense approach, which usually targets translation initiation or splicing sites, it is possible to interfere specifically with gene expression through triple helix formation (anti-gene strategy) or through the titration of regulatory proteins (sense approach). A major problem encountered in the use of synthetic oligonucleotides is their delivery to their nuclear or cytoplasmic targets after cell uptake by an endocytic pathway; our own work in this field will be discussed. Finally, we will describe the strategies followed by our group to improve the bioavailability of antisense oligonucleotides, as for instance conjugation to poly (L-lysine) or encapsidation in antibody-targeted liposomes. PMID- 1305902 TI - [Transgenesis and gene therapy]. AB - There are now rather straightforward methods to create transgenic animals whose genome is altered at the germline level. One method consists in the micro injection of a gene into the pronucleus of a fertilized egg, the second one involves an homologous recombination event obtained in embryonic stem cells in culture. Only the latter method could eventually lead to an authentic gene therapy since it could actually substitute a normal gene for a mutated one instead of merely introducing a supplementary gene as done by micro-injection. Description of these techniques makes it obvious that germline therapy of human beings would not only be inacceptable on ethical grounds but would also hardly have any medical indications. Quite on the contrary, somatic gene therapy does not suffer from the same reservations and has numerous potential applications to man. As a matter of fact, several protocols have already received approval and have reached the stage of clinical trials: for example SCID (severe combined immunodeficiency due to a mutated adenosine deaminase gene), AIDS as well as some forms of malignant tumors. PMID- 1305903 TI - Deregulated c-fos augments the expression of IL-2 gene in T cells stimulated with anti-CD3 antibody. AB - The expression of IL-2 gene in T cells stimulated with immobilized anti-CD3 antibody is controlled by several transcription factors like as AP-1, IL-2 kappa B and NFAT. We studied an effect of deregulated c-fos, a component of AP-1, in the expression of IL-2 gene in T cells by using splenic T cells from transgenic mice carrying the exogenous c-fos gene under the control of the H2-Kb promoter (H2-c-fos). The IL-2 production of H2-c-fos T cells stimulated with anti-CD3 antibody was enhanced and prolonged. Levels of AP-1 and IL-2 kappa B transcription factors in the nuclear extract from the H2-c-fos T cells were also augmented. These results suggest that c-Fos is one of the major regulatory factors for the expression of IL-2 gene in T cells activated with anti-CD3 antibody. PMID- 1305904 TI - Effect of intra-aortic balloon pumping after cardiac surgery: comparative study of use in coronary bypass and valve replacement. AB - To compare the effects of intra-aortic balloon pumping (IABP) between use for coronary artery bypass grafting (CABG) and for valve replacement, the results were reviewed in 513 patients who underwent CABG (n = 215) or valve replacement (n = 298). The rate of weaning from IABP and in-hospital survival after IABP support were excellent in CABG patients, where all 21 CABG patients (100%) and 17 out of 25 valve replacement patients (68%) could be weaned from IABP, and 19 out of 21 CABG patients (90%) and 14 out of 25 valve replacement patients (56%) survived for a long period. From comparative studies of pre- and postoperative data, the duration of IABP support in patients who could be weaned from IABP or who achieved in-hospital survival tended to be more prolonged in patients with valve replacement than in those with CABG. Among patients having IABP postoperatively, 4 CABG patients and 8 valve replacement patients had definite indications for IABP support. In the other 34 patients, preoperatively depressed cardiac function was observed in 12 patients where most of them were patients with valve replacement. Postoperative improvements in cardiac index were not as marked in patients undergoing valve replacement with IABP. The outcome for patients who had definite causes of post-operative cardiac failure, which were more numerous in the valve replacement group, was poor even if they could be weaned from much longer IABP support. In conclusion, the IABP was more effective in patients with CABG compared with those with valve replacement, because the number of patients who had a depressed cardiac function during the pre- and postoperative periods was lower in the CABG group and the incidence of serious perioperative complications was less frequent in these patients. PMID- 1305905 TI - Ultrastructural studies of the bile duct in alcoholic liver disease. AB - The fine structural characteristics of the bile duct in patients with alcoholic disease are described. Dark cell metamorphosis, edematous microvilli, and increased number of pinocytotic vesicles on the basal wall surface of the duct epithelium were observed. These alterations may be interpreted as evidence of disordered water metabolism, probably reflecting secretion and reabsorption hyperfunction in the duct epithelium. In addition, widened intercellular spaces in the basal half of the epithelium suggested retention of fluid following reverse pinocytosis along the lateral cell surface. Although no alterations of the duct epithelium distinct from those in patients with other liver diseases were apparent in patients with alcoholic liver disease, the basement membrane of the bile duct exhibited unusual duplication with multiple layers and occasional loop-formation in lacunae on the basal surface. PMID- 1305906 TI - Effects of angiotensin II on regional brain noradrenaline metabolism in non stressed and stressed rats. AB - By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4 hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in various rat brain regions, the effects of angiotensin II (AT II) injected intracerebroventricularly (ICV) were investigated in non-stressed and stressed rats. Immobilization stress with a wire mesh was employed. Immobilization stress induced significant increases in MHPG SO4 levels in all brain regions examined, i.e., hypothalamus, amygdala, thalamus, midbrain, hippocampus, cerebral cortex and locus coeruleus (LC) region, which suggests that stress increases NA release in these regions. AT II (1 and 10 micrograms), injected ICV 5 min before exposure to stress for 60 min, attenuated stress-induced increases in MHPG-SO4 levels in the hypothalamus, thalamus and amygdala. AT II, injected ICV in non-stressed rats at 65 min before sacrifice, significantly elevated MHPG-SO4 levels in the midbrain, cerebral cortex, thalamus and LC region. These results indicate that the attenuating effect of AT II on stress-induced increases in brain NA release are, in part, related to the reduction of fear and/or anxiety of the animals exposed to stress. PMID- 1305907 TI - Myocardial ischemia in Kawasaki disease; evaluation by dipyridamole stress thallium-201 (Tl-201) myocardial imaging and exercise stress test. AB - The detection of myocardial ischemia is essential for evaluation of patients with Kawasaki disease, especially who have had coronary artery lesions. To evaluate the clinical efficacy of Tl-201 single photon emission computed tomography (SPECT) after dipyridamole infusion (maximum dose 0.70 mg/kg) for detecting myocardial ischemia, 44 patients with Kawasaki disease aged 7.7 +/- 4.8 years at the study and 10 age matched controls were observed. In the Kawasaki disease group, significant coronary artery stenosis was observed in 14, coronary aneurysm without stenosis in 18, the regression of the coronary aneurysms in 2 and without coronary lesions in 10 patients. In 22 of 44 patients, treadmill exercise stress test was also performed at the same period. Myocardial ischemic changes were observed in 11 patients, all combined with significant coronary artery stenosis. The sensitivity of SPECT for detection of overall coronary stenosis was 79%, contrary that of treadmill exercise test was only 33% (p < 0.001). Furthermore, among the patients having significant coronary stenosis, the severity score was significantly elevated in patients who had electrocardiographic abnormal Q wave compared to those without abnormal Q wave (51.0 +/- 38.8 versus 20.0 +/- 12.1, p < 0.05). These data suggest that the pharmacological stress scintigraphy using dipyridamole injection provides not only the accurate detection but quantitative evaluation of myocardial ischemia in these patients. This noninvasive technique may become one of the most useful index for detection and follow-up of myocardial ischemia in Kawasaki disease. PMID- 1305908 TI - Concentrations of interleukin-1 beta, interleukin-6, interleukin-8 and TNF-alpha in cerebrospinal fluid from children with septic or aseptic meningitis. AB - Cytokines at an inflammatory site may be a better indicator of the clinical severity of an infectious disease than the serum levels of the cytokines. Concentrations of interleukin-1 beta (IL-1 beta) in paired samples of cerebrospinal fluid (CSF) from 10 rabbits with experimental bacterial meningitis caused by H. influenzae type b, were measured, and compared to the concentrations of four cytokines; IL-1 beta, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in CSF samples from 45 children with or without meningitis. The IL-1 beta concentrations in the CSF from rabbits with experimental meningitis were significantly higher than the concentrations in control animals without meningitis (p < 0.001). The mean CSF concentrations of IL 8 from meningitic children were significantly higher than in the control group without meningitis (p < 0.005). TNF-alpha was only detected in septic meningitis. Assays of IL-6, however, were not significantly different in the septic meningitis group, the aseptic meningitis group and the non-meningitis group. These data indicate a possible role of IL-1 beta, IL-8 and TNF-alpha as mediators in the meningeal inflammatory process in patients with meningitis and TNF-alpha, in particular, may play a role in the pathogenesis of septic meningitis. PMID- 1305909 TI - Clinical significance of thallium-201 single-photon emission computerized tomography (Tl-201 SPECT) in the evaluation of viability of gliomas. AB - The clinical significance of Thallium-201 single-photon emission computerized tomography (Tl-201 SPECT) in the evaluation of viability of gliomas was studied comparatively with histological examination of tumor tissue using Ki-67 and proliferative cell nuclear antigen (PCNA) monoclonal antibody. The relationship between radionuclide uptake of Tl-201 in tumor specimens and labeling indices of special staining using Ki-67 and PCNA monoclonal antibodies were also studied. The population studied consisted of 17 patients with glioma. Tl-201 indices obtained from early and delayed images and its washout rates were used for quantitative analysis of Tl-201 SPECT findings. Tl-201 indices showed high values according to the histological malignancy of gliomas. Radionuclide uptake of Tl 201 in the tumor specimens were also high in those with high labeling indices of Ki-67 and PCNA. The lesions with marked Tl-201 uptake on early and delayed images had numerous Ki-67 and PCNA positive-stained cells. The lesion with low Tl-201 washout rate therefore reflected well the more viable lesion in the tumor tissue. It is concluded that the viability of gliomas including anaplastic changes and response of gliomas to the treatment can be detected by serial study with Tl-201 SPECT. PMID- 1305910 TI - Comparison of incidence, mortality and treatment of acute myocardial infarction in hospitals in Japan and China. AB - Acute myocardial infarction (AMI) is one of the most intractable diseases and is increasing rapidly in Japan and China. Two hospitals in Japan and China, the Critical Care Center of Kurume University Hospital and the Chinese Beijing 309 Hospital in China (abbreviated to Beijing 309 Hospital) were compared. The incidence, mortality and treatment of AMI were investigated in both hospitals from 1989 to 1991. The incidence of AMI for all patients admitted during the three years was 5% in Kurume University Hospital and 4.7% in Beijing 309 Hospital, which are similar rates. The average age of the patients in Beijing 309 Hospital was younger (58 +/- 13) than in Kurume University Hospital (64 +/- 11). The mortality rate in Kurume University Hospital was slightly lower than the rate in Beijing 309 Hospital (8.1% vs 8.9%). Thrombolytic therapy was actively performed in both hospitals. In Kurume University Hospital, urokinase (UK: 71.4%) or recombinant tissue plasminogen activator (rt-PA: 28.6%) was administered by intravenous (85.7%) and intracoronary percutaneous transluminal coronary recanalization (PTCR: 14.3%) injection. In Beijing 309 Hospital, UK (32.7%) or snake poison enzyme (SPE: 62.3%) was administered by intravenous (85.8%) or intra aortic (14.2%) injection. Rt-PA was only used in Japan and SPE was only used in China, but both had very strong fibrinolytic effects and resulted in high success rates of coronary reperfusion. The incidence of direct coronary intervention with percutaneous transluminal coronary angioplasty (PTCA) and intra-aortic balloon pumping (IABP) for cardiogenic shock was much higher at Kurume University Hospital than at Beijing 309 Hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1305912 TI - Non-invasive evaluation of pulmonary arterial and right ventricular pressures with contrast enhanced Doppler signals of tricuspid regurgitation flow using sonicated albumin solution. AB - To determine the feasibility of the non-invasive determination of systolic pressure of the pulmonary artery and the right ventricle in pediatric patients, the velocity of tricuspid regurgitation was measured in 30 patients using a contrast enhanced Doppler echocardiography. After sonicated albumin injection, trivial tricuspid regurgitation signals were enhanced in 27 patients (90%). Peak systolic velocity was not altered by before and after sonicated albumin injection in 2 patients. Right ventricular (RV) systolic pressure obtained by continuous wave Doppler during sonicated albumin enhancement corresponded very closely to that measured by catheter in 27 patients (r = 0.96). In 27 patients, difference of estimation of RV systolic pressure by non-enhanced Doppler and enhanced Doppler with sonicated albumin was statistically significant (32.3 +/- 27.6 mmHg versus 2.9 +/- 7.7 mmHg p < 0.001). Systolic pressure of pulmonary artery was estimated by RV systolic pressure measurement (by enhanced Doppler method) minus peak pressure gradient across the pulmonary valve (non-enhanced Doppler method). Pulmonary arterial systolic pressure measured by enhanced Doppler method and that by catheter method were highly significant (sonicated albumin method, r = 0.95). This technique may be a valuable non-invasive method for determining an accurate right ventricular and pulmonary arterial systolic pressures in this setting. PMID- 1305911 TI - A study of the role of sex hormones in rat ovarian cancer. AB - The effects of estrogen, progesterone, and testosterone on the growth of 7,12 dimethylbenz(a)anthracene (DMBA) induced adenocarcinomas in rats (Wistar strain) were evaluated. Estrogen resulted in the highest acceleration of tumor volume. The histologic features were a solid structure associated with a significant proliferation of connective tissues and with many signet ring cells with intracytoplasmic canaliculi. Progesterone changed the histologic features to a more immature adenocarcinoma associated with a notable solid area with many mitotic figures, although the growth rate of the tumor was the same as the controls. On the contrary, testosterone induced the slowest tumor growth and a histologically scirrhus pattern. The results of this preliminary observation indicate a possible role for sex steroids in the ovarian tumorigenic process. PMID- 1305913 TI - Contribution of GTP-binding protein to the actions of endothelin-1 on rabbit parasympathetic neurons. PMID- 1305914 TI - Monosynaptic input to deep dorsal horn neurons from primary afferent A delta fibers in the rat spinal cord in vitro. PMID- 1305915 TI - [Strains of Salmonella with atypical biochemical activity found in diagnostic material]. AB - Biochemically atypical strains belonging to 11 genera of Salmonella subspecies I in the number of 200 were collected in Poland in the years 1980-1991 were tested by means of 22 biochemical tests. Atypical property stability was detected in 164 strains. Most stable properties were following: ability to ferment lactose, lack of ability of dulcitol fermentation, lack of hydrosulfide production and lack of lysine decarboxylation. Atypical properties were occurring singularly or clusters numbering two or three. Identification procedure for Salmonella accepted in this country enables proper diagnosis of an atypical strain, however it requires application of supplemental biochemical tests. These strains were tested for susceptibility of 15 antimicrobial agents and no correlation between antibiotic resistance and occurrence of one or several atypical properties has been found. PMID- 1305916 TI - [A trial application of the latex test for evaluation of antibody level in rabbit immune sera]. AB - A latex test was elaborated which served for evaluation of quality of rabbit immune sera for antigen 0 of selected Gram-negative bacteria. Sensitivity and specificity of this test in comparison with passive hemagglutination and immunoenzymatic DOT-ELISA reactions was evaluated. These studies were performed on immune sera for antigen O of Salmonella groups B, C1, C2, D and E, Yersinia pseudotuberculosis and in antigen preparations for above listed microorganisms both in homologous and heterologous systems. It was found that sensitivity of the latex test is 9 to 160 times lower than that of passive hemagglutination and 7 to 307 lower than for DOT-ELISA. Sensitivity of the latex test and passive hemagglutination reaction was evaluated on the basis of results of cross reaction between studied antigens and unabsorbed rabbit sera, establishing so called sensitivity indexes, which were informing how many times heterologous titer is lower than homologous titer. So evaluated sensitivity of the latex test was close to sensitivity of the passive hemagglutination reaction. It was found that slide latex test is characterized by satisfactory sensitivity and good sensitiveness and may be used for evaluation of antibody level 0 antigens of Salmonella and Yersinia. The value of this test is characterized by high repeatability of results, as well as low work and time-consuming. PMID- 1305917 TI - [Investigation of factors determining stability of BCG vaccine]. AB - This study was aimed at establishment of influence of a carrier-sodium glutamate and of changes introduced during the process of freeze-drying on survival of BCG bacilli during lyophilization, as well on thermostability and homogeneity of the vaccine and its immunogenicity. It was found that appropriate drying of the vaccine after freeze-drying performed in higher temperature influences favorably its thermostability. Concentration of the carrier is significantly influential for survival of bacilli during freeze-drying. Vaccine containing 1% of sodium glutamate was characterized by best thermostability, homogeneity and high survival of bacilli during freeze-drying. These parameters were keeping on a high level also one year after expiration date. It was shown that there exists a proportional dependence between immunogenicity of the vaccine measured indirectly by intensiveness of tuberculin allergization and number of live particles of BCG contained in vaccination dose. PMID- 1305918 TI - [Dependence between penetration route and course of infection with Coxiella burnetii in mice]. AB - This study was aimed at investigation of course of Coxiella burnetii infection in mice infected by these bacteria by different routes. The animals infected intranasally, perorally, intraperitoneally and intravaginally by suspension of C. burnetii cells. Mice were also infected via peritoneal and intravaginal route with spermatozoa derived from infected males. In all animals at the same time specific antibodies against phase I and phase II antigens of C. burnetii belonging to IgG and IgM classes of similar titers appeared and this was detected by dot-blot immunoenzymatic test. Independently of route of infection C. burnetii were present in the liver, spleen, testicles, prostate and spermatozoa of tested animals. The bacteria were detected in these organs for 18 days of infection, in the blood for 7 days only, whereas in urine they appeared as late as 14 days after infection. The course of infection with C. burnetii in mice in thus similar regardless of site of bacterial penetration. Infection with C. burnetii may be also transmitted by a sexual route from male to female animals. Infection of female mice occurs both after intravaginal application of live suspension of C. burnetii or spermatozoa derived from infected males. PMID- 1305919 TI - [Occurrence of infections with C burnetii (Q fever) in persons from increased risk groups in Poland--serological survey and evaluation of studied methods]. AB - During years 1988-1991 at Regional Sanitary and Epidemiological Stations in Bialystok, Kielce, Lublin, Leszno, Piotrkow Trybunalski, Lodz, Poznan, Plock, Opole, Sanok, Skierniewice and Zielona Gora--serological studies in persons amenable to compulsory check-up against brucellosis were performed for detection of infections with C. burnetii. In whole, 20651 persons were investigated on the Polish territory and it was found that in 22.8% antibodies against antigens of C. burnetii are present. Percentage of persons with detected antibodies varied in different regions from 0 to 41.7%. No antibodies were found in persons inhabiting regions of Kielce, Piotrkow Trybunalski and Skierniewice. Most persons with antibodies indicating contact with C. burnetii were found in West Poland, namely in the Leszno and Poznan region. As in diagnosis of Q fever two methods (OWD and OMA) or OWD only were applied, it is difficult to compare results obtained in regions using two or only one method of determination. PMID- 1305920 TI - [Evaluation of usefulness of OWD and OIEP in diagnosis of epidemically occurring infections caused by Mycoplasma pneumoniae]. AB - Blood serum samples of 3593 persons clinically suspected of infection with Mycoplasma pneumoniae were tested. Of these, patients with pneumoniae constituted 66.5%, upper respiratory tract infection--24.0% and with symptoms localized outside the respiratory system--9.5%. These studies were performed by application of complement fixation test (OWD) and immunoelectroprecipitation (OIEP) methods, accepting as a diagnostically significant--titer 1:60 or higher and/or occurrence in OIEP reaction with serum diluted 1:2 or more. Among patients studied prevailed children in the age of 3 to 16 years (61.6%). Mycoplasmosis was detected in these patients in 1071 out of 2236 cases (47.9%). Compatible results in both tests were obtained in 90.6% patients, whereas OWD only in 3.0% and OIEP only in 6.4% cases. Simultaneous application of both tests increased detectability of infections caused by M. pneumoniae by 3% in relation to OIEP and by 6.4% in relation to OWD. PMID- 1305921 TI - [Influence of high dose intravenous immunoglobulins (IVIG) on HSV-1 infection in immunosuppressed mice]. AB - Influence of low and high doses of intravenous immunoglobulin (IVIG) was compared on the basis of survival studies of mice infected with temperature sensitive (ts 28 degrees C) clone of Herpes simplex virus (HSV-1) after previous treatment with cyclophosphamide (CY), Sandoglobulin containing intact IgG and Gamma-Venin containing only fragments of (Fab)2 IgG were used. It was found that 4 and 16 mg doses protected animals in contrast to the 32 mg dose of Sandoglobulin which protected mice in only small degree. PMID- 1305922 TI - [Changes in the level of humoral response for measles virus in patients with subacute sclerotic panencephalitis during 1984-1989]. AB - Immunological response to measles virus in serum and cerebro-spinal fluid of 338 patients with subacute sclerotic panencephalitis (SSPE) during the years 1984 1989, was investigated. It was found that mean titer and distribution of results of antibody determination by the hemagglutination inhibition (OZHA) method in patients sera are visibly differing during consecutive years of investigation. Analysis of these parameters in determination by the immunoenzymatic methods (ELISA) has shown their higher stability. Also results of determinations of IgG concentration in sera of patients with SSPE did not demonstrate significant differences between consecutive years of investigation. Systematic decrease of mutual relation between antibodies to measles virus detected by ELISA and OZHA was found. Analysis of local synthesis of antibodies to measles virus in the central nervous system has revealed that it most strongly expressed by hemagglutinin. PMID- 1305923 TI - [Use of western blotting methods in diagnosis of viral infection causing tick borne encephalitis]. AB - A Western blot method for investigation of antigens and of immunological response to tick-borne encephalitis was prepared. An analysis was performed testing cross reactions of proteins of prepared antigen with sera for four Polish strains of tick-borne encephalitis and four other flaviviruses. Usefulness for diagnosis of infections in humans was determined by comparison of Western blot method with ELISA immunoenzymatic test. It was found that elaborated method permits equally as ELISA for evaluation of immune response in immunoglobulin classes. By evaluation of response for individual virus components, Western blot method enables at the same time verifications of nonspecific determinations which result from reaction of antibodies present in tested diagnostic materials with nonviral antigens. PMID- 1305924 TI - [Evaluation of contents of A and B group substances in biological preparations]. AB - The study was aimed at determination of blood A and B group substances in biological preparations used in Poland. Twenty three series were investigated, namely: Di-Te-Per, Ty-Te, Ty, Te, against cholera, vaccine according to Delbet and Panodin. Also were tested: 65 series of imported preparations of immunoglobulin g (i.v.) such as Endobulin, Sandoglobulin, Gamma-Venin, Veinoglobuline and 5 local series such as Bioglobulin, as well as 9 series of preparation LNI (i.m.) Human Gamma Globulin. Presence of substance A was detected in tetanus and botulinum horse antitoxins in amount from 3.75 micrograms/ml to 30 micrograms/ml. Group substances A and B contained 6 series of LNI preparations Veinoglobuline. Amount of substance A was detected as 3.75 micrograms/ml-7.5 micrograms/ml and of substance B as 2,5 micrograms/ml-5 micrograms/ml. Group substances A and B were not present in vaccines used according to vaccination calendar. PMID- 1305925 TI - [Investigation of immunogenic properties of diphtheria antitoxin by intradermal active test of potency]. AB - Usefulness of four variants of intradermal test for routine testing of protective potency and diphtheria anatoxin was studied. Comparing with classical active test it was found that full intradermal test possesses data system and results comparable to the classic test and may replace it. This in effect results in four fold reduction of guinea pig number necessary for performance of the investigation. As orientating test, estimate determining AnaDi potency a single dose performed on six guinea pigs was selected. In the intradermal test the time of investigation, as compared with the classic test, may be shortened by one week. PMID- 1305926 TI - [Simplified active test of estimating tetanus toxoid]. AB - The main purpose of these investigations was the comparison of two potency tests of Tetanus Toxoid. It was found that two doses test with reduced number of animals can be used in assay of different vaccines containing Tetanus component. One dose test is agreeable with requirements of WHO. It is credible and not complicated method of estimation Diphtheria and Tetanus Toxoids. This test required minimal number of animals. PMID- 1305927 TI - [Investigation of activity of new quaternary imidazole-linear chlorides against selected bacterial strains. Synthesis of 2-alkyl-3-alkymethyl-1 ethylimidazolelinear and 2-alkyl-3-alkoxymethyl-1-ethylimidazolelinear chlorides]. AB - Synthesis and bacteriostatic properties of a new alkylthiomethylimidazole-linear and alkomethyly-limidazole-linear chlorides was described. It was found that these chlorides are active against bacilli, cocci and yeast-like fungi and express lower activity against rods. Highest activity was observed with 2-benzyl 3-decyloxymethyl-1--ethylimidazolinear and 1-ethyl-heptadecyl-3 undecyloxymethylimidazolelinear chlorides. PMID- 1305928 TI - [Evaluation of susceptibility to antibiotics of Staphylococcus aureus strains resistant to methicillin]. AB - Methicillin-resistant strains of Staphylococcus aureus (MRSA) constitute a serious diagnostic and therapeutic problem. Over 500 strains of Staphylococcus aureus were tested for susceptibility to methicillin. By application of a screening method, 13.7% of these strains were classified as methicillin resistant. Over 95% of these strains were isolated from hospital infections. Applying criteria of belonging of these strains to methicillin-resistance classes it was found that 49.3% belonged to class II, 31.2% to class III and 19.5% to class IV. Analysis of susceptibility to antibiotics of MRSA strains demonstrated significant differences between class II and between class III and IV in resistance to imipenem, gentamycin, erythromycin and tetracycline. All tested strains were susceptible to ciprofloxacin, ofloxacin, vancomycin and teicoplanin. The screening method (25 mg methicillin/l of TSA medium) results in obtaining of univocal results of determination of methicillin-resistance in S. aureus. PMID- 1305929 TI - Midwives step out of the shadows. 1991 Sir William Power Memorial Lecture. PMID- 1305930 TI - The last of the handywomen. PMID- 1305931 TI - The independent midwife: has she a role to play in our society? PMID- 1305932 TI - Students' attitudes and motivation towards midwifery education and training. PMID- 1305933 TI - The diploma in professional studies in midwifery/advanced diploma in midwifery by distance learning. PMID- 1305934 TI - The diploma in profession studies in midwifery/advanced diploma in midwifery by distance learning. Learning at a distance. PMID- 1305935 TI - Personal professional profiles. PMID- 1305936 TI - Sudden Infant Death National Conference. PMID- 1305937 TI - Emotional and mental disturbances of the puerperium. PMID- 1305938 TI - Sudden infant death syndrome. Part 1. Definition and classification of SIDS. PMID- 1305939 TI - Maternal mental health: "falling between two stools". PMID- 1305940 TI - Sudden infant death syndrome. Part 2. Possible causes of SIDS. PMID- 1305941 TI - Toxoplasmosis. PMID- 1305942 TI - Congenital toxoplasmosis--a case study. PMID- 1305943 TI - The maternity services report. PMID- 1305944 TI - A woman's touch--mothers identify babies by fingertip contact alone. PMID- 1305945 TI - Free speech. Scottish skills. PMID- 1305946 TI - Midwifery in Canada. PMID- 1305947 TI - Workshops: a stimulus for change. PMID- 1305948 TI - WHO baby-friendly hospital initiative: a worldwide commitment. PMID- 1305949 TI - Daring to care for women at risk. A report on the WHO safe motherhood initiative: educational project. PMID- 1305950 TI - Territorial boundaries in childbirth. PMID- 1305951 TI - HIV and breast-feeding. PMID- 1305952 TI - Quality: who says what? The 11th Dame Rosalind Paget Memorial Lecture. PMID- 1305953 TI - Who cares for the carers? The Nurses' Welfare Service. PMID- 1305954 TI - Antenatal care towards the year 2000. PMID- 1305955 TI - Free speech. You name it--we'll try it. PMID- 1305956 TI - Changes in the rat brain 5-HT1A and 5-HT2 receptors after chronic administration of levoprotiline, (+)-oxaprotiline and other antidepressant drugs. AB - The effects of levoprotiline (LEV), a (-)-enantiomer of oxaprotiline (OXA) and a clinically effective antidepressant, on the binding parameters of hippocampal 5 HT1A and cortical 5-HT2 receptors of rats were compared with those of (+) enantiomer of OXA ((+)-OXA), imipramine and mianserin. Both LEV and (+)-OXA displayed in vitro some affinity for 5-HT1A receptors labelled with [3H]-8-OH DPAT, and for 5-HT2 receptors labelled with [3H]-ketanserin. Repeated administration of LEV, for 14 days led to a marked increase in the number of 5 HT1A binding sites in the rat hippocampus, with no change in the KD values. (+) OXA, imipramine and mianserin produced similar effects on 5-HT1A binding parameters. The number of 5-HT2 receptors was increased after two weeks of LEV administration, not altered after (+)-OXA, and decreased after imipramine or mianserin. The number of [3H]-ketanserin binding sites was decreased after four weeks of (+)-OXA administration, but not altered after LEV. The specific binding of [3H]-ketanserin in the rat cerebral cortex was decreased after repeated treatment with LEV and (+)-OXA (ex vivo). In competition studies the affinity of serotonin for [3H]-ketanserin binding sites was decreased in LEV- and increased in (+)-OXA-treated rats. The results suggest that LEV similarly to other antidepressants increases the number of 5-HT1A receptors, however without common alteration in 5-HT2 receptor number and function. PMID- 1305957 TI - Synthesis, physicochemical and preliminary pharmacological properties of N-[beta hydroxy-gamma-(N-phenylpiperazinepropyl)]-2-pyrrolidinone. AB - The present paper reports on the synthesis and preliminary pharmacological properties of N-[beta-hydroxy-gamma-(N-phenylpiperazinepropyl)]-2- pyrrolidinone (MG-1). MG-1 was obtained by aminolysis of 1-(beta, gamma-epoxypropyl)-2 pyrrolidinone and N-phenylpiperazine. Its structure was established by elemental and spectral analyses (IR, UV, MS, 1H, 13C, 2D H-H and 2D C-H NMR). The antiarrhythmic activity of MG-1 was investigated on mice, rats and guinea pigs, using several models of arrhythmia. MG-1 attenuated or prevented the adrenaline- and barium chloride-induced arrhythmia. MG-1 demonstrated potent local anesthetic properties and depressed the depolarization phase of the action potential of cardiac cells. These results indicate that MG-1 possesses antiarrhythmic activity. PMID- 1305958 TI - Propranolol analogs containing natural monoterpene structures: synthesis and pharmacological properties. AB - A few derivatives of natural, bicyclic monoterpenes, which are propranolol analogs, were synthetized. Those compounds were studied pharmacologically in order to determine their toxicity, antiarrhythmic activity in selected experimental models of arrhythmia, the local anesthetic effect and influence on the cardiovascular system. The tested compounds showed a less potent or similar toxicity towards reference drugs, were devoid of an antiarrhythmic activity in the model of barium arrhythmia, yet some of them (compounds 9 and 12) increased the arrhythmogenic dose of strophanthin. All the compounds studied had a local anesthetic effect stronger than lidocaine in infiltration anesthesia, and compound 8--also in surface anesthesia. PMID- 1305959 TI - Structure-activity relationship studies of CNS agents. Part VIII. Bulk tolerance around the protonation center of 4-substituted 1-(3-chlorophenyl)piperazines at 5 HT1A and 5-HT2 receptors. AB - The effect of a steric hindrance around the protonation center of the model 4 substituted 1-(3-chlorophenyl)-piperazines 1-9 and 11-14 on their affinity for 5 HT1A and 5-HT2 receptor sites was investigated. Additional evidence for hydrophobic interactions between the N-4 hydrocarbon substituents and 5-HT1A receptors has been presented. However, the hydrophobic forces play a minor role in stabilization of the bioactive complex with 5-HT2 receptors. It has also been found that even bulky substituents around the protonation center of 1-aryl piperazines are well tolerated at both 5-HT1A and 5-HT2 sites. PMID- 1305961 TI - Circadian changes of cytochrome P-450-dependent monooxygenase system in the rat liver. AB - Circadian changes in cytochrome P-450 and cytochrome b5 content and activity of NADPH-cytochrome P-450 and NADH-cytochrome b5 reductases have been studied in rat liver microsomes in season autumn. The obtained results indicate, that cytochrome P-450 in 6-month-old animals shows 12 h rhythm, but in older ones 24 h rhythm. NADPH-cytochrome P-450 reductase activity shows 24 h rhythm in oldest animals only. Cytochrome b5 and its reductase has 24 h rhythm in all examined groups of rats. PMID- 1305960 TI - The role of GABA-ergic signal in the regulation of melatonin biosynthesis in vertebrate retina. AB - The in vivo effects of GABA-ergic drugs on the activity of serotonin N acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), two enzymes involved in melatonin biosynthesis, were investigated in light-exposed chicken retina. The ip administration of muscimol and baclofen (direct agonists of GABA-A and GABA-B receptors, respectively), aminooxyacetic acid (an inhibitor of GABA transaminase), and nipecotic acid (an inhibitor of GABA reuptake), significantly increased the retinal NAT activity by 50-100%. Similar rises in NAT activity were observed following intraocular treatment of ether-anesthetized chickens with muscimol, baclofen and GABA. In contrast to NAT, there was no effect of the tested drugs on the retinal HIOMT activity. Aminophylline (a phosphodiesterase inhibitor) markedly elevated the retinal NAT activity, and a combined treatment with the GABA-ergic drugs and aminophylline resulted in additive effects. The actions of both muscimol and baclofen were antagonized by picrotoxin and bicuculline (two GABA-A receptor blockers), whereas the effect of baclofen was not changed by a selective GABA-B receptor blocker, CGP 35,348. Melatonin given ip significantly raised NAT activity, and its combination with muscimol further stimulated the enzyme. Picrotoxin and bicuculline given to chickens during the dark phase of 12 h light--12 h dark illumination cycle significantly suppressed the nocturnal NAT activity in retina. Neither GABA nor muscimol and baclofen significantly affected basal and forskolin (1 microM) stimulated adenylate cyclase activity in vitro in light-exposed chicken retina. It is concluded that a GABA signal (acting through type A of GABA receptors) plays an important role in a complex mechanism regulating the rhythmic melatonin biosynthesis in vertebrate retina. PMID- 1305962 TI - Circadian variations of phenacetin metabolism in rats in vivo and in vitro. AB - The metabolism of phenacetin in vivo and in vitro at different periods of day was investigated in rats. In rats maintained on standard LD conditions the disappearance rate of phenacetin from blood and activity of phenacetin O deethylase in liver were the highest in the morning and the lowest in the evening. Continuous illumination, adrenalectomy, phenobarbital or proadifen abolished this difference. It is postulated that these circadian changes of microsomal metabolism of phenacetin in rats liver are not fully responsible for the rhythmical changes in the antipyretic action of this drug that was observed previously. The mechanisms of this phenomenon are discussed. PMID- 1305963 TI - Circadian changes in the elimination of amitriptyline in rats. AB - The circadian changes in elimination and absorption of amitriptyline after its intravenous and intragastric administration in rats were investigated. The values of such parameters as: AUC, MRT, t1/2, Cl, Vd, k(a) for amitriptyline change in the circadian rhythm. The fastest elimination of amitriptyline was observed in the dark phase (the acrophases for clearance were ca. 11 p.m. for iv administration and ca. 10 p.m. for po administration). The maximal value of clearance corresponds to the minimal values of MRT and t1/2. The acrophase for the constant absorption rate (po) falls at 7 p.m. Cyclic changes were not observed as far as the bioavailability is concerned. PMID- 1305964 TI - [Effect of different vascular prosthesis materials on blood platelets, blood clotting and fibrinolysis]. AB - Studies were performed on Dacron vascular prostheses (USA), Gore-Tex (Germany), polyester prostheses (Czechoslovakia), Lawsan (Russia), as well as on DALLON standard and DALLON-double velour prostheses (Poland), non-impregnated or impregnated with collagen, with heparin and albumin, with antithrombotic and antibacterial preparation, and with antibacterial preparation. In vitro, all the materials of vascular prostheses cause an adhesion of platelets in different degree, increase the availability of platelet factor 3, release platelet factor 4, reduce the blood clot retraction, shorten clotting time of the whole blood as well as recalcination time of intact plasma and increase the prothrombin consumption. None of the materials induced platelet aggregation nor influenced the activity of fibrinolytic system. Prostheses impregnated with collagen or with heparin and albumin were the most thrombogenic. Those impregnated with antibacterial preparation or with antibacterial and antithrombotic preparations, and Gore-Tex prostheses showed the lowest thrombogenicity. Thrombogenicity of vascular prostheses not only depends on chemical structure of the material, but on the method of fibre manufacturing by individual producers as well. PMID- 1305965 TI - [Changes in the activity of the clotting system and fibrinolysis components in the layers of double velour DALLON grafts at different periods after implantation into the aorta]. AB - During one year experiment, the thromboplastic, antiheparin, plasminogen activator, antithrombin and antiplasmin activities were evaluated in the homogenates of the intimal, medial and adventitial layers of polyester double velour DALLON prostheses implanted into the dog abdominal aorta. It was found, that 7 days after implantation the thromboplastic, antiheparin and plasminogen activator activities in DALLON graft neointima were high, whereas those of the antiplasmin and antithrombin were low. These changes facilitate the sealing of the prosthesis pores and at the same time prevents thrombosis. Four months after implanting, the activity of hemostatically active components in the various graft layers became similar to the activity of aorta components. Rapid decrease of the thrombogenic potential and increase of the fibrinolytic activity in layers of double velour DALLON grafts facilitate the maintenance of graft patency. PMID- 1305967 TI - [Comparison of cathepsin D activity of DALLON-standard and DALLON-double velour grafts implanted into the abdominal aorta]. AB - Cathepsin D activity was compared during the healing period of polyester DALLON standard and DALLON-double velour prostheses implanted into the abdominal aorta of dogs. During first months following the implantation cathepsin D activity is considerably higher in all the layers of both types of prostheses than in the aorta. The normalization of this enzyme activity occurs significantly faster during the healing of DALLON-double velour prostheses than in that of DALLON standard. This fact shows greater progress in the protein metabolism normalization during the process of healing and tissue reconstruction in DALLON double velour prostheses. PMID- 1305966 TI - [Comparison of healing characteristics of DALLON-standard and DALLON-double velour vascular prostheses]. AB - By means of histological method and the scanning and transmission electron microscope healing processes of two types of Polish prostheses: DALLON-standard and DALLON-double velour were compared. The experiments were carried out on 36 dogs. The two types of prostheses mentioned were implanted in abdominal aorta. The grafts were removed 1, 4 and 12 months after implantation. The performed studies showed that although the sequence and nature of morphological changes leading to the reconstruction of the vascular wall in both types of grafts were similar, the development of the neointima as well as the formation of the neo adventitia firmly accreted with surrounding tissues were considerably faster in double velour DALLON prostheses. Unlike in standard DALLON prostheses, the neointima of double velour DALLON grafts was rich in cells, had elastic fibres. Already after 12 months double velour DALLON grafts were completely covered by endothelial cells, which proves better reconstruction of the vascular wall. Rapid endothelial cells coverage of the lumen surface prevents thrombosis. Morphological differences observed in endothelial cells covering the neointima of standard grafts and double velour graft suggest the existance of various sources of endothelialization in both types of grafts. PMID- 1305968 TI - [Content and distribution of collagen in aorta double velour DALLON grafts]. AB - The aim of the study was to determine the collagen content, distribution and quantitative ratios between main types of collagen (found in normal vascular walls) in various layers of double velour DALLON grafts at different periods after implantation. Double velour DALLON prostheses were implanted into the abdominal aorta of 24 dogs. These grafts were excised 7 days, 1, 4 and 12 months after implantation and together with normal arteries, after dissection into intimal, medial, and adventitial layers, tested for their hydroxyproline content. Type I, III, V collagen was also determined (fractionation of pepsin digestion products). Already 7 days after implantation collagen appeared in all the newly formed layers of the grafts. With the passage of time after the operation collagen content was gradually increasing. After 12 months collagen content in the intimal and adventitial layers was significantly higher than in normal arterial wall. Approximate quantitative ratio between collagen types I, III and V in all graft layers was 7:2:1 and did not change during the 1-year-observation. Rise in collagen content results in graft wall stiffening, and the presence of III type collagen increased platelet-aggregating activity. Both these factors created a tendency to the formation of thrombosis in the graft. PMID- 1305969 TI - [Attempts at modification of the polyester vascular prosthesis]. AB - Polyester vascular bilaterally velour prostheses produced by the Enterprise of Medical Products TRICOMED in Lodz were modified through: putting negative electric charge on the internal surfaces of prostheses; additional cleaning with ethanol; covering of the surfaces of prostheses with silicone preparation; two sided covering of the surfaces of prostheses with collagen by the radiative method; covering of the surfaces of prostheses with chitosane. Laboratory investigations, investigations of hemolytic and toxic effects of aqueous as well as experimental investigations has been carried on piglets. During these investigations it was observed that the carried preparations caused multiple increase of electrical conductivity of proper and dry remnant after evaporation of the aqueous extracts. Hemolytic and toxic effects were not observed. In radiological and pathomorphological investigations it was observed that none of the preparations used for modification of vascular prostheses influenced improvement of their biological properties. In comparison with the initial prostheses DALLONR these prostheses evoked a greater reaction of tissues which was manifested with a thick internal layer causing narrowing of the lumen of the section with prosthesis or closing it. A small improvement of the biological properties of the prostheses were achieved after cleaning them with methanol. However, this improvement is so small that it does not justify changes in the existing technology. PMID- 1305970 TI - [Polish vascular prosthesis sealed by albumin]. AB - TRICOMED, Medical Articles has been conducting its research on textile vascular prostheses for over 35 years. In the seventies, a collagen coated graft was designed and fabricated which, however, after having been positively evaluated ceased to be used by clinics. In the eighties, double velour DALLONR prostheses was introduced which are now marketed by our company. The DALLONR graft has a low mass, developed surface area and moderate porosity. In the eighties, foreign manufacturers launched various types of coated grafts. Responding to that popular market trend we have resumed our early research on the preclotted prostheses and started studies on the use of albumin and chitosan as coating agents. The grafts impregnated with albumin have achieved satisfactory results of biological and experimental testing. These results are confirmed by current clinical examination. PMID- 1305971 TI - [Clinical and tomographic evaluation of polyester prosthesis of the anterior crucial ligament made by TRICOMED in Lodz]. AB - This study involves 38 patients in the age is 24-51 years with the III degree instability of the knee who underwent ACL replacement with PPT artificial ligament, beginning from 1986. For the majority the operation mentioned above was the second or even the third intervention after the previous ones, meniscectomy and suture repair included. In 6 patients, who underwent BJ plastic method, the return of the instability was observed. 24 patients were examined after an average follow up time of 34 months. 1 patient was operated on for the ligament replacement 4 years after the first operation, another one was operated on for synthetic arthritis one year after. Estimation of the results is based on clinical examination, subjective professional opinion and CT. 21 patients showed excellent results, which correspond with CT examination and confirm good quality of PPT ligament. PMID- 1305972 TI - [Methods of testing materials made by a knitting technique]. AB - The author describes the methods of testing biomaterials manufactured by TRICOMED, Medical Articles, in Lodz. Examination of raw materials, production control methods, quality control of semi-finished and finished products are discussed. PMID- 1305973 TI - Hepatitis A vaccines. PMID- 1305974 TI - The consequences of passive smoking: an overview. AB - Tobacco smoke contains a wide range of toxic vapors and particles that when inhaled are injurious to the smoker himself (active smoking) and to those around him (passive smoking). It is extremely difficult to define precisely the harmful effects of passive smoking on the individual's health because of the problems involved in quantifying the extent of exposure. A number of epidemiological studies indicate that exposure to passive smoking in public places is circumstantially but marginally linked to cardiovascular morbidity and mortality, as well as to benign and malignant pulmonary morbidity. There is an increased risk of cardiovascular and lung diseases among people living with spouses who smoke due to the exposure to tobacco smoke in the home. Passive smoking during pregnancy constitutes a health hazard for mother and fetus alike. Exposure to passive smoking during childhood may predispose the individual to benign and malignant pulmonary morbidity in both childhood and adulthood. For many people the worksite comprises the main exposure source. Many clinical conditions are further aggravated by exposure to a combination of tobacco smoke and industrial chemicals, mineral dust, or other carcinogens (asbestos, cadmium, radon daughters). Tobacco smoke exposure and the resultant morbidity can be reduced by regulations and legislation prohibiting smoking in public places and worksites. PMID- 1305976 TI - The 1991 measles epidemic in Israel. AB - INTRODUCTION AND METHODS. Prior to the institution of universal childhood vaccination against measles in Israel in 1967, large outbreaks occurred in epidemic cycles at intervals of 2-4 years. The mean annual incidence in the pre vaccination period, 1950-66, was 470/100,000 per year. With the institution of routine measles vaccination, incidence rates fell, and since 1970 measles incidence has averaged less than one-tenth the pre-vaccination incidence rate, although epidemics occurred in 1975, 1982, 1984-85, and 1991. In this report, based upon cases of measles reported to and investigated by the Ministry of Health, we present an analysis of the 1991 measles epidemic, the measures taken to contain it, and an overview of the prospects for measles control in Israel in the future. RESULTS AND CONCLUSIONS. The 1991 measles epidemic, 1036 reported cases (incidence: 20.0/100,000), began in the south of the country among underimmunized Beduin children and spread to the Jewish population in the south and then to the rest of the country. The highest incidence was in children aged 12-23 months, followed by children less than 12 months of age and children aged 2 4 years. In the main, cases occurred in persons never immunized in the past, but in 37% of cases vaccine failure seems to have occurred. Control measures included mass vaccination of children in the south and lowering the age for routine measles vaccination nationwide to 12 months. Despite very substantial gains towards measles control in Israel, elimination of the disease is not a realistic goal, mainly because the transmission potential of the disease is too high and vaccine coverage and efficacy are not high enough. Trends in measles incidence over the last four decades allow a cautious optimism that measles containment can be achieved. PMID- 1305977 TI - Personal determinants of health promoting behavior. AB - This paper describes the personal determinants in health promoting behavior, and, in particular, life style changes. A review is made of internal factors, including personality factors, health beliefs, and health attitudes. Environment factors are also taken into account. Suggestions for future research are proposed. PMID- 1305975 TI - Reduction in hepatitis A antibody prevalence among young adults in Israel. AB - BACKGROUND: Hepatitis A (HAV) is endemic in Israel. A number of developed countries have reported marked reductions in prevalence of antibodies. The objective of this study was to determine whether change in prior infection took place over a 7-year period and to investigate the sociodemographic characteristics of infection in Israel. METHODS: Recruitment into military service in Israel at the age of 18 is compulsory. Representative samples of male recruits were selected in 1977 and 1984. Antibodies to HAV were tested by solid phase radioimmunoassay in the 1977 sample and by an enzyme immunoassay in the 1984 sample. RESULTS: HAV antibody prevalence in 1977 was 69% (95% confidence interval (CI) 65% to 72%) versus 54% (95% CI 49% to 59%) in 1984 (p < 0.0001). The reduction was evident in all ethnic-origin groups comprising the Jewish population. In 1984 the prevalence was 28% for Jewish men of European origin, 60% for Asian origin, and 80% for the North African origin group. A statistically significant independent effect of education was evident. CONCLUSIONS: These findings point to a reduction in feco-oral transmission and hepatitis A virus infection in childhood in Israel, yet reveal considerable continuing ethnic and educational inequalities in prior exposure to infection. A potential for large outbreaks exists during transition from high to low endemicity, particularly in high-risk military populations. These populations are candidates for application of active hepatitis A vaccines now undergoing testing. PMID- 1305978 TI - Tuberculosis cases in the Negev 1978-1987: ethnicity, sex, and age. AB - BACKGROUND: The incidence of tuberculosis (TB) in Sub-Sahara Africa is considered to be one of the highest in the world. During the past decade thousands of Jewish refugees from Ethiopia were settled in the Negev and might constitute a potential reservoir of infection for the indigenous populations. This study provides some baseline information about TB in the Negev just prior to and after an Ethiopian immigration peak. METHODS: The files of every case of TB diagnosed during the decade 1978-1987 at Soroka Medical Center were reviewed and each diagnosis was validated by rigorous clinical and microbiological criteria. The age, gender, and ethnic background of each case were recorded, and approximate population denominators were estimated from Ministry of Health and Census data. Annual and decade incidence rates were then calculated for the different demographic categories. RESULTS: 279 cases of TB were verified. The main 10-year incidence rate per 10,000 Israeli Jews was 0.28; for the Negev Beduins it was 1.52; for the Ethiopian Jews, 91.9. In the Jewish population, cases among males (59) far exceeded those among females (7), but the reverse was observed, both among the Beduins (47 female and 31 male cases) and the Ethiopian immigrants (79 female and 56 male cases). In all three groups TB incidence increased with age, ranging from 0.03 per 10,000 for young non-Ethiopian Jews to a remarkable 623.8 per 10,000 for elderly Ethiopian Jews. CONCLUSIONS: The results of this study indicate the existence of a potentially large TB reservoir in the Negev. Health workers must be alerted to the importance of continued case finding, effective case management, and the control of infection transmission. The unique integration of the Negev Health Delivery System should help monitor intervention strategies. PMID- 1305979 TI - Regional differences in appropriateness of cholecystectomy in a prepaid health insurance system. AB - BACKGROUND: Previous studies have reported variation in the population-based use rate of diagnostic and therapeutic procedures. Cholecystectomy is one of the most common surgical procedures, and we conducted this study to assess whether in Israel the use of this procedure varied by region and whether differences in use can be related to differences in appropriateness of use. In Israel, there is a pre-paid health insurance system and all surgeons are salaried. METHODS: Age adjusted rates of cholecystectomy in four hospitals, each serving a defined population in Israel, were calculated. Two hundred and sixty-six potential clinical indications for performing cholecystectomy were rated as to their appropriateness by a panel of 9 expert physicians. A trained team abstracted the medical records of all patients who underwent the operation in the four Israeli hospitals in 1986 (n = 702) and recorded the clinical indication for the surgery. RESULTS: The population-based age-adjusted rates of cholecystectomy varied over threefold among the four hospitals. 29% of the cholecystectomies were performed for less than appropriate reasons, and this figure varied by hospital from 36% to 17% (p = 0.002). However, appropriateness did not vary systematically with the population-based use rate. CONCLUSION: Cholecystectomy was performed frequently for inappropriate or equivocal reasons, even in a country in which resources are limited, and physicians are salaried. Efforts to improve surgical decision making should be undertaken. PMID- 1305980 TI - Assessment of health risks from fallout radiocesium in a hunting and food gathering society. AB - Hunting and food-gathering societies are particularly vulnerable to the effects of fallout, since these people are often at the head of natural food chains which can bioaccumulate toxic substances. This paper describes a study on the effects of fallout radiocesium in caribou consumers of northern Canada. Portable whole body counting equipment was transported into five Arctic communities in 1989-90 and used to measure radiocesium body burdens in over 1100 people. The results were compared with a similar survey carried out in 1967-68. The mean body burden for adults in each community had decreased by a factor of 20 to 30 since the earlier survey. It was possible to derive an effective half time of about 4.5 years for the decrease of Cs-137 body burdens in the Arctic. The mean lifetime dose from the ingestion of radiocesium since 1967 amounted to not more than 12 mSv, with possibly an equal contribution from the period before 1967. The current radiation doses are much less than natural background and it is possible to reassure northern residents that caribou meat remains a safe and nutritious food source. PMID- 1305981 TI - [Oral problems and approach to dental care in case of diabetes mellitus]. AB - Diabetic patients often present oral symptoms and complaints at the moment of diagnosis of their disease. Recurrence of these symptoms is possible in periods of poor metabolic control. Long term complications of the disease are noticed at the level of the oral cavity. Dentists can contribute to early recognition of oral manifestations. A careful dental follow-up of these patients is essential in order to reduce the incidence and severity of long term oral complications (advanced periodontal disease, ...) This article reviews the general and oral implications of diabetes mellitus and discusses the results of a clinical study regarding the orodental condition and oral preventive behaviour of children with diabetes. Practical guidelines for the dental care of patients with diabetes are outlined. PMID- 1305982 TI - [Survey on HIV and the control of infection]. AB - During FDI World Dental Congress 1990, field specialists set up a scientific question form to obtain specific information about hygiene procedures in dental offices, knowledge about oral lesions in HIV infection and attitude against HIV infected patients. 540 Belgian dentists replied the question forms correctly. In general, there are no big differences between male and female. Younger dentists seem to be more hygiene minded than older colleagues. But more important is the discrepancy between the risk level and the use of specific hygiene procedures, and the knowledge about specific HIV associated oral pathology. PMID- 1305983 TI - [The antiseptic role of saliva]. AB - The oral flora is under the control of both immunity and non specific defense factors. The immunity factors are mostly represented by polymorphonuclears immunoglobulins Non specific defense factors include lysozyme lactoferrin high molecular weight proteins, such as mucins fibronectin and beta 2 microglobulin histidine rich proteins cystatins salivary amylases salivary peroxidase system. PMID- 1305984 TI - ["Safe for Teeth" confectionery and the International Sympadent Federation]. AB - Preventive cariology has primarily focused on the protection of teeth with fluorides and on oral hygiene. Another important preventive approach, namely diet modification reducing the frequency of consumption of acid-producing carbohydrates has not yet gained enough attention. It can very well be implemented by making available a wide variety of non- or hypo-acidogenic snacks. This paper presents a model system, the Swiss Sympadent Association, initiated and currently used in Switzerland for developing, testing, labelling and promoting "tooth-friendly" foods that do not give rise to intraplaque acid production. Based on the success of the Association in Switzerland, an international extension of this model is well on its way. PMID- 1305985 TI - [Chewing gum and dental health. Literature review]. AB - Clinical studies have demonstrated the caries promoting effects of sugar based gum when compared with non sugar chewing controls. Sucrose gum has been shown to stimulate plaque growth and increase its adhesivity. Acid produced in plaque and mixed saliva whilst chewing sugar gum is counteracted by the buffering action of mastication induced saliva. However the vast majority of studies measuring plaque pH has demonstrated acidification of plaque during use of sugar gum into the decalcifying zone (pH < or = 5.5), or after the gum is taken out. Sugar gum causes a more pronounced fall in plaque pH in individuals with an increased caries risk compared to the pH drop in more caries resistant individuals. Sorbitol, by itself or in combination with mannitol is slowly converted to acids by the plaque microorganisms. Chewing gums sweetened with these sugar alcohols do not cause a critical acidification of the plaque and appear not to promote caries in the clinical trial. Twelve weeks use of sorbitol chewing gum has been shown to induce a plaque more adapted to form acids from this sugar alcohol. This adaptation has been shown to persist for up to twelve weeks after cessation of the use of the sorbitol gum. Xylitol has generally been considered non-cariogenic because of its non-fermentability by most important plaque microorganisms. Plaque pH and pH of mixed saliva is increased during and following the use of xylitol based chewing gum. Prolonged use of xylitol or xylitol containing chewing gum reduces Streptococcus mutans counts in plaque and saliva, at the same time fostering remineralization of early caries lesions. Regular use of xylitol reduces the acidogenic potential of the plaque as well as its adhesiveness, at the same time increasing its mineral content. No adaptive changes in plaque metabolism resulting in the fermentation of xylitol have been reported, not even after long term, intense use. Xylitol chewing gum therefore is eminently suited to be used as part of a caries preventive regimen notably for high caries risk patients and those suffering from xerostomia. Adding mineral salts to sugar based chewing gum has been demonstrated to significantly inhibit caries development. Possible additional caries preventive benefits of mineral compounds added to sugar-free chewing gum have, so far not been reported. Sugar-free chewing gum has been shown to be an excellent vehicle for Fluoride. The plaque-growth retarding properties of Chlorhexidine-containing chewing gum have been shown to equal that of a Chlorhexidine mouthwash. Ureum added to a sugar-free chewing gum helps to neutralize plaque acids by liberating basic ammonia. PMID- 1305986 TI - [Prevention of alveolar bone loss]. AB - This article describes the bone resorption and remodeling of the edentulous jaw, starting right after extraction of teeth. This resorption is a physiological process, but can be influenced by wearing dentures. Load on the mucosa and disturbed blood circulation of the mucosa caused by the denture gives an additional bone resorption. The prevention of bone resorption can be executed in saving teeth or roots as long as possible. But when the jaw is already edentulous it is necessary to create an optimal function and load-dividing of the denture and regular controls are indicated. From time to time the denture has to be rebased or relined due to the changes in contour of the jaw. Also a daily massage of the mucosa after cleaning the denture is advisable to restore a normal blood circulation. PMID- 1305987 TI - [Lack of healing following adequate endodontic treatment]. AB - When an endodontic treatment is to be redone, generally the X-ray reveals some form of poor or inadequate filling. Most endodontic cases fail because of inadequate endodontic treatment (cleaning, shaping, filling). However, sometimes good clinical treatment isn't followed by healing! This article sums up the possible reasons to consider. In order to improve the success rate of the endodontic treatments, practical hints are given regarding the non-surgical as well as the surgical (re)treatments. PMID- 1305988 TI - [Access to root canals]. AB - Both for the future of the residual dental crown and in order to work efficiently in the canals, preparation of the pulp chamber should be regarded as more than a mere stage. Although it is only a transitory stage, it is essential that the pulp chamber should be clean and well cleared without wasting healthy dental tissue. A good access, without excess, will increase the chances of success. PMID- 1305989 TI - [Determination of tooth length in endodontics]. AB - Determination of the exact tooth length and subsequent working length remains a corner stone of proper endodontic treatment. Up to now, no system has proven to provide the exact location of the apical constriction under all circumstances. Several possibilities of determining tooth length are discussed. Factors influencing the outcome of the different techniques are described. A simple and rather accurate way for calculating tooth length on X-rays is elaborated. Apparently, electronic devices are becoming increasingly accurate, and may become a challenge for the radiographic tooth length determination. Actually, dentists have most of all to rely on X-rays for tooth length determination. PMID- 1305990 TI - [Electronic apex localizers: useful instruments or inconvenient gadgets?]. AB - Apex locators offer definite advantages for certain patients over conventional radiographic methods of root canal length measurement. Current instruments do not appear to differ significantly in accuracy. The choice of locator has to be made therefore on cost and convenience in use. The current best buys seem to be the Evident RCM and NeoSono MC. Both offer good value for money, the Evident is the less expensive but lacks some of the additional features of the NeoSono. The decision to buy an apex locator should only be made after a period of testing in clinical practice. PMID- 1305991 TI - [Rational basis for resumption of treatment in endodontics. Should it be "down to the root" in order to be satisfied in endodontics?]. AB - Any endodontic treatment showing a symptomatology should be retreated or corrected. Should we start the asymptomatic treatments over again when the x-ray does not show a filling that is complete, hermetically sealed, biological and under control? When the case arises, the decision to resume the treatment will depend on the state of the crown restoration: should it be redone for any reason? 1. When the crown filling does not need to be removed and redone, watchful waiting is recommended. 2. When the crown filling is deficient, and has to be redone, it would be advisable to resume or try to resume all the canal treatments that are not hermetically sealed, when an opening to the canal has to be worked out. Several experiences show that the rate of success of endodontic treatments that have been resumed is lower than that of endodontic treatments that have been carried out for the first time. Should radiographically inadequate but asymptomatic endodontic treatments not be resumed, it would result in problems only in a very small number of cases, as long as the state of intracanal balance is not broken. PMID- 1305992 TI - [Medications for endodontic use]. AB - Medication can never disinfect a badly shaped canal and successful treatment will depend on the endocanal preparation. Despite the indisputable antibacterial efficacy of Rockles 4 in vitro, use of this medicament should be banned because of its toxicity, its mutagenic and antigenic action and its long-term inefficacy in vivo. The same goes for all other antiseptics, anti-inflammatory agents and antibiotics mentioned, that should be discarded because of their harmful effects on patients or their inefficacy on endodontic flora. Our endodontic medicine cabinet should only contain the following products: irrigation agent: NaOCl 2.5% medication in 2 sessions: calcium hydroxide prescription or 'Reogan rapide'. PMID- 1305993 TI - [Lasers in endodontics]. AB - Laser technology has been developed rapidly in the last decade. New lasers with a wide range of characteristics are available now which are being used in various branches of dentistry. The application of these new technologies in endodontics has always been challenging. Today more experience and knowledge in applying lasers in endodontics is available. PMID- 1305994 TI - Long-term effects of isotretinoin in the treatment of severe nodulocystic acne. AB - One hundred and sixteen patients with severe nodulocystic acne were treated with 0.75 mg/kg isotretinoin daily for 6 months. One hundred and seven (92%) were completely healed or markedly improved at the end of treatment compared to 94 (81%) 42 months later. There was no significant difference in the clinical response between male and female patients. Seven of the 40 female patients gave birth to 7 fully developed and healthy children 39 months after discontinuation of therapy. Cheilitis (84%) and dry skin (54%) were the most common side effects, the severity of the side effects being dose-related. Increased serum triglyceride values following treatment were found in 31 (27%) of the patients. A better life quality was experienced by 99 (85%) patients after isotretinoin therapy. PMID- 1305995 TI - Twenty-four-hour intragastric pH-metry: evidence of nightly gastric alkalinization in subjects with and without active duodenal ulcer. AB - Continuous 24-hour gastric pH monitoring was performed in 68 subjects to evaluate the spontaneous nightly alkalinization phenomenon (SNA). Two groups of patients were compared: the first (group A) was composed of 27 subjects with active duodenal ulcer disease; group B included 12 healthy volunteers and 29 patients with gastroesophageal reflux. Patients with duodenal disease had an alkalinization of 196.2 +/- 97.9 seconds in duration, while healthy subjects and even gastroesophageal refluxers exhibit a SNA lasting 5269 +/- 748.3 seconds (t = 6.72; p < 0.001). The absence of SNA was used as a predictive test of duodenal ulcer disease and its discriminating ability was evaluated. The evidence of this phenomenon was able to exclude the disease in 90% of group B subjects (negative predictive value) while its absence suggested correctly the presence of duodenal disease in 82% of patients (positive predictive value). The lack of SNA in duodenal ulcer patients is so frequent that its absence might be a diagnostic sign of the peptic disease. PMID- 1305996 TI - Intravenous propafenone for suppression of symptomatic atrial fibrillation and atrial flutter in a first aid hospital. AB - The efficacy and safety of propafenone (PPF) were prospectively evaluated in 20 patients (13 men and 7 women, age 39 +/- 14 years) with atrial arrhythmias (AA) (atrial fibrillation: n = 13; atrial flutter: n = 7). All patients had arrhythmias from 109 +/- 63 minutes, (iT) without clinical evidence of heart failure. Intravenous PPF was given as a 1 mg/kg bolus over 5 minutes, with a therapeutical possibility of a second bolus (1 mg/kg) after 10 minutes if sinus rhythm was not restored. The conversion time (cT) was 6.4 +/- 2.2 minutes (range 3 to 18 minutes). In 19 patients (95%) sinus rhythm was restored and no serious adverse and proarrhythmic effects were noted in each patient. We conclude that 1) PPF is effective and acted significantly faster in controlling AA; 2) PPF appears to be well tolerated and relative safe with a low incidence of adverse and proarrhythmic effects in patients in a first aid station. PMID- 1305997 TI - Food allergy, atopic dermatitis and superficialism in medicine. AB - Although the essential immunology underlying atopic diseases is now being clarified, there are still few accountable diagnostic tests. Therefore the recognition and treatment of these diseases continues to be based mainly on clinical skill and, in particular, on the taking of a careful history. This means that the observer bias can be a significant factor, and so whether or not the diagnosis is made may dependent on a clinician's preconceptions. Furthermore, the general interest in the subjects has tended to divided the medical consensus between believers and nonbelievers. In infancy, food allergy has protean manifestations and is provoked by many different food allergens. In addition to the lack of really useful diagnostic tests, there is the difficulty of easily and reliably conducting double-blind challenges in general pediatric practice. Thus it is crucial that a scientific, and critical, approach is adopted and that doctors attentively record the case history and observe the response to elimination diets and challenges. True science has nothing to do with superficialism. PMID- 1305998 TI - [Changes in lymphocyte subsets in chronic inflammatory diseases and neoplasms in the elderly. I. Multivariate analysis of variance and factoral analysis]. AB - The variations of lymphocyte subsets have been studied both in neoplastic and chronic inflammatory elderly patients compared to a control group. The interpretation of the Multivariate Analysis of Variance (MANOVA) and of the Factorial Analysis has demonstrated the opposite role of TCD4 subset, mainly involved in the inflammatory process, and of TCD8 subset in regard of the neoplastic ones. We report the slight and yet significant increase of NK related to age. Independently from the disease pattern, factorial analysis permitted a comparison between the variations of lymphocyte subsets and the different grades of immunoresponse. PMID- 1305999 TI - [Surgical treatment of inguinal hernias with local anesthesia]. AB - Fifty-nine cases of inguinal hernia repair with local anesthesia are shown. The authors stress the advantages of this safe technique permitting an immediate postoperative ambulation and an early discharge of patients, thus reducing complications related a long term bed-stay. PMID- 1306000 TI - [Pulmonary hamartoma in geriatric surgery]. AB - The pulmonary hamartoma is a kind of disease frequently shown in elderly. The diagnosis is often difficult and fine needle aspiration (FNA) can be used for histological features. CT scan can be also a such useful technique in differential diagnosis. A case is presented and its problems are discussed. PMID- 1306001 TI - [Tracheostomy: indications, techniques, and complications]. AB - The authors report their experience relative to 46 tracheostomies performed over a 10-year period. In 6 cases the indication for a tracheostomy was a post traumatic respiratory failure; in 20 cases a chronic respiratory insufficiency, in 6 cases a malignant neoplasm of the larynx; in 10 cases a postoperative respiratory insufficiency; in 4 cases for tongue and/or neck wounds. The authors stress the importance of a correct indication, the use of large volume-low pressure cuffs and an appropriate surgical technique to prevent complication of tracheostomy. PMID- 1306002 TI - [Gingival hyperplasia induced by cyclosporin A]. AB - Cyclosporine-A (Cy-A) selectively inhibits T cell function with minimal effect on humoral immunity. It is used specially in transplantation patients and in some cases, like other drugs, it causes gingival hyperplasia. In this article, after a review of the most recent pathogenetic hypothesis, the authors present their experience based on 10 cases of gingival hyperplasia in kidney transplantation patients in treatment with Cy-A. PMID- 1306003 TI - [Clinical-therapeutic considerations in pertussis]. AB - One-hundred and seventy-one cases of pertussis were observed at the Institute of Infections Diseases and at the 2nd Division of Infectious Diseases of the Policlinico Umberto I in Rome from January 1, 1987 to June 30, 1991. All subjects were treated according to a therapeutic protocol consisting of macrolides (erythromycin or myocamicin) at doses of 40-50 mg/die, betamethasone 0.1 mg/kg/die, specific immunoglobulin G at doses of 0.5 ml/kg repeated after 24 hours (new born babies and babies still unweaned) and oxygen therapy during the paroxystic fits. In 20 patients who were over the first year of life and who had serious asphyxiated fits, bronchodilators (trimetochinol or salbutamol) were added to the previous therapeutic scheme. Our data show both efficacy of therapeutic protocol and importance of early starting the treatment to shorten the length of disease, the strength of asphyxiated fits, and the risk of contagion. PMID- 1306004 TI - [Effects of a heparin-heparinoid combination on esthesiologic and trophic changes in deep periarticular tissues in gonarthritis]. AB - We evaluated the efficacy of heparin-glucuronylglucosaminoglycane association topically used on periarticular deep tissues (subcutaneous and muscle), in 20 females divided into two homogeneous groups of 10 each, affected by painful osteoarthritis of the knee. Electrically stimulated subcutaneous and muscular pain thresholds have been assessed; ultrasound scan of subcutaneous tissue overlying articular rima and vastus medialis muscle, and ultrasound scan of vastus medialis muscle thickness have been also examined. The measurements have been done (at the beginning of the experiment) in basal conditions and respectively after one, two, and three weeks treatment with the drug or placebo administered in a double blind fashion. Subcutaneous and muscular pain thresholds have shown an important rise right from the first week of treatment; subcutaneous tissue thickness was significantly decreased after two weeks treatment and in the same period a significant increase of vastus medialis muscle was registered. No such variations have been shown after placebo treatment. The possible mechanisms of such effects have been assessed in a peripheral control action of inflammation, with decrease of nociceptive message and consequent limitation of dystrophic reflex phenomena. PMID- 1306005 TI - [Morphologic changes in cardiac muscle in white rats in various models of hypoxia]. AB - The authors have explored the effect of intermittent hypoxia in the cell membrane and histochemical changes in the cardiac muscle cells of the white rat. Every day the animals were exposed to experimental conditions characteristic of 7.000 m of high above sea level (first experimental group) and every odd day (second experimental group). Animals of the experimental groups were sacrificed immediately (first subgroup), 24 hours later (second subgroup) and 7 days after the final exposition (third subgroup). The hypoxical stress elicited the vacuolation of the cardiac muscle fibres of the subendocardiac layer of miocard which persisted, and did not reduce its number, intensity and extensity in the first experimental group, although it reduced its intensity and vacuoles size in the second experimental group, while in fuxinorrhagia which has been presented focally the intensity has been reduced in all the three subgroups of the first experimental group of animals. In preparations of animals from the second group, sacrificed 24 hours after the experiment intensity and extensity fell to the half number of those animals, and completely disappeared in those sacrificed 7 days after the final exposure. Glycogen pools, as well as the activity of sucinat dehydrogenase were preserved in both experimental groups. It could be concluded that apart from hypoxia model, oxygen deficit, too, elicites ischemical changes in the sense of vacuolation of muscle tissue which does not disappear or its disappearance has been much slower than in positive fuxinorrhagia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306006 TI - [Occurrence of triplet births]. AB - The authors studied all cases of triplets who were born at the Department of Gynaecology and Obstetrics of University Clinical Centre in Belgrade, over a twenty-year period (1970-1989). Thirty sets of triplets were born in this period. This means that one set of triplets was born per 5845 births. Preterm deliveries occurred in 19 cases. Liveborn children had lower Apgar score. Common birthweight was slightly below 1800 grams. In more than one half of the foetuses malpresentation was found. More than one fourth of sets were delivered by Cesarean section. Total foetal loss reached 23.33% and purified perinatal mortality rate reached 11.11%. The triplet diagnosis on time is important because of the necessary prevention measures and appropriate therapy. PMID- 1306007 TI - [Clear cell sarcoma of the kidney in children]. AB - Clear cell sarcoma of the kidney (CCSK) is a distinct, highly malignant renal tumour of childhood which was diagnosed in 5 (3.9%) of 133 primary renal tumours in children under 15 years of age in the period from 1976 to 1990. The clinical and pathological features of these patients are presented. The most common clinical features were abdominal mass and haematuria. The male to female ratio was 1: 1.5 and there was predilection for the left side (4:1). The age of patients varied from 5 months to 4 years (average age 23 months). In four children the tumour was in Stage I, and in one child in Stage II. Three tumours showed classical microscopic pattern of CCSK. The treatment for all patients consisted of preoperative chemotherapy, radical surgery and additional aggressive chemotherapy. Four patients developed metastases: three of them to bones and one to the liver. Three patients died of the tumour, one is alive but with the tumour (3 years follow-up), and one child is alive and without any evidence of disease (3-years follow-up). Although relatively uncommon, these tumours are responsible for 50% of all children's deaths from renal tumours and, so, their precise classification is essential for proper treatment. PMID- 1306008 TI - [Efficacy of therapy, recurrence of seizures and respiratory complications in the treatment of status epilepticus by intravenous administration of diazepam or midazolam]. AB - During a nine-month period we have treated 46 patients with status epilepticus with intravenous application of diazepam or midazolam. The initial doze od diazepam was 10 mg (rate: 2-5 mg/min) and of midazolam 15 mg (rate: 5 mg/min). Diazepam was effective in 26 and ineffective in 15 patients. Midazolam stopped status in 4 out of 7 patients. Both drugs were more effective when they were administered at the beginning of status. After the initial termination of status and recovering of consciousness, seizures returned in 10 patients (22%). In the group treated with diazepam, 4 patients had sudden apnea and 6 respiratory depression (totally 10 out of 41). In the group treated with midazolam, 3 had apnea and 2 respiratory depression (totally 5 out of 7). All patients with apnea or respiratory depression received higher doses of both drugs at the higher rates than the others. We conclude that the efficacy of the therapy is moderate while the frequency of serious complications is high. In status epilepticus, where the life of patient is in danger, drugs with such activity are of limited value. PMID- 1306009 TI - [Personal experience in the diagnosis and therapy of pulmonary thromboembolism]. AB - The analysis of both clinical findings and diagnostic procedures results were performed in 26 patients with thromboembolic pulmonary disease in order to determine the incidence of signs indicating pulmonary thromboembolism. Sudden dyspnea, hemoptysis and chest pains are the most common symptoms of the disease. These symptoms associated with radiographically confirmed pulmonary infiltrations with the elevation of hemidiaphragm and pleural effusion, particularly if they are bilateral, are the main clues for the diagnosis of pulmonary embolism. Perfusion defect on the pulmonary scintigraphy makes this diagnosis almost certain. Hypoxemia and hypocapnia and respiratory alkalosis are frequent findings in thromboembolic pulmonary disease, as well. Fever, increases RBC sedimentation rate and leukocytosis are present in a great deal of patients. In addition, the presence of risk factors related to the development of thrombosis of the lower limbs deep veins, and particularly those related to the long term immobilization as well as diagnostically confirmed venous thrombus are basic guidelines for the diagnostic of pulmonary thromboembolism. PMID- 1306010 TI - [Subclinical disorders of left ventricular function in diabetics detected by echocardiography]. AB - In diabetic patients, without coronary heart disease and hypertension, left ventricular filing dysfunction exist, that is registered by echocardiography. It is manifested as greater peak flow velocity during atrial systole and as shorter time from the aortic second heart sound to the peak of the early diastolic flow velocity curve. The diastolic dysfunction indicates increased left ventricular stiffness and may be the first maker of diabetic cardiomyopathy. PMID- 1306011 TI - [Microscopic diagnosis of verrucous carcinoma]. AB - Twelve cases of verrucous carcinoma of the orofacial region were reviewed for their clinical and pathological characteristics. Verrucous carcinoma made 3.5% of all primary epidermoid carcinoma observed during the period of investigation. The tumour occurred chiefly in older patients (from 25 to 81 years, mean age 57.5) and more often in males than in females (9 males: 3 females). The most common site of occurrence was the vermilion surface of the lower lip (seven cases). Macroscopic appearance of lesions was reported as exophytic, warty, and white. Microscopically, the thickened epithelium was well differentiated and stratification was preserved. Rete pegs of carcinoma were broad and blunt; they also appeared to "puch" into underlying tissues. Basement membrane appeared to be intact. Cells of tumours were displayed, and histologic features of the spectrum were generally associated with viral modification. The prognosis in verrucous carcinoma is very good, because of the absence of metastases. Radiotherapy should not be used, since not only local recurrence is common, but also anaplastic changes may occur with corresponding aggressive behaviour and metastasis. PMID- 1306012 TI - [Mycobacteriosis]. AB - Classification of atypical mycobacteria, problems related to their identification, epidemiological, clinical, radiological and pathohistological presentation of mycobacteriosis are given. Up-to-date alternatives for treatment of these patients are also given. Finally, three cases treated at the VII Clinical Ward of the Institute of Pulmonary Diseases and TBC in the course of 1990 are presented. In two of them Mycobacterium avium was isolated. In all three cases the same strains were isolated and identified repeatedly. PMID- 1306013 TI - [Radiotherapy of metastatic brain tumors]. AB - On the basis of data from literature, the authors present the role of radiotherapy in the treatment of brain metastases. This role has been considered as a sole treatment or as a combined treatment, especially with surgery. New techniques of radiotherapy which could enable better results in the treatment of brain metastases in the future, are presented. PMID- 1306014 TI - [McArdle's disease]. AB - Glycogenosis type V (McArdle disease) is a serious metabolic disorder with an exercise intolerance, myalgia, early fatigue and stiffness of exercising muscles, relieved++ by rest. The authors present a case report of patient with McArdle's disease, and diagnostic procedures which can be used in different diagnostic of metabolic myopathies, especially between myoadenylate deaminase deficiency and different types of gly(geno)lytic myopathies. The importance of "ischemic forearm test" and muscle biopsy is emphasized. PMID- 1306015 TI - [Clinical significance of the negative T wave and changes in the ST segment in the electrocardiogram of air force pilots]. AB - More and more investigators, consider that nonspecific ECG changes are significant in prognosis of appearance of ischemic heart disease. It is seldom, appearance of disorder in ECG records in so high selected population, as pilots in Air Force. Around 4% of flyers present ECG record which could be of clinical importance. PMID- 1306016 TI - [Ophthalmologic manifestations in patients with ichthyosis]. AB - Different manifestations on some ocular and adnexal structures may accompany ichthyosis. Some ophthalmological manifestations in the clinical course of ichthyosis may endanger the eye and even lead to the sight loss. The paper reports a case of a patient with congenital ichthyosiform erythrodermia and ophthalmological manifestations on the lids and cornea. In addition to ichthyosis of the lid skin, squamous blepharitis and cicatricial ectropium of the lower lids were also present, while signs of exposure keratitis on the right eye and corneal leucostaphyloma on the left eye were also noted. Presence of lagophthalmos and permanent exposure of both eyeballs led to deterioration of the condition which may result in the sight loss on the right eye, as well. Therefore, contracture release of both lower lids was performed followed by full-thickness skin graft. Surgical procedure and the postoperative course were uneventful. The operation successfully corrected position of the lower lids and enabled formation and reestablishment of the precorneal tears film which led to improvement of the condition of the cornea. The effect has been maintained for six postoperative years now. PMID- 1306017 TI - [Diagnostic value of the NBT-PABA test in the functional evaluation of the exocrine pancreas]. AB - N benzoyl-L-tyrosil PABA was orally administered to 13 controls and 35 patients with pancreatic disease: 7 with chronic exocrine pancreatic disease, 7 patients after an attack of acute pancreatitis, 3 with carcinoma of the pancreas, 8 with biliary tract disease and 10 with diabetes. The amount of PABA excreted serves as parameter exocrine pancreatic function. PABA excretion in patients with chronic pancreatitis (p < 0.01) and diabetes (p < 0.05) was significantly less then in controls. The present data justify further investigation of this procedure as a possible new oral test of exocrine pancreatic function. PMID- 1306018 TI - [Dietetic-hygienic measures in the control of arterial hypertension in obese females]. AB - Since the evidence to data suggest that some obese person respond well to non pharmacological measures, the aim of this study was to examine the extent of body weight reduction necessary to reduce blood pressure to normal values. A group of 250 obese women with hypertension (blood pressure measurements over 160/95) and an overweight of at least 20 per cent excess of ideal weight was included in the study. The patients were advised to take well balanced low-calorie (about 1000 kcal/day) diet containing 66 g proteins, 140 g carbohydrates, 13 g fat and 0.5 g salt. They were advised to increase daily physical activities. Low-calorie diets were used to decrease body weight in groups of patients with changed of unchanged antihypertensive drug therapy, also. Decrease in body weight resulted in significant decrease in blood pressure; over two-thirds of complaint patients achieve normal blood pressure with a loss of only 5-10 per cent of their weight excess even if at this point they were still overweight. In the group receiving no drug therapy 78 per cent reached normal blood pressure, 76 per cent in the patients whose antihypertensive treatment had to be modified during the study and 63 per cent in the group receiving unchanged drug therapy. It was concluded that weight reduction program (diet and physical activity) can be a possible approach to treat hypertension without drugs and patients can attain normotension long before achieving the ideal weight. PMID- 1306019 TI - [Levels of immunoreactive atrial natriuretic peptide in the blood of children on hemodialysis therapy]. AB - Expansion of extracellular fluid volume,--increasing right atrial pressure,- appears to be a major stimulus for the rise in plasma atrial natriuretic peptide (ANP). End-stage renal disease (ESRD) is associated with significant changes of several hormone systems. Recent studies have shown that plasma ANP concentration is significantly increased in patients with ESRD and that the concentration of the hormone declines following haemodialysis (HD). In patients with ESRD treated by HD "dry weight" for each individual patient is the body weight at which the patients has normal hydration status. The aim of the present study was to determine changes of plasma concentrations of ANP during haemodialysis. We also attempted to check whether the baseline levels of ANP were related to weight loss during dialysis. Eleven children (7 females, 4 males) participated in the study. The patients age related from 8 to 20 years. Plasma concentrations were markedly elevated (p < 0.01) before haemodialysis (251 ae 119) pg/ml) in comparison with control values (61 ae 23 pg/ml), but remained above normal range in all except 4 cases. During HD body weight was reduced in all but one patient. This patient was infused isotonic fluid during HD and did not show weight loss. The four patients who had normal plasma ANP levels at the end of treatment appeared to be in better overall condition than the other patients. In summary, plasma ANP measurements may be of value in establishing the volume status in patients with ESRD. Plasma ANP levels after HD may help to adjust the right dry body weight for each patient. PMID- 1306020 TI - [The effect of recombinant human erythropoietin on erythrocyte lines in patients with anemia and chronic renal insufficiency]. AB - Blood counts, bone marrow cytology and iron status in 13 patients with severe renal anemia assessed prior to and after recombinant human erythropoietin treatment. The mean increase of PCV after 8 weeks of treatment was 50%. Simultaneously, we observed a fourfold increase of the reticulocyte count. This increment correlated with a twofold increase of the percentage of bone marrow erythroblasts. We also observed an increment of the relative number of erythropoietin-dependent early erythroblasts. The tager PCV of 0.30 was achieved in 4 of 5 predialysis patients, but was not achieved in 8 hemodialysis patients because they had an "absolute" bone marrow erythroblastopenia. In conclusion, conventional hematologic examination revealed that application of recombinant human erythropoietin leads to improvement of erythrocytopoiesis in different stages of chronic renal failure. PMID- 1306021 TI - [Correlation of sonographic and patho-anatomic findings in myomatous changes in the uterus]. AB - In spite of the fact that ultrasound is an accessory diagnostic measure in gynaecology, added to clinical examination, it can help in a more accurate diagnosis and better preparation for surgery. The comparison of data obtained by ultrasonic and macroscopic measurements of uterine leiomyoma in 130 patients did not reveal a statistically significant difference between the two methods. The mean size of all measured leiomyomas was 61.47 mm in longitudinal diameter, 53.00 mm in anteroposterior and 53.95 mm in transversal. Measured by ultrasound the mean dimensions of the same diameters were 62.29 mm, 56.91 mm and 55.11 mm respectively. Differences in the mean values of all measured diameters obtained in some cases can be explained by subjective elements in the use of ultrasound, the examiners experience and postoperative reduction of the removed organ volume, as well as by technical factors which may influence the ultrasonic image. Thus, the accuracy of ultrasonic measurement completes the knowledge about the size of the pelvic mass; it is helpful in preparation for surgery, and decreases the possibility of unexpected situations during the surgery. PMID- 1306022 TI - [Primary gastrointestinal non-Hodgkin's lymphomas]. AB - A retrospective study of seventeen patients with primary gastrointestinal Non Hodgkin's Lymphomas (GI-NHL) is presented. The sites of location were: the stomach (12 patients), the small intestine (2 patients), the ileocecal region (1 patient), the colon (1 patient), the stomach and the small intestine (1 patient). The mean age of the patients was 45.5 years. Histopathologic features were classified in accordance with the Working Formulation. Radical surgical resection of the tumour was performed in 14 patients. Laparotomy and biopsy were performed in one patient. The cases were grouped on the basis of: physical examination, surgical report and additional studies (bone marrow biopsy, lymphangiogram, radiograms..). Dawson et al have cited four criteria necessary for lymphoma of GI tract to be primary considered: 1) no enlargement of peripheral or mediastinal lymph nodes; 2) normal white blood cell count; 3) predominance of alimentary tract lesions with only regional lymph node involvement; and 4) no involvement of liver and spleen. After the surgical resection a combined chemotherapy was used in 15 patients. The operation was followed by irradiation in one case. Chemotherapy was refused by one patient. The better outlook in primary gastric lymphomas than in intestinal lymphomas was noted. The majority of investigators reported that gastric lymphoma was associated with better prognosis than intestinal lymphoma, one possible explanation being that gastric lymphoma was more likely to be diagnosed at an earlier stage. PMID- 1306024 TI - [A congenital lung cyst in a child with clinical manifestations after a 7-year latent period]. AB - Congenital cysts of the lung originate from embryological malformation of the lung bud and usually produce clinical signs in the first months of life by expansion, causing respiratory distress, or by infection through its bronchial communication. We report a rare case of solitary congenital lung cyst in the middle lobe which was diagnosed in the 3rd month of life and remained silent until the 7th year when tension pneumothorax developed from rupture of the rapidly expanding cyst. An urgent lobectomy of the involved lobe was performed. This rare case supports the attitude that every congenital cyst of the lung should be excised as soon as the correct diagnosis is established in order to prevent serious complications. PMID- 1306023 TI - [The hardness of drinking water and cardiovascular diseases]. AB - The paper deals with the results of the investigations so far, which have pointed out an inverse correlation between drinking-water hardness and morbidity and mortality rates of cardiovascular diseases. Among the water hardness elements special attention has been given to magnesium, as its deficiency in organism is likely to present an important risk factor for cardiovascular disorders. The options of preventive measures in this field are discussed-adding of magnesium to soft drinking-waters, salt enriched with magnesium, consumption of natural mineral waters, or Mg supplements. PMID- 1306025 TI - [Extramedullary blast transformation in chronic granulocytic leukemia]. AB - A patient with Ph1(Philadelphia chromosome) positive chronic granulocytic leukemia and extramedullary blast transformation (crisis) in lymph nodes of neck and axillae which appeared after 4-year of treatment with busulfan is presented. Biopsy of lymph node and histopathological examination showed lymphoblastic infiltration. The patient was treated with radiotherapy and chemotherapy with protocol COP. He survived 7 months and expired due to renal insufficiency. PMID- 1306026 TI - [Wilson's disease and pregnancy]. AB - Wilson's disease is rare autosomal-recessive disorder originated on the basis of metabolic copper over-storage. This is the case report of patient aged 28, who suffers Wilson's disease during last ten years. She has been treated by penicillamine unregularly from the beginning of her disease. She reported three spontaneous abortions in her previous history. She was treated by penicillamin and bedoxin in current pregnancy. Vaginal delivery was completed using oxytocin stimulation. Newborn was male, alive, with body weight of 2900 grams. Apgar score was 8. During puerperal period normal uterine involution was estimated, but lactation was ceased. PMID- 1306027 TI - [House dust as a cause of disease]. AB - Allergens due to mites, especially to the most common species Dermatophagoides pteronyssinus and D. farinae has been recognized as a major health problem. The role of mites of the family Pyroglyphides as the single most important source of house dust allergens was established in 1964. There has been steady progress in understanding of the way in which allergen from mites can contribute to asthma, rhinitis and atopic dermatitis. Increased knowledge of the biology of mites has also allowed the development of improved protocols for reducing the quantities of mite allergens in house and has resulted in clear evidence that such measures can help patients. PMID- 1306028 TI - [Doctor Laza K. Lazarevic and the history of Serbian gerontology]. PMID- 1306029 TI - Behavioral effects of stem-leaves extract from panax ginseng C.A. Meyer. AB - The behavioral effects of extracts from ginseng stem and leaves (GL), standardized with respect to the total saponines, and from ginseng roots (G115), standardized with respect to the content of ginsenosides were examined in experiments on rats with undisturbed memory and in rats with experimentally impaired memory (electroconvulsive shock) using the methods for active avoidance (shuttle-box) and passive avoidance (step-down, step-through), the water-maze method and the method for studying exploratory behavior. On multiple administration G115 exerted favorable effects on learning and memory and on the higher nervous activity as a whole. These effects greatly varied with the dose and administration schedules, with the rat strain, with the rat's ability to perform adequately in any particular learning task, and with the behavioral method. The extract from the overground part of ginseng (GL) had, in the majority of cases, an effect weaker than that of G115 or was without effect at all. Based on previous and present results, we discuss the role of the changes in brain biogenic monoamines induced by the extracts for their mechanism of action. PMID- 1306030 TI - Effects of diazepam on somatosensory evoked potentials in rats at two different periods of day. AB - The effects of diazepam (5 mg/kg i.v.) on somatosensory evoked potentials (SEPs) were investigated in rats in acute experiments. Generally an increase of the peak latencies and a reduction of the amplitudes were observed immediately after diazepam (DZP) administration. An account was given of the differences in the DZP effect on SEP when the drug was applied at two different periods of day. The late cortical components were affected in both day and night, whereas the early and intermediate potentials were influenced by DZP only during the light period of day. The late N17 proved to be more sensitive to DZP in the night recordings. Our results suggest that the DZP effect on SEP in daylight conditions is more pronounced than that at night. The possible mechanisms responsible for this difference were discussed. PMID- 1306031 TI - Dilute local anesthetics in epidural analgesic solutions. PMID- 1306032 TI - Decreased circulation time in the upper limb reduces the lag time of the finger pulse oximeter response. AB - To observe the influence of circulatory changes on the lag time of the pulse oximeter response, eight healthy patients scheduled for hand surgery were studied. After breath holding, the patients took a breath of oxygen and the time to an increase in SpO2 was measured before and after axillary brachial plexus block. It was found that the lag time with finger probe decreased from 28.6 +/- 7.1 sec to 15.8 +/- 1.1 sec (mean +/- SD) following brachial block (P less than 0.01). There was no change in arterial blood pressure. The results suggest that the lag time of the finger pulse oximeter response is primarily determined by blood flow. PMID- 1306033 TI - Assessment of ankylosing spondylitis. PMID- 1306035 TI - Alcohol in mother's milk. PMID- 1306034 TI - How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. AB - Because economic evaluations of health care services are being published with increasing frequency it is important to (a) evaluate them rigorously and (b) compare the net benefit of the application of one technology with that of others. Four "levels of evidence" that rate economic evaluations on the basis of their methodologic rigour are proposed. They are based on the quality of the methods used to estimate clinical effectiveness, quality of life and costs. With the use of the magnitude of the incremental net benefit of a technology, therapies can also be classified into five "grades of recommendation." A grade A technology is both more effective and cheaper than the existing one, whereas a grade E technology is less or equally effective and more costly. Those of grades B through D are more effective and more costly. A grade B technology costs less than $20,000 per quality-adjusted life-year (QALY), a grade C one $20,000 to $100,000/QALY and a grade D one more than $100,000/QALY. Many issues other than cost effectiveness, such as ethical and political considerations, affect the implementation of a new technology. However, it is hoped that these guidelines will provide a framework with which to interpret economic evaluations and to identify additional information that will be useful in making sound decisions on the adoption and utilization of health care services. PMID- 1306036 TI - The Zavanelli maneuver applied to locked twins. AB - The Zavanelli maneuver was applied to locked twins. After the first infant was returned into the vagina, an emergency cesarean section was performed. After a not-too-good start, both children did well. The Zavanelli maneuver is presented as a method to reverse the potentially catastrophic situation of locked twins. PMID- 1306037 TI - Qualitative holographic study of hemi-pelvic deformation caused by loading different hip prostheses. AB - The dynamic biological response of bone can materially influence the longevity of artificial implants. This paper presents a series of in vitro experiments conducted on epoxy resin models of human hemi-pelves. Different commercially available acetabular components were implanted and used for the construction of simplified three-dimensional models of the artificial hip joint. Boundary conditions included simulation of muscle groups and femoral loading. Real-time holographic interferometry, a stress analysis technique permitting whole-field simultaneous inspection of deformation patterns, was used as the experimental method. The holographic interferograms were interpreted qualitatively rather than quantitatively. High stresses were identified in the hemi-pelvis and it is postulated that these stresses may be implicated in the mechanical pathogenesis of loosening. The observed changes in the detected stress levels could influence both future design of acetabular prostheses and surgical techniques. PMID- 1306038 TI - Specific circulating anti-gliadin IgG-class antibody does not mediate intestinal enteropathy in gliadin-fed mice. AB - The effects of specific circulating IgG antibody on the uptake of dietary antigen and in the generation of intestinal enteropathy have been investigated in Balb/c mice bred on a gluten-free diet. A monoclonal IgG1 antibody (GD3) was prepared against gliadin. After adoptive transfer into mice, this antibody was capable of mediating a type III hypersensitivity response in vivo to footpad challenge with gliadin. The titres of circulating GD3, as estimated in vitro by ELISA, correlated well with the degree of inflammation at sites of type III responses in vivo. Following footpad challenge with gliadin, titres of circulating GD3 antibody were reduced. GD3 antibody was tested for its ability to mediate inflammatory responses in vivo in the intestinal mucosa of mice fed with gliadin. Circulating GD3 antibody was removed selectively and specifically by dietary gliadin, compared to feeding with bovine serum albumin or maintenance on a gliadin-free diet only. However, we were unable to demonstrate any pathological changes in the intestine as a result of possible local antigen-antibody complex formation or deposition. Using radio-iodinated gliadin as a trace marker, no significant retention of gliadin in the intestinal mucosa was found in mice pre injected with GD3 antibody. These data suggest that circulating IgG antibody has little effect on dietary antigen uptake in the gut, and alone is insufficient to mediate an enteropathy. PMID- 1306039 TI - Orbital pseudotumor in the differential diagnosis of pediatric uveitis. AB - Pediatric orbital pseudotumor may be associated with iritis, unlike the adult form of this disorder. However, orbital pseudotumor is seldom considered in the differential diagnosis of childhood uveitis. We report two cases of children with uveitis who were ultimately diagnosed as having orbital pseudotumor. No proptosis was noted in either child. For those pediatric patients with a persistent or recurrent uveitis and a previous negative diagnostic workup, the possibility of an orbital pseudotumor should be considered and ultrasonography, magnetic resonance imaging, and/or computed tomography performed. PMID- 1306040 TI - Large-volume suction lipectomy: an analysis of 108 patients. AB - Suction lipectomy was initially advocated for the treatment of localized collections of fat and for the removal of less than 1500 ml of material. However, many patients wished to have multiple areas treated or had diffuse collections of fat. In such instances, the removal of over 1500 ml of material and circumferential lipectomy are necessary to provide optimal aesthetic results. However, when over 1500 ml of material is removed, anesthetic requirements, fluid replacement, and treatment of blood loss become important if the operation is to be performed safely. We have treated 108 patients who had over 1500 ml of material removed. Eight-eight percent of the patients were female; 12 percent were male. Using the body-mass index, 3 percent of patients were underweight, 70 percent were normal weight, and 27 percent were overweight. Fifty-five patients (51 percent) had 1500 to 2499 ml of material removed, 26 patients (24 percent) had 2500 to 3499 ml removed, 16 patients (15 percent) had 3500 to 4499 ml removed, and 11 patients (10 percent) had over 4500 ml removed. All patients were treated in the hospital; 44 percent were admitted after surgery. A total of 227 units of autologous and 2 units of homologous blood were transfused. As measured by a computerized monitor, the average amount of blood in the material removed from thighs was 30 percent; from abdomens, the blood loss was 45 percent. The aesthetic results were generally excellent. No complications were encountered. A few patients developed undesired sequelae, the most common of which was seroma formation, which occurred in 19 percent of those who had suction of abdominal wall fat. We believe that large-volume suction lipectomy is safe and efficacious, provided attention is directed to such important aspects of patient care as anesthesia, fluid replacement, and blood loss. PMID- 1306041 TI - Efficacy of lignocaine in alleviating potassium chloride infusion pain. AB - A double-blind study was set up to investigate the effect of pretreatment with lignocaine on the incidence of potassium chloride infusion pain. Twenty-eight patients were randomly allocated into two equal groups. Patients in both groups were hypokalaemic and were scheduled for replacement consisting of potassium chloride 20 mmol diluted to 100 ml in dextrose 5% solution administered over two hours. Group A (lignocaine) patients were pretreated with a bolus dose lignocaine 3 ml 1%, Group B (control) received isotonic saline 3 ml. The incidence of potassium chloride infusion pain was significantly reduced in Group A. There was no adverse effect reported. This study demonstrates the efficacy of bolus dose of lignocaine in alleviating injection pain for the duration of a two-hour continuous infusion. PMID- 1306042 TI - Neurobiology of alcohol abuse. AB - Excessive consumption of beverage alcohol (ethanol) is a major health concern worldwide. Understanding the mechanisms by which ethanol affects neural functioning, after both acute and chronic exposure, has become a major goal in the study of alcoholism. With such an understanding, we should be able to institute more effective treatments and preventative measures for alcohol abuse problems. Recent studies have found, contrary to earlier assumptions, that ethanol has selective, dose-dependent effects on various neurotransmitter systems within the CNS. These effects are observed at all levels of analysis, from molecular to behavioral. This review by Herman Samson and Adron Harris covers these recent findings, with the intent of generating questions that will focus further research efforts. PMID- 1306043 TI - National STD trends in Zambia: 1987-89. PMID- 1306044 TI - Chorionic villus sampling: the University of Maryland experience. AB - The University of Maryland was the first program in the state to offer chorionic villus sampling (CVS). Since the program's beginning in 1984, 998 patients have been seen with successful sampling in 99.1 percent, using both transcervical and transabdominal approaches. The overall loss rate was quite low (2.3 percent), and no increased risk of birth defects was seen. These observations demonstrate that CVS provides a safe and accurate alternative to amniocentesis. PMID- 1306045 TI - Care of the normal newborn. PMID- 1306046 TI - Intravenous immune globulin and aseptic meningitis. PMID- 1306047 TI - Where is the evidence? PMID- 1306048 TI - Antigen presentation by Toxoplasma-infected cells: antigen entry through cell membrane fusion. AB - The antigen presentation of cells infected by Toxoplasma gondii (T.g.) for MHC class-I-restricted cytotoxic T cells (CTL) was blocked by treating the T.g. infected cells with the fungal antibiotic brefeldin A. Electron microscopic analysis of T.g.-infected murine and human-antigen-presenting cells (APC) prepared by the combination of quick-freezing with the deep-etching or freeze substitution methods revealed that the outer membrane of T.g. fused with some parts of the vacuolar membranes of APC to build up channel-like structures. Work station and cytofluorometry studies detected 2',7'-bis(carboxyethyl)-5(6) carboxyfluorescein (BCECF) in cells infected by BCECF-labeled T.g., which strongly suggested the direct entry into cells of BCECF derived from T.g. These findings provide evidence that T.g. antigens enter the cytoplasm of APC through cell membrane fusion of T.g. and T.g.-infected APC, and that T.g.-infected APC present T.g. antigen for MHC class-I-restricted CTL through the endogenous pathway of antigen presentation. PMID- 1306049 TI - Assessment of specimen fixation in a surgical pathology service. AB - The quality of specimen fixation was examined within a routine diagnostic histopathology service. For each specimen the adequacy of fixation was assessed and the transit time between operating theatre and the laboratory was measured. Preliminary fixation was found to be inadequate in 25% of specimens and some form of manipulation to assist fixation was required in 36% of specimens. The mean transit time was 22 (SD 10.7) hours. Specimen fixation and transport are additional factors to consider in quality assurance of histopathology. PMID- 1306050 TI - Periodic health examination, 1992 update: 1. Screening for gestational diabetes mellitus. Canadian Task Force on the Periodic Health Examination. PMID- 1306051 TI - Fentanyl and sufentanil increase intracranial pressure in head trauma patients. AB - Although opioids frequently are administered to patients with severe head trauma, the effects of such drugs on intracranial pressure are controversial. Nine patients with severe head trauma were studied for the effects of fentanyl and sufentanil on intracranial pressure (ICP). In all patients, ICP monitoring was instituted before the study. Full neuromuscular blockade was achieved with vecuronium bromide before the administration of either fentanyl (3 micrograms.kg 1) or sufentanil (0.6 microgram.kg-1) as an intravenous bolus over a 1-min period in a masked and random fashion. Patients received the other opioid in the same fashion 24 h later. Arterial blood pressure, heart rate, and ICP were recorded continuously for the 1 h after drug administration. Fentanyl was associated with an average ICP increase of 8 +/- 2 mmHg, and sufentanil with an increase of 6 +/- 1 mmHg. These increases were statistically significant. Both drugs produced clinically mild decreases in mean arterial blood pressure (fentanyl, 11 +/- 6 mmHg; sufentanil, 10 +/- 5 mmHg) that nevertheless were statistically significant. No significant changes in heart rate occurred. These results indicate that modest doses of potent opioids can significantly increase ICP in patients with severe head trauma. PMID- 1306052 TI - Second-look laparoscopy after laparoscopic cystectomy of large ovarian endometriomas. AB - Forty-two patients who underwent a second-look laparoscopy after a unilateral or bilateral intraperitoneal cystectomy for treatment of an ovarian endometrioma of greater than 3 cm were included. At second-look laparoscopy, 92.4% of the adnexae treated for a large endometrioma had no deep ovarian endometriosis. Adhesion de novo formation occurred in 21% of the treated adnexae and in 17% of the contralateral adnexae. Complete or partial recurrence of dense adhesions occurred in 82% of the cases. Laparoscopic cystectomy is effective in treating large endometriomas. However, operative difficulties may be encountered, explaining persistent endometriomas and postoperative adhesions. PMID- 1306053 TI - Exogenous control of the cycle simplifies thawed embryo transfer and results in a pregnancy rate similar to that for natural cycles. AB - To determine if a satisfactory PR could be achieved in thawed ET using a simplified protocol, standard monitoring in the natural cycle was compared with a controlled preparation of the endometrium with exogenous E2 and P without hormonal or ultrasonographic monitoring. All patients had normal ovarian function, and no GnRH-a were administered. Pregnancy rates, ongoing PRs, and embryo implantation rates were similar in the two groups. The use of exogenous E2 and P without GnRH-a suppression to control the cycle for thaw ET is safe, convenient, and results in PRs at least as good as in the natural cycle. It may be of particular value in patients with an irregular cycle or in those for whom prolonged monitoring is undesirable. PMID- 1306054 TI - A simple technique for oxygen analysis during provision of supplemental oxygen during regional or local "MAC" cases. PMID- 1306055 TI - Long-term complications of native valve infective endocarditis in non-addicts. A 15-year follow-up study. AB - OBJECTIVE: To describe the incidence and clinical manifestations of long-term cardiac complications of endocarditis. DESIGN: Cohort study. SETTING: University affiliated tertiary medical center. PATIENTS: One hundred twelve consecutive patients, survivors from a series of 140 non-addicted patients with a first episode of infective endocarditis on native valves hospitalized from 1975 to 1990. Thirty-two patients had had valve replacement during the active phase of the infection, and the remaining 80 patients received medical treatment alone. MEASUREMENTS: Relapse, recurrence, need for late cardiac surgery, and cardiac mortality. RESULTS: Relapses occurred in three patients (2.7%) and recurrences in five patients (4.5%, incidence density at 15 years, 0.0030 per patient-year). Late cardiac surgery was needed by 47% of the patients treated medically during the active phase, and most had surgery in the first 2 years of follow-up (incidence density, 0.25 per patient-year at 2 years). Aortic valve involvement (relative risk, 2.66; 95% CI, 1.15 to 6.17) and end-diastolic diameter greater than 60 mm (relative risk, 1.04; 95% CI, 1.03 to 2.43) were associated with the need for late surgery in univariate analysis. Multiple logistic regression analysis showed aortic valve involvement to be an independent predictor of the need for late surgery (relative risk, 3.04; CI, 1.23 to 7.54). Only 2 of the 32 patients who had surgery during the active infection needed a second operation during follow-up. At the end of follow-up, the number of patients who had surgery after the onset of the infection was 86 (60% of the whole series). Cardiac death occurred in 16 patients; most deaths were sudden or postoperative and occurred in the first 2 years of follow-up (incidence density, 0.047 per patient-year at 2 years). Independent predictors of death were not found. Survival was 90% at 2 years, 88% at 5 years, 81% at 10 years, and 61% at 15 years. CONCLUSIONS: Survival after infective endocarditis is fair (81% probability of survival at 10 years), and the most common types of cardiac death are sudden and postoperative. Aortic valve involvement is an independent predictor of the need for late cardiac surgery. The rate of recurrences is not negligible (incidence density at 15 years, 0.0030 per patient-year). PMID- 1306056 TI - How safe is safe enough? New infections and the U.S. blood supply. PMID- 1306057 TI - The diagnosis and initial management of head injury. PMID- 1306058 TI - Learning fibreoptic intubation: fundamental problems. PMID- 1306059 TI - Prolonged resuscitation in acute deep hypothermia. AB - A case report is described with successful outcome of prolonged cardiopulmonary resuscitation in a 30-year-old man suffering from acute deep hypothermia. His lowest temperature recorded was 23 degrees C. Continuous external cardiac massage was required for a total of 4.5 h whilst rewarming was instituted. The patient eventually left hospital with no permanent sequelae. A review of hypothermia follows, emphasising some important management principals and pitfalls. PMID- 1306060 TI - Ventricular standstill complicating left heart catheterization in the presence of uncomplicated right bundle branch block. AB - We report the unusual occurrence of complete heart block during attempted right coronary artery cannulation in a patient with pre-existing uncomplicated right bundle branch block (RBBB). This complication occurred due to accidental impingement of the Judkin's right coronary catheter on the left bundle when it transiently slipped across the aortic valve. The block resolved without any complication. PMID- 1306061 TI - A piece of my mind. Calling Dr Doctor. PMID- 1306062 TI - Simultaneous reconstruction of the abdominal aorta and cholecystectomy. A peer review perspective. PMID- 1306063 TI - The case for chemonucleolysis in discogenic sciatica. A review. PMID- 1306064 TI - The risk of needlestick injuries and needlestick-transmitted diseases in the practice of anesthesiology. AB - Anesthesiologists are at risk for acquiring blood-borne infections through contact with blood or body fluids. From prospective studies, the greatest risk of transmission is through a percutaneous exposure such as needlestick injury. Personal protective equipment such as gloves and gowns do not completely prevent these exposures. Although educational efforts can reduce the frequency of recapping of needles, they generally have not decreased the incidence of needlesticks. Therefore, in addition to practicing universal precautions, anesthesiologists can attempt to reduce their risk of needlestick injuries by eliminating nonessential unprotected needle use, through the use of needleless or protected needle devices (engineering controls) and by modifying anesthetic procedures requiring needles (work practice controls). Needleless or protected needle products are commercially available for use in many procedures performed by anesthesiologists. For tasks that require the use of needled devices, the practitioner should use safe techniques for handling (i.e., one-handed recapping if recapping is needed) and disposal (i.e., puncture-resistant containers) of these devices. Evaluation of the efficacy, cost, and safety of needleless or protected needle products should be continued as they are introduced into wider use. Additionally, anesthesiologists should be encouraged to report needlestick injuries so that appropriate postexposure treatment can be given and so that the incident can be studied to permit design of a work protocol or device to prevent similar accidents in the future. PMID- 1306065 TI - Overwhelming postsplenectomy infection still a problem. AB - Despite an extensive medical literature over the past ten years, patients continue to die needlessly of overwhelming postsplenectomy infection. Although physicians have become increasingly cognizant of this syndrome in children, many remain unaware of the risk to asplenic or hyposplenic adults with no underlying medical problems. In addition, many older asplenic or functionally hyposplenic persons are unaware that they are at risk for this syndrome. The identification of Howell-Jolly bodies on a peripheral blood smear should alert physicians to the need for further follow-up to establish hyposplenism and to consider possible antipneumococcal vaccination. PMID- 1306066 TI - An interview with Nancy L. Johnson and Patricia Schroeder. Interview by Carmella A. Bocchino. AB - In the U.S. Congress--440 members in the House and 100 members in the Senate- only 31 are women (29 House and 2 Senate members). This year over 100 women are seeking seats in the Congress, many are campaigning for governor, and still others are running for state and local offices. Women candidates are generally seen as outsiders who symbolize change and inspire a new vision for the future. This interview highlights two incumbent members of the House of Representatives, Nancy L. Johnson (R-CT) and Patricia Schroeder (D-CO), and their views on women's health, family medical leave, and future changes in the U.S. health care system. PMID- 1306068 TI - Perianal zygomycosis in paroxysmal nocturnal haemoglobinuria. PMID- 1306067 TI - Gene therapy. Harkin seeks compassionate use of unproven treatments. PMID- 1306069 TI - Childhood asthma: update. PMID- 1306070 TI - Precision of the time-domain correlation ultrasonic flowmeter. PMID- 1306071 TI - Histologic study of chronic active hepatitis C; comparison with chronic active hepatitis B. AB - Reports on the histologic findings of chronic active hepatitis C (CAH-C) have been rare, and the characteristic histologic findings of CAH-C have been not yet determined. To compare the differences in the histologic findings between CAH-C and chronic active hepatitis B (CAH-B) group, we analyzed the histologic findings of 19 patients with CAH-C, who had positive tests for HCV-antibody by EIA, and 19 patients with CAH-B who had negative tests for HCV-antibody but positive tests for HBsAg by RIA. Histologic features were analyzed between the CAH-C and CAH-B groups using a scoring system which is modified from Knodell's histologic activity index-looking at portal inflammation, periportal necroinflammation, portal fibrosis, focal necrosis, regeneration, polyploid nuclear change, sinusoidal lymphocytic reaction and fatty change. Portal inflammatory cell infiltrations with prominent lymphocytes and follicular arrangement were more frequent in the CAH-C group (10 of 19 cases) than in the CAH-B group (5 of 19 cases). Severe sinusoidal lymphocytic reactions were also more prominent in the CAH-C group (11 of 19 cases) than in the CAH-B group (6 of 19 cases). However, periportal necroinflammation, portal fibrosis, focal hepatic necrosis, regeneration and polyploid nuclear changes were more prominent in the CAH-B group than in the CAH-C group. In conclusion, follicular portal inflammation and severe sinusoidal lymphocytic reactions were common histologic findings in serologically proven CAH-C when compared to CAH-B. PMID- 1306072 TI - Effects of buthionine sulfoximine treatment on cellular glutathione levels and cytotoxicities of cisplatin, carboplatin and radiation in human stomach and ovarian cancer cell lines. AB - Chemotherapy failure remains a significant medical problem in the treatment of neoplastic disease and is thought to be due to many different factors including membrane transport, p-glycoprotein in multidrug resistance, glutathione and its related enzymes, topoisomerase II and DNA repair. Glutathione is a major constituent of non-protein thiol and participates in detoxification of chemotherapy and radiation. Thus, glutathione concentration is correlated with sensitivity to alkylating agents and radiation, and increased in resistant cell lines. Buthionine sulfoximine (BSO) is an inhibitor of glutathione biosynthesis and may increase cytotoxicities of alkylating agents, including melphalan and cisplatin, and radiation in sensitive and resistant cell lines. We studied effects on cellular glutathione levels and cytotoxicities of cisplatin, carboplatin and radiation by BSO treatment in human stomach cancer cell line (SNU 1) and ovarian cancer cell line (OVCAR-3). The results were as follow: 1) After BSO treatment of 1 mM and 2 mM for 2 days, the intracellular thiol concentration was depleted to 75.7% and 76.2% in SNU-1, and 74.1% and 63.0% in OVCAR-3, respectively. 2) The intracellular thiol concentration in SNU-1 was depleted to 33.4% after BSO 2 mM for only 2 hours incubation and 71.5% after small amount of BSO (0.02 mM) for 2 days. 3) The recovery of intracellular thiol concentration required more than 3 days after BSO removal. 4) BSO inhibited partially the growth of SNU-1 and OVCAR-3. 5) The cytotoxicities of cisplatin and carboplatin were markedly enhanced both in SNU-1 and OVCAR-3 by BSO treatment. 6) The cytotoxicities of radiation was increased in OVCAR-3 and SNU-1 by BSO treatment. Therefore, it is concluded that BSO can deplete effectively the intracellular thiol concentration and enhance the cytotoxicities of cisplatin, carboplatin and radiation. PMID- 1306073 TI - Effect of periodic transfusion on erythropoietin concentration in end stage renal disease. AB - BACKGROUND: It has been reported that a feedback circuit exists between erythropoietin (EPO) concentration and the degree of anemia even in end stage renal disease (ESRD), and growing experience with subcutaneous EPO administration confirms that only slight increases in EPO levels are required to correct renal anemia. Keeping in mind these findings, if a small portion of reserved EPO production could be reactivated in ESRD, it might be biologically significant and vice-versa. From this viewpoint, it is conceivable that periodic long term transfusion might suppress EPO production in ESRD. METHODS: In order to see whether periodic transfusion influences the EPO concentration in ESRD, a cross sectional retrospective study was undertaken by reviewing medical records of 28 non-transfusion patients and 22 transfusion patients with ESRD undergoing hemodialysis. RESULTS: The EPO concentration of the ESRD group (29.1 +/- 8.0 mU/ml) but only about one twentieth of the control group (578.8 +/- 69.1 mU/ml). In ESRD group, It was 27.9 +/- 8.0 mU/ml in transfusion group and 30.6 +/- 7.9 mU/ml in non-transfusion group. EPO concentration at varying hematocrit (Hct) levels did not differ between the non-transfusion group and transfusion group. There was an inverse relationship seen in the non-transfusion group (p < 0.05) but no relationship was seen between the EPO concentrations and varying Hct levels in the transfusion group. The EPO concentration at equal levels of Hct did not differ between the non-transfusion group and transfusion group. The relationship between EPO concentration and the changes in Hct during the observation period did not differ between the non-transfusion group and transfusion group. Both the total amount of transfusion and the frequency of transfusions did not influence EPO concentration. CONCLUSION: periodic long term transfusion does not seem to decrease the sensitivity of the EPO producing cell to the degree of anemia in ESRD. PMID- 1306074 TI - Effect of probenecid on tetraethyl ammonium (TEA) transport across basolateral membrane of rabbit proximal tubule. AB - The effect of probenecid on the transport of tetraethylammonium (TEA) was investigated in rabbit reanal cortical slices in an attempt to ascertain the interaction of organic anion with the organic cation transport system in proximal tubule. Probenecid reversibly inhibited TEA uptake by cortical slices in a dose dependent manner over the concentration range of 1 and 5 mM. The efflux of TEA was not affected by the presence of 3 mM probenecid. Kinetic analysis indicated that probenecid decreased Vmax without a significant change in Km. Probenecid inhibited significantly tissue oxygen consumption at concentrations of 3 and 5 mM. However, probenecid did not significantly reduce TEA uptake in brush border and basolateral membrane vesicles prepared from renal cortex even at higher concentration of 10 mM. These results indicate that probenecid reduces TEA uptake in cortical slices by inhibiting the tissue metabolism rather than by the interaction with the organic cation transporter. PMID- 1306075 TI - The effect of dilution, pH and ionic strength of plasma on t-PA precipitation in euglobulin fraction. AB - In order to evaluate the influence of dilution, pH and ionic strength on the precipitation of t-PA and PAI-1 during euglobulin precipitation, we measured t-PA Ag, PAI-1 Ag and fibrinolytic activity in the euglobulin fraction made of pooled plasma from liver cirrhosis patients, under various conditions by changing pH, ionic strength and degree of dilution. The precipitation of t-PA Ag in the euglobulin fraction was enhanced by decreasing the ionic strength and greatest at pH 6.0. The fibrinolytic activity in the euglobulin fraction showed consistent changes with t-PA Ag under varying pH and ionic strength. The precipitation of t PA Ag was not influenced by the dilution factor but the larger the dilution factor, the greater the PAI-1 and the smaller the fibrinolytic activity in the euglobulin fraction. PAI Ag in euglobulin fraction showed consistent changes with t-PA Ag in the euglobulin fraction regardless of the changes in ionic strength and pH. The amount of precipitation of t-PA and PAI-1 was increased by the presence of dextran sulfate, under varying pH, ionic strength and dilution conditions. Our results show that the currently used conditions for standard euglobulin precipitation are the most favorable for t-PA precipitation into the euglobulin fraction. The fibrinolytic activity exerted in the euglobulin fraction seems to depend on the amount of t-PA-PAI-1 complex rather than minimized protease inhibitor in the euglobulin fraction. PMID- 1306076 TI - Plasma t-PA and PAl-1 antigen concentrations in non-insulin dependent diabetic patients: effects of treatment modality on fibrinolysis. AB - Basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAl-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women: ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean t-PA antigen (5.15 +/- 3.02 vs 3.20 +/- 2.30 ng/ml) and PAl-1 antigen (35.89 +/- 18.59 vs 17.60 +/- 15.36 ng/ml) levels (p < 0.05). Plasma t-PA antigen level was not influenced by each treatment modality. There was a significant decrease of plasma PAl-1 antigen level after Metformin administration compared to that of before Metformin administration (39.74 +/- 19.39 vs 25.14 +/- 16.18 ng/ml) (p < 0.05), and the insulin-treated group showed a tendency for a decrease of plasma PAl-1 antigen levels after insulin administration but this did not reach statistical significance (29.93 +/- 15.37 vs 17.32 +/- 10.60 ng/ml). Sulfonylurea did not change both plasma t-PA and PAl-1 antigen levels. In conclusion, diabetic patients have high t-PA and PAl-1 antigen levels. Biguanide reduced plasma PAl-1 antigen levels, which might play some helpful role in the improvement of chronic complications in NIDDM. PMID- 1306079 TI - [Irrigation of the brain and the extremities, and left ventricular performance in football players]. PMID- 1306077 TI - Small airway disease in rheumatoid arthritis. AB - Variety of pulmonary lesions are thought to be associated with rheumatoid arthritis (RA). These lesions traditionally have included pleurisy with or without effusion, Caplan's syndrome, pulmonary rheumatoid nodules, diffuse interstitial fibrosis, and pulmonary arteritis and hypertension. But little attention has been paid to the airways in RA. Recently, several reports have suggested an association between airflow limitation and RA, but its incidence is not known. Also whether there exists a parameter of disease activity of RA, suggesting the presence of small airway disease (SAD) is not clear. To answer these questions, the serologic parameters which reflect the disease activity of RA and pulmonary function tests which reflect small airway dysfunction were performed on 36 lifetime nonsmokers with RA who had normal chest x-ray findings. The prevalence of SAD and the relationships between the disease activity parameters of RA and pulmonary function were observed. The results were as follows. The percentages of patients with abnormal values for diffusing capacity, frequency dependence of compliance (C1.0/C0.0), forced expiratory flow 25-75%, Vmax50% and Vmax 75% were 45.5%, 62.5%, 40%, 22.8% and 11.4%, respectively. There was statistically significant negative correlation between C1.0/C0.0 and ESR. But consistent correlation between other pulmonary function tests and clinical and serologic parameters of RA, and differences in pulmonary function between patients who were serologically positive and negative for CRP and FANA, were not found. In conclusion, SAD, without the influence of smoking, is frequently associated with RA, but the presence of SAD cannot be predicted from any clinical and serologic parameters of RA currently in use. PMID- 1306078 TI - Evaluation of finger blood flow with Tc-99m MDP (methylene diphosphonate). AB - BACKGROUND: A variety of methods were used to establish objective diagnostic criteria of Raynaud's phenomenon. We intended to introduce another method, using radionuclide (Tc-99m methylene diphosphonate) scintigraphy, which is more objective, simple and economical than the past methods. METHODS: The finger blood flow with radionuclide scintigraphy was evaluated in 10 patients of Raynaud's syndrome, 12 patients of connective disease without Raynaud's symptoms, and 20 normal persons. After immersing one hand in ice water (4 degrees C) for 30 seconds, the hand was exposed to 22 degrees C room air for 15 minutes, and then the patients received the intravenous (IV) bolus of 20 microCi of Tc-99m methylene diphosphonate (MDP). At the same time, scintigraphic image of both hands started with the region of interest, including the second, third, fourth and fifth fingers distal to the metacarpophalangeal (MCP) joints. Computer recording of the counts in the region of interest every 2 seconds for 310 seconds was started on IV bolus injection. RESULTS: The 310 seconds cumulative digital blood flow ratio of cold exposed hand to room air exposed hand was significantly lower in Raynaud's group (p < 0.001), and the ratio of initial slope of activity curve was also lower in the Raynaud's group (p < 0.001). Of the 8 patients showing Raynaud's syndrome, 4 patients of scleroderma and 1 patient of multiple myeloma showed no improvement of finger blood flow in the cold exposed hand after 2 weeks of pharmacological therapy, but 1 patient of mixed connective tissue disease, 1 patient of Behcet's syndrome and 1 patient of SLE showed much improved finger blood flow after combined administration of vasodilator, calcium channel blockers and antiplatelet drugs. CONCLUSIONS: The evaluation of finger blood flow with 99mTc-MDP could be considered to be one of the simple, economical and new methods that can be used in the follow-up, objective assessment of therapeutic effect, and giving an aid in the study of the pathophysiology of the Raynaud's phenomenon. PMID- 1306080 TI - [Physiopathology of silent myocardial ischemia]. PMID- 1306081 TI - [Myocardial-coronary morphofunctional changes in diabetes mellitus]. PMID- 1306082 TI - Role of the epithelial derived factors on airway reactivity. AB - A tracheobronchial smooth muscle reactivity study on isolated guinea pig tracheal rings was done. The existence of two different factors active on the smooth muscle, an inhibiting one as well as an activating one were identified. Generated on different pathways, the epithelial derived relaxing factor is a cyclooxygenase dependent prostaglandin, while the activating epithelial factor seems to be a thromboxane derivative. PMID- 1306083 TI - Phagocytic response in rats following chemical sympathectomy with 6 hydroxydopamine. AB - Wistar rats were injected i.p. at 2, 4 and 7 days after birth with 6-OHDA (50 mg/kg). At maturity the phagocytic response of neutrophils was elicited by Escherichia coli (EC) lipopolysaccharide (LPS). Before and at 3 and 24 hours after the injection of LPS (1 mg/kg i.v.) the leucocyte (L) and neutrophil (N) counts and the phagocytic activity of N in blood against EC have been tested. In controls (6 female and 7 male rats) the number of N increases significantly after 3 h. The L and N responses were similar in controls and in treated (SyX) animals. In controls the percentage of phagocytic active N(PA) and the number of bacteria incorporated by 100 n(IB) shows significant rises at 3 h. In the SyX groups (7 females and 7 males) PA does not increase; the IB decreases significantly in females at 3 and 24 h. In conclusion chemical sympathectomy depresses the PR to LPS in rats; this suggests a stimulatory action of the sympathetic system on the phagocytic immune reaction. An immunological sexual dimorphism exists. PMID- 1306084 TI - Studies regarding the efficiency of Supro isolated soy protein in Olympic athletes. AB - 66 Romanian olympic endurance athletes (30 kayak-canoe, 36 rowing; 45 males and 21 females) participated in our trial, for the purpose to make evident possible biological effects of Supro isolated soy protein supply (1.5 g/kg/day, 8 weeks). At random the athletes were divided into two groups: A group (n = 38) and B group (n = 28). Daily programme (4-6 hours daily, endurance and strength), food and medication were similar for all athletes. The athletes of the A group received daily 1.5 g/kg SuproR soy protein, for 8 weeks while the athletes of the B group did not received soy protein supply. Two months soy protein supply induced increases of body mass (about 3 kg, especially by lean body mass), strength indexes, serum proteins, haemoglobin and total calcium and significant decreases of urinary mucoproteins and fatigue after training sessions, especially when comparing to the athletes of the B group. No damages of liver, kidney and metabolism tests were noticed in all athletes; no side effects were noticed and the product was well tolerated by athletes. When applying the cross-over method for other 2 months we obtained the same results. Based on these data the authors support the idea of a beneficial effect of this soy protein supply on the biological preparation of endurance top athletes. PMID- 1306085 TI - [Experimental studies on the sedative-tranquilizing action of nifedipine]. PMID- 1306086 TI - The stimulation of fibronectin synthesis by high peak power electromagnetic energy (Diapulse). AB - The effect of Diapulse therapy (pulsed electromagnetic energy of 27.12 MHz frequency) on post-operative wound healing and plasma fibronectin concentration is investigated. Patients treated with Diapulse, locally and over hepatic area present higher fibronectin levels starting 3d day after surgery. These higher values correlate well with a clear improvement of wound healing processes. PMID- 1306087 TI - The MSH-like activity of pineal hormone E5 in vivo and in vitro experiment. AB - Further experiments have revealed that the polypeptidic hormone E5 has a MSK-like effect, as experimentally demonstrated on the frog skin. In Rana esculenta, 30 120 min after a subcutaneous injection of 0.2 mg purified E5B or E5P/100 g b.w., the skin blackened and the effect lasted for about two hours. A comparable effect was induced by incubating the fragment of frog abdominal skin with a similar solution of E5. This MSK-like effect appears to be identical upon mammalian melanocytes in C57/B16 mice strain valves in vitro experiment. The results obtained indicate that pineal gland can influence melanocyte activity directly and suggest the possible implication in such pathological conditions as melanomas, vitiligo, etc. PMID- 1306088 TI - The action of Cu2+ on the frog epithelium. AB - The mechanism of action of Cu2+ when applied to the external side of the frog skin preparation was investigated. Cu2+ acts most probably on the external barrier of this preparation, since it increases the transport pool of Na proportionally to the increase in the short-circuit current (I(sc)). Cu2+ does not open new routes for the Na+ entry since the stimulated I(sc) is still completely abolished by amiloride. The I(sc) dependence of Na concentration in the external medium is modified by cooper, since the Ksm value increases in addition to changes in I(sc). PMID- 1306089 TI - [The value of aminoaciduria in the prognosis of the risk that the newborn will develop rickets, mental disability or other neurologic disorders]. PMID- 1306090 TI - [Irrigation of the extremities in young people with Raynaud's syndrome]. PMID- 1306091 TI - Ethnic differences in the lung cancer risk associated with smoking. AB - Mortality trends and ecological data strongly suggest that the lung cancer risk associated with smoking is greater among Hawaiians than among the other ethnic groups in Hawaii. The authors combined data from two consecutive population-based case-control studies to formally test this hypothesis among 740 cases and 1616 controls. A multiple logistic regression analysis adjusting for pack-years of smoking, occupation, education, and age revealed that Hawaiian, Filipino, and Caucasian male smokers were at 121%, 53%, and 46% greater risk for lung cancer than Japanese male smokers. These risk differences were statistically significant, were consistent across sexes and histological types, and were not explained by the type of cigarettes, the level of inhalation, or by cholesterol or beta-carotene intake. Additionally, an increased lung cancer risk unrelated to smoking was observed among Chinese women. The possibility that other dietary antioxidants and/or genetic risk factors are responsible for these ethnic differences needs to be investigated. PMID- 1306092 TI - Risk factors for stomach cancer in sixty-five Chinese counties. AB - Stomach cancer mortality data were compared with dietary and biochemical data from 65 Chinese counties to provide clues to reasons for the marked geographic variation of stomach cancer mortality rates in China. Sex-specific correlation and multivariate regression analyses showed significant positive associations with consumption of salted vegetables and eggs, prevalence of antibodies to Helicobacter pylori, and levels of plasma albumin; and significant negative associations with intake of green vegetables and levels of plasma selenium and beta-carotene. Limitations of ecological data preclude causal inferences, but these findings suggest factors that may contribute to making stomach cancer the leading cause of cancer death in China and other countries. PMID- 1306093 TI - Folate, vitamin C, and cervical intraepithelial neoplasia. AB - A case-control study was designed to assess the relationship between cervical intraepithelial neoplasia (CIN) and folate in serum, red blood cells, and diet. The association between CIN and dietary vitamin C was also investigated. Cases were selected from women with biopsy-confirmed CIN. Controls were age-, race-, and clinic-matched women with normal cervical (Pap) smears. Study participants completed self-administered food frequency (n = 100 matched pairs) and health (n = 102 matched pairs) questionnaires. Fasting venous blood samples were collected for serum (n = 98 matched pairs) and red cell (n = 68 matched pairs) folate assays. Conditional logistic regression models were used to estimate crude odds ratios and odds ratios adjusted for smoking, income, number of sexual partners, frequency of cervical smear, use of spermicidal contraceptive agents, history of genital warts, and Quetelet index. Dietary intake variables were adjusted for total energy intake prior to logistic regression. A protective effect of red cell folate was evident with adjusted odds ratios (95% confidence intervals) of 0.1 (0.0-0.4), 0.6 (0.2-2.0), and 0.5 (0.2-1.9) for those in quartiles 4 (highest), 3, and 2 compared to quartile 1 (lowest). Supporting evidence for the protective effect of folate was provided by inverse associations between CIN and folate in both serum and diet. An inverse association was also found between CIN and dietary vitamin C with adjusted odds ratios (95% confidence intervals) of 0.2 (0.0-0.7), 0.6 (0.2-1.6), and 0.6 (0.2-1.8) for those in quartiles 4, 3, and 2, respectively, compared to quartile 1. These findings support dietary recommendations, such as those of the American Cancer Society, the National Cancer Institute, and the U.S. Dietary Guidelines, which allow for adequate intake of folate and vitamin C, both of which are found in good quantity in fruits and vegetables. Increased consumption of legumes and whole grains is also in accord with current dietary recommendations, and both of these types of foods are good sources of folates. PMID- 1306094 TI - Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers. AB - Although epidemiological studies suggest that cigarette smoking is a risk factor for cervical cancer, further evidence is required to document the biological plausibility of this relationship. This study obtained cervical mucus, using a cervical flush technique, from 50 patients in a neoplasia clinic. Nicotine was detected in the cervical mucus of all 25 smokers and cotinine in the mucus of 84% of the smokers; nicotine and cotinine levels were correlated (P < or = 0.10) with both the number of cigarettes usually smoked and the number smoked in the last 24 h. Nicotine and cotinine levels for passive smokers and nonexposed women were much lower than for women who currently smoked, with little difference found between the nonsmoking women who did and did not report passive smoke exposure. In the one woman who reported smokeless tobacco use, both nicotine and cotinine were detected at much higher levels than for other nonsmoking women. These results indicate that tobacco constituents do indeed reach the uterine cervix, suggesting that they could play a causal role in the development of cervical cancer. PMID- 1306095 TI - Polyamine contents in rectal and buccal mucosae in humans treated with oral difluoromethylornithine. AB - Difluoromethylornithine (DFMO) is an investigational chemopreventive agent that inhibits ornithine decarboxylase (ODC) activity, lowers cellular polyamine concentrations, and decreases cell proliferation in vivo and in vitro. In five subjects we have compared the polyamine concentrations in rectal mucosal biopsies and in exfoliated buccal mucosal cells (EBM) before and after DFMO treatment to assess the suitability of EBM as an easily accessible marker tissue for DFMO suppression of polyamine synthesis in the rectal mucosa. One month of 3 g/m2/day of DFMO treatment caused a statistically significant decrease in putrescine and spermidine concentrations in rectal mucosa biopsy specimens but not in EBM samples. ODC activity in EBM was high (approximately 1 mumol/min/mg protein), resistant to DFMO inhibition (Ki = 4200 microM), dependent on GTP concentration (maximal at 0.1 mM), and was reduced concomitantly with bacterial concentration by antiseptic mouthwashing. Bacteria adherent to EBM were visible by electron microscopy. Forty bacterial colonies/ng protein were culturable from washed EBM samples. Oral bacteria preclude the use of EBM samples as a marker tissue of DFMO effect in the rectal mucosa, but oral DFMO therapy is effective in depleting polyamines in rectal mucosa. PMID- 1306096 TI - Expression of the CYP1A1 gene in peripheral lymphocytes as a marker of exposure to creosote in railroad workers. AB - We have conducted a pilot study to assess levels of cytochrome CYP1A1 gene expression in human peripheral lymphocytes as a molecular biomarker assay for polycyclic hydrocarbon exposure. Basal and 3-methylcholanthrene-induced levels of gene expression were measured by standard slot-blot mRNA analyses in mitogen stimulated cultures of peripheral blood lymphocytes from creosote-exposed railroad workers and unexposed control subjects. Dermal and inhalation exposure of workers to creosote may vary substantially as a function of working conditions related to temperature. Therefore, blood specimens were collected from separate groups during the winter, fall, and summer. Basal and induced CYP1A1 gene expression levels were not elevated in workers from any of the three seasonal studies. However, induced/basal (inducibility) CYP1A1 mRNA ratios from workers sampled in the summer (when actual exposures were greatest) were significantly higher when compared to those of controls (P < 0.01). These studies demonstrate the potential usefulness of specific gene expression assays in human peripheral lymphocytes for the assessment of carcinogen exposure in human populations. PMID- 1306097 TI - Identification of women at increased risk for breast cancer in a population-based screening program. AB - A multivariate model to assess breast cancer risk was developed by Gail et al. (M. H. Gail, L. A. Brinton, D. B. Byar, D. K. Corle, S. B. Green, C. Schairer, and J. J. Mulvihill, J. Natl. Cancer Inst., 81: 1879-1886, 1989) based on data analysis of the Breast Cancer Detection and Demonstration Project. We evaluated the model's usefulness for assigning women to risk groups for counseling and follow-up by applying it to the 1987 Texas Breast Screening Project data. We identified 3165 women with one or more first-degree relatives affected with breast cancer. The mean risk score for the group was 3.3 (range, 2.7-11.8), indicating a greater than 3-fold elevated risk. The mean risk score for the remaining 27,439 women without affected first-degree relatives was 1.5 (range, 1.24-3.2). Risk perception was found to be a motivator for participation. Women with a risk score greater than 5 perceived themselves to be at high risk for breast cancer. The perception of risk was related to the type of affected first degree relatives: 80.0% of the women with three affected first-degree relatives and 71.5% of women whose mother and sister were both affected with breast cancer perceived themselves to be at high risk. The Gail model is potentially useful in the clinical setting because women at high risk for breast cancer can be entered into etiological studies, enrolled in primary prevention trials, or referred to programs seeking to improve compliance with screening mammography. The Gail model needs validation, but it is useful for estimating the risk of breast cancer in large populations. PMID- 1306098 TI - Epidemiological models of carcinogenesis: the example of bladder cancer. AB - Epidemiological studies have clearly shown that smokers have an increased risk of bladder cancer. Chemical, biochemical, and molecular investigations indicate that such risk might be due to aromatic amines which are present in tobacco smoke. In particular, collaborative studies have shown that smokers have increased levels of hemoglobin-4-aminobiphenyl adducts in their blood and that these levels show a dose-response relationship and an association with the most carcinogenic variety of tobacco, air-cured or black tobacco. Adduct concentrations were also modulated by the genetically based slow acetylator phenotype. In addition, investigations in dogs and humans have described a DNA adduct in bladder biopsies and in exfoliated bladder cells that is a derivative of 4-aminobiphenyl. This paper summarizes the epidemiological, biochemical, and molecular evidence concerning the possible mechanisms of bladder cancer induction in smokers and in occupationally exposed workers. The case of bladder cancer is an example of integration between epidemiological studies, mathematical modeling, and laboratory investigations aiming at the elucidation of mechanisms of carcinogenesis. PMID- 1306099 TI - Retinoids and carotenoids in the prevention of oral cancer: a critical appraisal. PMID- 1306101 TI - Poverty and cancer. PMID- 1306100 TI - The new cancer prevention and control. PMID- 1306102 TI - HLA and multiple myeloma among black and white men: evidence of a genetic association. AB - To evaluate the possibility that genetic factors contribute to the excess rates of multiple myeloma among blacks, serological typing of human leukocyte antigens (HLA) was conducted for black and white male patients and controls who participated in a large population-based case-control interview study. Forty-six black cases, 88 black controls, 85 white cases, and 122 white controls were typed for the Class I antigens (HLA-A, -B, -C) and for the Class II antigens (HLA-DR, HLA-DQ). Black cases had significantly higher gene frequencies than black controls for Bw65, Cw2, and DRw14, while white cases had higher gene frequencies than white controls for A3 and Cw2 and blanks at the DR and DQ loci. Further analysis of the association between Cw2 and multiple myeloma revealed relative risks of 5.7 (95% confidence interval = 1.5-26.6) and 2.6 (95% confidence interval = 1.0-7.2) for blacks and whites, respectively. The frequency of Cw2 in black and white controls was similar. These findings suggest that the Cw2 allele enhances the risk of myeloma in blacks and whites but do not explain the higher incidence of this cancer among blacks. The study also suggests that undefined DQ antigens may play an etiological role, supporting the need for further research into the immunogenetic determinants of myeloma. PMID- 1306103 TI - Is histological subtype a marker for environmental exposures in acute myelogenous leukemia? AB - The association between occupational and other environmental exposures was evaluated in 60 acute myelogenous leukemia cases and controls. Odds ratios and 95% confidence intervals for prior cytotoxic therapy and benzene exposure, adjusted for age, sex, and race by logistic regression, were 3.7 (0.7, 19.9) and 2.6 (0.4, 15.2), respectively. No other work-related associations, including employment in electrical occupations, were present. Other associations were suggestive but may have been due to biases in control selection or small numbers of subjects. The risks for prior cytotoxic therapy (odds ratio = 10.2) and benzene exposure (odds ratio = 11.4) were concentrated in 13 patients with French American-British M4 leukemia; no environmental exposures were associated with French-American-British subtypes M1 and M2. These findings support the concept that French-American-British histological subtypes of AML may have different etiologies. PMID- 1306104 TI - A prospective comparison of prostate cancer at autopsy and as a clinical event: the Hawaii Japanese experience. AB - Prostate cancer was diagnosed in life among 274 of 8006 (3.6%) members of a cohort of Japanese men in Hawaii between 1965 and 1990. Only 55 (20%) of the 274 diagnosed cases died with prostate cancer, and they accounted for only 2% of the 2893 deaths that occurred among the men during this period. None of the 61 men whose tumor was found incidentally to a transurethral resection died as a result of this cancer, while it was the cause of death of 9 of 106 (8%) men with clinical cancer localized to the prostate. Forty-six of the 107 (43%) men with more extensive disease at the time of diagnosis died from prostate cancer. Step sectioning of the prostate identified prostate cancer in 80 of 293 (27%) autopsied Hawaii Japanese men who died after 50 years of age, reaching a frequency of 63% (10 of 16) among men over 80 years of age. The volume of 48 (60%) of these cancers was less than 150 mm3. These small tumors would probably not have been discovered in a screening program. Tumors larger than 1000 mm3 would probably be discovered using modern diagnostic procedures but were found in only 13 (4.4%) of the autopsied men. It is likely that a screening program to detect and treat such large, unsuspected tumors in this population would have had little impact upon the already low proportion of deaths due to prostate cancer among these Japanese men. PMID- 1306105 TI - Levels of colorectal ornithine decarboxylase activity in patients with colon cancer, a family history of nonpolyposis hereditary colorectal cancer, and adenomas. AB - Ornithine decarboxylase (ODC), a key enzyme in mammalian polyamine biosynthesis, has been proposed to be a marker of colonic epithelial cell proliferation and risk for colorectal cancer. We investigated the basal levels of ODC activity in sigmoid and rectal mucosae, and basal and tumor promoter 12-O tetradecanoylphorbol-13-acetate-induced levels of skin ODC activity in individuals with a personal history of colon cancer (n = 9 colon; n = 58 skin), a family history of nonpolyposis hereditary colorectal cancer (n = 49; n = 42), adenomas (n = 16; n = 40), and healthy, family history-negative control subjects (n = 40; n = 79). Using a fresh tissue assay and samples obtained after a standard colon lavage preparation, colon mucosal ODC levels ranged from 0 to 192 pmol/mg/h (sigmoid, 0-163 pmol/mg/h; mean, 36 +/- 32 pmol/mg/h; rectum, 0-192 pmol/mg/h; mean, 35 +/- 32 pmol/mg/h). No differences among the four groups of subjects were found for either colon or skin ODC levels, and there were no sex differences overall or in any group. These results are not compatible with the suggestion that ODC levels are a useful marker of risk for colorectal cancer. PMID- 1306106 TI - Prospective study of Lewis antigen alterations in the gastric precancerous process. AB - A prospective study with two gastric biopsies taken several years apart was carried out in 117 subjects with intestinal metaplasia who are of the Lewis(a-b+) phenotype. They are residents of a rural Andean region in Colombia displaying very high rates of gastric cancer. The anomalous expression of Lewis(a) antigens in the metaplastic epithelium carried a significantly increased risk of colonic metaplasia and dysplasia. Such risk was much higher when the simultaneous expression of sulfomucins and Lewis(a) antigen was observed. PMID- 1306107 TI - A model for the formation and removal of hemoglobin adducts. AB - Hemoglobin adducts formed by chemical carcinogens can be used as biomarkers of exposure. The kinetics of adduct formation and removal is complex and depends on the processes involved in erythrocyte removal, adduct stability, and the duration and extent of exposure. In order to relate the formation of adducts to the extent of exposure in complex exposure scenarios, a model has been developed to describe the kinetics of accumulation and removal of adducts formed in vivo. The exposure scenario, lifetime of erythrocytes, and extent of adduct formation following a single exposure are required input parameters. Predictions of adduct accumulation have been generated for a wide variety of exposure scenarios and compared with both the solutions to equations derived for adduct formation and removal and experimental observations. Loss of adduct by removal of erythrocytes from circulation, both by senescence and random removal and as a result of chemical instability, has been simulated. Equations have been derived to describe the removal of hemoglobin adducts under conditions of exposure for less than the lifetime of the erythrocyte, when removal is initially a linear function of time. This model makes possible the comparison of data obtained from different exposure scenarios and in different species. PMID- 1306108 TI - Acculturation, education, and income as determinants of cigarette smoking in New Mexico Hispanics. AB - Surveys of cigarette smoking among Hispanics in the Southwest have shown a pattern of smoking distinct from that of non-Hispanic whites, but determinants of smoking by Hispanics remain inadequately characterized. We have assessed household income, education, and language preference as predictors of cigarette smoking in 1072 Hispanic adults residing in a community in New Mexico. Cigarette smoking status (never, former, or current smoker) varied strongly with educational attainment, showing the anticipated gradient of increasing smoking as level of education declined. In contrast, cigarette smoking status did not vary in a consistent pattern with reported language preference. A composite measure of socioeconomic status, combining education and household income, predicted continued smoking among ever smokers, whereas language preference had no effect. In males, the age at which subjects started to smoke increased significantly with increasing education; a similar trend in females did not reach statistical significance. Determinants of numbers of cigarettes smoked daily were not identified. The findings suggest that, as in other U.S. populations, Hispanics in the Southwest with lower education and less income should be targeted for smoking prevention and cessation. PMID- 1306110 TI - Partial sequence and polymerase chain reaction-mediated analysis of expression of the human CYP2C18 gene. AB - We describe the isolation of the human CYP2C18 gene, a new member in the complex CYP2C subfamily, associated with the genetically-determined polymorphism for (S) mephenytoin hydroxylase. The 5' end of CYP2C18 gene was isolated from a human genomic library using a probe derived from the CYP2C10 cDNA and the 5' flanking region, exons 1 to 4 and intron-exon junctions were sequenced. With respect to intron-exon boundaries, the partial gene structure was identical to that of rat and rabbit CYP2C genes. Consensus sequences for putative 'glucocorticoid responsive elements' were observed in the 5' flanking region and in intron 1, an interesting feature in a so-called constitutively-expressed gene subfamily. The knowledge of CYP2C gene sequences is a prerequisite to genomic analysis by PCR techniques. Using oligonucleotides derived from the gene sequence, we were able to specifically detect CYP2C18 mRNAs in human liver. PMID- 1306111 TI - Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. AB - The wide variations in urinary bladder and colo-rectal cancer incidence in humans have been attributed in part to metabolic factors associated with exposure to carcinogenic aromatic and heterocyclic amines. Cytochrome P-4501A2 (CYP1A2), which catalyses N-oxidation, and acetyltransferase (NAT2) which catalyses N- and O-acetylation, both appear to be polymorphically distributed in human populations; and slow and rapid NAT2 phenotypes have been implicated as risk factors for these cancers. Caffeine has also been shown to undergo 3 demethylation by CYP1A2, and it is further acetylated to 5-acetylamino-6 formylamino-3-methyluracil (AFMU) by the polymorphic NAT2. In this report, we describe a metabolic phenotyping procedure that can be used to determine concomitantly the hepatic CYP1A2 and NAT2 phenotypes. For the NAT2 phenotype, we confirm the valid use of the urinary molar ratio of AFMU/1-methylxanthine, even in alkaline urines. For the CYP1A2 phenotype, the urinary molar ratio of [1,7 dimethylxanthine + 1,7-dimethyluric acid]/caffeine, taken at 4-5 h after caffeine ingestion, was identified from pharmacokinetic analyses of 12 subjects as being better correlated (r = 0.73; p = 0.007) with the rate constant for caffeine 3 demethylation than other previously suggested ratios. This procedure was then used to determine the CYP1A2 phenotype in subjects from Arkansas (n = 101), Italy (n = 95), and China (n = 78). Statistical and probit analyses of nonsmokers indicated that the CYP1A2 activity was not normally distributed and appeared trimodal. This trimodality allowed arbitrary designation of slow, intermediate, and rapid phenotypes, which ranged from 12-13% slow, 51-67% intermediate, and 20 37% rapid, in the different populations. A reproducibility study of 13 subjects over a 5 day or 5 week period showed that, with one exception, intraindividual variability did not alter this CYP1A2 phenotypic classification. Induction of CYP1A2 by cigarette smoking was also confirmed by the increased caffeine metabolite ratios observed in the Arkansas and Italian smokers (blonde tobacco). However, Italian smokers of black tobacco and Chinese smokers did not appear to be induced. Furthermore, probit analyses of Arkansas and Italian blonde tobacco smokers could not discriminate between phenotypes, apparently as a consequence of enzyme induction. PMID- 1306109 TI - Estimation of interhemispheric dynamics from simple unimanual reaction time to extrafoveal stimuli. AB - This essay reviews research on interhemispheric transfer time derived from simple unimanual reaction time to hemitachistoscopically presented visual stimuli. Part 1 reviews major theoretical themes including (a) the significance of the eccentricity effect on interhemispheric transfer time in the context of proposed underlying neurohistological constraints; (b) the significance of gender differences in interhemispheric transfer time and findings in dyslexics and left handers in the context of a fetal brain testosterone model; and (c) the significance of complexity effects on interhemispheric transfer time in a context of "dynamic" vs. "hard-wired" concepts of the underlying interhemispheric communication systems. Part 2 consists of a meta-analysis of 49 published behavioral experiments, in view of drawing a portrait of the best set of experimental conditions apt to produce salient, reliable, and statistically significant measures of interhemispheric transfer time, namely (a) index rather than thumb response, (b) low rather than high target luminance, (c) short rather than prolonged target display, and (d) very eccentric rather than near-foveal stimulus location. Part 3 proposes a theoretical model of interhemispheric transfer time, postulating the measurable existence of fast and slow interhemispheric channels. The proposed mechanism's evolutionary adaptive value, the neurophysiological evidence in its support, and favorable functional evidence from studies of callosotomized patients are then presented followed by proposals for critical experimental tests of the model. PMID- 1306112 TI - The ability to 4-hydroxylate debrisoquine is related to recurrence of bladder cancer. AB - Oxidative metabolism by cytochrome P450 enzymes is often involved in the activation of environmental procarcinogens. Debrisoquine, mephenytoin, and dapsone were used as in vivo probes for the activities of P4502D6, 2CMP, and 3A4, respectively, as well as dapsone for N-acetyltransferase, in order to assess the relationship between such activities and the relative risk of recurrence of bladder cancer. Urinary recovery ratios of debrisoquine and dapsone and the R/S ratio of mephenytoin were measured in an 0-8 h urine sample after simultaneous administration of debrisoquine (10 mg) and racemic mephenytoin (100 mg), and the administration of dapsone (100 mg) one week later, to patients undergoing local surgical resection of transitional cell bladder cancer of G-I, G-II, or G-III histopathology. In addition, plasma levels of dapsone and mono-acetyldapsone were determined in an 8 h plasma sample to determine the N-acetylation phenotype. Patients were followed for 3 years, to the time of tumour recurrence, or death. Three patients were lost to follow-up; of the remaining 95 patients, 55 had tumour recurrence. The debrisoquine recovery ratio was significantly greater in patients with recurrence than in individuals who remained disease-free. Among the 65 patients with non-aggressive (G-I and G-II) histopathology, two patients were lost to follow-up and 32 had tumour recurrence. In this subgroup, the debrisoquine recovery ratio was again found to be significantly greater in those individuals with tumour recurrence (p < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306113 TI - Dextromethorphan O-demethylation in a large number of French Caucasian families. PMID- 1306114 TI - The novel bilirubin/phenol UDP-glucuronosyltransferase UGT1 gene locus: implications for multiple nonhemolytic familial hyperbilirubinemia phenotypes. AB - At least three types of congenital nonhemolytic unconjugated hyperbilirubinemias, including the rare Crigler-Najjar (CN) diseases (Types I or II) and Gilbert's syndrome (affecting 6% of the population) are associated with either absent or reduced hepatic UDP-glucuronosyltransferase (transferase) activity towards the potentially toxic endogenous acceptor, bilirubin. Here, we review the biochemical studies associated with these deficiencies. Accumulated evidence from studies with an animal model of CN Type I syndrome, the Gunn strain of hyperbilirubinemic rats, suggested that multiple isozymes are absent. These confounding observations have been clarified by a flurry of reports which have revealed the molecular basis for the complex disease phenotype in the Gunn rat and by the isolation and description of a novel human gene complex, UGT1, which encodes multiple and independently-regulated transferase isozymes that contain identical carboxyl terminal regions (246 amino acids). Finally, we discuss the implications of the gene organization and genetic defects determined for four different CN Type I individuals as a basis for a model which explains the inheritance pattern and genotypes of other familial unconjugated hyperbilirubinemias. PMID- 1306115 TI - Molecular genetics of human aldehyde dehydrogenase. AB - Four non-allelic genes, which encode four different aldehyde dehydrogenase (ALDH) isozymes, have been cloned and characterized at the present time. The coding nucleotide sequences, and organization of introns and exons of these genes have been elucidated. The ALDH1 gene encodes the major cytosolic ALDH1 existing in the liver and other tissues. The genetic deficiency of this isozyme was found at a low frequency (<< 10%) in both Caucasians and Orientals. The deficiency and alcohol sensitivity character are inherited together in one large Caucasian family examined. The ALDH1 gene contains two hormone response elements in its upstream 5' region. The ALDH2 gene encodes the major liver mitochondrial ALDH2 which has a very low Km for acetaldehyde. The atypical ALDH2(2) allele is common (about 30%) in Orientals; and subjects with ALDH2(2) allele, both homozygous and heterozygous status, lack ALDH activity. These individuals are alcohol sensitive and have a markedly reduced risk in developing alcoholism and alcoholic liver diseases. The ALDH3 gene produces a cytosolic ALDH3 isozyme existing in the stomach and liver carcinoma but hardly in normal liver. The ALDH3 locus is polymorphic in Orientals and presumably other populations. The ALDH5 gene, which is expressed in testes and liver, is highly polymorphic in both Caucasians and Orientals. The variation of these two loci may affect the development of alcohol related problems. PMID- 1306116 TI - Human liver thiopurine methyltransferase pharmacogenetics: biochemical properties, liver-erythrocyte correlation and presence of isozymes. AB - Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP). TPMT activity in the human red blood cell (RBC) is controlled by a common genetic polymorphism. Gene frequencies for this polymorphism are such that approximately one in 300 subjects is homozygous for the allele for low activity and lacks RBC TPMT activity, 11% of subjects are heterozygous and have intermediate levels of enzyme activity and 89% are homozygous for the allele for high activity. Our experiments were performed to determine whether the properties of TPMT in an important human drug metabolizing organ, the liver, were similar to those of RBC TPMT and to test the hypothesis that the genetic polymorphism which controls TPMT activity in the human RBC might also regulate the level of this enzyme activity in hepatic tissue. Human liver TPMT is a cytoplasmic enzyme and the Km values for 6-MP and S-adenosyl-L methionine, cosubstrates for the reaction, were 580 microM and 2.7 microM, respectively. These properties, as well as the sensitivity of human liver TPMT to a panel of methyltransferase inhibitors, were similar to those of RBC TPMT. The enzyme activity was then measured in 119 surgical biopsy samples of hepatic tissue. Average hepatic TPMT activity was 13.6% higher in samples from male than in those from female patients. Frequency distribution histograms demonstrated the presence of a subgroup with intermediate enzyme activity that included 8.4% of samples. In addition, when TPMT activity was measured in both RBCs and hepatic tissue for 35 patients, those with inherited intermediate levels of RBC TPMT activity also had intermediate hepatic enzyme activity. Finally, ion exchange chromatography demonstrated the presence of two isozymes of TPMT in human hepatic tissue, but the isozymes did not appear to explain the molecular mechanism responsible for the genetic polymorphism. These results were compatible with the conclusion that the genetic polymorphism which controls TPMT activity in the RBC also controls levels of this important enzyme activity in a major human drug metabolizing organ, the liver. PMID- 1306117 TI - Induction of various cytochromes CYP2B, CYP2C and CYP3A by phenobarbitone in non human primates. AB - Male and female patas (Erythrocebus patas) and cynomolgus (Macaca fascicularis) monkeys were treated with phenobarbitone (PB) and examined for the induction of various cytochrome P450 (P450)-mediated drug metabolizing enzymes. Hydroxylation of testosterone at the 6 beta, 2 beta, and 15 beta positions, metabolites normally associated with CYP3A P450s increased 2- to 5-fold in PB-treated animals. Induction of this P450 family was confirmed by the use of polyclonal antisera directed against the human CYP3A enzymes which inhibited both induced and constitutive 6 beta- and 15 beta-hydroxylase activities in both species of monkeys. The enzymatic activities testosterone 16 beta-hydroxylation, pentoxyresorufin O-dealkylation [PROD], and benzyloxyresorufin O-dealkylation [BZROD] typically associated with the rodent CYP2B subfamily in rodents were also examined. Testosterone 16 beta-hydroxylation activity was highly induced up to 15 fold in both species of monkeys to maximal levels similar to those induced in PB treated male rats. BZROD was similarly induced up to 10-fold in both species of monkeys, but the maximal levels of BZROD achieved were substantially lower than those obtained in PB-treated rats. Finally, PROD yielded an idiosyncratic response showing substantial induction (> 30-fold) in certain patas monkeys (4 out of 8) but minimal (< 5-fold) induction in the other patas monkeys (4 out of 8) or any of the cynomolgus monkeys (0 out of 8). Immunodetection of various cytochromes using polyclonal antisera directed against rat cytochromes confirmed the induction of CYP3A proteins as well as the induction of protein(s) immunologically cross-reactive with rat CYP2B P450s. BZROD, PROD, or testosterone 16 beta-hydroxylase activities, were not inhibited by antibody to CYP3A P450s. However, high concentrations of polyclonal antiserum directed against rat CYP2B inhibited all three activities in PB-induced patas monkeys. In contrast, this antiserum failed to inhibit the hydroxylation of testosterone at the 6 beta or 2 beta positions. Induction of the CYP2C subfamily was observed by immunochemical detection. Interestingly, induction of this subfamily appeared to be more pronounced in cynomolgus than in patas monkeys. Finally, we failed to observe significant sex-dependent differences in P450-mediated enzymatic activities in either control or induced monkeys. These results confirm the induction of a similar spectrum of P450 proteins by PB in non-human primates to that which has previously been observed in rodents. PMID- 1306118 TI - Caffeine as a probe for human cytochromes P450: validation using cDNA-expression, immunoinhibition and microsomal kinetic and inhibitor techniques. AB - The molecular basis for the use of caffeine (CA; 1,3,7-trimethylxanthine) as a probe for specific human cytochromes P450 has been investigated. The CA 1-, 3- and 7-demethylations (to form theobromine, paraxanthine and theophylline, respectively) all followed biphasic kinetics in human liver microsomes. Mean apparent Km values for the high- and low-affinity components of the demethylations ranged from 0.13-0.31 nM and 19.2-30.0 mM, respectively. cDNA expressed CYP1A2 catalysed all three CA demethylations, and the apparent Km for CA 3-demethylation (the major metabolic pathway in humans) by the expressed enzyme was similar to the Km for the high-affinity liver microsomal CA 3 demethylase. IC50 values for inhibition of the CA demethylations by alpha naphthoflavone were similar for both expressed CYP1A2 and the high-affinity microsomal demethylases. Moreover, CA was a competitive inhibitor of expressed CYP1A2 catalysed phenacetin O-deethylation, with the apparent Ki (0.080 mM) closely matching the apparent Km (0.082 mM) for CA 3-demethylation by the expressed enzyme. Expressed CYP1A1 was additionally shown to catalyse the 3 demethylation of CA, although activity was lower than that observed for CYP1A2. While these data indicate that CYP1A2 is responsible for the high-affinity component of human liver CA 3-demethylation, two limitations associated with the use of CA as an in vitro probe for CYP1A2 activity have been identified: (i) CA 3 demethylation reflects hepatic CYP1A2 activity only at appropriately low substrate concentrations; and (ii) CA is a non-specific CYP1A substrate and CYP1A1 may therefore contribute to CA 3-demethylase activity in tissues in which it is expressed. An anti-CYP3A antibody essentially abolished the 8-hydroxylation of CA to form trimethyluric acid, suggesting formation of this metabolite may potentially serve as a marker of CYP3A isozyme(s) activity. PMID- 1306119 TI - Metabolic, molecular genetic and toxicological aspects of the acetylation polymorphism in inbred mice. AB - Over the past 10 years, much fascinating information has been obtained concerning the biochemistry, genetics, toxicological implications and molecular genetics of the N-acetylation polymorphism in mice. Using C57BL/6J (B6) mice as representative of rapid acetylation and A/J (A) mice as representing slow acetylation, it has been shown that the polymorphism observed in N acetyltransferase (NAT) activity in liver also occurs in kidney, bladder, blood, and other tissues. The development of congenic acetylator mouse lines derived from B6 and A, have provided the necessary tools to study the role of the acetylation polymorphism, on either the B6 or A genetic background, free of nearly all other genetic differences between these strains. Eliminating genes which modify and complicate the differences due to the acetylator genes make the congenic lines very useful in toxicology studies, particularly those involving carcinogenesis. The molecular genetic basis of the acetylator polymorphism in B6 and A mice involves two Nat genes. Nat-1 encodes a protein termed NAT1 which is identical in rapid and slow acetylator strains. Nat-2, however, differs between rapid and slow strains by a single nucleotide change in the coding region. The corresponding NAT2 proteins differ by a single change at amino acid 99: an hydrophilic asparagine in rapid acetylator NAT2 to an hydrophobic isoleucine in NAT2 from slow acetylators. The mechanistic basis for the differences between rapid and slow acetylation in mice appears to be that NAT2 from the rapid B6 strain is 15-fold more stable at 37 degrees C and is transcribed/translated with a maximal efficiency twice that of the enzyme from slow acetylator A mice. Results discussed in this review indicate that mice provide an excellent system for studying the N-acetyltransferase polymorphism and also are useful for modelling several aspects of the human N-acetyltransferase polymorphism. PMID- 1306120 TI - Guinea pig or rabbit lung flavin-containing monooxygenases with distinct mobilities in SDS-PAGE are allelic variants that differ at only two positions. AB - Both guinea pig and rabbit express two variants of the 'lung' flavin-containing monooxygenase (FMO), observed as three distinct phenotypes based on mobility differences in SDS-PAGE. Samples of messenger RNA prepared from lungs of the two homozygous phenotypes of the guinea pig were used for the construction of two cDNA libraries. The libraries were screened with a cDNA encoding the rabbit lung FMO, and positive clones for each guinea pig lung FMO variant were isolated and sequenced. A full length clone from each library was found to encode a protein of 535 amino acids containing two pyrophosphate binding sites. Comparison of the sequences of the guinea pig and rabbit lung FMOs shows that their primary structures are 86% identical. The coding region sequences of the guinea pig variants differ at only two positions, and both differences result in amino acid substitutions. Sequence analysis has also been completed on a partially characterized variant of the rabbit lung FMO. As with the guinea pig, the nucleotide and amino acid sequences of the rabbit variants differ at only two positions. The cDNAs encoding the guinea pig variants were expressed in yeast. The activities of the enzymes are characteristic of the lung FMO, and the mobilities of the expressed enzymes are the same as those observed for the variants present in guinea pig pulmonary microsomal preparations. Similar to findings for the rabbit, analysis of genomic DNA indicates that the guinea pig lung FMO is associated with a single gene. The results of cDNA sequence analysis, expression in yeast, and analysis of genomic DNA indicate that the multiple lung FMOs in guinea pig and rabbit are allelic variants whose mobilities in SDS-PAGE are markedly altered by minimal changes in primary structure. PMID- 1306121 TI - Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants. AB - Arylamine N-acetyltransferase catalyses the N-acetylation of primary arylamine and hydrazine drugs and chemicals. N-acetylation is subject to a polymorphism and humans can be categorized as either fast or slow acetylators according to their ability to N-acetylate polymorphic substrates in vivo. Previously, slow acetylation has been linked to four distinct polymorphic N-acetyltransferase (pnat) alleles each of which contains one or more point mutations within the coding region of the pnat gene. One new rare slow variant of pnat has been identified by cloning and sequencing the pnat DNA from an individual whose NAT phenotype was determined by in vivo acetylation of the polymorphic substrate sulphamethazine. This allele, designated S1c, differs from the wild type fast allele at nucleotide positions 341 and 803. A second new rare slow allotypic variant, designated S3, has been identified by resistance of the pnat specific DNA to digestion with the restriction enzymes Fok I and Bam HI. A method of genotyping individuals for the arylamine N-acetyltransferase (NAT) polymorphism is presented which correctly predicts the phenotype of greater than 95% (21 of 22) of individuals as measured by the extent of acetylation of sulphamethazine in urine. This refined genotyping method was applied to a clinical population of 48 Caucasians with classical or definite rheumatoid arthritis each receiving daily between 150 and 500 mg of the anti-rheumatic drug, D-penicillamine. There is no difference in the N-acetyltransferase phenotype of the individuals who developed proteinuria and the control group with no adverse effects. PMID- 1306122 TI - Interindividual variability of coumarin 7-hydroxylation in healthy volunteers. AB - A test designed to estimate the extent and rate of formation of 7-hydroxycoumarin by measuring the urinary excretion of the metabolite in humans after administering 5 mg coumarin was developed. Coumarin was rapidly metabolized after oral administration and more than 95% of the 7OHC formed was excreted in 4 h. The total amount of 7OHC formed was 64 +/- 15% (mean +/- SD, variation 20-100%) of the dose given. The percentage of 7OHC excreted in 2 h, as compared with the 7OHC excretion in 4 h, was found to be a constant and stable individual characteristic for the rate of the formation of 7OHC ('2 h coumarin test'). In 110 volunteers, there was a great interindividual variability in the extent and rate of 7OHC formation. Four individuals had relatively 'slow' coumarin test values (50-60%), but much larger populations would be needed for the demonstration of polymorphism. PMID- 1306123 TI - Structural basis of the butyrylcholinesterase H-variant segregating in two Danish families. AB - The rare H-variant of human butyrylcholinesterase is a quantitative variant that reduces serum butyrylcholinesterase activity by about 90%. Individuals who are heterozygous for both the H-variant and the atypical variant are abnormally sensitive to the muscle relaxant succinylcholine. By using standard phenotypic serum assays, the Danish Cholinesterase Research Unit identified four individuals from two unrelated pedigrees who were heterozygous for both the H-variant (H) and the atypical (A) variant. DNA of these A/H individuals was extracted from white blood cells. Using the polymerase chain reaction and subsequent DNA sequencing, a point mutation was found at nucleotide 424 which changed amino acid 142 from valine to methionine. The previously identified atypical mutation, Asp 70 to Gly, was also seen, which segregated apart from the H-variant mutation in family studies. These two mutations were found in all four A/H individuals. PMID- 1306124 TI - A methodological investigation on the estimation of the S-mephenytoin hydroxylation phenotype using the urinary S/R ratio. AB - After a single oral dose of racemic mephenytoin the S/R ratio in urine can be used to phenotype extensive (EM) and poor metabolizers (PM) of S-mephenytoin. We confirmed the increased S/R ratio by storage time in EM because of the hydrolysis of a conjugate of S-mephenytoin excreted in EM, but not in PM. The S/R ratio in the 0-8 h urine increased 8- to 127-fold (from 0.22 +/- 0.16 to 9.9 +/- 11.3) after acid treatment of urine from 30 EM, but there was no effect of acid in that of 12 PM. We suggest that the phenotype of mephenytoin in combination with debrisoquine can be determined in the 0-8 h urine by estimating the mephenytoin S/R ratio before and after acid treatment. PMID- 1306125 TI - The pharmacogenetics of chemical carcinogenesis. AB - The human body is endowed with a large number of xenobiotic chemical metabolizing enzymes, a significant proportion of which are polymorphic and thus render one individual at greater or lesser risk than another of chemically-induced disease. All examples of genetic polymorphism of chemical metabolizing enzymes have been reviewed in relation to their potential to activate and detoxicate procarcinogens and promutagens. Many examples are cited whereby phenotype can act as a carcinogenic risk factor. With the availability of a large amount of DNA sequence data for chemical metabolizing enzymes there has emerged a number of polymerase chain reaction (PCR) strategies aimed at discerning one metabolic phenotype or another. This is seen as a very positive and democratic scientific development, widening the franchise for studies of disease risk. Nevertheless, it is argued that, at these early stages with many laboratory-based scientists scarcely familiar with epidemiological study design, a cautious approach should obtain when interpreting single studies. PMID- 1306126 TI - Metabolic cytochrome P450 genotypes and assessment of individual susceptibility to lung cancer. AB - Three polymorphic cytochrome P450 genes that have attracted interest for their potential role in human pulmonary carcinogenesis, i.e. CYP1A1, CYP2D6 and CYP2E1, were studied in a population consisting of 106 lung cancer patients and 122 healthy controls. Polymorphism of the CYP2D6 gene encoding for debrisoquine hydroxylase was determined using XbaI restriction fragment length polymorphism (RFLP) analysis together with a PCR based method. All of the three most common presently known defective alleles of CYP2D6 were detected by this application. Subjects having genotypes either homozygous or heterozygous for the CYP2D6 wild type alleles were classified as extensive metabolizers (EMs) of debrisoquine whereas poor metabolizers (PMs) had two defective alleles. The PM individuals are thought to be less prone to develop lung cancer. The CYP1A1 and CYP2E1 genes were studied by RFLP analyses using Msp I and Dra I restriction enzymes, respectively, giving rise to two different sized hybridizable fragments in Southern blot analyses. In these RFPL analyses genotypes homozygous to the mutated allele have been presented as potent determinants of individual lung cancer risk. In the present study no association between polymorphic CYP1A1 and CYP2E1 genotypes and susceptibility to lung cancer was found. However, CYP2D6 polymorphism studies of the 122 healthy controls revealed seven poor metabolizer genotypes (5.7%), which compares well with the previously observed phenotypic distribution in the Finnish population, whereas only one PM genotype (1/106) was found among the lung cancer patients. These results agree with the previous suggestions that PMs of debrisoquine are less susceptible to lung cancer than EMs. PMID- 1306127 TI - Genetic polymorphism of cytochromes P450: interethnic differences and relationship to incidence of lung cancer. AB - The cytochromes P450 participate in the metabolic activation of precarcinogens. Recent results reveal that many P450 genes are polymorphically distributed. Different investigators have tried to link polymorphic variants of the CYP1A1, CYP2D6 and CYP2E1 genes to the incidence of cancer, particularly lung cancer, in Asian and Caucasian populations. In the current overview we briefly summarize this research. It appears that interesting functionally linked interindividual differences in the CYP1A1 gene have been found and could be of importance in understanding differences in susceptibility to lung cancer. On the other hand, the data presented regarding CYP2D6 and CYP2E1 are less promising. We also describe interethnic differences in the P450 gene structures as a major obstacle for extrapolation of results between different ethnic groups. PMID- 1306128 TI - Epidemiology and pathophysiology of ethanol-associated gastrointestinal cancer. AB - Various epidemiological studies have given evidence on the correlation between alcohol intake and different types of cancer, especially in the upper alimentary and respiratory tract and in the liver. This review discusses the tumour stimulating effects of ethanol associated mechanisms. PMID- 1306129 TI - Sources of genotoxicity and cancer risk in ambient air. AB - Products of incomplete combustion are identified as a major source of carcinogenic risk in urban areas, especially those from small non-industrial sources. The major ubiquitous emission sources outdoors in populated areas are residential home heating and motor vehicles. Indoors the major combustion source is environmental tobacco smoke. Polycyclic organic matter adsorbed onto the particles emitted from incomplete combustion are estimated to make the largest contribution to human genotoxic and cancer risk. Mutagenic emission factors combined with dispersion modelling indicated that automobiles and heating sources were major sources of mutagens. Ambient air studies to apportion the sources of mutagens in non-industrial areas confirmed this prediction. To apportion and estimate the cancer risk of ambient organic matter from particles in vivo animal tumour data, receptor modelling and human exposure data were combined. Tumourigenicity studies of the source apportioned ambient organic matter provided the relative tumour potencies of two ambient samples of different source composition. The human cancer unit risks were developed based on the comparative potency method using tumour data from these ambient samples. Residential wood combustion accounted for 75% of the exposure to particle associated organics, but only 20% of the estimated cancer risk. The remaining 80% of the risk appears to be associated with the mobile source component and atmospheric transformation products from these source emissions. PMID- 1306130 TI - Risk assessment of urban air pollution. AB - Urban air pollution, originating in western countries mainly from automotive engine exhausts, contains thousands of components, many of which are genotoxic, i.e. are putative cancer initiators. Other pollution components, such as NO2 and certain particles, may have cocarcinogenic/promotive effects, at least at higher exposure levels. Cancer risk assessment of this complex mixture has to combine data from the exposure history, from epidemiological studies as well as from animal carcinogenicity tests, and from in vitro studies of fractions and individual components. Data for metabolism and pharmaco-kinetics have also to be considered. A multiplicative linear model is assumed to be valid for cancer initiation at low levels. Attempts are being made to determine the target dose from ultimate carcinogens (reactive metabolites) via macromolecule adduct levels, and to base the risk assessment on the radiation-dose equivalent to the chemical dose. So far this has been possible only for simple alkenes, which are metabolized to epoxides, and indirectly, via benzo(a)pyrene (BaP), for particle bound polycyclic aromatic hydrocarbons (PAH). The lifetime risk of cancer (all sites) from ethene is estimated accordingly to 1.4 x 10(-4) per microgram m-3, and from PAH to 12 x 10(-4) per ng m-3 BaP. For other components indicated to give risk contribution (NOx, volatile PAH, benzene, aldehydes, butadiene) essential data are lacking and only very rough estimates can be given at this time. PMID- 1306131 TI - Assessment of PAH-exposure among coke oven workers. AB - Coke oven workers are exposed to high concentrations of polycyclic aromatic hydrocarbons. Only recently have methods been developed to try to assess the individual, biologically significant exposure. The only coke oven plant in Finland started to function in 1987, in Raahe, enabling the implementation of a cohort study among the workers to determine the usefulness of some currently available biomonitoring methods, e.g. methods of measuring PAH-DNA adducts. Urine and blood samples were taken several times from a sample of workers starting from before they worked at the plant. A questionnaire (smoking, diet, former and current occupations) was filled in by the workers at every sampling, and air samples (personal and stationary) were collected at the same time. The mean values of both benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were measured by synchronous fluorescence spectrophotometry (SFS) and the antibodies to these adducts increased somewhat after the work at the plant started. However, all the adduct values were low, and no differences between the smokers and non-smokers at any time point were detected. Battery workers had slightly increased means of BPDE-DNA adducts compared to non-battery workers. Also, coke oven workers had slightly higher adduct values than age, sex and smoking matched controls. PMID- 1306132 TI - Genetic changes in breast carcinomas in an Icelandic population. AB - We have examined breast tumour samples from 109 unselected breast cancer patients for genetic changes on chromosomes 13 and 17. We have looked for allelic losses, firstly, at the retinoblastoma locus, RB1, on chromosome 13q, and secondly, on both arms of chromosome 17. We have also studied the same samples for amplification of the erbB2 oncogene. We searched for mutations in four well conserved areas of the p53 gene using constant denaturant gradient electrophoresis (CDGE). Allelic loss or rearrangement was detected in a large proportion of the tumours, affecting 37-51% of cases with different probes. The areas most frequently affected were 17p13.1 and 17p13.3. Point mutations and small deletions in the p53 gene on 17p13.1 were detected in 16% of the tumours. The data on genetic changes were then analyzed for three different correlations: 1) co-operation between different lesions, 2) association with family history of breast cancer, 3) correlation with clinical factors and prognosis. There was association between losses at the retinoblastoma locus and losses on 17p and 17q. We also found an association between p53 mutations and amplification of the erbB2 oncogene. Relatives of patients having deletions at the retinoblastoma locus and/or sites on chromosome 17 in the tumours have a significantly increased relative risk of developing breast cancer. No such correlation is found for p53 mutations or erbB2 amplification. No p53 germline mutations were detected. P53 mutations do, however, appear to be a strong indication of poor prognosis in this population. PMID- 1306133 TI - Detection of DNA variation in cancer. AB - Detection of DNA variation in cancer is central to the identification of relevant genes and mutations involved in the tumourigenic process. Diverse methods exist for such detection. One category of methods is for the detection of frequent sites for larger DNA alterations in cancer. Such areas may provide clues to the positioning of relevant genes, such as loss of heterozygosity (LOH) as in the case of tumour suppressor genes. Another category of methods is for the detection of single base mutations within specific genes. Frequently, such mutations may obliterate normal protein function. Among the most well-known are DGGE, SSCP, the HOT-method and direct sequencing. The methods for detection of DNA variation of these different levels are discussed. Two methods are presented in more detail. At the large-scale level, two-dimensional DNA fingerprinting has the potential of revealing the extent and location of altered DNA regions. This method is demonstrated using a panel of breast cancer patients. As an example of methods for the small-scale level, a recent development from DGGE, constant denaturant gel electrophoresis (CDGE) is demonstrated. This method has successfully been applied for the detection of mutations in a number of genes. Results with this method in studies of the RB1 gene are given, and its applicability as a screening tool for base mutations is discussed. PMID- 1306134 TI - Missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus. AB - Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens. PMID- 1306135 TI - Approaches to the prediction of human cancer risk. AB - Epidemiological studies provide the only direct means of measuring the risk of cancer in humans and for investigating effects directly avoiding interspecies extrapolation. Epidemiology is, however, too insensitive to detect small increases in risk. Furthermore, traditional epidemiology cannot be used prospectively to indicate future problems nor to explore the current exposure situation. Ideally, cancer hazards should be identified before humans are exposed. For the foreseeable future, therefore, identification of carcinogens will necessarily depend heavily on data derived from studies in experimental animals. Emerging molecular biological techniques, if used critically, hold great promise for resolving many contemporary puzzles in cancer risk prediction. PMID- 1306136 TI - Evolutionary aspects of human cancer. AB - Evolutionary aspects of human cancer can be dealt with at two levels--on the one hand long-term evolution involving hereditary effects between generations; and on the other hand evolutionary processes operating within the organisms between tissues, cells and cell constituents, which also comprise genetic alterations, selection and adaptation. These two levels of evolution can be designated as phylogenetic and ontogenetic evolution, respectively. Concerning phylogenetic evolution there must have been a strong selection against neoplastic diseases occurring at reproductive age and a variety of protective mechanisms against carcinogenic agents have been developed. Cancer is therefore primarily a disease of old age, which does not constitute a significant risk in natural populations for the simple reason that the life length is too short. The development of an individual comprises selection forces between cells and tissues, which are particularly striking for the multistage development of tumours. The accumulation of several genetic alterations in the same cells, as illustrated by the analysis of colorectal tumours, must require a pronounced clonal expansion between each event. Such selective growth effect has recently been demonstrated for the tumour suppressor gene p53 in brain tumours. Cancer often implies a break down of between balanced systems antagonistic forces, such as oncogenes and suppressors of oncogenes. Examples of this are provided by the genetic regulation of metastasis, involving metalloproteinase as well as the inhibitor of metalloproteinase. The immortalization of cells by transformation points to the fact that programmed cell death and the balance between suicide genes and suppressors of such suicide genes is affected. PMID- 1306137 TI - [Bronchoesophageal fistulae: apropos a case rarely seen]. AB - One case of acquired oesophago-bronchial fistula is reported. Diagnostic images are presented. Pathogenesis, clinical and therapeutics features are discussed. PMID- 1306138 TI - [The surgery of liver trauma (clinical contribution)]. AB - Authors perform a retrospective review of all hepatic injuries operated on between 1974 and 1990 at Clinica Chirurgica II (ex Patologia Chirurgica II, ex Semeiotica Chirurgica) of Policlinico San Matteo (IRCCS) of Pavia. Thirteen patients were treated, 9 men and 4 women, with age ranged from 13 to 68 years and a mean age of 38 years. They were 21% of all patients operated on for abdominal trauma. Penetrating wounds were present in only two cases (15%), the other patients (85%) were affected by blunt trauma. The mechanisms of injuries were: road accidents (77%), fall at work (8%), gun shot wound (8%), stab wound (8%). All patients had associated injuries. The mortality was 31%: one patient died for haemorrhagic shock and the other three for craniocerebral injuries. After reviewing the several haemostatic techniques advocated for the various types of hepatic injuries, the authors stress that, although most lesions are minor and can be managed by simple technique of haemostasis, often the prognosis is severe for the associated injuries. PMID- 1306139 TI - [A rare complication due to diverticulitis]. AB - The AA. report about a case of hepatic abscess found in a operated patient for perforation of a sigmoid diverticulum. The AA. made some consideration on the rarity of the hepatic abscess as complication of diverticulum perforation. PMID- 1306140 TI - [The complications of lumbotomies]. AB - After having described the surgical anatomy of the lumbar region, with particular regard to the relationships with pleura and peritoneum, as well as to the course of the nervous structures of the region (12th intercostal, ileohypogastric and ileoinguinal), the authors describe the possible complications related with the surgical approaches to the lumbar region. Pathogenesis of post-operatory pains and parietal hypotonies is especially evaluated; these complications may be caused by section, ligature or compression of one or more nervous trunks. The authors conclude that the respect of the anatomic structures located in the lumbar region represents the best way in order to prevent most complications related to lumbotomies. PMID- 1306141 TI - [Obturator hernia]. AB - Obturator hernia, which is a rare cause of intestinal occlusion, generally presents non-specific signs and symptoms. Radiology may be sometimes useful for the diagnosis. Four cases of obturator hernia are described, and the possible surgical access routes are illustrated, emphasizing the use of prosthetic mesh. PMID- 1306142 TI - [Splenic arteriovenous fistula (a clinical case)]. AB - A splenic arteriovenous fistula is a situation often presenting with signs of portal hypertension and with a characteristic murmur. Though rare, the possibility of a splenic arteriovenous fistula must be borne in mind in differential diagnosis, since it can be corrected surgically by resolving the portal hypertension. PMID- 1306143 TI - [Surgery and chemotherapy in the treatment of primary gastric lymphomas: case review]. AB - Fifty-seven patients with primary gastric non-Hodgkin's lymphoma are here reported. All our patients were treated with surgery as first step procedure. Thirty-six were treated in addition with chemotherapy (four of them with radiotherapy also). Thirty-eight were stage IE and nineteen IIE. According to the Working Formulation, 12 cases were classified as low, 25 intermediate and 20 high malignancy. 55 patients achieved a complete remission (96%) and only 6 relapsed (11%). The 10-year disease-related survival is 89%. Patients treated with combined surgery and chemotherapy were mainly a high risk group (high grade histologic subtype, stage IIE, incomplete resection). Nevertheless the survival of this group was similar to the group initially treated with surgery alone (p = 0.17) in which such unfavorable prognostic factors were not present. Stage, presence of residual tumor after surgery, sex and age did not statistically correlate with survival. Furthermore, there was not statistical difference among the various histological subgroups (p = 0.16). We stress the importance of cooperation among surgeons and oncologists in order to plan an appropriate treatment. PMID- 1306144 TI - [Anastomotic complications in the surgical treatment of rectal neoplasms]. AB - The authors review the problems relating to the healing of colorectal anastomotic complications following anterior resection. They report on their own experience with 328 anastomoses, 281 of which constructed manually and 47 using a mechanical suturing gun. Following manual anastomosis, the reported incidence of clinical dehiscence was 1%, as against a 10.3% incidence of radiologically detectable dehiscence. In the cases of mechanically produced anastomoses the incidence of clinical dehiscence was 6.4%. In 2 cases stenosis developed as a result of the clinically manifest dehiscence following manual anastomosis. In the patients undergoing mechanical anastomosis, occlusion occurred in one case and stenosis in another, without any concomitant peri-anastomotic inflammatory processes; these complications were caused by a membrane extending between the margins of the anastomosis. The authors ascribe the greater incidence of clinically important dehiscence following mechanical anastomosis to a greater sensitivity of the mechanical suture to colonic contamination compared to the manual suture. According to the authors, the stenosis is attributable to inflammatory processes resulting from the dehiscence in the manual anastomosis cases and from the anastomotic structure in the mechanical-suture case. PMID- 1306146 TI - The influence on pregnancy of anti-SSA/Ro antibodies in systemic lupus erythematosus. AB - Excessive fetal morbidity and mortality have been noted in patients with systemic lupus erythematosus (SLE). The influence of anti-SSA/Ro antibodies on fetal outcome in SLE patients has rarely been reported, but its high association with congenital heart block or neonatal lupus syndrome is well known. In 430 pregnancies of the 154 SLE patients studied, there was an increased frequency of adverse fetal outcome compared with controls. There was no significant difference in the rates of adverse fetal outcome between anti-SSA/Ro positive and negative SLE patients, except that the incidence of intrauterine growth retardation increased in the positive patients. However, pregnant SLE patients with high titer of anti-SSA/Ro antibodies had more adverse fetal outcomes. All three infants who suffered congenital heart block/neonatal lupus syndrome were associated with maternal anti-SSA/Ro antibodies. The frequency of congenital heart block/neonatal lupus syndrome was 0.79% (3/379) in livebirths of all SLE patients and 1.17% (3/257) in live-births by anti-SSA/Ro positive SLE mothers. PMID- 1306145 TI - Suppression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and granulocyte-monocyte colony stimulating factor secretion from human monocytes by an extract of Poria cocos. AB - Fu-Ling, the sclederma of Poria cocos (Schw.) Wolf, has long been used as a sedative and diuretic. However, data in this report suggest that Fu-Ling is a potential suppressor of cytokine secretion from human peripheral blood monocytes under in vitro condition. Monocyte culture medium containing 10% of Fu-Ling extract significantly inhibited secretion of TNF-alpha, IL-beta, IL-6 and GM-CSF from the monocyte monolayer. However, as Fu-Ling extract content was gradually reduced, cytokine secretion was augmented in comparison with the cytokine secretion in drug-free controls. This augmentative effect resulted from the trace amount (1.24 ng/ml in 0.62% of Fu-Ling extract) of lipopolysaccharide (LPS) which contaminated the Fu-Ling extract during the preparation process, since TNF-alpha, IL-1 beta and IL-6 secretion induced by 0.62% Fu-Ling extract could be significantly inhibited by polymyxin B, an LPS inhibitor. Furthermore, the amounts of TNF-alpha IL-1 beta and IL-6 induced by 1 ng/ml of LPS without the presence of drug were more than that induced by 0.62% of Fu-Ling extract. Thus, cytokine secretion induced by LPS contamination (1.24 ng/ml) in the Fu-Ling extract was partially suppressed by 0.62% of the Fu-Ling extract itself. GM-CSF secretion in the medium containing 0.62% of Fu-Ling extract was not induced by LPS since: a) GM-CSF induced by 0.62% Fu-Ling extract could not be inhibited by polymyxin B; b) LPS at 1 ng/ml showed no activity indicating induction of GM-CSF secretion. PMID- 1306147 TI - Exclusion probabilities of red cell antigen systems for Chinese. AB - Little data are available in the literature for Chinese people, regarding genotype frequencies of red cell antigen systems. Furthermore, no recommendations for proper selection of red cell antigen systems for paternity testing have been established for a Chinese population. Consequently, calculating a paternity index is impossible. Blood typing of 336-1919 samples of Taiwanese Chinese was undertaken to determine various red blood cell antigens. Gene frequencies and probabilities of exclusion (PE) for the red cell antigen systems were then analyzed. The distributions of the red cell antigens were quite homogeneous. The incidence of D, s, k, Fya and Lub antigens was high, 99.6%, 99.7%, 100%, 99.8% and 99.4%, respectively. On the contrary, that for the K antigen was very low. The PE for the ABO, Rh, MNSs, Kell, Duffy, Kidd, P, and Lutheran systems was 0.1910, 0.1961, 0.2237, 0.0003, 0.0444, 0.1870, 0.0806, and 0, respectively. The cumulative PE (CPE) using ABO, Rh, MNSs, Kell, Duffy, Kidd, P and Lutheran systems was 0.6394, while CPE for ABO, Rh, MNSs, Duffy, Kidd, and P systems was 0.6394. Thus, it appears that the Kell and Lutheran systems are not suitable for paternity testing because of their low probability of exclusions. Duffy system may also be excluded for its low PE. The CPE for ABO, Rh, MNSs, Kidd and P systems was 0.6226. PMID- 1306148 TI - Anti-Jo-1 antibody in patients with polymyositis/dermatomyositis. AB - Interstitial lung disease (ILD) has been recognized as a manifestation of polymyositis or dermatomyositis (PM/DM). Patients with PM/DM with anti-Jo-1 antibody had a higher incidence of ILD. Thirty-five patients with PM/DM were studied the antibodies. Six (16.1%) were found to have them. ILD occurred in all 6 anti-Jo-1 positive patients, as opposed to 10 (34.5%) of 29 anti-Jo-1 negative patients. Only 2 cases of undifferentiated connective tissue disease among 1320 patients with various kinds of collagen vascular diseases other than PM/DM were positive for anti-Jo-1 antibody. These two patients also had lung involvement. Among six PM/DM patients with anti-Jo-1 antibody, dyspnea preceded proximal muscle weakness in three patients. In one case, the anti-Jo-1 antibody had been detected one month prior to the onset of myositis. Anti-Jo-1 antibody is a useful marker for PM/DM with ILD. PMID- 1306149 TI - The phenotype and gene frequencies of human platelet specific antigens among Chinese in Taiwan. AB - Human platelet specific antigens (HPA) were serologically typed among 48 to 567 samples of blood from Chinese in Taiwan by using the mixed passive hemag glutination method (MPHA). The prevalence found was: HPA-la (P1A1), > 99.9% (48/48); HPA-2b (Koa or Siba), 9.0% (51/567); HPA-3a (Baka), 84.8% (481/567); HPA 4a (Yukb), > 99.9% (567/567); HPA-4b (Yuka), 0.5% (3/567); HPA-5b (Br(a)), 32.6% (185/567); and Nak(a), 98.4% (558/567). The gene frequencies for these antigens were: HPA-la (P1A1), > 0.999; HPA-2b (Koa or Siba), 0.046; HPA-3a (Bak(a)), 0.611; HPA-4a (Yukb), 0.997; HPA-4b (Yuka), 0.003; HPA-5b (Br(a)), 0.179; and Nak(a), 0.874. The distribution of HPA's for Chinese differ from those for Caucasians and for Japanese. When compared to Caucasians, Chinese show a higher prevalence of HPA-la (P1A1), higher prevalence of HPA-5b (Br(a)), lower prevalence of HPA-2b (Koa or Siba) and lower prevalence of HPA-3a (Baka). Both Chinese and Japanese have a very high prevalence rate of HPA-la (P1A1), ie. close to 100%. However, the prevalence of HPA 2-2b (Koa or Siba) and HPA-4b (Yuka) is slightly lower in Chinese than in Japanese; and, the prevalence rate for HPA-3a (Baka) is slightly higher in Chinese than in Japanese. PMID- 1306150 TI - Reoviruses: replication and molecular pathogenesis. AB - The mammalian reoviruses serve as a model for understanding both how viruses multiply within cells and, at a higher level of complexity, how the virus is assembled to "deliver" the virus to the cells in the host in which they can multiply and cause disease. They thus serve as a model for the molecular determinants of viral pathogenesis. PMID- 1306151 TI - Bactericidal activity of imipenem compared to erythromycin against intracellular Legionella pneumophila. AB - Pneumonia is the leading cause of death due to nosocomial infections with mortality ranging from 30 to 70%. Because imipenem has potent in vitro activity against virtually all major causes of nosocomial pneumonia, including P. aeruginosa, S. aureus, members of the family Enterobacteriaceae, and anaerobic organisms, it is used by many physicians as the empirical therapy of choice in severe nosocomial pneumonias. Recognition of Legionella species as nosocomial pathogens has been increasing. The incidence of Legionnaires' disease among patients with nosocomial pneumonia is reported to be as high as 30% (1), but the real prevalence is unknown. Imipenem has bactericidal activity against Legionella in vitro but has not previously been tested for efficacy against intracellular Legionellae. PMID- 1306152 TI - Efficacy of L-627, a new carbapenem, in the treatment of experimentally induced intra-abdominal infections in rats. AB - A reproducible experimental model of intra-abdominal infections in rats has been devised in order to simulate intra-abdominal sepsis in patients. Pre-operatively, the rats were fed lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was re-established by an end-to-end anastomosis. The segment of ileum was then returned to the abdominal cavity. This experimental model was used to compare the efficacy of L-627 with the combination of gentamicin plus metronidazole. Eighty per cent of the untreated animals died within three days. Animals treated with L-627 or gentamicin plus metronidazole had significantly decreased mortality and increased cure rates during the experimental period. Only two animals in the two treatment groups died. L-627 seems to be as useful as gentamicin plus metronidazole in the treatment of intra abdominal infections. PMID- 1306153 TI - Efficacy of subinhibitory concentration of pefloxacin in preventing experimental Staphylococcus aureus foreign body infection in mice. AB - Adhesion is the first step leading to colonization and infection of a foreign body (FBI). To assess the ability of a subinhibitory concentration (subMIC) of pefloxacin (P) to prevent such infection, an experimental model was developed in Swiss albino mice. Subcuts of polyurethane catheters (Vygon) were placed in the peritoneal cavity of animals and 24 hours later, different inocula of an adherent strain of Staphylococcus aureus (SA) (MIC of P:0.8 mg/l) were injected i.p. Unexposed SA served as controls. Two days later the removed catheters, blood and spleen specimens were quantitatively cultured for bacterial content and identity. Infection was defined as more than 10 CFU/ml of SA recovered. Significant protection of mice, with lower dissemination, was found with inoculum sizes of 10(5) and 10(6). These results suggest that subMICs of P may confer protection against foreign body infection. PMID- 1306154 TI - Experimental chemotherapy of leishmaniasis with adenosine analogue Formycin A, in combination with inhibitor of nucleoside transport, nitrobenzylthioinosinate. AB - A single dose of the adenosine analogue Formycin A (FoA) (20 mg/kg), combined with nitrobenzyl mercaptopurine ribonucleoside 5'-monophosphate (NBMPR-P) (10 mg/kg), a prodrug of nitrobenzylthioinosine (NBMPR), was effective in reducing the size of the foot pad lesions from 7.4 +/- 0.2 to 3.9 +/- 0.2 of Syrian golden hamsters infected with Leishmania major. There was a statistical difference (p < 0.01) in the size of the foot pad by the fifth day between the infected groups that received treatment and the controls, as well as between the groups that were treated with combined drugs and FoA only. The initial reduction in size of the foot pad noted in the group that received only FoA was transient. The effect of FoA or FoA combined with NBMPR on the in vitro cultured promastigotes was similar, indicating that the transport inhibitor might be manipulating the availability of FoA in the host's macrophages where the leishmania amastigotes are resident. The results further indicate the need to explore the usefulness of combining cytotoxic nucleoside analogues with host protecting nucleoside transport inhibitors in the treatment of protozoan parasitic infections. PMID- 1306155 TI - The efficacy of clarythromycin (A-56268, TE-031) in the treatment of genital chlamydial infection. AB - The authors report the preliminary results of an experience of treatment with clarythromycin in Chlamydia trachomatis endocervicitis/endourethritis; 100% of 51 outpatients treated had negative ELISA results 7-10 days after the end of treatment with clarythromycin 500 mg. b.i.d. for 7 days. Among 64 female outpatients with chlamydial cervicitis treated with erythromycin 1 g b.i.d. for 7 days, 88% were negative at ELISA at the same intervals after therapy. The authors conclude that the efficacy of clarythromycin in this experience makes it use worthy of other and more extensive studies. PMID- 1306157 TI - Effect of carnitine and coenzyme Q10 on the calcium uptake in heart sarcoplasmic reticulum of rats treated with anthracyclines. AB - The effect of the association of carnitine and coenzyme Q10 on doxorubicin cardiotoxicity has been investigated. The two drugs administered to rats for two weeks have lower protective activity when they are administered separately rather than given in association (carnitine 200 mg/kg/day, coenzyme Q10 10 mg/kg/day) for the acute toxic effect of doxorubicin on perfused functioning isolated hearts. The sarcoplasmic reticulum damage measured by calcium-uptake is lower in rat hearts treated with the combined drugs. Deferoxamine and phosphocreatine, two compounds which protect from peroxidative damage due to iron and copper ions, show very strong protection from acute doxorubicin toxicity in isolated perfused hearts. Carnitine and coenzyme Q10 do not protect sarcoplasmic reticulum from iron ions damage, suggesting that their mechanism of protection is not directly related to peroxidation due to metal ion-dependent cardiotoxicity of doxorubicin. PMID- 1306156 TI - L-carnitine and coenzyme Q10 protective action against ischaemia and reperfusion of working rat heart. AB - The protective effect of L-carnitine, coenzyme Q10 and their combination on haemodynamic and metabolic variables has been investigated in isolated perfused working rat hearts after 10 min of global normothermic ischaemia followed by 60 min of reperfusion. In untreated rats or in rats treated only with L-carnitine or with coenzyme Q10, this experimental condition did not induce any irreversible myocardial injury as measured by leakage of cardiac enzymes; however, it decreased some haemodynamic parameters such as cardiac output and minute work, as well as the ATP concentration and the total adenine nucleotide pool. No variations in haemodynamic and metabolic parameters were observed in the rats treated with L-carnitine plus coenzyme Q10. In the perfusate of the hearts of the rats treated with both compounds, a lower purine release (a good index of myocardial energy balance) was also obtained. Although the molecular mechanisms remain to be defined, it appears that the association of L-carnitine and coenzyme Q10 is more effective than using these compounds separately. The complementary and synergic actions of L-carnitine and coenzyme Q10 on metabolism and against peroxidation by oxygen reaction species may explain the efficacy of their association. PMID- 1306159 TI - Expression of the PMP-22 gene in Trembler mutant mice: comparison with the other myelin protein genes. AB - The Trembler mouse suffers from a dominantly inherited autosomal mutation affecting the Schwann cell activities, which results in an abnormal myelination of the peripheral nervous system. Very recently, it has been shown that the mutation is in the PMP-22 gene. However, the level of expression of the mutated gene in trembler mice has not been studied. Therefore, we measured the steady state levels of mRNA encoding PMP-22 in the sciatic nerve of normal and trembler mice, and we compared these results with the steady-state levels of mRNAs encoding the major peripheral nervous system myelin proteins. Our results show that all the myelin protein genes studied are affected by the trembler mutation but to a different extent, and that the PMP-22 gene is expressed at very low levels in the trembler nerve. This suggests that regulation of the expression of the PMP-22 gene is altered in the Trembler mutant. PMID- 1306158 TI - Myelin palingenesis. 2. Immunocytochemical localization of myelin/oligodendrocyte glycolipids in multilamellar structures. AB - Myelin is a membrane with unique characteristics that set it apart from any other membrane. It has a very high lipid:protein ratio (approximately 75:25) not found in other multilamellar membranes; it has a high content of two glycolipids- galactocerebrosides and sulfatides--which account for 26.5% of its lipids. The physiological role of these glycolipids in myelin and/or oligodendrocytes is unknown, but evidence that Abs directed against them interfere with myelination has been presented. Moreover, one of the early events in the process of oligodendrocyte differentiation prior to myelination is the acquisition of galactocerebroside on their surface. In earlier work, we have demonstrated that adhesion of oligodendrocytes to a positively charged substratum signals the commencement of myelinogenesis. Among the events that take place following adhesion are the rapid synthesis of glycolipids. Since over time in culture, oligodendrocytes elaborate multilamellar membranes that contain all the myelin characteristic proteins, we undertook to investigate whether these structures also accumulate myelin characteristic glycolipids. We have used three monoclonal antibodies--two are directed against galactocerebroside, the third one is an antisulfatide--in conjunction with the immunogold method, at the electron microscopic level, to examine the distribution of these glycolipids in the multilammelar structures that accumulate in long-term oligodendrocyte cultures. Our data show that galactocerebrosides and sulfatides are present in the multilamellar structures. Staining is easily demonstrated on the outermost membrane. However, as was the situation with myelin proteins, detection of these glycolipids on the inner lamellae is only achieved at the expense of destroying the ultrastructure. This is so, independent of whether the structures are compact or not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306160 TI - Developmental expression of glial fibrillary acidic protein and actin-encoding messages in quaking and control mice. AB - Quaking is a neurological mutation leading to pleiotropic phenotypic expression, the most prominent being disturbed myelin formation in the central nervous system (CNS) with minor abnormalities in the peripheral nervous system. Previous immunochemical measurements of glial fibrillary acidic protein (GFAP) revealed a marked increase in the protein in several areas of the CNS. To further characterize the regulation parameters of GFAP synthesis, we analyzed the levels of GFAP mRNA in 5 regions of the CNS, some with elevated levels of GFAP and some without. This was compared to the developmental expression of GFAP transcripts in the same regions in normal mice. To establish the specificity of the variations observed with this astroglial specific message, we conducted a similar investigation with actin RNA which is expressed by several cell types in the CNS. Both the actin and the GFAP message were found to be increased in the adult mutant throughout the CNS. In 2-year-old normal mice the messengers for both cytoskeleton proteins were expressed in a higher amount than in young adults. PMID- 1306161 TI - Neural cell adhesion molecules are present in the fetal human primary olfactory pathway. AB - Olfactory tissues from human fetuses (17.5-28 weeks of gestation) were stained by immunofluorescence for neural cell adhesion molecules (N-CAMs). Staining for N CAMs was most prominent in the olfactory nerve bundles in the lamina propria, while in the olfactory epithelium, it was present on the olfactory receptor neurons and globose basal cells. The basal cells proper and supporting cells lacked N-CAMs. In the olfactory bulb, only the olfactory nerve and glomerular layers showed moderate labeling for N-CAMs. Western blot analysis showed that the N-CAMs of the fetal human primary olfactory pathway consisted of three molecular isoforms, N-CAM180, N-CAM140 and N-CAM120. PMID- 1306162 TI - Norepinephrine utilization in the hypothalamus of the male rat during adolescent development. AB - This study examined the influence of adolescent development and pubertal changes in gonadal function on the development of norepinephrine (NE) turnover in the hypothalamus and cerebral cortex of rats from late juvenile to young adult ages. In one study, NE utilization was estimated in intact male rats and in male rats castrated at 14 days of age. NE levels were measured 15, 30, 45, 60, 120, and 240 min after inhibition of catecholamine synthesis at 28, 42, and 70 days of age. In a second study, male rats were made precocious by chronic testosterone exposure over days 14-28 and on the 28th day NE utilization was measured in both the hypothalamus and cerebral cortex. Turnover rates were calculated based on steady state kinetics. The results indicate that in vivo NE levels and turnover rates in both the hypothalamus and cortex significantly increase from a late juvenile age to adulthood. However, when NE levels measured after synthesis inhibition were expressed as a percentage of the mean basal values, there was a significant effect of age only in the hypothalamus. Hence, the age-related increases in hypothalamic NE turnover appear to reflect age-related changes in NE utilization, whereas the increases in cortical turnover rates reflect the increasing basal levels and not age-related changes in NE utilization. During mid-puberty (42 days), NE utilization in the hypothalamus was markedly different from that observed in this region at either 28 or 70 days. At 28 and 70 days, NE levels decreased to 50% of basal levels by 4 h following synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306163 TI - Development of the paramedian lobule of the cerebellum in wild-type and tottering mice. AB - The mutant mouse tottering, (tg/tg), and the compound heterozygote mouse (tg/tg1a) exhibit three neurological disorders: ataxia, petit mal-like absence seizures and myoclonic intermittent movement disorders which are independent of the absence seizures. The tottering mouse carries an autosomal recessive single gene mutation on chromosome 8, and behavioral symptoms are first observed in the 3rd to 4th week of age. Using an additional genetic marker, Oligosyndactyly (Os), it is possible to distinguish tg/tg and tg/tg1a mice from wild-type mice at birth; nonaffected heterozygous littermates carry the Os mutation while tottering and compound heterozygous mice do not carry the Os gene. Similar to neurons found elsewhere in the brain, cerebellar Purkinje cells in both the wild-type and mutant mice were found to decrease in diameter with maturation. Forebrain weight, hindbrain weight, Purkinje cell dimensions and the thickness of the molecular layer in the paramedian lobule of the cerebellum in mutant mice were found to be reduced in mutants after, but not prior to the onset of behavioral symptoms. PMID- 1306164 TI - Effects of neonatal asphyxia on the serotonin neuron system in the developing brain studied by immunohistochemistry. AB - The effects of neonatal asphyxia on the serotonin neuron system were examined using the immunoperoxidase method. Male mice, 2 days of age, were exposed to total asphyxia (100% CO2) for 30 min. Mice that spontaneously survived were perfused transcardially with a fixative at 15, 30 and 60 days of age. Quantitative immunohistochemical analysis at 60 days of age demonstrated a significant decrease in the numbers of serotonin-immunoreactive cell bodies in the nucleus raphe dorsalis, the nucleus raphe pontis, the subpyramidal region, the total raphe system and the whole brain, while no significant reduction in the number of serotonin-immunoreactive cell bodies was observed in the caudal raphe system. Presumably degenerative changes in serotonin-immunoreactive fibers were observed in various parts of the brain of mice subjected to total asphyxia at 15 days of age, and the numbers of degenerated fibers decreased in almost all parts of the brain, the exception being the caudal portion of the brainstem, at 30 and 60 days of age. These results suggested that neonatal asphyxia induced permanent changes in the serotonin neuron system, with regional differences. PMID- 1306165 TI - [The epidemiology and risk factors, in particular environmental, of malignant non Hodgkin's lymphomas. The Working Group on the Epidemiology of Tumors of the Hemo- and Lymphopoietic Systems in Italy]. AB - Malignant non-Hodgkin's lymphomas (NHL) represent a category of neoplasms that includes several types of tumours with different hystological and clinical characteristics. No large differences exist in incidence and mortality for the whole category of lymphomas among different countries. On the other hand data concerning different subclassifications of lymphomas in different countries are not available. The incidence of NHL increased in recent years in USA and in the European countries. Data from the Cancer Registry in the province of Varese, the registry with the longest high-quality registration period in Italy, indicate the same tendency. Also mortality rates show an increasing trend in Europe and in the USA. The cause of changing in incidence and in mortality rates for NHL are unknown. Anyhow many factors, viral, chemical and immunological are known to be associated to the occurrence of lymphomas. Risk factors and in particular environmental factors are reviewed. Problematic aspects, in relation to methodologies adopted in these studies, are focused. PMID- 1306166 TI - Health effects of the Bhopal gas leak: a review. AB - The methyl isocyanate (MIC) gas leak from the Union Carbide plant at Bhopal, India in 1984 was the worst industrial disaster in history. Exposure estimates of gas concentrations in the area range from 85 to 0.12 ppm. Of the approximately 200,000 persons exposed, 3598 deaths have resulted as of November 1989. Chronic inflammatory damage to the eyes and lungs appears to be the main cause of morbidity. Reproductive health problems in the form of increased spontaneous abortions and psychological problems have been reported. Questions about the nature of MIC toxicity have been raised by the persistence of multi-systemic symptoms in survivors. Animal studies using radio-labeled MIC given by the inhalation route have shown that the radio-label is capable of crossing the lung membranes and being distributed to many organs of the body. This paper reviews health effects of gas exposure from published studies and discusses some of the clinical and epidemiological issues being debated. PMID- 1306167 TI - [The quality of the data on hospital discharge]. AB - Methods and results of a study on quality of the hospital discharge data are described. The study has been performed in the Hospital of Padova (Italy) and carried out on charts of all patients discharged in 1988. The completeness of discharge forms compilation, the appropriateness of diagnosis and surgical procedures coding, the correspondence between discharge forms and medical record data, the correspondence between discharge forms and computerized data have been analyzed. Four thousand seven hundred seventy six discharge forms were analyzed and 1226 (26.2%) showed one or more errors. Coding procedures have been incorrect in 18.6% of the cases. Improvement actions which have been adopted are described. PMID- 1306168 TI - [Major ambulatory surgery: organizational models]. AB - In this essay, the authors provide a definition for those medical care facilities representing a consolidated alternative to traditional hospitalization. These facilities can be basically ascribed to the following patterns: day case surgery; day-hospital activity; home-care. Day case surgery is a complex and, in most cases, interdisciplinary procedure; this type of activity necessitates a pre hospitalization period and often also a "protected discharge" or even a home-care service. Some specific criteria regarding day surgery activity have been defined as follows: the main criteria have a clinical nature, but they interact with others belonging to a social and structural-organizational order. The Royal College of Surgeons of United Kingdom has officially recognized in 1985 this medical care typology as one of the constituents of surgical care, and has evaluated that at least 1/3 of the overall operations could be carried out as day care surgery. In the United States, besides hospital and ambulatory surgery activity, a new pattern known as "free-standing center" has been promoted; in 1993, 35% of the operations is expected to be carried out in day case surgery centers. As far as Italy is concerned, in 1988 only day-hospital practice has been adequately recognized as an alternative medical care facility to traditional hospitalization. The Emilia Romagna region, in order to increase day case surgery activity, has issued in 1991 a list of 53 DRGs, in which day bed units treatment was possible. Up to now, however, only a small part of these diseases is treated on a day case surgery basis. PMID- 1306169 TI - [An operating model for assessing the practical efficacy of screening tests: the case of amblyopia]. AB - Standard for assessing the efficacy of screening programs are at present well established. Nevertheless, the effectiveness of screening programs can reduced by several factors in real world conditions. The aim of this work is to check the feasibility of an operational model for the practical evaluation of the effectiveness of screening programs. In this model seven critical points are defined (recruitment, screening test sensitivity, access to diagnostic services, diagnosis, compliance to follow-up, treatment compliance, therapy) and their contribution to the reduction of potential effectiveness is calculated. For each point consequent problem(s) and possible solutions are predefined. The model was tested with the results of the screening program for amblyopia of the Community Health Service of USL 32 Treviglio (BG) assuming 40% and 97% sensitivity of the screening test. For this screening the reduction of effectiveness at the seven critical points ranged from 0 to 60%, with a total reduction of effectiveness to 15.6-37.8%. The operational model was used to identify causes of this reduction. This kind of analysis is proposed as a tool for evaluation and improvement of the effectiveness of efficacious screening program. PMID- 1306170 TI - [Social differences in infant mortality in a longitudinal Turin study]. AB - The Turin longitudinal study enables to study the one-year survival of children born to any member of the study population and to relate the still-born and infant mortality to the parents' census characteristics. In this paper 25,108 children, born between 1981 and 1985 of parents residents in Turin at the 1981 population census, were followed up with respect to one-year survival. The numbers of infant deaths have been observed according to parents' education, housing ownership, occupational status and professional position. Only parents' education showed consistent differential in the still-born and infant mortality risks, adjusted for maternal age. PMID- 1306171 TI - [Malaria imported into Turin: epidemiological observations (1980-1990)]. PMID- 1306172 TI - [An active offer of DPT vaccine and the response of the population in Local Health Unit 63 of the Piedmont Region, Saluzzo]. PMID- 1306173 TI - [Uncertainty: a parameter difficult of communicating through the risk message]. AB - The theme of communicating uncertainty in messages of risk is examined in terms of the dominant goal of mobilizing action. Voluntary and involuntary "noises" compromise the efficiency of the communication process and are jointly responsible for several biases, at different levels, channels and agents, in messages of risk. A further source of confusion lies in how a message of risk is lived by the single individual--whether he/she identifies him/herself as the specific object of risk, or rather interprets risk as a mild probability diffused among a vast population. PMID- 1306174 TI - Maternal differences in infant carriage in golden-headed lion tamarins (Leontopithecus chrysomelas). AB - Infant-carrying behaviour was observed in two families of captive golden-headed lion tamarins. Although the young were raised in almost identical social situations, we found a reversed involvement of mother-father pairs in the amount of time they carried their offspring. In one case, the parental division of carrying behaviour was consistent with the standard description for callitrichids in that the adult male was the primary carrier. In the other family, the mother carried the infant considerably more than the male. Comparison of transfer initiations and transfer times showed that maternal choice operated. It is suggested that maternal behavior may depend primarily on the female's physical and hormonal condition. PMID- 1306175 TI - Olfactory communication among Costa Rican squirrel monkeys: a field study. AB - Behaviors with a possible role in olfactory communication among troop members were investigated as part of a field study on the reproductive and foraging ecology of squirrel monkeys (Saimiri oerstedi) in Costa Rica. All age classes engaged in the olfaction-related behaviors. Apart from olfactory investigation of female genitals by males during the mating season, no other potential olfaction related behavior (urine wash, branch investigation, rump, chest, back rub and sneeze) exceeded 1% of mean behavioral samples. Assessment of reproduction condition appears to be the primary function of such olfactory investigation of the female genital region. The primary function of urine washing is suggested to be the general communication of reproductive status, possibly facilitating reproductive synchrony. Sneezing, rump, back and chest rubbing do not appear to deposit substances active in olfactory communication. PMID- 1306176 TI - Marking behaviour in two lemur species (L. fulvus and L. macaco): relation to social status, reproduction, aggression and environmental change. AB - The influence of social status, reproductive and agonistic contexts and environmental change on scent-marking and allomarking rates were studied in captive groups of Lemur fulvus and Lemur macaco. No evidence of female social dominance over males appeared in either species. In L. fulvus, intrasexual relationships were characterized by the dominance of one adult male over another and by the existence of female affiliative association ('central' vs. 'peripheral' females). In L. macaco, no intrasexual dominance relationships were apparent except for a brief ostracism of one female. In both species, (1) intrasexual differences in social status were related to differences in marking rates, (2) no direct relation appeared between marking rates and aggression or reproduction, (3) allomarking was not differentially directed towards specific individuals and (4) physical environmental factors clearly influenced scent marking and allomarking rates. These results are discussed in relation to the possible functions of marking behaviour in intragroup relations. PMID- 1306178 TI - Use of resources by free-ranging female langurs (Presbytis entellus) during different reproductive phases. PMID- 1306177 TI - Assessment of factors responsible for variability of birth weight in the long tailed macaque (Macaca fascicularis). PMID- 1306179 TI - Fine structure of the vomeronasal organ in the common marmoset (Callithrix jacchus). PMID- 1306180 TI - Shape of the craniofacial complex in children with Turner syndrome. AB - The shape of the craniofacial complex was established in 69 children with Turner syndrome aged between 3.5 and 16.6 years. The children had not been treated with growth hormone (GH) or anabolic steroids. On a standardized lateral roentgenencephalogram 13 linear and 7 angular variables were measured. Data of all variables were available from normal Dutch children for comparison. The main abnormalities were located in the cranial base and in the mandible and consisted of a short posterior cranial base, all increased cranial base angle and a short, retrognathic and posteriorly rotated mandible. The maxilla was smaller than normal and also slightly posteriorly rotated. The abnormalities were already present in young children with Turner syndrome. Indications were found that in Turner syndrome interstitially as well as appositionally growing cartilage is affected. The changes in the maxilla can be explained in various ways. They may be due to defective growth of the nasal cartilage or to a disorder in the intramembranous ossification of the maxilla or they may be adaptive to the changes in the cranial base and the mandible. From this study it can be concluded that patients with Turner syndrome exhibit several craniofacial abnormalities, probably due to a cartilage disorder. PMID- 1306182 TI - Presence of multinucleate cells in the papillary layer of the Macaca fuscata enamel organ. AB - The enamel organ of Macaca fuscata from post-secretory transition to the early maturation stage of was investigated by means of light and electron microscopy. Unusual, large multinucleated cells were observed in the papillary layer. These cells contained organelles characteristic of the maturation stage ameloblast and often extended to the enamel surface, suggesting a possible origin from the ameloblast layer. PMID- 1306181 TI - Effects of lip adhesion and presurgical orthopedics on facial growth: an evaluation of four treatment protocols. AB - Differences in craniofacial morphology in uni and bilateral cleft lip and palate were studied by roentgenocephalometry: 35 American children, treated with a lip adhesion procedure, and 26 Dutch children treated with a preoperative orthopedic procedure, both followed by a lip and/or palatal repair, were compared. A multivariate statistical approach was used to study the effects of the surgical procedures and of the age of the child when operated upon. The variables affected by the type of operation were: the relative length of the maxilla (PNS-ANS); the SNA angle; and the relative length of the mandible (Go-Po). The length of the maxilla was on average longer for those treated with preoperative orthopedics and the maxilla was largest for children whose hard palate had yet to be closed. This was also the case for the SNA angle except for children treated with the combined lip-soft palate closure procedure. The mandible followed pattern displayed by the maxillary length; it was larger for those treated with preoperative orthopedics. Significant effects of the timing of the surgery on the variables studied were also found. Postponement of the definitive lip closure resulted in a reduction of the maxillary length, whereas delay of soft palatal closure resulted in an increase of the maxillary length. PMID- 1306183 TI - The relation between the response properties and the position of reinnervated periodontal ligament mechanoreceptors in the cat. AB - Electrophysiological recordings were made from functional single fibres teased from the inferior alveolar nerve 12 weeks after nerve section. The force thresholds, adaptation times and conduction velocities of 10 located periodontal ligament mechanoreceptors in 2 cats were recorded and compared with results for normal located receptors from a previous study using similar techniques. The relation of both threshold and the adaptation rate to the position of the reinnervated receptors was statistically significant and similar to the relation for normal units. These results support the hypothesis that the range of response characteristics of periodontal ligament mechanoreceptors depends on their position relative to the tooth's fulcrum. PMID- 1306184 TI - Critical analysis of an experimental set-up generally used for the permeability evaluation of dental lining material. AB - The diffusion constants of iodide through dentine membranes were determined. The DI-values were within the range generally obtained by other investigators. When the estimation of the diffusion coefficient through a well defined polycarbonate membrane was calculated the value was strongly affected by the diffusion through the unstirred diffusion layer. By using such an experimental approach it seems necessary to develop a new cell equipped with a double stirring system (one in each compartment) in order to reduce strongly the thickness of the unstirred diffusion layer. PMID- 1306185 TI - [The orodental status of a population of school children in the southeast of France in 1991]. AB - An epidemiological survey was conducted in 1991 in the South-East of France in order to estimate the oral health conditions of a sample of 6-15 year old children. The caries prevalence of 457 subjects was presented as mean values of the dft, dfs, DMFT and DMFS indices. The dft and dfs indices decreased from the age of 6 years and the mean number of decayed surfaces of deciduous teeth was always lower than two. First carious lesions in permanent teeth were diagnosed at 6 years, but no filling was observed before 7 years. The fissure caries were the most frequent. Extractions for caries were very rare. The comparison of this study with a similar one made in 1987 showed a reduction in caries more important in the permanent teeth. A decrease in the number of decayed surfaces was also observed. This improvement in oral health seemed to be mainly related to better oral hygiene and an increase in the use of fluoridated dentifrices. PMID- 1306186 TI - A simple stimulator for periodontal mechanoreceptors in human subjects. AB - Mechanoreceptors in the periodontal ligament are activated by tooth movements as little as 1-3 microns. It has been difficult in the past to move a tooth only over this small distance in order to activate the periodontal receptors without at the same time activating other receptors in related structures. This paper describes a simple solution to this problem based on the use of von Frey hairs (in the form of nylon filaments) rather than a rigid probe, to move the tooth. Filaments of different stiffness are mounted on the moving coil of a loudspeaker to apply different forces to the tooth. The timing of the contact of the filament with the tooth is measured precisely with a simple impact detector. The sensation elicited by this stimulator is abolished by local alveolar anaesthesia, indicating that the stimulation was localised to the periodontal area. The flexible probe is an important safety feature, as it limits the force applied to the tooth, and therefore the distance that the tooth can be displaced. The stimulator, suitable for psychophysical studies on the thresholds of periodontal receptors, on the reflex responses to stimulation of periodontal mechanoreceptors, and teaching applications, can be constructed from readily available components at minimal cost. PMID- 1306187 TI - Cariogenic changes in dental enamel of boys and girls in relation to salivary properties. II. Radiological examination. AB - In earlier clinical studies of a group of children subjected to an intense fluoride treatment programme several salivary properties were related to cariogenic changes in the enamel surface, as assessed by mirror and probe. In this study the relationship between salivary parameters and cariogenic changes was investigated on bitewings taken from the same teeth. Inverse correlations were found between the acid producing capacity of the micro-organisms in the saliva (as determined in the Snyder test) and most cariogenic changes detected in bitewings particularly in boys. These radiologically detected changes in enamel were the reverse of those obtained clinically. These discrepancies were explained by differences in sensitivity between clinical and radiological techniques used to diagnose cariogenic changes. In contrast it was confirmed radiologically that for girls the P concentration in saliva and for boys the amount of resting saliva are important for preventing extension of caries into deeper layers of enamel. PMID- 1306188 TI - Susceptibility of Candida albicans to peroxidase-catalyzed oxidation products of thiocyanate, iodide and bromide. AB - The susceptibility of Candida albicans (ATCC 10231 and wild strains) to hypo(pseudo)halous ions (OSCN-, OBr-, OI-) produced by the lactoperoxidase system was tested. Six strains of Candida albicans were isolated from swabs taken from the mouths of children with orthodontic appliances and selected on Sabouraud Chloramphenicol-Actidione agar plates. The survival rate of Candida blastospores after a 30 min exposure to lactoperoxidase system ranged from 79 to 105% in the presence of 615 microM thiocyanate, from 56 to 88% in the presence of 345 microM bromide and from 0 to 4% in the presence of 250 microM iodide. Results showed that only OI- could exert a strong inhibiting effect in vitro on Candida albicans at physiological concentrations. Nevertheless, the activity of the hypoiodite generating system in saliva was found to be under the control of thiocyanate concentration. PMID- 1306189 TI - Posterior reduction and stabilization of painful spondylolisthesis. AB - The authors reported 16 cases of first to third grade painful spondylolisthesis. The treatment was posterior reduction and stabilization in one stage operation by modified Vidal et al and Luque techniques. The operation consisted of stabilization of an above involved vertebra and another one below with a rectangular rod and sublaminar wirings. The pedicular screws were inserted through the Harrington hooks which levered upon the rectangular rod for reduction of the displaced vertebra. The posterolateral intertransverse arthrodesis of two spinal segments was also added. A 2-5-year follow-up study showed all patients were relieved from pain initially, and could ambulate early following the operation. The vertebral displacement did not increase postoperatively and solid posterolateral fusion was obtained. PMID- 1306190 TI - Microneurovascular decompression: early experiences in Srinagarind Hospital. AB - These results support other studies that indicate that M.V.D. is the best procedure to treat these patients. There are some points to emphasize M.V.D. in order to achieve the best results and lowest complication rate. These include good preoperative patient preparation; more lateral suboccipital craniectomy to expose the cranial nerves with minimal retraction; adequate drainage of CSF from the cistern before attempting to identify the nerve; thorough inspection of the affected cranial nerve, especially in the root entry (exit) zone; adequate mobilization of blood vessels and stable interposition of teflon felt between the blood vessels and the affected nerve. PMID- 1306191 TI - Computed tomography of spinal tuberculosis. AB - CT findings of 20 proven cases of tuberculous spondylitis were reported. Vertebral fragmentation and paravertebral abscesses were found to be important findings. CT should be performed in cases without characteristic plain radiographic features and in cases that the extent of the disease is to be evaluated. PMID- 1306192 TI - Determination of hemoglobin Bart's in alpha thalassemia traits by two-site immunoradiometric assay. II. Detection of hemoglobin Bart's in alpha thalassemia traits. AB - A sensitive method for the determination of minute amounts of Hb Bart's in hemolysate of alpha thalassemia-1 and alpha thalassemia-2 was carried out by two site immunoradiometric assay. This technique is very sensitive and is able to detect minute amounts of substances. When this method is used with specific anti Hb Bart's derived from affinity column chromatography, then labelled with radioactive 125I, the two-site immunoradiometric assay will contain both the sensitivity and specificity for the determination of Hb Bart's. In this study, parents of fetus with Hb Bart's hydrops fetalis contained high levels of Hb Bart's 0.73-1.11 per cent (mean +/- S.D. = 0.86 +/- 0.12%). Parents of Hb H diseases had Hb Bart's in two groups. The first group contained high levels of Hb Bart's of 0.73-1.20 per cent (mean +/- S.D. = 0.88 +/- 0.14%), while the second group had levels of 0.39-0.45 per cent (mean +/- S.D. = 0.42 +/- 0.02%). Mothers of patients with Hb H disease contained Hb Bart's of 0.42 +/- 0.48 per cent (mean +/- S.D. = 0.45 +/- 0.02%). Eight out of ten normal subjects contained low levels of Hb Bart's of 0.17-0.26 per cent (mean +/- S.D. = 0.22 +/- 0.04%), while two contained high levels of Hb Bart's of 0.46 and 0.43 per cent respectively. The two-site immunoradiometric assay was able to differentiate the level of Hb Bart's among alpha thalassemia-1, alpha thalassemia-2 and normal subjects. PMID- 1306193 TI - Vascular complications in noninsulin dependent diabetes mellitus (NIDDM) in Srinagarind Hospital, Khon Kaen. AB - We prospectively conducted a hospital based study to determine the prevalence of vascular complications in NIDDM and their risk factors. Using standard protocol for interviewing, physical examination and laboratory investigations, we studied 207 patients from the diabetic clinic and medical outpatient department (ratio 3.9:1) by systematic sampling. The prevalence of hypertension, coronary heart disease cerebrovascular disease, peripheral and large vessel disease was 22.2, 22.2, 8.2, 21.3 and 34.8 per cent respectively. We found that the prevalence of small vessel disease, retinopathy and nephropathy was 34.3, 25.1 and 12.5 per cent respectively. The complications were slightly higher in females and increased with duration of diabetes. By univariate and logistic regression analysis, we found that the risk factors of large vessel disease were body mass index, diastolic blood pressure, duration of diabetes and for small vessel disease were duration of diabetes and high uric acid. PMID- 1306194 TI - Prediction of low birth weight outcome in Thailand: multiple regression analysis. AB - In the present study the risk approach using maternal risk factors for LBW newborns in Thailand is applied. The study may be considered as a managerial tool for developing local strategies and is particularly useful in maternal and child health care. The main objective is to develop a model to predict LBW outcome with an aim to screen those at risk at the level of health centres, district and provincial hospitals. Using MLR analysis, it is concluded that Model I and Model II (Table 3 and 4) can be used to predict which pregnant women are likely to deliver LBW newborns. The prediction can be made as early as the first trimester. If the prediction is shown to be accurate, the two models will be very helpful for use in Thai people. For general use, the investigators believe that Model I will be appropriate for application at the level of provincial and district hospitals, while Model II should be used at the health centre level peripheral to the health delivery system. PMID- 1306195 TI - Outcomes of pregnancy in adult idiopathic thrombocytopenic purpura. AB - The outcomes of 39 pregnancies in 36 idiopathic thrombocytopenic purpura (ITP) patients were analysed. Among the 36 pregnant patients, 23 had active ITP (platelet count < 100,000 per mm3), 12 had inactive ITP, during pregnancies, while one patient had active and inactive ITP during each of her two pregnancies. Maternal bleeding during delivery occurred more commonly in thrombocytopenic patients and was more frequent by cesarean section than by vaginal delivery. There was a 56 per cent incidence of neonatal thrombocytopenia. Maternal platelet count had no predictive value for neonatal thrombocytopenia. There was no serious bleeding among neonates born from thrombocytopenic mothers. In our experience, vaginal delivery was a relatively safe procedure for delivering small neonates from multiparous ITP mothers. Cesarean section should be used to deliver relatively big neonates especially from primigravida ITP mothers and splenectomy should be done at the same time. PMID- 1306196 TI - Carbamate insecticide and myocarditis. AB - The report of a 25-year-old Thai woman who came to the emergency room of Chulalongkorn Hospital dead on arrival. The gross and microscopic anatomic findings of lungs were compatible with carbamate poisoning which was confirmed by the analysis of the liver. Another important finding was profuse myocarditis which might be another cause of death. We found no relationship between myocarditis and carbamate poisoning in previous reports. (Computerized search by Medline). PMID- 1306197 TI - True hermaphrodite, 46,XX/46,XY karyotype with surgical reconstruction of ambiguous genitalia: a case report and literature review. AB - A 17-year-old phenotypic female with ambiguous genitalia is presented. The patient complained of progressive dysmenorrhea, passing urine and menstrual blood through the same opening since menarche. Pelvic examination revealed and enlarged clitoris with prominent phallus, an enlarged right labio-scrotal fold with palpable gonad and a 3 mm diameter opening of both the urethral meatus and vaginal orifice at the vestibule. Chromosome analysis showed 46,XX/46XY karyotype. Laparotomy via right inguinal incision confirmed true hermaphroditism because of finding a right unilateral ovotestis. Factors leading to delay in presentation are discussed and the need for early diagnosis and management is emphasized. The clinical, cytogenetic features, gonadal histology and management are described and discussed. PMID- 1306198 TI - Intracerebral hematoma caused by sparganum: a case report. AB - Cerebral sparganosis is caused by migrating larvae of Spirometra mansonoides. This condition is rare. The presenting symptoms include headache, seizures and focal neurological deficit, which are due to a parasitic granulomatous space occupying lesion. The authors report a case of intracerebral hematoma, which has never been reported as a presenting symptom of cerebral sparganosis. The surgical treatment of this complicated condition yielded poor results when compared to previous reports of the uncomplicated condition. PMID- 1306199 TI - Seroprevalence of Toxoplasma gondii in pregnant women in Ubon Ratchathani province. PMID- 1306200 TI - Cavernous sinus tumors: neuroradiologic and neurosurgical considerations on 150 operated cases. AB - We reviewed the neuroimaging studies of 150 patients with cavernous sinus tumors operated on during an 8-year period. Meningiomas (66 cases), chordomas (18 cases), trigeminal neurolemmomas (12 cases), and chondrosarcomas (11 cases) were the most common diagnosed neoplasms. Neuroradiological findings are briefly described for each different kind of tumor encountered. The surgical impact of these findings is discussed. PMID- 1306202 TI - The changing panorama of shunt complications. Twenty-five years' experience. AB - The distribution of shunt complications is analyzed in a series of 226 children and infants out of a total of 978 shunt operations performed between the years 1965 and 1989. The rate of shunt infections and obstructions has decreased significantly during the last ten years while the rate of CSF overdrainage complications has increased. A policy of active, elective shunt revisions has led to a reduction in the total rate of shunt revisions required. As only minor changes in the shunts available and used have taken place during the period converted, it is concluded that the main reason for the changing panorama of shunt revisions lies in improved neuroimaging and a better knowledge of complying with shunt complications. PMID- 1306201 TI - Severe head injury in a paediatric population. AB - Forty eight, patients under fourteen years of age, with severe head injury, who were admitted to the Children's Hospital, over a a period of 4 years were studied. During the same period 2500 children with head injury admitted, an incidence 2% approx. The low mortality and the good prognosis of these children is pointed out. The literature is also reviewed and a few conceptions regarding treatment, age of the patients in various series and intracranial haematomas were reconsidered. Extradural and subdural haematomas are excluded from this particular study. PMID- 1306203 TI - Hydrocephalus, lumbar canal stenosis and Maroteaux-Lamy syndrome (mucopolysaccharidosis type 6). Case report. AB - A case of communicating hydrocephalus and lumbar canal stenosis in a child with mucopolysaccharidosis type 6 is reported. We review the literature and discuss the aetiology of communicating hydrocephalus in this condition. PMID- 1306204 TI - The role of CSF ventricular drainage in controlling intracranial hypertension in patients with brain lesions. Comparison of three methods. Preliminary results. AB - Results obtained with three different CSF ventricular drainage methods (intermittent with no outflow resistance, continuous against a positive pressure, continuous with pre-arranged positive pressure), were evaluated in fifty nine cases of traumatic cerebral lesions and spontaneous intracerebral hematomas with intracranial hypertension. Continuous CSF withdrawal gives better clinical results and is more effective in controlling intracranial pressure than intermittent drainage (50% vs 13% successes respectively). Results obtained with continuous drainage against a steady positive pressure and with a pre-arranged pressure ("tidal drainage") are almost similar. However an outflow resistance 3-5 mmHg higher than diastolic level of ICP represents a rational approach to the problem. PMID- 1306205 TI - Primary choroid plexus carcinoma in an infant. Report of a case evaluated by MRI. AB - Primary carcinoma of the choroid plexus is a very rare neoplasm. We report a 17 month old female patient who was evaluated by MRI. The tumor was gross totally removed and radiotherapy was given subsequently. CT and MR correlation and histopathological differential diagnosis criteria of such tumors are discussed with an emphasis on total tumor removal. New chemotherapy regimens are needed for better survival especially in cases of recurrences. PMID- 1306206 TI - Schwannoma of the cavernous sinus. Case report and review of the literature. AB - A patient operated on for a schwannoma entirely developed into the cavernous sinus is described. Abducens nerve is supposed to be the origin of the tumor, although it could not be identified during the operation. Schwannomas of the cavernous sinus are exceedingly rare lesions. Only four reports exist in the literature. In three cases the tumor arose from the abducens nerve, in one case probably from the trochlear nerve. Direct approach to the cavernous sinus has become possible in recent years, but preoperatively impaired cranial nerve function shows a slim chance of postoperative recovery. PMID- 1306207 TI - Chondroma of the cervical spinal canal. Case report. AB - The authors report a case of cervical spinal canal chondroma in a 28 year-old man. The tumor was removed completely. Only about 10 similar cases are reported up to now. PMID- 1306208 TI - Hard-rock spinal meningioma. Case report and review of the literature. PMID- 1306210 TI - [Genetic background of bronchial asthma]. AB - Familial aggregations and genes for atopy, airway hyperresponsiveness, and serum IgE were studied in 69 members of five atopic asthmatic families spanning three generations. Atopy was found in 68%, bronchial asthma in 26%, airway hyperresponsiveness in 45%, and positive mite allergen in 59%. Both atopy and airway hyperresponsiveness were inherited in an autosomal dominant fashion, but were not related to each other. No linkage was found of HLA with atopy and mite positivity. T cell gamma receptor gene (7p15), IL-3, IL-4, and IL-5 genes (5q23), and postulated atopic gene (11q13) were all not linked to atopy. However, alle 2.5 kb of 11q13 showed an association with serum IgE level. The beta 2 adrenergic receptor gene (5q31-32) was linked to airway responsiveness to inhaled beta 2 adrenergic agonist, and was associated with the occurrence of bronchial asthma. PMID- 1306209 TI - Benign solitary nerve sheath tumors of the spinal accessory nerve in the posterior triangle of the neck. Report of two cases. AB - A case of solitary schwannoma and one of solitary neurofibroma originating from the spinal accessory nerve in the posterior triangle of the neck are described. Location of such neoplasms in this region is exceptional. The authors emphasize the importance of accurately enucleating the mass; when it is impossible to preserve the continuity of the neural pathway, nerve repair should be considered. PMID- 1306211 TI - [Involvement of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans]. AB - In an attempt to elucidate the role of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans, we examined 17 healthy male volunteers for ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia on three separate days in a randomized, double-blind fashion. Pirenzepine, a M1 muscarinic antagonist which does not cross the blood-brain barrier, biperiden, another M1 muscarinic antagonist which is expected to penetrate into the central nervous system, or placebo was intravenously preinjected before the measurement of ventilatory responses. There were no significant differences in the mean magnitude of ventilatory responses among the three experimental days. However, despite the poor correlation between the magnitude of ventilatory response to hypercapnia in the placebo and pirenzepine studies, there was a significant correlation between them when the value in the pirenzepine study was expressed as % of control, value i.e., subjects with greater hypercapnic ventilatory response in the placebo study showed greater declines with biperiden. Since these relations were seen only for the ventilatory response to hypercapnia with biperiden, we suggest that a cholinergic mechanism, particularly the M1 muscarinic receptor, may be involved in chemoreception to CO2 in the central nervous system and constitute the neurochemical background for the interindividual variation in hypercapnic ventilatory response in humans. PMID- 1306212 TI - [Hypoxic ventilatory response and hypoxic depression]. AB - We investigated whether or not the adaptation of peripheral chemoreceptor (PCR) activity can contribute to hypoxic ventilatory depression (HVD) during sustained hypoxia for 20 min in both healthy subjects and patients with sleep apnea. Effects of HVD on diaphragm (DIA) and genioglossal muscle (GG) were also assessed. Withdrawal test, which is well established to solely represent the function of PCR, was repeatedly conducted at 5 and 20 min during sustained hypoxic condition. The results suggested that PCR did not play an important role in the development of HVD. When HVD ensued during sustained hypoxia, minute ventilation and EMGDIA were suppressed to the same extent in both groups. On the other hand, EMGGG was strongly and consistently attenuated in OSAS, whereas it was not always the case in healthy subjects. We speculate that treatment for hypoxic conditions can induce improvement of impaired regulation of breathing via central mechanisms, and it can be an important factor reducing the incidence and the severity of upper airway occlusion or collapse. PMID- 1306213 TI - [Respiratory control in diffuse interstitial lung disease]. AB - Whether the change of lung volume affect ventilatory responsiveness to chemical stimuli has not been studied in patients with interstitial lung disease (ILD). We measured the responses of minute ventilation (VE), tidal volume (VT), and occlusion pressure (P0.1) to hypercapnia (HCVR) and hypoxia (HVR) in these patients. Breathing efficiency (delta VE/delta P0.1) and effective compliance (delta VT/delta P0.1) were also measured under the same stimuli. 1) HCVR and HVR were measured in one female patient with hypersensitivity pneumonitis. VE responses during low VC phase (VC; 71% of predicted value) were similar to that during increased VC phase (VC; normal level) in both HCVR and HVR. However, VT responses of low VC phase were lower than those of increased phase, and P0.1 responses of low VC phase were higher than those of increased VC phase. Both breathing efficiency and effective compliance of low VC phase were lower than those of increased VC phase. 2) Thirty one patients with ILD were divided into two groups: low VC group; VC < 80% of predicted value, and normal VC group; VC > 80% of predicted value. HCVR and HVR were compared between two groups. Mean values of VE response to hypercapnia and hypoxia in low VC group were lower than those of in normal group, although they were not significantly different. VT response to hypercapnia and hypoxia were significantly lower of low VC group than those of normal VC group. Mean values of P0.1 responses to hypercapnia and hypoxia of low VC group were higher than those of normal VC group, although they were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306214 TI - [Hypercapnic and hypoxic ventilatory responses in patients with chronic obstructive pulmonary disease]. AB - In patients with chronic obstructive pulmonary disease (COPD), we examined ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR). HVR was with normal limits, although HCVR was decreased in half of the patients. The patients with COPD often developed oxygen desaturation during sleep. Also, they had severe hypoxemia during exercise. High responders both to HCVR and HVR had no hypoxic episode during sleep or exercise. We conclude that hypoxemia during sleep or exercise may be related to both HCVR and HVR. PMID- 1306215 TI - [Bronchial asthma]. AB - In the first study, to clarify whether increased vagal afferent activity contributes to the increase in ventilatory response to CO2 in patients with asthma, we examined the effects of prostaglandin E2 (PGE2) inhalation on the respiratory response to CO2 in seven normal subjects. After PGE2 inhalation, the ventilatory and occlusion pressure responses to CO2 increased significantly compared with those after saline inhalation, with no increase in respiratory resistance. These results suggest that increase in vagal afferent activity may play a role in the increased hypercapnic response during acute exacerbations of asthma. In the second study, to clarify the reduced respiratory chemosensitivity associated with asthma-related deaths, we examined the hypercapnic and hypoxic ventilatory responses in five patients with near-fatal asthma who were given artificial ventilation and/or became unconsciousness during an acute exacerbation of asthma. Hypoxic ventilatory response was significantly lower in these subjects than in patients with uncomplicated asthma and normal subjects, suggesting that lowered hypoxic ventilatory response may be related to death from asthma. PMID- 1306216 TI - [Effect of diaphragmatic fatigue on ventilatory response to carbon dioxide]. AB - To clarify the effect of respiratory muscle fatigue on ventilatory response to carbon dioxide, we performed CO2 rebreathing study before and after diaphragmatic fatigue in nine healthy males. Diaphragmatic fatigue was induced by inspiratory resistor loading and confirmed by the increase in Tension Time Index and the decrease in Pdi max at FRC. The effects of diaphragmatic fatigue were as follows: 1) S and B value of VE-CO2 curve did not change. 2) P1-CO2 curve shifted to the left but the slope of the curve did not change. 3) delta Ppl response to CO2 decreased, but delta Pdi response to CO2 did not change. 4) The increase in respiratory accessory muscle EMG was more prominent, compared to diaphragmatic EMG. 5) Rib cage movement became more marked. In conclusion, diaphragmatic fatigue (with 60 percent decrease in Pdi max at FRC) does not affect on ventilatory response to carbon dioxide. To maintain the homeostasis of the chemical ventilatory feedback system, diaphragmatic dysfunction is compensated by the increased activity of respiratory accessory muscles with possible increase in neural drive. PMID- 1306217 TI - [Exposure to high altitude: ventilatory control in relation to syndromes of high altitude]. AB - To investigate the role of hypoxic ventilatory response (HVR) in the pathogenesis of acute mountain sickness (AMS) and high-altitude pulmonary edema (HAPE), we performed two studies. In the first study, nine healthy male lowlanders were exposed to a simulated altitude of 3,700 m (485 Torr) for 24 h in a hypobaric chamber. Subjects (n = 4) with lower alveolar ventilation on arrival at 3,700 m subsequently developed more severe AMS 24 h after the exposure. The relative hypoventilation was related to the lower HVR measured at low altitude, suggesting a possible role of low HVR in AMS. In the second study nine lowlanders with a previous history of HAPE (HAPE-S) and six control subjects were exposed to a simulated altitude of 3,200 m (515 Torr). At low altitude, HVR (delta VE/delta SaO2) in HAPE-S was significantly lower than that of controls (-0.40 +/- 0.20 vs. -0.85 +/- 0.21 L/min/%, p < 0.01). At high altitude HAPE-S showed lower PaO2, higher PaCO2 and lower PAO2, compared with controls, i.e., relative hypoventilation. In one of the HAPE-S, who showed the lowest PaO2 at the simulated altitude, oxygen breathing resulted in a paradoxical increase in ventilation, suggesting hypoxic ventilatory depression. These two studies suggest that low HVR may a contributing rather than a critical factor in the pathogenesis of AMS and HAPE. PMID- 1306218 TI - [Hyperventilation syndrome]. AB - Of 16 patients with hyperventilation syndrome (HVS), 11 experienced hypoxemic episodes (defined as PaO2 < or = 60 Torr or SaO2 < or = 90%). To investigate the relationship between hypoxemia in HVS patients and their hypoxic ventilatory response (HVR), we examined 9 of 11 HVS patients who experienced hypoxemic episodes after acute hyperventilation attacks. In order to investigate the genesis of hypoxemia after hyperventilation, we also examined minute ventilation and visual analog scale (VAS) scores representing the sensation of dyspnea at the start and at 70% arterial O2 saturation (SaO2) during HVR in 9 normal subjects under isocapnia and hypocapnia following voluntary hyperventilation (VHV). The HVR of 9 HVS patients who experienced hypoxemic episodes was normal. In 9 normal subjects, minute ventilation and VAS scores representing the sensation of dyspnea at 70% SaO2 during HVR were higher under isocapnia than under hypocapnia following VHV (p < 0.01). VAS scores taken during the HVR immediately following VHV and at 70% SaO2 were not significantly different. HVR and VAS scores representing the sensation of dyspnea were decreased under hypocapnia following VHV. These reductions were thought to be the main factors responsible for the genesis of hypoxemia following acute hyperventilation attacks in HVS patients. We conclude that hypoxemia is an important clinical sign in HVS patients, and it is important to investigate the breathing and chemical drive under hypocapnia, in order to understand the chemical regulation of breathing in HVS patients. PMID- 1306219 TI - [Oxygen-conserving delivery system]. AB - Three methods for improving oxygen delivery efficiency--transtracheal oxygen therapy (TTO), reservoir cannula, and demand-pulse oxygen delivery--are currently available. We discuss our experiences of TTO and its characteristics compared with the other two methods. Since 1988, we have tried to apply TTO to the candidates for home oxygen therapy (HOT) fulfilling the following criteria: 1) good activity and enthusiasm to daily life, 2) high oxygen flow rate with nasal cannula, 3) complicating nasal disorders such as chronic sinusitis, or 4) suffering complications from nasal cannula therapy. We used a disposable 8-Fr feeding tube for a trnastracheal catheter. Patients were taught to change their catheters themselves every day by simply removing the old and reinserting the new catheter. We have experienced nine patients on HOT with TTO. A half to a third of the flow rate of nasal cannular was required with TTO to achieve an equivalent PaO2 level. In cases with hypercapnea, a persistent significant increase of PaCO2 was not found. We measured arterial blood gases, changing the distance from the tract opening to the catheter tip, and it was suggested that in each case there may be an optimum distance to achieve the highest PaO2 level. Seven cases received TTO for more than 18 months, a mean of 30.2 months (range 19.3-48.9) and HOT for a mean of 26.6 months. They all maintained a high degree of enthusiasm for TTO. Two cases could return to work. Five cases enjoyed active daily lives, such as shopping, going out for recreation, travelling, and attending concerts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306220 TI - [Home oxygen therapy using liquid oxygen system]. AB - Home oxygen therapy (HOT) for patients with chronic respiratory failure has been believed to increase the quality of life and to improve the prognosis of such patients. In Japan, HOT for chronic respiratory failure has been supported by health insurance since March 1985. Since then, patients with HOT have increased progressively, and it has been reported that there are now over 20,000 patients with HOT. The oxygen concentrator which extracts oxygen from atmospheric air has been commonly used as the oxygen delivery system. Recently the liquid oxygen system has provided an attractive, convenient source of oxygen. Since April 1990, HOT using liquid oxygen system has been supported by health insurance, and its use will become widespread in Japan. A major characteristic of this system is that oxygen condensed into a liquid form allows storage of a larger supply. This system consists of two parts: stationary type which stores the liquid oxygen, and a portable type which can easily be refilled with oxygen a larger source. In the present study, we examined the efficacy of portable liquid oxygen in 50 patients with chronic pulmonary diseases including patients with chronic respiratory failure who had PaO2 < 55 mmHg during air breathing. We measured changes of ten minutes walking distance (10 MD) and blood gas analysis with and without portable liquid oxygen. We also performed on estimation of efficacy of liquid oxygen by questionnaires in patients receiving liquid oxygen for HOT. We did not find a significant improvement of 10 MD with portable liquid oxygen, but found a significant improvement of arterial oxygen tension at the end of walking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306221 TI - [The introduction of home mechanical ventilation in Japan]. AB - In the same context as home oxygen therapy in Japan, there is an urgent need to establish a home mechanical ventilation (HMV) support system for clinically stable patients dependent on long-term mechanical ventilation who wish to spend their lives outside institutions; at home in the community. We have cared for 3 HMV cases as long as 8, 5 and 2 years. All patients suffer from respiratory muscle paralysis with chronic neuromuscular diseases and require CMV mode mechanical ventilation for 18 to 24 hours/day using electrically drived portable ventilators connected to a tracheostomy tube. They need no oxygen supplementation. All patients clearly expressed a desire for the life style with HMV. Their families as the main caregivers willingly received the necessary training and mastered the techniques quickly, including AMBU-bag manual ventilation for occasional ventilator troubles, and bronchial hygiene. Our experiences of three HMV cases may be local and limited, but reveal the potential significance and technological possibility for home application of the care techniques that have been developed on or in-patient basis. The nationwide surveys of the status of patients requiring long-term mechanical ventilation for more than 3 months of duration by Suetsugu et al. (supported by Respiratory Failure Research Council of Health and Welfare Ministry) (1987, 1988 and 1989) listed 53 HMV cases in 1989 and revealed a slowly increasing trend from the 17 cases in 1987. However, it is important to recognize that the true medicosocial establishment of HMV in Japan is still behind and should be an urgent goal of respiratory care programs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306222 TI - [Effect of home oxygen therapy on prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension]. AB - We prospectively elucidated the effect of home oxygen therapy (HOT) on the prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension. One hundred and twenty-seven patients with pulmonary hypertension (mean pulmonary arterial pressure > or = 20 Torr) participated in this study. Fifty-four patients had chronic pulmonary emphysema, 5 chronic bronchitis, 19 diffuse panbronchiolitis, 29 old tuberculosis, 8 pulmonary fibrosis, and 12 other diseases. Fifty-one patients died of respiratory failure. The survival curve of patients who received HOT was not different from that of patients who did not receive HOT, although FEV1 and PaO2, both prognostic factors, were significantly worse in the patients who received HOT than in the patients who did not receive HOT. In the patients with COPD, the survival rate of patients who received HOT was significantly higher than that of those who did not receive HOT. The mean survival time of the patients who received HOT was significantly longer than that of the patients who did not received HOT (1971 +/- 217 SEM days and 978 +/- 156 days, respectively). From these data, we conclude that HOT improves the survival of patients with chronic pulmonary disease, especially COPD, associated with pulmonary hypertension. PMID- 1306223 TI - [Psychosocial features of the patients with home oxygen therapy]. AB - Home oxygen therapy (HOT) has released patients with chronic respiratory failure (CRF) from hospitalization for the rest of their lives, and has brought some relief from their physical restriction due to CRF. However, some new psychosocial problems have arisen from this home care treatment. Research has been performed on 85 patients in our hospital by: (1) comprehensive psychosomatic questionnaire for patients with long-term oxygen therapy, (2) CMI, (3) SRQ-D (depression), (4) MAS and Questionnaire C of JMHW-CRF research group. The results of (1) indicated some problems in the majority of patients. Also in SRQ-D, about half of the patients showed a depressive state. In MAS, more than a few patients revealed a high anxiety level concretely, recognized psychosocial problems with loss of desire for treatment pessimism recording their prognosis, in addition to loss of QOL. All the above and an understanding by the staff of the psychosocial situation of patients and a grasp of their mental state are extremely important in the long-term care of HOT patients. PMID- 1306224 TI - [Nursing care of long-term oxygen individuals in the home]. AB - The system and experience of home care for patients with chronic lung disease in Urasoe Sougou hospital was reviewed from nursing points of view. Home oxygen care was started in October, 1984. The Health Care Department (HCD) was established in July, 1988 to provide both various home cares and daycare services for the aged. The number of personnel (public health nurses, registered nurses) were increased year by year to 15, include one physician as a medical director. They worked on a full-time basis in home care. The roles of the HCD in home oxygen care are 1) direct nursing services, medical and psychological assessment, consultation, education for patients in the home. 2) exchange informations, coordination and scheduling among physicians, in-hospital care team and durable medical equipment companies. Quality of care on 65 patients between before and after the establishment of the HCD were compared to assess the efficacy of system. Quality of care were measured by several items; 1, frequency of home visit. 2, medical, psychological assessment. 3, patient's ability to understand and accept the disease state and home care, to do self-responsible procedures (bronchial hygiene, medication, bathing, etc.), and to handle the equipment. 4, assessment on patient's daily activities and environments. After the establishment of the HCD, quality of care has been improved. On 10 patients in the remote locations or islands, the HCD exchanged informations and coordinated with the community public health nurses and local practitioners. These experience suggests full-time home care team like the HCD contribute to improve both quality of care and quality of life of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306225 TI - [Mechanisms of clearance of foreign bodies by macrophages]. AB - Macrophages have specific functions related to the sites where they are found. Pulmonary alveolar macrophages (PAM) may play an important role the clearance of invading and degenerative substances from the alveolar spaces. To clarify the mechanisms of the clearance by macrophages, we studied the role of scavenger receptors (SR) and Fc receptors (FcR) of PAM. 1) SR: Expression and localization of SR in human PAM. Type I and II SRs were expressed in human PAM, and the two SRs were confirmed in the same cells by double staining method using polyclonal antibodies to the SRs. These SRs were localized on the cell membrane and the endosome in part. The expression of SR in PAM from normal nonsmokers, smokers and patients with pneumoconiosis was studied, but there were no differences among these groups. Kinetics of SR and acetylated low density lipoprotein (acLDL) in PAM. SR recognized acLDL, and SR and acLDL-Au conjugates were concentrated in a coated pit 2 min after incubation. The conjugates were then internalized in the endosome 5 min after incubation. A few acLDL-Au conjugates were present in the endosome near the nucleus, but most of them were found in the lysosome 10 min after incubation. SR was found in the Golgi apparatus 15 min after incubation. These results suggest that SR in PAM may play an important role in the removal of alveolar surfactant. 2) FcR: Effects of FcR mediated phagocytosis on O2-release and phagosome-lysosome fusion in the phagosome of PAM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306226 TI - [Induction of tumor cell killing by human alveolar macrophages and its regulation by IL-4]. AB - The present study was undertaken to examine the effects of IL-4 on induction of cytotoxic killer activity and on production of antitumor mediators by human monocytes and alveolar macrophages (AM). The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4. Addition of IL-4 to cultures of AM or monocytes with endotoxin resulted in dose-dependent suppression of their cytotoxic activity against A375 and its variant cells resistant to IL-1 and TNF alpha. IL-4 inhibited the production of IL-1 and TNF-alpha by AM at the protein and mRNA levels. Oxygen radical production was also suppressed by treating AM with IL-4. IL-1 receptor antagonist (IL-1ra) was also produced by monocytes stimulated with LPS, but not with IL-4. Marked up-regulation by IL-4 of IL-1ra production in LPS-stimulated monocytes was observed at both the mRNA and protein levels. These findings suggest that IL-4 may be important in down-regulation of antitumor activation of human monocyte-macrophages, not only directly through inhibition of production of antitumor effector molecules, but also indirectly through up-regulation of production of IL-1ra. PMID- 1306227 TI - [Expression of angiotensin II receptor on BALF macrophages from patients with sarcoidosis and healthy individuals]. AB - We previously reported that angiotensin II (A-II) enhanced the accessory function of BALF macrophages in some patients with sarcoidosis. We hypothesized that this finding was mediated by the A-II receptor on BALF macrophages. From this viewpoint, we investigated the expression of A-II receptor on BALF macrophages. The binding of 125I-A-II to BALF macrophages was specifically inhibited by unlabeled A-II when incubated for 1 hour at 37 degrees C. However, the uptake of 3H-inulin to BALF macrophages was not inhibited by unlabeled inulin under the same conditions. These findings indicate that the binding of 125I-A-II to BALF macrophages was mediated by the putative A-II receptor, and was not due to pinocytosis. PMID- 1306228 TI - [Coronet status of digital radiography in chest medicine]. AB - It has been ten years since Computed Radiography (CR) was introduced to evaluate its efficacy on the diagnosis of chest diseases in Japan. Over 600 CR systems are in their daily clinical use. CR images improve the quality of chest X-ray diagnosis with its enhancement parameters, that is, the digital image's contrast and edge enhancement. In daily clinical work, however, some abnormalities on the images, such as infiltrative shadows and fine miliary shadows, have shown CR imaging to have no superiority in visualization compared to conventional X-ray films. The quality of CR images greatly depends on the reconstruction algorithm. The diagnostic system of CR images using CRT monitor and workstations will be warranted in order to make the CR system the optimal and most useful modality in chest medicine. The CR system is potentially applicable in Picture Archiving and Communication System (PACS). PMID- 1306229 TI - [CT diagnosis of diffuse lung disease]. AB - The first HRCT of the lung was obtained in 1979 in Japan. Since then, CT pathologic correlations have been performed in the major diffuse lung diseases. For this purpose, lung specimens were fixed in the inflated condition, which enables precise stereomicroscopic observations to be performed on sliced lung specimens. The first successful correlation was performed in diffuse panbronchiolitis (DPB), where nodular densities in HRCT were proven to correspond to chronic inflammation in the respiratory bronchioles and their neighboring structures. However, further investigation of the correlations are required in diffuse lung diseases showing ground glass-like densities in CT, since this finding is nonspecific and may occur in both airspace and interstitial lung disease. PMID- 1306230 TI - [Evaluation of mediastinal lymph nodes by computed tomography in lung cancer]. AB - It is important to evaluate hilar and mediastinal lymph node metastasis accurately, since the findings are used to determine the indications for therapies and to estimate the patient's prognosis. Computed tomography (CT) is a useful method for this purpose, but it is known that healthy people may also have lymphadenopathy up to 10 to 15 mm, and metastasis is sometimes observed in lymph nodes less than 10 mm in cases of adenocarcinoma. For this reason, it is necessary to establish an optimal criteria for measured values of lymph nodes on CT images. In this study, we compared the size of mediastinal lymph nodes on CT images and histological findings in 425 lymph nodes of 153 primary lung cancer patients resected in our hospital from 1984 to 1991. Criteria were expressed as possible criteria which can be obtained from ROC analysis with compatibility of sensitivity and specificity, and definite criteria which offer highest efficiency. We analyzed these two criteria by minor axis, major axis, their sum, and their product. As a result, minor axis offered the best criteria. The value of possible criteria was 8.7 mm (sensitivity: 73%, specificity: 70%) and definite criteria was 13 mm (efficiency: 88%) in 425 lymph nodes. Analyzed by histological type, the criteria of epidermoid carcinoma (possible criteria: 9.5 mm, definite criteria: 13 mm) were larger than those of adenocarcinoma (possible criteria: 8.3 mm, definite criteria: 11 mm). Analysed by anatomical region and histological type, the criteria of epidermoid carcinoma varied by with the location of lymph nodes, but those of adenocarcinoma were almost constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306231 TI - [Pulmonary arteriography and bronchial arteriography in pulmonary embolism]. AB - Pulmonary arteriography is the most reliable technique for evaluation of pulmonary embolism and other vascular abnormalities. A definitive diagnosis of pulmonary embolism is made on the basis of direct angiographic signs of emboli of intravascular filling defect and vessel cut-off sign. To obtain these findings, pulmonary arteriography needs to be performed as soon as possible, and in acutely ill patients who are in shock and under consideration for thrombolytic therapy or emergency embolectomy, the study should be performed on an emergency basis. Digital subtraction pulmonary angiography may be an useful technique for massive pulmonary embolism, but it cannot exclude clinically important peripheral pulmonary embolism. Wedged pulmonary arteriography can demonstrate the direct signs of distal emboli, which are difficult to obtain by main pulmonary artery injection angiogram. In the chronic stage of pulmonary embolism, bronchial arteriogram shows collaterals to pulmonary arteries. This study may be useful in patients with chronic pulmonary embolism, especially when thromboembolectomy is planned. PMID- 1306232 TI - [Diagnosis of respiratory system diseases using radio isotopes]. AB - Common respiratory diagnostic imaging techniques using radioisotopes are ventilation-perfusion, perfusion, aerosol inhalation and tumor scintigraphy. The special features of respiratory imaging diagnostic techniques using radioisotopes are the possibility of early detection of disease and the non-invasiveness of the procedure. Also, no patient effort is required. The kinds of isotopes used are as follows: ventilation-perfusion (133Xe, 13N, 99mTc-pseudogas), perfusion (131I, 99mTc), aerosol inhalation (99mTc), tumor (67Ga, 201Tl). The advantages of these procedures are expected to lead to further developments in respiratory examinations using radio isotopes. PMID- 1306234 TI - [MRI of the thorax; clinical application and efficacy in 100 thoracic diseases]. AB - We carried out a retrospective analysis of about 100 surgical cases of mediastinal, pleural, chest wall and pulmonary disorders in order to determine the clinical application and efficacy of MRI (magnetic resonance imaging) of the thorax. Coronal and/or axial image of T1-weighted images were obtained in all cases, and T2-weighted or gadolinium-DTPA contrast-enhanced T1-weighted images were additionally obtained in several selected cases. All MR images were compared with findings of chest X-ray, CT and IVDSA (intravenous digital subtraction angiography) as appropriate. As a result, MR images were considered to provide additional information to that obtained by conventional techniques of chest X-ray and CT, in demonstrating chest wall invasion of pulmonary carcinoma, detecting hilar masses, which were difficult to distinguish from vessels, and in defining mediastinal masses. The anterior segment of the diaphragm is clearly depicted, aiding the differentiation of Morgagni hernia from other entities. Tuberculoma showed peripheral enhancement in Gd-enhanced T1 WI, which was distinctly different from the enhancing pattern of carcinomas. With the use of surface coil, the pleura and chest wall anatomy were clearly demonstrated. It is hoped that the wide application of this technique will increase the diagnostic accuracy of chest wall tumor invasion. PMID- 1306233 TI - [Studies on the regulation of normal bronchial epithelial cell proliferation and proto-oncogene expression]. AB - The regulatory mechanisms of proliferation and differentiation of normal airway epithelial cells seem important for the better understanding of lung carcinogenesis. We isolated bovine and human bronchial epithelial cells by enzymatic digestion of bronchi, and cultured them in serum-free growth factor supplemented medium. To determine the role of growth factors in the proliferation of bovine bronchial epithelial cells, the effect of each of these additives was evaluated. Of these, fetal calf serum (FCS), bovine pituitary extract (BPE), insulin and insulin-like growth factor-1 (IGF-1) showed a significant stimulatory effect on cell growth. These four additives induced transient increases in c-fos, c-jun and c-myc proto-oncogene mRNA levels. Transforming growth factor beta (TGF beta) inhibited growth factor-induced cell proliferation, and also showed selective inhibition of c-myc induction. We also studied the effect of interleukin 6 (IL-6) on human bronchial epithelial cell proliferation. IL-6 showed a significant inhibitory effect on cell growth. These cells were capable of expressing and releasing IL-6 and had specific receptors for IL-6, suggesting an autocrine mechanism. These results suggest that TGF beta and IL-6 may play roles in the regulation of airway epithelial cell growth as inhibitory growth factors. PMID- 1306235 TI - [Application of ultrasonography in chest diseases--usefulness of ultrasonography and physiologic evaluation of low pressure vascular system]. AB - Air and bones, which limit echo penetration to the lesion, are the major components of the thorax. Recently, however, there have been many reports concerning the valid application of ultrasonography for evaluation of chest diseases. In this paper, we report the usefulness of ultrasonography to analyze thoracic lesions based on our experience. Generally, ultrasonography is a method providing high resolution and real-time images. Using these characteristics, we tried to obtain physiological information concerning the hemodynamics of the right heart system. We addressed the results of our studies using ultrasonography as follows; 1) relationship between ventilatory change of IVC and central venous pressure, 2) estimation of pulmonary arterial pressure by measuring the size of the pulmonary artery, 3) dynamic changes of SVC configuration. PMID- 1306236 TI - [Cytogenetic analysis of lung tumors by in situ hybridization with chromosome specific DNA probes]. AB - Fluorescent in situ hybridization (FISH) with biotinated chromosome-specific repetitive DNA probes was used for the cytogenetic study of lung tumors and three cell lines of human lung cancer. The authors utilized a set of satellite DNA probes, specific for chromosomes 7, 17, X, Y in order to detect numerical chromosome aberrations in tumor cell nuclei. Normal diploid human lymphocyte nuclei, which served as the control, have have two signal spots in 95% of nuclei in response to 7, 17 chromosome probes. However, lung cancer cells have numerical heterogeneity, and copy numbers as determined by FISH were not definite with each probe. Discrepancies between cytogenetic and flow cytometric studies in the detection of aneuploidy in some tumors were shown. The number of FISH spots showed a correlation only with the Ki-67 labeling index expressed in proliferating cells. Loss of the Y chromosome in a high percentage of cells was seen by FISH in some tumors from male patients. These data indicate that FISH with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of lung tumors with respect to the detection of numerical chromosome abnormalities. PMID- 1306237 TI - [Analysis of oncogenes and suppressor genes in lung cancer and bronchial lesions from high risk group]. AB - The authors investigated methods for analysis of oncogenes and tumor suppressor genes in lung cancers and bronchial lesions from high risk patients (retired poison gas factory workers). Amplifications of C-, L-, N-myc, length of terminal repeat array (TRA), mutations of p53 gene, p53 mRNA and K-ras genes were analysed in frozen specimens of surgically resected lung cancers. Various lesions including dysplasia, squamous metaplasia, goblet cell metaplasia, and basal cell hyperplasia were detected in the bronchial epithelium of biopsied specimens from retired poison gas factory workers. Analysis of p53 gene and k-ras gene mutations was performed on these formalin fixed, paraffin embedded samples, but no evidence of mutation has been found to date. PMID- 1306238 TI - [Induction of tumor immunity by cytokine cDNA transfected Lewis lung carcinoma]. AB - It is difficult to induce anti-tumor immunity in tumors with low antigenicity. In order to develop a more effective method of immunotherapy, we transfected interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6) genes into Lewis lung carcinoma (LLC) cells. Then, 1 x 10(6) LLC-IL-2, LLC-IL-4 or LLC-IL-6 cells were transplanted into C57BL/6 mice subcutaneously. All mice transplanted with LLC-IL2 and half those with LLC-IL-4 rejected the tumor cells. Survival time of LLC-IL-6 transplanted mice was significantly shorter than that of LLC transplanted mice, with no difference in tumor growth. These data suggest that transplantation of IL-2 or IL-4 gene transfected cells could effectively induce immunity against LLC. IL-6 transfection did not induce immunity, but induced cachexia. PMID- 1306239 TI - [Biochemical and clinical aspects of pulmonary surfactant proteins]. AB - Pulmonary surfactant is a complex mixture of phospholipids and proteins which is synthesized and secreted by alveolar type II cells. Its presence is essential to prevent the collapse of alveoli at the end of expiration. Recently, it has been demonstrated that in addition to its reduction of surface tension of alveolar surfaces, pulmonary surfactant exhibits several other functions in the alveolar lining layer, and surfactant proteins are definitely involved in the expression of these functions. The present study first focused on the recent advances in basic research of hydrophilic surfactant apoproteins, SP-A and SP-D. Both are glycoproteins with C-type lectin structure at the C-terminal region and collagenous structure at the N-terminal half of the proteins. We revealed that SP A binds specifically to dipalmitoylphosphatidylcholine and galactose-ceramide and asialo GM2, while SP-D binds specifically to phosphatidylinositol and glucose ceramide. We discuss the physiologic and metabolic roles of the specific lipid binding with surfactant proteins of the surfactant system. We next studied changes in pulmonary surfactant in respiratory diseases using anti-human SP-A monoclonal antibodies. We demonstrated SP-A immunoglobulin complex in the sera of patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. PMID- 1306240 TI - [The role of muscarinic receptor subtypes in feline tracheal submucosal gland secretion]. AB - To determine what muscarinic receptor subtype regulates the rise of intracellular calcium concentration ([Ca2+]i) and resultant airway submucosal gland secretion on muscarinic receptor stimulation, we examined the effects of atropine (ART), pirenzepine (PZ), 11([2-(diethylamino) methyl-1-piperidinyl] acetyl)-5,11-dihydro 6H-pirido (2,3-b)(1,4)-benzodiazepine-6-one (AF-DX116) and 4-diphenylacetoxy-N methylpiperidine methiodode (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, mucus glycoprotein (MGP) secretion and electrolyte secretion from submucosal glands isolated from feline tracheae. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura2. We determined MGP secretion by measuring trichloroacetic acid (TCA)-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4 DAMP and ATR against MCh (10(-5) M)-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. IC50 values of these antagonists against MCh (10(-5) M)-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10( 9) M and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na-efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M ATR (p < 0.01, respectively), but the inhibitory effect of PZ (10(-7) M) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306241 TI - [Characterization of a receptor for interleukin-5 on pulmonary eosinophils with eosinophilic pneumonia]. AB - Interleukin-5 (IL-5) acts on eosinophil differentiation and activation, suggesting the existence of a membrane receptor for IL-5 on eosinophils. Here, we report that 125I-labeled recombinant human IL-5 bound to high affinity receptors on human eosinophils, especially pulmonary eosinophils in eosinophilic pneumonia obtained bronchoalveolar lavage (BAL). No specific binding occurred on neutrophils, nor on the undifferentiated eosinophilic cell line. EoL-3, in the absence of stimulation. The specific binding of IL-5 was induced by incubation at 37 degrees C of human eosinophils and EoL-3 cells with GM-CSF and with the supernatants of BAL cells from patients with eosinophilic pneumonia. These results indicate the existence of a specific binding site for IL-5 on human eosinophils with variable affinity in eosinophil hypodense or normodense subpopulations, as previously reported for other membrane receptors. Furthermore, lung cells (BAL cells) in patients with eosinophilic pneumonia may be involved in the production certain eosinophilopoietic growth cytokines such as IL-3, GM-CSF and IL-5. PMID- 1306242 TI - [Interleukin 6 receptors on human bronchial epithelial cells]. AB - It has been suggested that a variety of cytokines may play important roles in the regulation of immune and inflammatory responses in the lung. The purpose of this study was to determine whether interleukin 6 (IL-6) could affect the cell growth of human bronchial epithelial cells via a specific receptor for IL-6. Human recombinant IL-6 inhibited the cell proliferation in a dose-dependent manner. Binding assay with radiolabelled IL-6 demonstrated that human bronchial epithelial cells had specific receptors for IL-6. Moreover, Northern blot analysis using digoxigenin-labelled IL-6R mRNA expression in these cells. Interestingly, proinflammatory cytokines IL-1 alpha and IL-6 upregulated IL-6R mRNA levels. These results suggest that IL-6 may affect the functions of bronchial epithelial cells via a specific receptor, and that its activity on cells may be regulated at the level of receptor-cytokine binding. PMID- 1306243 TI - [Functional evaluation of possible cytokine receptors on airway smooth muscle: modification of airway smooth muscle responses by cytokines]. AB - Recently, the role of activated T-cell derived cytokines in the pathophysiology of asthma has been recognized. In this study, we evaluated the effects of interleukin-2 (IL-2) and gamma interferon (IFN-gamma) on contractile and relaxing responses of guinea-pig tracheal strips in isometric tension measurement system. IL-2 enhanced carbachol (Carb)- and KCl-induced contraction, and attenuated isoproterenol (Iso)-induced relaxation. IFN-gamma had little effect on Carb and KCl contraction, but enhanced Iso relaxation. These effects of cytokines were abolished by denuding epithelium from tracheal strips. These results suggest that IL-2 and IFN-gamma are able to affect functions of non-immune cells in the airway, and that the airway epithelium has some role in the effects of cytokines on airway responses. PMID- 1306244 TI - [Diversity of T-cell antigen receptor response in individuals with sarcoidosis]. AB - T-lymphocytes recognize specific antigen(s) through T-cell antigen receptors (TCRs). There are two classes of TCRs: those composed of alpha beta chain dimers and those formed by gamma delta dimers. Although the pathogenesis of sarcoidosis is still unclear, participation of exogenous antigen(s) is highly suggested. To investigate the mechanism of activation and accumulation of T-lymphocytes at the sites of disease, the bias of TCRs in individuals with sarcoidosis was evaluated with respect to several points. Eighteen of 51 cases of sarcoidosis showed increase of gamma delta-TCR positive T-lymphocytes in the blood. In contrast to the blood, a low number of gamma delta T-cells and evidence of T-cell stimulation through alpha beta-TCR were observed in the lung. The TCR junctional regions of V gamma 9, V delta 2 and V beta 8 gene segments were sequenced from blood and lung T-cells of individuals with sarcoidosis and normal subjects, using RT-PCR. In normals, a huge diversity of the junctional region sequences was observed in V gamma 9, V delta 2 and V beta 8 transcripts in the blood and lung. In contrast to normal subjects, a subgroup of sarcoidosis showed an increase of V gamma 9 transcripts sharing identical sequences. Although less marked than for V gamma 9, an increase in identical junctional region sequences was also observed in V delta 2 transcripts. All junctional region sequences of V beta 8 transcripts in the blood and lung were unique, indicating polyclonal activation of T-cells through TCR beta-chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306245 TI - [67kDa-laminin receptor in human lung cancer]. AB - Complimentary DNA for the 67kDa-laminin receptor was cloned from the cDNA library derived from a human lung cancer cell line, and the nucleotide sequence was determined. Expression of the gene was estimated by Northern analysis in various types of human lung cancer. As a result, increased expression of the laminin receptor was demonstrated especially in the cell types of small cell cancer and bronchioloalveolar cell cancer, which are aggressive biologically. Antibody raised against a partial sequence of the polypeptide was prepared for immunodetection of 67kDa-laminin receptor. It was shown that immunohistochemistry with the antibody could be applied to diagnostic use in lung cancer. The results also suggest that the laminin receptor polypeptide is not necessarily a membrane associated protein and may function without further processing to the receptor. PMID- 1306246 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. Nurse teacher should be a role model of clinical nurse]. PMID- 1306248 TI - [Status and awareness of assistant nurse students--student assistant nurses tell their hard working conditions and obligations]. PMID- 1306247 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. How can we make student clinical practice more effective?]. PMID- 1306250 TI - [Medical topics: physicians are helped by patients' will to get well]. PMID- 1306249 TI - [Expectant mothers at my obstetric clinic--maternal love vs. paternal love]. PMID- 1306251 TI - [Getting old and thinking hard--discretion of 60 years old]. PMID- 1306252 TI - [Letter from Alabama--nurses work in expanded role]. PMID- 1306253 TI - [Health administration: retention rate of hospital nursing staff]. PMID- 1306254 TI - [Home care in Denmark--24 hour visiting nurse service]. PMID- 1306256 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. Teacher need more clinical practice for good relationship between education and practice]. PMID- 1306255 TI - [A midwife in Paraguay--nurses in Paraguay]. PMID- 1306257 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. Practice and education still going parallel but trying to come closer]. PMID- 1306259 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. Nurse teachers are unable to help solve problems experienced by clinical instructors]. PMID- 1306258 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. Good communication required for effective clinical practice for students]. PMID- 1306260 TI - [Hospital nursing staff's view of nurse teachers as clinical instructors. Responsibility of clinical instructors in nursing education]. PMID- 1306261 TI - [Expectant mothers at my obstetric clinic--maternity and exercises]. PMID- 1306263 TI - [Medical topics: "why" and "how to" of pain killer administration]. PMID- 1306262 TI - [Getting old and thinking hard--humor in terminal stages of illness]. PMID- 1306264 TI - [A midwife in Paraguay--fortune telling on getting married]. PMID- 1306265 TI - [Health administration: rating of medical fee]. PMID- 1306266 TI - [Image of nurses, nurses' identity, changing society]. PMID- 1306267 TI - [Communication with patients who do not understand Japanese well]. PMID- 1306268 TI - [JNA develops the public health nursing staff standard for local governments]. PMID- 1306269 TI - [Response to Ms. F. Sugitani's article "Crisis of nursing in Japan: quality, quantity and professionalism of nursing are endangered" (Kango, June 1992). Who is going to resolve the nursing shortage?]. PMID- 1306271 TI - [Response to Ms. F. Sugitani's article "Crisis of nursing in Japan: quality, quantity and professionalism of nursing are endangered" (Kango, June 1992. "Crisis" and issues of the assistant nurse system]. PMID- 1306270 TI - [Response to Ms. F. Sugitani's "Crisis of nursing in Japan: quality, quantity and professionalism of nursing are endangered" (Kango, June 1992). Review of nursing/nursing issues as discussed in literature after World War II--evaluation of what we have achieved]. PMID- 1306272 TI - [Response to Ms. F. Sugitani's article "Crisis of nursing in Japan: quality, quantity and professionalism of nursing are endangered" (Kango, June 1992). We are achieving slow but steady progress]. PMID- 1306273 TI - [Response to Ms. F. Sugitani's article "Crisis of nursing in Japan: quality, quantity and professionalism of nursing are endangered" (Kango, June 1992). Quality of current standardized nursing care]. PMID- 1306274 TI - [Response to Ms. F. Sugitani's article "Crisis on nursing in Japan: quality, quantity and professionalism of nursing are endangered" (Kango, June 1992). Gaps between people's expectation of nurses and nursing quality]. PMID- 1306275 TI - [Years of rehabilitation after spinal injury--they encouraged me to come out and enjoy life]. PMID- 1306276 TI - Special medicolegal considerations in pediatric pathology. PMID- 1306277 TI - Perinatal drug and alcohol abuse: rights, laws, and responsibilities. PMID- 1306278 TI - Experts in malpractice litigation--what about nurses? PMID- 1306279 TI - Practice standards: legal implications. PMID- 1306280 TI - Update on AIDS--medical, legal, and societal concerns. PMID- 1306282 TI - Active voluntary euthanasia: medical-legal aspects and their relationship to societal and moral principles. PMID- 1306281 TI - Legal medicine: the auxiliary to bioethics. PMID- 1306283 TI - Sudden, unexpected deaths in adults: clinical-pathological correlations and legal considerations. PMID- 1306284 TI - Bite mark evidence: increasing acceptance with a qualified expert witness. American Board of Forensic Odontology. PMID- 1306285 TI - Relationships between coroners-medical examiners and the news media. PMID- 1306286 TI - Substance abuse in head injury rehabilitation. AB - The desire for relief of discomfort appears to be universal, and the fact that certain chemicals can provide relief from physical/emotional discomforts may understandably result in recourse to them. Various factors may result in these chemicals having deleterious effects, either because of toxicity, addiction, or adverse sociocultural consequences. The widespread use of these chemicals and their manifold effects warrant increasing study and familiarity with patterns of abuse, etiology, and management on the part of all who are involved in the delivery of human services. PMID- 1306287 TI - [The use of the pupillometric gauge by the nurses' aide]. AB - To test the use of the "pupillometer tongue depressor" by auxiliary nursing was the goal of this study. The same evaluation used by nurses was performed in this group. After explaining the use of the device, each auxiliary nursing registered on a "Card-test" the value of the two circles, which diameters were equal or unequal. Afterward, a pair of the auxiliary nursing evaluates the pupil diameter of one patient. The accuracy of the millimeter circles was very high but not the effectiveness of the pupil diameter measurement. Nearly 1/3 of the auxiliary nursing referred difficulties in performing this evaluation. PMID- 1306288 TI - [The use of new dressing resources in the nursing consultation]. AB - The author performed the treatment of infected or non-infected wounds with the association of papain and 2 types of synthetic dressings: activated charcoal cloth dressing and hydrocolloid dressing. Eighteen (18) patients, mean age 58.4 years, were followed during 20 dressings. The treatment period was 2 1/2 months-3 months. The infected wounds were treated with the activated charcoal cloth dressing and the non-infected wounds with the hydrocolloid dressing. The evolution of wound healing until the tenth dressing, (about 1 month of treatment) showed that area initially affected was reduced between 48.6% and 89.7% until the twentieth dressing. PMID- 1306289 TI - [Pain: its occurrence and evolution in the postoperative period of heart and abdominal surgery]. AB - The high incidence and low resolution of the pain after surgery are shown in international literature. During the five days after the cardiac and abdominal surgery, these patients were asked once a day about their pain. Nearly 50% of the patients answers showed pain complaints. At the cardiac patients 47% did not take treatment during the last four hours, although the medicine was prescribed by the doctor to be used in eventual necessity. Similar occurrences happened with abdominal patients where no medicine was given in 68.2% events of their pain complaints. So, we find that the under-identification and undertreatment of the pain are like the other studies. PMID- 1306290 TI - [The telephone interview: the methodological strategy for collecting population data]. AB - The interview by telephone is not an ordinary procedure to obtain investigation data. By knowing that is rarely used in Brazil, the study was planned aiming to: identify the individuals' characteristics who answer the sampled telephones; raise the interviews' statements about the operational technique and evaluate the telephone used as data collection procedure. The data indicate that most of the people who were interviewed, were females, between 30 and 40 years old and housewives. The interviewers considered between 30 and 40 years old and housewives. The interviewers considered the experience interesting, in despite of the difficulty to maintain people talking on the phone. The authors state that the interview by telephone is an efficient and fast way of bringing up data for investigation which aims to raise opinions about certain matters. PMID- 1306291 TI - [Simulation in the teaching of the cardiorespiratory system: a report of innovative experience]. AB - The nurse teachers in charge of the Auxiliary Nursing Course at the Heart Institute (InCor-FMUSP) propose simulation as an innovative teaching strategy and describe its application to the Cardiorespiratory System. By doing this, they make their students participate actively in their classes, thus improving the teaching-learning process. PMID- 1306292 TI - [The systematization of nursing care for the colostomy-ileostomy patient in a private hospital]. AB - A Systematic Nursing care to ostomized patients at Oswaldo Cruz German Hospital (Sao Paulo Brazil) has been used in order to care for these patients through a nursing process approach since December 1988. Until June 1991 the group gave orientation to 115 patients. This systematic nursing care has three steps: pre operative period, pos-operative period and discharge. These steps improved self care without complications and guided the patients to work with ostomy associations which helped them im their whole reintegration. PMID- 1306293 TI - [The profile of nursing teachers in undergraduate courses in greater Sao Paulo]. AB - This paper searches to identify some aspects of the profile of the undergraduate nursing faculty members and to detect the differences and similarities among the group of teachers of public and private schools. A sample of 120 faculty members of five schools was studied in August of 1990 using a questionnaire. The data was analysed according to the following categories: demographic data, social economical status, university stand, professional development and perspectives. The results showed that there are more similarities than differences within this faculty members, once they belong to the an homogeneous social, economical and cultural class with a few exceptions. PMID- 1306294 TI - Expression of Mn-superoxide dismutase in carcinogenesis. AB - Human liver manganese superoxide dismutase (Mn-SOD) was highly purified by a simple procedure and crystallized. A monoclonal antibody against Mn-SOD, whose antigen-binding epitope is a C-terminus peptide was developed. Using this antibody, an enzyme-linked immunosorbent assay (ELISA) was developed. We found that Mn-SOD is highly expressed in human ovarian cancer and the serum level of the enzyme is a useful marker for the diagnosis and monitoring of the epithelial type of ovarian cancer. Tumor necrosis factor-alpha (TNF), lipopolysaccharide, IL 1 and phorbol ester induced the m-RNA of Mn-SOD as well as protein levels in TNF resistant cells. No such induction was observed in Cu, Zn-SOD. Studies on the induction mechanisms indicated that at least two separate signal-transducing pathways are involved in expression of the Mn-SOD gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulations with various cytokines in which a protein factor that can be induced by phorbol ester treatments is involved. PMID- 1306296 TI - DNA repair pathways in mammalian cells analyzed by isolation of ACNU-sensitive Chinese hamster ovary cells. AB - 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) causes chloroethylation of DNA strand followed by cross linking through an ethylene bridge. We recently isolated two ACNU sensitive mutants from mutagenized Chinese hamster ovary cells, and found them to be new drug sensitive recessive mutants (Hata et al. 1991). The O6-methyl guanine DNA methyl transferase (MT) activities of these cells were undetectable as the parental cell line, indicating that the sensitivity of the mutant cell lines to ACNU was not due to the decreased cellular level of this enzyme. By complementation analysis with the 7 established UV-sensitive CHO cell lines, one of the mutants, UVS1, turned out to complement their UV-sensitivity and, therefore, build a new complementation group among all the CHO cell lines ever reported. The other mutant, CNU1 showed hypersensitivity only to chlorethylating agents (ACNU, CCNU) and exhibited a slightly reduced unscheduled DNA synthesis (UDS) induced by UV. It is, therefore, suggestive that this mutant is defective in a specific step of DNA repair systems, which is important for the processing of DNA damages produced by ACNU. Only cell lines from the complementation group 1 and 4 out of 7 established complementation groups of UV-sensitive CHO mutants were more sensitive to ACNU than UVS1 and CNU1, indicating some steps of excision repair pathways as well as specific repair system play important roles in repairing ACNU-induced DNA damages. PMID- 1306295 TI - Role of intestinal microflora in metabolism of glutathione conjugates of 1 nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide. AB - DNA adduct formation in the liver of B6C3F1 mice after administration of 1 nitropyrene (1-NP) was shown by the 32P-postlabeling technique. The major adduct was not N-(deoxyguanosin-8-yl)-1-aminopyrene, which was easily formed in in vitro nitroreduction of 1-NP in the presence of DNA, but the major spots migrated to the same position as the in vitro DNA adduct spots of K-region epoxides of 1-NP (1-NP 4,5- and 9,10-oxide). 1-NP oxides formed by the oxidative activation of 1 NP in the liver were excreted into the bile as detoxified glutathione conjugates which were changed to cysteine conjugates in the upper intestinal tract. The cysteine conjugates were degraded by cysteine conjugate beta-lyase (beta-lyase) of intestinal microflora in the lower intestinal tract. The mutagenicity of cysteine conjugates of 1-NP oxides for Salmonella typhimurium was enhanced by addition of beta-lyase and was decreased by addition of aminooxyacetic acid, a beta-lyase inhibitor. The in vitro binding of the cysteine conjugates to calf thymus DNA was increased by addition of beta-lyase and xanthine oxidase. We administered glutathione conjugates of 1-NP oxides to two groups of mice that had been treated with antibiotics or saline by gavage and analyzed the DNA adducts in the lower intestinal mucosa. The specific DNA adducts were detected in the saline treated group but not in the antibiotics-treated group. These results suggest that intestinal microflora play an important role in activation of glutathione conjugates of 1-NP oxides. PMID- 1306297 TI - Mass screening for neuroblastoma in Miyagi Prefecture. AB - In Japan, aiming at early and preclinical detection of neuroblastoma in infancy a mass screening program for the tumor has been implemented nationwide using urinary tests for catecholamine metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA) (Sawada 1990; Sawada et al. 1991). In this report, the results obtained from the screening program in Miyagi Prefecture for the last 6 years are described. The detection rate of neuroblastoma by mass screening was 1:8,377 among 125,652 infants tested in Miyagi Prefecture. All but one patients survived after removal of the primary tumor and none or minimal chemotherapy. PMID- 1306298 TI - Phosphorylation of the anti-oncogene products and control of the cell cycle. AB - To investigate the function of the RB protein, we have studied cellular RB binding proteins and protein kinases responsible for phosphorylation of the RB protein. (1) We purified a cellular RB-associated protein p56 which competes with SV40 large T antigen for binding to the RB protein. (2) In another experiment, we screened expression libraries of U937 monocytic leukemia cell line by West Western method and obtained two cDNA clones that encode RB binding proteins. (3) The RB protein was found to be phosphorylated by cdk2 and MAP kinase in vitro. Most of the sites phosphorylated in vitro are the same as those phosphorylated in vivo and the time course of activation of cdk2 in the cell cycle were similar to that of phosphorylation of the RB protein. PMID- 1306299 TI - Mutations of the p53 gene and other genes involving in human colorectal carcinogenesis. AB - In this study, structural changes of the p53 gene in primary specimens of human colorectal carcinomas were analyzed by polymerase chain reaction mediated-DNA sequencing method. Point mutations of p53 gene, including an intronic mutation case, were detected in 8 of 14 carcinomas (57%). Point mutations of the gene were also observed in 2 of 2 adenomas, suggesting that mutations occur prior to the carcinoma stage. These results support that p53 gene plays an important role in the development of colorectal cancer. The frequency of Ki-ras oncogene mutations was also studied by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP). This resulted in the rate of 42% (10/24), a quite similar value obtained by other methods. As PCR-SSCP analysis is a convenient method to detect point mutation, we have now examined 24 colorectal cancers for the p53 gene by this method, and detected the mutations. Furthermore, expression of the DCC gene, a candidate of tumor suppressor gene involved in colorectal carcinogenesis, was examined by reverse transcriptase-mediated PCR (RT PCR) assay, resulting in significant reduction on the DCC expression in 8 of 14 carcinoma cases (57%). PMID- 1306300 TI - A novel general strategy for cloning tumor suppressor genes using radiation reduced chromosomal superfragments. AB - To identify the tumor suppressor gene on human chromosome 11p15, we generated mouse microcell hybrids containing small transferable chromosome 11p15 fragments, which we have termed "DNA superfragments". These hybrids will be used to identify which fragments contain a tumor suppressor gene by direct transfer of the fragments to tumor cells via microcell fusion. PMID- 1306301 TI - Fos and Jun: oncogenic transcription factors. AB - The fos and jun proto-oncogenes are members of the set of genes known as cellular immediate-early genes. Their expression is induced transiently by a great variety of extracellular stimuli associated with mitogenesis, differentiation processes or depolarization of neurons. They encode DNA binding proteins that form dimeric complexes through a leucine zipper structure that function as transcription factors. Continuous overexpression of fos or jun causes transformation of fibroblasts. Because of their ubiquitous expression it is believed that the target genes regulated by Fos and Jun are different in the many circumstances in which they are expressed. Thus, their functional specificity is likely to be regulated at several levels. We have uncovered several potential mechanisms that could contribute to their regulation. These include formation of a large number of heterodimeric complexes, post-translational modification by phosphorylation and a novel reduction/oxidation (redox) mechanism, presence of both positive and negative transcriptional domains and the ability of Fos and Jun to induce distinct bends in DNA structure. PMID- 1306302 TI - Complex regulation of a tumor marker expression. Enhancer and silencer of the GST P gene. AB - Glutathione transferase P (GST-P) is expressed at high levels in precancerous lesions and hepatocellular carcinomas from a very early stage of chemically induced hepatocarcinogenesis in the rat. To explore the molecular mechanisms of its specific activation, we are investigating the regulation mechanisms of the GST-P gene expression. By using gene technology, we have identified a strong enhancer, GPEI, at 2.5 Kb and a silencer region at about 400 bp upstream from the transcription start site. GPEI has a palindromic structure composed of two TPA responsive element (TRE)-like sequences and binds at least three proteins including AP-1 (c-jun/c-fos). The silencer is composed of several sequences resembling each other and binds at least three proteins including SF-B/LAP/LIP. To determine whether the GST-P gene is activated together with a putative hepato oncogene because they are located close to each other (cis-mechanism), or because they share a trans-acting factor that can activate both genes simultaneously (trans-mechanism), transgenic rats were produced with GST-P control region connected to the CAT reporter. The results unequivocally demonstrate that GST-P gene is activated position-independently by a trans-mechanism. PMID- 1306303 TI - Transcriptional control by myb oncogene product. AB - Structure and function of two domains of c-Myb were analyzed. We show that a leucine zipper structure is a component of the negative regulatory domain, because its disruption markedly increases both the transactivating and transforming capacities of c-Myb. Our results suggest that an inhibitor which suppresses transactivation binds to c-Myb through the leucine zipper, and that c Myb can be oncogenically activated by mis-sense mutation. We also proposed a model, the "tryptophan cluster", for the structure of the Myb DNA-binding domain, in which the three tryptophans form a cluster in the hydrophobic core in each repeat. The results of NMR analysis of repeat 3 revealed that the conserved tryptophans play a key role to make the hydrophobic core. PMID- 1306305 TI - Role of c-Myc on erythroid differentiation. AB - In the early event of the induction of mouse erythroleukemia (MEL) cell differentiation, c-myc mRNA levels show a biphasic change. The elevated expression of a transfected c-myc gene inhibits the commitment and differentiation of MEL cell transformants. In the present work, we have introduced human c-myc mutants into MEL cells under the inducible promoter to define the functional domains of c-Myc involved in erythroid differentiation. The c-Myc domains necessary for commitment and differentiation are not colocalized; almost entire regions are required for inhibition of commitment, whereas domains II and IV that are essential for co-transforming activity with ras are required for inhibition of differentiation. Interestingly, mutants that delete domains for c-Myc dimerization motifs enhanced differentiation. Thus, c-Myc interferes with MEL cell differentiation by interacting with c-Myc partners and the induced protein(s) through dimerization domains. These results suggest that c-Myc may regulate commitment and differentiation by interacting with proteins through different domains. PMID- 1306304 TI - Regulation of Myc: Max complex formation and its potential role in cell proliferation. AB - The myc family of proto-oncogenes encodes short-lived nuclear phosphoproteins (Myc) involved in the control of cell proliferation and differentiation. Here we discuss the evidence for Myc's involvement in normal and abnormal cell proliferation and review recent information on Max, a novel protein that forms a sequence-specific DNA-binding complex with Myc. The properties of the Myc: Max heterodimeric complex suggest a model for how Myc may function in the cell. PMID- 1306306 TI - Functional role of glycosphingolipids in tumor progression. AB - Molecular modeling of glycosphingolipids (GSLs), and their organization in membranes, suggest that GSL "patches" provide binding sites for interaction with ligands and adjacent cells, and that GSLs or their catabolites modulate transmembrane signaling. Aberrant GSL expression is a ubiquitous phenotype common to essentially all types of tumors, and leads to (i) formation of tumor associated antigens defined by a large variety of monoclonal anti-bodies; (ii) aberrant adhesion favoring metastasis and invasiveness of tumor cells; and (iii) aberrant catabolism leading to altered transmembrane signaling and loss of growth control. Classical immunotherapy is based on (i). New approaches termed "antiadhesion" and "anti-signaling" therapy, based on (ii) and (iii), are hereby proposed. PMID- 1306307 TI - Multiple forms of mammalian sialidase: altered expression in carcinogenesis. AB - We have demonstrated that rat liver contains at least four types of sialidase differing in subcellular location, in catalytic property and immunologically. They are intralysosomal, cytosolic and membrane-associated sialidases I and II. Membrane sialidase I locates mainly in plasma membrane and sialidase II in lysosomal membrane. Immunological study reveals that the same types of sialidase exist in various tissues of rat and of other mammalian species. Based on these results, we examined the sialidases in rat hepatomas and in transformed cells of JB6 mouse epidermal cell. Hepatomas were found to possess four types of sialidase and the three of them altered quantitatively. Intralysosomal sialidase activity was higher but cytosolic and lysosomal membrane sialidase activities were lower in hepatomas than in control liver. When the sialidases of transformants of JB6 cells were compared with those of control cells, the activities of two lysosomal sialidases were decreased and contrarily plasma membrane sialidase was increased. We discussed a possible significance of the sialidase alterations in carcinogenesis. PMID- 1306308 TI - The IL-2/IL-2 receptor system: involvement of a novel receptor subunit, gamma chain, in growth signal transduction. AB - We previously demonstrated the existence of a third component, p64, of IL-2 receptor (IL-2R), tentatively named the gamma chain of IL-2R. Our recent studies provided evidence suggesting that the gamma chain endows the beta chain of IL-2R with IL-2 binding ability. The gamma chain was detected in lymphoid transfectants of IL-2R beta cDNA, which showed the intermediate-affinity IL-2R, but not in nonlymphoid transfectants of IL-2R beta cDNA, which showed no IL-2 binding activity. The comparative study between two subclones of lymphoid MOLT4 transfectant of IL-2R beta cDNA demonstrated that the amount of the gamma chain coprecipitated with IL-2R beta was proportional to numbers of the IL-2 binding sites. These results suggest the possibility that the gamma chain associates with IL-2R beta and has an important role in formation of the intermediate-affinity IL 2R complex. On the other hand, we have also demonstrated the association of IL-2R beta with a certain tyrosine kinase, of which activation by IL-2 could be indispensable process at the initial pathway of signal transduction. PMID- 1306309 TI - The molecular biology of lung cancer. AB - Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non small cell (NSCLC) types. The number of changes has been estimated to be in double digits. These changes include activation of dominant oncogenes myc family, (K-ras and neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and RB as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, such studies have not been performed to date. Documentation of molecular changes in premalignant lesions and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials. PMID- 1306310 TI - Development of the human colonic adenocarcinoma from adenoma as a histopathologically continuous process. AB - The adenocarcinoma sequence of the human colon is usually divided into three separate steps according to the grade of epithelial dysplasia, i.e., adenomas with mild, moderate and severe dysplasia. In an attempt to re-examine whether or not this sequence can be morphologically separable as usually assumed, a total of 192 epithelial lesions including adenomas with various grades of dysplasia were analyzed, relying on morphometrical and multivariate-statistical techniques. Histologic features of epithelial lesions were characterized by 10 quantitative parameters and subjected to 10-variate cluster analysis. In the result of computations, separation of neoplastic lesions into different groups proved to be rather ambiguous, not justifying the classification into three groups as generally expected. It was concluded that adenocarcinoma can develop from adenoma as a seemingly continuous process which may involve more steps than usually assumed. PMID- 1306311 TI - Overexpression and amplification of alpha-PDGF receptor gene lacking exons coding for a portion of the extracellular region in a malignant glioma. AB - Overexpression of the alpha-Platelet Derived Growth Factor Receptor (alpha-PDGF) gene was detected in a case of malignant glioma. This overexpression was accompanied with amplification of rearranged alpha-PDGF receptor gene. We have isolated a cDNA for the transcript derived from the amplified receptor gene. Characterization of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in the extracellular region of the receptor. This in-frame deletion removed a part of the immunoglobulin-like domains in the extracellular region of the receptor. Analysis of the amplified alpha-PDGF receptor gene in the glioma indicated that exons coding for the 81 amino acids were lost by a gene deletion. The gene amplification was also detected in macroscopically normal cortex adjacent to the glioma from the same patient. However, the amplified gene in the macroscopically normal cortex had no major gene rearrangement. These data suggest that the overproduction of structurally altered alpha-PDGF receptor may take part in the onset and the development of malignant glioma. PMID- 1306312 TI - A Ca(2+)-independent protein kinase C, nPKC eta: its structure, distribution and possible function. AB - Protein kinase C consists of a protein family which can be classified into two major groups: Ca(2+)-dependent conventional protein kinase C and Ca(2+) independent novel protein kinase C (nPKC). Among eight known members of protein kinase C family, we found that nPKC eta (eta) isolated from cDNA library of mouse skin, is most abundant in epithelial tissues including skin and epithelia of digestive and respiratory tracts. These data suggest potential role of this isoform in growth, differentiation and carcinogenesis of epithelial tissues. PMID- 1306313 TI - A novel steroidogenic role of suramin-blocked luteal cell growth factors. AB - Growth factors synthesized in the ovarian corpus luteum (CL) have been implicated in the development of the CL. One of these growth factors is basic fibroblast growth factor which acts on luteal cells in an autocrine manner (Tamura et al. 1991; Asakai et al. 1992). To elucidate effects of these growth factors in the development of the CL, we cultured immature luteal cells with defined medium for a week in the presence or absence of a growth factor inhibitor, and measured progesterone in the medium as an indicator of cell differentiation. Culture of luteal cells showed an increased amount of progesterone for three days and continued to synthesize progesterone for at least another four days without serum and pituitary hormones. The addition of suramin, previously reported to inhibit autocrine growth stimulation, accelerate the daily progesterone production of luteal cells apparently by switching on the early onset of differentiation. Suramin also induced apoptosis of the cells after the 3rd day of culture. These data suggest that an autostimulation mechanism by growth factors plays a physiological role on normal cell differentiation, and it is not limited to neoplastic transformation. PMID- 1306314 TI - Flow cytometric DNA analysis of lung cancer cell lines. AB - Tumor DNA content (ploidy) was analyzed by use of flow cytometry (FCM) in 17 lung cancer cell lines which were subcultured in our laboratory. The study included 6 adenocarcinomas, 2 squamous cell carcinomas, 1 adenosquamous cell carcinoma, 5 large cell carcinomas, and 3 small cell carcinomas. Of the 17 lung carcinoma cell lines, 15 revealed aneuploid patterns with DNA index above 1.1, whereas one had diploid. The mean DNA index (DI) in adenocarcinoma, was 1.34 +/- 0.09, DI 1.6, in squamous cell carcinoma, DI 1.0 in adenosquamous cell carcinoma, DI 1.70 +/- 0.66 in large cell carcinoma, and DI 1.29 in small cell carcinoma. Of the 17 cell lines, three lines showed multiploid patterns with clinically poor prognosis and indicated heterogeneity. Flow cytometric DNA analysis using lung cancer cell lines could provide further basic study of lung cancer cells and give a useful information on the degree of the malignancy clinically. PMID- 1306315 TI - Cell kinetic study of murine jejunal crypts during multiple doses per day. AB - We studied cell kinetics of mouse jejunal crypts during multiple fractionation using double labeling methods. Mice were irradiated to the total body once a day or twice a day. Fraction size was 2 Gy. Overall time was 1, 3 and 5 days. Labeling index (LI), duration of S phase (Ts) and potential doubling time (Tpot) were assessed next morning following the irradiation schedule. Mice were administered both bromo-deoxyuridine (BrdUrd) and 3H-Thymidine ([3H]dT) with a constant interval. Removed jejunum were stained with immuno-histochemistry and, then, processed for autoradiography. BrdUrd and [3H]dT LIs were the same and were increased up to 5 days despite the fractionation schedule. After 1 day following 2 fx/day, both Ts and Tpot decreased significantly. For 1 fx/day treatment, neither Tpot nor Ts changed. After 5 day following 1 and 2 fx/day, both Ts and Tpots were the same and Tpots were significantly shorter than that obtained from control. It seems that proliferative responses between 1 and 2 fx/day were different. PMID- 1306316 TI - N-(F-18)-fluoroacetyl-D-glucosamine: a new positron labeled pharmaceutical for cancer study. AB - In order to evaluate the role of hexosamine metabolism in tumor tissue, we studied the biodistribution of N-(F-18)-fluoroacetyl-D-glucosamine (FAGlu) in male Donryu rats bearing poorly differentiated hepatomas (AH109A and AH272). Compare with the former result of the high tumor uptake of FAGlu in C3H/He mice bearing well differentiated spontaneous hepatoma, the tumor uptakes of FAGlu in these tumors showed the lower values. This suggested that spontaneous hepatoma maintained a high activity of glucosamine metabolism, while poorly differentiated hepatoma had little activity. Metabolism of glucosamine in tumor tissue may be another marker for characterizing tumors. We also discuss the tissue distribution of new F-18 labeled hexosamines, N-(F-18)-fluoroacetyl-D-mannosamine and N-(F-18) fluoroacetyl-D-galactosamine in tumor bearing rats. PMID- 1306317 TI - New strategies to establish human monoclonal antibodies. AB - In order to establish human monoclonal antibodies to any sort of antigens efficiently, we have made following two approaches. Our first approach is to improve cell fusion frequency. By improving our previous method for production of human hybridomas, we obtained higher frequency (1/700 vs. 1/5500) compared with our previous method by adding irradiated myeloma cells to culture of fusion cells and modifying the selective medium. Our second approach is to use a SCID-hu mouse for immunization. Since the injection of human PBL can result in the stable long term reconstitution of a human immune system in SCID mouse, we tried to immune SCID-hu mouse with KLH. In the serum of immunized SCID-hu mouse, we obtained human IgG antibodies to KLH. Additionally, we succeeded in establishing human B lymphoblastoid cell lines which produced antibodies specific to KLH. These methods will open new prospects for the detection and therapy of cancer. PMID- 1306319 TI - Marrow transplantation in cancer therapy. AB - Issues in bone marrow transplantation were addressed. Reconstitution of hematopoietic function is achieved by autologous, syngeneic, or allogeneic bone marrow transplant. Problems related to transplants from HLA mismatched family members, and HLA matched unrelated donors were also delineated. PMID- 1306318 TI - Diagnostic use of anti-modified nucleoside monoclonal antibody. AB - By use of monoclonal antibodies (MoAbs) termed APU-6 and AMA-2, we determined the usefulness of urinary modified nucleosides, pseudouridine and 1-methyladenosine, as markers for malignancy. In patients with leukemia and other forms of cancer, these nucleosides elevated significantly and reflected the disease status of patients. The immunohistochemical analysis showed that cancer cells were specifically stained with the MoAbs. Chemical identification of the cellular components reactive with the MoAbs revealed that APU-6-associated antigens were mainly rRNA and AMA-2-associated antigens were mainly tRNA. These results suggest that APU-6 and AMA-2 would be useful tools for clinical and biological studies of cancer. PMID- 1306320 TI - Selective anti-gene therapy for cancer: principles and prospects. AB - Oligodeoxynucleotides can act as antisense complements to target sense sequences of natural mRNAs to selectively regulate gene expression by translation arrest. This is a form of interventional gene therapy. Chemically modified analogs that are nuclease-resistant enable this strategy to be utilized in practice. Of the chemically modified backbone analogs of oligodeoxynucleotides we have used the phosphorothioate (PS) analog, in which a non-bridging phosphate oxygen atom is substituted with a sulfur atom. We have shown that these oligodeoxynucleotide analogs inhibit beta-globin expression in cell free systems, and that they are taken up by cells. Specific sequences have been shown to selectively regulate viral and cellular gene expression, for example the bcl-2 oncogene that is found in ca. 90% of lymphomas. However, the PS analog has certain disadvantages, notably reduced hybridization and non-selective inhibition of translation. We have therefore synthesized a series of (PS-PO) co-polymers and characterized their properties. Other related approaches include catalytic ribozymes, and formation of triplexes by direct interaction of oligomers in the major groove of DNA. In general, a chemically modified oligodeoxynucleotide analog can be regarded as a novel form of informational drug. PMID- 1306321 TI - Basic approach to application of liposomes for cancer chemotherapy. AB - The method for augmentation of systemic in vivo anticancer effect of liposomes (Lip) containing adriamycin (ADM) and endocytosis activity of cancer cells to liposomal preparations have been studied. Encapsulation of ADM in liposomes increases its maximal tolerated dose and pretreatment of animals bearing tumor with tumor necrosis factor alpha (TNF) resulted in effective targeting of ADM-Lip to tumor, leading to its augmented therapeutic effect, but only when TNF and ADM Lip were administered with an appropriate interval. All human tumor cell lines tested showed endocytosis activity to liposomes but the activity was differed among different tumor cell lines. PMID- 1306322 TI - Monoclonal antibody-drug conjugate therapy for the patients with colorectal cancer. AB - Monoclonal antibody drug conjugate A7 was prepared from a mouse splenocyte immunized against human colon cancer. A7 reacted with 80 percent of colorectal cancer and pancreatic cancer. A7 was bound covalently to neocarzinostatin (NCS) to form A7-NCS. A7-NCS had strong cytotoxic activity in vivo and in vitro study. A total of 77 patients with colorectal cancer, including the patients with liver, lung and peritoneal metastasis, were treated with A7-NCS. There were some tumor reduction of liver metastasis on CT scan and pain relief. Follow up study of colorectal cancer patients treated with monoclonal antibody drug conjugate A7-NCS was carried out, with comparing to those treated conventional chemotherapy. Survival rate of the patients with postoperative liver metastasis treated with A7 NCS was slightly higher than that of the patients treated with conventional intraarterial infusion chemotherapy. There was no difference between the group treated with A7-NCS and that treated with conventional chemotherapy in the overall postoperative survival. Patients given a higher dose of the conjugate had a higher survival rate. There were no serious adverse effects in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all A7-NCS treated patients. PMID- 1306323 TI - Characterization and the clinical application of cultured human pulmonary carcinoma cells. AB - We had developed a new method for the selective cultivation of cancer cells in short-term. As a result of these improvement in the culture technique, long-term subcultures of cancer cells are possible in about 80% of cases of small cell carcinoma of the lung and nearly 40% of cases of non-small cell carcinoma of the lung. 23 small cell lung carcinoma (SCLC) cell lines, 48 non-SCLC cell lines and 4 metastatic lung tumor cell lines were established in our institute using the culture method. Fractional culture of cells exhibiting the same growth pattern in primary culture produce several subtype cell lines, which can be used in experimental studies of the heterogeneity of lung cancer and in treatment of patients with lung cancer. Using subcultured cancer cells of the second or third generation, we have developed and have clinically utilized a simple sensitivity test with a Terasaki's microplate for anticancer drugs. In 15 surgical patients with SCLC treated between April 1982 and March 1985, the sensitivity test was used to select optimal anticancer drugs for postoperative chemotherapy. The routine use of the sensitivity test in selecting postoperative chemotherapy definitely improved the 3-year survival rate from 38% to 52%. PMID- 1306324 TI - Control of growth and differentiation of Philadelphia chromosome-positive leukemia cells by tyrosine kinase inhibitors. AB - Herbimycin A, a selective inhibitor of tyrosine kinase activity, induced differentiation of leukemia cells isolated from Philadelphia chromosome-positive chronic myelogenous leukemia patients. However, it did not induce differentiation of leukemia cells from acute myelogenous leukemia patients, although these cells could be induced to differentiate by treatment with appropriate compounds. A selective inhibitor of tyrosine kinase might be useful in chemotherapy of Philadelphia chromosome-positive leukemia. PMID- 1306325 TI - Protein kinase C activity in human leukemia cell lines with reference to sensitivity to antineoplastic agents. AB - Protein kinase C (PKC) regulates many cellular processes. In view of its possible relevance to the drug resistance, the levels of PKC activity were assessed in human leukemia cell lines with reference to the sensitivity to antineoplastic agents. K562/ADM exhibited approximately 2-fold higher levels of PKC activity as compared with the parental K562. After a 1-hr preincubation with Adriamycin (ADM) (0.5, 1, 10 microM), PKC activity in K562 tended to increase dose-dependently, while no substantial alteration was found in K562/ADM. Cisplatin (CDDP) or etoposide was of no effect. The activity in THP-1/E was slightly lower than THP 1, and the basal level stayed unchanged with any one of the above drugs. These results suggest that in K562 increase in PKC activity with ADM may play a role in the process of acquisition of resistance. PMID- 1306327 TI - The difference in immunological properties between lymph node metastatic and non metastatic cell lines of MCA-induced fibrosarcoma of C4W mice. AB - To pursue the process of lymph node metastasis, i.e, the preferential tumor growth in lymph node, we have established the non-metastatic M2B cell line which was derived from 3-methylcholanthrene-induced fibrosarcoma of C4W mouse and a metastatic cell line, M2BLN-M+ which was obtained from metastatic lymph nodes of irradiated C4W mouse which was subcutaneously implanted with cultured tumor cells, because implanted tumor cells were derived from the spontaneous metastatic lymph node of the parental M2B tumor, but regressed in naive C4W mouse. We examined the characteristics of both tumor cell lines in terms of the immunological cellular interactions. M2BLN-M+ showed unexpectedly to be more susceptible to cytotoxicity of immune effectors (NK cell, macrophage and cytotoxic T lymphocyte) than M2B did. When cultured both tumor cells with these effector cells, the growth inhibition of M2BLN-M+ was greater than that of M2B. The regional lymph node of tumor-bearer, however, showed no effective cytotoxic activity as reported by others. On the contrary, when cultured both tumor cells with non-immune lymph node cells, to be surprised, the proliferation of M2B was markedly suppressed, while that of M2BLN-M+ was slightly inhibited. The lymph node cells of M2B-bearing mice showed stronger cytostatic activity to M2B. The results suggest that the cytostatic activity of lymph node cells will be a pivotal factor, concerning the establishment of lymph node metastasis. PMID- 1306326 TI - Tumor localization and biodistribution with radiolabeled monoclonal antibody against pancreatic cancer in tumor-bearing nude mice. AB - Nd2 is a murine monoclonal antibody produced against a mucin fraction purified from xenografts of a human pancreatic cancer cell line SW1990. Immunoperoxidase staining showed that the antigen recognized by Nd2 was present in 82.9% of pancreatic cancer tissues but not in tissues of normal pancreas and chronic pancreatitis. However Nd2 antigen was found not to be elevated in the sera of patients with pancreatic cancer. Four days after injection of 111In-Nd2 into athymic nude mice bearing SW1990 xenograft there was a higher accumulation in the tumor compared to 111In-normal mouse IgG1. When these mice were scanned with a gamma camera, labeled Nd2 was shown to accumulate in the tumor rapidly on the 1st day after injection and by the 4th day tumor accumulation was more distinctly visualized than non-specific accumulation in liver. These results indicate that Nd2 has high specificity and reactivity for pancreatic cancer and may have possible applicants in radioimmunodetection or targeting of therapeutic drugs in pancreatic cancer. PMID- 1306328 TI - Augmented accumulation of transferred lymphokine-activated killer (LAK) cells at murine tumor sites through production of LAK-attractant facilitated by chemotherapy. AB - We observed that effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells on BMT-11, a fibrosarcoma in C57BL/6 mice were improved by combination with cyclophosphamide (CY)-chemotherapy corresponding to enhanced accumulation at tumor sites of LAK cells. On the other hand, cytotoxic T lymphocytes (CTLs) which were able to accumulate at tumor sites more densely than LAK cells produced significant therapeutic effects by themselves. We have also found observed that LAK-attractant activity was detected in conditioned medium (CM) of CY-treated tumor tissue but not in the CM of untreated tumor tissue. These findings reveal that CY-chemotherapy facilitates LAK-attractant-production and enhances the accumulation in tumor tissue of LAK cells and that therapeutic effects of adoptive transfer of LAK cells are augmented by cancer chemotherapy through the enhanced accumulation of LAK cells. PMID- 1306329 TI - The role of complement receptors in tumor cell destruction. AB - Murine peritoneal macrophages exuding early after stimulation with the activators of the alternative complement pathway are able to destroy some of the tumor cells. This destruction is inhibited by anti-Mac-1 and anti-C3. The tumor cell killing needs longer incubation time (> 15 hr), and anti-Mac-1 affects the reaction even if it were put into the reaction mixture at later time of incubation. The results suggest that complement produced by macrophage is deposited onto target cells, and the complement binding targets interact with macrophages through the complement receptor type 3 (CR3), which leads to the cell destruction. It is known that fully activated macrophages kill the tumor cells with the aid of antibody (ADCC) or lectin, but we show here another route of tumor cell destruction, that is, some sort of incompletely activated macrophages can kill some type of tumor cells in cooperation with endogenous complement and complement receptors (CR3) without participation of antibody. PMID- 1306330 TI - Antitumor activity of new antitumor substance, polyoxomolybdate, against several human cancers in athymic nude mice. AB - Antitumor polyoxomolybdates have been recognized in the course of study on the medical utilization of polyoxometalates, inorganic polymers of metal oxide. [NH3Pri]6[Mo7O24].3H2O (PM-8) was found as a representative of antitumor polyoxomolybdates. The growth suppressions of PM-8 against Co-4 human colon cancer xenografted under the subrenal capsule in cd-1 mice were equal or superior to that of 5-FU, MMC, ACNU, ADM and CDDP. Potent antitumor activity of PM-8 is also established against MX-1 human breast and OAT human lung cancer xenografted in athymic nude mice. Polyoxomolybdate is a new type of antitumor substance. PMID- 1306331 TI - Which postoperative combined therapy results in the best prognosis: radiochemocytokine therapy or aggressive chemotherapy? AB - The recurrence of esophageal cancer involving regional nodes, even in patients who have undergone curative surgery, often takes place within three years after surgery. Thus, a new multidisciplinary treatment including cytokines or aggressive chemotherapy with active nutritional support to improve the prognosis in cancer of the thoracic esophagus has been adopted. PMID- 1306332 TI - Tumor radiotherapy monitoring with radioscintigraphy tracers: a comparative study with multiple-tracer technique. AB - A comparative multiple-tracer study was performed to assess the tracer feasibility of monitoring tumor radiotherapy. Metabolic tracers for glucose, amino acid, nucleic acid metabolism: F-18-FDG, C-14-Met, H-3-Thd, and F-18-FdUrd and conventional Ga-67 were compared in the same AH109A radiotherapy model using a new quadruple-tracer technique. F-18-FDG showed a large uptake change and a steady response to radiotherapy which is similar to Ga-67. F-18-FdUrd showed a rapid decrease, but the range of change in uptake was narrow. H-3-Thd and C-14 Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that if labeled with C-11, they may be feasible for PET study. PMID- 1306333 TI - Impacts of the evolutionary concepts of cancer on the study of human diseases. AB - Evolutionary concepts of cancer (Okuyama and Mishina 1984; 1990) have already been found useful in understanding carcinogenesis and anti-cancer defense lines in the body and various cancer attributes. The concept of endosymbiotic disorders gave an impact upon the science of internal medicine leading to discovery of amitosis in Reed-Sternberg cells, a primitive eukaryotism (Okuyama 1991a). A novel concept of vasogenic necrosis was also developed for such diseases of Perthes' disease, cerebral vascular diseases and myocardial infarction: costs of bipedalitic evolution in man. PMID- 1306334 TI - Analysis of human cytochrome P450 catalytic activities and expression. AB - Cytochromes P450 are a large group of membrane-associated heme protein monooxygenases, most of which are responsible for metabolizing foreign compounds. Chemical carcinogens, which are ingested or absorbed into the body as inert forms, are metabolically activated by P450s to electrophilic metabolites capable of binding to and mutating DNA. Different P450 forms are responsible for activation of the various classes of chemical carcinogens including the arylamines, polycyclic aromatic hydrocarbons, nitrosamines and aflatoxins. Thus, the cellular constituency and levels of P450s could determine the fate of a particular carcinogen and the risk of humans to exposure. To study the catalytic activities of human P450s, human P450 cDNAs were cloned and expressed into active enzymes using cultured cells. By both transient and stable cDNA expression systems, several human P450s were found to be capable of metabolically-activating the human hepatocarcinogen aflatoxin B1. These cDNA expression systems can also be used to determine whether an unknown chemical will be activated by a human P450 and thus be toxic or mutagenic in humans. To assess the extent of interindividual variation in P450 expression, probes developed from P450 cDNAs are being used to quantify levels of P450 mRNAs in various human tissues. Studies using RNase protection revealed that the closely related CYP2B6 and CYP2B7 mRNAs could be independently quantified in liver and lung, respectively. This procedure can be used to examine expression of different P450 genes in banks of human tissue specimens. PMID- 1306335 TI - Molecular genetics of the human cytochrome P450-dependent monooxygenases. AB - In this work, the role of genetic as well as environmental factors in determining cytochrome P450 isozyme levels in man have been studied. Simple DNA based assays for the identification of individuals nulled at the CYP2D6 locus are described and have been applied to investigate whether this gene defect is associated with altered cancer susceptibility. In contrast to literature reports, in no cancer type were poor metabolizers underrepresented, indeed in several cancers the mutant allele frequency was increased. A model using human tumours grown as xenografts is described that should help elucidate the factors which regulate P450 levels in man. PMID- 1306336 TI - Human fetal liver cytochrome P-450: capacity to form genotoxic metabolites. AB - Unlike most experimental animals, human fetal liver possesses forms of cytochrome P-450. Thus, the purpose of this study was to clarify the toxicological significance of these forms of cytochrome P-450 to understand possible roles of these cytochromes in producing genotoxic metabolites from promutagens. In fact, human fetal livers showed considerable capacity to activate aflatoxin B1 and IQ (2-amino-3-methylimidazo [4,5-f] quinoline). Three of four forms of cytochrome P 450, P-450HFLa-d, which we could purify from human fetal livers were capable of activating promutagens to mutagens. One of these three forms, namely P-450HFLa, catalyzed the metabolic activation of aflatoxin B1 and IQ. An expression plasmid containing HFL33 cDNA encoding P-450HFLa was constructed and the protein expressed in insect (Sf9) cells and in human cancer cells, MCF-7. Aflatoxin B1 was efficiently activated to a mutagen upon addition of the lysate of Sf9 cells to the incubation mixture for the assay. Transformants of MCF-7 cells expressing P-450IIIA7 (HFLa) showed higher sensitivity to aflatoxin B1 than the parental MCF 7 cells as detected by cytotoxicity. PMID- 1306337 TI - Specific expression of glutathione S-transferase Pi forms in (pre)neoplastic tissues: their properties and functions. AB - The detection of preneoplastic cells is very important for the analysis of carcinogenic processes and for developing strategies for prevention and treatment of cancer. We have been investigating enzyme alterations occurring during rat chemical hepatocarcinogenesis, especially to find more specific enzyme markers for preneoplastic hepatic lesions. We identified the placental form of glutathione S-transferase (GST-P; GST 7-7) as a new marker enzyme for preneoplastic hepatocytes. We also found human placental form, GST-pi, to be a possible tumor marker for various human tissues except liver. In this article, their properties and possible functions are reviewed on basis of our recent investigations. A peroxisomal enzyme, enoyl CoA hydratase, in also described as a possible negative marker for rat preneoplastic hepatic foci/nodules and hepatomas induced by peroxisome proliferators. PMID- 1306338 TI - Congenital hypothyroidism in Turkey: a retrospective evaluation of 1000 cases. AB - In this retrospective investigation, 1000 cases of congenital hypothyroidism followed-up in the Pediatric Endocrinology Unit at Hacettepe University Children's Hospital between 1964-1989 were evaluated with respect to age at diagnosis, main complaints, symptoms and physical findings. The mean age at diagnosis was 49.22 months, with 55.4 percent of patients diagnosed after two years of age and only 3.1 percent during the neonatal period. The main complaints of the patients were growth failure (26.7%), inability to speak (21.4%), and inability to walk (18.1%). The physical signs and symptoms most commonly detected by the physician were hypotonia (72%), constipation (66.8%), cretinoid face (64.6%), and macroglossia (64.6%). These results emphasize the necessity for routine neonatal screening programs to be established in Turkey, with the aim of detecting congenital hypothyroidism. PMID- 1306339 TI - Effects of intravenous immunoglobulin on clinical and immunological findings of patients with humoral immunodeficiency diseases. AB - We evaluated nine patients with humoral immunodeficiency (6 immunodeficiency with hyper-IgM, 2 X-linked agammaglobulinemia, 1 common variable immunodeficiency) who were being treated with intravenous immunoglobulins (IVIG). After the use of the IVIG regimen in a dose of 250-300 mg/kg/4 weeks for one year, the severity and frequency of infections, even in patients with chronic lung disease, decreased significantly. An improvement in pulmonary function tests was observed in four patients who had airway obstruction prior to IVIG therapy. Side effects such as chills and fever were observed in 21 of 91 infusions, particularly in the early months of therapy. Preinfusion administration of aspirin and diphenhydramine prevented these side effects. The inversion of the CD4+/CD8+ ratio was detected in most patients during both intramuscular gammaglobulins (IMIG) and IVIG therapy. PMID- 1306341 TI - Use of single voided urine samples to estimate quantitative proteinuria in children. AB - Quantitation of protein excretion in urine is used for diagnostic and prognostic purposes and also to assess the effects of therapy in children. The method in common use is to measure urinary protein in a 24-hour urine sample, which may be time consuming and is often inaccurate. The aim of this study was to determine if the urine protein/creatinine ratio in a single-void urine sample had a high correlation with the quantity of protein in a 24-hour urine specimen. We found that there was an excellent correlation between the protein content of a 24-hour urine excretion and the protein/creatinine ratios in single morning urine samples of 50 patients. We also discovered that a protein/creatinine ratio greater than 4.9 could signify "nephrotic-range" proteinuria, while a ratio less than 2.5 indicated nephritic syndrome or other renal diseases. We concluded that the determination of urinary protein/creatinine concentration ratios in a single morning urine sample under most clinical circumstances, especially in nephrotic syndrome, could replace the measurement of protein excretion in 24-hour urine specimens. PMID- 1306340 TI - Membranoproliferative glomerulonephritis in sibs. AB - Idiopathic membranoproliferative glomerulonephritis (MPGN) is a chronic renal disease with variable clinical expression and several distinct morphological subtypes. Two sibs, aged 10 and 13, presented with clinical and laboratory findings of MPGN at the time of admission. After an interval of one year, the diagnosis of MPGN was established by renal biopsies. The complement pathway was unremarkable. HLA typing in the unrelated parents and the two male sibs revealed common HLA A2,A11,Bw60, DR2,DQw1 antigens in the brothers. Of these antigens, A2 has been reported previously in cases of MPGN. The other antigens regarding this disease need to be evaluated from the standpoint of genetic importance. PMID- 1306342 TI - Analyses of serum vitamin D-binding protein, ceruloplasmin and copper levels in preterm infants. AB - The cord blood specimens of 12 preterm and 20 term babies were investigated. We determined serum calcium (Ca), phosphorus (P), magnesium (Mg), vitamin-D binding protein (DBP), ceruloplasmin (Cp) and copper (Cu) levels in two groups. We found that Ca, P, and MG levels of cord sera did not differ between the groups (p > 0.05), but DBP, Cp and Cu values showed a significant decrease in the preterm group (p < 0.05). The Cu and Cp values of the preterm infants correlated with those of the term infants. PMID- 1306343 TI - Craniosynostosis: a review of 143 surgically-treated cases. AB - In this study, 143 cases of craniosynostosis are presented. There were 109 males and 34 females. The major complaints were skull deformity (92 patients), proptosis (38 patients) and microcephalus (32 patients). Neurological examination revealed the presence of optic atrophy in 24 patients and papilledema in 20 patients. Seventy-four patients (53%) had three or more suture closures, with the sagittal suture being the most commonly involved (20% of patients). All patients underwent surgery. Suture removal was performed in 131 patients (91.7%), suture removal plus orbital decompression in 34 (23.8%), and linear craniectomy plus wrapping in 12 (8.3%). The reoperation rate was 6.2 percent. During the follow-up period, preoperative papilledema and proptosis improved in 88.2 and 78.9 percent of patients, respectively. Skull deformity disappeared in 46.9 percent of patients, but remained unchanged in 16.6 percent. PMID- 1306344 TI - Effects of anticonvulsant drugs on thyroid hormones in epileptic children. AB - Serum total and free thyroid hormones, reverse T3 (rT3), thyroxin binding globulin (TBG) and thyroid stimulating hormone (TSH) concentrations were measured in 35 epileptic patients receiving anticonvulsants (phenobarbitone, phenytoin). There was a significant reduction found in total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and rT3 in the group treated with, phenytoin. The thyroid hormone levels were within normal limits in the group receiving phenobarbitone. PMID- 1306345 TI - Two-dimensional and Doppler echocardiography in the diagnosis of absent pulmonary valve syndrome (surgery without catheterization). AB - The majority of severely affected infants with absent pulmonary valve syndrome develop varying degrees of respiratory distress. Cardiac catheterization and angiocardiography are still performed in the diagnosis of these infants prior to surgery. However, considering the high risks of these invasive investigations for severely symptomatic infants, diagnosis using only noninvasive methods becomes important. In this regard, we present three cases of absent pulmonary valve syndrome, diagnosed pre-operatively by both two-dimensional and Doppler echocardiography. The diagnosis was confirmed by cardiac catheterization and angiocardiography in two cases and by surgery in a symptomatic infant. Therefore, we are of the opinion that the two-dimensional and Doppler echocardiographic methods are most reliable in diagnosing absent pulmonary valve syndrome, and that severely symptomatic infants can be referred for surgery without catheterization. PMID- 1306346 TI - A case of juvenile chronic myeloid leukemia with XX/XXX mosaicism. AB - Cytogenetic abnormalities are rarely found in patients with juvenile chronic myelogenous leukemia (JCML). In patients with chromosomal abnormalities, chromosomes 7 and 8 are usually involved. A case of JCML with 47 XXX and a 46 XX karyotype is described and the literature is reviewed. To our knowledge, this is the first case ever to have been reported. PMID- 1306347 TI - Intussusception due to ectopic pancreatic tissue in a nine-month-old child. AB - Ileo-colic intussusception was diagnosed in a nine-month-old male infant who presented with abdominal distention, irritability, and bilious vomiting. After reduction of the invaginated segment, a mass measuring one cm was palpated at the antimesenteric border of the terminal ileum. Pathological examination of the mass revealed ectopic pancreatic tissue, which most likely caused the intussusception. PMID- 1306348 TI - Primary lymphedema precox of the penis and its surgical treatment: a case report. AB - Primary penile lymphedema occurs infrequently and is seen in conjunction with a similar process in the scrotum. The accepted form of treatment is surgery since conservative medical treatment is of little value. Different surgical techniques have been described, but no single procedure has emerged as the ideal treatment. Radical excision of all lymphedematous tissues and reconstruction using local penile flaps yield excellent functional and cosmetic results. We treated a 13 year-old boy with primary penile lymphedema precox using radical excision and reconstruction with local penile flaps. At follow-up two years later, functional and cosmetic results were satisfactory. PMID- 1306349 TI - Wolman disease: suggestions for effective treatment. PMID- 1306350 TI - Therapeutic trial in Wolman disease. PMID- 1306351 TI - Does this patient need a narcotic injection? A descriptive analysis of decision making. AB - Thirty six nurses divided into three groups were asked in a series of three questionnaires to evaluate patients' needs for post-operative narcotic pain relief. Using a decision-analytic procedure, which combined a version of the Delphi technique and the multi-attribute utility approach, the six most salient criteria in order of priority were identified. These criteria were then tested in the clinical situation using a series of scenarios. A difference between how nurses purportedly evaluated patients' needs for narcotic pain relief and what they actually did in hypothetical clinical situations was found. The theoretical implications of these results are discussed. PMID- 1306352 TI - Transforming mediocrity to excellence: a challenge for nurse leaders. AB - A grounded theory study of nursing leadership in Western Australia was undertaken to shed light on complex contextual and individual variables associated with nursing leadership. By applying the constant comparative method of data analysis, the core problem facing nurse leaders was identified as overcoming and compensating for disadvantage related to a repressing context which impeded the movement of nursing from retardation and mediocrity, through turbulence and toward excellence. Following a long period of stagnation (reflecting mediocrity in the nursing system) and a shorter evolutionary phase, revolutionary changes were being implemented, creating an extremely turbulent environment. Findings revealed that nurse leaders used a core process labelled optimising to deal with the core problem and to achieve influence and advancement. This process had progressive phases identified as surviving, investing, and transforming. Failure to optimise led to floundering. Transforming reflected exceptional performance or excellence and involved using the optimising strategies of reversing negative situations and creating additional resources to achieve influence and significant advancement or change in the nursing system. This study has implications for leadership practice, for the development of future leaders and for future research and theory development. PMID- 1306353 TI - Passing school biology: a predictor of success in nursing science courses? AB - A correlation was found between students' SA Year 12 public examination school biology scores and subsequent success in an undergraduate nursing science course. The group of students most successful in science courses had a higher mean school biology score than the group who were least successful. Some mature age students with no background in science were able to perform as well as those who had passed publicly-examined biology at school. Hence biology should not be a prerequisite for mature age entrants. PMID- 1306354 TI - Accidental falls and injuries among seniors. AB - This study analyzes data on accidental falls for those aged 65 and older. The data are based on mortality statistics from 1980 to 1989 and morbidity statistics from 1985 to 1989. These statistics are provided to the Canadian Centre for Health Information by the provincial governments. Mortality rates and hospital separation rates for accidental falls are highest for those aged 65 and older. Accidents are one of the leading causes of death and hospitalization among seniors. In 1989, for those aged 65 and older, accidental falls accounted for 56% of accidental deaths and 65% of accident-related hospital separations. Mortality and hospital separation rates for accidental falls increased with age. For those aged 65 and older, the mortality rates for accidental falls were higher for men than women. However, the accident-related hospital separation rate was higher for women than men. The reason for this difference is not fully understood, but it has been suggested that while more women fall than men, more men seriously injure themselves. For men requiring hospitalization due to accidental falls, the most common injuries, in descending order, were fractures of the hip, ribs, vertebral column, humerus, and pelvis. For women, the most common injuries were fractures of the hip, humerus, radius and ulna, pelvis, and ankle. Of fall-related injuries resulting in hospitalization, hip fractures were the leading cause of death and proportionately more men than women died of hip fractures. PMID- 1306355 TI - Measures of outside care given and received by seniors. AB - Selected data from Cycle 5 of the 1990 General Social Survey are presented in this study. Among other topics, this article focuses on the provision of caregiving services to the population aged 65 and over by persons outside the recipients' household. Although assistance is often received from family members, it is also provided by friends, neighbours, and other members of the community. Persons whose health was good or excellent were more likely to be caregivers than those who rated their health status as poor. However, several persons in the latter category did offer their support despite their poor health. Satisfaction with the aspects of life examined in this study did not vary markedly between caregivers and non-caregivers. PMID- 1306356 TI - Reductions in age-specific mortality among children and seniors in Canada and the United States, 1971-1989. AB - We compared mortality rates for children and seniors in Canada and the United States in 1971 and 1989. Children in Canada experienced a greater decrease in mortality during this period than did all children in the United States. In particular, while mortality rates for both boys and girls in Canada were higher than those for White children in the United States in 1971, in 1989 the rates for Canadian children were lower. Seniors in Canada experienced a similar or lesser reduction in age-specific mortality than did seniors in the United States. Even though senior women in the United States experienced a reduction in mortality comparable to that of senior women in Canada, Canadian senior women in general had lower level of mortality than their counterparts in the United States. Senior men in the United States experienced a relatively greater reduction than did their counterparts in Canada. The greater decline in mortality for senior men in the United States enabled them to catch up with the lower level of mortality for their Canadian counterparts in 1989. These general conclusions apply whether we compare the Canadian experience to that of the entire population or the White population in the United States. These trends in mortality reductions may reflect the fact that free universal Medicare is available for all ages in Canada, while most publicly-funded Medicare entitlements begin at age 65 in the United States. PMID- 1306357 TI - An investigation of the increase in preschool-age asthma in Manitoba, Canada. AB - Asthma has long been a major cause of illness and disability among young Canadians. From 1970-71 to 1987-88, hospital admissions for asthma increased significantly among Canadian children under the age of fourteen. Many hypotheses may explain this increase in asthma prevalence. There could be a true increase in the number of people developing symptoms of the disease or increased asthma rates could be an artifact due to changes in detection, diagnosis, treatment, or coding. This study reviews hypotheses put forward to explain the increase in asthma prevalence, and tests some of them in Manitoba for children aged 0-4. Physician claims data and hospital separation data were merged to create unique person oriented medical records. These records were used to estimate the number of children seeking medical services for asthma during a five-year period (1984 85 to 1988-89) and the change in rates over this time period. From 1984-85 to 1988-89, both prevalence and incidence rates for children less than five years of age increased. Prevalence rates showed strong seasonal peaks in the spring and the fall. There is no indication that asthma increased in severity. The hospitalization rate (the number visiting a hospital for asthma divided by the total number seeking medical care for asthma), the average number of hospital admissions per year, and the average number of days spent in a hospital per year did not increase. Levels of ozone (O3) and nitrogen dioxide (NO2) in downtown Winnipeg increased over the study period and asthma prevalence increased twice as fast in Winnipeg as in the rest of the province. For Manitoba, the increase in preschool-aged asthma does not appear to be due to increased use of medical services, a change in ICD coding, an increase in the severity of the cases, or a decrease in income levels. The increases appear to be at least partly due to changes in diagnostic practices. The relationship between asthma and air pollution needs more detailed study as pollution is likely to be an important factor, particularly during the spring. Other areas for further investigation are changes in allergy and virus precursors, maternal smoking, and increased levels of pollens, molds and dust mites. PMID- 1306358 TI - Demographic trends of marriages in Canada: 1921-1990. AB - This paper mainly describes levels and trends of marriages and rates and its relationship with demographic and social conditions in Canada from 1921 to 1990. In Canada, the propensity to marry was much higher in the 1960s and early 1970s than in the 1980s. A similar tendency was observed for a few years prior to, and at the beginning of, World War II and a couple of years after. The number of marriages peaked at an all time high of 200,470 in 1972 with a rate of 44.3 per 1,000 unmarried population aged 15-59. By 1986 the number of marriages had declined by 12.4% and the rate by 33.2%, but both the number of marriages and the rate increased marginally in the following three years. Since 1921 the average age at marriage has increased by 3.6 years for brides and 1.7 years for grooms. The proportion of marriages by previously divorced persons increased sharply after 1968. The changes in marriage rates in Canada parallel those exhibited in the United States and other developed countries in the western hemisphere. PMID- 1306359 TI - Is the "war against cancer" lost? PMID- 1306360 TI - Management of patients with ovarian cancer using monoclonal antibodies. AB - We describe in detail the current trend using monoclonal antibodies to diagnose ovarian cancer either in vitro or in vivo. The approach with such powerful reagents allows to differentiate in vitro tumor histotypes and to detect in peritoneal washings the presence of a few neoplastic cells which characterize the minimal disease. The detection of elevated sera levels of ovarian cancer associated antigens, such as CA-125 and TAG-72, allows the monitoring, follow-up of these patients and the response to therapy with great accuracy. We focused our attention on the role in vivo of labelled monoclonal antibodies, mainly for diagnostic purposes. Radioimmunoscintigraphy has been found to be more reliable than CT and US to detect foci of disease mainly in patients already treated by surgery, overcoming all the problems usually encountered with these two procedures. PMID- 1306361 TI - Current status of interleukin-2 therapy in cancer. AB - In vitro studies and animal experiments showed the existence of a physiological immune response against tumors. Interleukin-2 was the first immunological agent which demonstrated an anti-tumor effect by activating immune effectors. In vitro IL2 may generate Lymphokine Activated Killer (LAK) cells from peripheral blood lymphocytes or Tumor Infiltrating Lymphocytes (TIL) expanded from tumor. In melanoma and renal cell carcinoma, IL2 alone or associated with LAK cells or TIL, mediated clinical responses. However, their clinical efficacy was associated with some toxicity related to a capillary leak syndrome. This implies an improvement in the selection of patients and in the understanding of IL2 action. Future directions in immunotherapy included combination IL2 with other cytokines or monoclonal antibodies or chemotherapy. Lymphokine gene therapy is designed to introduce IL2 or other cytokine genes into tumor infiltrating lymphocytes or directly into tumors to reduce systemic toxicity and to achieve high local cytokine concentration. Animal models and the first human trials make this approach promising. PMID- 1306362 TI - Variation of choline-substituted lipid metabolism in doxorubicin-resistant leukemia cells. AB - In adriamycin-resistant murine (FLC) and human (K562) leukemia cells, phosphatidylcholine increases and phosphatidylethanolamine decreases compared to adriamycin-sensitive lines. This change is due to an increase in phosphatidylethanolamine methylation. The choline pathway of phosphatidylcholine biosynthesis is also disturbed in resistant cells with a blocking step of CDP phosphocholine transferase and a decrease in sphingomyelinase activity. These changes in phospholipid metabolism are suggested to be responsible for the changes in membrane fluidity reported previously (Tapiero et al, 1986) for resistant cells. PMID- 1306363 TI - Anti-infectious effect of C granulosum-derived P40 immunomodulator given by aerosolization and intranasal instillation. AB - It is known that C granulosum-derived P40 immunomodulator displays strong anti microbial effects in mice by the intravenous route. Since microbial contamination of humans occurs in many instances via the airways, the effect of P40 on infections was investigated when it was given intranasally or by aerosolization. In order to augment its bioavailability, P40 was derivatized by coupling with polylysine chains (P40-PL). The results showed that P40-PL exercised a significant protective effect, both by the intranasal route and by aerosolization on both influenza and K pneumoniae infections produced by aerosolization or intranasal instillation. Stimulation of the phagocytic capacity of alveolar macrophages by these types of treatment is likely to account for the increased resistance of mice toward microbial infections. PMID- 1306364 TI - Nitric oxide mediates the depression of lymphoproliferative responses following burn injury in rats. AB - Among the multiple biological activities of nitric oxide (NO) an immunoregulatory role consisting of the mediation of macrophage suppressive activity, has recently been evidenced. In the present work, we investigated whether NO was implicated in immunosuppression following burn injury. Thermal injury affecting 20-25% of the total body surface area in Wistar rats, provoked a biphasic depression of spleen cell proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A). We show that these responses are fully restored on day 4 after burn and only by 55% on day 10 when spleen cells were stimulated in the presence of NG monomethyl-L-arginine (NMMA), a potent inhibitor of the macrophage inducible NO synthase. Nitrite content in culture supernatant, as an indicator of NO release (in the absence of NMMA), was significantly augmented in Con A-stimulated spleen cells from burned rats as compared to normal spleen cells. These results show for the first time that NO is implicated, at least in part, in an immunosuppression state which is not linked to an infectious disease. PMID- 1306365 TI - The dynamics of a hydrogel strip. AB - A hydrogel strip relaxes when it is stretched. The decay in tensile stress can be ascribed primarily to strain-induced swelling of the polymer network--a result that follows from a continuum model of the gel-solvent system. An equation of motion and a linear constitutive law of the polymer network, Darcy's law, and the conservation of mass of the network and interstitial fluid are solved with boundary and initial conditions appropriate for a stress-relaxation experiment. This model predicts that the time constant of decay depends inversely upon the square of the thickness of the sample. This result is confirmed by experiments. In addition, the network shear modulus, mu, bulk modulus, k, and hydraulic permeability, 1/f, which are estimated by non-linear regression, all agree with measurements obtained using other methods. PMID- 1306366 TI - Mathematical model of the filtration in the vascular network of the ophidian glomerulus. AB - The present work is a mathematical model of the fluid filtration in the glomerular network occurring in snakes. The model is based on the differential form of Starling's hypothesis and takes into account the angioarchitecture of the network and the behaviour on the microrheology of blood with nucleated red cells. The model predicts the hemodynamics and the transvascular fluxes in each vascular segment within the network. The model is applied to a vascular network of the glomerulus of the garter snake. A value of 0.593 microns/(s.mmHg) was determined for the hydraulic conductivity of the glomerular capillaries using the geometrical data of the network together with experimental data for the pressures and the blood flow rate reported in the literature. The analysis shows that the local filtration rates cover a wide range. In some of the vascular segments, the filtration leads to such a high increase in colloid-osmotic pressure that the level of the transvascular hydrostatic pressure difference is reached. Mathematical simulations of the variation of the glomerular blood flow rate due to vasoactivity of preglomerular arterioles show the effect on the filtration rate and the hemorheologic parameters. PMID- 1306367 TI - influence of concentration and mannuronate/guluronate [correction of gluronate] ratio on steady flow properties of alginate aqueous systems. AB - Steady flow properties were measured at various concentrations for aqueous systems of alignates with different mannuronate/gluronate (M/G) ratios using a cone-plate type rheometer. The flow curve (a plot of shear stress vs. shear rate) shows a plateau region, which is ascribed to a heterogeneous structure, at low shear rate. This plateau region is more noticeable in the G-rich systems than in the M-rich systems. On the other hand, the flow curves for the systems with the same molecular weight but different M/G ratios are congruent in the high shear rate region. The zero shear viscosity can be reduced by the segment contact parameter, cMw, for the alginates with the same M/G ratio but different molecular weights. The zero shear viscosity is proportional to cMw in a low concentration region and is proportional to (cMw)3.4 at relatively high concentrations. The critical value of cMw for which the zero shear viscosity changes from proportionality with cMw to proportionality with (cMw)3.4 is ca. 900. PMID- 1306368 TI - Experimental analysis of the influence of stenotic geometry on steady flow. AB - We studied the flow behavior under steady flow conditions in four models of cylindrical stenoses at Reynolds numbers from 150 to 920. The flow upstream of the constrictions was always fully developed. The constriction ratios of the rigid tubes (D) to the stenoses (d) were d/D = 0.273; 0.505; 0.548; 0.786. The pressure drop at various locations in the stenotic models was measured with water manometers. The flow was visualized with a photoelasticity apparatus using an aqueous birefringent solution. We also studied the flow behavior at pulsatile flow in a dog aorta with a constriction of 71%. The flow through stenotic geometries depends on the Reynolds number of the flow generated in the tube and the constriction ratio d/D. At low d/D ratios, (with the increased constriction), the flow separation zones (recirculation zones, so-called reattachment length) and flow disturbances increased with larger Reynolds numbers. At lower values, eddies were generated. At high Re, eddies were observed in the pre-stenotic regions. The pressure drop is a function of the length and internal diameter of the stenosis, respective ratio of stenosis to the main vessel and the Reynolds numbers. At low Re-numbers and low d/D, distinct recirculation zones were found close to the stenosis. The flow is laminar in the distal areas. Further experiments under steady and unsteady flow conditions in a dog aorta model with a constriction of 71% showed similar effects. High velocity fluctuations downstream of the stenosis were found in the dog aorta. A videotape demonstrates these results. PMID- 1306369 TI - Correlation between rheologic properties and in vitro ciliary transport of rat nasal mucus. AB - The relationship between mucus rheologic variables and in vitro ciliary transport was investigated in mucus samples collected from the upper airways of 30 Wistar rats. In vitro mucus transportability was determined by means of the frog palate preparation. Rheologic evaluation was done by measuring the rigidity modulus (log G*, representing the vectorial sum of viscosity and elasticity) and the loss tangent (tan delta, i.e. the ratio between viscosity and elasticity) at 1 and 100 radian/s using a magnetic microrheometer. The correlation between the rheologic variables and in vitro mucus transportability was made by stepwise multiple linear regression analysis, with frog palate transport rate considered as the dependent variable. A significant relationship was obtained between the rheologic parameters (log G* and tan delta) measured at 1 radian/s and the frog palate transport ratio. The relative speed of mucus samples was related to rheology according to the following relationship: rat/frog speed ratio = 1.666-0.434 log G*-0.331 tan delta, for G* and delta determined at 1 radian/s (multiple r = 0.666, p < 0.001). Transport rates predicted from the above formula gave a satisfactory fit to those observed in a second set of 30 rats. The present results indicate that the overall mucus impedance, as well as the ratio between viscosity and elasticity, are important in determining the efficiency of clearance. In addition, it was shown that measurements performed by applying relatively low frequency deformations are preferable for predicting ciliary transport. PMID- 1306370 TI - Alfred L. Copley, the teacher and founder. PMID- 1306371 TI - A.L. Copley, the medical scientist and biorheologist. PMID- 1306373 TI - Tribute to A. L. Copley. PMID- 1306372 TI - Changes in the rheological properties of blood vessel tissue remodeling in the course of development of diabetes. AB - Rheological properties of blood vessels are expected to change in disease process if the structure of the vessel wall changes. This is illustrated in diabetes, which can be induced in rat by a single injection of Streptozocin. One of the rheological properties of the blood vessel is the stress-strain relationship. The nonlinear stress-strain relationship of arteries is best expressed as derivations of a strain-energy function. In this paper, the stress-strain relations are measured and the coefficients in the strain energy function of arteries are determined for diabetic and control rats. The meaning of these coefficients are explained. The influence of diabetes on the elastic property of the arteries is expressed by the changes of these coefficients. A point of departure of the present paper from all other blood vessel papers published so far is that all strains used here are referred to the zero-stress state of the arteries, whereas all other papers refer strains to the no-load state. The existence of a large difference between the zero-stress state and no-load state of arteries is one of our recent findings. We have explained that the use of zero-stress state as a basis of strain measurements reveals that the in vivo circumferential stress distribution is quite uniform in the vessel wall at the homeostatic condition. It also makes the strain energy function much more accurate than those in which the residual stress is ignored. Using these new results, the stress and strain distribution in normal and diabetic arteries are presented. PMID- 1306375 TI - Red cell membrane elasticity as determined by flow channel technique. AB - The elasticity of red cell membrane was determined in a rectangular flow channel under controlled shear flow. The relation between shear stress and cell extension ratio (lambda) has been analyzed with the use of Evans' two-dimensional model. The deformed cell shapes observed experimentally agreed well with the model with lambda up to 1.4. The best correlation was found at lambda = 1.2. The analysis suggests a nonlinear extensional membrane modulus in the low stress range encountered in the flow channel. In terms of an appropriate strain parameter, the elastic modulus is shown to rise toward the level encountered in micropipette aspiration experiments. The implications of the present findings in modeling of cell mechanics and in cell hemolysis are discussed. PMID- 1306374 TI - Dynamics of cell movement during the wound repair of human surface respiratory epithelium. AB - Epithelial wound repair represents an important process by which the epithelial barrier integrity recovers after wounding. To evaluate and quantify the dynamics of surface airway cell movement during the wound repair process, we developed an in vitro wounding model of human respiratory cells in culture and we analyzed the wound repair by using videomicroscopic and image analysis techniques. We observed that wound closure occurred within 6 hours, due to the spreading and migration of the cells surrounding the wounded surface. The migration rate of the cells at the leading edge of the wound surface increased progressively up to 26 microns/h during the repair process which was characterized by a uniform centripetal direction of cell movement. The distance travelled by these cells was 2.5 fold longer than the distance travelled by ciliated cells which were located far from the wound area. These results suggest that cell migration after wounding is an important process by which the respiratory epithelial barrier integrity is maintained. PMID- 1306376 TI - An interpretation of partial plug flow of concentrated suspensions. AB - The partial plug flow of a concentrated suspension of rigid particles in a circular tube has been previously studied experimentally. It has been shown that a central core may exist in which the mean velocities of the particles and the suspending fluid are equal and constant within a cylindrical core of the flow. This behavior has been attributed to hydrodynamic interaction of the particles within the core. In the present analysis this interaction is interpreted in terms of passing vs. non-passing motions of adjacent particles. A hypothesis of a critical parameter alpha c involving the shear stress and the pressure gradient is explored and a new form of the relation of core diameter to particle size and concentration is developed based on alpha c. PMID- 1306377 TI - Platelet thrombi produced on cultured endothelial cells by the dye/light method. AB - Platelet adhesion and aggregation were induced on cultured endothelial cells using the fluorescent dye/light method. A cone-and-plate apparatus was newly developed to observe interactions between platelets and cultured endothelial cells under a shear flow condition. The platelet deposition grew on the light irradiated area of the cells. Degree of endothelial cell injury induced by the dye/light reaction seemed to depend on the dye concentration. Application of either aspirin or indomethacin significantly inhibited the growth of platelet aggregation, but was not effective for the platelet adhesion to endothelial cells. The platelet thrombi were formed on endothelial cells without their denudation. It was found by transmission electron microscopy that platelets directly adhered to endothelial cells which were not seriously damaged. This thrombus model is expected to be applicable to some physiological and pharmacological studies investigating platelet-endothelial cell interaction and mechanism of platelet thrombus formation in blood vessels. PMID- 1306378 TI - Fabrication of glass micropipettes: a semi-automatic approach for trimming the pipette tip. AB - Micropipettes as research instruments are well established in cell biology, including blood rheology. However, the experimental results are, to some extent, dependent on the quality of the pipette itself; it is usually critical to have the desired pipette internal diameter and a perpendicular tip. Pipette fabrication is a two-step procedure involving: a) the pulling of the pipette from a glass capillary; b) the trimming of the pipette tip. A common method to trim and fracture the pipette tip is the use of a melted glass bead on a heated tungsten wire. Previous devices using this method were often associated with problems because the heated wire varied in length with temperature. As a result, the bead together with the attached pipette tip moved markedly and thus hampered the possibility to obtain a perpendicularly cut pipette tip. An improved design, based on the same principle with a melted glass bead, is thus suggested; it eliminates the problem with a moving glass bead and, in addition, allows semi automatic pipette trimming by utilizing the heat-induced elongation/retraction of the heated wire to fracture the tip without requiring manual assistance. Furthermore, a simple pipette storing technique is suggested, based on standard laboratory utensils, in order to more easily handle fragile pipettes without risk of breakage. PMID- 1306379 TI - Membrane labelling by fluorescent probes: incorporation of TMA-DPH in erythrocyte membranes. AB - A study of the labelling of isolated resealed erythrocyte membranes by TMA-DPH has been carried out. A quantitative study shows that saturation appears to take place when increasing the relative quantity of probe bulk concentration to membrane concentration; this is readily interpreted by a simple incorporation model with a limited number of sites in the membrane. A qualitative study shows that an increase in the labelling leads to an evolution of the probe fluorescence properties; the existence of different types of sites is involved in the interpretation but the system is too complex to allow it to be represented by a simple model. As a consequence of this study, care has to be taken in labelling biological material so as to avoid excessive probe incorporation. PMID- 1306380 TI - Rheology of the vitreous body. Part I: Viscoelasticity of human vitreous. AB - The rheological properties of the vitreous body of the eye are believed to be a function of composition and to differ among species, as well as to vary regionally within the vitreous. These properties are essential to the mechanical functioning of the eye. Although there are gross, qualitative data on vitreous rheology available in the literature, quantitative rheological measurements on human vitreous and on eyes of other species are sparse and incomplete. The aim of the research reported in this series of papers is to study the rheological behavior of human, bovine, and porcine vitreous, to measure the macromolecular and electrolyte content of these samples, and to correlate and compare these values for the different species as a function of location in the vitreous. In this paper, the rheological model used to correlate viscoelasticity of the vitreous is presented, and a detailed description of the rheological instrumentation and methods of analysis used is given. Data on the rheological properties of human vitreous, as a function of location within the eye, are presented. The results show that in the human eye there are significant differences in a number of the viscoelastic parameters as a function of location within the vitreous body. PMID- 1306381 TI - A model of the factors affecting interstitial volume in oedema. Part I: Hierarchies, some new factors and their equations. AB - A mathematical model has been constructed to investigate the alterations, in amount and in importance, of the Factors controlling interstitial fluid volume in a number of steady-state oedemas. There are many so-called "Safety Factors" (at least 15), including a whole group concerned with regulating the amount of protein in the tissues (and thus tissue colloidal osmotic pressure). They are often in long hierarchies (of even up to 11 Factors), each influencing the next. Sometimes a Factor is recursive, i.e., it influences itself (either positively or negatively) via a Hierarchy of other Factors. The effects of some Factors differ in different Hierarchies, i.e., an increase in the Factor will increase VI via some of the Hierarchies and decrease it via some other Hierarchies. Which effect is most important varies with the Hierarchies and conditions existing at the time. The Factors are best compared if expressed in the same units: ml/min/100g of tissue. This is possible via appropriate multiplication factors derived from the relevant equations. PMID- 1306382 TI - Spontaneous activation of circulating granulocytes in patients with acute myocardial and cerebral diseases. AB - Recent animal studies have suggested that there exists an activated subpopulation of circulating granulocytes which plays an important part in microvascular sequestration and tissue injury during shock and ischemia. In this respect, spontaneous granulocyte activation in form of pseudopod formation, a manifestation of actin polymerization, is a high risk for microvascular entrapment. The present investigation was carried out to determine if there is a significant difference in pseudopod formation in vitro between granulocytes obtained from healthy volunteers without symptoms and patients with acute cardiovascular illnesses. Blood samples from 25 healthy volunteers, 12 patients with acute myocardial infarction (AMI) and 12 patients with acute cerebral infarction (ACI) to determine spontaneous pseudopod formation in granulocytes with a high resolution light microscope over a period of several hours. The results revealed that the mean percentage of cells with pseudopod formation in the control group was below 10% in the first 3 hours, and increased to about 50% at 12 hours. In AMI patients, the level of activation within the first hour was not significantly different from the controls, but it rose rapidly to 90% in 4 to 5 hours. Patients with cerebral infarction, however, showed no significant difference from the control group. When the granulocytes of healthy subjects were incubated in plasma of AMI, the cells were activated similar to AMI granulocytes in their own plasma. When AMI plasma was serially diluted with Ringer's solution, the activation curve fell successively. These results indicate that AMI patients' blood contains plasma factor(s) which can activate granulocytes at a more rapid rate than controls. PMID- 1306384 TI - Fibrin layer inhibits protein leakage from capillaries having dysfunctioning anionic barrier. PMID- 1306383 TI - Some flow visualization and laser-Doppler-velocity measurements in a true-to scale elastic model of a human aortic arch--a new model technique. AB - Flow studies were done in an elastic true-to-scale silicone rubber model of an aortic arch to study further hemodynamic influences on atherosclerosis. The model was prepared from a cast of a young woman. A revised model technique was used. The model had a compliance similar to that of the human aortic arch. Velocity measurements were done in the model with a two component laser-Doppler-anemometer in steady and pulsatile flow using a calcium chloride solution with a viscosity of eta = 3.18 mPas and density of rho = 1.28 kg/m3 at 20 degrees C. The time average Reynolds numbers over a whole cycle in the ascending aorta was Re = 1350. The Womersley parameter for pulsatile flow was a = 20. The pulse wave velocity in the ascending aorta was about c = 5.4 m/sec. The secondary flow behavior was discussed for steady and pulsatile flow. Reverse flows were found, especially along the inner radius of the aortic arch in the descending aorta in steady and pulsatile flow and also in small areas of the ascending aorta and at the branches of the aortic arch. The formation of atherosclerotic plaques at preferred local flow regions is discussed. PMID- 1306385 TI - Dysarthria associated with focal unilateral upper motor neuron lesion. AB - Speech motor changes in six patients with focal unilateral upper motor neuron (UUMN) lesions were characterised using a variety of techniques including listener judgements, speech acoustic analyses, electromyographic and strength measures. Listener judgements of speech understand-ability, intelligibility and dysarthric features indicated mild dysarthria. Diadochokinesis, electromyographic and strength measures corroborated these observations. The findings of this study delineate the characteristics of the dysarthria associated with unilateral upper motor neuron lesions and have important implications for identifying potential upper motor neuron components of other neurogenic disorders of speech and language. PMID- 1306386 TI - Confrontation naming in the elderly: the Build-up Picture Test as an aid to differentiating normals from subjects with dementia. AB - This paper reports the results of a study in which the Build-up Picture Test (BUPT) was given to three groups of elderly subjects with 15 subjects in each group: independent, dependent and those with probable senile dementia of the Alzheimer type (SDAT). The BUPT is a task designed to combine confrontation and generative naming, incorporating priming, cueing and latency aspects to facilitate responses. It involves presentation of degraded line drawings of objects, built up in stages to black and white photographs of the objects. Results showed the scores by the probable SDAT subjects to be highly significant at the 1.00 level (P = 0.0000). Analysis of scores showed better than expected responses from the probable SDAT subjects to representations of familiar objects with simple outline shapes. The implications for differential diagnosis are discussed. PMID- 1306387 TI - Factors influencing accuracy of estimation of comprehension problems in patients following cerebrovascular accident, by doctors, nurses and relatives. AB - Previous work has shown that doctors, nurses and relatives are inaccurate at estimating the comprehension problem of stroke patients. Possible factors that influence the accuracy of these judgements were studied, including confidence of the respondents, the severity of the comprehension problems of the patients and factors specific to relatives (educational background and the length of the relative's relationship with the patient). Doctors, nurses and relatives involved with 30 recently aphasic stroke patients were asked to estimate how patients would perform on the comprehension sections of two tests (Western Aphasia Battery and Functional Communication Profile). Results show that although all respondents over-estimated patients' comprehension abilities, they were more accurate for patients who had mild problems. Doctors and nurses who were more confident about their predictions tended to be more accurate on some parts of the tests than those with less confidence, whereas relatives were equally inaccurate when giving high and low confidence judgements. Length of relationship and educational level did not predict relative's accuracy. PMID- 1306388 TI - Parental recall of children's early development. AB - This study investigates the accuracy of mothers' memories of their child's developmental milestone when the child has reached the age of 4-5 years. Certain aspects of development were well remembered; others, including some speech milestones, were not recalled accurately. PMID- 1306389 TI - The assessment of symbolic play in young children: a prototype test. AB - In this paper it is argued that assessing symbolic play (defined as one object substituting for another, a property being attributed to an object which it does not have or an absent object being referred to as if present) is particularly useful for young children in whom language and/or play is not developing normally. A new test of symbolic play is described which assesses the child's ability to substitute her- or himself, a teddy or a non-representational object such as a piece of material for another object, to attribute a property to her- or himself or a teddy, and to refer to an absent object used by her- or himself or a teddy. The play may be modelled or instructed or the child may produce examples of her or his own. Some preliminary results from a group of 43 children are reported. It is concluded that this new test of symbolic play will provide clinicians working with children whose language and/or play is impaired with information of value in reaching a diagnosis and in understanding immediate treatment needs. PMID- 1306390 TI - Language screening in preschool Chinese children. AB - The incidence of language delay in Chinese preschool children was studied by a stratified proportional sampling of all 3 year olds in Hong Kong. The Developmental Language Screening Scale (DLSS) devised for use with Cantonese speaking children was used to identify children with language delay. Of 855 children sampled in the stage I screening procedure, 4%, 2.8% and 3.3% were identified as having delay in verbal comprehension, expression or both respectively. The stage II clinical diagnostic study included a randomly selected group of children screened in stage I with or without any associated behavioural problem. Among these, 3.4% were identified as having a language delay using the Reynell Language Developmental Scale (RDLS) with a criterion of language age of less than or equal to two-thirds of the chronological age; 3% had specific language delay using the criteria of language age less than or equal to two thirds the chronological age and developmental age more than or equal to two thirds the chronological age. More boys were found to have language delay, although this was not statistically significant. PMID- 1306391 TI - "A day on Ward E" Johns Hopkins Hospital 1928-29. PMID- 1306392 TI - Maternity nursing in Ghana. PMID- 1306393 TI - El Salvador's health needs. PMID- 1306394 TI - Helena Barnard: first president of Johns Hopkins Nurses' Alumni Association. PMID- 1306395 TI - Caring for people with AIDS: one student's experience. PMID- 1306396 TI - Shiftwork strategies: retaining night nurses. PMID- 1306397 TI - Managing verbal abuse. PMID- 1306398 TI - Nurses not heard in the health promotion movement. PMID- 1306399 TI - Longitudinal panel analysis of nursing registrant data. PMID- 1306400 TI - Psychosocial adjustment in post-menopausal women. PMID- 1306401 TI - A profile of part-time faculty in Canadian university nursing programmes. PMID- 1306403 TI - The nursing performance of preceptored and non-preceptored baccalaureate nursing students. PMID- 1306402 TI - [Sources of stress perceived by caregivers: a phenomenological study]. AB - The purpose of this phenomenological study was to identify the sources of stress experienced by caregivers. Twenty-five spouses were interviewed. All were taking care of their husbands who were living at home with a chronic illness. Two instruments were used: a sociodemographic questionnaire and a semi-structured interview developed by Desjean, Doucet, and Gagnon (1983) specifically for phenomenological studies. Interviews were audiotaped, transcribed, and analyzed by Giorgi's test. The results indicated that being a caregiver is stressful. The unsatisfied needs for education and social support, the uncertainty about the outcome of the illness, and the loss of freedom and social activities are the major sources of stress expressed by caregivers. These findings should encourage nurses to evaluate the caregivers' situation and initiate interventions that assist them in decreasing sources of stress. PMID- 1306404 TI - [Comparative study of Legionella pneumonia and other nosocomial-acquired pneumonia]. AB - We studied 20 cases of legionella pneumonia and 23 cases of non-legionella pneumonia. Hyponatremia, elevated GOT and GPT were higher (P < 0.05) in legionella pneumonia group. In spite of the number of cases with diarrhoea, dyspnea, nervous symptoms, myalgia and complication were higher, especially with diarrhoea in legionella pneumonia group when compared to non-legionella pneumonia group, but the number of cases in both types of pneumonia did not show a statistically significant difference. PMID- 1306405 TI - [A clinical study of 50 cases of Legionnaires disease]. AB - The clinical features and X-ray manifestations of 50 cases of legionnaires disease were analysed. 8 cases might be due to nosocomial infection through breathing in flying particles of the saliva or phlegm. According to the main clinical features, this disease could be divided into common pneumonia type; acute gastroenteritis type; encephalopathy type; shock type; acute renal insufficiency type. The differential diagnosis of legionnaires disease with mycoplasmal pneumonia, pneumococcal pneumonia and infiltrative pulmonary tuberculosis was also discussed. The first choice for treatment is erythromycin or erythromycin with rifampicin. PMID- 1306406 TI - [The characteristics and changes in high altitude ventilatory response during acclimatization at 5000 meters altitude]. AB - To assess the characteristics and changes of high altitude ventilation response during acclimatization at 5000m altitude. The poikilocapnic hypoxic ventilatory responses (PHVR) were tested on nineteen healthy men who sojourned 5000m altitude for 12 weeks. The results were that there was a linear correlation between predicated ventilations which were calculated for 5000m altitude depended on PHVR values before ascent and actual ventilations tested when arrived at altitude. The PHVR was increased at second week after ascent, but at twelth week it was dropped near the level before ascent. The authors thought that peripheral chemoreceptor function might be enhanced within a period after ascent. With the acclimatization becomes perfected, the role of compensatory hyperventilation drops gradually to secondary position. So the activity of the chemoreceptor was restored gradually. The PHVR values in Xining group were lower than that in sea level group before ascent, but opposite change appeared at second week at 5000m altitude. There were no significant difference in PHVR between with and without acute mountain sickness groups. PMID- 1306407 TI - [Mutual influence of aminophyllin and cefotaxime in the treatment of pulmonary heart disease]. AB - The serum Aminophyllin (TP) and Cefotaxime (CTX) concentration of the patients of pulmonary heart disease during alute attack were measured by HLPC at 2 h and 6 h after infusion. (1) TP and CTX alone were used (2) TP and CTX were used simultaneously. The result showed that the concentrations of TP were much higher, but CTX were much lower when use CTX and TP simultaneously, at 2 h and 6 h (P < 0.01, P < 0.05). The concentration of TP of pulmonary heart disease with heart failure was higher than without heart failure at 6 h when alone were used or simultaneous were used (P < 0.01), CTX wasn't correlated with heart failure. The concentrations of TP and CTX did not correlate with PaO2 and PaCO2. It showed that TP and CTX would not be used simultaneously. PMID- 1306408 TI - [The breathing pattern and inspiratory drive in chronic obstructive pulmonary disease]. AB - Quantitative analysis of breathing pattern in 20 cases of COPD patients and 15 normal persons showed a significant correlation between values of VT/TI and P0.1; VT/TI value may be used clinically as an index of inspiratory drive. The elevation of VT/TI values of COPD patients at the end of high CO2-rebreathing denoted the sensitivity of their respiratory center is still preserved. However, the impairment of respiratory muscle endurance in hypercapnic COPD patients under rebreathing stress showed a prolongation of TI/TT. PMID- 1306409 TI - [Comparison between radiograph and hemodynamics in obliterative pulmonary vascular disease]. AB - A radiologic-hemodynamic comparitive study was made in 51 cases of obliterative pulmonary vascular disease. The results showed that the pulmonary arterial pressures were all elevated when their radiologic parameters (RDB, RDB/B, PL/T, C/T, DPA/DHT) had abnormal changes, and they had higher sensitivity (76.5-92.2%), specificity (100%) and accuracy (81.8-93.9%) except for DPA/DHT, and there were certain correlations between radiologic parameters and pulmonary arterial pressures (r = 0.36-0.63, P < 0.05-0.01) except for PL/T. In conclusion the radiologic parameters can be used as qualitative diagnostic parameters for pulmonary hypertension in obliterative pulmonary vascular disease, and some parameters might be helpful for evaluating the level of pulmonary hypertension. PMID- 1306410 TI - [Observation on red cell deformability in patients with cor pulmonale]. AB - The measurement of red cell deformability index (RCDI) was made in 29 patients with cor pulmonale and 31 persons of normal controls, at the same time blood gas values and plasma osmolarity were also measured. The results were as follows: (1) The RCDI of patients with acute respiratory and cardiac failure especially with respiratory encephalopathy was significantly lower than that of patient in stable conditions and normal controls. There was no significant difference in RCDI between patients in stable conditions and controls. (2) The PaO2 and pH (in a range of 7.31-7.39) were positively correlated with RCDI. There was no significant difference in RCDI between patients with normal plasma osmolarity and those with abnormal one. We suggested that this might contribute to the increase in pulmonary arterial pressure; and that the hypoxemia and acidosis might play an important role in decrease of RCDI. PMID- 1306411 TI - [Clinical evaluation of the metabolism and imaging of the lung in the patients with chronic obstructive pulmonary diseases using 131I-HIPDM]. AB - The accumulation of venously injected 131I-HIPDM in the rat lung was observed. In this article we report the results of application of 131I-HIPDM in the patients with COPD. The results showed that the metabolism and development of 131I-HIPDM in the lung reflected on condition of the pulmonary endothelial cells or receptors. The clearance curve of HIPDM displayed that COPD, especially COPD of smokers was slow. The analysis of the lung clearance of 131I-HIPDM forms a new index of lung dysfunction. PMID- 1306412 TI - [Facial or nasal mask pressure support ventilation in managing acute exacerbation of chronic respiratory failure in chronic obstructive pulmonary diseases]. AB - 11 COPD patients (age: 65 +/- 9 Yrs) with acute exacerbation of chronic respiratory failure (PaCO2 11.3 +/- 1.1kPa) were treated with mask pressure support ventilation, another 10 similar patients (age: 68 +/- 12 Yrs) served as control. BiPAP ventilator was used with the following modifications: (1) Non rebreathing valve set-in proximal to mask; (2) 5 LPM oxygen flow delivered into mask to reduce the dead space effect. Mask ventilation was given 2-3 hours every time and 1-2 time daily for 7 days. Synchrony and airway patency were specially monitored. The results suggested that mask ventilation could reduce PaCO2, improve PaO2, relieve dyspnea and decrease the possibility of intubation. PMID- 1306413 TI - [The study of alveolar macrophage nitroblue tetrazolium reduction in patients with lung cancer]. AB - Authors studied experimentally PAM NBT reduction function in patients with lung cancer. Results indicate that PMN and lymphocyte counts in the lung cancer group are significantly lower than that in the control group, and NBT reduction of PAM is significantly decreased. We conclude that host defense and immune function in patients with lung cancer are decreased. PMID- 1306414 TI - [Papillary adenoma of the lung-two cases report]. AB - Two rare cases of papillary adenoma of the lung were reported. Histologically, the tumor cells had noninfiltrating papillary growth, cuboidal to columnar with eosinophilc granular cytoplasm and without nuclear atypia. Ultrastructurally, the tumor cells had cytoplasmic osmiophilic lamellar bodies. This benign papillary adenoma of the lung has morphologic characteristics consistent with aveolar type II pneumocyte differentiation. PMID- 1306415 TI - The effect of body fat distribution on cardiovascular risk factors in the population of the Czech Republic. AB - A study of cardiovascular risk factors including anthropometry was performed as part of the MONICA project in 1988 in the population of six districts of the Czech Republic. In addition to probands' weight and height, the circumferences of waist and hips were measured to calculate the index of body fat distribution given as WHR (wast/hip ratio). In the age group of 25-64 years, WHR was significantly higher in men (0.936) than in women (0.836 - p < 0.001); in either sex, its value rose with increasing age. WHR values were statistically significantly higher in this group than those found in a Finnish population where males aged 25-64 years had a mean WHR value of 0.90 (p < 0.001), and women of the same age group had a mean WHR of 0.78 (p < 0.001). An analysis of the relationship between abdominal obesity and some cardiovascular risk factors revealed significant correlations between WHR and total cholesterol (men: r = 0.112, p < 0.001; women: r = 0.122, p < 0.001), HDL cholesterol (men: r = -0.184, p < 0.001; women = -0.23, p < 0.001); atherogenic index, i.e., total cholesterol/HDL cholesterol (men: r = 0.183, p < 0.001; women: r = 0.345, p < 0.001), systolic blood pressure (men: r = 0.295, p < 0.001; women: r = 0.263, p < 0.001), diastolic blood pressure (men: r = 0.32, p < 0.001; women: r = 0.237, p < 0.001). The closest correlation was demonstrated between WHR and BMI (men: r = 0.525, p < 0.001; women r = 0.345, p < 0.001). The authors believe WHR is an important parameter for cardiovascular risk assessment and should be determined on a routine basis. The frequent prevalence of abdominal obesity, as suggested by the high values of WHR, contributes to the high cardiovascular risk of the population of the Czech Republic. PMID- 1306416 TI - Ischaemic heart disease in men of productive age: comparison of epidemiological and morphological data. AB - Data obtained from a cross-sectional population study of men aged 20-54 years and results of a morphological epidemiological examination of the aorta and coronary arteries of 507 men aged 20-59 years, deceased from various causes in the city of Tallinn, were analysed to find whether there is a relationship between the prevalence of ischaemic heart disease (IHD), its risk factors and morphological features of atherosclerosis. An association has been found between the development of clinical IHD manifestations with age, extent of morphological signs of atherosclerosis in the abdominal aorta and coronary arteries, and occurrence of hypercholesterolaemia. Estonian men showed more marked changes in lipid indicators and greater extent of morphological signs of atherosclerosis than men of other nationalities; this corresponds to the more atherogenic character of the former's diet. However, Estonian men did not differ from other nationalities in the occurrence of IHD and expected death risk--a finding the authors explain by the lower percentage of smokers among Estonians. PMID- 1306417 TI - The magnitude of left ventricular myocardial hypertrophy related to the degree of its dysfunction in patients with dilated cardiomyopathy (DCM). AB - The aim of the study was to analyze the relationship between the magnitude of left ventricular (LV) hypertrophy and selected haemodynamic parameters reflecting LV systolic and diastolic function. The "hypertrophy-function" relationship was evaluated in 22 patients with dilated cardiomyopathy (DCM) and in patients with left ventricular dilatation resulting from volume overload due to valve disease (DVOL). The parametres of systolic and diastolic left ventricular function were obtained from right- and left-heart catheterization and quantitative angiocardiography, DCM patients were divided into subgroups depending on the magnitude of hypertrophy and degree of dilatation: Ia- moderate hypertrophy (100 g/m2 < LVMI < 175 g/m2). Ib- massive hypertrophy (LVMI > 175 g/m2); IIa- mass/volume ratio (M/V) < 1.1, and IIb - M/V > 1.1. It was found that the magnitude of myocardial hypertrophy and the M/V ratio do not affect the degree of systolic and diastolic dysfunction in patients with DCM. Myocardial hypertrophy accompanying dilatation due to DCM and DVOL showed very similar progression of impairment of isovolumetric systole and relaxation. Significant differences in EF, LVMDP and LVEDP may result from a different degree of total LV volume stiffness as a consequence of various mechanisms of hypertrophy in DCM and DVOL. PMID- 1306418 TI - A genetic study in hypertrophic cardiomyopathies (Czech population). AB - In order to verify the type of heredity and to identify other genealogical characteristics in the Czech population, the authors examined 105 families with incidence of hypertrophic cardiomyopathy (HCM). The probands' siblings presented a 24-percent empiric risk of the disease; in male probands the risk for brothers was four times that for sisters, in female probands it was three times higher for sisters than brothers. Sex ratio of affected siblings was 20:4 in male and 3:14 in female probands. Disease risk for children was substantially higher in younger probands (under 30 yrs. of age: 40%, above 51 yrs.: 6.7%). Reproduction fitness was decreased in the whole group more so in women. Gene penetration was estimated using the "safe carriers" method, as 50 p.c. Anticipation and more severe course were recorded in all families with HCM incidence in more than two generations. The HCM heredity does not resemble that of the autosomal dominant type. The heterogeneity, phenocopy and sexual modulation could not be excluded. Genetic counselling and, possibly, DNA diagnostics would be necessary to elucidate the hereditary nature of hypertrophic cardiomyopathy. PMID- 1306419 TI - Endogenous digitalis-like factor in patients with acute myocardial infarction. AB - The authors examined endogenous digitalis-like factor (DLF) concentrations in the serum and urine in 65 patients with acute myocardial infarction. Radioimmunoassay was used for the examination and patients' data were analyzed in detail in relation to sex, risk factors and acute myocardial infarction complications. The concentrations of digitalis-like factor found in the serum of men (0.317 +/- 0.026 micrograms/l) and women (0.256 +/- 0.057 micrograms/l) with acute myocardial infarction were much higher compared with values of healthy men (0.009 +/- 0.004 micrograms/l) and women (0.015 +/- 0.012 micrograms/l). This finding is in agreement with data published by others and suggests a role of DLF in the pathogenesis of myocardial infarction. PMID- 1306420 TI - Activity of ATPase and 5'nucleotidase in endothelium of human atherosclerotic aortas. AB - Twenty necroptic atherosclerotic aortas were studied using a modified en face Hautchen preparation method. Endothelium of 1 x 1 cm pieces of aortas was frozen onto slides with the help of dry ice. Endothelial cells on atherosclerotic lesions were irregularly oriented, had ununiform shape and giant multinucleated endothelial cells were present. The endothelial pavement on atheromatous lesions was usually defective. There was increased activity of ATPase and 5'Nase in endothelial cells on atherosclerotic lesions and on their borders. It is suggested that the high activity of ectonucleotidases of the endothelium on atherosclerotic lesions results in rapid dephosphorylation of ATP and ADP released by platelets aggregating to adenosine. Adenosine accumulated in the unstirred layer of plasma in the macrovasculature can effectively inhibit platelet aggregation and subsequent thrombosis on pathologically changed vascular pavement in atherosclerosis. PMID- 1306421 TI - Plasma lipids, lipoproteins and atherogenic index in men and women administered vitamin C. AB - The aim of the study was to establish whether it is possible, in a group of deliberately selected subjects with hyperlipidaemia, to modulate cholesterol levels by ascorbic acid administered at a dose of 500 mg/day. The authors assessed the levels of vitamin C, total and HDL cholesterol, triacylglycerols in the blood serum of 140 probands assigned to an 83-member experimental group, and to a 57-member control group. The experimental group was provided Celaskon effervescens Spofa at a dose of 500 mg/day/person. The experiment lasted for 18 months. Blood collections were made in the whole cohort at six-month intervals. Administration of L-ascorbic acid led to a highly significant decrease in the levels of total and LDL cholesterol. After 12 months of study, a highly significant decrease in atherogenic index and an increase in HDL cholesterol levels were found persisting until the end of the experiment. PMID- 1306423 TI - [Results of anterior transposition of the ulnar nerve at the elbow. Apropos of Le Viet D's communication. December 18, 1991]. PMID- 1306422 TI - Venous wall ultrastructure in generalized venomegaly. AB - The ultrastructure of the v. colica sinistra in a case of generalized vasomegaly in man was examined. Elastic material was found in three forms: as a lightly osmiophil amorphous material bordering on myocytes, as a highly osmiophil elastic membrane, and as highly osmiophil slim elastic fibres of different orientation in the tunica media and adventitia. The slightly osmiophil elastic material is assumed to be newly formed by pinocytotic activity of the myocytes. The highly osmiophil elastic material indicates its impairment. No typical atherosclerotic changes were found in the examined vein. Based on a comparison with previous findings in the case of vasomegaly of the a. mesenterica inferior, the authors conclude that the venomegaly phenomenon is connected with degenerative changes in the elastic material of the vessel wall. PMID- 1306424 TI - [Current role of reconstructive surgery in the treatment of acute mediastinitis after cardiac surgery]. AB - Infected median sternotomy often requires wide debridement. A large thoracic defect usually results with subsequent exposition of heart, great vessels, aortocoronary bypass grafting, vascular prosthesis. Coverage with muscles transplantation was the standard procedure carried out in this series of 150 cases observed between 1983 and 1991. Details of technique are presented as well as a review of our reconstructive options. Rewarding results were observed even in the most challenging circumstances, suggesting that pursuing this aggressive approach was warranted. PMID- 1306425 TI - [Upper parietal pleurectomy with resection of bullae by thoracoscopy in spontaneous pneumothorax. New perspectives from preliminary results in 20 cases]. AB - In view of the increasing development of laparoscopic surgery and hoping to minimize thoracotomy's risks, we had the idea to perform pleurectomy as a treatment of Spontaneous Pneumothorax (S.P.) through video thoracoscopy. The operation was performed under general endobronchial anesthesia, the patient placed in the posterolateral thoracotomy position. Three trocars inserted through the 5th, 7th and 9th intercostal space, allowed the introduction of non specific thoracoscopic instruments similar to those used in laparoscopic surgery. The apical pleurectomy was delimited by the 6th rib, the internal thoracic vessels, the costovertebral sulcus and the first rib. Blebs and small bullae are now transected with application of the "EndoGIA 30". Pleural cavity was drained by F28 ans F32 tubes through the lower orifices. This procedure was performed in 18 patients presenting 20.S.P.. Operative indications were: persistent air link (7 cases), recurrence (9 cases), bullae with bridle and or anterior thoracotomy for S.P. (4 cases). One bleeding of 200 ml from a wounded intercostal vessel ligated with a clip was the sole operative hitch. Operative duration decreased from two to one hour. Average drainage duration was 3.5 dys and hospital stay 4.5 days. There was no death nor immediate complications. Post-operative pain was judged in all cases less intensive than that experienced after pleurectomy with thoracotomy. This original procedure is the first described as entirely performed through thoracoscopy with non specific instruments and hence economic impact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306426 TI - [Hepatobiliary complications of total parenteral nutrition]. AB - Total parenteral nutrition has showed his efficacy in severe digestive diseases. However, infections, metabolic and hepato biliary complications can appear. Aim of this study is to report hepato biliary complications in 200 adult patients, mean age 53 years, treated between 1979 and 1988. Three types of hepato biliary complications occurred in 138 patients initially free of hepato biliary disorders: 1) biochemical hepatic disorders (cholestasis and/or cytolysis) occurred in 58 patients (42%) with mean time of 27 days. In 40% these disorders disappeared after modifications or stop of parenteral nutrition. 2) Jaundice occurred in 9 patients (7%) with mean time of 73 days. Regression of Jaundice is possible only if enteral nutrition is reestablished. Sludge or cholelithiasis occurred in 34 patients (25%) with mean time of 43 days. In five of these patients cholecystectomy must be performed. Literature confirms high frequency of hepato biliary complications in total parenteral nutrition. Occurrence of these complications seems to be related to duration of total parenteral nutrition and to type of nutrition. Most complications decrease when we can stop total parenteral nutrition. Use of lipids in separated perfusion decreases significantly (p < 0.05) biochemical hepatic disorders occurrence. In conclusion, 1) biochemical hepatic disorders are very common, requiring biochemical hepatic tests weekly. 2) Jaundice is rare but serious, requiring stop of parenteral nutrition, and sometimes surgery to reestablish an enteral nutrition. 3) high frequency of cholelithiasis justifies ultrasonographic follow-up, and perhaps preventive cholecystectomy in operation leading total parenteral nutrition. PMID- 1306427 TI - [False anastomotic iliac aneurysms. How to detect them?]. AB - We report about 5 iliac anastomotic false aneurysms that occurred in 4 patients 8 to 21 years (average 15.5 years) after aortoiliac prosthetic reconstruction. The diagnosis was not established at once because of atypical clinical signs, in spite of the constant presence of an abdominal pulsating mass. All patients were operated by portal excision and graft replacement. One patient, who had presented with a hypovolemic collapse due to an acute rupture, died. The incidence of iliac false aneurysms after aortoiliac reconstructions is underestimated because the clinical surveillance is not reliable. The analysis of the explorations that were proposed led to prefer computed tomography to ultrasonography and angiography. The period of occurrence of iliac false aneurysms ranges between 6 to 10 years in average after the first operation. We therefore propose to perform a systematic follow-up CT examination on the 5th postoperative year, then every 5 years, and to operate the iliac false aneurysms as soon as their diagnosis is made. PMID- 1306428 TI - [Retro-costo-xyphoid hernia in adults. Apropos of 3 cases]. AB - Three cases of retrosternal diaphragmatic hernia (Morgagni hernia) are reported. Diagnosis have been made by conventional radiology (Chest X-ray, Upper G-I series) in 2 cases: the third one was found incidentally during a laparotomy. Peritoneography, CT scan, NMR are recommended in the difficult cases. ONe case presented as acute gastric outlet obstruction secondary to an intra-thoracic volvulus of the herniated stomach. Surgical treatment is indicated in all cases of retrosternal diaphragmatic hernia because of the high-risk of complications (gastric volvulus, colonic obstruction). Surgery through an abdominal approach is preferred and post-operative course is benign. PMID- 1306429 TI - [Approach to the hiatus and gastroesophageal reflux treatment by laparoscopic surgery]. PMID- 1306430 TI - [Failure to assist persons in danger in surgery]. AB - From 1949 to 1990, the authors gathered 120 files relating to 181 decisions, most of which are unpublished, and analyzed the teachings provided by case law about physicians faced with failure to assist persons in danger. This long series, extending over 30 years of application of article 63, paragraph 2, of the Penal Code--repressing failure to assist-, describes the most various conditions in which general practitioners or specialists were prosecuted, and most often charged and judged, by various criminal courts. In a number of cases, the appeals that were lodged enabled the Criminal Chamber of the Supreme Court to dram up Law rules taking primarily into account the strict application of the Penal Code article in cause, since its first decision in 1949. This article may involve surgeons as specialists, but also as "medical citizens" who are always regarded as having a particular mission of assistance, because of their vocation to rescue victims of accidents or patients in a pathological condition requiring assistance. The effectiveness of assistance is not considered in this legal requirement, which all representatives of the medical profession regard as a permanent sword of Damocles that must never be ignored whatever the circumstances and the practitioner's specialty. PMID- 1306431 TI - [Treatment of inguinal hernia by insertion of a subperitoneal patch under pre peritoneoscopy]. AB - From 1989 to 1991, 50 male patients presenting with reducible oblique lateral inguinal hernias were treated with a technique consisting in the insertion of a prosthetic Prolene patch (60 x 110 mm) interposed between the muscular wall and the peritoneal pouch. The prosthetic material was introduced and positioned anterior to the peritoneum using a laparoscope, after creating a pre- then a retropneumascos. This technique is a new application of non-invasive endoscopic surgery. PMID- 1306432 TI - [Early postoperative complications of resection anastomosis in colonic and colorectal surgery. An analysis of 624 cases]. AB - Six hundred twenty seven patients have been studied retrospectively to evaluate early complications after sewn or staples colonic anastomosis. Seventy four per cent of the patients underwent surgery because of malignant lesions and seventy seven per cent had an elective operation. Fourty seven per cent of the patients had a sewn anastomosis, 53% a stapled anastomosis. In elective surgery, most of the right hemicolectomies and partial proctocolectomies have been performed using stapler devices (p < 0.05). In emergency surgery, most of the anastomosis after partial and total colectomy have been hand sewn (p < 0.05). Operative mortality was 5.6%. It was significantly higher in older patients (> 80 years old) (p < 0.01) and after emergency operations (p < 0.0001). The rate of anastomotic leak was 3.7% and it was significantly higher after right hemicolectomy and partial proctocolectomies when anastomosis has been hand sewn compared to stapled anastomosis (p < 0.05). With regard to postoperative mortality, intra-abdominal abscess, intestinal obstruction, evisceration, pulmonary embolism and anastomotic stenosis 1.4% (global: after a 6 months follow-up) no significant differences have been observed between sewn and stapled anastomosis. PMID- 1306433 TI - [Complications of cholecystectomy by laparoscopic approach. Apropos of 6512 cases]. AB - 6,512 laparoscopic cholecystectomies have been performed by 141 surgeons. The lithiasis was uncomplicated in 80% of cases. Conversion from laparoscopy to laparotomy was necessary in 350 cases (5.37%), for technical problems (22 cases), complications (87 cases) or surgical difficulties (241 cases): 107 cholecystitis, 68 adhesions, 14 difficulties in finding the cystic duct and 25 common bile duct stones were the principle surgical difficulties. Among the 304 complications, we have observed 35 general and 251 local complications: 58 haemorrhages, 12 common bile duct lesions (10 cases of iatrogenic trauma and 2 accidental ligations), 4 cystic duct problems and 3 cases of intestinal trauma were the principle per laparoscopic complications. Among the 164 post-laparoscopies cholecystectomy's complications, we have observed 50 biliary fistulae with 32 requiring further surgery (damage to the common bile duct in 14 cases), 3 common bile duct strictures, 20 haemorrhages (7 requiring further surgery), 31 deep or sub-phrenic abscesses (16 requiring further surgery) and 2 peritonitis after intestinal trauma. We have had 7 deaths (0.10%). Prognostic factors are: 1) The degree of surgeon's experience; the first 50 laparoscopies cholecystectomies performed are more likely to require further surgery (P < 0.05). 2) Cholecystitis with an significantly higher rate of conversion to laparotomy (P < 0.001) and morbidity (P < 0.01). For an experienced surgeon the biliary morbidity is near to that observed in classical cholecystectomy. PMID- 1306434 TI - [An experimental study of the antitumor activity of tumor-infiltrating lymphocytes (TIL) in human tongue carcinoma in vitro]. AB - In the present paper tumor-infiltrating lymphocytes (TIL) from lymph nodes of human tongue carcinoma patients were obtained by discontinuous density gradients centrifugation and used in experimental treatment. The results showed that 1.3 x 10(8) TIL/g lymph node tissue were gotten by the above method. TIL activated by rIL-2 exhibited higher cytotoxicity to Tca8113 cell line than the same patient's LAK cells (81.48% and 24.69% respectively). There was significantly difference in the cytotoxicity between two groups (P < 0.01), indicating that TIL were the best source of adoptive immunotherapy. PMID- 1306435 TI - [Sagittal fracture of the mandibular condyle (SFMC): its clinical image diagnosis]. AB - Each of 12 SFMC patients (13 TMJs) underwent 8 X-ray examinations. It was found that SFMCs were easily missed from the conventional X-ray views, while CPMOT (Condyle pterygoid-maxillo oblique tomography) and CT were effective to demonstrate them. The reasons for SFMCs' being missed from the conventional views are discussed. It is concluded that the best procedure to show a possible SFMC is: the reversed Town's view-->TMJ coronal tomography or CPMOT-->CT (using coronal or CPMOT sections as the first choice). The authors declare that SFMC could not be explained by the acknowledged theory that the neck of condyle is a safety mechanism to protect the brain. PMID- 1306436 TI - [Effect of connective tissues underlying precancerous lesions combined with epithelia separated from normal mucosa]. AB - The connective tissues underlying the precancerous changes of the epithelia were separated and combined with the epithelia which were separated from the normal mucosa. The combinations were transplanted in nude mice. Specimens were taken at 6 and 10 weeks after transplantation and routinely processed for microscopic examination. The results show that the connective tissue underlying epithelial dysplasia may induce the normal epithelium undergoing epithelial dysplasia changes. The experiment demonstrates the etiological importance of the connective tissue in the development of cancer, and may be applied clinically in the treatment of precancerous lesions. PMID- 1306437 TI - [Stress distribution in the periodontal tissue around roots of an inclined abutment by 3-D photoelasticity]. AB - The stress distribution in the periodontal tissue around roots of a mesially inclined mandibular second molar as the the abutment of a fixed bridge was analysed by the three dimensional photoelasticity. It was shown by 3-D photoelasticity that the stress distribution in the alveolar bone around the roots of the abutment was modified by the placement of the fixed bridge. The maximum stress points in alveolar bone around the roots of abutment were also located. PMID- 1306438 TI - [The relationship between phonetics and palatal rugae of complete denture]. PMID- 1306439 TI - [Clinical application of antidromic angiography through external jugular vein]. AB - Antidromic angiography through external jugular vein could show the real appearance, limits and reflux veins of cavernous hemangioma. Pathologic changes in venous system were shown with this method. It is a simple and the best method in diagnosing deep and larger cavernous hemangioma which is hard to treat agent. It plays also a role in differential diagnosis of some cystic mass with intracapsular blood. It is also better than tumor cavity angiography. PMID- 1306440 TI - [The causes of longitudinal fracture of the upper complete denture base]. AB - Laying the strain gauge on the design areas of palatal base and frenum labiorum of complete dentures and simulating the different shapes of notch of frenums by the photoelastic mould. The test of the base condition under static and dynamic load by electrical measurement method was carried out. The longitudinal breaking line on the front part of the palatal base was first observed. The causes of breaking may be due to: the weak effect of notch of frenum labiorum; stress concentration on the front part of the base; material fatigue caused by the repeated alternate force and the strength of base material reduced by unsuitable processing. PMID- 1306441 TI - [The distribution of glycosaminoglycans in the temporomandibular ligament]. AB - The distribution of glycosaminoglycans (GAGs) in the adult dog's Temporomandibular ligament (TML) was studied by histochemical methods. Two staining methods were used, Alcian blue/PAS and Alcian blue with different concentration of MgCl2 (the Critical electrolyte concentration (CEC) method). It was found that GAGs were mainly localized in the TML, especially in the ligamental midsubstance and condylar attachment area, rather than in the capsule. Various GAGs distributed differently between the TML and capsule and they were also different among the different parts of the TML, although the majority of the CEC values was found corresponded to those of Chondroitin/Dematan Sulfate. It was suggested that the different topographical distribution of GAGs between the TML and capsule was probably related to their structure and function. PMID- 1306442 TI - [The application of nasometer on the analysis of normal and cleft palate speech]. AB - This paper reports the use of for assessment of speech by oronasal acoustic measures. Nasal energy during speech is reflected by nasolance value and graph pattern. The degree of velopharyngeal closure and the situation and movement of other speech organs can be demonstrated. The speech of 120 normal children and 60 preoperation cleft palate patients are studied. The scales of normal value and graph pattern are recorded. Comparing with normal speech, the scale of nasolance value and characteristics of graph pattern of cleft palate speech are obviously changed and may be assessed by this apparatus. The treatment and speech therapy plan can be made with the results obtained by this method as the basis. PMID- 1306443 TI - [The experimental research on the changes in the amount of prostaglandins in rat alveolar bone during tooth movement]. AB - In this paper, the author observed that in different time the changes of the amount of endogenous prostaglandins in rat alveolar bone under continuous orthodontic force, and confirmed that there are certain amount of PGE1. PGE2 in the rat alveolar bone even without orthodontic force, and the amount is no difference between right and left side. After several hours when the orthodontic force was applied the amount of PGE1 and PGE2 in rat alveolar bone rose significantly. But it is transient and does not last 24 hours. PMID- 1306444 TI - [Clinical application of positioner and its fabrication]. AB - Positioner is one type of removable appliances made of elastic material. This material, which is a kind of high polymer and has recoverable ability, may be as a new type of orthodontic material used not only in orthodontic treatment of various kind of malocclusions but also in retention in later stage of treatment. It is not same to the stainless steel wire of traditional removable appliances which must be activated every time to produce a little tooth movement. The advantages of positioner are to reduce the visit frequency and to shorten the duration of treatment. According to our clinical experiences, the indications are: simple individual malocclusion; treatment and retention in later stage of various kind of malocclusions; and patients who couldn't come to clinic regularly. PMID- 1306445 TI - [Experimental study and evaluation of pulpotomy with hydroxyapatite]. PMID- 1306447 TI - [Lectin histochemical studies of oral leukoplakia]. PMID- 1306446 TI - [The effect of berberine in sterilizing infective root canal of deciduous teeth]. AB - This investigation introduces the effect of sterilizing infective deciduous root canal with Chinese traditional herb berberine. Through the bacterial test, animal test, clinical practice, and comparing with the dental root disinfectant for mocresol (FC) and comphorphenol (CP) it indicates that berberine Chinese traditional herb is a excellent disinfectant for infective deciduous root canal. PMID- 1306448 TI - [A concept of retruded closed position of edentulous jaws and its significance]. PMID- 1306449 TI - [Analysis on the risk factors of caries with conditional logistic regression model]. PMID- 1306450 TI - [Electrophysiological effects of intravenous propafenone for treating atrial ventricular nodal dual pathways reentrant tachycardia]. AB - The acute electrophysiological effects of intravenous propafenone were studied through programmed electrical stimulation in 9 patients with atrio-ventricular nodal dual pathways reentrant tachycardia (AVNDP-RT). The results showed that propafenone prolonged significantly the effective refractory period of atrial ventricular nodal fast pathway (AVN-FP) in retrograde conduction and might further terminate the paroxysmal supraventricular tachycardia (PSVT). It is an effective drug for treating AVNDP-RT. Neither blood pressure dropping nor other side effects were observed. PMID- 1306451 TI - [A comparative study of coronary arteriography and myocardial emission computed tomography in the diagnosis of coronary heart disease]. AB - Both coronary arteriography (CAG) and myocardial emission computed tomography (ECT) were performed in 58 patients. According to CAG findings and clinical manifestations, 47 patients were diagnosed as coronary heart disease (CHD), while 11 not. CAG was abnormal in 39 patients of the 47. The sensitivity and specificity of CAG were 83% and 100% respectively. The diagnosis of CHD was made without any doubt in patients with abnormal CAG. The sensitivity of ECT was 97.9%, the specificity only 45.5%, and the predictive value of negative ECT 83.3%. Therefore, abnormal ECT should be closely related to the clinical manifestations in order to evaluate its significance and a normal ECT may rule out CHD with more reliability. PMID- 1306452 TI - [Noninvasive estimation of the pulmonary artery pressures in patent ductus arteriosus with continuous-wave Doppler echocardiography]. AB - To develop a new method for noninvasive measuring of the pulmonary artery pressure (PAP) in patient ductus arteriosus (PDA), left and right heart catheterization (Cath) and continuous-wave Doppler echocardiography (CWD) were performed simultaneously in 30 cases with PDA. The results showed that there was high correlation of the systolic peak pressure gradient (delta pp), the end diastolic pressure gradient (delta Pd) and the mean pressure gradient (delta Pm), across PDA measured with the two techniques (r = 0.99, 0.96 and 0.98, respectively). The CWD-derived pulmonary artery systolic (PASP), diastolic (PADP) and mean (PAMP) pressure, which were estimated by subtracting delta Pp, delta Pd and delta Pm from the brachial artery systolic, diastolic and mean pressure, correlated well with the corresponding PAP measured with Cath (r = 0.92, 0.89 and 0.94, respectively). It is concluded that CWD offers a reliable technique for estimating shunt pressure gradients and PAP in patients with PDA. PMID- 1306453 TI - [Potentiated polarized liquid therapy and heart emergency]. AB - Kalium and Magnesium ions are important cations in human body, both of them take part in many processes of metabolism in coordination. Injection of Kalii L aspartatis and Magnesii L-aspartatis added to polarized liquid (GIK-Glucose, Insulin, Kalii Chlorid) might potentiate its effect and reduce carbon dioxide and ammonia in blood. 72 patients with various heart emergencies and other critical diseases were treated with potentiated polarized liquid (GIKL) with remarkable efficacy. A preliminary study on its clinical use and mechanism was carried out. PMID- 1306455 TI - [Measurement of gastric emptying in non-ulcer dyspepsia]. AB - Using real-time ultrasonography, we monitored gastric emptying indirectly in 26 cases of non-ulcer dyspepsia (NUD) and 13 healthy adults by determining the anteroposterior gastric measurement of a single section of the stomach in the corpus fundus immediately after drinking 500 ml water and then every 10 min. for five times. The average time for 50% gastric emptying in NUD patients (36.46 +/- 13.13, x +/- s) was longer than that in healthy adults (23.54 +/- 5.93), but the half time of gastric emptying in male with NUD was not significantly different as compared with that in male controls and female patients of NUD. PMID- 1306454 TI - [Obstructive sleep apnea syndrome and essential hypertension: diurnal variation of urinary catecholamines]. AB - 30 subjects of old and middle age (28 male, 2 female) with obstructive sleep apnea syndrome (OSAS) and 20 normal subjects with matchable age and body weight (14 male, 6 female) as control were studied with nocturnal polysomnography for at least 7 hours. Right arm blood pressure was determined in supine position before and after sleep. Meantime, three 8-hour urine specimens, two collected while awake and one during sleep were examined for urinary levels of epinephrine (E) and norepinephrine (NE) with fluorometric method. All OSAS subjects (mean apnea index 42.9) had significant arterial oxygen desaturation (mean 63.9%). 12/30 OSAS subjects had definit history of essential hypertension. They described that hypertension appeared months or years after the onset of sleep disorders. Before sleep the blood pressure in OSAS subjects was higher than that in controls (mean 133/90 mmHg versus 118/77 mmHg P < 0.001). After 7 hours of sleep with apnea events, the blood pressure rose to 149/100 mmHg (P < 0.001). whereas in the controls there was no change of statistic significance (mean 115/77 mmHg). A diurnal rhythm in free catecholamines excretion was apparent for both NE and E (P < 0.05) in the controls, while in OSAS there was no normal diurnal rhythm. 24 hour values of NE were remarkably higher than those in controls. It is known that up to 40% of OSAS subjects is in the population of essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306456 TI - [Hepatocyte stimulatory peptide and its clinical significance in viral hepatitis]. AB - Hepatocyte stimulator peptide (HSP) is a new hepatic stimulator substance. Its monoclonal antibodies have been obtained in our laboratory. In this study, HSP was determined in the sera of 315 subjects including patients with various forms of hepatitis and healthy persons with enzyme-linked immunosorbent assay (sandwich method). It is shown that HSP level in the sera of patients with fulminant hepatitis was high and correlated with the level of tumour necrosis factor (TNF), serum bilirubin (SB) or prothrombin time (PT). It is suggested that level of HSP in the sera of the patients reflected the degree of hepatocyte injury. A formula was recommended to predict the outcome of the patients with fulminant hepatitis. PMID- 1306457 TI - [Hepatitis B virus DNA in the serum of anti-HBs positive persons]. AB - In order to investigate the significance of HBV DNA in the serum of anti-HBs positive persons, the serum of 76 anti-HBs positive persons was studied for HBV DNA by means of polymerase chain reaction (PCR). The results showed that 21 (32.2%) out of 65 cases without hepatitis B vaccination were positive for HBV DNA detected with PCR (PCR-HBV DNA), but no one was positive for PCR-HBV DNA in 11 cases inoculated against hepatitis B. It was also found that 6 cases were positive for HBsAg-Ab immunocomplex in those positive for PCR-HBV DNA and the liver tissue in 2 of the 5 cases with liver-biopsy were positive for HBVAg determined with immunohistologic ABC method. We believed that persons, who acquired anti-HBs after HBV infection were different from those who were vaccinated, might carry HBV which come from the HBsAg-Ab immunocomplex and HBVAg positive hepatocytes. In addition, the study also proved that the PCR-HBV DNA positive rate correlated significantly with the anti-HBe and or anti-HBc positive rate and with the abnormal rate of liver function in the anti-HBs positive persons. It was suggested that persistent presence of HBV DNA in the bodies should be responsible for the persistent presence of anti-HBe and anti-HBc in the serum and also for the liver damage. PMID- 1306458 TI - [Factors related with stroke recovery]. AB - 81 patients with an average of 61 who had a hemispheric stroke for the first time and survived more than 12 months were followed in order to study the factors related with recovery. The results are: (1). The severity of the initial attack and the presence of depression and other complications in recovery period are the main relating factors with both the quality of life and recovery of neurological deficits. (2). The size of the lesion shown in CT is the main relating factor with the recovery of neurological deficits. (3). function of affected hand is a main relating factor with the quality of life. According to these results, it is essential to have a preliminary consideration to facilitate recovery at the initial stage of stroke and to organize the rehabilitation programs for the patients. PMID- 1306459 TI - [Application of serum somatomedin C level to assess the disease activity in patients with acromegaly]. AB - Serum SMC level was measured in acromegalic patients with different disease activity. The serum SMC level of 10 untreated and 15 treated patients with active disease was 30.5 +/- 17.6 and 23.8 +/- 16.3 KU/L respectively. These levels were significantly higher than the value 2.7 +/- 2.8 KU/L in 7 patients during remitting state. The serum SMC level correlated with the basal and the nadir GH level and the area under the GH curve in glucose suppression test. The serum SMC levels in 6 patients with prolactinoma, 10 patients with Grave's disease and 8 patients with renal failure were all in normal range, but in 10 patients with liver cirrhosis it was 0.36 +/- 0.39 KU/L, which was significantly lower than the normal value. We concluded that serum SMC level is a good criterion for assessment of disease activity of acromegaly for it does not require a dynamic test and it does not increase in other diseases. PMID- 1306460 TI - [Molecular pathology of inherited Glanzmann's thrombasthenia. Report of 11 cases]. AB - Glycoprotein IIb-IIIa (GPIIb-IIIa) concentration was studied in 11 patients with Glanzmann's thrombasthenia (GT) with sensitive Western blotting technique. 7 patients with severe GPIIb-IIIa deficiency (less than 10% of the normal) were designated as type I (64% of patients), 2 patients with moderate GPIIb-IIIa deficiency (10-25% of the normal) as type II (18%) and 2 patients with GPIIb-IIIa 40-100% of the normal as variants (18%). Southern Blotting was used to analyze the GPIIb and GPIIIa genes in the 11 patients. The results showed that there were no major deletions or insertions in either the GPIIb or GPIIIa genes. However, a small change in GPIIb gene was demonstrated in two sibling patients and the abnormality of GPIIIa gene was found in another two patients. These observations combined with those from literature provide a basis for discussing the molecular pathology of Glanzmann's thrombasthenia. PMID- 1306461 TI - [The advances in the treatment of chronic hepatitis C with interferon]. PMID- 1306462 TI - [Analysis of the therapeutic effect of radial keratotomy]. AB - 666 cases (1,302 eyes) of myopia were performed radial keratotomy and 738 eyes were followed up for 6-9 months. Before surgery, the mean spherical refraction was -6.65D and the mean keratometry was 44.17D with uncorrected visual acuity of 0.03-0.4. 6-9 months after operation, the mean spherical refraction decreased by 4.76D, or an average decrement of 2.69D for mild myopia, 4.07D for moderate myopia, 5.28D for high myopia, and 6.00D for very high myopia. The percentages of eyes with postoperative uncorrected visual acuity > or = 0.5 were 100%, 84.86%, 58.01% and 20.59% for mild, moderate, high and very high myopia respectively, and the corresponding figures for postoperative uncorrected visual acuity > or = 1.0 were 89.29%, 55.71%, 17.79% and 3.92% respectively. Complications were few. PMID- 1306463 TI - [Radial keratotomy for the treatment of myopia]. AB - 210 eyes were performed radial keratotomy for treatment of myopia of mean -5.65D. The central clear zone was 3mm-4mm in diameter, and 4, 6, 8 or 12 incisions were made. The depth of cut was estimated at 90%-95% of the corneal thickness. After a mean follow-up of 15.4 months, myopia was reduced by an average 4.99D, keratometric corneal refractive power by 3.91D, and 42.4% of the eyes became emmetropic. The complications included corneal microperforation in 4.3%, visual fluctuation in 36.2%, glare in 11.9%, overcorrection from +0.75 to +1.50D in 3.8%, and undercorrection from -1.00 to -5.25D in 20.0% of the eyes. The rate of endothelial loss averaged 5.9% in the central and 6.0% in the peripheral area of the cornea. PMID- 1306464 TI - [An analysis of the causes of glaucomatous visual function damage by computed multifactorial stepwise regression]. AB - Computed multifactorial stepwise regression analysis of quantitative visual field deterioration in relation to 28 factors showed that only the hemorheological indices entered the multiplex regression equations, especially accurately for POAG patients with severe visual damages. Besides, the patients might also have lower antioxidant capability in the red cell membrane protein. Based on the present results and data abroad, POAG might pertain to the blood hyperviscosity syndrome, and with elevated intraocular pressure and decreased ocular arterial pressure, the visual function damage would be aggravated. PMID- 1306465 TI - [Quantitative computerized image analysis of the relationship between neovascularization and nonperfusion area in branch retinal vein occlusion]. AB - Quantitative computerized image analysis of composite fluorescein angiograms of 62 eyes with branch retinal vein occlusion (BRVO) found 33 eyes with newly formed blood vessels. Determination of the ratio of the retinal capillary nonperfusion area to the disk area revealed that the ratio was positively correlated with the incidence of neovascularization, in that 10.0% of the cases with the ratio under 10 and 63.2% of the cases with the ratio between 10-30 had neovascularization, and the incidence of the latter increased to 82.6% among cases with the ratio over 30. The calibres of 344 retinal arteries and veins in normal subjects and in the affected and unaffected eyes of BRVO patients were measured to find that both vessels were narrowed in late patients of retinal vein occlusion. PMID- 1306466 TI - [Assessment of the panel D-15 and FM 100-hue tests for the detection of congenital dyschromatopsia]. PMID- 1306467 TI - [Contrast sensitivity in the fellow eye of unilateral age-related macular degeneration]. AB - The VCTS 6000 Contrast Sensitivity Test System was used in testing the fellow eyes of 20 cases of unilateral age-related macular degeneration (ARMD), with age matched normal controls. Among the patients, 25% of the fellow eyes showed minor contrast sensitivity reduction at medium and high spatial frequencies. This test may be useful in the diagnosis of subclinical ARMD. PMID- 1306468 TI - [Strabismus and stereopsis in children]. AB - 43 strabismus children 5-12 years old were successfully corrected with surgery plus synoptoscope functional training before and after the operation. They were followed up for an average 2 years: 38 cases (88.4%) obtained qualitative stereopsis with the synoptoscope, and 14 cases (32.6%) obtained central stereoacuity with Yan's stereoscopic test charts. The results indicated that early surgical intervention plus functional training before and after the operation was an effective means to raise the functional cure rate of strabismus in children. The two methods of synoptoscope and Yan's stereoscopic test charts and their clinical significance were discussed. PMID- 1306469 TI - [An analysis of 12 cases of ocular acanthoma]. AB - The series of 12 cases of acanthoma comprised 6 males and 6 females, aged 29-62 years, averaging 45 years. The duration of disease was 1-4 months, and the lesions were located on the upper lid (3 cases), the lower lid (4 cases), the inner canthus (1 case), the corneal limbus (2 cases), and the palpebral or bulbar conjunctiva (1 case each). 9 lesions grew to be masses, with central umbilication or ulceration in 3 cases each. After local excision, 7 cases were followed up 2 months to 9.5 years and none relapsed. PMID- 1306470 TI - [A clinical study of primary lipoma and liposarcoma of the orbit]. AB - 3 cases of primary lipoma and 2 cases of liposarcoma originating from the orbit were confirmed histopathologically. The clinical features, pathologic findings, ultrasonography, computed tomography, and nuclear magnetic resonance imaging of the tumours and the differential diagnoses were discussed. PMID- 1306471 TI - [Microbiology of soft contact lens-related keratitis]. AB - Among 385 specimens of presumed microbial keratitis cultured at Beijing Institute of Ophthalmology from April 1988 to December 1990, 21(6%) were associated with extended-wear contact lenses. Of the latter, 10(48%) were cultured bacterio positive, including 8(80%) of gram-negative and 2(20%) of gram-positive bacteria. Pseudomonas aeruginosa was found in 6 specimens, accounting for 60% of the bacterio-positive cultures. In the meantime, among the 364 specimens not associated with contact lens wear, 87(24%) were cultured positive, including 27(31%) of gram-negative bacteria, 32(37%) of gram-positive bacteria and 20(23%) of fungi, while mixed cultures and nocardia each accounted for 4(5%). 9 contact lens containers and all cleaning solutions of 11 cases of pseudomonas corneal ulcers were cultured to find them 100% positive of P. aeruginosa. PMID- 1306472 TI - [Analysis of 7 elements in the serum and lens of senile cataract patients]. AB - The contents of Fe, Al, Cu, Zn, Ca, Mg and P in the serum and lens of senile cataract patients were determined with inductively coupled plasma (ICP) spectrometry to find that (1) the Fe, Al, Zn and Ca levels in senile cataractous lenses were significantly higher, and the P level lower than those in normal subjects; however, the serum levels of Fe, Al, Zn and Ca were significantly lower, and the level of P higher than those in normal subjects; (2) the serum levels of Cu and Zn varied with the duration of cataract, which could explain the inconsistency among authors with regard to these parameters; (3) the relation between Fe and Al and the development of cataract remained to be elucidated; (4) the Ca/P ratio in senile cataractous lenses was 50 times (1:0.02) that in clear lenses; these 2 elements were regarded to have close relation with cataractogenesis; and (5) Cu and Mg were not related to cataractogenesis, a finding in agreement with most reports. PMID- 1306473 TI - [Uveitis and immune complexes]. AB - The mean level of circulating immune complexes (CIC) in 24 uveitic patients determined by PEG deposition with the biochemical analyzor was found to be 28.458 +/- 7.796, in contrast to the value of 14.499 +/- 6.194 in the control group. The CIC level in acute iridocyclitis and panuveitis was significantly elevated compared with those in other types of uveitis. The results again demonstrated that most cases of uveitis, especially those of unknown origin, were related with immune complexes, and changes in the level of CIC could also be an indicator of therapeutic effects. PMID- 1306474 TI - [A study on the diametric growth of the cornea in Chinese children]. AB - The horizontal and vertical diameters of both eyes were measured with Wissly's keratometer in 65 children under 3 1/2 years of age and in 65 normal adults. The results showed that the human cornea continued to grow after birth until end of the 3rd year. PMID- 1306475 TI - [An epidemiological survey of blindness and low vision in Shandong Province]. AB - An epidemiological survey of blindness and low vision was carried out in a sample population of 115 167 in Shandong Province to find that the prevalence of binocular blindness was 0.34%, that of unilateral blindness 0.65%, that of binocular low vision 0.46%, and that of unilateral low vision 0.64%. The prevalence rates increased with age and the leading causes of blindness, in order of importance, were cataract, corneal diseases and glaucoma in urban areas, and cataract, corneal diseases and retinal diseases in rural areas. PMID- 1306476 TI - Disc and field damage in patients with unilateral visual field loss from primary open-angle glaucoma. AB - To assess the temporal relationship between field and disc change in early glaucoma, 24 patients with unilateral visual field loss from primary open angle glaucoma were identified for planimetric optic disc measurements. Cross-sectional analysis of disc rim area was performed and compared to 25 age-matched normal controls. The mean (+/- SD) disc rim area in eyes with normal visual fields (1.10 +/- 0.31 mm2) was slightly larger than that of eyes with visual field loss (0.90 +/- 0.33 mm2). The mean disc rim area in the control group (1.49 +/- 0.19 mm2) was significantly different from both sets of eyes in the asymmetric primary open angle glaucoma patients (p = 0.000). These findings support the hypothesis that loss of the optic disc rim can be detected before perimetric abnormalities develop in patients with glaucoma. PMID- 1306477 TI - Monitoring in vivo lens changes. A comparative study with biochemical analysis of protein aggregation. AB - In this study the AA attempted to evaluate the relationship between lens optical density and lens fluorescence determined in vivo, with some specific (in vitro) biochemical changes occurring during cataract development. Special attention has been given to the comparison between diabetic and non diabetic cataracts. Prior to surgery all lenses were analysed by Scheimpflug photography to evaluate the topography of opacities and fluorescence distribution. Individual lenses were separated into cortex and nucleus and the amount of high molecular weight (HMW) protein aggregates was determined by FPLC (Fast Performance Liquid Chromatography). The results found in this study have shown that, as it would be expected, diabetic cataractous lenses present higher fluorescence levels than senile cataracts. It has also been shown that the increase in lens optical density, determined by Scheimpflug photography is clearly related to the increase in the amount of HMW-aggregates. Furthermore, in diabetic cataracts, a good correlation between protein aggregation and lens fluorescence determined in vivo has been found. Thus, it seems that in diabetic cataracts chemical or metabolic mechanisms leading to the production of fluorescent chromophores may be related to protein aggregation and therefore to the major processes involved in cataract development. PMID- 1306478 TI - Simulating age-related optical changes in the human eye. AB - The decline in visual function observed in older adults has been attributed to a deterioration in optical quality, decreased neural function, or a combination of both of these factors. One way of separating their contribution is to design a simulation of the optics of the elderly eye and examine its effect on the visual performance of younger observers. The age-related reduction in pupil size was simulated by the administration of an ophthalmic miotic drug, whilst a neutral density filter was included to account for the increased absorption of the ocular media. An optical cell containing a critical concentration of 500 nm diameter polystyrene microspheres in suspension was used to simulate light scatter. The spatiotemporal contrast sensitivity of an older group of observers was then compared with that of a younger group with and without the optical simulation. The contrast sensitivity of the younger group was consistently better than that of the older, and the presence of the optical simulation produced no significant effect on performance. This suggests that, under normal viewing conditions, it is primarily neural factors which underlie the deterioration in visual quality experienced by older observers. PMID- 1306480 TI - Effect of the application of acetazolamide soaked contact lenses on intraocular pressure of rabbits. AB - Topical application of acetazolamide has no known effect on intraocular pressure (IOP). We tried to detect the hypotensive effect on IOP of acetazolamide soaked onto soft contact lenses (CL). We applied CLs soaked in either 1%, 3%, or 5% acetazolamide solution onto one eye of 29 rabbits while the contralateral eye served as a control. There was an average 32% reduction of IOP amongst all acetazolamide applied eyes, and an average 19% reduction of IOP amongst all control eyes. Amongst the 1% acetazolamide-CL applied eyes there was a mean 37% reduction of IOP, amongst the 3% acetazolamide-CL applied eyes a mean 36% reduction, amongst the 5% acetazolamide-CL applied a mean 30% reduction, and a mean 19% reduction in control eyes. The longest period of IOP reduction followed the application of 1% acetazolamide-CLs, probably owing to improved drug corneal penetration at this concentration. Our results reveal that the application of acetazolamide soaked soft CLs has a significant hypotensive effect on IOP in both the applied and contralateral control eyes of rabbits. PMID- 1306479 TI - Field loss after pan retinal photocoagulation with diode and argon lasers. AB - Argon and diode laser pan retinal photocoagulation are used in diabetic proliferative retinopathy. This is a prospective study of the effects of each laser type on peripheral field loss. It shows that diabetics have significantly reduced peripheral field prior to laser compared to normals (p = 0.006). With identical pan retinal photocoagulation with either argon or diode laser there is no difference in field loss. PMID- 1306481 TI - Results of extracapsular cataract extraction with lens implant. A review of 1625 cases. AB - We studied the results and complications of extracapsular cataract extraction with lens implantation. A one year follow-up of 1625 cases is described. PMID- 1306482 TI - Induced astigmatism following small incision cataract surgery combined with trabeculectomy. AB - The combination of phacoemulsification and implantation of foldable intraocular lenses through a small incision with a trabeculectomy is increasingly preferred in glaucoma patients with coexisting cataract. Small incisions induce less astigmatism and thereby enhance visual recovery. This study should clarify if this benefit of small incision cataract surgery is preserved when combined with a trabeculectomy. Thirty-five eyes were included in this study. Preoperative astigmatism measurements were compared with those obtained one month and one year postoperatively. Vector analysis was performed. A series of 30 cases which underwent small incision cataract surgery alone were used as a control group. One month postoperatively the eyes undergoing the combined procedure showed about the same with-the-rule astigmatic peak (mean: +0.32 dpt.) as the control group eyes (mean: +0.26 dpt.; p > 0.05). One year postoperatively both groups showed the same against-the-rule astigmatic shift (mean: -0.28 dpt.; p > 0.05). In conclusion, patients undergoing small incision cataract surgery combined with trabeculectomy showed a small amount of surgically induced astigmatism. When compared with patients which underwent small incision cataract surgery alone, the difference in astigmatic changes was found to be statistically not significant. PMID- 1306483 TI - Visual impairment in hysteria. AB - We have reviewed the charts of 45 neuro-ophthamological patients diagnosed with 79 monocular visual field or visual acuity losses secondary to non-organic etiology. Our aim was to determine the percentage of patients that have improvement in vision. As part of the protocol, all patients had magnetic resonance images, pattern visual evoked potentials, and flash electroretinography in addition to complete neuro-ophthalmological examinations. A single physician performed both the initial and follow-up examinations of all patients. Thirty three percent of these patients had visual field defects only, 62% had both visual field defects and visual acuity defects, and 5% had only visual acuity defects. After organic disease was ruled out, all were given a timetable for recovery and clear reassurance regarding their prognoses for visual recovery. Seventy-eight percent of these patients showed improvement or were normal, while 22% showed no improvement. Younger patients without obvious psychiatric disorder had better prognoses than older patients. PMID- 1306484 TI - Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson's disease. AB - Two patients with advanced Parkinson's disease were followed for 6 months before, and 18 months after, receiving stereotaxic grafts of fetal mesencephalic tissue from aborted human fetuses. Parameters studied included a series of standardized tests of movement, response to levodopa, electrophysiological recording of the motor readiness potential, and positron emission tomography (PET) with ligands based upon levodopa and upon the dopamine reuptake inhibitor nomifensine. The patients each received stereotaxic implantation of ventral mesencephalic tissue containing midbrain dopamine neurons from aborted human fetuses of 8 to 10 weeks gestational age into the caudate and putamen of one hemisphere. Throughout their 18-month course, the patients were treated with cyclosporine, azathioprine, and glucocorticoids to minimize the risk of graft rejection. There were no significant complications from the procedure, but there was also no major change in their assessment of impairment on the Hoehn and Yahr scale. However, significant changes were observed in clinical, electrophysiological, and PET measures. Changes in these parameters, apparent at 6 months postoperatively, were described in detail in a previous report. The purpose of this present report is to provide follow-up data from the subsequent year with an emphasis on longitudinal evaluation methodology. Standardized clinical testing showed a small but long-term improvement in the first of the two patients. Following the operation, she was able to walk in "off" periods, which she had not been able to do preoperatively. This improvement was accompanied by increased walking speed and reduction in the time necessary to perform a series of pronation and supination movements using both hands. Although these improvements have continued throughout the postoperative period, they have not alleviated her basic neurological impairment. The second patient showed similar improvement during the first 6 months; she then reverted to her preoperative status at the end of the 18 month follow-up period. The electrophysiological recordings were consistent with the clinical findings. Both patients had significant changes in the motor readiness (bereitschafts) potential amplitude, which was greatest 5 to 7 months postoperation. The amplitude of the potential declined subsequently for both patients, but remained significantly elevated over the preoperative baseline for patient 1. The analysis of the PET scans was somewhat compromised by technical problems in the preoperative scans. However, they are also consistent with the clinical data. In comparisons of the operated and the unoperated sides, fluoro dopa showed increased uptake in the caudate nucleus of patient 1 at 6 months and at 13 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306485 TI - Regional expression of fos-like immunoreactivity following seizures induced by pentylenetetrazole and maximal electroshock. AB - The expression of fos-like immunoreactivity (FLI) has been used widely as a marker of neural activation following the induction of seizures in several experimental models of epilepsy. The purpose of the present study was to provide a more detailed regional analysis of FLI expression following the induction of seizures by maximal electroshock (MES) and pentylenetetrazole (PTZ). Tonic-clonic seizures, matched for duration, were induced by MES applied by earclips (40 mA, 1 s) and intraperitoneal injections of PTZ (60 mg/kg); tonic hindlimb extension was present only after MES. Two hours after the induction of seizures brain tissue was processed for FLI. High levels of FLI were induced by both convulsion inducing processes in a range of structures, including the dentate gyrus, the caudal amygdala, parts of the cerebral cortex, the bed nucleus of stria terminalis, various thalamic nuclei, the lateral parabranchial nucleus, and the nucleus of the solitary tract. In other structures, such as the medial and rostral amygdala, the ventromedial hypothalamic nucleus, the peripeduncular area, the central gray, and parts of the pretectum and superior colliculus, significantly greater FLI was induced by MES. Only in relatively few structures, such as the reticular thalamic nucleus and arcuate nucleus of the hypothalamus, did PTZ cause a much larger expression of FLI than MES. Insofar as the c-fos technique reflects neuronal activation, the present data reveal potentially important differences in the circuitry underlying the seizures induced in two major experimental models of epilepsy. PMID- 1306486 TI - Immunochemical studies of extracellular glycoproteins (X-GPs) of goldfish brain. AB - Exoglycoproteins (X-GPs) are a family of soluble glycoproteins which are the most prominent constituent of the extracellular compartment of goldfish brain. On conventional two-dimensional polyacrylamide gels they typically display two primary molecular weight forms, averaging about 33 and 38 kDa, each appearing as a row of five to seven individual spots. When X-GP antibodies were applied by Western blotting, gels of goldfish brain extract prepared without a reducing agent showed, in addition to the primary molecular weight groups, at least one row of spots of slightly lower molecular weight and a major array of spots in the range of 45-60 kDa. The latter presumably represent dimers of the primary X-GP forms since they gave rise to the primary forms upon treatment with a reducing agent. However, on gradient gels prepared without detergents or reducing agents, X-GPs identified by immunostaining appeared only at 200 kDa and above, indicating that these proteins naturally occur in the form of large particles. Deglycosylation of the brain extract by N-glycosidase F reduced the molecular weight of each primary X-GP form by about 5 kDa, but did not abolish the microheterogeneity, which is at least partly due to minor differences in primary structure among the proteins in individual spots. Both rows of spots in the deglycosylated sample showed a coordinated shift toward the basic side of the gel, and a prominent new spot appeared on the basic end of the lower molecular weight group, which probably represents the fully deglycosylated form of the most abundant X-GP isoform.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306487 TI - Reinnervation of denervated skeletal muscles by grafted dorsal root ganglion. AB - We examined whether or not the cervical dorsal root ganglion (DRG) of the rat, when isografted and connected to the distal stump of the severed common peroneal nerve, could survive, project axons to the denervated leg muscles, and exert beneficial influences to delay the degeneration of the denervated muscles. Rats in which the muscles were similarly denervated but no DRG was grafted served as the control. After a postoperative period of 72 to 286 days, histological study showed that nerve cells at the superficial part of the grafted DRG survived. Indirect electrical stimulation via the distal stump of the common peroneal nerve produced no contraction of the muscles, indicating that no functional neuromuscular contacts had been reestablished. Direct stimulation of the denervated muscles did elicit contraction, and the isometric twitch and tetanic tensions were significantly much higher in the experimental rats with a grafted DRG than in the control rats. Cholinesterase-silver staining indicated the presence of axons in the denervated muscles, but the axons did not terminate on endplates. Compared with the control muscles, the experimental muscles had significantly more axons, and had atrophied less as indicated by muscle wet weight and histological appearance. These results indicate that the sensory axons can delay the weakening and atrophy of muscles after denervation. We suggest that the sensory axons may exert certain trophic influence on the denervated muscle fibers, though the actual mechanism is unknown. PMID- 1306488 TI - Neurotoxic components in normal serum. AB - Serum neurotoxicity was studied by adding whole or fractionated serum (adult human, adult horse, or newborn calf) to neuron-rich cultures prepared from various regions of embryonic (Days 14-15) rat brain, including spinal cord, ventral mesencephalon, cerebellum, septum, and striatum. Effects of serum were also tested on several types of embryonic non-neuronal cells (skeletal muscle myotubes, cardiac muscle myocytes, and fibroblasts from skin and lung). Serum concentrations of 50% or more killed more than 95% of all neurons within 3 days. Serum concentrations as low as 10% also killed some neurons, especially those from cerebellum. Septal, cerebellar, and spinal cord neurons were more sensitive than striatal or mesencephalic neurons. All the tested non-neuronal cells survived much better than neurons at serum concentrations of 20% or more. Neurotoxicity was present in both fresh (human) and previously frozen (human and animal) sera, and affected both young (4 days in vitro) and older (42 days in vitro) cultures. Neurotoxicity was greatly diminished by heating the serum to 56 degrees C for 30 min. Experiments indicated that serum toxicity was not due to lipoprotein, complement, or tumor necrosis factor. All serum neurotoxicity was retained by an ultrafilter with a nominal molecular weight cutoff of 10 kDa. The profile of neurotoxicity following gel filtration at neutral pH was variable, with high toxicity most consistently observed in fractions with apparent molecular weights exceeding 100 kDa, and variable degrees of toxicity at lower molecular weights. PMID- 1306489 TI - CGRP-immunoreactive primary afferent nerve fibers in the rat urinary bladder: effects of dorsal rhizotomy and MK-801. AB - A transection lesion of the suprasacral spinal cord results in a decreased density of calcitonin gene-related peptide (CGRP)-immunoreactive (I) primary afferent nerve fibers in the rat urinary bladder. The fiber density can be restored by postsurgical treatment with the N-methyl-D-aspartate receptor antagonist MK-801. We are attempting to determine the level of the primary afferent neuron at which MK-801 might have a restorative effect on CGRP immunostaining. Thus, the purpose of this study was to determine if MK-801 had a similar restorative effect on immunostaining for CGRP in bladder nerves after a direct lesion of the sacral afferent system, i.e., rhizotomy of the L6 and S1 dorsal roots. To assess the effect of the lesion, the mean length and number of bladder CGRP-I nerve fibers, as well as the number of CGRP-I perikarya in the L6 and S1 dorsal root ganglia (DRG), were measured following bilateral L6 and S1 dorsal rhizotomies. Both the mean length and the numbers of CGRP-I bladder fibers were significantly decreased by the lesion. However, the number of CGRP-I primary afferent perikarya in the L6 and S1 DRG was unchanged from control values. Rats which received rhizotomies and subsequent treatment with MK-801 did not exhibit restoration of the density of CGRP-I bladder fibers nor an alteration in the number of CGRP-I primary afferent perikarya. These data suggest that MK-801 induced restoration of bladder CGRP-I primary afferent nerve fibers may rely on an intact central process. PMID- 1306491 TI - Changes in glutamic acid decarboxylase mRNA in the pallidum of the rat following unilateral damage of the striatum and overlying cortex. AB - The messenger RNA encoding glutamic acid decarboxylase (GAD) has been examined in the pallidum of the rat using in situ hybridization histochemistry following damage of the striatum and overlying frontal neocortex of one side. Following a postoperative survival time of 5 weeks, ipsilateral shrunken pallidal neurons showed significant decrease in GAD mRNA. The mRNA for GAD is significantly increased in neurons of the contralateral pallidum. These neurons are also significantly enlarged. These findings may be related to pathological changes in pallidal neurons in Huntington's disease. PMID- 1306490 TI - Amyloid precursor protein mRNA encoding the Kunitz protease inhibitor domain is increased by kainic acid-induced seizures in rat hippocampus. AB - A 168-nucleotide exon, found in alternatively spliced amyloid precursor protein (APP) mRNAs, encodes a Kunitz protease inhibitor (KPI) domain. Kainic acid (ip) caused a selective increase of KPI mRNA in rat hippocampus. By in situ hybridization, KPI mRNA was induced in the neuronal layers of the hippocampus 11 12 h after the onset of kainate-induced seizures. The kainate-induced elevation of the KPI-containing APP-770 mRNA was blocked by pretreatment with the anticonvulsant pentobarbital. These data suggest that kainate-induced seizures cause alterations in APP RNA stability and/or processing in rat hippocampal neurons. PMID- 1306492 TI - [Survey and treatment of the blind in Xinhui, Guangdong, China]. AB - Co-operating with Helen Keller International (HKI) in 1987 and 1988, Zhongshan Ophthalmic Center made a large scale prevalent survey of the blind in Xinhui, Guangdong, China. Three screening methods were used in the project. The first was a house-to-house visit by ophthalmologists. The second was performed initially by trained country health workers and then checked by ophthalmologists. In the third one, the blind people were asked to come together to be examined by ophthalmologists. The second method was found to be the most effective. The survey revealed that the prevalent rate of blindness was 0.24% in the county. Of all the blind, 89% were over 50 years old, 73% were females. Cataract accounted for 47% of the blindness. Thirty percent of the blind from cataract received surgical treatment. The postoperative re-examination half a year later showed that the corrected visual acuity in 86% of the patients was more than 0.05. PMID- 1306493 TI - [The experimental studies of the effect of Forskolin on the lowering of intraocular pressure]. AB - The effect of the domestic Forskolin on lowering the intraocular pressure (IOP) of rabbits was studied. The results showed that the Forskolin significantly lowered the normal IOP of rabbits and blocked the ocular hypertension induced by water load in rabbits (p < 0.01). The maximum decrease value of 2%, 1% and 0.5% of the Forskolin was 0.59. 0.36 and 0.19 kPa (1 kPa = 7.5 mmHg), which showed the noticeable dose-effect relationship. Topical ocular application of Forskolin lowered IOP in 1/2 hour, reached to a peak in 2-3 hours and remained significantly for 10 hours. The pupillary diameter did not change when IOP were reduced. Furthermore, the Forskolin had potent stimulative properties to adenylate cyclase (AC). The greater the ability of the Forskolin to stimulate AC, the stronger the effect of IOP lowering. PMID- 1306494 TI - [Glaucomatous hemodynamic changes in central retinal artery and ocular artery]. AB - The hemodynamics of ocular artery (OA) and central retinal artery (CRA) in 100 eyes of 50 normal subjects and 61 eyes of 39 patients with glaucoma were studied with colour doppler image technique. The results showed the hemodynamic characteristics about normal and glaucomatous eyes and that the ischemic change of CRA was one of the high risk factors in glaucomatous visual functional damages. We propose a new classification of glaucomatous hemodynamics and the clinical application of hemodynamic parameters in glaucoma diagnosis. We also, for the first time, make use of hydrodynamic pressure to calculate the retinal perfusion pressure, which explain the phenomena of intraocular pressure increasing with blood flow decreasing and the effect of hyperviscosity as well as cardiovascular disease on glaucoma. A new approach to the research of glaucoma is presented. PMID- 1306495 TI - [The operation treatment for the age-related macular degeneration wet-type eyes and its complications]. AB - Age-related macular degeneration (AMD) is one of the important causes for blindness in elderly population. The effect of the treatments by laser and vitrectomy in AMD wet-type eyes, which subretinal neovascularization is existed in or have vitreous hemorrhage, is reported and discussed. Using laser photocoagulation, 65% of the affected eyes had marked cicatrization and 31% were partially improved. Among the 4 AMD eyes with vitreous hemorrhage, three cases were successful after vitrectomy. It has a certain significance for rescuing the vision and controlling the development in AMD wet-type eyes. PMID- 1306496 TI - [Vitrectomy combined with intravitreal injection of drugs for the management of advanced suppurative endophthalmitis]. AB - Sixty cases (60 eyes) of advanced suppurative endophthalmitis treated by a combination of vitrectomy and intravitreal injection of drugs (antibiotics or/and corticosteroids) were investigated perspectively. Of the 60 cases, 43 were infected after trauma, 12 were infected after surgical procedures, while the others were of unknown causes. During the follow-up period of 1/2-5 years, 57 cases (95%) retained functioning eyes, the postoperative visual acuity of 34 eyes (57%) being 0.05 or better and the postoperative visual acuity of 17 eyes (28%) 0.4 to 1.0. The advantages of the therapeutic regimen are analyzed. We believe that it is the most effective therapy for suppurative endophthalmitis. The timing of the operation and the factors influencing the results are discussed. This report also presents our clinical experiences in the management of advanced suppurative endophthalmitis. PMID- 1306497 TI - [Endogenous uveitis in senior patients]. AB - Forty-seven cases of endogenous uveitis aged 60 and above were analyzed in the retrospective study. The result shows males are more than females (1.2:1). Among the 47 cases, 28 cases (59.57%) are anterior uveitis, 18 cases (38.30%) are panuveitis. Only 1 case (2.13%) is posterior uveitis. Immediated-type uveitis is not found. Besides, 34 cases are non-granulomatosis type, more than the cases with granulomatosis type (13 cases). The major complications are secondary glaucoma (22 cases) and complicated cataract (16 cases). Immunological tests to the patients showed the unbalance of immune-regulation was mostly complicated by immune-related sickness. The cure rate was 40.58%. The invalid and deteriorative rate was 17.39%. 62.32% of the patients had the vision acuity lower than 0.3 after the treatment. PMID- 1306499 TI - [Measuring the threshold of stereopsis for 111 children with amblyopia]. AB - The threshold of stereopsis was measured by static stereopter for 111 children with amblyopia aged from 4 to 13 years. They were divided into three groups: 38 cases ranging in age from 4 to 5 years, 43 cases 6 to 7 and 30 cases 8 to 13. Fifty six cases were unilateral and 55 bilateral amblyopia. The average threshold of stereopsis was 149.64 second angle for the 4-5 group, 66.69 for the 6-7 and 48.48 for the 8-13. The average threshold for unilateral amblyopia was 65.3, in which mild type was 38.6 and under moderate type was 88.84, whereas the average threshold for bilateral cases was 115.81, in which mild type was 44.09 and under moderate type was 175.44. The distribution of stereopsis for different age groups, the threshold of stereopsis influenced by different types of amblyopia and the comparison of amblyopia between bilateral and unilateral are also discussed. PMID- 1306498 TI - [Refractive error and amblyopia in children]. AB - The refractive status of 3,099 children was analyzed. The result showed that the incidence and degree of hyperopia decreased gradually and those of myopia increased along with the growing up of children in ametropia. In binocular refractive amblyopia, high and medium hyperopia and myopia in severe and medium amblyopia were significantly more than those in mild amblyopia. In monocular refractive amblyopia, high and medium hyperopia and high myopia in the amblyopic eyes were more than those in the nonamblyopic eyes. The refractive status of binocular esotropic amblyopia had no significant difference in various ages and degrees of amblyopia. There was also no significant difference between the refractive status of the amblyopic and nonamblyopic eyes in monocular esotropic amblyopia. It was considered that refractive amblyopia was closely related to high ametropia and the deviation of the eye might be the main cause of strabismic amblyopia. PMID- 1306500 TI - [Computerized image analysis for retinal nerve fiber layer: a preliminary report]. AB - The principle and method for analysing the white-black photographs of retinal nerve fiber layer (RNFL) by using the technique of computerized image analysis were introduced. An objective and quantitative result of RNFL on the white-black photograph was initially obtained, and using the technique of fulse colour, each of the RNFL could be showed, which seem to have more advantages than observing RNFL on a white-black photograph. PMID- 1306502 TI - [Hurler syndrome (a case report)]. AB - A case of Hurler syndrome diagnosed by clinical and laboratory examination is reported. The patient's roentgenograms showed the dystrophies of bones, lace shaped ribs, boat-shaped cranium, fishhook-shaped forefront protrusion of silla trucica. Corneal opacities and high ocular pressure were found in both eyes. VEP measurement suggested the defects of optic nerve. The authors emphasized that visual electric physiological examinations should be used to estimate the visual functions when the patient's refractive medium is opqaue. The differential diagnosis was also briefly discussed. PMID- 1306501 TI - [A software design for standard grayscale printout of China-made automatic static quantitative TBC visual field analyser]. AB - A method of "TBC GRAPH" software design for standard grayscale printout of TBC static quantitative perimetry is introduced. The software is operated in IBM PC/XT or PC/AT compatible computer, using Chinese Character Disk Operating System (CCDOS) which has widespread users in China. Symbols were established by using CCDOS word--make function, and sectoral as well as symbolic matrix were made, which realized the standard grayscale printout. The software is recommended for use in ophthalmic clinic and education. PMID- 1306503 TI - The role of calcium in DNA synthesis and development of mouse preimplantation embryos in vitro. AB - The effect of calcium upon embryonic growth was studied using cultured mouse preimplantation embryos. Both morphological development of the embryos and embryo DNA synthesis were shown to be dependent on the Ca2+ concentration in the medium in which the embryos were grown. Reduction of the calcium concentration below 10( 5) M completely blocked cell division and blastocyst formation in the cultured embryos, but only moderately inhibited embryo DNA synthesis. Trifluoperazine, a calmodulin antagonist, strongly inhibited the Ca(2+)-dependent DNA synthesis in the embryos. On the other hand, the drug only slightly affected the morphological development of the embryos. These results demonstrate that calcium independently affects two different aspects of the embryo development, i.e. DNA synthesis and cell division. It is suggested that the former effect is calmodulin-dependent, while the latter involves the calcium-dependence of metabolite transport through the cell membranes. PMID- 1306504 TI - Toxicity of Fastac 10 EC, a pyrethroid insecticide, to Paramecium primaurelia and Tubifex sp. AB - The pyrethroide, Fastac 10 EC was tested on the paramecia and Tubifex sp. The results showed that both tests are valid for estimation of the toxicity of the pesticide. However, the Paramecium test is more sensitive when one is investigating the direct toxicity of the compound. The great validity of the Tubifex test lies in the possibility of tracing the teratogenic effects of the pesticides. PMID- 1306505 TI - Species of the Paramecium aurelia complex in the middle Sudeten of Czecho Slovakia. AB - On the investigated territory three species of the complex were identified, namely Paramecium biaurelia, P. triaurelia, and P. novaurelia. P. novaurelia dominated over the other species with regard to the number of clones established from nature as well as to habitats. PMID- 1306506 TI - Effect of the immature cytoplasm on the duration of the interautogamous interval (IAI) in Paramecium tetraurelia. AB - Cytoplasm in the quantity of about 5% of the cell volume was transferred from young clonal age donors into older recipients. The experimental post transplantation clones showed statistically significant prolongation of the IAIs as compared with those stemming from the original recipients or donors. This suggests that the cytoplasm of young postautogamous cells contains a component retarding the expression of the autogamy-inducing gene(s). PMID- 1306507 TI - Cell proliferation in the germinal layer of the lateral brain ventricles in normal adult mice and under some experimental conditions. AB - Histological and autoradiographic studies revealed mitotic activity in the subependymal germinal layer in the brains of adult mice. The number of mitoses observed was higher in animals subjected to administration of haematoporphyrin and selenourea. PMID- 1306508 TI - Circadian rhythm in the pineal organ of the yellow-bellied toad, Bombina variegata (L.), under laboratory conditions. AB - A circadian morphological rhythm of the pineal organ, as judged by changes in the nuclear volume of the photoreceptor cells, was found in sexually mature male Yellow-bellied toads (Bombina variegata) maintained continuously at 26 degrees C and on a 17L/7D illumination cycle. The greatest nuclear volume occurred at the photophase (16.00 h), and the lowest at the end of the scotophase (4.00 h). PMID- 1306509 TI - Studies on the biology of Argas (A.) reflexus (Fabricius, 1794) (Acari: Ixodida: Argasidae). 2. Effect of alternating temperatures on embryonic development and egg hatch. AB - The paper presents the results of observations on the effect of temperature alterations between 9 degrees C and 30 degrees C every 6 and 12 hours, respectively, on the embryonic development and egg hatch of Argas (A.) reflexus. No effect of the frequency of temperature changes on the percentage of egg mortality, embryo mortality, abnormal egg hatching, or egg hatching into morphologically normal larvae was observed. The experiments showed that in changes temperature have a particularly detrimental effect on the eggs prior to blastulation. PMID- 1306510 TI - Assessment of insulin resistance in vivo: application to the study of type 2 diabetes. AB - Besides insulin secretion, insulin sensitivity plays a key role in the feedback glucose-insulin closed loop. It can be altered in numerous physiological, pathological and pharmacological conditions. It can be estimated in vivo using methods that open the feedback loop (insulin suppression test, glucose clamp) or that analyze the closed loop by employing mathematical models of glucose kinetics. The most popular method is the euglycemic hyperinsulinemic glucose clamp. This test should be ideally coupled with a priming-constant infusion of a glucose tracer together with indirect calorimetry. This combination allows to study the glucose kinetics (Ra and Rd, and thus endogenous-mainly hepatic-glucose production) and its metabolism (oxidation or storage as glycogen), respectively. One alternative approach is the frequently sampled intravenous glucose tolerance test where the dynamic changes in plasma insulin and glucose levels are analyzed using the so-called 'minimal model' method. Noninsulin-dependent or type 2 diabetes is characterized by a significant defect in both insulin secretion and action. The insulin resistance is located at the liver site (increased glucose production) and at the peripheral tissues (decreased oxidation and, even more, defective storage of glucose in the muscles). This insulin resistance, which predominates at the postreceptor level, seems to be genetically determined but is worsened by weight excess and by hyperglycemia itself. This contributes to a vicious circle which aggravates progressively the severity of the disease. PMID- 1306511 TI - The syndrome of insulin resistance. AB - It is well known that excessive weight is associated with resistance to insulin mediated glucose uptake and predisposition to the development of type II diabetes. It has been shown more recently that excessive weight and insulin resistance tend to be associated to android fat distribution, arterial hypertension, elevated levels of triglycerides, low concentration of HDL cholesterol and defective fibrinolysis. The terms syndrome of insulin resistance, metabolic syndrome or syndrome X have been proposed to describe this cluster of abnormalities. The pathophysiological mechanisms which could explain the interrelations between these different parameters are still only partly understood. Epidemiological prospective studies have demonstrated that the metabolic syndrome is a risk factor for coronary heart disease and type II diabetes. The mechanisms involved in the development of diabetes are relatively well established, but those which are implicated in the atherothrombotic process are far from being clearly described. Anyway, sufficient presumption exists to attempt at decreasing insulin resistance when it exists. Physical training and, if indicated, weight reduction are the simplest means. PMID- 1306512 TI - Hyperinsulinemia, insulin resistance and essential hypertension. AB - Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients. PMID- 1306513 TI - Hypertriglyceridemia: cause or consequence of insulin resistance? AB - An overproduction of VLDL by the liver and a slower clearance of these lipoproteins are usually seen in diabetic patients. There is correlation between insulin resistance and plasma triglyceride concentration. Triglyceride may influence an early step in the insulin action pathway and alternatively, insulin resistance may cause hypertriglyceridemia. Hyperinsulinemia and/or hypertriglyceridemia may play a strong role in the cardiovascular risk of patients with type II diabetes. There is an important need to conduct trials to define therapy that can reduce the risk of cardiovascular complications. PMID- 1306514 TI - Insulin resistance and polycystic ovarian syndrome. AB - Insulin resistance (IR) and polycystic ovarian syndrome (PCOS) appear as linked phenomena, although this is not easy to obviate in common forms of PCOS while it is evident in the rare cases of extreme IR and hyperinsulinism (HI). Experimental data indicate that insulin could interfere with the local insulin-like growth factor systems in ovaries, and presumably in adrenals and in the hypothalamic pituitary system. The female puberty system offers a physiological model to explain the gonadotropic action of insulin. In patients with IR, HI could induce a state of hyperpuberty, leading to the constitution of PCOS during adolescence. PMID- 1306515 TI - Age-related insulin resistance: a review. AB - Impaired glucose tolerance occurs with age. This impairment is multifactorial including a decrease in insulin-mediated glucose uptake by peripheral tissues and a delay in insulin-induced suppression of hepatic glucose output. A post-binding defect in insulin action such as a reduced capacity to transcribe more glucose transporter mRNA and/or a reduced translocation of preformed glucose transporters to plasma membrane is incriminated. However, insulin resistance with age is not a constant finding and other mechanism(s) has (have) to be involved in old individuals with impaired glucose tolerance and normal tissue insulin sensitivity. PMID- 1306516 TI - Molecular basis of insulin resistance. AB - The recent application of recombinant DNA technology to clinical investigation now allows the identification of the molecular alterations responsible for insulin resistance. In this review, the recent knowledge concerning these investigations is reported. Genetic mutations of the insulin gene as the source of insulin resistance have been reported for a long time. More recently a series of mutations of the insulin receptor gene have been identified as the cause of the extreme insulin resistance, observed in rare syndromes, such as type A insulin resistance or leprechaunism. However, it is probable that the majority of the molecular defects causing insulin resistance occur at the postreceptor level. The key proteins involved in the different intracellular signalling pathways of insulin are only partly identified. A better understanding of the mechanisms of insulin action is essential for the identification of corresponding genetic alterations. The investigations concerning the glucose transporter GLUT4 and glucokinase genes are good examples of complex but promising research, which has recently started. Elucidation of the genetic and molecular basis of diseases such as type II diabetes or other states associated with insulin resistance, is the long-term goal. PMID- 1306517 TI - Pharmacological approach in the treatment of insulin resistance. AB - Insulin resistance syndromes are heterogeneous in either severity or mechanism. Many drugs have been shown to counteract various elements of insulin resistance. Some of them, by normalization of metabolic parameters, decrease insulin resistance induced by chronic hyperglycemia in diabetes. Insulin and, to some extent, sulfonylureas are in this group, but these drugs are not stricto sensu medication of insulin resistance. Some drugs sensitize peripheral tissues to the action of insulin. For instance, biguanides and thiazolidine-dione facilitate translocation to the membrane of glucose transporter in presence of insulin. Other compounds as vanadate or IGF-1 mimic some peripheral action of insulin. Finally, blockade of FFA oxidation by specific inhibitors (methylpalmoxyrate) can limit insulin resistance. In 1992, among these compounds, specific of insulin resistance, biguanides are mostly used. However, the efficacy of these drugs is moderate and limited to type 2 diabetes. PMID- 1306518 TI - The thyroid hormone receptors: molecular basis of thyroid hormone resistance. AB - Major progress has been achieved in the mechanism of action of thyroid hormones thanks to the identification of the T3 receptor as the product of the proto oncogene c-erbA. Recognition of subsets of receptors with and without T3-binding properties and of the interaction of different receptors with each other leads to new insights in cell regulation and development. In thyroid hormone resistance, distinct mutations in the T3-binding domain of thyroid hormone receptor (TR)beta have been identified in unrelated families. No correlation between the type of mutation and tissue resistance has been established. Mutant TRs bind to thyroid hormone response elements (TREs) on both negative or positive T3-controlled genes. Subjects with heterozygous TR beta gene deletion are not affected, supporting the hypothesis that mutant TRs act through a dominant negative effect. In generalized thyroid hormone resistance, mutated TR beta may interfere through competition for TREs and/or formation of inactive dimers. Finally, deficiency in T3 receptor auxiliary protein or other accessory proteins or competition between mutant and normal TRs for these factors is not excluded. PMID- 1306519 TI - Thyroid hormone generalized resistance. AB - The syndromes of thyroid hormone resistance may affect overall or only some tissues. The generalized resistance is an inherited disease which involves a familial eumetabolic or hypometabolic goiter, increased free thyroid hormones with normal or elevated plasma TSH levels; children may present mental retardation, deafness, short stature and delayed bone age. The disease is frequently misdiagnosed. In vivo and in vitro tests may be used to assess the diagnosis. The defect of increment of sex hormone-binding globulin after administration of T3 may be useful in the demonstration of the disease. Therapy uses high T4 or T3 doses in hypometabolic patients. The generalized thyroid hormone resistance could be linked to abnormalities at the T3 receptor and c-erb A gene level, as a consequence of different point mutations or deletions involving the hormone-binding domain. PMID- 1306520 TI - Pituitary resistance to thyroid hormones. AB - Pituitary thyroid hormone resistance (PRTH) refers to a particular form of thyroid hormone refractoriness that is accompanied by peripheral hyperthyroidism, as only the TSH-secreting pituitary cells appear to be resistant to the effects of thyroid hormones. The presence of PRTH is suspected and diagnosed on the basis of the finding of high free thyroid hormone levels along with unsuppressed TSH, clinical signs and symptoms of hyperthyroidism and values of at least one of the parameters evaluating peripheral thyroid hormone action in the hyperthyroid range. However, most patients with PRTH present with clinical signs and symptoms of thyroid dysfunction, particularly goiter and tachycardia, overlapping those recorded in patients with generalized thyroid hormone resistance (GRTH), i.e. refractoriness to thyroid hormones at both pituitary and peripheral tissue level. Moreover, most of them display normal values of other parameters evaluating the peripheral effects of thyroid hormones and bear mutations in the gene encoding for T3 nuclear receptors similar to those found in patients with GRTH. These findings are questioning the existence of PRTH as a separate clinical entity and support the view that the various forms of thyroid hormone resistance may be part of a spectrum of disease with variable expression in different issues. PMID- 1306521 TI - Differential initiation of translation of a single estrogen receptor mRNA could explain some estradiol resistance cases. AB - Cell response to steroid stimulation is generally acknowledged to be mediated by an intracellular protein known as a receptor. Response intensity is related to the affinity of the receptor and to the number of sites occupied by its specific ligand. Although verified in the majority of experimental and clinical studies, certain phenomena of steroid hormone resistance would seem to challenge this assertion. Application of gene molecular biology to determine the action mechanisms of steroid hormones has partially explained cell resistance in terms of genetic modifications. The work presented here shows that in certain cases, estrogen resistance could be explained by regulation of translation of the single messenger RNA coding for the receptor. PMID- 1306522 TI - D2 dopaminergic receptors: normal and abnormal transduction mechanisms. AB - Dopamine receptors of D2 type present on lactotroph cells are coupled to a large series of transduction mechanisms. Beside their negative coupling with adenylate cyclase, they are also coupled with potassium and calcium channels, leading to a decreased intracellular calcium concentration. In addition, D2 dopamine receptors also modulate phospholipase activities. Dopamine inhibits inositol phosphate production, through two distinct mechanisms. One of them could represent a direct negative coupling with phospholipase C. All these transduction mechanisms of the D2 dopamine receptors implicate G proteins sensitive to pertussis toxin. In contrast, these receptors are negatively coupled to phospholipase A2 through G proteins insensitive to this toxin. Both isoforms of the D2 dopamine receptor, generated by alternate splicing of a single gene, are present in lactotroph cells. After transfection in CH4C1 cells the two isoforms are coupled with adenylate cyclase while only the shortest isoform appears negatively coupled to phospholipase C. Functional D2 dopamine receptors are present in human prolactinomas. Resistance to bromocriptine therapy is associated with a decreased density of these receptors in the tumor. In addition, the ratio of the two receptor isoforms (measured by PCR) is different in responsive and resistant tumors. Furthermore, the activity of Gi/Go proteins coupled to adenylate cyclase appears also affected in resistant tumors. Resistance to bromocriptine therapy appears thus to involve multiple changes at the different levels of the multiple mechanisms of action of dopamine on lactotroph cells. PMID- 1306523 TI - Prolactinomas and resistance to dopamine agonists. AB - Among 288 patients with prolactinoma (aged 12-62 years; 242 women), 27 were diagnosed as resistant to bromocriptine as their plasma prolactin (PRL) levels remained elevated despite long-term (3 months or more) treatment at high doses (> or = 15 mg daily). These 18 women and 9 men, aged 29 +/- 9 years (mean +/- SD, range 13-50), followed-up for 8 +/- 4 years, had microadenomas (n = 6) or macroadenomas. They were treated by dopamine agonists alone (n = 6) or associated with surgical or radiation therapy. In 8 cases repetitive surgical treatments were necessary. Among the 24 patients who were treated with the nonergot dopamine agonist CV 205-502 after unsuccessful bromocriptine treatment, half of them (9 women, 3 men) resumed normal PRL levels on doses ranging from 0.15 to 0.45 mg/day. Despite daily doses of CV 205-502 from 0.3 to 0.525 mg, the remaining patients were not normalized by this drug which did not prevent tumor growth in 4 of them. Two patients died from invasive cerebral extensions of their tumor and a third had vertebral metastases with positive anti-PRL immunostaining. It is concluded that bromocriptine-resistant prolactinomas represent the most severe aspect of this disease and that a more powerful dopamine agonist like CV 205-502 is effective in only a fraction of these patients. PMID- 1306524 TI - G-protein oncogenes in acromegaly. AB - G-proteins belong to a family of proteins which share the common properties of GTP binding and hydrolysis. Heterotrimeric G-proteins are composed of alpha-, beta- and gamma-subunits. The alpha-subunit which differs from one G-protein to another contains the GDP/GTP binding site and has intrinsic GTPase activity. The receptor occupancy causes displacement of bound GDP by GTP, dissociation of free beta gamma-dimer and alpha-GTP complex, interaction of the activated alpha-GTP complex with intracellular effectors, such as enzymes and ion channels. The turn off of the reaction is due to the GTPase activity which causes the hydrolysis of GTP to GDP. G-proteins are essential for transferring hormonal signals from cell surface receptors to intracellular effectors. Since G-proteins generate intracellular effectors involved in cell growth, G-protein genes have the propensity to be converted into oncogenes. In fact, mutations in the alpha subunit of Gs (the G-protein involved in the activation of adenylyl cyclase) have been demonstrated in 40% of human GH secreting pituitary adenomas. Single amino acid substitutions replacing Arg 201 with either Cys or His or Gln 227 with either Arg or Leu cause constitutive activation of adenylyl cyclase by inhibiting GTPase (gsp oncogene). The same mutations were identified in about 10% of thyroid adenomas and in the McCune-Albright syndrome. PMID- 1306525 TI - Resistance to somatostatin (SRIH) analog therapy in acromegaly. Re-evaluation of the correlation between the SRIH receptor status of the pituitary tumor and the in vivo inhibition of GH secretion in response to SRIH analog. AB - The development of a long-acting somatostatin (SRIH) analog (octreotide, Sandoz) has been a major breakthrough in the treatment of acromegaly. However, in 20-30% of the patients, growth hormone (GH) plasma levels remain elevated (> 10 micrograms/l) despite treatment with octreotide. This raised the concept of resistance to SRIH analog therapy in acromegaly. Indeed, in vivo response to SRIH analogs varies greatly among acromegalic patients. According to the reviews in the literature and our own autoradiographic data, no direct correlation can be established between the GH response to octreotide and the number or affinity of the SRIH receptors located on the tumor. In our series a greater density of SRIH receptors is present on tumors from patients very sensitive to the SRIH agonist. A subset of patients resistant to octreotide could result from a very low density of SRIH receptor although this type of GH-secreting tumor constitutes certainly a rare case. A subset of GH-secreting pituitary tumors can be characterized by a mutation on the alpha subunit of the guanine nucleotide-dependent protein coupled to the stimulation of adenylate cyclase (G alpha s). This mutation results in a high basal adenylate cyclase activity and a low GHRH-stimulated activity. However, when the adenomas are separated according to their basal adenylate cyclase activity, SRIH is able to decrease cAMP levels in both types of tumor. In addition, in our series no direct correlation is observed between the SRIH inhibition of adenylate cyclase and the amount of SRIH-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306526 TI - External fixation using simple pin fixators. PMID- 1306527 TI - Effects of high and low dietary fat and indomethacin on tumour growth, hormone receptor status and growth factor expression in DMBA-induced rat breast cancer. AB - The effects of high and low dietary fat (20% vs. 0.5% corn oil), and of the prostaglandin synthetase inhibitor indomethacin (0.005% w/w), on tumour incidence, tumour growth, hormone-receptor status and growth-factor expression were examined in dimethylbenzanthracene (DMBA)-induced rat breast cancer. The high dietary-fat group showed a significantly higher tumour incidence, larger tumour size and larger number of bromodeoxyuridine(BrdU)-positive cells of tumours as compared with those in the low dietary-fat group. Indomethacin reduced tumour incidence significantly, but conversely increased the tumour size and the number of BrdU-positive cells in both the high and the low dietary-fat groups. No significant difference was noted in the hormone-receptor status of the tumours. Growth factors (TGF-alpha and IGF-II) were somewhat highly expressed in the high dietary-fat group as compared with the low dietary-fat group, but indomethacin rather reduced the growth-factor expression. It is concluded that high dietary fat stimulates tumour incidence and tumour proliferation, while indomethacin has dual effects: a stimulating effect on tumour proliferation, but an inhibiting effect on tumour incidence. It is also suggested that hormone-receptor status and growth-factor expression do not play an important role in their stimulating effects on tumour proliferation. PMID- 1306528 TI - Indomethacin-induced intestinal ulcers are associated with an increased number of peripheral T lymphocytes in the rat. AB - Indomethacin (8 mg/kg per os) induced small-intestinal ulcers which were associated with an increased percentage of total number and T-helper peripheral lymphocytes. An increase in intestinal flora and a decrease in mucosal permeability due to indomethacin treatment are among the factors which favour the cytotoxic T-cell reactions and the resulting increase in lymphocytes. PMID- 1306529 TI - Effect of ethanol chronic use on hepatotoxicity in rats exposed to tetrachloroethylene. AB - Tetrachloroethylene, an industrial halogenated solvent, shows several toxic effects. Also at hepatic level this substance can induce a damage but this effect is present only after high exposure, but such high levels have not been found in work environments. Using Wistar rats, we wanted to check whether the chronic administration of ethyl alcohol can modify the action of tetrachloroethylene. Tetrachloroethylene was administered by aerosol and alcohol at the concentration of 15% in drinking water. We observed an increase in plasma triglycerides, and evident histological alteration as a result of steatosis, in rats drinking alcohol as compared to a control group; the administration of tetrachloroethylene to rat drinkers of alcohol did not cause an increase in plasma triglycerides and steatosis as compared to rat drinkers of alcohol, but on the contrary we observed a decrease in alcohol-induced liver damage. PMID- 1306530 TI - Activation of bladder mast cells in interstitial cystitis. AB - Interstitial cystitis (IC) is a sterile, inflammatory bladder condition characterized by urinary frequency and urgency, as well as burning and suprapubic pain, which occurs more frequently in women who may suffer for years before diagnosis. An increased number of mast cells have been associated with IC, but the published reports are inconclusive and often conflicting. Human bladder biopsies were analysed blindly for the degree of activation of mast cells in control and IC patients. It was found that mast cells from IC patients averaged as high as 34 cells/mm2 as compared to less than 16/mm2 in controls. Electron microscopy revealed that over 90% of mast cells from IC patients were activated to various degrees. It is concluded that mast cell activation is a pathologic characteristic for IC. PMID- 1306531 TI - Contempo 1992. PMID- 1306532 TI - [Activity of selected enzymes of the anti-oxidase system in the vitreous body, aqueous humor and lens after subconjunctival ozone in experiments]. AB - The influence of ozone on the activity of enzymes of the antioxydation system in selected structures of the eye were checked. Ozone given topically in weak concentrations acts stimulating, increasing the activity of the enzymes of the antioxydation system, instead in high concentrations causes a significant reduction of activity of the enzymes of the mentioned system. PMID- 1306533 TI - [Value of gentamycin concentration in aqueous humor of a rabbit's eye depending on the method of application. Summary of a doctoral thesis]. AB - Pharmacokinetics of gentamycin in the primary and secondary rabbit's aqueous was examined by using a new experimental method of subconjunctival application (without breaking the continuity of the conjunctiva). It was established that after subconjunctival application one cannot obtain any therapeutical concentrations in the primary or secondary aqueous. Presented are conditions which have to be fulfilled to obtain a therapeutical concentration of gentamycin in the secondary aqueous. PMID- 1306535 TI - [Retinal changes accompanying acute pancreatitis]. AB - Observed were 12 patients with acute pancreatitis claiming to suffer various kinds of visual disturbances. All the examined patients exhibited changes in the eye fundus localized mainly in the area of the posterior pole. As the general condition was improving the fundus changes slowly receded. PMID- 1306534 TI - [Evaluation of the macula which was not involved in retinal detachment after surgical treatment of retinal detachment using scleral indentation. Summary of a doctoral thesis]. AB - The goal of the study was the evaluation of the influence of the nowadays most frequently used surgical methods in cases of retinal detachment on the macula not involved in the detachment. The study takes into account surgical interventions which have the same indications and principles of action. They are based on an extra-scleral indentation--temporary or permanent one--by means of a Lincoff Kreissig balloon and a meridional silicone sponge implant. The examinations comprised 54 patients. They were divided into 2 groups: 1st group (24 patients) was treated by cryopexy and a Lincoff-Kreissig balloon, the 2nd group (30 patients) by cryopexy and a meridional silicone sponge implant. In all the patients of both groups the retina reattached. During the 5-years observation of patients of the 1st group no macular changes were detected; one did not observe metamorphopsia or disturbances of the color vision. In the 2nd group instead 17 patients claimed metamorphopsia, 20 patients showed disturbances of the color vision and angiography changes involving the macular region (13 patients). PMID- 1306536 TI - [Various clonidine drops in treatment of glaucoma]. AB - Seventeen patients with glaucoma were given bilaterally a single drop of Isoglaucon (Clonidine hydrochloride) of various volume (15 microliters and 40 microliters) and various concentrations of the drug (0.125%, 0.25%, 0.50%) according to the principle of a double blind trial. In comparison with placebo all sorts of Isoglaucon drops cause a statistically important reduction of intraocular pressure; an essential lowering of the general systolic and diastolic pressure (a side effect of the treatment) appeared after application of a larger drop (40 microliters) of a 0.5% concentration. By reducing the content of the drug in the drop or reducing its volume one can avoid the fall in the general blood pressure. PMID- 1306537 TI - [Naclof and dexamethasone in topical application after trabeculectomy]. AB - Evaluated was the topically applied solution of natrium salt of diclofenac- Naclof (22 eyes) and a 0.1% solution of dexamethasone phosphate (23 eyes) on the healing of postoperative wounds after trabeculectomy in a clinical examination in patients with simple glaucoma. After the filtering operation the authors observed in the group of patients treated by dexamethasone a longer and more pronounced flattening of the anterior chamber (up to 14 days) a greater hypotensive effect and a more increased facility of the outflow (in an observation period of 6 months). In the case of a considerable flattening of the anterior chamber after trabeculectomy application of Naclof gives a better prognosis than of dexamethasone. PMID- 1306538 TI - [Surgical treatment of low pressure glaucoma]. AB - Eyes with non-controlled--in spite of a conservative treatment--bilateral low tension glaucoma with a decreased facility of outflow (10 patients, 20 eyes) were subjected to antiglaucoma operations. Trabeculectomy was performed in one eye, a filtering operation in the second one. During the observation period of 1.5 years it showed that in the low-tension glaucoma the visual function undergoes more frequently stabilization after a more radical glaucomatous procedure (of filtration type) when the postoperative fall in the intraocular pressure exceeds 20% and its daily oscillations are considerably reduced. PMID- 1306539 TI - [Inter-capsular technique of cataract extraction with implantation of intraocular disc lenses--own material]. AB - The authors present personal results and complications of surgery with application of intraocular disc lenses. Evaluation of this model of intraocular lenses is positive. The authors are encouraging to their use. PMID- 1306540 TI - [Significance of anterior and posterior lens capsule in inter-capsular cataract surgery]. AB - Anterior as well as posterior lens capsule are nowadays the object of interest because of their importance. Discussing the cataract surgery the author presents the role of the lens capsule in the process of the inter-capsular technique of cataract extraction and in the postoperative course. PMID- 1306541 TI - [Methods of preventing opacification in the posterior lens capsule after extracapsular cataract extraction]. AB - The methods of extracapsular cataract extraction generated some problems connected with postoperative opacification of the posterior capsule. The authors present clinical and experimental methods applied nowadays, intended to prevent these opacifications from forming. PMID- 1306542 TI - [Late results of stomatologic and ophthalmologic treatment of injuries involving the central part of the face]. AB - The authors present an analysis of the results of treatment of patients with injury of the central fragment of the face, who have been hospitalized in the 2nd Department of the Maxillofacial surgery in Silesian Academy of Medicine. In the period 1980-1987 there were 447 patients with an injury of the central fragment of the face. Among this group 60 (13.4 p.c.) patients showed disturbances of the visual system. The most frequent causes of the injury were: assault (61.5 p.c.), traffic accidents (20.1 p.c.), occupational injuries (8.8 p.c.). Deformation of the face was the most frequent pathology observed in the course of a control stomatological check-up (32.0 p.c.). The most important ocular pathology were the posttraumatic atrophy of the eye (3.3 p.c.) and optic atrophy. Palpebral scars (33 p.c.) and diplopia (7.6 p.c.) were the most frequent ocular signs. PMID- 1306543 TI - [Principle and technique of magnetic resonance tomography in ophthalmology]. AB - The phenomenon of the magnetic resonance and methods of its representation are described. A standard technique of spin echo used in ophthalmology is presented. PMID- 1306544 TI - [Indications for magnetic resonance tomography in examination of the orbit]. PMID- 1306545 TI - [Ocular manifestations in AIDS]. PMID- 1306546 TI - Cardiovascular risk factors, clustering and complications in overweight young men. PMID- 1306547 TI - Understanding and underwriting sleep apnea. PMID- 1306548 TI - The expanding role of the insurance medical director--carving out a bigger niche. PMID- 1306549 TI - The technology revolution--from the past to the future: implications for insurance medicine. PMID- 1306550 TI - Advances in cardiac surgery 1992; impact on disability and mortality. PMID- 1306551 TI - Mortality following various surgical procedures in the 34,000,000 Medicare population. PMID- 1306552 TI - Job-related stress as a cause of disability--a disease of the 90s or a means for early retirement? PMID- 1306553 TI - Hypertension in the elderly: are there benefits to treatment? PMID- 1306554 TI - Rheumatology: aches, pains and alphabet soup--new developments and understanding diagnostic tests. PMID- 1306556 TI - Genetic testing committee report. PMID- 1306555 TI - AIDS committee report. PMID- 1306557 TI - Tumor marker committee report. PMID- 1306558 TI - ACLI public affairs report. PMID- 1306559 TI - ACLI Legislative/regulatory report. PMID- 1306560 TI - Life and health medical research fund presentation. PMID- 1306561 TI - Medical Information Bureau update. PMID- 1306562 TI - Geriatrics: what you don't know can hurt you. PMID- 1306563 TI - Cytokines and monoclonal antibodies: an introduction of their current and future applications to cancer and other diseases. PMID- 1306564 TI - Values and hard choices: challenges for life insurance medical directors. PMID- 1306565 TI - Coronary artery disease in women--are women different at heart? PMID- 1306566 TI - [Assessment of clinical course of myocardial infarction complicated by atrioventricular conduction disorders]. AB - The aim of the study was to assess the clinical course of myocardial infarction complicated by atrioventricular conduction disorders. The patient group consisted of 155 subjects, 117 men and 38 women, aged 31-91 (mean = 61 years). Analysis included the type and frequency of AV conduction disorders with respect to the infarct site and size, the presence of complications, therapy used with particular consideration of temporary electrical stimulation. AV conduction disorders were found in 15.8% of patients with myocardial infarction. They were found significantly more frequently in those with the inferior myocardial infarction. The patients with the infarction complicated by AV conduction disorders showed more extensive myocardial necrosis, with the degree of the block correlating with the infarct size, more frequent occurrence of such complications as cardiogenic shock, pulmonary edema. Despite the use of electrical stimulation the mortality rate in the myocardial infarction complicated by complete AV block was high, reaching 50.7%. PMID- 1306567 TI - [Estimation of renal tubular function after uropoline administration in certain disease states]. AB - 24 h urinary excretion of beta-microglobulin (beta 2M) and Tamm-Horsfall protein (THP) before and after administration 40 ml of 75% Uropoline were assessed, as a specific markers of proximal and distal tubular dysfunction respectively. 22 patients without renal diseases and hypertension (C), 22 hypertensive patients (HP), 14 patients with renal stone disease (RSD) and 16 patients with pyelonephritis (PN) were examined. Administration of Uropoline did not change beta 2M and THP urinary excretion in C, but increased beta 2M excretion in HP and decreased THP urinary excretion in patients with RSD. It is concluded, that Uropoline shows a noxious effect on the proximal tubule in HP and on the distal tubule in patients with RSD. PMID- 1306568 TI - [Examination of cortisol and insulin levels in serum of patients with primary hyperlipoproteinemia and phenotype IIa and IIb during lovastatin treatment]. AB - Serum cortisol and insulin concentrations were determined in 30 patients with primary hyperlipoproteinemia (HLP) phenotype IIa (20 persons) and IIb (10 persons) during treatment with lovastatin. Lovastatin dosage varied from 20-80 mg daily. Serum insulin concentration did not change significantly after lovastatin treatment. Serum cortisol concentration significantly increased after 12 weeks of treatment. Cortisol concentration changes were different in HLP IIa and IIb patients. In HLP IIa cortisol concentration increased from 21.9 micrograms/dl to 28.1 micrograms/dl after 12 weeks of treatment, in HLP IIb cortisol level decreased from 31.3 to 24.1 micrograms/dl after 4 weeks of treatment and increased to 32.3 micrograms/dl after 12 weeks of therapy. Mean cortisol concentration was significantly higher in HLP IIa than HLP IIb patients. LDL cholesterol concentrations changes after treatment correlated significantly with baseline cortisol concentration in HLP IIa group (r = -.34), changes in HDL cholesterol concentration with baseline insulin levels in HLP IIb patients (r = .54). PMID- 1306569 TI - ["White coat hypertension" syndrome in resistant essential hypertension]. AB - The study population included 51 patients, aged 34-67 years with essential arterial hypertension treated with 3-5 hypotensive drugs at the Outpatient Antihypertensive Department. Based upon frequent measurements of elevated arterial blood pressure values they were found to be therapy resistant. 24-h ambulatory blood pressure monitoring recorded at one hour intervals (Space Labs) excluded 8 patients (15.7%) from the resistant hypertension group as the number of values > 140/90 mm Hg did not exceed 25% of the measurements. In these patients white coat hypertension was the reason for diagnosing resistance. In 18 patients (35.3%) the initial diagnosis was confirmed as the number of increased values was 80-100%. The severity of eye fundus changes, higher blood pressure values and male predominance characterized the resistant group. The use of long term noninvasive automatic blood pressure recording helps us to exclude pseudo resistance and avoid further intensification of treatment. PMID- 1306570 TI - [Levels of beta-endorphin in serum of patients with chronic renal failure on conservative treatment during insulin-induced hypoglycemia stimulation testing]. AB - beta-endorphin (BE) and other opioid peptides participate significantly in the development of the uremic syndrome. In patients with chronic renal failure (CRF) an elevated serum BE level and lack of a twenty-four-hour BE-secretory pattern were found. In 14 patients with CRF on conservative treatment with serum creatinine above 500 mumol/l and in 14 healthy subjects serum BE was evaluated after intravenous insulin injection. An adequate hypoglycemia was obtained in every subject. Basel serum BE concentration was significantly higher in patients with CRF than in healthy subjects and correlation positively with creatinine. After 60 min. from insulin injection in both groups the peak BE level was observed here after 120 min. it returned to the initial values. The curve of BE concentration in patients with CRF ran significantly higher than in healthy subjects. A total secretory answer of the pituitary measured by the area over basel value of BE was similar in both groups. It seems that BE secretion by the corticotropic cells of the pituitary is unchanged in patients with CRF. Impaired BE elimination by the kidneys is probably responsible for hyper-beta-endorphin levels in those patients. PMID- 1306571 TI - [Ribonuclease in clinical studies]. PMID- 1306572 TI - [Phosphatidylinositols as a source of second messengers of information]. PMID- 1306573 TI - [Effective treatment of Burkitt's lymphoma with spinal cord compression in a 15 year old boy]. PMID- 1306574 TI - [Malignant neurilemmoma of the abdomen (neurilemmoma malignum, schwannoma malignum). Case report]. PMID- 1306575 TI - [Report on activities of the Regional AIDS Outpatient Clinic of Infectious Diseases Hospital Medical Academy in Cracow]. PMID- 1306576 TI - [Experimental study of external fixation of femoral fractures. Mechanical properties of different kinds of fixation. Clinical implications]. AB - An in vitro assessment of the mechanical performance of 10 types of external femoral stabilization allowed the amplitudes of fracture site displacements during the initial loading phase of a comminuted fracture treated by external fixation to be established. The largest displacement to load ratios were observed in the sagittal plane for all tested configurations. The highest fixator stiffnesses were obtained by using large diameter tubes and pins. The most rigid fixators have a derigidification system which creates the problem of choosing the ideal time to change the rigidity. PMID- 1306577 TI - [Femoral and tibial bone torsions associated with internal femoro-tibial osteoarthritis. Index of cumulative torsions]. AB - Among the hypothesis about pathogenesis of medial knee osteoarthritis, the participation of modifications of the alignment of the limb in the frontal plane is known. The participation of the femoral and tibial torsions had been assessed by a few authors. In this study, the torsions have been measured by computerized tomodensitometry. The global torsional morphology of the limb has been defined by the measure of the Index of Cumulated Torsions. The values of torsions have been compared with the angle deformities measured in the frontal plane. The effects of the bone torsions on the position of the lower limb during the weight-bearing phase of the gait and the consequences about the knee have been studied. PMID- 1306578 TI - [Total knee replacement after valgus tibial osteotomy. Technical problems]. AB - Forty total knee replacements following valgus tibial osteotomy were analysed. There were 38 patients (10 men and 28 women) with a mean age of 72 years at the time of the joint replacement, at a mean of 8.5 years after osteotomy. Mean follow-up was 3 years (1 to 5 years). Performing a total knee replacement after valgus tibial osteotomy posed some specific problems due to asymmetrical bone cuts, residual ligament laxity, loss of bone at the tibial plateau, and especially when there was a malunion of the previous osteotomy. The functional results were good. A group of 208 patients with total knee replacements for untreated osteoarthritis acted as a control for comparison. In the group with an osteotomy the results were worse in respect of the walking distance and flexion angle achieved after joint replacement compared with primary replacement (p < 0.001). However the GUEPAR and HSS score 77.2 +/- 2.3 were very similar. Using unilateral weight-bearing X-rays, 18.8p. 100 demonstrated opening from ligament laxity and 40.6p. 100 had radiolucent lines under the components, which was the same as in the control group. The tibio-femoral mechanical axis using long-leg films had a mean varus angle of 0.7 degrees. PMID- 1306579 TI - [Post-operative iatrogenic hallux varus. Surgical treatment. Apropos of 19 cases]. AB - The post operative iatrogenic hallux varus associates varus, big toe's dorsal flexion and supination. The pathogeny is dominated by musculo-tendinous lack of balance created by the initial operation and excessive exostosectomy. The authors have nineteen times surgically corrected this deformation. The procedure included in all cases, a medial arthrolysis; five times associated with a screwed capito metatarsal osseous shelf (or graft) (when there was a metatarsal's head maiming); thirteen times associated with a metatarso-phalangeal arthrodesis (in cases of impaired joint surfaces). The authors analyse, besides, without excluding them the other surgical procedures for hallux varus, and particularly tendinous transfers. The results show the necessity of a perfect etiopathogenic analysis of the deformation. PMID- 1306580 TI - [Old fractures of the lateral humeral condyle (lateralis capitellum humeri) in children]. AB - The authors report their experience of 19 cases of non recent fractures of the lateral humeral condyle in children. The delay from the initial trauma to the first clinic was: minimum, 45 days (this delay defines a non recent fracture), maximum 7 years. 18 patients sustained an operation, 15 non-unions and 3 malunions; 1 patient was not operated on. The mean follow-up was about 5 years. The authors have determined two groups of patients according to the delay of treatment, less or more than 6 months. In the first group, 13 procedures out 14 allowed fusion of the condyle without necrosis. In the second group, the severe malalignments of the elbow required a varus or a valgus osteotomy. PMID- 1306581 TI - [Spinal deformities in Marfan disease]. AB - Spinal deformities are frequent in Marfan's disease. 37 patients were examined at the average age of 11 years. 32 showed a spinal deformity. The treatment of the spinal deformity was a brace in 15 cases, surgery in 16 cases (including 5 cases after brace-failure). 7 cases were just followed-up without treatment. Bracing was efficient only for mild curves, this treatment was satisfying 4 times out of 11 with adequate follow-up. The surgical treatment in 16 cases was a posterior fusion twice associated with anterior fusion. We used the same technique as for idiopathic scoliosis with Harrington instrumentation 5 times, Harrington with sublaminar wires 4 times and Cotrel-Dubousset instrumentation 7 times. The correction of scoliosis was achieved in 48.2 per cent. The use of segmental instrumentation compared with the use of the Harrington instrumentation can explain the small number of non unions and the improvement of the lateral spinal balance. We did not note any cardiovascular complication during or early after the operation. Aortic lesions were responsible of one death in the long term, three patients went through a surgical replacement of aortic valves or the aorta. PMID- 1306582 TI - [Surgical treatment of spinal deformities in Duchenne muscular dystrophy]. AB - Forty seven Duchenne Muscular Dystrophy patients, operated on for spinal deformity with segmental spinal instrumentation according to Luque's technique, are reviewed with a mean post-operative follow up of 4 years 4 months. The study of the results obviously showed the interest of Luque Galveston technique for the treatment of severe curves with pelvic obliquity, whereas Dove's rectangle is an interesting choice for the early instrumentation. A total spinal arthrodesis can probably be avoided in these patients, which often demonstrate a satisfying spontaneous fusion after instrumentation. The general and mechanical complications are described, according to the consequences they have on the management technique of these patients. PMID- 1306583 TI - [Preoperative embolization of cervical bone metastasis with radio-controlled direct puncture]. AB - Surgery of vertebral hypervascular metastasis can take advantage of preoperative embolization to make the surgical procedure easier to perform. Usually, embolizations are executed by vascular tract. We report a case of one cervical metastasis located in C4 for which embolization was executed with direct puncture of the vertebra. This method has the advantage to be feasible whatever tumoral vascularization, and more particularly in case of departure of radiculo-medullary artery or any other cephalic vessel from the tumoral site. PMID- 1306584 TI - [Treatment of recurrent or neglected clubfoot by Ilizarov's appliance]. AB - Nine cases of severe, multioperated clubfeet in children and adolescent have been corrected with Ilizarov apparatus. The two first patients have been treated by midtarsal osteotomy plus progressive correction. One poliomyelitic foot have had a slide lengthening of Achilles tendon and a plantar release. Six did not have any open procedure. One ring and two half circles were linked by five threated rods, in order to allow multi axial correction. Seven wires were introduced in the bones; the correction was obtained in a mean time of two months, the device was maintained one more month, then replaced by a walking cast during one month. The results have been seven times satisfactory, with an average follow up of nineteen months after the end of treatment. We did not note any early complication. One more procedure have been performed for flexum of the toes. The ankle range of motion have always been the same as the preoperative one. PMID- 1306585 TI - [Apropos of ... ulnar translocation of the carpus after surgery of the rheumatoid wrist. Review of 54 cases]. PMID- 1306586 TI - [Pathological fractures in children. Round table of the French Society for Orthopedic Surgery and Traumatology. Salonique, 8-11 May 1991]. PMID- 1306587 TI - [Prevention of deep venous thrombosis and postoperative pulmonary embolism (general, gynecologic and orthopedic surgery). Consensus Conference. Organized by Public Health Hospitals of Paris, 8 March 1991, Paris]. PMID- 1306588 TI - [Proceedings of the 66th Annual Meeting of the French Society for Orthopedic Surgery and Traumatology. November 1991]. PMID- 1306589 TI - [A few reflexion themes on the method in therapeutic evaluation]. PMID- 1306590 TI - [Plasma lipids in reflex sympathetic dystrophy. A study apropos of 90 cases]. AB - Plasma levels of cholesterol, triglyceride, HDL-cholesterol, and apolipoproteins A1 and B were assayed in ninety patients (sixty-four male and twenty-six female) with reflex sympathetic dystrophy and in ninety controls matched for age, sex, and body mass index (BMI). No significant differences were found between the two groups for the proportions of patients with increased plasma cholesterol levels (6.6% versus 4.4%) or increased plasma triglyceride levels (40% versus 30%), as defined by Turpin's age and sex-specific criteria, or for mean values of these parameters. In the 38 patients with reflex sympathetic dystrophy of less than 3.5 months duration, plasma triglyceride levels were significantly higher than in the 38 matched controls (1.24 + 0.57 g/l versus 1.02 +/- 0.91; p = 0.04). In patients (n = 52) with disease of more than four months duration (range 4-39), plasma triglyceride levels were similar in the two groups. Lipidemia was similar in patients and controls regardless of age, sex, topography of the disease, clinical manifestations, and whether or not the disease was due to an injury. This study, in contrast to previous reports, failed to disclose an association between reflex sympathetic dystrophy and hyperlipidemia. Transient hypertriglyceridemia may occur during the first 3 1/2 months of the disease as a result of initial immobilization. PMID- 1306591 TI - [Coccygodynia: value of dynamic lateral x-ray films in sitting position]. AB - In coccygodynia, pain is most severe in the sitting position. This prompted a study comparing lateral roentgenograms of the coccyx taken with the patient lying on the side. In this prospective study, eight of 30 patients had posterior subdislocation of the coccyx which caused pain and was visible only on the films taken in the sitting position. PMID- 1306592 TI - [Candida tropicalis arthritis of the shoulder associated with articular chondrocalcinosis]. AB - A case of infection of the scapulohumeral joint following articular infiltrations is reported in a female patient with alcohol-related cirrhosis of the liver. Joint destruction occurred despite appropriate treatment with fluconazole. Candida tropicalis joint infections are seen mainly in immunocompromised hosts and usually cause little destruction of the joint. Most are the result of dissemination via the bloodstream. Preexisting chondrocalcinosis in the patient reported here may have been a contributing factor to the development of extensive joint destruction. PMID- 1306594 TI - [Persistent pain following discal sciatica: reflex sympathetic dystrophy, an unusual complication to be examined. Apropos of 4 cases]. AB - Four patients who developed unilateral reflex sympathetic dystrophy of a lower limb associated with a bout of sciatica due to lumbar disc herniation are reported herein. In two cases, reflex sympathetic dystrophy developed after resolution of the sciatica, whereas the two conditions were concomitant in the two other patients. In all four patients, the diagnosis of reflex sympathetic dystrophy was missed. Surgery to release the root was considered in two cases. The reflex sympathetic dystrophy resolved within 1 to 3 months in every case. In view of the incidences of these two conditions, their concomitant occurrence seems rare. To avoid unwarranted therapeutic procedures, reflex sympathetic dystrophy should be considered in patients with chronic painful manifestations accompanying root involvement. PMID- 1306593 TI - [Meningeal melanocytoma or multiple pigmented meningioma of the spinal canal. Report of a case. Review of the literature]. AB - In a 64-year-old male with pain and weakness of the right lower limb, investigations disclosed a cervical tumor, several dorsal tumors, and tumoral infiltration of the lumbosacral area. Histological and, above all, immunohistochemical and ultrastructural features were suggestive of meningeal melanocytoma. Before the use of immunohistochemical and electron microscopy techniques, meningeal melanocytoma was designated by the term pigmented meningioma because its histological features bear some resemblance to those of meningioma. However, only a few cases of meningeal melanocytoma have been documented by immunohistochemistry and electron microscopy. Previously reported patients with meningeal melanocytoma had solitary tumors. In contrast, a review of the literature showed that multiple intraspinal or intraspinal and intracranial meningiomas are not exceptional, although meningiomatous infiltration is considerably less frequent. Treatment of such cases rests on surgery, radiotherapy, and chemoimmunotherapy. PMID- 1306596 TI - [Lupus, sicca syndrome and chronic interstitial nephritis. Apropos of a case]. AB - A female patient from the French Antilles developed renal failure due to pure chronic interstitial nephritis six months after the onset of systemic lupus erythematosus (SLE) for which she was taking hydroxychloroquine. Over time, results of biologic tests became suggestive of concomitant Gougerot-Sjogren syndrome, but neither the clinical nor the histologic findings were consistent with this diagnosis. The diagnosis of overlap syndrome between SLE and Gougerot Sjogren syndrome was established only six years later when the patient developed ocular and oral sicca syndrome with enlargement of the parotid glands. PMID- 1306595 TI - [Polyarthritis revealing hairy cell leukemia]. AB - A female patient simultaneously developed hematologic evidence of hairy cell leukemia and marked but short-lived inflammatory involvement of a number of joints. Both these groups of symptoms resolved simultaneously and rapidly under alpha-2 interferon therapy. This course suggests that the arthritis was a rheumatologic manifestation of the hematologic disease. The concomitant occurrence in this patient of arthritis, splenomegaly and leukopenia was suggestive of Felty syndrome: these two conditions need to be differentiated. PMID- 1306597 TI - [Arthritis and polyenthesitis after viral pleuro-pneumopathy due to Coxsackie virus]. AB - A sixty-one year-old male developed subacute polyenthesitis one month after the onset on pleuropulmonary disease. This last manifestation resolved completely six months later, whereas the enthesopathy ran a subacute course, improving over time. Three years after onset, the patient had monoarthritis of the left elbow and tendinitis of both Achilles tendons. During the course of the disease, neutralizing antibodies against Coxsackie virus A9 rose significantly then returned to normal when clinical manifestations improved. This finding suggests that viral infections may cause enthesopathy. PMID- 1306598 TI - [Bone and visceral manifestations of lipoatrophic diabetes. Apropos of a case]. AB - Lipoatrophic diabetes, known by pediatricians as Lawrence-Seip disease or Berardinelli lipodystrophy syndrome, is an infrequent condition of which approximately one hundred cases have been published to date. A case in a 24-year old female with a fifteen-year follow-up is reported. Manifestations included acanthosis nigricans, generalized lipoatrophy, hirsutism, muscle hypertrophy, and intellectual impairment. Biologic tests revealed insulin-resistant diabetes mellitus with major diet-dependent type V hypertriglyceridemia. The patient had nephrotic syndrome (focal and segmental endocapillary proliferative glomerulonephritis without dense deposits). Phosphorus and calcium determinations were normal, as were the endocrinologic tests. Roentgenograms of the bones disclosed increased density of axial bones and large epiphyseal defects with increased bone density as determined by osteodensitometric studies. The bone manifestations of this syndrome have been documented but are often overshadowed by the severe metabolic alterations. PMID- 1306599 TI - [Parsonage-Turner syndrome complicated by sympathetic dystrophy syndrome with adhesive capsulitis of the shoulder. Apropos of 2 cases]. AB - Two typical cases of Parsonage-Turner syndrome with reflex sympathetic dystrophy syndrome and adhesive capsulitis of the shoulder are reported. The rarity of this combination is discussed. PMID- 1306600 TI - [Comparative efficacy of ketoprofen related to the route of administration (intramuscular or per os). A double-blind study versus placebo in rheumatoid arthritis]. AB - Evidence of the analgesic effects of nonsteroidal antiinflammatory drugs in human diseases is easy to collect. However, demonstration of differences in the activity of NSAIDs according to the route of administration is considerably more difficult. Forty patients with rheumatoid arthritis were given either one intramuscular injection of 100 mg ketoprofen with two placebo capsules or one intramuscular injection of placebo with two 50 mg ketoprofen capsules. Analysis of changes in pain severity over the six-hour study period failed to disclose any statistically significant differences between the two groups. However, time to peak effectiveness (Tmax) was significantly shorter with the intramuscular route (194 +/- 118 minutes) than with the oral route (276 +/- 111 minutes) (p = 0.029). Although intramuscular NSAID therapy is rarely warranted in RA patients, these findings suggest that RA may serve as a clinical model for evaluating the effectiveness of a NSAID according to the route of administration. PMID- 1306601 TI - [Dermatopolymyositis and D-penicillamine: value of the search for anti-JO1 antibodies]. PMID- 1306602 TI - Long-term results of pylorus-preserving gastrectomy for gastric ulcer. AB - The postoperative results of pylorus-preserving gastrectomy (PPG) for gastric ulcer performed in 134 patients during the past 25 years (mean postoperative period, 16.6 years) were studied. The incidence of postoperative complications was low. Dumping syndrome occurred in only 4.4% and 0% of cases as assessed by questionnaire and interview, respectively. Four (5.4%) of 74 patients available for this study had ulcer recurrence. In one of these four patients concurrent gastroduodenal ulcer was suspected from preoperative gastric analysis. The site of recurrence was found in all cases to be the remnant antral gland area along the greater curvature between the proper gastric gland area and the duodenum. Basal and maximal acid outputs at the time of relapse were significantly higher in patients with recurrence than in patients without recurrence. The fasting and postprandial serum gastrin levels were high in one patient with recurrence, whose antrum was preserved as long as 3 cm proximal to the pyloric ring; this was longer than that described in our original method of PPG. In two other recurrent cases the serum gastrin levels were not different from those in nonrecurrent cases. Immunohistochemical examination of the residual antrum showed no increase in the G-cell density in patients either with or without recurrence. These results suggest that the long-term quality of life of patients treated with PPG remains favorable. Recurrence rate can be further reduced if PPG is strictly indicated for gastric ulcer only and carried out by meticulous surgical techniques. In the pathogenesis of the ulcer recurrence the role of gastrin release from the residual antral mucosa seems to be limited. PMID- 1306603 TI - Immunohistochemical study of the sympathetic and sensory innervation to the blood vessels of the dog forepaw. AB - Immunohistochemical staining of arteries supplying the dog forepaw showed a dense distribution of nerve fibers which were immunoreactive to tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) around the vascular walls. The density of each immunoreactive fiber tended to increase in the peripheral branch of the vascular tree. Retrograde axonal tracing with Fast Blue from the artery revealed that these immunoreactive fibers originated from NPY-containing catecholaminergic as well as VIP/SP/CGRP-containing non-catecholaminergic neurons in the stellate ganglion and SP/CGRP-containing neurons in the dorsal root ganglia of segments C7 to Th1. After stellate ganglionectomy, TH-, NPY-, and, VIP immunoreactive fibers disappeared completely from the arterial walls while approximately 40% of SP- and CGRP-immunoreactive fibers remained. The present results indicate that the artery of the dog forepaw receive triple innervation of adrenergic sympathetic, non-adrenergic sympathetic, and sensory fibers, and suggest that about 40% of SP- and CGRP-immunoreactive fibers are of sensory origin. PMID- 1306604 TI - Purification of a new anticoagulant protein, calphobindin III, from human placenta. AB - The Ca(2+)-phospholipid binding proteins in human placental tissue were investigated with the binding of a placental EDTA extract to liposomes composed of placental phospholipids. A new Ca(2+)-dependent phospholipid-binding protein different from calphobindin I (CPB I) and calphobindin II (CPB II) was isolated from the EDTA extract, and the purification procedure of this protein was established. The yield of the purified protein was about 1.2 mg from one placenta. The protein prolonged the clotting time of normal plasma when coagulation was induced by tissue factor and ellagic acid. This protein had an apparent molecular weight of 32,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions, and its isoelectric point was 5.8. Because of its ability to bind phospholipids in the presence of Ca2+, this protein was designated as calphobindin III (CPB III). PMID- 1306605 TI - Changes of fibronectin in the right and left ventricles of rats exposed to chronic normobaric hypoxia. AB - Changes of fibronectin (FN) in the right and left ventricles of adult rats exposed to chronic normobaric hypoxia were observed by a peroxidase immunohistochemical stain technique and analyzed quantitatively by a point counting method. Fifty-six rats were randomly divided into control groups of day 0 (immediately prior to the experiment), day 5, day 15, and day 30 and hypoxia groups of day 5, day 15, and day 30. Rats of the hypoxia groups were put into a normobaric hypoxia chamber with oxygen concentration adjusted to 10 percent. The rats of the control groups breathed room air. From day 5 on, the ratio of the weight of the right ventricle (RV) to that of the left ventricle (LV) plus interventricular septum (SP), RV/(LV+SP), and the ratio of the weight of the right ventricle (RV) to the body weight (BW), RV/BW, in the hypoxia groups increased significantly as compared with those of the control groups. The amount of immunoreactive FN in the right ventricle increased significantly in the hypoxia groups after exposure to hypoxia environment for 15 days (10.31% +/- 2.15%, mean +/- S.D.) and for 30 days (9.55% +/- 1.65%) as compared with those in the day 0 control group (3.05% +/- 1.15%, p < 0.01), the day 15 control group (3.26% +/- 0.83%, p < 0.01), and the day 30 control group (3.19% +/- 0.51%, p < 0.01). However, there were no significant changes in the amount of immunoreactive FN in the left ventricle of the hypoxia groups as compared with the control groups. These results suggest that chronic hypoxia may lead to an increase of FN in the hypertrophied right ventricle but not in the left ventricle, which indicates that pulmonary hypertension induced by chronic hypoxia rather than chronic hypoxia itself is a major cause for the increase of FN in the myocardium. The increased FN in the right ventricle may accelerate the accumulation of collagen and, in turn, contribute to the increase of the myocardial stiffness and eventually to the diastolic dysfunction of the hypertrophied right ventricle induced by chronic hypoxia. PMID- 1306606 TI - Methods of semen preparation for intrauterine insemination and subsequent pregnancy rates. AB - Semen for insemination, either intrauterine or in vitro, must be prepared to remove seminal plasma products and/or select the healthier population of sperm prior to use. Traditionally, a double wash technique is performed, with or without subsequent swim-up to isolate the motile fraction if necessary. More recently, the use of the SperPrep filtration method has gained acceptance, with the benefits of removal of leukocytes and seminal debris from the specimen as well as enhancement of overall sperm quality. In the current study we compared the traditional double wash method without the swim-up to Sperm-Prep filtration. Intrauterine inseminations (IUI's) were performed in 307 cycles on 148 infertile couples at two different infertility centers in the USA. After complete diagnostic evaluation the couples were offered IUI before proceeding to any other form of assisted reproductive technologies. Semen samples were prepared in human tubal fluid media supplemented with 5% human serum albumin (HSA; location 1) or in Ham's F-10 media supplemented with 3% HSA (location 2), either with the SpermPrep filtration method (ZBL, Inc., Lexington, KY 40523, USA) or the double sperm wash (SW) procedure. Similar sperm numbers were used for the IUI procedure in both treatment groups and locations. The Sperm-Prep method resulted in significantly higher pregnancy rates (PR) than the SW procedure, independent of location. The clinical pregnancy rates per cycle were statistically lower (p < 0.05) in the SW group (20-22% vs. 9-10%). Of significant clinical importance, almost twice as many cycles were required in the SW group to achieve these pregnancies when compared to the SpermPrep group of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306607 TI - Locoregional control for esophageal carcinoma treated with irradiation following surgery. AB - Locoregional failure was analyzed in a total of 34 esophageal carcinoma patients treated with postoperative prophylactic irradiation following curative surgery. All patients had squamous cell carcinoma and no prior treatment. Twelve patients had subsequent lymph node metastasis in the follow-up period. In the 12 patients with node metastasis, there were 5 instances of supraclavicular node metastasis, 7 instances of thoracic inlet node (uppermost part of mediastinum) metastasis, and 3 instances of mediastinal node metastasis. Three patients had 2 metastatic nodes and 9 patients had 1 metastatic node. Intervals between surgery and recurrence were a median of 12 months for mediastinal nodes, 19 months for thoracic inlet nodes, and 26 months for supraclavicular nodes. Ten (52.6%) of the 19 patients treated by using a 12-MeV electron beam had metastatic involvement at the supraclavicular and thoracic inlet nodes. On the other hand, 2 (13.3%) of the 15 patients had the above-described lymph node metastases when treated by using 15-MeV electron, 18-MeV electron, or 10-MV photon beams. The difference in the metastatic rate between these two groups was statistically significant at the level of p < 0.05 (chi-square test); this seems to be attributable mainly to the dose level at deep region. Doses of over 50 Gy to the thoracic inlet and supraclavicular nodes at deep location were necessary to reduce metastasis. PMID- 1306608 TI - Eucapnic hyperventilation-induced bronchoconstriction in rabbits. AB - We examined whether eucapnic hyperventilation with dry air produces the bronchoconstriction in anesthetized, non-sensitized rabbits and in ovalbumin sensitized rabbits. Eucapnic hyperventilation challenge with dry air containing 5% CO2 at room temperature was performed with 4 non-sensitized and 7 sensitized rabbits by mechanical ventilation for 15 min (120 breaths/min, 7 ml tidal volume/kg body weight). Total lung resistance (RL) and dynamic compliance (Cdyn) were measured before and 0, 5, 15, and 30 min after hyperventilation. In non sensitized rabbits, RL and Cdyn did not change significantly. However, in sensitized rabbits, RL increased maximally by 48.9% +/- 9.0% at 5 min, and then decreased to the baseline level at 30 min after challenge. Cdyn decreased maximally by 12.5% +/- 3.5% at 15 min after challenge. These changes were significantly different from the baselines (p < 0.05). Furthermore, to investigate the role of histamine on hyperventilation-induced bronchoconstriction (HIB) in sensitized rabbits, we performed the hyperventilation challenges in 5 sensitized rabbits with the pretreatment of H1-receptor antagonist (chlorpheniramine, 1 mg/kg, i.v.) and found that the maximum increment of RL was suppressed to 24.2% +/- 7.4% of the control, which was significantly lower than the maximal RL in nontreated sensitized rabbits (p < 0.05). We concluded that HIB occurs only in sensitized rabbits and that histamine may play an important role in the development of HIB in sensitized rabbits. PMID- 1306609 TI - Effect of methylene blue on the vesicourethral function in the rats. AB - The bladder and urethral activities during the rhythmic bladder contractions were evaluated before and after the intraarterial administration of methylene blue, which prevents the activation of soluble guanylate cyclase. The methylene blue produced an increase in the bladder activity and a decrease in the urethral smooth muscle relaxant response induced with bladder contraction. The L arginine/nitric oxide pathway seems to modulate the vesicourethral function. PMID- 1306610 TI - Making the World Health Organization work: a legal framework for universal access to the conditions for health. AB - Improving global health conditions has been one of the most important and difficult challenges for the world community. Despite concerted efforts by international organizations, like the World Health Organization, great disparities in health conditions remain between developed and developing countries, as well as within those countries. The World Health Organization has achieved some successes through its Health for All strategy; however, it can and should encourage member nations to enact national and international laws to protect and promote the health status of their populations. A comparison to the lawmaking efforts in other areas by international organizations indicates that WHO may have the authority and the means to institutionalize efforts to improve global health conditions. PMID- 1306611 TI - The Estelle medical professional judgment standard: the right of those in state custody to receive high-cost medical treatments. AB - This Article discusses the rights of prisoners, pretrial detainees, and the involuntarily committed to receive high-cost medical treatments. More specifically, the Article analyzes U.S. Supreme Court and lower court case law dealing with the medical care rights of those in state custody and argues that, under a proper understanding of this case law, the financial considerations of states should play no role in determining the rights of these people to receive high-cost medical care. Finally, the Article defends the current medical care standard against various critiques. PMID- 1306612 TI - Aid-in-dying: should we decriminalize physician-assisted suicide and physician committed euthanasia? AB - Recent news stories, medical journal articles, and two state voter referenda have publicized physicians' providing their patients with aid-in-dying. This Note distinguishes two components of aid-in-dying: physician-assisted suicide and physician-committed voluntary active euthanasia. The Note traces these components' distinct historical and legal treatments and critically examines arguments for and against both types of action. This Note concludes that aid-in dying measures should limit legalization initiatives to physician-assisted suicide and should not embrace physician-committed voluntary active euthanasia. PMID- 1306614 TI - [The role of electrochemical techniques in the understanding of the mechanism of drug actions. Example of an anti-Bilharzia agent]. AB - In order to gain an interpretation of the schistosomicidal effect of 4-methyl-5 (2-pyrazinyl)-1,2-dithiole-3-thione (Oltipraz), chemical, electrochemical and enzymatic hypotheses are discussed from a pharmacological standpoint. The enzymatic hypothesis is in good agreement with experimental results which ascertain that Oltipraz behaves as a prodrug. PMID- 1306613 TI - Pushing the environmental regulatory focus a step back: controlling the introduction of new chemicals under the Toxic Substances Control Act. AB - Environmental destruction and its attendant effects on the animal world, including human beings, has moved to the forefront of United States and worldwide policy. The effect of this deterioration on human health is unclear. Much debate focuses on the cases of cancer, along with other diseases, that are environmentally induced. Congress has responded with various environmental laws. These laws focus primarily on controlling chemicals placed into the environment, largely by industry. This Note proposes that such a singular focus is inadequate and ultimately costly. A more sensible and efficient strategy to environmental protection places emphasis on controlling inputs to the productive process before the need arises to contain such substances. The Toxic Substances Control Act of 1976 ("TSCA") takes this approach. This Note reviews the means by which TSCA attempted to accomplish its goals and concludes that TSCA's implementation has largely been ineffective. The Note then discusses three possible explanations for TSCA's failure. Finally, the Note proposes how TSCA might be made more effective in regulating new chemicals. PMID- 1306615 TI - [Contribution of capillary electrophoresis in the analysis of molecules with pharmaceutical and biotechnological value]. AB - Capillary electrophoresis entails a variety of separation modes which are: capillary zone electrophoresis, capillary gel electrophoresis, micellar electrokinetic capillary chromatography, isoelectric focusing and isotachophoresis. Many applications are already reported. The fundamentals of the various modes are discussed along and typical separations in the pharmaceutical and biotechnologic fields are presented. The advantages and disadvantages in comparison to other analytical techniques are also discussed. PMID- 1306616 TI - [Multiparameter analysis of pharmacological specificity of 3-benzylchromone (homoisoflavone) derivatives on different pharmacological tests in vitro]. AB - For access to structure/activity/specificity of a serie of eight 3 benzylchromones (homoisoflavones), the authors used multivariate analysis. The obtained results allow to envisage the synthesis of molecules more specific of one of the three types of activities studied: angioprotective, antihistaminic, antiallergic. PMID- 1306617 TI - [Study of the turnover or the release of brain dopamine in rats after administration of N-linoleyl dopamine]. AB - Wistar male rats received N-linoleyl dopamine (L-DA) at doses of 10, 50 or 100 mg/kg (i.p.). 2 h after these injections they were decapitated and dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), as well as the ratio DOPAC/DA, which could represent the DA turnover, were determined in the striatum, the frontal cortex or the hypothalamus, while homovanillic acid (HVA) as well as the ratio HVA/DA, which could represent the DA release, were determined in the striatum by high performance liquid chromatography (HPLC). Except a small rise of DA and DOPAC in the hypothalamus, at high L-DA doses, no significant modifications in DA, DOPAC, DOPAC/DA, HVA or HVA/DA were observed in the other brain areas studied. These results, in good agreement with the recent data obtained with other dopaminergic agonists, could show the absence of correlation between the hypomotility, on the one hand and the decreasing of the turnover or the release of the brain DA, on the other hand. Together with the data obtained recently by scandinavian and italian authors, they could raise questions about the position and the role of dopaminergic autoreceptors. PMID- 1306618 TI - [Correlations between the different criteria of late potentials and results of programmed ventricular stimulation after myocardial infarction]. AB - Five to ten per cent of survivors of acute myocardial infarction die within two years. The majority of these deaths are sudden and are attributed to a lethal ventricular arrhythmia. This is usually ventricular tachycardia degenerating to ventricular fibrillation. These post-infarction tachycardias are generally due to reentry. They require an anatomic arrhythmogenic substrate, a zone of delayed conduction. This can be detected as late potentials on signal averaged ECG. The triggering of a significant ventricular arrhythmia by ventricular stimulation is closely correlated to the occurrence of a severe ventricular arrhythmia in the months following infarction. Programmed ventricular stimulation could, therefore, help to identify patients requiring close follow-up and/or preventive antiarrhythmic therapy, but cannot be offered to all patients because of its invasive nature. Seventy nine post-infarction patients were studied prospectively. All underwent coronary angiography, signal averaging electrocardiography, and programmed ventricular stimulation at least 15 days after infarction. Fifty five patients had at least one criterion of late potentials (QRS duration > or = 110 ms and/or amplitude of the last 40 ms < 27 microV and/or duration of potentials of under 40 microV > 37 ms). Twenty four patients had no late potentials. The results of programmed stimulation were estimated to be positive when sustained or unsustained monomorphic ventricular tachycardia was triggered, and negative when ventricular fibrillation, ventricular flutter unsustained polymorphic ventricular tachycardia or no arrhythmia could be induced. Programmed ventricular pacing triggered 15 significant events, 17 unsustained polymorphic ventricular tachycardias, 13 ventricular flutters and 11 ventricular fibrillations. The exploration was negative in 23 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306619 TI - [Holter monitoring of ventricular arrhythmia during the 24 first hours of myocardial infarction treated with intravenous thrombolysis]. AB - The aim of this study was to assess ventricular arrhythmias after intravenous thrombolysis for acute myocardial infarction and to determine their relationship with coronary artery patency. A 24 hour Holter recording was started 3.1 +/- 0.2 hours after the onset of pain in 40 patients (age 54 +/- 1.6 years, 42.5% anterior infarcts) treated by streptokinase (42.5%) or tissue plasminogen activator (57.5%) within 3.3 +/- 0.2 hours of the beginning of symptoms. The arrhythmias were analysed on a Marquette 8000 computer. Coronary angiography was systematic and was performed 26.7 +/- 2.5 hours (within 4 hours in 60% of patients) after the onset of pain to define coronary artery patency (TIMI 2 and 3: 72.5%) or occlusion (TIMI 0 or 1: 27.5%). Ventricular arrhythmias were common and generally well tolerated (one defibrillation for ventricular fibrillation). Accelerated idioventricular rhythms and ventricular tachycardias were equally prevalent in patients with patent arteries (90% and 83%) as with occluded arteries (82% and 73%). The prevalence of sustained ventricular tachycardias (> 15 complexes) and of early accelerated idioventricular rhythms (< or = 6 hours) was significantly higher in patients with patent coronary arteries: 38% versus 0% (p < 0.05) and 76% versus 18% (p < 0.01). These arrhythmias may be considered to be non-invasive markers of early coronary reperfusion, with a sensitivity of 38 and 76% and a specificity of 100 and 82%. Coronary patency was associated with higher numbers of ventricular extrasystoles, ventricular tachycardias and accelerated idioventricular rhythms by a factor of 14, 13 and 32 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306620 TI - [Anatomoclinical study of 100 cases of hypoplasia of the right ventricular muscle (including 89 unexpected sudden deaths). Relation with Uhl's anomaly]. AB - The authors present the pathologist's view of Uhl's anomaly based on 100 cases recorded over 31 years, 89 of which came from medico-legal autopsies following sudden unexpected death in young subjects. The anatomic diagnosis is made by macroscopic examination of the whole heart in diffuse forms (parchment heart) and from transverse sections of the mid third of the ventricle in incomplete forms, showing absence of myocardium in the juxta-septal anterior wall of the right ventricle. The wall entirely made up of adipose tissue, may retain its normal thickness. On microscopy, normal adipose tissue is observed between the epicardium and endocardium, sometimes with islets of myocardium dispersed in the subendocardial layer and with, in about half the cases, subendocardial bundles of non-hyalinized collagen without any inflammatory cellular infiltration. Other structural histopathological lesions may complicate the malformation, involving the intraseptal arterioles or the conductive system. In addition to the 89 cases of sudden and unexpected death before the age of 50 (preceded by some modification of the patient's life style in 29 cases), 11 cases were symptomatic and 5 were transplanted with a good result. The clinical diagnosis of Uhl's disease is important because of its consequences: ventricular tachycardia and possible sudden death, more rarely cardiac failure with age. Histological analysis should take into account the constant presence of adipose tissue in the right ventricle, and should only interpret excessive quantities with associated myocytic aplasia as pathological.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306621 TI - [Percutaneous mitral valvulotomy: comparison of 2 techniques in 100 matched-pair patients]. AB - The results of percutaneous mitral valvulotomy by the Double Balloon and the Inoue Balloon were compared in 100 patients referred to Marie-Lannelongue Hospital between 7/11/86 and 8/3/91, paired for age, sex and echocardiographic features of the mitral valve. The transvalvular diastolic pressure gradient at catheterisation or Doppler echocardiography decreased significantly and similarly with the two techniques: -65 +/- 19% versus -64 +/- 15% (p = 0.10) and -66 +/- 22% versus -58 +/- 23% (p = 0.20) for the Double-Balloon and the Inoue Balloon techniques respectively. Similarly, the mitral valve surface area measured by planimetry during echocardiography or calculated from the Gorlin formula increased by 0.9 +/- 0.39 cm2 with the Double Balloon and by 0.88 +/- 0.32 cm2 with the Inoue Balloon (p = 0.91) or by 0.98 +/- 0.62 cm2 versus 0.87 +/- 0.45 cm2 (p = 0.42). The number of commissures opened was the same with both techniques. The evolution of mitral regurgitation after dilatation was similar: stable or less severe in 61% dilated by the Double Balloon and 68% by the Inoue Balloon; aggravation by more than one grade in 7 and 5% respectively (p = 0.17). Complications were rare and comparable with both techniques. The results with the two methods were the same if patients with an optimal indication and those with more severe mitral valve disease were considered separately. The rapidity and simplicity of percutaneous mitral valvulotomy with the Inoue Balloon make it the technique of choice. PMID- 1306622 TI - [Current role of intra-aortic diastolic balloon counterpulsation in heart surgery]. AB - Intra-aortic balloon counterpulsation (IABP) is a relatively non-invasive method of circulating assistance, easy to use and which has benefitted from a number of technological improvements in recent years. This retrospective study over 4 years was undertaken to analyse the results of IABP and to determine its role in therapeutic arsenal against cardiac failure. Sixty five patients, 57 coronary and 8 valvular cases, with an average age of 61 +/- 10 years were included. The indications of IABP were: a bridge to transplantation (3 cases), complications of coronary angioplasty (4 cases), and low cardiac output after cardiopulmonary bypass (58 cases), where IABP was curative in 85% of cases and prophylactic in 15% of cases (patients with risk factors of low output state after CPB). Beforehand, 65% of patients had poor left ventricular function (LVEF < 40% and/or CI < 2.2 l/mn/m2). An Aries Medical M700 console was used. The percutaneous femoral approach was feasible in 87% of cases. The results were: improvement with discharge from intensive care unit in 60% of cases, transient improvement in 7% of cases, no improvement in 15% of cases and cardiac transplantation in 8% of cases. The outcome was worse when the preoperative LV function was poor and when high dose inotropic agents had to be used. Survival was 100% in those patients in whom IABP was a prophylactic measure. The average duration of IABP was 72 hours, survival being significantly lower in those in whom IABP was continued for over 3 days. The complications (12.7%) were thromboembolic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306623 TI - [Prevalence and description of cardiac involvements in primary antiphospholipid syndrome]. AB - In order to assess the prevalence of cardiac involvement in the primary antiphospholipid syndrome (PAS), a syndrome which associates thromboembolism, recurrent abortion, the presence of antiphospholipid antibodies and thrombocytopenia, transthoracic (TTE) and trans-esophageal echocardiography (TEE) was performed in 15 patients, 10 women and 5 men with a mean age of 38.8 +/- 11 years, with the PAS but without systemic lupus erythematosus. The presentation of the PAS was a thrombotic event (6 arterial and 7 venous) in 13 cases, and recurrent abortion in 3 cases. Twelve patients had high anticardiolipin antibody levels (> or = 15 U GPL) and 12 had a raised anti-prothrombinase antibody title. Valvular heart disease was detected in 9 patients (60%) as a valve thickening (> or = 5 mm for the mitral and > or = 3 mm for the aortic valve) or nodule. Mitral regurgitation was observed in 4 cases both on TTE and TEE and was mild in 3 cases and severe in 1 case. Aortic regurgitation was diagnosed in 6 patients, in 3 cases by TTE and in 6 cases by TEE. It was mild in 5 cases and moderate in the other cases. Pericardial effusion was observed in 3 patients (20%), alone in 1 case and associated with valvular disease in the other two cases. No abnormality of left ventricular systolic or diastolic function could be demonstrated. In conclusion, cardiac involvement seems to be common in the PAS, and TEE is a sensitive and accurate method for describing the valvular, especially aortic valve, abnormalities. PMID- 1306624 TI - [Evaluation of the size of thrombolysed myocardial infarction by serum myosin determination]. AB - The prognosis of myocardial infarction is very dependent on the size of the infarct. The measurement of the infarct size after thrombolysis remains difficult despite the large number of methods available, all of which have drawbacks. This parameter is however essential to assess prognosis and the efficacy of thrombolytic therapy. Serum beta heavy chain myosin determination is a recently introduced method of evaluating infarct size; there are relatively few published studies, especially concerning post-thrombolytic patients. A prospective study was undertaken in 40 patients (37 men and 3 women: average age 55.6 years) with a primary myocardial infarction treated by thrombolysis. Myosin levels (peak and area under curve of 5 samples in 10 days) were compared with other methods of assessing infarct size: electrocardiogram (number of leads with Q waves, ST segment analysis), cardiac enzymes (peak and release integrals of CK abd LDH), contrast ventriculography (segmental asynergy score, ejection fraction), coronary angiography and resting MIBI myocardial scintigraphy. The peak and integral of myosin release correlated well with the other methods (p < 0.01): a correlation was particularly apparent between the integral of myosin release and MIBI scintigraphy scores (r = 0.77, p < 0.001). Complex myosin release kinetics were observed significantly more often in patients with large infarcts (p < 0.01) or in those with occlusion of the artery responsible for infarction at coronary angiography on the 6th day (p = 0.001). In conclusion, with 5 blood samples over a 10 day period, it is possible to estimate the infarct size after thrombolysis in everyday cardiological practice: this method could help identify high risk subjects (complex kinetics of myosin release and high peak myosin levels) and also could be used to assess efficacy of thrombolytic therapy in large scale trials. PMID- 1306625 TI - [Cardiology in general hospitals. A cooperative survey on medical teams, technical means and activity]. AB - A national enquiry carried out in 1990 in the departments of cardiology of general and private non-profit making hospitals established the status of these departments and the evolution of their personnel and equipment since their creation. The enquiry involved two thirds of the cardiology departments of the general hospitals (119/180) and showed that most (66%) were established between 1974 and 1988. Implanted in fairly important cities with catchment areas of 100,000 to 400,000 people, they have an average of 32 beds (range 11 to 100) and 7.25 coronary care beds (range 4 to 19); 347 doctors work full (211) or part time (136) in these departments. These two types of work are allowed in the majority of these units (64/119). Specialist certified cardiologists practice in 62 departments (56%). The usual technical equipment is available in 80% of the units (Doppler echocardiography, exercise stress testing, Holter monitoring, right heart catheterisation). Permanent pacing is performed in 65% of these hospitals, more so in the provinces than in the Paris region. Coronary angiography is only available in 21%, radioisotopic investigations in 15% and coronary angioplasty in 12% of these centres. A prospective study performed in 1990 concerning 110 hospitals recruited 1,030 myocardial infarctions, which enabled the total number of infarcts hospitalised in the coronary care units of the general hospitals to be estimated at about 21,000 (60% of French myocardial infarctions). PMID- 1306626 TI - [Should mitral valve diseases, without or with few symptoms, be treated surgically?]. AB - Our approach to the treatment of valvular heart disease, and mitral valve disease in particular, has been deeply modified by the experience acquired since the introduction of cardiac surgery and the technical advances in this field in the last decade and by new methods of investigative and interventional cardiology. In pure severe mitral regurgitation alone, the treatment of choice is reconstructive surgery. In the experience of our group, 191 patients out of 342 operated since 1970 for this type of valve lesion were referred for reconstructive surgery. Taking the results into consideration (72% 15 year survival), it is now justified to refer patients at a stage when the valvular disease is asymptomatic or pauci symptomatic. A certain number of factors has to be assessed to evaluate the surgical indication: the experience of the surgical team, the etiology of the mitral regurgitation, the type of anatomical lesion, the stage of the cardiac disease and the patient's age. In mitral stenosis, in preference to surgical commissurotomy, percutaneous mitral valvuloplasty may be proposed in certain asymptomatic or pauci-symptomatic patients if the stenosis is severe, if the anatomical lesions are optimal and if there is a hemodynamic (pregnancy) or thromboembolic risk (arrhythmias, spontaneous contrast on transoesophageal echocardiography). In mixed mitral valve disease or very calcific stenoses, analysis of long-term results of valve replacement indicates that the late prognosis depends more on the stage of the cardiac disease at the time of surgery than on the type of prosthesis. It is advisable not to wait until an advanced stage before operating these patients when the valvular dysfunction is severe and there are hemodynamic consequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306627 TI - [Should asymptomatic aortic valve disease be treated surgically?]. AB - The problems posed by asymptomatic aortic valve disease with regards to surgery differ according to whether the lesion is aortic stenosis or regurgitation. In stenotic lesions, even severe, the risk of spontaneous evolution is very small when the subject is totally asymptomatic. However, the quality of the results of surgery in asymptomatic or pauci-symptomatic patients and the increased difficulties in the very elderly are incentives not to differ surgery when the stenosis is severe, and especially when left ventricular function begins to degrade. In aortic regurgitation, the risk of progression is also low in asymptomatic patients but left ventricular dysfunction may develop before symptoms occur: this explains the necessity for regular clinical, echocardiographic and eventually radioisotopic examination of patients with severe aortic regurgitation. In dystrophic aortic regurgitation, an aneurysm of the sinuses of Valsalva and/or of the ascending aorta, or progressive fusiform dilatation of the ascending aorta are reasons for not postponing surgery for replacement of the aortic valve and the ascending aorta. PMID- 1306628 TI - [Pro-arrhythmia effect of pyridostigmine. Apropos of a case]. AB - A coronary patient with myasthenia gravis with a previous myocardial infarction presented with severe ventricular arrhythmias after the replacement of neostigmine by pyridostigmine for the treatment of the myasthenia. These arrhythmias were resistant to antiarrhythmic therapy associating betablockers and amiodarone throughout treatment with pyridostigmine but regressed when this drug was withdrawn. A test of reintroduction of pyridostigmine under medical surveillance led to the reappearance of the ventricular hyperexcitability, so confirming the responsibility of this drug. This would seem to be the first reported case of severe ventricular arrhythmias due to a proarrhythmic effect of pyridostigmine. The possible mechanisms of this effect are discussed. PMID- 1306629 TI - [Myocardial infarction caused by thrombosis of the common trunk of the left coronary artery without collateral circulation. Treatment by intra-aortic counterpulsation and subsequent heart transplantation]. AB - The authors report the case of an acute anterior myocardial infarction due to occlusion of the left main coronary artery without a collateral circulation. The patient survived after intraaortic balloon pumping followed by cardiac transplantation. PMID- 1306630 TI - [Rupture and extravascular migration of a vena cava filter. Apropos of a case]. AB - The authors report the case of a 68 year old woman who underwent implantation of a Greenfield vena caval filter for recurrent pulmonary embolism. Migration of the filter out of the vena cava into the perivenal fat was discovered two years later during another embolic episode. One of the spokes of the filter had migrated into the iliac fossa. This case illustrates two possible complications of caval filters: rupture and migration. The increasing number of cases reported in the literature indicates the necessity of keeping a register of the complications encountered with different models to avoid the most dangerous ones. PMID- 1306631 TI - [Radiofrequency ablation of atrioventricular conduction during the 5th month of pregnancy]. AB - The authors report the case of radiofrequency ablation of atrioventricular conduction in a 5 months pregnant woman who had hypertrophic cardiomyopathy. The indication of this procedure was a poorly tolerated resistant supraventricular tachycardia with foetal distress. A dual-chamber rate-assisted pacemaker programmed in the VVIR mode was implanted during the same procedure normally, with normal delivery of a healthy child at 8 months' gestation. PMID- 1306632 TI - [Respiratory allergies in the Flegrean region]. AB - The Authors value 407 consecutive outpatients, with rhinitis, conjunctivitis and asthma, coming from Flegrean area. In the patients with prick test positivity for pollen or inhalants the results were compared with clinical symptomatology. The data obtained, confirm the importance of inhalants persistent in asthma, and the rilevance of seasonal pollens in rhinoconjunctivitis and episodic asthma. In this homogeneous population, never the olea positivity was demonstrated as a single, whereas ambrosia (ragweed) was founded. PMID- 1306633 TI - [Effects of transdermal nicotine as an adjunct in smoking cessation therapy. A double-blind randomized study controlled with placebo]. AB - To assess the smoking cessation efficacy of transdermal nicotine patches an adjunct to low-intervention therapy, we conducted a double-blind, placebo controlled trial in 158 smokers. Participants were randomly assigned to one of the following three study regimens that required daily application of two 15-cm2 patches: 1) 24-hour nicotine delivery, 2) nicotine delivery during wakeful hours only, and 3) placebo. The impact of the three regimens on smoking cessation rates and tobacco withdrawal symptoms was examined. During the last 2 weeks of the trial, 39% of the 24-hour nicotine regimen delivery group, 35% of those on wakeful hour nicotine regimens, and 13.5% of the placebo treatment group achieved abstinence. Self-reported quit rates for the two nicotine patch-wearing regimens, as compared with that for the placebo group, continued to be significantly higher at 6 months. Moreover, compared with placebo, the transdermal nicotine patches significantly reduced tobacco withdrawal symptoms during the first few weeks of quitting. The differences in quit rates and tobacco withdrawal symptoms between the to active groups were not statistically significant. The patches were well tolerated both topically and systemically. We concluded that transdermal nicotine, when used as an adjunct to low-intervention therapy, significantly reduced tobacco withdrawal symptoms and enhanced smoking cessation rates. PMID- 1306634 TI - [Quality of life and psychologic features of subjects with chronic respiratory diseases]. AB - The aim of this study is to verify the psychological attitude and the quality of life in patients suffering from chronic respiratory insufficiency. Taking for granted that a bad quality of life is connected with the symptom of a depressed state (loss of appetite, quality of sleep, sexuality, psychomotor slowing down, loss of energy, weariness, reduced interest for the external world, feelings of self-devaluation, reduced working and concentration capacity, complainings of turning over type) we have taken as index of "normal quality of life" the lack of these attitudes correlating them to the clinical symptoms and/or the patient's functional troubles and verifying how much they can affect the psychological features and how much the deterioration of the quality of life. For this reason a questionnaire, taken from the MMPI test (Minnesota Multiphasic Personality Inventory), restricted to the items related to the D scale (depression scale), has been given to one hundred COPD patients who had been examined previously from a clinical functional point of view. In the end, we have drawn our results both on the ground of the answers given by the patients to the single questions and on the grounds of the total score D (= depression index) and relating the previous data with the clinical-functional ones. Finally we have compareted these data with those ones connected with non selected population. So we have succeeded in outlining a psychophysical profile of the patient suffering from chronic respiratory diseases. Such a profile is marked by an objective element, that is pathology, and by a psychological element inserted into the organic one as there is an inter-dependence between pathology and psychological features. From the collected data, we have noted the behavioural spheres which are more upset are working capacities, sleep and mood and these features are directly proportional to the seriousness of the pathology. From a practical and therapeutic point of view, all this can be of great importance. PMID- 1306635 TI - [Aerosol thymopentin in the prevention of relapse of chronic bronchitis]. AB - In this study the Authors have verified the efficacy of Thymopentin administered via aerosol in the prevention of recurrent catarrhal episodes in the patients affected by COPD during the winter season, compared to the previous winter. In October, 1 phial of Thymopentin was administered via aerosol to 15 patients affected by COPD, daily, for 10 consecutive days; all patients were evaluated at monthly clinical control for 4 months and all patients were invited to keep a diary of daily variations. After 4 months from treatment a net improvement was observed in the clinical parameters studied: sputum (volume and purulence), cough and dyspnoea, but the most interesting datum was the total absence of recurrent episodes of infection, associated to the reduction in quantity of antibiotics, mucolytics and number of days of illness and with noticeable improvement in the quality of life of the patients. PMID- 1306636 TI - [Changes in spirometric values induced by nasally administered beclomethasone dipropionate in patients with perennial allergic rhinitis]. AB - Authors showed that it's possible to control the asthmatic component in patients with persistent allergical rhinitis without bronchodilatory drugs. AA. compared two groups of ten patients: Group A has been treated with antihystaminical drugs or ketotifen per os and Disodium chromoglycate per nasal spray, Group B has been treated with the same drugs and Beclomethasone Dipropionate per nasal spray more (400 mcg a day). Respiratory functionality tests (FEV1 and MEF75) have been carried out at the beginning and at the end of the trial and the subsequent clinical parameters have been considered: dispnoea attacks, rhinorrhaea, sneezes, lost working or school days. The results of the study showed after three months of therapy a statistically significant improvement of FEV1 and MEF75 in Group B only; moreover the patients of the Group B had lower number of asthmatic attacks then patients of the Group A. PMID- 1306637 TI - [Multiple carcinomas: considerations on several cases with synchronous/metachronous involvement of the respiratory tract]. AB - The authors report their observations on 7 cases of multiple malignant tumors during the period 1988/1992 (frequency of 0.03 x 100). They report that primary malignant tumors involved the laryinx and the wang, and both the lungs in a synchronous or metacronous way. They suggest that pathogenesis of multiple malignant tumors may be very similar to that of multiple endocrinous neoplasms. PMID- 1306638 TI - Gouty arthritis following gunshot wound: a case report. PMID- 1306639 TI - Microvascular pressure profile of serosal vessels of rat trachea. AB - The distribution of intravascular pressures within the pulmonary airway microcirculation is an important determinant of transvascular liquid balance. Intravascular pressures were measured in the serosal vessels of the trachea in anesthetized, ventilated rats. The ventral portion of the trachea was surgically exposed and suffused with warm (37 degrees C) Krebs-Ringer bicarbonate. The serosal microvasculature was observed with a video microscope, and microvessel pressures and diameters were measured using the servo-null technique and video calipers, respectively. Mean arterial pressure (MAP) was monitored from the left femoral artery and averaged 106.1 +/- 5.2 mmHg (n = 14). The highest pressure (77% of MAP) was measured in a large (95-microns diam) transverse arteriole. As arteriolar diameter decreased from 39 to 11 microns, pressures fell from 62 to 18% of MAP. Capillaries drained into venular networks that formed extensive arcades. Pressures in these postcapillary venules (20-75 microns diam) were 7.7 +/- 5.5% of MAP (n = 9). These vessels in turn drained into large venous sinuses (120-425 microns diam) where pressures averaged 5.7 +/- 2.3% of MAP (n = 7). A four-parameter logistical model of these data predicts that capillary pressures range from 27 to 15% of MAP. We conclude that 1) a substantial resistance exists across precapillary arterioles less than 40 microns diam and 2) a small pressure drop occurs between systemic arteries and primary feed arterioles in this tissue. PMID- 1306640 TI - Assessing physicians' estimates of the probability of coronary artery disease: the influence of patient characteristics. AB - The authors assessed physicians' probability estimates of coronary artery disease (CAD) in 250 patients undergoing a screening exercise stress test. True likelihood of disease (prevalence) was derived from the literature. Discrimination and calibration were assessed by comparing physicians' probability estimates and prevalence using pairwise comparisons, rank correlation, and linear regression. There were differences in the discriminative abilities of the physicians based on patient characteristics. For example, the physicians had better discriminative ability for patients with typical cardiac chest pain compared with atypical chest pain. The physicians were able to predict the prevalence of CAD in broad groups of patients. However, they overestimated probabilities for patients with low prevalence of disease and underestimated probabilities for patients with high prevalence of disease. The authors conclude that physicians make consistent errors in the use of probability estimates. The quality of these estimates depends on patient characteristics such as type of chest pain and true likelihood of disease. PMID- 1306641 TI - Spatial delirium following a right subcortical infarct with frontal deactivation. PMID- 1306642 TI - Acute management of the burned patient. PMID- 1306643 TI - Infant acceptance of postexercise breast milk. AB - The purpose of this study was to observe the infant acceptance of postexercise breast milk. Twenty-six lactating postpartum women exercised to maximum (maximum oxygen consumption = 35.1 +/- 9.2 [SD] mL min-1 kg-1) on a treadmill. Breast milk was collected via self-expression at rest before exercise and at 10 and 30 minutes postexercise and analyzed for lactic acid by enzymatic methods. Following exercise, infants were presented with their mothers' pre-exercise and postexercise milk in a double-blind design. The mother rated the infant's acceptance of the milk samples. There was a significant difference in acceptance of pre-exercise and postexercise milk as analyzed by analysis of variance. Maximal exercise resulted in a significant increase in lactic acid concentration in breast milk that may be high enough to affect the taste of the milk. The decreased acceptance of postexercise milk was associated with increased lactic acid concentration. Suggestions to circumvent the decreased acceptance are offered. PMID- 1306644 TI - Time trends in gastric carcinoma: changing patterns of type and location. AB - To determine whether there have been major changes in various aspects of gastric carcinoma, we reviewed the records of 302 patients with gastric cancer diagnosed between 1973 and 1989. Patients were divided into two groups: group I, 1973-80 (n = 163), and group II, 1981-88 (n = 139). On admission, no significant differences in presenting symptoms and physical signs were found, except for an increase in dysphagia (p less than 0.005) in group II. Endoscopy with targeted biopsy and biphasic-contrast examination were of equal merit in detecting malignancy (99.7%). A significant increase in the proportion of patients with cardia carcinoma was noted in group II (p less than 0.02). The proportion of patients with early gastric cancer decreased from 11% to 7.2%. The proportion of patients with intestinal-type carcinoma decreased in period II (p less than 0.05), accompanied by an increase in the proportion of patients with diffuse-type carcinoma during the same period (p less than 0.01). The overall 5-yr survival estimate was 17%. Independent prognostic variables were T stage (p less than 0.0001) and N stage (p less than 0.001), whereas Lauren type and tumor site were only significant in univariate survival analysis (p less than 0.05 and p less than 0.005, respectively). PMID- 1306645 TI - A simple and safe technique of left ventricular venting. AB - Left ventricular venting has many physiologic and practical benefits. A venting technique is described that employs a simple, closed system which allows the perfusionist to monitor left ventricular distention. By monitoring the left ventricular volume the perfusionist can regulate the degree of negative pressure on the vent and thus reduce the chance of air entering the heart. PMID- 1306646 TI - High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. AB - We conducted a multicenter controlled trial to test the hypothesis that high-dose intravenous immune globulin (HDivIG) therapy can modulate bilirubin production and reduce the frequency of exchange transfusions in newborn infants with Rh hemolytic disease. Thirty-four patients with Rh incompatibility proved by positive direct antiglobulin test (Coombs test) results were randomly assigned to receive conventional treatment including phototherapy, with or without additional HDivIG therapy at 500 mg/kg given for a 2-hour period as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded the modified curves of Polacek by more than 2 mg/dl. Two patients were excluded because of protocol violations. The results in 32 infants were analyzed. In the HDivIG group, 2 (12.5%) of 16 children required exchange transfusions, whereas it became necessary in 11 (69%) of 16 children in the control group (p less than 0.005). Bilirubin levels in the HDivIG group were lower despite reduced frequency of exchange transfusions. No side effects of HDivIG treatment were observed. We conclude that HDivIG therapy by a yet unknown mechanism reduces serum bilirubin levels and the need for blood exchange transfusions in children with Rh hemolytic disease. PMID- 1306647 TI - Does the type of anomalous arrangement of pancreaticobiliary ducts influence the surgery and prognosis of choledochal cyst? AB - A new classification of the anomalous arrangement of pancreaticobiliary ducts (APBD) has been proposed following amendments and modificiations of the previous one. Fifty-one cases of choledochal cyst complicated with APBD were extensively examined and analyzed for clear visualization of the APBD system to make a standard classification. APBD were classified broadly into three types: type I, type II, and type III with their subtypes. Type I of APBD was seen in 18 (35.3%), type II in 11 (21.6%) and type III in 22 (43.1%) cases, respectively. A radical operation, including complete excision of the dilated biliary duct followed by reconstruction of the biliary tract was the surgical treatment of choice, because the reflux of the pancreatic juice into the biliary tract is prevented. However, a dilated common channel or accessory pancreatic duct, according to the new Komi type Ib, IIb, and IIIc3 of APBD, could be the cause of relapsing pancreatitis leading to chronic pancreatitis, due to the formation of a protein plug or pancreatic calculus in the dilated duct, even after this radical operation. In two complicated cases of type IIIc3 of APBD in choledochal cyst, we performed a pylorus-preserving pancreatoduodenectomy as one of the operative methods of choice. Long-term follow-up, more than decades, is essential to evaluate the results of surgical procedure for choledochal cyst, especially in those complicated cases with type Ib, IIb, and IIIc3 of APBD according to the new Komi's classification. PMID- 1306648 TI - Minnesota's HealthRight not necessarily a disaster. PMID- 1306649 TI - Storage and transfusion of platelets collected by an automated two-stage apheresis procedure. AB - Platelets collected by using a two-stage automated blood cell separator were evaluated after 5 days of storage. The procedure caused no unanticipated physiologic changes in donors and produced greater than 3 x 10(11) intact platelets in 200 mL of plasma, plus an additional 400 mL of plasma with intact coagulation factors. Posttransfusion recovery of autologous radiolabeled platelets was comparable to that seen in platelets prepared by manual centrifugation techniques. Corrected count increments in 14 patients showed results similar to those with control transfusions. This device, which involves a collection time of less than 90 minutes, provides an option for platelet-pheresis in a variety of settings including blood mobiles. PMID- 1306651 TI - Intraosseous infusion: elective use in pediatric anesthesia. PMID- 1306650 TI - Effect of one hour of passive cigarette smoking on lung function and airway responsiveness in adults and children with asthma. AB - We exposed 18 adults with bronchial asthma, 16 healthy controls and 11 children with asthma for 1 h either to ambient air (AA) or to environmental tobacco smoke (ETS). Exposure was performed at rest in an exposure chamber. Before and after exposure symptom scores and lung function were determined. After exposure bronchoprovocation tests with methacholine (adults) or histamine (children) were performed to determine the concentrations causing a 100% increase in SRaw (PC100SRaw), and a 20% fall in FEV1 (PC20FEV1). In adult asthmatics mean (SD) SRaw before and after Sham was 8.8 (3.6) and 8.4 (3.6) cmH2O.s, and mean FEV1 (SD) was 3.18 (0.97) and 3.14 (0.9) 1, respectively. Before and after passive smoking mean SRaw (SD) was 7.5 (3.0) and 7.2 (2.7) cmH2O.s, and mean FEV1 (SD) was 3.31 (1.0) and 3.21 (0.88) 1, respectively. Geometric mean (SD) PC100SRaw and PC20FEV1 after Sham were 0.38 (4.5) and 0.29 (4.1) mg/ml, after passive smoking 0.39 (5.1) and 0.36 (4.7) mg/ml, respectively. In healthy controls there was no consistent effect on the respective parameters during exposure. In children mean (SD) SRaw before and after Sham was 8.7 (3.6) and 9.0 (3.2) cmH2O.s, and mean FEV1 (SD) was 1.97 (0.32) and 1.98 (0.40) 1, respectively. Before and after passive smoking mean SRaw (SD) was 10.4 (5.3) and 9.4 (3.3) cmH2O.s, and mean FEV1 (SD) was 1.95 (0.37) and 1.94 (0.35) 1, respectively. Geometric mean (SD) PC100SRaw and PC20FEV1 after Sham were 1.39 (3.0) and 0.70 (2.7) mg/ml, and after passive smoking 1.65 (2.5) and 0.96 (2.3) mg/ml, respectively. There were no significant differences in lung function and airway responsiveness between exposure to ambient air or ETS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306652 TI - Subtotal splenectomy in Gaucher's disease: towards a definition of critical splenic mass. AB - Partial splenectomy is currently the favoured surgical approach for Gaucher's disease. Preservation of splenic tissue is indicated to prevent susceptibility to overwhelming postsplenectomy sepsis, to delay the massive deposition of glucocerebroside in the liver and bones, and to relieve symptoms of hypersplenism. Controversial issues and technical problems related to partial splenectomy for Gaucher's disease are discussed and a definition of critical splenic mass considered. PMID- 1306653 TI - Functional imaging of peripheral vascular disease: a comparison between exercise whole-body thallium perfusion imaging and contrast arteriography. AB - Whole-body thallium scintigraphy was used to study leg muscle perfusion in 12 healthy individuals and 31 patients with peripheral vascular disease. Subjects were scanned immediately after exercise and 4 hr later. Buttock, thigh and calf perfusion were measured in terms of fractional uptake relative to whole-body activity, percent change in fractional uptake over 4 hr and interextremity symmetry ratios. The results were compared to contrast arteriography on a region by region basis. The overall sensitivity and specificity of thallium scintigraphy were 80% and 73%, respectively. The results suggest that thallium scintigraphy may provide useful information about the hemodynamic significance of noncritical anatomic lesions. PMID- 1306654 TI - Health care reform--where are we and where should we be going? PMID- 1306655 TI - Introducing products to prevent needlesticks. PMID- 1306656 TI - What proportion of isotope injected does the child receive in dynamic renal scanning? AB - Because of significant difficulties encountered in the manipulation of data from 99Tcm-DTPA and 99Tcm-mercaptoacetyltriglycine (MAG3) renogram studies, it was decided to try to improve the percentage dose of radioisotope injected and thus the number of counts obtained by using a minimum dose volume of 1 ml for all injections. This resulted in an improvement in the percentage dose injected. However, difficulties were still encountered in the younger children. 18.7% of children aged less than 3 months, received less than 50% of the injected dose, showing little or no improvement using the newer method. The difficulty of injecting small babies seems the most obvious reason. During the interpretation of the findings in paediatric radioisotope studies, it is important to remember that not all children may have received an adequate percentage dose to constitute a reliably diagnostic study. PMID- 1306657 TI - Catatonia on the consultation-liaison service. AB - Catatonia is a syndrome that requires both nonpsychiatric medical and psychiatric evaluation. The authors report on six patients with catatonia that were seen by a psychiatric consultation-liaison service. Five of these patients had medical conditions reported to cause catatonia. Treatment recommendations included the following: 1) subcutaneous heparin for deep venous thrombosis prophylaxis, 2) a trial of lorazepam, and 3) transfer to a medical/psychiatric unit or locked psychiatric unit. Catatonia was most parsimoniously attributed to the primary psychiatric illness in five of the patients and to corticosteroid treatment in the sixth patient. These findings suggest that clinicians should use the proposed criteria, past psychiatric history, physical exam, and laboratory and radiological studies when evaluating patients with symptoms of catatonia. PMID- 1306658 TI - Does folate supplementation make sense in patients with rheumatoid arthritis treated with methotrexate? PMID- 1306659 TI - Carbamazepine and episodic dyscontrol. PMID- 1306660 TI - Quality of life following surgery for abdominal aortic aneurysm. AB - Repair of abdominal aortic aneurysm (AAA) carries a considerable rate of morbidity and mortality, but little information exists on the quality of life following this procedure. During 1988 and 1989, in two hospitals, 211 patients (186 men and 25 women; median age 74 (range 48-87) years) underwent surgery for AAA. There were 77 ruptured aneurysms and 134 electively repaired. Of these, 38 patients died in hospital (27 ruptured, 11 elective); by the time of review a further eight (one ruptured, seven elective) had died from unrelated causes. Of the 165 survivors, 131 (45 ruptured, 86 elective) were reviewed and questioned as to their physical and mental state before and after surgery. Using the Rosser index, a value for quality of life before and after surgery was calculated (1.0, good; 0, dead). The value for the elective group was 0.94 before operation and 0.96 after, but in the ruptured group fell from 0.98 before surgery to 0.87 afterwards. This study shows that patients undergoing elective surgery for repair of AAA retain good quality of life. By contrast, patients surviving emergency surgery following this procedure seem to suffer a deterioration in life quality, which must be endured for the same expected lifetime as that for the elective group. These results support the need for a national AAA ultrasonographic screening programme. PMID- 1306661 TI - Information technologies in US medical schools. Clinical practices outpace academic applications. PMID- 1306662 TI - Childhood immunizations. PMID- 1306664 TI - Use of the Palmaz stent in ostial celiac artery stenosis. AB - The author reports a case in which a 20-mm balloon-expandable Palmaz stent was used with percutaneous transluminal angioplasty to treat a stenosis of the proximal celiac artery in a patient with mesenteric ischemia. The stent was dilated to 9 mm, eliminating the stenosis. The patient made an uneventful recovery and remains asymptomatic at 4 months. PMID- 1306663 TI - Outcome of White pump shunt surgery for neovascular glaucoma in Asians. AB - We compared the effect of seton (White pump shunt) surgery (16 eyes) with that of trabeculectomy and 5-fluorouracil (31 eyes) in treating 38 Asian patients with medically uncontrollable neovascular glaucoma. We found the probability of long term success (intraocular pressure < or = 26 > or = 5 mm Hg) of seton surgery (53.0% at 3 years) to be similar to that obtained following trabeculectomy with adjunctive 5-fluorouracil (45.4% at 3 years). However, 3 years postoperatively, the probability of the preservation of visual acuity was significantly greater following trabeculectomy than seton surgery (67.1% vs 23.1%; P < .05). In addition, the prevalence of postoperative complications was higher with the seton procedure (P < .001). The loss of endothelial cells 6 months postoperatively was more marked with seton surgery than with trabeculectomy, whether the shunt device touched the cornea (P < .000001) or not (P < .0005). In conclusion, White's pump shunt was effective in lowering the IOP of eyes with neovascular glaucoma. However, care must be taken to prevent postoperative complications, the incidence of which exceeded those observed following trabeculectomy with adjunctive 5 fluorouracil. PMID- 1306665 TI - Indomethacin treatment in children with daytime frequency of micturition. AB - Thirty children with daytime urinary frequency (DUFC) were randomly divided into two groups. The first group was given oral indomethacin, 1 mg/kg per dose, three times a day for 7 days. The frequency of urination fell from 26.3 +/- 2.3 to 11.7 +/- 2.8 at the end of the treatment period. The second group was treated with oral chloramphenicol, 30 mg/kg per day, in four divided doses for 7 days. Their urinary frequency did not change. They were then treated with a 1-week course of indomethacin and responded in a similar manner to group 1 patients. The use of indomethacin was accompanied by significant increases in plasma carbon dioxide combining power, urine osmolality and urine pH; urine sodium and potassium levels decreased. These results show that a short course of indomethacin, in low dose, improves DUFC. We propose that it acts by inhibiting prostaglandin synthesis which modifies tubular function and increases urinary pH. PMID- 1306666 TI - The value of water-soluble contrast radiology in the management of acute small bowel obstruction. AB - A series of 127 consecutive patients with symptoms and signs and radiological features suggestive of acute small bowel obstruction underwent water-soluble contrast small bowel follow-through examination. A dose of 100 ml of Gastrograffin in adults, or 20-50 ml in children, was injected via a nasogastric tube and supine plain abdominal radiographs were taken at 30 min and 4 h after administration. If contrast passed to the colon a non-operative course was followed. If there was a clear cut-off in contrast level in the small bowel or if contrast failed to pass into the large bowel by 4 h, patients underwent laparotomy. Based on these radiological findings 15 patients (11.8%) underwent surgery and all had established small bowel obstruction at laparotomy. The remaining 112 patients were successfully managed conservatively. Water-soluble contrast radiology is safe, easy to use and to interpret, and is a major benefit in differentiating mechanical from other causes of small bowel obstruction. Our experience indicates that this underused technique is of significant value in identifying those patients who require urgent surgery. PMID- 1306667 TI - Prevention of malalignment during non-reversed femorodistal bypass. AB - A simple technique is described using a Doppler flowmeter to prevent malalignment of a vein graft during femorodistal reconstruction. In 63 non-reversed vein bypass grafts, this technique has been used and no evidence of malalignment has been found on subsequent completion arteriography. PMID- 1306668 TI - Fluoxetine and suicidal behaviour. Some clinical and theoretical aspects of a controversy. PMID- 1306669 TI - Immunization against typhoid fever. PMID- 1306670 TI - Kwashiorkor and marasmus: evolution and distinguishing features. 1968. PMID- 1306671 TI - The search for a superior toothbrush design technology. PMID- 1306672 TI - Comparative plaque removal efficacy of three toothbrushes in two independent clinical studies. AB - Two independent studies were conducted to evaluate and compare the clinical performance of three toothbrushes on plaque removal. Both studies were carried out under the same protocol. A total of 73 adult male and female subjects who met the inclusion/exclusion criteria completed Study I and 78 different subjects completed Study II. Subjects were initially screened for dental plaque eligibility. After plaque was scored on the facial and lingual surfaces of all natural teeth using the Rustogi, et al. index, qualifying subjects were randomly assigned to one of three groups on the basis of initial plaque scores and number of teeth. Subjects were then dismissed and scheduled to return for Visit 1 a week later, having abstained from all oral hygiene procedures for a prior 24-hour period. At Visit 1, each group was evaluated for plaque before brushing with their assigned toothbrush for sixty seconds. They were again scored for plaque after brushing. Subjects were dismissed and instructed to resume their normal routine and return to the clinical site for two more weekly visits. At each visit, a different test toothbrush was assigned to each group in a cross-over design. Plaque evaluations and brushing procedures were performed as in Visit 1 of the study. In both studies, the Colgate Precision toothbrush was significantly more effective (p < 0.01) than both the Oral-B 40 and Reach Full-Head soft toothbrushes in reducing the whole mouth plaque scores, as well as plaque at the gumline and at interproximal areas. The Oral-B 40 and Reach toothbrushes were not significantly different from each other with regard to plaque removal. PMID- 1306673 TI - Clinical studies regarding the plaque removal efficacy of manual toothbrushes. AB - Two independent cross-over design studies were performed to compare two toothbrushes for their ability to remove plaque. In Study I, the Colgate Precision toothbrush was compared to the Oral-B 40 toothbrush; in Study II, the Colgate Precision toothbrush was compared to the Reach Full-Head soft toothbrush. A total of 54 and 72 adult male and female subjects who met the inclusion/exclusion criteria completed Study I and Study II, respectively. In each study, subjects refrained from brushing for 24 hours, and were screened for dental plaque on the facial and lingual surfaces of all natural teeth, using the Rustogi, et al. index. Based on mean scores and number of teeth, qualifying subjects were randomly assigned to one of two groups. Subjects were then scheduled to return one week later, having again abstained from all oral hygiene procedures for a 24-hour period. At this visit, each subject was evaluated for plaque, then brushed with his/her assigned toothbrush for sixty seconds, and was again scored for plaque after brushing. Subjects were instructed to resume their normal routine and return to the clinical site one week later. At this visit, a different test toothbrush was assigned to each group in a cross-over design. Plaque evaluations and toothbrushing procedures were again performed. In both studies, the Colgate Precision toothbrush was significantly more effective (p < 0.01) than either the Oral-B 40 toothbrush or the Reach Full-Head soft toothbrush in reducing whole mouth plaque scores, plaque scores at the gumline, and plaque scores at interproximal areas. PMID- 1306674 TI - The toothbrush--a new dimension in design, engineering, and clinical evaluation. PMID- 1306675 TI - Comparative laboratory evaluation of three toothbrushes regarding interproximal access efficacy. AB - A new toothbrush from the Colgate-Palmolive Company, called the Colgate Precision toothbrush, was compared to the Oral-B 40 toothbrush and Reach Full-Head soft toothbrush using a laboratory device designed to simulate clinical toothbrushing motions and pressures. The toothbrushing time was sixty seconds for each vertical or horizontal brushing motion and for each of the three brushing weights tested, 250, 500 or 750 grams. Interproximal access efficacy was determined by measuring the maximum width of the brushing stroke measured on pressure sensitive paper placed around the simulated anterior or posterior teeth. Twenty-four toothbrushes of each design were evaluated for each toothbrushing motion, tooth shape and toothbrushing weight for a total of 864 measurements. In all studies conducted, the Colgate Precision toothbrush had statistically superior total interproximal access efficacy scores compared to the Oral-B and Reach toothbrushes. In several assessments the Reach toothbrush was superior to the Oral-B 40 toothbrush. PMID- 1306676 TI - Refinement of the Modified Navy Plaque Index to increase plaque scoring efficiency in gumline and interproximal tooth areas. AB - To improve the assessment of plaque present on teeth, a new index, based on the original Modified Navy Plaque Index, has been developed. The primary modifications to the original Modified Navy Plaque Index were: (1) extending areas F (distal) and D (mesial) into the region just below the interproximal contact point, and (2) extending areas C and A so as to increase the gumline (or marginal gingiva) region. The new index assesses the amount of plaque in the tooth area bounded by the tooth contact, the free gingival margin, and mesial or distal line angles. The use of this new index enables the examiner to evaluate and record both the gumline (or marginal areas) and interproximal areas of the tooth, thus giving these an anatomical areas an increased importance. A pilot clinical assessment study was conducted to utilize this new index in evaluating the plaque removal efficacy of five manual toothbrushes. The results from this pilot study indicated that, when the new plaque scoring index was used, significant differences between pre-toothbrushing and post-toothbrushing plaque scores (as well as among toothbrush groups) could be demonstrated. Further, these differences (plaque removal efficacy) were demonstrated on an interproximal (mesial and distal) basis and a gumline (or gingival margin) basis, as well as on a whole mouth basis. PMID- 1306677 TI - Thirty-day evaluation of the Stimu-gum gingival stimulator and tooth polisher for clinical safety and efficacy. AB - Two clinical studies have been performed to assess the intraoral safety and efficacy of a mechanical device containing a rubber cup polisher and interdental stimulator (Stimu-gum). In the first study the potential for producing irritation of the oral mucosal tissues was evaluated in 19 subjects when the Stimu-gum product was used in an exaggerated manner, i.e., five times a day for seven days. No untoward effects attributed to use of the Stimu-gum product were observed or reported at anytime in the study. A thirty-day study on 64 subjects compared the Stimu-gum device with an Oral-B 35 manual toothbrush for safety, plaque removal and gingivitis evaluations, at baseline and after 15 and 30 days of product use. The Stimu-gum product and the Oral-B toothbrush were equally effective in removing overnight plaque. The Stimu-gum device was significantly more effective than the Oral-B toothbrush in reducing gingivitis scores at 30 days and bleeding on probing at 15 days. Bleeding on probing scores continued to be lower in the Stimu-gum group at 30 days; however, differences were not statistically significant compared to the Oral-B mean scores. PMID- 1306678 TI - Effect of fluoridated milk on caries: 10-year results. AB - The aim of the study was to assess the caries-preventive effect of fluoridated milk after 10 years of consumption, including a two-year interruption. DMF mean values of 162 institutionalized children aged 7- to 14-years were compared to DMF mean values of 139 institutionalized children (control) of the same age. The test group children consumed 200 ml milk daily, implemented with 0.4 mg-to 0.75 mg F, depending on their age, continuously for six years. Following a two year interruption, the children again got fluoridated milk or cocoa-milk twice a week for four years. In the test group the average ratio of caries-free children was 10% more than in the control group. The caries prevalence in the permanent dentition showed a clinically and statistically significant reduction: 36.78% on DMFT, and 40.02% on DMFS mean values. PMID- 1306679 TI - The clinical effect of a dentifrice containing triclosan and a copolymer in a sodium fluoride/silica base on plaque formation and gingivitis: a six-month clinical study. AB - A six-month, double-blind clinical study was entered into by three hundred twenty five (325) male and female adult subjects to assess the efficacy of a dentifrice containing 0.3% triclosan (Irgacare MP, Ciba-Geigy Corp.) and 2.0% of a copolymer of methoxyethylene and maleic acid (Gantrez, ISP Corp.) on supragingival plaque formation and gingivitis, compared to a placebo dentifrice over a six-month period. Each dentifrice, the triclosan and the placebo, contained 0.243% sodium fluoride in a silica base. Only those subjects who were free of periodontal disease (no pockets > 4 mm), demonstrated a level of at least mild gingivitis (modified Loe-Silness score > or = 1.0) and had a modified Quigley-Hein Plaque Index score of > or = 1.5 were admitted into the study. Baseline plaque and gingivitis scores were used to stratify the subjects into two balanced groups. A thorough oral prophylaxis was administered to all subjects. They were then assigned either the triclosan/copolymer dentifrice or the placebo dentifrice to use for the next six months. Evaluation for gingivitis and supragingival plaque formation was made after three and six months. Evaluations made after six (6) months demonstrated a 17.0% statistically significant (at the 99% level of confidence) reduction in supragingival plaque formation was provided by the triclosan/copolymer dentifrice, compared to the placebo dentifrice. An 18.6% statistically significant (at the 99% level of confidence) reduction in plaque formation on the tooth surfaces with the highest plaque formation was provided by the triclosan/copolymer dentifrice, compared to the placebo dentifrice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306680 TI - Characterization of volatile sulphur compounds production at individual gingival crevicular sites in humans. AB - The present investigation describes a method for collection and analysis of volatile sulphur compounds (VSC) from gingival crevicular sites in humans. Tenax GC trapping devices were used to adsorb and concentrate VSC from crevicular air at -55 degrees C, which were then thermally desorbed at 120 degrees C. Gas chromatographic (GC) analyses were performed using a Tracor 550 GC equipped with a flame-photometric detector and a Teflon column packed with 5% polyphenyl ether and 0.05% phosphoric acid on 30-40 mesh Teflon. Sulfides identified from crevicular sites include hydrogen sulfide [H2S], methyl mercaptan [CH3SH], dimethyl sulfide [(CH3)2S], and dimethyl disulfide [(CH3S)2]. Of the seventeen patients studied, crevicular sites that were either deep (P.D. > or = 4 mm) or inflamed (BoP = 1) exhibited significantly larger CH3SH to H2S ratios than corresponding crevicular shallow (P.D. < or = 3 mm) sites (p < .10) or noninflamed (BoP = 0) sites (p < .05). Similarly, total sulphur in deep and inflamed sites was significantly higher than in corresponding shallow (p < .01) and noninflamed (p < .05) sites. This is the first known in vivo study to quantitate VSC directly from individual gingival crevices. PMID- 1306681 TI - The interleukin network and lymphoid development. AB - Lymphoid development differs sharply between the primary and secondary lymphoid organs. In the former, lymphocytes arise from precursors by antigen-independent processes under thymic or bone marrow microenvironmental influences and undergo extensive selective processes before being allowed to leave. In the latter, lymphocytes with receptors relevant to particular antigens undergo a second wave of proliferation and differentiation leading to the emergence of immunocytes with effector functions. Each of the two sets of events are profoundly dependent on cellular interactions. In the primary lymphoid organs, the "action" centres on stromal cell-lymphoid precursor interactions, and artificial systems permitting B cell formation are much more advanced than those for T cell development. For B cells, IL-7 and c-kit ligand (KL) are clearly important but so are as yet undefined stromal cell-derived activities. For thymic development, only fragments of the complex 3-week process of T cell formation can be mimicked in vitro and no IL has unequivocally been shown to be critical. Within the secondary lymphoid organs, where lymphocytes react to the antigenic universe, the key to regulation lies in interactions between accessory cells (dendritic cells, macrophages and their various relatives) T cells and B cells. Efforts to squeeze the relevant cytokines into sharp compartments such as activation factors, growth factors and differentiation factors have been largely unsuccessful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306682 TI - The alternative-splice isoforms of the PDGF A-chain differ in their ability to associate with the extracellular matrix and to bind heparin in vitro. AB - Platelet-derived growth factor (PDGF) consists of disulfide-linked homo- or heterodimers of A and B chains. mRNA encoding the A chain (PDGF-A) occurs in two versions that differ by the presence or absence of a single short exon. These alternatively-spliced mRNAs encode polypeptides that differ in length by fifteen amino acids. The longer isoform (PDGF-AL) possesses a highly basic carboxy terminal extension that is responsible for retaining PDGF-AL homodomers at the cell surface after secretion, while homodimers of the shorter isoform (PDGF-AS) are released into the extracellular medium. We have investigated the mechanism by which PDGF-AL remains in association with the cells that produce it. We expressed epitope-tagged versions of PDGF-AL and PDGF-AS in Cos cells and compared their intra- and extracellular distributions by immunofluorescence microscopy. PDGF-AL, but not PDGF-AS, was detected on and around cells in a diffuse pattern suggesting associated with the extracellular matrix (ECM). Metabolically radiolabelled PDGF AL, but not PDGF-AS, could be eluted from ECM preparations by washing in high salt. Moreover, PDGF-AL bound reversibly to heparin-Sepharose in vitro at physiological salt concentrations, eluting at a salt concentration around 0.5 M. PDGF-AS did not bind to heparin under the same conditions. Thus, PDGF dimers that contain PDGF-AL may remain immobilized near the cells that secrete them by virtue of binding to heparin-like constituents of the ECM. PMID- 1306683 TI - Recombinant PDGF from lower vertebrates: receptor binding and immunochemical analysis with metabolically labeled growth factor. AB - We used a baculovirus vector/insect host cell system to express cDNA clones of PDGF A genes from mouse and frog (Xenopus laevis). The insect host cells process PDGF A subunits from either frogs or mice into biologically active AA homodimers with yields in the range of 0.5-1.0 mg/liter of culture medium. The recombinant PDGFs can be metabolically labeled with 35S-cysteine for use in radioreceptor and radioimmunoassays. Neutralizing polyclonal antisera can be raised against the mouse and frog PDGFs. These antisera are markedly species-specific in action. However, in radioreceptor binding assays and bioassays for mitogenic activity, human, mouse and frog PDGF AA homodimers occupy and activate murine PDGF receptors with equal efficiency. PMID- 1306684 TI - Interaction of heparin-binding EGF-like growth factor (HB-EGF) with the epidermal growth factor receptor: modulation by heparin, heparinase, or synthetic heparin binding HB-EGF fragments. AB - The binding of heparin-binding EGF-like growth factor (HB-EGF) to the epidermal growth factor (EGF) receptor of human endometrial carcinoma cells was compared to that of EGF using an 125I-EGF radioreceptor assay. The inhibitory effect of HB EGF on 125I-EGF binding was reversed either in the presence of heparin (but not by chondroitin sulfate) or by pre-treating the cells with heparinase. These treatments did not affect the binding of EGF to its receptor. To map potential regions in the HB-EGF molecule that mediate its heparin-dependent interaction with the EGF receptor, HB-EGF peptides were synthesized that were non-homologous to EGF. Accordingly residues 20-25 and 36-41, but not residues 8-19, of HB-EGF were found to be (i) heparin-binding and (ii) modulators of HB-EGF (but not of EGF) binding to the EGF receptor. PMID- 1306685 TI - Interleukin 2 and tumor necrosis factor alpha are complementary for proliferation of the hematopoietic stem cell line LyD9. AB - We have shown that tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL 2) are complementary for stimulation of growth of the hematopoietic stem cell line, LyD9. Neither TNF alpha nor IL-2 alone could stimulate the proliferation of LyD9 cells even after pre-incubation with these growth factors. The number of high-affinity IL-2 receptors on LyD9 cells did not increase after incubation with IL-2 and TNF alpha. These results suggest that the proliferative response of LyD9 by TNF alpha and IL-2 is not mediated by receptor inducing activities. We used the induction of the proto-oncogenes c-myc and c-pim to characterize the proliferative stimulation by IL-2 and TNF alpha. Northern blot analysis revealed that the simultaneous addition of IL-2 and TNF alpha was more efficient than IL-2 alone for c-myc mRNA induction. However, the addition of TNF alpha and IL-2 could not increase c-pim mRNA more than the level induced by IL-2 alone. The results indicate that the two growth factors complement each other by transducing different types of growth signal. PMID- 1306687 TI - Never ending growth and a growth factor. I. Immunocytochemical evidence for the presence of basic fibroblast growth factor in a tapeworm. AB - Basic fibroblast growth factor immunoreactivity (bFGF-IR) was detected in a specific set of nerve cells in the central nervous system of the gull-tapeworm Diphyllobothrium dendriticum (Cestoda)--an obligatory endoparasite. The long varicose processes of the bFGF-IR neurons extend along the two main nerve cords, which contain an actively growing population of nerve cells. A neurotrophic function for the bFGF-like material is proposed. The adult tapeworm lives in the intestine of a homeothermic host and has a pattern of very active and never ending growth. The larval stages live in poikilothermic hosts and grow very slowly. The bFGF-IR nerve cells occur both in II stage larvae and in adult worms. Thus, no correlation between the presence of bFGF-IR and the general growth rate of the worm was found. Western blot analysis revealed the presence of an anti bFGF immunoreactive peptide with a molecular mass of 47 kDa in both larval and adult worms. PMID- 1306686 TI - The interaction of amphiregulin with nuclei and putative nuclear localization sequence binding proteins. AB - Amphiregulin (AR) is a 23 kDa, bifunctional growth modulating glycoprotein belonging to the epidermal growth factor (EGF) family of polypeptide growth regulators. AR possesses two putative nuclear localization sequences (NLS), binds to DNA sepharose, and localizes to the nucleoli of human ovarian surface epithelial carcinoma cells suggesting that AR has a direct nuclear role. We have found that 125I-labeled AR, when exogenously applied to several carcinoma cell lines, associated with nuclei in a time, temperature, and concentration dependent fashion. The control peptide, EGF, also associated with these fractions but at approximately 20% of the efficiency of AR. Cross-linking experiments with 125I labeled AR and nuclear fractions derived from various carcinoma and normal cell lines demonstrated that AR binds two proteins of molecular mass 205 and 120 kDa. AR binding to these nuclear fraction proteins was specific and saturable as shown by competition experiments utilizing both SV-40 large T antigen NLS and an AR derived peptide encompassing both putative AR NLS. The combined results suggest that nuclear interactions may play a significant role in AR induced growth responses. PMID- 1306688 TI - The UNOS Scientific Renal Transplant Registry. AB - 1. One-year graft survival rates were 80%, 74%, and 66% for recipients of first (27,755), second (4,263), and multiple (914) cadaveric renal transplants, respectively. The 1-year patient survival rate was 94% for recipients of first or second grafts and 92% for multiply retransplanted patients. Half-lives projected for all cadaver transplants surviving the first year were approximately 8 years. 2. One-year graft survival rates were 95% for recipients of HLA-identical sibling donor transplants (1,493), 91%, 90%, and 89% for recipients of 1-haplotype matched sibling (1,787), parent (2,118), and offspring (715) donor grafts, respectively. One-year patient survival was 94% for parents receiving transplants from their children and 98% for all other recipients of kidneys from immediate family members. Projected half-lives were 26 years for HLA-identical grafts and 12-14 years for 1-haplotype-mismatched transplants from living related donors. 3. There were 181 transplants between spouses, with a 1-year graft survival rate of 92% and 99% patient survival. There were also 369 transplants from distant relatives or unrelated living donors with a 1-year graft survival rate of 86% and 95% patient survival. Projected half-lives for these transplants were 13 years. 4. Rejection episodes that occurred during the initial transplant hospitalization were reported in 24% of first and 33% of retransplanted recipients (p < 0.001). Rejection-free patients had an 85% 1-year graft survival rate compared with 67% and 58% in recipients of first or regrafts after early rejection (p < 0.001). Rejection episodes were strongly associated with histoincompatibilities. Among HLA-identical sibling transplants, 6% had early rejection compared with 12% of HLA-A,B,DR-matched cadaver transplants, 25% of parent-donor transplants and 28% of HLA-DR-mismatched cadaveric transplants. 5. The serum creatinine level (SCr) reported at the time of discharge was predictive of graft survival in both the short and long term. Recipients of first cadaver transplants discharged with SCr below 1.6 mg/dl (8,960) had a 91% 1-year graft survival rate and a projected half life of 12 years, while those with SCr above 3.5 mg/dl had 49% 1-year graft survival and 5.3-year projected half-life (p < 0.001). Discharge SCr was significantly influenced by the recipient's weight, the donor's age, and the cold ischemia time.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306689 TI - Twenty-five years of Eurotransplant: a truly European collaboration. PMID- 1306691 TI - Heart transplantation: update. AB - Clinical application of heart transplantation goes beyond 25 years experience. The main indications for cardiac transplantation remain idiopathic cardiomyopathies and ischemic diseases. To obtain a suitable donor has become progressively more difficult due to the increase of transplants performed and the shortage of donors. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical cardiac support. PMID- 1306690 TI - Organ donation in the United States: 1988 through 1991. AB - 1. During 1988 through 1991, the total number of cadaveric donors increased by 11% and the number of living donors increased by 25%. 2. During 1991, at least 1 kidney per donor was recovered from 94% of cadaveric donors. Livers were recovered from 70% of cadaveric donors; hearts from 47%, pancreases from 24%, lungs from 8%, and heart-lung combinations from 1%. The percentage of cadaveric donors from whom multiple organs were recovered increased by 23% between 1988 and 1991. 3. During 1988 through 1991, the largest group of cadaveric donors was White, male, age 19-35, with blood group O. During 1991, the primary cause of cadaveric-donor death was cerebrovascular. The largest group of living donors was also White and age 19-35; however, most donors were female. 4. Between 1988 and 1991, the percentage of cadaveric donors age 50-64 increased by 36% (from 11% in 1988 to 15% in 1991) and the percentage of cadaveric donors 65 years old or older increased by 200% (from 1% to 3%). 5. The percentage of White cadaveric donors declined by 4% between 1988 and 1991, while the percentage of Black donors increased by 16%. The percentage of Hispanic donors increased by 25% and that of Asian donors increased by 29%. 6. Throughout 1988 to 1991, the percentage of cadaveric hearts transplanted locally increased by 18% (from 55% to 65%). Interregional cadaveric kidney sharing also increased by 70% (from almost 10% to 17%). Local cadaveric liver transplantation increased by 80% (from 25% to 45%), resulting in a smaller percentage of livers shared interregionally. Local transplantation of cadaveric lungs increased by 173% (from 15% to 41%), reducing the lung discard/research rate by 69%, from 42% to 13%. PMID- 1306692 TI - Heart transplantation at the Heart Center North Rhine-Westphalia. AB - Since 1989, 427 heart transplants were performed at our center, limited only by donor availability, not by moderating donor criteria. Therefore, an increasing number of possible recipients was bridged with mechanical circulatory support systems. Immunosuppression was based on double-drug therapy (CsA, Aza) without steroid maintenance if possible and without mono- or polyclonal antibody prophylaxis. Monitoring adult transplant patients was based on endomyocardial biopsies only during the first 12 months posttransplant. In the pediatric group, only noninvasive diagnostic procedures were performed. Our present 1- and 3-year survival rates for heart transplant patients are 85% and 78%, respectively. We believe that only centers performing approximately 1,000 routine open-heart surgery procedures per year should be allowed to perform heart transplantation, with a minimum of 25 procedures per year (5). Our goal is to start our heart-lung and lung transplant programs in the near future. Our research interests are mainly in the field of postoperative monitoring, induction of immune tolerance, and in establishing a method to determine an individual immunosuppression protocol for each patient (6). PMID- 1306693 TI - Lung transplantation at the University of Pittsburgh. AB - Lung transplantation appears to be a therapeutic alternative for selected patients with end-stage pulmonary vascular and/or parenchymal disease. The greatest impediment to transplantation remains the availability of donor organs. This has become more significant as additional transplant centers become operational. The primary cause of death has been infection, and this most frequently occurs in the early post-transplant period. Significant progress has been made in curbing the morbidity and mortality from bacterial pneumonia and CMV infection, and this is the primary reason for improved survival rates. If the recipient survives the initial hospital stay, the likelihood of survival at 5 years is approximately 80%. The primary long-term complication is obliterative bronchiolitis which is poorly understood and difficult to treat. Nevertheless, the improvement in survival provides impetus to refine and improve the procedure so that survival can reach that attained by recipients of other major organ allografts. PMID- 1306694 TI - Liver transplantation at the University of Nebraska Medical Center from 1985 to 1992. AB - Based on our 7 and one-half-year experience with liver transplantation at the University of Nebraska Medical Center: 1. Success and growth of the program has been, in part, the result of close interaction and support of the various specialists involved. 2. We have demonstrated that outstanding patient and graft survival rates can be obtained with cyclosporine/prednisone immunosuppression. 3. Few, if any, technical contraindications exist to liver transplantation. 4. Surgical advances have allowed allografts to be salvaged which would otherwise require replacement. 5. Routine donor-liver biopsy prior to implantation has reduced the rate of primary nonfunction. 6. New strategies to improve survival for patients with hepatitis-B-related liver disease and hepatic malignancies undergoing liver transplantation need to be developed. 7. The management of patients with fulminant hepatic failure is evolving and now includes innovative approaches such as the use of ECLS and auxiliary transplants. PMID- 1306695 TI - The Pitt-UNOS Liver Transplant Registry. AB - Since the establishment of the scientific LTR, the frequency of OLTX has been increasing. Between 1988 and 1991, the number of procedures performed on pediatric patients increased by 28.2%, and among adult patients OLTX increased 84.8%. During this same period, the number of transplant centers performing OLTX rose 62.5% for children, and 54.7% for adult recipients. In 1991 there was a larger proportion of recipients under 1 year of age than in previous years. The effect was to lower the median age at transplantation from over 2 to between 1 and 2. In pediatric recipients of initial transplantation in 1991, compared with earlier recipients, the functional status at time of liver transplantation was improved. Fewer children were in the ICU while awaiting transplantation, and more were able to wait at home. Multiorgan transplantations in pediatric patients remained relatively rare, but a larger portion of these procedures in 1991 than was seen previously included the small intestine. Biliary atresia remained the most common indication for liver transplantation among children, accounting for over 55% of all OLTX procedures in 1991. There was a significant change in the racial distribution among adult recipients. Compared with previous years, there were greater proportions of Hispanic and Asian recipients in 1991. Adult recipients were older in 1991 than previously, and the median age increased from 46 to 49. As with pediatric recipients, adult recipients had better functional status in 1991 than earlier recipients. The increase in positive CMV serology was likely to be a function of older age. Among multiorgan recipients, the combination of liver and pancreas only was much less common in 1991 than previously. As was found previously (1), alcoholic cirrhosis continued to be the most common reason for OLTX, with the proportion of patients diagnosed with this condition increasing in 1991. Twice as many patients with cystic fibrosis were recipients in 1991 as in the prior 3 years. There were decreases in the proportion of patients receiving OLTX due to fulminant liver failure, metabolic disease, and malignant neoplasms. The cumulative probability of surviving (without retransplantation) 4 years after initial transplantation was 0.74 (0.61) for pediatric recipients. Univariate (unadjusted) analyses detected significant differences in survival for age (the youngest recipients had the worst survival), UNOS description (poorer functional status just prior to transplantation led to poorer survival), and primary liver disease (survival was worst for recipients transplanted due to fulminant liver failure, and best for patients with alpha-1 antitrypsin deficiency).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306697 TI - Combined kidney/pancreas transplantation at the Ohio State University Hospitals. AB - We conclude that combined kidney and pancreas transplantation is a safe and effective procedure to treat complicated Type I diabetic patients. It does carry significant potential for morbidity; therefore, it is essential that potential recipients understand these details prior to considering the procedure. Adequate preoperative screening for coronary artery disease is essential. The most difficult problem is dealing with early posttransplant dehydration and acidosis. More sensitive tools are needed to diagnose acute rejection in both combined kidney/pancreas recipients, as well as pancreas-alone grafts. Infectious complications are frequent, but most pose little morbidity. Currently, the incidence of early thrombosis is negligible. Even with these complications, overall excellent patient outcome demonstrates that kidney and pancreas transplantation should be the procedure of choice in well-selected Type 1 diabetics with end-stage renal disease. PMID- 1306696 TI - Pediatric liver transplantation at the University of Chicago Hospitals. AB - The concept of graft-reduction surgery in liver transplantation has revolutionized pediatric transplantation and soon may carry over into adult transplantation. Reduced-size liver transplants have virtually eliminated patient deaths while waiting for donor organs to become available by increasing the potential donor pool. This has shifted the distribution of pediatric liver transplant recipients to a younger age which more closely matches the needs of pediatric patients with end-stage liver disease. Split-liver transplants can create new grafts without increasing the donor supply. Living-donor liver transplantation not only increases the supply of organs but also creates uniformly good quality grafts that can be used electively in stable patients. The result is patient and graft survival rates that are better than those seen with cadaveric organs. Orthotopic auxiliary liver transplantation offers children with metabolic disorders the opportunity to correct their diseases without the risks associated with whole-organ replacement. PMID- 1306698 TI - The current status of the University of Tennessee, Memphis, experience in pancreas transplantation. AB - SPK transplantation is associated with excellent rehabilitation and greater improvement in posttransplant functional status than is KTA transplantation. This improvement is not just a function of the magnitude of the improvement experienced by a few patients but was seen in the majority of patients and the majority of our study parameters. Since pancreatic transplantation adds to the morbidity of kidney transplantation for the uremic patient, longitudinal evaluation which demonstrates added benefits from the restoration of euglycemia by pancreas transplantation is important. Such evidence generated by us (14) and others (15, 16) now provides the justification for continuing pancreas transplantation. PMID- 1306699 TI - Results of the National Kidney Transplantation Program in Norway. AB - 1. Of 2,003 patients starting renal replacement therapy for end-stage renal disease in Norway from 1983 through 1991, 83% were candidates for transplantation. The need for transplantations increased to 58 (50 first and 8 repeat) grafts PMP per year as the number of elderly patients increased. 2. There were 1,528 transplants performed at a rate increasing to 46 grafts PMP per year. The grafts were procured from LDs in 44% and CDs in 56%. Eighty percent of all patients in need were transplanted and 65% of all patients requiring replacement therapy for end-stage renal disease were treated by transplantation. The national waiting list and dialysis population remained almost stable. 3. Graft survival rates in recipients of first LD grafts (n = 593) were 91% and 77% at 1 and 5 years, respectively. One-year graft survival was 98% in HLA-identical grafts (n = 73), 91% in haploidentical grafts (n = 411), 89% in 2 haplotype-mismatched related grafts (n = 38), and 85% in spousal donor grafts (n = 71). Higher rates were observed in younger (< 55 yrs) patients. 4. Graft survival rates in recipients of first CD grafts (n = 688) were 78% and 59% at 1 and 5 years, respectively. The rates were 84% and 66% in younger (n = 342) versus 72% and 52% in older (> 55 years) (n = 346) patients. Death with a functioning graft caused approximately 45% and 75% of all graft losses in younger and older patients, respectively. Cardiovascular disease was the major cause of death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306700 TI - Renal transplantation at the University of Pennsylvania Medical Center: an update of results in the cyclosporine era. AB - This chapter presents a summary of living-related, living-unrelated, and cadaver renal transplantation performed at the University of Pennsylvania Medical Center between January 1984 and October 1992. Over the past 9 years, 895 patients (557 males, 338 females, mean age 42 yrs) received 942 renal transplants; 599 patients received kidneys from cadaver donors (n = 627) and 296 patients received kidneys (n = 315) from living donors of all types. During this period, 151 patients were retransplanted, sometimes more than once (159 total retransplants, 124 secondary grafts, and 35 third or more transplants). An analysis of patient ant graft survival rates (calculated by actuarial methods) for different categories of transplant recipients was performed. Black recipients, as a racial subcategory, had the poorest graft outcome, especially when followed over the long term. Graft survival rates for Black recipients who were retransplanted with cadaver grafts were even worse and were noted to be similar to the diabetic population that received cadaver retransplants (66% vs 62% at 1 yr and 32% vs 25% at 5 yrs). Diabetic recipients of living-donor transplants had excellent graft survival results, similar to nondiabetic, living-donor recipients (patient survival rates 98% and 92% vs 97% and 92% at 1 and 5 yrs; graft survival rates 92% and 82% vs 92% and 82% at 1 and 5 yrs). HLA-identical recipients of first cadaver grafts demonstrated the best outcome in the entire cadaver series (graft survival rates 91% and 83% at 1 and 5 yrs, respectively). HLA-identical recipients of second or more cadaver grafts had poorer results than expected (50% graft survival at 1 yr) despite a 100% patient survival rate. HLA-identical recipients of living-related grafts had the best graft survival rates (96% at 1 yr and 94% at 5 yrs) and superior graft survival rates for retransplanted grafts as well (100% at 1 and 5 yrs). We conclude that in the last decade, patient and graft survival rates for cadaveric and living-donor renal transplants have improved dramatically relative to the results obtained in the pre-CsA era. Long-term graft survival in Black recipients remains lower than in other races, suggesting the need to analyze other factors to explain poorer graft survival in this recipient population. Results in diabetic recipients continue to be excellent at our center, encouraging the continuation of our aggressive approach to try to transplant diabetics as early as possible, particularly when a living donor is available. PMID- 1306701 TI - Kidney transplantation in patients with type I diabetes: 26-year experience at the University of Minnesota. AB - With current immunosuppressive protocols, 1- and 6-year graft survival is similar in diabetic and nondiabetic kidney transplant recipients. Living-donor transplant recipients have significantly better outcome. Death with function and chronic rejection remain the 2 predominant causes of graft loss for diabetic recipients. Compared with national statistics on diabetic patient survival on dialysis, our data suggest that transplantation is the treatment of choice for diabetic patients with end-stage renal disease. PMID- 1306702 TI - Immunosuppression without prophylactic antilymphocyte preparations. AB - 1. Triple-drug immunosuppression following third party transfusion can result in graft survival equal to protocols that employ prophylactic antilymphocyte preparations. 2. T1/2 was statistically improved in cadaveric and living-related donor grafts in the CsA era. 3. Patients 65 years and older had an excessive death rate. Younger groups were admixed. Extreme youth was not a risk factor. 4. Black recipients had excessive late graft loss. 5. Diabetic recipients had only a slight decline in graft and patient survival rates. 6. First and multiple graft recipients had similar transplant survival rates. 7. Delayed graft function remains costly in this immunosuppressive scheme. PMID- 1306703 TI - Single-center experience of unrelated living-donor renal transplantation in the cyclosporine era. AB - Renal transplantation from the unrelated living-donor might be an alternative when the cadaveric or related donor is not available, because graft and patient survival rates are superior to those of kidneys from cadaveric donors and even comparable to those from related donors. Among the many factors that might contribute to these excellent results, we believe that the good quality of kidneys (lacking preservation or ischemic injury) is the most important one. In addition, our criteria for patient selection requiring well-matched HLA typing might partially contribute to our success. For the successful renal transplantation program using unrelated-living donors, high ethical standards, accumulated experience from living-related donor transplantation, and dedicated professionalism are strongly recommended. PMID- 1306704 TI - Factors influencing long-term outcome of living-donor kidney transplantation in the cyclosporine era. AB - To evaluate the effect that CsA has had on the weight of some factors previously considered influential on kidney graft survival rates in conventionally immunosuppressed recipients, we analyzed patient and graft survival rates for 524 consecutive living-donor first kidney transplants. All patients were transplanted at the Catholic Medical Center between 1984 and 1991 and treated with CsA. The data were stratified to reflect differences in a) HLA matching; b) acute graft rejection within 3 months posttransplant; c) donor sources; d) age; e) sex; f) graft number; g) diabetics; h) HBV status; i) DST; and j) number of pretransplant transfusions. Overall actuarial 5-year patient and graft survival rates were 86% and 77%. The actuarial 5-year graft survival rates for the HLA-identical, haploidentical, and mismatched groups were 93%, 75% and 80% (p = 0.3858), respectively. The actuarial 5-year graft survival rates in recipients with acute graft rejection (< 3 months) and without acute graft rejection were 55% and 80% (p = 0.0001). The actuarial 5-year graft survival rates for the HBV-positive and negative groups were 55% and 80% (p = 0.0048). The actuarial 5-year graft survival rates according to the number of pretransplant blood transfusions--0, 1 4, and over 5 units groups--were 65%, 80%, and 81% (p = 0.0026), respectively. We conclude that a) acute graft rejection within 3 months, b) HBV-positive, and c) pretransplant nontransfusion had a significant negative influence on long-term graft survival, whereas little or no effect was attributable to HLA matching, donor source, age, sex, graft number, diabetes, and DST. PMID- 1306705 TI - Perioperative fluid and drug therapy during cadaver kidney transplantation. AB - 1. For all outcome measures associated with delayed onset of urine output and the need for posttransplant dialysis, the prognosis is poor. Low 1-year graft survival of 49% and patient mortality of 13% associated with delayed function make it exceedingly important to identify measures that induce immediate posttransplant kidney function. 2. Intraoperative blood volume expansion with albumin improves short- and long-term posttransplant function at every level of analysis, including earlier urine onset, larger urine volumes, improved kidney function, decreased incidence of delayed and no function, and greater graft and patient survival. 3. Aggressive intraoperative blood volume expansion during cadaver renal transplantation enables the safe use of intraoperative verapamil without inducing hypotensive complications. 4. Intraoperative verapamil improves the decreased renal blood flow associated with poor function as seen after organ procurement and cold ischemia. 5. Clinical studies confirm previous animal research demonstrating that verapamil and other calcium antagonists prevent CsA induced deterioration of renal blood flow. 6. Several studies have demonstrated elevated CsA blood concentrations during concomitant treatment with verapamil and diltiazem but not with the dihydropyridine class of calcium antagonists. 7. Despite the higher CsA blood levels, kidney function, as determined by serum creatinine and glomerular filtration rate, improves with verapamil. 8. Verapamil given intraoperatively into the renal artery after revascularization improves renal function and reduces the need for posttransplant hemodialysis. 9. The combination of intraoperative verapamil and blood volume expansion acts synergistically, resulting in larger urine volumes, improved renal function, and decreased incidence of delayed function. 10. Most importantly, perioperative administration of albumin and verapamil independent of each other, significantly improves graft survival. 11. The beneficial effects of albumin are probably due to improved hemodynamics from increased blood and plasma volumes leading to better renal perfusion and prompt oxygenation. Secondly, blood volume expansion provides a safeguard against the intraoperative use of verapamil. The beneficial effects of verapamil on posttransplant outcome may be related to cellular protection from ischemia, selected vasodilation of the afferent arteriole, inherent immunosuppressive properties, and elevated CsA blood levels. PMID- 1306706 TI - Transplantation 1992: the year in review. PMID- 1306707 TI - Multifactorial analysis of renal transplants reported to the United Network for Organ Sharing Registry. AB - 1. From a multivariate log-linear analysis of 35,625 renal transplants between 1988 and 1991, center effects accounted for 28%, 45%, and 27% of all assignable variation in 3-month, 1-year, and 2-year outcomes, respectively. Although center variation dominated 22 other variables, most factors were relatively independent of transplant center (ie, a percent of factor variation due center less than 10%). Recipient race and health status were notable exceptions; both highly influenced by center affiliation. Centers also differed in the age mix of recipients and racial mix of donors in some epochs. Again, we found only extremely weak correlations among a center's 3-month, 1-year, and 2-year graft survival rates. 2. In order of 3-month accountability, the other important factors were PRA, donor age, recipient working status, year of transplant, HLA A,B mismatching, previous transplant, donor's death, donor relationship, recipient race, body mass, recipient age, cold ischemia time, donor race, donor kidney mode (ie, left/right kidney), original disease, and HLA-DR mismatching. Regarding 1-year outcome, the important factors were recipient race, donor age, donor's death, donor relationship, HLA-A,B mismatching, previous transplant, and recipient sex. Finally at 2 years, the important factors were recipient race, donor age, year of transplant, donor relationship, recipient sex, working status, donor's death, recipient age, CMV status, body mass, and donor sex. 3. Body mass, donor kidney mode, and CMV status were novel factors in our own multifactorial analyses of the UNOS Registry file. An elevated body-mass index (> 30 kg/m2) had a negative impact on short- and long-term graft survival. Recipients receiving left kidneys had nominal improvement in 3-month graft survival, but no impact thereafter. Survival rates over the 4 combinations of donor/recipient CMV statuses, suggest that this covariate was principally long-term and donor related. 4. It is noteworthy that graft failures in the 2 most recent transplant years, 1990 and 1991, have shown both short- and long-term declines, breaking stationary patterns previously reported in this series on clinical transplants. 5. The transitory nature of most transplantation factors was confirmed in this study, implying that future multifactorial studies in renal transplantation must include some mechanism for varying risks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306708 TI - Long-term kidney graft survival. AB - 1. More than 90% of long-term grafts were first transplants. 2. The percentage of long-term transplants from living-related donors decreased from 78% in the years prior to 1968 to 42% in the 1973-1977 period. 3. More than 60% of living-related long-term grafts were from sibling donors. 4. Among long-term survivors, there was no difference from the expected rates in the percentage of red blood cell groups. 5. HLA-A,B matching resulted in significant improvement in graft survival rates for both cadaver donor and related transplants. PMID- 1306709 TI - Thoracic organ transplants in the United States from October 1987 through December 1991: a report from the UNOS Scientific Registry for Organ Transplants. AB - 1. In 1991 there were 2,127 heart, 402 lung, and 51 heart-lung transplants performed in the United States. These numbers reflect increases of 27% for heart, over 1000% for lung, and a decrease of 31% for heart-lung transplants since 1988. 2. The number of programs performing heart transplants has increased by 16% since 1988, whereas the number of programs performing lung transplants has tripled over that time. 3. The most frequent primary indications for thoracic transplantation were: cardiomyopathy (45%) and coronary artery disease (41%) for heart; primary pulmonary hypertension (43%) and congenital/Eisenmenger's for heart-lung; and emphysema/chronic obstructive pulmonary disease (28%) and Alpha-1 antitrypsin deficiency (20%) for lung. 4. Average cold ischemic time increased gradually between 1988 and 1991: 2.7 hours for hearts transplanted in 1991 compared with 3.3 hours for heart-lungs, and 4.3 for lungs. 5. Between 1988 and December 1991, the following percentages increased significantly: pediatric heart and lung transplantations; non-White thoracic transplant recipients and donors; the use of thoracic organs from younger (< or = 5 yrs) as well as older (> or = 45 yrs) donors; and local utilization of thoracic organs. 6. For the entire period covered by this report, 1-year recipient survival rates were: heart 81.6%, heart lung 55.4%, and lung 67.2%. Patient survival was significantly lower in heart retransplants or when the primary indication for transplantation was the treatment of congenital disease. Between 1988 and 1991, 1-year survival appeared to have increased significantly for heart-lung and lung recipients. PMID- 1306710 TI - Center effect in the UNOS Renal Transplant Registry. AB - Based upon univariate and multivariate analyses of transplant center effects: 1. Among the 115 centers selected for these analyses, there was no correlation between 6-month graft survival rates and half-lives projected for grafts surviving 6 months. 2. There was no significant center effect for living-related donor transplantations. 3. Centers that had the poorest short- and long-term survival performed more cadaveric transplants with patients in poor health at the time of transplant, more often transplanted a recipient other than the one originally identified for a particular kidney, and more often transplanted kidneys with prolonged cold ischemia, and kidneys from pediatric (age 0-11) donors, older (ages over 50) donors, Black donors, or donors who died with cerebrovascular accidents. 4. After adjusting for 17 potentially confounding variables, the difference between the best and worst center groups was the second most detrimental factor (following broad sensitization) in the first 6 months and was the factor ranked ninth in long-term survival. 5. The transplant year has emerged as a significant factor in long-term survival. This suggests that the late loss rate for transplants performed after 1988 may be diminishing. 6. The health status of the patient at the time of transplant was the dominant factor affecting long-term survival. 7. The choice of outcome variable and the selection criteria used in center classification affect the magnitude of the center effect and its relationship to other significant variables that influence graft outcome. PMID- 1306711 TI - Regrafts. AB - 1. Retransplant survival rates have been increasing at a much faster rate than those of first transplants. The difference between first and second transplant 1 year survival rates has decreased from 8% in 1988 to 2% in 1991. 2. Second transplant recipients given 1-20 pretransplant transfusions had 3-5% higher graft survival rates than nontransfused patients or those given more than 20 transfusions. Transfusions for first or multirenal transplants had no significant impact on survival and in some cases, nontransfused patients had higher graft survival rates. 3. The duration of previous graft survival remains one of the best indicators of how subsequent grafts will survive. The 1-year regraft survival rate for second transplant recipients was 77% when the first transplant had survived longer than 1 year, 69% when first graft survival was 6 months to 1 year, and 60% when first graft survival was less than 3 months (p < 0.005, each comparison). 4. The HLA-DR1 phenotype was associated with higher graft survival than patients lacking HLA-DR1. The difference was 8% at 1 year for second graft recipients (p < 0.001) and 15% for multiply retransplanted patients (p = NS). 5. Repeating an HLA-A or -B locus antigen mismatch from a previous graft had no apparent effect on regraft survival rates. Repeating an HLA-DR locus antigen mismatch, either alone or in combination with other antigens, resulted in a 5-8% decrease in 1-year regraft survival. Although the difference was not statistically significant at 1 year, survival was significantly lower at 2 and 3 years for recipients with repeated HLA-DR antigen mismatches. PMID- 1306712 TI - Sensitization. AB - 1. The transfusion effect, which had its greatest impact in 1985, disappeared in 1989. Since then, transfused and nontransfused groups have had identical 1-year graft survival rates. 2. The percentage of nontransfused recipients reached nearly 50% in 1992. The amount of pretransplant transfusion blood has dropped from 7 units in 1982 to below 5 units in 1992. Whole blood and packed red cells were the preferred products, comprising 98% of total transfusions in 1992. 3. The transfusion effect was observed in both sensitized and nonsensitized transfused recipients until 1988, although the effect was greater in the nonsensitized group. Since 1989, the sensitized group of transfused recipients had an even lower 1-year graft survival rate, while the nonsensitized group had a slightly better survival rate than those with no pretransplant transfusions. 4. Although washed red cells, frozen red cells, and frozen plasma constituted only a small percentage of total transfusions, any pretransplant transfusion of these blood products still produced a transfusion effect. Since 1982, patients who received washed red cells, frozen red cells, or frozen plasma had 8% higher 1-year graft survival rates since 1982 than those who had no transfusions, a difference still patient in 1990. 5. The percentages of broadly sensitized recipients decreased significantly in the last decade. Even recipients who had very specific antibodies (PRA 1-10%) had significantly lower graft survival rates than those with no antibodies (PRA = 0). Patients with PRA 1-10% and those with PRA 11-50% had almost identical graft survival curves and the same half-life, whether first or regrafted recipients. Only 0-PRA patients could be distinguished as "nonsensitized." 6. Once patients were sensitized, any time pretransplant, the current PRA values had less meaning for predicting graft survival than the peak (historical) PRA values. Those with peak PRA 51-100% had the same graft survival rates regardless of their current PRA values. Peak PRA was more important than current PRA for predicting graft status. 7. The deleterious effect of a positive flow cytometry crossmatch (FCXM) was obvious in both first and regrafted recipients. The positive group had about a 10% lower 1-year graft survival rate than the FCXM-negative group. 8. The significance of the positive FCXM outweighed the current PRA values, especially in regrafted recipients and first transplant recipients with peak PRA values. 9. FCXM seemed to work only on patients who had a chance of being sensitized by HLA stimulation. There was no positive FCXM effect in nontransfused recipients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306713 TI - Disease effects and associations. AB - 1. The most common disease leading to end-stage renal disease were IDDM for Whites (36%), hypertensive NS for Blacks (26%), and CGN for Hispanics (35%) and Asians (47%). These racial differences should be taken into account in analyzing outcomes with respect to disease. 2. Differences in graft survival associated with different primary diseases were more apparent among Whites than Blacks. Race, rather than disease, was the dominant factor. 3. One-year graft survival was consistently highest for patients with IgA nephropathy (87%) and poorest for patients with SLE (78%). The difference across the spectrum of original diseases was significant (p < 0.001). 4. About 84% of White diabetics and 90% of those under age 50 had an HLA-DR3 or 4 tissue type compared with 50% of White donors (p < 0.001). The 1-year graft survival rate was 80% for DR3 or 4 IDDM patients and 74% for non-DR3/4 patients (p < 0.001). Black IDDM patients also had a significantly increased frequency of DR3 and 4 compared with Black donors (46% vs 32%, p < 0.001) and a similar trend toward higher graft survival, although the difference was not significant. 5. Of Whites transplanted with SLE, 60% had HLA DR2 or 3 compared with 47% of donors (p < 0.001) and those with DR2 or 3 had significantly higher 1-year graft survival rates. Similar trends were noted for Blacks with SLE. 6. HLA-DR2 was present in 46 of 72 patients (64%) transplanted for Goodpasture's syndrome, compared with 28% of donors. Despite the small numbers, 1-year grafts survival was significantly better in the HLA-DR2 group (p = 0.006). 7. Significantly higher graft survival rates were observed among patients with HLA-DR1 in non-HLA-DR-associated diseases (CGN, IN, NS, or PC) but not in HLA-DR-associated diseases such as IDDM and SLE. 8. There were significant differences in recipient age and sex distributions in the major disease groups. Blacks under age 50 had significantly poorer outcomes than comparable Whites. 9. Pretransplantation health status influenced graft outcome in all disease groups. Patients with IDDM or NS were generally less healthy and correspondingly more debilitated than patients with other diseases. 10. Diabetic given a simultaneous kidney-pancreas transplant had 83% 1-year graft survival compared with 78% for those given a kidney alone (p < 0.001). PMID- 1306714 TI - Preservation. AB - 1. There were no significant differences in 1-year graft survival rates comparing kidneys stored with 3 commonly used cold storage solutions (Collins', EuroCollins, and University of Wisconsin) over the past 12 years, even though preferences have changed sharply. 2. No significant differences in 1-year graft survival rates were noted when comparing kidneys preserved by pump perfusion and those maintained by simple cold storage. The lower incidence of delayed graft function for pump-preserved kidneys was at least partly attributable to a center effect. 3. Prolonged cold ischemia time (CIT) was associated with an increase in delayed onset of function. Of 2,718 kidneys transplanted within 24 hours, 21% did not function well within the first week. The fraction increased to 28% and 33% of kidneys transplanted between 25 and 36 hours (n = 1,858) and after 36 hours (n = 955), respectively (p < 0.01). One-year graft survival rates were 82%, 78%, and 76% for kidneys transplanted within 24 hours, between 25 and 36 hours, and after 36 hours, respectively (p < 0.01, each comparison). 4. HLA matching neutralized the impact of prolonged CIT completely. One-year graft survival was more than 86% in 715 recipients of 0 HLA-mismatched kidneys, regardless of CIT. For recipients of mismatched transplants, survival decreased by 5-6% as CIT increased from less than 24 to more than 36 hours (p < 0.01). Of the mis-matched kidneys with less than 24 hours CIT, up to 83% survived at 1 year compared with 87% of matched kidneys with more than 36 hours CIT (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306715 TI - Rejection episodes. AB - Based upon analyses of 40,671 kidney transplants reported to the UNOS Scientific Renal Transplant Registry between October 1987 and August 1992: 1. Twenty-four percent of the 21,923 recipients of first cadaver grafts experienced one or more rejection episodes during their transplant hospitalization, 52% during the first 6 months. At 12 months, only 40% of patients remained rejection-free. Patients who experienced any rejection during the first 6 months had a 72% 1-year graft survival rate compared with 95% for those who remained rejection-free (p < 0.001). 2. Recipients of transplants from living donors had a significantly lower incidence of rejection episodes. There was a clear effect of histocompatibility in comparing the incidence of rejection in HLA-identical sibling transplants (8% at discharge and 32% at 1 year) with that in 1-haplotype disparate transplants (22% at discharge and 52% at 1 year, p < 0.01 at each time point). Rejections were reported for 25% of transplants from other living donors at discharge and for 56% at 1 year, similar to the figures for cadaver transplants. 3. Histocompatibility also influenced the incidence of rejection in first cadaver donor transplants. Only 15% of recipients of 0-HLA-A,B mismatched kidneys had rejection episodes reported at discharge, compared with 26% of those who received kidneys completely mismatched for HLA-A,B antigens (p < 0.01). At 1 year, 56% of HLA-A,B matched patients remained rejection-free, whereas only 35% of those mismatched for 4 antigens had no reported rejection through the first year (p < 0.01). Considering HLA-DR antigen mismatches, 19% of the 0-antigen mismatched group had rejection episodes at discharge, versus 28% for those with 2 HLA-DR mismatches (p < 0.01), and at 1 year, the percentage who were rejection-free decreased from 48% to 40% and 34% with 0, 1, and 2 HLA-DR mismatches, respectively. 4. The incidence of rejection episodes decreased as the recipient's age increased. Patients under age 16 had the highest incidence prior to discharge (28%) and at 1 year (70%) compared with 17% and 47% at the same intervals in patients over age 60 (p < 0.01). 5. The donor's age also had a significant effect on rejection episodes. Transplants from pediatric and older donors had a higher incidence of reported rejections than those from donors aged 16-30, especially after hospital discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306716 TI - Kidney allocation under the UNOS point system: an update. AB - 1. The 1,480 patients awaiting cadaveric renal transplants at 14 Southern California transplant centers as of December 3, 1992, were compared with patients transplanted using a point system for one kidney and a hospital-based allocation for the second, or the current system allocating all locally procured kidneys by the point system with regard to several demographic parameters. 2. Of 1,472 waiting patients with sensitization data, 8.5% were broadly sensitized (> 80% PRA). Of the 737 kidneys allocated by the point system, 7% went to broadly sensitized patients, compared with 3% of 438 kidneys allocated by the hospitals (p < 0.001). 3. Of 1,470 waiting patients with information available, 23% were awaiting a repeat transplant. Under the point system, 18% of kidneys were used for repeat transplants compared with 9% of hospital-allocated kidneys (p < 0.001). 4. Of 1,434 waiting patients where the time waiting was available, 26% had waited 1-2 years, 12% 2-3 years, and 6% more than 3 years. Under the point system, patients waiting longer received significantly more kidneys than those recently added to the list: 35% had waited 1-2 years, 21% 2-3 years and 14% more than 3 years (p < 0.001). Kidneys allocated by the hospitals were transplanted to patients in approximately the same proportions as the waiting list: 29% to those waiting 1-2 years, 10% 2-3 years, and 3% more than 3 years. 5. Racial distribution of recipients was not significantly different under either allocation system from that of the waiting list. Whites comprised 39% of waiting patients, the same as the population of Los Angeles County.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306717 TI - Crossmatch prediction of highly sensitized patients. AB - 1. A subset of negative reactions of sera from highly sensitized patients to donor lymphocytes are predicted with high accuracy (96.5% negative correct). 2. The prediction is performed by a hybrid expert system (HES) which uses multiple knowledge of stochastic (SCORES), artificial neural net (ANN), and genetic algorithm (GA) techniques. 3. All knowledge for the T-cell predictions is derived from serological reactions of the investigated sera (93) to a large panel (284). 4. When analyzing 5 HLA Class I typing sera controls, HES performs better than a standard serum analysis method in 3 measurement categories: r value; percent correct; and percent negative correct. 5. SCORES and ANN produce the strongest complementary association. SCORES is the best method with low PRA sera, while ANN is better at predicting high PRA sera. GA performs very poorly with high PRA sera. 6. HES can acquire knowledge from any of the various methods used for serum screening and crossmatch testing. Therefore, there is no need for method standardization as each laboratory will produce its own program incorporating its patients' data. High standardization of HLA Class I typing is necessary. 7. Most recipients for whom donors are never selected by HES are in the PRA range of 97 100%. 8. Certainty level categorization of a crossmatch gives clinical flexibility in judgement of potential donors. 9. All programs are written in the C language and are portable to numerous platforms. HES is implemented on an inexpensive IBM-PC compatible computer and can calculate predictions quickly. 10. HES predicts negative crossmatches with enough accuracy to initiate an organ sharing protocol to increase the chance for highly sensitized patients to obtain a transplant. PMID- 1306718 TI - Analysis of United Network for Organ Sharing (UNOS) United States of America (USA) Pancreas Transplant Registry data according to multiple variables. AB - As of 1992, more than 4,200 pancreas transplants were reported to the International Pancreas Transplant Registry. Of these, more than 2,600 were performed in the United States, and of these, more than 2,100 have been transplanted since the inception of the UNOS Registry in October 1987. The analyses here are only of the UNOS data. Pancreas transplants performed in conjunction with a liver (either cluster or noncluster) or a heart were excluded from the analysis, and only those performed as a solitary procedure or in conjunction with a kidney were included. Emphasis was placed on those performed with the bladder drainage (BD) technique (96%). In the overall analysis of BD cadaveric pancreas transplants (n = 1,879), 1-year patient survival and pancreas graft function survival rates were 91% and 71%, respectively, 87% and 66% at 2 years, and 81% and 59% at 3 years. There were no differences according to gender, but 1-year graft survival rates were significantly higher in recipients 45 years or younger (72%) (n = 1,679) than in those older than 45 (64%) (n = 200). There were no significant differences according to graft preservation times of less than 12 (n = 749), 12-24 (n = 940), 24-30 (n = 79), and more than 30 (n = 9) hours, function rates at 1 year being 71%, 72%, 72%, and 44%, respectively. When analyzed according to the 3 major recipient categories (simultaneous pancreas/kidney transplants [SPK] [n = 1604]; pancreas after kidney transplants [PAK] [n = 166]; and pancreas transplants alone [PTA] [n = 109]), patient survival rates were no different (91%, 92%, and 92% at 1 year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (75%, 48%, and 49%, at 1 year, respectively). In the SPK group, kidney graft survival rates at 1 year were 84%. Outcomes were also compared according to whether induction immunotherapy included ALG, OKT3, or neither. In the SPK category, there was no difference among the protocols, with 1 year graft survival rates being 76% in the ALG (n = 838), 76% in the OKT3 (n = 416), and 72% in the Neither (n = 299) group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306719 TI - International Cell Exchange: 1992. AB - 1. This is a review of 1992 typing of 40 cells for Class I antigens and 18 cultured cell lines for Class II antigens through the International Cell Exchange. Serological typings were compared with DNA typing reports for Class II specificities. Presently, 290 laboratories participate in the monthly Class I exchange. Class II results were received monthly from 166 serology laboratories and from 36 DNA laboratories. 2. In 1992, 11 of the 16 A-locus antigens attained 95% or greater average detection. Nine of the 27 B-locus antigens showed 95% or better mean agreement levels. Antigens such as B46 and B70 continued to show improvement in detection in a 5-year period. 3. We compared discrepancy rates of 7 A-locus and 8 B-locus antigens typed 3 times or more. The rates for the B-locus specificities, especially for percentages of false negatives (ie, how often the antigen assignment was missed), continued to be greater than those for the A locus antigens. Nevertheless, the discrepancy rates of B35 and B70 decreased dramatically during the last 5 years. 4. We showed the number of laboratories with the total of false negatives and false positives. Nine laboratories achieved perfect records (0 false negatives and false positives) for all analyzed antigens in 1992. 5. Results of retyping of 3 donors over several years were shown to indicate improved antigen detection. 6. Recently recognized HLA-specificities, such as A2403 and B5102, were shown as cell variants studied in previous cell exchanges. Variants of B15, B16, and B40 families were presented, as well as several new A-locus antigens. 7. The low and high rates, in addition to the average detection levels, were indicated for a total of 27 (18 DR and 9 DQ) Class II specificities by serology and by DNA typings. Eight of the 15 DR/DRB1 specificities attained 90% or better average agreement by both serology and DNA. Three of the 9 DQ antigens achieved 90% or better average detection by both methods. 8. Confirmation by DNA typings was demonstrated for 8 Class II specificities with 60% or lower detection levels by serology; the average detection levels by DNA typing was 80% or greater. Confirmation of 2 splits of Class II antigens by DNA typing was shown in 3 cells. 9. The percent detection levels were calculated for 17 DRB1 alleles and 11 DQB1 alleles. Variation in agreement was observed for the Class II alleles. Two DRB1 and 3 DQB1 alleles had average detection levels of 80% or higher.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306720 TI - Phenotype frequencies of the class II (DR, DQ) DNA alleles by the patterns of sequence-specific primer mixtures (SSPM) in four different populations and the probable haplotypes between DRB1 allele and DQB1 allele. AB - From this study, it is clear that: 1. Most alleles of DRB1, DRB3, DRB4, DRB5, and DQB1 can be identified by 19 combinations of primers. 2. Among a total of 81 alleles, 54 of 64 were contained in the DRB1, B3, B4 and B5 loci, and all 17 DQB1 locus alleles were identified by this method. From this extensive population study and past serological experience, it is clear that: 3. SSPM, which uses only primers, not probes, is another tool that can be utilized to detect polymorphisms or microvariations in DNA sequence within the same locus. PMID- 1306721 TI - A ten-year prediction for kidney transplant survival. PMID- 1306722 TI - Worldwide transplant center directory. PMID- 1306723 TI - The UNOS OPTN (Organ Procurement and Transplantation Network) waiting list: 1988 through November 30, 1992. AB - Based on data from the OPTN Waiting List and the Scientific Registry between 1988 and 1992: 1. The number of registrations on the overall waiting list increased by 81% between December 31, 1988 and November 30, 1992. On November 30, 1992, there were 29,047 registrations for a transplant in the United States. Organ-specific waiting lists showing strong increases during the period were lung (1,277%), liver (262%), and heart (162%). The number of heart-lung registrants decreased during the period. 2. Overall, Whites comprised the largest percentage of waiting list registrants, followed by Blacks and Hispanics. This frequency distribution remained relatively constant between 1988 and 1991. On the organ-specific waiting lists, the percentage of Whites ranged from 80% on the liver waiting list to 90% on the pancreas waiting list. Blacks make up about 12% of the United States population, but about 32% of the kidney waiting list, due to the high incidence of end-stage renal disease among Blacks in the United States. 3. The frequency distribution of age on the waiting lists is shifting toward a greater proportion of potential recipients age 45 or older. This trend was especially true for the liver, lung, and pancreas waiting lists. 4. The percentage of highly sensitized registrants (PRA > or = 80%) on the kidney waiting list decreased by 8% between 1988 and 1991. The percentage of registrants with PRA less than 20% increased by 11.3%, probably as a result of longer waiting times for low-PRA registrants. 5. A result of the growth of the waiting lists was an increase in the median waiting time to transplant during the period. This effect was observed on every waiting list except the heart-lung. The wait for a liver transplant was the shortest (67 days in 1991), whereas the wait for a heart-lung transplant was the longest (543 days in 1990). 6. The overall death rate remained relatively stable, but was up slightly in 1991, when 6.1% of registrants died while waiting for a transplant (compared with 5.6% in 1990). The death rate on the heart-lung waiting list fell from 23.5% in 1988 to 14.8% in 1991, probably because of fewer heart-lung registrations. In 1991, the death rates were highest on the thoracic waiting lists (11.7-14.8%), followed by liver (9.3%), kidney (3.7%), and pancreas (3.0%). 7. The percentage of patients in the most urgent medical status categories remained stable on the heart waiting list and has decreased on the liver waiting list. PMID- 1306724 TI - Current status of lung transplantation--report of the St. Louis International Lung Transplant Registry. AB - There were 1,536 lung transplants reported to the St. Louis International Lung Transplant Registry as of September 1, 1992. The number of centers performing lung transplants increased each year. The 1- and 2-year actuarial survival statistics for all transplants were 68% and 60%, respectively. The most common indication for transplantation was chronic obstructive pulmonary disease, followed by idiopathic pulmonary fibrosis, emphysema secondary to alpha-1 antitrypsin deficiency, and cystic fibrosis. Among the total of 492 deaths reported (34%), sepsis was the leading cause of death. PMID- 1306725 TI - Report from the International Bone Marrow Transplant Registry. AB - The number of allogeneic BMTs performed worldwide continues to increase. In addition, the characteristics of patients, donors, and selected treatments are changing. In BMT for leukemia during the 1980s there was a marked increase in transplants for early disease, the use of unrelated donors, and utilization of preparative regimens without radiation. Although treatment-related mortality declined during this period, there was only a modest decrease in relapse rates, indicating the need for more effective antileukemia strategies. The IBMTR collects data from many centers, and, as a consequence, it is uniquely suited to examine clinical situations in which patient accrual at a single institution would be insufficient for a study to be performed. In such analyses, BMT was shown to be an effective treatment for Ph1-positive ALL. Patients tended to have earlier relapses and lower probabilities of LFS than Ph1-negative ALL but the differences were not statistically significant. BMT was also shown to be effective in patients with acute leukemia failing to ever go into remission, most of whom would die within the first 6 months following diagnosis. The IBMTR is a premier example of international scientific collaboration. Its success is a consequence of the desire of investigators throughout the world to combine their clinical data for statistical analysis in order to accelerate and improve patient care. PMID- 1306726 TI - Current status of unrelated-donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study. AB - 1. The International Marrow Unrelated Search and Transplant (IMUST) Study 1 provides novel prognostic data on outcome of unrelated-donor (UD) searches for patients with well-defined clinical characteristics. Case-types analyzed by multifactorial methods reveal the importance of HLA phenotype, ethnic mismatching, and stage of disease at search request, in predicting search outcome. White patients, with common HLA types and early disease, were least likely to suffer search failure. In contrast, searches for non-White patients with unusual HLA phenotypes and advanced disease were most likely to fail. Of importance, 70% of patients had HLA phenotypes defined as uncommon. 2. Overall donor yield at the 2 UK registries between 1989 and 1991 was 7%, significantly below expectations. Reasons for this shortfall are that theoretical predictions did not consider ethnic mismatch and logistical delays incurred by outdated UD search routines and most importantly HLA-typing inaccuracies. 3. IMUST Study 2 is a prospective multicenter-controlled cohort study comparing HLA-identical sibling donor (ID) and UD-bone marrow transplantation (BMT) for factors affecting BMT outcome. Generous support was provided by 83 BMT centers worldwide. An interim analysis of 165 UD- and 368 ID-BMT, with at least 6 months follow-up after BMT, is described. Unifactorial analysis showed a probability of engraftment at day 100 of 89% after UD- compared with 98% after ID-BMT (p < 0.001). Probability of Grades II-IV acute graft-versus-host disease (AGvHD) at 100 days was 52% after UD compared with 42% after ID-BMT (p < 0.01). Probability of overall survival at day 400 was 42% after UD- compared with 63% after ID-BMT (p < 0.001). Survival on day 400 of those patients receiving UD-BMT for early disease was encouraging at 52%. 4. Multifactorial analysis was performed on combined data from UD- and ID BMT cohorts to identify various factors predicting engraftment, AGvHD, and overall survival. Survival after UD-BMT was increased by center experience of UD BMT and the use of additional pretransplant immunosuppression. Survival was decreased in UD- compared with ID-BMT, by female donor to male recipient and poor risk disease. Engraftment was improved in ID- compared with UD-BMT, and after UD BMT at centers experienced in UD-BMT. Engraftment worsened with the use of ex vivo T-cell depletion for GvHD prophylaxis, in chronic myeloid leukemia, and in male recipients of female marrow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1306728 TI - Comparison of oral squamous cell carcinoma in younger and older patients in India. AB - This study examines the demographic, aetiological and clinico-pathological features of 37 patients with oral squamous cell carcinoma (SCC) who were less than 35 years old and a comparable number of patients who were greater than 60 years old. The study was undertaken at the Regional Cancer Centre, Trivandrum, India, between 1988 and 1990. In patients younger than 35 years old, oral SCC occurred more commonly in females, was apparent in all social classes and was associated with fewer aetiological factors. The tumours manifested predominantly as invasive lesions affecting the tongue and there was early spread to lymph nodes. By contrast, in patients older than 60 years of age, oral SCC was more common in males, occurred more frequently in social classes III and IV and was always seen in association with smoking, alcohol or pan chewing. These latter tumours presented as exophytic lesions of the buccal mucosa or gingivae and spread late to lymph nodes. The results indicate that the biological behaviour of oral SCC in young patients may be distinct from that occurring in older patients. PMID- 1306727 TI - Oral infection as a reason for febrile episodes in lymphoma patients receiving cytostatic drugs. AB - 56 patients receiving chemotherapy for non-Hodgkin lymphoma or Hodgkin's disease with curative intent were monitored for up to one year after initiation of treatment. During chemotherapy (mean duration 5.2 months), 26 of the patients (46%) suffered from 38 febrile episodes. In only 16 instances was an extraoral cause for the septicaemia found. However, severe dental infection, reflected in an elevated radiological index for the jaws, was found more frequently in patients suffering febrile episodes than in those without (P = 0.02). Moderate to severe gingival inflammation was observed during 22 (58%) of episodes. During 71% of the episodes various pathological findings were also recorded in the oral mucosa. No source of infection other than an oral one was found in 42% of the patients. Our results emphasise the importance of oral foci as the possible infection source in patients receiving intensive chemotherapy. PMID- 1306729 TI - Progressive 13-cis-retinoic acid dosage in the treatment of oral leukoplakia. AB - 16 patients with oral leukoplakia were treated with oral 13-cis-retinoic acid. The initial dose, given for 3 months, was 0.2 mg/kg/day, increasing by a further 0.2 mg/kg/day in successive 3 month cycles. The maximum dosage reached at 1.0 mg/kg/day, was given to only 2 patients (who received a total of 15 months treatment). However, 10 patients completed the cycle at 0.8 mg/kg/day (12 months treatment in total), but treatment could not continue due to toxicity (grade I and II), which was cutaneous, mucosal, and haematological (hypertriglyceridemia and hypercholesterolemia). There was grade III toxicity in the skin and mucosa in only 1 case, a patient treated at a dose of 1.0 mg/kg/day. The toxicity was reversible in all cases. 14 of the patients completed the trial. In 4 there were improvements graded as partial responses (PR) obtained at 0.2 mg/kg/day (3PR) and 0.6 (1PR) and there was one complete response (CR) obtained at 0.4 mg/kg/day. Overall there was thus an objective response rate of 36% who showed 50% or more reduction in lesion size. After the retinoic acid treatment was stopped, patients were followed-up for 12 months; 2 patients showed regression of the responses obtained after 6 and 9 months. This study shows that oral treatment with 13-cis retinoic acid at low dosages is efficacious and with minimal toxicity. It also shows that it is not feasible to treat these patients at doses above 0.8 mg/kg/day for long periods--mainly due to poor compliance. PMID- 1306730 TI - The prognostic value of cytometric DNA analysis in early stage tongue cancer. AB - In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies. PMID- 1306731 TI - Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer. AB - The presence of epidermal growth factor receptor (EGF-R) gene was determined in 84 patients with squamous cell carcinoma (SCC) of the oropharyngeal region--a highly prevalent, chewing-tobacco associated malignancy in India, using Southern hybridisation analysis of DNA extracted from primary tumor tissues. We observed a 3- to 8-fold amplification of EGF-R gene in 19/66 (29%) of the SCCs of the oral cavity, and about 30-fold EGF-R amplification in 2/18 (11%) hypopharyngeal cancers. Dot blot analysis of total RNA from several tumour tissues, revealed overexpression of the EGF-R gene in the examined patients, with the EGF-R gene amplified. 4 patients with single copy EGF-R gene, did not exhibit overexpression of the gene. Within our sample set, no correlation was evident between EGF-R gene amplification and clinico-pathological parameters of the malignancy. The amplification and overexpression of the EGF-R gene observed in the primary tumour tissues of 25% (21/84) of the human oropharyngeal cancers, indicate possible involvement of the gene in the pathogenesis of these cancers. PMID- 1306732 TI - Chemoprevention in the management of oral cancer: EUROSCAN and other studies. PMID- 1306733 TI - Vitamin A related compounds in the chemoprevention of potentially malignant oral lesions and carcinoma. PMID- 1306734 TI - Amalgam fillings, diagnostic dental x-rays and tumours of the brain and meninges. AB - A population-based case-control study of incident brain tumours in adults in Adelaide, South Australia considered possible associations of exposures to amalgam fillings and diagnostic dental X-rays with subsequent development of glioma and meningioma. The study, conducted in 1987-1990, recorded data from 110 subjects with glioma, 60 with meningioma and 417 controls. Principal findings were unexplained decreased risks for glioma associated with both exposure to amalgam fillings (age- and sex adjusted relative risk = 0.47, 95% confidence interval: 0.25-0.91; P = 0.02) and to diagnostic dental X-rays (adjusted relative risk = 0.42; 95% confidence interval: 0.24-0.76; P = 0.004), and a possible increased risk for meningioma in males exposed to dental X-rays. The choice of the unexposed comparison group is important in determining if an increased risk is associated with panoramic or full-mouth X-rays in glioma. PMID- 1306735 TI - Prevention of local relapses and new localisations of oral leukoplakias with the synthetic retinoid fenretinide (4-HPR). Preliminary results. AB - This paper analyses preliminary results of a randomised chemoprevention trial in patients surgically treated for oral leukoplakia started in 1988 at the Istituto Nazionale Tumori of Milan with the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR). To date 115 patients have been randomised, after surgical excision of oral leukoplakia, to receive 200 mg 4-HPR daily for 52 weeks versus no intervention. 80 patients completed the 1-year intervention, 41 in the control group and 39 in the 4-HPR group. During this period 12 local relapses or new lesions occurred in the control group and three in the 4-HPR group. Only 5 patients interrupted the intervention because of toxicity. No impaired dark adaptation was observed. It is concluded that 4-HPR is well tolerated and seems efficacious in preventing relapses and new localisations during the treatment period. This promising trend needs further confirmation. PMID- 1306736 TI - Fitting accuracy of indirect restorations: a review of methods of assessment. AB - The current interest in indirectly manufactured, tooth-coloured restorations has highlighted a need to identify factors pertinent to the success of both these and other indirect restorations. Although restoration longevity is limited by the degree of adaptation to the prepared tooth, there exists no standard method for either the assessment of marginal adaptation or the overall accuracy of fit. This review examines methods of assessment of both of these important parameters, and considers the problems associated with existing in vivo and in vitro techniques. PMID- 1306737 TI - Attachment and orientation of human periodontal ligament fibroblasts to lipopolysaccharide-coated and pathologically altered cementum in vitro. AB - Previous studies have suggested that bacterial lipopolysaccharides (LPS) may inhibit fibroblast attachment to root surfaces affected by periodontal disease. This study was carried out to investigate the effects of pathologically altered cementum and cementum coated with LPS on the attachment and orientation of periodontal ligament fibroblasts in vitro. LPS caused a maximum reduction of cell orientation of 26% after 5 days' culture compared with controls. However cells did not become attached and orientated to pathologically altered root surfaces. It was concluded that as yet unidentified factors other than LPS may have greater significance when considering optimal methods for the preparation of root surfaces for new attachment procedures. PMID- 1306738 TI - Mandibular guidance prostheses following resection procedures: three case reports. AB - Unilateral loss of mandibular continuity creates problems in prosthetic reconstruction. For dentate patients, palatal guide ramps or mandibular guide flange prostheses are indicated. Edentulous patients are much more difficult to retrain in mandibular movements, but complete dentures designed with stabilising occlusal contacts can be successful in compensating for the deviation. Three case reports are presented. PMID- 1306739 TI - Early in vitro marginal microleakage associated with different lining materials under Class II amalgam restorations. AB - The aim of this study was to determine which dental cavity lining material exhibited least microleakage when used under amalgam. Extracted premolar teeth, prepared with Class II cavities, had one of three lining materials (cavity varnish, zinc oxide-eugenol or light-cured glass-ionomer) placed. Following restoration the teeth were immersed in eosin and sectioned. Sections were subjected to image analysis measuring the linear leakage and area of spread into coronal dentine. Percentages in relation to restoration length and the area of crown dentine were calculated. Light-cured glass-ionomer cement liner significantly (P < 0.05) reduced all aspects of the microleakage parameters studied. PMID- 1306740 TI - Dental stone and improved dental stone surface hardness: the effect of the addition of potassium salts. AB - Changes in dental stone and improved dental stone surface hardness observed when prepared with aqueous solutions of potassium salts (K2SO4, KCl, KF, KBr, KNO4, KMnO4, K2Cr2O7) in concentrations of 0.5-5.0% were investigated. Parallel studies were carried out on dental stone and improved dental stone prepared with distilled water and crystallised in contact with alginate impression material, previously immersed in the above solutions for 2 minutes. Vicker's hardness tests were performed 3 hours and 24 hours after the initial set. The surface hardness of dental stone and improved dental stone is increased significantly by either method. The most effective hardening solution is potassium sulphate in concentrations of 0.5-5.0%. The degree of increase in surface hardness is directly proportional to the concentration of the solutions and proportionately greater at a shorter time (3 hours after the initial set). PMID- 1306741 TI - A comparative study of the attitude of dental students towards the elderly. AB - The aim of this study was to assess the attitudes of dental students towards the elderly in the two dental schools in Israel. The study population comprised 180 dental students currently enrolled in the two dental schools in Israel. The response rate was 59% and 92% for the students in Tel Aviv and Hebrew University respectively. The self-administered questionnaire measured attitudes using the Rosencranz and McNevin Aging Semantic Differential Scales. Students' attitudes were observed to be more or less neutral. No differences of significance were observed between the students of the two schools. Social contact with and experience in treating the elderly did not seem to change students' attitudes and their desire to work with elderly patients in the future. Further development of the curriculum should be implemented in order to try to change students' attitudes towards the elderly from neutral to positive for the benefit of the provider and society. PMID- 1306742 TI - Dental needs of residents and carers in elderly peoples' homes and carers' attitudes to oral health. AB - The dental needs of elderly people in residential homes and of their carers were investigated. Also, the carers' attitudes to oral health for themselves and the elderly residents were explored. Professionally diagnosed or normative need was greater than lay persons' perceived need in both groups. Overall, carers' attitudes towards their own and the residents' oral health were positive. However, carers had experienced a lack of formal training opportunities for mouth care and 93% requested education in oral hygiene procedures. It is recommended that the dental team develops and provides oral care programmes which will enable carers to provide routine hygiene support for the residents. PMID- 1306743 TI - [The pacemaker of dominating motivation]. PMID- 1306744 TI - [The contractile properties of the frog muscle fiber in the intact and the skinned states]. AB - The comparison of force-velocity (p-V) relation was made for live and chemically skinned frog skeletal muscle fibers. The latter fibers revealed steeper p-V curves. Maximal isometric tension in these fibers was 27 per cent less. The maximal velocity of unloaded shortening was 15 per cent greater. PMID- 1306746 TI - [The characteristics of the bile-secreting function of the liver and its regulatory mechanisms in ruminants]. AB - The function of gall secretion and the latter's composition were found to be regulated by the hypothalamic nuclei, amygdala and hippocampus in goats. The liver function was studied in starvation, feeding and repletion. PMID- 1306745 TI - [The contractile activity of the lymphatic microvessels and the role of opioid peptides in its regulation]. AB - The lymphatic microvessels of the rat mesentery do not contract rhythmically. Adrenaline and naloxone modulate the lymph-activating effect of opioid peptides (leu-enkephalin and dalargin). PMID- 1306747 TI - [The corticohypothalamic interrelationships during the acquisition and realization of a conditioned reflex]. PMID- 1306748 TI - [The temperature changes in different organs during immersion hypothermia]. AB - Precise thermometry of the brain, liver, rectum, muscles and skin surface was performed in white rats in conditions of immersion of the body in water with the temperature 1 degree C. Breathing arrested within 15-18 min after immersion, their brain temperature being 16.7-18.2 degrees C, liver temperature 12.7-15.2 degrees C, rectum--10.4-15.5 degrees C, muscle 8.3-12.0 degrees C, skin surface- 1.6-5.0 degrees C. PMID- 1306749 TI - [Heart mechanics and energetics during progressive hypothermia]. PMID- 1306750 TI - [Oxygen transport and gas exchange in rats under immersion hypothermia]. AB - Changes of the oxygen consumption and the main parameters of the blood respiratory function as well as oxygen transport, were studied in Wistar rats under conditions of immersion hypothermia (with rectal temperature 15-13 degrees C). From the viewpoint of the oxygen exchange, the rectal temperature 20 degrees C was found to be the critical level of the hypothermia. PMID- 1306752 TI - [The cholinergic mechanism of the stimulation of pancreatic secretion by enterosorbents]. PMID- 1306751 TI - [Changes in the water-salt composition of alveolar and ductal milk in the white mouse when accumulated in the mammary gland]. AB - The ion and water contents revealed a 25-41% lower Na level in the duct than in alveolar secret in lactating albino mice through 1 to 7 and 24th hour of suckling. The data obtained suggests dynamic properties of alveolar and duct epithelium in mice. PMID- 1306753 TI - [Konstantin Viktorovich Sudakov (on his 60th birthday)]. PMID- 1306754 TI - [The biological mechanisms of a congenital predisposition to alcoholism]. AB - In descendants of white rats with chronic alcoholic intoxication, the contents of DA in the brain and blood plasma, characteristics of GABA and opiate brain receptors, the contents of cAMP and other substances were studied as well as the c-fos gene expression. The data obtained suggest a considerable role of the changes in the DA system functions in the genesis of pathology in these descendants. PMID- 1306756 TI - [The hypothalamo-hypophyseal-adrenocortical system: the patterns in its functioning]. PMID- 1306755 TI - [The uncoupling of the functioning of the force generation and ATP hydrolysis centers in the myocardial myofibrils in experimental informational disease]. AB - Active and rigor force generation under the effect of electrostatic charge, the temperature and pCa, was significantly decreased in informational experimental disease. Other significant changes on the molecular level occurred in cardiomyocyte contractile apparatus in conditions of experimental informational disease. PMID- 1306758 TI - [The manifestation of "learned helplessness" in rats with different capacities for active avoidance]. PMID- 1306757 TI - [The efferent functions of the sensory endings of the autonomic peripheral system]. PMID- 1306759 TI - [An improvement in the cognitive characteristics of monkeys induced by an antioxidant: the neurophysiological correlates in the visual cortex]. AB - Administration of oximetacyl considerably improved the cognitive characteristics of the processes of delayed visual recognition, increased auto- and cross correlation coefficients in the responses of groups of neurons. The data obtained suggests nootropic properties of oximetacyl and participation of visual cortex of the monkey brain in realisation of these properties for improvement of the cognitive characteristics. PMID- 1306760 TI - [The effect of puncture actions on the ocular hypertension caused by chronic stimulation of the hypothalamus and amygdaloid body]. PMID- 1306761 TI - Advances in nutritional care of medical-surgical patients. AB - Malnutrition and its related complications occur at an alarming rate in medical surgical patients. New technology and other advances in clinical nutrition can now significantly enhance the nutritional care that medical-surgical nurses provide to their patients. PMID- 1306762 TI - Standards of clinical nursing practice: a link to quality of care. AB - The impact of nursing care on client outcomes must be visible if nursing is to obtain its share of the health care dollar. The first step in substantiating nursing's input on health care is to describe the responsibilities for which nurses are accountable. The ANA Standards of Clinical Nursing Practice (1991a) identify those responsibilities, setting the stage for implementing practice guidelines. PMID- 1306763 TI - Effectiveness of glove barriers used in clinical settings. AB - Gloves are the most common barrier used to prevent the transmission of microorganisms between patients and nurses, and clinicians should be familiar with factors that affect glove choice, including the type of unit, exposure to bloodborne pathogens, tasks performed, and personal safety. In addition to selecting the proper gloves for clinical practice, nurses can play an important role in the evaluation, quality control, and development of new effective barriers for hand protection. PMID- 1306765 TI - Clinical scholarship: publishing clinical excellence. AB - Clinical scholarship is an important professional responsibility for clinically excellent nurses. Nurses with publication goals should develop publishable ideas for a target journal, adhere to the basics of good writing, consider the special requirements of clinical journals, and address issues of authorship and professional goals. PMID- 1306764 TI - A nursing perspective on advance directives. AB - The nurse's role in implementing the Patient Self-Determination Act is often unclear. This article describes the clinical use of advance directives, discusses related ethical concepts, and identifies methods nurses could use for initiating discussions about advance directives. PMID- 1306766 TI - Implementing nurse case management in a community hospital. AB - A nursing case management system was implemented on the medical-surgical unit of an 86-bed community hospital using a four-phase process. The development and implementation processes are described. Program evaluation indicated that the application of the model resulted in benefits for patients, care providers, and the institution. PMID- 1306767 TI - Advance medical directives after Cruzan. PMID- 1306768 TI - Managing the violent addicted patient in the medical-surgical setting. PMID- 1306769 TI - Growth hormone: not just for the young anymore. PMID- 1306770 TI - [Effect of insulin therapy on abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetic rat]. AB - By use of histomorphometry and photon and physical, calcium homeostasis, bone morphology, bone mass and bone growth were studied in freely fed control, streptozotocin-induced diabetic, long-term and short-term insulin treated diabetic rats 14 weeks after the induction of diabetes. We conclude that untreated chronic streptozotocin-induced diabetic rat could result in abnormal bone and mineral metabolism, which is characterized by hypercalciuria, hyperphosphaturia and hyperphosphatemia, significant bone loss and growth arrest. The extent of bone loss correlated with the duration of the disease process. The anatomical basis of bone mass reduction is the diminution of osteoblasts activity which results in reduction of bone formation and insufficient bone calcification and relative increment of osteoclasts activity. Thus, bone resorption overweight bone formation leading to a negative balance of bone remodeling. The effect of PTH and CT on bone changes in diabetic rats can't be affirmed in our experiments. It is probable that metabolic disorder and/or insulin deficiency has a direct effect on bone changes. Insulin therapy started earlier in the course can prevent and somewhat later can completely normalize the altered skeletal morphology of diabetic rats. Whether this result is due to direct effect of insulin on skeletal tissue or through the correction of metabolic disorder remains to be resolved. PMID- 1306771 TI - [The relationship between plasma atrial natriuretic peptide (ANP) and glomerular ANP receptors in 5/6 nephrectomized rats]. AB - Chronic renal failure was induced in male Wistar rats with 5/6 nephrectomy (group I) and sham-operation was carried in the controls (group II). The results showed that in group I, plasma ANP levels increased progressively as Scr elevated. The plasma levels of renin and angiotensin raised simultaneously as compared with the controls (P < 0.001). At the 20th week after operation, urine volume and Na decreased significantly (P < 0.05) and the number of glomerular ANP receptors decreased significantly at the 12th week (P < 0.05) and 20th week (P < 0.01). Our data suggest that in 5/6 nephrectomized rats: 1. The elevation of plasma ANP level might be partly caused by damage of glomerular receptors. 2. The elevated plasma ANP could not cause its diuretic, natriuretic, blood pressure depression and R-A inhibition effect due to the damage of kidney ANP receptors. PMID- 1306772 TI - [Metabolism of serum lipoprotein in hypothyroidism]. AB - The changes of serum lipids concentrations in 15 patients with primary hypothyroidism were studied. 9 euthyroid persons in the similar age group with patients were selected as a control group. The serum levels of total and LDL cholesterol, TG, ApoAI, ApoB and ApoCII in patients before treatment were all higher than those of the control group. They decreased to normal level after treatment. The mean values of total cholesterol decreased from 6.7 mmol/L to 4.1 mmol/L, TG decreased from 2.5 mmol/L to 1.0 mmol/L, LDI-ch from 3.9 mmol/L to 2.4 mmol/L, ApoAI from 1.9 g/L, to 1.3g/L, ApoB from 1.2 g/L to 0.7 g/L and ApoCII decreased from 6.9 mg/dl to 3.9 mg/dl. There were no differences of HDI-ch level between patients before treatment and normal controls, HDI-ch level of patients only slightly decreased after treatment. Soon after the thyroid hormone treatment, all parameters of serum lipids, not including HDI-ch, were improved, as TT, level became normal, although the levels of TT4 was still not reached to normal level. PMID- 1306773 TI - [Factors influencing carboxyhemoglobin kinetics in inhalation lung injury]. AB - Anesthetized dogs were ventilated with 1% carbon monoxide (CO) in air for 10 minutes to produce CO poisoning and then with room air (n = 5) or pure oxygen (n = 5) for 3 hours as control. Acute lung injury was produced by intratracheal injection of 0.1 N HCl (2 ml/kg) 30 minutes before CO poisoning in another 10 experimental dogs. Arterial blood gas and carboxyhemoglobin (COHb) were monitored before and after CO poisoning. Pharmacokinetic analysis was used to find the half time of COHb elimination (T 1/2 beta). Pulmonary shunt was measured before CO poisoning in the injured dogs. Half-time of COHb elimination was prolonged in the injured dogs resuscitated with air as compared with dogs in the control group (275% +/- 28 vs. 203 +/- 24 min., P < 0.05); Oxygen accelerated COHb excretion in both injured and control animals. No significant correlation was found between T 1/2 beta and Qs/Qt in the injured dogs ventilated with air or oxygen. A negative linear relationship was found between T 1/2 beta of COHb elimination and the pre CO-poisoning PaO2 (r = -0.98, P < 0.005) in the injured dogs treated with oxygen. The data suggest that hypoxemia may represent the underlying mechanism of altered COHb kinetics in acute inhalation lung injury. PMID- 1306774 TI - [Reaction of serum growth hormone in patients with endemic cretinism to arginine and clonidine in continuous excitement tests]. AB - Reaction of serum growth hormone in cretins whose pituitary and thyroid function have returned to normal in IDD-control by using iodized salt to arginine and clonidine in continuous excitement tests ws observed. The result is that during the phase of clonidine excitement, serum growth hormone in cretins was obviously lower than that in normal controls and the reaction peak value, maximum increase value and reaction time all markedly lower than those of the normal controls. 3 cases (18.8%) had no excitement reaction during the phase of arginine excitement, 8 cases (50.0%) no reaction during the phase of clonidine excitement and 2 cases (12.5%) no reaction in the entire process of continuous tests. The results indicate that patients with cretinism suffer from low reserve function of pituitary growth hormone and insufficiency of synthesis even after ther thyroid function has returned to normal. PMID- 1306776 TI - [Factors predicting mortality in idiopathic dilated cardiomyopathy]. AB - A study of factors predicting mortality was performed in 69 patients with idiopathic dilated cardiomyopathy by analyzing 14 parameters according to clinical, electrocardiographic and echocardiographic findings. On admission 64% of the patients were in NYHA functional class 3 or 4. During a mean follow-up period of 18 months 43 patients died; 31 of refractory heart failure and 12 suddenly. 1 year survival was 58%. Multivariate analysis (Cox model) revealed that the independent predictors for mortality due to refractory heart failure were left ventricular enddiastolic diameter, NYHA functional class and systolic blood pressure; the presence of tricuspid regurgitation predicted mortality due to sudden death. PMID- 1306775 TI - [Endoscopic injection sclerotherapy for esophageal varices: studies on methodology and complication]. AB - From November 1985 to February 1991, sixty patients were randomized to three groups of intravariceal sclerotherapy: (1) many punctures of low quantity sclerosant, (2) one puncture of large quantity sclerosant, and (3) one puncture of large quantity sclerosant with transendoscopic balloon. The early effects and complications were investigated. Varices eradication was reached 91.2% in group 1, significantly higher than group 2 (58.3%) (P < 0.05), similar to group 3(89.9%). However, balloon group (group 3) required shorter duration than group 1 (12.6 vs. 21.7 days) (P < 0.05). There were no significant differences in complications, but all 6 esophageal stenosis were in group 1, recurrent bleeding was 11.4% in group 1.35.7% in group 2 and 0 in group 3 during sclerotherapy sessions. Further more, we found though attempted to inject into variceal veins, accurate intravariceal injection reached only 46.8% in accordance with venographic findings. We conclude that sclerotherapy with transendoscopic balloon seems to be more simple, safer, and required short time to produce successful variceal sclerosis. PMID- 1306777 TI - [Amylin and non-insulin dependent diabetes mellitus]. PMID- 1306778 TI - [Pathogenesis, prevention and treatment of osteoporosis]. PMID- 1306779 TI - [Allergen-stimulated release of prostaglandin E, F2 alpha by alveolar macrophages from patients with allergic asthma]. AB - Bronchoalveolar lavage (BAL) was performed in healthy subjects (n = 12) and patients with bronchial asthma (n = 11). Between the two groups there was no significant difference in the total number of cells and the percentage of alveolar macrophages (AM), lymphocytes (L), neutrophils (N) and eosinophils (E) in BAL fluids. When AM were cultured in vitro and stimulated with dermatophagoides farinae (DPF) antigen, the amount of PGE released by AM was significantly increased in the asthmatics. When the asthmatics, AM were sensitized with specific IgE positive serum and stimulated with DPF, they released more PGE and PGF2 alpha than those when specific IgE negative serum was used (P < 0.01). The PGE/PGF2 alpha ratio was significantly decreased. There was positive correlation between the decreased value of PGE/PGF2 alpha and patients, MCH-PC20. The increase in the amount of PGE and PGF2 alpha released and the decrease of PGE/PGF2 alpha ratio might play an important role in the pathogenesis of allergic asthma. PMID- 1306780 TI - [Immunoenzymatic labeling of monoclonal antibodies for surface antigens of T cells using immune complexes of APAAP in patients with interstitial lung disease]. AB - The use of unlabeled antibody bridging technique with alkaline phosphatase monoclonal anti-alkaline phosphatase (APAAP) complexes makes it possible to solve the problem of short durability of immunofluorescent staining and the problem of nonspecific endogenous enzyme interference of blood cells with immunoperoxidase method. The technique of APAAP allows satisfactorily to demonstrate the cytoplasmic and surface membrane antigens of T-cells both in peripheral blood and bronchoalveolar lavage fluid (BALF). With the technique studied, the subsets of T lymphocytes simultaneously in both peripheral blood and BALF of 26 patients with interstitial lung disease and of 16 apparently healthy subjects. The results showed: (1) In patients with interstitial pulmonary fibrosis (IPF) CD8 cells in BALF were higher in number than those in peripheral blood and BALF of normal subjects (P < 0.01). It is suggested that abnormalities of T-Lymphocytes might also play a role in the pathogenesis of IPF. (2) CD4 cells in BALF of patients with sarcoidosis were significantly higher in number than those in other groups (P < 0.01). However, CD8 cells in BALF of patients with sarcoidosis were lower in number than those in others (P < 0.01). The higher ratio of CD4/CD8 was found in sarcoidosis patients during active stage. The findings suggested that change of the ratio of CD4/CD8, as an immunoregulatory abnormalities in lung, could be regarded as one of parameters in assessing the activity in patients with sarcoidosis. PMID- 1306781 TI - [The use of thoracoscopy in the diagnosis and treatment of chest diseases]. AB - The procedure and results of thoracoscopy by using a fiberoptic bronchoscope and rigid cold-light thoracoscope in 76 cases with chest diseases of unknown causes were reported. The positive diagnostic rate was 89.5% (68/76). The histologic diagnosis following thoracoscopic biopsy in 65 patients was compared with the findings at follow-up, the results showed the sensitivity being 87.7%, specificity 100% and diagnostic accuracy 89.2%. 3 cases with persistent or recurrent spontaneous pneumothorax were cured by Nd-YAG laser transendoscopically. 5 patients with malignant pleural effusion were treated with intrapleural talcum powder under thoracoscopic control, 4 of them obtained complete pleurodesis. There were only minor complications: transient fever in 40 cases and local subcutaneous emphysema in 7. It was concluded that thoracoscopy is simple, safe, reliable and practical in the diagnosis and treatment of chest diseases. It should be popularized clinically. PMID- 1306783 TI - [Blunted growth hormone response to hGRF 1-29 NH2 in patients with non-insulin dependent diabetes mellitus]. AB - Basal serum growth hormone and response of GH to GRF in 10 patients with noninsulin-dependent diabetes and in 10 control subjects were studied. The basal GH level in NIDDM was higher than that in control subjects. There was a significant difference. After an intravenous bolus of hGRF 1-29 NH2 with the dose of 1 microgram/kg body weight, GH (Peak level-basal level) decreased in NIDDM patients in comparing with control group (P < 0.05). These findings may suggest that the pituitary GH reserve is reduced in patients with NIDDM. There exists some defect in central GH control in diabetics with enhanced somatostatin secretion and abnormal sensitivity of the GH secretion cells to a variety of regulatory factors including GRF, glucose, amino-acids, free fat acid. PMID- 1306782 TI - [Dynamic changes in the platelet granule membrane glycoprotein level in patients with acute myocardial infarction]. AB - Platelet granule membrane glycoprotein (GMP-140) level was measured by using 125I labelled monoclonal antibody (SZ-51) in 20 patients with acute myocardial infarction in the first three days and at the first three weekends. The correlation of severe arrhythmia and administration of aspirin with platelet GMP 140 in AMI were studied respectively. It is shown that platelet GMP-140 increased significantly in the first three days after AMI, then it dropped quickly, but remained at high level as compared with the controlled group till the third weekend (P < 0.01). Platelet GMP-140 level was higher in the first three days than at the first three weekends (P < 0.01). The changes of platelet GMP-140 have not been shown to be related with severe arrhythmia or administration of aspirin (P > 0.05). The results indicated that the platelets in AMI are activated continuously in the first three weeks after infarction; it might be thought as an important index of coronary artery thrombus formation. PMID- 1306784 TI - [Continuous albendazole therapy in alveolar echinococcosis--evaluation of therapeutic effect with computerized tomography and ultrasonography]. AB - Fifteen cases of alveolar echinococcosis were treated with albendazole in a dosage of 20 mg/kg/d x 30 days for 12-60 courses (25.8 courses in average) and were followed up 1-7 years (48 months in average) with computerized tomography and ultrasonography. Abdominal pain in all the cases, jaundice in 4 and hemoptysis in disappeared 2. In 13 of the 15 cases, the hepatic lesions reduced in size. Among 9 cases examined with computerized tomography, the hepatic lesions were completely calcified in 5 and enclosed with calcified walls in 3. Only one patient with huge and extensive hepatic lesions showed no apparent improvement. No severe adverse reaction was observed. Evidently albendazole was effective in the treatment of alveolar echinococcosis. PMID- 1306785 TI - [Immunohistochemical localization and serum testing for ferritin in malignant histiocytosis]. AB - Localization of ferritin with immunohistochemical staining was carried out in thirty six cases of malignant histiocytosis (MH). The positivity rate for ferritin was 100 per cent. Ferritin was found to exist in the cytoplasm of the tumor cells. Image analysis showed that ferritin level in the well-differentiated histiocytes (1.2314) was higher than that in the atypical histiocytes (0.7181) (P < 0.01). Ten MH patients showed surprising high serum ferritin concentration (1482.3 ng/ml) than that in normal. Our data suggest that ferritin is the tumor associated antigen in MH. The synthesis and release of ferritin by MH tumor cells is the important cause for the high concentration of serum ferritin in patients. PMID- 1306786 TI - [The causes, significance and treatment of emotional disturbances in patients with internal diseases]. PMID- 1306787 TI - [Observation of prosthesis movement after implantation of the bipolar artificial femoral head]. AB - The follow-up results of the movement of two components of hip prosthesis in 30 cases at different times after implantation of bipolar artificial femoral head were reported in this paper. It was demonstrated that the motion at both bearing surfaces in all cases was present 3 months-3 years after operation, and the motion range was not reduced with time. Therefore, the movement of bipolar artificial femoral head could be maintained within at least 3 years after implantation. PMID- 1306788 TI - [Complications caused by artificial hinge knee joint]. AB - Artificial hinge knee joint was used in 25 patients with bone tumors around the knee joint. 23 patients were followed on the average for 3 years and 3 months. Complication was noted in 10 patients including infection in 7 (5 short-term, 2 long-term), broken joint in 1 patient and loosening in 2. The causes for complication and counter-measures were discussed. PMID- 1306789 TI - [An experimental study of the process of bony ingrowth into inorganic bone particle impregnated bone cement]. AB - A composite of inorganic bone particles formed with bone cement in certain proportion was implanted in the proximal femora of 15 New Zealand rabbits. The animals were sacrificed in batches at different intervals after implantation and specimens were sectioned for scanning electron microscopic (SEM) observation and push-out test. SEM showed that the bone particles in the composite were in contact with each other and forming bony pathways. The gaps between inorganic bone particle bone cement and cortical bone were filled at first with collagen fibrils which were interwoven to form collagen fiber bundles and then mineralized to assume woven bone. The bone particles became smaller in size and were enveloped, absorbed and replaced by new bone structure gradually reaching the depth of bone cement along the pathways formed by bone particles. The shear strength of the cement-bone interface was increased subsequently. PMID- 1306790 TI - [The biological fixation strength of the bone particle impregnated bone cement]. AB - This article reports the result of the comparative study on the biological fixation strength of two kinds of bone particle impregnated bone cement. Organic and inorganic bone particle impregnated bone cement were implanted into alternative side of the upper femurs of New Zealand rabbits. The cancellous bone and cortical bone segments of the implanted femurs removed at intervals of 1, 2 and 3 months after operation were subjected to push-out test. In cancellous bone segment, shearing strength of cement-bone interface was increased gradually, but no significant difference between these two kinds of cement after 3 months operation. In cortical bone segment, the interface shearing strength was lower than that of the cancellous bone, but it increased rapidly from 1 month, especially for the organic bone particle bone cement, after 3 months operation the interface shearing strength had a significant difference between the two kinds of cement. More prominent biological fixation effect showed in the organic bone particle group. PMID- 1306791 TI - [Influence of vacuum mixing on mechanical properties of homemade bone cement]. AB - Porosity, density and rotating bar bending fatigue life of homemade bone cement are analyzed with scanning electron microscopy for two different mixing techniques: manually vacuum mixing and manually non-vacuum mixing. By vacuum mixing the rotating bar bending fatigue life is increased from 0.98 x 10(4) +/- 0.31 x 10(4) to 1.33 x 10(4) +/- 0.17 x 10(4) (P < 0.05), density increased from 1.0638 +/- 0.0005g/cm3 to 1.1024 +/- 0.0068g/cm3 (P < 0.05), porosity reduced from 10.35% +/- 2.33% to 5.83% +/- 1.74% (P < 0.05), and incidence rate of big air inclusion reduced from 5.93% to 0.9%. We believe, vacuum mixing technique of bone cement should be recommended as a routine procedure to prevent aseptic loosening of prosthesis after total joint arthroplasty. PMID- 1306793 TI - [Ectopic ossification following total hip replacement]. PMID- 1306792 TI - [The filling of bone-implant gaps with autograft, allograft/autologous red marrow and BMP/collagen in animal experiment]. AB - In order to compare the abilities of autograft, allograft/autologous red marrow and bBMP/collagen of promoting ingrowth of bone in a gaped interface of bone/implant, 18 rabbits were used and randomly divided into 2 groups. Specimens were harvested at 2, 4, and 6 weeks. Undecalcified sections were examined with fluorescent microscopy, microradioscopy and analyzed with computer. The results implied: bone ingrowth occurred in all groups except in control group after 6 weeks. The percentage of porous layer occupied by bone in defects was statistically higher in BMP/Col specimens of 4 weeks (P < 0.05). There was no significant difference among the three experimental groups 6 weeks after implantation. PMID- 1306794 TI - [Prevention and treatment of complications after portoazygous disconnection for portal hypertension]. AB - From 1978 to 1990, 35 complications were encountered in 203 cases of portoazygous disconnection in our hospital including intra-abdominal hemorrhage, AHF, ARF, ARDS, and gastric or pancreatic fistulae. The mortality rate was 8% with Hassab's operation, and 38% with Sugiura's, respectively. Emergency operation carried with a mortality of 31.1%, Whereas selective operation only 2.5%. 3.2% of all cases in Child's A group succumbed Postoperatively and 62% in Child's C group. The authors discussed the causes of the complications and ways to prevent them. PMID- 1306795 TI - [Selective vagotomy plus antrectomy and Roux-en-Y gastrojejunostomy in the treatment of duodenal ulcer]. AB - From 1982 to October 1990, 284 patients with duodenal ulcer were surgically treated. Partial gastrectomy and Billroth anastomosis (PGB) were performed in 92 patients, selective vagotomy plus antrectomy and Billroth anastomosis (VAB) in 92, and selective vagotomy plus antrectomy and Roux-en-Y gastrojejunostomy (VARY) in 98. Follow-up showed that VARY was superior in many respects to PGB and VAB such as in decreasing gastric acidity, long-term complications and Visick grading of I and II (P < 0.05). We conclude that VARY can be used in the treatment of duodenal ulcer. PMID- 1306797 TI - [Surgical treatment of corrected transposition of great arteries associated with intracardiac anomalies]. AB - From Nov. 1981, to Oct. 1990, 43 patients with corrected transposition of great arteries associated with intracardiac anomalies were operated on in our institute. There were 35 cases with type SLL, and 8 cases with IDD. However, 37 cases were associated with ventricular septal detect (VSD) and pulmonary stenosis (PS) or pulmonary atresia, 2 cases VSD, 2 cases PS, 1 case atrial septal detect and 1 case preexcitation tachycardia. The operative mortality rate was 9.3%. The operative experience demonstrates that for cases with type SLL corrected transposition of great arteries associated with VSD and (or) PS, satisfactory results can be achieved by repairing VSD via right atrium and mitral valve, and as far as pulmonary stenosis is concerned, pulmonary valvotomy or connection of left ventricle and pulmonary artery by using valved conduit can be adopted. PMID- 1306796 TI - [The release of vasoactive intestinal peptide in patients with dumping syndrome and its clinical significance]. AB - Plasma vasoactive intestinal peptide (VIP), blood glucose concentration and hematocrit (HCT) were measured in 15 patients after Billroth-II subtotal gastrectomy (B-II SG) and 8 healthy controls before and after oral glucose ingestion. In B-II SG group the rate of rise of VIP concentration was in positive correlation to the rate of rise of HCT (r = 0.501 P < 0.05) and to that of blood glucose (r = 0.715 P < 0.01). Also, the elevation rate of HCT blood glucose and VIP concentration was significant higher in B-II SG group than in controls (P < 0.05). It was found that the elevation rate of VIP concentration was much higher in patients with dumping syndrome after B-II SG than those without (P < 0.05). The results suggest that VIP may play a role in the pathogenesis of dumping syndrome. PMID- 1306798 TI - [Autogenous bronchial pedicle flap for tracheoplastic procedures]. AB - Nine cases of large tracheal defect due to resection of tumor or scar were repaired by using autogenous bronchial pedicle flap. The symptoms of airway obstruction rapidly disappeared after operation. The normal part of the right main bronchus and bronchus intermediate was used as material for repair, both lower and middle lobes were preserved in one case, and the lower lobe was preserved in another. We believe that in tracheoplasty with autogenous bronchial flap for large tracheal defect is satisfactory. PMID- 1306799 TI - [Microvascular anastomosis in replantation of 6 avulsed scalps]. AB - From 1990 to 1991, 6 avulsed scalps (total avulsing in 5, partial avulsing in 1) were replanted successfully. Follow-up for over 6 months showed that the hair of the replanted scalps grew normally in all the 6 patients. We think that the key to successful replantation is to anastomose the vessels effectively. The scalp can survive just with its superficial temporal vessels on both sides and with an artery-vein ratio of 1:1. The management of postoperative complications is discussed. PMID- 1306800 TI - [Changes of protein turnover in perioperative patients and effect of recombinant human growth hormone]. AB - 15N-Glycine constant infusion method was applied to study the changes of protein metabolism after major abdominal operation and the influence of recombinant human growth hormone (GH). Our results showed: (1) under the support of total parenteral nutrition (30 cal/kg/d and 1.25 g protein/kg/d), the protein turnover rate (Q), synthetic rate (S) and catabolic rate (C) all increased significantly (P < 0.05) with an outstriping increase of C over S on postoperative day 3 in comparison with that on preoperative day 3; (2) with the support of hypocaloric parenteral nutrition (20 cal/kg/d and 1.00 g protein/kg/d), Q, C values also increased significantly (P < 0.05) comparing with that of the control group on post operative day 7 in patients treated with one week GH (0.15 iu/kg/d), but S value increased more significantly (P < 0.01), which indicated that the postoperative use of TPN plus GH is much better than giving TPN alone. PMID- 1306801 TI - Enantiomers: implications and complications in developmental pharmacology. AB - The majority of synthetic drugs with chiral centers are administered as racemates. Thus chemically, and to an even greater extent biologically, a racemic drug is not a single compound, but a 50:50 mixture of two enantiomeric drugs. No generalization can be made concerning whether and to what extent the activity, in either qualitative or quantitative terms, differs between enantiomers. It is not unusual for the enantiomers of a drug to have a high degree of enantioselectivity for one action but no enantioselectivity for another action. For instance S propranolol is at least two orders of magnitude more potent than R-propranolol with regard to beta-adrenoceptor antagonism. However, the two enantiomers are equipotent with regard to their membrane stabilizing effect. It is often overlooked that enantioselectivity in the activity of enantiomers as determined in vitro cannot be extrapolated to the in vivo situation since enantioselective drug disposition can lead to an enantiomer ratio in vivo which differs substantially from that in the dosage form administered. Enantioselectivity in drug disposition seems to be the rule rather than the exception and, depending on whether the active or less active enantiomer is preferentially affected, there may be amplification or attenuation of in vivo as compared to the in vitro drug potency. PMID- 1306802 TI - Expression and release of neuroregulators during development: monoamines and neuropeptides. AB - The turnover of catecholamines (CA) was determined in the adrenal medulla and brain of rat fetuses and pups. In general we found a considerable increase soon after birth. The expression of mRNA for CA-synthesizing enzymes was also considerably enhanced in the adrenals shortly after birth. Furthermore, we demonstrated increased expression of neuropeptides after birth, increased synthesis of mRNA encoding for neuropeptide Y in the adrenals 24 h after birth; and considerable activation of the substance P gene in a respiratory nuclei of rabbit pups which had been breathing for 2 h as compared with fetuses at term. PMID- 1306803 TI - Hypoxic-ischemic damage in the neonatal brain: excitatory amino acids. AB - Perinatal brain damage is a major clinical problem. Recent studies suggest that excitatory amino acids (EAAs) may be important for the development of hypoxic ischemic brain injury in the newborn. Experimental work demonstrates that the immature brain is hypersensitive to the toxic effects EAA ('excitotoxicity'), hypoxic-ischemia is accompanied by an extracellular overflow of EAAs and hypoxic ischemic brain damage is reduced by EAA receptor antagonists. Clinical investigations demonstrate the presence of EAA receptors in vulnerable areas of the newborn human brain and the concentrations of EAAs in the cerebrospinal fluid are higher in asphyxiated than in control infants. Clinical studies are warranted to evaluate the importance of excitotoxicity for development of brain lesions after severe asphyxia. PMID- 1306804 TI - Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies. AB - Dextromethorphan undergoes O-demethylation to dextrorphan and N-demethylation to 3-methoxymorphinan. 3-Hydroxymorphinan, a didemethylated compound, is secondarily formed. The O-demethylation pathway to dextrorphan is polymorphic and under CYP2D6 genetic control. Adult and fetal studies were performed to characterize the cytochrome P450 families involved in dextromethorphan metabolism and their ontogeny. In adult volunteers in vivo and in vitro studies demonstrate that the O demethylation pathway to dextrorphan is dependent on CYP2D6 and is predominant in extensive metabolizers and defective in poor metabolizers of the drug. The N demethylation pathway to 3-methoxymorphinan is accessory and is dependent on the CYP3A subfamily. In human fetal microsomes, CYP2D6 protein and activity are not detectable until birth, while CYP2D6 RNA is present in significant amounts before birth. CYP3A activity is detectable in large amounts as early as the 17th week of gestation. Fetal and adult members of the CYP3A subfamily have close, although different, properties, as demonstrated by immunoinhibition studies. PMID- 1306805 TI - Treatment of growth failure in renal disease with recombinant human growth hormone: 2 years' experience. PMID- 1306806 TI - Studies on developmental neurology in the human fetus. AB - The development of the motor component of the embryonic and fetal central nervous system can be studied by observation of fetal movements, using real-time ultrasound. In this paper data on emergence and development of fetal movement patterns and behavioural states are reviewed in the light of the normal development of the nervous system, identification of disturbances in normal development and testing behavioural teratogenicity in the human. PMID- 1306807 TI - Thrombocyte monoamine oxidase activity and behavior deviances in adolescence. AB - The frequencies of patients with low thrombocyte monoamine oxidase (MAO) activity (defined as having an activity lower than 1 SD below the mean of a respective control group) were studied in 100 consecutive cases admitted to a clinic for child and youth psychiatry. 41 boys and 26 girls (group I) had behavior disorders, attention deficit disorders and/or alcohol and hashish abuse according to DSM III R. 16 boys and 17 girls had other diagnoses (group II). None of the 2 male patient groups differed significantly from the controls. A significantly higher percentage of the girls in group I had low activity of platelet MAO than in the control group (p = 0.015), while the girls in group II did not differ from the controls. Acting out, antisocial behavior and abuse is less accepted in women than in men. Therefore, the girls in the present study might be either more psychiatrically disturbed or have more deviant personalities than the boys, which might explain why our hypothesis about a lower thrombocyte MAO activity in the adolescents with externalizing symptoms (group I) was verified only in the girls. PMID- 1306808 TI - Developmental aspects of the monoamine-degrading enzyme monoamine oxidase. AB - In the rat heart, monoamine oxidase (MAO)-B activity was shown to predominate in 2- to 3-week-old animals, whereas MAO-A activity was reported to be very low in newborn rats and to increase considerably with age until it predominates. These results are in contrast with those found in the mouse heart, where an age dependent increase in MAO-B activity with no changes in 5-hydroxytryptamine deaminating activity was found to occur. There is evidence that the adult values of MAO activity are reached early in development in rat kidney and liver. In the rat lung the adult values of MAO-A activity are reached by day 40, whereas MAO-B activity is still increasing by day 80. Important differences have been reported in the developmental pattern of the two forms of MAO in the rat and mouse brain, with a decrease in the MAO-A/MAO-B ratio during postnatal development. In the human brain, the ontogenetic development of MAO-A and MAO-B appears to parallel that observed in the rodent brain. It is worth noting that most of the available data have to be considered with reservation owing to many methodological problems. Further studies are clearly needed to get reliable information on the ontogenesis of MAO in mammalian tissues. PMID- 1306809 TI - Functional changes implicating dopaminergic systems following perinatal treatments. AB - A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6 hydroxydopamine (6-OHDA) (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound, or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphetamine-induced activity. It was shown that prenatal metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d amphetamine-induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded according to the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine-induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85% depletion compared to control values) caused notable impairments. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered. PMID- 1306810 TI - Priming as a model of behavioural sensitization. AB - Repeated exposure to drugs acting as direct or indirect stimulants of central dopamine transmission results in sensitization to their behavioural stimulant properties (behavioural sensitization). Priming provides a simple model of behavioural sensitization particularly suitable for studies of its neural and molecular mechanisms. The results obtained to date indicate that priming results in an increased responsiveness of postsynaptic dopamine receptor mechanisms in the caudate nucleus, possibly due to an increased affinity of the D-1 receptor for its agonist. PMID- 1306811 TI - Biological markers of intrauterine exposure to cocaine and cigarette smoking. AB - We describe hair tests for assessment of fetal exposure to cocaine and cigarette smoking. Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolite benzoylecgonine, has been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the regularly used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation. To date, no biological markers have been identified that can predict the extent of fetal exposure to the adverse effects of toxic constituents of cigarette smoke. We measured maternal and fetal hair concentrations of nicotine and cotinine in mother-infant pairs. Smoking mothers had a mean of 21.3 +/- 18 ng/mg hair nicotine and 6 +/- 9.2 ng/mg of cotinine, significantly more than nonsmokers (0.9 +/- 0.8 ng/mg nicotine and 0.3 +/- 0.5 ng/mg cotinine, p < 0.0001). Babies of smokers had a mean nicotine concentration of 6 +/- 9.2 ng/mg (range 0-27.3) and cotinine of 2.1 +/- 3.7 ng/mg (range 0-12.2), significantly more than babies of nonsmokers (nicotine 0.6 +/- 0.7 ng/mg and cotinine 0.2 +/- 0.5 ng/mg; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306812 TI - [Salt and hypertension]. PMID- 1306813 TI - [Mutualization and controversy viewpoints on X syndrome]. PMID- 1306814 TI - [Systolic hypertension in the elderly: Chinese trial (syst-China). Interim report]. AB - Two thousand and seventy-one elderly isolated systolic hypertensive patients entered the multicenter, randomized, double-blind, placebo-controlled clinical trial (997 in the active treatment group and 1,074 in the placebo). The differences of age, height, weight, sex constituent and baseline blood pressure between active treatment and placebo groups yielded no significances. In the 30 month follow-up period, the systolic and diastolic blood pressure in the active treatment were lower than the placebo group (P < 0.05) since the third month of the trial; the side effects were mild and the compliance of the participants was good (97% of the participants in the active treatment was taking medicine punctually during follow-up period; and 96% of the participants in the placebo group did so as well). The average morbidity of isolated systolic hypertension in our country was 8.10%, and the morbidity in female was higher than that in male, based upon the results of our trial. The present trial is in progress and the final results will not be reported until the end of the trial. PMID- 1306815 TI - [The effects of nitrendipine on the quality of life in the elderly patients with isolated systolic hypertension (ISH)]. AB - By case-control study, we investigated the effects of nitrendipine on the quality of life in 100 patients who were participating in Chinese Trial of randomized double-blind systolic hypertension in the elderly. The results showed that the patients group had lower scores of quality of life than the matched normotensives (P < 0.05-P < 0.01). After 40-week treatment period, the active treatment group (45 patients) had satisfied blood-pressure control and improved physical symptoms. As compared with the active group, however, the control group (42 patients) scored significantly higher on physical symptoms (P < 0.05-P < 0.01), fewer on memory, vatality, vision, well-being and social activity (P < 0.05-P < 0.01). Our findings show that nitrendipine had some positive effects on the quality of life in the elderly patients with isolated systolic hypertension (ISH) and these can be meaningfully assessed with available psychosocial measures. PMID- 1306816 TI - [Circadian blood pressure rhythm and its characterization in isolated systolic hypertension (ISH)]. AB - Twenty-four-hour noninvasive ambulatory blood pressure (ABP) was performed in 131 consecutive elderly subjects (61 with isolated systolic hypertension, ISH; 19 with mixed/diastolic hypertension, MDH; 29 with borderline hypertension, BLH; 23 in the normotensive group, NT). It was found that in ISH blood pressure rised during awaking period and fell during sleeping period (P < 0.05); the circadian systolic blood pressure rhythm was similar to ones in MDH, BLH and NT. However, the circadian diastolic blood pressure rhythm was attenuated in ISH. We conclude that circadian blood pressure rhythm alters in ISH, which may be related to the ischemia in organs, especially cerebral ischemia. PMID- 1306817 TI - [A prospective study on the effect of nifedipine of the cardiovascular complications in the elderly hypertensives]. AB - The purpose of this single-blind, placebo-controlled trial was to assess whether long-term treatment with nifedipine can have a beneficial preventive effect on the cardiovascular complications in the elderly hypertensives. Randomization took place in 11 clinical centers between July 1987 and June 1988, and involved 1,666 patients, 60-70 years of age. 912 participants were assigned to nifedipine (N group) and 754 to placebo (P group). Follow-up time for each participant was taken as the time from randomization to either the study events or June 1990, with an average of 30 months (27-36 months). The results showed that the cumulative rates for all cardiovascular study events in the N group were significantly lower than that in the P group at 18 months (chi 2 = 5.278, P < 0.05), and the cumulative rates for stroke in the N group was significantly decreased at 24 months (chi 2 = 4.612, P < 0.05), at 27 months, 16.00% and 36.91% (chi 2 = 5.080, P < 0.05), respectively for the N and the P groups. The incidence of stroke in the N group was decreased by 57% within 2.5 years, but cardiac events were not significantly lowered (14%, P > 0.05) in comparison with the P group. The benefits of treatment in the trial seemed to depend on age at entry and were more obvious in male than in female patients. PMID- 1306818 TI - [A correlative study on control of hypertension and onset of stroke and myocardial infarction]. PMID- 1306819 TI - [The changes in circulating platelet-derived growth factor and tumor necrosis factor in hypertensive patients]. PMID- 1306820 TI - [The effect of captopril on sugar metabolism in hypertensive patients]. PMID- 1306821 TI - [X syndrome--report of six cases]. AB - Six patients (2 males and 4 females, mean age of 46 years) with X syndrome were reported in this paper. All patients presented with typical exertional angina pectoris. In 4 patients the angina had a variable threshold of onset, it often occurred at rest and occasionally nocturnally. The electrocardiogram during chest pain showed ST segment depression of more than 0.05-0.1 mV in all 6 patients. The treadmill or bicycle ergometer exercise test was positive in 4 cases (ST segment depression > 0.1 mV), equivocal in 1 (ST segment < 0.1 mV) in whom the 201Tl exercise myocardial perfusion scan showed sign of ischemia, and negative in 1 in whom atrial pacing at heart rate of 135 beats/min induced angina and ST segment depression of 0.1-0.15 mV. Echocardiograms and X ray chest films revealed no sign of ventricular hypertrophy or enlargement. The 201Tl exercise myocardial perfusion scan was performed in 5 patients, which showed signs of ischemia in 4 patients and suspected to have ischemia in 1. Left ventriculograms and coronary angiograms were normal in all 6 patients. Ergonovine provoking test (total dose of 0.4 mg) was negative in 5 patients, it was not performed in 1 in whom there was no evidence of coronary artery spasm by angiogram during appearance of electrocardiographic ischemic changes and chest pain. Left ventricular endomyocardial biopsy was performed in 1 patient, which showed significant smooth muscle cell proliferation in the medial layer of a small artery with diameter of 62.5 mu which produced narrowing of the lumen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306822 TI - [Surgical treatment of atrioventricular septal defect]. AB - From April 1975 through November 1990, 184 patients with atrioventricular canal malformation defect were operated in our institute. Among them, 151 cases were partial form and 33 cases were complete form (including 7 cases associated with tetralogy of Fallot). Total mortality rate was 6.5%. 164 cases had been followed up for 3 months to 15 years. The results showed that 135 cases were in heart function of class I and 29 were in class II. To improve the results of surgical treatment of this cardiac anomaly, we consider the following points important: (1) Pathological anatomy of atrioventricular septal defect must be studied carefully. (2) The method of operation must be improved, including repairing ASD and VSD without damaging the conduction system and obstruction of the outlet of left ventricle, and without insufficiency of mitral valve as well. (3) Operation must be performed strictly according to the indications. (4) More attention must be given to the perioperative management. PMID- 1306823 TI - [Surgical treatment of mitral prolapse with chordae plasty]. AB - Surgical treatment of 8 cases of anterior mitral leaflet prolapse was reported. Of the 8 cases, chordae elongation was occurred in 2, chordae rupture in 6, and congenital in 6, rheumatic in 2. Chordae reimplanting was performed in 5 cases, chordae shortening in 2, chordae prosthesis with surgical suture in 1, and combined annuloplasty in 7 of the 8 cases. The result of mitral plasty was better in congenital mitral prolapse. Indications of this technique and postoperative management were listed. PMID- 1306824 TI - [Evaluating active rheumatism with biopsy of the ventricular myocardium]. AB - Endomyocardial biopsy (EMB) specimens obtained from ventricles in 10 patients with rheumatic heart disease were examined under light microscope. The results showed that typical Aschoff bodies and Anitschkow cells were found in 5 cases and Anitschkow cells only in other 2 cases. The positive detecting rate of active rheumatic lesion was 70 per cent. Active rheumatism was suggested clinically in 4 out of 7 cases with positive rheumatic lesions, whereas no clinical active rheumatism was suggested in the remaining three. The present study indicates that the active rheumatism lesions are frequently present in patients with rheumatic heart disease. Among the 3 cases without active rheumatic lesions, clinical active rheumatism was suggested in one, but no active clinical rheumatic evidence in the remaining two. In conclusion, the EMB technique gives limited value in assessing clinical active rheumatism in patients with rheumatic heart disease. PMID- 1306825 TI - [Exploration of pacing treatment in sick sinus syndrome]. PMID- 1306826 TI - [Clinical evaluation of predicting sudden death in idiopathic dilated cardiomyopathy with ventricular late potential]. PMID- 1306827 TI - [Clinical value of QT and its variance]. PMID- 1306828 TI - [Q-Tc changes during ergometric exercise stress test in patients with coronary artery disease]. PMID- 1306829 TI - [A comparative study on the dosage and infusion rate of urokinase during intravenous thrombolysis]. PMID- 1306830 TI - [A study of the antiarrhythmic mechanism of berberine on delayed activation potassium current by voltage clamp]. AB - The effects of berberine (0.1-10 mg/L) on delayed activation potassium current (iK) of canine Purkinje fibers were studied with two-microelectrode voltage clamp technique. Berberine (Ber) significantly reduced the amplitude of iK in concentration-dependent manner. When perfused with 10 mg/L Ber, the amplitude of tail current of the Purkinje fibers decreased immediately and the inhibition rate was 73.6 +/- 4.5% (n = 9, P < 0.001). The inhibition effect of berberine on iK may explain its prolongation effect on action potential duration and its antiarrhythmic action. PMID- 1306831 TI - [Effect of endogenous estrogen on plasma high density lipoprotein and total hydrosulfuryl group in membrane of erythrocyte in cholesterol-fed rats]. AB - Under a cholesterol load, the effects of endogenous estrogen on plasma high density lipoprotein cholesterol (HDL-C), total hydrosulfuryl (T-SH) group in the membrane of erythrocyte and plasma total cholesterol were observed in female rats with a ovariectomized control group. The results indicate that endogenous estrogen might prevent the rats of atherosclerosis formation by keeping plasma HDL at higher level and increasing in T-SH group in the membrane of erythrocyte, and preventing the increase in total plasma cholesterol. PMID- 1306833 TI - Electrosurgery in restorative Dentistry: 2. Clinical applications. AB - Electrosurgery techniques have been used in dentistry as an aid to soft tissue management for nearly 60 years. However, it was not until the late 1960s that the principles of electrosurgery were understood and improved equipment became available. Part 1 of the two-part series covered the theory behind using this technique. Part 2 will now discusses the clinical applications. PMID- 1306832 TI - [Noninvasive estimation of left ventricular relaxation time constant by continuous wave Doppler echocardiography]. AB - In order to develop a new method for estimating left ventricular relaxation time constant (T)noninvasively, continuous wave Doppler echocardiography (CWD) and left heart catheterization (Cath) were performed simultaneously in 25 patients with mitral regurgitation (MR). The MR velocities were recorded by CWD and digitized every 20 ms along the descending limb of the Doppler spectra to obtain the peak rate of decline of pressure gradient (-dPG/dt max) and the instantaneous left ventricular pressure (PO) at the time point of -dPG/dt max. T was then calculated as: T = PO/-dPG/dt max, and compared with T measured from pressure curves by Weiss's method. The result showed that there was a high correlation of T determined by the two techniques (r = 0.94, SEE = 4.36 ms) and there was no significant difference between the two methods. Thus, CWD offers a new and reliable approach to the noninvasive estimation of T in patients with MR. PMID- 1306834 TI - Prosthetic practice in the National Health Service: 1. Complete dentures. AB - This two part series on the making of dentures in the National Health Service includes useful practical advice for the general practitioner. Part 1 discusses complete dentures, whilst part 2 will cover partial dentures. PMID- 1306835 TI - Clinical aspects of occlusion: 2. The reorganized approach. AB - This is the second of two articles which aims to familiarize the reader with essential occlusal principles and terminology and to give some guidelines as to which cases are suitable for crown and bridgework. The first article covered occlusal terminology and the conformative approach to crown and bridgework, the second describes the reorganized approach. In both articles, there are illustrated, clinical cases which demonstrate and overcome some of the occlusal problems encountered. PMID- 1306836 TI - The use of visible light cured periodontal dressing after surgical exposure of palatal canines. AB - A technique is described which utilizes a light-cured periodontal dressing (Barricaid) in conjunction with the surgical exposure of palatally displaced maxillary canines. The procedure is very quick and simple to perform, with some distinct advantages over alternative methods. PMID- 1306837 TI - Stress and the dental team: a qualitative investigation of the causes of stress in general dental practice. AB - Working closely together in a general dental practice can cause many stresses and inter-personal problems. Results are presented of discussions with groups of dental practitioners, their hygienists and dental surgery assistants, indicating stressors and complaints most common in each group. PMID- 1306838 TI - Stress and the immune system. AB - The centuries-old belief that stressed individuals are more susceptible to disease has gained scientific respectability in recent years. A new interdisciplinary science, psychoneuroimmunology (or as it is now more appropriately named, psychoneuroendocrinimmunology) has been born and, judging from the number of articles appearing annually, is thriving. In essence, stressors activate the neuroendocrine axis, which in turn influences the immune system. This is a bidirectional process, since chemicals are released by activated immunological cells which alter the functioning of the endocrine and autocrine nervous systems and influence our behaviour. This article examines these interactions. PMID- 1306839 TI - Atopic eczema and orthodontic headgear. AB - A case is reported where cutaneous irritation by orthodontic headgear was followed by a localized exacerbation of atopic eczema. It is suggested that care should be exercised when considering fitting such an appliance in an individual who suffers from atopic eczema. PMID- 1306840 TI - Molecular biology of disorders of sex differentiation. AB - Sexual ambiguity can be a difficult and sometimes confusing diagnostic problem in children. Recent developments in molecular biology have provided the opportunity to analyze the gene responsible for testicular determination, SRY, the androgen receptor gene and the gene encoding the cP450 enzyme specific for 21 hydroxylation, CYP21B, whose defects are responsible for congenital adrenal hyperplasia. Southern-blotting studies and PCR analyses of SRY, androgen receptor and CYP21B genes can be routinely used for the direct diagnosis of gonadal dysgenesis, androgen insensitivity syndromes and congenital adrenal hyperplasia, respectively. In sex-reversed XY females, several de novo mutations or deletions in the SRY gene have been reported. Defects in the human androgen receptor cause a spectrum of defects in male phenotypic sexual development associated with abnormalities in the receptor protein. Analyses of the androgen receptor gene structure have identified the causative mutation in some families: mutations that result in large-scale alterations of the structure of the androgen receptor, mRNA or gene mutations that alter the primary structure of the androgen receptor protein and mutations that alter the level of mRNA. The diversity of clinical phenotypes, apparent in 21-hydroxylase deficiency, is paralleled by a considerable degree of mutational heterogeneity in the CYP21 gene locus. Various changes causing severe 21-hydroxylase deficiency have been reported: point mutations, gene conversions and gene deletions. In conclusion, substantial progress has been made elucidating genetic defects causing sex reversal in XY females, the androgen insensitivity syndrome and congenital adrenal hyperplasia. Molecular genetics can also be applied for carrier identification and prenatal diagnosis. PMID- 1306841 TI - Prevalence of autoantibodies to endocrine organs in girls with Ullrich-Turner syndrome aged 5-14 years. AB - Endocrine function tests and a broad panel of autoantibodies to endocrine organs were assessed in 77 patients aged 5-14 years with Ullrich-Turner syndrome (UTS), who were included in the German UTS Multicenter Study. None of these patients had abnormal pituitary, thyroid or adrenocortical function, as assessed by the adequate hormone tests. Antibodies to thyroid microsomes were found in 3 of the 77 (3.9%), antibodies to thyroglobulin in 0/77, antibodies to adrenocortical cells in 1/77 (1.3%), gastric parietal cell antibodies in 2/77 (2.6%), and anterior pituitary cell antibodies in 3/77 (3.9%) probands. These prevalences were not significantly higher than those obtained in 154 age- and sex-matched normal control children when 2 control subjects were assigned to each patient with UTS. Our data do not show an increase in serological signs of endocrine autoimmunity in young patients with UTS suggesting that a putative association of these syndromes does not exist from birth and is not usually present in childhood. However, we cannot exclude the possibility that UTS is associated with factors that render these patients more susceptible to endocrine autoimmunity later in life. PMID- 1306842 TI - GH assessment and three years' hGH therapy in girls with Turner syndrome. AB - Fifteen girls with Turner syndrome (TS) were submitted to GH secretion assessment before undergoing hGH therapy. In the first 9 months, hGH was given at a dose of 0.5 IU/kg/week s.c. daily; afterward, the dose was increased to 1 IU/kg/week s.c. daily. The girls were prepubertal, with a mean (SD) chronological age (CA) of 12.5 (2.6) years, and a mean (SD) bone age of 10.5 (1.8) years. A clonidine stimulation test, 1-29 GHRH test and GH spontaneous nocturnal secretion assessment were performed in all patients. Results showed a variable pattern of GH secretion in 10 patients, in only 2 did we find all values definitely normal, and in 3 we found a total GH deficiency. Height velocity, expressed as standard deviation scores (SDS) for CA according to Turner references, during the first year of treatment increased significantly: 0.36 (1.15) -3.30 (2.87) (p < 0.001), and the increment remained quite unchanged during both the second and third years: 3.16 (2.96) and 2.55 (3.87), respectively (n.s.). Height, expressed in SDS for CA for Turner references, increased significantly throughout the whole period of treatment and reached the highest value at the end of the third year of therapy. GH secretion parameters poorly correlated with pretreatment auxological data or response to treatment. Our long-term study confirms that in TS GH measurement is not useful in indicating hGH therapy or in predicting the response. PMID- 1306844 TI - Pulsatility of growth hormone secretion and its relation to growth. AB - 84 short children were submitted to nocturnal spontaneous growth hormone (GH) secretion tests and to provocative insulin-arginine tests. Discrepancies between the GH peak under the provocative test (I-AP) and nocturnal GH maximal peak (PA) and mean concentration (MC) were frequently observed, despite significant statistical correlation between I-AP and PA (r = 0.47; p < 0.02) and between I-AP and MC (r = 0.42; p < 0.02). Night profiles were evaluated by time analysis: 31 fitted a theoretical model, consisting of a cosine function of time (modelizable profiles). Spectral analysis, from Fourier transformation, indicated predominant periods after cluster analysis. The major predominant period in modelizable (n = 9) and in nonmodelizable (n = 28) profiles was close to 180 min and a secondary period was on average 122 min in modelizable (n = 20) and 105 min in nonmodelizable (n = 23) profiles. Two modelizable and two nonmodelizable profiles escaped this classification. The general, auxological and GH secretory status did not differ significantly between patients with modelizable and nonmodelizable profils. Growth velocity correlated with GH mean concentration (r = 0.36; p < 0.001), but not with plasma insulin-like growth factor-I levels nor with any of the pulsatility indices: number of peaks, main period, and pulse height index = mean GH peak/mean GH concentration. The relevance of GH pulsatility to growth is, therefore, unclear in humans. PMID- 1306843 TI - Comparison of four computerized models to estimate 24-hour growth hormone secretion in girls with Turner's syndrome. AB - Daily pituitary growth hormone (GH) secretion can be estimated from a 24-hour GH profile by various methods. We have used four methods to assess GH secretion in 36 girls with Turner's syndrome: the method described by Thompson et al., the Pulsar algorithm combined with the method of Hellman et al. and two deconvolution techniques. The number of detected peaks varied considerably among the methods. The mean (+/- SD) total daily secretion per square meter body surface was 0.53 (0.19) U/m2.day by deconvolution, in contrast to 0.31 (0.17) with the Hellman method and 1.06 (0.37) according to Thompson. The differences are explained by different assumptions about the metabolic clearance rate and various methodological aspects. Assuming a degradation rate of 50%, the growth hormone substitution dosage would be 1-2 IU/m2.day in GH-deficient children. The usual dosage in girls with Turner's syndrome is expected to lead to serum GH levels approximately 4 times higher than in the untreated state. PMID- 1306845 TI - The capacity to increase GH secretion at puberty reflects the severity of GH deficiency. AB - This study evaluates the effect of the spontaneous pubertal increase in sex steroids on GH secretion in GH-deficient patients. Fifteen patients (10 boys, 5 girls) with idiopathic isolated GH deficiency diagnosed before puberty (GH peak < 8 micrograms/l after 2 arginine insulin stimulation tests) were reevaluated for their GH secretion using the same test after completion of their hGH therapy and puberty. Their ages at diagnosis and at the last evaluation were 8.2 +/- 0.7 (SE) (range 4.9-14.9) and 17.8 +/- 0.3 years (15-23), respectively. The data at diagnosis and at last evaluation showed that (1) the mean height increased from 4 +/- 0.3 to -2.5 +/- 0.3 SD (p < 0.01), (2) the mean GH peak increased from 4.4 +/- 0.3 (1.6-8) to 7.6 +/- 0.8 micrograms/l (2-13.2, p < 0.01); at the last evaluation, 8/15 patients had GH peak > 8 micrograms/l and (3) the mean plasma insulin-like growth factor I increased from 0.28 +/- 0.05 to 0.42 +/- 0.03 U/ml (n = 6, p < 0.05). The mean increase in the GH peak was 3.2 micrograms/l (-3 to 10.6). It was negatively correlated with the degree of growth retardation at diagnosis (r = -0.74, p < 0.005). We conclude that the increase in the GH peak at puberty in patients with GH deficiency reflects the severity of GH deficiency and that a corrective factor of the cutoff number is necessary for the diagnosis of GH deficiency in puberty. PMID- 1306846 TI - Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure. AB - Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306847 TI - Relationship between resting metabolism and hepatic metabolism: effect of hypothyroidism and 24 hours fasting. AB - In this paper, we have examined the relationship between the changes in the resting metabolic rate (RMR) and the changes in hepatic metabolism induced by hypothyroidism and 24 h fasting. The results show that hypothyroidism induces a significant decrease in RMR, while 24 h fasting reduces RMR in euthyroid but not in hypothyroid rats. We have also measured oxygen consumption in isolated hepatocytes from euthyroid and hypothyroid rats, fed or fasted for 24 h. The results show that hypothyroidism is characterized by reduced hepatic oxygen consumption. On the other hand, 24 h fasting induces an increase in oxygen consumption in both euthyroid and hypothyroid rat liver cells, although the respiratory rates of hypothyroid rats were lower than those of euthyroid rats. The above findings, as a whole, show that hypothyroidism and 24 h fasting have similar effects on RMR but opposite effects on hepatic metabolism. In addition, a normal thyroid state does not appear to be necessary for the observed changes in hepatic metabolism due to 24 h fasting. PMID- 1306848 TI - Effects of tartrate thyrotropin-releasing hormone treatment on serum thyrotropin, free triiodothyronine, free thyroxine and prolactin levels in patients with spinocerebellar degeneration. AB - The aim of the present study was to investigate the pituitary-thyroid axis function during the long-term (30 days) intramuscular administration of 4 mg/day of thyrotropin-releasing hormone tartrate (TRH-T) in 15 patients with spinocerebellar degeneration. The study was performed as follows: (1) acute 4 mg TRH-T test with hourly prolactin (PRL) and thyroid-stimulating hormone (TSH) level evaluations for 6 h; (2) placebo; and (3) 4 mg/day of TRH-T administration for 30 days with TSH, PRL, and free T3 and T4 (FT3 and FT4) levels evaluated on days 1, 15 and 30. Hormone determination was performed just before and 1 h after placebo or TRH-T administration. The acute administration of TRH-T caused a sustained rise of TSH which lasted until the 6th hour and of PRL which declined after 1 h (p < 0.01). During placebo administration, no change of TSH, PRL, FT3 or FT4 was observed. On the 1st day of treatment, 1 h after the TRH-T injection, a significant increase of both TSH and PRL levels occurred (p < 0.01). As compared to the 1st day, a significant decrease of the TSH (p < 0.01) levels occurred on the 15th and 30th days before TRH-T: the TSH response to TRH-T administration was present although less than on the 1st day (p < 0.01). Moreover, throughout the whole period of treatment, no difference was recorded for PRL levels before or after TRH-T administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306849 TI - Prolactin isoforms secreted by human prolactinomas. AB - Prolactin (hPRL) secreted by human prolactinoma cells in culture was purified by gel filtration, lectin affinity chromatography and gel electrophoresis in order to identify the different isoforms of the hormone and to test their respective immunoreactivities and bioactivities. The nonglycosylated hPRL (NG-hPRL), unbound to lectins, was the major form and was a species (NG1-hPRL), of 23,000 (M(r)) apparent molecular weight. The lectin-bound glycosylated hPRL (G-hPRL) consisted of three forms, G1-, G2- and G3-hPRL, of identical molecular weights (25,000 M(r)). Endoglycosidase treatment indicated that these three forms differed by the heterogeneity of their carbohydrate chains. These G-PRLs proved to be 68% less immunoreactive and 50% less bioactive than NG-hPRL. It is concluded from these data that, in prolactinomas, the main variant of the hormone is the nonglycosylated form of PRL. PMID- 1306850 TI - Reduced number and LH content of marginated secretory granules in pituitary gonadotropes of streptozocin-induced diabetic male rats. AB - The transport of secretory granules towards the subplasmalemmal (SPL) region of the luteinizing-hormone (LH) gonadotrope is controlled by the LH-releasing hormone-dependent pathway. The SPL granules contain the most readily releasable LH. To test the effect of diabetes on both the number and LH content of marginated granules, we studied by indirect immunogold-labelling pituitaries from control and streptozocin (STZ)-treated male rats. On electron micrographs we measured the areas of the gonadotrope nucleus and cytoplasm, counted all secretory granules, and counted and measured secretory granules in selected SPL regions. Furthermore, we counted gold particles (IG) on (a) the secretory granules of the SPL regions, (b) the intergranular SPL cytoplasm and (c) the region outside the cell. Finally, in order to evaluate possible diabetes-related changes of the pituicyte cytoskeleton, we measured by densitometry actin, tubulin, vimentin, and desmin in immunocytochemically stained pituitary sections. In diabetic compared with control cells of the studied pituitary region, we observed: (a) cytoplasmic atrophy; (b) the number of secretory granules per unit area increased in the total cytoplasm, and decreased in the SPL cytoplasm (lowered regulated secretion); (c) decreased IG labelling in the SPL granules (reduced amount of hormone transported by each granule towards the cell membrane); (d) decreased IG labelling in the integranular SPL cytoplasm (reduced constitutive secretion), and (e) strongly increased actin and desmin, yet unchanged tubulin and vimentin immunoreactivity. Our data indicate that both regulated and constitutive secretion are possibly reduced in gonadotropes of diabetic male rats. The cytoskeletal alterations may also contribute to the reduced regulated secretion. PMID- 1306851 TI - Serum concentrations of ethinylestradiol, 3-keto-desogestrel, SHBG, CBG and gonadotropins during treatment with a biphasic oral contraceptive containing desogestrel. AB - During a cross-over study, the pharmacokinetics of ethinylestradiol (EE) and 3 keto-desogestrel (KDG) were investigated on days 7 and 22 of one cycle of treatment with two biphasic formulations containing 50 micrograms EE (7 tablets) and 50 micrograms EE + 125 micrograms desogestrel (DG) (15 tablets) (50/50 EE) or 40 micrograms EE + 25 micrograms DG (7 tablets) and 30 micrograms EE + 125 micrograms DG (15 tablets) (40/30 EE). Peak serum levels and areas under the curve of EE increased significantly by 50% between days 7 and 22 of those taking 50/50 EE, while during treatment with 40/30 EE, no difference was found between days 7 and 22. Both formulations caused identical KDG levels on day 22. There were only slight differences in the effects of both preparations on sex-hormone binding globulin (SHBG; +150 to +160%) and on corticosteroid-binding globulin (CBG; +130 to +150%) on day 7. On day 22, the changes were more pronounced with 50/50 EE (SHBG, +310%; CBG, +240%) than with 40/30 EE (SHBG, +250%; CBG, +180%). On day 22 after discontinuation of treatment, the SHBG and CBG levels were still significantly above the control values. Using both formulations, LH and FSH levels were significantly suppressed on day 22, while on day 7 no significant reduction was observed. The rise in the EE levels between days 7 and 22 of 50/50 EE intake and the time course of the EE concentrations during treatment with 40/30 EE appear to be due to an inhibition of hepatic metabolism by the contraceptive steroids, as EE is nearly exclusively bound to albumin which does not change. PMID- 1306852 TI - Usefulness of CV 205-502 in a case of allergy to ergot-derived drugs. AB - This study reports a case of allergy to ergot-derived drugs in a patient with a prolactin (PRL)-secreting microadenoma. The anamnesis revealed allergic reactions to the administration of analgesics and antibiotics. The administration of dopamine agonist drugs, such as bromocriptine (BRC; 2.5 mg) or lisuride (0.2 mg), induced after a few minutes the appearance of nausea, vomiting, postural hypotension, headache, edema of the glottis with dispnea and acroedema. The edemas disappeared a few hours after the administration of antihistaminic drugs while nausea, vomiting, postural hypotension and headache persisted for a few days. Therefore, the patient was tested with another dopamine agonist non-ergot derived drug, quinagolide (CV 205-502), which did not cause side effects or allergic reactions. Furthermore, not only was the responsiveness to the drug optimal but it also normalized the PRL levels, and menses reappeared after more than a 5-year amenorrhea. This report suggests that ergot-derived drugs, such as lisuride and BRC, seldom induce allergic reactions apart from common side effects. Consequently, the feasibility of using a new drug with a different molecular structure (non-ergot derived) effective in the therapy of hyperprolactinemic syndromes represents a good alternative to conventional therapy. PMID- 1306854 TI - Strategies for effective appointment book control. PMID- 1306853 TI - Increasing the number of applicants to schools of dentistry. PMID- 1306855 TI - Taking dentistry to the airwaves: the idea becomes reality. PMID- 1306856 TI - Save money with ISDS' newest member benefit: the section 125 cafeteria plan. PMID- 1306857 TI - Some concerns of younger dentists. PMID- 1306858 TI - A comparison of leakage of filling materials in demineralized and non demineralized resected root ends under vacuum and non-vacuum conditions. AB - A study was conducted to compare the marginal apical leakage of root-end filling materials under vacuum and non-vacuum conditions, and to assess the effect of demineralization by application of citric acid to the root ends on the apical marginal leakage of root end filling materials. The root canals of 148 extracted human canines and premolars were handfiled and sealed with gutta-percha and Roth's 801 sealer using cold lateral condensation. The teeth were divided into 8 groups that received retrofilling materials. The materials tested were amalgam, IRM and gutta-percha/sealer with and without successive application of citric acid. Half of the specimens were placed under vacuum conditions in methylene blue dye, and the other half were placed in the dye for the same time period without exhausting air from the flask. The teeth were split longitudinally and the extent of dye penetration was determined with a stereomicroscope and eyepiece micrometer. The most evident difference in dye penetration was found between the positive control groups. Under vacuum conditions, the positive controls showed complete penetration of the unobturated canal system with dye. With passive immersion only partial penetration of the unobturated canal system occurred. Application of citric acid to the root end did not adversely affect the seal of amalgam, IRM or gutta-percha/sealer. PMID- 1306859 TI - Comparison of three imaging techniques for assessing endodontic working length. AB - The accuracy of endodontic working length estimation was investigated using three imaging techniques: radiography (Rd), Xeroradiography (Xr) and Radiovisiography (RVG positive and negative prints). An in-vitro model of extracted single straight roots, mounted in wooden blocks with wax, was employed in the study. Optimum exposures were established for each of the imaging techniques. The magnification of the images was measured and the resolution of the RVG images was also investigated. Comparable Rd (D-speed film), Xr,RVG positive and RVG negative images were made of five roots with size 10 files in situ. Images of 10 standard files were made, ranging from 2.0 mm through the root apex to 2.5 mm short of the apex, resulting in 200 images. Six observers each assessed the working distance on 100 images, measuring the distance from the apical foramen to the file tip. After allowing for the magnification of the images, these results were compared with the 'true' file tip to apical foramen (measured with the aid of a reflex microscope). The inaccuracy of working distance estimations was considered to be of clinical significance (> 0.5 mm) in 6% of measurements made from Rd and Xr, 19.2% of measurements from RVG negative and 32.3% from RVG positive images. In addition, 14% of RVG images were too poorly defined to be assessed. The first generation RVG system was used in this study. It was therefore concluded that the most accurate estimates of working distance were made from Xr and Rd images, and that RVG images, particularly the RVG positive images, were the least accurate and most difficult to read.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306860 TI - Scanning electron microscopic study of the apical dentine surfaces lased with ND:YAG laser following apicectomy and retrofill. AB - The purpose of this investigation was to study the effects of a Nd:YAG laser on the cut surface of teeth using scanning electron microscopy (SEM). Eighteen single-rooted teeth were cleaned, shaped, and obturated with gutta-percha and root canal sealer. The apical 3 mm of each tooth were resected with a diamond fissure bur, and the teeth were randomly divided into two groups of nine teeth each. The resected surface of each root in one group was lased twice. The duration of lasing and the number of pulses were recorded for each tooth. The teeth were air dried, mounted on stubs, sputter-coated with gold-palladium and examined under SEM. Application of the Nd:YAG laser caused melting of apical dentine surfaces. The melted material resembled the appearance of glazed interconnected droplets. Resolidification and recrystalization of the melted areas appeared to be incomplete and discontinuous. Some areas between the glazed regions appeared similar to those of non-lased apical dentine resected root surfaces. PMID- 1306861 TI - Effect of thermal placement techniques on some physical properties of gutta percha. AB - Some clinical techniques for the placement of gutta-percha root fillings involve the application of heat. This study was undertaken to assess the effects of intracanal heating techniques on the following properties of gutta-percha: coefficient of thermal expansion, softening temperature, phase transition temperature and organic content. Samples from each of four products were prepared by three different methods. The materials were studied by thermomechanical analysis, simultaneous thermogravimetry and differential thermal analysis, and by measurement of weight loss on ashing. It was shown that the techniques of gutta percha placement involving heating in the root canal caused reversible physical changes in the materials without any apparent change in chemical composition. The average coefficient of thermal expansion was 137 x 10(-6)/degrees C, the softening temperature was 55.5 degrees C, there were two characteristic phase changes, and the organic content was 25%. PMID- 1306862 TI - A comparison in vitro of two ultrasonic root canal preparation techniques. AB - Two ultrasonic techniques were compared for their ability to clean and shape root canals in extracted human teeth. One technique was recommended by the manufacturer (Cavi-Endo, Dentsply), while the other was a modification by the authors of the stepdown technique. Mesiobuccal root canals of molars were instrumented using these techniques, after which a silicone impression material was injected into the prepared canals. The roots were then split longitudinally and one half was stained for debris scoring while the silicone impressions were assessed for shape. The results showed that the modified technique produced significantly cleaner canals than the recommended technique. The shaping ability of both techniques was difficult to evaluate because of the complex morphology of molar root canals. The final shape of the prepared canal depended more on the initial shape than on the instrumentation technique. PMID- 1306863 TI - Clinical detection of the minor mesiobuccal canal of maxillary first molars. AB - One hundred extracted maxillary first molars from a South East Asian population were sectioned at a level below the roof of the pulp chamber. The detection of the minor mesiobuccal canal was determined on the pulpal floor using a size 08 file. When the canal was not detected by this technique, its presence or absence was then determined by sectioning the mesiobuccal root transversely, and the position of the extra canal was explored from the cut end. It was found that by modifying the outline of the access cavity, and by widening and deepening the groove running palatally from the major mesiobuccal canal up to a depth of 0.5 mm and a distance of 2.0 mm, the visibility of the extra mesiobuccal canal orifice was greatly improved. This study showed that more than 50% of maxillary first molars had a minor mesiobuccal canal, and 19% of these canals could not be detected clinically. PMID- 1306864 TI - Periradicular healing and apical closure of a non-vital tooth in the presence of bacterial contamination. AB - This case report addresses the periradicular tissue response and root-end closure of a maxillary central incisor in the presence of bacterial contamination. The implications for the control of bacteria through the use of calcium hydroxide and/or systemic antibiotic coverage are considered in the light of scientific evidence and clinical treatment. PMID- 1306865 TI - Intra-oral manifestation of neurofibromatosis: a case report. PMID- 1306866 TI - Mediastinal abscess and pneumonia of dental origin. PMID- 1306867 TI - Endodontic problems and failures: how to predict, evaluate and prevent many of them. PMID- 1306868 TI - Age-weighted profit sharing plans. PMID- 1306869 TI - Report of retirement funds of dentists age 55+. PMID- 1306870 TI - Dentistry during the golden age of Islam. PMID- 1306871 TI - A preliminary survey for human immunodeficient virus (HIV) infections in tuberculosis and melioidosis patients in Ubon Ratchathani, Thailand. AB - A preliminary survey was conducted for the prevalence of HIV infections in pulmonary tuberculosis and melioidosis patients in Ubon Ratchathani province, in Thailand, the second largest province in population which supplies labors to Bangkok metropolis. In this province, tuberculosis is prevalent in a higher rate than in most other provinces and melioidosis is endemic. Four HIV-seropositives were found in a total of 551 suspected and culture-positive cases of pulmonary tuberculosis, while no HIV-seropositive was found in 121 melioidosis patients. In view of the rapidly expanding HIV-infections in Thailand, a strict watch will be needed on the future epidemiological status of HIV-infection in tuberculous patient. PMID- 1306873 TI - Scientific and humanistic compatibility ... the environment of choice. PMID- 1306872 TI - Outbreaks of paralytic poliomyelitis and polio surveillance in Shandong province of China. AB - Widespread outbreaks of paralytic poliomyelitis occurred in Shandong province, China, starting from 1988. In 1989, 484 cases were recorded, which was the peak during the past 4 years. Although emergency immunization with trivalent oral poliovirus vaccine (OPV) was carried out in selected counties in 1989 and 1990, control of the outbreak was not satisfactory. OPV mass immunization campaigns were introduced to cover the whole province in early 1991, and the number of patients with paralytic poliomyelitis decreased to 95. In addition to this new immunization strategy, we began to construct new polio surveillance systems. These were a network for case-negative reporting and an immediate reporting system of acute flaccid paralysis (AFP). As for the case-negative reporting, presently more than 90% of counties have been reporting presence or absence of new AFP cases. Monitoring of AFP immediate reporting has also shown a gradual improvement in several aspects. These polio surveillance activities are crucial to polio eradication programme management. PMID- 1306874 TI - Your computer and you. Understanding hard disk drives. PMID- 1306875 TI - Missouri law requires report of suspected abuse. PMID- 1306876 TI - Child abuse on the rise. PMID- 1306877 TI - Coalition educates dentists. PMID- 1306878 TI - How to recognize situations that suggest abuse/neglect. PMID- 1306879 TI - Service--the success secret of the 90s. PMID- 1306880 TI - Molecular regulation of hematopoietic cytokines: implications and indications for clinical use in pediatric oncology. AB - Proliferation and differentiation of hematopoietic progenitor cells are regulated by a network of stimulatory and inhibitory cytokines. An understanding of the molecular mechanisms of growth control may provide a physiologic basis for the innovative therapy of bone marrow disorders. Among various accessory cells, bone marrow T lymphocytes are capable of stimulating, as well as inhibiting, hematopoietic progenitor cells. We have now elucidated molecular mechanisms regulating the differential expression of T cell genes encoding for the stimulatory and inhibitory hematopoietic programs. Stimulation of hematopoiesis requires granulocyte-macrophage colony stimulating factor (GM-CSF), whereas inhibition requires interferon-gamma (IF gamma). Both cytokines can be induced by interleukin-2 (IL2). The T cell IL2 receptor consists of a 75 kD chain (p75) mainly expressed on a subset of resting T cells and a 55 kD chain (p55) which is strongly expressed upon T cell activation. P55 and p75 associate on activated T cells to form a dimeric receptor molecule exhibiting high affinity for IL2. The p75 monomer has an intermediate affinity for IL2. Expression of p55 in the context of the high affinity IL2 receptor constitutes a requirement for T cell IFg release. In contrast, p75 alone is capable of mediating the production of GM CSF. Thus, T cells may be capable of selective production of cytokines with specific effects in hematopoietic growth control. Utilizing a human peripheral blood leukocyte genomic library, we identified various clones containing the entire GM-CSF gene, including coding and regulatory regions. Cloning of the GM CSF gene allowed clinical studies utilizing recombinant DNA-derived GM-CSF. Chemotherapy-induced neutropenia contributes to both complications of cytotoxic therapy as well as increased relapse incidence of underlying disease. In a prospective randomized study, we have demonstrated that GM-CSF abrogates neutropenia following aplasiogenic chemotherapy in children and adolescents with solid tumors, and that GM-CSF may reduce the duration of infectious episodes after cytotoxic therapy. Next, we escalated the cumulative doses of cytotoxic therapy in an ablative regimen followed by hematopoietic stem cell transplantation to treat patients with poor prognosis pediatric tumors. Morbidity of this highly toxic ablative regimen depends on the duration of myeloid aplasia. Median duration of aplasia following hyper-VAMP was 13 days with CM-CSF and 29 days without GM-CSF. In addition, we have employed p55 blocking monoclonal antibody for prevention of graft vs. host disease in bone marrow transplantation. The understanding of specific molecular mechanisms of hematopoietic immuno regulation can thus be utilized to provide novel approaches to the treatment of bone marrow failure and cancer. PMID- 1306881 TI - Treatment of de novo acute myelogenous leukemia with recombinant granulocyte macrophage-colony-stimulating factor in combination with standard induction chemotherapy: effect of granulocyte macrophage-colony-stimulating factor on white blood cell counts. AB - GM-CSF is a major regulator of myelopoiesis. Recombinant human GM-CSF (250 micrograms/m2 per day i.v.) was used prior to chemotherapy ("3 + 7" scheme) to recruit leukemic blasts in vivo (de novo AML patients, n = 20) into the chemotherapy sensitive phases of the cell cycle. The stimulatory effect of GM-CSF on peripheral blood AML blasts was associated with a rapid redistribution of leukemic blood cells and with an increase in "S-phase positive" cells. Standard induction chemotherapy ("3 + 7") following GM-CSF induced complete aplasia in 19/20 patients. In the same patients, rhGM-CSF (given after chemotherapy) was found to shorten the time of complete aplasia compared to historical controls whereas post-chemotherapy- and follow-up data suggest no significant differences for CCR and survival. Together, our studies show that GM-CSF can safely be administered to AML patients in combination with induction chemotherapy to recruit leukemic cells into the cell cycle. PMID- 1306882 TI - Biology and pharmacology of hematopoietic growth factors. AB - Several glycoproteins that control blood formation have recently been characterized. Through their overlapping, synergizing, and antagonistic effects, they regulate hematopoiesis in a highly differentiated network. Large scale production of these colony stimulating factors (CSFs) has been made available by recombinant DNA technology, and a series of clinical studies in a variety of indications has been finished. In general, the subcutaneous application seems to be superior to the intravenous injection and causes less toxicity. Erythropoietin has been shown to be a highly effective treatment for anemia in patients with chronic renal failure. Granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor are capable of ameloriating the chemotherapy induced neutropenia, and to abbreviate the time span of myeloaplasia after bone marrow transplantation. The potentials of other colony stimulating factors like Interleukin 1 and Interleukin 3, and combination regimens of several CSFs will be discussed. PMID- 1306883 TI - Introduction of erythropoietin in the treatment of acute lymphoblastic leukemia (ALL) in a patient of Jehovah's Witnesses persuasion: a case report. PMID- 1306884 TI - Use of GM-CSF in children after high-dose chemotherapy. AB - The toxicity and efficacy of recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) is established in adults, but limited information is available on its use in children. The profound myelotoxicity induced by cisplatin (40 mg/m2 daily x 5) and etoposide (150 mg/m2 daily x 3) provides a model to test the clinical value of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric cancer patients; myelosuppression occurred (absolute neutrophil count [ANC] < 500/microL) during 99 of 118 (84%) courses given to 44 children with refractory solid tumors. Fifty-nine courses (50%) resulted in hospitalizations for fever. Subsequently, rhuGM-CSF was added to this treatment regimen to: (i) determine the dose-limiting toxicity of this agent in children; and (ii) to determine whether it can decrease the duration and severity of neurtropenia and attendant complications. Here we summarize and update our experience with this glycoprotein in children with relapsed solid tumors. PMID- 1306885 TI - RhGM-CSF in bone marrow transplantation: experience in pediatric patients. AB - RhGM-CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages. It also stimulates proliferation of endothelial cells and induces the production of other cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non-hematopoietic cell activities. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM-CSF in pediatric patients (age < or = 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venooclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity. PMID- 1306886 TI - Interleukin-3 and granulocyte-macrophage colony-stimulating factor in combination: clinical implication. AB - The multilineage hematopoietic effects of IL-3 appear to be most important for its clinical use comprising especially leucocyte and platelet responses. This was demonstrated to be dose dependent characterising doses of 250 to 500 micrograms/m2/day subcutaneously as hematopoietic effective and well tolerable. Since preclinical data suggest synergism between IL-3 and GM-CSF hematopoietic effects of their sequential administration were evaluated in 15 patients with preserved hematopoietic function. An enhanced stimulation of megakaryopoiesis combined with more pronounced stimulation of granulopoiesis than IL-3 alone could be demonstrated. The cytokine combination of IL-3 and GM-CSF was thus used during chemotherapy induced myelosuppression. Data indicates beyond the known amelioration of myelosuppression by GM-CSF additional chances to enhance platelet recovery which can be of important clinical impact. PMID- 1306887 TI - Value of MRI in head injury. Comparison with CT. PMID- 1306888 TI - [Monitoring of somatosensory evoked potentials during surgery for aneurysms of the sylvian artery]. AB - Per-operative use of S.E.P.s for vascular disease is based on: 1. The relationship between electrical cortical responses and cerebral blood flow. 2. The existence of a reversible threshold of cerebral ischemia. Intra-operative monitoring S.E.P.s were used during 30 procedures for aneurysms of the middle cerebral artery (M.C.A.). In 18 cases, a temporary occlusion of M.C.A. was necessary. Occlusion times ranged from 1 to 30 minutes. The central conduction time delay (C.C.T.), i.e. the delay N14-N20 and the cortical peak (N20) amplitude, elicited by median nerve stimulation was bilaterally monitored. A prolongation of the C.C.T. by 1 millisecond (compared with the baseline induction value) and a progressive decrease or a disappearance of the N20 peak were considered as "significant" changes. In response to these changes, immediate corrective actions (interruption of temporary M.C.A. occlusion (T.O.), repositioning of brain retractors, reapplication of aneurysm clips ...) were implemented. The reversibility of the S.E.P.s alterations during surgery was correlated with the post-operative outcome. Significant changes were found in 20 cases (including 13 T.O.). They were totally reversible in 11 cases: 5 of them developed a new but transient immediate post-operative deficit, none had a definitive deficit, and 6 patients had no new deficit. In 9 cases, the per operative S.E.P.s alterations were not reversible: 3 cases (including 1 T.O.) had a transient deficit, 4 a permanent deficit, and 1 died (aneurysm rupture during craniotomy). An irreversible N20 peak disappearance predicted a permanent post operative deficit in 4 of 4 patients (100%), whereas an isolated irreversible C.C.T. increase was only followed by a transitory deficit. Only 1 of 9 patients with no change in S.E.P.s (during a 15 min. T.O.), had a transient hemiparesis: this "false-negative" case will be discussed. This study confirms that S.E.P.s monitoring provides useful warning during aneurysm surgery. Median nerve S.E.P.s reflect the functional integrity of cortical M.C.A. territory; it is the pathway a risk during M.C.A. aneurysm surgery. S.E.P.s changes are not real-time information (an average of 500 responses need about 2 min), but these delays allow the surgeon to reverse the situation by immediate intra-operative adjustment, especially during temporary M.C.A. occlusion. PMID- 1306889 TI - [Cervical meningocele and meningomyelocystocele. Apropos of 4 cases]. AB - Published cases of cervical dysraphic lesions are rare. Their estimated proportion is about 5% of the entire group of spinal dysraphism. Four cases are reported, representing 2 types of lesion: 2 meningoceles with a simple fibrous band fixing the posterior aspect of the cord to the skin and 2 meningomyelocystoceles with other associated anomalies (hydromyelia, hydrocephalus, Chiari II, Peter's ocular anomaly). The clinical presentation is that of a soft posterior cervical mass without marked neurological impairement. The surgical treatment is simple, consisting in the resection of the lesion, intradural exploration to untighten the cord if fixed by a fibrous band, and drainage of the hydrocephalus. Neurological outcome is generally good immediately but may need sometimes secondary surgical exploration. PMID- 1306890 TI - [Multiple intracranial aneurysms. Endovascular treatment by coils]. AB - The authors report the case of a 30 years-old man presenting with 3 intracranial aneurysms, which were treated by endovascular techniques. The aneurysm responsible for two previous subarachnoid hemorrhages was a giant supracavernous left internal carotid artery aneurysm. Endovascular therapy using coils caused intraoperative rupture which was successfully managed by balloon occlusion of the internal carotid artery. The two other aneurysms (basilar top, and right middle cerebral artery) were small and asymptomatic; complete obliteration of both aneurysms was achieved by selective coils embolization. Persistent occlusion of the three aneurysms was documented ad six months angiographic follow up. PMID- 1306891 TI - [Distal aneurysm of the postero-inferior cerebellar artery. Anatomical and surgical considerations]. AB - A patient with a rare peripheral aneurysm of the posterior inferior cerebellar artery (P.I.C.A.) was treated by microsurgery. Anatomical features and surgical procedures are discussed. The aneurysm was located in the retromedullary, tonsillomedullary segment of the right P.I.C.A. and formed a caudal or infratonsillar loop in the cisterna magna close to the inferior part of the tonsil. The operation was performed with the patient in the sitting position using a median suboccipital approach through a cervical 1 (C1) laminectomy. The widened neck of the aneurysm was clipped successfully and the post-operative course was completely asymptomatic. A vertebral angiogram control showed the P.I.C.A. to be patent. The surgical approach should be related to the site of the aneurysm. Those affecting the telovelotonsillar segment of a P.I.C.A., forming cranial or supratonsillar loops, and those involving its cortical segment can be effectively operated using the same median suboccipital approach. Aneurysms arising from the anterior or lateral medullary segment of a P.I.C.A. should be approached through a unilateral suboccipital craniectomy extending down to the foramen magnum. Although clipping the neck of the aneurysm is preferable, trapping is possible for lesions arising from or distal to the telovelotonsillar segment, this preserving the small arteries arising from the lateral and posterior medullary segments. PMID- 1306892 TI - [Cerebral alveolar echinococcosis. Apropos of a surgically-treated case. Review of the literature]. AB - The authors present a case of a cerebral echinococcosis in a male farmer operated upon 9 and 6 years ago for pulmonary and hepatic localisations of Alveolar Echinococcosis. Cerebral lesions were diagnosed by CT scan and MRI and were totally removed. The follow-up was uneventful. A review of the literature revealed only eighteen previously reported surgical cases. The authors comment the epidemiology of this endemic parasitic disease, and the particular aspects of its cerebral localisation. PMID- 1306894 TI - [A rare case of intramedullary epidermoid cyst diagnosed by MRI]. AB - Intramedullary epidermoid cysts are rare entities. A case recently seen on MRI led us to review the literature on the subject. A 9 year old boy developed in a four month-time a spastic paraparesis with a T7-T8 sensitive level. The MRI showed a widening of the spinal cord at the T6 level with an area of decreased signal on T1 weighted images, and a homogeneous round shaped area of increased signal on T2 weighted images. The authors discuss the contribution of MRI to the diagnosis of this lesion. The number of cases of intramedullar epidermoid cysts, like dermoid cysts, diagnosed with this neuroradiological method, is still very limited and the literature only mentions isolated cases. PMID- 1306893 TI - [Primary Meckel's cave lymphoma. A case and review of the literature]. AB - A rare case of Meckel's cavity lymphoma is presented. Only two other cases of identical localization have been presented in the literature. The symptoms consisted of sensorimotor impairment of the Vth nerve associated with slight exophthalmos. C.T. scan showed a hyperdense lesion in Meckel's cavity. After total surgical removal, histological analysis diagnosed a B-lymphocyte non Hodgkin's lymphoma. The patient received both radiotherapy and chemotherapy and at one year follow up, the clinical course was good. The lesion had no clinical or radiological specificity. Its prognosis appears to be identical to that of other intracranial lymphomas. PMID- 1306895 TI - [Contribution of ultrasonic cavitation--CO2 laser combination in the excision of panmedullary ependymoma]. AB - The authors report an uncommon case of panmedullary ependymoma (C2 to T12), totally removed in one stage with the use of ultrasonic cavitation and CO2 laser. The preoperative topographical diagnosis without M.R.I. was very difficult. CO2 laser in addition with ultrasonic cavitation allows the removal of the tumor without any prohibitive tractions on the spinal cord. The stable course with a long follow-up period (seven years) confirms the good prognosis of such a pathology. PMID- 1306897 TI - Case #11. Recurrent intraoral herpes. PMID- 1306896 TI - [Religious delusion 13 years after brain injury]. AB - We report here with a case of religious delusion in a 39 years old woman. She had suffered a head injury with right temporal concussion 13 years before but had no earlier history of psychiatric disorder. In view of the fact that this acute psychiatric state lasted for a short duration of time and that personality and affects were preserved, this incident is compared to the schizophreniform disorder of the type DSM-III-R. The hypothesis of an acquired predisposition due to head injury has been put forward as an explanation. PMID- 1306898 TI - Consider each patient's need when assessing perio disease. PMID- 1306899 TI - Wide variety of barriers protect providers, patients, environment. PMID- 1306901 TI - Quest for knowledge. PMID- 1306900 TI - Food for lifelong living. PMID- 1306902 TI - When tragedy strikes. PMID- 1306903 TI - It's not just what you say, but how you say it to your patients. PMID- 1306904 TI - Let's take the steps to keep our basic education intact. PMID- 1306905 TI - Case #12. Fusion. PMID- 1306906 TI - Restorative work possible reason for localized tissue inflammation. PMID- 1306908 TI - Identifying regulated waste source of confusion for some. PMID- 1306909 TI - It's time to solve the 'dental hygiene problem'. PMID- 1306910 TI - Update and literature review of bruxism. PMID- 1306911 TI - Bruxism and bruxomania. PMID- 1306912 TI - Broiler chicken production in the hot season in Sudan. PMID- 1306913 TI - An outbreak of theileriosis in sheep in Sudan. PMID- 1306914 TI - Trypanosomiasis control in Boran cattle in Kenya: a comparison between chemoprophylaxis and a parasite detection and intravenous treatment method using isometamidium chloride. AB - Two methods of trypanosome control in Boran cattle kept under very high trypanosomiasis risk were compared: the traditional intramuscular isometamidium chloride prophylaxis with a parasite detection and intravenous isometamidium chloride treatment method. The results were related to a control group under diminazene aceturate treatment. Isometamidium chloride at 0.25 mg/kg as routinely used by the ranch was of little benefit by either method, with breakthrough infections occurring as early as one week after treatment. When isometamidium chloride at 1 mg/kg was used, the curative intravenous method appeared to be superior to the intramuscular prophylaxis with regard to cost of drugs and to a 31% higher weight gain over a 30 week period. Weekly infection rates in the intravenous group decreased over time, despite an increasing trypanosomiasis challenge, with a mean interval of 6.4 weeks between treatments as compared with 4.3 weeks in a diminazene aceturate control group. It was concluded that isometamidium chloride given intravenously had not only a very good therapeutic but also a considerable prophylactic effect of not less than four weeks. PMID- 1306915 TI - Anaplasmosis in Uganda. I. Use of dried blood on filter papers and serum samples for serodiagnosis of anaplasmosis--a comparative study. AB - The suitability of blood collected on filter papers in comparison with corresponding conventional serum samples in the diagnosis of bovine anaplasmosis was studied using the complement fixation test, DOT-ELISA, Western immunoblot and rapid card agglutination test. Dried blood on Whatman filter paper no. 1 was eluted in PBS 0.05% Tween 20 giving an initial dilution of 1:10. The reactivity of the eluted samples in both DOT-ELISA and Western immunoblotting were similar to those obtained with the corresponding straight serum sample dilutions. Filter paper samples gave lower reactivity in the remaining tests when compared with corresponding serum samples. There was no significant difference in the reactivity between the eluates from filter papers stored at temperatures ranging between 15.5 and 24 degrees C and those kept refrigerated. Storage at 15.5 to 24 degrees C did not significantly affect reactivity for up to six months. Eluates from filter papers stored for six months at 15.5 to 24 degrees C continued to give similar reactivity as those from freshly prepared filter papers in both DOT ELISA and Western blot, and in the rapid card agglutination test. It is concluded that collecting blood on filter papers is a suitable technique for large scale seroepidemiological studies on anaplasmosis and offers many advantages in developing countries where transport and cold chain facilities are a major constraint. PMID- 1306916 TI - Epidemiology of sheep myiases in Sao Paulo State, Brazil. AB - A survey of Diptera species causing cutaneous myiases on sheep in Botucatu, Sao Paulo, Brazil was made to determine seasonal incidence, predilection sites and the factors predisposing to infestation. Sheep were checked daily for myiases for one year. At two week intervals larvae from wounds were collected for identification. Only larvae of Dermatobia hominis and Cochliomyia hominivorax were found. Myiases due to C. hominivorax were observed during the whole year with high incidence from January to April. The feet, vulva, tail and scrotum were most frequently infested. Wounds were the commonest predisposing factor. PMID- 1306917 TI - An evaluation of serologic tests used to diagnose brucellosis in buffaloes (Bubalus bubalis). AB - Five serologic procedures were evaluated in buffaloes and results compared with cultures of 64 udder secretion specimens. The rivanol test was superior to all other methods in specificity. The card, rivanol and complement fixation tests identified all infected cows. Many sera had complement fixing antibodies while agglutinins were absent. It was concluded that these were false positive results. A new procedure, the particle concentration fluorescence immunoassay, was a sensitive screening test but lacked specificity. On a limited number of samples, the tube agglutination test lacked sensitivity and was not a very useful procedure for the diagnosis of brucellosis. All 18 isolates of Brucella abortus were biovar 1. PMID- 1306918 TI - Control of brucellosis in Kuwait by vaccination of cattle, sheep and goats with Brucella abortus strain 19 or Brucella melitensis strain Rev. 1. AB - In Kuwait, approximately 12,000 dairy cows were vaccinated with a reduced dose of 3 x 10(9) Brucella abortus strain 19 and approximately 350,000 sexually mature sheep and goats with a reduced dose of 10(7) B. melitensis strain Rev. 1. Using the criteria of prevaccinal and postvaccinal incidences of antibodies, abortions, and human cases of brucellosis, the programme was very successful. Widespread vaccination of adult animals is the most effective method of controlling brucellosis among cattle, sheep and goats in many countries. PMID- 1306919 TI - Seasonality of cattle feed sources in Pabna, Bangladesh. AB - Cattle feed sources were studied at village level in Pabna district, Bangladesh. A large quantity of feed was offered. In the monsoon the average amount of DM fed to a mature animal of 210 kg was 7.1 kg d-1, consisting of about equal amounts of straw, weeds and leaves. In winter animals grazed for an average of 3.7 hd-1 and were supplemented with 3.9 kg DM d-1 (two-thirds straw). In summer they were offered 5.4 kg DM d-1 (one-third straw and two-thirds weeds and leaves) and they grazed for 0.5 h d-1. The major limiting constraint on cattle production is the quality of the feed offered, particularly in the monsoon period when animals cannot graze. In future, feed quality will become even more of a problem because grazing lands are gradually disappearing. PMID- 1306920 TI - Effects of parasitic infestation on the productivity of alpacas (Lama pacos). AB - A trial was carried out in alpacas (Lama pacos) to determine the economic benefit of controlling both external and internal parasites using ivermectin (Ivomec, Merck, Sharpe and Dohme). After four months the treated male alpacas had gained on average 3.1 kg more than the untreated males and their fleece weighed 0.36 kg more. Treated females gained 1.9 kg more than the controls but their fleece weighed 0.03 kg less. This resulted in a net financial benefit to the farmer of US$3.54 for each male alpaca and US$1.36 for each female. PMID- 1306921 TI - Prevalence of Babesia bovis and Anaplasma marginale at selected localities in Sri Lanka. AB - Sera were collected from a minimum of 20 cattle aged nine to 36 months at each of 14 localities in five climatic zones of Sri Lanka. Sera were tested for antibodies to Babesia bovis and Anaplasma by an indirect fluorescent antibody test and a card agglutination test, respectively. Antibodies to B. bovis and Anaplasma were detected in all samples tested from each of 14 and 12 localities respectively. In general, prevalences were consistently high among localities below 1,200 m and lower and more variable in the hill country. Management practice rather than climate was considered to be the main factor influencing prevalences. Management is discussed in relation to the risk of disease outbreak. PMID- 1306922 TI - A lawyer's thoughts on dental jurisprudence. PMID- 1306923 TI - [Midline granuloma and Wegener's granulomatosis]. AB - Necrotizing lesions of upper respiratory tract have always been among the most enigmatic diseases of the head and neck region. Nowadays a great deal of nosographic confusion still remains along with numerous doubts concerning diagnostic and therapeutic strategies to be followed in dealing with many diseases often erroneously defined "midline granuloma". In fact, a large variety of diseases appear or may appear as midline destructive lesions in the upper respiratory tract. Each of these, including infections, immune and neoplastic disorders, obviously requires a different therapy. The clinician must have a very good knowledge of the problem in order to make a rational approach to diagnosis and therapy. Wegener's granulomatosis is quite different from "midline granuloma" and must be diagnosed promptly so that an appropriate therapy may be determined as soon as possible. Unlike in the case of "midline granuloma", a prompt therapy is often very effective and gives long periods of remission. In this disease, nevertheless, the etiopathogenesis of both diseases is unknown, precise protocols for diagnosis or treatment do not exist (every case must be considered separately) and prognosis is very poor. On the basis of their personal experience and of an accurate review of Literature, the Authors present a systemic and up-to date monographic study focusing particular attention on the most recent diagnostic techniques, such as immunohistochemical techniques which utilize monoclonal antibodies, indispensable in the cases of "midline granuloma", and immunofluorescent techniques searching antibodies to cytoplasmic antigens of neutrophil granulocytes, of great value in dealing with Wegener's granulomatosis not only in establishing an initial diagnosis, but also in making prognosis and in controlling the evolution of the disease. The paper also discusses differential diagnosis of midline destructive disorders, highly important for a correct and rational initial approach in diagnosis. Every disease described in the section concerning differential diagnosis must be excluded in order to make an accurate diagnosis of "midline granuloma" in that no typical histopathologic or clinical signs of this particular, destructive disorder. Finally, the authors focus their attention on new etiopathogenetic hypotheses and their therapeutic implications. The most interesting of them are surely those that consider "midline granuloma" the manifestation of a malignant lymphoma as well as those that explain the recent success obtained in treatment of Wegener's granulomatosis using trimethoprim and sulfamethoxazole asserting a possible essential role of infections in the etiology of the disease. PMID- 1306924 TI - Treatment of testicular relapse in childhood acute lymphoblastic leukemia. AB - The experience of rescue therapy for 6 patients of childhood acute lymphoblastic leukemia (ALL) with testicular relapse is reported. In two patients, testicular relapse occurred 1 and 4 years off therapy, respectively. Two patients had testicular relapse on therapy. The remaining 2 patients had testicular relapse after premature discontinuation of therapy by the parents. Isolated testicular relapse was found in 2 patients. The rest of the testicular relapses were concurrent with either bone marrow (BM) or central nervous system (CNS) relapses. The rescue therapy included bilateral testicular irradiation 24 Gy, and systemic reinduction chemotherapy, followed by maintenance therapy as that of TCL 821 or TCL 842 protocol for high risk patients of ALL. CNS prophylaxis, which included intrathecal medication and/or cranial irradiation 18 Gy (if not given before), was also given. After testicular relapse, one had subsequent BM and CNS relapses and received more aggressive chemotherapy. Another one had subsequent CNS relapse 4 months after another premature withdrawal of treatment. One patient, who presented with CNS leukemia at diagnosis, had concurrent testicular and CNS relapses and died of CNS leukemia 3 months later. The remaining 5 patients remained in continuous complete remission for 26 to 95 months with a median duration of 54 months. PMID- 1306925 TI - Clinical use of single-dose surfactant TA therapy for premature infants with severe respiratory distress syndrome. AB - A single dose of surfactant TA was given as rescue therapy to four small premature infants with severe respiratory distress syndrome requiring mechanical ventilation. Birth weights ranged from 810 to 1200 gm. The dose of 100-120 mg/kg was given at the mean age of 5 hours, with range of 3 to 7 hours. Following surfactant therapy, there was a significant improvement (p < 0.05) in a/APO2 (raising from 0.11 +/- 0.05 before treatment to 0.34 +/- 0.19 at 6 hours after treatment). There was also a significant reduction in the severity of respiratory distress syndrome at 24 hours post-therapy. One baby died of sepsis at 40 hours of life; one survived without complications. The other two cases developed severe bronchopulmonary dysplasia later. We concluded that early use of exogenous surfactant is beneficial in small premature infants with severe respiratory distress syndrome. PMID- 1306926 TI - Auditory brainstem responses in term neonates treated with gentamicin. AB - Seventeen infants who had been treated with gentamicin on the first day of life as prophylaxis for prolonged rupture of membranes or maternal fever. Twenty-seven weight-matched healthy infants were used as controls. The auditory brainstem responses were evaluated on the third day and again on the tenth day of life. Latencies of components V, intervals I-V and III-V were significantly prolonged in the gentamicin treated group when compared with the control group. This prolonged latencies reversed itself on the tenth day of life. The concentration of peak and trough levels of gentamicin were related to latency of interval III V. These findings emphasize that a short course therapy with gentamicin in essentially healthy infants can alter the central transmission of auditory brainstem responses transiently. PMID- 1306927 TI - Atlantoaxial subluxation and syringomyelia in Down syndrome: report of one case. AB - Atlantoaxial instability is a relatively frequent finding in Down syndrome, but syringomyelia is a rare symptom. A four-year-old girl with Down syndrome was noted to have one year history of torticollis and progressive motor deterioration presenting with abnormal gait, ataxia or quadriparesis for the past three months. She was admitted because of acute urinary retention. Physical examination showed distended urinary bladder, hyperreflexia, bilateral ankle clonus and the existence of Babinski's signs. The x-ray films of the cervical spine showed widening between the joint space of atlas and odontoid processes. Magnetic resonance imaging revealed C1-C2 subluxation with syringomyelia. After bladder training and cervical orthosis, the symptoms improved. PMID- 1306928 TI - Rotor's syndrome: report of one case. AB - Rotor's syndrome is a rare hereditary non-hemolytic hyperbilirubinemia. This report concerns an 11-year-old boy who presented with fluctuant jaundice since birth. Liver function tests showed conjugated hyperbilirubinemia with normal serum aminotransferase and globulin level. The diagnosis was confirmed by laboratory workup which included normal liver histology and oral cholecystography and typical sulfobromophthalein excretion curve. PMID- 1306929 TI - Pseudo-trisomy 13 syndrome: report of one case. AB - A new syndrome associated with holoprosencephaly, midline facial defects and postaxial polydactyly but normal chromosomes was described. The term "pseudo trisomy 13 syndrome" was used because of the resemblance to trisomy 13. Only a few cases have appeared in the literature, and this is the first chinese case. PMID- 1306930 TI - Intestinal malrotation and gastric perforation in a newborn with tetralogy of Fallot: report of one case. AB - Gastric perforation with gastrointestinal anomaly is rare in newborns. A case of Tetralogy of Fallot with both malrotation and gastric perforation is reported. Before operation, malrotation was diagnosed from the x-ray films. Laparotomy disclosed a linear perforation on the posterior wall of the gastric body. Mechanical obstruction might have played a role in this case. PMID- 1306931 TI - Renal cell carcinoma in childhood: report of one case. AB - Renal cell carcinoma is extremely rare in children. A case is reported here of renal cell carcinoma in a seven-year-old boy whose clinical manifestations were fever and right loin pain. Imaging studies revealed a solid mass in the right kidney and a metastatic nodule over the middle lobe of the right lung. Right nephrectomy and middle lobectomy of the right lung were performed. Pathologic examination revealed a renal cell carcinoma with predominance of clear cells. Despite Stage IV, the patient is still alive without chemotherapy and radiotherapy. It should be emphasized that renal cell carcinoma should be included in the differential diagnosis of pediatric renal solid masses, particularly in older children and adolescents. PMID- 1306932 TI - Graves' disease associated with myasthenia gravis: report of one case. AB - Exophthalmos occurs in more than half of the patients with childhood Graves' disease, while severe Graves' ophthalmopathy is uncommon in children. Myasthenia gravis is even more rare in association with Graves' disease. A 7-year-old girl is reported; she had ptosis for two years; this was treated irregularly, and she then developed exophthalmos, ophthalmoplegia and thyroid goiter. Her laboratory tests showed T3 496 ng/dl, T4 17.05 ug/dl, TSH < 0.1 uU/ml, fT4 > 4.2 ng/dl. Antithyroglobulin antibody was 1:25600 and antimicrosomal antibody was 1:102400. Myasthenia gravis was confirmed by a positive neostigmine test. Due to allergic reaction to propylthiouracil, she was treated with carbimazole and propranolol. Thereafter the thyrotoxicosis was was well controlled. The ocular-type myasthenia gravis remained stable with minimum medical treatment. PMID- 1306933 TI - [Acute scrotal gangrene: report of one case]. AB - Acute scrotal gangrene is a rare urologic emergency that is especially uncommon in children. It is characterized by an abrupt onset in an otherwise healthy individual, rapid progression to gangrene, and ill-defined etiology. A twenty three-day-old male infant with complaints of irritable crying, fever, and scrotal swelling was admitted to this hospital. Physical examination showed scrotal edematous swelling and skin discoloration. Ultrasound examination, culture of scrotal content and scrotal biopsy confirmed this diagnosis. After surgical drainage and treatment with strong antibiotics, the patient was recovered uneventfully. Acute scrotal gangrene is very rare, especially in early infancy, therefore, it is important to recognize the disease and be careful to make differential diagnosis with other disease, especially testicular torsion, and strangulated hernia to avoid unwarranted, complication or surgery. PMID- 1306934 TI - [Preoperative evaluation of respiratory function]. PMID- 1306935 TI - [Preoperative evaluation of respiratory function in thoracic surgery. Do reliable predictive criteria exist in that type of surgery?]. AB - A cautions analysis of the respiratory preoperative study may decrease morbidity and mortality after pulmonary surgery. To search for predictive criteria of respiratory complications following this kind of surgery, 454 patients have been studied retrospectively. Morbidity was defined as the need for postoperative ventilation. Preoperative criteria were divided in clinical (age, obesity, history of pulmonary disease, dyspnea, score of Karnofsky), laboratory (blood gases, spirometry) and surgical (kind of procedure). Three criteria were significant for morbidity (15 ventilated patients) and mortality (27 deaths): age (> 65 years), obesity, hypocapnia (pCO2 < 4.1 kPa-31 mmHg). Analysed spirometric values were no significant. PMID- 1306936 TI - [Value of sophisticated explorative techniques of the pulmonary function in the preoperative evaluation of respiratory risk]. AB - In order to estimate the preoperative evaluation of the respiratory risk, a well adapted clinical examination associated with a routine pulmonary function test (VC, FEV1) can be sufficient. Although some patients with cardiopulmonary disorders or candidates to lung resection need more complex assessments: the flow volume loop to detect small airways obstruction (MEF 50%, MEF 25%), measure of bronchial hyperreactivity to predict bronchospasm during anaesthesia, residual volume for the diagnosis of emphysema, diffusing capacity (DCO) to discover lung fibrosis: these parameters disruption always make the pronostic worse. It is also useful to couple together preoperative function test and pulmonary scintigraphy to predict post-operative values after lung resection. But, these criteria for operability are not always a good indicator of post-operative complications. So it is possible to use in addition the results of exercise testing to determine cardio-respiratory performances and maximal oxygen consumption (VO2MAX) which seem better correlated with mortality and post-operative lung surgical complications. Preliminary results of our study concerning thirty patients hospitalized in Besancon-St-Jacques Hospital, agree with the hypothesis that exercise testing is an important criterion in the pre-operative evaluation and to predict post-operative mortality and morbidity of patients candidates to thoracic surgery. PMID- 1306937 TI - [Choice of respirators for anesthesia]. AB - Criteria of quality of gases and vapours supply, ventilator, patient's circle circuit and monitoring devices are recalled to help the anesthetist to choose his anesthesia machine. Advantages of compact or modular apparatus are discussed. Four, now wellknown, anesthesia machines (modulus II+, Siemens 900 D+SAC985, Roche Kontron 4300 and Engstrom Elsa) were analysed in clinical controlled ventilation and in simulated spontaneous ventilation to study the imposed work of breathing. Results are discussed with regard to safety rules and to ergonomics, bearing in mind their respective prices. Comparison is made with an original "bisontin" prototype. PMID- 1306938 TI - [Transtracheal jet ventilation in the operating room]. AB - For the last 40 years transtracheal ventilation has been suggested as a means of bypassing the glottis in emergency in patients unable to be intubated or ventilated by mask. A catheter has been designed to be easily inserted into the crico-thyroid membrane. The outer part of the device, with its dual attachment system, can be connected to conventional resuscitation equipment by its 15 mm male end or to a high-pressure oxygen source by its Luer-Lock fitting. The advantages of transtracheal ventilation are: a clear vision of the operative field, a good gas exchange, an elimination of airway trauma from intubation, a reduction of the hazard of airway fires and a decreased risk of aspiration of blood and debris. Barotrauma is the main danger. However, this method of providing oxygen and/or mechanical ventilation may be extended to the postoperative period, the exit of the insufflated gas mixture being assured at all times. PMID- 1306939 TI - [Early postoperative hypoxia]. AB - Disturbances of the oxygenation of a patient during the early postoperative period occur frequently. Their mechanisms are complex. Alveolar related hypoxemia can be distinguished from pulmonary or nonrespiratory related hypoxemias. Those of alveolar origin are characterized by a drop in the alveolar oxygen pressure. Those of pulmonary origin arise mainly due to ventilation perfusion distribution problems or an increase in the intrapulmonary shunt. Those of nonrespiratory origin are mainly caused by a drop in cardiac output or by an increase in the tissular oxygen consumption. Patients showing signs of postoperative oxygenation trouble usually recover rapidly. Severe cases require intensive care treatment. PMID- 1306940 TI - [Management of failure of loco-regional anesthesia]. AB - Sedation for patients during surgery under local or regional anaesthesia may induce ventilatory depression. All sedated patients must be monitored with a pulse oximeter. Routine administration of supplementary oxygen is necessary. General anaesthesia must be rapidly performed when regional anaesthesia is unsuccessful. PMID- 1306941 TI - [Automatic measurement of blood pressure: limits of oscillometric technique]. AB - Non invasive blood pressure (NBP) measures are currently used in anesthesiology. The accuracy of this oscillometric technic has been tested with healthy patients, but not often with a wide pattern of pathology. The aim of this study is to point out the reliability of NBP during vascular surgery with patients suffering from arterial disease and atherosclerosis. It compares outcome with simultaneous catheter arterial blood pressure measurement (template technic). In this conditions, oscillometric method underestimates the systolic pressure value, and overestimates the diastolic one. The higher the level of arterial pressure is, the larger is the difference between this methods. It is clear that the automatic oscillometric technic is not so reliable if hypertension or atherosclerosis disease occurs. In order to improve this technic, automatic measures must take in account the degrees of arterial rigidity in its outcome. PMID- 1306942 TI - [From central venous pressure to SVO2]. AB - The interest and the limits of different hemodynamic parameters are recalled: measure of right arterial pressure and pulmonary artery pressure, continuous measurement of SvO2. Technological and theoretical knowledge are necessary to interpret the results. PMID- 1306943 TI - [Surgery of the aortic bifurcation and heart diseases: peroperative hemodynamics]. AB - During aorto-biiliac by-pass, patients with heart disease are exposed at many haemodynamic problems. Mixed venous oxygen saturation monitoring help anesthetist along clamping and unclamping periods. This study concerning 13 patients with pre operative NYHA class II and III congestive heart disease, discusses therapeutic algorithm especially for choosing inotropic or vasodilatator drugs. PMID- 1306944 TI - [Respiratory and cardiac manifestations of anesthesia]. PMID- 1306945 TI - [Hemodynamic complications during the recovery period after anesthesia]. AB - In the postoperative period the alterations of blood pressure are the main hemodynamic complications. Hypotension or hypertension may compromise the coronary circulation and increase the metabolic demand of the myocardium. Pulmonary oedema is the most frequent manifestation of heart failure. The aim of its treatment is to increase myocardial contractility and decrease the metabolic demand. Myocardial ischemia is mostly silent and is an important correlate of adverse cardiac outcomes. The treatment of these hemodynamic events starts during the peroperative period by prevention of their risk factors. PMID- 1306947 TI - [Controlled hypotension? Watch the capnograph closely!]. AB - During the surgery of the middle ear, a profound general anaesthesia associated to the monitoring of arterial hypotension may obtain a fiel of operation free of any blood. The patient surveillance needs the modern techniques of monitoring. SaO2 is altered only for severe falls of mean arterial pressure. PetCO2 reflects three factors: the cellular metabolism that is stable under general anaesthesia, the ventilatory conditions which are controlled and haemodynamic conditions. The cellular metabolism and the ventilatory being stable, PetCO2 modifications reflect mean arterial pressure variations. We have observed minimal falls of PetCO2 (2-3 mmHg) accompanying falls of mean arterial pressure. Monitoring mean arterial pressure every 5 minutes neglects periods of time. On the contrary capnography allows a constant haemodynamic survey. The capnography seems to be a precious help during the technique of controlled arterial hypotension. PMID- 1306946 TI - [Postoperative analgesia by intrathecal morphine and respiratory depression: value of low doses (apropos of 285 cases)]. AB - Morphine at very low dose gives a good post-operatory analgesia without major secondary effects. This study analyses retrospectively 285 spinal anaesthesia with hyperbaric 0.5% bupivacaine 0.2 mg.kg-1 and morphine 0.25 mg in adult urologic surgery. The analysis of enquiry in analgesic during the post-operatory period shows that in most cases (72%) the patients have supported the first 24 hours without any complementary analgesia; 28% of patients needs a complementary analgesia realized with 1 g of paracetamol. Intravenous morphinics have never been necessary in post-operative period. The analgesia was adequate for the patient's comfort, and it never mask a surgery complication. No respiratory complication appeared, even in 13 patients who needed intravenous morphinics in per-operative. PMID- 1306948 TI - [What kind of monitoring for what patient?]. AB - This study assesses theoreticals indications of cardiovascular monitoring in adult non cardiac surgery. These purposes are depending on patient's preoperative evaluation, operative and anesthetic risk, like current technical possibilities. PMID- 1306949 TI - High-level aminoglycoside resistance in enterococci. AB - In recent years enterococci have been isolated with increasing frequency in association with serious infections. Suitable therapy for empirical treatment can only be chosen on the basis of susceptibility studies. The synergistic effects obtained by the combination of aminoglycosides with penicillin or vancomycin disappear in strains that show high level resistance (HLR) to the former. This highlights the importance of correct identification of the species of Enterococcus (especially Enterococcus faecium, a particularly resistant species), and of studies designed to examine HLR in severe infections. The preferred methods are dilution in solid or liquid medium with 2,000 micrograms of aminoglycoside per ml, or diffusion in solid medium from discs impregnated with 120 micrograms of gentamicin (which also predicts the microorganism's susceptibility to tobramycin and netilmicin) or kanamycin (which also predicts the response to amikacin), and 300 micrograms of streptomycin, for Enterococcus faecalis. The reliability of automated systems for the prediction of HLR to aminoglycosides has yet to be assessed. PMID- 1306950 TI - Determination of plasma delta-aminolaevulinic acid levels. Applications. AB - Determination of plasma delta-aminolaevulinic acid levels is of interest for the diagnosis of disorders of heme biosynthesis. We describe a reliable method for the determination of this parameter, based on a modification of the original method of Mauzerall and Granick. Analytical criteria are defined and the reference range used, established using data from 40 subjects, was 0.30 to 1.20 mumol/l. Results in patients with porphyria or lead poisoning and in those treated with haemodialysis or anticonvulsants indicate that this determination could be used principally in the diagnosis and management of acute porphyrias and in the early laboratory diagnosis of lead poisoning. PMID- 1306951 TI - Gel-test: interpretation and value of a new technique for the detection of irregular antibodies. AB - Here we report on our experience with the use of a 'Gel-Test' (DiaMed-ID Micro Typing System) technique for the detection and identification of irregular antibodies in a general hospital. This easy-to-use, standardized technique poses the question of the impact of its sensitivity on the specificity of the results. Of the 10% of observed positive reactions, 3.7% were irregular antibodies, 3.8% papain auto-antibodies, 1% cold antibodies and 2% not elucidated. Two hundred and eighteen irregular antibodies identified and titred with the 'gel-test' system were tested in parallel by 'tube' method. Sixty-three of these antibodies (29%) were not detected by the 'tube' method. While anti-Kell was always detected by both methods, we found the following false natives with the tube method: 15% anti D, 32% anti-E, 42% anti-Cw and 58% anti-Lea. 68% of these false negatives had a low titre. The immunoglobulin class of the anti-E was studied; the sensitivity of the 'gel-test' system was associated with IgM in the anti-E. The sensitivity and standardization of the 'gel-test' technique guarantee greater safety in blood transfusion and increase efficiency in the prevention of foeto-maternal stimulation of anti-D. PMID- 1306952 TI - [The role of ultrasound technique in blood group typing]. AB - The work presented here concerns the study and fabrication of a robot. This tool allows one to bring out the enormous potential represented by the interaction of ultrasounds with globular suspension. The traditional hemagglutination techniques employ the systematic use of a centrifuge and mechanical suspension. The advantage of these processes is the acceleration of reactions, however, the major inconvenience remains in the difficulty of automating these tests completely, especially when microplaques are used. Our study demonstrates that the force of the ultrasonic radiation created in an atmosphere of suspension is susceptible to replacing all mechanical movements. In a stationary ultrasonic field the erythrocytes in suspension assemble towards the pressure points. This phenomenon is characterized by a faster rate of sedimentation favoring agglutination as well. Under certain conditions the ultrasonic bundle produces small whirlwinds in the bowl. The result of this process is the homogenization of the suspension which permits the differentiation between the positive and negative reactions. With these observations in mind we developed a programmable robot prototype, the goal of which was to provide us with a means of greater investigation. The originality of this technique necessitated the realization of a high frequency ultrasound captor with large range and power. For supplying the necessary energy to the transducer we developed an electronic force based on the principle of commutation. The automation is controlled by a programmable microsequensor. This instrument will allow a standardization of a protocol primarily for tests of the group ABO. The results obtained are very encouraging; the next step is to further advance experimentation in more delicate tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306953 TI - Immuno-metabolic factors in schistosomal hepatic fibrosis modulating atherogenesis. AB - Clinical expression of atherosclerosis is infrequent among patients with schistosomal hepatic fibrosis (SHF), besides, the latter disease is a disease with many immunological expressions. The aim of the present work was to search for a possible immunological and metabolic interaction which would modulate atherogenic mechanisms. The study was carried out on 31 patients with SHF and 20 non-schistosomal subjects (10 with evident clinical atherosclerosis and 10 without). All investigated subjects were males aged above 40 years, and were subjected to the following: serum lipoprotein pattern, total cholesterol, phospholipids, triglycerides, ApoA, ApoB, IgG, IgM, IgA, C3 + circulating immune complexes (CICs) and passive haemagglutination using S mansoni adult worm antigens. The results showed low levels of blood lipids in patients with SHF especially in those with porto-systemic collaterals; serum levels of IgG and IgM were significantly increased in all patients with SHF, while IgA was only increased in patients with collaterals who in turn showed the least incidence of clinically evident atherosclerosis; serum C3 was increased in patients with clinical atherosclerosis, both schistosomal and non-schistosomal. CICs have been higher in patients with SHF without atherosclerosis while decreased in atherosclerosis patients, both schistosomal and non-schistosomal. Our results may consolidate the view of a protective role of liver affection against atherogenesis as well as the important contribution of the immune mechanisms in this context. PMID- 1306954 TI - [Polymerase chain reaction: general methodology]. AB - The polymerase chain reaction method (PCR) is extremely sensitive and needs a precise control of the different steps and analytes of the reaction. In this article, we described the principle of the method and the characteristics of the main enzyme, the Taq polymerase. The concentration range of the analytes is reviewed to optimize the amplification of the nucleic acid sequence. PMID- 1306955 TI - Polymerase chain reaction and other methods to detect hot-spot and multiple gene mutations. AB - Gene mutations responsible for main genetic diseases as Duchenne/Becker muscular dystrophy or cystic fibrosis, and involved in more important diseases like cancer or cardiac diseases have been identified. Direct DNA tests can now be performed for these disorders. However, despite the knowledge of the exact alteration of the DNA sequence in these diseases, incorporating DNA analysis into large screening programs has been hindered by technical difficulties since each different mutation requires a different probe to be detected. To overcome these problems the polymerase chain reaction technique (PCR) has been proposed. Multiplex PCR procedure is possible and consists of simultaneously amplifying several separate DNA sequences (the upper limit of the number of multiplex reactions that can be executed at one time is not known; eight or nine separate DNA sequences amplified have already been described). Another approach is to directly sequence the gene mutations generally concentrated in 'hot-spot' regions. This way it is possible to identify numerous mutations using only one micro-sequencing reaction (50-100 nucleotides). New generations of very sophisticated systems like capillary electrophoresis or non-isotopic, but very sensitive, microsequencing systems should allow in a near future to withdraw the use of PCR for this purpose. PMID- 1306956 TI - [Detection of nucleic acid sequences by bioluminescence. Importance of an internal reference system for qualitative and quantitative analysis]. AB - Various luminescent detection systems were used to detect and quantify simultaneously several probes. For quantitative analysis, one probe was used as an internal standard to evaluate the amplification yield and the others to quantify the amplified target. After using hybridization in solution, accurate results were obtained. For a qualitative analysis, amplified sequences were hybridized to specific oligonucleotides which were labelled or immobilized. To compare amplified fragments to products of known sequences, we developed a more efficient technique based on DNA strand exchange occurring during hybridization in solution. This method allowed to detect a single base substitution in DNA fragments of 280 base pairs. PMID- 1306957 TI - Standards and controls in DNA assays. AB - Automated methods are described that begin to standardize genetic analysis at the DNA level. These new methods complement existing automation such as DNA extraction, liquid-handling robotics, thermal cycling and computer information management systems. Using electrophoresis, several independent genetic loci can be analyzed simultaneously using multi-color fluorescent gel scanning detection where DNA segments labeled with up to four different fluorescent dyes are analyzed within a single electrophoresis lane. The amounts and molecular lengths of PCR products are determined with high accuracy and precision by co electrophoresis with a uniquely colored internal standard. These new methods have the potential of minimizing variations in results among different laboratories. PMID- 1306958 TI - [Evaluation of deproteinization and hydrolysis stages during free and total carnitine assay]. PMID- 1306959 TI - [IgG subclasses and T-B cooperation]. PMID- 1306960 TI - [Recommendations for a comparison of techniques. Document F, stage 3]. PMID- 1306961 TI - Quantities and units for metabolic processes as a function of time: recommendations 1992. PMID- 1306962 TI - Flow cytometry in the clinical laboratory. Principles, applications and problems. PMID- 1306963 TI - ["Advantages" and inconveniences. Apropos of breast implants]. PMID- 1306964 TI - [Forum: dermopigmentation or medical tattooing. History of tattooing]. AB - Tattooing has been performed all over the world since prehistoric times, as indicated by numerous ancient relics. The significance of tattoos has differed at times and in different civilisations (means of communication, social identification mark, religious origin). Today, it is performed by real artists who have inspired its medical applications. Medical dermopigmentation was initially used in the context of breast reconstruction (nipple areola complex) and, with subsequent refinements, its indications have been extended to the treatment of residual scars and to the permanent make-up. PMID- 1306965 TI - [Forum: dermopigmentation or medical tattooing. Needles and ink]. AB - Tattooing has been performed since ancient times. It has survived religions, development of education, wars and all forms of repression. Tattooing has gained a new lease of life at a time when this practice appeared to be dying out; why? In reality, tattooing corresponds to a need to be different, to make oneself attractive and to see oneself as a unique being and the age of uniformity in which we live is a very important factor for requests for dermography. Techniques have progressed together with conditions of asepsis and sterilisation. Until the profession of tattooist is officially recognised, it will always be associated with the idea of sordid techniques in makeshift quarters. The very survival of this artistic profession requires serious training and standards of hygiene. Failure to recognise this profession would result in its prohibition in the short term, leading to clandestine activity in which standards would obviously not be respected. PMID- 1306966 TI - [Forum: dermopigmentation or medical tattooing. Brief notes on technical aspects of dermopigmentation]. AB - Tattooing is a very old procedure widespread throughout the world. Recently dermatologists and plastic surgeons have applied this procedure for medical dermography. Incarcerating a pigment in the depth of the dermis has caused no problems for professionals and aestheticiens performing tattoos. Medical ethics oblige us to specify the nature of the pigment used. The instrument used for injecting the pigment should be well adapted for safety, technically, ergonomically and for asepsis. PMID- 1306967 TI - [Forum: dermopigmentation or medical tattooing. Dermopigmentation with an esthetic aim. Apropos of 420 cases]. AB - 420 cases of chromatic skin corrections for medical or aesthetic reasons have been documented over the last 1-5 years. The author analyses cases based on local anatomy classification, so that good and poor results of the technique are clearly revealed. Results are then regrouped in a synthetic study, without distinction of anatomical area. This synthesis establishes a check list of defects inherent in the technique: pain or discomfort, poor smoothing-out of skin defects, far from natural chromatic variations of the skin, dull lacklustre colours, short-lasting pigmentation, and chromatic instability of dyes. All these pigmentations were performed using basic techniques and medical pigments. The author suggests that in the future these defects should be corrected by: more systematic use of dyes used by tattoo artists, addition of a gloss in the dyes, transparent technique, anaesthetic skin cream. PMID- 1306968 TI - [Forum: dermopigmentation or medical tattooing. Dermopigmentation and reconstruction of the nipple-areola]. AB - The use of pigmented grafts for nipple-areola reconstruction of amputed breasts is disappointing because of frequent depigmentation. Dermopigmentation is an easy, quick and effective means to ensure restoration of the nipple-areolar complex. This technique is presented as a two-step reconstruction under local anesthesia, on an outpatient basis. The final nipple may be obtained, at the second stage, by silicone prosthesis implantation under the previously pigmented mammary skin. PMID- 1306969 TI - [Forum: dermopigmentation or medical tattooing. Dermography in cancerology. Apropos of 220 clinical cases]. AB - Based on a series of 220 cases of reconstruction (63 cases) or correction (67 cases) of the nipple-areolar complex and various extramammary procedures (tattoo scar revision, lips, eyebrows, eyelashes) (90 cases), the authors present their 2 year experience of medical dermography in a cancer centre. Dermography allows breast reconstruction to be completed in a large number of patients who had initially refused to complete their reconstruction. This minimally aggressive outpatient technique which reconstitutes the areolo-nipple complex with sufficient quality, is now part of reconstruction protocols and is gradually replacing surgical techniques. PMID- 1306970 TI - [Forum: dermopigmentation or medical tattooing. In practice ... how to perform medical tattooing?]. AB - Dermopigmentation is now part of the therapeutic armamentarium of plastic surgeons. In good indications and when applied according to a few simple rules, every surgeon can obtained reliable and reproducible results with medical dermography. This therapeutic procedure is performed on an outpatient basis, usually in several sessions; subsequent revisions are always possible provided certain basic errors are avoided. The authors describe each step of this technique. PMID- 1306972 TI - [Assembly of free osseous fragments in the treatment of injuries of the external orbital area]. AB - The good long term results obtained following the remodeling of the frontal bandeau in craniosynostosis have demonstrated the viability of large bony segments following total periosteal stripping. In this present study, this concept has been applied in the management of acute midfacial fractures and their sequelae. To try to answer the fundamental questions of how wide of an exposure is needed for the treatment of these fractures, how denuded can bone segments be and expect to survive, and above all, how frequently is primary bone grafting needed, the author resorts to the complete detachment and removal of the fractured segments and their reassembly on a side table. This, theoretically, accomplishes the following: the best exposure of fragments, the best anatomical reduction, an accurate assessment of segmental loss and the need for immediate bone grafting, a normal topographical reconstruction. Bone scans have indicated long term perfusion in every case in which they were obtained. Except in cases of post traumatic deformity correction, bone grafts were not needed. The free segment reassembly fractured facial bones is but one additional technique gained from craniofacial surgery. Much, however, remains to be learned about large free segment revascularization and healing. PMID- 1306971 TI - [Surgical treatment of myopathic ptosis. Apropos of 20 surgically treated cases]. AB - Twenty cases of severe progressive ophthalmoplegia (Myopathic ptosis) with significant ptosis were treated by various procedures, including levator resection with blepharoplasty or frontalis suspension using temporalis fascia. Surgical indications were generally limited to cases with poor or absent levator function. The results are analysed after an average follow-up of 6 months. The particular problems concerning surgery of myopathic ptosis are discussed. PMID- 1306973 TI - [Free radial antebrachial flap. A retrospective study of 48 cases. Practical applications]. AB - The authors have studied 48 chinese forearm free flaps operated since 1982 at St Louis, Hospital Paris. Analysis of early complications and failures shows that the few problems that occurred seem to involve hemodynamics more than technical problems. The results support the hemodynamic theory about radial forearm free flaps: low-flow flap which contrasts with the wide diameter of the radial artery. This kind of free flap may not support interpositional vein graft for arterial bridging (stasis, distension of the graft then thrombosis), which must be taken into account in the operating procedure. When the radial artery needs to be lengthened, we therefore systematically reduce the risk of thrombosis by re establishing radial artery outflow for safety: either by distal radial artery anastomosis, or with an arteriovenous shunt. PMID- 1306974 TI - ["Reposition-flap" technique in amputation of the finger tip. Apropos of a series of 21 cases]. AB - The authors review 21 cases of a so-called "reposition-flap" technique for finger tip injuries consisting of simple reposition when no vessels can be found for replantation. This technique is combined with palmar soft tissue excision and advancement of a local flap to cover the bone providing blood supply and good sensitivity. The mean age in the 19 patients was 34 years. The Weber test was an average of 6 mm in the 17 patients with more than 2 years of follow-up. A moderate nail hook deformity was noted in 24% and cold intolerance in 28.5%. PMID- 1306975 TI - [Treatment of incisional hernia of the abdominal wall by the skin lacing technique. Apropos of 30 cases]. AB - The treatment of large incisional hernias is often difficult, as reflected by the many surgical techniques proposed and the high recurrence rate. Since 1983, the authors have used a skin lacing procedure in these large hernias which frequently tend to recur. This report was based on the study of 30 consecutively patients operated by this method between 1983 and 1989. The objective results evaluated clinically in terms of the quality of the abdominal wall after more than two years of follow-up appear to argue in favour of this little known technique which combines simplicity, rapidity and reliability. Based on their experience, the authors believe that this method has a place in the therapeutic arsenal for abdominal wall repair as, in some cases, it can resolve the difficult problem of treatment of large, recurrent incisional hernias regardless of the patient's age. PMID- 1306976 TI - [Free-tissue transfer in plastic surgery (emergencies excluded). Apropos of a 10 year experience]. AB - Over a period of ten years the authors have performed 176 elective free tissue transfers. Flaps used were 99 latissimus dorsi, 46 chinese forearm flaps, 12 fibula, 6 toes, 5 omentum, 4 parascapular, and 4 others flaps. Recipient sites were lower limbs in 106 cases, head and neck in 50 cases, forearm and hand in 13 cases, thorax, abdomen, and buttocks in 7 cases. The overall failure rate was 5.7 per cent. Analysis of these failures taught us some original principles. Among these principles, the risk of vascular thrombosis is very important when a venous graft is performed on one end of the artery of a low blood flow flap such as chinese forearm or fibular flaps when the other end of this artery is ligated. When such a graft is done we think that the best way to avoid thrombosis is to suture the other end of the flap artery to a recipient vessel which can be even the distal end of the flap vein itself. Pretransfer expansion of a latissimus dorsi flap was successfully performed in 4 cases. Migrating semi-free flap method, in which the vascular pedicle of a flap is temporarily sutured to recipient vessels located far from the defect, was performed in 12 cases, in most cases on lower limbs where this method constitutes a modern variant of the cross leg. Folded free-flap method, in which a flap is folded on itself during some days before excision of the recipient site, was performed in 14 cases. Analysis of this series also allowed us to review in detail our usual strategic principles for vascular anastomoses in the head and lower limbs. PMID- 1306977 TI - [Microsurgical reconstruction of the mandible]. PMID- 1306978 TI - [Acute pancreatitis and lysosomal enzyme]. PMID- 1306979 TI - Effect of immunization with anti-idiotypic antibody to melanoma antigen on lung metastasis in mice. AB - To determine whether the pulmonary metastases of melanoma cells could be inhibited, C57BL/6 mice were immunized with an anti-idiotypic antibody, 7C4, corresponding to a mouse melanoma antigen. Three groups of mice were compared: 1) 7C4-immunized group which received an injection of 100 micrograms of 7C4 in Freund's complete adjuvant (FCA) subcutaneously on day -21 followed by intraperitoneal injections of the same dose on days -14 and -7,2) adjuvant treated control group administered with only FCA, and 3) untreated control group. On day 0, 5 x 10(5) of BL6 cells were injected into the caudal vein of all mice. Two weeks later, they were sacrificed and their lungs were removed. The number pulmonary metastatic colonies present on the lung surface were counted and compared among the groups. The length of survival days was also compared. The 7C4 immunized group showed an average of 166 +/- 44 colonies as compared to more than that of 300 colonies in each control groups, and a significant difference was observed (P < 0.01). The immunized group survived significantly longer than the control group (Greenwood's formulation) on day 23 (P < 0.01). Thus the immunization with 7C4 effectively inhibited lung metastasis of melanoma cells. These findings suggest that vaccination with anti-idiotypic antibody to tumor antigen is effective on inhibiting tumor metastasis. PMID- 1306980 TI - Combined therapy of a cephalosporin, Shiomarin and a new potent protease inhibitor, E3123 in rat taurocholate-induced pancreatitis. AB - The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin (SM) were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasemia, high amylase activity in ascitic fluid, and hyperendotoxemia and a high serum level of fibrin degradation products (FDP), redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and SM was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis. PMID- 1306981 TI - "Cocktail" therapy for acute pancreatitis: combined therapy of protease inhibitor, xanthine oxidase inhibitor and platelet activating factor antagonist in rat caerulein-induced pancreatis. AB - A supramaximal dose of caerulein (5 micrograms/kg.hr for 3.5 hours) caused an acute pancreatitis with marked hyperamylasemia and intense interstitial edema in rats. In this model of pancreatitis, the redistribution of lysosomal enzyme in acinar cells as well as the increased lysosomal and mitochondrial fragility were also observed. The combined therapy of a low molecular weight protease inhibitor, FOY, a synthetic platelet activating factor (PAF) antagonist, CV 6209, and a xanthine oxidase inhibitor, allopurinol produced more significant improvements in all the parameters examined than the therapy of any only one of these three agents, each only one therapy exerting a partial significant protective effect. These results indicate that several factors, such as unknown proteases activities, PAF and oxygen-derived free radicals may be involved in the pathogenesis of pancreatic injuries in this caerulein-induced pancreatitis. These results also suggest that such a combined therapy of different kinds of agents, whose therapeutic mechanisms are also different, is useful in the clinical treatment of acute pancreatitis. PMID- 1306982 TI - A new bioabsorbable material for rat vascular cuff anatomosis: establishment for the long-term orthotopic liver transplantation model. AB - Rat vascular anastomosis was performed using a newly synthesized bioabsorbable material (LA-GA copolymer) cuffs and the ordinary polyethylene cuffs. The LA-GA copolymer cuff which anastomosed the portal vein and the inferior vena cava were patent and developed no collateral veins even after 6 months, keeping the transplanted liver normal. By contrast, the polyethylene cuff anastomosed portal vein was completely occluded and the collateral veins were highly developed, with the transplanted liver showing the fatty degeneration of hepatocytes and numerous regenerative nodules. It is concluded that the LA-GA copolymer cuff is a suitable material for the short and long term study of rat orthotopic liver transplantation. PMID- 1306983 TI - The influence of parathyroid hormone-related protein on hepatic IGF-1 production. AB - Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery. Electromagnetic blood flow probes in the portal vein and hepatic artery allowed continuous measurement of hepatic IGF-1 production. In accordance with a latin square design these calves received iv mesenteric infusion (for 60 min) of calcium (Ca, 0.125 mmol.kg body wt-1), the synthetic human parathyroid hormone related protein (1-34) fragment (PTHrP, 1 nmol.kg body wt-1), the synthetic analogue [tyr]34-bovine PTH-(7-34) NH2 (2 nmol.kg body wt-1) and PTHrP (1 nmol.kg body wt-1) or solvent alone (1.2 ml.kg body wt-1). Hypercalcaemia observed following Ca infusion had no significant effect on hepatic IGF-1 production. PTHrP induced a slight but significant increase in plasma Ca and IGF-1 concentrations measured in the hepatic vein, without changing blood flows measured in the hepatic artery and portal vein. Thus PTHrP increased hepatic IGF 1 production (15.1 +/- 2.7 nmol.6 h-1.kg body wt-1 vs 4 +/- 1.3 nmol.6 h-1.kg body wt-1 in controls; p less than 0.05). These effects induced by PTHrP were inhibited by the synthetic analogue [tyr]34-bPTH-(7-34) NH2. PMID- 1306984 TI - Human parathyroid hormone-related peptide-(107-111) does not inhibit bone resorption in neonatal mouse calvariae. AB - Recent analysis of the structure-function relationship of human PTH-related peptide (hPTHrP) has led to the discovery that its direct inhibitory activity on osteoclastic bone resorption resides fully in the 107-111 sequence of the peptide, as assessed by a bone resorption assay using isolated rat osteoclasts. Here we report that hPTHrP-(107-111) is inactive in neonatal mouse calvariae in culture. hPTHrP-(107-111), at doses of 10(-12)-10(-6) M and incubation periods up to 96 h, did not affect either basal or agonist-stimulated 45Ca release from prelabeled neonatal mouse calvariae, while salmon calcitonin was a potent and powerful inhibitor of both basal and stimulated 45Ca release from bone. Moreover, salmon calcitonin, but not hPTHrP-(107-111), inhibited the increase in osteoclast number in hPTHrP-(1-34)-treated bones. Furthermore, hPTHrP-(107-139) also failed to inhibit 45Ca release and the hPTHrP-(1-34)-induced increase in osteoclast number in this organ culture model when tested under conditions identical to those for hPTHrP-(107-111). The addition of indomethacin to hPTHrP-(107-111)- or hPTHrP-(107-139)-treated bones was without effect, excluding the possibility that the direct inhibitory activity of these peptides on osteoclasts is ablated by a prostaglandin-mediated mechanism. Although the mechanism underlying the apparent inability of the carboxyl-terminal PTHrP fragments to inhibit osteoclastic bone resorption in neonatal mouse calvariae is unknown, it may involve the complex microenvironment of osteoclasts in intact bone, which contains a large variety of cell types other than osteoclasts. PMID- 1306985 TI - [Chagasic infection in blood donors from hospitals in endemic regions of Chile (1982-1987). Epidemiological impact of the problem]. AB - Chagas' disease, produced by Trypanosoma cruzi and transmitted by hematophagous triatomine bugs, exists in the Western Hemisphere from the south-western United States to central Chile and Argentina. It exists in rural and periurban sections of the northern half of Chile, with a prevalence of 16.9%. Constant rural-urban migrations have contributed to its spreading to urban sections. In order to investigate the impact of these migrations on the population susceptible of being blood donors and the probable increasing of the risk of T. cruzi transmission by blood transfusion, epidemiological surveys were carried out in donors from 22 hospitals located in the northern half of Chile. By means of an indirect hemagglutination test for Chagas' disease 16,841 blood donors were examined, arising a 2.7% of positivity, percentage that permitted to estimate that 126,477 potential blood donors infected with T. cruzi should be in the urban sections studied. These facts strengthen the need that serology for Chagas' disease must be routinely performed in endemic regions of the country, to adopt or reinforce the pertinent preventive measures. PMID- 1306986 TI - [Serologic longitudinal follow-up of surgically treated patients for hydatidosis]. AB - Beginning with the register of human hydatidosis cases, kept by hydatidosis struggle programs of Rio Negro Province, was done the serologic longitudinal follow-up in patients operated on in the period 1980-1987, in the influence area of Ingeniero Jacobacci, Rio Negro, Argentina. The local Supervision Program obtained blood samples of 36 patients during 1990 (59% of them were operated on in the considered period), five patients died corresponding the remaining to persons to whom did not live in Ingeniero Jacobacci or to whom were not possible to evaluate. The blood samples were studied by DD5, confirming the disease immunologically in 18 cases (50%). In this work are evaluated possible causes of reinfection: surgery technic, individual susceptibility, immunological factors. PMID- 1306988 TI - Primary health care in parasitic diseases. PMID- 1306987 TI - [New metacercariae of the genus Tylodelphys (Trematoda, Diplostomatidae) in lacustrine populations of Galaxias maculatus (Teleostei, Galaxiidae)]. AB - Metacercariae of three new species of Tylodelphys (Trematoda, Diplostomatidae) were found in the brain of Galaxias maculatus (Teleostei, Galaxiidae), at the Meliquina Lake, Neuquen Province, Argentina. These metacercariae are morphologically described as Tylodelphys argentinus n. sp., Tylodelphys barilochensis n. sp. and Tylodelphys crubensis n. sp. This is the first time that a stage of genus Tylodelphys is mentioned parasitizing Galaxias maculatus. Metacercariae of T. barilochen sis n. sp. were also found in G. maculatus brain at the Perito Moreno Lake, Rio Negro Province, Argentina. PMID- 1306989 TI - Porrocaecum muraenesoxi n. sp. (Nematoda: Heterocheilidae) from the intestine of marine eel fish Muraenesox talabonoides (Bleeker). AB - A new species of the nematode genus Porrocaecum Railliet et Henry, 1912 obtained from the marine eel fish Muraenesox talabonoides (Bleeker) from Kakinada (Andhra Pradesh) is described. The specimens do not agree with the description of known species of the genus Porrocaecum, hence a new species Porrocaecum muraenesoxi has been established to describe these nematodes. The new species is distinguished by body size, location of nerve ring, length of intestinal caecum, number and arrangement of caudal papillae, spicules length, and tail conical in both sexes. Rectal glands present. PMID- 1306991 TI - [Epidemiological and diagnostic aspects of human Cryptosporidiosis in Chile]. AB - Cryptosporidium sp. infections have been reported in different Chilean localities, both in healthy individuals and immunocompromised patients. Among the first, hospitalized and ambulatory children less than 3 years old are the age group more affected reaching frequencies from 3.1 up to 19.3%. In pre-school children, school children and adults the prevalence rates have been 1.1, 0.2 and 0.3% respectively. According to the epidemiological studies carried out, the routine laboratory diagnosis of this parasitosis should be emphasized in the parasitological stool examinations in children under 3 years of age, and selectively in the older ones. PMID- 1306990 TI - [Histotropism and pathogenicity of Trypanosoma cruzi in albino mice (NHI) isolated from triatomines in Nuevo Leon, Mexico]. AB - The neolonese strain of Trypanosoma cruzi was obtained from deyections of nosed bugs (Triatoma gerstaeckeri) which were caught in General Teran and Dr. Coss, Nuevo Leon. This strain was kept alive for passing it from mouse-triatomines and vice versa. Posteriorly, nests of amastigotes were found in skeletal and myocardial muscle fibers from albinous mouse Mus musculus NHI by using light microscopy and electron microscopy. In consequence, the parasitic element was classified as a myotropic strain, although it was observed in less amount in liver, kidney and spleen. Main pathological changes observed were intersticial inflammation, disruption of muscle fibers, myocarditis, mitochondrial alteration and cytoplasmic vacuolation. PMID- 1306992 TI - [Oral elimination of strobila segments of Taenia saginata]. AB - Within a 14-24 hours lapse after gynecological operative surgery, a 27-year-old woman eliminated with vomit two large taperworm pieces, measuring 3 and 2 meters respectively. At the laboratory they were identified as Taenia saginata strobila with immature, mature and gravid proglottids. The patient informed that she liked to eat raw beef. Treatment consisted in a single dose of praziquantel: 15 mg/kg body weight. Parasitological controls (two series of three fecal samples each), performed three months later, resulted negative for Taenia eggs. PMID- 1306993 TI - [Laboratory study on the immediate and persistent insecticide activity of the pyrethroid lambda-cyhalothrin on nymphs of IV instar Triatoma infestans]. AB - Lambda-cyhalothrin (LCT) is a new broad-spectrum synthetic pyrethroid insecticide with efficient immediate and persistent activity against a great variety of arthropods harmful both to human and animal health and to vegetal production. In many countries this insecticide has been successfully used in the control of infectious diseases vectors, such as mosquitoes, triatomine bugs (transmitters of Trypanosoma cruzi, agent of Chagas' disease) and other arthropods. In order to test the immediate and persistent activity of LCT under laboratory conditions (27 degrees C and 75-80% humidity) on laboratory reared Triatoma infestans--the most resistant instar of this insect to the commonest insecticides used--a series of six experiments was performed in 1-year period. Previous to experiments, the interior surface (400 cm2) of 36 specially manufactured cardboard boxes was uniformly sprayed with 2 ml of the following substrates: 12 with 0.6% LCT suspension, 12 with 1.0% LCT suspension and 12 with water (controls). Twenty four hours, 30 - 90 - 150 - 270 and 360 days later, in two pairs of each six boxes, lots of 10 T. infestans IV nymphs were deposited inside of them. In each of the six experiments, daily observations of the conditions of the insects (unaffected, affected in terms of various grades of progressive uncoordination, or dead) after exposure to the insecticide were performed to end with the register of these conditions 96 hours later. Moreover, after 7 and 10 days of exposure in the immediate and persistent effect of LCT respectively a 100% of mortality was verified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1306994 TI - Description of a new species of Kathlania Lane, 1914 (Nematoda: Cosmocercidae) from the intestine of the marine fish Trichiurus muticus (Griffith). AB - Kathlania sprentii n. sp. is described from the intestine of a marine fish. Trichiurus muticus (Griffith) from the South coast of Indian Ocean, India. The new form differs from other known species of the genus in the presence of two rounded teeth-like structures in the buccal capsule, spicule ratio 1:4 and rod shaped gubernaculum with bifurcated distal end. PMID- 1306995 TI - Importance of the control of intestinal parasitoses. PMID- 1306996 TI - [Current status of knowledge on Chagas' disease in the Mexican Republic]. AB - A thorough review of the medical literature is made regarding Chagas' disease in Mexico and elsewhere since 1939, when Trypanosoma cruzi was first reported in this country, until 1991. The location where human cases, non human reservoirs and vectors have been found and are pointed out by means of tables and charts. Comments are made regarding the results reported. The importance of increasing the studies of Chagas' disease in Mexican Republic is stressed. PMID- 1306997 TI - [First report on Neotoma micropus (Rodentia) as a reservoir of Trypanosoma cruzi in Mexico]. AB - Using xenodiagnosis, two (8.0%) of 25 woodrats Neotoma micropus were found infected with tripanosome parasite in Vaquerias, a village in Nuevo Leon State, Mexico. The triatomine species developing infective metacyclic trypanosomes at week 12th were Triatoma pallidipennis, T. infestans and T. gerstaeckeri. Experimental infections using infected dejections were successfully conducted on laboratory mice (CD1 strain) confirming the vertebrate cycle of Trypanosome cruzi. The biological characterization of T. cruzi strains was demonstrated based on: 1) Triatomine developmental cycle. 2) A vertebrate host parasitic period up to 25-33 post-infection days, and. 3) Typical morphology of bloodstream trypomastigotes and amastigotes from myocardial nest. This is the first report of T. cruzi biologically characterized in Nuevo Leon, as well as a new report of N. micropus, increasing the list of reservoir hosts in Mexico. PMID- 1306998 TI - [Intestinal amebiasis in Antofagasta, Chile]. AB - In January 1989--December 1991 period we verified 35 cases of symptomatic intestinal amebiasis in Antofagasta, the main city of the North of Chile. Out of the total number of studied patients 23 were adults (77.1% males and 22.9% females) and all of them were permanent residents of Antofagasta. E.histolytica was frequently detected in association with other parasites and/or commensals, and observed alone in only seven cases. The clinical and epidemiological aspects of these 35 cases are discussed. PMID- 1306999 TI - Intraperitoneal reaction in Wistar rats after inoculation with several components of a human hydatid cyst. AB - Fifteen male Wistar rats were inoculated intra peritoneally with material obtained from a human hepatic hydatid cyst with 20% viability and previously inactivated with 20% NaCl. When the animals were sacrificed six months later, hydatid granulomas surrounding parasitic remains were detected in the peritoneum. PMID- 1307000 TI - [Histopathology of Kingiella chilenica (bivalvia, cyamiidae) parasitized by rediae and cercariae of the Gymnophallidae family]. AB - Gonadal and digestive gland tissues of Kingiella chilenica specimens, which were infected with trematode larvae, were examined to determine the organs that are normally invaded by these parasites. Rediae containing cercariae of this digenetic trematod, appeared exclusively restricted to the tissues of the digestive gland. Consequently, no damage or alterations were observed in the gonad or other related tissues of the infected specimens. This, linked to the fact that parasitized females may also appear with brooded embryos, supports the conclusion that the reproductive activities of the bivalve mollusc are not affected by the presence of these infecting larvae. PMID- 1307001 TI - [A case of massive ascariasis in the riverside sector of the Rinihue lake, Chile]. AB - A case of massive ascariasis in a three and a half years old girl who eliminated 104 worms after treatment with mebendazole is reported from a riverside sector of Rinihue Lake, Chile. Chilean literature about intestinal massive ascariasis is reviewed. Worms showed 12-29 cm of length and 0.2-5.5 g of weight. Total worms weighted 155.8 g. PMID- 1307002 TI - [Clinical considerations on 2 cases of hepatic fascioliasis. Importance of the imaging examinations]. AB - Two cases of hepatic human fascioliasis, both with antecedents of eating watercress, hepatobiliary symptoms and high eosinophilia are described. In the first one (42 year-old male), at the beginning the abdominal ecotomographical and computed tomography images suggested an hepatic tumor, but afterwards, the finding of Fasciola hepatica ova in feces and the observation of numerous typical images of the fluke in the choledochus by means of an endoscopic cholangiography, plus lesions related to a Loffler syndrome detected in a chest radiography, lead to the diagnosis of hepatic fascioliasis. The patient was treated with dehydroemetine. In the second case (52 year-old male), presented pain in the upper right abdominal quadrant; in an abdominal ecography three cystic lesions in the right liver lobe were found. Nor in the feces neither in the bile F. hepatica eggs were observed. Serological tests for fascioliasis and hydatidosis resulted positive. The endoscopic cholangiography was normal. With the presumptive diagnosis of fascioliasis the patient was treated with dehydroemetine. But as his disturbances remained during the following six months, and raising the possibility of a suppurated hydatid cyst or hepatic abscesses, he was submitted to surgery, finding F. hepatica eggs in the chocolate-like hematic liquid. In the wall and in a liver mass resected a grunuloma with eggs of the parasite was detected. The patient was treated again and cured with dehydroemetine. The existence of subcapsular hematomata and granulomas in hepatic fascioliasis, which can give raise to a diagnosis confusion due to their aspect in the ecotomography and computed tomography are commented. The cholangiographic aspect of the affection is discussed. PMID- 1307003 TI - [Usefulness of the ELISA-IgG test in sera and filter paper blood eluates in the Chagas disease immunodiagnosis]. AB - An ELISA-IgG test using a soluble extract of Trypanosoma cruzi antigen has been developed. One hundred and seventy eight sera (74 healthy people, 44 chagasic patients with positive xenodiagnosis and 60 with clinical symptoms), and 64 paper filter blood eluates (35 healthy people, 10 chagasic patients and 19 with clinical symptoms) were tested by ELISA-IgG and an indirect hemagglutination test. Both types of methods presented an overall average concordance of 98.3% and 100.0% with sera and filter paper blood eluates respectively. A cut off (average of optical density plus 3 standard deviations) of 0.365 and 0.379 for sera and eluates was found. The use of ELISA-IgG in Chagas' disease clinical diagnosis and seroepidemiological studies is discussed. PMID- 1307004 TI - [Absorption of human serum antibodies against Toxoplasma gondii using Tachyzoites from the RH strain]. AB - Absorption experiments to determine the number of T. gondii tachyzoites to extract the anti-Toxoplasma antibodies present in the human serum were carried out. The antibodies titer from each serum (n = 4) was determined by means of the Sabin-Feldman test (dye test). Ten millions of tachyzoites were sufficient to absorb the antibodies from sera presenting titer 1:16, 1:64 and 1:256. On the other side, the absorption of a 1:512 positive serum with 10 x 10(6) T. gondii decreased the titer to 1:64 and the dye test became negative when using 50 x 10(6) tachyzoites. PMID- 1307006 TI - [Current prevalence of trichinosis in Santiago, Chile (1992). A study on 500 corpses]. AB - In August-December 1992, 500 diaphragm muscle samples taken at random from people who were autopsied at the Santiago Medico-Legal Service, were submitted to phototrichinoscopy to search for encysted larvae of Trichinella spiralis. For each sample seven small pieces were examined. Three hundred and eighty nine (77.8%) cadavers corresponded to males and one hundred and eleven (22.2%) to females. Ages ranged from 1 to 90 years. Ten (2.0%) of the individuals examined resulted positive, the higher frequencies corresponding to individuals over 20 years of age. The prevalence rate of T. spiralis infection found is rather similar to those detected in 1966-1967, 1972 and 1982, with percentages of 2.2, 3.4 and 2.8 respectively. PMID- 1307005 TI - [Electrocardiographic alterations in persons with a positive serology for toxoplasmosis]. AB - To each of 11,161 randomly taken people from urban and peri-urban localities of the first seven regions of Chile (geographic area of distribution of Chagas' disease in the country), with negative serology for Chagas' disease, an indirect hemagglutination test (IHAT) for toxoplasmosis and an EKG were practiced. The IHAT for toxoplasmosis resulted positive in 3,519 individuals (31.5%). The EKG showed alterations in 10.9% of the IHAT positive individuals and in 7.9% of the IHAT negative ones. This difference between the proportion of altered EKG in IHAT positive people and altered EKG in those with negative IHAT is statistically significative with p < 0.001. These results suggest the convenience of considering toxoplasmosis as a cause of chronic myocardiopathy in epidemiological studies on Chagas' disease, since not discard the presence of Toxoplasma gondii infection should overvaluete the magnitude of the impact of Trypanosoma cruzi in the genesis of such a myocardiopathy. PMID- 1307007 TI - Using a computer color-matching system in color reproduction of porcelain restorations. Part 1: Application of CCM to the opaque layer. AB - The reproduction of natural tooth color using porcelain restorations is quite cumbersome, for it is difficult to select, communicate, reproduce, and evaluate color objectively. The present process of color reproduction lacks precision and is primarily dependent on the individual efforts and abilities of the dentist and ceramist. The computer color-matching system, aided by a spectrophotometer and computer, can be an excellent method for reproducing specific colors of various objects. This paper reports application of the system to reproduce various opaque colors used for metal ceramic restorations. PMID- 1307008 TI - Shear bond strength of textured opaque porcelain. AB - Textured opaque porcelains have been introduced to improve the appearance of metal ceramic restorations by increasing light refraction. This investigation compared the shear bond strength of a textured opaque porcelain with that of a conventional opaque porcelain. Opaque and body porcelains were fired onto six different alloys and the specimens were loaded to failure by applying shear force at the alloy-porcelain interface. No significant differences in bond strength were found between the textured and conventional opaque porcelains for any of the alloys tested. PMID- 1307009 TI - Differences in color between fired porcelain and shade guides. AB - The inaccuracy of premixed porcelain shades may cause errors when color matching porcelain crowns. Most brands of porcelain are labeled to match shades of the Vita shade guide, but produce slightly different colors from this guide upon firing. The purpose of this study was to quantify in CIE delta E* units the color differences between the Vita shade guide colors and four commercial porcelains for metal ceramic crowns. Two operators prepared shade-guide teeth from six shades of four brands of porcelain. Opaque, body, and incisal layers were fired in the form of shade-guide teeth on Vita ceramic carriers used for making custom shade-guide teeth. The colors of these teeth were measured with a Beckman spectrophotometer with an integrating sphere. The average delta E* values for the differences between the colors of the Vita shade guide and the fired porcelains for each of the brands were 3.1, 2.9, 4.1, and 2.0, respectively, for the first operator and 4.1, 2.6, 2.8, and 1.6, respectively, for the second operator. The color difference between the custom shade-guide teeth and the Vita master shade guide were significantly affected by both brands and shades. The overall average error resulting from the differences in colors between the Vita shade guide and fired porcelains was 3.0 for the first operator and 2.8 for the second operator. The mean delta E* between the teeth prepared by the two operators was 3.6. The color difference between the teeth made by the two operators was not significantly affected by brands or shades. PMID- 1307010 TI - Comparisons of tactile thresholds between implant-supported fixed partial dentures and removable partial dentures. AB - This study compared the tactile sensitivity of splinted abutment and denture teeth of 16 fixed partial dentures (FPD) supported by blade implants and 16 removable partial dentures (RPD) in patients with Kennedy Class I and Class II edentulous conditions. No significant differences were noted between the tactile thresholds of the natural abutment teeth and artificial teeth in the FPD and RPD groups. The splinted abutment teeth required 45.4 g, or 5.4 to 5.8 times higher occlusal loads than did those needed for the comparable nonsplinted teeth, to detect the stimulus. A further increase of 54% in thresholds with the FPD and over 100% with the placement of the RPD indicated the superiority of the RPD in terms of load distribution as a result of the cross-arch splinting and mucosal support. Moderate positive correlations (r = 0.37 to 0.46; P < .05) between tactile thresholds and masticatory performance were found, signifying that reduced tactile perception was not responsible for the incomplete restoration of the masticatory function with RPDs or FPDs but might be contributing to increased masticatory performance within both treatment groups. PMID- 1307011 TI - The effect of polishing porcelain laminates on induced I-Bar wear. AB - Partial-coverage porcelain laminate restorations may successfully be used to create undercuts for removable partial denture abutment teeth. If recontouring of such restorations becomes necessary after placement, surface polishing would be necessary prior to removable partial denture fabrication. In this study the wear of luted porcelain laminates, which received a polished surface treatment and contacting I-bar clasps, was quantified over a simulated 2-year period when subjected to removable partial denture placement and removal. Scanning electron photomicrographs and computer imaging were used for wear measurement. These data were compared to previously recorded data on wear of I-bar tips against human enamel and glazed, luted, porcelain-laminate restorations under the same experimental conditions. No measurable wear was observed on any of the laminate specimens. I-bar clasps tested against the glazed laminate restorations exhibited the greatest mean wear, and those tested against the polished laminates exhibited the least mean wear. PMID- 1307012 TI - Patients with atrophic mandibles: opinions regarding the benefit of preprosthetic surgery. AB - This paper follows a previous report of an investigation regarding treatment of patients having atrophic mandibles. These patients either had surgery and received new dentures or received new dentures only. This paper reports the opinions of the patients concerning their treatment after an average of 6.5 years. The results showed that the patients in the group with atrophic mandibular ridges that were surgically treated were more generally satisfied with their dentures in comparison with the group of patients with atrophic ridges that were not surgically treated. The attitudes of the latter did not differ from the control group of patients having normal ridges. PMID- 1307013 TI - Clinical evaluation of resin-bonded prostheses. AB - Resin-bonded prostheses were clinically evaluated following a mean period of 41 months. The abutment teeth were minimally prepared, and one groove was placed on the surface approximating the edentulous space. Retainers were treated using the Silicoater technique. Thirty-four prostheses were made for 32 patients. Four patients were lost from the study and 30 units were re-examined. Two prostheses had debonded. The results suggest that resin-bonded prostheses can be successful if meticulous attention is given to the procedures outlined. PMID- 1307014 TI - Accuracy of the acrylic resin pattern for the implant-retained prosthesis. AB - An in vitro study was conducted to determine the accuracy of fit of the acrylic resin pattern for the implant-supported prosthesis to the implant abutments. A master model containing five Nobelpharma titanium implants was fabricated using Ivocap acrylic resin. Using this model, five standardized acrylic resin patterns were fabricated from the three test dental acrylic resins. The fabricated patterns remained on the master model for 24 hours before removal and subsequent measurement. To compute the accuracy of each pattern, three special measuring points were firmly attached to each gold cylinder prior to pattern fabrication and the x, y, and z coordinates of these measuring points were determined. Measurements were made prior to pattern fabrication, with the cylinders on their respective abutments and after pattern fabrication, when the pattern had been removed from the master model. The results of this study showed that there was a significant difference in accuracy between the test acrylic resins and that none of these materials was completely accurate. PMID- 1307015 TI - The effect of crown length on the fracture resistance of posterior porcelain and glass-ceramic crowns. AB - This in vitro study measured the changes in the fracture resistance of posterior crowns as a function of crown length. The crowns, 10 for each group, were made of a feldspathic porcelain (Ceramco), a glass-ceramic material (Dicor), and an alumina-reinforced glass (In-Ceram). Three different crown lengths were tested on acrylic resin dies. The restorations were fractured in a testing machine using a steel ball, 12.7 mm in diameter, that contacted the occlusal surface at three distinct points. Statistical analysis was performed using the Weibull distribution. The fracture resistance increased significantly with increasing crown length for all crown materials. PMID- 1307017 TI - A philosophy of dental practice. PMID- 1307016 TI - The cytotoxic effects of denture base resin sealants. AB - Previous studies have shown that light-polymerized denture base resins have a cytotoxic effect on oral epithelial cells. The purpose of this in vitro study was to examine the effects of two denture base resin sealants when used on three light-polymerized denture base resins. Sample disks were examined for their effect on protein synthesis. Results indicate that one sealant protected the cells against toxic effects of the materials (P < .05), while one sealant enhanced toxicity up to 88% above that attributed to the resin alone. PMID- 1307018 TI - Estimation of parameters of allometric equations. AB - Accurate parameter estimation of allometric equations is a question of considerable interest. Various techniques that address this problem exist. In this paper it is assumed that the measured values are normally distributed and a maximum likelihood estimation approach is used. The computations involved in this procedure are reducible to relatively simple forms, and an efficient numerical algorithm is used. A listing of the computer program is included as an appendix. PMID- 1307019 TI - Study of lipid changes in freeze-dried fish during storage. I. The interaction of relative humidity and tissue lipids. AB - Several studies on lipid stability of freeze-dried fish pointed out the relationship between relative humidity (RH) and autoxidation of highly unsaturated fatty acids. The present study shows the changes of tissue lipids in two different fish, freeze-dried and stored under various RH conditions. Fillets of Scomber scomber L and Sardina pilchardus sardina were freeze-dried and stored for 1, 3, 6 and 9 months. periodically, the sample of both fish were analyzed to evaluate the autoxidation of lipids. The results show that the autoxidation of lipids is quicker during 1st-3rd month of storage, while in a high humidity environment the tissue lipids change slower. According to these results both time of storage and relative humidity must be controlled to maintain the nutritive value of freeze-dried fish. PMID- 1307020 TI - [Characterization of plasma glycosaminoglycans in hemodialysis patients]. AB - Glycosaminoglycans are heteropolysaccharides composed of disaccharide repeating subunits, each one containing a uronic acid component (glucuronic or iduronic acid) and a hexosamine (N-acetyl-glucosamine or N-acetyl-galactosamine, which may be differently sulphated). The presence of GAGs in human plasma has been demonstrated in several studies; they are bound to plasma proteins through non covalent linkages. However, very little is known about either their origin or their physiological role. Due to their anionic charge, they may influence some metabolic processes, such as blood coagulation, and they could also have a role in urolithiasis and atherogenesis. Moreover, they may be important in modulating the metabolism of some lipoproteins by affecting the rate of their catabolism. Modifications of GAG pattern have been described in a few pathological conditions such as mucopolysaccharidosis, connective tissue diseases and kidney diseases. A high frequency of accelerated atherosclerosis has been observed in haemodialysis patients (HD), probably associated with the altered lipoprotein profile, which is often described in these subjects. Since GAGs may play a role in lipoprotein metabolism, we isolated and characterized plasma GAGs from a group of HD patients and a group of normal matched subjects. Quantitative analysis of plasma GAGs showed a significant increase of these polysaccharides in the HD group. Circulating levels of GAGs were 8.21 +/- 1.89 micrograms/ml in control subjects, and 15.08 +/- 3.13 micrograms/ml in the HD group (p < 0.0001). The isolation of plasma GAGs by ion-exchange chromatography produced two uronic acid containing families: a low-charge (peak I) and a high-charge (peak II) species. Both of these contained GAGs associated with plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307021 TI - [Lipid and lipoprotein profile in psoriasis]. AB - Psoriasis is a common relapsing dermatosis characterized by an increased epidermal cell proliferation. In this work we studied the lipid and lipoprotein pattern in 17 patients affected by long-standing psoriasis and in 20 normal controls. Total cholesterol, triglyceride, HDL-cholesterol and Apolipoprotein AI and B levels were measured; VLDL, LDL and HDL chemical composition was assessed by preparative ultracentrifugation. Plasma lipid and lipoprotein levels were significantly lower in the patient group; chemical analysis of the main lipoprotein classes showed compositional abnormalities consistent with an accelerated turnover of these particles. We believe that epidermal cell proliferation can play a role in determining these changes. PMID- 1307022 TI - [Evaluation of an immunoenzymatic method for determining TSH and establishment of reference values]. AB - In the present work we reported the results of the valuation of IMx Ultrasensitive hTSH assay which is a Microparticle Enzyme ImmunoAssay (MEIA) for quantitative determination of human stimulating hormone (hTSH) in the human serum or plasma. We have determined the method's precision, within run and between run, sensitivity and recovery. This method has been compared with another one (Immuno RadioMetric Assay). Also reference values have been calculated in the "normal" male and female population and shortly commented. PMID- 1307023 TI - Comparison of three different methods for evaluation of Helicobacter pylori (H.P.) in human dental plaque. AB - Helicobacter pylori (H.p.) is a microorganism involved in peptic ulcer disease. To clarify the role of human dental plaque as a reservoir of H.p. and to compare different methods of investigation the authors studied 20 patients, 17 males main age 56 +/- 12 and 3 females 52 +/- 7, gastro-duodenal H.p. positive. The trial was carried out by cultural, biochemical and microscopical plaque analysis. Cultural and microscopical method were H.p. positive in 80% patients, urease in 100%, alkaline phosphatase in 80%, gamma glutamyltransferase in 70%, nitrate in 70%. To minimize the possibility of false results in H.p. plaque analysis it is necessary to use the three methods simultaneously. Further trials both on human plaque and on food and beverages will be useful to clarify the role of H.p. in human pathology. PMID- 1307024 TI - [Tubo-ovarian transplantation in the treatment of sterility. Experimental research]. AB - Microsurgical transposition of fallopian tube and ovary has the potential of being an efficient therapeutic treatment in patients with tubal sterility. The Authors present their experience of microsurgical adnexal transplantation in rabbit by two different techniques: the first procedure by microvascular anastomosis of the ovarian vessels, the second one without vascular pedicle. Function is evaluated at various time after grafting by: exploratory laparotomy on day 30 to establish whether circulation to the grafts was still maintained; macroscopic and microscopic examination of ovaries and fallopian tubes. The microvascular techniques prove highly reliable in terms of immediate vascular patency rate but it is disappointing that 50% of the autografts has failed with blocked vessels by day 30. Perhaps this is due to the difficult techniques in anastomosing the ovarian vessels of small caliber. In spite of these outcomes the vascularized autografts were viable and functional after transplantation in contrast with the non-vascularized tubo-ovarian grafts which all failed. This experience encourages to believe that the microsurgical technique could be employed for homograft transplantation in woman with extensive ovarian and tubal damages. PMID- 1307025 TI - [Action of retinol on viable cell recovery and clonogenic potential of HTC cells after in vitro hyperthermia]. AB - The aim of this study was to investigate if the association of both hyperthermic and Retinol treatment of HTC hepatoma cells could be useful in antitumor therapy. Treatment with 5 microM Retinol was carried out before or after hyperthermia (42 degrees C or 44 degrees C, one hour; in the latter case it was performed in cells already thermo-selected. We took into consideration two parameters, i.e. the number of the collected vital cells (evaluated by the trypan blue-exclusion test) and the clonal efficiency of these cells (calculated as number of colonies obtained from 250 cells cultured for 5 days). Thermal treatment alone caused a decrease of the number of the collected vital cells and of their clonal efficiency only in the cell cultures incubated at 44 degrees C. Instead the control thermo-selected cells, both at 42 degrees C and at 44 degrees C, showed both decreased clonal efficiency and yield of the vital cells. Compared with the control cultures treated with 0.1% Ethanol, used as vitamin A solvent, only cell cultures treated with Retinol before hyperthermia showed a decreased number of collected viable cells, nevertheless their clonal efficiency was unchanged. PMID- 1307026 TI - [Effect of hyperthermia and retinol treatment in vitro on HTC cell adhesiveness to laminin and fibronectin]. AB - Since cell adhesiveness is very important in the metastatic process and because both hyperthermia and treatment with Retinol can modify the fluidity of the lipid components of the plasma membrane (and therefore its receptor distribution), we investigated if a hyperthermic treatment (at 42 degrees C or 44 degrees C, for one hour) of HTC hepatoma cells, preceded or followed by treatment with 5 microM Retinol, could alter cell adhesiveness to Laminin or to Fibronectin-coated substrata. Hepatoma cells, after such treatments, were collected and processed by Auerbach's method. In the control cells thermal treatment alone caused a decrease of adhesiveness to Laminin but no change in that to Fibronectin. When treatment with Retinol was carried out before hyperthermia, the cells showed an increased adhesiveness to Laminin and a decreased adhesiveness to Fibronectin. Instead, when treatment with Retinol was performed in cells previously thermo-selected, a decrease of adhesiveness to both tested ligands was observed. PMID- 1307027 TI - [Human social activity under conditions of relative social isolation]. AB - The differences in using a "social isolation" concept in the psychological literature are presented. The term of "relative social isolation" is clarified. A relationship between human adaptation to the relative social isolation environments and the development of his social qualities and social activities is presented. The "social context", dictating motivation attitudes of a man to the isolation situation, emotional experiences, self-appraisal of activity is of crucial importance for evaluating the real environments of relative social isolations. Social activity of a personality is studied as the relations of a man with the conditions of his activity. The results of studying the dynamics of the psychic state of a man during individual and group isolation are compared. It is concluded that social activity of man and his functional state are interrelated. The particular manifestations and direction of the changes in the social activity of the subject depend on the duration of isolation and are determined first of all by social significance and meaningful and balanced work for a person as well as by the amount and frequency of direct and mediated social contacts under specific conditions of relative social isolation. PMID- 1307028 TI - [The prediction of the work capacity of flight operators with different levels of anxiety]. AB - It was shown that due to a high body reserve potential the fatigue in low anxious flight operators (LA) occurs only by the 5th-6th post-leave months and in highly anxious flight operators (HA) it develops already by the 3rd post-leave month. Such pattern of developing the fatigue in flight operators enables one to conclude that the "critical months" for flight safety can be the 3rd and 5th post leave months in HA and LA flight operators, respectively. It is just these months during which the flight operators should be rehabilitated at the preventorium. The recovered body reserves are determined from such criteria as the return of working capacity (based on correction test data), arterial hemodynamics and especially erythrocytes resistance to the baseline levels during the first post leave month. PMID- 1307029 TI - [The use of the optimal control method for correcting lipid metabolism]. AB - The paper discusses an optimal artificial control of lipid metabolism which is the most important element of human life. The fact that the solution of this problem contributes to a decrease in risk of developing some diseases in the pilots and cosmonauts and an increase in human adaptive potentialities is particularly emphasized. An approximated algorithm of solving an assigned model problem and the results of computational experiments are presented. PMID- 1307030 TI - [Bone mineral density in cosmonauts after flights lasting 4.5-6 months on the Mir orbital station]. AB - A technique of quantitative digital roentgenography (QDR) being a current modification of dual photon absorptiometry (DPA) was used to measure bone mineral density (BMD) in the crewmembers of the 6-9th expeditions onboard Mir orbital station after space missions of 132 to 176 days in duration. Total mineral losses were, on average, 0.4% of a preflight level, and in the most test subjects the postflight BMD of the skull, ribs and arms increased and that of lumbar vertebrae, pelvis and legs decreased. The most marked local postflight mineral losses occurred in the proximal femur bone (the femoral neck and the greater trochanter--up to 14%). The observed changes did not depend on flight duration. These findings are being compared to the results of similar studies conducted during the 120-day (NASA) and 370-day (IBMP) hypokinesia experiments. The possibility of existing the general mechanism of modifying mineral status of the skeleton due to different situation related deficiency of musculoskeletal load. PMID- 1307031 TI - [The giant multipolar neurons of the reticular formation in the rat brain stem after a 14-day space flight]. AB - The effect of a 2-week space mission on the geometry parameters of giant multipolar neurons of the brain stem reticular formation in the rats flown on board Cosmos-1887 and -2044 are studied. Compensation for a deficiency of vestibular informations from the trigeminal nerve system at the cost of an decreased length of the dendrites oriented toward primary sensory nucleus and from the vestibular system through an increase in the length of the vestibular sensory nuclei-oriented dendrites is discussed. PMID- 1307032 TI - [An experiment with Chlamydomonas reinhardtii on the Kosmos-2044 biosatellite]. AB - Space experiment with Chlamydomonas reinhardtii demonstrated that the microgravity effects were noted in Chlamydomonas at both cellular and population levels: in space the cell size is increased, stage of active growth of the culture is extended, it contains the juvenile vegetative motile cells in greater quantities. Ultrastructural analysis indicated that in microgravity the changes in shape, structure and distribution of intracellular organelles and in volume ratio of organelles and cytoplasma are absent. Chlamydomonas data are in line with the results of the Infusoria and Chlorella experiments. PMID- 1307033 TI - [The morphofunctional parallels in rat ovaries after 40-day hypokinesia]. AB - An effect of a 40-day hypokinesia produced by the stay of the white mongrel female rats in the small cages on their reproductive system was studied. The data being indicative of the involvement changes in the ovaries which appear as the decreased mass of an organ and qualitative alterations of its structures (depletion of germinate stroma, decrease in volumetric part of the follicles) have been obtained with the use of radioimmunologic technique, light-optical methods and quantitative analysis of tissue specimens. In this case, the yellow bodies become dominant structures in the ovary. A comparison of structural changes with progesterone and estradiol concentrations revealed a pronounced hormonal insufficiency of the follicles and yellow bodies. PMID- 1307035 TI - [The characteristics of the reparative process in the muscles when deprived of their functional loads]. AB - The time course of repair process in the tonic soleus and phasic gastrocnemius muscles of the head-down tail-suspended rats being traumatized directly prior to suspension or immediately after it. During first, suspension, the animals have been studied on the 17th suspension day and in the second 14-day suspension they were tested on the 14th and 17th post-traumatic days. It was indicated that the suspension results in muscle atrophy with a severely affected m. gastrocnemius loosing more than 40% of its mass. Under the effect of atrophy-induced factors in both muscles there equally occurred an inhibition of both the formation of connective stroma of repair field and the isolation of myoblasts from dedifferentiated muscular fibers due to which an extremely small-size repair field with the irregularly oriented muscular fibers and myoblasts has been originated. PMID- 1307034 TI - [The energy metabolism of the liver under the action on the body of different durations of hypokinesia]. AB - Studies of tissue respiration and oxidative phosphorylation of homogenates in the liver of white rats indicated that the 3-day hypokinesia is associated with a decreased rate of endogenic respiration and an increased amythal-resistant respiration. On the 10th day, there occurs a sharp increase of the oxidation rate of the endo- and exogenic substrates and the separation of oxidative phosphorylation takes place. During 30-day immobilization, the homogenate respiratory activity again decreases while on the 70-140th days of an exposure the oxidation rate of endo- and exogenic substrates increases with an increased effect of endogenic succinate on the hepatocyte energy metabolism. The possible mechanism disturbances in the liver of immobilized animals are discussed. PMID- 1307036 TI - [The effect of space flight on metabolism: the results of biochemical research in rat experiments on the Kosmos biosatellites]. AB - Cosmos biosatellites research program was the unique possibility to study the metabolic features influenced by space flight factors. Based on the existing ideas about relationships between some metabolic responses, the state of metabolism and the systems of its control in the rats flown in space was evaluated to differentiate the processes occurred in microgravity, possibly under effect of this factor and during first postflight hours. The biochemical results of studying the rats exposed to space environments during 7, 14, 18.5 and 19.5 days and sacrificed 4-11 h after landing (Cosmos-782, -936, -1129, -1667, -2044 flight) are used. The major portion of data are in line with understanding that after landing when the microgravity-adapted rats again return to 1-g environments they display an acute stress reaction. A postflight stress reaction is manifested itself in a specific way as compared to adequate and well studied model of acute and chronic stress and dictates subsequent metabolic changes. Postflight together with the acute stressful and progressing readaptation shifts the metabolic signs of previous adaptation to microgravity are shown up. In the absence of engineering feasibility to control or record the state of metabolism inflight it can only presupposed what metabolic status is typical of the animals in space environments and that its development is triggered by a decreased secretion of the biologically active growth hormone. This concept is confirmed by the postflight data. PMID- 1307037 TI - [Human biochemical status and its relation to body resistance to exposure to acute hypoxic hypoxia]. AB - Fourteen airworthy men, aged 19-20 yrs., participated in the experiments aimed at studying a prognostic significance of biochemical and hormonal parameters in evaluation of human tolerance to acute hypoxic hypoxia. Altitude chamber experiments were performed to study the tolerance to hypoxia by "ascending" the test subjects to an altitude of 6 to 7 km. It is found that under extreme hypoxic environments, of particular significance is an individual strategy of the adaptive responses and primarily an activity and adequacy of mobilization processes of energy resources in the preliminary and initial stages of an exposure. Of great value are the potential causes for maintaining the vascular tone. The use of a proposed discriminant function analysis for evaluating and predicting the tolerance to hypoxia is recommended. PMID- 1307038 TI - [Experimental high-altitude pulmonary hypertension in rabbits]. AB - In lowland (760 m above sea level) and highland (3200 m above sea level) of Tien Shan, the measurements of blood pressure and blood flow in the large vessels as well as the mass of heart ventricles of 75 rabbits have been made. In highland, the significant changes in hemodynamics of pulmonary circulation, appeared as elevations of pulmonary arterial pressure, pressure of wedging pulmonary artery, total and arterial pulmonary vascular resistance, have been noted. Besides this, adaptation to a highland staying was associated with an increased mass of the right ventricle of the heart. The pulmonary hypertension and hypertrophy of the right ventricle incremented during the first 2 weeks of the rabbits staying in highland and stabilized at achieved high level within succeeding 1.5 months of a tested period of adaptation. Because cardiac output and cardiac index starting from the end of 2nd week of adaptation did not differ significantly from control values, it can be said with confidence that an increase of pulmonary pressure in highland is dependent on a rise of pulmonary vascular resistance. In this case, the arterial pulmonary vascular resistance elevated to a greater extent than venous one. In highland, there revealed only the mean value of correlation relationship between the level of pulmonary blood pressure and a severity of right ventricle hypertrophy. The mass of left ventricle, systemic arterial pressure and total peripheral resistance did not significantly altered in a highland environment. PMID- 1307039 TI - [A mathematical model of the critical body tissue supersaturation during decompression]. AB - The paper deals with a permissible level of gas supersaturation (SS) of the body fluids and tissues used on the calculations of the decompression profiles on the basis of the features of a group set of superficially active substances skin stabilized gas nuclei containing in the fluids. Based on the biophysical laws, there developed a criterion and relation of critical SS of the body fluids and tissues which is a specific case of an allowable SS for prolonged decompression and for that one following excursion and repeat dives. The comparison of a computed cubic relation of critical SS has of ambient pressures with linear and quadratic dependences as well as with continuous SS revealed greater adequacy of the cubic relation over a wide range of pressures. PMID- 1307040 TI - [The effect of alcohol (ethanol) on the reactions of the vestibular system]. AB - The influence of ethanol upon dynamics of rotatory (RN) and post-rotatory nystagmus (PRN), trunk pose-tonic reflexes and their vegetative (cardiac, respiratory) components was studied in chronic experiments on rabbits with the help of electronystagmo- and electromyography. Ethanol was administered once intra-abdominally (1 g/kg) and one time a day during 30 days. Alcohol concentration in blood was determined by gas-and-fluid chromatography. The animal which were given isotonic solution of sodium chloride in the same doses and quantities served as a control group. It was established that vestibular oculomotor reflexes are mainly facilitated in an acute period of ethanol administration, then their inhibition occurs. Besides, the changes of PRN are stronger expressed than those of RN. Labyrinth pose-tonic reflexes are more often inhibited under the influence of ethanol; their strongest depression was observed during the first hour after ethanol administration and on the 15th day of chronic alcoholization. In alcoholization the changes of vestibular-vegetative reaction occur; primary short-term weakening of vestibular influences upon cardiac rhythm and respiration with their subsequent increasing. PMID- 1307041 TI - [The dynamic indices of human thermal status during overheating exposures]. AB - The thermal state of 7 naked test subjects on a 25 min of work (325 J/s) at 40 degrees C and 85% humidity of the ambient air has exceeded the acceptable limits. The thermal protecting garment having high thermal resistance indices was tested near a fire source. The subjects performed the 254 J/s and 403 J/s work so long as they were able to do it. Time of work was, on average, 17 and 12 min, respectively. By the end of work, thermal state of the subjects approached to a "limiting" value: heart rate and rectal temperature were, on average, 160-170 beats/min, and 38.3 degrees C, respectively. Three patterns of dynamics of core temperature of the body measured immediately after terminating the work have been observed. In the most experiments during first 5 min after leaving a fire zone there occurred a further temperature rise (by 0.2-0.5 degrees C). The conditions and levels of physiological indices at which there was a postwork incremental hyperthermia which is of prognostic significance have been determined. Among reasons of this phenomenon there can be a delay of thermal production from an increased oxygen consumption under conditions of ergothermal load, a reduced circulation and a surface-to-core heat transfer. PMID- 1307042 TI - [The reversibility of the action of solar UV radiation on the growth of and on the level of growth regulators in barley plants]. AB - Effects of UV radiation on a growth regulators activity of barley plants were studied in the West Pamir at 2.320 m above sea level. Inhibition of plant growth in a highlands environment was discussed. Inhibition appears as either a change of stimulating for inhibitory activity or an increased activity of the growth inhibitors. The plant growth inhibition during a bush phase which is a more sensitive period of growth in barley plants is reversible. PMID- 1307043 TI - [The permeability of rat erythrocyte membranes for sodium and potassium ions during exposure to pulsed electromagnetic field under head-down-tilt hypokinesia]. AB - The effect of a low-frequency (1 and 10 Hz) pulse electromagnetic field (PEMF) on permeability of erythrocyte membrane in 47 rats while being exposed to a 14-day head-down tilt (HDT) and in 60 control rats was studied. After exposure to PEMF (20 min, 6-24 mT) the rats were Na(+)-, K(+)-cotransport and Na+,Na(+) metabolism, Na and K losses as well as specific activity of Na(+)-, K(+)-ATP in the erythrocytes have been measured. An ability of PEMF to inhibit an ATP activity by 20-30% and to increase the rate of ions loss from the cells has been revealed. Under HDT, these effects are preserved. The possible mechanisms of PEMF effect on an ionic permeability of the membranes are discussed. PMID- 1307045 TI - [The experience of using therapeutic and diagnostic manipulations under ultrasonic control for the purposes of medical flight expertise]. AB - The paper deals with an experience in application of diagnostics and treatment of 28 pilots with the use of medical manipulations under ultrasound control. The procedure of the abdominal cavity and retroperitoneal space organs is covered in detail; an effectiveness of such type of surgery is shown. A wide use of these invasive methods of diagnostics and treatment for the purpose of aeromedical certification is recommended. PMID- 1307044 TI - [The treatment and prevention of ischemic heart disease in stress states by using laser radiation and transcutaneous electric nerve stimulation]. AB - An effectiveness of treatment and prevention of ischemic heart disease (IHD) using laser rays and transcutaneous electroneurostimulation (TENS) in 144 patients who underwent myocardial infarction and in whose clinical characteristics of a disease there prevailed chronic painful syndrome, was studied. An analgesic effect of TENS was achieved by an application of TENS to cardiac area and Zakharin-Head's zones. Low-intensity laser rays were applied for both irradiating projections of the heart and the large vessels and irradiating the biologically active points using unique procedure. All patients had a positive clinical effect resulted from applying laser and TENS which appeared as a decreased number of stenocardia attacks, an increased tolerance to exercise and as positive ECG dynamics. Duration of remission in the main group of patients exceeded the remission length in the control group in 2.7 times which is indicative of the effectiveness of using laser therapy and TENS as a tool of urgent medical aid under stresses induced by the development of life-threatening states. Small-size laser and TENS apparatuses are proposed for use as an onboard medical equipment. PMID- 1307046 TI - [The assessment of the public health status of flight personnel]. AB - A set of the objective quantitative parameters characterizing a pilot health status in a generalized form is required to manage the medical examination system. The medical and statistical data are proposed to be used. The major indices of health status of a group of pilots (public health) are: 1. Probability estimation of threat to space mission safety due to a sudden incapacitation of a pilot; 2. Evaluation of medical disqualification rate per mile of pilots tested; 3. Flying longevity of the pilots evaluated as an average duration of forthcoming flying activity; 4. Prevalence of diseases and factors of their risk determined from the standardized criteria. The methods of obtaining the mentioned and some other quantitative data on pilot personnel of the former Soviet Civil Aviation are discussed. It is indicated that at present the level of health threat to flight safety conforms to the general safety standards. PMID- 1307047 TI - [The ecological-physiological and age-related characteristics of the flight activities of pilots in Colombia]. PMID- 1307048 TI - [Tracking eye movements in aquanauts breathing trimix at 26-ata pressure]. PMID- 1307049 TI - [The chemical sensitivity of neurons in the medial vestibular nucleus to regulator peptides]. PMID- 1307050 TI - [The effect of a preparation isolated from reindeer spleen on the survivability of mice at low temperatures]. PMID- 1307051 TI - [The effect of short-term adaptation to high-altitude conditions on human blood serum lipoproteins]. PMID- 1307052 TI - [Evaluation of three plants with potential diuretic effect]. AB - To evaluate three natural products with potential diuretic effect, Elephantopus scaber, Alpina speciosa and Tradescantia diuretica it was performed a trial of acute administration in 10 healthy volunteers, with interval of 7 days for each dose, except Tradescantia diuretica which was administered with 60 days of interval. All groups were compared with placebo group. The three products were given doses 5 times higher than the usually preconized by the popular use, i.e., 7.5 g/100mL, 0.8g/100mL and 25g/100mL of water, respectively. Besides physical examination, plasmatic and urinary parameters of sodium, potassium, uric, acid, calcium, phosphate, urea, creatinine and total urinary volume were evaluated. The only significant data were a light increase in diuresis (p < 0.05) with Alpinia speciosa, which also lowered the mean diastolic (p < 0.05) and systolic (p < 0.01) blood pressure. We did not found any effect in electrolytes excluding therefore, a tubular effect of these teas in modifying Na, K, Ca, P and uric acid excretions, as well as any detectable glomerular action since no changes were observed in renal function parameters. PMID- 1307053 TI - [Use of substances for immediate management of pain in patients with headache. Study in an ambulatory population]. AB - Data about the use of pain relieving drugs in 411 patients, collected during 24 months are presented. The patients were interviewed personally by one of the authors during a selection process. Demographic data were obtained as well as information about headaches and other pains, duration of the disease, previous headache treatment, clinical characteristics of the headache and a diagnostic hypothesis was formulated. Regarding the use of medication the following factors were considered: amount and quality of medication taken, duration of disease, person responsible for the prescription and awareness of side effects. The results showed that 82% of the patients used substances for immediate relief to headache. Eighty per cent of these patients used commercial products without ergot derivatives, 9% with ergot derivatives and 12%, both. At the same time, 27% of the patients used 3 or more commercial products. The most frequently used substance was dipyrone. Several patients used, as PRD, substances without these properties. Forty eight per cent of the patients used PRD daily or more than once a day and 63% used them for over 90 days. Thirty two per cent of the patients used 5 or more doses of PRD during one single crisis of pain. Seventy four per cent of the patients used self-medication and 81% were not aware of side effects. The present data indicate that the use of PRD is high and chronic. The main implications of this fact and preventive measures are discussed. PMID- 1307054 TI - [Organ donation for transplant: a human response to death]. AB - Dialysis instead of kidney transplantation remains the available treatment for most of the uremic Brazilian population. The low percentage of transplants of cadaver donors (20%) that occurs in Brazil is insufficient to prevent the progressive accumulation in the number of individuals requiring transplants. Our investigation shows that 86.6% of the people of Londrina know the importance of organ donation but actually only 36.4% would sign a donor card. Most of them mentioned not being fully acquainted with the matter, a fact to suggest we should increase our efforts at extending to the population further knowledge on death and dying. PMID- 1307055 TI - [Abuse of substances for immediate management of pain in patients with headache]. AB - Data on the use of pain relieving drugs in 339 patients who used medication to relieve their headache are presented. One hundred sixty eight (49%) of them were considered as abusers based on Diamond and Dalessio's criteria modified by Saper. The most common form of abuse was the daily use of PRD, observed in 90 (54%) of the patients (criterion A) followed by: abuse by criterion A plus use of more than 100 doses of analgesic/month (criterion B) observed in 18 (11%) and finally criterion A plus daily use of compounds containing barbiturates or other tranquilizing drugs, in 18 (11%) of the patients. The abuse by psychotropic drugs was observed in 11 (7%) of the patients. The data suggest that the abuse of PRD is high and must be regarded as a public health problem. PMID- 1307056 TI - [Diabetic ketoacidosis in a Krenak Indian]. AB - The authors present a case of spontaneous ketoacidosis developed by one 32 years Krenak indian. The patient denied alcoholism and his mother had Type II diabetes for the last 3 years. The search to islets and insulin autoantibodies was negative in this patient. The basal C-peptide was found normal during follow-up. The patient received a short insulin therapy and now he shows good metabolic control (normal glycosylated hemoglobin) with oral hypoglycemic treatment. The environment influence, indian customs and the rarity of spontaneous ketoacidosis in these individuals were reviewed and discussed. PMID- 1307057 TI - [Hepatic hydatidosis with glomerular involvement: report of a case]. AB - A patient with hydatid cyst of the presented stunted growth, normal renal function and no significant proteinuria. The radiological abdominal investigation disclosed, besides the hydatid cyst, horseshoe kidneys. Renal biopsy was performed during surgery. Immunofluorescence (direct and indirect) and immunoperoxidase studies revealed glomerular deposits of hydatid antigen and its corresponding antibody. A grade I immune complex type of membranous glomerulonephritis, without significant clinical signs, was diagnosed in association with the hepatic hydatid disease. PMID- 1307058 TI - [Cushing's disease: diagnostic, therapeutic, and prognostic evaluation]. PMID- 1307059 TI - [Evaluation of the immunological response to hepatitis B vaccine in health care professionals]. AB - Clinical trials have shown the safety and efficacy of Hepatitis B (HB) vaccination, but it is well known that host and immunization factors can affect the response to HB vaccine. In order to assess the importance of some of these factors we evaluated the immune response of 86 health care workers who received three doses of H-B-Vax intramuscularly (deltoid), at days 0, 30 and 180. Serum samples were taken after each dose and anti-HBs antibodies were determined by quantitative radioimmunoassay. The results showed that males had a diminished immune response to the first dose of HB vaccine (31.7% x 53.3%, p < 0.05) and had geometric mean titers (GMT) of anti-HBs lower than females at the end of the vaccination program (2109.4 x 2453.8, p > 0.05). Smokers had a lower rate of seroconversion after the first dose (29.7% x 53.1%, p < 0.05) and reached lower GMT (2015.2 x 2453.8, p > 0.05) than non-smokers. There were no statistically significant differences between individuals younger or older than 35 years old, in either immunological response of level of anti-HBs. PMID- 1307060 TI - [Are there liver protective drugs really?]. PMID- 1307061 TI - [Toxic nodular goiter associated with follicular carcinoma in a Xavante Indian]. PMID- 1307062 TI - [Incidence of symptomatic megacolon in patients with chagasic megaesophagus]. AB - The authors analyze the incidence of megacolon associated to megaesophagus during a 7 year period. Of the 192 patients with megaesophagus only 15 who presented associated intestinal symptoms were further investigated through barium enema. No statistically significant differences were found between the group with megaesophagus and the group presenting association of megaesophagus and megacolon as to sex and age of the individuals and severity of megaesophagus. The esophageal symptoms preceded the intestinal symptoms in 93.3% of the cases. Many treatments were used, but recently good results were obtained by the association of Heller's cardiomyotomy with modified Lortat-Jacob's technique and left hemicolectomy. PMID- 1307063 TI - [ABO incompatibility in organ transplant. Report of case and review of the literature]. AB - One case of a multiple organs donor that resulted in kidney and heart transplants with inadvertent ABO incompatibility is described. The renal recipients showed the presence of high anti A antibodies titers. The reviewed publications have revealed that the preparation of the receptor with plasmapheresis and splenectomy, before the transplantation may prevent the hyperacute rejection on ABO incompatible organs allografts. In emergency situations, liver transplantation is accepted with ABO incompatible donor without previous treatment. PMID- 1307064 TI - [Ogilvie's syndrome]. PMID- 1307065 TI - [Mechanisms of action of immunosuppressive drugs in organ transplantation]. PMID- 1307066 TI - [Recombinant human erythropoietin]. PMID- 1307068 TI - [Epidemiology of bacteremias at a university hospital]. AB - The epidemiological aspects of bacteremias were determined in a university hospital, according to service, age, sex and place of acquisition (nosocomial or community-acquired). From August 1985 through July 1986 the incidence rate of bacteremias at the Sao Paulo Hospital was 21.7/1000 admissions. Such a high rate is probably related to the characteristics of the patients admitted to the hospital. The incidence was higher in the extremes of age and was similar in either sex. Approximately 60% of the bacteremias were nosocomial including 9.1% that were present at admission in patients transferred from other hospitals. The most frequent isolated pathogen was S. aureus. The most important source of bacteremia was the respiratory tract followed by the gastrointestinal and urinary tracts. PMID- 1307067 TI - [Use of recombinant human erythropoietin in the treatment of anemia in hemodialyzed patients: a multicentric study]. AB - Recombinant human erythropoietin (rHu-EPO) therapy was given to 25 patients undergoing long-term hemodialysis, for 12 weeks, in 5 Brazilian dialysis centers. The dose of rHu-EPO was given intravenously thrice weekly, initially at 50 Units/kg/dose. If the target hemoglobin concentration (10g/dL) was not achieved by four weeks the dose was increased to 75 and 100 Units/kg/dose. After 4 weeks hemoglobin concentration had achieved 10g/dL in only one patient, and, after 8 weeks, 10 patients (40% of all cases) had hemoglobin levels higher than the target concentration. After 12 weeks, the hemoglobin increased from 7.1 +/- 1.1 to 9.6 +/- 1.2 g/dL, the target hemoglobin concentration was achieved in 15 patients (60% of all cases). There was a significant (p < 0.05) increase in hematocrit (from 22 +/- 4 to 31 +/- 4 vol%), in body weight (from 55.03 +/- 12.24 to 56.16 +/- 12.86kg), and in serum phosphorus (from 5.85 +/- 2.02 to 6.82 +/- 2.34 mg/dL). There were no significant changes in blood pressure, serum levels of creatinine, of potassium, and of transferrin. Increase in blood pressure (in 3 patients), fever (in 2 patients), increase in the heparin dose needs (in 2 cases), and vascular access thrombosis (in 1 patient) were the most important adverse effects observed during rHu-EPO therapy. Thus, the anemia of chronic renal failure may be easily corrected with adequate amounts of recombinant human erythropoietin. Attention must be paid to some adverse effects during reversal of anemia. PMID- 1307069 TI - [Beclomethasone dipropionate, in high dose, in the treatment of patients with chronic persistent asthma]. AB - The efficacy of inhaled beclomethasone dipropionate (BDP) was examined in 8 patients with chronic persistent asthma, uncontrolled by inhaled bronchodilators and oral theophylline. Beclomethasone was administered at a dose of 1500 mcg a day, using a metered dose inhaler containing 250 mcg of BDP per dose. The medication was administered twice daily, three 250 mcg puffs at 8 A.M. and three at 8 P.M. The patients were assessed by means of clinical examination, diary records and daily Peak Flow Rate (PFR) measurement made at home. The therapeutic responses were measured over an 8-wk period. The clinical score (0-4) improved significantly (3.25 +/- 0.71 before and 0.75 +/- 0.89 after [p < 0.001]), and the peak flow rate rose from baseline mean value of 48.0% +/- 11.9 (predicted value) to 78.8% +/- 16.7% with significant improvement (p < 0.01). Of the total of 8 patients, 5 achieved complete control of symptoms and normal values of PFR, 1 remained with sporadic wheezing but with significant improvement of PFR and 2, despite the clinical efficacy in symptom relief, persisted without significant improvement on PFR values. Transitory hoarseness occurred in 1 patient. No other side-effects were observed. PMID- 1307070 TI - [Medical records--ethical aspects]. PMID- 1307071 TI - [The patients' perception about their illness: a pilot study]. AB - This preliminary study aims at inquiring the patients' perceptions about their own illness process. Therefore, 19 clinical inpatients from the Hospital de Clinicas de Porto Alegre interviewed. After a qualitative data analysis, it was observed that in a medical consultation there are, at least, two perspectives concerning the illness process. First, the physician's perspective, taking into account systems and organs structural and/or functional abnormalities (disease), and second, the patient's perspective, based on her or his perception of events that occur when getting sick (illness). In addition, the patient's perspective generally presents a preoccupation with the etiology of the disease. Keeping in mind these different viewpoints, it is crucial to establish the medical-patient dialog, aiming at reaching a better relationship between the patient and her/his physician. PMID- 1307072 TI - [Nontoxic multinodular goiter: evaluation of recurrence rate and function after partial thyroidectomy. Retrospective analysis of 39 cases]. AB - The postoperative goiter recurrence and hypophysial-thyroid function in 39 patients who underwent partial thyroidectomy for nontoxic multinodular goiter, during the 1970-1983 period, was evaluated, seeking relations among thyroid function, extension of surgery and goiter recurrence. The incidence of recurrent goiter was approximately 15%, most of these goiters having been identified ten or more years after thyroidectomy. More extensive surgery lowered the recurrence rate but increased the risk of subclinical-hypothyroidism. No statistical significant differences with regard to serum T3, T4, F T4 and TSH (basal and after TRH) of patients with and without recurrent goiter were found. Thus, the maintenance of a recurrent nontoxic goiter does not seem to depend exclusively on increased serum TSH levels. In one patient, the postoperative treatment with thyroxine did not prevent the appearance of recurrent goiter. Since most patients who underwent thyroidectomy remain euthyroid and the goiter recurs in only a small number, the routine postoperative use of thyroid hormone for the prophylaxis of multinodular goiter recurrence seems to be questionable. PMID- 1307073 TI - [Rheumatic manifestations of acquired immunodeficiency syndrome (AIDS)]. AB - 120 AIDS patients (mean age 33 +/- 9 years, 108 males) were evaluated regarding rheumatic manifestations. According to CDC's classification, 18.3% belonged to group II, 28.3% to group III, and 53.4% to group IV. Arthralgia was present in 33 patients (27.5%), and in only 8 could be associated with infections other than HIV (5 cases of tuberculosis, 3 P. carinii, and 1 gonococcal infection). Incidence of arthralgia was equal in either sex. Arthritis was present in 8 patients, 2 of them with Reiter's syndrome. In 6 patients arthralgia was the first symptom (3 with arthritis) before AIDS diagnosis. There was a higher incidence of dry mouth, dry eyes, and muscular complaints in patients with arthralgia than in patients without arthralgia. Antinuclear antibodies and rheumatoid factor were absent in the serum of the patients studied. Arthritic manifestations possibly occur in AIDS, even in patients without other clinical manifestations, as a reactive state to HIV infection. PMID- 1307074 TI - [Medical audit in surgery]. AB - Recording clinic data is essential to the process of evaluation of medical proceedings but, unfortunately, it is not a common practice among us. Therefore practitioners are not able to recall all their own medical records. We must know the therapeutic results to improve preceding decisions. Is has been hard to characterize the quality of medical care because of the lack of clinic data. Medical auditorship applies itself to define philosophical questions and to determine useful values in professional and scientific fields, available to any surgeon. Establishing an auditorship is first a need, second a choice. The evaluation of successful therapy and the rates of morbidity and mortality is the minimum we can expect in the immediate future. PMID- 1307076 TI - Dispersal in sub-Saharan baboons. AB - In most mammalian species, males tend to leave their natal group and disperse farther than females, while females tend to be philopatric. Primates generally follow this rule, although long-term studies of a variety of species are revealing an increasing number of exceptions. This paper reviews dispersal patterns in 3 subspecies of savanna baboons (Papio cynocephalus cynocephalus, P. cynocephalus anubis, P. cynocephalus ursinus) which exhibit very similar patterns of social organization. Males usually disperse from the natal group at 8-10 years of age. Female dispersal is rare but well documented. Inbreeding avoidance as well as enhanced mating opportunities are suggested as ultimate causes of dispersal. Several proximate factors implicated in the timing of dispersal events are also reviewed. PMID- 1307075 TI - [Estimation of the number of potential organ donors in the city of Sao Paulo]. AB - BACKGROUND: There is a concept that the small number of transplants is due to the shortage of donors or the refusal of the next of kin to make to donation. In order to evaluate the potential number of donors in Sao Paulo the autopsies performed at the Forensic Medical Institute (IML) were studied during 1990 and 1991. MATERIAL AND METHOD: The autopsies carried out during 1990 and 1991 were studied. During the same period we also analysed the reports of possible donors received by the organ searching team of the Escola Paulista de Medicina (EPM). RESULTS: During 1990 and 1991, 11601 and 11607 autopsies were respectively carried out (32 autopsies/day). The analysis of 500 autopsies during 10/90 and of 1039 during 05/91 showed that 27% had a traumatic brain injury (TBI) as the sole cause of death and 70% were cared for in a hospital. From 01/90 to 12/91 the organ searching team of the EPM received reports of 296 possible donors. Of the 296 reports, 219 families were contacted and 59% authorized the donation. CONCLUSION: Considering the number of deaths exclusively caused by TBI that passed through any hospital and the rate of donations obtained by our team, there is a number of potential donors in Sao Paulo sufficient to saturate the working capacity of all teams, if the seeking system is efficient. PMID- 1307077 TI - Effects of periodic removal and reintroduction on the social and sexual behavior of stumptail macaques (Macaca arctoides). PMID- 1307078 TI - Aging and social behaviour in captivity in Microcebus murinus. PMID- 1307079 TI - Comparison of dental dimensions between Rhinopithecus bieti and Rhinopithecus roxellanae. PMID- 1307080 TI - Study of the seminiferous epithelium cycle in Eulemur hybrids. PMID- 1307081 TI - The use of respiration as a physiological variable in rate adaptive cardiac pacing. PMID- 1307083 TI - Influence of low dose enteric-coated aspirin on platelet function. AB - Little is known about the effect of low dose, enteric-coated aspirin on human blood platelet function. This study was conducted to evaluate the acute effects of a single daily dose of commercially available enteric-coated aspirin on platelet biochemistry, physiology and function. Blood for these studies was obtained from drug-free volunteer donors prior to ingestion of aspirin or following ingestion, either before breakfast or following lunch. Response of platelets to the action of weak agonists was evaluated. In addition, ability of platelets to convert radiolabeled arachidonic acid to thromboxane was monitored. Results of our studies show that a single daily dose of 50 mg of aspirin taken either before breakfast or after lunch effectively prevented the secondary wave aggregation response, as well as secretion of dense body contents when stimulated by agonists such as epinephrine and ADP. Aspirin ingestion caused a dose dependent inhibition of platelet cyclooxygenase activity as evidenced by the extent of arachidonic acid converted to thromboxane by platelets exposed to aspirin for different time periods. Based on these observations, it is suggested that low dose aspirin may be very useful and desirable to restrain platelet activity in clinical situations in which increased thromboxane formation may initiate vascular hypertension and platelet hyperactivity. PMID- 1307082 TI - Catheter ablation of retrograde fast pathway in patients with atrioventricular nodal reentrant supraventricular tachycardia. AB - Atrioventricular (AV) nodal reentrant tachycardia is a common cause of supraventricular tachycardia. The present study describes catheter ablation of this form of tachycardia in 23 patients using direct current shocks. The aim of ablation was to abolish conduction through the retrograde pathway while preserving the anterograde conduction. All patients had symptomatic, drug resistant, slow-fast variety of dual atrioventricular nodal reentrant tachycardia. Using the retrograde atrial activation in the His bundle catheter as the reference, the optimal ablation site was selected by positioning an electrode catheter to obtain atrial activation synchronous with or earlier than the atrial activation at the reference electrode. Shocks of 100-300 joules were delivered at this site resulting in blockade of retrograde conduction in all patients. Ventriculo-atrial conduction studied 24 hours after the procedure was still absent in 16, modified in 2 and resumed in 3 patients. Two patients developed permanent complete heart block and were given pacemakers. At repeat electrophysiologic study performed after 2-4 months in 10 patients, the supraventricular tachycardia could not be induced. The AH interval was 67 +/- 10 msec during control study and to 115 +/- 39 msec at restudy (p < 0.001). The ventriculo-atrial conduction was absent in 7 cases and had been modified in 1 case. Over a follow up period of 1-30 months (mean 10.8 +/- 7.1 mo) 17 patients (73%) remained free of the arrhythmia without medication or pacemaker. Three other patients were easily controlled with digoxin. Thus, catheter modification of AV node results in permanent cure of the AV nodal tachycardia in majority of patients. PMID- 1307084 TI - Low dose aspirin therapy in prophylaxis of cardiovascular disease--how low is low? PMID- 1307085 TI - X-syndrome: myocardial perfusion during stress testing. AB - Stress T1-201 myocardial scintigraphy was carried out in 16 patients with X syndrome. 11 patients with ischaemic heart disease (IHD) with single vessel disease served as controls. With bicycle exercise test all 16 pts with X-syndrome had various types of myocardial perfusion abnormalities. These perfusion defects were situated in the vascular beds of different coronary arteries. Myocardial perfusion defects in patients with X-syndrome were similar to those in patients with moderate, but haemodynamically significant, single vessel disease. At the same time, these perfusion defects were significantly less pronounced than those in patients with subtotal occlusion of one coronary artery. Thus, patients with X syndrome not only have clinical features of IHD (anginal attacks), but have marked stress-induced myocardial perfusion defects. PMID- 1307086 TI - Hemodynamic changes during dynamic exercise in patients after mitral valve replacement for chronic mitral regurgitation. AB - To evaluate hemodynamic changes during dynamic exercise, we investigated 13 patients after mitral valve replacement (MVR) for chronic mitral regurgitation (MR) and 5 control subjects by right heart catheterisation during supine bicycle exercise. According to the sizes of the St. Jude Medical (SJM) prosthesis during MVR, patients were divided into group A (n = 8) with SJM 31mm and group B (n = 5) with SJM 29mm. Significant rise in cardiac index (CI) was noted during exercise in both groups A and B (from 3.3 +/- 0.8 to 5.5 +/- 0.9 l/min/m2, p < 0.01 and from 3.0 +/- 0.6 to 5.6 +/- 0.6 l/min/m2, p < 0.01 respectively) and also in control subjects (from 3.4 +/- 0.7 to 6.2 +/- 0.6 l/min/m2, p < 0.01). Mean pulmonary artery and pulmonary capillary wedge pressure were significantly higher during exercise in patients of both groups A and B than control subjects (p < 0.05 and p < 0.01 respectively). Total pulmonary vascular resistance was significantly higher during exercise in both groups A and B than control subjects (p < 0.05 and p < 0.01 respectively). No difference in hemodynamics were noted between the patients of group A and B during exercise. It is concluded that response of CI to exercise in patients after MVR for chronic MR was adequate in comparison to control subjects irrespective of two different valve sizes. PMID- 1307087 TI - Cardiac amyloidosis: hemodynamic, echocardiographic and endomyocardial biopsy studies. AB - Six patients with cardiac amyloidosis (four males, two females; age 27-60 years) were evaluated by us. Four patients presented with congestive heart failure, while one patient each presented with effort angina and giddiness. Extracardiac clues to the diagnosis in the form of involvement of other systems were present in only two patients. The electrocardiogram was abnormal in four patients while three exhibited roentgenographic evidence of cardiomegaly or pulmonary venous hypertension. Echocardiography suggested the diagnosis of amyloidosis in only two patients, restrictive cardiomyopathy in two other patients and dilated and hypertrophic cardiomyopathy in one patient each. Cardiac catheterisation and angiography suggested restrictive heart disease in four patients and hypertrophic cardiomyopathy in one. One patient, whose initial haemodynamic study was normal, had features of dilated cardiomyopathy at repeat study after 11 months. Endomyocardial biopsies showed amyloid deposits in all patients. We emphasise the varied clinical manifestation of cardiac amyloidosis and the need for a high index of suspicion. The diagnosis can be safely and reliably confirmed by endomyocardial biopsy. PMID- 1307088 TI - Role of transesophageal echocardiography during balloon mitral valvuloplasty. AB - Transoesophageal echocardiography (TEE) was performed during balloon mitral valvuloplasty (BMV) in 40 patients of rheumatic mitral stenosis, to assess its feasibility and additional benefits. The age range was 12-35 (mean 20 +/- 6) years. Patients were in an unsedated state and the procedure was tolerated by all without any complication. High resolution images of the interatrial septum and the puncture assembly were obtained which guided the septal puncture. In eight (20%) patients, puncture assembly had to be readvanced into superior vena cava and withdrawn down to obtain a satisfactory position for puncture. In 2 additional cases, the puncture assembly was redirected towards the fossa ovalis region under TEE guidance alone to obtain a successful septal puncture. TEE was not found useful in either negotiating the mitral valve or positioning the balloon catheter across it. PMID- 1307089 TI - Diagnosis of the sinus venosus defect by echocardiography and angiocardiography. AB - A retrospective analysis of forty five cases of sinus venosus defect was done to compare the ability of transthoracic echocardiography, transesophageal echocardiography and cineangiography in diagnosing this lesion. Left atrial and superior vena cava angiography delineated sinus venosus defect accurately in all the 45 cases (100%). Transthoracic cross-sectional echocardiography combined with colour flow mapping could visualize this defect in 28 out of 45 cases (62.2%) and proved inferior to transesophgeal technique which diagnosed the defect in all the 8 cases (100%) studied. An anomalous venous connection associated with sinus venosus defect was best diagnosed at cardiac catheterization although transesophgeal technique seems promising. PMID- 1307090 TI - Intracardiac blood flow velocities and cardiac output in normal fetuses: a prospective pulsed Doppler echocardiographic study. AB - Two dimensional and pulsed Doppler echocardiographic studies were performed in human fetuses with the aim to establish normal values for blood flow velocities and cardiac output in Indian subjects. Thirteen pregnant mothers were prospectively followed up at 4 weeks interval from 19 to 40 weeks of gestation. Blood flow velocity spectra across aortic, pulmonary, mitral and tricuspid valves were analyzed to obtain peak flow velocity (cm/sec) and velocity time integral. Aortic and pulmonary diameters were measured at the valve level from two dimensional echocardiographic images and ventricular stroke volume calculated. The values were plotted against fetal age (weeks) and fetal weight (gms). Our results showed that there is a linear increase of the measured Doppler data, with increasing gestational age and weight. These values may be used as a reference for the Indian population. PMID- 1307092 TI - The Modified Porstmann's technique of transcatheter occlusion of patent ductus arteriosus. PMID- 1307091 TI - Continuous ambulatory electrocardiographic changes after rapid ascent to extreme altitude. PMID- 1307093 TI - Aortic-left ventricular tunnel--a case report. PMID- 1307094 TI - Demonstration of atrioventricular dissociation due to complete heart block by pulsed Doppler echocardiography of hepatic veins. PMID- 1307095 TI - Plasma adenosine and cardiovascular responses to dipyridamole in fetal sheep. AB - The effects of dipyridamole infusion on fetal arterial plasma adenosine level, [ADO], and the systemic cardiovascular system were studied in 10 fetal sheep at 130-135 days gestational age. Dipyridamole (0.25 mg/kg) was infused into the fetuses intravenously during normoxia and hypoxia. Plasma [ADO] was measured using high-performance liquid chromatography, (HPLC), and fetal heart rate and arterial blood pressure were monitored throughout the study. These studies were performed in the absence and presence of theophylline, an adenosine receptor antagonist. During normoxia (PO2, 23.8 +/- 2.0 Torr), dipyridamole infusion increased fetal plasma [ADO] from 0.82 +/- 0.10 microM to 1.41 +/- 0.16 microM within 1 min (P < 0.01) and fetal heart rate from 157 +/- 6 bpm to 174 +/- 7 bpm (P < 0.01), but did not change mean blood pressure. Fetal plasma [ADO] and fetal heart rate returned to basal levels quickly. Treatment with theophylline did not alter the elevation of plasma [ADO] after dipyridamole infusion, but abolished responses of fetal heart rate to dipyridamole infusion. After 15 min of hypoxia with an average arterial PO2 of 15.4 +/- 1.1 Torr, fetal plasma [ADO] increased to 1.15 +/- 0.14 microM (P < 0.01). Dipyridamole infusion then further raised fetal plasma [ADO] to 1.67 +/- 0.27 microM (P < 0.01). The duration of the increase of fetal plasma [ADO] after dipyridamole infusion was no longer in hypoxia than in normoxia, however there was no significant change in the pattern of transient fetal bradycardia and persistent hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307096 TI - Developmental changes in plasma erythroid colony-stimulating activity in mice: cyclic erythropoiesis associated with rapid growth. AB - To establish a role of erythropoietin (Epo) in regulation of fetal and neonatal erythropoiesis, plasma erythroid colony-stimulating activity (ECSA) in developing mice was measured by an erythroid colony-forming assay using fetal mouse liver cells. The ECSA in fetal and neonatal plasmas showed dose-response curves parallel to standard Epo curve and additive effects with standard Epo on the colony formation. Most of the plasma ECSA was neutralized by an anti-Epo monoclonal antibody. These results suggest that the plasma ECSA detected by the present bioassay is predominantly due to Epo. On day 12-14 of gestation, the plasma ECSA levels were at the highest values; thereafter the levels oscillated up to the age of 4 weeks. The packed cell volume (PCV) also oscillated, but with the reverse phase. Oscillation in PCV was associated with the growth. There was an inverse relationship between plasma ECSA and PCV levels throughout the prenatal and early postnatal periods. The results indicate that erythropoiesis in fetal and neonatal mice is regulated mainly on the basis of PCV-ECSA feedback control mechanism. PMID- 1307097 TI - Selected physiologic measures and behavior during paternal skin contact with Colombian preterm infants. AB - A descriptive study of eleven healthy preterm infants was conducted in which cardiorespiratory (heart and respiratory rates, oxygen saturation), thermal (abdominal, toe and tympanic temperatures) and state behavior responses to two hours of paternal skin-to-skin contact within the first 17 hours of birth in Colombia, South America were evaluated. Infant physiologic and behavioral state measures were recorded each minute as was paternal skin temperature and behavior. Infant heart and respiratory rates increased during paternal contact as did abdominal and core temperatures. Fathers were able to keep their infants sufficiently warm, and five infants became hyperthermic (tympanic temperature greater than 37.5 degrees C) despite cooling measures while being held in this climate. Infants slept most of the time while being held and fathers seldom gazed at, spoke to, or touched their infants while holding them. When mothers are unavailable, fathers may be an alternate source of warmth and comfort to infants. PMID- 1307098 TI - Collagen and elastin in rabbit fetal lung: ontogeny and effects of steroids. AB - Ontogeny of lung collagen and elastin were studied in fetal rabbit from day 25 to term. Collagen (isolated by hot trichloroacetic acid treatment) and elastin (contained in the residue) were hydrolyzed and the hydroxyproline and desmosine quantitated by hplc. Hydroxyproline slightly increased from day 25 to day 30 (204 to 244 micrograms/100g dry weight). Over the same period desmosine increased from 2.2 to 5.1 micrograms/100 mg dry weight (P < 0.01). The effect of antenatal corticosteroids on the lung of prematurely-delivered fetuses was also evaluated. Betamethasone (B) was given to pregnant does at a dose of 0.2 mg/kg 24 and 48 h before delivery of the fetuses at 26, 27 and 28 days. In treated animals elastin concentration increased significantly by about 22% on day 26 (P = 0.05), by 29% on day (P < 0.02) and by 47% on day 28 (P < 0.02). Hydroxyproline was not affected by steroid treatment at any gestational age. This suggests that steroids affect fetal lung development also via changes in connective tissue. PMID- 1307099 TI - The effects of 21 or 30% O2 plus umbilical cord occlusion on fetal breathing and behavior. AB - We have shown previously that continuous fetal breathing can be induced by 100% O2 alone or combined with umbilical cord occlusion (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). To know whether it could also be induced by lower O2 concentrations plus cord occlusion, we studied 9 chronically instrumented fetal sheep (16 experiments) using our window model. After a baseline cycle [1 low voltage + 1 high voltage electrocortical activity (ECoG) epoch] the fetal lung was distended via an endotracheal tube to about 30 cm H2O. Inspired N2 (control) and 21 or 30% O2 were given for one cycle each. While on 21% or 30% O2 the umbilical cord was occluded (balloon cuff). In 10 out of 16 experiments breathing output (% maximum of integral of EMGdi x f) increased after cord occlusion from 80 +/- 48 (N2) to 2871 +/- 641 (SEM; P < 0.01); in 7 of them breathing became continuous. Arterial PO2 increased from 14 +/- 1 (N2) to 33.5 +/- 5 Torr (occlusion; P < 0.01). In the other 6 experiments breathing output decreased from 319 +/- 116 (N2) to 86 +/- 38 (occlusion; P < 0.01) and arterial PO2 changed from 18 +/- 1 (N2) to 22 +/- 5 Torr (occlusion; P = 0.4). Arterial PCO2 increased similarly after occlusion in both groups, those which did respond with increased breathing (to 46 +/- 2 Torr) and those which did not respond (to 48 +/- 3 Torr; P = 0.6). The percent low voltage ECoG and the behavioral score increased after occlusion in the responder group only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307100 TI - Ontogeny of glutamate and gamma-aminobutyric acid release in the hippocampus of the guinea pig. AB - The ontogeny of the L-glutamate (GLU) and gamma-aminobutyric acid (GABA) neuronal systems in the guinea pig hippocampus was investigated with respect to tissue amino acid content, and spontaneous and K(+)-stimulated release of GLU and GABA. Transverse hippocampal slices were prepared from the guinea pig fetus at day 45 (brain growth spurt), 55 and 63 of gestation (term, about 68 days), from the 5 days-old neonate, and from the young adult. GLU and GABA release was determined as efflux from hippocampal slices into Krebs'-bicarbonate medium using a dynamic, submerged, superfusion apparatus. Hippocampal GLU content decreased during development, whereas GABA content was constant for all the ages investigated. The magnitude of spontaneous GLU efflux decreased during development; there was no measurable spontaneous GABA efflux. The K+ concentration-GLU efflux response curve was bell-shaped for the fetus at the three selected gestational ages, and was curvilinear for the neonate and adult. The apparent EC75 of K(+)-stimulated GLU efflux was higher for the neonate and adult compared with the fetus. In contrast, the K+ concentration-GABA efflux response curve was curvilinear, and the apparent EC75 of K+ was similar for all the ages investigated. K(+) stimulated efflux of GLU and GABA was Ca++ dependent, but this was not the case for spontaneous GLU efflux. These data indicate that, in the guinea pig hippocampus, the GLU neuronal system is developing throughout gestation, whereas the GABA neuronal system appears to mature before the brain growth spurt. PMID- 1307101 TI - [Reliability of preclinical tests--predictability of results in man based on studies in laboratory animals]. PMID- 1307102 TI - [Clinical pharmacology of amiodarone]. PMID- 1307103 TI - [Arrhythmogenic function of antiarrhythmic drugs]. PMID- 1307104 TI - [Interactions between propranolol, isosorbide and nitroglycerin]. AB - We studied interactions between propranolol and nitrates, used in subjects with stable angina pectoris on effort. Basal pharmacokinetic indexes were estimated on measured levels of propranolol concentration. It was found, that nitrates used with propranolol at the same time decrease its concentration in serum and bioavailability, and increase propranolol clearance calculated for whole body, its distribution volume and shorten propranolol life half-time in the blood serum. PMID- 1307106 TI - [Organic nitrates--new approach to therapy]. PMID- 1307105 TI - [Endogenous cardiac glycosides]. PMID- 1307107 TI - [Pharmacotherapy of allergic diseases]. PMID- 1307108 TI - [Clinical and cytologic evaluation of flunisolide--corticosteroid local action on nasal mucous membrane in women]. PMID- 1307109 TI - [Omeprazole in treatment of patients with recurrent duodenal ulcer]. PMID- 1307110 TI - [Pharmacokinetic and pharmacodynamic basis for treating neoplasms in elderly patients]. PMID- 1307111 TI - [Pharmacokinetics of methotrexate]. PMID- 1307112 TI - [Clinical pharmacology of cyclosporine]. PMID- 1307114 TI - [Fantasies after drug therapy as an undesirable effect of benzodiazepine (warning to physicians)]. PMID- 1307113 TI - [Disturbances of vision as an effect of drug adverse reactions]. PMID- 1307115 TI - [Concentrations of trace metals in Ariopsis bonillai (Pisces: Siluriformes) of Santa Marta, Colombian Caribe]. AB - To determine changes in the contents of some heavy metals (Cd, Zn, Cu) in the fish Ariopsis bonillai, at Cienaga Grande de Santa Marta, Colombia, monthly samples were taken between July 1987 and June 1988. The highest concentrations in the muscle appear between November and February (4.24 micrograms Cd/g, 109.4 micrograms Zn/g and 13.3 micrograms Cu/g), during the periods of lower salinity, at the end of the rainy season, and at the beginning of the dry season. Metals were measured also in the liver: values for Zn and Cu were ten times higher than in the muscle. About the first half of the year, the values tend to be similar. Cd differences were not as strong as for the other metals. PMID- 1307116 TI - Characterization of a proteolytic enzyme from Lachesis muta venom (Serpentes: Viperidae). AB - A proteolytic enzyme from L. muta stenophrys was isolated by gel filtration on Bio Gel P-100 followed by FPLC on MONO S column. The enzyme exhibited proteolytic activity toward casein, hemoglobin and fibrinogen with a pH optimum around 10. The activity was inhibited by EDTA while trypsin inhibitors were not inhibitory. It is a glycoprotein, Mr 14 kDa with a high content of Asp, Glu, and Leu residues and a low content of Cys and Trp. The protease is devoid of myotoxic, hemorrhagic, esterolytic and amidolytic activities. It lyses the alfa and beta chains of human fibrinogen and releases kinin from L.M.W. kininogen. No release of histamine was observed upon incubation with mast cells. PMID- 1307118 TI - [Ultrastructure of mucous cells from the oviduct epithelium of the rabbit (Lepus cuniculus). Preliminary study]. AB - Authors studied the ultrastructural features of the mucous cells present in the three segments of the rabbit oviduct in anoestrous. Results showed that only one kind of mucous cell was present in the isthmus while two different kinds of mucous cells were found in the ampulla and infundibulum. The ultrastructural features observed in the isthmic cells correlated well with the histochemical data already described in that segment. However such correlations could not be made between the ampulla and infundibulum. Authors suggest that the ampulla can be considered a transitional segment between isthmus and infundibulum. PMID- 1307117 TI - [Isolation of Vibrio cholerae no-01 in the Gulf of Nicoya, Costa Rica]. AB - In a bacteriological study on samples of bivalves, mud and surface waters from the Gulf of Nicoya, Costa Rica, 18 strains of non-01 Vibrio cholerae and 50 of V. mimicus were isolated. The samples were enriched in alkaline peptone water, and streaked on MacConkey and inositol-brilliant green bile agars. Biochemical and serological tests were used for their identification. Both species were isolated from all sampling sites (Lepanto, Jicaral and Puntarenas) with either of the two agar media, even though these were not specific for vibrios. PMID- 1307119 TI - [Number and thickness of myelinic fibres of the phrenic nerve of young and aged rats]. AB - The phrenic nerve of albino rats was studied for age changes in number of fibres, myelin sheath thickness and axon calibre. There is no significant morphological differences between nerves from young and aged rats and no difference with age was found in the number of fibres, myelin sheath thickness and axon calibre. PMID- 1307120 TI - [Early care of the newborn infant]. PMID- 1307121 TI - [Respiratory distress syndrome in the newborn infant]. PMID- 1307122 TI - [Follow-up of high-risk newborn infants]. PMID- 1307123 TI - [Neonatal bacterial infections]. PMID- 1307124 TI - [Surgical problems of the newborn infant]. PMID- 1307125 TI - [Problems in the premature newborn infant]. PMID- 1307126 TI - [Newborn infant transportation]. PMID- 1307127 TI - [Structure of neonatal intensive care units]. PMID- 1307128 TI - Normal host defenses and impairments associated with the delayed resolution of pneumonia. AB - The lung is constantly exposed to infectious challenges and depends on a complex system of defense mechanisms to facilitate the clearance of pathogens and prevent the development of infection. Both the upper airway and lower respiratory tract have mechanical, humoral, and cellular mechanisms in place to protect the airways from diverse microorganisms. Impairment in any arm of this system can result in the predisposition of the host to respiratory infections, which may be of a recurrent nature. Defects may be congenital or acquired, and may be iatrogenic in the hospitalized patient. An understanding of these defects may lead to more effective therapies and preventive modalities for decreasing the number and severity of respiratory infections. PMID- 1307129 TI - Normal resolution of community-acquired pneumonia. AB - Resolution of pneumonia has to be considered as two different phases: resolution of the acute illness and resolution of radiographic opacities. Age, comorbidities, immunosuppression, and etiological agent(s) are all important in determining whether the acute illness resolves; there is a considerable mortality rate from pneumonia requiring hospitalization. The major concern when there is slow radiographic resolution of pneumonia is the possibility of an underlying malignancy. In 96% of patients whose pneumonia has not resolved in 30 days, an underlying disease is found; emphysema, chronic bronchitis, or bronchogenic carcinoma are the most common. Normal resolution of community-acquired pneumonia has to be defined in terms of the severity of the illness, comorbidity (ies), and infecting pathogen(s). PMID- 1307130 TI - Definition and evaluation of the resolution of nosocomial pneumonia. PMID- 1307131 TI - Chronic and recurrent pneumonia. AB - Recurrent pneumonia is defined as two or (usually) more separate episodes of lower respiratory tract infection that generally are accompanied by fever, leucocytosis, and purulent sputum production. These episodes are separated by an asymptomatic interval of at least 1 month or clearing of the chest visible by radiograph. Clinical improvement and radiological clearing should result after appropriate antimicrobial therapy. Chronic pneumonia is an illness that lasts at least 6 weeks and is caused by a microorganism. The chest radiograph usually shows diffuse or focal shadows. The incidence of either chronic or recurrent chest infections is unknown. Neither condition is common, but when present, they frequently present a difficult diagnostic challenge. Chronic pneumonias are usually caused by slow-growing organisms, such as fungi or mycobacteria. Occasionally, chronic pneumonias cannot be diagnosed, even when lung biopsy specimens are cultured or studied histopathologically. When a patient presents with recurrent pulmonary parenchymal infections, the clinician needs to identify the likely etiologies. Possible etiologies are structural abnormalities, underlying medical conditions, and immunological abnormalities, including infection by the human immunodeficiency virus (HIV). PMID- 1307132 TI - A practical approach to nonresolving pneumonia. PMID- 1307133 TI - Atlanto-axial dislocation in children. AB - The authors present 14 cases of C1 C2 dislocations in children (8 boys and 6 girls; mean age, 6.9 years) seen at the Orthopedics and Traumatology Institute of the University Hospital, Faculty of Medicine, University of Sao Paulo from 1978 to 1990. In view of the disappointing results obtained by conservative treatment in 6 of the 14 patients, the authors recommend early atlanto-axial arthrodesis in cases of C1 C2 dislocation in children. PMID- 1307135 TI - Isolated vertebral blocks in the cervical spine. AB - The author presents a review of seven cases with isolated vertebral block of the cervical spine, studied in 1980 in order to verify if the etiology was congenital or acquired. This kind of bony alteration of the spine confused in the literature with Klippel-Feil's syndrome, which is a congenital constellation of bone alterations. The author concludes that, even in two cases with a diagnosis of rheumatoid arthritis, the vertebral block probably was not related to the inflammatory pathology. For one case of severe rheumatoid arthritis, it is proposed that the congenital block may have been present before the onset of the inflammatory disease. The cervical vertebral block can be considered to be an asymptomatic radiological finding. PMID- 1307134 TI - Study of anatomical bases of a latero-dorsal flap of the forearm preserving the radial artery. AB - The authors studied the dorso-lateral cutaneous branches of the radial artery in 26 forearms of fresh cadavers following injection of latex. Three to eight branches were identified, with frequent anastomoses. Extensive venous drainage was also observed. One to three cutaneous branches arose within a 3-cm region close to the radial styloid precess. This provides a basis for an island flap supplied by these branches and thus, it is possible to maintain the radial artery intact. PMID- 1307136 TI - Finger replantation. AB - The objective of this study was to determine the influence of the following factors on the survival rate of replanted digits: patient's age, type and level of amputation, time of ischemia, number of arteries and veins anastomosed and type of vascular repair. A total of 60 digits were replanted by the author from 1980 to 1990. The results showed no significant correlation between the survival rate and the factors studied. However, the surgeon's experience played an important role in the survival rate of replanted digits. PMID- 1307137 TI - Sex variation at the time of sonographic appearance of the proximal tibial epiphyseal ossification center. AB - The time of sonographic appearance of the proximal tibial epiphyseal ossification center and its sexual variation was assessed in 659 normal pregnancies. Proximal tibial center appears between 34-37 weeks gestation. In female fetuses, it appears between 34-35 weeks and in males, between 35-36 weeks (P < 0.001). There was a tendency of female proximal tibial center appearance to precede male appearance, by approximately one week. This difference, however, didn't show statistical significance. PMID- 1307138 TI - Heart murmur in pediatrics: innocent or pathologic? AB - In a sample of 256 children referred to the Sao Paulo Hospital for consultation because of heart murmurs the incidence of innocent murmur was 41%. A clinical history and physical examination was performed in every child. The diagnosis was confirmed without the use of laboratory tests in only 5.5% of the cases: 32% of the children were submitted to chest x-ray and electrocardiogram; an echocardiogram had to be performed in 61% of the children and in 1.1% the catheterism was necessary to make the diagnosis. In the great majority of children with high suspicion of innocent murmur a good history and physical examination will suffice to confirm the diagnosis. If heart disease is suspected, laboratory tests should be performed for further evaluation. Any physician should be able to distinguish between pathologic and innocent murmurs based on their clinic features. The authors present a short review about the subject. PMID- 1307139 TI - Utilization of cytogenetic technics in paternity investigation. AB - The joint analysis of several genetic markers in cases of paternity investigation renders possible a cumulative probability of 99.7% of chance of exclusion of a falsely accused father. The role of heteromorphisms of the Y chromosome size was appraised in this work, with more than one genetic marker, in 20 expertise examinations in paternity investigation, where the children were male. The results found with this method, in association with the research on erythrocytic and leucocytic antigens showed the exclusion of two falsely accused men. Cytogenetics analysis with Giemsa stain in combination with leukocyte (HLA system) and erythrocyte antigens investigation demonstrated the exclusion of two men falsely accused. PMID- 1307140 TI - Splenic viability after segmental devascularization. AB - The terminal vascular architecture is related to the segmental pattern of this organ. However, several interlobar vascular anastomoses communicate the spleen parts. In order to verify the efficacy of those anastomoses, the present work studied experimentally the viability of the spleen after selective external devascularization, in rats and dogs. All animals developed segmental necroses and eventual abscesses limited to the devascularized portion of the organ. These results demonstrate that the intraparenchymatous anastomoses do not maintain the viability of externally devascularized regions of the spleen. The data presented in this paper are worth to be considered in therapeutic conservative splenectomies. PMID- 1307141 TI - Common variable immunodeficiency: a clinical and laboratory evaluation of 15 cases. AB - The clinical and laboratory data for 15 patients with common variable immunodeficiency (CVI) (5 females and 10 males aged 3 years and 6 months to 40 years at first examination) were evaluated. The age of onset of infectious signs and symptoms ranged from 6 months to 35 years. Recurrent pulmonary infections predominated (86.6%), followed by chronic diarrhea (46.6%). Approximately 60% of the patients with pulmonary complaints presented chronic sequelae (bronchiectasis). Two developed a polymyositis-like picture. No neoplasms were observed. All patients presented immunoglobulin levels below 300 mg/dl and absence of antibody responses to poliovirus and to hemagglutinin. Two patients were negative when tested for autoimmunity. Cell immunity tested by the lymphoproliferative response in the presence of phytohemagglutinin was normal in 11 patients and depressed in 4. A decrease in the helper T population and inversion of the OKT4/8 ratio occurred in 13. Cimetidine treatment (1200 mg/day) applied to 5 patients for 4 weeks did not produce any clinical or laboratory improvement. Gamma globulin is the treatment of choice for these patients. PMID- 1307142 TI - Study of the inclination of the joint line in supracondylar osteotomy of the femur for valgus deformity. AB - The inclination of the joint line after supracondylar osteotomy of the femur for valgus deformity was studied in 22 patients and 26 knees. The patients (4 males and 18 females) were 17 to 77 years old (mean, 49.5 years). The obliquity of the joint line was measured in positive degrees (medial inclination) and negative degrees (lateral inclination). Mean obliquity was +3.1 degrees in the preoperative study and -2.0 degrees in the post-operative study. Significant horizontality of the joint line was obtained when the two periods were compared (mean, 5.0 degrees). PMID- 1307144 TI - [The determination of human mandibular deformations by using optical holography]. AB - A scheme of holographic investigation in counter-current bundles was used to study mandibular deformations in functional exercise. He-Ne laser LGN-215, generating was used as a source of light. To record the holographic interferograms, high-resolution plates of the PFG-03 type were employed, fixed directly on the object. The findings evidence that in contractions of the anterior and posterior masticatory muscles the mandible is exposed to deformation in the horizontal and frontal planes, most marked near the teeth and alveolar process. The deformation near the angle is more marked than in the chin area. PMID- 1307143 TI - [The relationship between the fluoride level in the jaw and the metabolic activity of the "supporting skeleton"]. AB - Experiments with 118 rats revealed a reduction of fluorine levels in the jaw and the symmetrical femoral bone in reduced metabolism due to hypodynamia, elevated metabolism due to femoral bone injury, and in combination exposure. These findings should be borne in mind when prescribing fluorine. PMID- 1307145 TI - [Morphological changes in the tissues of the prosthetic field with the use of different designs of metal ceramic bridge dentures]. AB - The results of experimental morphologic studies carried out in 23 dogs evidence that the status of the denture bed tissue beneath a whole-cast bridge cermet denture depends on the tightness of the denture adhesion to the gingival mucosa. If the denture poorly adheres to its bed, no marked changes in the structural components of the gingiva and the underlying bone support are detectable. If the denture adheres tightly to the gingiva, marked inflammatory dystrophic and destructive changes develop both in the gingiva and in the alveolar crest bone tissue. A complex of structural changes in the epithelium, connective tissue base of the gingival mucosa, and alveolar bone crest were traced. The results evidence that inflammatory dystrophic changes in the gingiva augment and result in the development of erosive ulcerative elements in the gingiva in case of a prolonged tight adhesion of the denture to the denture bed; sometimes decubital ulcers may develop in the gingiva. The resorptive processes take place in the underlying bone tissue, causing like smooth resorption of bone matter or to lacunar resorption. Diffuse rarification of bone tissue is also typical of such cases. Excessive pressure of the denture body in case of its tight adhering to denture bed seems to be detrimental not only for the epithelium, but for deeper structures of the gingival mucosa and the underlying bone structures as well. PMID- 1307146 TI - [Changes in dentin permeability for microorganisms during caries treatment]. AB - Effects of a number of chemicals and of the time elapsed since the preparation on dentine permeability for microorganisms were under study. Dentine permeability was found the highest immediately after the preparation and after acid treatment. Potassium oxalate and calcium hydroxide reduced dentine permeability. PMID- 1307147 TI - [Mycobacteria in the development of periodontal foci of infection]. AB - A total of 162 samples of material from the periodontal foci of infection were examined microbiologically and morphologically to detect mycobacteria and their biologically changed variants. The regularities of the pathologic process development in periodontal tissues of subjects without tuberculosis were found to fully conform to the current concept of a latent tuberculous infection. The periodontal foci of infection may be regarded as reservoirs of persistent mycobacteria, whose main form, L variant, was detected in 71.6% of cases. Clinical and morphologic manifestations of periodontitis depend on the stability of the persistent mycobacteria L forms. PMID- 1307148 TI - [The laser therapy and laser acupunture of patients with chronic recurrent aphthous stomatitis]. AB - Laser therapy and laser acupuncture of the biologically active sites were administered to 24 patients with chronic recurrent aphthous stomatitis. The biologically active sites were selected individually with due consideration for the underlying somatic condition. Good results were achieved in the patients with the fibrous form of chronic aphthous stomatitis. Secretory and serum immunoglobulin levels were monitored over the course of laser treatment. PMID- 1307149 TI - [Phosphorus-potassium metabolism in puerperae with late toxicosis and its correlation with the status of the maxillodental system]. AB - A deficiency of mineral components in the breast milk and saliva and shifts in the protein, carbohydrate, and lipid metabolism are observed in puerperae with a history of late gestosis; this fact tells negatively on the maxillodental system of the mother and her baby. PMID- 1307150 TI - [The therapy of inflammatory diseases of the maxillofacial area with the use of imidazole derivatives]. AB - Qualitative and quantitative composition of associations of the agents of odontogenic infection were studied making use of present-day bacteriologic methods and of analysis of the microflora sensitivity to trichopol and nitazole, imidazole derivatives. The microflora was found to be represented by associations with the predominance of obligate and facultative anaerobes. The anaerobes were found highly sensitive to trichopol, both in vivo and in vitro, and even more so to nitazole, the drug manufactured in this country. PMID- 1307151 TI - [The kinin system indices in the blood of patients with phlegmons of the maxillofacial area]. AB - Blood plasma initial protamine-splitting activity, levels of prekallikrein, fast and slow kallikrein inhibitors were measured in patients with maxillofacial phlegmons making use of K. N. Veremeenko's method. All these parameters were found changed in the patients on the day of their hospitalization; on days 5-7 of treatment a trend to their normalization was observed, the differences between these values in the patients and normal controls becoming insignificant. The kinin system activation reflected the severity of the patients' condition. PMID- 1307152 TI - [The efficacy of preparations with antioxidant action in the combined treatment of phlegmons of the maxillofacial area]. AB - The efficacy of hexamethylene tetramine (urotropin) was studied in 62 patients with maxillofacial phlegmons. The resultant good effect is explained by the pathogenetic action of the drug. The antiinflammatory effect of urotropin may be explained, on the one hand, by its known antiseptic effect, and, on the other hand, by its membrane-protective effect on the cellular elements, this creating the optimal conditions for the wound reparation. PMID- 1307153 TI - [The incidence and dynamics of the development of alveolitis over the course of a year]. AB - Analysis of the results of 8019 operations for removal of teeth, carried out within 5 years by one physician under the same conditions, has shown that alveolitis developed in 1.87 +/- 0.15% of cases, on an average. The risk of alveolitis was found the highest from December to March and the lowest from June to September, as evidenced by estimation of the index of the seasonal fluctuations in the morbidity (a total of 120 to 140 teeth were removed within a month, on an average). PMID- 1307154 TI - [The extracorporeal connection of a donor spleen in the treatment of suppurative diseases of the face and neck complicated by sepsis]. AB - Analyzes the results of extracorporeal connection of donor spleen in 9 patients with purulent diseases of the face and neck, complicated with sepsis. Presents the indications for the use of this treatment modality and its technique. Describes the changes in the clinical picture and time course of the basic homeostasis parameters over the course of therapy. Reduction of mortality rates to make them as low as 12.5% demonstrates a high efficacy of the suggested treatment as part of multiple-modality complex used in the treatment of odontogenic and surgical sepsis. PMID- 1307155 TI - [The x-ray picture of chronic odontogenic osteomyelitis of the mandible in adults in the past and today]. AB - Analysis of mandibular roentgenograms of 286 patients with odontogenic osteomyelitis has lead the authors to a conclusion on the predominance of diffuse forms of the condition with marked sequestration in the 30's and 40's. Currently hyperplastic osteomyelitis occurs in 12% of cases. PMID- 1307156 TI - [Our initial experience in treating mandibular fractures with wire splints placed on the lingual surface of the teeth]. PMID- 1307157 TI - [The results of the surgical treatment of fractures of the mandibular condyle in children]. AB - The results of surgical treatment of fractures of the mandibular condyle are analyzed in 36 children (39 surgeries) aged 3 to 17; 33 of the operations were carried out in fractures complicated with the dislocation of the condylar head. Reposition and osteosynthesis of the fragments were carried out in 17 cases, replantation of the condyle in 10, and arthroplasty of the temporomandibular joint in 12 patients. Good late anatomico-functional and esthetic results were achieved in 84.6% of cases; this is explained by a differentiated approach to the choice of surgical strategy, an effective system of rehabilitation measures, including early exercise, orthodontic treatment, and low-frequency electromyostimulation. PMID- 1307158 TI - [Vasodilator preparations in the combined treatment of mandibular fractures with disordered regional hemodynamics]. AB - A total of 130 patients with mandibular fractures of various sites were observed. One group of these patients were administered routine treatment, the other group patients were administered drugs improving the local circulation along with the physical modalities. Local circulation normalized two times sooner in this latter group, which fact accelerated the reparative processes and the treatment resulted in a sooner coalition of bone fragments and recovery of the working ability and functional parameters. PMID- 1307159 TI - [Age-related changes in the secretory function of the salivary glands]. AB - A total of 326 healthy subjects aged 21 to 80 were examined. Total sialometry without stimulation and that stimulated with supermint chewing gum was carried out. Mixed salivary secretion in health was found to make up approximately 3.4 ml in 10 min. Salivary secretion stimulation with the chewing gum enhanced this secretion 1.5-3 times. Salivary secretion was found to decrease with age. The maximal secretion levels were found in both men and women aged 21 to 30, being higher in men. Normal values of mixed salivary secretion of men and women can be estimated according to the following formulae: for men it is equal to [-0.09(X 25) +5.71] ml, for women to [-0.06(X-25) +4.22] ml, where X is the subject's age in years. PMID- 1307160 TI - [Mobilization of the facial nerve in surgical interventions in the parotid maxillary area (the topographic anatomical validation)]. AB - A method for facial nerve mobilization is suggested, developed on cranial preparations of adult subjects. The authors have distinguished characteristic topographic and anatomic regularities that are essential in surgery of the mastoid process and parotid-masticatory area for tumor or nontumorous involvement of the parotid gland in case of the facial nerve involvement in the process. PMID- 1307161 TI - [The need and possibility for disinfecting impressions in orthodontics (a review of the literature)]. AB - Reviews the data on a high risk of viral and bacterial infection of dentists in connection with the high prevalence of AIDS and viral hepatitis B and on the possibility of infection of dental patients and the staff by microorganisms transfer on the impressions. Presents the present-day methods and means for disinfection of the impression material. Emphasizes inadequate knowledge of the dentists about the virucidal efficacy and the possibility of the impressions changing their properties in disinfection, which fact results in inaccuracy of the ready articles. PMID- 1307162 TI - [The problems of dentistry]. PMID- 1307163 TI - [The possibilities for the objective assessment of the color of dental materials on the Quartz-4-type spectrophotometer]. AB - The authors analyzed the possibility of using the Quartz 4 type acoustic-optic spectrophotometer to identify the shades of stomatologic materials. Analysis of spectral aperture coefficient curves was carried out for 10 shades of plastics used to make permanent dentures Sinma-M. The authors came to the conclusion on the usefulness of such method of identification of the stomatologic material shades and even of the intermediate gradations of these shades. Using this method, it is possible to control the material surface color homogeneity. PMID- 1307164 TI - [The distal transposition of the premolars and molars in the adult maxilla]. AB - Clinical examinations of 100 patients and analysis of the diagnostic models of their jaws and teleroentgenograms of the head profiles (a total of 63 parameters were analyzed in 73 subjects) have revealed that distal transposition of the maxillary lateral teeth is indicated in their unilateral mesial transposition. There should be enough space for the teeth on the other side of the jaw in this case, and the median line between the central incisors should not be displaced from the center. An apparatus to carry out such transposition is suggested. The teeth were moved as far as 2 to 7.5 mm within 2.5-7.5 months. The late results are good. PMID- 1307165 TI - [A new approach to the use of sugar substitutes in dental caries prevention]. PMID- 1307166 TI - [The self-regulation of maxillodental anomalies in preschoolers and schoolchildren]. AB - The authors analyze the data that characterize the incidence and peaks of autoregulation of maxillodental abnormalities in 535 children aged 2 to 16. Autoregulation of deep occlusion was found to occur at the age of 4-7, of prognathic occlusion at 2-5, of the cross occlusion and of abnormalities of the position of individual teeth at the age of 7-10. PMID- 1307167 TI - [The indications for the surgical treatment of chronic periodontitis of the permanent teeth in children and adolescents of different health groups]. AB - Chronic granulating and granulomatous periodontitis of 250 permanent teeth was treated in children and adolescents aged 7 to 17, surgery had to be resorted to in 44 (18%) cases. Three groups of indications for radical treatment of chronic periodontitis in children were distinguished: difficulties in or impossibility of conservative treatment, inefficacy of conservative treatment, and somatic indications. The conservative and surgical methods together are most often indicated for patients in whom the adverse conditions of treatment (the first group of indications) are associated with an aggravated somatic status. Radical methods of treatment helped attain bone tissue recovery sooner (in 5-6 months) than after conservative therapy alone (in 8-9 months) and completely liquidate chronic foci of odontogenic infection. PMID- 1307168 TI - [Masticatory function in children in the early periods of the development of the bite]. AB - The authors suggest a test for accurate assessment of the masticatory function in subjects of various age groups. The results may be used as reference values in assessment of the function of the masticatory system in patients with various dental diseases. PMID- 1307169 TI - [The clinico-laboratory characteristics of the hard dental tissues in children born to multiparous women]. AB - A total of 900 children aged 3, 6, and 12 were examined. The findings evidence a lowered rate of salivary secretion and salivary levels of Ca and P, as well as a lower solubility of enamel for Ca and P in the children born fifth-eight. The incidence of dental hypoplasia and caries in these children was higher than in those born second in the family. Pregnancy aggravations (anemia, gestosis, etc.) in women who had had multiple deliveries and frequent diseases of their infants are the factors conducive to the reduction of dental resistance to caries and hypoplasia. The children born after multiple deliveries of their mothers should be referred to a risk group, and they should be observed by dentists and pediatricians since infancy. In regions with low fluorine levels in potable water antenatal caries prevention with fluorine preparations should be carried out. The program of comprehensive prevention of dental diseases should comprise both medical and social aspects. PMID- 1307170 TI - [The psychological aspects of the interrelations of dentist and patient from the viewpoint of the concept of D. Carnegie]. PMID- 1307172 TI - [An osteotome for the nose]. PMID- 1307173 TI - [Experience with the use of tests for the integration of teaching in a dentistry department]. PMID- 1307174 TI - [The 70th anniversary of the N. A. Semashko Moscow Dental Institute]. PMID- 1307171 TI - [An analysis of dental morbidity based on patient visits]. AB - The present-day system for assessment of the activities of dental clinics does not reflect their efficacy, for it does not take into consideration the population disease incidence and changes in this parameter. The author suggests that the incidence of dental diseases be assessed from the records of consultations at health institutions, as exemplified by a random sample of 2515 primary consultations at dental clinics. The cause of the consultation was classified in accordance with the International Disease Classification, 9th Revision. The author claims that such mode of assessment of the physicians' and clinics' work efficacy, will improve the quality of the diagnosis. PMID- 1307175 TI - [Dentistry in Russia under the conditions of insurance medicine]. PMID- 1307176 TI - [The needs of the population to be served for periodontal care]. PMID- 1307177 TI - [Mini-forum: rhinoplasty by external approach. Collumello-trans-alar approach of open rhinoplasty: advantages]. AB - For several years, the authors have been using a columellar transalar incision through the medial crus along the nasal septum, reaching the vault and continued laterally by a transalar cartilaginous incision. The nasal tip is thus opened like a car-hood, leaving the alar cartilage attached to the skin and exposing the triangular cartilage and the nasal septum. This approach allows septoplasty to be performed with excellent exposure. The tip is easily revised backwards allowing anomalies to be viewed directly. The advantages of this external approach compared with the classical external Rethi's approach are multiple: simplicity and rapidity of the technique, excellent access to triangular cartilages and the triangular-septum junction; possibility of always going from an endonasal approach to an external one and excellent access to the tip. Moreover, there is no long term swelling of the tip. The indications of this external approach are asymmetry of the tip, excessive tip projection, saddle nose deformities and secondary rhinoplasties. No complication has been observed in a series of 32 patients with a follow-up of 6 to 48 months. There is no disturbance of the tip position and the skin scar is imperceptible. PMID- 1307178 TI - [Miniforum: rhinoplasty by external approach. Technical aspects of rhinoplasty by external approach]. AB - The authors present the principle techniques of external transcolumellar rhinoplasty and stress the excellent exposure it provides, allowing effective treatment under direct vision of the anatomical structures of the nose tip, nasal spine and septum. Based on a series of 186 operated cases with a follow-up of between one and more than six years, the advantages and indications of this technique are briefly defined. The best indications are difficult nose tips, whether rhinoplasty is primary or, more particularly, when it is secondary. PMID- 1307179 TI - [Mini-forum: rhinoplasty by external approach. External or endonasal approach for rhinoplasty?]. AB - There appears to be a renewed interests in the external approach to rhinoplasty, first described 60 years ago, despite the external columellar incision, due to the excellent exposure of the cartilaginous structures provided by this approach. Progress has been made in rhinoplasty. Cartilage grafts are much more widely used than in the past and surgeons try to reconstruct a normal anatomy of the skeleton, which has become easier with this approach. However, the closed approach has demonstrated its efficacy for a long time and allows correction of a large range of deformities. The open rhinoplasty should not be the standard procedure and its indications should only be based on limitations of the closed approach. The external procedure is particularly indicated in some difficult cases of nasal tip surgery and secondary rhinoplasty. PMID- 1307180 TI - [Orbicularis oculi muscle and crow's feet. Pathogenesis and surgical approach]. AB - Crow's feet is one of the characteristic signs of the aging face. Minor techniques designed to obliterate these lesions rapidly demonstrate their limits. The orbital fibers of the orbicularis oculi muscle play a fundamental role in the pathogenesis of wrinkles. Their contracture will create wrinkles in a similar way to the spokes of a wheel perpendicularly to the orientation of the muscle fibers. The dynamic action of the zygomatic muscles contributes to exaggerate these wrinkles. Statically, ptosis of the lateral brow and the aging skin also contributes to these lesions. Surgical treatment can be accomplished by a temporal lift or via a blepharoplasty approach. The vertical fibers of the orbicularis oculi muscle must be corrected by muscle incision or resection, muscle incision and suspension, muscle redraping and fixation, covering of the orbicularis oculi muscle with the malar SMAS. In patients with ptosis of the tail of the eyebrow one must either do a forehead lift or a mask-lift that will redrape the skin. The surface of the skin may require peeling by dermabrasion. Of course, these surgical techniques require a detailed knowledge of the anatomy of this region and especially the distribution of the branches of the facial nerve. The author analyses and compares the results of the different techniques. PMID- 1307181 TI - [Preservation of the hairline in cervicofacial lift by double temporal and retroauricular rotation flap]. AB - The author details in this paper the techniques he uses to limit the sequelae of face lifts in terms of hair displacement. A temporal rotation flap to avoid hair elevation in the preauricular area, with resection of a de-epithelialized triangle and an L flap in the retroauricular area to reconstruct the hairline continuity. PMID- 1307183 TI - [Effect of inadequate filling of deflation of inflatable breast prostheses. Statistical study of 535 inflatable prostheses]. AB - This study was based on a series of 535 inflatable prostheses used for breast reconstruction or augmentation with a mean follow-up of 5.15 years. The authors specifically analysed the statistical correlation between underinflation and deflation due to late rupture. They demonstrated a statistically significant difference between the initial filling of the prostheses which subsequently deflated and the initial filling of all prostheses of the series. The mean filling of prostheses which subsequently deflated was 89% while the mean filling of all prosthesis in the series was 100%. The various pathologies are analysed according to the cosmetic or reconstructive indications. The two series, cosmetic and reconstructive, were homogeneous in terms of filling volume and deflation; the only difference concerned the age distribution. Patients undergoing breast reconstruction with a prosthesis were older than patients undergoing augmentation surgery for small breasts. The authors discuss the advantages and disadvantages of this type of prosthesis. PMID- 1307182 TI - [Use of the free latissimus dorsi flap in the reconstruction of extensive orbital exenterations]. AB - The authors present the use of a free latissimus dorsi myocutaneous flap for closure of large orbital exenterations. Five cases illustrate different tumor involvements and coverage possibilities. Several technical details are studied. The vascular anastomoses are performed on cervical vessels: external carotid artery internal jugular vein. The latissimus dorsi myocutaneous flap is particularly suited for reconstruction of large facial soft tissue defects around the orbit when obliteration of the orbital cavity and restoration of deficient facial skin are necessary with correct morphological results. PMID- 1307184 TI - [Immediate breast reconstruction by musculocutaneous flap]. AB - Immediate breast reconstruction (IBR) after mastectomy is now quite frequent. To achieve this, an implant, in a complete muscular pocket, or a myocutaneous flap (latissimus dorsi, TRAM flap) can be chosen. Since 1983, 49 immediate breast reconstructions (11% of IBR) were performed with a myocutaneous flap in the Gustave Roussy Institute. In our experience, these techniques were principally performed because of the failure of conservative treatment (70%). Immediate complications were more frequently observed after immediate breast reconstructions with a TRAM flap (partial or minimal flap necrosis: 33%, infection: 13.5%). Late complications were more frequent in reconstructions with a latissimus dorsi flap: the prostheses were the main reasons (contracture III/IV: 25%, infection: 18%, deflation of the implant: 12%). The best long term results were described with the TRAM flap, and we now prefer this technique for immediate reconstruction with a flap. PMID- 1307185 TI - [Partial subfascial abdominoplasty. Our technique apropos of 36 cases]. AB - With the help of a liposuction performed behind the abdominal superficial fascia, followed by a dissection first located at the deep side of this fascia, then changing plane to the level of the umbilicus to reach the premuscle fascia plane, a new abdominoplasty is performed, that ensures safer vascularisation of skin and fat as well as better preservation of the lymphatic system. In our experience (March 1989, 36 cases), this technique avoids the most frequent risk of the abdominoplasty: seroma. PMID- 1307186 TI - [Reconstruction of distal loss of substance in the nail-bed by a de epithelialized flap from the digital pulp]. AB - Twelve patients, presenting with traumatic avulsion of the distal nail bed, repaired by a de-epithelialized palmar advancement flap, were reviewed with an average follow-up of 23 months. Subjective results were considered excellent in two cases, good in seven, fair in two and poor in one patient. Nail adherence with the de-epithelialized flap was observed over almost 90% of the new nail bed. Nail dystrophy was observed in three patients, but was severe in only one. Two patients had slight curvature of their nail, while one had a severe hook-nail deformity. Mobility in the finger was always complete, and only one patient had a slightly decreased two-point discrimination on the flap. PMID- 1307187 TI - [Value of a free osteocutaneous flap from the second metatarsal bone in the management of substance loss in the forearm, caused by gunshot wounds. Apropos of an experience in 28 cases]. AB - The authors report their experience of the secondary treatment of forearm defects secondary to gunshot injuries. The lesions encountered involved both soft tissues and bone. After using classical techniques consisting of fibula or iliac crest osteocutaneous free flaps, they used, whenever possible, a second metatarsal osteocutaneous free flap, which enabled them to conduct a comparative study of these different procedures and they concluded on the superiority of this latter type of flap. Their experience is based on 28 cases, including 16 cases of second metatarsal osteocutaneous free flap. PMID- 1307188 TI - [Choice of technique in covering an excision of neoplastic tissue in the inguinal area]. AB - Cancer surgery of the groin may lead to large skin resection with exposure of the femoral vessels. A reliable coverage technique must be chosen to enable this kind of surgery. Six patients were operated on, and ten flaps were used (3 omentum - 3 rectus abdominis - 1 fascia lata - 1 gracilis - 2 latissimus dorsi free flaps). In the light of our results, omentum must be used when laparotomy is associated with inguinal resection and omentum is available. In the other cases, resection size could prohibit the use of local flaps and a contralateral rectus abdominis flap is chosen which allows coverage of the inguinal area down to the middle third of the thigh. PMID- 1307189 TI - [Goyrand J.G.B (1803-1866), surgeon and academician from Aix en Provence]. AB - The authors present Jean-Gaspard-Blaise Goyrand, from Aix, who is not simply remembered for his description of the wrist fracture which has retained his name. His theses concerning permanent retraction of the fingers, presented to the Royal Academy of Medicine in 1833 and 1834, were contrary to those proposed by Dupuytren and proved to be completely accurate. All of Goyrand's work was edited by Masson in 1870, including a superb case report of giant elephantiasis of the penis and scrotum, a study on cleft lip and the technique of using collodion bands to close large wounds [corrected]. PMID- 1307190 TI - [Experimental models of torsades de pointes]. AB - Several experimental models of torsades de pointes have been proposed these last years. They can be classified in 2 categories: morphological models designed to reproduce the ECG features of "torsade", with in vivo ventricular stimulations or with computer ECG stimulations and pharmacological models designed to obtain in vivo early after depolarizations, with toxic agents such as cesium chloride and anthopleurine, or with commercialized or new pharmaceutical drugs. These models improved electrophysiologic and pharmacologic knowledge of torsades de pointes. The respective roles of early after depolarizations in torsades initiation and of reentry in the following beats of the salvos is now recognized. Induction protocols were described, which appeared to involve an inotropic potentiation following burst or repetitive extrastimuli. A more accurate evaluation of arrhythmogenic risk associated with new drugs could be developed. PMID- 1307191 TI - [Clinical aspects of polymorphic ventricular tachycardia]. AB - Polymorphic ventricular tachycardia is defined as constant change of the QRS morphology. The diagnosis has important etiological, therapeutic and prognostic implications. This term covers several different entities which may be artificially distinguished by the electrocardiographic appearances during tachycardia, by changes of the resting electrocardiogramme, the mode of onset, the presence or absence of underlying cardiac disease and of intercurrent drug therapy. However, as the resting ECG may not be available in an emergency situation, or difficult to interpret, the clinical context is the key to diagnosis and treatment. Polymorphic ventricular tachycardia is classified according to the absence or presence of underlying cardiac disease respectively as torsades de pointe with long QT, torsades de pointe with a short coupling interval and catecholamine-induced ventricular tachycardia of childhood on the one hand, and, iatrogenic torsades de pointe, ventricular tachycardia in acute or chronic infarction and other cardiac diseases, on the other hand. Finally, the authors discuss the problem of polymorphic ventricular tachycardia induced by programmed ventricular stimulation. PMID- 1307192 TI - Arrhythmia and hypertrophic cardiomyopathy. AB - Atrial fibrillation is the commonest arrhythmia observed in hypertrophic cardiomyopathy, and is associated with an acute deterioration in symptoms. Digoxin is the drug of choice in established atrial fibrillation and amiodarone the drug of choice in paroxysmal atrial fibrillation and ventricular arrhythmia. Non-sustained ventricular tachycardia occurs in 20% of patients and is the single best predictor of sudden death in adults. Sustained monomorphic ventricular tachycardia occurs only rarely. The mechanism of sudden death is likely to involve initiating factors such as arrhythmia and peripheral autonomic dysfunction causing haemodynamic instability and myocardial ischaemia. Myocardial disarray may provide the arrhythmogenic substrate such that haemodynamic instability and ischaemia results in ventricular fibrillation and sudden death. PMID- 1307193 TI - [Sinus variability: value of rhythmology]. AB - The study of heart rate variability is a mean of assessing the influence of the autonomic nervous system on the normal and pathological heart. It may be performed by temporal or spectral analysis over 24 hours or shorter periods. It is possible to define for each temporal or spectral analysis the components of the autonomic nervous system which influence these parameters. After myocardial infarction a decrease in heart rate variability indicates a poor prognosis. This post-infarction risk factor is relatively reliable compared with the other prognostic factors. A decreased heart rate variability is also observed in cardiac failure but the significance of this finding has not been established. Many other fields of application of the study of heart rate variability may be envisaged, in other cardiovascular pathologies, in the evaluation of cardiovascular therapeutic interventions or in the assessment of patients with non-cardiac pathology in which the autonomic nervous system plays an important role. A lot of research on heart rate variability is currently under way and many developments are expected in the next few years. PMID- 1307194 TI - [Electrocardiography of atrioventricular block]. AB - A functional physiological block protects the ventricles from the risks of excessively rapid atrial rhythms. Pathological AVB is classified in three degrees according to whether the ventricular excitation is delayed, intermittent or absent. The site of AVB can be accurately determined by endocavitary electrophysiological studies but can also be estimated from the surface electrocardiographic recordings. fundamental research has questioned the sle responsibility of conduction defects in Wenckebach and paroxysmal blocks: they suggest the presence of abnormalities of excitability in pathological zones. PMID- 1307195 TI - [Late ventricular potentials and myocardial infarction. A critical analysis]. AB - The identification of patients at high risk of developing severe ventricular arrhythmias or sudden death after acute myocardial infarction is one of the major preoccupations of cardiologists. In this field, electrocardiographic signal averaging represents a promising technique and the prognostic value of late potentials in the post-infarction period has been well demonstrated during the last 10 years. However, in order to use optimally the information obtained by this technique the limitations should be understood: what do late ventricular potentials represent from the electrophysiological point of view? Do they play an active role in the genesis of ventricular arrhythmias or are they only a marker? What is the best method of recording late potentials? What are the criteria of normality of signal averaged recordings? What is the predictive value of late potentials in the post-infarction period? At what moment should they be searched for? Are they affected by medical therapy? These are some of the questions which have not yet been answered and which are addressed in this article. PMID- 1307196 TI - [Radiofrequency treatment of junctional tachycardia]. AB - Atrioventricular nodal tachycardias due to intranodal reentry or to an accessory pathway are accessible to radical cure with radiofrequency currents applied either at the site of recording of characteristic slow potentials or at the tricuspid or mitral atrioventricular rings. One hundred and six patients with atrioventricular nodal reentry were treated by modification of the slow anterograde reentrant pathway with a 100% success rate and without any serious complications (especially atrioventricular block). One hundred and eighty six patients had one or more overt or latent accessory pathways and were treated by the same method. The ablation site was decided on indirect criteria and not by the recording of the specific activity of the accessory pathway. The success rate was 97%, also with no significant complications. The duration of the treatment was 41 +/- 22 min for the accessory pathways. The exposure time to ionising radiation was 14 +/- 14 min and 31 +/- 34 min respectively. These results suggest that the indications of radiofrequency current ablation could be extended. PMID- 1307197 TI - [Ventricular tachycardia caused by bundle branch reentry]. AB - Ventricular tachycardia by bundle branch reentry is a special type of ventricular tachycardia. A rare arrhythmia, it occurs in very particular conditions of ventricular dilatation and conduction defects. The diagnosis is based on electrophysiological findings associating a His potential preceding the ventriculogramme with a HV interval comparable to that observed in sinus rhythm, and spontaneous variations of the cycle length between two ventriculogrammes preceded by those of the His potentials. Contrary to what is observed in other forms of ventricular tachycardia, pacing is possible from the atrium without changes of the QRS complexes and the presence of fusion complexes excludes the diagnosis. Treatment consists of radiofrequency ablation of the right bundle branch. PMID- 1307198 TI - [Potassium channels and arrhythmia]. AB - Cardiac repolarisation depends mainly on the cellular extrusion of positive electrical charge related to the potassium ion through different channels. There are many potassium channels which are responsible for repolarisation in different cardiac tissues. Prolongation or shortening of the repolarisation period may be both antiarrhythmic and proarrhythmic depending on the given experimental conditions. Different potassium channels may be opened or blocked by clinically prescribed drugs. Activators of the iK(ATP) channels may exert antiarrhythmic effects by inhibiting activity induced by prolonged repolarisation. Experimentally, they may exert a proarrhythmic effect by predisposing to arrhythmias during myocardial ischemia. However, these effects have not been clearly demonstrated clinically. Potassium channel blockers may have an antiarrhythmic effect by reducing the variability of repolarisation, by prolonging the atrial and ventricular refractory periods and by their antifibrillatory actions. Nevertheless, they may have proarrhythmic effects resulting in triggered activation under particular conditions of bradycardia and/or ischemia. Examples of these effects have been reported in man. The understanding of the relationship between potassium channels and arrhythmias is particularly complex because of the multiple factors regulating the duration of repolarisation and the effects of drugs on this duration. These factors include the activity of the autonomic nervous system, the heart rate, ischemia and acidosis and the differences in response to endocardial and epicardial tissues. PMID- 1307199 TI - [Hepatic hemangiomas. The importance of the image]. AB - In the authors' experience, 0.24% of the patients submitted to liver imaging (ultrasound or computerized tomography) have hemangiomas. These are shown as solid nodular lesions, mostly found by chance. Sometimes they do not appear as typical solid vascular lesions. The authors' experience and the literature are discussed. A clear and concise approach to this benign neoplasm is suggested. PMID- 1307200 TI - [Inguinal herniorrhaphy with local anesthesia]. AB - We review five years experience on inguinal hernia repair under local anesthesia in a small hospital in the interior of the State of Sao Paulo, Brazil. Sixty patients were submitted to repair and they were evaluated according to their immediate results, kind of hernia, anesthetic and operatory techniques and recurrences. The results were considered excellent in 20% of the cases, good in 65%, regular in 13.3% and in 1.7% the results were bad. No recurrence was observed up to now. Most of the patients were discharged within 24 hours. The proposed technique has provided reduced hospital expenses and low risks of infection. PMID- 1307201 TI - [Celiac disease: report of 20 cases in Rio Grande do Norte, Brazil]. AB - This paper shows that celiac disease exists in Northeast of Brazil and can be one of the causes of malnutrition in the State of Rio Grande do Norte. The authors present a study of 20 cases of celiac disease in the State of Rio Grande do Norte where there had not been any cases diagnosed before 1978. Ethnic aspects in the State seem to have influenced the occurrence of the disease since the European miscigenation has been more frequent than that of negroes and local indians. The cases are analysed in this paper and correlated with the literature. PMID- 1307202 TI - [Prevalence of antibodies to hepatitis C (anti HCV) in blood donors in Rio de Janeiro, Brazil. Its relation to ALT and anti HBC]. AB - We have studied 933 volunteer blood donors from May to July, 1990. After a interview and screening tests for syphilis, Chagas disease, malaria and HIV, they underwent an enzyme immunoassay for HBsAg, anti HBc and anti HCV antibodies. Alanine aminotransferase (ALT) serum levels were determined by auto analyser. Most blood donors were male with mean age of 33 years (19-65). Anti HCV prevalence was 3.1% (29 from 933 blood donors). Among anti HCV+, blood donors, 44.8% (13/29) had ALT 40 UI/L, 31% (9/29) were anti HBc+ and 17.2% (5/29) had both surrogate markers simultaneously. From 109 donors with ALT 40 UI/L, 13 (11.9%) were anti HCV+, while among 153 anti HBc+ donors, the anti HCV was 5.8%. CONCLUSIONS: 1) we found a higher anti HCV prevalence among our blood donors than previous published reports from other countries; 2) our data show that surrogate assays do not adequately identify anti HCV blood donors, 41.4% of them would not have been excluded by anti HBc and ALT tests alone; 3) there were a correlation between anti HCV positivity with a sample to cutoff optical density ratio equal or greater than 4 and elevated ALT serum levels. PMID- 1307203 TI - [The lower esophageal sphincter in the elderly]. PMID- 1307204 TI - [Influence of age on lower esophageal sphincter pressure]. AB - We studied the effect of aging on lower esophageal sphincter (LES) pressure of 52 normal subjects, 129 patients with Chagas' disease and 63 patients with systemic sclerosis. Three groups were compared: with ages between 10 to 29 years, 30 to 49 years and 50 to 70 years. We used a perfused catheter and the station pull through (SPT) technique, at end expiratory phase. There was no difference in LES pressure between the three groups in normal subjects (p = 0.72) and patients with systemic sclerosis (p = 0.33). In Chagas' disease the patients with ages between 50 to 70 years had LES pressure (17 +/- 8 mmHg, mean +/- SD) lower (p = 0.03) than patients with ages between 10 to 29 years (22 +/- 9 mmHg). We conclude that in Chagas' disease the patients with ages over 50 years have LES pressure lower than patients with ages under 30 years, what does not happen with normal subjects nor systemic sclerosis patients. PMID- 1307205 TI - [Prevalence of the various types of gastritis in patients with upper dyspeptic symptoms]. AB - Multiple site biopsy specimens from 153 patients were examined retrospectively for the presence of gastritis and Helicobacter-like organisms (HLO). Chronic gastritis was classified as superficial gastritis, diffuse antral gastritis, postgastrectomy (reflux) gastritis, diffuse corporal atrophic gastritis, and multifocal atrophic gastritis. In some cases technical problems did not make possible to define the type of chronic gastritis and we introduce the terms unclassified gastritis and minimal inflammatory changes to name those cases. In our opinion they represent superficial biopsies from cases of diffuse antral gastritis. Diffuse antral gastritis was found in 60% of patients followed by multifocal atrophic gastritis found in 20% of patients. HLO was searched in histological sections stained by a modified Giemsa stain. The typical curved bacilli were seen in the gastric mucus or closely attached to the top of superficial or foveolar epithelial cells in 83% of patients. Although we have noted high correlation between activity of chronic gastritis and infection by HLO such correlation was not possible between the degree of activity and the degree of infection. PMID- 1307206 TI - [Lymph node metastasis in early rectal tumors]. AB - Sixteen patients with early rectal carcinoma seen between January 1981 and May 1991 have been reviewed to determine the lymph node involvement (histopathological examination of the lymph nodes) and its implications for subsequent treatment. The mean age was 63 years (from 38 to 79; 10 male, six female). The site of the tumor was predominantly in the lower rectum (56.2%). The polypoid and flat-elevated ulcerated (IIa + IIc) subtype were detected in nine and seven lesions respectively. Sphincter-saving techniques were carried out in 62.5% of cases, and only five patients (31.2%) required Miles' operation. Neither postoperative complication nor death were noted. The mean follow-up period was 57 months (6 to 133 months). No recurrence or distal metastasis were found during this follow-up period. The results had shown close relation between the depth of submucosal invasion and IIa+IIc subtype lesions with lymphovascular infiltration. Although this kind of association was not accompanied by an increased number of involved lymph nodes, major surgical resection is suggested in such cases due to the risk of lymph node metastasis when invasion into the submucosa reaches the Sm1c level or deeper. PMID- 1307207 TI - [Colon adenocarcinoma with neuroendocrine and squamous cell differentiation. A case report]. AB - A tubular adenocarcinoma of the colon with solid area composed by small cells that was found by immunohistochemistry study using antibody to neuron-specific enolase (NSE) to possess neuroendocrine differentiation is related. In another areas of the tumor were visualized keratinizing squamous cells. The presence of neuro-endocrine and squamous cells features provide further evidence that neoplastic colonic cells have the capacity for multi-directional differentiation. The implications of this combination in relation to theories of tumor origin and differentiation and the prognostic significance of neuro-endocrine cells in malignant neoplasms of the gastrointestinal tract are discussed. PMID- 1307208 TI - Variation and physiological significance of basal gastrinemia in normal children. AB - The objective of the present study was to determine the variation of normal basal gastrinemia values in children of different age ranges. Basal gastrinemia levels were measured by radioimmunoassay in 30 normal children aged 2 months to 9 years divided into 3 groups: 1) 11 children aged 2 to 6 months; 2) 9 children aged 7 to 18 months, and 3) 10 children aged 20 month to 9 years. Basal gastrinemia levels varied from 11 to 533 pg/ml (mean = 138.47, SD = 131.56) and correlated significantly to the children's ages. Differences were not statistically significant between group I (mean = 191.82, SD = 116.26) and group II (mean = 186.11, SD = 161.65) but were significant between group I and group I and group III (mean = 36.9, SD = 17.67) and between group II and group III. The results demonstrate that basal gastrinemia levels of normal children are inversely correlated with age, the highest values being observed up to 18 months of age. A marked decrease in basal gastrinemia occurs thereafter reaching levels similar to those reported for adults. The authors speculate whether the hypergastrinemia observed in the present study may be indicative of an important physiological function of gastrin in the ontogenic development of the stomach. PMID- 1307209 TI - [Carcinosarcoma of the esophagus: diagnostic importance of partial endoscopic polypectomy]. AB - The clinical and pathological manifestations of a case of carcinosarcoma of the esophagus are reported. Barium swallow and endoscopy revealed a polypoid mass in mid esophagus. The tumor was large, pedunculated, covered by smooth mucosa with some erosions. Histologically the tumor was composed of a mixture of invasion keratinizing cells and intermingled bundle of spindle shaped cells resembling fibrosarcoma. The tumor was removed with surgery and did not show submucosa infiltration. It was not detected any metastasis or local recurrence during the 12 months follow-up period. The diagnosis was made by an endoscopic partial polypectomy. We conclude that partial polypectomy may be of value in preoperative diagnosis of esophageal polypoid mass. PMID- 1307210 TI - Pancreatic metastasis from renal cell carcinoma. AB - We report a case of renal cell carcinoma that metastasized to the pancreas 7 years after the initial excision. The primary and the metastatic tumors were histologically similar. Upper gastrointestinal bleeding was the leading symptom in the present case and the cause of the patient's death. PMID- 1307211 TI - [Treatment of early gastric cancer]. PMID- 1307212 TI - Comparative report on endoscopic and surgical treatment for early gastric cancer in elderly patients. AB - Two cases of elderly patients with similar early gastric cancers who were submitted to endoscopic and surgical treatment are presented as examples. Considering older patients as a sole group in the decision-making process we discuss the pros and cons of each therapy supporting efficacy and opposing side effects in order to maintain a reasonable quality of life. PMID- 1307213 TI - [Cytopathological test performed during colonoscopy in the diagnosis of colorectal stenosis]. AB - The etiological diagnosis for the colorectal strictures can be very difficult. With the colonoscopy, it was possible to obtain samples with direct vision of the lesion. Consequently, the cytologic efficiency improved, with similar or even better results than histopathology. In the present study (107 patients) it was used the cytopathology performed during colonoscopy. After a specimen was obtained, it was smeared on glass slide, fixed in 95% alcohol, stained by HE, and examined microscopically, with conclusions during the procedure. The results were compared and further correlated to the histopathology of surgical specimen or based on clinical follow-up in those case not submitted to operation. The results showed a striking degree of correlation between both exams. For the cytopathology there were no inconclusive results, false-negative were less frequent than with histopathology, and only one case of false-positive (rectal villus adenoma) was observed. Considering the type, localization and perviousness of the lesion, similar conclusions were drawn, and did not affect the results, except that there were more false-negatives in both exams when the lesions were impervious. The cytopathological and histopathological studies were both highly sensitive and specific for the diagnosis of carcinoma. In conclusion, cytopathology performed during colonoscopy is safe and efficient in the study of colorectal strictures, which contributes to improve the orientation of these patients. PMID- 1307214 TI - Iron, copper and alpha 1-antitrypsin deficiency in the liver of cirrhotic and schistosomotic patients. AB - While a number of studies investigated iron and copper storage or alpha 1 antitrypsin (A1AT) deficiency in the liver of patients with cirrhosis, we did not find any similar study in schistosomotic patients reported in literature. We investigated the storage of both metals and the A1AT deficiency in the liver of 72 cirrhotic and 27 schistosomotic patients (5 with the hepatointestinal and 22 with the hepatoesplenic form of the disease). Forty-four patients with cirrhosis were also alcoholic, and 28 were not. Iron storage was detected in 23 patients with cirrhosis (31.9%); among these 16 (36.3%) were alcoholic and 7 (25.0%) non alcoholic (the difference was not statistically significant). Thirteen (56.5%), 5 (21.7%) and 5 (21.7%) patients presented I-grade, II-grade, and III-grade iron storage, respectively. Copperstorage was detected in 24 cirrhotic patients (33.3%), 15 being alcoholic (34.0%) in contrast with 9 non-alcoholic patients (32.1%), a statistically non-significant difference. A1AT deficiency was observed in 2 patients with cirrhosis (2.8%), one with history of alcoholism. HBsAg and HBcAg in hepatic tissue were detected in 5 cirrhotic patients (6.9%), three of them with a history of alcoholism. Iron and copper storage and A1AT deficiency were observed in 3 patients with cirrhosis (12.5%), while iron storage and A1AT deficiency were found in 2 additional patients with cirrhosis (2.8%). The authors underline that neither iron nor copper storage nor A1AT deficiency was found in any schistosomotic patient. The authors discuss the possible importance of these data. PMID- 1307215 TI - [Two cases of severe cutaneous vasculitis with thrombocytopenia associated with hepatic cirrhosis: autoimmune and infective-inflammatory component with endothelial lesion and restrictive pulmonary pattern in one case]. AB - Two clinical cases of female patients with hepatic cirrhosis and autoimmune multisystemic involvement with infectious intercurrent are reported. Case 1 presented infective endocarditis and erysipelas on the left thigh. In the course of the clinical picture a cutaneous vasculitis developed in the same place together with autoimmune thrombocytopenia, leukopenia and pulmonary restrictive picture with inflammatory pattern. There are also elevate immune complexes and complement consumption. Case 2 presented erysipelas on the left thigh cutaneous vasculitis and complement consumption. In Case 1 the infective endocarditis was treated with antibiotic therapy during 4 weeks followed by 1 mg/kg corticoid (Prednisone) with thrombocytopenia and leukopenia reversion. Case 2 presented an improvement with antibiotic only. The relation between chronic liver diseases and systemic autoimmune phenomena is commented, special attention being paid to the cutaneous, hematological and pulmonary affection. PMID- 1307216 TI - Misunderstanding of "interaction" fuels unwarranted criticism. PMID- 1307217 TI - Use of tourniquets. PMID- 1307218 TI - Increased risk of bacterial endocarditis in inflammatory bowel disease. AB - PURPOSE: The purpose of this retrospective as well as prospective case-control study was to analyze a possible overrepresentation of inflammatory bowel diseases among patients with native valve endocarditis as well as the factors that predispose patients with inflammatory bowel disease to infective endocarditis. PATIENTS AND METHODS: Among 213 consecutive patients treated for proven native valve endocarditis, six (2.8%) had inflammatory bowel diseases (three with ulcerative colitis and three with Crohn's disease). Three patients with inflammatory bowel disease were from the retrospective group, and three were from the prospective group. The prevalence of inflammatory bowel diseases has been determined to be 0.0641% in the Dusseldorf area. RESULTS: On the basis of these data, a 44-fold overrepresentation of inflammatory bowel diseases among the 213 patients with endocarditis was calculated with a statistical significance of p much less than 0.001. CONCLUSIONS: Inflammatory bowel disease may be considered an independent risk factor for bacterial endocarditis. Reasons may be more frequent bacteremias as a result of the higher incidence of diagnostic and therapeutic interventions, as well as increased permeability of the damaged mucosa for bacteria and the therapeutic immunosuppression in patients with active inflammatory bowel disease. Prophylaxis for bacterial endocarditis should be carefully considered before expected bacteremias in patients with highly active inflammatory bowel disease even in the absence of cardiac factors predisposing to bacterial endocarditis. PMID- 1307219 TI - Cutaneous manifestations of gastrointestinal disorders. Part II. AB - The cutaneous manifestations of inflammatory bowel disorders, vascular disorders of the gastrointestinal tract, celiac disease, and bowel-associated dermatosis arthritis syndrome are reviewed. The significance of these signs, guidelines for their management, and investigations are discussed. PMID- 1307220 TI - Pimozide-induced depression associated with polyuria and polydipsia. PMID- 1307221 TI - The search for the new pineal gland. Brain life and personhood. AB - The concept of "brain life," sometimes offered as the criterion for determining when personhood begins, cannot tell us what we want to know about persons. Neurological facts will not automatically yield ethical conclusions. PMID- 1307222 TI - Nail biopsy. Indications and methods. AB - Nail biopsy is a safe and useful diagnostic procedure for many nail disorders when routine clinical and laboratory methods fail to produce a diagnosis. Prerequisites for nail biopsy are an understanding of the surgical anatomy of the nail, adequate anesthesia and hemostasis, and a nail abnormality for which histopathology can provide the diagnosis. Indications and methods for nail biopsy vary according to the site and type of pathology in the nail unit. Nail bed and perionychial biopsies can be performed easily and with minimal scarring. They are most commonly used to diagnose tumors as well as infectious and inflammatory disorders of the nail. The most important reason to biopsy the nail matrix is to make or exclude the diagnosis of melanoma in a patient with longitudinal melanonychia. Great care must be taken in nail matrix biopsy to minimize the risk of permanent nail dystrophy. PMID- 1307223 TI - Basket impaction at the pancreatic head. PMID- 1307224 TI - Is it time to say goodbye to thoracotomy for treatment of rheumatic mitral stenosis? PMID- 1307225 TI - An analogue approach to audit in anaesthesia. AB - The predicted outcome of anaesthesia and surgery was compared with the immediate outcome in 508 patients by means of two 100 mm linear analogue scales. The results were used to obtain a statistically based rule by which the anaesthetist may consistently select three groups of patients for audit: group 1, patients in whom immediate outcome of anaesthesia and surgery is worse than predicted; group 2, patients whose outcome is better than predicted; and group 3, the remaining patients. The rule, which is simply adapted to departmental audit, does not necessarily need a computer but is suited to the computer as it is numerically based. PMID- 1307226 TI - Bleeding varices in the elderly. PMID- 1307227 TI - Drug interactions with warfarin. PMID- 1307228 TI - Evaluation of a program to prevent head and spinal cord injuries: a comparison between middle school and high school. AB - This study was designed to test whether the Oregon THINK FIRST-Head and Spinal Cord Injury Prevention Program, developed for the high school audience and previously shown to have a beneficial effect, would have the same effect on students in middle school. During the spring of 1989, four schools (two high schools and two middle schools) participated. Two weeks before and after the presentation of the THINK FIRST program, 830 student questionnaires were distributed in classrooms. Questionnaire items were designed to measure knowledge, attitude, behavior, and demographic features. There was a significant difference between high school and middle school students on pretest knowledge (P = 0.0001). The average knowledge increase among all students was 0.81 correct responses (95% confidence interval: +/- 0.22) among 15 questions. The increment in knowledge did not differ significantly (P = 0.37) between high school and middle school students. One-way analysis of variance revealed no significant differences in pretest knowledge or knowledge increase associated with membership in Students Against Drunk Driving or acquaintance with someone having sustained a head or spinal cord injury. After the program, students were more likely to believe that there were actions they could take to keep from getting injured (P less than 0.0001). However, there was no change in self-reported seat belt use and most students reported that they "never" wore a bike helmet. The findings suggest that the THINK FIRST program is appropriate and beneficial for viewing by middle school-aged students. PMID- 1307229 TI - A survey of state insurance commissioners concerning genetic testing and life insurance. AB - Rapid advances in genetic testing have stimulated growing concern about the potential for misuse of genetic data by insurance companies, employers, and other third parties. Thus far, reports of genetically based discrimination in life insurance have been anecdotal. Reasoning that state insurance commissioners were likely to be aware of (1) the extent of current use of and interest in genetic tests by life insurers and (2) consumer complaints about insurance being denied because of genetic condition or because of genetic test results, we conducted a survey of that group. We received responses from 42 of the 51 jurisdictions. Our results suggest (1) that those who regulate the life insurance industry do not yet perceive genetic testing to pose a significant problem in how insurers rate applicants, (2) that life insurers have much legal latitude to require genetic tests, and (3) that so far few consumers have formally complained to commissioners about the use of genetic data by life insurers. PMID- 1307230 TI - The presence of two different infantile Tay-Sachs disease mutations in a Cajun population. AB - A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the beta-hexosaminidase A (Hex A) alpha-subunit exon 11 insertion mutation that is present in approximately 70% of Ashkenazi Jewish TSD heterozygotes. The mutation in the remaining allele was a single-base transition in the donor splice site of the alpha-subunit intron 9. To determine the origins of these two mutations in the Cajun population, the TSD carrier status was enzymatically determined for 90 members of four of the six families, and extensive pedigrees were constructed for all carriers. A single ancestral couple from France was found to be common to most of the carriers of the exon 11 insertion. Pedigree data suggest that this mutation has been in the Cajun population since its founding over 2 centuries ago and that it may be widely distributed within the population. In contrast, the intron 9 mutation apparently was introduced within the last century and probably is limited to a few Louisiana families. PMID- 1307231 TI - The Canadian National Breast Screening Study: opportunity for a rethink. PMID- 1307232 TI - Semen transmission of human immunodeficiency virus. PMID- 1307233 TI - Prospects for the treatment of obesity. PMID- 1307234 TI - Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. AB - BACKGROUND: The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing such during the periconceptional period. The extent to which folic acid supplementation can reduce the first occurrence of defects is not known. METHODS: We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. RESULTS: Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetus or infant had a neural-tube defect or congenital malformation) was known in 2104 women who received the vitamin supplement and in 2052 who received the trace element supplement. Congenital malformations were significantly more prevalent in the group receiving the trace-element supplement than in the vitamin-supplement group (22.9 per 1000 vs. 13.3 per 1000, P = 0.02). There were six cases of neural tube defects in the group receiving the trace-element supplement, as compared with none in the vitamin-supplement group (P = 0.029). The prevalence of cleft lip with or without cleft palate was not reduced by periconceptional vitamin supplementation. CONCLUSIONS: Periconceptional vitamin use decreases the incidence of a first occurrence of neural-tube defects. PMID- 1307235 TI - "Re-entry syndrome" after teenage international exchanges. PMID- 1307236 TI - The death of Bill C-203. PMID- 1307237 TI - An unusual case of postoperative hoarseness. PMID- 1307238 TI - Alfalfa cyclins: differential expression during the cell cycle and in plant organs. AB - Cell division in eukaryotes is mediated by the action of the mitosis promoting factor, which is composed of the CDC2 protein kinase and one of the various mitotic cyclins. We have recently isolated a cdc2 gene from alfalfa. Here, we report the isolation of two cyclin genes, cycMs1 and cycMs2, from alfalfa. The cycMs2 gene shows highest similarity to type B cyclins. In contrast, the predicted amino acid sequence of the cycMs1 gene shows similar homology scores to cyclins of all types (25 to 35%). Both genes are expressed in dividing suspension cultured cells but cease to be expressed when the cells enter stationary phase. In synchronized alfalfa suspension cultured cells, the mRNAs of cycMs1 and cycMs2 show maximal expression in the G2 and M phases. Transcripts of cycMs2 are found only in late G2 and M phase cells, an expression pattern typical for cyclin B genes, whereas cycMs1 appears with the onset of G2. This pattern indicates that alfalfa cycMs1 and cycMs2 belong to different classes of cyclins. In young leaves, expression of both genes is high, whereas in mature leaves no transcripts can be detected, indicating that the two cyclin genes are true cell division markers at the mRNA level. In other organs, a more complex expression pattern of the two cyclin genes was found. PMID- 1307239 TI - Understanding and evaluating chronic urinary incontinence. AB - Urinary incontinence is a geriatric syndrome of large proportions financially and psychosocially. It may be one of the most neglected ailments. An understanding of the anatomy and pathophysiology of the problem is necessary to creatively assess and treat individual cases. The physician should have in mind an orderly and reasonably complete classification of urinary incontinence and be familiar with the terms traditionally used to describe various mechanisms and phenomena related to the condition. Evaluation of patients involves a discriminating selection of studies and, at times, trials of therapy. A "bedside cystometrogram" may yield much information. PMID- 1307240 TI - Ethical issues described by NICU nurses arise from three areas. PMID- 1307241 TI - Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia. AB - Following reports of mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene in early-onset familial Alzheimer's disease, we screened exon 17 for new mutations in presenile dementia. The majority of the 105 patients screened had definite or probable Alzheimer's disease, but we also included atypical cases and some chronic schizophrenics. We identified a single abnormal case--a chronic schizophrenic with cognitive defects. Sequencing revealed a C to T nucleotide substitution which produces an alanine to valine change at codon 713. We were unable to detect the mutation in the remaining members of the original cohort nor in a further 100 chronic schizophrenics and 100 non-demented controls. Nonetheless, the position of the mutation in a critical portion of the APP gene suggests that it may well prove to be pathogenic. PMID- 1307242 TI - Hormones, genetic program and immunosenescence. AB - Immunosenescence is discussed in the context of an integrated immune neuroendocrine homeostatic network. Under this new perspective, immunologic decline during aging appears as part of a multilevel phenomenon which affects intracellular as well as systemic regulatory mechanisms. In particular, the experimental data suggesting that during puberty, sex and adrenal steroids trigger thymus involution by inducing extensive apoptotic death of thymocytes is briefly reviewed. Next, the evidence indicating that aging brings about a progressive disruption in immune-neuroendocrine integration and the possible role of this disruption in the occurrence of age-associated autoimmune phenomena is considered. Finally, the possible mechanisms by which the genome can determine life span as well as the potential involvement of the major histocompatibility complex in this process are discussed. PMID- 1307243 TI - Age-related changes in the expression of T cell activation antigens following phytohaemagglutinin stimulation. AB - The role of accessory cells (AC) in the temporal expression of several key T-cell activation-associated antigens has been studied in healthy aged subjects. Compared to responses seen in young adults, phytohaemagglutinin (PHA) induced weak proliferation in peripheral blood mononuclear cells from the aged and lower numbers of T cells expressing CD71, CD25, CD38 or HLA-DR. T cell responses to the monoclonal antibody OKT3, however, were normal. Whereas HLA-DR+ T cell numbers could be increased by raising the AC content (up to 50%) in cultures comprising purified T cells and graded numbers of autologous AC, CD25+ T cell numbers remained largely unaltered. Co-stimulation with PHA + phorbol myristate acetate in the absence of AC restored both proliferation and CD25 expression in the aged. These results indicate that T cells from the healthy aged show selective deficiencies in their capacity to respond to mitogenic stimuli and suggest that impaired PHA responsiveness is due, at least in part, to defective AC-derived signals. PMID- 1307244 TI - Poly(ADP-ribosyl)ation: its role in inducible DNA amplification, and its correlation with the longevity of mammalian species. AB - In this paper, we review our recent work on poly(ADP-ribosyl)ation and its relationships with DNA amplification and with the life span of different mammalian species. Poly(ADP-ribosyl)ation is a eukaryotic posttranslational protein modification catalyzed by poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30). This enzyme is strongly activated by DNA strand breaks and apparently plays a role in DNA repair and other cellular responses to DNA damage. Our data from two different cell culture systems for inducible DNA amplification strongly suggest that poly(ADP-ribosyl)ation acts as a negative regulatory factor in the DNA amplification induced by carcinogens. Furthermore, we could show a strong positive correlation between directly stimulated PARP activities in mononuclear leukocytes of 13 mammalian species and the species' maximal life spans. The hypothesis is raised that a higher poly(ADP-ribosyl)ation capacity of long-lived species might contribute to the efficient maintenance of genome integrity and stability over their longer life span. Finally, we could show that the selectively overexpressed PARP DNA-binding domain efficiently inhibits poly(ADP ribosyl)ation in a transdominant manner. This molecular genetic approach should permit further interventional studies on biological role(s) of poly(ADP ribosyl)ation without application of low-molecular-weight PARP inhibitors, thus avoiding any of their possible side effects. PMID- 1307245 TI - Mutations in the candidate gene for Norrie disease. AB - Recently, we and others have isolated a candidate gene for X linked Norrie disease (ND) which was found to be deleted or disrupted in several patients. As a prerequisite for the identification of point mutations in the ND gene we have established the exon-intron structure of this gene. In 17 unrelated patients and 15 controls, PCR products derived from the promoter region, exons 1 and 2 as well as the coding part of exon 3 were analysed with the single strand conformation polymorphism (SSCP) technique. In 12 patients altered PCR fragments were detected which were studied in detail by direct sequencing. Eleven different mutations were found, and all but one are likely to give rise to significant structural changes in the predicted protein. These findings, and the absence of functionally relevant base changes in healthy controls, emphasize the causal role of this candidate gene in Norrie disease and pave the way for reliable diagnosis and carrier detection. PMID- 1307246 TI - Unstable DNA may be responsible for the incomplete penetrance of the myotonic dystrophy phenotype. AB - Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat in a sequence encoding a cAMP-dependent protein kinase. The normal copy number of 5-35 repeats is exceeded in DM patients, with the size of the expansion broadly correlating with the severity of symptoms experienced. In most families reported, the unstable DNA sequence has increased in size on transmission to affected offspring, thereby providing a molecular explanation for the phenomenon of anticipation in DM, i.e. an increase in the severity of symptoms associated with an earlier age at onset of the disease in successive generations of a family. Here we present the first reported case of a family where the transmission of the affected chromosome from father to son is accompanied by a reduction in the size of the triplet expansion, such that it falls within the normal range. As the son remains asymptomatic, this type of molecular event may provide an explanation for the incomplete penetrance of the disease phenotype reported for this disorder. The implications for genetic counselling of DM families and the mechanistic considerations of the trinucleotide instability are discussed. PMID- 1307247 TI - The large non-collagenous domain (NC-1) of type VII collagen is amino-terminal and chimeric. Homology to cartilage matrix protein, the type III domains of fibronectin and the A domains of von Willebrand factor. AB - Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical segment flanked by non-collagenous domains, NC 1 and NC-2. In this study, we examined the domain organization of human type VII collagen through analysis of deduced amino acid sequences derived from cloned complementary and genomic DNAs, as compared to peptide segments derived from amniotic membrane type VII collagen. The results revealed that the peptide segments derived from the NC-1 domain of type VII collagen could be assigned to the 5' portion of the composite cDNA, indicating that NC-1 resides at the amino terminal end of the molecule. Several sub-domains with homology to adhesive molecules were also identified within NC-1. These protein domains may confer adhesive properties to NC-1, thereby facilitating the binding of type VII collagen to the lamina densa in the cutaneous basement membrane and the anchoring plaques within the dermis. PMID- 1307248 TI - Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease. AB - Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease. PMID- 1307249 TI - Autosomal dominant branchio-oto-renal syndrome--localization of a disease gene to chromosome 8q by linkage in a Dutch family. AB - Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder with variable clinical manifestations affecting branchial, renal and auditory development. Varying clinical expression of the disease between different families suggests that multiple loci may be involved. However, the possibility of genetic heterogeneity as the cause of clinical variability cannot be resolved until the gene(s) causing BOR syndrome are mapped. DNA from four generations of a family with autosomal dominant BOR syndrome have been typed with a series of genetic markers on the long arm of chromosome 8. Using two point linkage analysis, a significant lod score of Z = 4.0 at theta = 0.05 was obtained with the D8S165 microsatellite marker. Multipoint analyses with 8q markers place the gene for BOR between the markers D8S87 and D8S165. PMID- 1307251 TI - Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. AB - Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that the 'brain type' dystrophin transcript predominates in brain. Using in situ hybridisation with antisense oligonucleotides, expression of four distinct mRNAs in specific brain areas is demonstrated here; the 14 kb muscle-type and brain-type transcripts were found to coexist in cortical and hippocampal neurons and two new transcripts have been identified in dentate gyrus and cerebellar Purkinje neurons, respectively. The latter has a novel first exon which was isolated and sequenced from mouse and human, and which would encode a protein with a different amino-terminus from the known muscle- and brain-type isoforms. Mapping in human located this exon in a large intron between the muscle-type promoter and second exon of the dystrophin gene. This finding of four alternative transcripts regulated by different promoters in brain reveals a new complexity to dystrophin expression that may have important insights for mental retardation mechanisms. PMID- 1307250 TI - Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome. AB - The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and five PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions. PMID- 1307252 TI - Segregation of the fragile X mutation from an affected male to his normal daughter. AB - We report here a family in which the fragile X mutation segregates from an affected grandfather through his normal daughter to an affected grandson. The grandson shows clinical and cytogenetic expression of fragile X syndrome due to a full mutation (large methylated insertion) in the fragile X gene (FMR-1). The mother shows a premutation (small unmethylated insertion) in her FMR-1 gene as the sole manifestation of the fragile X syndrome. The grandfather expresses the fragile X syndrome at the clinical and cytogenetic level, whereas he is mosaic for a methylated full mutation and an unmethylated premutation. The absence of expression of the fragile X mutation when transmitted through an expressing male might present further evidence for genomic imprinting of the FMR-1 gene. Alternatively, it is possible that the grandfather transmitted his premutation to his daughter due to germline mosaicism with both the premutation and the full mutation present in his sperm. PMID- 1307253 TI - Detection of a nonsense mutation in the dystrophin gene by multiple SSCP. AB - A combination of multiplex PCR with the single strand conformation polymorphism (SSCP) technique was employed to screen for point mutations in the human dystrophin gene. Co-amplification of 11 exons from genomic DNA of Duchenne and Becker muscular dystrophy (DMD/BMD) patients with no deletion or duplication was performed and the samples subjected to multiple SSCP analysis. We report the case of a nonsense mutation in a Duchenne patient identified by this approach. The mutation introduces a termination codon within exon 8 of the dystrophin gene. It is predicted to cause a very premature translational termination accounting for the severe phenotype observed. The patient inherited this mutation from his mother. In addition the analysis revealed 5 polymorphisms useful for internal control. PMID- 1307254 TI - Oligonucleotide probes for the analysis of specific repetitive DNA sequences by fluorescence in situ hybridization. AB - Five non-isotopically labeled oligonucleotides have been designed and synthesized to facilitate the analysis of specific human and murine repetitive DNA sequences by fluorescence in situ hybridization (FISH). Three of the oligonucleotides contain alphoid DNA sequences; one hybridizes to the centromeres of all human and mouse chromosomes except the Y, while the other two are specific for human chromosomes 2 and 12, respectively. The fourth oligomer, containing sequences from the spacer region of a human 5S rDNA repeat, was used to confirm the map location of a approximately 100 copy 5S rDNA tandem repeat locus. The fifth oligomer, specific to the Alu family of repeats, generates a sharp R-banding pattern on human metaphase chromosomes, suitable for FISH karyotyping. These probes permit highly specific chromosome enumeration and aneuploidy detection with hybridization times as short as 30 minutes. PMID- 1307255 TI - Mismatch PCR: a rapid method to screen for the Pro207-->Leu mutation in the lipoprotein lipase (LPL) gene. PMID- 1307256 TI - Dinucleotide repeat polymorphisms (D21S223 and D21S224) at 21q22.1. PMID- 1307257 TI - Dinucleotide repeat polymorphisms at the D11S439 and HBB loci. PMID- 1307258 TI - Dinucleotide repeat polymorphism at the D7S476 locus. PMID- 1307259 TI - Dinucleotide repeat polymorphism at the D9S147E locus. PMID- 1307260 TI - A chromosome 19 CA-dinucleotide repeat polymorphism. PMID- 1307261 TI - Dinucleotide repeat polymorphism between the human C4BPA and C4BPB gene loci (1q32). PMID- 1307262 TI - Dinucleotide repeat polymorphism at the D18S19 locus. PMID- 1307263 TI - Dinucleotide repeat polymorphism in the human thyroid hormone receptor alpha gene (THRA1) on chromosome 17. PMID- 1307264 TI - A new VNTR-type RFLP probe (ChdTC-15) on chromosome 12 (D12S65). PMID- 1307265 TI - Impotence. AB - The National Institutes of Health Consensus Development Conference on Impotence was convened to address (1) the prevalence and clinical, psychological, and social impact of erectile dysfunction; (2) the risk factors for erectile dysfunction and how they might be used in preventing its development; (3) the need for and appropriate diagnostic assessment and evaluation of patients with erectile dysfunction; (4) the efficacies and risks of behavioral, pharmacological, surgical, and other treatments for erectile dysfunction; (5) strategies for improving public and professional awareness and knowledge of erectile dysfunction; and (6) future directions for research in prevention, diagnosis, and management of erectile dysfunction. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel concluded that (1) the term "erectile dysfunction" should replace the term "impotence"; (2) the likelihood of erectile dysfunction increases with age but is not an inevitable consequence of aging; (3) embarrassment of patients and reluctance of both patients and health care providers to discuss sexual matters candidly contribute to underdiagnosis of erectile dysfunction; (4) many cases of erectile dysfunction can be successfully managed with appropriately selected therapy; (5) the diagnosis and treatment of erectile dysfunction must be specific and responsive to the individual patient's needs and that compliance as well as the desires and expectations of both the patient and partner are important considerations in selecting appropriate therapy; (6) education of health care providers and the public on aspects of human sexuality, sexual dysfunction, and availability of successful treatments is essential; and (7) erectile dysfunction is an important public health problem deserving of increased support for basic science investigation and applied research. PMID- 1307266 TI - [Malaria situation in the People's Republic of China in 1991. Advisory Committee on Parasitic Diseases]. AB - According to the case reporting system, there were 101,636 malaria cases in the nation (Taiwan not included) in 1991, the incidence being 8.875 per a hundred thousand, and 45 cases succumbed to the disease. In comparison with the data of 1990, the case number was reduced by 15,723 and the incidence, by 15.9%. In areas where there were no malaria cases occurred or the incidence was below 1/10000, the residents accounted for 88.1% of the whole population of the country, whereas incidence of 1-10/10000 was recorded in areas covering 10.0% of the total population, and only in areas with 1.9% population, the incidence exceeded 10/10000. In southern part, an increase of 8.61-54.35% in incidence was revealed in Guangdong, Guizhou, Yunnan and Guangxi provinces/autonomous region, which was accompanied by some focal outbreaks; the situation was primordially attributed to the frequency of population migration. In Hainan, Sichuan and Fujian provinces, the malaria incidence was reduced by 3.77-50.57%, however, increase in incidence was noted in individual places at district/city and county levels. In these 7 provinces/autonomous region, the subtotalled cases were 67,241, in a proportion of 66.2% of the total malaria cases of the nation. In the middle and eastern part, despite the flood severely affected many places in Anhui, Jiangsu, Hubei and Henan provinces in 1991, the implementation and intensification of malaria prophylaxis and treatment effectively resulted in an incidence decline by 9.44 41.28%, and no malaria epidemics had occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307267 TI - [Isolation and purification of Pneumocystis carinii cyst]. AB - Twenty Wistar rats were injected with cortisone acetate twice a week subcutaneously for 6-12 wks. By 7 weeks Pneumocystis carinii pneumonia was induced in rats successfully. The cysts of Pneumocystis carinii from infected lungs of cortisonized rats were identified by phase-contrast microscopy, Giemsa's stain, Chalvardjian's stain and Gomori's methenamine silver nitrate stain. The process of isolation and purification of Pneumocystis carinii from infected rat lungs included the following three test steps. First, the tissue was cut into small pieces and homogenized and filtered through #60, #100, #200-gauge wire mesh respectively. Secondly, the homogenate was digested with collagenase, the optimal concentration of collagenase being 0.2%. Thirdly, the discontinuous percoll density gradient centrifugation was used to separate P. carinii cysts. The majority of P carinii cysts were present in a density zone of approximately 1.033g/ml and were essentially free from host lung debris, the latter being removed due to their higher density, 1.040g/ml. PMID- 1307268 TI - [Diagnosis of toxoplasmosis by polymerase chain reaction]. AB - Based on the partial sequences of the specific DNA cloned fragment from T. gondii (ZS2 strain) a specific primer of the oligonucleotide for the Toxoplasma gondii DNA sequence has been designed and synthesized in our laboratory. The method of the DNA diagnosis for toxoplasmosis by polymerase chain reaction (PCR) has been established. A specific amplified band was shown in the PCR products from DNAs of T. gondii and seven manifold terata. The DNAs from the peripheral blood leukocytes of fifty normal individuals and seventy-five patients as infants with hepatitis syndrome and pregnant women with previous abnormal birth histories were diagnosed by PCR. Among the seventy-five diagnosed cases, ten were positive. The normal individuals all were negative. Using 32P-cloned T. gondii specific DNA fragment as probe and Southern blot assay, the results showed that the probe only hybridized to the specific amplified DNA bands, but did not hybridize to the amplified DNA products of negative cases. Our PCR method is a rapid, highly specific and sensitive one for detecting toxoplasmosis as compared with DNA probing, immunoassay and animal inoculation. PMID- 1307269 TI - [Studies on the establishment of malarial animal model of short-term relapse. I. Asynchronous growth of exoerythrocytic schizonts of Plasmodium cynomolgi]. AB - A monkey was infected with sporozoites of Plasmodium cynomolgi from Vietnam. Parasitemia was detected on the 8th day with a starting density of 17/100 white blood cells. 22 hours after that time, many EE schizonts appeared with an average density of 3.74 +/- 0.66 per mm3 hepatic tissue in liver biopsy specimens from the monkey. Most of the EE schizonts were immature and grew at an uneven rate, having an average diameter of 34.22 +/- 7.28 microns but some of them even remained 15.75 +/- 2.47 microns in diameter similar to the EE schizonts on the 6th day. The results showed that the EE schizonts of Plasmodium cynomologi were asynchronous in growth. The authors suggest that the release of merozoites from liver might be a successive process for many times, and not to be completed at a time. PMID- 1307270 TI - [Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitological observations]. AB - We compared the efficacy of a single dose of ivermectin with that of a standard course of deithylcarbamazine (DEC) for the control of microfilaremia in 60 patients with banrroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but transient clearance of microfilaremia was observed in both treatment groups. One year later, recurrent microfilaremia was present in 7 patients treated with ivermectin and in 5 treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremia. Side effects of either treatment were common but mild. Febrile reactions were more frequent in the ivermectin group: while localized reactions consistent with a flare up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis. PMID- 1307271 TI - [Characterization of a surface antigen of Plasmodium falciparum merozoite with monoclonal antibody]. AB - The monoclonal antibody (McAb) designated as C6 against erythrocytic stage of Plasmodium falciparum Fcc7801/HN showed significant growth inhibition of P. falciparum in vitro, having cross immunofluorescence reaction with P. falciparum Fcc-1/HN, Fcc7802/HN, Fcc8703/JS and P. berghei, P. cynomolgi. McAb C6 bound to the antigen distributed evenly over the entire surface of merozoites of P. falciparum, as demonstrated by immunoelectron microscopy. The McAb C6 also recognized a single protein of 71 kDa of P. falciparum by Western blotting. This antigen might be a candidate of malaria vaccine. PMID- 1307272 TI - [Preliminary study on the role of macrophage in processing and presenting antigens of Schistosoma japonicum]. AB - The horseradish peroxidase labeled affinity purified mice anti-UEA (Urea soluble egg antigen of Schistosoma japonicum) antibody was used in enzyme-linked immunoelectrotransfer blot (EITB) to monitor the changes after UEA being processed by M phi. The immune responsive peptides were detected in the culture supernatant and homogenate of M phi pulsed with UEA in vitro (M phi+). After processing by M phi the high molecular weight UEA was cleaved into low molecular weight peptides, as shown, by the reactive bands. They markedly differed from that native UEA or trypsin-digested UEA. The bands of M phi supernatant and homogenate showed similarity with certain quantitative differences. According to the result described above, we considered: 1. UEA could be processed into smaller pieces by M phi, the style of processing is cleavage. 2. The processed peptides might be released to extracellular environment. PMID- 1307273 TI - [Comparative study on antigenicity and immunogenicity of the 24-26 kDa antigen and the recombinant Sj26 antigen of Schistosoma japonicum]. AB - This paper reports on the comparison of the recombinant Sj26 (rSj26) antigen originated from the Philippine strain and 24-26 kDa antigen isolated and purified from Chinese mainland strain of S. japonicum for their antigenicity and immunogenicity. The results showed that there were obvious cross reactions between rSj26 and 24-26 kDa antigen when rSj26 antigen was tested against specific antibodies in sera from mice infected with the mainland strain of S. japonicum or 24-26 kDa antigen was tested against specific anti-rSj26 antibodies by ELISA, IFA and Western blotting etc. Both of 24-26 kDa and rSj26 antigen had weak cross reaction with SEA antigen. The worm reduction rate after challenging with mainland strain cercariae in mice immunized with rSj26 was 26-32%, similar to that in mice immunized with 24-26 kDa antigen. It is suggested that rSj26 antigen can induce certain level of specific protective immunity to protect the host against infection by Chinese strain of S. japonicum cercaciae. PMID- 1307274 TI - [Role of human and domestic animal reservoirs of schistosomiasis japonica in Dongting and Boyang Lake regions]. AB - In Dongting and Boyang Lake regions, the main reservoirs of schistosomiasis were farm cattle (mostly buffaloes), pigs and mobile nonnatives. However, the role of these reservoirs in different types of endemic areas were not the same in the transmission of schistosomiasis. In islet-beach type area, the main infectious sources were pigs and local residents. The proportion of IRC (Index of Real Contamination) of local residents and pigs to the total IRC was 30.9% and 39.9% respectively. In fork-beach type area having luxuriant grass and abundant aquatic products, there were a number of buffaloes and people from other places. The proportion of IRC of the nonnative buffaloes and mobile nonnatives made up 51.9% and 21.8% of the total IRC respectively, the main reservoirs being from other places. The embankment-beach type area had a vast snail-infected area and a large number of buffaloes from both local and other places as well as mobile nonnatives. The proportion of IRC of buffaloes and nonnatives made up 69.8% and 21.4% of the total IRC respectively, serving as the main reservoirs. As regard to season differences, the infected buffaloes were the main reservoirs during dry seasons, especially from March to May, whereas the mobile nonnatives including fishermen and boatmen were the main infectious sources during flood seasons from June to October. PMID- 1307275 TI - [Sensitivity in vitro of Plasmodium falciparum to chloroquine, pyronaridine, artesunate and piperaquine in south Yunnan]. AB - The sensitivity of P. falciparum to chloroquine, pyronaridine, artesunate and piperaquine (CQ, PD, AT, PQ) was assayed using in vitro microtechnique in south Yunnan in 1990. The resistance rates were 98.7% (75/76), 27.6% (16/58), 13.8% (9/65) and 97.7% (43/44) respectively, and ID50 were 125.0, 19.0, 4.7 and 243.3 nmol/L, respectively. The resistance rate against CQ showed no change as compared to the rates against CQ 5 and 9 years ago; but the ID50 was lower. CQ-resistant P. falciparum showed a marked cross-resistance to PQ, but not to PD and AT. AT resistant P. falciparum exhibited cross-resistance to the above-mentioned three drugs. PD-resistant P. falciparum showed no cross resistance to AT, but showed cross resistance to CQ and PQ. In comparison with chloroquine-coated plates, the plates coated with pyronaridine, artesunate or piperaquine gave similar results as the former, which were shown by the rise in schizont inhibition rates along with the rise in drug concentration. It indicates that pyronaridine-, artesunate , and piperaquine-coated plates can be used in the assay of sensitivity of P. falciparum to the three drugs. PMID- 1307276 TI - [Studies on the strain differences of Schistosoma japonicum in the mainland of China. X. Comparison of SDS-page protein patterns]. AB - The purpose of the present study was to investigate the SDS-PAGE separation of proteins of the 5 different isolates of Schistosoma japonicum from the mainland of China to determine their similarities and/or differences and to gain additional data which could give an added insight into the degree of relationship. Soluble proteins of freshly sonicated adult worm extract of the 5 different isolates (i.e., Anhui, Hubei, Guangxi, Sichuan and Yunnan) were compared by SDS-polyacrylamide gel electrophoresis. The results indicated that no marked difference could be observed among the isolates after gels were stained by Coomassie blue white both male and female worms of Guangxi isolate showed some definite differences in their protein profile, i.e., lack of 50-75 kDa band in male worms and a marked reduction in the quantity of > 110 and 30 kDa bands in female worms as shown by silver stain. PMID- 1307277 TI - [Effect of sodium artesunate on Plasmodium yoelii analysed by flow cytometry]. AB - The effect of sodium artesunate on Plasmodium yoelii-infected mouse erythrocytes was analysed by flow cytometry. The results showed that malarial DNA content in experimental group was obviously decreased 2-5 hours after the drug was administered, fluorescence distribution of malarial DNA almost disappeared within 24 hours after the administration. Thus we deem that sodium artesunate can inhibit the DNA synthesis in P. yoelii. PMID- 1307278 TI - [Observation on the effectiveness of repellent coating against mosquitoes]. AB - The present paper reports on the effectiveness of a repellent coating for the first time. The repellent coating was made by combining DETA (N,N-diethyl-meta toluamide) with slow-releasing reagent. With this coating employed in the laboratory against Aedes aegypti, the rate of blood-sucking was 3.9-9.5% and the rate of protection was 88.9-95.3% for 1-720 days. During 1-77 days' field trial, the RPI (Relative Population Index) was 0-8.98% in the day-time and 0.74-17.15 during the night-time against Anopheles sinensis, Culex pipiens pallens and Culex tritaeniorhynchus. It is concluded that the repellent coating is effective against mosquitoes, safe and prolongs the protection time following exposure to mosquitoes. PMID- 1307279 TI - [Comparison of mosquito larvicidal efficacy between microbial encapsulated BTI (EBTI) and standard BTI (SBTI)]. AB - A comparative study was conducted on the efficacy of mosquito larvicides EBTI and SBTI. The results showed that: 1. The residual efficacy of EBTI was remarkably higher than that of SBTI at 0.007-0.002ppm BTI concentration (P < 0.01), the mosquito larvae mortality of EBTI remained 100% until the 4th week; in contrast, the mosquito larva mortality of SBTI gradually and obviously declined from the 2nd to 4th week after treatment (x2 = 8.17-24.08), and reached 0 at the 4th week. 2. The lowest BTI concentration of EBTI at which a high efficacy persisted for 4 weeks was 0.007ppm BTI, the mosquito larva mortality remaining 100%. PMID- 1307280 TI - [Toxoplasmic retinochoroiditis]. AB - Retinochoroiditis is a frequent ocular lesion in toxoplasmosis. It may be severe, and even lead to blindness. Sixteen cases of toxoplasmic retinochoroiditis verified through IFA were presented in this paper. Among these cases, 1 was of the multifocal type, its appearance being similar to that of the Coats disease; while the other 15 were of the focal type resembling to the central exudative retinitis (Rieger disease) or retinochoroidal scar. Serological finding of all the cases showed a positive IFA titer of > 1:80. A combination of pyrimethamine and sulfadiazine as well as spiramycin in addition to dexamethasone had been administered and proved effective. Since toxoplasmosis mostly occurs as latent and examination of the eye cannot differentiate from other causes of retinochoroiditis, so such clinical report of toxoplasmic retinochoroiditis was rare with particular reference in our country. The authors claimed that any individual presenting with retinochoroiditis suspected of toxoplasmosis should be subjected to serologic antibody test for establishing diagnosis. PMID- 1307281 TI - [Observation on metacercariae of Paragonimus westermani by transmission electron microscopy]. AB - The ultrastructure of metacercariae of Paragonimus westermani was observed by transmission electron microscopy. The worm is composed of integument, parenchyma, gut and excretory sac. The integument consists of tegument, muscular layer and tegumental cell. The tegument, a syncytium, includes tegumental membrane, tegumental cytoplasm, and basal plasma membrane. On the surface of the tegument, many finger-like processes with branches and spines can be readily identified. The spines projecting beyond the surface of the tegument are completely enclosed within the outer tegument membrane and the basal plasma membrane; in the transverse section, the spine shows a crystalline lattice structure. The tegumental cytoplasm consists of an electron dense granular matrix, in which two types of inclusion bodies, spherical and rod-like bodies may be recognised, both of them comprise a unit membrane and dense granular contents, the rod-like bodies are arranged along the edge of the spines. The tegument nuclei are located not within the surface syncytium but within sunken tegumental cells situated beneath the muscle layer, the tegumental cells contain a few cell organelles, and the two types of characteristic tegument inclusion bodies. The cells are joined to the tegument by one or more long, tortuous cytoplasmic tubules, responsible for the synthesis of the tegumental inclusion bodies, and that these inclusion bodies are translocated into the tegument by the cytoplasmic tubules. It suggests that the tegument of metacercaria is the main absorptive site of nutrients. PMID- 1307282 TI - [Scanning electron microscopic observation on Demodex brevis]. AB - This paper presents the first description of the morphology of Demodex brevis examined by scanning electron microscopy. The authors found that D. brevis can be distinguished from D. folliculorum by the characteristic features of the following structures: the flat gnathosoma, the humplike podosoma and the absence of transverse striation on its anterior dorsal surface, the supracoxal spines, the hypostome, the oral opening, the pedipalpal claws and the claws on legs, and the annuli of the terminal part of the opisthosoma. The morphology of the above structures observed are briefly compared with those of D. folliculorum. PMID- 1307283 TI - [Experimental study on detection of serum antibodies by immunoenzyme staining using adult Angiostrongylus cantonensis frozen section]. AB - This paper reported on the results of detection of serum antibodies in rats with Angiostrongylus cantonensis infection by immunoenzyme staining of adult frozen section. The positive rates of serum antibodies in rats 2 and 4 weeks after infection were 80% and 93.3%, respectively. The result of healthy control rats was negative. PMID- 1307284 TI - USAN Council. List No. 340. New names. Molgramostim. PMID- 1307285 TI - USAN Council. List No. 340. New names. Sargramostim. PMID- 1307286 TI - [Transabdominal termino-esophago-proximal gastrectomy for portal hypertension. An analysis of 61 cases]. AB - The results of transabdominal termino-esophago-proximal gastrectomy in 61 patients with portal hypertension were presented. The patients were followed up for 2 to 7.5 years. Two patients died from the surgery. There was no esophageal varix rebleeding during the follow-up period. We conclude that it is a good method for controlling bleeding varices. PMID- 1307287 TI - [Immune complex in the wall of the gallbladder in patients with cholelithiasis: deposition and its pathological significance]. AB - The gallbladder specimens from 53 patients with cholelithiasis were studied by immunohistochemical method. Deposition of immune complex (IC) was observed on the mucosal and glandular epithelium in 84% of patients with gallstones and 47% of patients with choledocholithiasis. IgG and C3 were the most frequent complement component demonstrated at the site of IC deposition, but Clq, factor B and C4 were also present in many cases, suggesting the local complement activation. We conclude that IC may play a pathogenetic role in the injury of the mucosa and tissue of gallbladder in patients with cholelithiasis. PMID- 1307288 TI - [Primary retroperitoneal tumors]. AB - Two hundred and one patients with primary retroperitoneal tumors underwent surgery from 1957 to 1988. The tumors were found malignant in 113 patients (56%) and benign in 88 (44%). Abdominal mass and/or pain was the most common symptom (88%), with palpable abdominal mass in 91% of the patients. Complete resection was performed in 81% of the patients with benign tumors and 51% with malignant ones. Fourteen patients (24%) with malignant tumors were subjected to the excision of adjacent organs for the complete resection. The 5- and 10-years survival rates of the patients with benign tumors were 96% and 95% respectively. In patients with malignant tumors, the 5- and 10-year survival rates were 56% and 30% respectively for those undergoing complete resection, compared to 8% and 8% respectively for those undergoing partial resection or biopsy (P < 0.001). Partial resection with adjuvant radiotherapy or chemotherapy may be beneficial to some of the patients with malignant tumors. Reoperation should always be attempted in patients suffering from recurrence. PMID- 1307289 TI - [High risk factors in the prognosis of acute necrotizing pancreatitis]. AB - In this study, Ranson's risk factors were evaluated on 36 cases of acute necrotizing pancreatitis. It was found that all 13 cases with more than 7 factors each died, the mortality rate was 100%, and 2 of 5 cases with 5-7 factors each succumbed with the mortality rate of 40%. The remaining 14 cases, all of them with less than 3 factors each, survived the stormy attacks. The authors believe that Ranson's risk factors are reliable in predicting the prognosis of acute necrotizing pancreatitis. PMID- 1307290 TI - [The correlation between urine urea nitrogen and total urine nitrogen output in perioperative patients]. AB - Daily urine urea nitrogen (UUN) and total urine nitrogen output (TUNO) concentrations were measured in 19 patients undergoing G-I surgery during the perioperative period of 114 days. The results showed that there was a strong correlation between UUN and TUNO in statistic regression analysis. A formula is worked out TUNO = UUN + 0.7 which is of great value in estimating the nitrogen balance of TPN patients. PMID- 1307291 TI - [Veno-valvulectomy and primary in situ arteriolization of the great saphenous vein for the treatment of ischemic lower limbs]. AB - After the study of the valvular distribution of 18 cadaveric great saphenous veins, we performed microsurgically great saphenous veno-valvulectomy and primary in situ veno-arteriolization for 18 severely ischemic limbs of 17 patients of these patients, 14 had thromboangiitis obliterans, and 3 arteriosclerosis. 16 patients were followed up for 14 to 32 months after operations. The results were excellent. The procedure is a good alternative for the treatment of extensive arterial occlusive disease of the lower limbs. PMID- 1307292 TI - [Effects on the normalization of amino acids in metabolic support for trauma surgical patients]. AB - Both serum and muscle intracellular amino acids pattern are changed after trauma. The formulation of amino acid solutions is important for the balance of the patient's serum or intracellular amino acids. In 45 gastric cancer patients after total gastrectomy, the efficacy of individualizal amino acid solution (IDAA) was compared with that of other two balance amino acid solutions. The result showed that metabolic support with IDAA could decrease the muscle intracellular phenylalanine level and increase the levels of free neoglycogenic amino acids, arginine and ornithine both in serum and muscle cells. It is beneficial to the early recovery from trauma and normalization of serum or muscle amino acids pattern. PMID- 1307293 TI - [Embolization of drainage veins used in sclerotherapy of hemangiomas]. AB - To improve the result of sclerotherapy for hemangiomas, the drainage veins of hemangiomas were embolized by injecting 95% alcohol into the hemangioma cavities. Alcohol injected into the cavity had to drain away through the vein of hemangioma and result in damage of the endothelial cells, and thrombosis on the venous wall, then the drainage vein is embolized. With the result of embolization of the drainage vein, the sclerosant solution injected into the hemangioma cavity cannot flow off any more. The sclerosant solution got much time to bring drug action into play, so the curative effect was raised. 30 patients including 24 cavernous hemangiomas and 6 mixed hemangiomas were treated with this method. 15 cases were cured, 11 cases were effective and 4 cases were ineffective. The effective rate was 86.7%. PMID- 1307294 TI - [Operation for discrete subvalvular aortic stenosis]. AB - 33 patients with discrete subvalvular aortic stenosis, membranous in 14 cases, fibromuscular rige in 16 and tunnel in 3 were treated surgically in the past ten years. This spectrum of abnormalities can be differentiated by echocardiography and angiocardiography. Our policy is to excise the membrane or fibromuscular rige. When the outflow tract has remain narrow owing to concentric thickening of that portion of the septum and free wall proximal to aortic annulus, a septal myomectomy is indicated. Because the operation of subaortic stenosis is safe and effective, once the diagnosis is established, operation is a reasonable surgical treatment alternative. Operative mortality rate was 6%. Follow-up results of all survivors are satisfactory. PMID- 1307295 TI - [Thoracoplasty in scoliosis]. AB - Since 1978, 108 cases of scoliosis with severe thoracic deformity have received thoracoplasty. Most of them were operated at the same time for correction of scoliosis. The resected ribs were served as bone graft for posterial spinal fusion. The rib prominence was reduced 2.5-6.9 cm after operation, and the costectomy also found to be beneficial to the correction of lateral curvature and axial rotation of the spine. The thoracoplasty showed no affect upon the pulmonary function. In this paper, three kinds of thoracoplasty and their indications are discussed and compared. PMID- 1307296 TI - [Closed rupture of the cervical trachea]. AB - Two patients with closed rupture of the cervical trachea secondary to blunt trauma, one secondary to neck injury and the other secondary to thoracic injury, were analysed with those reported else where (58). Signs and symptoms included subcutaneous emphysema, respiratory distress, hoarseness/dysphonia, dysphagia, hemoptysis and so on. We conclude that: (1) the diagnosis of blunt trauma of the cervical trachea requires a high index of suspicion, since this injury can easily be overlooked; (2) tracheostomy is the best means of airway control; (3) good long-term airway quality is best obtained by immediate repair of injuries. PMID- 1307297 TI - [Experience in repairing fistula of bronchus by Eleosor's method]. AB - The repairing treatment of 10 cases of the fistula of bronchus stump by us/ng Eleosor method was reported in this article. All the 10 cases were cured once and no one died of operation. The author have introduced the way of operation and compared it with the other methods of treating such a disease at present. This operation method have the characteristics of collapsing the thorax on the troubled side thoroughly, filling the fistula with large fresh muscles which have very good blood circulation and suturing the wound by the nearest sleeve way etc. The curative effects of such treatment is superior to other way of operation. PMID- 1307298 TI - [Postoperative cardiac intensive care for patients with thoracic cancer: analysis of 430 cases]. AB - 430 patients with thoracic cancer were given intensive care after major thoracic surgery. Of those 188 (43.72%) developed cardiac complication during their stay in ICU and 2 (0.46%) died. The results indicated that postoperative cardiac complications were closely related to the patients age, preoperative concomitant cardiovascular diseases, duration of operation, hypoxemia, hypercapnia, and surgical complications. Postoperative cardiac intensive care could reduce the mortality rate. PMID- 1307299 TI - [Diagnosis and treatment of primary aldosteronism]. AB - Twenty-eight patients with primary aldosteronism were treated from 1974 to 1990. The serum potassium concentration was higher than normal level in all patients with the exception of one whose serum potassium concentration was normal. All of 14 tested patients had low renin values. The plasma aldosterone concentration was higher than standard value in all of 5 patients, and the A/PRA ratio was more than 400. Spironolactone administered preoperatively could not only normalize serum potassium concentration level and blood pressure, but also predict postoperative prognosis of hypertension. Only 37.5% of adenomas were detected by retroperitoneal pneumography with tomography in the early period. 80.0% of adenomas were found by B-ultrasonography, and 92.8% by CT after 1982. The operation was done through abdominal incision because of indefinite localization of adenoma before 1982, and the operation was performed through lumbar incision because of definite localization of adenoma after 1982. PMID- 1307300 TI - [Pericatheter urethrography and its use in post interlocking sound urethroplasty]. AB - 21 cases of posterior urethral rupture due to pelvic fracture were treated by acute interlocking sound urethroplasty since 1982. Postoperative pericatheter urethrography was carried out to observe the recover of urethral rupture. The results showed that the time for recover of ruptured urethra varied from 4 to 13 weeks. 71% of all cases required more than 8 weeks for recovery. The patients were followed up from 1 to 9 years, and 86% of them showed satisfactory results. It is believed that pericatheter urethrography not only provides an objective proof for the recovery of ruptured urethra but also can be used as a reliable basis for the removal of stenting catheter. PMID- 1307301 TI - [Sensitivity of Staph aureus and Ps. aeruginosa and clinical application of antibiotics in patients with burn septicemia]. AB - The sensitivity of 245 strains of Staph. aureus and 171 strains of Ps. aeruginosa to antibiotics was tested in patients with burn septicemia. The results indicated that both the bacteria were resistant to the widely used antibiotics. The causes for producing the resistance to drugs were analyzed. We consider that "circular therapy" of antibiotics, alternatively stopping and reusing some antibiotics according to the variation in the bacterial resistance to drugs, should be a valuable method for preventing the resistance to drugs. PMID- 1307303 TI - [Gamma knife and its clinical application]. PMID- 1307302 TI - [The research on etiology and physiopathology of abdominal aortic aneurysm]. PMID- 1307304 TI - [The normal gait and clinical application of gait analysis]. PMID- 1307306 TI - [The mineral content in adult radius and ulna in southwestern area of Guang-xi]. AB - We investigate the BMD of ulna and radius of 2690 persons in southwestern areas of Guang-xi. The results show that the bone mineral content in male is higher than that in female and it is higher in middle-aged person than in the elderly. It is at 32-33 years old that the BMD reaches the peak, then decreases after 35 years old with 5-7 percent and/10 percent loss of the bone mass in male and female per 10 years, respectively. The losing rate of bone mass in female after 50 years old is faster than that in male. In addition, we compared the BMD in workers of different professions at the same age, and found that the heavier the labour intensity, the higher the bone mineral content and the BMD is higher in workers doing outdoor works. The bone mineral content in miners who work in the mine for a long time is lowered. This presentenship that there is a close relationship between the bone mineral content and age, sex, sunshine exposure and intensity of labour. PMID- 1307305 TI - [Postmenopausal osteoporosis and treatment with sex hormones]. AB - An animal model of postmenopausal osteoporosis was established and the animals were treated with sex hormones in the experiment. From a group of fifty female Wistar rats, forty were castrated and ten were subjected to sham operation served as controls. After fourteen weeks, ten rats each from the castrated (the Model group) and control rats were killed. Through bone histomorphometry and bone mineral analysis it was sure that a good model of postmenopausal osteoporosis was established with a high bone turnover rate at the tissue level. The bone loss occurred mainly at the trabecular surface through decreased osteoblastic activity, resulting in a negative balance of the bone metabolitic unite. Of the remaining thirty castrated rats, ten were treated beginning from the 15th week for eight weeks with oestrogen, ten with progesterogen, and ten without treatment served as positive controls. The result showed that stilbestrol at 0.2 mg/day could maintain bone mass, and provera alone at 0.8 mg/day had the similar effect as oestrogen. PMID- 1307307 TI - [Electrical stimulation in the treatment of osteoporosis in sciatic denervated rat tibia]. AB - Osteoporosis in the sciatic-denervated rat tibia was reversed with a capacitively coupled electrical field. In the reversal of a previously established osteoporosis, a statistically significant enhancement of wet weight, dry weight, ashed weight, ultimate strength, cortical area, cortical thickness and a concomitant decrease in cortical porosity occurred in the stimulated, denervated tibiae of the experimental animals compared with the nonstimulated, denervated tibiae of the control animals. A 60 Hz symmetrical sinewave signal was effective in reversing osteoporosis at 10 V peak to peak. Reversal of a well-established osteoporosis in laboratory animals has not been reported previously. PMID- 1307308 TI - [The changes in bone mineral content in experimental limb lengthening]. AB - The results of bone mineral content measurement in experimental limb lengthening are reported. The results demonstrated that in the restoring process, both the strength and the stiffness of the lengthened bone are positively correlated to the relative bone mineral content with coefficients of correlation 0.59 (P < 0.001) and 0.85 (P < 0.001) respectively. Analyses of curve fitting showed that the strength is directly proportional to the 1.7479 th power of bone mineral content and the stiffness to its 2.05842 th power Hence, the authors consider that bone mineral content measurement could be used as a noninvasive index for monitoring the changes of bone strength and stiffness during recovering process of bone lengthening. PMID- 1307309 TI - [Comparison of the stress distribution with bone density in the spine]. AB - The results of study on stress distribution of the lumbar spine analyzed with a mechanical model of the lumbar motion segment constructed by a three-dimensional finite element method, and the comparison of resulting values with the corresponding bone density represented by the attenuation value of CT were reported. The results indicated that the stress levels in various parts of the lumbar spine were closely related to the CT values. The authors conclude that the mechanical stress is an important factor in maintaining the dynamic balance of bone growth. PMID- 1307310 TI - [Quantitative computed tomography in the diagnosis of osteoporosis]. PMID- 1307311 TI - [Culture and characterization of normal human hepatocytes]. AB - Small pieces of normal liver tissues were obtained from patients with gallstones undergoing cholecystectomy, and hepatocytes were isolated from these tissues. They were cultured in a medium of DFH containing several growth factors and hormones, successively for more than two years over 60 passages. They showed doubling time about 25 hours, peak mitotic index near 4% and heteroploid karyotype. They kept secreting some enzymes and albumin, that are usually produced by normal liver tissue. In contrast with hepatoma cells, the cultured normal hepatocytes failed to form xenograft tumor in nude mice and their proliferation was depended upon exogenous growth-factors in vitro. The cultured hepatocytes can be used as a cell model for study of carcinogenic process and stored as a cell-pool for clinical cell transplantation in the coming years. PMID- 1307312 TI - [Carcinoid of the digestive tract. An analysis of 36 cases]. AB - 36 cases of carcinoid of the digestive tract were presented. The malignancy of the carcinoid was established solely by the presence of local infiltration and remote metastasis irrespective of the size of the original tumor three of 10 cases of the tumor less than 2 cm in diameter had metastasis although smaller tumors were usually benign. Immuno-histochemistry study in 15 cases showed 1-4 kinds of different polypeptides in each case. Three of 8 cases of malignant carcinoid syndrome had normal blood level of 5-HT and 5-HIAA, suggesting other polypeptides as the cause of the syndrome. The absence of hepatic metastasis in 4 of the 8 cases favors the hypothesis that polypeptides may get access to the general circulation by such as retroperitoneal pathways. PMID- 1307313 TI - [Surgical treatment of esophageal stricture after chemical burn]. AB - 26 patients with esophageal stricture caused by chemical burn were treated from Nov. 1972 to Nov. 1990. No operative death occurred. Follow-up showed good therapeutic effects 92.3% of the patients. We believe that surgical treatment using colonic interposition as the main procedure may bring about satisfactory results. The indications for dilatation of esophageal stricture, preoperative treatment and selection of reconstruction of the esophagus are discussed. PMID- 1307314 TI - [Neurovascular decompression for hemifacial spasm]. AB - Thirty-six cases of hemifacial spasm were treated by neurovascular decompression. Via transposterior cranial fossa approach, a small incision was made behind the ear. After careful dissection, a piece of teflon was placed between the vessel and initial segment of the facial nerve root and fixed with silver clip after wrapping of the nerve root. The cases were free from tic immediately after operation. Follow-up of 34 cases for 1 month to 3.5 years showed no recurrence and less and mild operative complications. In this series physiological function of the facial nerve was kept well and there was no mortality. This operation is regarded as the first choice in the treatment of hemifacial spasm. PMID- 1307315 TI - [Therapeutic results after resection of asymptomatic lung cancer]. AB - This article reported a group of 43 cases of lung cancer who had no symptoms before resection, and were detected by mass screening or routine physical examination. They accounted for 15.2% of 282 cases undergoing lung cancer resection during the periods from January, 1977 to June, 1990 in our hospital. Pathologic study of the resected specimens showed that there were 32 cases of Stage I lung cancer (74.4%). Among them 15 cases were of early stage (T1N0M0) which accounted for 5.3% of 282 cases. 5-years survival rate of this subgroup was 81.8%. About one fourth of asymptomatic lung cancer belonged to middle or late stage. PMID- 1307316 TI - [Selective control of blood supply to part of thoracic wall before resecting intrathoracic lesions with adhesions rich in systemic bypass]. AB - Five patients with intrathoracic lesions with dense adhesions containing rich systemic-pulmonary were treated with selective control of blood supply to part of thoracic wall. Four of five patients were followed up for more than five years and were found excellent in health. Operative method and high lights were described. During the operation, this method for the prevention or control of severe bleeding was proved to be useful in above mentioned cases. PMID- 1307317 TI - [Emergency lung resection in patients with massive hemoptysis]. AB - Emergency lung resection was done in 32 patients with massive hemoptysis. The morbidity and mortality rates were 18.75% and 6.25% respectively. Problems about how to find the focus of hemoptysis, when to perform the operation, how to select anaesthesia, operative techniques and limits of lung resection were discussed. PMID- 1307318 TI - [Closure treatment of finger-tip injury with chimehers]. AB - The result of closure treatment of 98 finger-tip injuries in 79 patients with Chimehers were reported. Of these injuries, 91 (93.8%) were crush injury. Among these patients, 54 were injured in industrial accidents and 46 patients (85%) resumed their original work within one month after healing of wound. Typing was done for these 98 finger-tip injuries, and their prognosis was evaluated in this paper. Besides, the basic principles for the closure treatment with Chimeherb were also presented. PMID- 1307320 TI - [Adherent skin grafting: experiment and clinical application]. AB - Adherent skin grafting, using a biological binder abstracted from different animal tissues, was done successfully in 24 rabbits. The grafting was also performed in 26 patients; the results were satisfactory in all but 2 with disseminative dry necrosis of the grafted skin caused by excessive binder. We consider that this method is simple and of clinical value. PMID- 1307319 TI - [Bile acid pool in the formation of pigment stone: an experimental study]. AB - A method with isotopic 3H-CDCA was established to determine bile acid pool. Sixty male guinea pigs were divided randomly into two groups; 20 guinea pigs fed with standard chow served as control, and 40 with 10% low protein lithogenic chow were subdivided into 4 groups executed on 10,20,30 and 40 days (In the last subgroup, vitamin C was added to the chow), respectively. The bile acid pool of lithogenic animals decreased on the 10th days and significantly decreased on the 20th, 30th, 40th day (P < 0.01) when compared with controls in the same periods. The incidence of pigment gallstone was 90% on the 20th day, 100% on the 30th day, 40% on the 40th day in lithogenic animals. The pool size decreased slightly on the 40th day in lithogenic animals which were fed with supplement of Vitamin C. A significant positive correlation was noted between gallbladder volume and bile acid pool size (r = 0.842) in the 30th day lithogenic animals. We postulate that the decreased bile acid pool size occurs before the development of pigment gallstone and it may be an important factor in promoting the formation of gallstone. PMID- 1307321 TI - [Microcirculation in unphysiological flaps at early stage after operation: an experimental study]. AB - Microcirculation and blood perfusion in unphysiological flaps were observed with rabbit ear microcirculation chamber. The microcirculation of the venous flap in two days after operation was reestablished mainly by diversion of blood flow through the "to and fro" movement of venous blood. Arteriovenous anastomoses were gradually opened, resulting in the microcirculation to restore normal perfusion, venous blood through the anastomoses into arteriole then to capillaries. The microcirculation of arterialized venous flaps was almost the same as that of the venous flaps. In two days after operation, the diversion of blood flow perfused the capillaries under high pressure, so that the flow velocity and rate were much faster and larger than those of the venous flaps. The microcirculation of venouslized arterial flap, nourished by venous blood through the arterial system, was the same as that of the physiological flap. But the capillaries were perfused venous blood flow, and the blood flow velocity and rate were much slower and smaller than those of the physiological flap. PMID- 1307322 TI - [Reconstruction of first web space of hand: follow-up analysis of 40 cases]. AB - The follow-up outcome of 40 cases after reconstruction of the first web space of hand was reported. Of them, the hand function was improved in 31 cases, not improved in 6 cases, and worsened in 3 cases. The authors thought that the pedicled ilio-inguinal axial flap for treatment of first web space defect is one of the reconstructive methods for choice in spite of its bulky appearance. Though the operative method of the dorsal local skin flap of hand is simple, it may interfere with the flexion of MP joint of the index finger and the reconstructed first web space is very deep and not plumpy. The author proposed that the extent of the reconstructed first web space should depend upon the patient's occupation, and that the function of internal muscles of the hand and of the flexion and extension muscles of thumb should be taken into consideration because too large a first web space may interfere with the function of opposing finger. PMID- 1307323 TI - [Treatment of chronic mallet finger with tendon flap graft. Report of 16 cases]. AB - A series of 16 cases of chronic mallet finger deformity repaired with tendon flap from palmaris longus tendon or lateral band of extensor tendons is reported. Follow-up ranged from 1 to 4 years, the deformity has been corrected and pain disappeared in all cases. The active extention of DIP joints are 0 degrees in 12 cases and 5 degrees-15 degrees hyperextention in 4 cases. The active flexion of DIP joints are normal (65 degrees-80 degrees) in 11 cases, has 5 degrees-15 degrees flexion lag in 5 cases. The PIP and MP are normal in all cases. The anatomic basis of this procedure is narrated. The restoration of the anatomic continuity of the terminal extensor tendon reestablishes the coordinative effect between the long extensor tendon, intrinsic lateral band and oblique retinacular ligament and thus brings good long term result. PMID- 1307324 TI - [Surgical results of various injuries related to central slip in extensor tendon of the hand]. AB - In this article the results of surgical repair in 41 cases with different degrees of the central tendon band injuries of hand were reported and the results were compared for different kinds of operation. In this series all patients with degree I injury (3 cases) achieved excellent result by direct repairing disrupted tendons. 25 cases with degree II injury were repaired using three different procedures, among which the method of splitting lateral bands with cross suture yielded better result. However, only 7 patients (47%) reached excellent and good result, The reason for that is due to attention paid insufficiently to key problems during operation. For degree III injury only 5 cases out of 13 attained excellent and good result by transplantation of free tendons. The main cause for that failure is that the operator misplaced the crossing point of the tendons. PMID- 1307325 TI - [An experimental study of the treatment of root avulsion of brachial plexus using contralateral C7 nerve neurotization (nerve transfer)]. AB - This study compared the functional results of contralateral C7 root neurotization with homolateral phrenic nerve transfer for repairing root avulsion of brachial plexus in rats. It was found that in the C7 nerve root group all the parameters of evoked muscle potential amplitude (EMPA), regenerating axon count, biceps weight and muscle fibre area, and muscular maximal tetanus tension were statistically superior (P < 0.05-0.01) to those in the phrenic nerve group; while there were no significant differences between these two groups in motor nerve latency regenerating axon area and persisting time of muscular maximal tetanus tension (P > 0.05). The reasons why C7 root neurotization is superior to phrenic nerve transfer were also discussed. PMID- 1307326 TI - [Congenital perforation of the triangular fibrocartilage of the wrist]. AB - The authors dissected 136 wrist joints from fetus and infant fresh cadavers. The perforation rates of the triangular fibrocartilage of the wrist in these two groups were found to be 18.8% and 25%, respectively. The authors believe that, besides traumatic, inflammatory and degenerative causes, some perforations are congenital in origin. They are not found to be correlated with either sex or side of wrists (P > 0.05). PMID- 1307327 TI - [A microcirculation observation of the venous flaps]. AB - This article presented the observation results of microcirculation of 84 island venous flaps performed on the ears of 42 rabbits. The survival rates of 5 groups divided by differently handling the vessel pedical of the flaps were: 1. maintaining artery and venous 90.36%. 2. maintaining distal and proximal venous 86.29%. 3. only maintaining proximal venous 75.71%. 4. only maintaining distal venous 28.75%. 5. ligating all vessels O(P < 0.01). The results of blood flow examined by laser Doppler and the number of micrangium counted by microcirculation microscope were decreasing upon the sequence of the above groups (P < 0.05). We found that there were exact microcirculation in the venous flaps of group 2, 3, 4, but the blood flow in these groups, especially the group 4, were slower than the group 1. PMID- 1307328 TI - [Clinical evaluation of blood supply of the hand]. AB - The blood supply of 39 apparently normal hands was examined by the use of the Allen test and a Doppler Ultrasonic Blood Flow Detector. The ultrasonic examination appears to be more sensitive to the change of blood supply to the hand than the Allen test and to have higher degree of accuracy. The Allen test seems to provide some useful information, but it is a relatively crude test. The ultrasonic examination should become one of the routine examinations of patients who are likely to undergo procedures which may interfere with the normal circulation of the hand. PMID- 1307329 TI - [Percutaneous transluminal angioplasty of subclavian arteries]. AB - 12 cases of subclavian arterial stenosis or obstruction were treated with percutaneous transluminal angioplasty (PTA). Atherosclerosis was considered as the cause of the arterial lesion in 7 cases. In 6 of them the lesion was located near the orifice of the subclavian artery. The lesion was 10.8 +/- 5.4 mm in length and 1.67 +/- 0.8 mm in diameter. After PTA the lumen was 6.58 +/- 1.11 mm in diameter. The clinical result was satisfactory. Arteries was found in 5 cases. Most of them had long segment obstructed lesion (46 +/- 36.6 mm in length, and 0.5 +/- 0.5 mm in diameter). The result of PTA was not satisfactory. The technique of PTA has been discussed. PMID- 1307330 TI - [Acute purulent pericarditis: clinical experience with primary pericardiectomy plus continuous pericardium lavage]. AB - 106 patients with acute purulent pericarditis were treated surgically with three different methods without operative mortality. The pericardiectomy plus continuous pericardial lavage was more effective than pericardiectomy without irrigation or simple pericardial drainage in several aspects, such as recovery of body temperature, elimination of infectious-toxic symptoms and cutting short hospitalization days. Besides, cardiac tamponade or late constriction of the pericardium could be avoided. PMID- 1307331 TI - [Lung hamartoma: a report of 30 cases and review of 477 cases]. AB - 507 cases of lung hamartoma (30 cases reported and 477 reviewed) were analysed. 467 cases of them were of intrapulmonary type, 30 were endobronchial, 8 were multiple and 2 were diffuse. 505 were benign and 2 malignant. The male to female ratio was 1.74:1. The age span was from infant to 67 years with a mean of 41.4 years. 44.3% of the lesions showed no symptoms. The frequently seen symptoms were cough and chest pain. X-ray findings of the intrapulmonary type were characterized by sharply outlined round or oval mass (87.9%), with diameters 3.0 cm (62.1%), lobulation (33.5%), calcification (23.6%). These tumors grew slowly. The average doubling time for 16 cases was 4.2 years. The diagnosis was confirmed in only 18% cases preoperatively. The other cases were misdiagnosed as lung cancer, tuberculoma, metastatic tumors of the lung, etc. The etiological causes, classification, diagnosis, differential diagnosis and treatment of the tumors were discussed. PMID- 1307332 TI - [The microsurgery of the tumor involving Meckel's cave and nearby area]. AB - A retrospective review of 12 cases of tumor involving Mackel's cave and nearby area seen at the Tongji hospital in a 20-year period. All of the cases may be divided to three clearly defined clinical groups: (1) Patients with typical trigeminal neuralgia. The tumor usually involve the ganglion. After removal the mass the prognosis were excellent. (2) Schwannoma or neurofibrosarcoma embedded in the semilunar ganglion with a history of atypical face pain without neurological deficit. After operation the pain relief was not as good as the group 1. (3) Patients with the history of face dysethesias and pain, tumors usually involving the middle fossa of cranial base with multiple cranial nerve deficit. These patients had variable mass lesions and after removed tumor the prognosis was not as good as in group 1 and group 2. The anatomy of Meckel's cave and surgical technique in treating these tumors were discussed also. PMID- 1307333 TI - [Surgical treatment of left ventricular right atrial fistula (II-type): report of 12 cases]. AB - 12 cases of left ventricular right atrial fistula (II-type) were identified and repaired by open heart surgery. Our date showed that defects of the septal leaflet of tricuspital valve can be divided into three groups: multiple-opening, single-opening and split defects. When there were VSD and fistula at the same position, the VSD was not repaired completely if the opening of tricuspital septal leaflet was mistaken as the VSD itself. It is important to expose the edge of the VSD completely by cutting tricuspital septal leaflet when repairing the VSD. The cutting septal leaflet can be sutured after closure of the VSD. PMID- 1307334 TI - [Preoperative CT scan for esophageal tumor]. AB - Thoracic CT scans were performed preoperatively in 19 patients with carcinoma of the esophagus and one patient with esophageal leiomyoma. CT findings were compared with surgical and pathological findings before and after operation. CT was shown to be inaccurate in the preoperative assessment of the involvement of esophageal carcinoma and of little value in judging potential resectability (69%). Its accuracy was low in staging the tumor, usually understaging (37.5% staging II) or overstaging tumor (45.4% staging III), without information about suitable treatment of esophageal cancer. With low accuracy in visualizing lymph nodes of the mediastinum and periesophagus (30%), it is not helpful in distinguishing benign from malignant tumor of the esophagus. PMID- 1307335 TI - [Need for more emphasis on fungal infection in burns]. AB - We have made quantitative bacterial and fungal culture for 148 biopsy specimens from burn patients. Further confirmation was made by frozen section with PAS stain in 82 of the specimens. It was discovered that the fungal infections in these burn patients were characterized by early onset with multiple organisms. It was also found that the incidence of fungal infections was higher in severe burns. Two rare cases of fungal infection were discovered, one of them was infected by Geotrichum SP, and the patient died; the other an infection by Homodendrum SP on the face, and the finally recovered. PMID- 1307336 TI - [Traumatic external gastrointestinal fistula: report of 77 cases]. AB - Seventy-seven patients developed gastroenteric fistula as a complication of abdominal trauma, including small bowl fistula (25), duodenal fistula (17), colonic fistula (16), pancreatic fistula (3), gastric fistula (2), and multiple fistula (14). These patients accounted for 15.9% (77/483) of all patients with intestinal fistula treated in the same period in our department. An average of 8.8 days had elapsed before the final diagnosis of GI fistula was made, during which 73 patients had 1-8 kinds of complications, 48 received 1-5 operations, and 67 were given nutritional support for 6 to 254 days. Thirty patients were cured operatively and 33 (52.4%) spontaneously. The mortality was 18.2%. The etiology, principles of prevention, and management of traumatic intestinal fistula were discussed with emphasis on effective nutritional support and intraabdominal drainage. PMID- 1307337 TI - [10 year-follow up of 2815 patients with resected recto-anal adenomas or polyps]. AB - Ten year-follow up of 2815 patients with resected rectoanal adenomas or polyps revealed recurrence in 225 patients with a rate of 7.99%. The recurrence rate of villotubular adenoma and villous adenoma was 18.26% and 15.79% respectively, the more the volume of adenomas and polyps is, the higher the recurrence, in which the recurrence rate of more than 2 cm in diameter is 19.23% and the recurrence rate of multiple adenoma and polyps had a higher recurrence rate than single ones (17.39% vs 6.88%). Canceration in 10 years was found in 16 patients with a rate of 0.57%. PMID- 1307338 TI - [Effects of shock and reperfusion on multiple organ function after gunshot wounds]. AB - The effects of shock and reperfusion on multiple organ function in gunshot canine model were studied. The results showed that organ function damage even failure of the lung, liver and kidney occurred 24 hours after wound. In some dogs bacterial translocation and increase of lipid peroxidation (LPO) were also found. The experimental findings suggested that the activated free radical system and bacterial translocation may be the underlying pathogenesis of multiple organ injuries and failure. It is possible to establish a model for studying multiple organ failure on this experimental condition. PMID- 1307339 TI - [The diagnosis and treatment of Dieulafoy's ulcer]. PMID- 1307340 TI - Stimulation of renal tubular transport of p-aminohippurate in rats of different ages by treatment with adrenocortical steroids. AB - Treatment with prednisolone or dexamethasone is followed by an increase in renal excretion of p-aminohippurate (PAH) and in accumulation of PAH in renal cortical slices, particularly in 5- and 10-day-old rats with immature kidney function. Treatment with triamcinolone is effective both in immature and in 55-day-old rats. There is no stimulation of PAH transport after treatment with mineralocorticoids (desoxycorticosterone, aldosterone). PMID- 1307341 TI - Effects of phenobarbital on cerebral blood flow in the newborn piglet. AB - To determine the neonatal cerebrovascular effect of a therapeutic dose and a high dose of phenobarbital (Pb), the effect of Pb on cerebral blood flow (CBF) and total brain oxygen consumption (CMRO2) was studied in three groups of awake newborn piglets (aged 1-3.5 days). Group I (control n = 9) received normal saline solution, group II (n = 9) received a therapeutic dose of Pb (15 mg/kg i.v.) and group III (n = 9) received a high Pb dose (45 mg/kg i.v.). Four CBF measurements per piglet using radioactive microspheres (141Ce, 85Cr, 95Nb, 46Sc), arterial blood gases, O2 content, hematocrit and plasma glucose were obtained at 0, 15, 30, 60 min after saline or Pb injections. In all groups, pH, PaO2, PaCO2, blood pressure, heart rate, temperature and plasma glucose remained unchanged except a 14% decrease (p < 0.01) in blood pressure and an increase (p < 0.05) in PaCO2, 60 min after drug injection in groups II and III. Total CBF in group II decreased by 14% (p < 0.05) 15 min after drug injection and was significantly lower (p < 0.05) than control (group I) but returned to baseline after 30 min. High Pb dose progressively lowered CBF by 11% 15 min after drug injection and produced a significant decrease by 20% (p < 0.01) 30 min after drug injection with return to baseline after 60 min. Similar effects were noted in different brain regions (cerebrum and thalamus). CMRO2 remained unchanged in the control group; however, it was decreased by 35% (< 0.01 p > 0.05) 15 min after drug injection and returned to baseline after 60 min. In group III, high Pb dose lowered CMRO2 by 31% 30 min (p = 0.02) after drug injection. Data indicate that Pb exerts a minimal but transient dose-dependent effect on CBF and CMRO2. PMID- 1307342 TI - Placental transfer of phenobarbital: what is new? AB - The placental transfer of phenobarbital was investigated in 35 mother-infant pairs at birth. The drug was administered prenatally to the mothers for maternal epilepsy (group 1, n = 5), gestational hypertension and preeclampsia (group 2, n = 20) and prophylaxis of intraventricular hemorrhage in premature deliveries (group 3, n = 10). The phenobarbital levels in arterial cord blood were 100 +/- 2.8% in group 1, 89 +/- 21% in group 2 and 77 +/- 16% in group 3 with respect to the levels observed in the mothers. The most important factor influencing the transplacental passage was the duration of maternal treatment in the infant of group 1 (r = 0.80, p < 0.01), the gestational age in the infants of group 2 (r = 0.74, p < 0.01) and the arterial cord pH in the infants of group 3 (r = 0.89, p < 0.001). PMID- 1307343 TI - Albendazole and mebendazole uptake by isolated enterocytes. AB - Uptake of albendazole (ABZ) and mebendazole (MBZ) by isolated rat enterocytes was carried out. These drugs, widely used oral anthelmintics, exhibit a scarce water solubility which reduce its absorption by the oral tract. The present study was designed to assess the captation for ABZ and MBZ in different enterocyte populations isolated from upper to crypt villus. The concentration range used for the absorption experiments was within 10-500 microM for both drugs, using DMSO as solvent. The results obtained show the existence of a passive mechanism for the uptake of ABZ and MBZ at concentrations between 10 and 100 microM, with a maximum intake value around 20 microM/mg protein. No differences were found with respect to the cell populations analyzed. The drug uptake levels seem to be higher for MBZ than for ABZ prior to reaching the maximum plateau. PMID- 1307344 TI - Patient-controlled versus conventional analgesia for postsurgical pain relief in adolescents. AB - We performed a randomized nonblinded, cross-over comparison of patient-controlled analgesia (PCA) with conventional intramuscular analgesia in 10 adolescents (13 18 years) undergoing spinal fusion for idiopathic scoliosis. PCA use afforded more effective pain control (p < 0.02) on a 10-point linear pain intensity scale than did intramuscular injections, while causing an equal amount of sedation and no side effects. PCA appears to be a promising technique for providing postoperative pain relief in this group of adolescents. Further studies are needed to define its role for other pediatric conditions. PMID- 1307345 TI - Delayed thromboxane synthesis inhibition, but not cholinergic blockade, reverses group B streptococcus-induced pulmonary hypertension. AB - Anisodamine, an anticholinergic drug, is widely used in China for treatment of infants with septic shock and has been reported to inhibit thromboxane synthesis in cultured cells. Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear. We tested the hypothesis that thromboxane A2 synthesis inhibition with dazmegrel, and cholinergic blockade with anisodamine, would attenuate the later phase of pulmonary hypertension induced by 4 h of group B streptococcus (GBS) infusion. 1 mg/kg of dazmegrel reversed the pulmonary hypertension and slightly increased cardiac output; these hemodynamic improvements persisted for 30-60 min. Plasma thromboxane B2 levels returned toward pre-GBS baseline values after dazmegrel treatment. Thus, thromboxane A2 is still a major mediator of pulmonary hypertension in piglets after 4 h of continuous GBS infusion. 0.5 mg/kg of anisodamine had no significant hemodynamic effect. 2 and 4 mg/kg of anisodamine each caused transient, dose-related decreases in systemic artery pressure; cardiac output also fell after the highest anisodamine dose. Pulmonary hypertension was not alleviated by anisodamine. All hemodynamic changes induced by anisodamine were short-lived and returned to preanisodamine values within 10 min. Anisodamine did not ameliorate thromboxane-mediated pulmonary hypertension in this animal model, and therefore may not inhibit thromboxane synthesis in vivo. The results of this study do not support the use of anticholinergic therapy to improve hemodynamics in GBS sepsis, but do suggest that thromboxane synthesis inhibition may be a clinically useful therapy in advanced GBS sepsis. PMID- 1307346 TI - Synergistic effect of triiodothyronine and dexamethasone on renal tubular transport of p-aminohippurate in rats of different ages. AB - Postnatal maturation of the renal tubular transport of p-aminohippurate (PAH) was verified in rats both in diuresis experiand on renal cortical slices in vitro. Following treatment with various doses of triiodothyronine (T3) or dexamethasone (3 days, once a day), the increase in renal tubular transport of PAH was more distinct in young rats with immature kidney function. The synergistic effects of simultaneous treatment with both hormones indicate differences between T3 and dexamethasone in the modulation of cellular function. PMID- 1307347 TI - Wilson's disease treatment by triethylene tetramine dihydrochloride (trientine, 2HCl): long-term observations. AB - Wilson's disease is an autosomal recessive disorder characterized by an accumulation of a toxic amount of copper in the body. Triethylene tetramine dihydrochloride (trientine, 2HCl) is a new chelating agent that may be effective in the removal of excess copper but long-term efficacy has not yet been investigated. Here we report the use of trientine over more than 8 years in 2 patients with Wilson's disease who could not tolerate D-penicillamine. We found no significant side effect, except a decreased serum iron concentration without clinical symptoms of anemia. In annual examinations at a steady state, the serum copper levels remained below 20 micrograms/100 ml. The 24-hour urinary copper excretion was less than that found using D-penicillamine, while the basal copper excretion, after 5 days abstinence from trientine, was maintained below 100 micrograms/day. Both hepatic and neurological manifestations except bulbar symptoms were recovered without any initial deterioration. PMID- 1307348 TI - Doctors and consumers. PMID- 1307349 TI - Pericardiocentesis: need for haemodynamic monitoring. PMID- 1307350 TI - Value of haemodynamic studies during pericardiocentesis in a cardiac catheterisation laboratory. AB - Pericardiocentesis was performed in 20 patients using a 7F diagnostic catheter in a cardiac catheterisation laboratory under fluoroscopic control, with haemodynamic and electrocardiographic monitoring. This technique offers several advantages over the bedside technique which utilises a sharp needle. The technique utilised for percutaneous aspiration is safe and simple and allows complete drainage of fluid. The haemodynamic monitoring before and after drainage aids in detecting cases of effusive constriction. PMID- 1307351 TI - Methotrexate: clinical and immunological effects in refractory rheumatoid arthritis. AB - Thirty five patients with refractory rheumatoid arthritis were given 7.5 mg of methotrexate (Mtx) every week. Eleven patients had to discontinue treatment either because of adverse effects or unresponsiveness. Twenty four patients showed clinical response and significant improvement in ESR and they continued Mtx for a mean of 25.24 months. Seven patients achieved clinical remission as defined by ARA criteria. Immunological parameeters including IgG, IgM, IgA, lymphocyte subsets (CD3+, CD4+, CD8+ and B), C3 and C4 however, did not show any change during this treatment in any of the groups upto 6 months. There was a significant fall in the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and rheumatoid factor (RF) levels in responders only. PMID- 1307352 TI - G-6PD deficiency in malaria endemic areas of Udaipur District in Rajasthan. AB - Nine thousand four hundred thirty three pyrexial cases were screened for the evidence of Malaria and Glucose-6-phosphate dehydrogenase deficiency among the rural tribal population of seven primary health centres in the malarial endemic areas of Udaipur District in Southern Rajasthan. One thousand four hundred five (P. Falciparum 831 and P. Vivax 574) cases were positive for malaria and 170 for G-6PD deficiency. Incidence of G-6PD deficiency in malaria, when compared to the non-malarial cases revealed statistically insignificant alterations (X2 is calculated to 0.1299 which for 1 degree of freedom gives P > 0.05). PMID- 1307353 TI - Effect of bed time intermediate acting insulin in NIDDM subjects refractory to a combination of sulphonylureas and biguanides. AB - The effect of a single dose of intermediate acting (Lente) insulin given subcutaneously at 9.00 P.M. in 22 NIDDM subjects refractory to a combination of Sulphonylureas and Biguanides was analysed. Euglycemia was achieved and maintained during the study period of three months with a mean insulin requirement of 14.22 +/- 5.98 units/day. Plasma FFA, Total cholesterol, triglyceride and VLDL-cholesterol also showed significant reduction. The level of FFA modulates hepatic glucose production, which in turn correlates positively with the fasting blood glucose. The therapeutic modality of bed time Lente Insulin based on physiological principles is an effective way of achieving glycemic control in NIDDM subjects who have become non-responsive to oral hypoglycemic agents. PMID- 1307354 TI - Sexual and physical growth in Kerala boys. AB - One hundred and fifty males in the age group 10-17 years were studied longitudinally for 2 years to determine their physical and pubertal development. The velocity of linear growth, weight gain and pubertal growth velocities were determined. The relation between peak height velocity and genital stages and between genital stages and pubic hair was determined. It is concluded from this study that 86 percent of normal males reach peak height velocity while in G4 and only 5% will not have achieved peak height velocity by the time G5 is reached. PMID- 1307355 TI - Pharmacokinetics of antiepileptic drugs and its application to therapeutics. PMID- 1307356 TI - Polyol pathway in the pathogenesis of diabetic complications and aldose reductase inhibitors. PMID- 1307357 TI - Epidemiology of gallstones. PMID- 1307358 TI - Cranial diabetes insipidus due to viper bite. PMID- 1307359 TI - Blepharospasm hemifacial spasm and tremors possibly due to isolated caudate nucleus lesions. AB - Isolated caudate nucleus lesions have only rarely been documented to cause focal extrapyramidal dysfunction. Two cases with possible infarcts in the head of left caudate nucleus presenting with contralateral tremors and blepharospasm with hemifacial spasm are reported. The possible mechanisms for such a presentation are discussed. PMID- 1307360 TI - Chicken pox induced pancytopenia and prompt response to high dose intravenous immunoglobulin. AB - This is to highlight the rare complication of pancytopenia following an attack of chickenpox and the favourable response to high dose intravenous immunoglobulin. We are hereby postulating the cause of this refractory pancytopenia as viral antibody mediated event and hence the response to intravenous immunoglobulin. PMID- 1307361 TI - Porencephalic cyst. AB - Porencephalic cyst with seizure is rare. It represents a part of diffuse cerebral maldevelopment. Porencephaly occurs as a result of imbalance between brain growth and its vascular supply and is picked up by CT scan. PMID- 1307362 TI - Electrocardiographic diagnosis of atrial infarction in aluminium phosphide poisoning. PMID- 1307363 TI - Albendazole therapy in ring lesions of neurocysticercosis. AB - Two young epileptics with ring lesions in CT scan were treated with antiepileptic and antitubercular drugs as per original diagnosis. On subsequent evaluation the diagnosis was revised as neurocysticercosis. PMID- 1307365 TI - Left main coronary artery stenosis following angioplasty of the proximal left anterior descending coronary artery--a case report. PMID- 1307364 TI - Thrombocytopenia--a manifestation of HIV-1 infection in a heterosexual male. AB - A 28 years old male with multiple heterosexual contacts presented with bleeding manifestations. Investigations revealed a picture of AIDS-related Thrombocytopenia with primary syphilis. PMID- 1307366 TI - Ventricular fibrillation with hypoglycemia. PMID- 1307367 TI - Extensive CT scan abnormality in Wilson's disease. PMID- 1307368 TI - Resistant Salmonella meningitis treated with ofloxacin--a quinolone compound. PMID- 1307369 TI - Cardiac surgery in congenital heart disease. PMID- 1307370 TI - Respiratory variation in ST depression. PMID- 1307371 TI - Irritable heart in young. PMID- 1307372 TI - Typhoid fever, not responding to ciprofloxacin therapy. PMID- 1307373 TI - Viral encephalitis--overdiagnosed, undertreated. PMID- 1307374 TI - Gene therapy. PMID- 1307375 TI - Primary amoebic lung abscess. PMID- 1307376 TI - Cryptococcal meningitis in a patient with Hodgkin's lymphoma. PMID- 1307377 TI - Preweaning feeding mechanisms in the rabbit. AB - Muscle contraction patterns and mandibular movements of infant rabbits during suckling and chewing were compared. Oral muscle activity was recorded by fine wire electromyography, while jaw movements and milk bottle pressure were registered. Suckling and mastication have a comparable cycle duration and share a common pattern of oral muscle activity which consists of a succession of a jaw closer burst, during which the jaw closes and undergoes a power stroke (in mastication), a suprahyoid burst with a stationary or slightly opening jaw and a digastric burst with fast jaw opening (the power stroke of suckling). Compared to suckling, mastication shows decreased jaw opener activity, increased jaw closer activity, development of jaw closing activity in the lateral pterygoid, and increased asymmetry in the masseter by development of a new differentiated motor pattern on the working side. The study shows that the suckling motor pattern enables the infant rabbits to change to chewing with just a few modifications. PMID- 1307378 TI - Measurement of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus. AB - A technique has been developed for prelabelling and permeabilisation of guinea pig uterine myocytes to enable measurement of arachidonic acid release/phospholipase A2 activity in cells with intact membranes. Intact cells were prelabelled with [3H]inositol or [3H]arachidonic acid for measurement of phospholipase C and A2 respectively. In intact cells 10 nM endothelin-1 or 1 microM bradykinin stimulated both inositol polyphosphate and arachidonic acid release, whilst 1 microM oxytocin, arginine vasopressin or histamine were without effect. In Streptolysin-O permeabilised myometrial cells calcium-stimulation of inositol polyphosphate and arachidonic acid release was detected between 10 microM and 1 mM free calcium. The patterns of inositol polyphosphate and arachidonic acid release were broadly similar. Responses to 1 mM calcium were not detected in intact cells not treated with Streptolysin-O. For arachidonic acid release the K0.5 for calcium activation was about 7 microM, a level above that normally likely to be found in the uterine myocyte. Hence it is concluded that unless there are high local concentrations of calcium close to the plasma membrane, calcium is unlikely alone to be the primary regulator of arachidonic acid release and phospholipase A2. PMID- 1307379 TI - Changes in phospholipase A2 in myometrium of the guinea pig uterus during pregnancy. AB - Phospholipase A2 activity has been measured in membrane and cytosolic fractions from non-pregnant and pregnant guinea pig myometrium has been studied. Enzyme activity was measured with 1-stearoyl-2- [3H]arachidonoyl-phosphatidylcholine exhibiting Michaelis-Menton kinetics with Km of 83.8 +/- 21.6 and 53.2 +/- 14.1 for membrane and cytosolic enzymes respectively. Fractionation of the myometrium from non-pregnant guinea pigs suggested that 35% of the activity was membrane associated compared with 20% (P < 0.01) in tissue from pregnant animals. In the presence of 1 mM calcium total activity rose from 3.03 +/- 0.41 to 1737 +/- 368 nmol/h per uterus between non-pregnant and late pregnancy. Calcium activated the membrane enzyme, but the effect was greater late in pregnancy with almost a 6 fold increase in activity at 1 mM calcium compared with a doubling in membrane from non-pregnant guinea pigs. The K0.5 for calcium activation was about 150 microM. Immunoblotting with anti-human-110 KDa phospholipase A2 showed in guinea pig uterus a 34 KDa form of the enzyme that, consistent with changes in activity, showed a fifteen-fold increase in quantity between non-pregnant and late pregnancy. The data are consistent with dramatic increases in the capacity for arachidonic acid release and prostaglandin production in the guinea pig myometrium late in pregnancy. PMID- 1307380 TI - 45Ca-efflux in embryonic chick heart and its modification by caffeine and ryanodine. AB - Ontogenic changes in the kinetics of exchangeable cellular calcium were studied in embryonic (ECV) and post-hatch (PHCV) chick ventricular tissue by monitoring 45Ca-efflux. The isolated whole ventricle (5 & 7 days ECV) or ventricular strips (12 & 18 days ECV and 1-2 days PHCV) were "loaded" with 45Ca (37 degrees C) and then passed through a series of tubes containing efflux solution (4 degrees C) to determine 45Ca-efflux. Curve 'peeling' of the efflux curve indicated existence of 3 kinetically distinct components of exchangeable cellular Ca2+ compartments: C1, C2 & C3. The size of C1, which was the largest in 5 & 7 days ECV decreased significantly to become minimum in 18 days ECV & PHCV. The rate constant of this compartment, however, reduced with the age of the embryo. In contrast, the size of C3 increased with the embryonic development to become the largest in 18 days ECV & PHCV. An increase in the rate constant of this compartment was also observed during embryogenesis. The size and rate constant of C2 remained unaltered during development. However, the increase in size of C3 during embryonic development indicates differentiation of Ca2+ storage sites, like sarcoplasmic reticulum (SR), during the later stages. Caffeine (10 mM) and ryanodine (10 microM) enhanced fractional escape rate during slow phase (ie 120 180 min) of efflux at all developmental stages. The magnitude of enhancement increased during later stages of development indicating greater prominence of SR with the age of embryo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307381 TI - The effect of maternal undernutrition on the growth and development of the guinea pig placenta. AB - Fetal growth is known to be correlated with the size of the placenta and the exchange surface area. Reduction in the growth of the materno-fetal exchange surface areas may be a mechanism by which the effects of maternal undernutrition on fetal growth are mediated. In the compact placenta of the guinea pig the exchange surface is equivalent to the peripheral labyrinth. The effect of a 40% reduction in maternal feed intake on the growth of the peripheral labyrinth was investigated in pregnant guinea pigs between gestational days 25 and 65. Fetal and placental weights were significantly reduced in the last trimester by 32% and 38% respectively (P < 0.01). Placental efficiency in early gestation was significantly impaired in restricted animals but equivalent to ad lib. fed controls by the last trimester. The volume of the peripheral labyrinth increased as a percentage of the total placental volume with gestational age. Restricted placentae tended to be composed of a smaller volume of peripheral labyrinth tissue in early gestation. It is suggested that maternal undernutrition results in an impaired or delayed expansion of the peripheral labyrinth in early gestation causing a reduction in placental efficiency. By the last trimester the weight of the peripheral labyrinth of restricted animals was reduced by 33% (P < 0.05). The weight of the peripheral labyrinth was also significantly correlated with fetal weight is limited by the size of the peripheral labyrinth in the later stages of gestation. PMID- 1307382 TI - The effects of maternal undernutrition on maternal and fetal serum insulin-like growth factors, thyroid hormones and cortisol in the guinea pig. AB - The insulin-like growth factors (IGF-I and -II) are potential mediators of the effects of maternal undernutrition on fetal growth and muscle development. The effects of a 40% reduction in maternal feed intake on serum levels of the IGFs, the thyroid hormones and cortisol, were investigated for the last two trimesters (day 25 to birth). This level of undernutrition is known to cause a 35% reduction in fetal and placental weights, and a 20-25% reduction in muscle fibre number. Maternal IGF-I level was greater than non-pregnant levels on day 25 gestation, in both control and restricted dams, and declined with gestational age. The increase in IGF-I level in the 40% restricted group was approximately two-thirds that of control animals. Fetal serum IGF-I was also reduced in undernourished fetuses throughout gestation. Maternal IGF-II did not change with gestational age and was unaffected by undernutrition. Fetal IGF-II reached a peak at day 55 of gestation, this peak was greatly diminished by maternal feed restriction. Both IGF-I and IGF II tended to be related to fetal, placental and muscle weights at day 65 of gestation. Thyroid hormone concentration declined in maternal serum and increased in fetal serum with increasing gestational age. Levels were not significantly affected by undernutrition. Both triiodothyronine (T3) and thyroxine (T4) were correlated with IGF-I in maternal serum (P < 0.05), but not in fetal serum. Cortisol levels were elevated by undernutrition in both maternal and fetal serum, and increased with gestational age. Cortisol was inversely correlated with serum IGF-I in both maternal and fetal serum. Maternal serum IGF-I may mediate the effects of undernutrition on fetal growth by affecting the growth and establishment of the feto-placental unit in mid-gestation. Fetal IGF-I may mediate the effects on muscle growth, whereas IGF-II seems to be related to hepatic glycogen deposition. Cortisol may play a role via its effect on the IGFs, but the thyroid hormones are unlikely to be important until the late gestation/early postnatal period. PMID- 1307383 TI - Hemoglobin H disease in children. AB - One hundred and ten children with hemoglobin H (Hb H) disease who attended the hematology unit of the Department of Pediatrics at Songklanagarind Hospital from 1982 to 1988 were studied. Hb Constant spring (Hb CS) was found in 55 patients. Four patients, two with Hb CS, were diagnosed during the newborn period. Anemia and jaundice were the main symptoms in three neonates, while the fourth one was found to have anemia with hepatosplenomegaly. Nine infants were diagnosed in the first year of life with the chief symptoms of anemia with or without fever. Two of them needed blood transfusions. Hb H was found in only three infants, while Hb Bart's was the constant finding in every infant. The Hb H children with Hb CS had a more severe clinical course than the group without Hb CS. The levels of Hb at steady state were found to be lower and the reticulocyte counts, red cells with inclusion bodies and Hb H were higher in patients with Hb CS. The clinical picture of acute hemolysis in Hb H children can be found in the neonatal period and the difference in clinical severity between the two genotypes of Hb H disease seems to develop from the first year of life. PMID- 1307384 TI - Evaluating the UVA protection of commercially available sunscreens. AB - Because the protection factor of sunscreens concerns only UVB protection, usually only a little is known about the protection offered in the UVA range. Photoprotection against ultraviolet A (UVA) by five commercially available sunscreens and their components was evaluated in humans, with erythema and pigmentation used as end points. Because UVA-induced tanning obscures a UVA erythema, quantitative analysis of UVA-erythema cannot be used as the end point in this study. All products provided low UVA protection factor (1.02-1.9). The sunscreen which contain 3 per cent Parsol 1789 was the most effective product and significantly better than the other (p < 0.0001). PMID- 1307385 TI - Transvaginal sonographic features in ectopic pregnancy. AB - A retrospective review of the transvaginal sonograms of 37 women with confirmed ectopic pregnancy was performed to characterize the findings from transvaginal sonography and correlate operative findings with sonographic features. Thirty-six of the 37 ectopic pregnancies were tubal pregnancies. Intrauterine findings showed an absence of gestational sac in all cases and a pseudosac in 1 case (7.14%). An ectopic gestational sac with a live embryo was documented in 2 cases (5.41%) and with embryo or yolk sac in 6 cases (16.22%) and nonspecific adnexal mass in 30 cases (81.08%). Fluid in the cul-de-sac was found in 22 cases (59.46%). Transvaginal sonography provides better access to the pelvic organ and allows a clear view of the uterus and adnexa, with no need to fill the bladder. Excellent visualization of the endometrial cavity permits the detection of even a very early intrauterine pregnancy and clearly shows the gestational sac where it is outside the uterine cavity. Blood and other fluids in the cul-de-sac can also be seen easily. This technic has reduced patients' risk by minimizing delay in diagnosis and treatment. PMID- 1307386 TI - High-frequency flow interruption in the rescue of preterm infants with severe RDS. AB - High-frequency flow interruption (HFFI) was used successfully to rescue three preterm infants with severe respiratory distress syndrome (RDS) whose clinical condition continued to deteriorate while on the conventional mechanical ventilation. Had the HFFI not been used, the survival chances might have been 25 per cent for Case 1 and 2, and 45.5 per cent for Case 3. A dramatic, immediate, and sustained improvement in ventilation and oxygenation was demonstrated once the critical frequency and amplitude of HFFI were established. Bronchopulmonary dysplasia which was already evidenced in one infant before the HFFI attempt was detected in two infants. This study demonstrates that HFFI is capable of achieving adequate gas exchange and improving survival in infants with severe RDS. PMID- 1307387 TI - Intradermal simulated rabies postexposure prophylaxis using purified chick embryo rabies vaccine. AB - The antibody responses of 65 volunteers receiving an i.d. regimen (0.1 ml given at two different sites on days 0, 3, 7 and 0.1 ml given at one site on days 30 and 90) were compared with a control group of 35 volunteers receiving the standard i.m. regimen. By day 14, seroconversion was observed in all vaccinees in both groups. Geometric mean titers remained higher than 0.5 IU/ml throughout the study period. At the end of the observation period on day 365, antibodies persisted in all subjects. The multisite i.d. PCEC regimen has been proved as immunogenic as the standard i.m. regimen. Both regimens were well tolerated. Thus, it would be the effective and cheapest available rabies postexposure treatment using tissue culture vaccine. PMID- 1307388 TI - Treatment of severely head injured patients with absence of basal cisterns on initial CT scans. AB - Sixty-four severely head injured patients with absence of basal cisterns on initial CT scan were studied from January 1986 to March 1989. None had good recovery at 6 months follow-up period. The result from logistic regression analysis pointed to the GCS at 24 hours following injury as an independent, significant outcome predictor. Conventional treatment is not suitable for these patients. Earlier and more aggressive therapy should improve their outcome. PMID- 1307389 TI - Lymphocyte-bearing ferritin in beta-thalassemia/Hb E. AB - Flow cytometric analysis of lymphocyte subsets and lymphocyte surface ferritin shows no significant difference in the number of total T-cells, B cells, NK cells, helper T-cells (CD 4), suppressor T-cells (CD 8) and CD 4/CD 8 ratio among normal subjects (n = 11) and Hb E trait (n = 6), beta-thalassemia (beta-thal) trait (n = 5), neither in normal and nonsplenectomized patients with beta-thal/Hb E (n = 10) except B cells and CD 4. There is a significant reduction in lymphocytes surface spleen-type and heart-type ferritin in patients with beta thal/Hb E when compared to normal subjects. No difference can be seen among patients with beta-thal/Hb E, beta-thal trait and Hb E trait. This low percentage of lymphocyte-bearing ferritin suggests a negative relationship between ferritin on the cells' surface and high circulating ferritin normally associated with thalassemic patients. PMID- 1307390 TI - Liver abscess and necrosis following portoenterostomy: a case report. PMID- 1307391 TI - True 47,XXX in a patient with premature ovarian failure: the first reported case in Thailand. AB - A case of triple-X female with premature ovarian failure was reported. The patient was a 23-year-old, single, Thai woman who presented with primary amenorrhea, incomplete development of the secondary sex characteristics, elevated levels of serum gonadotropins, and decreased estrogen concentration. Immunological abnormalities were not identified by antinuclear antibody, rheumatoid factor, antimicrosomal antibody and antithyroglobulin antibody studies. Cyclic estrogen-progestin was given and withdrawal bleeding occurred. The present case represents the utilization of chromosomal analysis in a patient with delayed sexual development, or primary amenorrhea and elevated serum gonadotropin levels. PMID- 1307392 TI - Post-polio syndrome: a review and case report. AB - A 21-year-old Thai man presented with progressive weakness and atrophy of both hands for 2 years. His left leg was atrophic and weak secondary to poliomyelitis since he was 8 months old. Physical examination showed that there was atrophy of both hands and forearms as well as left leg. Sensation was normal. Deep tendon reflexes were normal except for hyporeflexia of left leg. EMG showed chronic denervation pattern in the recent atrophic muscles and in normal power muscles. Motor and sensory nerve conductions were normal. Biopsy of forearm muscle revealed degeneration and fibrosis of muscle fibers. These findings were compatible with post-polio syndrome (PPS) which presents in patients with late paralysis following poliomyelitis. It is not a form of amyotrophic lateral sclerosis although some clinical similarities exist. Weakness from PPS may lead to musculoskeletal pain and increased functional disability. Proper rehabilitation program is to maintain his functional status and allow him to continue to live as independently as possible by regular exercise without stressing joints and muscles. PMID- 1307393 TI - A study of the incidence of stress and anxiety related health problems among the dependants of RAF personnel during the Gulf War. AB - This study set out to investigate the problems suffered by wives of RAF servicemen who were active in the Gulf War (Jan-Feb 1991). A sample of 12 women were given a semi-structured interview which sought their feelings about being separated from their husbands under such circumstances, and their views on life in the services in general. In addition, a number of health professionals who dealt with the women during this time were also interviewed. The results demonstrate that the women were suffering from the effects of severe stress, with 75 per cent at risk of developing serious illness. The effects of the stress touched many aspects of their emotional, social and family lives. Many negative aspects of life in the services were also identified. The author concludes that there is a need for formal support for these women at all times when their husbands are in the RAF, and not just in times of crisis. PMID- 1307394 TI - Methicillin resistant Staphylococcus aureus and its implications for nursing practice: a literature review. AB - The subject of methicillin-resistant Staphylococcus aureus (MRSA) and its implications for nursing practice are reviewed. Resistance of Staphylococcus aureus to antibiotics, and the emergence and incidence of MRSA both in the United Kingdom and abroad, are examined. Modes of transmission of MRSA by transfer of affected patients and, specifically, cross infection by staff are reviewed with methods to prevent cross infection, including screening of staff, handwashing techniques, barrier and cohort nursing, being examined. The costs of an MRSA outbreak, both financially and psychologically, to staff and patients are discussed. Guidelines for the control of epidemic MRSA are explained in the context of the above topics, and all areas are related to improving nursing practice. PMID- 1307395 TI - Management and leadership in Australian nursing homes. AB - This paper is based on the outcomes of a study undertaken by Deakin Institute of Nursing Research for the Department of Community Services and Health between 1988 and 1990 (1). The study, which looked at the relationship between skills mix and resident outcomes, involved gathering data from 200 nursing homes in four Australian states using questionnaires and a case study approach. One of the major findings related to the importance of the management and leadership style on the outcome of quality of care and life within the nursing home. The pivotal role of the senior nurse (ie the director of nursing or charge nurse) in affecting high quality is consistently reported in the literature and this was confirmed by the study. Factors drawn from the quantitative and qualitative parts of the study, which make an important contribution to the quality of care experienced by residents, included the director of nursing's attitude, commitment and interpersonal skills. Also important were the ideology of the staff, team cohesiveness and positive attitude and an overall staffing environment which adheres to an agreed philosophy and is stable, satisfied and friendly. All of these were found to be influenced by the senior nurse. PMID- 1307396 TI - Evaluation of a computerised nursing care planning system in two small hospitals. AB - This paper describes an evaluation study of a computerised nursing care planning system in two small hospitals. A pre/post test design was used, incorporating a variety of measures. The results of the study do not allow any firm conclusions to be drawn about the effects of the system itself, and need to be considered within the wider context of changes occurring both within nursing and the National Health Service (NHS). Further research should be contemplated to include large sample size, the use of a control and objective independent measures of quality. PMID- 1307397 TI - [Trypanosoma cruzi in the milk of women with chronic Chagas disease]. AB - Breast milk secretion is one of the possible alternative mechanisms of transmission of the parasitosis caused by Trypanosoma cruzi, but it is still needed to define its importance in terms of public health. On this aim we searched for the presence of this protozoal organism in the colostrum and breast milk of 40 women with Chagas' disease, through direct observation, culture and inoculation. We never found parasite; perhaps it might be possible with the use of more efficient procedures and a larger number of cases. PMID- 1307398 TI - [Urinary citrate determination in normal persons and in patients with recurrent urinary calculi]. AB - The presence of citric acid in urine and its ability to bind calcium ions forming a soluble complex are well recognized and has led to the suggestion that citric acid may play an important role in preventing renal calcium stone disease. In this study the 24-hour urinary excretion was measured with a specific enzymatic method in 48 normal subjects and in a group of 46 non selected patients with recurrent urolithiasis. Hypocitraturia was detected in 18/46 patients (39.1%) and was the unique metabolic abnormality in 6 (13%). PMID- 1307399 TI - [Functional electric stimulation (FES) in cerebral palsy]. AB - Our study concerns a patient with cerebral palsy, submitted to conventional occupational therapy and functional electrical stimulation. The results as to manual ability, spasticity, sensibility and synkinesis were satisfactory. PMID- 1307400 TI - [Fatal strongyloidiasis in an immunodepressed patient following renal transplantation]. AB - Occurrence of fatal hyperinfection with Strongyloides stercoralis in an immunodepressed patient after kidney transplantation is reported. Physiopathology of the illness is discussed and the seriousness of the hyperinfection syndrome is stressed. Endoscopy with duodenal biopsy is useful for the establishment of diagnosis. PMID- 1307401 TI - [Acute lethal intoxication caused by mercury vapor]. AB - Nowadays mercury poisoning usually results from the oral ingestion of methylmercury or from inhalation of mercury vapor. Mercury intoxication in a gold prospector after inhalation of mercury vapor is described. The patient presented a history of fever, tachypnea and headache. Despite the treatment with dimercaprol, penicillamine and intensive supportive care the patient died with symptoms of acute respiratory distress. PMID- 1307402 TI - [Role of oxygen free radicals in the physiopathology of rheumatoid arthritis]. AB - The authors present a review of the mechanisms of free radicals production and report the results of "in vivo" and "in vitro" studies correlating these agent with the physiopathologic changes of the rheumatoid arthritis. The data reviewed in this paper support the idea of the participation of free radicals in the articular lesion. However new studies are necessary to determine the contribution of free radicals on disease development, chronicity and the efficacy of antioxidant agents. PMID- 1307403 TI - [Clinical use of immunoglobulins]. AB - This article is a review of literature about the clinical use of immunoglobulins and the main purpose of this paper is to direct those who prescribe theses products. In this review are analysed and discussed the principal indications for the use of these compounds, the complications and the safety of the immunoglobulins. PMID- 1307404 TI - [Medical schools in Brazil]. AB - In the 1970-1980 period there was a considerable increase in the number of institutions of higher education in Brazil which are located mostly in the Southeast region of the country. The distribution of medical schools is not correlated with the distribution of population. In 59 out of 76 medical schools the internship has a duration of two semesters, in five schools three, and in 12 schools four semesters. The medical residence programs are, with 68% of 9,644 total vacancies, considerably concentrated in the Southeast region. PMID- 1307405 TI - [Systemic lupus erythematosus in the aged: clinical and laboratory characteristics]. AB - The clinical and serologic characteristics of 199 systemic lupus erythematosus patients with early and late onset of disease were compared to determine if the disease in the older age group defines a specific subset of SLE. This study demonstrated that SLE in the elderly patients exhibits peculiar clinical features with a high frequency of muscular involvement (p < 0.05) and low frequency of cutaneous manifestations (p < 0.001) and alopecia (p < 0.02). Moreover, the most frequent clinical manifestation was muscular pain and stiffness, arthritis and weight loss (over 10 kg). This condition is often hard to distinguish from polymyalgia rheumatica or underlying malignancy. The frequency of autoantibodies was similar in both groups. The absence of anti-La was surprising, however it was confirmed by "Western blotting". The symptoms of late onset SLE are not very prominent however the diagnosis should be considered in order to avoid delays in treatment. PMID- 1307406 TI - Modulation of parasitemia and antibody response to Trypanosoma cruzi by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae). AB - Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10(3) T. cruzi on day O. Parasitemia, mortality and antibody response as measured by direct agglutination of trypomastigotes were observed. Two hundred mg doses of cyclophosphamide resulted in higher parasitemia and mortality as well as in suppression of the antibody response. A single dose of 20 mg enhanced antibody levels on the 20th day after infection, while an additional dose did not further increase antibody production. Parasitemia levels were not depressed, but rather increased in both these groups as compared to untreated controls. Passive transfer of hyperimmune C. callosus anti-T. cruzi serum to cyclophosphamide immunosuppressed animals resulted in lower parasitemia and mortality rates. These results indicate that the immune response plays an important role in the resistance of C. callossus to T. cruzi. PMID- 1307407 TI - [Occurrence of Strongyloides stercoralis in patients with acquired immunodeficiency syndrome (AIDS)]. AB - A comparative study on the occurrence of Strongyloides stercoralis larvae in 554 patients with AIDS and in 142 patients suffering from infectious diseases other than AIDS was conducted during the period from January 1987 to December 1988. The two groups was constituted by male individuals in-patients at Emilio Ribas Hospital--Sao Paulo. Faeces samples from 696 patients were submitted to spontaneous sedimentation method and Rugai method. The data obtained from the present investigation demonstrated a similar prevalence of Strongyloides stercoralis in both groups (p > 0.05) indicating no significant statistical differences. PMID- 1307408 TI - First register of Biomphalaria straminea Dunker, 1848, in Santa Catarina State. AB - The first register of Biomphalaria straminea, vector species of schistosomiasis, in Santa Catarina State, South Brazil is described. The specimens were obtained from two ornamental aquaria of private residences. In both cases the ornamental plants and/or fishes were bought from the same supplier. The presence of this species was later confirmed in the farm where these plants and fishes are cultivated, in the city of Governador Celso Ramos, also in Santa Catarina State. The occurrence in natural environments was later detected in two different places of the Island of Santa Catarina. PMID- 1307409 TI - [Spotted fever: isolation of Rickettsia from a skin biopsy sample]. AB - A 2 years old child living in an area of the State of Sao Paulo, known in the past as endemic for rickettsiosis developed clinical evidences of spotted fever after a tick bite. Rickettsiae were isolated from guinea pigs inoculated with a skin homogenate. In sera tested by indirect immunofluorescence with Rickettsia rickettsii standard antigen, IgG specific antibody titers raised from 1:512 in the first sample to 1:2048 in the third one; IgM specific antibody titer was 1:128 in the three samples. Also positive were sera obtained from the inoculated guinea pigs. In the last 20 years no other case of rickettsial spotted fever has been confirmed by isolation of the agent in Brasil. To our knowledge, there are no previous reports of isolation of Rickettsiae through inoculation of skin biopsy homogenates. PMID- 1307410 TI - Standardization of dot-ELISA for the serological diagnosis of toxocariasis and comparison of the assay with ELISA. AB - The dot-enzyme-linked immunosorbent assay (dot-ELISA) was standardized using somatic (S) and excretory-secretory (ES) antigens of Toxocara-canis for the detection of specific antibodies in 22 serum samples from children aged 1 to 15 years, with clinical signs of toxocariasis. Fourteen serum samples from apparently normal individuals and 28 sera from patients with other pathologies were used as controls. All samples were used before and after absorption with Ascaris suum extract. When the results were evaluated in comparison with ELISA, the two tests were found to have similar sensitivity, but dot-ELISA was found to be more specific in the presence of two antigens studied. Dot-ELISA proved to be effective for the diagnosis of human toxocariasis, presenting advantages in terms of yield, stability, time and ease of execution and low cost. PMID- 1307411 TI - [Mansonelliasis in the southeast Venezuelan Orinoquia region]. AB - Physical exam and skin biopsy were performed and peripheral blood samples drawn from 10% of the inhabitants of 26 jungle villages of the State of Bolivar, Venezuela. One hundred and fifty three Indians and an inhabitant of mixed blood from 13 different communities were found to be infected with mansonelliasis representing a global index of 36.40% in the endemic area. The parasitosis was found to be concentrated in three areas. The largest, located in the southwest of the country and forming part of an extent infected area embarking neighboring parts of Venezuela and Brazil, contains villages with a parasite index of 80.76% and 94.44%. A second focus is located in the southeast, its carriers, as those of the first, are infected with Mansonella ozzardi. In a third, central eastern focus infections with Mansonella pertans were found. The patients infected with M. ozzardi were apparently asymptomatic and their physical exam was normal, even though individual parasite densities up to 30,000 microfilariae/ml blood and 22,000/gr skin were found. PMID- 1307412 TI - Massive infestation by Ascaris lumbricoides of the biliary tract: report of a successfully treated case. AB - This is a report of a 25 years old black woman from the city of Sao Paulo, Brazil, who developed acute obstructive cholangitis of Ascaris lumbricoides with septicemia and multiple hepatic abscesses. The patient had sickle cell trait and normal delivery 3 months ago. Massive infestation of the biliary tract by Ascaris lumbricoides was diagnosed by abdominal ultrasonography and endoscopic retrograde cholangiography. Sixty worms were removed from the common bile duct and hepatic abscesses were drained by surgery. The infectious process was polymicrobial. The patient's recovery was complete after a long evolution with a wide spectrum antibiotic therapy. New surgeries were needed to remove residual worms in the biliary tract. The diagnostic methods, clinical-biochemical features and also the clinical and surgical management are presented. The biliary ascariasis pathophysiology is commented. PMID- 1307413 TI - Trypanosoma cruzi: course of infection in platelets-depleted mice. AB - The effect of platelet depletion on the course of Trypanosoma cruzi infection in BALB/c mice was investigated. Thrombocytopenia was achieved by inoculation of rabbit anti-platelet IgG during the parasitemic phase of the infection. The number of parasites in the blood of anti-platelet IgG treated was significantly higher than that of non-treated control mice, during the phase of high parasitemia. Cumulative mortality of platelet-depleted mice was consistently but not significantly higher than that of control mice up to the 32nd day of infection; from the 33rd day on they were equivalent, no mortalities occurring from then on, until observations were discontinued on the 60th day. These results suggest that platelets participate of the mechanisms of parasites removal from the bloodstream, but do not have an effective role in the mechanisms of defence against T. cruzi, during the acute phase of infection. PMID- 1307414 TI - [Epidemiology of latrodectism in the province of Buenos Aires, Argentina]. AB - Epidemiological data related to Latrodectus bites over a 10-year period (1979 1988) in Buenos Aires Province, Argentina, are presented. Data on distribution of accidents by year, month, sex, residence of person bitten and general symptomatology are given. Statistical analysis showed a mean of 28.1 bites cases per year, 80% in males, most of whom were farm workers. The Latrodectus bites were localized in arms, pelvic waist and legs. Forty-six per cent of bitten persons visit the clinic within 1 to 3 hours after the incident, and only 15% capture the animal responsible for the accident. PMID- 1307415 TI - [The relationship between paracoccidioidomycosis and alcoholism]. AB - The relationship between alcoholism and paracoccidioidomycosis was evaluated by the case-control method. The alcohol consumption of 4 groups of patients was compared: 50 patients with chronic paracoccidioidomycosis, 20 patients with the acute or subacute form of this mycosis and their respective control groups of hospitalized patients, each case matched by sex and age. Between September 1986 and July 1988 the cases and their controls were interviewed by one and the same investigator using a questionnaire on drinking habits: quantity and type of beverage consumed, time of onset and frequency of use and whether they had manifested symptoms of inebriation or of alcohol dependence previously. As compared with control patients, the mean daily ingestion of alcohol in excess of 60 ml was more frequent in the chronic paracoccidioidomycosis group (50.0% x 30.0%). These patients also preferred to drink sugar cane brandy more frequently (89.4% x 68.3%). When the average daily consumption of ethyl alcohol exceeded 100 ml, most patients presented a recurrence of infection during or after antifungal therapy. In the acute-subacute paracoccidioidomycosis group, 64.3% of the patients reported inebriation on one or more occasions, versus 17.6% in the respective control group. The results suggest that alcoholism can be a predisposing factor to paracoccidioidomycosis and, probably, accounts for a worse prognosis for this infection. PMID- 1307416 TI - [Identification of mycoplasma by the growth inhibition of samples isolated from cell cultures]. AB - Cell cultures must be continuously screened for the presence of mycoplasma because, although these microorganisms sometimes pass unnoticed, they may cause chromosomic alterations and interfere with viral replication, antibody and interferon production etc. The International Organization for Mycoplasmology (IOM) recommends the isolation and identification of mycoplasma with a view to the detection of the origin of the infection and the improvement of the quality of the cultures. In this paper, 37 samples belonging to 27 cell lines contaminated with mycoplasma were assayed by the growth inhibition test. It is known that Mycoplasma orale is the most common human mycoplasma contaminant of cell cultures, the major vehicle of contamination being mouth pippeting, while commercial bovine serum in the main source for Mycoplasma arginini and Acholeplasma laidlawii. M. arginini was found in 18 (48.65%) of the cell samples tested, A. laidlawii in 15 (40.55%), and M. orale in two (5.40%). Two other samples could not be identified by the antisera used (antisera against M. arginini, M. orale, Mycoplasma hyorhinis and A. laidlawii) their characteristics being "fried egg" colonies, digitonine sensitivity, Dienes stained, positive glucose catabolism, negative arginini hydrolysis, and negative tetrazolium reduction. No more than one type of mycoplasma was found in each cell culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307417 TI - [Cognitive changes in workers at a data processing company]. AB - A study of 191 data processing workers undertaken in Porto Alegre, Brazil, in 1989, is presented. The relationship between complaints of loss of memory and their respective scores on cognitive testing in three groups of workers, one with automatized repetitive activities and two others with diversified activities, is analysed. The scores and complaints are compared with the results of a screening test for psychiatric disorders in order to verify the influence of this confounding factor. No significant evidence of cognitive problems was found despite the high prevalence of complaints of memory loss in this population (65.4%). There is a significant statistical association between these complaints and the scores of the psychiatric testing. It is suggested that futures studies should emphasize psychiatric analysis with a view to clarifying the complaints of Data Processing workers. PMID- 1307418 TI - [Evaluation of dietary intake of calcium in adult subjects with idiopathic arterial hypertension]. AB - The calcium-intake relationship with other alimentary and anthropometric variables was investigates in a group of 60 adult (19-75 year-old) subjects, 50 females and 10 males, with essential arterial hypertension (DAP > 90 mmHg). The calcium intake was assessed by three different protocols: 24-hour food intake recall, food-frequency questionnaire and 3 day self-food intake register, repeated along with anthropometric measurements on three different occasions (2 15 month-intervals). The calcium intake assessed by the three methods, as well as the anthropometric data, were statistically similar on all three occasions. The mean data were then compared with those form the control, composed of 75 healthy subjects matched with the hypertensive group by age and sex. The patients ingested less calcium (mean +/- SD) than the controls on the daily (517 +/- 271 x 740 +/- 353 mg/d) and body-weight (8.1 +/- 5.0 x 11.4 +/- 5.9 mg/kg/d) basis. Among the males the calcium intake was the only difference found between groups and could be attributed to the lower intake of calcium-rich foods. The hypertensive females showed also higher lean-body mass (Body-mass index and arm muscle circumference). Thus the calcium intake discriminated both groups being associated with changes in other nutritional parameters only in females. PMID- 1307419 TI - [The basic network of health services: physicians and their representation regarding the service]. AB - This article aims to analyse the representations of doctors of public sector in Campinas, SP, Brazil, taking as reference the process of decentralization which the health reform being undertaken in Brazil is undergoing. It is assumed that the success of this reform will depend largely on the attitude that these doctors show towards its various aspects. The following subjects were then focused on: the policies and management of the health services, the health-disease process, the doctor-patient relationship and labour process as it affects the health team. PMID- 1307420 TI - [Changes in physical, chemical, and microbiological characteristics of brines applied in the salting of mozzarella cheese during the period of utilization]. AB - Variation of the physical, chemical and microbiological characteristics of brines during their utilization for salting mozzarella cheese. Forty brine samples used for submersion salting of mozzarella cheese in a dairy industry in the State of S. Paulo, Brazil, were analysed for the purpose of discovering the variation in the physical, chemical and microbiological characteristics observed over their period of utilization. The mean values preparation up to the 21st day of utilization of pH, sodium chloride and protein concentration varied from 7.21 to 5.76, from 27.1 to 24.5 and from zero to 0.126 mg/ml, respectively over the period from their. The mean values of the mesophilic microorganism counts and of the total and fecal coliforms MPN varied from 5.8 x 10 CFU/ml to 6.9 x 10(4) CFU/ml, from zero to 1.6 x 10(5)/100 ml and from zero to 1.1 x 10(5)/100 ml, respectively. Moreover, the mean values of mould and yeast and Staphylococcus positive coagulase counts varied from 0.4 x 10 CFU/ml to 2.0 x 10(3) CFU/ml and from zero to 1.3 x 10 CFU/ml, respectively. The results obtained suggest that the hygienic conditions during the preparation and the utilization of the brine were not satisfactory so that they may represent an important source of contamination for the cheeses. The quality of the product may be harmed, as a result of this fact, in such a way as to represent a potential hazard for the health of the consuming population. PMID- 1307421 TI - [Evaluation of nutritional status of adult middle class healthy subjects. Energy and protein intake, anthropometry, blood biochemical tests, and immunocompetence tests]. AB - Nutritional status was assessed in 151 middle-class healthy adult individuals (69 medical students, 18-29 y, 34 males, 35 females); 48 university personnel, 30-49 y, 24 males, 24 females; and their older relatives, 34 subjects, 50-79 y, 19 males, 15 females) living in Botucatu, S. Paulo. Methods included anthropometric measurements, energy and protein intakes, blood biochemical analyses and cutaneous delayed hypersensitivity tests. Anthropometric measurements showed higher values in men, with the exception of the triceps skinfold thickness (higher in women) and of the arm fat area (higher in the older age female groups); aging seemed to be associated with increases of weight, arm muscle variables and with arm fat accumulation in women and with increases of arm muscle variables in men. The values for anthropometric measurements were in general higher than those found in other Brazilian studies; on the other hand, they approximate to but do not entirely agree with the data representative of the international referential adult population: differences were mainly concerned with body weight and upper arm muscle parameters, which were lower in our sample. As regards energy intake, values found in subjects under 50 years of age were lower than the recommended dietary allowances; averages found for protein intake were above the level recommended by WHO/FAO/UNU (1985). The mean values for serum proteins and lipids were similar to those of referential data. As regards the hypersensitivity tests, it was found that none of the individuals challenged with four antigens (PPD, Candidin, Vaccinia and phytohemagglutinin) presented less than two positive skin reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307422 TI - [Risk of infections by the human immunodeficiency virus (HIV) among health professionals]. AB - To investigate the occupational risk of infection by HIV among health professionals, 36 cases of occupational accidents involving exposure to material potentially infected with HIV, reported at a Brazilian General Hospital (HCFMRP), were studied. Of the injured workers 75% were female and 25% male (ranging from 23 to 49 years old) and just one of them had high-risk behavior of HIV infection. Of these health professionals, 52.8% were nursing auxiliaries, 19.4%, nurses, 13.9%, nursing attendants, 5.5%, laboratory technicians, 2.8% surgery instrumentalist, 2.8% accountants and 2.8% nursing technicians. In 47.2% of cases the workers had a parenteral exposure to blood (needlestick injuries). The right hand and fingers were the body areas most effected. The serologic test to detect HIV antibodies by the ELISA method was required of all the workers. The results were negative and no seroconversion was registered during the one year follow-up period. The professionals were retested one month, 2 months, 6 months and one year after the exposure. In conclusion, the risk of infection by HIV among health professionals of HCFMRP seems to be very low. Continuing education should be provided for health care workers with a view to reinforcing the use of universal precaution, especially those to prevent injuries caused by needles or other sharp instruments. PMID- 1307423 TI - [Presence of Aedes (Stegomyia) albopictus (Skuse) in the city of Sao Paulo, SP, Brazil]. PMID- 1307424 TI - [Accuracy of risk indicators of the Infant Life Defense Program in a region of the Sao Paulo State, Brazil]. AB - The Infant Life Defense Program of Health Department of Bauru City SP, Brazil, has diagnostic criteria for the inclusion of newborns. The diagnostic criteria combine eleven social and clinical indices of infant mortality risk, defined by in the light of a review of the literature and previous case studies. The indices are easily collected at the hospitals during delivery. The objective of this study is to propose an alternative diagnostic criteria, using the same social and clinical indices, of greater sensitivity and same proportion of children included in the program. The data on the newborns were collected between May 11, 1986 and November 10, 1987. The mortality period was defined as between 7 days and 6 months, which was the follow-up period for the infants enrolled in the program. The method of analysis was the determination for each index of the crude relative risk in a univariate analysis and the adjusted relative risk using the logistic regression procedure. A score system was constructed on the basis of the sum of the excess risk of each index. PMID- 1307425 TI - [Microhabitats of Aedes albopictus (Skuse) in the region of the Paraiba Valley, Sao Paulo State, Brazil]. AB - The objective of this study was the determination of extent of the spatial distribution of Aedes albopictus in the Paraiba River Valley, State S. Paulo, Brazil. Thus, collections of larvae and pupae mosquitoes were carried out at six sites distributed along a transection with a 10-km extension. The target was the tree-holes but artificial containers were also used in this investigation. Aedes terrens and Ae. albopictus were the only species of genus Aedes present in the tree-holes mentioned. The segregation of seven species of the tree-hole community was undertaken in the light of macrohabitat and microhabitat features. Thus, the distribution of Ae. albopictus was found to cover the rural, rural-urban and urban zones, but the rural-urban held the preference. Ae. albopictus never present in the residual and primary forest. The favorable factor to infestation with Ae. albopictus in the Paraiba Valley seems to have been the large number of natural niches made vacant by human influence. The rain has been important in the production of larvae and pupae, but the rainfall period does not coincide with the maximum production on them. The tree-holes whose volume exceeded 600 ml were the most productive breeding places. The abundance of these two stages occurs in the summer and autumn. However, the highest peak was observed in the months of March and April. These seasonal variations were found to be common in both the bamboo trap and the artificial container. The temperature data suggest a limit of from 17 to 23 degrees C for the best development of larvae. In the light of this, the strain of Ae. albopictus studied seems to have originated in tropical Asia. Just as happened with Ae. aegypti it may become an important epidemiological vector for the dengue fever and provide links for yellow fever transmission in Brazil. PMID- 1307426 TI - [Prevalence of serological markers of hepatitis B in a small rural community of Sao Paulo State, Brazil]. AB - Prevalence of three hepatitis B markers was measured by immunoassay techniques in small rural community of the State of S. Paulo, Brazil. Total prevalence was 7.74%, corresponding to values of 0.10%, 1.69% and 7.74% for HBsAg, anti-HBs and anti-HBc, respectively. The importance of anti-HBc determination in such studies is stressed. Comparisons between the low viral circulation observed in this area and high prevalences described in other rural communities may contribute to the raising of new hypothesis concerning alternative transmission mechanisms of hepatitis B. PMID- 1307428 TI - [The model of state health policy and the system of medical assistance adopted in present-day Brazil]. AB - A contribution to the analysis of the health reform presently occurring in Brazil is presented. The need to consolidate the theoretical background which supports the advances already achieved in order to understand recent events in the area is stressed. In this regard, the health reform is understood as a question transcending the mere administrative and managerial aspect of the health system, since it necessarily involves a redefinition of the concepts of health, disease and the medical practice adopted by the dominant mechanistic paradigm of medicine. The recent events which delineate the health system in Brazil are analysed and criticised in the light of this concern. PMID- 1307427 TI - [Susceptibility tests of the bedbug, Cimex lectularius L. (Hemiptera, Cimicidae) to DDT in Belo Horizonte, MG (Brazil)]. AB - Susceptibility levels for the adult bed-bug, Cimex lectularius, in Belo Horizonte, Minas Gerais-Brazil, to DDT, were determined during the period 1985 to 1986. The test results showed that a 4% dosage of DDT is not enough to kill 55% of the insects. The data are sufficient to show that there exists bed-bug resistance to DDT in Belo Horizonte. PMID- 1307429 TI - [Mortality due to Chagas disease in Sao Paulo State (Brazil): subsidy for the planning of chagasic patient care]. AB - In order to estimate the size of the population with Chagas' disease, an essential parameter for the establishment of an adequate health care policy for this group of patients, data from 1,646 death certificates from the "Fundacao Sistema Estadual de Analises de Dados" in which Chagas' disease was mentioned in the State of S. Paulo in 1987 were examined. The population under study comprised adults between 15 and 70 years of age. Objectives also included the determination of Proportional Mortality, Potentially Lost Years of Life and regional distribution of the events in the counties of the State of S. Paulo. Chagas disease accounted for 0.9% of the totality of the causes of death, Proportional Mortality was 1.2% and the proportional participation of Chagas' disease in the Potentially Lost Years of Life was 1.1%. Corresponding data for Ischemic Heart Disease were, 4.0% and 1.2%. 20.8% of the deaths occurred in counties other than the county of residence, the indexes of evasion varying from 17.8% to 29.1% for different regions. Males (22.8%) more often than females (17.4%) died outside their county of residence. The largest number of deaths occurred in the metropolitan area of S. Paulo, although Ribeirao Preto county presented the highest mortality indexes. PMID- 1307430 TI - [Evaluation of epidemiologic surveillance practice in the public health service in Brazil]. AB - The results of a process evaluation of the epidemiological surveillance activities in 948 health units, situated in 98 of the most populated cities of each State in the country are presented. The survey was conducted towards the end of 1985. The following aspects were analyzed: information system, data analysis, epidemiological investigation. Institutional insertion, vaccination activities, management aspects and capacitation of the health worker were considered as potential determinants of performance. Data were submitted to correspondence analysis and a process of ascendant hierarchical classification, using the statistical package "Systeme Portable Pour L' Analise de Donnees-SPAD". The performance pattern was not found to be homogeneous. Six different classes of epidemiological surveillance practice in the health units were observed. In 53.7% of the services visited, even the most elementary norms of activity were not complied with. The presence of vaccination activities in the health units was associated with better performance in epidemiological surveillance. The study points to the need to review the epidemiological surveillance model in use in Brazil. It is no longer acceptable to restrict the practice of epidemiology in health services to communicable diseases, now to manage programs and services without epidemiological information. PMID- 1307431 TI - Hygiene habits and carriers in families with a child who has had typhoid fever. AB - The relationship between asymptomatic shedding of bacterial enteropathogens and the hygiene habits of families who have had a child with typhoid fever (TF) are investigated. The sample was made up of 80 families: 40 families in which one child had had TF (Group A) and 40 in which no children or either of the parents had had a history of TF (Group B). In each group 20 families belonged to a low socioeconomic status (SES) and 20 to a high SES. A structured interview was used to evaluate the SES and the hygiene habits of the child; observations were made to measure the hygiene habits of the family (toilet, kitchen and food preparation) and bacteriological studies (fecal samples and hand markers). Results show that carriers were more frequent in Group A than in Group B. The bacterial species found were significantly more numerous in Group A than in Group B (fecal samples: E. coli, the classic serotypes, Shigella ssp, and hand markers: E. coli). Families of Group A had higher carriage rates than those of Group B. Finally there exists a significantly higher association between inadequate hygiene habits and carrier families. These results show the need to teach specific habits of proper hygiene to the entire population, because the fact of belonging to the high SES does not in itself preclude inadequate hygiene habits. PMID- 1307432 TI - Health and poverty: health management by the woman. AB - The goal this follow-up study was to relate the mother's marital satisfaction to family health status in a low SES. The random sample was made up of 30 families with children under 7 years old: 15 considered as sick (Group A) and 15 as healthy (Group B). Both group had similar demographic characteristics (age of father and mother, persons per family group and age of children) and SES. Results showed that mothers were those mainly in charge of their family groups. Mothers of Group A were significantly less understanding and more dissatisfied than those of Group B (p < .05 and p < .01). Mothers of Group A had significantly more arguments with their partners than those of Group B (p < .006). Health care was learned less from the child's own mother in group A than in B (p < .05). Health was considered by mothers of Group A as something that "must be taken care of" more than by those of Group B p < .01). The behaviours of mothers in choosing one of the health systems was similar in both groups. Dissatisfied mothers were associated more with sick family members during the 6 month follow-up. It is suggested that the satisfaction of the mother is a factor that needs further investigation because health is managed by mothers is the large majority of families. PMID- 1307433 TI - [The prevalence of iron deficiency in pregnant women at their first consultation in health centers in a metropolitan area, Brazil. Etiology of anemia]. AB - Three hundred and sixty-three pregnant women enrolled in the Pregnancy Medical Care Program of S. Paulo Health Department in the district of Butantan, S. Paulo city, Brazil, were studied at their first routine consultation between April and October, 1988. Their average age was 25 and 65.9% of them belonged to families with a monthly income below US$50.00 per capita. Only 3.1% presented an income above US$150.00 per capita. Taking the minimum transferrin saturation threshold of 15% as determining iron deficiency, a 4.6% prevalence of iron deficiency was observed in the first trimester, 17.3% in the second trimester and 42.8% in the third trimester, resulting in an overall prevalence of 12.4%. There was no significant difference between prevalences of iron deficiency according to the number of pregnancies. The prevalence of iron deficiency was higher in women presenting incomes below US$50.00 per capita. PMID- 1307434 TI - [Risk estimates of tuberculosis infection in BCG-vaccinated populations]. AB - The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a natural infection. So revaccination in this population should indicate the group infected by the Koch bacilli. To assess the applicability of these assumptions in estimating the risk of tuberculosis infection in regions with high BCG coverage a study was undertaken on schoolchildren between 6 and 9 years of age who were attending the municipal schools in the east zone of S. Paulo City, in the course of the first semester of 1988. Of 11,455 who were vaccinated only 7,470 were tested with PPD, revaccinated and retested ten weeks later; 3,314 of these were vaccinated in the first trimester of life with a half dose and 4,156 received a full dose at later ages (75% during the first year, 20% during the second and 5% during the third). In comparing the results pre and post vaccination by correlation table, the calculation of infection was made according to the criteria of the original method and to the modifications made by the authors under separate cover for those vaccinated in the first trimester and those vaccinated later. The risk of infection was 0.35% and 0.37%, respectively, for the original model and 0.45% and 0.49% for the modified model. The referential was 0.55%. The difference between model and age or with the referential was not significant (p > 0.005). Data suggest that the method is applicable to estimate the risk of tuberculosis infection in schoolchildren vaccinated with a full dose of BCG during the first year of life. PMID- 1307435 TI - Data for the properties of Listeria strains (a review). AB - It seems that taxonomy of listeriae is in a fluid stage. Between beta-haemolytic property and virulence of these bacteria a strong relationship has been demonstrated. These characters are coded by hlyA gene which seems to belong to a monocistronic unit. Virulent Listeria strains possess specific surface antigens and can enter as well as multiply in host cells. Their exact human virulence is not known. Listeriae can grow from around 0 to 42 degrees C and can survive either the effect of frost or of temperature of 48 degrees C. They may form biofilm on different surfaces. Their growth kinetics, persistance and heat resistance can be influenced by many factors (type of growth environment, pH, acidulants, salts, chemicals, antibiotics, plant substances, enzymes, humidity, atmosphere, temperature, prior temperature-effects, microbial competition and the length of influences). Radiation sensitivity of Listeria is usual. Plasmid mediated antibiotic resistant mutant of Listeria monocytogenes is verified. PMID- 1307436 TI - Colonization of infant mice with flagellar variants of Campylobacter jejuni. AB - The role of flagella in the colonization of the intestine by Campylobacter jejuni was investigated by challenging infant mice with two flagellated strains and their nonflagellated variants. The intestinal tracts of infant mice were regularly colonized with motile strains, but not by nonmotile variants. Colonization of mice with motile C. jejuni occurred with as few as 1000 bacteria per mouse. PMID- 1307437 TI - Impact of weather changes on the growth of the unicellular Blepharisma undulans (Stein). AB - The growth of Blepharisma undulans (Stein) cells durably treated and not treated with insulin was followed up for three months with special regard a possible impact of meteorological factors on the growth rate. The growth rate of the protozoon was not appreciably altered by weather changes but the growth curves for cells treated and not treated with insulin indicated opposing trends of multiplication under the influence of approaching weather fronts. Warm fronts which have a parasympathic effect and cold fronts which have a sympathetic effect uniformly enhanced the growth rate of the untreated cells and retarded that of the insulin treated cells. PMID- 1307438 TI - The effect of kanamycin treatment of rats on the development of gastro-intestinal syndrome of radiation disease. AB - Kanamycin pretreatment through stomach tube eliminates the endotoxin producing Gram-negative bacteria of the intestinal flora and can delay the death of rats suffering from gastro-intestinal syndrome of radiation disease. Endotoxins probably play a significant role in the pathological process of the syndrome. PMID- 1307440 TI - Modified spot hybridization test using biotinylated DNA probe. AB - A modification that simplifies the spot hybridization technique is described for using biotinylated DNA probes. Plasmid EWD299 having LT gene insert, labelled with biotin either by nick translation or using photobiotin was used as DNA probe for the specific detection of enterotoxigenic Escherichia coli. A simple protocol has been described for easy lysis of test samples by boiling in distilled water followed by detergent treatment and was found to be as efficient as the lysis using lysozyme and protease. Three different solid supports namely DEAE-cellulose paper, nitrocellulose paper and nylon membrane were also compared for their suitability in this spot hybridization test. Nitrocellulose paper was found to give better colour signal with the photobiotinylated DNA probe. PMID- 1307439 TI - Multiple enlargements in the right inverted terminal repeat of the DNA of canine adenovirus type 2. AB - The Manhattan strain of canine adenovirus type 2 (CAV 2) was examined. Restriction endonuclease analysis and blot hybridization experiments revealed the heterogeneity of the viral DNA. At least 9 unequally expanded species of the viral genome have been recognized. This diversity is caused by different enlargements in the right inverted terminal repeat (ITR) of the virus. The differences between the individual enlargements were shown to be the different multiples of 150 base pairs. Relatedness of CAV 2 DNA to the DNA of bovine adenovirus type 2 (BAV 2) and human adenovirus type 2 (HAV 2) has also been observed during DNA hybridization experiments. PMID- 1307441 TI - Distribution of aflatoxin-producing moulds and aflatoxins in dairy cattle feed and raw milk. AB - Distribution of aflatoxigenic moulds and aflatoxin B1 in Yugoslav dairy cattle feeds as well as the presence of aflatoxin B1 and M1 in raw milk, was tested. The experiments were carried out through three years (in all seasons). Samples were taken from state and private farms in Vojvodina. Feeds were contaminated in 83 100% with moulds. Fungi of farms in Vojvodina. Feeds were contaminated in 83-100% with moulds. Fungi of Aspergillus flavus-oryzae group were present permanently and the highest incidence of them was noticed during the third research year. Aflatoxin B1 was not found in the first year, but malt spent grains used for cows' feeding in summer of the second research year was contaminated with it (50.0 micrograms/kg). The same feed and pelleted sugar beet pulp were contaminated with aflatoxin B1 in winter, spring and summer of the third research year (5.0 to 16.0 micrograms/kg). Aflatoxin B1 and M1 were not found in raw milk through three-years investigations. PMID- 1307442 TI - Production and regulation of a thermostable protease by Pseudomonas sp. B45. AB - A Pseudomonas sp. produced an extracellular thermostable protease which required induction by peptone. Growth of the organism and the production of protease was optimum at 30 degrees C. The enzyme was subjected to catabolite repression by glucose. Both chloramphenicol and rifamycin completely abolished protease production indicating de novo synthesis of the enzyme. Leucine, lysine, histidine and glycine enhanced the protease production considerably and they were the most effective when added during the active period of production. Glucose repression could not be relieved by addition of leucine. PMID- 1307443 TI - A 4-kilobase congo red binding plasmid DNA fragment of Shigella dysenteriae 1 suppresses the growth and cell differentiation in Escherichia coli. AB - A 4-kilobase congo red binding plasmid DNA fragment of pCAT 120 of Shigella dysenteriae 1 was transferred to an Escherichia coli K12 strain by transformation. Transformants were unable to grow in any liquid broth medium. Electron microscopic studies revealed that the transformants grown on tryptic soy agar were associated in clusters after cell division. Normal cell separation among the transformants in comparison with recipient E. coli K12 was only observed when the growth medium was supplemented with sterile culture filtrate of the recipient strain. An unknown factor(s) required for cell separation located on the chromosome was suppressed by a 4-kb congo red binding plasmid DNA (pCAT 120) fragment of S. dysenteriae 1. PMID- 1307444 TI - [Carotid body tumors: the clinical, diagnostic and therapeutic aspects]. AB - The authors discuss the epidemiology, histology, symptomatology, diagnosis and therapy of carotid body tumors, basing their discussion on three personal observations and on a case of cervical dermatocyst which showed clinical and radiological data consistent with diagnosis of a glomus tumor. Chemodectomas of the neck are more often seen in the carotid body and are considered histologically benign, although they might induce local or distant metastases. Clinical presentation is often non-specific and may only consist in a slowly growing mass in the higher jugular-carotid region. Among the various imaging techniques (CT, MR), supra-aortic selective angiography, including digital subtraction techniques, is now considered the most reliable tool, while ultrasonography and gammagraphy with 99mTc-gluconate or 131I-MBG are recommended for screening and family testing purposes. Biopsy is to be avoided as it is very likely to cause massive bleeding and because of the high percentage of false negatives. Surgery is the choice treatment, and lateral cervicotomy is the recommended approach for exeresis of the mass, while radiotherapy should be planned in patients with precise contra-indications for surgery and when the tumor mass has already reached the skull base. Pre-operatory selective embolization is still controversial. PMID- 1307445 TI - [Experimental perilymphatic fistula: the electrocochleographic findings]. AB - The aim of the present study was to evaluate the effect of experimental perilymphatic fistula on cochlear electrophysiological responses. Six albino guinea pigs, in which recording electrodes were implanted in order to record the electrocochleogram, were used. Experimental protocol investigated cochlear responses before the induction of the fistula in the round window membrane perforation and then two month later. Compound action potential thresholds increased immediately after perforation of the round window membrane. The thresholds rapidly recovered. This phenomenon was accompanied by clear-Out reduction in amplitude upon suprathreshold stimulation. This latter observation associated with a decrease in the amplitude of the threshold seems to be a specific audiologic sign of the fistula. The clinical implication are discussed. PMID- 1307446 TI - [The measurement of cochlear flow by laser Doppler in man: the preliminary results]. AB - Laser-Doppler flowmetry is presently one of the methods of choice in measuring cochlear blood flow. The techniques is non-invasive and is based on the frequency shift of the laser beam induced by the red blood cell movement. Previous studies of cochlear blood flow carried out on animals and humans demonstrated the reliability of laser-Doppler flowmetry and its usefulness in understanding inner ear microcirculation physiology. In this paper we present preliminary data obtained from three patients examined under general anesthesia while undergoing tympanoplasty. Results showed that tracings, whose baseline is proportional with the blood flow, are characterized by waves correlated to pulse beat and automatic ventilation. Moreover, intrinsic contractions of inner ear vessels (waves of vasomotion) as exist in cerebral microcirculation, were observed. Pharmacological hypotension hypocapnia and the application of epinephryne determine a significant reduction of cochlear blood flow. These results suggest that while cochlear blood flow is related to systemic pressure, it has an intrinsic control system. As well since we did not obtain any modification in bone conduction threshold after surgery, we conclude that laser-Doppler flowmetry is a safe technique. PMID- 1307447 TI - [Orbital and endocranial complications in acute sinusitis in childhood]. AB - Acute infection the paranasal sinus is a rather frequent pathology in children. On the contrary, local orbital complications are rare. The employment of antibiotics reduces the incidence of complications but can sometimes conceal their appearance so that diagnosis is delayed. Orbital as well as intracranial complications of ethmoidal and maxillary sinusitis are most often encountered in childhood. Within a brief time span, 8 patients with complicated frontal and ethmoid-maxillary sinusitis were diagnosed and treated: 4 cases of periorbital cellulitis, 2 of subperiorbital abscess and 2 of orbital abscess (one of which with cavernous sinus thrombosis). Particularly relevant from the diagnostic point of view was the employment of C.T. scan which furnished an accurate definition of the orbit and its surrounding structures which influenced treatment choice. Under antibiotic cover all patients but one (who had been treated very early and had responded immediately to intensive antibiotic therapy) were treated surgically and the clinical course of the disease showed significant improvement very shortly after surgical drainage. PMID- 1307448 TI - [The treatment of nasal polyposis with the neodymium-YAG laser]. AB - Recurrent nasal polyposis is one of the most common problem in clinical rhinology. The authors describe the anatomic and functional results obtained by Nd:Yag laser procedures performed on 47 patients, with recurrent polyposis. The use of Nd:Yag laser under local anaesthesia, by means of a rigid fiberscope, permitted to obtain a well limited excision of the pathological tissue with respect of nasal physiology. At the end no nasal packing was used because unnecessary. The authors explain the details of the method and the results obtained, pointing out this well tolerated treatment, even when repeated, taking care, in the same time, the different pathogenesis of disease. PMID- 1307449 TI - [Invasive nasosinusal aspergillosis in an immunocompetent patient]. AB - The authors describe a case of invasive nasosinusal aspergillosis in an immunocompetent patient. After a careful bibliographic review, they emphasize that in the present case the diagnosis was made by means of fungal culture as the clinical picture, imaging techniques and histopathological findings were aspecific. The pathogenetic agent resulted Aspergillus tamarii which belongs to the Aspergillus flavus group and is one of the most unusual agents in literature. The treatment of choice, in the invasive form, is surgery that should be as radical as possible followed by a medical therapy. In the present case, after two phase radical surgery on all the paranasal sinuses, medical treatment with traconazole was employed with excellent local results at a follow-up of one year. PMID- 1307450 TI - [Adenotonsillectomy: the evaluation of the long-term results after more than 7 years from the intervention]. AB - A study was carried out on 110 patients with various diseases related to chronic inflammation of the tonsils and to hypertrophic adenoids. Sixty-two of these patients underwent adenotonsillectomy, while the others were followed clinically and, where necessary, given medical treatment. At the first observation the patients were between the ages of 2 and 12 (mean age 6.1 years). At the start of the present study the patients ages ranged from 10 to 22 (mean age 17 years). Clinical follow-up was carried out on the patients 2 and 7 years after the first observation and/or adenotonsillectomy. The patients were divided into homogeneous groups according to the severity of symptoms. The A.A. evaluated changes of the following clinical parameters: annual frequency of inflammatory pharyngotonsillar episodes, nasal respiratory obstruction, sore throat, otologic pathology. Evaluations were carried out statistically in each group. After more than 7 years from surgery, the significant reduction of various diseases related to chronic inflammation of the tonsils and to hypertrophic adenoids, in accordance with the findings after 2 years from surgery, underline the effectiveness of adenotonsillectomy in correctly selected candidates. PMID- 1307451 TI - ["How the Americans judged us" (ORL and the Military Medical Corps during the Great War)]. PMID- 1307452 TI - [Ethical problems in tumors of the head and neck]. PMID- 1307453 TI - [Mitral valve replacement with porcine bioprosthesis in children. Evaluation of 29 patients during 12 years]. AB - PURPOSE: To analyze the clinical result of the mitral valve substitution for the porcine bioprostheses, the incidence of dysfunction caused by calcification and its importance related to the durability of bioprostheses and also the patients' survival. METHODS: Twenty-nine children of about seven to sixteen years old were operated on from November 1977 to August 1982 and all of them received porcine bioprostheses of low profile. RESULTS: There were three (10.34%) hospital deaths and nine other late mortalities. The follow-up period varied from 4 to 128 months with average of 58.17 months and with the loss of nine patients. An actuarial survival rate of 46.08% has been observed at 11 years after surgery. Calcification of 21 bioprostheses occurred in 14 out of 17 follow-up patients; 47.6% of them happened until the third year of pos-operative and 85.7% until the fifth year. Eleven patients were reoperated on with 9.09% of hospital mortality. There were no cases of thromboembolism. CONCLUSION: Porcine bioprostheses works well with an evident clinical improvement of patients, with no thromboembolic accidents. However, its durability has been affected by the high incidence of calcification, which is responsible for an increase in late morbidity and mortality. Mitral valve disease treatment in children must be conservative, in an attempt to solve the problem with the different available plastic technics and leave the valve substitution to be a last option. In that case, the preference is given to the homologous bioprostheses. PMID- 1307454 TI - [Analysis of fever in 58 cases of infective endocarditis]. AB - PURPOSE: To evaluate if fever is an objective criterion in the assessment of response to antibiotic therapy and in the prognosis of patients undergoing treatment for infective endocarditis (IE). METHODS: Fifty-eight cases of IE, occurring from January 1980 to December 1989 have been analysed retrospectively in this study. Emphasis was given to the clinical history and body temperature changes during the first five weeks of treatment. Patients were divided in three groups according to the number of febrile peaks per week. Temperature was assessed weekly from each patient's highest peak weighed average. RESULTS: At the first exam, 52 patients (86.2%) presented fever. All patients had at least one episode of fever during their hospitalization. There seemed to be a relation between the number of febrile peaks during a one week period and the mean body temperature, so that these patients who presented four or more peaks in a week had a higher mean body temperature than those with two or less febrile peaks during the week. After the second week of treatment, patients with two or less febrile peaks had a 93.1% survival and average of 35.5 days of hospitalization, whereas those with three or more febrile peaks had 63.6% survival and an average of 47.5 days of hospitalization. CONCLUSION: The results of this study show that the intensity of fever is linked to the number of febrile peaks per week, regardless to treatment duration. Should there be three or more febrile peaks weekly after the second week of treatment, therapeutic strategy should be reviewed, considering even surgical treatment. In many cases, the persistence of fever represented the clinical expression of complications which determined a higher mortality rate and a longer hospitalization. PMID- 1307455 TI - [Myocardial infarction as a consequence of infective endocarditis in valvar bioprosthesis]. AB - A sixteen year-old male, followed in the Unicamp Cardiology Clinic with a previous record of rheumatic heart disease and a biological mitral prosthesis, presented with infective endocarditis. In spite of a good initial response to antibiotic therapy, the patient died in two weeks. Autopsy disclosed endocarditis of the prosthetic valve and embolic occlusion of the circumflex branch of left coronary artery. PMID- 1307456 TI - [Tachycardiomyopathy induced by atrial fibrillation]. AB - A 56 year old woman with a previously normal heart developed severe left ventricular dilation and hypo-contractility after a few weeks of a refractory, high ventricular rate atrial fibrillation. Reduction of heart rate with verapamil resulted in a rapid normalization of myocardial contractility. PMID- 1307457 TI - [Functional atresia of the pulmonary valve]. AB - Three newborn children with cyanosis due to Ebstein's anomaly of tricuspid valve with an important hemodynamic repercussion presented features of imperforation of pulmonary valve. On the follow-up, clinical and laboratory findings verified that pulmonary atresia was functional resulting from a combination of low right ventricular pressure and high pulmonary vascular resistance. PMID- 1307458 TI - [Post infarction ventricular septal defect. Echocardiographic analysis of patients treated with positive end-expiratory pressure]. AB - Interventricular septal rupture is a life-threatening complication occurring in 0.5 to 1.0% of patients following acute myocardial infarction and often results in right and left ventricular failure. This study aimed at evaluating the echocardiographic effects of PEEP on right (RV) and left (LV) ventricular dimension in three patients who developed a postinfarction septal defect and in whom acute respiratory failure was a preterminal event. The effects of PEPP on the heart remain controversial. We observed in all three patients a sudden large increase in RV dimensions and hence, probably through ventricular interdependence, a proportional decrease in LV dimensions. The progressive leftward septal displacement with increasing levels of PEEP probably contributed to reduce LV compliance. We concluded that PEEP therapy in this group of patients had no proven beneficial effects and probably contributed to further RV dilatation and failure. PMID- 1307459 TI - [Insulin resistance syndrome. I]. PMID- 1307460 TI - [Transdermal nitroglycerin in patients with stable angina]. AB - PURPOSE: To evaluate the nitroglycerin patches efficacy and tolerability in patients with stable angina pectoris. METHODS: One thousand and five hundred and thirty nine patients with stable angina pectoris, mean age 61.0 +/- 10.3, 891 men and 648 women were prospectively evaluated by five hundred and thirty five specialists after 5 mg or, posteriorly, if clinical necessary, 10 mg of nitroglycerin patches during 12 weeks. Clinical evaluation, electrocardiogram (ECG) and treadmill exercise were obtained on study entry and at weeks 2, 4, 8 and 12 for clinical evaluation, and at week 12 for ECG and treadmill exercise. RESULTS: A significative reduction was observed in the number of angina crisis, sublingual nitrates consumption, arterial blood pressure and on the percentage of positive treadmill exercise tests. The heart rate and nitroglycerin patches dose did not show statistical differences. The compliance of transdermal administration was excellent. CONCLUSION: The nitroglycerin patches administration was effective for stable angina pectoris with excellent patient's compliance. PMID- 1307462 TI - [Fever and infective endocarditis]. PMID- 1307463 TI - [Management of newborn infants with heart disease--current status and the necessary reformulation]. PMID- 1307461 TI - [Myocardial ischemia with stable angina pectoris: clinico-ergometric evaluation after the use of diltiazem]. AB - PURPOSE: To evaluate the efficacy of diltiazem versus placebo in patients with stable angina. METHODS: Eight-seven angina pectoris patients, mean age of 57 +/- 9, 82 white and 79 male were evaluated in a randomized, double-blind trial of two groups of patients diltiazem and placebo, 3 to 4 tablets a day (diltiazem 180 to 240 mg daily). The patients were evaluated after laboratory tests and clinical ergometric examinations. A coronary arteriography was performed on study entry. RESULTS: The average of anginal attacks, number of weekly sublingual nitrate, heart rate, systolic and diastolic pressure at rest and at the end of diltiazem period were significantly lower (p < 0.05) regarding same periods on placebo. The percentage of depression for ST-segment was lower for diltiazem when compared with placebo (p < 0.05) and the percentage of patients that reach higher stages in the ergometric test was significantly better for diltiazem. Heart rate and systolic plus diastolic pressures after exercise did not differ in both groups. CONCLUSION: Diltiazem reduced the clinical and electrocardiographical aspects and raises the effort tolerance during the ergometric test in patients with stable angina. PMID- 1307464 TI - [Pathogenesis of mitral valve prolapse in patients with chronic Chagas disease: study of papillary muscle myocarditis]. AB - PURPOSE: Studying the mitral valve in chronic Chagas' heart disease, searching a possible cause effect relationship between this condition and valve prolapse. METHODS: Seventeen hearts were surveyed from individuals exhibiting chronic chagasic cardiopathy, 11 males and 6 females, aged between 31-84 (average 54) years. The hearts came from necropsies carried out until a year before. Properly preserved samples were analyzed macro and microscopically. Fragments were excised from the mitral valve papillary muscles, anterior, lateral and posterior regions of the left ventricle, interventricular septum, free wall of right ventricle and atrium walls. RESULTS: Chronic myocarditis was found ill all the samples (mild in 6 of them, moderate in 7 and severe in 4). Also, the papillary muscles exhibited myocarditis in all of the samples, and in 15 of them the degree of severity was equal to or superior than the observed in degree other regions of the heart. CONCLUSION: The chronic chagasic cardiopathy, the papillary muscle constitute a frequent site of myocarditis. This fact must be held in mind when one discusses the pathogenesis of the prolapse of the valve. PMID- 1307465 TI - [Acute aortic dissections. Hospital outcome of 186 cases]. AB - PURPOSE: To determine in hospital outcome acute aortic dissection patients. METHODS: We revised 186 consecutive cases (up to 14 days of dissection), in a period of 6 years. The patients were divided according to Daily's classification (types A and B). RESULTS: Type A--127 cases: a) 75 were surgically treated (37 died); b) 2 were medically treated (both died); c) 39 died before the definitive treatment could be initiated; d) 11 died misdiagnosed or undiagnosed. The total mortality was 70.0%. Type B--59 cases: a) 11 complicated cases were surgically treated (6 died); b) 40 were medically treated (8 died); c) 7 died before the definitive treatment could be initiated; d) one died misdiagnosed. The total mortality was 37.25%. In summary, 41.4% of the patients survived. 28.4% died despite the definitive treatment, 24.7% died before the definitive treatment could be initiated and 6.4% died without the correct diagnosis. CONCLUSION: The acute aortic dissection is a dramatic situation, mainly type A. In this type of dissection many patients (41%) died misdiagnosed, undiagnosed or without enough time to surgical therapy. So, an earlier diagnosis and treatment are imperative. PMID- 1307466 TI - [Spontaneous intraparenchymatous hematomas. Experience with 134 cases]. AB - One hundred thirty four cases of spontaneous intraparenchymatous hematomas have been studied. They were separated into six groups according to criteria related to topography, level of consciousness, and hematoma volume. Treatment protocols- conservative, conservative with I.C.P. monitoring, and surgical--were different in each group. Results have shown an increased mortality (p < 0.05) among patients whose level of consciousness were more severely compromised, in those older than 50 years old, and in those harbouring quadrilateral, intraventricular or brainstem hematomas. Overall mortality was 26.1%. PMID- 1307467 TI - [Isolated vasculitis of the central nervous system and involvement of the 8th cranial nerve: rare manifestations of acquired immunodeficiency syndrome]. AB - The authors report the case of an AIDS patient with rare neurologic manifestations: primary vasculitis of the central nervous system and VIII cranial nerve dysfunction. The authors make a review on the subject, and call special attention for the differential diagnosis. In fact, the patient, a 36 year old woman, with promiscuous life, presented with dizziness, gait ataxia, nausea, headache and hypoacusia. Seven days after the admission, she noted blurred vision in both eyes and soon she became blind. The physical examination showed bilateral optic neuritis and vestibulocochlear dysfunction, stiff neck and fever. No abnormalities were detected on CT scan. CSF showed 40 mononuclear cells/mm3, 79 mg/dl of proteins and normal glucose content. Microbiological research was negative. Serum anti-HIV test was positive. The hypothesis of primary CNS vasculitis was made, and pulse methylprednisolone therapy was introduced with good recovery of neurological syndrome except for persistent amaurosis. PMID- 1307468 TI - [Invasive aspergillosis of the sphenoid sinus and paralysis of the 6th nerve]. AB - A case of aspergillosis of the sphenoid sinus manifested as an isolated sixth nerve palsy occurred in a 74-year old diabetic woman who had no complaints of headache or symptoms suggestive of sinusitis. A CT scan demonstrated a large mass occupying the sphenoid and ethmoid sinuses extending posteriorly to the clivus. There was a calcific density within the opacified sinus and bony erosion of the sphenoid walls and the sella turcica. The patient underwent a sublabial transseptal sphenoidotomy with removal of necrotic material and debridement of the surrounding tissue. Histologic examination revealed granulation tissue with chronic inflammatory cells and abundant dichotomously branching hyphae. Postoperatively the patient was given amphotericin B and 5-fluorocytosine. Three months later the sixth nerve palsy had completely cleared and the patient had no other complaint. Sphenoid sinus aspergillosis is a rare disease and may have variable clinical manifestations according to involvement of different structures located closely to the sinus. Our patient developed an isolated sixth nerve palsy which was at onset considered to be caused by diabetes. Computerized tomography scans disclosed abnormalities strongly indicative of invasive aspergillosis. It illustrates the need of appropriate work-up in cases of an isolated sixth nerve palsy even in patients with diabetes or other risk factors. PMID- 1307469 TI - [Acute cerebellar infarction simulating posterior fossa tumor]. AB - We report a case of space-occupying infarction of the left cerebellar hemisphere with occlusive hydrocephalus and left to right shift of the fourth ventricle. The patient, a 58 years old man, underwent shunting and decompressive craniectomy of the posterior fossa and survived without neurological deficits. PMID- 1307470 TI - An association of central post-stroke pain and thalamic hand. AB - Thalamic hand is one of the clinical expressions of the painful thalamic syndrome. This paper relates on a case of a patient with a syndrome of central post-stroke and supra-thalamic pain who also presents a thalamic hand. The authors emphasize the notion that in the syndrome of central post-stroke pain a direct or indirect (infra or supra)-thalamic lesion seems to be an essential element for the genesis of central pain. PMID- 1307471 TI - [Iatrogeny. The importance of clinical diagnosis. Myopathies induced by clofibrate]. AB - The authors describe the neurological manifestations of a female patient with hypercholesterolemia who developed myopathy in the course of her treatment with clofibrate. After the drug was tapered off, the neurological signs and symptoms disappeared. Therefore, attention is called for the importance of the differential diagnosis of iatrogenic myopathies with polymyositis. PMID- 1307472 TI - [In memoriam: Walter Edgard Maffei (1905-1991)]. PMID- 1307473 TI - [Multiple intracranial aneurysms]. AB - Thirty eight patients with multiple intracranial aneurysms were studied. They correspond to 19.4% of all aneurysms treated over a twelve year period in the Servidores do Estado Hospital. 89 aneurysms and 4 infundibuli were detected. In 71.0% of the patients, two aneurysms were found; in 18.4%, three aneurysms; and in 10.4%, 4 or 5 aneurysms were observed. Twenty-seven patients were women and 11 men, ranging in age from 16 to 72 (average 47 years old). Subarachnoid hemorrhage was found in 36 patients (86.8%). The operative mortality in this series was 3.5%. We concluded that patients with multiple intracranial aneurysms should have all aneurysms, that can bleed, clipped through standard micro-neurosurgery technics. PMID- 1307474 TI - Cognitive functions, epileptic syndromes and antiepileptic drugs. AB - Cognitive function of patients on monotherapy specific for their epileptic syndrome has been studied infrequently. We evaluated 7 patients with symptomatic localised epilepsies (SEL) on phenytoin aged 30 +/- 12 (mean +/- standard deviation) years, 8 with idiopathic generalised epilepsies on sodium valproate aged 18 +/- 4 years, 16 with SEL on carbamazepine aged 28 +/- 11 years, and 35 healthy controls aged 27 +/- 11 years. All subjects were of normal intelligence, educated appropriately to age, and led productive lives in the community. Two of the patients on carbamazepine and one on valproate had less than five partial, absence or myoclonic seizures monthly, the remaining were controlled. Carbamazepine serum concentrations were 12 +/- 5 micrograms/ml, phenytoin were 23 +/- 7, and valproate were 62 +/- 23 (mean +/- sd). Tests included immediate recall and recognition for pictures, Stroop test, delayed recall and recognition of pictures. Patients on phenytoin and valproate performed significantly worse than controls on immediate recall, and patients on carbamazepine performed significantly worse than controls in Stroop test (p < 0.01). The results indicate relatively minor effects of the epileptic syndromes and of phenytoin, carbamazepine and valproate on cognition of patients with controlled epilepsy leading productive lives in the community. We conclude that the cognitive deficit found in chronic epileptic patients on poly-therapeutic drug regimen must be multifactorial, and that future studies need to control for all possible variables in order to achieve meaningful results. PMID- 1307475 TI - Neurological manifestations of malaria. AB - The involvement of the nervous system in malaria is reviewed in this paper. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red cells causing sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes nonspecific, immune-mediated, inflammatory responses with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations remains unexplored, but offers excellent perspectives for research at a clinical as well as experimental level. PMID- 1307476 TI - Seizure recurrence in infants with neonatal convulsions. A follow-up study. AB - Twenty three infants with neonatal seizures were followed prospectively to a mean age of 11 months. Only 2 were pre-term and birth weight ranged from 1700 to 4230 grams, with 17 male and 6 female infants. Hypoxic-ischemic encephalopathy was the most common etiology (82.6%). Focal clonic convulsions were the predominant seizure type, present in 7/16 infants in which the seizure type could be identified. All infants had a neurological examination and EEG, and 18 had a cranial ultrasonography performed at the follow-up. Anticonvulsant medication was discontinued, if follow-up EEG and neurological examination were normal. At the follow-up, seizure recurrence was observed in 7/23 (30%) infants. Abnormal EEG, neurological examination and cranial ultrasonography were statistically correlated with seizure recurrence. We conclude that infants with neonatal seizures can remain free of anticonvulsant medication provided they have normal neurological examination, EEG and cranial ultrasonography. PMID- 1307477 TI - Brain SPECT in the pre-surgical evaluation of epileptic patients. Preliminary results. AB - Pre-surgical evaluation of epileptic patients consists of neurological examination, intensive electroencephalographic (EEG) monitoring and anatomical studies (CT and MRI). Functional methods such as PET and SPECT imaging are now used more frequently. We have studied pre-operatively 15 adult epileptic patients (8 female, 7 male) using a rotational scintillation camera interfaced to a dedicated computer. The tomographic images were obtained 15 minutes after intravenous injection of 99mTc-HMPAO. All had MRI scanning and intensive EEG monitoring which generally included seizure recording. Five patients had progressive lesions (3 meningiomas, 2 astrocytomas). In 10 patients, neuroradiological studies did not show the presence of progressive lesions (2 normal scans and 8 cases with inactive lesions). Two patients with meningioma showed hypoperfusion at the lesion site while the third patient had a marked hyperperfusion which might correlate with the clinical diagnosis of epilepsia partialis continua. In the astrocytoma patients SPECT scans showed hypoperfusion at the lesion site. Data obtained from the 10 patients without progressive CNS lesions showed: (a) in 4, SPECT findings correlated well with the anatomical findings; (b) in 5 instances, SPECT was able to disclose additional functional deficits; (c) in one case, there was no SPECT correlate of a discrete anatomical lesion. In 5 of these cases with no progressive lesions (n = 10) SPECT findings were useful as a complementary tool in determining the clinical or surgical management of these patients. Despite the small number and heterogenicity of the present sample, SPECT seems to be an useful tool as part of the clinical workup of epileptic patients who are candidates for epilepsy surgery. PMID- 1307478 TI - Effects of stimulation intensity, gender and handedness upon auditory evoked potentials. AB - Left handers and women show less anatomical brain asymmetry, larger corpus callosum and more bilateral representation of specific functions. Sensory and cognitive components of cortical auditory evoked potentials (AEP) have been shown to be asymmetric in right handed males and to be influenced by stimulus intensity. In this study the influence of sex, handedness and stimulus intensity upon AEP components is investigated under basal conditions of passive attention. 14 right handed males, 14 right handed females, 14 left handed males, and 14 left handed females were studied while lying awake and paying passive attention to auditory stimulation (series of 100 binaural clicks, duration 1 msec, rate 1/sec, at four intensities). Cz, C3 and C4 referenced to linked mastoids and right EOG were recorded. Analysis time was 400 msec, average evoked potentials were based on 100 clicks. Stimulus intensity and gender affect early sensory components (P1N1 and N1P2) at central leads, asymmetry is influenced only by handedness, right handers showing larger P1N1 amplitudes over the right hemisphere. PMID- 1307480 TI - AIDS. A CSF laboratory experience on 470 cases in a 7 year time period. AB - In a seven year time period (July 1984 to June 1991) were studied CSF samples of 36,216 new patients, 470 of them infected by HIV. Number of AIDS patients represents 1.30% of total cases examined in the laboratory during this time period. Normal CSF was observed in only 16 cases (3.4%). Associated pathologies occurred in 66% of cases. Opportunistic infections predominated among them (227 cases). Data support indication for CSF examination in HIV infected patients. This exam must be as complete as possible. PMID- 1307479 TI - [Normal values of neural conduction velocity in a group of 101 subjects]. AB - Motor and sensory nerve conduction velocities were analysed in a group of 101 normal Brazilians. The normal values were obtained considering the group age, the distal and proximal segments of each nerve, the differences in the right and left side for each nerve. A significant decline in the conduction was found for the elderly aged group. PMID- 1307481 TI - [Peripheral facial paralysis in Petropolis]. AB - The author presents 83 cases of "a frigore" peripheral facial palsy, occurred in the mountain city of Petropolis which has characteristics such as a tropical climate without any traces of a dry season and an average temperature of 50 degrees F to 73.5 degrees F. The author relates them with virus infections which appear within a year period. Fifty six patients belong to his clinic and have a follow up, while other 25 patients proceed from another clinics and from them he only has reports on sex, age, side of palsy and the beginning of illness. He shows that the largest number of cases occurred along the months of May, August, September and October. Season distribution for southern hemisphere is analysed. He also considers etiology, incidence, prevalence, treatment and results on patients studied. PMID- 1307482 TI - [Neurologic changes in congenital heart diseases: a neuropathologic study]. AB - A neuropathologic study in 190 consecutive autopsies of patients with congenital cardiopathy was performed: 116 cases underwent a surgical procedure (S group) and the remaining 74 were non-surgical (NS group). Neuropathologic alterations were observed in 71 cases (41 in the S group and 30 in the NS group). However, most of the 129 cases with a normal examination had died in the first 72 hours either after surgery or the clinical events responsible for the death. Almost all the neuropathologic alterations were hypoxic ischemic. Infarctions, single or multiple, were found in 41 cases (23 in the S and 18 in the NS group). An embolic mechanism could be detected in 12 cases. Diffuse hypoxic changes were present in 17 cases (10 in the S and 7 in the NS group). Hemorrhages were found in 11 (6 in the S and 5 in NS group), 4 of which were related to a disseminated intravascular coagulation. In 17 cases (5 in the NS and 12 in the S group), the picture was of a periventricular leukomalacia. All these cases concerned children under 6 months of age. In 7 cases inflammatory alterations were present (diffuse micro-abscesses in 6 and a frontal lobe abscess in 1). Almost all cases in both groups presented clinical complications, isolated or associated, potentially harmful to the brain, as cardiac arrest, cardiac low output, hypoxemia, and respiratory distress. If was impossible to determine in each case the magnitude of the factor or factors responsible for the correspondent pattern of neuropathologic damage. There was no difference as to the neuropathologic pattern between congenital cardiopathies leading to increased or decreased pulmonary blood flow. PMID- 1307483 TI - [Motor neuron disease: metabolic evaluation]. AB - The authors studied serum and urinary calcium and phosphorus levels, as well as abnormalities on the spine of 30 patients with motor neuron disease. The authors believe in multifactorial aspects in the pathogenesis of motor neuron disease, calling special attention to toxic and metabolic factors. PMID- 1307484 TI - [Factors involved in the prognosis of walking in cerebral paralysis]. AB - With the objective of studying the prognosis for walking in children with cerebral palsy a retrospective survey of 100 children being treated at the Associacao de Assistencia a Crianca Defeituosa was made during the period from 1979 to 1988. The following parameters were analysed: (1) degree of motor dysfunction; (2) age of acquisition of sitting balance; (3) function of upper limbs; (4) degree of mental retardation; (5) presence of primitive reflexes. All the above parameters were analysed with respect to the capability of children acquiring or not walking. The results of our study show that the following factors are indicative of bad prognosis for walking: (1) severity of motor dysfunction; (2) acquisition of sitting posture after 3 years old; (3) precarius function of upper limbs; (4) severe mental retardation associated with severe physical deficiency. Clinical evaluation of primitive reflexes did not reveal direct relation to the walking prognosis. PMID- 1307485 TI - [Characteristics of the demand for cranial computerized tomography: reasons and costs of the exam]. AB - It was reviewed a series of 2860 cerebral computed tomography (CCT) in order to compare the main reasons at referral to investigation with the CCT results and the costs with normal and abnormal CCT. It was also studied the age and sex of the patients. Data were collected from one out of three diagnostic centers in Salvador, Brasil, for a three years period. The 2860 CCT exclude all investigation carried out for the follow-up of a previously diagnosed abnormality. CCT abnormalities were detected in 1152 (40.3%). The following reasons showed the highest proportion of abnormal CCT, for males and females respectively: demential syndrome (91.7 and 83.3%); cerebrovascular accidents (85.1 and 73.6%); infectious and parasitary diseases (76.5 and 78.6%); tumors (65.8 and 55.4%); and head injuries, 63.6% for males. In the female group, 65.0% of the CCT were normal, in a range of 65.0 to 80.0% for the age groups under 54 years old. In the male group, the highest proportion of normal CCT was found in the age groups: 25-34 (68.4%), < 15 (62.9%) and 35-44 (62.7%). The most common reasons for normal CCT for males and females were: headache (81.3 and 87.5%); dizziness/vertigo (79.3 and 78.6%); seizures (67.3 and 70.0%); psychomotor deficiency (72.0 and 67.7%) and "endocrine disorders", 75.0% for each sex. The highest proportion of normal CCT (65.3%) was requested by medical "convenios". The cost with normal CCT reached US$565,225 and with the abnormal ones, US$381,247. Costs with normal CCT were 2.2 higher for medical "convenios" as compared to those of the National Institute of Security requests and 2.8 more than those of private medicine. PMID- 1307486 TI - [Zinc in the treatment of hepatolenticular degeneration: report of 3 cases]. AB - Three patients with symptoms and signs of hepatolenticular degeneration (HLD) who developed serious renal side effects of D-penicillamine (DP) had their therapeutic schedule changed to zinc. Patient 1, a 55 year-old man had been well until 12 years old, when skeletal changes (osteomalacia) due to tubular renal disturbance began. His diagnosis of HLD had first been established at age of 32 when he presented with "wing-beat" tremor. He was then begun on DP and his neurological symptoms resolved within one year of initiating therapy but skeletal abnormalities remained unchanged as a sequel. During the next 22 years the patient was continued on DP therapy but with poor compliance. Then the reappearance of his neurological manifestations occurred several times. By the age of 53, after one year without therapy, his neurological status has worse. DP was reinstituted but some weeks later his renal laboratory parameters became severely affected. DP was discontinued and zinc sulfate (220 mg three times daily) was introduced. On this therapeutic regimen his renal laboratory parameters returned to previous level after one month. Within one year on this therapeutic regimen neurological manifestations were resolved. After 31 months on zinc treatment he remains neurologically asymptomatic and his renal function is satisfactory. Patient 2, a 41 year old woman had been her diagnosis of HLD at age of 20, when following the diagnosis of the disease in her old brother, she was found to have the laboratory features of HLD and bilateral Kayser-Fleischer rings. DP treatment was recommended at that time but she quit the follow-up. When she was 23, an esophageal variceal bleeding occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307487 TI - Evidence for a modular structure of the homologous repetitive C-terminal carbohydrate-binding sites of Clostridium difficile toxins and Streptococcus mutans glucosyltransferases. AB - The homologous C-terminal repeats of Clostridium difficile toxins (ToxA and ToxB) and streptococcal glucosyltransferases appear to mediate protein-carbohydrate interactions at cellular binding sites with sugar moieties as substrates. A consensus sequence of 134 repeating units from gram-positive bacteria indicates that these repeats have a modular design with (i) a stretch of aromatic amino acids proposed to be involved in the primary carbohydrate-protein interaction, (ii) an amplification of this interaction by repetition of the respective sequences, and (iii) a second domain, not characterized, that is responsible for carbohydrate specificity. PMID- 1307488 TI - Interleukin-11: a novel stroma-derived cytokine. AB - Interleukin-11 (IL-11) is a novel stroma-derived cytokine that acts on both hematopoietic progenitors and stromal cells. IL-11 was originally identified in a medium conditioned by the macaque bone marrow-derived stromal cell line PU-34 and cloned as a growth factor for the IL-6-dependent plasmacytoma cell line T1165. IL 11 stimulates T-cell dependent development of antibody-producing B cells and is synergistic with IL-3 to stimulate megakaryocyte colony formation. Adipogenesis inhibitory factor (AGIF) was cloned from the human bone marrow-derived stromal cell line KM-102. The AGIF cDNA sequence was revealed to be identical to that of the IL-11 cDNA. AGIF inhibits the process of adipogenesis of the bone marrow derived preadipocyte cell line H-1/A. Other biological activities such as stimulation of stem-cell proliferation, erythropoiesis, lymphohematopoiesis and hepatic acute-phase response are also summarized. The human IL-11 gene consists of five exons and four introns, and was mapped on chromosome 19 at band 19q13.3 q13.4. A single class of high-affinity IL-11 receptor (IL-11R) of 151 kDa is present on 3T3-L1 preadipocytes. A protein-tyrosine kinase pathway may be involved in the initiation of the IL-11R-mediated signal transduction. PMID- 1307489 TI - Interleukin 10: an overview. AB - Since the original description of interleukin-10, a wealth of information concerning its biological properties has been gathered. Studies in vitro have rapidly identified both immunostimulatory and immunosuppressive activities for IL 10. Based on these findings, in vivo studies were initiated in a variety of animal disease models to assess the importance of these activities. This review will summarize the pleiotropic properties of IL-10 and will survey current research regarding the potential of IL-10 to regulate acute and chronic inflammatory reactions. PMID- 1307490 TI - Clinical applications of interleukin-2. AB - Interleukin-2 (IL-2) is a cytokine with potent immunomodulating properties which has shown considerable antitumour activity in preclinical models. In clinical trials, the effects of IL-2 given by various routes and schedules have been investigated. IL-2 has been administered either as single drug or in combination with other cytokines and immunomodulating agents, chemo therapeutic agents, or reinfusions of ex vivo activated autologous cytotoxic effector cells. The results of published clinical studies with IL-2 based immunotherapy are reviewed in this paper. PMID- 1307491 TI - Evaluation of the role of cytokines in autoimmune disease: the importance of TNF alpha in rheumatoid arthritis. AB - Cytokines and growth factors are involved in all important biological processes. Hence it is anticipated that they will be of importance in autoimmune disease. The pathogenesis of autoimmune diseases involves a number of stages, initiation, perpetuation and tissue damage, each of which involves different cell and molecular interactions. In this review, we will discuss an outline of the cytokine involvement in the various stages of autoimmune development, prior to focusing on the analysis of cytokines in rheumatoid arthritis. Cytokines exert their effect via high affinity cell surface receptors. Thus an understanding of cytokines involves the analysis of receptor expression, and also of cytokine inhibitors. Currently there is only adequate knowledge of these aspects in rheumatoid arthritis (RA), and as such the emphasis of this review is on RA. One of the major reasons for being interested in the role of cytokines in autoimmunity is to define possible therapeutic targets. There is now considerable evidence that TNF alpha is such a target in RA, and the effect of anti TNF alpha monoclonal antibody therapy in RA is discussed. PMID- 1307493 TI - Bibliographic update: growth inhibitors. PMID- 1307492 TI - The molecular and cellular biology of insulin-like growth factor II. AB - Insulin-like growth factor II (IGF-II) is a 67 amino acid polypeptide that belongs to the family of insulin-like peptides. The IGF-II gene is coupled to the insulin gene and paternally imprinted. Multiple IGF-II mRNAs with identical coding regions and 3' untranslated regions (UTRs) but different 5' UTRs are generated from 3 promoters. The transcripts are translationally discriminated and inactivated by a specific endonucleolytic cleavage in their 3' UTR. These features may be important in the control of IGF-II production. IGF-II functions in an auto- and paracrine manner and binds to two types of receptors. The IGF-I receptor that is a tyrosine kinase and closely related with the insulin receptor and the IGF-II/mannose 6-phosphate (IGF-II/Man 6-P) receptor that is identical with the cation-independent mannose 6-phosphate receptor. The mitogenic and metabolic actions of IGF-II are propagated by the IGF-I receptor. In contrast, the IGF-II/Man 6-P receptor, that target lysosomal enzymes from the Golgi apparatus or the plasma membrane to the lysosomes, mediates the rapid internalization and degradation of IGF-II. IGF-II is expressed at high levels during foetal life and it is a major growth factor for the foetus in rodents. The developmental profiles and tissue distribution of the IGF-I and the maternally imprinted IGF-II/Man 6-P receptors both parallel that of IGF-II. In this scenario IGF-II promotes the growth of the embryo through the IGF-I receptor, whereas the IGF-II/Man 6-P receptor balance the activity by controlling the extracellular level of IGF-II. PMID- 1307494 TI - Volatile N-nitrosamines in salted fish samples from high- and low-risk areas for NPC in China. AB - Four carcinogenic volatile nitrosamines (N-dimethylnitrosamine, NDMA; N diethylnitrosamine, NDEA; N-nitrosopyrroline, NPYR; and N-nirosopiperilidine, NPIP) were screened in twenty specimens of salted fish collected from areas in China with different nasopharyngeal carcinoma (NPC) mortality rates. The highest NDMA, NDEA and total N-nitrosamine contents (322.92, 50.27 and 373.19 micrograms/kg, respectively) were found in the samples from Sihui, one of the areas with highest NPC mortality. The lowest contents (12.64, 7.65 and 20.29 micrograms/kg, respectively) were seen in the samples from Shanghai, the area with the lowest mortality from NPC in the study. These results confirm that there are appreciable levels of nitrosamines in the salted fishes consumed by residents in high-risk areas of NPC in China. PMID- 1307496 TI - Study of experimental hypoparathyroidism in rats. III. Fluidity changes in brain synaptolemma. AB - The changes of brain synaptolemma fluidity in experimental parathyroidectomized (PTX) rats were studied by using fluorescence polarization and differential scanning calorimetry (DSC) techniques. The results showed that microviscosity (eta) of the rat brain synaptolemma in the cerebral cortex, hippocampus, midbrain and striatum were decreased after a 2-month period of continuous hypocalcemia, and in the hippocampus and cerebral cortex it was decreased significantly as compared with control. These results suggest that the fluidity of the synaptolemma in the brains of hypocalcemic rats is increased. In addition, hypocalcemia also lowered the Tc of hippocampus synaptolemma lipid, which indicates that both fluidity and permeability had increased in these rats. PMID- 1307495 TI - Detection of point mutations of the phenylalanine hydroxylase gene and prenatal diagnosis of phenylketonuria. AB - The known mutant alleles of the human phenylalanine hydroxylase (PAN) gene were analyzed in 25 phenylketonuria (PKU) families from North China by using polymerase chain reaction and allele-specific oligonucleotide dot blot hybridization techniques. The results showed that the six mutations analyzed accounted for 62% of all PKU genes. The three most frequent mutations were R243Q, R413P and Y204C. Seven prenatal gene diagnoses were carried out in 6 PKU families and were confirmed after birth or by examination of aborted materials. PMID- 1307497 TI - An epidemiological survey of deformities and disabilities among 14257 leprosy patients in 11 counties. AB - This study was planned and conducted in 11 counties in Yangzhou Prefecture, which had formerly had a high prevalence of leprosy. Out of 14257 leprosy patients, 8122 (56.97%) with permanent deformities and disabilities were found. The disability rate was much higher among patients with multibacillary (MB) leprosy (81.15%) than among those with paucibacillary (PB) leprosy (53.04%). The statistical data involving the patients and the types of deformities and disabilities are presented in this paper, and the influences of various host factors and disease factors are discussed. PMID- 1307498 TI - The value of hysteroscopy in the diagnosis of infertility and habitual abortion. AB - Ninety cases of infertility and habitual abortion were analyzed by hysteroscopy between April 1983 and July 1990 in PUMC hospital. Abnormal changes of the uterine cavity were seen in 74.4%. The result of hysterosalpingography corresponded with that of hysteroscopy in 62.5%, and the result of B-ultrasound corresponded to that of hysteroscopy in 52.5%. The diagnosis of adhesion and polyps of the uterine cavity was made accurately by hysteroscopy, and both could be operated under hysteroscopy. After operative removal of the adhesion, an IUD should be put into the uterine cavity for 3 months. In 60 cases operations were performed during or after hysteroscopy. Of the 45 patients followed, 19 achieved pregnancy. Five patients achieved pregnancy after operative removal of the adhesion. It is concluded that hysteroscopy is more important than B-ultrasound and hysterosalpingography in the examination and treatment of infertility. PMID- 1307499 TI - Application of ABCD double feedback management in quality assurance of diagnostic radiology. AB - This method combines modern management and statistical methods with traditional film-reading systems to form a new retrospective and prospective film-reading system for quality assurance in X-ray diagnostic imaging. This method also provides feedback information with A, B, C, D and W factors which reflect the drawbacks of the radiographs. The ABCD double-feedback management system is an imaging quality evaluation system which concentrates on several important time and space periods in the radiographic engineering process. It incorporates adjustment of the X-ray apparatus and its functional capacity, selection of X-ray equipment, and application of the technician's experience and duty in the X-ray room and dark room. PMID- 1307500 TI - The effect of multi-glycosides of Tripterygium wilfordii Hook f. (GTW) on the survival time of cardiac allografts in rats. AB - Heterotopic heart transplantation was carried out in rats and the influence of multi-glycosides of Tripterygium wilfordii Hook f. (GTW) and a subtherapeutic dose of cyclosporine A (CsA) on the mean survival time (MST) of the cardiac allografts was investigated. The results showed that the MSTs of cardiac allografts in both the GTW and CsA-treated groups were significantly prolonged (P < 0.01 vs control). The rate of allograft rejection in the drug-treated groups was much lower than that in the control group. PMID- 1307501 TI - The diagnosis and steroid "pulse" therapy of systemic lupus erythematosus associated with mental disturbances in the general hospital. AB - Twenty-eight patients suffering from systemic lupus erythematosus (SLE) associated with mental disturbances were analyzed clinically (1983-1990). Although no characteristic features of the mental disturbances of SLE were found, it should be differentiated from steroid- or chronic renal failure-induced mental disorders. One gram of methylprednisolone intravenously daily for 3 days was recommended as a pulse therapy to treat the mental disturbances of SLE. In this group, the mental disturbances of SLE showed improvement or disappearance in 18 of 25 patients (72%) after pulse therapy. PMID- 1307502 TI - Advances in research on leptospira and human leptospirosis in China. AB - Leptospirosis exists in 26 of 30 provinces (exclusive of Taiwan province) in China. Up to now, a total of 18 serogroups and 70 serovars of pathogenic leptospires have been identified, including 35 serovars first found in China. A great deal of work has gone into the study of the leptospires and leptospirosis, and the present paper reviews these works, concentrating on serovar lai (the major serovar in China) and pulmonary diffuse hemorrhage (PDH), a traumatic consequence of leptospirosis. PMID- 1307503 TI - A patient with four different kinds of skin tumors on the forehead. PMID- 1307504 TI - [Diaphanization: modifications of organ weight and volume]. AB - The diaphanization of organs previously injected with coloured substances is an excellent auxiliary method of numerous morphological studies. The authors studied 52 organs, among 15 were taken from human beings and 37 from dogs, with the aim of knowing theirs weight and volume modifications after diaphanization. The organs were diaphanizated with several impregnations in 10% formaldehyde, perydrol, acetone and at least embedding in a mixture of methylsalicylate and benzyl benzoate by vacuum process. After each embedding, weight and volume of each organ were measured. The variations that the organs suffered were statistically considered, under a few aspects: 1-global organs' variations after each embedding 2-different organs' variations 3-comparison between human being and experimental animals. In all cases, the authors noticed a great decrease of weight and volume, especially after dehydration steps with acetone and clearing with the mixture of methylsalicylate and benzyl benzoate. We also didn't find any significant difference between human organs and those taken from dogs. PMID- 1307505 TI - [Vascularization of the common fibular nerve]. AB - The vascularization of the common fibular nerve (CFN) let us suppose that one have to take anatomy and physiology of vasa nervorum in consideration in the genesis of neurologic lesions. This study is based on fresh cadavers dissections, with intra arterial injection of minimum colored latex. The results emphasize the causes of the CFN susceptibility while compression and stretching injury. PMID- 1307506 TI - Histochemical localization of salivary glycoproteins in the submandibular gland of aging rats. AB - It is known that submandibular glands produce serous saliva in the serous demilune cells and mucous saliva in the mucous acinar cells which is a viscous, rich in glycoproteins substance. The aim of this study was the comparative histochemical investigation of acid and neutral salivary glycoproteins in the acinar cells of the submandibular gland in adult and aging rats. Three groups of female Wistar rats were studied: a) young adult rats, 3 months old, b) aged rats 25 months old, c) aged rats 30 months old. Each group included 5 animals. The animals were sacrificed with ether in toxic dose. The submandibular glands were dissected and placed in 10% formaldehyde solution. After fixation they were embedded in paraffin. The paraffin sections were stained with various techniques. We used the: a) Alcian-Blue PH 2,5-Neutral Red b) Periodic-acid/Schiff/Diastase c) Alcian-Blue PH2,5 and Periodic-acid/Schiff/Diastase. We observed that the acinar cells of the aged submandibular glands were filled with acid glycoproteins, while the neutral glycoproteins were localized only in the group of the adult rats. Our results confirm the theory, that lithiasis and chronic inflammations of the submandibular gland, which often happen after the 4th decade of the life, are due to alterations of the mucosubstance composition of the acinar cells. PMID- 1307507 TI - Congenital syndromes connected with tongue malformations. AB - Malformations of the tongue, are structural defects, present at birth and happening during embryogenesis. Developmental anomalies or defects may be major or minor, single or multiple, depending on their size, site and effect. The aim of this study was to present and to describe congenital syndromes which are associated with tongue malformations and to classify these malformations in groups, according to the tongue's clinical manifestations. The most common malformations of the tongue combined with syndromes associated with them, are fully discussed in this review article. Malformations of the tongue which are discussed in this review article, have been classified in the following categories: 1. Aglossia 2. Microglossia 3. Tongue hemiatrophy 4. Tongue hemihypertrophy 5. Macroglossia 6. Long tongue 7. Ankyloglossia 8. Cleft or bifid tongue 9. Syndromes that affect tongue and cannot be classified in a special condition Each category is discussed separately in this article. PMID- 1307508 TI - [Drainage of the erectile organs in the rat]. AB - The retro-pubic veinous circle of the male rat was investigated on the both sides: anatomic and functional aspect. The dorsal vein of penis in the male rat run into a retro-pubic veinous circle. This circle receive the anterior vesical veins too. The internal pudendal vein and the anastomotic vein begin in this circle, and go together to the iliac vein. From the retro-pubic veinous circle, there is a triangular circulation between the internal pudendal vein, the anastomotic vein and the iliac vein. Angiographies performed on rats in vivo, indicates that the anastomotic vein is effical for the drainage of the retro pubic circle only if the flow of the penis dorsal vein is sufficient. These conclusions are proved by experimentation on dead rats. PMID- 1307509 TI - [Investigation of interleukin 2 receptor and T cell subsets in the patients with tuberculous meningitis]. AB - Interleukin 2 receptor (IL-2R) on lymphocyte and T cell subsets of peripheral blood(PB), defined by monoclonal antibodies, were studied in 25 patients with tuberculous meningitis. 25 staff members served as PB control. Dynamic changes of IL-2R positive cells and T cell subsets were observed in 10 of 25 patients at sixth week after chemotherapy. IL-2R positive cells showed higher percentages in the patients than in healthy controls. Percentages of CD5and CD4cells were lower than those of healthy control. With chemotherapy, the percentages of CD4cells raised. The results indicated that M. tuberculosis might stimulate T cell to express IL-2R. A lower cell mediated immunity function in the patients with tuberculous meningitis was characterized by CD4 lymphopenia. PMID- 1307510 TI - [Clinical analysis of 41 cases of pulmonary atypical mycobacteriosis]. AB - This paper reported forty-one patients with pulmonary atypical mycobacteriae infection from Jan. 1988 to Oct. 1990 in our hospital. 25 male and 16 female. The age ranged from 27 to 70 years, average 50.9 years. According to Runyon classification of mycobacterium diseases, there are 4 cases with Mycobacterisos kansasii, 2 with M. scrofulaceum, 14 with M. intracellulare or M. avium, 9 with M. chelonae and 12 with M. fortuitum, respectively. Characteristics of this disease were long history, mild symptom and unsatisfactory therapeutic effect by anti-tuberculosis drugs. PMID- 1307511 TI - [Determination of interleukin 2 activity in patients with pulmonary tuberculosis]. AB - The activity of Interleukin-2 (IL-2) in 34 patients with pulmonary TB and 25 normal adults were determined by means of the bioassay. The results showed that the activity of IL-2 determined by immediate stimulating method (Ohs IL-2) and delayed stimulating method (24hs IL-2) are markedly increased in the mild cases than that of controls; In the advanced cases and the controls, no significant difference was found between the activities of ohs IL-2, but the activity of 24hs IL-2 is markedly reduced in the former group. All these showed that the activity of IL-2 is depended on the serious degree of illness and the clinical type, it can also reflect the condition of immune function in the patients with pulmonary TB. PMID- 1307512 TI - [Experimental studies of lung lesions in rabbits caused by Streptomyces thermohygroscopicus]. AB - Imitating the natural way of infection of Farmer's lung disease, we succeeded in inducing acute lesions of Farmer's lung disease in rabbits by the dry powder of thermohygroscopicus. Histopathological examination revealed typical interstitial pneumonitis, alveolitis and bronchiolitis. One week after the inhalation of the dry powder of thermohygroscopicus, the precipitins could be detected in the rabbits' serum by immunoblotting. Depending on the lung lesions of rabbits, we discussed the pathogenetic mechanisms of Farmer's Lung. PMID- 1307513 TI - [Pulmonary clearance of 99mTC-DTPA aerosol in patients with silicosis]. AB - 99mTc-DTPA clearance was studied in 11 healthy nonsmokers, 20 patients with simple or complicated silicosis (5 of simple, 15 of complicated). The results indicated that both the patients with simple silicosis (T1/2 32.8 +/- 14.4min) and complicated silicosis (T1/2 26.6 +/- 8.5min) showed faster clearance of inhaled 99mTc-DTPA than observed in healthy nonsmokers (77.9 +/- 11.7min, p < 0.01). Regional clearance apico-basal difference was found in patients with silicosis. This study presents evidence of increased pulmonary epithelial permeability and regional distribution of pulmonary epithelial permeability in silicosis. PMID- 1307514 TI - [A quantitative analysis of pulmonary arterioles in 402 cases of cor pulmonale]. AB - A quantitative analysis of pulmonary arterioles were made in 402 cases of cor pulmonale. The results showed that arteriole muscularization and medial hypertrophy, intimal fibrosis of pulmonary small arteries were important lesions. The authors found that right ventricular hypertrophy was bound to follow intimal fibrosis of pulmonary small arteries but was not along with medial hypertrophy and arteriole muscularization, and that the lesion of pulmonary arteries was not balanced with the course of disease. The authors considered that these results were related to vessel dilatation and medial atrophy because of intimal pressure in late stage of the disease. PMID- 1307516 TI - [A comparative study of the effects of control ventilation and synchronized intermittent mandatory ventilation on hemodynamic and blood gases in patients with chronic obstructive pulmonary disease]. AB - Effects of control ventilation (CV) and synchronized intermittent mandatory ventilation (SIMV) were comparatively studied in 9 patients with chronic obstructive pulmonary disease. Cardiac index (from 2.99 +/- 0.65 to 3.60 +/- 0.651.min-1.m-2, P < 0.05) and oxygen delivery index (from 537 +/- 89 to 645 +/- 101 ml.min-1.m-2, P < 0.05) were significantly increased during SIMV comparing with CV. Mixed venous oxygen tension (from 5.63 +/- 0.66 to 6.06 +/- 0.59 kPa, P < 0.01) was improved by SIMV. The results showed that SIMV could improve cardiac output, oxygen delivery and oxygen supply of tissue. PMID- 1307515 TI - [Effect of ligustrazine controlled release capsule on pulmonary hemodynamic and right ventricular systolic time intervals in patients with cor pulmonale]. AB - Before and after oral administration of Ligustrazine controlled release capsule, pulmonary hemodynamic and right ventricular systolic time intervals, arterial blood gas and TXA2/PGI2 were studied. It was shown that decreasing of pulmonary arterial pressure and pulmonary vessel resistance, and heart rate, increasing of cardiac output, right ventricular systolic time intervals and arterial blood gas improving after one course of treatment with Ligustrazine controlled release capsule. It suggested that vasodilation caused by Ligustrazine is probably related to its vasodilating pulmonary vessela and improving imbalance between TXA2/PGI2 in patients with Cor Pulmonale. PMID- 1307517 TI - [Effects of inhaled aerosol of platelet activating factor on pulmonary function and airway responsiveness in normal subjects]. AB - Platelet activating factor (PAF), which was given as an aerosol to normal subjects, caused immediate bronchoconstriction. After the first inhalation of PAF, percentage fall of VP30 was 43.2% +/- 7.1% at five minute. Subsequent inhalations of PAF, bronchoconstriction effect of PAF gradually attenuated. There was an increase in the airway responsiveness to methacholine following inhalation of PAF. The mean PC40 fell from 18.57 +/- 1.69 g.L-1 to 7.01 +/- 2.24g.L-1 (P < 0.01) on day three and returned to baseline in 1 to 2 weeks. DLCO decreased from 3.3 +/- 0.7ml.kPa-1/s to 2.9 +/- 0.4ml.kPa-1/s (P < 0.01) on day three. Chlorpheniramine partially inhibited the bronchoconstriction effect of PAF in a double blind, crossover study. These data suggest that PSF may contribute to the pathogenesis of airway hyperresponsiveness in asthma and the bronchoconstriction induced by inhaled PAF is mediated in part by histamine release. PMID- 1307518 TI - [The effect of dilution and heparin on the blood gas analysis]. AB - The effect of heparin on the measurement of blood gases is mainly caused by dilution, which substantially reduces the PCO2 and HCO3- values. Excess heparin will change the pH, PCO2 and 3- as a consequence of an alternation in H+ ionconcentration. The effect of dilution on electrolytes depends on the respective electrolyte concentration in diluent. Dilution reduces the glucose value, but to a higher degree as could be expected from a dilution effect. Heparin binds electrolytes and influences the results, especially the calcium ion. As a result of this investigation we recommend the 20IU or less heparin be used for multi-electrolyte determination with or without blood gas analysis, and that the dilution of sample be maintained at less than 5%. In other words, at least a 3ml or 2ml blood sample should be collected in a 5ml or 2ml glass syringe, the corresponding heparin concentration is 400kU/L or less. PMID- 1307519 TI - [Clinical and radiological studies on 15 cases of acute phosgene poisoning]. AB - A clinical and radiological observation on 15 cases of acute phosgene poisoning were reported. The pulmonary edema after acute phosgene poisoning can be classified into two types: interstitial and alveolar. The X-ray findings were described in detail in correlation with the clinical symptoms. Taking X-ray early can benefit on preventing and treating acute pulmonary edema. Meanwhile, the patients with chronic respiratory or digestive diseases can develop pulmonary encephalopathy or upper gastrointestinal bleeding after acute phosgene poisoning. PMID- 1307520 TI - [Disseminated Mycobacterium avium complex infection]. PMID- 1307521 TI - [Cryotherapy in pulmonology]. PMID- 1307522 TI - Genetic and environmental determinants of non-insulin-dependent diabetes mellitus (NIDDM). PMID- 1307523 TI - Primary prevention of non-insulin-dependent diabetes mellitus. PMID- 1307524 TI - An epidemiological perspective of the relationship between physical activity and NIDDM: from activity assessment to intervention. PMID- 1307525 TI - Obesity and diabetes in "the land of milk and honey". PMID- 1307526 TI - The economic costs of NIDDM. PMID- 1307527 TI - The changing faces of salmonellosis. PMID- 1307528 TI - Infective endocarditis--pitfalls in diagnosis and therapy. PMID- 1307529 TI - Early pre-diabetic hormonal changes in diabetes mellitus--their significance. PMID- 1307530 TI - Changing spectrum of clinical and laboratory profile of infective endocarditis. AB - The clinical profile of 28 consecutive patients admitted with infective endocarditis (IE) between 1987 and 1988 was studied. There were 21 males and seven females with a mean age of 24 +/- 11 years. Rheumatic heart disease (RHD) was the commonest underlying disease (68%) followed by congenital heart disease (CHD). Mitral regurgitation with aortic regurgitation were the commonest valvular lesions (47%) in those with RHD while ventricular septal defect was the commonest (43%) in those with CHD. A younger age of onset, complicated course and high mortality were seen in these six patients with acute IE. Persistently positive blood cultures during life or at autopsy were obtained in 21%. Strep viridans was the commonest isolate and was often resistant to streptomycin. 2D echocardicgram revealed vegetations in 96% of patients, the aortic valve (39%) being more commonly affected than the mitral valve (11%). ESR of more than 20 mm drop 1st hour (Wintrobe) was seen in 96%. Thrombophlebitis was a common complication of therapy and cloxacillin the commonest drug implicated. A mortality of 21% as a result of refractory congestive heart failure (CHF) (50%), uncontrolled sepsis (33%) and embolic events (17%) was seen. A rising incidence of culture negative IE, combined aortic and mitral valve disease and CHF is noted. PMID- 1307531 TI - Glucagon response to glucose load in offspring of conjugal type 2 diabetic parents in south India. AB - Immunoreactive glucagon responses were measured in 21 normoglycaemic adult offspring of non-insulin dependent (Type 2) diabetic parents, in the fasting state and during an oral glucose tolerance test. In 7 of the 21 offspring, the mean fasting immunoreactive glucagon value was significantly lower than the control value (p < 0.001). In this group, glucose stimulation did not produce inhibition of immunoreactive glucagon secretion. The insulin response in this group was not significantly different from the values in the other study groups. In the other 14 offspring, the pattern of glucagon response to glucose stimulation was similar to controls. It is likely that this non-suppressive effect of glucose on immunoreactive glucagon in some of the "prediabetic" individuals is an early change in the alpha cell function during the natural history of non-insulin dependent diabetes in Asian Indian subjects. PMID- 1307532 TI - Changing profile of enteric fever--in summer-91. AB - The clinical presentation, complications and sensitivity pattern was studied in 30 cases of enteric fever. Fever was the main presenting feature in all. Other associated predominant presenting feature were vomiting in 15 (50%), Loose motion 9 (30%), Cough 6 (20%), headache 4 (13.33%) and altered sensorium in 2 (6.66%). The various complications observed during hospital stay were myocarditis 5 (6.16%), Paralytic ileus 2 (6.66%), Pneumonia 1 (3.33%) and Joint effusion in 2 (6.66%) cases respectively. In laboratory parameters-mild elevation of blood urea and SGOT/SGPT were detected in 1st week, which returned to normal in 2-3 weeks time. In vitro sensitivity of organism isolated (24 cases) were as follow- Chloramphenicol 7 (29.16%), Ampicillin 8 (33.33%), Gentamicin 22 (91.66%), Amikacin 24 (100%), Cefotaxime 22 (91.66%), Ciprofloxacin 24 (100%), and Ofloxacin 24 (100%). Clinical response to Ofloxacin and Ciprofloxacin was 100%, and fever subsided in 3-5 days. PMID- 1307533 TI - Chloramphenicol resistance in Salmonella typhi. Report from Bombay. AB - Chloramphenicol resistance to Salmonella typhi in 1989 was 16% in Hinduja Hospital. From Jan to June 1990, this resistance has increased to 81%. 74 strains of blood culture isolated of S typhi obtained from Jan to June were subjected to antibiotic sensitivity testing by disc diffusion technique of Kirby and Bauer 60 strains were found to show a block resistance tochloramphenicol, Ampicillin, Co trimoxazole, Streptomycin, Tetracycline and Carbenicillin. All strains were sensitive to quinolones. Resistance was record and MIC done in 50 resistant strains by modified National Committee for Clinical Laboratory Standards [NCCLS] according to recommended break points and resistance to Chloramphenicol was confirmed. Of the 47 strains isolated, 34 had received treatment with either chlorampheniicol, Ampicillin or Cotrimoxazole in adequate dosages. In 39 of these 47 patients, Salmonella typhi was isolated after 14 days duration of fever. Plasmid analysis revealed presence of 100 megadalton plasmid in majority of cases. Most patients responded to fluoroquinolones but amongst the admitted patients complications such as Myoglobinuria in 2 cases, perforation in 4 cases, acute Renal failure in 2 cases and typhoid spine in 1 case were seen. Phage typing results of 19 strains were E-8, 0-6. PMID- 1307534 TI - Retrospective treatment analysis of Salmonella infections. AB - Twenty four culture proved and nine postmortem histopathology proved cases of enteric fever were analysed retrospectively with special interest in use of various antisalmonella agents. Chloramphenicol resistance was noted in 91.7% and yet 70% of all patients received chloramphenicol alone or in combination with another antisalmonella agent. Time required for remission of fever with chloramphenical, cotrimoxazole and ciprofloxacin was 4.5, 4.1 and 6.9 days respectively. An interesting feature noted in post-mortem histopathology proved cases was enteric carditis which was documented on postmortem examination of the heart in three out of four patients who died of peripheral circulatory failure. PMID- 1307535 TI - Dapsone in cutaneous lesions of SLE: an open study. AB - This short report describes a possible beneficial effect of dapsone in the treatment of chronic unresponsive muco-cutaneous lesions of systemic lupus erythematosus (SLE) without any serious side effects. PMID- 1307536 TI - Diltiazem as adjunctive oral therapy in patients with chronic atrial fibrillation. AB - Digoxin frequently fails to control the heart rate in patients of chronic atrial fibrillation particularly during exertion. We have studied in 20 such patients the effect of adding diltiazem (180 mg/day) on resting and peak exercise heart rates. An attempt was also made to determine its effects on exercise tolerance by using treadmill and 6 minute walk test. Addition of diltiazem resulted in significant attenuation of heart rate both at rest and at peak exercise. The resting and exercise mean heart rates on digoxin alone were 98.9 +/- 21.5 b.p.m. and 160.2 +/- 35.68 b.p.m. respectively. After diltiazem this reduced to 78.7 +/- 12.30 b.p.m. at rest and 132.4 +/- 40.4 b.p.m. at peak exercise (p < 0.01). There was no significant effect on exercise tolerance. In conclusion, the addition of diltiazem substantially reduced the excessive heart rate response to exercise in digitalised patients of chronic atrial fibrillation. PMID- 1307537 TI - Neurological manifestations of leukemia--clinical and pathological findings. AB - Out of 70 cases of leukemia studied, 19 had neurological manifestations. All cases were autopsied. Leukemic infiltrates and intracranial hemorrhages produced various neurological manifestations. In autopsied cases 37.2% showed infiltrative changes. Intracranial hemorrhages contributed to 20%, the cause of which were due to thrombocytopenia and leukostasis. Leukemic nodules, demyelination and astrocytosis, gliosis were also seen on histopathology. PMID- 1307538 TI - Therapeutic drug monitoring (TDM). PMID- 1307539 TI - The lungs in heatstroke. PMID- 1307540 TI - Pregnancy and diabetes--review. PMID- 1307541 TI - Paraganglioma of the cauda equina. AB - A case of paraganglioma of the cauda equina is presented. Usually reported to be benign with good prognosis, the present patient had a somewhat different course. The behaviour of the tumour was unusual, with rapid recurrence seen within first month of surgery. The need for total surgical excision and role of adjuvant radiotherapy is highlighted. PMID- 1307542 TI - Pituitary and testicular involvement in primary haemochromatosis. A case report. AB - A case of primary hemochromatosis with hypogonadotropic hypogonadism and decreased Leydig cell reserve is reported. PMID- 1307543 TI - Rhythmic palatal myoclonus. AB - We report two cases of rhythmic palatal myoclonus (RPM) first presenting with symptoms unrelated to myoclonus and a possible etiology of encephalitis and the second presenting with ear click and palatal myoclonus. The response to treatment was unsatisfactory in both. PMID- 1307544 TI - Silicotic alveolar proteinosis with bilateral spontaneous pneumothorax. AB - Bilateral spontaneous pneumothorax due to silicotic alveolar proteinosis is reported because of its rarity. PMID- 1307545 TI - Malignant mesothelioma of peritoneum. A case report. PMID- 1307546 TI - Non-Hodgkins lymphoma presenting as pure red cell aplasia. AB - An interesting case of Non-Hodgkins lymphoma presenting as pure red cell aplasia is being reported. Even though acquired pure red cell aplasia is not uncommon, lymphoma presenting as pure red cell aplasia is very rare. The patient responded to COP treatment and red cell transfusion and is on regular follow up. This appears to be the first report of such an association in Indian literature. PMID- 1307547 TI - Thyrotoxic periodic paralysis. PMID- 1307548 TI - Klebsiella pneumonia with lung abscess in a male child. AB - An unusual presentation of Klebsiella pneumonia with lung abscess in a male child with no apparent predisposing factor is described. PMID- 1307549 TI - Platelet aggregation in migraine. PMID- 1307550 TI - Priapism in malaria. PMID- 1307551 TI - Calcium imbalance in hypoparathyroidism. PMID- 1307552 TI - Incubation period of rabies: how long could it be? PMID- 1307553 TI - Adenosine deaminase in the diagnosis of tubercular pleural effusion--how far it is helpful. PMID- 1307554 TI - [A clinicopathologic study of atrial infarction complicating left ventricular posterior myocardial infarction]. AB - Among a series of 400 consecutive autopsy cases we performed a clinicopathologic study of atrial infarction in 46 autopsy-proven cases, which had acute or old left ventricular (LV) myocardial infarction. We used blocks taken from both atrial appendages, the region of the sinus-node, the lateral wall of the right atrium, the posterior wall of the right atrium, and the posterolateral wall of the left atrium. Atrial infarction was identified in 13 (28%) of 46 cases with LV posterior infarction which was caused by lesions of the right coronary artery; 10 cases were right atrial infarction and 3 were both right and left atrial infarction. Among 13 cases in which the acute phase of ventricular infarction could be followed, 3 cases exhibited transient atrial fibrillation. Of these 3 cases, 2 had atrial infarction. The mean stenotic index of the proximal right coronary artery was 4.3/5 in the 13 cases of atrial infarction, 3.2/5 in 17 cases of acute necrosis or scar and 3.1/5 in 16 cases without ischemic atrial lesions. Most of the atrial infarction was found in the right atrium; 10 in the right atrial appendage, 8 in the right atrial lateral wall, 3 in the region of the sinus node and the left atrial posterolateral wall, 2 in the right atrial posterior wall, and one in the left atrial appendage. In conclusion, the incidence of atrial infarction was unexpectedly high (28%) in LV posterior infarction caused by lesions of the proximal right coronary artery, particularly in severe stenosis or obstruction. PMID- 1307555 TI - [Left ventricular diastolic function in apical hypertrophic cardiomyopathy]. AB - To investigate left ventricular (LV) diastolic function in patients with apical hypertrophic cardiomyopathy (AHCM), we analyzed the LV cineangiograms (RAO 30 degrees) and pressures (tip manometer) in 11 patients with AHCM who had giant negative T waves on their electrocardiograms and "ace of spades" configurations on the LV angiograms. Ten patients with non-obstructive HCM (HNCM) and 10 normal subjects served as controls. LV volumes and instantaneous rates of LV volume changes were derived from frame-by-frame analyses of their LV angiograms. LV isovolumic relaxation was assessed according to the time constant (T) of LV pressure decay. LV diastolic distensibility was evaluated by plotting diastolic pressure-volume curves. There was no significant change in the LV systolic functions among these 3 groups. Compared with normals, LV end-diastolic pressure was equally elevated in AHCM and HNCM. The T of isovolumic pressure decay was significantly prolonged in AHCM and HNCM. LV early diastolic filling was maintained at the normal level in AHCM as assessed by the peak filling rate (PFR) during the rapid filling period and the time from end-systole to PFR. The LV diastolic pressure-volume relation shifted upwards in both AHCM and HNCM. In conclusion, impaired LV isovolumic relaxation and decreased diastolic distensibility, which are associated with HNCM, may also be present in AHCM. PMID- 1307556 TI - [Characteristics of acute myocardial infarction, preinfarct angina and postinfarct angina in patients with diabetes mellitus]. AB - To elucidate the characteristics of acute myocardial infarction, preinfarct angina and postinfarct angina in diabetic patients, we compared 51 diabetics and 73 non-diabetics who had myocardial infarction and angiographically-proven coronary artery stenosis. There was no statistical difference between these 2 groups with respect to age, sex, histories of smoking, hypertension and hypercholesterolemia, and hemodynamic parameters. Mean of the number of diseased vessels and of the jeopardy scores were higher in diabetics than in non-diabetics (2.4 vs. 1.9, p < 0.01; 7.2 vs. 5.7, p < 0.02, respectively). The absence of preinfarct angina (59 vs 32%, p < 0.01) and typical chest pain of myocardial infarction was more frequent in the diabetic group than in the non-diabetic group (43 vs 15%, p < 0.005). Congestive heart failure was more common in diabetics than in non-diabetics (45 vs 14%, p < 0.005). Though there was no difference in the frequency of postinfarct angina between the 2 groups (54 vs 52%), painless myocardial ischemia during treadmill exercise tests was more frequent in diabetics than in non-diabetics (75 vs 30%, p < 0.025). Compared to diabetic patients with typical chest pain of myocardial infarction, diabetics without typical chest pain had preinfarct angina less frequently (82 vs 41%, p < 0.01), but had diabetic neuropathy (71 vs 43%, p < 0.05) and retinopathy (67 vs 32%, p < 0.025) more frequently. We concluded that diabetic patients with myocardial infarction frequently lack 1) preinfarct angina, and 2) typical chest pain of myocardial infarction. 3) They often suffer from congestive heart failure, 4) frequently accompanied by painless myocardial ischemia during exercise stress tests. Therefore, special attention should be paid for the management of diabetic patients with specific neuropathy and retinopathy. PMID- 1307557 TI - [Regional myocardial coronary blood flow reserve in hypertrophic cardiomyopathy assessed by digital subtraction coronary angiography]. AB - Using digital subtraction coronary angiography (DSA), we evaluated the regional myocardial coronary blood flow reserve (rMFR) in 18 patients with hypertrophic cardiomyopathy (HCM). There were 13 patients with asymmetrical septal hypertrophy (ASH), and 5 with asymmetrical apical hypertrophy (AAH). Eight subjects without apparent cardiac abnormality served as controls. Relations between the rMFR and regional wall thickness as determined by echocardiography were also investigated. Peak contrast density (Cm) and time to Cm (Tm) were measured from digital angiograms at the middle and distal ventricular septum (VS) and at the apical and left ventricular posterior wall (PW). The rMFR of each region of interest was expressed as the ratio of Cm/Tm at the baseline and at peak hyperemic response induced by intracoronary administration of papaverine. The rMFR was significantly lower at the VS and apex in HCM than in controls: middle VS, 1.9 +/- 0.5 vs 3.9 +/- 0.5, p < 0.001; distal VS, 2.0 +/- 0.5 vs 4.4 +/- 0.9, p < 0.001; and the apex, 2.0 +/- 0.7 vs 4.5 +/- 1.6, p < 0.01. However, it did not differ at the PW; 2.6 +/- 0.9 vs 3.0 +/- 0.9 between the 3 groups. The middle VS and apex, where the wall was the thickest, had the lowest rMFR in ASH and AAH. Furthermore, at the VS and apex, a curvilinear relationship was observed between the rMFR and wall thickness (rMFR = -0.88 in WT + 2.39, r = -0.57, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307558 TI - [Extent and degree of coronary flow reserve in hypertrophic cardiomyopathy assessed by delta Fract map unfolding coronary flow reserve index]. AB - Patients with hypertrophic cardiomyopathy (HCM) are known to have ischemic events and decreased coronary flow reserve, but the variabilities in the site and degree of fall between patients with this disease have not been clarified. To elucidate these variabilities, we performed exercise myocardial single photon emission computed tomography (SPECT) using double dose method in 30 patients with HCM (6 with obstruction, 17 with non-obstruction, 7 with apical hypertrophy) and 10 normals. Then, the delta Fract (coronary flow reserve index) map was obtained for each subject. Exercise and then rest Tl-201 myocardial scintigraphy were performed after administration of Tl-201. The data were reconstructed, making the circumferential curves from the same level of short-axis imaging during exercise and at rest. By subtracting the values at rest from the values during exercise, which were divided by the values at rest, delta Fract in each frame was obtained, and described on the unfolded map. The extent and degree of coronary flow reserve were visually estimated by this delta Fract map. Patients were categorized into 5 groups: diffuse fall of coronary flow reserve (D-type), 6 cases; localized fall of the septum or lateral wall (L-type), 5 cases; fall of apical region (A-type), 5 cases; mild fall (M-type), 6 cases; and normal pattern (N-type), 8 cases. We concluded that delta Fract map is useful for evaluating the extent and degree of coronary flow reserve in HCM. PMID- 1307559 TI - [Impaired cardiopulmonary baroreflex control of forearm vascular resistance in hypertrophic cardiomyopathy]. AB - We tested the hypothesis that the cardiopulmonary baroreflex control of forearm vascular resistance is impaired in patients with hypertrophic nonobstructive cardiomyopathy (HNCM). Forearm vascular responses to lower body negative pressures (LBNP) at -20 mmHg and -40 mmHg and to lower body positive pressure (LBPP) at +20 mmHg and +40 mmHg were compared between 11 patients with HNCM and 6 normal subjects. Forearm blood flow was measured with a strain gauge plethysmograph and forearm vascular resistance was calculated by dividing mean blood pressure by forearm blood flow. The left ventricular end-diastolic dimension and the left atrial dimension changed with the increases in LBNP and LBPP in patients with HNCM and in normal subjects. The ranges of these changes were similar in the 2 groups. Mean blood pressure and heart rate did not change during LBNP and LBPP. LBNP increased but LBPP decreased forearm vascular resistance in normal subjects, but neither LBNP nor LBPP changed the resistance in patients with HNCM. Increases in the resistance to cold pressor tests did not differ between the 2 groups. In patients with HNCM, there was a negative correlation between forearm vascular resistance at LBNP -20 mmHg and the left ventricular wall thickness (r = -0.81, p < 0.01). These results suggest that the cardiopulmonary baroreflex control of forearm vascular resistance is impaired in hypertrophic cardiomyopathy and that this impairment may be associated with left ventricular wall thickness. PMID- 1307560 TI - [Left ventricular filling disturbances in cardiac amyloidosis: a study of atrial sound and diastolic inflow velocities]. AB - Cardiac amyloidosis is characterized by left ventricular filling disturbances in a relatively early stage. To investigate such disturbances more precisely, we studied atrial sound and left ventricular inflow velocity patterns. Twelve cases diagnosed as cardiac amyloidosis according to the clinical criteria including rectal biopsies and serum amyloid proteins or at autopsy were reviewed and analyzed. Their mean age was 60.9 +/- 12.5 years. Twelve age-matched cases with hypertrophic cardiomyopathy (HCM) served as the controls. We measured the amplitude of atrial sound by low-frequency phonocardiograms and the ratio of the heights of the A wave of apexcardiograms (ACG) to the total amplitude of the ACG. The mitral inflow velocity patterns were recorded using pulsed Doppler echocardiography. The rapid filling wave (R), atrial filling wave (A) and the ratio of A to R (A/R) were measured. In the amyloidosis group, atrial sound moderately increased in 2 cases, it was faint in 9 and not manifest in the remaining one. The A wave in the amyloidosis group was significantly smaller than that in the HCM group (p < 0.001) (12.4 +/- 3.9 vs 22.4 +/- 5.6%). In the left ventricular inflow velocity patterns, the R in amyloidosis was smaller than that in HCM (41.7 +/- 16.0 vs 56.4 +/- 12.1 cm/sec) (p < 0.02). The A in amyloidosis was also smaller than that in HCM (40.5 +/- 13.4 vs 58.1 +/- 13.0 cm/sec) (p < 0.006). The A/R was 1.0 +/- 0.34 in amyloidosis and 1.1 +/- 0.32 in HCM (N.S.). Both A and R were significantly less in amyloidosis than those in HCM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307561 TI - [Hemodynamic difference accounted for the orientation of a Bjork-Shiley mitral prosthesis: a color Doppler echocardiographic study]. AB - To determine whether the orientation of the major orifice of a mitral tilting disc prosthesis affects hemodynamics, intracavitary blood flow patterns were studied in 45 patients with well-functioning Bjork-Shiley mitral prosthesis using color Doppler flow imaging. The major orifice was oriented towards the septum in 23 patients (12 men, 11 women, age 58 +/- 11 years; group S), and towards the posterior wall in 22 patients (8 men, 14 women, age 55 +/- 9 years; group P). 1) The left ventricular end-diastolic dimensions (S: 4.8 +/- 0.9 cm, P: 5.2 +/- 1.0 cm), end-systolic dimensions (S: 3.6 +/- 0.9 cm, P: 3.8 +/- 1.2 cm), and left atrial dimensions (S: 5.0 +/- 1.0 cm, P: 4.7 +/- 0.9 cm) did not differ significantly between the 2 groups. 2) The peak mitral flow velocities (S: 1.43 +/- 0.38 m/sec, P: 1.43 +/- 0.27 m/sec), pressure gradients (S: 8.5 +/- 4.0 mmHg, P: 8.4 +/- 3.1 mmHg), and pressure half-times (S: 94.0 +/- 19.0 msec, P: 86.5 +/- 21.7 msec) did not differ significantly between the 2 groups. 3) Although mitral regurgitation was detected in 8 patients (35%) in the S group and in 2 patients (9%) in the P group, hemodynamically significant regurgitation was detected in only 4 patients in the S group (3 mild, one moderate). 4) The patients in the S group had reversed intracavitary blood flow; mitral flow was first directed towards the left ventricular outflow tract during diastole, while the outflow pattern was displaced into the left ventricular inflow tract.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307562 TI - A simple noninvasive measurement of stenotic mitral valve area: an alternative approach using M-mode and Doppler echocardiography. AB - Doppler echocardiography is a widely used noninvasive technique to examine the mitral valve area (MVA) by obtaining mitral pressure half-time (PHT) and to assess the severity of the stenosis. However, several hemodynamic factors influence the PHT and may render the PHT data inaccurate in any measurement of MVA under certain conditions. Using a simple echo-Doppler (E-D) method, we assessed the MVA in a physiological equation. The mitral flow volume (MFV) is represented by MVA x transmitral mean flow velocity (mV) x diastolic filling time (DFT). Thus, the formula can be restated as MVA (cm2) = MFV (cm3)/mV (cm/sec) x DFT (sec). We measured MFV by M-mode, and mV and DFT by continuous wave Doppler echocardiography. This formula was tested in 43 patients with isolated mitral stenosis. MVA was obtained by the PHT and E-D methods, and the data obtained were validated against the results of cardiac catheterization. The results obtained using the E-D method showed much better correlation (r = 0.82) with those of catheterization than those with the PHT method (r = 0.52). The inter- and intraobserver variabilities were checked. The results obtained with the E-D method were found to be reproducible. To further validate the accuracy of the E-D method, MVA was measured by both methods at different R-R intervals after exercise and the results were compared. The MVA obtained by the PHT method showed marked variations; whereas, that obtained by the E-D method remained nearly constant. Similarly, in a patient with atrial fibrillation, the MVA assessed by the PHT method varied from beat to beat; whereas, the fluctuations in MVA were minimal using the E-D method. We concluded that the E-D method can be reliable and clinically easily applicable for the accurate assessment of MVA. PMID- 1307563 TI - [Blood flow dynamics and dimensions of the descending thoracic aorta in patients with intra-aortic swirling echoes: assessment by biplane transesophageal echocardiography]. AB - To examine the blood flow dynamics in the descending thoracic aorta (DAo) where intra-aortic swirling echo contrast was observed, we analyzed the flow velocity patterns (FVP) in DAo and the DAo dimensions by biplane transesophageal echocardiography (TEE) in 9 patients with intraortic swirling echo contrast and in 25 control subjects (N). We recorded sampling volumes with pulsed Doppler echocardiograms at 3 sites: median, central, and lateral sites on longitudinal scan images and on the DAo at the level of the mitral valve. We measured systolic peak flow velocity (Vp), time from the onset of the systolic flow to Vp (acceleration time: AT), deceleration time (DT) of the systolic flow, and AT/(AT + DT) for each sampling volume in the DAo. From the M-mode echogram of DAo, we measured the maximum dimension of the aorta, which usually coincided with the mid to late systolic phase. In the normal controls, the systolic forward flow was followed by a small reversal flow in early diastole and then by a small forward flow during holodiastole. Vp was highest at the center (64 +/- 10 cm/sec), then at the median (60 +/- 11 cm/sec) and lowest in the lateral (56 +/- 9 cm/sec; p < 0.01 vs center) sites in the DAo. AT was 70 +/- 13 msec and DT 215 +/- 26 msec. This flow velocity profile in the DAo was observed in both the control and patient groups. In patients with intra-aortic swirling echoes, Vp was markedly low (33 +/- 7 cm/sec; p < 0.001 vs N) and dimension of the DAo (13 +/- 2 mm/m2 in N) was significantly enlarged (21 +/- 7 mm/m2; p < 0.001 vs N), which might be related to swirling echoes and mural thrombi at the lateral portion in the DAo. Thus, we concluded that intra-aortic swirling echoes closely related to the production of mural thrombi observed mainly at the lateral site of the significantly dilated DAo. PMID- 1307564 TI - [Three-dimensional radiologic device as a new diagnostic aid in angiocardiography]. AB - Angiography with 180 degrees arc was performed using a rapidly rotating stereoradiographic device and a single injection of contrast medium. Duration of rotation of the X-ray tube through 180 degrees was 2.25 sec. The angiograms displayed in a rotating manner were three-dimensional with depth information. Every adjacent angiograms were obtained by the rapidly rotating X-ray tube at slightly different angles and positions, resulting in paired stereo images. The angiograms can be displayed on side-by-side monitors and viewed stereoscopically with a stereoviewer. Rotating images were displayed at 30 frames/sec (60 fields/sec) and were viewed in a fluorographic manner. To apply the data to angiocardiography the following procedures were required: 1) the start of rotation of the X-ray tube was synchronized with the R wave of the EKG, 2) suspension of respiration, and 3) the subject's upper extremities were immobilized at his head. To obtain left atrial angiograms the following steps were taken: 1) the circulation time from the pulmonary artery to the left atrium was estimated by injecting 15 ml contrast medium into the pulmonary artery under the fixed X-ray tube, then, 2) X-ray exposures of 20 fields/sec were obtained during 15 sec, and 3) left atrial arteriograms were taken by using the rotating X ray tube referring to the circulation time. With this method, stenotic lesions of the coronary arteries and collateral pathways were easily observed simultaneously with morphological changes in a 180 degrees arc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307565 TI - [Left atrial ejection performance in heart failure as assessed by transesophageal Doppler echocardiography]. AB - To investigate the left atrial ejection performance in heart failure, we observed both the transmitral (TMF) and pulmonary venous flow waves (PVF) by transesophageal Doppler echocardiography in 20 patients with heart failure (16 males, 4 females, 56 +/- 13 years old). In 7 of 20 patients, pulmonary capillary wedge pressures (PC) were also obtained within 72 hours after the transesophageal Doppler echocardiographic examinations. A reversal flow on PVF during atrial systole (atrial backward ejection flow) was observed in all of the 20 patients. Corrected atrial pre-ejection period correlated significantly with PC (r = -0.76, p < 0.05), indicating that the period was shortened in accordance with left atrial Starling's law. This period correlated significantly with both the duration and the time velocity integral of atrial backward flow (r = -0.72, p < 0.005; r = -0.55, p < 0.05, respectively), but not with the atrial ejection time nor with the time velocity integral of atrial systole. These results suggest that in some cases of heart failure, left atrial contractile function is preserved despite the marked augmentation of left atrial afterload, resulting in a decrease of the left atrial forward ejection and an increase of the left atrial backward ejection. Thus, the observations of TMF and PVF by transesophageal Doppler echocardiography are useful for assessing the left atrial ejection performance in patients with heart failure. PMID- 1307566 TI - [Anthracycline cardiotoxicity evaluated by digitized M-mode echocardiography]. AB - Ten patients with malignant diseases whose mean age was 20.0 +/- 13.2 years received anthracycline derivatives therapy and were evaluated for their left ventricular systolic and diastolic functions by computer-assisted digitized M mode echocardiography. Fractional shortening (%FS), a parameter of systolic function, was measured. The first derivative of left ventricular dimension change (peak LV dD/dt), posterior wall thinning (peak LVPW thinning rate) and interventricular septum thinning (peak IVS thinning rate) were used as indices of diastolic function. Blood pressure (BP) was measured noninvasively at the end of the echocardiographic examination and hemoglobin concentration (Hb) was measured on the same day. These examinations were performed immediately before administration of anthracycline and one week and one month after the last administration. Statistical analyses were performed using the Student's t-test. The mean BP, HR, LVDd, LVDs, LVPW and IVS remained unchanged following the drug administration. %FS did not change significantly; 36.8 +/- 6.3%, before the administration, 35.3 +/- 6.5%, one week after the administration, and 36.5 +/- 5.1%, one month after the administration. Peak LVdD/dt and the peak LVPW thinning rate decreased appreciably from 4.46 +/- 1.10 to 3.76 +/- 1.08, and from 7.99 +/- 1.55 to 6.41 +/- 1.04, respectively, one week after the administration. The peak IVS thinning rate decreased from 3.54 +/- 0.81 to 2.99 +/- 0.79 after one week (p < 0.01). All of these values returned to the control levels in one month after the drug administration. We concluded that the indices of left ventricular diastolic function were more sensitive for detecting cardiac impairment than those of systolic function during the course of anthracycline therapy. PMID- 1307567 TI - [Ischemic myocardial injury evaluated using positron emission tomography in children with coronary artery disease: comparison with thallium-201 SPECT]. AB - Regional myocardial perfusion and glucose metabolism were evaluated by positron emission tomography (PET) in children with coronary artery disease. Also, PET findings were compared with those of thallium-201 myocardial single photon computed tomography (SPECT). The study patients consisted of 11 children ranging in age from 3 to 14 years. Ten patients had significantly stenotic coronary arterial lesions due to Kawasaki disease, and one patient had a left coronary artery with an anomalous origin from the pulmonary artery. Evaluation was made before and after surgical revascularization in 3 patients. Regional myocardial perfusion was assessed at rest using 13N-ammonia, and regional myocardial glucose metabolism was assessed at rest under fasting conditions using 18F fluorodeoxyglucose (18FDG). SPECT was performed after dipyridamole infusion. Initial and delayed images were obtained 7 min and 3 hrs after dipyridamole infusion, respectively. Left ventricular myocardial images were categorized as the septal, anterior, lateral, apical, and inferior segments, and evaluation was made for each segment. A total of 70 myocardial segments in 11 patients were classified into 4 groups according to the PET findings: 1) segments with normal perfusion and without enhanced 18FDG uptake (normal segments; n = 55), 2) normal perfusion with enhanced 18FDG uptake (metabolically abnormal segments; n = 3), 3) hypoperfusion with enhanced 18FDG uptake (ischemic but viable segments; n = 9), and 4) hypoperfusion without enhanced 18FDG uptake (non-viable segments; n = 3). On SPECT, the numbers of myocardial segments showing no perfusion defects, complete redistribution, incomplete redistribution, and persistent perfusion defects were 38, 12, 14, and 6, respectively. Comparisons were made between PET findings and SPECT findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307568 TI - [The effect of propranolol on the myocardial force-length relationship in the in situ canine left ventricle]. AB - The effect of beta-adrenoceptor blockade on the wall performance of the in situ canine left ventricle (LV) was evaluated based on the LV end-systolic force diameter (Fes-Des) relation in 10 healthy mongrel dogs. LV diameter was measured with ultrasonic crystals, and LV pressure was measured with a micromanometer. Preload was altered by inferior vena caval (IVC) occlusion. In the control contractility state, the IVC was occluded for 7 sec. Blockade of the cardiac beta adrenergic nerves was induced with 2 mg/kg propranolol i.v.. Slopes (Ec) and extrapolated diameter intercepts (D(o)) of the LV Fes-Des relation were obtained from end-systolic data of the control contractility state and after the infusion of propranolol. Ec was used as an index for the inotropic state of the myocardium of the LV wall. IVC occlusion during 7 sec under the control contractility state produced little change in the heart rate. Thus, IVC occlusion for 7 sec avoided the major reflex change of autonomic tone. After the infusion of propranolol, the heart rate and Ec both decreased by 24 and 43% of the control value, respectively; whereas, D(o) was not significantly altered. Therefore, it was suspected that the cardiac beta-adrenergic nerve played an important role in maintaining myocardial contractility state of the in situ canine LV wall. PMID- 1307569 TI - [Cardiac and plasma catecholamine response to dynamic exercise in hyperthyroidism]. AB - To investigate cardiac and sympathoadrenal responses to dynamic exercise, heart rate, systolic blood pressure, serial plasma norepinephrine (NE) and epinephrine (E) concentrations during multistage treadmill exercise were measured in 24 hyperthyroid patients (mean age; 42 +/- 16) and 24 age-sex matched control subjects. Eleven patients were re-examined in the euthyroid state after antithyroid therapy. Exercise duration was shorter in patient with hyperthyroidism. Also, the heart rates and systolic blood pressures at rest and in the early stage of exercise were significantly higher in hyperthyroidism. NE at rest (normal vs hyperthyroid: 124 +/- 10 vs 80 +/- 7 pg/ml, p < 0.01) and NE at peak exercise (475 +/- 38 vs 310 +/- 38 pg/ml, p < 0.01) were lower in hyperthyroidism. E at rest (22 +/- 2 vs 29 +/- 4 pg/ml, n.s.) did not differ, however, E during the first stage of exercise (30 +/- 3 vs 69 +/- 12 pg/ml, p < 0.01) was higher in hyperthyroidism. Re-examination for the euthyroid state revealed the decreases in the heart rates and systolic blood pressures at rest and in the early stage of exercise, and the normalization of the NE and E response. Thus, patients with hyperthyroidism was in the hyperdynamic cardiac state at rest and during dynamic exercise, which was accounted for by decreased sympathetic nervous activity and increased adrenomedullary responses. These modifications of sympathoadrenal response seemed reversible when patients were controlled by antithyroid therapy. PMID- 1307570 TI - [Left ventricular behavior following acute right ventricular pressure overload: an experimental study]. AB - Relationships between biventricular pressures, left ventricular shape and paradoxical septal motion in patients with right ventricular pressure overload (RVPO) are unknown. To clarify these relationships, we measured left and right ventricular short-axis dimensions and ventricular pressures using anesthetized open-chest dogs with pulmonary embolizations. With repeated microembolization, right ventricular systolic pressure (RVSP) increased stepwise from a level of 27 mmHg to the maximum value of 72 mmHg. This elevation caused gradual leftward shift of the interventricular septum (IVS) both at end-diastole and end-systole. Further embolization caused collapse (shock: left ventricular systolic pressure: LVSP < 70 mmHg) with a fall in RVSP. In the state of shock, the rise in right ventricular end-diastolic pressure (RVEDP) and fall in left ventricular end diastolic pressure (LVEDP) were prominent, and the degree of shift of the IVS became significantly greater at end-diastole than at end-systole, resulting in paradoxical motion of the IVS. There were significant linear relationships between the degree of end-diastolic IVS displacement and end-diastolic transseptal pressure (LVEDP-RVEDP), and between the degree of end-systolic IVS displacement and end-systolic transseptal pressure (LVESP-RVESP) throughout the course of repeated pulmonary microembolization even in the state of shock. In conclusion, abnormal movements of the IVS in RVPO patients indicate the presence of a marked decrease in end-diastolic transseptal pressure due to right ventricular failure. PMID- 1307571 TI - [Left ventricular function assessed by multigated blood pool single photon emission computed tomography with 99mTc]. AB - To evaluate the usefulness of gated blood pool single photon emission computed tomography with 99mTc (gated SPECT) for assessing left ventricular function, we performed gated SPECT in 2 normal subjects and 18 patients including 13 with ischemic heart disease, 3 with hypertrophic cardiomyopathy and 2 with dilated cardiomyopathy. Left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF) and regional wall motion obtained by gated SPECT were compared with the results of contrast left ventriculography (contrast LVG), echocardiography and planar multigated blood pool imaging (planar blood pool). After the patients' red blood cells were labelled with 30 mCi (1,110 MBq) 99mTc in vivo, gated SPECT was performed in each of 32 projections through a 360 degree arc for each of the cardiac cycle divided into 16. From these images, the left ventricular vertical long-axis image, the horizontal long-axis and short-axis images were reconstructed. To calculate LVEDV, we used serial short-axis images which were composed of the left ventricle. To define left ventricular and left atrial borders, we used amplitude images and cinematic displays of the vertical long-axis image. The level of the optimal cut for delineating the left ventricular border was determined from the volume-cut-level-graph at each background activity, which was constructed by a phantom study. Left ventricular wall motion by gated SPECT was compared with the results of contrast LVG according to segmental analysis. LVEDV obtained by gated SPECT showed an excellent linear correlation with LVEDV calculated by echocardiography (r = 0.98, p < 0.01) and by contrast LVG (r = 0.89, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307572 TI - [Trial assessment of pain threshold]. AB - To elucidate the pathological aspects of silent myocardial ischemia, we studied 24 patients with ischemic heart disease who had culprit lesions in the left anterior descending artery (LAD). We determined the presence of myocardial ischemia and measured coronary wedge pressures (CWP; mmHg) and collateral circulation and ST deviation on the ECG (intracoronary ECG: ic-ECG, and surface ECG; mm) after balloon inflation during PTCA intervention. The study subjects included 9 with exertional angina, 10 with post-infarction angina, and 5 with Cohn type II angina. During 78 balloon inflations, the group of ischemic symptoms (Group S) occurred in 40% of all cases, the group without ischemic symptoms (Group A) constituted 45%, and the Cohn type II specific for ischemic symptoms accounted for 15%. The relationship between CWP (X-axis) and ST deviation (Y axis) of ic-ECG was: Y = -0.46X + 20.19 (r = -0.59; p < 0.01), and the relationship between CWP and ST deviation of the surface ECG was: Y = -0.12X + 6.58 (r = -0.42; p < 0.01). Thus, a negative correlation was confirmed between them. Furthermore, similar results were obtained for Groups S and A. Based on this relationship, the pain threshold was estimated. In Group S, CWP exceeded 34 mmHg, i.e., ischemia was expected to be mild because of good collateral circulation, but an average ST deviation accompanying ischemic symptoms was observed. However, in Group A, CWP was less than 24 mmHg, i.e., ischemia was expected to be severe due to poor collateral circulation, but an average ST deviation lacking ischemic symptoms was observed. Comparison of these results showed that the pain threshold observed from the ST deviation of ic-ECG was 6.0 6.5 mm and that of the surface ECG was 2.6-2.8 mm. From these threshold values, the ST deviations during 12 balloon inflations in the Cohn type II were evaluated. Because 100% of ic-ECG and 75% of surface ECG exhibited values exceeding the threshold values, it was concluded that the cause of the Cohn type II was an increase of the pain threshold. ST deviations of the ic-ECG for Group S and the Cohn type II were 12.0 +/- 6.7 and 9.8 +/- 2.7 mm, respectively, and ST deviations of the surface ECG were 4.7 +/- 2.4 and 3.5 +/- 1.7 mm, respectively. Since there were no significant differences between Group S and the Cohn type II, it was concluded that the ischemic degree of the Cohn type II was approximately the same as that of Group S. PMID- 1307574 TI - [Complications of emergency coronary angioplasty for acute myocardial infarction]. AB - To assess the incidence and consequences of complications occurring during emergency percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI), we studied 347 patients who underwent PTCA within 24 hours after the onset of AMI. Acute occlusion occurred in 29 patients (8.4%), of whom 16 patients underwent successful repeat PTCA. All of them survived until hospital discharge. The in-hospital reocclusion rates of these 16 patients were comparable to those of patients who had not experienced acute occlusion (18.8 vs 12.8%, ns). In the remaining 13 patients, reperfusion were not successful after acute occlusion, and 6 died. Side branch occlusion occurred in 21 patients (6.1%). Left circumflex artery occlusion occurring during PTCA for the proximal left anterior descending artery was fatal in 3 patients. Right ventricular branch occlusion during PTCA for the middle of the right coronary artery resulted in intractable right ventricular infarction in one patient, and he died. Among 14 patients who underwent repeat angiography, 13 had a patent side branch which had been occluded during PTCA. One patient had coronary rupture and died. During PTCA of the proximal left anterior descending artery, acute occlusion of the artery without reperfusion or occlusion of the left circumflex artery was often fatal. However, the prognosis of acute occlusion was relatively good, if repeat PTCA was successful and most of the occluded side branches remained patent in the chronic state. PMID- 1307573 TI - [Secretion of atrial natriuretic peptide during artificial pacing: assessments including the influence of ventriculoatrial conduction]. AB - Secretion of atrial natriuretic peptide (ANP) depends on the atrial wall distension which may be caused by ventricular pacing. This study was designed to assess the differences in plasma ANP level between DDD and VVI pacing. We measured ANP from venous blood samples using radio-immunoassay in patients with the sick sinus syndrome (n = 8) and atrioventricular block (n = 2) following DDD implantation. Measurement was made under control conditions during DDD and 15-180 min after the pacing mode was changed to VVI and 60 min after returning to DDD. Serum epinephrine (E), norepinephrine (NE), renin (R) and aldosterone (A) levels were also measured prior to and every 30 min after pacing mode changes. The plasma ANP concentration changed from 71.3 pg/ml (normal value) with DDD to 126.8 (15 min), 180.6 (30 min), 221.8 (60 min), 219.2 (90 min), 270.1 (120 min), 145.4 (150 min) and 115.1 pg/ml (180 min) with VVI. It increased markedly, then gradually decreased. It returned to the control value (66.6 pg/ml) in 60 min with DDD, and it reached the peak level with VVI within 60-120 min, and the peak was significantly higher than that for DDD. The increase related to the retrograde ventriculoatrial conduction during VVI pacing. There was no significant change in the NE, E, R and A concentrations. Systolic blood pressure decreased 15 mmHg in VVI and returned to normal by DDD. These results indicated that plasma ANP levels is elevated by VVI pacing, though it was not explained by ventricular pacing alone. PMID- 1307575 TI - [Possible pathogenesis of giant negative T and negative U waves in hypertrophic cardiomyopathy: a report of two cases]. AB - Giant negative T (GNT) and negative U (NU) waves are electrocardiographic findings which have been frequently observed in hypertrophic cardiomyopathy (HCM). Here we report 2 cases. For the first patient, electrocardiographic and left ventriculographic studies before and after the development of GNT and NU waves and left ventricular high voltage during the follow-up period were performed. For the second patient, electrocardiographic and echocardiographic findings were obtained before and after onset of posterior myocardial infarction. In the first patient, posterior papillary muscle hypertrophy was evident on left ventriculography after appearance of GNT and NU waves. In the second patient, both GNT and NU waves disappeared after posterior myocardial infarction. Two dimensional echocardiograms demonstrated akinesis in the posterior wall, including the posterior papillary muscle, after 8 weeks of posterior infarction. Therefore, we suggest that apical hypertrophy, especially of the posterior papillary muscle, may play an important role in the pathogenesis of GNT and NU waves in HCM. PMID- 1307576 TI - [Myocardial perfusion and left ventricular function during exercise evaluated by 201Tl myocardial scintigraphy and 99mTc radionuclide ventriculography in patients treated with PTCA]. AB - To evaluate the effects of percutaneous transluminal coronary angioplasty (PTCA), we investigated myocardial ischemia and left ventricular function during exercise before and after successful PTCA in 30 patients. We used extent and severity scores of 201thallium (201Tl) exercise myocardial scintigraphy to assess myocardial ischemia and determined global and regional left ventricular ejection fraction (EF and REF) of 99mTc-RBC exercise radionuclide ventriculography to assess left ventricular function. The extent and severity scores of stress images were significantly less after PTCA than before PTCA. The scores of the redistribution images were unchanged before and after PTCA. Global EF during exercise was significantly higher after PTCA than before PTCA. There was no difference in resting global EF between before and after PTCA. Myocardial ischemia induced by exercise was semi-quantitatively analyzed as transient perfusion defect with severity score. Severity score was significantly less after PTCA than before PTCA. delta EF, which was obtained by subtraction of resting global EF from exercise one, was significantly higher after PTCA than before PTCA. However, the degree of improvement in myocardial ischemia and left ventricular function varied from patient to patient. In 17 patients with one vessel left anterior descending artery disease, delta REF, which was determined by subtracting resting regional EF from exercise one, was significantly higher in septal and apical segments after PTCA than before PTCA. Myocardial ischemia and left ventricular function under exercise were alleviated by PTCA. However, the degree of improvement varied from patient to patient and it might have been affected by various factors including coronary dissection, edema, thrombus, restenosis, spasm, side branch stenosis or occlusion, distal thrombus, and myocardial hibernation. PMID- 1307577 TI - [Continuous monitoring of coronary venous oxygen saturation during PTCA and its relation to electrocardiographic ST changes]. AB - The purpose of this study was to investigate change in coronary venous oxygen saturation (CSO2-Sat) during percutaneous transluminal coronary angioplasty (PTCA) and to compare the results with those of standard 12-lead ECGs (s-ECG) and epicardial ECG induced using an intracoronary guidewire (ic-ECG). CSO2-Sat was measured continuously in 10 patients undergoing PTCA; 5 patients with lesions in the left anterior descending coronary artery (LAD), one with lesions in the left circumflex artery (LCX), and 4 with right coronary artery (RCA) lesions. The results were as follows: 1. In all 6 patients with stenotic lesions in the left coronary artery, CSO2-Sat decreased by 5 to 22% immediately after balloon inflation. Significant changes in ic-ECG (ST deviation > or = 0.1 mV) were observed in 5 of the 6 patients, while significant changes in s-ECG (ST deviation > or = 0.1 mV) were observed in only 3 of the 6 patients. The s-ECG did not seem to be sensitive enough to represent myocardial ischemia in the LCX. 2. The interval from the balloon inflation to the significant change was shorter for CSO2-Sat than for the ECGs in 4 of the 5 patients with LAD lesions, except Case 4. The recovery time of CSO2-Sat to the basal level on balloon deflation was longer than the recovery times of ic-ECG and s-ECG. 3. There was no significant change in the CSO2-Sat in 3 of the 4 patients undergoing PTCA for RCA lesions, while significant changes were observed in the ic-ECG and s-ECG in all 4 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307578 TI - [Assessment of prognosis of old myocardial infarction]. AB - In an attempt to predict high risk myocardial infarction, we studied 201 patients with Q wave infarction with dipyridamole-loading thallium-201 myocardial perfusion scintigraphy (D-MPS), left ventriculography, coronary angiography and treadmill exercise testing. The results of these tests were related to the use of initial PTCA or CABG, and the occurrence of cardiac deaths and nonfatal cardiac events during a mean follow-up period of 39 months. Three high risk parameters were identified by D-MPS; partial redistribution, diffuse slow washout, and extensive fixed defects. The patients were categorized into 3 groups according to the numbers of high risk parameters: group A (n = 50), patients with 2 or more high risk parameters; group B (n = 95), patients with one high risk parameter; group C (n = 56), patients without a high risk parameter. The prevalence of 3-, 2 , and one- or insignificant vessel disease was 72, 20 and 8% in group A, 15, 16, and 69% in group B, and 5, 13 and 82% in group C, respectively. Initial PTCA or CABG was performed in 42% of the patients in group A, 5% of the patients in group B, and 2% of the patients in group C. Among medically-treated patients, cardiac deaths occurred in 31% in group A, 4% in group B, and in none in group C. Nonfatal cardiac events occurred in 24, 12, and 4%, respectively. Coronary angiography revealed 3-vessel disease in 53 patients, 2-vessel disease in 32, and one-vessel disease or insignificant lesions in 116 patients. Initial PTCA or CABG was performed in 45% of the patients with 3-vessel disease, 6% of those with 2 vessel disease and 1% of those with one-vessel disease. Among medically-treated patients, cardiac deaths occurred in 31% with 3-vessel disease, 7% with 2-vessel disease, and in 2% with one-vessel disease. Nonfatal cardiac events occurred in 17, 10, and 3%, respectively. PMID- 1307580 TI - [Clinical and echocardiographic evaluation of the effects of atrial defibrillation in patients with idiopathic cardiomyopathy]. AB - To elucidate the effects of atrial defibrillation in patients with idiopathic cardiomyopathy, we clinically and echocardiographically assessed 6 patients with hypertrophic cardiomyopathy (HCM) and 7 patients with dilated cardiomyopathy (DCM). Their mean age was 57 +/- 14 years and the mean duration of their atrial fibrillation (Af) was 47 +/- 29 days. There were no differences in age and the duration of Af between the HCM and DCM groups. We assessed the effects of defibrillation on the NYHA functional classification, heart rate (HR), systolic blood pressure (S-BP), M-mode echocardiographic data (LVDd, LVDs, %FS, LAD) and transmitral pulsed Doppler echocardiographic findings (peak velocity, time velocity integral of rapid and atrial filling waves). These indices were obtained before and 52 +/- 22 days after defibrillation, and were compared with each other. 1. HR decreased (HCM: 87 +/- 16-->58 +/- 7/min, DCM: 93 +/- 19-->70 +/- 14/min) and total left ventricular filling increased (HCM: 6 +/- 1-->11 +/- 4 cm, DCM: 6 +/- 1-->10 +/- 2 cm) after defibrillation, and the increment of %FS (HCM: 36 +/- 6-->41 +/- 6%, DCM: 16 +/- 6-->25 +/- 11%) was observed. Four of 6 HCM patients and 5 of 7 DCM patients also improved with regard to the NYHA classification. 2. After defibrillation, LVDd increased in HCM (42 +/- 4-->47 +/- 4 mm), but not in DCM. However, LVDs decreased in DCM (52 +/- 9-->44 +/- 12 mm), but not in HCM. We concluded that atrial defibrillation had a beneficial effect on the recovery of the left ventricular function both in HCM and DCM due to the reduction in HR and increase in left ventricular filling. The mode of LV functional improvement after defibrillation varied depending on the state of patient's basal pathophysiology . PMID- 1307579 TI - [Clinical features of latent dilated cardiomyopathy]. AB - To identify the evidence of presymptomatic manifestations of dilated cardiomyopathy (DCM), we studied 30 patients with latent DCM (mean 37 +/- 14 years) who satisfied the following criteria: 1) left ventricular (LV) systolic function was slightly reduced; 2) LV end-diastolic dimension (< 54 mm) and coronary arteries were normal. The incidence of ECG abnormalities was relatively high; nonspecific ST-T changes were the most common (90%). The incidence of grade 3 or 4 ventricular premature contractions according to Lown's classification on 24 hour ambulatory ECGs was 50%. Perfusion defects were observed in 83% on the thallium-201 images. Right ventricular biopsy showed that the interstitial fibrosis was milder (9 +/- 9%) in the study subjects than in 32 patients with DCM (17 +/- 8%) who were treated in our hospital, but there were no significant differences in the diameters of the myofibers (15 +/- 4 vs 17 +/- 4 microns) between the 2 groups. During the follow-up study, deterioration of LV dysfunction was observed in 3 patients. One patient died suddenly. These findings proved the importance of the early detection and characterization of latent state of DCM. PMID- 1307581 TI - [Left ventricular trabeculae evaluated with MRI in dilated cardiomyopathy and old myocardial infarction]. AB - The morphological examination of the left ventricular trabeculae was performed using MRI (0.5T) in 14 normal volunteers, 12 patients with dilated cardiomyopathy (DCM), and 9 patients with old myocardial infarction (OMI). Left ventricular trabeculae were observed at the free walls of the left ventricle in all subjects, but not at the septal wall. Left ventricular trabeculae were larger in DCM than in the normals. The trabeculae were scarce in OMI and inner sides of the infarcted myocardium were very smooth. The development of the left ventricular trabeculae was graded as diminished, ordinary, and marked. Ordinary trabeculae were seen in 86% of the normals, whereas; marked trabeculae in 75% of DCM, and diminished trabeculae in 78% of OMI. In patients with DCM, the mean area of the left ventricle with marked trabeculae was greater than that with ordinary trabeculae. The more dilated left ventricle, the thinner the anterior wall was and the lower the ejection fraction was in DCM and OMI, though there were no significant differences in values of these 3 items between DCM and OMI. The MRI findings on the development of the trabeculae were confirmed in patients with DCM at autopsy. Thus, the MRI findings were very useful in the differential diagnosis between DCM and OMI. PMID- 1307582 TI - [Late potentials in dilated cardiomyopathy in relation to ventricular tachycardia and cardiac function: their significance]. AB - We assessed the usefulness of ventricular late potentials (VLP) for detecting ventricular tachycardia (VT), and of the relationship between VLP and left ventricular dysfunction. The subjects consisted of 21 patients with dilated cardiomyopathy (DCM) not accompanied with ventricular conduction disturbances. Signal-averaged electrocardiograms were recorded by using VCM-3000. The signals of 200 or more beats were averaged through the 40-300 Hz band-pass filter until the noise level was reduced to less than one microvolt (microV). The duration (fQRSd) and the root mean square voltage (LP40) for the last 40 msec of the filtered QRS complex were calculated. The left ventricular diastolic dimension (LVDd), systolic dimension (LVDs) and the ejection fraction (EF) were obtained by echocardiography. Five of 21 patients had VT. fQRSd was significantly longer in patients with VT than in those without VT (158.8 +/- 8.6 vs 126.5 +/- 10.4 msec, p < 0.01). LP40 was significantly less in patients with VT than in those without VT (8.7 +/- 2.7 vs 24.1 +/- 12.3 microV, p < 0.01). If the presence of "fQRSd > or = 120 msec" or "LP40 < or = 20 microV" was defined as VLP positive, as in patients with old myocardial infarction, the criteria sensitivity was 100% and their specificity was 25% for detecting VT. If the presence of both "fQRSd > or = 135 msec" and "LP40 < or = 20 microV" was defined as VLP positive, the criteria sensitivity was 100%, and their specificity, 88%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307583 TI - [Left atrial booster pump function in patients with hypertrophic cardiomyopathy and essential hypertension: evaluations based on left atrial pressure-volume relationship]. AB - In patients with hypertrophic cardiomyopathy (HCM) and essential hypertension (HT), left ventricular dysfunction in early diastole which is associated with left atrial contraction plays an important role in left ventricular filling. To evaluate left atrial booster pump function, we analyzed left atrial preload (left atrial pressure at the end of diastasis; LAPd, left atrial volume index at the end of diastasis; LAVd), left atrial afterload (left ventricular end-diastolic pressure; LVEDP, left ventricular chamber stiffness constant; K), and left atrial ejection indices (left atrial ejection fraction during atrial contraction; LAEF, left atrial ejection volume index during atrial contraction; ACVI). The study subjects consisted of control subjects (n = 5), HT patients (n = 6), and HCM patients (n = 11). The left ventricular wall was significantly thicker in the HT and HCM groups. The left ventricular rapid filling volume index was less in the HT group, and significantly less in the HCM than in the control group. LAPd and LAVd were greater in the HT group than in the control group, and greater in the HCM group than in the HT group. LVEDP and K were greater in the HT group than in the control group, and significantly greater in the HCM group than in the other 2 groups. ACVI was greater in the HT group than in the control group, but in the HCM group, ACVI was significantly less than in the HT group and did not differ significantly from that in the control group. LAEF was significantly less in the HCM group than in the other 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307584 TI - Could AIDS retard India's development? PMID- 1307585 TI - A comparative study of flurbiprofen and piroxicam in osteoarthritis. AB - In this single-blind, multiple-dose study the efficacy and tolerability of flurbiprofen was compared with that of piroxicam in 60 adult patients suffering from osteoarthritis of the knee. The patients were randomly allocated to receive either flurbiprofen 100 mg twice daily or piroxicam 20 mg once daily for a period of four weeks. Clinical assessments w.r.t. pain, tenderness, stiffness, swelling and general activity of patient were carried out prior to initiation of trial therapy and thereafter at weekly intervals for four weeks. The findings were graded. Though significant improvements as compared to baseline data occurred in both the treatment groups, flurbiprofen was found to be superior to piroxicam in improving pain on movement and at rest (p < 0.05). The incidence of side effects was less in the group receiving flurbiprofen (6% compared to 47% observed with piroxicam). PMID- 1307586 TI - Study of intrarenal vasculature in cases of primary and secondary hypertension (by metallic impregnation technique on whole kidney section) AB - Study of intrarenal vasculature was carried out by using the metallic impregnation technique on whole kidney sections in 31 [corrected] cases of (primary and secondary) hypertension and 10 normal controls. Distinct patterns of intrarenal vasculature were noted in controls and in cases of hypertension. Gradual tapering of vessels, absence of tortuosity and good peripheral vascularisation were noted in controls. Abrupt tapering, tortuosity of vessels and poor peripheral vascularisation were noted in hypertensive cases. In essential hypertension moderate to severe changes of dilatation of the segmental and/or arcuate arteries was noted. The degree of dilatation was related to the level of systolic BP rather than diastolic in cases of essential hypertension. Secondary hypertension even if severe, rarely showed significant dilatation lesions. Avascular zones and conglomeration of vessels at poles was seen only in cases of pyelonephritis. This helped in distinguishing these, from cases of glomerulonephritis. PMID- 1307587 TI - What should be called a brisk 'Y' descent? AB - Patients with pericardial constriction show a prominent 'y' descent in right atrial and vena caval pressure traces. In all earlier hemodynamic descriptions of constrictive pericarditis, the 'y' descent has been described as 'brisk', 'sharp' or 'rapid' but no effort has been made to quantify the same. In this study, we have tried to objectively evaluate and describe this 'y' descent by measuring its negative slope (-dy/dt) at its steepest portion. Forty one patients were studied hemodynamically, 9 with constrictive pericarditis (Group I) and 32 normals (Group II). The negative slope of the 'y' descent in patients with constrictive pericarditis (69.95 +/- 23.04 mm Hg) was found to be significantly greater than normals (35.13 +/- 7.84 mm Hg, p < 10(-6). Discriminant analysis was used to determine its sensitivity, specificity, predictive value and overall accuracy, in the diagnosis of pericardial constriction. Value of > or = 45 mm Hg/sec was found to have the highest overall accuracy (0.88). The correlation between the right ventricular end diastolic pressure and the slope of 'y' descent in patients with pericardial constriction (r = 0.66) and in normals (r = 0.60) was fair. It is concluded that -dy/dt is significantly different in patients with constrictive pericarditis as compared to normals. The diagnostic utility of this parameter needs to be evaluated in patients with equivocal clinical and hemodynamic data, in those with occult pericardial constriction and in post-pericardiectomy cases where the pressures do not normalise immediately after adequate pericardial resection. PMID- 1307588 TI - Craniopharyngioma: treatment by conservative surgery and radiation therapy. AB - Benign neoplasms are curable only when excised. This applies even to craniopharyngiomas. The proximity of craniopharyngiomas to the hypothalamus and neurovascular structures makes total excision difficult to achieve. Over the last 3-4 decades, it has become increasingly obvious that craniopharyngiomas respond to radiation therapy. Early, unhappy results with major excisions have prompted us to adopt a policy of conservative surgery and radiation therapy to the residual tumour. Preliminary results suggest a good outcome in 35 of the 63 patients so treated from 1981. Details of the study are presented. PMID- 1307589 TI - Wildervanck syndrome (cervico-oculo-acoustic syndrome). AB - Wildervanck syndrome i.e. cervico (Klippel-Feil anomalad) -oculo (Duane-Stilling Turk phenomenon with bilateral abducens palsy)-acoustic (deafness) is a rare syndrome. We report here 4 cases diagnosed as Wildervanck syndrome and analyse their findings. One patient had an an atrial septal defect. Such association of congenital heart disease with Wildervanck syndrome has not been reported previously. PMID- 1307590 TI - Relevance of plasma fibrinogen estimation in obstetric complications. AB - We present a study of fibrinogen levels in 133 patients who were prone to develop disseminated intravascular coagulation as a result of an underlying complication of pregnancy such as abruptio placentae, pregnancy-induced hypertension, missed abortion, septic abortion, intrauterine fetal death, vesicular mole and amniotic fluid embolism. A high incidence of hypofibrinogenemia was found in cases of abruptio placentae (43.9%) and pregnancy-induced hypertension (25%). Hypofibrinogenemia occurred in 10% cases of intrauterine fetal death within 4 weeks of fetal demise. The use of this simple investigation makes possible the diagnosis of hemostatic failure and also helps to guide replacement therapy during the fibrinopenic state. There were 4 maternal deaths and 12 perinatal losses in this study. PMID- 1307591 TI - Disseminated intravascular coagulation: a review with experience from an intensive care unit in India. PMID- 1307592 TI - Hydatid cyst of the tibia. AB - A case of hydatid cyst of the tibia, which manifested as a pathologic fracture is being reported. Pain and swelling of left lower limb with inability to bear the weight were the main features. Tender swelling was also noted at the upper and middle third of tibia. Open biopsy revealed the hydatid cyst wall and scolices of Echinococcus granulosus. Albendazole treatment was followed by curettage and bone grafting. PMID- 1307593 TI - Epithelioid sarcoma of the upper extremity with cerebral metastases. AB - A forty year old male patient presented with swollen, deformed right hand with multiple irregular ulcers. The axillary lymph nodes were enlarged, firm and tender. The biopsy of nodules present on the hand revealed areas of haemorrhage and necrosis. The histopathological examination confirmed the clinical diagnosis of epithelioid sarcoma. Following below-elbow amputation, patient failed to regain consciousness and expired. On autopsy, distant metastases were found in the regional lymph nodes, pleura, kidney and cerebrum. PMID- 1307594 TI - Use of aminocaproic acid (ACA) in extra-amniotic MTP in patients on anti coagulant therapy. AB - A case of rheumatic heart disease (RHD) with prosthetic mitral valve endocarditis receiving anticoagulation with heparin, underwent medical termination of pregnancy in a second trimester. The following report entails the use of aminocaproic acid (ACA) in preventing excessive bleeding during and after the procedure, while the patient continued to receive anticoagulant therapy. PMID- 1307595 TI - Orbital cysticercosis. AB - Orbital cysticercosis is a rare condition. We report here 3 cases with orbital cysticercosis who presented with proptosis and ptosis (Case no. 1 and 2) and focal seizures (Case no. 3). All of them had a vision of 6/6. Diagnosis of cysticercosis was made on CT Scan. The lesions isolated in Cases 1 and 2 and were excised. Drug therapy was given to treat any persisting infestation. Case no 3 had multiple brain cysticerci in addition to the orbital one. However, the patient was lost to follow-up. PMID- 1307596 TI - Pulmonary metastases on bone scan in a patient with osteogenic sarcoma. AB - This paper describes a young man who was treated with amputation for osteogenic sarcoma of the lower end of the right tibia. Pre-operative whole body bone scan with 99 mTc did not reveal abnormal tracer concentration in the lungs. A similar follow-up bone scan six months post-operatively demonstrated an area of abnormal tracer concentration in the lower lobe of each lung. PMID- 1307598 TI - Cytodiagnosis for pelvic tuberculosis. AB - A 25 yr old married woman with complaints of lower abdominal pain for 2 months, was found to have a irregular nontender mass in pelvis, adherent to uterus. Her Papanicolaou smear was inflammatory. To confirm the diagnosis of either ovarian malignancy or pelvic tuberculosis made on the basis of observations during exploratory laparotomy, ovarian biopsy was taken. The imprint cytodiagnosis was tuberculosis. The patient was then managed surgically and the previous diagnosis was reconfirmed by histopathology. Imprint cytodiagnosis appears to be a valuable technique whenever facilities for frozen section are not available. PMID- 1307597 TI - Insulinoma. AB - A case of insulinoma who had episoic bizarre behaviour is presented here. Pre operative fasting and two hour post-prandial blood sugar values indicated hypoglycemia with inappropriately high insulin levels. USG and CT scan of the abdomen revealed a tumor of head of the pancreas. The tumour was enucleated surgically. Histopathological examination confirmed the origin as islet cells. The post-operative blood sugar and insulin levels were found to be in normal range. Since insulinoma is a rare pancreatic tumor, differential diagnoses along with a brief review of the literature is also presented. PMID- 1307599 TI - Multiple chylous cysts of abdomen causing intestinal obstruction. AB - A case of multiple chylous cysts of the abdomen in a 35 years old female is presented here. The patient presented with signs and symptoms of acute intestinal obstruction. Exploratory laparotomy revealed few intestinal adhesions along with multiple small cysts containing blood stained gelatinous material in the abdominal cavity, some of which were excised alongwith lymph nodes. The abdomen was closed after a saline peritoneal lavage. Chylous nature of the cysts was confirmed on histopathology. The post-operative course was asymptomatic. PMID- 1307600 TI - Primary extrapancreatic gastrinoma. AB - Extrapancreatic gastrinoma is a rare clinical entity encountered in surgical practice. A patient was referred to us who had a history of recurring symptoms of peptic ulcer disease and ulcer perforation located at an unusual site. Serum gastrin levels were abnormally high. Scopy revealed multiple ulcers in the antrum and duodenum. A mass superior to the head of the pancreas was detected on USG, which later on found to be a separate mass on CT scan. The tumour was excised and confirmed on histopathology. Results of conservative surgery were found to be satisfactory. PMID- 1307601 TI - The Consumer Protection Act. PMID- 1307602 TI - [Lupus anticoagulant]. AB - Lupus anticoagulant (LAC) is an acquired inhibitor of prothrombin activator complex, which probably interferes with the phospholipid portion. Characteristically, LAC prolongs the partial prothrombin time, but only slightly prolongs the prothrombin time. It is a paradoxical fact that LAC is characterized by thrombosis. It was initially described in patients with SLE, but recently, it has been described as occurring with other autoimmune disorders. Patients with LAC have been treated with steroid and aspirin, anti platelet agents or warfarin. Steroid and aspirin therapy has been reported useful for habitual abortion associated with LAC. In our study, 11 patients, whose prior pregnancies resulted in habitual abortion (41 abortions), received intentional prednisolone (40 mg/day) and aspirin (81 mg/day) therapy before further pregnancies. The doses of both agents were decreased gradually, and the therapy with prednisolone (10-15 mg/day) and aspirin (40.5 mg/day) was maintained during the pregnancy period. The outcome of pregnancy was successful in 7 out of 10 pregnancies. To evaluate the relationship between LAC and glomerulopathy, we examined the renal biopsy from 5 LAC cases without SLE. In pathological findings, there were 3 of with mild proliferative GN and 2 cases of minor glomerular abnormality. There were no characteristic findings in LAC nephropathy. PMID- 1307603 TI - [Nephritis and complement]. AB - There are many cases in which renal biopsies show glomerular complement accumulation. Some of these cases have low serum complement levels, but the extent to which the complement system participates in the pathogenesis of glomerulonephritis is unknown. We examined the activation system in acute poststreptococcal glomerulonephritis (PSGN). Ordinarily in PSGN an alternative pathway is activated. In the early stage of the disease, both C3 and C4 serum complement levels were depressed in one fourth. This suggested that the classical pathway is also activated in PSGN. Serum complement levels are very important in the diagnosis of the type and severity of lupus nephritis. Serum complement levels and activity index of lupus nephritis were very well correlated in our cases. The improvement of serum complement levels may corresponds to the improvement of the pathological activity of the disease. PMID- 1307604 TI - [Glomerulonephritis and superoxide dismutase]. AB - To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-superoxide dismutase (SOD) in glomeruli of patients with IgA nephropathy by immunohistochemistry on 37 kidney specimens consisting of 32 IgA nephropathy and normal parts of the 5 resected kidneys with renal tumors serving as controls. To evaluate the change in renal function, creatinine clearance (Ccr) was assessed at the time of biopsy and 1 year after the biopsy. In the normal kidney, Cu, Zn-SOD was localized in the tubular cells, and not in the glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD was detected on the epithelial side of the glomerular capillary wall in addition to the tubular cells. The extent of localization of this enzyme was compared with the clinical findings at the time of biopsy. When Cu, Zn-SOD was stained strongly in the glomeruli, the histological change of the glomeruli was milder, and the renal function appeared to be more preserved; the decrease in Ccr one year after the renal biopsy was inhibited. These findings suggest that Cu, Zn-SOD has beneficial actions for renal function as anti-oxidative factors. PMID- 1307605 TI - [Clinical and laboratory evaluation of pediatric kidney disease]. AB - In infancy, the kidney by itself is immature and the body fluid composition is extremely different from that in adults. Further more, there are various renal diseases in children with characteristics different from those in adults. Thus in childhood, consideration for aging is critical for evaluation of renal function, and diagnosis of the disease. Recently, mass screening for infants or children in kindergarten or school has enabled us to find many children with renal disease, in whom symptoms are not overt. Thus the disease can be treated in an early phase. This may give a better prognosis for such children. To make an early diagnosis of renal disease it is essential to consider what laboratory tests are chosen and how the data accumulated are interpreted. In the present study, individual laboratory tests for the diagnosis of renal diseases and an indication of such tests as well as interpretation of the data are reviewed. PMID- 1307606 TI - [Laboratory data in chronic dialysis patients]. AB - The principle of prescribing dialysis therapy is treatment of uremic symptoms and morbidity, and adequate therapy to prevent complication of long term dialysis. For this purpose careful measurement and monitoring of various parameters should be done in chronic dialysis patients. We analyzed the laboratory data of 82 patients treated at our dialysis center. We started correction of renal anemia with erythropoietin from 1987, and the mean hematocrit was improved from 24% to 28%. The blood transfusion volume was decreased markedly. There was a significant correlation between plasma alpha-human atrial natriuretic peptide (HANP) levels and the size of the heart. Plasma HANP seems to be a reliable parameter of the so called dry weight in patients on maintenance dialysis. We analyzed the parameters of bone for the recent four years. Alkaline phosphatase (ALP) and C-PTH increased throughout the duration of dialysis, while bone mineral density (BMD) decreased. Annual changes of sigma GS/D were negatively correlated with ALP and C-PTH. In relation to duration of dialysis, changes of sigma GS/D were less in the group treated for less than 3 years. Nine patients (60% of patients on dialysis more than 10 years) had carpal tunnel syndrome (CTS) with symptoms and signs. Median nerve distal motor latency was positively correlated with the duration of dialysis. The beta 2-microglobulin (beta 2-MG) level of dialysis patients was very high and even though the beta 2-MG level was lowered by hemodiafiltration CTS was not improved. PMID- 1307607 TI - [Laboratory tests in acute renal failure]. AB - This review is focused on the roles of laboratory test in acute renal failure (ARF). The roles of the laboratory test changes along with the alterations in clinical features and with the advances of treatment. Recent acute renal failure is characterized by the following three features: most of the ARF develops in hospitals, the frequency of nonoliguric ARF is increasing, and the association of other organ failure such as heart failure, liver failure or respiratory failure, increases the mortality rate. Hemodialysis is instituted in the early phase of ARF to enable the supply of enough nutriments and drugs. These features of recent ARF increases the importance of the frequent analysis of plasma creatinine in patients, who are at risk for ARF, to diagnose ARF at the onset. After the development of ARF, laboratory tests for the evaluation of other organ function is repeated. The development of new drugs increases the incidence of interstitial nephritis, and the advances in the therapeutic approach on systemic diseases (such as SLE or PN), which frequently develop ARF, alter the prognosis of these diseases. Since the early diagnosis of these diseases is important, it is necessary to develop noninvasive and reliable tests for the diagnosis of these diseases. PMID- 1307608 TI - [Diagnosis on Mycoplasma pneumoniae infections by DNA-probe assay in comparison with serological tests]. AB - To evaluate the usefulness of DNA diagnosis as a diagnostic approach to Mycoplasma pneumoniae infections, we compared the DNA-probe assay with serological tests in 32 patients who were clinically suspected of having Mycoplasma pneumonia. The DNA-probe assay was carried out using the Gen-probe kit. Serological tests included complement fixation and passive hemagglutination tests. At first visit 10 patients were positive for the DNA-probe assay, while only 2 of them were positive for serological tests. The other 3 patients became positive for serological tests during the clinical course. In accordance with clinical improvement, these patients became negative for the DNA-probe assay. Three patients were negative for DNA-probe assay while they were positive for the serological tests. However, these patients had already received antibiotics; therefore, their conditions were considered to have been improved at the time of the study. The other 19 patients were negative for both the DNA-probe assay and serological tests. These patients might have suffered from respiratory tract infections of pathogenic organisms other than M. pneumoniae or the number of M. pneumoniae might have been too small to be detected by the DNA-probe assay. The results of the present work demonstrate that the DNA-probe assay was valuable in the diagnosis of mycoplasmal infections at the early stage, which indicates that DNA diagnosis provides useful information to determine the most appropriate therapeutic regimen. PMID- 1307609 TI - [Genetic diagnosis of phenylketonuria: identification of the mutations of phenylalanine hydroxylase gene by PCR direct sequencing]. AB - To investigate the mutations of the phenylalanine hydroxylase (PAH) gene in Orientals, direct sequencing was conducted on DNA fragments amplified by the polymerase chain reaction, using solid phase technology involving the biotin streptavidin system. Four mutations possibly associated with phenylketonuria (PKU) were identified in a Chinese and four Japanese patients. A novel Arg158 (CGG)-to-Trp158 (TGG) mutation was identified in exon 5 of the PAH gene in a Chinese PKU patient. The second change was due to a G-to-A transversion at the last base of intron 4. The third change was a compound heterozygote; one mutation was a G-to-A transversion at the last base of intron 4. The other was a G-to-C transversion at the second base of codon 413, which resulted in a substitution of Arg(CGC) by Pro(CCC) in exon 12. The last change was due to a Tyr204(TAT) -to cys204(TGT) mutation in exon 6 of the PAH gene in two Japanese. This preliminary study revealed a novel PKU mutation and considerable genetic heterogeneity in the PAH gene among Orientals. PMID- 1307610 TI - [Detection of the mutation responsible for adenine phosphoribosyltransferase deficiency among Japanese patients]. AB - Adenine phosphoribosyltransferase (APRT) deficiency causes 2,8 dihydroxyadenine(DHA) urolithiasis and renal failure. Recently, two different common mutations were identified; one was APRT* J with a substitution of ACG for ATG at codon 136, called "Japanese-type", another was APRT* Q0 with TGA for TGG at codon 98. Approximately 98% of all Japanese patients with this disorder have been estimated to have these mutations APRT* J (approximately 80%) and/or APRT*Q0 (approximately 20%). We developed a diagnostic method to detect these genotypes. After gene amplification by PCR, target DNA was hybridized with a biotinylated specific probe in the presence of the non-labelled competitive probe on a dot blotted membrane. To detect the APRT* J (or APRT* Q0) mutation, the biotinylated APRT* J (or APRT* Q0) probe and non-labelled normal probe for the same region were used as specific and competitive probes, respectively. After incubation at 60 degrees C for 30 min, the temperature was gradually decreased from 60 degrees C to 40 degrees C during 120 min, and then incubation was continued at 40 degrees C for 30 min. By using method, we were able to omit the posthybridization process, and the detecting signal was clear and highly specific. This method is useful for detecting point mutations in other genes. PMID- 1307611 TI - [Clinical application of anti double-stranded and single-stranded DNA antibodies measurements by enzyme-linked immunosorbent assay (ELISA) using E. coli plasmid DNA]. AB - Anti double-stranded (ds) and single-stranded (ss) DNA IgG antibodies were detected in patients with various connective tissue diseases by RECOMBIGEN ELISA Anti ds-DNA Kit and ELISA Anti ss-DNA Kit (Nippon DPC Co) using E. coli plasmid DNA. High levels of anti ds-DNA and anti ss-DNA antibodies were mostly found and distributed in patients with systemic lupus erythematosus(SLE) and allied disorders. The sensitivity of Anti ds-DNA Kit was higher than that of current ELISA kit using calf thymus DNA antigen. In SLE patients with anti DNA antibodies sixty per cent of sera were reacted with both ds- and ss-DNA antigens, and forty per cent of sera were reacted only with ss-DNA antigen; there was no sample reacted positively with ds-DNA antigen alone. RECOMBIGEN ELISA Anti ds-DNA Kit and ELISA Anti ss-DNA Kit are highly sensitive and useful methods to detect anti ds- and/or ss-DNA IgG antibodies in patients with SLE. PMID- 1307612 TI - [Flow cytometric determination of active oxygen produced by neutrophils in patients with inflammatory diseases]. AB - We investigated active oxygen (H2O2) production by neutrophils in patients with inflammatory diseases such as connective tissue disease and respiratory tract infection. The analysis was done by flow cytometry using as small volume of whole blood as 100 microliters. H2O2 production as well as C-reactive protein (CRP) were increased in connective tissue diseases, and was decreased after steroid therapy. In a case of neuro-Behcet's disease, changes in H2O2 production was observed in agreement with those in clinical symptoms such as gait disturbance. H2O2 production as well as CRP and neutrophil count were increased in acute respiratory tract infection, but in chronic patients H2O2 production alone was rather reduced. In stages of enhanced H2O2 production, tissue damage or inflammation may exist, the degree of which seems to be well reflected by H2O2 production. During stages of impaired H2O2 production, care should be taken to prevent infections. Using flow cytometry, H2O2 production can be easily determined as one of functions of neutrophils. PMID- 1307613 TI - [OK-432-induced cytokines production by peripheral blood mononuclear cells]. AB - Cytokines production by OK-432-stimulated peripheral blood mononuclear cells (PBMC) were measured to investigate the in vitro function of macrophages (M phi) and lymphocytes. PBMC (1 x 10(6) cells/ml) were cultured with OK-432 (0.05 KE/ml) for 72 hr at 37 degrees C under 5% CO2, then interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and soluble IL-2 receptor (sIL-2R) levels in the culture supernatants were measured by ELISA. While there was no significant differences of IL-1 beta production between patients with chronic active hepatitis type B (CAH-B) and controls, sIL-2R production (335 +/- 219 U/ml, mean +/- SD) was significantly decreased (p < 0.001) in patients with CAH-B. On the other hand, in pregnant women, production of both IL-1 beta (6.3 +/- 3.9 ng/ml, p < 0.01) and sIL-2R (300 +/- 169 U/ml, p < 0.001) were significantly lower than those in controls (13.5 +/- 3.8 ng/ml, 969 +/- 154 U/ml). These results suggest that the expression of IL-2R alpha on lymphocytes membrane is suppressed in patients with CAH-B, and that decreased M phi function is present in pregnant women. PMID- 1307614 TI - [Studies on the fragments of FDP in 4 patients with DIC]. AB - We previously studied fibrinolysis and fibrinogenolysis by analyzing fragments of fibrin/fibrinogen degradation products (FDP) employing sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. In this report, we characterized the fragments of FDP in four patients with disseminated intravascular coagulation (DIC), that were caused by various diseases. In the patients suffering from acute lymphoblastic leukemia (case 1) and acute suppurative cholangitis (case 3), DD and DY/X fragments resulting from fibrinolysis accounted for the most part of the FDP fragments. In case 3, D fragments resulting from fibrinogenolysis were also observed to much less extent. In a DIC associated with acute myeloblastic leukemia (case 2), both fibrinolysis and fibrinogenolysis were increased and resulted in high levels of D, Y and DY/X fragments, concomitant with moderate levels of DD and high molecular weight (HMW) fragments in the patient's sera. The increased fibrinogenolysis in this case was attributed to accelerated activation of plasmin. In a DIC patient of case 4, who underwent an operation due to hepatocellular carcinoma, marked increase in DY/X and HMW fragments and slight increase in DD fragment were observed on the day of operation. Hyperfibrinolysis documented in case 4 was explained by both increased production of thrombin and moderately accelerated activation of plasmin. Both qualitative and quantitative changes in the fragments of FDP during the courses of treatment in two cases of DIC were also noted. In summary, each underlying disease expresses characteristic pattern of FDP fragments in DIC. PMID- 1307615 TI - [A new method for the determination of xanthine oxidase activity by high performance liquid chromatography with electrochemical detection]. AB - A non-radiochemically sensitive method for the determination of xanthine oxidase (XO, EC 1.1. 3.22) activity is devised. We have enabled to detect the low activity of XO in human serum or peripheral lymphocyte lysates by the pretreatment of samples with activated charcoal, and by the employment of a sensitive high-performance liquid chromatography with electrochemical detection. This method was shown to be reliable and reproducible, and allowed us to evaluate XO activity in various clinical samples. XO activity in serum, but not in peripheral lymphocytes reflected the degree of liver damage. No relationship was found between serum XO activity and serum uric acid. No XO activity was detected in sera from patients with hereditary xanthinuria. These results suggested this method to be quite useful for rapid diagnosis of the patients with abnormal purine metabolism, especially in that with hereditary xanthinuria. PMID- 1307616 TI - [Study of prognostic factors and estimation of prognosis in patients with fungemia]. AB - INTRODUCTION: The estimation of prognosis is necessary in the treatment of fungemia because of its high mortality rate. We studied prognostic factors and estimated prognosis by scoring clinical and laboratory findings in 41 patients with fungemia treated at Tenri Hospital between 1976 and 1990. RESULTS: Although the mortality rate was low (33%) in 18 patients in whom the route of infection had been an intravenous catheter or the urinary tract, it was high (91%) in 23 patients with other or unknown route of infection. The risk of death was high in patients with disseminated intravascular coagulopathy (DIC), shock (systolic blood pressure > or = 90 mmHg), malnutrition (cholinesterase < 0.05 delta pH and albumin < or = 3.0 g/dl), renal failure (urea-N > or = 30 mg/dl and creatinine > or = 3.0 mg/dl), neutropenia (neutrophils < or = 500/microliters) or advanced age (age > or = 60 years old). Application scoring system taking into account of the presence or absence of DIC or shock, the degree of malnutrition, renal failure and neutropenia, and age (20 possible points) in 36 patients revealed that the scores of the 23 patients who died significantly different from those of the 13 survivors; score was less than 6 in every survivor (100%), while it was more than 6 in twenty-two (96%) of the patients who died. Seven of 10 patients with persistent fungal infection had greater than 15. CONCLUSION: The prognosis of patients with fungemia is adversely influenced by the presence of DIC, shock, malnutrition, renal failure, neutropenia and advanced age, and the scoring of these clinical and laboratory findings is useful in the estimation of prognosis and detection of persistent fungal infection in these patients. PMID- 1307617 TI - [Historical aspects of clinical enzymology]. AB - The field of clinical enzymology has markedly progressed in recent years. Diagnostic enzymology, therapeutic enzymology and enzymes as analytical reagents continue to contribute to the progress of health care. However, there are many aspects of the historical changes that have taken place in this field that are surprisingly unknown. The presentation I am about to give attempts to provide an overview of the history of the development of clinical enzymology and clinical chemistry. I hope it will be of reference to you. PMID- 1307618 TI - [Symposium: the role of laboratory medicine in modern medical care--chairman's remarks]. AB - Recent developments in laboratory techniques have brought dramatic changes in medical diagnosis, that is, a change from physical diagnosis to laboratory diagnosis. It is imperative that laboratory medicine develop further to meet the continuously growing needs of medical care. Major progress in medical care is classified into two categories, (A) treatment of severe disorders by modern technology and (B) health maintenance to prevent disease and achieve a higher quality of life. In this symposium, category (A) is subdivided in to (A-1) development of new drugs and (A-2) organ transplantation. In (A-1) the field of new drugs, "Recent Trends in Granulocyte Colony Stimulating Factor Therapy and its Relation to Clinical Laboratory Tests" is reviewed as an example of applying recombinant peptides to treatment. In (A-2) transplantation, two papers (A-2a) "Effect of HLA Matching in Renal Transplantation" and (A-2b) "Liver Transplantation and Function of the Graft Liver" are reported. In category (B), health maintenance, (B-1) exercise and (B-2) nutrition are important subjects. (B 1a) "The Role of Clinical Laboratory Examinations During Physical Exercise Therapy for Diabetes Mellitus" and (B-1b) "Exercise Loading Test for Evaluating Cardio-Pulmonary Functions" are given attention. In (B-2) nutrition, artificial feeding, such as intravenous hyperalimentation (IVH) is a current issue. The role of laboratory medicine in modern medical care will be discussed under each of these subjects. PMID- 1307619 TI - [Physical exercise therapy in diabetes mellitus--the role of clinical laboratory examinations]. AB - Physical training has been generally recommended for patients with diabetes mellitus as a basic therapeutic tool. In the present study the metabolic and endocrinological effects during the training program were examined in patients with non insulin dependent diabetes mellitus (NIDDM). Moreover the significance of continuous blood lactate monitoring and that of the determination of plasma atrial natriuretic polypeptide (ANP) during exercise loading in diabetics was also studied. (1) The glucose metabolic clearance rate (MCR) during euglycemic insulin clamp was higher in athletes than in patients with NIDDM and control subjects. (2) MCR increased significantly in the training group after the eight weeks program and a significant relationship between the changes of MCR and those of HbAIc observed. Moreover a decrease in the triglyceride level and increase in the HDL cholesterol level in plasma were significantly related with the improvement of MCR. (3) A continuous blood lactate monitoring system was newly developed. This system was simple and showed good reproducibility. The anaerobic threshold (AT) determined using this system corresponded to that obtained by respiratory gas analysis. It was useful for the determination of the exercise intensity without overloading in patients with diabetes mellitus. (4) The increase of plasma ANP during exercise loading was higher in diabetics than healthy controls, and a significant relationship was found between the increment of ANP during exercise and the diastolic function judged from the echocardiogram in diabetics. In conclusion clinical laboratory examinations and medical checkups are important in the practice of physical exercise therapy in patients with diabetes mellitus. PMID- 1307620 TI - [Liver transplantation and functions of the graft liver]. AB - Partial liver transplantation from living donors is a new surgical operation on patients in the final stage of liver dysfunction. Among about 90 operations so far done in the world, 34 were performed at the Second Department of Surgery in Kyoto University Hospital (as of June, 1992). Good but limited cooperation between surgeons and clinical laboratories has contributed to saving the lives of as many as 28 patients. Analysis of laboratory data and clinical course of patients indicated that pre-, mid-, and postoperational examinations of blood flow through the graft liver by the use of Doppler echography and the monitoring of the liver capacity to generate ATP by the aid of the arterial ketone body ratio are most important for early detection of dysfunctioning liver grafts. An unusually high incidence of the transient hyperphosphatasemia-like elevation of alkaline phosphatase and a frequent appearance of liver-type arginase in serum during the postoperative stage seemed to indicate some pathological changes of the liver. PMID- 1307621 TI - [Effect of HLA matching in renal transplantation]. AB - Evaluation of HLA-matching is useful in determining graft function and survival in a recipient in cadaveric renal transplantation. The effects of HLA on graft function, which serum creatinine indicative of, and graft survival were examined in both living and cadaveric transplantation in 280 Japanese renal transplants performed at Osaka University and Osaka Prefectural Hospital between October, 1982 and December, 1991 (cadaver 68, living 212). HLA-DR mismatch had a strong effect in living transplants, whereas no disparity was found in cadaver transplants with HLA-DR mismatch. HLA-B, DR mismatch had more effect than HLA-DR in cadaver transplants, and the same effect as HLA-DR in living transplants. HLA AB affected graft function. It can be used to predict the effect of long-term graft survival. The HLA-haplotype match had the strongest association with graft survival and function in both cases of living and cadaver transplants. HLA haplotypes of a cadaveric donor and a recipient were presumed by means of the linkage disequilibrium. These findings showed that HLA-matching, especially of haplotype, is an essential factor in relatively low risk renal transplant survival and function. 1-haplotype-matched transplantation, determined by the family study or presumed by the linkage disequilibrium is recommended if not 2 haplotype matched. PMID- 1307622 TI - [Reevaluation of optimum extraction condition for urinary organic acids using a stable isotope dilution technique]. AB - We reevaluated the optimum conditions for analysis of 13 urinary organic acids using solvent extraction and GC/MS by the stable isotope dilution technique. The acids analyzed were uracil, and lactic, oxalic, 3-hydroxybutyric, succinic, fumaric, glutaric, adipic, pyroglutamic, 2-ketoglutaric, orotic, sebacic, and citric acids. Analytical recovery and accuracy for 13 organic acids ranged from 90 to 107% and from 1.6 to 13.7%, respectively. The optimal pH for most organic acids was 1-2, while that for oxalic and citric acids was 0.25, and that for 2 ketoglutaric and orotic acids was 0.5. The presence of urinary albumin decreased the extraction rates of organic acids, especially of orotic and citric acids; in slight albuminuria (0.5 g/l) the extraction recovery (the extraction rate with albumin/that without albumin) of orotic and citric acid was 38% and 67%, respectively, and in more marked albuminuria (5 g/l), 6% and 26%. Membrane pretreatment with Centricon-3 improved these extraction rates under the condition of albuminuria. Dehydration with the desiccant agent decreased urinary acid extraction rates, especially of uracil and orotic and citric acids. The extraction rates of these three organic acids was decreased in albuminuria and by the desiccant agent. Accurate quantitative analysis of urinary organic acids by the stable isotope dilution technique is necessary for routine examination conducted in clinical laboratories. PMID- 1307623 TI - [Determination and clinical significance of human hepatocyte growth factor in serum]. AB - Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. In the present study, we evaluated an enzyme-linked immunosorbent assay, using monoclonal antihuman HGF (h-HGF) antibody, for measuring serum h-HGF levels. Intra- and inter-assay coefficients of variation were 2.2-3.3% and 3.4-4.0%, respectively. Detection limit of this method was 0.1 ng/ml, determining by the dilution test. The substances tested did not interfere with this assay, except for high concentrations of hemoglobin. Furthermore, no interference was observed with plasminogen and lipoprotein (a), which show the structural homology to h HGF, and with various kinds of cytokines. Reference ranges of serum h-HGF determined with 187 healthy subjects were 0.1-0.23 ng/ml. Serum h-HGF concentrations were increased in various kinds of liver diseases, in particular those were significantly higher in fulminant hepatic failure. Furthermore, prognosis of the patients with higher h-HGF values were strikingly worse than those with lower levels. We concluded that the determination of serum h-HGF plays important roles in the early diagnosis and prognosis of fulminant hepatic failure. PMID- 1307624 TI - [Cytofluorometric analysis of DNA content in proliferating cells of coronary arteriosclerotic lesions]. AB - Cytofluorometric determination of DNA content was done on paraffin-embedded tissues of 19 cases of coronary arteriosclerotic lesions including fibrocellular intimal thickening lesions (FT) or atherosclerosis (AS). DNA distribution pattern of medial smooth muscle cells of coronary arteries with FT and AS was all diploid. The average proliferative index (PI) of both medial smooth muscle cells of coronary arteries with FT and AS was 4.8 +/- 0.6. DNA distribution patterns of intimal cells of coronary arteries with FT and AS were also diploid. The average PI of intimal cells of coronary arteries with FT and AS was 8.4 +/- 1.0 and 9.1 +/- 0.7, respectively. These results suggest that intimal cellular proliferation plays an important role in the development of atherosclerosis. PMID- 1307626 TI - [Detection of Campylobacter species by using polymerase chain reaction and nonradioactive DNA probes. II. PCR direct sequencing of the Campylobacter DNA]. AB - We have developed a sensitive DNA hybridization assay for the detection and identification of Campylobacter species which are recognized as important pathogens of acute diarrheal disease in humans. This technique utilizes DNA probes complementary to nucleotide sequences present in 16S ribosomal RNA (rRNA) of C. jejuni, C. coli, C. laridis, C. fetus, C. fetus subsp. fetus, C. fetus subsp. venerealis and C. hyointestinalis, and polymerase chain reaction. The partial sequence of DNAs encoding the Campylobacter rRNA was first analyzed by direct solid phase sequencing in order to select suitable DNA probes. Amplified target DNA of 240 base pairs could be resolved on ethidium bromide-stained gels, and hybridized with DNA probes conjugated to alkaline phosphatase. In identification experiments, one of the 10 probes tested here gave a positive hybridization reaction with C. jejuni, C. coli and C. hyointestinalis but not with other Campylobacter species. The other was specifically reactive with C. fetus, C. fetus subsp. fetus and C. fetus subsp. venerealis. When applied to stool specimens, a good correlation was found between the results obtained by the present assay and by biochemical tests. These findings suggest that the nonradioactive probe assay can be used as the practical criterion for differentiating Campylobacter species. PMID- 1307625 TI - [Immunohistochemical study of the lymph-follicles and lymphocytes in the gastric mucosa]. AB - Immunohistochemical stainings according to ABC method (UCHL-1,L-26,MT-1,MB 1,IgG,IgA,IgD,IgM, kappa, lambda, LN-1 and LN-2) for the lymphocytes in the germinal center, mantle zone and infiltrative lymphocytes in the gastric mucosa of 30 cases of chronic gastritis and 10 cases of reactive lymphoreticular hyperplasia (RLH) were performed. Lymphocytes in the germinal center and mantle zone consisted usually of B-cells positively stained by L-26 and MB-1. However, in the interstitially infiltrative cells,T-cells positively stained by UCHL-1 and MT-1 were not infrequently contained. Immunoglobulin stainings revealed marked positivity for IgG,IgA,IgD,IgM, kappa and lambda in the interstitial lymphocytes and plasma cells. As to the RLH, small number of T-cells scattered in the germinal center and surrounding area of lymph follicles, and large number of T cells were found among the follicles, where B-cells were more infrequently found than in the interstitial area of propria mucosae. Confusion of enlarged germinal centers and monotonous proliferation of lymphocytes among the lymph follicles showing monotonous positivity for the stains of heavy and light chains in the cases of RLH were suggestive of malignant change. PMID- 1307627 TI - [Identification and differentiation of the human herpes virus group using the PCR method]. AB - Six kinds of human herpes viruses have been identified and classified on the basis of structure and characteristics. We studied the identification and classification of these types using PCR to amplify the virus-specific DNA sequences. This method showed higher sensitivity than the conventional method of virus isolation and culture for HSV and CMV detection. For each positive control, the viral DNA was amplified only when the complementary primers themselves were used. PCR apparently detects only the activated virus, because normal controls were negative when this method was used. Therefore, the present method is thought to closely reflect viral activation and infectious diseases in patients with latent infections. PMID- 1307628 TI - [Comparable evaluation of serological diagnostic tests (ELISA, IFA and PA methods) for the detection of anti-Borrelia burgdorferi antibody]. AB - We have evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA) and particle agglutination (PA) method as serological screening tests for Lyme-borreliosis. Serum samples obtained from two patients with Lyme-borreliosis showed marked high antibody titers for Borrelia burgdorferi when measured by these methods. Of the serum of 368 healthy members of the Self-Defense Force in north-eastern Japan screened for the antibody to B. burgdorferi, 8.4%, 3.7%, 4.6% were found positive by the ELISA, IFA, and PA method, respectively. However, Western blot analysis of these "positive" sera demonstrated no identical bands to those seen in the serum from the patients with Lyme-borreliosis. While 85% and 15% of Treponema pallidum hemagglutination test (TPHA)-positive sera (20 samples) showed a false-positive reaction by the ELISA and IFA method, respectively, no cross-reaction to the anti B. burgdorferi antibody was observed in these sera by the PA method. The analysis of the serum of the patients with autoimmune diseases (rheumatoid arthritis; 11 cases, systemic lupus erythematosus; 46 cases) by the ELISA and PA methods resulted in a cross-reaction to some extent, which suggested that the antibodies produced by autoimmune mechanisms such as the anticardiolipin antibody can cause a cross-reaction to the anti-B. burgdorferi antibody. These findings indicate that the PA and ELISA rather than the IFA method should be recommended for rapid and conventional screening of Lyme-borreliosis and that serum "positive" for the anti-B. burgdorferi antibody determined by these tests should be confirmed by Western blot analysis to negate the cross-reactions. PMID- 1307629 TI - [False positive reaction in measurement of allergen-specific IgE--comparison of 3M IgE FAST-Plus Test using polystyrene well as adsorbent with Phadezym RAST]. AB - Irrelevant IgE binding to cellulose discs is known to give false positive results in Phadezym RAST (Pharmacia) for the estimation of allergen-specific IgE in serum. We investigated FAST-Plus Test (3M Diagnostic Systems), an enzyme-linked sandwich type Fluoro-Allergo-Sorbent Test in which a particular allergen was coated to polystyrene well. Phadezym RAST and CAP RAST (Pharmacia) using cellulose-derivative discs as adsorbent were used as reference methods. Patients' sera which gave negative blank reactions to uncoated filter paper disc in the Phadezym RAST system were assayed for specific IgE to 6 allergens using FAST-Plus Test, CAP RAST and Phadezym RAST, and the results of the former two were compared with those of Phadezym RAST using a comparable class system. FAST-Plus Test showed variable correlations with Phadezym RAST, the correlation coefficients ranged from 0.41 to 0.97 (r = 0.462 in house dust 1, r = 0.713 in house dust 2, r = 0.412 in Candida albicans, r = 0.952 in Dermatophagoides peteronyssinus, r = 0.969 in Dermatophagoides farinae and r = 0.682 in Japanese cedar), although most of the results were within one class difference. Similar correlations were obtained between CAP RAST and Phadezym RAST. Of 3004 patients' sera tested in the past two years using Phadezym RAST, 132 (96 cases) displayed positive blank reactions to the uncoated filter paper disc. Of the 96 cases, 80 sera were assayed for binding of IgE to the uncoated cellulose-derivative disc in the CAP RAST system. 18 showed positive results up to 7 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307630 TI - [Recent advances in laboratory tests for liver diseases]. AB - Many tests for hepatitis C virus (HCV) infection have been developed and have proved useful for prevention of post-blood transfusion hepatitis C. However, there are at least 4 genotypes of HCV and the predominant type is different among countries. None of the tests using antigens from one genotype are sensitive in detecting the antibodies against another genotype. More sensitive tests using a more stable part of the HCV RNA sequences such as 5'-noncoding region must be developed for clinical use. Automated PCR methods and DNA sandwich hybridization methods using branched DNA amplification multimers may be candidates. Recently a hepatocyte growth factor test has been developed in Japan. Multicenter trials of this test reveal that it is useful for assessment of acute severe hepatitis. Tests for collagen type IV, fibronectin receptor, and prolyl hydroxylase have been reported useful for assessment of liver fibrosis. However, serum prolyl hydroxylase is prone to increase in response to hepatocellular damage as well as fibrotic processes. Enzymatic methods for determination of branched amino acids and tyrosine have been developed. The molar ratio of branched amino acids to tyrosine seems to have same pathophysiological meaning as the ratio of branched amino acids to aromatic amino acids (Fischer ratio) in assessment of liver cirrhosis. Lidocaine test is reported to be useful for predicting survival of transplanted liver and also assessing the function of the cirrhotic liver. Profiles of alpha-fetoprotein subfractions based on lectin-reactivity and galactosyl transferase II isoenzyme have been reported to be useful for detecting hepatocellular carcinoma but this remains to be proved. PMID- 1307631 TI - [Blood coagulation factors in hepatic disorders]. AB - The major factors related to the coagulo-fibrinolytic reactions are synthesized in the hepatic cells. As a reticuloendothelial organ, the liver also removes the activated factors and metabolic products in the coagulo-fibrinolytic process from the plasma. Therefore, many investigators have been trying to use measurements of the coagulo-fibrinolytic factors for the evaluation of the type and degree of a hepatic disorder and for the determination of therapeutic effects or prognosis. On the other hand, the recent advances in the blood coagulation study show that the hemostatic mechanism is a kind of maintenance mechanism of homeostasis for blood-flow. The functions of many factors in and from the platelets and vascular endothelial cells as well as those produced by the liver have been identified. Recently, some hemostatic molecular markers and complexes of activated factors with their inhibitors can also be measured. In this article, the recent concept of hemostatic mechanism and the relation between various hemostatic factors and hepatic disorders are presented. PMID- 1307632 TI - [Effects of antibiotics on the dissociation of platelet adherence in pseudothrombocytopenia]. AB - To elucidate the effects of antibiotics on platelet adherence phenomena, we examined dissociation of platelet adherence in EDTA-dependent pseudothrombocytopenia by adding Kanamycin or Colimycin. We found the rapid dissociation of platelet adherence caused by addition of Kanamycin (20 mg) or Colimycin (20 mg) in 1 ml of EDTA-anticoagulated blood from patients with EDTA dependent pseudothrombocytopenia. This dissociation was most remarkable in the sample treated within 30 minutes after venipuncture. When the dissociation occurred, no adherent platelet was found on microscopical examinations. Complete blood cell counts and their histogram patterns after dissociation were almost same as those just after venipuncture. The dissociation occurred as soon as the antibiotics were added and remained fairly long time. The dissociation decreased in proportion to the periods of time between venipuncture and addition of antibiotics. The dissociation was caused by many other antibiotics. However, severer damage were found morphologically by adding most of them in both histogram patterns and microscopical examinations than those of aminoglycoside or peptide antibiotics. PMID- 1307633 TI - [Evaluation of novel assays for the detection of crosslinked fibrin degradation products in whole blood by the agglutination of the red blood cells]. AB - We evaluated the clinical significance of two novel assays for the detection of crosslinked fibrin degradation products (XDP) in whole blood using the agglutination of the red blood cells (SimpliRED D dimer and SimpliRED D dimer 500, AGEN, Australia). XDP made serially by plasmin in vitro, were detected by the SimpliRED D dimer assay, but fibrinogen degradation products showed weak reactivity. Ten of the fifty four clinical samples collected with EDTA-2K, changed to positive on these assays after overnight incubation at 4 degrees C. Anemia and hemolytic samples had no effect on the assay results. The results obtained by the SimpliRED D dimer were negative for the normal subjects (n = 50) without exception. In our study, 81% and 95% of the patients, who showed abnormal levels of XDP in plasma and E fragments in serum respectively, were positive on the SimpliRED D dimer assay. The assay was as sensitive as the Rapidia-D dimer assay. In conclusion, the SimpliRED D dimer assay was clinically useful as a screening assay for the diagnosis of hypercoagulable and fibrinolytic states, since it could be performed simply and quickly. PMID- 1307634 TI - [Changes of differential leukocyte counts during pregnancy and in the postpartum period]. AB - We examined differential leukocyte counts in peripheral blood from 177 pregnant and postpartum women with an automated leukocyte differential system, and compared them with those of 52 nonpregnant and non-postpartum women. The proportions and numbers of neutrophils and monocytes increased throughout pregnancy, returned to the non-pregnant levels within one month after delivery, and decreased transiently at 4 or 7 to 10 months postpartum. The proportions and numbers of lymphocytes and eosinophils decreased throughout pregnancy, and increased transiently at 4 to 10 months postpartum and one month postpartum, respectively. The proportion and number of basophils decreased during pregnancy and one month postpartum, and those of large unstained cells (LUC) decreased in the third trimester of pregnancy, and both returned to the non-pregnant levels at 4 months postpartum and within one month postpartum, respectively. These data indicate that differential leukocyte counts change dynamically during pregnancy and after delivery until 1 year postpartum. PMID- 1307635 TI - [Clinical usefulness of benzoate tolerance test in patients with liver cirrhosis]. AB - The capacity of the liver to metabolize intravenously loaded benzoic acid to hippuric acid was examined in 7 healthy adults and 18 patients with liver cirrhosis. Blood samples were withdrawn at 5 to 120 min after infusion of benzoic acid (15 mg/Kg), and then serum was obtained to determine the contents of the fatty acids by HPLC as well as to examine several pharmacokinetic parameters under a two-compartment model program. The urinary samples were collected at 60 min after the infusion. In the serum of the patient group, the maximum concentration (Cmax) and area under the concentration curve from zero time to the infinity (AUC) for benzoic acid remained in the normal range, but the mean transit time(MRT) and half-life time(T1/2) were significantly delayed. In serum of the patient group, the AUC for hippuric acid was hardly reduced but the Cmax was significantly reduced. Moreover, MRT, T1/2 and time to reach Cmax(Tmax) were significantly delayed. In urine at 60 min after the loading, benzoic acid was below the limit of detection and was recovered as hippuric acid with a recovery rate of 70% in the healthy adult group and 40% in the patient group. PMID- 1307636 TI - [Clinical and laboratory correspondence to outpatients with the extreme value of C-reactive protein]. AB - INTRODUCTION: It is the policy of Tenri Hospital to notify the patient promptly whenever an extreme laboratory data value is detected. We investigated the utility of forwarding clinical and laboratory correspondence to outpatients with extreme value of C-reactive protein (CRP). MATERIAL AND METHOD: Sixty-eight outpatients with CRP levels more than 20 mg/dl detected during 1986 were studied. CRP was measured by turbidometric method, and a sample with CRP level more than 15 mg/dl was diluted with CRP negative serum (CRP level less than 0.2 mg/dl) and was reanalyzed. RESULTS: Fifty-two of 68 patients (76%) had infectious diseases as the causal disease of high CRP, and eight (12%) had other diseases. In the remaining (12%) the causes were unknown. In most patients the causal diseases were diagnosed within one or two days, but diagnosis required more than 4 days in those with acute pyelonephritis, meningitis, liver abscess or renal abscess, as these diseases were diagnosed after the examination of urine or cerebrospinal fluid, or after ultrasonography. Thirty-seven of 58 patients (64%) who had appointments with their physician on the day of the laboratory examination were admitted the same day, and two of 10 patients (20%) who had appointments on the following day were admitted on that day. Seventeen of 25 patients (68%) with urea N levels more than 30 mg/dl, cholinesterase levels less than 0.7 delta pH and albumin levels less than 3.5 g/dl required more than 15 days to recover, while 29 of 32 patients (91%) with only 2 or fewer of these laboratory values required less than 14 days. CONCLUSION: The prompt notification of extreme CRP value is an important aspect of medical care. The examination of urine and cerebrospinal fluid and ultrasonography are necessary screening techniques accompanying examination of blood and plain chest X-ray. Urea-N, cholinesterase and albumin values should be determined at the same time as CRP value to assess prognosis. PMID- 1307637 TI - [O-serotypes, biotypes, and antimicrobial susceptibility of Serratia marcescens isolates from clinical specimens: 3rd report]. AB - O-serotypes, biotypes, and drug resistance of Serratia marcescens strains isolated from various clinical specimens in Showa University Fujigaoka Hospital were investigated: period I (1979. 1-1982.3), 122 strains; period II (1983. 1 1985. 3), 198; period III (1985. 4-198. 3), 129; period IV (1989. 1-1991. 3), 99. The frequency of serotype O 3 was higher than those of the other serotypes after the period II and ranged 17 to 37%. The isolation frequency (27%) of serotype O 4 was higher than those of other serotypes in the period I. However, this frequency decreased in the period II to III and, in the period IV (10%), was higher than in the period III. The isolation frequency of serotype O 17 suddenly increased in the period II (27%) alone, and 42% of the biotypes, obtained with API 20E, showed 5305701. The isolation frequency of non-typable strains ranged 9 to 14% through all periods. The group including 5317721 and 5307721 clustered by the furthest neighbor method, more frequently appeared through all periods. The former code of urease positive more frequently appeared in the period II to IV. The isolation frequency of the latter code of urease negative reduced to a minimum (18%) in period II, though it increased in the period II to IV. The isolation frequency (22%) of the pigmented strains in the period IV increased much higher than in the period I to III (ranged 2 to 4%). The frequency of the pigmented strains of serotype O 3, not belonged to the Grimont's biotype, was 27% of all pigmented strains isolated in the period IV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307638 TI - [A study of intraoperative rapid frozen section diagnosis focusing on accuracy and quality assessment]. AB - Accuracy of frozen section (FS) diagnoses was investigated in a consecutive series of 1129 intraoperative consultations. In our series, the correct diagnosis including clinically not serious minor errors was made in 96.9% of the cases. Whereas the accuracy ratio of FS diagnosis for unknown pathologic process decreased to 92.2%. Among all the types of tissues, central nervous system was shown to be the most frequently handled for FS, followed by lung/bronchus, breast, liver/biliary tract, lymph node and so forth. The requesting ratio of FS, on the other hand, tended to be high in the following specialties; neurosurgery (46.5%), thoracic surgery (19.0%), general surgery, (10.0%). Deferred diagnosis with a provisional diagnosis and misinterpretations in histology typing without serious clinical problem accounted for 2.7% and 3.1% respectively. Causes of erroneous diagnoses seemed to be multifactorial, such as inappropriate sampling, diagnosis on poor quality histology sections, lack of clinical information, lack of enough experience in FS practice of pathologists, or a combination of more than two of them, though inevitable cases showing minimal cytological and structural atypia were included. Intraoperative consultation by FS diagnosis is now essential to serve a good quality medication to patients. It is thus necessary that to establish a tight peer review system and also to provide an education program with regard to practice in FS diagnosis particularly for young pathologists. PMID- 1307639 TI - Non-ulcer dyspepsia. AB - During the last decade a new disease entity numbered among functional disorders of the digestive tract and defined as "non-ulcer dyspepsia", has been isolated. This disease is diagnosed most frequently at the age of 20 to 40 years. In West European countries it is diagnosed in about 30% of out patients. Symptomatology of the disease is very ample and is, after exclusion of organic diseases of the digestive tract, the basis of diagnosis and classification. Present knowledge on the pathophysiology of "non-ulcer dyspepsia" is incomplete and based mainly on study results of the motility of the stomach and small intestine under manometric examination. In spite of that one attains satisfactory therapeutical effects during a prolonged administration of prokinetic drugs (dopamine receptor antagonists and peripheral parasympathomimetics). PMID- 1307640 TI - Role of oxygen radicals in hepatocellular impairment in cerulein-induced acute pancreatitis. AB - Acute pancreatitis was induced in male Wistar rats by i.v. infusion of cerulein in the dose of 5 x 10(-6) g x kg-1 x h-1 for periods of 3 and 12h. The most important finding in our study was the increase of malondialdehyde concentration in hepatic tissue, observed after 12 h of cerulein infusion, accompanied by ultrastructural changes predominantly in the sinusoids. Obtained date suggest that products originating from lipid peroxidation in pancreatic tissue, in concert with activated Kupffer cells, may be responsible for such impairment of hepatic tissue. PMID- 1307641 TI - The effect of coffee deprived of irritant substances upon some indices of lipid metabolism in healthy volunteers and patients with hyperlipoproteinemia. AB - Effect of 14 days coffee drinking upon some blood serum indices of lipid metabolism was studied on 20 healthy volunteers and 20 patients with hyperlipoproteinemia (type IIb). The study was done in two subgroups: healthy volunteers or patients with hyperlipoproteinemia which had belonged to the first subgroup drank ordinary coffee and the ones which belonged to the second subgroup drank coffee deprived of irritant substances. (4 glasses per day). It was found that in healthy volunteers ordinary coffee had given rise to a significant increase of serum total cholesterol and to a decrease of serum HDL-cholesterol. These changes were not observed in subgroup drinking coffee deprived of irritant substances. More significant rise of serum total cholesterol and decrease of serum HDL-cholesterol were found in patients with hyperlipoproteinemia. Drinking of modified coffee does not cause any significant changes in serum indices of lipid metabolism. The authors concluded that drinking of ordinary coffee should be restricted in patients with hyperlipoproteinemia and coffee deprived of irritant substances might be recommended to patients with this disease. PMID- 1307642 TI - Esophageal motility in the personnel operating heavy self-propelled mining machines. AB - We examined 47 men exposed to whole-body vibration for a long time (average 9.8 years) and tested esophageal motility. The following parameters were measured: mean pressure in the body of esophagus during the passing of peristaltic wave, maximum value of pressure during the passing of peristaltic wave, mean and maximum duration of spasm and peristaltic wave transmission velocity was calculated. In over 1/4 exposed to whole-body vibration disorders of esophagus motility were observed. These disorders are probably a consequence of vocational exposure to whole-body vibration. PMID- 1307643 TI - Assessment of clinical value of Bernstein test and attempts of its modification. AB - Bernstein test has been applied for over 30 years in the diagnosis of the causes of pyrosis. Its drawback is a considerable percentage of false positive results in healthy persons, caused by a too large amount of 0.1 M HCl given. Presented in the paper are studied results in 34 patients with symptoms of gastroesophageal reflux disease (GERD), and in 23 healthy persons in which into the body of the esophagus and into the cardia was given alternately 0.1 M HCl and 0.15 M NaCl at a speed of 0.8 cm3.min-1. During the testing the complaints reported by the patients were recorded, and by means of polyphysiograph the spasms of the body of the esophagus were recorded and morphologically assessed. In addition, in 12 volunteers of 23 healthy persons Bernstein classic test was carried out by giving them alternately 0.1 M HCl and 0.15 M NaCl at a speed of 0.8 cm3 x min-1. The testing carried out shows that a reduction in the amount of acid given in Bernstein test causes a decrease in the percentage of false positive results in healthy persons. HCl infusion into the body of the esophagus and into the cardia in patients with symptoms of GERD caused pathological motility in the body of the esophagus. The most frequent anomaly were multipeaked spasms, which can be an additional diagnostic criterion of this disease. PMID- 1307645 TI - Surgical reconstruction of the oesophagus. AB - Reconstructive oesophageal surgery underwent 322 patients in our clinic. The surgery was indicated because of cicatrical obstructions or cancer of the thoracic part of the oesophagus. The continuity of the alimentary tract was re established by pedunculated intestinal segment from the jejunum, ileum or left side of the colon in the anisoperistaltic position. The right side of colon was used either in iso- or anisoperistaltic position. The follow-up after completion of the reconstructive operation ranges from 1-40 years. PMID- 1307644 TI - Disturbances of the pulmonary perfusion after endoscopic sclerotherapy of oesophageal varices. AB - Haemorrhage from oesophageal varices is one of the most common reason of death of patients with liver cirrhosis. The possibility of treatment and prevention of the haemorrhage by endoscopic sclerotherapy (ES) has become one of the achievements of contemporary medicine. Nevertheless there are some complications described after this procedure, the most severe being the pulmonary embolia. In our study we analyzed the pulmonary circulation by perfusion scintigraphy after ES. Among twelve patients treated by ES we found two cases of disturbed pulmonary perfusion. We did not find clinical or gasometric changes in these patients. We suggest there should be done pulmonary perfusion monitoring after ES. PMID- 1307646 TI - Helicobacter pylori, chronic gastritis and peptic ulcer. AB - H. pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Acquisition of the infection will lead to gastritis and the eradication of the bacterium results in healing and final cure of the gastritis. Chronic gastritis and H. pylori infection may occur in antrum and/or corpus, and will gradually result in atrophy of the underlying mucosa in a great number of affected persons. Correspondingly, impairments in several important functions of the gastric mucosa are consequences of the atrophy and inflammation. Hp infection and gastritis associate with important gastroduodenal diseases, such as peptic ulcer diseases and gastric cancer. There are reasons to suggest that the infection and subsequent gastritis precede these diseases, and that they are important risk factors for both disorders. In fact, peptic ulcer can be seen a late frequent complication of an H. pylori infection. In addition, the type and grade of gastritis can be used in prediction of the ulcer risk if adequate biopsy specimens are available for microscopy from both antrum and corpus mucosa (Table II). An association between chronic gastritis and Helicobacter pylori (Hp) infection is strong. Clearly more than 80% of cases with chronic gastritis are related to coexistent Hp infection. Furthermore, both Hp and gastritis are extremely common in patients with peptic ulcer supporting the view that they are causally related to the ulcer disease. Correspondingly, similar suggestions may also be presented about the links between Hp and gastritis in the pathogenesis of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307647 TI - Is the low anterior resection justified in midrectal cancer? AB - The main reasons for using a resection in midrectal cancer are presented. The knowledge about the direction of the lymph-drainage and the cell infiltration in the rectal wall and the progress in the dissection technique of the ampulla now allow the preservation of the sphincterorgan without severe oncological doubts. The results are well comparable with those after the exstripation but the comfort of the patient is better. PMID- 1307648 TI - The technique of the low anterior resection made by hand or with stapler. AB - After a short historical review of the surgical intervention for rectal cancer the precondition for the resection are presented. The technique of the resection is described in the following. We use routinely the double row suture for the anastomosis. Also the stapler technique for deeper localized growth is presented. PMID- 1307650 TI - Anal incontinence: evaluation and biofeedback therapy. AB - Incontinence is a very stigmatizing symptom in our society. About 1% of the adult population is affected by fecal incontinence. In the evaluation anorectal manometry and defecography play a major role. Therapy often is still disappointing. In recent years simple retaining or biofeedback therapy have been reported to improve about 70% of incontinent patients. Within one year we treated 19 patients. Success was achieved in 69%. Biofeedback training, therefore, should be attempted prior to considering surgery. PMID- 1307649 TI - Is steroid dependent Crohn's disease a separate entity? AB - Crohn's disease has been sometimes considered as a syndrome including different entities. In this prospect we tried to assess whether steroid dependent Crohn's disease could be a separate sub-group. Eighty five patients (mean follow-up: 6 years) with documented Crohn's disease were classified into 3 groups: 1--patients never treated with steroids (NS) (N = 37); 2--patients in whom steroids had been given but had been withdrawn (NSD) (N = 37); 3--patients dependent on continuous steroid therapy (SD) (N = 11). Ten variables were considered: age at onset, sex, CDAI, cumulative topography of lesions, extra-intestinal symptoms, albuminemia, ESR, surgical operations, annual frequency of relapses. Monofactorial analysis (analysis of variance and CHI2 test) showed group SD to be significantly different from group NS and in term of age at onset, CDAI, ESR, annual frequency of relapses, extra-intestinal symptoms, surgical operations. In contrast, a multivariate analysis of correspondences applied to the 3 groups and to 9 dichotomous variables showed that group SD is not a separate entity, but the limit of a continuum extending from group NS to group NSD. This was ascertained by a CHI2 test applied to the dichotomous variables. Thus, within the limits of this study Crohn's disease appears to be a homogeneous entity rather than a heterogeneous syndrome. PMID- 1307651 TI - Comparison of qualitative and quantitative blood determinations in stools of healthy persons and patients with colorectal tumours. AB - The possibility of using fecal blood determination for early diagnosis of colorectal cancer is based on the fact that in most cases bleeding from the tumour occurs early in the asymptomatic phase of the disease. The qualitative Haemoccult test is now regarded as most suitable for screening. The test is cheap and simple, but its drawback is a high per cent of false negative and false positive results. Therefore there is a need to look for other methods of greater sensitivity and specificity. One of these methods may be quantitative determination of blood in stools. The purpose of the present study is: 1) to assess the specificity of quantitative fecal blood determinations, 2) to compare the sensitivity of the qualitative and quantitative tests for the detection of colorectal neoplasms. Quantitative blood determination included the heating of stool samples with citric and oxalic acids. The citric acid reagent caused passing into the solution of the so called intestinal porphyrin fraction which is produced from haem spontaneously in the upper gastrointestinal tract. The oxalic acid reagent converts in vitro haem remaining in the stools to porphyrins, without changing the structure of the intestinal-fraction porphyrins. The obtained solutions were subjected to three-phase extraction for removal of non porphyrin substances. The concentration of porphyrins was read in a spectrofluorimeter at 402 nm excitation wavelength and 600 m emission wavelength. Haemoccult II test was used for qualitative blood determination in three consecutive stools. The result was considered as positive if the colour of the test slide was changed to blue within 30 seconds, at least in one of the six test "windows".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307652 TI - Diagnostic and surgical procedures in acute necrotizing pancreatitis (ANP). AB - The main subject of considerations is acute necrotizing pancreatitis, based on the authors opinion and literature. Frequency of the necrosis in acute pancreatitis is established in between 7-15%. Because of very severe and often lethal complications these patients need special surgical attention. Enhanced CT is the most valuable diagnostic procedure to visualize the extend of pancreatic necrosis. There is no common agreement upon the mode of treatment except from that infected necrotizing pancreatitis should be operated. Indications for surgical treatment with particular analysis to necrosectomy and laparostomy is discussed. PMID- 1307653 TI - The evaluation of clinical results of hepatic artery embolization. AB - The clinical symptoms and liver function following hepatic artery embolization (h.a.e.) in patients with inoperable liver neoplasms were evaluated. The study was performed on 28 patients 11 of whom were male in the age of 53-72 years and 17 female aged 16-76. Before embolization liver function was evaluated on the basis of clinical data and laboratory tests. Transcatheter hepatic artery embolization was performed using Spongostan. Following h.a.e. clinical status and biochemical analysis of blood and urine were checked repeatedly. Twenty-two patients developed post embolization syndrome dominated by: epigastric pain, nausea, and vomiting. Fourteen patients and disturbed intestinal motoric. All those symptoms were transient and lasted 1-3 days. Elevated body temperature was observed in 14 patients. There was a statistically significant increase of ALAT & AspAT after embolization lasting for a few days. There were however no statistically significant changes in the results of tymol test and total bilirubin level in blood. PMID- 1307654 TI - Effect of cisapride and cimetidine on 24-hour intraesophageal pH monitoring in patients with gastroesophageal reflux disease. AB - In 16 patients with symptomatic gastroesophageal reflux disease (GERD) 24-h intraesophageal pH monitoring (Medilog 1010, Oxford) was carried out after placebo, cisapride (4 x 5 mg) and cimetidine (3 x 200 mg plus 400 mg at bedtime). The per cent time at which intraesophageal pH < 4.0 (refluxive time) was analysed. Cisapride shortened daytime and postprandial refluxive time from 16.1 +/- 14.5% and 12.6 +/- 9.2% to 5.1 +/- 4.4% and 7.5 +/- 6.5%, respectively (p < 0.01, p < 0.05). Whereas, cimetidine shortened particularly night refluxive time from 24.7 +/- 14.1% to 8.8 +/- 6.9% (p < 0.01) and total time from 20.4 +/- 12.8% to 12.0 +/- 6.4% (p < 0.05). PMID- 1307655 TI - Low-dose antacids versus ranitidine in the short-term treatment of patients with duodenal ulcer. Endoscopic and histologic placebo-controlled study. AB - In this double-blind randomized placebo-controlled trial we compared the efficiency of two Polish antacids (Alugastrin, dihydroxyaluminium sodium carbonate and Alumag, aluminium hydroxide with magnesium hydroxide; buffering capacity 189 and 224 mmol) with ranitidine in the healing of duodenal ulcer. We also examined the effect of drugs on the frequency and severity of gastritis and selected morphometric parameters of the fundic mucosa. The study showed that low dose antacids effectively promote the healing of duodenal ulcer during four week therapy, similarly to ranitidine (72%, 76% and 80%, respectively) and significantly better than placebo (46%). Both antacids and ranitidine were without effects on the chronic gastritis and did not cause any trophic changes of the gastric mucosa. PMID- 1307656 TI - Primary health care nursing assessment and strategy for known hypertensive individuals working in metro Manila. PMID- 1307658 TI - Promoting wellness: nursing role. PMID- 1307657 TI - 70th foundation anniversary Philippine Nurses Association Manila Garden, October 21, 1992. PMID- 1307659 TI - Behavior modification in nursing practice (continuing education credit). PMID- 1307661 TI - [Development of a vestibulum section at the Department of otorhinolaryngology of the Russian medical university]. PMID- 1307660 TI - The role of the Philippine Nurses Association in health and development. PMID- 1307662 TI - [Creative legacy of academician B.S. Preobrazhensky and the traditions of clinico audiologic laboratory of the otorhinolaryngology department of the Russian medical university]. PMID- 1307663 TI - [Activity of the clinic at the time of B.S. Preobrazhensky 's arrest for the "Doctors' case"]. PMID- 1307664 TI - [Method for angiographic identification of the labyrinth artery]. AB - Digital subtraction angiography in Stenvers standard setting performed atraimatically has been tried in 106 emergency cases admitted to N. V. Sklifosovsky Research Institute of Critical Care. This new method of identification (in 75% of the cases) and verification of the labyrinthine artery intravitally proved safe and reliable. The patients were exposed to cerebral angiography by various methods for diagnosis of the underlying disease. Standard methods of vertebral angiography were found unsatisfactory. PMID- 1307665 TI - [Radiologic anatomy of the labyrinth artery]. AB - Carotid and vertebral angiographic investigations were performed to study x-ray anatomy of the artery of the labyrinth (AL) in 96 inpatients admitted to the N. F. Sklifosovsky emergency care clinic. According to the angiograms, AL originated from the distal parts of the inferior anterior cerebellar artery in 66.3% of the patients. In this case it has a straight form. When initiating from the proximal parts of the basilar artery (33.7% of the patients), AL was shorter (0.8 +/- 0.3 against 2.5 +/- 0.8 cm) and curved. In any case AL was situated along the upper edge of the pyramid before it entered the internal acoustic meatus. By the meatus or inside it AL forms a characteristic loop or semiloop. A complete AL left-right symmetry was observed in 61.8% of the cases. PMID- 1307666 TI - [Academician B.S. Preobrazhensky (1892-1970). Centenary]. PMID- 1307667 TI - [Characteristics of protein metabolism in labyrinthine tissue]. AB - The synthesis of total protein in organic culture of the internal ear was studied in 16-day embryo of CBA mice exposed to altering factors. The experiments showed feasibility of partial recovery for impaired metabolic processes in the labyrinth following phonophoretic introduction of mitochondrial coenzymes and inhibitors of lysosomal activity. Formation of systemic structural trace by modelling of acoustic stress and verification of protein stress agents was tested making it possible to identify an important component in dysadaption mechanism in mature CBA mice labyrinth. PMID- 1307668 TI - [The effectiveness of stabilographic vertebrogenic test in diagnosing secondary cochleovestibular disorders]. AB - The study included 211 healthy subjects, 65 and 95 patients with affected vestibular analyzer without hemodynamic disorders in the vertebrobasilar branches and with them, respectively. It was found possible to use the stabilographic vertebrogenic test (SVT) both for diagnosis of vestibular dysfunction in vertebrogenic insufficiency and prediction of its appearance. The range of SVT changes (12-17%) reflects subclinical level of vertebrogenic impact on equilibrium system induced by unfavorable effects on the peripheral or central structures of the vestibular analyzer. PMID- 1307669 TI - [Scientific legacy of academician B.S.Preobrazhensky]. PMID- 1307670 TI - [Pharmacological Society in Paris and its awards]. AB - The Societe de Pharmacie de Paris started in 1804 to award prizes firstly intended for students in pharmacy after competitive examinations, then, from 1807, for anyone devoted to the advancement of pharmaceutical sciences. Since 1861, the Societe de Pharmacie, which became Academie de Pharmacie in 1946 and Academie Nationale de Pharmacie in 1979, has payed particular attention to awarding a prize to the best thesis defended each year at the Ecole de Pharmacie de Paris (now Faculte de Pharmacie). PMID- 1307671 TI - [Current research on oxygen carriers for transfusion: hemoglobin solutions and fluorocarbon emulsions]. AB - Although products currently under study are usually called "artificial blood" or "blood substitutes", it concerns only, for the moment, to achieve preparations able to carry and release oxygen to tissues while allowing also a temporary restoration of "blood" volume. The most advanced scopes are related to hemoglobin solutions and fluorocarbons emulsions. The limitations of free hemoglobin impose to modify it. The reestablishment of a normal, even reduced, affinity for oxygen is obtained by the fixation on hemoglobin of a 2,3-DPG substitute whose most known example is pyridoxal phosphate. The enhancement of vascular retention may be achieved by intramolecular cross-linking, intermolecular polymerization or covalent binding of hemoglobin on macromolecules. The two modifications of hemoglobin must be performed successively et numerous possibilities have been proposed. Bovine and recombinant hemoglobins are also promising. Originally and logically, fluorocarbons are synthetic compounds derived from hydrocarbons by an important or maximal substitution of hydrogen by fluorine. The physical properties of these molecules, impose, for transfusion, their emulsification in an aqueous physiological solution. They need an oxygen enriched atmosphere and their storage in tissues is often extended. At present, the most known emulsion is Fluosol DA, a mixture of perfluorodecalin and perfluorotripropylamine. It allowed to realize numerous researches and the proposal of the multiple possible employment for this category of oxygen carriers. The limitations of Fluosol DA led to fluorocarbons under investigation such as F dimethyl bicyclononanes, F methyladamantane, bis (F-butyl) ethene or F-octylbromide. The new hemoglobin solutions and fluorocarbons emulsions start to meet the requirements of potential users. PMID- 1307672 TI - [Affinity chromatography for extracorporeal purification or for separation of molecules for biological use: technical and legal restraints]. AB - Affinity and/or immunoaffinity chromatography is one of the less commonly method used for large scale separation purposes. As this technic is greatly selective and gives high yields, it allows in vivo removal, in an extracorporeal circulation, of harmful substances in patient plasma as well as purification of molecules for biological and therapeutic uses. Large development with increased safety of such a method is dependent on some economic, technical and legal requirements. Particular attention must be drawn to the following points. Possibility of multiple uses of affinity supports contributes to lowering the cost of the method. Desorption agents should be chosen according to the best compromise between total desorption and preservation of adsorption capacity over runs. It is likewise essential to store affinity supports in conditions allowing prevention from contamination without loss of adsorption capacity. In developing and optimizing an affinity chromatography procedure, it is important to minimize the amount of ligand released from the affinity support. Besides economic and technical aspects, it is necessary to take into account legal requirements, particularly those related to the preparation of the ligand especially if it is monoclonal or polyclonal antibodies. An important consideration for the therapeutic use of antibodies (either in the preparation of biological products or in an extracorporeal circulation procedure) is the possible presence of viruses and/or potentially oncogenic macromolecules. Source material should be shown to be free of viruses, the cell banks (for monoclonal antibodies) and the production of antibodies must be closely controlled, viral inactivation of antibodies should be performed and the inactivation process should be shown to be effective. PMID- 1307673 TI - [Cerebral ischemia: massive increase of the dopamine release or stagnation?]. AB - Massive increase of the dopamine (DA) in the dialysates, obtained by cerebral microdialysis in the striatum or in the hippocampus, during cerebral ischemia in animals, was interpreted as a large increase of the DA release in these two cerebral areas. The experimental data analysis displayed in this paper suggests that it could rather be a stagnation of the DA and of the NA (in the hippocampus) as a result of the blood circulation arrest in these brain areas. Oxidation (chemical and enzymatic) of the accumulated DA and NA (in the hippocampus) could potentiate the action of the glumatergic receptors, responding to the N-methyl-D aspartic acid (NMDA), via their redox site and could originate, probably in association with other potentiating components (glycinergic or polyaminergic), the excessive neurotoxicity observed in the striatum or the hippocampus after cerebral ischemia. PMID- 1307674 TI - [Stabilization and function of liposomes]. AB - Liposomes stability can be improved by covering them with polysaccharide derivatives. The anchoring mechanism of these derivatives into the lipid membrane has been studied and explained. In order to improve liposome specificity, protein transfer from erythrocytes and platelets into liposome membrane has been carried out. The effect of a newly developed phospholipid, DDPC, on the efficiency and the selectivity of protein transfer is reported. PMID- 1307675 TI - [Structural typology assay of principal anticancer agents on the basis of molecular fragmentation]. AB - The developed formula of 58 anticancer agents used in therapeutic or still in clinical essays were treated by molecular connectivity matrix method. This technic allows the search and the automatically count of structural fragments of the different studied molecules. Then it has been possible to build a spanning tree (Prim's arborescent skeleton) which gathers the different molecules and permits to put a priori new structures. PMID- 1307676 TI - [Spasmolytic and antinoradrenergic activities of para-hydroxybenzonitrile on the isolated duodenum and vas deferens in rats]. AB - The para-hydroxy-benzonitrile (PHB) show spasmolytic activity of the muscular of duodenum provoked by acetylcholine or barium chloride. The results obtained on the vas deferent of the rat versus the contracture effects of norepinephrine show that PHB is an antagonist of the neuromediator on the post-synaptic alpha adrenoceptors. PMID- 1307677 TI - [Determination of silicon dioxide in colloidal silica]. AB - This is made without using hydrofluoric acid. The dissolution of silicas is carried out by ammonium fluoride in aqueous solution with potassium chloride. The potassium fluosilicate obtained is then isolated; its mass corresponds to 3,666 x SiO2. The values obtained corroborate the validity of this method. PMID- 1307679 TI - Left hemiparalexia. AB - Three patients with left splenial lesions made paralexic errors restricted to the left end of words. Errors appeared more frequently when a correct response was highly dependent on the initial letter of the stimulus. One patient had full visual fields with hemialexia affecting the left visual field. The other two patients had complete right hemianopia. We attribute left-sided reading errors in the hemianopic patients to a retinotopically restricted disconnection pattern that selectively disrupts transfer of information originating from the peripheral left visual field. Functional resistance of the more numerous transcallosal projections representing visual field adjacent to the vertical meridian may account for such a pattern. The emergence of positional reading errors from retinotopically restricted left hemifield disconnection suggests that callosal information transfer during normal reading may primarily involve elemental sensory rather than lexical/semantic information. PMID- 1307678 TI - Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model. AB - Little is known about delivery of aerosolised steroids to neonatal patients undergoing assisted positive pressure ventilation and after extubation. A rabbit model has been established to investigate factors influencing drug delivery. Beclomethasone dipropionate, in a metered dose inhaler, was radiolabelled with technetium 99m. The mass median aerodynamic diameter of the aerosol was 3.3 (2.0) microns and the impactor measurements confirmed that the technetium distribution corresponded with that of the drug particles. The metered dose inhaler was actuated into a collapsible spacer that was used to ventilate and deliver aerosol to anaesthetised rabbits by a tracheostomy. From each actuation of the drug 2.9 (0.4)% of the aerosol deposited in the trachea and main bronchi and 1.2 (0.4)% in the lung. When the drug was delivered by a spacer device, with face-mask attachment, to rabbits breathing freely through a tracheostomy, aerosol deposition increased to 4.4 (2.1)% in the trachea and main bronchi and 1.9 (0.9)% in the lung lobes. The maximum change in systolic blood pressure after administration of aerosol by the collapsible spacer was a decrease of 13%. The methods described may prove useful for the delivery of inhaled steroids to neonatal patients likely to develop bronchopulmonary dysplasia. PMID- 1307680 TI - Pneumocystis carinii pneumonia prophylaxis: past, present and future. PMID- 1307681 TI - Chronic cutaneous lupus erythematosus presenting as periorbital edema and erythema. AB - We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs. PMID- 1307682 TI - Penetrating trauma of the jugular foramen. PMID- 1307683 TI - JFK's death--the plain truth from the MDs who did the autopsy. PMID- 1307684 TI - Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. AB - A retrospective epidemiological study of ulcerative colitis (UC) and proctitis was performed in Leicestershire from 1972-89. Potential cases were identified from hospital departments of pathology, endoscopy, and medical records and from general practitioners. The county population includes more than 93,000 South Asians. There were 573 cases of UC and 286 of proctitis in Europeans and 115 cases of UC and 29 of proctitis in South Asians. The standardised incidence of UC in Europeans and South Asians was stable, except in Sikhs in whom it had increased rapidly. The relative risk of UC to South Asians was 2.45. The standardised incidences of UC in South Asians during the 1980s were: 10.8/10(5)/year in Hindus (95% confidence interval (CI) 7.4-14.1 cases/10(5)/year) 16.5/10(5)/year in Sikhs (95% CI 7.9-25.2 cases/10(5)/year), and 6.2/10(5)/year in Muslims (95% CI 1.6-10.9 cases/10(5)/year). There was no difference in incidence between Asians from East Africa and India. The standardised incidence of UC in Europeans was 5.3/10(5)/year (95% CI 4.3-6.3 cases/10(5)/year). The standardised incidences of proctitis were 3.1/10(5)/year (95% CI 1.9-2.5 cases/10(5)/year) in South Asians and 2.3/10(5)/year (95% CI 1.8 2.4 cases/10(5)/year) in Europeans. Ethnic groups had a similar disease distribution, except Sikhs in whom it was less extensive. Despite the similar disease distribution, South Asians had fewer operations and complications from UC than Europeans. There was a bimodal age specific incidence in Europeans, but not in other ethnic groups. First and second generation South Asians were at similar risk. Hindus and Sikhs have a significantly higher incidence of UC than Europeans in Leicestershire. PMID- 1307685 TI - The free hormone hypothesis and measurement of free hormones. PMID- 1307686 TI - Myocardial lesions induced after trauma and treatment. AB - In order to clarify the effect of trauma and treatment as stresses on myocardia, we examined histological changes of myocardia in victims who received various kinds of traumata and treatments. We also undertook a histochemical study for calmodulin, which we found useful in the diagnosis of early ischemia. Those who died shortly after stab wounds, traffic accident or head injuries, showed mild cardiac lesions such as contraction bands or fragmentation and mild diffusion of calmodulin, a marker for necrosis. A case with hemorrhagic shock after a traffic accident, involving intense resuscitation for 2 h, showed severe cardiac lesions such as contraction bands, hydropic change and subendocardial hemorrhage along with severe diffusion of calmodulin. In most of the instant death cases after falls, severe contraction band necrosis and severe calmodulin diffusion were observed. Myocardia of victims, who died several days after head injuries or traffic accidents, generally demonstrated distinct diffusion of calmodulin as compared to the mild and non-specific lesions detected by hematoxylin-eosin (H&E) staining. In cases of long-term survival in a state of brain death, calmodulin staining was very low, which was not always associated with the severity of the lesions on H&E staining. In cases with intensive or extended treatment, it appeared to be difficult to determine the cause-effect relationship between trauma and cardiac lesions or to distinguish the lesions due to extrinsic factors from those of disease. In some cases, calmodulin intensely stained the areas with hydropic appearance or hypereosinophilia, which may be related to calcium overload. PMID- 1307687 TI - Cleft lip with or without cleft palate in Shanghai, China: evidence for an autosomal major locus. AB - Orientals are at higher risk for cleft lip with or without cleft palate (CL +/- P) than Caucasians or blacks. We collected demographic and family data to study factors contributing to the etiology of CL +/- P in Shanghai. The birth incidence of nonsyndromic CL +/- P (Shanghai 1980-87) was 1.11/1,000, with a male/female ratio of 1.42. Almost 2,000 nonsyndromic CL +/- P probands were ascertained from individuals operated on during the years 1956-83 at surgical hospitals in Shanghai. Detailed family histories and medical examinations were obtained for the probands and all available family members. Genetic analyses of the probands' families were performed under the mixed model with major locus (ML) and multifactorial (MFT) components. The hypotheses of no familial transmission and of MFT alone could be rejected. Of the ML models, the autosomal recessive was significantly most likely and was assumed for testing three complex hypotheses: (1) ML and sporadics; (2) ML and MFT; (3) ML, MFT, and sporadics. None of the complex models were more likely than the ML alone model. In conclusion, the best fitting, most parsimonious model for CL +/- P in Shanghai was that of an autosomal recessive major locus. PMID- 1307688 TI - Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease. AB - We studied the topographic distribution of Alzheimer's disease (AD)-type pathologic changes in the brains of 25 presumed nondemented elderly individuals. Neurofibrillary tangles (NFT) and senile plaques (SP) were evaluated quantitatively in nine to 20 cytoarchitectural fields using thioflavine S, Alz 50, and anti-beta/A4 amyloid immunohistochemistry. Our observations suggest that (1) most individuals over the age of 55 have at least a few NFT and SP; (2) the topographic distribution of NFT and SP in nondemented elderly individuals follows a consistent pattern of vulnerability in different cytoarchitectural areas; (3) NFT occur most frequently in the entorhinal and perirhinal cortices and the CA1/subiculum field of the hippocampus, while neocortical areas are less frequently affected; (4) immunohistochemically defined subtypes of SP have distinct patterns of distribution. beta/A4 immunoreactive SP are present in neocortical areas much greater than limbic areas. Alz-50 immunoreactive SP are infrequent and limited to those areas that contain Alz-50-positive neurons and NFT. These patterns closely match the hierarchical topographic distribution of NFT and SP observed in AD, suggesting a commonality in the pathologic processes that lead to NFT and SP in both aging and AD. PMID- 1307689 TI - Sigmoidoscopy in general practice. PMID- 1307691 TI - The laryngeal mask airway in recovery. PMID- 1307690 TI - Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis. AB - Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in the steady state blood concentrations of chloroquine (range 36.6 to 3895 ng.ml-1) and its two main biotransformation products; the latter represented, respectively, 47.7% and 12.9% of the concentration of chloroquine. This finding shows the need for further studies in view of the known toxic effects of chloroquine and the inevitable accumulation due to the exceptionally long residence time of the compound and its metabolites. The main requirement, which has not yet been met, for adding chloroquine to the list of drugs for which therapeutic drug monitoring is useful, is the lack of information about its mechanism of action, and consequently the dose-effect relationships of its therapeutic and toxic actions. Regular ophthalmic examination, in particular, is strongly recommended. The relatively high concentrations of desethylchloroquine and bisdesethylchloroquine found during chronic treatment show the need for more information about the therapeutic value and adverse effects of the metabolites. PMID- 1307693 TI - Pharmaceutical ads in journals. PMID- 1307692 TI - Rupture of pseudoaneurysm during attempted US-guided compression repair. PMID- 1307694 TI - The injuries to JFK. PMID- 1307695 TI - Misuse of temazepam. PMID- 1307696 TI - Promoting sexual health. PMID- 1307697 TI - Promoting sexual health. PMID- 1307698 TI - Otosyphilis: a diagnostic and therapeutic dilemma. AB - Traditional treatment of otosyphilis with penicillin and corticosteroids has achieved hearing improvement; however, selecting which patients with a positive fluorescent treponemal antibody absorption (FTA-ABS) test will benefit from treatment remains a problem. In order to study this problem, 18 patients with cochleovestibular dysfunction of unknown etiology and positive syphilis serology were treated with intravenous penicillin and corticosteroids. In addition, lumbar puncture and human immunodeficiency virus (HIV) testing were performed on all patients. Hearing improved in 5 (31%) of 16 patients, tinnitus decreased in 11 (85%) of 13, and vertigo improved in 6 (86%) of 7. Factors associated with hearing improvement were hearing loss present less than 5 years, fluctuating hearing, and age less than 60. Improvement was unrelated to the severity of the loss or previous therapy. All patients with cerebrospinal fluid abnormalities, including two patients with HIV disease, had subjective improvements. A diagnostic and treatment protocol is presented. PMID- 1307699 TI - Helping Down Syndrome children to reach new heights: the role of the pediatric nurse. AB - Children with Down Syndrome have marked short stature, microcephaly, and muscle weakness. These deficiencies can be corrected by treatment with human growth hormone. Nurses caring for children with Down Syndrome will need to become familiar with the complexities of diagnosing growth hormone deficiency and treatment with synthetic growth hormone. Family teaching includes preparation for diagnostic testing, home assessment, injection technique, provision of information, and ongoing support of the family system. PMID- 1307700 TI - Impediments to clarity: an annotated glossary of rhetorical pratfalls and pitfalls. PMID- 1307701 TI - Intertester reliability of judgments of the presence of trigger points in patients with low back pain. AB - The purpose of this study was to determine the intertester reliability of assessments of the presence of trigger points in the region of the lumbar spine of patients with low back pain (LBP). A total of six trigger points described by Travell and Simons were studied. The trigger point examination procedures described by Travell and Simons were used by 12 physical therapists. Randomly paired therapists examined 50 patients for 197 trigger points. The Kappa coefficient, percent agreement, the observed proportion of positive agreement (Ppos), and the observed proportion of negative agreement (Pneg) were used to describe reliability. Kappa values ranged from .29 to .38. Percent agreement ranged from 76% to 79%. Ppos ranged from .43 to .52. The low Kappa and Ppos values suggest different therapists are unable to reliably determine when a trigger point is present in a patient with LBP. This study suggests the usefulness of examining for the presence of trigger points in patients with LBP should be questioned. PMID- 1307702 TI - Non-steroidal anti-inflammatory drugs and appendicitis in patients aged over 50 years. AB - In a retrospective study 84 patients aged > or = 50 years undergoing emergency appendicectomy were matched for age and sex with 84 randomly selected emergency admissions as controls. Of the former, 31 (37 per cent) were taking non-steroidal anti-inflammatory drugs. (NSAIDs) at admission, compared with nine (11 per cent) of the controls (P < 0.01). In the study group a suppression of the white cell count was identified on admission in those taking NSAIDs (mean 11.9 x 10(9) l-1) compared with those not (mean 14.8 x 10(9) l-1) (P = 0.007). This is the first reported association between appendicitis and NSAIDs. The relative risk by odds ratio was substantially increased at 6.5 (95 per cent confidence interval 2.1 8.8). An NSAID-related impairment of host defences leading to failure in the resolution of inflammatory episodes may explain this association. It is further postulated that the suppression of the white cell response may be a marker of such an effect. PMID- 1307703 TI - Collecting, communicating and using information: the educational issues. A report from the Royal College of Physicians Committee on Medical Information Technology. AB - Few of the major advances in information science and technology have yet been successfully introduced in health care. Their implementation could improve both quality of care and the working environment of clinicians, but this will not be achieved by investing in hardware and software alone. Investment in education is also required. PMID- 1307704 TI - Net calcium absorption in premature infants: results of 103 metabolic balance studies. AB - Net calcium absorption was evaluated in 103 low-birth-weight preterm infants by a 72-h balance technique. At birth the infants had a mean (+/- SE) gestational age of 30.9 +/- 0.2 wk and weighed 1.43 +/- 0.03 kg. When tested 3 wk later, their net calcium absorption averaged 58 +/- 1% with an intake of 80 +/- 2 mg Ca.kg body wt-1.d-1. Of the 103 infants, 58 had been fed low-birth-weight formulas supplemented with vitamin D. The remainder received banked human milk, of whom 34 were supplemented with vitamin D and calcium; 11 infants received no supplementation. Calcium absorption in the four subgroups did not differ significantly, with neither vitamin D supplementation nor supplementation with vitamin D and calcium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-130 mg Ca.kg body wt-1.d-1) with a zero intercept. Because vitamin D supplementation did not increase net calcium absorption, it is concluded that in preterm low-birth-weight infants calcium absorption proceeds by a nonsaturable route, with the transcellular, vitamin D regulated mechanism not yet expressed. PMID- 1307706 TI - Health promotion for older people. AB - Health promotion for older people, or preventive geriatrics, has the potential to transform people's lives by providing greater satisfaction and by reducing both physical and psychological ill health. General practitioners are key personnel in any health promotion programme but should, ideally, co-ordinate their activities with other health professionals. The basic tool for general practitioners is a screening programme for all older people and for people at special risk. PMID- 1307707 TI - [Problems relative to informed consent]. PMID- 1307705 TI - Management of the severely anemic patient who refuses transfusion: lessons learned during the care of a Jehovah's Witness. AB - OBJECTIVE: To present the case of a Jehovah's Witness with severe anemia and to review the religious philosophy of such patients, the ethical and medicolegal aspects of their care, and the therapeutic options available to clinicians. DATA SOURCES: A MEDLINE literature search (1980 to 1992) identified most studies. Other studies were selected from the bibliographies of identified articles. STUDY SELECTION: Selection of articles was limited to the history, philosophy, medicolegal and ethical issues, and clinical management of anemic Jehovah's Witnesses; a recent article on recommendations for red cell transfusion was also reviewed. CONCLUSIONS: A clear understanding of the philosophy of the Jehovah's Witnesses regarding blood transfusion and of the medicolegal and ethical aspects of their care is essential to clinicians who care for such patients. One must also be aware of the many alternative therapeutic options that can maximize oxygen delivery and minimize oxygen consumption. The insights gained from this review are applicable to any severely anemic patient who refuses blood transfusion. PMID- 1307708 TI - [A critical review of the history of the systems for staging colorectal cancer]. AB - A great debate is still open in literature about the available staging systems of colorectal cancer. Therefore, an historical analysis of the several systems suggested in the last decades was performed; pathological, clinicopathological and more recent score clinicopathological staging systems were evaluated. From this historical review it appears that subsequent modifications of various classifications allowed only for a poor improvement in predictivity. A more careful histopathological examination of surgical specimen and more exact information about involvement of other organs and tissues allow a correct classification of patients affected by colorectal cancer independently of the staging system used. PMID- 1307709 TI - [The diagnostic elements and therapy principles in thyroid cancer: the Pavia experience 100 years after Bottini]. AB - The diagnostic and operative management of thyroid cancer is controversial as the nature of the disease is heterogeneous in its growth rate, pattern of spread, and histological type. Therefore, surgery must be extensive enough to minimize the chances of recurrence and death. In the period 1962-1989, 159 thyroid cancers were observed. According to the histological type, 61 total thyroidectomies, 34 hemithyroidectomies with isthmusectomy, and 29 subtotal thyroidectomies were performed. Cervical lymph node dissection was performed in 55 patients. The 10 year postoperative survival rate was 70.59% with lymphadenectomy and 65.71% without lymphadenectomy. PMID- 1307710 TI - [Biliary tract surgery in patients of 70 and older: an assessment of our experience with 100 consecutive cases]. AB - A series of 100 consecutive patients aged 70 years and older having biliary tract lithiasis observed over a 19-year period (1970-1989) at the 1st Surgical Department of the University of Rome was analyzed in an effort to define morbidity and mortality. Eighty-eight patients underwent surgical treatment. Three patients died postoperatively (3.4%); 12 patients had local and 13 general complications. The highest incidence of complications occurred in patients with associated diseases and bacteriobilia. A long-lasting symptomatology involved a more frequent exploration of the common bile duct. Morbidity and mortality were not significantly related to the type of surgical procedure performed. Elective biliary tract surgery is a safe procedure even in aged patients. PMID- 1307711 TI - [Desmoid tumors of the abdominal wall]. AB - The authors report their experience in the management of desmoid tumors, rare benign neoplasias, locally aggressive and potentially recurrent after surgery. Etiopathogenetic, diagnostic, and therapeutic features of these tumors are analysed and the value of surgery as well as chemo- or radiotherapy is considered. PMID- 1307712 TI - [Diaphragmatic hernias due to "strain": apropos a case report]. AB - After a brief report on the pathophysiology of diaphragmatic hernias, the authors describe a case of strain diaphragmatic hernia. Considering the rarity and the difficulty to make an immediate diagnosis of this pathology, the authors stress diagnostic problems of strain chest pain and surgical treatment of strain diaphragmatic hernias. PMID- 1307713 TI - [Idiopathic retroperitoneal fibrosis]. AB - The authors, on the basis of a case recently observed dwell upon the natural history, the etiopathogenesis, and diagnosis of idiopathic retroperitoneal fibrosis. After confirming that medical therapy may be successful in selected cases only, different surgical procedures are analysed. It is concluded that outcome and prognosis of these subjects depend on early diagnosis. PMID- 1307714 TI - Use of the fiberoptic bronchoscopy in the elderly. AB - The authors emphasize the primary role fiberoptic bronchoscopy has for diagnostic and therapeutic purposes in the elderly affected by pulmonary disease. Safety, efficacy and tolerability of the method in the elderly are obtained through a preliminary and careful evaluation of the patients, either clinical or instrumental. PMID- 1307715 TI - [The optimal implantation of the peritoneal-jugular shunt with LeVeen valve]. AB - The authors underline the efficacy of peritoneovenous shunting with LeVeen's valve in the treatment of refractory ascites in cirrhotic patients. Selection and appropriate preoperative management of patients are essential to assure good immediate and long-term results. PMID- 1307716 TI - Spatial arrangement of the interpositorubral projection in the rabbit. A retrograde HRP study. AB - The objective of this investigation was to analyse the organization of rubral afferents from the cerebellar interpositus nuclear complex (NI) in the rabbit. Free HRP was employed as a retrograde tracer to identify the distribution patterns of labeled cells in the anterior and posterior interpositus nuclei. The interpositus projections distribute throughout nearly the entire contralateral red nucleus (RN) except for its rostralmost parvocellular region (RN-PA) which does not correspond to the usually distinguished parvocellular subdivision of the red nucleus (RN-P). The central and lateral regions of the posterior interpositus nucleus (NIP) project (nearly exclusively) to the medial region of the RN. The lateral region of the anterior interpositus nucleus (NIA) sends projections to both the lateral and medial regions of the caudal three-quarters of the RN. Thus, the lateral region of the RN appears to be under nearly exclusive control of NIA. The rostral one quarter of the RN receives cerebellar afferents from the NIP only and caudal pole of RN from the NIA exclusively. Comparison of labelling patterns indicates absence of topogrophic differentiation of projections from the NIP, whereas dorsoventral topography in the NIA can correlate to the rostrocaudal and mediolateral arrangement of the RN. Collectively, interpositorubral projections in the rabbit are similar to those in other species only in basic features. PMID- 1307717 TI - Permeability-related structures in developing and mature microvessels of the chicken optic tectum. AB - The mode and the temporal sequence of the modifications undergone by permeability related structures in the neural microvessels have been ultrastructurally and morphometrically investigated in optic tecta of 6, 14, and 18 incubation day (i.d.) chicken embryos and of 30 day chickens. Horseradish peroxidase was utilized as a permeability marker. The endo- and exocytosis-related structures (vesicles and vacuoles) and the interendothelial junctions remarkably change during development: the density of the vacuoles is decreased at the 14th i.d., while that of the vesicles becomes significantly low at the 18th i.d., both reaching lowest values in the chicken; the passage of the marker through the endothelial junctions begins to be hindered from the 14th i.d., parallel to the perivascular arrangement of astrocytic glia endfeet, and it is completely blocked at hatching time. The findings suggest that the optic tectum microvessels are permeable, and thus immature, in the early development and progressively acquire morphofunctional features of vessels provided with barrier devices during the pre and post-natal development of the brain. PMID- 1307718 TI - The vasopressin positive elements in the hypothalamic magnocellular nuclei of rats treated with histamine. AB - The vasopressin (AVP) positive elements of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, were investigated in 180 male rats through immunohistochemical, morphometric and statistical methods. The rats were subdivided in the next groups: 20 control rats; 40 rats treated with physiological saline intraperitoneal via (ip); 40 rats treated with physiological saline intracerebroventricular via (icv); 40 histamine (HA) treated rats, ip; and 40 HA treated rats, icv. The labeled nerve cells appear in the lateral part of the PNV and the SON of the control animals. These neurons have central nucleus and vasopressin positive cytoplasmic granulations. After the treatment with physiological saline, ip or icv, no alterations were observed. In HA treated rats, icv, numerous neurons strongly labeled were observed in these hypothalamic nuclei. Vasopressin positive nerve fibers and large droplets were also found both in the SON and in the PVN of these animals. The vasopressin positive material in the control rats and in HA treated rats, ip, is similar. The morphometric and statistical studies confirm these findings. The results are discussed in this paper. PMID- 1307719 TI - ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B cells. AB - Although closure of the ATP-sensitive K+ (K+ ATP) channel produced by glucose metabolism in the B-cell has been considered mediating the major signal for glucose-induced insulin release, evidences indicating the existence of the K+ ATP channel-independent, insulinotropic action of glucose have recently been accumulated. Namely, glucose stimulates insulin release by the B-cell with a full inhibition of the K+ ATP channel closure by diazoxide, a K+ ATP channel opener, provided cytosolic calcium is elevated. Glucose clearly elicits insulin release even if the K+ ATP channel is maximally inhibited by high concentration of sulfonylurea. In this case, glucose-induced insulin release is associated with net increase, not decrease, of K+ outflow, indicating glucose is opening K+ channels. Thus, closure of the K+ ATP channel is highly unlikely to be the mechanism responsible for the insulinotropic action of glucose under these conditions. The K+ ATP channel-independent glucose action is dependent upon physiological glucose concentration (2-30 mM) and the degree of cytosolic calcium elevation. The K+ ATP channel-independent, glucose-induced insulin release shows gradually increasing monophasic pattern which temporally resembles the second phase response of glucose-induced insulin release. The role of glucose metabolism in the K+ ATP channel-independent glucose action remains to be established. Glucose action at the B-cell can now be subdivided into two classes: one is the K+ ATP channel-dependent and the other is the K+ ATP channel-independent. The two branches may be mutually interrelated to cause normal, biphasic insulin secretion. PMID- 1307720 TI - Subcellular distribution of differently glycosylated forms of active and inactive renin in rat kidney: effect of sodium depletion and captopril treatment. AB - Distribution of differently glycosylated forms of active and inactive renin was investigated in fractions prepared by discontinuous density gradient centrifugation of rat kidney cortex homogenate. Concanavalin A (con A) chromatography separated active and inactive renin into three differently glycosylated forms in both cytosol and granule fractions: a minor con A unbound form (I), a loosely bound form (II), and the most predominant tightly bound form (III). After a long-term stimulation of renin synthesis and secretion by sodium depletion and captopril treatment the relative proportion of active renins I and II in granules significantly increased, while that of active renin III decreased. The relative proportion of inactive renins I and II in granule compared to cytosol fractions was significantly higher and that of inactive renin III was lower. The results indicate that glycosylation might have some relation to the rate of sorting of prorenin into the granules, or of its processing within granules. Alternatively, it might influence the rate of inactive renin release via the constitutive pathway. PMID- 1307721 TI - In vivo role of corticosterone in regulation of insulin receptors in rat adipocytes during hypokinesia. AB - The role of corticosterone in the changes of insulin receptors of rat adipocytes during hypokinesia was investigated. Three groups of adult male Wistar rats (1. intact; 2. adrenalectomized; 3. dexamethasone treated) were exposed to hypokinesia for various period. The plasma levels of corticosterone, insulin and glucose and the binding of insulin (125I-TyrA-14 monoiodoinsulin) to isolated adipocytes were determined. A significant increase of plasma corticosterone level and a decrease of insulin binding to adipocytes were found in rats exposed to hypokinesia for one day. After 3 and 5 days of hypokinesia the corticosterone level in plasma was decreased to the concentration observed in the control animals. Also the binding of insulin to adipocytes returned to the values found in control group. In adrenalectomized rats exposed to hypokinesia no changes of insulin receptors in adipocytes were noted. The treatment of rats with dexamethasone (both, the intact and adrenalectomize ones) resulted in a decrease of insulin binding in fat cells. These results showed that an increase of corticosterone in plasma after the short term exposure to hypokinesia or the injection of dexamethasone to intact or adrenalectomized animals are followed by the decrease of insulin receptors in adipocytes suggesting that glucocorticoids participate in the regulation of insulin receptors in adipocytes during short term hypokinesia. PMID- 1307722 TI - Interrelations between steroid hormone secretion and morphological changes of porcine corpora lutea at various periods of luteal phase. AB - Four types of porcine corpora lutea (CL) were excised at 4 various stages of the luteal phase. One part of corpora lutea was homogenized and the concentration of progesterone (P4), estradiol (E2) and androgens (A) was assayed in adequate extracts. Second part of luteal cells obtained from each of four types of CL was cultured as separate monolayers and steroid secretion was measured after 24, 48 and 96 h of culture. The concentration of P4 in homogenates of CL type 2 and 3 was twice as high as that in type 1, while a decrease to minimum level in type 4 was observed. In cultures, maximum increase in P4 production was observed after 24 h, being the highest in type 1 (2800% of initial P4 concentration) and type 2 (320%) while in types 3 and 4 no increase was observed. The contents of androgens (A) in CL homogenates increased 3 times in type 2 and 3 and finally decreased in type 4 as compared with type 1. In cultures, maximum increase in A production was observed after 24 h, being the highest in type 1 (640% of A concentration prior to culture), while in types 2, 3 and 4 it was about 200%. The content of E2 in homogenates of CL types 1 and 2 was very low, but increased to about 200% in type 3 and to about 2500% in type 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307723 TI - [Chronology of radiotherapy. 1900-1960. Selected chapters from the German language radio-oncologic literature. Volume 1: 1900-1925]. PMID- 1307724 TI - Biological signals generated by living organisms. PMID- 1307725 TI - 'Depletion' of ATP by 2-deoxyglucose: secretion by electroporated human neutrophils is not restored by readdition of ATP. AB - Studies of intracellular signal transduction are facilitated by the use of permeabilized cell systems, which permit the ready manipulation of the cytosol. These model systems have helped to define the roles that small solutes, particularly Ca2+ and nucleotides, play in stimulus-response coupling. In circumstances where the full depletion of intracellular ATP contents is required, some investigators have resorted to prior treatment with metabolic toxins, with the expectation that the role of ATP in signal transduction could then be more unambiguously studied. However, in the work reported here, we found that treatment with 2-deoxyglucose (2-DOG) irreversibly altered the cells: when poisoned human neutrophils were then permeabilized, the cells failed to degranulate well in response to Ca2+, and their sensitivity to Ca2+ could not be recovered by the readdition of ATP. Inhibition of secretion by 2-DOG was most pronounced when low concentrations of Ca2+ were used as the stimulus. Preincubation of the cells with only 1 mM 2-DOG for 10 min at 37 degrees C (prior to washing and permeabilizing the cells) was sufficient for maximal inhibition. Even without preincubation, high concentrations of 2-DOG directly inhibited secretion. The refractory nature of poisoned cells was not restored by the presence of Mg2+ and/or ATP. The protein kinase C agonist phorbol myristate acetate also did not restore sensitivity of secretion to Ca2+. Addition of ATP and/or GTP to the permeabilization medium (to maximize penetration of the nucleotides) failed to restore sensitivity; tracer studies demonstrated that these conditions were adequate for repletion of the nucleotide pool. These data indicate that human neutrophils poisoned with 2-DOG were irreversibly altered, such that restoration of the putative deficiency (ATP) was without effect. Experiments in which such preincubation measures are employed should be viewed with caution. PMID- 1307726 TI - GABA activity in dispersed bovine pineal cells: effect on serotonin release and calcium and chloride uptake. AB - The presence of gamma-aminobutyric acid (GABA) and peripheral and central benzodiazepine receptors in the mammalian pineal gland prompted the examination of GABAergic transmission in dispersed bovine pineal cells. The effect of GABA on 3H-serotonin (5HT) release was examined in bovine pineal cells. GABA, by acting through GABA B receptor subtype, decreased 5HT release and by acting through GABA B, and presumably through GABA A receptor subtypes, inhibited depolarization induced 45Ca2+ uptake in bovine pinealocytes. GABA, by acting on GABA B as well as on GABA A receptors, prevented the 5HT2- or 5HT1C-mediated stimulatory effect of serotonergic agonists on calcium uptake in pineal cells. GABA augmented 36Cl- uptake by bovine pineal cells. These results are interpreted to indicate that, by regulating the release of 5HT, GABA may modulate the synthesis and action of melatonin. PMID- 1307727 TI - [Errors in the medical treatment of common diseases. A serious problem of Public Health]. PMID- 1307728 TI - [Patterns of therapeutic prescription in diarrhea and acute respiratory infections in 2 health care institutions: SS and IMSS]. PMID- 1307729 TI - [AIDS]. PMID- 1307730 TI - [Advances in diagnostic and therapeutic criteria in acute respiratory infections]. PMID- 1307731 TI - [Advances in diagnostic and therapeutic criteria in acute diarrhea]. PMID- 1307732 TI - [Mortality risk factors in acute respiratory tract infections and diarrhea in children younger than 5 years old]. PMID- 1307733 TI - [Quantification of menstrual bleeding in women using intrauterine devices (IUDs)]. AB - A study in the changes of menstrual blood loss produced by the of 11 different intrauterine devices (IUDs) in 319 voluntary women attending a voluntary program for Family Planning at the Instituto Mexicano del Seguro Social (IMSS). The results showed that two IUDs increased bleeding above 80 mL in the case of Lippes Loop D and the copper T 380. The following IUDs: Cu T 200 and 220, as well as ML 250 increased blood loss moderately; copper 7 produced a slightly higher blood loss (not statistically significant) "T" IUDs liberating progesterone or progestagens (Nor 8; Nor 2; Net 10) all produce a significant decrease of the menstural flow, reaching 93.5% (of the control value) in women using "T" IUDs liberating 8 micrograms of Levonorgestrel. Excessive bleeding in women with IUDs (over 80 ml) is checked significantly by the use of non-steroid anti-inflammatory prostaglandin synthesis' inhibitors such as 500 mg of mefenaminc acid or 250 mg of Naproxen thrice daily for 5 days. PMID- 1307734 TI - [The French foundations in Mexico. The scientific commission]. PMID- 1307735 TI - Peptide growth factor interactions in embryonic and fetal growth. AB - Peptide growth factors are expressed by multiple tissues in the animal and human embryo and fetus. They undergo specific interactions which control the rate of cellular proliferation, tissue differentiation and the induction of specific morphogenic events such as mesoderm formation in the embryo. Biologic control may not only be exerted at the level of growth factor synthesis and receptor expression but by the sequestration and storage of growth factors by extracellular matrix molecules. In the case of insulin-like growth factors (IGFs), storage maybe mediated by attachment to specific IGF-binding proteins which may additionally modulate biological potency. Basic fibroblast growth factor (basic FGF) and transforming growth factor-beta (TGF beta) directly bind to glycosaminoglycan molecules. Release of growth factors from these stores may be by local proteolytic action. A sequential expression of basic FGF, IGF-II and TGF beta occurs in the ovine fetal epiphyseal growth plate as chondrocytes progress from a proliferative to a postmitotic, hypertrophic state. Cellular phenotype may be largely explained by the relative amounts of these autocrine growth factors within the growth plate. PMID- 1307736 TI - Understanding the different phases of fetal growth. AB - Fetal growth was studied in 78 newborns who had serial scans in pregnancy. Weight at birth correlated with growth in the first 2 trimesters but better with the growth between 28 and 32 weeks. The correlations for weight at growth cessation were better than those for weight at birth. Crown-heel length at cessation did not correlate with fetal growth in the first 2 trimesters. Maternal weight increase correlated with fetal weight and crown-heel length but not with head circumference at cessation. Maternal prepregnancy weight correlated with fetal growth between 28 and 32 weeks, but not with fetal growth in the second trimester. A negative correlation was found between estimated duration of growth cessation and relative head circumference at birth. PMID- 1307737 TI - Estimation of fetal weight by ultrasound. AB - Estimation of fetal size by ultrasound has supported two recent concepts of fetal growth. Firstly, the normal weight gain is constant from 28 weeks of gestation until several weeks after term; about 27 g/day. Secondly, the average weight of fetuses born preterm is lower than the average weight of fetuses of the same gestational age who remain in utero. This means that up to 40% of infants born at 28-30 weeks of gestation are small-for-gestational age, when related to the biological optimum. Unfortunately, the test-retest variation of fetal weight estimation is as much as 50% of the standard deviation of the gestational-age specific fetal weight distribution. This means that fetal growth has to be followed for many weeks to document statistically significant deviations. No study has, as yet, demonstrated the value of this approach to distinguish between intrauterine growth retardation and growth along low centiles by fetuses of reduced growth potential. PMID- 1307738 TI - Recent aspects of steroid biosynthesis in male sex differentiation. Clinical studies. AB - Recent discoveries in molecular biology have much clarified the regulation and function of steroid-converting enzymes. Most progress has been made in the area of cytochromes, which regulate the side chain cleavage of cholesterol (P-450 SCC) and the 17 alpha-hydroxylase and 17,20-desmolase (or 17,20-lyase) activities (P 450 17 alpha), as well as in 3 beta-hydroxysteroid dehydrogenase. Nevertheless, there are some discrepancies between fundamental knowledge and clinical experience, which are difficult to understand: why is it for example possible that cases with 'pure' 17 alpha-hydroxylase or 17,20-desmolase deficiency exist, when there is only one cytochrome regulating both steps? After a brief review of clinical and biochemical findings in the various defects of testosterone biosynthesis, a case is discussed, which is of interest in this respect. This XY patient with female external genitalia, who has been shown to have compound heterozygous mutations, had 'pure' 17,20-desmolase deficiency up to adolescence, but additional 17 alpha-hydroxylase deficiency with hypertension developed thereafter. From this observation, it has to be concluded that as yet unknown, possibly age-dependent modulating factors exist, which influence the activity of the cytochrome. Also the estrogen replacement given to the patient might have played a role in this change. PMID- 1307739 TI - Genes involved in androgen biosynthesis and the male phenotype. AB - A series of enzymatic steps in the testis lead to the conversion of cholesterol to the male sex steroid hormones, testosterone and 5 alpha-dihydrotestosterone. Mutations in any one of these steps are presumed to alter or block the development of the male phenotype. Most of the genes encoding the enzymes involved in this pathway have now been cloned, and mutations within the coding regions of these genes do, in fact, block development of the male phenotype. PMID- 1307740 TI - Cloning and mutational analysis of SRY. AB - A candidate for the male sex-determining gene has recently been isolated. This sex-determining gene (SRY) has been found to be mutated in some individuals with failed testis development, and, in mouse transgenesis, the SRY murine homologue (Sry) causes female-to-male sex reversal. The cloning of SRY should facilitate the characterisation of other genes in the testis-determining pathway and provide information on the mechanism of mammalian developmental decisions. PMID- 1307741 TI - Role of the androgen receptor in male sexual differentiation. AB - The two androgens responsible for all aspects of male sexual differentiation are testosterone and dihydrotestosterone. The action of both these steroids is mediated by a specific intracellular receptor, the androgen receptor, which is a member of the nuclear receptor superfamily. The androgen receptor gene has been cloned and is located on the X chromosome at Xq11-12. Mutations of this gene have been found in subjects with both complete and partial androgen insensitivity. In a study of 27 subjects with the androgen insensitivity syndrome, we have identified mutations in 14, using a rapid mutation screening assay. The same technique has also been used to determine carrier status in an affected family. We have also identified a mutation in two brothers who show perineal hypospadias as the only evidence of undervirilisation. Familial severe hypospadias should therefore be included as part of the phenotypic spectrum of partial androgen insensitivity. The study of naturally occurring mutations of the androgen receptor gene is providing further information on the function of the androgen receptor and its role in normal male sexual differentiation. PMID- 1307742 TI - Comparison of epidemiological data on congenital hypothyroidism in Europe with those of other parts in the world. AB - The actual worldwide incidence of congenital hypothyroidism (CH) is based on the results of screening in parts of the world where screening is mandatory, i.e. most of Europe, USA, Canada, Cuba, Australia, New Zealand and Japan. In other parts of the world, some indications are given by the results of pilot studies. In Europe, mean overall incidence (1985-1990) for the countries included in our inquiry is 1/3801--in each country for the same period: Austria 1/3,930, Belgium 1/3,750, Czechoslovakia 1/6,037, Denmark 1/3,777, Finland 1/3,969, France 1/4,132, FRG 1/3,827, Greece 1/3,314, Hungary 1/5,632, Israel 1/3,152, Italy 1/3,150, The Netherlands 1/3,723, Norway 1/3,069, Portugal 1/3,139, Spain 1/3,216, Switzerland 1/3,913, UK 1/3,398 and Turkey (pilot study 1989-1992) 1/2,943. In comparison, the figures for the USA for the whole country are similar for the mean overall incidence (1988-1990): 1/4,119. But large variations exist between the states, the reasons of which are perhaps related either to technical problems or to the ethnic background in each state. In Canada and Japan, modifications of screening procedures have led to similar figures for the last years in our possess, Canada (1986-1988) 1/3,884 and Japan (1990) 1/3,856. The figures (mean overall incidence) for Cuba (1987-1991) 1/2,325, for Australia (1985-1990) 1/1/3,331 and for New Zealand (1987-1990) 1/4,496 are quite comparable. So in these countries where the screening is established, no great variations are noted as in certain parts of the world with pilot studies: Argentine (Buenos Aires; 1985-1990) 1/4,407, Chile (1991-1992) 1/2,514, Brazil (Porto Alegre; 1987-1991) 1/4,429.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307743 TI - School achievement in children with hypothyroidism detected at birth and search for predictive factors. AB - Neonatal screening of hypothyroidism started in 1975, and now sufficient hindsight is gained to assess school results in children with hypothyroidism and compare them to IQ tests. From the 85 cases of hypothyroidism detected in the Midi-Pyrenees area, 40 have enrolled in or finished primary school and 18 started secondary school. School achievement was assessed by school test results in French and mathematics using specific grids for each class and by retention rates. These results were compared to control groups. The hypothyroid group obtained identical results in French to those of the control groups but scored lower in mathematics. Grade retention rated higher in hypothyroid children (20%) than in the control groups (12.5%), especially in the first primary school grade. The search for predictive severity factors revealed significant differences between the grade repeater group and the nonrepeater group: more cases of athyrosis (75 vs. 25% for ectopia), lower T4 levels at birth, lower bone surface, lower IQ at 4 and 7 years, neurological troubles of fine motricity and coordination, and lower socioeconomic level. These results should shortly be taken into consideration in order to isolate a group at risk and undertake specialized care to improve school results in this group. PMID- 1307744 TI - Testicular adrenal-like tissue in a patient with 17 alpha-hydroxylase deficiency. AB - Testicular adrenal-like tissue (TALT) have been observed in patients with congenital adrenal hyperplasia, and is usually associated with 21-hydroxylase deficiency; in 3 cases with 11 beta-hydroxylase deficiency. We report a case of male pseudohermaphroditism with 17 alpha-hydroxylase deficiency (17OHD) who also had TALT. To our knowledge, this is the first report about the association of 17OHD and TALT. Also, the patient had high levels of serum aldosterone--an unusual finding in patients with 17OHD. A possible pathogenic mechanism is discussed. PMID- 1307745 TI - Comparison between short- and long-term insulin-like growth factor response to recombinant human growth hormone. AB - Eight growth-hormone-deficient children were treated with recombinant human GH (rhGH). Results of the short-term metabolic response to rhGH performed at the start of therapy during a 5-day introduction period and long-term results on growth were analyzed. We could not find any correlation between the effects on the short-term metabolic test and the growth response during long-term therapy, namely between the urea and insulin-like growth factor-I response during the short test and the increase in growth velocity. The short-term test is not a good predictor of the long-term response. PMID- 1307746 TI - The diagnostic value of integrated growth hormone secretion studies shorter than 24 hours in normal- and short-growing children. AB - Spontaneous growth hormone (GH) secretion is evaluated by measurement of the 24 hour integrated concentration of GH (24-hour IC-GH), a major diagnostic procedure, or by shorter protocols such as monitoring 6 h during sleep. We have evaluated several possibilities for shortening the procedure by comparing the results of an abbreviated procedure to the 24-hour IC-GH studies. The study population consisted of 50 children with classic GH deficiency (group GHD), determined by provocative testing, and 45 children who had a subnormal secretion of GH (group N), determined by low 24-hour IC-GH but normal GH provocative tests. Twenty-two children of normal height and stature served as a control group. All the children were prepubertal, while there was no overlap between the lower 5th percentile of the 24-hour IC-GH of the control subjects (3.3 micrograms/l) and the upper 97th percentile of the 24-hour IC-GHs of the N and GHD groups (2.9 and 2.7 micrograms/l, respectively), there was a considerable overlap between the IC GH of control subjects and that of the GHD and N groups measured in all the abbreviated blood withdrawal protocols, except for the 10-hour daytime and the 12 hour nighttime protocols of the GHD patients. It should be noted that there was only a small overlap between the control and the GHD groups during the 12-hour daytime protocol. We have found that the longer the blood collection period the greater the sensitivity and the specificity. We conclude that the 24-hour IC-GH test is the best diagnostic tool for identifying children with subnormal GH secretion. PMID- 1307747 TI - Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism. AB - Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/ SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level. PMID- 1307748 TI - First-phase insulin release in adult cystic fibrosis patients: correlation with clinical and biological parameters. AB - Adult patients with cystic fibrosis (CF) are at high risk for developing insulin dependent diabetes mellitus. Therefore, the fast insulin release (FIR) to intravenously administered glucose was measured in 23 adult CF patients. The influence of the clinical parameters and type of gene deletion on the amplitude of the FIR, defined by the sum of the 1st- and 3rd-minute insulin concentrations was analyzed. In 11 of the 18 normoglycemic patients with exocrine pancreatic insufficiency and the 3 nontreated diabetic CF patients studied, an FIR value lower than the 3rd percentile was found. The female patients had higher mean FIR values than the male patients (62.8 +/- 39.6 vs. 27.9 +/- 17.9 mU/l; p < 0.05). No influence of age, body mass index, or pulmonary or liver involvement on the FIR was found. Subjects heterozygous for the delta F508 deletion had a similar insulin response as homozygous patients. The FIR level correlated negatively with the basal glucose level (r = 0.4; p < 0.001). In conclusion, 61% of the adult nondiabetic CF patients with exocrine pancreatic insufficiency presented a loss in acute insulin response, which could not be predicted by clinical or genetic parameters. PMID- 1307749 TI - Studies on the association of NIDDM in Japanese patients with hyperthyroid Graves' disease. AB - We attempted to analyze the association of hyperthyroid Graves' disease with non insulin-dependent diabetes mellitus (NIDDM). Forty-nine patients (23 males and 26 females; 7.6%) of a total of 647 patients with hyperthyroid Graves' disease had NIDDM, several years before or after Graves' disease was diagnosed. Only 1 patient had insulin-dependent diabetes mellitus. Compared with the general Japanese population (n = 9,133), the incidence of NIDDM (n = 348; 3.9%) in patients with Graves' disease was higher in all age groups. Only 4 patients (8.2%) of the 49 hyperthyroid patients with NIDDM had a history of being overweight (body mass index > 25). In contrast, 276 (79.9%) of the 348 diabetic patients were currently or previously overweight. Moreover, the incidence of a family history of diabetes (13 of the 49 hyperthyroid Graves' patients with NIDDM; 26.5%) was also lower in the patients with NIDDM in the general Japanese population (50% incidence). The male:female ration in patients with Graves' disease and NIDDM was 1:1.1; much different from that in the total Graves' disease population (1:4.1). Analysis of the HLA loci A, B, C, DR and DQ (35 determinations) in 35 hyperthyroid patients with NIDDM and in 386 subjects from the general population revealed a highly significant difference between them in the incidence of HLA-Cw4, -DR2, -DQw1, -DQw3 and -DQw4. This study suggests that there was an association of Graves' disease with NIDDM. A significant association of HLA-DR and -DQ loci was observed in hyperthyroid Graves' patients with NIDDM. PMID- 1307750 TI - Remaining abstracts of the 33rd annual conference of the Indian Society of Gastroenterology. New Delhi, November 6-8, 1992. PMID- 1307751 TI - Is preoperative fasting necessary? AB - The effects of fasting and of histamine (H2) antagonists on gastric volume and acidity were studied in 56 baboons undergoing various surgical procedures under general anesthesia and randomly allocated into 4 groups; group A--fasted for 14 hours; group B--given 100-120 ml of water 3 hours before surgery; groups C and D- also given 100-120 ml of water 3 hours before surgery; in addition, the former received cimetidine 10 mg/kg IM and the latter ranitidine 1.5 mg/kg IM 30-40 minutes before anesthesia. There were no significant differences between groups A and B with respect to the gastric volume and pH. Both ranitidine and cimetidine significantly (P < 0.02) reduced gastric volume and increased gastric pH. Thus, prolonged withholding of oral fluids does not reduce the gastric volume or increase gastric pH. H2-antagonists are effective in reducing both gastric residual volume and pH. PMID- 1307752 TI - An ultrasound study of the effect of chronic lead exposure on endometrial cycle changes in the female cynomolgus monkey. AB - The effect of up to 10 years of lead (Pb) exposure (1500 micrograms/kg BW/day) on endometrial cycle changes in adult cynomolgus monkeys (n = 30) were examined by real-time ultrasound. Pb exposure had no effect on peak serum estradiol (E2) or progesterone (P4) concentrations, menstrual cycle length, and endometrial response to gonadal steroids as determined by ultrasound. PMID- 1307753 TI - Chronic Pseudomonas aeruginosa endobronchitis in rhesus monkeys: I. Effects of pentoxifylline on neutrophil influx. AB - Host defense abnormalities in cystic fibrosis (CF) against Pseudomonas aeruginosa (PA) lead to excessive neutrophil influx into the infected lungs, resulting in pulmonary complications. We have developed a rhesus monkey model of chronic PA endobronchitis by intrabronchial instillation of PA-embedded agar beads, utilizing flexible fiberoptic bronchoscopy. Treatment of infected monkeys with pentoxifylline suppressed neutrophil influx and ameliorated pulmonary damage. The results suggest a method by which neutrophil influx and pulmonary damage in CF patients can be managed or prevented. PMID- 1307754 TI - A non-invasive technique for the control of intestinal parasites in rhesus macaques (Macaca mulatta). AB - Control of intestinal parasites is a major concern in maintaining the health and well-being of captive primates. This study established that percutaneous application of ivermectin was as effective as subcutaneous administration for the control of nematodes in captive rhesus macaques. The method is less intrusive than the standard subcutaneous or oral delivery routes and did not adversely affect the health of any of the study subjects. PMID- 1307755 TI - A jejunal pouch technique in the rhesus monkey and related clinical observations. PMID- 1307756 TI - Gestational diabetes mellitus in a cynomolgus monkey with group A streptococcal metritis and hemolytic uremic syndrome. AB - Gestational diabetes mellitus was diagnosed retrospectively in a ten-year-old female cynomolgus monkey. The mother developed severe purulent group A streptococcal metritis resulting in fetal sepsis. After parturition, the mother died from signs consistent with hemolytic uremic syndrome. PMID- 1307757 TI - Cellular responses of vervet monkeys (Cercopithecus aethiops) experimentally infected with Leishmania major. PMID- 1307758 TI - Spontaneous cardiomyopathy resembling acute rheumatic heart disease in an owl monkey. AB - A wild-caught male Aotus vociferans died spontaneously during quarantine. Histologic examination of the heart showed several small myocardial arteries replaced with fibrinoid necrosis and adjacent inflammation that included lymphocytes and large histiocytic cells. Less often, similar inflammatory foci were observed in the myocardium interstitium. The lesions observed in the heart of the owl monkey resembled Aschoff bodies. PMID- 1307759 TI - Oral squamous cell carcinoma in capuchin monkeys (Cebus apella). Report of two cases. AB - Two neoplasms were observed in two feral male Cebus apella monkeys of approximately 12 and 14 years of age. Histologically, the tumors were well differentiated squamous cell carcinomas, one affecting the soft and hard palates reaching the nasal cavity and the other involving the oral cavity floor and the inferior maxillar. PMID- 1307760 TI - Pasteurella haemolytica infection in a Goeldie's monkey. AB - An adult male Callimico goeldii died spontaneously. At necropsy, small whitish foci were found randomly distributed on the liver surface. Histologically, the foci were composed of mixed inflammatory cells with predominant polymorphonuclear cell infiltration and central areas of necrosis. Microbiological cultures revealed a Gram-negative coccoid-bacilli with bipolar staining. Biochemical analysis revealed that the microorganism was Pasteurella haemolytica. PMID- 1307761 TI - Arterial blood pressure values in children and adolescents in the Lublin population. Epidemiological studies. AB - The frequency of arterial hypertension occurrence in the adult population is estimated at 10-20%. In the last decade attention has been called to hypertension in children and adolescents. The purpose of the present study was to determine the arterial blood pressure in the studied age groups of children and adolescents in the elementary and secondary schools in Lublin, and to establish the prevalence of hypertension in this population group. PMID- 1307762 TI - Liver schistosomiasis in Kuwait. Clinical presentations and pathological findings. AB - This is a study on hepatic schistosomiasis including twenty eight cases, diagnosed over nine years period in a district general hospital in Kuwait. The clinical and histological picture in relation to the type of parasite is reviewed and the role played by S. haematobium species in the pathogenesis of liver disease affecting the immigrants in Kuwait is pointed out. The significance of the incidental finding of the schistosomal eggs in the liver and of the associated HBV infection is discussed. The topographic relation of schistosomal eggs and the surrounding granuloma to the fibrosis is described and these findings are related to the morphogenesis of this lesion. PMID- 1307763 TI - Malarial placental infection and low birth weight babies. AB - Two hundred and fifty six mothers and their newborns were subjected to clinical and haematological tests for the evidence of malaria. Placentae of these were examined histopathologically for malarial parasites and malarial pigment. Forty six placentae showed scanty malarial pigment ingested by monocytes. These appearances were associated with focal syncytial necrosis and proliferation of cytotrophoblastic cells. Plasmodium falciparum was found in cord blood of six cases. The mean weight of newborns born to mothers having no evidence of malarial placental infection was 2,763 kg, while mean weight of newborns belonging to infected placentae was 2,143 kg. The difference was highly significant. PMID- 1307764 TI - Comparison of the effects of Salbupart and Partusisten on the serum levels of insulin, glucose, sodium and potassium in pregnant women. AB - The effect of tocolytic treatment with Salbupart and Partusisten in imminent premature labour on the serum levels of insulin, glucose, sodium and potassium was studied after 24 hours, and in some cases after 48 and 72 hours from the beginning of intravenous tocolytic treatment. The control group comprised healthy pregnant women receiving no tocolytic treatment. Statistical analysis showed that Salbupart and Partusisten raised the levels of insulin and glucose in the serum in pregnant women, but Salbupart increased more the insulin level and the raised levels of insulin and glucose persisted longer after Salbupart. No effect of these preparations on the serum levels of sodium and potassium in the studied pregnant women was noted. PMID- 1307765 TI - Certain aspects of interaction between sodium valproate and other anticonvulsant drugs in the therapy of epilepsy in children. AB - The serum valproate (VPA) concentration and the clinical effects of polytherapy with other antiepileptic drugs: phenobarbital (PB), clonazepam (CZP), diazepam (DZ), clobazam (CLO), ethosuximide (ESX) were estimated. VPA serum levels were reduced when this drug was combined with phenobarbital. Clobazam given together with valproate led to an increase in the serum concentration of the former drug. VPA serum levels were without significant changes when the drug was combined with either ethosuximide or 1-4-benzodiazepines. The best therapeutical effects were found after polytherapy sodium valproate with ethosuximide and clobazam in primary generalized seizures. PMID- 1307766 TI - Salbupart effect on rabbit heart and brain. AB - In connection with the widespread use of the product Salbupart POLFA in the treatment of imminent premature labour the effect of this medicament on rabbit fetuses was studied. In all, 29 fetuses were examined, particularly with histological examination of the heart and the central nervous system. No harmful effects of the medicament on these organs was found. In the fetal central nervous system Salbupart produced more intense staining of myelin sheaths by Heidenhain's method which may suggest earlier maturation of the brain. PMID- 1307767 TI - The effect of Salbupart on the value of placental perfusion pressure in extracorporeal experiment. AB - The purpose of the study was determination of the perfusion pressure as an expression of the resistance of placental vascular bed after administration of various doses of Salbupart. In a series of 29 experiments with extracorporeal perfusion of the fetal part of the placental from spontaneous labours after physiological pregnancy it was observed that the medicament given in one dose reduced the vascular resistance in the afterbirth. A beneficial spasmolytic effect of Salbupart may be expected in certain cases of pathological pregnancy associated with increased resting tonus of the placental vessels. The pharmacological management for stimulation of placental adenyl cyclase may be treated as supplementation of deficient endogenous catecholamines enhancing the adaptation mechanisms of the fetus and placenta. PMID- 1307768 TI - Conn's syndrome or Litynski-Conn syndrome? PMID- 1307769 TI - Aleksander Rytel. PMID- 1307770 TI - The Ujazdowski Hospital during the Nazi occupation (the Republic of Ujazdow, oasis of all that is Polish, refuge, scientific centre and Alma Mater). PMID- 1307771 TI - Experimental studies of pancreatic transplantation after freezing and thawing. AB - The successful rat pancreatic transplantation, after 30 minutes cryopreservation at -80 degrees C, is presented with the normal graft function till the 6th postoperative day maximum. The freezing device used by the authors is shortly described. The choice of optimal freezing and thawing parameters is discussed. Organ freezing is a hopeful method which could serve to preserve the solid organs for a long period of time. Our former experimental research showed that slow freezing (1-2 degrees C/min) and fast thawing (> 100 degrees C/min) had produced less damage to the pancreas of the rat [1]. Recently we performed rat pancreatic transplantation after freezing and thawing the donor pancreas with the parameters mentioned above. PMID- 1307772 TI - C-myc gene expression in stage I endometrioid adenocarcinoma of the uterus. AB - Expression of a c-myc proto-oncogene product known as p62 (c-myc) was studied in 18 cases of stage I endometrioid (typical) adenocarcinoma of the uterus by immunohistochemistry and correlated with mucin production and other pathologic features. Cytoplasmic staining of tumor cells for c-myc product was seen in all cases and nuclear staining in three cases. Endometrial stromal cells were invariably negative and myometrial nuclear staining was seen in three cases. Within the tumor itself, whereas intense staining was frequent in high grade tumors with deep myometrial and vascular invasion, faint to moderate staining was frequent in well differentiated tumors with superficial myometrial invasion. A general tendency was also seen for greater staining in the myometrial component of the tumor than in tumor located in the endometrium. Whereas staining in the latter was frequently patchy in distribution, c-myc expression was invariably uniform in the myometrial component. Mucin production was somewhat greater in endometrial than myometrial components but did not correlate with c-myc expression or other pathologic features. This study demonstrates that c-myc is variably expressed in endometrial carcinoma and high c-myc expression can be associated with populations of tumor cells selectively capable of myometrial and vascular invasion. PMID- 1307773 TI - Simultaneous determination of coagulation and fibrinolysis parameters for diagnostics of disseminated intravascular blood coagulation (DIC). AB - A diagnostic method is described for determining the parameters of the human blood plasma coagulation and fibrinolysis by turbidimetry. Diluted plasma with thrombin and streptokinase is mixed to initiate clot formation and subsequent clot dissolution. The resultant profile of absorbance versus time is analysed to determine six parameters: plasma coagulation time, the rate of coagulation, fibrinogen concentration, the rate of fibrinolysis, fibrin clot half-lysis and lysis time. The assay is precise, sensitive and requires 0.1 ml plasma. The method has a good correlation with generally accepted haemostatic tests and allowed us to recognize the stage of DIC syndrome for less than 10 minutes. This new approach was successfully applied for studying the haemostasis in patients with acute intestinal infection. PMID- 1307774 TI - Diagnostic value of some subjective and objective symptoms of gastric ulcer. AB - Some subjective and objective symptoms, that are believed to be specific of peptic ulcer, were analyzed in 425 patients with endoscopically confirmed gastric ulcer. It was noted that the pain syndrome may have variants while pain after meals remains a typical sign of gastric ulcer. But asthenic habitus, tendency to sinus bradycardia and arterial hypotension, the absence of a coated tongue, and the tendency to erythrocytosis and decelerated ESR were not typical for the observed patients. The results suggest that some traditional concepts of typical clinical picture of peptic ulcer should be revised. PMID- 1307776 TI - The influence of hemodialysis on plasma fluoride. AB - Since storage of fluoride in the skeleton has been blamed as an etiologic factor in the development of renal osteodystrophy, we studied the influence of hemodialysis on plasma fluoride levels in 17 patients with chronic renal failure on regular hemodialysis. The fluoride level in dialysate was found to be 19 micrograms/L, and 7.2 +/- 1.2 micrograms/L in healthy persons. Before hemodialysis, the mean fluoride level was 117.3 +/- 8.4 micrograms/L. It decreased to 113.3 +/- 8.5 micrograms/L at the first hour of dialysis and to 105.7 +/- 8.6 micrograms/L at the end of the dialysis, with no significance. We suggest that it would be appropriate to use "very low-fluoride" dialysate in order to reduce the plasma fluoride levels in patients with chronic renal failure. PMID- 1307775 TI - Changes in human plasma dopamine-beta-hydroxylase activity after ketamine and halothane anesthesia. AB - The intravenous administration of ketamine hydrochloride to fifteen patients undergoing surgery produced no change in circulating plasma dopamine-beta hydroxylase (DBH), although it produced a significant increase both in systolic blood pressure (BP) and diastolic BP during anesthesia. Halothane anesthesia that depress BP also produced no change in plasma DBH activity. PMID- 1307777 TI - Therapeutic effect of gevilon in patients with hyperlipoproteinaemia. AB - Authors examined 46 patients with hyperlipoproteinaemia divided according to hyperlipoproteinaemia type II A, II B, IV. After one month of isocaloric diet the patients were given a single night gevilon dose of 900 mg for a period of 3 months. After therapy we examined lipid metabolism, liver and kidney function, carbohydrate metabolism, hematopoietic system and water--electrolyte balance. In all groups increased levels of cholesterol, beta-lipoproteins and triglycerides were significantly reduced after 3 months of gevilon treatment. In all patients the HDL/LDL ratio increased close to normal values. No impairment of kidney or liver function hematopoietic system and electrolyte balance after 3 months of treatment were noted. Because gevilon is easy to apply and has a limited number of side effects, it is very readily taken by the patients who have lipid balance disorders. PMID- 1307778 TI - Attitudes of Kuwaitis towards disabled persons. PMID- 1307779 TI - [Biological test procedures. Reports from the Biotest Status Seminars in 1989 and 1992]. PMID- 1307781 TI - [Introductory address to the 1st Biotest Status Seminar]. PMID- 1307780 TI - [Rainbow trout and zebrafish, two models for continuous toxicity tests: relative sensitivity, species and organ specificity in cytopathologic reaction of liver and intestines to atrazine]. AB - In order to elucidate cytopathological alterations in hepatic and intestinal cells, immature rainbow trout (Oncorhynchus mykiss) were exposed for five weeks to 10, 20, 40, and 160 micrograms/l of the herbicide atrazine (2-chloro-4 ethylamino-6-isopropylamino-s-triazine; model 1). For comparison, ultrastructural changes in female zebra fish (Brachydanio rerio) liver were studied after exposure to 100, 1,000 and 10,000 micrograms/l atrazine for three months (exposure from egg stage to sexual maturation; model 2). Neither epithelial nor glandular cells in the gastrointestinal tract of rainbow trout reveal cytological modifications following exposure to atrazine. In contrast, hepatocytes of rainbow trout and zebra fish clearly display dose-dependent and species-specific cytopathological effects at 40 and 1000 micrograms/l, respectively. In rainbow trout (model 1), rough endoplasmic reticulum (RER) appears of particular diagnostic value for the effects of atrazine, since it already shows a full spectrum of cytological alterations after 40 micrograms/l, and since in cells without RER modifications no further cytopathological symptoms can be revealed. At 40 micrograms/l atrazine, further changes include disturbance of the intracellular compartmentation, increased heterogeneity of mitochondria (longitudinally arranged cristae, branching, size), formation of myelinated bodies as well as immigration of macrophages and granulocytes along the biliary system and the space of Disse. The separation of peripheral storage areas from the central organelle-containing cytoplasm is no longer evident at 80 micrograms/l, and the phagocytic activity of invading macrophages is drastically increased. Following exposure to 160 micrograms/l atrazine, additional pathological changes comprise clubshaped deformation of mitochondria, formation of myelinated bodies in the intermembranous space of mitochondria, increase of degranulated ER cisternae and lysosomes, as well as perisinusoidal accumulation of lipid droplets. Deformation of the nuclear envelope, elevated mitotic activity and an increased number of nuclei with two or more nucleoli indicate interactions between atrazine and the nucleus. In the liver of female zebra fish (model 2), atrazine-induced alterations are limited to increased parenchymal variability, disturbance of the intracellular compartmentation, partial RER fractionation and vesiculation, club-shaped deformation of mitochondria and an increase in the number of lysosomes, myelinated bodies and invading macrophages at 1000 micrograms/l atrazine. After three months at 10,000 micrograms/l, mortality of zebra fish is increased to 100%. According to cytopathological alterations of hepatocytes following long-term exposure, susceptibility of the test model rainbow trout to atrazine appears higher than that of the model zebra fish.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1307782 TI - [Methodologic approaches for detecting effects of environmentally relevant chemicals on fishes: exemplified by bis-(tri-n-butyltin)-oxide (TBTO)]. PMID- 1307783 TI - [Introductory address to the 2d Biotest Status Seminar]. PMID- 1307784 TI - [Effects of terbuthylazine on photo-autotrophic organisms in the aquatic ecosystem]. PMID- 1307785 TI - [Eco-toxicologic studies of the effect of boat engine emissions]. PMID- 1307786 TI - [Introductory address to the 2d Biotest Status Seminar]. PMID- 1307787 TI - [Biotest procedures for evaluation of water pollution classes according to section 19g WHG]. PMID- 1307789 TI - [New developments in the classification of substances into water pollutant classes]. PMID- 1307788 TI - [Introductory address to the 2d Biotest Status Seminar]. PMID- 1307790 TI - [Biological warning systems for the detection of pollutant incidents of the Rhine river]. PMID- 1307791 TI - [Introductory address to the 2d Biotest Status Seminar]. PMID- 1307792 TI - [Measuring emission in the Elbe river at Schnackenburg for monitoring pollution and experiences with biological warning and alarm systems at the Hamburg measuring site]. PMID- 1307793 TI - [Continuous biological test procedures for monitoring waste water and event controlled sampling techniques]. PMID- 1307794 TI - [Employment of continuous biotest systems for monitoring the Rhine river]. AB - As a part of the work of the German Commission for the Prevention of Pollution of the River Rhine biological test automats are developed and proved in a research project. The joint project "Development, Testing and Implementation of Biotests for the Monitoring of the River Rhine" sponsored by the Federal Ministry for Research and Technology (BMFT) and the Federal Environmental Agency (UBA), aims to provide a scientific and technical basis for an improved Rhine monitoring system. To realize a biological effect monitoring with functional subjects at the trophic levels of producers, primary and secondary consumers and destruents, the test spectrum includes algae, mussels, daphnia, fishes, and bacteria. Moreover, at the suborganismic level a test system with plant protoplasts is tested. Assessment schemes for the evaluation of measuring data and alarm situations, and limit values for releasing alarms are defined by the Working Group "Biotests for the Monitoring of the River Rhine" (WIR). By means of applicability criteria the most suitable biotests are chosen and recommended for the use on the River Rhine. The first results are presented in this paper. PMID- 1307795 TI - [Use of bioreactors for continuous water monitoring]. AB - A commercially available bacterial toxicity monitor ("Toxiguard", BTG Anlagentechnik, Bochum, Germany) was tested for continuous river monitoring. Operating with biofilms, this system shall detect toxic substances in the water. River water passes through two bioreactors forming a biofilm of characteristic river bacteria. The indicating parameter of the biomonitor is the respiration rate of this bacterial biofilter. The remaining oxygen content in the effluent from the biofilter is measured continuously by an oxygen electrode. This value is related to the dissolved oxygen (DO) of the river water measured in a by-pass. In presence of inhibitory substances the DO content in the biofilter increases because of the reduced respiration activity of the bacteria. The addition of nutrients may lead to an increase of biomass and of respiration activity. This results in an increasing oxygen difference between DO contents in the biofilter influent and effluent. Therefore, the degree of poisoning is better perceptible. Moreover each nutrient causes a distinct biofilm with a specific sensitivity against chemicals. This effect will be shown for Sodium-Pentachlorophenolate (Na PCP). PMID- 1307796 TI - [Detection limits of biological test procedures for assessing ecological realities]. PMID- 1307797 TI - [Bacterial electrodes with Synechoccus and Escherichia coli. A continuous test system for online monitoring of surface water]. PMID- 1307798 TI - [The FluOx measuring system: an automatic algae test instrument for continuous water monitoring]. PMID- 1307799 TI - [The protoplast biotest]. PMID- 1307800 TI - [The algae toximeter for continuous water monitoring]. PMID- 1307801 TI - [Algae toxicity tests with synchronized cultures]. PMID- 1307802 TI - [Measuring gill cover movement with the WRC (Water Research Center) fish monitor using an online system in the lower Rhine river]. PMID- 1307803 TI - [Evaluation criteria for a behavioral fish test for continuous water monitoring]. AB - Conventional fish flow through chamber tests respond only to massive injury of the animals. For this reason an indication of certain contaminants in sublethal concentrations is often impossible. The multi-parameter fish test described here aims to increase the test sensitivity in the sublethal range. The highly automated system allows to quantify and assess changes in the behaviour patterns of a small shoal of test fishes. The behavioural parameters are measured with the video-processing system "BehavioQuant". The object-related parameters swimming height, covered way, and number of turnings during the measuring cycle are recorded for each animal. As additional criteria the shoaling behaviour of the fishes is quantified and evaluated by the system. Test organisms are golden orfes Leuciscus idus melanotus. PMID- 1307804 TI - [The dynamic daphnia test: experiences from the measuring site for bodies of water]. PMID- 1307805 TI - [Basic preliminary comments on planning, implementation and evaluation of biological and eco-toxicologic test procedures]. PMID- 1307806 TI - [Emission monitoring and test systems in the High Sea estuary area. Importance of biotests for marine environmental protection]. PMID- 1307807 TI - [Detection of organic halogen compounds in tissue samples]. PMID- 1307808 TI - [Biosensors for water monitoring--status and possibilities]. PMID- 1307809 TI - [Microbial sensors for determination of biochemical oxygen consumption]. PMID- 1307810 TI - [A biotest program for risk evaluation of sediments]. PMID- 1307811 TI - [Microbial biotests with sediments]. PMID- 1307812 TI - [Experiences with biologically active tests in the study of soil pollutants]. PMID- 1307813 TI - [Phytotoxicity studies with two anionic detergents (TPBS, LAS and a herbicide (atrazine)]. PMID- 1307814 TI - [Legal requirements of biotests in the area of waste water]. PMID- 1307815 TI - [Easily eliminated substances (photo-degradation, stripping, biodegradation)]. PMID- 1307816 TI - [Biotest studies for evaluating hazardous waste water with reference to section 7a WHG]. PMID- 1307817 TI - [Biological test procedures in compliance with AbwAG and WHG]. PMID- 1307819 TI - [Evaluation of insoluble substances in aquatic toxicity tests]. PMID- 1307818 TI - [Detection of hazardous substances in waste water with reference to biodegradability and toxicity for evaluating the status of the technique exemplified by gas station and automobile repair shop waste water]. PMID- 1307820 TI - [Experience with the algae fluid waste test in North Rhine-Westphalia]. PMID- 1307822 TI - Cyst-based toxicity tests. VI: Toxkits and Fluotox tests as cost-effective tools for routine toxicity screening. AB - During the last two decades microbiotests have been developed which are independent of recruitment, maintenance and/or culturing of live stocks of test organisms. "Culture and maintenance free" microbiotests have been worked out in the Laboratory for Biological Research in Aquatic Pollution at the University of Ghent, with selected aquatic invertebrates. The new approach is based on the use of "resting stages" (cysts) as inert biological material from which live test organisms can be hatched "on demand". The "cyst-based" bioassays have recently been miniaturized in Toxkits. Four cyst-based screening tests have reached the stage of commercialization: two freshwater 24h-LC50 tests (Rotoxkit F and Streptoxkit F) and two estuarine/marine 24h-LC50 bioassays (Rotoxkit M and Artoxkit M), based on cysts of rotifer and crustacean species, respectively. Recently, the same laboratory has also been focusing on the development of a "rapid" (one hour) sublethal bioassays with aquatic invertebrates. The so called "Fluotox" screening test is based on the visual observation of in vivo inhibition of an enzymatic process, using a fluorescent substrate. Besides the advantages of rapidity and cost-effectiveness, the Fluotox assay also appears to have a remarkable predictive potential for mortality, as displayed by the remarkable correlation between the Fluotox 1h-EC50's and conventional 24h-LC50's with the same species. PMID- 1307821 TI - [A new method for cryopreservation of fish eggs and sperm samples]. PMID- 1307823 TI - [Experiences with the use of two bacterial tests in the evaluation of community and industrial waste water]. PMID- 1307824 TI - [The luminescent bacteria test for clean water legislation]. AB - Luminescent bacteria (Photobacterium phosphoreum) may be used, on the one hand, for classical toxicity tests based on the inhibition of respiration or growth and, on the other hand, their luminescence itself may become the test criterion. Such a luminescence inhibition test is commonly called a luminescent bacteria test. It may be conducted with fresh bacteria or with conserved ones. The luminescence parameter is, just like the parameter oxygen consumption, a summative parameter for undisturbed metabolic processes. Dilution series are prepared to determine the concentration level at which no inhibition of the luminous intensity is detectable in comparison with reference samples. This paper highlights the necessity of standardizing the test methods (the influence of toxic substances depends on test duration and temperature) and describes the standardized procedure established by the DIN-Arbeitskreis "Leuchtbakterientest" (Working Group of the German Institute for Standardization for the luminescent bacteria test) using freeze-dried, liquid-dried, and fresh bacteria (DIN 38,412, part 34). Results of wastewater analyses are presented and the wide range of applications is described. The choice of biotests for applications under the Federal Water Resources Management Act (Wasserhaushaltsgesetz--WHG) and the Wastewater Charges Act (Abwasserabgabengesetz--AbwAG) is discussed and the reasons for the selection of the luminescent bacteria test are explained. Within the framework of a test battery of bioassays, this test shall be used according to section 7a WHG both for evaluating the technological level of wastewater treatment and for routine monitoring of wastewater discharges. In March 1992, this test (DIN 38,412, part 34, edition March 1991) became part of the general administrative regulations for wastewater (Rahmen-Abwasser-Verwaltungsvorschrift RAV). PMID- 1307825 TI - [The physiologic background of the luminescent bacteria test]. PMID- 1307826 TI - [The luminescent bacteria test with personally cultured and freeze dried bacteria]. PMID- 1307827 TI - [Environmental monitoring with the luminescent bacteria test: the problem of false negative findings--short report]. PMID- 1307828 TI - [Examination of the water supply with the alkali and alkali-earth supplement optimized DIN luminescent bacteria test, exemplified by the Saar river]. AB - The light intensity emitted by luminescent bacteria is influenced by both the osmolarity and the ion composition of the test medium. The addition of potassium and calcium ions to a sodium chloride solution causes a considerable increase in the light intensity of bacteria. If these elements occur in the proper concentrations in the test material, the luminescence in the test sample will be higher than in the control sample containing only sodium chloride. This physiological dependence did not find the due consideration in the establishment of the German standard method for the luminescent bacteria test using Microtox bacteria (German Institute for Standardization DIN 38,412, Part 34--edition March 1991) where only the osmotic balancing by sodium chloride was taken into account. For testing chemicals, the luminescent bacteria test with Microtox reagent can be run without problems by the procedure that is recommended by Microbics Corporation and which became part of the DIN standard method. The situation is different when analyses of natural waters or effluents from wastewater plants are concerned, where matrix effects have to be expected. Stimulation of light intensity can be a reflection of a nonoptimized test medium and in the worst case may cause false negative results. The new ASW (artificial sea-water) luminescent bacteria medium according to Klein, which besides sodium contains potassium, magnesium, and calcium ions, brings stimulation to both samples and controls, effectively reducing enhancement and increasing the inhibitory effects of samples from the River Saar. However, high light stimulation rates measured in parallel tests with the DIN procedure could not be caused by the low concentrations of alkaline and alkaline-earth ions in the samples. The experiments indicate that there must be additional influencing substances which have not yet been identified. Furthermore, the experiments show that the matrix effects of unknown origin that will exert a positive influence on the light emission may be compensated by addition of alkaline and alkaline-earth ions. PMID- 1307829 TI - [Biometric procedures for the evaluation of biotests]. PMID- 1307830 TI - [Luminescence, growth and respiration as end points of the toxic effects on Photobacterium phosphoreum--short report]. PMID- 1307831 TI - [Neutral and zwitterionic detergents: dependence of biological effectiveness on critical micellar concentration]. AB - The biological activity of various zwitterionic and nonionic detergents was studied as a function of the corresponding critical micellar concentration (CMC values). The criteria chosen to measure biological activities were inhibition of bioluminescence, lysis and cell-killing of Vibrio fischeri, hemolysis, and inhibition of Daphnia magna. When Zwittergent-detergents were studied in three different bioassays their biological activity increased with decreasing CMC values. However, the biological activity of various TWEEN-detergents and alkylglucopyranosides depended on CMC-values in a very different way. We therefore conclude that CMC-values, length of alkylgroups and charge are parameters not yet sufficient to predict the potential toxicity of detergents. PMID- 1307832 TI - [Eco-toxicologic effect of detergent components evaluated in the flow test and cascade]. PMID- 1307833 TI - [Model conduit for evaluating environmental tolerance of detergent components]. PMID- 1307834 TI - [Sub-organism test procedures: applications and evaluation]. PMID- 1307835 TI - [Methodologic problems of cyto-toxicology in waste water evaluation]. PMID- 1307836 TI - [Mutagenicity as a sequela of DNA-modifying potential of water pollutants]. PMID- 1307837 TI - [Evaluating the mutagenic potential of water pollutants by measuring DNA damage using alkaline denaturation procedures]. PMID- 1307838 TI - [The DNA synthesis inhibition test for detection and quantification of the carcinogenic effects of water pollutants]. PMID- 1307839 TI - Mutatox: a genotoxicity assay using luminescent bacteria. PMID- 1307840 TI - [Use of an enzyme immunoassay for determining pesticides within the scope of the drinking water legislation]. PMID- 1307841 TI - [The role of endogenous opioids in modulation of immunosuppression in fish]. AB - We have previously shown that social confrontation between aggressive fish (e.g., Tilapia) produces a suppression of several immunological parameters--nonspecific cytotoxicity and mitogen-stimulated proliferation in pronephric lymphocytes--in the subordinate fish. By using the opioid antagonist, naltrexone, we now demonstrate indirectly that this immunosuppression is in part mediated by the endogenous opioid system. Evidence is presented that naltrexone-mediated reversal of immunosuppression may be limited to the populations of the cytotoxic and T cell lineages. The proliferative response to lipopolysaccharide is unaffected by naltrexone. Our data also demonstrate that serum from subordinate (immunosuppressed) fish is immunosuppressive in normal fish: an effect that can be reversed by naltrexone. These results support a link between the neuroendocrine and immune systems in these animals. PMID- 1307842 TI - [Measuring enzymatic activities in vivo as an aid in water monitoring]. PMID- 1307843 TI - [Cholinesterase inhibitor test--report on the ring test]. PMID- 1307844 TI - [Enzymatic procedures for detection of biotransformation (detoxication activity) of the fish liver--a contribution to monitoring biological effects]. PMID- 1307845 TI - [Joint monitoring of the North Sea (North Sea Task Force, NSTF). MFO studies as a portion of the German contribution to the Quality Status Report (QSR)]. PMID- 1307846 TI - [Metallothioneins as long-term indicators of surface water pollution by heavy metals]. PMID- 1307847 TI - [Hazardous substances--quality goals in protection of surface water (Federal/Regional Working Group for Quality Goals)]. PMID- 1307848 TI - [NOEC values of the 21 d-Daphnia test in comparison with the acute Daphnia test and with Scenedesmus cell division inhibition test]. PMID- 1307849 TI - Fractionation factors for late effects in head and neck cancers. PMID- 1307850 TI - The British Columbia Mammography Screening Program: evaluation of the first 15 months. AB - We report our experiences in the first 15 months of a government-funded pilot project begun in 1988 to study the feasibility of rapid throughput, low-cost screening mammography in British Columbia. The primary goals of the project were (1) to determine the unit cost of screening mammography within the context of the program; (2) to design and put into operation a centralized system of data collection, analysis, and quality control to enable calculations of cancer detection rates, biopsy rates, biopsy yield ratios, staging, and other specific cancer characteristics; and (3) to study compliance in the community where the program was offered. A total of 11,824 women had mammography at a unit cost of U.S. $32.66. Computerized analysis revealed that (1) 11% of women had known primary risk factors; (2) findings on mammograms were interpreted as abnormal in 9% of screening examinations; (3) breast cancers were confirmed in 47 (22%) of 211 patients who had biopsies, and 87% of these were stage 0-1. The overall cancer detection rate was four per 1000, with five per 1000 for women who had not had mammography in the preceding 2 years and one per 1000 for women who had had mammography in the past 2 years. The results show that screening mammography can be conducted at low cost. Data collection and analysis and compliance were sufficiently convincing to initiate province-wide expansion. PMID- 1307851 TI - Learning medicine. Too many books, too few journals. PMID- 1307852 TI - Cranio-orbito-zygomatic measurements from standard CT scans in unoperated Crouzon and Apert infants: comparison with normal controls. AB - Cranio-orbito-zygomatic measurements taken from standard axial computed tomographic (CT) scans of unoperated patients with Crouzon syndrome (6 males, 14 females) and Apert syndrome (6 males, 10 females) under 1 year of age were compared to each other and to normal controls (40 males, 35 females). Fifteen cranio-orbito-zygomatic variables were measured and repeated. Means and standard deviations were computed for each sex, and means were pooled since they were not significantly different. Correlation coefficients for repeat measures (intra observer error) of each variable showed good reproducibility. Only the lateral orbital wall angle differed between the syndromes (p = .034), suggesting that upper facial differences (as measured by these variables) do not manifest themselves at this young age. All measurements for both syndromes, except one, were outside the 95 percent confidence range for age-matched controls. Measurements taken from standard CT scans provide an objective comparison between specific syndromes and the normal population. PMID- 1307853 TI - Spontaneous resolution of peliosis of the liver and spleen in a patient with HIV infection. PMID- 1307854 TI - Randomized trials: what's the problem? PMID- 1307855 TI - Arterial hypertension and neurovascular compression at the ventrolateral medulla. A comparative microanatomical and pathological study. AB - Intraoperative observations and animal experiments suggest that neurovascular compression at the left ventrolateral medulla is a possible etiological factor in essential hypertension. In pursuing this hypothesis, the authors examined the neurovascular relations in the posterior cranial fossa of 24 patients with essential hypertension, of 10 with renal hypertension, and of 21 normotensive control patients. Artificial perfusion of the vessels and microsurgical investigations during autopsy identified the vascular relations at the brain stem and at the root entry zone of the caudal cranial nerves. There was no evidence of neurovascular compression at the ventrolateral medulla on the left side in any patient from the control group or among those with renal hypertension. Two normotensive patients had neurovascular compression at the right ventrolateral medulla by the posterior inferior cerebellar artery. In contrast, all patients with essential hypertension had definite neurovascular compression at the left ventrolateral medulla. Additional compression of the right side was seen in three of these patients. Based on the anatomical appearance, it was possible to define three distinct types of neurovascular compression at the ventrolateral medulla. Common to all three types is the compression of the medulla oblongata at its rostral part just caudal to the pontomedullary junction and lateral to the olive in the retro-olivary sulcus. Comparative histopathological study of the microsurgically examined brain-stem specimens revealed no differences between patients with essential hypertension, those with renal hypertension, and normal controls. There was a structural integrity at the site of neurovascular compression at the ventrolateral medulla. The microanatomical findings of this study show that neurovascular relations at the ventrolateral medulla in essential hypertension give rise to pulsatile compression on the left. This supports Jannetta's hypothesis of neurovascular compression at the left ventrolateral medulla as an etiology of essential hypertension. PMID- 1307856 TI - Availability of medicines. PMID- 1307857 TI - An algorithm for ordering pretreatment orthodontic radiographs. AB - A study was conducted to identify selection criteria for ordering pretreatment orthodontic radiographs. Thirty-nine orthodontists evaluated six test cases. They provided information on the rationale for ordering each specific radiograph and the impact of the radiograph on the diagnosis and treatment plan. Skeletal relationship of the jaws was the most common indication for a radiograph request, followed by root formation/length and molar position or development. Of the radiographs, 16% produced a change in diagnosis, and 20% produced a change in treatment plans. The criteria specified for the radiographs, their impact, and relevant information in the literature were used to develop an algorithm or set of decision rules that, when tested on the six test cases, resulted in a 36% reduction in the total number of radiographs. PMID- 1307858 TI - Low-cost screening mammography. PMID- 1307859 TI - Percutaneous endoscopic gastrostomy feeding. PMID- 1307860 TI - The Oregon Health Plan: to cover all diagnostic visits. PMID- 1307861 TI - Why does Australia have no national drug policy? PMID- 1307862 TI - On pulmonary manifestations of HIV infection in children. PMID- 1307863 TI - Randomized trial: another opinion. PMID- 1307864 TI - Solution studies of the interactions between the histone core proteins and DNA using fluorescence spectroscopy. AB - The equilibrium interactions between histone H2A-H2B and H3/H4 subunits with 200 base pair chicken erythrocyte DNA have been studied by monitoring the fluorescence polarization of a long-lived fluorescence probe covalently bound to the histone subunits. These studies have brought to light the formation of highly asymmetric complexes exhibiting very high histone/DNA stoichiometries as well as very high apparent affinities. The stoichiometries observed for these non nucleosome complexes depended both upon the concentration of the histones and the concentration of the DNA 200mer. The observed stoichiometries varied approximately between 4 and 16 histone octamers/DNA 200mer and the affinities were in the nanomolar range. These results are discussed in terms of their in vitro as well as their possible in vivo significance. PMID- 1307865 TI - Horseshoe lung: an additional component of the Vater association. PMID- 1307866 TI - Examination of Koch's postulates for Borrelia burgdorferi as the causative agent of limb/joint dysfunction in dogs with borreliosis. AB - Borrelia burgdorferi has been implicated as the causative agent of borreliosis in dogs, which is characteristically a limb/joint disorder, but can be associated with multiple-organ dysfunction. Attempts to reproduce this disease by inoculating dogs with B burgdorferi have not been successful. In the study of this report, B burgdorferi from Ixodes dammini ticks was used to induce signs of limb/joint dysfunction, fever, anorexia, depression, and systemic infection in dogs. A pure culture of this bacterium from the blood of an infected dog has been used to fulfill Koch's postulates for B burgdorferi as the causative agent of limb/joint dysfunction associated with borreliosis in dogs. PMID- 1307867 TI - Early parenteral penicillin in meningococcal disease. PMID- 1307868 TI - AIDS--beyond education. PMID- 1307869 TI - Propofol and ECT. PMID- 1307870 TI - Cocaine abuse: an expanding healthcare problem for the 1990s. AB - Cocaine, the most addictive recreational drug available, has increased in popularity and widespread use in the past decade. Crack, a new form of cocaine that is smoked, is purer and more rapidly absorbed into the vascular system, greatly increasing the risk of overdose. Cocaine produces many physiologic effects on the body systems. This case report focuses on two cardiovascular responses related to cocaine use: cardiomyopathy and coronary vasospasm. Cocaine abusers may present with complaints of chest pain or other nonspecific symptoms that require diligent assessment skills to be recognized as cocaine-related. Therefore, it is essential that nurses be knowledgeable about the effects of cocaine and the symptoms of cocaine abuse. PMID- 1307871 TI - Patients' perceptions of pulmonary problems and nursing interventions during hospitalization for Pneumocystis carinii pneumonia. AB - BACKGROUND AND METHODS: The descriptive, correlational study examined patients' perceptions of pulmonary problems and nursing interventions in a sample (n = 201) of persons living with AIDS hospitalized for Pneumocystis carinii. Additionally, the study assessed differences in physiological variables, patient symptoms, and functional status based on the type of problems identified: dyspnea, pulmonary problems without dyspnea, and nonpulmonary problems. RESULTS: A total of 601 problems was identified including 61 instances of dyspnea and 83 reports of other pulmonary problems. The remainder of the problems was nonpulmonary. Nursing interventions associated with dyspnea and pulmonary problems other than dyspnea were mainly broadly defined interventions such as oxygen and medication administration. When patients were placed into three groups based on identification of dyspnea, pulmonary problems without dyspnea, or only nonpulmonary problems, there were no differences between groups in functional status or patient symptoms of pain, nausea, or fatigue as measured by the Quality Audit Marker. CONCLUSIONS: This study demonstrated that hospitalized patients with Pneumocystis carinii present with a broad array of problems. Contrary to expectations, dyspnea was not ubiquitous but was reported by less than one-third of this sample. When dyspnea was present there were few independent nursing interventions that patients identified. Studies are needed to test effective strategies for the nursing management of dyspnea and a large variety of other patient problems associated with HIV infection. PMID- 1307872 TI - Making patient self determination a reality in critical care. PMID- 1307873 TI - A silent epidemic: coronary disease in women. PMID- 1307874 TI - New directions. PMID- 1307875 TI - New nurses, new spaces: a preview of the AACN History Study. AB - This article previews selected findings of the American Association of Critical Care Nurses History Project that is being conducted under the auspices of the Center for the Study of the History of Nursing at the University of Pennsylvania. Using methods of social history research, we reviewed pertinent literature, studied documents of institutions and organizations, and interviewed a broad array of participants. Analysis of this evidence resulted in a history of the evolution of nursing and hospital care for patients with life-threatening illnesses during the 40-year period since 1950. We explored the effects of changing public and professional ideas about the nature of critical illness, the effects of technology, and the historical dimensions of critical care nursing. Special attention was given to the events and circumstances that led to the development of AACN and the reciprocal relationships between AACN and the care of critically ill people. PMID- 1307876 TI - Nurse/physician collaboration: solving the nursing shortage crisis. AB - This summary article discusses the status of the nursing shortage in the United States, with emphasis on successful strategies to address it. Liaisons between the American Association of Critical-Care Nurses (AACN) and the Society for Critical Care Medicine, as well as with the American College of Cardiology, are highlighted, with primary emphasis on the strategy of nurse-physician collaboration. PMID- 1307877 TI - Future of critical care. AB - Critical care, as a specialty in both nursing and medicine, is well recognized and the number of people requiring hospitalization for critical illnesses continues to increase. The purpose of this paper is to examine the future and the changes that lie ahead in critical care. New and expanding roles for nurses are projected along with a continued refinement and expansion of the critical care medicine subspecialty for physicians. A variety of changes in critical care are anticipated that reflect our increasing abilities in biotechnology, basic and clinical research, and data management. These changes are viewed for their obvious impact on cost, ethical controversies, and patient care and outcome. PMID- 1307878 TI - Monitoring and management of acute circulatory problems: the expanded role of the physiologically oriented critical care nurse. AB - The intensive care unit is set apart from other hospital patient care areas by (1) physiological instrumentation that permits better assessment and more effective therapy and (2) more intensive nursing. These capabilities allow nurse and physician intensivists to evaluate tissue perfusion and tissue oxygenation by the temporal patterns of oxygen delivery and oxygen consumption, as well as hemodynamics. Such evaluation provides important insight into the functional impairment of hemorrhagic, traumatic, septic, and postoperative shock. Using artificial intelligence-based systems, complex clinical algorithms--tailored to specific patient conditions--have been developed and are described. These algorithms are based on both invasive and noninvasive monitoring systems and on clinical experience with a large series of high-risk surgical patients. PMID- 1307879 TI - Superior vena cava syndrome: etiology, diagnosis, and treatment. AB - Superior vena cava (SVC) syndrome is a critical condition in which an intrathoracic mass lesion compresses the SVC and promotes the development of head and upper body edema and cyanosis. SVC syndrome develops in 10% of patients with a right-sided malignant intrathoracic mass lesion. Diagnostic evaluation and emergency therapy are always necessary to assess and alleviate airway obstruction, cerebral venous hypertension and symptoms secondary to mediastinal compression. Radiation therapy and venous bypass of the obstructed SVC are both used successfully as early treatment. Although radiation therapy to the malignant process may provide initial decompression, a more sustained decrease in venous pressure occurs in patients who also undergo decompressive SVC surgical bypass. SVC bypass should be considered early in the course of patients with profound cerebral or laryngeal edema, patients with extensive thrombosis of the SVC, and in rare patients afflicted with severe venous hypertension and in whom a tissue diagnosis requires a mediastinal exploration. PMID- 1307880 TI - Clinical comparison of two- and three-wavelength systems for continuous measurement of venous oxygen saturation. AB - OBJECTIVE: To evaluate clinically the accuracy of continuous SvO2 systems to reflect reference SvO2 values over a 24-hour period. DESIGN: Randomized clinical trial. SETTING: Six-bed cardiac surgical intensive care unit of a 540-bed federal facility. POPULATION: Sixty postoperative cardiac patients. INTERVENTIONS: Random assignment to a two- or three-wavelength continuous SvO2 catheter for postoperative SvO2 monitoring. At 4-hour intervals over a 24-hour period, mixed venous blood samples were analyzed with a reference cooximeter and compared with the monitor value of the SvO2 catheter. MAIN OUTCOME MEASURES: A reference cooximeter method to measure SvO2 in mixed venous blood; SvO2 as measured by the in-line, SvO2 catheter system. RESULTS: SvO2 measured by the three-wavelength system did not differ significantly from the reference SvO2 measurement. In contrast, SvO2 measured by the two-wavelength system was significantly lower than the reference SvO2 measurement within 4 hours of admission to the critical care unit and remained significantly lower throughout the 24-hour study period. CONCLUSIONS: The results of this clinical study confirmed a previous study in dogs, showing that SvO2 is measured more accurately by the three-wavelength continuous monitoring system. PMID- 1307881 TI - Room-temperature thermodilution cardiac output: central venous vs right ventricular port. AB - OBJECTIVE: To assess the accuracy of room-temperature thermodilution cardiac output measurements from the right ventricular port. In addition, waveform patterns were evaluated to determine the actual location of the right ventricular port. DESIGN: Central venous port cardiac output measurements were compared with right ventricular port cardiac output measurements using the same right-heart catheter. SETTING: The general intensive care unit of Memorial Sloan-Kettering Cancer Center. PATIENTS: Thirty-seven critically ill cancer patients with 38 different right-heart catheters were evaluated. INTERVENTION: Four injections of 10 mL normal saline at room temperature were made through each port; the results of the last three injections were averaged. Cardiac output determinations from both ports were completed in less than 10 minutes. The order of port injection was random. RESULTS: No difference was noted between cardiac output determinations from the two ports in a paired t test. Of 38 right-heart catheters, 17 were in the right ventricle and the other 21 in the right atrium. A comparison of ports in the 17 right ventricle catheters showed no difference with a significant (P < .01; R2 = 0.96) correlation. CONCLUSION: Thermodilution cardiac output measurements using 10 mL normal saline at room temperature can be determined accurately using the right ventricular port if the central venous port becomes nonfunctional. PMID- 1307882 TI - Evaluation of a system for intragastric pH monitoring of intensive care unit patients: preliminary report. AB - BACKGROUND: A new pH probe-tipped nasogastric sump tube is available to monitor gastric pH conveniently. This study assesses its ability to measure gastric acidity accurately. METHODS: The accuracy of the combined pH probe nasogastric tube (GrapHprobe ST) was determined by comparing it with standard buffer solutions (pH 1.0, 2.0, 4.0 and 7.0) traceable to the National Institute of Standards and Technology. Gastric pH values obtained were compared with values obtained using indicator paper and a calibrated glass electrode on gastric aspirate. RESULTS: Although statistically significant differences were found in vitro between the pH of three of the buffer solutions and the pH values obtained by the nasogastric sump tube, the results were within 0.5 pH unit. When rounded to the nearest pH unit, all values were the same as the buffer solutions. No significant difference was found in the pH values obtained during in vivo testing. CONCLUSIONS: The GrapHprobe ST measured gastric pH within reasonable accuracy in this small series. PMID- 1307883 TI - Minimizing diagnostic blood loss in critically ill patients. AB - BACKGROUND: Blood loss from diagnostic procedures in critically ill patients needs to be minimized. Traditionally, when drawing blood from arterial lines, the initial sample used to clear the line has been discarded (open method). Use of a temporary reservoir enables this discard sample to be returned to the patient (closed method). METHODS: Critically ill surgical patients were prospectively randomized to the open or closed method of drawing blood from arterial lines. Blood loss to diagnostic sampling was measured in both groups. RESULTS: A comparison study (n = 1657) of these two methods revealed that blood loss to the patient was significantly decreased (P << .01) using the closed method. Mean blood loss per patient per day was 69 mL in the open group (n = 873) vs 35 mL in the closed group (n = 784). CONCLUSIONS: Use of the closed method when drawing blood from arterial lines results in a significant decrease in blood lost to diagnostic procedures. PMID- 1307884 TI - The effects of ocean sounds on sleep after coronary artery bypass graft surgery. AB - OBJECTIVE: To investigate the influence of ocean sounds (white noise) on the night sleep pattern of postoperative coronary artery bypass graft (CABG) patients after transfer from an intensive care unit. DESIGN: A before and after trial with an experimental and a control group was used in this intervention study. SETTING: A large public hospital with primary, secondary, and tertiary care facilities. PATIENTS: A consecutive sample of 60 first-time CABG patients was systematically assigned to the experimental or the control group. INTERVENTION: For the experimental group, the sounds were played on the Marsona Sound Conditioner (Marpac Corporation, Wilmington, NC) for three consecutive nights posttransfer from the ICU. No control of environment, except for the elimination of white noise, was done for the control group. MAIN OUTCOME MEASURES: The Richards Campbell Sleep Questionnaire, a visual analog scale, provided self-reported sleep scores on six variables. Analysis of covariance was used to test the difference between the posttest scores of the groups, with the pretest used as the covariate. RESULTS: There were significant differences in sleep depth, awakening, return to sleep, quality of sleep, and total sleep scores; the group receiving ocean sounds reported higher scores, indicating better sleep. There was no difference in the falling asleep scores. CONCLUSION: The use of ocean sounds is a viable intervention to foster optimal sleep patterns in postoperative CABG patients after transfer from the ICU. PMID- 1307885 TI - Cardiopulmonary support in the intensive care unit. AB - The cardiopulmonary support system is an extracorporeal device that allows for rapid cardiopulmonary support of the critically ill patient in the intensive care unit. It provides immediate and complete support of cardiac and pulmonary functions to maintain perfusion to vital organs in patients who are severely physiologically compromised (eg, in cardiogenic shock, adult respiratory distress syndrome or pulmonary edema). Successful cardiopulmonary support requires systemic anticoagulation, percutaneous venous and arterial cannulation and careful monitoring by the critical care team to maintain adequate tissue perfusion and oxygenation. Although patient mortality can occur secondary to bleeding, embolism or sepsis, this technique provides life-sustaining circulatory and respiratory support until definitive treatment can be initiated. PMID- 1307886 TI - Cardiac transplantation: update. PMID- 1307887 TI - Sodium nitroprusside-induced cyanide intoxication and prevention with sodium thiosulfate prophylaxis. AB - Sodium nitroprusside is an antihypertensive agent used frequently in the critical care setting. Recently, the Food and Drug Administration (FDA) published a report that led to a labeling change emphasizing the pharmacokinetics of nitroprusside with metabolism to highly toxic cyanide. Although evidence validates that cyanogenesis occurs with nitroprusside administration, prevention and treatment of cyanide poisoning is rarely instituted in clinical practice. Simultaneous infusion of thiosulfate with nitroprusside provides the sulfur donor necessary to prevent cyanide accumulation. Cyanide combines with thiosulfate to form the less toxic sodium thiocyanate, which is then excreted. A 10:1 ratio of nitroprusside to thiosulfate in the infusion eliminates the possibility of cyanide intoxication without altering the efficacy of nitroprusside. PMID- 1307888 TI - Coronary artery bypass graft surgery in older women and men. AB - OBJECTIVE: To compare women and men younger than 70 years of age and 70 years or older undergoing coronary artery bypass surgery. DESIGN: Retrospective chart review, case-control series. SETTING: University medical center. PATIENTS: All women (n = 465) having first-time isolated coronary artery bypass surgery between 1983 and 1988, and 465 men matched for age and year of surgery. Predominantly white; 33% were 70 years or older. MEASURES: Medical record data: demographics, preoperative comorbidities, perioperative and postoperative complications, mortality, length of stay. RESULTS: Preoperatively, women 70 years of age or older had a higher incidence of congestive heart failure, renal disease and hypertension, and a lower incidence of smoking history compared with women less than 70 years old. Men 70 years or older had a higher incidence of congestive heart failure and renal disease, and a lower incidence of smoking history compared with men less than 70 years old. There was no difference in mortality between older and younger women, whereas the mortality rate for older men was higher than that for younger men. There were fewer differences between women younger than 70 and those 70 years or older in incidence of postoperative complications than between men of those same age groups. Among patients 70 years or older, incidence of postoperative congestive heart failure was greater in women than in men. There were no other differences between women and men younger than 70 and those 70 years or older in incidence of postoperative complications. Controlling for the influence of postoperative complications, age was related to length of stay for women and men. CONCLUSIONS: Older women were at no greater risk of mortality or the occurrence of postoperative complications compared with younger women or older men. A functional component influencing recovery and length of hospital stay needs to be considered to provide optimal nursing care after surgery. PMID- 1307889 TI - Spouse adaptation to mate's CABG surgery: 1-year follow-up. AB - OBJECTIVE: The purpose of this study was to describe spouses' life stressors, supports, perceptions of illness severity, role strain, physical and mental symptoms of stress, and marital quality 1 year after the mate's coronary artery bypass graft surgery. METHODS: This descriptive study was the third component of a longitudinal panel investigation. (The first component was a period within 48 hours of surgery, and the second was 6 weeks after discharge.) One year after the mate's surgery, spouses received the following instruments in the mail: the Family Inventory of Life Events and Changes, the Norbeck Social Support Questionnaire, the Cantril Ladder Scale, the Strain Questionnaire, the Role Strain Scale and the Dyadic Adjustment Scale. Subjects were a convenience sample of 49 women whose husbands were alive 1 year after their first bypass surgery. Of the women in the sample (n = 49), 98% were white, and the mean age was 56 years. RESULTS: Social support was moderate and significantly less 1 year after surgery than during the first two components (48 hours and 6 weeks after surgery). Women still perceived their husbands to have some illness severity 1 year after surgery. They continued to have physical and mental symptoms of stress and had significantly greater role strain than during the first two periods. Marital quality was average. Spouses reported making several life-style changes. DISCUSSION: During the first year after the patient's bypass surgery, spouses experienced many changes. Although physical and mental symptoms of stress remained the same, role strain increased and social support decreased. The findings suggest testing of such interventions as stress management and time management techniques, support groups, and other psychoeducational interventions. CONCLUSIONS: Although the situation remains difficult for the spouse 1 year after the patient's surgery, nurses and physicians can foster and support spouses through many adjustments and changes. PMID- 1307890 TI - Urinary bladder/pulmonary artery temperature ratio of less than 1 and shivering in cardiac surgical patients. AB - BACKGROUND: Temperature gradients that normally exist between body areas may be altered as a result of heat generated by shivering. METHODS AND POPULATION: Two core thermal gradients between pulmonary artery and urinary bladder were compared with shivering in 37 coronary artery bypass graft patients. Pulmonary artery and urinary temperature were measured every 15 minutes, and shivering was evaluated electromyographically. RESULTS: Shivering developed in 28 patients (76%). With shivering the pulmonary artery/urinary bladder temperature ratio was less than 1 but in the nonshivering group was greater than 1. Correlation (r value) between pulmonary artery and urinary temperature ranged from 0.93 to 0.99. Rate pressure product was higher in the shivering group than in the nonshivering group. A pulmonary artery/urinary bladder temperature ratio of less than 1 was seen with shivering in this subset of patients. CONCLUSION: Pulmonary artery and urinary bladder temperatures are readily available clinically. The combination of a ratio of less than 1 and an increase in rate pressure product should be considered suggestive of shivering in coronary artery bypass graft patients. PMID- 1307891 TI - Gastric intramucosal pH: a noninvasive method for the indirect measurement of tissue oxygenation. AB - BACKGROUND: Monitoring the adequacy of tissue oxygenation is an important goal in the care of the critically ill patient. Global alterations in tissue oxygenation are inferred from changes in systemic oxygen transport (defined as the product of cardiac output and arterial oxygen content) and total oxygen consumption. These parameters, however, cannot measure the level of oxygenation of specific tissue beds, in particular those that are first affected by hypoxia, such as the gastrointestinal tract and the kidneys. DISCUSSION: Gastrointestinal tonometry is a new method for measuring the partial pressure of carbon dioxide of the gastrointestinal mucosa. This information can be used in conjunction with the arterial blood bicarbonate to calculate the pH of the mucosa. Mucosal acidosis correlates well with the onset of anaerobic metabolism in response to hypoxia or sepsis. This review discusses the basic principles of tonometry, the results of experimental and clinical studies, and the practical aspects related to the implementation and use of tonometers in patients in the critical care unit. CONCLUSION: Gastrointestinal tonometry is a relatively noninvasive device that appears capable of measuring metabolic changes produced by hypoxia. Because of the sensitive nature of the gastrointestinal mucosa, these changes often occur well in advance of other, more common, indices of hypoxia. The use of the tonometer may become a routine procedure in the overall monitoring of critically ill patients. PMID- 1307892 TI - Pulmonary artery pressure measurement in patients with elevated pressures: effect of backrest elevation and method of measurement. AB - OBJECTIVE: To determine whether pulmonary artery pressure measurement is accurate if the head of the bed is elevated; to compare the end-expiratory graphic recording and digital monitor methods for pulmonary artery pressure measurement; to determine whether either mean arterial pressure or mixed venous oxygen saturation changes during backrest elevation. DESIGN: Nonrandomized clinical trial. SETTING: A six-bed cardiac surgical intensive care unit of a 540-bed federal facility. POPULATION: Twenty-five postoperative cardiac surgical patients with elevated pulmonary artery pressures (systolic higher than 35 mm Hg). INTERVENTIONS: In supine patients pulmonary artery pressures were measured at each of the following backrest elevations: 0, 20, 30, 45 and again at 0 degrees. Measurements were obtained once during mechanical ventilation and once during normal breathing after extubation. MAIN OUTCOME MEASURES: End-expiratory graphic recording of pulmonary artery pressures; digital monitor values of pulmonary artery pressures; mean arterial pressure; and mixed venous oxygen saturation. RESULTS: No statistical difference was found in pulmonary artery pressures measured at each of the backrest elevations during mechanical ventilation or normal breathing after extubation. Pulmonary artery diastolic and pulmonary capillary wedge pressures obtained with the digital monitor method were significantly lower than the end expiratory graphic recording method during normal breathing after extubation but not during mechanical ventilation. No changes in mean arterial pressure or mixed venous oxygen saturation occurred during backrest elevation. CONCLUSIONS: These results show that pulmonary artery pressures can be measured accurately with the head of the bed in an elevated position. The data indicate that obtaining pulmonary artery pressure measurements from the digital display of the bedside monitor is accurate when respiratory wave form fluctuations are minimal but may lead to inaccurate values with prominent respiratory fluctuations. Further research is needed to validate this finding in different patient populations and with other models of monitoring equipment. PMID- 1307893 TI - Effectiveness of nursing involvement in bedside monitoring and control of coagulation status after cardiac surgery. AB - OBJECTIVE: This study explores: (1) the feasibility of involvement of nursing staff in routine bedside testing of activated clotting time and (2) joint implementation with resident medical staff of a preformulated plan for management of mediastinal bleeding after cardiac surgery. DESIGN: Patients were divided randomly into two groups, an experimental group (n = 108) subjected to ACT testing and management by protocol, and a control group (n = 146) treated by independent medical decisions. RESULTS: Bleeding, volume of blood replaced, abnormal coagulation profiles and reoperations to control bleeding and its consequences were all reduced in the study group. CONCLUSION: We concluded that bedside measurement of activated clotting time by nursing staff, associated with therapy based on a flow diagram, enhanced the overall management of early mediastinal bleeding after cardiac surgery as compared with independent management decisions by resident medical staff. In addition, the method provided a sensitive and reliable means of detecting and correcting rebound heparinization in the early postoperative period. PMID- 1307894 TI - Parental coping and activities during pediatric critical care. AB - OBJECTIVE: To investigate the relationship of locus of control, parental age, and state anxiety to parental coping and activities performed during hospitalization of a child in a pediatric critical care center. DESIGN: Cross-sectional. SETTING: Pediatric critical care center at a university medical center. PARTICIPANTS: A convenience sample of 47 parents of 47 children hospitalized in a critical care center. MAIN OUTCOME MEASURES: Parental coping strategies and activities performed during hospitalization in a critical care center. RESULTS: Older, more self-directed and less anxious parents were found to use coping strategies focusing on problem solving rather than on their emotional response to a child's hospitalization. Further, those who used the problem-focused coping modes were more likely to be involved in caring for the child, while parents who used emotion-focused coping modes participated less in care activities. CONCLUSIONS: Appropriate strategies to bolster coping and reduce stress of parents need to be constantly reassessed because coping mechanisms vary according to parental age, locus of control, anxiety level, and parental involvement in child-care activities. More research is needed in the changes of parental coping mechanisms with time and child-care activity, to assess the benefits of interventions planned to encourage a problem-focused approach. PMID- 1307895 TI - Job stress and burnout in acute and nonacute pediatric nurses. AB - OBJECTIVE: To identify predictors of burnout in pediatric nurses and to compare the incidence of burnout, job stress, anxiety and perceived social support in acute and nonacute care pediatric nurses. DESIGN: Prospective correlational descriptive methodology was used to predict high, moderate or low burnout from length of work experience, perceived work stress and social support and anxiety. SUBJECTS AND SETTING: Registered nurses (n = 121) employed full-time in neonatal and pediatric intensive care units and pediatric intermediate care units. MEASUREMENTS AND RESULTS: Measures of job stress, anxiety, experience, social support and burnout were compared in acute and nonacute care pediatric nurses. The overall mean incidence of burnout was in a moderate range for both acute and nonacute care pediatric nurses for the emotional exhaustion and depersonalization subscales and in the high range of personal accomplishment subscales of the Maslach Burnout Inventory. Analysis of variance revealed no differences between groups. However, when nurses were grouped by high, moderate and low burnout scores, chi-square analysis revealed significant differences. More acute care nurses reported high burnout and more nonacute care nurses reported low burnout. Discriminant function analysis revealed that job stress was the strongest significant predictor of burnout, followed by state anxiety, coworker support, trait anxiety and experience on the unit. CONCLUSIONS: Even though high burnout levels are more frequent in acute care pediatric nurses, burnout is a problem in both acute and nonacute care pediatric nurses. The pattern of results suggests that efforts directed toward reducing anxiety and job stress and increasing coworker support, particularly for less experienced nurses, might reduce burnout. PMID- 1307896 TI - Survey of the degree to which critical care nurses are performing current procedural terminology-coded services. AB - PURPOSE: To identify the degree to which current procedural terminology-coded services are provided by critical care nurses. Current procedural terminology codes are used by government and private insurers for reimbursement for office, home, hospital, nursing home and emergency department services. METHOD: Out of 100 randomly selected registered nurses invited to participate in this national survey, 43 completed the survey questionnaire. The majority of respondents were 18 to 40 years old, had a bachelor's degree, had practiced nursing between 5 and 10 years, and were employed as staff or charge nurses in an intensive care or emergency room setting. RESULTS: More than 70% of the group were found to perform 28 codes. The codes performed by the greatest number (42) were blood or blood component transfusion and cardiopulmonary resuscitation. One-way analysis of variance applied to the amount of supervision the nurses received while performing the codes and the educational level of the nurses revealed a significant difference between the groups. Post hoc analysis of all possible group comparisons showed that diploma-prepared nurses reported significantly more supervision than nurses having a bachelor's or master's degree. CONCLUSION: This exploratory study indicates that critical care nurses frequently perform selected codes with little or no supervision by a physician. PMID- 1307897 TI - Computerized clinical simulations: a strategy for staff development in critical care. AB - BACKGROUND: Identifying the learning needs of employees and evaluating the results of staff development offerings are essential elements of the responsibilities of the staff development educator. High patient acuity, the shortage of critical care nurses, and rapidly changing technology within the critical care environment demand the provision of staff development offerings that are appropriate for the learning needs of critical care nurses and the evaluation of the effect of programs on critical care nursing practice. OBJECTIVE: The purposes of this descriptive, correlational study were to compare the ability of a knowledge test, a self-evaluation tool, and computerized clinical simulations to discriminate between nurses with varied levels of knowledge and experience, and to compare the learning needs identified from the three types of evaluative instruments. METHODS: Each subject (n = 142) completed the Basic Knowledge Assessment Tool for Critical Care, Cardiovascular Self Evaluation Tool, and four computerized clinical simulations. RESULTS: Both the Basic Knowledge Assessment Tool and the Cardiovascular Self-Evaluation Tool discriminated between experienced/inexperienced and Advanced Cardiac Life Support certified/noncertified critical care nurses. The computerized clinical simulations discriminated according to Advanced Cardiac Life Support certification, but not between experienced and inexperienced critical care nurses. The computerized clinical simulations identified more specific learning needs than did the Basic Knowledge Assessment Tool or Cardiovascular Self Evaluation Tool. CONCLUSIONS: The evidence for discriminant validity, adequate internal consistency reliability, and ease of administration supports the continued use of these two tools as methods for critical care staff development needs assessment and evaluation. In addition, the study findings support the use of computerized clinical simulations as an adjunct to other needs assessment and evaluation methods in nursing staff development. PMID- 1307898 TI - Fluctuation in mixed venous oxygen saturation in critically ill medical patients: a pilot study. AB - OBJECTIVE: To determine fluctuation in mixed venous oxygen saturation in critically ill medical patients during a period of rest. DESIGN: Nonexperimental, descriptive. SETTING: The medical and coronary intensive care units in a large county hospital in south-central Texas. PATIENTS: Twenty critically ill patients, aged 19 to 85, who had placement of a pulmonary artery catheter capable of continuous monitoring of mixed venous oxygen saturation. The majority had a diagnosis of respiratory failure and required mechanical ventilation. METHODS: Mixed venous oxygen saturation was recorded each minute for a 2-hour period in either early morning or late afternoon hours. Minute-by-minute values obtained during a 30-minute period of rest were used to determine fluctuation. The lowest and highest mixed venous oxygen saturation values during the period were used to calculate percent changes from average values (fluctuation). RESULTS: The range of fluctuation was +/- 6% of the average mixed venous oxygen saturation value for 80% of the sample. Four patients had a greater range of fluctuation: however, their actual mixed venous oxygen saturation values were within a clinically acceptable range. No significant differences in percentage of low or high fluctuation were noted for the following variables: time of day, medication administration, oxygen delivery, oxygen consumption and average mixed venous oxygen saturation. The percentage of low fluctuation was significantly lower for four patients who were not mechanically ventilated. CONCLUSIONS: Knowledge of normal fluctuation enables the care giver to evaluate changes in mixed venous oxygen saturation in response to activities and/or treatments. Additional study of fluctuation in homogenous groups of critically ill patients is warranted. PMID- 1307899 TI - Management of ventricular arrhythmias: then and now. AB - OBJECTIVE: To review the changing environment of antiarrhythmic therapy. DATA SOURCES: The majority of articles chosen were written by experts in the field of arrhythmia management. The references include a pilot study, abstracts, original articles and results of study groups. An equal number of sources used in this article were obtained from fellow healthcare professionals and MEDLINE searches. STUDY SELECTION: Large, controlled clinical trials in which patient populations had structural heart disease, prior myocardial infarction and/or frequent ventricular premature beats. All were treated with either antiarrhythmic therapy or devices. DATA SYNTHESIS: Past research in the field of arrhythmia management has indicated that ventricular premature beat suppression is the key to increasing patient survival. After reviewing the results of such pivotal trials as the Cardiac Arrhythmia Suppression Trial, however, the question of whether to initiate therapy remains. CONCLUSIONS: Several trials investigating the efficacy of antiarrhythmic drugs in decreasing sudden death have yielded disappointing results. These trials have been beneficial, however, in classifying arrhythmias and assessing patient risk. The outcomes of these trials, combined with advances in the treatment of heart disease, provide us with a framework for antiarrhythmic therapy. Additional controlled clinical trials are necessary if we are to learn the best means of increasing survival in ventricular arrhythmia patients. PMID- 1307900 TI - Family-centered critical care: an option or obligation? AB - The patient was dying after undergoing aggressive treatment for a malignancy. Patient and family wanted "everything" to be done and the patient was transferred to the ICU for treatment of acute respiratory failure. The next day the patient's condition deteriorated further. The family decided against chest compressions or defibrillation; however, other aggressive treatment was continued. A "chemical code" was initiated and the patient was ventilated. The family was informed. As they stood in the hall outside the unit, the patient's wife asked if she could be with her husband. A nurse explained what she would see and accompanied her to the bedside. She stood at the head of the bed, stroked her husband's head and spoke softly in his ear. The patient's son came to the bedside and said his last words to his father. The wife was present when treatment was stopped and the patient was pronounced dead. She said to the nurse who had accompanied her, "You have given me the greatest gift possible--you allowed me to be with my husband at the end." PMID- 1307901 TI - Pacemaker update: 1992. Part I: General remarks and electrocardiographic assessment of pacemaker function. PMID- 1307902 TI - Regulations and critical care. PMID- 1307903 TI - When weaning from mechanical ventilation fails. AB - OBJECTIVE: To describe the etiologies and indicators of weaning failure and to provide a framework for planning interventions to facilitate weaning of long-term ventilation patients. DATA SOURCE: A Medline search of human studies in English on weaning from mechanical ventilation. ARTICLE SELECTION: Articles were selected if they pertained to the assessment and management of weaning failure. Both research and review articles were included. DATA EXTRACTION: All pertinent articles were described, along with their limitations. DATA SYNTHESIS: Weaning from mechanical ventilation is an emerging science. Caring for patients who are difficult to wean requires expert clinical decision making so patients do not feel defeated and have the best chances for success. Combining the limited research on weaning intervention with clinical expertise helps to build a scientific basis for care and can assist clinicians in tailoring interventions to specific problems that precipitate weaning failure. CONCLUSION: A scientific approach to care may promote weaning in difficult cases and provide directions for future research into the etiologies of weaning failure. PMID- 1307904 TI - Myocardial ischemia during the weaning period. AB - OBJECTIVES: To estimate the incidence of silent myocardial ischemia, its pattern over time and its relationship to the time and mode of weaning high-risk cardiac patients after noncardiac surgery. DESIGN: Prospective study with random assignment to one of three weaning modes. SETTING: A surgical intensive care unit in a university hospital and a Veterans Administration hospital. PATIENTS: Sixty two patients meeting standard criteria for extubation were randomized to one of three modes of weaning: synchronized intermittent mandatory ventilation (n = 19), T-Bar (n = 21) or continuous positive airway pressure (n = 22). METHODS: Ischemia was monitored with a continuous two-lead (V5, III) ST segment analyzer. Tracings were reviewed by a cardiologist. Ischemia was defined as greater than 1 mm ST segment depression 60 milliseconds after the J point. The monitoring period included a prewean (mean 654.0 minutes), wean (mean 46.5 minutes) and postwean (mean 1223.4 minutes) period. RESULTS: Of 62 patients, 12 (19.3%) experienced ischemia at some time during the monitoring period, most often during the weaning period. Ischemia during weaning was detected in 3 of 21 (14.3%) T-Bar patients and 2 of 22 (9.1%) continuous positive airway pressure patients but in no synchronized intermittent mandatory ventilation patients. CONCLUSION: This study demonstrates that silent myocardial ischemia occurs frequently in high-risk postoperative patients, with the highest incidence during weaning. PMID- 1307905 TI - Job satisfaction among critical care nurses. AB - OBJECTIVE: To develop a conceptual path model to explain the effects of a set of personal and work-related independent variables and the dependent variables of situational stress, job stress and job motivation on job satisfaction among critical care nurses. DESIGN: A prospective descriptive study using a conceptual path model. SETTING: Nine hospitals licensed for at least 250 beds in the northeastern, northwestern, northcentral, and southern regions of Florida. SAMPLE: Three hundred female critical care nurses employed in the nine hospitals who had worked full-time for at least 3 months. MEASUREMENTS: Subjects were administered a demographic and work survey questionnaire, Daily Hassles Instrument, Psychological Hardiness Test and the Job Diagnostic Inventory. MAIN OUTCOME MEASURES: A conceptual path model was constructed to illustrate the effects of a set of personal and work-related independent variables and the dependent variables of situational stress, job stress and job motivation on job satisfaction. MAIN RESULTS: Path analysis of a job satisfaction model resulted in a causal progression of situational stress leading to either job stress or job motivation, both affecting job satisfaction. The results showed that job stress, job motivation, job expectations, meaningful work, knowledge of work results, commitment to career, health difficulties, task identity, supervision, dealing with others at work, opportunity for advancement, pay and job security had a significant effect on job satisfaction. CONCLUSION: Thirteen variables had a significant effect on job satisfaction and explained 63% of the variance. The four most significant effects on job satisfaction were opportunities for advancement, meaningfulness of work, pay and supervision. Commitment to the career, task identity and job security had a modest effect on job satisfaction. PMID- 1307906 TI - Characteristics and health service utilization patterns of ventilator-dependent patients cared for within a vertically integrated health system. AB - OBJECTIVE: To describe the characteristics and service utilization patterns of long-term ventilator-dependent patients. DESIGN: Using medical records, a cohort of ventilator-dependent patients was identified and followed. SETTING: A vertically integrated healthcare system in southwestern Pennsylvania. PATIENTS: Forty-nine adults requiring prolonged ventilatory assistance. MEASURES: Demographics, admission date, admission diagnosis, discharge diagnosis, reason for ventilator dependency, level of care to which the patient was admitted, dates of all transfer orders, dates of all transfers between levels of care, discharge destination and subsequent readmissions. RESULTS: The major reason for long-term ventilator dependency was progressive debilitating disease of either a pulmonary or nonpulmonary nature. The mean length of stay within the system was 72.6 days +/- 42.55 (median = 59 days, range = 24 to 267 days). Patients had an average of 3.3 transfers +/- 2.53 within the system (median = 3, range = 0 to 10). No delays in transfer to lower levels of care were found. Health utilization variables were largely unrelated to reason for ventilator dependency. Almost half of the patients (n = 24 or 49.0%) died in the system. Patients who died in the system were significantly older than patients for whom discharge home was possible. CONCLUSIONS: Additional studies are necessary to describe the prevalence, etiology, health status and functional status of ventilator patients at all levels of care; the impact of different system approaches on patient well-being and cost of care; and the process of medical decision making. Economic analyses of costs and outcomes for ventilator-dependent patients using a cost-utility approach are also needed. PMID- 1307908 TI - Effects of a closed tracheal suction system on ventilatory and cardiovascular parameters. AB - OBJECTIVE: To determine whether patients ventilated in the assist-control mode experienced a change in oxygenation, respiratory rate, inspiratory:expiratory ratio, heart rate, blood pressure or acid-base balance when suctioned with a closed tracheal suction system. DESIGN: A quasi-experimental, within-subject, repeated-measures design was used. SUBJECTS: 18 patients ventilated on a fraction of inspired oxygen of 0.47 +/- 0.17 and 2.3 +/- 5.0 cm H2O positive end expiratory pressure. INTERVENTIONS: Two suction passes were performed, with measurements at baseline, immediately after the first suction pass, immediately before the second suction pass, immediately after the second suction pass, 2 minutes after the second suction pass and 5 minutes after the second suction pass. No hyperoxygenation was used. RESULTS: Significant differences were seen over time for arterial oxygen saturation, respiratory rate and inspiratory:expiratory ratio. Arterial oxygen saturation decreased to less than 90% in four subjects (range 88% to 89%), with a maximum fall of 9%. No significant differences were seen for heart rate, blood pressure, partial pressure of carbon dioxide, bicarbonate, time to nadir (lowest arterial oxygen saturation) or recovery time. CONCLUSIONS: Subjects ventilated in the assist control mode and suctioned with a closed tracheal suction system did not experience significant changes in cardiovascular or acid-base parameters when suctioned without hyperoxygenation. Although most subjects did not become desaturated, four subjects experienced desaturation at one or more intervals. To prevent desaturation, hyperoxygenation should be used before and after suctioning with a closed tracheal suction system. PMID- 1307907 TI - Terminal weaning from mechanical ventilation: ethical and practical considerations for patient management. AB - Decisions to withdraw life-sustaining therapy are being made more often as patients and healthcare providers increase their awareness of patient rights. The process of withdrawal of mechanical ventilation must be conducted in a humane fashion. An understanding of the ethical, legal and practical considerations for patient management during this type of intervention will enhance the ability of the healthcare provider to participate. PMID- 1307909 TI - Preventing hypoxemia and hemodynamic compromise related to endotracheal suctioning. AB - OBJECTIVE: To help the clinician bridge the gap between research and practice in determining ways to minimize side effects of endotracheal suctioning. DATA SOURCES: This article summarizes four previous reviews of research and studies published between 1984 and 1991 related to oxygenation techniques before, during and after endotracheal suctioning, and hemodynamic consequences of the suctioning procedure. STUDY SELECTION: Studies were reviewed by type of subject: animals, human subjects with normal lung function, and human subjects with abnormal lung function. Research of pediatric and head-injured populations was excluded from this review. DATA EXTRACTION: Oxygenation protocol, endotracheal suction characteristics, outcomes and measurement times, sample and setting, and findings were presented. CONCLUSIONS: Conclusions relate to the effectiveness of various endotracheal suction protocols on prevention of hypoxemia and hemodynamic compromise in intubated patients. DATA SYNTHESIS: An algorithm to guide clinical decision making is presented based on the conclusions of this review of the research. PMID- 1307910 TI - Characteristics of a child's critical illness and parents' reactions: preliminary report of a pilot study. AB - OBJECTIVE: To explore the relationships between parents' reactions to the pediatric intensive care unit admission of a child and characteristics of the child's illness. METHOD: A convenience sample, consisting of 16 mothers and 13 fathers of 16 children aged 5 years and younger, was used. The Pediatric Risk of Mortality scale was used to measure severity of illness. Parental reactions were measured at about 24 hours after the child's admission with the Parental Stressor Scale: PICU and the Parental Concerns Scale. RESULTS: Mothers' concerns and stressors were not related to the child's Pediatric Risk of Mortality score. However, fathers reported greater concern about the child's experience and about parenting as the child's Pediatric Risk of Mortality score increased. CONCLUSIONS: Parents' reactions to their child's critical illness and admission to the pediatric intensive care unit were not related to characteristics of the child's condition in this small sample. Future research needs are suggested. PMID- 1307911 TI - An evaluation of interventions for meeting the information needs of families of critically ill patients. AB - OBJECTIVE: To evaluate the effectiveness of two methods of meeting the information needs of families of critically ill patients: an open visiting hour policy and a family information booklet. SETTING: Medical intensive care unit of a university medical center. SUBJECTS: Family members (N = 147) of patients admitted to the medical intensive care unit. INTERVENTIONS: Implementation of an open visiting hour policy and information booklet. MEASUREMENTS AND MAIN RESULTS: Questionnaires were distributed to family members 24 to 48 hours after the patient's admission. The questionnaire addressed family satisfaction with having specific information needs met and posed questions that tested their knowledge of unit policies and personnel. The questionnaire was distributed to three groups: families who had restricted visiting hours and no booklet (group 1, n = 48), families who had open visiting hours but no booklet (group 2, n = 50), and families who had open visiting hours and an information booklet (Group 3, n = 49). Implementation of an open visiting hour policy increased family satisfaction. Families exposed to both the open visiting hours and the information booklet were more knowledgeable about specific details than were those exposed to only the open visiting hour policy. CONCLUSIONS: Flexible visiting hours and information booklets were two practical methods of meeting the information needs of families. Open visiting hours, as a singular intervention, significantly improved family satisfaction. The effectiveness of the booklet in assisting families to recall discrete pieces of information supports the further development and use of preprinted materials to assist in meeting family information needs. PMID- 1307912 TI - Comparison of PT and aPTT values drawn by venipuncture and arterial line using three discard volumes. AB - BACKGROUND: Blood samples obtained through heparinized arterial catheters are used routinely for a variety of laboratory tests. Accuracy of coagulation studies performed from samples obtained in this fashion continues to be questioned, particularly in regard to the minimum discard volume necessary to clear the catheter of heparinized solution. OBJECTIVE: To examine differences between prothrombin time and activated partial thromboplastin time values obtained from blood drawn by venipuncture and from an indwelling intra-arterial line using three discard volumes. METHODS: Prothrombin time and activated partial thromboplastin time samples were drawn by venipuncture from 41 critically ill adult patients. Simultaneously, three consecutive blood samples of 2.3 mL were drawn from the arterial line after an initial discard volume of 3 mL (discard volumes of 3.0, 5.3 and 7.6 mL). RESULTS: Significant differences were found between arterial and venous prothrombin time values for the 3-mL discard volume group, as well as between arterial and venous activated partial thromboplastin time values for all three discard volume groups (paired t-test, Bonferroni correction). CONCLUSION: We recommend that when drawing prothrombin time and activated partial thromboplastin time samples from an arterial line, a 5.3-mL discard volume be used. PMID- 1307913 TI - Mathematical model for agonist-induced oscillatory calcium waves in non-excitable mammalian cells. AB - Many non-excitable cells display cytosolic Ca2+ oscillations resulting from the periodic release of Ca2+ from intracellular stores. Recent observations in hepatocytes and some other cell types have shown that agonist-induced Ca2+ oscillations often display an intracellular spatial organization and do not occur synchronously within the cell. Ca2+ waves evoked by different agonists originate from the same subcellular locus and propagate through the cell with a constant rate of progress and amplitude. This indicates that Ca2+ waves are driven by a self-propagating mechanism and not by diffusion alone. We propose a simplified one-dimensional mathematical model to describe this phenomenon based on the mechanism of calcium-induced calcium release. The numerical solution of the system of two coupled non-linear partial differential equations reproduces many of the main features observed experimentally. PMID- 1307914 TI - A rare synaptoid contact between gland cells in the anterior pituitary. AB - A rare type of cell-to-cell contact has been identified between the corticotropes in the anterior pituitary of the dog. It bears synaptoid features. PMID- 1307915 TI - Antisense oligonucleotide-mediated inhibition of metallothionein protein synthesis in neuroblastoma IMR 32 and Chang liver cells in culture. AB - A synthetic antisense oligodeoxyribonucleotide with sequence complementary to the messenger RNA (mRNA) coding for human metallothionein (MT) II was prepared and tested for its ability to inhibit both constitutive- and cadmium-induced MT protein synthesis in neuroblastoma-IMR and Chang liver cells in culture. The sense oligonucleotide was also prepared and tested as a control for its sequence specific effects. Oligonucleotide entry into cells was enhanced through the use of a polybrene carrier so that nearly 30% of a 10 microM dose of oligonucleotide was shown to be associated with cells. The antisense oligonucleotide inhibition of MT protein synthesis rendered both cell types more sensitive to cadmium toxicity. However, the sense oligonucleotide had no effects on either MT protein synthesis or sensitivity to cadmium toxicity. PMID- 1307916 TI - Implication of tryptophan in the stimulatory effect of delta-sleep-inducing peptide on indole secretion from perifused rat pineal glands. AB - We have recently demonstrated that delta-sleep-inducing peptide (DSIP) stimulates indolamine secretion from rat pineal glands. In the present study, we show that tryptophan (TRP), as well as DSIP, stimulate melatonin (MEL) and 5-methoxy tryptophol (5-ML) secretion in a dose-dependent manner between 5 x 10(-6) and 10( 4) M. The kinetic characteristics of the MEL and 5-ML secretion and the response induced by the two substances were similar. The increase in MEL secretion in response to 10(-4) M DSIP was completely inhibited by pretreatment of the pineals with 10(-5) M phenanthroline (amino-peptidase inhibitor), suggesting that stimulatory effect of DSIP was due to TRP liberated by peptide degradation. This mechanism occurring in the pineal was confirmed using 10(-4) M para chlorophenylalamine (TRP hydroxylase inhibitor), which reduced the pineal response to 10(-4) and 10(-5) M DSIP by 50 and 100%, respectively. PMID- 1307917 TI - Inhibitory action of peptide YY on pancreatic secretion is independent of secretin. AB - The purpose of this study was to characterize the effect of peptide YY (PYY) on acid-stimulated pancreatic bicarbonate secretion and to determine whether PYY affects the release of secretin in response to intraduodenal infusion of acid. Six dogs were prepared with gastric and pancreatic cannulas. In study 1, graded doses of hydrochloric acid (HCl) (3, 6, 12, and 24 mEq/h) were given intraduodenally alone or in combination with intravenous PYY (400 pmol/kg.h). In study II, and ED50 of intraduodenal HCl (6 mEq/h) was given alone or in combination with graded doses of PYY (12.5, 25, 50, 100, 200, and 400 pmol/kg.h, i.v.). Bicarbonate output was significantly inhibited during PYY infusion at 200 and 400 pmol/kg.h, but plasma secretin levels were unchanged. The calculated maximal response for bicarbonate secretion (5.1 +/- 1.3 mEq/15 min) was significantly reduced by PYY (2.1 +/- 0.7 mEq/15 min). We concluded that PYY can inhibit acid-stimulated pancreatic bicarbonate secretion without affecting the release of secretin. The mechanism of the inhibitory effect of PYY on acid stimulated pancreatic bicarbonate secretion is compatible with a noncompetitive type of inhibition. PMID- 1307918 TI - Effect of a cholecystokinin antagonist, proglumide, on cholecystokinin-8-induced gallbladder contraction in conscious dogs. AB - The objective of this study was to characterize the effect of proglumide, a cholecystokinin (CCK) antagonist, on gallbladder contraction stimulated by CCK in conscious dogs. The gallbladder contraction was monitored by a strain-gauge force transducer that was chronically sutured onto the serosal surface of the gallbladder. The results of this study show that proglumide, given as an intravenous bolus (2.5, 5, 10, 20, and 40 mg/kg) or as a continuous intravenous infusion (150 or 300 mg/kg/h, 10 min), can block the stimulatory action of CCK in a dose-related manner. Bolus administration of proglumide resulted in a transient inhibition, whereas continuous infusion of proglumide resulted in a prolonged antagonism of CCK-stimulated gallbladder contraction. Review of the data leads to the conclusion that the antagonistic action of intravenously administered proglumide on CCK-stimulated gallbladder contraction may be characterized as rapid and reversible. PMID- 1307919 TI - Isomorphism, task dependence, and the multiple meaning theory of neural coding. AB - The neural coding problem is defined and several possible answers to it are reviewed. A widely accepted answer descends from early suggestions that neural activity, in general, is isomorphic with sensation and that the biological signals resident in the axons of neurons, in particular, are given by their frequency of firing. More recent data are reviewed which indicate that the pattern of neural responses may also be informative. Such data led to the formulation of the multiple meaning theory which suggests the neural pattern may encode different information features in single responses. After a period in which attention turned elsewhere, the multiple meaning theory has quite recently been revived and has stimulated novel and careful experimental investigations. A corollary theory, the task dependence hypothesis, suggests that these information bearing multiple response features are accessed differentially in different behavioral tasks. These theories place stringent temporal requirements on the generation and analysis of neural responses. Recent data are examined indicating that both requirements may indeed be satisfied by the nervous system. Finally, several methods of experimentally testing such coding theories are described; they involve manipulating the biological signals of neurons and observing the effect of these manipulations on behavior. PMID- 1307920 TI - Nicotinic versus muscarinic binding sites in cat and rabbit carotid bodies. AB - It has been suggested that acetylcholine (ACh) might play an important role in carotid body chemoreception. However, a unified explanation of the actions of ACh in this organ has been lacking, due in part to the opposite pharmacological effects of this agent on carotid sinus nerve discharge in different animal species, most notably the cat, where ACh is excitatory, versus the rabbit, where it is inhibitory. In the present study, we utilized receptor binding techniques to compare the nicotinic and muscarinic receptor populations in the carotid bodies of these two species. Our results with the nicotinic ligand 125I-alpha bungarotoxin and the muscarinic ligand 3H-quinuclidinyl benzilate suggest that nicotinic receptors predominate in the cat by a ratio of 2:1, while in the rabbit, a 12:1 ratio favors muscarinic receptors. Our data suggest that the relative numbers of muscarinic and nicotinic receptors in the carotid bodies of these two species determine the excitatory or inhibitory actions of exogenously administered ACh in this chemoreceptor organ. PMID- 1307921 TI - Flight effects on plasma levels of neurohypophysial hormones in homing pigeons. AB - A significant increase in the circulating levels of arginine vasotocin (AVT), without change in plasma osmolality, was observed in homing pigeons immediately after a flight of 48 km, lasting 60-80 min. This increase in plasma AVT is perceived as part of an overall homeostatic mechanism of mobilizing lipid as fuel for the flight muscles, of water conservation and temperature regulation in the body during the homing flight within the specific distance and duration of flight and under normal weather conditions. However, there was no change in plasma levels of mesotocin (MT) which suggests that the birds were under no significant stress during the flight. PMID- 1307922 TI - Effects of anticoagulants and incubation time on neutrophil nitroblue tetrazolium score. AB - We studied the effect of anticoagulants and incubation time on neutrophil nitroblue tetrazolium (NBT) scores. Heparin (10 IU/ml) and EDTA (1.5 mg/ml) were used, and the preparations were incubated for periods ranging from 20 to 180 min. Heparin, in contrast to EDTA, was found to be associated with cell destruction, cell aggregates and higher NBT scores; the effects were more profound with endotoxin stimulation. The duration of incubation significantly affects NBT scores in both the heparin- and EDTA-anticoagulated samples, and the effect is more marked with heparin. Cell destruction and cell clumping are both enhanced with incubation, again more so with heparin. It is concluded that when performing NBT tests, blood samples would best be anticoagulated with EDTA to ensure more consistent results. PMID- 1307924 TI - Light-related melatonin changes in pituitary response to gonadotropin-releasing hormone during sexual development in the female rabbit. AB - Melatonin levels in the blood of female rabbits were determined from the time of weaning to adulthood in a longitudinal study. Blood samples were taken at 3 h after light onset and 1 h after dark onset and plasma was analysed for melatonin, LH and FSH by radioimmunoassay procedures. The animals were sacrificed on days 25, 32, 39, 51, 72, 91 and 120 days of life and pituitaries removed for in vitro incubation of slices to determine their response to GnRH. Circulating melatonin levels were significantly higher in the dark compared to the light phase and peaked on days 72 and 91 when gonadotropin levels were at a nadir. Melatonin levels on day 120 were lower than those on any other day examined. Basal secretion of LH and FSH by pituitary slices in vitro increased several-fold from day 25 of age to days 51-91 and then decreased by day 120. The pituitary gonadotropin responsiveness to GnRH in vitro was also different: while LH generally increased, FHS accumulation remained constant after GnRH stimulation. These data suggest that the female rabbit pituitary undergoes changes in sensitivity to GnRH during sexual maturation and that the pineal gland may play a role in this process. PMID- 1307923 TI - Insulin-like growth factors. AB - The insulin-like growth factors (IGF-I and IGF-II) play important roles in the regulation of growth and metabolism. While the liver is the main source of circulating IGFs, their production by numerous extrahepatic tissues suggests the existence of autocrine and paracrine modes of action in addition to typical endocrine mechanisms. The actions of the IGFs are mediated through their activation of specific cell surface receptors, primarily the IGF-I receptor, although some effects may be mediated through the IGF-II receptor and the insulin receptor. The stability of the IGFs and their interaction with their receptors are mediated by specific IGF binding proteins (IGF-BPs) which are found in the circulation and in extracellular fluids. Thus, the overall biological actions of the IGFs can be regulated by control of ligand biosynthesis, modulation of receptor levels and postreceptor signalling pathways, and changes in the levels and activity of IGF-BPs. PMID- 1307925 TI - Genistein inhibits DNA synthesis but has no effect on levels of DAG and IP3, cell rounding and alkalinization in sulphate-treated Chang liver cells. AB - Agonist-activated phosphoinositide (PI)-specific phospholipase C initiates PI hydrolysis to produce signals implicated in mitogenic signaling in which the cyclin-dependent cdc2-protein kinase of the maturation-promoting factor is a major protein-tyrosine kinase (PTK) substrate. It has been suggested that PI mitogenic signals are separable into PTK-dependent and non-PTK-dependent by genistein, a tyrosine-specific protein kinase inhibitor. However, we show here that DNA synthesis was abolished in human Chang liver cells although the sulphate induced PI second messengers, i.e. inositol 1,4,5-trisphosphate and sn 1,2,diacylglycerol, were at equivalent dose-response levels with or without genistein (0.5 mM, 135 microgram/ml). This genistein dosage had been demonstrated to be effective in suppressing tyrosyl phosphorylation in cells. There was no increase in the trypan blue dead cell index. We have shown previously that human Chang cells stimulated by this 'non-growth-factor' agonist, i.e. sulphate, as well as extracellular ATP, became rounded with raised intracellular pH. ATP induced cell rounding and intracellular alkalinization were not affected by the presence of genistein (0.5 mM). In the present investigation, that genistein dosage had also no effect on these cellular responses when initiated by added sulphate. It seems that the mitogenic signaling function of PI second messengers is dissociable and requires unsuppressed PTK activity. PMID- 1307926 TI - Binding of [125I]-labelled iodomelatonin in the duck thymus. AB - [125I]-labelled iodomelatonin binding sites in membrane preparations of duck thymus were studied. The specific binding of [125I]-labelled iodomelatonin in the duck thymus was stable, saturable, reversible and of high affinity. Scatchard analysis of the binding of [125I]-labelled iodomelatonin in the duck thymus collected at midlight had an equilibrium dissociation constant (Kd) of 34.8 +/- 9.4 pmol/l and a maximum number of binding sites (Bmax) of 0.98 +/- 0.07 fmol/mg protein. Two-point diurnal study demonstrated that the Bmax in samples collected at midlight was 42.0% higher (p < 0.05) than that at middark, but there was no significant difference (p > 0.05) between the midlight and middark Kd values. Competition inhibition studies showed that only melatonin, 2-iodomelatonin, 6 chloromelatonin, 6-hydroxymelatonin, N-acetylserotonin, 5-methoxytryptophol, and 5-hydroxytryptamine showed significant inhibition of the [125I]iodomelatonin binding in duck thymus membrane preparations, while the other compounds had no significant inhibition. Our results suggested a direct action of melatonin on the thymus and, thus, the cellular immune system. PMID- 1307928 TI - Neurotensin secretion in response to intraduodenal and intraileal administration of fat in dogs. AB - Release of neurotensin from the small intestine in response to administration of fat directly into the duodenum and ileum was examined in conscious dogs. The present results show that: (1) intraduodenal administration of fat causes a diphasic release of neurotensin which is mediated, at least in part, by cholinergic mechanisms, and (2) both a fatty acid (sodium oleate) and a triglyceride, when infused directly into an isolated ileal loop, stimulate a significant release of neurotensin. Our findings indicate that release of neurotensin is triggered by mechanisms originating in the proximal small intestine and by a direct contact of nutrients with the ileal mucosa. PMID- 1307927 TI - Localization of GTP-binding protein Go in the enteric nervous system in rat ileum. AB - The localization of a GTP-binding protein G(o) was examined immunohistochemically in rat ileum using antibodies against the alpha-subunit of G(o) (G(o) alpha). G(o) alpha-positive fibers clearly demonstrated the topography and structure of the enteric nervous system of the ileum. G(o) alpha was present only in the nervous system and was generally distributed both in synapse-rich and in nonsynaptic areas. The distribution of G(o) alpha in a nonsynaptic area suggests the possibility that G(o) may be involved not only in neurotransmission mechanisms but also in other functions. PMID- 1307929 TI - Extraction, discrimination and analysis of single-neuron signals by a personal computer-based algorithm. AB - We communicated a computer algorithm that is capable of concurrently extracting, discriminating and analyzing single-neuron signals from adjacent neurons, particularly those with poor signal-to-noise ratio or contaminated by 60-Hz noise and/or baseline drift. Based on a continuous process of differentiation and peak to-peak amplitude discrimination, our algorithm provided a two-dimensional amplitude histogram that readily distinguishes the clusters of spike signals representing different neurons. The inclusion of a time domain in our three dimensional amplitude histogram further allowed us to simultaneously evaluate the temporal responses of neighboring cells to the same experimental manipulation. In addition to retaining many of the advanced features of existing extraction and discrimination procedures, this method offered the benefits of being efficient, requires minimal supervision and operates in real time even during long-term recording. Above all, it is cost effective because it is purely software based and only requires a PC-AT compatible general purpose computer. PMID- 1307930 TI - Synthetic antisense oligonucleotide probes the essentiality of metallothionein gene. AB - The metallothionein II gene, whose structure is highly conserved throughout the animal kingdom, is composed of three exons and two introns. Synthetic antisense oligonucleotides (ODN), with sequence complementary to the messenger RNA coding for human metallothionein II, were prepared and tested for their ability to inhibit both constitutive- and cadmium-induced metallothionein protein synthesis in human Chang liver cells and hamster lung V79 cells in culture. The property of sense ODN was also examined as a measure of sequence specificity. The antisense inhibition of metallothionein protein synthesis rendered all cell lines more susceptible to the toxic effects of cadmium. However, the sense ODN had no effects on either metallothionein protein synthesis or sensitivity to cadmium. Phosphorothioate oligonucleotides were more potent in enhancing the toxicity of cadmium than phosphodiester oligonucleotides. The antisense oligonucleotides targeted to the splice donor region between exon 1 and intron 1 was significantly more effective as an inhibitor than those targeted to either the 5' end of the mRNA or within exon 3. Therefore, not all antisense oligonucleotide sequences are equally efficient as inhibitors of metallothionein synthesis. Therefore, the delineation of an obvious mechanism for predicting the most potent sequence is not apparent at this time. The results of this study are interpreted to indicate that (a) metallothionein is endowed with an essential gene, (b) modifications in oligonucleotide structures show specificity in inhibiting metallothionein synthesis, and (c) antisense inhibition of metallothionein gene expression may provide a useful tool in studying the action and perhaps the function(s) of metallothionein. PMID- 1307931 TI - [125I]iodomelatonin-binding sites in the chicken kidney: characterization and comparison to other avian species. AB - The existence of [125I]iodomelatonin-binding sites in the kidney of the chicken and other avian species has been demonstrated in the present study. [125I]Iodomelatonin-binding sites in membrane preparations of the chicken kidney were reversible, saturable, specific and of high affinity. Scatchard analysis of the specific binding revealed an equilibrium binding constant (Kd) of 30.3 +/- 5.1 pmol/l (n = 5) and a total number of binding sites (Bmax) of 2.89 +/- 0.24 fmol/mg protein (n = 5) at the middle of the light period (mid-light). The Hill coefficient approached 1.0, suggesting a single class of [125I]iodomelatonin binding sites in the chicken kidney. The diurnal variation study showed that the Bmax was 52% higher at mid-light than that in the middle of dark period (1.90 +/- 0.33 fmol/mg protein, n = 4; p < 0.05), with no significant variation in Kd. The Kd value determined from kinetic analysis was 10.8 pmol/l in the mid-light birds, which was comparable to values determined from equilibrium studies. The competition inhibitor experiments demonstrated that [125I]iodomelatonin-binding sites were highly specific for melatonin with the following order of potency: 2 iodomelatonin > melatonin, 6-chloromelatonin > 6-hydroxymelatonin N acetylserotonin >> 5-methoxytryptamine, 5-methoxytryptophol, 5-hydroxyindole-3 acetic acid, 5-hydroxytryptamine, 1-acetylindole-3-carboxaldehyde, 3 acetylindole, tryptamine, 5-methoxyindole-3-acetic acid, L-tryptophan, harmaline, acetylcholine, epinephrine and norepinephrine. Studies on the relative binding density of [125I]iodomelatonin to the kidney in different species of birds showed the following descending order: duck > chicken > pigeon > quail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307932 TI - Nonendothelial aortic source of nitric oxide in Wistar-Kyoto normotensive and spontaneous hypertensive rats. AB - Using a recognized inhibitor of nitric oxide (NO) synthesis, Nw-nitro L-arginine methyl ester (L-NAME), we tested the hypothesis of the existence of a nonendothelial source of NO in vascular tissue using rings of rat thoracic aorta in which endothelial cells have been removed by mechanical abrasion and have totally lost their endothelium-dependent relaxation. Contractility of the muscle was tested by recording the concentration-dependent contraction of the preparations induced by an alpha-adrenergic agonist, phenylephrine. Contractility in aortas from Wistar-Kyoto normotensive rats (WKY) and spontaneous hypertensive rats (SHR) was not significantly affected by a 30-min to 2-hour incubation with L NAME prior to agonist stimulation. However, preparations incubated for 30 min with 1 mM L-arginine (L-ARG) and then washed for 1 h in standard Krebs solution had a significantly reduced contraction to phenylephrine in both WKY and SHR. In these preparations pretreated with L-ARG, L-NAME significantly increased contractility in both WKY and SHR; this effect was prevented by L-ARG but not by D-arginine. Responses to phenylephrine were not inhibited by L-ARG when preparations were incubated from the beginning of the experiment with 1 mM cycloheximide, thus suggesting a dependence on protein synthesis of the attenuation of contraction seen with L-ARG. Intact aortic rings processed for NADPH diaphorase histochemistry, a putative marker for NO synthase, showed NADPH diaphorase reactivity only in the endothelial layer and in the adventitia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307933 TI - Characteristics of (-)-stepholidine on the firing activity of substantia nigral dopamine neurons after repeated reserpine treatment. AB - Although (-)-stepholidine [(-)-SPD] exhibits antagonistic effects to normosensitive dopamine (DA) receptors, it shows agonistic effect (probably D1) on rotational behavior in rats with unilateral 6-OHDA lesions of substantia nigra pars compacta (SNC). In this study, another supersensitive model, reserpinized rats (1 mg/kg x 6 days, s.c.), were used to investigate the properties of (-) SPD. In reserpinized rats, (-)-SPD reversed and/or significantly attenuated the firing inhibition caused by the mixed DA receptor agonist apomorphine (APO). After reserpinization, the selective D1 and D2 receptor agonists separately inhibited the firing rate of SNC DA neurons, and (-)-SPD reversed both D2 receptor agonist N-0437- and D1 receptor agonist SKF 38393-induced inhibition of the SNC DA cell firing. These results suggest that (-)-SPD shows D1 and D2 receptor antagonistic action and does not possess the same DA receptor agonistic effect on SNC DA cell firing activity in reserpinized supersensitive rats as it does in unilateral 6-OHDA-lesioned rotational behavior. Also, large doses of (-) SPD inhibited the firing rate of SNC DA cells in reserpinized rats, but the inhibition was not reversed by D1 receptor antagonist SCH 23390 but was reversed by N-0437 or APO. This inhibition, thus, could be interpreted as depolarization inactivation (DI) due to blockade of DA receptors. Interestingly, in control (nonreserpinized) rats, (-)-SPD did not produce DI of SNC DA cells as it did on ventral tegmental area DA cells. These results imply that reserpinization modulates the onset of DI of SNC DA cells and that (-)-SPD may serve as a leading compound for exploring new types of atypical neuroleptics. PMID- 1307934 TI - Role of stroma in oestrogen-induced epithelial proliferation. AB - To examine the role of stromal-epithelial interactions in the response of epithelial cells to oestrogens, tissue recombinations were prepared with epithelium (E) and stroma (S) from the vagina (V) and urinary bladder (BL), that is between oestrogen target tissues (VS and VE) and non-target tissues (BLS and BLE). Following 3 weeks of growth in intact female hosts, ovariectomy was performed and 1 week later the hosts subjected to various hormonal treatments. Whereas homotypic vaginal tissue recombinations (VS+VE) exhibited epithelial cornification and mucification (cycling), this activity was not observed in homotypic bladder recombinants (BLS+BLE) or in heterotypic tissue recombinants between vaginal and bladder tissues (VS+BLE and BLS+VE). In BLS+VE recombinants the epithelium remained atrophic and failed to respond to exogenous oestrogen alone or in combination with progesterone. This lack of hormonal responsiveness of vaginal epithelium was completely reconstituted when the epithelium of BLS+VE recombinants was recovered and reassociated with fresh vaginal stroma (VS). Examination of epithelial proliferative activity ([3H]thymidine labelling index) demonstrated a marked oestrogen-induced increase in epithelial proliferation in VS+VE recombinants. BLS+BLE recombinants were unresponsive to oestrogen as were recombinants composed of BLS+VE. However, when bladder epithelium was grown in association with vaginal stroma (VS+BLE) the epithelium exhibited an 8-fold oestrogen-induced increase in labelling index over oil-treated specimens. The lack of an oestrogen-induced proliferative response of vaginal epithelium in BLS+VE recombinants was reversed when the vaginal epithelium of these recombinants was recovered and reassociated with fresh vaginal stroma. These results indicate that the effects of oestrogen and progesterone on both epithelial differentiation and proliferation are critically dependent upon the appropriate stromal environment. PMID- 1307935 TI - Circadian variations in cell cycle phase progression of mouse epidermal cells measured directly by bivariate BrdUrd/DNA flow cytometry. AB - Circadian stage-dependent variations in cell cycle traverse of mouse epidermal cells in vivo were investigated. The fate of cohorts of basal cells pulse labelled with bromodeoxyuridine (BrdUrd) at different times of the day were studied by bivariate BrdUrd/DNA flow cytometry of isolated epidermal basal cells. Basal cells were tracked through the cell cycle up to 96 h after intraperitoneal injection of BrdUrd at 0800 and 2000, or followed for 6 h after BrdUrd injection at 0400, 1200, 1600 and 2400. The results confirmed our previous assumption that the cell cycle progression through S phase and G2 phase is considerably delayed at night, i.e. from 1600 to 0400, compared with daytime. The results indicate variations in G1 phase as well. The data strongly support the hypothesis that the main parameters responsible for circadian fluctuations in mitotic activity are variations in the S and G2 phase durations. The data are also consistent with the notion of proliferative heterogeneity among basal cells as described by a hierarchical proliferation model. PMID- 1307936 TI - Clinical applications of cultured epithelium. AB - Techniques that allowed the successful serial subcultivation of human keratinocytes into sheets of epithelium suitable for grafting have made possible a variety of clinical applications for cultured epithelium. Following the first description of this technique in 1981 to treat third-degree burns, cultured keratinocytes derived from a small biopsy of the patient's normal skin (autografts) have been used in centres throughout the world to provide permanent wound coverage for extensive burns. Over the years, applications have expanded to include the treatment of leg ulcers and blistering skin disorders. A further development in this field has been the use of cultured epithelium derived not from the patients own skin, but from an allogeneic donor (cultured allograft). Cultured allografts have also been widely used in the treatment of burns, leg ulcers, the donor sites for split-thickness grafts, and other dermatological disorders. These allografts seem to act as a potent stimulus to wound healing, but do not survive permanently on the wound bed. Their postulated mechanism of action is through release of multiple cytokines that stimulate epithelialization from the wound periphery as well as from adnexal elements within the wound bed. Allograft application is a simple outpatient procedure which involves no discomfort for the patient. No skin biopsy is necessary and cryo-preservation of grafts for future use is possible. PMID- 1307937 TI - Identification of an 85-100 kDa glycoprotein as a cell surface marker for an advanced stage of urothelial differentiation: association with the inter-plaque ('hinge') area. AB - Although bladder cancers account for almost 5% of all human cancer deaths, little is known about the biochemistry of urothelial differentiation. We have recently identified three major protein subunits ('uroplakins') of asymmetric unit membranes (AUM), which form rigid-looking plaques covering up to 70% of the apical surface of urothelial superficial (umbrella) cells. The ordinary-looking plasma membranes that interconnect these plaques are believed to be functionally specialized, serving as flexible but durable 'hinges'. Whether these hinge membranes are biochemically unique is unknown. Using a new monoclonal antibody (AE32) we have identified an 85-100 kDa glycoprotein (UGP85) which appears to be urothelium-specific. In both normal urothelium and cultured urothelial colonies this cell surface protein is associated mainly with superficial cells, suggesting that its expression is differentiation dependent. Results from in vitro translation experiments indicated that this glycoprotein contains a core polypeptide of about 55 kDa. Using immunogold localization techniques, we showed that in cultured urothelial colonies--which are known to lack mature AUM plaques- UGP85 is distributed relatively uniformly on the apical surface of some differentiated cells. However, in superficial cells of normal urothelium UGP85 is mainly associated with the hinge areas. These results raise the possibility that UGP85 is a plasma membrane component which can be excluded, to varying extents, from the plaque region as 12 nm protein particles are assembled into a tightly packed paracrystalline AUM structure. The identification of UGP85 provides the first evidence that the hinge areas interconnecting the urothelial plaques are biochemically distinguishable from the plasma membranes of the relatively undifferentiated urothelial cells of the lower cell layers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307938 TI - Changing patterns in incidence of non-melanoma skin cancer. AB - Surveillance of skin cancer is important to evaluate prevention programmes and to monitor the effect of stratospheric ozone depletion. Evidence available from a limited number of studies suggests that incidence rates of basal cell carcinoma and squamous cell carcinoma have been increasing for at least two decades. In white populations in the United States, Canada and Australia, average annual increases of 3%-7% for basal cell carcinoma and 2%-8% for squamous cell carcinoma have been observed, though variation in ascertainment levels or changes in treatment practices during the study periods may have contributed to these apparent changes in incidence patterns. PMID- 1307939 TI - The migration pathway of epithelial cells on human duodenal villi: the origin and fate of 'gastric metaplastic' cells in duodenal mucosa. AB - The specific migration pathways which epithelial cells take as they migrate through the human villus is unknown, although there have been several speculations. The well-known phenomenon of 'gastric metaplasia' in the human duodenum is readily demonstrable by the diastase periodic acid Schiff (dPAS) method. However, there is no general agreement on whether the origin of this cell lineage is the villus epithelial cells or proliferative crypt cells. Using serial sections, model building and computer-aided three-dimensional reconstruction we have followed the pathway of migration of these metaplastic cells in human duodenal villi and report: (1) that these cells migrate in straight lines; (2) that migration is in relatively tight cohorts or migration streams; (3) that a single vestibule can supply cells to more than one villus; and (4) that the cell lineage has a complex origin, deriving either from Brunner's gland duct epithelium or from basal buds growing out of the crypts of Lieberkuhn. PMID- 1307940 TI - Possible non-functional crypts in small intestine defined using mouse aggregation chimaeras. AB - We have identified a minor population of crypts in small intestine which do not appear to export cells to villi. These crypts can be observed in whole-mounts of small intestine prepared from C57BL/6J<-->SWR mouse aggregation chimaeras stained with a peroxidase conjugate of the lectin Dolichos biflorus agglutinin (DBA-Px). In preparations where by chance the C57BL/6J epithelium (positive staining) forms only a minor component of the chimaera, occasional crypts occur which are isolated from larger patches of C57BL/6J epithelium and are surrounded by SWR (non-staining) epithelium. Fifty-one of 383 isolated C57BL/6J crypts (13%) did not appear to export cells to villi, although the crypt mouth is surrounded by a small patch of C57BL/6J epithelium on the intervillus gut floor. PMID- 1307941 TI - Role of epithelial-mesenchymal interactions in the differentiation and spatial organization of visceral smooth muscle. AB - Uterine mesenchyme from newborn (0-day) rats was grown in association with epithelia from the adult cornea, urinary bladder, oesophagus, mammary gland, 1 day skin, and 1-day uterus. Following 1 month of growth, the differentiation of uterine mesenchyme into actin-positive smooth muscle cells was assessed immunocytochemically with antibodies to smooth muscle actin. Whereas grafts of uterine mesenchyme produced only small amounts of myometrium, all types of epithelia induced extensive myometrial differentiation in the uterine mesenchyme, which indicates that this effect is non-specific. The role of cell-cell interactions in the morphological patterning of smooth muscle layers was assessed by analysing tissue recombinants composed of adult prostatic epithelium (PRE) plus mesenchyme of the urogenital sinus (UGM), or seminal vesicle (SVM), or adult bladder epithelium (BLE) plus UGM or SVM. Prostatic ducts developed in all of these tissue recombinants (UGM + BLE, SVM + BLE, UGM + PRE and SVM + PRE). When UGM was used (UGM + PRE and UGM + BLE recombinants), actin-positive smooth muscle cells became organized into thin sheaths resembling the prostatic pattern. Conversely, when SVM was grown in association with PRE or BLE, the induced prostatic ducts were surrounded by thick layers of smooth muscle cells exhibiting the seminal vesicle pattern of organization. Smooth muscle cells were unorganized in grafts of SVM or UGM alone. These observations suggest that in male urogenital glands the mesenchyme dictates the spatial organization of the smooth muscle layers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307942 TI - Extracellular matrix of enamel and the ameloblast. PMID- 1307943 TI - Developmental response of adult mammary epithelial cells to various fetal and neonatal mesenchymes. AB - Adult mouse mammary epithelial cells were isolated and grown in combination with mesenchyme from the following sources: embryonic preputial gland, foot skin, tail skin, genital tubercle skin, mammary gland, and neonatal uterus, vagina and urinary bladder. Following 1 month of in vivo cultivation of the tissue recombinants as grafts underneath the renal capsule of normal female or hyperprolactinaemic (pituitary-grafted) hosts, the specimens were analysed histologically and immunocytochemically for the expression of milk proteins, smooth muscle actin, and cytokeratins. Mesenchymal effects on adult mammary epithelium varied with the source of the mesenchyme and the hormonal status of the host. In normal female hosts preputial gland mesenchyme induced extensive mammary epithelial growth and ductal branching morphogenesis with epithelial differentiation and ductal pattern being comparable to that observed in homotypic recombinants composed of mammary gland mesenchyme plus adult mammary epithelium. Other mesenchymes (from foot, tail, genital tubercle and uterus) preserved ductal morphology and normal epithelial differentiation, but elicited minimal epithelial growth and branching morphogenesis in adult mammary epithelium. In association with urogenital sinus, vaginal or bladder mesenchymes ductal branching morphogenesis of the mammary epithelium was absent or greatly distorted and the epithelium exhibited a stratified cuboidal phenotype even though considerable epithelial growth had occurred. In hyperprolactinaemic hosts (which received a pituitary graft) epithelial growth, alveolar morphogenesis, and synthesis of casein and milk fat globule protein was stimulated in all tissue recombinants although to different extents. Alveolar morphogenesis and milk protein expression were extensive in tissue recombinants prepared with mesenchyme from embryonic mammary gland, preputial gland, tail skin and urinary bladder, but were minimal in tissue recombinants prepared with foot or genital tubercle skin. Few milk protein-positive alveoli formed in tissue recombinants composed of mammary epithelium combined with urogenital sinus or vaginal mesenchyme, even following growth in pituitary-grafted hosts. These findings demonstrate: (1) that adult mammary epithelial cells are responsive to the growth-promoting influences of heterotypic embryonic and neonatal mesenchymes; (2) that mammary growth and branching morphogenesis are induced to variable extents by different mesenchymes; (3) that fibrous (non-adipose) mesenchymes are effective inducers of mammary epithelial development; and (4) that the ability to form alveoli and produce milk proteins in adult mammary epithelial cells is critically dependent upon the nature of the connective tissue environment. PMID- 1307944 TI - Mouse embryonic palatal epithelial sheets in culture: an immunocytochemical study of proliferative activity using bromodeoxyuridine. AB - Mouse secondary palate morphogenesis is accompanied by distinctive patterns of proliferation in the palatal epithelium which latterly reflect its region specific differentiation into oral, nasal and medial edge phenotypes. Isolated intact embryonic palatal epithelial sheets were cultured prior to, and during, the critical period of epithelial differentiation in chemically defined culture medium with, and without, 10% donor calf serum. The spatial and temporal patterns of proliferative activity were investigated by immunocytochemistry in 'pulse' and 'continuous' labelling experiments using bromodeoxyuridine (BrdUrd). Continuously labelled cultures exhibited extensive proliferation throughout the oral, nasal and medial edge regions. Pulse labelled cultures demonstrated a shift in mitotic activity from nasal to oral epithelial cells probably representing the cell turnover associated with the respective differentiated phenotypes. Medial edge cells became post-mitotic within the first 19 h of culture. Our defined culture system coupled with the immunocytochemical detection of cell proliferation using BrdUrd offers a rapid and precise method for the further investigation of palatal epithelial proliferation and its regulation by extrinsic factors. PMID- 1307945 TI - Beta actin expression and organization of actin filaments in colorectal neoplasia. AB - Several studies have linked abnormal actin cytoskeletal organization and mutant actin genes with neoplastic transformation. Using in situ hybridization techniques we looked at expression of beta actin mRNA at a cellular level in normal, benign and neoplastic human colorectal tissues and correlated the level of expression with the extent of actin cytoskeletal organization in sequential sections. Normal tissues showed light labelling with the actin riboprobe, but non neoplastic crypts, with evidence of regeneration and repair, showed greater levels. Higher levels of actin mRNA expression were found in adenomas and metaplastic polyps, but the highest levels were found in carcinomas, particularly those that were poorly differentiated. Cytoskeletal actin organization was, however, reduced in colorectal neoplasia. Normal mucosa showed the highest level of cytoskeletal actin organization, as assessed by phalloidin binding, and adenomas and metaplastic polyps also stained strongly. In contrast, phalloidin binding to poorly differentiated carcinomas was absent or very weak. The inverse relationship between actin mRNA expression and actin filament organization was confined to the carcinomas studied and may indicate defects in actin binding proteins or in post-transcriptional or translational events. PMID- 1307946 TI - A comparison of in vivo cell proliferation measurements in the intestine of mouse and man. AB - Using tritiated thymidine (3HTdR) labelling in vivo in the mouse we have determined the labelling index (LI%) at each cell position along the sides of sections of crypts in the small and large bowel. We have compared LI versus cell position frequency plots obtained in this way with those obtained using bromodeoxyuridine (BrdUrd) in vivo in the small intestine. Both thymidine analogues give identical patterns and similar levels of labelling: for example, the overall LI is 29.1% after 3HTdR and 34.7% after BrdUrd in the mouse ileum. Similar data have been obtained following in vivo labelling in humans with BrdUrd prior to gastrointestinal surgery for cancer and in mouse colon following 3HTdR labelling. Comparisons between the mouse and human data show that the spatial distribution of label within the crypts occurs at the same relative positions in the two species. However, the intestinal crypts are between 2-fold and 4-fold larger, particularly in their length, in the human: for example, 250 and 450 cells per crypt for ileum and 590 and 2000 cells per crypt for the colon in mouse and human respectively. The absolute value of the maximum LI in the mouse small intestine (56.5%) is higher than it is in the human (26.3%). However, the patterns of proliferation are similar in the two species under steady-state conditions. PMID- 1307948 TI - Models of oestrogen action: a cell kineticist's view. PMID- 1307947 TI - Differential adhesion of rat colon carcinoma cells to fibronectin in relation to their tumorigenicity. AB - We examined the fibronectin-adhesive properties of clones from a rat colonic cell line exhibiting distinct tumorigenicity in a syngeneic host. These cells were originally selected on the basis of differential adhesion to plastic surfaces. The TR cell line, when injected subcutaneously, forms a tumour which grows progressively and gives off metastases, whereas the TS cell line forms a small tumour which regresses within a few weeks. The regression is largely mediated by immunological factors and involves a fibroblastic reaction. REGb, a clone from the TS subline, adhered better to fibronectin or RGDS tetrapeptide than did PROb, a clone from the TR subline. However, there was little binding to the RGD tripeptide with either clone. The degree of adhesion was dependent on time and substrate concentration. After 6 h of incubation, 38% and 55% respectively of PROb and REGb cells bound to plates coated with 10 micrograms/ml fibronectin. Adhesion of both clones to fibronectin was inhibited to various degrees when cells were preincubated with RGDS, GRGDS or GRADSPK peptides, whereas other synthetic peptides such as RGD, GRGD or GRGFSPK were ineffective. Binding experiments using 125I-labelled fibronectin showed 39,000 fibronectin receptor sites on REGb cells but only 17,000 on PROb cells. Flow cytometry analysis using both anti-alpha 5 and anti-beta 1 integrins showed more fibronectin receptor sites on REGb than on PROb cells. Both approaches were in accordance with the higher adhesiveness of the REGb clone to fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1307949 TI - [Digital image processing of radiography of 32 cases with mandible sarcomas]. AB - The radiographys of 32 cases with mandible sarcoma were analysed with digital image processing. The processed image of fibrosarcoma showed many scattered fine grains after the X-ray film were edge detected. In the same processing, the image of chondrosarcoma showed many little rings or arc structures. For osteosarcoma, the processed image showed very irregular veins. These digital processing pictures can help us to differentiate mandible sarcomas. PMID- 1307950 TI - [Detection of DNA G+C mol% in taxonomy of Streptococcus mutans by means of high performance liquid chromatography]. AB - In the present study, DNA G+C mol% of 9 strains of bacteria (including 7 international standard strain, Ingbritt, and 2 other strains extracted in our Lab) were detected with application of High Performance Liquid Chromatograph. The results showed that DNA G+C content of S. mutans was 35-40%, S. sobrinus was 45 46%, S. cricetus was 38%, and S. rattus was 41%. The difference between S sobrinus and S. mutans was higher than 5%, which suggested that S. sobrinus should be identified as an independent classification unit of bacterial species from S. mutans. PMID- 1307951 TI - [Quantitative analysis of blood flow changes measured by radioactive microsphere technique after segmental anterior maxillary osteotomy in dogs]. AB - The radioactive microsphere technique was used to study quantitatively the blood flow changes after segmental anterior maxillary osteotomy in dog. The results of experiment indicated that the blood flow of gingiva and alveolar bone in segmental side has not significantly changed compared with that of the control side after anterior maxillary osteotomy with intact labial and palatal soft tissue flaps. The blood flow of alveolar bone in segmental side was significantly lower than that of the control side (P < 0.01) when only the labial flap was kept intact, the blood flow of labial and palatal alveolar bone in segmental side was 55.5% and 60.28% lower than that of the control tissue respectively. PMID- 1307952 TI - [The distribution and significance of collagen type III and fibronectin in human gingiva]. AB - Immunohistochemical methods were used to study the distribution and patterns of collagen type III and fibronectin (FN) in human gingiva, their appearance in normal and several periodontal diseases were compared and discussed. It is found that type III collagen and FN are distributed consistently throughout the connective tissue. In inflamed gingiva, both of them are greatly diminished (P < 0.01). It is suggested that they should be in coordination with each other in the maintenance of normal gingiva and the decrease in amount may play a role in the development of periodontal disease. PMID- 1307953 TI - [The research of the lingual flange increasing retentive effect of mandibular complete dentures]. PMID- 1307954 TI - [Determination of contents of glycosaminoglycans in temporomandibular joint discs in dogs]. AB - Glycosaminoglycans (GAGs) are one of the important components of articular cartilage. The present study had determined the contents of uronic acid, galactomine, glucosamine, and hexosamine of temporomandibular joint discs in 10 dogs by Bitter's carbozole reaction method and derivative spectrophotometry. The data indicated that the contents of these components in different bands of the disc are not significantly different and that the discs of dogs contained averagely 0.6%, 0.987%, 0.4% and 1.4% of uronic acid, galactomine, glucosamine, and hexosamine respectively. The data also suggested that the discs contained keratan sulfate and chondroitin sulfate in some degree. This study is significant for analysing TMJ disc functions and its biomechanical properties in the future. PMID- 1307955 TI - [Blood lipid peroxide and superoxide dismutase activity in recurrent oral mucosal ulcer]. PMID- 1307956 TI - [A comprehensive analysis of osteosarcoma, fibrosarcoma and chondrosarcoma of the jaws]. AB - The clinical, pathological and radiographic materials of 99 cases with osteosarcoma, fibrosarcoma and chondrosarcoma of the jaws were analyzed comprehensively. Neither obvious differences of age, sex, duration, location of tumor, clinical symptoms and five-year survivals nor radiographic characteristics were found between these three types of sarcoma. The tumor stage and destruction of cortical bone by the tumor are the important factors influencing the prognosis of the patients. The radiographic findings are valuable for the estimation of prognosis. PMID- 1307957 TI - [Changes in the mandibular growth after ramus osteotomy in rats]. AB - A comparison is made between mandibular growth of the operated side and the unoperated side after vertical ramus osteotomy by measurements of the area and linear distances of bilateral mandibles, and digital image processing technique from the radiographs. The results show that slightly retarded growth of the mandible of the experimental side in growing Wistar rats occurs after osteotomy in the mandibular ramus, but obvious asymmetry is not found Deficiencies of mandibular growth in the operated side are similar in both groups of upward and downward repositioning of the proximal segment. PMID- 1307958 TI - [A computerized system for image cephalometrics]. AB - This system is composed of: (1) a perspective table, (2) TV camera, (3) a high resolution image displayer, (4) a computer, (5) a laser printer The functions of this system are as follows: (1) It can perform cephalometries directly from image of X-ray film, (2) it can diagnose and analyse the deformity and provide treatment plan. This system is valuable for orthodontics and surgical orthodontics. PMID- 1307959 TI - [A preliminary approach of the malocclusion of second permanent molar]. AB - We examined 2183 cases of orodental malocclusion in our clinic. 420 cases of deep overjet of second permanent molar were found. In this paper we discussed the sex and age of the patients, distribution of tooth position, ratio, degree of overjet, causes of malocclusion, malocclusion condition, endangerment, prevention and treatment. PMID- 1307960 TI - [Straight wire appliance in orthodontic practice]. AB - This paper is a preliminary report of using Straight Wire Appliance (SWA) in orthodontic practice in our school since 1989. Thirty finished cases including malocclusion, extraction mode, treatment sequence and time and the outcome, of treatment were analysed. Discussion of the problems concerning arch wire and correction of deep overbite was made. The authors confirm that SWA is a simple and effective type of appliance and it is easily to popularize in orthodontic practice in our country. PMID- 1307961 TI - [Hand wrist ossification and adolescent growth spurt]. PMID- 1307962 TI - [Tip-edge appliance technique]. PMID- 1307964 TI - [The transmission electron microscopic study of the carious dentine]. PMID- 1307963 TI - [The mechanism of topical applied ion supplemented acidulated phosphate fluoride gel effects on dental enamel demineralization: an in vitro study]. AB - The present study was carried out on dental enamel to describe surface changes in the scanning electron microscope and crystallites changes in the high-resolution transmitted electron microscope as related to treatments of topical applied ion supplemented acidulated phosphate fluoride (APFI) gel and artificial caries agent demineralization in vitro, which imitated in vivo with pH- cycling condition. Our data suggest that topical application of APFI gel produce some CaF2 spheres on the surface of enamel and some fluoride-containing apatites in dental enamel. The latter are considered as result of F- and CaHPO4 or hydroxyapatites. The essence of chemical reactions are discussed. The results confirm that enamel treated with APFI gel becomes more resistant to artificial caries agent and electron radiation damage. PMID- 1307965 TI - [Tetrazolium-based colorimetric assay (MTT) and its application in chemosensitivity testing of antitumor Chinese medicine]. PMID- 1307967 TI - [Measurement of the right ventricular systolic pressure in ventricular septal defect--a simultaneous correlative study with Doppler echocardiography and dual cardiac catheterization]. AB - To assess the reliability of Doppler echocardiography (DE) in measuring the right ventricular systolic pressure (RVSP) in ventricular septal defect (VSD), both left and right heart catheterization (Cath) and DE were performed simultaneously in 59 cases with VSD. Systolic shunt velocities through VSD were recorded by DE and converted into the peak instantaneous (delta P-PD) and mid-systolic (delta P MD) pressure gradients using the simplified Bernoulli equation RVSP was estimated by subtracting delta P-PD from the brachial artery systolic pressure (BASP) measured by a cuff sphygmomanometer (method A) and by subtracting delta P-MD from BASP (method B). The left ventricular systolic pressure (LVSP), RVSP, and the peak instantaneous (delta P-PC) and the peak-to-peak (delta P-PP) pressure gradients were measured from pressure c rves. The comparison between BASP and LVSP yielded a good correlation (r = 0.90, SEE = 0.76 kPa). There were also good correlation of interventricular pressure gradients measured by two techniques (r = 0.98, SEE = 0.83-0.93 kPa). Although RVSP estimated by method A correlated well with that measured by Cath, there was a significant underestimation (P < 0.05). On the other hand, RVSP estimated by method B agreed highly with that measured by Cath and there was no significant difference between the two means. We conclude that DE offers a reliable technique for estimating RVSP in VSD noninvasively. PMID- 1307966 TI - [Hemodynamic evaluation of GK and Medtronic-Hall prosthetic mitral valves by exercise Doppler echocardiography]. AB - Hemodynamic alterations were studied in 42 patients with GK and Medtronic-Hall (M H) prosthetic valves by stress Doppler echocardiography after submaximal supine exercise. In the GK group, peak and mean gradients increased from 10.1 +/- 1.7 and 3.4 +/- 1.3 mmHg respectively, at rest to 15.3 +/- 3.1 and 5.4 +/- 1.5 mmHg at peak exercise (mean +/- s), mitral valve area increased from 2.61 +/- 0.34 cm2 at rest to 2.86 +/- 0.45 cm2 at peak exercise (P < 0.05). In the M-H group, peak and mean gradients increased from 11.3 +/- 1.8 and 4.3 +/- 1.0 mmHg respectively, at rest to 15.0 +/- 1.9 and 5.8 +/- 1.5 mmHg at peak exercise. Mitral valve area increased from 2.66 +/- 0.43 cm2 at rest to 2.94 +/- 0.38 cm2 at peak exercise (P < 0.05). The results showed that peak and mean gradients at rest in patients with GK prosthetic valve were lower than those of M-H group. But after exercise, the two prosthetic valves showed similar characteristics in hemodynamics. Exercise Doppler echocardiography is a simple, noninvasive and reliable method for the evaluation of the function of mechanical mitral prostheses. PMID- 1307968 TI - [Evaluating left ventricular diastolic function in coronary heart disease with pulse Doppler echocardiography]. PMID- 1307969 TI - [Dissecting aorta diagnosed by transesophageal echocardiography]. PMID- 1307970 TI - [The effect of indapamide on plasma prostaglandins in hypertensive patients]. AB - After two weeks' treatment of indapamide (2.5 mg/d) in 30 cases of mild to moderate hypertensive patients, there was a significant decline of systolic and diastolic blood pressure. And 8 weeks after indapamide administration, 2/3 of the total treated patients achieved complete control of hypertension. During the treatment period, there were no changes of serum cholesterol, triglyceride and renal function, except a slight, but still in the normal range, decrease of serum potassium and sodium. Concurrently, plasma vasoconstrictive prostaglandins TXB2 (metabolite of TXA2) and PGF2 alpha reduced significantly (P < 0.01 and P < 0.001 respectively), whereas plasma vasodilative prostaglandins 6-keto-PGF1 alpha (metabolite of PGI2) and PGE2 increased significantly (P < 0.02 and P < 0.05 respectively). The results support the theory that prostaglandins system may play an important role in the hypotensive process of indapamide. The influence of indapamide on prostaglandin system may favour the improvement of platelet function and the maintenance of the homeostasis. PMID- 1307971 TI - [Clinical observation on pause-dependent long QT syndrome and torsade de pointes ventricular tachycardia]. AB - Ten patients with long QT syndromes (LQTs) and torsade de pointes (Tdp) were evaluated. The following features were noticed: (1) Serum potassium concentration was reduced in 5 of 10 patients (50.0%, mean value 3.0 mmol/L); (2) The QT interval (mean value 0.50s) was significantly prolonged in all patients; (3) A flat and wide T wave, an abnormal increase in U wave amplitude close to the end or the peak of the T wave and these changes were accentuated by pause or a sudden deceleration in ventricular rhythm; (4) The critical beat of Tdp inevitably started after the peak of the T wave of a markedly prolonged QT interval. Cycle lengths preceding torsade de pointes were shown in a pattern of short cycle-long QT-"late premature ventricular contraction" initiating sequence changes. PMID- 1307972 TI - [Clinical and pathological analysis of sudden coronary death in hospitalized elderly patients]. AB - Forty-five hospitalized elderly patients with coronary heart disease who died suddenly within 6 hours after the onset of symptoms were analyzed clinically and pathologically and summarized as following. (1) All the cases showed abnormal ST segments or T waves on ECG. (2) Various degrees of cardiac dysfunction were found clinically in all the patients. (3) Pathological examination of 31 cases revealed serious coronary atherosclerosis. New myocardial necrosis and/or multiple myocardial scars existed in about two-thirds of the patients. Based on these findings and characteristics, it is speculated that sudden coronary death in the elderly patients is caused by imbalance between oxygen supply and demand in the myocardium or deterioration of the cardiac function, which may result in fatal ventricular arrhythmia. Therefore, the prevention of sudden coronary death in the elderly patients should be focusing on reduction of myocardial ischemia, improvement of myocardial metabolism and protection of cardiac function. PMID- 1307973 TI - [The thrombolytic action of urokinase enhanced by prostaglandin E1 in vitro]. PMID- 1307974 TI - [The clinical relevant factors of the myocardial ischemic threshold]. AB - The myocardial ischemic threshold (heart rate at the onset of ischemia) was assessed in 92 patients with coronary heart disease. The highest myocardial ischemic threshold (HMIT) ranged from 83 to 163 (122 +/- 18) beats/min usually happened during activities at the daytime. The lowest myocardial ischemic threshold (LMIT) ranged from 45 to 115 (82 +/- 17) beats/min usually happened when awaken early morning or asleep at night. The differences were statistically significant (P < 0.01). The mean variability of myocardial ischemic threshold (VMIT) was 30.22% (range from 8.2 to 51.2%). The variability was correlated positively with the number of ischemic episodes, negatively with LMIT, and larger in senior-aged group than in middle-aged group (P < 0.001). The authors suggest that LMIT and VMIT may be related to the severity of coronary lesions, coronary tonus, and the patients' prognosis, etc. PMID- 1307975 TI - [Surgical treatment of trilogy of Fallot]. AB - Two hundred and thirty-four patients with trilogy of Fallot including 102 cases of severe type were operated in our hospital in the last 15 years. Right ventricular outflow patching was done in 117 cases, Devega tricuspid annuloplasty in 7 cases. Total operative mortality rate was 2.6%. The pathological anatomy and the surgical treatment of the severe type cases were discussed. PMID- 1307977 TI - [The effect of captopril on plasma endothelin and calcitonin gene related peptide (CGRP) in patients with acute myocardial infarction]. PMID- 1307976 TI - [The value of CT in diagnosing abdominal aortic aneurysm]. AB - The CT scanning findings in 30 cases of the abdominal aortic aneurysm were analysed. The value of CT in diagnosing and following up of the abdominal aortic aneurysms was discussed. CT is recommended in comparison with other imaging technics. Thin slices and enhancement were made in order to show the relationship between aneurysm and the origin of the renal arteries when suspected. PMID- 1307979 TI - [An ablation experiment on human aortic wall using fibre-optic induced excimer laser]. PMID- 1307978 TI - [Phenotype analysis of mononuclear cells from endomyocardial biopsy specimens in patients with viral myocarditis and dilated cardiomyopathy]. AB - The distribution and phenotype of mononuclear cells from endomyocardial biopsy (EMB) specimens in patients with viral myocarditis (VMC, 25 cases) and dilated cardiomyopathy (DCM, 10 cases) were studied. T-lymphocytes, including T-h/i (T helper/induced) cells in VMC and T-c/s (T-cytotoxic/suppressor) cells in DCM, were predominated in the infiltrating mononuclear cells within these specimens. The morphological relationship between infiltration of T-lymphocytes and pathological changes of myocardium was also observed, but both macrophages and B lymphocytes were absent. PMID- 1307980 TI - [Early afterdepolarization and cesium chloride induced ventricular arrhythmias]. AB - This study is to demonstrate the role of early afterdepolarization (EAD) in the cesium chloride induced long QT interval and ventricular arrhythmias by recording monophasic action potential (MAP) of right ventricular endocardium with contact electrode in 12 closed chest dogs. The results suggested that EAD could produce triggered premature ventricular beats and ventricular tachycardias (VT) in situ. The first ectopic ventricular beat of EAD induced VT usually appears close to the peak of the U wave. Short-long-short interval sequence preceding episodes of VT occurred in 89.6% of VT. PMID- 1307981 TI - [Mitral apparatus in sheep]. PMID- 1307982 TI - [The advances in the research on the intravascular and intracardiac ultrasound imaging techniques]. PMID- 1307983 TI - [Thoracic surgery in Mexico. Various reflections]. PMID- 1307985 TI - [Chronic familial idiopathic neutropenia]. PMID- 1307984 TI - [Lymphoblastic lymphoma in the adult]. AB - We report a series of 57 adults patients with lymphoblastic lymphoma treated at our Institution between 1975 and 1987. Mediastinal involvement was seen in 74% (42 cases); extranodal involvement (not including bone marrow) in 24% (14 cases); stage IV in 84% (48 patients) and leukemic phase in 19% (11 patients). In 15 cases immunologic studies were performed 14 proved to be of T type and the other one lack both T and B markers. Survival and duration of remission was better when the patients were treated with aggressive chemotherapy that included maintenance and central nervous system prophylaxis. In the multivariable analysis we observed that mediastinal mass, attainment of a complete remission and high levels of lactic dehidrogenase were associated with a worse prognosis. We believe that patients with lymphoblastic lymphoma have an aggressive disease and that the treatment should be more aggressive than in other non-Hodgkin's lymphomas, and include central nervous system prophylaxis. PMID- 1307986 TI - [Fever of unknown origin. Presentation of 180 pediatric cases]. AB - Fever of unknown origin (FUO) is a frequent disorder in pediatric age. FUO is defined as the presence of fever over 38.4 centigrades in a patient for more than three weeks in which the etiology remains undetermined. From 30.736 consecutive admittances into our hospital, 180 patients with FUO were detected, and studied in a systematized way and according to a predetermined protocol. FUO was commonly found in children under six years of age. Our patients presented fever from three weeks to six and a half years of evolution; however, in the vast majority of the cases (n = 115) fever had a three weeks course. Several symptoms and physical manifestations other than fever were observed in our patients but they were widely variable and nonspecific. Infectious diseases were the commonest etiological factor encountered; among them, thyroid fever, and urinary tract infections were the most frequent infectious disorder found; in four children fever was associated to ampicillin administration; in 19 patients, fever was no demonstrated. A large number of laboratory investigations were done in the diagnosis of neoplastic diseases. We think that the study of a patient with FUO requires of a systematized approach. PMID- 1307987 TI - [Fever of unknown origin. A study of cases seen at the third level]. AB - Clinical records of 160 patients admitted with fever of unclear origin were reviewed. Of them, all cases with fever of obscure origin (FOO) were selected based on the following criteria: at least two weeks with fever, with an oral temperature of 37.5 degrees C or more during hospitalization and whose clinical history, physical examination, hemocytologic data, erithrosedimentation rate, urinalysis, febrile tests, glutamic-piruvic transaminase, chest and abdomen radiographies were not suggestive of any specific diagnosis. 32 cases of FOO were found, but only the 30 which had been studied previously in another hospital were considered for analysis. Of these 30 patients, 18 were men and 12 women, with a mean age of 36.3 (range 19-64). Infectious diseases caused 40 percent and neoplastic disease 27 percent of cases. The single most frequent cause was non Hodgkin lymphoma in four cases, followed by tuberculosis and Hodgkin's disease in three patients each. In four cases the cause of fever was not identified. Eleven patients required exploratory laparotomy; in nine of them it was usefull for diagnosis. Our results show a high proportion of neoplastic diseases, probably related with patient's selection and with intrinsic diagnostic difficulty of these kind of diseases. PMID- 1307988 TI - [Necrosectomy and retroperitoneal lavage in necrotic pancreatitis]. AB - Necrotic pancreatitis is the most severe of all acute pancreatitis and treatment with various surgical procedures has had a high mortality. A retrospective study of 37 patients treated by necrosectomy and postoperative lavage-drainage from January 1987 to December 1990 was made. The most frequent etiologies were alcoholic (21 patients) and biliary (15 patients). Eight patients had moderate pancreatitis according to Ranson's classification when they entered the hospital (one died) and in 28 it was severe (eight died). The mean time between entrance to the hospital and surgery was 15.1 days. Twenty five were reoperated, twelve for residual abscesses and eight of these died. The mean hospitalization time was 56.7 (+/- 32.8) days and overall mortality was 24.3%, smaller than that observed in our hospital with other various procedures. It is concluded that necrosectomy and lavage-drainage is a good surgical alternative for patients with necrotic pancreatitis. PMID- 1307989 TI - [Histamine as modulator of potassium currents in ventricular cells isolated from heart of guinea pig. A possible regulator effect of ventricular electric activity]. AB - Histamine is present in cardiac tissues in considerable amount, but its physiological role is not well understood. There are two kinds of histamine receptors on the cardiac cells (H1 and H2). Whereas the H2 actions are very well studied little is known about H1 effects. It has been reported that stimulation of H1 receptors induce a shortening of the action potential as a decrease in excitability, but the ionic mechanisms responsible for these are not known. The aim of the present paper is to explore the possible ionic mechanisms related to these effects on isolated ventricular myocytes by means of voltage clamp technique. Histamine induced a shift in the current-voltage relationship of the potassium background current to the right. This shift implies an increase in outward current at the plateau level, responsible for the shortening, as well as for the decrease in excitability. This is, as far as we know, the first report in potassium background channel modulation by an endogenous substance and firmly support the hypothesis that histamine is playing a role in cardiac modulation. PMID- 1307990 TI - [Increase in neuroendocrine secretion granules in submaxillary and parotid glands in patients with non-insulin dependent diabetes mellitus]. AB - The amount of neuroendocrine granules in microgranular cells of salivary glands were investigated in necropsies of 20 non-insulin dependent diabetics (NIDDM) and in 20 non-diabetic subjects with Grimelius and Fontana-Masson stainings. Granules in serous acini, and intercalated ducts were observed in both groups; however, a significant higher number of granules and microgranular cells were observed in NIDDM subjects as compared with non-diabetics. Both parotid and submaxillary glands were significantly heavier in NIDDM than in the non-diabetic group. These granules may be related to immunoreactive glucagon which has been found in submaxillary glands of rodents and might play a role in the pathogenesis of NIDDM. Further investigations should be performed to clarify whether these cells are the site of glucagon synthesis and also clarify the pathogenesis of NIDDM. PMID- 1307991 TI - [Pancreatic beta cells and cytokines]. AB - Over the past decade the study of Interleukins and Interferons has advanced from functional descriptions to detailed structural understanding. The ability of these growth factors to act, directly or through immune mechanisms on the pancreatic beta-cell and to affect in vitro and in vivo both its morphology and physiology, indicate that they may play a role in the pathogenesis and prevention of insulin-dependent diabetes mellitus. Also, the relation between these cytokines-constitutive or upon stimulation maybe useful to predict the development of diabetes mellitus. PMID- 1307992 TI - [Preservation of the pancreas for the simultaneous transplantation of kidney pancreas]. AB - This paper studies the advances that have participated in the development of preservation solutions for the combined kidney-pancreas transplantation. These developments have been associated most importantly with hypothermia, the use of colloid solutions with high oncotic pressure, and the maintenance of near intracellular ionic concentration. At the present time, the more effective solutions are the plasma-like modified Silica Gel Fraction and the starch and lactobionate based solution such as, the UW. Further advances in this area, would allow for improved results in the combined kidney-pancreas transplant preparation. PMID- 1307993 TI - [Extracorporeal shockwave lithotripsy (ESWL), a non-invasive therapeutic approach in the treatment of urinary calculi]. PMID- 1307994 TI - [Evaluation of nopal capsules in diabetes mellitus]. AB - To find out if commercial capsules with dried nopal (prickle-pear cactus, Opuntia ficus indica may have a role in the management of diabetes mellitus, three experiments were performed: 30 capsules where given in fasting condition to 10 diabetic subjects and serum glucose was measured through out 3 hours; a control test was performed with 30 placebo capsules. OGTT with previous intake of 30 nopal or placebo capsules was performed in ten healthy individuals. In a crossover and single blinded study 14 diabetic patients withdrew the oral hypoglycemic treatment and received 10 nopal or placebo capsules t.i.d. during one week; serum glucose, cholesterol and tryglycerides levels were measured before and after each one-week period. Five healthy subjects were also studied in the same fashion. Opuntia capsules did not show acute hypoglycemic effect and did not influence OGTT. In diabetic patients serum glucose, cholesterol and tryglycerides levels did not change with Opuntia, but they increased with placebo (P < 0.01 glucose and cholesterol, P = NS triglycerides). In healthy individuals glycemia did not change with nopal, while cholesterol and triglycerides decreased (P < 0.01 vs. placebo). The intake of 30 Opuntia capsules daily in patients with diabetes mellitus had a discrete beneficial effect on glucose and cholesterol. However this dose is unpractical and at present it is not recommended in the management of diabetes mellitus. PMID- 1307995 TI - [Corneal autograft, an additional alternative in corneal transplantation]. AB - Corneal autotransplantation is a process in practice for various years. This procedure has the advantage of providing corneal tissue which will not be immunologically rejected in the host. This paper reports five cases in which this procedure was undertaken by changing a transparent cornea from a blind eye on the other side. PMID- 1307997 TI - [Transluminal angioplasty of the coronaries or intraluminal coronary surgery]. PMID- 1307996 TI - [Mitral valvuloplasty]. PMID- 1307998 TI - [Growth hormone]. PMID- 1307999 TI - [Improvement in the quality of medical care]. AB - The object of this research was investigating the existence of programs, as well as the patient's and healthy worker's opinions, concerning the quality of Medical Attention in the representative medical institutions in Mexico City (Distrito Federal). Eighteen directors of medical institutions were interviewed; as well as fifty university graduates, one hundred out patients from health centers and three hundred patients treated at general hospitals. A poll was applied to two hundred and fifty physicians and two hundred and fifty nurses from health centers and general hospitals. RESULTS: The eighteen institutions studied had permanent programs for Supervision and assemend. Other activities were also detected: sixteen had Technical Committees, five had a Department for Complaints, three had Quality Circles, two had programs for Evaluation of Educational Needs, two had Patients Polls, two had Worker's Polls, one had a Shadow Study and two had Quality Control Programs. The 86% of university graduates belonged to the social security system. Among these, 36% attended public services, 36% of them did this selectively and 28% did not use social security. 30% felt that public medical services were good, 14% less than good and 56% bad. 36% felt that public services were better than private ones, 36% said both were equally good and 28% judged the public system as worse than the private ones. The main deficiency reported was a lack of personal warmth. The patients from both the general practice and hospitalization graded the opportunity, warmth and process of medical attention as variables with figures of 80% or more. The frequency of diverse "complications" was 66% in out patients and 36% in the hospitalized ones. The physicians and nurses graded the infrastructure, teaching, laboral motivation and satisfaction, and continuity of services as variables with percentages of 50% to 60%; whereas the variables of warmth, control and supervision with values of 60% to 80%. Hospital nurses were less satisfied. These results show patients to have an acceptable satisfaction whereas the health personnel was unmotivated. Practical actions are suggested to improve the quality of medical attention. PMID- 1308000 TI - [Epidemiology of mycetoma in Mexico: study of 2105 cases]. AB - A survey was carried out in Mexico to determine the incidence and epidemiological characteristics of mycetoma. Data was collected from a total of 2105 cases of mycetoma throughout a 30 year period (1956-1985), with an average incidence of 70 cases per year. Results showed a sex distribution of 76.1% male and 23.9% females. Age distribution indicated a 35% between 16 to 30 and 23% between 31 to 40 year old population. Most cases occurred in land-workers (60.2%) and in housewives with rural residence (21.3%). Lesions occurred most frequently in lower limbs (64.1%), trunk (17.4%) and upper limbs (13.6%). The geographic distribution within Mexico revealed that the States with the highest incidence were: Jalisco, Nuevo Leon, San Luis Potosi, Morelos and Guerrero The predominant etiologic agents found 97.8% corresponded to actinomycetes, from which Nocardia brasiliensis (86.6%) and Actinomadura madurae (10.2%) showed the higher frequency. Eumycetoma (2.2%) was due to Madurella grisea and M. mycetomatis in most cases. PMID- 1308001 TI - [The price of health]. PMID- 1308002 TI - Antigenic and genomic differences of two Jasper strains of infectious pancreatic necrosis virus. AB - Strains of infectious pancreatic necrosis virus (IPNV-Jasper) obtained from two different laboratories were compared serologically with polyclonal and monoclonal antibodies. Nucleotide sequence and restriction endonuclease patterns of 359-bp fragment of genome segment A cDNA were also compared. Substantial differences were found in both analyses that will support the fact that the two Jasper strains are not identical. PMID- 1308003 TI - Inefficient transmission of HTLV-I to MOLT-4 cells by cell-free virus and cocultivation. AB - Transmission of human T cell leukemia virus type I (HTLV-I) to a T cell line (MOLT-4#8) was studied using cell-free virus infection or cocultivation with an HTLV-I-transformed T cell line (MT-2). Immunofluorescence and FACS analyses showed that HTLV-I was efficiently adsorbed onto MOLT-4#8 cells. However, after adsorption, no extrachromosomal viral DNA in the cells was detected by the Southern blot method. In contrast, when MT-2 cells were cocultured with MOLT-4#8 cells, generation of extrachromosomal DNA was clearly observed. These data suggest that the cell-free HTLV-I may have difficulties in penetration, uncoating or reverse transcription. After cocultivation, MOLT-4#8 cells chronically infected with HTLV-I were cloned and analyzed. Only four provirus-positive cell lines were obtained. The transmission rate of the virus by cocultivation seemed to be low in our experimental system, although marked cell fusion was observed. Moreover, none of the cloned cell lines which harbored HTLV-I provirus expressed any viral protein. Inefficient integration and expression of the provirus might be hypothesized as compared with human immunodeficiency virus type 1 transmission. PMID- 1308004 TI - Bacterial luciferase produced with rapid-screening baculovirus vectors is a sensitive reporter for infection of insect cells and larvae. AB - Bacterial luciferase, derived from a fusion of the luxA and luxB genes of Vibrio harveyi, has been expressed at very high levels in caterpillars and insect cells. The coding sequence for luciferase was inserted into vectors developed in our laboratory which were designed to expedite screening of recombinant virus. These vectors contained the beta-galactosidase indicator gene under control of immediate early (IE1), early (ETL), or very late (P10) promoters and a cloning site for inserting the fused luciferase gene next to the polyhedrin promoter. Recombinant baculoviruses containing the luciferase gene as well as the beta galactosidase gene could be easily selected when Bluo-gal (beta-galactosidase indicator) was included in the plaque assays. Using cells derived from the fall armyworm (Spodoptera frugiperda), luciferase was strongly expressed very late in infection (48-72 h). The bacterial luciferase assay was sufficiently sensitive that light production could be detected from an extract of a single cell. In addition, live insects, including the cabbage looper (Trichoplusia ni) and saltmarsh caterpillar (Estigmene acrea) were infected by mixing recombinant baculovirus into their diet. Cabbage loopers (with an average wet weight of 223 mg) produced at least 195 micrograms of active luciferase and levels of synthesis peaked between 96-120 h. The results indicate that bacterial luciferase may be used as a reporter of gene expression in insects. PMID- 1308005 TI - Making the family center the world of the special needs child. PMID- 1308006 TI - Parent consultants in the health-care system: a new approach in the care of children with special needs. AB - A unique and innovative role for parents has emerged from the recent emphasis on family-centered, community-based health care for children with special health care needs. The role of parent consultant is described in the following article. Identified are the characteristics of the consultant role, benefits as well as challenges, how the role is enacted, and ways to finance the position. Nurses can serve to support and nurture the parent consultant role to ensure positive role development. Parent consultants have a unique and important perspective to offer in the delivery of a family-centered approach. PMID- 1308007 TI - Advisory committees for agencies that provide services for children with special health-care needs. AB - The Children's Special Health Care Services Advisory Committee is an advisory group that includes stakeholders in the delivery of care for children with special health-care needs. An emphasis has purposely been placed on consumer participation to ensure adequate voice and balance with other provider, legislative, and bureaucratic interests. The Advisory Committee has assumed an aggressive and complete role in reviewing and recommending every aspect of the program. As a result of this active co-ownership, the program has repeatedly survived threats of serious budget cuts and reductions to its base. Agreement between providers and consumers on values, structure, and operational needs has been reached. A win-win approach has been possible, not only in the planning and growth of the program but also in the policy arena, legislatively, and with the administration. PMID- 1308008 TI - Care management for children who are medically fragile/technology-dependent. AB - Care management is a nursing role that has received more attention over the past decade as the number of children with special health-care needs has increased. The particular role of the specialized care manager within the Michigan Department of Public Health is described in the following article. The purpose is to highlight how the role emerged from a philosophy of care and how families receive the care management services. Future challenges for the state-supported role of care manager are described. PMID- 1308009 TI - Establishment of a state-supported, specialized home care program for children with complex health-care needs. AB - Establishment of a systematic approach to home care for children who require complex, technology-dependent care requires a well-thought-out process of collaboration and planning between all parties involved--the family, the professional, and the hospital. The State of Michigan Department of Public Health elected to assist families in taking their children home through a Specialized Home Care Program funded by combined sources that emphasized child care needs first rather than cost savings. This review identifies the development of roles, processes and products, and methods to enhance the discharge planning and home care processes. These processes indicate the need for parent involvement and teamwork with health-care professionals. Refinement of the program is suggested as well as further development of an evaluation component and family assessment tools. PMID- 1308010 TI - Diastolic dysfunction of the heart, and its importance. PMID- 1308012 TI - Comparative immunogenicity of different hepatitis B vaccines among certain high risk groups in India. AB - The immunogenicity of three different commercially available, well established Hepatitis B vaccines was determined. Three groups of high risk individuals were administered the vaccine, viz, Albugam (20 micrograms), Engerix-B (20 micrograms) and vaccine produced by Cheil Sugar & Co. (3 micrograms) respectively in a schedule of 3 doses as recommended by the manufacturers. A fourth group was administered a combination of the Albugam (2 doses) and Engerix-B (1 dose) vaccine. The sera collected 2 months after the 3rd dose showed seroconversion rates to be 100 percent and 95.34 percent respectively in the group which received the Albugam and Engerix-B vaccines respectively. The group which received a combination of both, the seropositivity rate was also 100 percent. The Chiel Sugar vaccine gave a seroresponse of only 52.38 percent. Geometric mean titres among the groups which received Albugam vaccine (501.30) were comparable to those receiving the combination of Engerix-B and Albugam (442.28). Those who received all 3 doses of Engerix-B vaccine showed a significantly lower GMT as compared to the above tow groups (GMT--43.14, p < .001, P < .001 respectively). The GMT in the group that received Cheil Sugar Vaccine was 3.81. Seroresponse was found to be inversely proportionate to age. PMID- 1308011 TI - Haematological and coagulation profile in acute falciparum malaria. AB - The haematological and coagulation profile of 30 cases of acute falciparum malaria were studied. Anaemia, mostly normocytic, normochromic, was observed in 86.7% of cases majority of whom had complications. Severe anaemia (HB < 6gm.) observed in 10% of cases was associated with 100% mortality. Leucocytosis and leucopenia were observed in 13.3% and 6.6% of cases respectively. 90% of cases had thrombocytopenia, the lowest count recorded being 26,000/- cmm. 16.7% of cases had evidence of intravascular coagulation but manifested as generalised bleeding in only one case. Bone marrow aspiration done in 10 cases revealed no abnormality, except for falciparum parasites observed in 2 cases. PMID- 1308013 TI - Air pollution related respiratory morbidity in central and north-eastern Bombay. AB - A study of 4 comparable communities in central & northeastern Bombay (2 each) among randomly matched 349 subjects in 1988-9, along with ambient sulfur dioxide (SO2), Nitrogen dioxide (NO2) & suspended particulate matter (SPM) air monitoring was carried out. The levels in winter were higher particularly for SO2 in Parel (upto 584 micrograms) in Maravali; Deonar showed lower pollution. There were inter-area differences for housing, income, residential history but age-sex differences were small; these were reduced by matching. Clinical respiratory symptoms were higher in Parel & Maravali (cough 12% and 11.2%, dyspnoea 17% & 13.3% respectively). Cardiac problems are commoner in Parel (11.0%). Smoker had cough more often but not dyspnoea. Maravali had a high prevalence for headache and eye irritation (9.5%). Those using kerosene suffered more than those using gas (22.2% as compared to 9.2%) Lung functions (FVC, FEVI) were lowest in Parel for males and in Maravali for females. Expiratory flow rates were lower at Dadar and then at Maravali. Despite lower SO2 pollution, Maravali residents suffered equally as in Parel. This may be due to added effect of diesel exhausts (NO2, SPM) or other unmeasured chemicals. PMID- 1308014 TI - Wegener's granulomatosis in northern India. AB - Till recently, Wegener's granulomatosis (WG) was considered a rare disease in India. Over the last 5 years we studied 13 proven cases of WG. This paper describes the details of the disease as seen in these patients, and response to corticosteroid and cyclophosphamide therapy, and compares these observations with a Western and an Indian study. PMID- 1308015 TI - Wegener's granulomatosis: clinical experience with eighteen patients. AB - Wegener's granulomatosis is being recognised with increasing frequency in India. Our 18, histologically confirmed, patients had a clinical profile similar to that described from developed countries. Delayed diagnosis led to the death of nine patients, usually within days of hospital admission, due to extensive vasculitis and renal failure. Tuberculosis was the most frequently considered diagnosis and 12 patients had been treated for it in spite of progressive clinical deterioration. Those who could be adequately treated with low dose daily cyclophosphamide and corticosteroids did well. Six of seven such patients are alive and well 1-8 years later. We believe that if prompt lung biopsy and ANCA determination are resorted to in patients with "resistant tuberculosis", it will greatly expedite case detection, diagnosis and optimum treatment of this remediable disease. PMID- 1308016 TI - Cerebrovascular manifestations of neurosyphilis. PMID- 1308017 TI - Diuretic induced hyponatraemia in the elderly. AB - Diuretics are an important cause of symptomatic hyponatraemia in the elderly. The hyponatraemia is often associated with hypokalaemia which may play a role in the aetiology. Diuretic induced hyponatraemia must be considered in the differential diagnosis of elderly patients presenting with altered sensorium or seizures. This is especially important in those known to be hypertensives since diuretics are frequently used to treat hypertension in the elderly. PMID- 1308018 TI - Amyloidosis complicating psoriatic arthropathy. PMID- 1308019 TI - Dystrophin test in differential diagnosis of childhood muscular dystrophies. AB - Two cases of childhood muscular dystrophy are described. One of them had clinical features suggestive of Emery-Dreifuss muscular dystrophy and the other with some features of Prader-Willi syndrome, besides proximal muscle weakness. Muscle biopsy from both cases revealed a clear abnormality of dystrophin, and were diagnosed as having Duchenne muscular dystrophy (DMD) by immunofluorescence examination; that is, absent dystrophin at the membrane of the muscle fibers. The clinical spectrum of DMD-related myopathies and the importance of dystrophin testing in childhood muscular dystrophies is discussed. PMID- 1308020 TI - Double orifice mitral valve: report of 4 cases. AB - Double Orifice Mitral Valve (DOMV) is a rare congenital abnormality. Reports of 4 patients with DOMV are presented. As associated anomalies, one had ostium primum atrial septal defect (ASD). Second one had Ebstein's anomaly. Third one had grade IV tricuspid regurgitation, thickened tricuspid valve and right atrial mass. Fourth one had sinus venosus ASD. Echocardiography is the gold standard investigation. Surgical treatment depends upon the mitral valve function and associated anomalies. PMID- 1308022 TI - Fluorescein angiography in systemic hypertension. AB - This study evaluates the role of fluorescein angiography (FA) in detecting changes in the retinal and choroidal capillary bed in hypertension and defines its advantages over direct ophthalmoscopy. 37 patients with varying degree of severity of hypertension were studied. Direct ophthalmoscopy and FA was done in all cases. No significant difference was found in documenting vessel calibre and arteriovenous crossing changes with either of the methods. Hard exudates were not visualized on FA. Capillary bed and choroidal abnormalities could be better studied on FA which can be employed in selected patients of hypertension but its use is not advocated as a routine in all hypertensives. PMID- 1308021 TI - Multiple meningiomas. AB - True "multiple meningiomas" as defined by Cushing are rare. A case of multiple meningiomas without stigmata of neurofibromatosis, in a 53 year old man, treated surgically is reported. The relevant literature on multiple meningiomas has been reviewed. PMID- 1308023 TI - Biochemical assessment of cholelithiasis. AB - Bile and serum were analysed in 45 cases of cholelithiasis and 25 control subjects for cholesterol, phospholipids, bilirubin, alkaline phosphatase and LCAT activity. Serum phospholipids were found to be elevated in sixty percent of cases, whereas phospholipids in bile were found to be decreased. Serum alkaline phosphatase and alanine aminotransferase were normal. Serum and bile LCAT activity was found to be significantly depressed. PMID- 1308024 TI - Publication lag intervals--a reason for authors'apathy? PMID- 1308025 TI - Quantitative estimation of urinary protein excretion by refractometry. AB - Quantitative estimation of proteinuria done by the refractometric method was compared with that done by the sulphosalycilic acid method and biuret method in 102 urine samples. The analysis of results by students' t test showed no statistically significant difference between the three methods. It is concluded that quantitative estimation of urinary protein excretion by refractometric method is a simple cheap and reliable method and can be performed easily in the outpatient clinic. The instrument is quite handy and can be carried in the pocket. PMID- 1308026 TI - Circadian variation in the onset of pain of acute myocardial infarction in Indian patients. AB - Two hundred patients admitted with acute myocardial infarction (AMI) to the coronary care unit of a tertiary-care-teaching hospital over a period of 1.5 years were studied prospectively, with regard to the time of onset of pain of infarction. The maximum number of infarctions (i.e. 71) (35.6%) occurred between 4.00 AM and 10.00 AM, significantly higher than other 6 hour periods of the day (P < 0.01). Various possible mechanisms leading to this early morning increase in the incidence of AMI and its therapeutic implications are discussed. PMID- 1308027 TI - Rare poisoning with cerebra thevetia (yellow oleander). Review of 13 cases of suicidal attempt. AB - Clinical presentation, course and management of thirteen patients of suicidal poisoning with seeds of yellow-oleander were studied. All patients who took more than two seeds had gastro-intestinal as well as cardiovascular toxic effects. Patients responded well to symptomatic and supportive treatment when they had four or less than four seeds and reported to hospital within four hours intake. Progress was bad when patients took more than four seeds and reported after four hours of intake, cause of death in all the patients was cardiogenic shock. PMID- 1308028 TI - Prognostic significance of reciprocal changes in acute myocardial infarction. AB - Study on 108 patients of acute myocardial infarction has shown the incidence of reciprocal ST depression in ECG in 58.3% patients. Those showing reciprocal changes had higher (65.0% Vs 15.5%) incidence of complication such as dysrhythmias, conduction disorders. hypotension, left ventricular failure or CCF which was more conspicuous in inferior myocardial infarction. There was higher incidence of complications (74.4% vs 18.7%) whenever ST depression was 2 mm or more (P < 0.001) and there was steep rise in complications whenever the ST depression persisted for 2 days and beyond. PMID- 1308029 TI - Persistent neutrophilic meningitis. An unusual presentation of tuberculous meningitis. PMID- 1308030 TI - Falling standard of examinations in the medical sciences. AB - Despite the strictly specified criteria laid down by the Medical Council of India the standard of examinations in the medical sciences in the country is continuously falling. This is mostly because of lack of sincerity and integrity of many examiners. This is an unwelcome situation and requires serious thought and appropriate urgent remedy. PMID- 1308031 TI - Diabetic peripheral neuropathy. PMID- 1308032 TI - Tetracycline resistant El Tor Vibrios in Loni area. PMID- 1308033 TI - Multi resistant Salmonella typhi from rural southern Maharashtra. PMID- 1308034 TI - Poem syndrome. PMID- 1308036 TI - Plasmodiasis. PMID- 1308035 TI - Diabetic peripheral neuropathy. PMID- 1308037 TI - The new genetics and its application in the study of childhood muscular dystrophies. PMID- 1308038 TI - Approach to tuberculosis of the bone marrow. PMID- 1308039 TI - Intravenous administration of metallic mercury with homicidal intent. PMID- 1308040 TI - Pneumocystis carinii pneumonia (PCP) in a renal transplant recipient in India. PMID- 1308041 TI - Portable blood glucose monitoring devices. PMID- 1308042 TI - Astemizole--induced paresthesiae. PMID- 1308043 TI - Myocardial bridge: an enigma. PMID- 1308044 TI - Hormones and bioactive substances in milk: a rudiment or a message? AB - The composition of milk is the result of an evolutionary process with both positive and negative natural selection mechanisms where variants with components supporting offspring development from birth to reproduction (but not later) are preferred. Almost all known hormones and many other bioactive substances are present in milk of various species. Some of them are synthesized by the mammary gland, the others are passively or selectively transported (and eventually modified) from blood into milk. Hormones in milk are of importance for the regulation of the functions of the mammary gland itself. There are indications that they affect (sometimes permanently) both functions of suckling GIT and other functions after their resorption during the defined developmental periods. The definite role of these messages for further offspring development remains to be established. PMID- 1308045 TI - Magnesium deficiency impairs rat soleus muscle glucose utilization and insulin sensitivity. AB - Insulin resistance (IR), probably a common pathway of atherosclerosis development in various diseases, was suggested to be related to magnesium (Mg) deficiency. The in vivo observations required an in vitro extension. The study was performed on isolated rat soleus muscle incubated in Ringer bicarbonate with/without Mg. Mg deficiency inhibited basal, insulin- and tolbutamide-stimulated glucose utilization. Insulin-stimulated glucose utilization was inhibited even in the case that insulin was given to rats before sacrifice. Similar inhibition of glucose utilization was found in Ca deficiency and the simultaneous lack of Mg had no additive effect. It is concluded that Mg deficiency inhibits glucose utilization at the level of Ca mediation of glucose transport regulation. PMID- 1308046 TI - Antioxidant systems--physiology and pharmacotherapy trends. AB - Metabolic processes connected with the effects of oxidation and antioxidation with participation of cellular energy are presented and therapeutic possibilities connected with coenzyme Q and N-acetylcysteine are discussed. PMID- 1308047 TI - The effect of a cholecystokinin receptor antagonist lorglumid on the proteinase antiproteinase balance in taurocholate acute experimental pancreatitis (AEP) in rats. AB - The effect of new CCK receptor antagonist, lorglumid on taurocholate AEP in rats was studied. Lorglumid was applied intraperitoneally at a dose of 5.6 mg/kg BW immediately after taurocholate injection into choledochopancreatic duct. Activity of amylase, antithrombin III (AT III), alpha 1 protease inhibitor (alpha 1 PI), alpha 2 antiplasmin (alpha 2 AP) and alpha 2 M) in plasma, trypsin and chymotrypsin in pancreata were measured after 1, 3, 6 h of AEP. In AEP treated by lorglumid serum amylase activity and pancreatic wet weight was significantly reduced. The use of lorglumid prevented the increase of alpha 1 PI and alpha 2 AP compared to not treated animals. AT III and alpha 2 M in plasma and trypsin and chymotrypsin activity in pancreata did not change significantly in all groups. The mortality of the lorglumid treated rats was significantly lower in comparison with control group. It is concluded that lorglumid in taurocholate AEP moderates the changed plasma proteinase-antiproteinase balance. Our results indicate a protective effect of lorglumid in this model of acute experimental pancreatitis. PMID- 1308048 TI - Helicobacter pylori in experimental acute and chronic gastric and duodenal ulcer in Buffalo [correction of Bufallo] rats. AB - The experiment was performed using inbred Buffalo rats to confirm the coincidence between peptic, gastric and duodenal ulcer and Helicobacter pylori infection. The results suggest an unquestionable meaning of Helicobacter pylori appeared to be as strong ulcerogenic factor in rats as ligation of pylorus and diffusely administrated histamine. PMID- 1308049 TI - Long-term antiarrhythmic pharmaco-therapy guided by Holter monitoring in patients with malignant ventricular arrhythmias and ischemic heart disease. AB - In 126 patients with clinical ventricular tachycardia and/or fibrillation, ischemic heart disease and repetitive and/or frequent ventricular ectopic beats long-term therapy guided by Holter ecg was assessed. Criteria for efficacy of antiarrhythmic drugs were following: 1) > 75% decrease in ectopic beats, 2) elimination of salvos, 3) > 90% reduction of couples and R/T and 4) reduction of multiformity up to 2 forms. They were fulfilled in 71% of patients (responders). During follow-up 1-49 months, mean 20, rate of sudden death was lower in responders as compared with nonresponders (p < 0.05). However, suppression of ventricular ectopic beats was not predictive for a favorable outcome, because the incidence of arrhythmic events and total cardiac death was similar in the two groups. PMID- 1308050 TI - Interactions between atrial natriuretic factor and vasopressin. PMID- 1308051 TI - Protective action of vitamin E on the subcellular structures of lymphocytes intoxicated with pesticides in vitro. AB - Vitamin E was used as a protection for human lymphocytes in vitro against the toxic effects of dichlorvos, an organic phosphate pesticide. As the markers of the toxic changes in the lymphocytes lysosomes were chosen as a membrane structure, and nucleoli as a structure connected with protein synthesis. The obtained results were compared with the effects obtained previously in analogous studies after intoxication of lymphocytes with lindan and fenarimol. The experiment showed that vitamin E protected the lysosomal membranes more effectively than the nucleolar structure in these cells. PMID- 1308052 TI - Prostaglandins during haemodialysis treatment. AB - The prostaglandins 6-keto Pgf1 alpha,PG F2 alpha and thromboxane B2 before and during haemodialysis were studied by means of radioisotope method. A significant increase of 6-keto PGF1 alpha and decrease of PGF2 alpha was found. The concentration of thromboxane B2 was markedly, but not significantly decreased. This constellation inhibiting the thrombocytes aggregation and promoting vasodilation seems to be favourable as far as biocompatibility is concerned. Dialysis treatment caused no significant changes in prostaglandins concentration. PMID- 1308053 TI - A study of circadian rhythms of estriol secretion in the third trimester of gestation complicated by gestosis and intra-uterine growth retardation (IUGR). AB - The circadian changes in serum estriol concentration in the case of gestosis (at 30-36 weeks gestation) and intra-uterine growth retardation-IUGR (at 28-36 weeks) were examined. The control group consisted of pregnant patients without placental insufficiency at 26-34 weeks gestation. No circadian rhythms of estriol secretion was found in patients with gestosis and IUGR, whereas such a rhythm was confirmed in normal pregnancies. The evaluation of circadian changes in estriol concentration in the third trimester of gestation may be useful when diagnosing chronic placenta insufficiency. PMID- 1308055 TI - New perspectives and hope for cure-reflecting recent genetic developments in cystic fibrosis. AB - The isolation of cystic fibrosis gene at the CF locus assigned to the long arm of chromosome 7 band q31 and definition of its protein product named CFTR (cystic fibrosis transmembrane conductance regulator) permits to understand the basic defect in this inherited disorder known as cystic fibrosis (CF) or mucoviscidosis. A variety of mutations of CF gene was revealed and the most common, a deletion of the 3 nucleotides that encode phenylalanine (Delta F508) with the variable incidence among the different ethnic groups of CF patients was delineated. CF is a variable disease and genetic testing can be useful to explain this variation but to date the phenotype-genotype correlation is not clarified. Polymerase chain reaction (PCR) amplification is used to test CF gene in CF patients and their families but is not sufficiently genetically informative to population screening for carrier detections. Recently identified glycoprotein encoded by CF gene is responsible for the regulation of the membrane chloride channel of epithelial cells and the experiments used retro-virus-mediated gene transfer demonstrated complementation CF defect in vitro. The way for gene therapy in this disease is open. An alternative approach to use the germ line cells to CF gene therapy is prerequisite of the development of the preimplantation preconception genetic CF diagnosis. The researchers managed already to express human CFTR gene in vivo in cotton rats lungs through the viral delivery system. It will be generalized into the airways of CF patients with hope that normal CFTR will reverse the physiological defect in CF cells. PMID- 1308054 TI - The alteration on serum thyroid hormones and iodine levels when the 10% povidone iodine solution was topically performed on ano-rectal mucosa. AB - In this experiment, the 10% povidone-iodine (PI) solution was topically administered on ano-rectal mucosa by enema and its effects on thyroid hormones and iodine levels in serum were examined in rabbits. The solution was given in a volume of 20 ml daily for three days. Blood samples were drawn at 1st, 4th and 7th days after the first enema. The serum iodine levels reached maximum values at the first day was still elevated at the 4th and 7th days, but T3, T4 and TSH values remained within the normal limits. Iodine did not produce alterations in the levels of thyroid hormones and TSH, although it is known that a considerable amount of it is absorbed from the intestinal lumen. PMID- 1308056 TI - Evaluation of blood coagulation tests in deep venous thrombosis. AB - On the basis of the hemocoagulation and hemostasis parameters study the actual hemostasis state was evaluated in 30 patients treated for active deep venous thrombosis (DVT) in dependence on its extent. In comparison with 30 healthy persons there were found statistically significant changes in a majority of laboratory parameters that can indicate thrombophilic state. Platelet activation, increased coagulation system activity, decreased fibrinolytic activity as well as increased fibrinogen and fibrin degradation products were demonstrated. The positive correlation between the extent of DVT and the relevance of hemostasis changes was revealed which results to these conclusions: the more extensive DVT- the more intensive tendency to thrombophilia up to intravascular blood coagulation activation was observed. Although the adequate prolongation of the prothrombin time (during the coumarin therapy) or APTT (during the heparin therapy) was achieved, the laboratory parameters showed a therapy insufficiency. In the cases of laboratory signs of the activated intravascular blood coagulation we can recommended a fortification of the oral anticoagulant therapy by its combination with antiplatelet drugs or by its temporary replacement by the heparin therapy. PMID- 1308057 TI - Albumin and packed red blood cells in the treatment of severely isoimmunised pregnancies. AB - The most effective method of treatment of severe cases of fetal haemolytic disease are intrauterine intravascular transfusions. In some hydroptic cases however, the administration of only packed red blood cells produces unsuccessful results. We found that albumin supplementation paralleled with PRBC injection significantly increases the effectiveness of intravascular treatment. PMID- 1308058 TI - The effect of cytotoxic drugs on the development of murine granulocyte-macrophage (GM) progenitor cells. AB - The effect of cytotoxic drugs was tested on the hematopoietic system by assay of the ability of granulocyte-macrophage colony forming cell (GM-CFC) in mice to create GM colonies. The in vivo ability of bone marrow progenitor cells to granulocyte-macrophage colony formation, was tested after long-term peritoneal cytotoxic drug administration. The direct effect of these agents on cells in vitro culture was evaluated also. It was found that cytotoxic drugs inhibit the GM colony formation. The degree of damage to the bone marrow progenitor cells by assaying in vivo colony formation inhibition, depends on the drug dosage and length of therapy (after 25-30 days of treatment the colony growth was below 50%). The in vitro inhibition of granulocyte-macrophage colony formation depends on the concentration of drug (10(-7)-10(-5) M is critical for GM colony growth). The results suggest the possibility of the GM-CFC growth testing as an indicator of the progress or side effects of cytotoxic therapy. PMID- 1308059 TI - ABO blood groups system in laryngeal cancer patients and after survival of 3 and 5 years. AB - The analyzed material comprised 200 patients with cancer of the larynx with various locations of the tumour and patients surviving 3 and 5 years after operation. The frequency of ABO blood groups was analysed separately in cases of epiglottis cancer (n = 153) and glottis cancer (n = 37). The frequency of A1, A2, B, A1B, A2B, O blood groups was compared with that in 22,422 healthy individuals living in South Poland. The A2B blood group was significantly more frequent in patients with epiglottis cancer and in those with laryngeal cancer. The difference was not significant after survival of 3 and 5 years. PMID- 1308060 TI - Monoclonal antibodies--why should surgeons be interested? AB - Many different monoclonal antibodies used experimentally and clinically are highly tumor-specific. Radiolabelling of these antibodies has been successfully accomplished. Immunoscintigraphy of primary and metastatic cancers has a reported sensitivity of 59-70%. However, in many studies, operative and histologic confirmation is lacking. Radioimmunoguided surgery is a promising new adjunctive technique for the surgical treatment of colorectal cancer. Its reported sensitivity ranges between 70 and 100% and specificity between 66 and 100%. In approximately one-third of patients with colorectal cancer, additional intraoperative information concerning the presence of subclinical tumors was gained using radioimmunoguided surgery. This system has the potential to assist the surgeon in performing complete resection of cancer and decrease the local recurrence rate. This could be of particular clinical importance for rectosigmoid tumors where the reported local recurrence rate is as high as 30%. Despite the advances made, many problems still need to be resolved. Radioimmunoguided surgery, however, has the potential to change the way surgery for colorectal cancer is being performed. It offers the possibility of improvement in patient survival. PMID- 1308061 TI - The anemia of hyperreactive malarious splenomegaly. PMID- 1308062 TI - The influence of the regional basic diet from northeast Brazil on health and nutritional conditions of mice infected with Schistosoma mansoni. AB - Protein nutritional status indicators were studied in weanling albino Swiss mice infected with S. mansoni and fed the Regional Basic Diet (RBD) from Northeast Brazil, a multideficient diet of low-protein content. Each mouse was infected percutaneously with 80 cercariae. The experiment lasted 63 days. The growth curve, food consumption, protein intake, weight gain, Protein Efficiency Ratio (PER) and Net Protein Ratio (NPR) were the parameters investigated. RBD-fed mice showed a marked weight loss, a lower food and protein intake, a slower body weight gain and lower rates of food protein utilization when compared to casein fed animals. Differences between infected and non-infected mice were not consistent. The present results suggest that the effects of RBD-induced malnutrition on health and nutritional conditions of the mice are more severe than those of Manson's schistosomiasis, in the initial phase of the disease. PMID- 1308063 TI - [Pulmonary compromise in leptospirosis]. AB - To study the pulmonary complications in leptospirosis case records of 23 such patients admitted at the Hospital Universitario Antonio Pedro, Universidade Federal Fluminense, Niteroi, Brasil, were reviewed. Hemoptysis were seen in 21.7% and sputal blood in 30.4% of patients. Arterial gasometry detected hypoxemia and hypocapnia in most cases. Thoracic radiology showed an alveolar pattern in 60% of the patients, alveolo-interstitial in 20%, interstitial in 6%, and in 14% the lungs were considered to be normal. Necropsy of 13 cases showed edema, congestion and hemorrhage in the lungs in all cases. Hyaline membrane was found in 30% and fibrin thrombi in 46% of these cases, resulting in a diagnosis of adult respiratory distress syndrome and acute disseminated intravascular coagulation (consumption coagulopathy) in leptospirosis. PMID- 1308064 TI - [Fonsecaea pedrosoi-caused chromoblastomycosis in the state of Maranhao. I. The clinical, epidemiological and evolutionary aspects]. AB - The aim of this study was to observe the clinical and of epidemiological behavior of chromoblastomycosis in the State of Maranhao. A retrospective and prospective study of 13 cases was performed at the infectious diseases section of the Hospital dos Servidores do Estado do Maranhao, from November, 1988 to July, 1991. In the investigation a protocol record was used with a view to further analysis. A higher prevalence between 50 and 60 years of age (46.1%) and in male patients (92.3%) was noted. Twelve patients (92.3%) were from Maranhao State, and 10 of them (76.9%) came from the western microregion of the State of Maranhao. Regarding occupation, 92.3% were land workers, and most of them presented the lesions on the lower limbs (84.6%) of a vegetant warty aspect, brown in color with itching. Histopathological examination diagnosed chromomycosis in 100% of the cases. Culture was performed in 11 cases, and Fonsecaea pedrosoi isolated in 9 of them. Treatment with 5-fluorocytosine resulted in a good evolutive response. This study indicates the existence of a probable endemic area of chromomycosis in hinterland of Maranhao (western microregion) that hither to unknown. PMID- 1308065 TI - [A quantitative analysis of the mastocytes and eosinophilic granulocytes in the myocardium of Wistar rats chronically infected by Trypanosoma cruzi. A contribution to the knowledge of myocardial fibrosis]. AB - We did mast cell and eosinophil granulocyte counts in the myocardium of forty chronic chagasic Wistar albino rats. We used 10 controls rats and 30 animals with late-stage (8th month) infection of Sao Felipe, Y and Colombian Trypanosoma cruzi strains, with variable degree of chronic myocarditis. We found chronic fibrosing myocarditis (fibrosis) in 40% of the infected animals. It was detected increased mast cell count in the chagasic rats associated with infection and not related with myocardial fibrosis. There was no increase in the eosinophil counts. PMID- 1308066 TI - [The epidemiology of Chagas' disease in a rural area of the city of Teresina, Piaui, Brazil]. AB - In the rural areas of Teresina, 129 triatomines were captured distributed in (a) artificial ecotopes; a house with one Triatoma brasiliensis, one Panstrongylus geniculatus, Rhodnius pictipes, and one Rhodnius prolixus and in a uninhabited chicken house (7 Rhodnius nasutus). (b) Natural ecotopes; Pahus Orbignya martiana (41 Rhodnius neglectus, 33 Rhodnius prolixus and 41 Rhodnius nasutus) and Copernicia cerifera (3 Rhodnius neglectus). The 22.6% of captured triatomines were infected by flagellates similar to Trypanosoma cruzi. Twenty-eight sylvatic mammals were captured and examined. Seven Didelphia albiventris, 2 Rattus rattus and a Tamandua tetradactyla were infected with flagellates. The flagellates found in both triatomines and mammals were morphologically indistinguishable from Trypanosoma cruzi. Serology by the indirect immunofluorescence test for Chagas disease revealed two positive seroreactions of positivity among 123 inhabitants examined. PMID- 1308068 TI - [The experimental infection of Cebus apella sp. monkeys with Trypanosoma cruzi. Its clinical, electrocardiographic and anatomicopathological assessment]. AB - Thirty-two monkeys were captured and adapted to laboratory conditions captives isolated. They were submitted to multiple xenodiagnosis which were negative. Twelve were infected intraperitoneally with different strains of T. cruzi (1.10(5) to 5.10(6)). Twenty were the control group. Between on to six years both the control group and the infected monkeys, were submitted to xenodiagnosis, serological testing clinical examination and electrocardiography. The clinical examination and the electrocardiogram were always normal. The monkey were autopsied and histological examination detected in the infected group four monkeys with evidence of disease: one with parasites in the tissue and three with chronic myocarditis. Parasitaemia was in 66.66% of the monkeys in the acute phase and the serology was positive in 91.66% in the chronic phase. The authors concluded that Cebus monkeys were not susceptible to the development of the disease but they could be utilized to maintain of such strains and studies of serological research in long-terms infections. PMID- 1308067 TI - Molecular biological techniques for the diagnosis of infectious diseases. PMID- 1308069 TI - Crusted scabies in a child with systemic lupus erythematosus. AB - A child with systemic lupus erythematosus who has been treated with prednisone for three years, developed crusted scabies. Scrapings from lesions revealed Sarcoptes scabiei adult mites mad eggs. The patient died with septicemia and renal failure soon after starting topical 20% sulfur. A marked improvement was observed in the cutaneous lesions. PMID- 1308070 TI - [The evaluation of the chance cross reactivity of serological tests for the diagnosis of human immunodeficiency virus and Trypanosoma cruzi infections]. PMID- 1308071 TI - Ten years of occurrence of human Leishmania viannia braziliensis (Lvb) infections in farms around Tres Bracos, Bahia-Brazil. PMID- 1308072 TI - [The transmission of Trypanosoma cruzi via human milk]. PMID- 1308073 TI - Post exposure human-prophylaxis for rabies in developing countries. PMID- 1308075 TI - Alpha-hydroxybutyrate dehydrogenase and the diagnosis of painful crisis in sickle cell anaemia. AB - To assess the value of alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) in the diagnosis of painful crisis (PC) of sickle cell anaemia (SCA), we studied plasma enzyme levels in 55 children with HbSS and 21 control subjects with haemoglobin genotype AA. In 21 children with SCA, mean plasma alpha-HBDH was 373.8 +/- 113.5 micrograms/l during PC and during steady state in 34 children, it was 341.2 +/- 103.4 micrograms/l. These values were significantly higher than that of 128 +/- 19.5 micrograms/l obtained in control subjects. However, the difference between mean plasma alpha-HBDH levels in SCA children in PC and in steady state was 32.6 micrograms/l, t = 1.095; P < 0.2. There was no correlation between alpha-HBDH levels and reticulocyte counts (r = 0.0856; t = 0.4565; 0.7 < P < 0.6). The high levels of alpha-HBDH in patients with SCA is probably due to chronic haemolysis and not marrow infarction. Therefore, alpha-HBDH is of doubtful value in the diagnosis of painful crisis. PMID- 1308076 TI - African histoplasmosis (Duboisii) of the skull with neurological complication--a case report and review of literature. AB - A case of African histoplasmosis of the skull associated with neurological deficit has been reported. There was complete recovery of neurological features after excision of the lesion followed by a course of co-trimoxazole. A review of the available literature indicates the rarity of this particular mode of presentation. The reversibility of the neurological complications makes it important that clinicians increase their awareness of this treatable condition. PMID- 1308074 TI - The specialty choice of clinical year students at the Ibadan Medical School. AB - This is a cross-sectional study of first and final year clinical students of the University of Ibadan, aimed at highlighting the students' preference for specialties, its evolution in the course of training and its correlation with demographic variables. One hundred and twenty-one first year clinical and 150 final year students participated, representing 81% and 89% response rates, respectively. Whereas at the time of study 92.9% of the students intended to specialise, over 81% of this group opted for surgery, internal medicine, paediatrics, obstetrics and gynaecology and general practice. Only 5.5% of the cohort chose radiology, psychiatry, community medicine, anaesthesia and pathology. Surgery was the most popular specialty. No socio-demographic factors seemed associated with specialty choice. Specialty choice, evident before entry into the University in 42.9% of the cohort, evolved during the course of training, being affected mainly by interest aroused during the postings and the need for self-fulfilment. Specialty choice tended to fluctuate over the years. Innovativeness and dedication on the part of teachers can arouse the interest of students during posting, so that specialty choice can be more evenly spread to meet national health manpower needs. PMID- 1308077 TI - The role of neutrophils in acute and chronic inflammation in rats. AB - The effect of neutropenia on acute and chronic inflammatory oedema in rats was assessed using histamine, carrageenan and Freund's complete adjuvant as inducers. Neutropenia (about 85% reduction in peripheral blood neutrophil count) was induced with intraperitoneal administration of 2.5 mg/kg methotrexate for three consecutive days. Acute paw oedemas induced with carrageenan and Freund's complete adjuvant, but not that induced by histamine, were significantly decreased in neutropenic animals compared with controls. In adjuvant-induced chronic knee swelling (Adjuvant arthritis), neutropenia produced small, statistically non-significant, suppressive effect. In contrast, it significantly suppressed adjuvant-induced chronic paw swelling, although suppression was observed only in the late phase component of the swelling. The results suggest that neutrophils are involved in certain acute and chronic inflammatory responses but not in others. PMID- 1308078 TI - Factors influencing academic achievement of medical students in the basic medical sciences. AB - A structured questionnaire was administered to 236 medical and dental students who had just finished the Part I M.B.B.S./B.D.S. degree examination. Apart from personal data of each student, the questionnaire sought information on issues that may affect the student's learning of Anatomy, Biochemistry and Physiology. The scores of all the students in their continuous assessment tests and the finals of the Part I M.B.B.S./B.D.S. examinations in the three subjects were recorded. The results showed that age, repeating the year, performance in continuous assessment tests, having one, seven or eight 'A' grades in the Ordinary Level (O/L) examination significantly affected the overall performance of the students. On the other hand, likeness for a particular subject, mode of entry of the student whether direct or concessional, types of books read, time spent on each subject, having between two and six 'A' grades in O/L, access to hostel accommodation, adequacy or otherwise of financial support and the student's rating of his/her state of health did not significantly influence the performance of the students. The students gained most from lectures while tutorials were rated as being more helpful than practical classes. Multiple choice questions (MCQs) is the preferred mode of assessment. The possible explanation for these findings and their implications for medical education are discussed. PMID- 1308079 TI - Immune complex levels and HBs-antigenaemia in healthy Nigerians and patients with liver diseases. AB - Circulating immune complexes (CIC) were precipitated and assayed in the blood of 19 adult patients with liver diseases and 39 healthy adult Nigerians. The presence of hepatitis-Bs antigen (HBs-Ag) was also investigated in both the sera and CIC of both study groups. CIC levels were not significantly different in the three different liver diseases studied (acute hepatitis, chronic hepatitis and liver cirrhosis). Higher mean CIC levels which were not correlated with the presence of HBs-Ag, were found in the blood of patients, as compared to blood donors. While HBs- Ag was detected in 42.1% of patient's sera, only 12.8% of blood donor sera had detectable antigen. However, 42.1% of CIC from patients had the antigen, while 53.8% of CIC from blood donors also contained the antigen. It is suggested that the high frequency of HBs-Ag in the precipitated CIC of healthy subjects could account for the occurrence of some post-transfusion hepatitis-B infections. PMID- 1308080 TI - "Antimalarial" medicinal plants and their impact on cell populations in various organs of mice. AB - We have investigated the effects of leaf and bark decoctions of Ocimum gratissimum, Azadirachta indica, Morinda lucida and Enantia chlorantha on (a) the course of Plasmodium yoelii nigeriensis malaria (b) reticulocyte and haematocrit values and (c) nucleated cell numbers in the spleen, bone marrow, peritoneum, liver and peripheral blood of Swiss albino mice. Results obtained showed that normal mice infected with the parasite (10(4)/mouse) suffered fulminant parasitaemia which resulted in death, 7-10 days later. All infected mice treated with chloroquine survived. On the other hand all infected mice treated with the medicinal plants exhibited varying percentages of chemosuppression of early parasitaemia which did not lead to their survival. The total number of nucleated cells in the liver, spleen and peripheral blood of malaria-infected mice increased enormously before the animals died. Such increases were maintained in other groups of mice treated with the medicinal plants. In the non-infected mice, O.gratissimum and E. chlorantha administration increased the number of nucleated cells in the spleen, liver and peripheral blood. Chloroquine on the other hand decreased the number of nucleated cells in both the malaria-infected and un infected mice. There was also a decrease in reticulocyte numbers in the blood of normal mice injected with chloroquine. Conversely reticulocyte numbers increased in normal mice administered with some medicinal plants. Acute and chronic toxicity tests revealed that some of the medicinal plants were much more toxic than others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308081 TI - Screening for Listeria monocytogenes and other related species from faecal specimens at the Lagos University Teaching Hospital, Lagos. AB - Four hundred and twenty faecal specimens from patients with acute gastroenteritis and apparently healthy persons who reported at the Lagos University Teaching Hospital (LUTH) between October, 1988 and May, 1989 were investigated for faecal carriage of Listeria monocytogenes and other related species. Of these specimens, none was positive for Listeria species. However, the mannitol--fermenting Listeria species now Murraya grayi sub species grayi and Murraya grayi sub spp. murrayi representing 0.95% (4 out of 420) were isolated. Other well known enteric pathogens isolated in the course of this study were Escherichia coli (11.4%), Salmonella typhi (7.1%) and Yersinia species (1.4%). PMID- 1308082 TI - Puerperal haematological indices in the Nigerian. AB - Haematological indices were studied longitudinally in 84 healthy pregnant women at term and on days 1, 3, 5, 7 and 42 in the puerperium. Haemoglobin and haematocrit increased on day 1 after delivery, reduced on days 3 and 5 then started rising such that by day 42, the normal haemoglobin in African non pregnant women was achieved. Leucocyte and neutrophil count increased significantly on day 1 but started falling thereafter and by day 5 the value had returned to normal. The lymphocyte, eosinophil and monocyte count did not show significant variation within the period of study. The platelet count in the primipara showed significant change on days 3 and 5. The variations in haemoglobin, haematocrit, leucocyte and platelet count in the puerperium were more marked in the primipara than the multipara and grandmultipara. PMID- 1308083 TI - Ultrasound monitoring of ovarian follicular growth during spontaneous cycles in Nigerian women. AB - Thirty-nine spontaneous cycles in 34 women (22 patients from the infertility clinic and 12 normal volunteers) were serially studied by ultrasound to monitor follicular growth for ovulation prediction and detection. Ovulation was also confirmed by a mid-luteal phase progesterone assay using WHO match RIA kits. Ovulation occurred from the left ovary in 21 cycles (54%) and from the right ovary in 18 cycles (46%). The maximum follicular diameter prior to ovulation was 21.0 +/- 3.48mm with a range of 15-28 mm. The maximum pre-ovulatory size in the group of infertile patients 21.4mm (range 15-28 mm) was not statistically different from the size in normal volunteers 20.8mm (range 15.5-27mm) (P > 0.05). Bilateral ovulation occurred in two patients. Changes in shape and/or size of the follicle mostly associated with increased internal echoes were the indices of ovulation in 84.7% of cases. Follicular diameter of 15mm may indicate imminent ovulation in Nigerian women. Infertility management procedures such as artificial insemination, timed sexual intercourse may commence just before or once this follicular size has been attained until ovulation is detected. PMID- 1308084 TI - Malignant childhood tumours in Calabar, Nigeria. AB - Children suspected with cancers seen during a 5-year period (Jan 1983-Dec 1987) in the University of Calabar Teaching Hospital (UCTH) Calabar, Nigeria were prospectively studied. A total of 60 cases were confirmed in those aged below 15 years with a majority (38.3%) of the children under 3 years. The pattern shows a preponderance of Burkitt's lymphoma followed by nephroblastoma and soft tissue sarcoma as the commonest malignancies. A low relative frequency of leukaemias (8.3%) and no intracranial tumours were encountered. This pattern closely resembles that of other Nigerian reports but contrasts with the situation in Britain and America, with their high leukaemia and intracranial tumour frequency ratios. Generally, there appears to be a low prevalence of malignancies among children in Calabar and presumably the south-eastern part of Nigeria. Difficulties in their management are attributable to late presentation, high patient default rate, complete lack of radiotherapy, and shortage of chemotherapeutic agents. PMID- 1308085 TI - Alzheimer's disease in Nigeria. AB - The age-related dementias of the elderly (those aged 65 years or more) are of major public health importance in developed countries. Developing countries, most of which are undergoing epidemiological transition and greying of population, currently contain more than half of the world's population of elderly, a proportion that would reach 75% by 2020. Apart from reports from China, there is little or no information on the dementias of the elderly in developing countries. Alzheimer's disease, which accounts for two-thirds of dementia of the elderly in Caucasian population, is under-documented and believed to be rare in black Africans. But black Americans who are of black African lineage commonly suffer from Alzheimer's disease. A recent autopsy survey of the brains of elderly Nigerians showed absence of senile plaques and neurofibrillary tangles, the pathognomonic histologic lesions of Alzheimer's disease and ageing found in 25% to 80% of normal undemented elderly Caucasians and Japanese. In a community-based door-to-door survey of a population of 9000, including 932 elderly Nigerians, no subject with dementia as defined by DSM-IIIR was found, although there was significant decline of cognition with age, female sex and less than 6 years of formal education. The distribution of cognitive scores is a highly skewed unimodal curve. We emphasize the potential value of cross-cultural epidemiological studies of ethnic groups in different environments and with different prevalence ratios of Alzheimer's disease, in identifying putative environmental factors for this disease. PMID- 1308086 TI - Screening for obstruction of the vas deferens in Nigerian men with azoospermia using the alpha-glucosidase reaction in semen. AB - Obstruction of the vas deferens has been screened for, using the alpha glucosidase reaction in seminal plasma as previously described by Comhaire. Eighteen patients with azoospermia were studied. The result showed positive reaction in 17 patients (95.0%) and only a weak yellow reaction in 1 patient. The results did not corroborate the working hypothesis that the azoospermia was due to obstruction of the vas deferens. The implications of this findings in the management of male infertility in Nigeria are discussed. PMID- 1308087 TI - Influence of four Nigerian food additives on the mutagenicity of aflatoxin B1. AB - The mutagenicity of aqueous extracts of four Nigerian food additives namely Xylopia aethiopica (Xa), Monodora species (Ms); fermented Litrillus lanatus-ogiri (Og) and fermented Parikia africans (African locust bean)-Iru (Ir) alone and in combination with different concentrations of aflatoxin B1 (0.05 microgram-0.25 micrograms) in the presence and absence of fecalase was studied using the Ames' salmonella mutagenicity assay system. Preliminary screening tests show the tester strain TA98 to be the most sensitive of the four tester strains (TA97, TA98, TA100, TA102) screened. The most mutagenic of the doses of the extracts are 3mg each of Xa and Ms per plate and 5mg each of Og and Ir per plate. A combination of these doses with different concentrations of aflatoxin B1 resulted in an enhanced mutagenicity of aflatoxin B1. The increases could not be accounted for by additive mutagenicity of the extracts and aflatoxin B1. Fecalase further increased the effects resulting from these combinations with the exception of Xa which showed a decrease in mutagenic induction. The increase may be indicative of the presence of some mutagenic glycosides in the extracts. PMID- 1308088 TI - Beliefs and attitudes of clinical year students concerning medical specialties: an Ibadan medical school study. AB - In order to understand their attitudes to 10 medical specialties, a 40-item self report questionnaire was administered to the first and final year clinical students of the University of Ibadan. One hundred and twenty-one first year and 150 final year students participated, constituting 81% response rates respectively, in the two classes. The findings indicate that many factors influence specialty choice, the principal ones being: expectation of material rewards; societal appreciation of specialty and specialists; response of specialty patients to treatment; and the role of specialty teachers. It seems that specialties viewed positively in these dimentions (such as surgery, paediatrics, internal medicine, and obstetrics and gynaecology) are more highly favoured than the others (such as radiology, pathology, psychiatry, anaesthesia and community medicine), which were viewed rather negatively in this regard. Generally speaking, opinion on specialties was similar, not only between the two classes, but also between this cohort and comparable groups in developed nations. In order to enhance the spread of specialty manpower development to meet the goal of health care for all, suggestions are made about how to improve the positive appreciation of the less favoured specialties among undergraduates. PMID- 1308089 TI - Lasers in surgery. AB - In January 1991 the winter meeting of the Surgical Research Society was held at St. Bartholomew's Hospital and the Institute of Education, London. During the meeting a symposium was held entitled 'Shedding light on lasers'. Speakers addressed the general principles of lasers, laser-tissue interactions and the applications of lasers in gastro-enterology and in vascular disease. This was followed by an open discussion of the current indications, complications and outcome, together with future possible applications for lasers in medicine. PMID- 1308090 TI - Risk factors for female and male infertility: results of a case-control study. AB - In order to evaluate male and female risk factors for infertility in a case control study, we have compared all couples in a French administrative region consulting for primary or secondary infertility (of more than one year's duration) with couples in which the woman had given birth during the year of the study. For any one couple, a history of varicocele, male genital infections or testis damage multiplies the risk of primary infertility by a factor of 28, 3 and 4 respectively, and previous female infections (salpingitis) multiply the risk by 45. Similarly, a history of ectopic pregnancy, sexually transmitted diseases or salpingitis multiplies the risk of secondary infertility by a factor of 5, 4 and 7 respectively, and a history of varicocele multiplies this risk by 4. PMID- 1308091 TI - Sedation for children undergoing magnetic resonance imaging and computed tomography. PMID- 1308092 TI - Post-traumatic stress disorder. AB - The management of post-traumatic stress disorder depends on the nature of the stress, the personality of the victim, and the clinical orientation of the therapist. Traumatic situations may be experienced by individuals or by groups, and may be isolated incidents (such as unexpected civil disasters) or continuing occupational hazards, such as are experienced by soldiers, firemen or police. The first concern of therapists, whatever their methods of treatment, is an understanding of the nature of the trauma, and of the inherent differences in each type. This paper seeks to identify such differences. Some general therapeutic principles are then suggested. PMID- 1308093 TI - Suicide in the home in relation to gun ownership. AB - BACKGROUND: It has been suggested that limiting access to firearms could prevent many suicides, but this belief is controversial. To assess the strength of the association between the availability of firearms and suicide, we studied all suicides that took place in the homes of victims in Shelby County, Tennessee, and King County, Washington, over a 32-month period. METHODS: For each suicide victim (case subject), we obtained data from police or the medical examiner and interviewed a proxy. Their answers were compared with those of control subjects from the same neighborhood, matched with the victim according to sex, race, and age range. Crude and adjusted odds ratios were calculated with matched-pairs methods. RESULTS: During the study period, 803 suicides occurred in the two counties, 565 of which (70 percent) took place in the home of the victim. Fifty eight percent (326) of these suicides were committed with a firearm. After excluding 11 case subjects for various reasons, we were able to interview 80 percent (442) of the proxies for the case subjects. Matching controls were identified for 99 percent of these subjects, producing 438 matched pairs. Univariate analyses revealed that the case subjects were more likely than the controls to have lived alone, taken prescribed psychotropic medication, been arrested, abused drugs or alcohol, or not graduated from high school. After we controlled for these characteristics through conditional logistic regression, the presence of one or more guns in the home was found to be associated with an increased risk of suicide (adjusted odds ratio, 4.8; 95 percent confidence interval, 2.7 to 8.5). CONCLUSIONS: Ready availability of firearms is associated with an increased risk of suicide in the home. Owners of firearms should weigh their reasons for keeping a gun in the home against the possibility that it might someday be used in a suicide. PMID- 1308094 TI - Suicide--what can be done? PMID- 1308095 TI - Objective clinical evaluation of physical impairment in chronic low back pain. AB - The aim of this study was to investigate physical impairment in patients with chronic low back pain, to develop a method of clinical evaluation suitable for routine use, and to consider the relationship between pain, disability, and physical impairment. Twenty-seven physical tests were investigated. Permanent anatomic and structural impairments of spinal deformities, spinal fractures, surgical scarring, and neurologic deficits were excluded as not relevant to the patient with low back pain in the absence of nerve root involvement or previous surgery. Three consecutive 20-patient reproducibility studies were used to develop reliable methods of examination for 23 of the tests. Only four tests were excluded as unreliable: sacral angle, pelvic tilt, and separate lumbar and pelvic extension, none of which are part of routine clinical examination or have any proven relationship to disability. The remaining 23 physical tests were evaluated in 70 asymptomatic subjects and 120 patients with chronic low back pain. Passive knee flexion, passive hip flexion, hip flexion strength, hip abduction strength, pain reproduction on each of these tests, and the prone extension strength test were excluded because they were too closely related to nonorganic and behavioral responses to examination. Eight tests successfully discriminated patients with low back pain from normal subjects and were significantly related to self-report disability in activities of daily living: pelvic flexion, total flexion, total extension, lateral flexion, straight leg raising, spinal tenderness, bilateral active straight leg raising, and sit-up. Factor analysis failed to demonstrate an underlying statistical dimension of physical impairment. However, an empirical combination of total flexion, total extension, average lateral flexion, average straight leg raising, spinal tenderness, bilateral active straight leg raising, and sit-up provided an equally satisfactory alternative. Simple cut-offs from normal subjects made the scale simple and quick to use. This final scale successfully discriminated 78% of patients and normal subjects and explained 25% of the variance of disability, with a specificity of 86% and sensitivity of 76%. This scale provides an objective clinical evaluation that meets the criteria for evaluating physical impairment, yet is simple, reliable, and suitable for routine clinical use. It should, however, be emphasized that all the tests included in the final scale are measures of current functional limitation rather than of permanent anatomic or structural impairment. This raises questions about the physical basis of permanent disability due to chronic low back pain. PMID- 1308096 TI - Simultaneous trapezium and Bennett's fractures. PMID- 1308097 TI - Renal failure after flunixin meglumine administration. PMID- 1308098 TI - Red cell aplasia caused by human parvovirus B19 in acute leukaemia. PMID- 1308099 TI - Placement of semipermanent vascular access devices (Hickman or Groschong catheter) PMID- 1308100 TI - [Comments on the contribution, Therapy of hyperammonemia in carbamylphosphate synthetase deficiency with peritoneal dialysis and venovenous hemofiltration, by B. Lettgen et al]. PMID- 1308101 TI - Sural nerve conduction parameters in normal subjects related to age, gender, temperature, and height: a reappraisal. AB - Failure to take body height into considerations in the evaluation of nerve conduction velocities (CV) has recently been deemed unacceptable. This statement prompted the present study. Besides height, the influence of age, gender, and temperature was studied in 92 normal subjects, half of whom were females. The CV decreased 0.9 m/s per 10 years increase in age, the same in women and men aged 15 to 44 years. Mean temperature between distal and proximal ends of the nerve segment examined increased 6.1 +/- 0.3 degree C after heating followed by a CV increase of 7.0 +/- 0.5 m/s. The CV decreased 0.15 m/s per 100-mm increase in heights. When considering 37 individuals aged 25 to 34 years only, the CV increased 0.34 m/s per 1-m increase in height. In both instances, the changes were within the experimental error (2.3%) of the method. PMID- 1308103 TI - Assisted conception on the NHS. PMID- 1308102 TI - Sleep related upper airway obstruction and hypoxaemia in sickle cell disease. AB - A cohort of 53 patients (age range 1.9-16.5 years) with sickle cell disease (49 homozygous SS and four S beta zero-thalassaemia) was studied for evidence of sleep related upper airway obstruction (UAO). This involved (i) a clinical assessment based on a history of snoring, a score of tonsillar size, and (for 50 patients) overnight multichannel respiratory recordings, and (ii) a blinded analysis of arterial oxygen saturation (SaO2) from the above recordings, and comparison with results from 50 healthy age matched controls of both white (n = 25) and Afro-Caribbean race. There was no difference in the baseline SaO2 values of the white and Afro-Caribbean controls. Eighteen patients with sickle cell disease (36%) were found to have sleep related UAO. The blinded analysis showed that eight patients (16%) had episodic hypoxaemia (SaO2 less than or equal to 80%, a value not observed in controls) and/or low baseline SaO2 values (less than 95.8%, the lowest value seen in the controls). Postoperative assessment was undertaken in 15 patients who underwent adenotonsillectomy. All demonstrated an improvement in symptoms and a reduction or abolition of episodic hypoxaemia. Of the 47 patients assessed when free of UAO (not demonstrated on screening, n = 32, or resolved following surgery, n = 15), seven continued to show baseline hypoxaemia. Sleep related UAO and baseline hypoxaemia are common complications of sickle cell disease in children. PMID- 1308104 TI - Serum lipoprotein(a) levels in racially different populations. AB - Lipoprotein(a) is an atherogenic lipoprotein which has been studied predominantly in white populations. Serum lipoprotein(a), serum lipids, and apolipoproteins A-I and B were quantified in 1991 in a total of 300 sex-matched samples derived from five different ethnic groups. Three population samples of Asian origin (Tibet, Korea, and China), one population sample of West African origin (Nigeria), and one Western population sample (Belgium) were included. All serum samples had been collected in the past (3-11 years previously) and had been stored at -80 degrees C since then. Thirty serum samples from males and 30 serum samples from females were analyzed from each ethnic group. Overall median lipoprotein(a) levels in Koreans, Chinese, Tibetans, Nigerians, and Belgians were 99, 89, 49, 134, and 80 mg/liter, respectively. Lipoprotein(a) frequency distributions were highly skewed to the right in all populations, with the Nigerian distribution showing less skewness than the Asian and Western plots. All distributions became nearly gaussian after logarithmic transformation. No statistical difference was found between the mean log lipoprotein(a) values of the sexes (4.43 +/- 1.01 mg/liter (standard deviation) in men; 4.44 +/- 1.08 mg/liter in women). Pearson correlation analysis of both sexes combined revealed no statistically significant correlation (at the p less than 0.01 level) of log lipoprotein(a) with age, height, weight, body mass index, cholesterol, high density lipoprotein cholesterol, apolipoprotein A-I, or apolipoprotein B within any of the population groups studied or after pooling of all population groups. PMID- 1308105 TI - [Research in the practice area. Wishing it, wanting it, daring it--but why do it?]. PMID- 1308106 TI - [Burn injuries. When patients "smell bad"]. PMID- 1308107 TI - [Comments on revision of framework plans]. PMID- 1308108 TI - Histological sampling of the endometrium--a comparison between formal curettage and the Pipelle sampler. PMID- 1308109 TI - Introduction to background papers for the suggested changes to DSM-IV: cognitive disorders. PMID- 1308110 TI - Assisted conception on NHS. PMID- 1308111 TI - Sex ratios of affected and transmitting members of multiple case families with neural tube defects. AB - In order to study the genetic aspects of the relation between neural tube defects and sex, we selected families with at least two closely related affected members. The sex ratios of both affected and normal transmitting persons were determined in these multiple case families. Our results indicate that there is a relation between the position of the lesion in the spine and sex. Furthermore, the affected persons in one family show significant concordance for sex as shown by the analysis of families with just two affected members. To our surprise, the group of normal transmitters appears to consist of significantly more females than males. This is in contrast to similar families with non-syndromic cleft lip +/- palate, where males predominate both among affected persons and normal transmitters. Finally, affected females most often inherited the predisposition to a neural tube defect from their mother. The possible role of inherited factors is discussed. PMID- 1308112 TI - Subaortic obstruction in hearts with a univentricular connection to a dominant left ventricle and an anterior subaortic outlet chamber. Results of a staged approach. AB - In 1984 we reported a 56% mortality after major cardiac operations for patients with univentricular connection to a dominant left ventricle, an anterior subaortic outlet chamber, and subaortic obstruction. Since then we have adopted a staged approach to this repair. Between 1984 and 1989 32 patients had such operations. The overall mortality has decreased (16%; p < 0.001). The current cohort was divided by subaortic gradient into three subgroups for comparison with the cohort reported in 1984. Staging improved the outcome in patients with gradients greater than 40 mm Hg (mortality of 17% compared with 67% from 1984; p = 0.05). Patients with gradients from 10 to 25 mm Hg who had a single-stage operation had the best outcome (mortality 6%). Survival has improved. Many factors, including increased awareness of the detrimental effects of subaortic obstruction, improved surgical techniques, better perioperative care, and the appropriate application of a staged repair, have contributed to this improvement. We recommend simultaneous relief of obstruction and a modified Fontan operation for patients with subaortic gradients less than 25 mm Hg. Those with gradients greater than 40 mm Hg should have repair in two stages. It is unclear whether a one-stage or two-stage approach is better for patients with gradients between these extremes. PMID- 1308113 TI - Dental handpieces and sterilization standards. PMID- 1308114 TI - Recombinant versus plasma-derived hepatitis B vaccine: comparison of immunogenicity in medical students. AB - A group of 92 medical students were immunized with a commercial recombinant hepatitis B vaccine (Engerix B). Antibody responses were determined and compared with those to plasma-derived Pasteur vaccine, obtained in 1986. Antibody concentrations were significantly higher in the group given recombinant vaccine, therefore this vaccine has superior immunogenicity and probably confers extended duration of protection. PMID- 1308115 TI - Laryngospasm during transtracheal high frequency jet ventilation. AB - A 74-year-old woman developed severe cardiovascular depression during percutaneous transtracheal high frequency jet ventilation for laser surgery of the epiglottis. This was found to be caused by acute airway obstruction secondary to severe laryngospasm. We recommend profound neuromuscular blockade during percutaneous transtracheal jet ventilation, in order to prevent this complication. PMID- 1308116 TI - A fasted patient? PMID- 1308117 TI - Pseudohyperphosphataemia in multiple myeloma. PMID- 1308118 TI - Surfactant replacement therapy--time for thought. PMID- 1308119 TI - Post-traumatic stress disorder in combat veterans. PMID- 1308120 TI - Suicide in the home in relation to gun ownership. PMID- 1308121 TI - Suicide in the home in relation to gun ownership. PMID- 1308122 TI - Current cup designs for obstetric vacuum extraction. PMID- 1308123 TI - Everyone should be tested for iron disorders. AB - Routinely measuring iron status is necessary because about 6% of Americans have negative iron balance, about 10% have a gene for positive balance, and about 1% have iron overload. Deviations from normal iron status are as follows. (a) Stage I and II negative iron balance, ie, iron depletion: In these stages iron stores are low and there is no dysfunction. In stage I negative iron balance, reduced iron absorption produces moderately depleted iron stores. Stage II negative iron balance is characterized by severely depleted iron stores. More than half of all cases of negative iron balance fall into these two stages. When persons in these stages are treated with iron, they never develop dysfunction or disease. (b) Stage III and IV negative iron balance, ie, iron deficiency: Iron deficiency is characterized by inadequate body iron for normal function, producing dysfunction and disease. In stage III negative iron balance, dysfunction is not accompanied by anemia; anemia develops in stage IV negative iron balance. (c) Stage I and II positive iron balance: Stage I positive balance usually lasts for several years with no dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction or disease. Iron removal prevents progression to disease. Iron overload disease develops in stage II positive iron balance after years of iron overload has caused progressive damage to tissues and organs. Again, iron removal stops disease progression. There are a variety of indicators of iron status. Serum ferritin is in equilibrium with body iron stores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308124 TI - Invited letter concerning: systemic outflow tract obstruction in the patient with a single functional ventricle. PMID- 1308125 TI - Siamese calves. PMID- 1308126 TI - The effects of isotretinoin on the axial skeleton and the retinoid effect. PMID- 1308127 TI - Blood and breath alcohol concentrations. PMID- 1308129 TI - Awake blind nasal intubation. PMID- 1308128 TI - Obstetrics in family practice. PMID- 1308130 TI - Glycemic control and complications in type II diabetes. Design of a feasibility trial. VA CS Group (CSDM) AB - OBJECTIVE: To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection. RESEARCH DESIGN AND METHODS: This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40-69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 x 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria. CONCLUSIONS: This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points. PMID- 1308131 TI - Diagnosis of systemic histoplasmosis in patients with AIDS. AB - To compare various laboratory methods for diagnosis of systemic histoplasmosis, we retrospectively reviewed the charts of 165 patients with AIDS (acquired immunodeficiency syndrome). In eight of those patients, systemic histoplasmosis was confirmed by laboratory techniques. The laboratory methods used were histomorphology and microbiology. Tissues and fluids used for fungal cultures and histochemical stains included blood, bone marrow, lung, skin, pleura, esophagus and colon biopsy specimens, sputum, cerebrospinal fluid, bronchial washing/brushing, and pleural and peritoneal fluids. Results were positive in 83% of blood cultures and 71% of bone marrow cultures, making these tissues the best sources of Histoplasma organisms for microbiologic study. Similarly, Histoplasma sp could be demonstrated by fungal stains in 75% of bone marrow biopsy specimens as the main source for morphologic documentation of systemic histoplasmosis. The other tissues and fluids were only occasionally positive either microbiologically or morphologically. There was cross-positivity between morphologic and microbiologic methods in 80% of confirmed cases, making both methods equally reliable. However, the results were obtained within 48 hours by histomorphology, allowing prompt initiation of antifungal therapy. Although more specific results were produced by microbiologic methods, it took 18 to 35 days to grow the organism. PMID- 1308132 TI - Mitral valve prolapse and keratoconus. PMID- 1308133 TI - The discovery rule and statute of limitations: are you as safe as you think? PMID- 1308135 TI - Professional growth, professional ethic. The development of a personal philosophy. PMID- 1308136 TI - Operatory capitalism: how to profit from your hygienist. PMID- 1308134 TI - The new Texas income tax--a whimper, not a bang. PMID- 1308137 TI - Roentgen ray anomalies. PMID- 1308138 TI - The Benton E. Crawford radiograph of the month. Unicystic ameloblastoma. PMID- 1308139 TI - The periodontal pocket--what does it mean? PMID- 1308140 TI - Management 101. PMID- 1308141 TI - Differential diagnosis in dentistry. PMID- 1308142 TI - Roentgen ray anomalies. Mucous retention cyst of maxillary sinus. PMID- 1308143 TI - Initial interview and the therapeutic alliance. PMID- 1308144 TI - General Dental Council. Professional Conduct and Fitness to Practice. PMID- 1308145 TI - Dental radiography and the dental surgery assistant. PMID- 1308146 TI - Stress and the dental surgery assistant. PMID- 1308147 TI - An avenue of hope. PMID- 1308148 TI - Local anesthesia privileges for hygienists? PMID- 1308149 TI - A new approach to evaluation of orthodontic record casts. PMID- 1308150 TI - A review of second molar extractions in orthodontics. PMID- 1308151 TI - Case report--midline shift, overbite and overjet. PMID- 1308152 TI - Rick-A-Nator Part 2. PMID- 1308153 TI - Peripheral and central regulation of IL-6 gene expression in endotoxin-treated rats. AB - The distribution of IL-6 mRNA in the rat brain was studied by in situ hybridization using 35S-labelled oligonucleotides. The mRNA encoding IL-6 was found in hippocampus, hypothalamus, cerebellum as well as in other brain areas. Microscopic analyses revealed both neuronal and glial cell localization of the mRNA. Subsequently, Northern blot analyses were performed with RNA isolated from spleen, adrenals, pituitary gland, hypothalamus, hippocampus and cerebellum of rats injected intraperitoneally with a non toxic dose of LPS. A rapid induction of the IL-6 mRNA was observed in the peripheral organs, whereas no change in IL-6 transcripts could be measured in the brain. It is concluded that the local synthesis and release of IL-6 in pituitary and adrenal gland might be involved in the activation of the HPA axis following an endotoxin challenge. PMID- 1308154 TI - Is the 5 alpha-reductase-3 alpha-hydroxysteroid dehydrogenase complex associated with the myelin in the peripheral nervous system of young and old male rats? AB - The formation of the 5 alpha-reduced metabolites of testosterone, 5 alpha androstan-17 beta-ol-3-one (dihydroxytestosterone, DHT) and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol) was evaluated in sciatic nerve fragments and homogenates and in the myelin purified from the sciatic nerve of adult (60-90-day old) male rats. The effects of aging on the metabolism of testosterone in the sciatic nerve was also evaluated using 20-month-old animals. In the sciatic nerve, tissue homogenization and myelin purification are associated with a marked decrease in the 5 alpha-reductase activity; these data do not appear to be consistent with a possible association of the enzyme with myelin membranes, as it occurs in the CNS. However, the results may be subject to other interpretations which are presented in the discussion. The formation of 3 alpha-diol is higher in sciatic nerve fragments than in homogenates or in the purified myelin. This occurs when testosterone is used as the substrate. In aged animals, the same pattern is observed but at a lower level. In the incubations in which the formation of 3 alpha-diol was evaluated using DHT as the substrate in fragments, homogenates and purified myelin of the sciatic nerve of either adult or old animals, it was found that the yields of this metabolite are higher than those obtained following incubation with testosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308156 TI - Role of serotonin in heat adaptation: an experimental study in the conscious young rat. AB - The possibility that serotonin may play a role in heat adaptation was examined in a rat model of heat stress (HS). Subjection of animals to acute 4 h HS (but not to 1 h and 2 h duration) in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25 cm/s) resulted in profound hyperthermia (41.68 +/- 0.25 degrees C) associated with behavioural salivation and prostration. This experimental condition simulates the out door environmental conditions of Varanasi, India during the month of June. Measurement of serotonin (5-hydroxytryptamine, 5-HT) content in the plasma and brain showed a profound increase of the amine by 462% and 187% respectively from the control group. Morphological examination in these animals revealed marked cell changes in the brain at both light and electron microscopic level. Thus chromatolysis, shrunken and dark neurons along with a general sponginess of the gray and white matter was quite frequent in all the brain regions. At ultrastructural level, perivascular edema, damage to pre- and postsynaptic terminals, swollen neurons and glial cells, splitting of myelin and vacuolation was very common throughout the whole brain. The microvessels were mainly collapsed and a diffuse infiltration of lanthanum ion within the endothelium was common. Occasionally, lanthanum could also be seen within the basement membrane. However, the tight junctions were mainly intact. On the other hand, when animals exposed to chronic heat stress of 1 h duration at the same intensity for 7 days and then subjected to a 4 h HS on the 8th day, resulted in only minor symptoms. Thus these 4 h heat stressed animals did not exhibit hyperthermia or increased serotonin levels in plasma and brain as compared to the animals exposed to chronic HS of 1 h duration until alone 7th day. These heat adapted animals did not show any marked cell changes in the brain. However, the values of circulating 5-HT level and rectal temperature of these chronically heat stressed animals (for 1 h daily) were mild but significantly elevated on the 7th day as compared to the intact control animals. These results show that: 1. chronic HS of short duration induces heat tolerance; 2. the circulating 5-HT level some how appears to play an important role in the pathophysiology of HS; hand in the physiological mechanism(s) of secondary heat adaptation. PMID- 1308155 TI - Effect of protease inhibitors and substrates on 3,5,3'-triiodothyronine binding to rat liver nuclear receptors. AB - The effect of protease inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-carbobenzoxy-L-phenylalanine chloromethyl ketone (ZPCK) at concentrations ranging from 1.5 x 10(-6) mol/l to 1.5 x 10(-4) mol/l on the specific binding of 3,5,3'-triiodothyronine (T3) to rat liver nuclear receptors was evaluated. Both TPCK at 1.5 x 10(-5) mol/l (P < 0.001) and ZPCK at 1.5 x 10( 6) mol/l (P < 0.05) showed the inhibition of T3 binding to nuclear receptors. The evaluation of T3 binding data following separation of unbound TPCK from treated nuclear receptors on a Sephadex G-25 column showed that the inhibition of T3 binding was irreversible, since a substantial decrease of the equilibrium association constant (Ka) was found when compared to the mock samples lacking TPCK. In addition, similar inhibitory effect on T3 specific binding to rat liver nuclear receptors was found at 5.0 x 10(-4) mol/l by protease substrates L tyrosine benzyl ester (P < 0.001), L-tyrosine ethyl ester (P < 0.02), L tryptophan methyl ester (P < 0.02) and L-tryptophan ethyl ester (P < 0.05). The data suggest that: 1. both protease inhibitors and substrates tested inhibited T3 specific binding to T3 nuclear receptors; 2. this may support the hypothesis that T3 receptors like other receptors encoded by c-erbA gene possess a site that recognize both serine protease inhibitors and substrates in its hormone binding domain. PMID- 1308157 TI - Neonatal erythropoiesis. II. Bone marrow and splenic erythropoietic activity: data suggest erythropoietin transfer via maternal milk. AB - In this study we examined erythropoiesis in the bone marrow and spleen of 9 to 12 day-old neonatal rats suckled by bleeding-induced anemic mothers. Quantitative evaluations of the spleen revealed a significant decrease in total numbers of nucleated RBC/mg spleen in 11-day-old pups nursed by the anemic mother which returned to control values by day 12. A significant reduction in total numbers of nucleated RBC/mg marrow was seen in both 11 and 12-day-old pups of anemic mothers when compared to control values. These results suggest that: 1. Ep is transmitted to suckling rats via the maternal milk; 2. Ep in the neonate exerts its influence predominantly at the level of the differentiated erythroid compartment probably by causing a shortening of the mean transit time of the proliferating erythroblast compartment and/or by decrease in the maturation time of the nonproliferating orthochromatic and reticulocyte compartments; 3. the regulation of erythropoiesis in the neonate differs from that in the adult. PMID- 1308158 TI - Immunoreactive glucagon and insulin in mammary secretion and blood in women during the periparturient period. AB - The concentrations of glucagon (G) and insulin (I) in the isolated when fraction of colostrum and plasma were determined by radioimmunoassay in 30 women on the last day of pregnancy, on the parturition day and during 7 consecutive postpartum days. The levels of G and I in colostrum were high on the last day of pregnancy (15.41 +/- 0.75 ng/ml and 256.9 +/- 32.7 microU/ml, resp.) and on the day of parturition (13.41 +/- 0.63 ng/ml and 279.5 +/- 41.9 microU/ml, resp.), while relatively lower values were observed on the next day (10.1 +/- 0.41 ng/ml and 194.7 +/- 19.3 microU/ml, resp.). During the next 4 days after parturition the concentrations of these hormones gradually decreased almost to the same basal level as observed in plasma. High hormone concentrations in mammary secretion during the periparturition period were probably caused by intensified transfer through blood-mammary gland barrier, and could reflect increasing needs for these hormones by developing mammocytes and by the newborns adapting to the extrauterine life. In conclusion, a high amount of G and I in mammary secretion may have physiological importance for the neonate. No statistically significant correlation in the hormone concentration between colostrum and plasma were noted. PMID- 1308159 TI - The sinus lift procedure: an alternative to the maxillary subperiosteal implant. AB - Technical advances now allow implants to be placed when pneumatization of the sinus has left insufficient bone to engage an endosseus implant. Augmenting material, such as a mixture of resorbable hydroxylapatite and demineralized freeze-dried bone, is grafted into the sinus cavity. This creates a new alveolar ridge to support endosseous implants. PMID- 1308160 TI - Implant fixture position registration at the time of fixture placement surgery. AB - The implant registration procedures usually take place at the fixture uncovery surgery, months after the implant placement. In this article, the authors describe a technique for single implant fixture registration during the surgical placement of that fixture. The rationale and advantages of this procedure are also discussed. PMID- 1308161 TI - Our profession of dentistry should heed fair warning. PMID- 1308162 TI - Treatment of implants demonstrating periapical radiolucencies. AB - This article presents two implant cases where a periapical radiolucency developed, with a sinus tract, while the implants were still submerged. A corrective surgical treatment for these unique lesions is detailed, and the possible etiologies are discussed. PMID- 1308163 TI - Replacing a failed resin-bonded fixed partial denture with a single tooth implant. AB - When adequate width and height of remaining alveolar bone is present, the implant supported fixed prosthesis is an excellent alternative in replacing a missing tooth. The prosthetic tooth, supported by an endosseous implant, emerges from the tissue in a manner which resembles the natural tooth it replaces better than any other treatment option available. This article presents one clinical case history, preclinical treatment phase, and actual clinical treatment. PMID- 1308164 TI - The use of free gingival grafts to improve the implant soft tissue interface: rationale and technique. AB - Utilization of implants of all types to restore partially or fully edentulous patients to occlusal form and function continues to increase. The ability of the implant/bone/soft tissue interface of the implant-retained prosthesis to ward off a constant influx of microorganisms and their byproducts becomes a critical factor in the health and longevity of dental implants. The purpose of this article is to describe the rationale and technique for providing an improved quality of tissue adjacent to implant abutments. PMID- 1308165 TI - The cytogenetics of haematological malignancies. PMID- 1308166 TI - Down syndrome and chromosome 21 abnormalities in leukaemia. PMID- 1308167 TI - Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. AB - The t(6;9) that characterizes a specific subtype of ANLL fuses the 3' part of a gene located on chromosome 9q34, CAN, to the 5' part of a gene located on chromosome 6p23, DEK. On the 6p- chromosome, the resulting DEK-CAN fusion gene is transcribed into a leukaemia-specific 5.5 kb chimaeric mRNA that encodes a putative DEK-CAN fusion protein. No transcription could be detected from the reciprocal CAN-DEK fusion on chromosome 9q+. Analysis of 17 t(6;9) ANLL cases showed that the translocation breakpoints occur in a single intron of 7.5 kb in the CAN gene (ICB9) and in a single intron of 9 kb in the DEK gene (ICB6). As a result, the presence of a t(6;9) in blood or bone marrow cells can be faithfully diagnosed by Southern blotting. Moreover, the result of the translocation is an invariable DEK-CAN transcript, which can be sensitively monitored by RNA-PCR. Surprisingly, a SET-CAN fusion gene was found in leukaemic cells from a patient with AUL. Like CAN, SET is located on chromosome 9q34, which explains the apparently normal karyotype of the leukaemic cells. The occurrence of a SET-CAN fusion gene indicates that CAN may be the relevant oncogene involved in leukaemogenesis, and that activation of CAN can be effectuated through fusion of its 3' part to either DEK or SET. As yet, the function of CAN, DEK or SET is unknown. None of the proteins shows consistent homology to any known protein sequences. However, preliminary localization data and analysis of sequence motifs suggested that DEK-CAN may have a role in transcription regulation. CAN contains several dimerization domains and a repeated motif that can function as an ancillary DNA-binding domain. DEK and SET are non-related proteins, but they share a stretch of acidic amino acids, which is also present in the fusion proteins. PMID- 1308168 TI - Cytogenetic and molecular analysis of chromosome 11q23 abnormalities in leukaemia. PMID- 1308169 TI - Philadelphia chromosome-positive leukaemia: the translocated genes and their gene products. AB - Overwhelming evidence indicates a role for the deregulated ABL protein tyrosine kinase in the aetiology of CML and Ph-positive acute leukaemia. These disorders are characterized by the generation of BCR/ABL fusion proteins with elevated tyrosine kinase activity. Although much is known concerning the transforming potential of ABL proteins in various systems, very little is understood of the normal function and mode of regulation of ABL activity. The mechanism of oncogenic activation is therefore also obscure. In spite of this, our understanding of the molecular details of these chromosomal translocations allows the design of therapies directed against their unique, leukaemia-specific proteins and RNA products. PMID- 1308170 TI - Connections between the retrosplenial cortex and the hippocampal formation in the rat: a review. AB - The retrosplenial cortex is situated at the crossroads between the hippocampal formation and many areas of the neocortex, but few studies have examined the connections between the hippocampal formation and the retrosplenial cortex in detail. Each subdivision of the retrosplenial cortex projects to a discrete terminal field in the hippocampal formation. The retrosplenial dysgranular cortex (Rdg) projects to the postsubiculum, caudal parts of parasubiculum, caudal and lateral parts of the entorhinal cortex, and the perirhinal cortex. The retrosplenial granular b cortex (Rgb) projects only to the postsubiculum, but the retrosplenial granular a cortex (Rga) projects to the postsubiculu, rostral presubiculum, parasubiculum, and caudal medial entorhinal cortex. Reciprocating projections from the hippocampal formation to Rdg originate in septal parts of CA1, postsubiculum, and caudal parts of the entorhinal cortex, but these are only sparse projections. In contrast, Rgb and Rga receive dense projections from the hippocampal formation. The hippocampal projection to Rgb originates in area CA1, dorsal (septal) subiculum, and post-subiculum. Conversely, Rga is innervated by ventral (temporal) subiculum and postsubiculum. Further, the connections between the retrosplenial cortex and the hippocampal formation are topographically organized. Rostral retrosplenial cortex is connected primarily to the septal (rostrodorsal) hippocampal formation, while caudal parts of the retrosplenial cortex are connected with temporal (caudoventral) areas of the hippocampal formation. Together, the elaborate connections between the retrosplenial cortex and the hippocampal formation suggest that this projection provides an important pathway by which the hippocampus affects learning, memory, and emotional behavior. PMID- 1308171 TI - Evidence for NMDA receptor involvement in environmentally induced dentate gyrus plasticity. AB - Research has demonstrated environmentally induced plasticity of hippocampal dentate gyrus-evoked potentials. Other research has shown a role of the NMDA receptor in dentate gyrus long-term potentiation (LTP). The authors tested the role of the NMDA receptor in one form of environmentally induced plasticity, in which transferring animals from their home cages to another environment results in significant excitatory postsynaptic potential (EPSP) enhancement and concomitant depression of the population spike. Rats were chronically implanted with stimulating electrodes in the perforant path and recording electrodes in the dentate gyrus bilaterally. Evoked potentials were recorded from freely behaving rats for four 20-minute sessions (1/wk), which took place immediately following an environmental transfer. Rats received 0.00, 0.05, 0.08, or 0.10 mg/kg MK-801 s.c. 30 minutes prior to recording sessions in either an ascending- or descending dose series. Results showed that MK-801 produced a reduction of the EPSP enhancement, which takes place over the 20-minute session. The effects of MK-801 on spike depression varied as a function of dose series and time within a session, suggesting a long-term effect of MK-801 on spike depression. There was no detected effect of MK-801 on behavior. Results suggest a role of the NMDA receptor in this form of environmentally induced plasticity with different effects of NMDA receptor antagonism on EPSP enhancement and spike depression. PMID- 1308172 TI - Linear relationship between the maintenance of hippocampal long-term potentiation and retention of an associative memory. AB - The hypothesis that the maintenance or decay of an associative memory trace after an extended retention interval is a function of the residual strength of the synapses originally strengthened during learning was examined in a classical conditioning paradigm in which high-frequency stimulation of a hippocampal input- the medial perforant path--served as a conditioned stimulus. Rats received perforant path stimulus-foot shock pairings while engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever pressing was the behavioral measure of learning and retention of the association. Stimulus trains to the perforant path at an intensity above the threshold for eliciting a population spike induced long-term potentiation of synaptic transmission in the dentate gyrus. Synaptic potentials recorded extracellularly in the dentate gyrus were subsequently monitored for 31 days to examine quantitatively the decay of synaptic potentiation, a period after which retention of the learned association was assessed. All rats learned the association to a similar extent and displayed equivalent amounts of long-term potentiation by the end of conditioning. A slowly decaying function of synaptic potentiation was observed in remembering rats, i.e., rats with high retention performance after the 31-day learning-to-retention interval, while forgetting was associated with a rapid decay of long-term potentiation. Behavioral performance at the long-term memory test was linearly correlated with the amplitude of long-term potentiation maintained just prior to the retention test. The results favor the hypothesis that long-term associative memory depends, at least in part, on the maintenance of elevated synaptic strengths in the pathway activated during learning and suggest a role for the lasting component of long-term potentiation in the maintenance of memory. PMID- 1308173 TI - Bilateral knife cuts to the perforant path disrupt spatial learning in the Morris water maze. AB - Both the hippocampus and the entorhinal cortex are known to be crucial for spatial learning, but the contribution of the pathway linking the two structures, the perforant path (PP), has never been tested in a spatial learning paradigm. The present study examined the role of the PP in spatial learning using the Morris water maze. Seven days after bilateral transection of the PP with a fine bladed knife, rats were habituated to the pool, then trained to swim from varying start locations to a platform submerged in a fixed location. After 28 training trials over 5 days, probe trials (without any platform present) were given to assess spatial memory for the location. Compared to sham-operated controls, lesioned rats showed slower learning and poorer asymptotic performance in terms of both swim path distance and escape latency, and less preference for the correct quadrant during probe trials. When the platform location was "reversed" to the opposite quadrant, the lesioned rats again showed poorer learning, poorer asymptotic performance, and reduced preference for the correct quadrant on the probe trial. When tested with a visible platform whose position varied from trial to trial, lesioned rats performed as well as controls. These results are congruent with previous analyses of the contributions of the entorhinal cortex and hippocampus to spatial learning and suggest that for spatial learning, the PP is a critical functional link between these two structures. PMID- 1308175 TI - Wait a minute, Jarrard and Davidson's data support configural association theory. PMID- 1308174 TI - Preserved configural learning and spatial learning impairment in rats with hippocampal damage. AB - This study was undertaken to compare the effect of hippocampal neurotoxic lesions in rats on two behavioral tasks, one a test of spatial learning, and the other an operant discrimination task that is acquired by forming nonspatial configural associations. Lesions of the hippocampus were made with microinjections of ibotenic acid. After postoperative recovery, rats were trained initially to locate a camouflaged escape platform in a water maze using distal spatial cues. Rats also were trained in the maze apparatus with a visible escape platform under conditions in which spatial information was made irrelevant to performance, i.e., cue learning. In an operant task, the same rats were then trained on a discrimination that included simultaneous feature positive and feature negative components (trial types XA+, A-, XB-, B+). After completion of this nonspatial configural learning task, rats received additional training in the water maze using a new platform location for spatial learning. To the extent that proficient performance in both the maze and operant tasks depends on a common function of the hippocampus, i.e., configural learning, the expectation was that hippocampal lesions would prove equally detrimental to performance in both tasks. Contrary to this expectation, lesioned rats were severely impaired in spatial learning but readily acquired the operant discrimination, even exhibiting some evidence of enhanced performance on this nonspatial configural learning task. Performance of the lesioned rats during cue training in the water maze was also enhanced relative to the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308176 TI - Support for configural association theory: now you see it, now you don't. PMID- 1308177 TI - Ultrastructural localization of neuropeptide Y-like immunoreactivity in the rat hippocampal formation. AB - Neuropeptide Y (NPY) has been implicated in the modulation of hippocampal neuronal activity and in the pathophysiology of several neurological disorders involving the hippocampal formation. Thus, this study examines the light and electron microscopic immunoperoxidase labeling of a rabbit polyclonal antibody against porcine NPY in single sections through each lamina of the CA1 and CA3 regions of the hippocampus and the dentate gyrus (DG) of normal adult rats. By light microscopy, the majority of perikarya with intense NPY-like immunoreactivity (NPY-LI) were located in stratum oriens of CA1 and CA3 of the hippocampus and in the hilus of the DG. Fine varicose processes with NPY-LI were found in all layers of the hippocampal formation, but were densest in the outer third of the molecular layer of the DG. The density of NPY-labeling was greater in the ventral portion of the hippocampal formation. By electron microscopy, most NPY-containing perikarya in all three hippocampal regions were: small (8-12 microns) or medium-sized (12-18 microns) and elongated; or medium-sized and round. A dense accumulation of NPY-LI was commonly observed within the individual saccules of Golgi complexes and some rough endoplasmic reticulum in the cytoplasm. Perikarya and dendrites with NPY-LI usually were directly apposed to other neuronal processes (mostly terminals) and lacked astrocytic appositions. The majority of terminals in contact with NPY immunoreactive neurons were unlabeled and synapsed with the shafts of large and small dendrites. In CA1 and CA3 of the hippocampus, the types of synapses formed by the unlabeled terminals were not significantly different; however, more asymmetric synapses than symmetric synapses were formed by the unlabeled terminals on the shafts of small NPY-labeled dendrites in the DG. The terminals with NPY-LI (0.25-1.2 microns) contained many small, clear vesicles and 0-2 large, dense-core vesicles. The types of synapses (i.e., asymmetric and symmetric) and distribution of NPY labeled terminals on the targets were remarkably similar in each lamina of the hippocampal subregions. The NPY-labeled terminals usually synapsed with one unlabeled perikaryon or dendrite. However, others synapsed either (1) with two unlabeled perikarya or dendrites simultaneously or (2) with one NPY-containing perikaryon or dendrite. Most of the terminals with NPY-LI formed symmetric junctions with the shafts of small (distal) dendrites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1308178 TI - Postnatal development of mossy cells in the human dentate gyrus: a light microscopic Golgi study. AB - Mossy cells in the human dentate gyrus of adults and children of different ages were impregnated using the rapid-Golgi method. In every case the cause of death was verified by autopsy and the brains were used when neither the history of the patient nor autopsy revealed brain-related disease. Mossy cells in the human share common light microscopic features with the same cell type in rats and monkeys. Their most characteristic feature is the extremely large and complex excrescences on their proximal dendrites. Distal dendrites display pedunculate spines. Mossy cells have a few somal spines. The axon of mossy cells originates from the cell body and gives rise to several collaterals in the hilar region. The axons could be followed for several hundred microns, but in only one case did an axon collateral enter the granule cell layer of the adult dentate gyrus. In the newborn child, mossy cells display immature somal and dendritic features. The soma frequently bear spines. The dendrites are varicose and terminate in presumed growth cones. Both proximal and distal portions of the dendrites bear a few pedunculate spines and long-irregular filopodia. A few small excrescences are present on the proximal dendrites. The first large, complex excrescences on the proximal dendrites of mossy cells appeared in the 7-month-old child. Both somata and dendrites display adult-like characteristics in mossy cells from a 5-year-old child. However, not all mossy cells are alike and some dendrites still display long filopodia. The axons of immature mossy cells were similar to adults. The present results indicate that connections between granule cells and hilar mossy cells of the human dentate gyrus develop through an extended postnatal period of time that may last until the fifth year. PMID- 1308179 TI - Time course and distribution of neuronal degeneration in the dentate gyrus of rat after adrenalectomy: a silver impregnation study. AB - Recently, Sloviter et al. reported that adrenalectomy (ADX) of young adult rats after 3 months led to a selective loss of granule neurons in the dentate gyrus (DG) and that this loss could be prevented by low doses of corticosterone. In the present study, the ADX-induced neuronal degeneration was investigated in Wistar rats, using a silver impregnation method for degenerating neurons. To examine the time course and distribution of the ADX-induced degeneration, young adult male rats were allowed to survive 2, 3, and 5 days and 1, 2, and 3 weeks after ADX. Argyrophilic neurons were present in the dentate granule cell layer on the second day following ADX. Three days after ADX, the number of argyrophilic granule neurons was much more abundant, and it increased gradually with longer post-ADX survival times. Argyrophilia was specifically confined to dentate granule cells and was accompanied by the occurrence of pyknotic nuclei as observed in adjacent cresyl violet-stained sections. There were significant differences between individual rats in quantity of argyrophilia. About one fifth of the ADX rats showed sporadic or no argyrophilia, in spite of plasma corticosterone levels below the detection limit (10 ng/mL). Sham-operated rats and ADX rats receiving corticosterone (10 mg/L) or dexamethasone (15 mg/L) in their drinking water did not display any argyrophilic neurons in the dentate gyrus. The distribution of the argyrophilia within the DG was highly characteristic with the highest number of degenerating cells in the hidden blade of the middle and the temporal thirds of the DG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308180 TI - Intact verbal and nonverbal short-term memory following damage to the human hippocampus. AB - Short-term memory was assessed in two groups of amnesic patients. Six patients had confirmed or suspected damage to the hippocampal formation, and six patients had diencephalic damage as a result of alcoholic Korsakoff's syndrome. Verbal short-term memory was evaluated with seven separate administrations of the standard digit span test in order to obtain a precise measure of short-term memory. Nonverbal short-term memory was evaluated with four tests that assessed apprehension, retention, and the ability to manipulate nonverbal material--all within the span of immediate memory. One of these four tests assessed short-term memory for spatial location. Patients with damage to the hippocampal formation had a digit span equivalent to that of control subjects and also performed normally on the four tests of nonverbal short-term memory. The patients with Korsakoff's syndrome had a marginally low digit span and performed poorly on three of the four nonverbal tasks, a finding consistent with the deficits in attention and visuospatial processing previously described for this patient group. These deficits are likely due to the frontal lobe atrophy typically associated with Korsakoff's syndrome, rather than to diencephalic damage. The results support the view that short-term (immediate) memory, including short-term spatial memory, is independent of the hippocampus. PMID- 1308181 TI - Navigation by fragment fitting: a theory of hippocampal function. AB - This paper describes a computational theory of spatial learning and navigation and its possible realization in the hippocampus. In the theory, mammals store memories of their geographical environment as a large number of independent fragments. A typical fragment denotes a few prominent landmarks in some region, their geometric relations, and their nongeometric properties, such as smells and visual cues. Navigation involves piecing together current sense data and relevant fragments to form a local map of the animal's surroundings; this is like solving a jigsaw puzzle. This computational model has been implemented in a computer program, whose performance is broadly consistent with observed levels of animal performance, and laboratory results, in spatial learning. Possible realizations of the model in animal brains are discussed. Unlike some neural net models of spatial learning, the model is strongly geometric, and uses special neural structures to store and manipulate two-dimensional vectors and bearings. A possible neural architecture is described in which the hippocampus performs the geometric operations; this has a long-term memory for fragments (somewhere in the neocortex), which can associatively recall fragments into a number of parallel fragment fitters, in the dentate gyrus and CA3 regions. These vary the positions and orientations of their fragments, to optimize the fit of the fragments to each other and to the animal's recent sense data. A local map of the animal's surroundings is stored in CA1 and subicular regions, where matching of fragment positions and attributes takes place. Mismatches are passed back via the entorhinal cortex to improve the fit during the next hippocampal theta cycle. The model offers the potential for understanding current data on spatial learning, on the neuroanatomy of the hippocampus and on place cells in a coherent framework, as well as understanding the role of the hippocampus in nonpositional memory tasks. Comparisons with experimental data are given. PMID- 1308182 TI - Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. AB - The CA3 network in the hippocampus may operate as an autoassociator, in which declarative memories, known to be dependent on hippocampal processing, could be stored, and subsequently retrieved, using modifiable synaptic efficacies in the CA3 recurrent collateral system. On the basis of this hypothesis, the authors explore the computational relevance of the extrinsic afferents to the CA3 network. A quantitative statistical analysis of the information that may be relayed by such afferent connections reveals the need for two distinct systems of input synapses. The synapses of the first system need to be strong (but not associatively modifiable) in order to force, during learning, the CA3 cells into a pattern of activity relatively independent of any inputs being received from the recurrent collaterals, and which thus reflects sizable amounts of new information. It is proposed that the mossy fiber system performs this function. A second system, with a large number of associatively modifiable synapses on each receiving cell, is needed in order to relay a signal specific enough to initiate the retrieval process. This may be identified, we propose, with the perforant path input to CA3. PMID- 1308183 TI - Comparison of the effects of ethanol and chlordiazepoxide on electrophysiological activity in the fascia dentata and hippocampus regio superior. AB - Acute intoxicating doses of ethanol-producing blood alcohol levels of 120-200 mg% increase paired-pulse (PP) inhibition in the dentate gyrus of anesthetized rats suggesting that ethanol increases recurrent inhibitory processes (Wiesner, J.B., and S.J. Henriksen (1987) Ethanol enhances recurrent inhibition in the dentate gyrus of the hippocampus. Neurosci. Lett. 79:169-173). To further understanding of the neuronal mechanisms underlying this phenomenon, the authors studied the effects of the benzodiazepine (BZ), chlordiazepoxide, and acute intoxicating levels of ethanol on extracellular field potential recordings and single-unit activity in the dentate gyrus and area CA1 of the hippocampus. In the dentate, ethanol had no effect on population excitatory postsynaptic potential (pEPSP) amplitudes or slopes; decreased population spike (PS) amplitudes (25%); increased PP inhibition; decreased dentate granule cell (DGC) spontaneous activity (58%); had no effect on putative interneuron spontaneous activity; and markedly increased post field potential-evoked interneuron discharges (IDs, 218%). Chlordiazepoxide had no effect on pEPSP amplitudes or slopes or PS amplitudes; increased PP inhibition; decreased DGC (62%) and interneuron (72%) spontaneous activity; and markedly decreased IDs (89%). In CA1, ethanol had no effect on pEPSP amplitudes or slopes; decreased PS amplitudes (26%); had no effect on PP responses; decreased pyramidal cell (PC) spontaneous activity (39%); had no effect on interneuron spontaneous activity; and markedly increased IDs (97%). Chlordiazepoxide had no effect on pEPSP amplitudes or slopes or PS amplitudes; had no effect on PP responses; decreased PC spontaneous activity (41%); and had no effect on interneuron spontaneous activity or IDs. The results suggest that the BZs decrease principal cell excitability by postsynaptic facilitation of inhibitory processes, whereas ethanol decreases principal cell excitability indirectly by increasing the excitability of inhibitory interneurons. PMID- 1308184 TI - Fast (beta) rhythms in the hippocampus: a review. AB - Spontaneous or evoked brain activity in the hippocampus showed a 20-70 Hz beta rhythm under some conditions, typically during behavioral activation and accompanied by a theta rhythm. Beta rhythms are generated locally, perhaps by a recurrent feedback loop involving pyramidal cells and inhibitory interneurons. Modulation of the local circuit and rhythm by cholinergic inputs has also been demonstrated. Under some behavioral states, neural impulses modulated at the beta frequency may transmit preferentially through the trisynaptic circuit in the hippocampus. It is suggested that the beta rhythm may serve to establish transient physiological connections, reflected in coherence at the beta frequency, among neurons in the hippocampus and related structures. Thus, the beta rhythm may play an essential role in hippocampal function. PMID- 1308185 TI - The importance of comparative studies and ecological validity for understanding hippocampal structure and cognitive function. AB - Building from the premise that hippocampal cognitive function has been molded by natural selection under natural environmental conditions, it is argued that traditional laboratory studies likely do not reveal the richness and complexity of hippocampal function. Research on the role of the hippocampal formation in the navigational behavior of homing pigeons is offered as an example to illustrate the advantages of using an ecological approach to understand hippocampal function. It is further proposed that dissimilarities in hippocampal anatomy, physiology, and neurochemistry found between species reflect species differences in the range of functions served by the hippocampal formation, as well as possibly the molecular and cellular mechanisms that support such functions. These differences notwithstanding, it is suggested that, from an evolutionary perspective, the primary function of the hippocampal formation is a role in some aspect of spatial cognition. Dissimilarities in hippocampal structure and function among extant species are viewed as resulting from differences in evolutionary selective pressure and evolutionary history. PMID- 1308186 TI - The mechanism of cerebral hypoxic-ischemic damage. AB - The four most prominent hypotheses on the cellular processes leading to hypoxic ischemic neuronal damage or death are (1) the lactacidosis hypothesis, (2) the calcium overload hypothesis, (3) the excitotoxic hypothesis, and (4) the oxygen free radical hypothesis. The authors comment on the evidence in favor of and against each in an attempt to select the one hypothesis that best explains the mechanism of cerebral hypoxic-ischemic damage while withstanding the scrutiny of scientific testing. A major part of this inquiry is derived from in vitro studies that are suited to mechanistic exploration. They conclude that the calcium overload hypothesis is the best qualified in this respect. It is important to note, however, that some of the other hypothetical mechanisms may play a secondary role in exacerbating neuronal damage by accelerating calcium influx and overload. PMID- 1308187 TI - Morphological evidence for altered synaptic organization and structure in the hippocampal formation of seizure-sensitive gerbils. AB - Seizure-sensitive (SS) and seizure-resistant (SR) Mongolian gerbils were used for three experiments. In the first experiment, GABAergic neurons and terminals in the dentate gyrus were localized with GAD immunocytochemistry. GAD-positive puncta adjacent to cell bodies of GABAergic pyramidal basket cells were counted in light microscopic preparations. The pyramidal basket cells of SS gerbils displayed a significant threefold increase in the number of GAD-positive puncta associated with their cell bodies as compared to those from SR gerbils. These data indicate that the number of GABAergic synapses with pyramidal basket cell bodies in the dentate gyrus was greater in SS gerbils. An electron microscopic (EM) analysis of GAD immunocytochemical preparations showed GAD-positive axon terminals forming symmetric synapses with GAD-positive basket cell bodies. However, numerous terminals forming symmetric axosomatic synapses with basket cells were not immunopositive, and other synapses formed by terminals were not classified because reaction product in the cell bodies obscured postsynaptic densities. Therefore, routine EM preparations were analyzed for symmetric and asymmetric axosomatic synapses on pyramidal basket cells and granule cells of SS and SR gerbils. The data obtained from these preparations showed that the pyramidal basket cells of SS gerbils had a selective increase in the number of symmetric synapses per 10 microns of soma as compared to those of the SR gerbils. In contrast, the granule cells did not show any significant difference in the number of either symmetric or asymmetric axosomatic synapses between SS and SR gerbils. These results indicate that pyramidal basket cell bodies of SS gerbils have more inhibitory synapses than do those of SR gerbils. The third experiment used SS gerbils with lesions of the perforant pathway that stopped seizure activity (Ribak, C. E., and S. U. Khan (1987) The effects of knife cuts of hippocampal pathways on epileptic activity in the seizure-sensitive gerbil. Brain Res. 418:251-260). The percentage of axon terminal area occupied by synaptic vesicles and their packing density was determined in CA3 mossy fiber boutons and compared for lesioned and nonlesioned SS gerbils. The mossy fibers of nonlesioned SS gerbils showed a depletion of synaptic vesicles consistent with the previous results of Peterson et al. (Peterson, G. M., C. E. Ribak, and W. H. Oertel (1985) A regional increase in the number of hippocampal GABAergic neurons and terminals in the seizure-sensitive gerbil. Brain Res. 340:384-389).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1308188 TI - Autoradiographic localization of proline uptake in excitatory hippocampal pathways. AB - An autoradiographic method was developed to localize sites of high-affinity, Na(+)-dependent proline uptake in the rat hippocampal formation. Hippocampal slices were incubated with [3H]proline, fixed with a glutaraldehyde/carbodiimide mixture, and cut into frozen sections. The sections were coated with photographic emulsion and autoradiograms were prepared. Autoradiographic grain densities were highest over the inner and outer thirds of the dentate molecular layer, followed by stratum lacunosum-moleculare of area CA3. Stratum oriens and stratum radiatum of area CA1 and CA3 were fairly intensely labeled. The pyramidal and granule cell body layers, stratum lucidum of area CA3, and middle third of the dentate molecular layer were lightly labeled. Effects of surgical and kainic acid lesions suggested that the lateral perforant path, associational-commissural fibers in the fascia dentata, and Schaffer collateral-commissural-ipsilateral stratum oriens fibers have considerable proline uptake capacity. In contrast, the medial perforant path and the mossy fibers appear to accumulate little or no proline. These results suggest that high-affinity, Na(+)-dependent uptake of proline is expressed by a subset of hippocampal glutamate pathways. The relative capacities of glutamate terminal populations to transport glutamate and proline varies widely. Proline was previously shown to possess neuroexcitatory and excitotoxic properties in the rat hippocampal formation. Taken together, these findings argue that proline plays a role in excitatory transmission. In elucidating this role, comparisons between medial and lateral divisions of the perforant path may prove especially advantageous. PMID- 1308189 TI - Monkey hippocampal neuron responses to complex sensory stimulation during object discrimination. AB - The purpose of this study was to investigate, during the performance of an object discrimination task, responses of neurons in the monkey hippocampal formation to the sight of several objects that have biological meaning, and compare these responses with those of amygdalar neurons studied previously using the same task. Neuronal activity in the hippocampal formation of conscious monkeys was recorded during performance of a task that led to presentation of familiar rewarding, familiar aversive, or unfamiliar objects. Of 864 neurons recorded in the hippocampal formation and adjacent cortices, 160 (18.5%) responded to the sight of a certain object(s). Responses to the sight of different kinds of objects were analyzed in detail. Nondifferential neurons (n = 73) responded to different objects with no significant difference in response magnitudes, and differential neurons (n = 87) responded to different objects with different response magnitudes. Of the differential neurons, 23 responded more strongly to rewarding objects than to other objects (rewarding-object-dominant neurons), but the magnitude of responses to objects did not necessarily correlates with the order of preferences to the objects as determined from observation of animal behavior. Aversive-object-dominant neurons (n = 13) responded more to aversive objects than to other objects. Unfamiliar-object-dominant neurons (n = 7) responded more to unfamiliar objects than to familiar objects. Selective neurons (n = 10) responded selectively to only one object or one category of objects. Fourteen of the rewarding- or averse-object-dominant neurons were tested in extinction or reversal trials. In 12 of 14 neurons, responses to a rewarding or aversive object did not change, or slightly weakened, in extinction or reversal trials. The results suggest the following. (1) Responses of rewarding- or aversive-object dominant neurons may be involved in object-reward or object-aversion association. However, responses of many of these neurons might reflect past inputs to reinforcement rather than extant emotional processing. (2) Responses of unfamiliar-object-dominant neurons may be involved in recognition of objects based on their familiar or unfamiliar aspects. These results are further discussed and compared with responsiveness of amygdalar neurons. PMID- 1308190 TI - Spatial responsiveness of monkey hippocampal neurons to various visual and auditory stimuli. AB - To investigate involvement of the hippocampal formation in spatial information processing, activity of neurons in the hippocampal formation of the conscious monkey was recorded during presentation of various visual and auditory stimuli from several directions around the monkey. Of 1,047 neurons recorded, 106 (10.1%) responded to some stimuli from one or more directions. Of these 106 neurons with directionally differentiating responsiveness, 49 responded to visual stimulation, 35 to auditory stimulation, and 22 to both. Among 81 neurons, each tested with more than 10 different stimuli, one type responded independent of the nature of the stimulus (nonselective, n = 39), and responses of the other type depended on the nature of the stimulus (selective, n = 42). To investigate effects of change in spatial relations between test stimuli and background stimuli fixed on the monkey or fixed in the environment, 59 of 106 neurons were tested while the experimental apparatus holding the stimulus was moved relative to the monkey. Of these 59 neurons, 36 changed their responsiveness; 7 maintained the magnitude of their responses but changed the response direction with the movement of the apparatus, 5 changed direction regardless of the movement, and 24 did not change direction, but decreased or extinguished responses from the preferred direction. Thirty-two of 106 neurons were also tested by rotating the monkey. The directionally differentiating responsiveness of 11 neurons followed the monkey (egocentric neurons), that of 9 remained in place in the environment (allocentric neurons), and responses of 12 were reversibly extinguished when the monkey was rotated. The results suggest that these hippocampal neurons may be involved in identification of relations among various kinds of stimuli in different spatial frameworks (egocentric or allocentric) and this identification may be developed from multiple sensory modalities. PMID- 1308191 TI - Neuronal activity in the hippocampus during delayed non-match to sample performance in rats: evidence for hippocampal processing in recognition memory. AB - Neuronal activity in the CA1 of rats was explored with regard to functional correlates of performance in an odor-guided continuous delayed non-match to sample task. Although different CA1 cells fired in association with each identifiable trial event, these analyses focused on cells that fired selectively during the period of odor cue sampling and response generation. The firing patterns of many of these cells reflected the match or non-match comparison between current and previous odor cues independent of the particular stimuli that composed those comparisons. Such cells were more prevalent in sessions when performance was highly accurate. Hippocampal cells did not demonstrate stimulus evoked firing that persisted through the memory delay, nor did they fire differentially to session-novel vs. repeated odor presentations. These results suggest that the hippocampus contributes to recognition memory by processing comparisons between current information and representations of previous stimuli stored in parahippocampal and neocortical structures. PMID- 1308192 TI - Which spatial behavior are we talking about? PMID- 1308193 TI - Development of synapsin I and synapsin II in intraocular hippocampal transplants. AB - Previous studies have indicated that the appearance of synaptic vesicle associated proteins known as the synapsins is one indicator of synapse formation. In this study, the levels and morphological distribution of synapsin I and synapsin IIa and IIb were studied in intraocular hippocampal transplants and in situ in the intact hippocampus. No detectable levels of either synapsin I or synapsin II were found in the fetal brain. The in situ levels of the synapsins exhibited parallel increases rapidly after birth, reaching peak levels at 8 weeks, after which a slight decline was noted in synapsin I and synapsin IIb. In hippocampal transplants, a comparable increase in the synapsins was seen during the first 8 weeks in oculo. It is likely that the synapse formation in the hippocampal transplants represents synapses from neurons within the transplant, as well as from various peripheral ganglia that send collaterals into the graft. Peripheral and central synapses express different synapsin I: synapsin IIa and IIb ratios. When the ratios of the synapsin proteins in hippocampal transplants were examined ratios essentially identical to those seen in the normal hippocampus were found, despite the numerous peripheral neurites innervating the grafts. Immunohistochemical studies supported the immunoblot data, showing no detectable immunofluorescence with synapsin antibodies in fetal or newborn hippocampal formation. The density of immunoreactive profiles increased substantially both in transplants and in the hippocampal formation in situ during the first 2 postnatal months. In conclusion, the present data demonstrate that hippocampal transplants in oculo can develop significant levels of the synapsins and that there is no time lag in development in these levels compared to the hippocampal formation in situ. PMID- 1308194 TI - Septotemporal variation of the supragranular projection of the mossy fiber pathway in the dentate gyrus of normal and kindled rats. AB - Previous studies have demonstrated regional variation in the anatomical organization and physiological properties of the hippocampus along its septotemporal (dorsoventral) axis. In this study, regional variation of the supragranular projection of the mossy fiber pathway in the dentate gyrus of normal and kindled rats was characterized with a scoring method for assessment of the distribution of mossy fiber synaptic terminals detected by Timm histochemistry. In normal rats, there was a sparse projection of the mossy fiber pathway into the supragranular region near the tips and crest of the dentate gyrus along the entire septotemporal axis, and a prominent projection into the supragranular region at the temporal pole. Kindling of the perforant path, amygdala, and olfactory bulb induced synaptic reorganization of the mossy fiber pathway into the supragranular region along the entire septotemporal axis of the dentate gyrus. There was regional variation of the seizure-induced synaptic reorganization along this axis, and distinct septotemporal patterns were observed as a function of the site of kindling stimulation. Kindling of the perforant path induced mossy fiber synaptic reorganization that was relatively more prominent in the septal pole than in the temporal pole of the dentate gyrus. In contrast, rats that received kindling stimulation of the amygdala had a more uniform distribution of synaptic reorganization along the septotemporal axis. As there is regional variation of the anatomical and physiological properties of the human epileptic hippocampus, these observations could be pertinent to human epilepsy. PMID- 1308195 TI - Maintained saturation of hippocampal long-term potentiation does not disrupt acquisition of the eight-arm radial maze. AB - The present experiment examined the anterograde effect of bilateral saturation of long-term potentiation (LTP) of the rat perforant path-granule cell response on acquisition of the eight-arm radial maze. To ensure maintained saturation, high frequency stimulation was applied to the perforant path immediately prior to each trial. LTP did not significantly increase the number of trials required for acquisition of the standard eight-arm radial maze task. Furthermore, the magnitude of LTP did not correlate with the rate of acquisition. LTP also did not significantly affect the number of either working or reference memory errors during subsequent training with only four of the eight arms baited; both control and LTP rats made significantly more reference memory than working memory errors, with the number of both types of errors decreasing as training progressed. These results indicate that prior saturation of LTP within the perforant path-dentate granule cell circuit does not affect acquisition of either the reference or working memory components of the radial maze task. The results are discussed in relation to the role of LTP in acquisition of the eight-arm radial maze. PMID- 1308196 TI - Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms. AB - Protein kinase C (PKC) comprises a family of kinases consisting of nine subspecies that are differentially distributed in the central nervous system. This implies distinct functions. Its involvement is suggested in cellular and molecular mechanisms by which the hippocampus exerts influence on information processing. In this study, it was questioned whether abnormal activity in the neuronal substrate, particularly the hippocampal formation, induced by amygdala kindling indeed impairs spatial memory performance and correlated alpha, beta I/II, and gamma PKC subspecies expression. Rats were trained in a spatial discrimination task (SDT) and simultaneously kindled in the amygdala to induce abnormal, epileptiform activity. Control rats were only trained in the holeboard, a "free choice" maze, in which working (WM) and reference memory (RM) were simultaneously examined. Halfway through and at the end of the experiments the influence of kindling and SDT training on the immunoreactivity for PKC subspecies alpha, beta I/II, and gamma was evaluated in the hippocampal formation. Kindling resulted in a gradual increase in afterdischarge duration and motor seizure (MS) severity. Repeated SDT training ultimately resulted in an asymptotic level of WM and RM performance. As soon as generalized MSs developed, kindled rats failed to improve RM, whereas WM was not influenced. Compared to untrained rats, in trained controls PKC gamma but not PKC alpha beta I/II immunoreactivity was elevated in CA1 pyramidal and dentate gyrus granular cells. Generalized but not partial MSs abolished these alterations in PKC gamma immunoreactivity. The present data indicate that repeated training in a SDT affects the expression of PKC subspecies gamma but not of alpha or beta in the rat hippocampus. Generalized epileptiform activity impair both acquisition of new spatial RM information and PKC gamma expression. It is argued that PKC gamma plays a role in cellular mechanisms through which pathological brain activity impairs certain aspects of spatial memory. PMID- 1308197 TI - Amygdala kindling-induced seizures selectively impair spatial memory. 2. Effects on hippocampal neuronal and glial muscarinic acetylcholine receptor. AB - The muscarinic acetylcholine receptor is linked via hydrolysis of phosphoinositides to the protein kinase C pathway. In a preceding paper (Beldhuis, H. J. A., H. G. J. Everts, E. A. Vander Zee, P. G. M. Luiten, and B. Bohus (1992) Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms. Hippocampus 2:397-410), the role of different isoforms of protein kinase C in neurobiological processes associated with plasticity was studied using both a spatial learning paradigm and amygdala kindling in the rat. This study extended the findings on protein kinase C activity to the level of the muscarinic acetylcholine receptor. Rats were trained in a spatial learning paradigm and kindled simultaneously in the amygdala to develop generalized motor convulsions. Control rats were trained only in the spatial learning paradigm to acquire stable working and reference memory performance. Alteration in the expression of the muscarinic acetylcholine receptor was investigated using a monoclonal antibody to muscarinic acetylcholine receptor proteins. Trained control rats that were exposed repeatedly to the spatial learning paradigm showed an increase in immunoreactivity for the muscarinic acetylcholine receptor located in the same hippocampal regions in which the protein kinase C activity was increased. In fully kindled rats, however, this increase located in principal neurons was absent, whereas expression of muscarinic acetylcholine receptor proteins was increased in hippocampal astrocytes. Moreover, fully kindled rats showed an impairment in reference memory performance as compared to trained control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308198 TI - Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. AB - Studies have shown that peripheral levels of corticosterone correlate with the magnitudes of two well-described physiological models of memory, long-term potentiation (LTP) and primed burst (PB) potentiation. In the present experiments, the authors investigated the effects of experimenter-controlled manipulations of the levels of corticosterone on the magnitude of hippocampal PB potentiation in urethane-anesthetized rats. Primed burst potentiation is a long lasting (at least 30 minutes) increase in the amplitude of the CA1 population spike and EPSP slope in response to physiologically patterned stimulation of the hippocampal commissure. The levels of serum corticosterone were controlled by implanting corticosterone pellets in adrenalectomized rats (ADX/PELLET). In the first experiment, a significant negative linear correlation between elevated (stress) levels of serum corticosterone (greater than 20 micrograms/dL) and the magnitude of PB potentiation in ADX/PELLET subjects (r = 0.60, P < .05) was found. In the second experiment, the shape of the corticosterone-PB potentiation function was different at low and intermediate levels of corticosterone than it was at high levels of corticosterone: There was a positive correlation at low levels (0-10 micrograms/dL), a peak response at intermediate levels (11-20 micrograms/dL), and a negative correlation at high levels (21-93 micrograms/dL) of corticosterone. Thus, the overall relationship between corticosterone and PB potentiation is an inverted-U function. These findings provide strong support for the hypothesis that corticosterone exerts a concentration-dependent biphasic influence on the expression of hippocampal plasticity. PMID- 1308199 TI - Phenytoin prevents stress- and corticosterone-induced atrophy of CA3 pyramidal neurons. AB - Repeated daily restraint stress and daily corticosterone administration to adult male Sprague-Dawley rats leads to decreases in the number of branch points and length of dendrites of CA3 pyramidal neurons of the hippocampal formation. This decrease is prevented by daily administration of the antiepileptic drug phenytoin (Dilantin), which is known to interfere with excitatory amino acid release and actions. Phenytoin had no obvious effect on behavior during and after stress and failed to prevent stress-induced reduction of body weight gain and stress-induced increases of adrenal weight relative to body weight; it also failed to attenuate glucocorticoid-induced diminution of the size of the thymus gland, indicating that it does not directly antagonize glucocorticoid actions. Stress- and corticosterone-induced effects on dendritic length and branch point number are more pronounced on the apical, as opposed to the basal, CA3 dendrites that receive the largest mossy fiber input from the dentate gyrus. Because phenytoin is also known to prevent ischemic damage, these results are consistent with a model in which stress- and corticosterone-induced CA3 dendritic atrophy is produced by excitatory amino acids released from the mossy fibers. PMID- 1308200 TI - Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique. AB - Previous attempts to elucidate whether a loss of hippocampal synapses occurs during aging provided conflicting results, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. This study was designed to reexamine the issue by means of modern technical procedures that provide unbiased estimates of synaptic numbers. Groups of 14 young adult (5 months old) and 14 aged (28 months old) male Fischer-344 rats were compared. Synapses were examined in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus, where synaptic contacts are predominantly formed by different systems of afferents, the entorhinal and commissural-associational fibers, respectively. The number of synapses per neuron was estimated with the aid of the stereological dissector technique. The results showed that the total number of synaptic contacts per neuron was significantly diminished in the MML (by 23.6%) and IML (by 22.7%) of aged rats relative to young adults. This age-related synaptic loss involved axospinous, but not axodendritic, junctions of the MML ( 24.4%) and IML (-24.0%). Both perforated and nonperforated axospinous synapses (distinguished by a discontinuous or continuous postsynaptic density, respectively) exhibited an age-dependent decrease in numbers, though this decrease did not reach statistical significance in the case of perforated junctions of the IML. The observed age-related loss of axospinous synapses may underlie the reduction in the amplitude of excitatory postsynaptic potentials and the decline in functional synaptic plasticity detected in the dentate gyrus of senescent rats. PMID- 1308201 TI - Structural synaptic plasticity associated with the induction of long-term potentiation is preserved in the dentate gyrus of aged rats. AB - Changes in synaptic numbers were examined in the hippocampal dentate gyrus of aged (28 months old) rats following the induction of long-term potentiation (LTP) by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 hour after the fourth stimulation. Stimulated but not potentiated and implanted but not stimulated rats of the same chronological age served as controls. Synapses were analyzed in the middle (MML) and inner (IML) molecular layer of the dentate gyrus. Using the stereological dissector technique, unbiased estimates of the number per neuron were obtained for the following morphological varieties of synapses: axodendritic synaptic junctions involving dendritic shafts, nonperforated axospinous synapses having a continuous postsynaptic density (PSD), and perforated ones distinguished by a fenestrated, horseshoe-shaped, or segmented PSD. The induction of LTP resulted in a selective increase in the number of synapses with segmented PSDs. This change was detected only in the potentiated synaptic field (MML), but not in an immediately adjacent one (IML), which was not directly stimulated during the induction of LTP. Comparison of these data with the results of our previous LTP study in young adult rats (Geinisman, Y. et al., 1991, Brain Res. 566:77-88) showed that the only significant difference in the absolute number of synaptic contacts per neuron between potentiated animals of the two chronological ages was an age-related reduction in segmented synapses of the MML. Relative increases in the number of segmented synapses per neuron were, however, virtually of the same magnitude in potentiated rats of both ages as compared with their respective controls. This finding may explain why senescent rats can be potentiated to the same extent as young ones. PMID- 1308202 TI - Partial rRNA sequences in marine yeasts: a model for identification of marine eukaryotes. AB - The V3 variable region of the large subunit rRNA was examined for nucleotide sequence signatures as potential taxonomic tools. Data are presented on 117 species, representing 23 genera of basidiomycetous yeasts. The results of nucleotide sequence alignments indicate that strains within species have identical base sequences and that species may differ from one another by one to more than 100 base positions. Phylogenetic analyses of the alignments indicates relationships among species, including the prediction of synonymous species and the clustering of species belonging to the Ustilaginales and Tremellales. These results suggest that species-specific nucleotide sequences can be used for the development of techniques for population analyses of a variety of marine and other microeukaryotes. PMID- 1308203 TI - Nucleotide sequence of the 18S ribosomal ribonucleic acid gene from two teleosts and two sharks and their molecular phylogeny. AB - The 18S rRNA sequence was determined for two teleostean fish species, Fundulus heteroclitus and Sebastolobus altivelis, and two sharks, Squalus acanthias and Echinorhinus cookei. To study the molecular phylogeny of these taxa, the sequences were compared with 18S rRNA sequences of the Coelacanth Latimeria chalumnae, the frog Xenopus laevis, and humans. Maximum parsimony analysis of the sequences resulted in a single most parsimonious tree that is in agreement with the expected phylogeny. The correct phylogenetic tree was also found when using S. altivelis alone as the teleost representative. In contrast, the most parsimonious tree found by using F. heteroclitus as the teleost representative presented anomalous groupings (the teleost branch being grouped with humans), matching results previously obtained. However, a bootstrap analysis showed that some branches containing anomalous relationships were not significantly supported. An explanation for this peculiarity, the differences between our tree and previously identified ones, and their phylogenetic implications are discussed. PMID- 1308204 TI - Direct sequencing of mitochondrial DNA detects highly divergent haplotypes in blue marlin (Makaira nigricans). AB - We were able to differentiate between species of billfish (Istiophoridae family) and to detect considerable intraspecific variation in the blue marlin (Makaira nigricans) by directly sequencing a polymerase chain reaction (PCR)-amplified, 612-bp fragment of the mitochondrial cytochrome b gene. Thirteen variable nucleotide sites separated blue marlin (n = 26) into 7 genotypes. On average, these genotypes differed by 5.7 base substitutions. A smaller sample of swordfish from an equally broad geographic distribution displayed relatively little intraspecific variation, with an average of 1.3 substitutions separating different genotypes. A cladistic analysis of blue marlin cytochrome b variants indicates two major divergent evolutionary lines within the species. The frequencies of these two major evolutionary lines differ significantly between Atlantic and Pacific ocean basins. This finding is important given that the Atlantic stocks of blue marlin are considered endangered. Migration from the Pacific can help replenish the numbers of blue marlin in the Atlantic, but the loss of certain mitochondrial DNA haplotypes in the Atlantic due to overfishing probably could not be remedied by an influx of Pacific fish because of their absence in the Pacific population. Fishery management strategies should attempt to preserve the genetic diversity within the species. The detection of DNA sequence polymorphism indicates the utility of PCR technology in pelagic fishery genetics. PMID- 1308205 TI - Isolation and characterization of an autonomously replicating sequence (ARSD) from the marine yeast Debaryomyces hansenii. AB - The marine yeast Debaryomyces hansenii is known to tolerate salinities ranging from 0 to 24%. As a first step toward the molecular analysis of halotolerance in this organism, we report the isolation of an autonomously replicating sequence (ARS) and its use in the construction of a shuttle vector. The ARS from D. hansenii (ARSD) is 0.4 kbp long, and the function rests in 0.13 kbp of the sequence. Sequence analysis of ARSD shows strong homology to ARS from other organisms, including a 12-bp consensus sequence common to all ARS functional in Saccharomyces cerevisiae. PMID- 1308206 TI - Chemical identification of catfish growth hormone and prolactin. AB - Isolation and primary structure of growth hormone (GH) and prolactin (PRL) from the pituitary gland of catfish (Ictalurus punctatus) are described. Alkaline extract of the pituitary glands was fractionated by gel filtration on Sephadex G 75, ion-exchange chromatography on DEAE-cellulose, and reversed-phase high performance liquid chromatography on Octadecyl silica ODS. Catfish GH and PRL were identified by Western blotting with antisera against chum salmon GH and PRL. The catfish GH consists of 178 residues and is the most similar to carp GH, with sequence identity of 77%, although there is an uninterrupted deletion of 10 amino acid residues that corresponds to carp GH (90-99). The PRL is composed of 187 residues, which also exhibits the highest identity (79%) with carp PRL. Sequence identity between catfish GH and PRL is only 27%. PMID- 1308207 TI - The use of the antiglobulin 'gel-test' for antibody detection. AB - Four antibodies used routinely in-house for the assessment of antiglobulin reagents (anti-Fyb, anti-Jka, anti-S) were tested in parallel using tube and antiglobulin 'gel-test' low ionic strength antiglobulin techniques. In the latter the red cells are centrifuged following incubation through a dextran matrix incorporating an anti-human globulin reagent. The results show that the antiglobulin 'gel-test' was less sensitive than the tube technique in the detection of these difficult antibodies. PMID- 1308208 TI - The gel test: some problems and solutions. AB - The gel centrifugation test (GT) is a method of transfusion serology, based on the fact that, after centrifugation, unagglutinated red blood cells (RBC) pass easily through a gel, while agglutinated RBC do not. The introduction of the GT to our blood bank transfusion routine [strictly following the manufacturer's instructions (DiaMed ID Micro Typing System)] resulted in problems with the interpretation of the results. These were overcome after the introduction of modifications, which included: (1) the systematic use of 1% RBC suspensions; (2) the use of 50 microliters of 1% RBC suspensions and 25 microliters of serum in all tests; (3) the control of all negative indirect antiglobulin tests (IAT) and direct antiglobulin tests (DAT) by the addition of 50 microliters of a 1% IgG coated RBC suspension followed by centrifugation; and (4) the systematic use of saline-suspended RBC for ABO typing in patients with positive DAT. PMID- 1308209 TI - The A1 (B) phenomenon: a monoclonal anti-B (BS-85) demonstrates low levels of B determinants on A1 red cells. AB - A monoclonal anti-B (BS 85) that reacts strongly with red cells from weak B variants (B3, Bint and Bv) has demonstrated the presence of a trace of B on A1 red cells. The agglutination of group A1 red cells by an anti-B antibody is called the A1 (B) phenomenon and is the converse of the B(A) phenomenon seen with certain monoclonal anti-A antibodies. Fragile A1 (B) agglutination is best seen by spin-tube techniques and A1 red cells negative in saline tests are agglutinated by albumin and protease enzyme-enhanced tests, but no reactions are seen with A2 red cells. The A1 (B) reaction is specifically inhibited by B substance, and D-galactose and the galactose-containing sugars melibiose and lactose. Red cells from B variants showed differential inhibition patterns with various sugars. A1 transferase levels were normal even in the strongest A1 (B) reactive blood samples, although the plasma H transferase levels and H status of these red cells were elevated. This is in contrast to the B(A) phenomenon which is associated with elevated levels of B transferase. It is suggested that A1(B) overlapping specificity can occur because of a combination of higher H activity (and thus more H sites) together with normal levels of A transferase activity as they are 20% higher than normal levels of B transferase. The production of anti-B reagents free of the A1 (B) phenomenon with BS-85 is achieved by suitable dilution using quality control tests with protease-treated A1 red cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308211 TI - Percy Lane Oliver, OBE (1878-1944): founder of the first voluntary blood donor panel. PMID- 1308210 TI - Proteolytic activity during storage of platelets in plasma. AB - Proteolytic activity was studied in platelet concentrates (PC) stored in plasma at 22 degrees C. In experiment 1, two PC with a higher (A) and a lower (B) white cell concentration were prepared from each of nine donors by centrifugation. Aliquots of the cell-free plasma, PPP, were stored as a control. Samples for the assay of fibrinopeptide A (FPA), elastase, spontaneous proteolytic activity (SPA), kallikrein-inhibiting activity, thrombin-antithrombin complexes (TAT) and D-dimers were collected initially and on days 1, 3, 5 and 7 of storage. Consumption of glucose, pH and concentrations of lactate dehydrogenase (LDH) and ATP were determined to investigate the metabolic status of the PC. The decrease in pH correlated to the leucocyte count, r = -0.74, P < 0.001 and to the increase in LDH, r = -0.74, P < 0.01. The levels of elastase and the SPA were consistently low in the PPP bags. In the PC elastase had increased by day 5 and the SPA by day 3; the levels in PC A were significantly higher than in PC B, P < 0.01. The leucocyte count correlated with the elastase activity, r = 0.71, P < 0.01, and with the SPA, r = 0.65, P < 0.01. A minor increase in FPA was demonstrated while no TAT and D-dimers could be detected. The cause of the formation of FPA was studied in experiment 2; three bags of PC and four of PPP were prepared from each of 16 donors. To the PC and three of the PPP bags either hirudin, aprotinin or no enzyme inhibitor (control) was added.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308212 TI - Fresh frozen plasma--opinion and evidence. PMID- 1308213 TI - Retention for a removable partial denture. AB - This article addresses the complex nature of retention in a removable partial denture. Retentive features range from magnets and springs to clips, clasps, and interfacial surface tension. The retentive quality of an extracoronal clasp varies with the alloy, physical form, location on the abutment, and positional relationship to other elements. Surveying to identify both occlusogingival and mesiodistal undercuts when the path of random dislodging forces are not definitely controlled is needed for effective retention. Augmentation of ineffective retention in existing clasps should concentrate on methods of deepening the undercut or increasing the suprabulge. Tightening of clasps already in contact with a tooth frequently produces adverse changes. PMID- 1308214 TI - Effects of labial margin design on stress distribution of a porcelain-fused-to metal crown. AB - PURPOSE: This study compared the stress distribution of three porcelain-fused-to metal labial margins on a central incisor under simulated occlusal force. MATERIALS AND METHODS: The margin designs were rounded-shoulder, rounded-shoulder with a bevel, and a chamfer. RESULTS: Evaluation of mean equivalent Mises tensile stress did not show any difference at the cement-dentin and metal-cement interfaces of the three margins. The mean equivalent Mises tensile stress at the porcelain-metal interface was found to be significantly higher for rounded shoulder when compared with the chamfer. There was no significant difference in the axial stresses along the three interfaces among the three margin designs. Statistically significant differences in radial stresses at some interfaces of the three margin designs were found. CONCLUSION: The change of cement thickness of the chamfer margin is significantly greater than that of either the rounded shoulder or the bevelled-shoulder margin. PMID- 1308216 TI - The effect of abutment angulation on stress transfer for an implant. AB - PURPOSE: This investigation compared the stress production characteristics of five abutment angulations for a specific implant system. MATERIALS AND METHODS: Photoelastic resin was cast directly to a 3.75 x 10-mm Branemark fixture (Nobelpharma USA, Inc, Chicago, IL) in a 50 x 70 x 13-mm mold. A strain gauge rosette was also incorporated in the resin to allow precise determination of normal stresses at a specific point. Each 4-mm abutment (15 degrees, 25 degrees, and 35 degrees from Implant Innovations (West Palm Beach, FL) and 0 degree and 30 degrees from Nobelpharma) was assembled on the fixture, subjected to 178N load, and viewed with a circular polariscope. Observed fringes were photographed and strain indicator readings were recorded. RESULTS: Mean observed fringe order and mean principle stress and strain at the location of the rosette were determined. CONCLUSION: At the location of the rosette, all five of the abutments produced principal strains (compressive and tensile) within the physiological zone for bone. The rosette was located approximately 4 mm away from the fixture. Higher stresses and strains can be expected in regions closer to the implant. PMID- 1308215 TI - The in vivo wear resistance of 12 composite resins. AB - PURPOSE: The in vivo wear resistance of 12 composite resins were compared with an amalgam control using the Latin Square experimental design. Sixteen edentulous patients wearing specially designed complete dentures formed the experimental population. MATERIALS AND METHODS: The Michigan Computer Graphics Measurement System was used to digitize the surface of the control and composite resin samples before and after 3-month test periods to obtain wear data. The 12 composite resins selected for this investigation based on their published composite classification types were seven fine particle composites, three blends, and two microfilled composite resins. The Latin Square experimental design was found to be valid with the factor of material being statistically different at the 5% level of significance. Wear was computed as volume loss (mm3/mm2), and all of the composites studied had more wear than the amalgam control (P = .001). RESULTS: After 3 months, the mean (error) of wear of the amalgam was 0.028 (0.006). Means (error) of wear for the 12 composites were ranked from most to least wear by mean wear volume loss. CONCLUSION: The absence of any relationship between mean wear volume loss and the volume percentage filler was confirmed by the correlation coefficient r = -0.158. PMID- 1308217 TI - Rates of osseointegration of dental implants with regard to anatomical location. AB - PURPOSE: Implantation of commercially pure titanium dental implants can be obtained predictably and consistently. The initial research focused on the edentulous population, with most of the fixtures being placed into the anterior mandibular area. There has been increased use of dental implants for partially edentulous patients. MATERIALS AND METHODS: This study reports the results of 169 consecutively treated patients with 673 fixtures. Patients were observed for 7 months to 8 years following occlusal loading. RESULTS: Implant osseointegration was 89.1% in the anterior maxillae; 71.4% in the posterior maxillae; 96.7% in the anterior mandible; and 98.7% in the posterior mandible. CONCLUSION: Osseointegration may be most dependent on anatomical location in the jaws. PMID- 1308218 TI - Compatibility of Type IV dental stone with polysulfide impression materials. AB - PURPOSE: In the American National Standards Institute/American Dental Association specification no. 19, compatibility of impression materials with dental stones is assessed by the presence of a 20-microns-wide line reproduced on an unmodified calcium sulfate dihydrate cast. In actual dental practice, modified type IV dental stones are used, although little is known of their compatibility with polysulfide impression materials. This study evaluated the compatibility of 6 polysulfide impression materials and 11 modified type IV dental stones. MATERIALS AND METHODS: A line 20 microns wide was etched on four glass dies. Four samples of each combination of impression material and dental stone were prepared according to the manufacturer's directions with an additional 3 minutes for the final setting time. Compatibility was determined by the presence of the reproduced line on the dental stones, as observed under low angle 10 x magnification by four rater groups. RESULTS: The line was reproduced on all of the impression specimens, and the examiners recorded 66 positive identifications of the line on the stone casts out of a possible 1,056 ratings for a total of 6.25% of the specimens. Out of a possible 66 impression-stone combinations, only 18 reproduced the 20-microns line. The combinations reproducing the lines most frequently (75%) were Neoplex with Blue Die Stone (Columbus Dental, St Louis, MO) and Coeflex with Indic Die Stone (Coe Lab Inc, Chicago, IL). CONCLUSIONS: The study showed that many combinations of polysulfide impression materials and modified type IV dental stones did not reproduce the 20-microns line; therefore, not every polysulfide is compatible with every type IV dental stone. PMID- 1308219 TI - The physiological effects of radiotherapy on oral tissue. AB - An increasing number of head and neck cancer patients are undergoing radiotherapy along or in conjunction with other treatment modalities. Radiotherapy extending over a period of weeks produces a variety of clinical manifestations. This article discusses the physiological changes that occur due to radiotherapy to elucidate the changes seen clinically. PMID- 1308220 TI - Screening for temporomandibular disorders: history and clinical examination. American Dental Association. AB - A temporomandibular disorder (TMD) conference was convened in 1982 by the president of the American Dental Association. One of the objectives was to develop guidelines for a brief screening history and examination relative to TMD in order to determine whether there is a need for a more comprehensive evaluation. Based on these guidelines and under the auspices of the American College of Prosthodontists, this article discusses a simplified TMD screening and examination form that requires minimum time for both the patient (history) and health care provider (examination) to complete. Succinct recommendations are also presented to enable the health care provider to quickly determine if a more detailed TMD history and examination are warranted. PMID- 1308221 TI - The dental curriculum: is is relevant to dental practice? AB - Does the undergraduate dental curriculum devote the appropriate amount of time to those areas of dentistry that are relevant to today's general dental practice? In a survey of dentists who graduated between 1980 and 1985, it was determined that they felt curriculum offerings in orthodontics, research, endodontics, periodontics, oral surgery, fixed prosthodontics, and occlusion had not been extensive enough. However, graduates also reported that their educational experiences in biochemistry, dental laboratory procedures, gross anatomy, microbiology, and occlusion were too extensive. PMID- 1308222 TI - The reporting of statistical inferences in selected prosthodontic journals. AB - Dental periodicals are the fundamental source of prosthodontic research. The ability to understand and contribute to dental literature is basic to the prosthodontic profession. The purpose of this study is to tally relative frequency with which various descriptive (n = 18), graphical (n = 7), and inferential statistical procedures (n = 68) are used in the prosthodontic literature. Our method consists of four procedures: journal selection, choice of 1987 through 1988 articles with inferential statistical content, tally of the statistical procedures in those articles, and quality control procedures used in obtaining these data. At least 50% of 10 prosthodontists selected 17 of 100 journals most likely to be read by prosthodontists. In the 17 journals, 1,320 articles were screened of which 406 were selected and evaluated for their statistical procedures. The bar and line plots were the most common graphical procedures occurring in over one fourth of the 406 articles. Percentages, means, and standard deviations occurred in more than 40%. Although 58% used the .05 significance level, only 0.3% mentioned power. Analysis of variance was used more often than the t tests (42% v 29%), whereas correlation/regression (21%) and chi square tests (14%) were used less often. The t tests, analysis of variance (Duncan, Tukey, and Student-Newman-Keuls multiple comparison procedures), chi square tests, correlation and regression, and the Wilcoxon tests occurred in at least 5% of the 406 articles. PMID- 1308223 TI - Titanium palate maxillary overdenture: a clinical report. AB - A clinical technique of using a cast titanium base in a maxillary overdenture for a patient with bruxism who has a history of repeated midline denture fractures is presented. The advantages of a metal palate and the favorable properties of titanium are discussed. This treatment provides the practitioner with a practical option for successfully treating difficult overdenture or conventional denture patients. PMID- 1308224 TI - Nontraumatic final impressions for fixed partial dentures. AB - A nontraumatic, nonretraction impression technique is presented which uses the fabrication of an acrylic resin shell from an interocclusal wax impression. A crucial step in the procedure is obtaining the complete finish line of the preparation within the resin. This tray, which is filled with an elastomeric impression material, is combined with a triple tray of the same material to provide all the necessary relationships to construct a crown or coping. This procedure is especially efficient for multiple abutments during fixed partial denture construction. PMID- 1308225 TI - Extraoral retention of an obturator prosthesis. AB - In this study, a technique is described by which large obturators can be retained with an acrylic resin head plate. The technique entails attaching the prosthesis to an acrylic resin plate with a 2-mm-diameter wire and then attaching the plate to the patient's forehead with skin tape. PMID- 1308226 TI - Fabrication of an obstructive sleep apnea prosthesis. AB - Obstructive sleep apnea, a sleep disorder, is becoming more prevalent and requires prompt and effective treatment by the dental and medical specialties. Conservative treatment modalities (ie, intraoral devices that prevent or minimize airway obstruction by the tongue) are recommended for treating mild to moderate forms of OSA. This article describes a simplified technique for fabricating an intraoral OSA prosthesis. PMID- 1308227 TI - The legal ramifications of AIDS. PMID- 1308228 TI - Alternative splint therapy for TMD. PMID- 1308229 TI - Long-term care insurance. PMID- 1308230 TI - Your retirement plan distribution. PMID- 1308231 TI - In defense of disinfection ... the handpiece study. PMID- 1308232 TI - Infant colic and maternal mental health: nursing research and practice concerns. AB - This study compared the mental health of 12 mothers who had infants with colic to 12 mothers of infants without colic. Colic was defined as infant fussing/crying of at least 2 hours/day for at least 5 out of 7 days, infant cry high-pitched and pain-sounding, and maternal report of infant inconsolability. Mental health was operationalized as scores on the Profile of Mood States and the Symptom Checklist 90R. Mothers of infants with colic had multidimensional psychological distress; they reported more bodily dysfunction, fears, disordered thinking, depression, anxiety, fatigue, hostility, impulsive thoughts and actions; and they had stronger feelings of personal inadequacy or inferiority. Implications for nursing research and practice are discussed in the context of study findings. PMID- 1308233 TI - Temperament and interactive effects: mothers and infants in a teaching situation. AB - Temperament is a theoretical concept used to understand individual's behavioral styles. In this study, temperament was measured in 13-month-old infants (N = 51) and their mothers, who were also observed together in a teaching situation. The purpose of the study was to determine the relationships between maternal and infant temperaments and interactive behaviors in the teaching situation. Mothers were given 10 minutes to teach infants four tasks designed to assess qualitative aspects of the interaction. In general, the interaction between mother and infant had a synchronous quality that was influenced by, but largely independent of, the temperamental characteristics of mother and infant. Responsive maternal teaching behaviors were significantly related to positive infant affect during teaching. Weak relationships were found between the temperament variables and interactive behaviors in the teaching situation. When mothers and infants were matched on temperament characteristics, no effects of matching temperaments on interactive behaviors in the teaching situation were found. These findings suggest that mothers are able to adjust their behaviors to compensate for their infant's temperament. Based on these data, nurses can focus on the dynamics of the interactions themselves and avoid making judgments based on temperament alone when evaluating mother-infant relationships. PMID- 1308234 TI - The relationship of attitudes, knowledge, and social support to breast-feeding. AB - Although more women are initiating breast-feeding, few continue for more than 1-3 months into the postpartum period. The current report studied the relationship of attitudes, social support, experimental and demographic variables, and knowledge to length of breast-feeding. A totaL of 102 women were included in the study and were followed for 1 year. Perceived attitudes toward breast-feeding, selected demographic variables, and past experiences were related to length of breast feeding. PMID- 1308235 TI - Cystic fibrosis: adolescent and maternal concerns about hospital and home care. AB - The purpose of this study was to describe problems occurring in adolescents with cystic fibrosis that related to home or hospital care, maternal concerns, and the role of the health-care professional in promoting care. Forty-question semistructured interviews of adolescents (N = 20) and their mothers (N = 12) were used. Interrater reliability (90%) was established through analysis of 8 audiotaped interviews and agreement on content analysis of the 32 interviews. Results are discussed according to five categories of concerns identified by adolescents: (a) knowledge deficits, (b) self-care/decision making, (c) home care management, (d) hospital care management, and (e) suggestions for health professionals. Mothers described six categories of concern: (a) fear, (b) effect on self, (c) disruption of family life, (d) health-care management at home, (e) health-care management in the hospital, and (f) suggestions for health professionals. PMID- 1308236 TI - The poet in Longfellow's 'Tales of a Wayside Inn': Dr. Thomas W. Parsons, 1819 1892. PMID- 1308237 TI - A clinico-pathologic presentation. Chemical chronic exposure to irritating material. PMID- 1308238 TI - Dentistry during the Golden Age of Islam. PMID- 1308239 TI - History of the dental department and oral and maxillofacial surgery department Boston City Hospital. PMID- 1308240 TI - Continuous force induced medial movement of the external auditory meatus and auricle. PMID- 1308241 TI - The power of positive doing as applied to practice management. PMID- 1308242 TI - In vitro evaluation of NaF and APF-gel application on surface microhardness of enamel in children of low, optimum and high fluoride areas. AB - An in vitro study was conducted on 78 sound human pre-molars collected from low (0.24 ppmF), optimum (0.7 ppmF) and known endemic fluoride areas (> 1.5 ppmF), to study the effects of topical application of sodium fluoride and APF-gel on surface microhardness of enamel of these three areas using Vickers microhardness measurements before and after application of topical fluorides at time intervals of 1/2 an hour, 6 hours and 24 hours. It was found that both the topical fluorides increased the surface microhardness of enamel in the three areas; the maximum increase in surface microhardness was observed in fluorosed teeth. APF gel was found to be more effective than sodium fluoride. PMID- 1308243 TI - Microleakage of composite-ionomer laminate restorations: an in vitro evaluation. AB - The in-vitro study undertaken on sixty teeth, 30 each of second primary molars and first premolars to evaluate the effectiveness of sealing property of composite-ionomer laminate restorations given on buccal aspects of these teeth after either Dycal base, ionomer base not etched and ionomer base etched indicated significantly more microleakage in dycal base composite resin restorations than composite ionomer. No difference in microleakage was seen in etched and unetched composite ionomer laminate restorations. Though microleakage was observed more in primary teeth than permanent teeth it was not found to be statistically significant. PMID- 1308244 TI - AIDS and hepatitis--some facts and practical methods for prevention of infection in dental operatory. PMID- 1308245 TI - Dentigerous cyst--an attempt to ascertain the normal eruption of involved tooth in child patient. AB - Dentigerous Cyst, in a young patient, located in the right palatal region, extending from 61 to 55, limited to the right side of mid-palatine suture and treated by marsupialization with post operative follow-up of 6 months has been reported. The involved permanent tooth (21) entrapped in the cyst was not extracted and found to erupt in normal direction. PMID- 1308246 TI - Taurodontism and pyramidal molars. AB - The present study was conducted to investigate the occurrence of taurodontism and pyramidal molars in Goa children, hitherto considered rare in Indians. Radiographs of 300 children of 9 to 13 years were evaluated. The criteria of Keene (1966) was used to designate taurodonts. Ten children showed taurodontism: involving mandibular second molars in eight cases, maxillary first molars in three cases; and pyramidal molars in three cases, four cases showed associated findings. Hypodontia of one to fourteen teeth was observed in all four cases. In addition one case showed thinning of maxillary central incisors, rotation of lateral incisors, impacted supernumerary and a canine and polydactyly of hands and feet. The condition does not appear rare in this population group. PMID- 1308247 TI - Use of sedation analgesia for pediatric dentistry. AB - 26 healthy children between the ages of 36 and 60 months (mean 35 months) who satisfied the selection criteria during a screening visit participated in this double blind study. The subjects were assigned randomly to receive either 75 mg/kg Triclofos elixir (Regimen I-21 children) or 50 mg/1kg Trichlofos elixir combined with 1 mg/kg promethazine elixir (Regimen II-22 children). All medications were given orally 45 minutes before treatment. During operative procedures all subjects received nitrous oxide/oxygen at a concentration of 35%. All the patients were restrained in a papoose board (Indigenous). The subjects were monitored for vital signs and evaluated for sedation and sleep, movement, crying and overall behaviour before, during and after the operative procedure. Regimen II was found to be superior to Regimen I with regard to behaviour management of difficult young children. However extremely apprehensive children were not good subjects for this sedation technique. PMID- 1308248 TI - Prevalence of thumb sucking in children of Calcutta. AB - The prevalence study of thumb digital sucking carried out on 3-12-year- old 2517 children, 1293 boys & 1224 girls, with different socio-economic status, belonging to villages, suburbs and city areas of Calcutta revealed that non-nutritional sucking habit was predominantly seen in cities, and bottle feeding was found to be the main cause of this habit; in 3-6-year-old children the prevalence of the habit was more in boys than girls but it persisted more in boys with increase in age. PMID- 1308249 TI - Interrelationship between sugar and dental caries--a study in child population of Orissa. AB - An epidemiological study on interrelationship between dental caries and sugar consumption conducted on 1265 children in the age of 5-15 years revealed a positive association of dental caries experience with total sugar exposures, between meal sugar exposures and at meal sugar exposures. As the total increased from 3 to 4 in a day, a corresponding jump of 1 deft+DMFT and 2 defs+DMFS was noted, which was clinically and statistically significant. It was deduced that total sugar exposures per day should be limited to 3, out of which two should be at meal time and one between meals. PMID- 1308250 TI - Evaluation of KAP of oral hygiene measures following oral health education through existing health and educational infrastructure. AB - This study is a part of a larger preventive oral health feasibility module embarked on a population of 120,000 of Raipurrani, district Ambala (Haryana). The KAP analysis of about 2000 individuals (including school children) on cross sectional basis at baseline, one and two years after the implementation of knowledge about oral health measures to the community utilizing the existing health infrastructure at CHC, the Anganwadi workers (ICDS Scheme) and through school teachers in the schools revealed that at baseline datun was the most prevalent (63%) oral hygiene measure used in the community and students. After implementation, the practice of brushing thrice, twice and once daily increased but the most prevalent frequency remained once a day (39% out of 66 percent using brush in community and 37% out of 76 percent in students after 2 and 11/2 years of implementation respectively) followed by twice a day (23 & 31% respectively). A similar pattern of frequency was observed about datun users also, though the number using datun substantially declined from 62% to 33% in community and 63 to 23% in students after implementation. PMID- 1308252 TI - Histochemical study on the gland of pelvis renalis in the horse. AB - The glands of pelvis renalis in adult and fetal horses were examined by histochemically. The glandular terminal was divided into two types, intraepithelial gland (IE) and extraepithelial gland (EE) by their locations and histochemical characters. Both glands were composed of mucous cells. The former lay in the transitional epithelium and were stained reddish with galactose oxidase-Schiff (GOS) and mild oxidation-Schiff (MOS), bluish purple with periodic acid-cold thionine Schiff-NaOH-PAS (PCP). The latter distributed in the lamina propria, but was not discovered in the fetus. They were stained weak or negative with GOS and MOS, reddish purple with PCP. Their difference of histochemical character might be reflect to chemical structure of the sialic acid. These mucous cells may cope with the urine contents as hippuric acid. PMID- 1308251 TI - An occupational hygiene survey in a Chinese viscose rayon factory. AB - The retinopathy (microaneurysm/small dot hemorrhage) is an early and specific biological indicator to quantitatively evaluate the CS2 exposure. The appearance of retinal lesions was observed among Yugoslavian, German and American workers exposed to CS2. However, among Finnish CS2 workers a positive result was not obtained. We suggested a different response to CS2 exposure between two ethnic populations. We had an opportunity to do a cross-sectional medical and occupational hygiene survey in a Chinese rayon staple plant. Cross-sectional medical examinations failed to show any chronic CS2 effects on the Chinese workers. PMID- 1308253 TI - Heterogeneity of monoclonal immunoglobulins with antistreptolysin-O activity detected in the cases of essential monoclonal gammopathy and multiple myeloma. AB - Two different types of monoclonal human immunoglobulins (M-components) with antistreptolysin-O (ASO) activity were investigated. The M-component FM with essential monoclonal gammopathy revealed to have an ASO activity, demonstrated not only by streptolysin-O neutralizing assay according to Ranz-Randall's method, but also by passive agglutination assays and precipitation on agar. The ASO activity was shown to reside in the Feb. These findings suggest that the M component FM have a true antibody activity. On the other hand, ASO activity of M component TT with multiple myeloma was detected only by streptolysin-O neutralizing assay, but the passive agglutinating assays and precipitation on agar showed no positive results. It has not been fully confirmed if the M component TT behaves as a true antibody activity. Heterogeneity of the M components with ASO activity was discussed. PMID- 1308254 TI - Higher sensitivity of the developing larvae of Angiostrongylus cantonensis than the adult worms to flubendazole and mebendazole. AB - Two kinds of benzimidazoles, flubendazole and mebendazole were each administered at 10 mg/kg to rats harbouring the developing larvae of the rat lungworm, Angiostrongylus cantonensis 3 or 10 days post-infection and to those harbouring the adult worms 70 days post-infection. Almost all of the larvae were eliminated from the rats mediated 3 days post-infection. The larvicidal effects of the drugs administered 10 days post-infection were not so high as those 3 days post infection. However, the growth of larvae in rats medicated 10 days post-infection were significantly inhibited as judged from their length, width and weight except the length of the larvae in rats given mebendazole. An inhibition of their growth was also demonstrated by the observation that no first-stage larvae were released from the rats medicated 10 days post-infection and examined 66 days post infection at which the first-stage larvae were released from non-medicated rats. On the other hand, when the drugs were administered 70 days post-infection, no effects were seen on the number, body size and weight of recovered worms, and the release of the first-stage larvae. A sound conclusion was drawn that the developing larvae are more sensitive to the drugs than the adult worms. PMID- 1308255 TI - Establishment and maintenance of bovine leukosis virus-free farm. PMID- 1308256 TI - Observations of Babesia gibsoni in midgut epithelial cells of the tick, Haemaphysalis longicornis. PMID- 1308257 TI - Inducing macrophagic potentials in cultured human lung fibroblasts. PMID- 1308258 TI - In vitro observation on egg release by Angiostrongylus cantonensis from rats treated with flubendazole. PMID- 1308259 TI - Immune recognition of human T-cell leukemia virus type-I (HTLV-I) by MHC restricted cytotoxic T lymphocytes. AB - In our studies, it was demonstrated for the first time that HTLV-I gag and pX, and env and pX antigens are the target antigens recognized by CD8+ CTL in association with RT-1k and RT-1l class I antigens, respectively, in the rat system. Furthermore, the gag-expressing rVV and the env-expressing rVV were shown to have the potential to induce HTLV-I-specific CTL in WKA and LEW rats, respectively. These results suggest that, in general, HTLV-I structural and non structural antigens can be recognized by CTL, and their immunogenicity for the induction of HTLV-I-specific CTL may be influenced by host MHC. Successful vaccination of mice against retrovirus tumorigenicity with the viral structural components has been demonstrated. As was the case with polyoma virus-induced tumors, utilization of rVV vectors containing HTLV-I genes for potential HTLV-I vaccines in humans may become possible if target antigens recognized by each recipient CTL can be identified prior to vaccination. Another vaccine candidate will be a synthetic peptide containing each CTL epitope. We are currently identifying the CTL epitopes, and recent results indicate that a major CTL epitope on the env-gene product is located between the env amino acids 101-112 (Tanaka et al., manuscript in preparation). PMID- 1308260 TI - TMJ arthroscopic surgery--new laser use. PMID- 1308261 TI - Oral conscious sedation for the pediatric dental patient. PMID- 1308262 TI - The effect of glucocorticoids on the development of murine granulocyte-macrophage (GM) progenitors. AB - The effect of glucocorticoids was tested on the hematopoietic system by assay of the ability of granulocyte-macrophage colony forming cells (GM-CFC) in mice to create GM colonies. The in vivo ability of bone marrow progenitor cells to granulocyte-macrophage colony formation was tested after long-term peritoneal glucocorticoids administration. The direct effect of these agents on cells in vitro culture was evaluated also. It was found that glucocorticosteroids inhibit the GM colony formation. The degree of damage to the bone marrow progenitor cells assaying by in vivo colony formation inhibition depends on the drug dosage and the length of therapy. The in vitro inhibition of granulocyte-macrophage colony formation depends on the concentration of the drug. The results suggest the possibility of the GM-CFC growth testing as an indicator of the side effects of prolonged corticoid therapy. PMID- 1308263 TI - Dietary cholesterol induced changes in serum lipoproteins in healthy females. AB - We studied the effect of high cholesterol fat breakfast containing approximately 527 mg cholesterol and 33 gm fat given for seven days in 10 healthy females of young age (18 to 21 years) and in healthy older females of age group (48 to 60 years). Serum total cholesterol and low density lipoprotein did not alter significantly after feeding and after withdrawal of high cholesterol fat breakfast. Serum high density lipoprotein increased significantly in young females after feeding and further increased after withdrawal for seven days, while in older females no appreciable change occurred. Serum triglyceride showed a significant decline in young persons after feeding but gradually increased after withdrawal while in older females no significant change occurred. PMID- 1308264 TI - Chronic cutaneous lupus erythematosus and subsequent infection with HIV1. AB - Since the beginning of the pandemia caused by the Human Immunodeficiency Virus several reports have described cases of infection by HIV1 in patients bearing rheumatic diseases. The infection by HIV 1 in patients with Systemic Lupus Erythematosus (SLE) and Chronic Cutaneous Lupus Erythematosus (CCLE), however, seems to be elusive. As far as we know, only 3 cases of HIV infection associated with SLE have been published. Furthermore, we have not been able to find out any report concerning HIV infection in patients bearing CCLE. The aim of the present article is to present a case of a female patient with CCLE that subsequently developed an infection with human immunodeficiency virus. PMID- 1308265 TI - A single preoperative dose of cefazolin versus postoperative amoxicillin and gentamycin combination in prophylaxis of orthopaedic and traumatologic surgery. AB - The use of antibiotic prophylaxis was evaluated in 228 surgical patients. The patients were given either cefazolin preoperatively or amoxicillin + gentamycin postoperatively in a randomized fashion to determine whether cefazolin would demonstrate an advantage over amoxicillin + gentamycin with respect to protection against postoperative wound infection, systemic infection and cost. We also tried to find out if the inflation of a tourniquet would interfere in the incidence of wound infection. Major postoperative wound infections were reduced in the cefazolin treated group (2.56 per cent versus 4.50 per cent). There also was a reduction in minor postoperative wound infections in the cefazolin group when it was compared with the amoxicillin + gentamycin group (6.83 per cent, 13.51 per cent, respectively). No systemic infection was seen in either group. There was no difference between the patients on whom were used tourniquets or not. Analysis of patients' charges suggested that 68.75% of the cost of preoperative antibiotic prophylaxis might be saved by limiting the duration of prophylactic drug administration by cefazolin. PMID- 1308266 TI - Thermal effect of glucose in women with normal carbohydrate tolerance: relationship to body mass index, blood insulin and noradrenaline. AB - Relationships between energy expenditure, body mass index (BMI), blood glucose (BG) responses to glucose ingestion were studied in 35 women aged 22-55 yrs with normal carbohydrate tolerance. In 13 of them plasma insulin (IRI) and catecholamine concentrations were also determined. Thirty seven per cent of patients did not respond to glucose load with an increased energy expenditure. In the remaining women the average thermogenic effect amounted to approx. 10% of their initial metabolic rate. A significant negative correlation (r = -0.415, n = 35, P(0.02) was found between BMI and the overall thermal effect of glucose (sigma TEG) calculated as a sum of the post-glucose energy expenditure measured every 15 min during 2 h minus the baseline value. Neither the fasting nor the post glucose BG concentrations correlated with sigma TEG. Significant correlations were ascertained between sigma TEG and the fasting IRI (r = -0.568), the sigma post-glucose IRI (r = -0.723), the ratio of sigma BG/sigma IRI (r = 0.845) and the post-glucose plasma noradrenaline concentration (r = 0.837). IN CONCLUSION: in women with normal carbohydrate tolerance the thermogenic effect of glucose depends to a large extent on insulin sensitivity and the glucose-induced activation of the sympathetic nervous system. PMID- 1308267 TI - Effect of ketamine on contractile performance of isolated frog myocardium and comparison of ketamine, thiopental and droperidol. AB - The influence of ketamine on the inotropic and chronotropic responsiveness of heart muscle was examined in spontaneously beating frog ventricular preparations. Ketamine produced a slight positive inotropic effect in isolated strips from the ventricle of the frog at 10(-5) M concentration. It does, however, possess negative inotropic properties at the higher doses studied (> or = 10(-4) M). Ketamine also decreased the heart rate of the ventricle at doses greater than 10( 4) M. Prior muscarinic blockade with atropine (10(-6) M) and histaminergic- H2 blockade with cimetidine (10(-5) M), did not affect the negative inotropic action of ketamine. Thiopental and droperidol also depressed the contractile performance of the frog myocardium. pD2 values of ketamine, thiopental and droperidol were found to be 3.44 +/- 0.63, 3.36 +/- 0.74, 4.18 +/- 0.45 respectively. These results suggest that the negative inotropic effects of ketamine is evident only at high concentrations and appears to be non specific. PMID- 1308268 TI - Cyclophosphamide effect on ultrastructural myocardial changes in rats on low magnesium diet. AB - Intraperitoneal cyclophosphamide administration to a total dose of 225 mg/kg body weight during six weeks produced in rat myocardial fibres evident focal degenerative changes in all organelles, and, fairly frequently, significant damage even up to necrosis. The experiment showed that in rats on low-magnesium diet cyclophosphamide produced more intense and more extensive changes than in rats receiving only cyclophosphamide. The extent of the lesions produced with low and high doses of cyclophosphamide was compared and it was observed that the lesions increased with an enlargement of doses of the drug. PMID- 1308269 TI - The histopathological comparison of the results of the intra-arterial injections of propofol and thiopentone in rabbits. AB - The results of injections of propofol and thiopentone intra-arterially are compared in rabbits according to histopathological criteries. Thirteen New Zealand type rabbits are used. Two ml of 2.5% Thiopentone and 2 ml of 1% Propofol are administered to the rabbits under anesthesia. Three days after, their ears are amputated and sent to this pathological blind examination. In both groups, we saw neither a morphological change along the vessel walls nor significant bleeding. But between the groups there was a significant difference about oedema. Consequently, 2.5% thiopentone which is routinely used after intra-arterial administration, may be responsible of the gangrenous change but it is discussable and it makes significant oedema in animal models although propofol does not have this effect. PMID- 1308270 TI - Role of pi form of glutathione S-transferase (GST-pi) in cancer: a minireview. AB - The pi class of the glutathione S-transferases is the most abundant of the human glutathione S-transferases family and is expressed almost in all tissues. However, the role of this protein is still poorly defined. It is suggested that this protein may serve as a marker for malignant transformation in some tissues. Additionally it seems that the phenomenon of tumour drug resistance may depend on the elevation of the glutathione S-transferase-pi. In this article we have attempted to review present knowledge concerning above problems. PMID- 1308271 TI - Gastrointestinal fistulas. AB - Gastrointestinal fistulas present a difficult problem to solve for the surgeons. Inspite of the recent progresses in diagnostic and therapeutic modalities, morbidity and mortality rates are still high. In this paper, we present our experiences on the postoperative gastrointestinal fistulas. We postulate that it is always better to prevent fistula formation rather than to cure it. PMID- 1308272 TI - Carcinoma oesophagus--an unusual cause of hypertrophic osteoarthropathy. AB - A rare case of Hypertrophic Osteoarthropathy in association with carcinoma of the oesophagus has been reported from Indian subcontinent. In addition to long bones short tubular bones are also involved in our case. Neurogenic theory is the most feasible pathogenesis for hypertrophic osteoarthropathy in the present case. PMID- 1308273 TI - Gastrocolic fistula due to gastric cancer (a case report). AB - Gastrocolic fistula originating from gastric cancer is a rare complication. Allison [1] collected 233 reports on patients with fistulas due to malignant tumours of the stomach and colon. In this article, a patient suffering from gastrocolic fistula as a complication of gastric carcinoma is presented. PMID- 1308274 TI - Extrapulmonary location of sarcoidosis. AB - Two cases of sarcoidosis located outside the lungs are reported. In both cases the symptoms of the sicca syndrome were in the foreground. In the first case other clinical manifestations included mediastinal and retroperitoneal lymphadenopathy, and lacrimal gland impairment. In the other case the symptoms of the sicca syndrome were associated with polyneuropathy and maculopapular skin rash. The diagnosis of sarcoidosis was confirmed by histological examination of a biopsy specimen of lower lip mucosa in the first case, and biopsy of skin lesion in the second case. Abnormal results of laboratory tests included only raised erythrocyte sedimentation rate, in both cases and presence of circulating immune complexes in one case. Serological tests failed to demonstrate the presence of rheumatoid factor, antinuclear and anti-ds DNA antibodies. No decrease was observed also in the haemolytic activity of the complement, and cryoglobulins were absent. Regression of clinical signs was obtained in both cases after treatment with glucocorticosteroids. PMID- 1308275 TI - Boleslaw Popielski and his priority in positive determination of 0 and A2 blood groups in biological trace materials. PMID- 1308277 TI - Analysis of association of peptic ulcer and essential hypertension from the standpoint of the problem of concomitant pathology. A possible role of vascular factor in the genesis of ulcer formation. AB - Patients with association of peptic ulcer and essential hypertension were found to form a heterogeneous group. Examination of this patients' group made it possible to distinguish certain clinical variants of such an association. Patients who first developed essential hypertension and then peptic ulcer were established to have a severe pattern of essential hypertension, unmarked and little symptomatic clinical picture of peptic ulcer, to be characterized by proneness to the complicated disease course. These features together with vascular lesions identified in the gastric submucosal layer, running their course as hypertonic microangiopathies permit attribution of the indicated ulcerations to the group of symptomatic gastroduodenal ulcers. In cases of association of peptic ulcer and essential hypertension, hemiton that suppresses the processes of gastric secretion was found to be the drug of choice. PMID- 1308276 TI - Henryk Jordan--on the centenary of Park Foundation. PMID- 1308278 TI - Controlling pollution of indoor office air. PMID- 1308279 TI - Case study of confined-space death illustrates need for written procedure. PMID- 1308280 TI - A complete written disaster plan helps maintain 'business as usual'. PMID- 1308281 TI - A big fight for small business. PMID- 1308282 TI - Will managed-care efforts help slow the runaway costs of workers' comp? PMID- 1308283 TI - [J. Monod, S, Spiegelman and enzymatic adaptation. Research programs, local cultures, and disciplinary traditions]. PMID- 1308284 TI - [History of the research on differentiating Hepatitis A and B]. AB - The numerous researches devoted to 'jaundice' during the Second World War have brought to light the existence of an infectious type of hepatic jaundice or 'homologous serum jaundice' following parenteral injection of vaccines containing human serum and blood transfusions, which were carried out on a large scale at the time. This type of serum jaundice was then gradually differentiated from 'catarrhal', contagious or epidemic jaundice by clinical trials along with large series of animal studies. Finally, the epidemiological, clinical and biological data obtained made it possible to establish, between 1944 and 1954, the viral etiology of these two types of jaundice: the A virus, present in the patients' blood and stools, was considered to be the agent responsible for epidemic hepatitis; the B virus, present primarily in the blood, was held to be responsible for serum hepatitis. PMID- 1308285 TI - [Treatment results of diabetes type 2 with obesity in the elderly]. AB - The aim of these investigations were the estimation of methods and results of treatment obese diabetics over 65 years and presentation of the most common mistakes of treatment. Two groups of elderly obese diabetics type 2 were compared. The first group involved the patients who kept closely to a low caloric diet and they achieved a decrease of their body mass. The second group consisted of the patients who failed to keep to a low caloric diet and their body mass after treatment either remained the same or increased. In almost all the cases of the first group a significant improvement was observed. The improvement manifested itself by the decrease of glycemia and glycosuria as well as by a lower demand for hypoglycemic drugs. In the second group the decrease of hypoglycemic drugs was not possible and in many cases the increase of hypoglycemic drug doses was necessary. The body mass reduction in obese diabetics also those of advanced years is a significant factor in the process of treatment and it is equally important to pharmacotherapy. PMID- 1308286 TI - [Influence of lovastatin on serum lipids in patients with primary hyperlipidemia and phenotype IIa and IIB. II. Changes of lipid composition of plasma lipoprotein fractions after lovastatin administration]. AB - In this study lipid composition of lipoprotein fractions LDL, VLDL and HDL was determined in 30 men with primary hyperlipoproteinemia phenotype IIa and IIb during lovastatin treatment. After 12 weeks of treatment in VLDL and LDL fractions decrease of percentage of cholesterol content and increase percentage of protein content was observed. The percentage of esterified cholesterol decreased in VLDL fraction and increased in LDL fraction during treatment. In HLP IIa significant decrease of percentage cholesterol content in VLDL and LDL fraction was observed. In HLP IIb decrease of percentage cholesterol content in VLDL and increase in percentage triglyceride content was found. Esterified cholesterol percentage decreased in VLDL fraction in HLP IIa. Lipids to protein ratio decreased significantly during treatment in VLDL and LDL fraction. The results of this study indicate that hypolipidemic treatment with lovastatin is associated with changes in lipid composition of lipoproteins, mainly with the decrease of percentage cholesterol content. PMID- 1308287 TI - [Changes in the level of certain hemostatic factors during treatment with lovastatin in patients with primary hyperlipoproteinemia and phenotype IIa and IIb]. AB - 12 weeks of hypolipidemic therapy with lovastatin in patients with primary hyperlipoproteinemia phenotype IIa (20 persons) and IIb (10 persons), apart from decrease of serum total cholesterol, LDL-cholesterol and apolipoprotein B concentration caused significant decrease of antithrombin III, plasminogen and Factor VII activity. The mean decrease in antithrombin III activity (from 103.5 to 91.7% in HLP IIa and from 97.3 to 85.4% in HLP IIb) was significant in both groups, decrease of Factor VII activity (from 111.9 to 100.1%) was significant in HLP IIa and decrease of plasminogen (from 101.9 to 90.6%) in HLP IIb. There were no changes in fibrinogen concentration, prothrombin, Factor VIII activity and aPTT during treatment. Significant correlations of changes in blood lipids and changes in hemostatic factors after treatment were observed. The results of this study indicate that changes in blood lipids during hypolipidemic therapy are associated with significant changes in hemostatic factors. PMID- 1308288 TI - [Treatment results in patients with mitral valve disease in IV functional class of NYHA. I. Surgical treatment]. AB - In the group of 142 patients with mitral valve disease (61% in IV and 39% in III functional class of NYHA) the efficacy of mitral valve replacement (MVR) was analysed. In all of the patients clinical, noninvasive and invasive investigations were obtained and compared before an after surgery. After MVR a statistically significant differences (p < 0.05 or p < 0.01) of RHV, noninvasive and hemodynamic data was observed. The survival during ca 1836 days after surgery of patients in IV class of NYHA was 72%. The improvement of activities correlated well with changes of functional class of NYHA. PMID- 1308289 TI - [Treatment results of patients with mitral valve disease in IV functional class of NYHA. II: Conservative treatment]. AB - In the group of 60 patients with mitral valve disease (67% in IV and 33% in III functional class of NYHA) the efficacy of medical treatment was analysed. In all of them clinical, noninvasive and invasive investigations were obtained. The conclusion is that survival during ca 1643 days was 15% of the patients in IV class of NYHA. The death was mostly due to severe heart failure. PMID- 1308291 TI - [Alcohol and hypertension]. PMID- 1308290 TI - [Fetal fibronectin as a predictor of threatening preterm delivery]. AB - The presence of cervicovaginal fetal fibronectin in the second and third trimesters of pregnancy identifies a subgroup of women are at high risk for preterm delivery. This phenomenon may reflect the separation of the chorion from the decidual layer of the uterus with release of fetal fibronectin into the cervical and vaginal secretions. PMID- 1308292 TI - [Biliary tract cysts and their treatment]. PMID- 1308293 TI - [Acid-peptic disease associated with Helicobacter pylori in children. Report of a case]. PMID- 1308294 TI - [Surgical revision and correction of choledochal cysts]. AB - Choledochal cyst are a rare congenital abnormality, seldom treated by the General Surgeon. We report six cases of re-operation found on a eighth year period. Six cysts type I, and one type II (Todani's Classification) were found. On five of them, an internal derivation had been performed, in one patient only a celiotomy was performed, and in another one a colecistectomy. Complete resection of the cyst was performed in six cases. In one female patient, this was impossible, because a carcinoma was found, she died postoperatively. We recommend external bile duct drainage for those cases where a complete resection can not be performed. This option alleviates the symptoms, allows morphological studies and do not compromise the final procedure which must be the complete excision of the cyst. PMID- 1308295 TI - [Surgical treatment of biliary lithiasic disease in elderly patients]. AB - A transversal retrolective analysis of all patients undergoing surgical treatment for cholelithiasis and choledocholithiasis between 1980 and 1987 was performed. The aim of the study was to investigate risk factors for the development of postoperative complications and mortality in elderly patients. A group of 187 patients above 70 years old were comparatively analyzed with 962 younger patients (total group: 1,149). Medical records were evaluated with emphasis to the diagnosis, associated diseases, characteristics of the surgical treatment, postoperative complications and mortality. Fifty percent of the elderly patients presented one or more concomitant diseases which significantly contributed to their operative risk. Acute cholecystitis, choledocholithiasis and cholangitis were more frequently found in aged patients (p < 0.05). In this group more patients also required bile duct exploration (p < 0.005). Major complications occurred in 16% and nine developed wound infection (5%). Operative mortality was 5.3%. In contrast, operative mortality of patients under 70 years of age was 1.5% and postoperative complications occurred infrequently. Acute cholecystitis, congestive heart failure, a history of myocardial infarction, and liver insufficiency were found as specific risk factors in the elderly. PMID- 1308297 TI - [Usefulness of clinical, radiologic, and endoscopic studies in chronic diseases of the terminal ileum: analysis of 36 cases]. AB - With the purpose of defining which is the most frequent chronic pathology of the terminal ileum in a reference center (INNSZ), and establish the diagnostic accuracy of the preoperative procedures used, 36 resection specimens were reviewed histopathologically. The diseases found in decreasing frequency were: Crohn's disease, tuberculosis, carcinoids, lymphomas, endometriosis and leiomyomas. Seventy-seven percent of the cases were benign and the rest malignant. The number of cases in which the preoperative diagnosis was right or included among the differential diagnosis was as follows: clinical study 44%, radiological study 48%, endoscopical study 32% and histological study by means of endoscopic biopsy 20%. The most frequent differential diagnosis were Crohn's disease, tuberculosis and intestinal lymphoma. It is concluded that chronic disease of the ileum represents frequently a diagnostic problem due to their clinical, endoscopical and radiological similarities which may only be solved by histological analysis of the surgical specimens. PMID- 1308296 TI - [Usefulness of the 14C-urea marked test in the detection of Helicobacter pylori in patients with dyspepsia]. AB - This study was undertaken to evaluate the usefulness of the urea test (UT) in the detection of Helicobacter pylori (HP) in dyspeptic patients. The UT was done in 105 patients with dyspepsia who underwent endoscopy and biopsy. Hematoxylin-eosin and Warthin Starry tissue stains were performed for HP detection, and the resulting microscopic findings were considered as the gold standard. The sensitivity, specificity, and positive and negative predictive values of the UT were of 95%, 63%, 85% and 83% when compared to the hematoxylin-eosin stain related findings, and 99%, 79%, 93% and 96% when compared to those related to the Warthin Starry stain. We conclude that the UT is a simple, non-invasive and useful diagnostic alternative to detect HP in patients with dyspepsia. PMID- 1308298 TI - [Littre's hernia with appendix in its contents. Presentation of a case]. AB - Littre's hernia is defined as any hernial sac which contains a Meckel's diverticulum. It has been reported in association with inguinal or femoral hernias principally and this hernia is rare but well described. A case is reported of a 44 years old man programmed for repair of a right inguinal hernia and we found incidentally that the sac contained a Meckel's diverticulum and the appendix. We reviewed the literature about this pathology and comment the management. It is concluded that the best management of Meckel's diverticulum is intestinal resection and the hernia, where the diverticulum was found, should be repaired. PMID- 1308299 TI - [Physico-chemical properties of ursodeoxycholic acid and its usefulness in hepatopathies]. AB - The authors of this article reviewed the physico-chemical properties of bile acids, with particular attention to ursodeoxycholic acid. Based on this information they explain the rational for treating some chronic liver diseases, like primary biliary cirrhosis and primary sclerosing cholangitis with bile acids. Finally they discussed the results of the different clinical trials of ursodeoxycholic acid in chronic liver diseases. PMID- 1308300 TI - [Knowledge, application, and diffusion of results of clinical research: the case of porto-systemic encephalopathy]. AB - The objectives of this survey were to evaluate the medical knowledge, acceptance and application of research results, and to identify the main sources of information in our environment. Portal-systemic encephalopathy (PSE) was the specific health problem addressed. Three hundred seventy-seven attendants to the National Mexican Gastroenterology Week (december 14-19, 1991) were surveyed. The results point out: 1) Gaps in PSE knowledge, since 30% or more incorrect answers were obtained for some PSE manifestations and therapeutic measures; 2) A persistent use of measures with doubtful efficacy, which is exemplified by the regular use of neomycin by (80%) of the respondents, 3) frequent influence of the availability of therapeutic measures (68%), as the satisfaction with therapeutic response (66%) on PSE treatment patterns, and 4) important role of continuing education courses and/or scientific meetings (> 66%) and medical journals (> 57%) as sources of information. PMID- 1308301 TI - [Laparoscopic surgery: the latest fashion?]. PMID- 1308302 TI - [Cancer of the pancreas. What is going on in our country?]. PMID- 1308303 TI - [Hepatic surgery: 10 year experience at the Salvador Zubiran National Institute of Nutrition]. AB - Techniques for surgical liver resections have improved in the last years. The results obtained with liver resections in 67 patients with benign and malignant tumors in a referral hospital for liver diseases in Mexico are analyzed retrospectively, with the aim of knowing the results obtained with such problems in our country. For benign diseases we operated on 36 patients with mean age of 45 years (26 were women), we had one operative death. In 31 patients with operations for malignant tumors (16 were primary liver tumors), the mean age was 52 years and 17 were men; there were eight operative deaths. Major hepatic resections are justified, the results are very satisfactory in benign disease; a major proportion of complications have to be accepted in patients with malignant disease; however, the results are good if we realize that those patients will die in few months if the tumor is not removed. PMID- 1308304 TI - [Laparoscopic cholecystectomy. Analysis of 50 cases]. AB - Biliary lithiasis is considered a significant health problem. Traditionally open cholecystectomy has been considered the gold standard procedure for symptomatic cholecystitis. Laparoscopic cholecystectomy has recently emerged as an alternative, but its usefulness in community hospitals is still being evaluated. Herein we reported our experience in 50 patients treated for 7 months (August of 1991, to February of 1992) by laparoscopic cholecystectomy. It has been necessary to convert one case into an open surgery. There has been no mortality. Seven patients developed right shoulder pain postoperative, it was controlled with minor non addictive analgesics. One had umbilical hematoma, another patient had a superficial phlebitis, and another one developed urinary retention. 43 patients (86%) had had 12 to 24 h hospital stancy, and were back to their normal activities in 7 days; during a 7 months follow-up no complications have been reported. We concluded that laparoscopic cholecystectomy is a safe procedure and can be done by the average general surgeon in community hospitals in a selected patient population. However, we strongly support a continuous monitoring of a protocol for patient management for record-keeping-purposes and as an educational tool. PMID- 1308305 TI - [Diazepam versus midazolam as pre-endoscopic medication]. AB - A prospective randomized double blind study was carried out on 60 patients undergoing elective gastrointestinal endoscopy. Patients in group A were sedated with diazepam (0.15 mg/kg) and those in group B received midazolam (0.10 mg/kg). There were no differences between the groups in age, sex, previous drug intake, level of anxiety prior to the procedure and from the endoscopist point of view the easiness to perform the studies. The group of patients who received midazolam (B) showed a significantly greater sedation, had less pain in the site of injection, their retrograde amnesia was more effective and tolerated much better the overall procedure (p < 0.05). There were no complications in either group. The cost per dosage was 2:1 greater with midazolam. It is concluded that midazolam has some advantages over diazepam used for sedation of patients undergoing gastrointestinal endoscopy. The time for recovery and cost are its disadvantages. PMID- 1308306 TI - [Phlegmonous colitis]. AB - Phlegmonous inflammation of the digestive tract is a rare lesion related in the majority of the previously described cases to systemic infections and chronic hepatic diseases. Both process may promote gastric and intestinal loss of the mucosal local defenses mechanisms against bacterial invasion. The term phlegmonous enterocolitis or gastritis defines an acute inflammatory process with purulent or nonpurulent character, that selectively damages the gastric, small and large intestines submucosal layer. The intestinal lesions are more frequently located in the small portion, followed by the colonic involvement. In the present paper we describe the postmortem findings and clinical course of a case with phlegmonous colitis in a 53 years old woman with cirrhosis and S pneumoniae septicemia. PMID- 1308307 TI - [Endoscopic resolution of acute dilatation of the colon secondary to edema of colonic anastomosis]. AB - Acute colonic dilation due to anastomotic edema is rare and is not always solved with conservative treatment. Endoscopic colonic decompression was carried out in 3 patients completing the procedure with a transrectal drainage. No complications resulted from the procedure and all 3 patients did well, once motility was re established. PMID- 1308308 TI - [Pancreatic resections at general hospitals in Torreon, Coahuila]. AB - A retrospective study of nine patients with pancreato-biliary neoplasias were operated in several general hospitals in Torreon, Mexico. Six had pancreatic adenocarcinoma, two ampullary carcinoma and one with common bile duct benign adenoma. We had a morbidity of 55% (5/9); three cases with pancreatic fistula (resolved with nutritional support and general measures) two had obstruction of gastricyeyuno anastomosis (one required surgical management). One patient (11%) died of massive pulmonary embolism. We have now the possibility to perform an earlier diagnosis with update invasive and non invasive diagnostic studies such ERCP, computed tomography and angiography. We are proud to have in our hospitals, intensive care units and well trained surgeons that allow us to perform such kind of specialized surgery. PMID- 1308310 TI - [Vertigo and bites]. PMID- 1308309 TI - [Endoscopic ultrasonography in gastroenterology: its clinical relevance]. PMID- 1308311 TI - Contrast sensitivity in clinical practice. AB - We collected and evaluated the results of contrast sensitivity (CS) examination by means of Vistech chart with an arranged testing distance 208 and 420 cm covering spatial frequencies 1.15-27.25 cycles/degree (c/deg). Our test was comprised of normal population and patients with chronic renal insufficiency including the group of waiting patients, dialysed patients and dialysed patients after neuroretinopathy and also patients after kidney transplantation and those with Alport's syndrome. We gave our attention to the results of visual acuity (VA) and contrast sensitivity (CS) examination in patients after surgery for detached retina, aphakic patients and patients with artephakia. We examined and evaluated CS in patients with intraocular hypertension. All patients reached the VA values 6/9-6/6. 1. The results of examination of 100 healthy persons of different age displayed significant differences in age groups covering all spatial frequencies between the groups 21-50, 51-60 and 61-80 years whereas in sets of higher age we registered differences in the region of medial spatial frequencies only. These data served us to create control groups in the individual partial groups. 2. Patients with chronic renal insufficiency have CS significantly lowered. These examinations suggest that there is a certain relation between renal and retinal functions and that the dialyzation treatment is not able as yet to compensate fully all changes evoked by renal insufficiency. A clear tendency to normalize CS after renal transplantation is suggestive of a certain reversibility of these changes. This is valid for transplant patients with a clear lens. If opacity of the posterior cortex of the lens occurs after a long-time cortisone treatment, a substantial fall in the CS curve is registered in all spatial frequencies in spite of the VA being 6/9-6/6. Patients with neuroretinopathy have CS always significantly disturbed. These changes are reversible although this reversibility is not complete. The new way of dialyzation treatment secures a relatively rapid normalisation of pathological changes in the fundus and repair of subjective functions. At the same time we came to the conclusion that the prognostic outlooks of these patients have become distinctly better as far as their subjective visual functions are concerned. 3. Patients after surgery for detached retina displayed in all cases in the operated eye highly reduced CS in median and low spatial frequencies simultaneously with a statistically significantly lower threshold visual acuity and reduced slope of the acuity function in the diseased eye.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1308312 TI - Our experience with management of epiphyseolysis in children and adolescents. AB - A total of 58 children is referred to with fractured growth plates of the distal forearm, proximal humerus, radial condyle of humerus, ulnar epicondyle of humerus, distal tibia, proximal tibia and the distal femur. The related injuries are divided in accord with Salter-Harris classification. The treatment of epiphyseolyses is concerned together with summarizing its results and the appropriate experience. In addition, the indications for both conservative and surgical approaches are delimitated in treating these injuries. PMID- 1308313 TI - Surgical treatment of vesico-renal reflux in children aged up to 3 years. AB - A total of 36 children age-ranged from 2 up to 34 mos (17 boys and 19 girls) with previous surgery for the vesico-renal reflux has been evaluated. This disorder had most commonly been classified to be of higher degree (IV. and V. 45%) and often showed no response on repeated conservative treatment with even stronger antibiotics. The boys (27 ureters) and girls (31 ureters) underwent the 32 antireflux operations after Anderson-Glenn and those 26 after Politano Leadbetter, respectively. In 6 ureters, their resection and modelling after Hendren was necessary to be done. On post-operative check-out, the 6 post antireflux Anderson-Glenn's plastic ureters revealed on miction cystography the persistent vesico-renal reflux re-operated subsequently in accord with Politano Leadbetter. From them, in 2 ureters the post-operative stricture has occurred in the site of ureter-to-bladder healing that was transitorily secured with percutaneous nephrostomy. PMID- 1308314 TI - Reconstruction of the penis following necrosis from circumcision used high frequency cutting current. AB - Penis necrosis secondary to circumcision by an electrical scalpel in a 2 years and 2 months-old boy occurred. After healing of the electric burn only stumps of the erectile bodies and strictured urethral meatus remained. The penis shaft reconstruction by corpora mobilisation and by detachment of the crura from the pubo-ischial rami was effected. This procedure gained 6 cm of a new length of the penis. To prevent readhesions to the puboischial rami the penis was buried in a scrotal tunnel. Six months later the denuded shaft was resurfaced with one split thickness skin graft and a zigzag seam on the ventral side was made. The patient voids with good stream, has spontaneous erections and nocturnal emissions. During 10-years follow-up after the reconstruction two complications, namely a stricture of the urethra and a slight dorsal tethering of the penis caused by a scarred pubic skin were treated. The problems of the a reconstruction type and resurfacing of the penis in childhood are discussed. PMID- 1308315 TI - Detecting cardiac valvular pathology in patients with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is associated with multiple cardiac complications, including valvular damage and an increased risk of bacterial endocarditis. The purpose of this study was to evaluate prospectively a group of patients with SLE for the presence of valvular abnormalities in order to assess their candidacy for antibiotic prophylaxis prior to invasive dental procedures. Of the 43 participants, 19 (44%) had echocardiographic evidence of valvular pathology; however, only seven (16%) had a physical exam consistent with pathologic valve anatomy or function. Because of the high percentage of SLE patients with valvular abnormalities, and the poor sensitivity of the physical exam, referral to a cardiologist for echocardiography is suggested prior to invasive dental care for patients with SLE. If cardiac valvular pathology is detected, antibiotic prophylaxis should be considered. PMID- 1308316 TI - An educational "treatment plan" model for the general practice residency. AB - The need to match residency program experiences with the interests, skills, and personal goals of residents is influenced by many factors. A structured system, the Individualized Educational Plan, is described which provides a formalized means of addressing each of these needs. The development of an educational plan, similar in concept to the development of a formal treatment plan for patients, provides the basis for the system. The system provides both the program director and the resident with the means to evaluate in detail the resident's progress and the program's performance in helping the resident achieve competency. PMID- 1308317 TI - Informed consent and the geriatric dental patient. AB - Dental professionals are increasingly aware of their ethical responsibility to permit patients to participate in treatment decisions through the informed consent process. At the same time, growing numbers of geriatric patients present special challenges that can jeopardize the use of informed consent. Consequently, the use of informed consent with geriatric patients warrants special analysis due to complicating factors such as patient passivity and questionable competency. This article establishes the relationship between the ethical principle of autonomy and informed consent while examining factors that must be present in order for a valid informed consent to be obtained. Additionally, the article addresses informed consent issues regarding competent patients, geriatric patients with fluctuating or uncertain competency, and patients who are clearly incompetent. PMID- 1308318 TI - Pica: a peculiar behavior with oral involvement. AB - Pica is a behavior commonly displayed by children, pregnant females, and individuals with mental retardation. A population of institutionalized adults with mental retardation was assessed for pica. Of this population, 10.8% were identified with this behavior. Also, this article discusses aspects of pica and describes how this behavior can affect the mouth. PMID- 1308319 TI - Prosthetic rehabilitation of the oral cancer patient: a clinical report. PMID- 1308320 TI - Treatment outcomes for specific subtypes of dental fear: preliminary clinical findings. AB - In order to examine the clinical treatment outcome for dental fears, we examined 111 active patient records retrospectively using an 80-item structured format. Subjects were from three fear subtypes: needle phobic (N = 15), gagger (N = 11), and non-specific dental fear (N = 85). Mean subtype Dental Fear Survey scores ranged from 72.3 to 81.0. Patients received either behavioral therapy alone (N = 85) or behavioral therapy with a nitrous oxide or IV sedation adjunct (N = 26). Mean psychological treatment time was 3.9 hours (SD = 2.8 h) and did not differ by fear subtype (p > 0.05). All patients successfully completed initial dental treatment. Relapse of fear requiring additional psychological treatment occurred only in the non-specific fear subtype (rate = 11.2%). Patients receiving pharmacologic adjuncts to behavior therapy (nitrous oxide) experienced less relapse. PMID- 1308321 TI - Technique for construction of dental molds for high-dose-rate remote brachytherapy. AB - High-dose-rate remote (HDR) brachytherapy eliminates radiation exposure hazard to personnel, allows for optimum dosage planning (dosimetry), and delivers high radiation dose close to the tumor in only a few minutes. The catheters can be incorporated into a fixed geometry within a mold, allowing for repeated treatments without the need for repeated implantation of radioactive isotopes or repeated dosimetry. This article presents the use of HDR brachytherapy in three patients to illustrate the advantages of HDR brachytherapy for the treatment of head and neck cancers in the following circumstances: (a) for outpatient therapy, (b) as an addition to or potentiation of external beam irradiation, (c) for preservation of function of regional structures, (d) for optimization of dosimetry, and (e) for palliation. It requires close interaction among the radiation oncologist, head and neck surgeon, and the dental oncologist and/or maxillofacial prosthodontist in order for optimum benefit for the patient to be achieved. PMID- 1308322 TI - Are dental practices less productive with older patients? Comparison of alternative output measures. AB - This study assessed the effects of increased visits by older dental patients on alternative measures of time- and dollar-based practice productivity. The Minnesota Dental Practice Analysis System was used for analysis of data from 31 practices (12,818 patients visits) reporting increased visits by older adults between June, 1980, and December, 1984. Results suggested that the productivity effects associated with older patient visits were highly dependent on the practice output measure selected. While increased visits by patients aged 70 and over were associated with increased monetary productivity per patient visit, time and monetary productivity per practice day were found to decline. An association between increased proportions of older patients visits and increased dentist minutes per visit appeared to account for this. This econometric analysis tends to support the notion that dental practices are less productive with older patients. PMID- 1308324 TI - Modified orthodontic treatment goals in a patient with multiple complicating factors. AB - This paper reviews orthodontic care in patients who are in nontraditional categories. Specific orthodontic management of a patient who had severe hemophilia, seropositivity for anti-HIV Ab, and Hepatitis B surface antigen is reviewed. The importance of defining acceptable treatment goals in these patients is of paramount importance. PMID- 1308323 TI - An in vitro analysis of a sustained release system for the treatment of denture stomatitis. AB - This study investigated the feasibility of a sustained-release delivery system for the treatment of denture stomatitis using four antifungal agents (chlorhexidine, clotrimazole, fluconazole, and nystatin) incorporated into a tissue conditioner (Lynal) at zero (control), low, medium, and high concentrations. Hardness of all experimental groups increased with both concentration and time, but remained within the range of clinical acceptability (Shore A < or = 49). Mean tensile strength increased in all experimental groups and was significantly stronger than the control for at least one concentration level of each drug, p < or = 0.05. All failures for tensile-strength testing were characterized as cohesive. All drugs demonstrated release from the tissue conditioner matrix and inhibition of growth of C. albicans that was either total, dose-related, or related to incubation time prior to inoculation. All controls supported growth. PMID- 1308325 TI - A chemomechanical system for caries removal and glass ionomer cement to restore fixed partial denture abutments. AB - When a fixed partial denture fails due to recurrent caries under the casting of the abutments, a remake process usually requires a great deal of cooperation, multiple lengthy appointments, and financial resources. Many patients with special needs may not have the cooperation, tolerance, and resources to support such treatment. This paper describes an alternative method that utilizes a chemomechanical system for caries removal followed by a conventional restorative material to treat those patients. PMID- 1308326 TI - Family member and guardian acceptance of dental services for nursing home residents. AB - The decision to utilize dental treatment often rests with a nursing home resident's family member or guardian, and factors associated with family member/guardian acceptance of dental services for residents have not been identified. This paper reports the results of a study which found that nearly 66% of nursing home residents' next of kin identified themselves as being primarily responsible for making health care decisions for the residents. Among these 109 resident/next of kin pairs, utilization of dental services by the residents was associated with younger next of kin, next of kin with higher levels of education, and next of kin who perceived dental need for the resident. In addition, residents who were female, physically mobile, not mentally alert, dentate, and had fewer years of education had dental services accepted for them at a higher rate than did residents who were male, physically immobile, alert, edentulous, or had more years of education. Findings suggest that more effort should be directed at educating the next of kin of nursing home residents in the value of dental care among the elderly. PMID- 1308327 TI - The "new" ADA: The Americans with Disabilities Act. PMID- 1308328 TI - Medical histories and records keeping in Fort Worth dental practices. PMID- 1308329 TI - The reality of dental CAD-CAM: hype or hope? AB - Dental CAD-CAM has become a clinical reality. It holds great promise to help provide a higher level of service to the patient, while allowing the dentist to spend more time on patient needs than on the mechanics of restoration production. Still, this technology is not suited for every dental office. This paper discusses the technique of CAD-CAM, its potential and its limitations so the dentist can better evaluate the appropriateness of this new modality for his or her own office. PMID- 1308330 TI - Should Medicare providers be Peace Corps volunteers? PMID- 1308331 TI - What is the ADA doing to help female and ethnic dentists? PMID- 1308332 TI - Personality patterns of Texas dentists: a study using the bi/polar theory. AB - Are individuals with certain personality styles uniquely attracted to dentistry? A recent study with 218 Texas dentists using the Bi/Polar Inventory of Core Strengths showed that the dentists were more thinking (57.3%) than risking, profoundly more practical (78.0%) than theoretical, and more independent (67.9%) than dependent. Compared with the general population, dentists were significantly more thinking, practical and independent. Of the eight personality styles, Pattern II (thinking-practical-independent) (29.4%) was the only pattern significantly over-represented among the dentists compared with the general population. However, Pattern I (thinking-practical-dependent) (17.4%) was also over-represented at the trend level. Significantly under-represented among the dentists were Pattern V (risking-practical-dependent) (6.9%) and Pattern VI (risking-theoretical-dependent) (3.2%). Results suggest at least some personality influence on attraction to dentistry. PMID- 1308333 TI - Grateful Med/Loansome Doc: electronic resources for every dentist. PMID- 1308334 TI - Radiation protection & regulations. PMID- 1308335 TI - ADA and AAP introduce dentists to new time saving periodontal evaluation system. PMID- 1308336 TI - Common malignancies of the oral cavity. PMID- 1308337 TI - Development of the principle of guided tissue regeneration. AB - Guided tissue regeneration (GTR) is a new treatment principle in surgical therapy, developed from the result of studies in experimental animals. It implies that only those types of cells with the capacity of producing regeneration are allowed to invade the surgically treated lesion during healing. This is accomplished by the placement of a physical barrier with excludes undesirable types of tissue. Healing of periodontal bony lesions can be obtained predictably by treatment according to the principle of guided tissue regeneration but several studies have suggested that the same principle can also be applied successfully in other fields of dentistry. In implantology, the method has been used for immediate placement of implants into extraction sockets, for healing of peri implant bony defects and for augmentation of atrophic alveolar ridges. PMID- 1308338 TI - Guided tissue regeneration and GTAM for periodontal regenerative therapy, ridge augmentation and dental implantology. AB - In dentistry, the goals of regenerative therapy are to gain new attachment around natural teeth, improve the aesthetics and ridge form in cases of collapsed or deformed ridges and increase the amount of available bone for osseointegrated implants. The purpose of this paper is to describe the dental and periodontal applications of the principles of guided tissue regeneration (GTR) and guided tissue augmentation material (GTAM) therapy. Successful results can be achieved around periodontally diseased natural teeth, however, the procedures are not fully predictable at this time. Correct membrane placement and proper choice of defect configuration in the use of GTR can enhance clinical attempts to gain new attachment. Regenerative therapy can be utilized to augment edentulous ridges and improve ridge-pontic relationships as well as improve aesthetics in ridge abnormalities. Edentulous ridges augmented by GTR can have increased amount of bone height and width for endosseous implant placement. In areas where non-mobile implant fixtures have lost some osseous support, GTR has demonstrated successful gain of new bone support. PMID- 1308339 TI - Implant prosthodontics--an adjunct in periodontal prosthesis. Part I and II. Diagnosis, treatment planning, and sequencing of therapy. AB - Periodontal prosthesis can be defined as "those restorative and prosthetic endeavors that are absolutely essential in the treatment of advanced periodontal disease". The sequence of therapy is planned so that the basic contributing factors of inflammation and trauma from occlusion are brought under control. Experimental and clinical research over the last decade has shifted the focus of periodontics towards increased use of guided tissue membrane techniques. Today, as a result of the longitudinal studies on the viability of endosseous implantology, implants used as an integral part of Periodontal Prosthesis now offer the patient and dentist a more stable and predictable restoration. These articles focus on the comprehensive treatment of the partially edentulous situation. The first two parts address diagnosis, treatment planning and treatment sequencing in the overall management of the compromised dentition. PMID- 1308340 TI - Implant prosthodontics-an adjunct in periodontal prosthesis. Part II. Treatment planning and sequencing of therapy. PMID- 1308341 TI - Biocompatibility and biofunctionality of implanted materials. AB - The mechanical and chemical properties of metals, such as titanium, titanium based alloys and cobalt-based alloys, and ceramics, such as Bioglass and calcium phosphate, make them suitable for implant applications. However, several factors affect the biologic response to these implanted materials. The predominant tissue found at the implant interface is affected by implant stability, material biocompatibility, and implant design and implant placement into the surgical site. Improvements in implant design and surface preparation may improve implant longevity and fixation for all implants materials. PMID- 1308342 TI - Monitoring the periodontal microbiota as an adjunct to periodontal therapy: rationale, interpretation of test results and application to patient management. AB - Recent developments in our understanding of the relationship of the oral microbiota to periodontal diseases have led to improved approaches to controlling the pathogenic influence of certain bacterial species. In addition to non specific control of bacterial accumulations in the sulcus region, antibiotics may be useful in suppressing persistent species with pathogenic potential. This approach is indicated in cases that do not respond adequately to mechanical plaque control measures or certain categories of periodontal diseases likely to be caused by a specific infection. Monitoring the composition of the microbiota before, during and after antimicrobial therapy is helpful in the selection of appropriate antimicrobial agents, monitoring the effectiveness of the therapy and detecting the return of undesirable microorganisms. PMID- 1308343 TI - Physiology of osseous and fibrous integration. AB - The adaptation of bone to dental implants by rigid osseous integration is believed by many to be the hallmark of clinical success. However, many implants that are slightly mobile with a fibrous interface also function well in clinical application. Physiologically, why does bone respond by rigidly integrating one implant and producing a fibrous interface with another? The healing mechanism for rigid osseous integration is well known and accepted. Conversely, the development of a fibrous interface is incompletely understood. This article suggests a unified concept of the interrelationship between fibrous and osseous integration. PMID- 1308344 TI - The biology and morphology of the implant-tissue interface. AB - The replacement of teeth in fully partially edentulous patients with dental implants has become an acceptable standard of care. The improved efficacy and success of dental implants has been the result of rigid adherence to the prerequisites for osseointegration. This direct bone-to-implant contact has been described histologically and the success or failure of dental implants may depend upon the relative percentage of this contact. Connective tissue and epithelial interactions with implant surfaces have also been characterized, however, to a lesser degree. Connective tissue morphology was shown to be dependent upon the type of implant surface, i.e. smooth versus porous. The epithelial interactions with implants seems to be similar to those around teeth. The formation of a peri implant sulcus lined coronally with a sulcular epithelium and more apically with a junctional epithelium has been demonstrated. A better understanding of the interactions between the implant surfaces and the surrounding tissues may enhance treatment results. PMID- 1308345 TI - GMS syndrome: a new dominant condition with goniodysgenesis, mental retardation, and short stature. AB - We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature. The pattern of occurrence is compatible with either autosomal dominant or X-linked inheritance. PMID- 1308346 TI - Cleft lip (+/- cleft palate) etiology: a search for solutions. PMID- 1308347 TI - Rett syndrome: a search for gene sources. AB - A series of 77 Swedish females with classical Rett syndrome were genealogically traced as far back as possible, in most cases to 1720-1750, or 7-10 generations. Details were collected concerning approximately 8,000 ancestors. Common ancestry was seen in 2 pairs of females with Rett syndrome. Thirty-nine of the 77 Rett females were traced to 9 small and separate rural areas, and 17 pairs even came from the same farm or homestead. The common origin was found equally often among descendants of the father as of the mother. In 9 cases, the father came from one and the mother from another of the 9 specific "Rett areas." These observations, combined with the finding of a raised rate of consanguineous marriages in the paternal as well as in the maternal ancestry, point to a genetic transmission. Analyses of parental ages at birth and of birth order gave normal results. PMID- 1308348 TI - Deletion of chromosome 15pter-->q11.2 due to t(Y;15) in a boy with Prader-Willi syndrome. AB - Chromosome analysis of lymphocytes from a patient with the clinical presentation of Prader-Willi syndrome showed the presence of 45 chromosomes, including a der(Y) resulting from an unbalanced t(Y;15)(q12;q11.2). In situ hybridization using DYZ3 and DYZ2 showed positive signals at the paracentromeric region on the short arm and at the heterochromatic region of the long arm of the Y chromosome, respectively. The Prader-Willi syndrome in this patient is caused by the deficiency of a very small region involving 15cen-->q11.2. PMID- 1308349 TI - Kenny-Caffey syndrome in two sibs born to consanguineous parents: evidence for an autosomal recessive variant. AB - We report on 2 sibs with manifestations of the Kenny-Caffey syndrome born to normal, consanguineous parents. Clinical manifestations included dwarfism, internal cortical thickening and medullary stenosis of tubular bones, poorly ossified skull bones, and hypocalcemia. The younger of the two died during a tonic convulsion. The older had neonatal hypoparathyroidism and is now a short intelligent, 1-year-old child. This family gives new support to the existence of an autosomal recessive variant of the syndrome. PMID- 1308350 TI - Phenotypically dissimilar hypophosphatasia in two sibships. AB - Autosomal dominant and autosomal recessive forms of hypophosphatasia have been reported; generally the clinical picture runs true to form in families. In each of 2 kindreds, 2 sibs were clinically affected by hypophosphatasia to a markedly different extent. One set of sibs showed the lethal (perinatal) and infantile forms. The other showed the dental and adult forms. In both families there was consanguinity, albeit distant, and clinical expression in sibs supporting autosomal recessive inheritance. PMID- 1308351 TI - Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings. AB - We present male monozygotic twins with thanatophoric dysplasia (TD) type I concordant for long bone abnormalities and discordant for cloverleaf skull. The twins were the product of the second pregnancy of unrelated parents, with advanced paternal age. Prenatal diagnosis and postmortem examination showed severe rhizomelic shortness of limbs, bowing of the long bones with "telephone receiver" femora in both twins, and cloverleaf skull and hydrocephalus in one of them. It is now accepted that most of cases of TD, such as in the present report, represent an autosomal dominant mutation with a high new mutations rate. PMID- 1308352 TI - Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes. AB - Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus. PMID- 1308353 TI - Waardenburg syndrome associated with meningomyelocele. PMID- 1308354 TI - 9qh+ variant band in two families. PMID- 1308355 TI - Holoprosencephaly and maternal low-calorie weight-reducing diet. PMID- 1308356 TI - Arthrogryposis multiplex congenita with renal and hepatic abnormalities. PMID- 1308357 TI - Late-onset psychosis in the velo-cardio-facial syndrome. PMID- 1308358 TI - Radiculomegaly of canine teeth and congenital cataracts: confirmation of a syndrome. PMID- 1308359 TI - Deletion of the proximal short arm of chromosome 8. AB - We report on a 5-month-old boy with a de novo interstitial deletion of the proximal short arm of chromosome 8 (p21p11.2). He manifested bilateral cleft lip and palate, and apparent hypogonadism. Four previous case reports with similar deletions (p11.1p21) were associated with hypogonadotropic hypogonadism [Beighle et al., Hum Genet 38:113-121, 1977] and hereditary spherocytosis (HS) [Chilcote et al., Blood 6:156-159, 1987; Kitatani et al., Hum Genet 78:94-95, 1988; Lux et al., Nature 345:736-739, 1990]. Our patient has no demonstrable red blood cell abnormality, suggesting that the gene for HS is located in the region 8p11.1 to 8p11.2. PMID- 1308360 TI - Ectopia lentis and aortic root dilatation in congenital contractural arachnodactyly. AB - Congenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis, and a distinct "crumpled ear" deformity. While the disorder is similar to Marfan syndrome, it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echocardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients. PMID- 1308361 TI - Stable ring chromosome 21: molecular and clinical definition of the lesion. AB - Ring chromosome 21 results in deletions of chromosome 21. We report on a cytogenetic and molecular analysis of a 4-generation family segregating a stable ring chromosome 21 in 4 relatives. To investigate the molecular structure of the ring chromosome, we have analyzed the DNAs of the transmitted ring in a mother and her daughter. The daughter presented at the age of 2 years with severe growth retardation and microcephaly, whereas her mother had microcephaly but normal intelligence. High resolution chromosome analysis of both cases showed the ring chromosome to be r(21)(p13q22) resulting in deletions of 21p and 21q22. The molecular content of the ring chromosome was determined using quantitative Southern blot analyses of 5 random DNA sequences and 4 expressed genes assigned to chromosome 21 and mapping in the region of q22.3. We have shown that collagen type VI, alpha 2 (COL6A2,) S100 protein, beta polypeptide (neural), (S100B), and D21S44 are present in only one copy in both ring carriers, while CRYA1, CBS, D21S43, D21S42, D21S41, and D21S39 are present in two copies. These data and the breakpoints defining the deletion in these patients show that deletion of COL6A2 and S100B is compatible with normal function and confirm the physical map of 21q22.3 by placing COL6A2, S100B, and D21S44 in very distal 21q22.3. Patients with such small deletions provide unique models for understanding the biological and clinical significance of aneuploidy for specific expressed genes. PMID- 1308363 TI - Alagille syndrome with de novo del(20) (p11.2). AB - We report on an Arab boy with Alagille syndrome and a de novo deletion of the short arm of chromosome 20 with a 46,XY, del(20)(p11.2) chromosome constitution. Other reported cases are briefly reviewed. PMID- 1308362 TI - De Barsy syndrome: report of a case, literature review, and elastin gene expression studies of the skin. AB - Several "progeroid" syndromes have now been identified. The De Barsy syndrome is an autosomal recessive syndrome of dwarfism, mental deficiency, an "aged" appearance at birth, abnormal elastic fibers on skin biopsy, and lax skin, large helices, eye abnormalities, lax joints, hypotonia, and athetoid posturing. We report one case and review 11 cases from the literature. To understand the abnormal appearance of the elastic fibers on biopsy, we performed elastin gene expression studies on fibroblasts cultured from our patient's skin. Molecular hybridization studies revealed reduced elastin mRNA steady-state levels as compared with age matched control individuals. Assuming normal rates of mRNA translation, reduced elastin synthesis would occur. Diminished dermal elastin content could explain the altered cutaneous elasticity, decreased elastic fibers in the skin, and many clinical manifestations of individuals with this condition. PMID- 1308364 TI - Congenital hypothalamic hamartoma syndrome: nosological discussion and minimum diagnostic criteria of a possibly familial form. AB - We report on congenital hypothalamic hamartomas, discovered at autopsy in 3 unrelated fetuses. In the first 2 patients, the tumor was associated with skeletal dysplasia only. In the third patient, it was part of a non-random congenital malformation association, suggestive of Meckel syndrome. In one family, a previous boy died soon after birth with similar craniofacial and skeletal abnormalities. As far as we know, the association between isolated skeletal dysplasia and congenital hypothalamic hamartomas has not yet been documented in the literature. Nevertheless, a spectrum of skeletal abnormalities has been described in association with congenital hypothalamic "hamartoblastoma" and a constellation of variable visceral malformations under the eponym of "Pallister-Hall syndrome" (PHS). A detailed analysis of the PHS reported cases shows that only skeletal dysplasia and oro-facial abnormalities are present constantly. They show similarities with those found in our first 2 cases. These findings prompt us to consider skeletal dysplasia and oro-facial abnormalities as common denominator and minimum criteria required to define a nosologically distinct, possibly familial entity, which we suggest calling "congenital hypothalamic hamartoma syndrome" (CHHS). PMID- 1308365 TI - Genetic analysis of cleft lip with or without cleft palate in Madras, India. AB - We performed a genetic analysis of 331 non-syndromic cleft lip with or without cleft palate (CL +/- P) proband families ascertained in Madras, India. Predictions of the multifactorial threshold (MF/T) model are tested; goodness-of fit tests of the MF/T model and complex segregation analysis are also utilized to clarify the genetic etiology of CL +/- P in this study population. There was little evidence for the MF/T model. The most reasonable conclusion from mixed model analysis is that of a major locus with reduced transmission probability. This is not altogether surprising if manifestation of CL +/- P also depends on in utero exposure to harmful environmental agents during the critical period of facial development, as suggested by Melnick et al. [1980] and demonstrated in an animal model of CL +/- P [Melnick et al., 1981]. Further the results in the Madras population are quite similar to those in other populations of Europe and Asia. PMID- 1308366 TI - Autosomal dominant inheritance of tetramelic monodactyly. AB - We report on tetramelic monodactyly with autosomal dominant inheritance. The propositus and all affected relatives had only digital malformations as determined by physical examination or history. Since it could not be determined that the involved digits of the propositus or relatives were fifth fingers and toes, we conclude this to be the first report of this type of hand and foot malformation with autosomal dominant inheritance. PMID- 1308367 TI - Head circumference of children with Down syndrome (0-36 months) AB - This study provides statistically appropriate head circumference reference curves for males and females with Down syndrome (DS) from birth to 36 months of age. A total of 239 males and 182 females from five study populations, yielding a combination of cross-sectional and longitudinal data, were used for the analysis. The method of least squares was used to test the fit of the growth model y = a+bx+c[log(x + 1)], where x is age in months. These standardized curves should provide information of value in the medical, physical, and developmental management of children with DS. PMID- 1308368 TI - Cockayne syndrome: review of 140 cases. AB - To define diagnostic criteria for Cockayne Syndrome (CS) and to identify in detail the complications of the condition, a comprehensive review of 140 cases of CS was performed. Criteria required for the diagnosis include poor growth and neurologic abnormality; other very common manifestations include sensorineural hearing loss, cataracts, pigmentary retinopathy, cutaneous photosensitivity, and dental caries. The mean age of death in reported cases is 12 3/12 years, though a few affected individuals have lived into their late teens and twenties. Prenatal growth failure, congenital structural eye anomalies, severe neurologic dysfunction from birth, and the presence of cataracts within the first 3 years of life are predictors of severe disease and early death. In contrast with other disorders of chromosome or DNA repair, cancer has never been reported in a classical CS patient, and there appears to be no predisposition to infectious complications. The wide spectrum of symptoms and severity of the disease suggest that biochemical and genetic heterogeneity exist. CS is an uncommon but devastating genetic condition which will be better understood as the biochemical interrelationships between DNA replication and repair, and between growth, homeostasis, and oncogenesis are unraveled. PMID- 1308369 TI - Tracheal agenesis with diaphragmatic hernia. AB - A case is presented of a newborn infant with Type III tracheal agenesis and a right diaphragmatic hernia which represents the first report of this occurrence. Associated multi-organ anomalies and possible embryologic relationships are discussed. PMID- 1308370 TI - Progressive bilateral nasal alar collapse: a dominantly inherited trait. AB - We describe a 47-year-old woman with progressive bilateral collapse of the alae nasi first noted at age 16 years. Her dizygotic twin daughters have similar nasal collapse beginning at age 20 years. This condition appears to be inherited as a dominant trait. Although plastic surgical correction has been successful for a phenotypically similar condition due to trauma, surgical correction must be considered cautiously in individuals with an atraumative, possibly inherited, progressive form of the disorder. PMID- 1308371 TI - Pentalogy of Cantrell and associated midline anomalies: a possible ventral midline developmental field. AB - Five cases of the Pentalogy of Cantrell (PC), ascertained through the Baltimore Washington population-based study of infants with congenital cardiovascular malformations, represent a regional prevalence of 5.5/1 million liveborn infants for this disorder. Three of these patients had cleft lip with or without palate. Review of the reported literature of the Pentalogy of Cantrell and various combinations of the anomalies within the spectrum of this pentad suggests that the PC defines a specific midline ventral developmental field. Cleft lip with or without cleft palate and encephalocele tend to specifically associate with ventral midline anomalies within the spectrum of PC. These associations might either illustrate the previously observed tendency of specific occurrence of certain combinations of midline defects or represent defined subunits of the midline developmental field. PMID- 1308372 TI - Agonadism in a 46,XY patient with CHARGE association. AB - We report on an infant girl born with findings of CHARGE association who proved to be a genetic male (46,XY) on cytogenetic study. Further investigation of the genitalia demonstrated partially female internal organs but absence of gonads by ultrasonography, hormone studies, and absence of ZFY by DNA probe of Yp. Pelvic exploration confirmed lack of gonadal tissue and uterus. Facial phenotype was compatible with CHARGE appearance. PMID- 1308373 TI - Long-acting local anesthetics in dentistry. AB - Long-acting local anesthetics have proved to be effective for the suppression of both intraoperative and postoperative pain. They are useful for lengthy dental treatments and for prevention of severe pain following many types of surgical procedures. Although the currently available long-acting local anesthetics for dentistry have minimal side effects in the doses usually employed, there are potential problems. Bupivacaine, for example, can cause significant cardiac depressant and dysrhythmogenic responses. Etidocaine has less pronounced effects on the cardiovascular system, but its use may be associated with inadequate control of intraoperative bleeding. A new long-acting local anesthetic, ropivacaine, appears to offer advantages over either of the currently used long acting agents. PMID- 1308375 TI - Serum potassium after enflurane-succinylcholine induction of anesthesia in children receiving rectal midazolam as premedication. AB - The administration of succinylcholine causes an increase in serum potassium (K+) concentrations in healthy patients. The purpose of this study was to investigate serum K+ changes following intravenous succinylcholine in children and to evaluate the effect of rectal midazolam pretreatment on these changes. Forty healthy children between the ages of 2 and 7 yr, and who were to undergo oral surgical procedures under general anesthesia were randomly assigned to receive either placebo (saline) or 0.25, 0.35, or 0.45 mg/kg midazolam administered rectally as premedication 30 min before induction of inhalational anesthesia. Blood was drawn after induction with enflurane and at 1, 2, 3, 4, and 5 min after administration of 1 mg/kg succinylcholine to determine changes in serum K+. Although the results indicate a significant increase in serum K+ after succinylcholine in all groups, midazolam pretreatment failed to cause any observable attenuation in the hyperkalemic response. PMID- 1308374 TI - Ketamine: a review of its pharmacologic properties and use in ambulatory anesthesia. AB - The administration of intravenous agents is the most commonly used method in Canada and the United States to produce sedation or general anesthesia for dental procedures. Ketamine, a dissociative anesthetic, has several advantageous physical, pharmacokinetic, and pharmacodynamic properties. It can be used to induce anesthesia, sedation, analgesia, and amnesia. Ketamine can maintain functional residual capacity, induce bronchodilation, and avoid cardiovascular depression. However, adverse effects have been demonstrated, such as cardiovascular stimulation and unpleasant emergence phenomena, both of which may be modulated by supplementation with benzodiazepines. An increase in the use of ketamine for ambulatory anesthesia has recently been advocated. This review of the literature supports the use of ketamine as an effective agent for selected anesthetic procedures. PMID- 1308376 TI - Responses to intravenous sedation by elderly patients at the Hokkaido University Dental Hospital. AB - Geriatric patients who undergo intravenous sedation require careful intraoperative management, because respiratory and circulatory depression usually accompanies the administration of recommended adult sedative doses. This study examined results when a single benzodiazepine, diazepam or flunitrazepam, was carefully titrated to a clinical endpoint of conscious sedation. A total of 335 cases was divided into seven age groups. Mean sedative doses gradually decreased with age. The 60- to 69-yr group required about 75% of the adult recommended dose, the 70- to 79-yr group required 40% to 60%, and the 80- to 89-yr group required 30% to 45%. Pulse oximetry values also declined with age; respiratory depression was observed mainly in elderly patients. Declines in blood pressure after benzodiazepine administration were not correlated with age. The rise in blood pressure normally observed intraoperatively was suppressed both in young as well as old patients. We conclude that intravenous conscious sedation in elderly patients reduces stress-induced cardiovascular stimulation and that respiratory depression may occur at even low sedative doses. PMID- 1308377 TI - Anesthetic effect of EMLA occluded with Orahesive oral bandages on oral mucosa. A placebo-controlled study. AB - The efficiency of a topical anesthetic occluded with Orahesive Oral Bandage was investigated. Experimental pain was provoked by needle insertions into two palatal test areas in 20 healthy subjects. Pain, estimated on a 100-mm visual analogue scale (VAS), decreased significantly from 23.5 mm to 10.5 mm at the greater palatine foramen and from 51.5 mm to 35.0 mm at the incisive foramen after application of a eutectic mixture of local anesthetics (EMLA). No significant change in pain perception was obtained after placebo application. The EMLA cream and the Orahesive Oral Bandages were well accepted by the subjects, as only two out of 20 subjects experienced slight gagging reflexes and only three considered the taste unpleasant. No other adverse reactions were observed. Occlusion of topical anesthetics seems to be a useful technique for achieving superficial mucosal anesthesia. PMID- 1308378 TI - Comparison of propofol infusion and isoflurane for maintenance of anesthesia for dentistry in mentally retarded patients. AB - A continuous infusion of propofol following an induction dose of 2 mg/kg was compared with thiopental/isoflurane for the induction and maintenance of anesthesia in 20 mentally retarded outpatients undergoing routine dental procedures. The infusion rate of propofol and the concentration of isoflurane were adjusted to maintain the heart rate and blood pressure within +/- 25% of the baseline values. Postoperative wakefulness was assessed using a 100-mm visual analogue scale at the time of extubation and at 5, 10, 15, 30, 60, 90, and 120 min after extubation. Both agents provided adequate anesthesia for the treatment, and no major adverse reactions occurred. Recovery was more complete during the first hour after extubation in the propofol group, and these patients were discharged earlier. PMID- 1308379 TI - Adverse reactions associated with norepinephrine in dental local anesthesia. AB - Two cases are presented in which a 40-yr-old woman and a 20-yr-old woman developed severe headaches after injection of the local anesthetic Xylestesin-F (3% lidocaine with 1:25,000 norepinephrine). It is suggested that these severe headaches may have been associated with acute transient hypertensive episodes following injection of the local anesthetic. A review of the literature indicates that norepinephrine, at least at a concentration of 1:25,000, should be avoided because of its potential for cardiovascular disturbances. PMID- 1308380 TI - [Critical re-evaluation of the usefulness of evoked potentials in clinical neurology]. PMID- 1308382 TI - [Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of cerebral infarction]. AB - In non-diabetic patients, the appearance of hyperglycemia in the acute phase of stroke is related to the extension of cellular injury, and hence to the physiologic stress response. In animal models of ischemic insult, the deleterious effects of hyperglycemia depend heavily on the production of lactic acid "via" activation of the glycolytic anaerobic pathway. The abnormal production of lactic acid and consequent tissular acidosis appear mainly in the early post-reperfusion period, or in states of marked but partial reduction of blood flow. A direct reduction of cerebral blood flow and, perhaps, the production of a hyperosmolar state may contribute to worsening of the ischemic injury. In diabetic patients, previous hemorrheologic and microcirculatory changes, and a greater susceptibility to infections may additionally reduce the chances of complete recovery after stroke. PMID- 1308381 TI - [Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of cerebral infarction]. AB - We accessed the potential impact of diabetes mellitus and hyperglycemia on early prognosis in a study of 109 cases of CT proved brain infarction. Main end-points of this study were 30-days case-fatality rates and the probability of early discharge or prolonged hospitalization. Proportions of patients exhibiting diverse evolutions were compared by Fisher's test and, when the number of observations permitted, by chi-square test. Diabetes mellitus was diagnosed by history in 15.6% (17 patients). In 86 cases analysed within 72 hours of admission, hyperglycemia (glucose level higher than 110 mg/dL) was detected in 67.4% (including all 14 diabetic patients (35.3% vs 21.7%; p = 0.18), but these patients probably were discharged early less frequently (23.5% vs 51.1%; p = 0.06). Compared to the normoglycemic patients, hyperglycemic patients also fared worse, when considering altogether the early discharge and case fatality rates and the need for prolonged hospitalization (p = 0.06). They also exhibited a nonsignificant increase in early case fatality rate (31% vs 15.4%; p = 0.21) and a markedly reduced chance of obtaining early hospital discharge (37.9% vs 65.4%; p = 0.03). Case fatality rates were maximal in diabetic hyperglycemic patients (42.9%) and seemed intermediate in non-diabetic hyperglycemic patients (27.3%). Considering the three end-points evaluated, the apparent differences between non diabetic hyper and normoglycemic patients did not reach statistical significance (p = 0.19). These results suggest that both diabetes mellitus and hyperglycemia "per se" have deleterious effects on the clinical evolution of patients with cerebral infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308383 TI - Follow-up study of macrocephalic children with enlargement of the subarachnoid space. AB - Eighteen macrocephalic children with enlargement of the subarachnoid space (ESAS), with or without mild ventricular dilatation, were followed prospectively to a mean age of 56 months. All were born at term, with uneventful neonatal period and negative tests for congenital infections. There were 17 boys and 1 girl and the mean follow-up period was 46 months (8-58 months). The initial neurologic evaluation, between ages of 2 to 33 months, disclosed abnormalities in 2 cases. At the follow-up one was still abnormal and the other had a normal neurological examination. Another child, who had a normal neurological examination at the age of 5 months, at the age of 7 years and 7 months had an IQ of 77. Thus the abnormality rate at follow-up was 11%. The OFC returned to the normal range in 45% of the children at the follow-up period. There were no cases of intracranial hypertension. One infant had subdural taps performed at the age of 13 months that disclosed a fluid with the same characteristics as the CSF. All the children had a CT-scan performed at the beginning of the study that revealed a large subarachnoid space; in 77% it was associated with mild ventricular dilatation. Eleven had CT-scans repeated, during the study period, which showed resolution of the process in 3 cases, improvement in 2, and unchanged in 6. We conclude that enlargement of the subarachnoid space in macrocephalic children is often a benign entity. ESAS and macrocephaly will still be present in the majority of children in the long-term follow-up. PMID- 1308384 TI - [Intermittent prophylaxis in febrile convulsions with oral diazepam]. AB - Intermittent prophylaxis with oral diazepam is presented as an optional treatment for febrile seizures. This proposition is justified by the severe side effects of the currently used chronic anticonvulsant drug therapy in febrile seizures (phenobarbital and valproate). Nineteen patients aged between 3 months and 5 years were treated. They had either simple or complex febrile seizures. Sixteen patients had at least one prognostic factor for recurrence of febrile seizures: first febrile seizure before 15 months of age, positive family history for epilepsy or febrile seizures, occurrence of a complex febrile seizure or abnormal neurological examination. Three patients had none (cases 8, 12 and 13). We recommended 2.5mg b.i.d. for children younger than 12 months, 5mg b.i.d. for children older than 12 months and younger than 3 years, and 7.5 b.i.d. for children older than 3 years. The results showed that only one patient had febrile convulsions while taking adequate diazepam dosage. Transient side effects occurred in 36.8% of the cases. PMID- 1308385 TI - [Electroneurography of the facial nerve: methods of stimulation and records]. AB - In this study it is, intended to establish the more appropriate points to register the compound action potential from m. frontalis m. orbicularis oculi and nasolabial fold muscles. The optimum site for stimulating electrodes and differences between the first and the last compound action potentials after 20 consecutive stimuli delivered at 1 Hz were analysed. PMID- 1308386 TI - [Cytopathologic diagnosis of neuroepithelial tumors by the smear technique]. AB - We studied 198 cases of neuroepithelial tumours with intra-operative diagnosis made by smears comparing the accuracy rates with the final paraffin section diagnosis. In 90.6% of cases the final diagnosis obtained on paraffin preparations was similar to that made on smears. In the group of cases with cytological diagnosis not confirmed by paraffin sections the majority of cases were unlike to affect immediate neurosurgical management, and represent mainly differences in grading of astrocytomas and mixed gliomas. The cytological diagnostic criteria are discussed together with the main difficulties for the interpretation of this valuable approach to intra-operative neurosurgical diagnosis. PMID- 1308387 TI - Interleukin-6 and granulocyte macrophage-CSF in the cerebrospinal fluid from HIV infected subjects with involvement of the central nervous system. AB - We detected the cytokines interleukin-6 (IL-6) and granulocyte macrophage-CSF (GM CSF) by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC), and 20 subjects with other neurological diseases (OND). We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC. PMID- 1308388 TI - Evidence of preferential female prevalence of HTLV-I associated tropical spastic paraparesis in Bahia-Brazil. AB - In order to evaluate the prevalence of HTLV-I infection and its association with tropical spastic paraparesis (TSP) in Bahia, a Northeastern State of Brazil, CSF and sera from TSP patients and CSF and/or sera from some selected groups of individuals were studied. The results seem to indicate a higher prevalence of HTLV-I infection in women than men with TSP and among individuals of HIV risk groups. Some alterations of routine analysis of CSF can suggest HTLV-I infection in TSP patients. PMID- 1308389 TI - HTLV-I associated myelopathy in Salvador (northeastern Brazil). AB - Recent studies of tropical spastic paraparesis have confirmed the existence of human T-cell leukemia virus type-1 (HTLV-I) in several tropical areas of the world. In order to determine the role of HTLV-I as an etiologic agent of myelopathies in Salvador, we conducted a clinical and serological study in 43 patients with non-traumatic and non-tumoral myelopathies. We found 9 patients with HTLV-I associated myelopathy (HAM) which points to a new endemic area of HAM. PMID- 1308390 TI - [Recurrent bacterial meningitis]. AB - The study of CSF fistulae, and especially those involving otolaryngological anomalies, must be based on the search for the causative problem of recurrent meningitis. Congenital malformations, post-traumatic and post-operative situations or even diseases involving the cranial bones are basic causes that should be studied. Currently, cranial trauma is the most usual cause of CSF fistulae, with the possibility of recurrent bacterial meningitis. PMID- 1308391 TI - [Enteral hyperalimentation in acute cranio-cerebral injuries: replacement or diet therapy?]. AB - The authors raise a discussion on nutritional needs of severely traumatized patients under the currently knowledges about the pathophysiology of trauma, particularly in head injury patients. Special attention to the hypermetabolic and hypercatabolic states is given. Some considerations about dietary glucose and protein interactions are made. Finally, the authors expose the diet composition currently used in their institution. Routes and volumes for diet administration are commented. Questions about further studies in some areas of this field are also stated. PMID- 1308392 TI - [Spinal cord neuroschistosomiasis: clinical and laboratory evaluation of 5 cases]. AB - Schistosomiasis mansoni is an endemic disease in Brazil. Cases of nervous system schistosomiasis have been referred in our medical literature for the past forty years. In this report five cases of schistosomiasis of the spinal cord are studied. A review of the literature has been made and some clinical, laboratory and therapeutical aspects are discussed. PMID- 1308393 TI - [Meningioma of the olfactory groove and breast neoplasms: report of 2 cases]. AB - Two cases of olfactory groove meningiomas are presented in patients with breast cancer. Predominance of breast cancer and meningiomas in the age decades of the forties and the fifties, presence of steroid hormones receptors in both and prevalence of meningiomas in women are referred as significant correlations. Examination of the breast of women with meningiomas is recommended. Tomographic images are sometimes atypical, and a surgical intervention may be necessary. PMID- 1308394 TI - Cortico-basal ganglionic degeneration. A case report. AB - The case of a Brazilian patient with cortico-basal ganglionic degeneration (CBGD) is presented. Since three years ago, a 71-year old male displays asymmetric ideomotor apraxia, gait apraxia, cortical sensory impairment, myoclonus, limp dystonia and rigidity. His mental status is spared. There is neither consanguinity nor similar cases in his family. The differential diagnosis of CBGD is discussed. A brief review of the literature is made stressing the clinical and pathological features of CBGD. This disease is poorly known and probably underdiagnosed. Its diagnosis can be safely made based on clinical grounds. PMID- 1308396 TI - [Fibrous dysplasia of the temporal bone and cerebral occlusive vasculopathy: report of a case]. AB - Fibrous dysplasia is a benign disease with unknown etiology. Skull attempt may cause neurological disorders. The diagnostic can be made through radiological examination. A case of a patient with right temporal bone involvement with facial palsy, right parietal lobe infarctions and elevated anticardiolipin antibody titers is presented. Cerebral angiography showed occlusion of several cerebral arteries. Post mortem examination displayed recent myocardial infarction, ischemic cerebral softening, and generalized arteriosclerosis. The simultaneous occurrence of fibrous dysplasia and a probable anticardiolipin syndrome is commented. PMID- 1308395 TI - [Adrenoleukodystrophy: clinical and histopathological study of a case associated to the use of abortifacient agents in the second month of pregnancy]. AB - The authors report a case of adrenoleukodystrophy in a 8 years old male patient whose mother has taken several abortive drugs during the first three months of pregnancy. The disease was progressive starting with auditory, visual and mental disturbances, followed by neurovegetatives and motor changes with convulsion and fetal position. At the final stage the patient became blind, deaf, quadriplegic and dementiated. Death resulted from lung infection. The diagnosis was confirmed by the CSF, electrophysiological, radiological and necropsy findings. Necropsy changes in the brain and adrenal cortex are detailed. PMID- 1308397 TI - [Aneurysm of the distal portion of the posterior and inferior cerebellar artery in a child]. AB - The case of a 7-year-old boy presenting with recurrent episodes of subarachnoid hemorrhage due to a distal posterior inferior cerebellar artery aneurysm (PICA), successfully operated, is reported. The low incidence of intracranial aneurysms in the first decade of life and the rare occurrence of distal PICA aneurysms are unusual features of this case. The theories regarding the origin of intracranial berry aneurysms are discussed. PMID- 1308399 TI - [Clinical psychopathological types associated with smoking]. AB - Dependence and withdraw syndromes related with tobacco are mentioned. Clinical forms and types associated to tabagism considered are: psychopathic, borderline, neurotic, narcisic, psychotic, depressive, hedonic, and bulimic. Psychopathological and etiopathogenic factors of tabagism are listed. PMID- 1308398 TI - [Cystic oligodendroglioma and positivity of reactions for cysticercosis: report of a case]. AB - A case of a 32-year old male patient with complaints of frontal headache progressive decrease in visual acuity, altered behaviour, and positive results of immunological tests for cysticercosis performed on the cystic and cerebrospinal fluids is presented. After several clinical and surgical proceedings, the frontal craniotomy was indicated and a multi-lobulated cystic tumor was excised. Biopsy material revealed an oligodendroglioma invading the degenerated membrane of cystic wall. Some aspects related to the possible mechanisms involved in the association of oligodendroglioma with neurocysticercosis in the presented case are discussed. Three different types of conclusions may be reached: (1) neurocysticercosis may have acted as an oncogenetic factor for the oligodendroglioma; (2) the glycoprotein nature of the antigens of gliomas and cysticercosis and the similarity in the molecular weight range of their polypeptides may be responsible for the positivity of the reactions for cysticercosis in the cystic fluid; or (3) the association of oligodendroglioma with cysticercosis may be a simple coincidence. The present study strengthens the opinion that other pathologies should be looked for when clinical treatment of cysticercosis does not follow the expected course. PMID- 1308400 TI - [The neurologist and the medical literature: the process of endless education]. AB - To keep up to date with new advances in medical care and in the understanding of the disease process which affects their specific patients neurologists need to develop strategies for continuing education. They must be learners throughout their careers and the learning must be self-directed, active and independent. The best way to reach this goal is to devote regular time to the medical literature. However as the great volume of journal literature precludes clinicians from reading all of it, special tactics of scanning, selecting and reading medical articles are necessary. Priority should be given to original reports, meaning first-hand accounts of planned investigations, as they go through expert critical review before publication. This safeguard improves their clarity and usually keeps flawed research away. Furthermore one should read only original articles that have direct bearing on his own clinical practice and with scientific rigor making the results likely to be true. Employment of these rules may reduce the relevant literature to an affordable size. Extraction of these articles depend on the regular surveillance of high-yield, high-circulation general medical journals and the specialty and subspecialty journals which are relevant to one's practice. Review articles may be helpful either as an initial approach to a subject whose current knowledge is beyond one's usual domain or as a source of references of original articles. Meta-analysis or the integration and statistical combination of the results of previous research may be a further and a most important advantage of reviews. PMID- 1308401 TI - A study on the action of two calcium channel blockers (verapamil and flunarizine) upon an experimental model of tardive dyskinesia in rats. AB - Tardive dyskinesia (TD), a serious complications of neuroleptic chronic use, has no effective therapy yet. We performed an experiment to study the action on TD, of the calcium channel blockers (CCB) drugs, verapamil and flunarizine. We obtained the TD model in rats, administering haloperidol for a 21-day period. After this, the stereotyped movement induced by apomorphine was rated. The CCB drugs were administered in acute (in the 28th day) and chronic (for 8 days, after the 25th day) experiments. Acutely, verapamil increased the stereotyped behaviour, and promoted a reduction of it in the chronic experiment. The results suggest that CCB drugs should be tested in clinical trials of TD. PMID- 1308402 TI - Electrocardiographic findings in acute cerebrovascular hemorrhage. A prospective study of 70 patients. AB - Seventy patients with hemorrhagic stroke were prospectively evaluated regarding the electrocardiographic abnormalities observed within the first 48 hours of the ictus. Group I comprised 55 patients with spontaneous cerebral hemorrhage, and group II 15 patients with subarachnoid hemorrhage. Patients taking cardiac drugs (beta blockers, calcium-channel blockers, inotropic drugs) or with severe metabolic/electrolyte disturbances were excluded. The most common ECG abnormality was a prolonged Q-Tc interval: group I, 37 (67.2%); group II, 8 (53.3%). Only 4 (7.2% patients of group I and no patient of group II had a normal ECG. No relation was found between the site of the intracerebral hematoma and the occurrence of any particular ECG change. A prolonged Q-Tc may be related to the development of severe cardiac arrhythmias observed in some patients with acute cerebral hemorrhage. PMID- 1308403 TI - [Extradural hematoma: comparative radiological study between comatose and non comatose patients]. AB - A series of 129 patients harbouring extradural hematomas was analysed considering the neurological state immediately before operation as the most consistent variable. Seventy eight patients were considered to be comatose (Group I) and 51 were noncomatose. Among the comatose group, 30 were investigated with computerized tomography (23.3% mortality, 50% good results), 31 were submitted to angiography (48.3% mortality, 38.7% good results), and 17 were operated based on the neurological examination and skull radiography (47% mortality, 35.2% good results). The presence or absence of skull fracture and the density of hematoma did not change the final outcome. Associated intracranial lesions increased the mortality and lowered the good results in both groups. Frontal hematomas (10 cases) in the comatose group were associated with high mortality (52.6%) due to bad neurological state (Glasgow 3-5) and to isolated or multiple intracranial associated lesions (6 patients). PMID- 1308404 TI - [Incidence of peri-intraventricular hemorrhage in preterm newborn infants with birth weight less than 1500 gms: evaluation of brain ultrasonographic studies and necropsy]. AB - From January to December 1986, 120 preterm infants were born with birth-weight under 1500 gm. Eighty-five infants were included in the study group either because they had a cranial sonographic evaluation or a necropsy. The mortality rate was 70% for the study group, but was 52.5% for the whole period. The sonographic examination was performed in 41 infants. The incidence of periventricular-intraventricular hemorrhage (PIVH) was 42.3%. Twenty-three cases had PIVH grade II (63.8%), 10 grade I (27.7%), and 3 (8.3%) grade IV. Thirteen infants had sonographic and necroscopic examinations. We observed a total agreement between sonographic and necroscopic diagnosis in 9 cases (69%). Two cases were classified as partial agreement as they differed only in the grading of PIVH, whereas in two cases there was a false negative diagnosis in the ultrasound examination. The interval between the examinations in these two false negative cases was 53 and 20 days, respectively. We conclude that the incidence of PIVH found in our study is comparable to that of the literature and that cranial ultrasonography is a sensitive neuroimage technique for the diagnosis of PIVH in the newborn preterm infant. PMID- 1308405 TI - [Neonatal bacterial meningitis: etiological agents in 109 cases during a 10 year period]. AB - The etiology of purulent meningitis was investigated in 109 newborn infants admitted in a neonatal intensive care unit throughout a ten year period. Bacterial pathogens were isolated from the CSF in 57 (52.2%) neonates. There was a predominance of Gram-negative bacilli isolated in 38 (34.9%) neonates. Gram positive cocci were isolated from CSF in only 12 (11.0%) neonates. Microorganisms associated with nosocomial septicemia and meningitis in neonates--Klebsiella sp, Salmonella sp. Enterobacter sp, Pseudomonas sp, Flavobacterium meningosepticum and Serratia marcescens--were responsible for presumptive etiology in 38 (49.3%) among 77 patients with positive cultures in "closed sites". They were isolated from 22 (57.0%) neonates with prior hospitalization but only from 12 (34.3%) neonates coming directly from their households (chi 2 = 4.08; p < 0.05). The mortality rate was significantly higher in patients with positive CSF cultures (47.4%) in comparison to patients with negative cultures (18.4%) (X2 = 5.01; p < 0.05). It is possible to conclude that Gram-negative bacilli, many of them of hospital origin, are the major pathogens in this study. An improvement on neonatal health care and a scrupulous control of neonatal nosocomial infections are recommended. PMID- 1308406 TI - [Immunosuppressive treatment in multiple sclerosis]. AB - An open, retrospective, uncontrolled study was carried out to evaluate efficacy and tolerability of immunosuppressive therapy used in the period 1982-1990 in patients with clinically definite multiple sclerosis. Of 42 patients 43% were treated with one drug, and the others with more than one. Tolerability was evaluated after at least 6 months of therapy in 6 patients on prednisone, 26 on azathioprine, 17 on methyl-prednisolone and 15 on cyclophosphamide pulses. Reversible mild or moderate side-effects were noted in 54% of the patients on azathioprine, leading to change in dose or withdrawal. There were similar side effects in 83% of the patients on prednisone, 40% of those on cyclophosphamide, and in 12% of those on methylprednisolone. Efficacy was evaluated in 15 patients with a follow-up of at least 2 years, measured by objective scales. The results indicated therapy appeared to arrest progress of disability. We conclude that this study supports the use of immunosuppression in selected cases with rapidly evolving neurological deficits. PMID- 1308407 TI - [Comparative study of immunoenzyme tests ELISA-G and ELISA-M, indirect immunofluorescence, and complement fixation in the diagnosis of human cysticercosis]. AB - A comparative study of four immunological tests used for anti-Cysticercus antibodies detection--Enzyme-Linked ImmunoSorbent Assay IgG (ELISA-G) and IgM (ELISA-M), indirect immunofluorescence (RIFI) and complement fixation (RFC)--was made in serum and cerebrospinal fluid (CSF). 539 patients with symptoms suggesting cysticercosis, 450 relatives of these patients and 133 normal people (control group) were examined. 1122 serum samples and 120 CSF samples were analysed by ELISA-G and RIFI, 83 sera and 60 CSF also by RFC, and 28 CSF by ELISA M. 5.2% serum samples were reagent in ELISA-G and RIFI, and 3.5% of them had discordant results. All control group sera were negative. The same tests in CSF were positive in 16.7% and had discordant results in 7.5%. ELISA-G and RIFI in serum and CSF had concordant results in 89.6% (17.7% were positive). ELISA-G, RIFI and RFC had concordant results in 54.2% sera (16.9% positives) and in 81.7% CSF (11.7% positives). When ELISA-G and RIFI were negative, RFC was positive in 41.0% sera and 11.7% CSF. ELISA-G and ELISA-M had concordant results in 78.6% CSF. When these results were discordant ELISA-G was positive in 10.7% and ELISA-M in another 10.7%. It is necessary to use concomitantly several immunological tests for anti-Cysticercus antibodies detection in serum and in CSF, in attempting to reach correct diagnosis. PMID- 1308408 TI - [Epilepsy and public education]. AB - The social problems experienced by persons with epilepsy become increasingly apparent to those who work closely with group associations. The objective of our study was to obtain information on personal attitudes and knowledge about epilepsies. Primary and high-school teachers and professors (medical and non medical areas) were submitted to a questionnaire which was designed to obtain this information. We concluded that most professors (including those of medical areas) do not know enough about epilepsies. We believe that problems which are perceived by epileptics regarding social aspects may be softened through improved education of the community in general. Continued education of medical practitioners, professors, teachers, patients and their families leads to a positive attitude towards epilepsies, which are essential and may help to improve life quality and the patient's medical treatment. PMID- 1308409 TI - [Stereotaxic biopsy for primary lymphomas of the central nervous system]. AB - Primary lymphomas of the CNS are rare. However the incidence of these lesions has increased recently. These tumors are often situated in the thalamus and basal ganglia, but can be multifocal. The treatment for primary CNS lymphoma is radiotherapy alone or in association with chemotherapy. Because the associated morbidity is very low stereotactic biopsy is an ideal method for determining the histologic diagnosis in patients with suspected CNS lymphoma. The authors present a study of 49 patients with primary CNS lymphomas in which a stereotactic biopsy was performed. PMID- 1308410 TI - [Plasmapheresis in neurology. Critical analysis of indications and protocols]. AB - Therapeutic plasmapheresis (plasma exchange) in neurology is a matter of discussion. We review the main articles on clinical trials, both controlled and uncontrolled, trying to establish the efficacy and safety of the procedure. Humoral aspects involved in the genesis of the disorder play an important role for its indication in the present time. In myasthenia gravis indications for plasmapheresis are established: in the preparation for thymectomy, in patients with respiratory insufficiency and requiring respiratory prosthesis, after long immunosuppression therapy with rebound effect, when all other forms of therapy failed, and in neonatal myasthenia gravis with special technics. We discuss the indication of plasmapheresis in Guillain-Barre syndrome, multiple sclerosis, chronic inflammatory demyelinating polyneuromyelopathy, HTLV-1 myelopathy, HIV peripheral neuropathy and myelopathy, paraproteinemias, polymyositis, and dermatomyositis. Indications for other diseases are mentioned. Reference is made to the results we observed in 31 cases followed consecutively at Hospital dos Servidores, Rio de Janeiro, from June 1984 to June 1990. In our series 26 were myasthenic patients, 4 patients presented Guillain-Barre syndrome, and 1 multiple sclerosis. Therapeutic plasmapheresis protocols suggested by us are summarized. PMID- 1308411 TI - Coma and death in unrecognized Wernicke's encephalopathy. An autopsy study. AB - Eleven out of 36 autopsied cases of Wernicke's encephalopathy had developed coma. None of these patients had the diagnosis during life. There were six men and five women with ages ranging from 26 to 50 years (mean 36.6). Seven of these patients were heavy drinkers, three exhibited signs of severe malnutrition, whereas one was being evaluated for a disseminated gastric cancer and one was in treatment of hyperemesis gravidarum. Two patients were brought to the hospital after found unconscious at home. Neuropathological examination disclosed gross changes in the mammillary bodies in eight cases and microscopic changes in all cases. In one case there was atrophy of the anterior superior part of the vermis. Petechial hemorrhages were observed particularly in the walls of the third ventricle. Microscopically there were in addition to hemorrhages, glial proliferation, endothelial hypertrophy and necrosis of nerve cells and myelin. Central pontine myelinolysis was observed in one case. Wernicke's encephalopathy is a clinically underdiagnosed condition. Coma may mask its classical clinical picture or even be the sole manifestation. Although coma points to a poor outlook it may be reversed by thiamine administration. Any patient with coma of unknown etiology should be given parenteral thiamine. PMID- 1308412 TI - [Krabbe's disease (globoid cell leukodystrophy). Apropos of 5 cases]. AB - A clinical study on five cases of Krabbe's disease (globoid cell leukodystrophy) was performed. A final diagnosis was done either with post-mortem study (two cases) or by enzymatic assays carried on cultured fibroblasts (two cases). Peripheral nerve biopsy for electron microscopy was performed in all cases, and the ultrastructural alterations characteristics of Krabbe's disease were always found. The authors emphasize the suggestive clinical and laboratory data which enable the diagnosis of Krabbe's disease in the absence of the ultrastructural exam of peripheral nerve, or the enzymatic assays not performed in this country. PMID- 1308413 TI - [Spinal cord cysticercosis: report of 2 cases, review of the literature, and comments on its pathogeny]. AB - A case of spinal intramedullary cysticercosis in a 13-year-old Brazilian female and a case of spinal leptomeningeal infestation by cysticercosis in a 51 year-old Brazilian female are presented. A review of 95 published cases of medullar cysticercosis since 1856 shows the incidence of this condition. Extramedullary forms are explained by the downward migration of larvae from the cerebral to the spinal subarachnoid space and most larvae are expected to be stopped in the upper portions of the spinal canal due to peculiarities of the anatomy of the spinal cord. PMID- 1308414 TI - [Intracranial dissecting aneurysms of the posterior circulation: report of 3 cases and review of the literature]. AB - Dissecting aneurysms of cerebral arteries are unusual causes of stroke. The carotid system is the commonest site of this pathology, the vertebral arteries are less involved and dissection of the basilar artery is rare. The authors report three cases of arterial dissection of the vertebrobasilar system, two of the vertebral arteries and one of the basilar artery. An extensive review of the literature is presented. The clinical picture of dissection of vertebrobasilar system was inespecific but pain was a prominent symptom, though had not occurred in the site of the arteries involved. The pain was suggestive of subarachnoid hemorrhage. Associated or risk factors were mild trauma, migraine and high blood pressure. The angiographic findings were suggestive, however just the "double lumen" has been considered pathognomonic. The prognosis is variable. It was benign in case 3, left sequela in case 2, and case 1 rebleed fatally. PMID- 1308415 TI - [Traumatic extradural hematoma in childhood and normal early computed tomography: report of 2 cases]. AB - The cases of two children with traumatic extradural hematoma with an early normal CT scan are reported. Consciousness impairment occurred in them respectively 20 and 60 hours after admission, and CT at this occasion evidenced extradural hematoma. Serial neurological examinations are recommended for children with large traumatic cephalohematoma associated or not to skull fracture and in whom an initial early CT was normal, since they can lately develop extradural hematoma. PMID- 1308416 TI - Traumatic callosotomy. AB - In a 33 years-old epileptic woman with a traumatic impact to the vertex, clinical and radiological studies (skull X-R, CT and MRI) disclosed an extensive callosal section under the topography of the falx, associated to fronto-basal contusions. There was a significant improvement in the epileptic syndrome. No interhemispheric disconnection syndrome could be determined, which is compatible with the posterior regions of the corpus callosum having been spared. This is, to the best of our knowledge, the most extensive callosal injury documented by MRI to date. PMID- 1308417 TI - [Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of a case and review of the literature]. AB - Progressive supranuclear palsy (PSP) was first recognized as a distinct syndrome by Richardson, Steele and Olszewski roughly a quarter century ago. Subsequent clinical experience has corroborated and enlarged their original observations. PSP has become familiar as a chronic progressive disorder with extrapyramidal rigity, bradykinesia, gait impairment, bulbar palsy, dementia and a characteristic supranuclear ophthalmoplegia. It is a significant cause of parkinsonism and its etiology remains obscure. The case of a patient from Santa Catarina who presented definite clinical evidences of this syndrome is reported. This is the first description in this southern Brazilian State, where at least 50 more patients should exist, if we may extrapolate the prevalence rate of this condition in developed countries to this well developed area of Brazil. A review of the literature was undertaken with emphasis on recent clinical and therapeutic aspects of PSP. PMID- 1308418 TI - Acute central nervous system infection by Trypanosoma cruzi and AIDS. AB - The acute infection of the CNS by Trypanosoma cruzi acquired by blood transfusion is uncommon. The concomitance of AIDS in the patient reported shows the importance of cellular immunity in restriction of this parasite, and reinforces the problem of blood transfusion in endemic zones. PMID- 1308419 TI - Machado de Assis's epilepsy. AB - Machado de Assis (1839-1908) is considered the most important Brazilian writer and a great universal literary figure. Little is know about his medical, personal and family history. He hid his "disease" as much as possible. Machado referred to "strange things" having happened to him in his childhood. He described seizures as "nervous phenomena", "absenses", "my illness". Laet observed a seizure and described it as: "... when Machado approached us and spoke to me in disconnected words. I looked at him in surprise and found his features altered. Knowing that from time to time he had nervous problems, ... and only permitted Machado take the Laranjeiras Street car, when I saw that he was completely well". A photographically documented seizure is shown. Alencar wrote, "The preoccupation with health was frequent: either he was having the consequences of a fit or was foreboding one". It is clear that Machado presented localized symptomatic epilepsy with complex partial seizures secondarily generalized of unknown etiology. The seizures which began in infancy or childhood had remission in adolescence and then recurred in his thirties and became more frequent in his later years. His depression got markedly worse with age. In our opinion, the greatest consequence of Machado's epilepsy, was his psychological suffering due to the prejudice of the times. Despite this Machado showed all his genius, which is still actual and universal. PMID- 1308420 TI - Clinical and morphological study of calf enlargement following S-1 radiculopathy. AB - Calf enlargement following sciatica is a rare condition. It is reported the case of a 28-year-old woman who complained of repeated episodes of lower back pain radiating into the left buttock and foot. One year after the beginning of her symptoms, she noticed enlargement of her left calf. X-ray studies disclosed L5-S1 disk degeneration. EMG showed muscle denervation with normal motor conduction velocity. Open biopsies of the gastrocnemius muscles were performed. The left gastrocnemius muscle showed hypertrophic type 2 fibers in comparison with the right gastrocnemius. Electron microscopy showed mildly increased number of mitochondria in these fibers. A satisfactory explanation for denervation hypertrophy has yet to be provided. PMID- 1308421 TI - [Hemifacial spasm and basilar impression associated with Arnold-Chiari deformity. Report of a case]. AB - The authors report a case of symptomatic basilar impression and Arnold-Chiari malformation being presented as the first symptom of hemifacial spasm. The surgical treatment of the malformation resulted in improvement of the clinical manifestation with reduction of the hemifacial spasm. The need for the aetiological therapy for the hemifacial spasm is emphasized, before symptomatic treatment with botulinum toxin is tried. PMID- 1308422 TI - [Partial motor status epilepticus. Primary form provoked by eye closure]. AB - We report the case of a young female patient with photosensitive primary epilepsy who presented partial motor status epilepticus provoked by the act of shutting the eyes. Clinical, EEG and neuroimage data are presented and discussed. PMID- 1308424 TI - Danazol. A new perspective in the treatment of HTLV-1 associated myelopathy (preliminary report). AB - We investigated the efficacy of danazol treatment in eight patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Treatment with danazol yielded clinical improvement of urinary control and gait disturbances in 7 out of the 8 patients. The improvement was noted within 15 days of danazol administration. Analysis of factors of relevance to the clinical improvement with danazol showed that the beneficial response was preferentially found in females. PMID- 1308423 TI - [Macroprolactinoma at 6 years of age: diagnostic difficulties]. AB - Prolactinoma is rare in childhood and adolescence. The earliest known diagnosis was reported in a patient at 8 years of age. We report the case of a sellar tumor found in a 6 years old girl. After a long symptomatic period she was brought for treatment. At this time she had partial papillar atrophy, hyperprolactinemia, and diminished reserve of growth hormone and cortisol. Due to rapid visual deterioration, she was submitted to a frontotemporal craniotomy for suspected craniopharyngioma. The tumor tissue immunohistochemistry was positive for prolactin. It is concluded that prolactinoma must be considered in differential diagnosis of sellar tumors in childhood since it benefits from a less aggressive therapy. PMID- 1308425 TI - [In memoriam: Deolindo Augusto de Nunes Couto (1902-1992)]. PMID- 1308426 TI - [In memoriam: Nunjo Finkel (1926-1992)]. PMID- 1308427 TI - Advanced trauma life support. A time for reappraisal. AB - The experience of Advanced Trauma Life Support training received by three anaesthetists is discussed with particular reference to the teaching of airway management, the grade of staff who should attend the present courses and the relevance to the British hospital system. We conclude that these courses are useful but limited by their inflexibility and failure to recognise the difference in skill mix in the British setting. PMID- 1308428 TI - Improving public health care: lessons on governance from five cities. AB - Policy-oriented investigations into public health care delivery have been limited, especially during the Reagan era of competition and profit-based health care, when the inner city was essentially forgotten. In this study, policymakers toured five urban public health care systems in different parts of the country to promote consideration of a new governance for Chicago and Cook County's complicated and uncoordinated care for the medically indigent. A comparison of patterns of governance revealed strengths and weaknesses of each model. Local leadership and the political will to evolve a system of care, with clear connections between the public and private sectors, account for each city's relative success in addressing mounting needs of inner-city populations. PMID- 1308429 TI - A pediatrician's view. The pursuit of thinness. PMID- 1308430 TI - [The epidemiological characteristics of influenza in a large urban center (B.) of Romania in 1991]. AB - The peculiarities of the 1991 influenza epidemics in a big urban centre (B.) of Romania were evaluated through clinical and epidemiological active survey and laboratory assays. The results revealed the low rate of endemic morbidity and its significant risk during the fourth trimester as compared to the first, the important implication of the infant population in maintaining the endemic morbidity and of the less than one year old children in the seasonal peaks of the first and fourth trimesters. The laboratory assays revealed the simultaneous circulation but with variable intensity of type A(H3N2), A(H1N1) and B influenza viruses, inducing a high humoral specific protection level in the population. So the risk is low of an important epidemics during 1992. The opportunity is discussed of the prophylactic vaccination with type A(H3N2), A(H1N1) and B circulating strains of all high risk groups, especially of the preschool children from collectivities. PMID- 1308431 TI - [Epidemiological and virological research on influenza and viral respiratory infections in the southeastern region of Romania in the cold season of 1991 1992]. AB - Investigations pointed out the high level of respiratory diseases and pneumonias in children, especially in the youngest ones (0-1 year-old) during all the surveyed period. An influenza outbreak during the second half of February was registered in the infantile population--school and low-age children--which gave most of the cases. Serology and isolations incriminated an influenza virus related to the A/Beijing 353/89 (H3N2) strain. Isolations worked out after the influenza epidemics pointed out circulation of parainfluenza and adenoviruses. The necessity is emphasized of the anti-influenza vaccination of low-age children. PMID- 1308432 TI - [The efficacy of a combined therapy against herpes virus genital infections]. AB - A complex immuno-chemical therapy (inhibition of viral replication, stimulation of cell mediated immunity, interferon induction) was applied to 75 patients with herpes virus genital infections. Treatment was followed by complete recovery in 66.7% of the subjects and by considerable reduction of relapse frequency and of pain in the others. PMID- 1308433 TI - [Gene amplification for the diagnosis of HIV infection]. PMID- 1308434 TI - [The chemical therapy of HIV infections. Strategies, results, prospects]. PMID- 1308435 TI - A sex-specific analysis of correlates of homicide victimization in United States cities. AB - A considerable amount of research has been devoted to determining structural correlates of homicide across places in the United States. However, recent research has found that general correlates may not hold when homicide rates are disaggregated into analysis of specific groups. Adopting a public health approach, we explore the possibility that male and female rates of homicide victimization may show differential patterns of association with selected social structural risk factors across a sample of U.S. central cities. The results show that both male and female homicide victimization is related to a general set of factors derived from the theoretical framework of social disorganization. At the same time, it is found that these factors are better predictors of male than female homicides. Suggestions are made for research to discern additional factors, perhaps distinct from those of men, related to the rather considerable variation in the prevalence of female homicide across communities in the United States. PMID- 1308436 TI - Relationships among marital investment, marital satisfaction, and marital commitment in domestically victimized and nonvictimized wives. AB - The present investigation examined the association between marital investment, marital satisfaction, and commitment to marriage among physically abused women. We applied an investment model and a social learning model to understanding victimized wives' satisfaction and commitment to stay married. Thirty wives who reported physical abuse and 58 nonabused wives completed measures of marital stability, investment in marital problem solving, and dyadic adjustment. Investment in marital problem solving was assessed by having subjects indicate how much energy that they have put into solving 34 common marital problems and whether their efforts were successful or not successful. Consistent with a social learning model but counter to an investment perspective, correlational and multiple regression analyses for each group revealed that failed investment was significantly related to lower, not greater, commitment. Group differences also emerged. Whereas nonabused wives' commitment was related to their dyadic adjustment abused wives' commitment was related to their level of failed investment. Results are consistent with the notion that women may remain in abusive relationships because of psychological entrapment. PMID- 1308437 TI - Predictors of dating violence: a multivariate analysis. AB - A multivariate approach was used to determine the pattern of predictors associated with engaging in dating violence. Predictors were selected whose relationship to dating violence has been established by earlier research: attitudes toward violence, sex-role attitudes, romantic jealousy, general levels of interpersonal aggression, verbal aggression, and verbal and physical aggression received from one's partner. Participants included 305 introductory psychology student volunteers (227 females and 78 males) who completed a set of scales related to dating relationships. Expecting different patterns of predictors to emerge for men and women, we performed separate multiple regression analyses for each. Of the set of predictors employed, receipt of physical violence from one's partner emerged as the largest predictor of expressed violence for both men and women. In addition, higher scores on attitudes toward violence and verbal aggression, and less traditional sex-role attitudes emerged as significant predictors of expressed violence for men. For women, less accepting attitudes toward violence, more traditional sex-role attitudes, feelings of romantic jealousy, higher general levels of interpersonal aggression, and verbal aggression were predictive of expressed violence. The implications of our findings for future research are discussed. PMID- 1308438 TI - Joint consequences of parental alcoholism and childhood sexual abuse, and their partial mediation by family environment. AB - This study investigated the effects of childhood sexual abuse and parental alcoholism in a sample of university women. Current symptoms of anxiety and depression were measured together with retrospective reports of subjects' families of origin. Using a 2 x 2 factorial design, main effects on symptoms were obtained for sexual abuse and parental alcoholism, but their interaction was not significant. With respect to family environment, a history of sexual abuse was associated with perceptions that families of origin had less cohesion, more conflict, less emphasis on moral-religious matters, less emphasis on achievement, and less of an orientation towards intellectual, cultural, and recreational pursuits. Similarly, subjects who had alcoholic parents reported less family cohesion, more conflict, and less emphasis on moral-religious matters. Results of analyses of covariance suggested that family environment was a mediator of current symptoms of anxiety, but not symptoms of depression. PMID- 1308439 TI - Multiple perspectives on groupwork with children of battered women. AB - As this century ends there continues to be little public attention devoted to child witnesses of woman abuse and few social programs exist to meet their needs. This article presents the findings of a qualitative evaluation of a group program for children of battered women. Interviews were conducted with 16 mothers, 5 fathers, 9 group leaders, and 30 children who participated in 8 groups. Data also included observations of one complete group process (10 groups and 3 family sessions). Both intended and unintended results are presented and recommendations for practice are discussed. PMID- 1308440 TI - Trends and patterns of justifiable homicide: a comparative analysis. AB - This paper reports the first national level analysis of police and citizen justifiable homicides for a twelve year period. Utilizing data from the Comparative Homicide File, trends and characteristics of police and citizen justifiable homicides are described and reviewed. Particular emphasis is given to comparing justifiable homicides to criminal homicides. The results establish that while similar to criminal homicide, police and citizen justifiable homicides differ significantly in terms of factors such as circumstance, relationship, weapons, and racial characteristics. PMID- 1308441 TI - [A new stage for the journal Atencion Primaria]. PMID- 1308442 TI - [The prescription of intramuscular injectable drugs: a comparative study]. AB - AIMS: To find out the personal characteristics of patients who receive intra muscular medication. To examine those illnesses where this treatment is used. To compare the number of intra-muscular treatments prescribed with the nature of the medication, according to a model of Primary Care and to the doctors training. DESIGN: We are dealing with an observational study, in which a questionnaire was used to find patients' characteristics and the prescription given. SITE. The present study was carried out in the Ibiza Health Centre and two old-fashioned out-patient clinics in our Health Area. PATIENTS AND OTHER PARTICIPANTS: The population under study consisted of all those patients above the age of 7 who received intramuscular treatment during the period of the study (October, November and December, 1990). INTERVENTIONS: There were no interventions, as this was an observational study. MEASUREMENTS AND MAIN FINDINGS: The intra-muscular method of administration was used more in women, people over 50 and those with a very low cultural level. The majority of patients (59.66%) believed that this method was superior to enteric treatments. This method was more often used in out patient clinics than in the Health Centre (p < 0.01). In the Health Centre less medication treating the Locomotive System (p < 0.001) and more dealing with the Centre Nervous System (p < 0.02) was prescribed. In out-patient clinics more antibiotics, either in combination with each other or with other products, were prescribed (p < 0.01). CONCLUSIONS: In the Health Centre the intra-muscular method was used less. Additionally, a smaller proportion of the medication given was intrinsically useless or of unacceptably low value. PMID- 1308443 TI - [Vaccination against hepatitis B]. PMID- 1308444 TI - [The influence of a prior appointment on primary care consultations in the Murcia region]. AB - AIM: Analysis of how the prior appointment system affects various indicators of attendance. DESIGN: A multi-centered intervention study. SITE. Faculty of Medicine. Department of Social-Health Sciences. PATIENTS AND OTHER PARTICIPANTS: Patients seen in the general consulting-rooms of urban and rural Health Centres during the same months in two successive years, i.e. before and after setting up the prior appointment system. INTERVENTIONS: Introduction of the prior appointment programme (a consultation, with the hour and date arranged beforehand). Questionnaire given to the patient at the end of the consultation. MEASUREMENTS AND MAIN FINDINGS: The personal variations of age and sex, and also of those relating to the medical side were compared by means of the questionnaire, before and after the introduction of the prior appointment system. Significant differences were only seen in relation to hospital referral, which tripled; and to the number of prescriptions per person, which increased. CONCLUSIONS: The prior appointment system has meant less waiting-time for patients and a rationalisation of consultation time; but it has not substantially altered the content of the consultation. PMID- 1308445 TI - [Knowledge of the hygiene habits of schoolchildren: a course of urban collaboration in health]. AB - AIM: To study the hygiene habits of schoolchildren in Santa Maria de Gracia (an urban site) and La Nora (a rural site), both in Murcia. This stemmed from an initiative of the Health Councils of these places, with the aim of later developing an effective project of Health Education. The Community was conceived as the main player in the Health-Illness process: passive behaviour models were thus abandoned. DESIGN: This was a transversal study of the hygiene customs of school-children from Second and Seventh Grade E.G.B. (General Basic Education: from 8 to 13) in the rural area; from Second and Fifth Grade EGB, from Second Grade BUP (Baccalaureate: from 14 to 16) and from the Second Course of Second Grade FP (Professional Formation) in the urban area. Questionnaires covered the whole of the above population. Crosses according to age, sex and the rural or urban environment were made. PARTICIPANTS: Professionals from both the Primary Care Teams, from Educational Centres, from the Department of Socio-Health Sciences of the Faculty of Medicine and schoolchildren interviewed. INTERVENTIONS: Using a participatory methodology, a questionnaire was designed and answered by a total of 1,182 students, belonging to 13 Educational Centres. MAIN FINDINGS: There are shortcomings open to improvement in practically all areas of hygiene habits; with important differences, in particular customs, between boys and girls, between town and country and between younger and older students. PMID- 1308446 TI - [Vaccination against hepatitis B at the Palma-Palmilla Health Center of Malaga]. AB - AIM: To describe the results of a programme of anti-hepatitis B vaccination of high-risk groups. DESIGN: Observational descriptive study, of a retrospective character. SITE. At a community level within the confines of Primary Care in the Palma-Palmilla (Malaga) Health Centre, between June 1989 and March 1990. PATIENTS AND OTHER PARTICIPANTS: Individuals with a high risk of Hepatitis B infection, according to a modified CDC (Centre for Diseases Control) scale. The subjects were found during their attendance as patients and from among the Health Centre staff. INTERVENTIONS: The second generation vaccine developed by genetic engineering (Engerix B) was used. It was administered by intramuscular injection in a dosage of 20 mcg to those weighing more than 25 kilos; and of 10 mcg to those weighing less than 25 kilos. The vaccination pattern was of three doses in months 0, 1 and 6, followed by a monthly sero-conversion check. MEASUREMENTS AND MAIN FINDINGS: 169 individuals began the vaccination programme: 17.7% were health workers and 81.6% lived with carriers of the virus. 87.6% completed the vaccination programme. Sero-conversion in the individuals controlled was 95.5%. Only five patients were sero-negative after the third vaccination. Of these four cases achieved sero-conversion after a fourth or fifth dosage. CONCLUSIONS: We found there was a high rate of sero-conversion; and also high acceptance of the programme by those living with a carrier. PMID- 1308447 TI - [Mental health referrals from a primary care team]. AB - AIM: Study of patients' referrals from a Primary Care Team (PCT) to a Mental Health Centre. DESIGN: Descriptive study. PLACE: Health Centre. PATIENTS AND OTHER PARTICIPANTS: Patients seen in the Health Centre consulting-rooms, who are then referred to the Mental Health Centre. INTERVENTIONS: The details of age, sex, socio-economic levels, cause of referral, quality of information on the referral form, diagnosis made in the Mental Health Centre and the later development of the case, were all analysed. MEASUREMENTS AND MAIN FINDINGS: A total of 90 referrals were studied. There were significant differences between the average ages of men and women. A large number of referrals fell into the 20 40 and under-sixteen age groups. The most frequent diagnoses were of upsets in the frame of mind disturbances with a source in infancy. 90% of the referral forms fulfilled the minimum level of information necessary. CONCLUSIONS: The importance of ongoing Mental Health Education of Primary Care professionals, in order to increase the quality of Health Care delivered to the population. PMID- 1308448 TI - [The follow-up of pregnancy in the province of Salamanca]. AB - AIM: To discover the level of health care accorded to pregnant women, the type of professional who attends them, and to what extent guidelines proposed for monitoring pregnancies are carried through. DESIGN: A transversal, retrospective, observational study: without a control and with a random sample. SITE. The data were obtained in a Public Hospital and came from women who had been monitored at all levels of health care, whether public or private. PATIENTS: The study was of all the women who gave birth in the General Hospital over a period of three months. MEASUREMENTS AND MAIN FINDINGS: An interview was administered to 500 pregnant women. It was found that the number of pregnancies attended to at the Primary Care level is small (9% in Health Centre consultations and 6% by the General Practitioner). The entry of pregnant women into the Health System is late: 48% from the fourth mont. In a high percentage of cases, no explorations of the neck of the womb are made; nor are certain analytic tests (e.g. renal and liver function tests and urinary cultures) and various complementary checks made. CONCLUSIONS: 1) Health Education programmes must be initiated at the Primary Care level, in order to draw in at an early stage the pregnant woman. 2) There is a need to use guidelines for pregnancy and develop programmes of ongoing training for Primary Care professionals, in order to improve the quality of health care during pregnancy. PMID- 1308449 TI - [The diagnosis, treatment and follow-up of the hyperlipidemic patient in primary care]. PMID- 1308451 TI - [The treatment of hypercholesterolemia in high-risk individuals, women and the elderly]. PMID- 1308450 TI - [Enteropathic arthritis]. AB - AIM: Description of a clinical case of enteropathic arthritis. DESIGN: Descriptive study. SITE. Health Centre. PATIENTS AND OTHER PARTICIPANTS: A clinical case is described, starting with back pain where X-rays perceive no irregularity. Later a diagnosis of Crohn's disease is made. Finally lesions characteristic of anchylo-poyethic spondylitis appear. INTERVENTIONS: Corticosteroid treatment. MEASUREMENTS AND MAIN FINDINGS: Clinical investigations and complementary diagnoses. CONCLUSIONS: Way in which spondylitis presents, with no clear X-ray indications. Importance of closely following the development of this type of patient. PMID- 1308452 TI - [Proposals for the development of a system of continuing education in primary care]. PMID- 1308453 TI - [The treatment of uncomplicated lower-urinary tract infection: a single dose of trimethoprim as opposed to 10 days with pipemidic acid]. PMID- 1308454 TI - [A case of amyotrophic lateral sclerosis]. PMID- 1308455 TI - [Vaccinating in school: the limits of expediency]. PMID- 1308456 TI - [The customized use of bibliographic data bases]. PMID- 1308457 TI - [The reliability of a delayed reading of reactive strips of capillary blood glucose]. PMID- 1308458 TI - [The characteristics and appropriateness of the demand for emergency care at a health center]. PMID- 1308459 TI - The immune destruction of red cells. PMID- 1308460 TI - A new low-frequency platelet alloantigen, Vaa, on glycoprotein IIbIIIa associated with neonatal alloimmune thrombocytopenia. AB - We describe platelet alloimmunization which caused severe thrombocytopenia in a neonate and could only be detected by testing the father's platelets. The platelet-specific antibodies were identified by a monoclonal antibody-immobilized platelet protein assay (MAIPA) using monoclonal antibodies against glycoprotein (GP) IIbIIIa complex (AP2 and 2G12). The previously described alloantigen systems on the GPIIbIIIa complex (HPA 1, HPA 3 or HPA 4) were not responsible for the reaction. In addition the newly described private platelet antigen Sra was not identical to the antigen. The antigen is therefore different from all known platelet alloantigens and was designated Vaa. The antigen was present on the platelets of the affected child. Family studies showed that the platelet antigen was transmitted as an autosomal dominant trait in three generations. No Va (a+) individuals were found in a population study of 250 blood donors, which indicates that the antigen is of low frequency in the Finnish population. The Va antigen was not detectable by immunoblot analysis, which suggests that the epitope may not be a linear peptide structure. The antigen was also destroyed by solubilization of platelets. Thrombin activation of platelets, known to increase the expression of GPIIbIIIa on platelets, did not increase the number of binding sites for anti-Vaa antibodies to the extent observed with anti-HPA 1a binding. PMID- 1308461 TI - The definition of refractoriness to platelet transfusions. AB - The relationship between the 1 and 20 h post-transfusion platelet count and three parameters used to define refractory transfusions, namely the corrected increment (CI), platelet increment (PI), and percentage platelet recovery (%REC), was studied in 437 non-HLA matched platelet transfusions given to 102 patients with bone marrow failure. The percentage agreement between common definitions of refractoriness was calculated based on these parameters. As the maintenance of platelet counts above 20 x 10(9)/l is a relevant clinical goal for platelet support, the values of the CI, PI and %REC, which best corresponded to 1- and 20 h post-transfusion counts of 20 x 10(9)/l, were identified. A 1-h post transfusion CI < 3 (PI < 7 x 10(9)/l or % REC < 8%) corresponded to clinically unsuccessful transfusions with a 1-h platelet count < 20 x 10(9)/l. A 1-h CI > or = 5.5 (PI > or = 12 x 10(9)/l or %REC > or = 14%) corresponded to clinically successful transfusions with a 20-h post-transfusion count of > or = 20 x 10/l. These data tie together the end points reported in the literature for defining refractory transfusions. PMID- 1308462 TI - Decreasing transfusion exposure risk during extracorporeal membrane oxygenation (ECMO). AB - Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy for neonatal pulmonary hypertension but carries a significant risk for transfusion-related complications. Packed red blood cell (PRBC) and platelet exposure were quantified and reviewed in 17 ECMO survivors prior (Group I, n = 9) and subsequent to (Group II, n = 8) changes in transfusion protocols. Blood product requirements included ECMO circuit priming, maintenance of haematocrit > 0.40 or platelet count > 50 x 10(9)/l, and colloid volume expansion. Group I was exposed to 13.8 +/- 10.2 (x +/ SD) different PRBC units. In Group II, multiple transfusions from single donor units decreased exposure 71% to 3.9 +/- 0.7 units (P < 0.05). Decreases in blood withdrawn (11%) and transfusion volume (7%) were coincident with a 15% reduction in mean bypass time. Platelet volume transfusion decreased from 159 +/- 213 to 93 +/- 64 ml using volume-reduced platelet packs. Total transfusion exposure decreased 59% from 20.8 +/- 17.8 units to 8.6 +/- 2.4 donor units. No transfusion complications occurred during the aggregate 1,926 h on bypass. We conclude that neonates on ECMO have a significant transfusion exposure risk increasing with prolonged duration of ECMO therapy. In addition we noted that concentrated platelet packs decreased transfusion volume by 41%, and multiple PRBC transfusions from single donor units decreased donor exposure by 71% while both strategies decreased the overall transfusion exposure risk by 59%. PMID- 1308463 TI - Transmission of HIV by transfusion of HIV-screened blood: the value of a national register. The 'Recipients' Study Group of the French Society of Blood Transfusion. AB - A National Register of transfusion-transmitted infections was opened by the French Society of Blood Transfusion on 1 October, 1986. Out of 54 initially reported cases of HIV-infection, allegedly transmitted by blood components, further investigation could be completed in 33 cases. The transfusional origin of contamination was considered as established or probable in 28/33 cases, either because a potentially infectious unit was identified among those transfused to the recipient (23/28), or because the recipient was known to be seronegative before transfusion (5/28), or both (10/28). In 5/33 cases transfusion was considered as presumably responsible for contamination because no other risk factor was found in the recipient. Among the 33 documented cases of HIV transmission by screened blood, 29 (88%) occurred between 1985 and 1987, and four (12%) during 1988. Out of 19 implicated donors later found seropositive, 16 belonged to a high-risk group for HIV-infection. The majority of HIV-infections occurred as a consequence of blood donation in the window period between contamination and the appearance of detectable antibodies in the donor's serum (11/19). In three instances, however, human and operational errors led to the release of seropositive units. We conclude that the main value of this Register is to provide a potential trend-indicator of transfusion-related infectious risks, to allow objective documentation of reported cases and to contribute to the improvement of blood transfusion practice. PMID- 1308464 TI - Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force. AB - Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states. PMID- 1308465 TI - Fire works: enlightened management. PMID- 1308466 TI - Nursing informatics in clinical practice: transforming the paper chase. PMID- 1308467 TI - Group facilitation: building that winning team. AB - Team building does not occur by chance; it involves using techniques to make it easier for members to contribute their expertise while working with others to achieve quality results. Evaluation of team effectiveness involves assessing both the processes (team interactions and work processes) and accomplishment of goals (out-comes; see box). Productivity and quality that could not be accomplished by individual efforts may be enhanced by effectively working teams. PMID- 1308468 TI - In vitro and in vivo antidermatophytic activity of saperconazole, a new fluorinated triazole. AB - The in vitro activity of saperconazole against selected isolates of dermatophytes and its in vivo efficacy in a guinea pig dermatophytic infection model using Trichophyton mentagrophytes were evaluated. Susceptibility testing was determined with an agar dilution method in three media: yeast nitrogen base agar (YNBA), brain heart infusion agar (BHIA) and Sabouraud dextrose agar (SDA). An inoculum of 1 x 10(5) CFU of T. mentagrophytes spores was placed onto the surface of these agars. Incubation was at 32 degrees C for 72 h. The MIC of saperconazole against all isolates was less than 1 microgram/ml, whereas the MIC ranged from 0.1 to > 128 micrograms/ml for fluconazole. The MIC range of saperconazole against Trichophyton species was < or = 0.002 to 0.25 micrograms/ml; against Microsporum species it was < 0.001 to 0.1 microgram/ml; and against Epidemophyton species was < or = 0.002 to 0.25 micrograms/ml. These data showed that saperconazole was the most active compound tested against these selected dermatophytes. The activities of saperconazole against T. mentagrophytes, T. rubrum and M. canis were not affected by the medium. The MICs against these organisms were < or = 0.008 micrograms/ml in SDA, YNBA or BHIA. There were 2- to 4-fold decreases in activity for fluconazole at the same conditions. In vivo, topical treatment with saperconazole at concentrations of 0.125% and 0.25% resulted in 50% and 75% microbiological cure rates, respectively, in the guinea pig topically infected with T. mentagrophytes. PMID- 1308469 TI - Effects of a novel piperazine derivative (CGP 29030A) on nociceptive dorsal horn neurons in the rat. AB - In anaesthetized rats and cats, the effects of the piperazine derivative CGP 29030A on the discharges of functionally identified dorsal horn neurons and gamma motoneurons was studied. The compound exhibited a marked inhibitory action on presumably nociceptive dorsal horn neurons that processed input from high threshold mechanosensitive receptors in the skin and deep somatic tissues (muscle, tendon, joint). Significant effects were obtained at a dose of 10 mg/kg p.o. and higher; the onset of action was fast (approximately 10 min). In contrast to presumably nociceptive dorsal horn neurons, cells having input from low threshold mechanosensitive receptors in the skin and deep tissues were not affected by the compound. Thus CGP 29030A has a quite specific action on dorsal horn neurons that probably mediate pain. Systemic effects on the blood pressure and on the activity of sympathetic efferent fibres did not occur. The lack of effect of CGP 29030A on nociceptive neurons in spinalized animals suggests that the site of action is not the segmental spinal cord but the supraspinal CNS. gamma-motoneurons supplying the gastrocnemius-soleus muscle were likewise inhibited by the compound but at a higher dose (equal to and exceeding 30 mg/kg). The data show that CGP 29030A is a compound with marked and specific analgesic action. As it also inhibits gamma-motoneurons, CGP 29030A may be of benefit in the treatment of painful disorders which are complicated by increased motor activity (cramp, spasm). PMID- 1308470 TI - Perinatal exposure to ethanol affects postnatal degeneration and regeneration of serotoninergic pathways in the spinal cord. AB - It has been reported that chronic ethanol exposure during intrauterine life may cause severe adverse effects in early infancy that have been termed fetal alcohol syndrome. These alterations may perturb the normal brain development as though alcohol exposure might have altered the basic cellular interrelationship underlying neuronal plasticity. The neonatal lesion of the serotoninergic pathways in the central nervous system with the selective neurotoxin 5,7-DHT supplies an ideal model for studying the effects of substances of abuse on degenerative and regenerative events. The authors' data indicate that perinatal exposure to ethanol (3% in drinking water) causes a more rapid degeneration of the serotoninergic pathways affected by 5,7-DHT; conversely, regeneration and reinnervation of the lumbar spinal cord are markedly improved by ethanol exposure. These results suggest that perinatal ethanol exposure promotes cellular changes that at later stages are capable of improving neural repair in the brain. PMID- 1308471 TI - Influence of sodium valproate and carbamazepine on GSH levels in rat cerebral cortex. AB - The effects of sodium valproate (150 mg/kg) and carbamazepine (300 mg/kg), alone and in combination, on the content of glutathione (GSH) were investigated in the rat cerebral cortex. No modification was found either 4, 12 or 16 hours after treatment, suggesting that sodium valproate and carbamazepine do not affect the cortical GSH metabolism in rats. PMID- 1308472 TI - Etofibrate treatment alters low density lipoprotein susceptibility to lipid peroxidation. AB - The effect of the lipid lowering drug etofibrate was investigated on lipid peroxidation as well as on cholesterol level. Rabbits were given a 0.1% cholesterol containing diet. Total cholesterol, LDL-cholesterol, triglycerides and lipid peroxidation, expressed as thiobarbituric acid reactive products, were determined. Treatment with etofibrate led to a marked decrease in total cholesterol and LDL-cholesterol. Furthermore, Cu(2+)-induced lipid peroxide formation was reduced in etofibrate treated rabbits. These results could be confirmed in a human study when patients with moderate hypercholesterolaemia were treated with etofibrate (2 x 500 mg/day) for a period of eight weeks. It could be shown that the onset of lipid peroxidation was remarkably increased, an effect which was completely reversible. Thus, etofibrate is effective not only in lowering plasma cholesterol but also in rendering LDL less susceptible to oxidation. PMID- 1308473 TI - Protection of isolated perfused working rat heart from oxidative stress by exogenous L-propionyl carnitine. AB - The effect of exogenous L-propionyl carnitine on peroxidative injury was investigated on isolated working rat hearts. The addition of 190 microM hydrogen peroxide to the perfusion buffer caused a marked decrease in aortic flow, minute work and peak aortic pressure, and a release of intracellular enzymes. In the presence of L-propionyl carnitine the haemodynamic damage was significantly lower and enzyme leakage remarkably decreased. The protection was concentration dependent and the whole structure of the molecule was required, since carnitine alone was found less effective and propionate had no effect. In the absence of hydrogen peroxide L-propionyl carnitine increased heart performance. The effect of L-propionyl carnitine on oxidative stress could account for the beneficial effect of this substance in different models of ischaemic injury. L-propionyl carnitine increases the cardiac performance and protects the rat heart from peroxidation through metabolic and antiperoxidative mechanisms. PMID- 1308474 TI - Pharmacological properties and toxicology of MED-15, a prodrug of tolmetin. AB - In this study the pharmacological evaluation of MED-15, a non-acidic prodrug of tolmetin, is described. After oral administration the new compound shows a marked anti-inflammatory activity similar to that of tolmetin, but with minor ulcerogenic action and lower acute toxicity. PMID- 1308475 TI - Effects of ketoprofen (NSAID) on the pharmacokinetics of pefloxacin and ofloxacin in healthy volunteers. AB - The influence of ketoprofen (K), a non steroidal antiinflammatory drug (NSAID) on the pharmacokinetics of two fluoroquinolone derivatives: ofloxacin (O) and pefloxacin (P) was studied in ten healthy adult male volunteers. All subjects orally received every 12 h the fluoroquinolone derivative (either O or P) for three days and the combination of the quinolone and ketoprofen (once a day) during the three following days. Two pharmacokinetic studies were performed for each quinolone, on days four and eight of the treatment. Blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after dosing. Urine was collected during 4 time-periods: 0-4 h, 4-8 h, 8-12 h and 12-24 h. Plasma and urine concentrations of the active drug of O and P were measured by microbiological assay. Ketoprofen did not significantly modify the pharmacokinetic parameters of the two fluoroquinolones studied in terms of peak plasma levels, time to peak, area under the curve, elimination half-life, volume of distribution and total and renal clearances. PMID- 1308476 TI - Glutathione (GSH) improved haemostatic and haemorheological parameters in atherosclerotic subjects. AB - Blood samples from ten patients with clinically evident manifestations of atherosclerotic disease were used to evaluate in vitro the effects of exogenous glutathione (GSH) on platelet aggregation and on blood filtration and viscosity. In two groups, each of ten atherosclerotic patients, matched for sex, age, prevalent localization, duration and gravity of disease, the effects of GSH infusion (600 mg every day for seven days) on the haemocoagulative pattern, platelet aggregation and blood filtration and viscosity were evaluated in a double-blind, placebo cross-over trial. The GSH in vitro addition resulted in a significant increase in blood filtration and a significant decrease in blood viscosity and platelet aggregation. The venous GSH infusion both significantly decreased blood viscosity and increased blood filtration. Partial thromboplastin time was lengthened after GSH infusion even thought it remained in the normal range. PMID- 1308477 TI - Suppressive effect of prostaglandin E1, but not prostacyclin, on ouabain-induced ventricular fibrillation in guinea-pigs. AB - Arrhythmia was produced by the rapid intravenous injection of ouabain 200 micrograms/kg in anesthetized guinea-pigs. The incidence of ventricular fibrillation (V.F.) induced by the ouabain challenge was significantly decreased by the pretreatment with prostaglandin (PG) E1 5 micrograms/kg or propranolol 0.5 mg/kg, but not with prostacyclin (PGI2) 0.5 or 5 micrograms/kg. Also, a significant number of animals treated with PGE1 or propranolol, but not PGI2, showed recurrent reversion to sinus or ventricular rhythm from V.F. and survived more than 20 min after the ouabain challenge. On the other hand, almost all animals treated with PGI2 produced V.F., which converted to cardiac arrest within 20 min after the ouabain challenge. The finding shows that PGI2 has no protective action on V.F. induced by ouabain in anesthetized guinea-pigs. Involvement of norepinephrine released from sympathetic nerve terminals in ouabain-induced V.F. was assumed. PMID- 1308478 TI - Helical volume CT and its clinical significance. AB - Helical Volume CT (HVCT) is an X-ray CT scanning technique in which the patient is scanned continuously while the couch-top is moved in the axial direction. It is performed using the Toshiba TCT-900S CT scanner jointly developed by the authors and Toshiba Corporation. This scanner features a large central opening, the inner surface of which is lined with a circular array of 2,304 detectors. The X-ray tube rotates outside the detector array at the rate of one revolution per second. Electrical power is supplied to the X-ray tube through a slip ring mechanism, permitting the X-ray to be continuously generated without any interscan delay. The X-ray tube and detectors move in a "nutate/rotate" pattern. The maximum scanning time is 30 seconds (equivalent to a single breath-hold). To improve image quality, the slice thickness can be selected to equal the distance over which the couch-top moves in one second. The clinical advantages of HVCT are as follows: (1) the examination time is significantly reduced (to minimize the patient's discomfort), (2) continuous data of anatomical structures can be obtained without artifacts due to respiratory motion, and (3) it is possible to obtain superior images for multiplanar reconstruction (MPR), cine-display, and three-dimensional reconstruction. PMID- 1308479 TI - The relationship between organ perfusion pressure and multiple organ failure during mechanical left ventricular assist. AB - The purpose of this study was to analyze the relationship between hemodynamics, especially the organ perfusion pressure (OPP = mean aortic pressure-mean right atrial pressure) and multiple organ failure (MOF) in cardiac patients receiving left ventricular mechanical assists (LVA). The subjects were 33 patients who had undergone left ventricular mechanical assists in the Department of Cardiovascular Surgery, Fukushima Medical College Hospital, from March 1985 through March 1990. OPP significantly correlated with the levels of GOT, total-bililubin (TB), BUN and serum-creatinin (s-Cr), oxygenation index (OI) and respiratory index (RI). The cardiac index and left and right ventricular stroke work indices, in comparison with OPP, did not significantly correlate with any of the above laboratory tests. These results indicate that OPP is a simple and reliable index to recognize, and also to prevent MOF during LVA. It was also found that OPP should be maintained at a level higher than 65mmHg to protect the liver, kidneys and lungs. PMID- 1308480 TI - Recording the bladder electromyogram for bladder activity evaluation during post operative urinary urgency. AB - When the intravesical pressure cannot be measured because of continuous drainage, bladder electromyography is an alternative means of evaluating the functional condition of the urinary bladder. However, many problems that accompany this procedure have not been solved. In the present study we tried bladder electromyography with a newly-developed carbon fiber electrode in a patient who underwent an open prostatectomy. It was helpful in recognizing the relationship between urinary urgency and the spasmic activity of the vesicular detrusor muscle. PMID- 1308481 TI - Bronchoscopy for airway foreign bodies: consideration based on an extraordinarily large one. AB - An extraordinarily large foreign body was lodged in the trachea of a 14-year-old boy. It was a rectangular piece of lead measuring 35 x 12 x 5 mm and was removed by a lower rigid bronchoscope introduced through a tracheostoma. Based on experiences of this and 6 other cases of tracheobronchial foreign body treated by this method, we discuss what approach should be used to extract tracheobronchial foreign bodies. We believe that lower bronchoscopy is still useful in removing foreign bodies very large or located in the peripheral bronchus, although it is used much less often today than before. PMID- 1308482 TI - Evaluation of BACTEC 460 TB system for measurement of in vitro anti-Mycobacterium leprae activity of various antimicrobials. AB - In vitro anti-leprosy activities of various antimicrobials were measured by using the BACTEC 460 TB System. The Growth Index reducing activities of test drugs were strong in clofazimine, KRM-1648, rifabutin, clarithromycin and rifampicin; intermediate in sparfloxacin, minocycline and ofloxacin; and weak in ciprofloxacin, fleroxacin and DDS. Amikacin, pipemidic acid, enoxacin and norfloxacin had no such in vitro activities. There is a close correlation between in vitro and in vivo anti-M. leprae activities of a given agent, therefore indicating usefulness of the BACTEC 460 TB System in evaluation of in vitro anti M. leprae activity of a given agent. PMID- 1308483 TI - Demonstration of PGL-I & LAM-B antigens in paraffin sections of leprosy skin lesions. AB - An investigation on the demonstration of PGL-I and LAM-B antigens in thirty-four paraffin embedded skin biopsies taken from leprosy patients who covered the whole spectrum of the disease and in four control specimens was carried out. Neither the PGL-I antigen nor the LAM-B antigen was demonstrated in the normal skin specimens that were used as negative control; and only the LAM-B antigen appeared in the tuberculosis specimens in which the PGL-I antigen was negative. The PGL-I antigen was demonstrated on thirty-three leprosy samples except one TT sample and the LAM-B antigen, on all samples by immunochemical staining technique. The antigens were identified as intracytoplasmic bacillary staining, in solitary, granular as well as debris patterns; and as soluble antigenic staining, in vacuolar or amorphous pattern. In LL and BL cases, the antigens were detected predominantly from macrophages and peripheral nerves in all five staining patterns; in BB cases, from macrophages mostly in the granular as well as debris patterns, from the nerves in the vacuolar pattern; while in TT and the majority of BT cases, they were mainly from nerve remnants inside the granuloma in the vacuolar or amorphous staining pattern. In addition, it is interesting to note that the immunochemical staining was able to differentiate the foamy change from the hydropic degeneration. We also found that the antigens distributed in arrector pili muscles and the walls of muscular vessels were obviously related to the unmyelinated nerve fibers innervating the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308484 TI - [Minobu Jinkyo-En under the influence of Nichiren Sect]. AB - Minobu Jinkyo Hospital was established in 1906 by Ryumyo Tsunawaki, who is a Bonze of Nichiren Sect in Minobu Jinkyo-En Leprosy Foundation, in order to extend a hand of assistance to the Hansenites. The characteristic of this hospital was to reduce the tenets of Nichiren to practice with the fervour of Buddhist. In the heart of people, either volunteer staffs or Hansenites, flocked here from various quarters, was fostered the spirit of self-restraint and/or -government under the influence of the Buddhist Sutra. The daily life of Hansenites in Jinkyo Hospital has veered round according as it is said that man is a creature of circumstances. Things are not what they used to be. And, Jinkyo-En which was a desolate waste has come to an oasis in life for the Hansenites. A small and decreasing number of inpatients are found annually and rehabilitation of cured patients back into society has been made possible, now. High aim of Bonze Tsunawaki was to establish rightful place for Hansenites, and it was fulfilled. Minobu Jinkyo Hospital was closed in 1992. PMID- 1308485 TI - AIDS-the Indian scene. PMID- 1308486 TI - Signal averaged ECG and late potentials. PMID- 1308487 TI - Pre-Addisonian state: does it exist? PMID- 1308488 TI - Rising trend of HIV infection with special reference to blood donors. AB - This paper describes the experience in testing for antibodies to the human immunodeficiency virus (anti-HIV) at a private institution. A total of 31,003 persons were tested between August 1986 and June 1990 including 20, 321 blood donors. The other 10,712 were visitors to the Ohso International Commune (OIC), a commune for followers of Osho Rajneesh. Another 133 patients, 45 of whom had been repeatedly transfused, were also tested. Thirty two persons tested positive-22 blood donors, 4 visitors to OIC and 6 patients. The seropositivity of unselected blood donors was O of 273 donors in 1986, 1 of 2836 in 1987 (0.04%), 2 of 5373 in 1988 (0.04%), 11 of 7201 in 1989 (0.15%) and 8 of 4640 in the first half of 1990 (0.17%). Since non-professional blood donors represent a sample of the general population, a rise in seropositivity in the former may imply a rise in the latter. PMID- 1308489 TI - Significance of ventricular late potentials in patients with myocardial infarction. AB - Fifty six patients (52 males, 4 females, mean age 53.6 +/- 8 years, range 35-75 years) were studied to determine the influence of clinical variables, site of myocardial infarction, thrombolytic therapy, documented arrhythmias and left ventricular ejection fraction (LVEF) on the incidence of ventricular late potentials (LP's). LP's were detected in 17 (30.3%) patients; in 6 (26%) patients with acute and in 11 (33.3%) patients with old healed myocardial infarction. 87.5% of the patients in whom LPs were detected had low LVEF. The presence of low LVEF correlated significantly with the presence of LP's (p = .02). LP's were also present in all patients with documented sustained ventricular tachycardia. Clinical variables (Killip and NYHA class), site of myocardial infarction, Q wave versus non-Q wave myocardial infarction and thrombolytic therapy did not relate to the presence of LP's (p > 0.5) Patients of myocardial infarction with low LVEF and a history of ventricular tachyarrhythmias should undergo signal averaged electrocardiography for LP detection. LP presence would identify patients at higher risk of future arrhythmic events within this subgroup. PMID- 1308490 TI - Oxygen desaturation and tachycardia during upper gastrointestinal endoscopy are transient and benign. AB - We continuously monitored the arterial oxygen saturation (SaO2) and pulse rate by pulse oximetry in 46 patients undergoing upper gastrointestinal endoscopy for diagnosis (21 cases) or variceal sclerotherapy (25). No premedication or prior topical anaesthesia was used. Significant hypoxaemia (percent drop in SaO2 > 2) occurred in 24 (52%) patients during the procedure; in 16 of these it occurred during introduction of the endoscope. Twenty seven (59%) patients had hypoxaemia during recovery, 25 of these immediately after withdrawal of the endoscope. All these episodes were short-lived and were probably due to gagging; basal levels were reached within 1 to 5 min. Tachycardia (> 100 beats/min) occurred in 41 (89%) patients. Sclerotherapy and history of smoking did not affect the incidence and magnitude of hypoxaemia and tachycardia. Transient cardio-respiratory changes occur during and immediately after endoscopy, but these appear to be clinically benign. PMID- 1308491 TI - Sleep disorders. PMID- 1308492 TI - Recent trends in the diagnosis and treatment of Budd Chiari syndrome. PMID- 1308493 TI - Hypercalcemic encephalopathy in a patient on anti-TB treatment for glandular tuberculosis. AB - An 84 years old male patient presented with hypercalcemic encephalopathy and mild azotemia while on anti-tuberculous treatment for glandular tuberculosis. He recovered fully during treatment with hydration, intravenous frusemide and oral prednisolone while continuing on the antituberculous therapy. PMID- 1308494 TI - Gloriosa superba poisoning. AB - Suicidal attempts by consuming poisonous extracts of a creeper plant Gloriosa superba are frequent in this region. An instance of such poisoning is reported here, wherein a family engaged in business dealing with this plant consumed the crude liquid extract of its root. The symptoms were mainly gastrointestinal. The children had more severe symptoms which included sweating, hypotension, jaundice, bradycardia and convulsions. The features were reversible with symptomatic treatment alone. PMID- 1308495 TI - Type II paralysis or intermediate syndrome following organophosphorous poisoning. AB - Three cases of type II paralysis or intermediate syndrome following organophosphorous poisoning are reported. Two patients had an initial improvement followed by development of paralysis of neck flexors, cranial nerves, proximal muscles of the limbs and respiratory muscles, which occurred 48 to 96 hours after the poisoning. All the patients recovered completely. PMID- 1308496 TI - A comparative study of bronchodilator actions of ipratropium bromide (atrovent) & salbutamol (ventolin) on exercise induced bronchial asthma. AB - The bronchodilator actions of salbutamol and ipratropium bromide were compared in 30 established cases of bronchial asthma, before and after exercise. It was noticed that after exercise (brisk walk for 3 min.) the PFT values of FVC, PEFR and FEV-1, decreased remarkably from the basal values, the mean fall of 17.91%, 10.68% & 14.8% respectively was noticed. Salbutamol showed improvement in FVC, PEFR, FEV-1, of 20.86%, 15.96% & 17.98% respectively from basal values, while Ipratropium bromide showed improvement by 18.31%, 13.01% & 20.90% respectively. It was also noted that salbutamol is a better drug amongst smokers, patients with family history of bronchial asthma, and in younger age groups. Ipratropium bromide was better in elderly patients (> 40 yrs.) and in those with eosinophillia. PMID- 1308497 TI - Rhabdomyolysis and acute renal failure following a single dose of succinylcholine. PMID- 1308498 TI - "Bilateral thalamic hematoma" following snake bite. PMID- 1308500 TI - Prosthetic valve problems. PMID- 1308499 TI - Amoebic liver abscesses presenting with psoas abscess. PMID- 1308501 TI - Thalamic haemorrhage due to tubercular arteritis. PMID- 1308502 TI - Metabolic acidosis in acute renal failure following acute diarrhoeal disease--an important prognostic factor? PMID- 1308503 TI - "Not smoking alone" but tobacco. PMID- 1308504 TI - Limitation of cardiothoracic ratio in chronic obstructive airway disease. PMID- 1308505 TI - Priapism in rabies. PMID- 1308506 TI - Significance of aspergillus precipitin in sarcoidosis. PMID- 1308507 TI - Similar data different interpretations. PMID- 1308508 TI - Anticholinergics in myasthenia gravis. PMID- 1308509 TI - Diabetic autonomic neuropathy and foot ulceration. PMID- 1308510 TI - Inspection of arterial pulses and cerebrovascular disease. PMID- 1308511 TI - Rabies vaccine. PMID- 1308512 TI - Insulin requirement formula. PMID- 1308513 TI - Should haem preparations be banned? PMID- 1308514 TI - Lymphoma. PMID- 1308515 TI - Status epilepticus and death following acute carbamazepine poisoning. PMID- 1308517 TI - Acute pericarditis in aluminium phosphide poisoning. PMID- 1308516 TI - Multidrug resistant enteric fever. PMID- 1308518 TI - Left atrial thrombus with mitral stenosis. PMID- 1308519 TI - Venezuela results and after. PMID- 1308520 TI - Gelatin particle agglutination assay to detect anti-PGL-I antibodies in leprosy patients and in household contacts: a preliminary study. AB - A preliminary study of anti-phenolic glycolipid-I (PGL-I) IgM antibody detection using M. leprae gelatin particle agglutination (MLPA) test kit is described. Antibodies were demonstrated in 70% of our leprosy patients taking antileprosy treatment. The percentage of positivity of multibacillary cases was 86.0, whereas that of paucibacillary cases was 30.0. Good correlation was found between bacteriological index and the presence of antibodies. Antibodies were detected in 28% of our patients released from treatment. Fourteen out of 27 household contacts were found to have antibodies but none of the normal controls were seropositive. These preliminary data demonstrate that MLPA test is not applicable as sero-diagnostic test or as a test of cure, but may be useful for epidemiological studies and as a research tool. PMID- 1308521 TI - Utility of gelatin particle agglutination test (MLPA) for rapid serodiagnosis of leprosy in a hyperendemic area. AB - The anti-PGL M. leprae specific antibodies were estimated by MLPA test in 79 patients of leprosy, 8 contacts of lepromatous cases and 10 healthy controls in a hyperendemic area. The results indicated an over all seropositivity of 50.6% in leprosy patients. Three of the eight contacts and five of the controls also gave positive results. Higher seropositivity rates were noted in multibacillary patients (73% in lepromatous, 53.6% in borderline, 40% each in tuberculoid and indeterminate and 10% in pure neuritic types). The practical application of MLPA test in its present form as a serodiagnostic procedure for screening subclinical or clinical infections in leprosy patients appear to be of limited value in hyperendemic areas. Further studies involving large series of subjects are necessary for reaching definite conclusions. PMID- 1308523 TI - Prevalence of colour blindness among patients with leprosy. AB - Using Ishihara test plates the prevalence of colour blindness was studied on six hundred and ninety-seven leprosy patients and two hundred and ninety-two normal healthy controls. 7.88% of male patients with tuberculoid leprosy, 12.18% of male patients with lepromatous leprosy, and 0.67% of male controls were detected to be colour blind (red-green deficiency or total colour weakness). The differences between the different groups are significant. Among female patients and controls, only one lepromatous leprosy patient was detected to have red-green deficiency. This suggests the possibility of a genetic predisposition to Mycobacterium leprae infection in patients with leprosy. PMID- 1308522 TI - Utility of beige mouse in leprosy research. AB - Dissemination of M. leprae to visceral organs is seen by four months onwards only in beige (C57BL/6/bgj) but not BALB/c mice following intravenous or intraperitoneal infections. Inoculation of the beige mouse derived M. leprae showed all the characteristics of M. leprae, including growth pattern in the foot pads of BALB/c mice. M. leprae inoculated into foot-pads of beige mice multiplied faster than those in the foot-pads of BALB/c mice. The possibility of using beige mouse in chemotherapeutic studies in leprosy is discussed. PMID- 1308524 TI - A clinical and radiological study of maxillary antrum in lepromatous leprosy. AB - Seventy consecutive patients having multibacillary leprosy were questioned about symptoms of nasal involvement and sinusitis. Complete otorhinolaryngeal examination was carried out in all these patients and they were subjected to radiographic examination of paranasal sinuses. Radiological abnormality of maxillary antrum was found in 40 (57%) patients. Radiological changes were unilateral in 25 and bilateral in 15 patients. Localised or generalised mucosal thickening was the most common finding, followed by diffuse opacity. The development of radiological changes in maxillary antrum correlated with high bacterial density (BI 3+ and above), nasal deformity, and disease duration of more than two years. PMID- 1308525 TI - Induction of lepromin positivity by a candidate anti-leprosy vaccine Mycobacterium w in lepromin negative healthy contacts of multibacillary leprosy patients. AB - In a hospital based study, 362 household contacts of multibacillary leprosy patients were screened for evidence of leprosy and 54 (14.9%) were found to be having leprosy. The remaining 308 apparently healthy contacts were lepromin tested and 109 (35.4%) were observed to be negative to Mitsuda lepromin. M.w vaccine was administered intradermally to 95 of these 109 lepromin negative contacts. Sixty eight of them could be retested for lepromin A reactivity. Fifty six (82.35%) manifested lepromin conversion. The twelve subjects who did not show lepromin conversion, received a second dose of the vaccine, and eleven subsequently became lepromin positive. The overall lepromin conversion rate was thus 98.5% (67 out of 68). Follow-up of these contacts upto a period of 30 months did not demonstrate reversion of lepromin positivity back to negativity status. No untoward effects of vaccination were observed except for local ulceration at the site of vaccine administration. PMID- 1308526 TI - Comparison of two multidrug regimens in multibacillary leprosy. AB - One of the technical problems relating to the multidrug therapy of leprosy is the slow decrease in the bacteriological index (BI) in multibacillary patients. In this study we have compared a regimen containing rifampicin given daily for 9 months with the standard WHO multidrug regimen for multibacillary leprosy. We have found, at the end of two years, a significantly greater fall of BI in patients who had received the regimen containing daily rifampicin as compared to those who had received pulsed doses of rifampicin. The doses of dapsone and clofazimine were similar in these two groups. It appears that daily administration of rifampicin may be useful in treating multibacillary patients in whom reduction in the BI is slower than expected. However, in view of its high cost and the very much increased incidence of type-2 lepra reactions and hepatitis, daily rifampicin therapy cannot be recommended for a control programme. PMID- 1308527 TI - Variables influencing regularity of leprosy patients in attending treatment clinics. AB - Regularity in attending clinics as well as taking drugs assume a very significant place in leprosy control programme since irregularity of leprosy patients can lead to poor disease control, drug resistant disease, and development of physical deformities and disabilities thus leading to programme failure. Further, these complications also create socio-economic and psychological problems to the victims as well as their families in myriad ways. This paper reports a study aimed at identifying the variables, among a set of 29 selected demographic, socio economic and disease-related variables, having significant association with regularity of leprosy patients in attending treatment clinics. It was found that age of the patients, type of family, duration of the disease, time lag between diagnosis of the disease and starting treatment and knowledge of patients and their families about the disease were significantly associated with treatment regularity. PMID- 1308528 TI - Estimated number of leprosy cases in the world. AB - Planning for disease control requires estimates of the number of leprosy patients from local to global levels. From the mid-sixties to the mid-eighties, global estimates appeared to be constant at between 10 and 12 million. The introduction of multidrug therapy (MDT) in many countries and the consequent reduction of prevalence of the disease has necessitated a reassessment of the global estimate. Based on available information and its interpretation, the number of leprosy cases in the world in 1991 has been estimated at 5.5 million. The number of individuals with deformities due to leprosy, including persons now cured of the disease, has been estimated at between two and three million. PMID- 1308529 TI - Leprosy-derived chemoautotrophic nocardioform (CAN) bacteria closely resemble, or are identical with, Mycobacterium leprae on mycolate and other lipid profiles. AB - On the basis of thin layer chromatography and gas-chromatography-mass spectrometric studies, the lipid profiles of all the chemoautotrophic nocardioform (CAN) bacteria derived from human and animal leprosy tissues appear to be identical with each other, and closest to or identical with the most probable profile of M. leprae. PMID- 1308530 TI - Rifampicin induced flu-syndrome and toxic psychosis. PMID- 1308531 TI - Involvement of scalp, axillae and groins in lepromatous leprosy. PMID- 1308532 TI - Diagnosis of leprosy by senior persons. PMID- 1308534 TI - Paucibacillary multidrug therapy in leprosy--7.5 years experience. PMID- 1308533 TI - BCG vaccination and leprosy. PMID- 1308535 TI - Corticosteroid treatment of extensive hemangiomas: analysis of 22 cases in children. AB - During the past 16 years, 22 Thai infants with extensive hemangiomas which impaired bodily functions and were life-threatening, especially in Kasabach Merrit Syndrome have been treated. The incidence of female-to-male ratio was 8:3, all of the hemangiomas appeared between birth and 3 months of age. Among the 22 infants, 11 (50%) had hemangiomas on the head and the neck, and 2 had laryngeal hemangiomas. Two cases of Kasabach-Merrit Syndrome, located at the shoulder and the thigh, were complicated with severe bleeding, infection and congestive heart failure. Ocular impairment, malocclusion, and cutaneous distortion were the most important functional problems. Three cases were associated with other congenital anomalies: intracranial angioma, Dandy Walker Syndrome and Klippel-Trenauncy Syndrome. Prednisone (2-4 mg/kg/d) was used in all cases with other symptomatic treatment. Antiplatelet aggregating and antithrombotic drugs were useful in Kasabach-Merrit Syndrome. Definite response was noted in 72.72 per cent of the patients, doubtful response in 23.32 per cent, and no response in 4.54 per cent which was better than in other reports. There were no serious side-effects of the corticosteroid treatments reported in our careful students. PMID- 1308536 TI - Antimicrobial resistance of 100 serial gram-negative isolates in two intensive care units. AB - To determine antimicrobial resistance pattern among gram-negative bacteria isolated from suspected sources of infections in patients hospitalized in two Intensive Care Units (ICUs) at Siriraj Hospital from September 1991 to December 1991, minimal inhibitory concentrations of one-hundred consecutive gram-negative isolates for various antimicrobials were performed using the microbroth dilution method. Of all gram-negative bacterial isolates, 25 per cent were Pseudomonas aeruginosa, 22 per cent Acinetobacter anitratus, 16 per cent Klebsiella pneumoniae, 12 per cent enterobacter, 8 per cent E.coli, 5 per cent non fermenter, 4 per cent pseudomonas, 3 per cent arizona, 2 per cent A. lwoffii, 1 per cent Aeromonas hydrophila, 1 per cent Aeromonas hydrophila, 1 per cent Proteus rettgeri, and 1 per cent shigella. The in vitro MIC study revealed that 50, 48, 43, 61, 59, 34, 47, 52, 31, 15 per cent of gram-negative isolates were resistant to gentamicin, tobramycin, amikacin, cefotaxime, ceftriaxone, ceftazidime, aztreonam, piperacillin, ciprofloxacin and imipenem respectively. In addition, 64 and 71 per cent of the isolates were resistant to aminoglycosides and cephalosporins being used in the same patients 48 hours before cultures were obtained respectively. The possible spread of resistant gram-negative isolates by cross contamination was not evident by looking at MIC co-variation in sequential isolates of P. aeruginosa. It was concluded that antimicrobial resistance was highly prevalent among gram-negative bacteria isolated from patients already hospitalized in the ICUs. Potent antimicrobials such as imipenem, newer fluoro quinolones, ceftazidime and amikacin, are often needed for therapy of serious gram-negative bacterial infections in the ICUs. PMID- 1308537 TI - Pancreas divisum: incidence and clinical evaluation in Thai patients. AB - Five hundred patients with successful pancreatogram between 1982 and 1990, 8 patients (1.6%) were found to have complete pancreas divisum. The sex distribution was equal (4 men, 4 women), and the average age was 42.5 years (22 77 years). No increased incidence of pancreas divisum in any of the three groups: a group with pancreatitis, a group with unexplained upper abdominal pain, and an incidental group (obstructive jaundice, gall bladder disease, abdominal mass, miscellaneous). These findings show that pancreas divisum is a normal anatomic variant with an incidence of 1.6 per cent in Thai patients, and is seldom a cause of pancreatic symptoms. PMID- 1308538 TI - Symptomatology and hormonal levels among Thai women with natural menopause. AB - The hormonal levels and symptoms after natural menopause have been studied in 100 patients. The mean age was 56.8 years while menopausal age was 50.3 years. Postmenopausal symptoms presented 55.0 per cent with the three most common complaints of hot flushes, emotional lability and vaginal dryness, respectively. The levels of plasma FSH, estradiol and testosterone were also reported corresponding to the years after menopause. Both gonadotropins reach a maximum concentration at two to three years after the menopause and then gradually declined. The LH/FSH ratio was 0.6. The mean concentration of estradiol was 10.07 pg/ml, the level remained consistently low during the menopausal period. Testosterone concentration declined little in postmenopausal women. PMID- 1308539 TI - The effects of medial patellar plica on clinical diagnosis of medial meniscal lesion. AB - A prospective study involving 190 patients presenting with symptoms suggesting internal derangements of the knee was performed to demonstrate the likelihood of symptoms and signs produced by medial patellar plica to mimic those of medial meniscal lesions. Arthroscopic examination was done in each patient by an independent examiner after the establishment of clinical diagnoses. Only patients with isolated medial patellar plica (Group A, n = 54) and isolated medial meniscal lesion (Group B, n = 19) were further assessed. Although isolated medial patellar plica can produce symptoms and signs similar to medial meniscal lesion, statistical analysis clearly demonstrated that giving way, locking, medial joint line tenderness and positive McMurray test were more commonly detected in Group B (p < 0.05). The sensitivity of detecting either one or more than one symptom or sign included in this study was higher in group B (89.5%), but a positive symptom or sign was more predictive in Group A (39.2%). Considering the variation of prevalence of medial patellar plica in other regions, the results from this study indicate that giving way, locking, clicking, medial joint line tenderness and positive McMurray test would be more predictive of medial patellar plica and thus clinical diagnosis of medial meniscal lesion might be affected if the prevalence of isolated medial patellar plica exceeded 16.6 per cent. PMID- 1308540 TI - Serum lipid, lipoprotein-cholesterol and apolipoproteins A-I and B of smoking and non-smoking males. AB - Cigarette smoking is an important risk factor for coronary heart disease, stroke and peripheral vascular disease. Accordingly, we measured the serum lipid, lipoprotein-cholesterol and apolipoprotein A-I, B in 128 cigarette smoking males and 67 non-smoking males. The total cholesterol and LDL-cholesterol in smokers and non-smokers showed no statistical significance. The smokers had significantly higher serum triglyceride and VLDL-cholesterol levels (P < 0.001), but significantly lower HDL-cholesterol levels (P < 0.05) than non-smokers. The apolipoprotein A-I was significantly lower and apolipoprotein B was significantly higher in smokers than non-smokers (P < 0.001). Levels of lipid, lipoprotein cholesterol were related to the number of cigarettes smoked per day. Triglyceride and VLDL-cholesterol levels were significantly higher in those who smoked > 20 cigarettes/day compared with those who smoked 10-20, < 10 cigarettes/day and non smokers (P < 0.05). Those who smoked > 20 cigarettes/day had significantly lower HDL-cholesterol than those of non-smokers (P < 0.05). All three groups of smokers had significantly lower apolipoprotein A-I than non-smokers (P < 0.05), whereas, those who smoked > 20 cigarettes/day had significantly higher apolipoprotein B levels than those who smoked 10-20, < 10 cigarettes/day and non-smokers (P < 0.05). PMID- 1308541 TI - Optic neuropathy in a patient with vitamin B12 deficiency: a case report. AB - A 19-year-old man presented with blurring of vision for 2 weeks. He also complained of anorexia with weight loss during the past 4 months. Eight years ago, his small bowel from midportion of the jejunum, ileum, ascending colon and transverse colon were resected because of gangrene. He gave no history of exposure to tobacco, alcohol or other toxins. The bone marrow aspiration showed hypocellular with panhypoplasia. Serum vitamin B12 level was low while serum and red cell folate were within normal limits. His visual acuity was 5/200 in both eyes with centrocecal scotomas in both eyes. Other neurologic and ophthalmic examinations were found to be normal. The patient was given intramuscular injections of 1,000 micrograms of cyanocobalamin. Four months later, his visual acuity improved, serum vitamin B12 level and the bone marrow returned to be normal. This is a frank case of optic neuropathy in a patient with vitamin B12 deficiency due to a massive small bowel resection. PMID- 1308542 TI - Urinoma, a case report with unusual presentation. AB - A case of urinoma in a 28-year-old man who had received blunt abdominal injury was reported. This urinoma developed from the detached but still functioned upper pole of the right kidney. The misdiagnosis from the previous surgical exploration and subsequent investigations thus delayed the proper management. PMID- 1308543 TI - Brazilian dengue virus type 1 replication in mosquito cell cultures. AB - The development of dengue viruses type 1 obtained from acute human sera and inoculated into mosquito cell cultures, was observed by standard transmission electron microscopy and cytochemical staining. It follows the trans-type mechanism already established of other dengue types. Direct passage of single virus particles across the cell membrane seems to be a pathway of entry and exit in dengue-1 infected cells. The nature of numerous electron translucent vesicles and tubules, produced simultaneously during virus replication inside the rough endoplasmic reticulum, was analyzed by cytochemical tests. The largest amount of virus particles was produced inside cell syncytia. PMID- 1308545 TI - Influence of temperature on survival, growth and fecundity of the freshwater snail Indoplanorbis exustus (Deshayes). AB - To note the effect of temperature on survival, growth and fecundity, newly hatched (zero day old) snails Indoplanorbis exustus were cultured at 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees and 35 degrees C constant temperatures and room temperature (17.5 degrees-32.5 degrees C). Individuals exposed to 10 degrees C died within 3 days while those reared at 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees C and room temperature survived for a period of 6, 27, 18, 16, 12 and 17 weeks respectively. An individual added on an average 0.21 mm and 0.45 mg, 0.35 mm and 7.94 mg, 0.63 mm and 15.5 mg, 0.81 mm and 27.18 mg, 1.07 mm and 41.48 mg and 0.78 mm and 31.2 mg to the shell diameter and body weight respectively at those temperatures per week. The snails cultured at 15 degrees C died prior to attainment of sexual maturity. On an average, an individual produced 31.9 and 582.77, 54.86 and 902.18, 56.01 and 968.45, 49.32 and 798.68 and 62.34 and 1143.97 capsules and eggs respectively at 20 degrees, 25 degrees, 30 degrees, 35 degrees C and room temperature (17.5 degrees-32.5 degrees C). PMID- 1308544 TI - Modeling AIDS vaccines: the cellular level. AB - This paper discusses current strategies for the development of AIDS vaccines which allow immunization to disturb the natural course of HIV at different detailed stages of its life cycle. Mathematical models describing the main biological phenomena (i.e. virus and vaccine induced T4 cell growth; virus and vaccine induced activation of latently infected T4 cells; incremental changes in immune response as infection progresses; antibody dependent enhancement and neutralization of infection) and allowing for different vaccination strategies serve as a background for computer simulations. The mathematical models reproduce updated information on the behavior of immune cells, antibody concentrations and free viruses. The results point to some controversial outcomes of an AIDS vaccine such as an early increase in virus concentration among vaccinated when compared to nonvaccinated individuals. PMID- 1308546 TI - Isolation and characterization of a Plasmodium falciparum strain: comparative study with four described strains. PMID- 1308547 TI - Analytic morphometry of the Trypanosoma cruzi (Bolivia strain) forms found in the intestine of Rhodnius prolixus. PMID- 1308548 TI - Montenegro skin tests in dogs experimentally infected with Leishmania (Viannia) braziliensis. PMID- 1308549 TI - A preliminary study of vector control with polystyrene beads in Recife, Brazil. PMID- 1308550 TI - Brazilian urease-positive strains of Vibrio parahaemolyticus carry genetic potential to produce the TDH-related hemolysin. PMID- 1308551 TI - Evaluation of the molluscicidal properties of Euphorbia splendens var. hislopii (N. E. B.) (Euphorbiaceae)--1. Experimental test in a lentic habitat. AB - The latex of Euphorbia splendens var. hislopii, at concentrations between 5 to 12 mg/l, kills 100% of the population of Biomphalaria glabrata in a lentic habitat, after 24 h. The lyophilized latex, stocked for 18 months, killed only 34.2% of the snails, at the concentration of 5 mg/l, and 96.0% at 12 mg/l. No lethal effect was observed among Pomacea haustrum exposed to the same concentrations of the molluscicide. PMID- 1308552 TI - Dynamics of fibrosis production and resorption in intestinal schistosomiasis of mice. AB - A histological, morphometric and immunocytochemical study of schistosomal periovular granulomas in the liver and intestines of mice revealed that intestinal granulomas are smaller and contain less collagen than those in the liver. After curative treatment intestinal granulomas undergo a relatively more rapid resorption, although the general pattern of collagen degradation apparently does not differ from that observed in the liver. Tendency to form scattered, usually isolated granulomas that are only mildly fibrogenic, coupled with a well balanced process of resorption appear as the explanation why intestinal fibrosis is not an outstanding feature of schistosomiasis as it is in the liver. PMID- 1308553 TI - Parasites of commercial shrimps and fishes in Argentine sea: on the adult and metacercaria of Opecoeloides feliciae n. sp. (Digenea: Opecoelidae). AB - Opecoeloides feliciae n. sp., first record of opecoelid metacercariae in commercial shrimps of South Atlantic Ocean, parasitizing Cynoscion striatus (adults) and Artemesia longinaris (metacercariae), is described, illustrated and compared with related species of the genus. Adults, immature worms and metacercariae are compared, and rates of prevalence and intensity of infection are also given. PMID- 1308554 TI - Development of Ascaris lumbricoides eggs from females eliminated after chemotherapy in man. AB - The development of Ascaris lumbricoides eggs obtained from females eliminated after treatment of infected individuals with a single oral dose of the antihelminthic drugs thiabendazole (50 mg/kg--33 patients) or levamisole (250 mg- independent of body weight--20 patients) was studied. Every female eliminated up to 72 h after treatment were dissected, the uterus isolated and sectioned into small fragments. The eggs were transferred to plastics tubes and incubated at 28 degrees C in 0.1 N H2SO4 for 100 days. Every 20 days, starting from the 20 th up to the 100 th day, the extent of egg embryonation ratio was determined. The culture of A. lumbricoides eggs obtained from females from patients treated with thiabendazole did not contain embryonated eggs until the final period of observation. In contrast, the eggs obtained from females eliminated by patients treated with levamisole (control) presented an embryonation rate of 0.0-98.0% in the same period. PMID- 1308555 TI - A medium for inducing conversion of Histoplasma capsulatum var. capsulatum into its yeast-like form. AB - Histoplasma capsulatum var. capsulatum is a dimorphic fungus that, under special conditions, converts from its more common mycelial form to a yeast-like form. Achieving this conversion, however, has been problematical for researchers. The present study tested conversion rates in ten Histoplasma capsulatum var. capsulatum strains using seven culture media, four of which were conventional and three novel. One of our novel media, MLGema, induced complete conversion of two strains within five days of incubation at 35 degrees C, and of all strains that eventually converted by the time of the second subculturing transfer, under defined experimental conditions. MLGema is also inexpensive and easy to produce. PMID- 1308556 TI - Experimental Chagas' disease in dogs. AB - This paper describes the development of experimental Chagas' disease in 64 out bred young dogs. Twenty-nine animals were inoculated with the Be-62 and 35 with Be-78 Trypanosoma cruzi strains. Twenty-six were infected with blood trypomastigotes by different inoculation routes and 38 with metacyclic trypomastigotes from the vector via the conjunctival route. Twenty of the 26 dogs infected with blood trypomastigotes were autopsied during the acute phase. Eleven died spontaneously and nine were sacrificed. Six remained alive until they died suddenly (two) or were autopsied. (four). Twelve of the 38 dogs infected with metacyclic trypomastigotes evolved naturally to the chronic phase and remained alive for 24-48 months. The parasitemia, clinical aspects and serology (IgM and IgG) as well as electrocardiogram, hemogram and heart anatomo-histopathologic patterns of acute and chronic cardiac forms of Chagas' disease as seen in human infections, were reproduced. The most important finding is the reproducibility of diffuse fibrosing chronic chagasic cardiopathy in all dogs infected with Be-78 T. cruzi strain autopsied between the 90th and 864th days of infection. Thus, the dog can be considered as a suitable experimental model to study Chagas' disease according to the requisites of the Word Health Organization (1984). Furthermore the animal is easily obtained and easy to handle and maintain in experimental laboratory conditions. PMID- 1308558 TI - Leishmania braziliensis spp. in the nasal mucosa of guinea pigs inoculated in the tarsi. AB - Two lots of 20 young male guinea pigs were inoculated subcutaneously in the tarsi with 10(4) amastigotes of Leishmania braziliensis braziliensis or L. b. guyanensis to study the susceptibility of this Neotropical hystricomorph rodent the autochthonous parasites. Almost 50% of the animals showed lesions in the inoculation site and had parasitizations that were infective to hamsters, as shown by inoculating homogenates of the dermal lesion, of the spleen, of the liver, and of the nasal mucosa into hamsters at 20, 40, 60, and 120 days after inoculation of the guinea pig. Smears of the above organs showed the presence of amastigotes. Parasites inoculated into the tarsi were detected early in the skin, spleen, and liver of the guinea pig host. Blood cultures made by cardiopuncture on sacrifice of the guinea pigs were uniformly negative. The nasal mucosa of nearly all animals positive in the skin or viscera was invaded early by the parasites, although with greater frequency between 60 and 120 days post inoculation. The use of this model for the study of mucocutaneous parasitism by L. braziliensis is discussed, together with the phenomena of parasitism at a distance from the inoculation site, the temperature of the body regions affected, and the possible genetic influence on susceptibility of the guinea pig to L. braziliensis. PMID- 1308557 TI - The epidemiological significance of Chagas' disease in women. AB - Little is known about the risks associated with Trypanosoma cruzi infection in non-pregnant and pregnant women. From a limited number of studies it appears that in rural areas, parasite rates and rates of serological positivity are similar in both sexes. Abnormal ECG tracings are consistently more frequent in men suggesting that immunity to T. cruzi may be different in females. Complications arising from Chagas' disease in pregnancy are only infrequently reported. Evidence for increased risk of abortion or prematurity is inconclusive except in cases of congenital infection. Most cases of congenital Chagas' disease have been reported from non-endemic areas and there is a suggestion that parasitemic episodes during pregnancy may influence pregnancy outcome. Preliminary evidence indicates that chronic infection can result in in-utero sensitization via passively acquired maternal antibodies. The review concludes that maternal T. cruzi infection carries risks for the child and these warrant systematic research because of their public health significance. PMID- 1308559 TI - Evaluation of three serological tests for the detection of human plague in northeast Brazil. AB - The passive haemagglutination (PHA) test, enzyme-linked immunosorbent assay (ELISA) and the dot enzyme-immunosorbent assay (DOT-ELISA) were used to detect the levels of IgG antibodies against the Fraction 1 (F1) antigen of Yersinia pestis in sera of plague-infected patients from Northeast Brazil. Twenty three selected PHA-positive sera of subjects with bacteriological confirmation of plague were also positive in the DOT-ELISA but only 19 were detected by the conventional ELISA technique. Another group of 186 serum samples from subjects diagnosed as plague-infected by clinical and epidemiological parameters, but PHA negative, were screened with DOT-ELISA and 11 gave positive results. The specificity of the assays on the serological detection of plague was confirmed in inhibition tests using purified F1 antigen. These results suggest that DOT-ELISA can be an useful, simple and more sensitive alternative for the serodiagnosis of plague in Northeast Brazil. PMID- 1308560 TI - Catadiscus pomaceae sp. n. (Trematoda, Paramphistomatidae) from Pomacea canaliculata (Lamarck, 1801) (Prosobranchia, Ampullariidae). AB - Catadiscus pomaceae sp. n. from the intestine of the prosobranch mollusc Pomacea canaliculata (Lamarck, 1801), is described. The host snail was collected from a lenitic biotope belonging to the Riachuelo basin (Corrientes province, Argentina) during 1985-1986. So far the species of the genus Catadiscus Cohn, 1904 have been recorded in amphibians and reptiles. This is the first instance of a species of that genus parasitizing a mollusc. PMID- 1308562 TI - Spatial and seasonal trends of a natural population of Biomphalaria occidentalis in northeastern Argentina. AB - This study aims to analyze the age structure of a population of Biomphalaria occidentalis on a pond of Riachuelo river basin, which is one of the three most important Middle Parana river affluents in Corrientes province. Samples were drawn from three stations, where spatial and temporal numerical variations of the snail, as well as its relation with different environmental parameters, mainly temperature, rainfall, pH and conductivity, were analyzed. Snail abundance is given in number of individuals/hour. The differences between the three sampling stations, estimated by nonparametric tests, was nonsignificant. A relative scale to the greatest shell diameter was employed to build the age pyramids. Temporal fluctuations of snail abundance correlated negatively with the highest monthly accumulated temperatures (P < 0.05). Although different floristic compositions were observed at the three stations, no significant numerical variations were detected in B. occidentalis spatial distribution. Reproductive activity took place between March-April and November with overlapping cohort system. During summer (December-February) mortality increased along with temperature and reproductive activity was not evident. PMID- 1308561 TI - Localized, diffuse, and aggregative-adhering Escherichia coli from infants with acute diarrhea and matched-controls. AB - Of 126 infants under 2 years, enrolled in a study on the etiology of acute diarrhea in Recife, Brazil, we selected 37 from whom no recognized enteropathogens, except classic enteropathogenic Escherichia coli, were identified. For comparison, we also examined 37 matched-control infants without diarrhea seen at the same hospital setting. This paper had the purpose to determine the prevalence of localized, diffuse, and aggregative-adhering E. coli strains in both groups. Three to five fecal E. coli colonies, of each case and control, were tested individually for adherence to HeLa cells by using the one step 3-h incubation assay. Strains of E. coli showing localized adherence were found significantly more often in patients (37.8%) than in controls (13.5%), p < 0.02, and they were practically confined to EPEC serovars 055:H-, 0111:H2, and 119:H6. In contrast, E. coli isolates exhibiting the diffuse or aggregative patterns of adherence were restricted to non-EPEC serogroups and were more frequently encountered among controls. PMID- 1308563 TI - DOT-dye-immunoassay for the diagnosis of schistosomiasis mansoni. AB - A new serological assay dot-dye-immunoassay (dot-DIA) was evaluated for the diagnosis of schistosomiasis mansoni. This method consist of four steps: (a) biding of antigens to a nitrocellulose membrane (NC); (b) blocking of free sites of the NC; (c) incubation in specific primary antibody; (d) detection of primary antibody reactivity by color development using second antibody coupled to textile dyes. Sera from 82 individuals, 61 with Schistosoma mansoni eggs in the stool and 21 stool negative were tested by ELISA, dot-ELISA, and dot-DIA. A high level of agreement between the methods tested was observed for all sera tested: ELISA x dot-ELISA: 95.1%, ELISA x dot-DIA: 92.7% and dot-ELISA x dot-DIA: 97.6%. In this study, dot-DIA proved to be a feasible, sensitive, rapid and practical test for the diagnosis of schistosomiasis. PMID- 1308564 TI - Infection of Anopheles darlingi fed on patients infected with Plasmodium vivax before and during treatment with chloroquine plus primaquine in Costa Marques, Rondonia, Brazil. AB - Five patients with asexual and sexual parasites of Plasmodium vivax were treated orally with 600 mg chloroquine diphosphate (hour 0) followed with 300 mg at 8, 24 and 48 h later. Primaquine phosphate, 15 mg, was administered concurrently at h 0 and at 24 h intervals for 14 days. Anopheles darlingi were fed before the first dose (h -0.5) and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60 and 72 h later. Mosquitoes were examined for oocysts on day 8 and for sporozoites on day 15 after infection. Four of the five patients studied were still infective to mosquitoes from 1-5 h after the first dose of chloroquine plus primaquine. One of these and one other patient, who vomited 15 min after the first dose, became infective again at hours 10 and 12, respectively. Once produced, oocysts in mosquitoes fed on patients before, during and after chloroquine plus primaquine treatment appeared normal and produced sporozoite infected salivary glands. In view of these data, it is concluded that primaquine demonstrated rapid gametocytocidal activity and should be administered concurrently with chloroquine to reduce vivax malaria transmission. PMID- 1308565 TI - Malaria seroepidemiology: comparison between indirect fluorescent antibody test and enzyme immunoassay using bloodspot eluates. AB - Blood sampling on filter paper is a current practice in malaria seroepidemiological studies by indirect fluorescent antibody test (IFAT). There is, however, scant comparative information about the use of bloodspot eluates for detection of malarial IgG antibodies simultaneously by IFAT and enzyme immunoassay (ELISA). Here we report data obtained by both serological methods done on 219 bloodspot eluate samples collected in a rural community in Brazilian Amazon Basin (Alto Paraiso, Ariquemes municipality) where malaria is endemic. Plasmodium falciparum and P. vivax thick smear antigens were used in the IFAT; a detergent-soluble P. falciparum antigen was prepared for ELISA. Substantial agreement of results (Kappa coefficient k = 0.686) was observed when P. falciparum antigen was used in both tests, and IFAT titers were found to be strongly correlated to ELISA antibody units (Spearman correlation coefficient rs = 0.818, p < 0.001). Only moderate agreement (k = 0.467) between IFAT with P. vivax antigen and ELISA with P. falciparum antigen was observed. Spearman correlation coefficient value between quantitative results (IFAT titers and ELISA antibody units) in this case was numerically lower (rs = 0.540, p < 0.0001). Our results suggest that, with P. falciparum antigen, both IFAT and ELISA performed on bloodspot eluates are equivalent for seroepidemiological purposes. PMID- 1308566 TI - Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells. AB - Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and, in axenic medium, dose-dependent inhibition of amastigote and, to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxicity between antitrypanosomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypotheses for the mechanism of action of phenothiazines are discussed. PMID- 1308567 TI - A new host of Trypanosoma cruzi from Jujuy, Argentina: Octodontomys gliroides (Gervais & D'Orbigny, 1844) (Rodentia, Octodontidae). AB - To identify wild hosts of Trypanosoma cruzi, surveys were conducted in the subandean valleys of Jujuy Province, Argentina, between June 1986 and March 1987. Seventy two mammals from 13 different species were examined by xenodiagnosis. Fifty two of them were mostly rodents trapped at the localities of Maimara, Leon and Tilcara, and the remainder had been kept in captivity at the Estacion Biologica Experimental, in Jujuy. Trypanosoma cruzi infection was detected only in 2 Octodontomys gliroides (2 pos./8 exam. 25%) from all 72 examined mammals. Isolates were called Octodontomys Argentina 1 and 2 (OA1 and OA2). Both infected animals were caught at the archaelogical ruin of Pucara, at Tilcara. Repeated searches for triatomines in the ruin itself and in neighbour houses rendered negative results. Groups of mice inoculated with either OA1 or OA2 isolates became infected between 7 (OA1) to 12 days (OA2) postinoculation PI. Parasitemia peaks were observed between day 12th-14th PI. Scarce amastigote nests were found in myocardium and skeletal muscle. Mortality was observed only for mice inoculated with OA1. Isoenzyme patterns of OA1 and OA2 were identical to one found in dogs and slightly different from that of human parasites in Argentina. Bones from Octodontomys sp., were recently found in a cave, dated 10200-8600 BC, in Pumamarca, near Tilcara, Jujuy. There are evidences that O. gliroides cohabited with man in ancient times and was associated to the domestic cycle of T. cruzi transmission, playing a role like that of domestic caves in Bolivia. PMID- 1308568 TI - Description of Leishmania equatorensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting arboreal mammals in Ecuador. AB - Characterization is given of a new parasite, Leishmania equatorensis sp. n., which was isolated from the viscera of a sloth (Choloepus hoffmanni) and a squirrel (Sciurus granatensis), captured in humid tropical forest on the Pacific Coast of Ecuador. Data based on biological and molecular criteria, as well as numerical zymotaxonomical analysis, indicate that this parasite is a new species of the L. braziliensis complex. L. equatorensis is clearly distinguishable from all other known species within this complex, using the following molecular criteria: reactivity patterns with specific monoclonal antibodies, isoenzyme electrophoresis, and restriction-endonuclease fragment patterns of kinetoplast DNA (k-DNA). PMID- 1308569 TI - Development of Leishmania (Viannia) braziliensis vianna, 1911 in Lutzomyia intermedia (Lutz & Neiva, 1912) (Diptera:Psychodidae:Phlebotominae) under experimental conditions. AB - The development of Leishmania (Viannia) braziliensis in experimentally infected Lutzomyia intermedia, showed colonization of the hindgut from 48 h after the infective blood-meal, and the migration of flagellates to the foregut, with a massive infection of the cardia at the 5th day post infection. Up to 10 days following the infective blood-meal, very few parasites were seen in the pharynx and cibarium. The role of L. intermedia as a vector of cutaneous leishmaniasis is discussed according to the established criteria. PMID- 1308570 TI - Rapid in vitro detection of HIV-1-specific antibody secretion by cells-culture with virus antigens. AB - The present report describes an alternative method for in vitro detection of HIV 1-specific antibody secretion in 24h of culture employing as stimulant of peripheral blood mononuclear cells the disrupted inactivated whole virus adsorbed onto microwells in a commercial ELISA kit plates. The results obtained from this technique have showed high sensitivity and specificity since it was capable of detecting HIV-1 infection early after birth. There were neither false-positivity nor false-negativity when blood samples obtained from HIV-1 seronegative asymptomatic individuals, and HIV-1 seropositive adult patients were analyzed. This rapid, low cost, simple, highly sensitive and specific assay can be extremely useful for early diagnosis of pediatric HIV infection. PMID- 1308571 TI - Influence of short time exposure to an insect growth regulator, hexaflumuron, on mortality and adult emergence of vector mosquitoes. AB - Hexaflumuron, an insect growth regulator (IGR), was found to greatly affect the development of immatures and emergence of adults of three species of vector mosquitoes, Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi, when larvae were subjected to short time exposure of < or = 1 h. This IGR could completely prevent adult emergence even at a minimum exposure time of 10 min at 0.001, 0.01 and 0.1 mg/l. On treatment, larval and pupal mortality as well as varying degrees of morphogenetic abnormalities were induced in immatures and adults of the three species. Four weeks of control achieved in a slow moving sullage canal breeding Culex quinquefasciatus indicates that this IGR can be of use in such breeding habitats. PMID- 1308572 TI - The threat of reintroduction of natural transmission of Chagas' disease in Bambui, Minas Gerais State, Brazil, due to Panstrongylus megistus. AB - In the Epidemiological Surveillance Program in the county of Bambui, Minas Gerais, between August 1986 and December 1988, 154 Panstrongylus megistus were captured by the local population in both peridomicile and intradomicile environments. Fifteen (9.8%) of the P. megistus harboured Trypanosoma cruzi. Precipitin tests showed that the most frequent triatomine blood meal sources were birds, but other sources were dogs, men and cats. The isoenzyme characterization of 13 T. cruzi strains showed that six belonged to zymodeme Z1, corresponding to the wild cycle parasites, and seven belonged to zymodeme Z2, corresponding to parasites isolated from chronic chagasic patients (domestic cycle). As P. megistus were found to be naturally infected by parasites from both cycles. They are clearly able to transmit T. cruzi from the wild cycle to the domestic cycle. Furthermore the capacity of P. megistus in colonizing houses was observed in one residence, vacant for several years, in which 153 triatomines were captured. The data show the possibility of P. megistus reintroducing the natural transmission of Chagas' disease in the county if Epidemiological Surveillance is interrupted. PMID- 1308573 TI - Antigens of Toxoplasma gondii in a AIDS patient urine detected by coagglutination. PMID- 1308574 TI - Methyl-alpha-galactoside enhances the mitogenicity of the lectin jacalin. PMID- 1308575 TI - Partial characterization of Leishmania chagasi promastigote peptidases. PMID- 1308576 TI - Detection of houses infested with triatomines in Damianopolis Goias, Central Brazil. PMID- 1308577 TI - Rapid procedure for mycobacterial plasmids visualization. PMID- 1308578 TI - Atrial natriuretic factor in experimental acute Chagas' disease. PMID- 1308579 TI - [Hormones in milk]. AB - A short review of the presence of hormones and tissues growth factors in milk during various stages of lactation. On comparative grounds, their possible physiological importance for the neonate is discussed. PMID- 1308580 TI - [Attempts at reconstitution of skin continuity]. AB - Biological and clinical principles of living skin equivalents preparation and application are reviewed. Different models of living skin equivalents, based on both autogenic of allogenic elements, are described. PMID- 1308581 TI - [The importance of inflammatory mediators in immune injury of renal glomeruli]. AB - The article reviews contemporary state of knowledge pertaining to the pathogenesis of immune glomerular injury with particular emphasis on mediation of the inflammatory phase of glomerulonephritis. Distinct classes of humoral and cellular mediators are analysed with regard to their participation in experimental and human glomerulonephritis. PMID- 1308582 TI - [Role of serpins in regulation of hemostasis]. PMID- 1308583 TI - [Antineoplastons--structure, chemical properties and mechanism of activity]. PMID- 1308584 TI - [Long-term results of therapy of patients with diabetes mellitus and secondary resistance to sulfanilamides]. AB - Three groups of patients suffering from diabetes mellitus with secondary sulfanilamide resistance (SS) were observed. The first group was given sugar lowering drugs since the disease was diagnosed, the second group -- insulin plus hypoglycemic drugs, the third group -- insulin injections. The patients were followed up for 6-10 years, from the time of SS development -- 4.6 years. Stable compensation of diabetes mellitus was better achieved with combined therapy including sugar-lowering drugs per os and insulin, a dose of insulin being less by 22 units than in patients on insulin only. Progression of diabetic angiopathies was also less noticeable in the second group on combined therapy. The most unfavorable course of diabetic angiopathies and their progression were observed in the first group on sugar-lowering drugs per os. PMID- 1308585 TI - [Predictors of non-insulin-dependent diabetes mellitus]. AB - A random sampling of males and females aged 20 to 69 (1125 males and 1243 females), residing in Moscow, were investigated. The first screening was in 1979, the final one--in 10 years. The program of the first screening included anthropometry, evaluation of the CVS, carbohydrate and fat metabolism, studies on hereditary aggravation with regard to diabetes mellitus (DM); the program of final screening included the state of carbohydrate metabolism. Data processing was done using methods of multidimensional analysis. Independent signs to be used as predictors of noninsulin dependent diabetes mellitus were shown to be the age of 40 and older, a general GTT index of 16, and atherogenicity coefficient values of 3.5 and lower in men, and the presence of dyslipoproteinemia in women. PMID- 1308586 TI - [Insulin-like growth factor I in patients with newly detected insulin-dependent diabetes mellitus]. AB - Levels of insulin-like growth factor 1 (IGF-1) or somatomedin C were investigated in 12 subjects with only the onset (3-18 mos.) of IDDM. These levels were low as compared to control values (213 + 65 and 450 + 40 ng/ml) and vice versa, growth hormones levels were higher than those in control subjects (14.0 + 8.0 and 7.5 + 1.2 ng/ml). In one month after intensified insulin infusion and three daily injections, the ratio is smoothed (IGF-1 -- 320 + 20 during CSII; 280 + 12 ng/ml during conventional insulin therapy and GH -- 10.0 + 1.2 for CSII and 15.0 + 1.7 ng/ml for CIT). The disturbed GH/IGF-1 ratio correlated with the glycemia level (r = 0.65). A close connection was established between the levels of IGF-1 and C peptide concentrations in patients with IDDM onset (r = 0.70, p < 0.05), making it possible to influence beta-cell proliferation and to maintain DM remission. PMID- 1308587 TI - [Glycosylation products in the early diagnosis and prognostic evaluation of carbohydrate metabolism disorders]. AB - HbAIc and FA were investigated as markers in the diagnosis of early carbohydrate metabolic derangements. A group with normal TSH and a high concentration for glycosylation products was singled out. Carbohydrate metabolic derangements in 89 per cent showed a tendency to progression. Interrelationship between glycemia and PH was noted. The diagnostic and prognostic importance of HbAIc and FA was determined, and their combined use for single investigation of carbohydrate metabolism was recommended, making it possible to exclude "accidental" latent transitory hyperglycemia. TSH determination at early stages can be of low informative value, whereas HbAIc and FA measurements can detect disorders of carbohydrate metabolism early enough. PMID- 1308588 TI - [Early development of diabetic microangiopathy in young patients with newly detected diabetes mellitus]. PMID- 1308589 TI - [Myocardial involvement in hyper- and hypothyroidism]. AB - The paper is devoted to early myocardial pathology in patients with hyper- and hypothyroidism (15 patients with diffuse toxic goiter and 18 patients with primary hypothyroidism). They were investigated by radionuclide scintigraphy of the myocardium with -201TlCl. The myocardium in thyroid pathology was shown to suffer from dystrophic disorders, determined by metabolic derangements. The absence of disturbed perfusion processes in the myocardium and a diffuse decrease in metabolic activity of cardiomyocytes were revealed. Similar changes were found in patients without signs of myocardial involvement on ECG. PMID- 1308590 TI - [State of the endocrine and cardiovascular systems in patients with somatotropin producing hypophyseal adenoma]. AB - Altogether 16 persons with STH-producing hypophyseal adenoma were investigated by tacho-oscillography, total rheography, blood taken from the ulnar vein, a radioimmunoassay to determine the levels of STH, ACTH, cortisol, deoxycorticosterone, aldosterone, T3, T4, vasopressin, prostaglandin E2, 6-keto prostaglandin F1 alpha, and plasma renin activity. Acromegalic patients demonstrated an elevated level of STH, and prostaglandin E2 secretion was inhibited. Two groups of patients were singled out according to the hemodynamic state: the 1st group was characterized by a hyperkinetic type of circulation and normotension of borderline hypertension; the 2nd group was characterized by hypokinetic circulation, increased vascular resistance, labile or stable arterial hypertension. The interrelationship of hemodynamic and hormonal indices was unnoticed. It has been assumed that of pathogenetic importance in the development of arterial hypertension is depletion of E2 production, and at early stages--body liquid retention resulting from hypersomatotropinemia. PMID- 1308591 TI - [Anthropometric indices of newborns and hormone levels in various periods of ontogenesis]. AB - The relationships between anthropometric indices and the hormonal status in ontogenesis were investigated in newborns (137 girls and 151 boys aged 1.5-15); the venous blood levels of cortisol, corticosterone, testosterone, estriol, estradiol, progesterone, triiodothyronine, thyroxin, thyroxin-binding globulin, insulin and somatotropic hormone were determined by radioimmunoassay. At the time of investigation all the infants were practically healthy. Information on body mass and length was obtained from form 112 (Child's Development history). The results have shown that testosterone in boys was genetically determined stronger than in girls. Gene control of body mass and length in the intrauterine period is exercised with the help of the endocrine system. Periodic changing of the dominant genes at subsequent stages of ontogenesis leads to a changed role of certain hormones, directly regulating growth processes. PMID- 1308592 TI - [Feasibility of predicting the dynamics of human body mass]. AB - An original mathematical model of human energy exchange was developed and implemented on a PC. Energy exchange of healthy volunteers on a free diet and physical activity was simulated by inputting examinees' individualized parameters in the model: total body mass, fatty and lean tissue, nutritional energy capacity, power inputs. The main purpose was to study the reliability of prediction of the time course of total body mass with relation to a dietary caloric value and physical activity of an examinee, which was found to be necessary for working out an optimum metabolic diet, e.g. for patients with diabetes mellitus and adiposity. The authors propose a complete text of a computer program which can be used in research institutes and hospitals. PMID- 1308593 TI - [Surgical treatment of autoimmune thyroiditis (lecture)]. PMID- 1308594 TI - [An algorithm for the diagnosis and treatment of Itsenko-Cushing disease]. PMID- 1308595 TI - [Major public health tasks in fulfilling the Saint Vincent's declaration, aimed at improving the quality of therapeutic and preventive care of patients with diabetes mellitus. I]. PMID- 1308596 TI - [Role of physical exercise in compensation of diabetes mellitus]. PMID- 1308597 TI - [Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil]. AB - Biocyclic diterpenoids--salvin, salvicin and salvifolin, administered per os to rats at a dose of 50 mg/kg show marked hypoglycemic activity in intact animals as well as in animals with experimental hyperglycemia developing against a background of GTT (3000 mg/kg intraperitoneally) or alloxan (150 mg/kg subcutaneously). They are superior to adebit but inferior to maninil. Prophylactic and therapeutic administration of these compounds ensure the preservation of islet beta-cells in animals with alloxan diabetes. PMID- 1308598 TI - [Effect of experimental hyper- and hypoinsulinemia on the level of cholesterol lipoproteins in aging rats]. AB - A study was made of the effect of hyper- and hypoinsulinemia on blood serum lipoproteins of 5-6-month and 24-26 month old rats. Total cholesterol levels, cholesterol fraction concentration in lipoproteins, the level of insulinemia, and age showed correlation. Administration of insulin had a positive effect on the serum lipid spectrum, increasing the HDL-C content in aged animals. In alloxan diabetes, VLDL-C concentration in serum was on the increase. Alterations were more pronounced in young rats. PMID- 1308599 TI - [Effects of chronic surfagon administration on secretion of luteinizing hormone and morphofunctional state of the testes in Papio hamadryas]. AB - The paper is concerned with the results of a study of the effects of chronic (12 weeks) subcutaneous infusion of surfagon (D-Ala6, des-Gly10-ethylamide of LH-RH, a daily dose of 3 micrograms/kg of body mass) using osmotic mini-pumps on hormonal function of the hypophyseogonadal system, spermatogenesis and testicular histology in experiments on Papio Hamadryas. Prolonged infusion of surfagon through short-term transient activation of the hypophyseogonadal system was shown to cause inhibition of the basal secretion of LH-RH and testosterone, induction of hypophyseal desensitization to native LH-RH, development of oligo- and azospermia. Inhibited function of the testes was accompanied by noticeable changes in their histological structure (suppression of germinative cell division, narrowing of the seminiferous tubules, moderately transient fibrosis of connective stroma). Neither focal block of spermatogenesis nor foci of calcification or necrosis (observed in rats subjected to prolonged infusion of LH RH agonists) were observed in Papio Hamadryas. All changes in the reproductive system (including gonadal histology), induced by chronic infusion of surfagon, were of reversible nature. PMID- 1308600 TI - [Corticosterone level in testes of rats in varying adrenal functional activity]. AB - The presence of corticosterone in rat testes was demonstrated by combining HPLC and RIA techniques. The presence of the hormone was also taken into account. The testicular corticosterone content was shown to depend upon the functional activity of the adrenals and to diminish acutely after adrenalectomy. Analysis of correlation between the concentration of the hormones in the plasma and testes has shown corticosterone to be formed by testicular cells. PMID- 1308601 TI - [Enhanced sensitivity of pituitary cells to corticosteroids in neonatal rats]. AB - The effects of corticosteroids on pituitary cells, obtained from developing rats of different ages, were studied during long-term (3-4 days) incubation. Dexamethasone, cortisol and aldosterone inhibited the rate of DNA synthesis in primary cultures of pituitary cells from neonatal and pup rats more efficiently than in cell cultures of prepubertal and adult animals. Moreover, the above mentioned corticosteroids inhibited total protein biosynthesis in pituitary cells of infantile rats and did not change significantly this index of functional activity in cells of prepubertal and adult animals. In separate experiments steroid specificity of glucocorticoid action was examined in detail: estradiol and testosterone did not change the rates of macromolecule synthesis in neonatal pituitary cells whereas progesterone possessed a weak inhibitory effect that was, however, far less marked as compared to the effect of corticosterone. It has been concluded that neonatal rat pituitary cells demonstrate enhanced sensitivity to anti-proliferative and catabolic action of corticosteroids. PMID- 1308602 TI - [Morphofunctional state of the rat supraoptico-neurohypophyseal system in hypoparathyroisis]. AB - Volumes of nuclei and nucleoli of neurosecretory cells of the hypothalamic supraoptic nucleus were investigated morphometrically, and the amount of neurosecretion in the posterior hypophyseal lobe was determined photometrically in rats at varying time of parathyroprivic hypocalcemia. The data obtained were indicative of increased function of the hypothalamic supraoptic nucleus on the 5th day of parathyroprivic hypocalcemia and a decrease in the amount of neurosecretion in the posterior hypophyseal lobe that can be interpreted as a sign of an increased discharge of neurosecretion into the blood flow. A decrease in function of neurosecretory cells of the supraoptic nucleus in parallel with an increase in the amount of neurosecretion in the posterior hypophyseal lobe on days 15 and 30 of development of parathyroprivic hypocalcemia indicated retention of a discharge of neurosecretion. Return of neurosecretion to normal tended to occur on day 60. PMID- 1308603 TI - Anti-inflammatory effect of human placental extract: a biochemical mechanistic approach. AB - Significant increase of liver succinic dehydrogenase (SHD) activity was produced by carrageenin-induced edema in rats. Pretreatment with human placental extract "Placentrex" inhibited the increased liver SHD activity in a dose-dependent manner. "Placentrex" was found to have no effect on the liver SHD activity in normal rats. Furthermore, heat-induced erythrocyte lysis was inhibited to a substantial extent by "Placentrex" and was found to be almost dose-responsive. However, adenosine diphosphate (ADP)-induced platelet aggregation and trypsin activity were not changed in vitro by the "Placentrex". No alkaline phosphatase activity was found in this preparation. All these studies indicate that the membrane stabilization and depletion of adenosine triphosphate (ATP) synthesis may be the basis of anti-inflammatory effect of this drug. PMID- 1308604 TI - [Obstetric care in cardiopathic pregnant women]. AB - Heart diseases in pregnancy represent the main not-obstetrical cause of death and the fourth in absolute way. Cardiopathies should be diagnosed before pregnancy also to try a possible correct contraception. After discussing the modifications of the cardiovascular apparatus in a healthy pregnant subject, the authors dwell upon the modifications affecting heart patients in pregnancy. Particular attention is given to the therapeutical interruption in pregnant cardiopathic patients. PMID- 1308605 TI - [The vaginal ecosystem in a group of asymptomatic women]. AB - In physiological conditions the vaginal flora reflects, from a quantitative a quality point of view, the metabolical, local and hormonal situation of the woman. The vaginal infections could be facilitated by borderline conditions, between physiology and pathology. The prevention may contribute to limit the development and diffusion of infections. For this reason, we have examined, with a bacteriological and symptomatological test who 50 women requested a gynecological control for different reasons from vulvovaginiti. The results suggest that women often silently accept borderline conditions. PMID- 1308606 TI - [Renal physiopathology in pregnancy]. AB - The authors examined the main anatomo-functional modifications of kidneys during pregnancy, through the analysis of "flux" and glomerular and tubular "functions". Among the modifications occurring in pathological conditions they included pregnant patients with only one kidney, patients affected by kidney calculosis, anomalies of urinary tract and patients who underwent kidney transplant. PMID- 1308607 TI - [The relation between dysmenorrhea and hot flash in a group of women in climacteric]. AB - Hot flushes in climacteric age can cause noticeable discomfort to those who have them. This functional disturbance confirms the strong relationship between the gonadic steroids and the central neurotransmitters. These complex mechanisms which control reproductive functions limit our knowledge of the pathogenesis of hot flushes. The possible intervention of prostaglandins in the rising of this disturbance and their participation in dismenorrhea have raised the hypothesis that the prostaglandins may be the common denominator in the development of dysmenorrhea in fertile age women and of hot flushes in climacteric age women. Under this context, we examined a number of women in menopause to determine if they suffered with dysmenorrhea in fertile age. PMID- 1308608 TI - [Epidermoid cyst of the spleen. Description of a clinical case]. AB - A case of epidermoid cyst of the spleen in a young man is reported. The importance of the echotomography and CT for diagnosis of this unusual pathology is pointed out. The role of splenectomy as first choice in the treatment of splenic cysts is emphasized. PMID- 1308609 TI - [Darier-Ferrand dermatofibrosarcoma. General aspects and personal experience]. AB - The Darier-Ferrand dermatofibrosarcoma is a cutaneous lesion with a clinic and recidivant progress that appears in both sexes in the same measure. The metastasis are rare. The authors describe a kind of treatment effected in 13 cases arrived to their observation. PMID- 1308610 TI - [The use of imipenem-cilastatin in acute ORL infections]. PMID- 1308611 TI - Effect of sulpiride on ischemia- and reperfusion-induced heart damage, in rats. AB - In an experimental model of heart ischemia, obtained in anesthetized rats with the permanent ligature of the left anterior descending coronary artery, the intravenous (iv) injection of I-sulpiride (6-25 micrograms/kg) dose-dependently reduced the lethality rate, the incidence and severity of ventricular dysrhythmias and infarct size during the early phase of ischemia (first 30 min after coronary ligation). Lethality and there incidence and duration of ventricular dysrhythmias were also significantly reduced by the same IV doses of I-sulpiride in a model of coronary reperfusion. These results show that a specific dopamine antagonist is able to limit ischemia- and reperfusion-induced myocardial damage and suggest that endogenous dopamine may exert a deleterious effect in such conditions. PMID- 1308612 TI - [The treatment of pancreatic pseudocyst]. PMID- 1308614 TI - [Anorectal malformations. Advances and the current focus]. PMID- 1308613 TI - [Carcinoma of the anal area]. PMID- 1308615 TI - [The current state of the surgery of portal hypertension]. AB - Surgery for bleeding portal hypertension has evolved widely in the last decades. The surgical procedures that preserve portal blood flow are the first operative choice for well selected patients. Operative procedures that deprive the portal blood flow to the liver, are most likely to promote deterioration of liver function in the late postoperative period. The operation most frequently performed are the selective shunts (Warren) and the thoraco abdominal devascularization (Sugiura). The best results are obtained in patients with a good liver function that are operated in an elective fashion. Non-selective shunts have a restricted indication and low diameter porto systemic shunts are still under evaluation. The combination of drug therapy and/or sclerotherapy with surgery appears to improve survival. Liver transplants are indicated for those patients with associated liver failure. For patients with good liver function, surgery is the therapy of choice. PMID- 1308616 TI - [The liver transplant]. PMID- 1308617 TI - [Surgery by laparoscopy]. PMID- 1308618 TI - [Mechanical suturing apparatus. Its history, development and experience at the Central Military Hospital]. PMID- 1308619 TI - [Strategies in the management of Barrett's esophagus]. PMID- 1308620 TI - [Advances in the surgical treatment of esophageal cancer]. PMID- 1308621 TI - [Proximal gastric vagotomy]. AB - The incidence of uncomplicated peptic ulcer disease has markedly decreased all around the world over the last two decades. The medical and surgical management of patients with peptic ulcer disease, has also changed with the use of more effective drugs. Currently, the objectives of ulcer surgery are to eradicate the disease, to leave the gastrointestinal digestive apparatus as normal as possible, and to achieve these goals with the lowest possible mortality and recurrence rates. Proximal gastric vagotomy is currently the procedure of choice for a large number of gastric surgeons in the treatment of patients with chronic duodenal ulcer, who have failed medical therapy. Its application in treating the complications of peptic ulcer disease, which represent the greater percentage of all operations done for peptic ulcer disease, is less well-tested. However, initial series report good results in selected patients. Proximal gastric vagotomy without a drainage procedure, is the latest contribution to ulcer surgery. The operative mortality, is nearly zero, the recurrence rate of 4% to 11%, and there is virtual absence of significant side effects. PMID- 1308622 TI - Thickening of the adrenal zona glomerulosa in dogs induced by oxodipine, a calcium channel blocker. AB - Subchronic effects of oxodipine, a calcium channel blocker affecting the adrenal gland of the dog, are described. Thirteen wk of treatment at a high dose (24 mg/kg/day) of oxodipine resulted in drug-induced thickening of the zona glomerulosa and increased stimulation of its secretory activity. It is postulated that subchronic administration of oxodipine at this dosage resulted in a decrease in blood pressure, with uninterrupted stimulation of the adrenal zona glomerulosa to release aldosterone, causing an increase in the width of this portion of the gland involving cellular hyperplasia. Support for this indirect effect is found in the increased presence of renin granules in the juxtaglomerular apparatus. PMID- 1308623 TI - Spontaneous brain and spinal cord/nerve neoplasms in aged Sprague-Dawley rats. AB - Primary malignant neoplasms of the brain and spinal cord occurred in 20/718 male (2.8%) and in 13/717 female (1.8%) Crl:CD Br strain Sprague-Dawley rats. Of 33 neoplasms, 30 were found in brain while 3 were in the spinal cord. In males and females, the most common brain neoplasm was astrocytoma (13 males, 9 females). Other neoplasms, granular cell tumor (1 male), mixed glioma (2 males, 1 female), reticulosis (1 male, 2 females), and oligodendroglioma (2 males), were especially uncommon. Spinal cord neoplasms included 2 schwannomas (1 male, 1 female) and an astrocytoma (1 male). The overall brain neoplasm incidence was similar for males (2.8%) compared to data compiled for this strain, and there was a 2-fold increase for females (1.8% vs 0.9%) compared to available incidence data. PMID- 1308624 TI - The histology and development of hepatic nodules and carcinoma in C3H/He and C57BL/6 mice following chronic phenobarbitone administration. AB - Male C3H/He and C57BL/6 mice were given diets containing sodium phenobarbitone (PB) to allow a daily intake of 85 mg/kg. Control and treated animals were killed at 5, 30, 40, 60, and 80 wk. Other mice were killed in extremis or at the end of the respective experiments: 91 wk for C3H/He and 100 wk for the C57BL/6 animals. A basophilic nodule was found in 1/5 control C3H/He mice at 30 wk; these nodules increased in number with time so that nodules of this type were found in approximately 70% of animals by 91 wk. Nodules were not found in control C57BL/6 mice until 80 wk, when they were found in 4% of mice. PB treatment markedly increased the number of hepatic nodules in both strains of mice. The additional nodule burden was due to the development of a second nodule type formed of large cells with a predominantly eosinophilic cytoplasm. C3H/He animals given PB for 60 wk and then returned to a control diet bore fewer nodules at 91 wk than treated mice killed at 60 or 91 wk. The cumulative incidence of carcinoma in control C3H/He and C57BL/6 mice was 28 and 4%, respectively. The incidence of carcinoma was not increased by PB treatment in either strain. It is concluded that both strains of mice behave in a qualitively similar way to PB administration, although they show considerable quantitative differences in terms of the time and number of nodules that develop. Furthermore, the increased nodule numbers associated with PB treatment were not accompanied by an increase in the number of carcinomas. PMID- 1308625 TI - Subacute toxicity of a halogenated pyrrole hydroxymethylglutaryl-coenzyme A reductase inhibitor in Wistar rats. AB - Wistar rats received an hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, a halogenated pyrrole designated PD 123244-15, orally by gavage for 14 days at 10, 50, 150, 300, and 600 mg/kg. Doses of 150-600 mg/kg caused death and marked systemic toxicity involving stomach, esophagus, liver, gonads, lymphoid tissues, and skeletal muscle. Histopathologic findings included hyperkeratosis in esophagus and forestomach, increased hepatic mitotic activity, ovarian follicular necrosis, testicular atrophy and arrested spermatogenesis, and skeletal muscle necrosis and regeneration. Elevated serum aspartate aminotransferase correlated with muscle necrosis and hepatocellular damage. Marked systemic effects associated with high plasma concentrations were consistent with toxicity defined for other HMG-CoA reductase inhibitors, with the exception of pathologic alterations in the esophagus and ovaries. Direct mucosal irritation may have contributed to forestomach and esophageal lesions induced by this halogenated pyrrole. PMID- 1308626 TI - The use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis to detect renal damage in Sprague-Dawley rats treated with gentamicin sulfate. AB - Renal toxicity is a common manifestation to the exposure of laboratory animals and humans to a wide range of xenobiotics. Traditional methods for evaluating renal damage by clinical chemistry such as blood urea nitrogen (BUN) and serum creatinine are not sensitive to early, mild changes. The use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to measure the molecular weight spectrum of urinary proteins allows for an evaluation of the functional changes associated with renal damage. The ability of the kidney to filter and reabsorb proteins is related to the functional ability of glomeruli and the proximal tubules. Gentamicin sulfate produces injury to the S-1 and S-2 segments of the proximal tubule in laboratory animals and humans. While severe damage to the tubules is associated with increased BUN, serum creatinine, and N-acetyl-beta glucosiminadase (NAG), mild injury is not detected by these means. The evaluation of urinary proteins by SDS-PAGE demonstrated renal toxicity at a dose of 6 mg/kg after 2 days of sc treatment. The NAG: creatinine ratio was shown to be elevated after 2 days of treatment at 63 mg/kg. The use of SDS-PAGE as described in this paper provides a sensitive method for detecting renal injury. PMID- 1308627 TI - Interpreting the Delaney Clause in the 21st century. PMID- 1308628 TI - The 7th Aspen Cancer Conference. Mechanisms of Toxicity and Carcinogenesis. Aspen, Colorado, July 18-22, 1992. Abstracts. PMID- 1308629 TI - Clinical pathology testing in toxicity studies. PMID- 1308630 TI - [Transportation and resuscitation of the premature newborn]. PMID- 1308631 TI - [Respiratory pathology of the premature infant]. PMID- 1308632 TI - [Neonatal resuscitation]. PMID- 1308633 TI - [Nursing care of the premature newborn]. PMID- 1308634 TI - [The premature infant and his family]. PMID- 1308635 TI - [The premature infant. A very fragile newborn]. PMID- 1308636 TI - [The premature newborn in the neonatal intensive care units. What kind of suffering? What kind of care in the unit?]. PMID- 1308637 TI - [Towards optimal nursing care]. PMID- 1308638 TI - [Diversification of infant nutrition]. PMID- 1308639 TI - [A sterile couple]. PMID- 1308640 TI - [Etiology and pathologies linked to prematurity]. PMID- 1308641 TI - Nutrition and education. IV. Clinical signs of malnutrition and its relationship with socioeconomic, anthropometric, dietetic and educational achievement parameters. AB - The objective of this study was to determine the prevalence of clinical signs of malnutrition, and to measure the interrelationship with socioeconomic, anthropometric, dietetic and educational achievement parameters. A random sample of 550 Chilean elementary and high school graduates (1:1), of both sexes (1:1), from public and private schools (1:1) and from high, medium and low socioeconomic status (SES) (1:1:1), was chosen in the Metropolitan Area of Santiago, Chile. SES was measured through the Graffar Modified Scale. Clinical signs of malnutrition were assessed according to Jelliffe. Nutritional status was determined by means of anthropometric measurements: percentages of weight/age (W/A), height/age (H/A) and weight for height (W/H) were compared with the WHO Tables; head circumference/age (HC/A) with the Tanner Tables, and branchial anthropometric parameters by applying the Frisancho norms. Standard procedures for the 24 hour dietary recall interviews were used to collect data, and adequacy of intake was assessed by the FAO/WHO pattern. Educational achievement (EA) was measured through the Achievement Evaluation Program, (AEP) and Academic Aptitude Test (AAT) in elementary and high school graduates, respectively. Results showed that apart from caries (87.5%), most prevalent clinical signs of malnutrition were dermatosis (13.4%), follicular hyperkeratosis type I (13.2%), nasolabial dyssebacea (7.9%), lustreless hair (7.7%), angular stomatitis (4.4%) and cheilosis (2.7%). The number of clinical signs of malnutrition was found inversely and significantly associated with SES, H/A, vitamin A and calcium intake, as well as with EA, besides registering a lower nutrient intake, specially for energy, riboflavin and niacin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308642 TI - [Anthropometric evaluation of the nutritional status of a elderly group from Madrid (Spain)]. AB - Body composition was assessed by means of anthropometry in a group of 75 elderly people (21 men and 54 women), aged 65 to 95 years (mean age 82.1 +/- 0.7) (x +/- SE), mean weight 58.5 +/- 1.7 kg and mean height 150.4 +/- 1.1 cm, which live in al Old People's Home in the Autonomic Community of Madrid. The average Quetelet Index 25.7 +/- 0.7 kg/m2 indicates a basically normal situation although there are 21% obese elderly with Quetelet over 30 kg/m2 and 12% of the cases with the index under 20 kg/m2. Even though the skinfold thickness in our population is inferior to the results obtained in other studies, the triceps skinfold is nearer the values given by other authors, and the suprailiac skinfold is completely different. This means that the elderly studied have less abdominal fat accumulation and more accumulation in arms and legs. This fat distribution can be beneficial in relationship to the risk of suffering several pathologies. Of the males, 15% and 22% of the females have their weight 25% and 30%, respectively, higher than their ideal weight. But there are also some of them with ponderal deficiency; by this means, 23% have 95% lesser than their ideal weight, indicating moderate malnutrition. A total of 16% have less than 85%, indicating medium malnutrition and 2 have less than 75% of the ideal weight, which is indicating of severe deficiency. With age, the measured height, weight, skinfolds, circumferences and diameters, the fat and lean body mass values decrease, the abdominal skinfold and the fat body mass decreasing significantly. Our results can contribute to increase knowledge as to the nutritional status and body composition of the Spanish elderly, and emphasize the coexistence of fat and ponderal excess with deficiencies of higher or lower importance. PMID- 1308643 TI - [Blood glucose, insulin, GH, and amino acids in rats receiving 3 levels of dietary proteins]. AB - The effect of dietary protein content on the variations in plasma insulin, GH, glucose and both gluconeogenic and branched-chain amino acids (BCAA) levels, was studied in Wistar rats. For 21 days animals consumed ad libitum diets containing 4% (LP group) 10% (MP group) or 20% (HP group) protein. Body weight gain and plasma concentrations of the glucose, insulin and both the insulin/glucose (I/G) and insulin/GH (I/GH) ratios varied directly with the protein content of the diet. In contrast the relationships between dietary protein content and GH levels, were inverse. These results indicate that an increase of energy yielding nutrients availability and an decrease of tissue sensitivity to insulin was produced as the protein content of the diet was increased. The increase of plasma aspartate, serine, histidine and alanine levels on LP group suggest a low gluconeogenic process, and the higher rate of BCAA on HP group against to MP and LP groups can be related to a lower tissue uptake. Both effects can be mediated by the tissular sensitivity to insulin. PMID- 1308644 TI - [Amaranthus mantegazzianus. Chemical composition and protein biological value]. AB - The objective of this work was to obtain the raw seed powder from Amaranthus mantegazzianus, the evaluation of its chemical and protein amino acid composition using certain biological indexes such as: net protein utilization (NPU), true digestibility (TD), biological value (BV), net protein ratio (NPR) and relative net protein ratio (RNPR). A protein content (N x 5.85) of 12.54 g/100g, and a chemical score (CS) (FAO/OMS/UNU 1985) of 74, represented by leucine as the first limiting amino acid were found. The biological test results obtained were: NPU = 54 +/- 6.4; TD = 81 +/- 7.4; BV = 67; NPR = 2.7 +/- 0.3 and RNPR = 60. No significant concentrations of the anti-nutrients studied were found. The high value of available lysine found is remarkable (48 mg/g protein). Therefore, it is concluded that this species could constitute an interesting potential source to supplement proteins which are deficient in this amino acid. PMID- 1308645 TI - [Extraction and characterization of grain prolamins of 6 sorghum Sorghum bicolor L. Moench cultivars]. AB - The purpose of this work was to isolate and characterize prolamines from grains of sorghum, by their solubility and molecular properties. One variety, Zaraza-1 (SV-V51), and five hybrids (Dekalb-55, Dekalb-64, Wac-5005, Pioneer-815B and Savanna-5) were used. The prolamines, called kafirins, were extracted with 70% isopropanol at 60 degrees C, and then fractionated by two methods: 95% ethanol and gel filtration with Sephadex G-200. The molecular weight was determined by electrophoresis in a discontinuous polyacrylamide gel with sodium dodecyl sulfate (PAGE-SDS). The alpha kafirin (soluble fraction in 95% ethanol), and 7.13% of the grain's total protein, and the beta kafirin represents 21.64% of kafirin (the insoluble fraction), represents 78.36% of the kafirin and 25.39% of total protein. Three fractions were obtained from the column fractionation, two important ones (A and C), and one (B) in a lesser amount. The proportion of these fractions varied between cultivars, so that in SV-V51, D-64 and Wac-5005, A is predominant, and in high tannin sorghum, C is the predominant one. Kafirins reduced with 2-mercaptoethanol were separated in four subunits with molecular weights of: 15,000, 21,300, 24,300 and 51,500 daltons. Unreduced kafirin showed a larger number of subunits (six) whose molecular weights were: 15,000, 24,300, 48,500, 69,000, 80,000 and 93,500 daltons. Reduced and kafirin showed the same number of subunits as those of nonfractioned kafirin reduced with 2 mercaptoethanol. PMID- 1308646 TI - [Chemical changes in sorghum during the extrusion and tortilla preparation process]. AB - Chemical changes that occur during preparation of instant sorghum flours processed by extrusion and during the preparation of tortillas, were studied. In the preparation process of instant flours and tortillas two flours were used: whole flour obtained from a sorghum cultivar genotype cmsxs 9A, and another one (20%) from decorticated sorghum flour cultivar, cmsxs 145. These flours were processed in Brabender laboratory extruder GNF/2 of a single screw, with a compression rate of 1:1 and extrusion temperature of 80, 100 and 100 degrees C in the 1st, 2nd, 3rd zones, respectively, with a 5 mm diameter and a screw rate of 130 rpm, flour with 15% moisture and 0.15 Ca(OH)2 concentration. The decorticated sorghum flours presented a lower content of ashes, protein, fiber, lipids, vitamins and minerals in comparison with the whole sorghum flours, due to a partial loss of pericarp and germ. Reduction of said components increased the starch percentage in the decorticated sorghum. The addition of alkali induced an increment in the calcium and ash content of instant flours and tortillas. The most affected components during the extrusion process were thiamine, calcium and the amino acids histidine, arginine and leucine. The more notorious changes in the cooking process for the preparation of tortillas were observed in the calcium, leucine, arginine, histidine and phenylalanine content. PMID- 1308647 TI - [Comparison of methods for determining corn hardness (Zea mays L.)]. AB - One of the most important intrinsic properties of corn kernels is hardness. Nowadays controversy exists as to which method is more accurate to measure this property. In the present study, therefore, several methods for measuring hardness in corn kernels are compared, for the purpose of finding the most appropriate one. A corn population ranking from hard to soft was tested. The methods tested were: endosperm texture (ET), pearling index (PI) floating index (FI), density (D), near infrared reflectance (NIR), test weight (Ph) and time required to grind the corn with the Brabender automatic micro-hardness (TDB) method. The floating index (FI) method was found to be the most suitable one for determining hardness of corn kernels. This method permitted determination of the differences existing in corn with hard, intermediate, and soft-textured endosperms, with low variation coefficients. The TDB and NIR methods were not appropriate to determine the hardness of corn kernels, showing high variability in the results. With the Ph and D methods it was difficult to distinguish between corn with hard, intermediate and soft texture endosperm. PMID- 1308648 TI - Recent trends in nutritional sciences. PMID- 1308649 TI - [Comparative study of the chemical composition and nutritive value of runner bean (Phaseolus coccineus) and of common bean (Phaseolus vulgaris)]. AB - Scarlet beans (Phaseolus coccineus) is an important food grain legume in the diet of rural populations living in the highlands of Mexico, Guatemala and other countries of Latin America. The present study was conducted to obtain more chemical and nutritive data on this grain legume, because of its importance in agricultural production systems and due to the role it plays in rural diets. Ten samples were purchased in the highland markets of Guatemala, to compare their physical, chemical and nutritive characteristics with three samples of common beans (Phaseolus vulgaris). A sample of 10 kg was used for nutritional studies, fed alone and in mixtures with maize. The results indicated that P. coccineus has greater weight as compared to P. vulgaris (0.74 vs. 0.18 g) and are larger in size (0.60 vs. 0.14 cc/grain). Seed coat percentage was 10.2% for P. coccineus as compared to 9.0% for P. vulgaris. The cooking time was 231 minutes for P. coccineus and 180 minutes for common beans. Seed coat thickness and permeability are different when comparing P. coccineus with P. vulgaris, since at 24 hr soaking time, P. coccineus absorbed 80% of its water weight as compared to 100% for common beans. In chemical composition) small differences were found between P. coccineus and P. vulgaris. The first had slightly more ether extract, crude fiber and ash content than the second. Amino acid content among the six samples of P. coccineus was quite variable, but its pattern was rich in lysine and limiting in sulfur amino acids. Cooking time at 3 hr gave a higher NPR than when cooked at atmospheric pressure for 5 hr, with protein values relative to casein of 69.2 and 60.0%, respectively. P. coccineus protein quality was improved by methionine supplementation, and it appeared to be better digested than that of P. vulgaris. Mixtures of high protein quality were obtained with 15% P. coccineus and 85% maize while common beans and maize mixed in a 30 to 20 ratio showed maximum protein efficiency. The digestibility of the P. coccineus/maize mixtures was higher than that of common beans and maize. PMID- 1308650 TI - Nutrition and education. III. Educational achievement and food habits of Chilean elementary and high school graduates. AB - The objective of this study was to correlate the educational achievement (EA) of Chilean elementary and high-school graduates with their food habits. For this purpose, a random sample of 550 schoolers from the Metropolitan Area of Santiago, Chile, graduating from elementary and high school (1:1) of both sexes (1:1), from public and private schools and from high, medium and low socioeconomic status (SES) (1:1:1), was selected. Food habits were determined through a specially designed questionnaire and defined as the frequency of consumption of the food groups, expressed as days per week. The EA was established through the Achievement Evaluation Program (AEP) and Academic Aptitude Test (AAT) in elementary-and high-school graduates-, respectively. Results revealed that EA was found significantly and positively correlated with the frequency of consumption of dairy products, meat products and eggs, in both elementary and high school graduates. A significant and inverse correlation between EA and the frequency of vegetables and fruits consumption was observed in both educational levels, and with miscellaneous products, only in elementary school graduates. Food habits explained 24.4% and 16.6% of the EA variance, in elementary and high school graduates, respectively. The frequency of consumption of dairy products was the independent variable with the greatest explanatory power in EA variance (approximately above 70% of the explained variance). These results are important to consider for educational planning focused on the School Feeding Program. PMID- 1308651 TI - Heparin-induced hematomas. PMID- 1308652 TI - Harpoon device for removal of obstructed balloon catheters. PMID- 1308653 TI - Reply to invited letter concerning: Left ventricular function changes after cardiomyoplasty in patients with dilated cardiomyopathy (J Thorac Cardiovasc Surg 1991;102:156-7) PMID- 1308655 TI - William Marsden (1807-1885). PMID- 1308654 TI - Results of colectomy in elderly patients with colon cancer, based on Medicare claims data. AB - Currently available estimates of outcomes following colon resection in elderly patients with colon cancer are based on series collected at academic medical centers. We used Medicare Part A claims and enrollment records of a 5% nationally random sample of elderly Medicare beneficiaries from 1983 to 1985 to estimate how patient age and sex affected perioperative mortality and 1- and 2-year survival rates among elderly patients undergoing a colon resection procedure for colon cancer. Among the 5,586 individuals in our data set, the overall perioperative mortality rate was 5.0%, ranging from 3.3% in beneficiaries 66 to 69 years of age to 9.3% in those 85 years of age and older. Men had a 31% higher perioperative mortality rate than women (5.8% versus 4.4%, p less than 0.05). The overall postoperative survival rates at 1 and 2 years were 72% and 63%, respectively, decreasing with increasing age, but were similar in men and women. This analysis provides age- and sex-specific estimates of outcomes following surgery for elderly patients with colon cancer that are more precise and have more potential for generalization than those that were available previously. PMID- 1308656 TI - Glass ampoules. PMID- 1308657 TI - TLVs for asbestos. PMID- 1308658 TI - Surgical treatment of persistent ductus arteriosus complicated by bacterial endocarditis. AB - A seven-year-old girl with persistent ductus arteriosus developed acute bacterial endocarditis with large vegetations in the ductus and the left pulmonary artery. Conservative management was not successful: repeated embolisation to the lungs necessitated operation during the acute endocarditis. Details of the operative technique are presented and discussed. PMID- 1308659 TI - Erosion of buttress following bladder neck suspension. PMID- 1308660 TI - Solvent effects on chemical processes. I: Solubility of aromatic and heterocyclic compounds in binary aqueous-organic solvents. AB - The standard free energy change (delta G0) for equilibrium dissolution in binary solvent mixtures is written as a sum of effects arising from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect). The general medium effect is given by gA gamma, where g is a curvature correction factor to the surface tension (gamma) and A is the molecular cavity surface area. A new feature is the definition of gamma to be that value appropriate to the equilibrium mean solvation shell composition. The solvation effect is modeled by stoichiometric stepwise competitive equilibria between the two solvent components for the solute. The intersolute effect includes the crystal energy and solution phase interactions. In this work, water was solvent component 1, and various miscible organic cosolvents served as solvent component 2. Relating all data to the fully aqueous solution gives an explicit expression for delta M delta G0, the solvent effect on the free energy change, as a function of the mole fractions x1 and x2. This function is a binding isotherm. Nonlinear regression leads (for a two-step solvation scheme) to estimates of the solvation exchange constants K1 and K2 and the parameter gA. This relationship was applied to 44 systems comprising combinations of 31 solutes and eight organic cosolvents. Curve fits were good to excellent, and most of the parameter estimates had physically reasonable magnitudes. PMID- 1308661 TI - Focal midbrain tumors in children. AB - The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive hydrocephalus (50%) or symptoms and signs caused by pressure on the tegmentum and cerebral peduncles. The lesions are confined to the tectal plate or tegmentum with possible extension upward to the thalamus and downward to the pons, displacing but not invading these structures. The edges of the tumor are well defined, and the large majority have a solid consistency with intense regular enhancement after intravenous contrast. Radical resection is hardly ever feasible in brain stem tumors, but in this series, significant reduction of the tumor mass was obtained in 75% of the patients, with no surgical mortality and minimal surgical morbidity and with the majority of patients showing clinical improvement postoperatively. All tumors were nonpilocytic, low-grade astrocytomas. Six patients received adjunctive radiotherapy. The mean follow-up period is 2.5 years, and all patients are alive and doing well. We conclude that focal midbrain tumors in children appear to be a distinct subgroup of brain stem tumors and are very amenable to surgical resection with an excellent long-term prognosis. PMID- 1308662 TI - Which medical schools produce rural physicians? AB - OBJECTIVE: To examine the hypothesis that medical schools vary systematically and predictably in the proportion of their graduates who enter rural practice. DESIGN: The December 1991 version of the American Medical Association Physician Masterfile was used to examine the rural and urban practice locations of physicians who graduated from American medical schools between 1976 and 1985. Selected characteristics of the medical schools--including location, ownership, and funding--were linked to the Physician Masterfile. MAIN OUTCOME MEASURES: The percentage of the graduates from each medical school who were practicing in rural areas in December 1991, disaggregated by physician specialty. RESULTS: Of the practicing graduates from our study, 12.6% were located in rural counties; family physicians were much more likely than members of other specialties to select rural practice, particularly in the smallest and most isolated rural counties. Women were much less likely than men to enter rural practice. Medical schools varied greatly in the percentage of their graduates who entered rural practice, ranging from 41.2% to 2.3% of the graduating classes studied. Twelve medical schools accounted for over one quarter of the physicians entering rural practice in this time period. Four variables were strongly associated with a tendency to produce rural graduates: location in a rural state, public ownership, production of family physicians, and smaller amounts of funding from the National Institutes of Health. DISCUSSION: The organization, location, and mission of medical schools is closely related to the propensity of their graduates to select rural practice. Increasing policy coordination among medical schools and state and federal governmental entities would most effectively address residual problems of rural physician shortages. PMID- 1308663 TI - Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial. AB - OBJECTIVE: To determine the clinical and endoscopic response of candida esophagitis to antifungal therapy and to compare the two oral antifungal agents, fluconazole and ketoconazole. DESIGN: Multicenter, randomized, double-blind trial. SETTING: Fifteen U.S. centers including university, private practice, and county hospital settings. PATIENTS: A total of 169 patients with the acquired immunodeficiency syndrome (AIDS); odynophagia, dysphagia, or retrosternal pain; white esophageal plaques at endoscopy; and pseudohyphae on esophageal brushings or biopsies. INTERVENTION: Patients were randomly assigned to fluconazole (100 mg/d) or ketoconazole (200 mg/d). Doses were doubled at week 1 or 2 if no symptomatic improvement had occurred during the preceding week. Therapy was continued for 2 weeks after resolution of symptoms or for a maximum of 8 weeks. MEASUREMENTS: Patients were clinically evaluated weekly, and laboratory tests were done every 2 weeks. Endoscopy was repeated within 5 days after the end of therapy. RESULTS: A total of 143 patients were clinically evaluable (assessed within 7 days after therapy), and 129 patients were endoscopically evaluable (endoscopy repeated after therapy). Endoscopic cure occurred in 91% of patients treated with fluconazole and in 52% of those given ketoconazole for a difference of 39% (95% Cl, 24% to 52%; P less than 0.001). Esophageal symptoms resolved in 85% of fluconazole-treated patients and in 65% of ketoconazole-treated patients for a difference of 20% (Cl, 6% to 34%; P = 0.006). Intention-to-treat analyses also yielded statistically significant differences for the comparisons listed above. Side effects were minimal and comparable in the two groups; only one patient in each group had therapy discontinued for adverse effects that were possibly related to the study medications. CONCLUSIONS: Fluconazole is associated with significantly greater rates of endoscopic and clinical cure than ketoconazole in patients with AIDS and candida esophagitis. Both drugs appear to be safe and well tolerated. PMID- 1308664 TI - Herpes zoster and human immunodeficiency virus infection. AB - The interaction of herpes zoster and the human immunodeficiency virus (HIV) was evaluated in a cohort study of 287 homosexual men with well-defined dates of HIV seroconversion and 499 HIV-seronegative homosexual men. The incidence of herpes zoster was significantly higher among HIV-seropositive men (29.4 cases/1000 person-years) than among HIV-seronegative men (2.0 cases/1000 person-years); the overall age-adjusted relative risk (RR) was 16.9 (95% confidence interval [CI], 8.7-32.6). When compared with that of age-matched population controls from 1945 to 1959, the incidence of zoster was significantly higher among seropositive men (RR, 26.7; 95% CI, 19.3-37.1) and slightly higher among seronegative men (RR, 1.85; 95% CI, 1.0-3.3); the latter may reflect increasing background rates over several decades. The risk of herpes zoster was not associated with duration of HIV infection and was not predictive of faster progression to AIDS. PMID- 1308665 TI - Multiply-resistant Enterococcus faecium. The nosocomial pathogen of the 1990s. PMID- 1308666 TI - Air reduction of an intussusception caused by a pathologic lead point in an infant. AB - Lead points that are the cause of an ileocolic intussusception are rare in infants [1], as is successful reduction using barium [2]. Air reduction of an intussusception with a pathologic lead point has not been previously reported. We report a case of an infant with an ileocolic intussusception secondary to a duplication cyst that was successfully reduced with air. The pathologic lead point was recognized at the time of reduction and confirmed with water-soluble contrast. Air is both a diagnostic and therapeutic contrast agent. PMID- 1308667 TI - Coordination of mastication and swallowing. AB - The coordination of mastication, oral transport, and swallowing was examined during intake of solids and liquids in four normal subjects. Videofluorography (VFG) and electromyography (EMG) were recorded simultaneously while subjects consumed barium-impregnated foods. Intramuscular electrodes were inserted in the masseter, suprahyoid, and infrahyoid muscles. Ninety-four swallows were analyzed frame-by-frame for timing of bolus transport, swallowing, and phases of the masticatory gape cycle. Barium entered the pharynx a mean of 1.1 s (range -0.3 to 6.4 s) before swallow onset. This interval varied significantly among foods and was shortest for liquids. A bolus of food reached the valleculae prior to swallow onset in 37% of sequences, but most of the food was in the oral cavity at the onset of swallowing. Nearly all swallows started during the intercuspal (minimum gape) phase of the masticatory cycle. Selected sequences were analyzed further by computer, using an analog-to-digital convertor (for EMG) and frame grabber (for VFG). When subjects chewed solid food, there were loosley linked cycles of jaw and hyoid motion. A preswallow bolus of chewed food was transported from the oral cavity to the oropharynx by protraction (movement forward and upward) of the tongue and hyoid bone. The tongue compressed the food against the palate and squeezed a portion into the pharynx one or more cycles prior to swallowing. This protraction was produced by contraction of the geniohyoid and anterior digastric muscles, and occurred during the intercuspal (minimum gape) and opening phases of the masticatory cycle. The mechanism of preswallow transport was highly similar to the oral phase of swallowing. Alternation of jaw adductor and abductor activity during mastication provided a framework for integration of chewing, transport, and swallowing. PMID- 1308668 TI - The ignoble lie. PMID- 1308669 TI - Heterosexually transmitted human immunodeficiency virus infection among pregnant women in a rural Florida community. AB - BACKGROUND: In the United States, an increasing proportion of women infected with the human immunodeficiency virus (HIV) live in nonmetropolitan areas. Little is known, however, about the risk factors for HIV transmission in women outside large cities. METHODS: We interviewed and tested 1082 (99.8 percent) of 1084 consecutive pregnant women who registered for prenatal care at a public health clinic in western Palm Beach County, Florida. This rural agricultural area of about 36,000 people is known to have a high prevalence of HIV infection. RESULTS: The seroprevalence of HIV was 5.1 percent (52 of 1011 women). Black women who were neither Haitian nor Hispanic had the highest rate of infection (8.3 percent [48 of 575]). Only 4 of 1009 women (0.4 percent) reported ever injecting drugs, and the 4 were HIV-seronegative; however, 14 of 43 users of "crack" cocaine (33 percent) had HIV infection. At prenatal registration, 131 of 983 women (13 percent) tested positive for gonorrhea, chlamydial infection, or syphilis. By multivariate logistic-regression analysis, HIV infection was found to be independently associated with having used crack cocaine (odds ratio, 3.3; P < 0.001), having had more than two sexual partners (odds ratio, 4.6; P < 0.001), being black but neither Hispanic nor Haitian (odds ratio, 11; P < 0.001), having had sexual intercourse with a high-risk partner (odds ratio, 5.6; P < 0.001), and testing positive for syphilis (odds ratio, 3.1; P = 0.015). Nevertheless, 11 of the 52 HIV-infected women (21 percent) reported a total of only two to five sexual partners and no known high-risk partners, had never used crack cocaine, and had no positive tests for sexually transmitted disease. CONCLUSIONS: In the rural community we studied, most of the women with HIV infection acquired it through heterosexual contact. The increasing seroprevalence of HIV and the increasing incidence of syphilis and use of crack cocaine mean that other women may be at similar risk of acquiring heterosexually transmitted HIV infection. PMID- 1308670 TI - On site medical services at major incidents. PMID- 1308671 TI - Prevalence of abdominal aortic aneurysm in the offspring of patients dying from aneurysm rupture. AB - The prevalence of abdominal aortic aneurysm (AAA) is high in the brothers of patients with aneurysm. A genetic component in the development of AAA has, therefore, been postulated. In this study the offspring of patients who had died from AAA rupture were invited to undergo ultrasonography of the abdominal aorta. The attendance rate was 69 per cent. Thirty-nine sons of median age 60 (range 45 75) years and 23 daughters of median age 62 (range 42-80) years were examined. Abdominal aortic dilatation was found in eight men and one woman. The presence of aortic dilatation in these nine cases was not related to age, hypertension, smoking or symptoms of occlusive arterial disease. It is concluded that the sons of those who have died from ruptured AAA constitute a high-risk group for the development of this condition and should be considered for further screening. PMID- 1308672 TI - Can cholangiography be safely abandoned in laparoscopic cholecystectomy? Laparoscopic operative cholangiography: a simple, successful, cost-effective method. PMID- 1308673 TI - Re: Routine radio-imaging in filarial chyluria--is it necessary in developing countries? PMID- 1308674 TI - Non-tuberculous cavitary disease in a west African man with AIDS. PMID- 1308675 TI - Is asthma T-cell mediated? PMID- 1308676 TI - [Immunohistochemistry in the anatomopathologic diagnosis]. AB - In order to determine the value of immunohistochemical staining methods for morphologic diagnosis specimens of 949 cases received at the Immunohistochemistry Laboratory of the Department of Pathology of the Medical School of Botucatu, in the period 1984-1989 were reviewed. All of them were submitted to the immunoperoxidase staining (PAP or ABC). The main morphologic diagnosis was confirmed in 468 cases (49.3%); the definitive diagnosis was made in 244 cases (25.7%) that had only differential diagnosis, and contributory information was provided in 74 cases (7.8%); the immunohistochemical staining was non contributory in 114 cases (12%). It rendered an unsuspected diagnosis in 49 cases (5.2%). The analysis of these cases shows that immunohistochemical methods may provide important and sometimes essential informations for definitive diagnosis. This technique is particularly useful for distinguishing between carcinoma, lymphoma and melanoma. PMID- 1308677 TI - Pathways for fluid loss from the peritoneal cavity. AB - During peritoneal dialysis, fluid is transported out of the peritoneal cavity by lymphatic and nonlymphatic pathways, thereby decreasing net ultrafiltration by 40 50% and reducing small solute clearance by 15-20%. The direct lymphatic pathway consists of the diaphragmatic lymphatics, which directly connect the peritoneal cavity to the bloodstream. The interstitial lymphatic and direct blood entry pathways convey fluid that has been driven into the interstitial space of the tissue surrounding the peritoneal cavity by the increased intraperitoneal pressure, and return it to the bloodstream. Since flow through lymphatic pathways is only a portion of the flow through all pathways, total fluid loss is greater than lymph flow. The best technique for estimating lymph flow is direct measurement by cannulation of lymphatic vessels, a technique that is not clinically feasible. The tracer disappearance technique, which measures the rate at which macromolecules leave the peritoneal cavity, is an indirect measure of fluid loss. The tracer appearance technique, which measures the rate at which macromolecules reach the blood from the peritoneal cavity, slightly overestimates lymph flow because some tracer may enter the bloodstream directly from the tissues. Much of the previous controversy over the contribution of the lymphatic pathways to total fluid loss can be resolved by understanding the differences in what these techniques measure. PMID- 1308678 TI - Studies on lymphatic drainage of the peritoneal cavity in sheep. AB - In the sheep, it is possible to cannulate several of the lymphatics that drain the peritoneal cavity and assess lymphatic drainage of this serous space directly. Indwelling catheters were placed in the caudal mediastinal and thoracic ducts. The right lymph duct could not be cannulated. Lymphatic drainage of the peritoneal cavity based on the movement of 125I-albumin from the cavity into the lymph compartments was not affected by the osmolality of the dialysate but was markedly altered by anesthesia. In addition, lymphatic drainage was assessed from the disappearance of instilled 125I-albumin from the peritoneal cavity and from the appearance of intraperitoneally administered 125I-albumin in the bloodstream and compared with data from the cannulated preparations. Lymph flows derived from tracer movement into the cannulated lymph compartments and from the appearance of tracer in the bloodstream were very similar. However, calculations of lymph flows based on the disappearance of tracer from the peritoneal cavity appeared to overestimate lymphatic drainage. PMID- 1308679 TI - Diaphragmatic lymph vessel drainage of the peritoneal cavity. AB - We have studied the drainage of peritoneal fluid through the diaphragmatic lymph vessels in sheep. To measure the lymphatic flow rate, we cannulated the lymphatic vessels and timed the flow from the cannula. After we infused Escherichia coli endotoxin into awake sheep, the diaphragmatic lymph flow rate increased substantially. However, we found no increase in lymph flow in anesthetized acutely operated sheep. This indicates that studies in anesthetized animals may yield underestimates of diaphragmatic lymph flow. In sheep, many of the diaphragmatic lymph vessels drain to the caudal mediastinal lymph node. We cannulated an efferent vessel from that node in 5 sheep. Several days later we infused 100 ml/kg of Ringer's solution into the abdominal space of each awake sheep. In response, the lymph flow rate increased from 0.15 +/- 0.16 ml/min (mean +/- SD) to 0.50 +/- 0.17 ml/min. Our results are important because they demonstrate that diaphragmatic lymph flow increases substantially after fluid infusions into the abdominal space. PMID- 1308680 TI - Net ultrafiltration in peritoneal dialysis: role of direct fluid absorption into peritoneal tissue. AB - 'Net ultrafiltration' in peritoneal dialysis refers to the difference between the osmotically induced ultrafiltration into the peritoneal cavity and the fluid loss from the cavity during dialysis. Recent research has demonstrated that, during a 3- to 4-hour experimental dialysis, 5-25% of the total fluid loss is via lymphatics and the remaining fluid is absorbed directly into the tissue surrounding the peritoneal cavity. The driving force for this convection into tissue is the hydrostatic pressure gradient between the peritoneal cavity and the tissue, which ranges from 2 to 8 mm Hg during the typical 2-liter dialysis in humans. Because the convection from the cavity occurs during periods of a positive net ultrafiltration, the peritoneum and its underlying tissue cannot be represented as a single membrane but function as a composite of 'tight' and 'loose' membranes. More data on the mechanical properties of the peritoneal tissue space and its response to hydrostatic pressure in the cavity are required before we fully understand fluid transport at the tissue level. PMID- 1308682 TI - Role of lymphatics in peritoneal dialysis. AB - There is a renewed interest in understanding the precise role of lymphatics in the ultrafiltration kinetics during peritoneal dialysis. In the normal state, lymphatics draining the peritoneal cavity are the principal means of removal of intraperitoneal isosmotic fluid and macromolecules. During a hypertonic peritoneal dialysis exchange, after peak intraperitoneal volume is achieved, fluid removal proceeds at an almost linear rate, causing intraperitoneal fluid volume to reduce. The isosmotic fluid removal from the peritoneal cavity could occur through the microcirculatory capillaries or through the lymphatic capillaries draining the peritoneal cavity. Animal and human studies suggest that this fluid loss occurs primarily through lymphatics. The two indirect methods of lymph flow measurements, plasma appearance and peritoneal disappearance of tracer colloid, show conflicting results. Although direct measurement of lymph flow rates through cannulation of mediastinal lymph vessels in animals suggests a significant flow through the lymph channels in response to intraperitoneal fluid instillation, lymph flow modification at the lymph node level may prevent use of this technique to assess the precise role played by lymphatics in fluid kinetics during peritoneal dialysis. By analogy with ascites and by extrapolation from previous studies of drain volumes after infusion of isotonic and hypertonic solutions, the average daily lymph absorption rate during CAPD may be predicted to be at least 1 liter per day. PMID- 1308681 TI - Lymphatic and nonlymphatic pathways of peritoneal absorption in mice: physiology versus pathology. AB - In conjunction with our studies of the pathogenesis of malignant ascites formation, we have analyzed the transperitoneal transport of macromolecules in mice. In this review, I summarize our experimental results concerning the influx (transport from the blood to the peritoneal cavity) and efflux (transport from the peritoneal cavity to the blood) of a number of different tracers [fluorescein labeled dextrans (FITC-D), 51Cr-RBC, 125I-HSA, and 125I-fibrinogen]. We examined tracer transport in ascites tumor-bearing animals as a function of tumor growth and compared our results with transport properties obtained in normal awake mice and in mice that had received an intraperitoneal injection of a solution of 5% bovine serum albumin to simulate the protein-rich fluid accumulation associated with ascites tumor growth in the peritoneum. Our results indicate that both increased influx as well as impaired efflux are required to initiate and maintain tumor ascites fluid accumulation. To test the hypothesis that increased influx reflected increased vascular permeability, we monitored transport of intravenously injected FITC-D tracers (FITC-D) into the peritoneal cavity by fluorescence microscopy. To investigate the mechanisms involved in the decreased efflux, we determined tracer efflux rates both as the rate of appearance in the blood and as the rate of disappearance from the peritoneal cavity. We compared these transport properties for both soluble as well as particulate tracers. Our results indicate that there are additional routes of egress available to soluble macromolecules not available to particulate tracers such as 51Cr-RBC, and that in ascites tumor-bearing animals, the lymphatic pathway is shut off rather rapidly as judged by the decreased rate of 51Cr-RBC removal. By fluorescence microscopy we observed the interstitial tissue uptake of intraperitoneally injected soluble macromolecules (FITC-D) in the parietal peritoneal wall, particularly in animals with an increased intraperitoneal pressure, thereby confirming additional nonlymphatic pathways of peritoneal absorption in mice. Finally, we used the particulate tracer 51Cr-RBC to estimate the peritoneal lymphatic drainage rate, yielding a value of 1.6 microliters/min in normal awake mice based on the rate of tracer disappearance from the peritoneum. PMID- 1308683 TI - Lymphatic versus nonlymphatic fluid absorption from the peritoneal cavity as related to the peritoneal ultrafiltration capacity and sieving properties. AB - In this article we discuss the role of capillary fluid absorption via Starling mechanisms (the transcapillary hydrostatic pressure gradient opposed by the colloid osmotic pressure gradient as multiplied by the capillary UF coefficient) vs. lymphatic fluid absorption as determinants of the total fluid loss from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). We also mention that, under nonsteady state conditions, there is in addition some net absorption of fluid into the interstitium of tissues surrounding the peritoneal cavity. Support for the contention that nonlymphatic fluid absorption directly into the capillaries is the major mode of fluid transport from the peritoneal cavity to the blood is given by measurements of the peritoneal-to blood clearance of tracer albumin (or other proteins). Such measurements yield clearance values of the order of 0.2-0.3 ml/min in CAPD. This represents only about 20% of the total peritoneal fluid loss rate (1.2-1.3 ml/min) in ordinary CAPD dwells. Indirect support for a relatively low lymph flow is also derived from capillary physiology. Like continuous capillary walls, the peritoneal membrane shows a bimodal selectivity towards molecules of graded molecular size. Thus, small solute transport can be described as occurring by diffusion through numerous 'small' (approximately 50 A radius) pores, whereas large solute transport is consistent with blood-peritoneal convection through smaller numbers of 'large' (radius approximately 250 A) pores. Furthermore, peritoneal sieving data are compatible with the notion that large crystalloid osmotic pressure gradients cause fluid flow through a water-exclusive ('ultra-small' pore) pathway. A three-pore model of peritoneal selectivity can explain why small solute sieving coefficients are only 0.5-0.6, even though small solute reflection coefficients are close to zero. Another important implication of the three-pore concept is that the peritoneal UF-coefficient is much higher than previously thought, emphasizing the role of capillary absorption in the fluid loss from the peritoneal cavity in CAPD. It is concluded that fluid loss from the peritoneal cavity is dominated by capillary fluid absorption. Hence, lymphatic absorption accounts for just a small fraction of the peritoneal-to-blood absorption of fluid in peritoneal dialysis. PMID- 1308684 TI - Intraperitoneal fluid fluxes analyzed according to the 'three-pore' model in individual patients on CAPD. AB - Individual CAPD patients have markedly different characteristics of their peritoneal membranes, making it desirable to measure the transport rates of each individual in order to ensure adequate dialysis. An analytical tool has been developed based on the three-pore concept of microvascular exchange, whereby it is possible to differentiate among possible causes for disturbances in PD. A so called loss of ultrafiltration during PD can result from two different causes. First, an increased total pore cross-sectional area available for diffusion (or A0/delta x) can cause increased transport of glucose to blood and hence diminish the osmotic gradient such that a net filtration turns to net reabsorption of fluid from the abdominal cavity to the blood. Secondly, fluid loss can be due to a high lymph flow (>> 0.3 ml/min/1.73 m2). PMID- 1308685 TI - Net fluid absorption under membrane transport models of peritoneal dialysis. AB - The effect of oncotic pressure and lymphatic flow on intraperitoneal dialysate volumes in peritoneal dialysis is investigated under each of two membrane transport models: one assuming a homogeneous single-pore membrane and the other a heteroporous three-pore membrane. In both cases, solute and fluid removal are assumed to occur via a mass transport model in which the peritoneum acts like a synthetic membrane separating two well-mixed compartments (body and dialysate). The homoporous mass transport model of Pyle and Popovich and the three-pore model of Rippe et al., although conceptually different, are shown to be equivalent mathematically. This feature allows one to apply the analytical solutions of Vonesh et al. to either model. It also enables one to apply parameter estimates from one model to another; for example, one can apply the lumped sum reflection coefficients of the three-pore model to a homoporous membrane model. A comparison is made between the use of empirically estimated rejection coefficients computed under the homoporous membrane model of Pyle and Popovich versus lumped-sum reflection coefficients calculated in accordance with the three-pore model of Rippe et al. The two models predict similar drain volumes provided the exchange is conducted using glucose as the osmotic agent. However, one does see a significantly different contribution of protein oncotic pressure and lymphatic drainage to fluid absorption under the two sets of osmotic reflection coefficients. Moreover, for a simulated exchange employing an osmotic agent with a molecular weight of 20,000 daltons, the use of reflection coefficients calculated under the three-pore model yields net ultrafiltration values which are more consistent and physiological than results obtained using the empirically estimated rejection coefficients. Since estimates of 'lymphatic flow' will vary according to the quantity and quality of input parameter values (i.e., hydrostatic pressure, protein concentrations, osmotic reflection coefficients), it would be better to label these estimates as the sum of lymphatic and unmodeled net fluid absorption. PMID- 1308686 TI - Evaluation of peritoneal membrane pore models. AB - Pore models of peritoneal fluid and solute transport are reviewed and critiqued. Although several pore models of the peritoneal membrane have been previously formulated, a model containing three distinct pore sizes is required to accurately simulate both the molecular size dependence of solute transport and the time dependence of fluid transport during peritoneal dialysis in man. Nevertheless, certain observations from peritoneal dialysis experiments using animals do not agree with predictions from the three-pore model. These discrepancies suggest that the three-pore model of peritoneal transport based exclusively on capillary physiology is incomplete. Moreover, our inability to accurately estimate peritoneal reflection coefficients for small osmotic solutes questions whether lymph flow rates from the peritoneal cavity calculated using the three-pore model are reliable. Further experimental and theoretical studies are needed to obtain a better understanding of peritoneal transport physiology. PMID- 1308687 TI - Current trends in the management of invasive bladder cancer. AB - In muscle-invasive bladder cancer, attempts at cure have traditionally involved radical local treatment by either radiotherapy or ablative surgery. However, these treatments have been associated with a high morbidity and have failed to address the problem of subsequent metastatic disease, to which many patients eventually succumb (often within the first 3 years after treatment). Modern imaging techniques have led to much improved staging information, allowing careful selection of patients suitable for radical "curative" treatment; at the same time, patients identified as already having metastatic disease may be spared major surgery that is unlikely to influence the outcome of their disease. Reconstructive surgical techniques are beginning to transform the quality of life for patients offered radical surgery, by avoiding the need for traditional urinary diversion. In addition, the use of neo-adjuvant chemotherapy combined with radical local treatment addresses the problem of micrometastases at diagnosis and offers the prospect of improved survival, although the results of clinical trials are awaited to evaluate this further. Future advances in treatment may be expected to occur as our understanding of the biology of bladder cancer increases. Of particular value will be predictive information about the invasive potential of initially superficial tumours, so that these cases may be targeted for "aggressive" treatment from the outset. PMID- 1308688 TI - Current trends in the management of localised prostate cancer. AB - The incidence of prostate cancer in the UK is increasing, and the disease is being detected more often in younger patients (e.g. from routine PSA measurement during health-care screening). Left untreated, a significant proportion of patients will undergo progression of their disease locally and/or develop metastases. Modern imaging techniques have greatly aided the assessment of early prostatic cancer, enabling both accurate assessment of the primary tumour and giving valuable information regarding lymph node metastases. PSA measurements are also extremely helpful, and this has replaced acid phosphatase as a marker for prostatic malignancy. Controversy still remains, however, over the best form of management. Radical prostatectomy undoubtedly produces the best results in the literature, but the patients are highly selected (e.g. those with nodal metastases are excluded) and some patients with well differentiated tumours may have been over-treated, as they may have been expected to do well with surveillance alone. Full clinical trials are required in identically staged patients to assess the relative merits of surveillance, radiotherapy and surgery, and this should now be possible with recent advances in imaging techniques. PMID- 1308689 TI - The role of ultrasound in the management of scrotal disorders. PMID- 1308690 TI - Incontinence in the elderly. PMID- 1308692 TI - Neuroborreliosis in South Wales. PMID- 1308691 TI - Extra pyramidal side effects associated with paroxetine. AB - A 29-year-old man admitted to a psychiatric unit was successfully treated for a paranoid psychosis with trifluoperazine. Following reduction of neuroleptic dosage and addition of paroxetine he developed severe extra-pyramidal side effects. These remitted after withdrawal of medication and did not recur following recommencement of trifluoperazine. This is the first report of such a side effect associated with paroxetine use in man. PMID- 1308693 TI - Occupational therapy--does the doctor know? PMID- 1308694 TI - Perception and awareness of phonemes in phonologically impaired children. AB - Fourteen phonologically impaired children and 14 normally speaking controls were given tests of speech discrimination, in which they had to distinguish between similar phonemes, and tasks of rhyme judgement and matching words on the basis of their initial phoneme, which require the child to identify the same sounds across differing word contexts. Compared to the control group, children with phonological impairment were poor on the phoneme discrimination tasks, but there was wide variation in performance and seven of these children scored near ceiling levels. All children showed some ability to discriminate contrasts they could not produce. Substantial deficits were found in the ability of phonologically impaired children to identify phoneme constancy across differing word contexts. It is difficult to explain such findings in terms of impaired auditory discrimination. Results are discussed in relation to normal phonological development, and it is suggested that phonologically impaired children do not progress to the stage of analysing words at the level of the phoneme. PMID- 1308695 TI - The effects of speech and language therapy for a case of dysarthria associated with Parkinson's disease. AB - We report the results of a single-subject multiple baseline across behaviours experiment of a 74-year-old woman presenting with Parkinson's disease. Her speech was typical of a hypokinetic dysarthria. The main features of her dysarthric speech were: a restriction in the modulation of fundamental frequency, an inappropriate pitch level and a rate disturbance. Three measures of prosody were operationally defined as follows: (1) linguistic modulation of fundamental frequency, (2) mean fundamental frequency and (3) rate. Treatment focused on ameliorating these aspects employing a multiple baseline design. Measures during and post-therapy documented improvement for each of these three aspects of prosody. Independent judges were also more capable of understanding her speech and her speech prosody after therapy. Upon follow-up measures 10 weeks later, most of the improvement was maintained. PMID- 1308696 TI - Characteristics of children with specific language impairment attending language units. AB - The characteristics of children with specific language impairment (SLI) attending four language units in the north-west of England are examined. The present study involved 15 children with SLI and two sets of control groups: a same-age group and an MLU-matched group (MLU = mean length of utterance). Results are discussed in terms of the following questions: Do children with SLI attending language units fit the classic definition of SLI? Can children with SLI be categorised as having expressive versus receptive language problems? What other aspects of educational attainment such as reading, maths and science are affected by SLI? The paper ends with implications for future research. PMID- 1308697 TI - Frozen phonology thawed: the analysis and remediation of a developmental disorder of real word phonology. AB - A 5-year-old boy presented with very deviant phonological production, as well as some delay in acquisition of vocabulary for comprehension. Investigations showed that, in contrast to his very limited phonological system in word production and naming, he was able to repeat a variety of non-words with reasonable accuracy using a variety of syllable structures. A period of therapy aimed at improving his phonological segmentation skills resulted in dramatic improvement in real word production to the same level that he showed with non-words. This improvement was specific to the domain of treatment--real word phonology--demonstrating that the effects were a result of the therapy regimen. The reasons for this dissociation between the phonology of real words and non-words are discussed. It is concluded that the child's pattern of performance is incompatible with theories which assume that a single phonological representation is used both for word recognition and for output. His deficit appears to lie in a failure to update the underlying phonological representations used to drive spoken output as his phonological abilities develop--his lexical phonology was 'frozen'. PMID- 1308698 TI - Amebiasis: a problem solved. What now? Bernardo Sepulveda Memorial lecture. PMID- 1308700 TI - Ferruginous bodies in cases with occupational and non-occupational exposure to inorganic dusts. A study with 40 matched cases. AB - In this study we evaluated the usefulness of ferruginous bodies (FB) quantification in lung digest and histologic sections from 40 patients with a history of exposure to inorganic dusts. The patients were matched with 40 cases without occupational exposure. The samples of peripheral lung tissue were digested and all FB were quantified. Lung sections were also evaluated in order to confirm the presence of FB. The concentrations of FB in the patients were higher than the controls (Wilcoxon test, p < 0.001). The patients group showed a median concentration of 194.5 FB/g of dry lung tissue (FB/g) vs. 34.0 FB/g in the controls. Seventy percent of the patients had more than 100 FB/g vs. 27.5% in the controls cases. Pneumoconiosis was diagnosed in 19 patients, 17 had FB/g above 100 and only 4 were positive to FB in lung sections. We can conclude that lung digest and FB counts help to confirm exposures to inorganic dusts above the background values found in the general population. FB counts can help when the clinical file does not confirm the exposure. PMID- 1308699 TI - Effects of avocado as a source of monounsaturated fatty acids on plasma lipid levels. AB - To examine the effects of avocado on plasma lipid concentrations, a three-diet trial involving 16 healthy volunteers was carried out. A diet rich in monounsaturated fatty acids using avocado as their major source (30% of the total energy was consumed as fat: 75% of the total fat from the avocado), with restriction of saturated fats and less than 300 mg of cholesterol per day was evaluated. Subjects also were in a free-diet period with the addition of the same amount of avocado. Finally, volunteers received a low-saturated fat diet without avocado. The first and third diets were designed to simulate a usual diet and volunteers carried on their normal activities during the trial, only the three daily meals were eaten in our clinical unit. Diets lasted 2 weeks and they were assigned in a randomized order. In both rich-monounsaturated fat (RMF) and low saturated fat (LSF) diets, there were similar reductions in the plasma total cholesterol and low-density lipoprotein cholesterol levels. The levels of high density lipoprotein cholesterol significantly decreased (p < 0.05) after 2 weeks of the LSF and free monounsaturated-enriched (FME) diets. The plasma triacyglycerol levels lessened after RMF and FME diets, while LSF diet increased them. In total cholesterol and in low-lipoprotein cholesterol levels, there were statistically significant differences between the FME and the LSF diet periods. Avocado is an excellent source of monounsaturated fatty acid in diets designed to avoid hyperlipidemia without the undesirable effects of low-saturated fat diets on HDL-cholesterol and triacylglycerol concentrations. PMID- 1308701 TI - Isolated congenital heart defects in first degree relatives of 185 affected children. Prospective study in Mexico City. AB - Parents (n = 355) and siblings (n = 313) of 185 index cases (IC) with congenital heart disease (CHD) were cardiologically evaluated. In the consecutive sample (2 years) Mendelian and chromosome syndromes were excluded. Four patients and nine siblings had CHD. The frequency of affection in siblings was 2.6% (8 in 313 siblings). All affected relatives are under medical care at the Centro Medico Nacional Siglo XXI, IMSS. In 10 of the 12 affected relatives found, the type of CHD was discordant from that of the IC. Discordance was found also in 9 of 36 IC with two or more CHD. An interpretation is given: if the mutated gene(s) has its effect in early embryological stages, affected relatives may have any type of CHD, but if the alteration occurs later, concordance is expected to be found. This model contributes also in explaining the remarkable genetic heterogeneity that exists in CHD. PMID- 1308702 TI - Local recurrence of rectal adenocarcinoma following preoperative radiation therapy and surgery. AB - An important therapeutic endpoint of the surgical treatment of rectal adenocarcinoma is to obtain local control. In an attempt to enhance this goal, we started a regimen of treatment consisting of preoperative radiation therapy (PRT), 45 Gy in 5 weeks, followed by surgery 4-6 weeks after termination of the PRT. Depending on the local characteristics of the tumor, either an abdominoperineal resection (APR), a posterior pelvic exenteration (PPE), and a total pelvic exenteration (TPE) were performed. All patients found with distant metastasis were excluded from this study. There were 66 patients: 40 males and 26 females. Fifty six underwent an APR, six a PPE, and four a TPE. Their median age was 56 years. Major complications were intraoperative bleeding (15%); perineal wound infection (21%); abdominal wound infection (9%). Five patients (7.5%) died within 30 days of surgery; two after APR, two after PPE and one after TPE. Median follow-up is 60 months. The overall local recurrence rate is 9.8%. Recurrences related to the Astler-Coller modification of Dukes' stage were 0/21 in A or B1, but 6/40 (15%) when the stages were B2, B3, C1, C2 and C3. In conclusion, we found this treatment approach effective in obtaining local control of the rectal adenocarcinoma and comparable to the results of other series. However, it was associated with significant morbidity and mortality. PMID- 1308703 TI - Changes of energetic value and protein level of rumen content in sheep fed with stuff with livex and blood meal supplementation. AB - The aim of studies was to determine the influence of Wroclaw product from blood- brown, dried livex (modified by whey) and blood meal, which were added to sheep forage, on energetic value and protein, also volatile fatty acids (VFA) levels in rumen content of these animals. The samples of rumen content for determination of the three parameters mentioned above were taken 2.5 hrs after finished morning feeding. The addition of livex and blood meal to forage was 2%. When two non conventional diet supplements were used in vivo, there was observed significant inhibitory influence of livex on methane level among rumen gases, amounting to 38.9% in sheep and increase in protein amount of about 25.92% (for blood meal these values were: 5.6% and 7.4%, respectively). In connection with that, energy of rumen content was higher by about 22.22% in group of sheep fed with stuff with livex addition and by about 7.41% in group fed forage with blood meal addition. The using of livex as an addition to fodder caused increase of the rumen fermentation efficiency and also regulation of non-glucogenic ratio of volatile fatty acids. PMID- 1308704 TI - Investigation of usefulness of electroreticulograms obtained from the sheep body surface in estimation of reticulum electrical activity. AB - The experiments were carried out on 3 sheep with one pair of platinum electrodes chronically implanted in the reticulum wall. The reticulum action potentials were recorded simultaneously from the body surface (using the needle electrodes placed subcutaneously) and from the implanted electrodes using an electroencephalograph Reega XVI Duplex TR. It was found that the two- or three-phase deflections on the electroreticulograms obtained from the body surface were exactly correlated with the series of potential spikes on the records from the implanted electrodes. The number of phases in each deflection was equal to the number of the series of potential spikes during the reticulum excitation. During the reticulum hypotony the decrease in action potentials was observed. That is why we were not able to record the electrical activity from the body surface, while it was still possible to record electroreticulograms from the implanted electrodes. PMID- 1308705 TI - The effect of calcium ions on the intensity of peroxidation processes and the severity of ethanol-induced injury to the rat's gastric mucosa. AB - The effects of verapamil (Isoptin Knoll) and calcium glubionate (Calcium Polfa) were studied on the generation of free radicals and activity of anti-oxidant enzymes in rat's gastric mucosa following the oral administration of 50% ethyl alcohol. Ethanol in this concentration caused injury to gastric mucosa as well increased the levels of peroxidation products (malonyl dialdehyde, hydroperoxides and conjugated dienes); at the same time a decreased enzyme activity was observed (superoxide dismutase, peroxidase, glutathione peroxidase, glutathione reductase, catalase). Verapamil administered before ethanol increased the ulcerogenic activity of alcohol, increased the activity of the studied antioxidant enzymes (except catalase) and caused the decrease in the levels of peroxidation products in gastric mucosa. Calcium glubionate increased the enzyme activity and showed some protective effect on gastric mucosa. PMID- 1308706 TI - The role of selected biochemical components of equine seminal plasma in determining suitability for deep-freezing. AB - Experiments conducted on the freezability of 400 ejaculates collected from 64 stallions demonstrate the possibility of predicting the semen's ability to withstand the freezing/thawing process. If the sperm concentration, AspAT activity and total protein content in the seminal plasma of raw ejaculates are determined before freezing, the effects of freezing may be forecast in about 80% of the ejaculates. PMID- 1308707 TI - Cytoarchitecture of the paracervical ganglion (Frankenhauser) of pig. AB - Employing different histochemical methods, the morphology of the paracervical (Frankenhauser) ganglion is described in sexually immature pigs. The bilateral ganglion of an elongated shape is situated on both sides of the ventro-lateral surface of the cervical and vaginal wall in the proximity of their junction, lying under the serous membrane. Three main groups of cells have been identified and described, namely: principal cells, SIF cells and satellite cells. It has been determined that some of these cells contain noradrenaline, others, however, acetylcholinesterase. The paracervical ganglion is most likely the main source of supplying the vagina, cervix, uterine corpus and partly its horns with postganglionic adrenergic fibers. PMID- 1308708 TI - The influence of Ambroxol on peroxidative processes in lung and plasma in dogs after pulmonectomy. AB - The purpose of the studies was to determine the effect of Ambroxol on the activity of antioxidant enzymes and on the glutathione level as well as the intensity of the peroxidative processes in the lung tissue, alveolar macrophages and plasma in dogs after unilateral pulmonectomy. On the 2nd and 6th day after the surgery the activity of antioxidant enzymes and the glutathione level were studied in the remaining lung. The levels of the lipid peroxidation products were determined in the analogous system. In both examined groups the increase in the antioxidant enzyme activity and the lipid peroxidation product levels was observed in the remaining lung after the surgery. In Ambroxol-treated animals the statistically significant increase in the antioxidant enzyme activity was noted while the intensity of peroxidative processes was found to be lower. This fact may suggest that Ambroxol stimulates the resistance of the lung tissue to the free radical activity and inhibits the lung peroxidative processes in dogs after pulmonectomy. PMID- 1308709 TI - Seasonal variations of antipyrine pharmacokinetics parameters in calves. AB - In the experiment the values of parameters of antipyrine kinetics were defined (Vd - volume of distribution, t0.5 - half-life, CA - metabolic clearance) in calves in January, April, July and October 1986 and in January and July 1987. Statistically significant increase of distribution volume and increase of hepatic antipyrine clearance were recorded, as well as significant shortening of half life of this substance in the organism of tested animals in summer 1986 and 1987, compared with the remaining seasons of the year. Antipyrine pharmacokinetics in winter, spring, autumn 1986 and winter 1986/87 did not differ significantly. PMID- 1308710 TI - Effect of LH and prolactin on steroid secretion by perifused luteal tissue from pregnant gilts with induced hypoprolactinemia or after passive immunoneutralization of LH. AB - The study was performed using luteal tissue obtained from 24 pregnant gilts. Group I was treated with bromocriptine (BR) from 37th to 42nd day of gestation. Group II was treated with homologous anti-pLH serum from 37th to 42nd day of pregnancy. Group III was given BR from 67th to 72nd day of gestation. Group IV received anti-pLH serum from 67th to 72nd day of pregnancy. The effect of exogenous LH or prolactin (100 ng/ml) on secretion of progesterone (P4) and estradiol (E2) by luteal tissue was studied using perifusion technique. Prolactin caused a significant (P < 0.05) increase in P4 secretion by luteal tissue from gilts in groups I and IV. Both LH and prolactin decreased (P < 0.05) estradiol secretion by luteal tissue obtained from gilts from group IV. Luteinizing hormone stimulated (P < 0.05) P4 and E2 secretion by luteal tissue from gilts from groups IV and II, respectively. The results demonstrate that both LH and prolactin have a regulatory role in steroid secretion by luteal tissue of gilts in the mid- and late periods of pregnancy. PMID- 1308711 TI - Pharmacokinetics of antipyrine in calves during first 35 days of life. AB - The experiment was carried out on 10 bull-calves of black-white breed, aged 2-35 days. The following parameters of antipyrine pharmacokinetics were determined: Vd - volume of distribution, t0.5 - biological half-life, CA - metabolic clearance. It has been shown statistically that the volume of antipyrine distribution (expressed in 1/kg) was significantly decreasing with age of examined animals. The antipyrine half-life proved to be the longest on the 20th day of calves' life and the shortest on the 10th and 30th day. The maximum values of metabolic clearance of antipyrine were observed in calves aged 10 days and the minimum ones in animals aged 20 days. In the cases of t0.5 and CA a tendency to changes of values of these parameters of antipyrine pharmacokinetics in 10 days periods was observed. PMID- 1308712 TI - The changes in bile flow and its composition in sheep following liver damage by carbon tetrachloride. AB - Sheep were prepared surgically in a manner permitting the measurement of bile flow by preserving its enterohepatic circulation. Carbon tetrachloride (CCl4) was administered intraruminally in a dose 0.5 ml/kg b.w. After CCl4 administration a decrease in bile flow and bile acid excretion was observed. The decrease in bile flow observed after CCl4 administration was lower than the decrease in bile acid output. Thus it can be suggested that in this condition the effects of bile acid output on the bile secretion can be partially abolished and maintaining of relatively high bile flow is connected with an increase in the bile acid independent bile flow. The increase of the bilirubin concentration in bile was observed after acute liver damage by carbon tetrachloride. PMID- 1308713 TI - Prospective endoscopic study of duodenal ulcer in Zimbabwean Blacks. AB - One thousand seven hundred and fourteen Black Zimbabwean patients underwent upper gastrointestinal endoscopy. Demographic details of the patients were analysed. A randomly chosen cohort of 50 patients with duodenal ulceration was compared to age and sex matched controls regarding lifestyle and H. pylori infection. Five hundred and sixteen patients had active duodenal ulcers, giving a crude prevalence rate of ulceration of 456 per 100,000 new hospital cases. There is a difference from the disease in Western countries in several respects. The incidence appears to be increasing in Zimbabwe. There was no significant difference between ulcer patients and controls in their association with alcohol consumption, cigarette smoking, urban residence and salicylate ingestion (p > 0.1), Ulceration was most strongly associated with H pylori gastritis compared to control (p < 0.001). Duodenal ulceration was most prevalent in the 21 to 30 year age group. The overall male to female ratio was 4.7:1. A significant proportion of patients had persistence of ulceration after a standard course of Cimetidine. Pain did not always correlate with presence or absence of ulcers. PMID- 1308714 TI - Booked and unbooked mothers delivering at Harare Maternity Hospital, Zimbabwe: a comparison of maternal characteristics and foetal outcome. AB - This study was prompted by the poor maternal and foetal outcome at Harare Maternity Hospital, Zimbabwe, in unbooked mothers compared to women who had booked for antenatal care. Comparison was made of 195 recently delivered unbooked mothers with 196 booked mothers. Unbooked mothers were significantly more likely to be younger, of lower parity, be single, have lower socio-economic status, live in or migrate from rural areas, be uneducated and have an unwanted pregnancy. Their infants were significantly more likely to preterm and/or of low birth weight and had a higher perinatal mortality. The major reasons cited by the women for not booking were lack of money and delivery occurring before the intended time of booking. Discussion focuses on how to improve outcome in unbooked mothers. PMID- 1308715 TI - Some pharmacological actions of aloe extracts and Cassia abbreviata on rats and mice. AB - The effects of crude extracts (500 mg/kg IP and 500-1000 mg/kg PO) of three species of aloes and Cassia abbreviata in rats and mice were studied, particularly as regards their abortifacient actions. The LD50 values were as follows: A. globuligemma < 250 mg/kg IP; A.chabaudii 250-500 mg/kg IP; A. cryptopoda > 1500 mg/kg IP and C.abbreviata 500-750 mg/kg IP. Thus the most toxic was A.globuligemma. Their most visibly striking toxic effects in rats were CNS depression, and post mortem investigations showed widespread haemorrhagic lesions. Administration of the aloes and A.abbreviata to pregnant mice and rats did not cause expulsion or resorption of the foetuses. Several rats died within 36 hours of injection of A.chabaudii and A.globuligemma, but even in these rats there was no expulsion or resorption of the foetuses. Rats which survived the treatment delivered normal sized, healthy litters at term. It is suggested that neither the aloe species test nor C.abbreviata possess abortifacient activity at doses which are not toxic to the animals. PMID- 1308717 TI - Molar or mass? PMID- 1308716 TI - Correlations between weights of newborn babies, placental parameters and gestational age. AB - The relationships between foetal weights, placental parameters and gestational ages were studied in 200 placentae. In addition to confirming that foetal weight, placental weight and gestational age correlated, the results showed that baby weight, placental weight, placental surface area correlate to the length of cord and that the length of cord correlates to gestational age (p < 0.05). These correlations are reported for the first time and are difficult to explain. It is recommended to establish birthweight standards in order to assess intra-uterine growth retardation, and to re-examine the correlations reported here through prospective studies as they might be relevant clinically and provide important clues on morbidity prospects of an individual during postnatal life. PMID- 1308718 TI - Intermittent peritoneal dialysis in the management of refractory heart failure. PMID- 1308719 TI - Diminishing medical population (and other medical professions) PMID- 1308720 TI - Long-term results of tricuspid annuloplasty according to DeVega. AB - The long-term results on 36 patients undergoing tricuspid annuloplasty according to DeVega over the years 1981-1990 were analyzed. All had mitral valve replacement or repair in addition to the above procedure. Moreover, three patients had aortic valve replacement while aortocoronary bypass and interatrial septal defect closure was performed in two cases each. Duration of follow-up ranged between 6 to 72 months (mean 36 months). All patients were examined by echocardiography. Significant tricuspid regurgitation was found in three of the patients operated on, manifest clinical signs of the condition were present in one female patient only. Functional evaluation reassigned 72% of the operated patients from Class III and IV to Class I and II, and apparent subjective improvement was reported by 81% of patients. The analysis showed that indication of patients for simultaneous management of tricuspid regurgitation associated with mitral valve disease is justified, and that the surgical technique employed is appropriate. PMID- 1308721 TI - Carotid artery involvement in patients with ischaemic heart disease prior to myocardial revascularization. AB - A carotid arterial bed with sclerotic lesions in patients with ischaemic heart disease before myocardial revascularization in extracorporeal circulation raises the risk of development of serious irreversible dysfunction of the central nervous system. The authors report on the results of ultrasound examination of the carotid arteries in 284 patients, hospitalized at the Department of Cardiac Surgery of University Hospital at Hradec Kralove prior to myocardial revascularization between 1986-1990. Based on their results, and in agreement with data of the literature, the authors recommend to perform non-invasive examination of the carotid arterial bed in all patients prior to myocardial revascularization and, based on the results of the examination, to follow a strictly individualized investigational and therapeutic algorithm. PMID- 1308722 TI - A comparison of the protective effect of a modified StTH solution and HTK-B on the energy and functional status of the isolated rat heart. AB - Using a model of the isolated beating rat heart, the authors compared the protective effect of St. Thomas Hospital cardioplegic solution enriched with glucose and mannitol (StTH-M) and Bretschneider solution (HTK-B). Results showed that, during 120-minute global ischaemia in cardioplegia, StTH-M was able to maintain levels of high-energy phosphates comparable with those found in a group of hearts perfused with HTK-B at 20 degrees C only when the temperature had been decreased to 12-15 degrees C. Under these conditions, repair of metabolic and functional parameters during post-ischaemic perfusion was also similar in both groups. PMID- 1308723 TI - Urinary albumin excretion in patients with renovascular hypertension. AB - Twenty-four hour urinary excretion of albumin (UEalb), IgG and beta-2 microglobulin was investigated at a 3 hour-interval in a control group (C) of healthy subjects, in 30 patients with renovascular hypertension (RVH), and in 16 patients with essential hypertension (EH). Mean UEalb in RVH was significantly higher than in C. A significant direct correlation was demonstrated between diastolic blood pressure and UEalb (p < 0.01). Microalbuminuria (MA) > or = 30 micrograms.min-1 was found in about 18% of RVH patients; it was higher than 16.7 micrograms.min-1 in approx. 31%. These results did not substantially differ from those obtained in patients with EH. The cause for increased UEalb in hypertensive patients may be functional, haemodynamic changes, or structural ones. In either case, MA indicates renal injury, and these patients should be given increased attention when monitoring their blood pressure and when selecting antihypertensive drugs. PMID- 1308724 TI - Follow-up of outpatients with essential hypertension. A comparison of three methods of blood pressure measurement. AB - Compared with conventional, routine blood pressure measurement in the outpatient department of a hospital, 24-hour blood pressure monitoring provides more comprehensive information about blood pressure values in day-to-day life of the hypertensive patient. The hospital setting with all its stimuli affects the hypertensive patients so that their values will be statistically significantly higher compared with normal ones. Recent years have seen the introduction into clinical practice of self-monitoring by the patients themselves. Comparison of these three methods for blood pressure measurements revealed that self-monitoring may provide fairly accurate values comparable with those obtained by the "standard method", i.e., 24-hour monitoring. In view of the low variability of the mean value of blood pressure over a period of several days, self-monitoring can be employed in groups of selected outpatients on long-term follow-up. PMID- 1308725 TI - Metabolic effects of enalapril in the treatment of essential hypertension. AB - In an open two-month study with an initial placebo period, the effect of enalapril on glucose tolerance, insulin (IRI) sensitivity and lipid profile was evaluated in 20 patients with mild to moderate essential hypertension. The following results were obtained: 1. Enalapril produced a favourable effect of blood pressure both in monotherapy and if combined with a diuretic. 2. Therapy did not lead to significant differences in blood glucose, IRI or IRI/glucose increase at 1 or 2 hours of oral glucose tolerance test either in patients with monotherapy or combination therapy, and with normal or disturbed glucose tolerance, respectively. 3. Serum lipids (total and HDL-cholesterol and triglycerides) did not change significantly in any group of patients. PMID- 1308726 TI - The problem of chronic left ventricular asynergy. PMID- 1308727 TI - Prognostic value of body mass index in the development of cardiovascular diseases among Kaunas male population. AB - The paper presents the results of a primary medical examination and of a prospective, on the average 14-year follow-up study of the male population of Kaunas aged 45-59 years (n = 2452). The prevalence of overweight, according to the WHO criteria, was 48.7%, that of obesity 20.5%. With increasing body mass index (BMI) there occurred a statistically significant increase of main risk factors of ischaemic heart disease (IHD) and of IHD itself. The results of the prospective study showed a U-shaped relationship between BMI and mortality from all cardiovascular diseases, and a J-shaped relationship between BMI and mortality from IHD and morbidity of acute myocardial infarction, respectively. The same relationship held true even after standardization of the level of all other risk factors using the multiple logistic function. Thus, the overweight was confirmed as an independent IHD risk factor in the given population. PMID- 1308728 TI - A long history of the left main coronary artery occlusion. AB - The case of a 70-year-old woman with severe angina pectoris for 12 years and occlusion of the left main coronary artery is presented. The reasons for this long history seemed to be adequate collateral circulation, hibernating myocardium, as well as incredible patience of the patient. PMID- 1308729 TI - Circulating endothelial cells in surgical patients. AB - The circulating endothelial cells (CEC) in healthy volunteers and surgical patients before and after operations were counted. The results showed that CEC counts of the patients were much higher than those of the volunteers. After operation, however, patients' CEC counts returned to control levels. It is suggested that detection of CEC may be useful for quantitatively evaluation of the injury to blood vessels in surgical patients. The operation may not only remove the source of injury, it also eliminates the injured microvascular bed which may be important to maintain homeostasis. Another possible interpretation of the results may be related to time lag and mental stress. PMID- 1308730 TI - Age-related changes in the levels of IgG, IgM and IgA antibodies to type I collagen in the sera of normal human subjects. AB - Serum samples from healthy subjects of different ages (within the age range of 1 75 years) were tested for the presence of anti-type I collagen (anti-CI) IgG, IgM and IgA by enzyme-linked immunosorbent assay (ELISA). All the tested sera showed anti-CI antibodies from the three immunoglobulin classes with the following age related regularities: 1. Anti-CI IgG and IgM showed statistically non-significant changes up to the age of 60 decreasing thereafter. 2. Anti-Ci IgA changed negligibly up to the age of 40 increasing with age thereafter. The established age-related changes in the levels of anti-CI antibodies may serve as a basis for future studies of normal and pathological turnover of type I collagen. PMID- 1308731 TI - Pulse repetition rate and duration affect the responses of bat auditory cortical neurons. AB - Under free field stimulation conditions, we studied the effect of pulse repetition rate and duration on the responses of auditory cortical neurons of the big brown bat, Eptesicus fuscus. The best frequency (BF) and minimum threshold (MT) of each recorded neuron were first determined with a 4 ms pulse delivered from a specific point of the bat's frontal auditory space at which the neuron had maximal spatial sensitivity. Then a 4 ms pulse was delivered repetitively at different rates with an intensity in 10 dB increments above the neuron's MT and its number of impulses and response latency to each combination of repetition rate and intensity were recorded. From the series of isorepetition rate-intensity functions, we identified the neuron's best intensity (BI) which elicited a maximal number of impulses. By using a 4 ms BF and BI pulse delivered at a wide range of repetition rates, we then determined the neuron's best repetition rate (BRR) to which the neuron discharged maximally. The effect of pulse duration on the neuron's responses was subsequently studied by recording its number of impulses and latency to a BF, BI and BRR pulse delivered at a wide range of durations. A neuron's best duration (BD) to which the neuron discharged maximally was also identified. We found that cortical neurons sequentially isolated with an orthogonally penetrated electrode have comparable BFs, MTs and latencies. In addition, high BF neurons tend to have higher MTs and shorter latencies than low BF neurons. Most intensity-rate functions of cortical neurons were nonmonotonic but they can be affected by pulse repetition rate. Under repetitive single pulse stimulation, all cortical neurons show low pass characteristic to pulse repetition rate such that their number of impulses reduced drastically with increasing pulse repetition rate regardless of pulse intensity. The BRRs of most cortical neurons studied are between 1 and 3 pulses/s and their BDs are between 0.5 and 10 ms. Response latencies of cortical neurons generally shortened to a plateau level with increasing pulse intensity. In contrast, they increased with pulse repetition rate and varied in different manner with pulse duration. Nevertheless, a cortical neuron generally responds with a shortest latency to a pulse delivered at its BF, BI, BRR and BD. Thus in auditory signal processing, a neuron's responses to a wide combination of pulse intensity, duration and repetition rate enhance its versatility in signal detection. Its maximal response to a specific combination of signal duration, repetition rate and intensity provides a neural basis for fine analysis of signal features. PMID- 1308733 TI - Phonology and orthography in visual word recognition: evidence from masked non word priming. AB - Three lexical decision experiments in French investigated the effects of briefly presented forward-masked non-word primes on latencies to phonologically and/or orthographically related targets. At 64-msec prime presentation durations, primes that are pseudohomophones of the target produced facilitatory effects compared to orthographic controls, but these orthographically similar non-word primes did not facilitate target recognition compared to unrelated controls. These results were obtained independently of target word frequency and independently of the presence or absence of pseudohomophone targets in the experimental lists. With a 32-msec prime duration, on the other hand, pseudohomophone and orthographic primes had similar effects on target recognition, both producing facilitation relative to unrelated controls. The results are discussed in terms of the time course of phonological and orthographic code activation in the processing of pronounceable strings of letters. PMID- 1308732 TI - Neurofibrillary degeneration and microtubule associated protein tau. AB - Alzheimer disease is characterized by neurofibrillary pathology containing paired helical filaments (PHF). These abnormal filaments consist of a modified form of microtubule associated protein tau. The modification involves phosphorylation. In this mini review, we summarize recent studies regarding the differences between normal tau and PHF-tau, focusing especially on the extent and the site of phosphorylation. We also discuss the mechanisms possible involved in the development of PHF. PMID- 1308734 TI - Do visual images have Gestalt properties? AB - Recent research has demonstrated that percepts and images share processing resources. A natural consequence of this evidence is to ask what kind of properties are shared by the two representational systems, i.e. images and percepts. To what degree, for example, do images share the complex organization of visual percepts? This paper investigates whether percepts and images share Gestalt properties. Four experiments were conducted to study this hypothesis. In all experiments subjects were presented with an auditory message in which approximately 15 locations in a matrix were defined by giving the co-ordinates of the cells. Half of the stimuli presented some "good" form, whereas in the other half the locations of the pieces were scattered. Subjects were systematically less able to recall the locations of the random forms. Therefore, it could be argued that the "good" forms help in image construction, even though the elements were auditorily presented. Effects of varying presentation speed, order, and of requiring a mental rotation before recall support this conclusion. PMID- 1308735 TI - The representation of objects and their attributes in memory: evidence concerning memory for location. AB - The general principle is advanced that different attributes of objects (e.g. shape and colour) are more readily associated when they are attributes of the same object than when they are attributes of different objects. Previous studies provide support for the principle, for they have shown that a shape is more readily associated with its own colour than, for example, with the colour of its background. In the present experiments, the principle was applied to the attributes of shape and location. In four experiments it was shown that a shape was more readily associated with its own location than with the location of another object. Differences in contiguity between the presentation of the shape and the location with which the shape was to be associated were controlled for, as were other factors. The results were interpreted as providing support for the general principle stated above. It was suggested that the general principle could be explained by supposing that memory is propositional in format. PMID- 1308737 TI - [Control of foodstuffs in international turnover. I. Documents of the European economic community]. AB - Council Directive (89/397/EEC) is presented which harmonize official control of foodstuffs. The main principles are given, obligatory for the Member States, concerning control of foodstuffs, food additives and materials intended to come into contact with foodstuffs performed by home authorities. The proposal of supplementary Directive is discussed, dealing with problems of qualification and competence of laboratory personnel, introduction of quality assurance systems in the laboratories and the system of information exchange of foodstuffs within the Common Market. PMID- 1308736 TI - An anxiety-related bias in semantic activation when processing threat/neutral homographs. AB - Three experiments are reported comparing high- and low-trait anxious subjects in terms of their patterns of semantic activation in response to ambiguous primes, with one threat-related and one neutral meaning. Such primes were followed by targets related to either their threat or neutral meaning, or by unrelated targets, in a lexical decision task. Experiments 1 to 3 employed stimulus onset asynchronies (SOAs) of 750 msec, 500 msec, and 1250 msec, respectively. At 500 msec SOA all subjects showed facilitation for both meanings. At 750-msec SOA the only significant priming effect was that for the threat-related meaning in the high-anxiety group, and a similar trend was found at 1250-msec SOA. Consideration of the patterns of priming for targets following ambiguous threat/neutral primes suggest that at the longer SOAs, high-anxiety subjects consciously "lock on" to a threatening interpretation if one has been made available by earlier automatic spreading activation. PMID- 1308738 TI - [Problem with the presence of carcinogenic substances formed spontaneously or during technologic processing in food]. AB - The current opinion on the spontaneously occurring or evoked by certain culinary and technological processes muta-, cancero- and teratogenic compounds are reviewed on the basis of the world literature. It was noted that these substances may form in food products of vegetal origin. Formation of carcinogenic compounds is more intensive in plants attacked by various diseases, insects or parasites. The importance of this problem should be stressed together with the need of improving knowledge in this field. The compounds under discussion are the most serious risk factor in the incidence of neoplasms in humans. PMID- 1308740 TI - [Determination of antibiotic residues in some food products of animal origin]. AB - Food products of animal origin were analysed in years 1986-1990 by Sanitary Epidemiological Stations for the presence of antibiotics residues-chloramphenicol and streptomycin. In raw milk chloramphenicol (trace) was found in 9 out 938 samples, streptomycin (3.66-19.67 ppm) in 28 out 251. In eggs chloramphenicol (trace) was present in 5 out 866 samples. In milk powder chloramphenicol was not detected. PMID- 1308739 TI - [Estimation of table salt content in daily food rations of children, youth and elderly people]. AB - In order to estimate table salt intake in selected population groups, sodium chloride as well as sodium, potassium were determined in daily food rations. Sodium chloride was determined by Mohr's method, while sodium and potassium by flame photometry. Parallel samples of soups, bread and carbohydrates in the second courses were analysed in the same way. Samples for analysis were collected during a period of 10 days in a State Children's Home (SCH) and in Home for the Aged (HA). The table salt content in food rations from the HA was found between 14.7-24.7 g and in rations from the SCH between 7.9-19.6. In both cases the values were significantly higher than those recommended. The average table salt content in soup from the HA was 1.24 g/100 g and that from the SCH -1.65 g/100 g. A high level of salt was observed also in potatoes, groats and macaroni, the average value being 1.5 g/100g. As regards the size of the portions given, it was found, that soups as well as bread supplied 34% of the total salt content in the food rations, and the carbohydrates in the second courses brought about 14%. It was found, that about 96% of the total salt quantity in the investigated rations was derived from addition of salt during food preparation and from the processed products. The studied food rations contained relatively high quantities of potassium, that completely satisfied the demand for this element of the investigated population groups. The Na:K weight ratio was abnormal, as the results of too high sodium content. PMID- 1308741 TI - [Evaluation of degree of freshness and value of fish and fish product t intake based on histamine and trimethylamine analysis]. AB - The results of histamine and trimethylamine determination in three fish species (cod, herring, scomber) of various freshness are presented. In fresh fish the histamine contents were s follow: cod 0.00; scomber 1.00; and herring 0.50 mg/100 g. During storage time at room temperature (+18 degrees C), the value of the freshness indicators increased after 24 and 48 hours of storage. The highest increase was observed in scomber (21.30 and 34.00 mg/100 g), the lowest in cod (2.00 and 4.00 mg/100g). The trimethylamine value increased in different order than the histamine in the fish species. The highest TMA amount was observed in cod flesh--the lowest in scomber. According to these findings the freshness of some ready fish products was determined. The histamine level never exceeded 6 mg/100 g, always being below the "safety level" (= 10 mg/100g). The value of TMA never exceeded the limits considered for fresh fish products--15 mg N per 100 mg sample. PMID- 1308742 TI - [Effect of the fermentation process on levels of nitrates and nitrites in selected vegetables]. AB - The aim of this study was to follow the changes in the levels of nitrates and nitrites throughout the process of fermentation of sauerkraut from white and red cabbage and red beets. The nitrate and nitrite levels were determined in raw and fermentation as well as in red beets and "beet acid" after a week of souring. Nitrate were determined by the brucine method, while nitrates by the Griess colorimetric method. Mean reduction of nitrates in sauerkraut (in relation to raw cabbage) was ca. 55.5% and that of nitrites ca. 76.7%. In the red sour cabbage a decrease in the level of nitrates in relation to the product by ca. 84.1% and in that of nitrites by ca. 67.4% was found. The stabilization of both nitrate levels in both kinds of cabbages followed as after the second month of storage, as confirmed by statistical analysis of the results. In the red beets after the process of fermentation a decrease in the level of nitrates by ca. 91.6% was noted. An undefined portion of the studied compounds passed into the liquid. The "beet acid" contained 595.9 mg/dm1 of nitrates and 3.26 mg/dm3 of nitrites. PMID- 1308743 TI - [Nitrate water pollution of drinking water in the Bydgoszcz district]. AB - The study was undertaken to evaluate the degree of drinking water pollution in the towns and countryside of the Bydgoszcz District, supplied by various installations, on the basis of the results of investigations of sanitary epidemiological stations. Evaluation was done according to the state in 1985 as compared with that of 1981 to establish the eventual dynamics of the changes. The data presented in the tables indicate that the water supplied by the big water lines (public and institutional) does not contain nitrate quantities exceeding the norm (above 10 mg N/dm3). Their presence at a 20 mg N level/dm3 was found only in four (1.5%) lines supplying large state farms. Small installations were much more frequently polluted with nitrates, especially public wells and those of local institutions, a total of 8.8% in towns and as many as 17% in the country, where a tendency to deterioration of this state is also visible in contrast to the towns. Among the plants and institutions supplied by these water sources the situation is most unfavourable in agriculture, schools, educational and food producing and distributing establishments. The nitrate concentration in the analysed water varied in general within the limits of 10-30 mg N/dm3, maximal amounts within 60-200 mg N/dm3, showing an about 50% decrease in the compared time periods. Nitrates occur most frequently and in highest concentrations in water of wells belonging to individual households which supply about 50% of the rural population and about 11% of town dwellers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308744 TI - [Three cases of methemoglobinemia following nitrite intoxication]. AB - Three children of nitrate oral intoxication with symptoms of meta-hemoglobinemia and respiratory insufficiency have been described. All cases have been recovered. PMID- 1308745 TI - [Detection of carcinogenic compounds in the environment with special regard to tests on fruit flies (Drosophila melanogaster)]. AB - The increasing exposure of the human population to mutagen and carcinogenic substances necessitates research and introduction of methods for their detection. The diversity of these dangerous substances in the environment requires, the application of the chemical and biological tests. The latter allow testing of chemical mixtures of unknown composition. The advantages and limitations of short term tests are presented. Among these the advantages of somatic mutation and recombination tests are described in more detail on Drosophila melanogaster. The subcellular structure, enzymes produced and the course of metabolic processes in Drosophila are similar as in man. It is possible, therefore, to detect the numerous mutagens undetectable in tests on bacteria. These test are relatively simple, not expensive and do not require expensive apparatus or preliminary activation of promutagens necessary in tests on bacteria. PMID- 1308746 TI - [Effect of histamine application on diamine oxidase activity in kidneys and histamine level in urine]. AB - Histamine or cadaverine or both amines jointly were given to guinea pigs for 7 weeks. The histamine content was determined in urine and the diamine-oxidase activity in the kidneys. Histamine excretion by the kidneys occurred 4 hours after introduction of the amine into the stomach. In the animals receiving histamine the activity of diamine-oxidase was greatly enhanced. PMID- 1308747 TI - [Determination of formaldehyde using the colorimetric method with acetylacetone. I. Determination of formaldehyde in selected cosmetic products]. AB - Total formaldehyde content was determined by the colorimetric method with acetylacetone in shampoos and foam baths. The commercial products containing formaldehyde were fortified with a solution of this compound of various amounts. Recovery in this method was 91.7-98.7%. The method was found useful in routine determinations of formaldehyde in shampoos and foam baths and can be used by the State Sanitary Inspection. PMID- 1308748 TI - [Occurrence of bacteria of the Yersinia genus in surface water]. AB - The aim of the study was determination of the frequency of occurrence of Yersinia genus bacteria in surface waters polluted to various degrees with bacteria of the coliform and of fecal coli. For detection of Yersinia rods the previously elaborated medium Endo MLCe and the membrane filter method were applied. Samples of 42 surface waters were examined, including 26 from rivers and 16 from lakes, ponds and clay-pits. On the basis of sanitary bacteriological analysis 16 surface waters were classified to class I purity, 10 to class II, the remaining ones to class III or beyond classification. Yersinia rods were detected in 15 water bodies that is 35.7% of the examined waters. A total of 27 Yersinia strains were identified with dominance of Y. intermedia (14 strains) and Y. enterocolitica (10 strains). Three strains represented by the species Yersinia frederiksenii. Most of the Y. enterocolitica strains belonged to biotype 1, the particular strains being represented by various serotypes. Hence their different origin may be concluded. The pathogenic serotypes 0:3 and 0:9 of Yersinia enterocolitica were not detected. PMID- 1308749 TI - [Evaluation of school milieu as an aspect of conditions for realizing health promotion. I]. AB - Data collected in 1990 by workers of children and youth hygiene section of the Sanitary Epidemiological Station were analysed in randomly chosen elementary schools of 41 districts. In elaboration of the data negative observations were singled out. There were differences between schools of various milieus. A regularity was noted: the smaller the locality, the more there are shortcomings and neglect. Teaching in shifts was general: in at least two relays in 90% of town schools and 50% of village ones. Many shortcomings were noted in the functioning of WC and washing equipment (lighting, heating, ventilation), besides 10% of village schools had no washing facilities. About 60% of town schools had showers bath but they were hardly utilised; 1/4 of village schools had shower baths but did not profit of them. In the sanitary-hygienic state frequent negligence was visible. For instance in 1/4 of what used to be communal schools the WC were dirty, without toilet paper, and less than half of them had neither soap nor towels. Lousiness indexes were as follows: 1.6% (if 140,000 individuals examined) in town schools and 2.5% (of 65,000 examined). Lousiness was recorded in more than 60% of schools. The staff of the schools health service may be described by the following data: in 85% of village schools the physician appeared at most several times in the course of the year, in town schools he was present at most several times in a month; in 50% of village schools a nurse was seen less frequently than one a week, and in 85% of town schools three or more times weekly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308750 TI - A proposal for the Polish norm of PKA and KK content in plasma-derived preparations. PMID- 1308751 TI - Erythro-toxicity of dichlorvos and possibility of its modification in vitro. AB - The purpose of this study was to investigate the in vitro effects of dichlorvos (organophosphorous pesticide) on the biological value of erythrocytes; an in vitro test of erythrocyte protection against DDVP effects was also included. A significant decrease of glutathione level with concomitant increase of methemoglobin and denatured hemoglobin levels, as well as a rise of Heinz body number were observed after 24 h following the treatment with dichlorvos (100 microM). Preincubation of erythrocytes with glutathione prevented the toxic effects of the pesticide with the maintenance of both glutathione and methemoglobin at a control level. PMID- 1308752 TI - [The influence of DDT analogues (nuarimol and fenarimol) on the frequency of occurrence of micronuclei in erythrocytes of bone marrow and spleen in mice]. AB - The clastogenic potential of the two DDT analogues: fenarimol and nuarimol was investigated, and the usefulness of the mouse spleen cells for this purpose was evaluated. Nuarimol and fenarimol were administered per o to 8-10 weeks old male mice (Swiss) according to the following protocol: nuarimol 100 and 200 mg/kg b.w. and fenarimol 50 and 100 mg/kg b.w. twice during 24 hours. Mitomycin C (2 and 4 mg/kg b.w.) and cyclophosphamide (25 and 75 mg/kg b.w.) were administered to the positive control mice. After 30, 48, 72 hours following the first administration the animals were killed and the number of micronuclei were calculated in spleen and bone marrow polychromatic and normochromatic erythrocytes. The results show that the spleen could be regarded as an appropriate tissue for the evaluation of micronuclei induction. Fenarimol and nuarimol did not cause micronuclei induction in the bone marrow and spleen erythrocytes. PMID- 1308753 TI - [Studies of certain trace elements in selected internal organs and meat of bulls]. AB - The aim of the study was to determined lead, cadmium, copper, zinc, and iron contents in certain internal organs and meat of young bulls. The material comprised kidney, liver and muscle tissues of 60 bulls from an agricultural region (control group). Contents of lead, cadmium, iron, copper and zinc were determined by atomic absorption spectrometry. It was found that the levels of lead and cadmium in kidney and liver of the bulls from Krakow voivodship, as compared with the agricultural region, were several times higher. PMID- 1308754 TI - [Evaluation of mutagenicity of urine extracts from rats fed a diet containing carbendazim and sodium nitrite]. PMID- 1308755 TI - The Canadian four-centre study of anaesthetic outcomes: I. Description of methods and populations. AB - The objectives of this study were first to develop and institute a methodology for the study of anaesthetic outcome for parallel use in four teaching hospitals in Canada and second, to compare rates of morbidity and mortality associated with anaesthesia between the four centres. The basic design of the study was occurrence screening with anaesthetists entering data on patient demographics, anaesthetic and surgical factors. Research nurses reviewed anaesthetic records and hospital charts and interviewed patients postoperatively. Data on 37,665 anaesthetics were collected during 1988-89 in the four teaching centres. There were major differences found across the hospitals, particularly with regard to volume, patient case-mix, anaesthetic drugs and monitoring used. The use of parallel training, repeated consultations and use of rounds and inservices contributed to the reliability and validity of the data collection. We conclude that outcome surveillance can be instituted in different hospital Departments of Anaesthesia with sufficient confidence to form the basis of comparison of anaesthetic outcome. PMID- 1308756 TI - Age as a factor in breast cancer knowledge, attitudes and screening behaviour. AB - OBJECTIVE: To determine whether there are age-related differences in knowledge, attitudes and behaviour with respect to breast cancer and whether the differences reflect the age-specific Canadian recommendations on breast cancer screening. DESIGN: Telephone survey. SETTING: Two cities and five towns and their surrounding areas in Alberta. PARTICIPANTS: The age-specific, randomly selected sample comprised 1284 women aged 40 to 75 years who did not have breast cancer. Of the 1741 eligible women who were contacted, 1350 (78%) agreed to participate; 66 were excluded because of age ineligibility or a history of breast cancer. MAIN OUTCOME MEASURE: Frequency of knowledge, attitudes and behaviour with respect to breast cancer, by age group. RESULTS: Knowledge of breast cancer risk factors was generally low and decreased with age. Few women were aware of the Canadian recommendations on breast self-examination, physical examination of the breasts by a health care practitioner and mammographic screening. Older women believed they were less susceptible to breast cancer than younger women and were less likely to have positive attitudes toward screening. Self-examination was performed 9 to 15 times per year by 424 women (33%), and 810 (63%) had been examined by a health care professional in the past year. Although 664 (52%) had undergone mammography, the proportion decreased with age after age 59. The main barriers to mammography were lack of physician referral and the woman's belief that the procedure is unnecessary if she is healthy. CONCLUSIONS: Education is needed to increase breast cancer knowledge, promote the Canadian recommendations for early detection of breast cancer and decrease negative beliefs about the disease. Changes in the behaviour of women and physicians are needed to increase the use of breast self-examination, clinical breast examination by a health care professional and mammographic screening. Reaching women in the upper range (60 to 69 years) of the target group for mammographic screening should be a focus in promoting early detection of breast cancer. PMID- 1308757 TI - Direct thrombosis of aneurysms with cellulose acetate polymer. Part I: Results of thrombosis in experimental aneurysms. AB - The authors have developed a liquid material for thrombosing aneurysms. This material is a mixture of cellulose acetate polymer and bismuth trioxide dissolved in dimethyl sulfoxide. On contact with blood, the dimethyl sulfoxide diffuses and cellulose acetate polymer forms, which balloons when slowly injected into the blood. The polymer solidifies from surface to core in 5 minutes. Cellulose acetate polymer was injected directly into experimental aneurysms created in 10 dogs; it rapidly hardened in the shape of the aneurysms, completely obliterating them but preserving the parent vessels in all cases. No distal migration of the polymer was seen. The good results of this experimental trial led to a clinical study using a cellulose acetate polymer, as described in Part II. PMID- 1308758 TI - Cancer and clotting--Trousseau's warning. PMID- 1308759 TI - Inappropriate medication prescribing in skilled-nursing facilities. AB - OBJECTIVE: To quantify the appropriateness of medication prescriptions in nursing home residents. DESIGN: Prospective, cohort study. SETTING: Twelve nursing homes in the greater Los Angeles area. PARTICIPANTS: A total of 1106 nursing home residents. MAIN OUTCOME MEASURES: The appropriateness of medication prescriptions was evaluated using explicit criteria developed through consensus by 13 experts from the United States and Canada. These experts identified 19 drugs that should generally be avoided and 11 doses, frequencies, or durations of use of specific drugs that generally should not be exceeded. RESULTS: Based on the consensus criteria, 40% of residents received at least one inappropriate medication order, and 10% received two or more inappropriate medication orders concurrently; 7% of all prescriptions were inappropriate. Physicians prescribed a greater number of inappropriate medications for female residents. Regression analysis, corrected for clustering effects within facilities, showed that a greater number of inappropriate medication prescriptions were ordered in larger nursing homes. Inappropriate prescriptions were not related to the proportion of Medicaid (Medi Cal) residents or the number of physicians practicing in the homes. CONCLUSIONS: Inappropriate medication prescribing in nursing homes is common. Female residents and residents of large nursing homes are at the greatest risk for receiving an inappropriate prescription. PMID- 1308760 TI - The influence of standard of care and severity of injury on the resolution of medical malpractice claims. AB - OBJECTIVE: To explore how frequently physicians lose medical malpractice cases despite providing standard care and to assess whether severity of patient injury influences the frequency of plaintiff payment. DESIGN: Retrospective cohort study. SETTING: Physicians from the state of New Jersey insured by one insurance company from 1977 to 1992. PARTICIPANTS: A total of 12,829 physicians involved in 8231 closed malpractice cases. MEASUREMENTS: Physician care and claim severity were prospectively determined by the insurance company using a standard process. RESULTS: Physician care was considered defensible in 62% of the cases and indefensible in 25% of the cases, in almost half of which the physician admitted error. In the remaining 13% of cases, it was unclear whether physician care was defensible. The plaintiff received a payment in 43% of all cases. Payment was made 21% of the time if physician care was considered defensible, 91% if considered indefensible, and 59% if considered unclear. The severity of the injury was classified as low, medium, or high in 28%, 47%, and 25% of the cases, respectively. Severity of injury had a small but significant association (P < 0.001) with the frequency of plaintiff payment (low severity, 39%; medium severity, 43%; and high severity, 47%). The severity of injury was not associated with the payment rate in cases resolved by a jury (low severity, 23%; medium severity, 25%; and high severity, 23%). CONCLUSIONS: In malpractice cases, physicians provide care that is usually defensible. The defensibility of the case and not the severity of patient injury predominantly influences whether any payment is made. Even in cases that require a jury verdict, the severity of patient injury has little effect on whether any payment is made. Our findings suggest that unjustified payments are probably uncommon. PMID- 1308761 TI - Homeopathy treats people, not the soles of their feet. PMID- 1308762 TI - Effective dose from radiopharmaceuticals. AB - The effective dose, as defined by the International Commission on Radiological Protection (ICRP 1991), provides a possibility of expressing the radiation risk to patients undergoing different radiodiagnostic procedures by means of a single figure. This has been obtained by introducing organ or tissue weighting factors reflecting the radiation sensitivity of the organs. Such weighting factors were first published by the ICRP in publication 26 (1977), and have now been revised in publication 60 (1991). The effective dose for almost all radiopharmaceuticals in clinical use has been recalculated using the new weighting factors from ICRP 60 (1991) and compared with results from former calculations. A slight decrease in the numerical value for the effective dose has been observed, on average 11%. However, this does not correspond to a decrease in the estimated risk from the irradiation, since this has been re-evaluated and found to be higher than earlier believed (NAS 1990; ICRP 1991). PMID- 1308764 TI - Romuald Weglowski. PMID- 1308763 TI - Afferent and efferent connections of the paramedian reticular nucleus in the brain stem of cats. AB - Anatomical connections of the paramedian reticular nucleus (PRN) of the caudal medulla were investigated using a bi-directional tracer, horseradish peroxidase (HRP). The followings were observed when the tracer was microinjected to PRN: A. Both labelled neurons and terminals were found in the areas of the mesencephalic cardioinhibitory mechanism (CIM), the gigantocellular reticular nucleus (GRN), the ambiguus nucleus (AN) and the contralateral PRN. B. Only labelled terminals were demonstrated in the area of the nucleus of solitary tract (NTS) and the intermedial lateral cell column (IML) of the spinal cord. C. Only retrogradely labelled neurons were observed in the areas of the dorsal and dorsomedial medulla (DM) and ventrolateral medulla (VLM). A few labelled neurons were observed in the periaqueductal gray, the cuneiform nucleus and superior colliculus of the mesencephalon as well as the alamina spinal trigeminal nucleus. When HRP was applied to the CIM, GRN or AN structures, respectively, both labelled cells and terminals were found in the PRN area. HRP injection in the VLM showed only labelled terminals in the PRN. However, injection of HRP to DM showed neither labelling neurons nor terminals in PRN. Results suggest that PRN projects to the pressor area of DM/NTS and IML through which PRN could exert its inhibitory functions on the sympathetic pressor actions. In addition, PRN may suppress the vagal bradycardiac action through its reciprocal connections with CIM, GRN and AN. No lateralization in the PRN pathway was evident. PMID- 1308765 TI - Epidemiology of dengue/dengue hemorrhagic fever in Malaysia--a retrospective epidemiological study 1973-1987. Part I: Dengue hemorrhagic fever (DHF). AB - Dengue hemorrhagic fever (DHF), though endemic in the sixties, emerged as a major public health problem in Malaysia from 1973 onwards. The incidence rate of DHF which was 10.1 per 100,000 in 1973 has fallen down to 1.9 per 100,000 in 1987 with a mean case fatality rate of 6.4 per 100 persons. The Chinese appear to be more prone to DHF with the highest mean morbidity rate of 5.5 per 100,000 and case fatality rate of 6.1%. The incidence of DHF is higher in the males with a higher case fatality rate in females. Male Chinese appear to be mainly affected. The overall age-specific incidence rate is highest in two age groups, viz. 5-9 years and 10-19 years of age with a mean morbidity rate of 4.9 cases per 100,000. The mean age-specific case fatality rate was highest in the 0-4 years age group. Dengue hemorrhagic fever is predominantly an urban disease in Malaysia with a mean incidence rate of 5.3 cases per 100,000 as opposed to 1.2 cases per 100,000 being reported from rural areas. The mean overall incidence of deaths in the urban area is 0.5 compared to 0.1 per 100,000 for rural areas. There is a marked seasonal correlation between DHF cases and rainfall, with a peak in August. While all four serotypes of dengue viruses are found in Malaysia, Den 2 appears to be isolated with greater frequency during all the epidemics. PMID- 1308766 TI - 1993 Professor Kazue K. McLaren Leadership Achievement Award. PMID- 1308767 TI - The managerial process as a key to successful breastfeeding for promoting infant health in Thailand. AB - A strengthening of the managerial process within the health care delivery system can facilitate and encourage successful breastfeeding. This process includes problem-based planning, multidisciplinary team approach, leadership development and generation training. The process has proved to be very successful in promoting breastfeeding and improved infant health. It can be applicable to other urban settings throughout Thailand and perhaps to other developing countries. PMID- 1308768 TI - The interaction of lead exposure and pregnancy. AB - The toxic effects of low-level lead exposure have been the subject of a good deal of research and media attention in recent times. In most countries, the acceptable occupational exposure limit for lead is being progressively decreased as the adverse health effects of lead are being identified at levels approaching those found in non-occupational environments. Due to the sensitive nature of the fetus to hazardous substances, the exposure to lead of the unborn child via maternal sources is of critical concern. Preterm delivery, congenital abnormalities and decreases in growth stature have all been associated with prenatal lead exposure at "acceptable" levels. There is an accumulation of evidence which indicates that maternal exposures prior to conception can play an important role in determining blood lead levels during pregnancy. In light of these observations the practice of removing the pregnant woman from lead sources may be of questionable value with regards to providing sufficient protection for the fetus. This article reviews the relevant literature pertaining to the mobilization of lead from bone during pregnancy and the toxicity of low-level lead exposure to the fetus, and briefly discusses some factors which may affect this toxicity. PMID- 1308769 TI - APACPH Public Health Recognition Award. PMID- 1308770 TI - Environmental biotechnology: biotechnology solutions for a global environmental problem, hazardous chemical wastes. AB - Biotechnology has a growing place in the remediation of hazardous waste sites throughout the world, and especially in Asia where population density is high and land and fresh water are scarce. In-situ bioremediation has been demonstrated already to be highly effective for petroleum hydrocarbons (alkanes, aromatics, polychlorophenols) and organophosphate pesticides in soils and for gasoline by products (benzene, toluene, xylene) and chlorinated solvents (trichloroethylene) in groundwater. Heavy metals and PCBs are not suitable for bioremediation. Environmental biotechnology includes solid-phase and slurry-phase bioremediation for contaminated soils and site-specific bioreactors for contaminated groundwater. Specific examples are presented. From a policy point of view, accumulated wastes must be detoxified, preferably at sites where they already exist. We cannot continue to rely on their removal and disposal "elsewhere". For current waste streams, we must minimize the volumes and toxicity. Environmental biotechnology will play a key role. PMID- 1308771 TI - Pacific health: an analysis for training new leaders. AB - History, economics, culture, and politics have created health systems that can no longer meet the health challenges in the Pacific. An analysis of the health situations in the region revealed health trends, health service deficiencies and the various issues that need to be addressed. The morbidity and mortality experience in the Pacific has been approaching that of the developed countries. The contributing factors to diseases and death have been changing but other health issues, such as matters pertaining to environmental sanitation, management, health information, food and nutrition, ethnic pluralism, colonialism, and technological arrogance, may exacerbate these experiences. To appropriately meet these constraints, the health services need reorientation. However, these need new types of health leadership. Doctors, being the most socially acceptable and politically powerful, should be trained for this new leadership role. This training must be guided by the biopsychosocial model to produce community health physicians. This is being undertaken at the Pacific Basin Medical officer Training Program, Pohnpei. It is characterized by an integrated, community-oriented, student-centered, career-ladder and competency based approach. The graduates will then provide the leadership and catalyst for the needed health service reorientation. PMID- 1308772 TI - Attempted suicide in Kuala Lumpur. AB - A total of 306 patients were admitted to the University Hospital in Kuala Lumpur in 1989 after attempting suicide. Fourteen of them succumbed to injuries. Psychosocial data of 296 patients out of the 306 survivors are reported. Suicidal behaviour is more common in the young and especially amongst the females. Nearly 45.0% of them are from social class IV and V. Persons of Indian ethnic origin are overrepresented, while in Malays suicidal behavior seemed to be less common. Self poisoning was reported to be the commonest method in attempting suicide. Diagnosis of adjustment disorder was made in 58.5% of the patients. Two-thirds of the patients had an intention score of less than 10 on the Pierce's Scale. PMID- 1308773 TI - Effectiveness of a worksite nutrition education activity in a factory in China. AB - To evaluate the effectiveness of a worksite nutrition education activity in China, a two-group pretest-posttest nutrition education lesson was designed and carried out in two divisions (N = 240 in each division) of a steel tube factory in Chengdu, Sichuan. Special features of the program were nutrition education materials developed from both (a) the results of a pretest survey of the employees, and (b) focus group discussions conducted with factory hospital and workteam staff; a colloquial style; a slogan; and an illustrated handout depicting the new Chinese Dietary Guidelines and a proposed Food Guide. Analysis of variance, chi-square, and t-tests showed both significant increases (p < 0.05) in nutrition knowledge and attitude scores and significant improvements in dietary practices in the group receiving the education. It is concluded that the method is a useful and practical model for designing and developing worksite nutrition education in China. PMID- 1308774 TI - Fiber optic surface fluorometry-reflectometry technique in the renal physiology of rats. AB - Most current knowledge on events in the mitochondria leading to acute renal failure originates from studies in which indirect methods were used. The disadvantage of these methods is that they cannot measure the turnover rate of various metabolites, and only one result per animal can be obtained. Chance et al. /9/ developed a method using optical techniques for continuously monitoring the fluorescence of intramitochondrial NADH, which has been applied mainly to the brain. This optical method has not yet been examined quantitatively in the kidney and no attempt has been made to adapt this method for routine measurement in kidney tissue. The purpose of this study was to adapt the surface fluorometry method for monitoring renal NADH redox state in situ, and to determine whether the hemodynamic artifacts involved in fluorometric studies of the renal surface in situ could be eliminated by using a correction factor. Another purpose was to understand the relationship between the changes in reflectance and blood volume in the rat kidney. This was achieved by measuring the reflectance after: a) blood exchange by FC-43 emulsion; b) intrarenal saline flush; c) occlusion of the renal vein, renal artery and reopening of the renal vein; d) calculation of the correlation between changes in kidney weight after renal artery occlusion, and the reflectance. Our results suggest that in the rat kidney, as opposed to the brain, a correction factor of 1:1 is not always applicable. This factor may vary between animals, and it is therefore necessary to adjust it electronically for each rat kidney. This observation contradicts the view suggesting a constant correction factor of 1:1 in the kidney. The results reported herein indicate that changes in the reflectance in the ischemic rat kidney are due to changes in blood volume. In conclusion, it seems that optical techniques for monitoring fluorescence are suitable for localized, continuous and non-invasive recording of tissue mitochondrial NADH redox states under various conditions in the rat kidney. PMID- 1308775 TI - Clinical studies on juvenile, rapidly progressive and adult periodontitis before and after periodontal therapy (I). AB - The sample in the present study comprised 36 patients who were referred for treatment of periodontal disease. Twenty-four of them were early onset periodontitis (EOP) patients and 12 were adult periodontitis (AP) patients. Based upon the age, number of involved teeth and the location of diseased sites, the EOP patients were divided into two groups as juvenile periodontitis (JP) and rapidly progressive periodontitis (RPP). All the patients were individually examined both clinically and radiographically. At a baseline examination and 3 months after active therapy, the patients were evaluated for plaque, gingivitis, probing depths and probing attachment levels. Following instruction in proper oral hygiene measures, all of the patients were subjected to periodontal treatment. Treatment comprised scaling and root-planing, occlusal adjustment, tetracycline administration and periodontal surgery with osteoplasty. Results showed that age limits between JP and RPP cannot be drawn with certainty. The mean age for the JP group was 21.83 years and was 30.58 years for the RPP group. The number of involved teeth was found to increase with age. The first molars were the most frequently affected teeth followed by the incisors. Three months after active treatment, the response of periodontal tissues to therapy both in EOP and AP groups was almost identical. PMID- 1308776 TI - Diagnostic studies on juvenile, rapidly progressive and adult periodontitis before and after periodontal therapy (II). AB - The use of antibody levels may identify subjects developing destructive periodontitis or provide markers of disease type. Clinical parameters can be used to group cases but they are incapable of detecting differences in host susceptibility and host immune response. The validity of radial immunodiffusion (RID) as a laboratory screening method in diagnosis based on antibody quantitation has been evaluated in 36 patients before and after periodontal therapy. It was concluded that the serum IgA, IgG, IgM and parotid IgA concentration profiles, measured with RID have little value in determining the subgroups of early onset periodontitis patients but they can be used to differentiate these groups from slowly progressing adult periodontitis patients. PMID- 1308777 TI - The fit of all-ceramic crowns cemented with different luting agents. AB - In this article the fit of all-ceramic crowns, cemented with different luting agents (zinc phosphate and resin cements), was investigated using a scanning electron microscope. The marginal opening of all-ceramic crowns cemented with zinc phosphate cement was 111.9 +/- 40.6 microns which was significantly greater than the 46.7 +/- 12.9 microns marginal opening of Cerestore crowns cemented with resin cement. Total film thicknesses of the cements were not uniform and there were certain discrepancies from margins to walls and to tip due to the die spacer. PMID- 1308778 TI - The incidence of mandibular premolars with more than one root canal in a Turkish population. AB - One hundred and eighty seven mandibular premolars taken from a Turkish population were examined in this study. The teeth were soaked in India ink and then decalcified, cleared and used in an in vitro study to determine the number of root canals and their types, the ramifications of root canals, the location of apical foraminae and the frequency of apical deltas. It was found that the incidence of more than one canal in mandibular premolars was 27.76%; that of finding two or three separate canals in the same root was 9.62% and that of having more than one canal at the apex was 23.49%. PMID- 1308779 TI - The effect of a sealant on the microleakage of composite resin restorations: an in vivo study. AB - The aim of this study was to evaluate the effect of sealant application in reducing microleakage of the composite resin restorations under in vivo conditions. Occlusal composite resin restorations were made in 24 caries-free primary molars which were about to exfoliate, in children aged between 10 and 13 years. Of these restorations, 12 were sealed with a fissure sealant whereas the others were kept unsealed as controls. After 1 month, the teeth were extracted and immersed in a 2% methylene blue dye solution. The dye penetration alongside the restorations was evaluated using a stereo-microscope. The findings indicated that sealant application significantly (p < 0.05) reduced the microleakage of composite restorations but did not eliminate it completely. PMID- 1308780 TI - Streptococcus mutans in plaque from margins of conventional and high copper amalgam restorations. AB - Levels of Streptococcus mutans in plaque samples from margins of conventional and high copper amalgam restorations were compared in fourteen patients, each having one conventional amalgam filling in each quadrant and one high copper amalgam filling on the contra-lateral side were examined. The percentage of S. mutans of total CFU count in plaque was higher on conventional amalgam than on high copper amalgam. The difference was statistically significant (p < 0.01). PMID- 1308781 TI - The prevalence of Candida albicans in complete denture and removable partial denture wearers: a comparative study. AB - In this study, 60 complete denture wearers, 53 removable partial denture wearers and 50 dentate subjects were examined to determine the Candidal carrier state. The influence of local factors such as denture type, smoking habits and sex on Candidal carrier rate were investigated. Wearing complete or removable partial denture was determined as an important factor increasing Candidal carrier rate. Cigarette smoking is another factor which increases Candidal growth in complete denture and removable partial denture wearers. In contrast to denture wearers Candidal carrier rate was considerably less on dentate smokers. Candidal colonization rate was found to be higher on the dorsum of the tongue. This suggests that the tongue is the primary oral reservoir of Candida albicans in the mouth. PMID- 1308782 TI - A study of chromium, nickel and cobalt hypersensitivity. AB - Hypersensitivity reactions to chromium, nickel and cobalt were investigated in the preclinical, fourth year and fifth year students of the Dentistry Faculty of Marmara University, Turkiye. A Standard patch test was performed. Four patches were applied to the shoulder blades of the students. Three of them contained small amounts of 0.5% potassium chromate, 5% nickel sulphate and 1% cobalt chloride respectively. The fourth (control) patch was of petroleum jelly. Questionnaires were used to determine sex and history of any previous allergy to jewelry. After 48 hours, the patches were removed and results assessed. For each base metal, no statistically significant difference was found in the incidence of hypersensitivity reaction between the groups. Nor was there a significant difference in response found between metals, for all of the students tested. Although women were found to have a higher rate of nickel hypersensitivity than men, no such sex difference was found chromium and cobalt. No significant relationship was found between a history of allergy to jewelry and chromium hypersensitivity, however there was a significant difference for nickel and cobalt hypersensitivity. In confirmation of our tests, significant relationships were found between previous allergy histories and the respective patch test results. PMID- 1308783 TI - Cephalometric evaluation of the therapeutic effects of the Herbst appliance in the treatment of Class II. Div I. malocclusion. AB - The purpose of this investigation was to assess the therapeutic effects of the Herbst appliance cephalometrically. Twenty patients were chosen from our clinical intake. Care was taken to select patients who had Class II Div I malocclusion and horizontal growth pattern. Skeletal age was the main selection criterion. Patients in the peak growth period were chosen. A Herbst appliance was used on the first ten patients. The other ten patients served as controls. Standardized profile roentgenograms were taken initially and at the end of a six month observation period. The following results were obtained: 1. Normal occlusal conditions occurred. 2. The mandible was positioned anteriorly and lengthened due to the Herbst therapy. 3. The most significant effect on the maxilla was the decrease in the 1- SN angle and in overjet reduction. PMID- 1308785 TI - Effectiveness of three cavity varnishes in reducing marginal microleakage of amalgam restorations: an in vitro study. AB - Dentin Adhesit, Cavi-Line and Kavite Lak cavity varnishes were applied to the walls of prepared Class V cavities in fifty-two caries free extracted molar teeth before placing amalgam fillings. Tests with Methylene Blue dye after thermocycling showed that all cavity varnishes showed significantly lesser marginal leakage when compared with the control group without any cavity varnish. PMID- 1308784 TI - Antibacterial effects of ofloxacin, clindamycin and sultamicillin on surgical removal of impacted third molars. AB - This study examined the bacteraemia following surgical removal of impacted mandibular third molars and evaluated the antibacterial effects of Ofloxacin, Clindamycin, Sultamicillin, used as prophylactic medications. The study involved a hundred healthy patients whose mandibular third molars were impacted horizontally. These patients were divided into four groups each including 25 individuals. One of the four groups was the control group. The other groups were those to which Ofloxacin, Clindamycin, and Sultamicillin were administered one hour before the operation and in the following 4 days postoperatively. Blood samples were taken before and immediately after the operation, and then, 1 and 24 hours postoperatively. Following the incubation of the samples under aerobic and anaerobic conditions, the samples were examined microbiologically. Preoperative samples were found to be negative. In the immediate postoperative samples, bacteraemia was found in 44% of the control group, 40% of Ofloxacin and Clindamycin groups and 36% of the Sultamicillin group. In the samples taken 1 hour after the operation, bacteraemia was found in 28% of the control group, 20% of the Ofloxacin group and 24% of the Clindamycin and Sultamicillin groups. In the control group, only 2 cases showed positive culture in the blood samples taken 24 hours after the operation. In conclusion, the antibiotics, Ofloxacin, Clindamycin, Sultamicillin have a significant effect in decreasing the risk of postoperative infection and bacteraemia. PMID- 1308786 TI - Evaluation of the variation in chemical composition and surface topography of different brands of gutta percha cones. AB - There have been many studies on the gutta percha cones used in endodontic therapy. Variations exist between different brands of cone. Since an appropriate cone plays a very important role in the prognosis of therapy, this study examined the surface topography and chemical composition of eight different brands of cone by, a scanning electron microscopy (SEM) and atomic absorption spectrometry. There were some differences between all brands of gutta percha cones. PMID- 1308787 TI - Biguanide related lactic acidosis: incidence and risk factors. AB - The objective of this study was to evaluate in an open population the incidence and risk factors of biguanide related lactic acidosis. All patients currently treated in the Department of Diabetes and Lipid Metabolism of the Instituto Nacional de la Nutricion and their records were reviewed for the present use or history of administration of biguanides. The study was complemented with a revision of all admissions of diabetic patients to the emergency room during 1987 1990. In the outpatient study, 235 cases were included. No case of lactic acidosis was found. A high percentage of the biguanide treated patients had one or more lactic acidosis related risk factors. In the emergency study, 609 admissions of 273 patients were included. In 17 patients a metabolic non-ketotic acidosis was diagnosed. The frequency of non-ketotic acidosis for the different treatments was: 29.4 cases x 1000 emergency admissions for sulphonylurea treated group, 32 for sulphonylurea plus phenformin treated and 47.94 for type II insulin treated patients. All cases had severe precipitant diseases that can cause lactic acidosis with or without associated biguanide administration. No metformin related cases were found. The conclusions of this study are that biguanides in general and metformin in particular are not associated with a high risk of lactic acidosis. Severe systemic dysfunction associated with intercurrent diseases, frequently observed in diabetic patients, is the main determinant for the appearance of lactic acidosis. PMID- 1308789 TI - Oral tolerance impairment in mice with staphylococci-induced wasting syndrome. AB - The effects of staphylococci-induced experimental wasting disease on the immune response of 1 month old CD1 mice were investigated. Animals were separated into different subgroups in order to study their cellular immune competence. Malnutrition of wasted mice was associated with anorexia, diarrhea and weakness. Footpad-injected splenic cells produced normal graft vs. host (GvH) reactions in the popliteal lymph nodes of F1 hybrids. In other experiments, the SRBC intragastric feeding of wasted mice did not cause a tolerant anti-erythrocyte humoral immune response. Three weeks after the staphylococci injections, convalescent erythrocyte-fed wasted mice exhibited an anti-SRBC PFC production similar to that observed in non-tolerant immunized control healthy mice. In return, healthy SRBC-fed control mice showed the specific attenuation of antibody response characteristics of oral tolerance. Differences were found between the immune competence of the undernourished staphylococci-treated wasted mice and those shown by other authors in protein-depleted mice. PMID- 1308788 TI - Effects of G-6-PD deficiency, experimentally induced or genetically transmitted, on the sorbitol pathway activity. In vitro and in vivo studies. AB - Aldose reductase catalyzes the NADPH-linked reduction of hexoses to their respective sugar-alcohols, which are involved in the pathogenesis of "sugar cataracts". In the lenses, the reaction catalyzed by G-6-PD is the source of NADPH supply blocking sugar-alcohol formation and consequently prevents or delays the onset of "sugar-cataracts". We have investigated the effect of G-6-PD deficiency, either experimentally induced or genetically transmitted, on the sorbitol accumulation in whole cells incubated in high glucose media and on the "sugar-cataracts" formation in a galactosemic rat model. We also screened 31 Negro male adults with diabetes mellitus for red cell G-6-PD deficiency. G-6-PD deficiency produced a significant inhibition on sorbitol accumulation in rat lenses and human red cells incubated in 50 mM glucose. In the galactosemic rat model G-6-PD deficiency experimentally induced with acetaminophen delayed the development of cataracts. Finally, two diabetic individuals were G-6-PD deficient and did not show cataracts whereas cataracts were identified in six other diabetic patients. PMID- 1308790 TI - Sperm motility improvement: comparison of two methodologies of reproductive techniques. AB - The objective of this study was to compare two methods for the extraction of high motility sperm; washed semen and swim-up techniques, on 172 ejaculates from 53 patients with suspected infertility. High quality motile sperm had been essential for the success of the assisted reproductive procedures, in which these patients were enrolled. Semen analyses were performed according to the criteria recommended by the WHO. In both methods Ham's F-10 medium plus 7.5% human cord serum were used. The incubations were carried out at 37 degrees C +/- 1. The percentage of motile spermatozoa with forward progression was measured in the fresh sample and after incubation with both methods. The results were analyzed by the two-way analysis of variance. Motility rates were significantly higher in swim-up than fresh samples (mean 41.158%, SD 20.1 vs. 27.572%, SD 16.6; p < 0.0001) and washed semen compared with fresh sample (mean 36.966%, SD 16.3 vs. 27.572% SD 16.6; p < 0.0001). PMID- 1308791 TI - Densitometric validation of nine anthropometric prediction equations of body composition in young native men of Mexico City. AB - Body density by hydrostatic method and anthropometric variables were measured in 29 young males, natives of Mexico City, in order to test the validity of nine currently used equations for predicting body composition. Tested equations were those reported for body density by Sloan, Wilmore, Jackson and Pollock, Durnin and Womersley, Lohman, and Pollock et al.; for lean body weight by Wilmore, and Hume-Rathbun; and for fat percentage by Yuhasz. Mean values for body density, fat percentage and lean body weight obtained by hydrostatic weighing were 1.0560 +/- 0.0149 kg/l, 18.9 +/- 6.7%, and 52.6 +/- 5.3 kg, respectively, while the means for predicted body density using the six regression equations varied from 1.0538 to 1.0654 kg/l, with a range of correlation from 0.846 to 0.900, and total errors from 0.0077 to 0.0124 kg/l. Mean lean body weight predicted by Wilmore was 55.7 +/- 5.9 kg, with an R of 0.902 and a total error of 4.0 kg, while values given in the same order by Hume-Rathbun were 52.8 +/- 4.8 kg, R of 0.892 and total error of 2.3 kg. Mean fat percentage predicted by Yuhasz was 17.8 +/- 5.6%, R of 0.869 and total error of 3.5%. Although by analysis of variance there were no significant differences among the means of the models, statistical analysis of individual differences between predicted and measured values were significant in six of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308792 TI - Effect of a PGE-1 analogue on the survival of cardiac transplant rats. AB - Prostaglandins can be considered as soluble factors of cell-mediated immunity. Studies with animal models have shown that prostaglandins of the series E-1 (PGE 1) can modulate the lymphocyte response to alloantigens. The goal of this work was to evaluate the immunosuppressive effect of a PGE-1 analogue (Enisoprost) on cardiac allograft survival in rats. PGE-1 was given to groups of six rats with heterotopic cardiac transplant. Group 1 was the untreated control group. Group 2a received PGE-1 from 0 to 4 days after transplant and group 2b received PGE-1 from 7 days before transplant to 4 days after transplant. Group 3 was treated with donor-specific blood transfusions (DST) 7 days before transplant. Groups 4a, 4b, and 4c were treated with DST and PGE-1 (0 to 4 days, -7 to 0 days, and -7 to 4 days relative to transplant, respectively). Group 5 was treated with cyclosporine (CsA), groups 6a, 6b, and 6c received DST, CsA and PGE-1. Cardiac allograft survival of group 2a (PGE-1) was better than that of the control group (9.6 +/- 1.7 days vs. 6.6 +/- 1.9 days) X +/- SD; p < 0.05. Group 4a (DST+PGE-1) had better cardiac allograft survival than group 3 (DST) (20.0 +/- 14.3 days vs. 14.3 +/- 3.3 days, respectively; p < 0.05). Group 6a (DST+CsA+PGE-1) had a better graft survival than group 5 (CsA) but the difference was not significant (44.6 +/ 13 days vs. 37.5 +/- 19.5 days, respectively; p = 0.20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308793 TI - Hypoglycemic effect of plants used in Mexico as antidiabetics. AB - The objective of this work is to investigate the hypoglycemic effect of 12 "antidiabetic" plants used in Mexico. The studies were performed using 27 healthy rabbits with the gastric administration of water, tolbutamide or decoction of the "antidiabetic" plant before the induction of temporary hyperglycemia by subcutaneous injection of 50% dextrose solution (4 ml/kg of weight) at the beginning of the experiment and after 60 min. Blood glucose was determined every 60 min for a period of 5 h. Tolbutamide and eight of the studied plants decreased significantly the hyperglycemia as compared with control test (water) (p < 0.05). The strongest effect was yielded by Guaiacum coulteri, followed by Marrubium vulgare, Crataegus pubescens, Cynodon dactylon, Calea zacatechichi, Buddleia americana, Bauhinia divaricata and Coix lachryma. The decrease of hyperglycemia caused by Physalis phyladelphyca, Pavonia schiedeana and Eucaliptus globulus was not significant (p > 0.05). Urtica dioica increased glycemia slightly. PMID- 1308794 TI - Hodgkin's disease and acute leukemia. Is it a true association? AB - The incidence of secondary malignancy was assessed in 537 patients with Hodgkin's disease treated with radiotherapy (128 patients), chemotherapy alone (156 patients), or in combined modality therapy (253 patients) between January 1973 to September 1985 with a median follow-up of 7.5 years. The dose of radiation therapy, dose of cytotoxic drugs and sequence of treatment was carefully analyzed. No cases of acute leukemia or other secondary malignant disease were identified in these cases. No differences in clinical laboratory features or treatments were identified in relation to previous reports. Racial difference is the unique feature which seems to avoid the development of this complication in patients treated for Hodgkin's disease. We hope that other reports in Latin America can contribute to the identification of race as the difference. PMID- 1308795 TI - Local and systemic antibody response in Balb/c mice immunized with Entamoeba histolytica trophozoites. AB - Several immunization schedules with E. histolytica trophozoites were tested on Balb/c mice in order to induce antibody responses, both in intestinal secretions and in serum. Mice were immunized either orally, systemically, or using one of two combined schedules: the oral route followed by the systemic route (footpad), or vice versa. Each of the immunization schedules used in this project induced an anti-E. histolytica antibody response and there appears to be a correlation between the immunization route employed and the immunoglobulin isotype induced in the gut. Secretory IgA production is favored by the oral administration of trophozoites, whereas mucosal IgG appears to be enhanced by the systemic immunization route. Both schedules are effective in the induction of secretory IgA in the gut, yet higher and earlier levels of IgA appear in orally immunized mice. When systemic immunization is employed, the increase in antibody levels in the intestinal fluid is slower, and IgG is the predominant class. The combined oral/systemic routes of immunization appear to be comparably effective for the induction of local and systemic IgA and IgM antibody production. However, mice immunized first systemically and then locally produce more IgG in both compartments. Combined schedules modify the isotype pattern of antibody responses in serum and in intestinal secretions when compared with single (i.e., oral or systemic) schedules, but they do not appear to favor a secretory IgA immune response. PMID- 1308796 TI - A study of erythropoiesis and iron metabolism in the rabbit in vivo. II. Dependence of the response on iron storage and transport. AB - Rabbits subjected to a daily bloodletting schedule of 10 ml blood per kg body weight increase four- or fivefold their erythropoietic production compared to normal non-bled animals. The maximum response they can reach under these conditions mobilizes more than 9 mg of iron per day per rabbit into hemoglobin. When fed ad libitum with their regular diet, they do not need any further iron supplement for full erythropoiesis. The experimental increment in iron body stores and/or serum iron levels does not enhance their erythropoietic response, demonstrating that iron is not rate limiting under the conditions studied. Furthermore, although serum iron levels are elevated onefold in the controls under chronic anemia with respect to non-bled animals, the concentration of serum transferrin is only slightly increased; hence, the iron saturation of this protein changes from a 50% to an 80% level. In the absence of an extra supplement of iron, rabbits subjected to chronic bloodletting show no signs of body iron depletion, as judged by their continuous macrocytic RBC production. PMID- 1308797 TI - Verapamil does not block the spastic response of Praziquantel on the larvae of Taenia pisiformis. AB - This paper describes that the previous addition of Verapamil does not block the spastic response to Praziquantel (Pz) in larvae of Taenia pisiformis kept in vitro, where opposite results were found in the literature using mammalian tissue. It is possible that Pz stimulates other Ca++ transport channels not sensitive to Verapamil action and promotes Ca++ liberation from calcareous corpuscles stimulating phospholipase C of the tegument surface generating inositol triphosphate. These hypotheses require experimental approaches to define the exact mechanism of action. PMID- 1308798 TI - Hypoglycemic activity of some antidiabetic plants. AB - To assess the hypoglycemic activity mechanism of some plants used empirically by the Mexican population as antidiabetics, traditional preparations of Cucurbita ficifolia, Guaiacum coulteri, Lepechinia caulescens, and Psacalium peltatum, water, tolbutamide, and Regular Insulin were administered to three groups of rabbits each: 1. Healthy rabbits with temporary hyperglycemia induced by the subcutaneous administration of glucose. 2. Rabbits with moderate diabetes (fasting glycemia 150-300 mg/dl), induced with alloxan. 3. Rabbits with severe diabetes (fasting glycemia higher than 400 mg/dl), induced with alloxan. The plant preparations had a hypoglycemic effect similar to tolbutamide in healthy and mild diabetic rabbits and had no effect in severely diabetic rabbits. These results suggest that some pancreatic function or the presence of insulin is required for the hypoglycemic activity of these plants. PMID- 1308799 TI - Plants used by Mexican traditional medicine with presumable sedative properties: an ethnobotanical approach. AB - An ethnobotanical study of plants used in Mexican traditional medicine was made. The source was the national inquiry done by the IMSS-COPLAMAR health program (1983-1985) in which the plants used to treat mental disorders were selected and analyzed, in order to select the most frequent botanical species used in traditional medicine as sedatives, anticonvulsants and hypnotics. PMID- 1308800 TI - Efficacy of pravastatin as a hypolipidemic agent in patients with polygenic hypercholesterolemia. AB - In Mexico, hypercholesterolemia has become a major public health problem particularly in the states of the north of the country and in Mexico City, where a prevalence of 20% has been reported. Schemes of treatment have now been reinforced by the appearance of new cholesterol reducing drugs. The objective of the study was to demonstrate efficacy and safety of a 10 mg daily dose of oral Pravastatin (a new 3-hydroxy-3-methyl glutaryl CoA inhibitor) in a group of patients positive for hyperlipidemia, after 6 months of treatment. Twenty-five patients were included (14 men, 11 women) with an average age of 54 and 50 years, respectively. The main outcome measure was total cholesterol (T-CHOL), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGL), high density lipoprotein cholesterol (HDL-C) and adverse drug reactions report. Twenty-one out of 25 patients completed the study. T-CHOL diminished 21%, LDL-C was reduced by 28%, TGL decreased 6% and HDL-C increased 32%. No adverse reactions were observed throughout the study. Our study shows that the use of a low dose of Pravastatin satisfactorily reduced T-CHOL and LDL-C levels while significantly increasing HDL C after 27 weeks of treatment, without untoward effects. PMID- 1308801 TI - EEG signs of "relaxation behavior" during breast-feeding in a nursing woman. AB - The presence of electroencephalographic signs of "relaxation behavior"; i.e., groups of synchronic, 6-10 Hz, 100-150 microV EEG waves mainly appearing in parieto-occipital regions, have been investigated in a nursing woman during breast-feeding. EEG was recorded once a week from right and left frontal-central, central-parietal, parietal-temporal and parietal-occipital derivations of the mother during breast-feeding of her own child throughout 16 weeks of nursing (from the 4th to the 20th week after delivery). Groups of synchronic 6-10 Hz, 100 150 microV EEG waves were recorded in central-parietal and parietal-temporal derivations, 15-80 sec after starting of suckling of either breast. Proportions of this synchronic EEG activity ranged between 5 to 28% in the central-parietal and 6 to 22% in the parietal-temporal derivations, and significantly higher proportions were found in the right hemisphere. Similarities between EEG signs of "relaxation behavior" elicited by suckling in nursing cats and those elicited by suckling in a nursing woman lead to the possibility that the above described EEG phenomena are an expression of a functional state of the central nervous system which is a part of the integral response involved in the consummatory activity of nursing behavior in women. PMID- 1308802 TI - Osteochondral lesions in developing rats intoxicated with thallium twenty four hours after birth. AB - An i.p. injection of a solution of thallium acetate in deionized water at a dose of 32 mg/kg, in 24-h-old rats, produces morphological and biochemical alterations in both cartilaginous and osseous tissues. From the beginning, there are alterations in the cartilaginous cell as well as in chrondrine, osteoblasts, osseous tissue and bone marrow. Rats were sacrificed at 24, 48, and 72 h and also at 7 days. Two animals survived for 50 days. One showed total irreversible alopecia while the other one had partial alopecia with discrete recovery. Both showed a low weight and a size of 8 cm. Microscopically, degenerative changes were produced consisting of alteration and death of many cartilaginous cells, uneven metachromasia and the chondrine and decrease of the growth cartilage, scanty bone trabeculae with few osteoblasts. The bone marrow showed few myeloblasts and megakaryocytes. Progressive cellular damage throughout the 50 days of survival represents a response of the thallium ionic accumulation and recycling in cellular mitochondria of all the body's cells. This appeared in our study as irreversible and progressive osteochondral alterations with atrophy of the skin and its adnexa, hyalinization of elastic and collagenous fibers with intense interstitial edema. PMID- 1308803 TI - Perinatal prevalence of B hepatitis markers. AB - The present investigation describes the prevalence of markers detected in immunoenzymatic methods, for infection by the hepatitis B virus in sera of mothers and newborn umbilical cord blood in Merida, Venezuela. The sample population was composed of 500 mothers who attended the Obstetrics Department, University Hospital of los Andes, for their delivery between May and October 1990. The global prevalence figure of 11.8% showed a balanced distribution for surface antigen and its antibody. Prevalence for the urban area was 13.49% (RR = 1.49) and 11.80% for mothers from the rural zones (RR = 0.67), 95%, IC 0.63 to 1.9). A statistical difference was found between mothers with two or more live children (14 cases) and those with one or no children (7 cases) for anti-HBs (X2 = 7.62, p < 0.05, RR = 1.43, CI 0.47 to 2.86). Mothers with a history of several sexual partners showed a prevalence of 18.0%, RR = 1.5, CI 0.58 to 2.44, while those who were students, 18.3%, RR = 1.64, CI 0.94 to 2.5. These data may be indicating that sexual transmission mechanisms are of utmost importance, yet more precise investigations are required to confirm this hypothesis. Blood samples from umbilical cord were all negative for surface antigen. PMID- 1308804 TI - Comparative study between the effects of total intravenous anesthesia with propofol and balanced anesthesia with halothane on the alveolar-arterial oxygen tension difference and on the pulmonary shunt. AB - Inhalation anesthesia with halothane, inhibiting hypoxic pulmonary vasoconstriction, causes an increase in intrapulmonary shunt development as well as an increase of alveolar-arterial oxygen tension difference. In contrast, total intravenous anesthesia with propofol, as with other intravenous anesthetics, should not alter pulmonary gas exchange. The present study was carried out using two groups of patients of similar age, sex and weight, who were subjected to neurosurgical procedures. One group was under general inhalational anesthesia with halothane and the other group under total intravenous anesthesia with propofol. In a simple clinical manner and applying established formulae, the determination of intrapulmonary shunt and alveolar-arterial oxygen tension difference showed a significant increase after 120 min in the halothane group, whereas the group that received propofol did not show any significant variation. We therefore conclude that propofol, different from halothane, does not affect the pulmonary gas exchange. PMID- 1308805 TI - Thyroid function and abdominal surgery. A longitudinal study. AB - Surgical trauma produces complex metabolic changes and may be an excellent model for studying the effects of an acute insult on the circulating thyroid hormone concentrations. Abnormalities in thyroid function tests in patients with nonthyroidal illness can be divided into a low T3 syndrome, low T3 and T4 syndrome in more severe cases and elevated T4 syndrome. In this study 30 patients undergoing elective or urgent abdominal surgery were longitudinally evaluated with pre- and postoperative thyroid function tests. Comparing with preoperative values, a significant reduction in total T3 serum values in the immediate postoperative period was seen (p < 0.005). The rest of the variables did not show significant statistical differences between the three periods. Over half of the patients undergoing urgent surgery had a low T3 syndrome, whereas only a sixth of the patients scheduled for elective surgery suffered from this syndrome. In the late postoperative period half the patients submitted to urgent surgery persisted with alterations in thyroid function tests, whereas most of the patients scheduled for elective surgery showed an improvement in their thyroid hormone level in the same period of time. Abnormalities in thyroid hormone metabolism were more frequent in patients admitted for urgent surgery, reflecting the severity of their illness and favoring the concept that these syndromes can be used as prognostic markers. PMID- 1308806 TI - Immune response to parasitic infection in mice without seminal vesicles. AB - A protracted depression of anti-parasitic antibody and DTH responses were observed in Balb/c mice after surgical extirpation of seminal vesicles and ulterior infection with Taenia crassiceps cysts. Inclusion of male seminal accessory glands into the network of immunogonadal interactions was proposed. PMID- 1308807 TI - Capacitation and acrosome reaction of human spermatozoa. An assisted reproduction approach. AB - In this paper we briefly review the recent advances in the understanding of human sperm capacitation, fundamentally focused to give help to the practitioners involved in assisted reproduction. Sperm capacitation has been the subject of study for many years in several animal species, but during the past ten years the advances in assisted reproduction procedures have made important contributions in the progress of this topic in relation to human spermatozoa. In this manuscript we analyze the metabolic, membranal and physiological changes observed in these cells during in vitro capacitation and their relationships with the female genital tract secretions, as well as with the homologous oocytes. PMID- 1308808 TI - Molecular cloning and sequence analysis of the cDNA for northern pike (Esox lucius) growth hormone. AB - The complete nucleotide sequence of the northern pike (Esox lucius) cDNA for pregrowth hormones was determined from clones derived from a pituitary gland cDNA library. Seventeen cDNA clones were isolated from a single mRNA species. A cDNA of 1,227 nucleotides was sequenced and found to encode a polypeptide of 209 amino acid residues, which included a putative signal sequence of 22 amino acid residues. Sequence comparison of the northern pike growth hormone gene to other known growth hormone genes revealed similarities closest to other members of the superorder Protacanthopterygii, which includes the Salmonidae family (i.e., salmon and trout). PMID- 1308809 TI - Characterization of AluI repeats of zebrafish (Brachydanio rerio). AB - Two families of repetitive DNA sequences were isolated from the zebrafish genome and characterized. Eight different sequences were sequenced and classified by two standards, their (G + C) composition and their lengths. For convenience, the sequences were first divided into two types. Type I was (A + T)-rich, was repeated approximately 500,000 times, and constituted approximately 5% of the zebrafish genome. Type II was (G + C)-rich, was reiterated approximately 90,000 times, and comprised approximately 0.5% of the genome. Agarose gel electrophoresis of zebrafish DNA cleaved with AluI revealed three distinguishable bands of repetitive fragments: large (approximately 180 bp, designated RFAL), medium (approximately 140 bp, RFAM), and small (approximately 90 bp, RFAS). The RFAL fragments contained both type I and type II sequences. Limited digestion of genomic DNA indicated that RFAL and RFAM were tandemly arranged in the genome, whereas RFAS showed a mixed pattern of both tandem and interspersed repeated arrangements. Although inclusion of a repetitive sequence in a transgenic construct did not appreciably accelerate homologous integration of transgenes into the zebrafish genome, the AluI sequences could facilitate transgene mapping following chromosomal integration. PMID- 1308810 TI - Automated sequential affinity chromatography of sea urchin embryo DNA binding proteins. AB - An automated method of running a tandem sequence of oligonucleotide affinity columns was used to purify factors that interact specifically with cis-regulatory sites of the CyIIIa cytoskeletal actin gene of the sea urchin embryo (Strongylocentrotus purpuratus). The method allows quantitative enrichment in a single chromatographic run of up to 12 different sequence-specific DNA binding proteins, each of which may then be readily purified to homogeneity by methods such as preparative gel electrophoresis. The affinity chromatography and identification of six different CyIIIa-regulatory factors is described, and the general utility of the method is discussed. PMID- 1308811 TI - A gene encoding chinook salmon (Oncorhynchus tschawytscha) prolactin: gene structure and potential cis-acting regulatory elements. AB - A full-length chinook salmon (Oncorhynchus tschawytscha) prolactin (PRL) gene, the first genomic clone of a teleost prolactin, was isolated and fully sequenced. The chinook PRL genomic sequence spans 6.4 Kb, including 2.4 Kb of 5' flanking sequence, 3.0 Kb representing the five exons and four introns of the complete PRL gene, and 0.9 Kb of 3' flanking sequence. The transcriptional start site of the PRL gene was mapped through the agreement of both primer extension and S1 nuclease protection assay. The 5' flanking region of the PRL gene was searched for potential cis-acting elements based on the consensus binding site of trans acting factor Pit-1, known to be involved in PRL gene expression in mammals. Functional analysis of PRL promoter by the transient transfection of several PRL promoter/CAT chimeric plasmids into rainbow trout pituitary cells suggests a functional PRL promoter whose cell-specific activity is most likely governed by both positive and negative mechanisms. PMID- 1308812 TI - Isolation and sequence analysis of carp gonadotropin beta-subunit gene. AB - Using the cDNA encoding the beta subunit of carp gonadotropin (cGTH-beta) as a probe, 14 clones containing cGTH-beta gene have been isolated from a carp genomic library. Nucleotide sequence analysis indicated that the transcriptional unit of the cGTH-beta gene is 1.2 Kb. Similar to mammalian GTH-beta genes, cGTH-beta gene contains three exons and two introns. The locations of the exon/intron junctions also correspond to those of mammalian GTH-beta gene. Using the primer extension assay, the start site of transcription was determined to be 35 or 37 bp upstream from the translation initiation codon. The TATAA box is present in the 5' flanking region of the gene, 21 bp upstream from the start site of transcription. Three polyadenylation signals, AATAAA, are located in the 3' noncoding region, 111, 430, and 442 bp downstream from the stop codon of translation, respectively. PMID- 1308813 TI - Special issue on transgenic fish. PMID- 1308814 TI - Integration of chromosome set manipulation and transgenic technologies for fishes. AB - Chromosome set manipulation techniques have significant implications for research of transgenic fish. Gynogenesis can be used to generate isogenic lines, to map genes in relation to their centromeres, and to produce fish carrying extra chromosome fragments of foreign origin. Androgenesis can be used to produce isogenic lines and to recover strains from cryopreserved sperm. Triploidy can be induced in fish with heat or pressure treatment of fertilized eggs and by crossing tetraploid individuals with normal diploids. Triploid fish are typically effectively sterile. Triploid interspecific hybrids are usually more viable than the corresponding diploid hybrids. Given concerns about potential reproduction of transgenic fish in the wild, induced triploidy could facilitate application of transgenic technologies in some situations. PMID- 1308815 TI - Fish embryo cell cultures for derivation of stem cells and transgenic chimeras. AB - It has been demonstrated in mammalian systems that techniques using embryonal stem cells provide advantages over conventional injection of DNA into embryos for generation of transgenic animals. We employed cell culture approaches in an attempt to develop this technology for fish transgenesis. Using a trout embryo derived mitogenic preparation in a specialized culture medium, we initiated replication of zebrafish blastula-derived cell cultures and expressed marker genes introduced into the cells by plasmid transfection. Reintroduction of cells from the cultures into blastula-stage embryos indicated that the cultured cells survived and may contribute to the developing organism. PMID- 1308816 TI - Expression of reporter genes introduced by microinjection and electroporation in fish embryos and fry. AB - The technique for foreign gene transfer in fish is becoming a novel method for genetic engineers to produce useful transgenic fish as well as for experimental purposes. Our studies of transgenic fish have been focused on methods of gene transfer and regulatory elements for transgene expression. I describe the characteristics of 3 gene transfer methods we have established (i.e., microinjection into fertilized eggs, microinjection into oocytes, and electroporation). Also described is a series of experiments to estimate activities of several promoters and enhancers in a fish cell line. Finally, experiments to examine activities of the elements shown to be active in the cell line in fish embryos and fry are described. SV2, miw, and metallothioneine promoters of trout and mouse were shown to be active in these experiments. PMID- 1308817 TI - Introducing foreign genes into fish eggs with electroporated sperm as a carrier. AB - A new method has been developed for introduction of foreign genes into fish eggs. The procedure is based on the incubation of fish sperm cells suspended in dilute citrate solution with plasmid DNA, followed by application of high-field-strength electrical pulses (electroporation) to increase DNA binding., uptake, or both. Tissue homogenates and genomic DNA extracts of free swimming fry developed from eggs fertilized with treated sperm was tested to evaluate the efficiency of gene transfer. Dot blot hybridization and gene expression assay demonstrated the presence and expression of the reporter genes introduced in 2.6 to 4.2% of several hundreds of tested larvae of common carp (Cyprinus carpio L.), African catfish (Clarias gariepinus), and tilapia (Oreochromis niloticus). No transgene has been found in the fry resulting from parallel experiments without sperm electroporation. This is the first report on successful application of electroporated sperm cells for production of transgenic fish. PMID- 1308818 TI - No transgenic rainbow trout produced with sperm incubated with linear DNA. AB - We attempted to produce transgenic rainbow trout embryos by fertilizing eggs with sperm incubated with linearized plasmids. One experiment was conducted with the construct pBGH7 in the medium MMSF, with or without DMSO, at 2 concentrations of sperm cells and a relatively low concentration of DNA. The DNA was also in contact with the eggs during insemination and during the first minutes of egg activation. The second experiment was conducted with the construct CMVCAT in the medium MMSF, at 2 concentrations of sperm cells and a much higher concentration of DNA. The DNA was also present during the insemination. DNA analyses and dosages of CAT activity did not permit detection of any transgenic fry. However, one result suggests that sperm cells can capture part of the linear DNA in teh conditions tested. PMID- 1308819 TI - Fish transgene expression by direct injection into fish muscle. AB - The ability of a promoter sequence to drive expression of a reporter gene can be determined by direct injection of copies of the cloned sequence into fish muscle, followed by biopsy of muscle from the site of injection. We describe a set of experiments in which copies of the constructs FV1 and FV2, both comprising a carp beta-actin promoter sequence spliced to the bacterial reporter gene CAT, were injected into the muscle of tilapia fish )Oreochromis niloticus) of between 5 and 8 cm body length. The site of injection was carefully determined so that biopsy samples could be recovered from the injection site 24 hours, 48 hours, and 7 days after injection. Biopsy samples of muscle were homogenized and used for CAT assays. CAT activity was successfully detected in many of the muscle samples. PMID- 1308820 TI - Development of an all-fish gene cassette for gene transfer in aquaculture. AB - To develop an all-fish gene cassette suitable for gene transfer in aquaculture, the antifreeze protein (AFP) gene promoter from the ocean pout (Macrozoarces americanus) was analyzed for its ability to direct exogenous gene expression both in vitro and in vivo. The ocean pout AFP (opAFP) gene promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) was functionally analyzed in two fish cell lines and in Japanese medaka embryos. The opAFP gene promoter was active in these systems, as demonstrated by the transient expression of CAT activity. These results suggest that the opAFP gene promoter is useful for many other gene transfer experiments. To facilitate use of the opAFP gene promoter as a common and versatile vehicle for fish gene transfers, an expression vector, opAFP-V, was constructed by linking the 2.1-kb opAFP gene promoter, the 63-bp opAFP gene 5' untranslated sequence, and the 1.2-kb opAFP gene 3' sequence by two unique restriction sites, Bg/II and HpaI, respectively. Thus, genes of interest can be inserted into either the Bg/II site or the HpaI site depending on the length of their 5' untranslated sequence. The complete DNA sequence of opAFP-V was determined to facilitate future detailed analysis of integration and expression of the transgene. PMID- 1308821 TI - Antifreeze protein gene transfer in Atlantic salmon. AB - Salmonids freeze to death if they come into contact with ice. Many marine fish species that inhabit icy sea waters synthesize antifreeze proteins (AFP) to protect them from freezing. Production of stable lines of freeze-resistant salmon and other species would greatly facilitate development of sea-pen aquaculture in many regions. We successfully introduced winter flounder AFP genes into Atlantic salmon. Research to date indicates stable genomic integration and low levels of expression of winter flounder AFP genes in a small number (approximately 3%) of salmon developed from microinjected eggs. Inheritance of the AFP gene by offspring (F1) from crosses between transgenic and wild-type salmon revealed that the transgenic flounders (F0) were germ-line mosaics. Low levels of AFP precursors could be detected in the blood of all these transgenic offspring (F1). Approximately 50% of the progeny produced by crosses between transgenic F1 and wild-types contained the AFP genes. These results demonstrate that stable germ line transformed Atlantic salmon can be produced. PMID- 1308822 TI - Firefly luciferase gene transmission and expression in transgenic medaka (Oryzias latipes). AB - Plasmids containing the luciferase gene from the firefly (Photinus pyralis) fused to the Chinese hamster metallothioneine I promoter (ChMTI) were microinjected into the pronuclei of medaka (Oryzias latipes) eggs, which were then artificially inseminated. Evidence of integration into the genome was gained from observation of germ-line transmission in a mendelian fashion from the F1 to the F2 generation. However, gene expression (light emission) could not be demonstrated in the established transgenic line. In a separate program, transient expression of gene constructs containing the luciferase gene fused to various promoters was compared in medaka embryos. Plasmids were microinjected into pronuclei, and homogenates from 3-day-old embryos were measured for light emission using a luminometer. Among the various promoters tested (SV40, RSV-LTR, ChMTI, HSP70, and mouse albumin), the highest levels of luciferase gene expression were observed in gene constructs containing ChMTI and HSP70 gene promoters. Expression in these two constructs was significantly increased following administration of ZnSO4 or heat treatment, respectively. Plasmids were also introduced into goldfish fibroblast-like cells in vitro, in which enzymatically active luciferase was transiently expressed. Assaying for expression of luciferase provided a rapid and sensitive method for monitoring promoter activity. The potential usefulness of this fish species for cancer research is discussed based on accumulated information from carcinogenesis studies. PMID- 1308823 TI - Selection of promoters for gene transfer into fish. AB - A variety of gene constructs containing carp beta-actin regulatory sequences were tested for their ability to drive transient expression of the chloramphenicol acetyltransferase reporter gene in 3 fish cell lines: carp epithelial cells (EPC), rainbow trout hepatoma cells (RTH149), and rainbow trout fibroblasts (RTG2). The constructs showed a wide variation in their levels of expression, and there were significant differences in the effects of transcriptional elements in the 3 cell lines. Sequences that enhanced expression in EPC cells were inhibitory in RTH149 and RTG2 cells. All cell lines exhibited the presence of nuclear trans acting factors that could bind to implicated transcriptional control elements. On the basis of the cell culture results, selected constructs were examined for activity in early carp development. Constructs active in embryos and fry were further tested and found to express transgenes in adult fish. PMID- 1308824 TI - Medaka as a model of transgenic fish. AB - The medaka (Oryzias latipes) is an egg-laying fresh-water fish. We describe the medaka as a model system of transgenic fish in germs of biological characteristics, manipulation of embryos, gene expression in development, and basic research in aquaculture. The fish are small (approximately 3 cm in length) and have a short generation time (approximately 3 months). The eggs are easy to manipulate. A foreign gene (e.g., the chicken delta crystallin gene) is transferred and expressed stage-dependently in development of medaka embryos. Growth hormone genes of vertebrates are transferred and expressed and, in some cases, accelerate growth of the fish. Thus, the medaka is one of the most promising models of transgenic fish for basic research of gene expression and aquaculture. PMID- 1308825 TI - Fish gonadotropin-releasing hormone gene and molecular approaches for control of sexual maturation: development of a transgenic fish model. AB - The prepro-GnRH gene and mRNA primary structure were fully established from Atlantic salmon (Salmo salar) and partially from rainbow trout (Oncorhynchus mykiss). Results show that the GnRH coding region of 30 base pairs is well conserved during evolution. In contrast, the GnRH-associated peptide (GAP) sequence shows very limited homology when the GnRH genes from mammalian and teleost species are compared. A simple method for selecting transgenic fish after transfer of the firefly luciferase gene was developed. The method involves bioluminescent measurement of live animals in a scintillation counter. PMID- 1308826 TI - Transfer, expression, and inheritance of salmonid growth hormone genes in channel catfish, Ictalurus punctatus, and effects on performance traits. AB - We examined expression and inheritance of salmonid growth hormone genes RSVLTR rtGH1 cDNA and RSVLTR-csGH cDNA, transferred to channel catfish (Ictalurus punctatus) by microinjection. One to 9 copies of the foreign DNA were inserted in either head-to-tail tandem array at single insertion sites or single copies at multiple insertion sites. All P1 transgenic catfish evaluated produced salmonid growth hormone regardless of the construct. Five P1 x P1 matings were accomplished. The spawning rate and fertility of these P1 transgenics in artificial spawning conditions were comparable to those of normal channel catfish. In two of three years, 100% spawning and 100% hatch were obtained. Percent transgenic progeny observed in the five matings were 20, 52, 7, 47, and 0%, which was lower (P < 0.001, chi 2) than the 75% inheritance expected assuming the P1 brood stock had at least one copy of the foreign gene integrated and were not mosaics in the germ line. At least 7 of 10 P1 were mosaics, and a minimum of 2 of 10 P1 did not possess the salmonid growth hormone genes in their germ line. P1 transgenics grew at the same rate as their nontransgenic full siblings, which is not surprising because the P1 were mosaics. F1 transgenic progeny in two families possessing RSVLTR-csGH cDNA grew 26% faster, to 40 to 50 gm, than their nontransgenic full siblings when evaluated communally. One F1 progeny group produced by RSVLTR-rtGH1 cDNA x RSVLTR-csGH cDNA mating and one F1 progeny group (parents either RSVLTR-rtGH1 cDNA or RSVLTR-csGH cDNA) grew at the same rate as normal full siblings when grown communally to 25 gm and 60 mg, respectively. In families where F1 progeny grew faster than controls, the range in body weight and coefficient of variation for the transgenic full siblings were less than those for controls. In families where F1 progeny grew at the same rate as controls, range in body weight and coefficient of variation were similar for transgenic and normal individuals. The percent deformities observed in P1 transgenics (13.6%) was higher (P < 0.05) than in microinjected P1 nontransgenics (5.1%). Percent deformities in transgenics and control F1 channel catfish was not different (p > 0.05; 0.5 and 2.8%, respectively). PMID- 1308827 TI - Validation of new technology for antibody detection by antiglobulin tests. PMID- 1308828 TI - The MAIPA assay and its applications in immunohaematology. AB - The monoclonal antibody immobilization of platelet antigens (MAIPA) assay has proved to be a reliable and useful tool in platelet immunology. After immunochemical localization of the most important platelet allo- and autoantigens on platelet glycoproteins (GPs) IIb/IIIa, Ia/IIa, Ib/IX, the corresponding antibodies can easily be detected with this technique because mAbs against these membrane constituents are now readily available. The assay also allows reliable typing of platelet alloantigens. Detection of GP-specific PAIgG (by direct MAIPA) has proved to be a specific diagnostic sign of AITP. The MAIPA assay allowed identification of 'new' alloantibody specificities including alloantibodies against 'low-frequency' antigens. The principle of this technique has successfully been applied to characterize antibodies against lymphocytes, endothelial cells and granulocytes. PMID- 1308829 TI - Analysis of fresh frozen plasma administration with suggestions for ways to reduce usage. AB - A programme for the daily monitoring of Fresh Frozen Plasma (FFP) usage, combined with continuous education in the correct use of FFP, was started at William Beaumont Hospital in 1985. In 2 years, this had resulted in a 77% reduction in FFP usage. An analysis of the type of cases which received FFP, after the major reduction had occurred, from July, 1985 through June, 1989 is presented. During this time 2,612 units were administered to 873 patients, an average of 54 units per month. According to the accepted criteria established by the Hospital Transfusion Committee, 67% of the transfused units on the medical service were deemed indicated, compared with 54% on the surgical service. Most of the FFP was used to treat patients with liver disease, or receiving coumadin, or undergoing coronary bypass surgery. Conditions which will decrease the need for FFP administration are also presented for consideration. The results indicate that a consistent monitoring and education programme can keep blood and blood component usage at a defensible minimum. PMID- 1308830 TI - Transfusion-associated graft-versus-host disease in patients with Hodgkin's disease and T cell lymphoma. AB - Two patients, one with Hodgkin's disease and one with peripheral T cell lymphoma, developed transfusion-associated graft-versus-host disease 16 and 8 days after transfusion of red cell and platelet concentrates. Fever and skin rash were followed rapidly by an elevation of liver enzymes and the onset of diarrhoea and pancytopenia. Despite treatment with high-dose methylprednisolone and anti lymphocyte globulin, commenced within 7 and 2 days of the onset of rash, grade IV GvHD persisted and both patients died with severe pancytopenia. HLA types of peripheral lymphocytes of the patient with Hodgkin's disease were inconsistent with those of her parents and siblings, but HLA typing of her fibroblasts revealed that her true type was consistent with those of her parents and that her circulating lymphocytes were not genetically her own. The HLA types of the patient with T-cell lymphoma were inconsistent with those of her siblings which suggests, but, in the absence of other evidence, does not prove, chimaerism. PMID- 1308831 TI - Platelet counting using plasma platelet concentrate samples. AB - Platelet counting using samples of plasma from platelet concentrates prepared for transfusion was assessed. The methods employed included a manual phase-contrast method, and counting with Coulter S Plus and Sysmex E-2500 counters. All methods were reproducible (mean CV of 4.9, 2.2 and 1.4%, respectively). However, neat samples of platelet concentrates analysed by Coulter counter were inaccurate (mean count of 863.8 x 10(9)/l compared to 1018.9 x 10(9)/l counted manually). Moreover, the Coulter platelet counts were non-linear above 900 x 10(9)/l, whereas the E-2500 platelet counts were linear to 2700 x 10(9)/l. A one-in-three pre-dilution was required to obtain accurate, linear counts with the Coulter counter, whereas the E-2500 was accurate without pre-dilution (mean count of 1030.2 x 10(9)/l compared to 1018.9 x 10(9)/l counted manually). In conclusion, the method of platelet counting may affect true platelet yields. PMID- 1308832 TI - Immunomodulatory activity of different blood products on the mitogen-induced human lymphocyte transformation. AB - Blood transfusions have an immunosuppressive effect on the recipient and induce changes in several immunological parameters. We studied the effect of homologous and autologous fresh plasma (FP), fresh frozen plasma (FFP), heparinized plasma, as well as the influence of red blood cells (RBC), CPDA-1, CPD, heparin, PAGGS mannitol, SAG-mannitol and ADSOL on mitogen-induced lymphocyte transformation. Both homologous and autologous FP and FFP decreased the PHA and ConA response of human lymphocytes (P < 0.05). The PWM response was reduced by FP (P < 0.05). The mean t1/2 of plasma-induced suppression was approximately 38 h. Dose-dependent suppression rates were observed with pure CPDA-1 and CPD solutions. In contrast, heparinized plasma showed an elevated PHA- and ConA-induced transformation rate (P < 0.025), whereas PWM induction was unaffected. In addition, washed RBC, pure PAGGS-M, SAG-M and ADSOL solutions revealed no effect on the PHA response. Freezing, heating or recalcification of plasma resulted in an increase in the PHA response. Adenine was not immunosuppressive in vitro. We conclude that, in addition to unspecific mechanisms by CPDA-1 or CPD, an unknown plasma factor, which is susceptible to changes in temperature or storage conditions, suppresses the PHA-, PWM- or ConA-induced T-cell immune response. Further clinical studies are needed to correlate these observations with clinical phenomena. PMID- 1308833 TI - Development, optimization and use of an enzyme linked immunosorbent assay (ELISA) to measure factor VIII antigen utilizing monoclonal antibodies. AB - An enzyme linked immunosorbent assay (ELISA) has been developed to measure VIII:Ag in plasma and concentrates. The assay utilizes two commercially available monoclonal antibodies to VIII:Ag and provides an alternative to the established immunoradiometric assay (IRMA). It has the advantage of not requiring the use of radioactive material and human antibodies. The assay sensitivity is 0.006 u/ml and the interassay coefficient of variation is 6.3%. Forty-eight samples with VIII:Ag levels ranging from 0.006 to 1.5 u/ml were assayed by both ELISA and IRMA. The coefficient of correlation between the two assays was 0.89. In addition to measuring human VIII:Ag, it is also possible to detect antigen in several animal plasma and sera. PMID- 1308834 TI - Audit of the use of packed red blood cells in association with seven common surgical procedures. AB - The risks and costs associated with the transfusion of blood and its components have led to increasing demands for evidence of the appropriate use of blood components. We have examined the use of packed red blood cells (PRBC) in association with seven common, surgical procedures performed in 1987 and 1988 to establish patterns of use. The information has formed the basis for surgical blood order schedules and autologous donation targets for these procedures. It has also been used to determine appropriate audit 'triggers' and the results of an audit using these 'triggers' are reported. PMID- 1308835 TI - A survey of cold-growing gram-negative organisms isolated from the skin of prospective blood donors. AB - The skin of the antecubital fossae of 90 subjects, chosen at random but eligible to be blood donors, was sampled using sterile swabs. This sampling was done prior to disinfection. The swabs were inoculated into a selective culture medium and 'incubated' at blood bank refrigerator temperature for a total of 6 weeks. The results show that there were a number of cold-growing Gram-negative bacilli (GNB) on the skin tested. One of the GNB carriers found was subjected to frequent testing both before and after skin disinfection. The routine skin disinfection regime for blood donors was used in an attempt to establish its effectiveness. Despite regularly being able to culture Pseudomonas fluorescens prior to swabbing, no swabs taken after disinfection showed growth. This volunteer was subjected to a skin biopsy to establish whether the skin disinfection might be simply superficial. No growth occurred in the medium into which biopsy tissue, after disinfection, was inoculated. We conclude that although GNB may be present on donors' skin, the disinfection procedure, as used by us prior to donation, was effective. PMID- 1308836 TI - Western blotting for HIV-antibody confirmation in blood donors: an improved approach by recombinant immunoblots. PMID- 1308837 TI - Alloimmunization to platelet antigen HPA-1a (Zwa): association with HLA-DRw52a is not 100%. PMID- 1308838 TI - Pulmonary embolism in Ibadan, Nigeria: five years autopsy report. AB - The autopsy findings and clinical features in 60 patients with fatal pulmonary embolism (PE) in University College Hospital, Ibadan, between 1985 and 1989 are analysed in the current study. Pulmonary embolism occurred in 3,8 pc of all autopsied patients during this period. There was a male to female ratio 1,4 to one and average age was 47 years. Malignant neoplasms, infections and cardiac failure were the leading predisposing factors to PE identified. The ante-mortem clinical features consisted largely of non-specific respiratory symptoms of dyspnoea, cough, chest pain and haemoptysis. Of these patients, 15,6 pc were diagnosed ante-mortem as having PE. Pulmonary infarction occurred in 13,3 pc of the cases and was commoner in females and in patients with underlying cardiac diseases. This study emphasises the need for a high clinical index of suspicion to improve the antemortem diagnosis of this potentially fatal condition and to advocate a greater use of prophylactic anti-coagulant therapy in high risk patients. PMID- 1308839 TI - The effects of Cassia abbreviata on rat blood pressure. AB - The effects of a crude extract of the stem bark of Cassia abbreviata on mean arterial pressure in anaesthetized rats were investigated. Bolus injections of the stem bark elicited a transitory fall in blood pressure which was dose dependent. The depressor response was not blocked by atropine nor propranolol thus indicating that muscarinic and beta 2 receptors are not involved. However it was partially blocked by diphenhydramine, and H1 antagonist. The latter also partially blocked the depressor response to histamine which is mediated partially through both H1 and H2 receptors. It is concluded that the stem bark of C. abbreviata contains histamine or a chemically related substance and that it is this component which is responsible for lowering the blood pressure. PMID- 1308840 TI - Cutaneous squamous cell carcinoma in Tanzania. AB - The Tanzania Cancer Registry at Muhimbili Medical Centre, Dar es Salaam, Tanzania was reviewed for squamous cell carcinoma of the skin in non-albino African subjects. The data was analysed for age, sex, site and predisposing factors. Our results were then compared with studies previously carried out in Tanzania, elsewhere in Africa and also on Blacks in America. Squamous cell carcinoma of the skin was found to be a common malignancy, and the commonest skin cancer. Its peak was in the 40-49 years age group though it could occur in children under five years of age. The most affected site was the lower limb, followed by the head and the neck. The penis in the male and the vulva in the female were the third most affected sites. The scalp and the lip were more affected in females than males. Chronic trauma, chronic ulcers, and scars were the main predisposing risk factors to the lower limb and the scalp, while ultra violet radiation to the head and neck, and smegma of the uncircumcised penis were thought to be predisposing risk factors. PMID- 1308841 TI - [The time of depression. Cyclic time and linear time]. PMID- 1308842 TI - Seasonal vulnerability to depression. Implications for etiology and treatment. AB - The risk for depression increases at two opposite times of the year--late spring/early summer and late fall/early winter. In 15% of patients with recurrent major depression, depressive episodes regularly recur on an annual basis in one of the two seasonal risk periods. Thus, there are primarily two forms of seasonal affective disorder: recurrent fall-winter depression and recurrent spring-summer depression. The opposite seasonal types of depression tend to have opposite vegetative symptoms. Sleep, appetite and weight increase in winter depression and decrease in summer depression. An important implication of the seasonality of depression is that some type of depression may be caused by changes in the physical environment and that manipulations of the physical environment may be used as treatments. There is now extensive evidence that exposure to bright artificial light is an effective treatment of recurrent winter depression. A corollary is that seasonal deficiency of natural light probably induces winter depression. There have been considerable efforts to elucidate the biological mechanisms of winter depression and its response to phototherapy. Although no single system has been shown to be responsible for the syndrome, there is evidence that the indole hormone melatonin, the indole neurotransmitter serotonin, and the peptide neurohormone corticotropin releasing hormone (CRH) play roles in the pathophysiology and phototherapy of winter depression. PMID- 1308843 TI - [The depressive patient before depression]. AB - This paper describes five prototypes of depression which develop from different temperamental substrates: timid-inhibited, dysthymic, hyperthymic, cyclothymic and irritable. They correspond, respectively, to anxious depressions, double depressions, anergic depressions, rapid-cycling depressions, and hostile depressions. The author argues that, despite a certain degree of overlap in pharmacologic response, each prototype has a relatively unique profile, including benzodiazepines, MAOIs, SSRIs, TCAs, lithium, low dose neuroleptics and anti epileptic agents. PMID- 1308844 TI - [Time and the depressive subject]. AB - Dealing with the diseased man means dealing with man, and whether his disease be organic or psychic, this disease is, first and foremost, a human affliction imposed by life. Any attempt at understanding this affliction should first answer the question of what "being a man" signifies. When Nietzsche writes that man is an animal "not yet established", "an afflicted animal", one may understand that man is afflicted by himself and that he is not a man in the way a thing is a thing. Our approach is based on a phenomenology of existence which focuses on the style of existence of the concrete individual rather than on the supra-individual features of psychopathological syndromes. Actually, depressive conditions exist in all cultures and at all ages; this reality is as intimate to man as is his relation with time. In the common experience of our "good" and "bad" days, we are often unaware of time that passes or, on the contrary, we feel that time is sluggish and we discover two things. First, as shown by E. Straus, we experience two forms of time: a time of the Ego moving along with our own history and a time of the world which is a time we share with other men and with things. Depression has its roots in the discrepancy between these two forms of time. Besides, this experience shows that everything we do during our daily life can be withdrawn. We experience a loss, not of an object that disappears but of our feeling, of our contact with the ambient world.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308845 TI - [Time and depression in children and adolescents]. AB - The existence of depression in young individuals has often been denied or at least underestimated particularly during adolescence, to the benefit of such other concepts as morosity, inherent in this period of life, and from which depression should be differentiated. Recent epidemiological investigations in the general population have revealed an approximate 2% and 10% prevalence of depression in the child and the adolescent, respectively. This considerable increase in morbidity is associated with a modification of the sex ratio: more boys are affected before puberty, more girls after puberty. In the present work we shall first deal with the semiology and comorbidity of depression as related with the developmental changes occurring in the child and the adolescent. Thus, several studies have shown that the DSM III criteria for affective disorders are consistently applicable to pre-puberty children and adolescents as well. However, depression in the pre-puberty children may be more ostentatious, manifesting itself by psychomotor agitation, somatic complaints and anxiety comorbidity of the type: Separation Anxiety Disorder and phobias. Depressed adolescents may exhibit more anhedonia, more depressive cognition, hypersomnia, weight variations, more alcohol or drug abuse and suicide attempts, and, in one third of them, greater coexistence of anxiety disorders or behavioural disorders. The course of depression at this age is now known, owing to catamnestic studies that proved methodologically satisfactory (we personally managed the follow-up of 75 depressed adolescents over an average 45 months). Depression in the child and the adolescent is not a benign affection, it is a long-lived, recurrent and disabling illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308846 TI - [Depression in middle age patient]. AB - "Middle age of life" should be considered more as a psychological concept than a chronological one. It may be defined very roughly as the forties but the limits are variable within the age range 35-50 years. This period is often one of existential crisis marking the access to the age of maturity. This "transition", or "maturescence", confirms or modifies life orientations previously selected by the subject according to modalities that are sometimes difficult to live and assume, hence the frequency of depressions. Among internal modifications, there is an important change in the way time is lived; from then on, the subject becomes clearly aware of his past lifetime and of his remaining lifetime. Time has come for him to draw a balance, which involves looking at himself from a distance, interrogating himself about his previous choices, a feeling of confinement, often a relative degree of disillusion. The subject must discover for himself a new form of presence in the world. In parallel, the members of his family environment also change: parents become old, adolescents develop their social autonomy, husband or wife follows his/her own existential route in an individual mode. All such modifications often promote a loss of the subject's usual landmarks, a relative degree of puzzlement, sometimes even a destruction of pre-existing harmony that may impair the psychological balance of the subject. Promoted by anxiogenic conflicts due to changes, depressions frequently occur in the middle-age group, depending on the above fragilizing factors, the particular circumstances, and the subject's background.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308847 TI - [Depression and aging]. AB - Old age is a qualitative state during which depression frequently occurs. This illness presents particular features which should be considered in the course of both normal ageing and senility. Viewed as an existential crisis, ageing may be considered as a depression promoting factor. Rich in depression promoting factors, this period of life is a sequence of crises which result in reorganizations heavily dependent on the adaptive capabilities of the aged person. During ageing, depression exhibits particular features that one should be able to recognize and distinguish from the consequences of deficits that are the normal adjuncts of the ageing process. The same is true of alterations occurring in the cognitive sphere and which might result from demential alteration. During ageing, depression should be identified among the other decompensation patterns occurring in the aged patient by viewing the situation in terms of overhelmed mechanisms. Depression exhibits a pattern whereby it relates closely with the risk of dementia. Therapeutic management should take into account such a perspective, that one might call transnosographic, when considering the depressiveness of aged patients as a high-risk situation requiring long-term follow-up of their biological, psychodynamic, social and cognitive functions. PMID- 1308849 TI - Features of recurrent brief depression. AB - Recurrent brief depression, characterised by frequently occurring brief depressive episodes, lasting less than two weeks, is now recognised as a common and disabling illness with a chronic relapsing course and a significant suicide risk. The episodes have a mean duration of 3 days, but otherwise fulfill the symptomatic criteria for DSM III-R major depression. Some two thirds of episodes satisfy severity criteria for at least moderate depression and about a third for severe depression. They recur erratically with a mean period of 18 days between the start of one episode and the next. Because of the frequency of the episodes patients may report longer continuous periods of depression than was the case and may be mistakenly perceived as dysthymia as major depression. It is important to identify these patients as treatment response appears to differ. The episodes are too short to be able to assume efficacy with conventional antidepressants; it is necessary to adopt a prophylactic strategy for treatment aiming to reduce the severity, the frequency, or the duration of episodes. PMID- 1308848 TI - [Duration of antidepressive treatments]. AB - In spite of the considerable amount of research undertaken in the field of biological psychiatry, there is currently no reliable guide allowing us to predict with accuracy the response of a patient to an antidepressant treatment. Moreover, owing to the heterogeneity of the spectrum of affective disorders, to the importance of eliminating the various factors involved in an apparent resistance to an antidepressant therapy, it seems aleatory, particularly for an individual patient, to foresee precisely the length of an antidepressant treatment, except may be in unipolar disorders. The quality of the physician patient therapeutic relationship should never be neglected. The recent hypotheses pertaining to the etiopathogenesis of affective disorders, the advent of new psychotropic agents such as the specific serotonin uptake inhibitors, or other agents not acting through this mechanism and the MAOI, type A, as well as the utilization of corticosuppressor drugs, may pave the way to new therapeutic avenues that could, in the future, modify the prognosis and the duration of the treatment of the depressive affective disorders. PMID- 1308850 TI - From enzyme to enzyme & protein. PMID- 1308851 TI - In vitro inhibition of alkaline phosphatase activities from intestine, bone, liver, and kidney by phenobarbital. AB - A kinetic study of the inhibition of several alkaline phosphatase (AP isoenzyme activities by phenobarbital was carried out using p-nitrophenylphosphate (10 mM) as a substrate at pH 9.8 in a 300-mM Hepes buffer. AP from bovine kidney, calf intestine, bovine liver, and rat bone was used. Over a phenobarbital concentration range of 20-400 mM, all these isoenzymes were inhibited in an uncompetitive manner with a Ki of 200 mM for intestinal AP, and in a linear mixed type manner for all the other isoenzymes tested. The Ki values were 10, 40 and 55 mM for kidney, bone and liver AP, respectively. The use of 15 mM carbonate bicarbonate or 400 mM diethanolamine buffer did not modify the degree of inhibition of intestinal AP activity. Dixon plots of the reciprocal of reaction velocity versus inhibitor concentration either at different substrate concentration or at different DEA concentration indicate uncompetitive inhibition for the intestinal enzyme. This in vitro inhibitory effect of phenobarbital is in contrast to its in vivo stimulating action on AP. However, in the whole animal, the effects of phenobarbital administration probably represent the sum of multiple effects. PMID- 1308852 TI - Alkaline phosphatase and phosphotyrosine phosphatase activities of cultured amniotic cells with trisomy 18. AB - In cultured amniotic cells from fetuses with Edward's syndrome (trisomy 18), the activities of two protein phosphatases, alkaline phosphatase and phosphotyrosine phosphatase, were measured. Comparison with normal fetal cells showed a different behavior for each enzyme. Alkaline phosphatase was significantly lowered while phosphotyrosine phosphatase remained at normal levels. The interest of these enzyme assays in the screening procedure of this severe chromosome defect is discussed. PMID- 1308853 TI - Purification and characterization of 6-pyruvoyl tetrahydropterin synthase from human pituitary gland. AB - 6-Pyruvoyl tetrahydropterin synthase, the enzyme that catalyses the conversion of 7,8-dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, was purified 3,330-fold from human pituitary gland with an overall recovery of 30%. The native enzyme has a molecular mass of 68 kD and consists of four identical subunits of 16.5 kD. The pH optimum of the enzyme in Tris/HCl buffer is 7.5. The enzyme is dependent on Mg2+ and NADPH and has a Michaelis-Menten constant of 10 microM for its natural substrate, 7,8-dihydroneopterin triphosphate. The isoelectric point of the human enzyme is 4.3-4.6. The human pituitary gland enzyme is heat instable in contrast to the enzymes from human, rat and salmon liver, and Drosophila head. The amino acid composition showed remarkably high content of acidic amino acids Asp and Glu. The N-terminus was found to be blocked. PMID- 1308854 TI - A new continuous optical assay for maltase and sucrase. AB - A new method for the assay of maltase and sucrase is reported. The method makes use of mutarotase, hexokinase and glucose 6-phosphate dehydrogenase as ancillary enzymes. The reaction is linear at least up to a delta E/min of 0.13. PMID- 1308855 TI - Pathological release of urinary endopeptidase 24.11 early after renal transplantation. AB - Endopeptidase 24.11 (EC 3.4.24.11) enzymatic activity was spectrofluorimetrically measured in human urine, using a synthetic peptidic substrate. Urinary endopeptidase 24.11 output (Uendo) was determined in 24-hour urine samples of 10 kidney transplant recipients during the first 2 weeks after surgery. In 9 patients, a large increase in Uendo levels was noted during the 1st and/or the 2nd postoperative days (mean +/- SEM of peak Uendo 624 +/- 122 micrograms/24 h, p = 0.0003 as compared to 239 +/- 20 micrograms/24 h in a healthy control population). This occurred whether patients received OKT3 (n = 6) or cyclosporine A (n = 3) as primary immunosuppression. Uendo returned to normal between the 3rd and the 5th postoperative day. We conclude that renal transplantation is associated with an early and marked release of endopeptidase 24.11 in urine. This could be due to the potentially toxic effects of ischemia and/or immunosuppressive drugs on the proximal tubular epithelium. The clinical usefulness of urinary endopeptidase 24.11 as a marker of tubular injury remains to be assessed. PMID- 1308856 TI - Sex and age dependence of rat kidney sialidase. AB - Rat kidney sialidase levels have been reported to be markedly altered in pathological states such as diabetes. This was associated with a modification of sialic acid levels. Therefore, it was interesting to study the variations of kidney sialidase and sialyltransferase activities and sialic acid content according to sex and age. This was carried out from birth to 210 days of age. The substrates used were sialyl alpha(2-3)[3H]-lactitol for sialidase activity, asialofetuin and [14C]-CMPNeu5Ac for sialyltransferase activity. In males sialidase activity increased until 32 days then slightly declined. In females, the activity increased and leveled off at 135 days of age. Higher sialidase activity was observed in females than in males from 56 days of age. Gonadectomy had no effect on this activity. In both sexes, sialyltransferase activity decreased markedly with age. This activity was higher in females than in males, whereas sialic acid levels varied only moderately with age and were slightly higher in females. PMID- 1308857 TI - Urinary cholinesterase activity is increased in insulin-dependent diabetics: further evidence of diabetic tubular dysfunction. AB - We measured the cholinesterase activity in morning urines from 63 insulin dependent diabetics and 27 controls. The total esterase (TotE) activity (Ellman's method) has been divided into aliesterase (AliE), pseudocholinesterase and acetylcholinesterase by means of two inhibitors, eserine and quinidine. Diabetics were divided in 2 groups according to the urinary albumin/creatinine ratio (mg/mmol, < 2 in group 1, > 2 in group 2). The urinary cholinesterase behavior was correlated with that of a known tubular lysosomal hydrolase, N-acetyl-beta-D glucosaminidase (NAG). Compared to normals, in addition to a significant increase in urinary NAG in diabetes (in group 2 more than in group 1), TotE and AliE were also significantly raised (+36% and 109% of the controls, in group 1 as much as in group 2). PMID- 1308859 TI - [ Basic principles in organizing a service of "Occupational medicine"]. PMID- 1308858 TI - Essential fructosuria: increased levels of fructose 3-phosphate in erythrocytes. AB - Erythrocytes of 3 adult siblings with essential fructosuria contained 45-200 mumol/l fructose 3-phosphate (Fru-3-P), i.e. 3-15 times the concentration in normal controls. Sorbitol 3-phosphate was also increased, but to a lesser degree. An oral load with 50 g of fructose produced an additional 40 mumol/l increase of erythrocyte Fru-3-P after 5 h. The rate of Fru-3-P formation by red cells in vitro was normal. HbA1 and HbA1c were normal. The suspected pathogenetic role of Fru-3-P in diabetic complications is questioned. PMID- 1308860 TI - [Problem of controlling current mental capacity in operators]. AB - The industrial means to control and forecast the current mental capacity of operators are absent nowadays in spite of its level connected with about 2/3 of accidents through the personnel's fault. Results of 10 year-experience show how the computerized self-educating adaptable systems of current individual mental capacity monitoring in power engineering operators were created. The systems to control the mental capacity in operators before and over the course of the shift let also improve the reliability and economy in exploitation of huge technological enterprises and preserve the operator's health. PMID- 1308861 TI - [Characteristics of work intensity and fatigue in proof-readers in the polygraphic industry]. AB - A group of proof-readers showed the elective resistance to fatigue from visual work by the end of working shift. Changed near point, decreased power and hardiness of the hand, aggravated self appraisal were more significant than altered achromatic visual stability, time of motor response to the light and critical flicker fusion frequency. The studied parameters were compared making use of Derevianko's index. PMID- 1308862 TI - [Health status and prevention of disorders in people performing intensive visual work]. AB - Electronic industry workers, whose work involves visual strain were examined. The work appeared to be characterized by a plenty of unfavourable factors: high visual and emotional intensity, considerable strain of the locomotor apparatus in supporting a fixed sitting posture. The micromountain workers were exposed to poor ionized and ozonized air conditions combined with high bacterial contamination and lack of the UV rays in the air. Examinees showed markedly changed health and functional status of the main body systems. A complex of hygienic, prophylactic, physiological, technological and medical measures yielded remarkable results. Working conditions of electron industry workers are to be regulated. PMID- 1308863 TI - [Changes of functional state of the human body and the dynamics of its recovery in hard physical work in protective devices in various air temperatures]. AB - Effect of the hard manual work on humans using the individual protective means in temperature conditions from 17 to 30 degrees C was studied. The investigation revealed the altered thermoregulatory, circulatory, central nervous systems and the acid-base status. The changes were found depending on the environmental temperature. The recovery period (one-hour rest and shower) did not normalize the disordered functions, so further correction of the functional status is necessary. PMID- 1308864 TI - [ Dynamics of NAD-dependent isocitrate dehydrogenase activity in homogenized rat liver exposed to toxic products of the phosphorus industry]. AB - Dynamic studies showed that the combined action of phosphine and hydrofluoric acid damages the Krebs cycle reactions, dehydrogenization of isocitrate and synthesis of citrate in homogenized rat liver. Yellow phosphorus harmed the citrate synthetic reaction of citric acid cycle in homogenized rat liver as well. That activated the alternative action principles in the cycle. The main cause of such disorders in the Krebs cycle in likely to be the abnormal fat metabolism induced by toxic products of phosphorus industry. PMID- 1308865 TI - [The making of the industrial physician]. AB - A total of 259 questionnaires distributed among physicians working at plant shops were analysed. The formation of such specialist turned out to be difficult because of inadequate training in occupational pathology and hygiene at the medical institute. PMID- 1308866 TI - [Predicting the toxicity level of organic substances by analyzing their structural fragments]. PMID- 1308867 TI - [The main principles in the combined action of metals and their significance for hygiene]. AB - Features of metal's co-action according to the results of toxico inetic studies concerning the binary elemental combinations infused into the body are discussed. The investigations revealed that the stoichiometric laws of metals' co-action depended on the way the metals were infused by and the scheme of their combined action, on their qualitative and quantitative composition. The quantitative changes in the metabolism of metals during their co-action were found the most important. These changes may serve to evaluate and forecast the combined action of metals. The role of individual metallic qualities in their metabolic co-action was proved to be important. PMID- 1308868 TI - [Role of psychological studies in clinics for occupational diseases]. AB - The authors emphasize the significance of psychological studies in patients with occupational diseases. Foreign and home investigations of the problem are reported. The programme and prospects for the introduction of the methods into practical medicine are presented. PMID- 1308869 TI - [Health disorders in workers of the fish processing industry]. AB - The contributors propose a study of the labour conditions (microclimate, work load and intensity) in processing of dried yellowfin fish, describe results of the psycho-physiological and clinical studies, including medical examinations, epicutaneous testing, ventilation capacity of the lungs and peripheral blood laboratory studies. It was established that the technological processes of drying yellowfin fish exhibited exposure to the biological factors causing irritations and sensibilization of the skin fraught with occupational diseases (dermatitis) and respiratory disorders (allergic rhinopathy and the pre-asthma syndrome). PMID- 1308870 TI - [Gas chromatography evaluation of metacrylonitrile in the air of the work area]. PMID- 1308871 TI - [Occupational morbidity of oil industry workers on the mainland and continental shelf]. AB - Data of occupational morbidity in oil industry workers of Azerbaidjan are compared with the mean data in the country. Oil industry workers of mainland and shelf turned out to have different levels of occupational morbidity, depending also on the age and length of service. PMID- 1308872 TI - [Principles and methods of evaluating tension of the functional systems in the body during work]. AB - Grounded and worded concept stresses that the intensity of regulating mechanisms must be taken into account in evaluating the difficulty and intensity of work, criteria of intensity are suggested. Growth of intensity index, centralized administration or considerable number of correlations (above the average on the whole industry) and more synchronized functions during the work improve the intensity of work by one step above the results of the simple physiological evaluation of work intensity. PMID- 1308873 TI - The cementless PCA primary total hip system. Medium-term follow-up of 235 cases. AB - The Porous Coated total hip Arthroplasty (PCA), used by the authors since August 1984, represents a considerable advancement in the field of prosthetic replacement. Its original design and biological fixation give it long-lasting stability not only in young patients, but also patients with initial osteoporosis. Its use in cases of advanced osteoporosis, however, is more controversial. The 8-year results are quite satisfactory from both a clinical and radiographic standpoint, confirming, as other authors have reported, that the medium and long-term results of cementless total hip replacement tend to stabilize because there is a lack of late reactions, which are more common in cemented implants. PMID- 1308874 TI - Correction of lower limb deformity using external fixation. AB - The authors report their experience in treating angular and rotational deformities of the lower limb by an original method consisting of corticotomy and gradual distraction with an external fixator on the opposite side of the limb as the deformity. The Castaman angular and Monticelli-Spinelli circular external fixators were employed (Castaman, 1983; Monticelli and Spinelli, 1983, 1986, 1987). PMID- 1308876 TI - Ultrastructural analysis of the adaptation of articular cartilage to mechanical stimulation. AB - Ultrastructural analysis was conducted on samples of articular cartilage taken from both load-bearing and non-load-bearing areas with the aim of evaluating the morphologic adaptation of the articular cartilage to mechanical stimulation and identifying the mechanisms of interaction of the chondrocyte and the matrix. Through this analysis we were able to better define the adaptation process of the cartilage as well as the modalities of mechanical stress transmission. We believe that the complex formed by the chondrocyte, the pericellular matrix, and the pericellular capsule constitutes the biomechanical unit of the articular cartilage which serves as the sensor and transducer of mechanical stress. The arrangement of the collagen fibers and the proteoglycans which make up the pericellular capsule and membrane around the chondrocyte can be compared, from a mechanical standpoint, to a dynamic structure constructed in order to absorb the load stresses and protect the internal environment. From a biological standpoint, these are comparable to an extracellular-scaffold constructed with the aim of mediating the interaction between the chondrocyte and the territorial and inter territorial compartments. PMID- 1308875 TI - CT arthrography and arthroscopy in chronic glenohumeral joint instability. AB - The authors evaluate the value of CT arthrography in glenohumeral joint instability. A study was conducted on a group of 16 patients with recurrent dislocation of the shoulder. All patients underwent CT arthrography and arthroscopy. The diagnostic accuracy of CT arthrography was rated for different types of lesions on the basis of arthroscopic confirmation of its findings. Our results, which include a statistical analysis, showed a diagnostic accuracy of 97.3% in Bankart lesions and 100% in Hill-Sachs lesions and loose bodies. Dilation of the subscapular bursa and injury of the glenoid labrum-IGHL complex were often identified, while chondritis and synovitis were less frequently diagnosed. The authors therefore conclude that CT arthrography may be considered an extremely reliable diagnostic test for obtaining an overall picture of injuries due to instability. Arthroscopy, on the other hand, should be reserved for cases in which surgery may be performed in the same stage as diagnosis. PMID- 1308877 TI - Radial head fracture treated by resection. Long-term results. AB - Thirty-one patients who underwent resection of the radial head for fracture of the radial head were reviewed after an average of 17 years. These patients were divided into three groups according to the type of fracture and treatment: group 1 had undergone complete resection due to isolated radial head fracture, group 2 partial resection due to isolated fracture, and group 3 complete resection due to radial head fracture associated with other lesions in the same arm. The clinical results were satisfactory in 72% of the group 1 patients, none of the group 2 patients, and 60% of the group 3 patients. In 55% of the patients an increase in the valgus angulation of the elbow was observed, modest in most instances. In almost half of the patients, all of which had full range of elbow motion, a new radial head had formed. Eighty percent of the patients had clinically asymptomatic distal subluxation of the radioulnar joint. In most cases of isolated radial head fracture, complete resection yields satisfactory long-term results. Partial resection, on the other hand, has a high incidence of failure. The presence of other osteoarticular lesions in the same arm significantly reduces the chances of success. PMID- 1308878 TI - Emission spectrophotometric analysis of titanium, aluminum, and vanadium levels in the blood, urine, and hair of patients with total hip arthroplasties. AB - Emission spectrophotometry was used to measure the levels of titanium, aluminum, and vanadium in the blood, urine, and hair of 30 patients with total hip arthroplasties. The patients were divided into three groups of ten; one group was studied two years after total hip replacement, one at four years, and one at six years. High levels of titanium and aluminum were found in the hair, especially in the group studied six years after implantation, while the levels of the three ions in the blood and urine were not significant. PMID- 1308879 TI - The Elmslie-Trillat procedure for recurrent subluxation of the patella. One to five year follow-up. AB - Thirty-four patients who had undergone the Elmslie-Trillat procedure from 1985 to 1989 were examined in order to evaluate the effectiveness of this operation in the treatment of recurrent subluxation of the patella. The result of an increased Q angle accompanied by patella alta, femoral sulcus dysplasia, or vastus medialus obliquus dysplasia was also studied. Only those patients with recurrent subluxation of the patella took part in this study; cases of habitual or permanent dislocation, potential instability, traumatic dislocation, and degenerative arthritis were excluded. The patients were reviewed both clinically and radiographically, and the A.R.P.E.G.E. scoring system was used to evaluate the results. The follow-up period ranged from 1 year to 5 years and 4 months, with an average of 3 years. The overall results were excellent or good in 77% of the cases, as was the subjective knee stability rating in 87% of the cases and the pain rating in 82% of the cases. Recurrence of the subluxation was observed in only one instance. The results were not significantly different when the groups of patients with patella alta and type 1 femoral sulcus dysplasia were considered separately. The results were also excellent in the patients who underwent the Elmslie-Trillat procedure with reconstruction of the vastus medialis obliquus. In conclusion, surgical realignment of the anterior tibial tubercle confirmed its reliability in the treatment of recurrent subluxation of the patella. In cases of patella alta, the authors recommend lowering the anterior tibial tubercle only when the Insall-Burstein index is greater than 1.3. Femoral sulcus-plasty should be performed in cases of type 3 sulcus dysplasia. PMID- 1308880 TI - Atraumatic patellofemoral joint disorders. Long-term results of surgery. AB - Clinical and radiographic follow-up was done on a group of patients with atraumatic patellofemoral joint disorders who had been treated surgically by realignment of the extensor apparatus at the authors' institution from 1985 to 1989. The preoperative radiographic examination in the 65 patients treated (for a total of 74 realignments) evaluated the following parameters: sulcus angle, Insall-Salvati index, and congruence angle. The 46 patients who returned for follow-up (after an average of 2 years and 3 months) were evaluated clinically according to a classification system proposed by the authors which is based on objective clinical data and a multi-factorial assessment of pain. Moreover, radiographic follow-up of the same 46 patients made it possible to quantify the degree of realignment achieved with each type of surgical technique. The clinical and radiographic data made it possible to determine more precise indications for each type of surgical procedure in relation to the disease involved, using a correct diagnostic approach and making a thorough evaluation of the clinical, anatomical and pathological features. PMID- 1308881 TI - Torsional tibia vara. AB - Infantile tibial torsion and tibia vara are common childhood deformities with controversial methods of measurement and treatment. The authors believe that the two deformities are different manifestations of the same entity for which the term "torsional tibia vara" is adopted. A practical method of measurement and a decisive method of conservative treatment are presented for this disorder. The concept as well as the methods of measurement and treatment have been successfully practiced by the senior author (H.Z.) for the past 20 years. PMID- 1308882 TI - Clinical and radiographic evaluation of the Codivilla method of surgical correction of congenital club foot. Medium-term follow-up of 235 cases. AB - The authors review 30 patients with congenital club foot (CCF) who were treated surgically by a slightly modified Codivilla technique. Clinical morphologic, and functional follow-up was performed an average of 10 years later, and the findings were compared to the radiographic features. The final outcome was rated good in 41% of the cases, fair in 29%, and unsatisfactory in 30%. The authors found a close correlation between the grade of the initial deformity and the final outcome. Some sign of the deformity always remained, even when the functional outcome was excellent. PMID- 1308884 TI - Fracture of the polyethylene acetabular cup in total hip arthroplasty. PMID- 1308883 TI - The effect of chemotherapy on osteosarcoma. AB - The aim of this study was to evaluate the effect of chemotherapy on osteosarcoma by comparing the histologic pattern of primary tumors with that of their metastases. Therefore the primary tumors and metastases in 11 patients were macroscopically and histologically classified according to the Enneking and Broder systems as well as our own method. Three of 11 patients developed metastases with a less malignant pattern, 8 patients developed metastases which were as malignant as the primary tumor. The chemotherapeutics used had either an insubstantial effect or none at all on the differentiation of immature tumorous structures in the metastases and treatment did not lead to the expected improvement. Only the patients in whom, according to our own system, the primary tumors were classified as less malignant, are still alive. PMID- 1308885 TI - A fourth type of brachial plexus injury: middle lesion (C7). AB - The authors describe a fourth type of traumatic brachial plexus lesion which was found in 11% of injuries to the spinal nerve roots, trunks and cords. This lesion consists of isolated or predominant lesion of the middle elements. While high lesions are caused by shoulder trauma in a downward direction and low lesions by trauma in abduction, middle lesions are produced by trauma in an anteroposterior direction. The high incidence of this type of lesion led the authors to propose the following new classification: high lesions (C5, C6)(Duchenne-Erb); middle lesions (C7); low lesions (C8, T1) (Dejerine-Klumpke); complete lesions. PMID- 1308886 TI - Influence of an in-patient exercise program on scoliotic curve. AB - In 107 patients with idiopathic scoliosis radiographs were performed under standard conditions immediately before and immediately after a 4-6 week in patient exercise program at the Katharina-Schroth Hospital. The average angle of curvature as measured by the Cobb technique was 43.06 degrees (standard deviation = 22.87) before treatment and 38.96 degrees (SD = 23.00) after treatment. An improvement in the curve of 5 degrees or more was found in 43.93% of the patients, 53.27% were unchanged and in 2.8% the curve increased by 5 degrees or more. Altogether the improvements in curvature were highly significant. These results show that even in severe scoliosis the magnitude of the curve can be reduced by a specific rehabilitation program of physiotherapy. PMID- 1308887 TI - Allergy to components of total hip arthroplasty before and after surgery. AB - Sensitivity to a series of haptens was studied in two groups of patients by means of patch tests. The first group was made up of 66 patients with total hip replacements, 12 of whom had aseptic loosening of the implant. The second group, which was used as a control, consisted of 41 patients scheduled to undergo total hip replacement. Ten patients (15.1%) in the first group tested positive; one of these had aseptic loosening. In the control group, two patients (4.8%) tested positive. The theory that an allergy may be the cause of loosening has a biologic foundation, but it can only be used to explain a few cases. However, since considerable vanadium sensitivity was found, we suggest that this material be used as little as possible in the manufacturing of prosthetic components. PMID- 1308888 TI - Severely displaced fracture of the thoracic spine without neurologic lesion. A case report. AB - The author reports a case of severely displaced fracture of the thoracic spine without neurologic damage in a 27-year-old man. The lesion was treated by open reduction, internal fixation, and posterolateral spinal fusion. A precise description of the clinical, radiographic, and CT features of the lesion is provided in order to facilitate proper classification and treatment. PMID- 1308889 TI - Entrapment of the flexor digitorum profundus of the ring finger at the site of an ulnar fracture. A case report. AB - Entrapment of the ring finger flexor digitorum in the ulna following fracture of both forearm bones is very rare. Only three cases have been reported previously (Jeffrey, 1976; Rayan and Hayes, 1986). We report another case of such entrapment in an 8-year-old boy. PMID- 1308890 TI - Intratendinous ganglion and carpometacarpal boss. A report of two cases. AB - Two cases of intratendinous ganglion which developed over the underlying carpometacarpal boss, the dorsal osteoarthritic spur at the second or third carpometacarpal joint, are presented. The intratendinous ganglion, which may predispose the affected tendon to spontaneous rupture, must be differentiated from carpometacarpal ganglion and bursitis, which are usually asymptomatic. When the intratendinous ganglion associated with underlying carpometacarpal boss is removed, this bony prominence at the carpometacarpal joint which is the cause of irritation leading to mucoid degeneration and ganglion formation should also be excised. PMID- 1308891 TI - Research with a real purpose. PMID- 1308892 TI - The hole in the net. PMID- 1308893 TI - Sensei. PMID- 1308894 TI - Parallels between AIDS, leprosy and syphilis. PMID- 1308895 TI - Gestational diabetes in a rural setting. AB - Women who are already diabetic and become pregnant, as well as women who develop gestational diabetes, have increased risks of complications to both fetus and mother. These risks in gestational diabetes mellitus (GDM) can be reduced to near that of a non-diabetic mother by normalizing the blood sugar. The current recommended standards are reviewed. Utilizing a team approach, care was provided to patients with GDM in a rural primary care setting in order to attempt to normalize the blood sugar to the recommended level. Review of the outcomes of these pregnancies supports the conclusion that acceptable care for patients with GDM can be provided away from the tertiary care centers and in the primary care setting. PMID- 1308896 TI - [Evaluation of 1st semester activity of the Algiers Poison Center]. AB - The Poisons Center located in Bab el Oued University Hospital of Algiers has been opened to the public since January 2, 1991. The staff is made of public health physicians and pharmacists residents trained in toxicology. Phone calls are a new means for obtaining advice on poisonings and the public must be informed on the modalities of use. The number of calls shows that people are willing to use this fast and effective medium. A specific data sheet was created. The analysis of calls includes the origin of call, the nature of products used, the age range the clinical condition of patients, the recommended treatment and the outcome when known. PMID- 1308897 TI - [Acute amoxapine poisoning with rhabdomyolysis and acute renal insufficiency]. AB - Acute renal failure and rhabdomyolysis are reported in a 33 year old man who had taken 6 g of amoxapine. Different possible levels for the toxic action of amoxapine are discussed and compared with literature data. PMID- 1308898 TI - [A chemical necrosis]. PMID- 1308899 TI - [Rapid characterization of stupefacient and toxic substances by pressurized thin layer chromatography]. PMID- 1308900 TI - [Comparative urinary elimination of caffeine in sedentary and sportsmen after administration of Guronsan]. AB - The authors present the results of a study on urinary excretion of caffeine, after a single oral intake of 100 mg of caffeine, in two populations of students at rest and during exercise. Whether expressed in mg/l or mg/g creatinine no significant difference in urinary excretion of caffeine was observed between the two populations and it proves to be lower than the limit level authorized by the IOC (12 mg/l). PMID- 1308901 TI - Relationship between enterotoxigenic Escherichia coli and diarrhea among children in Buenos Aires. AB - The incidence of enterotoxigenic Escherichia coli (ETEC) has been studied in 85 children with acute diarrhea in patients in the Hospital de Ninos Pedro de Elizalde, Buenos Aires, and in 38 healthy children. All of them were up to four years old and none had received antibiotic treatment within 7 days before sampling. ETEC was recovered in 9 out of 85 (10.6%) children with diarrhea. From these positive cases, 6 were associated with heat-stable (ST), 1 with heat-labile (LT) and 2 with both LT and ST enterotoxins. Only one case (2.6%) of LT-producing ETEC was detected in the control group. In 5 out of 9 ETEC diarrhea cases (55.5%) the isolated strains expressed human colonization factor antigens (CFA); four of them were CFA/I and one CFA/II. The characteristics of the CFA, biotype, serotype and antibiotic sensitivity pattern were studied in 23 E. coli isolates from 10 ETEC positive children. Of the 12 ST only strains, 5 (41.7%) expressed CFA/I and 2 (16.7%) CFA/II (CS2 + CS3). One out of 2 LT/ST strains expressed CFA/I. CFAs were not detected in the ETEC-LT nor in the toxin negative E. coli strains. From the ETEC isolated, 82.4% were resistant to 4 or more antibiotics, whereas only 50% of simultaneously isolated toxin-negative E. coli presented this sensitivity pattern. The different ETEC strains belonged to several different serotypes, some of them rarely observed in other countries. None of these serotypes correlated either with the toxin profile or with the sugar fermentation pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308902 TI - [Clinical and biochemical study of 9 patients with hereditary elliptocytosis]. AB - Using clinical, functional and biochemical criteria, we studied the red blood cell membrane of nine caucasic patients from four families with hereditary elliptocytosis (HE). From a clinical point of view, seven cases were classified as compensated mild HE in whom anemia and splenomegaly are absent and reticulocytosis is slightly elevated or normal. Two cases were uncompensated mild HE with anemia, reticulocytosis, splenomegaly and erythrocytic fragmentation. (Table 1). Three individuals from one family displayed a significant reduction of protein 4.1 by polyacrylamide gel electrophoresis; one of them was uncompensated HE. The patterns of limited tryptic digestion and dimer/tetramer proportion of spectrin were normal. The study of red cell deformability by ectacytometry revealed that the cell deformability under isotonic conditions was decreased in all HE patients and the curve obtained had trapezoidal shape (Fig. 3). We found that the deformability index correlated well with the degree of anemia, but no correlation was observed between clinical findings, morphological phenotype and specific molecular etiology. According to our knowledge, this is the first report on molecular and functional studies in HE in Argentina. PMID- 1308903 TI - [Definition of hypertension based on a prevalence study of 1,423 young adults]. AB - The prevalence of arterial hypertension (AH) was studied in 1423 individuals (702 males and 721 females) aged 21 years (Fig. 1, Table 1). Systolic (SBP) and diastolic (DBP) blood pressures and heart rate (HR) were measured three times on two different occasions separated by at least one week. Three different criteria were used to define AH (Table 3): 1) World Health Organization (WHO) [PAD > or = 95 mmHg in one casual determination]; Joint National Committee IV (JNC-4) [PAD > or = 90 mmHg on two different occasions]; and 3) Statistical [PAD > percentile 95 of the respective distribution]. BP was distributed normally in both males and females (Fig. 4). DBP decreased progressively along the six measurements (Fig. 2, Table 2), with the average of DBP determinations 4-6 being significantly lower than the average of determinations 1-3 (p < 0.05). SBP behaved in the same way (Fig. 2, Table 2), but in this case the 2nd and 3rd determinations within each occasion (2-3 and 5-6) were significantly lower than determinations 1 and 4, respectively (p < 0.05). As a result, the percentage of individuals of either sex with DBP > 90 mmHg was 14.7% based on the 1st determination (Fig. 5), but if the averages of determinations 1 to 3 or 1 to 6 were considered, these percentages decreased to 8.7% and 4% respectively (Fig. 5). With the WHO criterion (PAD > or = 160/95 mmHg based on the first determination) there were 3.3% of individuals with AH. With the statistical criterion the prevalence of AH was always 5%, but the actual value of percentile 95 was progressively lower as we took into account the 1st. determination, the average of 1-3 or the average of 1-6: 100, 95 and 90 mmHg in males and 90, 88 and 84 mmHg in females, respectively (Fig. 6). With the JNC-4 criterion there were 1.6% of individuals with AH (Fig. 5). These low figures were caused by the lack of repeatability of DBP readings in the second determination, since 79% of the individuals with DBP > or = 90 mmHg on the first occasion were normotensive on the second one, whereas more than 95% of those being initially normotensive remained in that category on the second visit (Fig. 7). The FC did not show important changes (Fig. 8), and the percentage of individuals with systolic AH was low (Table 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308904 TI - [Phenotypic expression variation of isovaleric acidemia in Argentinian patients. A long term follow-up]. AB - In this paper we discuss the first five Argentinean patients presenting isovaleric acidemia (IVA), an alteration of leucine catabolism due to a genetic defect of isovaleryl-CoA dehydrogenase. Belonging to unrelated families, one from native (H. Fam.) and the other from Italian ancestry (M. Fam.); the patients presented the clinical pattern highly suggestive of the disease: they were siblings, had disease-free intervals, vomiting, ketoacidosis crises, "sweaty feet" odor and progression of the neurologic involvement from somnolence and stupor to profound coma. In the four children of H. Fam. the disease had a late but severe beginning; one of the girls died (N.H.). The boy from M. Fam. presented a neonatal form of clearly benign course. The disease was confirmed by gas-chromatography (GC) of volatile acids in serum and also by the typical urinary acid GC-profiles (Fig. 1, A and B); the isovalerylglycine quantitative evaluation in urinary samples collected during crises is shown in Table 1. The morphological findings in liver and brain of N.H. showed at the ultrastructural study, an extensive fatty degeneration and greatly marked mitochondrial alterations in the liver and edema, neuronal karyorrhexis and karyolysis in the brain (Fig. 2). The therapeutic protocol based on a low leucine or low protein diet and use of glycine is described. The evolutionary follow up, more than 10 years for the first case, showed a normal mental development in three of them and retardation in the first child of H. Fam., who had a late diagnosis. IVA is still valuable as a paradigm in the acquisition of a highly clinical suspicion and for its introduction in the study of genetic organic acidemias. PMID- 1308905 TI - [Neuropsychologic evaluation in Parkinson disease]. AB - For decades Parkinson's disease has been considered to be limited to disturbed motor functions and its association with a cognitive deterioration is very recent. The frequency of cognitive decline varies according to the authors between 3% and 93% depending on the different criteria of evaluation. Owing to the discrepancy among the previous studies our object has been to determine the existence of cognitive changes of statistical significance, since even nowadays the relation between neuropsychology and physiopathology has been misunderstood. A total of 50 patients between 52 and 85 years old with Parkinson's disease have been neurological and neuropsychologically evaluated and the results correlated with 50 healthy controls. Patients, who presented clinical signs of demence according to the criteria of DSM III or any other neurological or general disease were excluded because of possible side effects on the motor cognitive phase. For the neuropsychological study Signoret's Battery of Cognitive Efficiency test (BEC 96) was used, it evaluates: the attention, orientation, thinking, memory, recognition, serial learning, fluency, naming and constructional functions. It was observed that all the patients with Parkinson's disease performed these tests worse than the controls, except for attention. From the statistical point of view the differences are highly significant (p < 0.001) for serial learning and constructional tests and significant (p < 0.05) for orientation, thinking fluency and naming. In the area of mnesic functions the patients with Parkinson's disease show an alteration that predominates significantly on serial learning, however, it is less important for logical memory. All the alterations correspond to the long term memory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308906 TI - [Prevalence of high normal blood pressure and progression to hypertension in a population sample of La Plata]. AB - In 1985 we investigated the prevalence of high normal blood pressure in 6387 inhabitants (range 15-75 years old) of the city of La Plata and its progression to arterial hypertension after four years. High normal blood pressure was defined as a systolic blood pressure (BP) < 140 mmHg and diastolic BP between 85-89 mmHg (average value of two measurements) on one occasion. Arterial hypertension was defined as a systolic BP > or = 140 mmHg and/or diastolic BP > or = 90 mmHg, both as an average of two measurements on two occasions. High normal BP prevalence was 6.62%, being higher in men than in women (p < 0.0005, Table 1). General progression to hypertension was 41.79%, being higher in the older individuals (p < 0.0005). Of the 423 individuals with high normal BP (Table 2), 268 (63.36%) were found in 1989 (Table 3). They had an incidence of hypertension of 10.45% per year, also higher in older subjects (Table 4). There were no differences between sexes. Subjects with high normal BP who subsequently developed hypertension had higher systolic BP in 1985 than those who remained normotensive (p < 0.001, Table 5). Most of them progressed to mild diastolic hypertension (29.48%) or borderline isolated systolic hypertension (6.72%, Fig. 1). In this study, progression to arterial hypertension was higher than that reported in similar studies for general population in other countries. PMID- 1308907 TI - Effect of glucose infusion in dogs on blood sugar, insulinemia and serum free fatty acid responses. AB - A glucose dose-response study, in normal dogs, was performed in vivo. Glucose doses: a) priming 700 mg/kg body wt, i.v.; b) intravenous infusions: 20 (Group I), 28 (Group II), 44 (Group III) and 100 mg/kg body wt/min (Group IV) for 60 min. The following responses were studied: blood sugar, serum immunoreactive insulin and serum free fatty acids. There were significant effects of the dose of infused glucose on blood sugar and serum insulin integrated responses; the integrated serum free fatty acid response was not influenced. Mean integrated blood sugar responses in groups I, II and III coincided, while that observed in Group IV was increased. Mean integrated serum insulin response in group III was above those found in I, II and IV; the response in II was below the one detected in IV. In groups I and II, there was a linear inverse relationship of blood sugar to serum insulin integrated responses; this relationship vanished as data from groups III and IV were also included in the calculation of respective product moment correlation coefficient. There was a significant effect of the dose of infused glucose on the insulinogenic index during glucose test. Mean insulinogenic indices in groups II and IV were below that of group III. A small unique peak of insulin response in group I during glucose infusion test was observed. A typical biphasic insulin response in systemic venous blood of animals of group II, was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308909 TI - [Recurrent infections, medullary dysfunction, and kidney disease]. PMID- 1308908 TI - [Massive proteinuria and HELLP syndrome]. AB - HELLP syndrome continues to be a clinical entity of difficult diagnosis. Weinstein first defined it in 1982 giving the practicing obstetrician a sequence of useful initials (H = hemolysis; EL = elevated liver enzymes; LP = low platelets). Since then a lot has been written and it has become clear that the syndrome is a form of severe preeclampsia. The American College of Obstetrics and Gynecology does not include HELLP in the description of severe pre-eclampsia as such but does accept each of its components as being part of severe pre eclampsia. The case presented deals with a 33 year old white female, admitted at 27 weeks gestation with nausea, epigastric pain resembling acute abdomen, nose bleeding and mild hypertension. The analysis revealed an abnormal liver profile with elevated GOT, GPT and LDH, heavy proteinuria (14.4 g/day), decreased platelet count (92000/mm3) and elevated total bilirubin. Pregnancy was terminated by cesarean section 24 hours after admission because the patient's condition was deteriorating. Obviously in pre-eclampsia/eclampsia there is a systematic injury to all tissues. Proof of this is the hypertension as a consequence of vascular spasm and proteinuria due to glomerular injury. In HELLP the sequence of events is probably altered; hepatic injury precedes vascular and renal injury of conventional preeclampsia. The syndrome results from many clinical and pathological symptoms derived from endothelial microvascular injury which determine a rapid platelet activation causing vascular spasm, platelet aggregation and further endothelial injury through a feedback mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308910 TI - [Sleep apnea syndrome]. PMID- 1308912 TI - [Stress and hypertension]. PMID- 1308911 TI - [The new techniques for ventilatory assistance]. PMID- 1308913 TI - [From physicians to medicine dealers]. PMID- 1308914 TI - [Bone mineral content and treatment with deferoxamine in patients under chronic hemodialysis]. PMID- 1308915 TI - [HTLV-1 infection in polytransfused patients]. PMID- 1308916 TI - [Rapid correction of acute hyperkalemia with nebulized salbutamol]. AB - Fifteen patients on chronic hemodialysis received twenty-two treatments with 20 mg nebulized salbutamol (4 ml of 0.6 g% in 4 ml of saline), to control an episode of acute hyperkalemia, (6.58 +/- 0.14 range: 5.7-7.9 mEq/l) and as a previous step before dialysis. Plasma potassium concentration at 20, 40, 60, 90 and 180 min post-salbutamol, were: 5.85 +/- 0.21, 5.58 +/- 0.21, 5.48 +/- 0.27, 5.46 +/- 0.17 and 5.57 +/- 0.34 mEq/l, respectively. (Fig. 1). The decrease of plasma potassium was significant at 40' and maximal at 90': 1.12 +/- 0.10 mEq/l, and persisted for at least 3 hours (in 3 patients up to 6 hours). No correlation was found between the grade of hyperkalemia and the magnitude of plasma potassium decrease after therapy. The systolic and diastolic blood pressure decreased significantly at 60 and 80 min post-treatment: 134 +/- 6.45 vs 119 +/- 6.79 and 74 +/- 4.12 vs 64.66 +/- 3.88 mmHg (p < 0.02 and p < 0.001). The heart rate and respiratory frequency increased significantly at 60-80 and 20 min respectively (90 +/- 4.45 vs 113 +/- 4.55 beats/min and 19.57 +/- 0.98 vs 23.42 +/- 1.24 resp/min) (p < 0.001) (Table 1). The secondary effects of the administration of the drug, such as sinus tachycardia, fine tremor and anxiety in 6, 4 and 1 patient respectively, were moderate and well tolerated. It is concluded that, due to its technical feasibility, promptness of action, duration of hypokalemic effect, few side effects and repeatability, nebulized salbutamol can be considered a first choice in the treatment of acute hyperkalemia. PMID- 1308918 TI - [Gamma-ray bone densitometry and evaluation of the patient at risk for osteoporosis]. AB - After having briefly illustrated the main theories of photonic ray bone densitometry, the authors describe the various techniques used to evaluate bone mass and bone mineral density as accurately and precisely as possible both at an appendicular level and at lumbar and femoral sites. Since these data only provide a static measurement and are unable to provide information regarding bone mass evolution in time, a method is illustrated which is theoretically capable of identifying high risk subjects, namely those who, on the basis of simple blood and urine tests for some biochemical parameters, are likely to undergo a significant reduction in bone mass in the future. Lastly, the paper reports the preliminary results of a study carried out in immediately post-menopausal women in whom rapid loss of bone mass was followed by a greater reduction in bone mineral density measured at an appendicular level. PMID- 1308917 TI - [The diagnosis of metabolic bone diseases]. AB - Physical semeiotics, the laboratory, radiology and histology represent the diagnostic tools for metabolic bone diseases. Past medical history and a full objective examination form the basis for every type of diagnostic and therapeutic approach. Familial patterns, the range of drugs used by the patient, the concomitance of diseases affecting mineral metabolism, and the presence of deformities or typical characteristics of some clinical conditions allow the clinician to orientate his diagnosis. Some laboratory tests (serum calcium and phosphate, calciuria) are useful for screening, whereas others (parathyroid hormone and other calciotrophic hormones, biochemical parameters of bone remodeling) must be carried out only for precise diagnostic purposes. In addition to highlighting and characterizing fractures, plane radiology is indicated for the differential diagnosis of focal bone diseases. In the latter diagnosis is facilitated by bone scintigraphy which reveals areas of accelerated bone remodelling. The quantitative evaluation of bone mass using non-invasive methods is of fundamental importance in osteopenic syndromes. Of all the techniques evolved in the past, only quantitative computerized tomography and X-ray computerized mineralometry are used today in the diagnosis and management of osteoporotic patients. The choice of one or other technique should be based on the clinical necessity and on their respective accuracy and reproducibility. Histomorphometric bone biopsy is indicated only in cases of rapid bone loss with uncertain biochemical conditions and for the diagnosis of mineralization disorders. PMID- 1308919 TI - [Quantitative computerized tomography in the study of osteoporosis. Our experience]. AB - In the diagnosis of osteoporosis there are, today, several techniques for investigating bone mineral density. In this work the authors evaluate the sensitivity of Computed Tomography in the diagnosis of this metabolic disease, because of the built-in competence of this method in determining the density of the anatomical tissues. In a randomised study the Authors performed Single Energy Quantitative Computed Tomography (SEQCT) in estimating the bone mineral density of lumbar vertebrae in 44 female patients. The data obtained were correlated, using the Student "t" test, to the measurements acquired, in the same group of patients, employing Dual Energy X-ray Absorptiometry (DEXA), 27 patients, and Total Body DEXA, 17 patients. Results revealed a good correlation between SEQCT and DEXA (R = 0.89) and statistical significance (p < 0.001). On the contrary there is not a good correlation (R = 0.58) if SEQCT is compared to Total Body DEXA. According to our experience Quantitative Computed Tomography is useful in diagnosis osteoporosis and it should be performed in all post-menopausal patients. This method, which has a high level of precision, is cheap and easily adaptable to every Computed Tomography. Because of the high X-ray dose rate, only DEXA should be performed in monitoring patients undergoing therapy. PMID- 1308920 TI - [Ultrasonography techniques in the evaluation of the osteoporotic patient]. AB - Previous studies have shown a significant but weak correlation between speed of sound (SOS) and broadband ultrasound attenuation (BUA) in bone, and densitometric bone measurements. These findings indicate that these techniques reflect different properties of bone. We measured SOS and BUA in the os calcis (Achilles, Lunar Corp.) and bone mineral density of the lumbar spine (BMS-LS; by DEXA) and of the ultradistal radius (BMD-UDR; by DPA) in 60 postmenopausal women (age range 50-65): 30 were osteoporotic women (OP) and 30 were age-matched normal postmenopausal women (N). Mean values of SOS and BUA resulted significantly lower in OP group (p < 0.001). SOS and BUA measurements significantly correlated with DEXA of the lumbar spine (r = 0.52 p < 0.001, r = 0.56 p < 0.001, respectively) and DPA of ultradistal radius (r = 0.60 p < 0.001 and r = 0.62 p < 0.001, respectively). In conclusion, these techniques show good correlations with absorptiometric techniques. The best correlation has been found between BUA and DPA of ultradistal radius. Furthermore, US techniques are able to separate a normal from an osteoporotic population. Therefore, US techniques seem to be a useful tool for screening of osteoporotic disease. PMID- 1308922 TI - [Effect of cyclosporin A, azathioprine, and methylprednisolone on plasma levels and heart atrial content of atrial natriuretic peptide in the rat]. AB - In Wistar normotense male rats of six months old the effect of Cyclosporine A (Cys A), azathioprine (AZA) and methyl prednisolone (M-Pred), alone or associated, on the plasmatic levels and atrial content of the atrial natriuretic peptide (PNA) have been studied. The values of creatinine, urea, sodium a potassium were also measured in serum. This treatment was maintained for 30 consecutive days at these doses: Cys A (5.00 mg/kg b.w./day), AZA (2.50 mg/kg b.w/day) and M-Pred (20.00 mg/kg b.w./day), being the peritoneal the way of administration. Eight groups were organized: control, vehicle, Cys A, AZA, M Pred, Cys A + M-Pred, AZA + M-Pred, Cys A + AZA + M-Pred. All the above parameters were estimated at 24 hours after respective injections. No changes are found after Cys A or AZA in the plasmatic and atria contents of PNA. Nevertheless, m-Pred alone or in association determines high increases of PNA in plasma and tissue. The other parameters are unchanged. The data reveal the beneficial use of M-Pred, glucocorticoid of the low mineral activity, in the therapy of rejection in cardiac transplantation. On the other hand, Cys A and AZA appear not to be important in the secretion and atrial synthesis of PNA. PMID- 1308921 TI - [Methodological basis and clinical applications of total-body densitometry]. AB - With the advent of dual-energy x-ray absorptiometry (DXA) total body scans can be done in only 10-20 minutes rather than the 60-80 minutes required by dual-photon absorptiometry (DPA). The DXA approach replace the Gd153 radionuclide source of DPA and provides substantially greater output intensity. The higher radiation flux achievable provides several advantages over conventional DPA: this makes total body scans routinely accessible. The measures of the entire skeleton and its major subregions cut down the problems of representativeness and relocation. The short term precision (coefficient of variation) was 0.5% for total body-bone mineral density (BMD) and about 1% for regional-BMD. We studied 885 women; study cohort consisted of 161 healthy postmenopausal women, 357 healthy postmenopausal women and 367 osteoporotic women with one or more vertebral crushes. The results indicate that bone mass begin decreasing during the last period of the premenopausal phase; the advent of menopause brings about a dramatic reduction of both total body and single area BMD: this phenomenon is particularly marked in subjects with osteoporosis. The single most important factor in determining BMD changes, is years since menopause. In order to assess the ability of DXA total body to distinguish women with postmenopausal osteoporosis of variable radiological degress from healthy postmenopausal women, we studied 330 postmenopausal females aged 42-85 years. There were 63 healthy women who were considered controls (Group 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1308923 TI - [Long-term treatment of central diabetes insipidus with oral DDAVP]. AB - Clinical use of the DDAVP (1-Deamino-8-D-Arginine Vasopressin) is now the first choice in treatment of Central Diabetes Insipidus. It is an analogue of Vasopressin with a higher antidiuretic potency, less vasopressor activity, and a longer duration of action. This drug still presents some problems of administration route. A lot of studies were published about different administration routes of DDAVP: sublingual tablets, parenteral solution, nose spray and suction de-epithelialized skin. Some authors have utilized the oral route (solution or tablets) with good results in short-term treatment. We think the formulation in tablets of DDAVP is an efficacious support of the therapy in this disease also for long-treatment. In our study 3 patients with Central Diabetes Insipidus (aged 22-56; 2 idiopathic and 1 post-surgery) previously treated with DDAVP nasal solution (10 micrograms/day; 36-156 months), have been submitted to a chronic treatment with DDAVP tablets for a period of 24-36 months. The DDAVP tables were administered at the dosage of 400-600 micrograms/day in 2-3 administrations. The patients were studied at intervals of 3-6 months, and on each occasion full blood count, glucose, azotaemia, creatinine, liver function tests, electrolytes, urine volume, density and osmolality were estimated. The long-treatment with oral DDAVP was able to keep a good control of the disease in all patients. In case 1 we had a significant reduction of urine volume (p < 0.01) and a significant increase (p < 0.01) of urine osmolality in comparison with previous treatment with nasal solution; in case 2 and 3 no significant changes were observed. No side effects were noted during this study. The drug has been well tolerated and the compliance of patients was better during oral DDAVP than nasal solution. In our opinion the oral DDAVP is an effective and safe solution for the treatment of Central Diabetes Insipidus, and give to the patients a better quality of life in comparison to the nasal solution. PMID- 1308924 TI - Chemotherapy and the immune system. PMID- 1308925 TI - Preface: positive interactions between anti-infection drugs and the immune response: an emerging paradigm. PMID- 1308926 TI - Hypothesis: impaired immunity as a factor which contributes to the spread of drug resistance. AB - Evidence has accrued to indicate that host defence mechanisms enhance the efficacy of many of the drugs used to treat infectious diseases. Because of this, and also because of the likelihood of increased pathogen loads in immunoincompetent hosts, some infections are less likely to be completely cured by normal regimens of chemotherapy in individuals with drastically impaired immune responsiveness. In such circumstances natural selection could result in the accelerated emergence of drug-resistance pathogens. PMID- 1308927 TI - Cyclosporin A: antiparasite drug, modulator of the host-parasite relationship and immunosuppressant. AB - Cyclosporin A (CsA), a cyclic undecapeptide with powerful properties of immunosuppression, acts on parasitic infections in laboratory animals in various ways. The outcome of drug administration in vivo varies with timing of treatment relative to infection, route of administration, dose and number of treatments applied. CsA is clearly antiparasitic against malaria, schistosomes, adult tapeworms, metacestodes and filarial nematodes. By contrast, it acts as an immunomodulator against trypanosomes and Giardia, by exacerbating infection; in the case of Leishmania spp. the drug acts variously. In some other infections CsA acts both as an antiparasite drug and as an immunosuppressant (Toxoplasma, avian coccidiosis and gastrointestinal nematodes). This range of activities is reviewed and possible modes of action discussed in the light of emerging data on in vitro drug activity and on putative receptor binding. The potential value of a non immunosuppressive analogue of CsA in the control of parasitic infections of humans and domestic animals is considered but this paper lays particular stress on the seminal role of CsA as a laboratory tool. PMID- 1308928 TI - Immune-dependent chemotherapy of schistosomiasis. AB - Host immune responses have been shown to enhance the efficacy of several schistosomicidal drugs. The evidence derives mainly from experiments on Schistosoma mansoni infections in the mouse with their immune status variously modulated; this review emphasises praziquantel (PZQ), which is now the main drug used for treatment of human schistosomiasis. Electron microscopy and indirect immunofluorescence indicate that PZQ disrupts the integrity of the surface membranes of S. mansoni, particularly those covering the dorsal tubercles of adult male worms, and this causes antigens which are the targets of antibody attack to be revealed. We review the evidence that two S. mansoni antigens in particular are implicated in the immune-dependent action of PZQ: a 200 kDa glycoprotein and a 27 kDa antigen with non-specific esterase activity. Consistent with the involvement of the latter antigen, increased non-specific esterase activity was demonstrated histochemically on the surface of intact PZQ-treated male worms, and we describe a chromogenic substrate assay for quantifying the amount of esterase activity that is exposed after drug treatment. The potential relevance of these observations for enhancing the efficacy of drugs currently used to treat human schistosomiasis, and for devising novel therapeutic strategies, is discussed. PMID- 1308929 TI - Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug. AB - Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals. It may also account for the inconsistencies in the effects of DEC against different filariae in different host species. In addition, we discuss the significant side-effects often associated with treatment of heavily infected patients, and the longer-term changes in T-cell reactivity and the host-parasite relationship which follow successful treatment with DEC. PMID- 1308930 TI - Immunomodulatory agents in the laboratory and clinic. AB - This paper reviews naturally occurring and synthetic compounds that either enhance immune defences or lower both natural and acquired immunity. Immunomodulatory agents used both for laboratory study and clinically for the management of immunologically based diseases are considered. PMID- 1308931 TI - Malaria: drug use and the immune response. PMID- 1308932 TI - Interactions between immunity and chemotherapy in the treatment of the trypanosomiases and leishmaniases. AB - The immune status of a host infected with Trypanosoma spp. or Leishmania spp. can play an important role in successful chemotherapy. In animal models, treatment of African trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. An intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. Similarly, an efficient cell-mediated immune responses is required for maximal efficacy of pentavalent antimonials in the treatment of leishmaniasis. However, the potential relationship between parasite-induced or acquired immunosuppression and effective chemotherapy has been poorly studied. Macrophages which have been activated by bacterial cell wall components or gamma-interferon are known to display increased activity against Leishmania donovani or Trypanosoma cruzi. In experimental and clinical visceral leishmaniasis, use of macrophage activators together with pentavalent antimonials has lowered the dose of antimony required to cure the infection. PMID- 1308933 TI - Interactions between chemotherapy and immunity in bovine theileriosis. AB - In bovine theileriosis the use of chemotherapy to control an infection sufficiently long to permit the establishment of a solid protective immune response has been developed as a routine vaccination procedure. Infections with Theileria parva and T. annulata can be prevented by the administration of carefully controlled numbers of sporozoites simultaneously with a long acting tetracycline and this form of immunization has been widely used for the control of East Coast fever in Africa with considerable success. In this review, the nature of the chemotherapy, the immune response and the interactions between chemotherapy and immunity in the development of infection-and-treatment immunization procedures are discussed. PMID- 1308934 TI - Chemotherapy and immunity in opportunistic parasitic infections in AIDS. AB - Parasitic diseases are endemic in parts of the tropics, but there is no convincing evidence that their prevalence or incidence is increasing due to the HIV epidemic. Available scientific data on parasitic infections in patients with the Acquired Immunodeficiency Syndrome (AIDS) suggests a predominance of Pneumocystis carinii, Toxoplasma gondii and Cryptosporidium spp. For reasons which are unclear, parasitic infections such as Plasmodium falciparum, Strongyloides stercoralis and Entamoeba histolytica, where cell-mediated immune responses are also thought to be significant, do not appear to be opportunists of importance. It is being increasingly recognized that chemotherapy for parasitic diseases has a host-dependent component, although scientific data on this subject remain scanty. The management of opportunistic parasitic infections in patients infected with HIV is dogged by failures and relapses, aptly illustrating the notion of the relationship between chemotherapy and the immune response. This review discusses the immunity and chemotherapy of opportunistic parasite infections in patients infected with the Human Immunodeficiency Virus (HIV). PMID- 1308935 TI - [The evolution of chronic chagasic cardiopathy. I. The influence of parasitemia]. AB - During eight years (1982-1990) the evolution of chronic chagasic cardiopathy and its relation to parasitemia was evaluated in 279 patients, 85 men and 194 women, studied by resting electrocardiography and xenodiagnosis. All patients were residents in Virgem da Lapa, State of Minas Gerais, Brazil and their ages varied from 7 to 76 years (average 42.6 y). According to the results of the electrocardiograms the evolution of chagasic cardiopathy was classified as a) unchanged--when there was no change of the initial pattern off the ECG, b) progressive--when there was deterioration of the ECG pattern and c) regressive when there was normalization or regression of the ECG alterations. Regarding xenodiagnosis 120 were considered with positive parasitemia, one or more xenodiagnoses positive, and 159 with negative parasitemia--all xenodiagnoses negative. The results showed: a) chagasic cardiopathy unchanged in 172 (61.6%) patients, b) progressive in 99 (35.5%) patients and c) regressive in 8 (2.9%). There was no relation between the evolution of chagasic cardiopathy and parasitemia. Independent from parasitemia, the cardiopathy was progressive according to the age of the patients and significantly greater in males. In conclusion we can state that evolution of chronic chagasic cardiopathy is associated with the age and with the male sex, but not with parasitemia, and this may suggest that parasitemia is not related to the development of the chronic chagasic cardiopathy. PMID- 1308936 TI - [The assessment of parasitemia in women who are carriers of Trypanosoma cruzi infection during and after pregnancy]. AB - This paper presents an evaluation of the parasitemic profiles of 119 women chronically infected with T. cruzi. Xenodiagnosis (xenos) were applied during (465 xenos) and after pregnancy (363 xenos) in order to detect possible variations in parasitemia in these periods. The frequency of positive xenos was greater during than after gestation. Otherwise, the frequency of infected triatomines was wore elevated during pregnancy, indicating higher parasitemic levels in this period. Only 17% of the studied women had two or more positive xenos during pregnancy. In these mothers the difference between the frequencies of positive xenos during and after gestation was high, suggesting the occurrence of exacerbation of infection at least in some women. PMID- 1308937 TI - [The current status of diffuse cutaneous leishmaniasis (DCL) in the state of Maranhao. II. The epidemiological and clinico-evolutionary aspects]. AB - The authors describe a retrospective and prospective study of 6 patients with diffuse cutaneous leishmaniasis observed in the state of Maranhao, since 1974. The patients come from different rural regions of the state and in all of them Leishmania (Leishmania) amazonensis was the cause five of the patients initiated their disease in the first decade of life. All the patients first had a solitary, nodular lesion, that after a variable period of time, disseminated and acquired other aspects. Sequentially the patients presented multiple nodular and ulcerative lesions, negative Leishmania skin tests and a refractory response to the therapeutic schedules used up to the present. PMID- 1308938 TI - Human immune responses during schistosomiasis mansoni. AB - Studies of immune responses as they occur in patients with schistosomiasis appear to progress relative to cUrrent technological advances, and to advance despite the understandable inability to pursue in vivo manipulations in this host/parasite system. Emphasis is most often placed on making immunological comparisons between such patient groups as reinfected/non-reinfected, intestinal/hepatosplenic, high/low intensities of infection, infected/uninfected within endemic areas, and those born of infected/uninfected mothers. Based on these types of comparisons, reasonable conjectures can be made regarding the immunological occurrences during this chronic exposure condition. Some consideration is now being given to the immune mechanisms of some of the observations made, and while some of these must then be carried back to experimental models for further manipulation-based analysis, new technological developments continue to assist in the field/bench ability to ask questions that might assist our understanding to a point where this knowledge can be applied to shaping developmental approaches to vaccine development and the goal of alleviating morbidity. PMID- 1308939 TI - [Sodoku--a case report]. AB - Rat-bite fever results from an infection with the organism Spirillum minus. The authors report a symptomatic patient with fever, malaise, and ulcer in forehead after a rodent exposure. The organism was identified in darkfield examination of the ulcer exudate. Penicillin was the drug used with clinical improvement of symptoms. PMID- 1308940 TI - HTLV-II and a new endemic area for HTLV-I in Brazil. PMID- 1308942 TI - [The noninterference of a Cary-Blair solution in the diagnosis of cryptosporidiosis by fecal examination]. PMID- 1308941 TI - Observations on potential tick vectors of human disease in the Cerrado region of central Brazil. PMID- 1308943 TI - [The evolution of chronic human chagasic cardiopathy in the interior of Paraiba state, Brazil in a period of 4.5 years]. PMID- 1308944 TI - The intestinal protozoology laboratory. PMID- 1308945 TI - [The neuropathological findings in the acquired immunodeficiency syndrome (AIDS): a review of 138 cases]. AB - This is an autopsy study performed in a retrospective fashion to determine the incidence of diseases that could affect the central nervous system in AIDS. For this purpose, 138 autopsies of patients with AIDS performed at the "Hospital de Clinicas de Porto Alegre", Brazil, between January/85 and December/90 were studied. All the brains were evaluated macroscopically and microscopically mainly through hematoxylin-eosin staining and if necessary special techniques like PAS, Grocott, Giemsa and Ziehl-Nielsen were done. Results have revealed 29 (21%) cases with cerebral toxoplasmosis; cryptococcosis in 17 (12%); tuberculosis in two (1%) and one case (0.7%) of candidiasis. Besides these inflammatory lesions, 15 (10%) presented vascular lesion; 8 (6%) had gliosis and 7 (5%) cases had suggestive findings of HIV encephalopathy. We can conclude that the CNS is a important target affected by AIDS and that cerebral toxoplasmosis is the principal disease in the CNS in AIDS patients. PMID- 1308946 TI - Fulminant hepatitis with microvesicular steatosis (a histologic comparison of cases occurring in Brazil--Labrea hepatitis--and in central Africa--Bangui hepatitis). AB - A similar histopathologic picture of fatal hepatitis associated with widespread acute fatty changes in hepatocytes and single-cell necrosis was seen in epidemic cases occurring in two distinct equatorial areas having high prevalences of HBV and HDV infections. The cases were previously considered to be two different entities; Labrea hepatitis in Brazil, and Bangui hepatitis in the Central African Republic. However, the histopathologic findings suggest that they are pathogenetically and etiologically related to HBV and HDV infections, probably modified by some as yet unknown factor(s) present in equatorial forest zones. PMID- 1308947 TI - [The use of sodium azide as a fecal preservative for studying the eggs of Schistosoma mansoni and of other helminths by the Kato-Katz method: a study in an endemic area]. AB - In two aliquots of 208 samples of stool, tests have been made by the Kato-Katz method, one being made after the use of 0.2mg of sodic azide for 200mg, and the other without the aforesaid conservant. The resulted percentages with or without the conservant were, respectively, for Ancylostomideos: 12.5 and 25.9; for Ascaris lumbricoides: 71.6 and 72.5; for Schistosoma mansoni: 7.6 and 17.7, and for Trichuris trichiura: 86 and 85. The count of the eggs with and without the conservant was, respectively, 264 and 539 for Ancylostomideos, 13186 and 33751 for A. lumbricoides, 55.5 and 63.5 for S. mansoni, and 1345 and 2068 for T. trichiura. The authors did not confirm the advantage of using sodic azide for study in endemic areas. They suggest that the exsiccation of the stool and the low intensity of infections can explain the unfavourable results of the present clinical trial. PMID- 1308948 TI - [Candidiasis in AIDS patients]. AB - A total of 35 in patients admitted at Emilio Ribas Hospital--Sao Paulo, Brazil, with digestive candidiasis and AIDS clinical diagnostic were evaluated 10 month later, being 29 male and 6 female; white outnumbering black with age ranged from 30 to 50 years old. Agar Sabouraud culture and tube germinative tests identified 28 (80%) Candida albicans out 35 strains. Minimum inhibitory concentration (MIC) 50% was against azoles (ketoconazole = 2.2 micrograms/ml; itraconazole = 21.0 micrograms/ml and fluconazole = 19.0 micrograms/ml); polyenes (nystatin = 50.0 micrograms/ml and amphotericin B = 0.12 micrograms/ml) and 5 fluorocytosine = 1.6 micrograms/ml. Siegel tests showed significant Candida albicans proportions in strains isolated from 35 AIDS patients. There was no significant relation between AMB doses and early or late death. CONCLUSIONS: candidiasis in AIDS patients showed high MIC 50% to azoles and nystatin and significant Candida albicans proportion in all strains isolated from AIDS patients. Previous amphotericin B therapy had no influence in early or late death in 30 patients. Previous therapy possibly explained MIC 50% increases in Candida strains. PMID- 1308949 TI - [The clinical parameters relevant for the differential diagnosis between mucocutaneous leishmaniasis and paracoccidioidomycosis]. AB - We retrospectively evaluated the medical records of 15 patients diagnosed with leishmaniasis and of 28 patients diagnosed with paracoccidioidomycosis presenting with involvement of the oral-nasal-pharyngeal mucosa seen at Escola Paulista de Medicina from 1986 through 1990. These patients were compared in regard to the following variables: sex, age, time since disease onset, location of lesion, and clinical complaints. Sex, time since disease onset, lesion at the nasal septum, palate, tongue, and lips, and history of oral pain, dysphagia/odynophagia, and nasal obstruction were significantly different in the two groups of patients. The authors point out to the relevance of these findings in the differential clinical diagnosis of leishmaniasis and paracoccidioidomycosis. PMID- 1308950 TI - [The prevalence of intestinal parasitoses among the users of the Health Center of Sousas District, Campinas, Sao Paulo (1986-1990)]. AB - The prevalence of intestinal parasites was carried on users of the Health Center of Sousas District, Campinas, SP (1986-1990). From 770 observed medical records we verify 114 positive cases (14.8%) for protozoa, helminths and commensals. Ascaris lumbricoides (48.2%), Giardia lamblia (30.7%), Trichuris trichiura (18.4%) and Enterobius vermicularis (9.6%) were more prevalent in preschool children. The adults, what are the most numerous class, appeared few parasitised. The other parasites and commensals appeared with a prevalence like the traditional brazilian population surveys, except for the absence of tenids and low prevalence of Ancylostomatoidea. We propose the realization of routine stool parasitological examinations among the preschool children and the use of the primary health care data in parasitological survey. PMID- 1308951 TI - [The prevalence, infection indices and feeding habits of the Triatominae captured in an area of epidemiological surveillance]. AB - Prevalence of triatomines and their infection by Trypanosoma cruzi, were studied during 1974-1981, in the Administrative Region of Campinas, Sao Paulo, Brazil. This investigation was continued (1982-1986), blood meal tests with bird, marsupial, rodent and human antisera having been added. Panstrongylus megistus, predominant in the region, whose winged instars are often found infected by T. cruzi in inhabited houses, displayed and alimentary eclecticism. From a sample of 7,785, 14.78 percent reacted positively with human antisera. A similar, but less marked behaviour was observed in Rhodnius neglectus. Triatoma sordida, the second most important species in the Region, was neither demonstrated to be feeding on humans nor to be infected by T. cruzi. Changes in their natural habitat probably caused sharp rises in T. arthurneivai populations in the human dwellings. The capture of three specimens of Microtriatoma borbai marks the first occurrence of this species in the State Sao Paulo. "Focus investigation" in areas in the surveillance phase can detect triatomines in the process of domiciliation. PMID- 1308952 TI - Serratia marcescens bacteremia associated with schistosomiasis mansoni. AB - The case of a 21-year-old man coming from rural Paraiba, northwestern Brazil, with schistosomiasis mansoni associated with Serratia marcescens bacteremia, is reported. His main complaints on admission were fever, diaphoresis and chills for ten days, and diarrhoea that lasted for four days. On physical examination he had jaundice and hepatosplenomegaly. Diagnosis of S. marcescens bacteremia was made by isolation of the bacterium in blood culture, and schistosomiasis was diagnosed by rectal and liver biopsies. This is the first time that the association of S. marcescens bacteremia and schistosomiasis mansoni is recognized. Although our case does not fit into the classic definition of prolonged bacteremia associated with schistosomiasis, it can be considered as a mild form of this association. With the improvement of medical assistance and laboratory facilities, early diagnosis of this association will be made more frequently, cases with short duration will be diagnosed few days after the start of the symptoms, and classic prolonged cases will become rarer. PMID- 1308953 TI - [Pulmonary lymph node in acute juvenile paracoccidioidomycosis (a case report)]. AB - The primary complex like Ghon was observed in a child's clinical roentgenographic study. C.S., white, male, 6 years old, was born in Curitiba (PR), Brazil and living in Guaratingueta (SP), Brazil, developed "common cold", bimodal diary fever, chills, shake and sweats. Dyspnea, cough with general lymphadenopathy. Foot and right shoulder arthralgias. Six months ago visited a cave, equitation practice, dog and cat contacts and no transfusion, frontal sweats, fever (38.4 degrees C). T.A. was 8/6, tachycardia in generalized lymphadenopathy. Cardiopulmonary system was normal, mesogastric tumoral mass, hepatosplenomegaly and no ascites. Bone marrow with eosinophilia; nodule demonstrated presence of P. brasiliensis, hypoalbuminemia; hyperglobulinemia; anemia; leukocytosis with eosinophilia. Immunodiffusion with exoantigen 43 kd of P. brasiliensis was 1/32. Primary complex like Ghon was observed in interstitial pneumonia followed by mediastinal and mesogastric mass (35 to 40 days). Clavicular osteolytic lesions (45 to 60 days) appeared during paracoccidioidomycosis therapy. Recovery was observed 2 months after treatment of acute infantile paracoccidioidomycosis. PMID- 1308954 TI - [The single health system: a unique opportunity]. PMID- 1308955 TI - [Teaching about mishaps with venomous animals in the medical schools of Brazil]. PMID- 1308956 TI - [The weak performance of albendazole in the treatment of strongyloidiasis]. PMID- 1308957 TI - Serum bile acids in schistosomotic hepatic fibrosis. PMID- 1308958 TI - Hypoparathyroidism in chronic alcohol intoxication: a preliminary report. AB - It is well known that osteoporosis is more common in chronic alcoholists than in age-matched controls. Possible aetiological factors could be: malabsorption of calcium and vitamin D, liver disease, abnormal parathyroid function. With this study, the authors investigated parathyroid hormone (PTH) behaviour in thirteen selected patients with alcohol abuse, free from any clinical or humoral sign of hepatopathy, and in ten healthy subjects as a control group. In alcohol abusers a significant reduction of plasmatic PTH, compared to normal calcium levels were found. A possible direct interaction effect between ethyl alcohol and PTH may be suggested, even if further studies are required. PMID- 1308959 TI - [The IgE system]. AB - The IgE synthesis is regulated by a system of immunocompetent cells (B and T lymphocytes) and cytokines (IL-4, IFN gamma, IL-2, IL-5, IL-6) produced by T cells as a response to antigenic stimuli. IL-4 alone, or associated with other cytokines, determines the CD23+ receptor (FCERII) expression on monocytes macrophages, eosinophiles, platelets, epidermidis Langerhans cells and B lymphocytes surfaces, inducing its cleavage in a Soluble Factor (IgE-BF), that increases the IgE synthesis. IFN-gamma, on the other hand, plays an inhibitory role on T-dependent phenomena, IL-4-mediated. In patients affected by atopic diseases, associated with oculorhinites, dermatitis and hyper-IgE syndrome, are found high serum levels of IgE, eosinophiles, and a large number of CD23+ cells: this indicates the hyper-reactivity of the IgE system and the IL-4 overproduction. PMID- 1308961 TI - [Coexistence of a molar pregnancy and a live fetus]. AB - The authors are presenting the second reported case of molar pregnancy with a coexistent fetus in which the outcome of both fetus and mother was positive. The diagnosis has been determined in utero as seen in the previously case presented. After a careful examination of world literature, we have accurately evaluated the elements which need to be taken into consideration in order for the pregnancy to progress. PMID- 1308960 TI - Role of arterial hypertension in plasma secretion of prostacyclin during renal failure in man. AB - Cardiac function and morphology in chronic hemodialyzed patients are modified in consequence of both vascular and neurohormonal factors. In the present study we investigate on the role of prostacyclin (PGI2) vasodilator agent, during hemodialytic (HD) treatment. Twenty-four patients (13 males and 11 females; 9 hypertensive and 15 normotensive) aged 58.5 +/- 14.4 years were studied; 2.5 ml of venous blood were collected before (time 0) and 15', 120', and 240' of dialytic session. The PGI2 levels were measured in plasma, after extraction in ethyl acetate by RIA method, as levels of 6-Keto-PGF1 alpha, a stable metabolite. The results have shown as increase of PGI2 levels at 15' in hypertensive HD patients (HHD) from the begin of dialysis that increased until 240'. This phenomenon was more significant in hypertensive than in normotensive group (NHD) (p < 0.05 vs NHD). These preliminary data suggest that in HHD patients the role of PGI2 is more important than in NHD patients as regards the effects on regulation of circulatory tone. The increment of PGI2 levels could be in relation with the sympathetic activation occurred during hemodialytic treatment. PMID- 1308962 TI - [Variations in lymphocyte subsets in chronic inflammatory and neoplastic pathology in the elderly. II. Discriminant stepwise analysis]. AB - The variations of lymphocyte subsets in chronic inflammatory and neoplastic diseases in an elderly population, have been previously reported. The different behavior of all the subsets that had shown significant variations of frequencies and absolute values within the groups with the Multivariate Analysis of Variance, have been studied. The use of the Discriminant Stepwise Analysis has given the chance to spot the discriminant subsets and their ability in discriminating the inflammatory and the neoplastic groups from each other and from the controls and finally in pointing out all the subsets which did not affect such differentiation. PMID- 1308963 TI - [Operative risk in the elderly patient: protocol for evaluation]. AB - Authors emphasize the surgical risk in elderly. Mortality and morbidity are pointed out in male and female patients. They report on 30 aged patients operated for various pathologies also discussing the results. PMID- 1308964 TI - [Acute enterorrhagia in a young adult: emergency treatment]. AB - A case of enterorrhagia sustained by arteriovenous malformation of the caecum in a young patient is reported. The importance of an early diagnosis to avert a serious anemia is underlined. Preminent role of colonscopy and selective visceral angiography in the diagnosis of such disease is discussed. At first a conservative urgently treatment of caecum bleeding is advised. Subsequently, when the patients is in more favourable conditions, an elective surgical operation is considered as essential. PMID- 1308965 TI - [Epidemiology and clinical presentation of vulvar cancer]. AB - Recently, we observed a lowering in the average age of women affected by vulvar cancer. Five years after the diagnosis, survival is little more than 50%. Such a severe prognosis is caused both by a late diagnosis and organization lacks of prevention. Etiology and symptomatology of vulvar cancer are widely treated; particular prominence is given to the differential diagnosis. PMID- 1308966 TI - [The effectiveness of enoxacin for the treatment of complicated urinary tract infection]. AB - In this study we evaluated the efficacy of enoxacin in treating complicated urinary tract infections (UTI). We isolated 21 bacterial strains from 20 enrolled patients and all the strains showed "in vitro" susceptibility to enoxacin. The most represented bacterial strain was E. coli (47.7%). After 48 hs and after 30 days from the end of the treatment, we observed clinical and bacteriological recovery in 65% and 55% of the patients, respectively. However, 6 out of the 20 patients (30%) interrupted the treatment due to mild-severe side effects. In conclusion, enoxacin showed a good antibacterial activity, but it could be necessary to lower daily dosage and to extend the treating period to prevent side effects. PMID- 1308967 TI - [Lower back pain in physicians. Epidemiological aspect and risk factors]. AB - The purpose of this study was to evaluate as accurately as possible, in a well defined population subgroup, the prevalence and incidence of lower back pain, the impact of this symptom on professional activities and personal life, and the influence of risk factors. Members of the medical profession were considered particularly apt to accurately and reliably report their personal experience with lower back pain and were therefore selected for this survey. Five hundred 93-item questionnaires were sent to a representative sample of physicians in the Maine-et Loire district, France. Response rate was 93%. Prevalence of lower back pain at the time of the survey was 32% and cumulative prevalence was 62%. Static spinal disorders (exaggerated lordosis, scoliosis, unequal length of lower limbs) and injury to the spine were found to be risk factors. Occupation-related stresses to the spine reported as being responsible for lower back pain included bending forward for prolonged periods, lifting weights, driving, and prolonged sitting. PMID- 1308968 TI - [Immunosuppressive therapy of secondary amyloidosis associated with rheumatoid arthritis or Still's disease]. AB - Ten cases of renal amyloidosis associated with rheumatoid arthritis (n = 9) or Still's disease (n = 1) were studied retrospectively. One patient had end-stage renal failure at first presentation, whereas the nine others had nephrotic syndrome without renal failure as the initial manifestation of amyloidosis. In the three untreated patients, renal function deteriorated steadily and dialysis was rapidly necessary. In contrast, among the six patients given chemotherapy, four had normal renal function under therapy. These favorable therapeutic results are analyzed and compared with previously published data on the treatment of secondary amyloidosis. PMID- 1308969 TI - [Evaluation of cardiac involvement in systemic lupus erythematosus. Clinical and echographic study]. AB - Thirty-five consecutive patients with systemic lupus erythematosus were enrolled in a prospective study. Investigations included a physical evaluation, tests for antinuclear antibodies and antiphospholipid antibodies, an electrocardiogram, a plain chest film, a 2D echocardiogram and a Doppler study. Clinical cardiac manifestations and alterations of the electrocardiogram were infrequent (17% and 11% of patients, respectively) and no patients had abnormal chest film findings. In contrast, echocardiographic abnormalities were common (82% of patients), although moderate in most instances. Pericardial involvement was found in 15 patients (42.8%); a pericardial effusion was seen in 9 of the 14 patients with inactive disease (p < 0.003), whereas thickening of the pericardium was visible in 4 patients with active disease and 2 of the 21 patients with inactive disease. Valve abnormalities were found in 17 patients (48.5%), but were not related to the presence of antiphospholipid antibodies; valve alterations included verrucous endocarditis in one case, valve thickening in one case, mitral prolapse in five cases, and mild or moderate regurgitation in 15 cases (aortic in 2 cases, mitral in 7 cases, pulmonary in 3 cases and tricuspid in 7 cases). Alterations in ventricular chamber size and kinetics were also fairly common, albeit of uncertain pathogenetic significance. These data confirm the value of 2D echocardiography for identifying and monitoring cardiac involvement in systemic lupus erythematosus, even in patients with no overt clinical manifestations. PMID- 1308970 TI - [Degenerative spinal disease in an outpatient clinic in Lome (Togo)]. AB - A survey was conducted to determine the frequency and semiological characteristics of degenerative spinal disease in patients attending a hospital rheumatology outpatient clinic in Lome, Togo. Seven hundred and one of the 1,821 patients seen over a two-year period had degenerative spinal disease. Spinal disease included lower back pain (n = 385), lumbar and radicular pain suggestive of disk protrusion (n = 137), lumbar and radicular pain with claudication suggestive of stenosis of the spinal canal (n = 42), dorsal pain (n = 24), cervical pain (n = 68) and cervical and brachial pain (n = 45). Clinical patterns were similar to those seen in Western countries. However, lumbar and radicular pain with claudication suggestive of stenosis of the spinal canal occurred at a younger age and mainly affected females. These data are in contrast with previous studies suggesting that lumbar and radicular pain due to disk protrusion and stenosis of the spinal canal are uncommon in Black Africa. PMID- 1308971 TI - [Long-term results of chymopapain chemonucleolysis]. AB - Results of chemonucleolysis were evaluated (on the basis of residual pain, occupational activities, physical activities, and use of analgesics) in 125 of 162 consecutive patients with lower back pain and sciatica associated with documented vertebral disc protrusion who were managed and followed up for at least five years. Results were satisfactory in 62% of patients. Among 82 patients evaluated during a follow-up visit, 30% were free of symptoms, 38% had lower back pain, and 30% had radicular pain; however, among symptomatic patients, 67% had no limitations of activities of daily living. Results were significantly less favorable in power drill workers and in patients who had chemonucleolysis at the L4-L5 level. These data are evidence that chemonucleolysis provides good long term results. PMID- 1308972 TI - [Ulnar nerve lesion at the elbow. Epidemiological, clinical and electromyographical data. Apropos of 312 patients]. AB - Four hundred and ninety-three electromyographic ulnar nerve lesions identified in 312 patients were reviewed. During the same period, 1,000 cases of median nerve entrapment were seen in the same department. Among ulnar nerve lesions, 84% were idiopathic and only 52% were responsible for clinical symptoms. In patients with symptoms, three main patterns of paresthesia were seen: exacerbation at night and/or in the morning upon awakening (39%), permanent isolated paresthesia (34%), and permanent paresthesia with exacerbation at night and/or in the morning upon awakening (27%). Objective sensory loss was found in 1/3 to 1/4 of cases. All patients with muscle wasting (11%) also had sensory loss; muscle strength was markedly decreased in 19% of patients. Pain was mild and infrequent (35%). Electromyographic studies revealed a decrease in motor and sensory conduction velocity at the elbow (mean value 36.2 m/sec). Sensory conduction velocity was the most sensitive parameter for detecting incipient or moderate forms, whereas motor conduction velocity was extremely helpful in severe forms. Eighty-three per cent of patients had alterations of both conduction velocities (sensory and motor). In the mildest forms, nerve conduction velocity was normal (13% of cases); in these patients diagnosis was established on the basis of either a partial motor conduction block (3%) or desynchronization of the sensory action potential (10%). PMID- 1308973 TI - [Different methods of bone filling in orthopedic surgery]. PMID- 1308974 TI - [Biomaterials for the locomotor apparatus]. PMID- 1308975 TI - [Dermatomyositis associated with two neoplasms]. AB - A case of dermatomyositis in a patient with two different malignancies is reported. Skin lesions cleared only following exeresis of the second tumor. This case provides the opportunity for a discussion of the main theories put forward to explain relationships between dermatomyositis and malignant disease. PMID- 1308977 TI - [Cost of sciatica]. PMID- 1308976 TI - [BCG osteoarthritis on knee prosthesis after intra-vesical BCG therapy]. AB - A case of Calmette-Guerin bacillus (BCG) infection of a knee implant during intravesical BCG-therapy is reported. The course was favorable after replacement of the implant and administration of antituberculous agents. This case of septic osteoarthritis due to the BCG is different from cases of reactive polyarthritis reported after intravesical instillations of BCG. It probably resulted from diffusion of the BCG via the bloodstream. PMID- 1308978 TI - [Association of Crohn disease with joint manifestations and malignant lymphoma]. PMID- 1308979 TI - [Rheumatic diseases associated with HIV infection]. PMID- 1308980 TI - [Sternoclavicular hyperostosis and psoriasis]. PMID- 1308981 TI - [Continuous Hallopeau acrodermatitis with osteolysis preceding common psoriasis with oligo-arthritis by 35 years]. PMID- 1308982 TI - Acceptance of the George M. Kober Medal. PMID- 1308983 TI - Presentation of the George M. Kober Medal to E. Donnall Thomas. PMID- 1308985 TI - Association of American Physicians. PMID- 1308984 TI - 1992 Presidential Address. Association of American Physicians. Mission: the advancement of scientific and practical medicine. PMID- 1308986 TI - Endothelial cell heme oxygenase and ferritin induction by heme proteins: a possible mechanism limiting shock damage. AB - Acutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes. PMID- 1308987 TI - Transcriptional activation of fibroblast stromelysin-1 and collagenase gene expression by a novel lymphokine, leukoregulin. PMID- 1308988 TI - Isolation and characterization of a novel streptococcal superantigen. AB - The involvement of S. pyogenes (group A Streptococcus) in severe invasive disease, toxic-shock-like syndrome, and episodes of rheumatic fever led us to explore the possibility that these strains produce a novel superantigen. By using a superantigen-specific assay, we purified a 28-kDa protein from culture supernatants that stimulated T cells in an MHC class II-dependent, V beta specific manner and designated it SSA, streptococcal superantigen. The amino terminus of SSA showed striking resemblance to SEB, SEC1, and SEC3. The structural homology exhibited by SSA to SEB was reflected functionally in that both of these superantigens bound the same class II isotypes. In contrast, SSA differed from SEB and other known bacterial superantigens with respect to its pattern of V beta-specific T-cell activation. SSA stimulated human T cells that expressed V beta 1, 3, 15, and perhaps V beta 5.2. Using SSA-specific antibodies in an immunoblot assay, we screened 26 strains of Lancefield group A Streptococcus and 16 strains of group B, C, and G Streptococcus. We found that SSA was expressed with high frequency in group A strains, but was absent from all other groups tested. These data establish SSA as a novel superantigen secreted by S. pyogenes. Further study of the structure and expression of SSA may reveal a role for this molecule in current episodes of severe streptococcal diseases. PMID- 1308989 TI - Adrenal renin is released into the circulation of the hypertensive transgenic rat TGR (mRen-2)27. PMID- 1308990 TI - Iron absorption via the mucin-integrin mobilferrin pathway. PMID- 1308991 TI - In vivo platelet activation in homozygous cystathionine beta-synthase deficiency: a probucol-sensitive phenomenon. PMID- 1308992 TI - Differential utilization of translation initiation sites in alternatively spliced mRNAs arising from the protein 4.1 gene. PMID- 1308993 TI - ADP-ribosylation factor, a guanine nucleotide-binding protein activator of cholera toxin, is isolated in an activated state when expressed as a fusion protein in Escherichia coli. PMID- 1308994 TI - Recombinant vaccinia virus with influenza hemagglutinin protects old mice from influenza infection. PMID- 1308995 TI - A Trypanosoma cruzi DNA sequence amplified from inflammatory lesions in human chagasic cardiomyopathy. PMID- 1308996 TI - Interleukin-8 induces neutrophil accumulation in the trachea of allergic dogs. PMID- 1308997 TI - Derivation of pluripotential embryonic stem cells from the rabbit. PMID- 1308998 TI - Mutations in the insulin receptor and their effect on glucose transport. PMID- 1308999 TI - Human Fc gamma RII: the structure of the Fc gamma RII cytosolic domain governs phagocytic function. PMID- 1309000 TI - The human testis: a novel locus for thyrotropin-releasing hormone (TRH) and TRH mRNA. PMID- 1309001 TI - Role of kallikrein-kinin system in the pathogenesis of bacterial cell wall induced inflammation and enterocolitis. PMID- 1309002 TI - Effects of adherent bone marrow stromal cells on the development and proliferation of highly purified human hematopoietic stem cells. PMID- 1309003 TI - Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease. AB - Cloning and expression of the defective genes for ALAD from a patient with inherited ADP were carried out. Two separate point mutations, termed G1 and G2, resulting in a single amino acid change in each ALAD allele, were identified. The G1 mutation (C718-->T) occurred in the allele within the substrate-binding site, producing an Arg240-->Trp substitution; the G2 mutation (G820-->A) occurred downstream of this site in the other allele, resulting in an Ala274-->Thr substitution. Using RT-PCR, the mother, the brother, and the sister were shown to have the G1 defect. Expression of the G1 cDNA in CHO cells produced ALAD protein with little activity; the G2 cDNA produced the enzyme with approximately 50% normal activity. Pulse-labeling studies demonstrated that the G1 enzyme had a normal half-life, while the G2 enzyme had a markedly decreased half-life. These data thus define two separate point mutations, one in each ALAD allele, as well as the altered properties of the two enzymic proteins encoded by the mutant genes in this patient. PMID- 1309004 TI - Large numbers of alternatively spliced isoforms of the regulatory region of human erythrocyte ankyrin. PMID- 1309005 TI - The platelet-activating factor acetylhydrolase from human plasma prevents oxidative modification of low-density lipoprotein. PMID- 1309006 TI - The molecular basis of glucocorticoid-remediable aldosteronism, a Mendelian cause of human hypertension. PMID- 1309007 TI - The interaction of Ly-49 with H-2Dd globally inactivates natural killer cell cytolytic activity. PMID- 1309008 TI - Human epsilon mRNAs using membrane sequence encode for two membrane forms of IgE and a novel second secreted IgE. PMID- 1309009 TI - Compartmental analysis of RBC circulation through the rabbit kidney. AB - This experiment involved 12 rabbits of both sexes, weighing 2.1 kg. After anesthesia, the kidneys were exposed, isolated and cannulated in the renal artery, ureter and sometimes in the vein as well. The kidney were perfused through the renal artery with Krebs-Henseleit solution, which were then filtered to be free of particles, gased with 95% O2-5% CO2, and kept at 37 degrees C. We measured RBCs concentrations by means of Coulter Counter in the venous outflow collected, and plotted them against the volume perfused. Using 2 different flow rates, 9 ml/min (group I) and 19 ml/min (group II), we found that the RBCs decreased in a multiexponential decay fashion and a biophysical model for each flow rate was constructed. These models indicated that there were more cell stores (2.20 x 10(10)) in the fast compartment of group II than in group I (1.72 x 10(10)). This difference is not statistically significant, but certainly coincides with urine flow collected from ureter cannula during perfusion. Our present data clearly suggest that in order to clear 99% blood cells out of 10-12 gm rabbit kidneys, at least 3-6 ml of cell free perfusate is required while clearing the whole blood cells out of human kidneys (200-240 gm) may need 600 ml or more. Thus, we recommend that at least 600 ml of perfusate should be used to clear most of the blood cells in the renal vasculature before renal transplantation is performed. PMID- 1309010 TI - Morphological evidence of pulmonary vascular leakage through gaps observed with casting methods and S.E.M. AB - We have used selective casting methods to separate pulmonary elastin from vascular elastin in the lungs of rabbits, dogs and pigs. The lungs are digested with 0.1 N NaOH at 75 degrees C for 24 approximately 48 hours with frequent turning as the lungs are filled with air to about 80% of the vital capacity prior to the casting which is done at pressure of 20 approximately 50 mmHg. After vascular injections, we saw many small globular bits of casting material well separated from cast vessels and lying in the pulmonary elastin. Surface forces should make the casting material creep along the vessels even if they are not completely filled, so that the spherical shape is the one expected if the case is extruded into the parenchymal space and the air space. We conclude that this suggests that the pulmonary circulation is partially and temporarily 'open' as seen in the spleen and some other organs, rather than a completely 'closed' one as is generally accepted. At least some of these extravasations may be associated with lymphatics, although we have not proved this. PMID- 1309011 TI - Effects of hypotensive anesthesia with sodium nitroprusside or isoflurane on hemodynamic and metabolic changes. AB - The hemodynamic and metabolic changes during induced hypotension with isoflurane (isoflurane group) or sodium nitroprusside (SNP group) were observed in twelve mongrel dogs. These hypotensive effects were evaluated at 30 and 60 minutes after the mean arterial blood pressure was lowered to 50% from the control. Hemodynamic changes were evaluated by measuring systemic arterial blood pressure, heart rate, central venous pressure, pulmonary capillary wedge pressure, cardiac output, systemic vascular resistance and pulmonary vascular resistance. Metabolic changes were evaluated by measuring serum lactate and pyruvate, arterio-venous oxygen content difference and oxygen extraction rate. We also compared the ventilatory effect of hypotensive anesthesia by blood gas analysis. The results were as follows: 1. Isoflurane inhalation 2-4% or SNP infusion 10-20 micrograms/kg/min was required to reduce the mean arterial pressure to 50% of the control. 2. Heart rate was decreased slightly in the isoflurane group but significantly decreased in the SNP group. 3. There were no significant changes in central venous pressure and pulmonary capillary wedge pressure in either group. 4. Cardiac output was reduced in both groups but was more severe in the isoflurane group. 5. Systemic vascular resistance was decreased by 36% in the isoflurane group and 47% in the SNP group. 6. Acidosis was apparent and did not recover to the control until 30 minutes after recovery in the SNP group. 7. Arterio-venous oxygen difference was increased during hypotension in the isoflurane group probably due to decreased cardiac output. 8. The lactate/pyruvate ratio increased slightly in the SNP group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309012 TI - Clinical analysis of 34 diffuse axonal injured (DAI) patients below GCS 8. AB - A consecutive series of 34 severe head-injured patients (DAI) were studied prospectively. Patients were categorized according to a new, simple classification system comprised of four lesion types according to the compression or obliteration of the ventricles or cisterns. Five patients belonged to type II and 19 patients to type IV. Each type was further subdivided into two GCS score ranges (5 to 8 and below 5). The distribution of the posttraumatic infarction was mainly in the frontal and temporal lobes (60% of all cases). Our data demonstrated that the ICP was significantly lower at a 30 degrees head elevation than at 0 degree (18.6 +/- 7.21 mmHg vs 23.0 +/- 10.60 mmHg. t = 4.22 P < 0.001), but head position did not statistically affect CPP (69.4 +/- 19.86 mmHg vs 68.2 +/- 19.87 mmHg. t = -0.54, P < 0.59). The effect of intensive therapy on ICP, CPP and AVDO2 was studied in all cases, employing steroids and diuretics in a modified intensive care scale. In cases where barbiturates were employed, there were statistically significant changes in ICP and AVDO2 (P < 0.001), but CPP was not affected (P < 0.59). Surviving patients were analyzed by using the GOS and the neurological grading score (NGS, Nihon University) of the persistent vegetative state. Our data suggests that head elevation of 30 degrees and barbiturate therapy are more effective on ICP and AVDO2, and NGS more exact than GOS in vegetative patients. PMID- 1309013 TI - Development of elastin layers in the aortic wall of human fetuses. AB - The presence of elastin layers in the aortic walls of twelve human fetuses was confirmed with scanning electron microscope pictures after hot alkali treatment and histochemical examination. In addition, the number of elastin layers in aortic walls of 5 different segments were compared in fetuses of varying ages. Aldehyde fuchsin stained slides of elastin ascending aortas showed a range between 27 and 55 layers of elastin in fetuses of 8 weeks to 32 weeks. However, in the lower abdominal aortas, elastin layers decreased from 28 to only 3 layers for fetuses of the same age. Furthermore, as elastin layers decreased from ascending aorta to abdominal aorta with the progression of fetal life, similar changes in the elastin lamellae were observed. These results suggest that while aortas grow rapidly in length, the medial elastin thickens slowly, perhaps due to slow development of hydrodynamic forces and pressures. Also the adventitial elastin appears to lose out gradually along the length from ascending aorta to abdominal aorta. PMID- 1309014 TI - Culture of melanocytes obtained from normal and vitiligo subjects. AB - The development of human melanocyte culture in vitro from normal adult skin and uninvolved skin of vitiligo patients is essential to investigate the mechanism of depigmentation in vitiligo and other pigmentary dermatoses. By using selective growth and long-term maintenance conditions, we selectively cultured melanocytes derived from normal foreskins and arm skins, and uninvolved foreskins and arm skins of vitiligo patients. The melanocytes of the arm skins were successfully cultured from the roofs of suction blisters. Melanocyte Growth Media (MGM) consisting of MCDB-153 formulation with basic fibroblast growth factor (bFGF), bovine pituitary extract (BPE), insulin, hydrocortisone, phorbol 12-myristate 13 acetate (PMA) and 10% human AB serum was sufficient to grow the melanocytes from normal and vitiligo donors. Melanocytes from uninvolved skin of vitiligo donors showed no different morphologic features, initial seeding capacity and population doubling time compared with those from normal skin. Melanocytes from both cell types grew without any lag period for more than 6 months (6-11 passages). Melanocytes obtained from foreskins had higher initial seeding capacity and shorter population doubling time than those obtained from arm skins using suction blistered roofs. Our results suggest that the culture method using suction blisters may be a simple and easy way to obtain melanocytes. In addition, vitiligo melanocytes can be successfully cultured with appropriate growth conditions and may show no defective growth patterns. This culture system will be applied to investigate the basic pathophysiology of vitiligo and other various pigmentary dermatoses. PMID- 1309015 TI - Electron microscopic study of the cases of minimal change nephrotic syndrome with mesangial IgA deposition. AB - Twenty-five cases of minimal change nephrotic syndrome(minimal change disease, MCD) with mesangial IgA deposition were evaluated electron microscopically. The thickness of the glomerular basement membrane(GBM) was 3875 +/- 1271 A and 3056 +/- 1201 A in adults and children, respectively. Alteration of the GBM was noted in 3 adults and eight children: splitting in 4, focal thinning in one, widening of the lamina rara interna in 10, and widening of the lamina rara externa in 4 cases. Minimal mesangial electron dense deposits were found in all but one adult, and an increase of the mesangial matrix and minimal mesangial proliferation were observed in 8 and 6 cases, respectively. Electron microscopic findings show representative findings of MCD in our cases. A relationship between the GBM alterations in these cases and frequent association of hematuria is suggested and discussed. PMID- 1309016 TI - Arthroscopic subacromial decompression. AB - A study group composed of 11 shoulders in 10 patients underwent arthroscopic subacromial decompression for impingement syndrome. There were no biceps tendon ruptures, acromioclavicular arthritis or glenohumeral instability. Eight men and two women ranging in age from 17 to 65 years (mean age 38.7) with dominant arm involvement in 9/10 were evaluated for an average follow-up of 19.4 months (range 12-26) postoperatively. Based on the University of California at Los Angeles shoulder rating scale, nine (82%) shoulders had satisfactory results and the remaining two (18%) had unsatisfactory results. This is a preliminary report of our early experience in this rather new method of treatment, but the results are encouragingly good. PMID- 1309017 TI - Congenital absence of gallbladder. AB - Nine surgically proven congenital absence of gallbladder (CAGB) cases were reviewed. All of them had one or more kinds of biliary symptom. Tests such as abdominal ultrasonography, intravenous or oral cholecystography and even endoscopic retrograde cholangiography not only failed to predict CAGB but misleadingly indicated other similar conditions. Only the abdominal computed tomography (CT), performed on one patient, enabled the accurate diagnosis of CAGB. All the patients underwent abdominal exploration, and CAGB was confirmed by the meticulous dissection of the entire extrahepatic biliary tree and the operative cholangiography. Five patients had concomitant biliary pathologies responsible for their symptoms, but four patients had isolated CAGB. CAGB is a rarely encountered condition for a clinician, but extensive diagnostic work-ups including abdominal CT should be performed in all situations where CAGB is suspected. Thus unnecessary exploration can be avoided in the isolated CAGB case. PMID- 1309018 TI - Thyrotropin-secreting pituitary microadenoma. AB - We present a 45-yr-old male with clinical signs and symptoms of mild hyperthyroidism, high serum levels of T3, T4, and FT4 as well as serum TSH concentration. The elevated alpha-subunit level and alpha-subunit/TSH molar ratio were also observed. These findings indicated the presence of hyperthyroidism due to inappropriate secretion of TSH, whose neoplastic origin was documented by nuclear magnetic resonance scan showing a 0. 6 cm pituitary adenoma. Selective pituitary adenomectomy was completely successful; alpha-subunit, TSH, T3, T 4, and FT4 normalized, and euthyroidism was restored. Light microscopic immunohistochemistry showed that the adenoma was composed of TSH-secreting cells. PMID- 1309019 TI - Tuberculosis of the ribs: a recurrent attack of rib caries. AB - Rib tuberculosis is an extremely rare condition with the incidence not exceeding 3 percent of all skeletal tuberculosis. The authors experienced a recalcitrant case of pulmonary tuberculosis accompanied by chest wall cold abscesses involving ribs recurring at a new site in approximately 10 months despite of medical and surgical treatment. The patient has twice taken thoracotomy for abscess drainage and during the second thoracotomy, a partial resection of involved ribs was performed. PMID- 1309020 TI - [Tobacco use and the Third World: a problem of mental health]. PMID- 1309021 TI - [Nosology, genetics, neurobiology, and psychopharmacology of schizophrenia]. AB - The development of psychiatric nosology is outlined, and five principles responsible for the organization of psychopathologic symptoms into psychiatric disorders are proposed. Within the frame of reference of the nosologic organizing principles, the evolution and dissolution of the unitary concept of schizophrenia are reviewed, and some of the findings in neurobiologic, genetic and psychopharmacologic validation studies are discussed. It is suggested that findings in family genetic studies and in clinical psychopharmacologic investigations are supportive of Leonhard's (1957) contention that systematic and unsystematic schizophrenia are two distinct populations. PMID- 1309022 TI - [Women: psychopathology and cultural malaise]. AB - An account of the incidence of mental health and disease criteria in feminine psychopathology is presented as well as a consideration on the increasing medicalization and psychiatrization of women's demand for sanitary help. Symptoms should not be understood separately from the discontent relevant to the place femininity is given in society--hence women's subjective suffering. Observes Freud that, as a child bearer, a woman is more involved with sexual functions- thus placing her at the pulsional pole of culture which reduces a propitiatory space for sublimation processes. Correlatively, Freud sees women as victims of the worst social repression process: women being forbidden to think. Even though discontent, and psychic pain cannot be avoided inasmuch as civilization imposes certain restrictions necessarily, there is, however, an excess of pain related to the feminine position. No cure will be possible if women fail to restore their own place as subjects of their own desire, whose alienation is shown through symptoms. PMID- 1309023 TI - [Mental disorders in Nicaragua: family perspective]. AB - In recent years the family perspective in Psychiatry has become more important a factor. Therefore this paper is aimed at examining the family structure of mentally disordered people in Leon, Nicaragua, as well as presenting the use of a Genogram in epidemiological research. 201 families were randomly selected, whose members were interviewed in two steps: a screening, and a diagnostic stage. The family map or Genogram for each family was analyzed with respect to adult and child cases, generations within the family, and other background variables. PMID- 1309024 TI - [Widows of victims of Nazi concentration camps: their pathology]. AB - The psychosocial situation of widows and orphans of victims of the Nazi concentration camps in Poland are presented. In 1984, 74 widows of victims from the Auschwitz-Birkenau camp were interviewed. This article describes widows' emotional-behavioral reactions when facing the imprisonment and death of their husbands, their difficulties in adapting themselves to widowhood, different adaptative forms of memories of their married life, and consequences relevant to widows' mental health and family, and social consequences of widowhood. PMID- 1309025 TI - [Proposal of a model of a mental system based on mental functions]. AB - Based on the mental functions according to classical physiological criteria, the authors propose an information management system with heuristical value for Psychiatry. This system assumes that information will be received by the sensoperceptual area, being analyzed within both the cognitive and affective areas later on, the analysis output thus taking place through the psychomotor area. Such a system allows a theoretical structure -correlating some aspects of Neurosciences with psychiatric clinical events, to be elaborated. Furthermore, such a system allows mental disorders to be understood as disturbances in the information processing the nervous tissue performs. PMID- 1309026 TI - [Comparative psychosocial study of social values]. AB - A culturally readapted scale of the classical Rokeach scale was applied to a 200 subject sample. Subjects were male and female workers on the one hand, and university men and women, on the other hand. The results of the different subsamples were compared by means of statistical techniques. Later, the same comparison was carried out with data from a similar study performed in Venezuela. PMID- 1309027 TI - [Factors associated with the failure to use condoms among a population of parenteral drug addicts]. AB - Use of condom in sexual intercourse by intravenous drug users has been assessed among a clinical population (n = 139). The multiple logistic regression results show that being a female (OR = 5.1, 95% CI = 2.0-13.2), on drug dependence for a 5-year period or more (OR = 3.0; 95% CI = 1.3-6.9) correlates with non-condom use. Less than 25% of females use condom in their sexual contacts. On the contrary a higher educational level seems to protect subjects against non-condom use (R = 0.3; 95% CI = 0.1-0.8). The most parsimonious model fitting to data at hand includes such variables as sex, educational level, partnership and frequency of sexual intercourse, as well as years on addiction. Other set of variables such as living and working status, age, and previous sexually-transmitted diseases experience are not required for the final model. Emphasis is placed on the need for developing programs aimed at modifying the high risk behavior intravenous drug users resort to in their sexual intercourse, stressing that the main dissemination cause of the human immunodeficiency virus among such a population is due to their sharing drug injections equipment. PMID- 1309028 TI - Twenty-five years of the Gaubius Institute. PMID- 1309029 TI - Vascular permeability factor, fibrin, and the pathogenesis of tumor stroma formation. PMID- 1309030 TI - Fibrin and its derivatives in the normal and diseased vessel wall. PMID- 1309031 TI - The response of the vessel wall to thrombosis: the in vivo study of venous thrombolysis. AB - The vessel wall is the site of synthesis and regulation of the fibrinolytic system, and this delicate process is overwhelmed by occlusive thrombosis in veins. The endothelium may or may not survive thrombus formation, but has strong powers of regeneration, and is subsequently vital to the process of recanalizing the vessel. The endogenous fibrinolytic response to venous thrombosis is not well delineated but appears to involve both the newly formed endothelium within and beneath the organizing thrombus, together with an increase in tissue plasminogen activator synthesis or storage in distant uninvolved veins. The further use of thrombus models in which the endothelium is not definitely damaged should enable greater understanding of its role. Immunocytochemistry and in situ hybridization may be helpful in defining some of the unanswered questions. PMID- 1309032 TI - The role of protected extracellular compartments in interactions between leukocytes, and platelets, and fibrin/fibrinogen matrices. AB - Polymorphonuclear leukocytes express multiple surface receptors that mediate their adhesion to extracellular matrices and to other cells. These receptors also play roles in cell migration and phagocytosis. We have studied the role of one class of polymorphonuclear leukocytes surface receptors, the beta 2 integrins, in the interactions of these cells with fibrinogen. We have found that the beta 2 integrins, CD11b/CD18 (complement receptor three) and CD11c/CD18 mediate attachment of polymorphonuclear leukocytes to fibrinogen-coated surfaces. Polymorphonuclear leukocytes must be stimulated with chemoattractants, such as fMLP, or with cytokines, such as tumor necrosis factor to bind to fibrinogen via these integrins. Moreover, each of these integrins interacts with a different segment of the fibrinogen molecule. PMN adherence to fibrinogen via CD11b/CD18 depends on the carboxy terminus of fibrinogen, whereas adherence via CD11c/CD18 depends on the amino terminus of fibrinogen's alpha-chain. One of the physiological consequences of these interactions is that polymorphonuclear leukocytes stimulated with either chemoattractants or TNF form protected compartments at their interface with fibrinogen-coated surfaces and that elastase released into these compartments is inaccessible to protease inhibitors present in the plasma. These protected compartments exclude plasma proteins of > 40,000 daltons such as alpha 1 anti-proteinase, thereby allowing polymorphonuclear leukocyte proteases to degrade matrix proteins within this compartment without interference by plasma anti-proteinases. PMID- 1309033 TI - Platelet-derived growth factor increases plasminogen activator inhibitor-1 activity and mRNA in rat cultured vascular smooth muscle. PMID- 1309034 TI - Plasminogen activator in periodontal health and disease. PMID- 1309035 TI - Effects of cocultivation of human umbilical vein endothelial cells with Bowes melanoma cells. PMID- 1309037 TI - Correlation of in vitro and in vivo decreased fibrinolytic activity caused by dexamethasone. AB - The effect of dexamethasone administration to rats was studied on blood fibrinolytic activity. PAI-1 levels were dose-dependently enhanced by dexamethasone after a pretreatment period of 5 days while simultaneously a decreased tPA level was observed. These ex vivo measured effects were confirmed in vivo with a specially developed fibrinolysis model. It is concluded that the in vivo measured inhibition of the fibrinolytic activity caused by dexamethasone correlates well with ex vivo measured activities. PMID- 1309036 TI - Enhancement of tissue-type plasminogen activator levels by retinoids in rat tissues in vivo. PMID- 1309038 TI - Inhibition of PAF-induced tPA release by KO-286011. PMID- 1309039 TI - Dynamics in thrombus formation. PMID- 1309040 TI - The intrinsic lysis concept. PMID- 1309041 TI - Fibrin, lipoprotein(a), plasmin interactions: a model linking thrombosis and atherogenesis. PMID- 1309042 TI - Thrombin, a link between coagulation activation and fibrinolysis. PMID- 1309043 TI - Regulation of the acute release of tissue-type plasminogen activator from the endothelium by coagulation activation products. PMID- 1309044 TI - Possibilities of intervention in intrinsic and extrinsic lysis programs. PMID- 1309045 TI - The rationale of prevention of thrombosis by enhancing blood levels of single chain urokinase-type plasminogen activator (scuPA). PMID- 1309046 TI - Stimulation of tPA release by mucopolysaccharide polysulfate. PMID- 1309047 TI - Composition and susceptibility to thrombolysis of pathological human arterial thrombi. PMID- 1309048 TI - Cathepsin G, a polymorphonuclear cell protease, affects the fibrinolytic system by releasing PAI-1 from endothelial cells and platelets. PMID- 1309049 TI - Menstruation: extravascular fibrinolytic activity and reduced fibrinolytic capacity. PMID- 1309050 TI - In vitro diagnosis of fibrinolysis: present status and desired improvements. PMID- 1309051 TI - Possibilities and limitations of reaction product analysis. PMID- 1309052 TI - Fibrinogen- and fibrin-degradation products during fibrinolytic therapy. PMID- 1309053 TI - Plasminogen activators and plasminogen activator inhibitors in neural development. PMID- 1309054 TI - Possibilities of DNA analysis for the detection of predisposition to thrombotic disease. PMID- 1309055 TI - Why targeting? Physiological, pharmacological, and economic aspects. PMID- 1309056 TI - Remaining perspectives of mutant and chimeric plasminogen activators. AB - Potential approaches to improve thrombolytic agents comprise the construction of mutants and variants of tissue-type plasminogen activator (tPA) or of single chain urokinase-type plasminogen activator (scuPA, pro-urokinase), of chimeric plasminogen activators and of conjugates of plasminogen activators with monoclonal antibodies. tPA mutants have been constructed with altered pharmacokinetic properties or altered functional properties, including binding to and stimulation by fibrin, resistance to plasmin and to protease inhibitors. Mutants of tPA described to date, obtained by deletion/substitution of functional domains or of single amino acids, have markedly reduced clearances, but usually also reduced specific thrombolytic potencies. Mutants of scuPA with improved thrombolytic potencies have thus far not been reported. Chimeric molecules containing functional domains of both tPA and scuPA have intact enzymatic properties of uPA and some fibrin affinity of tPA. Surprisingly, chimeras endowed with fibrin affinity usually have unaltered or reduced thrombolytic potencies. However, a chimera consisting of amino acids 87-274 of tPA and amino acids 138 411 of scuPA, with negligible fibrin affinity, has a 10-fold higher thrombolytic potency than scuPA in animal models of venous thrombosis, as a result of a delayed in vivo clearance and a relatively maintained specific thrombolytic activity. Plasminogen activators conjugated with antifibrin or antiplatelet monoclonal antibodies, either chemically or by recombinant DNA technology, are targeted to blood clots, resulting in a 5- to 10-fold increased thrombolytic potency. Thus, it is possible to develop plasminogen activators with improved thrombolytic potency. Whether such agents will be clinically useful remains to be established. PMID- 1309057 TI - Antibody targeting as a thrombolytic strategy. PMID- 1309058 TI - Principles underlying the use of conjunctive agents with plasminogen activators. AB - Pharmacological thrombolysis is a dynamic situation in which fibrin degradation occurs concomitant to procoagulant activity. The consequences of enhanced procoagulant and platelet activity may delay or prevent thrombolysis or lead to reocclusive events following successful recanalization. Although heparin and aspirin may attenuate ongoing thrombin and thromboxane generation, respectively, a relatively high percentage (10-20%) of patients treated with heparin and aspirin still have complications associated with thrombolysis. This suggests that heparin and aspirin are not universally effective as the heparin-antithrombin III complex may be inaccessible to fibrin-bound thrombin in the microenvironment of the thrombus and aspirin eliminates only thromboxane-dependent platelet aggregation. Therefore, careful consideration must be given to small molecule, active-site thrombin inhibitors which may prove to be more effective than heparin and to fibrinogen receptor antagonists which block aggregation to all known platelet agonists and have a much broader spectrum of activity than aspirin. Hopefully, well-designed clinical trials will be conducted with safe and effective thrombin inhibitors and/or fibrinogen receptor antagonists in thrombolysis and compared to heparin and aspirin such that potentially the overall efficiency of thrombolysis can be improved upon. PMID- 1309059 TI - Plasminogen activators from the saliva of Desmodus rotundus (common vampire bat): unique fibrin specificity. AB - The saliva of D. rotundus contains at least four plasminogen activators (PAs) which all require fibrin as a cofactor. D. rotundus salivary PAs (DSPAs) exhibit a sequential array of structural motifs such as "Finger" (F), "EGF" (E), "Kringle" (K) and "Protease" (P) which was elucidated by cDNA cloning and sequencing. The respective domain organizations are: FEKP (DSPA alpha 1 and DSPA alpha 2), EKP (DSPA beta) and KP (DSPA gamma). In all four forms the plasmin sensitive site of tPA is obliterated, indicating that they function as single chain enzymes. DSPA alpha 1 differs from alpha 2 by amino acid substitutions found mainly in the F, E and K domain, 11% of the total sequence. DSPA beta and gamma, while being closely related to alpha 2, still exhibit 2 and 13 amino acid exchanges, respectively. These sequence heterogeneities, together with results of Southern blot hybridization experiments, strongly suggest that the four DSPA mRNA species originate from different genes. All four forms of DSPA have been expressed in animal cell culture and DSPA alpha 1 was chosen for a detailed pharmacological characterization. In vitro DSPA alpha 1 activity is enhanced 50,000-fold in the presence of fibrin, whereas the activity of single chain tPA is only enhanced 100-fold. At equally effective thrombolytic doses DSPA causes lower bleeding incidence in a rat mesenteric vein model and exhibits high potency, clot selectivity, and speed in the dissolution of fibrin embolized into the lung of anesthetized rats. In the copper coil-induced dog coronary heart infarction model, at doses that achieve patency at equal rates, reocclusion is significantly less frequent than with tPA. These results indicate that DSPA alpha 1 may be a safer and more efficacious thrombolytic agent than the PAs currently in clinical use. PMID- 1309060 TI - Targeting of thrombolytic agents: current state of knowledge and perspectives. PMID- 1309061 TI - The PA-plasmin system during murine embryogenesis. PMID- 1309062 TI - Bolus application of a novel recombinant plasminogen activator in acute myocardial infarction patients: pharmacokinetics and effects on the hemostatic system. PMID- 1309063 TI - Serum-dependent modulation of the type 1 plasminogen activator inhibitor binding to endothelial cell surfaces. PMID- 1309064 TI - Thrombolytic properties in a rabbit jugular vein thrombosis model of a tissue type plasminogen activator mutant lacking the growth factor- and kringle 1 domains. PMID- 1309065 TI - Recombinant streptokinase for the treatment of thrombotic disorders. PMID- 1309066 TI - Bispecific monoclonal antibodies increase the fibrin-specific fibrinolytic activity of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). PMID- 1309067 TI - Clearance of plasminogen activator--a major determinant of plasma concentration: therapeutic and diagnostic implications. PMID- 1309068 TI - Prolonged coagulation instability is associated with a higher-dose regimen of tissue-type plasminogen activator in patients with acute myocardial infarction. PMID- 1309069 TI - Evidence for a role of factor XII-dependent fibrinolysis in cardiovascular diseases. PMID- 1309070 TI - Immunoelectron microscopic localization of type 1 plasminogen activator inhibitor in the extracellular matrix of transforming growth factor-beta-activated endothelial cells. PMID- 1309071 TI - Effects of retinoic acid on plasminogen activators in murine epidermal cell culture. PMID- 1309072 TI - The mechanism of plasminogen activation and the variability of the fibrin effector during tissue-type plasminogen activator-mediated fibrinolysis. PMID- 1309074 TI - Enhanced activity of plasmin and plasminogen activation in the presence of oleic acid. PMID- 1309073 TI - Modulation of fibrinolysis by thrombospondin. AB - Thrombospondin is a large, trimeric glycoprotein secreted by activated platelets and growing cells. Thrombospondin copolymerizes with fibrin during blood coagulation and deposits in extracellular matrix. We found that thrombospondin is a slow (rate constant approximately 6.3 x 10(3) M-1 sec-1), tight-binding (Kd < 10(-9) M) inhibitor of plasmin as determined by loss of amidolytic activity, loss of ability to degrade fibrinogen, and decreased lysis zones in fibrin plate assays (Biochemistry 31: 265-269, 1992). Thrombospondin also slowly inhibits urokinase plasminogen activator. The lysis zone when urokinase is put on fibrin plates made from whole plasma is less if thrombospondin is present. The stoichiometry of inhibition is approximately one mole plasmin:one mole thrombospondin trimer, a somewhat surprising result considering the trimeric nature of thrombospondin. These results indicate that thrombospondin is an important regulator of fibrinolysis and degradation of extracellular matrix, particularly when these processes are initiated by urokinase and even when other inhibitors of fibrinolysis are present. PMID- 1309075 TI - Plasminogen activators and their inhibitors in arthritic disease. PMID- 1309076 TI - Progress and problems of interhospital consulting by computer networking. PMID- 1309077 TI - Networking the health community of New York State. PMID- 1309079 TI - IEEE P1157 MEDIX: a standard for open systems medical data interchange. PMID- 1309078 TI - The general medical record. Concepts and suggestions for implementation. AB - Our view of a general medical record consists of a combination of distinct departmental- and specialty-specific medical records and an organizing kernel that contains arguably critical information. Because this system allows each clinical entity to evolve its own system, clinical priorities do not have to be negotiated or compromised. Additionally, subsystem or departmental medical records can be easily revised without disturbing the general medical record because of the modular design. Although the system seems robust with respect to design considerations, only implementation can provide adequate tests. PMID- 1309080 TI - Medicine in the Matrix. PMID- 1309081 TI - DecisionNET: database/network support for clinical decision analysts. AB - DecisionNET is a proposed remote database/wide-area computer network that should cultivate quantitative approaches to medicine by providing rapid access to medical facts, literature citations, decision models, and commentary of specific use to those involved with quantitative clinical decision making. Increasing accessibility to data and providing a forum for exchange of ideas should prove to be a significant asset to clinicians, either as modelers or as clients. Further work will address specific database implementation, development of a query engine, and coordination of the communications infrastructure. DecisionNET provides a unique model for the growth and maintenance of other medical knowledge bases. PMID- 1309082 TI - Clinical data retrieval and analysis. I've seen a case like that before. PMID- 1309084 TI - Expert systems, clinical data analyses, and knowledge discovery: the POSCH AI project. PMID- 1309083 TI - Improved care of patients with diabetes through telecommunications. AB - This project tested the importance of enhanced information transfer of home monitoring results to health care providers. The study tested whether computer assisted communication of medical information between the chronic care patient and the physician can result in health care benefit. The information tools were constructed/adapted as a test of this hypothesis for diabetes mellitus. Patients connected a glucometer to an intelligent modem weekly for six to nine months. Graphical and mathematical tools extracted and emphasized the information content of the home monitoring data arriving at the central site. Data smoothing, trend analysis, and calculation of quality control statistics were incorporated into a graphical time series oriented report that was used by the health care provider during an outpatient visit. The integrated home monitoring system was tested on 20 patients with diabetes in a double cross-over design over a 15-month period. A significant improvement in serum glucose control as measured by glycated hemoglobin was shown in the study group, but not in the control group. PMID- 1309085 TI - Medical Information Service via Telephone. The pioneer of physician consultation services. AB - The organization and development of MIST were a response to the needs of health professionals in Alabama, principally rural physicians, who expressed a desire to access the knowledge of the faculty at the UAB Medical Center. MIST provides free service on a 24-hour, 7-day-a-week basis for physicians around the world. At any time, practitioners can obtain specific medical information and discuss possible diagnoses or patient-related problems with UAB specialists. MIST, the first and largest medical professional telephone consultation program of its kind, receives numerous requests from other institutions seeking information and advice on developing similar programs. Such programs now exist in many states. One reason for the success of MIST is that it has always enjoyed high visibility with UAB physicians, credibility with the physician callers, and priority within UAB's Office of the Vice President for Health Affairs. As a consultative system, MIST continues to contribute to improved health care for citizens of Alabama and beyond and to save patients and taxpayers the expense of unnecessary or inappropriate treatment. MIST provides consultation and continuing education at the moment of need for the professional in private practice. In return, UAB specialists are given access to vital research and demographic information, as well as patient referrals. MIST plays an important role in removing barriers to education and consultation for busy medical personnel and in facilitating patient referrals to an acclaimed center of research and excellent patient care. Rather than searching for the proper contact, one call to an easy-to-remember number puts the health professional in touch with the appropriate source. Rural doctors, as well as medical personnel working in urban areas, can feel that they are practicing "right next door" to an outstanding university medical center where colleagues who are ready and able to offer expert consultation and support at the critical moment of need are only a telephone call away. PMID- 1309086 TI - West Virginia CONSULT: enhanced information access for health care practitioners in a rural environment. PMID- 1309087 TI - GaIN: on-line delivery of medical information to physicians and hospitals in Georgia. PMID- 1309088 TI - The selected impacts of electronic and computer technologies on law. PMID- 1309089 TI - An overview of networking for physicians and problems of network consulting in remote areas. AB - For computer networking the most suitable operating systems are UNIX or MS-DOS. As networking software UUCP and TCP/IP are most common. Hardware requirements are derived from the operating system and from the networking software. Low-cost solutions, for example, uuPC, a public domain version of UUCP, require only an 8088 processor and a 2400-baud modem. TCP/IP fares better with more powerful processors and requires permanent lines between the connecting computers. In developing countries the introduction of computer networks is hampered by several factors: lack of foreign exchange, price of hardware and software, unreliable electricity and telephone lines, lack of hardware and software support, large distances to the nearest center, and incompatibilities between existing systems and the network. Important aspects for clinical networking in developing countries include appointment scheduling in the referral hospitals, access to laboratory and pathology results from the central laboratory, and primary health care information such as epidemiologic data. Advanced systems, for example, for image processing, are not yet feasible in developing countries. PMID- 1309090 TI - Protecting the privacy of patient information in clinical networks: regulatory effectiveness analysis. AB - Patient privacy is one of the major issues in the development of modern clinical information system networks. Such networks will have to demonstrate an appropriate concern for privacy as a precondition of operation. Regulatory effectiveness analysis is a novel technique for measuring compliance with a technological regulatory system. By examining the public policies, legal structures, and technical tools involved in the regulatory system, it is possible to discover discontinuities that may result in noncompliance with the regulatory system. PMID- 1309091 TI - The use of wide area computer networks in disaster management and the implications for hospital/medical networks. AB - Computer-mediated communication in various forms is already being used in all phases of disaster management--preparation, response, recovery, and long-term mitigation. However, to date wide area computer networks--particularly the Internet (the supernetwork of networks)--have been used only to a limited extent in disaster management and prevention. Some of these applications are described in this paper. Nevertheless, the high speed and ease of information transfer by computer network and the vast resources becoming available on the Internet make it inevitable that the use of computer networks to temper disasters will increase enormously in the next decade. The Internet will provide a key means through which networks initially dedicated to solely medical purposes and the individuals who use them will become involved not only in disaster response and mitigation worldwide, but in the global community and consciousness that is the Internet. PMID- 1309092 TI - Staff communications and credentialing in a multisite institution. PMID- 1309093 TI - Some tools for the diffusion of biomedical information using research networks. AB - Research and academic computer networks provide e-mail and other services to all members of participating institutions. Their usage by biomedical researchers and clinicians is still limited because of several reasons, including limited awareness of the available network resources. An increased use of these networks within the biomedical community would allow fast, effective communications and convenient remote access to information sources. As an example and pilot study, we prepared two network tools to make some information services maintained by our institution also accessible through e-mail. Both tools were implemented using PMDF e-mail software on a DEC MicroVAX connected to the Italian academic and research network (GARR), which is linked to the U.S. Internet. A network server takes care of automatic distribution of documents (files) reporting results of an oncology research/education project. An information server provides for semiautomated support of a consulting service on use of drugs. The feasibility of implementing these tools, based on existing software, further illustrates the potential usefulness of research computer networks for the dissemination of biomedical information. PMID- 1309094 TI - The saving of Oleg. A USA-USSR medical success using packet and ham radio, facsimile, and electronic mail. PMID- 1309095 TI - Medical education and decision support using network-based multimedia information resources. PMID- 1309096 TI - Multimedia communications in health care. PMID- 1309098 TI - Teleradiology for consultation between practitioners and radiologists. PMID- 1309097 TI - Expediting prior approval and containing third-party costs for dental care. AB - Dental insurance carriers frequently require referral of radiographs for determination of prior approval. Radiographs are also often used for obtaining expert opinions before finalizing diagnoses and establishing treatment plans. Traditionally, such referrals have been carried out using the original or duplicate films transmitted through the postal system. Studies concerning alternative communication media for data transmission are presented, namely, the use of switched-digital telephone lines and of electronic mail networks. PMID- 1309099 TI - Nephropathology consultation via digitized images. AB - Investigations into a digitized image communications system were prompted by a need to bring expert consultation to physicians in community practice. Pathologists desired the capability to concomitantly view, annotate, and discuss images with referring physicians at distant sites. Methods included evaluation of the human and procedural domain into which the system was to be integrated. The GDCN computer consultation system has the consultant nephropathologist first evaluate the processed biopsy slides, digitize representative images, transmit them with the diagnosis to referring nephrologist, and, finally, conduct an interactive consultation and review of the biopsy and case. Image resolution and compression variables must be set for each individual medical consulting application. For the GDCN, it was found that the 640 x 496 x unlimited color with compression ratios not exceeding 1:32 are acceptable. An obvious improvement of this computerized system over the noncomputerized review sessions is the ability to immediately share and discuss a new image that had not been previously sent. In the old noncomputerized consultation, only images that had been mailed could be discussed. The computerized sessions allow transmission (10 sec) of a new image that the consultation might demand. The computerized sessions also provide the ability to show the referring nephrologist an area of biopsy interest that the pathologist had not previously transmitted. Biopsy slides can be viewed during the consultation, an area digitized, and that image transmitted to the nephrologist during the consultation. Hardware and costs for the sending station were: [table: see text] This system far exceeds the requirements for this particular application; however, it is sufficient to support future, higher technology computer applications. If necessary, this same system could be used with a less expensive computer, a less expensive camera, software compression, and a single monitor. These alterations could lessen the expenditures by some $8000 and result in a total cost of $10,000. Hardware and costs for the receiving station were: [table: see text] Cost of the receiving station could be reduced by using a less expensive computer and a single monitor system, thereby saving up to $5000 and resulting in a total cost of $7,400. DCCEC and GDCN have elected to use the more expensive, user-friendly and more rapid image transmission system SEND- >IT, rather than the less expensive system mainly because of experience with incorporating the system into the daily activities of the GDCN. SEND-->IT best met the essentials for GDCN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309101 TI - Teleradiology for the emergency room. PMID- 1309100 TI - The French Communicable Diseases Computer Network. A seven-year experiment. PMID- 1309102 TI - Babinski's bulletin board system. A computerized message BBS for neurologists. PMID- 1309103 TI - Medical and clinical chemistry networks and bulletin boards in Argentina. PMID- 1309104 TI - Computer communication for international collaboration in education in public health. The TEMPUS Consortium for a New Public Health in Hungary. AB - Computer conferencing using the Canadian system CoSy is presented, and three related projects are discussed. 1. An extramural university course in epidemiology and medical statistics was taught using CoSy. Computer conferencing can be a useful vehicle for distance education, enabling health professionals to attend "classes" independent of geographical and time constraints. The subjects taught are well suited to this medium. 2. Internet was used to establish a small network of public health researchers and teachers. Participants are from Canada, Hungary, Israel, Norway, and Australia. Networks of this type not only facilitate international collaboration within public health, they also enable international collaborative research and teaching projects that would have been too cumbersome and time consuming to initiate and conduct without this communication facility. 3. "Development of Medical Education for a New Public Health in Hungary," a project funded by the European Community's TEMPUS program, is established with a view to developing the undergraduate and graduate education of public health professionals. It is a joint program between the five Hungarian medical schools and ten universities in the G24 countries. The TEMPUS listserver functions as an important vehicle for communication within this project. PMID- 1309105 TI - Exchange of Veterans Affairs medical data using national and local networks. AB - Remote data exchange is extremely useful to a number of medical applications. It requires an infrastructure including systems, network and software tools. With such an infrastructure, existing local applications can be extended to serve national needs. There are many approaches to providing remote data exchange. Selection of an approach for an application requires balancing of various factors, including the need for rapid interactive access to data and ad hoc queries, the adequacy of access to predefined data sets, the need for an integrated view of the data, the ability to provide adequate security protection, the amount of data required, and the time frame in which data is required. The applications described here demonstrate new ways that the VA is reaping benefits from its infrastructure and its compatible integrated hospital information systems located at its facilities. The needs that have been met are also needs of private hospitals. However, in many cases the infrastructure to allow data exchange is not present. The VA's experiences may serve to establish the benefits that can be obtained by all hospitals. PMID- 1309106 TI - Telecommunications in rural America. Opportunities and challenges for the health care system. PMID- 1309107 TI - Innovative desktop learning tools. Implications for rural hospitals and physicians. AB - Innovative methods of providing workplace education for health care professionals may be a key to the survival of rural hospitals in America. Such methods must overcome time, distance, cost and organizational constraints, and take into account the structure of the learning experience. The Texas Hospital Education and Research Foundation has recently been involved in two programs that tested new approaches to worker education using distance-learning strategies. The projects--resource sharing among rural directors of nursing and training for cancer tumor registrars--used computer-conferencing technology. A new model using existing satellite, audio-conferencing, and computer-based instruction augmented by computer conferencing is proposed. The Computer-Related Assisted Distance Learning Enhancement (CRADLE) model integrates existing technologies to provide education to health care workers at their desktop. The Cancer Learning Center (CLC) tested peer collaboration, the primary component of the model. The ultimate goal is to have the system available to all tumor registrars in Texas, and to secure funding to implement rural nursing and rural high-school health occupations education projects. Current projects from set-up through results are presented. PMID- 1309108 TI - The Synapse health information network. Linking Nebraska and the midwest. PMID- 1309110 TI - Assisted reproduction. PMID- 1309109 TI - Where do we go from here--is there a future for assisted reproductive techniques? PMID- 1309111 TI - Oogenesis, fertilisation and early embryonic development in rats. I: Dose dependent effects of pregnant mare serum gonadotrophins. AB - Five hundred and eight mature female Wistar rats divided into 35 different groups were stimulated with pregnant mare serum gonadotrophins (PMSG) (0, 5, 10, 20 & 40 IU) at the late diestrus stage to induce multiple follicular development. No chorionic gonadotrophin (CG) was used for ovulation induction. The quality of oocytes and their in vitro fertilisability, quality of Day 2-embryos, viability of pregnancy and status of fetuses on Day 14 of gestation and status of embryos retrieved on Day 2, 3, 4 and 5 of pregnancy in different subgroups of rats were examined. Results showed that more oocytes and embryos fertilised in in vivo were retrieved from rats supraphysiologically stimulated with 20 IU of PMSG. However, concurrent with the larger number, higher proportions of abnormal oocytes and embryos were found. High doses of PMSG caused lower in vitro fertilisability of oocytes and greater degrees of embryonic degeneration. Although, the number of oocytes and Day 2-embryos were higher in the 20PMGS dose group, the pregnancy rate was significantly reduced to 27%. In the 40PMSG group no viable pregnancy was noted. Most embryo demise occurred by day 3-5 of pregnancy, probably within the oviducts and before the implantation stage. In rats supraphysiologically stimulated with 20 and 40 IU of PMSG, the number of morphologically normal looking embryos was greatly reduced by Day 3-5 of pregnancy. In the 40PMSG group, there were no embryos retrieved by Day 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309112 TI - Oogenesis, fertilisation and early embryonic development in rats. II: Dose dependent effects of human chorionic gonadotrophin. AB - A total of 950 female Wistar rats in 81 groups were involved in this study. Different groups of rats were stimulated with PMSG (0, 10 & 20 IU) at diestrus followed, 48-52 hr later, by different doses of HCG (0, 10, 20, 30 & 40) for ovulation induction. The dose-dependent effects of HCG, either with or without the use of PMSG for stimulation of multiple follicular development, on the quality of oocytes and their in vitro fertilisability, quality of Day 2-embryos, viability of pregnancy and status of embryos retrieved on Day 2, 3, 4 or 5 of pregnancy in different subgroups of rats were examined. Results showed that more oocytes and embryos fertilised in vivo were retrieved from rats supraphysiologically stimulated with 20 IU of PMSG. The addition of HCG did not increase the number of ovulated oocytes or Day-2 embryos. In other words, the number of oocytes or embryos produced is dependent on the dose of PMSG administered during diestrus rather than on the dose of HCG given for ovulation induction. Hence, no increase in the amount of HCG is required to effectively ovulate bigger cohort of preovulatory follicles in supraphysiologically stimulated rats. As was shown earlier, in vitro and in vivo fertilisation rates were reduced when higher doses of PMSG were used. Similarly, these rates were reduced when increasing doses of HCG were used in rats not previously stimulated with PMSG. When higher doses of HCG were used in rats stimulated earlier with PMSG (10 and 20 IU), the in vitro but not the in vivo fertilisation rates were further reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309113 TI - Indications for in vitro fertilisation: changing trends: the Norfolk experience. AB - From January 1987 to December 1990, 1,415 patients were enrolled for in vitro fertilisation (IVF), series 26-41, at the Jones Institute for Reproductive Medicine. They underwent 2,393 IVF cycles. The most common indications were tubal factor (57.3%), male infertility (22.0%), endometriosis (10.9%), and idiopathic infertility (5.2%). This represented a significant decrease in the proportion of cycles performed for tubal disease and an increase in the proportion of cycles performed for male infertility as compared with the earlier series 1-16, 1981 1984. Total pregnancy rates from fresh transfers remained stable for most indications, being the lowest for diethylstilbestrol (DES) exposure (16.7%), and highest for immunologic infertility (47.6%). In addition, patients with polycystic ovarian disease (PCOD) had a high pregnancy rate (47.2%) from fresh transfers but a high first trimester abortion rate as well (19.4%). The ongoing pregnancy rate from fresh transfers for the whole population was around 19.0%, being highest for patients with immunologic infertility (31.8%) and lowest for DES exposed patients (9.3%). The cumulative ongoing pregnancy rate to date for the whole population from fresh and cryopreserved embryos was 21.6% per embryo transfer (range from 13.3% for DES patients to 33.3% for immunologic infertility). The projected ongoing pregnancy rate as obtained from adding the number of cumulative pregnancies to date to the number of predicted ongoing pregnancies calculated from the remaining frozen embryos was 23.9% for the whole population (range 16.7% for DES patients to 33.3% for immunologic infertility).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309114 TI - Outcome of cryopreservation and subsequent programmed replacement of frozen thawed embryos in an in vitro fertilisation programme: preliminary report and proposals for improvement. AB - In order to prevent wastage of good quality embryos and limit the number transferred in fresh in vitro fertilisation (IVF) cycles, 577 supernumerary embryos were cryopreserved for a mean duration of 6.23 +/- 4.7 months (range 1 24). Four hundred and twenty-two have been thawed so far of which 81 (19.19%) were totally lysed, 317 (75.12%) survived with at least 50% of their blastomeres intact and 180 (42.65%) cleaved. Two hundred and sixteen frozen-thawed embryos have been transferred in 62 stimulated and 11 natural cycles involving 61 patients. The mean number of embryos transferred per cycle was 2.96 +/- 0.86. Twenty-one pregnancies resulted from the 62 stimulated cycles (33.87%). No pregnancy occurred in the 11 natural cycles. Overall pregnancy rate was therefore 28.77%. Eleven singletons (eight male; three female) and one set of twins (one male one female) have so far been delivered in good condition:- six (54.5%) by caesarean section, five (45.5%) vaginally, including one by Neville Barnes forceps, one ventouse and the rest were spontaneous. Presentation was cephalic in 10 (91%) and breech in one case (9%). All were delivered at term except one premature (9%). Mean birth weight was 3.23 +/- 0.32 kg for singletons and 2.7 kg for the twins. Despite the diversity of racial, cultural and religious differences in our multinational patient population, we found embryo cryopreservation following IVF generally acceptable and our preliminary results are quite encouraging. Strategies for improving the outcome of future cycles are proposed. PMID- 1309115 TI - The spontaneous LH surge in ovarian hyperstimulation for assisted reproductive technology. AB - Thirty-seven patients who underwent assisted reproductive technology programme, in vitro fertilisation or embryo transfer and gamete intra-fallopian transfer, were randomised into two groups in order to evaluate frequency of premature spontaneous LH surge when stimulated with different type of hMG. An hMG (FSH:LH = 1:1) was administered for eighteen patients (group A) and the different highly purified hMG (FSH:LH = 19:1) was administered for nineteen patients (group B). Blood samples are drawn from day 3 of the cycle until hCG administration, and serum LH level are measured in the frozen samples. There were no statistical difference in the total amount of hMG used before hCG injection, days of hMG injection and the number of oocytes retrieved between two groups. The premature spontaneous LH surge occurred only one patient in group A (5.6%), but more frequent LH surge was observed in group B (42.1%) (p < 0.05). It is suggested that the different FSH/LH ratio may be the reason for the difference of the incidence of premature spontaneous LH surge. PMID- 1309116 TI - Human preimplantation development in vivo: ultrastructural observations. AB - The ultrastructure of a 2-cell, 4-cell, 7-cell and 16-cell human embryos fertilised and developed in vivo were compared using transmission electron microscopy. Among the structures which exhibited more notable changes throughout these developmental stages, were the mitochondria, ribosomes, nuclear envelope and nucleolus. Mitochondria which were initially round, dense with cristae oriented parallel to the surface changed to oval with less dense mitochondrial matrix and with cristae perpendicular to the mitochondrial membrane. Ribosomes and polyribosomes decreased in amount from 2 to 7-cell stages and increased again at the 16-cell stage. The nuclear envelope exhibited intense blebbing activity at the 4-cell stage, less at 7 and none at 16. The nucleolus initially very dense was progressively infiltrated by chromatin, became reticular at the 7-cell stage and appeared fully mature at the 16-cell stage. This study discloses structural details of human preimplantation embryos which may be of interest in the assessment of comparable material obtained in vitro. Some unique features that may have bearing on the ontogenesis of cell organelles and cell differentiation are discussed. PMID- 1309117 TI - In vitro fertilisation in capillary tubes for male factor infertility. AB - In 26 patients with severe factor infertility (total spermatozoa per ejaculate 0.8-6.3 million) in vitro fertilisation was performed using a capillary tube culture system. Spermatozoa were concentrated and incubated with oocytes in a very small volume (10-20 microliters) within capillary tubes. In seven out of 26 patients (27%) at least one oocyte could be successfully fertilised (overall fertilisation rate 11.6%, 22/190 oocytes) and in two patients a pregnancy with the birth of a healthy child could be observed. If sperm progression was only of grade 2 or less no fertilisation could be observed in 10 patients with a total of 75 oocytes. The described capillary technique for in vitro fertilisation using very small volumes for sperm-oocyte culture may be useful in cases of severe oligozoospermia or before considering extreme therapies such as donor insemination of sperm microinjection. PMID- 1309118 TI - Oocyte maturation in human in vitro fertilisation programmes. AB - Oocyte immaturity represents a serious loss of efficiency in the in vitro fertilisation (IVF) treatment cycle since it is associated with a great list of detrimental effects mainly reflected in lower fertilisation and pregnancy rates. In stimulated cycles, oocyte maturation depends on stimulation protocol, ovarian response, time of human chorionic gonadotrophin (hCG) administration, hCG to oocyte retrieval interval, and/or time of in vitro culture period before insemination. The present review discusses the influence of these factors on human oocyte maturation and proposes several preventive and corrective measures. Due to the difficulty of ascertaining the grade of oocyte maturity based on morphological and physical properties of the oocyte-corona-cumulus complex (OCCC), fertilisation rate has been considered as an indirect index of nuclear and cytoplasmic maturation. The proportion of immature oocytes increases as the ovarian response to gonadotrophins increases. However, the detrimental effects of oocyte immaturity in high responders may be balanced by the higher number of oocytes retrieved per patient (and available embryos for transfer) and the selection of the best embryos for transfer. Oocyte immaturity might be prevented by delaying hCG injection and/or oocyte retrieval. Corrective strategies would involve in vitro or in vivo culture before insemination; addition of gonadotrophins or epidermal growth factor to the culture medium; and coculture with granulosa cells. PMID- 1309119 TI - Oocyte maturation and its clinical significance in assisted reproductive technology. AB - The characteristics and regulation of oocyte maturation in the normal menstrual cycle is reviewed and the mechanisms by which ovarian hyperstimulation with exogenous gonadotrophins, used in assisted reproductive techniques, can disturb this process, is discussed. It is postulated that derangements induced in the maturation of oocytes in the hyperstimulated cycle result in the recovery of poor quality oocytes at egg-pickup which have a reduced potential to undergo normal fertilisation and subsequent embryonic development. PMID- 1309120 TI - The use of luteinising hormone releasing hormone agonists for ovarian stimulation in assisted reproductive technology. AB - Although the use of luteinising hormone releasing hormone (LHRH) agonists and human menopausal gonadotrophin (hMG) for ovarian stimulation in assisted reproductive technology has gained wide-spread popularity, a number of major issues regarding their use remain unresolved. In this paper, we examine some of these issues in the light of the results of our own studies. We have found that although the use of LHRH agonists may be advantageous for some patients, its routine use for all patients produces no significant medical advantage compared with conventional stimulation regimens. In a number of prospective randomised studies, we have found that the long protocol of LHRH agonist administration is superior to the short and ultrashort protocols and the administration of glucocorticoids to patients at high risk of developing ovarian hyperstimulation syndrome does not reduce the incidence of this complication. Finally, we have found that when the long protocol of LHRH agonist administration is used, precise timing of human chorionic gonadotrophin administration (hCG) is not important. There are no significant differences in oocyte recovery, fertilisation and cleavage rates, or in pregnancy rates when the results of standard timing of hCG administration are compared with delayed administration. It would, therefore, appear that the major advantage of the routine use of LHRH agonists is for practical, rather than medical reasons. PMID- 1309121 TI - Methods of sperm preparation for assisted reproduction. AB - Because seminal plasma contains factors which inhibit the fertilising ability of spermatozoa, it is essential that spermatozoa be separated from it quickly and efficiently. Four basic approaches for this exist: (1) simple dilution and washing; (2) sperm migration (either direct from liquefied semen, from a suspension of washed spermatozoa or from a washed sperm pellet); (3) selective washing procedures (mainly Percoll and Nycodenz density gradients); and (4) adherence methods for the elimination of debris and dead spermatozoa (glass wool, glass beads and Sephadex columns). While the success of a sperm preparation method is often assessed by its yield of motile spermatozoa, it is also vital that sperm preparations for clinical use should be free of any microbiological contaminants present in semen. Other relevant considerations in choosing a method include its technical complexity as well as its material, apparatus and time costs. Any possible exposure of spermatozoa during preparation to deleterious influences that may cause iatrogenic sperm dysfunction must obviously be avoided at all costs. Consequently, methods involving centrifugal washing steps prior to the selection of motile spermatozoa should be discontinued. Direct swim-up from semen remains the simplest way to obtain populations of highly motile spermatozoa and, dependent upon the absolute yield required, can be a very rapid procedure with normal semen samples. Abnormal samples, especially those with increased viscosity, may benefit from a prior filtration on a glass bead or Sephadex column. The initial motile sperm preparation should be washed once (perhaps twice) to minimise seminal plasma contamination of the final preparation. Several rapid, simple discontinuous Percoll gradients giving excellent yields are available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309122 TI - In vitro fertilisation in immunological infertility. AB - Fertilisation occurs through a complex and orderly sequence of changes in both the oocyte and the spermatozoon. Although mechanisms have evolved to protect spermatozoa from recognition by the immune system, there is evidence that a breakdown in protection can occur resulting in homologous or heterologous antisperm antibodies which can immobilise or agglutinate spermatozoa leading to infertility. Antisperm antibodies may affect the reproductive process by interfering with sperm survival and motility and sperm transport through cervical mucus. Fertilisation is also affected, and those oocytes that do fertilise go on to develop poorly. Antisperm antibodies appear to inhibit sperm attachment to and penetration of the zona pellucida. Immune recognition of sperm antigens, which are normally present on the surface of the embryo once fertilisation has occurred, may lead to abortion after implantation. Despite the adverse effects of antisperm antibodies on fertilisation and embryo development, acceptable pregnancy rates can be achieved with assisted reproductive techniques using sperm washing to remove antibody and using a protein source other than female serum. Further study is necessary to understand the mechanism of immunological infertility and to evaluate newer techniques using micromanipulation of gametes to achieve fertilisation. PMID- 1309124 TI - Cytogenetic analysis of oocytes and embryos. AB - Abnormal embryo development represents the major cause of implantation failures and accounts for the low rate of human infertility in vivo or in vitro. Chromosome abnormalities are widely involved in this process. Indeed, 28.4% of oocytes carry a chromosome aberration, i.e. 25.6% aneuploidy and 2.8% structural anomalies. Fertilisation abnormalities (possibly increased by in vitro procedures) were recorded: 7 to 28% of oocytes from fertilisation failure showed a sperm premature chromosome condensation probably resulting from ooplasmic immaturity. Moreover, 1.6% and 3.8% of inseminated oocytes had either a single or 3 pronuclei demonstrating parthenogenesis or triploidy, respectively. In vitro developmental capacities of embryos depends on the degree of ploidy. Parthenogenetic embryos display a fairly normal development until implantation. Triploid zygotes show an original way of division: half of them divide first into 3 cells and then into 6 cells (via a tripolar spindle) whereas diploid zygotes divide into 2 and then 4 cells. As a consequence of either meiotic or mitotic non disjunctions or fertilisation anomalies, 25 to 71% preimplantation embryos carry a chromosome disorder. As an outgrowth of in vitro fertilisation and embryo transfer, detection of genetic and metabolic defects prior to implantation might be possible in the future. So far, 6 girls have been born in couples at risk of transmitting X-linked disease. This technic will increase the efficiency of IVF and avoid the trauma of repeated abortions. PMID- 1309123 TI - Epididymal sperm in assisted reproductive technology. AB - Infertile men with obstructive azoospermia mainly due to congenital absence of the vas deferens (CAVD) now have the option of trying to father their own progeny. In fact, in the last five years epididymal sperm retrieval microsurgically have been successfully used for in vitro fertilisation of human oocytes. In this report the clinical results of 98 consecutive procedures of microsurgical epididymal sperm aspiration (MESA) combined with in vitro fertilisation (IVF) and tubal embryo transfer (TET) are described. An overall fertilisation rate of 17% and a pregnancy rate of 36% per transfer is reported. Five of the 18 pregnancies resulted in abortion (27%) and 13 were delivered at term. Additionally, extra embryos for freezing and potential use for future attempts were made available for 13 couples. Men with CAVD have also allowed the study of spermatogenesis, immunological response and sperm disposal mechanisms in condition of chronic obstruction. PMID- 1309125 TI - Oocyte and embryo donation. AB - Oocyte and embryo donation, first reported in humans in 1983 has helped patients who do not possess functional ovarian tissues or whose oocyte cannot be used for fertilisation, to conceive. Though it is the female counterpart as the donor insemination in the male, it imposes quite different bioethical issues. The article is a review of the oocyte and embryo donation programme in general, with special discussion on regimes of Cyclic Steroid Replacement Therapy, the recruitment of oocyte donors, bioethical issues, and future applications of oocyte donation in medicine. PMID- 1309126 TI - Micro-insemination sperm transfer (MIST) and its application to male subfertility: current strategies to improve results. AB - It can be difficult to achieve a pregnancy for patients with severe male factor subfertility. Hence, micro-manipulation techniques, have been applied to this problem. Direct deposition of sperm into the oocyte under the zona (micro insemination sperm transfer, MIST) has improved the fertilisation rates, but pregnancy rates have been very low. This paper describes the possible new strategies to improve the technique currently. They include methods to improve sperm recovery, to improve acrosome reaction, to improve the quality of embryos by using co-cultures and to wait for good cleavage before transfer, and to improve luteal phase support. There are also many new techniques being developed which may contribute to further pregnancy successes. They include the use of electro-fusion, laser-fusion and the Xenopus cell-free system. PMID- 1309127 TI - Selective assisted hatching of human embryos. AB - Overall results of assisted hatching by zona drilling using acidic Tyrode's solution performed during three randomised trials in 330 in vitro fertilisation (IVF) patients are presented. It was demonstrated retrospectively and prospectively that assisted hatching by zona drilling was effective in embryos with thick zonae (> 15 microns). This procedure is called selective assisted hatching. In order to investigate whether the success rate of embryos with thin zonae (< 13 microns) can be improved further, a fourth trial was executed in 40 consenting patients. Embryos with thin zonae were left intact in one group (control), while the outside of zonae of similar embryos were thinned with acidic Tyrode's solution. Results thus far indicate that embryos with thin zonae do not benefit from this technique. Embryonic implantation (fetal heartbeat per embryo) was high (26%-27%) in both arms of the trial, probably as a result of selective zona drilling of low prognosis embryos with thick zonae. A method is presented for quantifying zona hardening in human embryos. The exposure to acidic Tyrode's solution of each embryo was expressed as a function of the duration to pierce the zona and the diameter of the needle. Preliminary findings suggested that embryonic viability is correlated with zona hardening. In order to test the hypothesis that extracellular fragments may affect embryonic viability, small amounts of fragments were removed from embryos during assisted hatching. The pregnancy rate in 36 patients with extracted fragments was relatively high (41%) considering the poor morphology of the embryos involved. PMID- 1309128 TI - Human ampullary co-cultures for blastocyst transfer in assisted reproduction. AB - Although the assisted reproductive techniques (ART) have contributed significantly over the last decade in alleviating subfertility in the childless couple, the implantation and take-home baby rates have been stubbornly low. A major cause for such low success rates has been the reduced viability of replaced embryos perhaps induced by the suboptimal in vitro conditions used in ART laboratories. One approach to improving embryo viability is to provide the growing embryo with a simulated in vivo environment by replicating the conditions existing in the human fallopian tube in vitro. This requires either the maintenance of an intact fallopian tube in vitro or establishment and maintenance of tubal epithelial cell-lines which could be used as feeder layers for early embryonic growth. The concomitant growth of cells with embryos in vitro has been referred to as co-culture. This paper discusses the in vitro behaviour of human tubal epithelial cells, the fertilisation and growth of embryos in ampullary co culture, the specificity of co-cultures, the mechanism of action of co-cultures and the methods of screening the human ampullary co-culture system for microbes. The pregnancy and implantation results on 50 patients enrolled for a co-culture clinical trial are presented and the future use of this system discussed. PMID- 1309129 TI - Understanding the fundamentals of embryology in assisted reproductive technology. AB - This paper emphasises the need to understand the fundamentals of embryology in relation to in vitro fertilisation (IVF) and associated assisted reproductive technologies (ART). It introduces the reproductive technologist and others involved in such programmes to the events that occur during early embryogenesis, which have led to recent developments in IVF/ART. It also covers some of the contributions made by IVF/ART in understanding early events of development, particularly during the first week of human life. The reader is referred to some of the widely used embryology texts and audio-visual aids and also to selected reviews and papers published recently that would help toward a better understanding of early development and ART. PMID- 1309130 TI - Ethical issues in assisted reproduction. AB - Since the birth of Louise Brown in 1978, no other area in clinical practice and medical research has held the public interest to the same extent as the assisted reproductive technologies. This has led to the formation of committees of enquiry, guidelines from professional bodies, the passage of legislation, and the formation of legislative bodies. The ethical issues which arise in the clinical practice of assisted reproduction, the donation of gametes and embryos, and their cryopreservation, surrogacy, and human embryo research are reviewed. PMID- 1309131 TI - Duodenal pseudomelanosis. PMID- 1309132 TI - [Post-streptococcal immunity in the child in acute articular rheumatism (R.A.A.) or recurrent sore throats]. AB - It concerns comparative studies between two children groups: One group who had previous RAA. A second group who had anginas only. This work shows the interest to associate two streptococcal serologic tests (ASLO, ASD) in order to increase the number of recent diagnostic streptococcal infectious. The remaining immunity is missing in children less than 5 years old; more than 50% of above 10 years an antistreptococcal answer although they have not streptococcus infections presently. PMID- 1309133 TI - [Prospective study of Listeria in humans and animals]. AB - During 1967 to 1985, three cases of listeriosis were reported in Algeria; at that time Listeria monocytogenes caused several thousand cases of meningitis and sepsis in the world. In order to determine the frequency and bacteriologic characteristics of strain isolated in Algeria, a prospective investigation was carried from 1985 to 1989 in humans and animals samples. Sensitivity tests to antibiotics (MIC) point out that all isolates strains are resistant to cephalosporins (first and third generation), but are susceptible to Ampicillin and Gentamicin which ought to constitute the treatment basis of listeriosis. PMID- 1309134 TI - [Listeria serotyping]. AB - Serotyping of Listeria has contributed to bring to light on the origin of outbreaks listeriosis; on the other hand, it is also an additional expression for the identification of Listeria genus. In order to get better in this field, we have produced five factors sera: I, I/II, V/VI, VI, VII. PMID- 1309135 TI - [Preliminary epidemiological study of carriers of Clostridium difficile]. AB - 171 samples have been taken from stools of sick persons in three departments of university and hospital centres of Algiers (C.H.U.A.): the department of maternity (C.H.U Parnet), the department of breast diseases (CPMC), the department of women's surgery (CPMC), 13 samples of C. difficile have been isolated with a frequency of 7.6 per 100 of cases. The rate of conveyance seems more important in adults in hospitals and often concerns sick persons enduring digestive cancer (10.25 per 100) or newborn with a frequency of 8.73 per 100. PMID- 1309136 TI - [1st isolation of Yersinia enterocolitica in Algeria]. AB - Yersinia enterocolitica has been researched in 200 samples of human stools, 40 animals excrements, 38 specimens of soils and 46 of water; the microorganism has been recovered in respectively 3.5%, 10%, 10.5% and 26% out of the total of samples examined; the strains isolated belong to different Wauter's biotype scheme but the biotype 1 is the most predominant except in soil samples. None of biotype 2 and 4, admitted to be adapted to man, has been isolated from human stools. We think that the notion of adaptation of a given biotype to a given host must be reviewed. These data, although they demonstrate the existence of yersinia enterocolitica in Algeria, because of the small number of samples examined, do not reflect exactly the real incidence of the infection caused by this microorganism. PMID- 1309137 TI - [Production of a vaccine against enterotoxemia from Clostridium perfringens strains isolated in the field]. AB - We have isolated eight strains of C. perfringens from cases of enterotoxaemia. Five of these strains have revealed themselves toxic with respective types (type "A":2, type "C":2, type "D":1). In order to produce anti-enterotoxaemia vaccine, we have proceeded at the cultivation in fermenter of isolated strains and reference strains CWA 35, CWC and CWD AF. At the end of fermentation, we have evaluated the two following parameters: obtained biomass, and toxin titers. With the two classes of strains we reached an important biomass but toxins titers relatively weak comparatively to that which is usually required. It will be necessary then, to demonstrate the immunogen value of the produced vaccines by testing their efficacity. PMID- 1309138 TI - [Newcastle disease in Algeria. Study of the pathogenic properties of Newcastle disease virus strains isolated in Algeria]. AB - The Newcastle disease in Algeria: Study of pathogenic properties of the Newcastle disease viral strains isolated in Algeria. The study of pathogenic characters of 14 strains of Newcastle disease virus isolated from 1972 to 1982 was carried out: The following testS were realized: the mean lethal time for the chicken embryo, the pathogenic power index by intravenous way, the pathogenic power index by intracerebral way, the hemagglutination spectrum and the thermal stability of the hemagglutination. In short we can say that these isolated 14 strains are fast growing. PMID- 1309139 TI - [Result of the refinement of a technique for the isolation and identification of Campylobacter from food commodities]. AB - Campylobacter jejuni has been researched in raw milk, skin and excrement of chicken. All milk samples are negatives but 66% of chicken skin and 12% of chicken excrements are positives. An enrichment phase using brucella broth added with horse blood and antibiotics is necessary. PMID- 1309140 TI - [Bacteriologic quality of the prepared dishes in cafeterias]. AB - In this work, we reports results of bacteriologic analysis of 352 cooked meals (vegetables, meats, desserts). Although, 32% of analysed samples are bacteriologically good, 68% are contamined either by S.P.C but potentially dangerous either by pathogenic bacteria involved in food-born infections. PMID- 1309141 TI - [Visceral leishmaniasis in Algeria. Evolution of visceral leishmaniasis in the Grande Kabylie area (1985-1990)]. AB - The authors report 285 cases of visceral leishmaniasis recorded over a 6 year period from 1985-1990 in the Wilaya of Tizi-Ouzou (Grande Kabylie). The authors report a resurgence of this disease during the last years, with a 5 human cases per 100,000 annual prevalence and a 6 per cent of rate death, the most active part of mediterranean area appears to be the region of Grand-Kabylie. A control program in the Wilaya of Tizi-Ouzou is proposed. PMID- 1309142 TI - [Various isolation and enrichment media for isolating Yersinia enterocolitica]. AB - Study of different isolation and enrichment media for recovering Yersinia enterocolitica has been carried out. The best data have been obtained after enrichment in phosphate buffer with sorbitol and bile salts, followed by a decontamination with Aulisio's KOH and streaking into Hectoen medium. PMID- 1309143 TI - [Visceral larva migrans syndromes: reflections on various cases of toxocariasis]. AB - The authors selected among 5 diagnosed cases of larva migrans. In this study, the authors reported a review of this disease. PMID- 1309144 TI - [Production of monoclonal antibodies against a wild strain of rabies virus]. AB - Production of monoclonal antibodies against a wild strain of rabies virus. Cell fusion of SP 2/O, a murine myeloma against a wild strain of rabies virus has originated five monoclonal antibodies (M.A.) specific for virus nucleocapsid , one M.A. specific for virus glycoprotein and one M.A. specific for a viral membrane protein. PMID- 1309145 TI - [Rapid micromethod for CH50 determination using an algorithm]. AB - The titration of haemolytic complement in biological liquid cause inconvenient in calculating concentration, it was long and fastidious. We report a fast technic based on measure of hemolysis in microplate++ method, which exploitation of results, it does with an appropriate algorithm. PMID- 1309146 TI - [Comparative activities in vitro of 4 quinolones (nalidixic acid, pefloxacin, norfloxacin, ofloxacin) on 13 bacterial species]. AB - Nalidixic acid and three fluoroquinolones were tested on 389 strains belonging to 13 bacterial species, all isolated in Algeria. Ofloxacin, norfloxacin and pefloxacin have the same activities on E. coli, Acinetobacter and S. aureus. Norfloxacin has the best activity on Proteus, Enterobacter, Shigella and Klebsiella. Norfloxacin and ofloxacin have the same activities on S. typhi, Salmonella and choleric Vibrio. Norfloxacin has the same activity than pefloxacin on P. aeruginosa. It is necessary to prescribe a quinolone in the right way and to consider the pharmacokinetic properties. PMID- 1309147 TI - [Resistance to new quinolones among the enterobacteria]. AB - We report the isolation of 10 strains of enterobacteriaceae with a new quinolone's resistance. This resistance was detected by a diminution of inhibition's diameter around the disk of pefloxacin , and confirmed by the determination of Minimal Inhibiting Concentrations (M.I.C.). These strains, moreover multiresistant to multiple antibiotics, were isolated from patient's urines with repetitive urinary tract infections (paraplegics, lithiasic patients). None of this patients was treated by new quinolones. The incorrect use of old quinolones is probably responsible for the selection of this new quinolone's resistance. PMID- 1309148 TI - [Peritonitis caused by Nocardia farcinica in a patient undergoing continuous ambulatory peritoneal dialysis (note)]. AB - We report here an isolation of bacteria genus Nocardia, Nocardia farcinica, in a dialysis liquid of a renal insufficiency patient treated by continuous ambulatory peritoneal dialysis (C.A.P.D.). Real peritonitis was due to infection with this bacteria, eliminated after an adapted antibiotherapy. This observation is interesting first because of the rare occurrence of Nocardia's peritonitis in the patients on CAPD, and secondly in relation with the species of Nocardia, Nocardia farcinica, less known than Nocardia asteroides but not less pathogenic. PMID- 1309150 TI - Idiopathic dystonia. Clinical profile of 76 Brazilian patients. AB - Dystonia may be classified by age of onset (childhood, adolescence, adult onset), body distribution of the abnormal movements (focal, segmental, unilateral, multifocal and generalized) and etiology (idiopathic and symptomatic). We studied 76 patients with idiopathic dystonia among 122 cases of dystonic syndrome (62.3% of the total). There were 48 female and 28 male patients. Adult-onset focal dystonia was the most frequent feature (37 patients). The onset of generalized dystonia was more frequently seen under the age of 20, whereas focal and segmental dystonia usually started over this age. Postural tremor of the hands was observed in 19.7% of the patients. Spasmodic torticollis was the most prevalent form of dystonia overall. Except for writer's cramp, which occurred more frequently in males, and generalized dystonia, which was equally divided between sexes, all other forms were more frequent in females. Our data suggest that differences in racial origin, social and economical status and environmental factors do not account for a different manifestation in dystonia pattern. PMID- 1309149 TI - Is multiple sclerosis in Brazil and Asia alike? AB - The clinical picture of 67 consecutive patients with definite multiple sclerosis in Belo Horizonte, Brazil, was analysed. There were 20 patients with the predominant optic-spinal form of the disease and eight with Devic's disease. Visual loss occurred in 43% of the cases as the presenting symptom and in 84% in the course of the illness. Symptoms related to spinal cord and cerebellar involvement were observed in 64% and 52% respectively. The high prevalence of visual and spinal abnormalities at onset and during the course of the illness, the lesser common involvement of the cerebellum and the relative frequency of Devic's disease make multiple sclerosis in Brazil similar to that observed in Eastern countries in distinction to the clinical pattern seen in the United States and Europe. PMID- 1309152 TI - Carrier detection of Duchenne and Becker muscular dystrophy using muscle dystrophin immunohistochemistry. AB - To ascertain whether dystrophin immunohistochemistry could improve DMD/BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, EMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measurements, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy. improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy. PMID- 1309151 TI - [Early differentiation between Duchenne and Becker muscular dystrophy: clinical, laboratory, electrophysiology, histochemical, and immunohistochemical study of 138 cases]. AB - 194 clinical, laboratory, electrophysiologic, histological, histochemical and immunohistochemical parameters were studied through statistical analysis in 112 cases of Duchenne muscular dystrophy (DMD) and in 26 cases of Becker muscular dystrophy (BMD). It was found a significant statistical difference (p < 0.05) between the two groups concerning the age of evaluation, beginning of symptoms, difficulty in walking, running, climbing and going downstairs, frequent falling down, support to walk, localized muscle pain, stopping climb stairs, and inability to walk. Muscle biopsy showed statistically significant (p < 0.05) differences between the two groups regarding the intensity of connective tissue and focal adipose tissue proliferation, presence of diffuse rounded atrophic and angulated fibers, diffuse hypertrophic and splitting fibers. There were also differences regarding excessive internal fibers nuclei, hypertrophic types 1 and 2 fibers, angulated atrophic fibers and focal increasing in the NADH-TR, angulated atrophic fibers in non-specific esterase, and accumulated NBT in the periphery of fibers in succinic dehidrogenase. Isolatedly muscle biopsy gave the correct diagnosis in 52.7% of DMD cases and in 69.2% of BMD cases. Dystrophin detection by immunofluorescence (60 cases) showed: absence in 87.0% of fibers in DMD cases, and sarcolemmal membrane discontinuites in all BMD cases. The muscle biopsy diagnosis had an agreement with the dystrophin results in 82.6% of DMD cases and 71.4% of BMD cases. PMID- 1309153 TI - [Psychosocial approach of the epileptic patient: analysis of 30 adults]. AB - Psychosocial aspects of patient's life were analysed in 30 patients with epilepsy aged over 18 years old. At this age people usually are apt by themselves to exert several psychosocial activities. Professional, familial, social, scholar, affective, sexual and religious activities were evaluated in our group of patients. Results evidence that epileptic patients studied show several kinds of difficulties in their psychosocial adjustment. PMID- 1309154 TI - CSF in 85 patients with AIDS and CNS cryptococcosis. AB - In an eight years time period (July 1984-June 1992) CSF samples of 40718 patients were studied, and 610 were from patients with AIDS clinically diagnosed and immunologically confirmed through HIV antibodies detection. Among opportunistic infections detected in them 85 were CNS cryptococcosis. For the purpose of this study the CSF of these 85 patients are the AIDS group of CNS cryptococcosis. For comparison, CSF data from 50 patients with CNS cryptococcosis but without AIDS were taken (non-AIDS group); in this group, 22 patients were immunosuppressed after renal transplant. In AIDS group, the more frequent CSF findings were: yeast presence at direct exam (Fuchs-Rosenthal cell counting chamber), growing of the yeast in cultures, and gamma globulins increase. In non-AIDS group were more frequent: hypercytosis, neutrophil cells presence, and total protein increase. Differences between the two groups are discussed taking into account CNS/CSF immune changes induced by HIV infection. It is concluded that in CNS cryptococcosis of patients with AIDS the CSF evidenced more extensive signs of the fungal opportunistic infection than signs of inflammatory response to the infection. The latter were more prominent among patients of the non-AIDS group of CNS cryptococcosis. PMID- 1309155 TI - Neurotoxoplasmosis and AIDS. Cerebrospinal fluid analysis in 96 patients. AB - The behavior of CSF inflammatory pattern in patients with AIDS and/or toxoplasmosis of the CNS is studied in 176 patients, divided in three groups. In the first group, 96 patients with toxoplasmosis and AIDS are considered; in the second group, 50 patients with toxoplasmosis without AIDS; in the third group, 30 AIDS patients without toxoplasmosis nor any other opportunistic infection. It is possible to conclude that patients with toxoplasmosis associated to AIDS exhibit CSF inflammatory pattern similar to patients with neurotoxoplasmosis without AIDS, except in respect to gamma globulin rates for which a cumulative effect can be detected. PMID- 1309156 TI - [Conservative treatment of laminar extradural hematomas in children]. AB - We successfully treated by nonsurgical methods 15 children with laminar epidural hematomas (EH), with minimal neurological symptoms and no signs of brain herniation. These EH were discovered 30 minutes to 5 days after head injury. The majority were localized in the parietal region. All children recovered without surgery from 2 to 12 days after hospitalization and all had evidence on CT scan of spontaneous clot reabsorption. We discuss the criteria for patient selection for this kind of treatment on EH in children. PMID- 1309157 TI - [Primary necrosis of the corpus callosum (Marchiafava-Bignami's disease): report of 5 cases]. AB - The clinicopathological study of five autopsied cases of Marchiafava-Bignami disease is reported. The demyelination of the central portion of the corpus callosum is the major characteristics of the disease. In two cases the demyelination also involved the anterior and posterior commissures. There is a clear relationship to alcoholism and malnutrition in the cases reported in the present study. PMID- 1309158 TI - [Basal ganglia calcifications in children]. AB - We report the study of four children with bilateral basal ganglia calcifications (BGC) visualized on CT scan. Epilepsy was the clinical manifestation of three patients whose laboratory investigation revealed abnormal calcium metabolism. The first aim of this paper is to call attention to a treatable entity that can cause epileptic syndromes in infancy and childhood. The second purpose is to review the literature comparing with our fourth child who presented encephalopathy with BGC. PMID- 1309159 TI - Diffuse encephalic calcification. A case report. AB - The basal ganglia calcification is known since the last century but with the new neuroimage techniques (CT scan) its diagnosis became more frequent specially in asymptomatic patients. The authors report a case with non-familial primary diffuse encephalic calcification with exuberant calcifications on cerebral hemispheres, cerebellum and brain stem, seen on CT scan. PMID- 1309160 TI - [Intracranial saccular aneurysm: report of 3 cases in a same family]. AB - The authors report the cases of three patients from the same family, all with intracranial saccular aneurysm (left carotid artery, anterior communicating artery, and middle cerebral artery). All three patients were operated on with good recovery and no complications. The authors call attention for some etiopathogenic aspects of familial saccular aneurysms. PMID- 1309161 TI - Segmental myoclonus and basilar artery. Giant aneurysm. Case report. AB - A 70 years-old man was admitted at our hospital because of unstable angina pectoris. He had essential hypertension and right hemiplegia from a ischemic stroke two years before admission. On neurologic examination, it was found mental disorientation, unstable emotionality, right spastic hemiparesis with right Babinski sign, and segmental myoclonus affecting the superior lip and the palate (palatal nystagmus) on the right side. On the CT scan, a giant aneurysm of the basilar artery was detected. We conclude that the segmental myoclonus could be explained by ischemic lesions in the Guillain-Mollaret triangle. PMID- 1309162 TI - [Parkinsonism secondary to ethylene oxide exposure: case report]. AB - Ethylene oxide is a gas widely used in the production of industrial chemicals. It is also used to sterilize heat-sensitive medical supplies. Previous reports of acute and chronic exposure have described neurotoxic effects like peripheral neuropathy and cognitive impairment. We describe a pure parkinsonian syndrome following acute ethylene oxide intoxication. A 39-years-old male was referred to our Movement Disorders Clinic for evaluation of a parkinsonian syndrome. He was acutely exposed to ethylene oxide four years before and remained comatose for three days, and gradually regained consciousness. At that time he showed a global parkinsonian syndrome including bradykinesia, rigidity and rest tremor, with a severe motor disability; no other neurological disorders were found. The symptomatology was partially controlled with biperidene and levodopa plus carbidopa. Two years later he developed L-dopa induced dyskinesias. Four years after the intoxication he was evaluated at our clinic. General examination showed no abnormalities. Neurologic examination revealed a normal mental status. Motor evaluation disclosed moderate bradykinesia, rigidity and rest tremor, shuffling gait, poor facial mimic, stooped posture, and his speech was low and monotonous; deep tendon reflexes were brisk. The Hoehn-Yahr disability score was degree IV. Routine laboratory and radiological exams showed results within normal limits. The CSF examination was normal. Brain computed tomography and magnetic ressonance were normal. A trial with bromocriptine and levodopa plus carbidopa did not improve dyskinesia, and he was put on a schedule including amantadine and biperidene with improvement to grade III in Hoehn-Yahr scale. In the present case there was a clear relation between the acute exogenous intoxication and irreversible parkinsonism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309163 TI - Granuloma formation and arterial thrombosis following cotton wrapping of an intracranial aneurysm. A case report. AB - The authors report the case of a patient whose left middle cerebral artery aneurysm was wrapped with cotton. Occlusion of the middle cerebral artery, probably secondary to a foreign-body inflammatory reaction, developed late in the postoperative course. A computerized tomography scan revealed cerebral infarct, and an enhancing expansive lesion at the site of the aneurysm suggesting the formation of a granuloma. These findings are discussed and the literature is reviewed. PMID- 1309164 TI - [Schwannomatosis: report of a new case]. AB - Schwannomatosis is a rare disorder, still not quite well defined, seldom described in the literature. In this paper we report the case of male. Patient, 52 years old, who in the last 30 years developed five subcutaneous tumors within his limbs peripheral nerves, which histologically proved to be schwannomas. A brain computed tomography showed a partially calcified tumor in the left temporal lobe which most likely was a meningioma. A thorough clinical examination was unable to find signs of type I or type II neurofibromatosis. The present condition, probably a form of phacomatosis, has to be distinguished from neurofibromatosis and is considered as an independent clinical entity whose origin still awaits further detailed investigations. PMID- 1309165 TI - Kleptomania, mood disorder and lithium. AB - Kleptomania has been found in association with major depression in a fairly large number of reports in recent years. We describe a patient with concurrent DSM-III R Bipolar Mood Disorder and Kleptomania, whose symptoms remitted completely, apparently in response to lithium therapy, which raised the possibility that pharmacological treatment may benefit kleptomania. Further studies are needed to establish the possible relationship between kleptomania, mood disorders and lithium therapy. PMID- 1309166 TI - [Definitively: epilepsy is not a disease]. AB - The author analyses past concepts which still hold good today. Such concepts regard epilepsy as a mental disease and the epileptic is usually taken as someone suffering from a severe mental disorder, tending to criminal behaviour. The author proves, taking into account various statements from prominent personalities in the scientific world, that epilepsy is neither a mental disease nor a disease in its own sense, and that the epileptic has not an aggressive behaviour. PMID- 1309167 TI - [Opinion: the case-scandal of triazolam]. PMID- 1309169 TI - Gold weights in upper lids. PMID- 1309168 TI - Adenine nucleotide concentrations and energy charge in muscle of chronic haemodialysis patients. AB - Adenine nucleotide concentrations and energy charge ratios were measured in muscle samples collected during transplant surgery of 7 patients suffering from chronic renal failure and undergoing haemodialysis. The energy charge ratio of 0.75 in the muscle of transplant patients was significantly lower (p less than 0.01) than that of 0.89 found in muscle from controls. The lower energy charge ratio and increased concentrations of adenosine diphosphate and adenosine monophosphate may contribute to the patients' reduced exercise ability and their poor metabolic state. PMID- 1309170 TI - Brain death. Occurs only with destruction of the cerebral hemispheres and the brain stem. PMID- 1309171 TI - The basis of the FDA's decision on breast implants. PMID- 1309172 TI - Mycobacterial spindle cell pseudotumor of lymph nodes. AB - Two cases of spindle cell pseudotumor in the lymph nodes of patients with acquired immunodeficiency syndrome caused by mycobacterial infection are reported and the literature reviewed. The lesions mimicked neoplasms because they were composed predominantly of spindle cells arranged in a storiform pattern. Most of the spindle cells were phagocytic cells that contained large amounts of mycobacteria. It is important for the pathologist to recognize the lesion so that a prompt tissue diagnosis can be provided because specific therapy is available. PMID- 1309173 TI - Estimating severity of chronic heart failure: a clinical challenge for the 1990s. PMID- 1309174 TI - Brachial plexus palsy: an old problem revisited. AB - OBJECTIVES: It is an almost assumption in obstetric literature that brachial palsy is due to extreme lateral traction on the fetal head during the last phase of delivery. In contrast, there have been reports in the neurologic literature of probable intrauterine origin of brachial plexus palsy. Data to dispute or support the latter view were sought. STUDY DESIGN: With this overview in mind, our perinatal data base was searched for all instances of shoulder dystocia and independently for all diagnoses of brachial plexus impairment. RESULTS: Seventeen instances of brachial plexus impairment associated with shoulder dystocia were found. Twenty-two instances of brachial plexus impairment without mention of shoulder dystocia were ascertained. The characteristics of the two groups were remarkably different, especially in birth weight and in maternal age and parity. CONCLUSIONS: The data are strongly suggestive that intrauterine maladaptation may play a role in brachial plexus impairment. Brachial plexus impairment should not be taken as prima facie evidence of birth process injury. PMID- 1309175 TI - Practical testing of solid-state stability of pharmaceuticals. PMID- 1309176 TI - Inflammatory myoglandular polyps of the colon and rectum. A clinicopathological study of 32 pedunculated polyps, distinct from other types of polyps. AB - Hitherto unclassified colorectal polyps were identified in 32 patients (23 men and 9 women; mean age, 53 years). The only symptom, which was observed in less than half the patients, was passage of blood or occult blood. Endoscopic examination revealed solitary pedunculated, red polyps with a smooth surface. These polyps were found in the left colon, especially in the sigmoid. Their characteristic features were inflammatory granulation tissue in the lamina propria mucosae, proliferation of smooth muscle, and hyperplastic glands with occasional cystic dilatation. The etiology of this type of polyp is unknown, but it could involve chronic trauma from the fecal stream and from peristalsis of the bowel. These polyps can be differentiated from juvenile polyps and inflammatory polyps by the presence of abundant smooth-muscle cells in the inflamed lamina propria mucosae. They also can be differentiated from Peutz-Jeghers polyps, which appear as hamartomatous structures with tree-like proliferation of muscularis mucosae covered by colonic mucosa without inflammatory granulation tissue. Their locations and macroscopic appearance distinguish these polyps from mucosal prolapse syndrome and polyps developed after colostomy. In addition, these new polyps differ from inflammatory cap polyps in that they lack a fibrin cap. We propose the name inflammatory myoglandular polyps for these polyps, which are distinct clinicopathologically from other types of colorectal polyps. PMID- 1309177 TI - Reevaluation of secular trends in depression rates. AB - Results of numerous community surveys of psychiatric illness suggest a striking change in the occurrence of depression, with younger generations experiencing higher lifetime risk and earlier age of onset. Data from the National Institute of Mental Health Epidemiologic Catchment Area Survey (a cross-sectional survey of psychiatric morbidity in five US communities conducted between 1980 and 1984) were reexamined for evidence of methods effects which might contribute to these unexpected findings. A pattern of higher lifetime risk and earlier age of onset among recent birth cohorts was observed for every psychiatric disorder examined, with schizophrenia, major depression, and panic disorder showing equally strong trends. For respondents of all ages, reported first onset of major depression clustered in the 10-year period prior to the study interview, in contrast to the expectation that older respondents would report onset in early adulthood. Examination of individual psychiatric symptoms revealed a nearly universal pattern of decreasing lifetime prevalence among older respondents, a reversal of the expected accumulation of lifetime symptoms with age. These findings suggest that effects of study methods may contribute to the apparent temporal trends in prevalence of depression and that cross-sectional surveys may underestimate lifetime psychiatric morbidity among older respondents. Generational changes in the lifetime risk of depression or other psychiatric disorders may not be reliably assessed by cross-sectional survey data. PMID- 1309178 TI - Truth telling to the patient. PMID- 1309179 TI - The laryngeal mask airway for intraocular surgery: effects on intraocular pressure and stress responses. AB - Tracheal intubation, performed routinely during general anaesthesia in patients undergoing intraocular surgery, may have adverse effects on cardiovascular function and intraocular pressure. This study assessed the suitability of the laryngeal mask airway (LMA) as a substitute for tracheal intubation. Intraocular and systemic pressor effects, heart rate changes and catecholamine concentrations were measured in two groups of 10 patients receiving standardized anaesthesia with either a tracheal tube (TT) or a LMA. There were significantly smaller changes in the pressor responses to insertion and in concentrations of catecholamines at critical times in the anaesthetic sequence in the LMA group. Mean (SEM) rate-pressure product was significantly smaller in the LMA group compared with the TT group after both insertion (8276 (730) vs 13307 (1348), P < 0.01) and removal (10152 (595) vs 14137 (1044), P < 0.01) of the airway device. The change in intraocular pressure was significantly less in the LMA group at all time points after airway instrumentation than that in the TT group, with the greatest difference after extubation (-2.3 (2.4) mm Hg vs 14.5 (3.4) mm Hg, P < 0.01). PMID- 1309180 TI - Drug treatment of panic disorder. Reply to comment by Marks and associates. PMID- 1309181 TI - Mechanistic investigation of medium-chain fatty acyl-CoA dehydrogenase utilizing 3-indolepropionyl/acryloyl-CoA as chromophoric substrate analogues. AB - The CoA derivative 3-indolepropionyl-CoA (IPCoA) serves as a competent pseudosubstrate for the medium-chain fatty acyl-CoA dehydrogenase (MCAD) catalyzed reaction. The reaction product trans-3-indoleacryloyl-CoA (IACoA) exhibits a characteristic UV-vis absorption spectrum with lambda max = 367 nm and epsilon 367 = 26,500 M-1 cm-1. The chromophoric nature of IACoA allows us to measure the direct conversion of substrate to product (at 367 nm) without recourse to absorption signals for either the enzyme-bound flavin or the coupling electron acceptors, as well as probe the enzyme site environment. The interaction of IACoA with medium chain fatty acyl-CoA dehydrogenase (MCAD)-FAD is characterized by resultant (spectra of the mixture minus the individual components) absorption peaks at 490, 417, and 355 nm. These absorption peaks increase in magnitude as the pH of the buffer media decreases. Transient kinetic analysis for the interaction of MCAD-FAD with IACoA suggests that the formation of the enzyme-IACoA complex proceeds in two steps. The first (fast) step involves the formation of an E-IACoA collision complex, which [formula: see text] is isomerized (concomitant with changes in the protein structure) to an E*-IACoA complex in the second (slow) step. We have studied the effect of pH on Kc, k2, and k-2. While Kc shows practically no dependence on pH (within a 2-fold variation between pH 6.0 and 9.5), k2 and k-2 show a strong dependence on pH. Both k2 and k-2 exhibit a sigmoidal dependence on the pH of the buffer media, with pKa's of 7.53 and 8.30, respectively. In accordance with the model presented herein, the pKa of 7.53 represents an enzyme site group which is involved in the interaction with IACoA within the E-IACoA collision complex. This pKa is perturbed to 8.30 upon isomerization of the collision complex. The pH-dependent changes in k2 and k-2 are such that the equilibrium distribution between E-IACoA and E*-IACoA is favored to the latter complex (by about 20-fold) at lower pH than at higher pH. A cumulative account of the spectral, kinetic, and thermodynamic properties of the enzyme-IACoA complexes has allowed us delineate the microscopic pathway by which the E-IACoA isomerization (presumably via protein conformational changes) is coupled to the proton equilibration steps. PMID- 1309182 TI - Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. AB - OBJECTIVES: The objectives of this study were to present data on eight patients with recurrent episodes of aborted sudden death unexplainable by currently known diseases whose common clinical and electrocardiographic (ECG) features define them as having a distinct syndrome different from idiopathic ventricular fibrillation. BACKGROUND: Among patients with ventricular arrhythmias who have no structural heart disease, several subgroups have been defined. The present patients constitute an additional subgroup with these findings. METHODS: The study group consisted of eight patients, six male and two female, with recurrent episodes of aborted sudden death. Clinical and laboratory data and results of electrocardiography, electrophysiology, echocardiography, angiography, histologic study and exercise testing were available in most cases. RESULTS: The ECG during sinus rhythm showed right bundle branch block, normal QT interval and persistent ST segment elevation in precordial leads V1 to V2-V3 not explainable by electrolyte disturbances, ischemia or structural heart disease. No histologic abnormalities were found in the four patients in whom ventricular biopsies were performed. The arrhythmia leading to (aborted) sudden death was a rapid polymorphic ventricular tachycardia initiating after a short coupled ventricular extrasystole. A similar arrhythmia was initiated by two to three ventricular extrastimuli in four of the seven patients studied by programmed electrical stimulation. Four patients had a prolonged HV interval during sinus rhythm. One patient receiving amiodarone died suddenly during implantation of a demand ventricular pacemaker. The arrhythmia of two patients was controlled with a beta adrenergic blocking agent. Four patients received an implantable defibrillator that was subsequently used by one of them, and all four are alive. The remaining patient received a demand ventricular pacemaker and his arrhythmia is controlled with amiodarone and diphenylhydantoin. CONCLUSIONS: Common clinical and ECG features define a distinct syndrome in this group of patients. Its causes remain unknown. PMID- 1309183 TI - Medications in older patients. AB - Adverse drug reactions are common in persons aged 65 and older and are associated with increased morbidity and mortality. A heightened susceptibility to adverse reactions is due to a number of factors, including an increased incidence of disease, multiple drug use, and altered pharmacokinetic and pharmacodynamic properties of many drugs. The risk of drug interactions increases with the number of medications taken. Adverse drug reactions can be prevented through prudent prescribing practices, patient education, and adequate monitoring of drug efficacy and side effects. Several types of medications are of particular concern, including many antihypertensive agents, drugs with anticholinergic effects, psychoactive medications, and nonsteroidal anti-inflammatory drugs. Some drugs, such as histamine H2-receptor antagonists, are relatively safe but are overprescribed. Data regarding the risks associated with these problem drugs are presented, with recommendations for safe and effective treatment alternatives. PMID- 1309184 TI - Hypotonous maculopathy after trabeculectomy with subconjunctival 5-fluorouracil. AB - Long-term success in trabeculectomy has been enhanced in recent years by postoperative subconjunctival 5-fluorouracil injections and intraoperative mitomycin C applications. During 1990 and 1991, after trabeculectomy with a small scleral flap (2 x 3 mm) augmented by antimetabolite therapy, hypotonous maculopathy developed in eight eyes of six patients. The maculopathy was characterized by loss in visual acuity, retinal striae, and choroidal folds without evidence of vascular leakage. The average loss in visual acuity was four Snellen lines. Visual acuity did not return to preoperative levels even when the hypotony could be reversed. Reversing the hypotony with various strategies aimed at stimulating subconjunctival scarring has been relatively ineffective. During that same period, an additional seven eyes in six patients had prolonged hypotony but without development of maculopathy. Features common to patients who developed maculopathy included age (mean age, 46 years; range, 32 to 60 years) and myopia (mean, -7.5 diopters; range, -0.75 to -11.75 diopters). The patients with hypotony but no maculopathy were older (mean age, 73 years; range, 63 to 82 years) and were closer to emmetropia (mean, -1.11 diopters; range, +1.50 to -9.00 diopters). The means of the ages and refractive errors were statistically significantly different in the two groups (P = .007 and .04, respectively). Trabeculectomy with adjunctive antifibrosis therapy should be used with caution in young myopic patients. PMID- 1309185 TI - The breast is close to the heart. PMID- 1309186 TI - Cerebral palsy in twins. AB - Eighty-six children with cerebral palsy (CP) born as a product of twin pregnancies were studied. Data regarding their co-twins were also gathered. The authors' findings suggest that (1) monozygotic twins have a higher risk of CP than dizygotic twins, (2) twin order at birth does not seem to be a relevant factor in the etiology of CP, (3) mothers less than 24 or more than 34 years of age had the highest incidence of children with CP as a product of a twin pregnancy, and (4) the data do not support a genetic basis for the disease. PMID- 1309187 TI - Allergic reaction to spiramycin. PMID- 1309188 TI - Treatment of allergic bronchopulmonary aspergillosis with inhaled corticosteroids. PMID- 1309189 TI - The safety of sevoflurane in humans. PMID- 1309190 TI - Pyogenic granuloma of the cornea after penetrating keratoplasty. AB - An 81-year-old man with metastatic prostate carcinoma underwent a penetrating keratoplasty for phlyctenular keratitis. Two years later he developed a fleshy, vascular mass in the superotemporal corneal graft wound, at the site of prior graft sutures. An excisional biopsy of the mass was performed to rule out metastatic carcinoma. Histopathological findings were consistent with pyogenic granuloma. To our knowledge there have been no prior case reports illustrating pyogenic granuloma as a late complication of penetrating keratoplasty. PMID- 1309191 TI - Bovine gangliosides and acute motor polyneuropathy. PMID- 1309192 TI - Restoring sensation after trigeminal nerve injury: a review of current management. AB - After a year, even the most expert peripheral nerve repair carries a poor prognosis. Early referral and intervention offer the best management of trigeminal nerve injuries. PMID- 1309193 TI - Boronate affinity chromatography. PMID- 1309194 TI - Cross-talk regulation between cyclic AMP production and phosphoinositide hydrolysis induced by prostaglandin E2 in osteoblast-like cells. AB - In cloned osteoblast-like MC3T3-E1 cells, PGE2 stimulated both cAMP accumulation and the formation of inositol trisphosphate (IP3) dose dependently. The cAMP accumulation showed the peak value at 5 min and decreased thereafter, whereas the IP3 formation reached a plateau almost within 10 min and sustained it up to 30 min. The effect of PGE2 on cAMP accumulation (EC50 was 80 nM) was more potent than that on IP3 formation (EC50 was 0.8 microM). 12-O-Tetradecanoyl-phorbol-13 acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, reduced the PGE2-induced cAMP accumulation, whereas 4 alpha-phorbol 12,13-didecanoate, a PKC nonactivating phorbol ester, had little effect on the cAMP accumulation. 1-Oleoyl 2-acetyl-glycerol, a specific activator for PKC, inhibited PGE2-induced cAMP accumulation. TPA had little effect on cAMP accumulation induced by forskolin or NaF, a GTP-binding protein activator. So, the effect of TPA is presumed to be exerted at the point between the PGE2 receptor and Gs. On the other hand, forskolin and dibutyryl cAMP had little effect on the IP3 formation stimulated by PGE2. H-7, a PKC inhibitor, enhanced the PGE2-induced cAMP accumulation in comparison with HA1004, a control for H-7. Our data suggest that PGE2 regulates cAMP production through self-induced activation of PKC. These results strongly suggest that there is an autoregulatory mechanism in PGE2 signaling, and PGE2 modulates osteoblast functions through a cross-talk interaction between cAMP production and phosphoinositide hydrolysis in osteoblast-like cells. PMID- 1309195 TI - Receptors for N-acetylated sugars may stimulate adenylate cyclase to sensitize and tune mechanoreceptors involved in triggering nematocyst discharge. AB - In fishing tentacles of sea anemones, cnidocyte/supporting cell complexes (CSCCs) trigger the discharge of nematocysts following stimulation by swimming prey of specific mechanoreceptors and chemoreceptors located on the supporting cells. Two types of mechanoreceptors have been identified: a contact-sensitive mechanoreceptor (CSM), and a vibration-sensitive mechanoreceptor (VSM). The CSMs become predisposed to initiate nematocyst discharge into static (i.e., nonvibrating) test probes in the presence of submicromolar free and conjugated N acetylated sugars, a process referred to as sensitization. In seawater, the VSMs cause maximal discharge in response to test probes vibrating at 30, 50-55, and 75 Hz, whereas in the presence of submicromolar N-acetylated sugars the VSMs cause maximal discharge into test probes vibrating at 5, 15, 30, and 40 Hz, a process referred to as tuning. Tuning of the VSMs is accompanied by elongation of the stereocilium bundles comprising the VSMs. We report that dibutyryl cyclic-AMP sensitizes CSMs and tunes VSMs to the lower frequencies of 5, 15, 30, and 40 Hz, while cyclic-AMP has no such effects. Endogenous adenylate cyclase activity at the apical plasma membrane of the supporting cells is detectable by cytochemical methods in the presence of N-acetylated sugars but not in seawater alone. By activating adenylate cyclase with L858051, an analogue of forskolin, or by activating the stimulatory form of G proteins (Gs) with cholera toxin, CSCCs are induced to sensitize CSMs and to tune VSMs to the lower frequencies of 5, 15, 30, and 40 Hz. Caged GTP-gamma S also sensitizes CSMs but tunes VSMs to 5, 15, 30, 40, 55, 65, and 75 Hz, suggesting that VSM tuning may be regulated both by Gs and inhibitory G-proteins. Together, these results implicate cAMP as the second messenger for activated supporting cell chemoreceptors involved in sensitizing the CSMs and tuning the VSMs to lower frequencies. PMID- 1309196 TI - Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration. AB - BACKGROUND: In nasopharyngeal carcinoma the primary lesion is often difficult to find. Metastatic lesions occur frequently but are difficult to distinguish from other head and neck tumors. The viral genome of the Epstein-Barr virus (EBV) can be identified in the cells of this carcinoma. METHODS: We used the polymerase chain reaction (PCR) to test for the presence of EBV genomes in 15 samples of metastatic squamous-cell carcinoma of the neck obtained by fine-needle aspiration and in 26 samples obtained by biopsy of lymph nodes. For controls we used disease free lymph nodes from 10 patients with various head and neck tumors, tonsillar tissue from 46 subjects, blood from 59 EBV-seropositive blood donors, and mononuclear cells from 8 patients with fatal lymphoproliferative lesions. RESULTS: Of the 41 malignant lesions examined, only the nine nasopharyngeal carcinomas (one primary lesion and eight metastases) contained EBV genomes. None of the 20 nodes with other types of cancer, the 10 disease-free nodes, or any of the 105 normal control samples contained detectable EBV. In two patients with suspected metastases from occult primary tumors, the presence of EBV was predictive of nasopharyngeal carcinoma; in both cases overt nasopharyngeal carcinoma developed within one year. CONCLUSIONS: In patients with suspected nasopharyngeal carcinoma, fine-needle aspiration can provide tissue for diagnosis by DNA amplification of EBV genomes. The presence of EBV in metastases from an occult primary tumor is predictive of the development of overt nasopharyngeal carcinoma. PMID- 1309197 TI - Head and neck cancer with an occult primary tumor. PMID- 1309198 TI - Hepatitis C virus replication. PMID- 1309199 TI - Hepatitis C virus replication. PMID- 1309201 TI - Reducing the risk for transfusion-transmitted cytomegalovirus infection. AB - OBJECTIVE: To define the groups of patients at risk for transfusion-transmitted cytomegalovirus infection and to define the methods to reduce this risk. DATA SOURCES: English-language publications on transfusion medicine. STUDY SELECTION AND DATA EXTRACTION: Studies were selected that described cytomegalovirus infection in transfusion-dependent patients. Special attention was paid to reports that included observations about the prevalence and clinical manifestations of cytomegalovirus infection and recommendations for the prevention of infection. DATA SYNTHESIS: Some patients with impaired immune responses who have never been exposed to cytomegalovirus are at risk for transfusion-transmitted cytomegalovirus infection. This infection, which is associated with substantial morbidity and mortality, can be avoided by additional screening of blood donors or by special processing of components for transfusion. CONCLUSIONS: Transfusion products that are unlikely to transmit cytomegalovirus infection can be prepared by filtration to remove leukocytes or can be obtained by selecting donors who are seronegative for antibodies to cytomegalovirus. These products are indicated for certain groups of immunosuppressed patients, including pregnant women who are cytomegalovirus seronegative, premature infants of low birth weight who are born to cytomegalovirus-seronegative mothers, cytomegalovirus-seronegative recipients of allogeneic bone marrow transplants from cytomegalovirus-seronegative donors, and cytomegalovirus-seronegative patients with the acquired immunodeficiency syndrome (AIDS). PMID- 1309200 TI - Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis. AB - OBJECTIVE: To determine whether laboratory findings showing antibodies to hepatitis C virus (HCV) in patients with autoimmune hepatitis represent false positive results and to identify possible explanations for true-positive results in these patients. DESIGN: Cross-sectional. SETTING: University-based hospital. PATIENTS: Fifty-two patients with non-A, non-B chronic hepatitis as a control group and 26 patients with classic chronic active autoimmune hepatitis. MEASUREMENTS: Comparison of the results of five kinds of assays of HCV antibodies and HCV RNA. MAIN RESULTS: Of 52 patients with non-A, non-B chronic hepatitis, HCV antibodies (anti-HCV) were detected in 42 patients (81%; 95% CI, 67% to 90%) by a first-generation enzyme-linked immunosorbent assay (ELISA-I), in 39 patients (75%) by Sp42 ELISA, in 37 patients (71%) by RIA-I, in 49 patients (94%) by ELISA II, and in 48 patients (92%) by RIBA-II. We found HCV RNA in 47 patients (90%; CI, 79% to 97%). Of the 26 patients with autoimmune hepatitis, anti-HCV were detected in 23 patients (88%; CI, 70% to 98%) by ELISA-I, in 12 (46%) by both RIA I and Sp42 ELISA, in 20 (77%) by ELISA-II, and in 9 (35%) by RIBA-II. However, HCV RNA was found in only five of these patients (19%; CI, 7% to 39%). None of our patients, including controls, had antibodies to superoxide dismutase. Of the 21 patients who had autoimmune hepatitis that was completely responsive to steroid therapy, 18 had anti-HCV by ELISA-I, but 13 of these patients had negative results by RIBA-II, and only two patients had HCV RNA. Of the five patients who did not respond to steroid treatment, all had anti-HCV by ELISA-I, four had negative results by RIBA-II, and three had HCV RNA. CONCLUSIONS: Testing for HCV antibodies in patients with autoimmune hepatitis frequently elicits positive results when the ELISA-I or ELISA-II tests are used. Most of these appear to represent false-positive results because HCV RNA is usually absent from the serum. Such false positivity may result from previous infection with HCV or from cross-reaction of an epitope of HCV. Other patients with apparent autoimmune hepatitis who fail to respond to corticosteroid therapy may actually have chronic hepatitis C (or other non-A, non-B hepatitis) infection. PMID- 1309202 TI - Combination therapy for HIV infection: getting closer. PMID- 1309203 TI - Heterogeneity of radiosensitivity in a human glioma cell line. AB - Sixteen clones were isolated from an early-passage human glioma cell line (IN859) and have been found to show variation in several biological characteristics including DNA content, modal chromosome number, and morphology. In addition, heterogeneity of radiosensitivity was detected: the doses that gave a surviving fraction of 0.01 varied by a factor of approximately 1.5. The most sensitive (clone 6) and the most resistant (clone 9) clones were selected for further study; their surviving fractions at 2Gy (SF2) were 0.37 and 0.64, respectively. When compared at a fixed radiation dose the sensitive clone surprisingly demonstrated greater split-dose recovery than the resistant clone; it also showed greater low dose-rate sparing. PMID- 1309204 TI - Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial. AB - Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months. PMID- 1309205 TI - Long term tolerance of thoracic organs to intraoperative radiotherapy. AB - The tolerance of mediastinal structures to intraoperative radiotherapy (IORT) was investigated in 3 separate animals trials using 49 adult foxhounds and one limited Phase I trial in 4 patients with Stage II or III non-small cell lung cancer (NSCLC). The 1- to 2-year results of these trials have been previously reported with significant toxicity found at dose levels over 20 Gy. We now report the results of five dogs reserved for long term studies and one Stage II NSCLC patient alive at 5 years. Two dogs received 20 Gy IORT and one received 30 Gy IORT to the esophagus, all three to a single 6 cm field with 9 MeV electrons. One control dog underwent surgery without irradiation. One dog received 20 Gy IORT to a single 5 cm mediastinal field with 13 MeV electrons following left pneumonectomy. At 5 years, all five dogs reserved for a long term evaluation were alive and evaluable with minimal endoscopic and radiographic abnormalities. The one patient alive at 5 years for evaluation received 25 Gy IORT to two matched 6 cm fields with 13 MeV electrons. She has stable dyspnea on exertion and there is no evidence of cancer by endoscopy. We conclude, based on these limited data, that IORT in the mediastinum may be safe at dose levels that do not exceed 20 Gy, and further careful evaluation at these lower treatment doses is warranted to determine efficacy. PMID- 1309206 TI - Calcium channels and nifedipine inhibition of serotonin-induced [3H]thymidine incorporation in cultured cerebral smooth muscle cells. AB - Cultures of smooth muscle cells were prepared from the basilar artery of adult guinea pigs. Passaged cultures (10-30 passages) that expressed serotonin receptors were studied using [3H]thymidine incorporation. When tested in quiescent medium, serotonin potently stimulated [3H]thymidine incorporation (EC50 of 31 nM) by as much as 400% at 24 h. The number of cells was not significantly increased at 24 or 48 h. At concentrations of 10(-8)-10(-5) M 5-HT, [3H]thymidine uptake was reduced 40-50% by the dihydropyridine Ca2+ channel blocker, nifedipine (1 microM). To demonstrate a possible mechanism for the sensitivity to nifedipine, Ca2+ currents were measured using the whole cell patch clamp technique. The cells expressed dihydropyridine-sensitive L-type Ca2+ channels, but not other subtypes of Ca2+ channels, as indicated by the kinetic and voltage dependent characteristics of the current and by the stimulatory effect of Bay K 8644. The magnitude of the Ca2+ currents was related exponentially to the membrane surface area, measured as cell capacitance. These data support the association of dihydropyridine-sensitive Ca2+ channels with mitogenesis in vascular smooth muscle, and suggest an alternate mechanism of action for the beneficial effect of dihydropyridines in prophylaxis of cerebral vasospasm. PMID- 1309207 TI - Successful management of inferior vena cava and right atrial nephroblastoma tumor thrombus with preoperative chemotherapy. AB - Involvement of inferior vena cava (IVC) by tumor thrombus occurs in up to 10% of patients with nephroblastoma. Right atrial involvement by tumor thrombus is much less frequent. Four patients presenting with advanced nephroblastoma were diagnosed as having IVC involvement with tumor thrombus. Two of these patients had in addition thrombus extending up to the right atrium. All 4 patients were treated with preoperative chemotherapy (vincristine, actinomycin D, 4-epi Adriamycin). Nephrectomy was subsequently performed without undue difficulty on all 4 patients. The intravascular tumor thrombus had completely cleared in all 4 patients and most of the primary renal tumor was necrotic. The results obtained with preoperative chemotherapy as given to these patients mediates strongly against difficult surgery being undertaken as primary treatment for such patients. PMID- 1309209 TI - Staging designation for bilateral Wilms' tumors. PMID- 1309208 TI - Hepatocellular carcinoma associated with arteriohepatic dysplasia in a 4-year-old girl. AB - Hepatocellular carcinoma and obliterated hepatic bile duct were found at postmortem examination in a 4-year-old girl with arteriohepatic dysplasia (Alagille's syndrome). AFP level was extremely high. Liver cirrhosis was present on percutaneous needle biopsy 9 months before she succumbed in progressive liver failure. Episodes of repeated gastrointestinal, life-threatening hemorrhages occurred during the last 6 months of her life. Histopathologic findings of the eyes were documented at autopsy. PMID- 1309210 TI - Staging designation for bilateral Wilms' tumors. PMID- 1309212 TI - The treatment of lower extremity sarcomas with wide excision, radiotherapy, and free-flap reconstruction. AB - Treatment of extremity sarcomas has evolved into a multidisciplinary approach utilizing surgery, radiotherapy, and, in some cases, chemotherapy. Limb-sparing surgery has maintained low rates of local recurrence when supplemented with early postoperative radiotherapy (brachytherapy). Leg defects that result from resection resemble those caused by trauma and appear ideally suited to free-flap reconstruction. However, the resection site is subjected to 4500 cGy of radiation given within 2 weeks of surgery. It has not been demonstrated that free flaps can endure early postoperative radiation without adverse effects. Three patients are presented with locally recurrent leg sarcomas treated by wide excision, brachytherapy, and free-flap reconstruction. All flaps survived, and the wounds healed uneventfully. This study reviews the current multidisciplinary approach to the treatment of lower extremity sarcomas and demonstrates the durability of free flap reconstruction in the presence of early postoperative radiation therapy. PMID- 1309211 TI - Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. AB - BACKGROUND: Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons. METHODS: We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide. RESULTS: Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis. CONCLUSIONS: Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence. PMID- 1309213 TI - Imaging of nephroblastomatosis: an overview. AB - Nephroblastomatosis is an abnormality of nephrogenesis characterized by incomplete maturation of primitive nephrogenic cells. The resultant individual lesions have variable histologic findings and distribution in the kidney. There is wide acceptance of nephroblastomatosis as a precursor lesion to Wilms tumor. Consequently, the role of imaging in assessing patients for neoplastic transformation of nephroblastomatosis should be emphasized. Computed tomography (CT) has been shown to be superior to ultrasound (US) in this regard. Nonetheless, the low cost and lack of radiation of US make it attractive for serial screening studies. Although magnetic resonance imaging shows promise in assessment of the kidney for nephrogenic rests, experience is limited in its use in evaluating patients for nephroblastomatosis. The authors present protocols for assessing patients identified as being at either high or low risk for the development of Wilms tumor due to nephroblastomatosis. These protocols take into account the advantages of CT and US. Scanning intervals are determined from epidemiologic data on the occurrence of Wilms tumor; the most intense screening occurs during the younger ages of life, when the likelihood of Wilms tumor development is highest. PMID- 1309214 TI - Hepatocellular carcinoma: reduced frequency of typical findings with dynamic contrast-enhanced CT in a non-Asian population. AB - Four computed tomographic (CT) findings have been described as typical or diagnostic of hepatocellular carcinoma: Primary morphologic findings include tumor encapsulation and fatty metamorphosis and secondary findings include venous invasion and arterioportal shunting. However, virtually all of the articles reporting these findings with significant frequency have been from Japan and thus represent an almost purely Asian population. The authors analyzed a series of 93 patients with hepatocellular carcinoma, only eight of whom were Asian. With the exception of venous invasion (48%), the analysis showed that while the four CT features may be typical of hepatocellular carcinoma, three features occurred with low frequency in a non-Asian population: tumor encapsulation, 12%; fatty metamorphosis, 0%; and arterioportal shunting, 4%. In addition, a review of the literature showed that all of the findings have occurred in other hepatic neoplasms, including benign and metastatic tumors. PMID- 1309215 TI - Hepatocellular carcinoma: evaluation with color Doppler US and MR imaging. AB - Fifteen patients with hepatocellular carcinoma underwent examination with color Doppler ultrasound (US), magnetic resonance (MR) imaging, dynamic computed tomography (CT), and angiography. Doppler signals ranging from 0.22 to 3.48 kHz could be obtained from within the tumor in 14 of 15 patients. The resistive index was 0.38-0.77. Color Doppler signals were visualized in nine of 15 lesions with a Doppler shift greater than 0.7 kHz. The Doppler signals and the resistive index of the tumor vessels became lower as the vessels progressed into the center of the lesion. The appearance of tumor vessels recognized on MR images obtained with gradient-recalled acquisition in the steady state (GRASS) in 11 of 15 lesions was compared with that on CT scans and angiograms. Tumors that were hyperintense on GRASS images obtained with a flip angle of 15 degrees transmitted Doppler signals of considerably higher amplitude compared with the isointense lesions. Both color Doppler US and MR imaging provided useful information for characterizing intratumoral blood flow. PMID- 1309216 TI - Small hepatocellular carcinoma: diagnosis with US angiography with intraarterial CO2 microbubbles. AB - Ultrasonographic (US) angiography enhanced with intraarterial CO2 microbubbles, a contrast material used in US imaging, was performed of 103 histologically proved hepatocellular carcinomas (HCCs) smaller than 3 cm in diameter in 95 patients. The detection rate for hypervascular HCC with US angiography was compared with the rate of detection with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil. Sensitivity in detection of hypervascular HCCs with US angiography was 86% (89 of 103 HCCs), compared with 63% (44 of 70 HCCs) detected with conventional angiography, 70% (23 of 33 HCCs) with DSA, and 82% (75 of 91 HCCs) with CT with iodized oil. US angiography depicted small hypervascular HCCs, especially those less than 1 cm in diameter, and helped clarify vascularity as isovascular or hypovascular in angiographically undetectable HCCs. Findings at US angiography assisted the choice of a therapeutic strategy for treatment of HCC, such as transarterial therapy, percutaneous ethanol injection therapy, or resection. PMID- 1309217 TI - Small hepatocellular carcinoma: differentiation from adenomatous hyperplastic nodule with color Doppler flow imaging. AB - Liver nodules smaller than 25 mm in diameter (19 hepatocellular carcinomas [HCCs] and nine adenomatous hyperplastic nodules [AHNs]) were examined with color Doppler flow imaging and hepatic angiography. Angiography revealed a tumor vessel in eight (42%) of the 19 HCCs, while color Doppler flow imaging revealed an arterial pulsating afferent tumor vessel in 10 (53%) of the 19 HCCs but in none of the AHNs. In addition, color Doppler flow imaging revealed a constant-flow efferent tumor vessel continuing to a portal branch in 10 (53%) of the 19 HCCs but in none of the AHNs. In 15 (79%) of the 19 HCCs, a pulsating afferent tumor vessel or a constant-flow efferent tumor vessel or both were observed. Therefore, in this series, color Doppler flow imaging was of value in distinguishing between these two lesions. PMID- 1309218 TI - Focal liver lesions: MR imaging with Mn-DPDP--initial clinical results in 40 patients. AB - Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate) (DPDP) was evaluated as a contrast agent for magnetic resonance (MR) imaging (1.5 T) of focal liver lesions in 40 patients. Doses of 5 and 10 mumol/kg were administered intravenously. Mn-DPDP-enhanced T1-weighted images were compared quantitatively and subjectively with standard T1- and T2-weighted nonenhanced images. Use of Mn-DPDP resulted in a statistically significant increase in signal intensity of liver parenchyma in T1-weighted images at both doses. No enhancement was seen in metastases, cholangiocarcinomas, or lymphomas, while all hepatocellular carcinomas were enhanced. Enhancement was seen in focal nodular hyperplasia and in regenerative nodules. The lesion-to-liver contrast in Mn-DPDP enhanced gradient-recalled-echo images was superior to that of all precontrast images (P less than .01). The number of nonenhancing malignant liver lesions detected in spin-echo (SE) images was increased (272 in T2-weighted SE images vs 390 in T1-weighted Mn-DPDP-enhanced SE images). Image interpretation (eg, visualization and demarcation of the lesions) was markedly better in Mn-DPDP enhanced images than in all precontrast images (P less than .001). PMID- 1309219 TI - Use of hot-tip laser probes to recanalize occluded expandable metallic biliary endoprostheses. PMID- 1309220 TI - Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors. AB - Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions. PMID- 1309221 TI - Intrahepatic cholangiocarcinoma: MR appearance. PMID- 1309222 TI - Energy-dependent processes involved in reduced drug accumulation in multidrug resistant human lung cancer cell lines without P-glycoprotein expression. AB - Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of [14C]daunorubicin was 30 and 12%, respectively, of that in the parent cells. When cells, at steady state, were permeabilized with digitonin, the amount of daunorubicin binding increased only in the resistant cells. The reduced accumulation of daunorubicin in the SW 1573/2R120 and GLC4/ADR cells was accompanied by a lower initial (2 min) uptake rate of this drug. No difference in initial efflux rate of daunorubicin from preloaded cells could be detected between sensitive and resistant SW-1573 cells. However, daunorubicin was extruded 5-fold faster from GLC4/ADR cells than from the parental cells. In the presence of the energy metabolism inhibitors sodium azide and deoxyglucose, the reduced daunorubicin accumulations in the SW 1573/2R120 and GLC4/ADR MDR cells were (almost) completely reversed. The effects of these inhibitors on drug uptake were already apparent during the earliest measured time points (less than 15 s). Also, the enhanced efflux of daunorubicin from GLC4/ADR cells was inhibited. In ATP-depleted cells, the intracellular pH was lowered by approximately 0.3 units in resistant as well as in sensitive cells. The lower intracellular pH, however, could not account for the increase in daunorubicin accumulation in the resistant cells. Also, for vincristine and etoposide, the increases in drug accumulation under energy-deprived conditions were more pronounced in the resistant SW-1573/2R120 cells than in the parent SW 1573 cells. These results suggest that accumulation of drugs in the non-P glycoprotein MDR human lung carcinoma cell lines SW-1573/2R120 and GLC4/ADR is reduced by an energy-dependent drug export mechanism which prevents efficient transport of drug to the target. Since P-glycoprotein expression in lung tumors is generally low, these MDR lung cancer cell lines can be used as a model to study alternative mechanisms leading to multidrug resistance in this tumor type. PMID- 1309223 TI - ras transformation of simian virus 40-immortalized rat hepatocytes: an in vitro model of hepatocarcinogenesis. AB - Primary rat hepatocytes were transfected with simian virus 40 DNA and cultured in a chemically defined medium. Proliferating colonies developed after 2-3 weeks. Three cell lines were established by cloning albumin-secreting colonies, as identified by an immunooverlay assay. Two of the cell lines, ALB-6 and ALB-8, expressed all five liver-specific mRNAs studied, albumin, alpha-1-antitrypsin, fibrinogen, alpha-1-acid glycoprotein, and histidase. ALB-6 cells were nontumorigenic in nude mice while ALB-8 cells were weakly tumorigenic with only one of four injected nude mice developing a slowly growing tumor. Further transfection of ALB-6 and ALB-8 cells with an activated c-Ha-ras or N-ras oncogene resulted in strongly tumorigenic cells. The tumors induced by ras transformed ALB-6 cells were moderately differentiated hepatocellular carcinomas. The tumors derived from ras-transformed ALB-8 cells were poorly differentiated, while the slowly growing tumors induced by untransfected or control DNA transfected ALB-8 cells were well-differentiated trabecular hepatocellular carcinomas, suggesting histological dedifferentiation of cells following ras transformation. However, the synthetic capabilities of the cells were not lost in that the ras-transfected cultures and the tumors induced by ras-transformed cells retained the ability to synthesize the five liver-specific mRNAs. Thus we have developed an in vitro model of carcinogenesis in which, by sequential exposure to SV40 DNA and a ras oncogene, primary rat hepatocytes are transformed. PMID- 1309224 TI - Relative activity of structural analogues of amsacrine against human leukemia cell lines containing amsacrine-sensitive or -resistant forms of topoisomerase II: use of computer simulations in new drug development. AB - Anilino analogues of amsacrine showed increased activity against amsacrine (AMSA) resistant cell lines when compared with the parent compound, but the mechanisms of amsacrine resistance in these lines were unknown (Finlay, G. J., Baguley, B. C., Snow, K., and Judd, W., J. Natl. Cancer Inst., 82: 662-667, 1990). We tested the cytotoxic and DNA-cleaving activities of two amsacrine analogues which were derivatives of 9-anilinoacridine (1'-methylcarbamate and 1'-benzenesulfonamide) against an amsacrine-resistant human leukemia cell line (HL-60/AMSA) whose resistance is due to an amsacrine-resistant topoisomerase II. Neither agent could overcome the amsacrine resistance of HL-60/AMSA. Neither agent could induce HL 60/AMSA topoisomerase II-mediated cleavage of DNA in an isolated biochemical system, although at high concentrations the two analogues could inhibit HL 60/AMSA topoisomerase II-mediated DNA strand passage. Both analogues were at least as active, if not more active, than amsacrine against amsacrine-sensitive HL-60 and its topoisomerase II. Comparison of the cellular and biochemical results with those from computer simulation of the energy-minimized structures of amsacrine, its inactive isomer o-AMSA, and the two new active analogues suggests the following possibilities: (a) the positioning of the potential topoisomerase II-binding site (1'-anilino group) of the two new drugs resembles the positioning of this site in amsacrine; (b) the HL-60 topoisomerase II has a binding site which interacts with amsacrine and the two anilino analogues but not with o-AMSA, an analogue with altered positioning of the methoxy group; (c) the HL-60/AMSA topoisomerase II interacts with reduced affinity with amsacrine and the two anilino analogues, although HL-60/AMSA topoisomerase II still interacts with the structurally distinct topoisomerase II-reactive nonintercalator, etoposide; (d) because of their higher DNA binding affinity or the greater possible positions of their side groups in comparison to amsacrine, the two analogues can, at high concentrations, inhibit the strand-passing activity of HL-60/AMSA topoisomerase II. PMID- 1309225 TI - Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo. AB - Many cancer cell lines express basic fibroblast growth factor (FGF) receptors, making them potential targets for the delivery of FGF-based cytotoxic compounds. To this end, we have investigated the antitumor activity of a novel mitotoxin, Fibroblast Growth Factor-saporin (FGF-SAP), a conjugate of FGF and the ribosome inactivating protein, saporin. In vitro, FGF-SAP is cytotoxic for human melanoma, teratocarcinoma, and neuroblastoma cells expressing FGF-receptors. Mice treated with FGF-SAP i.v., on a variety of schedules, showed dramatic tumor growth inhibition with minimal toxicity. Thus, FGF-SAP appears to be a well-tolerated and potent antitumor agent. The potential of FGF-targeted cytotoxicity is discussed. PMID- 1309226 TI - Topoisomerase II alpha and topoisomerase II beta genes: characterization and mapping to human chromosomes 17 and 3, respectively. AB - Human cells contain two topoisomerase II isozymes named topo II alpha and topo II beta. The complementary DNAs for both enzymes have been cloned. The topo II alpha and topo II beta complementary DNAs hybridized to unique sequences of human, rodent, and chicken DNAs in Southern blots. The human topo II alpha gene has previously been mapped to chromosome 17. We confirmed the chromosomal location of topo II alpha and mapped the topo II beta gene to chromosome 3. In addition, topo II beta exhibits genetic polymorphism as has been reported for topoisomerases I and II alpha. PMID- 1309227 TI - Neuropeptide signal transduction in lung cancer: clinical implications of bradykinin sensitivity and overall heterogeneity. AB - To define the role of neuropeptides in lung cancer biology, we evaluated the effect of seven peptide classes on signal transduction and growth in human lung and breast cancer cell lines. Flow cytometric methods were used to quantitate the calcium response in individual cells produced by these peptides alone or in combination. The effects on growth were assessed by [3H]thymidine, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and soft agarose colony assays. All lung cancer cells demonstrated calcium responses to one or more peptides with classic small cell lines displaying the greatest responsiveness, followed by variant small cell lines and non-small cell lines. Breast cancer cell lines demonstrated little or no response. There was great variability in the magnitude of calcium response and pattern of response between lung cancer cell lines to individual neuropeptides. Bradykinin was the most potent peptide and produced responses in the highest fraction of lung cancer cell lines. Combinations of peptides produced greater intracellular calcium release than the single peptides, although in less than a quantitatively additive manner. Each peptide produced a refractory period which was peptide class specific. The growth stimulating effects of these neuropeptides were absent or small in magnitude and did not correlate with calcium signal transduction. These results imply that lung cancer cells display a wide sensitivity to neuropeptides but in a very heterogeneous manner. Knowledge of this heterogeneity should be incorporated into the design of antitumor strategies based on this autocrine pathway. PMID- 1309228 TI - High levels of enhanced reactivation of herpes simplex virus in skin fibroblasts from various hereditary cancer-prone syndromes. AB - The dose response of the enhanced reactivation (ER) of herpes simplex virus type 1 has been studied in UV-irradiated normal human skin fibroblasts and fibroblasts from the following hereditary cancer-prone syndromes: retinoblastoma, aniridia, polyposis coli, neurofibromatosis type 1 and 2, dysplastic nevus syndrome, Von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, and Bloom's syndrome. Surprisingly, much higher levels of ER were observed in all these genetically heterogeneous hereditary disorders than in normal human skin fibroblasts. These results suggest that loss of one allele of putative tumor suppressor genes may activate cellular processes that result in the induction of the ER response, and they support our previous observation suggesting that ER may somehow be related to the process of carcinogenesis (P. J. Abrahams et al., Cancer Res., 48: 6054-6057, 1988). PMID- 1309229 TI - Measurement of SO2 effects on the 218Po ion mobility spectrum by alpha-track detection. AB - A number of investigators have reported the formation of radiolytic ultrafine particles produced by the interaction of ionizing radiation with atmospheric trace gases. Previous studies have suggested that a very high localized concentration of the OH radical produced by the radiolysis of water can react with atmospheric trace gas, like SO2, to produce lower vapor pressure compounds that can then nucleate. To determine trace-gas dependence of the active, positively charged, first decay product of radon, the mobility spectrum of the decay products in the range of 0.06-3.0 cm2 V-1s-1 was measured in a flow-through radon chamber using a specially designed mobility spectrometer. Measurements were taken for different relative humidities and concentrations of SO2 in purified laboratory compressed air. The resultant mobility spectra were compared with radiolytic ultrafine particle activity distribution data. In the case of low humidities, the reduction of available OH concentration and hence neutralization rate led to the increasing intensity of the shoulder around 1.35 cm2 V-1s-1 with increasing SO2, suggesting SO2 clustering around the PoOx+ ion. For high humidity conditions (5 ppm SO2, 30% RH), there was clear droplet formation, H2SO4, clustering around the ion, and also an increase in the background level between the high mobility peak and droplet peak. PMID- 1309230 TI - Increased cerebrospinal fluid dopamine and 3,4-dihydroxyphenylacetic acid levels in Huntington's disease: evidence for an overactive dopaminergic brain transmission. AB - Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5 hydroxyindoleacetic acid (5-HIAA) in the CSF of patients with Huntington's disease (HD) were measured by HPLC. CSF DA, DOPAC, and MHPG levels were found to be increased in HD patients. Levels of HVA, 5-HIAA, and NA in the CSF of HD patients did not differ from those of controls. Changes in CSF DA and DOPAC levels were consistent with previous findings of increased DA tissue content in some brain areas of patients with HD. These results suggest that CSF DOPAC levels could be a more reliable index of overactive dopaminergic brain systems in HD than CSF HVA levels. PMID- 1309231 TI - Terminal autoreceptor control of 5-hydroxytryptamine release as measured by in vivo microdialysis in the conscious guinea-pig. AB - In vivo microdialysis in the frontal cortex of the freely moving guinea-pig was used to measure extracellular 5-hydroxytryptamine (5-HT) and study terminal autoreceptor control of its release. The indoleamine levels were determined by HPLC with electrochemical detection. Release of extracellular 5-HT and, to a lesser extent, 5-hydroxyindoleacetic acid was sensitive to tetrodotoxin, confirming the neuronal origin of measured neurotransmitter levels. Both systemic and local administration of the 5-HT1 agonist 5-carboxamidotryptamine caused inhibition of extracellular 5-HT levels, confirming the regulatory role of the terminal, and possibly also the somatodendritic, 5-HT autoreceptor on neuronal 5 HT release. Levels of extracellular 5-hydroxyindoleacetic acid were not affected by 5-carboxamidotryptamine following either central or peripheral administration. PMID- 1309233 TI - Inositol lipids and signal transduction in the nervous system: an update. PMID- 1309232 TI - Differential responses of the phosphorylation of ribosomal protein S6 to nerve growth factor and epidermal growth factor in PC12 cells. AB - Previous studies from this laboratory have shown that the phosphorylation of the S6 protein of the ribosomes is catalyzed by at least two different and separable kinase activities in PC12 cells. One of these activities is increased by treatment of the cells with nerve growth factor, the other by treatment of the cells with epidermal growth factor. The present work shows that these two factors stimulate the phosphorylation of S6 with quite different kinetics, and that both the number of phosphates incorporated into S6 and the phosphopeptide pattern of S6 are different in cells treated with nerve growth factor than in cells treated with epidermal growth factor. The characteristics of the nerve growth factor sensitive S6 kinase and of the epidermal growth factor-sensitive kinase were also clearly different. Substrate specificity and inhibitor studies indicated that neither was identical to cyclic AMP-dependent kinase, kinase C, or the calcium/calmodulin-dependent kinases. However, two major phosphopeptides produced by S6 phosphorylation in nerve growth factor-treated cells were also seen on phosphorylation of S6 by cyclic AMP-dependent kinase in vitro. In addition, when rat liver 40S ribosomal subunits were pretreated with cyclic AMP-dependent kinase in vitro, the action of the nerve growth factor-sensitive S6 kinase was increased about twofold. PMID- 1309234 TI - Human brain lectin: a soluble lectin that binds actin. AB - A biotinylated probe was used for detection of endogenous ligands of a human brain lectin on blotted human brain soluble proteins. Of the various proteins from brain extract resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, five reacted with the biotinylated probe. After elimination of saccharidic moieties by periodic treatment of the same extract, a single band with Mr approximately 43,000 was recognized by the lectin. This band was identified as actin using an anti-actin antibody. These results were confirmed by binding of biotinylated lectin to purified actin. PMID- 1309235 TI - Forskolin stimulation of cyclic AMP accumulation in rat brain cortex slices is markedly enhanced by endogenous adenosine. AB - Stimulation of cyclic AMP (cAMP) accumulation in rat cortex slices by 1 microM forskolin (F) was markedly reduced (96%) by treatment with adenosine deaminase (ADA). The effect of ADA was progressively less at higher concentrations of F, but still inhibited the response by 50% at 100 microM F. ADA-mediated inhibition of the cAMP response to 1 microM F was completely reversed by 5 microM 2 chloroadenosine (CA), an ADA-resistant analogue. Stimulation by F (controls) and F plus CA (ADA treated) in cortex slices was significantly inhibited by 200 microM caffeine (CAF) and by 10 microM 8-phenyltheophylline. cAMP accumulation in ADA-treated cortex slices stimulated with CA at concentrations from 5 to 100 microM was markedly enhanced by 1 microM F. Neither ADA treatment nor 200 microM CAF significantly affected cAMP accumulation in slices stimulated by 1 microM vasoactive intestinal polypeptide or adenylate cyclase in membranes stimulated by 1 microM F. CAF (1 mM) did not significantly increase basal cAMP levels in cortex slices, whereas 1 mM 3-isobutyl-1-methylxanthine caused a significant 80% increase and 100 microM rolipram enhanced cAMP levels by 4.5-fold. F-stimulated cAMP accumulation (1 microM) in cortex slices was inhibited 98% by 1 mM CAF and 49% by 1 mM 3-isobutyl-1-methylxanthine, and was enhanced 2.5-fold by 100 microM rolipram. These data have been interpreted to indicate that the stimulation of cAMP accumulation in rat cortex slices by 1 microM F is predominantly due to synergistic interaction with endogenous adenosine and that the inhibition of this response by CAF is largely due to blockade of adenosine receptors. PMID- 1309236 TI - Expression of functional bradykinin receptors in Xenopus oocytes. AB - mRNA prepared from various tissues and cultured cells was injected into Xenopus laevis oocytes. Three to five days after injection, the response of the oocytes to the peptide bradykinin was monitored. The oocytes were voltage clamped and the membrane currents generated on application of agonist were recorded. mRNA from NG108-15, rat uterus, and human fibroblast cell line WI38 gave similar responses to bradykinin (1 microM), with an initial inward current (10-20 nA) followed by a prolonged period of membrane current oscillations. The same pattern of response was given by total RNA from rat dorsal root ganglia. No response to bradykinin (10 microM) was recorded from oocytes injected with rat brain mRNA, although these oocytes gave peak inward currents of about 75 nA in response to serotonin (10 microM). mRNA from both NG108-15 cells and rat uterus was fractionated on sucrose gradients. This resulted in an approximately five-fold increase in the size of the response compared to that given by unfractionated mRNA. The largest responses were given by mRNA fractions with a size of approximately 4.5 kb. Data were obtained consistent with the expression of both B1 and B2 receptors by WI38 human fibroblasts and with the expression of only the B2 type of receptor by NG108-15 cells. PMID- 1309237 TI - Lithium effects on inositol phospholipids and inositol phosphates: evaluation of an in vivo model for assessing polyphosphoinositide turnover in brain. AB - Administration of lithium chloride to rats injected intracerebrally with [3H]inositol led to time- and dose-dependent increases in levels of labeled inositol monophosphates in brain. Quantitative analysis of the inositol phosphates by ion chromatography revealed 37- and 20-fold increases in the mass of myo-inositol 1-phosphate and 4-phosphate, respectively, at 4 h intraperitoneal after injections of 6 mEq/kg of lithium chloride. Albeit to a much lesser extent, lithium administration also resulted in an increase in the level of myo-inositol, 1,4-bisphosphate in brain. The lithium-induced increase in content of labeled inositol monophosphates was marked by a concomitant decrease in content of labeled inositol, and after injections of high doses of lithium, e.g., 10 mEq/kg, this was followed by a general decrease in labeling of the inositol phospholipids. In general, animals injected with [3H]inositol but not lithium did not reveal obvious differences in labeling of inositol monophosphates on stimulation by mecamylamine or pilocarpine. However, when animals were injected with [3H]inositol and then lithium, there were large increases in the levels of labeled inositol monophosphates on administration of these compounds. Administration of atropine to the lithium-treated mice led to a partial reduction in the amount of labeled inositol monophosphates accumulated due to the administration of lithium alone. Furthermore, atropine was able to block the pilocarpine-induced increase in level of labeled inositol monophosphates. These results demonstrate the suitable use of the radiotracer technique together with lithium administration for assessing the effects of drugs and receptor agonists on the signaling system involving polyphosphoinositide turnover in brain. PMID- 1309238 TI - Characterization of [3H]Ro 5-4864 binding sites in rat vas deferens. AB - The presence of benzodiazepine binding sites in rat vas deferens was detected using [3H]Ro 5-4864 as a radioligand. The binding of [3H]Ro 5-4864 to the mitochondrial sites is saturable, reversible, and temperature and time dependent. The association rate constant (k1) was 8.7 +/- 0.7 x 10(7) M-1 min-1, and the dissociation rate constant (k-1) was 0.031 +/- 0.003 min-1. The dissociation constant (KD) determined by saturation binding was 5.22 +/- 0.56 nM. The density of binding was 4,926 +/- 565 fmol/mg of protein. The Hill coefficient of binding was 0.99 +/- 0.01, an indication that [3H]Ro 5-4864 binds to a single site. The [3H]Ro 5-4864 binding was inhibited competitively by Ro 5-4864 and 2-hydroxy-5 nitrobenzyl-6-thioguanosine and noncompetitively by PK 11195, nitrendipine, alpha,beta-methylene-ATP, and carboxyatractyloside and was not affected by clonazepam, dicyclohexylcarbodiimide, or protoporphyrin IX. Our data indicate that [3H]Ro 5-4864 binding sites are not identical to those labeled by PK 11195. These binding sites are modulated by the ADP/ATP mitochondrial carrier, and an interaction of dihydropyridines and [3H]Ro 5-4864 binding sites in rat vas deferens is suggested. PMID- 1309239 TI - The epithelial phenotype of human neuroblastoma cells express bradykinin, endothelin, and angiotensin II receptors that stimulate phosphoinositide hydrolysis. AB - The neuroblastoma line SK-N-SH consists of distinct and interconverting cell types, which include a neuroblast phenotype (SH-SY5Y), an epithelial phenotype (SH-EP), and an intermediate cell type (SH-IN). In SH-SY5Y cells, only muscarinic receptor activation produced stimulation of phosphoinositide turnover, whereas in SH-EP cells, where muscarinic receptors are not present, the peptides bradykinin, endothelin, and angiotensin II stimulated phosphoinositide hydrolysis with EC50 values of 16, 6, and 0.7 nM, respectively, and a rank order of maximal effects of bradykinin greater than endothelin greater than angiotensin II. Fetal calf serum at concentrations between 1 and 10% was also a potent stimulator of phosphoinositide hydrolysis in SH-EP cells but not in SH-SY5Y cells. In the intermediate cell clone, SH-IN, phosphoinositide hydrolysis was stimulated not only by muscarinic receptors, but also by endothelin, bradykinin, and serum, an indication that this cell type harbors all the kinds of receptors that are differentially expressed in the other two cell types. The effects of the three peptides--bradykinin, endothelin, and angiotensin II--on phosphoinositide hydrolysis in SH-EP cells were additive, a result suggesting that the three kinds of receptors may activate distinct transducer proteins and/or phospholipase C subtypes. Pretreatment of intact SH-EP cells with pertussis toxin under conditions sufficient to ADP-ribosylate 90-95% of the endogenous guanine nucleotide regulatory protein substrates did not impair the ability of any of the receptors to stimulate phosphoinositide hydrolysis in any of the cell types. In contrast, short-term exposure to the phorbol ester 12-O-tetradecanoylphorbol 13 acetate (1 microM) abolished the stimulation of phosphoinositide hydrolysis mediated by peptide receptors in SH-EP cells and partially inhibited that by muscarinic receptors in SH-SY5Y cells. Prolonged incubation of SH-EP cells with phorbol ester resulted in a recovery of receptor responsiveness, the extent and rate of which were different for each receptor type. In contrast, there was no recovery of responsiveness for muscarinic receptors in SH-SY5Y cells. The pattern of phorbol ester-mediated effects depended on the cell rather than on the receptor type. In fact, muscarinic receptor responsiveness in SH-IN, the intermediate cell type, was desensitized by and recovered from treatment with phorbol esters in a manner more similar to peptide receptors in SH-EP than to muscarinic receptors in SH-SY5Y. These data suggest that the transduction mechanisms by which distinct receptor types are coupled to phosphoinositide hydrolysis in the three cell phenotypes differ in sensitivity to feedback regulation by protein kinase C. PMID- 1309240 TI - Quantitative immunoprecipitation studies with anti-gamma-aminobutyric acidA receptor gamma 2 1-15 Cys antibodies. AB - Antibodies raised against the synthetic peptide NH2-QKSDDDYEDYASNKTC-COOH (gamma 2 1-15 Cys), which corresponds to the N-terminal amino acid sequence with a C terminal cysteine of the human gamma 2 subunit of the gamma-aminobutyric acidA (GABAA) receptor, were used to study the quantitative immunoprecipitation of agonist benzodiazepine binding sites from bovine brain. Anti-gamma 2 1-15 Cys antibodies were found to immunoprecipitate specifically in parallel [3H]flunitrazepam- and [3H]muscimol-reversible binding sites in a dose-dependent manner. The maximum percentages of [3H]flunitrazepam binding sites immunoprecipitated from detergent extracts of bovine cerebral cortex, cerebellum, and hippocampus were 68, 77, and 83%, respectively. Immunoprecipitation studies with anti-alpha 1 324-341 antibodies carried out in parallel with anti-gamma 2 1 15 Cys antibodies provided evidence for the promiscuity of the gamma 2 subunit within native GABAA receptors. These results substantiate the association of the gamma 2 polypeptide with native GABAA receptors. PMID- 1309241 TI - Hydroxylapatite block closure of oroantral fistulas: report of cases. PMID- 1309242 TI - Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. AB - Previous studies on Epstein-Barr virus (EBV)-positive B-cell lines have identified two distinct forms of virus latency. Lymphoblastoid cell lines generated by virus-induced transformation of normal B cells in vitro, express the full spectrum of six EBNAs and three latent membrane proteins (LMP1, LMP2A, and LMP2B); furthermore, these lines often contain a small fraction of cells spontaneously entering the lytic cycle. In contrast, Burkitt's lymphoma-derived cell lines retaining the tumor biopsy cell phenotype express only one of the latent proteins, the nuclear antigen EBNA1; such cells do not enter the lytic cycle spontaneously but may be induced to do so by treatment with such agents as tetradecanoyl phorbol acetate and anti-immunoglobulin. The present study set out to determine whether activation of full virus latent-gene expression was a necessary accompaniment to induction of the lytic cycle in Burkitt's lymphoma lines. Detailed analysis of Burkitt's lymphoma lines responding to anti immunoglobulin treatment revealed three response pathways of EBV gene activation from EBNA1-positive latency. A first, rapid response pathway involves direct entry of cells into the lytic cycle without broadening of the pattern of latent gene expression; thereafter, the three "latent" LMPs are expressed as early lytic cycle antigens. A second, delayed response pathway in another cell subpopulation involves the activation of full latent gene expression and conversion to a lymphoblastoidlike cell phenotype. A third response pathway in yet another subpopulation involves the selective activation of LMPs, with no induction of the lytic cycle and with EBNA expression still restricted to EBNA1; this type of latent infection in B lymphocytes has hitherto not been described. Interestingly, the EBNA1+ LMP+ cells displayed some but not all of the phenotypic changes normally induced by LMP1 expression in a B-cell environment. These studies highlight the existence of four different types of EBV infection in B cells, including three distinct forms of latency, which we now term latency I, latency II, and latency III. PMID- 1309243 TI - Induction of erythropoietin responsiveness in murine hematopoietic cells by the gag-myb-ets-containing ME26 virus. AB - ME26 virus, which was generated by inserting the coding region of the acute avian leukemia-inducing virus E26 into a murine retrovirus vector, encodes a 135-kDa gag-myb-ets fusion protein. Amphotropic murine leukemia virus pseudotypes of ME26 virus induce a high incidence of erythroleukemia 2 to 4 months after injection into newborn NFS/N mice. Spleen cells from the majority of these mice proliferate to high levels in the presence of the erythroid hormone erythropoietin (Epo) and can easily be established as permanent Epo-dependent cell lines. The cell lines contain multiple copies of ME26 viral DNA and express viral message and protein. An Epo receptor mRNA of normal size can be detected in these cells, and binding studies reveal a single class of lower-affinity Epo receptor with an affinity for Epo that is in the range of that previously reported for erythroid cells. The ME26 virus-induced Epo-dependent cell lines, however, appear more immature than previously described erythroid cell lines and more closely resemble early hematopoietic precursor cells, suggesting that the virus may be activating the Epo receptor in hematopoietic cells that do not normally express it. Consistent with this idea, we are able to infect an interleukin-3-dependent myeloid cell line, FDC-P2, with ME26 virus and convert it to Epo dependence. The ME26 virus infected FDC-P2 cells, even before growth on Epo, showed a large increase in the amount of Epo receptor mRNA. However, no ME26 viral integrations can be detected adjacent to the Epo receptor gene, indicating that the virus is not activating the Epo receptor gene by promoter/enhancer insertion. Our results are more consistent with the hypothesis that the gag-myb-ets-encoded viral fusion protein, which is known to bind DNA, is directly or indirectly activating the expression of the Epo receptor gene in these cells. PMID- 1309244 TI - cis-acting regulatory regions in the long terminal repeat of simian foamy virus type 1. AB - Simian foamy virus type 1 (SFV-1), a member of the Spumavirinae subfamily of retroviruses, encodes a transcriptional transactivator (taf) that strongly augments gene expression directed by the viral long terminal repeat (LTR) (A. Mergia, K. E. S. Shaw, E. Pratt-Lowe, P. A. Barry, and P. A. Luciw, J. Virol. 65:2903-2909, 1991). This report describes cis-acting regulatory elements in the LTR that control viral gene expression. A series of LTR mutants and hybrid promoter constructs have been analyzed in transient expression assays for responsiveness to Taf. The targets for transactivation have been mapped to two regions of the U3 domain of the LTR, between positions -1196 and -880 and between positions -403 and -125 (+1 represents the transcription initiation site). No significant nucleotide sequence homology between these two regions is noted; thus, the SFV-1 taf gene acts through at least two distinct sequence elements in the LTR. The target contained between positions -403 and -125 acts independently of orientation, in different cell types and species, and in the context of a heterologous promoter. Thus, the target element between positions -403 and -125 has properties of a transcriptional enhancer. The observation that two distinct elements in the SFV-1 LTR are targets for transcriptional transactivation is novel with respect to observations for other retroviral systems. The R-U5 region of the SFV-1 LTR down-regulates transactivation by severalfold. Computer analysis of the R-U5 region revealed a secondary structure with a free-energy level of -74 kcal (ca. -310,000 J); this structural feature may account for the inhibitory effect on gene expression directed by the LTR. Taf of SFV-1 had no effect on gene expression directed by the LTR of the related human foamy virus, whereas Taf transactivates gene expression directed by the LTRs of the human and simian immunodeficiency viruses. Comparative functional analysis of Taf on homologous and heterologous LTRs may facilitate elucidation of the mechanism of transactivation of foamy viruses. PMID- 1309245 TI - Deletion of the VP16 open reading frame of herpes simplex virus type 1. AB - VP16 (also called Vmw65 and alpha TIF) is a structural protein of herpes simplex virus type 1 (HSV-1) that trans-induces HSV-1 immediate-early gene transcription. This report describes an HSV-1 VP16 deletion mutant that was constructed and propagated in a cell line transformed with a VP16 expression vector. The VP16 deletion mutant replicated like wild-type HSV-1 during infection of the VP16 expressing cell line. Deletion mutant virions propagated in this cell line contained wild-type, cell-derived VP16 protein that was recruited during virion assembly and was functional for immediate-early gene trans-induction. The mutant failed to replicate during subsequent infection of cells that do not express VP16, as determined in plaque assays and single-step replication assays. The deletion mutant induced nearly normal levels of viral DNA synthesis and capsid production during these infections, but it induced slightly lower levels of viral DNA encapsidation and appeared by transmission electron microscopy to be defective in further steps of virion maturation. A genetic revertant of the deletion mutant that was restored for VP16-coding sequences exhibited fully wild type replication properties in both VP16-expressing and nonexpressing cells. The absence of VP16 protein synthesis at late times of HSV-1 infection prevents the production of infectious progeny virus and correlates with a profound defect in HSV-1 particle assembly. PMID- 1309246 TI - Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3. AB - We have previously defined ie3 as a coding region located downstream of the ie1 gene which gives rise to a 2.75-kb immediate-early (IE) transcript. Here we describe the structural organization of the ie3 gene, the amino acid sequence of the gene product, and some of the functional properties of the protein. The 2.75 kb ie3 mRNA is generated by splicing and is composed of four exons. The first three exons, of 300, 111, and 191 nucleotides (nt), are shared with the ie1 mRNA and are spliced to exon 5, which is located downstream of the fourth exon used by the ie1 mRNA. Exon 5 starts 28 nt downstream of the 3' end of the ie1 mRNA and has a length of 1,701 nt. The IE3 protein contains 611 amino acids, the first 99 of which are shared with the ie1 product pp89. The IE3 protein expressed at IE times has a relative mobility of 88 kDa in gels, and a mobility shift to 90 kDa during the early phase is indicative of posttranslational modification. Sequence comparison reveals significant homology of the exon 5-encoded amino acid sequence with the respective sequence of UL 122, a component of the IE1-IE2 complex of human cytomegalovirus (HCMV). This homology is also apparent at the functional level. The IE3 protein is a strong transcriptional activator of the murine cytomegalovirus (MCMV) e1 promoter and shows an autoregulatory function by repression of the MCMV ie1/ie3 promoter. The high degree of conservation between the MCMV ie3 and HCMV IE2 genes and their products with regard to gene structure, amino acid sequence, and protein functions suggests that these genes play a comparable role in the transcriptional control of the two cytomegaloviruses. PMID- 1309247 TI - Herpes simplex virus type 1 recombination: role of DNA replication and viral a sequences. AB - During the course of infection, elements of the herpes simplex virus type 1 (HSV 1) genome undergo inversion, a process that is believed to occur through the viral a sequences. To investigate the mechanism of this recombinational event, we have developed an assay that detects the deletion of DNA segments flanked by directly repeated a sequences in plasmids transiently maintained in Vero cells. With this assay, we have observed a high frequency of recombination (approximately 8%) in plasmids that undergo replication in HSV-1-infected cells. We also found a low level of recombination between a sequences in plasmids introduced into uninfected cells and in unreplicated plasmids in HSV-1-infected cells. In replicating plasmids, recombination between a sequences occurs at twice the frequency seen with directly repeated copies of a different sequence of similar size. Recombination between a sequences appears to occur at approximately the same time as replication, suggesting that the processes of replication and recombination are closely linked. PMID- 1309248 TI - Yeast cells are incapable of translating RNAs containing the poliovirus 5' untranslated region: evidence for a translational inhibitor. AB - We have expressed in the yeast Saccharomyces cerevisiae a full-length poliovirus cDNA clone under the control of the GAL10 promoter to better characterize the effect of poliovirus on host cell metabolism. We find that yeast cells are unable to translate poliovirus RNA in vivo and that this inhibition is mediated through the 5' untranslated region of the viral RNA. The in vivo inhibition of translation of poliovirus RNA and P2CAT RNA (which contains the 5' untranslated region fused upstream of the bacterial chloramphenicol transferase gene) can be mimicked in vitro in yeast translation lysates. In fact, a trans-acting inhibitor present in yeast lysates can inhibit translation of either poliovirus or P2CAT RNA in HeLa cell translation lysates. In contrast, when the inhibitor is added to translations programmed with chloramphenicol acetyltransferase RNA, yeast prepro alpha-factor RNA, or an RNA containing the internal ribosome entry site of encephalomyocarditis virus, no inhibition is seen. The inhibitory activity has been partially purified by DEAE-Sephacel chromatography. The partially purified inhibitor is heat stable, escapes phenol extraction, is resistant to proteinase K and DNase I treatment, and is sensitive to RNase A digestion, suggesting that the inhibitor is an RNA. In an in vitro translation assay, the inhibitory activity can be overcome by increasing the concentration of HeLa cell lysate but not P2CAT RNA, suggesting that the inhibitor interacts (directly or indirectly) with one or more components of the HeLa cell translational machinery rather than with the viral RNA. PMID- 1309249 TI - Transcriptional activation of several heterologous promoters by the E6 protein of human papillomavirus type 16. AB - The E6 protein of human papillomavirus type 16 (HPV-16), along with E7, is responsible for the HPV-induced malignant transformation of the cervix. However, the mechanism of this transformation activity is not well understood. We investigated whether the entire E6 protein of HPV-16 could act as an activator of transcription. Experiments in which NIH 3T3 cells were cotransfected with an E6 expression vector together with the reporter chloramphenicol acetyltransferase (CAT) gene linked to various minimal promoters indicated that E6 could activate transcription from a series of viral TATA-containing promoters. Mutations or deletions that affected all upstream regulatory elements present in the thymidine kinase (TK) promoter, such as the GC and CAAT boxes, reduced the level of E6 induced transcription. However, compared with the basal level, these truncated promoters were still activated by E6. Although site-directed mutations of the TATA sequence present in the TK or human immunodeficiency virus long terminal repeat promoters reduced the level of basal transcription, they did not abolish the E6-mediated activation. Moreover, E6 could restore almost completely the full level of wild-type E6-induced transcription as long as the upstream regulatory elements (GC/CAAT in the TK promoter, NF-kappa B in the human immunodeficiency virus long terminal repeat) were intact. This dual interaction of HPV-16 E6 is reminiscent of the activity of a coactivator. PMID- 1309250 TI - Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. AB - A mutant of herpes simplex virus type 1 (HSV-1) in which glycoprotein H (gH) coding sequences were deleted and replaced by the Escherichia coli lacZ gene under the control of the human cytomegalovirus IE-1 gene promoter was constructed. The mutant was propagated in Vero cells which contained multiple copies of the HSV-1 gH gene under the control of the HSV-1 gD promoter and which therefore provide gH in trans following HSV-1 infection. Phenotypically gH negative virions were obtained by a single growth cycle in Vero cells. These virions were noninfectious, as judged by plaque assay and by expression of beta galactosidase following high-multiplicity infection, but partial recovery of infectivity was achieved by using the fusogenic agent polyethylene glycol. Adsorption of gH-negative virions to cells blocked the adsorption of superinfecting wild-type virus, a result in contrast to that obtained with gD negative virions (D. C. Johnson and M. W. Ligas, J. Virol. 62:4605-4612, 1988). The simplest conclusion is that gH is required for membrane fusion but not for receptor binding, a conclusion consistent with the conservation of gH in all herpesviruses. PMID- 1309251 TI - Subunit interactions of vesicular stomatitis virus envelope glycoprotein stabilized by binding to viral matrix protein. AB - The mechanism by which viral glycoproteins are incorporated into virus envelopes during budding from host membranes is a major question of virus assembly. Evidence is presented here that the envelope glycoprotein (G protein) of vesicular stomatitis virus binds to the viral matrix protein (M protein) in vitro with the specificity, reversibility, and affinity necessary to account for virus assembly in vivo. The assay for the interaction is based on the ability of M protein to stabilize the interaction of G protein subunits, which exist as trimers of identical subunits in the virus envelope. The interaction with M protein was shown by using G proteins labeled with fluorescent probes capable of detecting subunit dissociation and reassociation in vitro. The results show that the M protein isolated from virions either as purified soluble protein or as nucleocapsid-M protein complexes interacts with the G protein in vitro and that the reaction is reversible. The interaction between the G and M proteins was not serotype specific, but no interaction between the vesicular stomatitis virus M protein and the influenza virus hemagglutinin could be detected. These results support the conclusion that the interactions described here are the ones that govern assembly of G protein into virus envelopes in vivo. PMID- 1309252 TI - The varicella-zoster virus immediate-early protein IE62 is a major component of virus particles. AB - Varicella-zoster virus (VZV) open reading frame (ORF) 62 potentially encodes a protein with considerable amino acid homology to the herpes simplex virus (HSV) immediate-early regulatory polypeptide ICP4 (or IE3). To identify and characterize its protein product(s) (IE62), we used a rabbit antiserum prepared against a synthetic peptide corresponding to the C-terminal 13 amino acids of the predicted protein. This antiserum reacted with phosphorylated polypeptides of 175 to 180 kDa that were made in VZV-infected cells and in cells infected with a vaccinia virus recombinant expressing IE62, but not in control-infected cells, confirming its specificity and reactivity to the IE62 protein. The antiserum recognized a 175-kDa polypeptide in purified virions that comigrated with a major structural protein. Comparison of this reactivity with that of an antipeptide antiserum directed against the VZV ORF 10 product (homologous to the HSV major structural protein VP16) indicates similar levels of ORF 62 and ORF 10 polypeptides in VZV virions. In contrast, antipeptide antiserum directed against the VZV ORF 29 product, the homolog of the HSV major DNA-binding protein, failed to recognize any protein in our virion preparations. Treatment of virions with detergents that disrupt the virion envelope did not dissociate IE62 from the nucleocapsid-tegument structure of the virion. Differential sensitivity of VZV virion IE62 to trypsin digestion in the presence or absence of Triton X-100 indicates that IE62 is protected from trypsin degradation by the virus envelope; since it is not a nucleocapsid protein, we conclude that it is part of the tegument. Finally, we show that the virion 175-kDa protein either can autophosphorylate or is a major substrate in vitro for virion-associated protein kinase activity. PMID- 1309253 TI - Enhancement of transforming potential of human insulinlike growth factor 1 receptor by N-terminal truncation and fusion to avian sarcoma virus UR2 gag sequence. AB - The human insulinlike growth factor 1 (hIGF-1) receptor (hIGFR) is a transmembrane protein tyrosine kinase (PTK) molecule which shares high sequence homology in the PTK domain with the insulin receptor and, to a lesser degree, the ros transforming protein of avian sarcoma virus UR2. To assess the transforming potential of hIGFR, we introduced the intact and altered hIGFR into chicken embryo fibroblasts (CEF). The full-length hIGFR cDNA (fIGFR) was cloned into a UR2 retroviral vector, replacing the original oncogene v-ros. fIGFR was able to promote the growth of CEF in soft agar and cause morphological alteration in the absence of added hIGF-1 to medium containing 11% calf and 1% chicken serum. The transforming ability of hIGFR was not further increased in the presence of 10 nM exogenous hIGF-1. The 180-kDa protein precursor of hIGFR was synthesized and processed into alpha and beta subunits. The overexpressed hIGFR in CEF bound hIGF 1 with high affinity (Kd = 5.4 x 10(-9) M) and responded to ligand stimulation with increased tyrosine autophosphorylation. The cDNA sequence coding for part of the beta subunit of hIGFR, including 36 amino acids of the extracellular domain and the entire transmembrane and cytoplasmic domains, was fused to the 5' portion of the gag gene in the UR2 vector to form an avian retrovirus. The resulting virus, named UIGFR, was able to induce morphological transformation and promote colony formation of CEF with a stronger potency than did fIGFR. The UIGFR genome encodes a membrane-associated, glycosylated gag-IGFR fusion protein. The specific tyrosine phosphorylation of the mature form of the fusion protein, P75, is sixfold higher in vitro and threefold higher in vivo than that of the native IGFR beta subunit, P95. In conclusion, overexpression of the native or an altered hIGFR can induce transformation of CEF with the gag-IGFR fusion protein possessing enhanced transforming potential, which is consistent with its increased in vitro and in vivo tyrosine phosphorylation. PMID- 1309254 TI - The fibroblast growth factor receptor is not required for herpes simplex virus type 1 infection. AB - The early events mediating herpes simplex virus type 1 (HSV-1) infection include virion attachment to cell surface heparan sulfates and subsequent penetration. Recent evidence has suggested that the high-affinity fibroblast growth factor (FGF) receptor mediates HSV-1 entry. This report presents three lines of experimental evidence showing that the high-affinity FGF receptor is not required for HSV-1 infection. First, rat L6 myoblasts lacking FGF receptors were as susceptible to HSV-1 infection as L6 cells genetically engineered to express the FGF receptor. Second, a soluble FGF receptor fragment that inhibited FGF binding and receptor activation did not inhibit HSV-1 infection. Finally, basic FGF (but not acidic FGF) inhibited HSV-1 infection in L6 cells lacking FGF receptors, presumably by blocking cell surface heparan sulfates also required for HSV-1 infection. These results show that the high-affinity FGF receptor is not required for HSV-1 infection but instead that specific low-affinity basic FGF binding sites are used for HSV-1 infection. PMID- 1309256 TI - Characterization of an R-binding site mediating the R-induced activation of the Epstein-Barr virus BMLF1 promoter. AB - In cells latently infected with Epstein-Barr virus, the switch from latency to productive infection is linked to the expression of two Epstein-Barr virus transcription factors called EB1 and R. R is an enhancer factor, and an R responsive element (RRE) has been identified in the BMLF1 promoter. In this study, we have used bidirectional deletion mutagenesis to delineate the BMLF1 RRE (RRE-M) to a 44-bp sequence. We also show that R expressed from a recombinant vaccinia virus protects RRE-M against digestion by DNase I. Using mobility shift assays and dimethyl sulfate interferences, we have characterized the contact points between in vitro-translated R and the DNA. R binds in vitro to one site by simultaneously contacting two sequences within the site, which are separated by 8 bp: 5'-catGTCCCtctatcatGGCGCagac-3'. Site-directed mutagenesis of this sequence completely impaired the binding of R in vitro and rendered the BMLF1 promoter nonresponsive to R. The results suggest that the R-inducible BMLF1 enhancer is composed of a single R-binding site, called RRE-M. PMID- 1309255 TI - The UL5 gene of herpes simplex virus type 1: isolation of a lacZ insertion mutant and association of the UL5 gene product with other members of the helicase primase complex. AB - The UL5 gene product is required continuously during viral DNA synthesis (L. Zhu and S. K. Weller, Virology 166:366-378, 1988) and has been shown to be a component of a three protein helicase-primase complex encoded by herpes simplex virus type 1 (J. J. Crute, T. Tsurumi, L. Zhu, S. K. Weller, P.D. Olivo, M. D. Challberg, E. S. Mocarski, and I. R. Lehman, Proc. Natl. Acad. Sci. USA 86:2186 2189, 1989). The other members of the complex are viral proteins encoded by genes UL8 and UL52. In this study, we isolated a permissive cell line (L2-5) which contains the wild-type UL5 gene under the control of the strong and inducible promoter for the large subunit of herpes simplex virus type 1 ribonucleotide reductase (ICP6). An insertion mutant containing a mutation in the UL5 gene (hr99) was isolated by using the insertional mutagen ICP6::lacZ, in which the Escherichia coli lacZ gene is expressed under control of the viral ICP6 promoter. When grown on Vero cells, hr99 does not form plaques or synthesize viral DNA, although both defects are complemented efficiently on the L2-5 cells. These results confirm that the UL5 gene product is essential for viral growth and DNA replication. Furthermore, since no detectable UL5 protein is synthesized in hr99 infected cells, these cells provide a valuable control not only for the detection of the UL5 protein itself but also for the detection of protein-protein interactions with UL8 and UL52 by coimmunoprecipitation. In addition, the lacZ insertion in hr99 provides a convenient screening system for the introduction of site-specific mutations into the viral genome (L. Zhu and S. K. Weller, J. Virol. 66:469-479, 1992). Thus, hr99 is a valuable tool in the structure-function analysis of the UL5 gene. PMID- 1309257 TI - The six conserved helicase motifs of the UL5 gene product, a component of the herpes simplex virus type 1 helicase-primase, are essential for its function. AB - The UL5 protein of herpes simplex virus type 1, one component of the viral helicase-primase complex, contains six sequence motifs found in all members of a superfamily of DNA and RNA helicases. Although this superfamily contains more than 20 members ranging from bacteria to mammalian cells and their viruses, the importance of these motifs has not been addressed experimentally for any one of them. In this study, we have examined the functional significance of these six motifs for the UL5 protein through the introduction of site-specific mutations resulting in single amino acid substitutions of the most highly conserved residues within each motif. A transient replication complementation assay was used to test the effect of each mutation on the function of the UL5 protein in viral DNA replication. In this assay, a mutant UL5 protein expressed from an expression clone is used to complement a replication-deficient null mutant with a mutation in the UL5 gene for the amplification of herpes simplex virus origin containing plasmids. Eight mutations in conserved regions and three similar mutations in nonconserved regions of the UL5 gene were analyzed, and the results indicate that all six conserved motifs are essential to the function of UL5 protein in viral DNA replication; on the other hand, mutations in nonconserved regions are tolerated. These data provide the first direct evidence for the importance of these conserved regions in any member of the superfamily of DNA and RNA helicases. In addition, three motif mutations were introduced into the viral genome, and the phenotypic analyses of these mutants are consistent with results from the transient replication complementation assay. The ability of these three mutant UL5 proteins to form specific interactions with other members of the helicase-primase complex, UL8 and UL52, indicates that the functional domains required for replication activity of UL5 are separable from domains responsible for protein-protein interactions. It is anticipated that this type of structure function analysis will lead to the identification of protein domains that contribute not only to the enzymatic activities of helicase or primase but also to protein-protein interactions within members of the complex. PMID- 1309258 TI - EBNA1 can link the enhancer element to the initiator element of the Epstein-Barr virus plasmid origin of DNA replication. AB - The plasmid origin of DNA replication of Epstein-Barr virus, oriP, is replicated once per cell division, employing cellular replication machinery and only one viral protein. To understand how replication from this origin is initiated and regulated, we purified this viral protein, EBNA1. EBNA1 was expressed in CV-1p cells by using an infectious simian virus 40 vector containing the EBNA1 gene. It was purified in two chromatographic steps to apparent homogeneity. The purified protein is capable of supporting transcription of the luciferase gene from a reporter plasmid carrying the FR enhancer element to which EBNA1 binds. EBNA1 does not have oriP-dependent ATPase activity, indicating that it does not carry out an energy-dependent step in the initiation of DNA replication. However, EBNA1 does mediate an association between the two elements of oriP. We measured this association by binding one of the elements, the enhancer element, to a solid matrix and measuring retention by this element of the other one, the initiator element, in the presence of EBNA1. This retention is specific for DNA fragments containing EBNA1-binding sites. EBNA1 thus can link the two elements of the origin, providing a locally high concentration of EBNA1 at the site of initiation of DNA replication. We propose that this association is important either (i) to affect DNA structure to allow a cellular helicase to initiate DNA strand separation or (ii) to bind replication proteins to bring them to the origin of replication. PMID- 1309259 TI - Host cell and EBNA-2 regulation of Epstein-Barr virus latent-cycle promoter activity in B lymphocytes. AB - The six latent-cycle nuclear antigens (EBNAs) of Epstein-Barr virus (EBV), whose genes share 5' leader exons and two promoters (Cp and Wp), are differentially expressed by cells of the B lineage. To examine the possibility that EBNA gene expression is regulated through selective use of Cp and Wp, we monitored the activity of promoter-chloramphenicol acetyltransferase (CAT) gene constructs transfected into EBV-positive and EBV-negative B lymphocytes and Burkitt's lymphoma cells. Wp was a much stronger promoter than Cp in EBV genome-negative B cell lines and was used exclusively in primary B cells. When B cells were infected with transforming EBV, Cp became the stronger promoter. This switch was not observed when B cells were infected with an immortalization-deficient virus, P3HR-1, which lacks the EBNA-2 open reading frame and expresses a mutant leader protein (EBNA-LP). Cp function was transactivated when EBV-negative or P3HR-1 infected B cells were cotransfected with Cp and a 12-kb fragment of DNA (BamHI WWYH) that spanned the P3HR-1 deletion. This activity was mapped to the EBNA-2 gene within WWYH; constructs expressing EBNA-LP did not induce Cp function, and the deletion of 405 bp from the EBNA-2 open reading frame abolished transactivation. This research demonstrates host cell and EBNA-2 regulation of latent-cycle promoter activity in B lymphocytes, a mechanism with implications for persistence of EBV-infected lymphoid cells in vivo. PMID- 1309260 TI - Activation of the c-myb locus is insufficient for the rapid induction of disseminated avian B-cell lymphoma. AB - We have previously reported that infection of 9- to 13-day-old chicken embryos with RAV-1 results in rapid development of a novel B-cell lymphoma in which proviral insertion has activated expression of the c-myb gene (E. Pizer and E. H. Humphries, J. Virol. 63:1630-1640, 1989). The biological properties of these B cell lymphomas are distinct from those associated with the B-cell lymphomas that develop following avian leukosis virus proviral insertion within the c-myc locus. In an extension of this study, more than 200 chickens, infected as 10- to 11-day old embryos, were examined for development of lymphomas that possess disrupted c myb loci. Fourteen percent developed disseminated B-cell lymphoma. In the majority of these tumors, the RAV-1 provirus had inserted between the first and second exons that code for p75c-myb. However, insertions between the second and third exons and between the third and fourth exons were also detected. In situ analysis of myb protein expression in tumor tissue revealed morphological features suggesting that the tumor originates in the bursa. Within the bursa, the lymphoma appeared to spread from follicle to follicle without compromising the structural integrity of the organ. Tumor masses in liver demonstrated heterogeneous levels of myb protein suggestive of biologically distinct subpopulations. In contrast to the morbidity data, immunohistological analysis of bursae from 4- to 6-week-old chickens at risk of developing lymphomas bearing altered c-myb loci revealed lesions expressing elevated levels of myb in 16 of 19 birds. The activated myb lymphoma displayed very poor capacity to proliferate outside its original host. Only 1 of 33 in vivo transfers of tumor to recipient hosts established a transplantable tumor. None of the primary tumor tissue nor the transplantable tumor exhibited the capacity for in vitro proliferation. Similar experimental manipulation has yielded in vitro lines established from avian B-cell lymphomas expressing elevated levels of c-myc or v-rel. The dependence on embryonic infection for development of activated-myb lymphoma suggests a requirement for a specific target cell in which c-myb is activated by proviral insertion. It is likely, moreover, that continued tumor development requires elevated expression of myb proteins within a specific cell population in a restricted stage of differentiation. PMID- 1309261 TI - Polyomavirus large and small T antigens cooperate in induction of the S phase in serum-starved 3T3 mouse fibroblasts. AB - The induction of an S phase in the host cell is a prerequisite for the lytic replication cycle of polyomavirus. This function was attributed to proteins coded for by the early region of the viral DNA, the T antigens. A consideration of the role of the T antigens in the initiation of a mitogenic response of the host cell has to take into account the recent discovery that virus adsorption is sufficient to induce the synthesis of proteins which are known to appear early after quiescent cells are stimulated by the addition of serum, namely fos, jun, and myc (J. Zullo, C.D. Stiles, and R.L. Garcea, Proc. Natl. Acad. Sci. USA 84:1210-1214, 1987; G. M. Glenn and W. Eckhart, J. Virol. 64:2193-2201, 1990). This induction is followed by an initiation of DNA synthesis. It is therefore important to dissociate the effects of the T antigens on the host cell from those of virus adsorption. To do so, we used dexamethasone-regulated versions of the large and small T antigens of polyomavirus stably integrated into the genome of Swiss 3T3 cells to study their function in S-phase induction. When the production of the large or small T antigen in serum-starved 3T3 mouse fibroblasts was activated, only a small fraction of cells was able to leave G0/G1 despite the synthesis of considerable amounts of the respective T antigen. Activation of both T antigens within the same cell, on the other hand, resulted in S-phase induction in a notable percentage of cells, suggesting that the two proteins cooperate in this activity. Polyomavirus T antigens appear to bypass the pathway of growth regulation involving the activation of c-fos. These results are discussed in relation to other known functions of the two virally coded proteins. PMID- 1309262 TI - Herpes simplex virus envelopment and maturation studied by fracture label. AB - Herpes simplex virus envelopment and maturation were investigated by thin-section fracture label. The distribution of glycoproteins B and D was analyzed by labeling with antibodies; the precursor and mature forms of the glycoproteins were differentiated by labeling with the lectins concanavalin A (ConA) and wheat germ agglutinin (WGA), respectively. We report that the two glycoproteins were readily detected in the intracellular virion, whether located between the inner and outer nuclear membranes or within cytoplasmic membrane-bound vesicles and in the inner and outer nuclear membranes themselves. The enveloped virion between the inner and outer nuclear membranes labeled with ConA but not with WGA. During the transit to the extracellular space the reactivity of the virion membranes with ConA decreased and that with WGA ensued. The results document that herpes simplex viruses acquire at the inner nuclear membrane an envelope carrying the immature forms of the glycoproteins and that during the transit to the extracellular space the envelope glycoproteins become of the fully processed type. PMID- 1309263 TI - The unique sequence of the herpes simplex virus 1 L component contains an additional translated open reading frame designated UL49.5. AB - We present evidence for the existence of an additional herpes simplex virus 1 gene designated UL49.5. The sequence, located between genes UL49 and UL50, predicts a hydrophobic protein with 91 amino acids. Attempts to delete UL49.5 were not successful. To demonstrate that UL49.5 is expressed, we made two recombinant viruses. First, we inserted in frame an oligonucleotide encoding a 15 amino-acid epitope known to react with a monoclonal antibody. This gene, consisting of the authentic promoter and chimeric coding domain, was inserted into the thymidine kinase gene of wild-type virus and in infected cells expressed a protein which reacted with the monoclonal antibody. The second recombinant virus contained a 5' UL49.5-thymidine kinase fusion gene. The protein expressed by this virus confirmed that the first methionine codon of UL49.5 served as the initiating codon. The predicted amino acid sequence of UL49.5 is consistent with the known properties of NC-7, a small capsid protein whose gene has not been previously mapped. A homolog of UL49.5 is present in the genome of varicella zoster virus, located between homologs of UL49 and UL50. PMID- 1309264 TI - Intronic sequences and 3' splice sites control Rous sarcoma virus RNA splicing. AB - cis-acting sequences of Rous sarcoma virus (RSV) RNA involved in control of the incomplete splicing that is part of the retroviral life cycle have been studied. The 5' and two alternative 3' splice sites, as well as negative regulator of splicing element in the intron, have been introduced into chimeric constructs, and their responsive roles in splicing inhibition have been evaluated by transient transfection experiments. Although the RSV 5' splice site was used efficiently in these assays, substrates containing either the RSV env or the RSV src 3' splice site were not spliced completely, resulting in 40 to 50% unspliced RNA. Addition of the negative regulator of splicing element to substrates containing RSV 3' splice sites resulted in greater inhibition of splicing (70 to 80% unspliced RNA), suggesting that the two elements function independently and additively. Deletion of sequences more than 70 nucleotides upstream of the src 3' splice site resulted in efficient splicing at this site, suggesting that inefficient usage is not inherent in this splice site but is instead due to to sequences upstream of it. Insertion of these upstream sequences into the intron of a heterologous pre-mRNA resulted in partial inhibition of its splicing. In addition, secondary structure interactions were predicted to occur between the src 3' splice site and the inhibitory sequences upstream of it. Thus, RSV splicing control involves both intronic sequences and 3' splice sites, with different mechanisms involved in the underutilization of the env and src splice acceptor sites. PMID- 1309265 TI - Reciprocal antagonism of steroid hormones and BZLF1 in switch between Epstein Barr virus latent and productive cycle gene expression. AB - BZLF1 repression of transcription from the Epstein-Barr virus BC-R2 promoter (Cp) was shown to require a glucocorticoid response element in cis and glucocorticoids in trans. The mechanism of the repression is indirect and involves up regulation of the cellular c-fos proto-oncogene. Glucocorticoids maintain Epstein-Barr virus latency, and removal of glucocorticoids from the cell culture medium results in activation of the productive cycle. This inverse regulation of the expression of latent and productive cycle genes contributes to the switch between virus latency and the productive cycle. Glucocorticoid control of BC-R2 might also provide a mechanism for EBNA promoter switching during early infection and in development of the restricted latent pattern of gene expression. PMID- 1309267 TI - From the National Institutes of Health. PMID- 1309266 TI - Identification of a unique Marek's disease virus gene which encodes a 38 kilodalton phosphoprotein and is expressed in both lytically infected cells and latently infected lymphoblastoid tumor cells. AB - The identification of unique Marek's disease (MD) virus (MDV) antigens expressed not only in lytically infected cells but also in latently infected MD lymphoblastoid tumor cell lines is important in understanding the molecular mechanisms of latency and transformation by MDV, an oncogenic lymphotropic herpesvirus of chickens. Through cDNA and nucleotide sequence analysis, an open reading frame (designated the pp38 ORF) which encodes a predicted polypeptide of 290 amino acids was identified in BamHI-H. Demonstration that the pp38 ORF spans the junction of the MDV long unique and long internal repeat regions (MDV has an alphaherpesvirus genome structure) precludes the presence of the gene encoding the B-antigen complex (gp100, gp60, and gp49) in the same region of BamHI-H, where it was originally thought to exist. Duplication of the complete pp38 ORF was not observed in BamHI-D, but part of it (encoding 45 amino acids) was found in the long terminal repeat region of the fragment. By use of trpE-pp38 fusion proteins, antisera against pp38 were prepared. By immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a predominant virus-specific 38,000-dalton polypeptide (designated pp38) and a minor 24,000-dalton polypeptide (designated p24) were found. No precursor-product relationship was found between pp38 and p24 by pulse-chase analysis, and only pp38 was detected by Western blot (immunoblot) analysis with antiserum to pp38. pp38 was found to be phosphorylated and present in oncogenic serotype 1-but not nononcogenic serotype 3-infected cells. Expression of the gene encoding pp38 was relatively insensitive to phosphonoacetic acid inhibition, suggesting that pp38 may belong to one of the early classes of herpesvirus proteins. pp38 was also detected in the latently infected MSB-1 lymphoblastoid tumor cell line. The detection of antibody against pp38 in immune chicken sera indicates that pp38 is an immunogen in birds with MD. Most of the properties described here for a protein detected by methods based on finding the ORF first are identical to those of a 38-kDa phosphoprotein reported by others, suggesting that they are the same. Collectively, the data reported here provide (i) more definitive information on the complete ORF of another MDV gene and the protein that it encodes, (ii) clarification of the gene content within a specific region of the MDV genome, and (iii) the molecular means to conduct further studies to determine whether pp38 plays a role in MDV latency and transformation. PMID- 1309268 TI - Medical management of AIDS patients. Ophthalmic problems. AB - The majority of AIDS patients will develop ocular complications at some point during the course of their illness. The most common complications involve the retina. Accurate diagnosis of noninfectious and infectious (especially CMV) retinopathy is extremely important as most forms of infectious retinitis can be treated, albeit not without significant complications in many cases. Close cooperation between the ophthalmologist and internist is essentially to ensure that timely therapeutic intervention, which can dramatically reduce the risk of visual impairment and blindness, can be initiated. AIDS-related diseases of the central nervous system, especially nonviral infections, are often associated with abnormalities of ocular function. Assessment of visual acuity, visual fields, extraocular movements, pupillary reflexes, color perception, and the condition of optic nerve and retina is important for accurate diagnosis. PMID- 1309269 TI - Relation of meat, fat, and fiber intake to the risk of colon cancer in women. PMID- 1309270 TI - Diagnosis of cytomegalovirus pancreatitis in AIDS by endoscopic retrograde cholangiopancreatography. PMID- 1309272 TI - Replication and persistence of HPV DNA in cultured cells derived from laryngeal papillomas. AB - We have investigated the replication and persistence of human papillomavirus (HPV) type 6 and 11 DNA in cultured cells derived from laryngeal papillomas, with paradoxical findings. Measured by bromodeoxyuridine incorporation into heavy/light DNA separated on a cesium chloride gradient, viral DNA replicates in both primary and secondary cells. The ratio of the fraction of replicated viral to replicated cellular DNA was equal to or greater than 1 in all but one case and was closer to 2 in primary cells. Despite this efficient replication, HPV DNA is rapidly lost from the cells with passage. We propose that infected cells, or those with a high HPV copy number, show a selective decrease in plating efficiency compared to uninfected cells or those with a low copy number, which explains the loss of HPV DNA with repeated passage. PMID- 1309271 TI - MHV S peplomer protein expressed by a recombinant vaccinia virus vector exhibits IgG Fc-receptor activity. AB - We have previously shown that cells infected with mouse hepatitis virus (MHV) bind rabbit, mouse, and rat IgG by the Fc portion of the IgG molecule. This Fc binding activity appeared to be mediated by the MHV S protein. S protein could also be precipitated from MHV-infected cells by a monoclonal antibody directed against the murine Fc gamma receptor (Fc gamma R). To prove definitively that the S protein mediates Fc-binding activity, we have expressed the MHV S protein utilizing recombinant vaccinia viruses. The anti-Fc gamma R monoclonal antibody, 2.4G2, precipitated recombinant S protein in cells of murine, human, and rabbit origin. Since the anti-Fc receptor monoclonal antibody does not react with human and rabbit Fc receptors these results demonstrate that the epitope recognized by this antibody is carried on the MHV S protein and is not murine in origin. Examination of various MHV isolates and escape mutants failed to identify the precise sequences in S responsible for the molecular mimicry of the murine Fc gamma R. These data are consistent with the hypothesis that a previously identified region of similarity between the S protein and the Fc gamma R mediates this activity. The Fc binding activity of S was expressed on the cell surface, since MHV-JHM-infected cells, but not uninfected cells, formed rosettes with anti sheep red blood cell (SRBC) antibody-coated SRBC. The anti-Fc gamma R monoclonal antibody neutralized MHV-JHM and inhibited syncytium formation induced by the MHV S protein. PMID- 1309274 TI - Deletion of the growth factor gene related to EGF and TGF alpha reduces virulence of malignant rabbit fibroma virus. AB - The role of the epidermal growth factor homologue in malignant rabbit fibroma virus (MRV) pathogenicity was investigated by constructing a viral growth factor deletion mutant (MRV-GF-). Since MRV is a recombinant virus with a myxoma virus background but possesses some terminal sequences derived from Shope fibroma virus, the growth factor gene in MRV is in fact identical to Shope fibroma growth factor (SFGF). Although no significant differences were detected in the in vitro characteristics of MRV and MRV-GF-, a pronounced attenuation was observed after inoculation of the test rabbits with MRV-GF-. Animals infected with wild-type MRV uniformly developed a fatal syndrome involving disseminated tumors accompanied by purulent conjunctivitis and rhinitis. In contrast, although MRV-GF- recipients developed similar initial signs of the MRV disease syndrome, 75% of these animals completely recovered from the viral and secondary bacterial infections and became immune to subsequent MRV challenge. Tumors in MRV-GF- recipients displayed earlier and more prominent inflammatory reactions than their wild-type MRV counterparts and contained fewer proliferating cells. Squamous metaplasia and hyperplasia of target epithelia were less pronounced in MRV-GF- than in MRV infection. We conclude that SFGF is a major virulence factor in MRV infection and is responsible for at least some of the cellular proliferation observed at tumor sites. In addition, the diminished ability of MRV-GF- to cause hyperplasia in nasal and conjunctival epithelia may decrease the extent of gram negative bacterial overgrowth as compared to the parental virus and hence contribute to the dramatic reduction in the lethality of MRV-GF- infection. PMID- 1309273 TI - Sequences present in a small region of the AKV virus envelope gene determine the efficiency with which pseudotyped spleen focus-forming virus infects erythroid target cells. AB - Induction of erythroleukemia in mice by the replication-defective spleen focus forming virus (SFFV) relies on the presence of a helper virus to deliver the SFFV genome to erythroid target cells. Pseudotyping studies with different ecotropic murine leukemia viruses (MuLV) have shown that SFFV pseudotyped with Akv, the endogenous ecotropic virus of AKR mice, inefficiently gives rise to virus-induced erythroid bursts (vBFU-E) in vitro and fails to cause erythroleukemia in mice when compared to SFFV pseudotyped with Friend or Moloney MuLV. In order to locate the region(s) of the Akv genome responsible for its inability to act as a helper for SFFV, six different Moloney MuLV chimeras containing Akv envelope sequence substitutions were constructed. Virions with the chimeric envelopes were used to pseudotype SFFV and the complexes were analyzed for their ability to induce vBFU E in vitro and erythroleukemia in mice. SFFV preparations pseudotyped with three of the constructs containing chimeric envelope genes efficiently gave rise to vBFU-E as did SFFV pseudotyped with Moloney MuLV. SFFV pseudotypes generated from the other three constructs, which all share a common 304-bp region located near the center of the Akv gp70 coding region, and Akv gave rise to very few vBFU-E. However, all SFFV preparations, with the exception of SFFV pseudotyped with Akv, induced erythroleukemia in mice. The results suggest that specific sequences present in the envelope gene of Akv are responsible for the inefficiency of the virus to infect erythroid target cells for SFFV, but additional Akv sequences outside those used in this study affect the ability of the Akv/SFFV virus complex to cause erythroleukemia in mice. PMID- 1309275 TI - Determinants of rotavirus stability and density during CsCl purification. AB - The stability of rotavirus infectivity during CsCl gradient purification and subsequent storage was examined using our standard SA11 wild type (SA11-Cl3), the SA11 4F variant (SA11-4F), bovine rotavirus B223, and a panel of bi- and triparental reassortants derived from these parental viruses. Viral stability was determined by the recovery of infectivity at each step during a standard CsCl purification protocol. SA11-4F was the most stable parent (91-93% recovery), SA11 Cl3 had intermediate stability (10-21% recovery), and B223 was least stable (0.5 7% recovery). Among the reassortants, the recovery varied from 0.5 to 88.6% of the initial infectivity and was determined primarily by the parental origin of genome segment 4. The greatest loss of infectivity occurred during Freon extraction, with smaller losses during the CsCl gradient, and the smallest loss during the virus pelleting step. Comparison of the stability of viruses grown in the presence or absence of exogenous trypsin revealed that, in general, viruses grown in the absence of trypsin were more stable during purification. During 4-5 months storage at 4 degrees, the differences in stability of parental and reassortant viruses were not as dramatic as during purification and were not significantly affected by the presence or absence of trypsin during growth. However, survival during storage was as low as 4% and as high as 100% and was also primarily dependent on the parental origin of genome segment 4. It was noted that bovine rotavirus B223 had higher density in CsCl than either SA11-Cl3 or SA11-4F. The observation of heterogeneity in density was investigated using reassortants. These results indicated that all reassortants had intermediate density and suggested that physical interactions among the structural proteins were responsible for the heterogeneity in density. The possible roles of viral structural proteins in rotavirus stability and the relationship between the stability and the density are discussed. PMID- 1309276 TI - A system for the high efficiency replication of HIV-1 in neural cells and its application to anti-viral evaluation. AB - Stable transfection of H4 neuroglioma cells with the Epstein-Barr virus-based eucaryotic CD4 expression vector pKS286 generated the cell line, H4/CD4, in which greater than 90% of cells express surface CD4 receptors. Optimal conditions for infection of H4/CD4 cells with HIV-1 were determined; these included a cocultivation with growth-arrested, chronically infected T cells. Under these conditions, 3-days after infection up to 50% of H4/CD4 cells expressed HIV-1 antigens as detected by immunofluorescence assay, the number of intracellular HIV 1 RNA copies reached 10(3) molecules per cell as determined by liquid hybridization, and virus production ranged from 0.2 to 1.0 micrograms HIV-1 p24 core antigen per ml of culture supernatant, comparable to that measured under the same conditions in HIV-1 infected T cells. Giant cells and cytolysis were common. Inhibition of HIV-1 infection by nucleoside analogues in H4/CD4 cells was comparable to that in T cells, suggesting that the early stages of HIV-1 infection were similar in both cell systems. Infection in the presence of soluble CD4 reduced HIV-1 expression to the levels determined in CD4-negative H4 cells. This system may be useful for screening of drugs intended to block HIV-1 replication in the brain and for the evaluation of the HIV-1 life cycle in brain cells. PMID- 1309277 TI - A possible role for nonsense suppression in the synthesis of a human cytomegalovirus 58-kDa virion protein. AB - A 1.6-kb late mRNA originating from the HindIII R fragment of human cytomegalovirus (HCMV) encodes a 58-kDa virion phosphoprotein. Data presented support the hypothesis that this protein may be synthesized via the translational readthrough of an opal termination codon separating two open reading frames located in tandem. To our knowledge this is the first report of nonsense suppression as a means of regulating gene expression in HCMV. PMID- 1309278 TI - Human papillomavirus type 42: new sequences, conserved genome organization. AB - We report the nucleotide sequence and genome organization of the human papillomavirus type 42. HPV42 DNA was isolated from vulvar papillomas. It has been detected in benign forms of proliferative lesions only. The genome of HPV42 is 7917 bp long and shows the open reading frame pattern conserved in all HPVs sequenced so far. HPV42 has no high degree of sequence homology to any of the known HPVs. It shows characteristics previously found either exclusively in HPVs associated with invasive carcinomas or exclusively in nongenital HPVs. Therefore it cannot be readily ascribed to any of the established subgroups of human papillomaviruses. PMID- 1309279 TI - Differences in the integration pattern and episomal forms of human papillomavirus type 16 DNA found within an invasive cervical neoplasm and its metastasis. AB - Human papillomavirus (HPV) type 16 DNA was found in three separate neoplastic lesions within a female patient. The physical state of the viral DNA in each lesion was determined by two-dimensional agarose gel electrophoresis. The primary cervical tumor contained large amounts of several distinct episomal forms as well as integrated HPV DNA. Metastatic tumor tissue found in the vagina had greatly reduced levels of episomal DNA and a viral DNA integration pattern that was different from that of the primary tumor. The vulvar carcinoma in situ had what appears to be free and integrated forms of viral DNA. The results show that although metastatic tissue retained HPV DNA, further rearrangements of the integrated viral DNA pattern found in the primary tumor may occur with a dramatic decrease of episomal forms during malignant progression. PMID- 1309280 TI - Identification of two new polypeptides encoded by mRNA5 of the coronavirus infectious bronchitis virus. AB - The second smallest subgenomic messenger RNA, mRNA5, of the coronavirus infectious bronchitis virus includes in its "5' unique region" two separate open reading frames (5a and 5b), whose coding function has not so far been established, and thus it may represent a dicistronic messenger RNA. We report here that two polypeptides with the sizes expected for the 5a and 5b products can be synthesised by in vitro translation of a single artificial mRNA containing both the 5a and 5b ORFs. To establish whether these polypeptides represent genuine virus gene products, both the 5a and 5b coding sequences were expressed as bacterial fusion proteins, and these were used to raise monospecific antisera. Antisera raised against both the 5a and 5b-specific sequences recognized specifically proteins of the expected size in infectious bronchitis virus infected chicken kidney and Vero cells, indicating that 5a and 5b do represent genuine virus genes, and suggesting that mRNA5 is indeed functionally dicistronic. PMID- 1309281 TI - The first 124 nucleotides of the E7 coding sequences of HPV16 can render the HPV11 genome transformation competent. AB - The human papillomavirus (HPV) type 16 is associated with the majority of cervical tumors and is capable of oncogenically transforming cells in culture. HPV type 11 is rarely associated with malignant lesions and does not transform cells in vitro. While the E7 of HPV16 is necessary and sufficient for transformation of rodent cells, the E7 gene of HPV11 is not transforming. In the present report we demonstrate that the HPV11 genome, with the first 124 nucleotides of the HPV16 E7 open reading frame fused to the last 198 nucleotides of the HPV11 E7 open reading frame, becomes transformation competent. PMID- 1309282 TI - Genes homologous to ubiquitin-conjugating proteins and eukaryotic transcription factor SII in African swine fever virus. AB - The nucleotide sequence of the 6004-bp EcoRI I fragment of African swine fever virus DNA has been determined. Translation of the sequence revealed eight closely spaced open reading frames (ORFs), three of them reading rightward and five leftward. Northern blot hybridization analysis indicated that ORFs I73R and I78R were transcribed early in infection, whereas ORFs I177L, I196L, and I329L were expressed at late times. Transcripts for ORFs I215L, I226R, and I243L were detected at low levels in early RNA and at higher levels in late RNA. The intergenic regions between genes I73R/I329L and I78R/I215L were characterized by the presence of direct repeats in tandem. Direct repetitions were also found within ORF I196L. The protein encoded by ORF I329L contained a putative cleavable signal peptide and an internal transmembrane domain, and that encoded by ORF I177L had an amino-terminal hydrophobic region with the characteristics of a "start-stop" sequence. ORF I243L encoded a protein similar to the eukaryotic elongation factor SII. The protein encoded by ORF I215L was homologous to the family of ubiquitin-conjugating proteins. PMID- 1309283 TI - Evidence that the herpes simplex virus immediate early protein ICP27 acts post transcriptionally during infection to regulate gene expression. AB - The herpes simplex virus (HSV-1) immediate early protein ICP27 is a regulatory protein which is essential for virus replication. The phenotype of temperature sensitive and deletion mutants in ICP27 includes overexpression of some immediate early and early gene products and greatly reduced levels of late gene products. To determine whether regulation by ICP27 occurs primarily at the transcriptional level, we have studied the expression of two immediate early products (ICP4 and ICP27) and two late gene products (glycoprotein B and glycoprotein C) at the level of transcription initiation, accumulation of steady state mRNA, and protein synthesis in an ICP27 temperature-sensitive mutant tsLG4, compared to wild-type HSV-1. At the nonpermissive temperature in tsLG4-infected cells, the two immediate early gene products ICP4 and ICP27 were overexpressed both at the mRNA and protein level although synthesis of these transcripts as measured by nuclear runoff assays was reduced relative to the wild-type HSV-1 infections. The transcription of late gene products glycoprotein B (gB) and glycoprotein C (gC) was lower in runoff assays from tsLG4 infections suggesting that the reduction in the level of late products occurred at the transcriptional level. However, temperature shift experiments in which tsLG4-infected cells were shifted to the nonpermissive temperature at various times after infection showed that the synthesis of late transcripts was not altered 2 hr after the shift whereas both the accumulation of leaky late and late mRNA and the incorporation of [35S]methionine into newly synthesized gB and gC was reduced by 2 hr after the shift to nonpermissive temperature. Therefore, while the synthesis of new transcripts continued, the accumulation of late mRNAs and their translation into protein was reduced when ICP27 was defective, whereas, the converse was found for immediate early products. That is, the synthesis of new transcripts was reduced yet mRNA and protein accumulated to high levels. These results suggest that ICP27 acts at least in part post-transcriptionally to regulate the expression of immediate early and late gene products. PMID- 1309284 TI - Processing of the herpes simplex virus assembly protein ICP35 near its carboxy terminal end requires the product of the whole of the UL26 reading frame. AB - The herpes simplex virus (HSV) type 1 assembly protein ICP35 consists of a family of polypeptides, ranging in molecular weight from about 45,000-39,000. The lower molecular weight forms of ICP35 are derived from the higher molecular weight species by slow post-translational modification. The reading frame of gene UL26 and the region within this gene which exhibited homology to the cytomegalovirus assembly protein, the analogous protein to ICP35, were expressed separately under immediate-early (IE) gene regulation in a HSV vector containing a temperature sensitive mutation in the major transcriptional regulator Vmw175. Monoclonal antibody specific for ICP35 immunoprecipitated several polypeptides with molecular weights around 75,000 from extracts of cells infected with a recombinant expressing the IE gene UL26 at the nonpermissive temperature (NPT). These results suggested that the UL26 gene specified a protein distinct from ICP35 but which had some antigenic sites in common with ICP35. In extracts of cells infected at the NPT with a recombinant expressing only the carboxy terminal half of UL26 coding sequences, the monoclonal antibody immunoprecipitated large amounts of the high molecular weight forms of ICP35. The lower molecular weight processed forms of ICP35, however, were not detectable. When cells were coinfected with both recombinants ICP35 was processed to its lower molecular weight forms. This processing step, which occurred near the carboxy terminus of ICP35, was not dependent on capsid formation. The work, together with previous information on the processing of the CMV assembly protein, suggests that UL26 product may be a protease. PMID- 1309285 TI - A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. AB - OBJECTIVE: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset. DESIGN: Cohort study with comparison to matched, healthy control subjects. PATIENTS: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in. MAIN OUTCOME MEASURES: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6). MAIN RESULTS: Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P less than 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P less than 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-8], a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA. CONCLUSIONS: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen. PMID- 1309286 TI - Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study. AB - OBJECTIVE: To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma. DESIGN: Two pair-matched case-control studies. SETTING: A referral-based hospital. PATIENTS: In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma. MEASUREMENTS: Levels of antibody to HCV (anti-HCV), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B core antigen (anti-HBc) were assayed, and alcohol abuse was assessed by history. MAIN RESULTS: In study I, 151 patients (71%) with hepatocellular carcinoma were anti-HCV positive compared with 11 controls (5%) with chronic nonhepatic diseases (odds ratio, 42; 95% CI, 22 to 95). Multivariate analysis showed that anti-HCV was an independent risk factor for hepatocellular carcinoma (odds ratio, 69; CI, 15 to 308). The analysis also showed that HBsAg (odds ratio, 8.7; CI, 1.5 to 50) and anti-HBc (odds ratio, 4.2 (CI, 1.7 to 11) were risk factors for hepatocellular carcinoma. No statistically significant interaction was found between anti-HCV and the markers of HBV infection. In study II, 146 patients (74%) with hepatocellular carcinoma and cirrhosis were anti-HCV positive compared with 122 patients (62%) with cirrhosis alone (odds ratio, 1.8; CI, 1.1 to 2.8). Multivariate analysis confirmed that anti-HCV (odds ratio, 2.0; CI, 1.3 to 32) and HBsAg (odds ratio, 2.0; CI, 1.0 to 4.2) were independent risk factors for hepatocellular carcinoma. CONCLUSIONS: Hepatitis C virus infection is a risk factor for hepatocellular carcinoma, apparently by inducing cirrhosis and, to a lesser extent, by enhancing the risk in patients with cirrhosis. Hepatitis C virus infection acts independently of HBV infection (another risk factor) and of alcohol abuse, age, or gender. PMID- 1309287 TI - Properties of immunoaffinity purified 106-kDa Ca2+ release channels from the skeletal sarcoplasmic reticulum. AB - The sulfhydryl-gated 106-kDa Ca(2+)-release channel (SG-106) was purified by biotin-avidin chromatography from skeletal sarcoplasmic reticulum (SR) vesicles and used as an antigen to raise polyclonal antibodies. Western blots showed that the antisera crossreacted with the antigenic SG-106 and not with SR Ca2+, Mg(2+) ATPase or with junctional foot proteins (JFPs) (Zaidi et al., 1989, J. Biol. Chem. 264(36), 21, 725-21, 736; 21, 737-21, 747). Polyclonal antibody-affinity columns were used to selectively purify SG-106-kDa proteins which, upon incorporation in planar bilayers, revealed the presence of a cationic channels with properties similar to "native" Ca(2+)-release channels obtained through the fusion of SR vesicles with planar bilayers. In agreement with measurements of Ca2+ release from SR vesicles, sulfhydryl oxidizing and reducing agents (i.e., 2,2'-dithiodipyridine and dithiothreitol) respectively increased and decreased the open-time probability of 106-kDa Ca(2+)-release channels. In contrast with reports on JFPs, ryanodine at 0.5-1 nM increased the open-time probability and at 2-10 nM locked 106-kDa Ca(2+)-release channels in a closed state rather than an open subconductance state. The SG-106 was activated by millimolar ATP, inhibited by millimolar Mg2+, and blocked by micromolar ruthenium red. Adriamycin (2-10 microM) caused a transient activation of SG-106 Ca(2+)-release channels, followed by closure in about 5 min, and intermittent activation to a subconductance state. Polyclonal antibodies used to purify the SG-106 also activated the channel when added to the cis side but not the trans side of the bilayer. Thus, SG-106 channels possess features that are similar to "native" SR Ca(2+)-release channels, are immunologically distinct from JFPs, and interact in seconds with nanomolar ryanodine in planar bilayers. PMID- 1309288 TI - Sodium-coupled ATP synthesis in the bacterium Vitreoscilla. AB - The bacterium Vitreoscilla generates an electrical potential gradient due to sodium ion (delta psi Na+) across its membrane via respiratory-driven primary Na+ pump(s). The role of the delta psi Na+ as a driving force for ATP synthesis was, therefore, investigated. In respiring starved cells pulsed with 100 mM external Na+ [( Na+]o) there was a 167% net increase in cellular ATP concentration over basal levels compared with 0, 56, 78, and 78% for no addition, choline, Li+, and K+ controls, respectively. Doubling the [Na+]o to 200 mM boosted the net increase to 244% but a similar doubling of the choline caused only an increase to 78%. When the initial condition was intracellular Na+ ([Na+]i) = [Na+]o = 100 mM, there was a 94% net increase in cellular ATP compared with only 18 and 11% for Li+ and K+ controls, respectively, indicating that Nai+ may be the only cation tested that the cells extruded to generate the electrochemical gradient required to drive ATP synthesis. The Na(+)-dependent ATP synthesis was inhibited completely by monensin (12 microM), but only transiently by the protonophore 3,5 di-tert-butyl-4-hydroxybenzaldehyde (100 microM), further evidence that the Na+ gradient and not a H+ gradient was driving the ATP synthesis. ATP synthesis in response to an artificially imposed H+ gradient (delta pH approximately 3) in the absence of an added cation, or in the presence of Li+, K+, or choline, yielded similar delta ATP/delta pH ratios of 0.98-1.22. In the presence of Na+, however, this ratio dropped to 0.23, indicating that Na+ inhibited H(+)-coupling to ATP synthesis and possibly that H+ and Na+ coupling to ATP synthesis share a common catalyst. The above evidence adds to previous findings that under normal growth conditions Na+ is probably the main coupling cation for ATP synthesis in Vitreoscilla. PMID- 1309289 TI - A possible role of carbohydrate moieties in prostaglandin D2 and prostaglandin E2 receptor proteins from the porcine temporal cortex. AB - The binding activities of prostaglandins (PGs) D2 and E2 were measured after deglycosylation of P2 membranes prepared from the porcine temporal cortex in order to investigate the role of carbohydrate moieties in the receptor binding. PGD2 and PGE2 binding activities were significantly decreased by pretreatment with various exoglycosidases, such as neuraminidase for PGE2 binding, alpha mannosidase and beta-galactosidase for PGD2 binding, and beta-N acetylhexosaminidase for both. Further, peptide N-glycohydrolase F and endo-alpha N-acetylgalactosaminidase, which are specific for the cleavage of N-glycan and O glycan linkages, respectively, in glycoproteins were used. Pretreatment with either of them also reduced both PGD2 and PGE2 binding activities. The reduction was dependent on the pretreatment time and enzyme concentration. The time courses of the reduction were typically characterized by a marked increase in the nonspecific bindings. Scatchard plot analysis revealed that the reduction was caused by a decrease in the affinity rather than one in the maximal binding capacity. The specificity of the binding sites thereby shifted to be more nonspecific without affecting the order of the relative affinities among PGs for the binding sites. These results suggest that the carbohydrate moieties on PG receptor proteins of the brain are essential for the expression of their binding activities. PMID- 1309290 TI - Catalytic properties of the inorganic pyrophosphatase in rat liver mitochondria. AB - Intact rat liver mitochondria have very low hydrolytic activity, if any, toward exogenous pyrophosphate. The activity can be unmasked by making mitochondria permeable to PPi by toluene treatment or disrupting them with detergents or ultrasound, indicating that the active site of pyrophosphatase is located in the matrix. Initial rates of PPi hydrolysis by toluene-permeabilized mitochondria and purified pyrophosphatase were found to depend in a similar manner on PPi and Mg2+ concentrations. The simplest model consistent with the data in both cases implies that the reaction proceeds through two pathways and requires MgPPi as the substrate and, at least, one Mg2+ ion as the activator. In the presence of 0.4 mM Mg2+ (physiological concentration), the inhibition constant for Ca2+ is 12 microM and the enzyme activity is, at least, 50% maximal. The results suggest that the activity of pyrophosphatase in mitochondria is high enough to keep free PPi concentration at a level close to that at equilibrium. PMID- 1309291 TI - Reaction of the nucleotide analogue 2-[(4-bromo-2,3-dioxobutyl)thio]adenosine 2',5'-bisphosphate at the coenzyme site of wild-type and mutant NADP(+)-specific glutamate dehydrogenases from Salmonella typhimurium. AB - Wild-type glutamate dehydrogenase (EC 1.4.1.4) from Salmonella typhimurium reacts at 25 degrees C in 0.1 M phosphate buffer, pH 7, with the nucleotide analogue 2 [(4-bromo-2,3-dioxobutyl)thio]-adenosine 2',5'-bisphosphate (2-BDB-TA 2',5'-DP) to give 78% inactivation. Protection against inactivation was achieved with NADPH, indicating that modification occurred in the region of the coenzyme binding site. After reaction of the enzyme with 2-BDB-TA 2',5'-DP, the dioxo moiety of the bound reagent was reduced with [3H]NaBH4. The radioactive peptide which corresponds to the sequence Leu282-Cys283-Glu284-Ile285-Lys286 was isolated by HPLC from tryptic digests of inactive modified enzyme but was absent in digests of active enzyme modified in the presence of NADPH. Mutant enzyme E284Q was 64% inactived by 2-BDB-TA 2',5'-DP and modification of the corresponding Leu282-Lys286 peptide was found, while neither mutant enzyme C283I nor C283I:E284Q was inactivated by the nucleotide analogue and no corresponding radioactive peptides were found. These results show that cysteine-283 is the target of the reagent and is located near the coenzyme binding site. The nucleotide analogue 2-[(4-bromo-2,3-dioxobutyl)thio]-1,N6-ethenoadenosine 2',5' bisphosphate (2-BDB-T epsilon A 2',5'-DP) has also been shown to react with cysteine-283 (L. Haeffner-Gormley et al., 1991, J. Biol. Chem. 266, 5388-5394). However, the predominant form of the Leu282-Lys286 peptide after reaction with 2 BDB-TA 2',5'-DP contained only 0.17 mol tritium/mol leucine, whereas the 2-BDB-T epsilon A 2',5'-DP-modified peptide contained 1.80 mol tritium/mol leucine; these results indicate that the reaction product of 2-BDB-T epsilon A 2',5'-DP retains two reducible carbonyl groups while these are not available in the product of 2 BDB-TA 2',5'-DP. It is suggested that cysteine-283 reacts primarily at a carbonyl group of 2-BDB-TA 2',5'-DP to form a thiohemiacetal derivative, while it reacts at the methylene group of 2-BDB-T epsilon A 2',5'-DP with displacement of bromide. Both nucleotide analogues also yielded, in small amount, a crosslinked peptide containing the sequences 282-286 and 299-333, indicating proximity between these regions in the native structure. PMID- 1309292 TI - Direct identification of lysine-33 as the principal cationic center of the omega amino acid binding site of the recombinant kringle 2 domain of tissue-type plasminogen activator. AB - We have generated site-specific mutants of the kringle 2 domain of tissue-type plasminogen activator [( K2tPA]) in order to identify directly the cationic center of the protein that is responsible for its interaction with the carboxyl group of important omega-amino acid effector molecules, such as epsilon-amino caproic acid (EACA). Molecular modeling of [K2tPA], docked with EACA, based on crystal structures of the kringle 2 region of prothrombin and the kringle 4 domain of human plasminogen, clearly shows that Lys33 is the only positively charged amino acid in [K2tPA] that is sufficiently proximal to the carboxyl group of the ligand to stabilize this interaction. In order to examine directly the importance of this particular amino acid residue in this interaction, we have constructed, expressed, and purified three recombinant (r) mutants of [K2tPA], viz., Lys33Thr, Lys33Leu, and Lys33Arg, and found that only the last variant retained significant ability to interact with EACA and several of its structural analogues at neutral pH. In addition, another mutated r-[K2tPA], i.e., Lys33His, interacts very weakly with omega-amino acids at neutral pH and much more strongly at lower pH values where His33 would be expected to undergo protonation. This demonstrates that any positively charged amino acid at position 33 satisfies the requirement for mediation of significant bindings to this class of molecules. Since, in other kringles, positively charged residues at amino acid sequence positions homologous to Lys68, Arg70, and Arg71 of [K2tPA] have been found to participate in kringle interactions with EACA-like compounds, we have also examined the binding of EACA, and some of its analogues, to three additional r [K2tPA] variants, i.e., Lys68Ala, Arg70Ala, and Arg71Ala. In each case, binding of these omega-amino acids to the variant kringles was observed, with only the Lys68Ala variant showing a slightly diminished capacity for this interaction. These investigations provide clear and direct evidence that Lys33 is the principal cationic site in wild-type r-[K2tPA] that directly interacts with the carboxyl group of omega-amino acid effector molecules. PMID- 1309293 TI - Structure-activity relationship of minoxidil analogs as inhibitors of lysyl hydroxylase in cultured fibroblasts. AB - The structural features that confer upon minoxidil the ability to suppress lysyl hydroxylase activity in human skin fibroblasts were investigated. Substitution of the amino group in position 2 or 6 of the pyrimidine ring with a methyl group had no significant effect on the inhibitory activity of minoxidil, whereas substitution of both amino groups with methyl groups resulted in a complete loss of inhibitory activity. Together, these observations indicate that only one of the two amino groups ortho to the nitroxide oxygen is essential for the enzyme suppressing effect of minoxidil. Derivatives of minoxidil formed by hydroxylation at position 3 or 4 of the piperidine ring were as active as the parent compound in suppressing lysyl hydroxylase activity. However, replacement of the piperidinyl group in position 4 of the pyrimidine ring with a pyrrolidinyl, morpholinyl, or N-methylpiperazinyl group resulted in loss of inhibitory activity, demonstrating that the piperidinyl group para to the nitroxide oxygen is essential for the enzyme-suppressing effect of minoxidil. Removing the nitroxide oxygen from position 1 of the pyrimidine ring resulted in a partial loss of the specificity of minoxidil for suppression of lysyl hydroxylase activity. The results indicate that distinct structural elements determine the enzyme-suppressing effect and the antihypertensive effect of minoxidil. PMID- 1309294 TI - Polycyclic aromatic hydrocarbon quinones may be either substrates for or irreversible inhibitors of the human placental NAD-linked 15-hydroxyprostaglandin dehydrogenase. AB - Under aerobic conditions, 9,10-phenanthrenequinone and 5,6-chyrsenequinone undergo oxidation-reduction cycling in the presence of NADH and the NAD-linked 15 hydroxyprostaglandin dehydrogenase. This results in the formation of potentially hazardous semiquinones, the superoxide anion, and H2O2. Superoxide dismutase inhibits this cycling by destroying the free radical chain propagator, the superoxide anion. Four other polycyclic aromatic hydrocarbon quinones are not substrates of the enzyme and they cause it to undergo a time-dependent inactivation. This presumably results from alkylation of the enzyme. Glutathione fully protects the enzyme against inactivation by 1,2-naphthoquinone but is only partially effective against 7,8-benzo[a]pyrenequinone. These results suggest that in tissues which contain the NAD-linked 15-hydroxyprostaglandin dehydrogenase some polycyclic aromatic hydrocarbon quinones might produce deleterious effects by undergoing redox cycling. Others might cause such effects by irreversibly inhibiting the enzyme which catalyzes the first step in prostaglandin catabolism. PMID- 1309296 TI - The effect of orthovanadate on phosphoinositide metabolism in NIH 3T3 fibroblasts. AB - Orthovanadate is an agent known to stimulate cell growth and mimic insulin action. The effects of this compound on phosphoinositides in NIH 3T3 cells were examined. Both 100 and 1000 microM orthovanadate were found to increase the cellular content of inositol phosphate secondary to the activation of phosphatidylinositol-specific phospholipase C (PtdIns-PLC). The time course, dependence on orthovanadate concentration, and sensitivity to the isoflavone genistein were similar for orthovanadate-induced accumulation of inositol phosphate and protein tyrosine phosphate, indicating that there is a correlation between cellular protein tyrosine phosphate levels and PtdIns-PLC activity. Increased phosphatidylinositol phosphate (PtdInsP) content also occurred when cells were incubated with orthovanadate and appeared to result from the activation of PtdIns kinase. This effect was not correlated with cellular protein tyrosine phosphate content. Hence, orthovanadate is shown to affect phosphoinositide metabolism at a minimum of two sites by both tyrosine phosphate dependent and -independent mechanisms. PMID- 1309295 TI - Mechanism of benzo[a]pyrene-induced Cyp1a-1 gene expression in mouse Hepa 1c1c7 cells: role of the nuclear 6 s and 4 s proteins. AB - Treatment of wild-type (wt) aryl hydrocarbon (Ah)-responsive mouse Hepa 1c1c7 cells with benzo[a]pyrene (B[a]P) caused a concentration-dependent induction of ethoxyresorufin O-deethylase (EROD) activity. In contrast, B[a]P was inactive as an inducer in Ah nonresponsive class 1 and class 2 mutant cell lines. In parallel experiments, the nuclear fractions from wt cells treated with 10(-7) M [3H]B[a]P contained both the 4 s carcinogen binding protein and the 6 s (Ah receptor) complexes, whereas only the 4 s complex was present in the nuclear fraction of the class 2 mutant cells. The results obtained from cotreatment of wt Hepa 1c1c7 cells with 10(-6) or 10(-7) M B[a]P and 5 x 10(-7) or 10(-7) M 6-methyl-1,3,8 trichlorodibenzofuran (MCDF) showed that MCDF inhibited the induction of EROD activity and Cyp1a-1 mRNA levels by B[a]P. Moreover, using 10(-7) M [3H]B[a]P and unlabeled MCDF, it was shown that MCDF not only inhibited the induction response but also caused a concentration-dependent decrease in levels of the nuclear 6 s complex but not the 4 s complex. In contrast, in situ competition studies with unlabeled 10(-6) M benzo[ghi]-perylene (B[ghi]P) resulted in the elimination of the nuclear [3H]B[a]P 4 s complex (but not the 6 s complex); however, the EROD activity and Cyp1a-1 mRNA levels in cells treated with 10(-7) M B[a]P in the presence or absence of 10(-6) M B[ghi]P were not significantly different. These results indicate that the 4 s binding protein is not required for the induction of Cyp1a-1 gene expression in Hepa 1c1c7 cells and suggest that B[a]P and 2,3,7,8 tetrachlorodibenzo-p-dioxin induce Cyp1a-1 gene expression via a common mechanism which involves binding to the Ah receptor. PMID- 1309297 TI - Effect of carboxyl terminal truncation on the tyrosine kinase activity of the epidermal growth factor receptor. AB - The carboxyl terminal domain of the epidermal growth factor receptor (EGFR) is an important regulatory region in mediating the tyrosine kinase-dependent biological effects of EGF. The effect of a 164-amino-acid carboxyl deletion of the EGFR or the EGFR cytoplasmic kinase domain on in vitro tyrosine kinase activity was assessed. C'-terminal truncation of the EGFR resulted in dependence on Mn2+ for full activity. The EGFR kinase domain (kd EGFR) and the C'-terminally truncated kinase domain (kd c'1022 EGFR) also exhibited a strong preference for Mn2+ compared to Mg2+, with kd c'1022 EGFR being completely inactive in the presence of Mg2+ alone. Sphingosine or ammonium sulfate specifically activated both kd EGFR and kd c'1022 EGFR. EGFR and c'1022 EGFR displayed similar EGF-stimulated in vitro tyrosine kinase activities; however, kd EGFR was 5- to 10-fold more active in vitro than kd c'1022 EGFR. Thus, the regulatory contribution of the C' terminus is most evident when the EGFR ligand binding domain is removed. These results indicate that an intact EGFR C'-terminus is necessary for the protein to assume a fully active conformation. PMID- 1309298 TI - NADH-dependent methemoglobin reductase from the obligate aerobe Vitreoscilla: improved method of purification and reexamination of prosthetic groups. AB - The NADH-dependent methemoglobin reductase from the bacterium Vitreoscilla was purified using hydrophobic chromatography on a phenyl-Sepharose column. The new procedure resulted in a purer protein and increased the overall yield of the enzyme by a factor of approximately three. The active site of the enzyme was investigated by ultraviolet/visible, fluorescence, Mossbauer, and electron paramagnetic resonance spectroscopy (EPR) at 9.4 GHz. Prosthetic group analysis revealed the presence of one FAD per active enzyme molecule but no iron in contrast to earlier reports. The NADH-methemoglobin reductase activity of the pure enzyme was in the range of 1.1-1.25 units; its electronic and fluorescence spectra were typical of metal-free flavoproteins. No EPR signals were detected between 5 and 150 K over a field range 0.05-0.5 T, and there was no Mossbauer signal, consistent with the absence of iron. Methemoglobin reductase from Vitreoscilla was reduced by dithionite, NADH, and deazaflavin/EDTA upon illumination. The main species observed during these anaerobic oxidation reduction experiments was the blue semiquinone radical with an EPR signal at g = 2.005, linewidth 1.5 mT. The fully reduced state of the enzyme, FlredH3, was also observed in the reaction with NADH. The reduction was fully reversible with ferricyanide. The observations reported here are consistent with a redox enzyme interacting both with a two-electron donating agent such as NADH and a one electron accepting center such as the Fe(III)/Fe(II) couple of Vitreoscilla hemoglobin. PMID- 1309299 TI - The role of superoxide radical in chromium (VI)-generated hydroxyl radical: the Cr(VI) Haber-Weiss cycle. AB - To understand the role of the superoxide (O-2) radical in chromate-related genotoxicity, we investigated whether Cr(VI) can catalyze the Haber-Weiss cycle in vitro: O-2 + Cr(VI)----Cr(V) + O2 Cr(V) + H2O2----Cr(VI) + .OH + OH-. ESR and spin trapping techniques were utilized to monitor the O-2 (produced using xanthine/xanthine oxidase), .OH, and Cr(V) species. Superoxide dismutase as well as catalase inhibited the .OH radical radical formation, attesting to the direct involvement of O-2 and H2O2 in the process. ESR measurements also provided direct evidence for the formation of Cr(V). Kinetic measurements were consistent with the role of Cr(V) and H2O2 as intermediates in .OH formation. These results indicate that in cellular media, especially during chromate phagocytosis, the O-2 radical can become a significant source of .OH radicals and hence a significant factor in the biochemical mechanism of cellular damage due to Cr(VI) exposure. PMID- 1309300 TI - Phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, and the phosphoinositol sphingolipids are found in the plasma membrane and stimulate the plasma membrane H(+)-ATPase of Saccharomyces cerevisiae. AB - Several plasma membrane phospholipids have been studied for their ability to modulate the activity of the plasma membrane H(+)-ATPase of Saccharomyces cerevisiae. We show here that phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2), and/or the phosphatidylinositol and PIP kinases are localized primarily in the plasma membrane. Previous in vivo studies with S. cerevisiae have shown that large, rapid, and reversible changes occur in the levels of PIP and PIP2 congruent with changes in cellular ATP levels. We demonstrate here that isolated plasma membranes exhibit the same changes in PIP and PIP2 content when they are supplied with or washed free of ATP. Using a mixed micellar assay we systematically studied the efficacy of the plasma membrane lipids in sustaining the activity of the plasma membrane H(+)-ATPase. We demonstrate for the first time that a number of plasma membrane glycerophospholipids effectively stimulate the ATPase, including PIP, PIP2, and cardiolipin. Phosphoinositol-containing sphingolipids, major components of the plasma membrane, are also shown to stimulate the ATPase at significantly lower levels than the glycerophospholipids and must also be considered as important effectors in vivo. PMID- 1309301 TI - Differentiation markers in hemangiopericytoma. AB - Normal pericytes were found to express factor XIIIa (F-XIII) and histocompatibility antigen HLA-DR. These markers were studied in 15 hemangiopericytomas (HPC) and 16 other tumors with an HPC-like pattern. A subpopulation of tumor cells expressing F-XIII and HLA-DR antigens was a constant feature of HPC and supported their pericytic origin. Meningeal HPC did not differ in phenotype from peripheral soft tissue HPC. Most tumors with an HPC-like pattern (including synovial sarcomas, malignant schwannomas, leiomyosarcomas, and liposarcomas) were negative for F-XIII and HLA-DR. Malignant fibrous histiocytomas, however, invariably contained a subpopulation expressing these antigens. Therefore, F-XIII can be considered as a marker of fibrohistiocytic differentiation in HPC. Individual tumor cells in HPC occasionally were positive for factor VIII-related antigen (F-VIII-R-Ag), suggesting that the spectrum of differentiation in HPC may include the endothelial cell line. The differentiation characteristics of HPC support the concept that pericytes are primitive cells that may act as precursors to other mesenchymal cells. PMID- 1309302 TI - The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes. AB - A retrospective study of 33 patients with cystosarcoma phyllodes was done. Eight of these patients had metastases, and the clinical and histologic criteria predicting the development of metastases were examined. The most reliable predictor was the presence of stromal overgrowth; this appears to be necessary for metastasis to occur. Other useful indicators of clinical behavior were the degree of mitotic activity, nuclear pleomorphism, and infiltrating margins. Based on these data and a literature review, the authors suggest close follow-up of patients whose primary tumors contain areas of stromal overgrowth because, in all series combined, the risk of metastatic spread in such patients was 72% within 5 years. Among these high-risk patients, local recurrence is another indication that metastasis is likely. PMID- 1309303 TI - Cisplatin-induced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity. AB - The authors prospectively evaluated the effects of three different schedules of cisplatin (DDP) administration in 60 patients with advanced epithelial ovarian cancer. The individual total dose of DDP was 450 mg/m2 in all three groups, and the anti-cancer response at the end of treatment was similar for the different regimens. The clinical and neurophysiologic results confirmed that axonal sensory neuropathy occurred after the standard administration of DDP (75 mg/m2 in 3-week cycles) and probably not only the peripheral, but also the central sensory pathway, was involved. Although the total dose of the drug was identical, the two less conventional schedules were less neurotoxic. These results suggest that not only the total-dose intensity, but also the single-dose intensity are relevant in the onset of DDP-induced sensory neuropathy; therefore, the use of less neurotoxic schedules may prevent or reduce sensory nerve damage. PMID- 1309304 TI - Mucinous carcinoma of the ovary. Pathologic prognostic factors. AB - Thirty-four ovarian mucinous carcinomas defined by nuclear stratification in excess of three layers (noninvasive mucinous carcinoma, NIMC) or stromal invasion (invasive mucinous carcinoma, IMC) were examined to define prognostic indicators. Twenty-two patients had NIMC (Stage I, 15; Stage II, 1; Stage III, 5; and Stage IV, 1). Twelve patients had IMC (Stage I, one; Stage II, one; and Stage III, ten). Fifteen patients died, ten with IMC and five with NIMC (mean survival, 16.7 months). Nineteen patients survived, two with IMC and 17 with NIMC (mean follow up, 12 years). Ten of the 12 patients with IMC who died had Stage III disease. Five of the 22 patients with NIMC who died included four with Stage III and one with Stage I disease. Among patients who died, those with IMC tended to have a shorter mean survival than those with NIMC. No differences among groups were identified with respect to nuclear grade, mitotic activity, percentage of tumor displaying more than three cell layers, or amount of invasion. In ovarian mucinous carcinoma, clinical stage and stromal invasion are the most important prognostic variables, and they are interrelated. Stage I NIMC rarely pursues an aggressive course. PMID- 1309305 TI - Failure to detect human papillomavirus DNA in extramammary Paget's disease. AB - Ten genital skin specimens, biopsy proven to be Paget's disease, were examined by human papillomavirus (HPV) in situ hydridization in an effort to detect DNA of HPV types 6, 11, 16, 18, 31, 33, and 35. All ten specimens showed no evidence of DNA of these HPV types. Extra-mammary Paget's disease is probably not a result of infection with HPV types 6, 11, 16, 18, 31, 33, or 35. PMID- 1309306 TI - Novel tumor necrosis factor toxic effects. Pulmonary hemorrhage and severe hepatic dysfunction. AB - Recombinant human tumor necrosis factor is an investigational antitumor agent currently undergoing clinical trials. Previous reports of pulmonary and hepatic toxicities include mild reversible decline in pulmonary diffusing capacity and mild elevation of bilirubin and transaminases. This report describes two novel toxicities in patients receiving their first intravenous dose of tumor necrosis factor: pulmonary hemorrhage and severe hepatic dysfunction. These patients received no other antitumor therapy for at least 4 weeks before tumor necrosis factor treatment and no additional antitumor therapy concomitant with tumor necrosis factor. An analysis of the possible pathogenesis is presented. PMID- 1309307 TI - Immunoglobulin A against viral capsid antigen of Epstein-Barr virus and indirect mirror examination of the nasopharynx in the detection of asymptomatic nasopharyngeal carcinoma. AB - To evaluate the efficacy of population screening for early stage nasopharyngeal carcinoma (NPC) in southern China, the authors recruited 42,048 and 10,402 apparently healthy subjects residing in a high incidence and a low incidence area, respectively; all subjects were between the ages of 30 and 59 years. The subjects' serum specimens were tested for immunoglobulin (Ig) A antibody against viral capsid antigen (IgA/VCA) of Epstein-Barr virus (EBV). Of the subjects from the high incidence area, 2823 were found to be seropositive. In follow-up, they had yearly examinations of the nasopharynx by indirect mirror with or without biopsy; 41 were found to have histologically confirmed asymptomatic NPC during the first 2 years of follow-up. The tumors in most of these cases were localized and were at earlier stages than tumors of symptomatic cases of NPC seen in the same region before the screening. The yearly indirect mirror examination of the nasopharynx seems to have effectively identified most of the tumors at the stage of asymptomatic disease. The risk of harboring NPC was found to be different among the different sex and age subgroups of seropositive individuals. By limiting such screening to those who are at exceedingly high risk, the cost of the screening can be kept within the spending of the public health authority, and the effectiveness of the screening also is improved. PMID- 1309308 TI - Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K. AB - The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK 4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects. PMID- 1309309 TI - A clinical and radiologic study of primary liver cancer associated with extrahepatic primary cancer. AB - In a consecutive series of 393 patients with excised and pathologically proven primary liver cancer (PLC)--including 374 hepatocellular carcinomas (HCC), nine cholangiocellular carcinomas (CCC), and ten mixed type of HCC and CCC--33 patients (8.4%) had one or two other malignancies in the extrahepatic organ(s). Of these, 29 had double cancers and four, triple cancers. This was synchronous in 11 patients, metachronous in 20 (including 18 with double cancers and two with triple cancers) and synchronous and metachronous in two with triple cancers. Metachronous cancer was found in 21 patients 1 year before hepatectomy for PLC and in three patients, 1 year after hepatectomy. The median age of PLC patients with multiple primary cancer (MPC) was 63.6 +/- 6.9 years; this was significantly greater than that of PLC patients without MPC (P less than 0.01). The associated cancer was gastric cancer in 11 patients (29.7%), colorectal cancer in six, pharyngeal cancer in four, and other cancers in ten different organs in 16. Thirteen of 22 patients had a history of blood transfusion. The incidence of liver cirrhosis in PLC associated with MPC (57.6%) was significantly lower than that without MPC (82.8%, P less than 0.01). The differential diagnosis of PLC from liver metastasis was possible retrospectively in 78.6% using sonograms, 79.3% using computed tomograms, and 91.3% using angiograms. The survival rates of patients with PLC with (n = 33) and without (n = 299) MPC who had undergone hepatectomy were 97.0% and 85.4% at 1 year, 55.5% and 59.5% at 3 years, and 40.5% and 40.1% at 5 years, respectively. There was no significant difference between the survival rates of those who underwent operations for PLC and extrahepatic primary cancer(s) synchronously and metachronously. PMID- 1309311 TI - Prognostic significance of the expression of ras oncogene product in non-small cell lung cancer. AB - The clinical significance of ras oncogene expression in non-small cell lung cancer was evaluated in 116 surgically treated patients. Archival paraffin sections of the tumors were analyzed immunohistochemically using anti-ras p21 monoclonal antibody (MoAb) rp-35, and p21 staining was correlated with clinicopathologic parameters and survival. Positive reactions (+ and ++) were observed in 72.5% of the adenocarcinomas and 55.6% of the squamous cell carcinomas studied. The T1 tumors showed a ++ reaction less frequently than T2 and T3 tumors (P less than 0.05). Stage I tumors also were less reactive with MoAb rp-35 than tumors in more advanced stages (P less than 0.05). Survival analysis showed that patients with p21-negative tumors had significantly longer survival times (a 5-year survival rate of 64.1%) than those with p21 + tumors (38.0%, P less than 0.05) or those with p21 ++ tumors (11.5%, P less than 0.005). The significant correlation between p21 staining and patient survival was independent of histologic type, stage of disease, tumor or node status, and the resectability of tumors. On Cox's multivariate analysis, p21 staining was a major and independent prognostic determinant of survival. These results suggest that enhanced ras p21 expression may be one of the important biologic and clinical markers indicating the malignant potential of non-small cell lung cancer. PMID- 1309310 TI - Paraneoplastic Cushing's syndrome as an adverse prognostic factor in patients who die early with small cell lung cancer. AB - The potential role of paraneoplastic Cushing's syndrome (CS) was assessed on the clinical course of patients with small cell lung cancer. A retrospective comparison was done of complications and survival rates according to the presence or absence of CS in patients with small cell lung cancer who died within 90 days of initial administration of chemotherapy. The setting was a comprehensive cancer center. Eleven patients with clinical and/or biochemical features of CS were identified from among 90 patients who presented between 1979 and 1989 with previously untreated small cell lung cancer. The group with CS and the control patients were compared in terms of clinicopathologic prognostic factors, treatment, and outcome. Patients with CS were comparable to the control patients in all prognostic factors, including tumor stage and cancer treatment. Eighty-two percent of patients with CS (nine of 11) died within 14 days of initiation of chemotherapy compared with 25% of the control patients (19 of 77). The median survival from initiation of chemotherapy was 12 days for the 11 patients with CS and 27 days for the 77 control patients. In 45% of the patients with CS (five of 11), death was attributed to opportunistic fungal or protozoal infection compared with 8% of control patients (six of 77). Paraneoplastic CS is a previously unrecognized adverse prognostic factor for patients with small cell lung cancer. Those with both small cell lung cancer and CS have severe opportunistic infections soon after the initiation of chemotherapy, leading to clinical deterioration and death before antineoplastic benefit from chemotherapy can be achieved. Biochemical control of CS for at least 1 to 2 weeks before initiation of chemotherapy may ameliorate the poor prognosis. PMID- 1309312 TI - A flow cytometric study of non-small cell lung cancer classified as T1N0. AB - Surgical resection currently offers the best chance for cure of non-small cell lung cancer but its efficacy is limited by subsequent tumor recurrence. Even the most favorable cancers (T1N0 tumors) recur 20% to 30% of the time within 5 years and there is currently no way to anticipate precisely which tumors will recur. To test whether DNA flow cytometric study might be useful in this regard, the authors performed a retrospective case-control study of 102 tumors (51 recurrent cases and 51 controls) from a prospective registry of patients with completely resected, meticulously staged T1N0 non-small cell carcinomas. Unbiased relative hazard ratios of recurrence were estimated for ploidy and proliferative rate, as well as for tumor histologic type and clinical variables. Ploidy abnormalities were slightly more common among cases (67%) than controls (57%) but this difference was not statistically significant. Estimation of proliferative rates was possible for 85 tumors but there was no significant difference between cases and controls and proliferative rates were not prognostic of recurrence. In multivariate analyses, the observed predictive value for each of the flow cytometric parameters was modest at best and smaller than that seen for tumor histologic type. These results suggest that flow cytometric analysis has limited value in guiding management of patients with early stage non-small cell carcinoma. PMID- 1309313 TI - Developmental changes in the beta-adrenergic modulation of calcium currents in rabbit ventricular cells. AB - We studied the developmental changes in the beta-adrenergic modulation of L-type calcium current (ICa) in enzymatically isolated adult (AD) and newborn (NB, 1-4 day-old) rabbit ventricular cells using the whole-cell patch-clamp method. ICa was measured as the peak inward current at a test potential of +15 mV by applying a 180-450-msec pulse from a holding potential of -40 mV with Cs(+)-rich pipettes and a K(+)-free bath solution at room temperature. In control, ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells (5.5 +/- 0.2 [mean +/- SEM] pA/pF, n = 65) than in NB cells (2.6 +/- 0.1 pA/pF, n = 60). Isoproterenol (ISO, 1 nM-30 microM) increased ICa in a dose dependent manner for both groups. The maximal effect (Emax) of ISO, expressed as percent increase in ICa over control levels, and the concentration for one half of the maximal effect (EC50) were 203% and 51 nM, respectively, for AD cells and 111% and 81 nM, respectively, for NB cells. The effect of ISO (1 microM) on ICa was decreased as the test potential was increased from -10 to +40 mV. However, the ratio of the percent increase in ICa for AD versus NB cells was almost constant (2.09-2.45) at each test potential. Dose-response curves of forskolin (FOR, 0.3-50 microM) gave Emax and EC50 of 268% and 0.74 microM, respectively, for AD cells and 380% and 1.15 microM, respectively, for NB cells. After stimulating ICa by 10 microM ISO, the addition of 10 microM FOR produced a further increase in ICa of only 12 +/- 2% in AD cells (n = 4) but a further increase of 140 +/- 41% in NB cells (n = 6). FOR (10 microM) did not produce any increase in ICa for AD and NB cells after stimulating ICa by intracellular application of 200 microM cAMP. ICa density stimulated by 10 microM ISO (17.8 +/- 1.1 pA/pF, n = 7), 10 microM FOR (21.0 +/- 1.3 pA/pF, n = 8), or 200 microM cAMP (18.0 +/- 1.3 pA/pF, n = 5) was equivalent in AD cells, whereas ICa density stimulated by 10 microM ISO (5.8 +/- 0.6 pA/pF, n = 9) was significantly lower than that stimulated by either 10 microM FOR (13.8 +/- 1.5 pA/pF, n = 7) or 200 microM cAMP (13.4 +/- 0.7 pA/pF, n = 7) in NB cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309314 TI - Behavior of genes directly injected into the rat heart in vivo. AB - Gene transfer can be achieved in the adult rat heart in vivo by direct injection of plasmid DNA. In this report we define the spatial and temporal limits of reporter gene expression after a single intracardiac injection. pRSVCAT (100 micrograms), in which the Rous sarcoma virus long terminal repeat is fused to the chloramphenicol acetyltransferase reporter gene, and p alpha MHCluc (100 micrograms), in which the alpha-cardiac myosin heavy chain promoter is fused to the firefly luciferase gene, were injected into hearts, and reporter gene activities were assayed at various times. Both chloramphenicol acetyltransferase and luciferase were detectable in 100% of the rats from 1 to 7 days, in 60% of the rats from 17 to 23 days, and in 30% of the rats from 38 to 60 days after injection. Reporter gene activity was largely limited to a 1-2-mm region of the ventricle surrounding the injection site. Closed circular DNA was far more effective than linear DNA in transfecting cells in vivo. The relative strengths of three different promoters, Rous sarcoma virus long terminal repeat, alpha myosin heavy chain, and alpha 1-antitrypsin, all fused to the luciferase reporter gene were determined. The constitutive viral promoter was approximately 20-fold more active than the cardiac-specific cellular promoter, and the liver-specific cellular promoter was not active at all in the cardiac environment. Thus, direct injection of genes into the heart offers a simple and powerful tool with which to assess the behavior of genes in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309315 TI - Enhancement of rabbit cardiac sodium channels by beta-adrenergic stimulation. AB - Voltage-dependent sodium channels from a variety of tissues are known to be phosphorylated by the cAMP-dependent protein kinase, protein kinase A. However, the functional significance of sodium channel phosphorylation is not clearly understood. Using whole-cell voltage-clamp techniques, we show that sodium currents (INas) in rabbit cardiac myocytes are enhanced by isoproterenol (ISO). This enhancement of INa by ISO 1) is holding potential dependent, 2) can be mimicked by forskolin and dibutyryl cAMP, and 3) is accompanied by an increase in the rate of Na+ channel inactivation. In single-channel, inside-out patch experiments, the catalytic subunit of protein kinase A also enhances INa and increases the rate of inactivation, suggesting that cardiac Na+ channel phosphorylation may be physiologically important. Addition of the protein kinase A inhibitor to the pipette solution in whole-cell experiments blocks the stimulatory effect of forskolin without blocking the effect of ISO, suggesting that ISO also enhances INa through a cAMP-independent pathway. To determine if ISO may stimulate INa through a direct G protein pathway, single channels were recorded in the presence of the Gs-activating GTP analogue, GTP gamma S, and the stimulatory G protein subunit, Gs alpha. Both of these agents enhanced INa without affecting the rate of Na+ channel inactivation. These results suggest that ISO enhances rabbit cardiac INa through a dual (direct and indirect) G protein regulatory pathway. PMID- 1309316 TI - Role of nitric oxide in reactive hyperemia of the guinea pig heart. AB - To evaluate the role of nitric oxide (NO) in the flow response after brief coronary arterial occlusion, NO formation by the isolated guinea pig heart was assessed by a specific difference spectrophotometric assay. Release of NO under basal conditions was 121.8 +/- 10.5 pmol x min-1 and increased to 211.1 +/- 16.8 pmol x min-1 after 60 seconds of coronary occlusion. Simultaneously, release of cGMP and adenosine increased by 87% and 652%, respectively. The kinetics of NO release paralleled the reactive hyperemic flow response. Inhibition of NO synthesis with nitro-L-arginine methyl ester (L-NAME, 30 microM) significantly reduced basal flow and attenuated reactive hyperemia, flow repayment, and repayment ratio. L-NAME decreased release of cGMP but significantly increased adenosine release under basal conditions and during reactive hyperemia. Oxyhemoglobin (5 microM) potentiated the effects of L-NAME. The stereoisomer nitro-D-arginine methyl ester was ineffective. Our results suggest 1) NO is an important regulator of coronary flow during reactive hyperemia as well as under basal flow conditions and 2) the significance of the increased adenosine release when NO synthesis is inhibited remains to be determined. PMID- 1309317 TI - An electron-microscopic study of smooth muscle cell dye coupling in the pig coronary arteries. Role of gap junctions. AB - Arterial smooth muscles behave like a syncytium, since they are electrically coupled. It is generally assumed that electrical coupling and dye coupling are mediated by gap junctions. No gap junctions could be detected by transmission electron microscopy in media of coronary arteries. We looked for the presence of gap junction protein in vascular smooth muscle by immunohistochemistry with light microscopy. Immunohistologically detectable connexin is expressed by smooth muscle cells of the media of pig coronary arteries, where staining occurs as a discrete punctation. We investigated the dye coupling in strips of pig coronary artery. The fluorescent dye lucifer yellow was microiontophoretically injected into a smooth muscle cell through an intracellular microelectrode. The dye was visualized on the entire strip, then on semithin sections with a fluorescence microscope, and at the ultrastructural level by using an anti-lucifer yellow antibody revealed by the protein A-gold technique. In all the tissues examined, the cells were dye-coupled. We conclude that in arterial media the smooth muscle cells are dye-coupled, despite the absence of detectable gap junctions by transmission electron microscopy, and suggest that dye coupling could occur via isolated gap junction channels. PMID- 1309318 TI - Kappa and delta opioid receptor stimulation affects cardiac myocyte function and Ca2+ release from an intracellular pool in myocytes and neurons. AB - We investigated the effects of mu, delta, and kappa opioid receptor stimulation on the contractile properties and cytosolic Ca2+ (Cai) of adult rat left ventricular myocytes. Cells were field-stimulated at 1 Hz in 1.5 mM bathing Ca2+ at 23 degrees C. The mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10(-5) M) had no effect on the twitch. The delta-agonists methionine enkephalin and leucine enkephalin (10(-10) to 10(-6) M) and the kappa-agonist (trans-(dl)-3,4-dichloro-N methyl-N-[2-(1-pyrrolidinyl)cyclo-hexyl]- benzeneacetamide)methanesulfonate hydrate (U-50,488H; 10(-7) to 2 x 10(-5) M) had a concentration-dependent negative inotropic action. The sustained decrease in twitch amplitude due to U 50,488H was preceded by a transient increase in contraction. The effects of delta and kappa-receptor stimulation were antagonized by naloxone and (-)-N-(3-furyl methyl)-alpha-normetazocine methanesulfonate, respectively. In myocytes loaded with the Ca2+ probe indo-1, the effects of leucine enkephalin (10(-8) M) and U 50,488H (10(-5) M) on the twitch were associated with similar directional changes in the Cai transient. Myofilament responsiveness to Ca2+ was assessed by the relation between twitch amplitude and systolic indo-1 transient. Leucine enkephalin (10(-8) M) had no effect, whereas U-50,488H (10(-5) M) increased myofilament responsiveness to Ca2+. We subsequently tested the hypothesis that delta and kappa opioid receptor stimulation may cause sarcoplasmic reticulum Ca2+ depletion. The sarcoplasmic reticulum Ca2+ content in myocytes and in a caffeine sensitive intracellular Ca2+ store in neurons was probed in the absence of electrical stimulation via the rapid addition of a high concentration of caffeine from a patch pipette above the cell. U-50,488H and leucine enkephalin slowly increased Cai or caused Cai oscillations and eventually abolished the caffeine triggered Cai transient. These effects occurred in both myocytes and neuroblastoma-2a cells. In cardiac myocyte suspensions U-50,488H and leucine enkephalin both caused a rapid and sustained increase in inositol 1,4,5 trisphosphate. Thus, delta and kappa but not mu opioids have a negative inotropic action due to a decreased Cai transient. The decreased twitch amplitude due to kappa-receptor stimulation is preceded by a transient increase in contractility, and it occurs despite an enhanced myofilament responsiveness to Ca2+. The effects of delta and kappa opioids appear coupled to phosphatidylinositol turnover and, at least in part, may be due to sarcoplasmic reticulum Ca2+ depletion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309319 TI - Basement membrane proteins: structure, assembly, and cellular interactions. AB - Basement membranes are thin layers of a specialized extracellular matrix that form the supporting structure on which epithelial and endothelial cells grow, and that surround muscle and fat cells and the Schwann cells of peripheral nerves. One common denominator is that they are always in close apposition to cells, and it has been well demonstrated that basement membranes do not only provide a mechanical support and divide tissues into compartments, but also influence cellular behavior. The major molecular constituents of basement membranes are collagen IV, laminin-entactin/nidogen complexes, and proteoglycans. Collagen IV provides a scaffold for the other structural macromolecules by forming a network via interactions between specialized N- and C-terminal domains. Laminin entactin/nidogen complexes self-associate into less-ordered aggregates. These two molecular assemblies appear to be interconnected, presumably via binding sites on the entactin/nidogen molecule. In addition, proteoglycans are anchored into the membrane by an unknown mechanism, providing clusters of negatively charged groups. Specialization of different basement membranes is achieved through the presence of tissue-specific isoforms of laminin and collagen IV and of particular proteoglycan populations, by differences in assembly between different membranes, and by the presence of accessory proteins in some specialized basement membranes. Many cellular responses to basement membrane proteins are mediated by members of the integrin class of transmembrane receptors. On the intracellular side some of these signals are transmitted to the cytoskeleton, and result in an influence on cellular behavior with respect to adhesion, shape, migration, proliferation, and differentiation. Phosphorylation of integrins plays a role in modulating their activity, and they may therefore be a part of a more complex signaling system. PMID- 1309320 TI - Differential adrenergic regulation of beta 1- and beta 3-adrenoreceptor messenger ribonucleic acids in adipose tissues. AB - The levels of beta 1- and beta 3-adrenoreceptor mRNAs in several rat tissues were determined simultaneously with a sensitive nuclease protection assay. The beta 1 receptor gene was expressed to varying degrees in most tissues examined. By contrast, high levels of beta 3-receptor mRNA were only found in brown and white adipose tissues, indicating that beta 3-receptor gene expression is essentially adipose tissue specific. Surgical sympathectomy of interscapular brown adipose tissue increased beta 3-receptor mRNA levels by 2.4-fold, but did not affect beta 1-receptor mRNA levels. Exposure of rats to 4 C, which increases sympathetic nerve stimulation of IBAT, reduced beta 3-receptor mRNA levels in intact tissue but did not affect the denervation-induced increase in beta 3-receptor mRNA. Acute treatment of rats with norepinephrine greatly reduced beta 3 mRNA levels in both white and brown adipose tissues, but did not alter beta 1-receptor mRNA levels. These results indicate that beta 1- and beta 3-receptor mRNAs are differentially regulated and that norepinephrine released from sympathetic nerves is an important inhibitory regulator of beta 3-receptor mRNA levels. Injections of the beta-receptor agonist isoproterenol and the beta 3-receptor agonist BRL 26830 each reduced beta 3-receptor mRNA in brown and white fat, whereas injections of glucagon reduced beta 3-receptor mRNA in brown fat only. These data indicate that while stimulation of beta 3-receptors is sufficient to down regulate beta 3 mRNA, other receptors that stimulate adenylyl cyclase have the same effect. Finally, the agonist-induced down-regulation of beta 3-receptor mRNA was associated with a reduction in beta 3-receptor activation of adenylyl cyclase in white adipose tissue. PMID- 1309322 TI - Alpha-melanocyte-stimulating hormone is a mammotrophic factor released by neurointermediate lobe cells after estrogen treatment. AB - When neurointermediate lobe (NIL) cells from ovariectomized rats are exposed to 17 beta-estradiol (E2) in vitro, they release a substance that rapidly induces the recruitment of additional PRL cells into the secretory pool. In the present study we tested the hypothesis that this mammotrophic factor is alpha MSH. Cocultures of anterior pituitary and NIL cells were incubated for 18 h, exposed to various treatments for 3 h, and then subjected to a reverse hemolytic plaque assay to quantify the percentage of all pituitary cells that released PRL. Combined exposure to E2 and NIL cells caused a significant increase in the fraction of anterior pituitary cells that released PRL, and the presence of TRH during the reverse hemolytic plaque assay did not affect the magnitude of the response. Treatment with dopamine (which inhibits alpha MSH release) reversed the recruitment of PRL secretors induced by E2 stimulation of NIL cells. Likewise, immunoneutralization with an antiserum directed against alpha MSH abolished the response. Furthermore, alpha MSH alone could substitute for E2 and NIL cells in evoking the recruitment response, whereas none of several other POMC-derived peptides had any consistent effect. Taken together, these results demonstrate that alpha MSH is a mammotrophic factor released by NIL cells in response to E2. PMID- 1309321 TI - Suckling is a persistent stimulus to the adrenocortical system of the rat. AB - The present experiments investigated the hypothesis that lactation constitutes a chronic stress to the adrenocortical system. To determine whether the normal circadian control of the adrenocortical system or the ability to mount an adequate ACTH response to stress are modified during lactation, we compared morning and evening basal and stress-induced ACTH, corticosterone (B), and PRL secretion as well as pituitary ACTH content and thymus weight in virgins and lactating females on day 10 of lactation. We also compared the capacity of B to suppress ACTH secretion in adrenalectomized virgin or lactating females, both given various B pellet replacement doses (40-130% B) for 5 days. In addition, we investigated the influence of decreased litter size and increased caloric intake on basal circadian activity in the adrenocortical system. Finally, we measured suckling-induced activation of ACTH and B release and restoration of basal morning ACTH and B levels after pup separation. In all 10-d lactating females, basal PRL levels were elevated compared to virgins and the circadian rhythm observed in virgins (P less than 0.05) was absent in all lactating females. By contrast, diurnal variations in ACTH and B secretion (P less than 0.05 or 0.01) were observed in all females regardless of lactation and changes in caloric intake or litter size. Plasma ACTH and B were elevated during the trough of the diurnal rhythm in mothers, compared to virgins. The amplitude of the increase in ACTH between trough and peak was greater in mothers than virgins; however, the amplitude of the increase in plasma B was greater for virgins than mothers, probably because of the higher levels of corticosteroid binding globulin in the former. Diurnal rhythms in stress responsiveness and sensitivity of ACTH to B feedback were normal in mothers; however, the magnitude of their ACTH, B, and PRL response to ether stress was less in mothers than virgins. Attempts to normalize basal ACTH and B concentrations by increasing calorie consumption were unsuccessful. However, we found that suckling caused marked stimulation of ACTH and B secretion; moreover, within 24 h after pups removal, trough ACTH and B concentrations were restored to normal values.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309323 TI - Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation. AB - Cultured cardiac myocytes from adult Sprague-Dawley rats express both insulin like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man6P) receptors and respond to IGF-I with a dose-dependent accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4 bisphosphate [Ins(1,4)P2]. Specific binding of [125I]IGF-I to isolated membranes from cultured cardiac myocytes amounted to 1-1.2%. Binding of [125I]IGF-I was inhibited by unlabeled IGF-I at nanomolar concentrations and insulin at much higher concentrations. These data suggest that IGF-I binds to its own receptor on rat cardiac myocytes. Competitive binding studies using isolated membranes from cardiac myocytes and [125I]IGF-II showed 2-4% specific binding. Binding of [125I]IGF-II was inhibited by IGF-II and much less potently by IGF-I and insulin. Immunoglobulin G (IgG) 3637 (an IgG directed against the IGF-II/Man6P receptor) partially inhibited binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity cross-linking studies with [125I]IGF-II and cardiac myocyte membranes and subsequent analysis of the ligand-receptor complex using SDS-PAGE and autoradiography showed a radiolabeled band of approximately 250 kilodalton (kDa). The formation of the [125I]IGF-II-receptor complex was inhibited by incubation with IGF-II and IgG 3637 but not by insulin or nonimmune IgG. Western blotting of protein extracts from cultured cardiac myocytes was performed using IgG 3637 and an immunoperoxidase technique for the visualization of the IGF-II/Man6P receptor protein. A specific band at 220 kDa under nonreducing conditions was detected on the blots, providing further evidence for the expression of the IGF-II/Man6P receptor by cardiac myocytes. The effect of IGFs on the accumulation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo [3H]inositol-labeled cultured cardiac myocytes. IGF-I (50 ng/ml) stimulated the accumulation both of Ins(1,4,5)P3 and Ins(1,4)P2 after 30 sec by 43% and 63%. IGF II (up to 500 ng/ml) had no significant effect on inositol phosphate accumulation under the same conditions. However, in the presence of millimolar concentrations of Man6P, IGF-II (500 ng/ml) also increased Ins(1,4,5)P3 accumulation by 59%. We conclude that cardiac myocytes from adult rats express IGF receptors and respond to IGFs with the accumulation of Ins(1,4,5)P3 and Ins(1,4)P2. This effect seems to be mediated by an IGF-I receptor-specific pathway. PMID- 1309324 TI - Interleukin 1 beta mediates stress-induced immunosuppression via corticotropin releasing factor. AB - Intracerebroventricular (icv) infusion of human interleukin 1 beta (IL-1) into intact and adrenalectomized rats impairs immune function. Using antibody to IL-1 as well as an inhibitor of IL-1 action, we sought to determine if endogenous IL-1 in the central nervous system has a physiological role in mediating the immunosuppressive effects of stress. Compared with freely moving controls, rats given intermittent electric shock to the tail for 40 min exhibited a fall in T lymphocyte proliferation and natural killer (NK) cell cytotoxicity of 33% and 38%, respectively; however, when pretreated with icv human IL-1 monoclonal antibody, which significantly crossreacts with rat IL-1, the decrement was attenuated to 14.6% and 15%, respectively. When rats were pretreated with icv alpha-MSH, which blocks many IL-1 effects, shock-induced suppression of 42% in both T lymphocyte proliferation and NK cytotoxicity were blunted to 33% and 31%, respectively. Similar results were found in adrenalectomized rats. These findings suggest that endogenous IL-1 is a physiologically relevant mediator of the immune response to stress. As IL-1 has been reported to release CRF, which we have shown always plays a significant role in stress-induced immunomodulation, we then assessed the relationship of IL-1 and CRF in immunosuppression. Infusion of icv IL-1 caused a decrease of 35% in T lymphocyte proliferation and 34% in NK activity, but pretreatment with CRF antibody icv attenuated IL-1 suppression of T lymphocyte proliferation and NK activity to 10% and 8%, respectively. Comparable results were observed in adrenalectomized rats. These findings suggest that CRF antibody is able to block the immunosuppressive effects of IL-1. To further examine the interaction of CRF in mediating stress-induced immunosuppression, we found that animals pretreated with icv CRF antibody, shocked and then given icv IL-1, had a decrement in T lymphocyte proliferation and NK cytotoxicity of 24% and 21%, respectively, demonstrating that the immunosuppressive effect of icv IL 1 is blocked when central CRF has been neutralized by prior administration of icv CRF antibody. In contrast, animals pretreated with icv IL-1 antibody, shocked and then given icv CRF, had decrements of 38% and 40%, respectively, showing that icv CRF does act even when central IL-1 has been neutralized by prior administration of icv IL-1 antibody. Thus, we conclude there is a sequential relationship between two of the known mediators of stress-induced immunosuppression, with release of central IL-1 followed by that of CRF. PMID- 1309325 TI - Insulinotropic hormone glucagon-like peptide-I(7-37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. AB - Glucagon-like peptide-I(7-37) [GLP-I(7-37)] is an intestinal peptide hormone that is released in response to oral nutrients and that potently augments glucose mediated insulin secretion. GLP-I(7-37) has potent insulin-releasing activities in vivo in response to oral nutrients, in situ in the isolated perfused pancreas, and in vitro in cultured pancreatic B-cells. As such GLP-I(7-37) is a potent hormonal mediator in the enteroinsular axis involved in the regulation of glucose homeostasis. We now show that in addition to stimulating the release of insulin, GLP-I(7-37) stimulates proinsulin gene expression at the levels of gene transcription and cellular levels of proinsulin messenger RNA as well as the translational biosynthesis of proinsulin. These findings of the positive anabolic actions of GLP-I(7-37) on the synthesis of insulin in B-cells support the notion that GLP-I(7-37) may be of therapeutic use in stimulating the production of insulin in patients with noninsulin-dependent diabetes mellitus and that overproduction of insulin with subsequent hypoglycemia will not occur in response to the administration of GLP-I(7-37). Furthermore, these positive actions of GLP I(7-37) on insulin production obviate the possibility of B-cell exhaustion in response to such a potent secretagogue. PMID- 1309326 TI - pH dependence of inhibition of arginine vasopressin-induced adenosine 3',5' monophosphate production by cellular sodium depletion in rat renal inner medullary collecting duct cells in culture. AB - The present study was undertaken to determine whether the change in cellular Na+ concentration ( [Na+]i) or cellular pH (pHi) is essential for the modulation by Na+/H+ antiporter of the cellular action of arginine vasopressin (AVP) in renal inner medullary collecting duct cells in culture. Extracellular Na+ depletion promptly decreased [Na+]i from 15.8 to 5.4 mM (P less than 0.01), which was closely related to the decrease in pHi (7.19 to 6.97; P less than 0.01). In the presence of 0.5 mM 3-isobutyl-1-methylxanthine, AVP increased cellular cAMP production in a dose-dependent manner. This was significantly blunted in the Na(+)-depleted cells (1 nM AVP; 481.9 vs. 341.0 fmol/micrograms protein; P less than 0.01). When cells were incubated with the Na(+)-depleted medium containing 25 mM NaHCO3, [Na+]i decreased promptly, but the pHi remained unchanged. Under this condition, the AVP-induced increase in cellular cAMP production was not altered (1 nM AVP; 390.9 vs. 334.8 fmol/micrograms protein). Also, after the Na(+)-depleted cells were incubated in 20 mM NH4Cl, which promptly normalized pHi despite the decreased [Na+]i, the response of cAMP production to AVP was restored. Amiloride (1 x 10(-5)-1 x 10(-3) M), which blocks the Na+/H+ exchange, decreased pHi and AVP- and forskolin-induced cAMP production in a dose-dependent manner. These results indicate that the decrease in [Na+]i promptly inhibits AVP induced cAMP production mediated through the reduction in pHi in renal inner medullary collecting duct cells. PMID- 1309327 TI - Relaxin receptors in mice: demonstration of ligand binding in symphyseal tissues and uterine membrane fragments. AB - A monocomponent, high specific activity, carrier-free porcine relaxin tracer (125I) has made it possible for us to demonstrate relaxin receptors in the symphysis pubis, uterus, and ovary via autoradiography. The receptors are concentrated in the symphyseal ligament and the peripheral layers of uterus and ovary. Specific relaxin binding was observed in crude membrane preparations of uteri, ovaries, and brain, whereas crude membranes of leg muscle and kidney showed only nonspecific binding. Uterine membranes prepared from estrogen-primed mice showed tracer binding, which could be significantly inhibited by porcine relaxin in a dose-dependent manner, but not by insulin. A linear Scatchard plot suggested the presence of only one kind of receptor and a dissociation constant of 5 x 10(-10) M, which is commensurate with an electrostatic double ion pair binding mechanism. PMID- 1309328 TI - Epidermal growth factor inhibits follicular response to human chorionic gonadotropin: possible role of cell to cell communication in the response to gonadotropin. AB - Epidermal growth factor (EGF) affects follicular steroidogenesis and expression of gonadotropin receptors. The effects of EGF on hCG-induced estradiol and progesterone secretion and ovulation were examined in the in vitro perfused rabbit ovary. We also examined the effects of EGF on hCG-induced progesterone secretion by isolated granulosa cells. In addition, distribution of hCG within the follicle was probed by immunohistochemical means 30 min after its administration to the in vitro perfused ovary. EGF significantly (P less than 0.05) reduced hCG-induced secretion of estradiol (control, 117 +/- 12 pg/min.follicle; 10 ng/ml EGF, 55 +/- 10) and progesterone (control, 18.2 +/- 1.2 ng/min.follicle; 10 ng/ml EGF, 11.9 +/- 0.8) by the perfused ovary. In contrast, EGF did not inhibit hCG-induced progesterone secretion by isolated granulosa cells. Ovulatory efficiency (number of ovulated ova per number of mature follicles x 100) when EGF was given 30 min before hCG was reduced dose dependently from 58.2% with no EGF to 8.3% with 10 ng/ml EGF (P less than 0.001). Ovulation was not inhibited by EGF when it was given 30 min after hCG. Distribution of hCG in the preovulatory follicle was confined to the basement membrane, thecal cell layer, and a small fraction of the outer granulosa cell layer. These observations suggest that gonadotropin stimulates the follicle through the release of a secondary signal(s) from ligand-bound granulosa cells near the follicle wall to unexposed cells of the inner avascular area. EGF may inhibit the follicular response to hCG by attenuation of this cell to cell communication. PMID- 1309329 TI - Verapamil corrects abnormal metabolism of pancreatic islets and insulin secretion in phosphate depletion. AB - Phosphate depletion (PD) causes impaired insulin secretion and metabolic derangements in pancreatic islets. We studied PD, pair-weighed (PW), and PD and PW rats treated with verapamil (PD-V and PW-V) to examine the mechanisms of these derangements. Cytosolic calcium ([Ca2+]i) in PD islets was higher than that in PW, PD-V, and PW-V islets, and the values in the latter three groups were not different. Both basal and stimulated ATP in PD islets were lower than those in PW, PW-V, or PD-V islets. The maximum velocity (Vmax) of Ca(2+)-ATPase and the Km and Vmax of Na+,K(+)-ATPase were reduced in PD islets. In both PD-V and PW-V, the Vmax of Ca(2+)-ATPase was higher than that in PD, but lower than that in PW. Both initial and second phases of insulin secretion by PD islets were lower than those by PW and PW-V islets. In PD-V rats, insulin secretion was greater than that in PD rats, but only the second phase was significantly higher. The data are consistent with either of the following possibilities: 1) PD causes a change in the permeability of islets, allowing increased entry of Ca2+ into them and a fall in ATP of islets; the latter would impair the activity of both ATPases, leading to reduced Ca2+ extrusion from islets and, hence, an elevation in their [Ca2+]i; or 2) the primary defect in PD is a reduction in the activities of ATPases of islets due to the fall in ATP secondary to phosphorus deficiency. The decreased Ca2+ extrusion that ensues, even in the face of normal Ca2+ entry, will result in high [Ca2+]i. In either of these scenarios the rise in [Ca2+]i would inhibit mitochondrial oxygen consumption and ATP production, further lowering the ATP content of the islets. The higher [Ca2+]i and low ATP of PD underlie the impaired insulin secretion. Verapamil, by blocking normal or augmented Ca2+ entry into the islets, mitigates or prevents the derangements in islet function and metabolism. PMID- 1309330 TI - Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. AB - To elucidate the ligand-receptor relationship of the natriuretic peptide system, which comprises at least three endogenous ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), and three receptors, the ANP-A receptor or guanylate cyclase-A (GC-A), the ANP-B receptor or guanylate cyclase-B (GC-B), and the clearance receptor (C-receptor), we characterized the receptor preparations from human, bovine, and rat tissues and cultured cells with the aid of the binding assay, Northern blot technique, and the cGMP production method. Using these receptor preparations, we examined the binding affinities of ANP, BNP, and CNP for the C-receptor and their potencies for cGMP production via the ANP-A receptor (GC-A) and the ANP-B receptor (GC-B). These analyses revealed the presence of a marked species difference in the receptor selectivity of the natriuretic peptide family, especially among BNPs. Therefore, we investigated the receptor selectivity of the natriuretic peptide family using the homologous assay system with endogenous ligands and receptors of the same species. The rank order of binding affinity for the C-receptor was ANP greater than CNP greater than BNP in both humans and rats. The rank order of potency for cGMP production via the ANP-A receptor (GC-A) was ANP greater than or equal to BNP much greater than CNP, but that via the ANP-B receptor (GC-B) was CNP greater than ANP greater than or equal to BNP. These findings on the receptor selectivity of the natriuretic peptide family provide a new insight into the understanding of the physiological and clinical implications of the natriuretic peptide system. PMID- 1309331 TI - Altered expression of insulin-like growth factor-I (IGF-I) and IGF receptor genes after unilateral nephrectomy in immature rats. AB - There is a developmental difference in the initial phase of compensatory renal growth (CRG) following unilateral nephrectomy (UNX), in that CRG is GH-dependent in adult rats and GH-independent in immature rats. Furthermore, CRG in immature rats is associated with an increase in renal IGF-I mRNA, an effect not seen in adult rats. In this study we have examined the age-related differences in expression of the insulin-like growth factor-I (IGF-I) and IGF-II genes as well as in IGF-I and IGF-II receptors and membrane binding after UNX. Immature (22-24 days of age) and adult (4 months of age) male Wistar rats underwent a sham operation or left UNX and were killed 24 or 48 h later. Levels of mRNA for IGF-I and IGF-II and their receptors were determined in the left (control) and right (compensated) remnant kidneys using solution hybridization/RNase protection assays. Steady state levels of IGF-I mRNA as well as IGF-I receptor and IGF II/mannose-6-phosphate receptor mRNAs were increased 3- to 4-fold in immature remnant kidneys, but not in adult kidneys. The findings related to IGF-I gene expression were confirmed by in situ hybridization to immature and adult kidney slices. The increase in IGF-I gene expression in the immature remnant kidneys was localized to the thick ascending limbs of the loops of Henle. Furthermore, in concert with the changes in mRNA levels, membrane binding studies showed significant increases in specific binding to IGF-I in cortical membranes and increases in specific binding to IGF-II in whole kidney membranes from immature, but not adult, rats. Thus, these findings demonstrate that the initial phase of CRG in the immature rat is associated with increased renal IGF-I gene expression as well as enhanced specific renal binding of IGF-I and IGF-II to plasma membranes and support the notion that this period of rapid renal growth in the immature UNX rat may involve the paracrine influence of the IGFs. PMID- 1309332 TI - Binding and metabolism of 1,25-dihydroxyvitamin D3 in cultured bovine parathyroid cells. AB - Several laboratories, including ours, have reported that receptors for 1,25 dihydroxyvitamin D3 [1,25-(OH)2D3] are decreased in parathyroid glands of uremic animals and patients. To elucidate the factors involved in receptor regulation in this tissue, we have characterized the receptor in primary cultures of bovine parathyroid cells. Extracts from these cells contain a single binding component that binds 1,25-(OH)2D3 with a Kd of 58 pM and sediments in sucrose density gradients at 3.4S, indicating the continued expression of the vitamin D receptor in these cells. Labeling of the intact parathyroid cells with tritiated 1,25 (OH)2D3 was maximal by 2 h, and binding affinity by this method was estimated to be 22 pM. Longer incubation of the cells with tritiated 1,25-(OH)2D3 resulted in a loss of specific binding to 10% maximal by 12 h. The decrease in binding correlated temporally with degradation of 1,25-(OH)2D3 in the medium. This metabolic activity was absent in vitamin D-deficient cells and was first detectable 3-4 h after the addition of 1,25-(OH)2D3, indicating that 1,25-(OH)2D3 induces its own metabolism in parathyroid cells. Replenishment of the cultures after 12 h with fresh tritiated 1,25-(OH)2D3 restored maximal binding, demonstrating that the loss of binding was not due to down-regulation of receptor. Inclusion of the cytochrome P450 inhibitor ketoconazole did not alter maximal binding at 2 h, but blocked both the metabolism of 1,25-(OH)2D3 and the decrease in binding after 3 h. In contrast to other cell types, such as osteosarcoma cells, no homologous up-regulation was seen in cultured parathyroid cells even after 12 h in the presence of 0.5 nM 1,25-(OH)2D3. Furthermore, receptor levels in preparations from cells treated for 20 h with unlabeled 1,25 (OH)2D3 at concentrations of 0.1, 1.0, and 10 nM were not different from controls. Thus, it appears that the vitamin D receptors in parathyroid cell cultures are not up-regulated by their ligand. PMID- 1309333 TI - Physiological role of corticotropin-releasing factor in the control of adrenocorticotropin-mediated corticosterone release from the rat adrenal gland. AB - Marked fluctuations in adrenal sensitivity to ACTH have been reported under both physiological (e.g. diurnal) and experimental conditions. Recently, we reported that immunoneutralization of CRF reduces resting corticosterone (cort) levels in rats without inducing concomitant reductions in plasma ACTH. We postulated an endogenous CRF mechanism that controls the adrenal sensitivity to ACTH. In the present study, this hypothesis was tested by iv infusion of human ACTH (0, 1, 3, and 10 ng/kg.min for 60 min) into dexamethasone-treated anaesthetized male Wistar rats. Serial blood samples were taken for the determination of ACTH and corticosterone by RIA (ACTHi, corti). Infusion of ACTH resulted in dose-dependent steady state plasma ACTHi levels, ranging from 50-600 pg/ml, which were not affected by prior administration of a rat monoclonal antibody to rat CRF (PFU 83). As expected, infusion of ACTH resulted in a dose-dependent increase in plasma corti. In PFU 83-treated rats, preinfusion plasma corti levels were reduced compared to those of rat immunoglobulin G-treated controls (7.8 +/- 1.2 vs 25.3 +/- 3.2 ng/ml). In addition, the corti responses to infusion of 1 and 3 ng/kg.min ACTH were suppressed by PFU 83. However, at a (near) maximally effective dose of ACTH (10 ng/kg.min), no differences in plasma corti were found between PFU 83 and immunoglobulin G-treated rats. These findings suggest that immunoneutralization of endogenous CRF results in a 3-fold reduction of the adrenal sensitivity to ACTH. Subsequently, we studied the possible effects of exogenous CRF on the isolated perfused adrenal gland in situ. In this preparation, CRF alone (1-100 pmol) or ACTH alone (5 fmol) did not affect the corti secretion rate or the flow rate of the perfusion medium through the gland. However, when given together a marked (up to 3.2 times) CRF dose-dependent stimulation of corti secretion and an increase (up to 1.7 times) in adrenal flow rate were obtained. In experiments with freshly dispersed adrenal cells in vitro, PFU 83 (1 microM) or CRF (0.1-10 nM) did not influence corti secretion when given alone and did not affect ACTH-induced corti secretion. It is unlikely, therefore, that CRF acts directly on the steroid-producing cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309334 TI - Parathyroid hormone-related protein binding to human T-cell lymphotropic virus type I-infected lymphocytes. AB - An HTLV-I-infected human lymphocyte line (MT-2) was evaluated for 1) the presence of receptors for PTH-related protein (PTHrP), 2) cell proliferation in response to PTHrP, and 3) adrenylate cyclase and intracellular calcium response to PTHrP. PTHrP-(1-36) was labeled with 125I, purified, and used to detect binding to MT-2 cells. Specific binding ranged between 4-9% of the total radioactivity. Specific binding increased with increasing cell number, was maximal within 30-60 min, and was highest at 37 C. Scatchard analysis revealed a one-binding site fit, with a Kd of 14.5 nM. Binding was not competed for by calcitonin, calcitonin gene related peptide, or interleukin-1 beta. PTHrP at 1.0 and 0.1 microM inhibited proliferation in MT-2 cells. PTHrP did not alter adenylate cyclase stimulation in MT-2 cells, but did cause an increase in intracellular calcium. These findings indicate that MT-2 cells have receptors for PTHrP and are consistent with a potential autocrine role of PTHrP in HTLV-I-infected lymphoid cells. PMID- 1309335 TI - Drop in the "atypical" beta-adrenergic response and modification of the beta/alpha 2-adrenoceptor balance in fat cells from aging rabbits. AB - Previous studies have shown a strong reduction of catecholamine-induced lipolysis in perirenal white fat cells in aging rabbits. The molecular basis of this observation was explored on scapular and perirenal adipocytes from 45 and 300- to 500-day-old rabbits. ACTH and forskolin were used to define the maximal lipolytic potencies of the adipocytes. beta-Adrenergic responsiveness was explored with isoproterenol and specific agonists of the "atypical" beta-adrenoceptor (beta-AR) (BRL37344 and (+/-)CGP12177); beta 1/beta 2-ARs were identified with [125I]cyanopindolol. alpha 2-adrenergic responses were evaluated with the full alpha 2-agonist, UK14304. The alpha 2 AR number was determined with the alpha 2 antagonist radioligand [3H]RX821002. Whatever the fat deposit, the relative order of lipolytic potency of the beta-agonists was: isoproterenol greater than BRL37344 greater than (+/-)CGP12177. As previously reported for catecholamines, the maximal lipolytic response initiated by isoproternol decreased with aging; the stronger reduction was observed in perirenal adipocytes compared to subscapular adipocytes. The most striking observation concerns the parallel and complete disappearance of the lipolytic responses induced by the atypical beta agonists (BRL37344 and (+/-)CGP12177) and the preservation of a residual action of isoproterenol (30% of that described in young animals) which was attributed to the stimulation of beta 1/beta 2-ARs. The number of beta 1/beta 2-AR binding sites was practically equivalent whatever the fat deposite and the age of the animals. alpha 2-Adrenergic responsiveness and alpha 2-adrenergic receptor number were increased with aging in the various deposits but the stronger changes were observed in the perirenal adipocytes where epineprine initiated a biphasic effect on lipolysis (antilipolytic and then lipolytic). To conclude, the reduction of catecholamine-induced lipolysis observed in the rabbit fat cells with aging can be explained by changes in the atypical beta-AR/alpha 2-AR balance. First, a loss of responsiveness to the atypical beta-adrenergic agents was observed (it is impossible for the moment to distinguish between the loss of atypical beta-AR binding sites and their putative uncoupling from the adenylate cyclase system) whereas beta 1/beta 2-AR-mediated responses were maintained. Second, an increment of alpha 2-adrenergic responsiveness and of the alpha 2-AR binding sites accompanied aging and fattening. In the absence of, or after a strong reduction of the atypical beta-AR component of the lipolytic response in fat cells of aged rabbits, epinephrine exerts a biphasic effect on lipolysis, demonstrating the changes occurring in the atypical beta-AR/alpha 2-AR balance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309336 TI - Androgenic regulation of adipocyte alpha 2-adrenoceptor expression in male and female Syrian hamsters: proposed transcriptional mechanism. AB - Adaptation of male hamsters to short daily (SD) photoperiod induced a reduction of the adipocyte alpha 2-adrenoceptor (alpha 2-AR) expression which was related to a sexual involution and could be reversed by testosterone administration. In the present paper, the possible mechanisms of such a physiological regulation are explored. The effect of testosterone on the adipocyte alpha 2-AR was rapid, dose dependent, occurred at the physiological plasma concentrations of androgen, and was mimicked by dihydrotestosterone, but not by 17 beta-estradiol, progesterone, hydrocortisol, insulin, or T3. Adaptation of female hamsters to SD photoperiod also induced a sexual involution, but no modification of the adipocyte alpha 2-AR number was observed. Administration of testosterone induced a large up-regulation of the adipocyte alpha 2-AR. Testosterone was also able to up-regulate the adipocyte alpha 2-AR in male hamsters adapted to long day photoperiod whatever their age (6-, 12-, and 25-week old). Adaptation to SD photoperiod did not modify the adipocyte adenylyl cyclase activity (basal, forskolin-stimulated, GppNHp inhibited). Conversely, UK14304-mediated inhibition of the adenylyl cyclase was suppressed in SD photoperiod and recovered after testosterone treatment. Administration of testosterone in young male hamsters adapted to long day photoperiod induced an increase in the amount of the alpha 2-AR messenger RNA, which coincided with the increase in the alpha 2-AR maximal number. The existence of a specific regulation of the adipocyte alpha 2-AR by the androgens, probably via a transcriptional mechanism, can be hypothesized. This regulation, which occurs in both male and female hamsters, appears to be physiologically relevant. PMID- 1309337 TI - Altered proximal tubule glucose metabolism in X-linked hypophosphatemic mice. AB - In the present study we examined renal proximal tubule glucose metabolism in the X-linked hypophosphatemic (Hyp/Y) mouse. Compared to those in its normal (+/Y) littermate, Hyp/Y mouse proximal tubules showed a higher rate of glucose production when using glutamine or alpha-ketoglutarate as a substrate. The glucose production rate was not, however, different when using malate or fructose as the substrate. PTH stimulated glucose production in +/Y, but not Hyp/Y, mouse proximal tubules. The PTH resistance in Hyp/Y mouse involves steps at and post cAMP formation, because in Hyp/Y mouse proximal tubules PTH effects a lesser stimulation of cAMP generation, and addition of 8-bromo-cAMP failed to increase the glucose production rate. The rate of glucose utilization as a whole was not different in the two groups, but the rate of glucose metabolized through the pentose cycle (PC) pathway was markedly lower in Hyp/Y mouse proximal tubules. The lower PC activity in Hyp/Y mouse proximal tubules did not result from a defect of PC enzymes, because both glucose-6-phosphate dehydrogenase and 6 phosphogluconate dehydrogenase enzyme activities were intact, and phenazine methosulfate was able to stimulate PC activity. The higher rate of glucose production and the lower rate of PC activities persisted in the in vitro cultured Hyp/Y mouse proximal tubular cells. These results suggest that the altered glucose metabolism in the Hyp/Y mouse proximal tubule is not maintained by external influences and may be an abnormality intrinsic to these cells. PMID- 1309338 TI - Effects of calcitonin on 3',5'-cyclic adenosine monophosphate and calcium second messenger generation and osteoblast function in UMR 106-06 osteoblast-like cells. AB - The UMR 106-06 rat osteosarcoma osteoblast-like cell line possesses calcitonin (CT) receptors in addition to expressing PTH receptors and a highly osteoblast like phenotype, and may represent an intermediate developmental stage between early osteoblast precursors and mature osteoblasts. Therefore, we examined the effects of CT and PTH on second messenger generation and osteoblastic function in these cells. In UMR-106-06 cells, 10-1000 nM CT produced a dose-dependent stimulation of intracellular free calcium concentration ([Ca2+]i), which reached a plateau between 2-3 min. This stimulatory effect was abolished in the absence of extracellular Ca2+ ([Ca2+]o) and was mimicked by forskolin and (Bu)2cAMP. One hundred nanomolar CT also produced a slight but significant increase in inositol triphosphate production (13%, P less than 0.05) but did not produce a rapid, transient increase in [Ca2+]i. In contrast, PTH produced a rapid, transient increase in [Ca2+]i, which reached a maximum within 30 sec. This stimulatory effect of PTH on [Ca2+]i signal was dose-dependent and accompanied by a parallel stimulation of inositol triphosphate production. PTH, forskolin, and (Bu)2cAMP all produced a marked dose-related suppression of both DNA and collagen synthesis, which paralleled their stimulatory effects on intracellular cAMP levels. In marked contrast, CT only minimally reduced DNA and collagen synthesis despite producing comparable increases in intracellular cAMP. One hundred nanomolar CT also stimulated alkaline phosphatase specific activity by 33% (P less than 0.05). Thus, CT stimulates cAMP, [Ca2+]i, and inositol phosphate second messengers in UMR 106-06 cells. However, in contrast to other agents which elevate intracellular cAMP levels, CT does not suppress DNA synthesis. These results suggest that the linkage of CT receptor second messengers to effects on cell function differ from those of PTH and/or that CT may produce additional second messenger(s) which antagonize the antiproliferative effect of increased cAMP levels in UMR-106-06 cells. PMID- 1309339 TI - Participation of the Na+/H+ exchanger in the phospholipase-A2 activation of luteinizing hormone-releasing hormone release in rat hypothalamic fragments. AB - The role of the Na+/H+ exchanger in the phospholipase-A2 (PLA2) stimulation of LHRH release was investigated using in vitro incubations of rat hypothalamic fragments. It was found that monensin, the Na+/H+ ionophore, increased LHRH release in a dose-related manner. That effect diminished in the absence of calcium as well as after the addition of 2,4'-dibromoacetophenone, a blocker of PLA2 action. Amiloride, a blocker of the Na+/H+ exchanger, did not alter the effect of monensin. However, amiloride significantly diminished the effect of melittin, an activator of PLA2 action. LHRH release under PLA2 did not change when amiloride was added to the incubation medium. Lysophosphatidylcholine also increased LHRH release. These results were interpreted as evidence of the participation of Na+/H+ exchange in PLA2 activation in the release of LHRH in rat hypothalamic fragments. A role of lysophospholipids in this process is also suggested. PMID- 1309340 TI - Hydrogen peroxide generation and its regulation in FRTL-5 and porcine thyroid cells. AB - Hydrogen peroxide acts as electron acceptor in the oxidative reactions (iodination and coupling) by which the thyroid hormones are formed. Regulation of the generation of H2O2 was studied in monolayer cultures of the FRTL-5 rat thyroid cell line and in primary monolayer cultures of porcine thyroid cells. Both cell types were grown in a medium containing either a six-hormone mixture, including TSH (6H), or a five-hormone mixture without TSH (5H) for 1 to several days before the experiment. The production of H2O2 was measured with the homovanillic acid fluorescence assay and expressed as picomoles of H2O2 formed per min/microgram DNA. In FRTL-5 cells grown in 6H medium, only a weak and varying stimulation of H2O2 production was induced by TSH at high concentration (greater than 10 mU/ml), and no stimulation was seen by TSH at low concentration or by 8-bromo-cAMP, whereas forskolin had a good stimulatory effect. In FRTL-5 cells grown in 5H medium for 1-3 days, all three substances were potent stimulators. In porcine thyrocytes examined in the same way, none of the three presumptive stimulators had any effect in 6H cultures, and only TSH (at high concentration) had a weak effect in 5H medium. ATP, a stimulator of the Ca2+/phosphatidylinositol cascade via a P2-purinergic receptor, had no effect on H2O2 generation in FRTL-5 cells in 6H medium. Phorbol myristate acetate (PMA), a direct activator of protein kinase-C, induced a weak stimulation in these cells. In FRTL-5 cells in 5H medium, both ATP and PMA evoked a strong, and similar, enhancement of H2O2 production. In porcine cells in 6H medium, ATP evoked a moderate and PMA a strong stimulation; the effects in 5H were similar to the corresponding effects in 6H medium. The observations are interpreted to show that in FRTL-5 cells the regulation of H2O2 generation uses both the cAMP cascade and the Ca2+/phosphatidylinositol cascade, whereas in porcine thyrocytes the cAMP route is unimportant. In FRTL-5 cells the Ca2+/phosphatidylinositol cascade may be influenced by the cAMP system. PMID- 1309341 TI - Spironolactone, an aldosterone antagonist, acts as an antiglucocorticosteroid on the mouse mammary tumor virus promoter. AB - The ability of the glucocorticosteroid receptor to bind mineralocorticosteroids suggests that spironolactone, a potent aldosterone antagonist, may also interact with the glucocorticosteroid receptor, resulting in an agonist or antagonist glucocorticosteroid activity. We have investigated the effect of this drug on the activity of the glucocorticosteroid-regulated mouse mammary tumor virus (MMTV) promoter. For these studies we used the mouse fibroblast cell line 1471.1. It contains about 200 copies of a permanently established chimeric DNA construct comprising a transcription unit [MMTV long terminal repeat (LTR)] driving the reporter gene chloramphenicol acetyltransferase linked to the 69% transforming fragment of the bovine papilloma virus genome. This cell line has a high level of glucocorticosteroid receptor (1200 fmol/mg protein) and no detectable mineralocorticosteroid receptor. Competition experiments showed a binding of spironolactone to glucocorticosteroid receptor, with an affinity 50-fold lower than that of dexamethasone. In these cells, spironolactone behaves as an antiglucocorticosteroid, inhibiting in a dose-dependent fashion dexamethasone induced chloramphenicol acetyltransferase activity, with an ED50 of 8 microM. The absence of agonist activity, even at a high concentration of this compound (10 microM), demonstrates that spironolactone is a pure antiglucocorticosteroid in this cell line. MMTV LTR DNase-I hypersensitivity studies demonstrated that spironolactone, when administered in combination with dexamethasone, inhibits formation of the hormone-induced hypersensitive site located about 160 basepairs up-stream of the MMTV cap site. Furthermore, spironolactone alone failed to induce this DNase-I-hypersensitive site, suggesting that the antagonist-receptor complex does not interact productively with MMTV LTR chromatin. PMID- 1309342 TI - Stimulation of bone nodule formation in vitro by prostaglandins E1 and E2. AB - It has been established by organ culture experiments that prostaglandins (PGs) stimulate bone resorption in vitro. Experiments in vivo and with organ cultures suggest that PGs may also stimulate bone formation, and that bone formation in response to a variety of environmental stimuli is PG dependent. We have tested the ability of PGE1, PGE2, and PGF2 alpha to induce bone formation in cultures of rat calvarial cells. PGE1 and PGE2 significantly increased bone nodule formation at concentrations of 10(-8) M and above, to reach 3 times the control levels at 10(-7) M. PGF2 alpha was without effect. The increase in the number of nodules was effected without a significant change in the number of cells in control and test cultures with a logarithmic phase of growth, and there was no increase in the average size of the nodules. This suggests that PGs acted through induction of nodule formation by a population of cells that would not otherwise have produced nodules. Nodules were induced by PGs if the PGs were present in the early stages of the cultures; osteoblastic cells incubated with PGs for 8 days produced very similar numbers of nodules as cultures incubated with PGs throughout the 21-day culture period, although nodules did not become identifiable until 8-10 days of incubation. The addition of PGs late in the culture period had little effect on nodule formation. These experiments identify a role for PGs in bone formation in vitro, which may represent a pathway common to the bone anabolism that is observed in response to many environmental stimuli. PMID- 1309344 TI - Endothelin ETA receptors mediate the signaling and secretory actions of endothelins in pituitary gonadotrophs. AB - Specific receptors for endothelin (ET), localized by autoradiographic studies with [125I]ET in frozen sections of the rat pituitary gland, were abundant in the adenohypophysis, but not in the neurohypophysis. Specific binding of [125I]ET-1 and [125I]ET-3 was also demonstrable in 3-day-old primary cultures of anterior pituitary cells. The binding of [125I]ET-1 to its receptors was time and temperature dependent and was followed by rapid internalization of the receptor ligand complex. Binding of [125I]ET-1 and [125I]ET-3 to pituitary tissues and cells was more effectively displaced by ET-1 and ET-2 than by ET-3. In cultured pituitary cells, ET-1 caused a rapid increase in polyphosphoinositide hydrolysis, and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production, with a prompt rise in the cytoplasmic calcium concentration ([Ca2+]i) and LH secretion. The Ins(1,4,5)P3 response to 100 nM ET-1 was transient, with a spike at 10 sec followed by an exponential decrease toward the low steady state level. Ins(1,3,4)P3 and inositol bisphosphate (InsP2) increased more slowly, reaching peak values 30-40 sec after stimulation. The kinetics of the [Ca2+]i response to ET-1 were similar to those of the Ins(1,4,5)P3 response and more rapid than those of the Ins(1,3,4)P3 and InsP2 responses. In perifused cells, ET-stimulated increases in LH release showed the same biphasic patterns as the Ins(1,4,5)P3 and [Ca2+]i responses. ET-1 was more potent than ET-3 in stimulating [Ca2+]i and LH responses, consistent with its higher affinity for the pituitary ET receptors. The initial activation of Ca2+ signaling and LH exocytosis by ETs was followed by prolonged refractoriness to both ET-1 and ET-3. The development of desensitization occurred more rapidly in ET-1- than ET-3-stimulated cells and correlated temporally with endocytosis of the receptor-ligand complex. These findings indicate that stimulation of gonadotropin release by ETs occurs via activation of ETA-type receptors, which are coupled to polyphosphoinositide hydrolysis and [Ca2+]i mobilization, and undergo rapid internalization and profound desensitization. PMID- 1309343 TI - Identification and functional characterization of adenylate cyclase-linked receptors for parathyroid hormone-like peptides on immortalized human keratinocytes. AB - We have identified and characterized receptors for the amino-terminal domains of PTH and PTH-like peptide (PLP) on an immortalized human keratinocyte cell line, RHEK-1. Binding of both PLP-(1-34) and PTH-(1-34) to the RHEK-1 cells was consistent with a two-site model; affinities and capacities for each site were similar for the two peptides. Both peptides also stimulated adenylate cyclase activity with an equal ED50 in this cell line. Pertussis toxin pretreatment enhanced this peptide-mediated enzyme activity, suggesting linkage of the receptor to an inhibitory guanyl nucleotide-binding protein (Gi). Adenylate cyclase activity was diminished by both homologous [PLP-(1-34)] and heterologous [epidermal growth factor (EGF)] effectors. Malignant conversion of the immortalized cells with an activated H-ras oncogene to produce the RHEK-ras cell line was associated with a reduction in binding at both PLP/PTH and EGF receptors as well as a postreceptor defect in PLP/PTH-stimulated adenylate cyclase activity. The defect in enzyme activity appeared to be due in part to a decrease in the activity of the stimulatory guanyl nucleotide-binding protein (Gs), but not to an increase in Gi activity. Activation of the keratinocyte amino-terminal PLP/PTH receptor resulted in a small increase in [3H]thymidine incorporation, which was associated with an increase in cell numbers. This mitogenic effect was enhanced in the presence of EGF and was markedly reduced when cells were cultured in a high extracellular calcium environment. These studies demonstrate that the amino-terminal region of PLP and PTH activates adenylate cyclase-linked receptors, which are associated with mitogenesis, in RHEK-1 cells and suggest that this cell line represents a suitable model in which to examine the actions of PLP in keratinocytes. PMID- 1309345 TI - Pharmacological characterization of vasotocin stimulation of phosphoinositide turnover in frog adrenal gland. AB - In a previous report we demonstrated the presence of a vasotocin (AVT)-like peptide in chromaffin cells of the amphibian adrenal gland and showed that synthetic AVT is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells. In the present study we evaluated the relative potency of various AVT analogs and investigated the mechanism of action of AVT on frog interrenal (adrenal) tissue. Several AVT agonists, including hydrin 2, oxytocin (OXT), arginine vasopressin (AVP), Lys-conopressin G, and mesotocin (MT), were able to mimic the stimulatory effect of AVT on steroid secretion, but AVT was by far the most potent stimulator of steroidogenesis. In the series of analogs studied, the order of potency was: AVT greater than hydrin 2 greater than OXT greater than AVP greater than Lys-conopressin G greater than MT greater than [deamino-Cys1,D-Arg8]AVP greater than [d(CH2)5,Tyr(OMe)2] AVP. The effect of AVT (5 x 10(-10) M) was totally blocked by both the antidiuretic V2 antagonist [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP (10(-6) M) and the oxytocinergic antagonist [d(CH2)5,Tyr(OMe)2,Orn8]AVT (10(-6) M); the V2 antagonist was approximately twice as potent as the OXT antagonist. In contrast, the V1 antagonist 1-(1-mercapto-4 phenylcyclohexaneacetic acid)-AVP (10(-6) M) did not affect the response of the interrenal tissue to AVT. Indomethacin (5 microM), a cyclooxygenase inhibitor, induced a dramatic decrease in the spontaneous secretion of corticosteroids, but did not impair the stimulatory effect of AVT (5 x 10(-9) M) on corticosterone and aldosterone secretion. In addition, AVT did not stimulate the production of prostaglandin E2, suggesting that prostaglandins are not involved in the mechanism of action of AVT. Concurrently, AVT did not modify cAMP production by frog adrenal slices. In contrast, AVT induced both an increase in inositolphosphate production and a reduction of membrane phospholipid content. We conclude that in the frog adrenal gland, the stimulatory effect of AVT on steroid secretion is mediated through activation of receptors related to the mammalian V2 and/or OXT receptors, which are positively coupled to phosphoinositide-specific phospholipase C. PMID- 1309346 TI - Evidence for a modulation of human chorionic gonadotropin (hCG) subunit messenger ribonucleic acid levels and hCG secretion by gamma-aminobutyric acid in human first trimester placenta in vitro. AB - The cytotrophoblasts are the site of production of liberins and statins in human placenta, whereas the syncytiotrophoblasts synthesize tropic hormones. These placental cell layers seem to interact like the hypothalamus and pituitary. In the central nervous system, gamma-aminobutyric acid (GABA)-ergic neurons represent one important control mechanism that seems to influence the lutropin biosynthesis indirectly (via gonadoliberin) and directly. It was the objective of the present study to find out whether GABA also may influence the biosynthesis and secretion of hCG by human first trimester placenta. Already one single pulse of GABA (1 h; 0.01-100 microM) stimulated hCG secretion significantly (P less than 0.0001). GABA also induced a marked increase in the mRNA levels of both subunits, with an optimum at 10 microM. The effect on hCG secretion was mimicked by the GABA-A receptor agonist muscimol (P less than 0.002), but under the experimental conditions used (multiple pulses; 1 microM), only the beta mRNA was increased. The GABA-A receptor antagonist bicuculline (two pulses; 10 microM) suppressed basal hCG secretion (P less than 0.001) and abolished the episodic secretion pattern observed in the control cultures. Applying a combination of equimolar amounts of GABA and bicuculline, hCG secretion and the episodic secretion pattern were similar as in control cultures. The data seem to suggest a regulation of hCG biosynthesis in human first trimester placenta in which GABA is involved, probably acting via GABA-A-like receptor sites. PMID- 1309347 TI - Regulation of thyrotropin receptor gene expression in rat FRTL-5 thyroid cells. AB - TSH receptor mRNA levels in FRTL-5 thyroid cells are autoregulated at a transcriptional level by the same hormones required for the growth and function of the cells: TSH, insulin, and insulin-like growth factor-I (IGF-I). Thus, the ability of TSH, via its cAMP signal, to down-regulate steady state receptor mRNA levels is preceded by the action of TSH to decrease pre-mRNA levels in nuclear run-on assays to the same quantitative level as evident in Northern analyses. In contrast, the receptor mRNA half-life is shown not to change when down-regulation is reversed by withdrawing TSH in the presence or absence of actinomycin-D. Evidence is additionally provided that TSH receptor mRNA levels are increased by insulin, IGF-I, or calf serum in both Northern and run-on assays. This action cannot be duplicated by hydrocortisone and is evident at more than 20-fold lower concentrations of IGF-I than insulin. Moreover, insulin, IGF-I, and/or calf serum are required for the autoregulatory negative transcriptional regulation of the TSH receptor by TSH/cAMP, as is the case for thyroglobulin. This occurs despite the opposite actions of TSH/cAMP on the two genes, positive in the case of thyroglobulin and negative with TSH receptor. The positive and negative regulatory actions, respectively, of insulin/IGF-I and TSH on receptor gene expression are associated with coincident increases or decreases in cell surface receptors measured by [125I]TSH binding. The autoregulation additionally involves the interplay of a second cAMP-modulated regulatory factor, one which up regulates TSH receptor mRNA levels rather than causing down-regulation. Thus, cycloheximide inhibits the transcriptional action of both TSH/cAMP and insulin/IGF-I/serum within 4 h, i.e. a rapidly synthesized protein is an intermediate in both cases. The presence of cycloheximide for as little as 1 h, however, uncovers the ability of TSH/cAMP to increase TSH receptor mRNA levels. This activity is the result of the action of a stable cAMP-induced activator which can be detected physiologically, i.e. in the absence of cycloheximide. For example, low levels of a cAMP analog (0.2 mM), as opposed to high levels (greater than 1 mM), can increase TSH receptor RNA levels. Low levels also accelerate the insulin/IGF-I-dependent return of receptor mRNA to normal levels after TSH withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309348 TI - Paracrine communication regulates adrenocorticotropin secretion. AB - Local communication among cells of the anterior pituitary appears to play an important role in the regulation of ACTH secretion. Dissociated pituitary cells were plated as a monolayer at decreasing concentrations of cells (increasing the distance between cells and, thus, decreasing their potential interactions), and ACTH secretion was measured from individual corticotropes using a specific reverse hemolytic plaque assay. There was a critical intercell distance above which significant changes in the number of CRF-responsive corticotropes were observed. Provided that this critical distance was not exceeded the number of secretory corticotropes in response to CRF (10 nM) was relatively constant, thereby defining a fraction of corticotropes that was robustly CRF responsive. In contrast, when this critical distance between cells was exceeded, the number of CRF-responsive corticotropes progressively increased to almost double their original number, thereby defining a second fraction of CRF-responsive corticotropes that was previously repressed. These observations suggest the presence of a paracrine factor that profoundly inhibits CRF-stimulated ACTH secretion from a repressed fraction of corticotropes. Further independent studies confirmed and extended these observations. We identified the cellular source of the inhibitory factor as the robustly CRF-responsive fraction of corticotropes. Pituitary cells were identified by reverse hemolytic plaque assay and then destroyed using a laser photoablation procedure that did not compromise the remaining cells. The pituitary cells were separated by a distance at which the inhibitory factor was fully effective. Destruction of the cellular source of the paracrine inhibition would, therefore, allow secretion from the previously repressed fraction of corticotropes. Accordingly, when robustly CRF-responsive corticotropes were destroyed, a significant number of previously repressed corticotropes appeared in a second assay. Destruction of somatotropes or a cell adjacent to a robustly CRF-responsive corticotrope did not alter the number of CRF-stimulated corticotropes among the remaining cells. We conclude that a paracrine factor liberated by the robustly CRF-responsive corticotropes inhibits ACTH secretion from the repressed fraction of corticotropes. The robustly CRF responsive corticotropes appear unresponsive to the effects of the factor, and the repressed corticotropes are unlikely to secrete it. A role of this paracrine communication is to hold corticotropes in reserve and, therefore, prevent the severe depletion of hormone. This form of paracrine communication may be a specialized adaption among cells where the physiological setting demands robust secretory responses to multiple stimuli. The experimental paradigms developed here may be extremely useful for 1) screening potential paracrine factors and 2) determining whether the secretion of the paracrine factor is regulated by adrenal or hypothalamic hormones. PMID- 1309349 TI - Beta 2-adrenergic receptor mRNA is overexpressed in neoplastic human thyroid tissues. AB - The expression of beta 2-adrenergic receptor (AR) mRNA was investigated in normal and neoplastic human thyroid tissues. A combination of techniques for reverse transcribing mRNA into cDNA and the incorporation of 32P-gamma ATP into the polymerase chain reaction (PCR)-generated fragments allowed us to detect beta 2 AR mRNA in surgically excised thyroid specimens. The levels of beta 2-AR cDNA generated by PCR in thyroid adenomas and cancers were 3.3 and 6.9 times, respectively, as high as that of normal thyroid tissues. These findings suggest that the level of beta 2-AR mRNA is correlated with the extent of differentiation in neoplastic tissues. The present study provides new insights into the relationships between the AR-adenylate cyclase system and the regulation of the growth and differentiation in neoplastic human thyroid tissues. PMID- 1309350 TI - Identification of "B" receptor for natriuretic peptide in human kidney. AB - Three distinct receptor types for natriuretic peptides (NP) have been identified in human tissue. "A" and "B" receptors initiate biological actions, whereas the "C" receptor has a clearance function. It has been proposed that the natural ligand for the B receptor is c-type natriuretic peptide (CNP), rather than atrial natriuretic peptide (ANP), and that the B receptor is only found in the central nervous system (CNS) and is responsible for all NP-mediated effects in the CNS. Contrary to this hypothesis, we have identified, by means of the polymerase chain reaction (PCR), the B receptor in human kidney tissue. To detect A and C receptors, the PCR reaction was performed with primers which yielded predicted 600 and 378 base pair (bp) products, respectively. For the B receptor, 3 different primer sets were used, resulting in the expected 785, 453 and 228 bp fragments. Restriction mapping of the latter two products with Rsa I yielded the expected fragment numbers and sizes, indicating the PCR products were from B receptor mRNA. These results indicate that the human kidney has B as well as A and C receptors. Thus CNP may have a renal as well as a CNS site of action. PMID- 1309351 TI - Androgenic 17 beta-hydroxysteroid dehydrogenase activity of expressed rat type I 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase. AB - Transient expression in nonsteroidogenic mammalian cells of the rat wild type I and type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD) cDNAs shows that the encoded proteins, in addition to being able to catalyze the oxidation and isomerization of delta 5-3 beta-hydroxysteroid precursors into the corresponding delta 4-3-ketosteroids, interconvert 5 alpha dihydrotestosterone (DHT) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta diol). When homogenate from cells transfected with a plasmid vector containing type I 3 beta-HSD is incubated in the presence of DHT using NAD+ as cofactor, a somewhat unexpected metabolite is formed, namely 5 alpha-androstanedione (A dione), thus indicating an intrinsic androgenic 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity of this 3 beta-HSD isoform. Although the relative Vmax of 17 beta-HSD activity is 14.9-fold lower than that of 3 beta-HSD activity, the Km value for the 17 beta-HSD activity of type I 3 beta-HSD is 7.97 microM, a value which is in the same range as the conversion of DHT into 3 beta diol which shows a Km value of 4.02 microM. Interestingly, this 17 beta-HSD activity is highly predominant in unbroken cells in culture, thus supporting the physiological relevance of this "secondary" activity. Such 17 beta-HSD activity is inhibited by the classical substrates of 3 beta-HSD, namely pregnenolone (PREG), dehydroepiandrosterone (DHEA), delta 5-androstene-3 beta,17 beta-diol (delta 5-diol), 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) and DHT, with IC50 values of 2.7, 1.0, 3.2, 6.2, and 6.3 microM, respectively. Although dual enzymatic activities have been previously reported for purified preparations of other steroidogenic enzymes, the present data demonstrate the multifunctional enzymatic activities associated with a recombinant oxidoreductase enzyme. In addition to its well known 3 beta-HSD activity, this enzyme possesses the ability to catalyze DHT into A-dione thus potentially controlling the level of the active androgen DHT in classical steroidogenic as well as peripheral intracrine tissues. PMID- 1309352 TI - Regulation of aromatase cytochrome P-450 and 17 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels in choriocarcinoma cells. AB - In human placenta the enzyme complex aromatase catalyzes the conversion of androgens to estrogens and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mediates the reversible interconversion of, e.g. estrone to estradiol. We studied the effects of cholera toxin (CT), an activator of adenylate cyclase, and 12-O tetradecanoyl phorbol 13-acetate (TPA), a phorbol ester protein kinase C activator, on the levels of messenger (m) RNAs encoding aromatase cytochome P-450 (P-450AROM) and 17 beta-HSD in cultured JEG-3 choriocarcinoma cells. With the use of oligonucleotide probes designed according to known complementary DNA sequences, hybridizable mRNA transcripts of 3.0, 2.4, and 1.6 kilobases for P 450AROM were found in Northern blot analysis of JEG-3 cell RNA. A single 1.4 kilobase transcript was detected for 17 beta-HSD. Time-dependent increases in P 450AROM mRNA levels in JEG-3 cells were observed for both CT and TPA with maximal effects at 24-48 h. CT and TPA increased P-450AROM mRNA levels in a concentration dependent manner. The maximal effects, about 4.8-fold and 3.3-fold stimulations above basal levels, were obtained with 10 ng/ml of CT and 100 ng/ml of TPA, respectively. The effects of CT and TPA were additive. CT induced 17 beta-HSD mRNA levels in a time- and concentration-dependent manner and its maximal effect of 10.1-fold above basal levels was obtained within a similar time and concentration-dependence as for P-450AROM mRNA. TPA itself had no clear effect but it approximately doubled the effect of CT on 17 beta-HSD mRNA expression. Inhibition of protein synthesis by cycloheximide decreased basal, CT and TPA stimulated P-450AROM mRNA levels but increased the expression of 17 beta-HSD mRNA. This result is consistent with the hypothesis that induction of P-450AROM gene expression is mediated by a labile protein regulator resembling to most other steroidogenic P-450 enzymes, whereas 17 beta-HSD as a non-P450 enzyme appears to be controlled in a different manner. The present results suggest that: 1) induction of P-450AROM mRNA may at least partly be responsible for our previously reported increases in the rate of conversion of androgens to estrogens by CT and TPA in JEG-3 cells; 2) 17 beta-HSD mRNA expression is mainly controlled through a cAMP-dependent mechanism in contrast to the multifactorial control of P 450AROM mRNA; and 3) protein synthesis inhibition by cycloheximide has opposite effects on the mRNA levels of these two key enzymes in placental estrogen metabolism. PMID- 1309353 TI - The early history of the releasing factors. PMID- 1309354 TI - The conversion of corticosterone to aldosterone is the site of the oxygen sensitivity of the bovine adrenal zona glomerulosa. AB - The dissociation of renin and aldosterone observed during hypoxia in vivo has been attributed to a direct inhibition of low oxygen on adrenal zona glomerulosa function. We have demonstrated that the adrenal zona glomerulosa production of aldosterone in vitro is directly proportional to a wide range of oxygen concentrations in the physiological range but that cortisol production from coincubated fasciculata cells is not oxygen sensitive. The present study examined the hypothesis that the sensitivity to O2 is limited to the aldosteronogenic late pathway. In order to localize the site of oxygen sensitivity, we measured endogenous pregnenolone production (early pathway) and the conversion of exogenous corticosterone to aldosterone (ALDO) (i.e. 18-hydroxylase activity) in adrenal cells treated with cyanoketone (3-beta-hydroxy-steroid dehydrogenase inhibitor). Acutely dispersed bovine adrenal glomerulosa cells (four experiments in pentuplicate) were incubated under low (5%) vs. normal (21%) O2 in the presence of cyanoketone (CK; 1 microM) and/or the following: corticosterone (500 ng/ml), angiotensin II (ANG II; 10 nM), or dibutyryl cAMP (1 mM). Conversion of exogenous corticosterone to ALDO in the presence of CK was inhibited by 41 +/- 1% under low O2. This was similar to the inhibitory effect of low O2 on ANG II stimulated aldosterone production from endogenous precursors in the absence of CK (52 +/- 11% inhibition). Basal, ANG II-, and cAMP-stimulated endogenous pregnenolone production was not significantly reduced by low O2. In another experiment, glomerulosa cells were incubated under 5, 13, or 50% vs. 21% O2 in the presence of CK (1 microM) and different concentrations of corticosterone (10 1000 ng/ml). ALDO production was significantly inhibited by low O2 when corticosterone was greater than or equal to 500 ng/ml and ALDO was significantly augmented by high O2 when added corticosterone was 1000 ng/ml. We conclude that the conversion of corticosterone to ALDO (i.e. 18-hydroxylase) appears to be the primary site of oxygen sensitivity since 1) pregnenolone production was unaffected and 2) the magnitude of the inhibition of the conversion of corticosterone to ALDO by low O2 in the presence of CK was similar to the inhibition of ALDO production from endogenous precursors in the absence of CK. These studies demonstrate that oxygen sensitivity of the steroidogenic pathway is a unique, constitutive property of 18-hydroxylase, the enzyme which catalyzes the conversion of corticosterone to ALDO. We propose that the sensitivity of 18 hydroxylase to oxygen accounts for the dissociation of renin and aldosterone during hypoxia in vivo. PMID- 1309355 TI - Characterization of T lymphocytes infiltrating human pancreas allograft affected by isletitis and recurrent diabetes. AB - We studied a human leukocyte antigen-identical pancreas graft transplanted into an insulin-dependent (type I) diabetic patient shortly after onset of recurrent diabetes to characterize the putative autoreactive T lymphocytes mediating the lesion. The immunohistopathological analysis revealed the presence of isletitis and a selective loss of beta-cells. The isletitis was mostly constituted by CD8+/T-lymphocyte receptor alpha,beta (TCR alpha,beta +) T lymphocytes surrounding and infiltrating the affected islets. CD4-/CD8-/TCR gamma, delta + T lymphocytes were observed within the islets. Incubation of the tissue in 15% interleukin 2 induced the migration and initial expansion of the infiltrating cells (66% CD3+ lymphocytes) for up to 2 wk; most T lymphocytes in this initial isolate were CD4+ (92% CD4+ and 7% CD8+). Long-term anti-CD3 stimulation of this T-lymphocyte population induced the selective growth of CD8+/TCR alpha,beta + (75%) and CD4-/CD8-/TCR gamma,delta + (all V1 delta +) (17%) T lymphocytes. Therefore, this strategy selectively expanded the T lymphocytes, found to be the predominantly islet-infiltrating cells, rather than the lymphocytes predominating in the initial isolate. Anti-CD3 did not stimulate growth of T lymphocytes in cultures of three isletitis-free pancreas graft biopsies. In a control experiment with a CD4(+)-rich T-lymphocyte population, long-term anti-CD3 stimulation and cloning of cytomegalovirus (CMV)-primed peripheral blood mononuclear cells from a CMV+ subject selectively induced the growth of CD4+ T-lymphocyte clones, all CMV specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309356 TI - Dysfunction of insulin mediator protein kinase FA in lymphocytes of patients with NIDDM. AB - Patients with non-insulin-dependent diabetes mellitus (NIDDM) had an impaired capability to activate exogenous ATP.Mg-dependent protein phosphatase in lymphocytes compared with nondiabetic subjects. More importantly, the impaired protein phosphatase activation in the lymphocytes of patients with NIDDM could be consistently and completely restored to normal by exogenous pure protein kinase FA (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in patients with NIDDM is due to a functional loss of kinase FA. By contrast, both NIDDM patients and nondiabetic subjects had similar levels of total cell proteins and spontaneously active protein phosphatase activity in their lymphocytes, indicating that the dysfunction of kinase FA in patients with NIDDM is very specific. Statistical analysis further revealed that the lymphocytes isolated from 21 nondiabetic subjects contained high levels of FA activity (148 +/- 22 mU/mg cell protein), whereas, the lymphocytes of 21 patients with NIDDM contained low levels of FA activity (50 +/- 22 mU/mg), indicating statistically significant differences in FA activity between diabetic patients and nondiabetic subjects. This is the first report providing initial evidence that patients with NIDDM may statistically have a common impairment in the protein phosphatase activation in their lymphocytes and that the molecular mechanism for this defect is due to a biochemical dysfunction of protein kinase FA, a biological mediator for both insulin and epidermal growth factor. PMID- 1309357 TI - Exacerbation of experimental colitis by nonsteroidal anti-inflammatory drugs is not related to elevated leukotriene B4 synthesis. AB - The ability of nonsteroidal anti-inflammatory drugs to exacerbate experimental colitis, and the possible contributions of the "shunting" of arachidonate via the 5-lipoxygenase pathway, were investigated using a rat model in which colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid in a vehicle of 50% ethanol. Twice daily treatment with indomethacin (0.1-1 mg/kg SC) during the first week after trinitrobenzene sulfonic acid/ethanol administration resulted in dose-dependent increases in the severity of colitis and in the incidence of mortality. Mortality was not observed in vehicle-treated colitic rats or in normal rats treated with indomethacin. Similar exacerbation of colitis was observed in rats treated with naproxen (5 mg/kg). Whereas treatment with a 5 lipoxygenase inhibitor, PF-5901 (100 mg/kg PO), resulted in a significant reduction of the severity of colitis, concomitant administration of PF-5901 and indomethacin (0.5 mg/kg SC) did not inhibit the exacerbative effects of the indomethacin in this model. In separate studies, administration of indomethacin was found to significantly increase colonic myeloperoxidase activity (a measure of tissue granulocyte numbers) and suppress colonic prostaglandin E2 synthesis, while not significantly affecting colonic leukotriene B4 synthesis. The effect on myeloperoxidase activity was seen during the period 21-24 hours after trinitrobenzene sulfonic acid ethanol administration, but not during the period 45-48 hours after induction of colitis. In in vitro studies using samples of inflamed colon and in vivo studies in which colonic eicosanoid production was measured by colonic dialysis, inhibition of prostaglandin E2 synthesis was not accompanied by significant changes in leukotriene B4 synthesis. These results suggest that inhibitors of colonic prostaglandin synthesis can markedly exacerbate colitis, and that this effect is unrelated to alterations in colonic leukotriene B4 synthesis. Endogenous prostaglandins may exert anti-inflammatory effects during the acute stages of colitis. PMID- 1309358 TI - Ki-ras oncogene activation in preinvasive pancreatic cancer. AB - Activation of the Ki-ras oncogene by specific point mutations at codon 12 occurs at a remarkably high frequency in pancreatic ductal adenocarcinoma and is likely to be an important event in the pathogenesis of this cancer. To determine whether ras activation also occurs in noninvasive proliferative lesions of the pancreas, a series of cases of ductal papillary hyperplasia, intraductal papillary neoplasia, and intraduct extensions of ductal adenocarcinoma were examined for activating mutations of Ki-ras at codons 12, 13, and 61 using polymerase chain reaction amplification. Specific mutations at Ki-ras codon 12 were found in 5 of 6 cases (83%) of intraduct extensions of carcinomas and in 12 of 16 (75%) invasive carcinomas. In cases with both intraductal and invasive components, the same mutation was identified in each. No mutations were found in 5 intraductal papillary neoplasms and 9 cases of ductal papillary hyperplasia. The authors conclude that Ki-ras activation at codon 12 is important in the tumorigenesis of ductal adenocarcinoma of the pancreas but is not required in the pathogenesis of ductal papillary hyperplasia or intraductal papillary neoplasm. PMID- 1309359 TI - Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A-receptor binding. AB - Clostridium difficile toxin A, a 308-kilodalton protein exotoxin, is the principal causative agent of antibiotic-associated, C. difficile-induced colitis. In the current study, the prevalence of specific human serum and secretory antibody to toxin A and the possible protective effect of secretory, intestinal anti-toxin A antibody are examined. Serum (n = 35), colonic aspirates (n = 35), and duodenal aspirates (n = 20) were collected from adults at diagnostic endoscopy. Patients with evidence of colitis or a history of recent antibiotic use were excluded from the study. Specific serum immunoglobulin (Ig) A and IgG antitoxin A antibodies were detected in 60% and 57% of subjects, respectively, by enzyme-linked immunosorbent assay. Fifty-seven percent of colonic aspirates contained IgA antitoxin, whereas only 10% of duodenal aspirates were positive (P = 0.002). Binding of toxin A to its intestinal receptor was studied using [3H]toxin A and purified rabbit ileal brush border membranes. Toxin A binding was significantly inhibited by colonic aspirates with high IgA anti-toxin A antibody levels (0.503 +/- 0.055 pmol toxin A bound per milligram of brush border membrane protein, mean +/- SE) in comparison with antitoxin A-negative aspirates (0.778 +/ 0.089 pmol; P = 0.02) and control (0.766 +/- 0.004 pmol; P = 0.03). In the current study, a specific intestinal secretory IgA antibody response to C. difficile toxin A in humans is reported. This antibody response is more evident in the colon, the site of C. difficile infection, than in the upper intestinal tract. Our data suggest that human colonic IgA antitoxin may protect against C. difficile colitis by inhibiting the binding of toxin A to its intestinal epithelial cell receptor. PMID- 1309360 TI - Presymptomatic diagnosis of polyposis coli by DNA. PMID- 1309361 TI - Cytomegalovirus infection of the appendix in AIDS. PMID- 1309362 TI - Isolation of a neuropeptide-degrading carboxypeptidase from the human stomach. AB - The aim of this investigation was to isolate and characterize a neuropeptide degrading carboxypeptidase from the muscular and mucosal layers of the human stomach. The carboxypeptidase was solubilized from membrane preparations of gastric muscle and mucosa using Triton X-100. The detergent-solubilized enzyme was purified to apparent electrophoretic homogeneity by affinity chromatography using lisinopril or potato carboxypeptidase inhibitor as an affinity ligand. The enzyme had an apparent molecular weight of 34,300 and was bound by concanavalin A and is thus a glycoprotein. The carboxypeptidase removed C-terminal leucine, phenylalanine, or tryosine residues from peptides including angiotensin I, [Leu5]enkephalin, kinetensin, neuromedin N, neurotensin, and xenopsin. It had an alkaline pH optimum and was inhibited by lisinopril, potato carboxypeptidase inhibitor, ethylenediaminetetraacetic acid, 1,10-phenanthroline, and 8 hydroxyquinoline. Immunoblotting indicated that the gastric carboxypeptidase cross-reacted with an antibody raised against a carboxypeptidase isolated from mast cells of human skin. The gastric carboxypeptidase released from gastric mast cells upon degranulation may act to degrade and inactivate neuropeptides in the stomach wall. PMID- 1309363 TI - Intracellular calcium-mediated activation of hepatic Na+/H+ exchange by arginine vasopressin and phenylephrine. AB - The effect of Ca++ mobilizing agonists arginine vasopressin and phenylephrine on Na+/H+ exchange was studied in freshly isolated hepatocytes and isolated perfused rat livers. The activity of Na+/H+ exchange was determined from the rate of H+ efflux, 22Na uptake and pHi recovery. Arginine vasopressin and phenylephrine stimulated H+ efflux and 22Na uptake in isolated rat hepatocytes and increased the rate of pHi recovery from acid-loaded hepatocytes. These effects were inhibited by amiloride. Arginine vasopressin- and phenylephrine-induced increases in H+ efflux were also dependent on extracellular Na+. Arginine vasopressin- and phenylephrine-induced increases in intracellular Ca++ concentration, H+ efflux, 22Na uptake and intracellular pH recovery were decreased in hepatocytes preloaded with the Ca(++)-buffering agent [bis-(2-amino-5-methylphenoxy)-ethane-N,N,N',N' tetraacetic acid] (MAPTA). Na+/H+ exchange-dependent intracellular pH recovery from cytosolic acidification was stimulated by thapsigargin, which increases intracellular calcium concentration by inhibiting endoplasmic reticulum Ca++ ATPase. Arginine vasopressin- and phenylephrine-induced increases in intracellular pH recovery were not dependent on extracellular Ca++ and were inhibited by calmidazolium, a calmodulin inhibitor. Arginine vasopressin and phenylephrine also increased H+ efflux in the absence but not in the presence of amiloride in perfused rat livers without affecting biliary HCO3- excretion. These results indicate that arginine vasopressin and phenylephrine activate Na+/H+ exchange in rat hepatocytes, an effect mediated in part by intracellular Ca++ and calmodulin kinase. Furthermore, sinusoidal Na+/H+ exchange does not appear to be involved in biliary HCO3- excretion. PMID- 1309364 TI - Hepatitis C virus and organ transplantation. PMID- 1309365 TI - Improved detection of hepatitis C virus antibodies in high-risk populations. AB - Sera from 483 patients at high (group 1, n = 313) and lower (group 2, n = 170) risk for exposure to hepatitis C were tested for antibodies to hepatitis C using first-generation (c100-3) and second-generation enzyme-linked immunosorbent assays and four-antigen recombinant immunoblot assay. The second-generation enzyme-linked immunosorbent assay and nitrocellulose-based immunoblot assay differ from c100-3-based systems in the addition of expression products from the NS3/NS4 (c33c, c200) and putative nucleocapsid (c22-3) region of the hepatitis C genome. In group 1, the sensitivity of detection of hepatitis C antibodies was 45%, 55% and 46% by the first- and second-generation enzyme-linked immunosorbent assays and recombinant immunoblot assay, respectively. In group 2, antibodies were detected by each test system in 26%, 32% and 7% of patients, respectively. Most sera (99%) reactive with the first-generation enzyme-linked immunosorbent assay were reactive with the second-generation enzyme-linked immunosorbent assay (in group 1, 89% of these specimens demonstrated reactivity to at least one antigen with the immunoblot assay, compared with only 31% in group 2). An additional 12% (group 1) and 6% (group 2) of specimens demonstrated reactivity with the second-generation enzyme-linked immunosorbent assay only (of these, 75% [group 1] and 9% [group 2] demonstrated reactivity to at least one antigen with the immunoblot assay). Ninety-eight percent of specimens not reactive with both enzyme-linked immunosorbent assay test systems were also nonreactive by recombinant immunoblot assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309366 TI - Pituitary-adrenal responses to corticotropin-releasing hormone in different degrees of adrenal 21-hydroxylase deficiency. AB - 21-Hydroxylase congenital adrenal hyperplasia (21-OHCAH) involves a primary defect of the adrenal gland and a secondary involvement of ACTH secretion. The responses of the pituitary-adrenal axis to ovine CRH (oCRH, 1 micrograms/kg) were examined in subjects with different degrees of 21-OH deficiency. We studied 43 subjects: 7 classical and 6 nonclassical (NC) 21-OHCAH patients, 15 heterozygotes (HT) and 15 control subjects. Baseline plasma ACTH levels were higher in classical CAH than in NC-CAH, HT, and control subjects (mean +/- SEM, 66 +/- 14, 6 +/- 1.6, 4 +/- 0.5, and 5 +/- 0.5 pmol/L, respectively). The mean plasma ACTH response to oCRH in NC-CAH (17 +/- 3 pmol/L) was higher than in controls and HT (9 +/- 0.8 and 11 +/- 1.5 pmol/L). The highest ACTH responses to oCRH were obtained for classical CAH patients (126 +/- 29 pmol/L). Plasma cortisol rose after oCRH in control, HT, and NC-CAH patients but did not change in classical CAH. After oCRH, plasma 17-hydroxyprogesterone (17-OHP) were 4 +/- 0.5, 8 +/- 1.6, 93 +/- 28, and 359 +/- 110 nmol/L for controls, HT, NC-CAH, and classical patients, respectively. There was a significant correlation (r = 0.70) between 17 OHP and the ACTH responses to oCRH. The 17-OHP responses to oCRH were also correlated (r = 0.94) with the 17-OHP responses to the synthetic ACTH test. We conclude that the release of endogenous ACTH by oCRH result in graded 17-OHP responses on 21-OH deficiency. The present study also suggests that different degrees of adrenal biosynthetic defect may result in graded ACTH responses to oCRH. PMID- 1309367 TI - A monoclonal antibody that detects a specific human neutrophil antigen involved in phorbol myristate acetate- and formyl-methionyl-leucyl-phenylalanine-triggered respiratory burst. AB - A mouse IgM mAb termed P1E3 was raised against resting human peripheral blood neutrophils and has been shown to recognize a cell-surface Ag with an apparent molecular mass of 155 kDa, as assessed by immunoprecipitation analysis. In addition to the main 155-kDa protein, an additional band of about 210 kDa was also recognized by P1E3 in Western blot analysis. Sequential immunoprecipitation assays showed that the Ag recognized by P1E3 differed from the CD29 and CD45 Ag. However, sequential immunoprecipitation assays carried out with two distinct anti CD15 mAb and P1E3 showed that P1E3 reacted with CD15 or with a CD15-like Ag. P1E3 stained strongly resting human peripheral blood neutrophils, hardly reacted with peripheral blood monocytes and did not react with PBL and platelets, as assessed by immunofluorescence flow cytometry. P1E3 inhibited the respiratory burst induced by PMA or FMLP, but not the oxidative response induced by Con A or the calcium ionophores A23187 or ionomycin. Furthermore, P1E3 inhibited the activation of the Na+/H+ antiporter in response to PMA or FMLP and the phosphorylation of a protein of about 50 kDa in response to PMA. However, preincubation of neutrophils with P1E3 did not affect the increase in cytosolic free calcium concentration induced by FMLP. These data suggest that the Ag recognized by P1E3 may play a role in modulating the activation of the respiratory burst induced by PMA or FMLP, and that P1E3 seems to affect protein kinase C-mediated signal transduction mechanisms coupled to the induction of the respiratory burst. PMID- 1309368 TI - Neutrophil stimulation and priming by direct contact with activated human T lymphocytes. AB - The concept that T lymphocytes regulate neutrophil function has an important implication in the understanding of the role of these cells in immunity against infection and in inflammatory diseases, but evidence for this concept is primarily derived from the effects of lymphokines on neutrophils. We now present evidence to show that living or paraformaldehyde-fixed mitogen-activated T lymphocytes, as well as an activated T cell line (HUT-78), induce by cell-cell contact, an oxygen-dependent respiratory burst measured by both the lucigenin dependent chemiluminescence assay and superoxide production. Neutrophils reacted with purified human T lymphocytes which had been activated by culture in the presence of PHA and PMA for 72 h showed a marked and significant respiratory burst compared with neutrophils treated with T lymphocytes cultured in the absence of these mitogens. Similar results were observed with the paraformaldehyde-fixed T cell line (HUT-78). The ability to stimulate neutrophils required intact paraformaldehyde-fixed T cells, and neutrophil stimulation failed to occur if the T cells and neutrophils were separated by membrane filters. mAb to TNF-alpha, and TNF-beta blocked the ability of rTNF-alpha and TNF-beta to stimulate neutrophils but did not block the neutrophil response induced by activated T cells. Pretreatment of neutrophils with the activated T lymphocytes enhanced the response to the tripeptide, FMLP. It is therefore conceivable that activated T lymphocytes attracted at sites of inflammation influence neutrophil activity by direct plasma membrane interaction which clearly represents an efficient microbial defence mechanism, minimizing tissue damage during inflammation. PMID- 1309369 TI - Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation. AB - Bone marrow transplant (BMT) recipients were evaluated for subclinical varicella zoster virus (VZV) viremia and symptoms of herpes zoster after transplantation. Viremia was demonstrated by testing peripheral blood mononuclear cells using polymerase chain reaction and was documented in 19% of 37 patients. When reactivation was defined as herpes zoster and/or subclinical VZV viremia, 41% of VZV-seropositive BMT recipients experienced VZV reactivation. None of 12 patients tested before VZV reactivation had T lymphocyte proliferation to VZV antigen (mean stimulation index, 1.0 +/- 0.42 [SD] at less than 100 days; 12.0 +/- 6.03 at greater than 100 days [P = .003]). Among patients tested at greater than 100 days, 5 (63%) of 8 with detectable T cell proliferation had subclinical or clinical VZV reactivation compared with none of 6 who lacked VZV T cell responses. Recovery of VZV-specific cytotoxic T lymphocyte function was observed in 50% of BMT patients, but BMT recipients had significantly fewer circulating cytotoxic T lymphocytes that recognized VZV immediate early protein (P = .03) or glycoprotein I (P = .004) than did healthy VZV immune subjects. In vivo reexposure to VZV antigens due to subclinical VZV viremia or symptomatic VZV reactivation may explain the recovery of virus-specific T cell immunity after BMT. PMID- 1309370 TI - An experimental model for myocarditis and congestive heart failure after rabbit coronavirus infection. AB - In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2-5) and subacute (days 6-12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure. PMID- 1309371 TI - Activation of lymphocytes by varicella-zoster virus (VZV): expression of interleukin-2 receptors on lymphocytes cultured with VZV antigen. AB - The expression of human leukocyte antigen (HLA-DR) and interleukin-2 receptor (IL 2R; alpha and beta subunits) was significantly increased in peripheral blood mononuclear cells (PBMC) from varicella-zoster virus (VZV)-seropositive donors when PBMC were cultured with VZV antigen for 6 days. The increased expression of HLA-DR and IL-2R was observed in both CD4+ and CD8+ lymphocytes, which suggests that both types of lymphocytes from VZV-seropositive donors were activated when PBMC were cultured with VZV antigen. Adding anti-IL-2R alpha did not inhibit lymphocyte proliferation in response to VZV antigen, although marked inhibition was obtained by adding anti-IL-2R beta. No IL-2 was detected in the supernatant of PBMC cultured with VZV antigen; however, antibody to IL-2 inhibited lymphocyte proliferation on exposure to VZV antigen. These results indicate that IL-2 and expression of IL-2R beta are essential to lymphocyte activation by VZV antigen. PMID- 1309372 TI - Seroepidemiologic evaluation of antibodies to rotavirus as correlates of the risk of clinically significant rotavirus diarrhea in rural Bangladesh. AB - A case-control study was conducted among children and adult women in rural Bangladesh to evaluate whether serologic immunity to rotavirus was associated with a lower risk of rotavirus diarrhea of sufficient severity to cause patients to seek medical care. Acute-phase sera from 219 cases of rotavirus diarrhea, detected among patients treated in three diarrheal treatment centers, were compared with sera from 477 contemporaneously selected community controls. Overall, serum IgG antirotavirus antibody titers were nearly one-fourth as high in cases as in controls (107 vs. 417 units/ml; P less than .001). Among persons aged greater than or equal to 8 months, in whom titers of maternal antirotavirus antibodies should have been negligible, even the lowest range of detectable titers (100-200 units/ml) was associated with a substantial (75%, P less than .05) reduction of the risk of rotavirus diarrhea. We conclude that titers of serum IgG antirotavirus antibodies induced by earlier infection were inversely related to the risk of clinically significant rotavirus diarrhea. PMID- 1309373 TI - Investigation of varicella-zoster virus infection by polymerase chain reaction in the immunocompetent host with acute varicella. PMID- 1309374 TI - Effects of the spermicidal agent nonoxynol-9 on vaginal microbial flora. AB - The use of nonoxynol-9--containing vaginal contraceptive preparations increases vaginal (and urethral) colonization by Escherichia coli. Nonoxynol-9 is toxic to various microorganisms, including Lactobacillus acidophilus, but has little or no direct effect on E. coli. L. acidophilus, which is present in the vaginas of most normal women, generates H2O2 which, when combined with peroxidase and a halide, was toxic to E. coli. This toxicity was inhibited by nonoxynol-9 due to the selective destruction of the lactobacilli. In contrast, at higher concentrations, nonoxynol-9 was toxic to E. coli when combined with peroxidase and a halide. This toxicity was shared with certain other nonionic detergents and was due to the formation of peroxides in the preparations on prolonged exposure to oxygen. E. coli colonization may, in part, reflect the balance between these opposing effects of nonoxynol-9 on the vaginal antimicrobial system. Further, damage to normal tissues by peroxides in nonoxynol-9 preparations needs to be considered. PMID- 1309375 TI - Impact of Pneumocystis carinii and cytomegalovirus on the course and outcome of atypical pneumonia in advanced human immunodeficiency virus disease. AB - Patients undergoing bronchoscopy for possible pneumocystis pneumonia were studied retrospectively to characterize the impact of common viral pathogens on the course of advanced human immunodeficiency virus (HIV) disease and atypical pneumonia. In 327 episodes, Pneumocystis carinii was found in 220 (67%), cytomegalovirus (CMV) in 145 (44%), and herpes simplex virus in 16 (5%). Early deterioration in oxygenation and use of intensive care was less common in CMV positive patients. Neither CMV nor P. carinii was a predictor of mortality in multivariate analyses. CMV was not associated with an increased prevalence of later CMV disease. Isolation of CMV from the bronchoalveolar lavage fluid of these patients was not an indication for antiviral therapy. Pulmonary shedding of CMV may be associated with a decreased inflammatory response to P. carinii. The outcome of HIV-associated atypical pneumonia where no clear pulmonary pathogen is found on routine evaluation was no better than that of treated P. carinii pneumonia. PMID- 1309377 TI - The use of selective mutagenesis to study the pathogenesis of gram-positive bacterial diseases. PMID- 1309376 TI - Increased excretion of leukotriene E4 during aspirin-induced asthma. AB - The etiology of aspirin-sensitive asthma is unknown, but a plausible hypothesis is that the inhibitory effect of aspirin on the cyclooxygenase enzyme increases formation of bronchoconstrictor leukotrienes via "shunting" of unmetabolized arachidonic acid into metabolism by the 5-lipoxygenase enzyme. The severity and rapidity of bronchospasm that is induced by cyclooxygenase-inhibiting drugs in aspirin-sensitive asthmatics is directly related to the dose and to the potency of the drug to inhibit the cyclooxygenase enzyme. Since increased leukotriene synthesis has recently been shown to occur during allergen-induced asthma, we have examined whether altered leukotriene synthesis correlates with the degree of either cyclooxygenase inhibition or bronchospasm during asthma that is induced by doses of aspirin that range from 30 to 365 mg in individual patients. Excretion of leukotriene E4 was increased by a mean of 361% +/- 76% (p less than 0.05) during aspirin-induced asthma episodes, but the degree of increase for individual patients did not correlate with the degree of bronchospasm or inhibition of platelet thromboxane B2 formation. Thus although the endogenous synthesis of potent bronchoconstrictor leukotrienes increases during aspirin-induced bronchospasm, it appears unlikely that a direct "shunting" of unmetabolized arachidonate into leukotriene synthesis represents the mechanism of aspirin induced asthma. PMID- 1309378 TI - Gp-regulated phosphoinositide hydrolysis in turkey and human erythrocytes exposed to fluoride ion: relationship to calcium influx. AB - Previous studies have demonstrated that although both mammalian and avian erythrocytes express an inducible inositol bisphosphate-specific phospholipase C, only the latter possess the guanine nucleotide-binding protein (Gp) that regulates this activity. In confirmation of previous reports, turkey erythrocyte plasma membranes responded to guanosine 5'-0-(3-thio)triphosphate (GTP-gamma-S) and fluoroaluminates with hydrolysis of phosphoinositides, release of inositol phosphates, and generation of diacylglycerol, whereas human erythrocyte plasma membranes exhibited no such changes when incubated with known activators of guanine nucleotide regulatory proteins. We next contrasted responses of intact turkey and human erythrocytes to fluoroaluminates to develop a model to investigate the cellular effects of Gp activation. When turkey erythrocytes were exposed to fluoroaluminates, cellular levels of diacylglycerol and phosphatidic acid rapidly increased as phosphoinositides were hydrolyzed. The alterations in the lipid composition of turkey erythrocytes effected by fluoroaluminates were remarkable; phosphatidic acid levels increased over 30-fold, whereas levels of polyphosphoinositides were decreased to less than 10% of those present before stimulation. In contrast, fluoroaluminates caused only minor alterations in the diacylglycerol and phospholipid content of intact human erythrocytes. To define the role of inositol-specific phospholipase C activation in the transmembrane conveyance of extracellular Ca++, we compared the influx of extracellular Ca++ in human and turkey erythrocytes exposed to fluoroaluminates. Fluoroaluminates initiated a sustained influx of extracellular 45Ca++ into turkey, but not human, erythrocytes. These results provide strong support for the hypothesis that Gp activation results in an influx of calcium into stimulated cells. Moreover, the data demonstrate that comparison of responses of human and turkey erythrocytes to fluoroaluminates provides a well-defined method for investigating the mechanisms and consequences of Gp activation in intact cells. PMID- 1309379 TI - Acute lymphoblastic leukemia occurring as a second malignant neoplasm in childhood: report of three cases and review of the literature. AB - PURPOSE: The long-term effects of childhood cancer and its therapy are a problem of increasing concern. One of the most important of these late effects is the development of second malignant neoplasms (SMNs), which occur in approximately 8% of children within 20 years of diagnosis of a malignancy. These secondary cancers may result (individually or in combination) from increased genetic susceptibility, the mutagenic effects of chemotherapy and/or radiation therapy, or chance. Whereas the development of acute nonlymphocytic leukemia (ANLL) as an SMN is a well-recognized phenomenon, acute lymphoblastic leukemia (ALL) has been infrequently described as an SMN in either adults or children. PATIENTS AND METHODS: We report three patients treated at our institution in whom ALL developed as an SMN after treatment for neuroblastoma, Wilms' tumor, and Hodgkin's disease. These cases prompted us to review the published literature for cases of secondary ALL in childhood. Patients whose initial malignancy was diagnosed at age less than 16 years were classified as pediatric patients. SMNs were defined as cancers of clearly distinct histologic type occurring 6 or more months after diagnosis of the first malignant neoplasm. RESULTS: Including the three index cases, a total of 18 children with secondary ALL are reviewed, and the clinical features are discussed and compared with those of secondary ANLL. CONCLUSIONS: This review summarizes the published case histories of secondary ALL. The data suggest that ALL represents approximately 5% to 10% of the cases of acute leukemia that arise as SMNs in both adults and children. PMID- 1309380 TI - A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. AB - PURPOSE: Camptothecin-11 (CPT-11) is a new semisynthetic derivative of CPT, and has been shown to inhibit DNA topoisomerase I and to have a strong antitumor activity with low toxicity in murine tumors. To evaluate the effectiveness of CPT 11 in patients with non-small-cell lung cancer (NSCLC), a phase II study was conducted between April 1989 and February 1990. PATIENTS AND METHODS: Seventy three patients were entered onto the study. All patients had had no previous therapy and had measurable disease. Their median age was 67 years (range, 34 to 75 years). Fifty-four patients had a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale, and 19 had a PS of 2. CPT-11 was given at a dose of 100 mg/m2 by intravenous 90-minute infusion once a week. The dose of CPT-11 was modified based on the WBC count obtained on the day of drug administration. RESULTS: Of 72 assessable patients, 23 (31.9%) showed a partial response (95% confidence interval, 20.2% to 43.6%). Of 40 patients with a stage IV disease, 13 (32.5%) responded. Response rates for patients with PS 0 or 1 and those with PS 2 did not differ (34.0% and 26.3%, respectively). The median duration of response in patients showing a PR was 15 weeks. The median survival time for all patients was 42 weeks. The major toxicities were leukopenia and diarrhea. Grade 3 or 4 leukopenia and diarrhea occurred in 18 patients (25%) and 15 patients (21%), respectively. These toxicities were unpredictable. Other toxicities of greater than or equal to grade 3 included nausea/vomiting (22%), anemia (15%), alopecia (4%) and pneumonitis (3%). One patient died of pulmonary toxicity (interstitial pneumonitis). CONCLUSIONS: CPT-11 is a very active agent for NSCLC with acceptable toxicities. Further trials in combination with other agents for this disease are warranted. PMID- 1309381 TI - Cushing's syndrome associated with ectopic corticotropin production and small cell lung cancer. AB - PURPOSE: This study was undertaken to review the clinical and laboratory features and response to treatment of patients with Cushing's syndrome associated with ectopic corticotropin (adrenocorticotropic hormone; ACTH) production and small cell lung cancer (SCLC). PATIENTS AND METHODS: We undertook a retrospective chart review of 545 patients with SCLC seen at Toronto General Hospital between 1980 and 1990 and identified 23 patients (4.5%) with Cushing's syndrome and ectopic ACTH production. RESULTS: There were 17 male and six female patients, with a median age of 60 years. The syndrome was diagnosed at the time of initial presentation of SCLC in 13 patients and at relapse in 10 patients. Seven patients had limited disease and 16 had extensive disease at their initial diagnosis of SCLC, but 20 of 23 had extensive disease at the time of diagnosis of Cushing's syndrome. Ten patients had bone marrow involvement. The most frequent physical findings included edema (83%) and proximal myopathy (61%). All patients had elevated plasma and urinary free cortisol levels; 22 had a hypokalemic alkalosis, and 13 had hyperglycemia. Only one patient had a normal ACTH level. The response rate (complete plus partial) to chemotherapy for patients who had the syndrome diagnosed at initial presentation of SCLC was only 46%, and their median survival was only 3.57 months. Only two patients achieved complete normalization of all hormone parameters, and neither experienced hormone relapse at the time of SCLC relapse. Complications of therapy included gastrointestinal (GI) ulceration (six patients), GI bleeding (four), perforation of a duodenal ulcer (one), pneumonia (10), septic shock (three), and fungal infections (five). CONCLUSION: Ectopic ACTH production is associated with a low response to chemotherapy, short survival, and a high rate of complication to therapy. PMID- 1309382 TI - Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study. AB - PURPOSE: The Testicular Cancer Intergroup Study (TCIS) was undertaken to evaluate the pathologic findings in early-stage testicular cancer as determined by central pathology review, to compare these findings with the interpretation by the contributing pathologists, and to make correlations with various clinical parameters and outcomes. PATIENTS AND METHODS: The prospective study of non seminomatous germ cell testicular cancer staged surgically involved 459 eligible patients with stage I (node-negative) or stage II (node-positive) disease. Pathologic materials from both the orchiectomy and lymphadenectomy specimens were submitted to a central laboratory for evaluation. RESULTS: Central and local pathologists differed significantly in their identification of certain cellular histologies (primarily yolk sac tumors [YST]) and recognition of invasion into vascular structures. In contrast to our prior findings with local pathologic assessment, venous/lymphatic invasion as determined by central review predicted relapse in both stages. In pathologic stage I disease, the relapse rate was 19.4% (12 of 62 cases) for those with invasion versus 6.0% (10 of 168 cases) for those without invasion. In pathologic stage II disease, the respective relapse rates were 63.5% (40 of 63 cases) and 24.0% (six of 25 cases). Vascular invasion was jointly predictive with nodal stage for risk of relapse. The percentage of embryonal carcinoma (EC) in the primary tumor was predictive of nodal stage and relapse in a univariate, but not a multivariate, analysis. In a large substudy, immunohistochemical staining identified a correlation between stain intensity in YST and serum alpha-fetoprotein (AFP) levels. In a similar fashion human chorionic gonadotropin (HCG) staining reactivity occurred exclusively in patients with syncytiotrophoblasts and correlated with serum levels of beta-HCG. CONCLUSIONS: A number of tumor histology correlates with clinical parameters have been identified or confirmed. Careful pathologic scrutiny of the primary testicular tumor, especially for vascular invasion, provides important prognostic information. PMID- 1309384 TI - Determination of fixed charge density in cartilage using nuclear magnetic resonance. AB - Many biomechanical and chemical properties of cartilage are dependent on the fixed charge density (FCD) of the extracellular matrix. In this study, nuclear magnetic resonance (NMR) spectroscopy was investigated as a nondestructive technique for determining FCD in cartilage. Sodium content was measured by NMR in cartilage explants and was compared with sodium content measured by inductively coupled plasma emission spectroscopy (ICP) in order to verify the total NMR visibility of sodium in cartilage. The ratio of NMR to ICP results was 1.02 +/- 0.04 (calf, mean +/- SD, n = 7) and 1.04 +/- 0.11 (adult bovine, n = 8). Sodium concentration as measured by NMR was then used with ideal Donnan theory to compute estimates of FCD. For calf articular cartilage (AC) near physiological conditions, calculated FCD was -0.28 +/- 0.03 M (n = 10). NMR measurements were then made for individual cartilage specimens sequentially equilibrated in baths of differing salt composition, pH, or ionic strength. For calf and adult AC, calculated FCD decreased dramatically between pH 3 and 2, with adult specimens becoming positively charged but calf tissue retaining a net negative charge. For calf AC equilibrated in 0.3-0.015 M NaCl, calculated FCD was observed to decrease slightly with decreasing bath ionic strength. For epiphyseal cartilage, FCD varied with the position of origin of the explant within the joint, ranging from 0.19 to -0.35 M in a manner that correlated with tissue glycosaminoglycan content. Preliminary NMR imaging experiments demonstrated similar variations of sodium concentration in intact ulnar epiphyseal cartilage. Collectively, these results demonstrate the ability of NMR to nondestructively follow FCD in cartilage. The technique is applicable to dynamic studies as well as to both in vitro and in vivo studies on living tissue. PMID- 1309383 TI - The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party. AB - PURPOSE: To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS: Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS: With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS: The first four factors were used to define a simple prognostic classification. A good prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials. PMID- 1309385 TI - The effect of hypothermic ischemia on the alpha-adrenergic mechanisms of the canine tibia vascular bed. AB - The effect of hypothermic ischemia on alpha-1 and -2 adrenergic receptor mediated vasoconstriction has been studied in an in vitro perfused canine tibia preparation. Bones were perfused at a constant rate with aerated (95% O2, 5% CO2) modified Krebs Ringer solution and the effect of bolus injections of norepinephrine (0.025-6.4 nmol) on the perfusion pressure was studied. For all bones the first dose-response curve was produced under control conditions. In one group the second dose-response curve was generated during a constant infusion of prazosin (alpha-1 adrenergic antagonist); in another it was produced during a constant infusion of rauwolscine (alpha-2 adrenergic antagonist); in the control group it was generated under control conditions. The results demonstrate that, after 48 h of hypothermic ischemia, alpha-1 adrenergic-mediated vasoconstriction was significantly attenuated (p less than 0.001). However, alpha-2 adrenergic mediated vasoconstriction was unaffected by increasing periods of hypothermic ischemia. PMID- 1309387 TI - Pertussis hospitalizations and mortality in the United States, 1985-1988. Evaluation of the completeness of national reporting. AB - OBJECTIVE: --To determine the magnitude of hospitalizations for pertussis and pertussis mortality and to estimate the total burden of clinically significant pertussis in the United States. DESIGN: --Capture-recapture methods for estimating population size from independent surveillance systems were used to analyze morbidity and mortality data from case report forms received at the Centers for Disease Control (CDC) from the states, and compared these data with pertussis hospitalizations compiled from a database of US hospitals participating in the Commission on Professional and Hospital Activities-Professional Activities Survey (CPHA-PAS) and death certificate reports compiled by the National Center for Health Statistics (NCHS). POPULATION STUDIED: --All pertussis hospitalizations and pertussis-related deaths in the United States, 1985 through 1988. RESULTS: --We estimated that 13,557 pertussis hospitalizations (95% confidence interval [CI], 12,953 to 14,162) and 98 pertussis deaths had occurred during the 4-year study period (an average of more than 3300 hospitalizations and 25 deaths per year). The completeness of reporting hospitalizations to the CDC was 32% and to the CPHA-PAS, 23%, while the completeness of reporting pertussis deaths to the CDC was 33% and to NCHS, 23%. Patients who were hospitalized with pertussis and reported to CDC were at a higher risk for developing pneumonia (31.0% vs 20.0%, relative risk [RR], 1.6; 95% CI, 1.4 to 1.7), seizures (3.7% vs 2.1%; RR, 1.9; 95% CI, 1.4 to 2.5) and encephalitis (1.2% vs 0.2%; RR, 5.3; 95% CI, 2.4 to 11.6) compared with patients recorded in the CPHA-PAS system. CONCLUSIONS: --Our study suggests that there is substantial underreporting of pertussis, that severe complications of pertussis (including hospitalizations) are reported preferentially to the CDC, and that the national health impact of pertussis based on these indicators is considerably higher than previously published reports have suggested. PMID- 1309386 TI - Fibronectin and keratan sulfate synthesis by canine articular chondrocytes in culture is modulated by dibutyryl cyclic adenosine monophosphate. AB - The ability of cyclic adenosine monophosphate (cAMP) to maintain differentiated properties of canine articular chondrocytes in culture is reported. Treatment with 0.5 mM dibutyryl cAMP (DBcAMP) caused the cells to adopt a more rounded morphology. This change in morphology seems to have no effect on the overall biosynthetic rates of the cells. After a pulse with 35S-methionine, there was no difference in the concentration of labeled proteins between cultures treated with DBcAMP and control cultures. After 6 days, the amount of fibronectin (FN) in the media of DBcAMP-treated cultures detected by an enzyme-linked immunosorbent assay was specifically reduced by 30%. The amount of 35S-FN purified by gelatin affinity chromatography decreased 33%. Moreover, the percentage of FN containing the extra domain A sequence was reduced from 19.4 +/- 8.7% in control cultures to 9.6 +/- 4.2%. Concomitant with the decrease in FN, there was an increase in the concentration of keratan sulfate in the media of DBcAMP-treated cultures. After 6 days, treated cultures had 47% more keratan sulfate than controls did. These changes appear not to be the result of a change in the deposition of FN or keratan sulfate, because the amount of these molecules that could be extracted from the cell layer was typically below the limit of detection of the assays. Instead, it seems there is a phenotypic change in the chondrocytes pertaining to the production of FN and keratan sulfate. PMID- 1309388 TI - Extension of public comment period for revision of HIV infection classification system and expansion of AIDS surveillance case definition. PMID- 1309389 TI - The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. AB - BACKGROUND: Suppression of pituitary-adrenal function is a well-known consequence of glucocorticoid therapy, manifested principally by decreased corticotropin secretion. To determine the degree of suppression of pituitary-adrenal function in patients treated with different doses of synthetic glucocorticoid medication for different periods, we measured the pituitary-adrenal response to the administration of exogenous human corticotropin-releasing hormone (CRH). METHODS: We studied 279 patients who were receiving daily therapy with 5 to 30 mg of prednisone or its equivalent to treat various chronic diseases, principally collagen vascular disorders, and 50 normal subjects. Therapy ranged in duration from 1 week to 15 years. Stimulation tests using 100 micrograms of CRH as a bolus injection were performed in the morning, 24 hours after the most recent dose of glucocorticoids. In 61 patients an insulin hypoglycemia test, thought by many to be the reference standard, was also performed to assess the reliability of the CRH results. RESULTS: After the administration of CRH, 43 patients had no increase in plasma concentrations of corticotropin and cortisol. The response was blunted in 133 patients and normal in 103. There was poor correlation between the plasma cortisol response after the administration of CRH and the dose or duration of therapy or the basal plasma cortisol concentration. Although plasma cortisol concentrations after stimulation with CRH were generally lower than those after insulin administration, there was a significant correlation between the plasma cortisol responses to the two stimuli (r = 0.82). CONCLUSIONS: Pituitary-adrenal function in patients treated with synthetic glucocorticoids cannot be reliably estimated from the dose of glucocorticoid, the duration of therapy, or the basal plasma cortisol concentration. In such patients, testing with CRH is nearly as useful as insulin hypoglycemia testing in the assessment of pituitary-adrenal function. PMID- 1309390 TI - Efficacy of low oral doses of iodized oil in the control of iodine deficiency in Zaire. AB - BACKGROUND: About one billion people worldwide are at risk for iodine deficiency. Despite existing programs of prophylaxis, the prevention of iodine deficiency is still a challenge throughout the developing world. We studied the efficacy of low doses of iodized oil in an area of severe iodine deficiency in Zaire. METHODS: Seventy-five subjects with visible goiter were randomly assigned to receive a single oral dose of placebo or either 0.1 or 0.25 ml of iodized oil, corresponding to 0, 47, and 118 mg of iodine, respectively. The mean ages of the subjects in the three groups were 23, 22, and 22 years, respectively, and the ratios of males to females were 0.25, 0.32, and 0.19. Efficacy was assessed by evaluating goiter size and measuring urinary iodine and serum thyroid hormone concentrations for 12 months. RESULTS: Goiter size decreased in most of the subjects who received either dose of iodized oil. Their urinary iodine concentrations were normal for six to nine months and their serum thyroxine and thyrotropin concentrations were nearly all normal throughout the study period. There were no side effects, even in subjects whose serum thyroxine concentrations had initially been low. In the placebo group, neither goiter size nor any of the biochemical values changed. CONCLUSIONS: The oral administration of a single small dose of iodized oil is capable of correcting iodine deficiency for about a year. This method of supplementation is likely to be more effective, efficient, and acceptable than the administration of either intramuscular or large oral doses of iodized oil. PMID- 1309392 TI - Iodine deficiency--the next target for elimination? PMID- 1309391 TI - The treatment of cytomegalovirus in AIDS--more than meets the eye. PMID- 1309393 TI - Serology versus clinical signs or symptoms and main laboratory findings in the diagnosis of exanthema subitum (roseola infantum). AB - Twenty-five patients with clinical exanthema subitum (roseola infantum) were enrolled into a study, where acute-phase and convalescent sera were examined for antibodies to human herpesvirus 6 (HHV-6), several other viruses, and other microbes. In addition, an acute-phase fecal specimen was examined for viruses by electron microscopy. Confirmative or suggestive serologic evidence for recent HHV 6 infection was obtained in 23 (92%) cases. Conversion to HHV-6 was found in 19 (76%), a diagnostic (greater than or equal to 4-fold) titer rise in 2, a twofold titer rise in 1, and a stable relatively high titer in 1 of the patients; only 2 (8%) individuals remained negative. The other microbial assays produced only two slight mycoplasma antibody rises and one rotavirus identification in the fecal specimen. It is concluded that if the clinical diagnosis of exanthema subitum is deemed doubtful, HHV-6 infection is verifiable in about 75% of the cases by serology. PMID- 1309394 TI - Viremic phase in a leukemic child after live varicella vaccination. PMID- 1309395 TI - Herpes simplex virus in childhood erythema multiforme. AB - Although an association between herpes simplex virus (HSV) infection and erythema multiforme (EM) minor has been documented in adults, this has not been reported in the pediatric population. This study assessed the potential role of HSV infection in the pathogenesis of EM minor in children. Erythema multiforme skin lesions from 20 children, aged 1 to 16 years, were examined for the presence of HSV by using the polymerase chain reaction. The children included all fit strict clinical criteria for EM minor. Ten had a clinical history of an antecedent herpes infection ("herpes-associated EM"), and 10 did not ("idiopathic EM"). Herpes simplex virus DNA was detected in skin lesions of 8 of 10 children with herpes-associated EM and in 8 of 10 with idiopathic EM. Control skin biopsies from children with other bullous inflammatory diseases were negative. In addition, no HSV could be detected in a biopsy of normal uninvolved skin of a child in whom HSV was present in lesional skin. In situ hybridization on selected biopsies by means of an HSV-specific riboprobe confirmed the presence of HSV and localized it to the epidermis. It is concluded that HSV is a significant precipitating factor for EM minor in children, as it is in adults, and that clinicians should maintain a high index of suspicion of HSV even in the absence of a known history of herpes infection. PMID- 1309396 TI - Nuclear receptors, transcriptional regulation, and oncogenesis. PMID- 1309397 TI - Dietary arginine influences Rous sarcoma growth in a major histocompatibility B complex progressor genotype. AB - L-Arginine (L-Arg) can serve as a substrate for the production of reactive nitrogen intermediates. One of these metabolites, nitric oxide, has been shown to possess significant antitumor properties in vitro. To investigate the importance of this system in vivo, we have examined the dietary L-Arg host tumor interaction in the chicken. Since chickens are incapable of de novo L-Arg synthesis, concentration of this amino acid is readily controlled by diet. Line UNH 105 New Hampshire chickens having the major histocompatibility complex genotype, B24/B24, were used to study in vivo effects of dietary L-Arg on Rous sarcoma growth. After 5 weeks on a standard diet, 119 chicks were fed either a basal (0.92% L-Arg) diet or a high arginine (2.40% L-Arg) diet. One week later, chicks were wing-web inoculated with subgroup A Rous sarcoma virus. Tumor growth was monitored weekly for 12 weeks after inoculation. Plasma L-Arg levels and body weights from birds on each dietary treatment were analyzed. Neither body weight gains nor latent period for tumor development was affected by diet. However, plasma L-Arg levels were significantly different between dietary treatments (basal, 0.245 +/- 0.01 mumol/ml; high, 0.738 +/- 0.03 mumol/ml). In addition, mean tumor size scores were significantly (P less than 0.05) lower over time in chickens fed the high L Arg diet. The results suggest that dietary L-Arg in excess of the amount required for growth reduces tumor load. PMID- 1309398 TI - Enhanced growth of Legionella pneumophila in tetrahydrocannabinol-treated macrophages. AB - Legionella pneumophila is an opportunistic intracellular pathogen that infects macrophages, both in vivo and in vitro. Tetrahydrocannabinol is a major psychoactive component of marijuana and can affect the functional activity of macrophages. In the present study, it was found that the treatment of macrophage cultures from permissive A/J mice with THC enhanced the growth of Legionella in these cells. Legionella grew much better in macrophages treated with low doses of THC, which caused no alteration in the number or viability of macrophages, as compared with growth in untreated cells. Furthermore, lipopolysaccharide-treated A/J mouse macrophages restricted the growth of Legionella, but this growth restriction was overcome by the addition of THC to LPS-treated macrophage cultures after infection. Thus, it is apparent that THC has the ability to enhance the growth of the intracellular opportunistic pathogen Legionella that grows in A/J mouse macrophages. PMID- 1309399 TI - Effect of tumor necrosis factor on enzymes of gluconeogenesis in the rat. AB - The effect of human recombinant tumor necrosis factor (TNF)-alpha on enzymes of gluconeogenesis in the rat was investigated by determining the activity of glucose 6-phosphatase, fructose 1,6-diphosphatase (FDP), and phosphoenolpyruvate carboxykinase in the liver and kidney of fed and fasted rats. The activity of transaldolase in the pentose phosphate pathway was also measured. Starvation of rats for 24 hr resulted in a 1.6- to 3.1-fold increase in liver and kidney glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (P less than or equal to 0.05), a decrease in liver and kidney FDP (P less than 0.002), and an increase in liver and kidney transaldolase (P = 0.0001). Injection of 50 and 100 micrograms/kg/day of TNF for 5 days resulted in a significant (P less than or equal to 0.03) decrease in kidney FDP only. Injection of 100 micrograms/kg/day of TNF for 5 days with a 24-hr fast on Day 5 resulted in a significant (P = 0.04) increase in liver transaldolase, and a significant decrease in kidney FDP and phosphoenolpyruvate carboxykinase. Comparison of the enzyme activities of rats injected with 100 micrograms/kg/day of TNF for 5 days with those of their pair fed control partners revealed additionally a significant decrease in glucose 6 phosphatase in the liver (P less than 0.001). It is concluded that TNF administration in the rat has different effects on the enzymes of gluconeogenesis in the liver and kidney, and these effects differ from those seen in starved or tumor-bearing rats. PMID- 1309400 TI - The structure of the guanine cation: ESR/ENDOR of cyclic guanosine monophosphate single crystals after X irradiation at 10 K. AB - Following X irradiation of 3',5'-cyclic guanosine monophosphate single crystals at 10 K, several free radicals were trapped and detected by ESR/ENDOR/FSE spectroscopy. The two dominant species both have unpaired spin located on the guanine base. One is the product of net hydrogen atom loss from the exocyclic amino group. The spectroscopic characteristics of this resonance leave this assignment unambiguous. The experimental conditions make it likely that this species was formed by deprotonation of the guanine base cation. The nature of the other species is more uncertain. However, the evidence is consistent with the assignment that it is a net OH adduct to the C4 position of the base. Several species in which the unpaired spin was located on the sugar-phosphate region of the molecule were also observed. The mechanisms for the decay of the primary radicals, also leading to the well-known C8 hydrogen addition radical of the guanine base, are described and discussed. PMID- 1309401 TI - The flexible choledochoscope and tumor removal. PMID- 1309402 TI - Synergism between leukotriene B4 and thromboxane A2 in mediating acid-aspiration injury. AB - Acid aspiration leads to thromboxane-dependent lung neutrophil sequestration associated with microvascular permeability increase. Leukotriene B4 (LTB4) is postulated to be a cofactor in the thromboxane-induced inflammatory response. This study tests the interaction between LTB4 and thromboxane, focusing on LTB4 induction of thromboxane-dependent lung neutrophil sequestration after acid aspiration. Anesthetized rats underwent tracheostomy and insertion of a cannula in a left lung segment. This was followed by instillation of either 0.1 ml 0.1N hydrochloric acid (n = 18) or 0.1 ml saline in control rats (n = 18). When assayed at 3 hours, acid aspiration led to increased plasma levels of LTB4 and thromboxane B2 (TxB2), higher than control values (p less than 0.05). The rise in plasma LTB4 was correlated (p less than 0.05; r = 0.83) with sequestration of neutrophils in the nonaspirated lung. The entrapment of thromboxane-dependent lung neutrophil was associated with an increase in protein concentration in bronchoalveolar lavage of the aspirated and nonaspirated sides and an increase in lung wet to dry weight ratio. Pretreatment of other rats (n = 18) with the lipoxygenase inhibitor diethylcarbamazine IV prevented an aspiration-induced rise in plasma LTB4 and TxB2. Further, there was an attenuation of lung leukosequestration and protein leak in bronchoalveolar lavage and lung edema (all p less than 0.05). Pretreatment of other rats (n = 12) with the leukotriene receptor antagonist FPL 55712 IV did not prevent the aspiration-induced rise in LTB4 or TxB2, but otherwise was as effective as diethylcarbamazine in preventing injury. Finally, other hydrochloric acid-aspirated rats (n = 8) were pretreated intravenously with the thromboxane synthetase inhibitor OKY 046 or the thromboxane receptor antagonist SQ 29548. Both agents limited the aspiration induced rise in plasma LTB4 (p less than 0.05). The data indicate that localized acid aspiration induces synthesis of LTB4 and thromboxane A2. Inhibition of either leukotriene or thromboxane will limit PMN adhesion and increased lung permeability. PMID- 1309403 TI - Evaluation and follow-up of abnormal Pap smears. AB - An estimated 13,500 cases of invasive cervical cancer and 6,000 related deaths occur each year in the United States. These numbers can be significantly reduced if all women are regularly screened with Papanicolaou (Pap) smears and undergo colposcopy when abnormalities are detected. Screening with Pap smears should begin at age 18 or at the age of first sexual intercourse and should be repeated every one to three years, depending on individual risk factors, until age 65. Screening may be discontinued in women over age 65 who have had normal findings on two consecutive Pap smears. Risk factors for cervical cancer include sexual intercourse before age 20, more than two sexual partners in a lifetime, cigarette smoking and genital human papillomavirus (HPV) infection. Use of a spatula and Cytobrush for cervical sampling will improve the chances of collecting an adequate sample containing endocervical cells. Family physicians must know the significance of various cervical abnormalities reported by the laboratory. In women with cervical or genital HPV infection and persistent inflammatory cervical changes unresponsive to appropriate therapy, colposcopy is necessary to screen for underlying dysplasia. PMID- 1309404 TI - Acute hemorrhagic conjunctivitis. AB - Acute hemorrhagic conjunctivitis, an infection caused by enterovirus 70 and a variant of coxsackievirus A24, is characterized by the rapid onset of severely painful conjunctivitis and subconjunctival hemorrhage. The condition is usually benign and resolves in five to seven days; however, a polio-like paralysis (radiculomyelitis) develops in approximately one in 10,000 patients infected with enterovirus 70. No treatment is available. Information about acute hemorrhagic conjunctivitis should be provided to patients and the community in order to prevent undue alarm, discourage home remedies and control the spread of this highly contagious disease. PMID- 1309405 TI - Is necrosis induction therapy relevant to hepatocellular carcinoma? Prognostic evaluation viewed from necrosing feature in HCC occluding the main portal vein after treatment with DBcAMP and MMC. AB - Intraarterial infusion therapy combining dibutyryl adenosine 3',5'-monophosphate and mitomycin C was administered to 27 patients with hepatocellular carcinoma (HCC) occluding the main portal vein. Twelve patients (44%) survived more than 6 months, among them nine (75%) whose tumors were non-necrosing before treatment. When patients were compared for the presence or absence of necrosis in the tumor, those with necrosis responded poorly to treatment; only 3 of 11 (27%) survived more than 6 months. Although the combination therapy exerted a salutary effect on HCC occluding the main portal vein, the presence of necrosis in the tumor was an unfavorable sign for the prognosis, which casts doubt upon the use of the necrosis-inducing method for the treatment of HCC. PMID- 1309406 TI - Rapid growth and difficulty of early detection of scirrhous carcinoma of the stomach. AB - We report six cases of scirrhous carcinoma of the stomach in which we were able to observe the natural history of serial radiographs. All the patients developed scirrhous carcinoma of the stomach in an observation periods ranging from 2 to 15 months (mean: 5.8 months). No abnormalities or obvious findings indicative of a carcinoma were detectable, on the prior radiographs, even when they were reviewed. Endoscopy was also performed in two patients during the observation period, and no lesions were detected. At the time of diagnosis, two patients were inoperable because of metastases and died of the disease 2 and 5 months later. Three patients died of the disease 5, 8, and 26 months after gastrectomy, respectively. Only one patient is free of disease 16 months after gastrectomy. Our findings suggest that the difficulty of detection and the rapid growth of this tumor may explain why it is seldom detected at an early stage and has a very poor prognosis. PMID- 1309407 TI - Effect of dietary fiber on total carbohydrate losses in ileostomy effluent. AB - Studies were performed in three ileostomate subjects to determine the effect of intake of various carbohydrate-containing foods on the ileostomy losses of macronutrients. The percent recovery of available carbohydrate in ileostomy effluent varied between 1.09% and 22.63% for the various foods. Available carbohydrate recovery (%) was positively correlated with fiber (r = 0.91) and protein (r = 0.46) intake, but negatively with available carbohydrate intake (r = -0.66). Stepwise regression indicated that dietary fiber intake was the principal factor determining the amount of available carbohydrate in ileostomy effluent. Fiber intake was negatively correlated with water concentration of the effluent (r = -0.61). This study demonstrates that although fiber has been considered the chief substrate available for colonic fermentation, as the fiber intake increases, so the total fermentable load entering the colon is likely to increase due to losses of available carbohydrates in addition to fiber. Simple assessment of dietary fiber is likely to grossly underestimate the fermentable load on high fiber, high-carbohydrate diets. PMID- 1309408 TI - Simultaneous herpes simplex types 1 and 2 keratitis in acquired immunodeficiency syndrome. PMID- 1309409 TI - Repair of retinitis-related retinal detachments with silicone oil in patients with acquired immunodeficiency syndrome. AB - To provide prompt visual rehabilitation and to reduce the need for repeated operations, we performed vitrectomy with silicone oil tamponade in 16 consecutive eyes with retinal detachments related to cytomegalovirus retinitis and acute retinal necrosis in 13 patients with acquired immunodeficiency syndrome. In all 16 eyes (100%), retinas were reattached with one operation. Preservation of ambulatory vision was achieved in six of eight eyes (75%; mean follow-up, 14.6 weeks). No patient with hand motion visual acuity or worse preoperatively recovered ambulatory vision. Visual acuity recovery was limited by optic nerve disease in five eyes (31%). Silicone oil-related side effects did not adversely affect visual outcome in any eye. Six patients (46%) have since died (mean, 4.4 months postoperatively). These data indicated that successful surgical repair of these detachments can be consistently achieved with this approach. The prognosis for ambulatory vision is strongly related to preoperative visual acuity. PMID- 1309410 TI - Efficacy and safety of nedocromil sodium ophthalmic solution in the treatment of seasonal allergic conjunctivitis. AB - To assess the efficacy and safety of twice-daily administration of nedocromil sodium 2% ophthalmic solution, we performed a multicenter study involving 140 patients with seasonal allergic conjunctivitis. Subjects had a history of seasonal allergic conjunctivitis and positive results of a skin test to ragweed. The trial coincided with the peak ragweed pollen season at five treatment centers. Patients treated with nedocromil sodium had improvements in symptoms with statistically significant reductions recorded for eye itching (P less than or equal to .04), conjunctival injection (P less than or equal to .001), and overall disease severity (P less than or equal to .001) as compared to the placebo-treated group. Adverse events were minor and transient. We concluded that nedocromil sodium 2% ophthalmic solution administered twice daily is effective in relieving major symptoms associated with seasonal allergic conjunctivitis. PMID- 1309411 TI - Diffuse, perinodular, and other patterns of hydropic degeneration within and adjacent to uterine leiomyomas. Problems in differential diagnosis. AB - We describe 10 uterine leiomyomas with hydropic changes that created problems in differential diagnosis. The patients ranged in age from 41 to 51 years (mean, 45 years). Their presenting symptoms did not differ from those of patients with typical uterine leiomyomas. The follow-up, available for eight patients, was uneventful. Gross and microscopic examination revealed otherwise typical or cellular leiomyomas with focal accumulations of edema fluid (hydropic degeneration), typically associated with variable amounts of collagen ("hyaline degeneration"). Significant accumulations of acid mucins (myxoid degeneration) were present in only one case. These changes resulted in one or more of the following: (a) a characteristic perinodular hydropic change that mimicked intravenous leiomyomatosis on both gross and microscopic examination; (b) hydropic changes extending beyond the confines of the leiomyomas that raised the suspicion of myxoid leiomyosarcoma; and (c) extensive or subtotal obliteration of the usual architecture of the leiomyoma, often accompanied by numerous thick walled blood vessels, that tended to obscure its smooth-muscle nature. Awareness of these changes combined with mucin stains and immunohistochemical stains for endothelial antigens should facilitate the diagnosis. Hydropic leiomyomas are clinically similar to typical leiomyomas; it is obviously important that they not be confused with intravenous leiomyomatosis or myxoid leiomyosarcoma. PMID- 1309412 TI - Pathologic findings in nonpalpable invasive breast cancer. AB - Previous studies have shown that patients with nonpalpable invasive breast cancer have a favorable prognosis. These studies, however, have not analyzed pathologic features of mammographically detected tumors according to tumor size. We describe the histopathologic features of 77 nonpalpable invasive breast cancers, comparing neoplasms less than or equal to 1 cm with larger clinically occult tumors. Forty seven lesions (61%) were less than or equal to 1 cm (group A) and 30 (39%) were greater than 1 cm (group B). In group A, there were 30 infiltrating ductal carcinomas (IDC); seven infiltrating lobular carcinomas (ILC); and two cases each of mixed ILC and IDC, mixed tubular carcinoma and ILC, and infiltrating cribriform carcinoma. There was one case each of mucinous carcinoma, apocrine carcinoma, tubular carcinoma, and mixed mucinous and IDC. In group B, there were 23 (77%) IDC, five (17%) ILC, and two mixed IDC and ILC. Tumors in group B were more frequently grade 3 (22% versus 7%), but this was not statistically significant (p = 0.21). There were no important differences in the frequency, subtypes and location of carcinoma in situ, or other histopathologic parameters evaluated in the biopsy specimens. Mastectomy specimens with axillary lymph node dissections were available for review in 64 cases (83%). Group B patients had a higher rate of residual invasive carcinoma (31% versus 13%) and lymph node metastases (31% versus 16%), but these differences were not statistically significant. Residual carcinoma in situ was more frequent in group B (54%) compared with group A (26%) (p = .036). Of seven group B cases with negative biopsy margins, residual invasive carcinoma was present in five (71%). We conclude that small nonpalpable invasive breast cancers differ from larger nonpalpable tumors primarily in size. The finding of negative biopsy margins should not be construed as conclusive evidence for the absence of residual infiltrating disease. PMID- 1309413 TI - Risk factors for the sexual transmission of genital herpes. AB - OBJECTIVE: To determine the risk of sexual transmission of genital herpes simplex virus (HSV) in heterosexual couples. DESIGN: Prospective study of couples who were participants in a clinical trial. Each source partner had symptomatic, recurrent genital HSV, and each susceptible partner was without serologic or clinical evidence of genital herpes. Couples were followed for a median of 334 days. SETTING: Two university-based research clinics. PATIENTS: One hundred forty four heterosexual couples were studied out of an initial enrollment of 214 couples. MAIN OUTCOME MEASURES: Development of culture-proven HSV infection or type-specific antibodies in the susceptible partner. MAIN RESULTS: Transmission occurred in 14 (9.7%) couples, including 11 (16.9%) of 65 couples with male and 3 (3.8%) of 79 with female source partners (P = 0.05). The annual rate of acquisition was higher (31.8%) in susceptible female partners who lacked antibodies to either HSV type 1 or 2 at entry compared with females with HSV type 1 antibodies at entry (9.1%). Couples avoiding transmission of HSV reported fewer days with genital lesions in source partners. Detailed histories were available at the time of transmission in 13 couples. In nine couples, transmission occurred when the source partner was reported to be asymptomatic and in four, it resulted from sexual contact at the time of prodrome (1 case) or within hours before lesions were first noticed by the source partner (3 cases). CONCLUSIONS: Despite clear recognition of genital herpes in source partners, there was substantial risk for transmission; in 70% of patients, transmission appeared to result from sexual contact during periods of asymptomatic viral shedding. The risk for acquisition of HSV was higher in women than men, and previous HSV type 1 infection appeared to reduce the risk for acquisition of HSV type 2 infection among women. PMID- 1309414 TI - Surgically resected lung cancer in young adults. AB - Twenty-two patients, 40 years old or younger, were surgically treated for lung cancer between 1974 and 1989. The male to female ratio was 1.2:1. Ten patients were symptomatic, with the average duration of symptoms being 3.6 months. There were 13 patients with adenocarcinoma and 9 patients with large cell carcinoma. In terms, of postoperative stages, 5 patients were classified in stage I, 10 in stage IIIa, 5 in stage IIIb, and 2 in stage IV. Complete resection was performed in 14 patients, incomplete resection in 6, and exploratory thoracotomy in 2. The 3-year survival rate after complete resection was 66.2% in young patients, which was not significantly different from the 65.2% 3-year survival rate in older patients. There was no significant difference between the young and older groups according to histological cell type and TNM staging. In cases of incomplete resection or exploratory thoracotomy, 4 of 8 patients had been alive more than 2 years after operation. These results suggest that a long-term survival in the young patients is expected to be almost the same as that in the older patients after either complete resection or incomplete resection. PMID- 1309415 TI - Prognostic significance of massive bronchogenic tumor embolus. AB - Massive arterial bronchogenic tumor embolus is rare, and most commonly occurs intraoperatively during pulmonary resection. Arterial obstruction from the tumor embolus carries substantial morbidity and mortality. For those patients who survive embolectomy, prognosis is most closely correlated with the TNM staging of the primary lung tumor ignoring the tumor embolus. PMID- 1309416 TI - Comparison between resected and irradiated small cell lung cancer in patients in stages I through IIIa. AB - The survival and recurrence of 37 patients with small cell lung cancer who underwent surgical resection were compared with those of 32 patients who were excluded from surgical resection but received radiotherapy. All but 2 patients received chemotherapy. The number of patients in the resected and nonresected groups in each pretreatment clinical stage were, respectively, as follows: 13 and 2 in stage I, 12 and 7 in stage II, and 12 and 23 in stage IIIa. The main reasons for exclusion from surgical resection were locally advanced disease in 15 patients, avoidance of pneumonectomy in 7, and poor pulmonary function in 5. In stage II, the mean tumor size was larger and there were fewer patients with peripheral tumors in the nonresected group than in the resected group. In stage IIIa, there were significantly more patients with overt N2 disease and central tumors in the nonresected group than in the resected group. The 5-year survival rate of the resected group in stage I was 67.7%. Although the nonresected group in stages II and IIIa had many adverse prognostic factors, there was no statistically significant difference between the survival of the resected and the nonresected groups. With respect to the site of first recurrence, a similar pattern was observed in the two groups in each stage, whereas local disease in stage I was completely controlled by surgical resection. These observations suggest that surgical resection can be considered a modality of treatment in clinical stage I. However, the treatment role of surgical resection in clinical stages II and IIIa, even in selected patients, remains unclear. PMID- 1309417 TI - Search for cytomegalovirus in the postmortem brains of schizophrenic patients using the polymerase chain reaction. AB - Cytomegalovirus infection has a number of features that suggest a possible association between congenital infection and schizophrenia. Previous studies have investigated anticytomegalovirus antibody titers or attempted directly to identify viral antigens in body fluids or brain tissue from schizophrenic subjects but have been limited by the sensitivity of the available methods. The highly sensitive polymerase chain reaction, a newly developed technique for gene amplification, was used to search for cytomegalovirus in the DNA extracted from postmortem temporal cortex samples of eight schizophrenic subjects, eight nonschizophrenic suicide victims, and eight normal controls. Cytomegalovirus specific DNA amplification was not detected in any of the samples. The implications of this finding for the viral hypothesis of schizophrenia are discussed. PMID- 1309418 TI - Social skills training for schizophrenia? PMID- 1309419 TI - The H-reflex to magnetic stimulation of lower-limb nerves. AB - We elicited H-reflexes by magnetic and electrical stimulation of several different nerves in 10 healthy subjects and two patients with S-1 radiculopathy. The posterior tibial nerve at the popliteal fossa and the femoral nerve at the inguinal ligament were tested with both electrical and magnetic stimulation; the proximal sciatic nerve was tested only with magnetic stimulation. Muscle activity was recorded from the soleus muscle for posterior tibial and sciatic nerve stimulation and from the vastus medialis muscle for femoral nerve stimulation. No significant difference was found between the latency of H-reflexes evoked by magnetic or electrical stimulation. With magnetic stimulation, the mean (+/- SD) Ia sensory fiber conduction velocity in the proximal segment of the sciatic nerve was 72.4 +/- 3.3 m/s, while the motor nerve fiber conduction velocity in the same portion of the nerve was significantly slower, at 60.6 +/- 2.0 m/s. In two patients with unilateral S-1 radiculopathy, the latency of the H-reflex from the soleus muscle to both magnetic and electrical stimulation of the posterior tibial nerve was absent or prolonged on the affected side. Magnetic stimulation can be used to study the H-reflex and Ia fiber conduction velocity and is particularly advantageous when testing deeply located nerve trunks. PMID- 1309420 TI - Clinical effects of photodynamic therapy on recurrent laryngeal papillomas. AB - Thirty-three patients with moderate to severe recurrent laryngeal papillomatosis underwent photodynamic therapy at our institution. All received 2.5 mg/kg of dihematoporphyrin ether intravenously either 48 or 72 hours prior to photoactivation with an argon pump dye laser system. Photosensitivity was the only side effect seen. Statistical analysis showed a significant decrease, by approximately 50%, in the average rate of laryngeal papilloma growth following treatment. The response was especially pronounced in patients with the worst disease. In addition, three patients have now remained free of disease for extended periods following photodynamic therapy. Latent infection with human papillomavirus continues to persist in clinically normal tissue following photodynamic therapy. The results and potential of this exciting new therapy for laryngeal papillomatosis are described. PMID- 1309421 TI - Platelet-activating factor primes human eosinophil generation of superoxide. AB - Platelet-activating factor (PAF) is a potent inflammatory mediator that can cause airway obstruction and hyperresponsiveness; these processes are also associated with pulmonary eosinophilia, suggesting a link between these two events. Thus, PAF's interaction with eosinophils may provide a mechanism for airway damage. However, direct in vitro activation of eosinophils by PAF requires concentrations that are likely higher than those achieved in vivo. As a result, we investigated whether lower, more physiologic concentrations of PAF could prime eosinophils for subsequent activation to another receptor-stimulated factor, in this case formylmethionylleucylphenylalanine (FMLP). To test this hypothesis, eosinophils were preincubated (1 and 15 min) with low concentrations of PAF (1 x 10(-8) and 1 x 10(-10) M); this exposure to PAF resulted in enhanced generation of superoxide anion to FMLP stimulation. Moreover, similar concentrations of PAF decreased eosinophil density and increased expression of cell surface CR3 receptors. Finally, low, nonactivating concentrations of PAF (1 x 10(-10) to 1 x 10(-8) M) caused transient increases in eosinophil cytosolic free Ca2+ concentrations. Collectively, these responses are consistent with the hypothesis that short-term exposure to low concentrations of PAF primes eosinophils to cause an enhanced inflammatory response upon subsequent activation to another receptor agonist. The consequences of this PAF-associated phenomenon can produce an enhanced inflammatory response and airway injury. PMID- 1309422 TI - Low molecular weight heparin. PMID- 1309423 TI - Endothelium-derived relaxing factor inhibits thrombin-induced platelet aggregation by inhibiting platelet phospholipase C. AB - Endothelium-derived relaxing factor (EDRF) inhibits platelet function, but the mechanism underlying this inhibitory effect is not known. To examine this, cultured acetylsalicylic acid (ASA)-treated endothelial cells (EC) from bovine aorta (BAEC) or from human umbilical vein (HUVEC) were incubated with washed, ASA treated human platelets. Incubation of platelets with either BAEC or HUVEC resulted in inhibition of thrombin-induced platelet aggregation that was dependent on the number of EC added. This effect was potentiated by superoxide dismutase and reversed by treating EC with NG-nitro-L-arginine or by treating platelets with methylene blue, indicating that the inhibition of platelet aggregation was due to the release of EDRF by EC. EC significantly blocked the thrombin stimulated breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and the production of phosphatidic acid in [32P]orthophosphate-labeled platelets and of inositol trisphosphate in [3H]myoinositol-labeled platelets. In addition, the thrombin-mediated activation of protein kinase C (PKC) and phosphorylation of myosin light chain were inhibited in the presence of EC. Finally, thrombin stimulated an increase in cytosolic ionized calcium concentration ([Ca2+]i) in fura2-loaded platelets that was abolished by concentrations of EC which also blocked thrombin-induced aggregation. These data indicate that EDRF blocks thrombin-induced platelet aggregation by inhibiting the activation of PIP2 specific phospholipase C and thereby suppressing the consequent activation of PKC and the mobilization of [Ca2+]i. PMID- 1309424 TI - IgM antibody response in acute hepatitis C viral infection. AB - IgM antibody against hepatitis C virus (IgM anti-HCV) was measured in serial samples from 15 transfusion recipients in whom posttransfusion chronic non-A, non B hepatitis (NANBH) developed and three plasmapheresis donors during acute HCV infection using recombinant proteins derived from three immunodominant regions: core, NS-3, and NS-4 (c100). IgM anti-HCV core was detected in 13 of 15 posttransfusion patients. Nine of these patients had transient, acute-phase IgM anti-HCV core detected coincidentally or earlier than active IgG anti-HCV core response. The average duration of IgM anti-HCV core reactivity was 8.1 +/- 3.7 weeks. One patient lacking an IgM anti-HCV core response had detectable IgM anti HCV NS-3 during the acute phase. Passive transfer of IgM anti-HCV was not observed in these posttransfusion cases, in contrast to the high frequency observed for IgG anti-HCV. Late IgM anti-HCV was detectable against core, c100, and NS-3 in three, two, and one posttransfusion patients, respectively. These data indicate that IgM anti-HCV core is a useful acute-phase marker in HCV infection. PMID- 1309425 TI - Epstein-Barr virus induced lymphoproliferative tumors in severe combined immunodeficient mice are oligoclonal. AB - Severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from Epstein-Barr virus (EBV) negative human donors develop aggressive tumors after the chimeric mice are infected with EBV. The tumors were composed of human B cells that expressed EBV encoded antigens (latent membrane protein and EBV nuclear antigen2). Southern blot analysis of DNA from 16 SCID/hu tumors with human Ig gene probes showed that each tumor contained multiple heavy and light chain gene rearrangements. Ig kappa gene rearrangements were frequent, while clonal lambda gene rearrangements were infrequent. Analysis of EBV terminal repeat sequences indicated two or more fused termini in each tumor, consistent with a multiclonal origin. Linear terminal repeat segments and viral antigens (EA D and EA-R) associated with EBV replication were not detected in the tumors. High levels of human Igs in the SCID/hu serum were oligoclonal and primarily contained kappa light chains. Before the appearance of overt tumors, circulating cells with human and EBV DNA could be detected in the SCID/hu mice by the polymerase chain reaction. We conclude that EBV infection in SCID/hu chimeric mice produces a limited number of transformation events, which give rise to oligoclonal tumors resembling EBV-associated lymphoproliferative disorders in some immune-deficient patients. PMID- 1309426 TI - Synergistic induction of plasminogen activator inhibitor type-1 in HEP G2 cells by thrombin and transforming growth factor-beta. AB - Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. Its activity in plasma increases in diverse thrombotic states. The large synthetic capacity of the liver make it a source of potentially large amounts of PAI-1. Because thrombin activity increases in association with thrombotic disorders and because specific binding sites for thrombin have been identified on hepatocytes, we characterized the effect of thrombin on hepatocyte PAI-1 production. Incubation of Hep G2 cells with human alpha-thrombin resulted in a dose- and time-dependent increase in the concentration of PAI-1 in conditioned media. This effect was inhibited completely by hirudin and by antithrombin III. Steady-state levels of both the 3.2-kb and 2.2-kb forms of PAI 1 mRNA increased after stimulation of the cells with thrombin, indicating that thrombin influences PAI-1 expression in Hep G2 cells at the pretranslational level. Incubation of Hep G2 cells with alpha-thrombin and either platelet lysates or purified transforming growth factor-beta (TGF-beta), both previously shown to augment hepatocyte PAI-1 expression, resulted in a synergistic increase in the concentration of PAI-1 in conditioned media. PAI-1 mRNA appeared to be synergistically increased as well. Thus, thrombin increases expression of both PAI-1 protein and mRNA in Hep G2 cells and exerts synergistic effects with TGF beta. These results underscore the potential importance of inhibition of thrombin under conditions in which thrombolysis is induced pharmacologically. PMID- 1309427 TI - Regulation of glycoprotein IIB/IIIA exposure on platelets stimulated with alpha thrombin. AB - Previous studies have shown that binding sites for fibrinogen on platelets stimulated with platelet-activating factor (PAF), adenosine diphosphate or epinephrine rapidly close in the absence of fibrinogen. In the present study we investigated whether alpha-thrombin induced similar changes in the glycoprotein (GP) IIB/IIIA-complex. Whereas 80% of binding sites exposed by PAF closed within 30 minutes (22 degrees C), alpha-thrombin (0.1 U/mL) triggered long-lasting exposure of binding sites for [125I]-fibrinogen and [125I]-fibronectin. Even removal of alpha-thrombin with an excess of hirudin failed to close the binding sites. Similar to PAF, alpha-thrombin-exposed sites rapidly closed after addition of the protein kinase C inhibitor staurosporine (1 mumol/L) or dibutyryl cyclic adenosine monophosphate (250 mumol/L). In contrast, prostacyclin (PGI2, 10 ng/mL), which induced rapid closure of binding sites in platelets stimulated with PAF, failed to close the sites in alpha-thrombin-treated platelets. Removal of alpha-thrombin from the platelets restored the PGI2-sensitivity. These data indicate that a short interaction between alpha-thrombin and platelets triggers long-lasting exposure of GPIIB/IIIA. Furthermore, as long as alpha-thrombin remains bound to the platelets, agonists that activate the PGI2-receptor are unable to close GPIIB/IIIA. PMID- 1309428 TI - The prevalence of anti-hepatitis C virus among Chinese patients with hepatocellular carcinoma. AB - To evaluate the role of hepatitis C virus (HCV) in Chinese patients with hepatocellular carcinoma (HCC), the antibodies to HCV (anti-HCV) were detected by enzyme immunoassay in 41 (12.6%) of the 326 patients with HCC. However, none of 35 patients with metastatic carcinoma of the liver had detectable anti-HCV. The prevalence of anti-HCV was significantly higher in patients with hepatitis B surface antigen (HBsAg)-negative HCC than those with HBsAg-positive HCC (37.3% versus 4.1%, P less than 0.0001). However, the prevalence of anti-HCV was much higher in patients with HCC with negative results for HBsAg and antibody to hepatitis B core antigen (54.5%). The mean age of patients with HCC with positive results for anti-HCV was significantly greater than that of patients with HBsAg positive HCC (65.1 versus 55.5 years, P less than 0.0001). Alpha-fetoprotein levels greater than 20 ng/ml were found in 70.7% of patients with HCC with positive results for anti-HCV and in 73.3% of patients with HBsAg-positive HCC. Of the Chinese patients with HCC, 74.5% had HBsAg-positive results and 96.6% had positive results for antibody to hepatitis core antigen. These data indicate that, although HCV may play an etiologic role in HCC, hepatitis B virus is still the most important causal agent among most Chinese patients with HCC. PMID- 1309429 TI - Internal radiation therapy for hepatocellular carcinoma. Results of a French multicenter phase II trial of transarterial injection of iodine 131-labeled Lipiodol. AB - Preliminary Phase I trials have shown iodine 131 (131I)-Lipiodol (ethiodized oil; Laboratoires Guerbet, Aulnaysous-Bois, France) to be well tolerated and most likely effective in the treatment of hepatocellular carcinoma (HCC). In this multicenter Phase II trial, the authors tested the feasibility and reproducibility of this treatment in other medical institutions and evaluated its efficacy in 50 patients with unresectable Stage I or II HCC, by the classification of Okuda et al. The authors studied 47 men and 3 women (63.9 +/- 7.1 years old) with Stage I (n = 18) or II (n = 32) HCC, by the classification of Okuda et al., which was verified by histologic findings (n = 25), cytologic findings (n = 11), or association of a tumor with alpha-fetoprotein serum values greater than 500 micrograms/l (n = 14). This multicenter trial (1) confirmed that the 131I-Lipiodol treatment is well tolerated; (2) showed that there is a high reproducibility of results with respect to other institutions and an objective tumor response in 40% of the cases; and (3) indicated the necessity of performing a randomized controlled study. PMID- 1309430 TI - Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction. AB - The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin-fixed, paraffin-embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV-positive and HPV negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV-positive and HPV-negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients. PMID- 1309432 TI - A phase II trial of cisplatin and prolonged administration of oral etoposide in extensive-stage small cell lung cancer. AB - Etoposide is a schedule-dependent agent with greater activity against small cell lung cancer (SCLC) when a given dose is administered over several days compared with a 1-day administration of the same dose. In an attempt to capitalize on the schedule dependency of etoposide, 22 previously untreated extensive-stage SCLC patients were given cisplatin (100 mg/m2 on day 1) plus 21 days of low-dose, oral etoposide (50 mg/m2/d). Chemotherapy was repeated every 28 days for four cycles. Complete blood counts were monitored weekly, and etoposide was discontinued if either the leukocyte or platelet count dropped below 2000/microliters or 75,000/microliters, respectively. All 22 patients were evaluable for response; 18 had either a complete (9%) or partial response (73%), an overall response rate of 82% (95% confidence interval, 62% to 93%). The median response duration was 7 months, and the median survival was 9.9 months (range, 1 to 17+ months). Sixteen (73%) patients received all planned cycles of etoposide. In Cycle 1 of chemotherapy, the median leukocyte nadir was 2700/microliters (range, 100 to 6300/microliters), and median platelet nadir was 180,000/microliters (range, 51,000 to 397,000/microliters). Life-threatening leukopenia (less than 1000/microliters) was rare (3 of 74 cycles). There were three treatment-related deaths, only one of which was associated with neutropenia. One patient had mild renal insufficiency that resolved after discontinuation of therapy. Alopecia was observed in all patients, but other nonhematologic toxicities were uncommon. A randomized study is necessary to determine if this schedule of cisplatin and etoposide administration is superior to more standard methods. However, these data do not indicate a major survival benefit will be derived from increasing the duration of etoposide administration when used in combination with cisplatin given every 28 days. PMID- 1309431 TI - Comparison of outcome between clinically staged, unresected superior sulcus tumors and other stage III non-small cell lung carcinomas treated with radiation therapy alone. AB - Several studies suggest that patients with non-small cell lung carcinoma (NSCLC) of the superior sulcus fare better after radiation therapy than those patients with comparable tumors at other thoracic sites. There is limited data on stage-by stage comparisons between patients with superior sulcus tumors (SST) and non-SST (NSST). Thirty patients had SST among 656 patients with American Joint Committee on Cancer clinically staged IIIA (n = 389) and IIB (n = 267) primary NSCLC who received definitive once-daily radiation therapy. The median patient age, sex ratio, histologic findings, grade, weight loss, and performance status were similar for SST and NSST. Minimum follow-up was 24 months, with 88% of patients followed until death. The survival of patients with SST (median, 10.3 months) was similar to that of patients with tumors at other pulmonary sites (median, 10.8 months; P = 0.39). Survival for favorable patients with performance status 0 to 1 and weight loss of 5% or less was comparable between patients with SST (median, 15.0 months) and NSST were similar for patients with SST and NSST (P = 0.48). The brain was the site of first failure in 20% of patients with SST and 10% of patients with NSCLC at other sites (P = 0.10). The lack of apparent difference in outcome of comparably staged patients with SST and NSST treated with radiation alone may have significant therapeutic implications. PMID- 1309433 TI - Malignant fibrous histiocytoma. A tumor of facultative histiocytes showing mesenchymal differentiation in cultured cell lines. AB - The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologic characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors and immunophagocytosis. However, these cells differed from monocyte-derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu-M1 (CD15) and Leu-M3 (CD14), which recognize the cells of the monocyte-macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes. PMID- 1309434 TI - Increased catechol estrogen metabolism as a risk factor for nonfamilial breast cancer. AB - The metabolism of estrone (E1) or estradiol-17 beta (E2) to catechols seldom has been investigated in biochemical studies related to the risk of development of human breast cancer, as a result of the extreme lability and reactivity of these hormones. A method of indirect calculation was developed in which estimated catechol estrogen excretion (ECE) from urinary excretion of E1, E2, and estriol (E3) was used, based on the obligate reciprocal relation between 16 alpha hydroxylase activity (r3) and estrogen 2/4 hydroxylase function (r2). This relationship is expressed by r2 x r3 = K, the estrogen oxidative constant. From published data relating chiefly to 2-OH estrone excretion, K = 12.4 +/- 0.8 (standard error of the mean). Urinary E1 + E2 excretion rates reflect nonprotein bound plasma ovarian estrogen concentrations available for cell metabolism, which influence the value of K. The equation: r2 = [E1 + E2] K/[E3 + 16 alpha OH E1] = ECE gives a median correlation coefficient between actual catechol estrogen excretion and ECE in micrograms/24 hours of +0.88 (range, 0.61 to 0.97). When tested against the best product isolation analysis of catechol estrogen excretion, ECE was 95% accurate. Using this method a metaanalysis was conducted of published fractional estrogen excretion collected from 2846 healthy women worldwide aged 15 to 59 years, with a risk of breast cancer varying fivefold. Overall ECE was 78% to 97% higher in high-risk women of all ages and menstrual cycle phases (P less than 0.001, by Wilcoxon test). With increasing cancer risk (as estimated by the authors), ECE rose linearly exponentially with a slope of 0.149 (follicular phase) and 0.136 (luteal phase). The correlation coefficient (R2) between the two variables was 0.77 and 0.57, respectively (P less than 0.05). These data derived from calculations of ECE in healthy women confirmed recent analytic results of a twofold increase in the ratio of 2-OH E1/4-OH E1 in healthy Finnish women compared with recent Japanese migrants to Hawaii. In Finnish women with breast cancer, this ratio increased further (almost twofold). Metaanalysis supported the conclusion that increased rates of oxidation of estradiol 17-beta to 2-OH catechols supply the principal proximal human mammary carcinogens active after menarche. PMID- 1309435 TI - Small cell carcinoma of the urinary bladder. A clinicopathologic analysis of 22 cases. AB - Small cell carcinoma of the urinary bladder is an uncommon tumor. The authors report the clinicopathologic findings in a series of 22 cases. Fifteen men and 7 women were studied; their ages ranged from 51 to 87 years (mean, 62.4 years). The most frequent presentation was hematuria (94.4%). At diagnosis, three patients had Stage B disease, six had Stage C, and ten had Stage D (unknown stage in three). Histologically, 6 were oat cell type tumors, 11 were of intermediate cell type, and 5 were of combined cell type. Immunohistochemical studies demonstrated positivity for neuron-specific enolase in ten of ten cases, cytokeratin in seven of ten cases, chromogranin in eight of nine cases, serotonin in seven of nine cases, and S-100 protein in four of ten cases. Neuroendocrine differentiation was seen in five of seven cases examined by electron microscopy. Treatment and follow up data were available for 19 patients: 10 (52.6%) were dead of disease, 5 (26.3%) were alive and well, 3 (15.8%) were alive with disease, and 1 (5.3%) died of an unrelated cause. The 2-year survival rate was 50% for patients with Stage B, 25% for patients with Stage C, and 33% for patients with Stage D disease. Although overall survival was poor, some cases responded well to therapy. Based on the authors' experience, radical cystectomy with adjuvant chemotherapy appears to be the treatment of choice. PMID- 1309436 TI - High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated. AB - Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly. PMID- 1309438 TI - Characterization of platelet-derived growth factor and platelet-derived growth factor receptor expression in asbestos-induced rat mesothelioma. AB - Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor in rodent mesothelioma has not been investigated. In this study, examination of transformed mesothelial cells derived from asbestos induced rat mesotheliomas revealed that these cells expressed high affinity PDGF receptors (Kd = 0.5 nM) and receptor number was 1.6 x 10(5)/cell. Western analysis using antibodies specific for either the alpha-type or beta-type PDGF receptor and Northern analysis using probes specific for alpha- and beta-type receptor RNA transcripts indicated that these cells expressed beta-type PDGF receptors but that alpha-type receptors could not be detected. However, when the mesothelioma-derived cells were examined for the expression of PDGF, no expression of this growth factor could be detected. The transformed cells expressed no detectable A- or B-chain PDGF RNA transcripts; and using a competitive enzyme immunoassay specific for isoforms containing the B chain of PDGF and a sandwich enzyme-linked immunosorbent assay specific for A-chain containing isoforms, neither AA, nor AB, nor BB isoforms of this growth factor could be detected in medium conditioned by these cells. The absence of alterations in PDGF expression in rat mesothelioma, in contrast to the data for the human disease, suggests that the production of this growth factor by transformed mesothelial cells may be species specific. PMID- 1309437 TI - Growth inhibition of transforming growth factor beta on human gastric carcinoma cells: receptor and postreceptor signaling. AB - The effect of transforming growth factor beta (TGF-beta) on human gastric carcinoma cell lines was examined. Cell growth and DNA synthesis of TMK-1 were inhibited by TGF-beta, whereas MKN-28 presented no response to TGF-beta. Scatchard plot analysis of TGF-beta binding showed that TMK-1 had a relatively small number of high-affinity receptors, whereas MKN-28 had a large number of low affinity receptors. By affinity labeling, only the type I receptor (Mr 65,000) for TGF-beta was detected in TMK-1, while three types of receptors, type I, type II (Mr 85,000-95,000), and type III (Mr 250,000-350,000), for TGF-beta were present in MKN-28. TGF-beta treatment reduced p34cdc-2 kinase activity and the level of phosphorylation of retinoblastoma protein in TMK-1, whereas it did not affect them in MKN-28. mRNAs for MYC and platelet-derived growth factor B chain were increased by treatment of TGF-beta on TMK-1. cAMP-responsive element binding activity was decreased by TGF-beta treatment in MKN-28 but not in TMK-1. This was closely correlated with protein kinase C activity. These results suggest that the type I receptor for TGF-beta in human gastric carcinoma cells may be mainly linked with the growth inhibition of TGF-beta by a decrease in retinoblastoma protein phosphorylation by p34cdc-2 without suppression of MYC expression. Conversely, TGF-beta may reduce protein kinase C activity and cAMP-responsive element binding activity in TGF-beta-resistant gastric carcinoma cells. PMID- 1309439 TI - Inhibition of DNA synthesis and growth in human breast stromal cells by bradykinin: evidence for independent roles of B1 and B2 receptors in the respective control of cell growth and phospholipid hydrolysis. AB - The paracrine and intracellular mechanisms controlling stromal cell growth in the normal or neoplastic breast are unknown. This in vitro study uses human breast fibroblasts to investigate a potential role for the inflammatory peptide mediator bradykinin (BK) in the regulation of DNA synthesis and signal transduction in these cells. Bradykinin stimulated a dose-dependent increase in inositol lipid hydrolysis and cytosolic Ca2+ levels in serum-starved fibroblasts derived from both normal and breast tumor tissue. Bradykinin also caused a dose-dependent decrease in cell growth and [3H]thymidine incorporation into DNA in breast fibroblasts. Epidermal growth factor (EGF) and insulin-like growth factor 1 both stimulated DNA synthesis in breast fibroblasts. Bradykinin inhibited this mitogenic effect of EGF but not that due to insulin-like growth factor 1. The binding of 125I-labeled EGF to fibroblasts was also inhibited by BK. Prostaglandin E2 also inhibited fibroblast DNA synthesis, and the cyclooxygenase inhibitor indomethacin partially reversed the inhibitory action of BK on DNA synthesis. Studies with BK receptor antagonists and agonists indicate that inositol lipid signalling and arachidonic acid mobilization in response to BK are B2 receptor-mediated pathways, whereas the inhibition of DNA synthesis appears to be via B1 receptors. Although these data support a role for prostaglandins and EGF receptor down-modulation in the inhibitory action of BK on DNA synthesis in breast fibroblasts, a B1 receptor-mediated pathway is also implicated. This study highlights a potential pathophysiological role for BK as a negative regulator of breast stromal cell growth. PMID- 1309440 TI - Transforming growth factor-alpha acts as an autocrine growth factor in ovarian carcinoma cell lines. AB - The potential of transforming growth factor-alpha (TGF-alpha) to function as an autocrine growth factor was evaluated in numerous ovarian carcinoma cell lines. All 17 lines which were examined expressed the epidermal growth factor receptor and 16 cell lines, in addition, concomitantly secreted TGF-alpha. Radioimmunoassay of processed serum-free-conditioned medium indicated TGF-alpha concentrations ranging from 16 to 197 pg/ml, or 1.5 to 95 ng/10(8) cells. 125I TGF-alpha bound to a single class of high-affinity-binding sites on the surface of the cells. The dissociation constant for the 125I-TGF-alpha/epidermal growth factor receptor complex ranged from 0.21 to 5.3 nM with receptor numbers from 3,500 to 96,000/cell, depending upon the cell line. The growth of 8 ovarian cell lines was stimulated in a dose-dependent manner when grown in the presence of exogenous TGF-alpha. Growth in 4 of 5 cell lines capable of serum-free propagation was inhibited from 28 to 56% when cultured in medium containing a TGF alpha-neutralizing monoclonal antibody. These results support the view that TGF alpha is an autocrine growth factor for cell lines derived from ovarian cancers of epithelial origin and suggest a potential role for TGF-alpha in the pathogenesis or progression of the disease. PMID- 1309441 TI - In vitro apoptosis in the human hepatoma cell line induced by transforming growth factor beta 1. AB - The effect of transforming growth factor beta 1 (TGF-beta 1) on human hepatoma cells (Hep 3B) was studied. Cell death was observed when the serum starved Hep 3B cells were exposed to a very low concentration of TGF-beta 1. The half-maximal cytocidal concentration of TGF-beta 1 was around 20 pM. Cell death began approximately 24 h following treatment, with more than 80% of the cells dying after 48 h. In contrast, the control cells, which were cultured in serum-free condition, still gradually proliferated. Furthermore, the cytocidal effect of TGF beta 1 on Hep 3B cells was not altered by either cycloheximide or actinomycin D. It was discovered, using diphenylamine assay, that TGF-beta 1 induced DNA fragmentation in Hep 3B cells. Using gel electrophoresis, the fragmented DNA could be displayed, and showed a characteristic stepladder pattern. Thus, it appeared that TGF-beta 1 induced a particular pathway in Hep 3B cells in which de novo protein synthesis was not actively involved, but endogenous nuclease was activated which cleaves cellular DNA and induces cell death. PMID- 1309442 TI - Anticancer effects of free polyunsaturated fatty acids in an oily lymphographic agent following intrahepatic arterial administration to a rabbit bearing VX-2 tumor. AB - The anti-hepatic cancer effects of three free polyunsaturated fatty acids (linoleic, alpha-linolenic, and gamma-linolenic acids) dissolved in an oily lymphographic agent, Lipiodol Ultra-Fluid (Lipiodol), following intrahepatic arterial administration were examined using a rabbit liver cancer model, VX-2. The tumor was inoculated into the subcapsular parenchyma of the liver of rabbits, and Lipiodol alone or Lipiodol containing each one of the free fatty acids was administered into the hepatic artery 14 days after inoculation. The rabbits were sacrificed 7 days after administration. Lipiodol containing one of the fatty acids selectively remained in the tumor area. Although VX-2 tumor grew extensively in both the untreated group and the group that received Lipiodol alone, growth of VX-2 tumor was greatly suppressed in the group that received Lipiodol containing the free fatty acid. Pathological observation also showed that Lipiodol containing the free fatty acid had an anticancer effect on VX-2 tumor growing in the liver of rabbits. Average survival days in the group treated with Lipiodol containing gamma-linolenic acid were significantly prolonged compared with those in the control groups. Although growth rates of the tumor at the death of rabbits were large in the control groups, VX-2 tumor shrank at death of five rabbits of six in the group treated with Lipiodol containing gamma linolenic acid. These results suggest that the intrahepatic arterial administration of Lipiodol containing the free fatty acids is an effective method of delivery of these fatty acids as anticancer agents. PMID- 1309443 TI - Classification of antiarrhythmic agents: electropharmacologic basis and clinical relevance. AB - Only antiarrhythmic agents with class I activity prolong QRS duration The most marked QRS prolongation is produced by the IC agents, followed by IA and IB. This is consistent with the kinetics of interaction of each of these three subclasses with the sodium channel. Amiodarone's effect on QRS duration is between that of the IB and IA agents consistent with its tau rec of 1.5 seconds. Moricizine's effects on QRS duration are more marked than would be expected from its tau rec of 2.6 seconds but may be explained by the slow onset of inactivation block. The greatest efficacy in VPC suppression is exhibited by the class IC agents and amiodarone. Although amiodarone and sotalol are included in class III, amiodarone has marked class IB activity and sotalol is a more potent beta-adrenergic blocker. The disparate effects of these two drugs in suppressing VPCs may be explained by the class I action of amiodarone. It is surprising that drugs within each subclass correlate at all in VPC suppression in view of the marked heterogeneity of mechanisms potentially producing VPCs. Antiarrhythmic agents with class III activity seem to be the most effective in patients with inducible sustained ventricular tachyarrhythmias. Except for the class I agents with class III activity, that is, IA agents, all class I agents are effective in only 10% to 15% of patients with inducible ventricular tachycardia. The discordance between sotalol and amiodarone is unexplained. As expected, the most marked prolongation of ventricular tachycardia cycle length occurs with the class IC agents, followed by class IA and IB. At the rapid rates of the ventricular tachycardia, frequency dependent sodium channel block occurs even with the "fast IB" drugs, and ventricular tachycardia cycle length is prolonged. PMID- 1309444 TI - Increased urinary leukotriene excretion in patients with cardiac ischemia. In vivo evidence for 5-lipoxygenase activation. AB - BACKGROUND: Experimental cardiac ischemia in some animal models results in the activation of the enzyme 5-lipoxygenase and the subsequent production of leukotrienes, potent proinflammatory lipid mediators, by the affected myocardium. Furthermore, prototype antileukotriene drugs can show some beneficial effects on infarct size and cardiac function in these models. Accordingly, urinary excretion of leukotriene E4 (LTE4), the major urinary metabolite of peptide leukotrienes in humans, was measured in patients admitted to the hospital with evidence of acute myocardial ischemia to assess in vivo release of 5-lipoxygenase products during and after the ischemic episode. METHODS AND RESULTS: Urinary leukotriene excretion was measured by reversed-phase high-performance liquid chromatography and specific radioimmunoassay on admission with acute chest pain and again on day 3 in the following patient groups: acute myocardial infarction (AMI), AMI and clinical evidence of early reperfusion after treatment with recombinant tissue type plasminogen activator (rt-PA), diagnosis of unstable angina (UA) based on clinical history and coronary arteriography, controls with nonischemic chest pain who underwent coronary arteriography, and age-matched controls and normal hospital employees. In 16 patients with diagnosis of AMI, LTE4 excretion on admission (331 +/- 99 pg/mg creatinine sulfate; mean +/- SEM) was considerably higher than that measured on day 3 (195 +/- 59 pg/mg creatinine sulfate). In a subgroup of seven subjects treated with rt-PA resulting in early reperfusion, day 1 excretion was similar (215 +/- 50 pg/mg) but had significantly declined by day 3 (65 +/- 16 pg/mg; p less than 0.01). Urinary LTE4 excretion at admission for chest pain was also elevated in 14 patients having unstable angina (UA; 370 +/- 125 pg LTE4/mg creatinine sulfate). This had declined significantly (p less than 0.05) by day 3 (at which time chest pain had resolved) to 94 +/- 31 pg/mg creatinine sulfate, an excretion rate comparable with that measured in eight similarly aged subjects (64 +/- 12 pg/mg creatinine). CONCLUSIONS: This study suggests that peptide leukotrienes are released during episodes of myocardial ischemia and provides clinical evidence for involvement of their biosynthetic enzyme, 5-lipoxygenase, during and after acute myocardial infarction and unstable angina attacks. Thus, potent and specific orally active leukotriene biosynthesis inhibitors may have therapeutic potential in limiting myocardial damage and functional abnormalities after acute ischemia. PMID- 1309445 TI - Myocardial beta-adrenergic receptor expression and signal transduction after chronic volume-overload hypertrophy and circulatory congestion. AB - BACKGROUND: The volume-overload, high-output state induced by aortocaval fistula is unique because it is not generally associated with marked abnormalities of contractile function. Thus, changes in beta-adrenergic receptor (beta AR) expression should reflect more directly the influence of neurohumoral adrenergic tone, clarifying the manner in which peripheral (neurohumoral) versus primary myocardial factors are operative in decreased beta AR-dependent signal transduction. METHODS AND RESULTS: We examined the beta-adrenergic receptor responsive adenylyl cyclase pathway in hearts from pigs subjected to volume overload hypertrophy with circulatory congestion. Nine pigs underwent initial pharmacological and hemodynamic studies, and, 5 weeks after aortocaval fistula placement, when signs of circulatory congestion were evident, these measurements were repeated. Biochemical analyses of plasma and myocardium from these animals and seven normal animals were compared. Experimental animals showed signs of circulatory congestion (tachypnea, weight gain, pulmonary rales) within 3-4 weeks of fistula placement. Necropsy showed ascites and biventricular cardiac hypertrophy, but no fibrosis or inflammation was present on histological inspection. Heart rate responsiveness to beta AR stimulation was blunted, with ED50, for isoproterenol increased 133% (p less than 0.001) after development of circulatory congestion. Biochemical analyses of the beta AR-responsive adenylyl cyclase pathway showed uniform decreases in beta AR number in right atrium, right ventricle, and left ventricle (36-41% decreases, p less than 0.005). Downregulation was selective for beta 1-receptors, and remaining receptors in the right and left ventricles showed low-affinity agonist binding, suggesting an uncoupling from Gs. All measures of adenylyl cyclase activity were diminished significantly in membrane homogenates from the right atrium (mean reduction, 50 +/- 10%) and left ventricle (mean reduction, 44 +/- 8%) after volume overload. Finally, we found that amounts of cardiac Gs, as measured in reconstitution assays, were decreased in both the right atrium (p less than 0.02) and the left ventricle (p less than 0.01) of volume-overloaded animals but that levels of pertussis toxin substrate were unchanged. CONCLUSIONS: Biochemical findings occurred in the absence of myocardial inflammation or fibrosis and without pharmacological interventions, suggesting that circulatory congestion, with attendant elevation in plasma norepinephrine, may be a sufficient stimulus to induce such changes. The data are compatible with a catecholamine-driven beta AR pathway desensitization. Thus, a primary defect in intrinsic contractile function is not a necessary component for abnormalities of the myocardial beta AR responsive adenylyl cyclase pathway. PMID- 1309446 TI - Renin system inhibition. Beginning the fourth epoch. PMID- 1309447 TI - Myocardial catecholamine and neuropeptide Y depletion in failing ventricles of patients with idiopathic dilated cardiomyopathy. Correlation with beta-adrenergic receptor downregulation. AB - BACKGROUND: Myocardial adrenergic neurotransmitters and beta-adrenergic receptor levels were measured in left and right ventricular myocardial specimens obtained from 30 patients with biventricular failure resulting from idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Nonfailing myocardium obtained from 12 organ donors provided control data. Norepinephrine, dopamine, and neuropeptide Y concentrations were significantly decreased in failing compared with nonfailing control hearts. The mean ratio of dopamine to norepinephrine and of dopamine to neuropeptide Y in failing hearts was also significantly decreased compared with nonfailing control hearts. Compared with nonfailing control hearts, Bmax and beta 1-receptor density were significantly decreased in failing hearts and there were weak but significantly positive correlations of Bmax and beta 1-adrenergic receptors with norepinephrine, dopamine, and neuropeptide Y. CONCLUSIONS: Norepinephrine and its cotransmitter neuropeptide Y are depleted in failing human ventricular myocardium. Decreased norepinephrine stores correlate weakly with beta 1-adrenergic receptor downregulation consistent with the hypothesis that norepinephrine depletion occurs in response to increased adrenergic drive. Decreased dopamine relative to norepinephrine implies that an abnormality of dopamine conversion to norepinephrine is not present in failing human heart. PMID- 1309449 TI - Prevalence of anti-hepatitis C virus antibodies among patients with alcoholic liver disease, supplemented by 4-RIBA. PMID- 1309448 TI - Hepatitis B virus. New and evolving issues. AB - Recent developments in molecular biology have advanced our understanding of the pathogenesis of HBV-induced disease. New data derived from the molecular analysis of clinical material have begun to bridge the gap between bench research and the clinical arena. In this review, we consider topics that have relevance to clinical management and that have not been summarized in the recent literature. The recent advances that have been made in the areas of HBV variants, in vitro cell culture systems, and extrahepatic infection are discussed in greater detail. PMID- 1309450 TI - Hepatitis B virus markers and antibodies to hepatitis C virus in Japanese patients with hepatocellular carcinoma. AB - Sera from Japanese patients with chronic liver disease were tested for hepatitis B virus (HBV) markers and antibodies to hepatitis C virus (anti-HCV), and the results were correlated to the presence of hepatocellular carcinoma. In chronic non-A, non-B liver disease, anti-HCV prevalence was high both in patients with hepatocellular carcinoma (78/89, 88%) and without it (66/84, 79%), while previous HBV infection was more common in patients with hepatocellular carcinoma (65/89, 73%) than in those without it (46/84, 55%) (P less than 0.05). Coexistence of anti-HCV and antibodies to HBV was observed frequently in patients with hepatocellular carcinoma (56/89, 63%) compared with patients without it (39/84, 46%) (P less than 0.05). In chronic HBV carriers, anti-HCV was more common in patients with hepatocellular carcinoma (12/38, 32%) than in those without it (3/62, 5%) (P less than 0.01). These results suggest that infection with the two viruses may be a risk factor for more serious liver disease. PMID- 1309452 TI - Mild adrenal 3 beta-hydroxysteroid dehydrogenase deficiency in children with accelerated growth, premature pubarche and/or hirsutism. AB - We studied eight children (seven girls and one boy, of whom three are siblings) with accelerated growth, premature pubarche and/or hirsutism between the ages of 7 and 9.5 years. These patients were studied for the presence of adrenal steroidogenic defect by adrenocortico tropic hormone (ACTH) stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Baseline and stimulated 17 hydroxypregnenolone (delta 5-17P), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), androstenedione (delta 4-A), testosterone, and cortisol levels were measured. Six children, including three siblings, were diagnosed with a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency based upon the elevated response of serum delta 5-17P and the elevated ratio of delta 5-17P/17-OHP and of DHEA/delta 4-A to ACTH stimulation. Thus, a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency may not be uncommon in children with accelerated growth, premature pubarche and/or hirsutism and routine assay of delta 5-steroid metabolites should be generally available. PMID- 1309453 TI - Nerve growth factor receptor and the transplanted rat olfactory bulb. AB - Nerve growth factor receptor (NGFR) in the rat olfactory system is developmentally regulated, localizing to the olfactory nerve (ON) in the young rat, and to the olfactory bulb (OB) glomeruli in the adult (Vickland et al. 1991. Brain Res., in press). This pattern of immunoreactivity (IR) may indicate the state of axon growth in the young ON and synaptogenesis in the adult glomeruli. Additional experiments in our laboratory involving lesions to the ON in adult rats have shown a recapitulation of the developmental pattern of expression: NGFR IR is again found along the ON. Longer survival times after lesioning show the reexpression of the adult pattern of NGFR-IR. This phenomenon was further explored in a transplant (TX) model to determine the changes in NGFR-IR in both the host and TX tissue. A fetal OB labeled with [3H]thymidine is placed into the space created by the removal of the OB of a neonatal rat. After survival times of 1, 2, 8, and 13 weeks, the host animal is sacrificed and the OB TX is processed using monoclonal antibody 192 IgG for NGFR. The host ON shows strong NGFR-IR in TX of 1- and 2-week survival times. In TX survival times of 8 weeks or more, NGFR IR is observed in glomerulus-like structures. All of these glomerulus-like structures are near groups of neurons in the TX tissue, indicating that they may be functional, with appropriate synapses. Therefore, even though the adult pattern of NGFR-IR takes longer to become established than in normal rats, we have demonstrated that this pattern does so in the TX OB model. PMID- 1309451 TI - Growth-regulatory effects of glucagon, insulin, and epidermal growth factor in cultured hepatocytes. Temporal aspects and evidence for bidirectional control by cyclic AMP. AB - Data presented indicate that in hepatocytes insulin and glucagon promote growth by acting in a relatively early part of the prereplicative period (G0 or early G1) whereas cells (if pretreated with insulin) become more sensitive to EGF at the later stages, ie, nearer the S phase entry. The data indicate that at least two effects of glucagon (cAMP) on hepatocyte proliferation exist; in addition to a growth-promoting modulation early in the prereplicative period, there is also an inhibitory effect of glucagon (as well as other cAMP-elevating agents) that is exerted at a point shortly before the G1-to-S transition. Because both effects occur dose-dependently in the normal range of glucagon concentrations in portal blood, it is conceivable that glucagon/cAMP is involved both when liver growth is initiated and terminated. PMID- 1309454 TI - Vibrissaeless mutant rats with a modular representation of innervated sinus hair follicles in the cerebral cortex. AB - Specialized areas in the cerebral cortex are essential to mediate the various sensory modalities and are crucial to their recovery in disease. We recently observed that prenatal photoreceptor cues are not indispensable for the development of the elaborate modular organization of the primate primary visual (striate) cortex (Kuljis, R. O. and P. Rakic. 1990. Proc. Natl. Acad. Sci. USA 87: 5303-5306). By contrast, the elegant experiments of Woolsey, Van der Loos, and collaborators (Van der Loos, H., and T. A. Woolsey. 1973. Science 179: 395 398; Van der Loos, H. and J. Dorfl. 1978. Neurosci Lett. 7: 23-30; Woolsey, T. A. 1967. John Hopkins Med. J. 121: 91-112; Woolsey, T. A. and H. Van der Loos. 1970. Brain Res. 17: 205-242) indicate that postnatal vibrissal receptor input is necessary for the development of modular organization in the posteromedial barrel subfield (PMBSF) of the rodent somatosensory cortex. The present report is part of a series of studies designed to address the variables that result in seemingly different results in these two models. Here, I address the role of pre- and postnatal tactile experience in the development of the rat homologue of the mouse PMBSF using mutants that lack vibrissae. Mutants exhibit cytoarchitectonic units in layer IV similar to those in controls, as revealed by NissI stains and histochemistry for succinate dehydrogenase and cytochrome oxidase. Sections from flat mounts of the vibrissal pad reveal that all mutants contain vibrissal follicles with stumps of sinus hairs in a geometric array and number similar to that in controls, and that the follicles are innervated heavily by fascicles of fibers from the infraorbital nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309455 TI - Immunolocalization of basic fibroblast growth factor and its receptor in adult goldfish retina. AB - The neural retina of teleost fish can regenerate following surgical or neurotoxic lesions. As a first attempt to uncover the factors important for the regenerative response, we used immunocytochemistry to demonstrate the presence of basic fibroblast growth factor (bFGF) and its receptor in the goldfish retina. The bFGF immunoreactivity was present throughout the retina, but was most intense in photoreceptor cells, especially cones, and Muller glia. Immunoreactivity for the bFGF receptor was strongest in the axon terminals of photoreceptors, both rods and cones. This pattern of immunolocalization is especially interesting since the proliferating cells that are thought to be responsible for generating the neural regenerate are located among the photoreceptor axon terminals. These proliferating cells have been identified as rod precursors because in the intact retina they give rise only to rod photoreceptors. When the neural retina is damaged, however, rod precursors are thought to be the source of proliferating neuroepithelial cells responsible for generating the retinal regenerate. The role played by bFGF in normal neurogenesis, cell differentiation, and/or neuronal regeneration in the fish retina has yet to be determined. PMID- 1309456 TI - Activation of polyphosphoinositide metabolism at artificial maturation of Patella vulgata oocytes. AB - The metabolism of polyphosphoinositides (PPI) has been investigated during the meiosis reinitiation of the oocytes of a prosobranch mollusk, the limpet Patella vulgata. Meiosis reinitiation which leads to germinal vesicle breakdown (GVBD) and metaphase-1 spindle formation was artificially induced by treating the prophase-blocked oocytes with 10 mM NH4Cl, pH 8.2. This treatment, which results in a rise in intracellular pH, triggered a general increase in polyphosphoinositide synthesis. Determinations of phosphorus content showed that maturation induced a 30 to 50% increase in both phosphatidylinositol (PI) and phosphatidylinositol-1 monophosphate (PIP) concentrations. Incorporations of 32PO4 and [3H]inositol have been measured in three classes of polyphosphoinositides: PI, PIP, and phosphatidylinositol 4,5-bisphosphate (PIP2). By comparing incorporation rates of the radiolabeled precursors into PPI before and after meiosis reinitiation, we found that artificial maturation by ammonia induced a 50-fold increase in the turnover of these lipids. No significant burst of inositol 1,4,5-trisphosphate (IP3) was observed after maturation. We suggest that modifications in PPI metabolism occurring at maturation of Patella oocytes might ensure the formation of an important stock of PPI that would be available for the profuse production of IP3, the messenger responsible for the Ca2+ signal at fertilization. PMID- 1309457 TI - Cell-type-specific responsiveness to cAMP in cell differentiation of Dictyostelium discoideum. AB - In Dictyostelium discoideum, both prespore and prestalk differentiation require extracellular cAMP. We investigated the difference in inducibility of the two cell types by cAMP. Previous studies indicate that cAMP added in the early stage of development inhibits prespore differentiation, and this was confirmed using three species of prespore specific mRNAs. By contrast, early treatment with cAMP did not inhibit, but induced the expression of prestalk-specific mRNA. These results indicate that differentiation pathways of the two cell types have different processes in the early stage of development. PMID- 1309458 TI - Muscle-derived agrin in cultured myotubes: expression in the basal lamina and at induced acetylcholine receptor clusters. AB - The synaptic basal lamina (SBL) directs key aspects of the differentiation of regenerating neuromuscular junctions. A range of experiments indicate that agrin or a closely related molecule is stably associated with the SBL and participates in inducing the formation of the postsynaptic apparatus after damage to adult muscle. The selective concentration of agrin-related molecules in the SBL suggests that agrin is secreted locally by cellular components of the nerve muscle synapse. In vivo studies on aneural embryonic muscle indicate that the muscle cell is one source of the agrin-like molecules in the SBL. Here we have used cultured chick muscle cells to study the expression of agrin-related molecules in the absence of innervation. Immunofluorescence and immunoelectron microscopy show that myogenic cells in culture express agrin-related molecules on their surfaces, and that at least a subset of these molecules are associated with the basal lamina. Moreover, in short term cultures agrin-like molecules accumulate on the surfaces of myogenic cells grown in unsupplemented basal media. We quantified the expression of agrin-like molecules on the cell surface using a solid-phase radioimmune assay. The expression of these molecules is relatively low during the first 6 days of culture and increases fourfold during the second week. The stimulation of the expression of agrin-related molecules in these long term cultures requires the presence of chick embryo extract or fetal calf serum. We also characterized the expression of muscle-derived agrin-like molecules at clusters of AChR. These agrin-related molecules are not consistently colocalized at spontaneous AChR aggregates; however, they are selectively concentrated at greater than or equal to 90% of the AChR clusters that are induced by Torpedo agrin. These data, together with previous results from in vivo developmental experiments indicate that the agrin-like molecules in the synaptic basal lamina are derived at least in part from the muscle cell. In addition, the expression of agrin-like molecules can be regulated by soluble factors present in CEE and FBS. Finally, the selective localization of these molecules at induced AChR clusters, taken together with their localization in the basal lamina, suggests that agrin like molecules secreted by the muscle cell play an important role in the formation and/or the stabilization of the postsynaptic apparatus. PMID- 1309459 TI - Genital papillomavirus infection and cervical dysplasia--opportunistic complications of HIV infection. AB - Certain human genital papillomaviruses (HPV) are strongly associated with cervical dysplasia and cancer. Evidence is accumulating that HPV infection and ano-genital cancers are more common in patients with the acquired immunodeficiency syndrome. The objective of our study was to evaluate the extent to which HPV infection and associated cervical disease constitute opportunistic complications of human immunodeficiency virus (HIV) infection in a population of sexually promiscuous, HIV-infected women in Kinshasa, Zaire. In 1989 we obtained Pap smears and cervicovaginal lavage specimens for HPV DNA testing from 47 HIV seropositive and 48 HIV-seronegative prostitutes who were part of a cohort under observation since 1988. Thirty-eight percent of the HIV-seropositive and 8% of the seronegative women (odds ratio = 6.8; p = 0.001) had HPV DNA detected by either ViraType, a dot-blot assay which detects specific genital HPV types, or low-stringency Southern blot, which detects all HPV types. Eighty-two women (86%) had an interpretable Pap smear; 11 of 41 (27%) HIV-seropositive women and one of 41 (3%) seronegative women had cervical intra-epithelial neoplasia (CIN) (odds ratio = 14.7; p = 0.002). HIV seropositivity, HPV infection and CIN were highly associated. Eight (73%) of 11 seropositive women with CIN had HPV detected. Both HPV infection and cervical cancer may emerge as opportunistic complications of HIV infection in populations in which HIV, HPV and cervical cancer are common. PMID- 1309460 TI - Tumor-antigen-specific humoral immune response of animals to anti-idiotypic antibodies and comparative serological analysis of patients with small-cell lung carcinoma. AB - We have previously developed 3 monoclonal anti-idiotypic antibodies (Ab2) of LOU rat origin directed against the binding site of the murine monoclonal IgM LAM8, which recognizes the small-cell lung carcinoma (SCLC)-associated sialoglycoprotein antigen sGP 90-135. The aim of this study was to compare the efficiencies of these 3 Ab2, designated LY8-229, LX8-531 and LX8-632, to induce antigen-specific immunity in different animal species without prior exposure of the recipients to the nominal antigen, and thereby possibly select an Ab2 candidate for active immunotherapy against SCLC in patients. The feasibility of this approach was further evaluated by a serological analysis of patients with SCLC compared with healthy individuals, in whom the spontaneous antibody reactivities against SCLC cell lines and Ab2 were tested. LY8-229 was shown to be the most effective Ab2 in inducing antigen-specific antibodies in BALB/c mice, CBA/J/Zur mice and one NZW rabbit. Furthermore, LY8-229 was the only Ab2 against which significantly elevated idiotype-specific antibody reactivities existed in sera of patients with SCLC. These reactivities correlated positively with binding to antigen-positive tumor cells. Our findings suggest that LY8-229 represents in its reactivity pattern the nominal SCLC antigen in humans also, and therefore may be of diagnostic and possibly therapeutic relevance for patients with SCLC. PMID- 1309461 TI - Leukotriene B4-induced human melanocyte pigmentation and leukotriene C4-induced human melanocyte growth are inhibited by different isoquinolinesulfonamides. AB - Leukotriene C4 (LTC4) is known to be a potent mitogen for cultured human neonatal melanocytes. We now demonstrate that leukotriene B4 (LTB4) can induce pigmentation in cultured human neonatal melanocytes in a dose-dependent fashion. The LTC4-induced mitogenesis is blocked by the cyclic nucleotide-dependent kinase inhibitor N-[2-(methyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8). The LTB4-induced pigmentation is blocked by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7). We propose that LTB4-induced pigmentation and LTC4-induced mitogenesis are important in vivo signals. Their different effects in our culture system are blocked by different protein kinase inhibitors. PMID- 1309462 TI - Detection of viral DNA within skin of healed recurrent herpes simplex infection and erythema multiforme lesions. AB - The polymerase chain reaction (PCR) was used to detect HSV DNA in genomic DNA extracted from skin biopsies obtained from healed skin of five patients with hyperpigmented macules following recurrent cutaneous HSV infections and from eight patients with HSV-associated erythema multiforme (EM). A 92-bp HSV-1 DNA fragment was found in all the skin biopsies from the site of recurrent HSV infection and in five of eight (62%) biopsies from the EM patients. Virus DNA was not found in tissues distant from the site of HSV recurrence or from a patient without a history of HSV infection. These findings confirm the presence of HSV in healed skin from the site of recurrent HSV disease and are consistent with the concept that HSV is involved in EM pathogenesis. PMID- 1309463 TI - Colposcopy in a family practice residency. The first 200 cases. AB - BACKGROUND: The incidence of abnormal Papanicolaou smears has increased dramatically in the last decade. Many family physicians now find it necessary to perform colposcopies themselves to provide optimal care for their patients. There is little literature that evaluates the performance of this procedure by family physicians. METHODS: The findings of the first 200 colposcopies performed in a community hospital-based family practice residency program are reported. Descriptive data were prospectively gathered between August 1987 and December 1989. RESULTS: The median age of the patients was 25 years, the median number of sexual partners was three, and the median age at the time of first sexual intercourse was 17 years. The majority had colposcopy performed because of a class III Papanicolaou smear (108 [54%]). Twenty-five (12.5%) were pregnant at the time of colposcopy; for this reason a biopsy was not performed on 19 of the patients. An average of three distinct cervical lesions were seen in each patient. The most frequent histologic finding was some degree of dysplasia (116 of 181 biopsied [64%]). Twenty-two cases of severe dysplasia (carcinoma in situ) were found. However, no cases of invasive carcinoma were found. CONCLUSIONS: High quality colposcopy and effective treatment with appropriate referral can be done at the primary care level for most patients. Many patients failed to return for follow-up evaluation after treatment, indicating the need for better tracking of patients. PMID- 1309464 TI - Influence of mineral dust surface chemistry on eicosanoid production by the alveolar macrophage. AB - It has been suggested that radicals on the surface of dust particles are key chemical factors in the pathophysiology that results from the occupational inhalation of coal and silica dust. In addition, oxygenated derivatives of arachidonic acid (eicosanoids) have been implicated as important biochemical mediators of mineral dust-induced lung disease through their role in bronchial and vascular smooth muscle reactivity, inflammation, and fibrosis. Therefore, we assessed eicosanoid production by the rat alveolar macrophage (AM) exposed in vitro to mineral dusts with varying surface chemical characteristics in order to determine if radicals associated with the mineral dust could influence the production of proinflammatory mediators in the lung environment. Primary cultures of rat AM were exposed to freshly fractured or "stale" bituminous coal dust, as well as untreated silica or silica calcined to 500 and 1100 degrees C. Prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and leukotriene B4 (LTB4) levels in incubation medium were determined by specific radioimmunoassay. When AM were exposed to freshly fractured coal dust, PGE2 production was markedly increased. In contrast, exposure of AM to "stale" dust significantly reduced PGE2 production. Exposure of AM to freshly fractured coal dust resulted in a significant increase in production by AM, while exposure to stale coal dust did not influence AM TXA2 production. Neither "fresh" nor "stale" coal dust had any effect on LTB4 production. In vitro exposure of AM to untreated silica resulted in a significant increase in TXA2 PGE2, TXA2, and LTB4 production compared with control. However, exposure of AM to silica calcined to 1100 degrees C resulted in eicosanoid levels that were not significantly different from control. These effects were still apparent 8 wk after calcination of the silica particles. Silica was a more potent activator of AM eicosanoid production than was coal, and amorphous fumed silica was a more potent activator of AM eicosanoid production than was crystalline silica. These findings suggest that radicals associated with respirable coal and silica particles may play a key role in the ability of mineral dust to activate AM eicosanoid production and therefore may be important in the pathophysiological consequences of occupational mineral dust inhalation. PMID- 1309465 TI - Enzymatic harvesting of adult human saphenous vein endothelial cells: use of a chemically defined combination of two purified enzymes to attain viable cell yields equal to those attained by crude bacterial collagenase preparations. AB - Seeding vascular prostheses with enzymatically harvested endothelial cells can create endothelial linings that improve small-caliber prosthetic patency. But crude bacterial collagenases used for endothelial harvest contain cytotoxic nonspecific proteases and clostridial cell wall debris which might limit their clinical usefulness. We therefore compared the endothelial cell harvest efficiency of crude bacterial collagenase with that of purified bacterial collagenase alone, purified trypsin alone, and combinations of purified bacterial collagenase and trypsin using concentrations of pure collagenase equal in collagenolytic activity to the crude bacterial collagenase material. The efficiency of harvest from human saphenous vein segments was measured by a microtiter well-growth curve assay of the number of living endothelial cells capable of attachment to fibronectin and subsequent growth obtained per unit area of saphenous vein lumen. Whereas pure collagenase and purified trypsin alone both harvested less than 5% of the baseline endothelial cell density on the veins, a combination of purified collagenase and 0.01% w/v purified trypsin was found to harvest 22% +/- 10% (SD) (n = 8 veins) of the approximately 1.3 x 10(5) endothelial cells/cm2 available on normal saphenous veins. This figure was not statistically different from the harvest efficiency of 19% +/- 10% (N = 4 veins) (p greater than 0.05) obtained by use of 0.1% w/v crude collagenase alone. This result suggests that endothelial harvesting can be done with a defined mixture of pure enzymes which would be clinically preferable to presently used crude extracts of clostridial cultures as a standardized preparation for graft seeding. PMID- 1309466 TI - Single lung transplantation. Factors in postoperative cytomegalovirus infection. AB - Thirty-one single lung transplantations were performed between March 17, 1988, and November 1, 1990. Postoperative infection, especially with cytomegalovirus, has been the major cause of morbidity and mortality. Eighteen of the 31 patients were receiving prednisone before transplantation. Every patient was prepared preoperatively with oral cyclosporine 5 mg/kg and azathioprine (Imuran) 2 mg/kg. Every patient received methylprednisolone for 3 days postoperatively, followed by prednisone 1.0 mg/kg/day, oral cyclosporine, and azathioprine. Ten patients additionally had cytolytic therapy with OKT3 and 12 with antilymphocyte globulin. Nine patients had no cytolytic therapy. Cytolytic therapy was chronologic, not randomized. Postoperative infection occurred in 20 patients, 13 of whom had cytomegalovirus infection. Preoperative use of prednisone did not correlate with postoperative infection, cytomegalovirus, or death. Postoperative infection occurred in 17 of 22 patients with cytolytic therapy compared with three of nine without cytolytic therapy (p = 0.035). Cytomegalovirus infection occurred in 13 of 22 with cytolytic therapy and in none of the nine without cytolytic agents (p = 0.003). Therefore preoperative prednisone does not appear to be a contraindication to single lung transplantation. Cytolytic therapy with either OKT3 or antilymphocyte globulin increases the prevalence of postoperative infection with cytomegalovirus and should not be used in patients undergoing lung transplantation. PMID- 1309467 TI - Surgery and the management of peripheral lung tumors adherent to the parietal pleura. AB - Among 37 patients with peripheral T3 lung lesions, preoperative clinical and imaging evidence was suggestive of T3 disease in 28 and of T2 disease in nine. Intraoperatively, the T2 designation was changed to T3 on the basis of adherence of the tumor to the parietal pleura. All had mediastinoscopy followed by resection and complete lymph node dissection. There were 17 lobectomies and 20 pneumonectomies. The chest wall was resected in continuity with the lung in 21 patients, and in 16 only an extrapleural resection was done. Follow-up was completed in all patients (range 2 to 14 years, median 7 years). The 5-year actuarial survival rate for all patients was 30%. As expected, the presence of lymph node metastasis affected the 5-year actuarial survival rate: N0 = 41%; N1 = 29%, and N2 = 0%. Histologic examination of the resected specimen confirmed a T3 lesion in 30 patients. The tumor was removed completely in 100% of patients whose chest wall was resected in continuity with the lung but in only 31% in whom an extrapleural resection was done. In the absence of lymph node metastasis, the 5 year survival rate of patients after en bloc resection of the chest wall was 50% compared with 33% for those with extrapleural resection (p less than 0.05). The finding of a peripheral lung tumor adherent to the parietal pleura indicates, in most instances, extension through the parietal pleura. When tumor is firmly adherent to the parietal pleura, an en bloc resection of the chest wall rather than an extrapleural dissection should be performed. This assures complete tumor removal and improves the probability of long-term survival. PMID- 1309469 TI - Foscarnet. PMID- 1309468 TI - Opioid agonists binding and responses in SH-SY5Y cells. AB - SH-SY5Y (human neuroblastoma) cultured cells, known to have mu-opioid receptors, have been used to assess and compare the ability of eight representative mu selective compounds from diverse opioid families to recognize and activate these receptors. A wide range of receptor affinities spanning a factor of 10,000 was found between the highest affinity fentanyl analogs (Ki = 0.1nM) and the lowest affinity analog, meperidine (Ki = 1 microM). A similar range was found for inhibition of PGE1-stimulated cAMP accumulation with a rank order of activities that closely paralleled binding affinities. Maximum inhibition of cAMP accumulation by each compound was about 80%. Maximum stimulation of GTPase activity (approximately 50%) was also similar for all compounds except the lowest affinity meperidine. Both effects were naloxone reversible. These results provide further evidence that mu-receptors are coupled to inhibition of adenylate cyclase and that the SH-SY5Y cell line is a good system for assessment of mu-agonists functional responses. PMID- 1309470 TI - Special reports on awareness of AIDS and HIV among racial and ethnic minority groups. PMID- 1309471 TI - [Consensus conference diagnosis lung carcinoma]. PMID- 1309472 TI - New considerations in treatment of urinary tract infections in adults. AB - Urinary tract infections remain some of the most common infections observed in community- and hospital-based practices. Although most infections continue to be caused by enteric bacteria, a growing proportion of these infections are caused by pathogens often associated with sexually transmitted diseases, including those of nonbacterial and viral etiologies. Consequently, multiresistant strains have become more prevalent, and the clinician must respond with a rational approach to therapy, based on the selection of an effective and well-tolerated antibiotic. The emergence of the newer antibiotic classes, including the second and third generation cephalosporins and the fluoroquinolones, has provided the clinician with agents that offer a broad spectrum of activity, good patient acceptance, a well-tolerated safety profile, and convenient dosage regimens due to their unique pharmacokinetic profiles. These drugs may be effective in single- or multiple dose regimens, depending on the condition being treated, and these should be considered important drugs in the treatment of uncomplicated and complicated adult urinary tract infections. PMID- 1309473 TI - Effect of oat gum on postprandial hyperglycemia. PMID- 1309474 TI - Dose-response effects of dietary gamma-linolenic acid-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. AB - The dose-dependent effect of dietary supplemented gamma-linolenic acid (GLA, 18:3n-6)-enriched borage oil (Bor) and black-currant oil on the ability of calcium ionophore-activated human polymorphonuclear neutrophils (PMN) to generate leukotriene B4 (LTB4) was investigated in adult healthy human volunteers. Significant (P less than 0.05) elevation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6), an elongation product of GLA, was revealed in PMN phospholipids after ingestion of either 0.48 or 1.5 g GLA-enriched oil/d. This elevation of DGLA in the PMN phospholipids paralleled the decreased capacity of calcium ionophore activated PMN to generate LTB4. Although the inhibition of LTB4 was greater with the ingestion of 1.5 g GLA-enriched BOR/d, it was not significantly different from the ingestion of 0.48 g/d. Taken together, dietary ingestion of GLA fortified oils does modulate PMN generation of proinflammatory LTB4. PMID- 1309475 TI - Cornstarch fermentation by the colonic microbial community yields more butyrate than does cabbage fiber fermentation; cornstarch fermentation rates correlate negatively with methanogenesis. AB - Fermentations of cornstarch and a cabbage-fiber preparation by human fecal suspensions were studied. The molar percent of butyrate of total short-chain fatty acid products was significantly higher when cornstarch was the substrate. Higher molar percents of butyrate were also produced from cornstarch as compared with endogenous substrate when rat fecal suspensions were used. A range of cornstarch fermentation rates was found with suspensions from 20 human subjects. Rapid fermentaion was associated with the absence of methane production. Methane negative rat fecal suspensions also fermented cornstarch more rapidly than did methane-positive suspensions. High butyrate production may be important because butyrate provides energy to colonocytes and it regulates differentiation of cultured cells. PMID- 1309477 TI - Plasma beta-carotene response in humans after meals supplemented with dietary pectin. AB - The purpose of this study was to determine the effect of pectin on plasma response to beta-carotene in humans. Using a crossover design, we evaluated the effect on plasma beta-carotene in seven subjects when 12 g citrus pectin was added to a 2092 kJ (500 kcal) controlled meal with 25 mg beta-carotene. Plasma samples were collected at 0, 8, 30, 48, and 192 h after the meals. Plasma beta carotene was quantified with the use of HPLC. The increase in plasma beta carotene concentration was significantly reduced by pectin at 30 and 192 h (paired t test; P less than 0.005 and less than 0.05, respectively). Mean percent increase in plasma beta-carotene concentration at 30 h after the meal with beta carotene was reduced by more than one-half when pectin was added to the meal. These results indicate that the inhibitory effect of pectin may provide one explanation for observations of reduced plasma beta-carotene response in humans after the ingestion of carotenoid-rich foods when compared with equivalent doses of beta-carotene supplements. PMID- 1309476 TI - Effects of oat bran, rice bran, wheat fiber, and wheat germ on postprandial lipemia in healthy adults. AB - Six normolipidemic males ingested on separate days a low-fiber test meal [2.8 g dietary fiber (TDF)] containing 70 g fat and 756 mg cholesterol, enriched or not with 10 g TDF as oat bran, rice bran, or wheat fiber or 4.2 g TDF as wheat germ. Fasting and postmeal blood samples were obtained for 7 h and chylomicrons were isolated. Adding fibers to the test meal induced no change in serum glucose or insulin responses. The serum triglyceride response was lower (P less than or equal to 0.05) in the presence of oat bran, wheat fiber, or wheat germ and chylomicron triglycerides were reduced with wheat fiber. All fiber sources reduced chylomicron cholesterol. Cholesterolemia decreased postprandially for 6 h and was further lowered in the presence of oat bran. Serum apolipoprotein (apo) A 1 and apo B concentrations were not affected. Thus, dietary fibers from cereals may reduce postprandial lipemia in humans to a variable extent. PMID- 1309478 TI - Overview of adrenergic anorectic agents. AB - Adrenergic anorexic agents of the amphetamine class suppress appetite and reduce body weight via activation of beta-adrenergic and/or dopaminergic receptors within the perifornical hypothalamus (PFH). Although phenylpropanolamine (PPA) is often considered to be a member of the amphetamine class of anorexiants, this drug is an atypical adrenergic anorexiant. Unlike amphetamine, microinjection of PPA into the PFH does not suppress feeding. Moreover, PPA anorexia is not reversed by the dopamine antagonist haloperidol. The anorexic action of PPA may result, in part, from its interaction with alpha 1-adrenergic receptors within the paraventricular medial hypothalamus (PVN). This hypothesis is supported by prior research, which documents that PPA is a direct-acting agonist predominantly at alpha 1 adrenoceptors, that microinjections into the PVN of the alpha 1 adrenoceptor agonists PPA and l-phenylephrine suppress feeding, and that injections of alpha 1-adrenoceptor antagonists within the PVN enhance feeding behavior. PMID- 1309479 TI - The human beta 3-adrenergic receptor: relationship with atypical receptors. AB - Atypical beta-adrenergic receptors (beta AR), different from beta 1 and beta 2ARs, have been suggested to modulate energy expenditure. We have characterized a gene coding for a third human beta AR, beta 3AR, whose sequence is 402 amino acids long and is 50.7% and 45.5% homologous to that of the human beta 1 and beta 2AR, respectively. The KD of [125I]-iodocyanopindolol for beta 3AR is 10-fold higher than for beta 1 or beta 2AR. The receptor has an apparent molecular weight of 65,000. Agonists for the beta 3AR induce cyclic AMP accumulation. Among 11 beta antagonists tested, only ICI118551 and CGP20712A, previously classified as, respectively, beta 1 and beta 2 selective, inhibit this effect. The beta 1 and beta 2 antagonists pindolol, oxprenolol, and CGP12177 are agonists of the beta 3AR. The potency order of beta agonists at beta 3 sites correlates with that for stimulation of lipolysis in rat fat tissues. Moreover, because beta 3AR mRNA was detected in rodent adipose tissues, liver, and muscle, we propose that the beta 3AR participates to the control by catecholamines of energy expenditure. PMID- 1309480 TI - Adrenergic receptor function in fat cells. AB - All classical adrenoceptor subtypes are functionally expressed in fat cells. However, only beta 1 adrenoceptors appear to be present in all types of fat cells. There is a substantial adrenoceptor reserve in fat cells; approximately 50% of beta and alpha 2 adrenoceptors are spare receptors. Beta adrenoceptors are subject to intensive regulation. They are regulated by insulin, estrogens, and androgens as well as by thyroid hormones and are altered by nutritional factors, diabetes, autonomic neuropathy, and beta-blocking treatment. Alpha receptors are less sensitive to changes except during infancy, when there are marked developmental alterations in the function of alpha 2 adrenoceptors, and during fasting, when there is a decrease in receptor expression. In addition, beta adrenoceptors but not alpha 2 adrenoceptors are sensitive to homologous desensitization after exposure to agonists. Site variations in the expression and function of beta and alpha 2 adrenoceptors, which in part are situated at the level of gene transcription, may be involved in the development of regional obesity. PMID- 1309481 TI - Hodgkin's disease in monocytoid B-cell clusters and cytomegalovirus lymphadenitis. PMID- 1309482 TI - Hepatitis C virus, antibodies, and infectivity. Paradox, pragmatism, and policy. PMID- 1309483 TI - The comparative test performance of dot filter hybridization (Viratype) and conventional morphologic analysis to detect human papillomavirus. AB - To investigate the test performance of a commercially available detection kit for human papillomavirus (HPV), the relationship between the detection of HPV by dot filter hybridization (DFH) and by standard morphologic methods was studied. Four hundred two cervical samples taken from 381 patients referred to a colposcopy clinic were examined. Human papillomavirus DNA sequences were identified and typed using commercially available anti-sense RNA probes. Simultaneous cytologic smears were obtained in 289 patients, directed biopsy samples in 284, and both smears and biopsy samples in 171 samples. Human papillomavirus DNA was detected in 164 specimens (41%), of which 24 (15%) were type 6/11, 74 (45%) were type 16/18, 39 (24%) were type 31/33/35, and 27 (16%) were untyped due to the presence of multiple positive signals. Viral types 16/18 and 31/33/35 were eight and six times more frequent in cervical intraepithelial neoplasia (CIN) II/CIN III lesions than in condyloma/CIN I, respectively. When the cytologic diagnosis was considered the standard of reference, the results of DFH for the detection of HPV were concordant in 167 (56%) paired samples. The sensitivity of DFH was 48% and the specificity was 77%. The distribution of the morphologic diagnoses in the group of false-negative results and true-positive results was similar. When the histologic diagnosis was considered the standard of reference, the efficiency of DFH was 62%, the sensitivity was 59%, and the specificity was 79%. In the subgroup of 118 samples with simultaneous smear and biopsy and at least one positive examination, 42 (36%) were positive by all three methods, 42 (36%) by two, and 34 (29%) by one, including 6 (5%) by DFH alone. Fifteen cases more were detected by the complementary use of DFH and cytology than with cytology alone. The results demonstrated that the sets of patients positive for HPV when detected by DFH or by morphologic methods were not identical but rather overlapped. The detection of HPV may be slightly improved by using DFH in addition to conventional examinations. A significant number of HPV-positive patients without a morphologic lesion and patients with low-grade lesions had HPV 16/18 or 31/33/35, suggesting a possible role for typing in establishing a risk profile. However, given uncertainties in understanding the biology of HPV-associated lesions, the role, if any, of clinical testing for HPV by DFH remains to be defined. PMID- 1309484 TI - Chronic fatigue syndrome: a conundrum. AB - Chronic fatigue syndrome (CFS) is a multi-faceted disorder for which no etiology has been determined. This paper discusses the implications of the new clinical case definition of CFS on previous and future studies of this illness. The authors' own management approach is also discussed. PMID- 1309485 TI - Chromosome alterations contribute to neoplastic progression of transformed rat embryonal fibroblasts. AB - Three types of transformants derived from rat embryonal fibroblasts (REFs) corresponding to the different progressional stages were obtained: TF1 (human papillomavirus type 16 E7 (HPV16 E7) transfection alone) and TF2 (E7 plus adenovirus type 12(Ad12) E1b were immortalized, TF3 (E7 plus adenovirus type 5 (Ad5) E1B) was anchorage-independent but not tumorigenic, and TF4 (E7 plus EJ ras) was tumorigenic. Cytogenetic investigations revealed that the cells carrying specific chromosomal abnormalities expanded clonally in three of the five TF4 tumorigenic clones, in contrast to the TF1-TF3 non-tumorigenic clones, which showed a normal karyotype. By the inoculation of TF4 into syngeneic rats, 8 tumor derived clones were obtained. Clonal expansion of cells carrying specific chromosome changes was also remarkable in these tumor-derived clones. However, the type of rearrangements and the chromosomes involved in the abnormalities were not identical. In addition, it was shown that chromosome constitutions of the parental TF4 transformants were apparently inconsistent with those of their tumor derived clones. However, the clonal nature of abnormalities observed in the parental and the tumor-derived clones suggested that these genetic events of cellular genomes corresponded with and possibly contributed to the progression of malignant phenotypes of cells. PMID- 1309486 TI - INT1 and GLI genes are not rearranged or amplified in benign pleomorphic adenomas with chromosome abnormalities of 12q13-15. AB - A subgroup of pleomorphic adenomas of the salivary glands is characterized by translocations involving chromosome 12, with consistent breakpoints at 12q13-15. Two proto-oncogenes, INT1 and GLI, have been assigned to this region of chromosome 12. We studied the possible involvement of these genes in pleomorphic adenomas with different karyotypic abnormalities, including cases with involvement of 12q13-15. Using detailed restriction fragment analysis of tumor DNAs from 25 cases, we found no evidence of rearrangement or amplification of INT1 or GLI. Because we previously found an adenoma with a del(12)(q13q15), we also analyzed normal and tumor DNAs from the 25 tumors separately to identify possible allelic losses at the GLI locus. Thirteen of the 25 tumors were informative, and none of these showed evidence of allelic losses. Collectively, these findings indicate that neither the INT1 nor the GLI gene appears to be the primary target gene for the translocations and deletions involving the 12q13-15 region in pleomorphic adenomas. PMID- 1309487 TI - Increased proliferation of activated T-lymphocytes in response to a monoclonal antibody (anti-p68). AB - A series of monoclonal antibodies was produced by immunization of mice with cells of the human promonocytic cell line CM-S; one of these recognized a membrane antigen (MW 68,000) constitutively expressed by these cells. Antigen p68 was also found to be expressed on all granulocytic cells and most mononuclear leukocytes from normal human peripheral blood, but not on hemopoietic precursor cells from bone marrow. Various types of leukemic cells also expressed antigen p68 as did various transformed human cell lines whether derived from hemopoietic cells or from other tissues. Antigen p68 is involved in T-lymphocyte regulation. In fact, the antibody anti-p68 has a strong synergistic effect increasing the proliferative response of peripheral blood T-lymphocytes both in the mixed lymphocyte reaction and when the lymphocytes are stimulated by suboptimal doses of lectin (phytohemagglutinin), tumor promoter phorbol esters, or tetanus toxoid. The anti-p68 antibody synergizes with the active metabolite of vitamin D3, 1,25 dehydroxyvitamin D3, to induce monocyte to macrophage maturation and enhances the function of mature granulocytes stimulated with the granulocyte-macrophage colony stimulating factor in vitro. PMID- 1309488 TI - Production of tumor necrosis factor-alpha by naive or memory T lymphocytes activated via CD28. AB - While it is well established that activated T cells can produce tumor necrosis factor alpha (TNF-alpha), it is less clear whether this function is confined to a given subset, e.g., memory cells. To approach this question, we investigated the production of TNF-alpha by human peripheral blood T lymphocytes activated with anti-CD28 mAb since this activation pathway is known to potentiate cytokine production. Under the culture conditions used, the amount of TNF-alpha produced was markedly enhanced compared to that obtained after activation with immobilized anti-CD3 mAb. The enhancement of TNF-alpha production was already apparent after incubation of T cells for 6 hr. Up to 5 ng/ml of TNF-alpha was measured on Day 2 in supernatants of cultures of 10(4) T lymphocytes. To determine the source of the cells producing high amounts of TNF-alpha, T lymphocytes were separated into two subpopulations, namely naive cells (expressing the CD45RA isoform) and memory cells (expressing the CD45RO isoform). While both subpopulations proliferated equally well after stimulation with anti-CD28 mAb, up to 90% of the TNF-alpha produced under these conditions originated from memory T cells. These results thus document that T cell activation via CD28 results in a marked increase in TNF alpha production without affecting the functional disparity that exists between naive and memory T cells. PMID- 1309489 TI - Newly synthesized class II MHC chains are required for VSV G presentation to CTL clones. AB - Mechanisms of antigen processing and presentation to thymus-derived lymphocytes have been under intense study for several years, focusing on both Class I restricted antigen presentation and Class II-MHC restricted responses. The studies described here examine the processing and presentation of exogenously provided soluble glycoprotein of the vesicular stomatitis virus and as well as newly synthesized viral glycoprotein. Evidence is provided that newly synthesized Class II MHC chains are required for cell surface expression of processed glycoprotein determinants irrespective of the origin of the viral antigen. Inhibitors of distinct cellular processes, including ammonium chloride, emetine, and Brefeldin A, have been used to dissect the pathways utilized. PMID- 1309490 TI - Effect of LTB4 on the inhibition of natural cytotoxic activity by PGE2. AB - NK activity is regulated by arachidonic acid metabolites. More precisely PGE2 and LTB4 decreases and increases respectively non-MHC-restricted cytotoxicity in humans. We have observed similar data in mice since NK activity was inhibited by PGE2 (10(-6) to 10(-8) M) and enhanced by LTB4 (10(-8) to 10(-12) M). On the other hand when PGE2 and LTB4 were combined during the same assay the lysis percentage was smaller than the one which was induced by PGE2 alone. Because PGE2 increases intracellular cyclic AMP and that LTB4 augments cyclic GMP we used a cAMP inducer (forskolin) and a cGMP analogue (8 Br-cGMP) instead of eicosanoids and we observed similar data (i.e., a decrease of natural killing) as when PGE2 was combined with LTB4. When splenocytes are cultured for 1-4 days alone, cytotoxic activity decreases unless they are cultured in the presence of indomethacin. Cytotoxic activity of spleen cells cultured in the presence of PGE2 or LTB4 is respectively decreased or increased. However, splenocytes that were cultured alone for at least 24 hr were no longer sensitive to inhibition by PGE2 but were still PGE2-sensitive when cultured in the presence of LTB4. PMID- 1309491 TI - Inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on Jurkat cells activated by phorbol ester and calcium ionophore. AB - The effects of syncytiotrophoblast plasma membrane vesicles (STPM) on stimulated Jurkat leukemic T cells have been investigated. STPM inhibited IL-2 production and the expression of protein P55 of the IL-2 receptor (IL-2R P55), when Jurkat cells were stimulated by a combination of calcium ionophore A23187 (CaI) + phorbol 12-myristate 13-acetate (PMA). STPM also inhibited IL-2R P55 when cells were stimulated by PMA alone, a situation in which IL-2 production is negligible. On the other hand, STPM had no effect on the sustained mobilization of intracellular Ca2+ induced by CaI nor on the PKC-dependent CD3 down regulation induced by PMA. Finally STPM had no effect on intracellular cAMP levels. These results show that (i) the inhibitory effect of STPM on IL-2R P55 expression is independent of the inhibition of IL-2 production, and (ii) the inhibitory effects of STPM are at least partially independent of phosphatidylinositol 4,5 bisphosphate hydrolysis. They suggest that STPM affect a signaling pathway activated by PMA but possibly PKC independent. PMID- 1309492 TI - Ulnar nerve decompression at the cubital tunnel. AB - A limited surgical decompression of the ulnar nerve within the cubital tunnel by incision of the arcuate ligament was effective in relieving pain and dysesthesia in 22 of 27 patients. No patient had any apparent muscle weakness or atrophy preoperatively. Twenty-five patients had evidence of compression of the ulnar nerve within the cubital tunnel at surgery, as noted by narrowing, hyperemia, or attachment of adhesions to the nerve. Three of four patients who had a subsequent anterior transposition obtained partial relief of symptoms. PMID- 1309493 TI - Intra-abdominal sepsis alters tumor necrosis factor-alpha and interleukin-1 beta binding to human neutrophils. AB - OBJECTIVE: To determine the effects of intraabdominal sepsis on polymorphonuclear leukocyte tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) receptor expression. DESIGN: Prospective, randomized comparison between patients undergoing elective colon surgery vs. patients with intra-abdominal sepsis. SETTING: Tertiary-care center with all patients with intra-abdominal sepsis in a surgical ICU environment. PATIENTS: Group 1 (n = 7) represents control patients who underwent elective colon surgery without intra-abdominal sepsis. Group 2 (n = 10) represents patients with intra-abdominal sepsis. MEASUREMENTS AND MAIN RESULTS: Polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression +/- stimulation of the oxidative burst was measured using 125I TNF-alpha and 125I IL-1 beta. Superoxide anion production and candicidal activity were measured in the presence of TNF-alpha and IL-1 beta. Group 2 patients expressed fewer TNF-alpha and IL-1 beta receptors on their cell surface, and stimulation of oxidative burst reduced TNF-alpha and IL-1 beta receptor expression in group 2 more than in group 1. Diminished TNF-alpha and IL 1 beta binding reduced superoxide anion production by group 2 polymorphonuclear leukocytes. Decreased TNF-alpha binding but not IL-1 beta, reduced polymorphonuclear leukocyte candicidal activity by group 2 polymorphonuclear leukocytes. CONCLUSIONS: a) Intra-abdominal sepsis reduces polymorphonuclear leukocyte TNF-alpha and IL-1 beta receptor expression. b) Expression of these surface receptors is altered by stimulation of the polymorphonuclear leukocyte oxidative burst. c) Diminished TNF-alpha and IL-1 beta receptor expression is associated with functional impairments in polymorphonuclear leukocyte activity. PMID- 1309494 TI - Lactic acidosis in critical illness. AB - PURPOSE: This article reviews the current body of knowledge regarding lactic acidosis in critically ill patients. The classification of disordered lactate metabolism and its pathogenesis are examined. The utility of lactate as a metabolic monitor of shock is examined and current therapeutic strategies in the treatment of patients suffering from lactic acidosis are extensively reviewed. The paper is designed to integrate basic concepts with a current approach to lactate in critical illness that the clinician can use at the bedside. DATA SOURCES: Comprehensive review of the available, basic science, medical, surgical, and critical care literature. CONCLUSIONS: The severity of lactic acidosis in critically ill patients correlates with overall oxygen debt and survival. Lactate determinations may be useful as an ongoing monitor of perfusion as resuscitation proceeds. Therapy of critically ill patients with lactic acidosis is designed to maximize oxygen delivery in order to reduce tissue hypoxia by increasing cardiac index, while maintaining hemoglobin concentration. Buffering agents have not been shown to materially affect outcome from lactic acidosis caused by shock. The benefits of other specific therapies designed to reduce the severity of lactic acidosis remain unproven. PMID- 1309495 TI - Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis. AB - Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease. PMID- 1309496 TI - Endogenous digoxin-like immunoreactive factor is elevated in advanced chronic respiratory failure. AB - Digoxin-like immunoreactive factor (DLIF) is an endogenous substance with natriuretic and diuretic activity. Elevated plasma levels of DLIF are found in various clinical states characterized by water and sodium retention. Chronic respiratory failure, particularly of an advanced stage, also is frequently associated with water and sodium retention. In order to determine whether elevated plasma levels of DLIF are present in chronic respiratory failure, we measured plasma DLIF levels in seven patients (four with COPD [two of whom had associated sleep apnea disturbance] and three with kyphoscoliosis) suffering from advanced chronic respiratory failure with severe hypoxemia and hypercapnia. We found that in these patients plasma levels of DLIF were significantly higher than in healthy control subjects. We conclude that patients with advanced chronic respiratory failure respond with increased levels of DLIF. This may represent an attempt at homeostasis of water and sodium metabolism which is frequently deranged in this clinical condition. PMID- 1309497 TI - Small cell lung cancer presenting as a solitary pulmonary nodule. PMID- 1309498 TI - Cardiac metastasis of hepatocellular carcinoma mimicking pericardial effusion on radionuclide angiocardiography. AB - A 51-year-old man presented with exertional dyspnea for two months. He had a history of hepatocellular carcinoma that was totally resected three years earlier. Radionuclide angiocardiography disclosed a large photopenic area separating the heart from the liver, and lung blood pools mimicking a large pericardial effusion. Echocardiography and magnetic resonance imaging of the heart, however, showed extensive tumor infiltration of the myocardium of both ventricles. Endomyocardial biopsy confirmed the diagnosis of metastatic hepatocellular carcinoma. There was no evidence of recurrent hepatoma in the liver. PMID- 1309499 TI - Umbilical metastasis from small cell carcinoma of the lung. AB - Umbilical metastases have been almost exclusively reported in patients with adenocarcinomas of intra-abdominal organs. We present a case of small cell carcinoma of the lung with umbilical metastasis that was confirmed by biopsy. To our knowledge, this is the first reported case of umbilical metastasis from small cell lung cancer. PMID- 1309500 TI - Semiquantitative measurement of cytomegalovirus DNA in lung and heart-lung transplant patients by in vitro DNA amplification. AB - We report the cases of two lung transplant recipients (one heart-lung and one single lung) who eventually developed cytomegalovirus (CMV) pneumonitis after documentation of increasing CMV DNA titers in sequential bronchoalveolar lavage (BAL) specimens by polymerase chain reaction (PCR) amplification. To our knowledge, this is the first report that semiquantitation of PCR-amplified DNA can detect an increase in CMV DNA titer in BAL specimens prior to the onset of clinical symptoms or detection of infection by traditional techniques in lung transplant patients. The results obtained in these two cases suggest that DNA titer measurement on sequential BAL samples may differentiate latency from active viral replication and, thus, provide an opportunity for clinical intervention before the development of overt clinical symptoms. PMID- 1309501 TI - Functional and morphological changes induced by tunicamycin in dividing and confluent endothelial cells. AB - Cultured bovine aortic endothelial cells treated with tunicamycin, an inhibitor of glycoprotein synthesis, developed a concentration-dependent inhibition of N acetylglucosamine-1-phosphate transferase activity, and this inhibition was correlated with a substantial decrease in [3H]mannose incorporation by the cells. Endothelial cells were very sensitive to tunicamycin, and changes in their morphology occurred as a result of the inhibition of glycoprotein synthesis. The cells became elongated, the surface irregular, roughened, and granular, and there was an increase in the interstitial space between the cells. Electron dense material was accumulated within and dilated the rough endoplasmic reticulum, and the distribution of the glycoproteins laminin and fibronectin throughout the endothelial cell monolayer was modified. These morphological changes coincided with functional impairment with the permeability of endothelial cell monolayers to both 125I-albumin and [3H]inulin being increased by treatment with tunicamycin (10(-6) M) for 24 h. These results indicate that the synthesis of glycoproteins is crucial for cell-cell adhesion and the functional properties of the endothelial lining of blood vessels. PMID- 1309502 TI - A temperature-sensitive CHO-K1 cell mutant (tsTM13) defective in chromosome decondensation and spindle deconstruction in M phase. AB - A temperature-sensitive CHO-K1 cell mutant, tsTM13, exhibited a delayed cell cycle progression from metaphase to telophase at a nonpermissive temperature and was finally arrested from anaphase to telophase. Metaphase chromosomes were overcondensed and chromosome disjunction in anaphase was uncoordinated. In telophase, sister chromatids were segregated and cytokinesis was completed, but chromosome structure remained in a condensed state and the spindle was not deconstructed. The level of phosphorylation of histones H1 and H3 remained high in the later stages of mitosis and the activity of histone H1 kinase was also maintained at a high level. These results strongly suggest that the pleiotropic defects of tsTM13 cells in mitosis are associated with a lack of inactivation of activated histone H1 kinase. PMID- 1309503 TI - Calcium-regulated phosphorylation of proteins in the membrane-matrix compartment of the Chlamydomonas flagellum. AB - Crosslinking of surface-exposed domains on certain Chlamydomonas flagellar membrane glycoproteins induces their movement within the plane of the flagellar membrane. Previous work has shown that these membrane glycoprotein movements are dependent on a critical concentration of free calcium in the medium and are inhibited reversibly by calcium channel blockers and the protein kinase inhibitors H-7, H-8, and staurosporine. These observations suggest that the flagellum may use a signaling pathway that involves calcium-activated protein phosphorylation to initiate flagellar membrane glycoprotein movements. In order to pursue this hypothesis, we examined the calcium dependence of phosphorylation of flagellar membrane-matrix proteins using an in vitro system containing [gamma 32P]ATP or [35S]ATP gamma S. Using only endogenous enzymes and endogenous substrates found in the membrane-matrix fraction obtained by extraction of flagella with 0.05% Nonidet P-40, we observed both calcium-independent protein phosphorylation and calcium-dependent protein phosphorylation in addition to an active protein dephosphorylation activity. Addition of micromolar free calcium increased the amount of protein phosphorylation severalfold. Calcium-activated protein kinase activity was inhibited by H-7, H-8, and staurosporine, the same protein kinase inhibitors that inhibit the calcium-dependent glycoprotein redistribution in vivo. A small group of polypeptides in the 26-58 kDa range exhibited a dramatic increase in phosphorylation in the presence of 20 microM free calcium. We suggest that Chlamydomonas utilizes the intraflagellar free calcium concentration to regulate the phosphorylation of specific flagellar proteins in the membrane-matrix fraction, one or more of which may be involved in regulating the machinery responsible for flagellar membrane glycoprotein redistribution. PMID- 1309504 TI - Mitogenic growth factors regulate differentially early gene mRNA expression: a study on two clones of 3T3 fibroblasts. AB - The relationship between cell proliferation and mRNA levels of the immediate early genes c-fos, c-jun, and jun B has been investigated in two clones of 3T3 fibroblasts (D1-3T3 and N2-3T3) upon treatment with basic fibroblast growth factor (bFGF), thrombin, phorbol 12-myristate 13-acetate (PMA) and dibutyryl cyclic AMP (Bt2cAMP). The 3T3-derived clone D1-3T3 almost stops dividing upon serum deprivation, while the N2-3T3 clone does not. The proliferation of the two clones was stimulated by thrombin and PMA and inhibited by Bt2cAMP. Basic FGF stimulated the growth of D1-3T3 but partly inhibited that of N2-3T3 cells. In spite of variable mitogenic response, immediate early genes, c-fos, c-jun, jun B, and c-myc, were induced by the growth factors and by PMA in both cell clones. In our experimental conditions the early gene mRNAs were expressed independently; i.e., the expression of one protooncogene had no bearing on the expression of the other. The cell growth was not directly related to the expression of a particular protooncogene mRNA. Data are presented showing that early gene mRNA expression induced by bFGF or thrombin was not mediated by protein kinase C activation while thrombin-induced mitosis was. Basic FGF induced a part of c-jun mRNA expression, but not mitosis, through a pertussis toxin-sensitive mechanism. PMID- 1309505 TI - The molecular cloning and expression of two CRABP cDNAs from human skin. AB - Retinoic acid (RA) is known to have a profound effect on the growth and differentiation of human epidermal cells in vivo and in vitro. One of the proteins thought to be involved in mediating the action of RA is the cellular retinoic acid-binding protein (CRABP). We have used PCR technology to generate cDNAs for two distinct CRABPs from human skin and skin-derived cells. One is highly homologous to the CRABP I cDNAs previously cloned from bovine and murine sources. The second shares extensive deduced amino acid homology with CRABP II, a protein recently described in newborn rat and embryonic chick. Although both mRNAs can be detected in neonatal foreskin, CRABP II mRNA is the predominant one in this tissue, as well as in cultured newborn fibroblasts and keratinocytes. Northern blot analysis showed CRABP II mRNA level was only slightly reduced by addition of 10(-6) or 10(-5) M RA to cultures of neonatal foreskin-derived fibroblasts, as was the CRABP I mRNA level in cultured human gut epithelial cells. In contrast, expression of CRABP II mRNA by cultured neonatal keratinocytes was strongly downregulated by RA. We conclude that CRABP II is the predominant CRABP in human skin, at least in the newborn period, and that it is differentially regulated in fibroblasts versus keratinocytes. Our data are consistent with a role for CRABP in regulating the amount of RA delivered to the nucleus. PMID- 1309506 TI - An activator of protein kinase C inhibits gap junction communication between cultured bovine lens cells. AB - Currently little is known about the regulation of gap junction communication in the lens. We report here on the effects of the protein kinase C activator, 12-O tetradecanoylphorbol-13-acetate (TPA), on cultured bovine lens cells which appeared to be epithelial in nature. Dramatically reduced intercellular transfer of the fluorescent dye Lucifer yellow was observed when the cultured lens cells were treated with octanol, a known inhibitor of gap junction communication. TPA (4 beta isomer) was also shown to reduce intercellular permeability within these cultures. In contrast, an inactive form of TPA, 4 alpha-TPA, did not decrease dye transfer. Permeability was evaluated in terms of both the number of cells receiving dye and the rate of decrease in fluorescence intensity in the injected cell. The maximum decreases in dye transfer occurred at 2 h of TPA treatment and dye transfer gradually increased to control levels over a time course of many hours. Incubation of cultures with 32Pi and immunoprecipitation using antibodies to the N- and C-terminal regions of connexin43 demonstrated a gap junction phosphoprotein of 43,000 Da. Phosphorylation of connexin43 increased during the first 2 h of TPA treatment. These results suggest that protein kinase C has a direct or indirect effect on gap junction communication in cultured lens cells. PMID- 1309507 TI - The transcription of MyoD1 and myogenin genes in thymic cells in vivo. AB - The skeletal muscle specific genes MyoD1 and myogenin are closely associated with commitment of cells to the myogenic lineage and differentiation of skeletal muscle precursor cells. The transcription of these genes was studied in the thymus where mononuclear cells termed myoid cells appear to closely resemble skeletal muscle precursors. In thymus from adult SJL/J and BALB/c mice, in situ hybridization with either MyoD1 or myogenin riboprobes showed probe-positive cells concentrated in the medullary region. In neonatal thymus, mRNA for these genes was not detected. These data are the first demonstration in a higher vertebrate of MyoD1 and myogenin expression in a tissue other than skeletal muscle. The sustained expression of MyoD1 and myogenin genes in thymi of adult mice shows that myoid cells are not equivalent to quiescent stem cells of mature skeletal muscle. In addition, studies with antistriational antibodies indicate that myoid cells do not continue to differentiate within the normal murine thymic environment. This arrested differentiation process presents an unusual model for investigating conditions regulating myogenesis in vivo. PMID- 1309508 TI - Mechanisms that generate junctional diversity in alpha and delta chains that use the Tcrd-V3 gene product. AB - The signals that dictate whether a thymocyte will express the alpha beta or gamma delta T-cell receptors are unknown. Although it is also not known if these two different cell types use identical recombinational machinery during rearrangement, the same variable (V) region genes can be used by both alpha and delta chains. By examining the products of rearrangements in alpha beta or gamma delta thymocytes that express identical V genes, we hoped to determine whether these cell types might differ in particular aspects of their recombinational activity. The polymerase chain reaction was used to show that the Tcrd-V2, Tcrd V3, and Tcra-V3 genes are expressed as both Tcra and Tcrd transcripts in fetal and adult BALB/c mice. Sequencing of V delta 3 isolates was performed in order to compare the contribution of various mechanisms to the generation of junctional diversity. Extensive junctional diversity was present at all stages of development examined (fetal, newborn, and adult). During early development both alpha and delta chain junctional diversity is generated primarily by variability in the position of joining two gene segments (i.e., Tcrd-V3 to Tcra-J in alpha chains; Tcrd-V3 to Tcrd-D2 and Tcrd-D2 to Tcrd-J1 in delta chains). The pattern of base pair deletion from the end of the Tcrd-V3 gene was identical in alpha and delta chains and deletions occurred in fetal as well as adult T cells. In later development T cells use not only this mechanism for alpha and delta chains but also the addition of bases at gene segment junctions, presumably through the action of terminal deoxynucleotidyl transferase (TdT). Finally, a comparison of the variable domains of these alpha and delta chains shows that a notable difference is the variability in length of the CDR 3 region which can be significantly longer in delta-chains than in alpha-chains. PMID- 1309509 TI - Identification of a cDNA encoding the rat CD28 homologue. PMID- 1309510 TI - Siderophore production and membrane alterations by Bordetella pertussis in response to iron starvation. AB - Bordetella pertussis was grown in iron (Fe)-free defined medium to limit the growth of the organism. Doubling times of the Fe-starved organism increased by approximately 1 h, and a 40% reduction in the final extent of growth in Fe depleted medium was observed. Under these conditions, a hydroxamate siderophore named bordetellin was secreted by B. pertussis. Lactoferrin and transferrin supported growth of B. pertussis even when the protein was sequestered inside dialysis tubing. This suggested that binding of lactoferrin and transferrin to B. pertussis was not essential and that bordetellin production plays a major role in Fe uptake. Solid-phase dot blot assays indicated weak binding of lactoferrin to the cell surface, consistent with previous reports of a lactoferrin receptor. Three new proteins of 97, 77, and 63 kDa were synthesized in response to Fe starvation. Fe-inducible proteins of 103, 72, 24, 21, and 18 kDa were also observed. The synthesis of lipopolysaccharide was also altered by Fe availability. PMID- 1309511 TI - Spontaneous insertion of an IS1-like element into the virF gene is responsible for avirulence in opaque colonial variants of Shigella flexneri 2a. AB - Colonial variation of Shigella flexneri serotype 2a from the translucent (2457T) to the opaque form (2457O) occurs spontaneously once in 10(4) cell divisions, with concomitant loss of ipa gene expression and virulence. The appearance of 2457O was associated with the insertional inactivation of virF, an invasion plasmid-encoded positive regulator of ipa gene expression. Plasmid pWR110, a Tn5 tagged invasion plasmid that restores the invasive phenotype to plasmid-cured Shigella derivatives, was conjugally transferred into 2457O. Synthesis of the invasion-associated IpaB and IpaC polypeptides, normally present on the surface of virulent shigellae, and the invasive phenotype were restored in 2457O(pWR110) transconjugants. Plasmid DNA restriction endonuclease patterns of 2457T and 2457O, along with hybridization analysis, showed that a SalI fragment carrying the virF gene in 2457O had increased in size relative to its counterpart in 2457T. Analysis of virF DNA sequences amplified by the polymerase chain reaction revealed that the virF sequence from 2457O was 780 bp larger than that amplified from 2457T. Moreover, the virF sequence amplified from 2457O hybridized to an IS1 DNA probe whereas the amplified 2457T virF sequence did not. DNA sequence analysis mapped the insertion element, designated IS1SFO, within an A.T-rich region of the virF open reading frame and identified a 9-bp virF target sequence that was duplicated at the insertion site of IS1SFO. The DNA sequence of IS1SFO was greater than 99% homologous to IS1F. Plasmid pWR600, carrying a 1,260-bp HpaII fragment encoding a wild-type virF gene, was able to restore the virulent phenotype and translucent colonial morphology to nine independently isolated 2457O hosts. PMID- 1309512 TI - Pertussis toxin partially inhibits phagocytosis of immunoglobulin G-opsonized Staphylococcus aureus by human granulocytes but does not affect intracellular killing. AB - The aim of the present study was to determine whether pertussis toxin (PT) sensitive GTP-binding proteins (G proteins) are involved in the signal transduction pathway(s) used for phagocytosis and intracellular killing of bacteria by human granulocytes. Treatment of granulocytes with PT resulted in decreased phagocytosis of immunoglobulin G (IgG)-opsonized Staphylococcus aureus but did not affect subsequent intracellular killing of these bacteria. PT also caused a decrease in the extracellular release of superoxide anion (O2-) and hydrogen peroxide (H2O2) by granulocytes in response to S. aureus opsonized by IgG. However, neither the phagocytosis nor the intracellular killing of S. aureus opsonized by fresh serum was affected by PT, and the release of O2- was partially inhibited. The release of O2- in response to serum-treated zymosan, opsonized mainly by complement components, was also only partially inhibited by PT. It is therefore possible that PT inhibits responses mediated through complement receptors to a lesser extent than those mediated via Fc gamma receptors. The results of this study indicate that PT-sensitive G proteins are involved in the signal transduction pathways that mediate the phagocytosis of IgG-opsonized bacteria and the accompanying respiratory burst. PMID- 1309513 TI - Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. AB - The lecithinase gene of the intracellular pathogen Listeria monocytogenes, plcB, was identified in a 5,648-bp DNA fragment which expressed lecithinase activity when cloned into Escherichia coli. This fragment is located immediately downstream of the previously identified gene mpl (prtA). It contains five open reading frames, named actA, plcB, and ORFX, -Y, and -Z, which, together with mpl, form an operon, since a 5.7-kb-long transcript originates from a promoter located upstream of mpl (J. Mengaud, C. Geoffroy, and P. Cossart, Infect. Immun. 59:1043 1049, 1991). A second promoter was detected in front of actA which encodes a putative membrane protein containing a region of internal repeats. plcB encodes the lecithinase, a predicted 289-amino-acid protein homologous to the phosphatidylcholine-specific phospholipases C of Bacillus cereus and Clostridium perfringens (alpha-toxin). plcB mutants produce only small plaques on fibroblast monolayers, and an electron microscopic analysis of infected macrophages suggests that lecithinase is involved in the lysis of the two-membrane vacuoles that surround the bacteria after cell-to-cell spread. On the opposite DNA strand, downstream of the operon, three more open reading frames, ldh, ORFA, and ORFB, were found. The deduced amino acid sequence of the first one is homologous to lactate dehydrogenases. Low-stringency Southern hybridization experiments suggest that these three open reading frames lie outside of the L. monocytogenes virulence region: mpl and actA were specific for L. monocytogenes, sequences hybridizing to plcB were detected in L. ivanovii and L. seeligeri, and sequences hybridizing to ORFX, -Y, and -Z were found in L. innocua. In contrast to this, sequences hybridizing to ldh or ORFB were detected in all Listeria species (including the nonpathogenic ones). PMID- 1309514 TI - Hydrogen-oxidizing electron transport components in the hyperthermophilic archaebacterium Pyrodictium brockii. AB - The hyperthermophilic archaebacterium Pyrodictium brockii grows optimally at 105 degrees C by a form of metabolism known as hydrogen-sulfur autotrophy, which is characterized by the oxidation of H2 by S0 to produce ATP and H2S. UV-irradiated membranes were not able to carry out the hydrogen-dependent reduction of sulfur. However, the activity could be restored by the addition of ubiquinone Q10 or ubiquinone Q6 to the UV-damaged membranes. A quinone with thin-layer chromatography migration properties similar to those of Q6 was purified by thin layer chromatography from membranes of P. brockii, but nuclear magnetic resonance analysis failed to confirm its identity as a ubiquinone. P. brockii quinone was capable of restoring hydrogen-dependent sulfur reduction to UV-irradiated membranes. Hydrogen-reduced-minus-air-oxidized absorption difference spectra on membranes revealed absorption peaks characteristic of c-type cytochromes. A c type cytochrome with alpha, beta, and gamma peaks at 553, 522, and 421 nm, respectively, was solubilized from membranes with 0.5% Triton X-100. Pyridine ferrohemochrome spectra confirmed its identity as a c-type cytochrome, and heme staining of membranes loaded on sodium dodecyl sulfate gels revealed a single heme-containing component of 13 to 14 kDa. Studies with the ubiquinone analog 2-n heptyl-4-hydroxyquinoline-N-oxide demonstrated that the P. brockii quinone is located on the substrate side of the electron transport chain with respect to the c-type cytochrome. These first characterizations of the strictly anaerobic, presumably primitive P. brockii electron transport chain suggest that the hydrogenase operates at a relatively high redox potential and that the H2 oxidizing chain more closely resembles those of aerobic eubacterial H2-oxidizing bacteria than those of the H2-metabolizing systems of anaerobes or the hyperthermophile Pyrococcus furiosus. PMID- 1309515 TI - In vitro repair of double-strand breaks accompanied by recombination in bacteriophage T7 DNA. AB - A double-strand break in a bacteriophage T7 genome significantly reduced the ability of that DNA to produce viable phage when the DNA was incubated in an in vitro DNA replication and packaging system. When a homologous piece of T7 DNA (either a restriction fragment or T7 DNA cloned into a plasmid) that was by itself unable to form a complete phage was included in the reaction, the break was repaired to the extent that many more viable phage were produced. Moreover, repair could be completed even when a gap of about 900 nucleotides was put in the genome by two nearby restriction cuts. The repair was accompanied by acquisition of a genetic marker that was present only on the restriction fragment or on the T7 DNA cloned into a plasmid. These data are interpreted in light of the double strand gap repair mode of recombination. PMID- 1309516 TI - Insertion and excision of Bacteroides conjugative chromosomal elements. AB - Many strains of Bacteroides harbor large chromosomal elements that can transfer themselves from the chromosome of the donor to the chromosome of the recipient. Most of them carry a tetracycline resistance (Tcr) gene and have thus been designated Tcr elements. In the present study, we have used transverse alternating field electrophoresis to show that all but one of the Tcr elements screened were approximately 70 to 80 kbp in size. The exception (Tcr Emr 12256) was 150 to 200 kbp in size and may be a hybrid element. All of the Tcr elements inserted in more than one site, but insertion was not random. The Tcr elements sometimes cotransfer unlinked chromosomal segments, or nonreplicating Bacteroides units (NBUs). Transverse alternating field electrophoresis analysis showed that insertion of NBUs was not random and that the NBUs did not insert near the Tcr element. Although attempts to clone one or both ends of a Tcr element have not been successful, ends of a cryptic element (XBU4422) were cloned previously and shown to be homologous to the ends of Tcr elements. We have obtained DNA sequences of junction regions between XBU4422 and its target from several different insertions. Comparison of junction sequences with target sequences showed that no target site duplication occurred during insertion and that XBU4422 carried 4 to 5 bp of adjacent chromosomal DNA when it excised from the chromosome and inserted in a plasmid. We identified a short region of sequence similarity between one of the ends of XBU4422 and its target site that may be important for insertion. This sequence contained an 8-bp segment that was identical to the recombinational hot spot sequence on Tn21. XBU4422 could exise itself from plasmids into which it inserted. In most cases, the excision left a single additional A behind in the target site, but precise excision was seen in one case. PMID- 1309517 TI - High-molecular-weight linear multimer formation by single-stranded DNA plasmids in Escherichia coli. AB - We inserted foreign DNA segments into plasmids which replicate by a rolling circle mechanism in Escherichia coli and observed the appearance of high molecular-weight plasmid multimers (HMW). This phenomenon, which occurs more frequently with GC-rich segments, depends on the mode of replication of the plasmid and on host homologous recombination functions. We found that (i) HMW are formed upon insertion of a foreign DNA segment into a single-stranded DNA plasmid, whereas the same DNA insert has no such effect on a theta replicon, and (ii) HMW are not present in a recA mutant strain but are found in a lexA (Ind-) mutant. Enzymatic studies allowed us to define the HMW structure as linear double stranded tandem head-to-tail plasmid repeats. Use of heteroplasmid strains showed that HMW production by one plasmid does not affect another resident plasmid, indicating that no host functions are phenotypically inactivated. This distinguishes our system from the HMW observed with various replicons in the absence of RecBCD enzyme activity. We propose that the role of the foreign insert is to protect the DNA from RecBCD exonuclease attack. PMID- 1309518 TI - The pgpA and pgpB genes of Escherichia coli are not essential: evidence for a third phosphatidylglycerophosphate phosphatase. AB - To further define the genes and gene products responsible for the in vivo conversion of phosphatidylglycerophosphate to phosphatidylglycerol in Escherichia coli, we disrupted two genes (pgpA and pgpB) which had previously been shown to encode gene products which carried out this reaction in vitro (T. Icho and C. R. H. Raetz, J. Bacteriol. 153:722-730, 1983). Strains with either gene or both genes disrupted had the same properties as the original mutants isolated with mutations in these genes, i.e., reduced in vitro phospholipid phosphatase activities, normal growth properties, and an increase in the level of phosphatidylglycerophosphate (1.6% versus less than 0.1% in wild-type strains). These results demonstrate that these genes are not required for either normal cell growth or the biosynthesis of phosphatidylglycerol in vivo. In addition, the total phosphatidylglycerophosphate phosphatase activity in the doubly disrupted mutant was reduced by only 50%, which indicates that there is at least one other gene that encodes such an activity and thus accounts for the lack of a dramatic effect on the biosynthesis of anionic phospholipids in these mutant strains. The phosphatidic acid and lysophosphatidic acid phosphatase activities of the pgpB gene product were also significantly reduced in gene-interrupted mutants, but the detection of residual phosphatase activities in these mutants indicated that additional genes encoding such phosphatases exist. The lack of a significant phenotype resulting from disruption of the pgpA and pgpB genes indicates that these genes may be required only for nonessential cell function and leaves the biosynthesis of phosphatidylglycerophosphate as the only step in E. coli phospholipid biosynthesis for which a gene locus has not been identified. PMID- 1309519 TI - A method for constructing single-copy lac fusions in Salmonella typhimurium and its application to the hemA-prfA operon. AB - This report describes a set of Escherichia coli and Salmonella typhimurium strains that permits the reversible transfer of lac fusions between a plasmid and either bacterial chromosome. The system relies on homologous recombination in an E. coli recD host for transfer from plasmid to chromosome. This E. coli strain carries the S. typhimurium put operon inserted into trp, and the resulting fusions are of the form trp::put::[Kanr-X-lac], where X is the promoter or gene fragment under study. The put homology flanks the lac fusion segment, so that fusions can be transduced into S. typhimurium, replacing the resident put operon. Subsequent transduction into an S. typhimurium strain with a large chromosomal deletion covering put allows selection for recombinants that inherit the fusion on a plasmid. A transposable version of the put operon was constructed and used to direct lac fusions to novel locations, including the F plasmid and the ara locus. Transductional crosses between strains with fusions bearing different segments of the hemA-prfA operon were used to determine the contribution of the hemA promoter region to expression of the prfA gene and other genes downstream of hemA in S. typhimurium. PMID- 1309521 TI - A directional, high-frequency chromosomal mobilization system for genetic mapping of Rhizobium meliloti. AB - A system for mapping of the Rhizobium meliloti chromosome that utilizes transposon Tn5-Mob, which carries the mobilization site of IncP plasmid RP4 (R. Simon, Mol. Gen. Genet. 196:413-420, 1984), was developed. Insertions of Tn5-Mob that were located at particular sites on the R. meliloti chromosome were isolated and served as origins of high-frequency chromosomal transfer when IncP tra functions were provided in trans. This approach is, in principle, applicable to any gram-negative bacterium in which Tn5 can transpose and into which IncP plasmids can conjugate. PMID- 1309520 TI - Mutational analysis of Agrobacterium tumefaciens virD2: tyrosine 29 is essential for endonuclease activity. AB - Agrobacterium tumefaciens VirD2 polypeptide, in the presence of VirD1, catalyzes a site- and strand-specific nicking reaction at the T-DNA border sequences. VirD2 is found tightly attached to the 5' end of the nicked DNA. The protein-DNA complex is presumably formed via a tyrosine residue of VirD2 (F. Durrenberger, A. Crameri, B. Hohn, and Z. Koukolikova-Nicola, Proc. Natl. Acad. Sci. USA 86:9154 9158, 1989). A mutational approach was used to study whether a tyrosine residue(s) of VirD2 is required for its activity. By site-specific mutagenesis, a tyrosine (Y) residue at position 29, 68, 99, 119, 121, 160, or 195 of the octopine Ti plasmid pTiA6 VirD2 was altered to phenylalanine (F). The Y-29-F or Y 121-F mutation completely abolished nicking activity of VirD2 in vivo in Escherichia coli. Two other substitutions, Y-68-F and Y-160-F, drastically reduced VirD2 activity. A substitution at position 99, 119, or 195 had no effect on VirD2 activity. Additional mutagenesis experiments showed that at position 29, no other amino acid could substitute for tyrosine without destroying VirD2 activity. At position 121, only a tryptophan (W) residue could be substituted. This, however, yielded a mutant protein with significantly reduced VirD2 activity. The nicked DNA from strains bearing a Y-68-F, Y-99-F, Y-119-F, Y-160-F, Y-195-F, or Y-121-W mutation in VirD2 was always found to contain a tightly linked protein. PMID- 1309522 TI - Broad-specificity endoribonucleases and mRNA degradation in Escherichia coli. AB - Crude extracts from Escherichia coli were screened for any broad-specificity endoribonuclease after the cell proteins were fractionated by size. In a mutant lacking the gene for RNase I (molecular mass, 27,156 Da), the only such activities were also in the size range of 23 to 28 kDa. Fractionation by chromatography on a strong cation-exchange resin revealed only two activities. One of them eluted at a salt concentration expected for RNase M and had the specificity of RNase M. It preferred pyrimidine-adenosine bonds, could not degrade purine homopolymers, and had a molecular mass of approximately 27 kDa (V. J. Cannistraro and D. Kennell, Eur. J. Biochem. 181:363-370, 1989). A second fraction, eluting at a higher salt concentration, was active against any phosphodiester bond but was about 100 times less active than are RNase I and RNase I* (a form of RNase I) in the wild-type cell. On the basis of sizing-gel chromatography, this enzyme had a molecular mass of approximately 24 kDa. We call it RNase R (for residual). RNase R is not an abnormal product of the mutant rna gene; a cell carrying many copies of that gene on a plasmid did not synthesize more RNase R. Our search for broad-specificity endoribonucleases was prompted by the expectation that the primary activities for mRNA degradation are expressed by a relatively small number of broad-specificity RNases. If correct, the results suggest that the endoribonucleases for this major metabolic activity reside in the 24- to 28-kDa size range. Endoribonucleases with much greater specificity must have as primary functions the processing of specific RNA molecules at a very limited number of sites as steps in their biosynthesis. In exceptional cases, these endoribonucleases inactivate a specific message that has such a site, and they can also effect total mRNA metabolism indirectly by a global disturbance of the cell physiology. It is suggested that a distinction be made between these processing and degradative activities. PMID- 1309523 TI - Iron uptake and molecular recognition in Pseudomonas putida: receptor mapping with ferrichrome and its biomimetic analogs. AB - The presence of an Fe(3+)-ferrichrome uptake system in fluorescent Pseudomonas spp. was demonstrated, and its structural requirements were mapped in Pseudomonas putida with the help of biomimetic ferrichrome analogs. Growth tests, 55Fe3+ uptake, and competition experiments demonstrated that the synthetic L-alanine derivative B5 inhibits the action of ferrichrome but does not facilitate Fe3+ transport, while the enantiomeric D-Ala derivative B6 fails to compete with ferrichrome. Contraction of the molecule's envelope by replacing L-Ala by glycine provided a synthetic carrier, B9, which fully simulates ferrichrome as a growth promoter. Sodium azide inhibited 55Fe3+ uptake of the Gly derivative B9, suggesting an active transport process. These data demonstrate the chiral discrimination of the ferrichrome receptor and its sensitivity to subtle structural changes. They further confirm that receptor binding is a necessary but not sufficient condition for Fe3+ uptake to occur and suggest that binding to the receptor and transport proteins might rely on different recognition patterns. PMID- 1309524 TI - Characterization of the Streptococcus adjacens group antigen structure. AB - Serological classification of bacteria requires the presence of an antigen unique to the organism of interest. Streptococci are serologically differentiated by group antigens, many of which are carbohydrates, although some are amphiphiles. This report describes the chemical characterization of the Streptococcus adjacens group antigen structure. Previous studies demonstrated that the amphiphile contained phosphorus, ribitol, galactose, galactosamine, alanine, and fatty acids. Phosphodiester bonds present in the purified group antigen were identified as part of a poly(ribitol phosphate), since ribitol phosphate was the only organic phosphate detected after acid hydrolysis. Hydrofluoric acid cleavage of the phosphodiester bonds generated oligosaccharide repeating units. Gas chromatography-mass spectrometric analysis of the methylated, acetylated oligosaccharide suggested that the repeating unit is a trisaccharide of Galp beta 1-3Galp beta 1-4GalNac with N-acetylgalactosamine attached in beta-linkage to either the number two or the number four carbon of ribitol. The lipid- and carbohydrate-substituted poly(ribitol phosphate) of the S. adjacens group antigen therefore is a unique amphiphile structure, differing in its repeating-unit structure from the polyglycerophosphate structure of the more common gram positive amphiphile lipoteichoic acid. PMID- 1309525 TI - Construction and application of plasmid- and transposon-based promoter-probe vectors for Streptomyces spp. that employ a Vibrio harveyi luciferase reporter cassette. AB - Several versatile promoter-probe vectors have been constructed for Streptomyces strains which utilize the production of blue-green light as a measure of transcription activity. Three plasmid vectors (two high and one low copy number) and two transposons are described. The multicopy plasmids pRS1106 and pRS1108 contain a transcription terminator and multiple-cloning polylinker upstream of promoterless luciferase (lux) and neomycin resistance reporter genes. Plasmid pHI90 is similar in structure to the pRS vectors except that its single copy number is an advantage for regulation studies or situations in which overexpression is otherwise toxic to the cell. The two transposons carry a promoterless lux cassette cloned such that transposition into a target DNA and fusion to the target's transcription unit occur simultaneously. Tn5351 was created by inserting the luciferase genes near the right end of the viomycin resistance transposon Tn4563. Tn5353 carries the luciferase genes near the right end of a neomycin resistance transposon derived from Tn4556. The size of Tn5353 was minimized by deleting nonessential transposon sequences, making this element small enough to be cloned into phi C31 bacteriophages for efficient transposon delivery to target cells of Streptomyces strains. The two Tnlux transposons have been used to generate Streptomyces coelicolor morphological mutants and to monitor transcription from chromosomal promoters during development. PMID- 1309526 TI - Roles of the orlA, tsE, and bimG genes of Aspergillus nidulans in chitin synthesis. AB - Strains of Aspergillus nidulans carrying the orlA1 or tse6 allele are deficient in cell wall chitin and undergo lysis at restrictive temperatures. The strains are remediable by osmotic stabilizers or by the presence of N-acetylglucosamine (GlcNAc) in the medium. The remediation by GlcNAc suggests that the lesion(s) in chitin synthesis resides in the amino sugar biosynthetic pathway prior to the synthesis of N-acetylglucosamine-6-phosphate. orlA1 strains grown at permissive temperature exhibit an abnormally low specific activity for L-glutamine:fructose 6-phosphate amidotransferase (EC 2.6.1.16, amidotransferase), the first enzyme unique to amino sugar synthesis. In addition, the enzyme produced is temperature sensitive in vitro. tsE6 strains grown at permissive temperature show virtually no amidotransferase activity. This finding is consistent with an extremely labile enzyme which is destroyed by cell breakage and extract preparation. The enzyme must be active in vivo at permissive temperatures since GlcNAc is not required for growth. Thus, two structural genes (orlA and tsE) are necessary for the amidotransferase activity. bimG11 strains are temperature sensitive for a type 1 protein phosphatase involved in cell cycle regulation and arrest in mitosis. Like orlA1 and tsE6 strains, conidia from bimG11 strains swell excessively when germinated and lyse; the germlings produced are deficient in chitin content. The amidotransferase from wild-type and mutant strains is sensitive to feedback inhibition by uridine diphosphate-N-acetylglucosamine. The sensitivity of the amidotransferase from bimG11 strains is dependent on growth temperature, while that from wild-type strains is independent of temperature. The enzyme can be desensitized in vitro under conditions consistent with a protein phosphatase reaction. It is proposed that amino sugar (and chitin biosynthesis) is partially regulated by phosphorylation-dephosphorylation of the amidotransferase or a protein regulator of the enzyme. PMID- 1309527 TI - Involvement of Fis protein in replication of the Escherichia coli chromosome. AB - We report evidence indicating that Fis protein plays a role in initiation of replication at oriC in vivo. At high temperatures, fis null mutants form filamentous cells, show aberrant nucleoid segregation, and are unable to form single colonies. DNA synthesis is inhibited in these fis mutant strains following upshift to 44 degrees C. The pattern of DNA synthesis inhibition upon temperature upshift and the requirement for RNA synthesis, but not protein synthesis, for resumed DNA synthesis upon downshift to 32 degrees C indicate that synthesis is affected in the initiation phase. fis mutations act synergistically with gyrB alleles known to affect initiation. oriC-dependent plasmids are poorly established and maintained in fis mutant strains. Finally, purified Fis protein interacts in vitro with sites in oriC. These interactions could be involved in mediating the effect of Fis on DNA synthesis in vivo. PMID- 1309528 TI - The oriT region of the conjugative transfer system of plasmid pCU1 and specificity between it and the mob region of other N tra plasmids. AB - The oriT region of the conjugative IncN plasmid pCU1 has been localized to a 669 bp sequence extending from pCU1 coordinates 8.48 to 9.15 kb. The nucleotide sequence of this region was determined. The region is AT-rich (69% AT residues), with one 19-bp and one 81-bp sequence containing 79% or more AT residues. Prominent sequence features include one set of thirteen 11-bp direct repeats, a second set of two 14-bp direct repeats, six different inverted repeat sequences ranging from 6 to 10 bp in size, and two sequences showing 12 of 13 nucleotides identical to the consensus integration host factor binding sequence. Specificity between this oriT and mobilization (mob) functions encoded by the N tra system was demonstrated. This specificity is encoded by the region lying clockwise of the BglII site at coordinate 3.3 on the pCU1 map. Two N tra plasmids isolated in the preantibiotic era were unable to mobilize recombinant plasmids carrying the oriT region of pCU1 or to complement transposon Tn5 mutations in the mob region of the closely related plasmid pKM101. PMID- 1309529 TI - Identification of the gene (aroK) encoding shikimic acid kinase I of Escherichia coli. AB - DNA sequence analysis has revealed that an unidentified open reading frame (ufr1) is present immediately preceding the aroB gene of Escherichia coli. The predicted protein product of urf1 contains a consensus ATP-binding-site sequence and shows 34% amino acid homology to shikimate kinase II in a 97-amino-acid region. Inactivation of urf1 by insertion of an antibiotic resistance gene had a polar effect on aroB, indicating that these two genes constitute a transcriptional unit. The auxotrophic requirements of a strain mutant for both urf1 and aroL (encoding shikimate kinase II) are consistent with shikimate kinase deficiency. We propose that urf1 encodes shikimate kinase I and that it be designated aroK. PMID- 1309530 TI - CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase, which is involved in the synthesis of the major wall teichoic acid in Bacillus subtilis 168, is encoded by tagF (rodC). AB - Assays of CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase (CGPTase) (EC 2.7.8.12) in membranes isolated from Bacillus subtilis 168 wild type and 11 strains bearing conditional lethal thermosensitive mutations in tagB, tagD, or tagF revealed that CGPTase deficiency was associated only with mutant tagF alleles. In vitro, thermosensitivity of CGPTase strongly suggests that the structural gene for this enzyme is tagF. We discuss apparent discrepancies between biochemical evidence favoring a membrane location for TagF and a previous report that suggested a cytoplasmic location based on sequence analysis. PMID- 1309531 TI - Heterogeneity of c-myc expression in histologically similar infiltrating ductal carcinomas of the breast. AB - Anti-c-myc monoclonal antibody was used to evaluate the distribution of the c-myc protein in normal and tumor cells of infiltrating ductal carcinoma. A semi quantitative method for reporting immunohistochemical assay results (c-myc score) that enables correlations on a more quantitative basis was used in this study. HL 60 cells demonstrated the strongest nuclear staining when fixed in cold acetone (4 degrees C) for 10 min. All 24 specimens of infiltrating ductal carcinomas of the breast and 7 of 11 samples of normal breast tissues studied revealed the presence of c-myc protein. The level of expression in normal breast tissue was much lower than that in breast cancer. Heterogeneity in expression was found within individual tumors and there were substantial differences in the level of expression among different tumors. The subcellular site of staining was predominantly nuclear, occasionally nuclear and cytoplasmic in the same cell, and rarely only cytoplasmic. All four patients with tumor cells located in close proximity to the ductal basement membrane and over-expressing c-myc protein had positive lymph nodes, suggesting that these tumors are more likely to metastasize. PMID- 1309533 TI - Formation of benzo[a]pyrene-DNA adducts in blood monocytes from lung cancer patients with a familial history of lung cancer. AB - The in vitro formation of benzo[a]pyrene-DNA adducts was determined in peripheral blood monocytes of 22 lung cancer patients with at least one first-degree relative with lung cancer and compared to results obtained in 30 healthy controls. In patients, the mean (SEM) adduct formation was 2.8 (0.3) fmol/micrograms DNA as compared to 2.1 (0.1) fmol/micrograms in controls (p less than 0.05), and it was independent of age and smoking habits. These findings support the hypothesis that carcinogen-DNA adduct formation may be one factor of a constitutionally enhanced lung cancer risk. PMID- 1309532 TI - Standardized kinetic microassay to quantify differential chemosensitivity on the basis of proliferative activity. AB - Conventionally in vitro cytotoxicity assays are performed as single-end-point determinations. To compensate for the diversity of growth rates among different cell lines in this report we describe a computerized kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. As a prerequisite four human breast cancer cell lines (MDA-MB-231, MCF-7, T-47-D and ZR-75-1) were characterized with regard to oestrogen and progesterone receptor content, modal chromosome number and proliferation kinetics depending on the number of passages in culture. With prolonged time in culture for ZR-75-1 exposed to various concentrations of cisplatinum a dose-related increase in drug effect was observed. Owing to a correction of the T/C values for the initial cell mass (at the time when drug is added) a sharp distinction between cytostatic and cytocidal drug effects becomes obvious in plots of corrected T/C values versus time of incubation. The influence of the untreated control on the corrected T/C values and possible time courses of theoretical inhibition profiles (reflecting cytostatic, transient cytotoxic or cytocidal drug effects as well as development of resistance) and their relationship to the corresponding growth curves of drug treated cells are discussed. Chemosensitivity assays with diethylstilbestrol dipropionate, tamoxifen, melphalan, cisplatinum, vinblastine, Adriamycin and 5 fluorouracil prove the theoretical considerations to be true for MDA-MB-231, MCF 7, T-47-D and ZR-75-1 human breast cancer cell lines in practice. PMID- 1309534 TI - Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. AB - Endothelial cell derived relaxing factor (EDRF) mediated relaxation of blood vessels is impaired in vessels exposed to lipoproteins in vitro and in arteries of hyperlipidemic humans and animals. To investigate the mechanism by which lipoproteins impair the effects of EDRF, which is likely nitric oxide (NO) or a related molecule, we have bioassayed EDRF/NO activity by measuring its ability to increase cGMP accumulation in rat fetal lung cultured fibroblasts (RFL-6 cells). Low density lipoprotein modified by oxidation (ox-LDL) induced a concentration dependent inhibition of EDRF activity that had been released from bovine aortic endothelial cells (BAEC) stimulated with bradykinin or the calcium ionophore A23187. In addition, lipoproteins directly impaired authentic NO-induced stimulation of cGMP accumulation in the detector cells; stimulation by sodium nitroprusside was unaffected. Ox-LDL or oxidized HDL3 were highly potent in blocking NO-stimulated cGMP accumulation with EC50's of approximately 1 microgram/ml. Lipid extracted from ox-LDL blocked NO-stimulated cGMP accumulation to about the same extent as intact ox-LDL, while the protein component of ox-LDL did not inhibit the cGMP response. These results suggest that the lipid component of oxidized lipoproteins inactivate EDRF after its release from endothelial cells. PMID- 1309535 TI - P2-purinergic receptor agonists inhibit the growth of androgen-independent prostate carcinoma cells. AB - To develop a new approach to the treatment of advanced, hormone-refractory prostate cancer, the signal transductions regulating the growth of human androgen independent prostate carcinoma cell lines were studied. Agonist-stimulated Ca2+ mobilization, a critical regulatory event in other secretory cell types, was studied as a means of identifying previously undescribed plasma membrane receptors that may transduce a growth inhibitory signal. In all of the cell lines tested, P2-purinergic receptor agonists, including ATP and certain hydrolysis resistant adenine nucleotides, induced a rapid, transient increase in cytoplasmic free Ca2+ that was detectable at 50 to 100 nM ATP, was maximal at 100 microM ATP, and was inhibited approximately 50% by chelation of extracellular Ca2+. Within 8 s after addition, ATP stimulated accumulation of the polyphosphatidylinositol products inositol (1, 4, 5) trisphosphate, inositol (1, 3, 4) trisphosphate, and inositol tetrakisphosphate. In addition to stimulating phosphatidylinositol turnover and Ca2+ mobilization, ATP and hydrolysis-resistant ATP analogues induced greater than 90% inhibition of the growth of all lines tested. These data demonstrate that human androgen-independent prostate carcinoma cells express functional P2-purinergic receptors linked to phospholipase C, and that agonists of this receptor are markedly growth inhibitory, suggesting a novel therapeutic approach to this common adult neoplasm. PMID- 1309537 TI - Double pigtail cystogastric stent in the management of pancreatic pseudocyst. AB - We describe placement of a double pigtail cystogastric stent in 5 patients with pancreatic pseudocyst using real-time ultrasonography and fluoroscopy as guidance techniques. This was done as a two-step procedure. First, a transgastric drainage catheter was placed for a period of six days. All the patients continued to have high drainage output and the cyst size decreased, as seen sonographically. Simultaneous barium meal and sinogram were then done to measure the distance between the posterior gastric wall and the cyst. A polyurethane double pigtail stent of appropriate size was then introduced to achieve cystogastric drainage. The cyst resolved in all the patients by four weeks to six weeks, when the stent was removed endoscopically. There was no recurrence of pseudocyst during follow up for 6 months to 13 months. None of the patients suffered any complication. Cystogastric drainage using a double pigtail stent is an easy and safe alternative to surgical cystogastrostomy. PMID- 1309539 TI - Ultrasound guidance for biopsy of omental abnormalities. AB - We review our two-year experience with ultrasound-guided fine needle aspiration biopsy of omental pathology. Eleven patients were referred for biopsy of omental abnormalities. Biopsy was performed without complication in all cases and the aspirates were positive for malignancy in 9. The discharge diagnosis was ovarian carcinoma in 6 patients, adenocarcinoma of unknown origin in 1, lymphoma in 1, and carcinoma of the colon in 1. The technique requires the use of a linear array transducer for biopsy guidance, and is safe, rapid, and easy to perform. PMID- 1309538 TI - In vivo validation of image-directed Doppler measurement of superior mesenteric artery blood flow. AB - Image-directed Doppler measurement of superior mesenteric artery blood flow in volunteers was validated in two artificial models with either a venous or an arterial flow profile. In the "venous" model, the Doppler device overestimated the real flow velocity by 86 +/- 7%, and in the "arterial" model by 24 +/- 9%. The areas under the time-frequency curves (AUCs) from the arterial model were measured by planimetry. A correction factor of 1.47 between flow velocities calculated after planimetry and real flow was established. Correction for this factor resulted in a flow velocity of 19.5 +/- 4.7 cm/s and a blood flow rate of 377 +/- 166 ml/min in the volunteers. PMID- 1309540 TI - Echocardiographic evaluation of the valves and roots of the pulmonary artery and aorta in the developing fetus. AB - Because of the fluid-filled lungs in the fetus, the ultrasound beam can penetrate to the root of the pulmonary artery perpendicularly. Using M-mode echocardiography, the following dimensions were measured: the pulmonary and aortic valve excursion in 19 fetuses, and the pulmonary and aortic root internal diameter in 70 fetuses, between 18 and 42 weeks, menstrual age. The measured dimensions were then correlated with the biparietal diameter. The correlation coefficients for the measurements ranged from 0.873 to 0.892. Regression analysis showed that the best fit of the data was a linear model from which the 5% and 95% confidence limits were derived for individual predictions of the arterial dimensions. The ratios of the pulmonary/aortic valve excursion and the pulmonary/aortic internal diameter were approximately 1:1. These results are of potential value in the prenatal detection of great arterial valve or root diseases. PMID- 1309536 TI - Strategies for the identification of icosahedral virus receptors. PMID- 1309541 TI - Clinical versus ultrasound examination of the thyroid gland in common clinical practice. AB - In a prospective series of 72 patients, clinical and ultrasonographic examination of the thyroid gland were compared in detail. Normal-sized lobes were differentiated from enlarged ones both by inspection and by palpation. When lobar size was assessed by palpation, the estimate was most clearly influenced by increase in width. The correlation between two examiners in lobe size assessment was significant. In the classification of thyroid disease as diffuse, solitary, or multinodular, clinical examination and ultrasonography correlated significantly. However, only one third of the clinically solitary nodules proved to be solitary by ultrasound examination. Of 77 separate nodules, 43 escaped detection on clinical examination. Of these 43, 14 nodules exceeded 2 cm in diameter. It is concluded that the use of ultrasonography frequently alters the primary evaluation of thyroid nodularity based on palpation. PMID- 1309542 TI - Ophthalmic and cerebral blood flow velocities in preterm infants: influence of ambient lighting conditions. AB - Doppler ultrasound was used to study ophthalmic and middle cerebral artery flow velocities at different ambient lighting conditions in 28 preterm infants in the first week of life. We found significant increases of ophthalmic and middle cerebral artery blood flow velocities when ambient light was increased from moderate to intense. Flow velocities in the ophthalmic artery increased significantly more than in the middle cerebral artery. Doppler ultrasound studies of ophthalmic blood flow velocity may assist in answering the intriguing question whether light-induced changes of ocular perfusion play a role in the development of retinopathy of prematurity. PMID- 1309543 TI - The subxyphoid view: a method to evaluate the right lower lobe sonographically. PMID- 1309544 TI - Intratesticular masses associated with abnormally functioning adrenal glands. PMID- 1309545 TI - Gastric lymphoma: ultrasound appearance due to isolated mucosal infiltration. PMID- 1309546 TI - Antenatal detection of hydranencephaly at 12 weeks, menstrual age. PMID- 1309548 TI - First trimester sonographic diagnosis of diprosopus twins with craniorachischisis. PMID- 1309547 TI - Cystic mesothelioma of the retroperitoneum. PMID- 1309549 TI - Cystic leiomyosarcoma of the stomach in a child. PMID- 1309550 TI - Prenatal ultrasound diagnosis of complete absence of the lumbar spine and sacrum. PMID- 1309551 TI - Pelvic varices simulating bilateral adnexal masses: differential diagnosis by transvaginal color Doppler. PMID- 1309552 TI - Isolated hydrocolpos: ultrasound findings and the importance of confident preoperative diagnosis. PMID- 1309553 TI - Hepatocellular carcinoma presenting only as portal venous tumor thrombosis: CT demonstration. AB - We describe two cases of hepatocellular carcinoma initially presenting with portal vein tumor thrombi but with no demonstrable tumor in the liver parenchyma outside the portal vein. Both patients had cirrhosis of the liver and had tumor thrombi in the main portal vein and its branches. The tumor thrombi were demonstrated on ultrasonography, CT, angiography as expanding intraluminal masses. PMID- 1309554 TI - Sequential CT in monitoring experimental lung transplant. AB - The criteria for diagnosis of lung rejection remain controversial. In this study early changes in lung rejection were characterized using sequential CT with the aim of developing a sensitive and safe monitoring method, which would also provide specific information on graft status. Twenty-one experimental single lung transplants (SLTs) in piglets, including unmodified rejections, immunosuppressed recipients, and autogenic reimplants, were scanned using CT on days 3, 5, 7, 10, 14, 22 up to 134 days after operation. In addition to morphological analysis, bilateral densitometric CT measurements of the peripheral lung parenchyma were used to evaluate the intensity of interstitial infiltration of lung grafts. Altogether 67 postoperative CT studies were carried out. Simultaneous transbronchial/thoracic biopsies were undertaken. The mean follow-up time was 28 days (range 0-134 days). The experience obtained was then used in relation to SLT in a male patient for chronic obstructive pulmonary disease. All piglets had a typical hilar reimplantation response, which disappeared in 10-20 days. Two distinct patterns of radiological acute rejection were found. Increasing peripheral alveolar infiltrates reflected early massive rejection in untreated animals. In immunosuppressed animals, after the initial reimplantation response, acute rejection was detected as densitometrically measured diffuse interstitial infiltration over the whole graft. Local findings, like focal infections, were seen later in the lingula and basal portions of the graft. In the SLT patient, density changes preceded clinical rejection episodes, which responded to steroid therapy. In the experimental study, the lung graft was compared to normal contralateral lung. In the SLT patient, however, this was not possible, and, therefore, the subsequent repeated CT studies formed the basis of clinical follow up. Sequential imaging and densitometric measurements allowed objective estimation of diffuse interstitial infiltration relating to rejection. PMID- 1309555 TI - Immunohistochemical localization of rat submandibular gland esterase B (homologous to the RSKG-7 kallikrein gene) in relation to other serine proteases of the kallikrein family. AB - The rat submandibular gland contains several members of the kallikrein family. In the present study we purified and raised an antiserum against one of these enzymes, i.e., esterase B, which was first described by Khullar et al. in 1986. N terminal amino acid analysis revealed complete homology between esterase B and the kallikrein family gene RSKG-7. For characterization of the antiserum, flat bed isoelectrofocusing with immunoblotting was superior to immunoelectrophoresis and double immunodiffusion in detecting and identifying crossreacting proteins. This was due to the fact that kallikrein-like enzymes were readily separated by isoelectrofocusing, and immunoreactivity was easily detected by the sensitive peroxidase-anti-peroxidase staining after blotting onto nitrocellulose membrane. Immunohistochemical controls were carried out accordingly, including homologous as well as crossreacting antigens. In the submandibular gland, esterase B was detected exclusively in all granular convoluted tubular cells, co-localized with tissue kallikrein and tonin. Some staining was also observed in striated duct cells; however, this staining reaction was induced by cross-reactivity with kallikrein, since staining was abolished by addition of kallikrein as well as esterase B to the primary antiserum. It was therefore concluded that like tonin and antigen gamma, but unlike kallikrein, esterase B was not detected in the striated ducts of the submandibular, parotid, or sublingual glands. This separation in anatomic distribution between esterase B and kallikrein may indicate that prokallikrein activation is not the only biological function of esterase B. PMID- 1309556 TI - Studies of CD4- CD8- alpha beta bone marrow T cells with suppressor activity. AB - The predominant T cell subset in the bone marrow of specific pathogen-free C57BL/Ka and BALB/c mice expressed the alpha beta+ TCR CD4- CD8- surface phenotype. Purified C57BL/Ka alpha beta+ TCR CD4- CD8- marrow cells obtained by cell sorting suppressed the MLR of C57BL/Ka responder and BALB/c stimulator spleen cells. Although the percentage of typical T cells in the spleen was markedly reduced in adult nude mice or normal neonatal mice as compared to the normal adult, the percentage of alpha beta+ TCR CD4- CD8- cells in the spleen and marrow was not. The percentage of "self-reactive" V beta 5+ T cells in the BALB/c spleen was markedly reduced as compared to that in the C57BL/Ka spleen. However, the percentages in the bone marrow were similar. The results indicate that the predominant subset of marrow T cells in these pathogen-free mice differ with regard to surface marker phenotype, function, dependence on the adult thymus, and deletion of certain self-reactive V beta receptors as compared to typical spleen T cells. The marrow T cells appear to develop directly from marrow precursors without rearranged beta chain genes during a 48 hour in vitro culture. PMID- 1309557 TI - Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1/IL-8. AB - To test the hypothesis that mesothelial cells play a role in regulating inflammatory responses within the pleural space, we examined neutrophil chemotactic activity released by cytokine-stimulated mesothelial cells. Human mesothelial cells were isolated from patients with transudative pleural effusions and cultured. The purity of the cell population was assessed by morphologic, immunocytochemical, and biochemical characteristics. Confluent fourth passage mesothelial cell plates were exposed to varying concentrations of the recombinant human cytokines IL-1 alpha, TNF-alpha, or IFN-gamma, or Escherichia coli endotoxin (LPS). Polymorphonuclear neutrophil (PMN) chemotactic activity in the conditioned media was measured in microchemotaxis chambers. Although none of the cytokines demonstrated inherent chemotactic activity, each stimulated mesothelial cells to produce PMN chemotactic activity in a dose-dependent manner. TNF-alpha stimulated the release of the greatest quantity, whereas stimulation with IFN gamma and IL-1 alpha resulted in the release of lesser but still significant quantities of PMN chemotactic activity. By contrast, LPS did not increase the basal level of chemotactic activity produced by the cells. The cytokine-induced chemotactic activity was proteinaceous, required de novo synthesis, and had a predominant m.w. of 10,000. Significant quantities of immunoreactive neutrophil activating peptide-1 (NAP-1)/IL-8 were detected in mesothelial cell supernatants after stimulation with each of the cytokines. The neutrophil chemotactic activity of supernatants from mesothelial cells stimulated with either IL-1 alpha or IFN gamma was completely neutralized with rabbit anti-human NAP-1/IL-8 polyclonal antiserum. The same antiserum neutralized the majority, but not all, of the neutrophil chemotactic activity in supernatants from TNF-stimulated mesothelial cells. Stimulated mesothelial cells also expressed an inducible mRNA transcript that hybridized with a specific oligonucleotide probe for human NAP-1/IL-8. These observations provide a mechanism whereby mesothelial cells could respond to inflammatory stimuli in the underlying lung and regulate inflammatory responses within the pleural space. PMID- 1309558 TI - The binding subunit of pertussis toxin inhibits IL-1 induction of IL-2 and prostaglandin production. AB - The inhibitory effect of pertussis toxin on the action of IL-1 has been investigated. The toxin inhibited IL-1-induced production of IL-2 mRNA and protein in EL4 cells. The B oligomer of the toxin, which was shown to be devoid of ADP-ribosylating activity, proved as inhibitory as the holotoxin. The inhibition was therefore attributable to the binding subunit of the toxin and not to its ability to ADP-ribosylate G proteins. The toxin did not affect the IL-1R binding to its ligand, nor did it inhibit an early post-receptor event, the induction of the transcription factor NF kappa B. This implied that the toxin was not uncoupling IL-1R signaling. The toxin, or its B oligomer, inhibited PGE2 synthesis in human gingival fibroblasts stimulated by IL-1, but not by PMA. Assay of PG synthetic activity in the cells after addition of exogenous arachidonic acid suggested impairment by the toxin of induction of PG-synthesizing enzymes. IL-1 stimulation of IL-6 or collagenase production by fibroblasts was unaffected by pertussis toxin. The binding subunit of the toxin inhibits certain IL-1 responses by virtue of previously unrecognized actions on lymphoid and fibroblastic cells. It does not appear to block early signaling and the inhibition highly unlikely to involve inactivation of a G protein. PMID- 1309559 TI - Transforming growth factor-beta in synovial fluids modulates Fc gamma RII (CD16) expression on mononuclear phagocytes. AB - Mononuclear phagocytes in the synovium of patients with arthritis, in contrast to blood monocytes, were found to express a third receptor for the constant region of Ig (Fc gamma RIII), in addition to Fc gamma RI and Fc gamma RII. Previously identified on mature mononuclear phagocytes or phagocytes exposed to transforming growth factor-beta (TGF-beta) in vitro, this study documents the presence of Fc gamma RIII (CD16) expressing cells at an inflammatory site. Furthermore, the presence of CD16 on the majority of the LeuM3 (CD14) positive synovial monocytic cells could be mimicked by exposing blood monocytes to synovial fluids from patients with rheumatoid arthritis (17 of 19) and synovial fluids from patients with osteoarthritis (4 of 4). In additional studies, the soluble factor in inflammatory synovial fluids responsible for regulating CD16 expression was found to be consistent with the presence of TGF-beta. Inhibition of the activity in synovial fluids with a neutralizing antibody to TGF-beta confirmed a role for this peptide in synovial phagocytic cell CD16 expression. Moreover, signal transduction through CD16 on synovial phagocytes resulted in augmented extracellular release of superoxide anion that may contribute to tissue damage and other inflammatory sequelae. Identification of TGF-beta and its association with upregulation of CD16 at sites of chronic inflammation may provide insight into the destructive lesions associated with inflammatory arthropathies. PMID- 1309561 TI - Expression of platelet-derived growth factor-beta receptors on human fibroblasts. Regulation by recombinant platelet-derived growth factor-BB, IL-1, and tumor necrosis factor-alpha. AB - Stimulation of human fibroblasts by platelet-derived growth factor (PDGF)-BB leads to a down-regulation of PDGF beta-receptors and a concomitant appearance of intracellular granular accumulations of receptors, as determined by stainings with the mAb PDGFR-B2. The granules contained both the ligand and PDGF beta receptors, as revealed by double-immunofluorescence staining, and were formed in response to PDGF-BB but not in response to other cytokines tested. The formation of intracellular PDGF beta-receptor granules was dependent on PDGF-BB concentration and time of stimulation. The granular PDGF beta-receptor staining on cells treated with PDGF-BB for 1 h at 37 degrees C was used to investigate the effects of macrophage-derived cytokines on PDGF beta-receptor expression. The number of PDGF beta-receptor granules was found to be reduced in fibroblasts grown for 48 h in the presence of PDGF-BB, TNF-alpha, or IL-1; PDGF-AA under the same conditions had no effect. The reduction observed was paralleled by a decrease in cell surface expression of PDGF beta-receptors, measured as binding of 125I-PDGF-BB and of the PDGFR-B2 antibody. Furthermore, both TNF-alpha and IL 1 decreased the detergent-extractable pool of PDGF-beta receptors in the fibroblasts, as revealed by immunoblotting of detergent cell extracts. Finally, the decrease in PDGF beta-receptors after culturing of the cells in the presence of TNF-alpha and IL-1 was accompanied by a decreased incorporation of [3H]thymidine in response to PDGF-BB stimulation. In conclusion, our data suggest that certain macrophage-derived cytokines can modulate the expression of PDGF beta-receptors by cultured fibroblasts, which may contribute in part to their reduced responsiveness to PDGF. PMID- 1309560 TI - The mechanism of internalization of platelet-activating factor in activated human neutrophils. Enhanced transbilayer movement across the plasma membrane. AB - Recent studies suggest that cellular internalization of platelet-activating factor (PAF), a potent ether phospholipid mediator of inflammation, is modulated by, as yet undefined cellular mechanisms. Using an albumin extraction method, the internalization of PAF and several PAF analogues was studied in the resting and stimulated human neutrophil. Our data demonstrate that internalization of these analogues is largely dependent on the state of cellular activation and that the process is not specific for certain unique structural features of the PAF molecule including the 1-position ether linkage, 2-position acetyl substitution, or choline polar head group. Furthermore, the internalization process was shown not to be dependent on the PAF receptor, metabolism of the molecule, or the process of endocytosis. Data are presented to suggest that the route of internalization of PAF is enhanced transbilayer movement (flipping) across the plasma membrane occurring as a result of changes in membrane physical properties accompanying cellular activation. It is proposed that in addition to enhanced internalization of PAF, modulation of PAF biosynthesis and net release from the stimulated neutrophil may be consequences of enhanced transbilayer movement of PAF across the activated plasma membrane. PMID- 1309562 TI - Heterogeneity in the allosteric interaction between the gamma-aminobutyric acid (GABA) binding site and three different benzodiazepine binding sites of the GABAA/benzodiazepine receptor complex in the rat nervous system. AB - In the present communication we have investigated the allosteric coupling between the gamma-aminobutyric acidA (GABAA) receptor and the pharmacologically different benzodiazepine (BZD) receptor subtypes in membranes from various rat nervous system regions. Two types of BZD receptors (type I and type II) have been classically defined using CL 218.872. However, using zolpidem, three different BZD receptors have been identified by binding displacement experiments in membranes. These BZD receptor subtypes displayed high, low, and very low affinity for zolpidem. The distribution of the high- and low-affinity binding sites for zolpidem was similar to that of type I and type II subtypes in cerebellum, prefrontal cortex, and adult cerebral cortex. On the other hand, the very-low affinity binding site was localized in relative high proportion in spinal cord, hippocampus, and newborn cerebral cortex and, to a minor extent, in superior colliculus. The allosteric coupling between the GABAA receptor and the BZD receptor subtypes was different. The high- and low-affinity binding sites for zolpidem seemed to have a similar high degree of coupling, except in spinal cord. On the other hand, the very-low-affinity binding site for zolpidem displayed a low degree of coupling with the GABAA receptor. These results seem to indicate that the different efficacy of GABA in enhancing the [3H]flunitrazepam binding could be due to the different BZD receptor subtypes present in the GABAA/BZD receptor complex and, moreover, led us to speculate that the low GABA efficacy found in membranes from spinal cord, hippocampus, and newborn cerebral cortex might be due to the presence in relatively high proportion of the very-low affinity binding site for zolpidem. PMID- 1309563 TI - Phosphorylation of the MARCKS protein (P87), a major protein kinase C substrate, is not an obligatory step in the mitogenic signaling pathway of basic fibroblast growth factor in rat oligodendrocytes. AB - Basic fibroblast growth factor (bFGF) is a well-characterized peptide hormone that has mitogenic activity for various cell types and elicits a characteristic set of responses on the cell types investigated. In this report we confirmed that bFGF is a potent mitogen for rat brain-derived oligodendrocyte (OL) precursor cells as well as for differentiated OL in secondary culture. bFGF was shown to induce expression of the protooncogene c-fos in OL. The role of protein kinase C (PKC) in mediating bFGF-stimulated proliferation as well as c-fos expression in OL was investigated. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated c-fos expression but did not trigger cell proliferation. When PKC was down-regulated by pretreatment of OL with PMA for 20 h, the bFGF-mediated stimulations of OL proliferation and c-fos mRNA expression were still observed, whereas the induction of c-fos mRNA by PMA was totally inhibited. These data demonstrate that the bFGF mitogenic signaling pathway in OLs does not require PKC. On the other hand, bFGF was found to stimulate specifically the phosphorylation of a limited number of PKC substrates in oligodendroglial cells, including the MARCKS protein. The bFGF-dependent phosphorylation of MARCKS protein was totally inhibited when PKC was first down-regulated, indicating that the phosphorylation of this protein is PKC dependent. Tryptic digestion of the phosphorylated MARCKS protein revealed that bFGF stimulated specifically the phosphorylation of the MARCKS protein on a single phosphopeptide. We provide evidence that bFGF also stimulated fatty acylation of the MARCKS protein, which might explain the observed specific bFGF-dependent phosphorylation of this protein in OL. We propose that bFGF-dependent fatty acylation and phosphorylation of the MARCKS protein are not essential for the transduction of the bFGF mitogenic signal but are probably linked to differentiation processes elicited by bFGF on OL. PMID- 1309564 TI - Biochemical responses mediated by N-methyl-D-aspartate receptors in rat cortical slices are differentially sensitive to magnesium. AB - The effects of magnesium on the inhibition of phosphoinositide (PI) hydrolysis and the stimulation of [3H]norepinephrine release by N-methyl-D-aspartate (NMDA) in rat cortical slices were investigated. Removal of the magnesium from the buffer resulted in a small reduction of the inhibitory effect of 100 microM NMDA (34% inhibition in the absence of magnesium, compared with 51% for the control) when slices were coincubated with NMDA and carbachol. Addition of 10 mM Mg2+ also allowed the inhibitory effect of 100 microM NMDA on carbachol-stimulated PI hydrolysis to be expressed (44% inhibition) under these conditions. Concentration effect curve analysis for the NMDA-induced inhibition of carbachol-stimulated PI hydrolysis indicated that the IC50 for NMDA was decreased from 14.9 microM for the control to 4.2 microM in the absence of magnesium. The absence of magnesium also had small effects on the concentration-effect curve for (+)-5-methyl-10,11 dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate reversal of the inhibitory effects of NMDA on carbachol-stimulated PI hydrolysis. The absence of magnesium also shifted slightly downward and flattened the NMDA concentration effect curve if the cortical slices were pretreated with NMDA in the presence or absence of magnesium followed by removal of the NMDA and subsequent stimulation with carbachol. In contrast, cortical slices that had been prepared and treated similarly to the slices used in the PI experiments were very sensitive to the inhibitory effects of magnesium when using the NMDA stimulation of [3H]norepinephrine release assay in the presence or absence of carbachol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309566 TI - Characterization of solubilized opioid receptors: reconstitution and uncoupling of guanine nucleotide-sensitive agonist binding. AB - Opioid receptors were solubilized from bovine striatal membranes with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). High concentrations of NaCl (0.5-1.0 M) were necessary to ensure optimal yields, which ranged from 40 to 50% of membrane-bound receptors. This requirement was found to be specific for sodium, with only lithium able to substitute partially, as previously reported for solubilization with digitonin. Opioid antagonists, but not agonists, were able to bind to soluble receptors with high affinity. High-affinity binding of mu, delta, and kappa agonists was reconstituted following polyethylene glycol precipitation and resuspension of CHAPS extract. Evidence is presented suggesting that this is the result of inclusion of receptors in liposomes. Competition and saturation studies indicate that the three opioid receptor types retain their selectivity and that they exist in the reconstituted CHAPS extract in a ratio (50:15:35) identical to that in the membranes. In reconstituted CHAPS extract, as in membranes, mu-agonist binding was found to be coupled to a guanine nucleotide binding protein (G protein), as demonstrated by the sensitivity of [3H][D-Ala2,N-methyl-Phe4,Gly5-ol]-enkephalin ([3H]DAGO) binding to guanosine 5'-O-(thiotriphosphate) (GTP gamma S). In the reconstituted CHAPS extract, complete and irreversible uncoupling by GTP gamma S was observed, whereas membrane-bound receptors were uncoupled only partially. Treatment with GTP gamma S, at concentrations that uncoupled the mu receptors almost completely, resulted in a fourfold decrease in the Bmax of [3H]DAGO binding with a relatively small change in the KD. Competition experiments showed that the Ki of DAGO against [3H]bremazocine was increased 200-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309565 TI - Alterations in the gamma-aminobutyric acid-gated chloride channel following transient forebrain ischemia in the gerbil. AB - The role of inhibitory neurotransmission in selective neuronal degeneration after transient forebrain ischemia was studied by binding of t [35S]butylbicyclophosphorothionate ([35S]TBPS) to the gamma-aminobutyric acid (GABA)-gated chloride channel and measurement of GABAA receptor function in Mongolian gerbil brain. [35S]TBPS binding to the hippocampus, striatum, and cortex quantified by autoradiography and muscimol-stimulated 36Cl- uptake in synaptoneurosomes of the same regions were examined 1, 4, and 29 days after a 5 min bilateral carotid occlusion. [35S]TBPS binding was decreased in the pyramidal cell dendritic layers, stratum oriens, and stratum lacunosum-moleculare of the CA1 hippocampus, 4 and 29 days after occlusion, and in the stratum radiatum 29 days after occlusion. [35S]TBPS binding sites in the lateral striatum decreased 47% 4 days after occlusion. At the same time, there was a corresponding decrease in muscimol-stimulated 36Cl- uptake in the striatal synaptoneurosomes. Muscimol stimulated 36Cl- uptake in the hippocampus decreased slightly 4 days after occlusion and more so after 29 days, although these decreases were not significant. No changes were observed in somatosensory cortex at any time point. These data suggest that a portion of GABAA receptors in areas sensitive to ischemic insult are associated with degenerating neurons, whereas other GABAA) receptors are spared. PMID- 1309567 TI - Endothelin receptors on cultured fetal rat diencephalic glia. AB - The recently described family of proteins, the endothelins, are produced in neurons and bind to extravascular sites in the CNS. To characterize these receptors, we carried out studies on cultures of fetal rat diencephalic glia. Scatchard analysis of saturation binding studies was done for astrocytes (greater than 95% glial fibrillary acidic protein positive). For endothelin 3 (ET-3) and ET-1, respectively, a single receptor class of KD 0.41 +/- 0.05 and 0.62 +/- 0.04 nM and a receptor density of 42 +/- 0.8 and 58 +/- 1.1 fmol/mg of glial protein was found. Bound and cross-linked 125I-ET-3 or ET-1 showed a single predominant receptor band at Mr 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis; a minor band at 50,000 was also seen. At concentrations equal to the receptor KD, the major brain form of ET, ET-3, stimulated a nearly 200% increase in the incorporation of tritiated thymidine into glia. ET-3 and ET-1 significantly impaired the ability of atrial natriuretic peptide (ANP) to generate cyclic GMP, and isoproterenol to generate cyclic AMP. The ability of ET to inhibit ANP-induced cyclic GMP generation was reversed by cycloheximide and actinomycin-D, whereas the inhibition of isoproterenol-induced cyclic AMP generation was partially and significantly blocked by inhibitors of calcium influx, protein kinase C action, or G protein activation, as well. Astrocytes from this part of the brain are a potential target cell for endothelin, assuming these findings are present in vivo. This neuropeptide may serve as a growth stimulator for astrocytes and modulator of the actions of catecholamines or ANP on glia by inhibiting second messenger generation. PMID- 1309568 TI - Effects of dopaminergic transmission interruption on the D2 receptor isoforms in various cerebral tissues. AB - We examined the effects of an interruption of dopamine neurotransmission, by either dopamine receptor blockade or degeneration of dopamine neurons by 6 hydroxydopamine, on the levels of D2 receptor mRNAs. In addition, we evaluated by the polymerase chain reaction (PCR) the relative abundance of the two D2 receptor isoform mRNAs generated by alternative splicing. Daily injections of 4 mg/kg of haloperidol to rats elicited in striatum a rapid and progressive increase in D2 receptor mRNA levels, which reached 70% after a 15-day treatment. By contrast, there was no apparent change in D2 receptor mRNA levels in cerebral cortex and pons-medulla, in spite of an increased density of D2 receptor in the former tissue. Using the PCR with primers flanking the alternative exon, we observed that the relative proportion of the shorter receptor isoform (D2S) mRNA was slightly but significantly enhanced in cerebral cortex (17%) and pons-medulla (18%) after a 15-day haloperidol treatment. Unilateral degeneration of dopamine neurons induced by local injection of 6-hydroxydopamine resulted in a marked decrease in levels of total D2 receptor mRNAs in substantia nigra (-79%) and ventral tegmental (-63%) area, two cell body areas. In the substantia nigra, the longer isoform (D2L) mRNA was significantly more decreased in content than the D2S isoform mRNA, so that there was a large enhancement in the relative abundance of the latter (81%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309569 TI - 6-Methylmercaptopurine riboside is a potent and selective inhibitor of nerve growth factor-activated protein kinase N. AB - Protein kinase N (PKN) is a soluble, apparently novel serine protein kinase that is activated by nerve growth factor (NGF) and other agents in PC12 pheochromocytoma cells as well as in several nonneuronal cell lines. Purine analogs, such as 6-thioguanine and 2-aminopurine, have been found to inhibit PKN in vitro. When applied to intact cells, these compounds suppress certain biological responses to NGF, but not others, a findings suggesting the presence of multiple pathways in the NGF mechanism. We report here that 6 methylmercaptopurine riboside (6-MMPR) inhibits NGF-stimulated PKN activity in vitro with an apparent Ki of approximately 5 nM. This is approximately 1,000-fold lower than the Ki of the most potent purine inhibitor of PKN. Compounds similar to 6-MMPR, but lacking the methyl or riboside groups, were much less potent as PKN inhibitors. A survey of six additional purified protein kinases shows no inhibitory effect of 6-MMPR, thus indicating a good degree of specificity of this compound for PKN. In contrast to NGF-stimulated PKN, a PKN-like activity stimulated in PC12 cells in response to activation of cyclic AMP-dependent protein kinase was nearly insensitive to 6-MMPR. Application of 6-MMPR to intact PC12 cells resulted in blockade of several responses to NGF (neurite regeneration and ornithine decarboxylase induction) but not of several others (rapid enhancement of tyrosine hydroxylase phosphorylation and PKN activation). These findings suggest that 6-MMPR is a potent and selective agent for characterizing PKN in vitro and for assessing its potential role in the multiple pathways of the NGF mechanism of action. PMID- 1309570 TI - Quisqualate-stimulated phosphatidylinositol breakdown in rat cerebellar membranes. AB - The effect of quisqualate, an excitatory amino acid agonist, on the breakdown of exogenously added phosphatidylinositol was investigated in a membrane preparation from the cerebellum of young rats. Quisqualate stimulated phospholipase C activity in a dose-dependent manner in the presence of guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S). Half-maximal activation of the quisqualate response required 0.15 microM GTP gamma S and was optimal at a free Ca2+ concentration of 300 nM. Phosphoinositide breakdown was also stimulated by quisqualate using either exogenous phosphatidylinositides 4,5-bisphosphate or endogenous labeled phosphoinositides as the substrate for phospholipase C in cerebellar membranes. In the presence of guanine nucleotides, other excitatory amino acid agonists, such as L-glutamate, trans-D,L-1-aminocyclopentyl-1,3 dicarboxylic acid, and ibotenate, but not N-methyl-D-aspartate, stimulated phosphatidylinositol breakdown. However, quisqualate displayed the highest response among these excitatory amino acid agonists. These data indicate that there is a direct activation of phosphoinositide-specific phospholipase C by excitatory amino acids through a process dependent on the presence of guanine nucleotides. PMID- 1309571 TI - 4-aminopyridine-induced epileptiform activity and a GABA-mediated long-lasting depolarization in the rat hippocampus. AB - Two types of spontaneous filed potentials were recorded in rat hippocampal slices after addition of 4-aminopyridine (4-AP; 50 microM). One consisted of brief, epileptiform discharges that occurred at 0.6 +/- 0.2 sec-1 in the CA3 and CA1 areas. The other type occurred less frequently (0.036 +/- 0.013 sec-1) and was recorded in CA1, CA3, and dentate areas. It corresponded in all regions to an intracellular long-lasting depolarization (LLD; duration, 300-1200 msec; peak amplitude, 2-15 mV) that was abolished by bicuculline methiodide; therefore, it was mediated by GABAA receptors. Sectioning experiments and the occurrence of propagation failures indicated that LLDs could be initiated by any area of the slice. Furthermore, the propagation of LLDs did not follow any consistent or predictable pattern along known anatomical hippocampal pathways. Finally, neither the occurrence nor the propagation of LLDs was affected when excitatory synaptic transmission was blocked by NMDA and non-NMDA receptor antagonists. In the presence of antagonists of glutamatergic receptors, LLDs disappeared after the omission of Ca2+ or the addition of Cd2+ to the perfusing solution, suggesting that synaptic transmission was required for their generation. These data indicate that 4-AP discloses both interictal epileptiform discharges and LLDs in the rat hippocampus. The first type of activity is presumably related to certain properties of CA3 pyramidal neurons and the neuronal circuit, whereas LLDs originate from the spontaneous, periodic activity of GABAergic interneurons located in any area of the hippocampus, and can propagate to the other areas by the use of nonsynaptic mechanisms. We propose that 4-AP reveals a novel type of interaction among GABAergic interneurons that is based on the accumulation and the dispersion of K+. PMID- 1309572 TI - Partial glycinergic denervation induces transient changes in the distribution of a glycine receptor-associated protein in a central neuron. AB - The effect of partial glycinergic denervation on the cellular distribution of the 93 kDa peripheral polypeptide associated with the glycine receptor was studied at the level of the teleost Mauthner cell, an identified neuron of the goldfish brain (Carassius auratus). Previous studies using monoclonal antibodies raised against purified glycine receptors and immunoperoxidase staining have shown that these proteins are localized in clusters on the entire surface of this neuron. Specifically, the 93 kDa polypeptide was situated only on the cytoplasmic side of the postsynaptic membrane facing active zones. Unilateral electrolytic lesions of the vestibular complex caused the degeneration of some glycinergic afferents to this neuron. When the first signs of this response appeared, 3 d after the surgery, there was also a change in the ultrastructural distribution of the 93 kDa polypeptide in the deafferented cell. The synaptic protein apposed to degenerating axons did not spread onto adjacent extrasynaptic membranes, and it disappeared a few hours after the disruption of its presynaptic element. At the same time, a cytoplasmic immunoreactivity appeared as randomly distributed clusters in the deafferented Mauthner cell; these aggregates, not seen in control preparations, were never found inside membrane-bound organelles. In some preparations these clusters were localized along arrays at a relatively constant distance from the plasma membrane. The intracellular immunoreaction product was found in the soma and the initial part of the dendrites, gradually decreasing in number and intensity toward the extremities of these processes. At later postoperative stages, 10-15 d after surgery, the 93 kDa immunoreactivity remained only at postsynaptic membranes facing intact terminals. Similar alterations following denervation were observed in reticular neurons, at the level at which degenerating presynaptic terminals were also detected. In contrast, continuous 3 d blockade of synaptic transmission by strychnine, an antagonist of the glycine receptor, had no effect on either the distribution of the surface receptor clusters, or the 93 kDa peripheral protein linked to these receptors. Taken together, our results suggest that the ultrastructural distribution of the glycine receptor complex is regulated by "trophic" factors rather than by transmitter-evoked synaptic activity. PMID- 1309573 TI - Cell-specific posttranslational events affect functional expression at the plasma membrane but not tetrodotoxin sensitivity of the rat brain IIA sodium channel alpha-subunit expressed in mammalian cells. AB - The rat brain IIA Na+ channel alpha-subunit was expressed and studied in mammalian cells. Cells were infected with a recombinant vaccinia virus (VV) carrying the bacteriophage T7 RNA polymerase gene and were transfected with cDNA encoding the IIA Na+ channel alpha-subunit under control of a T7 promoter. Whole cell patch-clamp recording showed that functional IIA channels were expressed efficiently (approximately 10 channels/microns2 in approximately 60% of cells) in Chinese hamster ovary (CHO) cells and in neonatal rat ventricular myocytes but were expressed poorly in undifferentiated BC3H1 cells and failed to express in Ltk- cells. However, voltage-dependent Drosophila Shaker H4 K+ channels and Escherichia coli beta-galactosidase were expressed efficiently in all four cell types with VV vectors. Because RNA synthesis probably occurs without major differences in the cytoplasm of all infected cell types under the control of the T7 promoter and T7 polymerase, we conclude that cell type-specific expression of the Na+ channel probably reflects differences at posttranslational steps. The gating properties of the IIA Na+ currents expressed in cardiac myocytes differed from those expressed in CHO cells; most noticeably, the IIA Na+ currents displayed more rapid macroscopic inactivation when expressed in cardiac myocytes. These differences also suggest cell-specific posttranslational modifications. IIA channels were blocked by approximately 90% by 90 nM TTX when expressed either in CHO cells or in cardiac myocytes; the latter also continued to display endogenous TTX-resistant Na+ currents. Therefore, the TTX binding site of the channel is not affected by cell-specific modifications and is encoded by the primary amino acid sequence. PMID- 1309574 TI - Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus. AB - The functional properties, ionic basis, and possible convergence and interaction of postsynaptic actions mediated by muscarinic and alpha 1-adrenergic receptors were examined in cat and guinea pig dorsal lateral geniculate (LGNd) neurons maintained in thalamic slices in vitro. The possible involvement of GTP-binding proteins was also examined. Extracellular recordings from cat LGNd revealed the presence of two subpopulations of neurons. The most prevalent generated rhythmic high-frequency (300-500 Hz) bursts of two to six action potentials each, with an interburst frequency of 1-3 Hz. Intracellular recordings revealed that this activity is typical of thalamocortical relay cells in the apparent absence of neuromodulatory input. Application of ACh or noradrenaline (NA) to rhythmically oscillating neurons in the cat LGNd resulted in cessation of this activity followed by the appearance of single spike firing. Intracellular recordings revealed that this change in firing mode was associated with a depolarization of the neuron out of the range of intrinsic rhythmic oscillation and into or near the single spike firing mode. The voltage characteristics of the current underlying the cholinergic and noradrenergic slow depolarization were investigated in guinea pig LGNd neurons. Application of the muscarinic agonist acetyl-beta-methylcholine (MCh) to presumed relay neurons resulted in a hyperpolarization due to the activation of an outward K+ current. This response was followed by a slow depolarization due to reduction of a relatively non voltage-dependent potassium current distinct from IM and IAHP. Application of NA resulted in a slow depolarization that was also associated with reduction of this relatively linear K+ current. The MCh- and NA-induced slow depolarizations displayed the property of occlusion, indicating convergence of action. However, these responses were mediated by pharmacologically distinct receptors since the MCh-induced reduction in K+ current was blocked by scopolamine while that induced by NA was blocked by the alpha 1-adrenoceptor antagonist prazosin. Intracellular diffusion of GTP-gamma-S resulted in the inward current responses to NA and MCh being irreversible, suggesting the possible involvement of a G-protein. Prior exposure to pertussis toxin did not affect the inward current response to NA and MCh, while the outward K+ current responses induced by application of MCh or the GABAB agonist baclofen were blocked. These results reveal that activation of muscarinic or alpha 1-adrenergic postsynaptic receptors in the LGNd result in a shift in firing mode from rhythmic oscillation to tonic single spike activity through a decrease in a relatively linear K+ current mediated through a pertussis toxin-insensitive G-protein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309575 TI - Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection. AB - Basic fibroblast growth factor (bFGF) is a potent trophic factor for neurons and astrocytes and recently has been implicated in the pathology of Alzheimer's disease. In order to better understand the role of bFGF in normal brain function and during pathology, we have analyzed its anatomical distribution and its response to injury in the CNS. Double-staining immunohistochemistry showed that bFGF immunoreactivity was localized in astrocytes, in select neuronal populations, and occasionally in microglial cells throughout the normal rat brain. Neuronal populations that showed bFGF immunoreactivity included septohippocampal nucleus, cingulate cortex, subfield CA2 of the hippocampus, cerebellar Purkinje cells, cerebellar deep nuclei, facial nerve nucleus, and the motor and spinal subdivisions of the trigeminal nucleus and facial nerve nucleus. The pattern of bFGF immunoreactivity in the hippocampus was examined following entorhinal cortex lesion, or fimbria-fornix transection. After entorhinal cortex lesion, bFGF immunoreactivity increased in the outer molecular layer of the dentate gyrus ipsilateral to the lesion. The lesion effect on bFGF immunoreactivity was expressed as an increase in the number of bFGF astrocytes, as an increase in the intensity of bFGF immunoreactivity within astrocytes, and as an increase of bFGF immunoreactivity in the surrounding extracellular matrix, relative to the contralateral side. The time course and pattern of reorganization paralleled the sprouting of septal cholinergic terminals in response to the same type of lesion, suggesting that bFGF may play an important role in lesion-induced plasticity. After transection of the fimbria-fornix, chronic infusion of bFGF appeared to preserve NGF receptors on neurons within the medial septal complex and, as previously reported, prevent the death of medial septal neurons. Therefore, it appears that bFGF infusion, which has been shown to increase the synthesis of NGF by astrocytes (Yoshida and Gage, 1991), also helps enable neurons to respond to NGF. This suggests that after injury bFGF may participate in a cascade of neurotrophic events, directly and indirectly facilitating neuronal repair and/or promoting neuronal survival. PMID- 1309576 TI - Pre- and postsynaptic inhibition by opioids in rat striatum. AB - The physiological role of opioid peptides in the rat striatum was sought by intracellular recording in vitro. Excitatory synaptic potentials (mediated by glutamate or aspartate) and inhibitory synaptic potentials (mediated by GABA) were isolated pharmacologically and/or by positioning the stimulation electrode over the external capsule. Opioid agonists and antagonists selective for mu-, delta-, and kappa-receptors were applied by superfusion. Two main actions of opioids were observed. First, mu- and delta-selective opioids presynaptically inhibited the excitatory postsynaptic potential, whereas only delta-selective opioids decreased the inhibitory synaptic potential. Second, a small subpopulation of cells (not medium spiny neurons) were hyperpolarized by delta selective agonists. The results indicate that the main action of opioids on striatal neurons is presynaptic inhibition of the corticostriate excitatory synaptic input. PMID- 1309577 TI - Evidence for prenatal competition among the central arbors of trigeminal primary afferent neurons. AB - Previous studies have shown that damage to vibrissa follicles in newborn rats and mice does not alter the brainstem representations of the remaining vibrissa as demonstrated by staining for mitochondrial enzymes such as cytochrome oxidase (CO) succinic dehydrogenase. This study asked whether this lack of effect might be due to the fact that the trigeminal primary afferents in rodents are already quite well developed at birth. We assessed this possibility by using CO staining the evaluate patterns in the brainstems of pre- and postnatal rats. A vibrissa related pattern began to emerge in trigeminal nucleus principalis and subnucleus interpolaris (Spl) by embryonic day (E-) 19 and appeared fully developed by the day of birth (P-0). We also made partial lesions of the vibrissa pad on E-15-20 and on P-0, killed pups on P-5-7, and measured the size of the CO-stained patches in Spl on both sides of the brainstem. The correspondence between CO patches and clusters of primary afferent terminal arbors was verified in some animals by combining transganglionic horseradish peroxidase tracing and CO staining. Vibrissa pad damage on E-15-18 resulted in significant (20.1-36.9%) increases in the average area of the remaining CO patches in Spl ipsilateral to the lesion. Vibrissa pad damage on E-19, E-20, and P-0 produced small (6.2-8.9%), but insignificant, increases in patch size in Spl ipsilateral to the lesion. We used anatomical and electrophysiological methods to determine whether our lesions altered the trigeminal innervation of surviving vibrissa follicles. We recorded single trigeminal ganglion cells from 12 rats that sustained vibrissa pad lesion on E-17. As in normal rats, all of the 49 vibrissa-sensitive ganglion cells isolated in the lesioned animals were responsive to deflection of one and only one vibrissa. We also dissected 11 deep vibrissal nerves from intact follicles in adult rats that sustained fetal vibrissa pad damage on E-17, and counted numbers of myelinated axons in 1 microns plastic sections. These data were compared with counts from corresponding follicles on the intact side of the face. The average number of myelinated axons innervating follicles in the damaged vibrissa pads was 196.8 +/- 27.9, and that for the corresponding contralateral nerves was 194.6 +/- 25.7. These data suggest that competitive interactions among the central arbors of trigeminal primary afferents in fetal life may influence the development of central vibrissa representations and, further, that lesion-induced central changes need not be correlated with alterations in the peripheral innervation of undamaged follicles. PMID- 1309578 TI - Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. AB - In ischemic and in inflamed tissues, pH levels down to 5.4 have been measured, and this local acidosis may contribute to pain and hyperalgesia in disease states. To evaluate the role of acid pH in nociception, we have studied identified primary afferents in a rat skin-saphenous nerve preparation in vitro where the receptive fields can be superfused at the highly permeable corium side with controlled solutions. The nerve endings were exposed to CO2-saturated synthetic interstitial fluid (SIF;pH 6.1) and to carbogen-gassed SIF phosphate buffered to different acid pH levels (5 min duration, 10 min intervals). Mechanical thresholds were repeatedly tested in a "blind" fashion by von Frey hair stimulation. Low-threshold mechanosensitive A beta- (n = 12) and A delta fibers (n = 11) were not excited or sensitized by acid pH levels. In 24 of 96 nociceptor type C- and A delta-fibers, irregular low-frequency discharge with poor response characteristics was induced. However, a distinct subpopulation of mechanoheat sensitive, "polymodal" C-units (n = 25; 38%) showed stimulus-related responses increasing with proton concentration and encoding the time course of the pH change. Threshold levels were found to range from pH 6.9 to 6.1; mean maximum discharge was at pH 5.2. All such fibers responded to CO2 as well as to phosphate-buffered solution at the same pH 6.1. The CO2 responses, however, displayed significantly shorter latencies and more pronounced dynamic phases. The carboanhydrase blocker acetazolamide markedly delayed and reduced the CO2 responses. Prolonged application of acid pH (30 min) evoked nonadapting activity irrespective of oxygen supply. Many, but certainly not all, fibers sensitive to protons were also driven by capsaicin (10(-6) M, 10(-5) M) and vice versa. Repeated or prolonged treatment with low pH induced a significant and lasting decrease of the mechanical (von Frey) thresholds in almost all C-fibers tested (from 35 to 16 mN, on average), and this occurred whether or not a fiber was excited by protons. The sensitizing effect was more pronounced the higher the initial von Frey thresholds (0.75 rank correlation). This sensitization to mechanical stimulation was in contrast to the combined action of other inflammatory mediators, bradykinin, 5-HT, histamine and prostaglandin E2. In conclusion, we suggest that pH sensitivity of nociceptors may be an important source of pain and hyperalgesia. PMID- 1309579 TI - Wheat bran and corn oil do not influence proliferation in the colon of healthy rats when energy intakes are equivalent. AB - Dietary intakes of fiber (wheat bran) and fat (corn oil) by rats were quantitatively varied for 6 wk while intakes of energy and essential nutrients were constant among the diets. The influence of wheat bran and corn oil levels on colonic epithelial cell proliferation was assessed using [3H]thymidine incorporation assays. Cellular proliferation in the cecum, proximal colon and distal colon was not significantly higher when healthy rats consumed low fiber in comparison to high fiber diets, nor when healthy rats consumed high fat diets in comparison to low fat diets. Additionally, there were no significant interactions between these variables. In comparison to the low fiber diets, diets high in fiber caused a significantly lower pH of luminal contents of the cecum and distal colon, but there were no significant differences in the total short-chain fatty acid concentrations of cecal digesta. These results suggest that when energy intakes are equivalent among diets, low levels of fiber or high levels of fat in the diet do not cause biological changes in colonic mucosa that may be associated with increased risk of colonic cancer. PMID- 1309580 TI - Re: The necessity of contralateral surgical exploration in Wilms tumor with modern noninvasive imaging technique: a reassessment. PMID- 1309581 TI - Human papillomavirus types 16 and 18 are not involved in human prostate carcinogenesis: analysis of archival human prostate cancer specimens by differential polymerase chain reaction. AB - Human papilloma viruses (HPV) have been implicated in the pathogenesis of a variety of malignancies, especially in carcinomas of the female genital tract. Recently, based on observations using the polymerase chain reaction amplification assay, HPV types 16 and 18 specific DNA sequences have been detected in prostate cancer specimens obtained by transurethral resection. Since HPV types 16 and 18 have been shown to possess oncogenic potential, an association between HPV infection and prostatic carcinoma has been suggested. In order to exclude potentially HPV-colonized urethral mucosa from analysis and restrict our study to predominantly malignant tissue, cancerous areas from a series of 30 paraffin embedded prostate adenocarcinomas were microdissected and analyzed for the presence of HPV 16 or HPV 18 specific sequences by a modification of PCR (D-PCR) and Southern blot analysis. Despite the high sensitivity of our analytical technique, we found no evidence of HPV-DNA of either type in any of the 30 primary prostate cancers. In contrast, both HPV 16 (2/8 specimens) and HPV 18 (2/8 specimens) DNA was detected in randomly chosen cervical carcinomas using the D-PCR methodology. Our data would indicate that the oncogenic HPV-types 16 and 18 are unlikely effectors of prostate carcinogenesis. PMID- 1309582 TI - 'Alter' a virus molecularly for polio vaccine? PMID- 1309583 TI - From the Alcohol, Drug Abuse, and Mental Health Administration. PMID- 1309584 TI - Estrogen replacement therapy after breast cancer. PMID- 1309585 TI - Case-mix groups for VA hospital-based home care. AB - The purpose of this study is to group hospital-based home care (HBHC) patients homogeneously by their characteristics with respect to cost of care to develop alternative case mix methods for management and reimbursement (allocation) purposes. Six Veterans Affairs (VA) HBHC programs in Fiscal Year (FY) 1986 that maximized patient, program, and regional variation were selected, all of which agreed to participate. All HBHC patients active in each program on October 1, 1987, in addition to all new admissions through September 30, 1988 (FY88), comprised the sample of 874 unique patients. Statistical methods include the use of classification and regression trees (CART software: Statistical Software; Lafayette, CA), analysis of variance, and multiple linear regression techniques. The resulting algorithm is a three-factor model that explains 20% of the cost variance (R2 = 20%, with a cross validation R2 of 12%). Similar classifications such as the RUG-II, which is utilized for VA nursing home and intermediate care, the VA outpatient resource allocation model, and the RUG-HHC, utilized in some states for reimbursing home health care in the private sector, explained less of the cost variance and, therefore, are less adequate for VA home care resource allocation. PMID- 1309586 TI - Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. AB - Histological and anatomopathological studies performed on 152 independent myeloblastosis-associated virus type 1 (MAV1)-induced nephroblastomas allowed us to precisely define the chronology of tumor development in chickens. Three tumors representing increasing developmental stages were used to construct genomic libraries and to study both the state of proviral genomes and the sites of MAV1 integration in genomic DNA. We established that increasing levels of proviral rearrangement, eventually leading to the elimination of infectious MAV genomes, were associated with tumor progression and that 22 individual tumors, representative of different developmental stages, did not contain any common MAV1 integration site. Cloning of cellular fragments flanking the MAV1-related proviruses in tumor DNA showed that each one of eight nephroblastomas tested expressed a high level of an as yet unidentified cellular gene (nov) whose transcription is normally arrested in adult kidney cells. Cloning of the normal nov gene established that in one tumor, fused long terminal repeat-truncated nov mRNA species were expressed, indicating that at least in that case, the high level of nov expression was under the control of the MAV long terminal repeat promoter. The normal nov gene encodes a putative 32-kDa secreted polypeptide, which is a member of a new family of proteins likely to be involved in cell growth regulation. We also showed that the expression of an amino-terminal truncated nov product in chicken embryo fibroblasts was sufficient to induce their transformation. PMID- 1309587 TI - The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells. AB - Regulation of replicative functions in the Epstein-Barr virus (EBV) genome is mediated through activation of a virally encoded transcription factor, Z (BZLF1). We have shown that the Z gene product, which binds to AP-1 sites as a homodimer and has sequence similarity to c-Fos, can efficiently activate the EBV early promoter, BMRF1, in certain cell types (i.e., HeLa cells) but not others (i.e., Jurkat cells). Here we demonstrate that the c-myb proto-oncogene product, which is itself a DNA-binding protein and transcriptional transactivator, can interact synergistically with Z in activating the BMRF1 promoter in Jurkat cells (a T-cell line) or Raji cells (an EBV-positive B-cell), whereas the c-myb gene product by itself has little effect. The simian virus 40 early promoter is also synergistically activated by the Z/c-myb combination. Synergistic transactivation of the BMRF1 promoter by the Z/c-myb combination appears to involve direct binding by the Z protein but not the c-myb protein. A 30-bp sequence in the BMRF1 promoter which contains a Z binding site (a consensus AP-1 site) is sufficient to transfer high-level lymphoid-specific responsiveness to the Z/c-myb combination to a heterologous promoter. That the c-myb oncogene product can interact synergistically with an EBV-encoded member of the leucine zipper protein family suggests c-myb is likely to engage in similar interactions with cellularly encoded transcription factors. PMID- 1309588 TI - Oncogenes result in genomic alterations that activate a transcriptionally silent, dominantly selectable reporter gene (neo). AB - Although oncogenes and tumor suppressor genes have been implicated in carcinogenesis and tumor progression, their relationship to the development of genomic instability has not been elucidated. To examine this role, we transfected oncogenes (polyomavirus middle [Py] and large T [MT and LT]) and adenovirus serotype 5 E1A) into two NIH 3T3-derived cell lines, EN/NIH 2-4 and EN/NIH 2-20. Both cell lines contain two stable integrants of a variant of the retrovirus vector pZipNeoSV(x)1 that has been modified by deletion of the enhancer elements from the long terminal repeats. DNA rearrangements activating the silent neomycin phosphotransferase gene (neo) present in these integrants were identified by selection of cells in the antibiotic G418. Whereas control-transfected EN/NIH cell lines do not yield G418-resistant subclones (GRSs), a fraction of oncogene transfected EN/NIH 2-4 (8 of 19 Py MT, 5 of 17 Py LT, and 11 of 19 E1A) and 2-20 (7 of 15 Py MT) cell lines gave rise to GRSs at differing frequencies (0.33 x 10( 6) to 46 x 10(-6) for line 2-4 versus 0.11 x 10(-6) to 1.3 x 10(-6) for line 2 20) independent of cell generation time. In contrast, a distinctly smaller fraction of mutant Py MT-transfected EN/NIH cell lines (1 of 10 MT23, 1 of 10 MT1015, and 0 of 10 MT59b) resulted in GRSs. Southern analysis of DNA from selected oncogene-transfected GRSs demonstrated genomic rearrangements of neo containing cellular DNA that varied in type (amplification and/or novel fragments) and frequency depending on the specific oncogene and EN/NIH cell line used in transfection. Furthermore, only one of the two neo-containing genomic loci present in both EN/NIH cell lines appeared to be involved in these genomic events. In addition to effects related to the genomic locus, these observations support a role for oncogenes in the development of genetic changes associated with tumor progression. PMID- 1309589 TI - Structure of DRE, a retrotransposable element which integrates with position specificity upstream of Dictyostelium discoideum tRNA genes. AB - Different Dictyostelium discoideum strains contain between 2 and 200 copies of a retrotransposable element termed DRE (Dictyostelium repetitive element). From the analysis of more than 50 elements, it can be concluded that DRE elements always occur 50 +/- 3 nucleotides upstream of tRNA genes. All analyzed clones contain DRE in a constant orientation relative to the tRNA gene, implying orientation specificity as well as position specificity. DRE contains two open reading frames which are flanked by nonidentical terminal repeats. Long terminal repeats (LTRs) are composed of three distinct modules, called A, B, and C. The tRNA gene proximal LTR is characterized by one or multiple A modules followed by a single B module (AnB). With respect to the distal LTR, two different subforms of DRE have been isolated. The majority of isolated clones contains a distal LTR composed of a B module followed by a C module (BC), whereas the distal LTR of the other subform contains a consecutive array of a B module, a C module, a slightly altered A module, another B module, and another C module (BC.ABC). Full-length as well as smaller transcripts from DRE elements have been detected, but in comparison with the high copy number in D. discoideum strains derived from the wild-type strain NC4, transcription is rather poor. PMID- 1309590 TI - Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. AB - Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation. PMID- 1309591 TI - The basic region of myogenin cooperates with two transcription activation domains to induce muscle-specific transcription. AB - Myogenin is a skeletal muscle-specific transcription factor that can activate myogenesis when introduced into a variety of nonmuscle cell types. Activation of the myogenic program by myogenin is dependent on its binding to a DNA sequence known as an E box, which is associated with numerous muscle-specific genes. Myogenin shares homology with MyoD and other myogenic regulatory factors within a basic region and a helix-loop-helix (HLH) motif that mediate DNA binding and dimerization, respectively. Here we show that the basic region-HLH motif of myogenin alone lacks transcriptional activity and is dependent on domains in the amino and carboxyl termini to activate transcription. Analysis of these N- and C terminal domains through creation of chimeras with the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that they act as strong transcriptional activators. These transcription activation domains are dependent for activity on a specific amino acid sequence within the basic region, referred to as the myogenic recognition motif (MRM), when an E box is the target for DNA binding. However, the activation domains function independent of the MRM when DNA binding is mediated through a heterologous DNA-binding domain. The activation domain of the acidic coactivator VP16 can substitute for the myogenin activation domains and restore strong myogenic activity to the basic region-HLH motif. Within a myogenin-VP16 chimera, however, the VP16 activation domain also relies on the MRM for activation of the myogenic program. These findings reveal that DNA binding and transcriptional activation are separable functions, encoded by different domains of myogenin, but that the activity of the transcriptional activation domains is influenced by the DNA-binding domain. Activation of muscle specific transcription requires collaboration between the DNA-binding and activation domains of myogenin and is dependent on events in addition to DNA binding. PMID- 1309592 TI - Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals. AB - Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1. PMID- 1309593 TI - Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. AB - The long terminal repeat of Moloney murine leukemia virus (MuLV) contains the upstream conserved region (UCR). The UCR core sequence, CGCCATTTT, binds a ubiquitous nuclear factor and mediates negative regulation of MuLV promoter activity. We have isolated murine cDNA clones encoding a protein, referred to as UCRBP, that binds specifically to the UCR core sequence. Gel mobility shift assays demonstrate that the UCRBP fusion protein expressed in bacteria binds the UCR core with specificity identical to that of the UCR-binding factor in the nucleus of murine and human cells. Analysis of full-length UCRBP cDNA reveals that it has a putative zinc finger domain composed of four C2H2 zinc fingers of the GLI subgroup and an N-terminal region containing alternating charges, including a stretch of 12 histidine residues. The 2.4-kb UCRBP message is expressed in all cell lines examined (teratocarcinoma, B- and T-cell, macrophage, fibroblast, and myocyte), consistent with the ubiquitous expression of the UCR binding factor. Transient transfection of an expressible UCRBP cDNA into fibroblasts results in down-regulation of MuLV promoter activity, in agreement with previous functional analysis of the UCR. Recently three groups have independently isolated human and mouse UCRBP. These studies show that UCRBP binds to various target motifs that are distinct from the UCR motif: the adeno associated virus P5 promoter and elements in the immunoglobulin light- and heavy chain genes, as well as elements in ribosomal protein genes. These results indicate that UCRBP has unusually diverse DNA-binding specificity and as such is likely to regulate expression of many different genes. PMID- 1309594 TI - A colony-stimulating factor 1 (CSF-1) receptor/platelet-derived growth factor beta receptor gene fusion confers CSF-1 independence and tumorigenicity on a c myc-immortalized monocyte cell line. AB - Monocytes and macrophages express the receptor for the hematopoietic growth factor colony-stimulating factor 1 (CSF-1) and require this factor for growth in culture. A murine monocyte tumor cell line that lacks the usual requirement for CSF-1 was isolated. On the basis of the similarity of the structures of the CSF-1 and platelet-derived growth factor (PDGF) receptors and because monocytes normally secrete PDGF, we analyzed the tumor cell line for anomalous expression of the PDGF-R beta gene. Two different cDNAs that each contain sequences corresponding to the complete coding sequence of PDGF-R beta fused (in frame) to the amino-terminal half of the CSF-1 receptor were isolated. Introduction of these PDGF-R beta-related cDNAs into two partially transformed, CSF-1-dependent monocyte cell lines resulted in autonomous growth and cell transformation. These monocyte cell lines exhibit a novel form of growth factor receptor activation that can lead to oncogenic growth in collaboration with the c-myc oncogene. PMID- 1309595 TI - Differential splicing in the extracellular region of fibroblast growth factor receptor 1 generates receptor variants with different ligand-binding specificities. AB - We have cloned a genomic region of the murine fibroblast growth factor (FGF) receptor 1 (FGFR1) gene that includes three alternative exons for the third immunoglobulinlike domain in the extracellular region of the receptor. The mRNA of one of these splice variants encodes a secreted receptor that lacks transmembrane and cytoplasmic sequences as well as a portion of the third immunoglobulinlike domain. Highest levels of mRNA encoding this variant were found in brain, skeletal muscle, and skin. We expressed this form of FGFR1 in CHO cells and showed that the recombinant secreted protein binds acidic FGF. We also discovered a novel alternative exon in the third immunoglobulinlike domain that encodes part of a transmembrane FGFR1 mRNA. This exon is highly homologous to the corresponding region of the keratinocyte growth factor receptor. Transcripts including this exon were present at highest levels in the skin. We cloned an FGFR1 cDNA which includes this exon and expressed this receptor variant in L6 rat skeletal muscle myoblasts. The new receptor variant had a 50-fold-lower affinity for basic FGF than does the published FGFR1 variant, whereas both forms of receptor bound acidic FGF with high affinity. These results show that the third immunoglobulinlike domain plays an important role in determining the binding specificities for different FGFs. Our data provide the first evidence that differential splicing in the extracellular region of a receptor gene generates receptor variants with different ligand-binding specificities. PMID- 1309597 TI - Transmission of HCV by organ transplantation. PMID- 1309598 TI - Transmission of HCV by organ transplantation. PMID- 1309596 TI - Purification of core-binding factor, a protein that binds the conserved core site in murine leukemia virus enhancers. AB - The Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major genetic determinant of the thymic disease specificity of the Moloney virus genetically maps to two protein binding sites in the Moloney virus enhancer, the leukemia virus factor b site and the adjacent core site. Point mutations introduced into either of these sites significantly shifts the disease specificity of the Moloney virus from thymic leukemia to erythroleukemia (N. A. Speck, B. Renjifo, E. Golemis, T. Frederickson, J. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We have purified several polypeptides that bind to the core site in the Moloney virus enhancer. These proteins were purified from calf thymus nuclear extracts by selective pH denaturation, followed by chromatography on heparin-Sepharose, nonspecific double-stranded DNA-cellulose, and core oligonucleotide-coupled affinity columns. We have achieved greater than 13,000-fold purification of the core-binding factors (CBFs), with an overall yield of approximately 19%. Analysis of purified protein fractions by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis reveals more than 10 polypeptides. Each of the polypeptides was recovered from an SDS-polyacrylamide gel, and those in the molecular size range of 19 to 35 kDa were demonstrated to have core-binding activity. The purified CBFs were shown by DNase I footprint analyses to bind the core site in the Moloney virus enhancer specifically, and also to core motifs in the enhancers from a simian immunodeficiency virus, the immunoglobulin mu chain, and T-cell receptor gamma-chain genes. PMID- 1309599 TI - Polar and lateral flagellar motors of marine Vibrio are driven by different ion motive forces. AB - Various species of marine Vibrio produce two distinct types of flagella, each adapted for a different type of motility. A single, sheathed polar flagellum is suited for swimming in liquid medium, and numerous unsheathed lateral flagella, which are produced only under viscous conditions, are suited for swarming over viscous surfaces. Both types of flagella are driven by reversible motors embedded in the cytoplasmic membrane. Here we report that the energy source for the polar flagellar motor of Vibrio parahaemolyticus is the sodium-motive force, whereas the lateral flagellar motors are driven by the proton-motive force. This is evidence that two distinct types of flagella powered by different energy sources are functionally active in one cell. PMID- 1309600 TI - Scientific misconduct. NIH staffer finds warm reception on other side. PMID- 1309601 TI - Common tumors. AB - Common tumors of the hand and upper extremity are, by definition, benign conditions. There is a predictable pattern of occurrence and presentation for many of these lesions. The practitioner should always bear in mind, however, that any tumor that appears anywhere in the body can appear in the hand and upper extremity. Moreover, several of the benign conditions can, in certain clinical settings, have a predilection for transformation or association with more aggressive conditions. We would emphasize that the approach to any tumor be carefully considered and include an appropriate differential diagnosis. Any suspicious lesion should be examined thoroughly, including first-order screening tests, history, physical examination, radiographic imaging, and laboratory evaluations followed by more detailed diagnostic imaging prior to surgery. Surgery should be approached as a biopsy, with the possibility of frozen section analysis, and the possibility of a two-staged operation for tumor removal with appropriate margins if necessary. PMID- 1309603 TI - Intracellular injection of Ca2+ chelators blocks induction of long-term depression in rat visual cortex. AB - In a variety of brain structures repetitive activation of synaptic connections can lead to long-term potentiation (LTP) or long-term depression (LTD) of synaptic transmission, and these modifications are held responsible for memory formation. Here we examine the role of postsynaptic Ca2+ concentration in the induction of LTD in the neocortex. In layer III cells of the rat visual cortex, LTD can be induced by tetanic stimulation of afferent fibers ascending from the white matter. We show that LTD induction is reliably blocked by intracellular injection of either EGTA or BAPTA [bis(2-aminophenoxy)ethane-N,N,N',N' tetraacetate], two different Ca2+ chelators. This confirms that the processes underlying the induction of LTD in neocortex are located postsynaptically and indicates that they depend on intracellular Ca2+ concentration. Thus, both LTP and LTD induction appear to involve calcium-mediated processes in the postsynaptic neuron. We propose that LTD is caused by a surge of calcium either through voltage-gated Ca2+ conductances and/or by transmitter-induced release of calcium from intracellular stores. PMID- 1309602 TI - Antibody specific for the Thr-286-autophosphorylated alpha subunit of Ca2+/calmodulin-dependent protein kinase II. AB - We report the production of an antibody specific for Ca2+/calmodulin-dependent protein kinase II (CaM-KII) autophosphorylated only at Thr-286 of the alpha subunit. Peptide Y-66 [sequence MHRQETVDC (Met-281 to Cys-289 of alpha subunit of CaM-KII)] was synthesized and phosphorylated by the CaM-KII endogenous to synaptic cytoskeleton (postsynaptic density-enriched fraction); the phosphorylated amino acid residue threonine corresponds to Thr-286 in the kinase alpha subunit. The phosphorylated Y-66 peptide was separated from the unphosphorylated peptide by HPLC and used as an immunogen after being coupled to hemocyanin. The antibodies that reacted with hemocyanin and unphosphorylated Y-66 peptide were adsorbed, and then IgG was purified. ELISA proved that the IgG obtained reacted specifically with phosphorylated Y-66 peptide. Immunoblot analysis showed that the antibody reacted specifically to the autophosphorylated CaM-KII both in purified and synaptic cytoskeleton-associated form. Appearance of CaM-KII subunits immunoreactive to anti-phosphorylated Y-66 antibody paralleled the generation of Ca(2+)-independent kinase activity. Immunocytochemical experiments clearly showed expression of the Thr-286- or Thr-287 autophosphorylated form of CaM-KII in cultured hippocampal cells treated with N methyl-D-aspartate. Thus, this antibody could be extremely useful for studying the biological functions of CaM-KII. PMID- 1309604 TI - Importance of primer selection for the detection of hepatitis C virus RNA with the polymerase chain reaction assay. AB - We compared four primer sets from conserved regions of the hepatitis C virus (HCV) genome for their ability to detect HCV RNA in a "nested" cDNA polymerase chain reaction assay on sera from 114 anti-HCV antibody-positive individuals from around the world. The different primer sets had equivalent sensitivity, detecting less than 1 chimpanzee ID50 (dose that infects 50%) when tested against reference strain H of HCV. We tested equal amounts of RNA extracted from the serum of each individual with the four primer sets. The set derived from two highly conserved domains within the 5' noncoding (NC) region of the HCV genome, which also share significant similarity with Pestivirus 5' NC sequences, was the most effective at detecting HCV RNA. All samples positive for HCV RNA with any other primer set were also positive with the primer set from the 5' NC region, and the latter was at least 3 times more likely to detect HCV infection than a primer set from within the nonstructural protein 3-like gene region (P less than 0.001). We had no false positive results in greater than 500 negative controls interspersed among the test samples. The 5' NC region primer set detected HCV-specific RNA, verified by high-stringency Southern blot hybridization and DNA sequencing, in 100% of 15 acute and 33 chronic non-A, non-B hepatitis patients from the United States, Europe, and Asia and 10 hepatocellular carcinoma patients from Africa and Asia that tested negative for the hepatitis B virus-encoded surface antigen. In conclusion, use of an appropriate primer set is crucial for detecting HCV RNA in the serum of infected individuals. PMID- 1309605 TI - Targeting of hexokinase 1 to liver and hepatoma mitochondria. AB - The proportion of hexokinase (HK; EC 2.7.1.1) isozyme 1 (HK1) that is bound to the outer mitochondrial membrane is tissue specific and developmentally regulated. HK activity is known to be markedly elevated in many cancer cells and a significant fraction is mitochondrial bound. This study examined the role of the 15-amino acid N-terminal domain of HK1 in binding to liver and hepatoma mitochondria. A chimeric reporter construct, pCMVHKCAT, encoding this HK1 domain coupled to the chloramphenicol acetyltransferase (CAT) gene was electroporated into mouse Hepa 1-6 hepatoma cells. After digitonin treatment, cell fractions were assayed for HK, lactate dehydrogenase, and CAT activities. Digitonin (75 micrograms/mg of protein) caused cytosolic leak but 70% of HK remained with the pellet. HKCAT, like HK, remained predominantly with the pellet; CAT form the control, pCMVCAT, remained mostly unbound. Binding of membrane-free cell extracts to rat liver mitochondria in vitro showed 91% of the HKCAT bound, whereas only 12% of CAT bound. Specificity of HKCAT binding to mitochondria was demonstrated by competition of HK1 for HKCAT binding sites on rat liver mitochondria as well as by blockage of HKCAT binding by N,N'-dicyclohexylcarbodiimide, which covalently binds to porin and blocks HK1 binding. Deletional mutant constructs of HKCAT showed reduced binding with increasing deletion size. In summary, these studies demonstrate that the 15-amino acid N-terminal domain of HK1 is necessary and sufficient to confer mitochondrial binding properties to CAT and that there is specificity for this binding to the mitochondria. PMID- 1309606 TI - Computational model of the on-alpha ganglion cell receptive field based on bipolar cell circuitry. AB - The on-alpha ganglion cell in the area centralis of the cat retina receives approximately 450 synapses from type b1 cone bipolar cells. This bipolar type forms a closely spaced array (9 microns), which contributes from 1 to 7 synapses per b1 cell throughout the on-alpha dendritic field. Here we use a compartmental model of an on-alpha cell, based on a reconstruction from electron micrographs of serial sections, to compute the contribution of the b1 array to the on-alpha receptive field. The computation shows that, for a physiologic range of specific membrane resistance (9500-68,000 omega.cm2) and a linear synapse, inputs are equally effective at all points on the on-alpha dendritic tree. This implies that the electrotonic properties of the dendritic tree contribute very little to the domed shapes of the receptive field center and surround. Rather, these shapes arise from the domed distribution of synapses across the on-alpha dendritic field. Various sources of "jitter" in the anatomical circuit, such as variation in bipolar cell spacing and fluctuations in the number of synapses per bipolar cell, are smoothed by the overall circuit design. However, the computed center retains some minor asymmetries and lumps, due to anatomical jitter, as found in actual alpha-cell receptive fields. PMID- 1309607 TI - Patchy accumulation of apical Na+ transporters allows cross talk between extracellular space and cell nucleus. AB - Intracellular Na+ activities and local current densities were measured in fused Madin-Darby canine kidney cells using Na+ and voltage-sensing microelectrodes. Na+ that enters the cell across the apical plasma membrane accumulates initially in the nucleoplasm, several seconds ahead of its appearance in the cell cytoplasm. The spatial distribution of Na+ currents, produced by a local superfusion of the cell surface, indicates a nonuniform, patchy accumulation of apical Na+ transporters in the vicinity of the nucleus. Such pathways for direct Na+ flux between extracellular space and cell nucleus could be potentially important for gene activation. PMID- 1309608 TI - Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. AB - Expression cDNA cloning and structural analysis of the human keratinocyte growth factor receptor (KGFR) revealed identity with one of the fibroblast growth factor (FGF) receptors encoded by the bek gene (FGFR-2), except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. Genomic analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells, and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript. Thus, two growth factor receptors with different ligand-binding specificities and expression patterns are encoded by alternative transcripts of the same gene. PMID- 1309609 TI - A nuclear protein essential for binding of rat 1,25-dihydroxyvitamin D3 receptor to its response elements. AB - Recombinant 1,25-dihydroxyvitamin D3 receptor from a baculovirus expression system requires a mammalian-derived nuclear accessory protein for binding to a vitamin D response element (DRE). This was established by electrophoretic mobility shift analyses using radiolabeled DNA probes consisting of DREs from two vitamin D-responsive genes. Mammalian nuclear extract was also required for the binding of wild-type porcine vitamin D receptor to a DRE. Surprisingly, the accessory factor-dependent formation of receptor-DRE complex was independent of exogenous 1,25-dihydroxyvitamin D3. A 59- to 64-kDa accessory protein from porcine intestinal nuclear extract was identified by size-exclusion chromatography. Nuclear extracts from rat liver and kidney contained accessory factor, whereas smaller amounts were detected in heart muscle. Spleen and skeletal muscle contained no detectable accessory factor. PMID- 1309610 TI - High-resolution tandem mass spectrometry of large biomolecules. AB - Unit-resolution mass spectra have been obtained for peptides as large as 17 kDa, providing information on impurities and adduct ions, as well as accurate molecular weight values. Electrospray ionization produces many multiply-charged species of the same mass; isotopic peak resolution provides direct charge state assignment from the unit mass spacing of the isotopes. This is of special value when the spectrum also has many masses, such as from precursor ion dissociation or impurities. Mass measuring errors not only are concomitantly lower (less than 0.1 Da) than when the isotopic peaks are unresolved but also are independent of variations in 13C/12C natural isotopic abundances. Also, larger errors are avoided that occur when the measured peak envelope includes impurity or adduct ions. This also benefits tandem mass spectrometry; dissociation of peptide ions as large as 8.5 kDa yields fragment masses consistent (less than 0.1 Da) with their amino acid sequences. PMID- 1309611 TI - Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. AB - Coxsackievirus B3-induced myocarditis in different immunocompetent mouse strains was used as a model to investigate interrelationships between virus replication and development of chronic enteroviral heart disease. Using in situ hybridization to detect enteroviral RNA, we show that heart muscle infection is not only detected in acute myocarditis but is also detected during the chronic phase of the disease. Coxsackievirus B3 could evade immunological surveillance in a host dependent fashion, thus inducing a persistent infection of the myocardium in association with ongoing inflammation. Patterns of acute and persistent myocardial infection were quantitatively assessed in one representative mouse strain (A.CA/SnJ, H-2f) by applying computer-assisted digital image processing; these patterns were then related to the extent of myocardial tissue damage as well as to inflammation. We observed a strong correlation, both spatial and temporal, between viral replication and development of myocardial lesions, indicating that acute and chronic myocardial injuries are a consequence of multifocal organ infection. Analysis of strand-specific in situ hybridization revealed that viral replication in persistent infection is restricted at the level of RNA synthesis. The described procedure for quantitating organ infection provides a powerful tool for evaluating virus-host interactions and will be of particular interest to those studying human enterovirus-induced cardiomyopathies. PMID- 1309612 TI - Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells. AB - Hepatocyte growth factor (HGF) is a potent mitogen for primary hepatocytes. Therefore, we examined HGF as a possible autocrine growth factor in hepatocellular carcinoma (HCC). We introduced an albumin-HGF expression vector into Fao HCC cells and transgenic mice. Expression of the albumin-HGF vector in Fao HCC cells inhibited their growth in vitro. In vivo, FaoHGF cells produced tumors that averaged 10% of the sizes of G418-resistant controls when transplanted into nude mice. In contrast, hepatocytes from transgenic mice expressing HGF grew more rapidly than did those from normal siblings. Further, growth of eight additional HCC cell lines was inhibited by the addition of recombinant HGF. Finally, of 35 tumor cell lines surveyed, only 6 cell lines expressed HGF mRNA, and no HCC cell line expressed HGF. Although HGF stimulates normal hepatocytes, it is a negative growth regulator for HCC cells. PMID- 1309613 TI - Viral proteins associated with the Epstein-Barr virus transactivator, ZEBRA. AB - The BamHI Z Epstein-Barr replication activator (ZEBRA) mediates disruption of latency and induction of Epstein-Barr virus (EBV) early gene expression in latently infected lymphocytes. Polyclonal rabbit sera raised against ZEBRA were used to immunoprecipitate ZEBRA-associated proteins (ZAPs). ZAPs of 19, 21, 23, and 42 kDa were coimmunoprecipitated with ZEBRA from extracts of EBV-producing lymphoid cell lines. ZAPs were not recognized directly by the rabbit sera, but they were antigenic for EBV+ human sera. Immunoprecipitation of ZAPs by ZEBRA specific antisera required the presence of ZEBRA. ZAPs were not coprecipitated with ZEBRA from mouse cells expressing only ZEBRA, from Raji (a cell line in which EBV is unable to complete lytic replication), or from cells treated with inhibitors of viral DNA synthesis. Thus, ZAPs are late EBV-encoded proteins. ZEBRA and ZAPs colocalized to a salt-insoluble nuclear fraction, and both were found extracellularly in crude preparations of virions. ZAPs might function to affect the cellular localization of ZEBRA, to alter its capacity to transactivate, or to influence its target gene specificity. PMID- 1309614 TI - Isothermal in vitro amplification of DNA by a restriction enzyme/DNA polymerase system. AB - An isothermal in vitro DNA amplification method was developed based upon the following sequence of reaction events. Restriction enzyme cleavage and subsequent heat denaturation of a DNA sample generates two single-stranded target DNA fragments (T1 and T2). Present in excess are two DNA amplification primers (P1 and P2). The 3' end of P1 binds to the 3' end of T1, forming a duplex with 5' overhangs. Likewise, P2 binds to T2. The 5' overhangs of P1 and P2 contain a recognition sequence (5'-GTTGAC-3') for the restriction enzyme HincII. An exonuclease-deficient form of the large fragment of Escherichia coli DNA polymerase I (exo- Klenow polymerase) [Derbyshire, V., Freemont, P. S., Sanderson, M. R., Beese, L., Friedman, J. M., Joyce, C. M. & Steitz, T. A. (1988) Science 240, 199-201] extends the 3' ends of the duplexes using dGTP, dCTP, TTP, and deoxyadenosine 5'-[alpha-thio]triphosphate, which produces hemiphosphorothioate recognition sites on P1.T1 and P2.T2. HincII nicks the unprotected primer strands of the hemiphosphorothioate recognition sites, leaving intact the modified complementary strands. The exo- Klenow polymerase extends the 3' end at the nick on P1.T1 and displaces the downstream strand that is functionally equivalent to T2. Likewise, extension at the nick on P2.T2 results in displacement of a downstream strand functionally equivalent to T1. Nicking and polymerization/displacement steps cycle continuously on P1.T1 and P2.T2 because extension at a nick regenerates a nickable HincII recognition site. Target amplification is exponential because strands displaced from P1.T1 serve as targets for P2 and strands displaced from P2.T2 serve as targets for P1. A 10(6) fold amplification of a genomic sequence from Mycobacterium tuberculosis or Mycobacterium bovis was achieved in 4 h at 37 degrees C. PMID- 1309615 TI - Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration B mutant of Drosophila. AB - Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant. PMID- 1309616 TI - Components of the protein-excretion apparatus of Pseudomonas aeruginosa are processed by the type IV prepilin peptidase. AB - In the Gram-negative pathogen Pseudomonas aeruginosa, mutants in the gene for the prepilin peptidase (pilD) are pleiotropic, as they not only fail to process pilin but also accumulate in the periplasm, in their mature form, several toxins and hydrolytic enzymes that are normally exported to the external medium (excreted). We have suggested that this excretion defect is due to the lack of PilD-dependent processing of proteins that share sequences in common with the prepilin subunit and that are components of a protein-excretion machinery. In this paper we report the isolation and characterization of transposon-induced excretion mutants with phenotypes similar to that of a pilD gene mutant. Using oligonucleotide probes designed to recognize sequences encoding the cleavage site of the type IV prepilins, we have isolated four linked genes with the predicted putative PilD dependent cleavage site. Site-specific mutations within these genes have shown that they are required for protein excretion, and PilD-dependent processing of at least one of the four encoded proteins was demonstrated. Evidence suggests that similar components play a role in protein excretion in a wide variety of Gram negative bacteria. PMID- 1309617 TI - Immunoblots with rhodopsin antisera suggest that a purified mu opioid binding protein has structural characteristics of a G-protein-coupled receptor. AB - A mu opioid binding protein (OBP), previously purified to homogeneity from bovine striatal membranes, was examined by immunoblotting with six antisera against bovine rhodopsin. An antibody against the carboxyl-terminal tail of rhodopsin and one against membrane-associated rhodopsin gave strong signals at the appropriate molecular mass (65 kDa). An antibody directed against the first cytoplasmic loop of rhodopsin was weakly reactive. Three other antibodies did not recognize OBP. This pattern of crossreactivity was identical to that previously seen with beta adrenergic receptors. The existence of domains in the OBP, which are antigenically similar to those in two other guanine nucleotide regulatory protein coupled receptors, supports the hypothesis that mu opioid receptors have the structure characteristic of this receptor family. PMID- 1309619 TI - The spinal route--quo vadis? PMID- 1309618 TI - The cardiac conduction system in the rat expresses the alpha 2 and alpha 3 isoforms of the Na+,K(+)-ATPase. AB - The sodium pump is crucial for the function of the heart and of the cardiac conduction system, which initiates the heartbeat. The alpha (catalytic) subunit of this pump has three isoforms; the alpha 1 isoform is ubiquitous, but the alpha 2 and alpha 3 isoforms are localized to excitable tissue. Because rodent alpha 2 and alpha 3 isoforms are relatively sensitive to ouabain, which also slows cardiac conduction, we studied heart-cell-specific expression of pump isoform genes. Multiple conduction-system structures, including sinoatrial node, bundle branches, and Purkinje strands, had prominent, specific hybridization signal for alpha 2 and alpha 3 isoforms compared with adjacent working myocytes. This gene expression approach may be useful for labeling conduction tissue and also for localizing specific membrane channels and receptors in this system. PMID- 1309620 TI - Mammographic features predicting an extensive intraductal component in early stage infiltrating ductal carcinoma. AB - Several studies have shown that the presence of an extensive intraductal component in patients with infiltrating ductal carcinoma is a major factor for predicting local recurrence after breast-conserving surgery and radiotherapy. A prospective study of 101 consecutive mammograms in patients with stage I or II infiltrating ductal carcinoma was performed to determine the predictive values of mammographic features in determining the presence or absence of an extensive intraductal component. Thirty-five (35%) of the lesions contained a pathologically verified extensive intraductal component. Sixty-five percent (22/34) of lesions showing mammographic evidence of calcifications with or without a mass were associated with an extensive intraductal component (p less than .001). Lesions with calcifications greater than 3 cm in extent were significantly (p less than .05) more likely to have an extensive intraductal component (9/10; 90%) than those with calcifications less than 3 cm in extent (13/24; 54%). Only 17% (8/46) of patients in whom mammograms showed only a mass or architectural distortion and 24% (5/21) of patients who had a mass palpable clinically or who had normal findings on mammograms had lesions with an extensive intraductal component. We conclude that infiltrating ductal carcinomas associated with calcifications on mammography, especially if the calcifications are extensive, are likely to be associated with an extensive intraductal component. Carcinomas without calcifications that show masses or architectural distortion on mammography, or carcinomas with palpable masses and normal findings on mammography, are unlikely to have an extensive intraductal component. PMID- 1309622 TI - Bilateral femoral neuropathy caused by iliacus hematomas during anticoagulation after cardiac catheterization. PMID- 1309621 TI - Inotropic and lusitropic dysfunction in myocardium from patients with dilated cardiomyopathy. AB - Isometric force of contraction (DT), peak rate of tension increase (+T), peak rate of tension decrease (-T), time to peak tension (TPT), and time to half relaxation (T 1/2 T) were measured in electrically driven human papillary muscle strips (New York Heart Association [NYHA] class IV heart transplants, dilated cardiomyopathy; nonfailing (NF) donor hearts, brain dead) (1 Hz, 37 degrees C) under basal conditions (1.8 mmol/L Ca2+) and after stimulation with isoprenaline, ouabain, and Ca2+. There was no difference in the isometric contraction (+T, -T, TPT, and T 1/2 T) between NYHA IV hearts and NF hearts under basal conditions. Inotropic stimulation above 300% of basal DT increased -T significantly more in NF hearts (p less than 0.05) compared with NYHA IV hearts. The effectiveness of ouabain and Ca2+ to increase DT was not significantly changed in NYHA IV hearts compared with NF hearts. The isoprenaline-mediated increase in DT was reduced (p less than 0.05) in NYHA IV hearts to a similar extent (70%) as beta-adrenoceptors were downregulated. When the rate of stimulation was increased to 3 Hz (force frequency relationship), force of contraction increased only in NF preparations, whereas it decreased in NYHA IV myocardium (p less than 0.05). It was concluded that the contractile apparatus in terminally failing human myocardium is sufficient to maximally increase DT. During inotropic stimulation, abnormalities in diastolic rather than systolic contraction become evident. This may indicate abnormal intracellular Ca2+ handling. PMID- 1309623 TI - Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. AB - Cardiac dysfunction after cardiopulmonary bypass (CPB) has been reported by various investigators. Oxygen free radicals have been shown to depress cardiac function and contractility. To evaluate the possible role of oxygen free radicals (OFR) in post-pump cardiac dysfunction, measurements of cardiac function, OFR producing activity of polymorphonuclear (PMN) leukocytes (PMN chemiluminescence) and malondialdehyde (MDA), a lipid peroxidation product, in blood were made at induction of anesthesia (T1), before cross clamping of the aorta (T2), after closure of the chest (T3), and 24 hours postoperatively (T4) in 21 patients undergoing aortocoronary bypass surgery. The total OFR-derived chemiluminescence at T1, T2, T3, and T4 was 1590 +/- 156, 3169 +/- 338, 1972 +/- 214, and 2614 +/- 366 mv.min.10(6) PMN-1, respectively. Superoxide dismutase (SOD)-inhibitable chemiluminescence at T1, T2, T3, and T4 was 1214 +/- 129, 2674 +/- 328, 1752 +/- 215, and 2139 +/- 292 mv.min.10(6) PMN-1, respectively. Superoxide anion at T1, T2, T3, and T4 was 0.99 +/- 0.14, 1.30 +/- 0.17, 1.07 +/- 0.14, and 1.19 +/- 0.12 nmol.10(6) PMN-1.30 min-1, respectively. Blood MDA at T1, T2, T3, and T4 was 0.17 +/- 0.02, 0.25 +/- 0.03, 0.20 +/- 0.03, and 0.23 +/- 0.02 nmol/ml, respectively. OFR-derived and SOD inhibitable chemiluminescence, superoxide anion, and blood MDA increased significantly during CPB and postoperatively. There were decreases in the blood pressure and stroke volume, and increases in the central venous pressure, capillary wedge pressure, and heart rate during CPB and postoperatively. Cardiac output remained unchanged during this procedure. There was leukopenia during CPB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309625 TI - New antibiotics look good against M. avium. PMID- 1309624 TI - Mucolipidoses II and III variants with normal N-acetylglucosamine 1 phosphotransferase activity toward alpha-methylmannoside are due to nonallelic mutations. AB - Normal N-acetylglucosamine 1-phosphotransferase activity toward mono- and oligosaccharide acceptor substrates was detected in cultured skin fibroblasts from mucolipidoses II and III patients who were designated as variants (one of four mucolipidosis II and three out of six mucolipidosis III patients examined). The activity toward natural lysosomal protein acceptors was absent or deficient in cell preparations from all patients with classical as well as variant forms of mucolipidoses II and III. Complementation analysis, using fused and cocultivated mutant fibroblast combinations, revealed that, while cell lines with variant mucolipidosis III constituted a complementation group distinct from that of classical forms of mucolipidoses II and III, the variant mucolipidosis II cell line belonged to the same complementation group as did the classical forms. In contrast to the mutant enzyme from variant mucolipidosis III patients that failed to recognize lysosomal proteins as the specific acceptor substrates, the activity toward alpha-methylmannoside in the variant mucolipidosis II patient could be inhibited by exogenous lysosomal enzyme preparations (bovine beta-glucuronidase and human hexosaminidase A). These findings suggest that N-acetylglucosamine 1 phosphotransferase is composed of at least two distinct polypeptides: (1) a recognition subunit that is defective in the mucolipidosis III variants and (2) a catalytic subunit that is deficient or altered in the classical forms of mucolipidoses II and III as well as in the mucolipidosis II variant. PMID- 1309626 TI - Anesthesia for an unsuspected Lambert-Eaton myasthenic syndrome with autoantibodies and occult small cell lung carcinoma. PMID- 1309628 TI - Agency abandons HIV-related list. PMID- 1309627 TI - Long-lasting neuromuscular blockade from pipecuronium. PMID- 1309629 TI - [Etoposide and cisplatin combination chemotherapy in a patient with small cell lung carcinoma under artificial hemodialysis]. AB - A 70-year-old man with small cell carcinoma of the lung who was under artificial hemodialysis, was treated by combined administration of etoposide and cisplatin. Fifty mg. of etoposide in combination with 35 mg. of cisplatin were infused before dialysis. Before one hour and during dialysis, plasma etoposide and platinum levels decreased rapidly. No severe side effect was observed after the administration of etoposide and cisplatin. In conclusion, it was considered that cisplatin and etoposide could be given to the patient with malignant tumor under artificial hemodialysis. PMID- 1309630 TI - [A case of gastric cancer with multiple liver metastasis treated with transarterial and transportal chemoembolization of tegafur/lipiodol and epirubicin]. AB - A 56-year-old woman was admitted for advanced gastric cancer (S3H3N3P2 Stage IV). She underwent subtotal gastrectomy, left ovariectomy, and catheterization of the hepatic artery. Pre- and postoperative adjuvant chemotherapies consisting of tegafur, epirubicin, mitomycin C and cisplatin were performed. Two months after surgery, combination of transhepatic arterial and transportal chemoembolization with tegafur 400 mg/lipiodol 3 ml and epirubicin 20 mg was especially effective for this patient. The metastatic lesions of the liver regressed by 85% on computed tomography and the CEA level in the plasma decreased from 51.3 to 5.1 ng/ml. The response was judged partial response (PR), and the patient is now in good general condition. PMID- 1309631 TI - [Chemotherapy with high dose CBDCA for advanced non-small cell lung cancer]. PMID- 1309632 TI - [Evaluation of chemotherapy of unresectable non-small cell lung cancer]. AB - For this evaluation, a comparison was made of survival of 34 patients with non small cell lung cancer who had undergone chemotherapy (Group B) with that of 38 patients without this chemotherapy (Group A). Group B had received neither radiotherapy for primary lesions nor bronchial artery infusion of anticancer drugs, and the chemotherapeutic regimen was CDDP + VDS or CDDP + VDS + MMC chemotherapy. MST of this group was significantly longer than that of Group A (4.5 months vs 7.3 months. P less than 0.01), but the PS features of the two groups differed significantly. A comparison was thus made of survival for PS 1-2 cases in both groups (Group A: 17 cases, Group B: 27 cases). MST of group A and B were 6.8 and 9.8 months, respectively (P less than 0.05). The efficacy of the treatment for prolonging survival in terms of age, sex, PS, histology, T factor, N factor and M factor was evaluated by multivariate analysis using the proportional hazard model of Cox. The results obtained indicated the chemotherapy significantly prolonged survival. PMID- 1309633 TI - [Randomized trial of cisplatin plus ifosfamide versus cisplatin plus vindesine for non-small cell lung cancer (NSCLC)]. AB - Between 2/87 and 10/89, 83 patients (pts) with previously untreated NSCLC were assigned at random to receive either the PI regimen (cisplatin 80 mg/m2 dl and ifosfamide 2 g/m2 d 1, 2, 3, q 3-4 wks) or the PV regimen (cisplatin 80 mg/m2 d 1 and vindesine 3 mg/m2 d 1, 8, 15, q 3-4 wks). Three pts (2 PI regimen, 1 PV regimen) were ineligible for the study and 13 pts (7 PI regimen, 6 PV regimen) did not complete it. Thirty-three PI regimen pts and 34 PV regimen pts completed 2 or more cycles of the treatment and were evaluated. Patient characteristics were almost identical in both groups in terms of sex, age, pathological types, stage, performance status and number of chemotherapy cycles. For the PI regimen, there were 1 C.R. and 6 P.R., and the response rate was 21.2% (7/33). In the PV regimen, there were 11 P.R., and the response rate was 32.4% (11/34). The median survival time (MST) for PI regimen was 29 weeks (range 12-156 wks) and for PV regimen 40 weeks (range 8-138 wks). The difference in the survival curves for the 2 regimens was not statistically significant. Toxicities for the 2 regimens were similar except for greater leukopenia and one treatment-related death due to renal toxicity on PI regimen. These results suggest that PI regimen is not superior to PV regimen in the treatment of NSCLC. PMID- 1309634 TI - [Sequential MTX and 5-FU therapy of gastric cancer with systemic bone metastasis and disseminated intravascular coagulation]. AB - Sequential therapy consisting of methotrexate (MTX) and 5-FU was performed together with the administration of heparin and FOY in 10 cases of gastric cancer with disseminated intravascular coagulation (DIC) causing systemic bone metastasis. The ages of the subjects ranged from 29 to 65 years (median: 49 years) with systemic bone metastasis and bone marrow carcinosis observed in all cases. Histological types consisted of 6 cases of poorly differentiated adenocarcinoma, 2 cases of signet-ring cell carcinoma, and one case each of mucocellular and tubular adenocarcinoma. Therapy consisted of intravenous injection of 30 mg-100 mg/m2 (one case, 20 mg) of MTX followed three hours later by intravenous injection of 600 mg/m2 of 5-FU weekly. Determination of DIC was made in accordance with the DIC diagnostic standards of the Ministry of Health and Welfare, and determination of tumor effectiveness was based on gastric cancer handling codes. RESULTS: PR was observed in 3 cases. Diffuse metastasis observed in the entire lung field disappeared in one case, while remarkable improvement was observed in systemic bone metastasis in scintigram findings for the other 2 cases. All 3 cases were able to be discharged. Reduction of DIC score and absence of pain were observed in 8 cases. Based on the above, aggressive implementation of this treatment method is suggested. PMID- 1309635 TI - [Effect of dibutyryl cyclic AMP in the treatment of hepatocellular carcinoma- intraarterial infusion therapy combined with anticancer agent for hepatocellular carcinoma with portal vein thrombosis]. AB - Dibutyryl cyclic AMP was administered to 7 cases with hepatocellular carcinoma and its tumor thrombosis in portal vein, combined with intraarterial infusion of Mitomycin C or Adriamycin with implanted reservoir. Among these cases, tumor regressed in 5 cases, and therapeutic effect on tumor thrombosis was observed in 4 cases. The median survival time after initial treatment was about 5 months in 5 cases of Vp3, and more than 18 months in 2 cases of Vp2. Reduction of liver dysfunction by cholinesterase and hepaplastin test was found in most cases, and no severe side effects were observed. It is suggested that dibutyryl cyclic AMP has an antitumor effect on hepatocellular carcinoma, especially on its tumor thrombosis in portal vein, and also may assist in recovery from liver dysfunction. PMID- 1309636 TI - Cell fusion caused by herpes simplex virus-1 (HSV-1) strains tsB5 and MP is inhibited at pH 6.7 and pH 7.0. AB - We investigated the effect of different pH conditions on Vero cell cultures infected with herpes simplex virus-1 (HSV-1) wild-type strain KOS, and syncytial mutants HSV-1 HFEM (tsB5) and HSV-1 mp (MP). Cell fusion was inhibited when infected cells were continuously incubated with culture media adjusted to pH 6.7 or pH 7.0. Inhibition of cell fusion was rapidly reversible when infected cell cultures were returned to pH 7.5. The rate of synthesis and cell-surface expression of virus-specified glycoproteins gB, gC, gD, and gH were not affected during continuous incubation at pH 7.0, but they were reduced at pH 6.7 in comparison to pH 7.5. At later hours p.i. however, these glycoproteins continued to accumulate at all tested pH levels. Accumulation of infectious virions was substantially reduced for MP, KOS, and tsB5 at pH 6.7. At pH 7.0, KOS and tsB5 titers were greatly reduced but MP titers were not affected. PMID- 1309637 TI - Immunoperoxidase tracing of Junin virus neural route after footpad inoculation. AB - To determine the pathway adopted by peripherally inoculated Junin virus (JV) to reach the CNS, rat tissues were serially harvested to trace the sequence of viral progression from right hind footpad to brain. Immunoperoxidase (PAP) labeling of viral antigen, concomitantly with infectivity assays and histological examination of each selected sample, were carried out. As from the 2nd week post-infection (pi), neurological disease inducing 100% mortality at 1 month was evident. At day 5 pi, viral antigen was first detected at footpad level in epidermic and dermic cells, as well as in neighbouring myocytes; labeled macrophages infiltrating small nerve branches were also disclosed. As from 10-15 days pi, viral antigen became apparent along ipsilateral sciatic nerve structures and within lumbar spinal ganglion neurons, followed by a fast viral spread throughout CNS neurons that involved spinal cord and brain. Concurrent histopathology featured minimal inflammatory reaction together with generalized astrocytic activation. Hematogenous viral transport was negligible, since JV was isolated much earlier and in higher infectivity titers in neural tissues than in blood. It may be concluded that after viral replication in footpad, JV neural route was demonstrated by its PAP labeling from peripheral nerves to cerebral cortex. PMID- 1309638 TI - Maternally-derived passive immunity to enterotropic mouse hepatitis virus. AB - Maternally-derived antibody to enterotropic mouse hepatitis virus (MHV) strain Y was transferred to pups by both intrauterine (IgG) and lactogenic (IgA and IgG) routes. Antibody present in the gastric whey of pups suckling immune dams dropped to undetectable levels by weaning age (21 days post partum). MHV-specific IgG was found in the serum of passively immune pups up to 10 weeks of age. Immune dams transferred equal levels of antibody to 3 consecutive litters of pups, without evidence of decline. Immunoblots showed that IgA and IgG in whey and serum were directed against nucleoprotein N and glycoprotein S. MHV-specific IgM was not detected in any sample. PMID- 1309640 TI - Adaptation of transmissible gastroenteritis virus to growth in non-permissive Vero cells. AB - The CPK cells derived from swine kidney were infected with the attenuated TO-163 strain of transmissible gastroenteritis (TGE) virus, and fused with uninfected Vero cells in the presence of polyethylene glycol. Repeated cocultivation of the fused cells with uninfected Vero cells rendered the virus to grow in Vero cells. The Vero cell-adapted virus acquired the ability to infect and produce cytopathic effects in several other non-permissive cell lines of non-porcine origin. No major differences in viral polypeptides were shown between the Vero cell-adapted TO-163 strain and its parent strain by indirect immunofluorescence and Western blotting using monoclonal and polyclonal antibodies to TGE virus. PMID- 1309639 TI - Anti-idiotypic antibodies to bovine herpesvirus-1 inhibit virus infection in cell cultures. AB - A panel of murine monoclonal antibodies (MAbs) to bovine herpesvirus-1 (BHV-1) was prepared. Three of them were neutralizing MAbs and reacted against 130/75/50 kDa, 77 kDa, or 97 kDa glycoproteins (gp). A fourth non-neutralizing MAb recognized the 97 kDa gp. Competition radioimmunoassay demonstrated that each of the four MAbs reacted against a different virus epitope. Anti-idiotypic antibodies (anti-id) to the four MAbs were produced in rabbits and purified by sequential immunoaffinity chromatography. Each anti-id inhibited the binding of its respective MAb to BHV-1 in competitive ELISA and blocked BHV-1 neutralizing activity of the MAb. This inhibition suggested that the anti-ids were specific for the antigen binding site of the MAbs. Treatment of MDBK cells with anti-ids inhibited BHV-1 infection, which suggested that the anti-ids block a cellular component essential for virus infection. Absence of significant cross-reactivity among the anti-ids for heterologous MAbs indicated that they recognized unique determinants on the antigen binding site of the homologous MAb. PMID- 1309641 TI - Latency and reactivation of a thymidine kinase-negative bovine herpesvirus 1 deletion mutant. AB - A bovine herpesvirus 1 (BHV 1) mutant variant with a deletion in the thymidine kinase (TK) gene was assessed for its ability to establish latency and be reactivated in cattle. After treatment with dexamethasone, reactivated TK- BHV 1 was isolated from one of four cattle that received virus by intravenous inoculation only, and from four of four cattle that received virus by intranasal, intravaginal, and intravenous inoculation. Results prove that TK- BHV 1 will establish latency and can be reactivated in the natural host. PMID- 1309642 TI - Follicular dendritic cell-B cell interactions in virus disease. Common localization but different cell damage caused by antibody immobilized virus? AB - Follicular dendritic cells (FDC) are involved in the trapping and retention of antigen-antibody complexes in lymphoid follicles. This FDC immobilized antigen is thought to be involved in the generation of memory B-lymphocytes. Follicular trapping of both Aleutian disease virus and HIV particles has been demonstrated. However as far as known their affects on FDC and follicular B-cells are completely different. It is hypothesized that the trapping of (antibody complexed) virus particles by the FDC-network may have an important role in several virus diseases. PMID- 1309643 TI - Hybridization relatedness of Israeli and U.S. bluetongue (BLU) serotypes using cDNA probes from BLU virus strain 11-UC8. AB - Partial cDNA clones representing 47%, 96%, and 98% of genome segments 7, 9, and 10, respectively, of a US bluetongue virus (BLU) 11 virulent strain were used to study, for the first time, the genetic relationships between Israeli BLU proto serotypes and field isolates, and US BLU proto-serotypes. Their usefulness as group-specific identification probes was also determined. The viral nucleic acid was extracted from the infected cells and the purified dsRNA genome segments were fractionated by polyacrylamide gel electrophoresis, transferred to a nylon membrane and hybridized to the 32P labeled DNA probes. The three probes recognized all the samples tested. Genome segment 7, that code for the mayor inner capsid protein VP7, showed the most variation in the hybridization signal with the US proto-serotypes and all the Israeli samples studied. The genome segments 9 and 10 that code for the minor inner capsid protein VP6 and the nonstructural protein NS3, respectively, were highly conserved in all the samples tested despite their distant geographical regions of origin. The last two mentioned clones showed to be good group-specific probes for the identification of BLU samples from Israel and United States. The obtained cloned genetic probes were also tested against US epizootic haemorrhagic disease virus (EHDV) serotype 1 and 2 viral dsRNA, a distantly related orbivirus. None of them hybridized with the viral dsRNA of these two viruses. PMID- 1309644 TI - Viremic dissemination of mouse hepatitis virus-JHM following intranasal inoculation of mice. AB - Using a sensitive infant mouse bioassay to detect infectious virus, the pattern of mouse hepatitis virus (MHV) JHM dissemination in blood and other tissues was examined during the first 5 days following intranasal inoculation. MHV replicated in nasal turbinates of both susceptible BALB and resistant SJL mice from days 1 through 5, but BALB mice had higher titers on days 1 and 2. Viremia was detectable on days 1 through 5 in BALB mice, but only on days 3 and 5 in SJL mice. Transient virus replication occurred in the lungs of both mouse genotypes at 1 and 2 days, then ceased. This correlated with more consistently demonstrable virus in blood collected from the left atrium of the heart, compared to jugular vein, portal vein and right atrial blood. Virus was associated equally with the plasma and cellular fractions of blood on day 3, but was primarily in the buffy coat of the cellular fraction on day 5. Interferon-alpha/beta was detected in serum and spleen, but not liver or brain of BALB mice or in any tissue of SJL mice. BALB serum and spleen interferon was first detected at 36 h, peaked between 48 and 72 h, and was undetectable by 108 h. The distribution of virus in nose, cervical, axillary and mesenteric lymph nodes, spleen, Peyer's patch, thymus, bone marrow and liver was examined at 1, 2, and 3 days. The resulting pattern suggested lymphatic spread of virus to cervical lymph node and mesenteric lymph node as pathways of dissemination in addition to viremia. PMID- 1309645 TI - Inhibition of herpes simplex virus production in vitro by cyclosporin A. AB - Nontoxic concentrations of Cyclosporin A (CyA) dose-dependently inhibited herpes simplex virus (HSV) production in resting monkey kidney cells. The block was at the step of virus DNA synthesis as assessed by [3H]thymidine incorporation and by dot blot hybridization of infected cell DNA using a cloned 32P-labelled HSV DNA fragment (BamHI X) as probe. This was further supported by analysis of HSV protein synthesis in the presence of CyA as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot. A relative accumulation of HSV alpha- (e.g., ICP 4) and beta 1-proteins (e.g., ICP 6 and 8) was found, whereas HSV gamma 1-proteins were slightly decreased and gamma 2-proteins were markedly decreased by CyA. The production of thymidine kinase and DNA polymerase was decreased when CyA was added to HSV infected cells. The sensitivity to CyA was not escaped by thymidine kinase nor DNA polymerase deficient mutants. Passage of HSV in presence of CyA did not result in induction of drug resistance. PMID- 1309646 TI - The influence of arrestin (48K protein) and rhodopsin kinase on visual transduction. AB - The shutoff of the phototransduction cascade in retinal rods requires the inactivation of light-activated rhodopsin. The underlying mechanisms were studied in functionally intact detached rod outer segments by testing the effect of either sangivamycin, an inhibitor of rhodopsin kinase, or phytic acid, an inhibitor of 48K protein binding to phosphorylated rhodopsin, on light responses recorded in whole-cell voltage clamp. The results suggest that isomerized rhodopsin is inactivated fully by multiple phosphorylation and that the binding of 48K protein accelerates recovery by quenching partially phosphorylated rhodopsin. Higher concentrations of sangivamycin cause changes in the light response that cannot be explained by selective inhibition of rhodopsin kinase and suggest that other protein kinases are needed for normal rod function. PMID- 1309647 TI - Calcium influx through nicotinic receptor in rat central neurons: its relevance to cellular regulation. AB - The Ca2+ permeability of a nicotinic acetylcholine receptor (nAChR) in the rat CNS was determined using both current and fluorescence measurements on medial habenula neurons. The elementary slope conductance of the nAChR channel was 11 pS in pure external Ca2+ (100 mM) and 42 pS in standard solution. Ca2+ influx through nAChRs resulted in the rise of cytosolic Ca2+ concentration ([Ca2+]i) to the micromolar range. This increase was maximal under voltage conditions (below 50 mV) in which Ca2+ influx through voltage-activated channels was minimal. Ca2+ influx through nAChRs directly activated a Ca(2+)-dependent Cl- conductance. In addition, it caused a decrease in the GABAA response that outlasted the rise in [Ca2+]i. These results underscore the physiological significance of Ca2+ influx through nAChR channel in the CNS. PMID- 1309648 TI - Ciliary neurotrophic factor prevents neuronal degeneration and promotes low affinity NGF receptor expression in the adult rat CNS. AB - Recombinant human ciliary neurotrophic factor (CNTF) was infused for 2 weeks into the lateral ventricle of fimbria-fornix transected adult rats, and its effects were compared with those of purified mouse nerve growth factor (NGF). We provide evidence that CNTF can prevent degeneration and atrophy of almost all injured medial septum neurons (whereas NGF protects only the cholinergic ones). CNTF is also involved in up-regulation of immunostainable low affinity NGF receptor (LNGFR) in cholinergic medial septum and neostriatal neurons and in a population of lateral septum neurons. In contrast to NGF, CNTF did not stimulate choline acetyltransferase in the lesioned septum and normal neostriatum (pointing to different mechanisms for the regulation of choline acetyltransferase and LNGFR), cause hypertrophy of septal or neostriatal cholinergic neurons, or cause sprouting of LNGFR-positive (cholinergic) septal fibers. PMID- 1309649 TI - A family of metabotropic glutamate receptors. AB - Three cDNA clones, mGluR2, mGluR3, and mGluR4, were isolated from a rat brain cDNA library by cross-hybridization with the cDNA for a metabotropic glutamate receptor (mGluR1). The cloned receptors show considerable sequence similarity with mGluR1 and possess a large extracellular domain preceding the seven putative membrane-spanning segments. mGluR2 is expressed in some particular neuronal cells different from those expressing mGluR1 and mediates an efficient inhibition of forskolin-stimulated cAMP formation in cDNA-transfected cells. The mGluRs thus form a novel family of G protein-coupled receptors that differ in their signal transduction and expression patterns. PMID- 1309650 TI - Efficient expression of rat brain type IIA Na+ channel alpha subunits in a somatic cell line. AB - Type IIA rat brain Na+ channel alpha subunits were expressed in CHO cells by nuclear microinjection or by transfection using a vector containing both metallothionein and bacteriophage SP6 promoters. Stable cell lines expressing Na+ channels were isolated, and whole-cell Na+ currents of 0.9-14 nA were recorded. The mean level of whole-cell Na+ current (4.5 nA) corresponds to a cell surface density of approximately 2 channels active at the peak of the Na+ current per microns 2, a density comparable to that observed in the cell bodies of central neurons. The expressed Na+ channels had the voltage dependence, rapid activation and inactivation, and rapid recovery from inactivation characteristic of Na+ channels in brain neurons, bound toxins at neurotoxin receptor sites 1 and 3 with normal properties, and were posttranslationally processed to a normal mature size of 260 kd. Expression of Na+ channel cDNA in CHO cells driven by the metallothionein promoter accurately and efficiently reproduces native Na+ channel properties and provides a method for combined biochemical and physiological analysis of Na+ channel structure and function. PMID- 1309651 TI - Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. AB - The primary structures of human neuronal alpha 1, alpha 2, and beta subunits of a voltage-dependent Ca2+ channel were deduced by characterizing cDNAs. The alpha 1 subunit (alpha 1D) directs the recombinant expression of a dihydropyridine sensitive L-type Ca2+ channel when coexpressed with the beta (beta 2) and the alpha 2 (alpha 2b) subunits in Xenopus oocytes. The recombinant channel is also reversibly blocked by 10-15 microM omega-conotoxin. Expression of the alpha 1D subunit alone, or coexpression with the alpha 2b subunit, did not elicit functional Ca2+ channel activity. Thus, the beta 2 subunit appears to serve an obligatory function, whereas the alpha 2b subunit appears to play an accessory role that potentiates expression of the channel. The primary transcripts encoding the alpha 1D, alpha 2, and beta subunits are differentially processed. At least two forms of neuronal alpha 1D were identified. Different forms of alpha 2 and beta transcripts were also identified in CNS, skeletal muscle, and aorta tissues. PMID- 1309652 TI - Omega-conotoxin GVIA blocks a Ca2+ current in bovine chromaffin cells that is not of the "classic" N type. AB - Previous studies have identified two components of whole-cell Ca2+ current in bovine chromaffin cells. The "standard" component was activated by single depolarizations, while "facilitation" could be activated by large prepulses or repetitive depolarizations. Neither current component was sensitive to changes in holding potential between -100 and -50 mV; thus neither appeared to be carried by N-type Ca2+ channels. We now report that the facilitation Ca2+ current is insensitive to omega-conotoxin GVIA (omega-CgTx), but that the toxin blocks approximately 50% of the standard Ca2+ current. In some cells the toxin blocks all of the standard Ca2+ current, in others about half of the current, while in others it has no effect. Kinetic differences in current activation are observed after toxin application. These results suggest that the standard component of chromaffin cell Ca2+ current is composed of two pharmacologically distinct channels-one is omega-CgTx sensitive and the other is not. Two kinetically distinct types of 14 pS Ca2+ channels that may correspond to the omega-CgTx sensitive and -insensitive components were observed in single-channel experiments. Because omega-CgTx blocked Ca2+ channels that were not inactivated by a depolarized holding potential, the commonly used Ca2+ channel categorization scheme may be inadequate to describe the Ca2+ channels found in chromaffin cells. PMID- 1309653 TI - The effect of lysophosphatidylcholine on the activity of various mitochondrial enzymes. AB - The influence of lysophosphatidylcholine (LPC) on H(+)-ATPase, cytochrome oxidase (COX), glycerolphosphate dehydrogenase (GPDH) and malate dehydrogenase (MDH) was followed. The activities of H(+)-ATPase and COX increased with increasing LPC concentration up to 0.5 mg/mg protein when maxima were achieved. This activatory effect is LPC-specific, because Lubrol-treated or frozen-thawed mitochondria showed lower activities of these enzymes. H(+)-ATPase was not influenced by higher concentration of LPC, while COX activity decreased with increasing amount of LPC. The activity of GPDH decreased at very low concentration of LPC and was not further modified at higher LPC concentration. In an attempt to find the concentration of LPC necessary for a complete permeabilization of inner mitochondrial membrane we followed the influence of lysolipid on the release of MDH activity from the mitochondrial matrix. The full activity of this enzyme was obtained with a concentration 0.75 mg LPC/mg protein indicating that mitochondria were completely broken. Our data indicate that LPC significantly affects activity of enzymes connected with mitochondrial membrane and can be useful for evaluation of the importance of phospholipid microenvironment for the enzyme function. PMID- 1309654 TI - Characterization of a mitochondrial inorganic pyrophosphatase in Saccharomyces cerevisiae. AB - We have studied a mitochondrial inorganic pyrophosphatase (PPase) in the yeast Saccharomyces cerevisiae. The uncoupler FCCP (carbonyl cyanide p trifluoromethoxyphenylhydrazone) and the ionophores valinomycin and nigericin stimulate the PPase activity of repeatedly washed yeast mitochondria 2-3-fold. We have previously cloned a yeast gene, PPA2, encoding the catalytic subunit of a mitochondrial PPase. Uncouplers stimulate the PPase activity several-fold in mitochondria from both cells that overexpress PPA2 from a high copy number plasmid and cells with normal expression. These results indicate that the PPA2 polypeptide functions as an energy linked and membrane associated PPase. The stimulation of mitochondrial PPase activity by FCCP, but not by valinomycin and nigericin, was greatly enhanced by the presence of DTT. The antibiotics Dio-9, equisetin and the F0F1-ATPase inhibitor oligomycin also increase mitochondrial PPase activity several fold. This stimulation is much higher, whereas basal PPase activity is lower, in isotonic than in hypotonic solution, which indicates that intact membranes are a prerequisite for maximal effects. PMID- 1309655 TI - The contribution of adenine nucleotide loss to ischemia-induced impairment of rat kidney cortex mitochondria. AB - Adenine nucleotides and respiration were assayed with rat kidney mitochondria depleted of adenine nucleotides by pyrophosphate treatment and by normothermic ischemia, respectively, with the aim of identifying net uptake of ATP as well as elucidating the contribution of adenine nucleotide loss to the ischemic impairment of oxidative phosphorylation. Treatment of rat kidney mitochondria with pyrophosphate caused a loss of adenine nucleotides as well as a decrease of state 3 respiration. After incubation of pyrophosphate-treated mitochondria with ATP, Mg2+ and phosphate, the content of adenine nucleotides increased. We propose that kidney mitochondria possess a mechanism for net uptake of ATP. Restoration of a normal content of matrix adenine nucleotides was related to full recovery of the rate of state 3 respiration. A hyperbolic relationship between the matrix content of adenine nucleotides and the rate of state 3 respiration was observed. Mitochondria isolated from kidneys exposed to normothermic ischemia were characterized by a decrease in the content of adenine nucleotides as well as in state 3 respiration. Incubation of ischemic mitochondria with ATP, Mg2+ and phosphate restored the content of adenine nucleotides to values measured in freshly-isolated mitochondria. State 3 respiration of ischemic mitochondria reloaded with ATP recovered only partially. The rate of state 3 respiration increased by ATP-reloading approached that of uncoupler-stimulated respiration measured with ischemic mitochondria. These findings suggest that the decrease of matrix adenine nucleotides contributes to the impairment of ischemic mitochondria as well as underlining the occurrence of additional molecular changes of respiratory chain limiting the oxidative phosphorylation. PMID- 1309656 TI - Blockade of sodium channels by Bistramide A in voltage-clamped frog skeletal muscle fibres. AB - The effect of Bistramide A, a toxin isolated from Bistratum lissoclinum Sluiter (Urochordata), on the peak sodium current (INa) of frog skeletal muscle fibres was studied with the double sucrose gap voltage clamp technique. External or internal application of Bistramide A inhibited INa without alteration of the kinetic parameters of the current nor of the apparent reversal potential for Na. The steady-state activation curve of INa was unchanged while the steady-state inactivation curve of INa was shifted towards more negative membrane potentials. Dose-response curves indicated an apparent dissociation constant for Bistramide A of 3.3 microM and a Hill coefficient of 1.2 which suggested a one to one relation between the toxin and Na channel. The inhibition of INa occurred at rest, and was more important at more positive holding potentials. Bistramide A exhibited only a weak frequency-dependent effect. The toxin did not interact with the use dependent effect of lidocaine. It mainly blocked Na channels at more depolarized holding potentials. The toxin blocked Na channels when it was internally applyed and when the inactivation gating system has been previously destroyed by internal diffusion of iodate. The data suggest that Bistramide A inhibited the Na channel both at rest and in the inactivated state and occupied a site which was not located on the inactivation gate. PMID- 1309657 TI - Platelet membrane phosphatidylinositol kinase activity. Triton X-100 effects provide evidence for intramicellar reaction. AB - Phosphatidylinositol (PI) kinase activity of platelet membranes was solubilized and partially purified by anion-exchange chromatography to measure the initial enzymatic rates. Kinetic studies were performed in the presence of Triton X-100 to obtain mixed micelles. The partially purified enzyme exhibited a Michaelian behaviour towards ATP, with a Km of 58 microM. The enzymatic rates were dependent upon Triton concentrations. Upon increasing its concentration, this detergent exhibited an activating effect followed by an inhibitory one. The optimal micellar Triton concentration was proportionnal to the PI concentration used in the assay. Conversely, the behaviour of the enzyme towards PI was dependent upon the Triton concentration. However, when PI concentration was expressed as its surfacic concentration within the micelles, the activity became independent of the detergent concentration, and a Km value of 0.09 mol/mol was estimated. Therefore, in vitro phosphorylation of phosphatidylinositol by PI kinase is rate limited by an intramicellar reaction, and provides a study model for the in vivo reaction. PMID- 1309658 TI - Proteinases inhibit H(+)-ATPase and Na+/H+ exchange but not water transport in apical and endosomal membranes from rat proximal tubule. AB - A marked increase in water permeability can be induced in Xenopus oocytes by injection of mRNA from tissues that express water channels, suggesting that the water channel is a protein. In view of this and previous reports which showed that proteinases may interfere with mercurial inhibition of water transport in red blood cells (RBC), we examined the influence of trypsin, chymotrypsin, papain, pronase, subtilisin and thermolysin on water permeability as well as on ATPase activity, H(+)-pump, passive H+ conductance, and Na+/H+ exchange in apical brush-border vesicles (BBMV) and endosomal (EV) vesicles from rat renal cortex. H+ transport was measured by Acridine orange fluorescence quenching and water transport by stopped-flow light scattering. As measured by potential-driven H+ accumulation in BBMV and EV, proteinase treatment had little effect on vesicle integrity. In BBMV, ecto-ATPase activity was inhibited by 15-30%, Na+/H+ exchange by 20-55%, and H+ conductance was unchanged. Osmotic water permeability (Pf) was 570 microns/s and was inhibited 85-90% by 0.6 mM HgCl2; proteinase treatment did not affect Pf or the HgCl2 inhibition. In EV, NEM-sensitive H+ accumulation and ATPase activity were inhibited by greater than 95%. Pf (140 microns/s) and HgCl2 inhibition (75-85%) were not influenced by proteinase treatment. SDS-PAGE showed selective digestion of multiple polypeptides by proteinases. These results confirm the presence of water channels in BBMV and EV and demonstrate selective inhibition of ATPase function and Na+/H+ exchange by proteinase digestion. The lack of effect of proteinases on water transport by mercurials. We conclude that the water channel may be a small integral membrane protein which, unlike the H(+) ATPase and Na+/H+ exchanger, has no functionally important membrane domains that are sensitive to proteolysis. PMID- 1309659 TI - Parathyroid hormone stimulates ATP-dependent calcium pump activity by a different mode in proximal and distal tubules of the rat. AB - A new technique was developed to isolate basolateral membrane vesicles individually from proximal and distal tubules of the rat cortex. This new technique enabled us to study differences in their kinetics and mechanisms of hormonal regulation of Ca pump between proximal and distal tubules. The Ca pump in distal tubule has very high affinity (42.6 nM Ca2+) and the one in proximal tubule has relatively low affinity (75.6 nM Ca2+). Parathyroidectomy (PTX) decreased the Vmax of Ca pump activity in proximal tubule (4.68 +/- 0.99 vs. 9.08 +/- 2.21 nmol 45Ca2+/min per mg protein BLMV, P less than 0.05), while it increased Km in distal tubule (93.1 +/- 11.0 vs. 35.1 +/- 16.1 nM Ca2+, P less than 0.05). Restoration of serum Ca2+ concentration by 1,25(OH)2D3 supplement could not reverse these changes by PTX in Ca pump activity in either the proximal or the distal tubule. In conclusion, this study strongly suggested that parathyroid hormone stimulated Ca pump activity by increasing the Vmax in proximal tubule and by increasing the affinity in distal tubule. 1,25(OH)2D3 does not have a direct effect on the basolateral membrane Ca pump activity. PMID- 1309660 TI - Amphipathic interactions of cannabinoids with membranes. A comparison between delta 8-THC and its O-methyl analog using differential scanning calorimetry, X ray diffraction and solid state 2H-NMR. AB - The effects of (-)-delta 8-tetrahydrocannabinol (delta 8-THC) and its biologically inactive O-methyl ether analog on model phospholipid membranes were studied using a combination of differential scanning calorimetry (DSC), small angle X-ray diffraction and solid state 2H-NMR. The focus of this work is on the amphipathic interactions of cannabinoids with membranes and the role of the free phenolic hydroxyl group which is the only structural difference between these two cannabinoids. Identically prepared aqueous multilamellar dispersions of phosphatidylcholines in the absence and presence of cannabinoids were used. The DSC thermograms and X-ray diffraction patterns of these preparations allowed us to detect the strikingly different manners in which these two cannabinoids affect the thermotropic properties and the thickness of the bilayer. In order study the effects of the cannabinoids on different regions of the bilayer, we used solid state 2H-NMR with four sets of model membranes from dipalmitoylphosphatidylcholine deuterated in different sites, viz., the choline trimethylammonium head group, or one of the following three groups in the acyl chains; the 2'-methylene, 7'-methylene, 16'-methyl groups. Analysis of quadrupolar splittings indicated that delta 8-THC resides near the bilayer interface and the inactive analog sinks deeper towards the hydrophobic region. The temperature dependence of the solid state 2H-NMR spectra showed that, during the bilayer phase transition, the disordering of the choline head groups is a separate event from the melting of the acyl chains, and that amphipathic interactions between delta 8-THC and the membrane separate these two events further apart in temperature. The inactive analog lacks the ability to induce such a perturbation. PMID- 1309661 TI - Interfacial ionization and partitioning of membrane-bound local anesthetics. AB - Consideration of the interfacial protonation equilibria of membrane-associated amphiphiles indicates that the partition coefficients of the protonated and unprotonated species will differ considerably. The partition coefficients of the charged and uncharged forms of spin-labelled myristic acid in dimyristoylphosphatidylcholine bilayer dispersions have been measured by EPR spectroscopy and found to be approximately 140-fold higher for the protonated acid than for the dissociated salt form. This ratio of partition coefficients is found to be in good agreement with that predicted from the interfacial shift in pKa of the fatty acid on its partitioning into the membrane. The latter was determined from the changes in the EPR spectra of the membrane-associated fatty acid with pH and was found to be +2.1 pH units. The interfacial shifts in pKa for a series of spin-labelled analogues of tertiary amine local anaesthetics have been determined from the pH dependence of the partition coefficients in dimyristoylphosphatidylcholine bilayer dispersions and are found mostly to be in the range of approx. -1.0 to -1.5 pH units, corresponding to a 10- to 30-fold higher partition coefficient of the uncharged base compared with that of the charged ammonium form. PMID- 1309662 TI - Phosphatase activity and potassium transport in liposomes with Na+,K(+)-ATPase incorporated. AB - We have used liposomes with incorporated pig kidney Na+,K(+)-ATPase to study vanadate sensitive K(+)-K+ exchange and net K+ uptake under conditions of acetyl- and p-nitrophenyl phosphatase activities. The experiments were performed at 20 degrees C. Cytoplasmic phosphate contamination was minimized with a phosphate trapping system based on glycogen, phosphorylase a and glucose-6-phosphate dehydrogenase. In the absence of Mg2+ (no phosphatase activity) 5-10 mM p nitrophenyl phosphate slightly stimulated K(+)-K+ exchange whereas 5-10 mM acetyl phosphate did not. In the presence of 3 mM MgCl2 (high rate of phosphatase activity) acetyl phosphate did not affect K(+)-K+ exchange whereas p-nitrophenyl phosphate induced a greater stimulation than in the absence of Mg2+; a further addition of 1 mM ADP resulted in a 35-65% inhibition of phosphatase activity with an increase in K(+)-K+ exchange, which sometimes reached the levels seen with 5 mM phosphate and 1 mM ADP. The net K+ uptake in the presence of 3 mM MgCl2 was not affected by acetyl phosphate or p-nitrophenyl phosphate, whereas it was inhibited by 5 mM phosphate (with and without 1 mM ADP). The results of this work suggest that the phosphatase reaction is not by itself associated to K+ translocation. The ADP-dependent stimulation of K(+)-K+ exchange in the presence of phosphatase activity could be explained by the overlapping of one or more step/s of the reversible phosphorylation from phosphate with the phosphatase cycle. PMID- 1309663 TI - The role of surface charge and hydrophilic groups on liposome clearance in vivo. AB - The effect of negative surface charge and hydrophilic groups on liposome clearance from blood was investigated in mice using liposome-entrapped 67gallium deferoxamine as a label. The presence of negatively-charged lipids may retard or accelerate liposome clearance. Physicochemical features contributing to optimal retardation of liposome clearance include a hydrophilic carbohydrate moiety and a sterically hindered negatively-charged group. The relevance of the negative charge steric effect is suggested by the finding that phosphatidylinositol phosphate (PIP) and trisialoganglioside (GT1) are less effective than phosphatidylinositol (PI) and monosialoganglioside (GM1), respectively, in retarding liposome clearance. The need for negative charge in addition to the carbohydrate group for optimal effect on retardation of clearance is indicated by the observation that asialoganglioside (AGM1) is less effective than GM1 in this respect. The negative charge effect is observed with liposome bilayers having both low and high temperature phase-transitions. Increasing the molar fraction of negatively-charged lipid (hydrogenated PI derived from soya) from 23 to 41% resulted in a dramatic acceleration of liposome clearance. The clearance accelerating effect of the high negative charge was specifically directed to the liver with selective reduction of spleen uptake. Increasing liposome size also had an accelerating effect on clearance but in this case it was accompanied by a non-specific concomitant increase of both liver and spleen uptake. PMID- 1309664 TI - Partite expression of the bovine papillomavirus E1 open reading frame in Escherichia coli. AB - Six recombinants were constructed which expressed portions of the bovine papillomavirus E1 open reading frame as OmpF/E1/beta-galactosidase tribrid fusion proteins in Escherichia coli. Rabbit sera containing E1-specific antibodies were generated against five of these six fusion proteins (which together constitute 74% of the full-length E1 open reading frame). The individual fusion proteins and their cognate antisera will be useful reagents for defining the structure and function of the BPV E1 protein(s). PMID- 1309665 TI - Cloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins. AB - Several cDNA clones encoding a collagen-binding protein were isolated from human fibroblasts. The cDNA encoded a 417 amino acid protein, containing two potential N-linked oligosaccharide binding sites and a C-terminal RDEL sequence, which has been shown to act as an endoplasmic retention signal in other systems. The derived amino acid sequence of the protein shows close homology with gp46 from rat skeletal myoblasts, J6 protein from mouse F9 embryonal carcinoma cells and hsp47 from chick embryo fibroblasts. It also shows sequence similarity with members of the serpin family. PMID- 1309666 TI - Formation and ultrastructure of somatic cell hybrids. AB - Taken altogether, the EM evidence we have obtained indicates that the induced (both viral and PEG) and spontaneous (entrance of a splenocyte into a cell) fusion of mammalian somatic cells are associated with alterations in the structure of fusing cells. For example there are alterations in the structure of not only the surfaces of fusing cells but also in the nucleus envelopes and cytoplasmic organelles after PEG treatment. Also, there is long retention of cellular plasma membrane remnants in virally-induced heterokaryons. In short, for each case the alterations were unquestionably specific, in response to the imposed challenge. These specific features not only determine the efficiency and rate of fusion, but also the mode of which the hybrid nucleus is formed. This mode directly determines the fate of the synkaryon and the stability of the so formed hybrid genome. It might be thought that an increase in the inner nuclear envelope observed in some hybrids would counteract the consequences of the disproportion arising between the increase in cell volume and nuclear surface. The finger-like invaginations of the hybrid nuclei nuclear envelope, surrounded by replicatively and transcriptionally active chromatin, appear to be EM demonstrations of such counteracting mechanisms. These invaginations, by augmenting the available inner layer, most likely increase the anchorage sites for chromatin. It is noteworthy that the invaginations occur mainly in multichromosomal hybrids with little chromosome loss. It appears possible that some of the hybrids may contain particular chromosomes from the more differentiated parent cell. PMID- 1309667 TI - Image analysis of gap junction structures. AB - Isolated gap junction plaques contain hexagonal crystalline arrays of membrane channels called connexons which are a suitable specimen for electron crystallography. Image analysis of gap junction lattices has shown that while there is sufficient lattice order for structural analysis to approximately 25 A, there is enough disorder in both the lattice and the connexon to create a family of related images. This review is focused on how these images can be interpreted in terms of what is known about both the connexon and its constituent protein, connexin. PMID- 1309668 TI - Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid "resistance" in patients with acute promyelocytic leukemia. AB - Although all-trans retinoic acid (RA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), all groups have described clinical relapses despite continued RA treatment. This finding suggests that resistance to the cytodifferentiating effects of the retinoid had been acquired. To investigate potential mechanisms of clinical resistance to RA, we serially evaluated the clinical pharmacology of the drug in APL patients treated with this agent. Leukemic cells from patients relapsing from RA treatment were cultured in the presence of RA and examined for evidence of morphologic maturation. We also studied messenger RNA expression of the newly described gene product of the (15;17) translocation in APL, PML/RA receptor-alpha (PML/RAR alpha). Serial pharmacokinetic studies showed that continuous daily RA treatment was associated with a marked decrease in plasma drug concentrations at the time of relapse compared with the initial day of therapy. Doubling the RA dose in six patients failed to reinduce response at the time of relapse and also failed to significantly augment plasma RA concentrations. However, leukemic cells obtained at the time of relapse from four patients retained in vitro sensitivity to the differentiating activity of RA (10(-6) mol/L). No change was observed in the pattern of PML/RAR-alpha expression assessed by Northern blot analysis at the time of relapse compared with pretreatment in two patients who were tested. These results indicate that clinical relapse and "resistance" to continuous treatment with all-trans RA in APL is associated with progressive reduction of plasma concentrations, potentially to levels below those that sustain differentiation of leukemic cells in vivo. Long-term success of this treatment will require the development of strategies that circumvent this pharmacologic phenomenon. PMID- 1309669 TI - Autologous transplantation of canine long-term marrow culture cells genetically marked by retroviral vectors. AB - Retroviral infection of bone marrow cells in long-term marrow cultures (LTMCs) offers several theoretical advantages over other methods for gene transfer into hematopoietic stem cells. To investigate the feasibility of this approach in a large animal model system, we subjected LTMCs from nine dogs to multiple infections with retrovirus containing the neomycin phosphotransferase gene (neo) during 21 days of culture. Feeder layers, cocultivation, polycations, and selection were not used. The in vitro gene transfer efficiency was 70% as determined by polymerase chain reaction amplification of neo sequences in colony forming unit granulocyte-macrophage (CFU-GM) obtained from day-21 LTMCs. Day-21 LTMC cells were infused into autologous recipients with (four dogs) and without (three dogs) marrow-ablative conditioning. At 3 months posttransplant, up to 10% of marrow cells contained the neo gene. This percentage declined to 0.1% to 1% at 10 to 21 months posttransplant. Neo was also detected in individual CFU-GM, burst forming unit-erythroid (BFU-E), and CFU-Mix progenitors derived from marrow up to 21 months postinfusion and in cultures of peripheral blood-derived T cells up to 19 months postinfusion. There was no difference in the percentage of neo-marked cells present when dogs that received marrow ablative conditioning were compared with dogs receiving no conditioning. Detection of neo-marked marrow cells almost 2 years after autologous transplantation in a large mammalian species shows that retroviral infection of marrow cells in LTMCs is a potentially nontoxic and efficient protocol for gene transfer. Further, our results suggest that marrow conditioning and in vivo selection pressure to retain transplanted cells may not be absolute requirements for the retention of genetically marked cells in vivo. PMID- 1309670 TI - Changing antigen receptor gene rearrangements in a case of early pre-B cell leukemia: evidence for a tumor progenitor cell with stem cell features and implications for monitoring residual disease. AB - A case of acute lymphoblastic leukemia (ALL) was encountered in which the two clonal gamma T-cell receptor gene (TCR gamma) rearrangements found in bone marrow (BM) samples at relapse both differed from the single clonal TCR gamma rearrangement present in BM obtained at diagnosis 5 years previously. In contrast, two clonal Ig heavy chain gene (IgH) rearrangements present at relapse were identical to those present at diagnosis. Comparison of the DNA sequences of the relapse TCR gamma rearrangements with that of the diagnostic TCR gamma rearrangement indicated that they must have been generated de novo from TCR gamma loci in germline configuration. By polymerase chain reaction using clonotypic N region oligonucleotide primers (N-PCR), cells bearing the diagnosis or relapse TCR gamma rearrangements were undetectable in the sample from the opposite time point. Two BM samples obtained at different times in clinical remission were both devoid of detectable residual tumor when analyzed by N-PCR, indicating a depth of remission of less than 1 tumor cell per 4 x 10(5) BM mononuclear cells. The tumor cells showed a primitive phenotype: T-cell antigen-negative, CALLA/CD10-negative, CD20-negative, CD19-positive, and positive for the myeloid marker My9. This case, which appears to represent a tumor arising from a progenitor cell with both early B-lineage and certain stem cell features, has implications for monitoring residual ALL and possibly also for treatment of the disease. PMID- 1309671 TI - Delta-thalassemia due to a mutation in an erythroid-specific binding protein sequence 3' to the delta-globin gene. AB - We have previously described a family of Northern Sardinian descent in which the propositus was affected by thalassemia major resulting from compound heterozygosity for codon 39 nonsense mutation and the beta +IVS II nt 745 mutation and in which all heterozygotes for the beta +IVS II nt 745 mutation had normal hemoglobin (Hb) A2 levels. To define the reasons for normal HbA2 levels in otherwise typical beta-thalassemia heterozygotes, we cloned and sequenced the delta-thalassemia gene in cis to the beta +IVS II nt 745 mutation. The sequence analysis showed a single nucleotide substitution (G----A) at position 69 nts (delta +69) downstream to the polyA addition site. Dot blot analysis with an oligonucleotide probe complementary to the delta +69 mutation detected this mutation in several heterozygotes for the beta +IVS II nt 745 mutation from the proband's family, but failed to show it either in a group of normal individuals of the same origin or in nonrelated heterozygotes for the beta +IVS II nt 745 mutation of the same or different descent from the proband. The delta +69 (G--- A) mutation may be responsible for the low delta-globin output from the beta +IVS II nt 745 chromosome or could be a silent polymorphism not affecting the function of the delta-globin gene. The normal G at position 69 is part of a sequence very similar to the core DNA (A/T)GATA(A/G) motif (GATA box) that is a binding site for the GATA-1 protein. Gel-retardation assay has shown that a DNA fragment containing the GATA motif with the G----A at position +69 has increased binding affinity for erythroid-specific DNA binding protein(s) as compared with the wild type sequence. These findings may suggest that the delta +69 mutation is responsible for the deficient function of the in cis delta-globin gene. PMID- 1309672 TI - Pentoxifylline in treatment of acquired immunodeficiency syndrome? PMID- 1309673 TI - Polyclonal origin of rheumatoid synovial T-lymphocytes. AB - Nineteen T-cell clones from seven patients with RA were obtained by cloning infiltrating lymphocytes from needle synovial biopsies. Southern blot analysis of the T-cell receptor (TCR) beta-chain genes in these clones revealed that there were no T-cell clones with an identical rearrangement of the TCR beta gene. These results do not support the idea that the infiltrating T-lymphocytes in RA are of monoclonal or oligoclonal origin. PMID- 1309674 TI - Intraductal carcinoma of major salivary gland. AB - The clinicopathologic features of the cases of three patients with intraductal carcinoma of major salivary gland are described. As in the breast, these lesions of salivary ducts appear to represent an in situ or preinvasive phase of the disease. On follow-up, one patient had a local recurrence, and in another patient, the tumor subsequently became invasive. This experience suggests that wide surgical excision (preferably total parotidectomy) may be curative but that resections limited to grossly visible disease will result in local recurrence and/or the development of invasive ductal adenocarcinoma. PMID- 1309675 TI - Nucleotide sequence of prothrombin gene in abnormal prothrombin-producing hepatocellular carcinoma cell lines. AB - A protein induced by vitamin K absence or antagonist II, PIVKA-II is synthesized in the liver and possesses a structure similar to prothrombin except that ten glutamic acid residues in amino-terminal Gla domain are not completely gamma carboxylated and are functionally inactive. This protein can be detected in the plasma of patients with hepatocellular carcinoma (HCC) and used as a new tumor marker. To analyze the mechanism of PIVKA-II production in HCC tissue, the prothrombin gene of PIVKA-II-secreting HCC cell lines was sequenced to detect the mutation in the Gla domain and carboxylase recognition site of leader sequence located on exons I and II that may cause the inhibition of carboxylation. Exons I and II and donor and acceptor site of intron I of the prothrombin gene in two HCC cell lines, PLC/PRF/5 and huH-2, were analyzed by polymerase chain reaction (PCR), and the product was sequenced directly. In addition, RNA samples of these cell lines were used for complementary DNA synthesis, followed by PCR and sequencing. The nucleotide sequences of the Gla domain in both HCC cell lines were conserved. One nucleotide change was detected at nt.554 (adenine to guanine), but this did not influence the amino acid sequence. Splicing sites between exons I and II, the leader sequence of the precursor prothrombin, and protease target sites also were conserved as the reported prothrombin gene, and mutations reported for other des-gamma-carboxy coagulation factors were not detected. These results also were confirmed by DNA analysis of seven human fresh frozen samples (three PIVKA-II-positive HCC samples and four control specimens). The mechanism of PIVKA-II production in HCC is still unclear, but it is not caused by mutation in the prothrombin gene. PMID- 1309676 TI - Intraductal carcinoma of the pancreas. AB - Four multicentric intraductal papillary carcinomas arising in the main pancreatic duct are presented. Three of the neoplasms showed stromal invasion and metastasized to regional lymph nodes. Three patients had a long history of epigastric pain, confirming the progressive slow growth and less aggressive nature of this clinicopathologic entity. Histologically, all tumors were papillary, and three also showed a pseudocribriform pattern. Individual cells exhibited a range of atypia from mild to overt malignant change. Focal intestinal differentiation was recognized in two tumors. Despite the well-differentiated appearance of these tumors, two patients died within 1 year of surgery. One patient with an entirely intraductal carcinoma is alive and well 3 years after surgical treatment. The fourth patient who had lymph node metastasis is alive 6 months after a Whipple's procedure. PMID- 1309677 TI - Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer. AB - From December 1987 through April 1989, 40 patients with extensive-stage small cell carcinoma of the lung were enrolled in a Hoosier Oncology Group (HOG) trial using etoposide, ifosfamide, and cisplatin (VIP). Patients with extensive disease were eligible if they had not received prior chemotherapy, had a Karnofsky performance status of 50 or more, and had adequate renal function (creatinine, less than 1.5 mg/dl) and bone marrow reserve (granulocyte count, greater than or equal to 2500/microliters; platelets, greater than or equal to 125,000/microliters). Doses of therapy were: etoposide 75 mg/m2/day on days 1 to 5, ifosfamide 1.2 g/m2/day on days 1 to 5, and cisplatin 20 mg/m2/day on days 1 to 5. The first 11 patients received a 5-day course; this was repeated every 21 days for four cycles, but therapy was shortened to 4 days when unacceptable toxicity was noticed in these patients. Overall, 14 (37%) had a complete remission (overall response rate, 71.1%) with a median survival of 42 weeks (28 weeks on 5-day regimen and 45 weeks on 4-day regimen). There were five early deaths. Although toxic, VIP produces a high complete remission rate in patients with extensive disease and warrants further evaluation. A prospective randomized trial comparing cisplatin and etoposide to the VIP regimen is underway through HOG. PMID- 1309678 TI - Comparison of OK-432 and mitomycin C pleurodesis for malignant pleural effusion caused by lung cancer. A randomized trial. AB - A prospective randomized study to compare the effectiveness of pleurodesis by two new sclerosing agents: OK-432 and mitomycin C were conducted in 53 patients with malignant pleural effusion caused by lung cancer. None of the patients received concomitant systemic chemotherapy or radiation therapy during the study. After complete drainage of pleural fluid, the patients were allocated randomly to receive 10 Klinische Einheit units of OK-432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals. The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures. There were 26 patients who received pleurodesis with OK-432 and 27, with mitomycin C. Patient characteristics in the two treatment groups (age, sex, histologic type, performance status, and prior treatment before pleurodesis) were compatible. These results showed that pleurodesis with OK-432 achieved a higher complete response rate (73%) than that of mitomycin C (41%). The rates of objective treatment response (complete response plus partial response) were comparable in both groups (88% for OK-432 and 67% for mitomycin C). The average number of intrapleural injections needed to achieve complete response was fewer in the OK-432 group (1.9 +/- 0.9) than in mitomycin C group (2.8 +/- 0.9). There was no significant difference in the median survival of the patients who received pleurodesis with OK-432 (5.8 months) or mitomycin C (5.1 months). However, the effusion-free period in the OK-432 group was significantly longer than that in the mitomycin C group (7.0 months versus 1.5 months). Patients who underwent OK 432 pleurodesis had a higher complication rate (80%) than did those in the mitomycin C group (30%). Transient febrile reaction was the most common reaction encountered. The immunologic study in OK-432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio. The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio. It was concluded that pleurodesis with OK-432 is an effective alternative treatment for malignant effusion in patients with lung cancer. PMID- 1309679 TI - Occurrence of human papillomavirus DNA in primary lung neoplasms. AB - The occurrence of human papillomavirus (HPV) DNA in primary lung carcinomas and in squamous metaplasia of the bronchus was studied using in situ hybridization techniques and commercially available biotinylated DNA probes to HPV subtypes 6/11, 16/18, and 31/33/35. The authors found HPV DNA in six of 20 cases of squamous cell carcinoma and one of six cases of large cell undifferentiated carcinoma. There were two cases each of the 6/11 serotypes and the 16/18 serotypes and three cases of the 31/33/35 serotypes. Infected cells of the squamous carcinomas uniformly showed koilocytosis. No case of adenocarcinoma, bronchioloalveolar carcinoma, or small cell carcinoma was positive (of 32 cases). Areas of squamous metaplasia in infected tumors showed similar HPV DNA expression in 15% of cases, especially in those with condylomatous atypia. In 5.8% of random bronchial biopsies of squamous metaplasia, HPV DNA was identified. The relationship of HPV infection to the development of upper and lower respiratory tract carcinomas is discussed. PMID- 1309680 TI - Characterization and comparison of two newly established Epstein-Barr virus (EBV) negative and EBV-positive Burkitt's lymphoma cell lines. EBV-negative cell line with a low level of expression of ICAM-1 molecule and EBV-positive cell line with a high level of expression of ICAM-1 molecule. AB - Two human Burkitt's lymphoma cell lines (HBL-4 and HBL-5) were established individually from two patients with small noncleaved cell lymphoma (Burkitt's type). The HBL-4 cell line is Epstein-Barr virus (EBV)-negative, and the HBL-5 cell line is EBV-positive. Cytogenetically, both cell lines had the same chromosomal translocation, t(8;14)(q24;q32) as those observed in the primary malignant cells from individual patients. Morphologic, immunophenotypic, cytogenetic, and molecular studies confirmed that both cell lines were derived from the primary lymphoma cells in vivo. HBL-4 cells lacked CD23(H107), CD11a(LFA 1), and latent membrane protein (LMP) but expressed CD54(ICAM-1) at low levels, whereas HBL-5 cells showed the high level of expression of CD54 and faint expression of LMP but lacked CD11a. In addition, the EBV-positive lymphoblastoid cell line (LCL) expressed CD11a, CD23, CD54, and LMP at high levels. Therefore, an HBL-5 phenotype with expression of CD54 and LMP tends toward an LCL phenotype, and the augmentation of CD54 on the HBL-5 cells in comparison with primary lymphoma cells is likely to be upregulated by LMP, probably resulting from the EBV infection. There was little difference in the BrdUrd uptake in vivo and in vitro, doubling time, tumorigenicity, and dynamics of tumor growth in athymic nude mice between both cell lines. These findings indicate that the potentiality of cell growth and tumorigenicity of these two cell lines are unlikely to be related with EBV. PMID- 1309681 TI - Treatment of metastatic chemodectoma. AB - Six patients were treated for metastatic chemodectoma at Memorial Sloan-Kettering Cancer Center from 1971 through 1988. Four patients' primary tumors arose in the cervical region, and two arose in the retroperitoneum. Four patients received a total of eight different chemotherapeutic regimens, including cisplatin, doxorubicin, cyclophosphamide, and dacarbazine. Metastatic sites treated included bone, liver, lung, and retroperitoneum. No patient had a response to chemotherapy. Four patients received a total of nine courses of radiation therapy for palliation of bone metastases. Pain relief was complete in eight patients and partial in one. One patient was irradiated for a mass in the left psoas muscle, with stabilization of disease for 6 months after treatment. One patient was irradiated for epidural compression at T6, with resolution of neurologic symptoms and 50% clearing of the spinal block on follow-up myelogram. Recurrence or progression of disease in a previously irradiated site occurred in one patient 2 years after treatment. One patient was lost to follow-up 3 months after radiation therapy for epidural compression. The other five patients died of widespread metastatic disease 6 months to 9 years after initial treatment for their metastatic disease. PMID- 1309682 TI - The use of nuclear morphometry to predict response to therapy in Wilms' tumor. AB - Using nuclear morphometric analysis, a retrospective study was made of 27 patients with Wilms' tumor. The blinded group consisted of 17 patients with Stage I and II favorable-histology Wilms' tumors who did not respond to therapy and ten patients with Stage III and IV favorable-histology Wilms' tumors who did respond. In this complex group of patients, multivariate analysis (with several morphologic descriptors) was used to predict which patients responded to therapy. No single-shape descriptor predicted the response to therapy (P greater than 0.5). However, three shape descriptors: maximum ellipticity (ME), standard error of bending energy (SEBE), and the range of chain code-maximum peak (RCCM), with the multivariate formula of (1131 x SEBE) + (-7 x ME) + (50 x RCCM) + 7.18, separated the two groups (P less than 0.004). This result was statistically significant. Using this multivariate equation and a cutoff value of 0.6 units, this test yielded a sensitivity of 94% and a specificity of 70%. This result, in a complex group of patients, suggests that nuclear morphometry may be useful in the initial assessment of patients with Wilms' tumor and warrants further analysis. PMID- 1309683 TI - Human herpesvirus-6: tumorigenicity and tumor infiltrating lymphocytes. AB - We previously reported that human herpes-virus-6 (HHV-6) genome (strain GS) and a cloned subfragment (pZVH14) transfected NIH 3T3 cells, induced foci of transformation with a frequency significantly above the background level. The transformed cells produced tumors in nude mice and immunocompetent (Swiss) mice. In the current study, nude mice tumors were passed into Swiss mice and more aggressive tumors (G-2TS and 14-2TS derived from HHV-6 genome and pZVH14 DNA, respectively) were produced. 14-2TS tumors caused lung metastasis upon intravenous injection. In the case of subcutaneously growing aggressive tumors, tumor infiltrating lymphocytes (TIL) were isolated and characterized as T cells but lacked tumor specific killing as monitored by 51Cr-release assays. TIL lost activity at day 52 in a 4 h assay (but not in a 19 h assay) against the autologous tumor, but not a Maloney virus induced tumor (Yac-1). These studies indicate that an established nontumorigenic fibroblast cell line, when transfected with pZVH14 DNA of HHV-6, acquires both tumorigenic and metastatic potential and tumor bearing hosts mount immune response against such tumors. PMID- 1309684 TI - Pristane induced gene activation. AB - Studies were performed to examine the effects of 2,6,10,14-tetramethyl pentadecane (pristane) versus 12-O-tetradecanoylphorbol 13-acetate (TPA) on the activation of the CAT gene under the regulatory control of viral promoter/enhancer elements transfected into NIH-3T3, CV-1 and COS-7 cells. The results of these studies demonstrated that (1) pristane or TPA induced trans activation of SV2cat, HIVcat, RSVcat and MMTVcat in cells transfected with each respective plasmid construct, (2) only pristane induced activation of pA10cat and pOSP/11 and (3) neither TPA nor pristane trans-activated pSV0cat. Furthermore, treatment with either pristane or TPA elicited changes in the morphology of each of the cell lines. Collectively these results indicate that pristane is a potent inducer of gene expression and exhibits similar characteristics as the tumor promoter, TPA. PMID- 1309685 TI - Cigarette smoke-induced DNA damage in cultured human lung cells: role of hydroxyl radicals and endonuclease activation. AB - Cigarette smoke can cause DNA single strand breaks in cultured human lung cells (T. Nakayama et al., Nature, 314 (1985) 462-464) but the mechanisms behind this DNA damage have not been clearly elucidated. In the present study we have investigated the possibility that one of the major constituents in cigarette smoke, hydroquinone, may be important for mediating smoke-induced DNA damage in the human epithelial lung cell line, A 549, and the mechanisms behind this damage. Cells were exposed to cigarette smoke, hydrogen peroxide, or hydroquinone, in the absence and presence of different inhibitors, and the resulting DNA damage was assessed either as DNA single strand break formation or formation of the oxidative DNA adduct, 8-hydroxydeoxyguanosine. It was found that (i) exposure to cigarette smoke, hydrogen peroxide or hydroquinone causes a rapid decrease in the intracellular thiol level and a considerable DNA single strand break formation, (ii) the formation of DNA single strand breaks in cells exposed to cigarette smoke is inhibited by catalase, dimethylthiourea, and o phenantroline, suggesting that hydroxyl radicals generated from iron-catalyzed hydrogen peroxide dissociation are involved in the DNA damage, (iii) hydroquinone causes considerable DNA strand break formation that is blocked by aurintricarboxylic acid, an inhibitor of endonuclease activation, and by BAPTA, an intracellular calcium chelator, (iv) addition of hydroquinone to a smoke condensate greatly enhances its ability to cause DNA single strand breaks, and (v) smoke, but not hydroquinone, causes formation of 8-hydroxydeoxyguanosine, a DNA damage product induced by the action of hydroxyl radicals on the DNA base, deoxyguanosine. These findings suggest that the ability of cigarette smoke to cause DNA single strand breaks in cultured lung cells is due to mechanisms involving hydroxyl radical attack on DNA and endonuclease activation. They also suggest that hydroquinone is an important contributor to the DNA damaging effect of cigarette smoke on human lung cells. PMID- 1309686 TI - Inhibition of microsomal glucose 6-phosphatase by unsaturated aliphatic aldehydes and ketones. AB - Aldehydes and ketones with one double bond conjugated to the carbonyl group inhibited the enzyme glucose 6-phosphatase, which is embedded in the microsomal membrane. The Michaelis constant, Km and the maximal rate of reaction, V, were affected in a way dependent on the inhibitor's chain-length: trans-2-pentenal and 1-penten-3-one increased Km linearly with concentration and had almost no effect on V, whereas trans-2-nonenal caused a large increase in V but only a small and non-linear change in Km. The effect of the short-chain aldehydes on the kinetic parameters increased with chain-length, but pentenone increased Km more than did trans-2-heptenal and conjugated dienals did not act as inhibitors. Therefore, sterical effects apparently are of importance. Washing the microsomes after incubation with hexenal or heptenal did not substantially decrease the inhibition, but with nonenal the inhibition was reduced by washing. Inhibition by the SH-group blocking reagent p-hydroxymercuribenzoate was competitive to inhibition by the alkenals. It is concluded that the alpha-beta unsaturated oxo compounds inhibit glucose 6-phosphatase by binding covalently to an important mercapto group and that perturbation of the enzyme's membrane environment also plays a part in the inhibition. PMID- 1309687 TI - Embryolethality and induction of 7-ethoxyresorufin O-deethylase in chick embryos by polychlorinated biphenyls and polycyclic aromatic hydrocarbons having Ah receptor affinity. AB - The lethality and 7-ethoxyresorufin O-deethylase (EROD)-inducing potency of some individual polycyclic aromatic hydrocarbons (PAHs) and coplanar polychlorinated biphenyls (PCBs) in chick embryos were measured in order to compare the mechanisms of action of these compounds. In previous studies it was found that coplanar PCBs and certain PAHs have a high embryolethality in the chicken and that they induce embryonic EROD activity. Although the most potent PAHs were almost as embryolethal as the PCBs when injected into hens' eggs 72 h prior to measurement, they were considerably less potent EROD inducers. In the present study, three coplanar PCBs (3,3',4,4'-tetrachlorobiphenyl (TCB), 3,3',4,4',5 pentachlorobiphenyl (PeCB) and 3,3',4,4',5,5'-hexachlorobiphenyl (HCB)) and four of the most toxic PAHs (benzo[a]anthracene (BaA), benzo[k]fluoranthene (BkF), indeno[1,2,3-cd]pyrene (IP) and dibenzo[a, h]-anthracene (DBahA] were administered to chick embryos in different ways, including co-administration. Additive embryolethality was found when BkF and PeCB were co-administered as well as when BaA and DBahA were given simultaneously. The PAHs were more effective as EROD inducers when injected on day 9 (24 h prior to measurement) than when injected on day 7 (72 h prior to measurement). The opposite was found for PeCB and HCB, whereas no difference in potency was noted when comparing TCB injected 24 and 72 h before EROD determination. These substance-related differences were probably due, at least partly, to differences in biotransformation rates. EROD activities found after treatment with high doses of BkF, IP, or DBahA on day 9 were similar to those measured after treatment with PeCB in doses high enough to give maximal induction. Co-administration of high doses of BkF and PeCB did not further increase the activity, indicating that the PAHs and coplanar PCBs induce EROD to a common maximal value. To decrease the influence of metabolization of the PAHs on their EROD-inducing potency, EROD was determined early in development (day 8) and soon after treatment (24 h) in one experiment. In that experiment, the PAHs proved to be only a few times less potent EROD inducers in relation to their embryolethalities compared with the PCBs. The results of the present study, a previously observed similarity in pathology between chick embryos treated with PAHs and embryos treated with coplanar PCBs, and the fact that the most toxic PAHs also are the most avid Ah receptor binders suggest that the coplanar PCBs and the PAHs largely exert their toxicity in chick embryos via an Ah receptor mediated mechanism. The differences between the compounds in their EROD-inducing potency/embryolethality ratios could probably be explained by their different rates of biotransformation. PMID- 1309688 TI - Recent advances and controversies concerning adnexal neoplasms. AB - This article reviews the diagnostic clinical and histologic features of a group of adnexal tumors, including papillary eccrine adenoma, adenoid cystic carcinoma, Merkel's cell carcinoma, aggressive digital papillary adenoma (and adenocarcinoma), Bowen's disease, intraepidermal epithelioma, microcystic adnexal carcinoma and related tumors, and subcutaneous trichoepithelioma. These are adnexal tumors either often not recognized, because of their rarity, or the origin, biologic potential, and classification of which have been controversial. PMID- 1309689 TI - Didanosine and foscarnet marketed for use by patients with AIDS. PMID- 1309690 TI - In vitro susceptibility and synergy studies of Aspergillus species to conventional and new agents. AB - In vitro susceptibility data using a macrodilution broth method on greater than 100 isolates of Aspergillus spp. are presented. For amphotericin B (Amp B) (n = 105), 67% had minimum inhibitory concentrations (MICs) less than or equal to 2 micrograms/ml, and 90% had MICs less than or equal to 4 micrograms/ml; for 5 fluorocytosine [flucytosine (5FC) (n = 60), 35% had MICs less than or equal to 12.5 micrograms/ml; for miconazole (MCL) (n = 18), 39% had MICs less than or equal to 5 micrograms/ml; for ketoconazole (KTZ) four (13%) of 32 isolates had an MIC less than or equal to 3.1 micrograms/ml; for itraconazole (ITZ) (n = 88), 97% had MICs less than or equal to 6.3 micrograms/ml; and for saperconazole (SAP) (n = 20), 90% had MICs less than or equal to 3.1 micrograms/ml. Of Amp B minimum fungicidal concentrations (MFCs) (n = 25), 76% were less than or equal to 4 micrograms/ml; 5% of ketoconazole (n = 20) and no flucytosine (n = 38) MFCs were less than or equal to 25 micrograms/ml; for itraconazole (n = 60), 70% had MFCs less than or equal to 6.3 micrograms/ml, and for saperconazole (n = 20), 75% had MFCs less than or equal to 3.1 micrograms/ml. Drug interaction studies were also performed. For Amp B and rifampin 36 (92%) of 39 showed synergy, for Amp B and flucytosine six (23%) of 26 showed synergy and another six (23%) showed antagonism; 13 (50%) were indifferent. In five Amp B-itraconazole combination studies, synergy and indifference were seen in two each and an additive effect was observed in one. The published literature on in vitro testing methodology and results for Aspergillus spp. is also reviewed, and recommendations for the clinical use of in vitro susceptibility testing are made. PMID- 1309691 TI - [Thrombosis prevention in outpatients with lower limb injuries]. AB - The antithrombotic effect of a low molecular weight heparin was examined in a prospective randomized trial of 204 outpatients (121 men, 83 women, mean age 34.7 [16-76] years) who required immobilization with a plaster cast because of injury to the lower limb. Subjects in group I (n = 99) received a daily subcutaneous injection (36 mg) of heparin fragment calcium throughout their period in plaster (mean of 15.6 [7-66] days), while group II subjects (n = 105, mean period in plaster 15.7 [7-41] days) acted as untreated controls. Thrombosis was diagnosed by compression sonography, and positive findings were confirmed by phlebography. Thrombosis occurred in 24 patients altogether, 6 in group I (6.1%) and 18 in group II (17.1%) (P less than 0.05). While patients with thromboses had a mean of 1.96 risk factors overall, those in group I had a mean of 2.6 risk factors. Patients without thrombosis had a mean of 1.24 risk factors. The rate of thrombosis was higher in patients with fractures (4 out of 27 in group I; 10 out of 35 in group II) than in those with ligament and soft-tissue injuries (2 out of 72 in group I; 8 out of 70 in group II). The severity of trauma is apparently an important thrombogenic factor.--General thrombo-prophylaxis seems advisable for surgical outpatients requiring immobilisation treatment with a plaster cast. PMID- 1309693 TI - [The indications for surgery in small-cell bronchial carcinoma]. PMID- 1309692 TI - [Herpes simplex-associated exacerbation of Crohn's disease. Successful treatment with acyclovir]. AB - Seven years ago, a now 25-year-old man was found to have Crohn's disease of the terminal ileum as well as of the transverse and sigmoid colon. Despite treatment with both corticosteroids and mesalazine the disease progressed and led to almost complete stenosis of the lumen of the sigmoid colon so that surgical intervention was planned. But because immunohistological examination of the small and large intestinal mucosa had demonstrated herpes simplex virus (HSV I + II) DNA, additional treatment with acyclovir appeared worth-while. The morphological and clinical findings indeed changed decisively, obviating surgery. If a virus infection is found to be a pathogenetic co-factor in a case of Crohn's disease, a therapeutic trial with a suitable antiviral agent seems reasonable. PMID- 1309694 TI - [Early summer meningoencephalitis vaccination. The indications and a critical assessment of the neurological vaccination complications]. PMID- 1309695 TI - A comparative laser-flash absorption spectroscopy study of algal plastocyanin and cytochrome c552 photooxidation by photosystem I particles from spinach. AB - Laser-flash kinetic absorption spectroscopy has been used to compare the rate constants for electron transfer from reduced plastocyanin and cytochrome c552, obtained from the green alga Monoraphidium braunii, to photooxidized P700 (P700+) in photosystem I (PSI) particles from spinach Sigmoidal protein concentration dependence for the observed electron-transfer rate constants are obtained for both proteins. In the absence of added salts, the P700+ reduction rate increases as the pH decreases from approximately 8 to 5.5, then decreases to pH 3.5, this effect being more pronounced with cytochrome c552 than with plastocyanin. At neutral pH, plastocyanin is a more efficient electron donor to P700+ than cytochrome c552, whereas at pH 5.5, which is closer to physiological conditions, the two redox proteins react with approximately equal rate constants. In the presence of increasing concentrations of added salts, the P700+ reduction rate constants for both proteins increase at pH greater than 5.5, but decrease at pH less than 4. At neutral pH, the observed rate constants for both algal proteins have a biphasic dependence on sodium chloride concentration, increasing in a parallel manner with increasing salt concentration, reaching a maximum value at 50 mM NaCl, then decreasing. A similar biphasic dependence is obtained with magnesium chloride, but in this case the maximum value is reached at salt concentrations ten times smaller, suggesting a specific role for the divalent cations in the electron-transfer reaction. PMID- 1309696 TI - Incomplete functional differentiation of HL-60 leukemic cells by synthetic lipopeptides. Partial inhibition by pertussis toxin of enhanced superoxide formation. AB - In human neutrophils, the synthetic lipopeptide, N-palmitoyl-S-[2,3- bis(palmitoyloxy-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-( S)-lysyl-(S) lysyl-(S)-lysine [Pam3CysSer(Lys)4], activates NADPH-oxidase catalyzed superoxide (O2-) formation through pertussis-toxin-sensitive and pertussis-toxin-insensitive mechanisms (Seifert, R., Schultz, G., Richter-Freund, M., Metzger, J., Wiesmuller, K.-H., Jung, G., Bessler, W. G. & Hauschildt, S. (1990) Biochem. J. 267, 795-802). We studied the effects of lipopeptides on differentiation of HL-60 leukemic cells. Pam3CysSer(Lys)4 enhanced phorbol-12-myristate-13-acetate-induced O2- formation (presumably through the expression of components of NADPH oxidase) in a concentration-dependent manner with a half-maximal effect at 100 ng/ml and a maximum at 1 microgram/ml. The effect of the lipopeptide was evident after 24 h and reached a plateau after 48 h. (2S,6S)-2-Palmitoylamino-6,7- bis(palmitoyloxy)heptanoyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S) -lysyl-(S)-lysine enhanced O2- formation as well. The effects of Pam3CysSer(Lys)4 were potentiated by dibutyryl cAMP, dimethyl sulfoxide, retinoic acid, 1,25-dihydroxyvitamin D3, interferon-gamma and tumor-necrosis-factor-alpha. Pertussis toxin, but not its B oligomer, partially inhibited enhanced O2- formation induced by Pam3CysSer(Lys)4. O2- formation induced by arachidonic acid and gamma-hexachlorocyclohexane were more sensitive to inhibition by pertussis toxin than O2- formation induced by phorbol 12-myristate 13-acetate. Enhanced O2- formation induced by dibutyryl cAMP was not affected by pertussis toxin. Unlike ATP, histamine, prostaglandin E1 and the beta-adrenergic agonist, isoproterenol, Pam3CysSer(Lys)4 did not increase cytosolic Ca2+ [( Ca2+]i) in undifferentiated HL-60 cells. Histamine but not lipopeptides stimulated high-affinity GTPase of guanine-nucleotide-binding proteins in membranes of undifferentiated HL-60 cells. In Pam3CysSer(Lys)4 differentiated HL-60 cells, the responsiveness to the [Ca2+]i-increasing agonists, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, C5a and leukotriene B4, was increased, whilst the responsiveness to prostaglandin E1 and isoproterenol was decreased. Pam3CysSer(Lys)4 did not inhibit proliferation of HL-60 cells but decreased transferrin receptor expression and increased C3bi receptor expression. Pertussis toxin did not affect proliferation and expression of transferrin and C3bi receptors. Dibutyryl cAMP was considerably more effective than Pam3CysSer(Lys)4 at inducing alterations in the above parameters. Our results suggest that (a) Pam3CysSer(Lys)4 induces incomplete functional differentiation of HL-60 cells through a mechanism which does not depend on a rise in [Ca2+]i and is different from that of other differentiation-inducing substances and (b) the mechanism by which Pam3CysSer(Lys)4 induces differentiation involves pertussis toxin-sensitive and pertussis-toxin-insensitive mechanisms. PMID- 1309697 TI - Subunits VIIa,b,c of human cytochrome c oxidase. Identification of both 'heart type' and 'liver-type' isoforms of subunit VIIa in human heart. AB - The N-terminal amino acid sequences and the electrophoretic mobilities of the subunits VIIa, VIIb and VIIc of cytochrome c oxidase purified from human heart were investigated and compared with those from human skeletal muscle and from bovine heart. In purified human heart cytochrome c oxidase, both so-called 'heart type' and 'liver-type' isoforms of subunit VIIa were found. The first 30 residues of the N-terminal amino acid sequences of these 'heart-type' and 'liver-type' subunits VIIa showed nine differences. The two isoforms of subunit VIIa in human heart were present in almost equal amounts, in contrast to the situation in skeletal muscle, where the 'heart-type' subunit VIIa was predominant. Therefore, our results imply that in human heart a cytochrome c oxidase isoform pattern is present that differs from that found in skeletal muscle. Subunits VIIb and VIIc purified from human heart oxidase proved to be very similar to their bovine heart counterparts. Our direct demonstration of the presence of subunit VIIb, the sequence of which has only recently been identified in the bovine heart enzyme, suggests that human cytochrome c oxidase also contains 13 subunits. We found no evidence for the presence of different isoforms of subunit VIIc in cytochrome c oxidase from human heart and skeletal muscle. We observed clear differences in the electrophoretic mobility of the subunits VIIa,b,c between bovine and human cytochrome c oxidase. On Tricine/glycerol/SDS/polyacrylamide gels the 'heart type' and 'liver-type' subunits VIIa present in human heart cytochrome c oxidase migrated with almost the same electrophoretic mobility. Subunit VIIb migrated only slightly faster than subunit VIIa, whereas VIIc proved to have the highest electrophoretic mobility on Tricine/SDS/glycerol/polyacrylamide gels. Our findings may have implications for the elucidation of certain tissue-specific cytochrome c oxidase deficiencies in man. PMID- 1309699 TI - Novel excision products of T cell receptor gamma gene rearrangements and developmental stage specificity implied by the frequency of nucleotide insertions at signal joints. AB - We have cloned circular DNA excised by T cell receptor (TcR) gamma 1, gamma 2 and gamma 3 gene rearrangements in fetal and adult mouse thymocytes. Circular DNA contained a signal joint reciprocal to the genomic V-J coding joint. Although signal joints without nucleotide insertions are common in immunoglobulin (Ig) and TcR gene rearrangements, the signal joint of gamma found in adult thymocytes contained non-germ-line element (N) insertions at high frequency, while no insertions were found in fetal thymocytes. Thus developmental stage specificity of TcR gamma gene rearrangements is faithfully reflected on the signal joint of excision products. In addition, examination of gamma gene excision products revealed circular DNA products of TcR gamma-alpha transrearrangements, but no evidence of V gamma gene replacement in a rearranged segment. PMID- 1309698 TI - Mitogen-activated-protein-kinase-catalyzed phosphorylation of microtubule associated proteins, microtubule-associated protein 2 and microtubule-associated protein 4, induces an alteration in their function. AB - Mitogen-activated protein kinase (MAPK), a serine/threonine-specific protein kinase which is generally activated by stimulation with various growth factors and phorbol esters, utilizes microtubule-associated protein (MAP) 2 as a good substrate in vitro. We have found that MAPK-catalyzed phosphorylation of MAP2 resulted in a significant loss in its ability to induce tubulin polymerization. The chymotryptic fragments, containing a microtubule-binding domain of MAP2, were phosphorylated by MAPK and the ability of the fragments to induce tubulin polymerization was also greatly decreased by the phosphorylation, suggesting that phosphorylation of the microtubule-binding domain is important for functional alteration of MAP2. In addition to MAP2, a 190-kDa heat-stable MAP (MAP4) found in various tissues and cells, was a good substrate for MAPK in vitro. Phosphorylation of MAP4 inactivated tubulin polymerization. We examined the effect of phosphorylation of MAP2 and MAP4 on the dynamics of microtubules nucleated by purified centrosomes in vitro. The data showed that MAPK-catalyzed phosphorylation of MAP2 and MAP4 reduced their ability to increase the apparent elongation rate and the number of microtubules nucleated by the centrosome. Thus, MAPK is capable of phosphorylating MAPs and negatively regulating their microtubule-stabilizing function. PMID- 1309700 TI - Differences between T helper cell type I (Th1) and Th2 cell lines in signalling pathways for induction of contact-dependent T cell help. AB - B cells get help in the antibody response by presenting antigen to helper T (Th) cells. Upon antigen recognition, T cells produce lymphokines that act as growth and differentiation factors for B cells, but resting B cells require additional helper signals that depend on cell contact with an activated Th cell. Like lymphokine secretion, contact help must be induced by antigen recognition or antigen receptor cross-linking in continuous Th cell lines. In the mouse, most CD4+ T cell lines can be classified into one of two stable differentiation states, Th1 or Th2, which produce different lymphokines and have different effector functions, activation requirements and cytoplasmic signalling mechanisms. This report demonstrates additional differences between Th1 and Th2 cell lines in the signalling pathways leading from the T cell antigen receptor to the induction of Th functions. In a system dependent on antigen presentation by B cells, B cell proliferation driven by Th2 cells but not Th1 cells was blocked by acute treatment with phorbol esters. Further experiments showed that phorbol esters blocked the induction of both contact help and lymphokine production in Th2 cells but not in Th1 cells. However, depletion of protein kinase C (PKC) activity by prolonged treatment of T cells with high concentrations of phorbol esters blocked induction of contact help and lymphokine production in Th1 cells but not in Th2 cells. These findings support the hypothesis that Th2 cells use a signalling pathway that is independent of PKC and that PKC activation can block this pathway. Since contact help and lymphokine secretion are affected in parallel, this difference between Th1 and Th2 cells probably reflects early events in the signalling pathway. Contact help and lymphokine production could be dissociated with cholera toxin and other cAMP agonists, but this dissociation could be explained by non-cAMP-related effects of cholera toxin on induction of contact help in Th2 cells, and by the direct effect of cAMP agonists on interleukin 2 gene transcription in Th1 cells reported by other laboratories. PMID- 1309701 TI - Schistosoma mansoni: characterization of phosphoinositide response. AB - Signal transduction pathways may have important regulatory roles in cellular events in the human parasite Schistosoma mansoni. The presence of the phosphoinositide response in S. mansoni was examined by radiolabeling intact worms with 20 muCi of [3H]myoinositol for 24 hr and stimulating parasites with 25 mM NaF and 10 microM AlCl3 in the presence of 10 mM LiCl. Total inositol phosphates were increased within 2 min and maximal accumulation was achieved after 30 min. Similar results were seen with the non-hydrolyzable GTP analogues GTP gamma S and GppNHp while only minimal changes were detected with GMP. Neomycin inhibited NaF-induced inositol phosphate production. NaF stimulated a significant 3.6-fold increase of inositol phosphates in females compared to males. These data suggest that stimulation of guanine nucleotide-binding regulatory proteins activates phospholipase C resulting in production of inositol phosphates in S. mansoni. PMID- 1309703 TI - Conformational study of cyclo[D-Trp-D-Asp-Pro-D-Val-Leu], an endothelin-A receptor-selective antagonist. AB - The conformation of cyclo[D-Trp-D-Asp-Pro-D-Val-Leu], (BQ123), an endothelin-A receptor-selective antagonist, has been studied in 20% acetonitrile in water by CD and NMR spectroscopy. CD studies showed the peptide adopted a similar, constrained conformation in both water alone and 20% acetonitrile in water. NMR spectra showed the proline residue to be in the trans conformation and 2 of the NH protons to exchange slowly with the solvent, indicating hydrogen bonding. Structural constraints derived from the NMR spectra were used to define the conformation in molecular dynamics simulations. A single backbone conformation is observed for the cycle, comprising a beta type II turn and a gamma' turn. PMID- 1309702 TI - Trypanosoma cruzi: alteration of cAMP metabolism following infection of human endothelial cells. AB - We have previously reported that Trypanosoma cruzi infection of endothelial cells results in alterations in the metabolism of Ca2+, inositol triphosphate (IP3), and prostacycline (PGI2). In this report, we demonstrate that infection also alters the metabolism of cAMP. Infection of endothelial cells does not significantly alter beta-adrenergic receptor density or affinity, adenylate cyclase activity, and whole-cell cAMP levels. However, incubation of infected endothelial cells with the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) resulted in less than a 60% increase in cell cAMP in contrast to the greater than a 100% increase observed in uninfected endothelial cells under otherwise identical reaction conditions. Infected endothelial cells demonstrated a twofold increase in phosphodiesterase activity when measured directly. Moreover, homogenates prepared from infected endothelial cells previously incubated with isoproterenol for 20 min showed little or no change in PDE activity. In contrast, homogenates prepared from uninfected endothelial cells treated under otherwise identical reaction conditions showed a 5.7-fold increase in PDE activity. In the presence of IBMX, isoproterenol-dependent stimulation of cAMP levels in infected endothelial cells reached a maximum level at 5 min of incubation, and thereafter rapidly declined. In contrast, cAMP levels in uninfected endothelial cells reached a maximum at 2 min of incubation, and thereafter remained elevated throughout the duration of the incubation. Infection associated changes in isoproterenol dependent stimulation of cAMP accumulation appear to relate, in part, to changes in PDE activity. PMID- 1309704 TI - Opioid peptides derived from wheat gluten: their isolation and characterization. AB - Four opioid peptides were isolated from the enzymatic digest of wheat gluten. Their structures were Gly-Tyr-Tyr-Pro-Thr, Gly-Tyr-Tyr-Pro,Tyr-Gly-Gly-Trp-Leu and Tyr-Gly-Gly-Trp, which were named gluten exorphins A5, A4, B5 and B4, respectively. The gluten exorphin A5 sequence was found at 15 sites in the primary structure of the high molecular weight glutenin and was highly specific for delta-receptors. The structure-activity relationships of gluten exorphins A were unique in that the presence of Gly at their N-termini increased their activities. Gluten exorphin B5, which corresponds to [Trp4,Leu5]enkephalin, showed the most potent activity among these peptides. Its IC50 values were 0.05 microM and 0.017 microM, respectively, on the GPI and the MVD assays. PMID- 1309705 TI - Effect of glucagon on insulin receptor phosphorylation in intact liver cells. AB - Evidence is presented that incubation of rat liver cells with glucagon leads to an increase in the phosphorylation of specific serine residues within insulin receptors, particularly in the presence of insulin. However, no changes in either the tyrosine phosphorylation of the receptors or the tyrosine kinase activity towards a synthetic peptide substrate was detected. PMID- 1309706 TI - Ca(2+)-dependent ubiquitination of calmodulin in yeast. AB - Recently we were able to show that calmodulin from vertebrates, plants (spinach) and the mold Neurospora crassa can be covalently conjugated to ubiquitin in a Ca(2+)-dependent manner by ubiquityl-calmodulin synthetase (uCaM-synthetase) from mammalian sources [R. Ziegenhagen and H.P. Jennissen (1990) FEBS Lett. 273, 253 256]. It was therefore of high interest to investigate whether this covalent modification of calmodulin also occurs in one of the simplest eukaryotes, the unicellular Saccharomyces cerevisiae. Yeast calmodulin was therefore purified from bakers yeast. In contrast to calmodulin from spinach and N. crassa it does not activate phosphorylase kinase. Crude yeast uCaM-synthetase conjugated ubiquitin Ca(2+)-dependently to yeast and mammalian (bovine) calmodulin. Yeast calmodulin was also a substrate for mammalian (reticulocyte) uCaM-synthetase. As estimated from autoradiograms the monoubiquitination product (first-order conjugate) of yeast calmodulin has an apparent molecular mass of ca. 23-26 kDa and the second-order conjugate an apparent molecular mass of ca. 28-32 kDa. Two to three ubiquitin molecules can be incorporated per yeast calmodulin. Experiments with methylated ubiquitin in the heterologous reticulocyte system indicate that, as with vertebrate calmodulins, only one lysine residue of yeast calmodulin reacts with ubiquitin so that the incorporation of multiple ubiquitin molecules will lead to a polyubiquitin chain. These results also indicate that the ability of coupling ubiquitin to calmodulin was acquired at a very early stage in evolution. PMID- 1309707 TI - Interaction of ACTH, beta-endorphin and alpha-melanocyte stimulating hormone in relation to the corticosteroid production of isolated rat adrenocortical zona fasciculata and zona glomerulosa cells. AB - The combined effects of ACTH, beta-endorphin (beta-EP) and alpha-MSH were studied on the corticosteroidogenesis of isolated rat adrenocortical zona fasciculata and zona glomerulosa cells. beta-EP potentiated the effects of ACTH and alpha-MSH on the zona fasciculata corticosterone production but inhibited those on the zona glomerulosa aldosterone production. beta-EP did not affect the combined action of 4 x 10(-11) M ACTH and 5 x 10(-9) M alpha-MSH on the zona fasciculata or the zona glomerulosa cells, but it inhibited the stimulatory action of the combination of 1.6 x 10(-10) M ACTH and 10(-9) M alpha-MSH on the zona glomerulosa aldosterone production. An interaction of ACTH, beta-EP and alpha-MSH in relation to the zona fasciculata and zona glomerulosa corticosteroid production was found. PMID- 1309709 TI - Assembly of contractile and cytoskeletal elements in developing smooth muscle cells. AB - Specific developmental changes in smooth muscle were studied in gizzards obtained from 6-, 8-, 10-, 12-, 14-, 16-, 18-, and 20-day chick embryos and from 1- and 7 day posthatch chicks. Myoblasts were actively replicating in tissue from 6-day embryos. Cytoplasmic dense bodies (CDBs) first appeared at Embryonic Day 8 (E8) and were recognized as patches of increased electron density that consisted of actin filaments (AFs), intermediate filaments (IFs), and cross-connecting filaments (CCFs). Although the assembly of CDBs was not synchronized within a cell, the number, size, and electron density of CDBs increased as age increased. Membrane-associated dense bodies (MADBs) also could be recognized at E8. The number and size of MADBs increased as age increased, especially after E16. Filaments with the diameter of thick filaments first appeared at E12. Smooth muscle cells were able to divide as late as E20. The axial intermediate filament bundle (IFB) could first be identified in 1-day posthatch cells and became larger and more prominent in 7-day posthatch cells. Immunogold labeling of 1- and 7-day posthatch cells with anti-desmin showed that the IFB contained desmin IFs. The developmental events during this 23-day period were classified into seven stages, based primarily on the appearance and the growth of contractile and cytoskeletal elements. These stages are myoblast proliferation, dense body appearance, thick filament appearance, dense body growth, muscle cell replication, IFB appearance, and appearance of adult type cells. Smooth muscle cells in each stage express similar developmental characteristics. The mechanism of assembly of myofilaments and cytoskeletal elements in smooth muscle in vivo indicates that myofilaments (AFs and thick filaments) and filament attachment sites (CDBs and MADBs) are assembled before the axial IFB, a major cytoskeletal element. PMID- 1309708 TI - Multiple sclerosis, sarcoidosis and other diseases in patients with pars planitis. PMID- 1309710 TI - Regulation of M-phase progression in Chaetopterus oocytes by protein kinase C. AB - We have examined the presence of protein kinase C in oocytes of Chaetopterus pergamentaceus and its role in the initiation of germinal vesicle breakdown (GVBD). First, we demonstrated that the oocytes contain a phospholipid- and calcium-dependent protein kinase, protein kinase C (PKC). Since PKC is the primary intracellular receptor for phorbol esters, we tested the ability of phorbol 12,13-dibutyrate (PDBu) to induce GVBD and compared several critical events and processes involved in GVBD induced by PDBu to those induced normally (by seawater). Seawater and 100-200 nM PDBu induced chromosome condensation, spindle formation, and spindle migration over a similar time course. Both treatments induced similar alterations in the SDS-PAGE pattern of newly synthesized proteins. The synthesis of polypeptides of approximately 46 and 54 kDa increased specifically. Both treatments increased oocyte protein phosphorylation, especially of proteins of 22, 32, 46, 55, 64, and 84 kDa. Both treatments resulted in the activation of an M-phase-specific histone H1 kinase activity, which demonstrates the appearance of maturation-promoting factor. Staurosporine, a potent protein kinase C inhibitor, blocked GVBD and the activation of M-phase-specific H1 kinase, whereas HA1004, which preferentially antagonizes protein kinase A, had no effect. The results of this study demonstrate that protein kinase C can activate a wide spectrum of essential biochemical and morphological processes involved in GVBD. Further, these studies suggest that protein kinase C elicits GVBD by activating maturation-promoting factor and support the hypothesis that protein kinase C plays an essential role in oocyte maturation in this species. PMID- 1309711 TI - Coordinate pretranslational control of cAMP-dependent protein kinase subunit expression during development in the water mold Blastocladiella emersonii. AB - The aquatic fungus Blastocladiella emersonii provides a system for studying the regulation of expression of regulatory (R) and catalytic (C) subunits of cAMP dependent protein kinase (PKA). Blastocladiella cells contain a single PKA with properties very similar to type II kinases of mammalian tissues. During development cAMP-dependent protein kinase activity and its associated cAMP binding activity change drastically. We have previously shown that the increase in cAMP-binding activity during sporulation is due to de novo synthesis of R subunit and to an increase in the translatable mRNA coding for R (Marques et al., Eur. J. Biochem. 178, 803, 1989). In the present work we have continued these studies to investigate the mechanism by which the changes in the level of kinase activity take place. The C subunit of Blastocladiella has been purified; antiserum has been raised against it and used to determine amounts of C subunit throughout the fungus' life cycle. A sharp increase in C subunit content occurs during sporulation and peaks at the zoospore stage. Northern blot analyses, using Blastocladiella C and R cDNA probes, have shown that the levels of C and R mRNAs parallel their intracellular protein concentrations. These results indicate a coordinate pretranslational control for C and R subunit expression during differentiation in Blastocladiella. PMID- 1309712 TI - Acquisition of a transcriptionally permissive state during the 1-cell stage of mouse embryogenesis. AB - Zygotic gene transcription initiates during the 2-cell stage of mouse embryogenesis. To learn more of the nature and timing of events leading up to transcriptional activation, we evaluated the ability of enucleated 1-cell-stage embryos to support transcription of the 2-cell-stage-specific gene(s) encoding the 70,000-Da transcription-requiring complex (TRC). Nuclei were transplanted from transcriptionally inhibited alpha-amanitin or N-[2-(methylamino)ethyl]-5 isoquinolinesulfonamide (H8)-treated 2-cell-stage embryos to either late or early enucleated 1-cell-stage recipients. Expression of the TRC gene(s) was much greater following transfer to late 1-cell than early 1-cell-stage recipients. In addition, treatment of early 1-cell-stage recipients with N6-monobutyryl cyclic AMP following transplantation of a nucleus from an H8-treated donor increased the rate of TRC synthesis to a value similar to that observed for late 1-cell-stage recipients. These results indicate that during the first cell cycle and prior to initiation of zygotic gene expression, the embryonic cytoplasm undergoes a transition from a transcriptionally nonpermissive to permissive state. PMID- 1309713 TI - Coping styles, psychopathology and intellectual performance in patients with familial adenomatous polyposis. AB - Thirty-eight patients with familial adenomatous polyposis (FAP) were compared with 19 patients with ulcerative colitis (UC) for differences in illness-related variables, coping styles, psychiatric symptomatology, and intellectual performance. Patients with FAP had significantly less education, longer time since recent surgery, less psychiatric illness, and evidence of less preoccupation with their illness, as compared with UC patients. FAP patients with a positive family history (N = 28) scored significantly lower on both verbal and performance intellectual tests, even when taking education into account, compared with FAP patients without a family history (N = 9). The relevance of these findings to the ongoing monitoring and surveillance of patients with FAP is discussed. PMID- 1309714 TI - Amino acids necessary for DNA contact and dimerization imply novel motifs in the papillomavirus E2 trans-activator. AB - The bovine papillomavirus E2 protein regulates viral transcription by binding as a dimer to the DNA sequence ACCGN4CGGT. The dimerization and DNA-binding properties are localized within its carboxy-terminal 85 amino acids (325-410). Utilizing random mutagenesis coupled with phenotypic selection in yeast, functionally important amino acids in the DNA-binding domain were identified. Four trans-activation defective point mutants within a short segment (amino acids 337-344) were DNA binding defective but dimeric. The mutation of a conserved tryptophan to serine also eliminated DNA binding, but loss of dimerization was implicated because addition of dimeric monoclonal antibody complemented this defect. A simple assay for E2 dimerization was developed using UV irradiation to produce an interchain cross-link within a dimer. No heterodimeric complexes were formed when pools of E2 of varying lengths were mixed, and only proteins with tryptophan at position 360 could be UV cross-linked. Peptide mapping of irradiated E2 protein localized the cross-link to an 18-amino-acid region bracketing this tryptophan. Substitutions for this tryptophan demonstrated the requirement for a hydrophobic residue at this position, but surprisingly, even alanine was functional. Replacement of this tryptophan with three polar amino acids or glycine eliminated DNA-binding activity, but addition of dimeric monoclonal antibody restored this function. The amino acids that were identified as being involved in DNA contact and dimerization imply that these functions are mediated by novel binding motifs. PMID- 1309715 TI - Ty3 integrates within the region of RNA polymerase III transcription initiation. AB - Over 190 independent insertions into target plasmids of the retrovirus-like element Ty3 were recovered and mapped. Ty3 was shown to insert upstream of tRNA, 5S, and U6 genes, all of which are transcribed by RNA polymerase III. Integration sites were within 1-4 nucleotides of the position of transcription initiation, even for one mutant gene where the polymerase III initiation site was shifted to a completely new context. Mutagenesis of a SUP2 tRNA gene target showed that integration required functional promoter elements but that it did not correlate in a simple way with target transcription. This is the first report directly linking a discrete genomic function with preferential insertion of a retrotransposon. PMID- 1309716 TI - Uterine mullerian adenosarcoma following adenomyoma in a woman on tamoxifen therapy. AB - The clinical and pathologic findings in a 53-year-old woman who developed a uterine adenosarcoma following an adenomyoma are described. During the interval between the diagnosis of adenomyoma and the subsequent diagnosis of adenosarcoma, the patient developed breast carcinoma and received adjuvant chemotherapy that included tamoxifen. The possible stimulatory effects of this drug upon the patient's pre-existing adenomyoma are discussed in view of reports of tamoxifen associated endometrial carcinoma and uterine sarcomas developing in the setting of estrogen excess. PMID- 1309717 TI - Human papillomavirus DNA in women without and with cytological abnormalities: results of a 5-year follow-up study. AB - To determine the prevalence of HPV 6, 11, 16, and 18 in a population without cytological or histological abnormalities, the cervical smears of women attending three clinics in Germany were screened over the past 5 years. The filter in situ hybridization method was used throughout. A total of 20,161 smears, taken from 11,667 women, were tested. When the results of only the first examination are considered, 8.8% (950/10,778) of women with normal cytology were positive for HPV DNA. If we divide the latter into age groups, 11% (852 HPV positive/7716) were below the age of 55 years and 3.2% (98 HPV positive/3062) were above this age. When the samples from patients who had undergone at least two examinations and remained cytologically negative during the 5-year period were examined (total, 2709 women), the HPV DNA positively increased to 34.7% (640/1862) for the sexually active age groups and to 9.0% (76/847) for those above 55 years of age. This study reveals that, although papillomaviral production is most pronounced in younger women, these infections are quite common in all age groups. During the period of investigation, 19 (0.65%) patients, who were diagnosed as cytologically negative at the first examination, progressed to carcinoma in situ or invasive carcinoma. Of these, 63.2% revealed a detectable HPV infection during the study period. The progression of HPV-positive women from normal cytology to CIN or cancer occurred at an annual frequency of 0.082%. With an infected lifespan of 45 years assumed, this results in a lifetime risk of 3.7%. PMID- 1309718 TI - Epinephrine and the genesis of hypertension. AB - Several lines of evidence suggest a psychophysiological link between stress, adrenomedullary activation, and the genesis of hypertension. Experimental data support four important concepts: 1) epinephrine stimulates prejunctional beta 2 adrenergic receptors that facilitate norepinephrine release from sympathetic nerve endings; 2) epinephrine can be converted into a cotransmitter by neuronal uptake and on subsequent release augment the simultaneous discharge of norepinephrine; 3) exogenous epinephrine can induce sustained hypertension in rats; and 4) there is a period of critical sensitivity to endogenous epinephrine in a genetic model of rat hypertension. Plasma epinephrine concentrations are elevated in many young subjects with borderline or mild hypertension. The hypothesis that intermittent surges in epinephrine could initiate or promote the development of primary hypertension by amplifying peripheral neurotransmission, both directly (facilitative effect) and indirectly (cotransmitter action), is supported by reports that hemodynamic and noradrenergic responses to sympathetic activation can be augmented by increases in endogenous epinephrine or by its local or systemic (up to 30 ng/kg/min) infusion. Such responses have been documented in both normotensive and hypertensive subjects and can be blocked by propranolol. Although the weight of evidence (mostly indirect) indicates that epinephrine can augment norepinephrine release in humans, the epinephrine hypothesis, itself, remains unproven. Expression of hypertension by this mechanism may be restricted to a specific epinephrine-sensitive subset of individuals with a genetic predisposition to high blood pressure. PMID- 1309719 TI - Molecular biology of the calcium antagonist receptor. AB - The calcium channel plays a key role in controlling many physiological processes in the body. Drugs that block the calcium channel have proven clinically effective for the treatment of a multitude of cardiovascular disorders. The elucidation of the precise mechanism of action of these drugs involves cloning the calcium channels on which they act. Genetic manipulation of these cloned channels is beginning to reveal the binding sites for the calcium channel blocking drugs and may lead to the development of more specific agents. PMID- 1309720 TI - Identification of a genetic locus essential for capsule sialylation in type III group B streptococci. AB - The type III capsular polysaccharide of group B streptococci (GBS) consists of a linear backbone with short side chains ending in residues of N-acetylneuraminic acid, or sialic acid. The presence of sialic acid on the surface of the organism inhibits activation of the alternative pathway of complement and is thought to be an important element in the virulence function of the capsule. We showed previously that a mutant strain of GBS that expressed a sialic acid-deficient, or asialo, form of the type III polysaccharide was avirulent, supporting a virulence function for capsular sialic acid. We now report the derivation of an asialo capsule mutant from a highly encapsulated wild-type strain of type III GBS, strain COH1, by insertional mutagenesis with transposon Tn916 delta E. In contrast to the wild-type strain, the asialo mutant strain COH1-11 was sensitive to phagocytic killing by human leukocytes in vitro and was relatively avirulent in a neonatal rat model of GBS infection. The asialo mutant accumulated free intracellular sialic acid, suggesting a defect subsequent to sialic acid synthesis in the biosynthetic pathway leading to capsule sialylation. The specific biosynthetic defect in mutant strain COH1-11 was found to be in the activation of free sialic acid to CMP-sialic acid: CMP-sialic acid synthetase activity was present in the wild-type strain COH1 but was not detected in the asialo mutant strain COH1-11. One of the two transposon insertions in the asialo mutant COH1-11 mapped to the same chromosomal location as one of the two Tn916 insertions in the previously reported asialo mutant COH31-21, identifying this site as a genetic locus necessary for expression of CMP-sialic acid synthetase activity. These studies demonstrate that the enzymatic synthesis of CMP-sialic acid by GBS is an essential step in sialylation of the type III capsular polysaccharide. PMID- 1309721 TI - Insertion sequence IS1016 and absence of Haemophilus capsulation genes in the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius. AB - Brazilian purpuric fever (BPF) strains of Haemophilus influenzae biogroup aegyptius form a clone of organisms distinct from more innocuous, conjunctivitis associated isolates. There has been controversy over whether the virulence of BPF strains might derive from the presence of a polysaccharide capsule analogous to that found in conventional invasive H. influenzae, a controversy fuelled by the observation (G. M. Carlone, L. Gorelkin, L. L. Gheesling, A. L. Erwin, S. K. Hoiseth, M. H. O. Mulks, S. P. Connor, R. S. Weyant, J. Myrick, L. Rubin, R. S. Mumford III, E. H. White, R. J. Arko, B. Swaminathan, L. M. Graves, L. W. Mayer, M. K. Robinson, S. P. Caudill, and the Brazilian Purpuric Fever Study Group, J. Clin, Microbiol. 27:609-614, 1989) that a capsulation DNA probe from H. influenzae type b hybridized uniquely to BPF strains. In this work, the basis for this hybridization has been established as the possession by BPF strains, but not by non-BPF strains, of the Haemophilus insertion element IS1016. Although IS1016 is associated with the capsulation locus in some Haemophilus spp., a Southern hybridization study suggests that in BPF strains there are no capsulation genes. PMID- 1309722 TI - Molecular cloning of the recA gene and construction of a recA strain of Francisella novicida. AB - A gene locus that is functionally analogous to the recA gene of Escherichia coli was molecularly cloned from Francisella novicida. The cloned gene was found to suppress the sensitivity of an E. coli strain to DNA-damaging agents and to support genetic recombination in E. coli. After transposon mutagenesis, the recA like gene locus was returned to F. novicida and a UV-sensitive F. novicida strain was isolated. In contrast to the wild-type strain, this UV-sensitive strain could not be transformed with chromosomal DNA. PMID- 1309723 TI - Role of superoxide dismutase in resistance of Porphyromonas gingivalis to killing by polymorphonuclear leukocytes. AB - Porphyromonas gingivalis in which the synthesis of superoxide dismutase (SOD) was induced by nitrate or by aeration was rendered resistant to killing by polymorphonuclear leukocytes. SOD purified from either anaerobically maintained or aerated cells also inhibited bacterial killing when added exogenously, and no difference between the effects of the two SODs was observed. These results suggest that SOD may form part of a defense mechanism that helps protect P. gingivalis against killing by polymorphonuclear leukocytes. PMID- 1309724 TI - Detection of human papillomavirus DNA sequences in tongue squamous-cell carcinoma utilizing the polymerase chain reaction method. AB - Twenty-four cases of tongue squamous-cell carcinoma (SCC) were analyzed for human papillomavirus (HPV) DNAs by the polymerase chain reaction (PCR) method and the dot-blot hybridization technique. HPV DNAs were detected in 8 cases. One specimen histopathologically diagnosed as poorly differentiated grade-III SCC contained both HPV-16 and HPV-18 DNA, and 7 other cases contained HPV-16 DNA. PMID- 1309725 TI - Spontaneous metastatic potential of rat hepatocarcinoma cells after cell fusion or DNA transfection. AB - Eight LF x ICIG cell hybrid clones, isolated upon fusion of normal ICIG-7 human fibroblasts with tumorigenic, non-metastatic LF Cl.2A cells derived from a DAB induced rat hepatocarcinoma, were studied. They were all highly tumorigenic and were capable of developing spontaneous lung metastases in syngeneic animals. All the hybrids were characterized by a rapid loss of human chromosomes. However, in long-term culture, they all revealed a persistence of human genetic information as assessed by Southern blotting. In hybrid lines in which human chromosomes were still visible, the most recurrent were numbers 7 and 9. Neither chromosome 7, previously reported to bear some of the genes controlling metastasis in human X mouse T-cell hybrids, nor chromosome 9 appeared to be correlated with the metastatic potential of LF X ICIG hybrids. The same conclusion applied (1) to a human 3.3-kb EcoRI DNA fragment which was amplified (approx. 10-fold) only in metastases induced by one out of 3 metastatic hybrids tested; (2) to the transcription level of c-Ha-ras and c-Ki-ras genes which was enhanced (approx. 4 fold) in metastatic and non-metastatic lines as well. Co-transfection of LF Cl.2A cells with pHSG 272 selectable marker DNA and genomic DNA from normal ICIG-7 human cells or from a hybrid-induced metastasis, reproducibly gave rise to geneticin-resistant transfectants capable of producing spontaneous lung metastases. Neither transfectants nor transfectant-induced metastases harbored detectable human DNA sequences but all harbored pHSG 272 DNA. These results again call for caution in gene transfer studies of the metastatic process. PMID- 1309726 TI - Local growth of a Burkitt's lymphoma versus disseminated invasive growth of the autologous EBV-immortalized lymphoblastoid cells and their somatic cell hybrids in SCID mice. AB - Specific host-graft interactions, as well as intrinsic properties of transferred cell, determine tumorigenicity in xenogeneic systems. We compared the growth characteristics of human B-lymphoid cell lines in SCID mice with the well characterized growth pattern in nude mice and observed striking differences in malignancy in the respective hosts. Two cell lines derived from the same individual, the Epstein-Barr-virus(EBV)-positive Burkitt's lymphoma BL 60 (BL) and the autologous EBV-immortalized lymphoblastoid cell line IARC 277 (LCL) were used. In addition, we tested somatic cell hybrids (HYB) of both cell lines, which despite the LCL-like differentiation phenotype show the de-regulated c-myc expression pattern of the parental BL line, assumed to be a critical factor in BL pathogenesis. Subcutaneously (s.c.) injected BL cells produced local progressively growing tumor masses at the injection site without distant metastases in both nude and SCID mice. Although both mouse strains possess the same genetic background (BALB/c) and differ only in the B-cell sub-set, the growth patterns of the LCL and hybrids were completely different. In contrast to the regressive behaviour of LCL and hybrids in nude mice, these lines show invasive and disseminated progressive growth in SCID mice. Peripheral lymph nodes an thymic tissue were preferentially colonized, whereas mucosal-associated lymphoid tissue (Peyer's patches and appendix) and spleen were not infiltrated. The preferential migration of lymphocytes to certain tissues is termed homing in a syngeneic system and mediated by homing receptors and vascular addressins. The "homing" of LCL and hybrids into lymphoid SCID mouse tissue suggests a strong interaction with the endothelial cells of the host. Detailed phenotypic analysis of BL, LCL and 3 different hybrids was performed using an antibody panel against differentiation and adhesion markers. Overall dominance of the LCL phenotype was observed in the hybrids, as indicated by cytology, tumor growth, dissemination and the pattern of surface-marker expression. The c-myc activation in hybrids does not appear to influence growth behavior. PMID- 1309727 TI - Ouabain-sensitive Na-K ATPase response in the rabbit iris-ciliary body after lensectomy-vitrectomy. AB - We studied ouabain-sensitive Na-K adenosine triphosphatase (ATPase) activities in the iris-ciliary body of rabbit eyes after lensectomy-vitrectomy. Changes in enzyme activities were quantitatively investigated in the plasma membrane of iris ciliary body at 0 or 7 hours and at days 1, 3, 7, and 14. The specific activity of Na-K ATPase rose to significantly higher levels than the control value at 7 hours following surgery, but returned to the baseline value after 7 days. In addition, we evaluated enzyme activities after lensectomy-vitrectomy during which SF6 or silicone oil was injected. The specific activity of Na-K ATPase following the injection of SF6 or silicone oil was significantly higher than the control value at 7 hours and did not return to the normal value even after 14 days. Consensual reaction, demonstrated by increased Na-K ATPase activity, also was found in the contralateral unoperated eyes of SF6- and silicone oil-injected rabbits. The increased Na-K ATPase activity in the iris-ciliary body after experimental surgery may play an important role in restoring swollen tissues. PMID- 1309728 TI - Human papillomavirus DNA in tissues and ocular surface swabs of patients with conjunctival epithelial neoplasia. AB - DNA from human papillomavirus (HPV) type 16 has been recently identified in conjunctival epithelial dysplasia and carcinoma. In other body sites, HPV 16 is thought to play a role in the development of dysplastic lesions. To further explore the relationship between HPV and conjunctival neoplasia, we examined paraffin-embedded tissue samples from 42 biopsies or excisions from 38 patients whose lesions ranged from mild dysplasia to infiltrating squamous carcinoma of the conjunctiva. We also examined limbal swabs from six patients with dysplasia or carcinoma, five of whom also had tissue samples available for study. HPV 16 DNA was present in 37 (88.1%) tissue samples, including duplicate samples from four patients. Five (83.3%) of six patients who had conjunctival swabs had HPV 16 DNA present in the swabs, including two patients whose lesions had been excised one and eight years before swabs were done. We conclude there is a high prevalence of HPV 16 DNA in conjunctival epithelial neoplasia, suggesting that the development of neoplasia is related somehow to the presence of this virus. However, based on its presence in clinically uninvolved eyes and on the persistence of infection many years after successful eradication of the lesions, HPV apparently does not act alone in the development of conjunctival epithelial neoplasia. PMID- 1309729 TI - Ultrastructural localization of Na+, K(+)-ATPase in the exorbital lacrimal gland of rat. AB - Ultrastructural localization of Na+, K(+)-ATPase in the exorbital lacrimal gland of rat was investigated quantitatively by protein A-gold technique. Na+, K(+) ATPase was purified from the rat kidney, and anti-holo Na+, K(+)-ATPase antibody was obtained from the rabbit by injecting the purified enzyme. A specific antibody against the alpha-subunit of Na+, K(+)-ATPase was affinity purified. Immunoblot analysis revealed that the antibody bound specifically to the alpha subunit of Na+, K(+)-ATPase of the lacrimal gland. Rats were fixed by perfusion with 4% paraformaldehyde containing 1% glutaraldehyde, and the lacrimal glands were embedded in LR White resin. Ultrathin sections were incubated with affinity purified antibody against the alpha-subunit of Na+, K(+)-ATPase, and then with protein A-gold complex. The sections were observed under an electron microscope. Light microscopy with silver enhancement procedure revealed that Na+, K(+)-ATPase was located mainly on the basal region of the cells of intralobular and interlobular ducts. Quantitative immunoelectron microscopic analysis showed that gold particles were found on the basolateral surfaces of the interlobular and intralobular ducts cells and on the basolateral surface of the acinar cells, whereas no significant binding was observed on any part of the apical surfaces of these cells. Labeling density of gold particles was highest on the basolateral surface of the interlobular duct cells, secondarily highest on the basolateral surface of the intralobular duct cells, and lowest on the basolateral surface of the acinar cells. The distribution pattern of Na+, K(+)-ATPase in the acinar cells and the duct cells suggest that this enzyme may play an important role in primary secretion and in determining the composition of electrolytes in the final secretion, respectively. PMID- 1309730 TI - Redistribution and reduction of interphotoreceptor retinoid-binding protein during ocular coronavirus infection. AB - Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravitreal inoculation) was examined on interphotoreceptor retinoid-binding protein (IRBP), the glycolipoprotein in the interphotoreceptor matrix (IPM) thought to transport retinoids between the photoreceptors and the RPE. Changes in IRBP distribution accompanied virus-associated retinal pathology, including photoreceptor loss and RPE abnormalities. Immunohistochemistry on days 3 and 6 showed that IRBP had diffused into the neural retina away from the IPM. The IRBP became localized abnormally in the same areas as virus-induced lesions, shown by staining adjacent sections with a monoclonal antibody specific for the viral nucleocapsid protein. Moreover, the level of IRBP in isolated retinas, measured in an immunoslot-blot assay, decreased significantly by day 3 and remained low through day 23. This decrease was confirmed in eyecups isolated on day 6. It may be caused in part by loss of photoreceptors and diffusion of IRBP through the retina into the vitreous. These studies show that a virus may induce an acute, limited infection in the retina that can be cleared by the host. However, the infection initiated a series of events resulting in long-term reduction and redistribution of a critical photoreceptor protein. PMID- 1309731 TI - Immunohistopathologic findings in herpes simplex virus chorioretinitis in the von Szily model. AB - After anterior chamber inoculation of herpes simplex virus type 1 (HSV-1), some mice have a characteristic pattern of ocular disease, including ipsilateral anterior uveitis, relative sparing of the ipsilateral retina, and necrotizing contralateral chorioretinitis. It was reported previously that susceptibility to the contralateral chorioretinitis is associated with the Igh-1 locus; congenic mice differing at this locus have different rates of contralateral disease. The immunohistopathologic findings of this model in Igh-1 disparate congenic mice are reported after examining immune cell populations (CD4, CD8, Thy 1.2, Ia, Mac, and immunoglobulin G cells) in both ipsilateral and contralateral eyes and the recruitment kinetics of these cell types in various ocular tissues. In both HSV susceptible BALB/c and HSV-resistant C.B-17 mice, the ipsilateral eye undergoes early cellular infiltration, and the contralateral retina is devoid of cells until day 10 postinoculation. In BALB/c mice, a late dramatic rise develops in Mac and Ia cells in the ipsilateral and contralateral choroid (P less than 0.005) compared with C.B-17 mice. The C.B-17 mice have an earlier, mild cellular infiltration of the uveal tract in the ipsilateral eye, abrogation of the late Mac and Ia cellular recruitment in the ipsilateral choroid, and an absent contralateral response. These strain-specific immunohistopathologic differences help to explain Igh-1-linked HSV retinitis patterns in this model. PMID- 1309733 TI - Identification of mitochondrial proteins in membrane preparations from Chlamydomonas reinhardtii. AB - Preparations enriched in Chlamydomonas reinhardtii thylakoids have proven useful in the study of photosynthesis. Many of their polypeptides however remain unidentified. We report here on three of those, h1 (34 kDa), h2 (11 kDa), and P3 (63 kDa). h1, h2, and P3 are present in all tested mutants of C. reinhardtii lacking either one or several of the photosynthetic chain complexes or depleted in thylakoid membranes. h2 is an ascorbate-reducible, soluble c550-type cytochrome encoded in the nucleus. It cross-reacts immunologically with mitochondrial cytochromes c from various sources and contains a hexapeptide encoded in C. reinhardtii cytochrome c cDNA. P3, a nuclear-encoded peripheral protein, cross-reacts with various ATP synthase beta subunits. Its N-terminal sequence is encoded in C. reinhardtii mitochondrial beta subunit cDNA. h1 behaves as an integral hemoprotein; it is absent in a mitochondrial mutant that carries a deletion in apocytochrome b gene. We conclude that C. reinhardtii mitochondrial membranes copurify with thylakoid membranes. h1 is part of the cytochrome bc1 complex, h2 is cytochrome c, and P3 is the beta subunit of mitochondrial ATP synthase. PMID- 1309732 TI - Quantitative and qualitative differences in guanine nucleotide binding protein activation by formyl peptide and leukotriene B4 receptors. AB - Formyl peptides and leukotriene B4 (LTB4) stimulate disparate neutrophil functional responses and second messenger generation. The hypothesis that differences in receptor-guanine nucleotide-binding proteins (G protein) interaction account for the disparate responses was examined using HL-60 granulocyte plasma membranes. The quantity of receptor-coupled G proteins was determined by guanosine 5'-(gamma-thio)triphosphate (GTP gamma S) equilibrium binding in the presence or absence of f-Met-Leu-Phe and/or LTB4. About one-third of the total GTP gamma S binding sites were coupled to f-Met-Leu-Phe receptors, to LTB4 receptors, and to receptors when both ligands were added simultaneously. The dissociation constant of GTP gamma S-binding sites in the presence of LTB4 was significantly greater than that in the presence of f-Met-Leu-Phe. f-Met-Leu Phe shifted the GDP dose-inhibition curve for GTP gamma S binding further to the right than did LTB4. The apparent initial rate of GTP hydrolysis and GTP gamma S binding stimulated by f-Met-Leu-Phe was significantly greater than that stimulated by LTB4. There were significantly more formyl peptide receptors than LTB4 receptors, however, formyl peptide and LTB4 receptor density did not differ under GTP gamma S binding assay conditions. The rate of GTP hydrolysis stimulated by LTB4 was not increased in membranes containing twice the LTB4 receptor density. We conclude that formyl peptide receptors stimulate more rapid activation of a common pool of G proteins than LTB4 receptors because of a significantly reduced affinity of formyl peptide receptor-activated G proteins for GDP. PMID- 1309734 TI - Studies on the assembly and stability of the metal-thiolate clusters of metallothionein in dimethyl sulfoxide. AB - Solvent perturbation studies in 100% dimethyl sulfoxide (Me2SO) have been carried out on rabbit liver metallothionein (MT) in an effort to learn more about the factors stabilizing the three-dimensional structure and the mechanism of cluster formation. As indicated by the electronic absorption spectra of Co7 metallothionein, the reconstituted protein preserves its structural integrity in this solvent. Minor spectral differences between water and Me2SO were fully reversible. The titration of apoMT with cobalt(II) in Me2SO, followed by UV visible-near-infrared electronic absorption, circular dichroism, magnetic circular dichroism, and EPR spectroscopy, indicate that the protein can refold in this solvent. A comparison with the previous titration data in water reveals that the first four titration steps in both solvents are identical, indicating a thermodynamically controlled folding process. However, the reversed order of the cluster completion between Me2SO and water may suggest the involvement of a kinetically controlled folding process in the last three titration steps. A new cluster form developed with approximately nine Co(II) equivalents. PMID- 1309735 TI - Purified I kappa B-beta is inactivated upon dephosphorylation. AB - In uninduced cells, the NF-kappa B transcription factor resides in the cytoplasm in complex with an inhibitory protein, I kappa B. I kappa B is a specific inhibitor of DNA binding and apparently prevents nuclear uptake of NF-kappa B. Stimulation of cells, for instance with the cytokine tumor necrosis factor, releases I kappa B and allows nuclear translocation and DNA binding of NF-kappa B to regulatory DNA sequences in many genes. We recently reported on the purification of a major form of I kappa B, referred to as I kappa B-alpha, with a molecular size of 37 kDa. Here, we purified and characterized I kappa B-beta, a chromatographically distinct second form of I kappa B. I kappa B-beta has a size of 43 kDa and, as I kappa B-alpha, an acidic isoelectric point between 4.8 and 5.0. Both forms of I kappa B were inactivated by a treatment with protein kinases A and C in vitro. In contrast to I kappa B-alpha, I kappa B-beta lost its inhibiting activity upon a treatment with phosphatase. Phosphatase treatment also released active NF-kappa B from its inactive complex with I kappa B-beta suggesting that the activation of NF-kappa B in intact cells might not only rely on phosphate transfer onto I kappa B but also on phosphate removal from one form of I kappa B. PMID- 1309736 TI - Ligation of the diiron site of the hydroxylase component of methane monooxygenase. An electron nuclear double resonance study. AB - Electron nuclear double resonance (ENDOR) spectroscopy is used to probe the coordination of the mixed valence (Fe(II).Fe(III)) diiron cluster of the methane monooxygenase hydroxylase component (MMOH-) isolated from Methylosinus trichosporium OB3b. ENDOR resonances are observed along the principal axis directions g1 = 1.94 and g3 = 1.76 from at least nine different protons and two different nitrogens. The nitrogens are strongly coupled and appear to be directly coordinated to the cluster irons. The ratio of their superhyperfine coupling constants is roughly 4:7, which equals the ratio of the spin expectation values of the Fe(II) and Fe(III) in the ground state and suggests that at least one nitrogen is coordinated to each iron of the mixed valence cluster. Moreover, the superhyperfine and quadrupole coupling constants assigned to the Fe(III) site (AN = 13.6 MHz, PN = 0.7 MHz) are comparable with those observed for semimethemerythrin sulfide (AN = 12.1 MHz, PN = 0.7 MHz), for which the nitrogen ligands are histidines. At least three of the coupled protons exchange slowly when MMOH- is incubated in D2O, and 2H ENDOR resonances are subsequently observed. These observations are also consistent with histidine ligation of the iron cluster. On addition of the inhibitor dimethyl sulfoxide (Me2SO) to MMOH- the EPR spectrum sharpens and shifts dramatically. Only one set of 14N ENDOR resonances is observed with frequencies equal to those assigned to the Fe(III) histidine resonances of uncomplexed MMOH- suggesting that the nitrogen coordination to the Fe(II) site is altered or possibly lost in the presence of Me2SO. 2H ENDOR resonances are observed in the presence of d6-Me2SO indicating that the inhibitor Me2SO binds near or possibly to the diiron cluster. In contrast, no 2H ENDOR resonances are observed from d4-methanol upon addition to MMOH-. Thus, the changes observed in the EPR spectrum of MMOH- upon addition of methanol may result from binding to a site away from the diiron cluster or from bulk solvent effects on the protein structure. PMID- 1309737 TI - Characterization of a novel g' = 2.95 EPR signal from the binuclear center of mitochondrial cytochrome c oxidase. AB - The oxidized binuclear heme a3/CuB center of slow forms of bovine cytochrome oxidase exhibits a characteristic EPR signal at g' = 12. Following the (rapid) dithionite reduction of heme a and CuA, an additional EPR signal becomes apparent at g' = 2.95. As electrons enter the binuclear center this signal decays at the same slow rate as the g' = 12 signal. In the fully oxidized slow enzyme the small g' = 2.95 signal is usually masked by the g = 3 heme a signal, but it is readily detectable at low temperatures and high microwave powers. It is present in both the intrinsic and formate-ligated slow enzymes, but not in any form of fast preparation. The g' = 2.95 signal has similar temperature dependence and microwave power saturation characteristics to the g' = 12 signal. We conclude that the signal arises from the same population of binuclear centers responsible for the g' = 12 signal. The appearance of a signal at g' = 2.95 in X-band EPR is consistent with, but does not prove, the model of Hagen where the g' = 12 signal arises from a ferryl heme a3, with CuB cuprous and EPR-silent (Hagen, W. R. (1982) Biochim. Biophys. Acta 708, 82-98). PMID- 1309738 TI - Cytochrome c binding affects the conformation of cytochrome a in cytochrome c oxidase. AB - Second derivative absorption spectroscopy has been used to assess the effects of complex formation between cytochrome c and cytochrome c oxidase on the conformation of the cytochrome a cofactor. When ferrocytochrome c is complexed to the cyanide-inhibited reduced or mixed valence enzyme, the conformation of ferrocytochrome a is affected. The second derivative spectrum of these enzyme forms displays two electronic transitions at 443 and 451 nm before complex formation, but only the 443-nm transition after cytochrome c is bound. This effect is not induced by poly-L-lysine, a homopolypeptide which is known to bind to the cytochrome c binding domain of cytochrome c oxidase. The effect is limited to cyanide-inhibited forms of the enzyme; no effect was observed for the fully reduced unliganded or fully reduced carbon monoxide-inhibited enzyme. The spectral signatures of these changes and the fact that they are exclusively associated with the cyanide-inhibited enzyme are both reminiscent of the effects of low pH on the conformation of cytochrome a (Ishibe, N., Lynch, S., and Copeland, R. A. (1991) J. Biol. Chem. 266, 23916-23920). These results are discussed in terms of possible mechanisms of communication between the cytochrome c binding site, cytochrome a, and the oxygen binding site within the cytochrome c oxidase molecule. PMID- 1309739 TI - Receptor-mediated internalization of bradykinin. DDT1 MF-2 smooth muscle cells process internalized bradykinin via multiple degradative pathways. AB - This study was undertaken to evaluate the role of internalization in the action of the peptide autacoid bradykinin (BK). At 4 degrees C [3H]BK binds to an apparently single class of B2 kinin receptors on DDT1 MF-2 smooth muscle cells (C. M. Munoz, S. Cotecchia, and L. M. F. Leeb-Lundberg, manuscript submitted). At this temperature the [3H]BK binding was confined exclusively to the cell surface. On the other hand, at 37 degrees C the B2 receptor-specific cell surface [3H]BK binding was rapidly followed by a receptor-specific internalization of [3H]BK (t1/2 approximately 9 min). The internalization reached a steady-state level after 30-40 min that was 80-100% of the level of specifically bound [3H]BK on the cell surface at 4 degrees C, and this level was maintained for greater than or equal to 2 h. Internalized [3H]BK was routed via at least two intracellular degradative pathways which were distinguished primarily based on subcellular localization but also on a small but significant difference in the rate of [3H]BK degradation. One pathway was localized in a plasma membrane-enriched fraction and had a relatively high degradative capacity. Another pathway was localized in a microsomal fraction and had a relatively low degradative capacity. The internalized [3H]BK activity was rapidly released into the media (t1/2 approximately 24 min). Following a single round of internalization, the released activity consisted almost exclusively of small [3H]BK fragments (less than [3H]BK(1-5)). In contrast, at steady-state [3H]BK represented 30-40% of the released activity. While chloroquine (100 microM) did not alter the rate of [3H]BK internalization or release or the intracellular distribution of [3H]BK, this agent significantly decreased the rate of [3H]BK degradation in both pathways. In all, these results show that B2 kinin receptor-mediated internalization of BK is a process integral to the interaction of BK with DDT1 MF 2 smooth muscle cells and may be a mechanism for terminating BK actions by rapidly removing extracellular free and receptor-bound BK and accessing various intracellular BK degradative pathways. PMID- 1309740 TI - Recombinant Gq alpha. Mutational activation and coupling to receptors and phospholipase C. AB - Gq mediates hormonal stimulation of phosphoinositide-specific phospholipase C (PI PLC). We mutated the alpha subunit of Gq (alpha q) to replace arginine 183 with cysteine. Mutations that substitute cysteine for the corresponding arginine residues of alpha s and alpha i2 constitutively activate their respective effector pathways, creating the gsp and gip2 oncogenes. Transient expression of alpha q-R183C in COS-7 and HEK-293 cells constitutively activates PI-PLC, but wild type (WT) alpha q does not. This suggests that the mutated arginines in alpha s, alpha i2, and alpha q share a common function in regulating the active state of these proteins and that the alpha q gene may serve as a target for oncogenic mutations in human tumors. In an attempt to develop an assay for receptor stimulation of recombinant alpha q, we co-expressed receptors with alpha q-WT. We found that the alpha 2-adrenoceptor stimulates PI-PLC activation in HEK 293 cells in a fashion that depends completely on co-expression of alpha q-WT. These findings create an experimental model, similar to that provided for alpha s by S49 cyc- cells, that should make it possible to analyze receptor and effector coupling by mutant alpha q against a null background. PMID- 1309741 TI - Activation of NADPH oxidase in human neutrophils permeabilized with Staphylococcus aureus alpha-toxin. A lower Km when the enzyme is activated in situ. AB - The NADPH oxidase is a multicomponent enzyme system that produces the reduced oxygen species essential for bacterial killing by polymorphonuclear leukocytes (PMN). Study of the oxidase has typically been carried out in cell-free systems in which Km values of 20-150 microM NADPH have been reported. However, when compared with affinities reported for other flavoprotein dehydrogenases and when considering the cellular concentration of NADPH/NADP+ of approximately 35 microM, the reported affinity of the oxidase for NADPH appears low. To investigate this apparent discrepancy we have studied the kinetics of NADPH oxidase activation in situ in human PMN permeabilized with Staphylococcus aureus alpha-toxin. alpha Toxin permeabilization of human PMN did not initiate NADPH oxidase activation at physiologic concentrations of NADPH. If permeabilized cells were stimulated with 1 microM formyl-methionyl-leucyl-phenylalanine, 10 microM guanosine 5'-O-(3 thiotriphosphate), 0.5 mM Ca2+, 5 micrograms/ml cytochalasin B in the presence of varying concentrations of NADPH, we were able to demonstrate activation of the oxidase complex as shown by superoxide dismutase-inhibitable reduction of cytochrome c. In this system we determined that the Km for oxidase activation was 4-7 microM NADPH, a 4-10-fold decrease from reported values. The oxidase was the enzyme being studied as shown by the absence of enzymatic activity in patients with chronic granulomatous disease. In addition, if the enzyme was initially activated in permeabilized cells, the cells homogenized, and the Km for the oxidase determined in a cell-free system, the observed Km reverted to previously reported values (36 microM). These results indicate that NADPH oxidase, studied in situ, has a significantly higher substrate affinity than that observed in isolated membranes and, moreover, indicate that substrate affinity is optimal for catalysis at reported concentrations of cytosolic NADPH. PMID- 1309742 TI - Regulation of formyl peptide receptor expression and its mRNA levels during differentiation of HL-60 cells. AB - When incubated with N6-2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP), HL-60 cells expressed formyl peptide receptor (FPR) (as assessed by ligand binding) and FPR transcripts in a time- and concentration-dependent fashion. Experiments using dbcAMP analogs modified at either the C-6 or C-8 position indicated that the process was mediated by a protein kinase A type I, and protein kinase A type I activity was isolated from undifferentiated HL-60 cells by DEAE-Sephacel chromatography. Forskolin mimicked the effects of dbcAMP. Forskolin and dbcAMP-dependent expression of FPR and FPR transcript was inhibited by staurosporine. Retinoic acid (but not retinal or retinol) was capable of inhibiting dbcAMP-dependent expression of FPR mRNA half-life. Dexamethasone enhanced the effects of dbcAMP and blocked the inhibitory effect of retinoic acid on expression of FPR and FPR transcripts. Phorbol 12-myristate 13-acetate (PMA) alone (1.5-15 nM) failed to induce HL-60 to express FPR and FPR transcripts. Low concentrations (1.5 nM) of PMA enhanced the ability of dbcAMP to induce HL-60 cells to express FPR and FPR transcript, whereas high (15 nM) concentrations of PMA inhibited dbcAMP effects. These results indicate that expression of FPR and FPR transcripts by HL-60 cells can be up- and down-regulated by agents that induce HL-60 cells to differentiate and that a "cross-talk" effect exists between protein kinase A and protein kinase C that modulates FPR gene transcription (and receptor expression) by these cells. PMID- 1309743 TI - The DNA helicase and adenosine triphosphatase activities of yeast Rad3 protein are inhibited by DNA damage. A potential mechanism for damage-specific recognition. AB - Purified Rad3 protein from the yeast Saccharomyces cerevisiae is a single stranded DNA-dependent ATPase and also acts as a DNA helicase on partially duplex DNA. In this study we show that the DNA helicase activity is inhibited when a partially duplex circular DNA substrate is exposed to ultraviolet (UV) radiation. Inhibition of DNA helicase activity is sensitive to the particular strand of the duplex region which carries the damage. Inhibition is retained if the single stranded circle is irradiated prior to annealing to an unirradiated oligonucleotide, but not if a UV-irradiated oligonucleotide is annealed to unirradiated circular single-stranded DNA. UV irradiation of single-stranded DNA or deoxyribonucleotide homopolymers also inhibits the ability of these polynucleotides to support the hydrolysis of ATP by Rad3 protein. UV radiation damage apparently blocks translocation of Rad3 protein and results in the formation of stable Rad3 protein-UV-irradiated DNA complexes. As a consequence, Rad3 protein remains sequestered on DNA, presumably at sites of base damage. The sensitivity of Rad3 protein to the presence of DNA damage on the strand along which it translocates provides a potential mechanism for damage recognition during nucleotide excision repair and may explain the absolute requirement for Rad3 protein for damage-specific incision of DNA in yeast. PMID- 1309744 TI - Chromostatin receptors control calcium channel activity in adrenal chromaffin cells. AB - One of the functions of chromogranin A (CGA), the major soluble component of secretory granules in both adrenal medullary chromaffin cells and many other endocrine cell types appears to be that of a prohormone. CGA is the precursor of several peptides including pancreastatin, a 49-residue peptide, and a 20-residue peptide, chromostatin, which have been identified as biologically active peptides. Chromostatin produces a dose-dependent inhibition (ID50 of 5 nM) of the secretagogue-evoked catecholamine secretion from chromaffin cells. Here we report that chromostatin potently inhibits L-type calcium currents recorded with the nystatin-perforated patch technique in cultured chromaffin cells. This inhibitory effect of chromostatin on calcium currents was not observed in experiments using the classical patch-clamp whole-cell approach which induces the leakage of cytoplasmic components. Using 125I-chromostatin, we show that chromostatin exhibits a fully reversible and saturable binding to the plasma membrane of cultured chromaffin cells. Analysis of binding experiments at equilibrium indicates the existence of one class of binding sites with a Bmax of 2.7 pmol/mg of chromaffin cell proteins and an apparent Kd of 6.5 nM. This high affinity is in good correlation with the half-maximal concentration (ID50 5 nM) of chromostatin inhibiting catecholamine secretion from chromaffin cells. Specificity of the chromostatin binding was further assessed by displacement experiments with unlabeled CGA-related or -unrelated peptides. We found an excellent quantitative correlation between the affinities of the various peptides determined by binding assays and their functional potency tested on catecholamine secretion: bovine chromostatin greater than human chromostatin greater than CGA much greater than rat chromostatin, pancreastatin, CAP-14, substance P, and Leu enkephalin. Cross-linking experiments reveal that chromostatin associates specifically with an 80-kDa plasma membrane protein. These results together with the patch-clamp experiments support the idea that chromaffin cells possess specific chromostatin receptors and that activation of such receptors leads to the inhibition of L-type voltage-sensitive calcium channels through an intracellular second messenger pathway. PMID- 1309745 TI - In vitro translocation of secretory proteins possessing no charges at the mature domain takes place efficiently in a protonmotive force-dependent manner. AB - The effect of charges existing on the mature domain of secretory proteins on the efficiency and protonmotive force dependence of translocation into everted membrane vesicles of Escherichia coli was studied. Model secretory proteins devoid of charges on the mature domain were constructed at the DNA level using proOmpF-Lpp as the starting protein. The chargeless presecretory proteins thus constructed were translocated and processed for the signal peptide much faster than proOmpF-Lpp and the rate of translocation was appreciably enhanced by imposition of the protonmotive force. Not only the membrane potential but also delta pH were effective in stimulating the rate of translocation of the chargeless proteins. The results indicate that the mature domain does not have to be charged for the secretory translocation and that the major requirement of the protonmotive force for the secretory translocation is not for the movement, including an electrophoretic one, of charged regions of the mature domain. All of the proOmpF-Lpp derivatives thus constructed were translocated efficiently into everted membrane vesicles in a SecA-dependent manner, irrespective of their size. The mature domain of the smallest one was 45 amino acid residues in length. Contrary to the views previously presented by other workers, these results suggest that there is no sharp boundary at the reported regions for the translocation of presecretory proteins across the cytoplasmic membrane or for the requirement of SecA. PMID- 1309746 TI - In vitro association of phosphatidylinositol 3-kinase activity with the activated insulin receptor tyrosine kinase. AB - We previously have shown that insulin treatment of cells greatly increases the activity of phosphatidylinositol (PI) 3-kinase in immunoprecipitates made with an antibody to phosphotyrosine. However, the association of PI 3-kinase activity with the activated insulin receptor is not significant under these conditions. In the present study, we have attempted to reconstitute the association of PI 3 kinase activity with the activated insulin receptor in vitro. PI 3-kinase activity does indeed associate with the autophosphorylated insulin receptor in our in vitro system. The autophosphorylation of the insulin receptor and/or its associated conformational change appear to be necessary for the association of PI 3-kinase activity with the receptor, since kinase negative receptor failed to bind PI 3-kinase activity. After binding, PI 3-kinase or its associated protein seems to be released from the activated receptor after the completion of its tyrosine phosphorylation by the receptor. Tyr960 in the juxtamembrane region of the insulin receptor beta-subunit seems to be involved in the association of PI 3 kinase activity with the receptor, but not C terminus region of the beta-subunit including two tyrosine autophosphorylation sites (Tyr1316 and Tyr1322). The in vitro assay system for the association of PI 3-kinase activity with the insulin receptor can be utilized to study the mechanism of interaction of these molecules and will be an useful method to detect other associated molecules with the insulin receptor. PMID- 1309747 TI - Topoisomerase II plays an essential role as a swivelase in the late stage of SV40 chromosome replication in vitro. AB - The effects of topoisomerases I and II on the replication of SV40 DNA were examined using an in vitro replication system of purified proteins that constitutes the monopolymerase system. In the presence of the two topoisomerases, two distinct nascent DNAs were formed. One product arising from the replication of the leading template strand was approximately half the size of the template DNA, whereas the other product derived from the lagging template strand consisted of short DNAs. These products were synthesized from both SV40 naked DNA and SV40 chromosomes. For the replication of SV40 naked DNA, either topoisomerase I or II maintained replication fork movement and supported complete leading strand synthesis. When SV40 chromosomes were replicated with the same proteins, reactions containing only topoisomerase I produced shorter leading strands. However, mature size DNA products accumulated in reactions supplemented with topoisomerase II, as well as in reactions containing only topoisomerase II. In the presence of crude extracts of HeLa cells, VP-16, a specific inhibitor of topoisomerase II, blocked elongation of the nascent DNA during the replication of SV40 chromosomes. These results indicate that topoisomerase II plays a crucial role as a swivelase in the late stage of SV40 chromosome replication in vitro. PMID- 1309748 TI - ADP-ribosylation of gelsolin-actin complexes by clostridial toxins. AB - ADP-ribosylation of the 1:1 (G-A) and 1:2 (G-A-A) gelsolin-actin complexes by Clostridium perfringens iota toxin and Clostridium botulinum C2 toxin was studied. Iota toxin ADP-ribosylated actin in the G-A complex from human platelets as effectively as skeletal muscle actin. The Km for NAD (4 microM) was identical for both substrates. C2 toxin ADP-ribosylated actin in the G-A complex with lower efficacy than nonmuscle actin from platelet cytosol. In the G-A-A complex both actin molecules were ADP-ribosylated by iota toxin. The G-A complex bound ADP ribosylated actin (Ar) to form the G-A-Ar complex in which the weakly bound actin is ADP-ribosylated. Vice versa, ADP-ribosylated 1:1 gelsolin-actin complex (G-Ar) was able to bind unmodified actin to yield the G-Ar-A complex. ADP-ribosylation did not change the nucleation activity of either the G-Ar complex or the G-Ar-A complex. When monomeric actin was added to the G-A-Ar complex, polymerization of actin was delayed by about 10 min. According to a quantitative kinetic analysis, the delay of polymerization corresponded to the rate of dissociation of ADP ribosylated actin from the G-A-Ar complex. This suggests that the nucleation activity of the G-A-A complex is inhibited by ADP-ribosylation of the weakly bound actin and that the inhibition can be removed by dissociation of ADP ribosylated actin from the G-A-Ar complex. PMID- 1309749 TI - Immunochemical characterization of the non-NMDA glutamate receptor using subunit specific antibodies. Evidence for a hetero-oligomeric structure in rat brain. AB - Antibodies were made to synthetic peptides corresponding to sequences specific to the glutamate receptor (GluR) subunits, GluR1-4. The specificity of the antibodies was established by Western blotting using membranes of simian kidney cells (COS-7) transfected with GluR subunit DNA. Four antibodies were found to be selective for each of the four GluR subunits, and a fifth antibody recognized both GluR2 and 3. All five antibodies immunoadsorbed Triton X-100-solubilized rat brain [3H]AMPA binding activity and labeled an Mr = 108,000 band in samples of rat brain. The structure of the Triton X-100-solubilized GluR was studied using subunit-specific antibodies covalently attached to protein A-agarose and analyzing GluR subunits bound to the antibodies by Western blotting. Each of the four subunit-specific antibodies immunoadsorbed its respective GluR subunit as well as the other three forms of GluR, showing that the detergent solubilized GluR exists as hetero-oligomers composed of two or more of the four subunits. Evidence supporting a similar structure for membrane bound GluR was obtained using synaptic membranes chemically cross-linked with dithiobis(succinimidylpropionate). GluR was immunoaffinity-purified using the GluR2 and 3-selective antibody. This antibody, covalently attached to protein A agarose, adsorbed 55% of [3H]AMPA binding activity, and after elution with 1 M KSCN, 22-37% of the binding activity was recovered. Analysis of the purified product showed a major immunoreactive band at Mr = 108,000, and silver staining identified the same major band and no additional polypeptides. The GluR receptor complex, therefore, appears to be made up exclusively of GluR1-4. In the purified GluR preparation, in addition to the Mr = 108,000 band, three higher molecular weight immunoreactive components were also detected. These bands migrated at Mr = 325,000, 470,000, and 590,000. Similar sized proteins were seen in the cross linked synaptic membrane sample, with the Mr = 590,000 component being substantially enriched after cross-linking. The Mr = 590,000 band is the largest component detected, and it has a size consistent with its being a pentamer of the Mr = 108,000 protein. PMID- 1309750 TI - A regulatory cis element and a specific binding factor involved in the mitogenic control of murine ribosomal protein L32 translation. AB - The mRNA encoding ribosomal protein L32 redistributes from untranslated subribosomal particles into polysomes after mitogenic activation of quiescent T lymphocytes and fibroblasts. To identify the regions of the L32 mRNA which are important in regulating its cytoplasmic location we constructed a plasmid containing the murine L32 cDNA under the control of the Rous sarcoma virus (RSV) long terminal repeat promoter and introduced this construct into murine 3T3 fibroblasts. The mRNA transcribed from the RSV-L32 construct redistributed from subribosomal particles into polysomes in response to mitogenic activation in a manner similar to endogenous L32 mRNA. A conserved polypyrimidine region present at the 5' terminus of all ribosomal protein mRNAs is required for translational regulation of L32 mRNA since deletion of this sequence resulted in a mRNA that was not sequestered in subribosomal particles in quiescent cells. A radioactive RNA probe containing the first 34 nucleotides of the L32 5'-untranslated region, including the polypyrimidine region, specifically interacted with a protein of about 56 kDa. This protein did not bind detectably to RNA probes lacking the polypyrimidine sequence. Binding activity was similar in protein extracts made from resting and activated cells, suggesting that binding of the 56-kDa protein as measured in this assay is not regulated. This protein is a member of what may be an emerging family of polyribopyrimidine-binding proteins with diverse biochemical functions. PMID- 1309751 TI - Interleukin 4 inhibition of prostaglandin E2 synthesis blocks interstitial collagenase and 92-kDa type IV collagenase/gelatinase production by human monocytes. AB - Activation of human monocytes results in the production of interstitial collagenase through a prostaglandin E2 (PGE2)-cAMP-dependent pathway. Inasmuch as interleukin 4 (IL-4) has been shown to inhibit PGE2 synthesis by monocytes, we examined the effect of IL-4 on the production of human monocyte interstitial collagenase. Additionally, we also assessed the effect of IL-4 on the production of 92-kDa type IV collagenase/gelatinase and tissue inhibitor of metalloproteinase-1 (TIMP-1) by monocytes. The inhibition of PGE2 synthesis by IL 4 resulted in decreased interstitial collagenase protein and activity that could be restored by exogenous PGE2 or dibutyryl cyclic AMP (Bt2cAMP). IL-4 also suppressed ConA-stimulated 92-kDa type IV collagenase/gelatinase protein and zymogram enzyme activity that could be reversed by exogenous PGE2 or Bt2cAMP. Moreover, indomethacin suppressed the ConA-induced production of 92-kDa type IV collagenase/gelatinase. These data demonstrate that, like monocyte interstitial collagenase, the conA-inducible monocyte 92-kDa type IV collagenase/gelatinase is regulated through a PGE2-mediated cAMP-dependent pathway. In contrast to ConA stimulation, unstimulated monocytes released low levels of 92-kDa type IV collagenase/gelatinase that were not affected by IL-4, PGE2, or Bt2cAMP, indicating that basal production of this enzyme is PGE2-cAMP independent. IL-4 inhibition of both collagenases was not a result of increased TIMP expression since Western analysis of 28.5-kDa TIMP-1 revealed that IL-4 did not alter the increased TIMP-1 protein in response to ConA. These data indicate that IL-4 may function in natural host regulation of connective tissue damage by monocytes. PMID- 1309752 TI - Genetic and biochemical characterization of the trpB8 mutation of Escherichia coli tryptophan synthase. An amino acid switch at the sharp turn of the trypsin sensitive "hinge" region diminishes substrate binding and alters solubility. AB - The trpB8 mutation of Escherichia coli tryptophan synthase is unique in that the cells bearing this lesion are not only capable of utilizing indole for growth, but they also accumulate indole, under conditions of tryptophan limitation. The lesion was shown by DNA sequencing to be a G to C transversion at nucleotide 5528 of the trp operon, resulting in a Gly to Arg switch at codon 281. Gly-281, within the trypsin-sensitive "hinge" region, is invariant among all known beta polypeptides. The catalytic activity of the mutant beta 2(B8) protein is dramatically stimulated by alpha subunit, both in vivo and in vitro. In the absence of alpha subunit, ammonium ion effectively stimulated the activity in an apparently cooperative manner. The pH optimum for the mutant subunit was 9.8, which is 2 units higher than that of wild type. In contrast to the wild-type subunit, beta(B8) partially aggregated within cells upon overexpression. At the optimal concentration of ammonium ions (2.25 M), the beta 2(B8) mutant enzyme displayed lower affinity than wild-type enzyme toward indole and L-serine, but the Vmax was almost unchanged. The physicochemical behavior of beta 2(B8) is supported by computer graphic modeling studies. An open versus closed model of conformational change within the beta 2 protein is proposed. A plausible role for the hinge region is discussed. PMID- 1309753 TI - Posttranscriptional regulation of the asialoglycoprotein receptor by cGMP. AB - The human asialoglycoprotein receptor expressed by the HepG2 cell line is composed of the two homologous polypeptides H1 and H2. Transblot analysis of HepG2 cell lysates indicated that the progressive loss in the steady-state level of asialoglycoprotein receptor (ASGR) when cells were maintained in medium supplemented with dialyzed fetal bovine serum was reversed by the addition of cell-permeant 8-bromo-cGMP. Estimates of the steady-state levels of H1- and H2 related mRNA by Northern blot analysis indicated that the reduction of ASGR was not the result of a concomitant reduction in gene transcript number. No difference in the translatability of the mRNAs derived from cells grown in medium supplemented with fetal bovine serum or its dialyzed counterpart was detected. Resolution of the mRNAs by sucrose gradient centrifugation suggests that cGMP mediated posttranscriptional regulation of ASGR expression was due to a shift of both H1 and H2 mRNAs from the ribonucleoprotein fraction into a translationally active membrane-associated polysomal pool. PMID- 1309754 TI - Membrane association of active 5-lipoxygenase in resting cells. Evidence for novel regulation of the enzyme in the rat alveolar macrophage. AB - The enzyme 5-lipoxygenase (5-LO) catalyzes the first two steps in the metabolism of arachidonic acid to leukotrienes, substances which play pivotal roles both in normal host defense and in pathologic states of inflammation. Recent studies in granulocytic cells have shown that activation of 5-LO involves its Ca(2+) dependent translocation from cytosol to membrane compartments. However, little information exists about the molecular regulation of 5-LO in macrophages, even though these cells comprise the resident effector cell population of most organs. We therefore examined the levels of 5-LO activity and immunoreactive protein in cytosol and membrane fractions of resident rat alveolar (AM) and peritoneal macrophages (PM) and compared them with the well studied human neutrophil (polymorphonuclear leukocyte). In the resting state, PM resembled polymorphonuclear leukocyte in that most of their cell-free 5-LO activity, as well as protein content, were localized to the cytosol fraction. By contrast, resting AM contained most of their activity and almost half of their immunoreactive protein in the crude membrane fraction. The inability of the drug MK-886 to reverse this membrane association suggested that the 5-LO-activating protein was not the site of binding in the resting cell; however, this drug completely inhibited leukotriene B4 synthesis in ionophore A23187-stimulated AM, indicating that an interaction between 5-LO and 5-LO-activating protein was nonetheless required for product synthesis upon stimulation. Translocation of cytosolic 5-LO protein could not be convincingly demonstrated in A23187 stimulated AM, suggesting that the pool of 5-LO enzyme responsible for product formation originated in the membrane rather than the cytosol fraction of the resting cell. The AM therefore represents the first mammalian cell in which 5-LO has been recovered from the membrane fraction (a) of a resting cell and (b) in active form. These novel findings extend our understanding of the molecular regulation of 5-LO and may be of importance in designing strategies to limit inflammation in the lung and other sites. PMID- 1309755 TI - Processing, intracellular transport, and functional expression of endogenous and exogenous alpha-beta 3 Na,K-ATPase complexes in Xenopus oocytes. AB - The minimal functional Na,K-ATPase unit is composed of a catalytic alpha-subunit and a glycosylated beta-subunit. So far three putative beta-isoforms have been described, but only beta 1-isoforms have been identified clearly as part of a purified active enzyme complex. In this study we provide evidence that a putative beta 3-isoform might be the functional component of Xenopus oocyte Na,K-ATPase. beta 3-isoforms are expressed in the oocyte plasma membrane together with alpha subunits, but beta 3-isoforms are synthesized to a lesser extent than alpha subunits. The unassembled oocyte alpha-subunits accumulate in an immature trypsin sensitive form most likely in the endoplasmic reticulum (ER). Injection of both beta 1- and beta 3-cRNA into oocytes abolishes the transport constraint of the oocyte alpha-subunit, renders it trypsin-resistant, and finally leads to an increased number of functional pumps at the plasma membrane. In addition, beta 3 isoforms as beta 1-isoforms depend on the concomitant synthesis of alpha-subunits to be able to leave the ER and to become fully glycosylated. Finally, alpha-beta 1 and alpha-beta 3 complexes expressed at the plasma membrane appear to have similar transport properties as assessed by ouabain binding, rubidium uptake, and electrophysiological measurements in oocytes coexpressing exogenous alpha 1- and beta 1- or beta 3-isoforms. Thus our data indicate that beta 3-isoforms have functional qualities similar to beta 1-isoforms. They can assemble and impose a structural reorganization to newly synthesized alpha-subunits which permits the exit from the ER and the expression of functional Na,K-pumps at the plasma membrane. PMID- 1309756 TI - The insertion of monoamine oxidase A into the outer membrane of rat liver mitochondria. AB - Human monoamine oxidase A that had been synthesized in a reticulocyte lysate translation system was capable of binding to and inserting into either rat liver mitochondria or isolated mitochondrial outer membranes. The inserted form was as resistant to proteinase K as endogenous mitochondrial monoamine oxidase A. The insertion, but not the binding, of monoamine oxidase A was prevented by depleting the reaction mixture of either ATP (with apyrase) or ubiquitin (with purified antibodies against this polypeptide). Addition of ATP or ubiquitin, respectively, to these depleted mixtures restored the insertion of the enzyme. In the absence of mitochondria, in vitro synthesized monoamine oxidase A did not catalyze its own alkylation by the mechanism-based inhibitor, [3H]clorgyline. However, both monoamine oxidase A that had been membrane-inserted in vitro and monoamine oxidase A that had been bound to the mitochondria under conditions of ATP depletion catalyzed adduct formation. Furthermore, reaction of either clorgyline or another mechanism-based inhibitor, pargyline, with the membrane-bound enzyme during ATP depletion inhibited the insertion of monoamine oxidase A when ATP was restored. These observations indicate that monoamine oxidase A acquired a catalytically active conformation on interaction with the mitochondrial outer membranes prior to its ATP and ubiquitin-dependent insertion into the membrane. PMID- 1309757 TI - Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature of electron-transfer proteins. Recommendations 1989. PMID- 1309758 TI - Direct evidence for cross-activation of cGMP-dependent protein kinase by cAMP in pig coronary arteries. AB - Elevation of either cAMP or cGMP causes smooth muscle relaxation. Whether these effects are mediated through cAMP-dependent protein kinase (cAK), cGMP-dependent protein kinase (cGK), or both is unknown. Pig coronary arteries were treated with sodium nitroprusside (SNP) or atrial natriuretic factor (ANF), relaxants which elevate cGMP, and with isoproterenol or forskolin, relaxants which elevate cAMP. Incubation of the arteries with 10 microM SNP produced a 3.3-fold increase in cGMP without altering cAMP; the cGK activity ratio (-cGMP/+cGMP) in these extracts was increased by 2.6-fold as determined by a newly developed assay, while the cAK activity ratio (-cAMP/+cAMP) was unchanged. The increase in cGK activity ratio by SNP was concentration-dependent and was nearly maximal at 30 s. Treatment of the tissue with 10 nM ANF also increased the cGK activity ratio (2.3 fold), but not that of cAK. 100 microM isoproterenol caused a 2.9-fold elevation of cAMP with no change in cGMP, but both cAK and cGK activity ratios were increased (2.3- and 1.6-fold, respectively). The increase in the cGK activity ratio could be mimicked by cAMP addition to control tissue extracts at the concentration measured in extracts of the isoproterenol-treated tissue. Forskolin (1 and 10 microM) also increased the cGK activity ratio (1.9- and 4.9-fold). The increases in cGK activity observed in extracts suggest that moderate elevation of either cGMP or cAMP causes intracellular cGK activation, thus producing relaxation of vascular smooth muscle. PMID- 1309759 TI - Ubiquitin conjugation to cytochromes c. Structure of the yeast iso-1 conjugate and possible recognition determinants. AB - Saccharomyces cerevisiae iso-1-cytochrome c was conjugated with ubiquitin (Ub) in vitro in a rabbit reticulocyte extract (Fraction II). By N-terminal protein sequencing, it was found for both the mono- and diubiquitinated products that the major Ub attachment site is on Lys4 (residue 9) of the cytochrome c. Thus, the residue ubiquitinated in iso-1-cytochrome c is identical with that previously determined for the yeast iso-2 form (Sokolik, C. W., and Cohen, R. E. (1991) J. Biol. Chem. 266, 9100-9107). For both cytochromes c, the proportions of diubiquitinated and higher order conjugates are drastically reduced when Ub is replaced with a Lys48----Arg variant, suggesting that the Ub-Ub moieties are linked predominantly through Lys48. Despite close similarities in structure and ubiquitination sites, conjugation to iso-2-cytochrome c is approximately 5-fold faster than for the iso-1 form; vertebrate cytochromes c are even poorer substrates, being ubiquitinated at only approximately 5% of the rate of the iso-2 protein. Comparison of several cytochrome c variants excludes alpha-N-acetylation or the identity of the N-terminal amino acid as the important recognition determinants in these reactions. The results, which include the finding that ferro and ferri-iso-2-cytochromes c are ubiquitinated equally, also are evidence against a simple correlation between ubiquitination efficiency and thermodynamic stability. Rather, the presence of a pair of lysines (Lys4-Lys5) within the relatively unstructured N-terminal extension of the yeast cytochromes c may be responsible for their preferential ubiquitination. PMID- 1309760 TI - Purification and molecular cloning of a butyrolactone autoregulator receptor from Streptomyces virginiae. AB - In streptomyces, low molecular weight compounds termed "autoregulators" have been isolated as primary signal molecules for triggering secondary metabolism and/or cytodifferentiation. Streptomyces virginiae produces a set of autoregulators termed virginiae butanolide A-E which trigger virginiamycin production, and possesses a high-affinity virginiae butanolide receptor (Kim, H.S., Nihira, T., Tada, H., Yanagimoto, M., and Yamada, Y. (1989) J. Antibiot. (Tokyo) 42, 769 778). The virginiae butanolide receptor has now been purified to apparent homogeneity with 14,000-fold purification and an 8.6% activity yield. The purified receptor showed a Mr of 36,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a maximum ligand binding of 33.0 nmol/mg protein, indicating a 1:1 binding stoichiometry (1.18 mol of virginiae butanolide/36 kDa of protein) between virginiae butanolides and the receptor. Due to a blockage at the amino terminus, fragment peptides were generated by lysyl endopeptidase and five partial amino acid sequences were determined. The gene (vbrA) encoding the virginiae butanolide receptor was identified on a 5.0-kbp BamHI fragment by hybridization to synthetic oligonucleotide probes, cloned, and sequenced. Nucleotide-sequence analysis predicted a 319-amino acid open reading frame (vbrA) in which all the partial amino acid sequences of the receptor appeared, and 166 bp downstream from it another open reading frame for a 144-amino acid protein which was designated as a ribosomal protein L11 from its high homology (62-64%) to the amino acid sequences of ribosomal protein L11 of several origins, and thus denoted as rplK. The C-terminal half of VbrA showed 36% overall homology to the amino acid sequence of an essential protein (NusG) of Escherichia coli. Furthermore, the gene assembly of vbrA-rplk of S. virginiae closely resembled that of nusG-rplK of E. coli, suggesting that vbrA may constitute a part of an essential gene cluster encoding components of transcriptional and translational apparatuses. PMID- 1309761 TI - A vasopressin analog that binds but does not activate V1 or V2 vasopressin receptors is not internalized into cells that express V1 or V2 receptors. AB - To assess whether receptor binding is sufficient to initiate vasopressin receptor endocytosis in cells expressing the vasopressin V1 or V2 receptors, we synthesized a novel fluorescent-labeled vasopressin analog, [1-(beta-mercapto beta, beta-cyclopentamethylene propionic acid), 2-(O-ethyl)-D-tyrosine, 4-valine, 8-lysine-N6-carboxytetramethylrhodamine] vasopressin (R-CLVP), that binds to vasopressin receptors but does not activate intracellular events such as the mobilization of intracellular calcium or the activation of adenylate cyclase. We compared the manner in which this analog was endocytosed in cells expressing V1 (A-10, rat smooth muscle cells) or V2 (LLC-PK1, porcine kidney cells) receptors with that of a full agonist, [1-(beta-mercaptopropionic acid), 8-lysine-N6 carboxytetramethylrhodamine] vasopressin (R-MLVP) [Lutz et al. (1990) J. Biol. Chem. 265, 4657-4663; Lutz et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87,6507 6511]. We showed that R-CLVP bound to both types of receptors with good affinity. It failed to increase cyclic AMP concentrations in LLC-PK1 cells and did not increase the mobilization of intracellular calcium in A-10 cells. It bound to the surface of both these cell types in a diffuse manner and it did not undergo receptor endocytosis in either cell type. In contrast, R-MLVP, an agonist that bound to both receptor subtypes and elicited changes in intracellular cyclic AMP and calcium, bound to the surface of these cells in a diffuse manner at early times after exposure, and rapidly underwent endocytosis. We conclude that binding of vasopressin to its receptors alone is insufficient to cause receptor endocytosis, and other events distal to the receptor are required to initiate endocytosis. R-CLVP should be a useful analog in determining the factors responsible for initiating receptor endocytosis. PMID- 1309762 TI - Mechanism of desensitization of the epidermal growth factor receptor protein tyrosine kinase. AB - The intrinsic protein-tyrosine kinase activity of the epidermal growth factor (EGF) receptor is required for signal transduction. Increased protein-tyrosine kinase activity is observed following the binding of EGF to the receptor. However, signaling is rapidly desensitized during EGF treatment. We report that EGF receptors isolated from desensitized cells exhibit a lower protein-tyrosine kinase activity than EGF receptors isolated from control cells. The mechanism of desensitization of kinase activity can be accounted for, in part, by the EGF stimulated phosphorylation of the receptor at Ser1046/7, a substrate for the multifunctional calmodulin-dependent protein kinase II in vitro. Mutation of Ser1046/7 by replacement with Ala residues blocks desensitization of the EGF receptor protein-tyrosine kinase activity. Furthermore, this mutation causes a marked inhibition of the EGF-stimulated endocytosis and down-regulation of cell surface receptors. Thus, the phosphorylation site Ser1046/7 is required for EGF receptor desensitization in EGF-treated cells. This regulatory phosphorylation site is located at the carboxyl terminus of the EGF receptor within the subdomain that binds src homology 2 regions of signaling molecules. PMID- 1309763 TI - Guanidinium derivatives act as high affinity antagonists of Na+ ions in occlusion sites of Na+,K(+)-ATPase. AB - We have screened various alkyl- and arylguanidinium derivatives as possible competitors of Na+ or Rb+ for the cation sites on renal Na+,K(+)-ATPase. Alkyl monoguanidinium or alkylbisguanidinium (BisG) compounds (chain lengths of C3 to C10) competitively inhibit the occlusion of Rb+ and Na+ with an order of affinities C10 greater than C8 greater than C6 greater than C4 greater than C3. BisG compounds are approximately twice as effective as the equivalent alkylmonoguanidinium compounds. In media of high ionic strength, affinities of tens of micromolar are observed, e.g. 26 microM for BisG 8. m-(mXBG)- and p xylylenebisguanidinium were synthesized and were found to compete with Rb+ or Na+ with intrinsic affinities of 7.7 and 8.2 microM, respectively. The hydrophobicity rather than the degree of proximity of the guanidinium groups in all BisG compounds appears to determine the binding affinity. A systematic search has been made of conditions in occlusion assays for which the inhibitor affinities are highest. When the pH is raised from 7.0 to 8.5, a 5-fold increase in affinity is observed, suggesting that the guanidinium derivatives compete with protons at sites of pKa approximately 7.5. Replacing Tris-HCl with choline chloride containing media raised apparent affinities approximately 2-fold. All guanidinium derivatives stabilize the E1 conformation of fluorescein-labeled Na+,K(+)-ATPase, acting as competitive Na+ analogues. In media containing only 1 mM Tris-HCl, pH 8.55, very high affinities were observed for binding to the fluorescein-labeled enzyme (e.g. 0.08 microM for mXBG). In very low ionic strength medium, the inhibition was still competitive with Rb+ ions. However, there was also evidence for nonspecific adsorption to the membranes. The following findings show that mXBG, a typical guanidinium derivative, behaves as a Na(+)-like antagonist. (a) It inhibits Na+,K(+)-ATPase activity, competing strongly with Na+ but only weakly with K+ ions. (b) It inhibits phosphorylation from ATP, competing with Na+ ions. (c) Like Na+ ions, it blocks phosphorylation from inorganic phosphate. Based on these results, we propose that the guanidinium group binds to a relatively wide vestibule at the cytoplasmic surface; but, unlike Na+ or K+ ions, it cannot pass into a narrower region of the cation transport path within the membrane. Therefore, it blocks the occlusion and active transport of cations. In the future, high affinity guanidinium derivatives may serve the purpose of locating cation-binding domains of the pump protein after being converted to reactive affinity or photoaffinity covalent labels. PMID- 1309765 TI - Purification and characterization of a brain-specific multifunctional calmodulin dependent protein kinase from rat cerebellum. AB - A brain-specific multifunctional calmodulin-dependent protein kinase, calmodulin dependent protein kinase IV, which exhibited characteristic properties quite different from those of calmodulin-dependent protein kinase II, was purified approximately 230-fold from rat cerebellum. The purified preparation gave two protein bands with molecular weights of 63,000 (alpha) and 66,000 (beta) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both of which showed protein kinase activity as examined by the activity gel method. The molecular weight of the enzyme was estimated as about 67,000 from sedimentation coefficient (3.2 S) and Stokes radius (50 A), indicating a monomeric structure of the enzyme. The enzyme phosphorylated smooth muscle myosin light chain, synapsin I, microtubule-associated protein 2, tau protein, myelin basic protein, histone H1, and tyrosine hydroxylase in a Ca2+/calmodulin dependent manner, suggesting that the enzyme is a multifunctional calmodulin-dependent protein kinase capable of phosphorylating a large number of substrates. A synthetic peptide, Lys-Ser-Asp Gly-Gly-Val-Lys-Lys-Arg-Lys-Ser-Ser-Ser-Ser, was found to be a specific substrate for this kinase and, using this peptide as substrate, the distribution of the enzyme activity in various rat tissues was examined. The activity was found in cerebral cortex, brain stem, and cerebellum, most abundantly in cerebellum, but other tissues tested, including liver, spleen, kidney, lung, heart, skeletal muscle, and adrenal gland showed very little activity. PMID- 1309764 TI - Extensive digestion of Na+,K(+)-ATPase by specific and nonspecific proteases with preservation of cation occlusion sites. AB - This paper extends our recent report that renal Na+,K(+)-ATPase is digested by trypsin in the absence of Ca2+ and presence of Rb+ ions to a stable 19-kDa fragment and smaller membrane-embedded fragments of the alpha chain and essentially intact beta chain. These are referred to as "19-kDa membranes." Occlusion of both Rb+ (K+) or Na+ ions is preserved, but ATP-dependent functions are lost (Karlish, S. J. D., Goldshleger, R., and Stein, W. D. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4566-4570). We now show that extensive digestion with nonselective fungal proteases (Pronase and proteinase K) alone, in combination, or after tryptic digestion can remove up to 70% of membrane protein without destroying Rb+ occlusion. In the most heavily digested membranes, the 19-kDa fragment or a slightly shorter 18.5-kDa fragment and smaller fragments of the alpha chain remain, whereas the beta chain is largely digested, leaving smaller membrane-embedded fragments (13-15 kDa). For either trypsin or Pronase digestion, preservation of Rb+ occlusion and the specific fragmentation pattern is observed only in the absence of divalent metal ions (Mg2+ or Ca2+) and presence of either Rb+ or Na+ or congener ions. Tryptic digestion at pH 7.0 can split the beta chain into two fragments of approximately 50 and 16 kDa joined by an S-S bridge. The 16 kDa fragment is protected against further digestion by the presence of Rb+ ions, but probably is not directly involved in occluding cations. Tryptic 19-kDa membranes show a clear and reproducible fragmentation pattern in which all predicted membrane segments are identifiable. Families of fragments from 19-kDa membranes, including seven peptides of 7.6-11.7 kDa, have been separated by size exclusion high performance liquid chromatography, concentrated, and resolved on 16.5% Tricine gels. N-terminal sequences of the different fragments have been determined after transfer to polyvinylidene difluoride paper. The most interesting findings are as follows. (a) Whereas the 19-kDa tryptic fragment begins at Asn831 as reported previously, the 18.5-kDa Pronase fragment begins at Thr834. (b) Fragments in tryptic 19-kDa membranes of 7.6-11.7 kDa begin at Asp68, Ile263, and Gln737, respectively. These include all putative transmembrane segments other than those in the 19-kDa fragment. (c) A Pronase fragment of 7.8 kDa begins at Thr834, i.e. apparently the 19-kDa fragment has been partially cut, without loss of Rb+ occlusion. (d) Tryptic 16- and approximately 50-kDa fragments of the beta chain begin at Ala5 and Gly143, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309766 TI - Cytosolic components involved in porcine neutrophil oxidase activation. Purification of a 47-kilodalton protein and reconstitution of the activation system. AB - Two cytosolic components, which cooperate with a 63-kDa cytosolic factor (Tanaka, T., Imajoh-Ohmi, S., Kanegasaki, S., Takagi, Y., Makino, R., and Ishimura, Y. (1990) J. Biol. Chem. 265, 18717-18720) in activation of the O(2-)-generating NADPH-oxidase in neutrophil membrane, were isolated and characterized from porcine neutrophils. One, which was purified to electrophoretic homogeneity, was a 47-kDa protein cross-reactive to an antibody raised against a portion of human 47-kDa cytosolic factor, a component of the human NADPH-oxidase activation system. Another one, designated here as the third component, was partially purified and found to contain 49- and 55-kDa proteins as the major constituents. No colored prosthetic group such as heme, flavin, and non-heme iron was detected in both cytosolic components. In a reconstituted assay system with a solubilized membrane preparation containing the dormant oxidase and with oleate as a stimulus, the 47-kDa protein together with the 63-kDa factor was essential for activating the dormant oxidase, while the third component was not essential for the activation of but enhanced the O(2-)-generation evoked by the former two components. Thus, the 47- and 63-kDa cytosolic proteins are the principal constituents of the activation system, while the other factors such as those contained in the third component may regulate the activity induced by the essential components. PMID- 1309767 TI - Metal ions cause the isomerization of certain intramolecular triplexes. AB - The influence of cations on the capacity of five oligopurine.oligopyrimidine mirror repeat sequences to adopt intramolecular triplexes (the usual H-y3 isomer and/or the rare H-y5 isomer) in recombinant plasmids was investigated. Unexpectedly, the presence of certain metal ions (magnesium, zinc, manganese, and calcium) stabilized the (GAA)4TTCGC(GAA)4 insert in the rare H-y5 when cloned into either of two different sequence backgrounds. Alternatively, either shortening or lengthening the sequence at the central interruption, which becomes the loop of the triplex, led to the formation of the canonical H-y3 under all conditions tested. Similarly, other oligopurine.oligopyrimidine mirror repeat sequences (i.e. (GAA)8 or (GGA)8) formed only the H-y3 under all experimental conditions. All triplexes were stabilized by negative supercoiling at pH 5.0; chemical probe and primer extension analyses served as critical structural tools. Hence, the nature of the central interruption sequence (the loop) of the mirror repeat is important for the stabilization of the H-y5. This region may be important for metal ion binding in the initial stages of triplex formation and thus may play a critical role in determining which isomer is formed. The possible biological role of a DNA sequence adopting three different conformations is discussed. PMID- 1309768 TI - Insulin stimulation of phosphatidylinositol 3-kinase activity maps to insulin receptor regions required for endogenous substrate phosphorylation. AB - We have studied the phosphatidylinositol 3-kinase (PtdIns 3-kinase) in insulin stimulated Chinese hamster ovary (CHO) cells expressing normal (CHO/IR) and mutant human insulin receptors. Insulin stimulation of CHO/IR cells results in an increase in PtdIns 3-kinase activity associated with anti-phosphotyrosine (alpha PY) immunoprecipitates, which has been previously shown to correlate with the in vivo production of PtdIns(3,4)P2, and PtdIns(3,4,5)P3 (Ruderman, N., Kapeller, R., White, M.F., and Cantley, L.C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1411 1415). Stimulation was maximal within 1 min and showed a dose response identical to that of insulin receptor autophosphorylation. The PtdIns 3-kinase also associated with the insulin receptor in an insulin-stimulated manner, as approximately 50% of the total alpha PY-precipitable activity could be specifically immunoprecipitated with anti-insulin receptor antibody. Mutant insulin receptors displayed variable ability to stimulate the PtdIns 3-kinase, but in all cases the presence of PtdIns 3-kinase in alpha PY immunoprecipitates correlated closely with the tyrosyl phosphorylation of the endogenous substrate pp185. In CHO cells expressing a kinase-deficient mutant (IRA1018), there was no observable insulin stimulation of PtdIns 3-kinase activity in alpha PY immunoprecipitates and no tyrosyl phosphorylation of pp185. Substitution of Tyr1146 in the insulin receptor regulatory region with phenylalanine partially impaired receptor autophosphorylation, pp185 phosphorylation, and insulin stimulated increases in alpha PY-precipitable PtdIns 3-kinase activity. In contrast, a deletion mutant lacking 12 amino acids from the juxtamembrane region (IR delta 960) displayed normal in vivo autophosphorylation but failed to stimulate the PtdIns 3-kinase or phosphorylate pp185. Finally, a mutant receptor from which the C-terminal 43 amino acids had been deleted (IR delta CT) exhibited normal insulin-stimulated autophosphorylation, pp185 phosphorylation, and stimulation of the PtdIns 3-kinase activity in alpha PY immunoprecipitates. These data suggest that the PtdIns 3-kinase is itself a substrate of the insulin receptor kinase or associates preferentially with a substrate. A comparison of the biological activities of the mutant receptors with their activation of the PtdIns 3-kinase furthermore suggests that the PtdIns 3-kinase may be linked to insulin's ability to regulate DNA synthesis and cell growth. PMID- 1309769 TI - Functional reconstitution of membrane proteins in monolayer liposomes from bipolar lipids of Sulfolobus acidocaldarius. AB - Membranes of Sulfolobus acidocaldarius, an extreme thermophilic archaebacterium, are composed of unusual bipolar lipids. They consist of macrocyclic tetraethers with two polar heads linked by two hydrophobic C40 phytanyl chains which are thought to be arranged as a monolayer in the cytoplasmic membrane. Fractionation of a total lipid-extract from S. acidocaldarius yielded a lipid fraction which forms closed and stable unilamellar liposomes in aqueous media. Beef heart cytochrome c-oxidase could be functionally reconstituted in these liposomes. In the presence of reduced cytochrome c, a protonmotive force (delta p) across the liposomal membrane was generated of up to -92 mV. Upon fusion of these proteoliposomes with membrane vesicles of Lactococcus lactis, the delta p generated by cytochrome c-oxidase activity was capable to drive uphill transport of leucine. Electron microscopic analysis indicated that the tetraether lipids form a single monolayer liposome. The results demonstrate that tetraether lipids of archaebacteria can form a suitable matrix for the function of exogenous membrane proteins originating from a regular lipid bilayer. PMID- 1309770 TI - A role for the passage helix in the DNA cleavage reaction of eukaryotic topoisomerase II. A two-site model for enzyme-mediated DNA cleavage. AB - Eukaryotic topoisomerase II is capable of binding two separate nucleic acid helices prior to its DNA cleavage and strand passage events (Zechiedrich, E. L., and Osheroff, N (1990) EMBO J. 9, 4555-4562). Presumably, one of these helices represents the helix that the enzyme cleaves (i.e. cleavage helix), and the other represents the helix that it passes (i.e. passage helix) through the break in the nucleic acid backbone. To determine whether the passage helix is required for reaction steps that precede the enzyme's DNA strand passage event, interactions between Drosophila melanogaster topoisomerase II and a short double-stranded oligonucleotide were assessed. These studies employed a 40-mer that contained a specific recognition/cleavage site for the enzyme. The sigmoidal DNA concentration dependence that was observed for cleavage of the 40-mer indicated that topoisomerase II had to interact with more than a single oligonucleotide in order for cleavage to take place. Despite this requirement, results of enzyme DNA binding experiments indicated no binding cooperativity for the 40-mer. These findings strongly suggest a two-site model for topoisomerase II action in which the passage and the cleavage helices bind to the enzyme independently, but the passage helix must be present for efficient topoisomerase II-mediated DNA cleavage to occur. PMID- 1309771 TI - In vivo differential prenylation of retinal cyclic GMP phosphodiesterase catalytic subunits. AB - A number of phototransducing proteins in vertebrate photoreceptors contain a carboxyl terminal -CXXX motif (where C = cysteine and X = any amino acid), known to be a signal sequence for their post-translational prenylation and carboxyl methylation. To study the roles of these modifications in the visual excitation process, we have utilized an intravitreal injection method to radiolabel the prenylated proteins of rat retinas in vivo. We showed that two of the major prenylated polypeptides in the rod outer segments are the PDE alpha and PDE beta subunits of cyclic GMP phosphodiesterase PDE alpha and PDE beta subunits of cyclic GMP phosphodiesterase (PDE). By chromatographic analyses of the amino acid constituents generated by exhaustive proteolysis of PDE alpha and PDE beta, we further demonstrated that they are differentially prenylated by farnesylation and geranylgeranylation, respectively. While a number of proteins ending with the CXXX sequence have already been reported to possess either a farnesyl or a geranylgeranyl group, PDE is the first enzyme shown to be modified by both types of prenyl groups. The prenyl modification of PDE most likely plays a major role in membrane attachment and in correctly positioning the PDE molecule for phototransduction. PMID- 1309772 TI - Identification of structural domains in protein C involved in its interaction with thrombin-thrombomodulin on the surface of endothelial cells. AB - The structural domains of protein C involved in its interaction with thrombin thrombomodulin on the endothelial cell surface have been investigated using isolated intact domains of bovine protein C produced from controlled proteolytic digests of the protein. The fragments investigated include the gamma carboxyglutamic acid (Gla)-rich module, the two epidermal growth factor (EGF) like modules, and a fragment consisting of the Gla and the two EGF-like modules. The effects of these fragments on the catalytic efficiency (Km and Vmax) of activation of protein C by the endothelial cell surface thrombin-thrombomodulin complex (IIa-TM) have been evaluated in vitro using a stirred microcarrier cell culture of bovine aortic endothelial cells and purified proteins. Neither the Gla nor the two EGF-like modules alone had any discernible effect on protein C activation. The intact Gla-EGF fragment, however, inhibited protein C activation. The results are consistent with a rapid equilibrium competitive inhibition model, in which the Gla-EGF fragment competes with protein C for binding to IIa-TM, and indicate that the Gla-EGF fragment alone accounts for most of the binding energy of intact protein C for IIa-TM. In addition, a requirement for the Gla residues of protein C for binding is implied by the observation that heat-decarboxylated Gla-EGF fragment was not an inhibitor of protein C activation. In addition, chloromethyl ketone-inactivated activated protein C was found to bind to IIa-TM with the same affinity as protein C, suggesting that the changes which occur in protein C upon activation do not affect that part of the protein responsible for binding to IIa-TM, that is the Gla-EGF region. The Gla-EGF region from factor X also weakly inhibited the IIa-TM activation of protein C. PMID- 1309773 TI - A ubiquitin C-terminal isopeptidase that acts on polyubiquitin chains. Role in protein degradation. AB - In the ubiquitin (Ub) pathway, proteins are ligated with polyUb chains and then are degraded by a 26 S protease complex. We describe an enzyme, called isopeptidase T, that acts on polyUb chains. It is a monomeric Ub-binding protein abundant in erythrocytes and reticulocytes. The activity of the isopeptidase is inhibited by iodoacetamide and Ub aldehyde. Treatment of the enzyme with Ub aldehyde increased its affinity for free Ub, indicating the existence of two different Ub-binding sites and cooperativity between the two sites. Isopeptidase T acts on polyUb-protein conjugates, but not on conjugates in which the formation of polyUb chains was prevented by the use of reductively methylated Ub or on abnormal polyUb chains formed with a mutant Ub that contains a Lys----Arg substitution at residue 48. The enzyme converts high molecular mass polyUb protein conjugates to lower molecular mass forms with the release of free Ub, but not of free protein substrate. The lower molecular mass Ub-protein conjugate products are resistant to further action of the enzyme. Isopeptidase T stimulates protein degradation in a system reconstituted from purified enzyme components. The enzyme also stimulates the degradation of proteins ligated to polyUb chains by the 26 S protease complex. Preincubation of polyUb-protein conjugates with the isopeptidase did not much increase their susceptibility to proteolysis by the 26 S complex. On the other hand, preincubation of conjugates with the 26 S protease complex and ATP increased the release of free Ub upon further incubation with the isopeptidase. It thus seems that a role of this isopeptidase in protein breakdown is to remove polyUb chain remnants following the degradation of the protein substrate moiety by the 26 S complex. PMID- 1309774 TI - Galactose-containing glycosylphosphatidylinositols in Trypanosoma brucei. AB - Many eukaryotic surface glycoproteins, including the variant surface glycoproteins (VSGs) of Trypanosoma brucei, are synthesized with a carboxyl terminal hydrophobic peptide extension that is cleaved and replaced by a complex glycosylphosphatidylinositol (GPI) membrane anchor within 1-5 min of the completion of polypeptide synthesis. We have reported the purification and partial characterization of candidate precursor glycolipids (P2 and P3) from T. brucei. P2 and P3 contain ethanolamine-phosphate-Man alpha 1-2Man alpha 1-6Man alpha 1-GlcN linked glycosidically to an inositol residue, as do all the GPI anchors that have been structurally characterized. The anchors on mature VSGs contain a heterogenously branched galactose structure attached alpha 1-3 to the mannose residue adjacent to the glucosamine. We report the identification of free GPIs that appear to be similarly galactosylated. These glycolipids contain diacylglycerol and alpha-galactosidase-sensitive glycan structures which are indistinguishable from the glycans derived from galactosylated VSG GPI anchors. We discuss the relevance of these galactosylated GPIs to the biosynthesis of VSG GPI anchors. PMID- 1309775 TI - Discoordinate regulation of isoforms of Na,K-ATPase and myosin heavy chain in the hypothyroid postnatal rat heart and skeletal muscle. AB - During postnatal life, many contractile and electrophysiological properties of the rat heart undergo changes. Among the changes is a switch in the expression of Na,K-ATPase catalytic subunit isoforms. Thyroid hormone has been postulated to play an important role in the postnatal transformation of the heart, and its effect on myosin heavy chain isoform gene transcription is well documented. To test whether it controls Na,K-ATPase gene switching in vivo, we made neonatal rats hypothyroid by maternal treatment with methimazole. The expression of Na,K ATPase catalytic subunit isoforms in cardiac and skeletal muscle membranes was measured with specific antibodies at time points from birth to 4 weeks of age. Postnatal changes in Na,K-ATPase isoform expression in cardiac ventricle and hind limb skeletal muscle were similar in control and hypothyroid animals. In the same hypothyroid animals, the postnatal switch from the V3 (beta) isoform of myosin heavy chain to the V1 (alpha) isoform was blocked. The conclusion is that thyroid hormone may have a modulatory role in Na,K-ATPase gene expression, but it is not the developmental signal that dominates gene switching. PMID- 1309776 TI - High and intermediate affinity calmodulin binding domains of the alpha and beta subunits of phosphorylase kinase and their potential role in phosphorylation dependent activation of the holoenzyme. AB - Phosphorylase kinase is a calcium-regulated multimeric enzyme of composition (alpha beta gamma delta)4, which contains calmodulin as the integral delta subunit and also is activated further by addition of extrinsic calmodulin. Previous studies by Dasgupta, M., Honeycutt, T., and Blumenthal, D.K. ((1989) J. Biol. Chem. 264, 17156-17163) have identified gamma 302-326 and gamma 342-366 as two calmodulin binding regions. Using peptides that were synthesized based on alpha and beta primary structure and that were predicted to contain the basic amphiphilic alpha-helix motif thought important for calmodulin binding, four additional potential calmodulin binding domains have now been identified: one of high affinity, beta 770-794; two of intermediate affinity, beta 5-28 and beta 920 946; and one with marginally low affinity, alpha 1070-1093. Peptide beta 770-794 was of higher calmodulin affinity than either gamma 302-326 or gamma 342-366; it was of higher affinity than the model synthetic peptide IV defined by O'Neil, K.T., and DeGrado, W.F. ((1990) Trends Biochem. Sci. 15, 59-64); and it is currently the most potent calmodulin-binding peptide so far described. Correlated with their affinity for calmodulin, all six phosphorylase kinase-derived peptides and several other established calmodulin-binding peptides inhibited phosphorylase kinase previously activated by cAMP-dependent phosphorylation, reducing its activity to the level of the nonactivated enzyme. However, these peptides did not inhibit (and some peptides slightly activated) the nonphosphorylated enzyme. Even in the presence of these peptides both activated and nonactivated enzyme remained fully Ca(2+)-dependent. The beta 770-794 peptide has at least a 5-fold greater calmodulin binding affinity than the holo-phosphorylase kinase. This, and its higher affinity for calmodulin than either of the sites on the gamma subunit, raises the possibility that in the native enzyme it may be involved in binding the intrinsic delta subunit. Further, inhibition of activated but not nonactivated enzyme by calmodulin-binding peptides would suggest that the phosphorylation-dependent activation of phosphorylase kinase may be mediated by changes in the binding interactions of the intrinsic calmodulin delta subunit. PMID- 1309778 TI - The guanine nucleotide-binding protein Gs activates a novel calcium transporter in Xenopus oocytes. AB - Calcium influx is an important aspect of receptor-mediated signal transduction, yet limited information is available regarding the pathways of calcium influx into nonexcitable cells. We show that treatment of oocytes from Xenopus laevis with cholera toxin, a potent activator of the guanine nucleotide-binding protein Gs, specifically stimulates a sustained inward whole cell flux of calcium through a novel membrane transporter. The calcium is distributed into a mobilizable pool. The flux is voltage-independent and is completely and specifically blocked by microinjection of oocytes with an antiserum directed against Gs alpha. The flux is not activated by treatment of the cells with forskolin or 8-bromo-cyclic adenosine monophosphate indicating that the effect of Gs alpha on the transporter occurs independently of adenylylcyclase activation. Transporter activity is insensitive to benzyl amiloride, does not require a sodium gradient, and is not stimulated by external calcium, indicating that it is not a sodium-calcium exchanger. The Gs-activated flux is dramatically potentiated by lanthanum ion and other trivalent cations but not by any of six divalent cations that were tested; all other known calcium channels and exchangers are, in contrast, potently blocked by lanthanum. The divalent cation cadmium inhibited transporter activity in a concentration-dependent manner. This novel calcium transporter may be important for receptor-mediated calcium influx in the oocyte and perhaps other cell types. PMID- 1309777 TI - Ceramide is a competitive inhibitor of diacylglycerol kinase in vitro and in intact human leukemia (HL-60) cells. AB - Prior studies demonstrated that ceramide was phosphorylated by a novel Ca(2+) dependent kinase distinct from diacylglycerol (DG) kinase in human myelogenous leukemia (HL-60) cells (Kolesnick, R. N., and Hemer, M. R. (1990) J. Biol. Chem. 265, 10900-10904). The present studies were initiated to determine whether mammalian DG kinase purified to homogeneity possessed phosphotransferase activity toward ceramide. A high molecular weight rat brain DG kinase demonstrated Mg(2+) (but not Ca(2+)-) dependent DG kinase activity and did not phosphorylate ceramide in the presence of either cation. In contrast, ceramide served as a competitive inhibitor with an inhibition constant (Ki) 2-6-fold greater than the Km for DG. Inhibition was noncompetitive with respect to ATP and Mg2+. A cell-permeable ceramide, N-octanoyl sphingosine (C8-cer), was used to study effects of ceramide on DG kinase in intact HL-60 cells. C8-cer induced dose- and time-dependent increases in cellular DG levels. As little as 1 microM C8-cer increased DG from a basal level of 103 to 177 pmol.10(6) cells-1, and a maximal 2.9-fold elevation to 292 pmol.10(6) cells-1 occurred with 10 microM C8-cer. DG elevation was detected after 1 min, maximal by 7.5 min, and sustained for 30 min. The DG elevation was accompanied by a reduction in 32P incorporation in phosphatidic acid in cells short term-labeled with [32P]orthophosphoric acid, consistent with inhibition of DG kinase. In contrast, a similar elevation in the DG level induced by exogenous phospholipase C increased 32P incorporation into phosphatidic acid. C8-cer was not metabolized to sphingomyelin, indicating that DG was not generated through the phosphatidylcholine:ceramide cholinephosphotransferase reaction. DG elevation after C8-cer or phospholipase C treatment was sufficient to redistribute protein kinase C from cytosol to membrane. These findings provide evidence that ceramide may serve as a competitive inhibitor of DG kinase. PMID- 1309779 TI - Specific N-methylations of HPV-16 E7 peptides alter binding to the retinoblastoma suppressor protein. AB - Complex formation between the human papilloma virus type 16 E7 protein (HPV-16 E7) and the retinoblastoma growth suppressor protein (RB) is believed to contribute to the process of cellular transformation that leads to cervical carcinoma. Genetic analysis of the HPV-16 E7 protein has shown that the segment of E7 homologous to the conserved region 2 of adenovirus 5 E1A protein is involved in both RB binding and E7-mediated cell transformation. We have previously shown that a peptide colinear with HPV-16 E7 residues 21-29 was able to block immobilized species of E7 from binding to RB protein. The current study reports the effects of different chemical modifications of this peptide. One type of modification, methylation of the alpha-amino nitrogens contributed by Leu22, Tyr25, and Leu28, resulted in a 45-fold increase in E7/RB binding antagonist activity. This increased antagonist activity is sequence-specific since methylation of the amino groups contributed by Tyr23, Cys24, or Glu26 resulted in a profound loss of binding antagonist activity. Using a newly developed binding assay we determined that the apparent dissociation constant for recombinant HPV 16 E7 protein binding to recombinant human RB protein is 1.3 nM. The peptide Ac[N MeLeu22,N-Me-Tyr25,N-MeLeu28]-(21-29)-E7 amide was determined to be a competitive inhibitor of HPV-16 E7 binding to RB with a Ki value of 32 nM. PMID- 1309780 TI - Serum regulates Na+/H+ exchange in Caco-2 cells by a mechanism which is dependent on F-actin. AB - Regulation of Na+/H+ exchange by fetal bovine serum was studied in Caco-2 cells, an established cell line derived from a human colon carcinoma. Cells were grown as polarized monolayers on collagen-coated filters and intracellular pH measured fluorometrically with 2',7'-bis(2-carboxymethyl)-5,6-carboxyfluorescein. Na+/H+ exchange was reduced 64% when cells were deprived of serum for 4 h. In contrast to other cell types, readdition of serum for 10 min did not activate Na+/H+ exchange; however, readdition of serum for 4 h restored Na+/H+ exchange to control values. This long-term effect of serum on Na+/H+ exchange activity could not be explained by changes in intracellular buffering capacity or intracellular [Na+]. 4-h serum deprivation reduced the K(t) of the exchanger for external Na+ from 21 to 6 mM, and reduced the V(max) by 57%, but did not alter the IC50 for amiloride in the presence of 140 mM Na+. Inhibition of protein synthesis with cycloheximide (5 microM) did not alter the effect of serum removal or readdition on Na+/H+ exchange. Low temperature (13 degrees C) completely prevented the inhibition of Na+/H+ exchange caused by the removal of serum. In addition, once Na+/H+ exchange was inhibited by serum removal at 37 degrees C, maintaining cells at 13 degrees C also blocked the recovery of Na+/H+ exchange caused by serum readdition. Conversely, cytochalasin D (0.1-20 microM) blocked the reduction of Na+/H+ exchange which occurred due to 4-h serum deprivation, but did not block the restoration of Na+/H+ exchange when the cells were re-exposed to serum for a further 4 h. Colchicine (20 microM) did not alter the effect of serum removal or readdition. These data suggest that serum regulates Na+/H+ exchange activity by a posttranslational mechanism which is dependent on F-actin. PMID- 1309781 TI - Voltage-sensitive Ca2+ channels. PMID- 1309782 TI - Purification and characterization of the carboxyl-terminal transactivation domain of Vmw65 from herpes simplex virus type 1. AB - A glutathione S-transferase fusion to the COOH-terminal acidic transactivation domain of Vmw65 from herpes simplex virus type 1 was overexpressed in Escherichia coli and isolated by affinity chromatography on glutathione-Sepharose. Following cleavage of the fusion protein with thrombin, the transactivation domain was purified to homogeneity by ion exchange chromatography yielding approximately 0.6 mg of protein/liter of bacterial culture. Equilibrium sedimentation analysis showed the purified polypeptide to be monomeric; however, it displayed aberrant electrophoretic and chromatographic properties. Contrary to secondary structure predictions, circular dichroism spectroscopy demonstrated that this transactivation domain was devoid of significant alpha-helical structure at physiological conditions. The polypeptide, however, became notably more structured under hydrophobic conditions or at low pH, suggesting that it was sensitive to its environment. Near-UV circular dichroism suggested that phenylalanyl and tyrosyl residues were under influence from tertiary structure. PMID- 1309783 TI - Rapid optimization of enzyme substrates using defined substrate mixtures. AB - A strategy is described for the rapid optimization of kcat/Km for protease substrates. Selected positions of a given peptide substrate sequence are varied through synthesis with mixtures of amino acids. Incubation of the resulting peptide mixture with the enzyme of interest and analysis by high pressure liquid chromatography provides a direct measure of analogs with enhanced kcat/Km. High performance liquid chromatography/continuous flow fast atom bombardment mass spectrometry is used to assign structure to each peak in the chromatogram. As an example of the utility and efficiency of "substrate mapping" we describe optimization of the collagenase substrate Dnp-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2 (where Dnp is dinitrophenyl) at the P'1 and P'2 positions. Six different mixtures were prepared for evaluation, representing the synthesis of 128 different synthetic substrates. "Substrate mapping" has led to Dnp-Pro-Leu-Gly-Cys(Me)-His Ala-D-Arg-NH2, a substrate that possesses a 10-fold better kcat/Km than Dnp-Pro Leu-Gly-Leu-Trp-Ala-D-Arg-NH2. PMID- 1309784 TI - A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor. AB - A truncated form of the type 1 fibroblast growth factor receptor (FGFR1) lacking most of its cytoplasmic domain was tested for its ability to inhibit signal transduction by each of three different wild-type FGFRs (FGFR1, 2, and 3). When the truncated FGFR1 was expressed in Xenopus oocytes in excess of each wild-type FGFR, mobilization of intracellular calcium mediated by the wild-type FGFRs was completely blocked. The truncated FGFR did not inhibit signal transduction by the co-expressed platelet-derived growth factor beta-receptor. A form of truncated FGFR1 which lacked the first immunoglobulin-like domain also inhibited signal transduction by wild-type FGFRs. Truncated FGFR formed complexes with wild-type FGFR in the presence of basic FGF in intact cells. These observations were consistent with the hypothesis that the truncated FGFR interacted with wild-type FGFRs to form nonfunctional heterodimers, thus eliminating the signaling by the wild-type FGFRs. The observation that signaling by multiple types of FGFR can be blocked by a single type of truncated FGFR suggests that the different types of FGFR can interact with each other in ligand-mediated complexes. These findings provide a molecular basis for inhibiting the actions of FGFs in vivo. PMID- 1309785 TI - Regulated and constitutive secretion. Differential effects of protein synthesis arrest on transport of glycosaminoglycan chains to the two secretory pathways. AB - Many neural and endocrine cells possess two pathways of secretion: a regulated pathway and a constitutive pathway. Peptide hormones are stored in granules which undergo regulated release whereas other surface-bound proteins are externalized constitutively via a distinct set of vesicles. An important issue is whether proper function of these pathways requires continuous protein synthesis. Wieland et al. (Wieland, F.T., Gleason, M.L., Serafini, T.A., and Rothman, J.E. (1987) Cell 50, 289-300) have shown that a tripeptide containing the sequence Asn-Tyr Thr can be glycosylated in intracellular compartments and secreted efficiently from Chinese hamster ovary and HepG2 cells, presumably via the constitutive secretory pathway. Secretion is not affected by cycloheximide, suggesting that operation of this pathway does not require components supplied by new protein synthesis. In this report we determined the effects of protein synthesis inhibitor on membrane traffic to the regulated secretory pathway in the mouse pituitary AtT-20 cells. We examined transport of glycosaminoglycan chains since previous studies have shown that these chains enter the regulated secretory pathways and are packaged along with the hormone adrenocorticotropin (ACTH). We found that cycloheximide treatment severely impairs the cell's ability to store and secrete glycosaminoglycan chains by the regulated secretory pathway. In marked contrast, constitutive secretion of glycosaminoglycan chains remains unhindered in the absence of protein synthesis. The differential requirements for protein synthesis indicate differences in the mechanisms for sorting and/or transport of molecules through the constitutive and the regulated secretory pathways. We discuss the possible mechanisms by which protein synthesis may influence trafficking of glycosaminoglycan chains to the regulated secretory pathway. PMID- 1309786 TI - The purification of a Rap1 GTPase-activating protein from bovine brain cytosol. AB - Two GTPase-activating proteins (GAPs) have been detected in extracts from bovine brain: GAP-1, which is specific for the activation of ras GTPases, and GAP-3, which is specific for the activation of the rap1 GTPases. We present a strategy for the purification to homogeneity of a cytosolic form of GAP-3 from bovine brain. The 100,000 x g supernatant from homogenized brains was chromatographed sequentially on DEAE Fast Flow, green H-E4BD Sepharose, Bio-Gel A1.5, hydroxyapatite, and phenyl-Sepharose prior to high resolution separation on Mono Q HR 5/5, phenyl-Superose HR 5/5, Mono Q PC 1.6/5, and Superose 12 PC 3.2/30. This procedure resulted in an approximately 18,000-fold purification, yielding 50 micrograms of GAP-3 from 1.6 kg of tissue. Purified cytosolic GAP-3 migrated as a single band of apparent Mr 55,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, on gel filtration cytosolic GAP-3 chromatographed as a dimer with an apparent Mr 92,000. Purified GAP-3 does not activate ras or rho GTPases and possesses no intrinsic GTPase activity. Amino acid sequence data indicated a proline-rich N terminus. The amino acid sequences of peptides generated by Staphylococcus aureus V8 digestion of reduced and pyridine-ethylated GAP-3 showed no similarity to the predicted primary structure of GAP-1 or any other proteins in the nucleic acid or protein data bases. By comparison with the data of Rubinfeld et al. (Rubinfeld, B., Munemitsu, S., Clark, R., Conroy, L., Watt, K., Crosier, W.J., McCormick, F., and Polakis, P. (1991) Cell 65, 1033 1042), it appears that the membrane-associated (Mr 85,000-95,000) and cytosolic forms of GAP-3 are derived from equivalent, or closely related, genes. PMID- 1309787 TI - Conversion of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine to 1-O-alk-1'-enyl-2 acyl-sn-glycero-3-phosphoethanolamine. A novel pathway for the metabolism of ether-linked phosphoglycerides. AB - Madin Darby canine kidney (MDCK) cells convert 1-O-[3H]alkyl-2-acyl-sn-glycero-3 phosphocholine [( 3H]alkylacylGPC) to a product tentatively identified as an ethanolamine-containing phosphoglyceride (PE) (Daniel, L. W., Waite, B. M., and Wykle, R. L. (1986) J. Biol. Chem. 261, 9128-9132). In the present study, analysis of the radiolabeled phosphoglycerides as diradylglycerobenzoate derivatives indicated that [3H] alkylacylGPC was initially converted to 1-O [3H]alkyl-2-acyl-sn-glycero-3-phosphoethanolamine [( 3H]alkylacylGPE) which was subsequently desaturated to 1-O-[3H]alk-1'-enyl-2-acyl-sn-glycero-3 phosphoethanolamine [( 3H]alkenylacylGPE). The conversion of [3H]/[32P]alkyl lysoGPC to [3H]alkenylacylGPE indicated that base exchange enzymes were not involved in this pathway. A phosphono analog of alkyl-lysoGPC, resistant to phospholipase D hydrolysis and radiolabeled in the 1-O-alkyl chain was readily incorporated, acylated, and subsequently metabolized to [3H]alkylacylGPC and [3H]alkenylacylGPE. Therefore, the involvement of phospholipase D in the conversion pathway was ruled out. The conversion of [3H]alkylacylGPC or its phosphono analog to [3H]alkenylacylGPE was significantly enhanced by the addition of 100 microM ethanolamine to the culture media, suggesting that [3H]alkylacylglycerol is an intermediate in the cytidine-dependent pathway of PE synthesis. MDCK cell cytosol and microsomes contained no detectable phospholipase C activity. However, incubation of microsomes with CMP resulted in the degradation of [3H]alkylacylGPC and accumulation of [3H]alkylacylglycerol. Furthermore, the addition of CDP-ethanolamine to microsomes following preincubation with CMP, resulted in a decrease in [3H]alkylacylglycerol with a concomitant increase in [3H]alkenylacylGPE. Overall, these results suggest that the reverse reaction of choline phosphotransferase may be responsible for the conversion of alkylacylGPC to alkylacylGPE. PMID- 1309788 TI - Orthophosphate-promoted ouabain binding to Na/K pumps of resealed red cell ghosts. Evidence for E*P preferentially binding ouabain. AB - Modulation of phosphoenzyme forms of the Na/K pump by Na+ and K+ was studied by measuring the rate of Pi-promoted ouabain binding to resealed ghosts made from human red cells. This system permits distinguishing the effects of the ions at intracellular and external binding sites. Internal K+, Ki, inhibited the rate of Pi-promoted ouabain binding, contrary to a prediction based on a current model of the pump. External K+, Ko, failed to inhibit ouabain binding in the absence of Ki. However, Ko enhanced the inhibition by Ki. Nai also inhibited ouabain binding; this inhibition was much less affected by Ko than was inhibition by Ki, suggesting that Ki and Nai affect ouabain binding at different internal sites. Nao inhibited ouabain binding in the absence of Ki or Ko, so Nao and Ko also act at different sites. With Nao present, Ki stimulated ouabain binding. Thus a condition was found in which the predicted stimulation of binding by Ki was observed. The results of this study are interpreted in terms of three phosphoenzyme forms of the pump: E1P, E*P, and E2P. E*P is the form binding ouabain with highest affinity. Ki promotes E*P----E2P, thereby inhibiting ouabain binding. Ko binds only to E2P, therefore Ki is required for inhibition by Ko, and there is little E2P present with no Ki. Nao inhibits binding by stabilizing E1P whereas Nai inhibits by stabilizing E1. The stimulation by Ki with Nao present means that Ki and Nao together favor formation of E*P. Furthermore, Ki and Nao may bind to the pump simultaneously. Ki may play a role in the normal pump cycle, binding at allosteric sites to promote E*P----E2P. PMID- 1309789 TI - Discrete amino acid sequences of the alpha 1-adrenergic receptor determine the selectivity of coupling to phosphatidylinositol hydrolysis. AB - We have constructed a variety of chimeric beta 2/alpha 1 adrenergic receptors (AR) in which selected portions of the third intracellular loop of the alpha (1B)AR were substituted into the corresponding regions of the beta 2AR. The mutant receptors were both transiently and permanently expressed in COS-7 or L cells, respectively, and tested for their ability to mediate epinephrine-induced activation of polyphosphoinositide (PI) hydrolysis and adenylylcyclase. We have determined that 27 amino acids of the alpha (1B)AR (residues 233-259) derived from the N-terminal portion of the third intracellular loop represent the structural determinant conferring to the beta 2AR the ability to activate PI hydrolysis. This finding suggests that in the alpha (1B)AR the N-terminal portion of the third intracellular loop plays a major role in determining the selectivity of receptor-G protein coupling. However, replacement of alpha 1B sequences in the third intracellular loop of the beta 2AR did not abolish the latter receptor's coupling to activation of adenylylcyclase, thus resulting in chimeric adrenergic receptors which activated both PI hydrolysis and adenylylcyclase. These results indicate that, even if the N-terminal portion of the third intracellular loop is a major determinant of the selectivity of receptor-G protein coupling, other structural domains of the receptors also modulate this property. The comparison of the amino acid sequences which determine the selectivity of G protein coupling in functionally similar receptors may help to elucidate the structural basis for activation of specific G protein-effector systems. PMID- 1309790 TI - A tyrosinated peptide representing the alternatively spliced exon of the platelet derived growth factor A-chain binds specifically to cultured cells and interferes with binding of several growth factors. AB - Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin. Alternative exon splicing is responsible for two forms of the PDGF A-chain which differ at the carboxyl terminus by a highly basic region consisting of 18 amino acids. To clarify the function of the region, we synthesized an octadecapeptide corresponding to this extension (A194-211), incorporated a tyrosine residue at the amino terminus, and used the radioiodinated construct in binding studies with Balb/c3T3 cells and a variety of human cell lines. 125I-(Y)A194-211 bound specifically, reversibly, saturably, and with low affinity to a large population of binding sites on these cells. In addition, (Y)A194-211 markedly reduced the binding of its parent protein, 125I PDGF-AAL, to its receptor. (Y)A194-211 also attenuated the binding of epidermal growth factor and several other isoforms of PDGF, but did not interfere with the binding of transferrin to its receptor. These observations were not due to competitive binding of peptide directly to known receptors for the respective growth factors, but was likely due to interaction of (Y)A194-211 with extracellular glycosaminoglycan. Thus, A194-211 may represent an additional heparin binding domain on mature PDGF-AAL, and as an isolate, is capable of modulating interactions between several potent growth factors and their respective receptors. PMID- 1309791 TI - The reactivity of thiols and disulfides with different redox states of myoglobin. Redox and addition reactions and formation of thiyl radical intermediates. AB - The reactivity of several thiols, including glutathione, dihydrolipoic acid, cysteine, N-acetyl cysteine, and ergothioneine, as well as several disulfides, toward different redox states of myoglobin, mainly met-myoglobin (HX-FeIII) and ferrylmyoglobin (HX-FeIV=O), was evaluated by optical spectral analysis, product formation, and thiyl free radical generation. Only dihydrolipoic acid reduced met myoglobin to oxy-myoglobin, whereas all the other thiols tested did not interact with met-myoglobin. Although the redox transitions involved in the former reduction were expected to yield the dihydrolipoate thiyl radical, the reaction was EPR silent. Conversely, all thiols interacted to different extent with the high oxidation state of myoglobin, i.e. ferrylmyoglobin, via two processes. First, direct electron transfer to heme iron in ferrylmyoglobin (HX-FeIV=O) with formation of met-myoglobin (HX-FeIII) or oxymyoglobin (HX-FeIIO2); the former transition was effected by all thiols except dihydrolipoate, which facilitated the latter, i.e. the formation of the two-electron reduction product of ferrylmyoglobin. Second, nucleophilic addition onto a pyrrole in ferrylmyoglobin with subsequent formation of sulfmyoglobin. The contribution of either direct electron transfer to the heme iron or nucleophilic addition depended on the physicochemical properties of the thiol involved and on the availability of H2O2 to reoxidize met-myoglobin to ferrylmyoglobin. The thiyl radicals of glutathione, cysteine, and N-acetylcysteine were formed during the interaction of the corresponding thiols with ferrylmyoglobin and detected by EPR in conjunction with the spin trap 5,5'-dimethyl-1-pyroline-N-oxide. The intensity of the EPR signal was insensitive to superoxide dismutase and it was decreased, but not suppressed, by catalase. The disulfides of glutathione and cysteine did not react with ferrylmyoglobin, but the disulfide bridge in lipoic acid interacted efficiently with the ferryl species by either reducing directly the heme iron to form met myoglobin or adding onto a pyrrole ring to form sulfmyoglobin; either process depended on the presence or absence of catalase (to eliminate the excess of H2O2) in the reaction mixture, respectively. The biological significance of the above results is discussed in terms of the occurrence and distribution of high oxidation states of myoglobin, its specific participation in cellular injury, and its potential interaction with biologically important thiols leading to either recovery of myoglobin or generation of nonfunctional forms of the hemoprotein as sulfmyoglobin. PMID- 1309792 TI - Cloning of the vaccinia virus ribonucleotide reductase small subunit gene. Characterization of the gene product expressed in Escherichia coli. AB - During its infectious cycle, vaccinia virus expresses a virus-encoded ribonucleotide reductase which is distinct from the host cellular enzyme (Slabaugh, M.B., and Mathews, C.K. (1984) J. Virol. 52, 501-506; Slabaugh, M.B., Johnson, T.L., and Mathews, C.K. (1984) J. Virol. 52, 507-514). We have cloned the gene for the small subunit of vaccinia virus ribonucleotide reductase (designated VVR2) into Escherichia coli and expressed the protein using a T7 RNA polymerase plasmid expression system. After isopropyl beta-D thiogalactopyranoside induction, accumulation of a 37-kDa peptide was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and this peptide reacted with polyclonal antiserum raised against a TrpE-VVR2 fusion protein. The 37-kDa protein was purified to homogeneity, and gel filtration of the purified protein revealed that the recombinant protein existed as a dimer in solution. Purified recombinant VVR2 protein was shown to complement the activity of purified recombinant ribonucleotide reductase large subunit, with a specific activity that was similar to native VVR2 from a virus-infected cell extract. A CD spectrum of the recombinant viral protein showed that like the mouse protein, the vaccinia virus protein has 50% alpha-helical structure. Like other iron containing ribonucleotide reductase small subunits, recombinant VVR2 protein contained a stable organic free radical that was detectable by EPR spectroscopy. The EPR spectrum of purified recombinant VVR2 was identical to that of vaccinia virus-infected mammalian cells. Both the hyperfine splitting character and microwave saturation behavior of VVR2 were similar to those of mouse R2 and distinct from E. coli R2. By using amino acid analysis to determine the concentration of VVR2, we determined that approximately 0.6 radicals were present per R2 dimer. Our results indicate that vaccinia virus small subunit is similar to mammalian ribonucleotide reductases. PMID- 1309793 TI - Enzymatic effects of a lysine-to-glutamine mutation in the ATP-binding consensus sequence in the RecD subunit of the RecBCD enzyme from Escherichia coli. AB - The RecBCD-K177Q enzyme has a lysine-to-glutamine mutation in the putative ATP binding sequence of the RecD protein (Korangy, F., and Julin, D.A. (1992) J. Biol. Chem. 267, 1727-1732). We have compared the enzymatic properties of the RecBCD-K177Q enzyme with those of the wild-type RecBCD enzyme from Escherichia coli. The purified RecBCD-K177Q enzyme has ATP-dependent nuclease activity on double-stranded or denatured DNA which is reduced (4-14-fold less) compared with the wild type. The kcat and Km(ATP) for ATP hydrolysis stimulated by double stranded DNA are both reduced in RecBCD-K177Q, so that kcat/Km(ATP) is relatively unaffected. The mutant enzyme is impaired in its ability to unwind DNA in an assay where single-stranded DNA is trapped by the single-stranded DNA binding protein and subsequently degraded by S1 nuclease. The mutant enzyme also produces fewer acid-soluble DNA nucleotides per ATP hydrolyzed than does the wild type, at low ATP concentrations (less than 20 microM). PMID- 1309794 TI - Ethanol induces 2',5'-oligoadenylate synthetase and antiviral activities through interferon-beta production. AB - We demonstrate here that ethanol, in contrast to heat shock (Chousterman, S., Chelbi-Alix, M.K., and Thang, M.N. (1987) J. Biol. Chem. 262, 4806-4811), induces interferon (IFN) synthesis and its related activities in Madin-Darby bovine kidney (MDBK) cells. The induced IFN is secreted maximally at 6 h, whereas the induction of 2',5'-oligoadenylate synthetase mRNA peaks between 9 and 12 h and its activity at 15 h. The appearance of both 2',5'-oligoadenylate synthetase activity and the antiviral state upon ethanol treatment is prevented by anti bovine recombinant IFN-beta antibodies. Bovine diarrhea virus infection-free MDBK cells cultured in medium supplemented with serum substitute also gave similar results, thus indicating that IFN synthesis induced by ethanol is not mediated by the activation of bovine diarrhea virus. Together, these results show that: 1) ethanol induces the 2',5'-oligoadenylate synthetase and antiviral activities through IFN-beta production; and 2) the IFN produced does not act directly from inside the cells, but has to be first secreted to bind to its receptor. In MDBK cells, ethanol induces the synthesis of the 70-kDa protein, which precedes the expression of 2',5'-oligoadenylate synthetase; moreover, the transient nature of the synthesis of the hsp 70 in these cells is similar after both heat shock and ethanol treatment. PMID- 1309795 TI - Evidence that cyclic AMP-induced inhibition of phosphatidylcholine biosynthesis is caused by a decrease in cellular diacylglycerol levels in cultured rat hepatocytes. AB - The mechanism by which glucagon and cAMP analogues inhibit phosphatidylcholine biosynthesis was investigated in rat hepatocytes. The studies were facilitated by preparation of an antibody to a synthetic peptide (D-F-V-A-H-D-D-I-P-Y-S-S-A) corresponding to residues 164-176 of CTP:phosphocholine cytidylyl-transferase. The antibody, which was purified by affinity chromatography, quantitatively immunoprecipitated cytidylyltransferase from rat liver cytosol. Various analogues of cAMP had no effect on the labeling of cytidylyltransferase with 32Pi in rat hepatocytes. Nor did the cAMP analogues have any effect on the distribution of cytidylyltransferase between cytosol and membranes. These results indicate that the supply of CDP-choline does not limit phosphatidylcholine biosynthesis in hepatocytes treated with cAMP analogues. A decreased supply of diacylglycerol was considered as an alternative mechanism for inhibition of phosphatidylcholine biosynthesis. An approximately 30% decrease in diacylglycerol concentration was observed in hepatocytes treated with the cAMP analogues or glucagon, compared with controls. A similar decrease of phosphatidylcholine biosynthesis was observed. The cAMP-mediated decrease in diacylglycerol levels and inhibition of phosphatidylcholine biosynthesis were reversed by addition of 0.5-1.5 mM oleic acid to the treated hepatocytes. A correlation coefficient of 0.93 was calculated between the levels of diacylglycerol and the rate of phosphatidylcholine biosynthesis. In another approach, the diacylglycerol levels were increased by an inhibitor of diacylglycerol lipase (U-57908) which also reversed the cAMP effects on diacylglycerol levels and phosphatidylcholine biosynthesis. We conclude that the cAMP-mediated inhibition of phosphatidylcholine biosynthesis was not due to an effect on the phosphorylation of cytidylyltransferase. Instead, phosphatidylcholine biosynthesis appears to be inhibited due to a decreased level of diacylglycerol, a substrate for CDP-choline: 1,2-diacylglycerol cholinephosphotransferase. PMID- 1309796 TI - Functional determinants in the autoinhibitory domain of calcium/calmodulin dependent protein kinase II. Role of His282 and multiple basic residues. AB - Important determinants in the autoinhibitory domain of calcium/calmodulin dependent protein kinase II (CaMK-II), corresponding to residues 281-302 of the kinase alpha-subunit sequence, were identified. Replacement of Thr286 with Ala (CaMK-(281-302 Ala286)) had no effect on either the potency (IC50 = 2 MicroM) or inhibitory mechanism (competitive with ATP) using the catalytic fragment of CaMK II. Single replacement of charged residues in CaMK-(281-302, Ala286) identified His282, Arg283, Lys291, Arg297, and Lys298 as important determinants (greater than 10-fold increase in IC50) for potent inhibition of CaMK-II. Glu285, Asp288, Lys291, Arg296, and Lys300 were not as essential (less than 4-fold change in IC50) for potent CaMK-II inhibition. Replacement of either Arg283, Lys291, or Arg297, and Lys298 with Ala did not alter the ATP-competitive mechanism of inhibition although the Ki values increased 16-530-fold. However, replacement of His282 with Ala decreased the IC50 by 20-fold and altered the mechanism of inhibition to noncompetitive with respect to ATP. The non-protonated form of His282 was functionally active since decreasing the pH from 7.5 to 5.5 increased the IC50 of CaMK-(281-302, Ala286) almost 20-fold. Histidine protonation also appeared to disrupt the autoinhibitory domain of intact forms of CaMK-II since preincubation of non-proteolyzed rat brain CaMK-II with calcium/calmodulin (in the absence of ATP) at pH 5.5 generated up to 16% calcium-independent activity when assayed at pH 5.5. Similarly, the level of calcium-independent activity of a baculovirus-expressed Asp286 mutant CaMK-II ((D286)mCaMK alpha) increased to almost 80% calcium independence when assayed at pH 5.5 compared to only 20% when assayed at pH 7.5. The levels of calcium-independent activity of both the (D286)mCaMK alpha (at pH 5.5 and 7.5) and the rat brain CaMK-II (at pH 5.5) were sensitive to the concentrations of both ATP and peptide substrate (syntide-2) in the assays. These data suggest that the basic residues Arg283, Lys291, Arg297, and Lys298 are important for potent inhibition of CaMK-II and that the non protonated form of His282 may play a unique role in the ATP-directed mechanism of inhibition by the CaMK-II autoinhibitory domain. PMID- 1309797 TI - Defining the involvement of HOCl or Cl2 as enzyme-generated intermediates in chloroperoxidase-catalyzed reactions. AB - Peroxidatic substrates, catechol (CAT) and 2,4,6-trimethylphenol (TMP) were used as probes of thechloride dependent reactions catalyzed by chloroperoxidase (CPO). TMP is consumed only in the presence of chloride. TMP is a competitive inhibitor versus CAT, but CAT is a noncompetitive inhibitor versus TMP in chloride dependent CPO-catalyzed peroxidation reactions. The ratio of TMP versus CAT consumed by the chloride-dependent CPO reaction in direct competition studies increases as the chloride concentration is increased from 1.0 to 400 mM. Ratios of non-enzymatic HOCl reactions under conditions otherwise similar to those of the CPO reactions are relatively insensitive to changes in chloride concentration and are experimentally indistinguishable from the values attained by the enzyme system at high chloride concentrations. Comparison of enzymatic ratios with those of the HOCl reactions indicate that the proportion of the enzymatic reaction involving a freely dissociable, enzyme-generated, oxidized halogen species varies from 10% at low chloride concentrations to essentially 100% at high chloride concentrations. All data are consistent with a mechanism in which chloride competes with CAT for binding to both CPO compound I and the CPO chlorinating intermediate (EOCl). Chloride binding to CPO compound I leads to the formation of EOCl and initiates the CPO chloride-dependent pathway. When CAT binds to either compound I or EOCl, it is directly oxidized to product. When chloride binds to EOCl, it either induces release of HOCl or reacts with EOCl to produce Cl2, which is released from the enzyme. TMP and CAT compete for reaction with the free oxidized halogen species. This is the first direct evidence for kinetically significant involvement of a free oxidized halogen species as an intermediate in any CPO-catalyzed reaction. PMID- 1309798 TI - Coexpression of human cAMP-specific phosphodiesterase activity and high affinity rolipram binding in yeast. AB - Studies by various investigators have demonstrated that the low Km, cAMP-specific phosphodiesterase (PDE IV) is selectively inhibited by a group of compounds typified by rolipram and Ro 20-1724. In addition to inhibiting the catalytic activity of PDE IV, rolipram binds to a high affinity binding site present in brain homogenates. Although it has been assumed that the high affinity rolipram binding site is PDE IV, no direct evidence has been produced to support this assumption. The present studies were undertaken to determine whether the rolipram binding site is coexpressed with PDE IV catalytic activity in Saccharomyces cerevisiae genetically engineered to express human recombinant monocytic PDE IV (hPDE IV). Expressing hPDE IV cDNA in yeast resulted in a 20-fold increase in PDE activity that was evident within 1 h of induction and reached a maximum by 3-6 h. The recombinant protein represented hPDE IV as judged by its immunoreactivity, molecular mass (approximately 88 kDa), kinetic characteristics (cAMP Km = 3.1 microM; cGMP Km greater than 100 microM), sensitivity to rolipram (Ki = 0.06 microM), and insensitivity to siguazodan (PDE III inhibitor) and zaprinast (PDE V inhibitor). Saturable, high affinity [3H] (R)-rolipram-binding sites (Kd = 1.0 nM) were coexpressed with PDE activity, indicating that both binding activity and catalytic activity are properties of the same protein. A limited number of compounds were tested for their ability to inhibit hPDE IV catalytic activity and compete for [3H](R)-rolipram binding. Analysis of the data revealed little correlation (r2 = 0.35) in the structure-activity relationships for hPDE IV inhibition versus competition for [3H] (R)-rolipram binding. In fact, certain compounds (e.g. (R)-rolipram Ro 20-1724) possessed a 10-100-fold selectivity for inhibition of [3H] (R)-rolipram binding over hPDE IV inhibition, whereas others (e.g. dipyridamole, trequinsin) possessed a 10-fold selectivity for PDE inhibition. Thus, although the results of these studies demonstrate that hPDE IV activity and high affinity [3H](R)-rolipram binding are properties of the same protein, they do not provide clear cut evidence linking the binding site with the PDE inhibitory activity of rolipram and related compounds. PMID- 1309800 TI - Glucose 6-phosphate and hexokinase can be used as an ATP-regenerating system by the Ca(2+)-ATPase of sarcoplasmic reticulum. AB - In the presence of hexokinase, vesicles derived from the sarcoplasmic reticulum of skeletal muscle are able to accumulate Ca2+ in a medium containing ADP and glucose 6-phosphate. No significant Ca2+ uptake is observed if one of these components is omitted from the assay medium. Due to its high affinity for ATP, the Ca(2+)-ATPase can use the very low concentrations of ATP formed from glucose 6-phosphate and ADP to form a Ca2+ gradient. This finding indicates that glucose 6-phosphate and hexokinase can be used as an ATP-regenerating system. The Ca2+ uptake supported by glucose 6-phosphate and ADP is inhibited by glucose and D xylose. Half-maximal inhibition is observed in the presence of 0.4 mM glucose and 100 mM D-xylose. The transport ratio (Ca2+ transported:substrate utilized) is the same for glucose 6-phosphate and ATP. The Ca2+ gradient formed when glucose 6 phosphate and ADP are the substrates can be used to synthesize ATP from ADP and Pi. The concentration of ATP formed after reversal of the Ca2+ pump is much higher than that expected from direct equilibration of the reaction between glucose 6-phosphate and ADP. PMID- 1309799 TI - Activation of phospholipase C by the alpha subunits of the Gq and G11 proteins in transfected Cos-7 cells. AB - High efficiency transient transfection was used to introduce cDNA corresponding to various G protein alpha subunits into Cos-7 cells. The proteins that were subsequently synthesized were detected with specific G protein alpha subunit antipeptide antiserum and were localized in the membrane fraction of the cell. Cells that were prelabeled with the [3H]inositol and transfected with G alpha q and G alpha 11 cDNA showed marked increases in formation of [3H]inositol phosphates after stimulation with aluminum fluoride. Co-transfection with cDNAs corresponding to phosphoinositide specific phospholipase C beta 1 (PI-PLC beta 1) and to G alpha q or G alpha 11 resulted in even higher levels of inositol phosphate formation. The introduction of mutations that convert residue glutamine 209 to leucine in G alpha q and G alpha 11 resulted in persistent activation of PI-PLC and high steady state levels of inositol phosphates. On the other hand, transfection with a variety of other G alpha subunit cDNAs, i.e. G alpha Z, G alpha OA, G alpha OB, transducin, and the glutamine 205 to leucine mutants of G alpha Z and of G alpha OA did not increase inositol phosphate formation. To further test the specificity of G protein activation of PI-PLC, a cell-free system was prepared by using washed membranes of transiently transfected cells and purified PI-PLC beta 1. Membranes derived from G alpha q and G alpha 11, but not G alpha OA transfected cells, showed guanosine 5-O-thiotriphosphate (GTP gamma S)-stimulated PIP2 hydrolysis. The activity seen in the system reconstituted with membranes derived from G alpha 11-transfected cells was blocked by preincubation with specific G alpha 11 antipeptide antibodies. All of these results are consistent with the conclusion that G alpha q and G alpha 11 cDNA encode proteins that in the presence of GTP gamma S specifically activate PI PLC. PMID- 1309801 TI - Novel flavonol 3-sulfotransferase. Purification, kinetic properties, and partial amino acid sequence. AB - A flavonol sulfotransferase (EC 2.8.2.-), which catalyzes the transfer of the sulfate group from 3'-phosphoadenosine 5'-phosphosulfate to the 3-hydroxyl group of flavonol aglycones, has been purified to apparent homogeneity from Flaveria chloraefolia. The specific activity of flavonol 3-sulfotransferase was enriched 2000-fold, as compared with the homogenate, with a recovery of 9%. The molecular mass of the native and denatured enzyme was found to be 34.5 kDa, suggesting that the active from of the enzyme is a monomer. The enzyme exhibited expressed specificity for position 3 of flavonol aglycones, showed two activity optima at pH 6.0 and 8.5, did not require divalent cations, and was not inhibited by either EDTA or sulfhydryl group reagents. The results of substrate interaction kinetics and product inhibition are consistent with an Ordered Bi Bi mechanism where 3' phosphoadenosine 5'-phosphosulfate is the first substrate to bind to the enzyme and 3'-phosphoadenosine 5'-phosphate is the final product to be released. The amino acid sequence of two peptides representing 17 and 33 amino acids showed no significant sequence similarity with the amino acid sequences reported for animal sulfotransferases. Antibodies raised against F. chloraefolia 3-sulfotransferase were found to cross-react with the 3'- and 4'-sulfotransferase activities of the same plant, suggesting that the three enzymes are structurally related. PMID- 1309802 TI - Constitutive presence of a catalytic fragment of protein kinase C epsilon in a small cell lung carcinoma cell line. AB - Protein kinase C (PKC) has been implicated in a variety of cellular responses such as proliferation, differentiation, and secretion. We assessed the role of PKC in the mitogenic effects of gastrin-releasing peptide (in a small cell lung cancer (SCLC) cell line. Using antisera that specifically recognize the PKC isoforms alpha, beta, gamma, delta, and epsilon, we determined that PKC epsilon is the major isoform in the SCLC cell line NCI-N417, followed by PKC alpha and delta. In addition to the 90-kDa PKC epsilon, our anti-PKC epsilon antiserum specifically detected a 40-kDa immunoreactive protein. Treatment of the cells with either 20 nM phorbol myristate acetate or 50 nM GRP enhanced significantly the level of the 40-kDa protein in a time-dependent (1-8 h), cycloheximide sensitive fashion. Subcellular fractionation revealed that 90% of PKC epsilon was in particulate form, while the 40-kDa immunoreactive protein was cytosolic. To test the hypothesis that the 40-kDa soluble protein represented a catalytically independent PKC epsilon fragment, cytosolic extracts were assayed for kinase activity. 45-50% of the activity was apparent in the absence of the PKC activators phosphatidylserine and diacylglycerol. This effector-independent kinase activity was further purified by affinity chromatography using a synthetic peptide corresponding to the pseudosubstrate region of PKC epsilon (ERMRPRKRQGAVRRRV) coupled to Sepharose. The partially purified protein, recognized by the anti-PKC epsilon antiserum, exhibited histone kinase activity with kinetics similar to those of the tryptically generated catalytic fragment of brain PKC epsilon. This activity was inhibited by staurosporine (IC50 = 1 x 10( 8) M) and by the pseudosubstrate inhibitor peptide (IC50 = 7.7 x 10(-8) M). The SCLC kinase and the brain PKC epsilon catalytic fragment were similar as indicated by the relative sizes of the PKC epsilon immunoreactive peptides generated with protease V8 from Staphylococcus aureus (Mr approximately 37,000, 34,000, 28,000, 26,000, and 25,000). Taken together, we conclude that a variant SCLC cell line expresses a constitutively active catalytic fragment of PKC epsilon. Regulation by 12-O-tetradecanoyl-13-acetate or GRP via de novo protein synthesis suggests a novel mechanism of control of PKC diversity with implications for small cell lung cancer and possibly other malignancies. PMID- 1309803 TI - A mutant of 7SL RNA in Yarrowia lipolytica affecting the synthesis of a secreted protein. AB - The yeast Yarrowia lipolytica contains two genes, SCR1 and SCR2, encoding a 7SL RNA associated with a signal recognition particle (SRP). To study 7SL RNA function in vivo we have systematically substituted the two conserved nucleotides G128 and A130 in loop 1 of SCR2-encoded 7SL RNA. All single mutations in either nucleotide have no effect. All double mutations are lethal except for one which results in temperature-sensitive growth. We have studied the synthesis and secretion of an alkaline extracellular protease (AEP) in both wild-type and temperature-sensitive mutant strains. Pulse-chase labeling and immunoprecipitation of this protein show that: 1) total protein synthesis is not affected in the mutant strain; 2) levels of AEP precursors in the mutant strain are 60% less than in the wild-type strain; 3) for both strains there is no accumulation of the AEP precursors in the cytoplasm; 4) the kinetics of secretion is similar. These results suggest that mutated SRP is deficient in membrane targeting but still performs translational arrest. This is consistent with the functions of SRP observed in vitro and represents the first demonstration of such roles in vivo. PMID- 1309804 TI - The role of the N terminus in Tet repressor for tet operator binding determined by a mutational analysis. AB - The N-terminal residues preceding the alpha-helix-turn-alpha-helix motif on the Tn10 Tet repressor protein were probed by oligonucleotide-directed deletion mutagenesis for their role in protein activity. All deletion mutants showed decreased repression in vivo, emphasizing the importance of the N terminus for tet operator binding. Only two of the mutants, TetR delta 2-23 and TetR delta 3-8 displayed a reduced intracellular protein level. The remaining deletion mutants showed either reduced binding to tet operator and inducibility by tetracycline or transdominance. We conclude that these deletions do not affect stability and overall protein structure. DNA binding activities of residue-wise increasing deletions, TetR delta 9 through TetR delta 9-13, reveal a pattern consistent with an alpha-helical structure of the affected residues. This conclusion is supported by the helical wheel projection and the hydrophobic moment profile calculated for the protein segment ranging from residues S7-V20. We propose that these residues form an amphipathic alpha-helix which packs closely against the alpha-helix-turn alpha-helix motif and is essential for Tet repressor activity. The residues preceding this putative alpha-helix contribute to DNA binding, but no direct interactions with base pairs of tet operator were revealed in a loss of contact analysis. Individual mutation of the 4 charged residues to alanine at the N terminus shows that no single residue can account for the reduction in repression observed for the deletion mutants. PMID- 1309805 TI - A cdc2-related kinase oscillates in the cell cycle independently of cyclins G2/M and cdc2. AB - The Eg1 gene in Xenopus laevis is related in sequence to the cdc2+ gene. We show here that the Eg1 gene product (cdk2) possesses histone H1 protein kinase activity and binds to PSTAIR antibodies as well as to Sepharose beads linked to the 13-kDa product of the suc 1 gene (p13suc1). Eg1 protein kinase is active only in an Mr approximately 200,000 complex with other proteins but is not associated with any of the three known Xenopus mitotic cyclins or with any newly synthesized protein in egg extracts that exhibit cell cycle oscillations in vitro. The protein kinase activity of Eg1 oscillates in the mitotic cell cycle, being high in M-phase and low in interphase. Hyperactivation of cdc2 kinase by the addition of cyclin A has no effect on the activity or oscillatory behavior of Eg1. Inhibition of cdc2 kinase activation by emetine or RNase treatment of oscillating extracts does not inhibit the activation of Eg1 but does block deactivation normally seen during exit from mitosis. These results indicate that Eg1 is regulated by a cell cycle clock independently of cyclin and cdc2 kinase. PMID- 1309806 TI - Localized Ca2+ entry preferentially effects protein dephosphorylation, phosphorylation, and glutamate release. AB - The release of neurotransmitter glutamate from isolated nerve terminals (synaptosomes) was found to be tightly coupled to the entry of Ca2+ through voltage-dependent Ca2+ channels, but is relatively unresponsive to "bulk" increases in cytosolic Ca2+ concentrations ([Ca2+]c) effected by Ca2+ ionophore. Under the same conditions, this dependence on Ca2+ influx, specifically through Ca2+ channels, was also seen for the dephosphorylation of a 96-kDa protein, (P96), present in the nerve terminals, as well as the phosphorylation of proteins migrating at 75 kDa (P75), corresponding to the synapsins, a group of well characterized synaptic vesicle-associated proteins. P96 dephosphorylation, following Ca2+ influx, was persistent and insensitive to the phosphatase inhibitor okadaic acid, suggesting a phosphatase other than protein phosphatase 1 and 2A as being responsible. Perhaps through the same phosphatase activity the increase in P75 phosphorylation was rapidly reversed with a time course similar to P96 dephosphorylation. When release, P96 dephosphorylation, and P75 phosphorylation were considered as functions of the [Ca2+]c increases achieved by depolarization and Ca2+ ionophore, there was no correlation of any of these with the overall concentration of Ca2+ in the cytosol. Since the fura-2 method used to measure [Ca2+] gives an averaged [Ca2+]c, these results imply that the release and protein dephosphorylation events are functionally coupled to local [Ca2+]c, in the immediate vicinity of Ca2+ channels. The reported clustering of the latter at the active zone area of the synapse and the parallelism between synaptic vesicle exocytosis and the phosphorylation of synaptic vesicle-associated proteins (p75:synapsins Ia/Ib), suggests that P96 may be similarly localized at the active zone area and, therefore, may be of significance in a modulatory role in glutamate release. PMID- 1309807 TI - Purification and initial characterization of peptidyl-tRNA hydrolase from rabbit reticulocytes. AB - We have identified an activity in rabbit reticulocyte lysate as peptidyl-tRNA hydrolase, based upon its ability to hydrolyze native reticulocyte peptidyl-tRNA, isolated from polyribosomes, and N-acylaminoacyl-tRNA, and its inability to hydrolyze aminoacyl-tRNA, precisely the same substrate specificity previously reported for peptidyl-tRNA hydrolase from bacteria or yeast. The physiological role of the reticulocyte enzyme may be to hydrolyze and recycle peptidyl-tRNA that has dissociated prematurely from elongating ribosomes, as suggested for the bacterial and yeast enzymes, since reticulocyte peptidyl-tRNA hydrolase is completely incapable of hydrolyzing peptidyl-tRNA that is still bound to polyribosomes. We have purified reticulocyte peptidyl-tRNA hydrolase over 5,000 fold from the postribosomal supernatant with a yield of 14%. The purified product shows a 72-kDa band upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis that has co-purified with enzyme activity and comprises about 90% of the total stained protein, strongly suggesting that the 72-kDa protein is the enzyme. Sucrose density gradient analysis indicates an apparent molecular mass for the native enzyme of 65 kDa, implying that it is a single polypeptide chain. The enzyme is almost completely inactive in the absence of a divalent cation: Mg2+ (1-2 mM) promotes activity best, Mn2+ is partly effective, and Ca2+ and spermidine are ineffective. The hydrolase shows a Km of 0.60 microM and Vmax of 7.1 nmol/min/mg with reticulocyte peptidyl-tRNA, a Km of 60 nM and Vmax of 14 nmol/min/mg with Escherichia coli fMet-tRNA(fMet), and a Km of 100 nM and Vmax of 2.2 nmol/min/mg with yeast N-acetyl-Phe-tRNA(Phe). The enzyme has a pH optimum of 7.0-7.25, it is inactivated by heat (60 degrees C for 5 min), and its activity is almost completely inhibited by pretreatment with N-ethylmaleimide or incubation with 20 mM phosphate. The fact that the enzyme hydrolyzes E. coli but not yeast or reticulocyte fMet-tRNA(fMet) may be explained, at least in part, by structural similarities between prokaryotic tRNA(fMet) and eukaryotic elongator tRNA that are not shared by eukaryotic tRNA(fMet). PMID- 1309808 TI - Identification of heme and copper ligands in subunit I of the cytochrome bo complex in Escherichia coli. AB - The cytochrome bo complex is a terminal ubiquinol oxidase in the aerobic respiratory chain of Escherichia coli (Kita, K., Konishi, K., and Anraku, Y. (1984) J. Biol. Chem. 259, 3368-3374) and functions as a proton pump. It belongs to the heme-copper oxidase superfamily with the aa3-type cytochrome c oxidases in mitochondria and aerobic bacteria. In order to identify ligands of hemes and copper, we have substituted eight conserved histidines in subunit I by alanine and, in addition, His-106, -284, and -421 by glutamine and methionine. Western immunoblotting analysis showed that all the mutations do not affect the expression level of subunit I in the cytoplasmic membrane, indicating that these histidines are not crucial for its stability. A single copy expression vector carrying a single mutation at the invariant histidines, His-106, His-284, His 333, His-334, His-419, and His-421, of subunit I was unable to support the aerobic growth of a strain in which the chromosomal terminal oxidase genes (the cyo and cyd operons) have been deleted. The same mutations caused a complete loss of ubiquinol oxidase activity of the partially purified enzymes. Spectroscopic analysis of mutant oxidases in the cytoplasmic membrane revealed that substitutions of His-106 and -421 specifically eliminated a 563.5 nm peak of the low spin heme and that replacements of His-106, -284, and -419 reduced the extent of the CO-binding high spin heme. These spectroscopic properties of mutant oxidases were further confirmed with partially purified preparations. Atomic absorption analysis showed that substitutions of His-106, -333, -334, and -419 eliminated CuB almost completely. Based on these findings, we conclude that His 106 and -421 function as the axial ligands of the low spin heme and His-284 is a possible ligand of the high spin heme. His-333, -334, and -419 residues are attributed to the ligands of CuB. We present a helical wheel model of the redox center in subunit I, which consists of the membrane-spanning regions II, VI, VII, and X, and discuss the implications of the model. PMID- 1309809 TI - Determination of the ligands of the low spin heme of the cytochrome o ubiquinol oxidase complex using site-directed mutagenesis. AB - The cytochrome o complex of Escherichia coli is a ubiquinol oxidase which is the predominant respiratory terminal oxidase when the bacteria are grown under high oxygen tension. The amino acid sequences of three of the subunits of this quinol oxidase reveal a substantial relationship to the aa3-type cytochrome c oxidases. The two cytochrome components (b563.5 and o) and the single copper (CuB) present in the E. coli quinol oxidase appear to be equivalent to cytochrome a, cytochrome a3, and CuB of the aa3-type cytochrome c oxidases, respectively. These three prosthetic groups are all located within subunit I of the oxidase. Sequence alignments indicate only six totally conserved histidine residues among all known sequences of subunit I of the cytochrome c oxidases of various species plus the E. coli quinol oxidase. Site-directed mutagenesis has been used to change each of these totally conserved histidines with the presumption that two of these six must ligate to the low spin cytochrome center of the E. coli oxidase. The presence of the low spin cytochrome b563.5 component of the oxidase can be evaluated both by visible absorbance properties and by its EPR spectrum. The results unambiguously indicate that His-106 and His-421 are the ligands of the six-coordinate low spin cytochrome b563.5. Although the data are not definitive in making additional metal ligation assignments of the remaining four totally conserved histidines, a reasonable model is suggested for the structure of the catalytic core of the cytochrome o complex and, by extrapolation, of cytochrome c oxidase. PMID- 1309810 TI - Reducing inositol lipid hydrolysis, Ins(1,4,5)P3 receptor availability, or Ca2+ gradients lengthens the duration of the cell cycle in Xenopus laevis blastomeres. AB - We have microinjected a mAb specifically directed to phosphatidylinositol 4,5 bisphosphate (PIP2) into one blastomere of two-cell stage Xenopus laevis embryos. This antibody binds to endogenous PIP2 and reduces its rate of hydrolysis by phospholipase C. Antibody-injected blastomeres undergo partial or complete arrest of the cell cycle whereas the uninjected sister blastomeres divided normally. Since PIP2 hydrolysis normally produces diacylglycerol (DG) and inositol 1,4,5 triphosphate (Ins[1,4,5]P3), we attempted to measure changes in the levels of DG following stimulation of PIP2 hydrolysis in antibody-injected oocytes. The total amount of DG in antibody-injected oocytes was significantly reduced compared to that of water-injected ones following stimulation by either acetylcholine or progesterone indicating that the antibody does indeed suppress PIP2 hydrolysis. We also found that the PIP2 antibodies greatly reduced the amount of intracellular Ca2+ released in the egg cortex during egg activation. As an indirect test for Ins(1,4,5)P3 involvement in the cell cycle we injected heparin which competes with Ins(1,4,5)P3 for binding to its receptor, and thus inhibits Ins(1,4,5)P3-induced Ca2+ release. Microinjection of heparin into one blastomere of the two-cell stage embryo caused partial or complete arrest of the cell cycle depending upon the concentration of heparin injected. We further investigated the effect of reducing any [Ca2+]i gradients by microinjecting dibromo-BAPTA into the blastomere. Dibromo-BAPTA injection completely blocked mitotic cell division when a final concentration of 1.5 mM was used. These results suggest that PIP2 turnover as well as second messenger activity influence cell cycle duration during embryonic cell division in frogs. PMID- 1309811 TI - Cell-free fusion of endocytic vesicles is regulated by phosphorylation. AB - Okadaic acid and microcystin-LR, both potent inhibitors of protein phosphatases (PP), blocked vesicle fusion in a cell-free system. The effect of okadaic acid was reversed by the purified catalytic subunit of PP2A, but not PP1. Inhibition was gradual, required Mg-ATP, and was reduced by protein kinase inhibitors, indicating that it was mediated via protein phosphorylation. A candidate protein kinase would be cdc2 kinase, which normally is active in mitotic extracts and has been shown to inhibit endocytic vesicle fusion (Tuomikoski, T., M.-A. Felix, M. Doree, and J. Gruenberg. 1989. Nature (Lond.). 342:942-945). However, it would appear that cdc2 kinase is not responsible for inhibition by okadaic acid. When compared to cytosol prepared from mitotic cells, okadaic acid did not increase cdc2 kinase activity sufficiently to account for the inhibition. In addition, inhibition was maintained when cdc2 protein was depleted from cytosol. PMID- 1309812 TI - Genetic analysis of a Drosophila microtubule-associated protein. AB - The 205-kD microtubule-associated protein (205K MAP) is one of the principal MAPs in Drosophila. 205K MAP is similar to the HeLa 210K/MAP4 family of MAPs since it shares the following biochemical properties: it is present in several isoforms, has a molecular mass of approximately 200 kD, and is thermostable. Furthermore, immuno-crossreactivity has been observed between mouse MAP4, HeLa 210K, and Drosophila 205K MAP. Currently, there is little information concerning the biological function of this group of nonmotor MAPs. We have used a classical genetic approach to try to identify the role of the 205K MAP in Drosophila by isolating mutations in the 205K MAP gene. An F2 lethal screen was used to acquire deficiencies of 100EF, the chromosomal location of the 205K MAP gene. Drosophila bearing a homozygous deficiency for the 205K MAP region are fully viable and show no obvious phenotype. A recently developed polymerase chain reaction screen was also used to recover five P-element insertions upstream from the 205K MAP gene. Western blot analysis has shown that these insertions result in hypomorphic mutations of the 205K MAP gene. As was seen with animals that have no 205K MAP, these mutations appear to have no phenotype. These data unambiguously demonstrate that the 205K MAP gene is inessential for development. These results also suggest that there may exist protein(s) with redundant function that can substitute for 205K MAP. PMID- 1309813 TI - Phorbol ester induced osteoclast-like differentiation of a novel human leukemic cell line (FLG 29.1). AB - Studies on human osteoclast formation have been hampered by lack of a defined isolated progenitor cell population. We describe here the establishment of a human leukemic cell line (designated FLG 29.1) from bone marrow of a patient with acute monoblastic leukemia. The cultured cells are predominantly undifferentiated leukemic blasts, but addition of 12-o-tetradecanoylphorbol 13-acetate (TPA; 0.1 microM) induces irreversible differentiation into adherent, non-dividing, multinucleated cells. TPA-treated cells bear surface antigens typical of fetal osteoclasts, degrade 45Ca-labeled devitalized bone particles, display tartrate resistant acid phosphatase in both mononuclear and multinuclear cells and receptors for calcitonin. Calcitonin increases intracellular cAMP accumulation in TPA-treated cells. TPA-treated cells show some ultrastructural features of osteoclasts as evidenced by transmission EM. These results indicate that FLG 29.1 cells may represent an osteoclast committed cell population, which upon induction with TPA acquire some morphological, phenotypical, and functional features of differentiated osteoclasts. PMID- 1309814 TI - Compartmentalization of PDGF on extracellular binding sites dependent on exon-6 encoded sequences. AB - The PDGFs are a family of molecules assembled as disulfide-bonded homo- and heterodimers from two distinct but highly homologous polypeptide chains (PDGF-A and PDGF-B). Two PDGF A-chain transcripts, which arise from alternative usage of the 69-bp exon 6 and exon 7, give rise to two forms of PDGF-A. In spite of the conservation of two PDGF A-chain forms over at least 350 million years, no differences in their biological activities have been identified. We have investigated the activity of the sequence encoded by the alternatively spliced exon 6 of the PDGF A-chain (peptide AL). Addition of peptide AL at 10(-5)-10(-9) M to cultured endothelium and smooth muscle induced a dose-dependent, 3-20-fold increase in PDGF in conditioned media within 30 min. Peptide AL had no detectable effect on A- or B-chain transcript levels, and decrease in culture temperature did not prevent rapid release of PDGF. In human umbilical vein endothelial cells treated with peptide AL, the PDGF release was principally PDGF-BB, while in smooth muscle cells it was primarily PDGF-AA. The capacity to induce release of PDGF is shared by the homologous peptide encoded by exon 6 of the B-chain of PDGF. Binding studies and cross-linking analysis are consistent with a charge based association of exon 6 sequences with membrane- and matrix-associated heparan-sulfate proteoglycans. We hypothesize that translation of exon 6 of the A or B-chain of PDGF results in compartmentalization of these forms of PDGF with HS-PG, whereas forms lacking this sequence would be soluble and diffuse. PMID- 1309815 TI - A mutation in the signal recognition particle 7S RNA of the yeast Yarrowia lipolytica preferentially affects synthesis of the alkaline extracellular protease: in vivo evidence for translational arrest. AB - Replacement of the signal recognition particle (SRP) 7S gene (SCR1) on a replicating plasmid with scr1-1 (G to A at 129 and A to T at 131 in the consensus sequence -GNAR- in the loop of domain III) resulted in temperature sensitivity for growth of cells in which both chromosomal SRP 7S RNA genes were deleted. Pulse-chase immunoprecipitation experiments were done after a shift to non permissive temperature using the major secreted protein the alkaline extracellular protease (AEP) as a reporter molecule. No untranslocated AEP precursor was detected in a strain with scr1-1 on a plasmid, but the amount of the largest AEP precursor (55 kD) immunoprecipitated as a percentage of total protein synthesized was reduced 68% compared to an isogenic strain with SCR1 on the plasmid. The possibility that an untranslocated precursor was synthesized but not detected because of instability was largely eliminated by detection of a 53 kD untranslocated precursor of a mutated AEP (P17M; methionine replaced proline in the second position of the pro-peptide) which chased to the 55-kD translocated AEP precursor. Thus, SRP has a role in the biosynthesis of AEP. Possibly, the scr1-1 mutation does not affect signal recognition or translational arrest but instead results in maintenance of translational arrest of AEP synthesis. The results also suggest that AEP can be translocated in vivo either co translationally in which SRP is at least involved in biosynthesis or posttranslationally without SRP involvement. PMID- 1309816 TI - Activation of insulin-epidermal growth factor (EGF) receptor chimerae regulates EGF receptor binding affinity. AB - Cell surface tyrosine kinase receptors are subject to a rapid activation by their ligand, which is followed by secondary regulatory processes. The IHE2 cell line is a unique model system to study the regulation of EGF binding to EGF receptors after activation of the EGF receptor kinase. IHE2 cells express both a chimeric insulin-EGF receptor kinase (IER) and a kinase-deficient EGF receptor (HER K721A). We have previously reported that IER is an insulin-responsive EGF receptor tyrosine kinase that activates one or several serine/threonine kinases, which in turn phosphorylate(s) the unoccupied HER K721A. In this article we show that insulin through IER activation induces a decrease in 125I-EGF binding to IHE2 cells. Scatchard analysis indicates that, as for TPA, the effect of insulin can be accounted for by a loss of the high affinity binding of EGF to HER K721A. Since this receptor transmodulation persists in protein kinase C downregulated IHE2 cells, it is likely to be due to a mechanism independent of protein kinase C activation. Using an in vitro system of 125I-EGF binding to transmodulated IHE2 membranes, we illustrate that the inhibition of EGF binding induced by IER activation is related to the phosphorylation state of HER K721A. Further, studies with phosphatase 2A, or at a temperature (4 degrees C) where only IER is functional, strongly suggest that the loss of high affinity EGF binding is related to the serine/threonine phosphorylation of HER K721A after IER activation. Our results provide evidence for a "homologous desensitization" of EGF receptor binding after activation of the EGF receptor kinase of the IER receptor. PMID- 1309817 TI - Identification of the sea urchin egg receptor for sperm using an antiserum raised against a fragment of its extracellular domain. AB - Sea urchin egg fertilization requires the species-specific interaction of molecules on the sperm and egg surfaces. Previously, we isolated an extracellular, 70-kD glycosylated fragment of the S. purpuratus egg receptor for sperm by treating the eggs with lysylendoproteinase C (Foltz, K. R., and W. J. Lennarz. 1990. J. Cell Biol. 111:2951-2959). To characterize the receptor further, we have generated a polyclonal antiserum (anti-70KL) against the purified 70-kD fragment. Anti-70KL was found to react with a single polypeptide of approximately 350 kD on Western blots, presumed to be the intact receptor, in an egg cell surface preparation. This polypeptide appeared to be tightly associated with the plasma membrane/vitelline layer complex, as it was released from these preparations only by detergent treatment. Immunofluorescence microscopy revealed that the receptor was distributed evenly over the egg surface. The anti-70KL was species specific both in its ability to recognize the egg surface protein and to inhibit sperm binding. Fab fragments generated from affinity-purified anti-70KL also bound to the egg surface and inhibited sperm binding in a concentration-dependent manner. Interestingly, treatment with Fabs caused a small percentage of eggs to undergo cortical granule exocytosis, even in the absence of external Ca2+. These results confirm earlier findings indicating that the receptor is a cell surface glycoprotein of high molecular weight that species specifically binds sperm. This antiserum provides a powerful tool for further investigation of gamete interactions and the structure of the sperm receptor. PMID- 1309818 TI - Inositol phospholipid metabolism may trigger flagellar excision in Chlamydomonas reinhardtii. AB - Chlamydomonas reinhardtii cells shed their flagella in response to environmental stress. Under favorable conditions, flagella are quickly regrown. To learn more about the signals that trigger flagellar excision and regrowth we have investigated inositol phospholipid metabolites, molecules implicated in signal transduction in several other systems. After deflagellation by low pH or mastoparan, a potent activator of G proteins, there was a rapid increase in levels of inositol 1,4,5-trisphosphate measured by use of receptor-binding assays and HPLC. This increase was concomitant with a decrease in levels of phosphatidylinositol 4,5-bisphosphate and was followed by an increase in phosphatidic acid, results consistent with activation of phospholipase C and diacylglycerol kinase. Additional experiments suggest that this activated phospholipase C is not important for flagellar regrowth but plays a role in informing the excision apparatus of the environmental stress. Addition of neomycin (an inhibitor of phospholipase C) before exposure of cells to low pH or mastoparan prevented the increase in inositol 1,4,5-trisphosphate and also prevented deflagellation. Addition of neomycin after deflagellation blocked increases in inositol 1,4,5-trisphosphate that normally followed deflagellation, but did not block flagellar assembly. Furthermore, a flagellar excision-defective mutant, fa-1, did not shed its flagella in response to low pH or mastoparan, yet both of these agents activated phospholipase C in these cells. The results suggest that activation of phospholipase C, possibly via a G protein, is a proximal step in the signal transduction pathway inducing deflagellation in Chlamydomonas. PMID- 1309820 TI - Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor. AB - We recently isolated a cDNA clone encoding a functional platelet thrombin receptor that defined a unique mechanism of receptor activation. Thrombin cleaves its receptor's extracellular amino terminal extension, unmasking a new amino terminus that functions as a tethered peptide ligand and activates the receptor. A novel peptide mimicking this new amino terminus was a full agonist for platelet secretion and aggregation, suggesting that this unusual mechanism accounts for platelet activation by thrombin. Does this mechanism also mediate thrombin's assorted actions on non-platelet cells? We now report that the novel thrombin receptor agonist peptide reproduces thrombin-induced events (specifically, phosphoinositide hydrolysis and mitogenesis) in CCL-39 hamster lung fibroblasts, a naturally thrombin-responsive cell line. Moreover, these thrombin-induced events could be recapitulated in CV-1 cells, normally poorly responsive to thrombin, after transfection with human platelet thrombin receptor cDNA. Our data show that important thrombin-induced cellular events are mediated by the same unusual mechanism of receptor activation in both platelets and fibroblasts, very likely via the same or very similar receptors. PMID- 1309819 TI - Isoform-specific subcellular targeting of glucose transporters in mouse fibroblasts. AB - GLUT1, the erythrocyte glucose transporter, and GLUT4, the adipose/muscle transporter, were each expressed in NIH-3T3 cells by retrovirus-mediated gene transfer. In fibroblasts overexpressing GLUT1, basal as well as insulin stimulated deoxyglucose uptake was increased. Expression of GLUT4 was without affect on either basal or hormone stimulated hexose uptake. Localization of each of the transporters by indirect immunofluorescence revealed that, whereas GLUT1 was found primarily on the cell surface, GLUT4 was directed to vesicles in a perinuclear distribution and throughout the cytoplasm. The GLUT4-containing compartment represented neither Golgi complex nor lysosomes, as evidenced by the failure of lgp110 or Golgi mannosidase to co-localize. However, there was substantial overlap between the distribution of GLUT4 and the transferrin receptor, and some colocalization of the transporter isoform with the manose-6 phosphate receptor. In addition, when FITC-wheat germ agglutinin bound to the cell surface was allowed to internalize at 37 degrees C, it concentrated in vesicular structures coincident with GLUT4 immunoreactivity. These data establish that GLUT1 and GLUT4 contain within their amino acid sequences information which dictates targeting to distinct cellular compartments. Moreover, GLUT4 can be recognized by those cellular factors which direct membrane proteins to the endosomal pathway. PMID- 1309821 TI - Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells. AB - 5-hydroxytryptamine (5-HT) is a mitogen for fibroblasts, vascular smooth muscle cells, renal mesangial cells, and jejunal crypt cells. The human carcinoid cell line (termed BON) that we established in our laboratory from a pancreatic carcinoid tumor produces and secretes 5-HT. In this study, therefore, we examined the effect of 5-HT on growth of BON cells. Furthermore, by use of selective 5-HT receptor antagonists, we examined receptor and post-receptor mechanisms by which 5-HT-induced responses were produced. 5-HT stimulated growth of BON cells. 5-HT stimulated phosphatidylinositol (PI) hydrolysis in a dose-dependent fashion and inhibited cyclic AMP production in a dose-dependent fashion. The 5-HT1A/1B receptor antagonist, SDZ 21-009, prevented the reduction of cyclic AMP production evoked by 5-HT and inhibited the mitogenic action of 5-HT. The 5-HT1C/2 receptor antagonist, mesulergine, competitively inhibited PI hydrolysis, but did not affect the mitogenic action of 5-HT. The mitogenic action of 5-HT and the reduction of cyclic AMP production evoked by 5-HT were also inhibited by pertussis toxin. These results suggest that 5-HT is an autocrine growth factor for BON cells and that mitogenic mechanism of 5-HT involves receptor-mediated inhibition of the production of cyclic AMP which may be linked to pertussis toxin sensitive GTP binding protein. 8-bromo-cyclic AMP inhibited growth of BON cells whereas 8-bromo-cyclic GMP had no effect on cell growth. Involvement of protein kinase A in BON cell growth regulation was confirmed by the observation that a cAMP-dependent protein kinase antagonist (Rp-cAMPS) could stimulate BON cell growth. PMID- 1309822 TI - Low intracellular pH induces redistribution of fodrin and instabilization of lateral walls in MDCK cells. AB - We have studied the effect of intracellular pH on the establishment and maintenance of the cellular polarity in MDCK cells by utilizing nigericin which causes lowering of the cytoplasmic pH. At pH below 6.5, MDCK cells lost their polarized morphology and became roundish, with an increased apical area and shortened and unstable lateral walls. The lateral wall marker proteins uvomorulin and Na,K-ATPase remained segregated to the lateral walls in the acidified cells, as shown by immunofluorescence microscopy. Fodrin, on the other hand, was released from its normal basolateral residence and was found in the cytoplasm. Actin, which normally co-localizes with fodrin along the basolateral walls, showed a dotty distribution in the cytoplasm of acidified cells, while stress fibers remained intact. Microtubular network appeared flattened, but the Golgi complex retained its apical position. The pH change-induced alterations were readily reversible, as the normal basal-apical polarity (columnar shape, distinct apical and lateral domains with apposing and stiff lateral membranes) was reformed within 10 minutes after restoring the normal pH gradient across the cell membrane. This coincided with the translocation of fodrin from the cytoplasm to the lateral walls. The results show that lowering of intracellular pH leads to temporary segregation of fodrin from the other components of the membrane skeleton assembly, and that association of fodrin with the lateral walls seems to be a prerequisite for their close apposition and for the maintenance of normal basal-axial polarity. PMID- 1309823 TI - Early increase in lymphocyte cyclic nucleotide phosphodiesterase activity upon mitogenic activation of human peripheral blood mononuclear cells. AB - Cyclic nucleotide phosphodiesterase activity of human peripheral blood mononuclear cells was significantly increased following a short (30 min) incubation with the mitogenic lectin Concanavalin A. Con A stimulated phosphodiesterase activity to the same extent whatever the subcellular compartment (homogenate, cytosol or pellet). Further separation of the Con A activated mononuclear cells into lymphocyte-enriched and monocyte-enriched populations showed that the Con A-induced increase of phosphodiesterase activity exclusively affected the lymphocyte-enriched population. In lymphocytes, cyclic GMP phosphodiesterase activity was more importantly enhanced by Con A (+275%) than cyclic AMP phosphodiesterase activity (+75%). The increase of both activities occurred as early as from 10 min of Con A incubation and proved to be maximal with Con A doses of 2.5 and 5 micrograms per 10(6) cells, lower and higher doses being less effective. Inhibition experiments with reference inhibitors suggested that, among the high affinity phosphodiesterase isoforms, the cyclic GMP-inhibited enzyme might be more selectively enhanced by Con A than the cyclic AMP-specific, Rolipram-sensitive one. The non-mitogenic lectin Helix pomatia hemagglutinin, was not able to enhance cyclic nucleotide phosphodiesterase activity of human mononuclear cells whereas anti-CD3 monoclonal antibody, although being less effective than Con A, exhibited a significant stimulatory effect. Putting together these results suggest that the early increase in phosphodiesterase activity might be a normal step involved in the mitogenic activation of human lymphocyte. PMID- 1309824 TI - SV40-immortalization of rabbit articular chondrocytes: alteration of differentiated functions. AB - Cell lines were established from rabbit articular chondrocytes following transfection with a plasmid encoding SV40 early function genes. This resulted in cell immortalization (130 passages have been completed for the oldest cell line) with acquisition of characteristics of partial transformation such as reduced serum requirements for normal and clonal growth. The immortalized chondrocytes, called SVRAC, did not form multilayer foci when maintained in postconfluent culture. Their ability to form colonies in soft agar was not increased in comparison with normal chondrocytes, but they were weakly tumorigenic in nude mice. SVRAC lost the ability to synthesize type II collagen and Alcian blue stainable matrix, which are markers of the differentiated chondrocyte phenotype, and synthesized predominantly type I collagen. Studies of collagen gene expression showed that pro alpha 1 (II) mRNA was undetectable, whereas pro alpha 1 (I) collagen mRNA was expressed even in late passage cultures. Unlike normal dedifferentiated chondrocytes, SVRAC were unable to re-express the differentiated phenotype in response to tridimensional culture or microfilament depolymerization. Cell lines obtained from chondrocytes transfected either in primary culture or just after release of cells from cartilage displayed the same behaviour. Thus SV40 early genes were able to immortalize rabbit articular chondrocytes, but the resulting cell lines displayed an apparently irreversibly dedifferentiated phenotype. These cell lines can be used as models to identify regulatory pathways that are required for the maintenance or reexpression of differentiated function in chondrocytes. PMID- 1309825 TI - Karyotypic and phenotypic changes during in vitro aging of human endothelial cells. AB - Karyotypic and phenotypic changes were found in human adult endothelial cells (EC) during aging in vitro. A trisomy of chromosome 11 was found in 11 out of 12 EC cultures examined, derived from 9 cell lines from 8 donors. The incidence of this trisomy in some cell lines increased over time from 0% to as much as 100% near the end of their in vitro life span. A number of oncogenes and other important genes are on chromosome 11. These genes might play a role in the changes observed. An increase in the percentage of polyploid cells was also found near the end of the in vitro life span in 6 lines. The cellular levels of two gene products characteristic of the EC, von Willebrand factor (vWF) or Factor VIII, and angiotensin converting enzyme (ACE) were also monitored. vWf was studied in 2 lines and was decreased in both with serial passage. ACE decreased in three out of the four lines examined. These chromosomal and phenotypic changes which occur with increasing age in vitro make the endothelial cell a suitable model to study in vitro culture-related changes, senescence, cardiovascular disease, and tumorigenesis. PMID- 1309826 TI - Dibutyryl-cAMP increases functions of 5-hydroxytryptamine2 receptors, but not of beta 2-adrenergic receptors, in a clonal cell line of rat neurotumor RT4. AB - A peripheral nervous system cell line RT4-B, established by Imada and Sueoka (Dev. Biol., 66:97-108, 1978), was shown to respond to serotonin [5 hydroxytryptamine (5-HT)] and catecholamines. 5-HT induced a small and transient increase in cytosolic free Ca2+ concentration ([Ca2+]i) in the RT4-B cells. The increase was effectively blocked by 5-HT2 receptor antagonists (spiperone, ritanserin and mianserin), but not by a 5-HT3 receptor antagonist (MDL72222), or a alpha 1-adrenergic receptor antagonist (prazosin), indicating that RT4-B cells express 5-HT2 receptors. On the other hand, catecholamines increased cyclic AMP production by RT4-B. The order of potency for stimulating cyclic AMP synthesis was isoproterenol greater than epinephrine much greater than norepinephrine much greater than dopamine, and the stimulation was effectively inhibited by the nonselective beta-adrenergic receptor antagonist propranolol, but not by the beta 1-adrenergic receptor antagonist atenolol, suggesting that RT4-B cells express beta 2-adrenergic receptors. The differentiating agent N6,2'-O-dibutyryladenosine 3',5'-monophosphate (dibutyryl-cAMP) enhanced the 5-HT-induced [Ca2+]i increase, but not the catecholamine-induced cyclic AMP production. The increase in the 5-HT response paralleled the increase in the density of 5-HT2 receptors. n-Butyric acid (2 mM) and 8-bromoadenosine 3',5'-monophosphate (1 mM) also increased the 5 HT response, and the sum of these increases was nearly equal to that induced by dibutyryl-cAMP. These results indicate that RT4-B is a novel model cell line for the study of 5-HT2 and beta 2-adrenergic receptors and their second messenger responses and for the analysis of the mechanisms how 5-HT2 receptor gene expression is controlled. PMID- 1309827 TI - Differential regulation of cerebroside sulfotransferase and 2',3'-cyclic nucleotide 3'-phosphodiesterase by basic fibroblast growth factor in relation to proliferation in rat oligodendrocyte cultures. AB - Previous results (Fressinaud, C., Sarlieve, L.L., and Labourdette, G. J. J. Cell. Physiol., 141:667-674, 1989b) have shown that cerebroside sulfotransferase (CST; EC 2.8.2.11) is enriched in pure rat oligodendrocyte (OL) cultures and that its activity is increased by factors mitogenic for OL precursors and galactocerebroside (GC) expressing OL, such as basic fibroblast growth factor (bFGF), platelet-derived growth factor, and high insulin concentrations. In contrast, transforming growth factor beta or low insulin concentrations were found to be ineffective in this culture system. As bFGF mainly enhanced the proliferation of OL precursors (GC negative cells) rather than that of differentiated (GC+) cells, a relationship between OL precursor proliferation and CST increase was suggested. This hypothesis was first tested in 20-day-old OL cultures grown in chemically defined medium. The dose-response curve of [125I] Iododeoxyuridine ([125I]dUrd) incorporation toward bFGF was parallel to that of CST specific activity, and maximal stimulation was reached at 5 ng/ml bFGF for both. In contrast, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP; EC 3.1.4.37) specific activity decreased after bFGF treatment. To determine if CST increase was linked to the proliferation of OL precursors induced by bFGF, cell proliferation was blocked by cytosine arabinoside (ARA-C). From 10(-8) to 10(-5) M ARA-C there was a dose-dependent inhibition of cell proliferation and a decrease in CST specific activity, whereas CNP specific activity was enhanced. When the cells were treated with bFGF and 10(-6) M ARA-C together, the proliferation was completely blocked and CST activity decreased by 72% below control values, whereas CNP activity was not significantly decreased. Immunocytochemical studies showed that the number of sulfatide-expressing cells and the number of cycling cells were increased after bFGF treatment, but that there was no overlapping between these two populations. Taken together these results suggest that CST activity and sulfatide expression appear shortly after the arrest of OL precursor division. PMID- 1309828 TI - Thrombin inhibits proliferation of the human megakaryoblastic MEG-01 cell line: a possible involvement of a cyclic-AMP dependent mechanism. AB - Thrombin, a potent platelet activating agent, has previously been found to increase intracellular calcium levels and/or thromboxane A2 synthesis in leukemic cell lines exhibiting specific markers of the megakaryocyte/platelet lineage. However, its functional role on these cells has not been defined. As thrombin is implicated in the regulation of cellular proliferation or differentiation in various other cell types, we investigated the functional effects of thrombin on the megakaryoblastic MEG-01 cell line, and further explored its receptor coupling mechanisms on these cells. We observed that thrombin caused in 1% serum containing culture medium, a reduction in the proliferation of MEG-01 cells, without affecting their differentiation stage as determined by the expression of platelet glycoproteins GPIIb/IIIa and GPIb, FVIII-related-antigen and cell-size measurement, which are specific markers for megakaryocyte maturation. In addition, incubation of MEG-01 cells with thrombin resulted in dose-dependent increases in cAMP levels, and in inositol-trisphosphate formation and intracellular Ca2+ levels. All these responses required thrombin proteolytic activity. The lipoxygenase inhibitor, nordihydroguaiaretic acid, blunted thrombin induced calcium increase without affecting thrombin-induced increase in cAMP levels, suggesting different thrombin coupling mechanisms with these two second messenger pathways. In addition, the inhibitory effect of thrombin on MEG-01 cell growth was mimicked by cAMP level enhancing agents such as forskolin, prostaglandin E1 and Bt2cAMP. These results suggest the involvement of a cAMP dependent mechanism in the thrombin-induced reduction in MEG-01 cell growth. PMID- 1309829 TI - Evidence for receptor-mediated calcium entry and refilling of intracellular calcium stores in FRTL-5 rat thyroid cells. AB - The aim of the present study was to investigate the relationship between agonist induced changes in intracellular free Ca2+ ([Ca2+]i) and the refilling of intracellular Ca2+ stores in Fura 2-loaded thyroid FRTL-5 cells. Stimulating the cells with ATP induced a dose-dependent increase in ([Ca2+]i). The ATP-induced increase in [Ca2+]i was dependent on both release of sequestered intracellular Ca2+ as well as influx of extracellular Ca2+. Addition of Ni2+ prior to ATP blunted the component of the ATP-induced increase in [Ca2+]i dependent on influx of Ca2+. In cells stimulated with ATP in a Ca(2+)-free buffer, readdition of Ca2+ induced a rapid increase in [Ca2+]i; this increase was inhibited by Ni2+. In addition, the ATP-induced influx of 45Ca2+ was blocked by Ni2+. Stimulating the cells with noradrenaline (NA) also induced release of sequestered Ca2+ and an influx of extracellular Ca2+. When cells were stimulated first with NA, a subsequent addition of ATP induced a blunted increase in [Ca2+]i. If the action of NA was terminated by addition of prazosin, and ATP was then added, the increase in [Ca2+]i was restored to control levels. Addition of Ni2+ prior to prazosin inhibited the restoration of the ATP response. In the presence of extracellular Mn2+, ATP stimulated quenching of Fura 2 fluorescence. The quenching was probably due to influx of Mn2+, as it was blocked by Ni2+. The results thus suggested that stimulating release of sequestered Ca2+ in FRTL-5 cells was followed by influx of extracellular Ca2+ and rapid refilling of intracellular Ca2+ stores. PMID- 1309830 TI - A mediastinal mass in a red-faced young woman. PMID- 1309831 TI - Premature pubarche: etiological heterogeneity. AB - Premature pubarche is characterized by pubic hair, adult type body odor, acne, and axillary hair before 8 yr of age in girls and 9.5 yr of age in boys. Causes of this premature virilization include premature adrenarche, mild errors of steroidogenesis, precocious puberty, and adrenal and gonadal tumors. To determine whether any clinical parameters are helpful in distinguishing which children should undergo further evaluation for mild congenital adrenal hyperplasia, we performed ACTH stimulation tests in 69 children with premature pubarche and 8 pubertal controls. Patients were categorized as having typical (pubic hair with or without axillary hair and body odor) or atypical (pubic hair and genital enlargement) premature pubarche. Blood samples, before and 30 min after iv bolus administration of synthetic ACTH, were obtained for progesterone, 17 hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 11-deoxycortisol, and cortisol measurements. The patients were divided into 4 groups based on their individual responses to ACTH stimulation: premature adrenarche (no apparent defect in steroidogenesis), possible decreased 21-hydroxylase activity, possible decreased 3 beta-hydroxysteroid dehydrogenase activity, and indeterminate responses. Five of 11 (45%) children with atypical premature pubarche and 7 of 58 (12%) children with typical premature pubarche were found to have evidence of mild defects in steroidogenesis. Similar to previous reports in postpubertal women, only responses to ACTH stimulation allowed accurate classification of these patients. PMID- 1309833 TI - Cortisol receptor resistance: the variability of its clinical presentation and response to treatment. AB - Primary (partial) cortisol receptor resistance was previously reported in a total of 7 patients and 14 asymptomatic family members. Its occurrence is considered to be extremely rare. In the present study we report on 6 patients (2 males and 4 females) with the syndrome. The first male patient presented with mild hypertension. Hydrochlorothiazide therapy resulted in life-threatening hypokalemia. The second male patient had slight hypertension without hypokalemia. All four female patients presented between the age of 20-30 yr with acne, hirsutism, and irregular menstruations. Low dose dexamethasone therapy (1-1.5 mg/day) was of clinical benefit in these patients. All patients showed insufficient suppression of serum cortisol concentrations in the overnight 1-mg dexamethasone test. The diurnal rhythm of ACTH and cortisol was intact, albeit at an elevated level. There was a normal increase in ACTH, cortisol, and GH (except in one obese patient) in response to insulin-induced hypoglycemia, while cortisol production was elevated in three patients. Circulating adrenal androgen levels were increased in all patients. Glucocorticoid receptors were investigated in a whole cell dexamethasone binding assay in mononuclear leukocytes. In the first male patient, the number of receptors was very low, while the affinity was lower than that in controls. A lowered affinity to dexamethasone was found in one female patient, while a lowered number of receptors was found in three patients. In the second male patient, no abnormalities were found. As a bioassay for glucocorticoid action we also measured dexamethasone suppressibility of mitogen stimulated incorporation of [3H]thymidine in mononuclear leukocytes. In the male patient with normal receptor status, dexamethasone suppressibility of [3H]thymidine incorporation was significantly lower than that in healthy controls with respect to both maximal suppression and IC50. Partial cortisol receptor resistance might be less rare than previously thought. In the six patients presented, at least three different forms can be recognized. Therapy with dexamethasone was successful in female patients with acne and hirsutism, as the secondary increase in the production of adrenal androgens was effectively controlled. PMID- 1309832 TI - The role of adrenocorticotropin testing in evaluating girls with premature adrenarche and hirsutism/oligomenorrhea. AB - To identify biochemical predictors for future development of hirsutism and/or oligomenorrhea (H/O) in girls with premature adrenarche (PA), we performed dexamethasone-suppressed ACTH stimulation tests in girls with PA (n = 46), young women (n = 44) with H/O, and adult women (n = 31). Cortisol, androstenedione, dehydroepiandrosterone, and 17-hydroxyprogesterone were measured. Seven girls with PA (15%) and seven with H/O (16%) had evidence of nonclassical adrenal steroid biosynthetic defects [nonclassical congenital adrenal hyperplasia (NCAH)]. Twenty-five girls with PA (54%) and 28 girls with H/O (64%) had the moderately elevated 17-hydroxyprogesterone response to ACTH that has been reported in obligate heterozygotes for 21-hydroxylase deficiency. There were no clinical features that distinguished the girls with NCAH from the others. ACTH testing is an important tool in distinguishing those girls with PA and H/O who have NCAH. Although we could find no differences in other adrenal steroid hormones that might predict which of the other girls with PA might late develop H/O, black girls comprised a substantially smaller fraction of the population with H/O than of the population with PA (2% vs. 26%; chi 2 = 8.5; P less than 0.005). This observation suggests that PA, in blacks who do not have NCAH, is more likely to be a benign condition/than in other ethnic groups. PMID- 1309834 TI - Hair growth effects of oral administration of finasteride, a steroid 5 alpha reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque. AB - A 5 alpha-reductase inhibitor, finasteride, was administered orally at 0.5 mg/day, alone or in combination with topical 2% minoxidil, for 20 weeks to determine the effects on scalp hair growth in balding adult male stumptail macaque monkeys. A 7-day dose-finding study showed that both 0.5- and 2.0-mg doses of the drug produced a similar diminution in serum dihydrotestosterone (DHT) in male stumptails. Hair growth was evaluated by shaving and weighing scalp hair at baseline and at 4-week intervals during treatment to obtain cumulative delta hair weight (sum of the 4-week changes in hair weight from baseline) for the 20-week study. The activity of the 5 alpha-reductase enzyme was assessed by RIA of serum testosterone (T) and DHT at 4-week intervals. The combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Finasteride increased hair weight in four of five monkeys. When the data of the one nonresponsive monkey were excluded, finasteride elicited a significant elevation in hair weight compared to topical vehicle alone. Minoxidil also evoked a significant increase in hair weight compared to vehicle alone. Serum T was unchanged, whereas serum DHT was significantly depressed in monkeys that received either finasteride or the combination of finasteride and minoxidil. These data suggest that inhibition of the conversion of T to DHT by this 5 alpha-reductase inhibitor reverses the balding process and enhances hair regrowth by topical minoxidil in the male balding stumptail macaque. PMID- 1309835 TI - Sex steroid modulation of neurohypophysial hormone receptors in human nonpregnant myometrium. AB - Neurohypophysial hormone receptors were studied in myometrial specimens obtained from nonpregnant women using binding and in vitro contractility studies. The mathematical modeling of self- and cross-competition curves among [3H]oxytocin (OT), [3H]arginine vasopressin, the V1 vasopressin (VP) antagonist [3H]d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and the OT agonist [Thr4, Gly7] OT strongly indicates the presence of multiple classes of OT and arginine vasopressin receptors. The latter show the same pharmacological characteristics as the neurohypophysial hormone receptors described by our group for the human pregnant myometrium; in addition, they regulate the contractility of uterine strips. Blocking experiments were performed to evaluate the relative OT and V1 VP receptor distribution in 30 uterine specimens obtained from normal cycling and postmenopausal women. The glucuronoconjugate metabolites of 17 beta estradiol and progesterone were also measured in 16 patients in early morning urine samples taken the same day as surgery. Our results show that V1 VP receptors are not only present but also biologically active in all the uterine specimens studied with virtually equal density in normal cycling and postmenopausal women. However, their concentrations do not correlate with either estrogen or progesterone urinary levels. The lowest OT receptor density was found at mid-cycle and in menopause, independently of any correlation with the urinary estrogens. Conversely, OT receptors rise sharply in the late luteal phase and during menstruation. In addition they show a positive relationship with glucuronoconjugate metabolites of progesterone levels. These results indicate that progesterone does not inhibit the expression of uterine OT receptors in the human uterus. Furthermore, they imply that neurohypophysial hormones are involved in the control of uterine activity during the menstrual cycle. PMID- 1309836 TI - Effects of carbamazepine on pituitary-adrenal function in healthy volunteers. AB - Carbamazepine (CBZ) is a widely used therapeutic agent in seizure, pain, and mood disorders. Although CBZ has been shown to inhibit hypothalamic CRH secretion in vitro, limited data suggest that systemic CBZ induces pituitary-adrenal activation. Few data are available to reconcile these effects or clarify their mechanism(s), particularly in healthy human subjects. We report here a study of basal ACTH and cortisol secretion and their responses to ovine CRH administration in nine healthy volunteers, studied both during repeated (2-3 weeks) administration of CBZ and while medication free. CBZ significantly increased mean 24-h urinary free cortisol (mean +/- SE, 197 +/- 17 vs. 137 +/- 24 nmol/day; P less than 0.02) and evening basal total plasma cortisol (113 +/- 17 vs. 83 +/- 14 nmol/L; P less than 0.05) as well as cortisol-binding globulin-binding capacity (497 +/- 36 vs. 433 +/- 28 nmol/L; P less than 0.01). Despite the CBZ-induced hypercortisolism, plasma ACTH responses to CRH during CBZ treatment remained robust, rather than being suppressed by basal hypercortisolism. In fact, during CBZ treatment, we noted a positive correlation between the increase in basal plasma cortisol and the increase in the plasma ACTH response to CRH (r = 0.65; P less than 0.05). We also observed a reduction in cortisol-binding globulin binding capacity after CRH administration (315 +/- 25 vs. 433 +/- 28 nmol/L; P less than 0.001), which was accentuated by CBZ treatment (342 +/- 19 vs. 497 +/- 36 nmol/L; P less than 0.001; magnitude of fall, -155 +/- 22 nmol/L on CBZ vs. 118 +/- 11 nmol/L off CBZ; P less than 0.05). We conclude that CBZ increases plasma cortisol secretion in healthy volunteers independent of its effect on plasma cortisol-binding capacity. This pituitary-adrenal activation seems to reflect a pituitary, rather than a hypothalamic, effect of CBZ. Hence, despite CBZ-induced hypercortisolism, the ACTH response to CRH remained robust in direct proportion to the CBZ-induced rise in basal plasma cortisol. Thus, we propose that the increased cortisol secretion observed during CBZ treatment reflects a relative inefficacy of glucocorticoid negative feedback at the pituitary. This pituitary-driven increase in cortisol secretion combined with the expected reduction in centrally directed CRH secretion could contribute to the anticonvulsant properties of CBZ. PMID- 1309837 TI - Effects of conjugated estrogen on the calcitriol response to parathyroid hormone in postmenopausal women. AB - We evaluated the effects of estrogen on the calcitriol response to the active peptide, human PTH(1-34), in postmenopausal women. Fifteen women were studied before and again after at least 1 month of treatment with conjugated equine estrogens, 1.25 mg/day. Six women received two series of four graded peptide infusions, each with the sequence 200, 400, 800, and 1600 USP U hPTH(1-34). Nine women received only one dose of peptide, either 200 or 800 U, before and while taking estrogen. Baseline values and the incremental and percent changes in circulating calcitriol 24 h after the 20-min infusions were evaluated. Estrogen treatment resulted in significant reductions in blood levels of calcium (2.26 +/- 0.03 mmol/L vs. 2.16 +/- 0.02, P less than 0.05) and phosphorus (1.23 +/- .05 mmol/L vs. 1.14 +/- 0.03, P less than 0.005), a rise in serum calcitriol concentrations (42.2 +/- 3.9 pg/mL vs. 28.6 +/- 3.1, P less than 0.005), and no change in circulating PTH. The rise in calcitriol after 200 U hPTH(1-34) was significantly greater on estrogen (17.6 +/- 2.0 pg/mL vs. 9.5 +/- 1.8, P less than 0.01), but estrogen did not alter incremental responses to larger doses. When results were normalized for differences in baseline values, the estrogen related change in response to 200 U was no longer significant. hPTH(1-34) acutely increased urinary clearance of cAMP and phosphorus, but estrogen did not affect this response. We conclude that exogenous estrogen does not increase renal sensitivity to PTH in postmenopausal women. PMID- 1309838 TI - Expression of the genes encoding the insulin-like growth factors and their receptors in the human ovary. AB - Insulin-like growth factor-I (IGF-I) and IGF-II have been proposed as potential regulators of ovarian function. To gain further insight as to the possible role(s) of the IGFs in human ovarian physiology, we have characterized the expression of the genes encoding the IGFs and their corresponding receptors in the human ovary using solution hybridization/RNase protection assays. IGF-I gene expression was evident in liver, placenta, and whole premenopausal ovary, but not in luteinized granulosa cells. Use of 3'- and 5'-specific antisense RNA probes revealed the presence of IGF-I mRNAs encoding both the Ea and Eb forms of the E peptide as well as potential 5'-untranslated region splicing variants in liver, placenta, and whole menopausal ovary. Immunohistochemical studies localized the IGF-I peptide to the thecal-interstitial compartment. IGF-II mRNA transcribed from the fetal or fetal-neonatal IGF-II promoter was found in whole premenopausal ovary, luteinized granulosa cells, and placenta. Insulin and type I and type II IGF receptor mRNAs were detected in all tissues examined. Two protected probe fragments were seen with the type I IGF receptor probe in each case, suggesting the possibility of alternate splicing. These studies provide further evidence for a role of these growth factors in human ovarian function. PMID- 1309839 TI - Human decidua is a target tissue for bradykinin and kallikrein: phosphoinositide hydrolysis accompanies arachidonic acid release in uterine decidua cells in vitro. AB - The endocrine and intracellular mechanisms regulating prostaglandin precursor release in the uterine decidua during labor are unknown. This in vitro study investigates a potential role for a kallikrein-kinin system in the activation of phospholipid hydrolysis and arachidonic acid release in human decidua cells. Primary cultures of human decidua cells were prelabeled with [3H]inositol or [14C]arachidonic acid to monitor phosphoinositide hydrolysis and prostaglandin precursor release, respectively. Bradykinin (100 nmol/L) stimulated a rapid release of arachidonic acid (within 2 min) associated with an increase in inositol trisphosphate which was detectable after 20 s. Protein kinase C activation by phorbol ester enhanced arachidonic acid release in response to both bradykinin and the Ca++ ionophore A23187 but inhibited bradykinin-stimulated phosphoinositide hydrolysis. Epidermal growth factor also enhanced arachidonate release in response to both bradykinin and A23187. Kallikrein stimulated both phosphoinositide hydrolysis and arachidonic acid release in decidua cells. Kallikrein action was inhibited by the kallikrein protease inhibitor aprotinin and D-Arg[Hyp3Thi5,8,D-Phe7] bradykinin, a B2 receptor antagonist. Bradykinin also stimulated prostaglandin F2 alpha production in both primary decidua cell cultures and fibroblasts in the presence of interleukin-1 beta. These findings are consistent with a mediatory role for bradykinin in the action of kallikrein on decidua cells and suggest that inositol phospholipid hydrolysis is instrumental for arachidonic acid release in response to bradykinin in these cells. This study supports a novel role for a kallikrein-kinin system in the human uterine decidua. PMID- 1309840 TI - Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season. AB - The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure. PMID- 1309841 TI - Proinflammatory cytokines tumor necrosis factor-alpha and IL-6, but not IL-1, down-regulate the osteocalcin gene promoter. AB - A proinflammatory cytokine cascade, including IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and IL-8, is activated in response to infection or immunologic insult. Besides their immunologic effects, several of these mediators stimulate bone resorption and inhibit bone formation. Osteocalcin, the most abundant noncollagenous protein present in bone, is an osteoblast-specific product whose production closely correlates with bone formation, and which has also been implicated in control of bone resorption. IL-1 and TNF have previously been shown to down-regulate osteocalcin production in vitro and in vivo, although the mechanism of this inhibition is unknown. In the present studies, IL-1 beta and TNF-alpha both inhibited 1,25-dihydroxyvitamin D3-stimulated production of osteocalcin protein and mRNA by ROS 17/2.8 osteosarcoma cells, whereas IL-6 had no effect on protein and only weakly inhibited mRNA. To determine if down regulation was exerted at the transcriptional level, an osteocalcin promoter chloramphenicol acetyltransferase (CAT) fusion gene was constructed (PHOC-CAT). After transient transfection of PHOC-CAT into ROS 17/2.8 osteosarcoma cells, reporter CAT activity was up-regulated by vitamin D at concentrations above 10( 12) M. In screening studies, TNF-alpha (-57%) and IL-6 (-37%) inhibited vitamin D stimulated osteocalcin transcription, whereas IL-1 alpha, IL-1 beta, and IL-8 had no effect. Other immune cytokines and growth factors, including IL-2, IL-3, IL-7, and M-CSF, also failed to regulate osteocalcin transcription. Despite their lack of promoter regulation, IL-1 alpha and IL-1 beta also stimulated PGE2 production by ROS 17/2.8, further confirming the ability of the host cell to respond to these mediators. In dose-response experiments, down-regulation by TNF-alpha was significant at concentrations as low as 0.14 pM (0.1 U/ml), whereas approximately 10(4)-fold higher concentration of IL-6 was required to exert a similar effect. TNF-alpha-mediated down-regulation was unaffected by indomethacin. These data demonstrate that of these cytokines, TNF-alpha alone potently down-regulates osteocalcin promoter function, whereas IL-1 acts post-transcriptionally, possibly by reducing mRNA stability. Heterogeneity therefore exists among the proinflammatory cytokines with respect to the level at which control of osteocalcin expression is exerted. PMID- 1309842 TI - Secretory granule mediator release and generation of oxidative metabolites of arachidonic acid via Fc-IgG receptor bridging in mouse mast cells. AB - The releases of beta-hexosaminidase, LTC4, LTB4, and PGD2 after the bridging of Fc gamma R3 were assessed in mouse IL-3-dependent bone marrow-derived progenitor mast cells (BMMC), BMMC maintained in coculture with 3T3 fibroblasts separated by a filter to achieve maturation of the granules toward those of a serosal mast cell (SMC), and SMC that are the prototype of a mouse connective tissue mast cell. Bridging of Fc gamma R on BMMC with the 2.4G2 rat anti-Fc gamma RII/III mAb and anti-rat IgG elicited only 4% net release of beta-hexosaminidase and 4, 2, and 1 ng/10(6) cells of immunoreactive LTC4, LTB4, and PGD2, respectively. Bridging of Fc-IgE receptors (Fc epsilon R) on BMMC yielded 35% net release of beta-hexosaminidase and 9, 4, and 3 ng/10(6) cells of immunoreactive LTC4, LTB4, and PGD2, respectively. BMMC maintained in coculture responded to the bridging of Fc gamma R with statistically significant increases in the net percent release of beta-hexosaminidase to 16% and in the generation of immunoreactive LTC4 to 11 ng/10(6) cells, but without a significant change in the production of either LTB4 or PGD2. Bridging of Fc epsilon R on cocultured mast cells yielded a net percent release of beta-hexosaminidase and lipid mediator amounts and profile similar to those for BMMC. Bridging of Fc gamma R on purified mouse SMC resulted in a maximal net percent release of beta-hexosaminidase of 10% and the generation of 4, 1, and 17 ng/10(6) cells of immunoreactive LTC4, LTB4, and PGD2, respectively; the net percent release of beta-hexosaminidase and PGD2 generation were significantly greater than those obtained from BMMC. The Fc epsilon R-mediated net percent release of beta-hexosaminidase from purified SMC was 34%, with PGD2 being the predominant metabolite of arachidonic acid. That the predominant lipid mediator generated with activation by either Fc gamma R or Fc epsilon R is LTC4 for cocultured mast cells and PGD2 for SMC suggests that the mast cell phenotype rather than the receptor class being bridged determines the lipid mediator profile. The responsiveness to Fc gamma R bridging elicited by coculture of BMMC with fibroblasts in vitro and present in SMC derived in vivo relative to BMMC may relate to the previously measured increases in receptor number per cell, but may also involve the acquisition of an enhanced signal transduction capability, possibly through the increased expression of Fc gamma RIII. PMID- 1309843 TI - Virus-induced loss of class I MHC antigens from the surface of cells infected with myxoma virus and malignant rabbit fibroma virus. AB - Shope fibroma virus (SFV) is a leporipoxvirus that causes localized benign fibromas in immunocompetent adult rabbits that spontaneously regress due, in part, to a cell-mediated immune response. Myxoma virus (MYX) and malignant rabbit fibroma virus (MRV) are related leporipoxviruses that induce rapidly lethal generalized infections accompanied by tumors and immunosuppression. Because only these latter two viruses are known to compromise cell-mediated antiviral responses, cell surface levels of class I MHC molecules in SFV-, MRV-, and MYX infected cells were investigated by fluorescent activated cell sorting analysis using a variety of different anti-HLA mAb. After infection with MYX or MRV there is a rapid decrease in the levels of detectable surface class I epitopes as detected by each antibody and by 24 h postinfection class I MHC Ag levels at the cell surface approach the level of background fluorescence observed with control antibodies. In contrast, only a moderate class I decrease is seen during infection with either SFV or vaccinia virus, an orthopoxvirus that is neither tumorigenic nor immunosuppressive. Surface class I marker loss induced by MYX and MRV is not simply due to nonspecific inhibition of total cellular protein synthesis by the viruses because class I levels decrease much further than the extent measured by estimating surface marker turnover in the presence of the protein synthesis inhibitor cycloheximide. Thus the loss of cellular surface class I molecules greatly exceeds the drop in level caused by complete blockage of host cell gene expression, and must involve removal or masking of preexisting class I epitopes from the cell surface by MRV/MYX. Cell surface levels of the transferrin receptor are unaffected by MYX and MRV infection, suggesting the observed class I decrease is not a nonspecific effect on total cell surface glycoproteins. Analysis of cells infected with MRV/MYX in the presence of cycloheximide or of cytosine arabinoside, an inhibitor of poxviral DNA replication, indicates that the class I marker loss is mediated in part by one or more viral late gene products. A probable explanation is that MRV/MYX late protein(s) interact with the class I MHC complex to either physically sequester these away from the cell surface and inhibit their recycling or else induce a conformational change that precludes recognition by all class I antibodies tested. In either event, we propose that such a major perturbation of the class I MHC complex would likely downregulate the class I-mediated presentation of viral Ag required to initiate cell-mediated immunity to these viruses. PMID- 1309844 TI - Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function. AB - A well defined model of T cell-mediated hypersensitivity-type granulomatous inflammation induced by Schistosoma mansoni eggs was used to assess the role of IL-4 and IFN-gamma in granuloma development. Synchronized pulmonary granulomas were induced and isolated from S. mansoni-infected mice during vigorous (8 wk) and modulated (20 wk) stages of the disease. The sequential production of IL-4 and IFN was determined and related to temporal changes in granuloma macrophage production of IL-1, TNF, and superoxide anion (O2-). During the vigorous stage, IL-4 was produced on days 1 and 2 of granuloma formation, whereas IFN was released in greatest amounts on days 4 to 8. The peak of IL-4 occurred in a window between the peak of IL-1 (1 day) and maximal TNF production (8 to 16 days). Maximal O2- release tended to parallel IFN production. During the modulated stage when the inflammatory response is attenuated, IL-4 production was dramatically reduced as were levels of IL-1 and TNF, but IFN production persisted and maximum O2(-)-producing capacity was only delayed in onset. mAb specific for IL-4 and IFN were used to examine the effect of in vivo depletion of these cytokines on granuloma development. Administration of a single 1.0-mg dose of anti-IL-4 antibodies to mice with synchronously developing granulomas dramatically reduced granuloma size (40 to 50% suppression of area) during an 8 day study period, whereas antibodies to IFN had no effect on size. However, the latter treatment reduced giant cell formation. Our results indicate that granuloma development involves an orchestrated production of cytokines possibly resulting from sequential participation of different Th cell populations. Moreover, IL-4 is a pivotal cytokine in anamnestic cellular recruitment and subject to endogenous regulation. PMID- 1309845 TI - Role of T cell receptor V beta genes in Theiler's virus-induced demyelination of mice. AB - Intracerebral infection of certain strains of mice with Theiler's virus results in chronic immune-mediated demyelination in spinal cord. We used mouse mutants with deletion of the V beta class of TCR genes to examine the role of TCR genes in this demyelinating disease which is similar to multiple sclerosis. Quantitative analysis of spinal cord lesions demonstrated a markedly increased number and extent of demyelinated lesions in persistently infected RIII S/J mice which have a massive deletion of the TCR V beta-chain (V beta 5.2, V beta 8.3, V beta 5.1, V beta 8.2, V beta 5.3, V beta 8.1, V beta 13, V beta 12, V beta 11, V beta 9, V beta 6, V beta 15, V beta 17) compared with B10.RIII mice which are of identical MHC haplotype (H-2r) but have normal complement of V beta TCR genes. In contrast, infection of C57L (H-2b) or C57BR (H-2k) mice which have deletion of the V beta TCR genes (V beta 5.2, V beta 8.3, V beta 5.1, V beta 8.2, V beta 5.3, V beta 8.1, V beta 13, V beta 12, V beta 11, and V beta 9) resulted in few demyelinating lesions. Genetic segregation analysis of (B10.RIII x RIII S/J) x RIII S/J backcrossed mice and (B10.RIII x RIII S/J) F2 mice demonstrated correlation of increased susceptibility to demyelination with deletion of TCR V beta genes. The increase in number of demyelinating lesions correlated with increase in number of virus-Ag+ cells in spinal cord. These experiments provide strong evidence that the structural diversity at the TCR beta-complex can influence susceptibility to virus-induced demyelination. PMID- 1309846 TI - Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals. AB - To determine if infection with herpes simplex virus (HSV) type 2 is associated with human immunodeficiency virus (HIV) type 1 infection among patients attending sexually transmitted diseases clinics, a case-control study was done on coded sera from 179 HIV-1-infected patients and 367 age-, race-, and gender-matched HIV 1-seronegative patients. Although only 13 (2.3%) of 546 patients had a history of genital herpes treatment, 72% and 56.6%, respectively, had serologic evidence of prior infection with HSV-1 and -2. HSV-1 antibody prevalence was similar among both patient groups; however, HSV-2 antibodies were more common among those infected with HIV-1. Among heterosexual men, 62.7% of those infected with HIV-1 had HSV-2 antibodies compared with 46.7% of those not infected (P less than .01). The HSV-2 seroprevalence among women with or without HIV infection was 78.1% and 57.7%, respectively (P less than .02). A history of intravenous drug use and a reactive serologic test for syphilis were each independently associated with HIV 1 infection in heterosexuals. These data suggest that the two most common causes of genital ulcerative disease in the United States, genital herpes and syphilis, may contribute to increased risk for HIV-1 infection among heterosexuals. PMID- 1309847 TI - Host antibody response to viral structural and nonstructural proteins after hepatitis A virus infection. AB - Subgenomic hepatitis A virus (HAV) RNA sequences were translated in vitro to produce proteins representing the structural (P1) and nonstructural (P2 and P3) domains of the viral polyprotein. These proteins were used as antigens to detect the presence of antibodies in sera from acute and convalescent humans and an experimentally infected chimpanzee. All infected individuals tested had antibodies that recognized uncleaved P1 proteins as well as nonstructural proteins. Antibodies in sera from infected individuals recognized conformation dependent epitopes that were sensitive to SDS and heat treatment. Time-course studies of the experimentally infected chimpanzee showed that antibodies to the HAV proteins were detectable between 24 and 31 days after infection and persisted for greater than 6 months. Human sera remained positive for antibodies to both structural and nonstructural antigens for at least 2 1/2 years. The data suggest that HAV nonstructural proteins could be used as serologic markers for HAV diagnosis and for evaluating field trials of inactivated vaccines. PMID- 1309848 TI - Interleukin-4 inhibits human macrophage activation by tumor necrosis factor, granulocyte-monocyte colony-stimulating factor, and interleukin-3 for antileishmanial activity and oxidative burst capacity. AB - Interleukin (IL)-4 has been implicated in the pathogenesis of leishmaniasis in a murine model. Experiments were done to examine the effect of IL-4 on cytokine activation of macrophages. Interferon (IFN)-gamma, granulocyte-macrophage colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and IL-3 activate macrophages to inhibit replication of leishmaniae. IL-4 abrogated in a dose- and time-dependent manner the induction of antileishmanial activity by these cytokines. The depression of oxidative burst capacity is one mechanism by which IL-4 inhibits macrophage activation. IL-4 diminished in a dose- and time dependent manner the TNF alpha enhancement of oxidative capacity. Pretreatment with IL-4 for 48, 24, or 0 h, respectively, inhibited the generation of superoxide induced by TNF alpha by 90%, 60%, and 40%. Furthermore, IL-4 abrogated the enhancement of oxidative capacity by IFN-gamma, GM-CSF, and IL-3. These data suggest that IL-4 is a potent deactivator of macrophage antimicrobial functions and may contribute to the pathogenesis of visceral leishmaniasis. PMID- 1309849 TI - Antibody-mediated neutralization of human papillomavirus type 11 (HPV-11) infection in the nude mouse: detection of HPV-11 mRNAs. AB - The nu/nu mouse xenograft is the only experimental system permitting the growth of human papillomaviruses (HPV). Previous studies demonstrating inhibition of HPV 11 infection by antibodies against HPV-11 virions have used indirect markers of infection, such as graft size and histopathologic features. The presence of HPV 11 mRNAs was used as a direct marker of infection: Infectious HPV-11 was incubated with rabbit serum raised against purified HPV-11 virions or with the corresponding preimmune serum (controls) before use in the mouse xenograft model, and HPV-11 mRNAs were detected by a method using reverse transcription and amplification by polymerase chain reaction. Graft size, histopathologic features, and the presence of capsid antigen were also assessed. Six weeks after infection, 1 of 23 grafts in the test group contained HPV-11 mRNAs compared with 19 of 20 controls (P less than .001). Therefore, antibody-mediated inhibition of infection by HPV-11 leads to blockade of genomic expression and is thus consistent with active prevention of viral penetration, that is, neutralization. PMID- 1309850 TI - Antibodies to recombinant-derived glycoprotein B after natural human cytomegalovirus infection correlate with neutralizing activity. AB - Glycoprotein B (gB) of human cytomegalovirus (HCMV) was partially purified by lentil-lectin column chromatography from cells infected with an adenovirus-gB recombinant. This antigen, which contained specifically reactive proteins of approximately 130 and 55 kDa, was used to investigate gB antibody levels after natural HCMV infection in 48 individuals. All sera had IgG antibody to gB as detected by radioimmunoprecipitation (RIP) assays. Quantitative RIP showed a strong correlation between gB antibody and neutralizing activity (r = .74, P less than .001) but a weak correlation between gB antibody and total HCMV-specific IgG (r = .36, P less than .02). When gB antibody was specifically absorbed from 20 serum specimens, neutralizing antibody titer was reduced a median of 48% (range, 0-98%). These data confirmed that antibodies to gB are a large component of the neutralizing antibody response to HCMV and support a role for this protein in the development of subunit vaccines. PMID- 1309851 TI - Stroma is critical for preventing or permitting immunological destruction of antigenic cancer cells. AB - Inoculated immunogenic cancer cells after initial growth are potentially rejected by specific host immunity; however, the outcome of the interaction between host and inoculated cancer cells is a function of multiple factors including the route of inoculation, the number of cells, the density of antigens on the injected cancer cells, and the state of the immune system of the host. In the present study, we have examined a different kind of variable: the stroma that inoculated tumor cells initially reside in. The impetus to examine this factor arises from observations that cancer cells from several lines inoculated as fragments of solid tumors often grow progressively, whereas the same number or more than 10 fold larger numbers of identical type cells injected as a suspension are rejected, even though fragments or suspended cells are both tumorigenic at the same doses in nude mice. In the present studies, we found that: (a) indeed, cancer cells inoculated as fragments were more tumorigenic than cancer cells in suspension; (b) the tumorigenicity of suspended cancer cells was increased by injection of the cells into polyurethane sponge implants; (c) cancer cells were more tumorigenic embedded in syngeneic stroma than in transgenic antigenic stroma expressing the K216 major histocompatibility complex class I antigen; and (d) antigenic, bone marrow-derived, stromal components (presumably passenger leukocytes) were sufficient to cause rejection of immunogenic but antigenically unrelated cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309852 TI - RMA/S cells present endogenously synthesized cytosolic proteins to class I restricted cytotoxic T lymphocytes. AB - RMA/S is a mutant cell line with decreased cell surface expression of major histocompatibility complex class I molecules that has been reported to be deficient in presenting endogenously synthesized influenza virus nucleoprotein (NP) to cytotoxic T lymphocytes (CTL). In the present study we show that RMA/S cells can present vesicular stomatitis virus nucleocapsid protein, and, under some conditions, NP, to Kb-and Db-restricted CTL, respectively. Antigen presentation results from processing of cytosolic pools of endogenously synthesized proteins, and not the binding to cell surface class I molecules of antigenic peptides present in the virus inoculum or released from infected cells. Antigen processing of RMA/S differs, however, from processing by wild-type cells in requiring greater amounts of antigen, longer times to assemble or transport class I-peptide complexes, and in being more sensitive to blocking by anti-CD8 antibody. Thus, the antigen processing deficit in RMA/S cells is of a partial rather than absolute nature. PMID- 1309853 TI - Inhibition of cytotoxic T lymphocyte-induced target cell DNA fragmentation, but not lysis, by inhibitors of DNA topoisomerases I and II. AB - Cytotoxic T lymphocytes (CTL) kill their target cells via a contact-dependent mechanism that results in the perturbation of the target cell's plasma membrane and the fragmentation of the target cell's DNA into nucleosomal particles. The membrane disruption is presumed to be due to the action of perforin, while the DNA fragmentation is thought to be by the activation of an endogenous nuclease(s). DNA topoisomerases I and II are nuclear enzymes with inherent endonuclease activities. We have investigated their role in the CTL-induced DNA fragmentation process. We report that in CTL killing assays, the treatment of target cells with topoisomerase I and II inhibitors blocks the CTL-induced DNA fragmentation process, but not the lysis of the target cell. PMID- 1309854 TI - The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens. AB - Mice expressing the minor lymphocyte stimulation antigens, Mls-1a, -2a, or -3a, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V beta 3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor V beta element. PMID- 1309855 TI - Tumor necrosis factor production during human renal allograft rejection is associated with depression of plasma protein C and free protein S levels and decreased intragraft thrombomodulin expression. AB - Fibrin deposition is a common accompaniment of renal allograft rejection, indicating disruption of the normal physiologic balance between procoagulant and anticoagulant pathways. In vitro, tumor necrosis factor (TNF) induces endothelial expression of the procoagulant, tissue factor, and downregulation of thrombomodulin, a key component of the thrombomodulin/protein C (PC)/protein S (PS) pathway, which normally maintains an anticoagulant state by inactivating thrombin, preventing further thrombin formation by degrading factors Va and VIIIa, and decreasing plasminogen activator inhibitor activity. Raised levels of TNF were recently demonstrated within the blood of patients during episodes of renal allograft injection, and may be an early and discriminatory marker of rejection. This led us to investigate prospectively whether monitoring of serum TNF levels was of value clinically, and was associated with effects on circulating PC and PS levels, or alterations in intragraft thrombomodulin expression. Plasma samples (n = 454) were collected three times/week from all patients (n = 25) undergoing renal transplantation during a 9-month consecutive period, and assayed by ELISA and functional assays for TNF, PC, and free PS (FPS). Portions of renal biopsies, taken to evaluate episodes of acute deterioration of renal function, were evaluated by immunoperoxidase labeling for the presence and distribution of TNF, thrombomodulin, PC, PS, thrombin, fibrin, and factors V and VIII. Comparison of 78 plasma samples collected during 26 episodes of biopsy-proven acute cellular rejection with samples collected during periods of stable renal function (n = 349) showed that TNF levels rose significantly (390 +/- 242 pg/ml, p less than 0.01) above background levels 3 days before rising serum creatinine concentrations, and peaked (2,426 +/- 978 pg/ml) on the day of clinical rejection. PC-antigen (Ag) concentrations also decreased 3 days before rejection (68 +/- 13%, p less than 0.05), and were maximally depressed (49% +/- 16%, p less than 0.001) on the day of rejection. FPS levels were normal until the day before rejection (63% +/- 8%, p less than 0.01) and, like PC, were maximally depressed (43 +/- 10%) at rejection. Plasma TNF levels were significantly and inversely correlated with PC-Ag (p less than 0.001) and FPS (p less than 0.005) levels during rejection, regardless of whether such rejection episodes were steroid responsive or required OKT3 monoclonal antibody therapy. TNF, PC, and FPS levels were normal during episodes of cyclosporine toxicity and viral infection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1309856 TI - The unique N terminus of the herpes simplex virus type 1 large subunit is not required for ribonucleotide reductase activity. AB - Using purified bacterially expressed herpes simplex virus type 1 ribonucleotide reductase large subunit (R1) and the proteolytic enzymes chymotrypsin and trypsin, we have generated stable N-terminal truncations. Chymotrypsin removes 246 amino acids from the amino terminus to produce a fragment (dN246R1) which retains full enzymic activity and affinity for the small subunit (R2). Treatment of R1 with trypsin produces a 120K protein and a cleavage at amino acid residue 305 to produce a fragment (dN305R1) which remains associated with a 33K N terminal polypeptide. Although this 33K-dN305R1 complex retains full binding affinity for R2 its reductase activity is reduced by approximately 50%. Increasing the concentration of trypsin removes the 33K N-terminal polypeptide resulting in dN305R1 which, when bound to R2, has full ribonucleotide reductase activity. Like R1, dN246R1 and dN305R1 each exist as dimers showing that the first 305 amino acids of R1 are not necessary for dimer formation. These results indicate that, in structural studies of subunit interaction, dN246R1 or dN305R1 can be considered as suitable replacements for intact R1. PMID- 1309857 TI - Role of Epstein-Barr virus and interleukin 6 in the development of lymphomas of human origin in SCID mice engrafted with human tonsillar mononuclear cells. AB - Mice with severe combined immunodeficiency were inoculated intraperitoneally with 50 x 10(6) human tonsillar mononuclear cells (hu-TMCs) from Epstein-Barr virus (EBV) antibody seropositive or seronegative human subjects. Between 5 and 11 weeks later, 29.4% (10/34) of mice injected with hu-TMCs from EBV seropositive donors, but none of 34 animals receiving hu-TMCs from EBV seronegative donors, developed intraabdominal and/or intrathoracic tumours (P, 0.002). By means of in situ hybridization using alpha satellite DNA from human chromosome 17, all tumours produced after cell transfer from EBV seropositive donors were identified to be of human origin. Histologically the tumours resembled large cell lymphomas; the EBV genome was detected by in situ hybridization and EBV nuclear antigen by immunofluorescence in these tumours. The tumours were poly- or oligoclonal, and stained for human IgG and IgM, and less frequently IgA and IgD. Serum levels of human immunoglobulin in animals developing human tumours were significantly higher than in reconstituted mice without tumours and the sera exhibited polyoligo- or monoclonality in immunoelectrophoresis. Human interleukin 6 was detected in the serum of six of 10 animals with human lymphomas, but not in any animals without human lymphoma. PMID- 1309858 TI - Integration of hepatitis B virus DNA through a mutational hot spot within the cohesive region in a case of hepatocellular carcinoma. AB - Integrated hepatitis B virus (HBV) DNA previously cloned from a hepatocellular carcinoma genomic library derived from a Japanese patient was characterized further. Sequence analysis of restriction fragments bearing the virus-host junctions defined 3125 nucleotides of essentially un-rearranged HBV DNA of the adr subtype with the right junction mapping within the cohesive region at position 1970 and the left within the pre-core at position 1886. The right viral host junction contains a 7 bp repeat (TGTAGGC) and a possible 2 bp inversion. The integrated HBV DNA includes the complete open reading frames for core, pre-S, S and polymerase and a 3' truncated X gene, and lacks most of the pre-core. Integration has occurred at a mutational hot spot of the viral genome and appears to be located in a region of semi-repetitive genomic DNA 3' to the beta-globin gene cluster. PMID- 1309859 TI - Nucleotide sequence analysis of a homologue of herpes simplex virus type 1 gene US9 found in the genome of simian herpes B virus. AB - The 10K gene of simian herpes B virus (SHBV) has been located and the nucleotide sequence determined. Its relationship to homologous genes in other herpes-viruses has been examined. The SHBV 10K gene exhibits a closer relationship to its homologue in HSV-1 than to those in the other viruses studied. Nucleotide sequence identity of 61% was found between the HSV-1 and SHBV 10K genes, and 57% identity was found between the corresponding predicted protein sequences. A comparison of the amino acid sequences of the herpesvirus 10K proteins has revealed a number of conserved features. These are examined in relation to possible functions of the 10K proteins. Implications for evolutionary relationships between SHBV and other herpesviruses are discussed. PMID- 1309860 TI - Integration of bovine papillomavirus type 1 DNA and analysis of the amplified virus-cell junctions in transformed primary mouse fibroblasts. AB - We have analysed the site of bovine papillomavirus type 1 (BPV-1) DNA integration in clones originating from a transformed primary mouse fibroblast cell line established by transfection of linear BPV-1 DNA. Viral DNA was integrated at a single site in the host genome with an intact early region and an almost complete long control region. Sequence analysis showed that the BPV-1 DNA was integrated at the HindIII site (the enzyme used to linearize the BPV-1 DNA for transfection) with short deletions at both ends. These deletions correspond to a 534 bp segment spanning the 3' end of the L1 open reading frame and the replication enhancer element in the BPV-1 genome. The cellular sequences 5' to the viral integration site exhibited 85 to 97% identity to several sequences belonging to the mouse L1 family of long interspersed repetitive sequences. Cellular sequences 3' to the viral DNA exhibited no significant similarity to any known sequence. The BPV-1 sequences and the cellular flanking sequences were found to be amplified 45- to 50-fold. All the cell clones shared an identical integration site but one of the clones had an additional population of amplified and integrated BPV-1 DNA molecules with an internal deletion of 1136 bp in the late region. The significance of viral DNA integration at a murine long interspersed repetitive sequence containing an amplification-promoting sequence is discussed. PMID- 1309861 TI - Heterogeneous expression of the non-structural protein p80/p125 in cells infected with different pestiviruses. AB - In order to analyse the expression of the non-structural (ns) protein p80/p125 in cells infected with different pestiviruses at the protein level, radioimmunoprecipitations with the pestivirus-specific monoclonal antibody (MAb) BVD/C16 were performed. Cell lysates infected with cytopathic (cp) and non cytopathic (ncp) bovine viral diarrhoea (BVD) virus strains and isolates, and with hog cholera (HC) virus strains were analysed. From cpBVD virus-infected cells, the MAb precipitated one or more proteins corresponding to ns p125, displaying a marked size heterogeneity. In contrast, the lower Mr ns p80 proteins from all cpBVD virus strains and isolates analysed had identical electrophoretic motility. The ncpBVD virus strains displayed either one single band or a doublet of the p125 protein and no p80 cleavage products. The p125 proteins precipitated from HC virus-infected cells showed no size heterogeneity. The possibility is discussed that multiple recombination events, including both insertions or deletions in the genomes of ncpBVD viruses, may lead to the heterogeneous expression of the ns p125 in cpBVD virus populations. PMID- 1309862 TI - The L protein of vesicular stomatitis virus transcription complexes is specifically photolabelled by 5-azido-uridine 5'-triphosphate, an analogue of the RNA polymerase substrate uridine 5'-triphosphate. AB - A photoactive nucleotide analogue of UTP, 5-azido-uridine 5'-triphosphate (5 N3UTP), has been demonstrated to interact with the RNA polymerase of the vesicular stomatitis virus (VSV) transcription complex. Kinetic studies indicated that 5-N3UTP served as an efficient replacement for UTP in in vitro polymerase reactions. The Km for the azido analogue was 27 microM and that of the natural substrate, UTP, was 7 microM. Photolysis of [gamma-32P]5-N3UTP in the presence of VSV transcription complexes resulted in selective radio-labelling of the L protein. This photolabelling was saturable with an apparent Kd of 28 microM. The L protein was protected from [gamma-32P]5-N3UTP-mediated photolabelling by competing natural substrates (UTP, CTP, ATP, GTP). The stoichiometry of photoprobe incorporation into the transcription complex was close to unity with respect to the L protein. These data provide evidence that the nucleotide-binding domain of the VSV RNA polymerase contains amino acid residues of the L protein. PMID- 1309863 TI - Identification and characterization of serine/threonine protein kinase activity intrinsic to the L protein of vesicular stomatitis virus New Jersey. AB - A photoaffinity analogue of ATP, 8-azido-adenosine 5'-triphosphate (8-N3ATP), was used to probe ATP-binding sites in native transcription complexes of vesicular stomatitis virus (VSV) (New Jersey serotype). The analogue was found to be a substrate for a serine/threonine protein kinase that phosphorylated both the NS and L proteins of native complexes. The analogue failed to interact with the RNA polymerase, another ATP-utilizing activity associated with the transcription complex. Kinetic analyses of both ATP and 8-N3ATP utilization by the protein kinase yielded biphasic saturation curves. Photolysis of 8-N3ATP in the presence of VSV transcription complexes resulted in selective labelling of the L protein. The photolabelling of L was saturable and apparently biphasic. Photolabelling of the L protein was significantly reduced by competition with ATP whereas other nucleoside triphosphates (GTP, UTP and CTP) were ineffective competitors. The stoichiometry of photolabelling was 0.2 at 10 microM-8N3ATP and 1.3 at 100 microM ATP. These data provide chemical evidence for a virus-encoded serine/threonine protein kinase which resides on the L protein. PMID- 1309864 TI - Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain. AB - Major mitochondrial phospholipids were examined in rat brain after 30 minutes of reperfusion following 30- or 60-minute periods of ischemia to examine their changes and explore their relationship to mitochondrial dysfunction during postischemic reperfusion. The amount of phospholipids and the percentage of polyunsaturated fatty acid chains, which tended to decrease during 30 minutes of ischemia, recovered after reperfusion. However, after ischemia lasting for 60 minutes, these parameters did not recover but decreased further, suggesting progressive disruption of phospholipids by phospholipase A2 after reperfusion. These changes were particularly notable in cardiolipin, which is contained specifically in mitochondria. The changes were also closely associated with mitochondrial respiration and respiratory enzyme (cytochrome c oxidase and F0F1 adenosine triphosphatase) activities, which have been known to correlate with the amount of cardiolipin. These results suggest that phospholipid metabolism in mitochondrial membranes is an important factor bearing on the integrity of energy metabolism during postischemic reperfusion. PMID- 1309866 TI - False-positive results of tests for hepatitis C in autoimmune hepatitis. PMID- 1309865 TI - Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication. AB - We examined the efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) in children with markedly elevated blood lead (BPb) concentrations. Among 19 children with BPb concentrations of 50 to 69 micrograms/dl (2.41 to 3.33 mumol/L) who received a 5-day inpatient oral course of DMSA (1050 mg/m2 per day), the mean BPb concentration decreased by 61%; in four who received calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) (1000 mg/m2 per day intravenously), it decreased by 45% (p less than 0.0007). Urinary lead excretion was comparable in both groups. Treatment with DMSA was more effective than treatment with CaNa2EDTA in restoring metabolic activity to the heme pathway and was well tolerated even among nine patients who received concomitant iron supplementation and two who had homozygous deficiency of glucose-6-phosphate dehydrogenase. On discharge, these 19 children received either no chelation therapy or DMSA, 350 or 700 mg/m2 per day for 14 days on an outpatient basis. After 14 days the mean BPb values for the no-chelation, low-DMSA, and high-DMSA groups were 73%, 66%, and 50% of the pretreatment values, respectively. We conclude that a 5-day oral course of DMSA is effective in the treatment of children with severe lead poisoning. In addition, on an outpatient basis the administration of DMSA, 700 mg/m2 per day, is capable of delaying the typical rebound in BPb values and should ultimately reduce the need for repeated hospitalizations. PMID- 1309867 TI - Enzymatic diagnosis of nonketotic hyperglycinemia with lymphoblasts. AB - We developed a new enzymatic assay for the glycine cleavage system that used Epstein-Barr virus-transformed lymphoblasts instead of liver biopsy specimens. Patients with nonketotic hyperglycinemia from a deficiency of P-protein could be clearly distinguished from control subjects by activities in their lymphoblasts, suggesting the clinical usefulness of this method. PMID- 1309868 TI - Effect of chronic treatment with the calcium entry blocker, isradipine, on vascular calcium overload produced by vitamin D3 and nicotine in rats. AB - Treatment of young rats with vitamin D3 and nicotine produced a 35-fold increase in the calcium content of the aorta and a 4-fold increase in the calcium content of the mesenteric arterial bed. Blood pressure was not modified. In vitro, aortic rings and mesenteric arterial bed preparations from such animals showed diminished vasoconstrictor responses to norepinephrine. After precontraction with norepinephrine, the endothelium-dependent vasodilator, carbachol, produced vasorelaxation. This latter effect was attenuated in aortic rings and mesenteric arterial bed preparations from animals previously treated with vitamin D3 and nicotine, but the vasodilator effect of sodium nitroprusside (which is independent of the endothelium) was unchanged. Prolonged treatment with the calcium entry blocker, isradipine, at a dose (1 mg/kg, i.p.) which had no effect on blood pressure, prevented calcium overload of the mesenteric arterial bed, but did not modify aortic calcium overload. Isradipine treatment had no effect on vasoconstrictor responses to norepinephrine in vitro. Such treatment did, however, restore the endothelium-dependent vasodilator effect of carbachol in the mesenteric arterial bed (but not in aortic rings). In conclusion, in a rat model of vascular calcium overload produced by administration of vitamin D3 plus nicotine, chronic treatment with a low dose of the calcium entry blocker, isradipine, restored the endothelium-dependent vasorelaxant effect of carbachol in the mesenteric arterial bed, but not in the aorta. PMID- 1309869 TI - Block of sodium channel current by anticonvulsant U-54494A in mouse neuroblastoma cells. AB - (+/- ) -cis-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzamide (U 54494A), structurally related to a kappa opioid agonist U-50448H, is a potent anticonvulsant without analgesic or sedative effects of the opioid agonist in intact animal studies (VonVoigtlander et al., 1987). To explore the mechanism of its anticonvulsant action, we investigated the interaction of U-54494A with the voltage-gated sodium channel using the whole cell patch clamp technique in mouse neuroblastoma cells (NIE-115). The drug reversibly and dose-dependently reduced the tetrodotoxin-sensitive inward Na current without affecting its activation or inactivation kinetics or the reversal potential. Nearly half of this resting block by 50 microM U-54494A at a holding potential of -80 mV was reversed upon further hyperpolarization to -120 mV. We also observed a hyperpolarization shift (9.3 mV) of the steady-state slow inactivation curve in the presence of 50 microM drug with no shift in the steady-state activation or the fast inactivation curves. These results indicate that the drug interacts with the resting and the slowly inactivated channels. The drug appears not to interact with the open state, judging from the absence of a time-dependent block in chloramine-T-treated cells. The recovery rate of the inactivated channel was markedly delayed by the drug, and apparently is responsible for its use-dependent block upon repetitive depolarizations. Our results suggest that voltage- and use-dependent block of the Na channel by U-54494A may be an important pharmacological basis for its anticonvulsant action. PMID- 1309870 TI - Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, SK&F 108566. AB - The angiotensin II (AII) antagonist activity of (E)-alpha-[[2-butyl-1-[(4 carboxyphenyl)methyl]-1H-imidazol-5- yl]methylene]-2-thiophenepropanoic acid (SK&F 108566), was examined in a number of in vitro and in vivo assays. In rat and human adrenal cortical membranes, SK&F 108566 displaced specifically bound [125I]AII with IC50 of 9.2 and 3.9 nM, respectively. SK&F 108566 also inhibited [125I]AII binding to human liver membranes (IC50 = 1.7 nM) and to rat mesenteric artery membranes (IC50 = 1.5 nM). In rabbit aortic smooth muscle cells, SK&F 108566 caused a concentration-dependent inhibition of AII-induced increases in intracellular Ca++ levels. In rabbit aortic rings, SK&F 108566 produced parallel rightward shifts in the AII concentration-response curve without affecting the maximal contractile response. Schild analysis of the data yielded a KB value of 0.26 nM and a slope not different from 1, indicative of competition antagonism. SK&F 108566 had no effect on the contractile responses to KCl, norepinephrine or endothelin in rabbit aorta. In conscious normotensive rats, i.v. administration of SK&F 108566 (0.01-0.3 mg/kg) produced dose-dependent parallel shifts in the AII pressor dose-response curve. Administration of SK&F 108566 (3-10 mg/kg) intraduodenally or intragastrically to conscious normotensive rats resulted in a dose-dependent inhibition of the pressor response to AII (250 ng/kg, i.v.). At 10 mg/kg, i.d., significant inhibition of the pressor response to AII was observed for 3 hr. In this same rat model, SK&F 108566 had no effect on base-line pressure or on the pressor response to norepinephrine or vasopressin. The data demonstrate that SK&F 108566 is a potent, highly selective, competitive nonpeptide AII antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309871 TI - Multiple actions of the leukotriene B4 receptor antagonist SC-41930. AB - 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H-1 benzopyran-2-carboxylic acid (SC-41930), a leukotriene B4 (LTB4) receptor antagonist with anti-inflammatory activity in animal models of colitis, was evaluated for effects on superoxide, LTB4 and prostaglandin E2 production. SC 41930 inhibited human neutrophil (PMN) superoxide generation maximally stimulated by f-Met-Leu-Phe (IC50 4 microM) and C5a (IC50 approximately 12 microM). Moreover, postreceptor stimulation of superoxide production by NaF (a G protein activator), but not by phorbol myristate acetate, was significantly inhibited by SC-41930, indicating that SC-41930 may act via attenuation of a G protein mediated signal transduction. SC-41930 also inhibited A23187-stimulated LTB4 production (IC50 5.3 microM) in human PMN as well as LTB4 (IC50 2.1 microM) and prostaglandin E2 (IC50 2.9 microM) production in HL-60 cells. When coinjected intradermally (400 micrograms/site), SC-41930 inhibited A23187-stimulated increases in LTB4 levels in guinea pig skin. SC-41930 inhibited human synovial phospholipase A2 (IC50 72 microM), A23187-stimulated 5-hydroxy-eicosatetranoic acid production in human PMN (IC50 8.5 microM), and rat peritoneal leukotriene A4 hydrolase (IC50 20 microM), but not ram seminal vesical cyclooxygenase. The results suggest that the anti-inflammatory activity of SC-41930 could be attributed to postreceptor inhibition of inflammatory mediator production by PMN and other cells in addition to antagonism of PMN LTB4 receptors. PMID- 1309872 TI - Pharmacological profile of a series of bicyclic cannabinoid analogs: classification as cannabimimetic agents. AB - Opening of the pyran ring of delta 9-tetrahydrocannabinol (THC) produces cannabidiol, a bicyclic cannabinoid devoid of many pharmacological properties produced by delta 8-THC or delta 9-THC. Interestingly, the bicyclic compound CP 47,497 (VI) has been described as producing many of the pharmacological effects produced by delta 9-THC, and another related bicyclic analog CP-55,940 (XIV) has been used to successfully define a cannabinoid binding site. A series of 16 bicyclic analogs of VI and XIV were evaluated and compared with the pharmacological profile of cannabidiol, delta 8-THC and delta 9-THC. The goals of the studies described herein were to determine whether these bicyclic analogs possess similar pharmacological properties of delta 9-THC, to compare pharmacological activity after s.c. and i.v. administration, and to evaluate the structure-activity relationship of this series of analogs for further insight into cannabinoid mechanism of action. Each analog was evaluated for its ability to produce hypoactivity, hypothermia, antinociception and catalepsy in mice. The ED50 values generated from these assays were averaged to provide an index of activity. The ED50 values for delta 9-THC varied from 1.0 to 1.5 mg/kg, giving an overall index of activity of 1.3. The index for delta 8-THC was 6.0, making this isomer 4-fold less potent. Although several bicyclic analogs (V, VI, VII, VIII, XI, XII, XIV and XVI) proved to be truly cannabimimetic, three (IV, IX and X) were sufficiently unique to be classified as noncannabimimetic. The index of activity of cannabimimetic bicyclic analogs varied from 0.2 to 2.2, although some minor differences between the bicyclics and delta 9-THC exist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309873 TI - Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. AB - Tramadol hydrochloride produced dose-related antinociception in mouse abdominal constriction [ED50 = 1.9 (1.2-2.6) mg/kg i.p.], hot-plate [48 degrees C, ED50 = 21.4 (18.4-25.3) mg/kg s.c.; 55 degrees C, ED50 = 33.1 (28.2-39.1) mg/kg s.c.] and tail-flick [ED50 = 22.8 (19.2-30.1) mg/kg s.c.] tests. Tramadol also displayed antinociceptive activity in the rat air-induced abdominal constriction [ED50 = 1.7 (0.7-3.2) mg/kg p.o.] and hot-plate [51 degrees C, ED50 = 19.5 (10.3 27.5) mg/kg i.p.] tests. The antinociceptive activity of tramadol in the mouse tail-flick test was completely antagonized by naloxone, suggesting an opioid mechanism of action. Consistent with this, tramadol bound with modest affinity to opioid mu receptors and with weak affinity to delta and kappa receptors, with Ki values of 2.1, 57.6 and 42.7 microM, respectively. The pA2 value for naloxone obtained with tramadol in the mouse tail-flick test was 7.76 and was not statistically different from that obtained with morphine (7.94). In CXBK mice, tramadol, like morphine, was devoid of antinociceptive activity after intracerebroventricular administration, suggesting that the opioid component of tramadol-induced antinociception is mediated by the mu-opioid receptor. In contrast to the mouse tail-flick test and unlike morphine or codeine, tramadol induced antinociception in the mouse abdominal constriction, mouse hot-plate (48 degrees or 55 degrees C) or rat hot-plate tests was only partially antagonized by naloxone, implicating a nonopioid component. Further examination of the neurochemical profile of tramadol revealed that, unlike morphine, it also inhibited the uptake of norepinephrine (Ki = 0.79 microM) and serotonin (0.99 microM). The possibility that this additional activity contributes to the antinociceptive activity of tramadol was supported by the finding that systemically administered yohimbine or ritanserin blocked the antinociception produced by intrathecal administration of tramadol, but not morphine, in the rat tail-flick test. These results suggest that tramadol-induced antinociception is mediated by opioid (mu) and nonopioid (inhibition of monoamine uptake) mechanisms. This hypothesis is consistent with the clinical experience of a wide separation between analgesia and typical opioid side effects. PMID- 1309874 TI - The acute renal actions of angiotensin converting enzyme inhibitors in the sodium depleted conscious primate are mediated by inhibition of the renin-angiotensin system. AB - The purpose of this study was to determine if the changes in renal function acutely produced by an inhibitor of angiotensin converting enzyme (ACE) in the sodium-depleted conscious marmoset can be explained primarily by blockade of the renin-angiotensin system. Intravenous injection of a dose of the ACEI, enalaprilate (2 mg/kg), that produced a maximal lowering of blood pressure (BP), also decreased renal vascular resistance and increased renal blood flow. Glomerular filtration rate was unchanged by enalaprilat, leading to a fall in the filtration fraction. In comparison, a dose of the renin inhibitory monoclonal antibody, R-3-36-16 (0.1 mg/kg), that also produced a maximal fall in BP, produced similar changes in renal hemodynamics to those observed after administration of the ACEI. Combined administration of 2 mg/kg enalaprilat and 0.1 mg/kg R-3-36-16 produced changes in BP and renal hemodynamics similar to those produced by the same doses of either agent administered alone. Enalaprilat (2 mg/kg) significantly increased urine volume (UV) and urinary sodium excretion (UNaV). In contrast, these parameters were not significantly altered by 0.1 mg/kg R-3-36-16. However, when given at a 10-fold higher dose, the monoclonal antibody produced an increase in UNaV and UV identical to that produced by the ACEI alone. Enalaprilat did not increase UV and UNaV excretion to a greater extent than the high dose of the renin inhibitory antibody. These results demonstrate that acute administration of an ACEI affects BP and renal function in the sodium-depleted conscious primate primarily by inhibition of the renin-angiotensin system. PMID- 1309875 TI - Anti-inflammatory activity of BF389, a Di-T-butylphenol, in animal models of arthritis. AB - Biofor 389 (BF389), dihydro-4-[[3,5-bis(1,1-dimethyl)-4-hydroxyphenyl] methylene] 2-methyl-2H-1,2-oxazin-3(4H)-one, was tested for anti-inflammatory activity in various animal models of arthritis. Initial evaluation in the lipoidalamine (LA) arthritis model in rats (5-day dosing protocol) resulted in an oral ED50 of 4.9 mg/kg for inhibition of paw swelling. No effects on splenomegaly were observed, suggesting that the compound was efficacious as a result of anti-inflammatory rather than immunomodulatory effects. BF389 was efficacious in interleukin 1 (IL 1)-enhanced type II collagen arthritis in rats (oral ED50 less than 1.0 mg/kg) as assessed by paw volume measurement and histologic evaluation of joints. Mice with IL-1-enhanced type II collagen arthritis given 30 mg/kg of BF 389 had significantly lower histological scores for joint damage than did untreated controls. Normal rats given single oral doses of BF389 had significant suppression of arachidonate-stimulated whole blood prostaglandin E2 and thromboxane B2 production 2 hr postdosing (ED50 = 0.1 mg/kg). Leukotriene B4 production in these animals was not decreased. After it became apparent that the compound was a potent inhibitor of prostaglandin production in vivo, a study was done to compare the efficacy and toxicity of BF389 with several currently marketed nonsteroidal anti-inflammatory drugs, piroxicam, naproxen and diclofenac. Lipoidalamine-injected rats were given daily oral doses of BF389 or the comparators for 21 days. Quantitation of effects on arthritis on day 21 resulted in ED50 values of 0.9 mg/kg (BF389), 3.9 mg/kg (naproxen), 4.9 mg/kg (diclofenac) and 0.6 mg/kg (piroxicam).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309876 TI - Agonist and antagonist activity of kappa opioids in the squirrel monkey: I. Antinociception and urine output. AB - The present study was conducted to evaluate the agonist and antagonist properties of kappa opioids in the squirrel monkey shock titration procedure. The opioid antagonist naltrexone, the kappa agonists U50,488, bremazocine, ethylketazocine and tifluadom, and the mu agonist l-methadone were administered alone and in combination with a single dose of the mu agonist morphine. When administered alone, all opioids except naltrexone produced dose-dependent increases in median shock level (the intensity below which monkeys maintained shock 50% of the time). In addition, all kappa agonists produced increases in urine output, whereas naltrexone and l-methadone did not. When combined with morphine, naltrexone and all kappa agonists antagonized, at least partially, morphine-induced increases in median shock level, whereas l-methadone did not. Naltrexone and the four kappa agonists also shifted an l-methadone dose-effect curve rightward in a parallel manner; however, the shifts produced by naltrexone were greater in magnitude than those produced by the kappa agonists. These studies demonstrate that a variety of kappa agonists can act as mu antagonists in a primate model of analgesia, although antagonist activity of kappa opioids appears to be limited by their agonist activity in this procedure. Order of potency among the kappa agonists for analgesic, diuretic and antagonist effects was very similar (bremazocine greater than ethylketazocine greater than tifluadom greater than or equal to U50,488), as was the dose range for peak diuretic and antagonist effects, suggesting that mu antagonism among kappa agonists may be kappa-mediated in the squirrel monkey. PMID- 1309877 TI - Agonist and antagonist activity of kappa opioids in the squirrel monkey: II. Effect of chronic morphine treatment. AB - The kappa opioid agonists U50,488, bremazocine, ethylketazocine and tifluadom and the opioid antagonist naltrexone were examined alone and in combination with morphine in a squirrel monkey shock titration procedure, before and during chronic morphine administration. Before chronic morphine administration (prechronic phase), all opioids except naltrexone produced dose-dependent increases in median shock level when administered alone. When combined with a dose of morphine that increased median shock level to 90% of maximum (ED90), naltrexone, U50,488 and bremazocine completely antagonized the effects of morphine in most monkeys, whereas ethylketazocine and tifluadom partially antagonized the effects of this dose of morphine. After 10 weeks of daily morphine administration (chronic phase), the average ED90 for morphine was increased 1 log unit. In contrast, average ED50 values for U50,488, bremazocine and tifluadom were decreaed 1/4 to 1/2 log unit, whereas the average ED50 for ethylketazocine did not change from the prechronic to chronic phases. When combined with morphine during the chronic phase, naltrexone completely antagonized the effects of the morphine ED90 at approximately the same doses as during the prechronic phase. In contrast, antagonist activity decreased for U50,488 and bremazocine, increased for ethylketazocine and did not change consistently for tifluadom, compared with the prechronic phase. The present study demonstrates that chronic morphine administration alters both the agonist and antagonist activity of kappa opioids. Changes in antagonist activity of kappa opioids after chronic morphine administration may be explained by concurrent changes in their agonist potency and the extent to which their agonist effects are mu-mediated. PMID- 1309878 TI - In vivo characterization of the pharmacodynamic interaction of a benzodiazepine agonist and antagonist: midazolam and flumazenil. AB - The pharmacokinetic and pharmacodynamic interaction between the benzodiazepine agonist midazolam and antagonist flumazenil was quantified in vivo in rats, using effect parameters derived from aperiodic EEG analysis. The benzodiazepine-induced increase in amplitudes in the 11.5 to 30 Hz (beta) frequency band of the EEG was used as effect measure. A competitive interaction model was derived that could describe and predict the time course of EEG effect after administration of several combinations of midazolam and flumazenil. Two approaches to derive the interaction model were evaluated. In a first experiment, rats received 10 or 20 mg/kg midazolam i.v. in 15 min during a steady-state infusion of flumazenil at a rate of 0, 0.25, 0.5 or 1 mg/kg/hr. The EEG was continuously measured and frequent blood samples were taken to determine the pharmacokinetics of the drugs. Flumazenil did not influence the pharmacokinetics of midazolam, but a significant reduction in the clearance of flumazenil was observed in the presence of midazolam. Flumazenil did not possess any intrinsic efficacy with regard to the EEG effect measure. With increasing flumazenil concentrations, a parallel shift in the concentration-EEG effect relationship of midazolam was observed, confirming the competitive nature of the interaction. An agonist-antagonist interaction model was used to quantify the interaction, yielding the pharmacodynamic parameters of midazolam [(mean +/- S.E.): Emax = 80 +/- 5 microV/sec, EC50 = 35 +/- 3 ng/ml and N = 1.1 +/- 0.2] and flumazenil: EC50 = 24 +/- 2 ng/ml and N = 1.6 +/- 0.1. In a second experiment, rats received 5 mg/kg flumazenil or placebo i.v. in 10 min during a steadystate infusion of midazolam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309879 TI - Opposite effects of enantiomers of clofibric acid derivative on rat skeletal muscle chloride conductance: antagonism studies and theoretical modeling of two different receptor site interactions. AB - The R-(+) enantiomer of 2-(p-chlorophenoxy) propionic acid (CPP) produces a biphasic effect on chloride channel conductance (GCl) of rat skeletal muscle, increasing GCl at low concentrations and decreasing it at concentrations greater than 10 microM; on the other hand, the S-(-) isomer mostly blocks GCl in a concentration-dependent manner. To explain the peculiar behavior of these compounds, a theoretical model based on the presence of two opposing receptor populations controlling chloride channel conductance has been used to fit the experimental data of the concentration-response curves of both S-(-) and R-(+) CPP. An analysis performed by means of the algebraic summation of two logistic terms suggests a reasonable merit of the proposed model and explains the resultant effect of each optical form as follows: S-(-) acts as a full agonist on an inhibitory sites, whereas R-(+) acts as a full agonist at both the inhibitory and excitatory sites. Antagonism studies appear to be consistent with the proposed model. Dose-response curves in which the block of GCl by the S-(-) isomer was evaluated in the presence of the R-(+) isomer (3-10 microM) clearly showed an antagonistic interaction between the two enantiomers, with an increase in the S-(-) concentration for half-maximal block. The antagonism was overcome by high concentrations of S-(-), and this might be consistent with the hypothesis that the block of GCl is modulated by an inhibitory site at which the two enantiomers compete. PMID- 1309880 TI - Effects of the amphiphilic peptides melittin and mastoparan on calcium influx, phosphoinositide breakdown and arachidonic acid release in rat pheochromocytoma PC12 cells. AB - Two amphiphilic peptides from hymenopterid insects, melittin and mastoparan, stimulate secretion in a variety of cell types. In PC12 cells, both peptides stimulate calcium influx with melittin some 20-fold more potently than mastoparan. Melittin stimulates both breakdown of phosphoinositides (Pl) by phospholipase C to yield inositol phosphates and hydrolysis of phospholipids by phospholipase A2 to release arachidonic acid (AA). Mastoparan stimulates Pl breakdown, but has no effect on AA release. Maximal stimulation of Pl breakdown occurs at 1 to 2.5 micrograms/ml melittin and 30 micrograms/ml mastoparan, whereas maximal stimulation of AA release occurs at 2 to 5 micrograms/ml melittin. Organic calcium channel blockers (nifedipine, verapamil, diltiazem) have little or no effect on responses to the peptides. The influx of calcium elicited by melittin or mastoparan is completely or nearly completely blocked by inorganic calcium channel blockers (Co++, Mn++, Cd++). Mn++ and Cd++ inhibit melittin-induced Pl breakdown and AA release and mastoparan-induced Pl breakdown. Co++ has no effect on melittin-induced Pl breakdown and potentiates mastoparan induced Pl breakdown. Pertussis toxin has no effect on the Pl breakdown induced by either peptide. The responses to melittin and mastoparan in PC12 cells are compared to those reported for maitotoxin. PMID- 1309881 TI - Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1. AB - Bradykinin has been implicated in the pathogenesis of inflammatory arthritis by virtue of its potent proinflammatory properties. We have previously shown bradykinin to be a potent stimulus for the release of prostanoids from interleukin-1 (IL-1)-treated, but not untreated, human synovial cells. We hypothesize that one mechanism by which IL-1 induces responsiveness to bradykinin is by upregulation of number or affinity of kinin receptors on human synovial cells. We performed [3H]bradykinin binding studies in intact human synovial tissue and in cultured human synovial cells. Specific, saturable [3H]bradykinin binding sites in intact synovia were identified by autoradiographic localization and were present in much higher density in rheumatoid, than in osteoarthritis, synovia. In untreated human synovial cells in culture, a single (B2) class of kinin binding sites with a Kd of 2.3 nM and Bmax of 58 +/- 9 fmol/10(6) cells was demonstrated. In matched experiments, IL-1 treatment enhanced specific [3H]bradykinin binding 1.5- to 2.0-fold above that observed in untreated cells. This enhancement was attributable to an increase in Bmax (53 +/- 4 vs. 105 +/- 24 fmol/10(6) cells in untreated and IL-1-treated cells, respectively), rather than an alteration in Kd (1.7 and 1.4 nM, respectively). The potencies of a series of kinin analogs and antagonists and unrelated peptides in displacing [3H]bradykinin from IL-1-treated cells correlated well with their abilities to induce prostanoid release. These studies provide novel information regarding the nature of kinin receptors in intact human synovia and in cultured human synovial cells, their regulation by IL-1 and their role in IL-1-treated cells in kinin-mediated prostaglandin E2 production. PMID- 1309882 TI - Receptor-coupled G proteins mediate contraction and Ca++ mobilization in isolated intestinal muscle cells. AB - Guanosine 5'-O-(gamma-thio)triphosphate (GTP[S]), NaF and cholecystokinin octapeptide (CCK-8) were used to examine the participation of G proteins in agonist-induced contraction of smooth muscle cells isolated separately from circular and longitudinal muscle layer of guinea pig intestine. All three agents stimulated inositol 1,4,5-triphosphate (InsP3) production and protein kinase C activity to the same extent in permeabilized (GTP[S] and CCK-8) and nonpermeabilized (NaF and CCK-8) muscle cells. InsP3 production was 9 to 13 times higher in circular muscle cells consistent with preferential hydrolysis of phosphatidylinositol 4,5-biphosphate in this cell type. InsP3 production and protein kinase C activation in permeabilized muscle cells were abolished by guanosine 5'-O-(beta-thio)diphosphate (10 microM). Maximal concentrations of GTP[S] (100 microM), CCK-8 (1 nM) and InsP3 (1 microM) elicited similar increases in [Ca++]i, net 45Ca++ efflux and contraction in permeabilized circular, but not longitudinal, muscle cells [( Ca++]i: 224 +/- 35 nM, 279 +/- 29 nM and 288 +/- 45 nM increase above basal level; 45Ca++ efflux: 35 +/- 2%, 34 +/- 3% and 37 +/- 3% decrease in cell Ca++ content; contraction: 26 +/- 2%, 24 +/- 2% and 25 +/- 2% decrease in cell length). The responses to GTP[S] and CCK-8 were abolished by guanosine 5'-O-(beta-thio)diphosphate (10 microM) and heparin (10 micrograms/ml), whereas the response to InsP3 was abolished by heparin only. Maximal concentrations of NaF and CCK-8 elicited similar increases in [Ca++]i and contraction in nonpermeabilized circular and longitudinal muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309883 TI - Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways. AB - omega-Conotoxin GVIA, a peptide derived from the marine snail Conus geographus, is an antagonist of the neuronal N type voltage-sensitive calcium channels associated with neurotransmitter release. The present study investigated effects of this peptide on neurally mediated responses in airways isolated from the guinea pig to determine whether airway nerves are modulated by omega-conotoxin sensitive calcium channels. Electrical field stimulation was used to induce neurally mediated tachykininergic excitatory responses in guinea pig bronchus and cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea. Exogenous agonists were administered to induce contractile (acetylcholine, substance P) or relaxation (sodium nitroprusside) responses. Tissues were incubated with omega-conotoxin (1 microM) or its vehicle (10 mM acetic acid) for 30 min before establishing frequency- or concentration-response relationships to the various stimuli. Frequency-response curves for neurally mediated cholinergic, nonadrenergic nocholinergic inhibitory and tachykininergic responses were shifted to the right by omega-conotoxin to a similar extent (4- to 5-fold). omega-Conotoxin had no effect on contractile responses elicited by exogenous acetylcholine or substance P or on relaxations induced by sodium nitroprusside. These findings indicate that neurotransmission in afferent tachykininergic kininergic nerves and in efferent cholinergic excitatory and nonadrenergic noncholinergic inhibitory nerves in the airways is modulated by a prejunctional omega-conotoxin-sensitive mechanism. PMID- 1309884 TI - Immunochemical characterisation of a 29-Kda surface-associated molecule of Entamoeba histolytica and its recognition by serum from patients with amoebiasis. AB - A 29-Kda cytotoxic molecule of axenically-grown pathogenic Entamoeba histolytica (strain HM1) was purified from an amoebic extract by immuno-affinity chromatography with monoclonal antibodies. Immunoreactivity of the purified 29 Kda molecule altered significantly (p less than 0.01) after exposure to heat or trypsin, but remained unaltered after treatment with sodium metaperiodate. The 29 Kda molecule was recognised by serum from each of 13 patients with amoebic liver abscess. In an ELISA system, the molecule produced significantly higher (p less than 0.01) OD readings with these serum samples than with samples from asymptomatic cyst passers. No serum from healthy subjects or from patients with idiopathic ulcerative colitis or giardiasis had antibodies that reacted with the 29-Kda molecule. The immune response to the 29-Kda amoebic protein in man may indicate a specific role for this molecule in invasive amoebiasis. PMID- 1309885 TI - Model for the differential stabilities of rhinovirus and poliovirus to mild acidic pH, based on electrostatics calculations. AB - Previous calculations of electrostatic interactions in the rhinovirus capsid have identified a subset of histidine residues, paired with lysine or arginine, that may be involved in pH-induced conformational changes related to viral uncoating. Further calculations with the finite difference method, accounting for the dielectric environment of the ionizable groups, suggest that charge burial in the crystal conformation will prevent protonation of these histidine residues in the pentamer-pentamer interface. Calculations with a modelled pentamer-pentamer interface in which three beta-strands are removed recover mildly acidic pKa values for the histidines. These results are discussed in the context of the structural interactions of these three beta-strands, which form a beta-sheet extension from the rest of the capsid, and with regard to the conformation of the homologous beta-sheet extension in poliovirus, which also possesses homologous histidine-lysine/arginine pairs. A model is developed in which the structural stability of the beta-sheet extension is related to the difference in acid stability of rhinovirus and poliovirus. It is suggested that, for poliovirus prior to cell receptor binding, the beta-sheet extension is stable at pH 3, the pentamer-pentamer interface histidines remain buried, and the virus is acid stable. Cell receptor binding of poliovirus destabilizes the beta-sheet extension and the acid lability that is proposed to result could be involved in viral uncoating. For rhinovirus it is suggested that the observed conformational change in the absence of cell receptor binding involves a further acidic pH-activated process or conformational fluctuations that rearrange the beta-sheet extension and expose the pentamer-pentamer interface histidine residues to the acidic medium. Sequence analysis and electrostatics calculations reveal an aspartic acid in the beta-sheet extension that may have different pKa values in rhinovirus and poliovirus. PMID- 1309886 TI - Interdomain salt bridges modulate ligand-induced domain motion of the sulfate receptor protein for active transport. AB - The refined crystal structure of the liganded form of the Salmonella typhimurium sulfate-binding protein, a periplasmic receptor of active transport, is made up of two globular domains bisected by a deep cleft wherein the dehydrated sulfate is completely engulfed and bound by hydrogen bonds and van der Waals' forces. Two salt bridges (between Glu15 and Arg174 and between Asp68 and Arg134) span the cleft opening. To elucidate the role of the inter-domain salt bridges in the ligand-induced domain motion, the acidic residues were changed (singly and together) to their corresponding amide side-chains by site-directed mutagenesis of the recombinant Escherichia coli sulfate-binding protein. Rapid kinetics and equilibrium measurements of sulfate binding to the purified mutant proteins demonstrate that these salt bridges stabilize the closed liganded form of the receptor and modulate the rate of cleft opening. Our results have new implications in understanding the dynamics of many other multidomain proteins that undergo similar large-scale domain motions. PMID- 1309887 TI - NF-IL6, a member of the C/EBP family, regulates E1A-responsive promoters in the absence of E1A. AB - A cDNA encoding NF-IL6, an interleukin-6 (IL-6)-regulated human nuclear factor of the C/EBP family, is demonstrated to complement the transactivation function of E1A. The endogenous NF-IL6 level varies according to cell type and correlates positively with an IL-6-regulated cellular E1A-substituting activity that was described recently (J.M. Spergel and S. Chen-Kiang, Proc. Natl. Acad. Sci. USA 88:6472-6476, 1991). When expressed by transfection in cells which contain low levels of NF-IL6 and are incapable of complementing the function of E1A proteins, NF-IL6 also transactivates the E1A-responsive E2ae and E1B promoters, to the same magnitude as E1A. Activation by NF-IL6 is concentration dependent and sequence specific: mutational studies of the E2ae promoter suggest that the promoter proximal NF-IL6 recognition site functions as a dominant negative regulatory site whereas the promoter-distal NF-IL6 recognition site is positively regulated at low NF-IL6 concentrations and negatively regulated when the NF-IL6 level is high. Consistent with these functions, NF-IL6 alone is sufficient to complement an E1A deletion mutant dl312 in viral infection, when expressed at appropriate concentrations. These results identify NF-IL6 as a sequence-specific cellular nuclear factor which regulates E1A-responsive genes in the absence of E1A. PMID- 1309888 TI - Simian virus 40 large T-antigen expression decreases the G1 and increases the G2 + M cell cycle phase durations in exponentially growing cells. AB - The effect of simian virus 40 large T-antigen (Tag) expression on the cell cycle of exponentially growing, established, mouse NIH 3T3 fibroblasts was examined by using a sensitive flow cytometric assay to analyze nonselected cells immediately after infection with a Tag-encoding recombinant retrovirus. Tag expression resulted in reduced percentages of G1-phase cells and increased percentages of S- and G2 + M-phase cells compared with cell populations infected with a control virus not encoding the Tag gene. Cell cycle-blocking drugs were used to examine the exit rate for each of the cell cycle phases, G1, S, and G2 + M, for Tag expressing and Tag-nonexpressing cells growing in the same cell culture dish. As a result of Tag expression, the duration of the G1 phase was decreased (average G1-phase exit duration decreased by 18%) and the duration of the G2 + M phase was increased (average G2 + M exit duration increased by 29%). The duration of S phase was unaffected by Tag expression. PMID- 1309889 TI - Characterization of early pathogenic effects after experimental infection of calves with bovine immunodeficiency-like virus. AB - The early pathogenic effects of bovine immunodeficiency-like virus (BIV) were studied in calves experimentally inoculated with BIV. All animals inoculated with BIV R29-infected cells seroconverted by 6 weeks postinoculation, and BIV was recoverable from each animal at 2 weeks postinoculation. However, levels of BIV replication in vivo appeared to be low. In situ hybridization studies indicated that during peak periods of viral replication in vivo, less than 0.03% of peripheral blood mononuclear cells were expressing detectable levels of viral RNA. Moreover, the levels of viral RNA in these cells in vivo were less than 1/10 the levels observed in persistently infected cells in vitro. BIV-inoculated calves had significantly higher numbers of circulating lymphocytes, and follicular hyperplasia was observed in lymph nodes, hemal nodes, and spleen. The histopathological changes observed in BIV-infected calves were similar to changes found early after infection with the immunosuppressive lentiviruses, including human immunodeficiency virus type 1. PMID- 1309890 TI - Divergent envelope E2 alphavirus sequences spanning amino acids 297 to 352 induce in mice virus-specific protective immunity and antibodies with complement mediated cytolytic activity. AB - We have proposed a general algorithm for identification of potential immunoprotective domains (cassettes) on the envelope E2 polypeptide of alphaviruses (H. Grosfeld, B. Velan, M. Leitner, S. Cohen, S. Lustig, B.E. Lachmi, and A. Shafferman, J. Virol. 63:3416-3422, 1989). To assess the generality of our approach, we compared analogous E2 cassettes from Sindbis virus (SIN) and Semliki Forest virus (SFV), two alphaviruses which are philogenetically very remote. The antigenically distinct SFV E2 and SIN E2 cassettes exhibit comparable immunological characteristics. Most significantly, the SIN E2 LMN cassette cluster (E2 amino acids 297 to 352 fused to beta-galactosidase), like the analogous SFV E2 LMN cassettes, elicited high titers of antivirus antibodies in mice and proved to be highly effective in protection against lethal challenge. Mice immunized with SIN E2 LMN were completely protected against intracerebral challenge of 10 to 100 50% lethal doses of different neurovirulent SIN strains. Anti-SIN LMN antibodies, like anti-SFV LMN antibodies, lacked in vitro neutralizing activity, yet both exerted protection against homologous challenge upon transfer to mice. The two antibody preparations exhibited virus-specific complement-mediated cytolysis of cells infected with the homologous but not heterologous virus. These results suggest a possible mechanism for virus-specific E2 LMN-induced protection and demonstrate the generality of our methodology for deciphering immunogenic and protective domains in alphavirus systems. Results suggest also that the E2 LMN sequence of any given alphavirus should be considered as a component of a synthetic vaccine against that specific virus. PMID- 1309891 TI - Isolation and partial characterization of infectious molecular clones of feline immunodeficiency virus obtained directly from bone marrow DNA of a naturally infected cat. AB - Replication-competent molecular clones of feline immunodeficiency virus (FIV) were isolated directly from the DNA of bone marrow cells of a naturally FIV infected cat. After transfection in a feline kidney cell line (CrFK) and subsequent cocultivation with peripheral blood mononuclear cells (PBMC), the viral progeny of the clones was infectious for PBMC but not for CrFK cells. PBMC infected with these clones showed syncytium formation, a decrease in cell viability, and gradual loss of CD4+ cells. The restriction maps of these clones differed from those obtained for previously described molecular clones of FIV derived from cats in the United States. The predicted amino acid sequence similarity of the envelope genes of the two clones was 99.3%, whereas the similarities of the sequences of the clones to those of two molecular clones from the United States, Petaluma and PPR, were 86 and 88%, respectively. Most of the differences between the amino acid sequences of the two clones and those of the clones from the United States were found in five different hypervariable (HV) regions, HV-1 through HV-5. The viral progeny of one of these clones was inoculated into two specific-pathogen-free cats. The animals seroconverted, and the virus could be reisolated from their PBMC. PMID- 1309892 TI - Characterization of human cytomegalovirus UL84 early gene and identification of its putative protein product. AB - The DNA sequence and transcription pattern of human cytomegalovirus early gene UL84 were analyzed. This gene was mapped within a 2.6-kb PstI fragment located between 0.534 and 0.545 map unit of the large unique segment of the human cytomegalovirus genome, which is adjacent to the pp65 and pp71 genes. A 2.0-kb mRNA was transcribed from this region in the same leftward direction as the mRNAs of the pp65 and pp71 genes. The message was first detected at 2.5 h postinfection and reached a maximal level between 72 and 96 h postinfection. The nucleotide sequences of the 2.6-kb PstI genomic DNA fragment and the cDNA derived from this region were determined. The resulting data revealed a polyadenylation signal (AATAAA) located 14 nucleotides upstream from the poly(A) tail of the cDNA and a 1,761-bp open reading frame capable of encoding a 65-kDa polypeptide. A potential leucine zipper was found in the N-terminal half of the peptide molecule between amino acids 114 and 135. In addition, a different periodic leucine repeat with leucine at every eighth position was found between amino acids 325 and 373. The transcriptional initiation site of this early gene was determined by primer extension analysis. A putative TATA box (TATTTAA) located 24 bp upstream of the cap site and several inverted repeats were found in the region further upstream of the TATA box. To test whether the open reading frame of this cDNA encodes a virus-specific protein, the cDNA was overexpressed in Escherichia coli as a fusion protein used to generate antibodies in rabbits. A protein with a molecular size of 65 kDa was detected in the infected-cell extracts harvested at 6 to 72 h postinfection, but not in purified virions, using immunoblot analysis. Both nuclear and cytoplasmic fluorescences were found at late stages of virus infection. From the results obtained, we postulate that UL84 may be a stable, virus-specific, nonstructural protein capable of forming a homo- or heterodimeric molecule. PMID- 1309893 TI - Sequential phosphorylation of the phosphoprotein of vesicular stomatitis virus by cellular and viral protein kinases is essential for transcription activation. AB - The phosphoprotein (P) and the large protein (L) constitute the RNA-dependent RNA polymerase of vesicular stomatitis virus (VSV). We show that phosphate-free P protein expressed in bacteria is transcriptionally inactive when reconstituted with L protein and viral N-RNA template free of cellular protein kinase. Phosphorylation of P protein by a cellular kinase(s) was essential for transcription as well as for further phosphorylation by an L-associated kinase, the two kinases acting in a sequential (cascade) manner. Phosphate groups introduced by cell kinase were stable, whereas those due to L kinase underwent a turnover which was coupled to ongoing transcription. We present a model for the phosphorylation pathway of P protein and propose that continued phosphorylation and dephosphorylation of P protein may represent a transcriptional regulatory (on off) switch of nonsegmented negative-strand RNA viruses. PMID- 1309894 TI - Partial purification of adeno-associated virus Rep78, Rep52, and Rep40 and their biochemical characterization. AB - We have used differential cell extraction and conventional chromatography to separate and partially purify the four adeno-associated virus (AAV) nonstructural proteins Rep78, Rep68, Rep52, and Rep40. In the cytoplasmic extracts Rep52 and Rep40 were present in greater abundance than Rep68 and Rep78, with Rep78 being the least abundant. In nuclear extracts the four Rep proteins were approximately equal in abundance. Regardless of the subcellular fraction examined, three of the Rep proteins (Rep78, Rep68, and Rep40) consisted of two protein species with slightly different mobilities during polyacrylamide gel electrophoresis. In contrast, Rep52 consisted of only one protein species. Both Rep78 and Rep68 were capable of binding efficiently to AAV terminal hairpin DNA substrates, but we could not detect site-specific DNA binding by Rep52 and Rep40. Like Rep68, Rep78 had both an ATP-dependent trs endonuclease and a DNA helicase activity. Both Rep78 and Rep68 cut the terminal AAV sequence at the same site (nucleotide 124). The binding, trs endonuclease, and DNA helicase activities comigrated during sucrose density gradient centrifugation with a mobility expected for a monomer of the protein, suggesting that the three biochemical activities were intrinsic properties of the larger Rep proteins. The chromatographic behavior and the DNA binding properties of the four Rep proteins identified at least two domains within the rep coding region, an exposed hydrophobic domain within the C-terminal end (amino acids 578 to 621) and a region within the N terminus (amino acids 1 to 214) which was necessary for binding to the terminal repeat sequence. No site specific nuclease activity was seen in the presence of nucleotide analogs ATP gamma-S or AMP-PNP, suggesting that ATP hydrolysis was required for the endonuclease reaction. Furthermore, although ATP was the only cofactor which would support the trs endonuclease activity of Rep78, Rep68 nuclease activity was seen in the presence of several other nucleotide cofactors, including CTP, GTP, and UTP. PMID- 1309895 TI - Association between the herpes simplex virus major DNA-binding protein and alkaline nuclease. AB - Herpes simplex virus encodes seven proteins which have been shown to be both necessary and sufficient for in vitro replication of origin-containing plasmids. We have shown previously that one of these proteins, the major DNA-binding protein mDBP, forms a complex with alkaline nuclease, which is not one of the seven essential proteins. In this study, we have employed immunological reagents and a series of deletion mutants to investigate this complex further. We have determined the regions of mDBP which are important in the formation of this complex, and we have shown that the intranuclear locations of alkaline nuclease and major DNA-binding protein overlap. PMID- 1309896 TI - JC virus and simian virus 40 enhancers and transforming proteins: role in determining tissue specificity and pathogenicity in transgenic mice. AB - When introduced into the germ line of mice, the simian virus 40 (SV40) T antigen under the control of its own transcriptional enhancer and promoter selectively induced tumors in the choroid plexus as well as thymic hyperplasia and kidney pathology. In contrast, the JC virus (JCV) T antigen under the control of its own regulatory sequences induced hypomyelination of the central nervous system and tumors of neural origin. Since SV40 and JCV have extensive sequence homology, except for their transcriptional control regions, these observations suggest but do not prove that, although the diseases induced by the two viruses, are consequences of the transforming gene, they are determined predominantly by the respective viral enhancers and promoters. To test this hypothesis, the regulatory regions of the two viruses were exchanged, and transgenic mice were derived with either chimeric construct. Like wild-type JCV, the construct containing the SV40 T antigen under the control of the JCV regulatory region induced hypomyelination of the central nervous system and neural tumors. Surprisingly, mice with this construct also developed choroid plexus carcinomas. Like the wild-type SV40 transgenic mice, mice with the JCV T antigen under the control of the SV40 enhancer and promoter developed choroid plexus tumors and renal pathology. Unexpectedly, they also had hyperplasia of the thyroid follicular cells. These findings not only provide direct evidence for the specificity of the respective viral regulatory region but also, more importantly, show that the transforming genes play a critical role in determining viral pathogenesis. PMID- 1309897 TI - Finite life span of hybrids formed by fusion of different simian virus 40 immortalized human cell lines. AB - Simian virus 40 (SV40) genes are able to induce immortalization of normal human cells after a culture crisis during which unknown cellular genetic changes presumably occur. To determine whether these genetic changes are always identical, we performed somatic cell hybridization analysis of an SV40 immortalized human bronchial epithelial cell line, BET-1A. Fusion of BET-1A with an SV40-immortalized fibroblast cell line resulted in hybrids that senesced, indicating that these cell lines are in different complementation groups for immortalization. PMID- 1309898 TI - Feline leukemia virus subgroup B uses the same cell surface receptor as gibbon ape leukemia virus. AB - Pseudotypes of gibbon ape leukemia virus/simian sarcoma-associated virus (GALV/SSAV) and feline leukemia virus subgroup B (FeLV-B) have been constructed by rescuing a Moloney murine leukemia virus vector genome with wild-type GALV/SSAV or FeLV-B. The resulting recombinant viruses utilized core and envelope proteins from the wild-type virus and conferred resistance to growth in L histidinol upon infected cells by virtue of the HisD gene encoded by the vector genome. They displayed the host range specificity of the rescuing viruses and could be neutralized by virus-specific antisera. Receptor cross-interference was observed when the GALV/SSAV or FeLV-B pseudotypes were used to superinfect cells productively infected with either GALV/SSAV or FeLV-B. Although murine cells are resistant to FeLV-B infection, murine cells expressing the human gene for the GALV/SSAV receptor became susceptible to FeLV-B infection. Therefore GALV/SSAV and FeLV-B utilize the same cell surface receptor. PMID- 1309899 TI - Identification of cognate genes among heterologous strains of group B rotavirus. AB - The genetic relatedness of group B rotavirus (GBR) strains has previously been documented by hybridization with probes derived from whole genomic sequences, but the relationship of individual genes of heterologous GBR strains has not been evaluated. Definition of cognate GBR genes would facilitate investigation of the determinants of group specificity, serotype identity, and neutralization epitopes. Therefore, we investigated the genetic relatedness of three GBR strains by means of Northern (RNA) blot hybridization with isotopically labeled probes prepared from each of the 11 genes of the IDIR strain of GBR. Under low stringency conditions, hybridization between each of the IDIR gene probes and genomic RNA from the ADRV strain of GBR was observed. Genomic RNA obtained from a bovine strain of GBR hybridized with 9 of the 11 IDIR gene probes. In most cases, cognate genes of each of the GBR strains appeared to migrate to similar positions following polyacrylamide gel electrophoresis. However, the electropherotype positions of GBR genes 5, 6, and 7 were different for each of the three GBR strains. Identification of these genomic segments among GBR strains should prove helpful in future evaluations of GBR structure and function. PMID- 1309900 TI - In vitro resolution of adeno-associated virus DNA hairpin termini by wild-type Rep protein is inhibited by a dominant-negative mutant of rep. AB - An adeno-associated virus (AAV) genome with a Lys-to-His (K340H) mutation in the consensus nucleotide triphosphate binding site of the rep gene has a dominant negative DNA replication phenotype in vivo. We expressed both wild-type (Rep78) and mutant (Rep78NTP) proteins in two helper-free expression systems consisting of either recombinant baculoviruses in insect cells or the human immunodeficiency virus type 1 long terminal repeat promoter in human 293 cell transient transfections. We analyzed nuclear extracts from both expression systems for the ability to complement uninfected HeLa cell cytoplasmic extracts in an in vitro terminal resolution assay in which a covalently closed AAV terminal hairpin structure is converted to an extended linear duplex. Although both Rep78 and Rep78NTP bound to AAV terminal hairpin DNA in vitro, Rep78 but not Rep78NTP complemented the terminal resolution assay. Furthermore, Rep78NTP was trans dominant for AAV terminal resolution in vitro. We propose that the dominant negative replication phenotype of AAV genomes carrying the K340H mutation is mediated by mutant Rep proteins binding to the terminal repeat hairpin. PMID- 1309901 TI - Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigens. AB - Hepatitis delta virus (HDV) particles were produced in Huh7 human hepatoma cells by transfection with cloned hepatitis B virus (HBV) DNA and HDV cDNA. The particles were characterized by their buoyant density, the presence of encapsidated viral RNA, and their ability to infect primary cultures of chimpanzee hepatocytes. Successful infection was evidenced by the appearance of increasing amounts of intracellular HDV RNA after exposure to particles. Infection was prevented when particles were incubated with antibodies directed against synthetic peptides specific for epitopes of the pre-S1 or pre-S2 domains of the HBV envelope proteins before exposure to hepatocytes. These data demonstrate that HDV particles produced in vitro are infectious and indicate (i) that infectious particles are coated with HBV envelope proteins that contain the pre-S1 and pre-S2 regions, (ii) that epitopes of the pre-S1 and pre-S2 domains of HBV envelope proteins are exposed at the surface of HDV particles, and (iii) that antibodies directed against those epitopes have neutralizing activity against HDV. PMID- 1309902 TI - Induction of polyomavirus DNA replication by carcinogens in polyomavirus transformed rat cells: evidence that the viral enhancer is not the primary target in the induction pathway. AB - In the polyomavirus (Py)-transformed rat cell line designated LPT, replication of the integrated Py DNA can be induced by exposure of the cells to carcinogens. In view of the observation that enhancer elements are essential components of the Py origin of replication, it appeared plausible that the induction is triggered by synthesis or modification of an enhancer-binding protein which is required for activation of the viral origin. To test this hypothesis, we have used a plasmid containing a modified Py origin (test plasmid), in which the Py enhancer has been replaced with five repeats of the yeast GAL4 upstream activating sequence, and a plasmid encoding the GAL4 transcriptional activator protein. Previous studies in which these two plasmids were cotransfected into mouse cells that are permissive for Py showed that the GAL4 protein can transactivate the modified Py origin and cause replication of the test plasmid. When similar cotransfection assays were performed in LPT cells, no replication of the test plasmid was observed unless the cells were exposed to the carcinogen mitomycin C subsequent to the transfection, in which case replication of the test plasmid was induced. Control experiments showed that even though the GAL4 protein was required for the induction, its concentration was not affected by the exposure to mitomycin C. These results indicate that the primary target in the induction pathway is not an enhancer-binding protein; instead, the induction appears to be triggered by changes in other components of the replication initiation complex which may be associated with the origin core. PMID- 1309903 TI - v-mos proteins encoded by myeloproliferative sarcoma virus and its ts159 mutant. AB - The myeloproliferative sarcoma virus (MPSV) v-mos protein was predicted to be identical in size to p39c-mos because of an observed one-base deletion in the seventh codon of the env-mos open reading frame, which would allow translation to initiate at the methionine equivalent to codon 32 of the env-mos gene. On the basis of published results, p39c-mos is known to have greatly reduced in vitro protein kinase activity compared with p37env-mos encoded by Moloney murine sarcoma virus. Unexpectedly, the relative activity of the MPSV v-mos protein kinase was comparable to that of p37env-mos. Consistent with this finding, the size of MPSV v-mos protein was found to be similar to the size of p37env-mos. Moreover, the pattern and sizes of phosphorylated bands produced by autophosphorylation of the MPSV v-mos protein were similar to those of p37env mos. These results were confirmed by in vitro transcription-translation of the MPSV v-mos gene. Resequencing portions of the MPSV mos gene failed to show the deletion within codon 7. Except for the codon 262 deletion, other mutations characteristic of MPSV and temperature-sensitive MPSV v-mos genes were confirmed. A glycine-to-arginine mutation at residue 338 of the MPSV env-mos sequence, previously shown to cause thermosensitivity of the mutant virus (termed ts159) transforming function, yielded a v-mos protein that had significantly reduced protein kinase activity in vitro. These findings indicate that MPSV, like other Moloney murine sarcoma virus strains, also encodes a functional env-mos protein. PMID- 1309904 TI - Naturally occurring point mutation in the C terminus of the polymerase gene prevents duck hepatitis B virus RNA packaging. AB - A duck hepatitis B virus (DHBV) genome cloned from a domestic duck from the People's Republic of China has been sequenced and exhibits no variation in sequences known to be important in viral replication or generation of gene products. Intrahepatic transfection of a dimer of this viral genome into ducklings did not result in viremia or any sign of virus infection, indicating that the genome was defective. Functional analysis of this mutant genome, performed by transfecting the DNA into a chicken hepatoma cell line capable of replicating wild-type virus, indicated that viral RNA is not encapsidated. However, virus core protein is made and can assemble into particles in the absence of encapsidation of viral nucleic acid. Using genetic approaches, it was determined that a change of cysteine to tyrosine in position 711 in the polymerase (P) gene C terminus led to this RNA-packaging defect. By site-directed mutagenesis, it was found that while substitution of Cys-711 with tryptophan also abolished packaging, substitution with methionine did not affect packaging or viral replication. Therefore, Cys-711, which is conserved in all published sequences of DHBV, may not be involved in a disulfide bridge structure essential to viral RNA packaging or replication. Our results, showing that a missense mutation in the region of the DHBV polymerase protein thought to be primarily the RNase H domain results in packaging deficiency, support the previous findings that multiple regions of the complex hepadnaviral polymerase protein may be required for viral RNA packaging. PMID- 1309906 TI - Novel GACG-hairpin pair motif in the 5' untranslated region of type C retroviruses related to murine leukemia virus. AB - We searched for the presence of common RNA structural motifs in mammalian type C retroviruses related to murine leukemia viruses and the closely related avian spleen necrosis virus. A novel motif consisting of a pair of hairpins, called hairpin pair motif, was detected in the 5' untranslated regions of the genomes of these retroviruses. A combination of computational analyses that included the assessment of phylogenetic sequence conservation by multiple alignment, the search for regions with unusual RNA folding properties, and the analysis of RNA secondary structure by suboptimal free-energy calculations highlighted the significance of this hairpin pair motif. The hairpin pair motif encompasses 70 to 80 nucleotides between the splice donor site and the gag translational initiation codon of these viruses. The motif is composed of two adjacent hairpins both with a perfectly conserved GACG tetraloop. We propose that the novel GACG-hairpin pair motif described here constitutes an essential component of the regulatory machinery in these type C retroviruses. PMID- 1309905 TI - The ICP4 binding sites in the herpes simplex virus type 1 glycoprotein D (gD) promoter are not essential for efficient gD transcription during virus infection. AB - Activation of the early and late genes of herpes simplex virus type 1 during infection in tissue culture requires functional immediate-early regulatory protein ICP4. ICP4 is a specific DNA-binding protein which recognizes a variety of DNA sequences, many of which contain the consensus ATCGTC. In general, mutations which impair the ability of ICP4 to bind to DNA also eliminate its ability to activate viral early and late promoters both in transfection assays and in the infected cell. However, the role of ICP4 binding sites in the viral genome is unclear; many early and late promoters do not contain consensus binding sites in their vicinity. The glycoprotein D (gD) gene contains two well characterized ICP4 binding sites upstream of its promoter and a third downstream of the transcription start site. Multimerization of one of these sites has been shown to increase the response of the gD promoter to ICP4 in transfection assays, while their removal reduces stimulation of the gD promoter by ICP4 in vitro. To assess the role of these binding sites during virus infection, we have constructed a recombinant viral genome which has mutations affecting all three. Comparison of the amounts of gD RNA synthesized by the recombinant and wild-type viruses indicated that the mutations had little or no effect on the activity of the gD promoter. Therefore, either the sites have no essential role in gD promoter regulation in the presence of all of the herpes simplex virus type 1 IE polypeptides during a normal infection or they can be functionally substituted by other ICP4 binding sites elsewhere in the genome. PMID- 1309907 TI - Mutations in both the 2B and 2C genes of hepatitis A virus are involved in adaptation to growth in cell culture. AB - Oligonucleotide-directed mutagenesis of an infectious cDNA clone of wild-type hepatitis A virus was performed to determine which mutations acquired in the nonstructural 2B and 2C genes during adaptation to growth in cell culture were effective in enhancing virus growth in vitro. Results of transfection assays demonstrated that one mutation in the 2B gene and two mutations in the 2C gene were responsible for an increased efficiency in growth, but growth enhancement required the participation of at least two of the three mutations. PMID- 1309908 TI - Interaction of Epstein-Barr virus nuclear antigen 1 with the viral latent origin of replication. AB - The Epstein-Barr virus latent origin of replication (oriP) requires only one viral protein, the Epstein-Barr virus nuclear antigen 1 (EBNA-1), for activity. oriP consists of two spatially separated, essential sequence elements, regions I and II, both of which contain multiple EBNA-1-binding sites. Region II contains, or is close to, the site at which DNA synthesis initiates. The role of region I, a transcriptional enhancer in cells that express EBNA-1, in replication is not understood. To determine how the binding of EBNA-1 to sites in region II leads to the initiation of DNA synthesis and to investigate the role of region I, EBNA-1 has been overproduced in insect cells by using a baculovirus vector and purified to homogeneity, and the interaction of EBNA-1 with oriP has been examined. Footprinting experiments demonstrated that EBNA-1 binds to oriP in a sequence specific manner and bends or untwists the DNA at two symmetry-related sites in region II. Distortion of region I by EBNA-1 was not detected, suggesting that differences in the spacing of binding sites in regions I and II and resulting protein-protein interactions underlie differences in their biological properties. KMnO4 footprinting experiments did not reveal significant single-stranded structures in region II, suggesting that cellular proteins may recognize the EBNA -region II complex and unwind the DNA duplex. Region I did not quantitatively or qualitatively alter the interaction of EBNA-1 with region II. The contribution of an A + T-rich sequence in region II to replication was investigated by a mutational analysis. The results indicated that the overall A + T-rich nature of this sequence is not essential for replication of oriP-bearing plasmids. Nuclease protection experiments performed with these mutagenized plasmids provided additional evidence for protein-protein interactions in region II. PMID- 1309909 TI - Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus. AB - Transmissible gastroenteritis virus, an enteropathogenic coronavirus of swine, is a potent inducer of alpha interferon (IFN-alpha) both in vitro and in vivo. Previous studies have shown that virus-infected fixed cells or viral suspensions were able to induce an early and strong IFN-alpha synthesis by naive lymphocytes. Two monoclonal antibodies directed against the viral membrane glycoprotein M (29,000; formerly E1) were found to markedly inhibit virus-induced IFN production, thus assigning to M protein a potential effector role in this phenomenon (B. Charley and H. Laude, J. Virol. 62:8-11, 1988). The present report describes the selection and characterization of a collection of 125 mutant viruses which escaped complement-mediated neutralization by two IFN induction blocking anti-M protein monoclonal antibodies. Two of these mutants, designated H92 and dm49-4, were found to exhibit a markedly reduced interferogenic activity. IFN synthesis by lymphocytes incubated with purified suspensions of these mutants was 30- to 300-fold lower than that of the parental virus. The transcription of IFN-alpha genes following induction by each mutant was decreased proportionally, as evidenced by Northern (RNA) blot analysis. The sequence of the M gene of 20 complement-mediated neutralization-resistant mutants, including the 2 defective mutants, was determined by direct sequencing of genome RNA. Thirteen distinct amino acid changes were predicted, all located at positions 6 to 22 from the N terminus of the mature M protein and within the putative ectodomain of the molecule. Two substitutions, Thr-17 to Ile and Ser-19 to Pro, were assumed to generate the defective phenotypes of mutants dm49-4 and H92, respectively. The alteration of an Asn-Ser-Thr sequence in dm49-4 virus led to the synthesis of an M protein devoid of a glycan side chain, which suggests a possible involvement of this structure in IFN induction. Overall, these data supported the view that an interferogenic determinant resides in the N-terminal, exposed part of the molecule and provided further evidence for the direct role of M protein in the induction of IFN-alpha by transmissible gastroenteritis virus. The acronym VIP (viral interferogenic protein) is proposed as a designation for this particular class of proteins. PMID- 1309910 TI - A cyclic AMP-responsive DNA-binding protein (CREB2) is a cellular transactivator of the bovine leukemia virus long terminal repeat. AB - To gain insight into the cellular regulation of bovine leukemia virus (BLV) trans activation, a lambda-gt11 cDNA library was constructed with mRNA isolated from a BLV-induced tumor and the recombinant proteins were screened with an oligonucleotide corresponding to the tax activation-responsive element (TAR). Two clones (called TAR-binding protein) were isolated from 750,000 lambda-gt11 plaques. The binding specificity was confirmed by Southwestern (DNA-protein) and gel retardation assays. Nucleotide sequence analysis revealed that TAR-binding protein is very similar to the CREB2 protein. It contains a leucine zipper structure required for dimerization, a basic amino acid domain, and multiple potential phosphorylation sites. A vector expressing CREB2 was transfected into D17 osteosarcoma cells. In the absence of the tax transactivator, the CREB2 protein and the cyclic AMP-dependent protein kinase A activate the BLV long terminal repeat at a basal expression level: trans activation reached 10% of the values obtained in the presence of tax alone. These data demonstrate that CREB2 is a cellular factor able to induce BLV long terminal repeat expression in the absence of tax protein and could thus be involved in the early stages of viral infection. In addition, we observed that in vitro tax-induced trans activation can be activated or inhibited by CREB2 depending on the presence or absence of protein kinase A. These data suggest that the cyclic AMP pathway plays a role in the regulation of viral expression in BLV-infected animals. PMID- 1309911 TI - Influence of adeno-associated virus on adherence and growth properties of normal cells. AB - It has been shown previously that infection of newly established cell cultures from malignant human tumors with adeno-associated parvovirus type 2 or type 5 results in growth arrest and cell death. Here we report that the additionally observed antiproliferative effect on diploid human fibroblasts is transient and is connected to a reduced number of cells in S phase. Progression through the cell cycle is disturbed either in G0/G1 or at the G1/S boundary, but an additional arrest in G2 cannot be excluded. DNA synthesis and cell proliferation are resumed when cells are recultured after loosening of cell-matrix adhesions by trypsin treatment. In contrast, they are not resumed by solely providing growth factors via higher amounts of fetal calf serum. The results suggest that cell adherence is altered in adeno-associated parvovirus-infected human embryo fibroblasts. PMID- 1309912 TI - Second-site homologous recombination in Epstein-Barr virus: insertion of type 1 EBNA 3 genes in place of type 2 has no effect on in vitro infection. AB - This study was undertaken to develop a general strategy for the introduction of mutations into specific sites in the Epstein-Barr virus (EBV) genome. Previous approaches were limited by the need for physical linkage of the transfected EBV DNA fragment to a positive selection marker. In our experiments, a positive selection marker was introduced into one site in the EBV genome and a distant, nonlinked, marker was introduced into another site. Each marker was on a large EBV DNA fragment and was inserted into the genome by transfection into cells carrying a resident EBV genome. The resident EBV genome was simultaneously induced to replicate by using a cotransfected expression plasmid for the EBV immediate-early transactivator, Z (J. Countryman, H. Jenson, R. Seibl, H. Wolf, and G. Miller, J. Virol. 61:3672-3679, 1987; G. Miller, M. Rabson, and L. Heston, J. Virol. 50:174-182, 1984). Eleven percent of the resultant EBV genomes which incorporated the positive selection marker also incorporated the nonlinked marker. Both markers uniformly targeted the homologous EBV genome site. In this way novel EBV recombinants were constructed in which the EBV type 1 EBNA 3A, EBV type 1 EBNA 3A and 3B, or EBV type 1 EBNA 3A, 3B, and 3C genes were introduced into a largely type 2 EBV genome, replacing the corresponding type 2 gene(s). No difference was observed in primary B-lymphocyte growth transformation, in latent EBV gene expression, or in spontaneous lytic EBV gene expression. These new recombinants should be useful for ongoing analyses of the type specificity of the immune response. PMID- 1309913 TI - Alterations to influenza virus hemagglutinin cytoplasmic tail modulate virus infectivity. AB - The influenza virus hemagglutinin (HA) contains a cytoplasmic domain that consists of 10 to 11 amino acids, of which five residues have sequence identity for 10 of 13 HA subtypes. To investigate properties of these conserved residues, oligonucleotide-directed mutagenesis was performed, using an HA cDNA of influenza virus A/Udorn/72 (H3N2) to substitute the conserved cysteine residues with other residues, to delete the three C-terminal conserved residues, or to remove the entire cytoplasmic domain. The altered HAs were expressed in eukaryotic cells, and the rates of intracellular transport were examined. It was found that substitution of either conserved cysteine residue within the cytoplasmic domain did not affect the rate of intracellular transport, whereas deletion of residues within the C-terminal domain resulted in delayed cell surface expression. All the altered HAs were biologically active in hemadsorption and fusion assays. To investigate whether the wild-type HA and HAs with altered cytoplasmic tails could complement the influenza virus temperature-sensitive transport-defective HA mutant A/WSN/33 ts61S, the HA cDNAs were expressed by using a transient expression system and released virus was assayed by plaque analysis. The wild type HA expression resulted in a release of approximately 10(3) PFU of virus per ml. Antibody neutralization of complemented virus indicated that the infectivity was due to incorporation of wild-type H3 HA into ts61S virions. Sucrose density gradient analysis of released virions showed that each of the HA cytoplasmic domain mutants was incorporated into virus particles. Virions containing HAs with substitution of the cysteine residues in the cytoplasmic domain were found to be infectious. However, no infectivity could be detected from virions containing HAs that had deletions in their cytoplasmic domains. Possible roles of the HA cytoplasmic domain in forming protein-protein interactions in virions and their involvement in the initiation of the infection process in cells are discussed. PMID- 1309914 TI - Simian virus 40 T-antigen DNA helicase is a hexamer which forms a binary complex during bidirectional unwinding from the viral origin of DNA replication. AB - The role of simian virus 40 (SV40) large tumor antigen (T antigen) as a DNA helicase at the replication fork was studied. We found that a T-antigen hexamer complex acts during the unidirectional unwinding of appropriate DNA substrates and is localized directly in the center of the fork, contacting the adjacent double strand as well as the emerging single strands. When bidirectional DNA unwinding, initiated at the viral origin of DNA replication, was analyzed, a larger T-antigen complex that is simultaneously active at both branch points of an unwinding bubble was observed. The size and shape of this helicase complex imply that the T-antigen dodecamer complex, assembled at the origin and active in the localized melting of duplex DNA, is subsequently also used to continue DNA unwinding bidirectionally. Then, however, the dodecamer complex does not split into two hexamer subunits that track along the DNA; rather, the DNA is threaded through the intact complex, with the concomitant extrusion of single-stranded loops. PMID- 1309915 TI - Human papillomavirus type 1 E4 proteins differing by their N-terminal ends have distinct cellular localizations when transiently expressed in vitro. AB - Two major human papillomavirus type 1 (HPV-1) E4 proteins are found in large amounts in productively infected differentiating wart cells, a 17-kDa protein translated from an E1-E4 transcript and a processed 16-kDa protein lacking the E1 amino acids at least. The functions of the E4 proteins are still unknown. We have designed an in vitro system allowing the transient expression of three forms of HPV-1 E4 proteins: the 17-kDa E1-E4 protein, an E4 protein without the five E1 amino acids (E4-3200), and E4 protein initiated at the E4 ATG located upstream of the splice acceptor site (E4-3181). The E4-3181 protein has five additional N terminal amino acids compared with E4-3200. The E4-3181 protein has not yet been detected in vivo but could, in principle, be translated from any transcript encoding the E2 protein. The constructs were transfected in two keratinocyte lines, one derived from a rabbit transplantable carcinoma (VX2R) and the other from a human penile carcinoma (SK-p). E4 transcripts with the expected size were detected in both cell lines by Northern (RNA) blot analysis. Surprisingly, the E4 proteins were found only in the VX2R cells by radioimmunoprecipitation and immunofluorescence experiments. The E1-E4 and the E4-3200 proteins were both cytoplasmic and were associated with granules reminiscent of the cytoplasmic inclusions pathognomonic of the HPV-1 infection. Moreover, each protein showed a specific staining pattern of the inclusions. In contrast, the E4-3181 protein was essentially intranuclear and perinuclear. Thus, HPV-1 E4 proteins differing in their N-terminal ends have distinct cellular localizations and arrangements. It is tempting to assume that this may relate to different roles. PMID- 1309916 TI - Herpes simplex virus infection can occur without involvement of the fibroblast growth factor receptor. AB - Basic fibroblast growth factor (bFGF) has been reported to block uptake of herpes simplex virus type 1 (HSV-1) and plaque formation on arterial smooth muscle cells, suggesting a role for the bFGF receptor in HSV entry (R. J. Kaner, A. Baird, A. Mansukhani, C. Basilico, B. D. Summers, R. Z. Florkiewicz, and D. P. Hajjar, Science 248:1410-1413, 1990). We confirmed the effect of bFGF on infection of this cell type with HSV-1 and HSV-2 and found the same result with umbilical vein endothelial cells. However, bFGF does not inhibit plaque formation on any other cell type we tested. Furthermore, there is no correlation between the level of expression of the bFGF receptor and the effect of bFGF. HEp-2 and A431 cells express barely detectable levels of receptor, and yet they are fully permissive for HSV infection in a bFGF-insensitive manner. Thus, interaction of virus with the bFGF receptor is not required for infection of many cell types. In addition, infection of smooth muscle cells is not prevented by incubation of virus with an anti-bFGF antibody, arguing against the hypothesis that virion associated bFGF acts as a bridge between virus and receptor (A. Baird, R. Z. Florkiewicz, P. A. Maher, R. J. Kaner, and D. P. Hajjar, Nature [London] 348:344 346, 1990). PMID- 1309917 TI - Glycoprotein IV of bovine herpesvirus 1-expressing cell line complements and rescues a conditionally lethal viral mutant. AB - Glycoprotein IV (gIV) of bovine herpesvirus 1 (BHV-1), a homolog of herpes simplex virus glycoprotein D, represents a major component of the viral envelope and a dominant immunogen. To analyze the functional role of gIV during BHV-1 replication, cell line BUIV3-7, which constitutively expresses gIV, was constructed and used for the isolation of gIV- BHV-1 mutant 80-221, in which the gIV gene was replaced by a lacZ expression cassette. On complementing gIV expressing cells, the gIV- BHV-1 replicated normally but was unable to form plaques and infectious progeny on noncomplementing cells. Further analysis showed that gIV is essential for BHV-1 entry into target cells, whereas viral gene expression, DNA replication, and envelopment appear unchanged in both noncomplementing and complementing cells infected with phenotypically complemented gIV- BHV-1. The block in entry could be overcome by polyethylene glycol-induced membrane fusion. After passaging of gIV- BHV-1 on complementing cells, a rescued variant, BHV-1res, was isolated and shown to underexpress gIV in comparison with its wild-type parent. Comparison of the penetration kinetics of BHV-1 wild type, phenotypically complemented gIV- BHV-1, and BHV-1res indicated that penetration efficiency correlated with the amount of gIV present in virus particles. In conclusion, we show that gIV of BHV-1 is an essential component of the virion involved in virus entry and that the amount of gIV in the viral envelope modulates the penetration efficiency of the virus. PMID- 1309918 TI - Utilization of heterologous alphavirus junction sequences as promoters by Sindbis virus. AB - We used Sindbis virus, an alphavirus, as a model to study the evolution of the recognition of viral cis-acting sequences. During the life cycle of alphaviruses, a full-length minus-strand RNA is made and serves as a template for both genomic RNA replication and subgenomic mRNA transcription. Transcription initiates at an internal promoter site, the junction sequence, to produce a subgenomic mRNA. The junction sequences of alphaviruses are highly conserved, but they do contain a number of base differences. These could have been essentially neutral mutations during evolution, such that any of the contemporary sequences can be recognized efficiently by any of the alphaviruses. Alternately, the changes could have resulted in significant functional divergence, such that the contemporary viruses can no longer recognize heterologous junction sequences as promoters. To distinguish between these possibilities, we constructed Sindbis virus derivatives with two subgenomic mRNA promoters. One is the wild-type Sindbis virus promoter used for expression of the structural proteins. The other is either the minimal Sindbis virus promoter or the corresponding junction sequences from other alphaviruses, which are placed upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene. RNA analyses were used to determine the relative promoter strengths of the various junction sequences. The results showed that all but two were recognized as promoters by Sindbis virus. CAT enzyme assays were used to measure the accumulation of CAT protein made from mRNAs transcribed by using the heterologous junction sequences as promoters. Most of the viruses expressed amounts of CAT enzyme within 10-fold of each other. The two viruses with junction sequences that were not recognized as promoters did not give significant CAT expression. We conclude that, with respect to Sindbis virus, the junction sequences are functionally conserved; i.e., most of the contemporary nucleotide differences in the junction sequences are neutral or near-neutral mutations. The functional conservation suggests that neither the cis-acting sequence nor the cognate binding site of the transcription factor can change independently. This type of coupled evolution between cis-acting sequences and their cognate viral protein binding sites may be a general phenomenon. For example, it explains the ubiquitous presence of conserved cis-acting sequences in each of the families of RNA viruses. There are implications of this hypothesis for the design of antiviral drugs. PMID- 1309919 TI - Pseudorabies virus envelope glycoproteins gp50 and gII are essential for virus penetration, but only gII is involved in membrane fusion. AB - To investigate the function of the envelope glycoproteins gp50 and gII of pseudorabies virus in the entry of the virus into cells, we used linker insertion mutagenesis to construct mutant viruses that are unable to express these proteins. In contrast to gD mutants of herpes simplex virus, gp50 mutants, isolated from complementing cells, were able to form plaques on noncomplementing cells. However, progeny virus released from these cells was noninfectious, although the virus was able to adsorb to cells. Thus, the virus requires gp50 to penetrate cells but does not require it in order to spread by cell fusion. This finding indicates that fusion of the virus envelope with the cell membrane is not identical to fusion of the cell membranes of infected and uninfected cells. In contrast to the gp50 mutants, the gII mutant was unable to produce plaques on noncomplementing cells. Examination by electron microscopy of cells infected by the gII mutant revealed that enveloped virus particles accumulated between the inner and outer nuclear membranes. Few noninfectious virus particles were released from the cell, and infected cells did not fuse with uninfected cells. These observations indicate that gII is involved in several membrane fusion events, such as (i) fusion of the viral envelope with the cell membrane during penetration, (ii) fusion of enveloped virus particles with the outer nuclear membrane during the release of nucleocapsids into the cytoplasm, and (iii) fusion of the cell membranes of infected and uninfected cells. PMID- 1309920 TI - Characterization of the Epstein-Barr virus BZLF1 protein transactivation domain. AB - Initiation of the Epstein-Barr virus (EBV) lytic cycle is dependent on expression of the viral transactivator Zta, which is encoded by the BZLF1 gene. Described here is an initial mapping of the regions of Zta involved in activating transcription. The data indicate that the amino-terminal 153 amino acids of Zta are important for activity, and in particular the region from residues 28 to 78 appears to be critical for Zta function. However, other features of Zta may be important for activity since a Gal4-Zta chimeric protein, generated by fusing the amino-terminal 167 residues of Zta to the DNA binding domain of the yeast transactivator Gal4, transactivated a minimal promoter containing one upstream Gal4 binding site but was unable to exhibit synergistic transactivation when assayed with a reporter containing five upstream Gal4 binding sites. PMID- 1309922 TI - Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages. AB - Antibody-dependent enhancement of virus infection is a process whereby virus antibody complexes initiate infection of cells via Fc receptor-mediated endocytosis. We sought to investigate antibody-dependent enhancement of feline infectious peritonitis virus infection of primary feline peritoneal macrophages in vitro. Enhancement of infection was assessed, after indirect immunofluorescent antibody labelling of infected cells, by determining the ratio between the number of cells infected in the presence and absence of virus-specific antibody. Infection enhancement was initially demonstrated by using heat-inactivated, virus specific feline antiserum. Functional compatibility between murine immunoglobulin molecules and feline Fc receptors was demonstrated by using murine anti-sheep erythrocyte serum and an antibody-coated sheep erythrocyte phagocytosis assay. Thirty-seven murine monoclonal antibodies specific for the nucleocapsid, membrane, or spike proteins of feline infectious peritonitis virus or transmissible gastroenteritis virus were assayed for their ability to enhance the infectivity of feline infectious peritonitis virus. Infection enhancement was mediated by a subset of spike protein-specific monoclonal antibodies. A distinct correlation was seen between the ability of a monoclonal antibody to cause virus neutralization in a routine cell culture neutralization assay and its ability to mediate infection enhancement of macrophages. Infection enhancement was shown to be Fc receptor mediated by blockade of antibody-Fc receptor interaction using staphylococcal protein A. Our results are consistent with the hypothesis that antibody-dependent enhancement of feline infectious peritonitis virus infectivity is mediated by antibody directed against specific sites on the spike protein. PMID- 1309921 TI - Characterization of the regulatory functions of the equine herpesvirus 1 immediate-early gene product. AB - Use of the translation-inhibiting drug cycloheximide has indicated that the equine herpesvirus 1 (EHV-1) immediate-early (IE) gene, the sole EHV-1 IE gene, encodes a major viral regulatory protein since IE mRNA translation is a prerequisite for all further viral gene expression (W.L. Gray, R. P. Baumann, A. T. Robertson, G. B. Caughman, D. J. O'Callaghan, and J. Staczek, Virology 158:79 87, 1987). An EHV-1 IE gene expression vector (pSVIE) in combination with chimeric EHV-1 promoter-chloramphenicol acetyltransferase (CAT) reporter constructs was used in transient transfection assays to characterize the regulatory functions of the IE gene product. These experiments demonstrated that (i) the EHV-1 IE gene product is a bifunctional protein capable of both positive and negative modulation of gene expression; (ii) the IE gene product possesses an autoregulatory function which represses the IE promoter; (iii) IE autoregulation is dependent on IE promoter sequences mapping within positions -288 to +73 relative to the transcription initiation site (+1) of the IE gene; (iv) the IE gene product can independently activate the EHV-1 tk promoter (an early promoter) by as much as 60-fold; (v) two EHV-1 beta-gamma (leaky late) promoters, those of IR5 (gene 5 in the inverted repeat) and the glycoprotein D gene, demonstrate a requirement for both the IE gene product as well as a gene product encoded within the EHV-1 XbaI G fragment for significant activation; and (vi) the IE gene product is capable of activating heterologous viral promoters. PMID- 1309923 TI - RNA sequence variants in live poliovirus vaccine and their relation to neurovirulence. AB - Mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC) was used to study sequence heterogeneity and stability in attenuated poliovirus type 3 at positions in which the vaccine virus differs from its wild type progenitor. Of seven genomic positions tested, only two (positions 472 and 2493) show nucleotide heterogeneity. Propagation of the vaccine virus in cell cultures leads to rapid selection of virus with reversions at these two positions of the genome. The relative abundance of reversions at position 472 correlates with the results of monkey neurovirulence tests, while the mutation at position 2493 is not directly associated with neurovirulence of the virus in monkeys. Instead, the abundance of mutations at the latter position correlates with the source of the seed virus and its passage level. These results further indicate that MAPREC at position 472 can be used to assess the quality of poliovirus type 3 vaccine. PMID- 1309925 TI - Viral myocarditis--a tale of two diseases. PMID- 1309924 TI - Hepatitis B virus X protein activates transcription factor NF-kappa B without a requirement for protein kinase C. AB - The hepatitis B virus X protein stimulates transcription from a variety of promoter elements, including those activated by transcription factor NF-kappa B. A diverse group of extra- and intracellular agents, including growth factors and the human immunodeficiency virus tat protein, have been shown to require a functional protein kinase C (PKC) system to achieve activation of NF-kappa B. In this study we have investigated the molecular mechanism by which X protein activates NF-kappa B. We demonstrate that in hepatocytes, X protein induces a maximal activation of NF-kappa B corresponding to the sequestered pool of factor, which is also activated by phorbol esters. To determine whether X protein requires activation of PKC to stimulate transcription by NF-kappa B, we attempted to prevent transactivation by X protein in the presence of the PKC inhibitors calphostin C and H7. We show that PKC inhibitors do not block X protein activation of NF-kappa B, whereas they largely impair activation by phorbol esters. In addition, activation of PKC is correlated with its translocation from the cytoplasm to the plasma membrane. The subcellular distribution of PKC was investigated by introducing X protein from a replication-defective adenovirus vector, followed by immunochemical detection of PKC in cell fractions. These data also indicate that X protein stimulates transcription by NF-kappa B without the activation and translocation of PKC. PMID- 1309926 TI - Platelet-derived growth factor receptor (beta-subunit) immunoreactivity in soft tissue tumors. AB - Using a well characterized monoclonal antibody (PR7212) to the beta-subunit of the platelet-derived growth factor receptor (PDGF-R(beta) and the avidin-biotin peroxidase method on frozen sections, we analyzed PDGF-R(beta) expression in 71 nonepithelial lesions as well as normal mesenchymal tissues. PDGF-R(beta) reactivity was observed in normal salivary gland, normal cutaneous and visceral fibroblasts, muscularis mucosa of bowel, and endothelial cells; squamous carcinoma was negative. Interestingly, hepatocytes and lymph node histiocytes were also positive. Positive tumors included malignant fibrous histiocytoma (6/6), benign and malignant smooth muscle tumors (5/6 leiomyoma, 8/9 leiomyosarcoma), liposarcoma (4/4), synovial sarcoma (6/7), angiosarcoma (2/2), and sarcoma NOS (2/2). Fibromatosis cases were also positive (2/2). In many tumors, the reactive fibroblasts and vascular components were also reactive. The characteristic pattern of reactivity in fibroblastic lesions highlighted thin cytoplasmic extensions or strands not visible in normal hematoxylin and eosin stained sections. Expression of PDGF-R(beta) was not necessarily correlated with the presence of PDGF. We conclude that PDGF-R(beta) expression can be identified in a wide variety of mesenchymal lesions and postulate that its presence may be important in the mechanism of growth of these tumors. PMID- 1309927 TI - Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury. AB - Inbred mice with genetically determined severe combined immunodeficiency (SCID) lack mature T and B lymphocyte functions. To distinguish direct viral effects in the pathogenesis of myocarditis from those mediated by antigen-specific and histocompatibility-complex-restricted host immunity, we inoculated coxsackievirus B3 into homozygous young adult SCID mice. We found that infected SCID mice invariably developed extensive myocarditis between 7 and 14 days postinoculation with high subsequent mortality. Histopathologic examination of the infected SCID myocardium indicated multiple foci of cardiomyocyte necrosis and a delayed pleomorphic inflammatory infiltrate. Immunohistochemically, the coxsackievirus B3 infected SCID heart contained frequent clusters of macrophages (Mac-1+) as well as other cells that may represent nonspecific phagocytic or cytolytic effectors. In situ hybridization with radiolabeled cDNA probes for enteroviral genome indicated a significant excess of positive-strand genome in the SCID myocardium compared with that in similarly infected non-SCID controls, with hybridization signals localized primarily to cardiomyocytes. In vitro culture confirmed persistent viremia and a vast excess of infective virus in the SCID myocardium relative to infected non-SCID controls. Thus, direct viral mechanisms in the production of cardiomyocyte injury in coxsackievirus B3-infected mice appear to be more important than previously recognized, particularly in the setting of unrestricted viral proliferation. PMID- 1309928 TI - Herpes simplex virus type 1 replicates in the lens and induces cataracts in mice. AB - In a mouse model, cataracts were produced after corneal inoculation with herpes simplex virus type 1 (HSV-1) strain F. Viral antigen was detected in vivo by the immunoperoxidase technique in lens fibers and occasionally in lens epithelial cell nuclei at 4 and 5 days postinoculation. HSV-1 replication within the lens was further demonstrated by virus isolation from lenses that had been inoculated in vitro. Lens lesions in mice were present as early as 4 days postinoculation and by later times (23 to 60 days postinoculation), severe degenerative changes typical of cataracts were present in many of the lenses examined histologically. Viral DNA was detected in extracts of lenses from infected animals at 5 and 11 days postinoculation. In contrast to HSV-1 F, the KOS strain of HSV-1 produced intraocular infection and cataracts at a much lower frequency in mice. Lens lesions appear to be induced directly by viral replication within the lens; however, other mechanisms involving inflammation in adjacent eye structures may also be involved in the pathogenesis of these lesions. Based upon these data, it is reasonable to consider the possibility that HSV-1 may be involved in the production of cataracts in humans in some cases. PMID- 1309930 TI - Peripheral neuropathy induced by 2',3'-dideoxycytidine. A rabbit model of 2',3' dideoxycytidine neurotoxicity. AB - The nucleoside analog 2',3'-dideoxycytidine (ddC) is a potent inhibitor of the reverse transcriptase of human immunodeficiency virus and a DNA chain terminator. In clinical trials in patients with acquired immunodeficiency syndrome, ddC treatment has been associated with a dose-limiting and dose-dependent, painful, sensorimotor peripheral neuropathy. In search of an animal model for ddC-induced neurotoxicity we studied 36 New Zealand White rabbits (3 males/3 females/group) given 0, 10, 50, 100, 150, or 250 mg/kg/day of ddC, by oral intubation, for 13 or 18 weeks. Rabbits in the 150 and 250 mg/kg/day groups were sacrificed at 13 weeks because of hematopoietic toxicity. After 16 weeks, rabbits in the 50 and 100 mg/kg/day groups showed hindlimb paresis and/or gait abnormalities. Nerve conduction velocities and amplitudes in the 100 mg/kg/day rabbits were reduced by 30 to 50%. The most prominent pathologic changes in peripheral nerve and ventral roots of ddC-treated rabbits were (a) myelin splitting and intramyelinic edema, (b) demyelination and remyelination of axons, and (c) axonal loss. Treatment related histologic lesions were not observed in spinal cord, brain, or retina. The pathology in these ddC-treated rabbits is consistent with a peripheral myelinopathy and axonopathy. This represents the first clinical, electrophysiologic, and pathologic description of an animal model of a peripheral neuropathy induced by a nucleoside analog. PMID- 1309929 TI - Transgenic mice expressing polyoma virus large T antigen in astrocytes develop severe dysmyelination of the central nervous system. AB - Transgenic mice were generated using a construct that encodes mouse polyoma virus large T antigen, one of three oncogenic products of the "early region" of the polyoma viral genome. Of 16 transgenic families developed, 1 was characterized by a neurologic disorder consisting of constant tremor and recurrent seizures. Morphologic analysis of the central nervous system (CNS) of affected transgenic mice included: classical light and electron microscopic examination; immunohistochemical assessment of the presence and localization of myelin specific proteins, of the astrocyte marker glial fibrillary acidic protein, of the oligodendrocyte marker galactosyl cerebroside, and of large T; double immunolabeling of glial fibrillary acidic protein or galactosyl cerebroside and large T to identify the CNS cell type in which large T is expressed; and in situ hybridization to study myelin basic protein gene expression. Our results suggest that polyoma large T is expressed in astrocytes, possibly resulting in altered glial-glial interactions causing impaired oligodendroglial development and secondary dysmyelination. Transgenic oligodendrocytes exhibit features of immaturity, failing to myelinate axons properly and producing morphologic phenotypes of early stages of myelination, such as numerous mesaxonal profiles. Myelin proteins are markedly reduced in transgenic CNS, and myelin basic protein transcripts, while present, are generally decreased. We believe that expression of large T in astrocytes could influence the complex and dynamic interactions between astrocytes and oligodendrocytes, perhaps with regard to the molecular (trophic) signals in the local CNS environment, bringing about arrested oligodendroglial maturation and hypomyelination. This raises intriguing questions concerning the importance of glial-glial interactions in the CNS and the complex levels of control involved in biological expression of genetic information in glial cells. PMID- 1309931 TI - Ultrastructure of peripheral neuropathy induced in rabbits by 2',3' dideoxycytidine. AB - The nucleoside analogue, 2',3'-dideoxycytidine (ddC), an inhibitor of human immunodeficiency virus reverse transcriptase, mediates virologic and immunologic improvements in acquired immunodeficiency syndrome patients. However, in clinical studies ddC treatment is associated with a dose-limiting peripheral neuropathy. The purpose of this study was to characterize the ultrastructural features of the peripheral neuropathy induced in rabbits. Rabbits received 0, 10, 50, or 100 mg/kg/day of ddC for 18 weeks. A prominent ultrastructural change induced by ddC in sciatic nerve and ventral root was separation of myelin lamellae at the intraperiod line and vacuolation and fragmentation of myelin sheaths. Many demyelinated and remyelinated axons were observed. Although pathologic alterations in Schwann cells were evident by the presence of lipid droplets and myelin figures, their formation was not considered a primary event. Axons containing abnormal cytoplasmic components were occasionally observed. Other changes included redundance of Schwann cell basal lamina and the presence of lipid droplets and/or myelin figures within endoneurial fibroblasts and macrophages. The results of this study indicate that ddC induces a myelinopathy in rabbits characterized by myelin splitting and intramyelinic edema and an axonopathy that may be secondary to the myelin changes. PMID- 1309932 TI - A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. AB - The clinical triad of a firstborn delivered vaginally to a young (teenage) mother has been previously noted among juvenile onset recurrent respiratory papillomatosis (JO-RRP) patients. This study was based on a questionnaire survey of JO-RRP patients, adult onset recurrent respiratory papillomatosis (AO-RRP) patients, and juvenile and adult controls. The survey results revealed that the complete or partial triad was observed in 72% of JO-RRP patients, 36% of AO-RRP patients, 29% of juvenile controls, and 38% of adult controls. As compared with juvenile controls, JO-RRP patients were more often firstborn (P less than .05), delivered vaginally (P less than .05), and born to a teenage mother (P less than .01). Among adult participants, AO-RRP patients reported more lifetime sex partners (P less than .01) and a higher frequency of oral sex (P less than .05) than reported by adult controls. AO-RRP and JO-RRP appear to have distinguishable epidemiologic features indicating that the mode of human papillomavirus (HPV) transmission is different in these two disorders. PMID- 1309933 TI - Evidence for antagonistic activity of endothelin for clonidine induced hypotension and bradycardia. AB - Effect of endothelin (ET) on clonidine induced cardiovascular effects was studied in male Sprague-Dawley rats. Clonidine (75 micrograms/kg, iv) produced significant decrease in blood pressure and heart rate. ET-1 (50 ng/kg, iv) pretreatment completely antagonized the hypotension and bradycardia induced by clonidine. ET-2 (50 ng/kg, iv) and ET-3 (50 ng/kg, iv) had similar antagonistic effect on clonidine induced hypotension and bradycardia. The antagonistic effect of ET lasted for several hours, however, 4 hours after ET pretreatment only partial blockade of clonidine induced hypotension and bradycardia was observed. This indicated that the antagonistic effect of ET was reversible. Initial hypertensive response induced by high dose of clonidine (750 micrograms/kg, iv) could not be antagonized by ET-1, ET-2 or ET-3, while phenoxybenzamine, an alpha adrenoceptor antagonist, blocked the hypertensive response of clonidine. Thus, ET has no antagonistic effect on the initial hypertensive response but antagonizes the hypotensive and bradycardic effect induced by clonidine. Clonidine induced hypotension and bradycardia are mediated through central alpha 2 adrenoceptors while hypertension is mediated through peripheral alpha 2 adrenoceptors. It is concluded that central alpha 2 adrenoceptors are different from peripheral alpha 2 adrenoceptors and ET antagonizes the effect of clonidine only on central alpha 2 adrenoceptors but has no antagonistic activity on peripheral alpha 2 adrenoceptors. PMID- 1309934 TI - Properties and functions of human placental opioid system. AB - Human placental villus tissue contains opioid receptors and peptides. Kappa opioid receptors (the only type present in this tissue) were purified with retention of their binding properties. The purified kappa receptor is a glycoprotein with an apparent molecular weight of 63,000. Two opioid receptor mediated functions were identified in trophoblast tissue, namely regulation of acetylcholine and hormonal (human chorionic gonadotrophin and human placental lactogen) release. Placental content of kappa receptors increases with gestational age. Term placental content of kappa receptors correlates with route of delivery (higher in those abdominally obtained). Opioid use and/or abuse during pregnancy affects placental receptor content at delivery, as well as its mediated functions. Opioid peptides identified in placental extracts were beta endorphin, methionine enkephalin, leucine enkephalin and dynorphins 1-8 and 1-13. Dynorphin 1-8 seem to be the predominant opioid peptide present in placental villus tissue. PMID- 1309935 TI - Simultaneous effects of the platelet 5-HT2 and alpha 2-adrenergic receptor populations on phosphoinositide hydrolysis. AB - The interaction of multiple receptor populations on a common second messenger system is a critical aspect of cell function and may be involved in pathology. We studied the interactions of the 5-HT2, alpha 2-adrenergic and prostaglandin (PGI2) receptors on phosphoinositide (PI) turnover in human platelets. Serotonin and epinephrine (EPI) stimulated PI hydrolysis in a dose-dependent manner. The PI turnover response to serotonin was mediated by the 5-HT2 receptor. The PI response to EPI was mediated by alpha 2-adrenergic receptors. An additive PI turnover response was generated by the combination of 5-HT and EPI. The sum of the maximal responses to 5-HT (72.5 +/- 4.9%) and EPI (56.0 +/- 4.2%) approximated the maximal response (129.3 +/- 9.5) to the combination. Prostacyclin (PGI2) at 1 microgram/mL reduced PI turnover by 21.8 +/- 1.1%. The PI response to 5-HT and EPI was not significantly altered once the reduction in the baseline PI turnover by PGI2 is taken into account. Similarly, PGI2 did not reduce PI hydrolysis stimulated by a combination of 5-HT (0.2 mM) and EPI (0.1 mM) once the decrease in baseline was taken into account (p greater than 0.20). The summation of serotonin stimulation of PI turnover by a combination of both epinephrine and serotonin was blocked by either yohimbine or ketanserin. These studies indicate: (1) the pool of phospholipases appears to exceed the maximal capacity of the individual alpha 2-adrenergic and 5-HT2 receptor populations to activate this second messenger system. (2) inhibition of serotonin or epinephrine stimulated PI turnover by prostacyclin is due to a lowering of basal PI turnover. Future studies should examine other cell systems to assess the generalizability of these findings regarding the differences in effects on a second messenger system when activated by one receptor population as opposed to two different receptor types. PMID- 1309936 TI - Non-isopeptide-selective endothelin receptors in human Girardi heart cells. AB - We characterized the endothelin (ET) receptor in Girardi heart (GH) cells derived from human atrium. The ET isopeptides ET-1, ET-2 and ET-3 induced the monotonous and long-lasting rise in cytosolic free Ca2+ concentration [( Ca2+]i) with almost the same potency in GH cells. Scatchard analysis of [125I]ET-1 and [125I]ET-3 binding revealed that GH cells have almost the same number of binding sites for either labeled ligand. All ET isopeptides displaced either [125I]ET-1 or [125I]ET 3 binding in GH cells almost equipotently. These results reveal that the functional ET receptors in GH cells are of the ETB-type. GH cells are the first cell line to be found to express the functional ETB-receptor. PMID- 1309937 TI - Carcinogens leave fingerprints. PMID- 1309938 TI - Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. AB - To test models of T-cell recognition, mice transgenic for T-cell receptor alpha or beta chain have been immunized with variant peptides that force changes in the resulting T-cell response. In particular, charge substitutions on the peptide often elicit reciprocal charges in the junctional (CDR3) sequences of T-cell receptor V alpha or V beta chains, indicating direct T-cell receptor-peptide contact, and allowing derivation of a topology for the T-cell receptor-MHC interaction. At one position on the peptide, variants transformed a homogeneous V beta response into a very heterogeneous one. PMID- 1309939 TI - MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. AB - Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. This error-avoiding process is catalysed by a protein encoded by the mutT gene of Escherichia coli, mutations of which increase the occurrence of A.T----C.G transversions 100 to 10,000 times the level of the wild type. Spontaneous oxidation of dGTP forms 8-oxo-7,8-dihydro-2'-dGTP (8-oxodGTP), which is inserted opposite dA and dC residues of template DNA with almost equal efficiency, and the MutT protein specifically degrades 8-oxodGTP to the monophosphate. This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis. PMID- 1309940 TI - Depletion of intracellular calcium stores activates a calcium current in mast cells. AB - In many cell types, receptor-mediated Ca2+ release from internal stores is followed by Ca2+ influx across the plasma membrane. The sustained entry of Ca2+ is thought to result partly from the depletion of intracellular Ca2+ pools. Most investigations have characterized Ca2+ influx indirectly by measuring Ca(2+) activated currents or using Fura-2 quenching by Mn2+, which in some cells enters the cells by the same influx pathway. But only a few studies have investigated this Ca2+ entry pathway more directly. We have combined patch-clamp and Fura-2 measurements to monitor membrane currents in mast cells under conditions where intracellular Ca2+ stores were emptied by either inositol 1,4,5-trisphosphate, ionomycin, or excess of the Ca2+ chelator EGTA. The depletion of Ca2+ pools by these independent mechanisms commonly induced activation of a sustained calcium inward current that was highly selective for Ca2+ ions over Ba2+, Sr2+ and Mn2+. This Ca2+ current, which we term ICRAC (calcium release-activated calcium), is not voltage-activated and shows a characteristic inward rectification. It may be the mechanism by which electrically nonexcitable cells maintain raised intracellular Ca2+ concentrations and replenish their empty Ca2+ stores after receptor stimulation. PMID- 1309941 TI - Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-permeable channel. AB - Receptor-mediated increases in the cytosolic free calcium ion concentration in most mammalian cells result from mobilization of Ca2+ from intracellular stores as well as transmembrane Ca2+ influx. Inositol 1,4,5-trisphosphate (InsP3) releases calcium from intracellular stores by opening a Ca(2+)-permeable channel in the endoplasmic reticulum. But the mechanism and regulation of Ca2+ entry into nonexcitable cells has remained elusive because the entry pathway has not been defined. Here we characterize a novel inositol 1,3,4,5-tetrakisphosphate (InsP4) and Ca(2+)-sensitive Ca(2+)-permeable channel in endothelial cells. We find that InsP4, which induces Ca2+ influx into acinar cells, enhances the activity of the Ca(2+)-permeable channel when exposed to the intracellular surface of endothelial cell inside-out patches. Our results suggest a molecular mechanism which is likely to be important for receptor-mediated Ca2+ entry. PMID- 1309942 TI - 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. AB - Vitamin A (retinol) and its natural derivatives are required for many physiological processes. The activity of retinoids is thought to be mediated by interactions with two subfamilies of nuclear retinoic acid receptors, RAR and RXR. The RARs bind all-trans retinoic acid (t-RA) with high affinity and alter gene expression as a consequence of this direct ligand interaction. RXR alpha is activated by t-RA, yet has little binding affinity for this ligand. t-RA may be converted to a more proximate ligand that directly binds and activates RXR alpha, and we have developed a method of nuclear receptor-dependent ligand trapping to test this hypothesis. Here we report the identification of a stereoisomer of retinoic acid, 9-cis retinoic acid, which directly binds and activates RXR alpha. These results suggest a new role for isomerization in the physiology of natural retinoids. PMID- 1309943 TI - Herpesvirus saimiri encodes homologues of G protein-coupled receptors and cyclins. AB - Herpesvirus saimiri (HVS) is a T-lymphotropic gammaherpesvirus which establishes asymptomatic infections in its natural host the squirrel monkey (Saimiri sciureus), but which causes fatal lymphoproliferative diseases in other New World primates. Sequencing studies show HVS is closely related to the human B lymphotropic gammaherpesvirus Epstein-Barr virus (EBV). However, despite the general colinearity between the genomes of HVS and EBV, HVS contains genes not found in EBV or in the genomes of any of the other sequenced herpesviruses. We have identified two genes, occurring in a region of divergence between HVS and EBV, that have cellular homologues. One of these, ECRF3, is homologous to the genes encoding the human cytomegalovirus (HCMV) and cellular G protein-coupled receptor family of proteins. The other HVS gene, ECLF2, is homologous to the genes encoding cellular cyclins and to our knowledge is the first reported example of a viral cyclin. The presence of G protein-coupled receptor and cyclin homologues in HVS suggests that these genes may be important in the regulation of viral and cellular processes during productive and/or latent infection of host cells, and in particular may be of relevance in the transformation and rapid proliferation of T cells during HVS infections of hosts susceptible to HVS induced lymphoproliferative diseases. PMID- 1309944 TI - Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding. AB - Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3 month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5 10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10 15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309945 TI - Molecular cloning of a calmodulin-dependent phosphatase from murine testis: identification of a developmentally expressed nonneural isoenzyme. AB - A unique isoform of the catalytic subunit of calmodulin-dependent protein phosphatase (CaM-PrP) was cloned from a murine testis library. The cDNA sequence of 1964 base pairs contained an open reading frame encoding a protein of 513 amino acids (Mr approximately 58,706), the predicted isoelectric point of which (pI 7.1) was much more basic than those of brain isoforms (pI 5.6-5.8). The deduced amino acid sequence was 77-81% identical to two other murine CaM-PrP genes and displayed a distinct Southern blot hybridization pattern, indicating that it was derived from a separate gene (type 3). High amounts of a 2800 nucleotide mRNA transcript were observed in testis, whereas mRNA species were not detectable in brain; thus, it seems likely that this CaM-PrP represents a nonneural isoenzyme. Measurements of CaM-PrP mRNA during testicular development showed a dramatic increase in expression during weeks 4-6, correlating with the later stages of spermatogenesis. These data suggest that this phosphatase isoform may be involved in germ-cell function and are consistent with the report of a flagellum-associated form of CaM-PrP that may regulate sperm motility [Tash, J. S., Krinks, M., Patel, J., Means, R. L., Klee, C. B. & Means, A. R. (1988) J. Cell Biol. 106, 1625-1633]. PMID- 1309946 TI - Primary structure and functional expression of the human cardiac tetrodotoxin insensitive voltage-dependent sodium channel. AB - The principal voltage-sensitive sodium channel from human heart has been cloned, sequenced, and functionally expressed. The cDNA, designated hH1, encodes a 2016 amino acid protein that is homologous to other members of the sodium channel multigene family and bears greater than 90% identity to the tetrodotoxin insensitive sodium channel characteristic of rat heart and of immature and denervated rat skeletal muscle. Northern blot analysis demonstrates an approximately 9.0-kilobase transcript expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. When expressed in Xenopus oocytes, hH1 exhibits rapid activation and inactivation kinetics similar to native cardiac sodium channels. The single channel conductance of hH1 to sodium ions is about twice that of the homologous rat channel and hH1 is more resistant to block by tetrodotoxin (IC50 = 5.7 microM). hH1 is also resistant to mu-conotoxin but sensitive to block by therapeutic concentrations of lidocaine in a use-dependent manner. PMID- 1309947 TI - Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease. AB - Using a monoclonal antibody directed against the primate nerve growth factor (NGF) receptor, we examined the expression of NGF receptors within neuronal perikarya of normal adult human cerebral cortex (27-98 years old) and individuals with Alzheimer disease (AD). This expression of cortical NGF receptors was compared with that seen in other neurological diseases and normal human development as well as in young and aged nonhuman primates. NGF receptor containing cortical neurons were not observed in young adults (less than 50 years old) and were observed only infrequently in non-demented elderly individuals (50 80 years old). In contrast, numerous NGF receptor-containing cortical neurons were seen in AD patients of all ages and in one 98-year-old nondemented patient. In advanced age and AD, numerous NGF receptor-positive neurons were located within laminae II-VI of temporal association cortices whereas only a few were seen in the subicular complex, entorhinal cortex, parahippocampal gyrus, and amygdaloid complex. These perikarya appeared healthy, with bipolar, fusiform, or multipolar morphologies and extended varicose dendritic arbors. These neurons failed to express neurofibrillary tangle-bearing material. In contrast to AD, NGF receptor-containing cortical neurons were not observed in Parkinson disease, Pick disease, or Shy-Drager syndrome. The NGF receptor-containing cortical neurons seen in advanced age and AD were similar in morphology to those observed in human fetal cortex. No NGF receptor-containing cortical neurons were observed in young or aged nonhuman primates. These findings suggest that neurons within the human cerebral cortex exhibit plasticity in their expression of NGF receptors in AD and extreme advanced aging. PMID- 1309948 TI - Cloning of the alpha 1 subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells. AB - The isoforms of the alpha 1 subunits of voltage-dependent Ca2+ channels expressed in human pancreatic islets were identified by using a pair of degenerate oligonucleotide primers and the polymerase chain reaction (PCR) to amplify mRNAs encoding alpha 1 subunit-like sequences. The sequences of the PCR products indicate that islets express the heart-type alpha 1 subunit as well as a second isoform whose complete sequence has not been previously reported. The sequences of cloned cDNAs encoding the human beta-cell, or neuroendocrine-type, alpha 1 subunit indicate that it is composed of 2181 amino acids. It shares 68%, 64%, and 41% identity with the sequences of the alpha 1 subunits of rabbit heart, skeletal muscle, and brain, respectively, and is predicted to have a similar structure including four homologous domains composed of six membrane-spanning segments each. RNA blotting studies indicate that the beta-cell-type alpha 1 subunit is also expressed in brain as well as in the insulin-producing cell lines RINm5F and beta TC-3; however, it could not be detected by RNA blotting in a third cell line, HIT-T15. In situ hybridization studies revealed expression of beta-cell type alpha 1 subunit mRNA in beta cells of rat pancreatic islets, implying that this protein may play a role in the regulation of insulin secretion. PMID- 1309949 TI - Regulation of DNA replication in vitro by the transcriptional activation domain of GAL4-VP16. AB - Studies of DNA viruses have provided evidence that eukaryotic transcriptional activator proteins can enhance the efficiency of DNA replication as well as transcription. The mechanism of this effect was studied in vitro using the chimeric transcription factor GAL4-VP16 and a DNA template containing GAL4 binding sites adjacent to the simian virus 40 origin of DNA replication. The binding of GAL4-VP16 prevented the repression of DNA replication which otherwise occurred when the template was assembled into chromatin. Relief of repression by GAL4-VP16 required both its DNA-binding and transcriptional activation domains but did not require RNA synthesis. The results are consistent with a general model in which transcriptional activators stimulate eukaryotic DNA replication by modifying the outcome of the competition between initiation factors and histones for occupancy of the origin. PMID- 1309951 TI - Interaction of a synthetic mitochondrial presequence with isolated yeast mitochondria: mechanism of binding and kinetics of import. AB - The mechanism of interaction of a presequence with isolated yeast mitochondria was examined. A synthetic peptide corresponding to a matrix-targeting signal was covalently labeled with a fluorescent probe. Binding of the presequence to the surface of the mitochondria and translocation of the presequence into the interior of the mitochondria could then be monitored directly in solution by measuring changes in the steady-state fluorescence of the attached fluorophore. The binding step was rapid and reversible. Quantitation of the binding under equilibrium conditions suggested that the initial association of the presequence with the surface of the mitochondria occurred by partitioning of the presequence directly into the lipid bilayer of the outer membrane. Subsequent translocation of the bound presequence into the mitochondria was monitored by measuring the rate of disappearance of presequences sensitive to digestion by added trypsin. The efficiency of translocation was high, and the rate of the translocation was dependent on the electrical potential across the inner membrane. At physiological concentrations of presequence, the rate displayed first-order kinetics with respect to the concentration of bound presequence and had a rate constant of 0.19 min-1 at 20 degrees C. Several kinetic models for the translocation of the presequence are presented that are consistent with the experimental results. PMID- 1309950 TI - Identification of a 1,25-dihydroxyvitamin D3-response element in the 5'-flanking region of the rat calbindin D-9k gene. AB - The rat calbindin D-9k gene is transcriptionally regulated by 1,25 dihydroxyvitamin D3 in the intestine. We have examined the 5'-flanking region of this gene and identified a 1,25-dihydroxyvitamin D3-responsive element (DRE) between nucleotides -489 and -445. This element confers 1,25-dihydroxyvitamin D3 responsiveness through its native promoter and the heterologous thymidine kinase promoter, and it contains the sequence GGGTGTCGGAAGCCC, which is homologous to the other previously identified DREs. Incubation of this element with the 1,25 dihydroxyvitamin D3 receptor produced a specific protein-DNA complex, which shifted to a higher molecular weight form upon the addition of a monoclonal antibody specific to the 1,25-dihydroxyvitamin D3 receptor. Therefore, the 5' flanking region of the rat calbindin D-9k gene contains a DRE that mediates the enhanced expression of this gene by 1,25-dihydroxyvitamin D3 in the intestine. PMID- 1309952 TI - Mutations in the Jun delta region suggest an inverse correlation between transformation and transcriptional activation. AB - The viral Jun protein (v-Jun) transforms chicken embryo fibroblasts (CEF) more effectively than its cellular counterpart (c-Jun). In certain cell types v-Jun is also a stronger transcriptional activator than c-Jun. These functional differences between v-Jun and c-Jun result from a deletion in v-Jun (referred to as "delta deletion") that seems to weaken the interaction of Jun with a negative cellular regulator molecule. These observations suggested that the oncogenicity of v-Jun may be due to an enhanced ability to activate transcription of target genes. To test this hypothesis, we constructed several deletions in the delta domain of chicken c-Jun and determined their transforming and transactivating properties. Surprisingly, we found an inverse correlation between the ability of the mutants to transform CEF and to transactivate the collagenase and transin promoters in CEF. In contrast, there was no significant effect of the delta mutations in c-Jun on transactivation in F9 murine embryonal carcinoma cells. The function of the delta region is therefore cell-type specific. The inverse correlation between transformation and transactivation in CEF suggests that the strong growth-promoting effect of v-Jun may be related to a failure to activate the transcription of growth attenuating genes. PMID- 1309953 TI - Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells. AB - The high-capacity glucose transporter known as GLUT-2 and the glucose phosphorylating enzyme glucokinase are thought to be key components of the "glucose-sensing apparatus" that regulates insulin release from the beta cells of the islets of Langerhans in response to changes in external glucose concentration. AtT-20ins cells are derived from anterior pituitary cells and are like beta cells in that they express glucokinase and have been engineered to secrete correctly processed insulin in response to analogs of cAMP, but, unlike beta cells, they fail to respond to glucose and lack GLUT-2 expression. Herein we demonstrate that stable transfection of AtT-20ins cells with the GLUT-2 cDNA confers glucose-stimulated insulin secretion and glucose regulation of insulin biosynthesis and also results in glucose potentiation of the secretory response to non-glucose secretagogues. This work represents a first step toward creation of a genetically engineered "artificial beta cell." PMID- 1309954 TI - An RNA pseudoknot and an optimal heptameric shift site are required for highly efficient ribosomal frameshifting on a retroviral messenger RNA. AB - Synthesis of the pol gene products of most retroviruses requires ribosomes to shift frame once or twice in the -1 direction while translating gag-pol mRNA. The viral signals for frameshifting include a heptanucleotide sequence on which the shift occurs and higher-order RNA structure just downstream of the shift site. We have made site-directed mutations in two stems (S1 and S2) of a putative RNA pseudoknot that begins 7 nucleotides 3' of the previously identified shift site (A AAA AAC) in the gag-pro region of mouse mammary tumor virus (MMTV) RNA. The mutants confirm the predicted structure, show that loss of either S1 or S2 impairs frameshifting, and exclude alternative RNA structures as significant for frameshifting. The importance of the MMTV pseudoknot has been further demonstrated by showing that shift sites from two other retroviruses function more efficiently in the position of the MMTV site than in their native contexts. However, the MMTV pseudoknot cannot promote detectable frameshifting in the absence of a recognizable upstream shift site. In addition, the species of tRNA that reads the second codon in the shift site appears to be a critical determinant, since changing the 7th nucleotide in the MMTV gag-pro shift site from C to A, U, or G severely impairs frameshifting. PMID- 1309955 TI - Could CuB be the site of redox linkage in cytochrome c oxidase? AB - This paper explores the proton pumping function of cytochrome c oxidase [ferrocytochrome-c:oxygen oxidoreductase (EC 1.9.3.1)] based upon redox linkage at the "high-potential" CuB center. A model is proposed that is derived from a redox-linked ligand exchange mechanism previously described for the CuA site. Qualitative analysis of this mechanism indicates that such a mechanism is feasible. However, the relatively short distance between CuB and cytochrome a3 implies that the uncoupling electron transfers are quite facile. In addition, the position of the CuB center with respect to the inner mitochondrial membrane argues against redox linkage at the CuB site. PMID- 1309956 TI - Alpha-helical coiled-coil stalks in the low-affinity receptor for IgE (Fc epsilon RII/CD23) and related C-type lectins. AB - The low-affinity receptor for IgE (Fc epsilon RII/CD23) is a cell surface glycoprotein that plays a role in both cellular immunity and allergic inflammation. Its extracellular IgE-binding domain bears homology to C-type animal lectins, and the protein is, therefore, classified as a member of this superfamily. We predict that this lectin-like domain is separated from the cell membrane by an extensive region of alpha-helical coiled-coil structure, based upon sequence comparisons with tropomyosin, the archetypal alpha-helical coiled coil structure, and detection of characteristic heptad repeats. Analysis of other receptor protein sequences identified a similar structural motif in other membrane-bound members of the C-type lectin superfamily, including the asialoglycoprotein receptor, the Kupffer cell receptor, and the B-cell differentiation antigen Lyb-2 (CD72). It appears that within the C-type lectin superfamily, there is a subfamily of structurally related membrane-bound receptor proteins that contain alpha-helical coiled-coil stalks of various lengths. PMID- 1309957 TI - Immunosuppression in the definitive and intermediate hosts of the human parasite Schistosoma mansoni by release of immunoactive neuropeptides. AB - Evidence supporting the concept that the parasitic trematode Schistosoma mansoni may escape immune reactions from its vertebrate (man) or invertebrate (the freshwater snail Biomphalaria glabrata) hosts by using signal molecules it has in common with these hosts was obtained by the following experiments. The presence of immunoactive proopiomelanocortin (POMC)-derived peptides [corticotropin (ACTH), beta-endorphin] in, and their release from, S. mansoni was demonstrated. Coincubation of adult worms with human polymorphonuclear leukocytes or B. glabrata immunocytes led to the appearance of alpha-melanotropin (MSH) in the medium. The conclusion that this alpha-MSH resulted from conversion of the parasite ACTH by neutral endopeptidase 24.11 (NEP) present on these cells was supported by the fact that the alpha-MSH level in the medium was markedly reduced by addition of the specific NEP inhibitor phosphoramidon. This interpretation is substantiated by the fact that no conversion was observed in comparable tests with human monocytes, which exhibit no NEP activity. alpha-MSH has the capacity to inactivate formerly active immunocytes not only from the definitive host (man, hamster) but also from the intermediate host (B. glabrata), as determined by microscopic computer-assisted examination of conformational changes. POMC-derived peptides have been detected in B. glabrata hemolymph 2, 10, and 24 days after infection by S. mansoni miracidia. Immunocytes from infected snails were found to be inactivated, and this inactivation was prevented by antibodies directed against ACTH and alpha-MSH. The immunoactive beta-endorphin released from S. mansoni does not appear to be subject to enzymatic conversion. Since it is active at lower concentrations, it may be used for distant signaling. PMID- 1309959 TI - HIV and health care providers: to test or not to test. PMID- 1309958 TI - Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection. AB - The activation of human granulocytes and invertebrate immunocytes was found to be suppressed by corticotropin (ACTH) and melanotropin (MSH). In spontaneously active granulocytes both neuropeptides caused significant conformational changes indicative of inactivity plus a reduction in their locomotion. Significant inactivation of human granulocytes by ACTH required 2 hr, that by MSH only 20 min. The addition to the incubation medium of phosphoramidon, a specific inhibitor of neutral endopeptidase 24.11, blocked inactivation of granulocytes by ACTH. Radioimmunoassay for MSH of supernatant fluids from granulocytes incubated with ACTH demonstrated a time-dependent increase in MSH. These data strongly indicate that the effect of ACTH is largely due to its conversion to MSH by granulocyte-associated neutral endopeptidase. Parallel experiments with immunocytes from the mollusc Mytilus edulis gave similar results, indicating the universality of this phenomenon. Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections. PMID- 1309960 TI - Granulocyte adhesion, deformability, and superoxide formation in acute stroke. AB - BACKGROUND AND PURPOSE: Impaired rheological properties of as well as cytotoxic substances produced by granulocytes may contribute to tissue damage in acute ischemic stroke. To assess changes in the properties of circulating granulocytes, we measured their adhesion, deformability, and superoxide generation in the first 3 days after ischemic stroke. METHODS: Granulocytes from 18 male patients and 20 age- and risk-matched controls were investigated. Adhesion to murine laminin-, human fibronectin-, and bovine serum albumin-coated surfaces was measured with and without the stimulus phorbol myristate acetate and the antiadhesion antibody IB4. Superoxide anion formation was assessed by the reduction of ferricytochrome C. In a subgroup of 10 patients and 11 controls, granulocyte deformability was determined using the micropipette aspiration technique. RESULTS: The patients had significantly greater granulocyte adhesion to laminin (p less than 0.005) and fibronectin (p less than 0.05) but not bovine serum albumin. Cell stimulation enhanced the differences between the groups, whereas the antiadhesion antibody inhibited adhesion in both patients and controls. There were no significant differences in granulocyte deformability. Superoxide production by granulocytes was significantly lower in the patients without the stimulus (p less than 0.05) and with 10 nM phorbol myristate acetate (p less than 0.005). CONCLUSIONS: These findings suggest that circulating granulocytes in ischemic stroke exhibit increased adhesive properties, a feature that represents one of the risk factors for granulocyte entrapment, impairment of microvascular flow, and tissue injury. PMID- 1309962 TI - Cardiac surgery causes desensitization of the beta-adrenergic receptor system of human lymphocytes. AB - Thirteen patients undergoing cardiac surgery were studied to examine whether beta adrenergic desensitization occurs in the perioperative period surrounding cardiac surgery, using peripheral blood lymphocytes as a model. Lymphocytes were isolated before induction of anesthesia (PRE) and on the morning of the first postoperative day (POST). Cyclic adenosine monophosphate (cAMP) production from the lymphocytes was assayed in the untreated (BASAL) state, and after treatment with 5 microM isoproterenol, 10 microM prostaglandin E1, or 20 mM sodium fluoride with 10 microM AlCl3 (NaF). All cAMP values are reported as picomoles per 10(6) cells, mean +/- SEM. BASAL cAMP production did not change significantly between the PRE and POST samples (PRE, 1.2 +/- 0.1; POST, 1.0 +/- 0.1). Isoproterenol stimulated cAMP was significantly lower postoperatively (PRE, 8.36 +/- 0.9; POST, 5.1 +/- 0.5; P less than 0.005). Prostaglandin E1-stimulated cAMP did not change (PRE, 21.7 +/- 2.4; POST, 25.3 +/- 2.5), and NaF-stimulated cAMP was increased postoperatively (PRE, 8.8 +/- 1.6; POST, 14.3 +/- 2.0; P less than 0.05). These findings suggest that cardiac surgery and/or cardiopulmonary bypass results in significant desensitization of the beta-adrenergic receptor/adenylate cyclase system of lymphocytes, which may parallel changes in the adrenergic response of other organ systems. PMID- 1309961 TI - Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. An immunoelectron microscopy study. AB - The authors used an immunogold labeling procedure to investigate the redistribution of platelet receptors and their ligands on the surface of contact activated adherent platelets before and after thrombin stimulation. During the initial stage of platelet adhesion, a typical segregation of receptors occurred. Gold particles identifying glycoprotein (GP) Ib (CD42b) and GPIIb-IIIa (CD41a) remained distributed over the entire platelet surface, whereas gold particles identifying GPIa-IIa (CDw 49b) and GPIV (CD36) were found essentially overlying the granulomere; p24 (CD9) was present at the peripheral platelet rim and over the cell body. An increased labeling of GPIIb-IIIa, GPIV and p24 was also observed on pseudopods, with GPIIb-IIIa and GPIV concentrated at the enlarged extremities and at sites of contact between two platelets, whereas GPIb was absent from pseudopods. After thrombin stimulation of adherent platelets, GPIb underwent a relocation to the cell center, in contrast to GPIIb-IIIa which still remained randomly distributed over the cell body. To investigate whether ligand distribution paralleled this receptor segregation, platelet released von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP) were visualized. During the early stages of platelet activation, surface labeling for all three adhesive proteins was minimal and almost undetectable. Occasionally, intragranular Fg and vWF was accessible to gold-coupled antibodies, with vWF exhibiting the typical eccentric alpha-granular localization. At later stages of activation and especially after thrombin stimulation, no surface labeling for vWF was observed, whereas immunogold particles identifying vWF were still present inside enlarged clear vacuoles. In contrast, labeling of Fg and TSP was increased over the granulomere and extended to the cell periphery and the pseudopods, but was absent from the hyalomere, despite the presence of GPIIb-IIIa molecules. Double labeling experiments showed colocalization of Fg and TSP, GPIV and TSP, as well as Fg and GPIIb-IIIa, although no typical coclustering of GPIIb-IIIa and GPIV or GPIIb-IIIa and p24 was apparent. Our results further suggest that 1) on surface activated adherent platelets, not all GPIIb-IIIa molecules become competent to bind Fg, 2) GPIa-IIa is not anchored to the platelet membrane skeleton, and 3) during the early stage of platelet activation, a communication exists between the alpha granules and the platelet surface. PMID- 1309963 TI - Airway mucosal inflammation in occupational asthma induced by toluene diisocyanate. AB - We examined the light and electron microscopic structure of lobar bronchial biopsies of nine subjects with occupational asthma induced by toluene diisocyanate (TDI) and of four control nonasthmatic subjects who had never been exposed to TDI. Inflammatory cell numbers were separately assessed in the intact epithelium, in the more superficial layer of the submucosa, and in the total submucosa. Asthmatic subjects had an increased number of inflammatory cells in the airway mucosa compared with control subjects. Eosinophils were significantly increased in all compartments, CD45-positive cells were significantly increased in the epithelium and in the more superficial layer of the submucosa, and mast cells were significantly increased only in epithelium. By electron microscopy eosinophils and mast cells appeared degranulated only in asthmatic patients. In the areas of epithelium that appeared intact by light microscopy, electron microscopy showed that, although the intercellular spaces between columnar cells were similar in asthmatic and control groups, the intercellular spaces between basal cells were significantly wider in patients with asthma. Patients with TDI induced asthma also had a thicker subepithelial reticular layer, where immunohistochemistry showed the presence of collagen III. In conclusion, in patients with asthma induced by TDI, the airway mucosa shows pathologic features, such as inflammatory cell infiltrate and thickening of subepithelial collagen, similar to those described in atopic asthma. PMID- 1309964 TI - Effect of cessation of exposure to toluene diisocyanate (TDI) on bronchial mucosa of subjects with TDI-induced asthma. AB - The effect of cessation of exposure to toluene diisocyanate (TDI) was studied in six patients with TDI-induced asthma, proved by a positive inhalation challenge with TDI. Bronchial challenges with TDI and methacholine were performed, and lobar bronchial biopsies were taken at diagnosis and 6 months later, after cessation of exposure. Biopsies from four nonasthmatic control subjects were also examined. At diagnosis, asthmatic subjects had thickened reticular basement membrane (p less than 0.05) and increased numbers of mononuclear cells (p less than 0.05) and eosinophils (p less than 0.05) in the lamina propria when compared with control subjects. Electron microscopy showed degranulation of eosinophils and mast cells in asthmatics. Six months after cessation of exposure, the thickness of reticular basement membrane was significantly reduced compared with that at diagnosis (p less than 0.05), and it decreased to values similar to those of control biopsies. Inflammatory cell numbers in bronchial mucosa of asthmatic subjects did not change significantly 6 months after removal from exposure, and degranulation of eosinophils and mast cells was still present. At the end of the study, airway hyperresponsiveness to methacholine and/or sensitivity to TDI persisted in most of the asthmatic patients despite the cessation of exposure and the disappearance of asthmatic symptoms. In conclusion, in patients with occupational asthma induced by TDI, the avoidance of exposure to the sensitizing agent for 6 months is able to reverse the reticular basement membrane thickening in the bronchial mucosa, but the inflammatory cell infiltrate, the specific sensitivity to TDI, and the nonspecific airway hyperreactivity may persist. PMID- 1309965 TI - Effect of iron chelators on paraquat toxicity in rats and alveolar type II cells. AB - There is general agreement that the lung damage seen in paraquat poisoning is due to the generation of free radicals in alveolar epithelial cells. We have recently shown that the iron chelator and antioxidant deferoxamine (DF) reduces the mortality caused by paraquat in vitamin-E-deficient rats. In the present study we investigated the effect of DF and the lipid soluble iron chelator compound 51 (CP51) of the hydroxypyridin-4-one family on paraquat poisoning in rats with a normal vitamin E status and on isolated alveolar type II cells (ATTC). Adult rats were intravenously injected with a lethal dose of paraquat (40 mg/kg) while concurrent treatment with a continuous intravenous infusion of DF or CP51 was started. Survival of rats receiving DF at 25 and 50 mg/kg/24 h was not significantly increased compared with PBS-treated control animals. CP51, however, significantly (p less than 0.01) reduced the mortality caused by paraquat. When rats were treated with 25 mg/kg/24 h, eight of 15 rats survived the study period of 35 days compared with three in the PBS-treated control group (n = 27). In ancillary in vitro studies radiolabeled [51Cr]ATTC were incubated in a medium containing 100 microM paraquat in the absence or presence of DF and CP51. Paraquat-induced ATTC lysis increased to approximately 25% after 7 h of incubation. At the highest tested concentration (500 microM) of chelator, injury decreased markedly (80%), whereas at the lowest tested concentration (50 microM) cytotoxicity was not prevented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1309966 TI - A familial lymphoproliferative disorder presenting with primary pulmonary manifestations. AB - A familial lymphoproliferative disorder presented in three male siblings with primary pulmonary involvement manifested as either lymphoid interstitial pneumonia or an angiodestructive polymorphous infiltrate morphologically resembling lymphomatoid granulomatosis. The polymorphous infiltrate consisted chiefly of mature T-cells with a few B-cells and plasma cells, and gene rearrangement studies failed to show clonality. Epstein-Barr virus, frequently associated with proliferative lesions in males in the X-linked lymphoproliferative syndrome, was not demonstrated in any of the pulmonary lesions. An HLA haplotype shared among the affected siblings was A1, B8, DR4. The unusual clinical presentation plus the lack of involvement by EBV in the pulmonary lesions suggests that this is a previously undescribed familial lymphoproliferative disorder. PMID- 1309967 TI - Activity in vitro of rifabutin, FCE 22807, rifapentine, and rifampin against Mycobacterium microti and M. tuberculosis and their penetration into mouse peritoneal macrophages. AB - The activities of the rifamycins, rifabutin, FCE 22807, rifapentine, and rifampin, were studied within unstimulated peritoneal macrophages infected with Mycobacterium microti and in cultures of M. microti and M. tuberculosis in 7H-9 medium without Tween 80. In macrophage cultures, serial rifamycin concentrations were added after a 2.5 h phagocytosis period, and viable counts were done after incubation for 5 to 6 days. To ensure comparability with the daily drug replacements in the macrophage experiments, the period of exposure to serial rifamycin concentrations in 7H-9 medium was kept to only 3 days. The MICs of M. microti and M. tuberculosis were similar. The MICs of rifabutin and FCE 22807 were 2.5 times lower and that of rifapentine 1.7 times lower than the MIC of rifampin. None of the rifamycins were concentrated in macrophages, the MICs being higher in the macrophages than in vitro by a factor of 2-fold for rifabutin, 6.7 fold for rifampin, 20-fold for FCE 22807, and 26-fold for rifapentine. PMID- 1309968 TI - Release of peptide leukotriene into nasal secretions after local instillation of aspirin in aspirin-sensitive asthmatic patients. AB - Although the mechanism of aspirin-induced asthma and rhinitis is unknown, it has been suggested that adverse nasal and bronchial reactions are caused by an increased production of lipoxygenase products. In examining this hypothesis we have measured the release of peptide leukotrienes (PeptLTs), 15-HETE, and prostaglandins in nasal fluids obtained by nasal lavages after instillation of acetylsalycilic acid (ASA) and placebo (saline). Ten ASA-sensitive asthmatics, 10 ASA-insensitive asthmatics, and seven healthy subjects were challenged in a double-blind study with normal saline and 12 mg of ASA. Twelve mg were administered based on the results of a previous study that showed that this dose caused minor to moderate symptoms in ASA-sensitive patients. PeptLTs, LTB4, 15 HETE, PGE2, PGF2 alpha, and PGD2 were measured by radioimmunoassay methods. Significant levels of PeptLTs were detected in sensitive asthmatic patients 60 min after nasal challenge. This change was associated with a significant increase in symptoms. No increase in PeptLTs levels were found, however, in either insensitive patients or healthy subjects. Inhibition of PGE2 and PGF2 alpha release was detected in the three groups after ASA administration. ASA also inhibited PGD2 release in insensitive asthmatic patients but not in both sensitive patients and healthy subjects. These results suggest that an abnormal release of PeptLTs in ASA-sensitive asthmatic patients contributes to nasal and bronchial adverse reactions. The lack of effects on PGD2 release suggests that mast cells from ASA-insensitive patients are more sensitive to ASA than those from sensitive asthmatic patients and healthy subjects. PMID- 1309969 TI - Neutrophil chemotactic factors in the respiratory tract of patients with chronic airway diseases or idiopathic pulmonary fibrosis. AB - This study was designed to clarify the contributions of specific neutrophil chemotactic factors (NCF) in neutrophil accumulation in the human respiratory tract associated with various diseases. The activity and characteristics of the NCF in the bronchoalveolar lavage (BAL) fluid and culture media of alveolar macrophages obtained from normal volunteers, control patients, patients with chronic airway diseases (CAD) and patients with idiopathic pulmonary fibrosis (IPF) were examined. The BAL fluid from normal volunteers contained NCF comparable with the chemotactic factors interleukin-8 (IL-8) and leukotriene B4 (LTB4). Analysis of the biochemical characteristics of NCF released from alveolar macrophages suggests that they are derived from alveolar macrophages. The NCF activities in BAL fluids from patients with CAD and IPF were higher than those in BAL fluids from normal volunteers and control patients. Biochemical analysis demonstrated that several kinds of NCF, including those derived from the complement component C5 and alveolar macrophages, were present in the BAL fluid from patients with CAD and respiratory infections. The especially marked increase of C5-derived NCF indicate their importance in neutrophil accumulation in the respiratory tract of patients with CAD. Alveolar macrophages released different types of NCF after different lengths of culture periods (4 h and 24 h). Alveolar macrophages from patients with IPF released larger amounts of NCF than alveolar macrophages from normal volunteers, indicating the importance of alveolar macrophage-derived NCF as well as C5-derived NCF in neutrophil accumulation in the respiratory tract of patients with IPF. These results suggest that various types of NCF increase in response to different disease states of the respiratory tract and serve to regulate the accumulation of neutrophils. PMID- 1309970 TI - Cytokines: from clone to clinic. PMID- 1309971 TI - Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases. AB - Two protein inhibitors of metalloproteinases (TIMP) were isolated from medium conditioned by the clonal rat osteosarcoma line UMR 106-01. Initial purification of both a 30-kDa inhibitor and a 20-kDa inhibitor was accomplished using heparin Sepharose chromatography with dextran sulfate elution followed by DEAE-Sepharose and CM-Sepharose chromatography. Purification of the 20-kDa inhibitor to homogeneity was completed with reverse-phase high-performance liquid chromatography. The 20-kDa inhibitor was identified as rat TIMP-2. The 30-kDa inhibitor, although not purified to homogeneity, was identified as rat TIMP-1. Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues. Treatment with peptide:N-glycosidase F indicated that the 30-kDa rat inhibitor is glycosylated while the 20-kDa inhibitor is apparently unglycosylated. Inhibition of both rat and human interstitial collagenase by rat TIMP-2 was stoichiometric, with a 1:1 molar ratio required for complete inhibition. Exposure of UMR 106-01 cells to 10(-7) M parathyroid hormone resulted in approximately a 40% increase in total inhibitor production over basal levels. PMID- 1309972 TI - Cytochrome c2 mutants of Rhodobacter capsulatus. AB - Although structurally related to other members of the class I c-type cytochromes, the cytochromes c2 have little amino acid sequence homology to the eukaryotic cytochromes c. Moreover, the cytochromes c2 exhibit distinct properties such as redox potential and an isoelectric point. In an effort to understand the differences between the cytochromes c2 and the other class I c-type cytochromes, we have developed a genetic system to study Rhodobacter capsulatus cytochrome c2 by site-directed mutagenesis. We describe here overproduction of R. capsulatus wild-type cytochrome c2 in cytochrome c2-minus strains of R. capsulatus and Rhodobacter sphaeroides. We demonstrate that R. capsulatus wild-type cytochrome c2 can transcomplement for photosynthetic growth in R. sphaeroides. Further, we describe the generation, expression, and in vivo functionality properties of nine R. capsulatus site-directed mutants. We show that mutants K12D, K14E, K32E, K14E/K32E, P35A, W67Y, and Y75F are overproduced and functional in vivo. In contrast, mutants Y75C and Y75S are expressed at low levels and exhibit poor functionality in vivo. These findings establish an effective system for the production of R. capsulatus site-directed mutants and demonstrate that interspecies complementation can be used to detect defective cytochrome c2 mutants. PMID- 1309973 TI - Stereochemistry of D-galactal and D-galacto-octenitol hydration by coffee bean alpha-galactosidase: insight into catalytic functioning of the enzyme. AB - Green coffee bean alpha-galactosidase was found to catalyze the hydration of D galactal and (Z)-3,7-anhydro-1,2-dideoxy-D-galacto-oct-2-enitol (D-galacto octenitol), each a known substrate for beta-galactosidase. The hydration of D galactal by the alpha-galactosidase in D2O yielded 2-deoxy-2(S)-D-[2 2H]galactose; the hydration of D-[2-2H]galacto-octenitol in H2O yielded 1,2 dideoxy-2(R)-D-[2-2H]galactooct-3-ulose. Thus, the enzyme protonated each substrate from beneath the plane of the ring, as assumed for alpha-D galactosides. These results provide an unequivocal assignment of the orientation of an acidic catalytic group to the alpha-galactosidase reaction center. In addition, they reveal a pattern of glycal/exocyclic enitol/glycoside protonation by the enzyme that differs from the pattern reported for beta-galactosidase and from that reported for alpha-glucosidases. Further findings show that D-galacto octenitol is hydrated by the coffee bean alpha-galactosidase to form the alpha anomer of 1,2-dideoxy-D-galactooctulose and by Escherichia coli beta galactosidase to form the beta-anomer. That each enzyme converts this enolic substrate to a product whose de novo anomeric configuration matches that formed from its D-galactosidic substrates provides new evidence for the role of protein structure in controlling the steric outcome of reactions catalyzed by these and other glycosylases. The findings are discussed in light of the concept that catalysis by glycosidases involves a "plastic" protonation phase and a "conserved" product configuration phase. PMID- 1309974 TI - Direct interaction between the internal NADH: ubiquinone oxidoreductase and ubiquinol:cytochrome c oxidoreductase in the reduction of exogenous quinones by yeast mitochondria. AB - The reduction of duroquinone (DQ) and 2,3-dimethoxy-5-methyl-6-decyl-1,4 benzoquinone (DB) by NADH and ethanol was investigated in intact yeast mitochondria with good respiratory control ratios. In these mitochondria, exogenous NADH is oxidized by the NADH dehydrogenase localized on the outer surface of the inner membrane, whereas the NADH produced by ethanol oxidation in the mitochondrial matrix is oxidized by the NADH dehydrogenase localized on the inner surface of the inner membrane. The reduction of DQ by ethanol was inhibited 86% by myxothiazol; however, the reduction of DQ by NADH was inhibited 18% by myxothiazol, suggesting that protein-protein interactions between the internal (but not the external) NADH: ubiquinone oxidoreductase and ubiquinol:cytochrome c oxidoreductase (the cytochrome bc1 complex) are involved in the reduction of DQ by NADH. The reduction of DQ and DB by NADH and ethanol was also investigated in mutants of yeast lacking cytochrome b, the iron-sulfur protein, and ubiquinone. The reduction of both quinone analogues by exogenous NADH was reduced to levels that were 10 to 20% of those observed in wild-type mitochondria; however, the rate of their reduction by ethanol in the mutants was equal to or greater than that observed in the wild-type mitochondria. Furthermore, the reduction of DQ in the cytochrome b and iron-sulfur protein lacking mitochondria was myxothiazol sensitive, suggesting that neither of these proteins is an essential binding site for myxothiazol. The mitochondria from the three mutants also contained significant amounts of antimycin- and myxothiazol-insensitive NADH:cytochrome c reductase activity, but had no detectable succinate:cytochrome c reductase activity. These results suggest that the mutants lacking a functional cytochrome bc1 complex have adapted to oxidize NADH. PMID- 1309975 TI - Rose bengal activates the Ca2+ release channel from skeletal muscle sarcoplasmic reticulum. AB - The photooxidizing xanthene dye rose bengal (10 nM to 1 microM) stimulates rapid Ca2+ release from skeletal muscle sarcoplasmic reticulum vesicles. Following fusion of sarcoplasmic reticulum (SR) vesicles to an artificial bilayer, reconstituted Ca2+ channel activity is stimulated by nanomolar concentrations of rose bengal in the presence of a broad-spectrum light source. Rose bengal does not appear to affect K+ channels present in the SR. Following reconstitution of the sulfhydryl-activated 106-kDa Ca2+ channel protein into a bilayer, rose bengal activates the isolated protein in a light-dependent manner. Ryanodine at a concentration of 10 nM is shown to lock the 106-kDa channel protein in a subconductance state which can be reversed by subsequent addition of 500 nM rose bengal. This apparent displacement of bound ryanodine by nanomolar concentrations of rose bengal is also directly observed upon measurement of [3H]ryanodine binding to JSR vesicles. These observations indicate that photooxidation of rose bengal causes a stimulation of the Ca2+ release protein from skeletal muscle sarcoplasmic reticulum by interacting with the ryanodine binding site. Furthermore, similar effects of rose bengal on isolated SR vesicles, on single channel measurements following fusion of SR vesicles, and following incorporation of the isolated 106-kDa protein strongly implicates the 106-kDa sulfhydryl activated Ca2+ channel protein in the Ca2+ release process. PMID- 1309976 TI - Different effects of hypochlorous acid on human neutrophil metalloproteinases: activation of collagenase and inactivation of collagenase and gelatinase. AB - Human neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) produce the reactive oxidant hypochlorous acid (HOCl) and release the matrix metalloproteinases collagenase and gelatinase from secretory granules. We have investigated the stoichiometry of activation and inactivation of the two metalloproteinases with HOCl. HOCl activated purified neutrophil procollagenase at ratios between 10 and 40 mol of HOCl/mol enzyme, but caused inactivation at higher ratios. Maximum activation was about the same as that achieved by p aminophenyl-mercuric acetate. However, less than a third of the total collagenase released from PMA-stimulated neutrophils was activated by coreleased HOCl and most of the activity was destroyed after 1 h of stimulation. These results indicate that the HOCl/enzyme ratio must fall within a narrow range for activation to occur. In contrast to collagenase, purified progelatinase underwent negligible activation (2.5 +/- 1.2%) at HOCl/enzyme molar ratios less than 30 and was destroyed at higher ratios. Likewise no active gelatinase could be detected in supernatant from PMA-stimulated cells and almost all of the proenzyme was destroyed by HOCl after 60 min stimulation. Our results illustrate that only collagenase can be activated by HOCl in vitro and that gelatinase is much more sensitive to inactivation. Since a precise HOCl/enzyme ratio is required for collagenase activation it is doubtful whether effective enzyme regulation by HOCl could occur in vivo where various HOCl scavengers are present. PMID- 1309977 TI - Generation of superoxide during the enzymatic action of tyrosinase. AB - Evidence for the generation of superoxide anion in an enzymatic action of tyrosinase is reported. In the dopatyrosinase reaction, 1 mol of O2 is required for the production of 2 mol of dopaquinone, 1 mol of dopachrome, and 1/4 mol of O2-. Superoxide dismutase and 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-a]pyrazin 3-one (a chemiluminescence probe and O2 trap) do not inhibit the rate of dopachrome formation from dopa in the presence of tyrosinase, indicating that free O2- is not utilized for metabolizing dopa. ESR studies for the accumulation of semiquinone radicals generated from tyrosine and N-acetyltyrosine in the presence of tyrosinase imply that O2- is not generated by the semiquinone + O2 reaction. Since the addition of H2O2 and dopa to tyrosinase promotes the release of O2- and formation of dopachrome, the Cu(II)O2-Cu(I) complex could be formed as a intermediate (an active form of tyrosinase); [Cu(II)]2 + H2O2 in equilibrium Cu(I)O2-Cu(II) + 2H+. PMID- 1309979 TI - Evidence of dithionite contribution to the low-frequency resonance Raman spectrum of reduced and mixed-valence cytochrome c oxidase. AB - The resonance Raman spectra of deoxygenated solutions of mixed-valence cyanide bound and fully reduced cytochrome oxidase derivatives that have been reduced in the presence of aqueous or solid sodium dithionite exhibit two new low-frequency lines centered at 474 and 590 cm-1. These lines were not observed when the reductant system was changed to a solution containing ascorbate and N,N,N',N' tetramethyl-p-phenylenediamine (TMPD). Under enzyme turnover conditions, the addition of dithionite to the reoxidized protein (the 428-nm or "oxygenated" form) increases the intensity of these lines, while reoxidation and rereduction of the enzyme in the presence of ascorbate/TMPD resulted in the absence of both lines. Our data suggest that both lines must have contributions from species formed from aqueous dithionite, presumably the SO2 species, since these two lines are also observed in the Raman spectrum of a solution of aqueous dithionite, but not in the spectrum of an ascorbate/TMPD solution. Since heme metal-ligand stretch vibrations are expected to appear in the low-frequency region from 215 to 670 cm-1, our results indicate that special care should be exercised during the interpretation of the cytochrome a3 resonance Raman spectrum. PMID- 1309978 TI - Regulation of a cytochrome c2 isoform in wild-type and cytochrome c2 mutant strains of Rhodobacter sphaeroides. AB - In Rhodobacter sphaeroides, mutations that suppress the photosynthetic deficiency (spd mutations) of strains lacking cytochrome c2 (cyt c2) cause accumulation of a periplasmic cyt c2 isoform that has been designated isocytochrome c2 (isocyt c2). In this study, a new method for purification of both cyt c2 and isocyt c2 is described that uses periplasmic fluid as a starting material. In addition, antiserum to isocyt c2 has been used to demonstrate that all suppressor mutants contain an isocyt c2 of approximately 15 kDa. Western blot analysis indicates that isocyt c2 was present at lower levels in both wild-type and cyt c2 mutants than in spd-containing mutants. Although isocyt c2 is detectable under all growth conditions in wild-type cells, the highest level of isocyt c2 is present under aerobic conditions. Our results demonstrate that spd mutations increase the steady state level of isocyt c2 under photosynthetic conditions. Although the physiological function of isocyt c2 in wild-type cells is not known, we show that a nitrate-regulated protein in Rhodobacter sphaeroides f. sp. denitrificans also reacts with the isocyt c2 antiserum. PMID- 1309980 TI - Glucose 1,6-bisphosphate-overloaded erythrocytes: a strategy to investigate the metabolic role of the bisphosphate in red blood cells. AB - Human erythrocytes overloaded with glucose 1,6-bisphosphate were prepared in order to establish the metabolic significance of this phosphorylated sugar in the intact red cell. The intracellular glucose 1,6-bisphosphate concentration was increased six- and twofold over the normal level by encapsulating (i) the commercially available compound and (ii) the glucose 1,6-bisphosphate synthase obtained from rabbit skeletal muscle, respectively. In both experimental conditions, a reduction of glucose utilization by the loaded cells was observed after reequilibration to the steady state. At the steady state, the concentrations of the glycolytic intermediates and of the adenine nucleotides appeared substantially unmodified when compared with those of controls, with the exception of a 50% reduction of glucose and fructose 6-phosphate measured in erythrocytes encapsulated with exogenous glucose 1,6-bisphosphate. Under the considered experimental conditions, the elevated intracellular glucose 1,6 bisphosphate appears to display an inhibitory effect on hexokinase that overcomes the possible activation of phosphofructokinase or pyruvate kinase. PMID- 1309981 TI - Mechanism of reaction of a suggested superoxide-dismutase mimic, Fe(II)-N,N,N',N' tetrakis(2-pyridylmethyl)ethylenediamine. AB - The interaction of a recently developed intracellular superoxide dismutase analogue, Fe(II)-N,N,N',N'-tetrakis(2- pyridylmethyl)ethylenediamine (Fe(II) TPEN), with reactive oxygen species was investigated under in vitro conditions. The complex catalyzed the dismutation of enzyme- or radiolysis-generated superoxide with the production of H2O2; under steady-state conditions the equilibrium was strongly shifted toward Fe(III)-TPEN. Fe(II)-TPEN reacted with H2O2 to generate hydroxyl radicals in a Fenton reaction. The oxidized Fe(III) TPEN was readily reduced by ascorbate or glutathione. Given the capacity to produce hydroxyl radicals and the reaction with cellular reductants it seems unlikely that Fe-TPEN may find widespread use as an intracellular superoxide dismutase substitute. PMID- 1309982 TI - The phospholamban phosphatase associated with cardiac sarcoplasmic reticulum is a type 1 enzyme. AB - Canine cardiac sarcoplasmic reticulum vesicles contain intrinsic protein phosphatase activity, which can dephosphorylate phospholamban and regulate calcium transport. This phosphatase has been suggested to be a mixture of both type 1 and type 2 enzymes (E. G. Kranias and J. Di Salvo, 1986, J. Biol. Chem. 261, 10,029-10,032). In the present study the sarcoplasmic reticulum phosphatase activity was solubilized with n-octyl-beta-D-glucopyranoside and purified by sequential chromatography on DEAE-Sephacel, polylysine-agarose, heparin-agarose, and DEAE-Sephadex. A single peak of phosphatase activity was eluted from each column and it was coincident for both phospholamban and phosphorylase a, used as substrates. The partially purified phosphatase could dephosphorylate the sites on phospholamban phosphorylated by either cAMP-dependent or calcium-calmodulin dependent protein kinase(s). Enzymatic activity was inhibited by inhibitor-2 and by okadaic acid (I50 = 10-20 nM), using either phosphorylase a or phospholamban as substrates. The sensitivity of the phosphatase to inhibitor-2 or okadaic acid was similar for the two sites on phospholamban, phosphorylated by the cAMP dependent and the calcium-calmodulin-dependent protein kinases. Phospholamban phosphatase activity was enhanced (40%) by Mg2+ or Mn2+ (3 mM) while Ca2+ (0.1-10 microM) had no effect. These characteristics suggest that the phosphatase associated with cardiac sarcoplasmic reticulum is a type 1 enzyme, and this activity may participate in the regulation of Ca2+ transport through dephosphorylation of phospholamban in cardiac muscle. PMID- 1309983 TI - Dibutyryl cAMP enhances the effect of 1,25-dihydroxyvitamin D3 on a human promyelocytic leukemia cell, HL-60, at both the receptor and the postreceptor steps. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) induces differentiation of a human promyelocytic leukemia cell line, HL-60, into monocytes/macrophages, and 25 hydroxyvitamin D3- and 1,25-(OH)2D3-24-hydroxylase activities in HL-60 mitochondria via a steroid-hormone receptor mechanism. Dibutyryl cyclic adenosine monophosphate (dbcAMP), a granulocyte inducer, significantly augmented the differentiation-inducing effect of 1,25-(OH)2D3 along the monocyte/macrophage pathway. Furthermore, dbcAMP significantly potentiated the effect of 1,25-(OH)2D3 on HL-60 cells to hydroxylate 1,25-(OH)2[26,27-3H]D3 to form 1,24,25-(OH)3[26,27 3H]D3. DbcAMP seemed to augment the effect of 1,25-(OH)2D3 in part through upregulation of the 1,25-(OH)2D3 receptor, because 10(-7) M dbcAMP increased 1,25 (OH)2D3 receptor levels approximately 2.3-fold, which was similar to a 1.9-fold augmentation by the same concentrations of dbcAMP of 1,25-(OH)2D3-induced cell characteristics to hydroxylate C-24 of 1,25-(OH)2[26,27-3H]D3. However, dbcAMP is also known to enhance HL-60 cell differentiation caused by other differentiation inducers. We have established another HL-60 clone which acquires resistance to 1,25-(OH)2D3 in the induction of cell differentiation by a defect at the postreceptor step, as reflected by resistance to other differentiation inducers, such as retinoic acid and dimethyl sulfoxide. Even in this resistant clone, dbcAMP significantly enhanced the differentiation-inducing effect of 1,25 (OH)2D3. Of interest, this clone showed resistance to dbcAMP in the induction of cell differentiation. Furthermore, we have demonstrated that intracellular cAMP levels were significantly lower in uremic serum-treated cells than in cells treated with normal human serum and that a significant positive correlation was found between intracellular cAMP levels and 1,25-(OH)2D3-induced cell differentiation. These data indicated that the intracellular cAMP level is one of the major determinants of 1,25-(OH)2D3-induced HL-60 cell differentiation and that dbcAMP could enhance the effects of 1,25-(OH)2D3 on HL-60 cells not only by increasing 1,25-(OH)2D3 receptor levels but also at the postreceptor step. PMID- 1309984 TI - Oxidant-induced mobilization of zinc from metallothionein. AB - Neutrophils which accumulate at sites of inflammation secrete a number of injurious oxidants which are highly reactive with protein sulfhydryls. The present study examined the possibility that this reactivity with thiols may cause protein damage by mobilizing zinc from cellular metalloproteins in which the metal is bound to cysteine. The ability of the three principal neutrophil oxidants, hypochlorous acid (HOCl), superoxide (.O2-), and hydrogen peroxide (H2O2), to cleave thiolate bonds and mobilize complexed zinc was compared using two model compounds (2,3-dimercaptopropanol and metallothionein peptide fragment 56-61), as well as metallothionein. With all compounds, 50 microM HOCl caused high rates of Zn2+ mobilization as measured spectrophotometrically with the metallochromic indicator 4-(2-pyridylazo)resorcinol. Xanthine (500 microM) plus xanthine oxidase (30 mU), which produced a similar concentration of .O2-, also effected a rapid rate of Zn2+ mobilization which was inhibited by superoxide dismutase but not catalase, indicating that .O2- is also highly reactive with thiolate bonds. In contrast, H2O2 alone was much less reactive at comparable concentrations. These data suggest that HOCl and .O2- can cause damage to cellular metalloproteins through the mobilization of complexed zinc. In view of the essential role played by zinc in numerous cellular processes, Zn2+ mobilization by neutrophil oxidants may cause significant cellular injury at sites of inflammation. PMID- 1309985 TI - Undermethylation and DNase I hypersensitivity of myeloperoxidase gene in HL-60 cells before and after differentiation. AB - Methylation and DNase I-hypersensitive sites of the myeloperoxidase gene in human myeloid leukemia HL-60 cells were studied by Southern blot hybridization using the myeloperoxidase gene probes. Digestion of DNA with a methylation-sensitive restriction endonuclease indicated that a CpG in the CCGG sequence located 3.53 kbp upstream of the myeloperoxidase gene was unmethylated in HL-60 cells expressing the gene, whereas it was methylated in K562 cells and human placenta not expressing the gene. The site in HL-60 cells remained unmethylated after retinoic acid- or 12-O-tetradecanoyl-phorbol-13-acetate-induced differentiation that arrests myeloperoxidase synthesis. Digestion of isolated nuclei with various amounts of DNase I indicated that four DNase I-hypersensitive sites were in an upstream region of the myeloperoxidase gene in HL-60 cells and three sites were within the gene. In retinoic acid-induced cells, the bands of the hypersensitive site near the 5' side of the gene and that in the first intron became weak, while that of the site in the fifth intron became strong. The bands of these hypersensitive sites were weak in K562 cells. The implications of these changes in tissue-specific expression and developmental down-regulation of the myeloperoxidase gene are discussed. PMID- 1309986 TI - Characterization of ubisemiquinone radicals in succinate-ubiquinone reductase. AB - A thenoyl trifluoroacetone-sensitive and antimycin-insensitive ubisemiquinone radical (Qs) is readily detected in purified succinate-cytochrome c reductase. When this reductase is resolved into succinate-Q and ubiquinol-cytochrome c reductases, Qs was not detected in either reductase. The difficulty in detecting such a radical in purified succinate-Q reductase has puzzled investigators for years. A deficiency of Q in the isolated complex is the reason for the failure to detect Qs. Upon addition of exogenous Q, a thenoyl trifluoroacetone-sensitive Q radical is readily detectable in isolated succinate-Q reductase under a controlled redox potential. Maximum radical concentration is observed when 5 mol of exogenous Q, per mole of flavin, is added. The radical gives an EPR signal with a g-value of 2.005 and a line-width of 12 G. The Em of Qs is 84 mV at pH 7.4, with half-potentials of E1 = 40 mV and E2 = 128 mV. The Qs-radical does not show power saturation, even at 200 mW. PMID- 1309987 TI - Degradation of cytochrome P450 2E1: selective loss after labilization of the enzyme. AB - Mechanism-based inactivation of cytochrome P450 can result in the chemical modification of the heme, the protein, or both as a result of covalent binding of modified heme to the protein. In the present study we took advantage of different modes of inactivation of P450 2E1 by CCl4, 1-aminobenzotriazole, or 3-amino-1,2,4 triazole to investigate parameters which target P450 2E1 for proteolysis from the microsomal membrane. Treatment of mice with CCl4 at the point of maximal induction of P450 2E1 after a single oral dose of acetone resulted in the complete loss of P450 2E1-dependent p-nitrophenol hydroxylation and a 75% loss of immunochemically detectable protein within 1 h of administration. Treatment with 1-aminobenzotriazole at the point of maximal induction caused a complete loss of P450 2E1-dependent p-nitrophenol hydroxylation but only a 12% loss of immunochemically detectable protein 1 h after administration. Treatment of mice with 3-amino-1,2,4-triazole caused a rapid loss of both catalytic activity and microsomal p-nitrophenol hydroxylase activity. However, unlike CCl4 treatment, the activity and enzyme level rebounded 5 and 9 h after treatment. The P450 2E1 ligand, 4-methylpyrazole, administered at the point of maximal induction maintained the acetone-induced catalytic and immunochemical level of P450 2E1. These results suggest that differentially modified forms of P450 2E1 show a characteristic susceptibility to degradation. While there are many potential pathways for protein degradation, the loss of P450 2E1 was associated with increased formation of high molecular weight microsomal ubiquitin conjugates. The formation of ubiquitin-conjugated microsomal protein which correlates with P450 2E1 loss suggests that ubiquitination may represent a proteolytic signal for the rapid and selective proteolysis of certain labilized conformations of P450 2E1 from the endoplasmic reticulum. PMID- 1309988 TI - Management strategies in resection for hilar cholangiocarcinoma. AB - Between 1960 and 1990, resection was performed in 23 of 122 patients who underwent surgical treatment for hilar cholangiocarcinoma. Local excision of the lesion alone was performed in 10 cases (43%). Hepatic resection for tumor extending to the secondary bile ducts or hepatic parenchyma was performed in 13 cases (57%): extended right hepatectomy (3), right hepatectomy (1), extended left hepatectomy (6), left hepatectomy (2), and left lobectectomy (1). In three other cases, resection by total hepatectomy and liver transplantation was performed, but these were not included in the analysis of results for resection. Significant operative complications occurred in only two cases (8.7%), and the operative mortality rate was zero. In four cases, complete excision of the tumor could not be achieved macroscopically (macroscopic curative resection rate 19/122; 15.6%). In nine cases, the margins of the resected specimens were free from tumor on histologic examination (microscopic curative resection rate, 9/122; 7.4%). In 10 cases, the resection margins were found to contain tumor on histologic examination. The overall survival rate was 87% at 1 year, 63% at 2 years, and 25% at 3 years (median survival, 24 months). The survival and freedom from recurrence rates for patients with free resection margins was superior to that for patients with involved resection margins or residual macroscopic disease. A potentially curative resection, with histologically negative margins and no recurrence to date, was achieved in seven patients using the following procedures: local excision for two type I lesions; left hepatectomy plus excision of segment 1 for two type IIIb lesions and one type IV lesion; right hepatectomy and right hepatectomy plus excision of segment 1 for two type IIIa lesions. These results indicate that improved survival in hilar cholangiocarcinoma can be achieved by resection, with minimal morbidity and zero mortality rates, if histologically free resection margins are obtained. To achieve this, we recommend the following procedures for each type of lesion, based on our experience and on anatomic considerations: local excision for type I; local excision plus resection of segment 1 for type II; local excision, resection of segment 1, and right or left hepatectomy for types IIIa and b; hepatectomy plus liver transplantation for type IV. PMID- 1309989 TI - Long-term results after colectomy and endorectal ileal pullthrough procedure in children. AB - Since 1987, 67 children with ulcerative colitis, 14 with colonic polyposis, and one with Hirschsprung's disease have undergone colectomy and endorectal ileal pullthrough procedures (ERP). Seventy-six children had a lateral ileal reservoir and six had a straight pullthrough. Seventy-seven patients had a diverting ileostomy for 4 months; five polyposis patients underwent ERP without ileostomy. Forty-three (52%) developed complications, including ileoanal stenosis with reservoir outlet obstruction (14), elongated ileal spout (2), elongated ileal reservoir greater than 15 cm (4), and a combination of outflow obstruction, reservoir enlargement causing stasis (14), and intestinal obstruction causing obstruction (10). Thirty-two children required reoperation. Sixty per cent of complications occurred in the first 30 patients. Only three of the last 40 patients had reoperation. There were no deaths. Four children (two with Crohn's disease) returned to a permanent ileostomy (4.9%); 10 had a temporary ileostomy. Five straight pullthroughs were converted to a reservoir because of stool frequency; 19 underwent reservoir reconstruction because of stasis. Seventy-five children (91.5%) are currently progressing very well. Features for optimal function include a short rectal muscle cuff, a short reservoir and spout, and aggressive correction of rectal strictures. The ERP is a desirable option to proctocolectomy and ileostomy for children with colitis or polyposis. PMID- 1309990 TI - Routine use of selective venous sampling for the localization of functioning islet cell tumors of the pancreas. PMID- 1309991 TI - Sclerosing hemangioma of the lung: radiographic and pathological study. AB - The clinical, radiographic, and pathological features of 10 patients with sclerosing hemangioma of the lung seen between 1974 and 1990 were reviewed. The incidence of sclerosing hemangioma was 22.2% of benign tumors surgically resected during that time. There were 2 male and 8 female patients aged 15 to 77 years at operation, and 9 patients were asymptomatic. All 10 patients had a solitary tumor with a well-defined homogeneous round or oval shadow on chest roentgenograms. Chest computed tomography revealed a homogeneous soft-density mass in 4 patients and a low-density portion within the tumor because of a cystic change in 1 patient. Microscopically, 5 patients had a preponderantly solid pattern, 3 had a preponderantly papillary pattern, and 1 patient had a preponderantly sclerotic pattern. One patient had an equal mixture of solid and papillary patterns. Nine of the 10 tumors consisted of a mixture of at least three of the four major patterns. Regarding treatment, thoracotomy is indicated for a definite diagnosis. If a benign tumor is suspected at operation, an intraoperative frozen section is recommended. Once the diagnosis has been established as sclerosing hemangioma, a limited resection is indicated. PMID- 1309992 TI - Lack of in vitro antiviral activity of fluoroquinolones against herpes simplex virus type 2. AB - The antiviral activity against herpes simplex virus type 2 (HSV-2) of five fluoroquinolones (ciprofloxacin, lomefloxacin, ofloxacin, pefloxacin, rufloxacin) was tested in vitro. Their efficacy was evaluated as reduction of the cytopathic effect (CPER) exerted by HSV-2 on Vero cells in comparison with novobiocin and acycloguanosine. Our results show a very poor antiviral effect of five quinolones (CPER50 = 200 mg/l) that was comparable with their cytotoxicity (TCIC50 less than 200 mg/l). Novobiocin shows a lower toxicity (TCIC50 = 400 mg/l) and a slight antiviral activity (CPER50 = 120 mg/l). Acycloguanosine shows a TCIC50 greater than 400 mg/l and a CPER50 of 3.125 mg/l. The therapeutic indices gave values ranging from 0.12 to 2 for quinolones, of 3.3 for novobiocin, and greater than 128 for acycloguanosine. The antiviral efficacy of acycloguanosine was not affected by concentrations of quinolones active against bacteria (1-10 mg/l) whereas it was drastically reduced by higher doses of quinolones (greater than 50 mg/l). Our data suggest that fluoroquinolones cannot be considered drugs able to inhibit HSV-2 replication in vitro. PMID- 1309993 TI - Isolation of mononuclear cytotoxic cells from cattle vaccinated against foot-and mouth disease. AB - Mononuclear cells from peripheral blood leucocytes of foot-and-mouth disease (FMD) vaccinated cattle underwent blast transformation after in vitro culture with purified, inactivated, 146 S FMD virus antigen. From the prolonged culture of blast cells in medium with Interleukin-2 (5-10 U/ml), CD 45-positive effector cells were derived, which showed a potent, non MHC-restricted activity against virus-infected cells, the extent of which was inversely correlated with multiplicity of infection (MOI). Extensive characterization of effector cells by means of monoclonal antibodies (MAbs) in flow cytometry, lysis of various cell populations with MAbs and complement, Fc receptor analysis and 51Cr release assays indicated that the isolated cells share some phenotypic and functional features of the human and murine Large Granular Lymphocyte/Natural Killer (N.K.) lineage. PMID- 1309995 TI - Early induction of DNA single-stranded breaks in cells infected by herpes simplex virus type 1. AB - In cells infected with herpesviruses a series of host-cell nuclear changes can be observed in a temporal sequence, such changes include chromosome aberrations. The precise mechanism by which virus infection produces chromosome damage is not known. Previous studies have revealed modifications in the properties of chromatin from infected cells, but such modifications are not due to extensive breakdown of host DNA or alteration of the nucleosomal structure in bulk host chromatin. We have adapted and modified a fluorescence enhancement assay for DNA damage in order to study the effects of herpes simplex virus type 1 infection on the integrity of the host-cell DNA. Here it is reported that HSV-1 induces a significant number of single-stranded breaks in the host-cell DNA at early hours post-infection. Such breaks seem not to be directly related to the major breakdown of host-cell DNA seen at later times post-infection. PMID- 1309994 TI - Coronavirus IBV-induced membrane fusion occurs at near-neutral pH. AB - The lysosomotropic agent NH4Cl caused a reduction of 80-95% in the number of chick kidney (CK) cells and Vero cells infected by infectious bronchitis virus (IBV) strain Beaudette, as determined by immunofluorescence at the end of the first replication cycle. Inhibition only occurred when NH4Cl was present during the first 2 h after infection. Syncytium formation was studied during replication of IBV-Beaudette in Vero cells. Some cell-cell fusion occurred at pH 7.0 and pH 6.5 but it was optimal at pH 6.7. IBV strain UK/123/82 did not replicate in Vero cells and was studied in CK cells in which it grew well but without forming syncytia. In contrast to IBV-Beaudette, NH4Cl had virtually no effect on the replication of UK/123/82. The results show that the IBV spike glycoprotein induces membrane fusion at near neutral pH although some IBV strains may require a mildly acidic environment for the efficient uncoating of the virion RNA. PMID- 1309996 TI - Latency of a thymidine kinase-negative pseudorabies vaccine virus detected by the polymerase chain reaction. AB - Latent viral DNA was detected by the polymerase chain reaction in trigeminal ganglia of all of 10 pigs that were necropsied 81 or more days after they had been infected intranasally with a thymidine kinase-negative (TK-) vaccine strain of pseudorabies virus (PRV). Failure to reactivate virus from any of the same pigs by earlier treatment with dexamethasone suggested that even though latency can be established with TK- PRV, subsequent reactivation may be a relatively rare event. PMID- 1309997 TI - Glycoprotein-specific immune response in canine herpesvirus infection. AB - Sera from dogs which were infected with canine herpesvirus (CHV) were analyzed for their serological reactivities against virus-specific glycoproteins (gps). By sequential immunoblot analysis using sera from experimentally infected dogs, it was found that the antibody response to gp 145/112 appeared first followed by responses to gp47 and gp80. In addition, all sera from naturally infected dogs which showed neutralizing activity to CHV reacted with gp 145/112, whereas 77% and 70% reacted with gp47 and gp80, respectively. Furthermore, some of the sera also cross-neutralized feline herpesvirus type 1 (FHV-1) and reacted with gp 143/108 of FHV-1, indicating that gp 145/112 of CHV induced cross-neutralizing antibody response to FHV-1. PMID- 1309998 TI - Hemagglutinin activity of two distinct genogroups of feline and canine rotavirus strains. AB - Genomes of hemagglutinating strains of feline and canine rotaviruses, were much more closely related to each other than to non-hemagglutinating strains. The Cat2 feline rotavirus appears to derive from reassortment between hemagglutinating and non-hemagglutinating strains. PMID- 1309999 TI - Expression of feline immunodeficiency virus gag gene in Escherichia coli. AB - The gag gene of a Japanese feline immunodeficiency virus (FIV) isolate, designated as FIV TM 2, was expressed in Escherichia coli as a fusion protein with TrpE. Using this expressed protein, an enzyme-linked immunosorbent assay was developed for detection of antibodies to FIV gag protein in feline sera. With serum samples from a cat experimentally infected with FIV, it was demonstrated that the period of seroconversion detected by this method corresponded to that by Western blotting. PMID- 1310000 TI - Coxsackievirus B3 from an infectious cDNA copy of the genome is cardiovirulent in mice. AB - A coxsackievirus B3 (CVB3) cDNA clone, upon transfection of HeLa cells, produces CVB3 capable of induction of cardiac inflammation in C3H/He mice by day 8 post inoculation (p.i.). Liver and serum are cleared of CVB3 by day 8 p.i., but CVB3 persists in the heart through day 14. The nucleotide sequence and the predicted amino acid sequence of this clone have sites of divergence from 2 other completely sequenced CVB3 genomes although overall identity of the three CVB3 genomes is 99%. PMID- 1310001 TI - Management and monitoring of cancer-associated retinopathy. AB - Cancer-associated retinopathy is a rare paraneoplastic event that can involve allergic reactions and result in retinal degradation. A patient, who had a 35 year smoking history, complained of visual loss and was found to have serum antibodies that reacted with an extract of retina, including the previously described retinal cancer-associated retinopathy antigen. Prednisone treatment appeared to reduce the patient's antibody titers to normal levels. Visual fields stabilized, and the patient was able to maintain useful vision throughout the course of treatment until his death 1 year following initial diagnosis. To our knowledge, this is the first reported case in which monitoring of antibody responses to retinal antigens appeared to be useful in the decision whether to initiate prednisone therapy. Rising antibody titers to the cancer-associated retinopathy antigen probably occurs before progressive visual field loss and may be considered an indication for prompt steroid therapy. PMID- 1310002 TI - Malignant fibrous histiocytoma in Paget's disease of bone. A report of seven cases. AB - Malignant change in Paget's disease of bone usually has the histological features of osteosarcoma, but follows a different clinical course from cases not associated with paget's disease of bone. Malignant fibrous histiocytoma is an uncommon neoplasm which may be associated with pagetic bone and its clinical course is not well defined. Seven cases of malignant fibrous histiocytoma in Paget's disease were reviewed from two Australian bone tumour registries. In stage IIB and III disease there was a three year survival rate of 57%, suggesting a better prognosis than for patients with other sarcomas in Paget's disease. PMID- 1310003 TI - Characterization of ligand binding and processing by gastrin-releasing peptide receptors in a small-cell lung cancer cell line. AB - The ligand-binding properties of the gastrin-releasing peptide (GRP) receptor and the cellular processing of GRP have been studied in the small-cell lung cancer (SCLC) cell line COR-L42. Scatchard analysis of GRP receptor expression indicated a single class of high-affinity receptors (Kd 1.5 nM) and approx. 6700 receptors/cell. GRP bound to its receptor with a Ki of 2.4 nM. The bombesin related peptides neuromedin B (NMB) and phyllolitorin also bound to GRP receptors with Ki values of 22.7 and 59.1 nM respectively. Binding of 125I-GRP to COR-L42 cells increased rapidly at 37 degrees, achieved a maximum at 10 min and declined rapidly thereafter. At 4 degrees C, maximum binding was achieved at 30 min and the subsequent decline in cell-associated radioactivity was slower than that seen at 37 degrees C. Acid/salt extraction, to separate surface-bound ligand from internalized GRP, indicated that after receptor binding 125I-GRP was rapidly internalized. To determine the pathway of 125I-GRP degradation, binding studies were carried out with the lysosomotropic agent chloroquine (5 mM), and with phosphoramidon (10 microM), an inhibitor of the membrane-bound enzyme (EC 3.4.24.11). Both agents markedly inhibited the degradation of GRP, indicating that this process involves a lysosomal pathway and a phosphoramidon-sensitive pathway, possibly involving the EC 3.4.24.11 enzyme. GRP receptor down-regulation was observed following a 10 min exposure to 100 nM-GRP. With longer pretreatment times the number of binding sites recovered to 80% of control values. Treatment with 5 mM-chloroquine plus GRP or cycloheximide (10 micrograms/ml) plus GRP demonstrated that the majority of GRP receptors are recycled. NMB and phyllolitorin pretreatment did not influence the subsequent binding of 125I-GRP, suggesting that these peptides do not down-regulate GRP receptors. PMID- 1310005 TI - Direct detection of a globin-derived radical in leghaemoglobin treated with peroxides. AB - The root nodules of leguminous plants contain an oxygen-carrying protein which is somewhat similar to myoglobin. Reaction of the Fe3+ form of this protein (metleghaemoglobin; MetLb) with H2O2 is known to generate a ferryl [iron(IV)-oxo] species. This intermediate, which is analogous to Compound II of peroxidases and ferryl myoglobin, is one oxidizing equivalent above the initial level. In the present study it is shown that the second oxidizing equivalent from the peroxide is rapidly transferred into the surrounding protein, generating a protein radical which has been detected by e.p.r. spectroscopy; this reaction is analogous to that observed with metmyoglobin. An identical protein-derived species is observed with all three forms of MetLb tested (a, c1, c3) and with a number of other hydroperoxides and two-electron oxidants. This latter result, the observation that the concentration of this species is not affected by certain hydroxyl radical scavengers, and the loss of the radical when the oxy or deoxy forms are used, demonstrate that this species is formed by electron transfer within the protein rather than by the generation and subsequent reaction of hydroxyl radicals (and related species from the other hydroperoxides). The e.p.r. signal of this species, which decays rapidly with a half-life of approx. 40 s, is consistent with the formation of a sterically constrained tyrosine-derived phenoxyl radical; protein-iodination experiments lend support to this assignment. Reaction between the radical and a number of other compounds has been observed, demonstrating that it is at least partially exposed on the surface of the protein. Analysis of the protein structure suggest that the radical may be centred on a tyrosine residue present at position 132 in the protein; this residue is close to the haem prosthetic group, which would facilitate rapid electron transfer. PMID- 1310004 TI - Synthesis and characterization of a high-affinity photoactivatable analogue of thyrotropin-releasing hormone. AB - An analogue of thyrotropin-releasing hormone (TRH, pGlu-His-ProNH2), i.e. pGlu His-ProNH-(CH2)6-(4-azidosalicylamide) (TRH-ASA), has been synthesized and, in a radioiodinated form (TRH-IASA), characterized and used as a photoaffinity reagent to label the TRH receptor on rat pituitary GH4C1 cells. TRH-IASA bound to GH4C1 cells with high affinity (Kd = 8 nM), comparable with that of TRH binding. The binding of TRH-IASA was competitive with binding of TRH, two TRH analogues and a TRH receptor antagonist, chlordiazepoxide. TRH-IASA did not bind to or label GH12C1 cells, which lack functional TRH receptors. Labelling of GH4C1 cells with TRH-IASA followed by SDS/PAGE and autoradiography of membrane proteins demonstrated labelling of a single polypeptide which ran as a diffuse band between 71 and 91 kDa, centred at 76 kDa. No change in this labelling pattern was observed as a function of the length of time (between 5 min and 2 h) that GH4C1 cells were incubated with 3 nM-TRH-IASA. Using either a very short (5 s) photolysis interval or low TRH-IASA concentrations, only the 76 kDa band was labelled. Minor bands appeared only after extended photolysis and use of high TRH IASA concentrations. We conclude that the TRH receptor from rat pituitary GH4C1 cells is a single peptide with an apparent molecular mass of 76 kDa. Details of the chemical synthesis of TRH-ASA are given in Supplementary Publication SUP 50167 (5 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1992) 281, 5. PMID- 1310006 TI - Simultaneous redistribution of mannose 6-phosphate and transferrin receptors by insulin-like growth factors and phorbol ester. AB - Insulin-like growth factors I and II (IGF-I and IGF-II) and phorbol ester are known to induce in fibroblasts a rapid redistribution of mannose 6-phosphate (M6P)/IGF II-receptors to the cell surface. We compared the redistribution of the M6P/IGF-II receptor with that of the 46 kDa M6P receptor (MPR46) and of receptors for transferrin, low-density lipoprotein (LDL) and epidermal growth factor (EGF) in human fibroblasts under the influence of these effectors. None of the effectors altered the surface expression of receptors for LDL or EGF, which are predominantly located at the cell surface. IGF-I, IGF-II and phorbol ester increased the surface expression of the M6P/IGF-II receptor and of MPR46. The concentration of the transferrin receptor at the cell surface was increased only by IGF-I and IGF-II, with similar kinetics as for the M6P/IGF-II receptor, suggesting that the same mechanism causes redistribution. The increased surface expression of M6P receptors was accompanied by an increased uptake of receptor ligands. The number of transferrin receptors did not correlate with iron uptake, although neither the rate nor the extent of transferrin internalization was changed. These results indicate that the redistribution of several endocytic receptors induced by IGF-I, IGF-II and phorbol ester shows selectivity, and that the uptake of receptor ligand may become uncoupled from the surface expression of the receptors via distinct mechanisms. PMID- 1310007 TI - Cytosolic pH regulation in mouse macrophages. Characteristics of HCO3(-) dependent mechanisms. AB - Mechanisms regulating cytosolic pH (pHi) in adherent resident mouse macrophages have been characterized by use of the pH-sensitive fluorescent probe 2',7' bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Na+/H+ exchange was activated after an acid load of the macrophage cytosol. However, when Na+/H+ exchange was the only pHi-regulatory mechanism operative, recovery did not proceed beyond a pHi of approx. 6.6. The mechanisms found to be operative at physiological pHi levels were alkalinizing Na(+)-dependent and acidifying Na(+)-independent Cl /HCO3- exchangers and a H(+)-ATPase further characterized in the accompanying paper [Tapper & Sundler (1992) Biochem. J. 281, 245-250]. Acid extrusion via Na+/Cl-/HCO3- exchange was demonstrated by the dependence on external Na+ and HCO3- and on internal Cl- and by the sensitivity to 4-acetamido-4' isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and 4,4'-di isothiocyanatostilbene-2,2'-disulphonic acid (DIDS). By monitoring pHi changes upon Cl- removal and re-addition, the pH-dependence and sensitivity to SITS were found to differ for the alkalinizing and the acidifying Cl-/HCO3- exchangers. PMID- 1310008 TI - Inositol polyphosphate metabolism and inositol lipids in a green alga, Chlamydomonas eugametos. AB - Swimming suspensions of Chlamydomonas eugametos were pelleted and homogenized, and the metabolism of inositol polyphosphates by cellular homogenates or supernatants was investigated. Ins(1,4,5)P3 was dephosphorylated under physiological conditions to yield a single InsP2, Ins(1,4]2. In the presence of ATP it was phosphorylated to give Ins(1,3,4,5)P3 as the only InsP4. The Ins(1,4,5)P3 3-kinase activity was predominantly soluble, was not detectably affected by calmodulin or Ca2+, and had a Km for Ins(1,4,5)P3 of 50 microM (two orders of magnitude higher than its mammalian counterpart). Ins(1,3,4,5)P4 was dephosphorylated by the cellular supernatants to Ins(1,3,4)P3 and Ins(1,4,5)P3, and could be phosphorylated to Ins(1,3,4,5,6)P4. No Ins(1,3,4)P3 6-kinase activity could be detected, and experiments with [3H]Ins(1,4,[32P]5)P3 revealed that Ins(1,3,4,5,6)P5 is formed from Ins(1,4,5)P3 with little loss of the 5 phosphate, i.e. the predominant route of synthesis is probably by a direct 6 phosphorylation of Ins(1,3,4,5)P4. Similar experiments with an (NH4)2SO4 fraction of turkey erythrocyte cytosol gave essentially the same result, i.e. direct phosphorylation of Ins(1,3,4,5)P4 in the 6 position is the predominant route of synthesis of InsP5 from that InsP4 in vitro. No InsP6 formation was detected in any of these experiments, but labelling of intact C. eugametos with [3H]inositol revealed that the cells do synthesize InsP6. The lipids of C. eugametos cells contain PtdIns, PtdIns(4)P and PtdIns(4,5)P2 [Irvine, Letcher, Lander, Drobak, Dawson & Musgrave (1989) Plant Physiol. 64, 888-892]. Further examination of 32P labelled lipids revealed that about 20% of the PtdInsP was the PtdIns(3)P isomer, and about 1% or less of the PtdInsP2 was the PtdIns(3,4)P2 isomer. The overall inositide metabolism of C. eugametos resembles that of a mammalian cell more closely than it does that of a plant cell or slime mould, and this suggests firstly that the known metabolism of inositol polyphosphates arose at an early time in eukaryotic evolution, and secondly that Chlamydomonas might prove a useful organism for genetic and comparative studies of inositide enzymology. PMID- 1310009 TI - Calmidazolium is a potent stimulator of steroidogenesis via mechanisms not involving cyclic AMP, calcium or protein synthesis. AB - This study reports an unexpected effect of calmidazolium on steroidogenesis. In contrast with previous work, which established that calmidazolium inhibits hormone-stimulated testosterone production in rat Leydig cells, the present study demonstrates that this compound is a potent stimulator of steroidogenesis when added by itself; this stimulation (approx. 10-fold in a 2 h incubation), was obtained over a narrow dose range (e.g.1-10 microM) in mouse and rat Leydig cells and in rat adrenocortical cells. The same concentrations of calmidazolium decreased basal cyclic AMP to undetectable levels in rat Leydig cells. Also, cyclic AMP stimulated with luteinizing hormone (LH), cholera toxin and forskolin was inhibited by calmidazolium (ED50 2 microM). In contrast with the actions of LH and cyclic AMP analogues on steroidogenesis, the effect of calmidazolium was not inhibited by removal of extracellular Ca2+, or by the addition of La3+ (a Ca(2+)-entry blocker), or the addition of cycloheximide (an inhibitor of protein translation). However, like dibutyryl cyclic AMP, calmidazolium-stimulated steroidogenesis was inhibited by aminoglutethimide, an inhibitor of cholesterol side-chain cleavage. Another calmodulin inhibitor, trifluoperazine, did not stimulate steroidogenesis. It is concluded that calmidazolium has a similar effect on steroidogenesis to LH, but by-passes the requirements for cyclic AMP, Ca2+, and protein synthesis. Calmidazolium is therefore a potentially important probe for elucidating the mechansims of control of steroidogenesis. PMID- 1310010 TI - Dual regulation of cyclic AMP formation by thrombin in HEL cells, a leukaemic cell line with megakaryocytic properties. AB - Thrombin is thought to stimulate responsive cells by cleaving cell-surface receptors coupled to intracellular second-messenger-generating enzymes via G proteins. In order to understand this process better, we have examined the regulation of adenylate cyclase by thrombin in the megakaryoblastic HEL cell line and compared it with platelets. A notable difference was found. In HEL-cell membrane preparations, thrombin inhibited cyclic AMP (cAMP) formation by a pertussis-toxin-sensitive mechanism comparable with that observed in platelets. In contrast, when added to intact HEL cells, thrombin activated adenylate cyclase and caused an increase in cAMP formation synergistic with that produced by forskolin and prostaglandin I2. This increase, which was not seen with platelets, was accompanied by an increase in cAMP metabolism by phosphodiesterase. Like other responses to thrombin, the increase in cAMP formation required proteolytically active thrombin and was subject to homologous desensitization. An equivalent response could be evoked by the addition of a polypeptide, derived from the N-terminus of the thrombin receptor, that has been shown to activate the receptor. The effects of thrombin could not, however, be reproduced by the addition of phorbol ester and the Ca2+ ionophore, A23187, nor be prevented with inhibitors of arachidonate metabolism. Preincubation of the cells with adrenaline, which inhibited Gs-mediated activation of adenylate cyclase, or pertussis toxin, which inhibited phospholipase C activation, had no effect on thrombin-induced cAMP formation. These results suggest that thrombin can regulate cAMP formation by two different mechanisms. First, thrombin can inhibit adenylate cyclase in a Gi-dependent manner. This effect predominates in HEL-cell membrane preparations, as it does in platelets, but is not detectable when thrombin is added to intact HEL cells. Instead, in intact HEL cells thrombin activates adenylate cyclase. Although clearly receptor-mediated, this response does not appear to involve Gi, Gs, protein kinase C, eicosanoid formation or changes in the cytosolic Ca2+ concentration. PMID- 1310011 TI - Characterization of protein kinase C in Xenopus oocytes. AB - Protein kinase C (PKC) was partially purified from Xenopus laevis oocytes by ammonium sulfate fractionation followed by DEAE-cellulose and hydroxyapatite column chromatography. In the latter chromatography, two distinct PKC activities were identified. Both PKC fractions contained an 80 kDa protein which was recognized by three antisera raised against the conserved regions of mammalian PKC. However, specific antisera against alpha, beta I, beta II, and gamma subspecies of rat PKC did not recognize the protein. Kinetic properties of the Xenopus PKCs were very similar to those of the rat alpha PKC, and only a subtle difference was found in the mode of activation by arachidonic acid. When oocytes were treated with the tumor promoter, phorbol 12-myristate 13-acetate, one of the Xenopus PKCs was found to disappear very rapidly, while the other remained unchanged up to 2 hr. PMID- 1310012 TI - The mechanism of activation of protein kinase FA (the activator of type-1 protein phosphatase) in brain synaptosomes. AB - The ATP.Mg-dependent type-1 protein phosphatase and its activating factor (protein kinase FA) were identified to exist in brain synaptosome. The inactive protein phosphatase was found to exist in the synaptosomal cytosol whereas its activating factor (protein kinase FA) was present in the synaptosomal membrane, indicating that the inactive protein phosphatase and its activating factor FA are localized in two separate subcellular compartments. The membrane-bound FA was found to exist in two forms; approximately 75% of FA is inactive and trypsin resistant, whereas 25% of FA is active and trypsin-labile. When membranes were incubated with exogenous phospholipase C, the inactive/trypsin-resistant FA could be activated and sequestered to become the active/trypsin-labile FA in a time- and dose-dependent manner. Taken together, the results provide initial evidence that the activation-sequestration of membrane-bound protein kinase FA may represent one mode of control modulating the activity of protein kinase FA and thereby to activate protein phosphatase in brain synaptosome, representing an efficient regulatory mechanism for regulating neurotransmission in the central nervous system. PMID- 1310013 TI - Different distribution of endothelin receptor subtypes in pulmonary tissues revealed by the novel selective ligands BQ-123 and [Ala1,3,11,15]ET-1. AB - We have demonstrated the different distribution of two distinct endothelin (ET) receptor subtypes in porcine pulmonary tissues using a radioligand binding assay. The clear differentiation of the subtypes was made possible by the discovery of two compounds, BQ-123 and [Ala1,3,11,15]ET-1 (4AlaET-1), that are highly selective for ETA and ETB receptors, respectively. In the bronchus and lung parenchyma, BQ-123 inhibited 65% and 30% of [125I]ET-1 binding on the sensitive sites, while 4AlaET-1 displaced 25% and 60%, respectively. The combination of the two compounds completely inhibited ET-1 binding in both tissues. An autoradiographic study of [125I]ET-1 binding using BQ-123 and 4AlaET-1 also supported the different localization of two ET receptor subtypes in pulmonary tissues. In particular, the blood vessels and bronchi are rich in ETA, but the lung parenchyma is rich in ETB. PMID- 1310014 TI - Spermine down-regulates superoxide generation induced by fMet-Leu-Phe in electropermeabilized human neutrophils. AB - Effect of spermine, a naturally occurring polyamine, was investigated on superoxide generation in intact and electropermeabilized human neutrophils. Spermine suppressed N-formyl-methionyl leucyl phenylalanine (fMLP)-induced superoxide generation in permeabilized cells by reducing the rate and shortening the duration time. The inhibition was specific for spermine comparing with its precursor amines, spermidine and putrescine. The inhibition was not observed when cells were preincubated with spermine without permeabilization. Concanavalin A induced superoxide generation was also down-regulated by spermine in permeabilized cells, but the activation induced by non receptor-mediated agonist (dioctanoylglycerol, phorbol myristate acetate, and arachidonate) was not affected by spermine. On the other hand, GTP-gamma-S-induced activation of superoxide generation was substantially suppressed by spermine. These results indicate that spermine inhibition occurs at a step prior to protein kinase C in signal transduction or in a pathway which is independent of the kinase. PMID- 1310015 TI - Identification of testis specific calcineurin beta subunit isoform by a monoclonal antibody and detection of a specific six amino acid sequence. AB - Two isoforms of calcineurin beta subunit(beta 1 and beta 2) were identified in rat testis by a monoclonal antibody Va1. Both beta 1 and beta 2 were recovered in calmodulin binding protein fraction and showed calcium shift on SDS polyacrylamide gel electrophoresis which is the specific character for EF-hand calcium binding protein. beta 2 showed same apparent molecular weight on SDS-PAGE as that of brain calcineurin beta and was found in wide variety of tissues. beta 1 was shown to have six amino acid polypepeptide sequence and it showed higher molecular weight than brain beta and was specific for testis. PMID- 1310016 TI - Tumor necrosis factor alpha inhibits the stimulatory effect of the parathyroid hormone-related protein on cyclic AMP formation in osteoblast-like cells via protein kinase C+. AB - Tumor necrosis factor alpha (TNF alpha) and parathyroid hormone-related protein (PTHrP) are both factors that have been implicated in the mechanism of hypercalcemia of malignancy. In this study we investigated the effect of TNF alpha on the PTHrP-stimulated accumulation of intracellular cyclic AMP in osteoblast-like cells. In the clonal cell line Saos-2 and in primary cell cultures from fetal rat calvaria, PTHrP-stimulated accumulation of cAMP was time- and dose-dependently inhibited by exposure to TNF alpha. Significant inhibition occurred at concentrations as low as 2 x 10(-12) M and was maximal at 1 x 10(-9) M. Inhibition was observed after 6 h and was maximal after 18 h. Inhibition by TNF alpha was probably mediated by protein kinase C, since the phorbol ester PMA mimicked the effect of TNF alpha, and the protein kinase C inhibitor H-7 completely abolished the effect of TNF alpha. In conclusion, these observations suggest a possible mechanism by which TNF alpha may modulate the effect of PTHrP on osteoblast function in the syndrome of humoral hypercalcemia of malignancy. PMID- 1310017 TI - Endothelin inhibits the atrial natriuretic factor stimulated cGMP production by activating the protein kinase C in rat aortic smooth muscle cells. AB - Preincubation of rat thoracic aortic smooth muscle cells with endothelin inhibits the atrial natriuretic factor (ANF)-induced cGMP accumulation in these cells in a concentration dependent manner. The maximal inhibition of 64% was afforded by 1 x 10(-6) M endothelin and the half maximal inhibition (IC50) was achieved with 1 x 10(-9) M endothelin. Endothelin (1 x 10(-6) M) also increased the plasma membrane bound protein kinase C (PKC) activity by 4 fold. Hormone-dependent increase in PKC activity was limited to plasma membranes only and some decrease in cytosolic PKC activity was observed. However, phorbol 12-myristate 13-acetate (PMA) (1 x 10(-6)M) provoked a total loss of cytosolic PKC activity and a net gain in membranous PKC activity indicative of the translocation of the enzyme. Pretreatment of these cells with H-7, a PKC inhibitor, released the endothelin and PMA-mediated attenuation of ANF-stimulated cGMP formation. These results suggest that PKC is involved in the regulation of ANF-induced cGMP accumulation and that the vasoconstrictor activity of endothelin might involve inhibition of the vasorelaxant activity of ANF through the inhibition of cGMP accumulation in smooth muscle cells (SMCs) of the rat aorta. PMID- 1310019 TI - Inhibition of endothelial cell clearance of atrial natriuretic peptide by cyclic GMP treatment. AB - In a previous study, we reported that cyclic GMP (cGMP) selectively down regulates the clearance receptor (C-receptor) for atrial natriuretic peptide (ANP) in the cultured bovine pulmonary artery endothelial (CPAE) cell line. The present study was undertaken in order to examine the effect of cGMP on the internalization of the ANP-receptor complex in CPAE cells. Maximum binding of [125I]APIII to the cells significantly decreased following the treatment with 1 mM 8-bromo-cGMP for 48 or 72 h. Scatchard analysis of the binding assay data from the treated cells showed a decrease in Bmax (616 to 411 fmol/mg protein) without a significant change in Kd. Removal of cell surface-bound APIII by acetic acid revealed that not only the surface binding, but also the internalization of APIII significantly decreased in 8-bromo-cGMP-treated cells, indicating a decrease in receptor-mediated uptake of ANP into the cells. These results suggest that cGMP regulates the clearance of ANP by vascular endothelial cells. PMID- 1310018 TI - Pituitary adenylate cyclase activating polypeptide provokes cultured rat chromaffin cells to secrete adrenaline. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) provoked the rat chromaffin cells to secrete adrenaline. Within 20 min, the amount of adrenaline secreted by PACAP (10(-8) M) was as much as that caused by acetylcholine (10(-4) M). PACAP, but not acetylcholine, induced a long-term (over 120 min) increase in secretion of adrenaline. PACAP also activated adenylate cyclase and elevated cytosolic Ca2+ concentration. Furthermore, we found immunoreactive PACAP and PACAP binding sites in the rat adrenal medulla. These results suggest that PACAP has an important role in stimulating secretion of adrenaline in the adrenal medulla. PMID- 1310020 TI - Suppressive effect of carbachol on forskolin-stimulated neurite outgrowth in human neuroblastoma NB-OK1 cells. AB - We have used human neuroblastoma NB-OK1 cells to investigate the regulation of neurite outgrowth. Carbachol suppressed forskolin-stimulated neurite outgrowth in NB-OK1 cells although forskolin-stimulated cAMP levels were enhanced. The dose response curve for this suppression was very similar to that for stimulation of inositol monophosphate (IP1) formation and for stimulation of the initial rise of [Ca2+]i elicited by carbachol. Carbachol-mediated changes in neurite outgrowth, IP1 formation and [Ca2+]i displayed high sensitivity for pirenzepine but low sensitivity for AF-DX116. Inhibition of intracellular calcium release with TMB-8 prevented the suppressive effect of carbachol on forskolin-stimulated neurite outgrowth. Hence we describe for the first time a relationship between neurite outgrowth and inositol triphosphate-triggered calcium release mediated by carbachol in the human neuron-derived cell line. PMID- 1310021 TI - Chemical cross-linking of the cytosolic and nuclear forms of the Ah receptor in hepatoma cell line 1c1c7. AB - Both cytosolic and high salt nuclear extracts were isolated from Hepa 1c1c7 cells incubated with 2-azido-3[125I]iodo-7,8-dibromo-dibenzo-p-dioxin ([125I]N3Br2DpD). The [125I]N3Br2DpD-labeled cytosolic fraction was subjected to chemical cross linking with dimethyl pimelimidate and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Chemical cross-linking of the cytosolic form of the AhR revealed monomeric (97 kDa), dimeric (185 kDa), trimeric (281 kDa), and tetrameric (327 kDa) complexes. In a time course of exposure to the cross-linking reagent, the largest form given above became the predominant AhR form observed in the cytosolic extracts. The 327 kDa cytosolic species apparently consists of a 97 kDa AhR, an approximately 88 kDa protein, an approximately 96 kDa protein, and an approximately 46 kDa protein. Nuclear extracts from [125I]N3Br2DpD-labeled Hepa 1c1c7 cells were applied to sucrose density gradients. The 6 S nuclear receptor peak fractions were pooled and subjected to chemical cross-linking. Analysis by SDS-PAGE revealed a monomeric (97 kDa) ligand binding protein and a dimeric (182 kDa) complex. This would suggest that the nuclear 6 S AhR consists of a 97 kDa AhR and an approximately 85 kDa protein. These findings would indicate that the AhR exists in cytosol as a tetrameric species, while in the nucleus the AhR exists as a heterodimer. PMID- 1310022 TI - The B cell repertoire in rheumatoid arthritis. III. Preferential homing of rheumatoid factor-producing B cell precursors in the synovial fluid. AB - OBJECTIVE: We sought to compare the frequencies of precursors producing IgM rheumatoid factors (IgM-RFs) in synovial fluid and peripheral blood B cells from patients with rheumatoid arthritis (RA). METHODS: We used limiting-dilution analysis of Epstein-Barr virus-activated B cells from seropositive and seronegative patients. B cell precursors producing IgM against insulin, an irrelevant autoantigen, were also assessed for comparison. RESULTS: On average, IgM-RF-producing precursors were 15-fold higher in the synovial fluid than in the peripheral blood of seropositive RA patients, but not in seronegative RA patients. The frequency of B cell precursors producing IgM against insulin was lower in the synovial fluid than in the peripheral blood of both the seropositive and the seronegative patient groups; moreover, the concentrations were similar in both groups. CONCLUSION: The findings provide evidence against a nonspecific accumulation of IgM-producing cells in the synovial fluid, and suggest that there is an active attraction of the RF-producing B cell precursors toward sites of inflammation in RA. PMID- 1310023 TI - [Cerebral lactate and pyruvate metabolism in infantile spasms]. PMID- 1310024 TI - Hypertriglyceridemia and regulation of fibrinolytic activity. AB - A relation between elevated triglyceride (TG) levels and alterations of the fibrinolytic system has been recognized in studies of patients with coronary heart disease. In this investigation, the total fibrinolytic activity and the levels of specific components of the fibrinolytic system were evaluated in plasma samples from a highly selected group of patients with type IV hyperlipoproteinemia before and after a dietary treatment aimed at reducing TG levels. The fibrinolytic response of type IV patients was comparable to that of normolipidemic subjects, whereas tissue-type plasminogen activator antigen levels before and after venous occlusion (p less than 0.01) and resting plasminogen activator inhibitor-1 (PAI-1) antigen (p less than 0.01) and activity (p less than 0.01) were significantly higher in hypertriglyceridemic subjects compared with controls. After dietary treatment, a 22% reduction in TG levels was attained in type IV patients, with no appreciable modification of fibrinolytic parameters. The analysis of the single-patient data revealed a tendency toward normalization of PAI-1 levels only in those patients who showed a TG reduction greater than or equal to 20%. Very low density lipoproteins (VLDLs) from both normal and type IV patients concentration-dependently stimulated PAI-1 release by endothelial cells and HepG2 cells, with the effect of VLDL from type IV patients being more pronounced on HepG2 cells. The release of PAI-1 induced by VLDL in competent cells may thus account for the elevated levels of this antifibrinolytic protein that occur in hypertriglyceridemic patients. PMID- 1310025 TI - Impaired vasodilatory response to atrial natriuretic peptide during atherosclerosis progression. AB - This study was undertaken to examine the alterations in vascular relaxation responsiveness to endothelium-dependent or -independent vasodilators, including atrial natriuretic peptide (ANP) and acetylcholine, in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits during the progression of the atherosclerotic plaque. WHHL rabbits were divided into two groups according to age: group 1, 6-11 months, and group 2, 12-18 months. The isolated thoracic aortas obtained from both normal (control) and WHHL rabbits were suspended in a bath containing oxygenated Krebs' buffer for recording of isometric force. The endothelium-dependent relaxation evoked by acetylcholine was reduced in group 1 WHHL rabbits and decreased progressively in proportion to the degree of atherosclerosis progression when compared with age-matched control rabbits. ANP induced relaxation was not significantly decreased in group 1 WHHL rabbits. However, ANP-induced relaxation was markedly impaired in group 2 WHHL rabbits. Thoracic aortas with severe atherosclerosis were less sensitive to ANP, with a significant increase in the median effective dose, although maximum relaxation induced by ANP was not reduced. Accumulation of cyclic GMP induced by ANP and acetylcholine was markedly reduced in atherosclerotic arteries obtained from group 2 WHHL rabbits compared with control rabbits. Vascular relaxation elicited by nitroglycerin or isoproterenol was not significantly impaired in atherosclerotic arteries from either group 1 or group 2 WHHL rabbits. From these results, we suggest that ANP-induced cyclic GMP formation and vascular relaxation via particulate guanylate cyclase in vascular smooth muscle cells are impaired in severely atherosclerotic arteries. PMID- 1310026 TI - Affinity purification of functional receptors for Escherichia coli heat-stable enterotoxin from rat intestine. AB - Active receptors for Escherichia coli heat-stable enterotoxin (ST) were partially purified by ligand-affinity chromatography. The affinity column was prepared by coupling ST to biotin derivatized with an extended N-hydroxysuccinylated spacer arm prior to binding to monomeric avidin immobilized on agarose. Detergent extracts of rat intestinal mucosa membranes were quantitatively depleted of ST binding activity when chromatographed on this affinity matrix. Biotinylated ST receptor complexes were eluted from affinity columns with 2 mM biotin and these complexes quantitatively dissociated with bile salts. Using this technique, functional ST receptors were purified maximally about 2000-fold, with about 3% of the total activity in crude extracts recovered in these purified preparations. Analysis of affinity-purified preparations by polyacrylamide gel electrophoresis and silver staining demonstrated a major protein subunit of 74 kDa. Affinity cross-linking of these preparations to 125I-ST demonstrated specific labeling predominantly of the 74-kDa subunit. In addition, lower amounts of labeled ST were incorporated into subunits of 164 and 45 kDa, confirming the heterogeneous nature of ST receptors. Purified receptors bound ST in a concentration-dependent fashion, with an IC50 of 10(-9) M. These studies demonstrate that ligand-affinity chromatography can be employed to purify ST receptors. The availability of purified receptors will facilitate further studies of mechanisms underlying ST induced intestinal secretion. PMID- 1310027 TI - Protein kinase A dependent membrane protein phosphorylation and chloride conductance in endosomal vesicles from kidney cortex. AB - Regulation of Cl conductance by protein kinase A may play a role in control of endosomal acidification [Bae, H.-R., & Verkman, A. S. (1990) Nature, 348, 637 639]. To investigate the mechanism of kinase A action, cell-free measurements of Cl transport and membrane protein phosphorylation were carried out in apical endocytic vesicles from rabbit kidney proximal tubule. Cl transport was measured by a stopped-flow quenching assay in endosomes labeled in vivo with the fluorescent Cl indicator 6-methoxy-N-(3-sulfopropyl)quinolinium. Phosphorylation was studied in a purified endosomal preparation by SDS-PAGE and autoradiography of membrane proteins labeled by [gamma-32P]ATP. Endosomes had a permeability (PCl) for conductive Cl transport of 3.1 x 10(-8) cm/s at 23 degrees C which was stilbene inhibitable. PCl was increased by 90 +/- 20% by a 10-min preincubation with the catalytic subunit of kinase A (PKA, 10 units/mL) and MgATP (0.5 mM) with anion selectivity Cl greater than I greater than Br. The increase in PCl was blocked by 100 microM N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) and was reversed by addition of alkaline phosphatase (AP, 40 units/mL) after incubation with PKA and MgATP; the increase in PCl was not blocked by pretreatment with AP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310028 TI - Redox-dependent changes in beta-extended chain and turn structures of cytochrome c in water solution determined by second derivative amide I infrared spectra. AB - The redox-dependent changes in secondary structure of cytochromes c from horse, cow, and dog hearts in water at 20 degrees C have been determined by amide I infrared spectroscopy. Second derivative amide I spectra were obtained by use of a procedure that includes a convenient method for the effective subtraction of the spectrum of water vapor in the system. The band at 1657 cm-1 representing the helix structure was unaffected by a change in redox state whereas changes in bands due to turns at 1680, 1672, and 1666 cm-1, unordered structure at 1650 cm 1, and beta-structures at 1632 and 1627 cm-1 occurred. About one-fourth of the beta-extended chain spectral region and one-fifth of the beta-turn region (involving a total of approximately 9-13 residues) were sensitive to the oxidation state of heme iron. No significant changes in the secondary structure of either the reduced or oxidized protein due to changes in ionic strength were detected. The localized structural rearrangements triggered by the changes in oxidation state of heme iron are consistent with differences in the binding of heme iron to a histidine imidazole nitrogen and a methionine sulfur atom from the beta-extended chain. The demonstrated ability to obtain highly reproducible second derivative amide I infrared spectra confirms the unique utility of such spectral measurements for localization of subtle changes in secondary structure within a protein, especially for changes among the multiple turns and beta structures. PMID- 1310029 TI - Electron spin echo envelope modulation spectroscopic study of iron-nitrogen interactions in myoglobin hydroxide and Fe(III) tetraphenylporphyrin models. AB - The electron-nuclear coupling in low-spin iron complexes including myoglobin hydroxide (MbOH) and two related model compounds, Fe(III) tetraphenylporphyrin(pyridine)(OR-) (R = H or CH3) and Fe(III) tetraphenylporphyrin(butylamine)(OR-) was investigated using electron spin echo envelope modulation (ESEEM) spectroscopy. The assignment of frequency components in ESEEM spectra was accomplished through the use of nitrogen isotopic substitution wherever necessary. For example, the proximal imidazole coupling in MbOH was investigated without interference from the contributions of porphyrin 14N nuclei after substitution of the heme in native Mb with 15N-labeled heme. Computer simulation of spectra using angle selected techniques enabled the assignment of parameters describing the hyperfine and quadrupole interactions for axially bound nitrogen of imidazole in MbOH, of axial pyridine and butylamine in the models, and for the porphyrin nitrogens of the heme in native MbOH. The isotropic component of axial nitrogen hyperfine interactions exhibits a trend from 5 to 4 MHz, with imidazole (MbOH) greater than pyridine greater than amine. The nuclear quadrupole interaction coupling constant e2Qq was near 2 MHz for all nitrogens in these complexes. The Qzz axis of the nuclear quadrupole interaction tensor for the proximal imidazole nitrogen in MbOH was found to be aligned near gz (gmax) in MbOH, suggesting that gz is near the heme normal. A crystal field analysis, that allows a calculation of rhombic and axial splittings for the d orbitals of the t2g set in a low-spin heme complex, based on the g tensor assignment gz greater than gy greater than gx, yielded results that are consistent with the poor pi-acceptor properties expected for the closed shell oxygen atom of the hydroxide ligand in MbOH. A discussion is presented of the unusual results reported in a linear electric field effect in EPR (LEFE) study of MbOH published previously [Mims, W. B., & Peisach, J. (1976) J. Chem. Phys. 64, 1074-1091]. PMID- 1310030 TI - Mapping global angular transitions of proteins in assemblies using multiple extrinsic reporter groups. AB - The fluorescence polarization intensities from fluorescent probes and the electron paramagnetic resonance spectra from spin probes, specifically modifying elements of a biological assembly such as myosin sulfhydryl 1 (SH1) in muscle fibers, are interpreted in terms of probe order parameters using a model independent method. The probe order parameters are related to each other by an Euler rotation of coordinates. We use this relationship to link the sets of order parameters from the different probes and in so doing create a system of equations that can be solved using only the information available from the experimental data. The solution yields the Euler angles relating the different probe coordinate frames and a larger set of probe order parameters than can be directly detected experimentally. The Euler angles are used to display the relative orientation of the probe molecular frames. The order parameters give rise to probe angular distributions that are at the theoretical limit of resolution. We demonstrate the utility of this analytical method by investigating the rotation of myosin SH1 from its orientation in rigor upon the binding of the nucleotide MgADP to the myosin cross-bridge. Our findings, discussed in the accompanying paper, suggest that the rigor-to-MgADP cross-bridge angular transition consists predominantly of a rotation about the hydrodynamic axis of symmetry of the cross bridge, i.e., its torsional degree of freedom [Ajtai, K., Ringler, A., & Burghardt, T. P. (1992) Biochemistry (following paper in this issue)]. PMID- 1310031 TI - Probing cross-bridge angular transitions using multiple extrinsic reporter groups. AB - 15N- and 2H-substituted maleimido-TEMPO spin label ([15N,2H]MTSL) and the fluorescent label 1,5-IAEDANS were used to specifically modify sulfhydryl 1 of myosin to study the orientation of myosin cross-bridges in skeletal muscle fibers. The electron paramagnetic resonance (EPR) spectrum from muscle fibers decorated with labeled myosin subfragment 1 ([15N,2H]MTSL-S1) or the fluorescence polarization spectrum from fibers directly labeled with 1,5-IAEDANS was measured from fibers in various physiological conditions. The EPR spectra from fibers with the fiber axis oriented at 90 degrees to the Zeeman field show a clear spectral shift from the rigor spectrum when the myosin cross-bridge binds MgADP. This shift is attributable to a change in the torsion angle of the spin probe from cross-bridge rotation and is observable due mainly to the improved angular resolution of the substituted probe. The EPR data from [15N,2H]MTSL-S1 decorating fibers are combined with the fluorescence polarization data from the 1,5-IAEDANS labeled fibers to map the global angular transition of the labeled cross-bridges due to nucleotide binding by an analytical method described in the accompanying paper [Burghardt, T. P., & Ajtai, K. (1992) Biochemistry (preceding paper in this issue)]. We find that the spin and fluorescent probes are quantitatively consistent in the finding that the actin-bound cross-bridge rotates through a large angle upon binding MgADP. We also find that, if the shape of the cross bridge is described as an ellipsoid with two equivalent minor axes, then cross bridge rotation takes place mainly about an axis parallel to the major axis of the ellipsoid. This type of rotation may imitate the rotation motion of cross bridges during force generation. PMID- 1310032 TI - Circular DNA molecules imaged in air by scanning force microscopy. AB - Routine and reproducible imaging of DNA molecules in air with the scanning force microscope (SFM) has been accomplished. Circular molecules of plasmid DNA were deposited onto red mica and imaged under various relative humidities. In related experiments, the first images of the Escherichia coli RNA polymerase-DNA complex have also been obtained. This has been possible by (1) the use of specially modified SFM tips with a consistent radius of curvature of 10 nm or less, to minimize the amount of image distortion introduced by the finite dimensions of commercially available tips, (2) the optimization of a method to deposit and bind DNA molecules to the mica surface in a stable fashion, and (3) careful control of the sample humidity, to prevent solvation of the molecules and detachment from the surface by the scanning tip or stylus. Contact forces in the range of a few nanonewtons are routinely possible in air and in the presence of residual humidity. The spatial resolution of the images appears determined by the radius of curvature of the modified styli, which can be estimated directly from the apparent widths of the DNA molecules in the images. PMID- 1310033 TI - Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4 A resolution. AB - The crystal structure of the kringle 2 domain of tissue plasminogen activator was determined and refined at a resolution of 2.43 A. The overall fold of the molecule is similar to that of prothrombin kringle 1 and plasminogen kringle 4; however, there are differences in the lysine binding pocket, and two looping regions, which include insertions in kringle 2, take on very different conformations. Based on a comparison of the overall structural homology between kringle 2 and kringle 4, a new sequence alignment for kringle domains is proposed that results in a division of kringle domains into two groups, consistent with their proposed evolutionary relation. The crystal structure shows a strong interaction between a lysine residue of one molecule and the lysine/fibrin binding pocket of a noncrystallographically related neighbor. This interaction represents a good model of a bound protein ligand and is the first such ligand that has been observed in a kringle binding pocket. The structure shows an intricate network of interactions both among the binding pocket residues and between binding pocket residues and the lysine ligand. A lysine side chain is identified as the positively charged group positioned to interact with the carboxylate of lysine and lysine analogue ligands. In addition, a chloride ion is located in the kringle-kringle interface and contributes to the observed interaction between kringle molecules. PMID- 1310034 TI - A substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase. AB - Reduction of copper amine oxidase with substrate led to the appearance of a free radical which can be detected in anaerobiosis by ESR and optical spectroscopy. The origin of this radical was examined through studies of the semiquinones of 6 hydroxydopamine, an analogue of the recently identified cofactor 6-hydroxydopa. The ESR spectrum of the 6-hydroxydopamine radical was too narrow to account for the enzyme radical signal; however, after spontaneous reaction with primary amines the hyperfine splittings and spectral width obtained by modulation broadening became very similar to those observed for the oxidase radical species. This effect was ascribed to covalent binding of a nitrogen atom directly to the aromatic ring structure, suggesting that the amine oxidase radical is an amino-6 hydroxydopa semiquinone. Identical ESR spectra were obtained using the amines putrescine, cadaverine, p-[(dimethylamino)methyl]benzylamine, and ethylenediamine; these oxidase substrates gave identical enzyme radical spectra as well. The interaction between cofactor and substrate was proved unambiguously by the technique of isotopic labeling: addition of [15N2]ethylenediamine instead of the normal 14N-labeled compound changed the ESR spectra of both the enzyme radical and its 6-hydroxydopamine counterpart. The results were confirmed by optical spectroscopy measurements; 6-hydroxydopamine and oxidized 6 hydroxydopamine gave spectra identical to those of reduced and oxidized amine oxidase, respectively. The 6-hydroxydopamine radical showed a sharp peak at 440 nm; upon addition of amines the maximum shifted to 460 nm, as found for the enzyme. It is proposed that copper amine oxidase represents the first example of a mixed substrate-cofactor radical within the family of tyrosine radical enzymes. PMID- 1310035 TI - Metal activation of synthetic and degradative activities of phi 29 DNA polymerase, a model enzyme for protein-primed DNA replication. AB - Analysis of metal activation on the synthetic and degradative activities of phi 29 DNA polymerase was carried out in comparison with T4 DNA polymerase and Escherichia coli DNA polymerase I (Klenow fragment). In the three DNA polymerases studied, both the polymerization and the 3'----5' exonuclease activity had clear differences in their metal ion requirements. The results obtained support the existence of independent metal binding sites for the synthetic and degradative activities of phi 29 DNA polymerase, according with the distant location of catalytic domains (N-terminal for the 3'----5' exonuclease and C-terminal for DNA polymerization) proposed for both Klenow fragment and phi 29 DNA polymerase. Furthermore, DNA competition experiments using phi 29 DNA polymerase suggested that the main differences observed in the metal usage to activate polymerization may be the consequence of metal-induced changes in the enzyme-DNA interactions, whose strength distinguishes processive and nonprocessive DNA polymerases. Interestingly, the initiation of DNA polymerization using a protein as a primer, a special synthetic activity carried out by phi 29 DNA polymerase, exhibited a strong preference for Mn2+ as metal activator. The molecular basis for this preference is mainly the result of a large increase in the affinity for dATP. PMID- 1310036 TI - Growth state and cell cycle dependent phosphorylation of DNA topoisomerase II in Swiss 3T3 cells. AB - We have investigated the amount of DNA topoisomerase II and phosphorylation of the enzyme in Swiss 3T3 cells during the transition from cell quiescence to proliferation. A relatively high level of phosphorylation was observed with proliferating cells while no or a very low level of phosphorylation was observed with quiescent cells. Phosphoamino acid analysis of the phosphorylated topoisomerase II revealed that the phosphorylated aminoacyl residue was serine. When quiescent cells were stimulated to grow by the addition of serum, DNA synthesis began to increase at 9 h after serum addition, reaching a maximum at 15 h and then declining. The amount of topoisomerase II began to increase at 6 h and reached a maximum at 22-27 h, corresponding to the G2 phase. The phosphorylation of topoisomerase II measured by pulse-labeling gradually increased from 6 to 18 h and reached a maximum at 22 h when the amount of the enzyme was maximum. The level of phosphorylation measured by continuous-labeling increased gradually up to 12 h and markedly up to 28 h, and then declined. The increase in the rate of phosphorylation in the G2 phase was affected by inhibiting DNA synthesis, but the increase in the amount of the enzyme was not. Thus, it was suggested that the regulation of phosphorylation of topoisomerase II differs from that of the amount of the enzyme. PMID- 1310037 TI - Regulation of the calcium ion pump of sarcoplasmic reticulum: reversible inhibition by phospholamban and by the calmodulin binding domain of the plasma membrane calcium ion pump. AB - A 45 amino acid peptide (A45) corresponding to the phospholamban (PLN) binding domain of the sarcoplasmic reticulum (SR) ATPase was synthesized. Circular dichroism experiments have shown that the peptide had a predominantly random-coil conformation but adopted a higher proportion of secondary structure in the presence of a synthetic 32 amino acid peptide corresponding to the hydrophilic portion of PLN. A similar conformational change was induced by the synthetic calmodulin binding domain of the plasma membrane Ca2+ pump (peptide C28W), which acts as an endogenous inhibitor of the pump and is homologous to PLN. Cross linking experiments have shown that peptide C28W interacted with peptide A45. The Ca(2+)-pumping activity of cardiac SR, which contains endogenous PLN, was stimulated about 30% by peptide A45. The stimulation was maximal at submicromolar Ca2+ levels and tended to disappear at higher Ca2+ concentrations. By contrast, the Ca(2+)-pumping activity of skeletal muscle SR, which lacks endogenous PLN, was unaffected. Peptide C28W strongly inhibited the pumping activity of skeletal muscle SR, and peptide A45 reversed the inhibition. The results suggest that peptide A45 competed with the ATPase for phospholamban or for peptide C28W, removing the inhibition of the pump. Thus, the exogenous inhibitor of the SR Ca(2+)-ATPase, PLN, and the internal inhibitor of the plasma membrane Ca(2+) ATPase, peptide C28W, are functionally analogous. PMID- 1310038 TI - Mutations Pro----Ala-35 and Tyr----Phe-75 of Rhodobacter capsulatus ferrocytochrome c2 affect protein backbone dynamics: measurements of individual amide proton exchange rate constants by 1H-15N HMQC spectroscopy. AB - Comparisons of hydrogen-deuterium solvent exchange rate constants for the NH protons of wild-type Pro----Ala-35 (P35A) and Tyr----Phe-75 (Y75F) Rhodobacter capsulatus ferrocytochromes c2 were made by 1H-15N heteronuclear multiple-quantum correlation spectroscopy. Exchange rate constants increased for the NH protons of residues 45-46, 54, 57-58, 60-61, 82-87, 98, and 100 with Y75F and 16-18, 20, 34, 37, 43, 45-46, and 58 with P35A. The increases in exchange rate constants are consistent with changes in unfolding equilibria and protein dynamics. In Y75F the exchange rate constants of the observable NH protons of the helix spanning Pro-79 Asp-89, namely Phe-82-Leu-87, increase to a similar degree, suggesting that this helix is a single cooperative unfolding unit compatible with the local unfolding model. As the oxidation-reduction potential of Y75F is 59 mV lower than wild-type cytochrome c2 (367 mV), the dynamic changes in this mutant, compared to wild type, are proposed to be important determinants of the oxidation-reduction potential. Several differences between wild-type and Y75F are in common with P35A, a mutation which does not affect the oxidation-reduction potential, implying that not all observed dynamic changes are functionally important. PMID- 1310039 TI - Proton NMR study of the interaction of tin(IV) protoporphyrin IX monomers and dimers with apomyoglobin. AB - Events during the reconstitution of apomyoglobin to form the holoprotein were probed by porphyrin-metal substitution. Thus interactions between tin(IV) protoporphyrin IX (SnPP) and equine apomyoglobin (apoEqMb), and between tin(IV) protoporphyrin IX dimers [(SnPP)2] and apoEqMb, were observed by 1H NMR and optical absorbance spectroscopic techniques. The chief advantages of using SnPP are that products and intermediates can easily be related to SnPP.EqMb which has been studied [Deeb, R.S., & Peyton, D.H. (1991) J. Biol. Chem. 266, 3728-3733] and that at least one step during reconstitution is slowed considerably as compared to heme. Reactions of apoEqMb with SnPP and (SnPP)2 produce different intermediates, although the final product, SnPP.EqMb, is the same for each. An intermediate observed for reaction of SnPP with apoEqMb at pH 10 is in exchange with free SnPP, with the observed rate constant koff approximately 1 s-1. meso Proton resonances were assigned for this intermediate by correlation to SnPP resonances via chemical exchange. The intermediate observed for reaction of (SnPP)2 with apoEqMb at pH 7.5 is heterogeneous. The reaction of either SnPP or (SnPP)2 with apoEqMb at neutral pH produces another species which may be the alternate porphyrin-insertion isomer arising from a 180 degree rotation about the alpha, gamma-meso axis of the porphyrin. Although optical absorbance spectroscopy of the Soret region shows evidence for each reaction, only in combination with 1H NMR are the various processes assigned. PMID- 1310040 TI - Using saturation-recovery EPR to measure distances in proteins: applications to photosystem II. AB - The stable tyrosine radical YD. (tyrosine 160 in the D2 polypeptide) in photosystem II (PSII) exhibits nonexponential electron spin-lattice relaxation transients at low temperature. As previously reported, the tetranuclear Mn complex in PSII significantly enhances the spin-lattice relaxation of YD.. However, in Mn-depleted PSII membranes, the spin-lattice relaxation transients of YD. are also nonexponential, and progressive power saturation (P 1/2) experiments show that it does not behave like an isolated tyrosine radical. A model is developed to treat the interaction of two paramagnets in a rigid lattice at a fixed distance apart but with a random orientation in a magnetic field. This model describes the spin-lattice relaxation of a radical in proximity to another paramagnetic site in terms of three relaxation rate constants: the "intrinsic" relaxation rate, the relaxation rate due to scalar exchange, and the relaxation rate due to dipole-dipole interactions. The intrinsic and the scalar exchange relaxation rates are isotropic and together contribute a single rate constant to the spin-lattice relaxation transients. However, the dipolar relaxation rate is orientation dependent. Each orientation contributes a different dipolar relaxation rate constant to the net spin-lattice relaxation rate constant. The result is a superposition of single-exponential recoveries, each with a different net rate constant, causing the observed saturation-recovery transients to be non (single)-exponential. Saturation-recovery relaxation transients of YD. are compared with those of a model tyrosine radical, generated by UV photolysis of L tyrosine in a borate glass. From this comparison, we conclude that scalar exchange does not make a significant contribution to the spin-lattice relaxation of YD. in Mn-depleted PSII. We account for the nonexponential relaxation transients obtained from YD. in Mn-depleted PSII membranes in terms of dipolar induced relaxation enhancement from the non-heme Fe(II). From simulations of the spin-lattice relaxation transients, we obtain the magnitude of the magnetic dipolar interaction between YD. and the non-heme Fe(II), which can be used to calculate the distance between them. Using data on the non-heme Fe(II) in the reaction center of Rhodobacter sphaeroides to model the non-heme Fe(II) in PSII, we calculate a YD.-Fe(II) distance of greater than or equal to 38 A in PSII. This agrees well with the distance predicted from the structure of the bacterial reaction center. PMID- 1310041 TI - The manganese site of the photosynthetic oxygen-evolving complex probed by EPR spectroscopy of oriented photosystem II membranes: the g = 4 and g = 2 multiline signals. AB - The g = 4 and g = 2 multiline EPR signals arising from the Mn cluster of the photosynthetic oxygen-evolving complex (OEC) in the S2 state were studied in preparations of oriented photosystem II (PSII) membranes. The ammonia-modified forms of these two signals were also examined. The g = 4 signal obtained in oriented PSII membranes treated with NH4Cl at pH 7.5 displays at least 16 partially resolved Mn hyperfine transitions with a regular spacing of 36 G [Kim, D.H., Britt, R.D., Klein, M.P., & Sauer, K. (1990) J. Am. Chem. Soc. 112, 9389 9391]. The observation of this g = 4 "multiline signal" provides strong spectral evidence for a tetranuclear Mn origin for the g = 4 signal and is strongly suggestive of a model in which different spin state configurations of a single exchange-coupled Mn cluster give rise to the g = 4 and g = 2 multiline signals. A simulation shows the observed spectrum to be consistent with an S = 3/2 or S = 5/2 state of a tetranuclear Mn complex. The resolution of hyperfine structure on the NH3-modified g = 4 signal is strongly dependent on sample orientation, with no resolved hyperfine structure when the membrane normal is oriented perpendicular to the applied magnetic field. The dramatic NH3-induced changes in the g = 4 signal resolved in the spectra of oriented samples are suggestive that NH3 binding at the Cl- site of the OEC may represent direct coordination of NH3 to the Mn cluster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310042 TI - Antagonistic and synergistic peptide analogues of the tridecapeptide mating pheromone of Saccharomyces cerevisiae. AB - Biologically inactive, truncated analogues of the Saccharomyces cerevisiae alpha mating factor (WHWLQLKPGQPMY) either antagonized or synergized the activity of the native pheromone. An amino-terminal truncated pheromone [WLQLKPGQP(Nle)Y] had no activity by itself, but the analogue acted as an antagonist by competing with binding and activity of the mating factor. In contrast, a carboxyl-terminal truncated pheromone [WHWLQLKPGQP] was not active by itself nor did the peptide compete with alpha-factor for binding to the alpha-factor receptor, but it acted as a synergist by causing a marked increase in the activity of alpha-factor. The observation that residues near the amino terminus may be involved in signal transduction whereas those near the carboxyl terminus influence binding allows us to separate binding and signal transduction in the yeast pheromone response pathway. If found for other hormone-receptor systems, synergists may have potential as therapeutic compounds. PMID- 1310043 TI - Rotational motion of monomeric and dimeric immunoglobulin E-receptor complexes. AB - Erythrosin 5'-thiosemicarbazide labeled immunoglobulin E (IgE) was used to monitor the rotational dynamics of monomeric and dimeric Fc epsilon RI receptors for IgE on rat basophilic leukemia (RBL) basophilic leukemia (RBL) cells using time-resolved phosphorescence anisotropy. Receptors were studied both on living RBL cells and on membrane vesicles derived from RBL cell plasma membrane. The un cross-linked IgE-receptor complexes on cells and vesicles exhibit rotational correlation times that are consistent with those expected for freely rotating monomers, but a small fraction of these complexes on cells may be rotationally immobile. A comparison of the initial phosphorescence anisotropy values for erythrosin-labeled IgE-receptor complexes on cells and vesicles reveals a fast component of rotational motion that is greater on the vesicles and may be due to a site of segmental flexibility in the receptor itself. Dimers of IgE-receptor complexes formed with anti-IgE monoclonal antibodies appear to be largely immobile on cells, but they are mobile on vesicles with a 2-fold larger rotational correlation time than the monomeric complexes. The results suggest that dimeric IgE-receptor complexes undergo interactions with other membrane components on intact cells that do not occur on the membrane vesicles. The possible significance of these interactions to receptor function is discussed. PMID- 1310044 TI - A novel approach for chemically deglycosylating O-linked glycoproteins. The deglycosylation of submaxillary and respiratory mucins. AB - A new approach for removing O-glycosidically linked carbohydrate side chains from glycoproteins is described. Periodate oxidation of the C3 and C4 carbons in peptide-linked N-acetylgalactosamine (GalNAc) residues generates a dialdehyde product which, under mild alkaline conditions, undergoes a beta-elimination which releases carbohydrate and leaves an intact peptide core. The pH and time dependence, and intermediates of the elimination, have been extensively followed by carbon-13 NMR spectroscopy and amino acid analysis using ovine submaxillary mucin (OSM) as the substrate. The deglycosylation of OSM is complete and provides apomucin in high yield with an amino acid composition identical to the starting material. Carboxymethylated OSM when deglycosylated by this method gives an apomucin with an apparent molecular weight of ca. 700 x 10(3). The molecular weight is the same as that calculated for the peptide core of the starting mucin, demonstrating the absence of peptide core cleavage. This contrasts with the use of trifluoromethanesulfonic acid (TFMSA), which generates apomucin products of lower molecular weights. Oligosaccharide side chains substituted at C3 of the peptide-linked GalNAc residue are resistant to the oxidation and elimination. Glycoproteins containing these more complex side chains can be deglycosylated by pretreatment with TFMSA under mild (0 degree C) conditions, which removes peripheral sugars (while leaving the peptide-linked GalNAc residue intact), followed by oxidation and beta-elimination. Studies on the deglycosylation of porcine submaxillary mucin and human tracheobronchial mucin indicate that this approach provides more efficient removal of carbohydrate and less peptide core degradation than a more vigorous (25 degrees C) treatment with TFMSA alone. 13C NMR spectroscopic studies and carbohydrate analysis of the deglycosylation intermediates of the human mucin indicate that certain sialic acid containing and N-acetylglucosamine-containing oligosaccharides have elevated resistance to TFMSA treatment at 0 degrees C. By the use of neuraminidase, repeated mild TFMSA treatments, and multiple oxidations and beta-eliminations, the human mucin can be nearly completely deglycosylated. It is expected that all mucins and most glycoproteins containing O-glycosidic linkages can be readily and nearly completely deglycosylated using this combined approach. PMID- 1310045 TI - Ca2+ dependence of the interactions between protein C, thrombin, and the elastase fragment of thrombomodulin. Analysis by ultracentrifugation. AB - The two-way and three-way interactions among active-site-blocked bovine thrombin, bovine protein C, and the elastase fragment of rabbit thrombomodulin (elTM) were examined by analytical ultracentrifugation at 23.3 degrees C in 100 mM NaCl, 50 mM Tris (pH 7.65), and 1 mM benzamidine, in the presence of 0 to 5 mM calcium chloride. Thrombin and elTM form a tight (Kd less than 10(-8) M) 1:1 complex in the absence of Ca2+ that weakens with the addition of Ca2+ (Kd approximately 4 microM in 5 mM Ca2+). Without Ca2+, thrombin and protein C form a 1:1 complex (Kd approximately 1 microM) and what appears to be a 1:2 thrombin-protein C complex. The Kd for the 1:1 complex weakens over 100-fold in 5 mM CaCl2. Protein C and elTM form a Ca(2+)-independent 1:1 complex (Kd approximately 80 microM). Nearly identical binding to thrombin and elTM is observed when active-site-blocked activated bovine protein C is substituted for protein C. Thrombin inhibited by diisopropyl fluorophosphate and thrombin inhibited by a tripeptide chloromethyl ketone exhibited identical behavior in binding experiments, suggesting that the accessibility of protein C to the substrate recognition cleft of these two forms of thrombin is nearly equal. Human protein C binds with lower affinity than bovine protein C. Ternary mixtures also were examined. Protein C, elTM, and thrombin form a 1:1:1 complex which dissociates with increasing [Ca2+]. In the absence of Ca2+, protein C binds to the elTM-thrombin complex with an apparent Kd approximately 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310046 TI - Reduction of the small subunit of Escherichia coli ribonucleotide reductase by hydrazines and hydroxylamines. AB - Each polypeptide chain of protein R2, the small subunit of ribonucleotide reductase from Escherichia coli, contains a stable tyrosyl radical and an antiferromagnetically coupled diferric center. Recent crystallographic studies [Nordlund, P., Eklund, H., & Sjoberg, B.-M. (1990) Nature 345, 593-598] have shown that both the radical and the diiron site are deeply buried inside the protein and thus strongly support the hypothesis of long-range electron-transfer processes within protein R2. This study shows that monosubstituted hydrazines and hydroxylamines are able to reduce the tyrosyl radical and the ferric ions, under anaerobic conditions. It allows characterization of the site from which those compounds transfer their electrons to the iron/radical center. The efficiency of any given reducing agent is not solely governed by its redox potential but also by its size, its charge, and its hydrophobicity. We suggest, as a possible alternative to the long-range electron-transfer hypothesis, that conformational flexibility of the polypeptide chain might exist in solution and allow small molecules to penetrate the protein and react with the iron/radical center. This study also shows that two reduction mechanisms are possible, depending on which center, the radical or the metal, is reduced first. Full reduction of protein R2 yields reduced R2, characterized by a normal tyrosine residue and a diferrous center. Both the radical and the diferric center are regenerated from reduced R2 by reaction with oxygen, while only the diferric center is formed by reaction with hydrogen peroxide. PMID- 1310047 TI - Formation and photolability of low-spin ferrous cytochrome c peroxidase at alkaline pH. AB - The ferrous form of native cytochrome c peroxidase (CCP) is known to undergo a reversible transition when titrated over the pH range of 7.00-9.70. This transition produces a conversion from a pentacoordinate high-spin to a hexacoordinate low-spin heme active site and is clearly apparent in the heme optical absorption spectra. Here, we report the characterization of this transition and its effect upon the local heme environment using various optical spectroscopies. The formation of hexacoordinate low-spin heme is interpreted to involve the binding of His-52 at the distal site after the perturbation of the extensive H-bonded network within and around the heme pocket of CCP(II) at alkaline pH. Interestingly, CD investigations of CCP(II) in the far-UV and Soret regions indicate the dissappearance of a single high-spin species and the existence of at least two low-spin species of CCP(II) as the pH is raised above 7.90. Furthermore, transient resonance Raman experiments demonstrate that the hexacoordinate low-spin species can be photolyzed within 10-ns laser pulses, producing a species similar to the low-pH (high-spin) form of CCP(II) at alkaline pH. However, the extent of photolysis is quite pH dependent, with a maximum photodissociation yield at pH = 8.50. PMID- 1310048 TI - Regulation of diacylglycerol levels in carbachol-stimulated pancreatic acinar cells: relationship to the breakdown of phosphatidylcholine and metabolism to phosphatidic acid. AB - Rat pancreatic acinar cells prelabeled with [14C]palmitic acid and then exposed to carbachol (CCh) exhibited a time-dependent increase in 1,2-[14C]diacylglycerol ([14C]DAG) levels, which was first detected at 2 min and then continued to rise in a linear manner. There was a concomitant increase in [14C]phosphatidic acid, which plateaued after 2 min and then remained at steady-state levels. CCh also promoted the release of phosphocholine, but not choline, within 60 s and caused a decrease in [14C]phosphatidylcholine in cells prelabeled with [14C]glycerol after 15 min. The inability to detect a rise in [14C]phosphatidylethanol accumulation and a fall in [14C]phosphatidate levels in [14C]palmitate prelabeled cells after exposure to CCh plus ethanol documented the absence of a phospholipase D-mediated pathway. The rapid phosphorylation of diglyceride in homogenates from unstimulated and carbachol-treated cells increased with increasing concentrations of exogenous substrate, thereby affirming that carbachol stimulates the phosphorylation of DAG by promoting the accumulation of the diglyceride. These collective findings provide evidence for the existence of an integrative control mechanism for regulating endogenous DAG levels during pancreatic acinar cell activation involving phosphatidylcholine-specific phospholipase C and DAG kinase. PMID- 1310049 TI - Role of the lysine and arginine residues of vitellogenin in high affinity binding to vitellogenin receptors in locust oocyte membranes. AB - A specific cell surface receptor mediates the endocytosis of the yolk protein vitellogenin (VTG), a lipoglycoprotein, into growing oocytes of the insect Locusta migratoria. The ability of the VTG receptor to recognize VTG was analyzed in binding tests after modification by five lysine-specific and two other reagents. Progressive chemical modification of the lysyl and arginyl residues resulted in reduction or loss of the derivatized VTG to compete for binding to the VTG receptor with unmodified VTG. Although the precise role of the lysine residues in receptor binding remains to be defined we conclude that they are involved in expression of a recognition site interacting with the binding domain of the VTG receptor. Sulfhydryl groups are not involved in the conformation of the recognition site or binding ability of VTG. PMID- 1310050 TI - Synergistic effects of 12-O-tetradecanoylphorbol-13-acetate and dexamethasone on de novo synthesis of histidine decarboxylase in mouse mastocytoma P-815 cells. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) markedly enhanced the increase in L histidine decarboxylase (HDC) activity induced by dexamethasone in mouse mastocytoma P-815 cells, even with a concentration of the latter that had the maximal effect, whereas it induced a rapid and transient increase in HDC activity, which peaked after 3 h in the absence of dexamethasone. The synergistic effect of TPA on HDC activity induced by dexamethasone was detected after 4 h, a plateau level being reached by 6 h, which was similar to the time course with dexamethasone alone. TPA enhanced the induction of HDC activity by various glucocorticoids, but had no effect on the induction by dibutyryl cAMP, prostaglandin E2 or sodium butyrate. Both 1-oleoyl-2-acetylglycerol, a protein kinase C activator, and okadaic acid, a protein phosphatase inhibitor, enhanced the increase in HDC activity induced by dexamethasone, but 4 alpha-phorbol-12,13 didecanoate, an inactive derivative of TPA, did not. Protein kinase C inhibitors, such as staurosporin, H-7 and K255a, suppressed the increase in HDC activity induced by TPA with or without dexamethasone. The enhancement of HDC activity by dexamethasone was completely suppressed by cycloheximide or actinomycin D. Furthermore, TPA markedly enhanced the accumulation of HDC mRNA due to dexamethasone (5 to 10-fold, from 6 to 12 h after). TPA did not cause a significant increase in the level of either [3H]dexamethasone binding capacity or preformed HDC activity in cells. These results taken together suggest that dexamethasone-induced de novo synthesis of HDC in mastocytoma P-815 cells is up regulated by TPA-activated protein kinase C through the mechanism involving an increased rate of transcription. PMID- 1310052 TI - Evidence for insulin dependent hepatic microsomal gamma-linolenic acid chain elongation in spontaneously diabetic Wistar BB rats. AB - We studied hepatic microsomal gamma-linolenoyl-CoA elongation and fatty acid composition of liver microsomes in spontaneously diabetic Wistar BB rats. The liver microsomal gamma-linolenoyl-CoA elongation was decreased in diabetic Wistar BB rats during both normo- and hyperglycemic periods and restored during the hypoglycemic period following insulin treatment. These results are in agreement with our previously reported data on linoleic acid delta 6 and delta 5 desaturations and support the non-parallel relationship between the chain elongation system and the glycemia. The fatty acid composition of BB rat liver microsomes was only partially consistent with the gamma-linolenoyl-CoA elongation activity at the different periods of glycemia, probably because factors other than elongation impairments were involved in the evolution of fatty acid composition. PMID- 1310051 TI - Synergistic effects of cyclic AMP and Ca2+ ionophore A23187 on de novo synthesis of histidine decarboxylase in mastocytoma P-815 cells. AB - In the preceding paper (Kawai, H. et al. (1992) Biochim. Biophys. Acta 1133, 172 178), we reported that in mastocytoma P-815 cells dexamethasone and 12-O tetradecanoylphorbol-13-acetate (TPA) synergistically enhanced the de novo synthesis of L-histidine decarboxylase (HDC). Here we found that Ca2+ acted synergistically with cAMP in the induction of HDC mRNA and HDC activity in mastocytoma P-815 cells, and that the mechanism underlying the enzyme induction by Ca2+ plus cAMP was distinguishable from that by dexamethasone plus TPA. Ca2+ ionophore A23187, itself having no significant activity, markedly enhanced the induction of HDC activity by N6,O2'-dibutyryl cAMP (db cAMP) or cAMP-inducible prostaglandins such as PGE1, PGE2 and PGI2 in the presence of the phosphodiesterase inhibitor, Ro201724. However, A23187 had little effect on increases in HDC activity induced by other known stimulants, such as TPA, dexamethasone and sodium butyrate. These results suggest that A23187 has a specific effect on the induction of HDC activity due to an increased level of cAMP. The finding that both A23187 and cAMP enhanced HDC activity suggests that both Ca2+/calmodulin and cyclic nucleotide dependent protein kinase play essential roles in the process of enhancement of HDC activity. To examine this possibility, we studied the effects of W-7, an inhibitor of calmodulin, removal of extracellular Ca2+, and H-8, an inhibitor of cAMP-dependent protein kinase, on the enhancing activity of A23187 plus db cAMP. The enhancement of HDC activity by A23187 plus db cAMP was inhibited by W-7, removal of extracellular Ca2+, and H-8. The increase in HDC activity was due to the de novo synthesis of the enzyme, since it was suppressed by the addition of cycloheximide or actinomycin D, and was well correlated with the marked accumulation of a 2.7 kilobase HDC mRNA. Furthermore, the mechanism underlying the induction of HDC by db cAMP plus A23187 is distinguishable from that in the case of dexamethasone plus TPA, since preexposure to dexamethasone plus TPA for 12 h, for a plateau level to be reached, did not affect the subsequent increase in HDC activity due to db cAMP plus A23187. PMID- 1310053 TI - Characterization of EGTA-washed synaptosomal membrane with emphasis on its calmodulin-binding proteins. Demonstration of possible reconstitution with added calcium/calmodulin. AB - Endogenous calmodulin (CaM) in the EGTA-washed cerebral-cortical synaptosomal membrane (SM) preparation was estimated below 3 micrograms/ml protein by the semiquantitative immunoblot analysis (Natsukari, N., Ohta, H. and Fujita, M. (1989) J. Immunol. Methods 125, 159-166). Membrane-bound CaM was immunoelectron microscopically demonstrated in EGTA-washed, non-treated (control), and Ca(2+) treated cerebral-cortical synaptosomal membranes (SM) as well as for the SM enriched with added CaM. The density of CaM increased in the above order. CaM dependent adenylate cyclase and CaM-dependent protein kinase II (CaM-kinase II) activities were restored, whereas the phosphodiesterase (PDE) activity was not affected by exogenous CaM over all the Ca2+ concentrations tested. Adenylate cyclase at pCa 6.2 was synergistically activated either by GTP and CaM or by CaM and beta-adrenergic agonist, (+/-)-isoproterenol, reflecting the intactness of signal transduction pathway in the SM. Also demonstrated were the presence of protein kinase A, CaM-kinase II, and their endogenous substrates in the SM. Based on 32P-autoradiography and 125I-CaM overlay data certain CaM-binding proteins such as CaM-kinase II and synapsin I were identified on SDS-PAGE. Ca(2+) dependent and -independent CaMBPs were distinguished by 125I-CaM gel overlay with and without Ca2+. The former had bigger molecular size (greater than or equal to 49 kDa) than the latter (less than or equal to 34 kDa). Yield of Ca(2+)-dependent CaMBPs was not affected by Ca2+ concentration during preparation of the SM while that of Ca(2+)-independent CaMBPs was reduced by exposure to 100 microM Ca2+. In contrast with the CaMBPs of brain SM, those of enterocyte and eyrthrocyte plasma membranes especially, microvillous membrane of the enterocyte, showed quite distinct CaMBP profiles. The present findings suggested that the EGTA-washed SM preparation made a useful system for studying the role of CaM in the brain SM. PMID- 1310054 TI - The effect of a cAMP analogue on Ca2+ ionophore-, antigen- and agonist-induced inositol phosphate release in rat basophilic leukaemia (RBL-1) cells. AB - The effect of the stable cAMP analogue 8-Br-cAMP on leukotriene D4 (LTD4)-, 5'-N ethyl-carboxamidoadenosine (NECA)-, antigen- and Ca2+ ionophore-induced inositol phosphate (IP) production was studied in RBL-1 cells. The cAMP analogue significantly inhibited LTD4- and antigen induced-IP production, thus supporting the hypothesis of a negative interaction between cAMP and phosphoinositide breakdown in blood cells. Ionophore-induced IP release, which was blocked by a 5 lipoxygenase inhibitor and by a LT-receptor antagonist, and therefore is probably mediated by LTs, was also inhibited by 8-Br-cAMP. NECA-induced IP release was not significantly inhibited by the cyclic nucleotide, thus showing that the effect described herein is not a general action on receptor-activated phospholipase C. 8 Br-cAMP did, however, inhibit GTP gamma S-induced IP release in permeabilised RBL 1 cells, thus suggesting that the inhibition does not occur at the receptor level but might be due, at least in part, to an effect on some receptor-coupled G proteins. PMID- 1310055 TI - Lipoxin generation by human megakaryocyte-induced 12-lipoxygenase. AB - Eicosanoid biosynthesis was examined with a human megakaryocytic cell line (Dami). Megakaryocytes incubated with [1-14C]arachidonic acid and either ionophore A23187 or thrombin generated both thromboxane and 12 hydroxyheptadecatrienoic acid (HHTrE). Exposure to phorbol myristate acetate (PMA) for 1 through 9 days induced differentiation and revealed an increase in the conversion of [1-14C]arachidonate to cyclooxygenase- and lipoxygenase (LO) derived products. The LO-derived product was identified as 12S-HETE by its physical characteristics including GC/MS and chiral column SP-HPLC. PMA-treated Dami cells did not generate 5-HETE, leukotrienes or lipoxins from exogenous arachidonic acid while they did convert leukotriene A4 (LTA4) to lipoxin A4, lipoxin B4 and their respective all-trans isomers. In addition, COS-M6 cells transfected with a human 12-lipoxygenase cDNA and incubated with either arachidonic acid or LTA4 generated 12-HETE and lipoxins, respectively. The lipoxin profile generated by transfected COS-M6 cells incubated with LTA4 was similar to that generated by the PMA-treated Dami cells. Results indicate that human megakaryocytes can transform arachidonate and LTA4 to bioactive eicosanoids and that the 12-lipoxygenase appears upon further differentiation of these cells. In addition, they indicate that the 12-LO of human megakaryocytes and the 12-LO expressed by transfected COS cells can generate both lipoxins A4 and B4. Together they suggest that the human 12-LO can serve as a model of LX-synthetase activity with LTA4. PMID- 1310056 TI - Utility of immobilon-bound phosphoproteins as substrates for protein phosphatases from neutrophils. AB - Immobilon-bound phosphoproteins labeled with 32P were utilized as substrates to study the enzymes in neutrophils that are active against the major products of protein kinase C. The labeled proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred electrophoretically to immobilon-P membranes. Both particulate and soluble phosphatases were found to be active against the blotted phosphoproteins. Reactions were followed by autoradiography as the loss of 32P from individual protein bands. The tumor promoter okadaic acid and the hepatoxin microcystin-LR inhibited these reactions in a manner consistent with the enzymes being type 1 and/or 2A protein phosphatases. PMID- 1310057 TI - Transformation and inheritance of a hygromycin phosphotransferase gene in maize plants. AB - Embryogenic maize (Zea mays L.) callus cultures were transformed by microprojectile bombardment with a chimeric hygromycin phosphotransferase (HPT) gene and three transformed lines were obtained by selecting for hygromycin resistance. All lines contained one or a few copies of the intact HPT coding sequence. Fertile, transgenic plants were regenerated and the transmission of the chimeric gene was demonstrated through two complete generations. One line inherited the gene in the manner expected for a single, dominant locus, whereas two did not. PMID- 1310058 TI - Microprojectile bombardment of plant tissues increases transformation frequency by Agrobacterium tumefaciens. AB - Bombardment of plant tissues with microprojectiles in an effective method of wounding to promote Agrobacterium-mediated transformation. Tobacco cv. Xanthi leaves and sunflower apical meristems were wounded by microprojectile bombardment prior to application of Agrobacterium tumefaciens strains containing genes within the T-DNA encoding GUS or NPTII. Stable kanamycin-resistant tobacco transformants were obtained using an NPTII construct from particle/plasmid, particle wounded/Agrobacterium-treated or scalpel-wounded/Agrobacterium-treated potato leaves. Those leaves bombarded with particles suspended in TE buffer prior to Agrobacterium treatment produced at least 100 times more kanamycin-resistant colonies than leaves treated by the standard particle gun transformation protocol. In addition, large sectors of GUS expression, indicative of meristem cell transformation, were observed in plants recovered from sunflower apical explants only when the meristems were wounded first by particle bombardment prior to Agrobacterium treatment. Similar results in two different tissue types suggest that (1) particles may be used as a wounding mechanism to enhance Agrobacterium transformation frequencies, and (2) Agrobacterium mediation of stable transformation is more efficient than the analogous particle/plasmid protocol. PMID- 1310059 TI - Exchange of gene activity in transgenic plants catalyzed by the Cre-lox site specific recombination system. AB - The Cre-lox site-specific recombination system of bacteriophage P1 was used to excise a firefly luciferase (luc) gene which had previously been incorporated into the tobacco genome. The excision event was due to site-specific DNA recombination between two lox sequences flanking the luc gene and was catalyzed by the Cre recombinase introduced by cross-fertilization. Recombination resulted in the fusion of a promoter with a distally located hygromycin phosphotransferase (hpt) coding sequence and the excision event was monitored as a phenotypic change from expression of luc to expression of hpt. The efficiency of recombination was estimated from the exchange of gene activity and confirmed by molecular analysis. The relevance to potential applications of site-specific deletion-fusion events for chromosome engineering are discussed. PMID- 1310060 TI - The t(15;17) breakpoint in acute promyelocytic leukemia cluster within two different sites of the myl gene: targets for the detection of minimal residual disease by the polymerase chain reaction. AB - The retinoic acid receptor alpha (RAR alpha) and the myl gene are involved in the translocation breakpoint t(15;17)(q22;q21) in acute promyelocytic leukemia (APL). The majority of the breakpoint sites have been mapped within the second intron of the RAR alpha gene; however, the breakpoint sites on the myl gene are variable. Using primer sets derived from exon 2 or exon 3 of the RAR alpha gene and a primer derived from the myl cDNA, we were able to amplify the breakpoint sites of the fusion transcripts of all six APL RNA samples by the reverse transcriptase polymerase chain reaction (RT-PCR). A DNA fragment of 290 bp (breakpoint A) was amplified using RNA samples from three patients, whereas two DNA fragments of 630 and 774 bp (breakpoint B) were amplified using RNA samples from the other three APL patients. DNA sequence analysis of the amplified fragments suggests that the APL breakpoints clustered within two different introns of the myl gene. Northern blot analysis demonstrated that fusion transcripts RAR alpha/myl and myl/RAR alpha of varying sizes were detected in patients with different breakpoint sites on the myl gene. In addition, we analyzed five APL samples in complete remission and detected t(15;17)-positive cells. We conclude that the t(15;17) breakpoints in APL can be amplified by PCR using a single primer set and that minimal residual disease can be demonstrated in APL using RT-PCR. PMID- 1310062 TI - Activation of the AP-1 transcription factor by arabinofuranosylcytosine in myeloid leukemia cells. AB - Previous studies have shown that 1-beta-D-arabinofuranosylcytosine (ara-C) induces transcription of the c-jun immediate early response gene in human myeloid leukemia cells. The present work has examined the mechanisms responsible for this effect. Deleted forms of the c-jun promoter were linked to the chloramphenicol acetyltransferase (CAT) gene and transfected into KG-1 cells. The results demonstrate that ara-C-induced c-jun transcription is mediated by an element between positions -74 and -20 upstream to the start site. Electrophoretic mobility shift assays with the fragment f(-74/-20) showed an increase in binding with nuclear proteins from ara-C-treated cells as compared with untreated cells. Competition with an oligonucleotide containing the AP-1 consensus sequence indicated that ara-C stimulates binding of nuclear proteins at the AP-1 site in the c-jun promoter. These findings were confirmed in other gel shift studies with the collagenase enhancer AP-1 consensus sequence and with a DNA fragment containing an altered AP-1 site. The binding of JUN/AP-1 was maximal at 1 hour of ara-C treatment and decreased to baseline levels at 12 hours. The finding that ara-C induces AP-1 binding in the absence of protein synthesis indicated that this agent activates already synthesized JUN/AP-1. To confirm these findings, the AP-1 consensus sequence was introduced 5' to the heterologous SV40 promoter. The results show that AP-1 enhances SV40 promoter activity in ara-C-treated cells. Taken together, these findings indicate that: (1) enhancement of JUN/AP-1 activity in ara-C-treated cells involves a posttranslational modification of JUN/AP-1; and (2) binding of activated JUN/AP-1 to the AP-1 site in the c-jun promoter confers ara-C inducibility of this gene. PMID- 1310061 TI - Insight into the nature and site of oxygen-centered free radical generation by endothelial cell monolayers using a novel spin trapping technique. AB - Spin trapping, a sensitive and specific means of detecting free radicals, is optimally performed on cell suspensions. This makes it unsuitable for the study of adherent endothelial cell monolayers because disrupting the monolayer to induce a cell suspension could introduce confounding factors. This problem was eliminated through the use of endothelial cells that were grown to confluence on microcarrier beads. Using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), the nature of free radical species generated by suspensions of microcarrier bead adherent porcine pulmonary endothelial cells under various forms of oxidant stress was examined. Exposure of these endothelial cells to paraquat resulted in the spin trapping of superoxide (.O2-). Endothelial cell incubation in the presence of either bolus or continuous fluxes of hydrogen peroxide (H2O2) yielded spin trap evidence of hydroxyl radical formation, which was preventable by pretreating the cells with deferoxamine. Chromium oxalate which eliminates extracellular electron paramagnetic resonance spectrometry (EPR) signals, prevented the detection of DMPO spin adducts generated by paraquat but not H2O2 treated endothelial cells. When endothelial cells were coincubated with PMA stimulated monocytes evidence of both .O2- and hydroxyl radical production was detected, whereas with PMA-stimulated neutrophils only .O2- production could be confirmed. Neutrophil elastase, cathepsin G, and the combination of PMA and A23187 have previously been suggested to induce endothelial cell oxy-radical generation. However, exposure of endothelial cells to each of these agents did not yield DMPO spin adducts or cyanide-insensitive endothelial cell O2 consumption. These data indicate that endothelial cell exposure: to paraquat induces extracellular .O2- formation; to H2O2 leads to intracellular hydroxyl radical production; and to elastase, cathepsin G, or A23187/PMA does not appear to cause oxy-radical generation. PMID- 1310063 TI - Effect of activin A on globin gene expression in purified human erythroid progenitors. AB - The regulatory control of human erythropoiesis through a purified protein, activin A, was examined. Previous studies using mixed populations of bone marrow cells suggested that activin A has an indirect effect on cellular proliferation and DNA synthesis of erythroid progenitors through the mediation of accessory cells. In present studies, the cultures of purified erythroid progenitors were used to examine the effect of activin A on globin gene expression. Human erythroid burst-forming units (BFU-E) were partially purified from peripheral blood, and after 8 days of culture the cells generated consisted mainly of erythroid colony-forming units (CFU-E). It was found that the subsequent 7-day cultures of these purified progenitors yielded similar numbers and size distributions of erythroid colonies, regardless of the presence of activin A in the cultures. In addition, these erythroid progenitor cells were responsive, in terms of stimulation of DNA synthesis, to the addition of erythropoietin, but not to treatment by activin A. Therefore, once the erythroid progenitors are depleted of accessory cells, activin A has little effect on both the proliferation and the DNA synthesis of these progenitors. However, when these purified erythroid progenitors were cultured in the presence of activin A, the levels of all alpha, beta, and epsilon globin transcripts and hemoglobins were significantly increased. In addition, disuccinimidyl suberate was found to chemically cross link 125I-activin A to cell surface binding proteins (45 to 54 Kd) in both purified erythroid progenitors and K562 cells. The labeling of these binding proteins was specifically inhibited by the presence of unlabeled activin A, but not transforming growth factor-beta. These results suggest that, in addition to its indirect effect on DNA synthesis and cellular proliferation of erythroid progenitors, activin A directly affects the levels of globin mRNAs and hemoglobins in developing human erythroid cells through its specific surface binding receptor(s). PMID- 1310064 TI - Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma. AB - Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by-product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy. PMID- 1310065 TI - Increase in plasma thrombomodulin in lupus erythematosus with antiphospholipid antibodies. PMID- 1310066 TI - Overexpression of human topoisomerase I in baby hamster kidney cells: hypersensitivity of clonal isolates to camptothecin. AB - The 3645-base pair human topoisomerase I complementary DNA (cDNA) clone isolated by D'Arpa et al. (Proc. Natl. Acad. Sci. USA, 85:2543-2547, 1988) and a mutated version of the cDNA encoding a protein with phenylalanine instead of tyrosine at position 723 have been overexpressed 2- to 5-fold in stably transfected baby hamster kidney cells. The overexpressed proteins are the same size as the topoisomerase I present in Hela cells, indicating that the cDNA clone contains the complete topoisomerase I coding sequence. Some human colon carcinoma cells have increased levels of topoisomerase I and are hypersensitive to the drug camptothecin. The overexpressed wild-type topoisomerase I does not affect the cell growth or morphology of the baby hamster kidney cells, suggesting that elevated levels of topoisomerase I alone are not sufficient to cause cell transformation. However, the overexpressed wild-type protein is active, as shown by the hypersensitivity of clonal cell lines to camptothecin. The mutant form of topoisomerase I is enzymatically inactive by two criteria. First, extracts of Escherichia coli cells carrying the mutant cDNA contain no activity capable of relaxing superhelical DNA under conditions where activity is easily detectable in extracts from cells containing the wild-type cDNA. Second, baby hamster kidney cells stably transfected by the mutant cDNA are no more sensitive to camptothecin than control untransfected cells. These results indicate that tyrosine 723 is essential for enzyme activity and are consistent with predictions based on homology comparisons with the yeast enzymes, that this is the active-site tyrosine in the human topoisomerase I. PMID- 1310067 TI - Novel compounds inhibit estrogen formation and action. AB - Estrogens are well known to play a predominant role in human breast cancer. The current endocrine therapy of breast cancer consists in administering an antiestrogen which blocks the action of estrogens at the receptor level. However, the currently available antiestrogens possess mixed estrogenic and antiestrogenic activity, thus limiting their potential therapeutic efficacy. The present data show that a series of new estrogen derivatives demonstrate not only pure antiestrogenic activity in the sensitive in vivo mouse uterus assay, but simultaneously exert potent inhibitory effects on 17 beta-hydroxysteroid dehydrogenase activity, the enzyme responsible for the formation of 17 beta estradiol from estrone, the last step in estrogen formation. Such compounds having a dual site of inhibitory action, namely on estrogen formation and on the estrogen receptor, could well lead to an improved endocrine therapy of breast and other estrogen-sensitive cancers as well as other nonmalignant estrogen-sensitive diseases. PMID- 1310068 TI - Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. AB - The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element. PMID- 1310069 TI - Neoplastic progression by EJ/ras at different steps of transformation in vitro of human uroepithelial cells. AB - The biological effects of expression of mutant ras at different stages of human uroepithelial cell (HUC) tumorigenesis were tested after transfection of EJ/ras into nonestablished HUC and three isogeneic cell lines representing different steps in HUC transformation in vitro. Transfection with EJ/ras failed to immortalize diploid HUC and also failed to cause tumorigenic conversion of a near diploid SV40-immortalized HUC line (SV-HUC) except at one of six nude mouse inoculation sites. In contrast, EJ/ras-transfected aneuploid low-grade squamous cell carcinoma cells formed undifferentiated, invasive carcinomas at four of six inoculation sites. Furthermore, EJ/ras accelerated tumor growth in MC-ppT11-HA2, an aneuploid high-grade transitional cell carcinoma line, as determined by decreased tumor latent periods and doubling times. These results suggest that EJ/ras contributes to progression, possibly by accelerating tumor growth, but does not in itself cause tumorigenic transformation of uroepithelial cells. To test whether chromosome losses accompanied EJ/ras transformation of SV-HUC, the karyotype of the one SV-HUC tumorigenic transformant obtained (above) was examined. This tumor cell line showed losses of chromosome arms 3p, 10p, 11p, and 18, all of which have been hypothesized to contain genes that suppress cancer development. Therefore, these results also provide new evidence suggesting that genetic losses may be required for mutant ras to contribute to HUC tumorigenic progression. PMID- 1310070 TI - p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. AB - The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption. PMID- 1310072 TI - Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. AB - Initiation of translation on picornavirus RNAs is accomplished through internal binding of ribosomes to a complex cis-acting element. Here we show that efficient function of this element involves two appropriately spaced smaller elements: UUUCC and an AUG. This conclusion emerged from analysis of the genome structures of spontaneous revertants of mutant polioviruses with extended insertions between the UUUCC and AUG motifs. It was confirmed by the results obtained with specially designed constructs. A similarity to the prokaryotic translation initiation mechanism, which involves the Shine-Dalgarno sequence, is emphasized, but in the picornavirus system the position of the UUUCC must be strictly fixed relative to upstream cis-acting elements, and the AUG may not necessarily serve as an initiation codon. PMID- 1310071 TI - FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter. AB - The receptors for at least two hematopoietic growth factors, namely the stem cell factor and colony-stimulating factor 1, belong to class III receptor tyrosine kinases. Here we describe cloning of a partial complementary DNA for FLT4, an additional member of this gene family from human leukemia cells. The FLT4 tyrosine kinase domain is 79% homologous with the previously cloned FLT1 (M. Shibuya et al., Oncogene, 5: 519-524, 1990) tyrosine kinase and maps to the chromosomal region 5q33-qter. We have found FLT4 expression in human placenta, lung, heart, and kidney, whereas the pancreas and brain appeared to contain very little if any FLT4 RNA. The results suggest that FLT4 functions in multiple adult tissues. PMID- 1310074 TI - MAP kinase by any other name smells just as sweet. PMID- 1310073 TI - A cyclin A-protein kinase complex possesses sequence-specific DNA binding activity: p33cdk2 is a component of the E2F-cyclin A complex. AB - The E2F transcription factor has been found in association with the cyclin A protein, and this complex accumulates during the S phase of the cell cycle, suggesting that E2F may play a role in cell cycle control. In independent studies, cyclin A has been shown to be associated with two other proteins, the Rb related p107 protein and the cdc2-related p33 cdk2 protein kinase. Through an analysis of the E2F-cyclin A complex, we now find that both the p107 protein and the cdc2-related p33cdk2 kinase are components of the previously described complex. Moreover, the complex possesses H1 kinase activity. These results thus define a cyclin A-cdk2 kinase complex that possesses sequence-specific DNA binding activity. This suggests that the cdk2 kinase may phosphorylate other DNA bound substrates, and that one role of the E2F factor may be to localize this protein kinase to the DNA. PMID- 1310076 TI - Skin kinetics of azole antifungal drugs. PMID- 1310075 TI - Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors. AB - We have cloned ActR-IIB, which encodes four new activin receptor isoforms belonging to the protein serine/threonine kinase receptor family. Two of the ActR IIB isoforms have higher affinity for activin A than the previously cloned activin receptor and differ from each other by the inclusion of an alternatively spliced segment in the cytoplasmic juxtamembrane region. A second alternative splicing event generates two additional receptor isoforms that lack a proline cluster in the external juxtamembrane region and have lower affinity for activin A. All isoforms bind inhibin A with low affinity. Thus, the repertoire of activin receptors includes species that differ in ligand binding affinity, cytoplasmic domain structure, or both. This receptor heterogeneity might underlie the sharply different responses that activin can elicit in a dose- or cell-specific manner. PMID- 1310077 TI - Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease. AB - Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended. PMID- 1310078 TI - Drug overdose: salicylates. PMID- 1310079 TI - Ileal pouch-anal anastomosis. PMID- 1310080 TI - Antimutagenicity of a low molecular weight superoxide dismutase mimic against oxidative mutagens. AB - A set of stable nitroxide free radicals that are used as spin labels have been shown to possess metal-independent superoxide dismutase-like activity. Unlike superoxide dismutase (SOD), these compounds are low molecular weight, and readily penetrate into the cell. A representative nitroxide, 4-hydroxy-2,2,6,6 tetramethylpiperidinyloxy (Tempol), was investigated for antimutagenic activity in the XPRT forward mutation assay in CHO AS52 cells. AS52 cells were exposed to hydrogen peroxide, or the hypoxanthine/xanthine oxidase superoxide generating system, in the presence or absence of 10 mM Tempol. Tempol itself was not mutagenic or toxic to AS52 cells. Tempol protected cells nearly completely from the cytotoxic and mutagenic effects of hydrogen peroxide and hypoxanthine/xanthine oxidase. We have previously shown that nitroxides do not alter the extracellular concentration of hydrogen peroxide, and that they are taken up by mammalian cells, suggesting that the antimutagenic activity of Tempol is an intracellular phenomenon. PMID- 1310081 TI - Hepatocyte membrane stabilization by prostaglandins E1 and E2: favorable effects on rat liver injury. AB - When prostaglandin (PG) E1 was continuously administered to rats from 24 hours before giving a dose of carbon tetrachloride, deranged serum glutamic pyruvic transaminase levels and prothrombin time were significantly reduced 12 hours after intoxication compared with controls. A similar effect of PGE1 was seen at 24 hours in D-galactosamine-intoxicated rats. Liver histology showed a comparable attenuation of injury in these rats. These results were consistent with reported effects of PGE2, suggesting that both prostaglandins may share a common pathway in protection against liver injury. When PGE1 or 16,16'-dimethyl PGE2 was added to the medium of primary cultured rat hepatocytes, lipid peroxidation-dependent killing of the cells by tert-butyl hydroperoxide was significantly attenuated without affecting the extent of malondialdehyde accumulation compared with controls. Both prostaglandins significantly reduced the extent of increased plasma membrane microviscosity of these cells assessed by 1-[4-(trimethyl ammonio)phenyl]-6-phenyl-1,3,5-hexatriene. PGE1 and PGE2 may possess cytoprotective effects on liver parenchymal cells through stabilization of membrane microviscosity, which may contribute to protection against liver injury. PMID- 1310082 TI - Squamous papilloma of the esophagus associated with the human papillomavirus. AB - Squamous cell papilloma of the esophagus is a rare lesion involving less than 60 case reports worldwide. These lesions are generally asymptomatic but may at times grow and spread rapidly. One fatality, a result of massive dissemination, has been reported. Until recently, human papillomavirus had not been identified in association with esophageal papillomas. A second case, to the authors' knowledge, of esophageal papillomas associated with human papillomavirus is reported. The virus has been previously shown to be associated with abnormal squamous epithelium in and adjacent to esophageal carcinoma. The virus was identified from biopsy specimens obtained at endoscopy using DNA in situ hybridization techniques. The strain of human papillomavirus identified is similar to those found in the oropharynx and genital tract, raising the possibility of sexual transmission. This case also differs from the previous case report involving the human papillomavirus because of the patient's benign clinical course. Our case serves to highlight differences that are perhaps unique to the human papillomavirus. Multiple papillomas found in a proximal location within the esophagus seem to favor involvement of the human papillomavirus. Isolated lesions located distally appear more characteristic of chronic gastroesophageal reflux as an etiology. The syndrome of squamous cell papillomas involving the esophagus is reviewed in the article. PMID- 1310083 TI - Familial visceral neuropathy with neuronal intranuclear inclusions: diagnosis by rectal biopsy. AB - A family with a visceral neuropathy manifested as chronic idiopathic intestinal pseudo-obstruction is reported. Diagnoses were made histologically by simple rectal biopsy. Discrete eosinophilic intranuclear inclusions, diagnostic of a disease known as neuronal intranuclear inclusion disease, were found in the submucosal ganglion cells. Abnormalities of the autonomic nervous system were identified by pupillary examination and electroretinography. In this family, three of four siblings were affected by the disease, which is apparently transmitted from the paternal side. This pedigree was unique for several reasons: (a) diagnosis in multiple members of two generations indicates that this familial visceral neuropathy was expressed in an autosomal dominant manner, (b) central autonomic nervous system abnormalities were detected by eye examination, and (c) the definitive pathological diagnosis was established antemortem by rectal biopsy in all cases. PMID- 1310084 TI - Detection of hepatitis C virus RNA in chronic non-A, non-B liver disease. AB - Serum samples were tested for detection of hepatitis C virus (HCV) RNA from 156 patients with chronic non-A, non-B liver disease. HCV RNA was detected in 121 (93.8%) of 129 patients positive for anti-C100-3 but was also found in 15 (55.6%) of 27 patients negative for anti-C100-3. The rate of positivity for HCV RNA was not significantly different among various stages of liver diseases. These results showed that HCV continues to replicate even in advanced liver disease and that it seems to be related to half of the cases of chronic non-A, non-B liver disease negative for anti-C100-3. PMID- 1310085 TI - Gastric chief cells: receptors and signal-transduction mechanisms. AB - Elucidation of receptors and mediators regulating gastric pepsinogen secretion has lagged behind understanding of the factors that control acid secretion. During the past decade, as a consequence of the development of in vitro models for studying the control of pepsinogen secretion at the cellular level, much information about chief cell receptors and signal-transduction mechanisms has been obtained, including the identification and characterization of receptors for secretin, vasoactive intestinal polypeptide, cholinergic agonists, gastrin, cholecystokinin, peptide YY, and cholera toxin. Moreover, these cell preparations have permitted secretagogue-induced changes in chief-cell calcium concentration, protein kinase C distribution, and phosphoinositide and cyclic nucleotide content to be measured and related to changes in pepsinogen secretion. This article reviews these advances, discusses areas of uncertainty and controversy, and indicates areas for future investigation. PMID- 1310086 TI - Changes in state of the Wx-m5 allele of maize are due to intragenic transposition of Ds. AB - The molecular basis for the unusual phenotype conditioned by the waxy(Wx)-m5 Ds allele has been elucidated. Unlike most Ds alleles, Wx-m5 is phenotypically wild type in the absence of Ac. We find that the Wx-m5 gene contains a 2-kb Ds element at -470 relative to the start of Wx transcription, representing the most 5' insertion of any transposable element allele characterized to date in plants. Despite its wild type phenotype, Wx-m5 has reduced levels of Wx enzymatic activity indicating that Ds insertion influences Wx gene expression. In the presence of Ac, Wx-m5 kernels have sectors of null expression on a wild-type background and give rise to stable wx and unstable wx-m germinal derivatives. Seventeen of 20 derivatives examined are wx-m alleles and at least 15 of these appear to result from intragenic transposition of Ds from -470 to new sites within the Wx gene. Three wx-m alleles contain two Ds elements, one at -470 and a second in Wx coding sequences. Surprisingly, only 3 out of 20 derivatives are stable wx mutants and these have sustained gross rearrangements of Wx and flanking sequences. For most other maize transposable element alleles somatic sectors and germinal derivatives usually arise following element excision or deletions of element sequences. In contrast, element insertion following intragenic transposition is apparently responsible for most of the somatic sectors and germinal derivatives of Wx-m5. PMID- 1310087 TI - Phage lambda has an analog of Escherichia coli recO, recR and recF genes. AB - The RecF pathway catalyzes generalized recombination in Escherichia coli that is mutant for recBC, sbcB and sbcC. This pathway operating on conjugational recombination requires the recA, recF, recJ, recN, recO, recQ, recR, ruvA, ruvB and ruvC genes. In contrast, lambda mutant for its own recombination genes, int, red alpha and red beta, requires only the recA and recJ genes to recombine efficiently in recBC sbcB sbcC cells. Deletion of an open reading frame in the ninR region of lambda results in an additional requirement for recO, recR and recF in order to recombine in recBC sbcB sbcC mutant cells. This function, designated orf for recO-, recR- and recF-like function, is largely RecF pathway specific. PMID- 1310088 TI - Relationship of the cAMP-dependent protein kinase pathway to the SNF1 protein kinase and invertase expression in Saccharomyces cerevisiae. AB - The SNF1 protein kinase and the associated SNF4 protein are required for release of glucose repression in Saccharomyces cerevisiae. To identify functionally related proteins, we selected genes that in multicopy suppress the raffinose growth defect of snf4 mutants. Among the nine genes recovered were two genes from the cAMP-dependent protein kinase (cAPK) pathway, MSI1 and PDE2. Increased dosage of these genes partially compensates for defects in nutrient utilization and sporulation in snf1 and snf4 null mutants, but does not restore invertase expression. These results suggest that SNF1 and cAPK affect some of the same cellular responses to nutrients. To examine the role of the cAPK pathway in regulation of invertase, we assayed mutants in which the cAPK is not modulated by cAMP. Expression of invertase was regulated in response to glucose and was dependent on SNF1 function. Thus, a cAMP-responsive cAPK is dispensable for regulation of invertase. PMID- 1310089 TI - Catabolite gene activator protein activation of lac transcription. PMID- 1310090 TI - Positive and negative control of ompB transcription in Escherichia coli by cyclic AMP and the cyclic AMP receptor protein. AB - The ompB operon encodes OmpR and EnvZ, two proteins that are necessary for the expression and osmoregulation of the OmpF and OmpC porins in Escherichia coli. We have used in vitro and in vivo experiments to show that cyclic AMP and the cyclic AMP receptor protein (CRP) directly regulate ompB. ompB expression in an ompB lacZ chromosomal fusion strain was increased two- to fivefold when cells were grown in medium containing poor carbon sources or with added cyclic AMP. In vivo primer extension analysis indicated that this control is complex and involves both positive and negative effects by cyclic AMP-CRP on multiple ompB promoters. In vitro footprinting showed that cyclic AMP-CRP binds to a 34-bp site centered at -53 and at -75 in relation to the start sites of the major transcripts that are inhibited and activated, respectively, by this complex. Site-directed mutagenesis of the crp binding site provided evidence that this site is necessary for the in vivo regulation of ompB expression by cyclic AMP. Control of the ompB operon by cyclic AMP-CRP may account for the observed regulation of the formation of OmpF and OmpC by this complex (N. W. Scott and C. R. Harwood, FEMS Microbiol. Lett. 9:95-98, 1980). PMID- 1310091 TI - Influence of cyclic AMP, agmatine, and a novel protein encoded by a flanking gene on speB (agmatine ureohydrolase) in Escherichia coli. AB - The speB gene of Escherichia coli encodes agmatine ureohydrolase (AUH), a putrescine biosynthetic enzyme. The speB gene is transcribed either from its own promoter or as a polycistronic message from the promoter of the speA gene encoding arginine decarboxylase. Two open reading frames (ORF1 and ORF2) are present on the strand complementary to speB; approximately 90% of ORF2 overlaps the speB coding region. Analysis of transcriptional and translational fusions of ORF1 or ORF2 to lacZ revealed that ORF1 encoded a novel protein while ORF2 was not transcribed. Deletion of ORF1 from a plasmid containing ORF1, ORF2, and speB reduced the activity of AUH by 83%. In contrast, the presence of plasmid-encoded ORF1 caused an 86% increase in chromosomally encoded AUH activity. ORF1 did not stimulate alkaline phosphatase expressed from a phi(speB-phoA) transcriptional fusion encoded on the same plasmid. Western analysis (immunoblot) of a phi(ORF1 lacZ) translational fusion revealed that ORF1 encodes a 25.3-kDa protein. Agmatine induced transcription of phi(speB-phoA) but not phi(speA-phoA) fusions. Consequently, agmatine affects selection between the monocistronic and the polycistronic modes of speB transcription. In contrast, cyclic AMP (cAMP) repressed AUH activity of chromosomally encoded AUH but had no effect on plasmid borne speB nor phi(speB-phoA). It is concluded that ORF1 encodes a protein which is a posttranscriptional regulator of speB, agmatine induces speB independent of speA, and cAMP regulates speB indirectly. PMID- 1310092 TI - Propagation of pSC101 plasmids defective in binding of integration host factor. AB - Integration host factor (IHF), a multifunctional protein of E. coli, normally is required for the replication of plasmid pSC101. T. T. Stenzel, P. Patel, and D. Bastia (Cell 49:709-717, 1987) have reported that IHF binds to a DNA locus near the pSC101 replication origin and enhances a static bend present in this region; mutation of the IHF binding site affects the plasmid's ability to replicate. We report here studies indicating that the requirement for IHF binding near the pSC101 replication origin is circumvented partially or completely by (i) mutation of the plasmid-encoded repA (replicase) gene or the chromosomally encoded topA gene, (ii) the presence on the plasmid of the pSC101 partition (par) locus, or (iii) replacement of the par locus by a strong transcriptional promoter. With the exception of the repA mutation, the factors that substitute for a functional origin region IHF binding site are known to alter plasmid topology by increasing negative DNA supercoiling, as does IHF itself. These results are consistent with the proposal that IHF binding near the pSC101 replication origin promotes plasmid replication by inducing a conformational change leading to formation of a repA dependent DNA-protein complex. A variety of IHF-independent mechanisms can facilitate formation of the putative replication-initiation complex. PMID- 1310093 TI - Insertional inactivation of an Escherichia coli urease gene by IS3411. AB - Ureolytic Escherichia coli are unusual clinical isolates that are found at various extraintestinal sites of infection, predominantly the urinary tract. The urease-positive phenotype is unstable in approximately 25% of these isolates, and urease-negative segregants are produced at a high frequency. We have studied the nature of the urease-positive-to-negative transition in one of these isolates, designated E. coli 1021. Southern hybridization experiments with genomic DNA extracted from seven independent E. coli 1021 urease-negative segregants revealed the presence of a 1.3-kb DNA insertion in the urease gene cluster. A DNA fragment containing the DNA insertion was cloned from one of the urease-negative segregants. This cloned DNA fragment was capable of mediating cointegrate formation with the conjugative plasmid pOX38, suggesting that the DNA insertion was a transposable element. The insert was identified as an IS3411 element in ureG by DNA sequence analysis. A 3-bp target duplication (CTG) flanking the insertion element was found. DNA spanning the insertion site was amplified from the other six urease-negative segregants by using the polymerase chain reaction. The DNA sequence of the amplified fragments indicated that an IS3411 element was found in an identical site in all urease-negative segregants examined. These data suggest that in E. coli 1021, IS3411 transposes at a high frequency into ureG at a CTG site, disrupting this gene and eliminating urease activity. PMID- 1310094 TI - Molecular cloning and physical mapping of the otsBA genes, which encode the osmoregulatory trehalose pathway of Escherichia coli: evidence that transcription is activated by katF (AppR) AB - It has been shown previously that the otsA and otsB mutations block osmoregulatory trehalose synthesis in Escherichia coli. We report that the transcription of these osmoregulated ots genes is dependent on KatF (AppR), a putative sigma factor for certain stationary phase- and starvation-induced genes. The transcription of the osmoregulated bet and proU genes was not katF dependent. Our genetic analysis showed that katF carries an amber mutation in E. coli K-12 and many of its derivatives but that katF has reverted to an active form in the much-used strain MC4100. This amber mutation in katF leads to strain variations in trehalose synthesis and other katF-dependent functions of E. coli. We have performed a molecular cloning of the otsBA genes, and we present evidence that they constitute an operon encoding trehalose-6-phosphate phosphatase and trehalose-6-phosphate synthase. A cloning and restriction site analysis, performed by comparing the cloned fragments with the known physical map of the E. coli chromosome, revealed that the otsBA genes are situated on a 2.9-kb HindIII fragment located 8 to 11 kb clockwise of tar (41.6 min). PMID- 1310095 TI - Molecular characterization of the 28- and 31-kilodalton subunits of the Legionella pneumophila major outer membrane protein. AB - The major outer membrane protein of Legionella pneumophila exhibits an apparent molecular mass of 100 kDa. Previous studies revealed the oligomer to be composed of 28- and 31-kDa subunits; the latter subunit is covalently bound to peptidoglycan. These proteins exhibit cross-reactivity with polyclonal anti-31 kDa protein serum. In this study, we present evidence to confirm that the 31-kDa subunit is a 28-kDa subunit containing a bound fragment of peptidoglycan. Peptide maps of purified proteins were generated following cyanogen bromide cleavage or proteolysis with staphylococcal V8 protease. A comparison of the banding patterns resulting from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) revealed a common pattern. Selected peptide fragments were sequenced on a gas phase microsequencer, and the sequence was compared with the sequence obtained for the 28-kDa protein. While the amino terminus of the 31-kDa protein was blocked, peptide fragments generated by cyanogen bromide treatment exhibited a sequence identical to that of the amino terminus of the 28-kDa protein, but beginning at amino acid four (glycine), which is preceded by methionine at the third position. This sequence, (Gly-Thr-Met)-Gly-Pro-Val-Trp-Thr-Pro-Gly-Asn ... , confirms that these proteins have a common amino terminus. An oligonucleotide synthesized from the codons of the common N-terminal amino acid sequence was used to establish by Southern and Northern (RNA) blot analyses that a single gene coded for both proteins. With regard to the putative porin structure, we have identified two major bands at 70 kDa and at approximately 120 kDa by nonreducing SDS-PAGE. The former may represent the typical trimeric motif, while the latter may represent either a double trimer or an aggregate. Analysis of these two forms by two-dimensional SDS-PAGE (first dimensions, nonreducing; second dimensions, reducing) established that both were composed of 31- and 28-kDa subunits cross linked via interchain disulfide bonds. These studies confirm that the novel L. pneumophila major outer protein is covalently bound to peptidoglycan via a modified 28-kDa subunit (31-kDa anchor protein) and cross-linked to other 28-kDa subunits via interchain disulfide bonds. PMID- 1310096 TI - The effect of 3 mouthrinses on plaque and gingivitis development. AB - The aim of this study was to evaluate the effect of 3 mouthrinses, Listerine Antiseptic (thymol), Peridex (chlorhexidine), Perimed (povidone iodine and hydrogen peroxide), and a placebo (water) on the development of dental plaque and gingivitis, when used as the only oral hygiene procedure for 14 days. 71 subjects were entered into a randomized, double-blind study. At the baseline examination, papillary bleeding score (PBS), and plaque index (PI) were registered, after which subjects received supragingival prophylaxis and were assigned to 1 of 4 study cells. Subjects were asked to refrain from all oral hygiene procedures except for the supervised 14-day 2 x daily rinsing with the assigned preparation. At day 14, the same clinical parameters were again registered. Statistical analysis was performed by a one-way analysis of variance (ANOVA) to compare the 4 groups, followed by Duncan's multiple range test to determine specific group differences. At baseline, average PBS and PI scores were similar for all 4 groups. After 14 days, the average PBS for Peridex and Perimed was significantly lower than for Listerine Antiseptic and water. The frequency of interdental units with a PBS greater than 2 was significantly lower for Peridex and Perimed than for Listerine Antiseptic and water. We concluded that both Peridex and Perimed were effective in reducing plaque and gingivitis when used as a 2 x daily mouthrinse by subjects refraining from other oral hygiene procedures. In vitro, a synergistic effect was assumed when inhibition was achieved with Perimed at the same or greater dilution than was achieved with povidone-iodine alone. PMID- 1310097 TI - Cutaneous angiocentric T-cell lymphoma associated with Epstein-Barr virus. AB - BACKGROUND: Two unusual cases of cutaneous angiocentric T-cell lymphoma were found to be associated with Epstein-Barr virus infection. OBJECTIVE: The objective was to study the clinical course and the response of the disease to conventional chemotherapy. METHODS: Histologic specimens from both patients were studied. Clonal proliferation was assessed by Southern blot hybridization. RESULTS: The disease in both patients was rapidly progressive and responded poorly to aggressive treatment. Biopsy specimens showed infiltration of atypical lymphoid cells with angiocentricity and angiodestruction, which probably resulted in the observed tissue necrosis. Clonal proliferation of Epstein-Barr virus DNA was detected in tissue from primary skin lesions and disseminated nasal lesions. CONCLUSION: Epstein-Barr virus-associated angiocentric T-cell lymphoma in our patients was characterized by an aggressive course and resistance to conventional chemotherapy. A search for Epstein-Barr virus and the human T-lymphotropic virus should be performed in patients with atypical features of cutaneous T-cell lymphoma. PMID- 1310098 TI - Autoantibodies to leucocyte antigens in hydralazine-associated nephritis. AB - Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production. PMID- 1310099 TI - High frequency of myelomonocytic tumors in aging E mu L-myc transgenic mice. AB - Transgenic mice that contain constructs of the L-myc gene under the transcriptional control of the immunoglobulin heavy chain enhancer (E mu) develop thymic hyperplasia and are predisposed to T cell lymphomas. Here we describe a second form of malignancy that occurs in aging E mu L-myc transgenic mice. The mean latency period for the development of this malignancy is longer compared with the E mu L-myc T cell lymphomas but the overall incidence is increased threefold. The histopathological morphology is that of a highly malignant mesenchymal neoplasm that closely resembles human fibrous histiocytoma. The tumor cells were classified as myelomonocytic on the basis of several lineage-specific markers and the lack of rearrangements of the immunoglobulin heavy chain and the T cell receptor beta loci. Cultured tumor cells produce macrophage colony stimulating factor (M-CSF) protein and express the M-CSF receptor, suggesting the involvement of an autocrine loop in this malignancy. Similar to the E mu L-myc T cell lymphomas, these tumors show high-level transgene expression but no detectable levels of endogenous c-myc mRNA, directly implicating the deregulated expression of L-myc in the generation of this malignancy. E mu L-myc myelomonocytic tumors show consistent trisomy of chromosome 16, implicating this as a secondary event in the development of this tumor. In the light of recent findings that L-myc is expressed in human myeloid leukemias and in several human myeloid tumor cell lines, the results described here might implicate L-myc in the development of naturally occurring myeloid neoplasias. PMID- 1310100 TI - Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. AB - The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TNF activity; at high concentrations, the sTNF-Rs indeed inhibit TNF effects. However, we report here that in the presence of low concentrations of the sTNF-Rs, effects of TNF whose induction depend on prolonged treatment with this cytokine are augmented, reflecting an attenuation by the sTNF-Rs of spontaneous TNF activity decay. Evidence that this stabilization of TNF activity by the sTNF-Rs follows from stabilization of TNF structure within the complexes that TNF forms with the sTNF Rs is presented here, suggesting that the sTNF-Rs can affect TNF activity not only by interfering with its binding to cells but also by stabilizing its structure and preserving its activity, thus augmenting some of its effects. PMID- 1310102 TI - Long-term follow-up on National Cancer Institute Phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation. AB - PURPOSE: We report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd). METHODS: For a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow up) or until death. RESULTS: The results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation. CONCLUSION: The failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM. PMID- 1310101 TI - Biochemical evidence for the rapid assembly and disassembly of processed antigen major histocompatibility complex class II complexes in acidic vesicles of B cells. AB - Helper T cell recognition of antigen requires that it be processed within antigen presenting cells (APC) to peptide fragments that subsequently bind to major histocompatibility complex (MHC) class II molecules and are displayed on the APC surface. Heretofore, processed antigen-MHC class II complexes have been detected by functional assays, measuring the activation of specific T cells. We now report direct, biochemical evidence for the assembly of processed antigen-MHC class II complexes within splenic B cells as APC. The I-Ek MHC class II molecules were immunoprecipitated from B cells that had processed the model protein antigen cytochrome c radiolabeled across its entire length by reductive methylation of lysine residues and covalently coupled to Ig-specific antibodies, allowing internalization after binding to surface Ig. Our previous studies showed that I Ek immunoaffinity purified from B cells that had processed cytochrome c contains functional processed antigen--MHC class II complexes and that approximately 0.2% of the I-Ek molecules are specifically associated with one of two predominant processed antigenic fragments. Here we show that these complexes are rapidly assembled, within 30-60 min after antigen binding to surface Ig on splenic B cells. Maximal numbers of complexes are assembled by 2 h in a process that is sensitive to acidic vesicle inhibitors but not to inhibitors of protein synthesis. The processed antigen-I-Ek complexes have a relatively short half-life of 2-4 h and are disassembled or degraded within 8 h after antigen is first internalized. The disassembly or degradation of the processed antigen-I-Ek complexes requires acidic vesicle function, and in the presence of an acidic vesicle inhibitor the complexes are long lived. Thus, using a biochemical assay to monitor processed antigen-I-Ek complexes, we find that, in B cells, processed antigen is relatively rapidly associated in acidic vesicles with preexisting MHC class II molecules, and the complexes are disassembled 4-6 h later in processes that also require acid vesicle function. PMID- 1310103 TI - Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. AB - PURPOSE: The trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone. PATIENTS AND METHODS: In this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP). RESULTS: There were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non statistically significant trend toward a longer median time to progression with alternating therapy (4.3 months, 4.0 months, 5.2 months, respectively). Crossover second-line chemotherapy given at progression produced low response rates and short survival, regardless of the regimen used. Myelosuppression was the dose limiting toxicity for all patients, although the pattern and severity differed among the treatment arms. CONCLUSIONS: The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant. Alternating therapy provides no therapeutic advantage compared with the use of either of these regimens alone and should not be considered as standard treatment in this clinical setting. PMID- 1310104 TI - Prolonged administration of oral etoposide in non-small-cell lung cancer: a phase II trial. AB - PURPOSE: The trial was undertaken to investigate the activity and toxicity of a prolonged schedule of oral etoposide in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between March 1989 and August 1990, 25 patients with advanced NSCLC were treated with oral etoposide 50 mg/m2/d for 21 consecutive days, repeated every 28 to 35 days. The median patient age was 60 years (range, 38 to 84 years); male:female ratio was 12:13. Eight patients had stage IIIB disease; 17 had stage IV. Seventy-six percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. No patient had received previous chemotherapy with standard agents; nine patients had received previous or concurrent radiation therapy. Plasma etoposide concentrations were measured to estimate etoposide bioavailability and kinetics. RESULTS: Five of 22 patients (23%; 95% confidence interval [CI], 10% to 43%) had partial responses. Median response duration was 5 months (range, 2 to 6 months). Four of five responders were female. Besides alopecia, which occurred in all patients, myelosuppression was the most common toxicity, but was mild or moderate in most patients. Median leukocyte nadir during course 1 was 3,200/microL; only four of 69 courses produced a leukocyte nadir less than 1,000/microL. Severe thrombocythemia (less than 75,000/microL) did not occur. Gastrointestinal toxicity was uncommon. Median peak etoposide concentration was 3.4 micrograms/mL. A mean serum etoposide concentration greater than 1 microgram/L was maintained for more than 13 hours; the plasma concentration-time curve (AUC) was estimated to be 90% of that predicted after an identical dose of etoposide given intravenously. CONCLUSIONS: Etoposide given by this dose and schedule has moderate activity as first-line systemic therapy for advanced NSCLC. In previously untreated patients, chronic oral etoposide is well tolerated, and incorporation into combination regimens should be feasible. Etoposide bioavailability may be increased at lower oral doses. PMID- 1310105 TI - Phase I-II study of high-dose epirubicin in advanced non-small-cell lung cancer. AB - PURPOSE: A phase I multicenter trial was performed to determine the maximum tolerated dose (MTD) of epirubicin, given on 3 consecutive days every 3 weeks to previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: After appropriate staging and a baseline multiple-gated angiogram (MUGA) scan, at least four patients were entered at each dose level, starting at 35 mg/m2 of epirubicin given intravenously (IV) daily for 3 days (105 mg/m2) and escalating by 5 mg/m2 per injection in each dose level (15 mg/m2 per course). Epirubicin was administered up to a maximum dose of 60 mg/m2/d for 3 days (180 mg/m2). The MTD was determined to be 55 mg/m2/d for 3 days (165 mg/m2) after treating a total of 35 (33 assessable) patients. Nadir granulocyte counts and associated febrile episodes comprised the dose-limiting toxicity, but there were no treatment-related deaths. A phase II trial was performed using a dose of 50 mg/m2/d for 3 days (150 mg/m2) every 3 weeks with no dose escalation, but with dose reduction for toxicity as required. A total of 30 patients were entered onto this phase of the study. RESULTS: The major toxicity, as in the phase I trial, was neutropenia with five febrile episodes, again with no treatment-related deaths. An overall response rate of 12 of 63 (19%) was noted in the combined patient population of the phase I-II trial, with 95% confidence intervals of 10% to 31%. When the response rate was analyzed by histology, only one of 17 (6%) patients with squamous histology, as compared with 11 of 46 (24%) with non squamous histology, responded, but this did not reach statistical significance (P = .15). CONCLUSIONS: High-dose epirubicin is tolerable and is an active single agent in NSCLC. It should be combined with relatively nonmyelosuppressive agents such as cisplatin to try to obtain higher response rates and extend the survival in this disease. PMID- 1310106 TI - Radionuclide hysterosalpingography with technetium-99m-pertechnetate: application and radiation dose to the ovaries. AB - Although radionuclide hysterosalpingography (RNHSG) has been suggested as an efficient procedure for assessing function of fallopian tubes, the radiation dose to the ovaries was addressed as an important issue to be taken into consideration. We describe a modified method of RNHSG, calculating the radiation dose to the ovaries. A small dose of approximately 18.5 MBq (0.5 mCi) of [99mTc]pertechnetate was administered directly into the uterine cavity without overpressure. The accuracy of the method was 84.5% as compared with the contrast hysterosalpingography. The estimated average dose to the ovaries was 0.057 mGy/MBq (0.21 rad/mCi) or 1.08 mGy (108 mrad) per study. RNHSG is an accurate method for functional study of fallopian tube patency with low radiation dose. PMID- 1310107 TI - Postprandial lipid response following a high fat meal in rats adapted to dietary fiber. AB - Rats were adapted to diets containing 5 g/100 g cellulose (CL), 5 g/100 g oat bran fiber (OB) or 5 g/100 g psyllium husk (Psy) for 4 wk. Following a 12-h fast, animals were either killed at 0 h (baseline) or fed 4.5 g of a test meal that provided 50% energy from fat, then killed at 1, 4 or 6 h postprandially. Fasting plasma and HDL cholesterol concentrations were lower in Psy-fed animals than in rats fed either CL or OB. Plasma triglycerides increased significantly from baseline (0 h) in all groups but did not differ among diet treatments. Increases in triglyceride content of the treatments. Increases in triglyceride content of the chylomicron/VLDL fraction occurred in the CL- and OB-fed groups and in the HDL fraction of the Psy-fed group during the postprandial period. In unfed animals the hepatic and intestinal levels of apolipoprotein A-IV mRNA were higher in the CL-fed group than in the groups fed OB and Psy. Apolipoprotein B mRNA was higher in the intestine of the OB-fed group than in the groups fed CL and Psy and had a significant gradient along the small intestine, increasing in the distal third. The results suggest that chronic consumption of fiber is less likely to modify the acute plams triglyceride response to a fat-containing test meal than if a fiber supplement is incorporated into the meal. PMID- 1310108 TI - Dietary soluble fiber and cholesterol affect serum cholesterol concentration, hepatic portal venous short-chain fatty acid concentrations and fecal sterol excretion in rats. AB - Sprague-Dawley rats were fed diets containing 7.5% dietary fiber as cellulose (control), pectin, psyllium or oat bran with or without 0.3% added cholesterol for 3 wk. Among rats fed cholesterol, liver total lipid and cholesterol concentrations were significantly lower in groups fed pectin, psyllium and oat bran compared with cellulose-fed controls. Cholesterol feeding resulted in significantly greater liver cholesterol in rats fed cellulose, psyllium and oat bran but not in those fed pectin. Among rats fed cholesterol, total serum cholesterol levels were significantly lower in those fed pectin than in those fed psyllium, oat bran or cellulose. When cholesterol was fed, the oat bran-fed group had significantly higher butyrate and the pectin-fed group had significantly higher propionate concentrations in the hepatic portal vein than did cellulose fed controls. The groups fed psyllium, oat bran and pectin all had significantly higher fecal neutral sterols than did the cellulose-fed group when cholesterol was fed. Without dietary cholesterol only pectin-fed rats had significantly higher fecal excretion of neutral sterols than those fed cellulose. Dietary fiber did not influence fecal acidic sterol excretion. However, the addition of cholesterol to these fiber diets was accompanied by a significantly higher bile acid excretion than that of animals fed cellulose without cholesterol. The results of this study indicate that soluble dietary fibers may exert their hypocholesterolemic effect by increasing excretion of fecal neutral sterols. PMID- 1310109 TI - Various dietary fibers have different effects on lipase-catalyzed hydrolysis of tributyrin in vitro. AB - The ability of various dietary fibers to impede lipase-catalyzed hydrolysis of tributyrin was studied in vitro. Conditions (temperature, kind and concentration of constituents, pH, agitation) were chosen to mimic, as closely as possible, those prevailing in the human duodenum. Lipolysis was monitored at pH 6.0 and 37 degrees C using a constant pH titrimeter. Some fibers inhibited lipolysis (red wheat bran, white wheat bran, oat bran and sugarbeet fiber), whereas most did not (psyllium seed, pectin LM 12CG, carrageenan, carboxymethylcellulose, gum arabic, and pectin slow set). Water extracts of the fibers accounted for 32-41% of the inhibitory effect of the two wheat brans on lipolysis and 100% of the inhibitory effect of oat bran. PMID- 1310110 TI - The metabolizable energy of diets differing in dietary fat and fiber measured in humans. AB - The metabolizable energy of two diets differing in fat and fiber content was measured in balance experiments in 42 adult male subjects. Subjects received each diet for 10 wk in a crossover design. Average fiber consumption from mixed sources (cereals, legumes, fruits and vegetables) while consuming the low fiber, high fat diet was 34 g/d and 64 g/d while consuming the high fiber, low fat diet. The percentages of energy from protein, fat and carbohydrate were 16, 18.5 and 65.5, respectively in the high fiber, low fat diet and 14.5, 36 and 49.5, respectively, in the low fiber, high fat diet. Seven-day composite collections of food, urine and feces were made during the 10th wk of the study. The freeze-dried food and fecal samples were analyzed for total energy content and for protein, fat, moisture, ash and carbohydrate. Urine samples were analyzed for nitrogen and energy content. The digestibility of the energy-containing nutrients was significantly lower when subjects were consuming high fiber, low fat vs. low fiber, high fat diets (95.4 vs. 97.0, carbohydrate; 92.5 vs. 95.5, fat; 83.7 vs. 89.4, protein; and 91.4 vs. 94.3, energy. PMID- 1310111 TI - Epithelia-damaging virus infections affect vitamin A status in chickens. AB - The effect of infection with infectious bronchitis virus (IBV) and reovirus (RV) on vitamin A status was investigated in chickens with a normal or marginal intake of vitamin A. At the age of 4 wk, chickens were infected with either IBV or RV, primarily affecting the respiratory or intestinal tract, respectively. Both viruses lowered plasma retinol levels significantly. The effect was more pronounced in chickens fed a diet marginally deficient in vitamin A than in those fed a diet adequate in vitamin A. Concentrations of retinol-binding protein, transthyretin and albumin in RV-infected chickens were also significantly lower than in noninfected chickens fed the same diets; in chickens infected with IBV, there was no effect. These results suggest that the reduced vitamin A status of IBV-infected chickens could be attributed to increased rate of utilization by tissues. In RV infection, this mechanism could be involved but impaired absorption of nutrients (including vitamin A) and direct loss of nutrients via the intestinal tract could also be important. PMID- 1310112 TI - Dietary fat and cholesterol modulate the plasma lipoprotein distribution and production of pigment or cholesterol gallstones in hamsters. AB - To evaluate the impact of key dietary factors on plasma lipoproteins and gallstone induction, male Syrian hamsters were fed either cholesterol and fat supplemented purified diets containing glucose or lactose, or cholesterol and fat free diets with or without fiber, for 13 wk. Fat-supplemented hamsters were hyperlipidemic in comparison to those fed fat-free diets. The former group revealed a greatly expanded VLDL fraction, whereas a normal HDL2 pool predominated in the latter group. Plasma fatty acids indicated that hamsters fed the fat-free diet were essential fatty acid deficient whilst the hamsters fed the fat-supplemented diet were subnormal in essential fatty acids. Ninety-three percent of the hamsters fed the fat-supplemented diet had gallstones (mostly cholesterol), whereas 62% of hamsters fed the fat-free diet had gallstones (almost all pigmented). Lactose increased cecal weight and prevented pigment stone formation in the fat-supplemented hamsters, whereas adding fiber to the fat free diet contributed essential fatty acids, eliminated cholesterol stones and enhanced pigment stone formation. Thus, diets containing casein, rice flour, glucose and fiber with minimal essential fatty acids but no cholesterol promoted pigment stones (associated with a normal lipoprotein profile); a low fat diet limited in essential fatty acids but containing cholesterol and lactose, promoted cholesterol gallstones (associated with an expanded VLDL pool). PMID- 1310113 TI - A novel class of cardiotonic agents: synthesis and biological evaluation of 5 substituted 3,6-dihydrothiadiazin-2-ones with cyclic AMP phosphodiesterase inhibiting and myofibrillar calcium sensitizing properties. AB - As part of a search for new cardiotonic agents significantly sensitising the myocardial contractile proteins to calcium, together with cardiac cyclic AMP-PDE inhibitory activity, we have discovered that novel 5-substituted 3,6 dihydrothiadiazin-2-ones may fulfill both properties. The sensitising effect of the contractile proteins to calcium, assessed by the shift in the calcium sensitivity of canine cardiac myofibrillar magnesium-dependent ATPase, is determined by steric and electronic requirements. The requirements for phosphodiesterase inhibition, especially that of a near-planar arrangement for the phenyl and thiadiazin-2-one ring are consistent with those already described for analogous pyridazinones. The synthesis and structure-activity relationships are discussed. PMID- 1310114 TI - Synthesis, characterization, and biological evaluation of a novel class of N (arylethyl)-N-alkyl-2-(1-pyrrolidinyl)ethylamines: structural requirements and binding affinity at the sigma receptor. AB - By synthesizing and testing a part-structure, N-[2-(3,4-dichlorophenyl)ethyl]-N methyl-2-(1-pyrrolidinyl)ethylamine (3), derived from our previously reported high affinity sigma receptor ligands (1S,2R)-(-)-N-[2-(3,4-dichlorophenyl)-ethyl] N-methyl-2-(1- pyrrolidinyl)cyclohexylamine [(-)-2] and (+)-2, we have identified a novel class of superpotent (subnanomolar affinity) sigma ligands specific for the sigma receptor labeled by [3H]-(+)-3-PPP. When 3 was tested for its capacity to displace [3H]-(+)-3-PPP from guinea pig brain membranes, it exhibited a Ki of 0.34 nM, which is better than either of its parent compounds (-)-2 (Ki = 1.3 nM) and (+)-2 (Ki = 6.0 nM). Other compounds related to 3 such as N-[2-(3,4 dichlorophenyl)ethyl]-N-methyl-2-(1-homopiperidinyl)ethy lamine (19) exhibited Ki = 0.17 nM [( 3H]-(+)-3-PPP). The determinants for high sigma receptor affinity of 3 were examined by manipulation of this structure in a number of different ways. The high efficacy of these compounds for the sigma receptor, their relative chemical simplicity and ease of synthesis, and their high degree of selective identifies N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) and related compounds as a highly promising base for determination of the functional role of sigma receptors as well as the development of novel therapeutic agents. PMID- 1310115 TI - Synthesis, antinociceptive activity, and opioid receptor profiles of substituted trans-3-(decahydro- and octahydro-4a-isoquinolinyl)phenols. AB - A series of trans-3-(6- and 7-substituted-decahydro-4a-isoquinolinyl)phenols and trans-3-(octahydro-4a-isoquinolinyl)phenols have been synthesized as potential opioid analgesics. Using a combination of in vitro and in vivo test systems, the receptor profiles of selected compounds have been assessed and in some instances distinguish between mu- and kappa-receptor agonists. In general, introduction of a 6-exocyclic methylene group into the trans-3-(decahydro-4a-isoquinolinyl)phenol system enhanced both antinociceptive activity and kappa-opioid receptor selectivity. For each series, analogues bearing an N-cyclopropylmethyl substituent exhibited greater kappa-receptor selectivity while N-methyl derivatives showed greater mu-receptor selectivity. The 7-substituted compounds (3b) were significantly less potent antinociceptive agents than their 6 substituted counterparts (3a), the octahydroisoquinoline analogues exhibiting intermediate activity. The axial 8-methyl-6-exocyclic methylene isoquinoline (20) is the most potent compound in the mouse abdominal constriction assay (ED50 = 0.05 mg/kg sc), whereas the equatorial 8-methyl isomer (16) was significantly less potent (ED50 = 3.3 mg/kg sc). PMID- 1310116 TI - Synthesis and antibacterial activity of new tetracyclic quinolone antibacterials. AB - A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H- thiazolo[3,2 a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 6l showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6l. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidino, morpholino, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 6l also showed potent in vivo antibacterial activity against Gram positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the carboxy group by a sulfonic acid group in 6l resulted in a complete loss of antibacterial activity. PMID- 1310117 TI - Beta-proline analogues as agonists at the strychnine-sensitive glycine receptor. AB - 3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy 3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine-sensitive glycine receptor. PMID- 1310118 TI - Substituted 4,6-diaminoquinolines as inhibitors of C5a receptor binding. AB - The anaphylatoxin C5a is implicated in a number of inflammatory diseases. It is a highly cationic protein with 13 of 74 amino acids being either arginine or lysine. A search focusing on positively charged molecules, particularly amine containing functionalities, led to the discovery of substituted 4,6 diaminoquinolines 1 [N,N'-bis(4-amino-2-methyl-6-quinolyl)urea] and 7 [6-N-(2 chlorocinnamoyl)-4,6-diamino-2-methylquinoline] as inhibitors of C5a receptor binding. These two compounds inhibited the binding of radiolabeled C5a to its receptor isolated from human neutrophils with IC50's = 3.3 and 12 micrograms/mL, respectively. Our efforts to enhance their potencies by chemical modification revealed a narrow profile of potency for effective C5a receptor binding inhibition. PMID- 1310119 TI - Potential antitumor agents. 64. Synthesis and antitumor evaluation of dibenzo[1,4]dioxin-1-carboxamides: a new class of weakly binding DNA intercalating agents. AB - A series of substituted dibenzo[1,4]dioxin-1-carboxamides has been synthesized and evaluated for in vitro and in vivo antitumor activity. The required substituted dibenzo[1,4]dioxin-1-carboxylic acids were prepared by a variety of methods. No regiospecific syntheses were available for many of these, and separation of the mixtures of regioisomers obtained was sometimes difficult. The dibenzo[1,4]dioxin-1-carboxamides are active against wild-type P388 leukemia in vitro and in vivo, with structure-activity relationships resembling those for both the acridine-4-carboxamide and phenazine-1-carboxamide series of DNA intercalating antitumor agents. In all three series, substituents placed peri to the carboxamide sidechain (the 5-position in the acridines, and the 9-position in the phenazines and dibenzo[1,4]dioxins) enhance activity and potency. The 9 chlorodibenzodioxin-1-carboxamide was also curative against the remotely sited Lewis lung carcinoma. Several of the compounds showed much lower levels of cross resistance to the P388/AMSA line than classical DNA-intercalating agents, which suggests that their primary mechanism of action may not be via interference with topoisomerase II alpha. This is of interest with regard to the development of drugs to combat resistance mechanisms which arise by the expression of the topo II beta isozyme. PMID- 1310120 TI - Structure-function studies of peptides inhibiting the ribonucleotide reductase activity of herpes simplex virus type I. AB - Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2 (298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex virus (HSV) type I and II ribonucleotide reductase R2 protein and is 15 times more potent than the latter in its in vitro inhibition of HSV-1 reductase activity. Accordingly, a new series of analogues based on this structure was studied in vitro. The replacement of Asp305 by Asn, Glu, Gln, Ser, or Cys; of Asn304 by Gln or Ser; of Ile303 and Val302 by D-Val; and of Tyr298 by Cha induced an important loss of inhibitory potency. The substitution of Asn304 by Asp; of Thr301 by Cys, Ser, or Val; of Gly300 by Ala or Val; of Ala299 by Val; or of Tyr298 by homoPhe, 4'-fluoro-Phe, 4'-chloro-Phe, 3'-iodo-Tyr, Me-Tyr, or For-Trp led to a moderate decrease of the Ac-VZV R2-(298-306) potency. The replacement of Val302 by Ile; Ala299 by Cys, Ser, or Thr; or the insertion of a six- or eight carbon chain between Tyr298 and the NH2 terminus either preserved or slightly increased the inhibitory potency of Ac-VZV R2-(298-306). Finally, the substitution of Tyr298 by Trp or the addition of 4'-nitro-Phe at the amino terminus resulted in a 3-fold increase of potency. Altogether, these results stress the importance of the structural integrity of the minimum active core 302 306 in preserving the inhibitory potency and suggest that further studies on monosubstitutions could be directed at the portion 298-301 of the peptide. PMID- 1310122 TI - Detection of human papillomavirus in squamous neoplasm of the penis. AB - Infection of the external human urogenital system with human papillomavirus has been implicated with the development of genital cancer. A modified polymerase chain reaction technique has been used to evaluate type specific deoxyribonucleic acid (DNA) sequences of unique E6 to E7 transforming regions of human papillomavirus genomes (types 6b/11, 16 and 18) in a morphological spectrum of in situ (carcinoma in situ) and invasive neoplasm of the penis. We studied 15 examples of carcinoma in situ [7 bowenoid and 8 nonbowenoid (squamoid or simplex)], 11 of invasive squamous carcinoma, 1 of verrucous carcinoma, 2 of verrucous hyperplasia, 1 of urethral adenocarcinoma and 1 solitary papilloma. Viral DNA was not detected in any of the nonbowenoid specimens of carcinoma in situ, the verrucous carcinoma, the adenocarcinoma or the papilloma of the penis. Human papillomavirus types 6b/11 and 18 specific sequences also were not detectable in any of the specimens examined. However, all 7 of the bowenoid forms of carcinoma in situ were positive for human papillomavirus type 16 DNA. The presence of human papillomavirus type 16 was also detected in 9 of 11 invasive squamous carcinomas and in both verrucous hyperplasias. Our results confirm that the bowenoid forms of intraepithelial neoplasms and most invasive squamous carcinomas contain the E6 to E7 portion of type 16 human papillomavirus genome. PMID- 1310121 TI - Synthesis of novel 2-phenyl-2H-pyrazolo[4,3-c]isoquinolin-3-ols: topological comparisons with analogues of 2-phenyl-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H) ones at benzodiazepine receptors. AB - Based on the topology of pyrazoloquinolinones 10-12, a series of 2-phenyl-2H pyrazolo[4,3-c]isoquinolines 6a-d, 7a-d, 8, and 9 have been synthesized and evaluated for their ability to inhibit radioligand binding to benzodiazepine receptors (BzR). Modification of the hydrogen bonding donor and acceptor characteristics of the NH and C = O functionalities of the pyrazoloquinolinones 10-12 resulted in ligands with dramatically reduced affinities (IC50 much greater than 2 microM) for BzR. The low affinities of 6a-d, 7a-d, 8, and 9 are consistent with the involvement of the NH function present on diverse classes of inverse agonists (beta-carbolines, diindoles, and pyrazoloquinolinones) with a hydrogen bond acceptor site (A2) on the binding protein. Moreover, it supports the involvement of the carbonyl function of the pyrazoloquinolinones and the pyridine nitrogen atom of beta-carbolines and diindoles with a hydrogen bond donor site (H1). Finally, the results from this work indicate that a simultaneous interaction at both hydrogen bond donor (H1) and acceptor sites (A2) at BzR is required for high affinity binding of inverse agonists. PMID- 1310123 TI - Secondary surgery in patients with malignant germ cell tumors. AB - A total of 102 men treated for germ cell tumor with chemotherapy containing cisplatin was referred for a secondary operation with signs of tumor in the retroperitoneum or chest. Of the patients 85 underwent laparotomy, 14 underwent thoracotomy and 3 had both operations. Residual tumors were completely resected in 66 patients and incompletely resected in 30, while no tumor was found in 6. The resected specimen was malignant in 18 patients, of whom 11 had complete removal of all malignant tissue. All patients with malignancy in the resected specimen received further chemotherapy. Long-term disease-free status was obtained in 75% of those patients who had a complete resection, compared with 14% in the group with incomplete resection. There was no evidence of malignant disease at operation in 78 patients but 5 of them later died of the disease. Malignant tissue was present in the residual tumor in only 1 of 15 patients whose primary tumor was seminoma alone. Resection was attempted in 14 patients despite abnormal tumor markers preoperatively. Only 5 of these patients achieved a disease-free status and 2 of them died later of malignant disease. Over-all 79 of the 102 patients are without evidence of disease (medium postoperative observation 23 1/2 months). We conclude that a secondary operation constitutes an important part of the treatment of patients with germ cell cancer. PMID- 1310124 TI - Retroaortic left renal vein in testicular cancer patient: potential staging and treatment pitfall. AB - A 20-year-old man was diagnosed with a left mixed germ cell testicular tumor and clinical staging with computerized tomography suggested left para-aortic subhilar retroperitoneal adenopathy. The patient received 4 cycles of cisplatin, vinblastine and bleomycin chemotherapy but the mass in the left renal hilus area remained unchanged. Subsequent retroperitoneal lymphadenectomy revealed the mass to be a retroaoritc left renal vein type 2. Further confusion occurred during followup in differentiating this anomaly from recurrent neoplasm necessitating evaluation by magnetic resonance imaging. Retroaortic left renal vein represents a potential imaging pitfall in testicular cancer that may facilitate suboptimal staging, treatment and followup. PMID- 1310125 TI - Tetrodotoxin protects against acute ischemic renal failure in the rat. AB - Tetrodotoxin has been reported to cause prolonged systemic hypotension without resultant ischemic damage. We tested its ability to protect the kidney during 60 minutes of warm ischemia in uninephrectomized rats. Protection was observed when tetrodotoxin was given intravenously at two microgram./kg. and four microgram./kg. as assessed by serial plasma blood urea nitrogen and creatinine measurements over two weeks. Tetrodotoxin was protective when given immediately before or immediately after the ischemic period. The renal protection of tetrodotoxin was not due to its effects on renal nerves as renal denervation did not protect the kidney from the ischemic damage. The renal protective effects of four microgram. tetrodotoxin/kg. were similar to those of four mg. captopril/kg. but the combination of the two was paradoxically without effect. We tested whether tetrodotoxin and captopril chemically antagonized each other, but in the presence of tetrodotoxin, captopril was still a potent inhibitor of the conversion of angiotensin I to angiotensin II. These results indicate that tetrodotoxin could be useful in elucidating the sequence of events associated with ischemic-reperfusion renal injury and in identifying ways of preserving renal function during renal surgery. PMID- 1310126 TI - Presumptive use of bicarbonate in cardiopulmonary resuscitation. PMID- 1310127 TI - Therapeutic aspects of myelodysplastic syndromes in chronic phase. AB - Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases. PMID- 1310130 TI - Enhanced sensitivity to naltrexone is associated with an up-regulation in GABA receptor function. AB - Rats were made sensitive to the effects of the opioid antagonist naltrexone by treating them once weekly with cumulative doses of the drug (1, 3, 10, 30 and 100 mg/kg). Sensitization was monitored by measuring salivation following naltrexone administration. During the first week of treatment, no salivation was noted following any dose of naltrexone. Over a period of 8 weeks, however, increasing amounts of salivation were noted, with the most salivation occurring at the higher doses. Animals treated for 8 weeks with saline never salivated following injections. Following the development of sensitivity to naltrexone, the rats were sacrificed and their brains were assayed for GABA receptor function. GABA stimulated chloride uptake, a measure of GABA receptor function, was unchanged in the cortex, but was increased in the cerebellum. These results suggest that the effects of naltrexone on cerebellar GABA receptors may be involved in the development of enhanced sensitivity to opioid antagonists. PMID- 1310128 TI - PAF receptor blockade inhibits lung vascular changes in the rat monocrotaline model. AB - We recently reported that platelet-activating factor (PAF) levels increased in lung tissue after 1 subcutaneous injection of monocrotaline (MCT) (which causes lung injury), and, further, that treatment with PAF antagonists reduced pulmonary hypertension in this chronic lung injury rat model [15]. In the present study, we examined the effect of WEB 2170, a specific PAF antagonist, on MCT-induced pulmonary vascular remodeling. At 3 weeks after MCT injection, pulmonary hypertension in the animals was associated with an increase in the vessel wall thickness of the muscular arteries, reduction in number of peripheral arterioles, and right ventricular hypertrophy. In WEB 2170-treated rats, these changes were significantly less severe when compared with those observed in MCT-treated rats. In MCT-treated rats, there were significant increases in in vitro [3H]thymidine incorporation and accumulation of hydroxyproline in the lung tissue, and these changes were inhibited by WEB 2170 treatment. Our results suggest that PAF or a PAF-dependent sequence of events is involved in MCT-induced lung vascular remodeling. PMID- 1310129 TI - Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognosis. AB - Between 1975 and 1985, 25 patients with metastatic bronchioloalveolar carcinoma and 223 patients with metastatic adenocarcinoma of the lung received experimental cisplatin-based chemotherapy at the Mayo Clinic. The chemotherapeutic response rates were 32% and 33%, respectively. The median times to progression of disease were identical (3 months in both groups). The median survival times were 4 months and 6 months, respectively. Metastatic bronchioloalveolar carcinoma is an aggressive disease that is associated with a poor prognosis, similar to metastatic adenocarcinoma of the lung. PMID- 1310131 TI - Identification of cultured cells selectively expressing Y1-, Y2-, or Y3-type receptors for neuropeptide Y/peptide YY. AB - Neuropeptide Y (NPY) and peptide YY (PYY) are homologous 36 amino acid amidated peptides that often, but not always, exert similar actions and binding profiles. The present study of cultured cells confirms that both peptides as well as radioiodinated analogs, i.e. 125I-Bolton-Hunter-NPY (125I-BH-NPY) and 125I peptide YY (125I-PYY), show high affinity to binding sites/receptors of the previously proposed Y1- and Y2-subtypes, selectively expressed by the human neuroblastoma cell lines, SK-N-MC and SK-N-BE(2), respectively. In contrast, bovine adrenal chromaffin cells did not bind 125I-PYY, while displaying high affinity 125I-BH-NPY sites, and may therefore represent a cell type expressing a recently proposed Y3-type of (NPY-preferring) receptors. Several non-labeled fragments/analogs have been used in displacement experiments to further characterize the structural requirements for Y1-, Y2-, and Y3-type binding. In every instance, specific binding was reduced by addition of 5' guanylylimidodiphosphate [Gpp(NH)p], indicating that the three receptor subtypes belong to the G-protein-coupled superfamily of receptors. Moreover, in both neuroblastoma cell lines, the peptides elicited, with appropriate orders of potency, reduction of forskolin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. Finally, NPY-evoked 45Ca2+ influx was observed in SK-N-MC and in chromaffin cells. A common dual coupling mechanism of NPY/PYY receptors, i.e. to reduction of cAMP and to Ca2+ elevation, is therefore suggested to exist, although both phenomena could not be demonstrated in every cell type. PMID- 1310132 TI - Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. AB - We describe novel potent endothelin (ET) antagonists that are highly potent and selective for the ETA receptor (selective to ET-1). Of the synthetic analogs based on ETA antagonist BE-18257A isolated from Streptomyces misakiensis (IC50 value for ETA receptor on porcine aortic smooth muscle cells (VSMCs); 1.4 microM), the compounds BQ-123 and BQ-153 greatly improved the binding affinity of [125I]ET-1 for ETA receptors on VSMCs (IC50; 7.3 and 8.6 nM, respectively), whereas they barely inhibited [125I]ET-1 binding to ETB receptors (nonselective with respect to isopeptides of ET family) in the cerebellar membranes (IC50; 18 and 54 microM, respectively). Associated with the increased affinity for ETA receptors, these peptides antagonized ET-1-induced constriction of isolated porcine coronary artery. However, there was a small amount of ET-1-induced vasoconstriction resistant to these antagonists, which paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the aortic smooth muscle layer. These data suggest that the artery has both ETA and ETB receptors responsible for ET-1-induced vasoconstriction. The antagonists shifted the concentration-response curve to the right for ET-1 in the coronary artery, and increased the apparent dissociation constant in the Scatchard analysis of [125I]ET-1 binding on the VSMCs without affecting the binding capacity, indicative of the competitive antagonism for ETA receptor. In conscious rats, pretreatment with the antagonists markedly antagonized ET-1-induced sustained pressor responses in dose-dependent fashion without affecting ET-1-induced transient depressor action, suggesting that the pressor action is mediated by ETA receptors, while the depressor action is mediated by ETB receptors. In addition, pretreatment with the potent antagonists prevented ET-1-induced sudden death in mice. Thus, these potent ETA antagonists should provide a powerful tool for exploring the therapeutic uses of ETA antagonists in putative ET-1-related disorders. PMID- 1310133 TI - Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys. AB - The blood level of erythropoietin (Epo) is often anomalously low in anemic patients with inflammatory or malignant diseases. Therefore, we studied effects of pure recombinant immunomodulatory peptides on Epo formation in cultures of the human hepatoma cell line, HepG2. Interleukin (IL)-1 beta, IL-1 alpha, and tumor necrosis factor alpha lowered Epo production with half-maximal inhibition at 2, 5, and 20 U/ml, respectively. IL-6, transforming growth factor beta 2 and interferon gamma did not inhibit. Furthermore, IL-1 beta (10 U/ml) proved to block Epo formation in isolated serum-free perfused rat kidneys. Proposedly, monokines play a role in the pathogenesis of Epo deficiency in various diseases. PMID- 1310134 TI - Pharmacological evidence for the involvement of multiple calcitonin gene-related peptide (CGRP) receptors in the antisecretory and antiulcer effect of CGRP in rat stomach. AB - We have investigated the effect of the C-terminal fragment of human calcitonin gene-related peptide (human-CGRP8-37), a CGRP antagonist, on alpha-CGRP and salmon Calcitonin (sCT)-induced inhibition of gastric acid secretion stimulated by pentagastrin (24 nmol kg-1 h-1 i.v.) and gastric lesions induced by acetylsalycilic acid (ASA; 25 mM) in rats anaesthetized with urethane. Close intra arterial infusion of alpha-CGRP (2-5 nmol kg-1) and sCT (5 nmol kg-1) produced a reduction in gastric acid hypersecretion induced by pentagastrin. The concomitant infusion with human-CGRP8-37 (10 nmol kg-1) reversed the effect of both agonists. ASA-ulcers were reduced in a dose-dependent manner by infusion of alpha-CGRP (1-2 nmol kg-1 i.a.), but not by sCT (10 nmol kg-1 i.a.). Human-CGRP8 37 at a dose of 10 nmol kg-1 i.a. was unable to reverse the alpha-CGRP antiulcer effect. An higher dose of human-CGRP8-37 (50 nmol kg-1 i.a.) showed agonistic properties reducing ASA ulcers. These results suggest that the inhibitory effects of alpha-CGRP on stimulated acid secretion and aspirin ulcers are mediated by different mechanisms and/or different receptors. PMID- 1310135 TI - Pharmacological characterization of a novel muscarinic partial agonist, YM796, in transfected cells expressing the m1 or m2 muscarinic receptor gene. AB - To investigate the pharmacological effect of a novel compound YM796, we performed radioligand binding experiments and correlative biochemical experiments using the transfected murine fibroblast B82 cells which expressed the m1 and m2 muscarinic receptor genes (cloned cell lines designated as LK3-3 and M2LKB2-2, respectively). [3H](-)methyl-3-quinuclidinyl benzilate [( 3H](-)MQNB) binding in these transfected cell lines was inhibited by different optical isomers of YM796 and other muscarinic drugs, atropine, pirenzepine, AF-DX 116, as well as selected agonists. (-)YM796, (+)YM796 and (+/-)YM796 inhibited [3H](-)MQNB binding in LK3 3 cells with Ki values of 16.4 microM, 30.1 microM and 21.8 microM and in M2LKB2 2 cells with Ki values of 52.0 microM, 108 microM and 77.1 microM, respectively. From functional assays we found the two isomers, (-)YM796 and (+)YM796 had different intrinsic activities for the M1 and M2 muscarinic receptors. (-)YM796 revealed agonistic activity: stimulation of [3H]IP1 accumulation in LK3-3 cells with an EC50 value of 26.5 microM, which was less efficacious (the Emax value was 5.6 times basal) than carbachol, a full agonist (the Emax value was 17.2 times basal). Interestingly, (-)YM796 did not show significant inhibition of cAMP formation in M2LKB2-2 cells except at extremely high concentrations (greater than 1mM). (+)YM796 exhibited no significant efficacy for the M1 and M2 muscarinic receptors. These results suggest that (-)YM796 represents a muscarinic partial agonist with functional selectivity for the M1 muscarinic receptors whereas (+)YM796 shows no efficacy for either M1 or M2 muscarinic receptors in these transfected cells. PMID- 1310136 TI - Dynamic control of inositol 1,4,5-trisphosphate-induced Ca2+ release: a theoretical explanation for the quantal release of Ca2+. AB - A theoretical model has been elaborated in order to describe the kinetics of Ca2+ release induced by inositol 1,4,5-trisphosphate (IP3). The model is based on the existence of a key molecule that controls the interconversion of open and closed forms of the Ca2+ channel. The model can quantitatively explain the previously obtained experimental observations that showed that a continuous IP3 stimulus leads to a biphasic Ca2+ release and that successive IP3 additions provoke repetitive bursts of Ca2+ release. Other published interpretations of these observations are discussed. PMID- 1310138 TI - Slow voltage-dependent block of sodium channels in crayfish nerve by dihydropyrazole insecticides. AB - Previous current-clamp work has shown that dihydropyrazole insecticides block sodium channels in tonic sensory receptors and in axons depolarized by high K+ external solutions and that hyperpolarization removes the block [Pestic. Sci. 28:389-411 (1990)]. Voltage-clamp studies on internally perfused crayfish giant axons were done to confirm and extend these observations. At -100 mV dihydropyrazoles had little effect on the sodium current, but at more depolarized potentials they blocked it from either face of the membrane. The onset of block following a holding potential change or during wash-in of a dihydropyrazole was very slow, with a time constant of several minutes, and, although block could be removed with a similar time course by hyperpolarization, the effects of the insecticides could not be reversed by prolonged washing. Dihydropyrazoles did not affect delayed rectifier potassium currents in the axon. The voltage-dependent block could be described as a uniform shift of the steady state (slow) sodium inactivation (S infinity) curve in the direction of hyperpolarization, indicative of selective binding to inactivated states of the channel. Using hyperpolarizing prepulses to remove slow inactivation, block of sodium channels by dihydropyrazoles could be measured directly at holding potentials as positive as 50 mV, and it could be demonstrated that block saturated near -70 mV, consistent with a dependence on slow inactivation. The data were fit to a model tha assumes the dihydropyrazole binds to the slow-inactivated state of the channel on a one to one basis. Dissociation constants obtained from this analysis were similar to those obtained from analysis of inhibition of the binding of [benzoyl-2,5-3H] batrachotoxinin A 20-alpha-benzoate by the same dihydropyrazoles. In axons whose fast or slow inactivation gates had been removed by N-bromoacetamide or trypsin, respectively, dihydropyrazoles still blocked sodium current, indicating that dihydropyrazoles can block the channel as well as enhance the normal slow inactivation process. PMID- 1310137 TI - Luminal Ca2+ increases the sensitivity of Ca2+ stores to inositol 1,4,5 trisphosphate. AB - Ca2+ within intracellular stores has been proposed to act with cytosolic inositol 1,4,5-trisphosphate (InsP3) to cause opening of the integral Ca2+ channel of the InsP3 receptor, leading to mobilization of intracellular Ca2+ stores [FEBS Lett. 263:5-9 (1990)]. We have tested that suggestion in saponin-permeabilized rat hepatocytes by manipulating the Ca2+ content of the stores and then determining their sensitivity to InsP3, while keeping the cytosolic Ca2+ concentration constant. Stores depleted of Ca2+ by incubation with ionomycin were significantly less sensitive to InsP3, an effect thought likely to result from the decrease in luminal free Ca2+ concentration rather than from direct effects of ionomycin on InsP3 binding or Ca2+ permeability. The luminal free Ca2+ concentration of stores loaded in the presence of pyrophosphate appeared to be substantially reduced, and again there was a significant inverse correlation between the estimated free Ca2+ concentration of the stores and their sensitivity to InsP3. By following the kinetics of 45Ca2+ uptake into empty stores in the presence of inositol trisphosphorothioate, a stable InsP3 analogue, we demonstrated that stores respond to inositol trisphosphorothioate only after their luminal free Ca2+ concentration exceeds a critical level. We conclude that InsP3 and luminal Ca2+ together regulate Ca2+ mobilization from intracellular stores, and we discuss some of the implications of this interaction for the complex Ca2+ signals evoked by extracellular stimuli. PMID- 1310139 TI - Angiotensin II receptor recognized by DuP753 regulates two distinct guanine nucleotide-binding protein signaling pathways. AB - The 7315c cell, derived from a rat anterior pituitary tumor, expresses an angiotensin II (AII) receptor. [3H]AII binds to 7315c membranes specifically and saturably (Kd = 2.1 +/- 0.6 x 10(-6) M, Bmax = 282 +/- 33 fmol/mg of protein). GTP diminished the affinity of the membranes for [3H]AII (Kd = 4.1 +/- 0.4 x 10( 9) M, Bmax = 210 +/- 26 fmol/mg of protein). [3H]AII binding was displaced by AII (Ki = 1.3 +/- 0.6 x 10(-9) M), angiotensin III (AIII) (Ki = 0.9 +/- 0.4 x 10(-9) M), and the nonpeptide AII antagonist DuP753 (Ki = 1.4 +/- 0.6 x 10(-8) M). In contrast, a second nonpeptide AII ligand, PD123177, did not compete for [3H]AII binding sites. In intact cells, AII and AIII stimulated inositol trisphosphate (IP3) production (EC50 = 1.1 +/- 0.6 x 10(-8) M and 1.1 +/- 0.5 x 10(-8) M, respectively); this response to AII was antagonized by DuP753 (Ki = 1.7 +/- 0.3 x 10(-7) M). Pertussis toxin treatment failed to affect the ability of AII to stimulate IP3 production. In a crude membrane preparation, GTP was required for maximal AII-induced IP3 stimulation; guanosine thio-diphosphate abolished the agonist-GTP stimulation of IP3 production, in a concentration-dependent fashion. AII and AIII also inhibited adenylyl cyclase (EC50 = 2.9 +/- 1.1 x 10(-8) M and 6.0 +/- 1.0 x 10(-8) M, respectively). DuP753 antagonized the inhibition by AII of adenylyl cyclase (Ki = 2.8 +/- 0.4 x 10(-8) M). PD123177 failed to antagonize AII-induced cyclase inhibition. Pertussis toxin treatment abolished the AII and AIII inhibition of adenylyl cyclase. GTP was required for AII-induced inhibition of adenylyl cyclase. These data suggest that, in 7315c cells, a single subtype of AII receptor, identified by DuP753, is capable of regulating two different guanine nucleotide-binding protein (G protein) signalling pathways; one G protein, which is insensitive to pertussis toxin, stimulates IP3 production and the other G protein, which is sensitive to pertussis toxin, inhibits adenylyl cyclase. PMID- 1310140 TI - Carbachol-induced decrease in thyroid cell adenylyl cyclase activity is independent of calcium and phosphodiesterase activation. AB - The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphosphoinositide hydrolysis, was studied in thyroid cells. Incubation of cultured dog thyroid cells with 10 microM carbachol for 2-4 hr reduced the subsequent thyrotropic hormone (TSH) stimulation of adenylyl cyclase activity of membrane preparations by approximately 40%. This inhibition was reversed by atropine, occurred even in a Ca(2+)-free medium containing ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, and was not reproduced by the Ca2+ ionophore A23187. The carbachol effect was not prevented by simultaneous incubation of cells with either isobutylmethylxanthine, an inhibitor of phosphodiesterase, or H-7, an inhibitor of protein kinase. Pretreatment of cells with pertussis toxin to inactivate the Gi inhibitory protein also failed to affect the carbachol inhibition. Although carbachol did not reduce the basal or the TSH-stimulated cyclase activities when added to membranes directly during the assay, exposure of cells to carbachol for 2-4 hr resulted in long lasting inhibition of TSH-stimulated cyclase activity (for at least 24 hr); recovery was seen by 48 hr after its removal. Carbachol pretreatment had no effect on 125I-TSH binding to membranes but reduced the cyclase stimulation by not only TSH but also cholera toxin, guanosine 5'-O-(3 thio)triphosphate, and forskolin; it also significantly reduced the cholera toxin mediated AD[32P]-ribosylation of Gs in membranes. These data indicate that carbachol-induced inhibition of adenylyl cyclase occurs beyond the level of TSH receptor binding and that Gs is a possible site of its action. Thus, in dog thyroid cells, carbachol, via muscarinic receptors, can reduce the adenylyl cyclase activity by a process that does not involve Ca2+ or activation of phosphodiesterase. PMID- 1310142 TI - Molecular determinants of mu receptor recognition for the fentanyl class of compounds. AB - We report here a theoretical study of a series of fentanyl analogs with a wide range of affinities and selectivities at the mu receptor, designed to identify and characterize the molecular determinants of mu receptor recognition. In this work, a complete conformational search combining nested rotations and molecular dynamic simulations has been made, leading to identification of accessible conformers for all analogs and to the selection of a candidate bioactive form. In addition, electronic properties have been calculated and examined as possible modulators of recognition at the mu receptor. The results of these studies have led to a distinct pharmacophore for interaction at the mu receptor for this class of compounds, with the piperidine ring in a chair conformation and the N phenethyl and 4-phenylpropanamide substituents both equatorial. Moreover, four key moieties necessary for optimum receptor recognition and a postulated role for each of them in this recognition have been identified. These are (i) a protonated amine nitrogen, assumed to be involved in an initial electrostatic interaction with a negatively charged site on the receptor; (ii) a polar function capable of hydrogen-bonding with an electrophilic site; (iii) an aromatic ring involved in lipophilic interaction with a similar moiety; and (iv) a second aromatic ring, most probably involved in electron transfer interaction with the receptor. These requirements, taken together, form the basis of our proposed mechanism for mu receptor recognition. Not only is the presence of these components required for recognition, but specific steric relationships between them have been determined, implying the appropriate arrangement for interaction with complementary receptor sites. These steric parameters are pseudobond angles and one torsion angle that determine the relative spatial arrangement of these four moieties. They are the angles theta 1 and theta 3, defining the relative position of the protonated nitrogen and the polar function with each of the two aromatic rings, and the torsion angle eta 1, defining the orientation of the lone pair(s) on the polar proton-accepting function with respect to the lone pair on the piperidine nitrogen. This postulated mechanism of recognition provides a conceptual framework to understand why some compounds do and some do not recognize the mu receptor. PMID- 1310141 TI - Guanylnucleotide specificity for muscarinic receptor inhibitory coupling to cardiac adenylate cyclase. AB - The guanylnucleotide specificity of muscarinic acetylcholine receptor (MR) inhibitory coupling to cardiac adenylate cyclase (AC) was investigated under low MgCl2 (i.e., 0.5 mM) conditions. In purified cardiac sarcolemma, carbachol maximally inhibited AC activity 60% in the presence of GTP. Carbachol-dependent inhibition in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S) or guanylylimidodiphosphate [Gpp(NH)p] was of lesser magnitude (i.e., 30%) and was evident only during short incubation periods. Of greater interest, carbachol maximally inhibited AC activity in the presence of GDP and guanosine 5'-O-(2 thiodiphosphate (GDP beta S) by 35 and 60%, respectively. Control studies ruled out transphosphorylation of GDP and GDP beta S by nucleoside diphosphate kinase or guanylnucleoside triphosphate contamination as reasons for the inhibitory effects of GDP and GDP beta S. Furthermore, isoproterenol stimulated AC in the presence of GTP, GTP gamma S, and Gpp(NH)p but not in the presence of GDP or GDP beta S. Therefore, GDP and GDP beta S may serve as agonists on MR-activated Gi but not on beta-adrenergic receptor-activated Gs in these membranes. Time course studies revealed that carbachol-dependent inhibition of AC in the presence of either GTP or GDP occurred without a detectable lag period, and this inhibition was rapidly reversed by atropine. In contrast, a 1-2-min lag time was required for carbachol- and GDP beta S-dependent inhibition of AC to occur, and inhibition, once developed, was only partially and slowly reversed by atropine. Preincubation of sarcolemma with carbachol and GDP beta S, in the absence of ATP or under nonphosphorylating conditions, eliminated the lag time for inhibition of AC activity. Although it is unlikely that GDP and GDP beta S have physiological relevance of MR-Gi-AC coupling, these studies provide unique insights into this coupling mechanism in cardiac membranes. PMID- 1310143 TI - Intracellular metabolism of the antiherpes agent (S)-1-[3-hydroxy-2 (phosphonylmethoxy)propyl]cytosine. AB - (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is an antiviral phosphonate nucleotide analogue that displays activity against a range of herpesviruses. Anion exchange high performance liquid chromatography analysis of the 60% methanol extract from [14C]HPMPC-treated cells reveals the formation of three major metabolites. Two of these were identified as phosphorylated forms of HPMPC, HPMPC phosphate, and HPMPC diphosphate, by liberation of HPMPC upon acid digestion and coelution with synthetic standards on high performance liquid chromatography. The third metabolite, which is resistant to alkaline phosphatase cleavage but sensitive to phosphodiesterase, is proposed to be an HPMPC phosphate adduct. In herpes simplex virus-1-infected cells the same three metabolites are detected, at concentrations comparable to those in uninfected cells. When HPMPC is removed from the medium, the concentrations of the metabolites in cells decrease slowly, with half-lives of approximately 6, 17, and 48 hr for HPMPC phosphate, HPMPC diphosphate, and the HPMPC phosphate adduct, respectively. HPMPC diphosphate inhibits herpes simplex virus-1 and -2 DNA polymerases with a lower Ki than that for DNA polymerase alpha, and enzyme inhibition is competitive in each case. The formation and the persistence of HPMPC phosphates in cells and the selective inhibition of viral DNA polymerases by HPMPC diphosphate can explain why cells pretreated with HPMPC remain refractory to viral infection even long after HPMPC is removed from the medium. PMID- 1310144 TI - Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor. AB - Two isoforms of the human neurokinin-1 receptor were cloned and characterized in heterologous expression systems of mammalian cell culture and Xenopus oocytes. The two isoforms differ only in the length of the encoded polypeptide. The peptide-binding properties of the long form of human neurokinin-1 receptor are consistent with those of the native neurokinin-1 receptor of mammalian tissues, where substance P is the most potent agonist. Peptide agonists elicit an oscillating current in Xenopus oocytes expressing the long form. In contrast, the short form of human neurokinin-1 receptor expressed in COS cells binds substance P with an apparent affinity at least 10-fold lower than that of the long form, and it elicits the electrophysiological response only weakly in Xenopus oocytes. These data suggest that the short form couples to a different effector system. Sequence analysis suggested that the two isoforms may arise from alternative pre mRNA splicing. These results indicate that multiple forms of the human neurokinin 1 receptor exist and the differential activation of intracellular effector may be involved in generating the complex biological effects of substance P. PMID- 1310145 TI - Ion dependence of the partially purified mitochondrial dihydropyridine Ca2+ antagonist receptor. AB - The mitochondrial inner membrane contains specific binding sites for dihydropyridine (DHP) Ca2+ antagonists that are associated with an inner mitochondrial membrane anion channel (IMAC) [Mol. Pharmacol. 38:362-369 (1990)]. As in particulate preparations, binding of the DHP (+/-)-[3H]nitrendipine [( 3H]NTR) to partially purified mitochondrial DHP receptors strongly depended on a variety of cations and inorganic as well as organic anions. Monovalent anions saturably stimulated [3H]NTR binding with a potency rank order of I- greater than Br- greater than Cl- greater than F-. The potency rank order for monovalent cations was Cs+ greater than Rb+ greater than Li+ greater than K+ greater than Na+. [3H]NTR binding stimulation potency of the cations strikingly depended on their charge density, with EC50 values being 125 mM for K+, 5 mM for Ca2+, and 41 microM for La3+. This selectivity order clearly differed from one predicted on the basis of a simple surface charge-screening effect of the cations. In general, allosteric ion effects were due to changes in [3H]NTR affinity for the partially purified mitochondrial DHP receptor. SCN- and NO3-, known permeators of the IMAC [J. Biol. Chem. 262:15085-15093 (1987)], stimulated [3H]NTR binding with EC50 values of 26 mM and 96 mM, respectively. The IMAC permeators butylmalonate2- and 1,2,3-benzenetricarboxylate3- were ineffective when given alone but dose dependently inhibited 500 mM NaCl-stimulated [3H]NTR binding, as did PO4(1.5-) and SO4(2-). Gluconate-, which was reported not to permeate the IMAC, qualitatively behaved as a partial agonist with respect to Cl-. Glucuronate- was without effect on [3H]NTR binding to the partially purified mitochondrial DHP receptor. These results point to the existence of rather large ion-binding domains. The cation-binding site was estimated to have a minimum diameter of 0.67 nm. The anion-binding domain could accommodate either spherical ligands with diameters of up to 0.6 nm or molecules with a flat backbone with dimensions of approximately 0.9 nm x 0.7 nm x 0.3 nm. PMID- 1310146 TI - Nuclear binding of purified retinoblastoma gene product is determined by cell cycle-regulated phosphorylation. AB - The retinoblastoma tumor suppressor gene product (pRb) is a nuclear protein subject to cell cycle-regulated hyperphosphorylation. I constructed a recombinant vaccinia virus vector that expresses both the underphosphorylated and hyperphosphorylated forms of pRb and purified the recombinant protein by using immunoaffinity chromatography directed toward a synthetic carboxy-terminal epitope. To investigate the hypothesis that hyperphosphorylation of pRb is a means of controlling its growth-regulating activity, I tested purified pRb for the ability to be reincorporated into pRb-deficient nuclei in vitro. The underphosphorylated form of pRb efficiently reassociated with nuclei, but the hyperphosphorylated form remained soluble in this assay. Nuclear binding of pRb was enhanced by phosphatase treatment and reduced by phosphorylation of pRb effected by using a preparation of the cell cycle-regulatory kinase p34cdc2. Mutant-encoded proteins with altered E1A-binding domains failed to bind to nuclei. Pretreatment of target nuclei with nucleases and high-salt extraction did not alter the specificity of binding for underphosphorylated pRb. These observations demonstrate that hyperphosphorylation of pRb can regulate its interaction with nuclei, supporting the hypothesis that hyperphosphorylation controls the growth-regulatory activities of pRb. Further, at least one target of pRb binding appears to be an integral component of the nuclear envelope. PMID- 1310147 TI - Domain structure of U2 and U4/U6 small nuclear ribonucleoprotein particles from Trypanosoma brucei: identification of trans-spliceosomal specific RNA-protein interactions. AB - Maturation of mRNAs in trypanosomes involves trans splicing of the 5' end of the spliced leader RNA and the exons of polycistronic pre-mRNAs, requiring small nuclear ribonucleoproteins (snRNPs) as cofactors. We have mapped protein-binding sites in the U2 and U4/U6 snRNPs by a combination of RNase H protection analysis, native gel electrophoresis, and CsCl density gradient centrifugation. In the U2 snRNP, protein binding occurs primarily in the 3'-terminal domain; through U2 snRNP reconstitution and chemical modification-interference assays, we have identified discrete positions within stem-loop IV of Trypanosoma brucei U2 RNA that are essential for protein binding; significantly, some of these positions differ from the consensus sequence derived from cis-spliceosomal U2 RNAs. In the U4/U6 snRNP, the major protein-binding region is contained within the 3'-terminal half of U4 RNA. In sum, while the overall domain structure of the U2 and U4/U6 snRNPs is conserved between cis- and trans-splicing systems, our data suggest that there are also trans-spliceosomal specific determinants of RNA-protein binding. PMID- 1310148 TI - Transcriptional transactivation functions localized to the glucocorticoid receptor N terminus are necessary for steroid induction of lymphocyte apoptosis. AB - Genetic studies have suggested that transcriptional regulation of specific target genes (by either induction or repression) is the molecular basis of glucocorticoid-mediated lymphocyte apoptosis. To examine the role of transcriptional regulation more directly, we developed a complementation assay utilizing stable transfection of wild-type (wt) and mutant (nti) glucocorticoid receptor (GR) cDNA constructs into a GR-deficient S49 murine cell line (7r). Our data confirm that the level of functional GR is rate limiting for S49 apoptosis and moreover that the GR amino terminus (N terminus), which as been deleted from the nti GR, is absolutely required for complementation in this system. Surprisingly, we found that at physiological levels of receptor, expression of the nti GR in cells containing wt GR results in enhanced dexamethasone sensitivity rather than a dominant negative phenotype. One interpretation of these data is that DNA binding by wt-nti heterodimers may be functionally similar to that of wt-wt homodimers, indicating that GRE occupancy by at least one transactivation domain may be sufficient to induce the hormonal response. To determine whether acidic activating sequences such as those localized to the GR N terminus are important in the induction of lymphocyte apoptosis, we tested the activity of a chimeric receptor in which we replaced the entire GR N terminus with sequences from the herpes simplex virus VP16 protein. Our results demonstrate that 7r cells expressing VP-GR fusions are indeed steroid sensitive, strongly supporting the idea that S49 apoptosis is dependent on transcriptional regulation of specific genes which respond to acidic activating domains, implying that induction, rather than repression, may be the critical initiating event. PMID- 1310149 TI - Connections between RNA splicing and DNA intron mobility in yeast mitochondria: RNA maturase and DNA endonuclease switching experiments. AB - The intron-encoded proteins bI4 RNA maturase and aI4 DNA endonuclease can be faithfully expressed in yeast cytoplasm from engineered forms of their mitochondrial coding sequences. In this work we studied the relationships between these two activities associated with two homologous intron-encoded proteins: the bI4 RNA maturase encoded in the fourth intron of the cytochrome b gene and the aI4 DNA endonuclease (I-SceII) encoded in the fourth intron of the gene coding for the subunit I of cytochrome oxidase. Taking advantage of both the high recombinogenic properties of yeast and the similarities between the two genes, we constructed in vivo a family of hybrid genes carrying parts of both RNA maturase and DNA endonuclease coding sequences. The presence of a sequence coding for a mitochondrial targeting peptide upstream from these hybrid genes allowed us to study the properties of their translation products within the mitochondria in vivo. We thus could analyze the ability of the recombinant proteins to complement RNA maturase deficiencies in different strains. Many combinations of the two parental intronic sequences were found in the recombinants. Their structural and functional analysis revealed the following features. (i) The N-terminal half of the bI4 RNA maturase could be replaced in total by its equivalent from the aI4 DNA endonuclease without affecting the RNA maturase activity. In contrast, replacing the C-terminal half of the bI4 RNA maturase with its equivalent from the aI4 DNA endonuclease led to a very weak RNA maturase activity, indicating that this region is more differentiated and linked to the maturase activity. (ii) None of the hybrid proteins carrying an RNA maturase activity kept the DNA endonuclease activity, suggesting that the latter requires the integrity of the aI4 protein. These observations are interesting because the aI4 DNA endonuclease is known to promote the propagation, at the DNA level, of the aI4 intron, whereas the bI4 RNA maturase, which is required for the splicing of its coding intron, also controls the splicing process of the aI4 intron. We propose a scenario for the evolution of these intronic proteins that relies on a switch from DNA endonuclease to RNA maturase activity. PMID- 1310150 TI - In vitro phosphorylation of the erythropoietin receptor and an associated protein, pp130. AB - The cytoplasmic domain of the cloned erythropoietin (EPO) receptor (EPOR) contains no protein kinase motif, yet addition of EPO to EPO-responsive cells causes an increase in protein-tyrosine phosphorylation. Here we show that addition of EPO or interleukin-3 (IL-3) to an IL-3-dependent cell line expressing the wild-type EPOR causes a small fraction (less than 5%) of total cellular EPOR to shift in gel mobility from 66 to 72 kDa, due at least in part to phosphorylation. Using biotinylated EPO as an affinity reagent, we show that the 72-kDa species is greatly enriched on the cell surface. To demonstrate that a protein kinase activity associates with cell surface EPOR, cells were incubated with biotinylated EPO and then cross-linked with a thiol-cleavable chemical cross linker. The avidin-agarose-selected complexes were incubated with [gamma-32P]ATP. After in vitro phosphorylation and denaturation without reducing agent, both antiphosphotyrosine and anti-EPOR antibodies immunoprecipitated labeled 72-kDa EPOR and an unidentified 130-kDa phosphoprotein (pp130), indicating that a protein kinase is associated with cell surface EPOR and that a fraction of the EPOR was phosphorylated on tyrosine residues either in the cells or during the cell-free phosphorylation reaction. Under reducing conditions, the 72-kDa phosphorylated EPOR but not pp130 was immunoprecipitated with an anti-EPOR antibody, suggesting that the pp130 is bound to the EPOR by the thiol-cleavable chemical cross-linker. Previously, we showed that deletion of the 42 carboxy terminal amino acids of the EPOR allows cells to grow in 1/10 the normal EPO concentration, without affecting receptor number or affinity. Two carboxy terminal truncated EPO receptors that are hyperresponsive to EPO were poorly phosphorylated during the in vitro reaction, suggesting that the carboxy-terminal region of the EPOR contains a site for phosphorylation or a site for interaction with a protein kinase. Our data suggests that phosphorylation or interaction with a protein kinase in the carboxy-terminal region may down-modulate the proliferative action of the EPOR. PMID- 1310151 TI - Three novel functional variants of human U5 small nuclear RNA. AB - We have identified and characterized three new variants of U5 small nuclear RNA (snRNA) from HeLa cells, called U5D, U5E, and U5F. Each variant has a 2,2,7 trimethylguanosine cap and is packaged into an Sm-precipitable small nuclear ribonucleoprotein (snRNP) particle. All retain the evolutionarily invariant 9 base loop at the top of stem 1; however, numerous base changes relative to the abundant forms of U5 snRNA are present in other regions of the RNAs, including a loop that is part of the yeast U5 minimal domain required for viability and has been shown to bind a protein in HeLa extracts. U5E and U5F each constitute 7% of the total U5 population in HeLa cells and are slightly longer than the previously characterized human U5 (A, B, and C) species. U5D, which composes 5% of HeLa cell U5 snRNAs, is present in two forms: a full-length species, U5DL, and a shorter species, U5DS, which is truncated by 15 nucleotides at its 3' end and therefore resembles the short form of U5 (snR7S) in Saccharomyces cerevisiae. We have established conditions that allow specific detection of the individual U5 variants by either Northern blotting (RNA blotting) or primer extension; likewise, U5E and U5F can be specifically and completely degraded in splicing extracts by oligonucleotide-directed RNase H cleavage. All variant U5 snRNAs are assembled into functional particles, as indicated by their immunoprecipitability with anti-(U5) RNP antibodies, their incorporation into the U4/U5/U6 tri-snRNP complex, and their presence in affinity-purified spliceosomes. The higher abundance of these U5 variants in 293 cells compared with that in HeLa cells suggests possible roles in alternative splicing. PMID- 1310152 TI - Linked spontaneous CG----TA mutations at CpG sites in the gene for protein kinase regulatory subunit. AB - CG----TA transitions at CpG sequences account for many human point mutations and are thought to result from hydrolytic deamination of 5-methylcytosine residues in these sites. The gene for regulatory subunit of murine cyclic AMP-dependent protein kinase has two closely linked CpG sites, one of which is a strong hotspot for spontaneous CG----TA mutations leading to cyclic AMP resistance in S49 mouse lymphoma cells. About 5% of mutants with a spontaneous mutation at this CpG site had also acquired a second CG----TA mutation at the nearby CpG site. The two mutations were always at first positions of the Arg codons in which they occurred, and they were always together in a single regulatory subunit allele. Their linked appearance could be attributed to neither the selection conditions nor the preexistence of one mutation in the target cells. The high frequency of these double mutants suggests that their lesions result not from hydrolytic deamination but rather from an endogenous enzymatic mechanism. PMID- 1310153 TI - Characterization of a fusion cDNA (RARA/myl) transcribed from the t(15;17) translocation breakpoint in acute promyelocytic leukemia. AB - A nonrandom chromosomal translocation breakpoint, t(15;17)(q22;q21), is found in almost all patients with acute promyelocytic leukemia (APL). Most of these breakpoints occur within the second intron of the retinoic acid receptor-alpha (RARA) gene. We screened a cDNA library of APL and have identified and sequenced a cDNA transcribed from the t(15;17) translocation breakpoint. The 5' end of cDNA p1715 consists of 503 bp of the RARA exon II sequence. A 1.76-kb cDNA without homology to any known gene available in GenBank was found truncated downstream. This cDNA sequence was assigned to chromosome 15 by dot blot hybridization of the flow cytometry-sorted chromosomes. We designate this fusion cDNA RARA/myl, which is different from myl/RARA reported by de The et al. (H. de The, C. Chomienne, M. Lanotte, L. Degos, and A. Dejean, Nature (London) 347:558-561, 1990). This result demonstrates that the two different types of hybrid mRNA can be transcribed from this breakpoint. We screened a non-APL cDNA library and identified a 2.8-kb myl cDNA. This cDNA is able to encode a polypeptide with a molecular weight of 78,450. Alternative splicing of the myl gene which resulted in myl proteins with different C terminals was found. Southern blot analysis of the genomic DNA isolated from 17 APL patients by using the myl DNA probe demonstrated that the myl gene in 12 samples was rearranged. Northern (RNA) blot analysis of RARA gene expression in two APL RNA samples showed abnormal mRNA species of 4.2 and 3.2 kb in one patient and of 4.8 and 3.8 kb in another patient; these were in addition to the normal mRNA species of 3.7 and 2.7-kb. The myl DNA probe detected a 2.6-kb abnormal mRNA in addition to the normal mRNA species of 3.2, 4.2, and 5.5 kb. Using the polymerase chain reaction, we demonstrated that both RARA/myl and myl/RARA were coexpressed in samples from three different APL patients. From this study, we conclude that the t(15;17) translocation breakpoint results in the transcription of two different fusion transcripts which are expected to be translated into fusion proteins. PMID- 1310155 TI - Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia. PMID- 1310156 TI - Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia. PMID- 1310154 TI - Inhibitory effect of myristylation on transrepression by FBR (Gag-Fos) protein. AB - The myristylated v-fos product, FBR murine sarcoma virus (Gag-Fos) protein, exhibits a lower level of transrepression of the serum response element (SRE) than does c-fos protein (Fos). Mutation of the N-terminal myristylation site in FBR protein restored SRE transrepression. Replacement of N-terminal viral Gag sequences with the Fos N terminus also restored this activity, providing additional evidence that myristylation inhibits transrepression by FBR protein. However, the myristylated Gag domain did not inhibit SRE transrepression when fused to Fos, indicating that myristylation of a fos protein is not by itself sufficient to prevent SRE transrepression and that C-terminal mutation is necessary to inhibit transrepression by N myristylation. Comparison of transfection results with Fos C-terminal deletion mutants and the Fos/FBR chimeric mutant revealed that the FBR C terminus retained the potential for transrepression despite deletion of the normal Fos C terminus, whereas similar Fos deletion mutants did not. These results indicate that both N- and C-terminal mutations are required to inhibit transrepression by FBR protein and that multiple structural mutations accompanied by posttranslational protein modification alter gene regulation by FBR protein. PMID- 1310157 TI - Interindividual variability of central delay changes in the soleus H reflex pathway. AB - Central delay (CD) changes in the soleus H reflex pathway, as demonstrated by variations in the time interval between afferent (P1) and efferent (P2) neurographic volleys underlying the reflex response, were assessed in a group of normal subjects, both during the steady state and after homosynaptic spatial summation of afferent impulses. The maximal range of CD changes, regardless of whether "spontaneous" or provoked, showed significant interindividual differences whose size was positively related to the Hmax/Mmax ratio, provided that the extension of the subliminal fringe was suitably normalized. Comparatively similar variations in amplitude of the reflex motoneuronal discharge under different experimental conditions can be associated with different CD changes. Indeed, "spontaneous" CD fluctuations occurring during the steady state were consistently greater than CD reductions provoked by spatial summation, the gap size being negatively related to the Hmax/Mmax ratio. PMID- 1310158 TI - Invited review: autonomic dysfunction in peripheral nerve disease. AB - The autonomic nervous system is affected in most peripheral neuropathies, but only in a small number of conditions, such as diabetes, amyloidosis, Guillain Barre syndrome, porphyria, and familiar dysautonomia, is autonomic dysfunction of clinical importance. The pathological changes in the peripheral autonomic nervous system are similar to those in the peripheral somatic nerves. Autonomic disturbances are most likely to occur when there is acute demyelination or damage to small myelinated and unmyelinated fibers. Autonomic investigations should include tests of both sympathetic and parasympathetic function. Treatment consists of management of the underlying cause of peripheral neuropathy, physical and pharmacological measures. PMID- 1310159 TI - Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. AB - BACKGROUND: The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to streptozocin but less frequently causes vomiting. METHODS: In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: streptozocin plus fluorouracil, streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. RESULTS: Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also had a significant advantage in terms of survival (median, 2.2 vs. 1.4 years; P = 0.004) that was accentuated when we considered long-term survival (greater than 2 years). Chlorozotocin alone produced a 30 percent regression rate, with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil. Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent, and the responses were transient. Toxic reactions to all regimens included vomiting, which was least severe with chlorozotocin; hematologic depression; and, with long-term therapy, renal insufficiency. CONCLUSIONS: The combination of streptozocin and doxorubicin is superior to the current standard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil, but it produces fewer gastrointestinal side effects than the regimens containing streptozocin. It therefore merits study as a constituent of combination drug regimens. PMID- 1310161 TI - Progress against rare and not-so-rare cancers. PMID- 1310160 TI - Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. AB - BACKGROUND AND METHODS: Cisplatin (cis-diamminedichloroplatinum) has been reported to enhance the cell-killing effect of radiation, an effect whose intensity varies with the schedule of administration. We randomly assigned 331 patients with nonmetastatic inoperable non-small-cell lung cancer to one of three treatments: radiotherapy for two weeks (3 Gy given 10 times, in five fractions a week), followed by a three-week rest period and then radiotherapy for two more weeks (2.5 Gy given 10 times, five fractions a week); radiotherapy on the same schedule, combined with 30 mg of cisplatin per square meter of body-surface area, given on the first day of each treatment week; or radiotherapy on the same schedule, combined with 6 mg of cisplatin per square meter, given daily before radiotherapy. RESULTS: Survival was significantly improved in the radiotherapy daily-cisplatin group as compared with the radiotherapy group (P = 0.009): survival in the radiotherapy-daily-cisplatin group was 54 percent at one year, 26 percent at two years, and 16 percent at three years, as compared with 46 percent, 13 percent, and 2 percent, respectively, in the radiotherapy group. Survival in the radiotherapy-weekly-cisplatin group was intermediate (44 percent, 19 percent, and 13 percent) and not significantly different from survival in either of the other two groups. The survival benefit of daily combined treatment was due to improved control of local disease (P = 0.003). Survival without local recurrence was 59 percent at one year and 31 percent at two years in the radiotherapy-daily cisplatin group; 42 percent and 30 percent, respectively, in the radiotherapy weekly-cisplatin group; and 41 percent and 19 percent, respectively, in the radiotherapy group. Cisplatin induced nausea and vomiting in 86 percent of the patients given it weekly and in 78 percent of those given it daily; these effects were severe in 26 percent and 28 percent, respectively. CONCLUSIONS: Cisplatin, given daily in combination with the radiotherapy described here to patients with nonmetastatic but inoperable non-small-cell lung cancer, improved rates of survival and control of local disease at the price of substantial side effects. PMID- 1310162 TI - Popliteal-based filleted lower leg musculocutaneous free-flap coverage of a hemipelvectomy defect. AB - A 33-year-old man suffered from locally recurrent malignant fibrous histiocytoma of his left thigh unresponsive to previous excision, radiation therapy, chemotherapy, and hyperthermic treatment. He underwent radical hemipelvectomy for cure. Because of extensive tumor involvement, a free flap consisting of his distal left leg based on the popliteal artery was utilized to close the defect. Both the tibia and fibula were removed from their periosteal sheaths, and the foot was excised from the flap. The popliteal artery and vein were anastomosed to the iliac vessels. The flap survived, and the patient was discharged home after physical rehabilitation. We suggest that uninvolved portions of the distal leg may be utilized as a free flap to successfully close hemipelvectomy defects in selected patients when conventional pedicle flaps are unavailable. PMID- 1310163 TI - Carotid body tumors: US evaluation. AB - The ultrasound (US) findings in 20 patients with 23 carotid-body chemodectomas were reviewed. Twenty-two of 23 tumors could be seen at US; the remaining lesion could not be differentiated from surrounding enlarged lymph nodes resulting from thyroid cancer. The lesions were solid, slightly heterogeneous masses that ranged in size from 1.2 to 5.0 cm and were located within the carotid bifurcation. Pulsed Doppler analysis of blood flow within the tumor mass was possible in eight patients with nine chemodectomas, and low-resistance waveforms were obtained from multiple sites within the mass in all cases. The diagnostic possibility of a chemodectoma has to be considered when a solid mass is detected within the carotid bifurcation. On the basis of these findings, as US diagnosis was possible in 18 of 20 patients in the authors' series. Doppler analysis of the mass to evaluate intratumor blood flow is helpful in differentiating chemodectomas from other solid, nonhypervascular masses. PMID- 1310164 TI - Enhanced suppression of humoral immunity in DBA/2 mice following subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AB - Previous studies have indicated that mice which differ in their acute susceptibility to responses mediated by the Ah receptor have a pattern of suppression of the antibody response which is consistent with a role by the putative dioxin receptor. The objective of the present investigation was to compare the TCDD-induced suppression of the antibody response following acute and subchronic exposures in B6C3F1 mice, an Ah-high-responder strain, and DBA/2 mice, an Ah-low-responder strain. Results of our initial studies demonstrate that suppression of humoral immunity can be enhanced in DBA/2 mice approximately 10 fold following subchronic versus acute exposures to the same cumulative doses of TCDD. This change in suppression of the antibody response in DBA/2 mice was not accompanied by significant changes in liver weight (hepatomegaly), as was observed in the B6C3F1 strain when exposed under comparable conditions. In contrast, effects on thymus weight (involution) were enhanced in the DBA/2 mice following subchronic exposure and demonstrated a higher degree of atrophy than was seen in the B6C3F1 strain (68 versus 56% decrease in thymic weight at the 42 micrograms/kg cumulative dose). These findings suggest that multiple mechanisms may be operating to suppress humoral immunity in vivo and that the conditions of exposure can alter the toxic effects of TCDD in the DBA/2, Ah-low responsive, mouse strain. PMID- 1310165 TI - Comparative neuromuscular blocking actions of levamisole and pyrantel-type anthelmintics on rat and gastrointestinal nematode somatic muscle. AB - The basis for the comparative toxicity to parasitic nematodes and their mammalian hosts of the anthelmintics levamisole, pyrantel, and several related analogs on somatic nicotinic cholinergic transmission was examined. Measurements of muscle contractility and membrane potential were made using the isolated hemidiaphragm preparation of the rat and isolated axial muscle segments from the gastrointestinal nematode Haemonchus contortus. Pyrantel caused a dose- and time dependent reduction of nerve-evoked twitches in the rat diaphragm. These effects were exacerbated by increasing the frequency of phrenic nerve stimulation from 0.5 to 50 Hz. Levamisole was less potent and the onset of its effects slower than pyrantel. Neither drug significantly affected twitches evoked from d-tubocurarine blocked preparations following direct stimulation of the diaphragm. Twitch depression was reversed by washing, but not by application of physostigmine. In H. contortus, both drugs stimulated a spastic contraction and sustained paralysis in the concentration range of 1-10 microM, mimicking the action of nicotine. Neither nicotinic nor muscarinic antagonists blocked these responses. Moreover, neither nicotinic antagonists nor muscarinic agonists or antagonists had any independent effect on contractility of the parasite muscle segments. The blocking actions of levamisole and pyrantel on H. contortus axial muscle were associated with membrane depolarization at the muscle. In the rat-isolated hemidiaphragm, pyrantel, but not levamisole, depolarized end-plate regions of muscle fibers. d Tubocurarine blocked the depolarizing action of pyrantel but not levamisole on rat-isolated hemidiaphragm. In axial muscle fibers of H. contortus, d tubocurarine did not block the depolarizing actions of pyrantel, levamisole, or nicotine. 3-Bromo and 3-amino derivatives of levamisole were equipotent with and mimicked the actions of the parent compound on H. contortus axial muscle contractility. In the rat preparation, the 3-bromo derivative was more potent than levamisole or 3-amino-levamisole. 3-Amino-levamisole, but not 3-bromo levamisole, depolarized muscle end-plate membrane in the rat diaphragm. Results of the present study are consistent with the following conclusions: (a) both levamisole and pyrantel block contractility of nematode axial muscle by causing sustained depolarization of the muscle membrane; (b) both drugs block neuromuscular transmission at the mammalian neuromuscular junction but their mechanisms appear to differ; (c) levamisole and pyrantel are more potent blockers of neuromuscular transmission in H. contortus than in the rat. These results suggest that potentially important pharmacological differences exist between nematode and mammalian somatic nicotinic receptors. PMID- 1310166 TI - Structure-affinity relationships of retinoids with embryonic cellular retinoic acid-binding protein. AB - Separation and quantitation of cellular retinoic acid-binding protein (CRABP) in embryonic and fetal hamster tissues was accomplished with high-performance size exclusion chromatography. Binding affinity of 26 retinoids was established by in vitro displacement of high specific activity all-trans-[3H2]retinoic acid from fetal CRABP. The CRABP concentration in presomite-to-early somite (Day 8) hamster embryos was 1.9 pmol/mg cytosolic protein and increased to 7.5 pmol/mg protein in Day 13 fetuses; CRABP concentrations subsequently declined as gestation progressed. CRABP was located primarily in fetal brain and skin (5.8 +/- 0.3 and 2.2 +/- 0.1 pmol/mg protein, respectively), whereas only trace concentrations were found in fetal liver, placenta, and maternal uterus. Retinoids that could displace all-trans-retinoic acid from CRABP had a free acid at the polar terminus (or were carboxylate esters that were readily hydrolyzed to the corresponding free acid) and had a hydrophobic ring at the distal position. The ligand specificity of the CRABP studied here suggests that this protein was analogous to the CRABP I isoform. The in vitro binding affinities of teratogenic retinoids that competed for embryonic CRABP failed to correlate directly with relative teratogenic potency. In some instances, the latter observation can be related to extensive in vivo biotransformation of retinoids to multiple teratogenic metabolites and to retinoid persistence in the embryo. Three analogs containing a free carboxy terminus, SRI 5898-21, SRI 7323-78, and SRI 6153-40, were identified with high teratogenic potency but failed to bind fetal hamster CRABP. The structure-activity and binding data of the analogs studied here indicate that many, if not most, teratogenic retinoids (or their acidic metabolites) bind with embryonic/fetal CRABP, but the present data question the role for CRABP in their teratogenic mechanism of action. PMID- 1310167 TI - Deferoxamine inhibits methyl mercury-induced increases in reactive oxygen species formation in rat brain. AB - It has been suggested that methyl mercury may express its neurotoxicity by way of iron-mediated oxidative damage. Therefore, the effect of deferoxamine, a potent iron-chelator, on methyl mercury-induced increases in reactive oxygen species formation was studied in rat brain. The generation rate of reactive oxygen species was estimated in crude synaptosomal fractions using the probes 2',7' dichlorofluorescin diacetate and dihydrorhodamine 123. The formation rate of the fluorescent oxidation products was used as the measure of reactive oxygen species generation. Seven days after a single injection of methyl mercury (5 mg/kg, ip), the formation rate of reactive oxygen species was significantly increased in the cerebellum. Pretreatment with deferoxamine (500 mg/kg, ip) completely prevented the methyl mercury-induced increase in cerebellar reactive oxygen species generation rates. The oxidative consequences of in vitro exposure to methyl mercury (20 microM) were also inhibited by deferoxamine (100 microM). The formation of the iron-saturated complex ferrioxamine was not affected by a 10 fold excess of methylmercuric chloride or mercuric chloride, suggesting that a deferoxamine-mercurial complex does not form. The findings in this study: (1) provide evidence that iron-catalyzed oxygen radical-producing reactions play a role in methyl mercury neurotoxicity, (2) demonstrate the potential of fluorescent probes as a measure of reactive oxygen species formation, and (3) provide support for iron-chelator therapy in protection against xenobiotic induced oxidative damage. PMID- 1310168 TI - Spin trapping of free radical metabolites of carbon tetrachloride in vitro and in vivo: effect of acute ethanol administration. AB - A single dose of ethanol, when administered 18 hr prior to CCl4, potentiates the hepatotoxicity of the halocarbon. In these studies, spin trapping and electron spin resonance (ESR) spectroscopy methods were utilized to determine whether a single ethanol dose increased the metabolism of CCl4 to free radical intermediates. When hepatic microsomes from ethanol-treated or control rats were incubated with CCl4 and the spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN), the ESR signal of the trichloromethyl radical adduct of PBN was of similar intensity in both groups. The ethanol dose also failed to induce p-nitrophenol hydroxylase activity. When PBN and CCl4 were administered to rats, liver extracts contained ESR signals resulting primarily from the trichloromethyl radical adduct of PBN, and the signals were of similar intensity in both experimental groups. Higher concentrations of the carbon dioxide anion radical adduct of PBN were detected in plasma samples from ethanol-treated rats. However, when hepatocytes from ethanol-treated and control rats were incubated with PBN and CCl4, ESR signals of the carbon dioxide adduct were of similar intensity. These data suggest that the higher concentrations of the carbon dioxide adduct in the blood of ethanol-treated rats may be explained by early CCl4-induced damage to liver cell membranes, rather than increased rates of formation. The data in this report fail to support the hypothesis that a single dose of ethanol stimulates the hepatic metabolism of CCl4 to the trichloromethyl radical. Alternatively, ethanol may potentiate CCl4 toxicity by affecting some critical metabolic step subsequent to trichloromethyl radical formation. PMID- 1310169 TI - Acetaminophen-induced cytotoxicity in cultured mouse hepatocytes: effects of Ca(2+)-endonuclease, DNA repair, and glutathione depletion inhibitors on DNA fragmentation and cell death. AB - Hepatotoxic alkylation of mouse liver cells by acetaminophen is characterized by an early loss of ion regulation, accumulation of Ca2+ in the nucleus, and fragmentation of DNA in vitro and in vivo. Acetaminophen-induced DNA cleavage is accompanied by the formation of a "ladder" of DNA fragments characteristic of Ca(2+)-mediated endonuclease activation. These events unfold well in advance of cytotoxicity and the development of necrosis. The present study utilized cultured mouse hepatocytes and mechanistic probes to test whether DNA fragmentation and cell death might be related in a "cause-and-effect" manner. Cells were isolated by collagenase perfusion, cultured in Williams' E medium for 22-26 hr, and exposed to acetaminophen. Aurintricarboxylic acid, a general Ca(2+)-endonuclease inhibitor, and EGTA, a chelator of Ca2+ required for endonuclease activation, significantly decreased DNA fragmentation at 6 and 12 hr and virtually abolished cytotoxicity. N-Acetylcysteine also eliminated DNA fragmentation and cytotoxicity. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase stimulated DNA repair, failed to alter the amount of DNA fragmentation at 6 hr but substantially increased acetaminophen cytotoxicity in hepatocytes at 12 hr. With the exception of when DNA repair was inhibited by 3-aminobenzamide, Ca2+ accumulation in the nucleus, DNA fragmentation, and hepatocyte death varied consistently and predictably with one another. Collectively, these findings suggest that unrepaired damage to DNA contributes to acetaminophen-induced cell death in vivo and may play a role in necrosis in vivo. PMID- 1310170 TI - Differentiation of class I- and class II-directed donor-specific alloreactivity in bronchoalveolar lavage lymphocytes from lung transplant recipients. AB - Previous studies have demonstrated that donor antigen-specific primed-lymphocyte test (PLT) reactivity of bronchoalveolar lavage lymphocytes is strongly associated with acute pulmonary rejection and with obliterative bronchiolitis (OB); however, a systematic analysis of PLT reactivity as being class I-or II directed has not been performed. To assess reactivity directed against individual class I or II antigens, we tested a total of 67 BAL-derived lymphocyte samples from 26 recipients for alloreactivity in the PLT, using a pool of allogeneic cells and selected homozygous typing cells (HTCs) representing the HLA class I and II antigens expressed by the recipient and donor cells. The results obtained by PLT were correlated with the clinical status of the recipient with regard to rejection, infection, and OB. In 9 of 10 cases where transbronchial biopsy results were consistent with rejection, donor antigen-specific allogeneic PLT reactivity was observed and, more specifically, could be determined to be directed toward donor class II antigen in 8 of these cases. For 3 of 4 recipients tested chronologically, positive donor antigen-specific PLT reactivity was observed at the time of and 2-3 1/2 months prior to the diagnosis of rejection by transbronchial biopsy. During periods of acute infection, donor antigen-specific PLT reactivity was not observed; instead, non-specific PLT reactivity of BAL derived cells (i.e., reactivity that did not correlate with any defined HLA antigens) was observed as well as reactivity associated with the self-antigens expressed by the recipients' cells. The PLT reactivity of BAL-derived cells from a recipient diagnosed with OB correlated specifically with one of the disparate donor class I antigens (HLA-B44). In 23 cases, BAL cells were propagated in the presence of autologous cells and rIL-2, thereby allowing for sufficient numbers of cells to test with a panel of 29 HTCs and to analyze for cell surface phenotype. The cultured BAL cells from 4 recipients undergoing a rejection episode demonstrated a predominant CD4+ phenotype consistent with the class II directed reactivity observed in PLT. However, these results did not demonstrate a phenotype distinctive from the 7 BAL results obtained from 4 quiescent recipients. In marked contrast, the cultured BAL cells obtained from 4 recipients diagnosed with OB demonstrated a predominant CD8+ phenotype, with 60-92% of the cultured cells being CD8+. These results are consistent with the class I-directed reactivity observed in PLT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1310171 TI - The mechanism of cyclosporine's action in the inhibition of testosterone biosynthesis by rat Leydig cells in vitro. AB - We have previously demonstrated that cyclosporine inhibits testosterone (T) biosynthesis in vivo. To better understand the mechanism by which CsA inhibits T synthesis, interstitial cells were isolated from rat testes and incubated in the standard medium 199 with or without CsA (0-10 micrograms/ml) in the presence or absence of human chorionic gonadotropin (hCG, 10(-7) M) and 8-bromo cyclic AMP (cAMP, 0.5 mM) for 3 hr at 32 degrees C. The levels of cAMP and T were determined by RIA. CsA did not inhibit the basal secretion of T, but inhibited hCG stimulated T production in a dose-dependent manner (4 ng/10(6) cells vs. 10 ng/10(6) cells at a CsA dose of 5 micrograms/ml, P less than 0.05). Radioligand binding of 125I-hLH to testicular membranes was not affected by CsA, as CsA did not compete with hCG/LH for binding sites (25-28% binding with or without CsA). Similarly, the MIX-stimulated cAMP production was not affected by CsA (24.03 +/- 1.09 vs. 20.60 +/- 0.38 pmol/10(6) cells), suggesting that CsA does not inhibit the accumulation of the second messenger. However, when interstitial cells were incubated with CsA in the presence of cAMP, a significant dose-dependent decline in T secretion was observed (7 ng/10(6) cells vs. 20 ng/10(6) cells at a CsA dose of 5 micrograms/ml). To determine whether CsA inhibits the steps beyond cAMP stimulation of T secretion, the kinetic parameters (Km and Vmax) of steroidogenic enzymes, delta 4-3 keto-17 alpha hydroxylase (17 alpha-hydroxylase), and delta 4 3 keto-17 beta hydroxy steroid dehydrogenase (17B-HSD) were determined by using Michaelis Menten analysis. Results are shown in the presence of CsA vs. no CsA: Km and Vmax values for 17 alpha-hydroxylase were (2.32 vs. 7.98 microM) and (27.96 vs. 100.97 pmol/mg protein/min), respectively. For 17B-HSD the Km and Vmax were (2.14 vs. 1.52 microM) and (15 vs. 15 pmol/mg protein/min), respectively. These results indicate that CsA inhibits the activity of 17 alpha-hydroxylase uncompetitively and 17B-HSD activity competitively. In conclusion the primary site for CsA inhibition is the cAMP stimulation and, CsA inhibits T synthesis at multiple sites. PMID- 1310172 TI - Sodium lactate as an alternative to sodium bicarbonate in the management of metabolic acidosis after pancreas transplantation. PMID- 1310173 TI - Symptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipient treated with OKT3. AB - A prospective study to investigate risk factors for CMV disease was conducted in 94 renal transplant recipients. CMV disease was defined as either unexplained fever for greater than 3 days with viremia or unexplained fever for greater than 3 days with isolation of CMV from the urine or throat wash and at least one of the following: leukopenia, elevated serum alanine aminotransferase, or biopsy proved invasive tissue infection of the lung or gastrointestinal tract. Fifty three patients received immunosuppressive regimens consisting of prednisone and cyclosporine, with or without azathioprine. The remaining 41 patients were treated with these agents plus OKT3 (21 received OKT3 to treat rejection, 20 received OKT3 prophylactically). Thirty-seven patients were at minimal risk of CMV disease (donor and recipient seronegative for CMV); 12 patients were at risk of primary disease (donor seropositive, recipient seronegative), and 45 were at risk of reactivation disease (recipient seropositive at the time of transplantation). The incidences of CMV disease in the 3 groups were 0%, 58%, and 36%, respectively. Although the incidence of CMV disease in patients at risk of primary disease was not influenced by the immunosuppressive regimen, immunosuppression had a profound effect on the occurrence of CMV disease in CMV seropositive transplant recipients. The incidence of CMV disease in those receiving OKT3 was 59%; but only 21% in those who did not receive OKT3. OKT3 increased the risk of CMV disease five-fold (odds ratio 5.2 (95% confidence limits 1.4-17.5)). In the CMV-seropositive patient, OKT3 was also the most important predictor of CMV disease by multivariate analysis (P less than 0.002). A pilot study of preemptive therapy with ganciclovir (2.5 mg/kg daily during OKT3 therapy) in 17 patients decreased the incidence of CMV disease without appreciable toxicity. PMID- 1310174 TI - Cytomegalovirus infection of renal allografts. Detection by polymerase chain reaction. AB - Early laboratory diagnosis of acute cytomegalovirus infection in renal transplant recipients is desirable but often difficult. The polymerase chain reaction (PCR) technique for detecting CMV DNA, although it promises a high sensitivity, risks the possibility of detecting latent CMV infection and leading to false-positive results. To address this issue and the feasibility of applying PCR to renal biopsy specimens, we analyzed 37 renal allografts by PCR. Formalin-fixed or Bouin fixed paraffin-embedded materials were employed, and primers from the LA (late antigen) region of CMV were used. Amplified products were detected by gel electrophoresis and ethidium bromide staining, followed by Southern blot analysis. Of 21 nephrectomy samples, three showed CMV-specific amplified products by PCR, but CMV inclusion bodies were detected histologically in only one of the three. Of 16 renal biopsies, three specimens were positive by PCR, with rare viral inclusions histologically identified in only one. All PCR-positive patients had clinically significant CMV disease as evidenced by positive CMV culture and/or seroconversion. In contrast, all CMV-seropositive patients without active viral disease had PCR-negative allografts. We conclude that PCR positivity in the renal allograft strongly correlates with active CMV disease but not latent infection. For the diagnosis of active CMV disease in patients with a renal allograft, PCR provides a means that is more sensitive and objective than histologic examination, more specific than serology, and faster than viral culture. PMID- 1310175 TI - Identification and analysis of the gag-pol ribosomal frameshift site of feline immunodeficiency virus. AB - The pol genes of retroviruses are translated as gag-pol fusion proteins by ribosomal frameshifting within the gag-pol overlap region. During the ribosomal frameshift event, the gag open reading frame is shifted -1 nt to allow in-phase reading of the pol open reading frame. A consensus frameshift signal sequence of GGGAAAC within the gag-pol overlap region of feline immunodeficiency virus (FIV) has been identified followed by a sequence that has the potential for a pseudoknot tertiary structure. Using recombinant baculoviruses in which the frameshift occurs efficiently, the consensus sequence has been shown to be the site of the frameshift event. A mutation creating a termination codon just downstream of the putative frameshift signal sequence but upstream of the potential pseudoknot structure made a shorter gag product, but did not affect the efficiency of frameshifting. A mutation creating a termination codon just upstream of the putative frameshift signal made a shorter product and essentially abrogated frameshifting. Mutations in the first stem or the second stem in the potential pseudoknot structure severely reduced the frameshifting efficiency. Mutations which altered the length between the frameshift signal and the pseudoknot structure (the so-called spacer region) also reduced the frameshift efficiency. The insertion of a palindromic sequence, which could form a hairpin structure just upstream of the frameshift signal sequence, also affected the frameshifting. These results support the view that the ribosomal frameshift event in the FIV gag-pol region involves the identified signal sequence and appears to require the precisely positioned downstream sequence and indicated pseudoknot structure for efficient frameshifting. PMID- 1310176 TI - Persistent poliovirus infection: establishment and maintenance involve distinct mechanisms. AB - Mutants of poliovirus (PV) with highly modified biological properties can be selected in vitro in cells of neural origin. Mutations accumulate in the genome of type 1 PV strains selected in human neuroblastoma cells, modifying cell specificity and conferring to the virus the ability to persist in such nonneural cells as HEp-2c (Pelletier et al., Virology 180, 729 1991). With this cell system, we have both parent lytic strains and persistent PV mutants; these were used to study the mechanisms of the establishment and maintenance of the persistent infection. We found that a persistent infection was established when the lytic potential of the virus was reduced; this involved both an early and a late event of the virus cycle for the type 1 mutants. In contrast, maintenance of the infection did not correlate with the reduced lytic potential of the viruses, but rather with the selection of mutant cell populations of various phenotypes. Two cell lines, representative of two phenotypes, were studied in greater detail. In the first one, HEp-S32 (cl7), the PV receptor was not detected by cytofluorometry and viral genomes were detected by in situ hybridization in 2% of the cells. In the second cell line, HEp-S31 (cl18), 97% of the cells expressed the PV receptor, viral genomes were detected in 9-10% of the cells, and viral antigens in 5-10% of the cells. With this cell line, the cure of the culture or, alternatively, the lysis of the majority of cells, could be induced under specific culture conditions. We propose a model involving an equilibrium between an abortive and a lytic infection to explain the properties of cells persistently infected with PV. PMID- 1310177 TI - Metabolism of host and viral mRNAs in frog virus 3-infected cells. AB - Treatment of purified frog virus 3 (FV3) with nonionic detergent and high salt released an endoribonucleolytic activity and confirmed earlier findings of a virion-associated endonuclease. This observation, coupled with evidence implicating host and viral message destabilization in herpesvirus and poxvirus biogenesis, raised the question of what role, if any, mRNA degradation plays in FV3 replication. To answer this question, Northern analyses of mock- and virus infected cells were performed using probes for representative host and viral messages. These studies demonstrated that the steady state level of host messages progressively declined during the course of productive FV3 infection, whereas the steady state level of viral messages was not affected. To determine whether the decline in the steady state level of host mRNA was due to virus-induced degradation or to normal turnover coupled to virus-mediated transcriptional shut off, actin mRNA levels were examined in mock- and virus-infected cells in the presence and absence of actinomycin D. Under these conditions, actin mRNA levels declined more quickly in actinomycin D-treated, virus-infected cells, than in mock-infected cells incubated in the presence of actinomycin D suggesting that the decline in the steady state level of actin mRNA was due to degradation. However, although it appears as if host message degradation is responsible for virus-mediated translational shut-off, the ability of heat-inactivated FV3 to block cellular translation without destabilizing cellular messages indicates that message degradation is not required for translational inhibition. As noted above, the degradation of early FV3 messages was not involved in controlling the transition from early to late gene expression. Furthermore, the presence of abundant, but nontranslated, early messages late in infection, coupled with the inefficient translation of late messages in vitro supported earlier suggestions that FV3 gene expression is controlled, at least in part, at the translational level. Taken together, these results suggest that FV3 regulates gene expression in a unique manner and may be a good model to examine the mechanics of translational control. PMID- 1310178 TI - Molecular cloning and expression of the bacteriophage T7 0.7(protein kinase) gene. AB - The bacteriophage T7 0.7 gene encodes a protein which supports viral reproduction under specific suboptimal growth conditions. The 0.7 protein (gp0.7) shuts off host RNA polymerase-catalyzed transcription and also expresses a serine/threonine specific, cAMP-independent protein kinase (PK) activity. To determine the role of the gp0.7 PK in viral reproduction, the 0.7 gene of the T7(JS78) mutant phage- whose gp0.7 expresses only the PK activity--was cloned in the plasmid expression vector pET-11a. Cells containing the recombinant plasmid were viable, and upon IPTG induction produced a 30-kDa polypeptide, similar in size to the gp0.7 related polypeptide seen in T7(JS78)-infected cells. Extracts of cells containing this polypeptide can phosphorylate the exogenous substrate lysozyme. Expression of plasmid-encoded gp0.7(JS78) in vivo results in phosphorylation of the same proteins which are phosphorylated in T7(JS78)-infected cells; moreover, the plasmid-encoded gp0.7(JS78) is itself phosphorylated. The JS78 mutation changes Gln243 in gp0.7 to an amber codon, which explains the production of the truncated, 30-kDa gp0.7-related polypeptide, and implicates the 11-kDa C-terminal domain in host transcription shut-off. The T7(A23) 0.7 point mutant fails to express PK activity in infected cells. However, the truncated T7(A23)-related polypeptide, expressed from a plasmid, exhibits PK activity in vivo and in vitro, but with an altered specificity. Thus, the A23 mutation, which changes Asp100 to Asn, may identify a substrate recognition determinant. PMID- 1310179 TI - Analysis of cellular DNA synthesis during polyoma virus infection of mice: acute infection fails to induce cellular DNA synthesis. AB - It is widely believed that infection with various DNA viruses stimulates quiescent host cells to divide in preparation for virus replication. To examine this issue, the effects of acute polyoma virus infection on cellular DNA synthesis are observed in newborn mice. Using [3H]thymidine incorporation and fluorography of whole mouse sagittal sections, we observed clear, high-resolution images of organ-specific patterns of cellular DNA synthesis in newborn animals. No alteration in these patterns was observed during acute polyoma virus infection. Other methods, including measurements of [3H]thymidine-labeled DNA specific activities in various tissues and in situ autoradiography, also failed to detect virus-induced alterations in cellular DNA synthesis. These results indicate that newborn animals have high endogenous levels of DNA synthesis and imply that acute polyoma virus infection may not be associated with further induced levels of cellular DNA synthesis. PMID- 1310180 TI - Determination of the functional difference between human papillomavirus type 6 and 16 E7 proteins by their 30 N-terminal amino acid residues. AB - Human papillomavirus type 16 (HPV 16) is often found in cervical carcinomas, while HPV 6 is frequently associated with benign genital lesions. We have compared the abilities of the E7 transforming proteins of HPV 6 and 16 to transform various established and primary rodent cells by using the same heterologous promoter system. HPV 16 E7 efficiently induced anchorage-independent growth of all the rodent cell lines tested and immortalized or cooperated with ras in transforming primary rat cells. On the other hand, the transforming activity of HPV 6 E7 was lower and was restricted. By construction of chimeras of HPV 6 and 16 E7, we found that the difference in transforming activity between the two E7 proteins was mainly determined by the difference in their 30 N terminal amino acid residues, although some activities seem to be slightly affected by differences in their residual C-terminal portions. PMID- 1310181 TI - Analysis of immediate-early transcripts of equine cytomegalovirus. AB - Equine cytomegalovirus (ECMV) contains a linear, double-stranded DNA genome composed of a 146-kbp unique region flanked by a pair of 18-kbp direct repeat (DR) sequences at the termini. Cycloheximide, actinomycin D, and phosphonoacetic acid were applied to infected cell cultures to divide viral transcription into immediate-early (IE), early, and late phases. Eight IE transcripts were identified and mapped to two regions (I and II) of the viral genome. Two of these IE RNAs (13.0 and 5.5 kb in size) were transcribed from region I, which is located within the DR regions; these IE genes are diploid. The other IE transcripts (17.0, 9.0, 7.2, 6.8, 4.5, and 4.2 kb) originated from region II. IE region II is adjacent to region I and spans both unique and DR sequences at the left terminus of the genome. Region II IE transcripts are spliced and transcribed in the opposite direction from region I IE transcripts. IE transcripts from region I were present throughout the replication cycle, whereas those from region II were more abundant during the IE stage than at the early and late stages of infection. These studies demonstrate that ECMV differs from other herpesviruses in the organization and unusually large transcription units of its IE genes. PMID- 1310182 TI - Identification of 50- and 23-/25-kDa HeLa cell membrane glycoproteins involved in poliovirus infection: occurrence of poliovirus specific binding sites on susceptible and nonsusceptible cells. AB - Glycoproteins in the range 50 and 23/25 kDa were identified as poliovirus specific binding sites on HeLa cells with the monoclonal antibody mAb 122. mAb 122 is characterized by its partial inhibiting effect on poliovirus reproduction and adsorption when prebound to HeLa cells. The binding sites are endocytosed in native cells and specific for poliovirus as mAb 122 did not interfere with the adsorption of human rhinovirus type 14 (HRV 14). The poliovirus binding sites are present also on nonprimate so called nonsusceptible cells, e.g., mouse L-cells, as could be shown with sensitive ELISA based binding assays and performance of binding studies with fixed cells at 37 degrees. PMID- 1310183 TI - RNA editing in the phosphoprotein gene of the human parainfluenza virus type 3. AB - RNA editing of the human parainfluenza virus type 3 (HPIV3) phosphoprotein (P) gene was found to occur for the accession of an alternate discontinuous cistron. Editing occurred within a purine-rich sequence (AAUUAAAAAAGGGGG) found at the mRNA nucleotides 791-805. This sequence resembles an HPIV3 consensus transcription termination sequence and is located at the 5'-end of the putative D protein coding sequences. Editing at an alternate site (AAUUGGAAAGGAAAGG), mRNA nucleotides 1121-1136, for accession of a conserved V cistron, which is present in a number of paramyxovirus P genes, was not found to occur in HPIV3. In contrast with many other paramyxoviruses, editing was indiscriminate with the insertion of 1-12 additional G residues not present in the gene template. RNA editing was found to occur in both in vivo (HPIV3 infected cells) and in vitro (purified nucleocapsid complexes) synthesized mRNAs. Further, the in vitro prepared mRNA was edited regardless of whether the nucleocapsid complexes were transcribed in the presence or absence of uninfected human lung carcinoma (HLC) cell lysates. These results support the notion that RNA editing appears to be exclusively a function of viral proteins. PMID- 1310184 TI - Expression of bovine immunodeficiency-like virus envelope glycoproteins by a recombinant baculovirus in insect cells. AB - The bovine immunodeficiency-like virus (BIV) env open reading frame (ORF) contains both sequences encoding env and sequences for exon 1 of the putative rev gene. Recombinant baculoviruses incorporating BIV env ORF sequences were constructed to characterize the expression, processing, and immunogenicity of products of the BIV env ORF in insect cells and to develop reagents to study native BIV Env glycoproteins. A recombinant baculovirus containing the entire env ORF synthesized a nonglycosylated, 20-kDa, BIV-specific protein, apparently unrelated to native BIV Env proteins. In contrast, a recombinant baculovirus containing a truncated env ORF in which the coding sequences for rev exon 1 were deleted synthesized three size classes of glycosylated proteins in insect cells related to the BIV Env precursor (gp145), surface (gp100), and transmembrane (gp45) glycoproteins observed in BIV-infected mammalian cells. Oligomers of recombinant BIV Env proteins also formed in these baculovirus-infected insect cells. Immunofluorescence staining of intact insect cells infected by the baculovirus expressing BIV Env with BIV-specific serum demonstrated that the recombinant Env glycoproteins were expressed on the cell surface. Antisera raised to recombinant Env glycoproteins immunoprecipitated native gp145, gp100, and gp45 in BIV-infected bovine cells similar to sera from animals naturally or experimentally infected with BIV. PMID- 1310186 TI - In vitro characterization of the HSV-1 UL53 gene product. AB - The UL53 gene is the locus altered in many syncytial mutants of herpes simplex virus type 1 (HSV-1). However, the protein encoded by this gene has not been characterized. In this study, the UL53 protein was produced by in vitro translation of in vitro-transcribed UL53 RNA. Post-translational processing of the protein was studied by translation in the presence of pancreatic microsomal membranes. These microsomes carry out the processing steps that normally occur in the rough endoplasmic reticulum. The unprocessed protein had an apparent molecular weight of 27K, whereas the microsomally processed form had an apparent molecular weight of 36K. Two types of post-translational modification were detected: Addition of N-linked oligosaccharides and cleavage of an N-terminal signal sequence. N-linked glycosylation occurred in the first 112 residues of the protein, consistent with the presence of N-linked glycosylation signals at residues 48 and 58. Signal sequence cleavage occurred after residue 30. A membrane-binding, possibly transmembrane, domain was found between residues 113 and 170, probably consisting of the hydrophobic sequence 125-139. These results establish that the N-terminal domain of the UL53 protein, which is the site of those syncytial mutations that have been sequenced, is on the interior side of the microsomal membranes, which is topologically equivalent to the lumen of the rough endoplasmic reticulum and to the extracellular side of the plasma membrane. Additional hydrophobic, possibly transmembrane, domains exist nearer the C terminus of the protein. It also was found that the in vitro-translated UL53 protein aggregated when heated, even in the presence of SDS. This property was mapped to the C-terminal one-third of the protein. PMID- 1310185 TI - The simian varicella virus and varicella zoster virus genomes are similar in size and structure. AB - Simian varicella virus (SVV) DNA was purified from viral nucleocapsids and the molecular structure of the SVV genome was determined. SVV DNA was analyzed by agarose gel electrophoresis of BamHI, BglII, EcoRI, and PstI restriction endonuclease digests. SVV and varicella zoster virus (VZV) DNAs were demonstrated to have distinct restriction endonuclease profiles. Summation of the sizes of individual restriction endonuclease fragments indicate the size of SVV DNA is congruent to 121 kilobase pairs (kbp) or congruent to 76.8 megadaltons (Md). Electron microscopy, lambda exonuclease analysis, and Southern blot DNA hybridizations were utilized to determine the molecular structure of the SVV genome and to construct restriction endonuclease maps. The results indicate that SVV DNA consists of a long component (L, congruent to 100 kbp) covalently linked to a short component (S, congruent to 20 kbp) which is composed of a unique short sequence (Us, 5.3 +/- 0.7 kbp) bracketed by inverted repeat sequences (TRs and IRs, congruent to 7.2 kbp). The presence of 0.5 M PstI restriction endonuclease fragments indicates that the S component may invert relative to the L component and that the genome exists in two major isomeric forms. The findings demonstrate that the SVV and VZV genomes are similar in size and structure. PMID- 1310187 TI - Genomic organization and expression of simian foamy virus type 3 (SFV-3). AB - The complete nucleotide sequence of simian foamy virus type 3 (SFV-3) strain LK 3, isolated from an African green monkey, was determined. In addition to translation frames representing the gag, pol, and env genes, two open reading frames are located in the region between the env gene and the 3' long terminal repeat (LTR). Both SFV-3 and SFV-1 encode two open reading frames between env and the 3' LTR, whereas HFV encodes three open reading frames in this region. Northern blot analysis of cell cultures infected with SFV-3 revealed subgenomic RNAs for these open reading frames. The protease of SFV-3 is encoded by the pol gene in contrast to HFV which encodes the protease in the gag gene. Notably, the pol gene of SFV-3 in the +1 translational frame relative to the gag gene; this observation is in agreement with SFV-1, but differs for HFV and all other retrovirus genomes reported. Thus, gag-pol precursors of the SFVs appear to be expressed by a +1 frameshift. Nucleotide and deduced amino acid alignments of SFV 3, SFV-1, and HFV revealed an unexpected homology pattern; highest homologies are observed in the pol and env genes but low homologies are noted in the gag genes and the additional open reading frames. Analysis of phylogenetic trees confirms the classification of foamy viruses as a subfamily of retroviruses, distinct from the lentiviruses and oncoviruses. PMID- 1310189 TI - Differences in transforming activity and coded amino acid sequence among E6 genes of several papillomaviruses associated with epidermodysplasia verruciformis. AB - Using the polymerase chain reaction technique, we cloned and sequenced DNA fragments containing the E6 genes of the epidermodysplasia verruciformis (EV) associated HPVs 5, 8, 14, 20, 21, 25, and 47, of which only the sequences of HPVs 5, 8, and 47 have previously been reported. Based on the deduced amino acid sequence homology (57.3 to 83.0%), these HPVs could be divided into two clusters: HPVs 5, 8, and 47, and HPVs 14, 20, 21, and 25. The E6 genes of three HPVs from each cluster were examined for transforming activity toward a cultured rat fibroblast cell line, 3Y1, using the retrovirus-mediated gene transfer technique, and all were found to induce morphological transformation. However, the E6 genes of the first cluster were more potent than those of the second. Since HPVs 5 and 8 are the most frequently found HPVs in malignant lesions of EV patients, the observed in vitro transforming activities of the E6 genes may reflect their oncogenic potential in humans. PMID- 1310188 TI - Hepatitis A virus polyprotein synthesis initiates from two alternative AUG codons. AB - The genomic RNA of hepatitis A virus has two potential translation initiation sites for synthesis of a 251-kDa polyprotein. It is not known which of these AUG codons, located at positions 735-737 and 741-743, is used in vitro or in vivo. Site-directed mutagenesis was carried out to eliminate each start codon independently. Transcripts from the unmodified and modified cDNA clones were used either to program an in vitro translation system or for transfection of BS-C-1 cells. In vitro and in vivo translation data revealed preferential usage of the downstream AUG located at position 741 to 743, although either site could be utilized in the absence of the other. Both modified RNAs were able to induce productive infections in BS-C-1 cells. Deletion of almost all of the 5' untranslated region (5'UTR) of the RNA, however, stimulated selection of AUG 735 737 in vitro resulting in equal utilization of both sites, suggesting a strong influence of the 5'UTR for directing the ribosome to a specific internal initiation site. PMID- 1310190 TI - A spleen necrosis virus-based retroviral vector which expresses two genes from a dicistronic mRNA. AB - We have investigated a novel strategy for coexpressing two genes from a retroviral vector. The 5' nontranslated leader region of at least some picornavirus RNAs contains a sequence that can act as an internal ribosome entry site allowing initiation of translation at a downstream AUG codon in a 5' cap independent manner. To investigate whether such a sequence can function in the context of a retroviral vector, we constructed a spleen necrosis virus-based vector carrying two selectable marker genes separated by the leader region of encephalomyocarditis virus. This vector was genetically stable and efficiently expressed both markers from a single dicistronic transcript. Since the expression of two genes by other strategies in retroviral vectors can often be problematic, these results offer a promising new approach for the design of "double gene" retroviral vectors. PMID- 1310191 TI - The 9-kDa hydrophobic protein encoded at the 3' end of the porcine transmissible gastroenteritis coronavirus genome is membrane-associated. AB - The open reading frame potentially encoding a 78 amino acid, 9101 Da hydrophobic protein (HP) and, mapping at the 3' end of the porcine transmissible gastroenteritis coronavirus (TGEV) genome, was shown to be expressed during virus replication. The cloned HP gene was placed in a plasmid under control of the T7 RNA polymerase promoter and in vitro translation of transcripts generated in vitro yielded a 9.1-kDa protein that was immunoprecipitable with porcine hyperimmune anti-TGEV serum. Antiserum raised in rabbits against a 31 amino acid synthetic polypeptide that represented the central hydrophilic region of HP specifically immunoprecipitated HP from TGEV-infected cells. HP was further shown to become associated with microsomal membranes during synthesis in vitro and was found to be closely associated with the endoplasmic reticulum and cell surface membranes in infected cells. The intracellular location of HP suggests that it may play a role in the membrane association of replication complexes or in virion assembly. PMID- 1310192 TI - Sequences of the four larger proteins of a porcine group C rotavirus and comparison with the equivalent group A rotavirus proteins. AB - The sequences of the four larger proteins of rotavirus group C (Cowden strain) are presented and compared with the sequences of the corresponding group A proteins. They exhibit a significant level of homology, allowing gene coding assignment for the group C rotavirus. The coding strategy of the group C virus RNA segment is the same as that for the group A large segments as one long open reading frame is present in each segment. The genome segment 1 encodes the structural protein VP1 which presents the RNA-dependent RNA polymerase consensus motifs. The VP1 protein is the most highly conserved between the rotaviruses of groups A and C. The genome segment 2 encodes the VP2 protein. The deduced protein sequence does not present the putative leucine zippers identified in the group A protein but its amino terminal is hydrophilic and highly charged as previously noted for the group A protein. The genome segment 3 encodes for a protein homologous to the group A outer capsid protein VP4. As observed among the various group A sequences, the amino terminal is the region presenting the fewest similarities. A cleavage region and a putative fusion motif similar to those present in the group A viruses have been identified. For this protein the comparison has been extended to the IDIRV [corrected] VP3 previously sequenced and indicates that groups A and C VP4 proteins are much more related to each other than to the group B equivalent. The genome segment 4 encodes for a protein showing an approximate 40% sequence identity to the minor core protein, VP3, of the group A rotavirus. This remarkable conservation of primary structures argues for severe functional constraint on the evolution of these proteins. PMID- 1310193 TI - Characterization of the roles of conserved cysteine and histidine residues in poliovirus 2A protease. AB - The primary processing of the poliovirus polyprotein is catalyzed by 2A protease (2Apro) which cleaves at the 1D/2A junction in a very rapid cotranslational reaction. In addition, 2Apro also indirectly induces cleavage of the p220 component of eIF-4F, which results in selective inhibition of host protein synthesis. Earlier studies have indicated that 2Apro is related to 3C protease (3Cpro) and is structurally similar to trypsin-like serine proteases with the substitution of Cys109 as the nucleophile. We noticed that 2Apro of enteroviruses and rhinoviruses contains a specific motif of Cys55-Xaa-Cys57-Xaan-Cys115-Xaa His117 which is absolutely conserved, but which is not found in viral 3Cpro or known cellular serine proteases. To better understand the specific roles these conserved cysteine and histidine residues played in the structure/function of 2Apro, we constructed a series of 2Apro mutants by site-specific mutagenesis and analyzed the mutant enzymes with respect to their biochemical properties. Conservative amino acid replacements at Cys55, Cys57, Cys115, or His117 resulted, in each case, in a complete loss of both in cis and in trans activities of 2Apro. To determine the function of these residues, we examined the biochemical/structural features of 2Apro expressed in a cell-free rabbit reticulocyte lysate system. Gel mobility shift and chemical modification data suggest that these cysteine residues do not form intra-molecular disulfide linkages as a structural feature of 2Apro. However, studies with metal chelators did not eliminate the possibility that 2Apro contains a metal-binding ligand. Finally, our results suggest that these conserved cysteine and histidine residues, including Cys55, Cys57, Cys115, and His117, are critical in maintaining the active conformation of 2Apro structure and essential in supporting the catalytic activity of 2Apro. PMID- 1310194 TI - Persistence of archetypal JC virus DNA in normal renal tissue derived from tumor bearing patients. AB - JC virus DNAs derived from the urine of nonimmunosuppressed individuals generally contain an archetypal regulatory region which may have generated various regulatory regions of JC virus from from the brain with progressive multifocal leukoencephalopathy (PML). In this study, we examined whether JC virus persisting in normal human kidney tissue contains the archetypal regulatory region. Renal medulla, cortex, and tumor from 32 patients bearing renal tumors were screened for JC virus DNA by blot hybridization. Viral DNA was detected in the medulla in 13 cases (41%), in the cortex in 2 cases (6%), but not at all from the tumor. A number of viral DNA-positive specimens (8 from the medulla and 2 from the cortex) were used to amplify and sequence viral regulatory regions by polymerase chain reaction. Structures of the regulatory regions from all the specimens were, with a few nucleotide variations, identical with that of the archetypal region which was previously detected in the JC virus DNA from urine. This finding supports the hypothesis that the JC virus associated with PML evolved from the archetypal JC virus during persistence in human hosts. Furthermore, we present evidence that renal JCV is replicating and that progeny virions are excreted into the urine. PMID- 1310195 TI - Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity. AB - Mouse hepatitis virus (MHV), a coronavirus, causes encephalitis and demyelination in susceptible rodents. Previous investigations have shown that the MHV spike (S) protein is a critical determinant of viral tropism and pathogenicity in mice and rats. To understand the molecular basis of MHV neuropathogenesis, we studied the spike protein gene sequences of several neutralization-resistant variants of the JHM strain of MHV, which were selected with monoclonal antibodies (MAbs) specific for the S protein. We found that variant 2.2-V-1, which was selected with MAb J.2.2 and primarily caused demyelination, had a single point mutation at nucleotide (NT) 3340, as compared to the parental JHM virus, which predominantly caused encephalitis. This site was in the S2 subunit of the S protein. In contrast, variant 7.2-V-1, which was selected with MAb J.7.2 and primarily caused encephalitis, had two point mutations at NT 1766 and 1950, which were in the S1 subunit. Finally, the double mutant 2.2/7.2-V-2, which was selected with both MAbs J.2.2 and J.7.2, and was attenuated with respect to both virulence and the ability to cause demyelination, had a deletion spanning from NT 1523 to 1624 in the S1 and a point mutation at NT 3340 in the S2. We conclude that at least two regions of the S protein contribute to neuropathogenicity of MHV. We have also isolated a partial revertant of 2.2-V-1, which was partially resistant to MAb J.2.2 but retained the same neuropathogenicity as the variant 2.2-V-1. This revertant retained the mutation at NT 3340, but had a second-site mutation at NT 1994, further confirming that NT 3340 contributed to the pathogenic phenotype of MHV. By comparing these results with MHV variants isolated in other laboratories, which had mutations in other sites on the S gene and yet retained the demyelinating ability, we suggest that the ability of JHM viruses to induce demyelination is determined by the interaction of multiple sites on the S gene, rather than the characteristics of a single, unique site. Our study also revealed the possible presence of microheterogeneity of S gene sequence, particularly in the S1 region, in these viruses. The sequence microheterogeneity may also contribute to the differences in their biological properties. PMID- 1310196 TI - Molecular and biological characterization of cottontail rabbit papillomavirus variant DNA sequences integrated in the VX7 carcinoma. AB - The transplantable VX7 carcinoma was derived from a tumor induced by a recoverable strain of cottontail rabbit papillomavirus (CRPV) able to replicate in domestic rabbits. Low levels of late viral gene expression have been retained through serial propagation in rabbits. We have cloned and characterized the three major types of CRPV sequences integrated in this tumor, a genome-length 8-kb DNA molecule and two rearranged 9- and 3.8-kb molecules. The VX7 8-kb DNA displays only a few differences in its restriction map, when compared to the wild-type (wt) CRPV DNA. The VX7 9- and 3.8-kb DNAs derive from the VX7 8-kb DNA since they share the same restriction site polymorphism. The VX7 9-kb DNA contains a duplication of the E6 open reading frame. The VX7 3.8-kb DNA results from the deletion of most of the E region and the insertion, between the borders of the deletion, of 174-nucleotide-long segment of the long control region potentially driving the expression of a truncated L2 protein. Both VX7 9- and 3.8-kb species potentially allow the expression of abnormal E6 fusion proteins. Nineteen point mutations were detected in the 3.8-kb DNA, compared to the wt CRPV DNA. None of these molecules were able to induce warts in domestic rabbits, in contrast to wt CRPV DNA. Furthermore, when cloned VX7 DNAs were inoculated together with wt CRPV DNA, none of the VX7 CRPV sequences, as identifiable by their specific restriction enzyme cleavage patterns, could be detected in the resulting warts. This suggests that CRPV sequences integrated in the VX7 carcinoma are no longer able to replicate as episomes, which might be a prerequisite for the production of warts. PMID- 1310197 TI - Differential response of human interferon-beta promoter elements to trans activation by HSV VP16 and IRF-1. AB - The trans-activation potential of herpes simplex virus (HSV) VP16, either alone or in combination with interferon regulatory factor 1 (IRF-1), was examined using hybrid promoters containing different regulatory elements from the interferon beta promoter. Coexpression of HSV VP16 and IRF-1 differentially activated the AAGTGA hexamer construct Th(2), the AAAGGA hexamer Thm(2) construct, and the natural IFN-beta promoter. Surprisingly, high concentrations of IRF-1 inhibited expression of the PRDII containing reporter P2(1)/CAT. These results indicate that trans-activation by HSV VP16, acting through distinct cellular transcription factors, may be involved in stimulation of IFN-beta regulatory domains. PMID- 1310198 TI - The phylogenetic relationship and complete nucleotide sequence of human papillomavirus type 35. AB - The 7851-bp nucleotide sequence of human papillomavirus (HPV) type 35 was determined. HPV 35 is associated with high-grade cervical intraepithelial neoplasia and invasive carcinomas. From the HPV 35 sequence, open reading frames encoding putative proteins E6, E7, E1, E2, E4, E5, L2, and L1, common to other mucosal HPV types, were identified. Structural and control elements present in the long control region (LCR) conserved among other mucosal HPV types were also present in HPV 35. Analysis of the LCR revealed an additional 20-bp sequence element present in all HPV types associated with malignant proliferation. To further classify HPV 35 with regard to oncogenic potential, phylogenetic analysis of the E6 and E7 proteins from the anogenital HPV types 6, 11, 16, 18, 31, 33, 35, 39, 43, 44, 45, and 51 was performed. This analysis indicated three distinct HPV subgroups; those associated with benign lesions and two branches of those HPV types more often associated with malignant proliferation. HPV 35 is most closely related to HPV types 31 and 16. PMID- 1310199 TI - Transactivation of the HIV-1 LTR by HSV-1 immediate-early genes. AB - Herpes simplex virus type 1 (HSV-1) activates transcription from the long terminal repeat (LTR) promoter region of the human immunodeficiency virus type 1 (HIV-1). HSV-1 immediate-early (IE) genes ICP0 and ICP4 are thought to be important mediators of this process, which is known to involve the induction of the cellular activators NF-kappa B and Sp1. We demonstrate that ICP0 and ICP4 transactivation of the LTR is largely dependent on the presence of NF-kappa B and Sp1 binding sites. However, in Jurkat CD4-positive lymphocytes, HSV-1 activates LTR constructs lacking all NF-kappa B or Sp1 Binding sequences. This effect is still evident when all sequences upstream of the TATA motif are removed. Such enhancer-independent transactivation can be produced by cotransfection of ICP0 and ICP4. Thus HSV-1 IE genes transactivate the HIV-1 LTR both through the induction of NF-kappa B and Sp1 and through another as yet undefined cellular factor. PMID- 1310200 TI - Oxytocin given in a pulsatile manner to the ewe at 120 to 140 days' gestational age increases fetal sheep plasma cortisol. AB - A single intravenous injection of oxytocin into pregnant sheep (123 to 144 days' gestational age) causes a bout of myometrial activity and an increase in fetal plasma corticotropin levels. We hypothesized that a sustained increased frequency of myometrial contractures accelerates the normal increase in fetal adrenal secretion in sheep in the last 3 weeks of gestation. To test this hypothesis, pulses of saline solution (group 1, 9 ewes and 10 fetuses) or oxytocin (group 2, 11 ewes and 12 fetuses) 600 or 960 microU/kg/min for 5 of every 30 minutes were infused into the maternal jugular vein for 6 days beginning at day 128 +/- 2 (mean +/- SD) days' gestational age. Total myometrial activity increased to 160% of baseline in group 2 by day 6. Myometrial activity did not change throughout the study in group 1. Maternal plasma cortisol concentrations did not rise during oxytocin infusion when compared with their own baselines (group 2) and were not different from concentrations in saline-infused ewes (group 1). By day 4 of oxytocin administration fetal plasma cortisol concentrations had risen significantly above baseline in group 2 (p less than 0.05). Fetal plasma cortisol concentrations did not rise in group 1. Corticotropin levels were not elevated in the fetal carotid arterial plasma of either group. A small but significant decrease occurred in fetal carotid arterial PO2 in group 2 by day 6 but not in group 1. In conclusion, increased myometrial activity produced by pulsed oxytocin is accompanied by increased fetal plasma cortisol concentrations, demonstrating that long-term alteration of myometrial activity affects fetal adrenal function over several days at this critical period of gestation. PMID- 1310201 TI - Possible transplacental transmission of human papillomaviruses. AB - OBJECTIVE: The objective of this study was to examine the possibility of intrauterine human papillomavirus infection of fetuses by transplacental transmission of human papillomavirus before delivery. STUDY DESIGN: Specimens of cervicovaginal cells and peripheral blood mononuclear cells were obtained from 52 consecutive pregnant women in the third trimester of pregnancy. Cord blood specimens were also obtained from the neonates born to these mothers. Presence of human papillomavirus types 16 and 18 deoxyribonucleic acid was analyzed by an in vitro enzymatic deoxyribonucleic acid amplification method. RESULTS: Human papillomavirus type 16 deoxyribonucleic acid was found in 6 (11.5%) cervicovaginal and in 9 (17.3%) peripheral blood mononuclear cell specimens. Seven cord blood specimens from neonates born to mothers who were positive for peripheral blood mononuclear cell human papillomavirus type 16 deoxyribonucleic acid were found to contain human papillomavirus type 16 deoxyribonucleic acid. One cervicovaginal and two peripheral blood mononuclear cell specimens contained human papillomavirus type 18 deoxyribonucleic acid, but none of the cord blood specimens contained human papillomavirus type 18 deoxyribonucleic acid. CONCLUSION: These results seem to suggest possible transplacental transmission of the virus and the potential association of such transmission with the status of human papillomavirus in peripheral blood mononuclear cells. PMID- 1310202 TI - Insulin-like growth factor I and II binding in human myometrium and leiomyomas. AB - OBJECTIVES: The purpose of this study is to determine if the human myometrium has receptors for insulin-like growth factors I and II and whether the concentration of these receptors is increased in leiomyomas. STUDY DESIGN: Specific binding of iodine 125-labeled insulin-like growth factor I and II was examined in the membrane preparations of myometrium and leiomyomas obtained from 10 women with uterine leiomyomas. RESULTS: Binding studies indicate presence of specific binding sites for both insulin-like growth factors I and II in the myometrium and leiomyoma. The concentration of binding sites for insulin-like growth factor I, but not for insulin-like growth factor II, was significantly (p less than 0.01) higher in leiomyomas than in the myometrium. The dissociation constants for insulin-like growth factors I and II receptors in both myometrium and leiomyoma were similar. CONCLUSION: insulin-like growth factor I, but not insulin-like growth factor II, receptors are increased in leiomyomas compared with those in myometrium, indicating that insulin-like growth factor I may play a role in the generation and/or growth of this tumor. PMID- 1310203 TI - Prenatal diagnosis of fetal cytomegalovirus infection. AB - A prospective study (1988 to 1990) to evaluate the risk of fetal cytomegalovirus transmission was conducted with 1771 pregnant women; the test results of 861 were seronegative (48.6%). At each prenatal visit they were tested for serologic data and cytomegalovirus excretion in urine, saliva, and cervical secretions. If seroconversion occurred (with or without cytomegalovirus excretion), ultrasonography, amniocentesis, and cordocentesis were performed at 22 weeks' gestation; 7 cases of primary cytomegalovirus infection were investigated. In 5 cases the amniotic fluid cultures were positive; in 3 cases the fetal blood test results were positive for specific immunoglobulin M; and in 2 cases brain ultrasonography results were positive. Infection was confirmed with biopsies of fetal tissue. In two other cases, the cord blood and amniotic fluid test results were negative, and the neonates were free of infection. PMID- 1310204 TI - Role of calcium and cAMP messenger systems in intracellular pH regulation of osteoblastic cells. AB - We have recently shown that two mechanisms are involved in the regulation of pHi in the osteoblastic phenotype cell line UMR-106 (Na(+)-H+ antiporter and a Na(+) independent Cl(-)-HCO 3(-)-OH- exchanger). In the present work, we used the pH sensitive dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein as well as isotope fluxes to investigate the influence of second messengers on the activity of these transporters. Elevation in intracellular calcium concentration [( Ca2+]in) in UMR 106 cells (measured by fura-2 fluorescence) is followed by stimulation of the Cl( )-HCO3- exchanger, leading to cytosolic acidification. Subsequently, cell alkalinization, mediated by the Na(+)-H+ exchanger, restores pHi to its resting value. An acute reduction in [Ca2+]in abruptly stops the activity of the anion exchanger while having no influence on the activity of the Na(+)-H+ exchanger. The stimulatory effect of Ca2+in on the anion exchanger is dose dependent and is abrogated by the calmodulin inhibitors N-(6-aminohexyl)-5-chloro naphthalenesulfonamide and calmidazolium. An increase in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) brought about by forskolin, 8-bromo-cAMP, or prostaglandin E2 leads to inhibition of activity of both the Na(+)-H+ antiporter and the anion exchanger. The suppressive effect of cAMP on Cl(-)-HCO3- exchange could be overcome by elevating [Ca2+]in. We conclude that 1) Ca2+in and cAMP can influence pHi in osteoblasts by altering the activities of pHi regulatory mechanisms and 2) the effect of Ca2+in is probably mediated by calmodulin. PMID- 1310205 TI - Synergism between cAMP and ATP in signal transduction in cardiac myocytes. AB - ATP transiently increases the intracellular Ca2+ concentration in cardiac myocyte suspensions. Pretreatment with norepinephrine (NE) greatly potentiates the ATP response. We performed experiments on adult rat myocyte suspensions loaded with fura-2 to investigate the mechanism of NE potentiation. We found that forskolin (an activator of adenylate cyclase), 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase), and permeative adenosine 3',5'-cyclic monophosphate (cAMP) analogues potentiate the increase in cytosolic Ca2+ concentration induced by ATP. NE, forskolin, and 8-(4-chlorophenylthio)-cAMP all increase Vmax of the Ca2+ response curve of ATP. Measurement of cAMP by radioimmunoassay confirmed that the changes in the ATP response were accompanied by an increase in cAMP. These results suggest that the noradrenergic potentiation of the ATP-induced Ca2+ mobilization involves cAMP as a second messenger. Patch-clamp studies of isolated myocytes showed that neither NE nor forskolin alters the inward current elicited by ATP, but rather they increase the duration of secondary slow action potentials elicited by ATP. NE also increases the Ca2+ current through L-type Ca2+ channels in the myocytes. We conclude that NE potentiates the ATP-induced Ca2+ transient by increasing cAMP levels and that one of the early events is the increase of the inward Ca2+ current during the action potential. PMID- 1310206 TI - Identification of a membrane protein from T84 cells using antibodies made against a DIDS-binding peptide. AB - The outwardly rectified chloride channel of secretory epithelial cells is inhibited by disulfonic stilbene (DS) compounds such as 4,4'-diisothiostilbene 2,2'-disulfonic acid (DIDS) [R. J. Bridges, R. T. Worrell, R. A. Frizzell, and D. J. Benos, Am. J. Physiol. 256 (Cell Physiol. 25): C902-C912, 1989]. A 13-amino acid peptide (P49) corresponding to the putative DS binding site region of the murine anion exchange protein was synthesized, and polyclonal antibodies were generated against it and then purified over a P49 affinity column. The resulting monospecific antibodies reacted on Western blots with a 95- to 100-kDa protein from human erythrocytes and a 55- to 60-kDa protein from the human colonic tumor cell line, T84. The reaction with T84 protein did not appear to represent recognition of an anion exchanger because anion efflux from T84 cells was independent of external Cl-. In addition, monoclonal antibodies raised against human band 3 recognized the band 3 protein in human red cell ghost preparations but recognized nothing in T84 cell membrane preparations. In T84 cells, DIDS protected the 60-kDa protein from antibody binding. The anti-P49 antibody blocked outwardly rectified Cl- channels incorporated into planar lipid bilayer membranes from rat colon. Immunocytochemical data reveal specific binding of the anti-P49 antibody to perinuclear cytoplasmic vesicles. Forskolin caused these antibody labeled vesicles to migrate from the perinuclear region to the plasma membrane under conditions and with a time course identical to that seen for stimulation of Cl- transport in these cells. Our results suggest that the protein may be a part of a chloride channel complex of secretory epithelial cells. PMID- 1310207 TI - Endothelin-induced calcium responses in human vascular smooth muscle cells. AB - The effects of endothelin-1 (ET) on the cytosolic free Ca (Cai) and cytosolic pH (pHi) were examined in primary cultures of human umbilical artery (HUA) vascular smooth muscle cells (VSMCs), respectively, loaded with fura-2 and 2',7' bis(carboxyethyl)-5(6)-carboxyfluorescein. In 1 mM Ca, ET produced a dose dependent, biphasic increase in the signal with a maximal effect at 400 nM ET. At this concentration, ET produced a Cai transient (mean +/- SE; a rise from basal Cai of 86 +/- 16 to 216 +/- 33 nM) that lasted for approximately 50-60 s. The Cai transient was followed by a slow but sustained increase in Cai. Both ET-induced Cai transient and posttransient Cai were attenuated in Ca deficient medium or by verapamil and nicardipine. In contrast to ET, thrombin elicited only a monophasic Cai response in HUA VSMCs. This response was also partially sensitive to Ca removal or verapamil. KCl (45 mM) depolarization did not elicit a Cai response. However, the presence of voltage sensitive Ca channels in HUA VSMCs was demonstrated by enhanced Mn uptake in cells depolarized with KCl. Both ET and thrombin treatment did not alter pHi. HUA VSMCs demonstrated a single class of ET receptors (approximately 13,000 sites/cell) with an equilibrium dissociation constant of 0.34 nM. Nicardipine did not alter ET binding. These observations suggest a dual effect of ET on the Cai profile in HUA VSMCs that is mediated by Ca mobilization and Ca entry through Ca channels. The Ca entry could include influx through receptor-operated Ca channels, voltage-sensitive Ca channels, or both, but without a direct interaction between ET and these channels. PMID- 1310208 TI - pHi dependence of Na-H exchange and H delivery in IEC-6 cells. AB - The intracellular pH (pHi) dependencies of the Na-H exchanger and also of unidentified acid-loading processes ("H delivery") in IEC-6, a rat intestinal crypt cell line, were determined using microspectrofluorimetry of the pH sensitive dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein on groups of cells grown on glass cover slips mounted in a perfusion chamber in HCO3-free solutions (to inactivate Cl-HCO3 exchange and Na-HCO3 cotransport). Na-H exchange and H delivery rates were measured using two methods. 1) Cells were acid loaded with NH4Cl, and rates of pHi recovery and acidification were measured just before and then just after adding amiloride at various times during the recovery. Multiplying rates of pHi recovery times the intrinsic buffer capacity (beta i) yielded net H efflux rates, rates of pHi decrease (during amiloride treatment) times beta i yielded H delivery rates, and Na-H exchange equals net H efflux plus H delivery. 2) In control cells, time courses of amiloride-induced pHi decreases (from 7.36 to 6.65) and of pHi recovery following amiloride removal (from 6.65 to 7.49) were curve fit by computer; rates of pHi decrease and recovery were calculated; and H delivery, net H efflux, and Na-H exchange were then calculated at the different pHi as above. H delivery and Na-H exchange were both pHi dependent, but in the opposite directions. H delivery was 2-7 mM/min at the control pHi, decreasing to zero around pHi 6.6. Na-H exchange was also equal to 2 7 mM/min at the control pHi, and this increased as pHi decreased; at pHi 6.6, Na H exchange was 20-35 mM/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310209 TI - Regulation of intracellular pH in single rat zona glomerulosa cells. AB - The cytosolic pH (pHi) regulation of rat adrenal zona glomerulosa (ZG) cells was studied using single-cell spectrofluorimetry. Basal pHi was similar for cells incubated in the absence or presence of the HCO3(-)-CO2 buffering system. In the absence of HCO3-, inhibition of the Na(+)-H+ exchanger by dimethylamiloride (DMA) or removal of extracellular Na+ produced substantial acidification of basal pHi. In the presence of HCO3-, neither maneuver affected basal pHi. However, removing extracellular Cl- produced a prompt alkalinization not observed in the absence of HCO3-. Alkalinizing mechanisms were examined by monitoring pHi recovery from an acid load imposed by the NH4Cl pulse technique. In the absence of HCO3-, Na+ removal or DMA addition blocked greater than 80% of pHi recovery. In the presence of HCO3-, 34% of the pHi recovery rate was inhibited by 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 34% by DMA, and 72% by Na+ removal plus DIDS. Therefore both Na(+)-H+ and anion exchangers are active in these cells, working independently to maintain basal pHi. In the absence of HCO3 , Na(+)-H+ exchange is principally responsible for pHi recovery from an acid load. In HCO(3-)-containing medium, such recovery is shared by Na(+)-H+ and Cl(-) HCO3- exchange. PMID- 1310210 TI - Citrate alters Ca channel gating and selectivity in rabbit ventricular myocytes. AB - Addition of 10 mM citrate at constant free extracellular Ca concentration [( Ca]o; 2 mM) reduced contraction in rabbit ventricular muscle and isolated myocytes. We have recently shown that extracellular citrate decreases contraction and Ca current (ICa) in cardiac muscle by a direct effect on Ca channels rather than by Ca buffering per se [D. M. Bers, L. V. Hryshko, S. M. Harrison, and D. Dawson. Am. J. Physiol. 260 (Cell Physiol. 29): C900-C909, 1991]. Citrate rapidly depressed peak ICa and shifted both the peak ICa and the apparent reversal potential (Erev) to more negative potentials. When the impermeant cations, tetraethylammonium or N-methylglucamine were used instead of intracellular Cs, the citrate-induced shift in Erev was reduced or eliminated but depression of ICa was still observed. Thus citrate appears to alter the selectivity (PCa/PCs) of the Ca channel and reduce ICa. We also studied the effects of citrate on Na current through the Ca channel, observed when the divalent cation concentration is submicromolar. This current, termed INS for nonspecific, also exhibited leftward shifts in peak INS and smaller changes in Erev in the presence of citrate. However, neither peak INS nor single-channel conductance were affected by citrate. Thus the reduced PCa/PCs is due primarily to alteration of Ca permeation rather than monovalent cation permeation. Activation and inactivation curves for both ICa and INS were shifted toward more negative potentials by citrate. The shifts in gating and peak current to more negative membrane potentials would be consistent with a surface charge effect. The much larger shift in Erev for ICa (than for INS) is consistent with a reduction in Ca selectivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310211 TI - Thrombin stimulates PDGF production and monocyte adhesion through distinct intracellular pathways in human endothelial cells. AB - Thrombin stimulates multiple functions in cultured endothelial cells (EC), including an increase in cell surface adhesion sites for monocytes and the production of platelet-derived growth factor (PDGF). We have initiated studies to define the intracellular signaling pathways involved in these two thrombin induced EC functions by focusing on the possible roles of the Na(+)-H+ antiporter and guanine nucleotide-binding proteins (G proteins). Amiloride suppressed thrombin-stimulated PDGF production by human aortic EC without affecting either basal PDGF production or overall protein synthesis. The steady-state mRNA levels of PDGF-A and PDGF-B chain were not reduced by amiloride. In replicate EC cultures, amiloride had no effect on thrombin-stimulated monocyte adhesion. In addition, thrombin induction of PDGF production, but not monocyte adhesion, was abrogated in the absence of extracellular sodium. Thrombin stimulation of both monocyte adhesion and PDGF production appeared to involve a pertussis toxin insensitive G protein. Thrombin induced an increase in [35S]guanosine 5'-O-(3 thiotriphosphate) (GTP gamma S) binding to human EC membranes. GTP gamma S, in the presence of a suboptimal concentration of thrombin, caused maximal stimulation of both monocyte adhesion and PDGF production. The effect of GTP gamma S on PDGF production was at the level of transcription. These results indicate that the EC is capable of responding to a pluripotent agonist such as thrombin through multiple signaling pathways, which converge and diverge to achieve differential cellular responses. PMID- 1310212 TI - Regulation of T84 cell monolayer permeability by insulin-like growth factors. AB - When grown on permeable supports, the T84 human colonic epithelial cell line forms polarized monolayer cultures with high-resistance tight junctions between adjacent cells. Addition of either insulin-like growth factor (IGF) I or II to the basolateral but not the apical membrane side of established monolayers caused a dose-dependent decrease in transepithelial resistance over a 4-day period. IGF I was more potent than IGF-II, with half-maximally effective concentrations of 0.7 and 2.2 nM, respectively. Both IGF-I and -II caused a parallel increase in the transepithelial flux rates for Na+ and the extracellular space marker, mannitol, demonstrating that the decrease in electrical resistance was due to increased permeability through the tight junction-regulated paracellular pathway. Simultaneous addition of cycloheximide prevented the decline in electrical resistance, implying that protein synthesis is necessary for the effect of IGF on paracellular permeability. Treatment of monolayers with IGF produced a subtle condensation of the perijunctional actin ring as visualized using rhodamine labeled phalloidin. These results demonstrate that IGF-I and -II regulate the paracellular permeability of T84 cell monolayers through a receptor-mediated process that probably involves changes in protein synthesis and cytoskeletal structure. PMID- 1310213 TI - Hormonal regulation of Cl transport in polar airway epithelia measured by a fluorescent indicator. AB - Cl transport mechanisms in polarized cultures of canine tracheal epithelium were examined using an Ussing-type chamber with independent mucosal and serosal perfusion. Cl activity was monitored continuously from fluorescence of entrapped 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). When added to the serosal (but not mucosal) solution, isoproterenol increased Cl fluxes across the apical membrane Cl more than fourfold. Apical Cl transport was sensitive to diphenylamine-2 carboxylate (DPC) but not to furosemide, whereas basolateral membrane Cl transport was sensitive to furosemide but not to DPC. Based on a mathematical model of Cl transport, we developed a sensitive protocol to measure hormone sensitive Cl transport. In Cl-loaded cells in which basolateral Cl transport was partially inhibited by furosemide, mucosal Cl removal caused no Cl efflux before but rapid efflux (0.25 mM/s) after addition of isoproterenol or chlorophenylthio cAMP. In the presence of indomethacin to block prostaglandin production, elevation of intracellular Ca by bradykinin or 4-bromo-A23187 did not cause Cl efflux, nor did Ca buffering with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N' tetraacetic acid affect stimulation by the cAMP pathway. Phorbol 12-myristate 13 acetate increased Cl efflux submaximally (0.09 mM/s) but did not affect maximal stimulation by cAMP agonists. Methoxamine did not alter apical or basolateral membrane Cl transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310214 TI - Reversed anion selectivity in cultured cystic fibrosis sweat duct cells. AB - The human genetic disease cystic fibrosis (CF) is characterized by defective epithelial Cl- conductance (GCl). To distinguish the CF-affected GCl from other Cl- channels, we have studied the properties of GCl in normal and CF cells grown from explanted reabsorptive sweat ducts (RD). The cultured cells from normal subjects retained some of the typical duct cell properties. The Na+ conductance inhibitor amiloride hyperpolarized intracellular potentials (Vm) by 10.4 +/- 1.6 mV (n = 12). Substitution of gluconate for Cl- depolarized Vm by 15.5 +/- 1.1 mV (n = 33). The apparent GCl (G'Cl) of normal cells was sensitive to adenosine 3',5'-cyclic monophosphate (forskolin, 10(-6) M), as evidenced by a significant increase (63%, n = 9) in the Cl- gradient induced depolarization, and more selective for Cl- than I- (substitution of Cl- by I- depolarized Vm by 6.3 +/- 0.3 mV, n = 49). Although the cells from CF subjects were statistically indistinguishable from normal cells based on Vm (-18.5 +/- 1.2 mV, n = 49 vs. 20.1 +/- 1.8 mV, n = 28), CF cells expressed differences in G'Cl, responses to forskolin, and anion selectivity. CF cells had a significantly reduced G'Cl as indicated by blunted responses to imposed Cl- gradients (26% of normal, n = 28). In contrast to our observations in normal cells, the G'Cl of CF cells was insensitive to forskolin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310215 TI - Modulation of neutrophil activation by okadaic acid, a protein phosphatase inhibitor. AB - We determined the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A), on protein phosphorylation and on the activation of the NADPH oxidase in human neutrophils. In otherwise unstimulated cells, OA induced phosphoprotein accumulation, revealing the presence of constitutively active protein kinases. Pulse-chase experiments in electropermeabilized cells confirmed that this effect was due, at least in part, to inhibition of dephosphorylation. OA potentiated phosphoprotein accumulation induced by phorbol esters and by the chemotactic peptide N-formyl-methionyl leucyl-phenylalanine (FMLP). In phorbol ester-stimulated cells, OA prolonged the respiratory response after inhibition of protein kinase C (PKC) with staurosporine, consistent with a reduced rate of dephosphorylation of active phosphorylated components. Similarly, OA delayed the inactivation of the burst after displacement of FMLP from its receptor by a competitive antagonist. This suggests that the substrates of the protein kinases activated by FMLP are dephosphorylated by PP1 and/or PP2A. That phosphatases control the intensity and duration of the respiratory response is suggested by the finding that OA magnified and prolonged the oxidative burst elicited by FMLP. In contrast, pretreatment with OA produced a time-dependent inhibition of the phorbol ester induced respiratory burst. Under conditions where inhibition of the phorbol ester response was nearly complete, activation by the chemoattractant peptide not only persisted but was in fact accentuated. These findings provide strong evidence that receptor-mediated stimulation of the NADPH oxidase can occur by pathways not involving PKC. PMID- 1310216 TI - Transcellular transport of organic cation across monolayers of kidney epithelial cell line LLC-PK. AB - Transcellular transport and the accumulation of [14C]tetraethylammonium, a typical organic cation, by LLC-PK1 cell monolayers grown on microporous membrane filters were studied. Tetraethylammonium was accumulated progressively in the monolayers from the basolateral side and was transported unidirectionally to the apical side. The transcellular transport of tetraethylammonium was saturable, temperature dependent, and sensitive to the pH of the apical side of the monolayers. The apparent Michaelis constant and maximum velocity values for the transport were 67 microM and 222 pmol.mg protein-1.min-1, respectively. Unlabeled tetraethylammonium, amiloride, procainamide, cimetidine, and choline inhibited the basolateral uptake and transcellular transport of [14C]tetraethylammonium. The development of tetraethylammonium transport activity was observed in the differentiating cells. A sulfhydryl reagent inhibited the tetraethylammonium transport at both the basolateral and apical membranes of the LLC-PK1 cells. These findings suggest that these monolayers possess unidirectional transport systems for organic cations, corresponding to the secretion in the renal proximal tubules. PMID- 1310217 TI - Purinergic receptor activation of Cl- secretion in T84 cells. AB - The regulation by ATP of Cl- secretion in T84 cells grown on filters was investigated by measuring short-circuit current (Isc = net Cl- secretion). ATP (greater than or equal to 10 microM) added to the basolateral side markedly stimulated Isc both in the presence and absence of forskolin-activated Isc. Fluorescence microscopy of cells loaded with the Ca2+ indicator fura-2 showed that ATP stimulated a transient increase in intracellular free Ca2+ concentration [Ca2+]i. The augmentation of forskolin-stimulated Isc by ATP was at least partly caused by mobilization of Ca2+ from an internal store because prior depletion of the store using ionomycin prevented the response. The activity sequence for stimulation of Isc in the presence of forskolin was adenosine 5'-O-(3 thiotriphosphate) = 5'-adenylylimidodiphosphate (AMP-PNP) greater than ATP greater than ADP greater than AMP, suggesting the presence of a P2 purinergic receptor. Neither beta, gamma-methyleneadenosine 5'-triphosphate nor alpha, beta methyleneadenosine 5'-triphosphate increased the Isc. Stimulation of Isc by ATP in the absence of forskolin was at least partly due to the breakdown of ATP to AMP and adenosine, which act at P1 receptors to stimulate Isc, since 1) inhibition of the ecto-phosphohydrolase 5'-nucleotidase by alpha, beta-methylene ADP partially inhibited stimulation of Isc by ATP, 2) the adenosine receptor antagonists caffeine and 8-phenyltheophylline markedly inhibited the ATP stimulated Isc, and 3) AMP-PNP, a weakly hydrolyzable analogue of ATP, caused a much smaller increase in Isc compared with ATP. Adenosine had no effect on [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310218 TI - Effects of an opiate receptor antagonist on renin release in dogs. AB - The present experiments were designed to determine whether blockade of endogenous opiate receptors with naloxone would suppress renin release induced by circulating epinephrine or by reductions of renal perfusion pressure. In the first series of experiments, anesthetized dogs were prepared with a flow probe around the left renal artery and a catheter in the left renal vein, permitting measurement of renin secretion before, during, and after 15-min infusions of epinephrine (50 ng.kg-1.min-1 iv). The epinephrine infusions were conducted either before or after blockade of opiate receptors with naloxone (1 mg/kg iv). Naloxone failed to alter the renin secretory response to intravenous epinephrine infusion. In a second series of experiments, anesthetized dogs were uninephrectomized and prepared with a constrictor cuff around the left renal artery and a renal arterial catheter distal to the cuff. After control measurements of renal perfusion pressure and plasma renin activity (PRA), the cuff was constricted at 15-min intervals to produce controlled stepwise reductions of renal perfusion pressure ranging from 15 to 90 mmHg. One-half of the animals was pretreated with naloxone (1 mg/kg iv). Naloxone pretreatment had no effect on the PRA response to reduced renal perfusion pressure at any pressure. The data fail to support the hypothesis that endogenous opioid peptides are modulators in the control of renin release. PMID- 1310219 TI - Central mineralocorticoid receptor antagonism blocks hypertension in Dahl S/JR rats. AB - The development of hypertension in the S/JR rat is accelerated and exacerbated by a high salt consumption. It has been reported that the intracerebroventricular infusion of RU28318, a selective mineralocorticoid antagonist, at doses that are ineffective when administered subcutaneously, inhibits the development of the hypertension produced by the subcutaneous infusion of aldosterone or deoxycorticosterone in normotensive rats. RU28318 was continuously infused intracerebroventricularly or subcutaneously in Dahl S/JR rats before or after the onset of hypertension induced by a high-salt diet. The centrally infused mineralocorticoid antagonist inhibited the initiation of the increase in blood pressure, when the infusion was started concomitantly with the high-salt diet, and blocked its further increase in rats whose blood pressure had already become significantly elevated with 2 wk of a high-salt diet. The subcutaneously infused mineralocorticoid antagonist had no effect. These data serve to strengthen the hypothesis that the mineralocorticoid receptor in the brain is crucial to the genesis of certain forms of hypertension. PMID- 1310220 TI - Histamine: mercurial messenger in the gut. AB - This review considers the possibility that histamine functions as a cellular messenger in the gastrointestinal tract. Any biological messenger must be produced, received, and responded to, and must have its actions quickly terminated. Histamine is no exception. Histamine synthesis from L-histidine occurs in enterochromaffin-like cells, mucosal mast cells, and nerves. Histamine release occurs through both antibody-dependent and antibody-independent mechanisms. Released histamine interacts with a variety of cellular targets (epithelial cells, smooth muscle cells, endothelial cells, neurons, and a variety of immunocompetent cells). Occupation of H1, H2, and H3 receptors, defined by pharmacological agents, is transduced by different intracellular messengers (Ca2+, cyclic nucleotides) into diverse effects such as secretion, contraction, or modulation of other secretagogues. The responses to histamine are terminated by at least three different mechanisms: metabolic transformation by the actions of methyltransferase and diamine oxidase, desensitization at the receptor level, and cellular uptake. In addition to its well-documented effects as a mediator of inflammatory processes, histamine may also function as a neuro- and immunoregulator. While a significant pathophysiological role for histamine has been realized since the earliest description of its effects, the availability of newer pharmacological agents has permitted a finer dissection of its "physiological" effects and raised the possibility of multiple roles for histamine. PMID- 1310221 TI - An inhibitor of Ca2+/calmodulin-dependent protein kinase II, KN-62, inhibits cholinergic-stimulated parietal cell secretion. AB - Cholinergic stimulation of parietal cell secretion is mediated by an increase in intracellular calcium. KN-62, a selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK II), has recently been synthesized (Tokomitsu et al. J. Biol. Chem. 265: 4315-4320, 1990). To define the role of CaMK II in parietal cell secretion, we determined the effects of KN-62 on secretagogue-stimulated acid secretion in isolated rabbit parietal cells. Pretreatment of parietal cells with KN-62 resulted in the inhibition of carbachol-stimulated [14C]aminopyrine uptake over a concentration range of 3 to 60 microM (IC50 of 20 microM). KN-62 (60 microM) reduced carbachol-stimulated aminopyrine uptake to unstimulated levels. KN-62 did not alter carbachol-stimulated increases in cytoplasmic free Ca2+ concentration. High concentrations of KN-62 (60 microM) elicited a small decrease in aminopyrine uptake stimulated by forskolin, but did not significantly inhibit histamine stimulation. A potent CaMK II activity was identified in total membrane from parietal cells. These results suggest that CaMK II may mediate cholinergic stimulated parietal cell secretion. PMID- 1310222 TI - Vesicle acidification driven by a millionfold proton gradient: a model for acid influx through gastric cell membranes. AB - A delta pH 6 proton (internal pH 7.5, external pH 1.5) was imposed across the bilayer of egg phosphatidylcholine (PC) vesicles. The presence of the gradient was verified by the use of agents that predictably collapsed it. These agents included a detergent (Triton X-100), a pore-forming Na-H+ exchanger (nigericin), and weak acids capable of shuttling protons across the membrane (acetic and acetylsalicylic acids). The magnitude of the proton gradient and the rate of pH gradient collapse were determined by measuring pyranine fluorescence by use of an isosbestic point technique and calculating intravesicular pH from a calibration curve. Acid flux into the vesicles in the presence of chloride was measured directly by a simpler one-wavelength method. p-Xylene-bis-pyridinium bromide (DPX), a pyranine fluorescence quencher, was used to verify that the fluorescence signal originated from within the vesicles and that the observed rates of acidification were not an artifact due to pyranine leakage. Acid flux was found to be dependent on the ionic composition of the buffer. The presence of chloride ion in the external compartment caused a dramatic increase in the rate of acidification. It was demonstrated that the kinetics of acid flux into the vesicle were clearly controlled by the chloride-dependent mechanism at a relatively low chloride concentration of 2.5 mM. The model presented here is a simple and sensitive method for investigating the factors that influence acidification rates across membranes when acidification is driven by extremely large proton gradients, in the presence of chloride; conditions similar to those found in the stomach. PMID- 1310223 TI - Influence of acid secretory state on Cl(-)-base and Na(+)-H+ exchange and pHi in isolated rabbit parietal cells. AB - Parietal cell apical proton secretion is accompanied by apical Cl- secretion, K+ cycling, and the generation of intracellular base. We examined the ability of the parietal cell to maintain intracellular pH (pHi) during its transformation from the resting to the stimulated state and evaluated the ion transport mechanisms involved in the maintenance of ionic equilibrium. Isolated rabbit parietal cells were loaded with the pH-sensitive fluorescent dye BCECF, and pHi was monitored in maximally stimulated, resting (absence of a secretagogue), and omeprazole inhibited cells. Although [14C]aminopyrine (AP) accumulation increased up to 30 fold above basal during stimulation, the mean pHi of maximally stimulated cells was not different from that of inhibited cells both immediately and late after stimulation in an extracellular pH range from 6.2 to 7.8 in either HEPES or CO2/HCO3- buffer. When the stilbene DIDS was added 2 min after stimulation of acid formation, pHi rapidly increased (0.09 +/- 0.02 vs. 0.04 +/- 0.02 pH units in unstimulated cells in 6 min), indicating an increased base efflux through a DIDS-sensitive transporter (most likely the Cl(-)-base exchanger). Stimulation of acid secretion did not change the transport capacity, apparent affinity for extracellular Cl-, or dependency of the anion flux rate on pHi of the DIDS sensitive base exporter. For a given pHi, amiloride-inhibitable proton efflux rates during pHi recovery from an acid load were identical in resting and stimulated cells, suggesting that neither the transport capacity not the pHi set point of the parietal cell Na(+)-H+ exchanger is altered by cAMP-dependent stimulation of acid formation. We conclude that, during the cAMP-mediated stimulation of acid formation in isolated rabbit parietal cells, the pHi remains constant, but an increased base efflux occurs without a change in the transport capacity of the involved base extrusion mechanisms or an inhibition of the parietal cell base loading mechanisms. Whether changes in the intracellular Cl- concentration on stimulation of acid formation initiate the increased base efflux and whether additional ion transporters are involved in the maintenance of ion homeostasis during acid secretion remain to be determined. PMID- 1310224 TI - Regulation of intracellular pH in alveolar epithelial cells. AB - Alveolar type II epithelial cells in adult mammalian lungs actively transport salt and water, secrete surfactant, and differentiate into type I cells under normal conditions and following lung injury. It has become increasingly apparent that, like all epithelial cells, alveolar pneumocytes have evolved specialized ion transport mechanisms by which they regulate their intracellular pH (pHi). pHi is an important biological parameter in all living cells whose regulation is necessary for normal cellular homeostasis. pHi, and the ion transport mechanisms by which it is regulated, may contribute to many cellular processes, including transcellular transport, cell volume and osmolarity regulation, and intracellular transport, cell volume and osmolarity regulation, and intracellular electrolyte composition. Moreover, changes in pHi may serve as intracellular signals for biological processes such as cell growth, proliferation, and differentiation. We review herein the general principles of pHi regulation in epithelia and describe the mechanisms and effects of pHi regulation in alveolar pneumocytes. Many of the critical issues in current pulmonary research involve processes that pHi is most likely to affect, including maintenance of alveolar epithelial barrier integrity, development and maintenance of epithelial polarity, epithelial proliferation and differentiation, and regulation of transepithelial transport with respect to alveolar fluid balance in normal individuals and in those with excess alveolar fluid (i.e., pulmonary edema). Investigations into the regulation of pHi in alveolar pneumocytes and the regulatory effects of pHi in turn on other cellular processes are likely to yield information important to the understanding of lung biology and pulmonary disease. PMID- 1310225 TI - Inositol 1,4,5-trisphosphate, inositide flux rates and pool sizes during smooth muscle relaxation. AB - Decreases in D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] content and changes in inositol phospholipid contents occurred during the time of atropine induced relaxation of swine tracheal smooth muscle contracted with 55 microM carbachol. Decrease in Ins(1,4,5)P3 occurred in a pool which makes up 40% of the total content of this inositol phosphate and which has access to Ins(1,4,5)P3 5 phosphatase and/or 3-kinase. A 50% decrease in this pool occurred at 16 s after addition of atropine and within 6-10 s after inhibition of phospholipase C (PLC). The maximal fall in Ins(1,4,5)P3 occurred at a time when force had only decreased 30% of the maximal response. A phosphatidylinositol 4-phosphate (PIP) pool linked to muscarinic receptor-activation increased 160% after addition of atropine, the maximal response occurring at a time when relaxation was 80% complete. The mechanisms for this increase were the maintained formation of PIP and phosphatidylinositol 4,5-bisphosphate (PIP2) even though PIP2 hydrolysis was inhibited and the apparent chemical equilibrium between PIP and PIP2. PMID- 1310226 TI - Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells. AB - This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of [3H]phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs. PMID- 1310227 TI - Expression of peroxidase activity in rat tracheal epithelial cells associated with Mycoplasma pulmonis. AB - Endogenous peroxidase activity has not been localized in the tracheal mucosal epithelial cells of specific pathogen-free (SPF) rats. After natural infection with Mycoplasma pulmonis in SPF rats, peroxidase activity became localized to the endoplasmic reticulum, nuclear envelope, and Golgi apparatus of tracheal ciliated or mucous secretory cells. Some secretory cells occasionally had peroxidase positive secretory granules. At 1 wk M. pulmonis was found to attach to these epithelial cells, which then showed positive peroxidase activity at 2 wk. Serum antibody titers against M. pulmonis were positive at 5 wk. These results suggest that virulent mycoplasma infection and interaction with the tracheal epithelial cells trigger the de novo expression of peroxidase activity, which seems to play a role in mucosal anti-microbial defense mechanisms. PMID- 1310228 TI - Maturation of cGMP response to ANP by isolated glomeruli. AB - Experiments were done to determine whether there is a maturational increase in production of guanosine 3',5'-cyclic monophosphate (cGMP) by glomeruli or in eggression of cGMP out of glomerular cells. Both preweaned and adult isolated rat glomeruli responded with an acute rise in intracellular cGMP after 0.5-min exposure to 0.1 microM ANP. However, at 4 h extracellular cGMP was significantly greater in ANP-treated adult compared with preweaned glomeruli (P less than 0.005). In the absence of 3-isobutyl-1-methylxanthine (IBMX) intracellular cGMP was significantly higher in preweaned glomeruli (P less than 0.05). Moreover, the specific activity of phosphodiesterases for cGMP hydrolysis was twofold less in preweaned glomerular membranes (P less than 0.004). Finally, probenecid decreased export of adult glomerular cGMP by 60 +/- 4%, whereas preweaned glomerular cGMP export decreased by only 27 +/- 4% (P less than 0.05). In conclusion, compared with adult, ANP-treated preweaned glomeruli export less cGMP out of glomerular cells, have a higher concentration of intracellular cGMP, and have lower cGMP specific phosphodiesterase activity, and the organic ion transporter in preweaned glomerular cells exports cGMP less effectively. The limited transport of cGMP out of preweaned glomeruli may account for the blunted natriuretic and diuretic response following ANP stimulation of young rats. PMID- 1310229 TI - Luminal flow rate regulates proximal tubule H-HCO3 transporters. AB - In vivo microperfusion was used to examine the mechanism of luminal flow rate dependence of proximal tubule acidification. Luminal flow rate was acutely changed between 5 and 40 nl/min, while luminal and peritubular capillary composition were held constant. With inhibition of basolateral membrane base transport by peritubular 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), cell pH (pHi) provides a sensitive index of apical membrane H secretory activity. At a luminal perfusate [HCO3] of 25 mM, progressive increases in luminal flow rate (5----15----25----40 nl/min) caused progressive increases in pHi. This effect was of a smaller magnitude with a luminal perfusate [HCO3] of 60 mM and was further decreased at a luminal perfusate [HCO3] of 100 mM. This pattern of diminished flow rate dependence at higher luminal [HCO3] is consistent with the presence of a luminal unstirred layer, whose composition can be modified by luminal flow rate. The activity of the apical membrane Na-H antiporter, assayed as the initial rate of pHi recovery from an acid load in the presence of peritubular DIDS, was faster at 40 compared with 5 nl/min. Basolateral membrane Na-3HCO3 symporter activity, assayed as the initial rate of pHi recovery from an alkali load in the absence of luminal and peritubular chloride, was faster at 40 compared with 5 nl/min. This effect was eliminated by luminal amiloride, suggesting an indirect effect of flow mediated by changes in pHi secondary to flow rate-dependent changes in apical membrane Na-H antiporter activity. In summary, increases in luminal flow rate directly increase apical membrane H secretion, possibly by modification of a luminal unstirred layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310230 TI - Analysis of K+ transport by rabbit CCD: conductive pathways and K(+)-K+ exchange by Na(+)-K+ pump. AB - We studied the cellular pathways of K+ transport by the rabbit cortical collecting duct that was stimulated to absorb Na+ and to secrete K+. The vast majority of K+ secretion (into the lumen) was inhibited by benzamil, a blocker of epithelial Na+ channels. The residual K+ secretion was completely inhibited by ouabain. Thus all active K+ secretion was dependent on Na+ transport by the Na(+) K+ pump. The passive pathways of K+ transport were further examined using tracer and electrophysiological measurements. K+ transfer across the apical membrane was predominantly or exclusively conductive; the apical K+ conductance was 31 mS/cm2. The basolateral membrane contained two pathways for K+ tracer translocation. The (barium-sensitive) conductive pathway accounted for a relatively small (12-20%) portion of the tracer permeation. A larger pathway appeared to be via K(+)-K+ exchange on the Na(+)-K+ pump. The magnitude of the Ba2(+)-sensitive (basolateral) K+ conductance predicted a substantially larger tracer flux than was actually measured. The best explanation for this difference is the presence of single-file diffusion through K+ channels on the apical and basolateral membranes. An analysis of the electrically silent K+ transport from lumen to bath suggests that the Na(+)-K+ pump can vary the ratio of its Na(+)-K+ and K(+)-K+ modes of operation. When the tubule is actively transporting Na+ and K+, the Na(+)-K+/K(+)-K+ turnover ratio is greater than 7. When Na+ transport is limited by inhibiting Na+ entry across the apical membrane, the ratio falls to less than 1. A major factor determining this ratio is probably the availability of Na+ to the cytoplasmic side of the pump. PMID- 1310231 TI - Superoxide stimulates IP3-induced Ca2+ release from vascular smooth muscle sarcoplasmic reticulum. AB - Reactive oxygen intermediates (ROI) have been implicated in a variety of pathophysiological conditions, and vascular smooth muscle may be a site of damage in such oxygen toxicity. Mechanisms of the effects of these intermediates on vascular smooth muscle at the cellular level, however, have not been well studied. We have previously shown that xanthine oxidase (XO)-generated superoxide radicals (O2-.) inhibited the Ca(2+)-adenosine triphosphatase of vascular smooth muscle sarcoplasmic reticulum (SR) through mechanisms that do not involve H2O2 or hydroxyl radicals. In the present study, we report that the D-myo-inositol 1,4,5 trisphosphate (IP3)-induced Ca2+ release from bovine aortic SR was also affected by O2-(.). Hypoxanthine (100 microM) plus XO (10 mU/ml) in the presence of catalase (100 U/ml) stimulated the IP3-induced Ca2+ release from SR monitored using arsenazo III. At 10 microM IP3, the release was doubled by O2-. treatment. As a consequence of using the higher SR protein concentrations required to observe the Ca2+ release, this effect was independent of Ca2+ uptake inhibition induced by O2-(.). Since the effect of O2-. was not seen when a nonhydrolyzable analogue of IP3 was used to induce Ca2+ release, O-2. may be inhibiting the degradation processes of IP3. PMID- 1310232 TI - Inhibitory effect of pindolol on hypoxic pulmonary vasoconstriction. AB - The effects of a beta-agonist (isoproterenol) and beta-antagonists (propranolol and pindolol) on hypoxic pulmonary vasoconstriction (HPV) and on changes in some chemical mediators were examined in 28 isolated blood-perfused dog lung lobes. Hypoxic challenge (4 min) was repeated twice, and each drug was administered at a bolus dose of 0.2 mg between the hypoxic periods. The first hypoxia increased pulmonary vascular resistance (PVR) by 33% or more in all groups. Both isoproterenol and pindolol inhibited the second HPV completely, but propranolol did not influence HPV. During normoxia, isoproterenol and pindolol significantly decreased PVR by 17.5 and 6.7% (P less than 0.01), respectively, but propranolol had no effect on PVR. In the control and propranolol groups, plasma levels of adenosine 3',5'-cyclic monophosphate (cAMP) significantly decreased during hypoxia, but those of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2 did not change. cAMP increased from 17.0 +/- 4.0 to 76.7 +/- 15.6 pmol/ml in the isoproterenol group (P less than 0.01), and prostaglandin E2 increased from 87.0 +/- 13.6 to 1,015.4 +/- 309.7 pg/ml in the pindolol group (P less than 0.05). The results suggest that the mechanism of HPV inhibition is different between isoproterenol and pindolol. PMID- 1310233 TI - Oxygen radicals, enzymes, and fluid transport through pericardial interstitium. AB - The interstitium is the final link in the transportation of nutrients from the bloodstream to the individual cells of an organism. To assess interstitial fluid transport in normal and inflamed tissue, the hydration (H, ml H2O/g dry wt) and hydraulic conductivity (Kp, 10(-8) cm2.s-1.cmH2O-1) of bovine pericardial stroma were determined. The effect of enzymes and neutrophil-derived products of inflammation on the properties of the interstitial model were determined. Samples of the pericardium were exposed separately to trypsin, elastase, hyaluronidase, collagenase, superoxide radicals, and hydrogen peroxide. After exposure, the tissues were washed repeatedly in physiological saline and equilibrated in transport chambers heated to 37 degrees C and pressurized to 50 cmH2O. Fluid flow across the tissues was monitored. A section of tissue was removed and weighed. The tissue section was subsequently dried and reweighed. Tissue thickness, H, and Kp were calculated. H and Kp of the control tissues were 2.82 +/- 0.04 and 1.71 +/- 0.07, respectively. Hydration was significantly increased (22-38%) by exposure to trypsin, elastase, collagenase, and superoxide radicals. Kp increased significantly (30-1055%) in the groups treated with trypsin, hyaluronidase, collagenase, and superoxide radicals. The inflammatory mediators generally increased the hydration and/or the hydraulic conductivity of the model. These results indicate that neutrophil-derived products could be involved in the development of interstitial edema during the inflammatory process. PMID- 1310234 TI - H2 receptor-mediated responses of aortic endothelial cells to histamine. AB - It is well known that umbilical vein endothelial cells express H1 receptors that mediate the various responses of these cells to histamine, including accumulation of inositol phosphates, rise of cytosolic Ca2+, increased permeability to macromolecules, and release of prostacyclin. In bovine aortic endothelial cells, histamine did not increase the level of inositol phosphates nor the release of prostacyclin. In contrast, it increased the adenosine 3',5'-cyclic monophosphate (cAMP) content of these cells. That response was obtained in the 1 to 100 microM range of concentrations and reached a maximum within 2 min of histamine addition. It was mimicked by the H2-specific agonist dimaprit, inhibited by the H2 antagonist ranitidine, and insensitive to the H1 antagonist mepyramine. Histamine reduced the permeability to albumin of bovine aortic endothelial cell monolayers; this paradoxical effect is likely to be mediated by the rise in cAMP, which is known to enhance the barrier property of the endothelium. In conclusion, bovine aortic endothelial cells are responsive to histamine, and this response is mediated by H2 and not H1 receptors. PMID- 1310235 TI - Cardiovascular and renal actions of C-type natriuretic peptide. AB - Studies were performed in two groups of anesthetized dogs (n = 5 per group) to determine the cardiovascular and renal actions of synthetic C-type natriuretic peptide (CNP). Systemic infusion of CNP (group 1; 10 and 50 ng.kg-1.min-1 iv) resulted in marked cardiovascular hemodynamic effects characterized by a decrease in mean arterial pressure, cardiac output, and atrial pressures in association with a decrease in sodium excretion. Bolus administration of CNP (group 2; 5 micrograms/kg iv) to minimize cardiovascular hemodynamic changes resulted in only a transient decrease in arterial pressure. Sodium excretion decreased despite a return of arterial pressure to baseline. These biological responses were associated with increases in plasma guanosine 3',5'-cyclic monophosphate (cGMP) in both groups but with no change in urinary cGMP. With both systemic infusion or bolus administration of CNP, significant increases in plasma aldosterone were observed in association with increases in distal nephron sodium reabsorption. This study demonstrates that CNP exhibits profound systemic hemodynamic actions and is indirectly, or perhaps directly, antinatriuretic. PMID- 1310236 TI - Evidence for two types of internal Ca2+ stores in canine mesenteric artery with different refilling mechanisms. AB - Novel transient biphasic responses of the dog mesenteric artery to phenylephrine hydrochloride (PE, 10 microM) in Ca(2+)-free medium containing 50 microM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) have been analyzed. The initial component was significantly inhibited by ryanodine (30-100 microM), an agonist enhancing Ca2+ release from the sarcoplasmic reticulum, whereas the second was significantly inhibited by nifedipine (1 microM), and L type Ca2+ channel antagonist, or EGTA, to chelate Ca2+, and was potentiated by BAY K 8644 (1 microM), an L-type Ca2+ channel agonist. After repletion of Ca2+ stores in normal Krebs solution or in high KCl (60 mM) Krebs, the first component was inhibited by cyclopiazonic acid (CPA, 30 microM), a putative, reversible, and selective microsomal Ca2+ pump adenosinetriphosphatase inhibitor. BAY K 8644 potentiated the second component in the presence of CPA. The inhibition of the first component by CPA suggests that the refilling ultimately requires the CPA sensitive Ca2+ pump for Ca2+ resequestration. However, the second component may refill by a CPA-independent route opened by BAY K 8644. These results, taken as a whole, indicate that the biphasic PE response in Ca(2+)-free medium may reflect compartmentalization of Ca2+ storage related to the different routes of refilling. PMID- 1310237 TI - Ontogeny of cholinergic and adrenergic mechanisms in the frog (Rana temporaria) heart. AB - Histochemical techniques, field stimulation, and application of autonomic drugs were used to study neurotransmission in the heart during ontogenesis of Rana temporaria. Cholinesterase (ChE)-containing fibers, fluorescent chromaffinlike cells, and fluorescent fibers were found first in the heart at tadpole stages 40, 40, and 50, respectively. Inhibitory cholinergic and stimulatory adrenergic responses to field stimulation first appeared at stages 39-40 and 42, respectively. Inhibitory responses to acetylcholine (ACh) and stimulatory responses to epinephrine (Epi) were observed as early as stages 31 and 32. The concentrations producing half-maximal response values for both neurotransmitters increased during development. Indirect evidence was obtained that the subsensitivity of tadpole hearts to ACh was due to increased hydrolysis of ACh by tissue ChE and that the subsensitivity of adult frog heart to Epi could be connected with a maturation of the neuronal uptake mechanism. The pA2 values for atropine and propranolol were 10 times greater in tadpoles than in adults. The main conclusion is that the cholino- and adrenoreactive systems appear in the frog heart cells before they become innervated and the sensitivity of these systems to neurotransmitters does not increase with innervation. PMID- 1310238 TI - The role of B1- and B2-kinin receptors in the renal tubular and hemodynamic response to bradykinin. AB - Bradykinin (BK) is known to induce diuresis (UV), natriuresis (UNaV), and increased renal blood flow (RPF) with little or no change in glomerular filtration rate (GFR). In this study, BK is infused alone and concurrently with B1- or B2-kinin receptor antagonists into the left kidney of pentobarbital anesthetized dogs. The intrarenal infusion of BK (bolus: 0.5 microgram/kg, followed by a sustaining dose: 0.05 micrograms.kg-1.min-1) affected left kidney function only. In the left kidney, UV increased from 0.42 +/- 0.21 to a maximum of 1.88 +/- 0.55 ml/min (P less than 0.01) and UNaV rose from 55 +/- 13 to 160 +/ 17 mueq/min (P less than 0.01), while RPF was enhanced from 86 +/- 11 to 125 +/- 24 ml/min (P less than 0.05), and GFR remained unchanged. When a B1-receptor antagonist ([Leu8]-des-Arg9-BK; 2.0 micrograms.kg-1.min-1) was infused concurrently with BK, the increase in urine flow was not different from BK alone. UNaV was transiently attenuated by 50% in this group (P less than 0.05). A B2 receptor antagonist (D-Arg0,[Hyp3,D-Phe7]-BK; 2.0 micrograms.kg-1.min-1) infused with BK significantly (P less than 0.05) and selectively inhibited by 50% the maximal diuresis provoked by BK alone. UNaV in this group was not different from that induced by BK alone. Finally, the concurrent infusion of either B1- or B2 antagonist completely inhibited the rise in RPF observed when BK was infused alone. We conclude that BK infused into the renal artery of dogs in vivo can alter UV and UNaV independently of global renal hemodynamic (RPF and GFR) changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310239 TI - Endothelin-1 potentiation of angiotensin II stimulation of aldosterone production. AB - Endothelin-1 (ET-1) binds to specific receptors in cultured bovine adrenal glomerulosa cells and stimulates aldosterone secretion with a 50% effective concentration (EC50) of 300 +/- 80 pM (mean +/- SE). The relative stimulatory potency for ET-1 is significantly less than that of angiotensin II (ANG II). The incubation of calf zona glomerulosa cells in primary culture with ET-1 and ANG II resulted in a significant potentiation of ANG II effect on aldosterone secretion. The EC50 of ET-1 potentiation of ANG II-induced stimulation of aldosterone secretion was 40 +/- 5 pM (mean +/- SE, n = 4), which is lower than the EC50 for ET-1 stimulation of aldosterone secretion. Adrenocorticotropic hormone (ACTH) stimulation of aldosterone secretion, but not that of potassium, was also potentiated by ET-1, but to a lesser degree. ET-1 and ET-1-mediated potentiation of ANG II-stimulated aldosterone biosynthesis increased both the early and late pathways of aldosterone biosynthesis, but the potentiation was greater for the early pathway. Preincubation with ET-1 for at least 15 min, followed by extensive washing to remove bound ET-1, also resulted in persistent potentiation of ANG II mediated aldosterone secretion. ET-2, sarafotoxin, and vasoactive intestinal contractor potentiation of ANG II action were very similar to that of ET-1. ET-3 and Big-ET-1 potentiated ANG II stimulation only at the highest doses tested and the proendothelin-(110-130) fragment was inactive. ET-1 potentiation of ANG II action is likely to be mediated through an ETB receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310240 TI - Immunohistochemical identification of aggregated actin filaments in formalin fixed, paraffin-embedded sections. I. A study of infantile digital fibromatosis by a new pretreatment. AB - Some authors have claimed that actin is not immunostained in characteristic intracytoplasmic inclusions of infantile digital fibromatosis, whereas others have claimed that it is. Formalin-fixed specimens were used in the former studies; specimens fixed in alcohol used in the latter studies. Actin at other sites, such as the rim of the inclusions, was distinctly immunostained even in the formalin-fixed specimens. Such phenomena make it difficult to accept the loss of antigenicity of actin as a result of formalin fixation. The use of usual pretreatment with trypsin provided the same results. We were able to immunostain actin distinctly and strongly in the inclusions for the first time in formalin fixed specimens by combining KOH in 70% ethanol and trypsin. This successful staining results from the adequate etching effect of trypsin, which occurs because of a loosening of proteins in the inclusions due to KOH. These phenomena suggest that steric hindrance of antigen determinant has occurred only in the inclusions as a result of intramolecular cross-linkage, because of extremely dense accumulation of actin filaments in the inclusions. PMID- 1310241 TI - Frequency of Epstein-Barr viral DNA in "Western" sinonasal and Waldeyer's ring non-Hodgkin's lymphomas. AB - Sinonasal non-Hodgkin's lymphomas (SNHL) of B- or T-cell immunophenotype have been associated with the Epstein-Barr virus (EBV) in Asian patients. We investigated eight sinonasal and 10 Waldeyer's ring NHL from Western patients for evidence of EBV genomes using a sensitive in situ hybridization technique. EBV DNA was detected in each of three sinonasal NHL with a T-cell immunophenotype and two of five cases with a B-cell immunophenotype. Two of 10 B-cell Waldeyer's ring NHL were positive for EBV genomes. In each positive case, EBV genomes were evenly distributed among the neoplastic cells, whereas no evidence of EBV in associated nonneoplastic lymphocytes or epithelium was seen. The results indicate that B cell and T-cell sinonasal NHL are associated with EBV in Western as well as in Asian patients, and that EBV may have a role in oncogenesis in NHL of the upper aerodigestive tract. The strong association of EBV with nasopharyngeal carcinoma suggests that the anatomic site is important in the development of EBV-related neoplasms. PMID- 1310242 TI - Meal-induced jejunal absorption requires intact neural pathways. AB - A signal for meal-induced absorption originates from the small intestine and is transmitted to a luminally excluded segment of the proximal jejunum (Thiry-Vella [TV] fistula). Using intraluminal topical anesthesia with oxethazaine, this study assessed the role of intestinal neural pathways in basal and postprandial jejunal water and electrolyte absorption. Studies (n = 45) were performed on dogs with 25 cm proximal jejunal TV fistulae and feeding jejunostomies, using luminal perfusion with 14C-polyethylene glycol. The animals were randomized into five study groups: (1) jejunostomy oxethazaine alone, (2) jejunostomy water and jejunal meal, (3) jejunostomy oxethazaine and jejunal meal, (4) TV fistula water and jejunal meal, and (5) TV fistula oxethazaine and jejunal meal. The jejunal meal significantly increased TV fistula absorption, whereas oxethazaine significantly reduced basal absorption when administered via the TV fistula and postprandial absorption when administered via the jejunostomy (p less than 0.05). TV fistula oxethazaine did not diminish the magnitude of postprandial absorption. We conclude that intact intestinal neurotransmission is necessary for maintenance of the normal basal absorptive state of the proximal jejunum and for the generation of a normal meal-stimulated proabsorptive signal from the small intestine. A nonneural mechanism appears to be of predominant importance in transmitting the proabsorptive signal from the intact gastrointestinal tract to the TV fistula. PMID- 1310243 TI - The HIV-infected health care worker: another AIDS policy conundrum. PMID- 1310244 TI - Hepatitis C after needlestick injuries. PMID- 1310246 TI - Female adnexal tumor of wolffian origin. AB - We describe a female adnexal tumor of probable wolffian origin with stage 2B disease. The presence of peritoneal implants suggests a more aggressive clinical course than is usually expected. We present the findings of light microscopic and ultrastructural evaluation as well as those of immunohistochemical and DNA ploidy analysis, which, to our knowledge, have not been previously described for this type of tumor. PMID- 1310245 TI - Herpes simplex hepatitis before and after acyclovir treatment. Immunohistochemical and in situ hybridization study. AB - A healthy 20-year-old woman developed herpes simplex virus (HSV) hepatitis. The diagnosis was made by needle biopsy of the liver, and the patient was intravenously treated with acyclovir for 15 consecutive days (total dose, 21 g). The liver biopsy specimen and liver tissue obtained at autopsy were processed for immunoperoxidase staining with rabbit anti-HSV and for DNA-DNA in situ hybridization. The liver biopsy tissue revealed massive necrosis of hepatocytes, which were strongly positive for HSV with both immunoperoxidase and in situ hybridization methods. The liver tissue obtained at autopsy showed regenerative nodules of hepatocytes, surrounded by connective tissue stroma. Within the connective tissue there were completely necrotic hepatocytes, which were positive for HSV with the immunoperoxidase method but almost completely negative with the in situ hybridization method, except for a very few HSV DNA-positive hepatocytic nuclei. It was concluded that immunoperoxidase staining with anti-HSV is a sensitive method with which to detect ongoing and previous HSV infection, whereas the in situ hybridization method is specific for HSV-DNA from viable HSV. PMID- 1310247 TI - Giant cystosarcoma phyllodes of the prostate associated with adenocarcinoma. AB - Cystosarcoma phyllodes of the prostate is a rare neoplasm, occurring in adult men. It closely resembles the not uncommon tumor of the female breast and usually behaves in a similar manner. This case of benign cystosarcoma phyllodes of the prostate occurred in a 53-year-old man who presented with increasing abdominal girth and underwent exploratory laparotomy and removal of the 11.2-kg tumor. It was remarkable for its very large size and the presence of foci of well differentiated adenocarcinoma, prostatic acinar type. The glandular epithelium of both the phyllodes tumor and the carcinoma were immunoreactive for cytokeratin, epithelial membrane antigen, prostate-specific antigen, and prostate-specific acid phosphatase. The presence of typical prostatic type adenocarcinoma and this immunoreactivity pattern strongly supports a prostatic origin for this rare neoplasm. PMID- 1310248 TI - Manipulations of the renin-angiotensin system and intake of a sweetened alcoholic beverage among rats. AB - Standard laboratory rats were maintained on a daily regimen involving deprivation of fluids for 22 h followed by a 2-h opportunity to drink water and a sweetened alcoholic beverage. Angiotensin II, in doses ranging from 0.1 to 1.25 mg/kg, dose relatedly decreased rats' mean intake of ethanol. All doses increased rats' mean intake of water. Angiotensin II, 0.25 mg/kg, reliably reduced intake of ethanol when it was presented alone during the 1st h of the daily 2-h drinking session, and reliably increased intake of water when it was subsequently presented alone during the 2nd h. Thus the reduction in intake of ethanol seen when the alcoholic beverage is presented concurrently with water is probably not merely due to the increase in intake of water. Lisinopril, an angiotensin converting enzyme inhibitor, in doses of 0.3, 1.0, and 3.0 mg/kg, dose relatedly decreased intake of ethanol, but only after several days of injections. Concurrent intake of water was increased dose relatedly. When injections of lisinopril ceased, intakes of both ethanol and water took several days to return to control levels. Pretreatment with lisinopril, 3.0 mg/kg, for 8 days, had no effect on subsequent intakes of either water or ethanol. Lisinopril, 3.0 mg/kg, had no effect on rats' intake of a sweet solution without ethanol. These results confirm previous work and extend the data base supporting the idea that the renin-angiotensin system plays a role in modulating intake of ethanol. PMID- 1310249 TI - Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide. AB - The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6 glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu 1 or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained. PMID- 1310250 TI - Chemotherapy of non-small cell lung carcinoma guided by an in vitro drug resistance assay measuring total tumour cell kill. AB - Specimens from 45 patients with previously-untreated non-small cell lung cancer (NSCLC) were tested for in vitro chemosensitivity to ten drugs utilising the DiSC assay, which measures cell kill in the total (largely non-dividing) tumour cell population. Thirty-five assays were successful and 25 patients with advanced disease subsequently received chemotherapy with the 'best' three drugs selected by the assay. Six patients were Karnofsky performance status 60 or less and the median pretreatment weight loss was 8.5%. Nine patients had a partial response (response rate = 36%; 95% confidence interval = 17-55%) and the median survival of all patients was 202 days. Specimens from responding patients were significantly more sensitive in the assay to drugs in general (especially to etoposide and to 'natural product' drugs) and to the drugs used in treatment than were specimens from non-responding patients. In vitro drug resistance differences between responding and non-responding patients were of greater significance than were differences between other clinical and laboratory measurements. Assay results classified patients into two cohorts, having relatively high and low probabilities of responding to chemotherapy. Assay results also identified patient cohorts with above average and below average durations of survival. Five patients (20%) were found to have tumours with extreme drug resistance (EDR), defined as assay results for the average of all ten tested drugs falling greater than one standard deviation more resistant than the median for all tumours assayed, and none of these patients with EDR responded to chemotherapy. PMID- 1310251 TI - Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma. AB - Mouse monoclonal antibodies PAb 240 and PAb 1801 which specifically immunoprecipitate p53 protein, were used to examine 27 fresh ovarian tumours (16 serous adenocarcinomas, six endometrioid carcinomas, one mucinous adenocarcinoma, one mucinous borderline tumour and three benign adenomas). Eleven out of 16 (69%) serous adenocarcinomas and one endometrioid tumour showed positive staining with one or both antibodies and none of the mucinous or benign tumours stained with either antibody. DNA from tumour and peripheral blood leukocytes was used to identify allelic deletions on chromosome 17p in tumours. 11/12 positively staining tumours showed less of heterozygosity (LOH) on 17p at the nearest informative locus to the p53 gene. In this series of ovarian tumours, LOH on 17p correlates closely with the aberrant expression of the p53 protein in a high proportion of advanced stage serous adenocarcinomas. This observation suggests that the p53 tumour suppressor gene is involved in the evolution of epithelial ovarian cancer (EOC) and may have prognostic significance. PMID- 1310252 TI - Three types of human lung tumour cell lines can be distinguished according to surface expression of endogenous urokinase and their capacity to bind exogenous urokinase. AB - This study evaluates the cell surface expression of urokinase-type plasminogen activator (u-PA) and the capacity to bind exogenous urokinase as possible parameters for the distinction of various types of human lung tumours. Twelve different tumour cell lines including four small cell carcinoma, two large cell carcinoma, three squamous cell carcinoma, one adenocarcinoma and two mesothelioma cell lines of lung origin were investigated. Surface expression of endogenous u PA was determined in a cellular radioimmunoassay (CRIA) using the u-PA-specific monoclonal antibody 98/6. To estimate additional u-PA binding capacity, exogenous two-chain, 54 kDa u-PA was employed in the CRIA. The influence of phorbol ester (PMA) treatment on expression and binding of these molecules was studied. Three different groups of lung tumour cell lines could be distinguished according to their expression of u-PA and u-PA-binding ability: (i) non small cell lung carcinoma (NSCLC) cell lines of squamous cell carcinoma/adenocarcinoma origin expressed small amounts of u-PA and bound little u-PA. Large cell carcinoma cell lines expressed high amounts of u-PA and bound large amounts of u-PA. In general, expression of u-PA and u-PA binding was enhanced after PMA treatment. (ii) Mesothelioma cell lines did not express u-PA, but were able to bind u-PA. (iii) Small cell carcinoma (SCLC) lines were devoid of surface-expressed u-PA and could not bind u-PA, both under untreated and PMA-treated conditions. It could thus be demonstrated that these three groups of lung tumour cell lines differ in their ability to express u-PA and to bind external u-PA. This may reflect the different in vivo growth behaviour and origin of the respective tumour groups. PMID- 1310254 TI - Relation between exposure to respirable silica dust and silicosis in a tungsten mine in China. AB - To estimate the quantitative relation between exposure to respirable silica dust and risk of an attack of silicosis, 1151 workers exposed to silica dust and employed from 1958 to 1987 in a tungsten mine in China were investigated. The results showed that the ratio of respirable silica dust concentration to total silica dust concentration was 0.529. Then, the total silica dust concentration in historical surveillance and monitoring data was converted to respirable silica dust concentration. The free silica content in respirable dust determined by x ray diffraction averaged 24.7%. Multiple logistic regression was used for the dichotomous dependent variables (presence or absence of silicosis). The independent variables in the multiple logistic regression with presence of silicosis as the dependent variable were age when first exposed, tuberculosis (presence or absence), and cumulative exposure to respirable silica dust. The partial regression coefficient of individual cumulative exposure was estimated as 0.079. It implied a positive association between exposure to respirable silica dust and risk of an attack of silicosis. The exposure limit for respirable silica dust was estimated as 0.24 mg/m3 under given conditions. PMID- 1310253 TI - Non-invasive assessment of human tumour hypoxia with 123I-iodoazomycin arabinoside: preliminary report of a clinical study. AB - Non-invasive predictive assays which can confirm the presence or absence of hypoxic cells in human tumours show promise for understanding the natural history of tumour oxygenation, and improving the selection of patient subsets for novel radiotherapeutic strategies. Sensitiser adducts have been proposed as markers for hypoxic cells. Misonidazole analogues radiolabelled with iodine-123 have been developed for the detection of tumour hypoxia using conventional nuclear medicine techniques. In this pilot study, we have investigated one such potential marker, 123I-iodoazomycin arabinoside (123I-IAZA). Patients with advanced malignancies have undergone planar and single-photon emission computed tomographic (SPECT) imaging after intravenous administration of 123I-IAZA. We have observed radiotracer avidity in three out of ten tumours studied to date. Normal tissue activity of variable extent was also seen in the thyroid and salivary glands, upper aerodigestive tract, liver, intestine, and urinary bladder. Quantitative analysis of those images showing radiotracer avidity revealed tumour/normal tissue (T/N) ratios of 2.3 (primary small cell lung carcinoma), 1.9 (primary malignant fibrous histiocytoma) and 3.2 (brain metastasis from small cell lung carcinoma) at 18-24 h post injection. These preliminary data suggest that the use of gamma-emitter labelled 2-nitroimidazoles as diagnostic radiopharmaceuticals is feasible and safe, and that metabolic binding of 123I-IAZA is observed in some, but not all tumours. The inference that tumour 123I-IAZA avidity could be a non invasive measure of tumour hypoxia deserves independent confirmation with needle oximetry. PMID- 1310255 TI - Obstructive jaundice. PMID- 1310256 TI - Diffusible factors in vertebrate embryonic induction. PMID- 1310257 TI - Oscillation of MPF is accompanied by periodic association between cdc25 and cdc2 cyclin B. AB - Activation of maturation-promoting factor at the onset of mitosis requires the tyrosine dephosphorylation of one of its components, the cdc2 protein kinase. cdc25 is the specific tyrosine phosphatase that activates cdc2. We find that Xenopus oocytes contain a relative of cdc25, p72. In Xenopus embryos the abundance of p72 does not oscillate during the cell cycle. However, p72 directly associates with cdc2-cyclin B in a cell cycle-dependent manner, reaching a peak at M phase. The M phase kinase that associates with p72 is catalytically active. These results suggest that the mechanism by which cdc25 triggers cdc2 activation involves a periodic physical association between cdc25 and the cyclin B-cdc2 complex and also that mitotic control can be affected by mechanisms other than transcriptional regulation of the cdc25 gene. PMID- 1310258 TI - Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. AB - Resident luminal endoplasmic reticulum (ER) proteins carry a targeting signal (usually KDEL in animal cells) that allows their retrieval from later stages of the secretory pathway. In yeast, the receptor that promotes this selective retrograde transport has been identified as the product of the ERD2 gene. We describe here the properties of a human homolog of this protein (hERD2). Overproduction of hERD2 improves retention of a protein with a weakly recognized variant signal (DDEL). Moreover, overexpression of KDEL or DDEL ligands causes a redistribution of hERD2 from the Golgi apparatus to the ER. Mutation of hERD2 alters the ligand specificity of this effect, implying that it interacts directly with the retained proteins. Ligand control of receptor movement may limit retrograde flow and thus minimize fruitless recycling of secretory proteins. PMID- 1310259 TI - Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. AB - We have purified and cloned a HeLa cell nuclear protein that strongly stimulates binding of retinoic acid and thyroid hormone receptors (RARs and TRs) to response elements. The purified protein is a human retinoid X receptor beta (hRXR beta). Three murine members of the RXR family (mRXR alpha, beta, and gamma) have also been cloned, and their interactions with RARs and TRs have been investigated. Under conditions where RAR, RXR, and TR bound poorly as homodimers to various response elements, strongly cooperative RAR-RXR and TR-RXR binding was observed. The binding efficiency was dependent on the sequence, relative orientation, and spacing of the repeated motifs of response elements. We show also that unstable RAR-RXR heterodimers were formed in solution, and that C-terminal sequences and the DNA-binding domains of both receptors were required for efficient formation of stable heterodimers on response elements. These findings suggest a convergence of the signaling pathways of some members of the nuclear receptor superfamily. PMID- 1310260 TI - 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. AB - All-trans retinoic acid (RA) has previously been shown to modulate the transcriptional properties of the retinoic acid receptor (RAR) and retinoid X receptor (RXR). The inability of all-trans RA to bind to RXR suggests that it may be metabolized to a more active high affinity ligand. We report here an experimental approach that has identified 9-cis RA as an RXR ligand. It is up to 40-fold more potent than all-trans RA in transfection assays and binds with high affinity. The production of 9-cis RA in cultured cells and the identification of this molecule in liver and kidney demonstrates the existence of this molecule in living organisms. The discovery of this novel hormone points to the key role retinoid metabolism may have in generating new signaling pathways. PMID- 1310261 TI - A diacylglycerol kinase is involved in the regulation of interleukin-2 synthesis in Jurkat T cells. AB - Diacylglycerol (DAG) plays a prominent role in several activation processes because of its ability, in the presence of calcium ions and phosphatidylserine, to activate C kinase. In T lymphocytes, however, DAG, produced in response to activating mAb or lectins, is rapidly metabolized into phosphatidic acid (PA) which may participate in further steps of activation. We thus investigated the involvement of a DAG kinase in several events subsequent to the activation of Jurkat T cells by CD3 mAb or phytohemagglutinin (PHA). We showed that three inhibitors of DAG kinase abrogated PA production and impaired calcium release from intracellular compartment, restored phosphatidylserine synthesis, and finally blocked IL-2 production in CD3- and PHA-stimulated cells. Postactivation DAG levels were not modified and DAG kinase inhibitors lowered IL-2 secretion even in the presence of phorbol ester that directly activates the C kinase. These results clearly demonstrate that, beside the effect of DAG on C kinase, DAG kinase dependent production of PA is crucial for further steps of T cell activation. PMID- 1310262 TI - Impairment of macrophage activation and granuloma formation by protein deprivation in mice. AB - Protein-calorie malnutrition predisposes to infection by intracellular pathogens, but the basis for this predisposition is unclear. We studied the effect of protein deprivation on mouse peritoneal macrophage function and on granuloma formation during infection by bacille Calmette-Guerin (BCG). Injection of lipopolysaccharide (LPS) to induce inflammation elicited fewer peritoneal cells from mice fed a 2.5% protein diet than from mice fed an isocaloric chow in which protein calories constituted 24% of the total. LPS-elicited macrophages from protein-deprived mice demonstrated a reduction in spreading, total cell protein, cell lactate dehydrogenase, and release of superoxide anion (O2-) in response to stimulation. Priming in vitro by interferon (IFN)-gamma for enhanced release of O2- was also significantly impaired in protein-deprived mice. This defect was reversible by repletion with 24% protein diet for 10 days. Impairment of macrophage function in protein-deprived mice was further evidenced by an impaired capacity to express Ia antigen in response to IFN-gamma and by reduced production of IL-1 activity in response to LPS. Infection by BCG in protein-deprived mice was characterized by impaired granuloma development in liver, lungs, and spleen. Thus, in this model, protein deprivation significantly impaired macrophage activation, as assessed by morphologic, metabolic, and functional criteria. This impairment might compromise immune effector mechanisms dependent on macrophage activation, including rejection of intracellular pathogens. PMID- 1310263 TI - Alterations of DNA content in human endometrial stromal cells transfected with a temperature-sensitive SV40: tetraploidization and physiological consequences. AB - The normal genomic stability of human cells is reversed during neoplastic transformation. The SV40 large T antigen alters the DNA content in human endometrial stromal cells in a manner that relates to neoplastic progression. Human endometrial stromal cells were transfected with a plasmid containing the A209 temperature-sensitive mutant of SV40 (tsSV40), which is also defective in the viral origin of replication. Ninety-seven clonal transfectants from seven different primary cell strains were isolated. Initial analysis revealed that 20% of the clonal populations (19/97) had an apparent diploid DNA content, 35% (34/97) had an apparent tetraploid DNA content, and the remainder were mixed populations of diploid and tetraploid cells. No aneuploid populations were observed. Diploid tsSV40 transformed cells always give rise to a population of cells with a tetraploid DNA content when continuously cultured at the permissive temperature. The doubling of DNA content can be vastly accelerated by the sudden reintroduction of large T antigen activity following a shift from non-permissive to permissive temperature. Tetraploid tsSV40 transfected cells have a lower capacity for anchorage-independent growth and earlier entry into 'crisis' than diploid cells. These results indicate that during the pre-crisis, extended lifespan phase of growth, the SV40 large T antigen causes a doubling of DNA content. This apparent doubling of DNA content does not confer growth advantage during the extended lifespan that precedes 'crisis'. PMID- 1310264 TI - IRMA and RIA compared for assessing dexamethasone suppression of corticotropin in plasma. PMID- 1310265 TI - Negative interference by ethamsylate in enzymatic assay of serum creatinine involving peroxidase-coupled reaction. PMID- 1310266 TI - Hydroxyl radical-induced characteristic chemiluminescent spectra from plasma of hemodialysis patients. AB - Plasma from hemodialysis patients evoked weak photon emissions (chemiluminescence) in a characteristic emission spectrum with a peak at 430 nm, attributed to attack by hydroxyl radicals generated from the iron-catalyzed breakdown of hydrogen peroxide (Fenton reaction), whereas plasma from normal healthy subjects showed a rather weak red chemiluminescence peak at around 680 nm, similar to that resulting from attack by hydroxyl radicals. However, the addition of hydrogen peroxide in the absence of divalent irons induced almost the same red chemiluminescent emission spectrum in both plasmas. The HPLC-gel filtration chromatography carried out with both plasmas revealed that a primary emitter evoking a peak emission at 430 nm was located in the fraction of lower molecular-mass substances in fractionated plasma from hemodialysis patients. In contrast, the elution peaks evoking red chemiluminescence with the addition of hydrogen peroxide were mainly observed for the higher-molecular-mass fraction, as determined by gel chromatography of both plasmas. Therefore, the observation of a chemiluminescence peak at 430 nm, induced by the generation of hydroxyl radicals, correlated well with chemiluminescent emissions in plasma samples from patients with chronic renal failure. Spectral analyses of clinical samples that show weak chemiluminescence by forced oxidation by such an active oxygen may provide a new and more sensitive method for diagnosing metabolic disorders. PMID- 1310268 TI - Eccrine acrospiroma of the external auditory canal. AB - Tumors of the external auditory canal include osteomas, ceruminomas, sebaceous cysts, keloids, basal cell carcinomas, squamous cell carcinomas, and, in rare cases, eccrine acrospiromas. We describe an eccrine acrospiroma arising from the distal external auditory canal, which was associated with decreased hearing on the affected side. Surgical resection of the tumor resulted in improved hearing. PMID- 1310267 TI - Serum steroid hormonal profiles by reversed-phase liquid chromatography in patients with 17-hydroxylase deficiency and in an affected family. AB - We used an optimized isocratic reversed-phase high-performance liquid chromatographic procedure to separate and measure 12 steroid hormones, and studied the steroid hormone profiles in sera from three patients with 17 hydroxylase deficiency (17-OHD). Two of the patients were sisters, one of whom (II-3), expressing normotension and primary amenorrhea, was diagnosed on the basis of chromatographic data and followed up for seven years. The untreated patients had obvious abnormalities on chromatograms of serum extracts, characterized by markedly increased corticosterone (B) and decreased or undetectable cortisol (F) and cortisone (E). The concentration of 11 deoxycorticosterone was much greater in the patient with classical symptoms than in the normotensive patient. In all three patients, concentrations of aldosterone were within the normal range, but concentrations of progesterone were much lower than in the patients with 21-hydroxylase deficiency. We evaluated the responses to corticotropin and dexamethasone. HPLC evaluation of the serum steroid profiles before and after corticotropin stimulation in the affected family showed that in the parents and one other sibling, concentrations of F before and after stimulation were within the normal ranges. The sums of the ratio of B to F before and the ratio of B to F after corticotropin stimulation (sigma B/F) in the parents and the other sibling were 0.292, 0.496, and 0.614, respectively, all much higher than the normal value (mean +/- SD: 0.164 +/- 0.038). Thus the sigma B/F value may be a hormonal marker of heterozygotes carrying this defect. PMID- 1310269 TI - Familial adenomatous polyposis: results following ileal pouch-anal anastomosis and ileorectostomy. AB - To compare the clinical and functional results of ileorectostomy (IR) and ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP), we reviewed the results of 94 IPAA patients and 21 IR patients who were operated upon between 1978 and 1988. The groups were similar with respect to age and sex. None of the patients died postoperatively. Postoperative complications occurred in 28 percent of the IPAA group and in 17 percent of the IR group (P greater than 0.1). Seven percent of IPAA patients described symptoms compatible with pouchitis. Sixty-one percent of IR patients required subsequent fulguration of rectal polyps at least once. IR patients had a mean (+/- SD) of 4 (+/- 2) stools per day, while IPAA patients had 5 (+/- 2) stools per day (P greater than 0.05). No significant difference in daytime soiling was present between IR (6 percent) and IPAA (4 percent). Nighttime spotting was also similar between the two groups. Nighttime soiling, however, was reported by 4 percent of IPAA patients but not by IR patients (P less than 0.05). One IPAA patient (1 percent) required pouch excision for a desmoid tumor, while two IR patients (11 percent) required proctectomy and ileostomy for recurrent dysplastic polyps (P less than 0.05). Adhesions and a shortened ileal mesentery prevented the construction of an ileoanal procedure in these latter patients. In conclusion, the postoperative complication rate and functional results are similar after IR and IPAA in patients with FAP; however, IR does not eradicate rectal polyps and may indeed preclude IPAA for those requiring subsequent proctectomy. PMID- 1310270 TI - Noncytotoxic drug therapy for intra-abdominal desmoid tumor in patients with familial adenomatous polyposis. AB - Forty of 416 patients with familial adenomatous polyposis were noted to have intra-abdominal desmoid tumors, and a subgroup of 16 were treated with noncytotoxic drug therapy. Drugs used were sulindac (14 patients), sulindac plus tamoxifen (3 patients), indomethacin (4 patients), tamoxifen (4 patients), progesterone (DEPO-PROVERA; Upjohn Co., Kalamazoo, MI) (2 patients), and testolactone (1 patient). Therapy with these drugs for continuous periods of six months or more resulted in three complete and seven partial remissions. When treated patients were compared with untreated patients (n = 12), there were significant benefits for the treated group, both in reduction of desmoid size and in improvement of symptoms, despite the inherent selection bias against this. Sulindac was the only drug used in enough patients to permit independent evaluation of its effect, with one complete and seven partial reductions of tumor size. Some patients had a delayed response to sulindac, with tumor shrinkage occurring after an initial period of tumor enlargement. When using sulindac for the treatment of desmoid tumors, this phenomenon should be considered. PMID- 1310271 TI - Highly malignant carcinoma in chronic ulcerative colitis without preceding dysplasia or DNA aneuploidy. Report of a case. AB - A 41-year-old female with a history of total ulcerative colitis for 15 years is presented. After eight years, she was enrolled in a colonoscopic surveillance program with regular examinations every second year and with biopsy sampling for histologic assessment of dysplasia as well as for flow cytometric analysis. Neither dysplasia nor DNA aneupoloidy developed during the course of the follow up, but, after seven years, the patient developed a rapidly growing malignant stricture in the lower rectum. At the time of diagnosis, a local gluteal metastasis was found. Following preoperative radiation therapy, laparotomy disclosed a rectal cancer with local growth in the pelvis. Despite an attempt to perform curative surgery, the patient deteriorated and died within four months after the diagnosis. The carcinoma was of a poorly differentiated, mucinous, signet ring cell type, and DNA analyses of both the tumor and its metastases were diploid. Retrospective analyses of mucin content in colonoscopic biopsies showed a gradual shift from sulfated mucin to sialomucin. This case underlines the fact that even rigorous follow-ups offer no absolute guarantee against incurable malignancy in surveillance programs for ulcerative colitis despite the inclusion of DNA analyses. PMID- 1310272 TI - Effects of neutrophils in rat luteal cells. AB - Ovarian function may be modulated by cells of the immune system. We have investigated the role of neutrophils (polymorphonuclear leukocytes) on rat luteal cell function. Activated neutrophils inhibited LH-sensitive cAMP accumulation, which was dependent on neutrophil cell number. At a concentration of 10(6) neutrophils/ml and 10(5) luteal cells/ml, LH-stimulated cAMP accumulation was inhibited by 50%. The inhibitory effect of activated neutrophils was reversed by superoxide dismutase (SOD) and catalase. LH-stimulated progesterone production was also inhibited by activated neutrophils. Progesterone production by 10(5) luteal cells was inhibited approximately 20% in the presence of 10(6) activated neutrophils, and this inhibition was blocked by SOD and catalase. Conditioned medium from activated neutrophils also produced inhibitory effects on LH stimulated cAMP accumulation and progesterone production, which could be reversed by SOD and catalase. The phosphodiesterase inhibitor isobutylmethylxanthine had no significant effect on the inhibition of cAMP accumulation by conditioned medium from activated neutrophils. Luteal cells loaded with a fluorescent indicator for determining intracellular reactive oxygen species (dichlorofluorescein diacetate) showed increased fluorescence in the presence of activated neutrophils. No increase in fluorescence occurred in the absence of neutrophils or in the presence of SOD and catalase. These studies demonstrate that reactive oxygen species produced by activated neutrophils can enter the luteal cell and cause antigonadotropic effects. Although the experimental model used in the present studies may not be truly physiological, the data demonstrate that neutrophils may play a role in functional and structural regression of the corpus luteum in the rat. PMID- 1310273 TI - Calcium: its role in alpha 1-adrenergic stimulation of atrial natriuretic peptide secretion. AB - alpha 1-Adrenergic agonists increase atrial natriuretic peptide (ANP) secretion. The mechanism of alpha 1-adrenergic-stimulated secretion is not known. In this study we examine the calcium dependency of alpha 1-agonist-stimulated ANP secretion. Isolated superfused rat left atria paced at 2 Hz were used for study. Superfusion with 10 microM phenylephrine increased ANP secretion by 2-fold. Lowering the superfusate calcium concentration from 1.8 to 0.2 mM totally negated the secretory response to phenylephrine. To determine whether this reflected a reduction in calcium influx, reduced calcium release from the sarcoplasmic reticulum (SR), or both, atria were superfused with 1 microM ryanodine, an inhibitor of SR calcium release. Ryanodine had no effect on phenylephrine stimulated ANP secretion. Atria were superfused with 10 microM nitrendipine to determine whether calcium influx through voltage-dependent calcium channels was a mechanism of calcium entry for stimulation. Nitrendipine inhibited phenylephrine stimulated ANP secretion by 49% without interfering with alpha 1-adrenergic antagonist receptor binding. This finding was supported by the observation that phenylephrine-stimulated secretion was 52% lower in nonbeating atria. alpha 1 Adrenergic agonists have been reported to enhance Na-H antiporter activity. To determine whether the resulting rise in intracellular sodium may alter Na-Ca exchange to raise intracellular calcium levels, atria were superfused with the Na H antiporter inhibitor, 5-(N,N-hexamethylene)amiloride. Superfusion with 25 microM 5-(N,N-hexamethylene)amiloride did not inhibit phenylephrine-stimulated ANP secretion. Lastly, the calcium dependency of the maintenance of an established response to phenylephrine was examined. Atria were superfused with phenylephrine in buffer containing 1.8 mM calcium for 45 min, followed by superfusion with phenylephrine in 0.2 mM calcium for 30 min. There was no fall in phenylephrine-stimulated secretion by atria superfused in 0.2 mM calcium. In contrast, addition of the alpha 1-adrenergic antagonist phentolamine induced an immediate fall in phenylephrine-stimulated ANP secretion. We conclude that 1) calcium influx is necessary to initiate alpha 1-agonist-stimulated ANP secretion; 2) calcium release from the SR does not play a role in alpha 1-agonist-stimulated secretion; 3) calcium entry through L-type calcium channels is responsible for half of the calcium influx; 4) enhanced Na-H antiporter activity does not play a role in alpha 1-agonist-stimulated secretion; and 5) maintenance of alpha 1 agonist-stimulated secretion is not dependent on calcium influx. PMID- 1310274 TI - Rat melanin-concentrating hormone stimulates adrenocorticotropin secretion: evidence for a site of action in brain regions protected by the blood-brain barrier. AB - Melanin-concentrating hormone (MCH) is a peptide reported to inhibit ACTH and cortisol secretion in teleost fish. Its ability to modify the activity of rat corticotrophs, however, remains controversial. We report here that while the peripheral injection of rat (r) MCH failed to alter plasma ACTH levels of conscious rats with an intact blood-brain barrier (BBB), it significantly activated the hypothalamic-pituitary-adrenocortical axis of rats with increased BBB permeability induced by protamine sulfate administration into the internal carotid artery. Similarly, the intracerebroventricular injection of this peptide into rats with intact BBB measurably released ACTH. The ACTH response to rMCH was markedly, but not totally, inhibited by passive immunoneutralization of CRF. These results indicate that rMCH acts within the central nervous system to stimulate the hypothalamic-pituitary-adrenocortical axis of rats, and that the site of action of the peptide is located in brain structures protected by the BBB. Activation of CRF-secreting neurons represents an important final pathway, although other regulatory factors also seem to be involved. PMID- 1310275 TI - The placental lactogen receptor in maternal and fetal sheep liver: regulation by glucose and role in the pathogenesis of fasting during pregnancy. AB - To clarify the roles of glucose and insulin in the regulation of the PL receptor in fetal and maternal sheep liver, we administered iv glucose to pregnant ewes during a 72-h fast. The binding of ovine PL (oPL) to hepatic membranes from glucose-infused ewes and their fetuses was compared with the binding of oPL to tissues of fasted, saline-infused sheep and sheep fed normally ad libitum. Fasting of pregnant ewes caused a 58-70% reduction in the number of PL receptors in fetal and maternal liver. Intravenous administration of glucose during fasting increased the number of PL receptors in fetal liver by 137.4%. In contrast, glucose administration during fasting had no effect on the number of PL receptors in maternal liver. The number of PL binding sites in fetal liver correlated positively with fetal weight (r = 0.59) and length (r = 0.54) and with fetal plasma glucose (r = 0.69) and insulin (r = 0.55) concentrations. In contrast, PL binding was inversely related to fetal plasma oPL concentrations (r = -0.70). These findings suggested that glucose, insulin, and/or oPL may regulate PL binding in the ovine fetus. To determine whether glucose or insulin exert direct effects on the PL receptor in ovine fetal tissues, we examined the binding of radiolabeled oPL to ovine fetal hepatocytes and fibroblasts in culture. The specific binding of oPL to fetal hepatocytes was low and variable (1.0 +/- 0.5%) and it was not possible to assess reliably the effects of glucose or insulin supplementation. The specific binding of oPL to fetal fibroblasts (5.4 +/- 0.6%/mg) was unaffected by variations in media glucose concentrations (5.5-16.5 mM) or by pretreatment with insulin (10-1000 ng/ml). The results of these studies demonstrate that glucose and other nutritional factors regulate the expression of the PL receptor in fetal and maternal sheep liver. Alterations in PL binding play roles in the metabolic adaptation of the mother and fetus to nutritional deprivation and stress. PMID- 1310276 TI - 12-O-tetradecanoylphorbol-13-acetate inhibits osteoclast-like cell differentiation in rat bone marrow cultures by inducing macrophage polykaryons. AB - The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) at 10(-9) M stimulated the formation of osteoclast-like multinucleated cells (MNCs) in the presence of 1 alpha,25-dihydroxyvitamin D3 in rat bone marrow cultures. However, at 10(-7) M, it clearly inhibited 1 alpha,25-dihydroxyvitamin D3-dependent osteoclast-like MNC formation at 6 days of culture. In cultures treated with 10( 7) M TPA, numerous MNCs that lack the marker enzyme tartrate-resistant acid phosphatase (TRAP) were formed. These TRAP-negative MNCs had neither receptors for calcitonin nor dentine-resorbing activity. The reactivity of the cells against antirat macrophage antibodies was completely different from that of authentic osteoclasts. These data suggest that TRAP-negative MNCs formed in the presence of 10(-7) M TPA are macrophage polykaryons. Time-course studies showed that 10(-7) M TPA stimulated osteoclast-like MNC formation at 4 days of culture, but these osteoclast-like MNCs were converted to TRAP-negative MNCs. Furthermore, 1-(5-isoquinolinyl-sulfonyl)2-methylpiperazine (H-7), a protein kinase-C inhibitor, inhibited osteoclast-like MNC formation in a dose-dependent fashion. These results suggest that activation of protein kinase-C may play a role in osteoclast differentiation. PMID- 1310277 TI - Effect of parathyroid hormone on arachidonic acid metabolism in mouse osteoblasts: permissive action of dexamethasone. AB - We examined the regulation of arachidonic acid (AA) metabolism in primary cultures of mouse osteoblasts under steady state and after acute stimulation by PTH. Both dexamethasone-treated and untreated cells were evaluated, as glucocorticoids are known to modulate some actions of PTH in osteoblasts and to affect arachidonic acid metabolism in cells in general. Cells were labeled with [3H]AA for 3 h, followed by a 20-h equilibrium period, then exposed to 10(-8) M PTH for different time periods ranging from 2-60 min. The results showed that although osteoblasts maintained in vitro in the absence of dexamethasone were responsive to PTH, as measured by cAMP production (50-fold increase), PTH had no effect on the distribution of AA in phospholipids and did not induce the release of free AA from phospholipid pools. After 7-day treatment of the cells with 4 x 10(-7) M dexamethasone, 15-min PTH stimulation resulted in a significant increase in free AA within the cells (mean +/- SE, +142 +/- 11%; n = 9) and a short-lived change in the distribution of AA within cellular phospholipids (phosphatidylethanolamine, -63 +/- 3%; phosphatidylinositol, +168 +/- 7%; phosphatidylserine, +296 +/- 50%; sphingomyelin, +220 +/- 20%; lysophosphatidylcholine, +634 +/- 31%; mean +/- SE; n = 3), despite the fact that no changes in PTH-induced cAMP production were observed. Because the release of free AA is an essential step in the production of eicosanoid metabolites that could act as second messengers, these findings suggest that corticosteroid treatment may activate signal transduction pathways for PTH which are latent in untreated cells, and thereby explain at least in part the profound effects of corticosteroids on osteoblast function. PMID- 1310279 TI - Modulation of kidney function in conscious Pekin ducks by atrial natriuretic factor. AB - The influence of avian atrial natriuretic factor (ANF) on renal function was examined in conscious saltwater-acclimated Pekin ducks undergoing a steady state diuresis maintained by iv infused isotonic avian Krebs-Ringer solution at a rate of 1.0 ml/min. Synthetic chicken ANF (chANF) was applied iv at doses of 10, 50, and 90 ng/min.kg BW for 10 min and caused dose-dependent transient increases in urine flow, osmolal excretion, glomerular filtration rate, effective renal plasma flow, and fractional water clearance at decreased urinary osmolality. Using receptor autoradiography, binding sites for [125I]Bolton-Hunter-labeled chANF [( 125I]BH-chANF) were localized in both the reptilian-type glomeruli and the collecting duct system throughout the duck kidney. A RRA for [125I]BH-chANF, established using an enriched kidney membrane fraction, indicated that unlabeled chANF and human ANF competitively displaced [125I]BH-chANF with comparable potencies. ANF-induced modulation of renal salt and water elimination via glomerular and tubular receptor interactions is consistent with the concept that this hormone has a physiological role in avian volume homeostasis. PMID- 1310278 TI - The effect of muscarinic cholinergic agonists on intracellular calcium and progesterone production by chicken granulosa cells. AB - The effects of the muscarinic cholinergic receptor agonist carbachol on intracellular calcium ion concentration ([Ca2+]i) and progesterone production was determined in granulosa cells from the two largest preovulatory follicles of laying hens. [Ca2+]i was measured in cells loaded with the calcium-responsive fluorescent dye fura-2. Resting [Ca2+]i was 96 +/- 5 nM (n = 13). There was a 4- to 8-fold increase in [Ca2+]i in 85% (n = 80) of the cells within 10 sec after the addition of a maximally stimulating concentration (2 mM) of carbachol. The initial [Ca2+]i spike was followed by a sustained, but lower, calcium elevation, with superimposed oscillations which returned to resting level after several minutes. Both phases of the calcium transient were inhibited by pretreating the cells with atropine (1 microM), pirenzepine (2 microM) or 4-diphenylacetoxy-N methylpiperidine methiodide (1 microM). The sustained phase of the response with its superimposed oscillations, but not the initial spike, was inhibited by pretreating the cells with the calcium channel blockers lanthanum (1 mM), cobalt (5 mM), or methoxyverapamil (50 microM), or by incubating the cells in calcium free medium. Nifedipine (0.5-20 microM) did not affect the carbachol-induced calcium transient. 8-(N,N-Diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (50 microM) blocked the sustained-oscillatory phase of the carbachol-induced [Ca2+]i transient, but did not affect the initial spike when added before carbachol (2 mM). Despite its ability to stimulate [Ca2+]i surges, carbachol (10(-6)-10(-3) M) did not affect basal or LH-stimulated cAMP or progesterone production in 24-h cultures. These studies demonstrate that activation of chicken granulosa cell muscarinic receptors causes a rapid increase in [Ca2+]i through the release of Ca2+ from intracellular stores, followed by a sustained elevation of Ca2+ with superimposed oscillations caused by the influx of extracellular Ca2+. These results also indicate that an increase in [Ca2+]i in chicken granulosa cells does not alone stimulate steroidogenesis, since the carbachol-induced increases in [Ca2+]i were not accompanied by increased progesterone production. PMID- 1310280 TI - Stage-specific binding of inhibin and activin to subpopulations of rat germ cells. AB - Flow cytometry was used to separate and identify Sertoli and germ cell populations in primary rat testicular cultures derived from animals of different ages on the basis of cell size and DNA and lipid content. Multiparameter fluorescent evaluation of each cell preparation resulted in the assignment of specific staining patterns to Sertoli cells (diploid, high lipid content), spermatogonia (diploid, low lipid content), spermatocytes (large, tetraploid, high lipid content), and round spermatids (haploid, low lipid content). Each field was separately analyzed for inhibin and activin binding. Fluorescein isothiocyanate-conjugated activin bound with greatest intensity to spermatogonia, with little binding to leptotene or zygotene spermatocytes. Fluorescein isothiocyanate-conjugated inhibin bound to all stages of germ cells tested. Cross competition data indicate that at least two and probably three distinct receptors exist for these peptides. PMID- 1310281 TI - Luteinizing hormone-releasing hormone and neuropeptide Y influence deoxyribonucleic acid replication in three anterior pituitary cell types. Evidence for mediation by growth factors released from gonadotrophs. AB - Treatment of anterior pituitary reaggregate cell cultures from 14-day-old female rats with physiological doses of the gonadotropin-releasing hormone LHRH or neuropeptide Y (NPY) for 40 h dose-dependently increased [3H]thymidine ([3H]T) incorporation into DNA of cells expressing PRL immunoreactivity (PRL-ir) and of those expressing ACTH-ir, whereas these peptides decreased the number of [3H]T labeled cells expressing GH-ir. The effects of NPY were of the same magnitude as those of LHRH. The effects of LHRH were not seen in a gonadotroph-deprived cell population obtained by sequential velocity and buoyant density gradient sedimentation. When the latter cell population was coaggregated with purified gonadotrophs from 14-day-old rats, LHRH did enhance [3H]T labeling of lactotrophs and decreased that of somatotrophs. Gonadotroph-conditioned medium obtained by continuous perifusion of gonadotroph-rich reaggregates contained four different high molecular weight substances mimicking the effects of LHRH and NPY on [3H]T incorporation in the respective pituitary cell types. These substances were partially purified and separated from each other by concentration on a Bond-elut C18-reversed phase cartridge, ultrafiltration, and C18-reversed phase HPLC. One factor stimulated [3H]T labeling of lactotrophs, another that of corticotrophs, and two others inhibited [3H]T labeling of somatotrophs. The present data suggest that the development of PRL-, GH-, and ACTH-containing cells in the pituitary is modulated by LHRH and/or NPY and that the action of LHRH and probably also of NPY is mediated by specific paracrine growth factors released from gonadotrophs. PMID- 1310282 TI - Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes. AB - Islet amyloid polypeptide (IAPP) is a 37-amino acid peptide shown to be cosecreted with insulin from the pancreatic beta-cells. We have investigated the existence and characteristics of IAPP binding sites in the rat. Specific binding sites for [125I]IAPP were found to be highest in the lung followed by the stomach fundus, spleen, brain stem, hypothalamus, and the liver, respectively. The interaction of [125I]IAPP with its binding site was rapid and temperature dependent, displaying optimum binding at 4 C. This may be explained by the rapid degradation of the label observed at 22 C and 37 C, as determined by fast protein liquid chromatography analysis, and also degradation of the receptor at 37 C. Binding of [125I]IAPP was rapidly dissociated by the addition of 200 nM unlabeled peptide. The presence of nonmetabolizable GTP-gamma-S (0.5 microM) reduced binding, thus suggesting the coupling of the binding site to a G protein. Rat IAPP displaced [125I]IAPP displaying an IC50 of 5.75 x 10(-9) M (mean, n = 4). Displacement was also seen with human IAPP (IC50 = 5.53 x 10(-8) M), human alpha calcitonin gene-related peptide (CGRP) (IC50 = 3.8 x 10(-8) M), rat alpha-CGRP (IC50 = 9.0 x 10(-7) M), and rat beta-CGRP (IC50 = 5.53 x 10(-8) M); suggesting an IAPP-specific binding site. Scatchard plots for rat IAPP binding in the lung gave a dissociation constant of 10.4 +/- 2.63 nM (mean +/- SE, n = 4) and maximal binding of 3.1 +/- 0.97 pmol/mg (mean +/- SE, n = 4), displaying a single class of binding site. Chemical cross-linking analysis showed binding of IAPP to sites of Mr 67,000, 64,000, and 38,000. These findings suggest that specific IAPP binding sites exist which differ from the CGRP receptors in rat tissues. This indicates a possible novel autocrine/paracrine role for IAPP. PMID- 1310283 TI - Indirect evidence to suggest that prolactin mediates the adrenal action of haloperidol to stimulate aldosterone and corticosterone secretion in rats. AB - The effect of dopamine-antagonists on steroid secretion has revealed conflicting results regarding the confirmation of in vivo findings in vitro. In order to discriminate in vivo systemic and local action of the dopamine-antagonist haloperidol (HAL) on aldosterone and corticosterone secretion, microdialysis of the adrenal cortex in conscious, freely moving rats was employed. The effects of 2.5 mg HAL ip or intraadrenal dialysis of 20 micrograms/ml HAL in rats with an intact pituitary gland on PRL, aldosterone, and corticosterone secretion were examined. Systemic HAL application resulted in a 40-fold increase in PRL secretion and stimulated aldosterone and corticosterone production significantly. In contrast, intraadrenal dialysis of HAL had no effect on the secretory pattern of PRL or either steroid hormone, indicating no direct drug action on cells of the rat adrenal cortex. Similarly, ip injection of 2.5 mg HAL in hypophysectomized rats did not alter PRL or steroid hormone levels. We conclude that the dopamine-antagonist HAL stimulates aldosterone and corticosterone secretion in rats through a pituitary factor, probably PRL, but not through direct effects at the adrenal cortex. PMID- 1310284 TI - The effect of insulin-induced hypoglycemia on gene expression in the hypothalamic pituitary-adrenal axis of the rat. AB - This study has examined the effects of insulin-induced hypoglycemia on expression of the CRH, arginine vasopressin, and POMC genes and corresponding peptides in freely moving, unanesthetized, male Sprague-Dawley rats. Animals were infused with 150 mM NaCl for 3 days before the experimental day and were then administered insulin (4 U/kg) or saline iv. In one experiment animals were killed 0, 30, 60, or 90 min after insulin or saline, and RNA was isolated from anterior pituitary, cerebral cortex, and punches of the hypothalamic paraventricular and supraoptic nuclei. In a second experiment, animals were killed 90 min after insulin or saline treatment, and RNA was isolated from whole hypothalami. RNA was analyzed by Northern blot. Plasma glucose fell from 106 +/- 5 to 38 +/- 2 mg/dl after insulin administration and remained low for the duration of the experiment. Plasma levels of ACTH, corticosterone, and vasopressin were 10-, 6-, and 4-fold higher, respectively, in the insulin-treated vs. control animals (by analysis of variance, P less than 0.0001 in all cases), while plasma CRH was unchanged. During hypoglycemia POMC mRNA levels were 1.8-fold higher in the insulin-treated group (by analysis of variance, P less than 0.025). In contrast, paraventricular nucleus, whole hypothalamic, and parietal cortex CRH mRNA and vasopressin mRNA were unchanged. These data support previous studies which indicated that POMC gene expression is increased by hypoglycemia. However, we found no evidence for an increase in paraventricular nucleus or cerebral cortex CRH mRNA expression during hypoglycemia-associated stimulation of the hypothalamic-pituitary-adrenal axis, suggesting that another factor(s) may mediate the observed increase in POMC gene expression. PMID- 1310285 TI - Neonatal status convulsivus, spongiform encephalopathy, and low activity of Na+/K(+)-ATPase in the brain. AB - The first and second child of a family died from neonatal seizures with no detectable brain malformation, metabolic, infectious, or chromosomal etiology. Neuropathological examination of the brain of the second child who died at 11 days revealed a widespread spongy state and a selective vulnerability of the astrocytes characterized by numerous enlarged bare astrocytic nuclei and different forms of astrocyte degeneration. The glial cells were strongly positive for glial fibrillary acidic protein and vimentin immunocytochemical reaction. Cortical measurement of Na+/K(+)-ATPase revealed very low enzyme activity. We hypothesize that a defect of Na+/K(+)-ATPase of the astrocytes could be the common pathogenetic factor for the congenital status convulsivus and for the spongy state. PMID- 1310287 TI - Regulation of Mg2+ uptake in isolated rat myocytes and hepatocytes by protein kinase C. AB - A large Mg2+ cell uptake against concentration gradients is stimulated in collagenase-dispersed rat myocytes by carbachol and in hepatocytes by carbachol or vasopressin. The signalling pathway(s) responsible for this stimulation of Mg2+ uptake was investigated by using various activators or inhibitors of protein kinase C (PKC) and by correlating Mg2+ uptake with cell PKC activity and cAMP content. In both cell preparations, the direct stimulation of PKC by diacylglycerol analogs or phorbol esters reproduce the same pattern of Mg2+ uptake as that induced by carbachol or vasopressin. These data indicate that the activation of PKC is responsible for a stimulation of Mg2+ uptake by myocytes or hepatocytes, whereas increase in cAMP in these cells stimulates Mg2+ release. PMID- 1310286 TI - Biotinyl analogues of amylin as biologically active probes for amylin/CGRP receptor recognition. AB - Biotinyl analogues of rat amylin were synthesised with sulfosuccinimidyl 2 (biotinamido) ethyl-1,3-dithiopropionate (NHS-SS-Biotin). Biotinylated amylin peptides were purified by HPLC, quantitated, and the presence of the biotin group at Lys-1 confirmed by peroxidase-labelled avidin and FAB mass spectroscopy. Amylin-biotin retained a similar affinity for binding to rat liver plasma membranes compared with rat amylin and also completely inhibited insulin stimulated glycogen synthesis in rat soleus muscle incubated in vitro. These biologically active amylin probes will enable a complete analysis of amylin/CGRP receptor expression in various cell types and facilitate the isolation and characterisation of the hormone-receptor complex. PMID- 1310288 TI - Differential regulation of metalloprotease steady-state mRNA levels by IL-1 and FGF in rabbit articular chondrocytes. AB - The expression of collagenase and stromelysin is believed to be coordinately regulated. In this report however, we provide evidence that suggests subtle differences may exist in the early events of the induction of these enzymes. Rabbit articular chondrocytes treated with interleukin-1, either alone or in combination with fibroblast growth factor, accumulated steady-state mRNA levels for both the enzymes, with the latter treatment more effective in inducing greater levels and within a shorter time. Further, the induction of the enzymes by either protocol was blocked by cycloheximide co-treatment. Cycloheximide added 1 h post-stimulation with interleukin-1 + fibroblast growth factor failed to block stromelysin mRNA expression, but was able to block collagenase steady-state mRNA levels. Transforming growth factor-beta, another inhibitor of metallprotease induction, showed no such differential activity. The results suggest that collagenase and stromelysin may have subtle variations in their induction pathways. Our studies further show that the enzyme induction by interleukin-1 alone or in combination with fibroblast growth factor occurs through different, but related mechanisms. PMID- 1310289 TI - In vivo electron paramagnetic resonance spectroscopy/imaging: First experiences, problems, and perspectives. PMID- 1310290 TI - Oxidation of cytosolic NADH by the malate-aspartate shuttle in HuH13 human hepatoma cells. AB - 1. The reoxidation of cytosolic NADH was studied in a line of human hepatoma cells (HuH13) whose mitochondria preferentially utilized glutamine for ATP formation. 2. The tumor cells showed mitochondrial reoxidation of NADH, as evidenced by the accumulation of pyruvate, when incubated aerobically with L lactate. The involvement of the respiratory chain was demonstrated by the addition of specific inhibitors. 3. Glutamine oxidation proceeded in the tumor mitochondria exclusively via a pathway involving transamination. Malate stimulated aspartate production from glutamine. 4. When the tumor cells were cultured in Eagle's medium with aminooxyacetate or in the absence of glutamine, a marked reduction in the cellular NAD/NADH ratio was observed. 5. These results indicate that the malate-aspartate shuttle was functioning in the tumor cells. PMID- 1310291 TI - Theoretical study about the variability of the genome of foot-and-mouth disease viruses. AB - 1. The possibilities of change in amino acids of a protein are discussed in terms of a point mutation. 2. Whereas Met and Trp are forced to change due to a point mutation, other amino acids (Ala, Arg, Gly, Leu, Pro and Val) have a probability of 1/3 to survive in the sequence. 3. On basis of these considerations, the genome from 5 strains (CSP, C3Ind, O1K, A10 and A12) of the foot-and-mouth disease virus was studied. 4. A hypothetical genealogic tree for these strains is suggested, where CSP and C3Ind are close and also A10 and A12. O1K is closer to A10 and A12 than to CSP or C3Ind. PMID- 1310292 TI - Giant axonal neuropathy with predominant central nervous system manifestations. AB - The authors describe a 25-year-old woman with giant axonal neuropathy (GAN) and severe CNS involvement. She had been admitted to hospital with generalized seizures, and had gait disturbances followed by progressive mental deterioration since childhood. Neurological examination revealed mental retardation, scanning speech, cerebellar dysfunction, pyramidal signs, mainly in the lower extremities, and peripheral sensory neuropathy. Sensory nerve conduction velocity was decreased; brain CT and MRI showed diffuse demyelination. Sural nerve biopsy revealed characteristic signs of GAN. The patient's older sister had died at the age of 23, after having had similar neurological disturbances since childhood. This case illustrates an unfamiliar presentation of GAN, characterized by mild sensory neuropathy and serve CNS involvement, including seizures. PMID- 1310293 TI - Chronic progressive epilepsia partialis continua of childhood: Rasmussen syndrome. PMID- 1310294 TI - Cloning and characterization of a novel human cDNA that has DNA similarity to the conserved region of the collagenase gene family. PMID- 1310295 TI - Gene analysis and Epstein-Barr viral genome studies of Hodgkin's disease. PMID- 1310296 TI - Hodgkin's disease: analysis of cell line data. PMID- 1310297 TI - Pilot study of an extended range of potential etiologic agents of diarrhea in the Israel Defense Forces. PMID- 1310298 TI - Experiments on glass-absorbed polonium-210. PMID- 1310299 TI - Results of the intercalibration study of laboratories involved in assessing the environmental consequences of the Chernobyl accident. AB - Within the framework of the International Chernobyl Project, the IAEA's Seibersdorf Laboratories organized an intercalibration exercise among some of the laboratories which were involved in assessing the environmental contamination in the USSR due to the accident. The objective was to assess the reliability of the radioanalytical data for food and environmental samples, which were used to assess the doses. In the initial study reference materials from the stocks of the IAEA's Analytical Quality Control Services (AQCS) were re-labelled and submitted to 71 laboratories as blind samples. These natural matrix materials included samples of milk (containing 2 different levels of radioactivity), soil, air filters and clover. The concentrations of radionuclides in these samples were known from previous intercalibration exercises. The overall range in performance was broad, which is similar to what has been observed in previous international intercomparisons. The results obtained by gamma-ray spectrometry tended to be somewhat underestimated, on average. On the other hand, the laboratories showed an overall tendency to overestimate 90Sr and possibly 239Pu, which were analysed radiochemically. The intercalibration exercise is continuing with nine materials, including: soil, grass, hay and milk powder contaminated with fallout from the Chernobyl accident. These materials, which were prepared by laboratories in the USSR, are now being tested by AQCS prior to future intercomparison exercises. Work with these materials is expected to continue for several years. PMID- 1310301 TI - Environmental radioactivity measurement intercomparisons in the UK. AB - The results of two recent (1989 and 1990) nationwide radioactivity-measurement intercomparisons covering a range of pure beta- and beta/gamma-emitting radionuclides are presented. Over fifty laboratories took part in the first exercise and, in general, the results were satisfactory although most laboratories confined themselves to gamma-ray measurements only. There were some areas of concern, notably decay-scheme data, statements of uncertainty and cascade-summing effects. A follow-up meeting was held to discuss these points with the participants. As a result of this meeting, a second exercise was held, covering a different range of nuclides at lower-activity levels and seeking to discover how participants had improved their procedures in the light of the results from the first exercise. The overall results of the two exercises are reviewed in the light of i) UK radioactivity-monitoring arrangements and ii) the National Measurement Accreditation Scheme (NAMAS). PMID- 1310300 TI - Procedures for the assay of alpha-particle emitters in water samples. AB - In this paper the problems associated with the "in situ" concentration techniques using MnO2 and Al2O3 as adsorbents are reviewed. Sampling equipments, radiochemical separation procedures, yield tracers, sources preparation and counting methods are described. The different behaviour of Ra, U, Th, Pu and Am is discussed and considered for future speciation studies. PMID- 1310302 TI - Measurements of actinide gut-transfer factors in humans. AB - Measurements have been made of the gastrointestinal absorption in humans of 239Np and 242Cm administered together in citrate media. Using five volunteers, consistent results of (2.0 +/- 0.2) x 10(-4) and (1.7 +/- 0.3) x 10(-4) were obtained for Np and Cm respectively; the quoted uncertainties are the standard errors of the means. A progress report is given of work to measure the f1 value for Pu in humans. Early work suggests an f1 value of 2 x 10(-4). PMID- 1310303 TI - Radioanalytical studies of fallout 63Ni. AB - Fallout of Nickel-63 (T1/2 = 100 a) produced in small amounts at nuclear weapon tests following the neutron activation of weapon construction material was investigated by studying carpets of lichen collected during 1961 to 1988 at the Lake Rogen district in central Sweden (62.3 degrees N, 12.4 degrees E). The maximal level of 63Ni in the lichen carpet, which occurred in 1964, was about 0.6 Bq kg-1, dry weight, and decreased to 0.1 Bq kg-1 in 1988. The deposition pattern for 63Ni was similar to other fallout radionuclides such as 137Cs, 90Sr and 239 + 240Pu. The concentrations of stable Ni were relatively constant at 0.5 to 1.0 microgram g-1 throughout the years resulting in, for example, a specific activity (63Ni/stable Ni) of 0.5 Bq mg-1 in 1964 and 0.1 Bq mg-1 in 1988. The total area content of 63Ni was estimated to be 1.0 Bq m-2 and the activity ratio 63Ni/60Co was estimated to be 0.03 in 1966. The Chernobyl accident in April 1986 did not significantly increase the levels of 63Ni. For the measurement of these extremely low-levels of 63Ni, 200 g of dry material (about 1 kg fresh) were ashed and leached with aqua regia after hydroxides had been precipitated with ammonia, leaving Ni in the aqueous phase. Nickel was extracted as a dimethylglyoxime complex by chloroform and back-extracted with HCl. Finally, Ni was electroplated onto copper discs from an ammonium sulfate medium at high pH. The radiochemical yield was determined by atomic absorption spectrometry of stable Ni before and after electrodeposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310304 TI - The measurement of technetium-99 and iodine-129 in waste water from pressurized nuclear-power reactors. AB - The program for measuring the dispersal presence of contaminating nuclides in waste streams produced by pressurized-water-reactor (PWR) power plants required the establishment of analytical procedures for a number of nuclides. In this report the procedure to assess 99Tc and 129I content in liquid samples using liquid-scintillation counting is presented. 99Tc and 129I are adsorbed on AG 1 X2 ion-exchange resin. 129I is then eluted with NaOCl and further purified by liquid liquid extraction using carbon tetrachloride and an aqueous solution of sodium thiosulphate. 99Tc is eluted with hot nitric acid (6 M/60 degrees C). If necessary any 60Co present in the sample is separated by liquid-liquid extraction of the cobalt-TTA complex with iso-BuOH. The overall recovery yield is 96.5 +/- 2.5% for 99Tc and 90.1 +/- 6.2% for 129I. Finally beta-activity is measured by liquid-scintillation counting. A limit of detection of 5 Bq/L can thus be obtained for both 99Tc and 129I. PMID- 1310305 TI - The Gamma Contamination Food Factor. AB - We suggest that radioactive food contamination, as determined solely by a quantitative gamma-ray spectroscopic measurement, may, apart from the total activity per unit mass, be for quick reference conveniently characterized by another single figure which we call the "Gamma Contamination Food Factor" (GCFF). This factor may be defined as the ratio of the total specific activity of gamma ray-emitting radionuclides in the food sample (except that of 40K) to the specific activity of 40K either in the sample itself or in an "average man". We discuss briefly the meaning and advantages of these definitions. PMID- 1310306 TI - The determination of dissolved radon in water supplies by the E-PERM system (electret ionization chamber). AB - Elevated levels of radon may be found in well waters and individuals who ingest such waters may receive significant radiation doses. This paper discusses the experience of the Radiation Protection Service in using the E-PERM system for measuring dissolved radon in water samples. PMID- 1310307 TI - The Ca2+ pump of the plasma membrane. PMID- 1310308 TI - Poly(A) removal is the kinase-regulated step in tumor necrosis factor mRNA decay. AB - Tumor necrosis factor (TNF) is a pleiotropic biomodulator and an important inducer of certain pathophysiologic immune reactions such as granuloma formation, cachexia, and septic shock. The production of TNF by astrocytes, which may figure prominently in the development of immune responses within the central nervous system, is subject to post-transcriptional regulation. We have previously shown that in virus-stimulated astrocytes, inhibition of protein kinase C results in a specific, 10-fold decrease in TNF mRNA half-life. Here we show that the decay of TNF messages induced in the macrophage-like cell line RAW 264.7 by either virus or lipopolysaccharide was subject to similar regulation, and that this pathway influenced the amount of TNF protein released by stimulated cells. Using a modified RNase protection assay, we demonstrate that inhibition of protein kinase C significantly enhanced the rate of poly(A) removal from TNF mRNA, thus facilitating an early event in the process of mRNA degradation. PMID- 1310309 TI - cAMP-dependent kinases in the algal flagellate Euglena gracilis. AB - Euglena cells grown in diurnal light-dark cycles exhibit circadian variations of their cAMP content, which we believe to be under the control of an endogenous timer because they persist in constant darkness in the absence of any environmental time cue. We think that these cAMP oscillations may play a role in the regulation of some of the numerous cellular activities that are known to display circadian rhythmicities in this organism. The role of cAMP in algal cells is still controversial, however, since the nature of the cAMP "receptor" is unknown. We show that extracts of the achlorophyllous ZC mutant of Euglena gracilis contain two cAMP-binding proteins, which bind cAMP with a high affinity (Kd values of 10 nM and 30 nM) and which can be separated by DEAE-cellulose chromatography. Protein kinase activity was assayed using Kemptide as a substrate. Stimulation of kinase activity by cAMP was observed after partial purification by DEAE-cellulose chromatography. Two peaks of activity were resolved, corresponding to distinct enzymes with different cAMP-analog specificities. Thus, cAMP signaling in plant cells may proceed by the phosphorylation of target proteins by cAMP-dependent kinases, in a manner similar to that of animal cells. PMID- 1310310 TI - Receptor-activated Ca2+ influx. Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells. AB - Receptor-activated Ca2+ influx was investigated in PC12 cells clones loaded with fura-2. Cells were stimulated in a Ca(2+)-free medium and studied after reintroduction of the cation or addition of Mn2+ into the medium. A first influx component, independent of receptor activation and sustained by depletion of the intracellular inositol 1,4,5-trisphosphate sensitive Ca2+ store (store-dependent Ca2+ influx, SDCI), was identified by experiments with carbachol followed by atropine and with agents that induce store discharge without polyphosphoinositide hydrolysis: thapsigargin, an inhibitor of Ca(2+)-ATPase activity; ryanodine and caffeine, activators of the ryanodine receptor. A second component of Ca2+ influx, induced by carbachol and rapidly blocked by atropine, relies on receptor effector coupling via G protein(s) different from that (those) involved in phospholipase C activation. SDCI and receptor-coupled influx are similar in their voltage dependence and insensitivity to forskolin and phorbol esters but they differ with respect to their Mn2+ permeability and their sensitivity to the SC 38249 imidazole blocker. The two components might play different roles. SDCI might act as a safety device to prevent Ca2+ store depletion whereas receptor dependent influx might control physiological functions such as secretion and growth. PMID- 1310311 TI - A unique fluorescent phenylalkylamine probe for L-type Ca2+ channels. Coupling of phenylalkylamine receptors to Ca2+ and dihydropyridine binding sites. AB - The first fluorescently labeled phenylalkylamine, DMBODIPY-PAA (5-(3-[3-(4,4 difluoro-5,7-dimethyl-3a, 4a-diaza-4-bora-indacen-3-yl)propionamido] phenethyl-N methylamino)-2-isopropyl-2-(3,4,5-trimethoxyphenyl)-valer onitrile) has been introduced for L-type Ca2+ channel research. DMBODIPY-PAA binds reversibly to L type Ca2+ channels purified from rabbit skeletal muscle microsomes by wheat germ agglutinin-Sepharose chromatography. In this preparation DMBODIPY-PAA labels 412 pmol of phenylalkylamine receptors/mg of protein with a Kd of 6.82 nM and a favorable signal-to-noise ratio. Therefore DMBODIPY-PAA has a higher affinity for purified Ca2+ channels than the commonly employed radioligands and consequently has assisted in channel purification after prelabeling by simply monitoring receptor-bound fluorescence. (+)-PN200-110 (which is stimulatory for (-) [3H]desmethoxyverapamil binding to purified Ca2+ channels) inhibits DMBODIPY-PAA labeling. Since these drug interactions are reciprocal, the phenylalkylamine and dihydropyridine binding sites of the alpha 1-subunit are tightly coupled. Kinetic and equilibrium binding studies with (-)-[3H]desmethoxyverapamil and DMBODIPY-PAA show that phenylalkylamine binding to L-type Ca2+ channels is dependent on Ca2+. Chelation of divalent metal ions converts phenylalkylamine receptors into a very low affinity state. This conversion is temperature- and time-dependent and completely reversible (K0.5 for free Ca2+ = 58 nM). This study demonstrates the utility of fluorescent ligands for binding studies with L-type Ca2+ channels and provides evidence for coupling between Ca2+ binding sites and phenylalkylamine receptors. PMID- 1310312 TI - Cloning, structural analysis, and expression of the glycogen phosphorylase-2 gene in Dictyostelium. AB - The glycogen phosphorylase-2 (GP2) activity that appears during the cell differentiation of Dictyostelium was purified to homogeneity. The molecular weight of the nondenatured enzyme was 200,000 as determined by Sephacryl S-300 gel filtration and was 107,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the native enzyme consists of two similar subunits. The intact protein was digested with trypsin and protease V8, and the resulting peptides were purified by microbore high pressure liquid chromatography. The peptides were sequenced, and oligonucleotides were constructed for polymerase chain reaction amplification of the GP2 gene from Dictyostelium genomic DNA template. The resulting polymerase chain reaction products were sequenced directly and were confirmed to encode portions of the GP2 gene. These fragments were used to probe a partial EcoRI genomic library for the remainder of the GP2 gene. The nucleotide sequence of the GP2-selected clones revealed an open reading frame of 2975 base pairs that was interrupted by two introns of 109 and 105 base pairs, respectively. The open reading frame encoded a protein of 992 amino acids with a calculated molecular mass of 112,500 Da and an isoelectric point of 6.4. An unusual sequence within the second exon of GP2, in which the triplet CAA was repeated 11 times, resulted in 11 in-frame glutamine residues of a possible 15 amino acids coded for by this region. The CAA repeat was transcribed, as shown by the sequence of cDNA. Comparison of the amino acid sequence of Dictyostelium GP2 to the phosphorylases from other organisms revealed that the Dictyostelium protein was 50 and 44% identical to yeast and rabbit muscle phosphorylases, respectively. Northern blot analysis showed that GP2 mRNA was absent in amebas and the early stages of development, reached a maximum level of expression at the slug stage, and then decreased in the terminal stages of development. Comparison of the mRNA expression with the appearance of GP2 enzyme protein and enzyme activity revealed that gp2 mRNA and a 113-kDa GP2 enzyme peptide were expressed concurrently at 10 h of development. However, enzyme activity did not appear until 18 h, coincident with a decrease in the level of the 113-kDa peptide and a corresponding increase in the amount of a 106-kDa GP2 peptide. Addition of cAMP to aggregation-competent cells in liquid culture resulted in the induction of GP2 mRNA, GP2 protein, and GP2 enzyme activity. PMID- 1310313 TI - Localized mutagenesis defines regions of the Bacillus thuringiensis delta endotoxin involved in toxicity and specificity. AB - Bacillus thuringiensis produces a variety of delta-endotoxins which bind to specific receptors in insect larval midguts. Following insertion into the membrane there is an alteration of ion flux culminating in osmotic lysis. Mutagenic oligonucleotides were used to define regions in one of these toxins involved in specificity and toxicity. One region is highly conserved among all toxins sequenced to date and many mutations resulted in loss of toxicity for three test Lepidoptera. The mutant toxins had lost the capacity to inhibit K(+) dependent amino acid transport into larval midgut vesicles, but there was no effect on their ability to compete with wild type toxin for binding. The results are consistent with this amphiphilic helical region of the toxin being essential for toxicity. A second mutagenized region overlapped a portion of another potential amphiphilic helix. Mutations of only 2 residues, Ala-92 and Arg-93, resulted in loss of toxicity for two lepidopteran larvae but some activity remained for a third. The A92D mutant toxin competed with the wild type toxin for binding to vesicles prepared from midguts from the sensitive but not from the insensitive larvae. Decreased toxicity was also found when this mutation was transferred to two other related protoxin genes. A number of mutations of each of these residues was analyzed and selective loss of toxicity correlated with the absence of a positive charge. Despite being distal from the presumptive specificity domain, 1 or both of these residues must have an important role in the specific binding of toxins. PMID- 1310314 TI - Dual mode of inhibition of purified DNA ligase I from human cells by 9-beta-D arabinofuranosyl-2-fluoroadenine triphosphate. AB - 9-beta-D-Arabinofuranosyl-2-fluoroadenine (F-ara-A) is an analogue of adenosine and deoxyadenosine with potent anti-tumor activity. The mechanism of action for this compound has been elucidated as the inhibition of DNA and RNA synthesis, induction of DNA fragmentation, and genetic damage. This study demonstrated that DNA ligase I, an enzyme involved in DNA replication, is a target for the drug action. F-ara-adenine triphosphate (F-ara-ATP) at 80 microM inhibited the activity of DNA ligase I by more than 90%. In contrast, eight other related nucleoside analogues showed no effect on the enzyme activity at 200 microM. F-ara ATP inhibited DNA ligation in two distinct ways. First, F-ara-ATP directly interacted with DNA ligase I and inhibited the formation of the ligase-AMP complex. This inhibition could not be reversed when free F-ara-ATP was eliminated from the treated enzyme; however, the addition of pyrophosphate, followed by gel filtration chromatography, restored enzyme activity, indicating that F-ara-ATP bound to the enzyme and altered the AMP-binding site. Secondly, the activity of DNA ligase I was inhibited when F-ara-ATP was incorporated into the 3' terminus of the DNA substrate. The dual mode of inhibition of DNA ligase I by F-ara-ATP indicates that its effect on DNA ligation may be important in the inhibition of DNA synthesis and the cytotoxicity of F-ara-A. PMID- 1310315 TI - Role of G protein beta gamma subunits in the regulation of the plasma membrane Ca2+ pump. AB - In Zajdela hepatoma cells (ZHC) the plasma membrane Ca2+ pump displayed no sensitivity to glucagon (19-29) (mini-glucagon), whereas in hepatocyte this metabolite of glucagon evoked a biphasic regulation of the Ca2+ pump system via a cholera toxin-sensitive G protein. Analysis of G protein subunits in ZHC membranes indicated the presence of cholera toxin-sensitive Gs alpha and G beta gamma proteins, whose functionality was manifested by GTP and NaF stimulation of adenylylcyclase activity, and pertussis toxin-catalyzed ADP-ribosylation of Gi alpha, respectively. However, immunoblotting experiments suggested a lower content in beta gamma subunits in ZHC as compared with hepatocyte plasma membranes. Complementation of ZHC or hepatocyte plasma membranes with purified beta gamma subunits from transducin (T beta gamma) caused inhibition of the basal activity of the Ca2+ pump at 10 and 300 ng/ml, respectively, and revealed (in ZHC) or increased (in hepatocytes) sensitivity of the system to mini-glucagon. After cholera toxin treatment of ZHC, T beta gamma no longer reconstituted the response of the Ca2+ pump to mini-glucagon, suggesting that the mechanism of beta gamma action is dependent on an association with the alpha subunit of a cholera toxin-sensitive G protein. It is concluded that G beta gamma subunits control both the basal activity of the plasma membrane Ca2+ pump and its inhibition by mini-glucagon. PMID- 1310316 TI - Purification and properties of a secreted and developmentally regulated alpha-L fucosidase from Dictyostelium discoideum. AB - During its development the eukaryotic microorganisms Dictyostelium discoideum secretes an alpha-L-fucosidase (EC 3.2.1.51). In cells of the growth phase almost no alpha-L-fucosidase activity is detectable. The activity increases steadily up to the aggregation stage and accumulates also in the extracellular medium. The developmental regulation is mediated by pulsatile cAMP signals. The alpha-L fucosidase was purified from extracellular medium. The isolation procedure started with concentration of the enzyme by batchwise anion-exchange chromatography and ammonium sulfate precipitation, followed by Sephacryl S-300 gel filtration and further purification by fast protein liquid chromatography on Mono Q, phenyl-Superose, and finally Superose 12. The purified preparation was found to be essentially free of activities of six other glycosidases also secreted by D. discoideum. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified enzyme showed one major band with an apparent molecular mass of 62 kilodalton. Gel filtration of the enzyme on a Superose 12 column was consistent with an active monomer. A monoclonal antibody was produced, which recognizes a carbohydrate epitope shared by all lysosomal enzymes in D. discoideum. The pH optimum of the alpha-L-fucosidase is at 3.7. The apparent Michaelis constant for p-nitrophenyl alpha-L-fucoside as substrate is 1.2 mM. The enzyme catalyzes preferentially the hydrolysis of alpha 1----6GlcNAc but also of alpha 1----2Gal and alpha 1----3Glc fucosyl linkages. PMID- 1310317 TI - The variant human isovaleryl-CoA dehydrogenase gene responsible for type II isovaleric acidemia determines an RNA splicing error, leading to the deletion of the entire second coding exon and the production of a truncated precursor protein that interacts poorly with mitochondrial import receptors. AB - Isovaleryl-CoA dehydrogenase (IVD) is a mitochondrial enzyme involved in leucine metabolism. Previous studies of fibroblasts from patients with isovaleric acidemia (IVA), an inherited defect in IVD, have revealed that IVD precursor protein produced by type II IVA cells is 3 kDa smaller than normal and is processed inefficiently to a mature form which is also 3 kDa smaller than normal. Using the polymerase chain reaction, we have identified a 90-base pair deletion encompassing bases 145-234 in type II IVD cDNA. This deletion is caused by an error in RNA splicing and predicts the in-frame deletion of 30 amino acids beginning with leucine 20 of the mature IVD. The rate of leader peptide cleavage by purified mitochondrial leader peptidases was similar for the variant and normal precursor IVDs expressed in vitro, and radiosequencing confirmed that both mature proteins contain identical amino termini. In vitro import studies showed that the efficiency of overall mitochondrial import of type II variant IVD precursor was approximately 30% of normal, as was its binding to the mitochondrial surface. Unlike its normal counterpart, the bound variant IVD precursor was readily released. These data suggest that binding of the variant protein to mitochondrial membrane receptors per se is hindered, resulting in the inefficient mitochondrial processing. PMID- 1310318 TI - Adenovirus E1A represses the cyclic AMP-induced transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in hepatoma cells. AB - Adenovirus infection of hepatoma cells inhibited transcription of the phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) gene and virtually eliminated transcription of a chimeric gene which contained the PEPCK promoter linked to the structural gene for chloramphenicol acetyltransferase (CAT). This effect is due to the viral protein E1A, since adenovirus containing a deletion in the E1A gene did not repress transcription from the PEPCK promoter. Both the 243R and 283R products of the E1A gene were effective. The conserved region 1 (CR-1) domain of E1A was required for this effect. Treatment of hepatoma cells with 8 bromo-cAMP or transfection with plasmids coding for the catalytic subunit of protein kinase A, CAAT/enhancer binding protein alpha (C/EBP), or Jun, all potent inducers of PEPCK gene transcription, did not relieve the inhibition caused by E1A. This inhibition does not appear to be mediated by major enhancer elements and in the PEPCK gene since transcription from the PEPCK promoter containing block mutations in binding domains for C/EBP and cAMP regulatory element binding protein (CREB) was also inhibited by E1A. Transcription of chimeric genes containing two copies each of the major cAMP response domains (CRE-1 and P-3) linked to a neutral promoter and fused to the CAT structural gene was stimulated by the catalytic subunit of protein kinase A, but this effect was totally inhibited by E1A. The strong repressive effect of E1A on PEPCK gene transcription seems to involve an interruption of an obligatory interaction between factors which bind to the cAMP response element in the PEPCK promoter and the TATA box. PMID- 1310319 TI - Antagonism of synaptosomal calcium channels by subtypes of omega-agatoxins. AB - Venom of the funnel web spider Agelenopsis aperta inhibits the binding of 125I omega-conotoxin GVIA (omega-CgTx) to calcium channels in chick brain synaptosomal membranes. Fractionation of the venom by liquid chromatography shows that this inhibitory activity is associated primarily with a diverse class of peptide toxins called omega-agatoxins (omega-Aga). Using binding inhibition as an assay, we purified and identified the novel, 76-amino acid toxin, omega-Aga-IIIA. Inhibition of 125I-omega-CgTx binding to chick synaptosomal membranes by omega Aga-IIIA and omega-Aga-IIA is correlated with block of potassium-stimulated 45Ca entry into synaptosomes; omega-Aga-IA neither inhibits 125I-omega-CgTx binding nor 45Ca entry under identical conditions. omega-Aga-IIA and omega-Aga-IIIA are 20-30-fold more potent than omega-CgTx as antagonists of synaptosomal calcium channels. However, whereas omega-CgTx completely blocks 45Ca entry into synaptosomes at saturating concentrations, the omega-agatoxins maximally block only 60-70% of 45Ca entry. Pretreatment of synaptosomes with omega-Aga-IIIA occludes block of 45Ca entry by omega-CgTx. The results indicate that, while the omega-agatoxins bind to the entire population of omega-CgTx-sensitive calcium channels in chick synaptosomal membranes, they exert only a partial block of 45Ca flux. Such block could occur via two distinct mechanisms. Toxin binding may alter the kinetics of a homogeneous population of channels, resulting in lower overall conductance upon depolarization. Alternatively, the omega-agatoxins may bind to two distinct channel subtypes, only one of which is blocked as a result of toxin occupation. PMID- 1310320 TI - A malaria invasion receptor, the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum recognizes the terminal Neu5Ac(alpha 2-3)Gal- sequences of glycophorin A. AB - Plasmodium falciparum malaria parasites invade human erythrocytes by means of a parasite receptor for erythrocytes, the 175-kD erythrocyte binding antigen (EBA 175). Similar to invasion efficiency, binding requires N-acetylneuraminic acid (Neu5Ac) on human erythrocytes, specifically the glycophorins. EBA-175 bound to erythrocytes with receptor-like specificity and was saturable. The specificity of EBA-175 binding was studied to determine if its binding is influenced either by simple electrostatic interaction with the negatively charged Neu5Ac (on the erythrocyte surface); or if Neu5Ac indirectly affected the conformation of an unknown ligand, or if Neu5Ac itself in specific linkage and carbohydrate composition was the primary ligand for EBA-175 as demonstrated for hemagglutinins of influenza viruses. Most Neu5Ac on human erythrocytes is linked to galactose by alpha 2-3 and alpha 2-6 linkages on glycophorin A. Soluble Neu5Ac by itself in solution did not competitively inhibit the binding of EBA-175 to erythrocytes, suggesting that linkage to an underlying sugar is required for binding in contrast to charge alone. Binding was competitively inhibited only by Neu5Ac(alpha 2-3)Gal-containing oligosaccharides. Similar oligosaccharides containing Neu5Ac(alpha 2-6)Gal-linkages had only slight inhibitory effects. Binding inhibition assays with modified sialic acids and other saccharides confirmed that oligosaccharide composition and linkage were primary factors for efficient binding. EBA-175 bound tightly enough to glycophorin A that the complex could be precipitated with an anti-glycophorin A monoclonal antibody. Selective cleavage of O-linked tetrasaccharides clustered at the NH2 terminus of glycophorin A markedly reduced binding in inhibition studies. We conclude that the Neu5Ac(a2,3)-Gal- determinant on O-linked tetrasaccharides of glycophorin A appear to be the preferential erythrocyte ligand for EBA-175. PMID- 1310321 TI - Targeted disruption of the ABP-120 gene leads to cells with altered motility. AB - The actin-binding protein ABP-120 has been proposed to play a role in cross linking F-actin filaments during pseudopod formation in motile Dictyostelium amebas. We have tested this hypothesis by analyzing the phenotype of mutant cell lines which do not produce ABP-120. Two different transformation vectors capable of targeted disruption of the ABP-120 gene locus have been constructed using a portion of an ABP-120 cDNA clone. Three independent cell lines with different disruption events have been obtained after transformation of amebas with these vectors. The disruption of the ABP-120 gene by vector sequences results in either the production of a small amount of truncated ABP-120 or no detectable protein at all. The phenotypes of two different clones lacking ABP-120, generated in strains AX3 and AX4, have been characterized and show identical results. ABP-120- cells tend to remain rounder before and after cAMP stimulation, and do not reextend pseudopods normally after rapid addition of cAMP. In addition, ABP-120- cells translocating in buffer exhibit defects in both the rate and extent of pseudopod formation. The amount of F-actin cross-linked into the cytoskeleton after cAMP stimulation of ABP-120- cells is reduced at times when ABP-120 has been shown to be incorporated into the cytoskeleton, and this correlates temporally with the absence of reextension of pseudopods after cAMP stimulation. The instantaneous velocity is significantly reduced both before and after cAMP stimulation in the ABP-120- cells, and the cells show decreased chemotactic efficiency compared to ABP-120+ controls. This phenotype is consistent with a role for ABP-120 in pseudopod extension by cross-linking actin filaments as proposed by the "cortical expansion model" (Condeelis, J., A. Bresnick, M. Demma, C. Dharmawardhane, R. Eddy, A. L. Hall, R. Sauterer, and V. Warren. 1990. Dev. Genet. 11:333-340). PMID- 1310322 TI - Transforming growth factor beta 1 is a powerful modulator of platelet-derived growth factor action in vascular smooth muscle cells. AB - We have studied the effect of transforming growth factor beta 1 (TGF-beta 1) on vascular smooth muscle cell (SMC) mitogenesis and expression of thrombospondin and other growth related genes. We found that TGF-beta 1 treatment of vascular SMC induced a prolonged increase in steady-state mRNA levels of thrombospondin as well as alpha 1 (IV) collagen. The increase began at approximately 2 h, peaked by 24 h, and remained considerably elevated 48 h after growth factor addition. There was a corresponding increase in thrombospondin protein as well as increased expression of several other secreted polypeptides. The increase in thrombospondin contrasted sharply with that observed for platelet-derived growth factor (PDGF) which induced a rapid and transient increase in thrombospondin mRNA level. Although TGF-beta 1 was able to directly enhance expression of thrombospondin as well as the growth-related genes c-fos and c-myc, and induced c-fos expression with identical kinetics as PDGF, it was unable to elicit [3H]thymidine incorporation into DNA in three independent smooth muscle cell strains. However, TGF-beta 1 was able to strongly increase the mitogenic response of SMC to PDGF. Addition of both TGF-beta 1 and PDGF to SMC also caused a synergistic increase in the expression of thrombospondin as well as c-myc. Interestingly, in one other smooth muscle cell strain, a weak and delayed mitogenic response to TGF-beta 1 alone was observed. Our results strongly suggest that induction of thrombospondin expression by TGF-beta 1 and by PDGF occurs by distinct mechanisms. In addition, that TGF-beta 1 can enhance PDGF-induced mitogenesis may be due to the ability of TGF-beta 1 to directly induce the expression of thrombospondin, c-fos, c-myc, and the PDGF beta-receptor. PMID- 1310323 TI - Parathyroid hormone stimulates protein kinase C but not adenylate cyclase in mouse epidermal keratinocytes. AB - Intact human parathyroid hormone, hPTH [1-84], and the hPTH [1-34] fragment stimulated membrane-associated protein kinase C (PKC) activity in immortalized (but still differentiation-competent) murine BALB/MK-2 skin keratinocytes. Unexpectedly, the hormone and its fragment did not stimulate adenylate cyclase. The failure of PTH to stimulate adenylate cyclase activity was not due to the lack of a functioning receptor-cyclase coupling mechanism because the cells were stimulated to synthesize cyclic adenosine monophosphate (cyclic AMP) by the beta adrenergic drug isoproterenol. Thus, skin keratinocytes seem to have an unconventional PTH receptor that is coupled to a PKC-activating mechanism but not to adenylate cyclase. These observations suggest that normal and neoplastic skin keratinocytes respond to the PTH-related peptide that they make and secrete. PMID- 1310324 TI - Identification of basic fibroblast growth factor sensitivity and receptor and ligand expression in human colon tumor cell lines. AB - Basic fibroblast growth factor (bFGF) has been shown to be mitogenic to many different eukaryotic cell lines of mesodermal and neuroectodermal origin. Addition of exogenous bFGF to the chemically defined media of five characterized human colon tumor cell lines, cultured in the absence of epidermal growth factor (EGF), resulted in stimulation of growth from 24% to 146% in four of five cell lines, as measured by a colorimetric MTT assay. A positive dose-response relationship was observed when colon cells were treated with bFGF concentrations from 1 pM to 1 nM. bFGF showed a cumulative effect with EGF in stimulating the proliferation of colon tumor cells. The growth-inhibitory effect of exogenous transforming growth factor-beta (TGF-beta) on these cells was abolished by bFGF. When colon tumor cells were examined on immunoblots with a fibroblast growth factor (FGF) receptor-specific antibody, bands were detected at apparent molecular weights of 131 and 145 kDa. Conditioned media and cell lysates from the same human colon tumor cell lines were immunoprecipitated with a bFGF-specific antibody. An immunoreactive band was detected that comigrated with authentic human recombinant bFGF (16 kDa). Furthermore, preabsorption of anti-bFGF antibody with authentic ligand blocked immunodetection of the 16 kDa band on immunoblots. Documentation of a bFGF response, receptor, and ligand expression in human colon tumor cell lines is novel, and may represent a more widespread role for FGF that extends to epithelial cells and tumors of endodermal germ layer origin. The expression of both ligand and receptors by these cells indicates that bFGF could be involved in their growth regulation at the autocrine level. PMID- 1310325 TI - Subtypes of betaglycan and of type I and type II transforming growth factor-beta (TGF-beta) receptors with different affinities for TGF-beta 1 and TGF-beta 2 are exhibited by human placental trophoblast cells. AB - Transforming growth factor-beta is likely to be an important factor controlling placental activities, including growth, differentiation, invasiveness, hormone production, and immunosuppression. We have used a chemical cross-linking technique with either 125I-TGF-beta 1 or 125I-TGF-beta 2 and bis(sulfosuccinimidyl) suberate (BS3) to characterize TGF-beta binding components on human placental cells in primary culture. Trophoblast-enriched primary cultures exhibited a predominant affinity-labelled complex characteristic of membrane-anchored betaglycan (formerly termed the Type III TGF-beta receptor) and relatively low levels of the Type I and Type II TGF-beta receptor complexes. The results from affinity labelling saturation and competition experiments with TGF beta 1 and TGF-beta 2 suggest the existence of two distinct subtypes of betaglycan: one subtype has a lower capacity and higher affinity, binds both TGF beta 1 and TGF-beta 2, yet has a preferential affinity for TGF-beta 2; the second subtype has a higher capacity and lower affinity and binds TGF-beta 1 exclusively. In contrast, mesenchymal cell-enriched placental primary cultures possessed only one subtype of the betaglycan component that binds the two TGF beta isoforms with similar affinities and capacities as observed on most cell lines. These experiments demonstrate that the betaglycan component which exhibits a higher affinity for TGF-beta 2 than for TGF-beta 1, that we had observed previously on term placental membranes, is actually present on trophoblast cells. In addition to the two distinctive betaglycan subtypes, subtypes of the Type I and II TGF-beta receptors were detected on the trophoblast-enriched cultures. In competition experiments, when 125I-TGF-beta 1 was used as the radiotracer, the Type I and II TGF-beta receptors show a much higher affinity for TGF-beta 1 than for TGF-beta 2, as observed with other cell types. However, when 125I-TGF-beta 2 was used, low abundance subtypes of both the Type I and II receptors that show similar affinities for TGF-beta 1 and TGF-beta 2 were also revealed. PMID- 1310326 TI - Differential induction of the c-fos promoter through distinct PDGF receptor mediated signaling pathways. AB - The multiple isoforms of PDGF induce fibroblastic mitogenesis through two distinct PDGF receptors, alpha and beta. The molecular mechanisms by which these alpha and beta PDGF receptors regulate gene expression are poorly understood. We present data which indicates that differential induction of c-fos gene expression by PDGF isoforms occurs through distinct PDGF alpha and beta receptor-mediated signaling pathways. Comparison of PDGF-AA with PDGF-BB stimulation showed that PDGF-BB induced prolonged expression of the c-fos gene in BALB/c-3T3 cells, but that PDGF-AA induced more potent activation of the serum response element (SRE) in transient transfection assays. PDGF-AA, which binds alpha but not beta PDGF receptors, could only induce the SRE through a protein kinase C (PKC)-dependent pathway, whereas PDGF-BB, which binds both alpha and beta PDGF receptors, could also induce the SRE through a PKC-independent pathway. These results suggest that PDGF alpha receptors activate the PKC-dependent signaling pathway while PDGF beta receptors also activate a PKC-independent pathway. In addition, we found that PDGF-BB could induce another c-fos promoter element within the -90 to +10 region, suggesting that the more potent mitogenic effect and prolonged c-fos gene expression induced by PDGF-BB may result from cooperativity between more than one c-fos promoter elements. PMID- 1310327 TI - Lipopolysaccharides decrease angiotensin converting enzyme activity expressed by cultured human endothelial cells. AB - Angiotensin converting enzyme (ACE) is present on endothelial cells and plays a role in regulating blood pressure in vivo by converting angiotensin I to angiotensin II and metabolizing bradykinin. Since ACE activity is decreased in vivo in sepsis, the ability of lipopolysaccharide (LPS) to suppress endothelial cell ACE activity was tested by culturing human umbilical vein endothelial cells (HUVEC) for 0-72 hr with or without LPS and then measuring ACE activity. ACE activity in intact HUVEC monolayers incubated with LPS (10 micrograms/ml) decreased markedly with time and was inhibited by 33%, 71%, and 76% after 24 hr, 48 hr, and 72 hr, respectively, when compared with control, untreated cells. The inhibitory effect of LPS was partially reversible upon removal of the LPS and further incubation in the absence of LPS. The LPS-induced decrease in ACE activity was dependent on the concentrations of LPS (IC50 = 15 ng/ml at 24 hr) and was detectable at LPS concentrations as low as 1 ng/ml. That LPS decreased the Vmax of ACE in the absence of cytotoxicity and without a change in Km suggests that LPS decreased the amount of ACE present on the HUVEC cell membrane. While some LPS serotypes (Escherichia coli 0111:B4 and 055:B5, S. minnesota) were more potent inhibitors of ACE activity than others (E. coli 026:B6 and S. marcescens), all LPS serotypes tested were inhibitory. These finding suggest that LPS decreases endothelial ACE activity in septic patients; in turn, this decrease in ACE activity may decrease angiotensin II production and bradykinin catabolism and thus play a role in the pathogenesis of septic shock. PMID- 1310328 TI - Detection of cytomegalovirus antibodies by an enzyme-linked immunosorbent assay using recombinant polypeptides of the large phosphorylated tegument protein pp150. AB - Parts of the large phosphorylated tegument protein, pp150, of human cytomegalovirus (HCMV) were expressed in bacteria. The resulting fusion proteins were tested in a Western blot (immunoblot) assay for reactivity with a monoclonal antibody against pp150, with a polyspecific rabbit antiserum, and with human reconvalescent-phase sera. Those fusion proteins that performed well in the Western blot assay were used as antigens in enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies against HCMV. Five different recombinant beta-galactosidase fusion proteins were evaluated by ELISA using 62 seropositive and 38 seronegative human serum samples. Of all the proteins tested, one peptide representing 162 amino acids of pp150 was superior to the others with regard to sensitivity and specificity. All sera known to be positive for antibodies against HCMV were identified by combining the results of the ELISAs with the different pp150 fusion proteins. Therefore, it appears that peptides from a single protein of HCMV might be sufficient to identify HCMV-seropositive individuals by recombinant ELISA. PMID- 1310329 TI - MIC quality control guidelines for Haemophilus susceptibility tests using cefdinir (FK482), cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin. AB - A multilaboratory study was performed to establish broth microdilution MIC quality control (QC) guidelines for 10 investigational drugs which previously demonstrated significant activity against Haemophilus influenzae. MIC QC ranges for H. influenzae ATCC 49247 with Haemophilus test medium were determined by using multiple contemporary lots of Haemophilus test medium and the National Committee for Clinical Laboratory Standards' recommended numbers of replicate tests. On the basis of these results, QC ranges (generally modal MIC +/- one log2 dilution) are proposed for cefdinir, cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin. The proposed QC guidelines for clarithromycin and temafloxacin were recently accepted by the National Committee for Clinical Laboratory Standards. PMID- 1310330 TI - Amplification of human papillomavirus type 16 transforming genes from cervical cancer biopsies and lymph nodes of Hungarian patients. AB - We have used a polymerase chain reaction (PCR) to examine cervical cancer biopsy specimens and pelvic lymph nodes for the presence of human papillomavirus type 16 (HPV 16) DNA. Of the 75 cervical specimens tested, 36 (48%) were positive for HPV 16 in the PCR. A total of 65 pelvic lymph nodes removed during radical surgery on 35 women were also analyzed. Lymph nodes originating from 19 patients whose cervical biopsy specimens were negative for HPV 16 seemed to lack HPV 16 sequences. For 16 women with positive PCR results for cervical biopsy specimens, 9 of 10 lymph node metastases were positive in the PCR, while 11 of their 36 histologically negative lymph nodes were also shown to contain HPV 16 DNA. PMID- 1310331 TI - Selective detection of Mycoplasma fermentans by polymerase chain reaction and by using a nucleotide sequence within the insertion sequence-like element. AB - A new assay using the polymerase chain reaction to amplify a 206-nucleotide specific gene sequence within the insertion sequence-like element of Mycoplasma fermentans has been developed. The unique insertion sequence-like element exists in multiple copies in the M. fermentans genome. The assay selectively amplifies DNA from all strains of M. fermentans tested. In contrast, DNA from other species of human and nonhuman mycoplasmas, common tissue culture-contaminating mycoplasmas, and bacteria, as well as human, monkey, and mouse tissues do not produce the amplified DNA products specific for M. fermentans. PMID- 1310332 TI - Susceptibility testing of clinical isolates of Enterococcus faecium and Enterococcus faecalis. AB - We collected 103 clinical Enterococcus faecium isolates from across Canada, performed standard broth microdilution susceptibility testing, and compared these results with results from the MicroScan Pos MIC Type 6 panel (Baxter Health Care Corp., West Sacramento, Calif.) and the AMS-Vitek Gram-Positive Susceptibility card (Vitek Inc., St. Louis, Mo.). High-level aminoglycoside resistance to gentamicin and streptomycin was detected by a single-concentration agar method with 1,000 micrograms of each aminoglycoside per ml. In addition, we tested the effect of the lower calcium content in broth media as recommended in National Committee for Clinical Laboratory Standards (NCCLS) guideline M7-A2 on the activity of the highly calcium-dependent agent daptomycin. Of the 103 E. faecium isolates, there were 4 and 30 isolates with high-level gentamicin resistance (HLGR) and high-level streptomycin resistance (HLSR), respectively. An additional 39 (37 with HLGR and 36 with HLSR) E. faecium isolates were tested by both the MicroScan and the AMS-Vitek systems. The AMS-Vitek card demonstrated sensitivities of 95 and 82% for detecting HLGR strains and HLSR strains, respectively. The MicroScan panel demonstrated improved sensitivities for detecting HLGR (42 to 97%) and HLSR (64 to 84%) when readings were performed manually instead of being generated automatically. Ampicillin resistance (MIC, greater than or equal to 16 micrograms/ml) was detected in 23 of the 103 E. faecium isolates. Only 14 and 20 of these were detected by the MicroScan panels and AMS-Vitek cards, respectively. beta-Lactamase activity was not detected in any isolates. The lower calcium content in broth media recommended by NCCLS guideline M7-A2 markedly reduced the in vitro activity of daptomycin against Enterococcus spp. PMID- 1310333 TI - Rotavirus serotype G3 predominates in horses. AB - Foal fecal group A rotavirus strains were characterized by electropherotype, serotype, and subgroup and shown to be distinctly different from rotaviruses of other mammals. Of 86 strains that were electropherotyped, 98% had similar profiles, with gene segments 3 and 4 close together and segments 7, 8, and 9 widely spaced. Of 70 strains that had sufficient detectable VP7 antigen to be serotyped by enzyme-linked immunosorbent assays (ELISAs), 63% were serotype G3 (39% were subtype G3A and 24% were subtype G3B), 4% were serotype G13, and 33% were untypeable. Serotypes G1, G2, G4, G5, G6, G9, G10, and G14 were not detected, although G5 and G14 strains have been identified among cultivable equine strains. Of 50 strains that had sufficient detectable VP6 antigen to be subgrouped by ELISAs, only 12% were able to be assigned to either subgroup I or II, with the remaining 88% belonging to neither subgroup. PMID- 1310334 TI - Isolation of an avianlike group A rotavirus from a calf with diarrhea. AB - An atypical group A rotavirus (993/83) was isolated from a 3-day-old German calf with diarrhea. It differed from 35 conventional German bovine rotavirus isolates analyzed previously with respect to subgroup (strain 993/83 was non-subgroup I and non-subgroup II), serotype (strain 993/83 showed a two-way cross-reaction with serotype 7 and a one-way cross-reaction with serotype 3), and electropherotype (strain 993/83 showed comigrating gene segments 10 and 11). Isolate 993/83 reacted with only one of four monoclonal antibodies that recognized a common VP6 epitope(s). In addition, VP6 and VP2 of isolate 993/83 showed one-dimensional peptide maps that differed substantially from the peptide maps of VP6 and VP2 from all bovine rotavirus isolates. By RNA-RNA hybridization, the 993/83 probe failed to react with a panel of mammalian rotavirus strains, including bovine rotaviruses. It hybridized, however, to genomic RNA of an avian rotavirus strain. Isolate 993/83 could thus represent a candidate for a natural interspecies transmission of rotavirus between different classes of vertebrates. PMID- 1310335 TI - Rapid detection and identification of avian infectious bronchitis virus. AB - A rapid and sensitive method for the detection and unambiguous typing of infectious bronchitis virus (IBV) is described. RNA was isolated from IBV infected allantoic fluid and was transcribed into cDNA. This cDNA was amplified by the polymerase chain reaction. The polymerase chain reaction products were subsequently analyzed on an agarose gel. The presence of IBV-specific RNA in the allantoic fluid then allowed the amplification of a 438-bp DNA fragment from the nucleocapsid (N) gene. For the typing of IBV isolates, we used amplified double stranded DNA as a template in a sequencing reaction. We report 360 bases of the N gene of 18 IBV isolates. The sequence of the N gene was different between serologically indistinguishable IBV strains and may be a valuable tool in epidemiologic studies. A phylogenetic tree that was based on the sequences obtained did not agree with trees that were based on other parts of the sequence, illustrating the high frequency of recombination between IBV strains. PMID- 1310337 TI - Glycoprotein glycosylation and the immunosuppressive effects of human pregnancy serum. AB - Pregnancy serum contains a factor or factors which suppress T lymphocyte proliferation, although the identity of the factor(s) is still unclear. We have demonstrated that the immunosuppressive activity of pregnancy sera can be destroyed by treatment with periodate which oxidises protein-linked oligosaccharides. Similar effects have been noted with uromodulin, a potent immunosuppressive glycoprotein initially isolated from pregnancy urine. We find, however, that uromodulin is present in both pregnancy and non-pregnancy sera, and that removal of uromodulin from pregnancy serum by lectin affinity chromatography is not associated with loss of activity, ruling out this glycoprotein as the immunosuppressive factor. The possible role of protein-linked oligosaccharides of other serum glycoproteins in causing the pregnancy-related immunosuppression is discussed. PMID- 1310338 TI - From the Alcohol, Drug Abuse, and Mental Health Administration. PMID- 1310339 TI - Thyrotropin-releasing hormone selectively reverses lorazepam-induced sedation but not slowing of saccadic eye movements. AB - To investigate preliminary reports that benzodiazepine-induced sedation may be reversed by thyrotropin-releasing hormone (TRH), we examined the effect of TRH or saline placebo on two variables which are sensitive to benzodiazepine agonists: changes in sedation and saccadic eye movements. Lorazepam 10 micrograms/kg i.v. increased self-ratings of sedation and reduced self-ratings of alertness and these changes were almost completely reversed by TRH. In contrast the slowing of saccadic eye movements by lorazepam was not reversed by TRH. The effects of TRH do not appear to be due to a direct antagonism at the benzodiazepine receptor, since flumazenil reverses changes in both variables. Moreover ligand binding studies reveal that TRH has very low affinity at this receptor. These clinical data provide the first demonstration that it is possible to distinguish between the effects of benzodiazepines on saccadic eye movements and psychological self ratings. PMID- 1310336 TI - Molecular and serological analyses of two bovine rotaviruses (B-11 and B-60) causing calf scours in Australia. AB - Fecal specimens from 78 calves involved in outbreaks of calf diarrhea which occurred in three farms in Victoria, Australia, in 1988 were analyzed for rotaviruses. Thirty-eight samples were positive for group A virus antigen by enzyme-linked immunosorbent assay, and 20 of these contained viral double stranded RNAs that could be detected by polyacrylamide gel electrophoresis. Two major electropherotypes could be observed, and a representative isolate of each electropherotype (isolates B-11 and B-60) was successfully adapted to grow in MA104 cells. Sequencing of the VP7 genes directly from RNA transcripts of fecal and cell culture-adapted viruses demonstrated that no base changes occurred in this gene upon adaptation to growth in MA104 cells. Sequencing also revealed that the VP7 protein of B-60 was closely related to G serotype 6 (G6) strains, whereas the B-11 sequence was significantly different from all previously published sequences except the recently reported VP7 sequences of bovine isolates 61A and B223, particularly across the antigenic regions A, B, and C. The other strains most closely related to B-11 by VP7 amino acid sequence analysis were G4 porcine strains BMI-1 and BEN-144 and G8 human strain 69M. Serotyping of B-11 and B-60 gave results that were in good agreement with the sequencing data. Hyperimmune typing sera clearly identified B-60 as a member of G6, whereas the B-11 strain reacted to moderate titers only with antisera to some G10 strains. Antiserum raised against B-11 neutralized some strains of G10 cross-reacted with porcine G4 type isolates BMI-1 and BEN-144 but not with other G4 strains or with rotaviruses of other mammalian G serotypes. Northern blot hybridization showed that B-11 was closely related to the recently reported bovine G10 strain B223, and they both possessed a similar segment 4 that was different from that of either UK bovine or NCDV rotavirus. PMID- 1310340 TI - U-54494A reduces 4-AP-induced afterdischarges of CA1 pyramidal cells in the hippocampal slice of the rat. AB - The anticonvulsant activity of U-54494A was studied in a 4-aminopyridine (4-AP) epilepsy model using extracellular recordings in in vitro hippocampal slices. Field potentials were evoked by stimulation of Schaffer collaterals, and recorded from the CA1 region of the hippocampus after infusion of 4-AP in the absence and presence of U-54494A. The number and the total area of after discharges (AD) in the presence of 4-AP were significantly decreased by increasing concentrations of U-54494A. In contrast, U-54494A did not significantly change the latency, duration, or area of the evoked PS in this paradigm. Phenytoin, a standard anticonvulsant, decreased the PS area without affecting either the PS latency or duration, or the AD number or area in the same paradigm. These present results provide more evidence that U-54494A is a novel and effective anticonvulsant that may be useful in the treatment of paroxysmal activity, without having generalized depressive effects. PMID- 1310342 TI - Management of women with HPV change on Pap smears. PMID- 1310341 TI - In vivo sodium chemical shift imaging. AB - The shift reagents thulium(III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'tetramethylenephosphonate (TmDOTP5-), and dysprosium(III)triethylenetetramine-hexaacetate (DyTTHA3-) are compared in this work for their uses in sodium chemical shift imaging (NaCSI). In a series of experiments using phantoms we evaluated the relative contributions of bulk magnetic susceptibility (BMS) effects and hyperfine shifts to the induced 23Na chemical shift for these two shift reagents. The ratios of BMS effects to hyperfine shifts suggest that TmDOTP5- should be a more effective shift reagent than DyTTHA3- for 23Na NMR spectroscopy as well as NaCSI. The dependence on pH and free Ca2+ concentration of the 23Na NMR frequency shift induced by TmDOTP5- was evaluated. It was found that TmDOTP5- produces good spectral resolution under physiologic conditions. Examples presented from in vivo NaCSI experiments using TmDOTP5- to study diffusion in the posterior chamber of the rabbit eye and to monitor the rate of clearance of aqueous fluid from the anterior chamber demonstrate the effectiveness of this new shift reagent and of the NaCSI technique for in vivo studies. PMID- 1310343 TI - Inflammatory pseudotumor of the liver masquerading as a metastasis in a child treated for nephroblastoma. AB - A 3 1/2-year-old boy presented with a palpable hepatic tumor thought on clinical and radiological grounds to be a metastasis but which was found to be an inflammatory pseudotumor on histological examination. Eighteen months previously he had received chemotherapy and radiotherapy for a stage IV Wilms' tumor, which had been surgically excised 4 months after commencing treatment. This case illustrates the importance of obtaining a histological diagnosis in the management of patients with malignant tumors. PMID- 1310344 TI - Chemotherapy with actinomycin D influences the growth of the spine following abdominal irradiation. PMID- 1310345 TI - Extrapulmonary and pulmonary small-cell carcinoma: tumor biology, therapy, and outcome. AB - Extrapulmonary small-cell cancer is a distinct clinicopathological entity from small-cell anaplastic carcinoma of the lung. Approximately 1,000 cases have been projected annually in the United States, which represents an overall incidence of between 0.1% and 0.4% of all cancer. Not surprisingly then, little information is available regarding the treatment of this disease, which presents a challenge to the clinician when it is regionally confined. The majority of patients with extrapulmonary small-cell neoplasms have only been treated with local modalities of therapy, surgery, radiation, or a combination of both. Prolonged survival is not infrequent, which is in contrast to the experience for small-cell lung cancer and surprising given our current systemic approach to patients with this disease. This report will summarize the similarities and differences in biology, natural history, and clinical characteristics of patients with extrapulmonary small-cell cancer and small-cell anaplastic carcinoma of the lung. The histogenesis of small cell cancer is briefly reviewed. A general therapeutic approach to patients with small-cell lung cancer is reported. Lastly, recommendations for therapy of patients with regionally confined extrapulmonary small-cell cancer by primary site are outlined. PMID- 1310346 TI - Screening indices for cytomegalovirus retinitis in patients with human immunodeficiency virus. AB - Cytomegalovirus retinitis, the major cause of blindness in patients with the acquired immunodeficiency syndrome, can be arrested by early detection and treatment. We identified 9 screening indices for early CMV retinitis: T-4/T-8 ratio less than 0.11, T-4 count less than 30, T-8 count less than 500, leukocytes less than 4,200, platelets less than 240,000, hemoglobin less than 11.6, hematocrit less than 35, less than 6 for a diagnostic profile which incorporates these 7 indices, and less than 2 for the IA-sum which compounds T-cell inversion and anemia. A threshold value was determined for each index, identified by retrospective review of charts of 15 patients with CMV retinitis and 30 without. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curve area was calculated. The best screening index was the T-cell ratio, which had the highest sensitivity (0.93), negative predictive value (0.94-0.99) and receiver operating characteristic curve area (0.89), and a positive predictive value among the highest (0.50-0.82). PMID- 1310347 TI - Familial adenomatous polyposis: case report and review of extracolonic manifestations. AB - FAP, if left untreated, results in colorectal cancer. Appropriate early surgical intervention is of utmost importance. With the reduction in mortality from colorectal carcinoma, an increasing number of patients with FAP need lifelong follow-up to screen for extracolonic manifestations. Today, the major causes of death in patients with FAP who are cured of colorectal cancer, or have had a colectomy before its development, are desmoid tumors and periampullary carcinomas. In family members at risk, screening with flexible sigmoidoscopy should be initiated in adolescence; symptoms of diarrhea and rectal bleeding would warrant an even earlier examination. The upper gastrointestinal tract should be assessed endoscopically at the time the diagnosis of FAP is made. If any polyps are detected, a biopsy is essential. If no gastric or duodenal polyps are found, repeated examinations at 3-5 year intervals probably suffice in asymptomatic patients. Surgically, colectomy will be necessary. It is usually deferred until late adolescence, when it is thought that the patient will be mature enough to handle the emotional aspects of the operation as well as the possible future morbidity due to the procedure. The presence or absence of rectal polyps as well as the site and depth of any invasive rectal carcinoma will determine the appropriate surgical procedure. Alternatives must be well understood by the physician and discussed carefully with the patient preoperatively. PMID- 1310348 TI - Immune responses in the post-polio syndrome. PMID- 1310349 TI - Psychological stress and the common cold. PMID- 1310350 TI - Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. AB - Thyroid hormones and retinoic acid function through nuclear receptors that belong to the steroid/thyroid-hormone receptor superfamily. Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) require auxiliary nuclear proteins for efficient DNA binding. Here we report that retinoid X receptors RXR alpha is one of these nuclear proteins. RXR alpha interacts both with TRs and with RARs, forming heterodimers in solution that strongly interact with a variety of T3/retinoic acid response elements. Transfection experiments show that RXR alpha can greatly enhance the transcriptional activity of TR and RAR at low retinoic acid concentrations that do not significantly activate RXR alpha itself. Thus, RXR alpha enhances the transcriptional activity of other receptors and its own ligand sensitivity by heterodimer formation. Our studies reveal a new subclass of receptors and a regulatory pathway controlling nuclear receptor activities by heterodimer formation. PMID- 1310352 TI - The 10 P's: a mnemonic helpful in characterization and differential diagnosis of peripheral neuropathy. PMID- 1310353 TI - Clinical outcome in aggressively treated meningeal gliomatosis. AB - We reviewed 11 consecutive patients with an antemortem cytologic diagnosis of meningeal gliomatosis. In three patients, meningeal gliomatosis was diagnosed before surgical resection of the glioma. Three of five patients with anaplastic astrocytoma and one with oligodendroglioma improved with treatment. Patients with glioblastoma multiforme did not respond and had a median survival from the diagnosis of meningeal gliomatosis of only 8 weeks. Meningeal gliomatosis can be an early finding in gliomas. Treatment response is probably related to tumor histology and grade. PMID- 1310351 TI - Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. AB - Cellular responsiveness to retinoic acid and its metabolites is conferred through two structurally and pharmacologically distinct families of receptors: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). Here we report that the transcriptional activity of RAR and RXR can be reciprocally modulated by direct interactions between the two proteins. RAR and RXR have a high degree of cooperativity in binding to target DNA, consistent with previous reports indicating that the binding of either RAR or RXR to their cognate response elements is enhanced by factors present in nuclear extracts. RXR also interacts directly with and enhances the binding of nuclear receptors conferring responsiveness to vitamin D3 and thyroid hormone T3; the DNA-binding activities of these receptors are also stimulated by the presence of nuclear extracts. Together these data indicate that RXR has a central role in multiple hormonal signalling pathways. PMID- 1310354 TI - [Cell surface adhesion molecules: structure, function, clinical aspects]. AB - Intercellular and cell-matrix interactions play a crucial role in several physiological and pathological processes. These relationships are based on different cell adhesion molecules. Although adhesion receptors exhibit structural diversity, cell adhesion mechanisms are basically similar to each other. Details of receptor functions (e.g. the exact mechanisms of signal transduction) is poorly understood. In this paper authors summarize data on different cell adhesion antigens and also describe a few important biological features to collect more data on the complex interactions of these molecules. PMID- 1310355 TI - Varicella vaccine reflux. PMID- 1310356 TI - [Malignant hyperthermia]. AB - Malignant hyperthermia (MH) is a life threatening complication following anaesthesia with potent inhalational agents and suxamethonium. The signs of MH are caused by increased metabolism and secondary stimulation of the sympathetic nervous system due to uncontrolled, high intracellular concentrations of calcium in skeletal muscle. The hyperthermia is secondary to the increased energy turnover. Calcium release from the sarcoplasmic reticulum is increased due to a low threshold for release and prolonged opening of the calcium channel upon normal stimulation. The gene encoding the calcium channel is localized on chromosome 19 in humans, and a substitution of cysteine for arginine has recently been described in one family with MH. PMID- 1310357 TI - Free radical formation in single crystals of 2'-deoxyguanosine 5'-monophosphate tetrahydrate disodium salt: an EPR/ENDOR study. AB - Single crystals of 2'-deoxyguanosine 5'-monophosphate were X-irradiated at 10 K and at 65 K, receiving doses between 4.5 and 200 kGy, and studied using K-band EPR, ENDOR, and field-swept ENDOR (FSE) spectroscopy. Evidence for five base centered and more than nine sugar-centered radicals was found at 10 K following high radiation doses. The base-centered radicals were the charged anion, the N10 deprotonated cation, the C8 H-addition radical, a C5 H-addition radical, and finally a stable radical so far unidentified but with parameters similar to those expected for the charged cation. The sugar-centered radicals were the H abstraction radicals centered at C1', C2', C3', and C5', an alkoxy radical centered at O3', a C5'-centered radical in which the C5'-O5' phosphoester bond appears to be ruptured, a radical tentatively assigned to a C4'-centered radical involving a sugar-ring opening, as well as several additional unidentified sugar radicals. Most radicals were formed regardless of radiation doses. All radicals formed following low doses (4.5-9 kGy) were also observed subsequent to high doses (100-200 kGy). The relative amount of some of the radicals was dose dependent, with base radicals dominating at low doses, and a larger relative yield of sugar radicals at high doses. Above 200 K a transformation from a sugar radical into a base radical occurred. Few other radical transformations were observed. In the discussion of primary radicals fromed in DNA, the presence of sugar-centered radicals has been dismissed since they are not apparent in the EPR spectra. The present data illustrate how radicals barely traceable in the EPR spectra may be identified due to strong ENDOR resonances. Also, the observation of a stable radical with parameters similar to those expected for the charge guanine cation is interesting with regard to the nature of the primary radicals stabilized in X-irradiated DNA. PMID- 1310358 TI - Infiltrating neutrophils differ from circulating neutrophils when stimulated with C5a, NAP-1/IL-8, LTB4 and FMLP. AB - In this study we report on functional characteristics of pustule as well as blood polymorphonuclear neutrophils (PMN) in a patient suffering from relapsing bullous staphyloderma. Large numbers of viable PMN from newly formed pustules as well as from the peripheral blood were investigated. During the course of disease chemotactic migration, enzyme degranulation, superoxide-anion generation and leukotriene B4 production were determined simultaneously. The results revealed C5a- and NAP-1/IL-8-specific dysfunction of pustule PMN as compared with blood PMN. In contrast, FMLP-elicited functional activities of pustule PMN were only slightly affected. Our findings provide evidence that in inflamed tissue invading PMN are regulated by in situ generated mediators. C5a produced by staph, aureus induced activation of the alternative pathway of the complement cascade represents a predominant regulatory factor in situ. Furthermore, the results substantiate previous observations concerning different modulation of C5a and f met-peptide receptors on human PMN. PMID- 1310359 TI - Potocytosis: sequestration and transport of small molecules by caveolae. PMID- 1310360 TI - Superantigens and endogenous retroviruses: a confluence of puzzles. PMID- 1310361 TI - Polymerase II promoter activation: closed complex formation and ATP-driven start site opening. AB - Studies on bacterial RNA polymerases have divided the initiation pathway into three steps, namely (i) promoter binding to form the closed complex; (ii) DNA melting to form an open complex, and (iii) messenger RNA initiation. Potassium permanganate was used to detect DNA melting by mammalian RNA polymerase II in vitro. Closed complexes formed in a rate-limiting step that was stimulated by the activator GAL4-VP16. Adenosine triphosphate was then hydrolyzed to rapidly melt the DNA within the closed complex to form an open complex. Addition of nucleoside triphosphates resulted in the melted bubble moving away from the start site, completing initiation. PMID- 1310363 TI - Neurofibromatosis in infantile autism and other types of childhood psychoses. AB - Recent findings have suggested that the simultaneous occurrence of neurofibromatosis and childhood psychosis might be more than a coincidence. In this study of 341 children with infantile autism and other types of childhood psychosis seen as inpatients in two university clinics of child psychiatry in a 25-year period, only one case (0.3%) of concomitant occurrence of the disorders was found, which is a frequency no higher than expected by chance. PMID- 1310364 TI - Excessive life changes during childhood and their effects on mental and physical health in adulthood. AB - To evaluate the long-lasting effects of excessive life changes during childhood, a group of children sent during the war years 1939-1945 from Finland to Sweden was examined. Their physical and mental health were compared with those of a control group. Information was gathered by postal questionnaire and from various official records both in Finland and Sweden. A clinical interview enhanced the findings of the study. The groups did not differ greatly from each other. Somatically the control group suffered from chronic illnesses more than the group of war children. This particularly applied to cardiovascular diseases; the control group also received more medication free of charge, i.e. medication for chronic diseases, the expenses of which are covered by Public Health Care. As regards mental illnesses the groups were similar. The group of war children was more capable than the control group at recognizing and expressing their feelings. PMID- 1310362 TI - Seroepidemiology of viral infections among intravenous drug users in northern California. AB - Intravenous drug users are frequently exposed to parenterally transmitted viral infections, and these infections can spread to the general population through sexual activity. We investigated the prevalence of serologic markers for human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotropic virus type I/II (HTLV-I/II), hepatitis B virus (HBV), and hepatitis C virus (HCV) in intravenous drug users and their sexual contacts. Of 585 drug users from northern California tested for these serologic markers, 72% were reactive for the antibody to HCV, 71% for the antibody to hepatitis B core antigen, 12% for HTLV-I/II antibodies, and 1% for the HIV-1 antibody. The prevalence of serologic markers for these four viruses correlated with the duration of intravenous drug use, the ethnic group, and the drug of choice. More than 85% of subjects infected with either HCV or HBV were coinfected with the other virus. All persons reactive to HTLV-I/II antibodies had antibodies for either HBV or HCV. Of 81 sexual contacts tested, 17% had evidence of HBV infection while only 6% were reactive for HTLV-I/II antibodies and 4% for the antibody to HCV. None of this group was infected with HIV-1. We conclude that HTLV-I/II and HCV are inefficiently transmitted to sexual contacts while HBV is spread more readily. Programs designed to discourage the sharing of drug paraphernalia, such as needle and syringe exchanges, should decrease the risk of parenterally spread viral infections in intravenous drug users and thus slow the spread of these infections to the general population. PMID- 1310365 TI - Birth order, development and personality. AB - First borns tend to be different, some of the time, than children born into the other birth orders. This seems due to parental treatment. Parents are often overly anxious about their first child, and may be more restrictive with the first child than with later children. It may be that this is especially true if the first child is female, given the tendency of parents to be more protective of females than of males. Also, the first child has more time alone with the parents than subsequent children, by virtue of having no siblings until the second child is born. From the above factors, it appears that first borns grow up more fearful than later born children but also more intellectually oriented. These are only tendencies and would not be absolutely true in every instance. But, the birth order does seem to initiate a tendency for things to be as stated. As a result, first borns achieve much more than the other birth orders, perhaps due to early adult-oriented styles learned when they had only the parents and no other siblings. If this speculation is correct, the same finding should hold for only children as well. The greater anxiety, achievement, and creativity of some first borns means their lives may be very different as a result of having been the first born child in the family. PMID- 1310366 TI - School refusal in Japan. AB - In Japan, school refusal began to attract the attention of psychiatrists from about 1960, and has been one of the main focuses of contemporary child and adolescent psychiatry because of the increase in the number of patients. It is now one of the most popular diagnosis in the clinical practice of child and adolescent psychiatry in this country. School refusal, however, is not listed as a diagnostic classification of a syndrome or disease in such international classifications of psychiatry as the ICD-9, ICD-10 draft, DSM-III, or DSM-III-R. It is an important task for child and adolescent psychiatry in Japan to determine the position of school refusal in relation to the international diagnostic standards. In this paper, (1) We described the actual conditions of school refusal in Japan. (2) We argued that it was reasonable and clinically useful to retain the concept of school refusal as a clinical entity unique to Japan. PMID- 1310367 TI - The Finnish family competence study. Childbearing attitudes in pregnant nulliparae. AB - In this paper, the childbearing and childrearing attitudes of 1,443 primigravid women are characterized in relation to their level of knowledge of childbirth. Mothers with little childbirth knowledge needed extra support in the transition to parenthood. Their attitude toward pregnancy was more negative and they were less interested in obtaining childbirth information. The level of childbirth knowledge was measured by means of a questionnaire during the mother's first visit to the maternity health care clinic. The knowledge had some prognostic value in identifying the mothers who acutely needed support in coping with the experiences of pregnancy and in the transition to parenthood. PMID- 1310368 TI - Hopelessness in children and adolescents. An overview. AB - Most research on hopelessness has focused on adult populations. However, with the recent publication of Kazdin's Hopelessness Scale for Children, there has been increasing attention directed toward hopelessness in children. This report reviews research on hopelessness, and in both adults and children, emphasizes findings which support Beck's cognitive trial view of depression. Also discussed is the neglected topic of hopelessness within the academic setting, including attributions, motivation and delayed gratification. This report suggests ways to prevent and treat hopelessness in the school-aged child, focusing primarily on cognitive-behavioral techniques. PMID- 1310369 TI - Interferences in psychosocial development of seriously health-impaired and physically disabled children. Educational implications. AB - Improvements in neonatal care and medical intervention have dramatically increased the number of seriously health-impaired and physically disabled children who now survive to enroll in elementary and secondary schools. Investigation into the post-secondary status of those populations reveals that few of them are employed or living independently. Some researchers have recently found that the disappointing status of these individuals correlates more significantly with psychosocial factors than with intelligence or severity of the disability. This paper describes the circumstances which typically surround children with serious chronic illness or physical disability in the context of Erikson's stages of psychosocial development and suggests strategies for educators regarding the social development of such individuals during the elementary and secondary school years. PMID- 1310370 TI - Psychological aspects of precocious puberty. An overview. AB - During the last three decades the psychological consequences of precocious puberty have received considerable attention. The nature and shortcomings of relevant studies are described. It is emphasized that specialized counselling and guidance of families with children who have to cope with precocious puberty is important, since it often contributes to an appropriate behaviour adjustment without the development of psychiatric symptomatology. Guidelines for medical service and psychological management are provided. PMID- 1310371 TI - Down's syndrome and infant gaze. Gaze behavior of Down's syndrome and nondelayed infants in interactions with their mothers. AB - The study reported here compared the gaze behavior of infants with Down syndrome (DS) and nondelayed infants during interactions with their mothers. The subjects were 10 DS infants and 11 nondelayed infants. Five of the DS infants and 6 of the nondelayed infants were 4 months old; the rest were 9 months old. The results support the expectation that infants with DS gazed at their mothers longer than did nondelayed infants during face-to-face play, and also indicate that all the infants visually attended to their mothers less at 9 months than at 4 months of age. It is conjectured that the increased gaze of the infants with DS may well facilitate attachment in the 1st year of life. PMID- 1310372 TI - Sexual differentiation in children's drawings of pregnancy. AB - An analysis is reported of drawings of pregnancy by children of both sexes, with the hypothesis that it would be possible to determine sex-related characteristics of the drawings. Clear sexual differentiation in male and female children's representations of pregnancy was revealed by to features: the location of the baby inside the body of the mother and the tendency in some of the boys to "masculinize" the figure, of the expectant mother. PMID- 1310373 TI - Body composition of rural Beninese women in different seasons assessed by skinfold thickness and bioelectrical-impedance measurements and by a deuterium oxide dilution technique. AB - Body composition of 24 rural Beninese women was assessed in a pre- and a postharvest season by using skinfold-thickness measurements, bioelectrical impedance analysis (BIA), and deuterium oxide (D2O) dilution. Fat mass assessed by D2O dilution was 12.3 +/- 3.3 kg; by skinfold-thickness measurements, 13.8 +/- 3.3 kg; and by BIA, 14.1 +/- 2.9 kg. Fat mass assessed by D2O was significantly lower (P less than 0.05) than fat mass assessed by the other two methods. Body weight in the postharvest season was 0.8 +/- 1.6 kg higher (P less than 0.05) than during the preharvest season. All three methods demonstrated that there were no significant changes in fat mass but that fat-free mass increased significantly (P less than 0.05) from pre- to postharvest season. PMID- 1310374 TI - Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects. AB - Thirty healthy male subjects were randomly allocated into one of two treatment groups: group H subjects were maintained on a high-linoleic acid (LA) diet with the saturated fatty acids kept low and those in group L were kept on a low-LA, low saturate diet. After a 3-wk run-in period, subjects consumed a fish-oil supplement containing 1.6 g eicosapentaenoic acid (EPA)/d and 0.32 g docosahexaenoic acid as triglycerides for a further 4 wk. The diets alone resulted in a significant change in neutrophil phospholipid LA (H = 12.7 +/- 2.9%, L = 9.0 +/- 0.9%; P less than 0.05). Dietary supplementation with fish oil resulted in a significant increase in EPA in neutrophil phospholipids that was greater in group L (mean 2.0 +/- 0.4%) than group H (mean 1.5 +/- 0.3%; P less than 0.005). Reductions in arachidonic acid concentrations in neutrophil membranes were not different, nor could differences in leukotriene B4 production be detected. Our study indicates that the ingestion of n-6 fatty acids within the diet is an important determinant of EPA incorporation into neutrophil membranes. PMID- 1310375 TI - Physical properties of dietary fiber that influence physiological function: a model for polymers along the gastrointestinal tract. AB - The quantitative measurement of dietary fiber does not recognize its diverse actions on nutrient absorption, sterol metabolism, fermentation in the colon, and stool weight. These differences in action are more likely due to differences in physical characteristics along the gastrointestinal tract. This paper explores such physical characteristics and attempts to classify dietary fiber in a more physical manner. This approach recognizes the diverse and variant action of each dietary fiber, which may be modified as a result of processing and cooking without changing in any way the quantitative measurement of dietary fiber. The general principles developed in this paper could also be applied to other polymeric materials passing along the gastrointestinal tract. PMID- 1310377 TI - Do silica and asbestos cause lung cancer? PMID- 1310378 TI - Characterization of the fetal inflammatory response to cytomegalovirus placentitis. An immunohistochemical study. AB - The histopathologic features of cytomegalovirus placentitis, an established cause of chronic villitis, are well documented. However, the immunologic features of the fetal inflammatory response to placental cytomegalovirus infection are largely unknown. The characterization of the fetal-derived inflammatory cell reaction may be important in our understanding of both the intrauterine as well as the antenatal immunological response of the neonate to this important viral infection. We examined formalin-fixed placentas from four cases of confirmed congenital cytomegalovirus infection using an in situ DNA probe to cytomegalovirus, and a variety of antibodies to leukocyte antigens, including anti-CD68, CD45RO, CDw75, CD74, IgG, IgM, and IgA. All four placentas showed marked hyperplasia of fetal-derived placental macrophages, termed Hofbauer cells. A lymphocytic villitis was present in all placentas, which was characterized by positive staining in all cases with T-cell antibodies. There was no evidence of positive staining of lymphocytes using B-cell antibodies in any of the cases. Two placentas showed plasmacellular villitis, which stained positively for both IgG- and IgM-secreting cells, that was present as early as the second trimester of gestation. No IgA positivity of plasma cells was observed. These data are presented in light of current theories of fetal viral immunity. PMID- 1310376 TI - Detection of DNA sequence polymorphisms in human genomic DNA by using denaturing gradient gel blots. AB - Denaturing gradient gel electrophoresis can detect sequence differences outside restriction-enzyme recognition sites. DNA sequence polymorphisms can be detected as restriction-fragment melting polymorphisms (RFMPs) in genomic DNA by using blots made from denaturing gradient gels. In contrast to the use of Southern blots to find sequence differences, denaturing gradient gel blots can detect differences almost anywhere, not just at 4-6-bp restriction-enzyme recognition sites. Human genomic DNA was digested with one of several randomly selected 4-bp recognition-site restriction enzymes, electrophoresed in denaturing gradient gels, and transferred to nylon membranes. The blots were hybridized with radioactive probes prepared from the factor VIII, type II collagen, insulin receptor, beta 2-adrenergic receptor, and 21-hydroxylase genes; in unrelated individuals, several RFMPs were found in fragments from every locus tested. No restriction map or sequence information was used to detect RFMPs. RFMPs can be used as genetic markers, because their alleles segregate in a Mendelian manner. Unlike most other methods for detecting DNA sequence polymorphisms, a genomic DNA blot made from one gel can be hybridized consecutively with many (30 or more) different probes. PMID- 1310379 TI - Adenomyoepithelioma of the breast. A report of two cases. AB - We describe two cases of adenomyoepithelioma of the breast. The two tumors reported herein were well-circumscribed lesions that showed ducts lined by inner epithelial and outer myoepithelial cells and solid areas made up of fasciculated spindle myoepithelial cells. This dual differentiation was corroborated by immunohistochemical studies and electron microscopy. PMID- 1310380 TI - An ultrastructural comparison of sinusoids in hepatocellular carcinoma, adenomatous hyperplasia, and fetal liver. AB - Transmission and scanning electron microscopic examinations were performed to evaluate the fine-structural differences in sinusoids of hepatocellular carcinoma, adenomatous hyperplasia of the liver, and fetal livers. In cancerous sinusoids, thickened endothelial cells with loss of sieve plates were conspicuous features. In the sinusoids of adenomatous hyperplasia, scanning electron microscopy showed apparent sieve plates, and basement membrane formation (capillarization) was less conspicuous than in carcinoma. In fetal livers, occasional large gaps as well as small fenestrations in the endothelium were noted. Basement membrane materials were not seen. It was concluded that the sinusoids of hepatocellular carcinoma lost the fine-structural nature of normal sinusoids and showed much more prominent capillarizations than the sinusoids of adenomatous hyperplasia, and that the fine structures of cancerous sinusoids were also different from those of the sinusoids in fetal livers. PMID- 1310381 TI - Growth rate analysis of lung metastases appearing 18 years after resection of cutaneous adenoid cystic carcinoma. Case report and review of the literature. AB - Growth rate analysis of lung metastases of a cutaneous adenoid cystic carcinoma, which appeared 18 years after the resection of the primary tumor from the scalp is presented. The doubling times of the metastases were long compared with that of other lung metastases. They were 22 months for the metastasis in the right lung and 70 months for the metastasis in the left lung, with a shortening of the doubling time in the left side to 10.4 months in the last 4 months of observation. Backward extrapolation showed that the metastases to the lung were disseminated before the diagnosis and surgical resection of the primary tumor. To our knowledge, this is the third reported case of lung metastases from a cutaneous adenoid cystic carcinoma out of 25 documented cases. We present a review of the literature and discuss the clinical implications of our findings. PMID- 1310382 TI - Heart allograft involvement with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder. AB - We describe a 60-year-old man who underwent heart transplant and died 5 months later. At autopsy, the patient was found to have posttransplant lymphoproliferative disorder (PTLD), which was not suspected ante mortem. The PTLD involved the lung, lymph nodes, spleen, and kidney and the intima of right coronary artery of the transplanted heart. Epstein-Barr virus infection was demonstrated on direct gel and dot blot after polymerase chain reaction amplification. In situ hybridization for Epstein-Barr virus DNA confirmed the presence of Epstein-Barr virus-infected lymphocytes in the intima of the right coronary artery of the cardiac allograft. To our knowledge, this case represents the first report of involvement of a heart allograft by PTLD in which Epstein Barr virus infection of the atypical cells is documented. Although primary allograft involvement by PTLD has rarely been reported in heart transplant recipients, recognition that this may occur is important, since the lymphoid infiltrate of PTLD must be distinguished from the lymphoid infiltrate of acute rejection to avoid inappropriate therapy. PMID- 1310383 TI - Signet-ring cell carcinoma of the prostate. AB - We report an intriguing case of signet-ring cell carcinoma of the prostate, ie, a rare histopathologic pattern of prostatic carcinoma. We present the results of histologic, immunohistologic, and electron microscopic examinations in our case, and we compare the findings with those of cases that have been previously reported. Although the histopathologic findings in the rare cases of signet-ring cell carcinoma of the prostate thus far reported have varied greatly, the following conclusions can be made: (1) signet-ring cell carcinoma of the prostate is a high-grade carcinoma; (2) a prostatic primary should be considered in cases of metastatic signet-ring cell carcinoma, especially when results of gastrointestinal studies are unelucidating; and (3) staining for mucin, lipid, prostate-specific antigen, prostate-specific acid phosphatase, and carcinoembryonic antigen is variable. PMID- 1310384 TI - Cytomegalovirus colitis presenting as hematochezia and requiring resection. AB - Cytomegalovirus infection is one of the most prevalent viral infections affecting recipients of cardiac allografts. Of the various severe systemic manifestations, those in the gastrointestinal tract have a unique way of presenting, specifically in the colon where a process related to cytomegalovirus infection that involves all layers, with dilatation as a prominent clinical feature, has been suggested. We report herein a case of patient with a heart allograft who had severe episodes of rejection that responded to boosting doses of steroids. Because of persistent fever, diarrhea, hematochezia, and computed tomographic findings of the abdomen that showed a highly abnormal appearance of the ascending and transverse segments of the colon, this patient subsequently underwent celiotomy. The involved segment of the colon was found to have severe inflammation with mucosal necrosis; a subtotal colectomy was done. The abundant cytomegalovirus inclusions found in the vascular endothelium of the removed damaged segment of the colon suggest that cytomegalovirus may have been a causal factor in this form of colitis. The patient recovered uneventfully. PMID- 1310385 TI - A randomized prospective trial of acyclovir and immune globulin prophylaxis in liver transplant recipients receiving OKT3 therapy. AB - The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n = 50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing non-cytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis. PMID- 1310386 TI - Chemical cleavage of plasmid DNA by Cu(II), Ni(II) and Co(III) desferal complexes. AB - It is demonstrated that the Cu(II), Co(III) and Ni(II) complexes of a siderophore chelating drug desferal cleave DNA, in contrast to the corresponding Fe(II) complex which does not bring about DNA scission. Hydroxy radical scavengers inhibit the cleavage reaction. PMID- 1310387 TI - Evidence for heat-stable liver cytosol substance(s) capable of causing oxidative activation of fructose 1,6-bisphosphatase. AB - The endogenous fructose 1,6-bisphosphatase (FBPase) in chicken liver extract undergoes a drastic increase in activity if the pH of the extract is in the alkaline range. Greater and more consistent activation occurs when purified FBPase, placed inside dialysis sack, is incubated in liver extract. Maximal activation (over 16-fold) is accompanied by the disappearance of 4 highly reactive sulfhydryl groups (SH) per molecule of enzyme. The activating effect of the extract remains essentially unchanged after heating to 100 degrees C. Activation can be reversed by dithiothreitol. These data show the existence in liver cytosol of heat-stable substance(s) capable of activating FBPase presumably by forming disulfide bonds with the enzyme's highly reactive SH groups. PMID- 1310388 TI - Inhibition of ligand binding and antiproliferative effects of tumor necrosis factor and lymphotoxin by soluble forms of recombinant P60 and P80 receptors. AB - Tumor necrosis factor (TNF) is one of the mediators of inflammatory responses. Recently, the cDNA for two distinct receptors of TNF with predicted molecular masses of 60 kDa and 80 kDa, respectively, were isolated. In this report, we compare the inhibitory effects of these two forms of recombinant soluble TNF receptors (extracellular domains) on the ligand binding and on the antiproliferative effects of TNF and lymphotoxin (LT) in a human histiocytic lymphoma cell line (U-937). Our results show that the soluble form of the p60 receptor is approximately 100-fold more potent than the soluble form of the p80 receptor in inhibiting both the antiproliferative effects of TNF as well as in blocking TNF binding to U-937 cells. In contrast, the antiproliferative effects of LT and its binding to cells is inhibited equally by both the p60 and p80 forms of the soluble receptor. Thus, overall our results indicate that the two soluble receptors differ in their ability to inhibit TNF and LT. The impotance of these soluble receptors in blocking the harmful effects of TNF and LT is discussed. PMID- 1310389 TI - Assembly of a hybrid from the alpha subunit of Na+/K(+)-ATPase and the beta subunit of H+/K(+)-ATPase. AB - Messenger RNA for the alpha subunit of Torpedo californica Na+/K(+)-ATPase was injected into Xenopus oocytes together with that of the beta subunit of rabbit H+/K(+)-ATPase. The Na+/K(+)-ATPase alpha subunit was assembled in the microsomal membranes with the H+/K(+)-ATPase beta subunit, and became resistant to trypsin. These results suggest that the H+/K(+)-ATPase beta subunit facilitates the stable assembly of the Na+/K(+)-ATPase alpha subunit in microsomes. PMID- 1310390 TI - Two high molecular mass proteases from sea urchin sperm. AB - Two-types of high molecular mass proteases have been purified from sea urchin sperm using DEAE-Sephacel, hydroxylapatite and Superdex 200 column chromatography. Both proteases showed similar hydrolyzing activities toward synthetic peptides, but they differed in the molecular mass and peptide composition. One was probably identical to a proteasome (multicatalytic proteinase), judging from its molecular mass (650 kDa) and polypeptide composition. The other one was composed of several polypeptides with molecular masses ranging from 24 kDa to 125 kDa and its molecular mass was estimated as 950 kDa by gel filtration. These two proteases, however, were closely related to each other. Immunological studies revealed that the 950-kDa protease comprised at least five subunits of the 650-kDa protease. PMID- 1310391 TI - Monoclonal antibody to GABA binding protein, a possible GABAB receptor. AB - A monoclonal antibody has been raised against a partially purified preparation for the GABAB receptor. The antibody recognized a protein of about 80 kDa in bovine brain synaptic membrane. Immunoabsorbent agarose beads conjugated with the antibody were able to remove, without visible changes in electrophoresed profiles of total proteins, over 90% of the baclofen suppressive GABA binding activity (designated herein, GABAB receptor binding activity) in the solubilized synaptic membrane fraction. Moreover, the addition of GB-1 antibody directly inhibited the GABA binding activity in the crude synaptic membrane fraction. These results indicate that the monoclonal antibody obtained here recognizes the GABA binding protein, or more specifically a GABAB receptor. PMID- 1310392 TI - Increased expression of the 67kDa-laminin receptor gene in human small cell lung cancer. AB - Gene expression of the precursor of the 67kDa-laminin receptor was examined by Northern analysis using 11 established human lung cancer cell lines and 25 lung cancer tissues obtained by operation. As a result, one transcript, the size of which was 1.2 kb was shown in all cell lines and tissues examined. An increased level of mRNA was demonstrated in cell lines which proliferated rapidly and in small cell lung cancer cell lines. It was also indicated that gene expression of the laminin receptor was up-regulated especially in small cell lung cancer tissue. In this context, 67kDa-laminin receptor appears to be a marker for biological aggressiveness of human lung cancer. PMID- 1310393 TI - Effect of high K+ exposure on phosphoinositide metabolism in frog skeletal muscle. AB - Using [3H]myo-inositol labeled frog skeletal muscles, we have studied the effect of high K+ exposure on phosphoinositide metabolism. After 12 hours labeling, 80mM K+ exposure induced a time-dependent change. The labeling associated with phosphatidylinositol (PI) and phosphatidylinositol 4-phosphate (PIP) gradually increased and decreased, respectively. The labeled phosphatidylinositol 4,5 bisphosphate (PIP2) first decreased, and then recovered. An accumulation of the labeling in inositol phosphates was shown. In shortening the labeling to 30 min, 15 min high K+ exposure was found to only increase the labeling in all fractions. Taken together, these results show that high K+ exposure can activate the turnover of phosphoinositides, which is consistent with the hypothesis that the metabolism of phosphoinositides may regulate excitation- contraction (e-c) coupling. PMID- 1310394 TI - Investigation of sulfur containing amino acids at the lipoxygenase active site using a platinum complex. AB - Inactivation of native soybean lipoxygenase-1 was observed upon preincubation with (NEt4)[PtCl3(P(Bun)3)]. Removal of the platinum complex(es) from the inactivated enzyme by treatment with sodium diethyldithiocarbamate (Naddtc) which reverses methionine but not cysteine binding, restores most of the activity. Linoleic acid, an enzyme substrate, protects it from inactivation. The quenching of the fluorescence of the putative active site tryptophans which accompanies inactivation disappears after Naddtc reactivation. The (NEt4)[PtCl3(P(Bun)3)] inactivated enzyme iron(II) cannot be oxidized at variance with that of the native or Naddtc reactivated enzyme, as checked by EPR spectroscopy. These results show that at least one methionine is close to the iron binding site in soybean lipoxygenase-1. PMID- 1310395 TI - Histamine and calcium are independently regulated intracellular mediators of lymphocyte mitogenesis. AB - In addition to cytosolic calcium ([Ca2+]i), intracellular histamine has been implicated as a mediator of mitogenesis in normal mouse spleen cells stimulated by the plant lectin, concanavalin (Con) A. We have linked the growth-promoting action of this amine with its binding to distinct intracellular sites, designated HIC, in microsomes and nuclei and shown that the proliferative response of lymphocytes can be blocked by antagonizing the binding of histamine to HIC by N,N diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), or by depleting intracellular histamine levels by the specific irreversible inhibitor of histidine decarboxylase, alpha-FMH. We now demonstrate that, at a concentration which completely inhibits both 3H-histamine binding to HIC and 3H-thymidine incorporation into DNA, DPPE fails to block the acute (30 seconds) rise in [Ca2+]i in spleen cells exposed to Con A. Conversely, the calcium channel antagonist, verapamil, suppresses the Con A-induced rise in [Ca2+]i at a concentration which correlates with its inhibition of thymidine incorporation into DNA, but does not prevent histamine synthesis or bind to HIC. Thus, in Con A stimulated lymphocytes, intracellular histamine and calcium appear to be independently regulated, but essential, mediators of the proliferative response. PMID- 1310397 TI - Effects of HS-142-1, a novel non-peptide ANP antagonist, on diuresis and natriuresis induced by acute volume expansion in anesthetized rats. AB - In this study we used HS-142-1, a novel non-peptide antagonist for the atrial natriuretic peptide (ANP) receptor, to clarify the possible physiological significance of ANP in acute hypervolemia. Substantial volume expansion in anesthetized rats induced a strong diuresis and natriuresis. These renal responses were significantly blocked by HS-142-1 at a dose of 3.0 mgkg-1 i.v. This observation suggests that ANP and its guanylyl cyclase-coupled receptor are, under the present conditions, physiologically involved that appears to be responsible for the renal responses in the volume homeostasis. PMID- 1310396 TI - Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q. AB - The amino acid sequence of the sodium channel alpha subunit from adult human skeletal muscle has been deduced by cross-species PCR-mediated cloning and sequencing of the cDNA. The protein consists of 1836 amino acid residues. The amino acid sequence shows 93% identity to the alpha subunit from rat adult skeletal muscle and 70% identity to the alpha subunit from other mammalian tissues. A 500 kb YAC clone containing the complete coding sequence and two overlapping lambda clones covering 68% of the cDNA were used to estimate the gene size at 35 kb. The YAC clone proved crucial for gene structure studies as the high conservation between ion channel genes made hybridization studies with total genomic DNA difficult. Our results provide valuable information for the study of periodic paralysis and paramyotonia congenita, two inherited neurological disorders which are caused by point mutations within this gene. PMID- 1310398 TI - Lysosome inhibitors enhance the ability of cyclic AMP-elevating agents to induce the LDL receptor in human vascular smooth muscle cells. AB - In human vascular smooth muscle cells cyclic AMP elevation by forskolin increases synthesis of the LDL receptor by a mechanism which appears independent of sterol control. This increased receptor synthesis is further enhanced by chloroquine. Both forskolin and prostaglandin E1 increase the number of cell surface LDL receptors indicating that prostaglandins could exert physiological control over LDL metabolism. This effect is enhanced synergistically by chloroquine. The stimulation by forskolin of LDL receptor synthesis and expression leads to increased metabolism of apo-B and increased hydrolysis of LDL-borne cholesteryl ester. These effects of cyclic AMP on the activity of the LDL pathway are enhanced more than additively by preincubation with the reversible lysosomal inhibitor NH4Cl. Thus cyclic AMP causes up-regulation of the LDL receptor pathway resulting in increased rates of LDL metabolism but this effect can be damped or masked in cell culture by a cyclic AMP-sensitive lysosomal event, probably the acute stimulation of lysosomal cholesterol ester hydrolase. PMID- 1310400 TI - Effect of D2O on maize plasmalemma ATPase and electron transport coupled proton pumping. AB - Heavy water (D2O) has been used as a putative inhibitor of the plasma membrane H(+)-ATPase and the plasma membrane redox system. Concentrations above 50% D2O inhibited H+ secretion and the plasma membrane redox system of Zea mays L. roots. Inhibition of H+ secretion by vanadate was reduced in presence of D2O. The plasma membrane of roots was transiently depolarized after the addition of heavy water in concentrations above 5%. The repolarization of the plasma membrane that takes place while the H+ secretion is still reduced by heavy water indicates that, despite the overall inhibiting effect of D2O, the plant is still able to regulate the membrane potential. PMID- 1310399 TI - Extracellular ATP stimulates increases in Na+/K+ pump activity, intracellular pH and uridine uptake in cultures of mammalian cells. AB - Using 3T3 and 3T6 mouse fibroblasts and A431 epidermoid carcinoma cells, we previously observed that extracellular ATP and ADP were mitogens and they synergized with other growth factors (Huang, N., Wang, D. and Heppel, L. A. (1989) Proc. Natl. Acad. Sci. USA 86, 7904-7908). We now report that ATP and ADP stimulated Na+ entry, intracellular alkalinization and Na+/K+ pump activity, which are early events that had been proposed to play a central role in DNA synthesis. In addition, ATP, ADP and AMPPNP stimulated uridine uptake by a pathway involving arachidonic acid metabolism. In A431 cells, activation of protein kinase C also contributed to ATP-dependent stimulation of uridine uptake. Concentrations of indomethacin and pertussis toxin which inhibited uridine uptake also blocked arachidonic acid metabolism and DNA synthesis. ATP acted as a competence factor. Interestingly, ATP did not have to be continuously present to stimulate uridine uptake. It was equally effective even when it was washed away after brief treatment of cells. PMID- 1310401 TI - Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors. AB - The energy metabolism of an atypical multidrug resistant human small cell lung carcinoma cell line (GLC4/ADR) was studied. The glycolytic rate was 30% reduced and the glucose-6-phosphate dehydrogenase activity 2-fold increased in GLC4/ADR compared to the parental sensitive line (GLC4). Although mitochondrial respiration activities were similar in both cell lines, GLC4/ADR was more sensitive to the antimitochondrial drugs doxycycline and oligomycin, while cross resistance was observed for the glycolytic inhibitor 2-deoxyglucose and for the antimitochondrial drug rhodamine-123. Continuous incubation with doxycycline induced a dramatic reduction of mitochondrial mRNAs in both cell lines, whereas a strong reduction of the nuclear-coded mRNA for subunit IV of cytochrome c oxidase was induced in GLC4/ADR only. Incubation with doxycycline had an additive effect on the cytotoxicity of adriamycin in both cell lines. Thus, a form of collateral sensitivity to antimitochondrial drugs may exist in atypical multidrug resistant cell lines. PMID- 1310402 TI - Regulation of intracellular Mg2+ by superoxide in amnion cells. AB - Changes of intracellular free Mg2+ concentration ([Mg2+]i) in human amnion cells induced by superoxide anion were determined using a highly Mg(2+)-sensitive fluorescent dye Mg(2+)-fura2 or Mg(2+)-indol. Superoxide anion, produced by addition of xanthine oxidase to hypoxanthine, induced decrease of [Mg2+]i. The decrease was significantly inhibited by an anion channel blocker, 4,4'diisothiocyano-2,2' disulfonic acid stilbene (DIDS). Superoxide dismutase (SOD), injected into cells by cell fusion, also inhibited the change of [Mg2+]i, but catalase did not. Superoxide anion induced prompt increase of intracellular pH (pHi) as well as decrease of [Mg2+]i and subsequently activated the increase of intracellular free Ca2+ ([Ca2+]i) and the release of arachidonate. In contrast to superoxide anion, NH4Cl which induces increase of pHi in amnion cells increased [Mg2+]i. The elevation of basal level of [Mg2+]i by Mg(2+)-ionophore inhibited the change of [Ca2+]i and the release of arachidonate induced by superoxide anion. These results suggest that superoxide anion, transported through anion channels into cells, decreases [Mg2+]i directly, not due to a pH effect and that the decrease of [Mg2+]i may regulate biological functions of the cells via increase of [Ca2+]i. PMID- 1310403 TI - Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor. AB - To understand the role of mitochondria in carcinogenesis, we compared the amount of deleted mtDNAs between human hepatic tumors and surrounding cirrhotic portion of the liver of ten patients by using polymerase chain reaction (PCR). Multiple mtDNA deletions were detected in cirrhotic portion, but no deletions were detected in the tumor portion. Direct sequencing of the fragments revealed a 7,079-bp deletion (nucleotide position 8,992-16,072) involving no direct repeated sequences and a 7,436-bp deletion (position 8,649-16,084) involving a 12-bp directly repeated sequence of 5'-CATCAACAACCG-3' exists in both the ATP6 gene and the D-loop region. These mtDNA mutations could be one of the endogenous factors that induce somatic mutations in nuclear genome and etiologically contribute to human carcinogenesis. PMID- 1310404 TI - Biochemical characterization of binding sites for dihydropyridine and omega conotoxin in brain of adult chicken. AB - Binding studies using the calcium channel blockers omega-conotoxin and dihydropyridine revealed a rather equal amount of binding sites in brain from adult chicken. The omega-conotoxin binding sites could be solubilized using digitonin, without substantial loss, whereas a great decrease in dihydropyridine binding sites was observed, indicating that both types of binding sites have different sensitivity to solubilization. In contrast to ion exchange chromatography where both binding sites comigrated, glycoprotein affinity chromatography led to a different partition of the binding sites in the flow through and eluate fractions. Our results indicate that both types of calcium channel blockers bind to different targets in adult chicken. PMID- 1310405 TI - Inhibitory action of the potassium channel opener BRL 38227 on agonist-stimulated phosphoinositide metabolism in bovine tracheal smooth muscle. PMID- 1310407 TI - Calcium channels and their involvement in cardiovascular disease. AB - The widespread distribution of L-type Ca2+ channels in the cardiovascular system makes that system a natural 'target' for drugs which inhibit L-type Ca2+ channel activity. Now that tissue-dependent differences in the chemical composition of the calcium antagonist binding sites have been recognized it may be possible to develop drugs with enhanced tissue selectivity. The search for new compounds should not be restricted to improvements in tissue selectivity, however. Some of the ancillary properties of the L-type Ca2+ channel inhibitors--including their ability to protect against lipid peroxidation--should not be lost because these ancillary properties may contribute significantly to their usefulness as therapeutic agents. PMID- 1310406 TI - The internal calcium store in airway muscle: emptying, refilling and chloride. Possible new directions for drug development. AB - This review examines the ionic mechanisms underlying acetylcholine (Ach) depolarization of airway smooth muscle and suggests that multiple mechanisms are involved. Increased chloride and nonspecific cation conductance, and decreased or rapidly inactivating potassium conductances seem to be involved. Chloride ions also seem to play an important role in determining whether Ca2+ remains inside or is replenished in the sarcoplasmic reticulum (SR). The physiological role of Ach induced depolarization is analysed and is suggested to be the promotion of the refilling of Ca2+ stores, partly through a direct refilling of SR-Ca2+ stores by way of an L-type Ca2+ channel. This refilling is promoted by Ca2+ channel agonists and is independent of the transmembrane potential. Ca(2+)-release by a variety of agonists leads to depolarization and stable membrane oscillations which depend on the action of the Ca(2+)-store uptake mechanisms in order to function. These oscillations may play a role in prolonged bronchoconstriction. Better knowledge of the control mechanisms of Cai2+ is likely to reveal new targets for the therapy of asthma and provide a better understanding of the function of airway smooth muscle. PMID- 1310408 TI - Importance of kinetic parameters for the tissue selectivity of calcium antagonists. PMID- 1310409 TI - The anticollagenolytic potential of lymecycline in the long-term treatment of reactive arthritis. AB - OBJECTIVE: We sought to determine the antiinflammatory properties of lymecycline in the long-term treatment of reactive arthritis (ReA). METHODS: Quantitative assay of collagenase activity by densitometry after sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: Therapeutic levels of lymecycline do not directly inhibit the activity of human neutrophil interstitial collagenase, but can prevent the oxidative activation of latent human neutrophil collagenase. CONCLUSION: This non-antimicrobial, anticollagenolytic property of lymecycline may contribute to its therapeutic efficacy in the treatment of patients with ReA. PMID- 1310411 TI - Rapid screening of libraries with radiolabeled DNA sequences generated by PCR using highly degenerate oligonucleotide mixtures. AB - The PCR technique can use protein-derived oligonucleotide sequences as primers to develop probes for screening recombinant libraries. Here we report a method with highly degenerate mixtures of oligonucleotides as primers for the PCR that eliminates the need to identify or isolate the DNA sequences derived by PCR. The method uses the pool of PCR-generated DNA sequences radiolabeled during the extension reaction as a probe, combined with highly stringent hybridization and wash conditions that permit only homologous sequences to hybridize and therefore target desired clones. This technique was used successfully to clone the receptor for tumor necrosis factor. PMID- 1310410 TI - Interactions between anticollagen antibodies and chondrocytes. AB - OBJECTIVE: To investigate the interactions between anticollagen antibodies and living chondrocytes. METHODS: Mouse monoclonal anti-type II collagen (anti-CII) antibodies, rabbit anti-human CII, and rat anti-CII, anti-CIV, anti-CV, anti-CVI, and anti-CIX were studied in vitro to determine their ability to bind to the plasma membrane of living bovine chondrocytes. RESULTS: Mouse monoclonal anti CII, rabbit anti-CII, and rat anti-CII, anti-CV, and anti-CIX were shown to bind in vitro to the plasma membrane of bovine chondrocytes. Antibody binding was not observed with anti-CIV, or with chondrocytes previously incubated with bacterial collagenase. A significant increase in chondrocyte caseinase and collagenase secretion was observed following sequential incubation with the monoclonal antibodies and a source of activating cytokines. CONCLUSION: These results suggest that collagen autoantibodies may exert some of their pathogenic effects on cartilage through interactions with resident chondrocytes, leading to modulation of the rate of secretion of cartilage matrix-degrading enzymes. PMID- 1310412 TI - Detection of point mutations by SSCP of PCR-amplified DNA after endonuclease digestion. PMID- 1310413 TI - A general method of quantitative PCR analysis of mRNA levels for members of gene families: application of GABAA receptor subunits. PMID- 1310414 TI - Effects of vitamin D-binding proteins on HL-60 cell differentiation induced by 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D. AB - Monocytic differentiation-inducing activity of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 [26,27-F6-1 alpha,25-(OH)2D3] was re-evaluated in human promyelocytic leukemia (HL-60) cells in serum-supplemented or serum-free culture. The order of in vitro potency for reducing nitroblue tetrazolium (NBT) was 26,27-F6-1 alpha,25-(OH)2D3 greater than 1 alpha, 25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] = 26,26,26,27,27,27-F6-1 alpha,23(S), 25-trihydroxyvitamin D3 [26,27-F6-1 alpha,23(S), 25-(OH)3D3] under serum-supplemented culture conditions, whereas the order was 1 alpha, 25-(OH)2D3 = 26,27-F6-1 alpha,25-(OH)2D3 greater than 26,27-F6-1 alpha,23(S), 25-(OH)3D3 under serum-free culture conditions. This rank order for differentiation-inducing activity under serum-free culture conditions correlated well with the binding affinity of these analogs for vitamin D3 receptor of HL-60 cells. The order of relative % binding affinity for the vitamin D-binding protein in fetal calf serum was 1 alpha,25-(OH)2D3 (100%) much greater than 26,27-F6-1 alpha,25-(OH)2D3 (5.1%) greater than 26,27-F6-1 alpha,23(S), 25-(OH)3D3 (less than 1%). These results suggest that serum vitamin D-binding proteins apparently modulate monocytic differentiation of HL-60 cells by 26,27-F6-1 alpha,25-(OH)2D3 under serum-supplemented culture conditions. PMID- 1310415 TI - Effect of ACTH on steroidogenic enzymes in guinea pig fasciculata-glomerulosa cells: changes in activity and mRNA levels. AB - Adrenocorticotropin (ACTH) is known to exert an acute effect on adrenal steroidogenesis as well as long-term effects by regulation of gene expression. In order to further study the long-term action of ACTH, guinea pig fasciculata glomerulosa (FG) cells in primary culture were treated for up to 72 h with ACTH. The effects of this treatment on steroid secretion, enzyme activity and mRNA levels for steroid enzymes were measured. While the rate of 17-deoxy C-21 steroid secretion decreased over the 72-h period of incubation with ACTH, the 17-hydroxy C-21 steroid secretion rate remained constant for the first 24 h of incubation and declined thereafter; the rate of 4-ene C-19 steroid secretion increased over the 72-h incubation period. ACTH treatment increased 17-hydroxylase and 17,20 lyase activities and the maximal stimulation was reached after 48 h. In contrast, the activity of 21-hydroxylase (P450c21) steadily declined over the 72-h incubation period. ACTH also caused an increase in mRNA levels for P450c21, 17 hydroxylase and 17,20-lyase (P450c17), 3 beta-hydroxysteroid dehydrogenase 4-ene 5-ene-isomerase (3 beta-HSD) and cholesterol side-chain cleavage enzyme (P450scc). The maximal stimulation for the four mRNAs was observed after 18 h of incubation with ACTH, decreasing afterwards except for P450c17 mRNA levels which remained elevated over the 72-h incubation period. Despite the increase in mRNA levels for 3 beta-HSD and P450c21, no increase in their respective enzyme activities was observed and 21-hydroxylase activity even declined over the 72-h incubation period with ACTH, thus suggesting that mechanism(s) other than gene expression alone regulate steroid secretion in FG cells. In conclusion ACTH caused major changes in steroid distribution due to increased 17-hydroxylase and 17,20-lyase activities and decreased 21-hydroxylase activity in FG cells in culture. Moreover, our data revealed major differences in the induction of mRNAs for steroidogenic enzymes and their activities following ACTH treatment. PMID- 1310416 TI - Effect of chronic ACTH treatment on guinea-pig adrenal steroidogenesis: steroid plasma levels, steroid adrenal levels, activity of steroidogenic enzymes and their steady-state mRNA levels. AB - We report here the effects of a 7-day treatment of guinea-pigs with ACTH on adrenal mRNA levels for steroid-transforming enzymes. Adrenal 3 beta hydroxysteroid dehydrogenase 4-ene-5-ene-isomerase (3 beta-HSD), 17-hydroxylase, 17,20-lyase, 21-hydroxylase and 11-hydroxylase activities were also examined as well as plasma and adrenal steroid levels. Our data reveal that chronic ACTH treatment stimulated all post-pregnenolone enzyme activities in glomerulosa fasciculata cells. Plasma steroid levels increased 8 h after the last injection of ACTH and returned to the control levels 24 h later whereas, in the adrenal, the content in steroids in the group sacrificed 8 h after the last injection of ACTH were similar to the values of the control group and decreased markedly 24 h later. It is suggested that the steroid turn-over in the adrenal may be affected by the chronic ACTH-treatment. On the other hand, despite the significant stimulation in steroid-transforming enzyme activities, our data reveal that chronic ACTH administration caused a decrease in mRNA levels for P450c21 and P450c17 while P450scc, 3 beta-HSD and P450c11 remained unchanged. Taken together, these results suggest that in vivo chronic ACTH-treatment of guinea-pigs increases adrenal steroidogenic capacity by increasing steroid secretion and steroid enzyme activity. Moreover, the chronic treatment with ACTH may have a post-transcriptional effect on steroidogenic enzymes gene expression by affecting the half-life of their mRNAs. PMID- 1310417 TI - Interaction of Tn501 mercuric reductase and dihydroflavin adenine dinucleotide anion with metal ions: implications for the mechanism of mercuric reductase mediated Hg(II) reduction. AB - The flavoprotein Tn501 mercuric reductase (MerA) catalyzes the reduction of Hg(II) to Hg(0) through the intermediacy of the tightly bound two-electron reduced cofactor FADH-. To gain insight into the MerA mechanism, the interaction of the holoenzyme or free FADH- with various metal ions was investigated. The free two-electron-reduced FAD cofactor, FADH-, readily reduces a variety of metal ions, provided they have suitably high redox potentials. For Hg(II) with various ligands, the rate of reduction is inversely proportional to the stability of the Hg(II)-ligand complex. These results are consistent with the free cofactor reducing metal ions by an outer-sphere electron transfer mechanism. In contrast, MerA can tightly bind several redox labile metal ions, but only Hg(II) is reduced. The inability of MerA to reduce these bound metal ions may suggest that MerA differs from free FADH- and utilizes an inner-sphere electron transfer mechanism in Hg(II) reduction. PMID- 1310418 TI - Conformational rigidity of specific pyrimidine residues in tRNA arises from posttranscriptional modifications that enhance steric interaction between the base and the 2'-hydroxyl group. AB - In order to elucidate roles of the 2'-O-methylation of pyrimidine nucleotide residues of tRNAs, conformations of 2'-O-methyluridylyl(3'----5')uridine (UmpU), 2'-O-methyluridine 3'-monophosphate (Ump), and 2'-O-methyluridine (Um) in 2H2O solution were analyzed by one- and two-dimensional proton NMR spectroscopy and compared with those of related nucleotides and nucleoside. As for UpU and UmpU, the 2'-O-methylation was found to stabilize the C3'-endo form of the 3' nucleotidyl unit (Up-/Ump-moiety). This stabilization of the C3'-endo form is primarily due to an intraresidue effect, since the conformation of the 5' nucleotidyl unit (-pU moiety) was only slightly affected by the 2'-O-methylation of the 3'-nucleotide unit. In fact even for Up and Ump, the 2'-O-methylation significantly stabilizes the C3'-endo form by 0.8 kcal/.mol-1. By contrast, for nucleosides (U and Um), the C3'-endo form is slightly stabilized by 0.1 kcal/.mol 1. Accordingly, the stabilization of the C3'-endo form by the 2'-O-methylation is primarily due to the steric repulsion among the 2-carbonyl group, the 2'-O-methyl group and the 3'-phosphate group in the C2'-endo form. For some tRNA species, 2 thiolation of pyrimidine residues is found in positions where the 2'-O methylation is found for other tRNA species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310419 TI - 1H NMR studies of a biosynthetic lacto-ganglio hybrid glycosphingolipid: confirmation of structure, interpretation of "anomalous" chemical shifts, and evidence for interresidue amide-amide hydrogen bonding. AB - Glycosphingolipids bearing GlcNAc beta 1----3 and GalNAc beta 1----4 linked to beta-Gal of lactosylceramide (lacto-ganglio hybrids), first isolated from a murine myelogenous leukemia cell line [Kannagi, R., Levery, S. B., & Hakomori, S. (1984) J. Biol. Chem. 259, 8444-8451], have since been found as normal components of mullet roe and English sole liver. In order to clarify the biosynthetic pathways responsible for its occurrence both as a product of normal tissues and as a possible mammalian cancer-associated antigen, the lacto-ganglio hybrid core structure LcGg4Cer was synthesized from Lc3Cer using a GalNAc beta 1----4 transferase preparation from English sole liver. A preliminary characterization of the enzyme, which may be identical to the GalNAc T-1 responsible for synthesis of GM2 ganglioside, is presented. The enzymatically synthesized product was analyzed by 1- and 2-D 1H NMR spectroscopy, confirmining its primary structure as GalNAc beta 1----4-(GlcNAc beta 1----3)Gal beta 1----4Glc beta 1----1Cer. In addition to assigning all nonexchangeable glycosyl proton resonances, measurements of several properties of the amide NH protons, including chemical shift, coupling constants, exchange rates, and temperature shift coefficients, were obtained and compared to those in the simpler constituent triglycosylceramides, Lc3- and Gg3Cer. An approximate three-dimensional structure for LcGg4Cer is proposed, consistent with all data obtained, which should be useful in discussing the results of 1H NMR analysis of compounds containing this core tetrasaccharide. The structure is characterized by an unusual arrangement of terminal N-acetylhexosamine residues, resulting in a pi-H hydrogen-bonding interaction between their acetamido groups. PMID- 1310420 TI - Characterization of a recombinant extracellular domain of the type 1 tumor necrosis factor receptor: evidence for tumor necrosis factor-alpha induced receptor aggregation. AB - An expression plasmid encoding the extracellular portion of the human tumor necrosis factor (TNF) type 1 receptor (TNF-R1) was constructed and used to generate a stable cell line secreting soluble TNF-R1 (sTNF-R1). The sTNF-R1 was purified, and its biochemical properties and its interactions with human TNF alpha were examined. SDS-PAGE resolved the purified sTNF-R1 into three bands of approximate Mr 24,200, 28,200, and 32,800. Sedimentation equilibrium analysis gave a molecular weight of 25,000 for sTNF-R1 whereas the molecular weight obtained by gel filtration chromatography was approximately 55,000-60,000. Scatchard analysis of [125I]TNF-alpha binding to sTNF-R1 revealed high-affinity binding (Kd = 93 pM), comparable to that observed for the intact receptor on whole cells. Competitive binding experiments showed that sTNF-R1 has a 50-60-fold higher affinity for TNF-alpha than for TNF-beta, in contrast to the equal affinities of TNF-alpha and TNF-beta for the full-length TNF-R1 transiently expressed in mammalian cells. The sTNF-R1 was found to block the cytotoxicity of TNF-alpha and TNF-beta on a murine L-M cell assay. The sizes of the sTNF-R1.TNF alpha complex determined by gel filtration chromatography and sedimentation equilibrium were approximately 141 and 115 kDa, respectively. The stoichiometry of the complex was examined by Scatchard analysis, size-exclusion chromatography, HPLC separation, amino acid composition, sequence analysis, and sedimentation equilibrium. The data from these studies suggest that at least two molecules of sTNF-R1 can bind to a single TNF-alpha trimer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310421 TI - Linkage between proton binding and amidase activity in human gamma-thrombin. AB - The amidase activity of human gamma-thrombin has been studied in the pH range 6 10 as a function of NaCl concentration and temperature. As recently found for human alpha-thrombin [Di Cera, E., De Cristofaro, R., Albright, D.J., & Fenton, J.W., II (1991) Biochemistry 30, 7913-7924], the Michaelis-Menten constant, Km, shows a bell-shaped dependence over this pH range with a minimum around pH 7.9 in the presence of 0.1 M NaCl at 25 degrees C. The catalytic constant, kcat, has a bell-shaped pH dependence with a maximum around pH 8.6. A thermodynamic analysis of these parameters has enabled a characterization of the linkage between proton and substrate binding, its dependence on NaCl concentration, and the relevant entropic and enthalpic contributions to binding and catalytic events. Three groups seem to be responsible for the control of gamma-thrombin amidase activity as a function of pH. One of these groups has pK values that are significantly different from those found for alpha-thrombin, and all groups show slightly perturbed enthalpies of ionization. The dependence of gamma-thrombin amidase activity on NaCl concentration is different from that of alpha-thrombin. Increasing NaCl concentration always decreases the substrate affinity for the enzyme in the case of alpha-thrombin, regardless of pH. In the case of gamma thrombin, such an effect is observed only in the pH range 7.5-9, and a reversed linkage is observed at pH less than 7 and greater than 9.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310422 TI - Artificial pigments of halorhodopsin and their chloride pumping activities. AB - Halorhodopsin (HR), the light-driven chloride pump of Halobacterium halobium, was bleached with hydroxylamine and regenerated with all-trans-retinal under several different conditions. The largest recovery of the pigment was found with apoprotein obtained from detergent-free HR [HR(BB)]. To compare the chloride pumping mechanism of HR with that of bacteriorhodopsin (BR; the light-driven proton pump of the same bacteria), HR pigment analogues were reconstituted with the bleached HR (BB) and retinal analogues. The corresponding BR pigment analogues have previously been shown to have little or no proton-pumping activity, except for retinal2 (3,4-dehydroretinal). Pigment analogues with 13 demethylretinal or retinal2 showed an "opsin shift" similar to that of the all trans-retinal pigment of both HR and BR. Opsin shifts of the pigments of 9-12 phenylretinal and 3,7-dimethyl-2,4,6,8-decatetraenal and haloopsin are slightly different from those of the corresponding BR pigment analogues, presumably reflecting differences of the chromophoric structures in HR and BR. In addition to the spectral properties, the effect of chloride ion on deprotonation of the Schiff base was measured. These pigment analogues showed the "chloride effect" (a shift of the pK value for deprotonation of the Schiff base), but a smaller one than that seen in HR. For a measurement of the chloride-pumping activity, each retinal analogue was added to a culture of L07 cells (BOP-, HOP+, Ret-), and the activity was measured with the cell suspension. Only cultures with retinal or retinal2 showed chloride-pumping activity, as is true for proton pumping by BR. This suggests that a similar retinal-protein interaction is necessary for both ion pumps. PMID- 1310423 TI - Simultaneous internalization and binding of calcium during the initial phase of calcium uptake by the sarcoplasmic reticulum Ca pump. AB - The kinetics of Ca2+ transport mediated by the sarcoplasmic reticulum (SR) Ca ATPase were investigated by rapid kinetic techniques that either measure the disappearance of Ca2+ from the medium [stopped-flow photometry of Ca2+ indicators or rapid filtration (method 1)] or directly detect the changes in the accessibility of Ca2+ to the exterior of the membrane, i.e., occlusion of Ca2+ within the Ca pump and Ca2+ transport into the lumen of SR vesicles [EGTA quench (method 2)]. SR vesicles were preincubated in micromolar Ca2+ to form the E.2Cacyt intermediate of the Ca-ATPase, and then Ca2+ transport was initiated by addition of ATP. It was found that Ca2+ uptake measured by method 1 began with no lag phase, in spite of the prediction of kinetic models of the Ca-ATPase. Instead, the time course of Ca2+ uptake was found to have two components: a fast and a slow phase, similar to that obtained using method 2, although the rate constant of the fast phase determined by method 1 was considerably lower than that measured by method 2. The fast phase of Ca2+ uptake measured by method 1 was not influenced by either Ca2+ ionophore or detergent treatment, whereas the slow phase was diminished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310425 TI - An organic radical in the lysine 2,3-aminomutase reaction. AB - Lysine 2,3-aminomutase from Clostridium SB4 has been studied by electron paramagnetic resonance (EPR) spectroscopy at 77 K. Although the reaction catalyzed by this enzyme is similar to rearrangements catalyzed by enzymes requiring adenosylcobalamin, lysine 2,3-aminomutase does not utilize this cofactor. The enzyme instead contains iron-sulfur clusters, cobalt, and pyridoxal phosphate and is activated by S-adenosylmethionine. Subsequent to a reductive incubation procedure that is required to activate the enzyme, EPR studies reveal the appearance of an organic radical signal (g = 2.001) upon addition of both L lysine and S-adenosylmethionine. The radical signal is complex, having multiple hyperfine transitions. The total radical concentration is proportional to enzyme activity and decreases in parallel with the approach to chemical equilibrium between alpha-lysine and beta-lysine. The signal changes over the time course of the reaction in a way that suggests the presence of more than one radical species, with different relative proportions of species in the steady state and equilibrium state. Isotopic substitution experiments show that unpaired spin density resides on the molecular framework of lysine and that solvent exchangeable protons do not participate in strong hyperfine coupling to the radical. The results indicate that lysine radicals participate in the rearrangement mechanism. PMID- 1310424 TI - Inhibition of tyrosine Z photooxidation after formation of the S3 state in Ca(2+) depleted and Cl(-)-depleted photosystem II. AB - Ca2+ and Cl- are obligatory cofactors in photosystem II (PS-II), the oxygen evolving enzyme of plants. The sites of inhibition in both Ca(2+)- and Cl(-) depleted PS-II were compared using EPR and flash absorption spectroscopies to follow the extent of the photooxidation of the redox-active tyrosine (TyrZ) and of the primary electron donor chlorophyll (P680) and their subsequent reduction in the dark. The inhibition occurred after formation of the S3 state in Ca(2+) depleted PS-II. In Cl(-)-depleted photosystem II, the inhibition occurred after formation of the S3 state in about half of the centers and probably after S2TyrZ+ formation in the remaining centers. After the S3 state was formed in Ca(2+)- and Cl(-)-depleted photosystem II, electron transfer from TyrZ to P680 was inhibited. This inhibition is discussed in terms of electrostatic constraints resulting from S3 formation in the absence of Ca2+ and Cl-. PMID- 1310426 TI - Triple-helix formation is compatible with an adjacent DNA-protein complex. AB - The effect of oligonucleotide-directed triple-helix formation on the binding of a protein to an immediately adjacent sequence has been examined. A double-stranded oligonucleotide was designed with a target site for the binding of a pyrimidine oligonucleotide located immediately adjacent to the recognition sequence for the herpes simplex virus type 1 (HSV-1) origin of replication binding protein, which is encoded by the UL9 gene of HSV-1. Since the optimal conditions for the binding of the UL9 protein and the pyrimidine oligonucleotide to the duplex DNA are markedly different, a pyrimidine oligonucleotide was designed to optimize binding affinity and specificity for the target duplex oligonucleotide. Consideration was given to length and sequence composition in an effort to maximize triple-strand formation under conditions amenable to the formation of the UL9-DNA complex. Using gel mobility shift assays, a trimolecular complex composed of duplex DNA bound to both a third oligonucleotide strand and the UL9 protein was detected, indicating that the UL9-DNA complex is compatible with the presence of a triple helix in the immediately adjacent sequences. PMID- 1310427 TI - Could an outbreak of poliomyelitis occur in the UK? PMID- 1310428 TI - Polyomavirus-mediated transformation: a model of multistep carcinogenesis. PMID- 1310429 TI - Intrauterine diagnosis of cytomegalovirus and rubella infections by amniocentesis. PMID- 1310430 TI - Diet and calcium stones. AB - OBJECTIVE: To review the current literature on the dietary modification of urinary risk factors as a means of reducing the likelihood of recurrent stone formation and to develop practical dietary recommendations that might be useful to this end. DATA SOURCES: MEDLINE was searched for English-language articles published from 1983 to 1990. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA SYNTHESIS: Information on the dietary intake of calcium, oxalate, protein, sodium and fibre and on alcohol and fluid intake was used to develop practical guidelines on dietary modification. CONCLUSION: Dietary modification plays an important role in the reduction of urinary risk factors in patients with calcium stone disease of the urinary tract. As an initial form of prevention attention should be directed toward moderating the intake of calcium, oxalate, protein, sodium and alcohol and increasing the intake of fibre and water. Future research should include an assessment of the long-term reduction of dietary and urinary risk factors and the rates of recurrence of calcium stones. PMID- 1310431 TI - Does malignant small round cell tumor of the thoracopulmonary region (Askin tumor) constitute a clinicopathologic entity? An analysis of 30 cases with immunohistochemical and electron-microscopic support treated at the Institute Gustave Roussy. AB - The morphology and clinical outcome of 30 patients with malignant small round cell tumors located in the thoracopulmonary region (Askin tumor) are reported. Histologically, all tumors had similar patterns, with small round-to-oval cells and a lobulated stroma. Immunohistochemical analysis always resulted in positive staining for one or several neural markers. No significant differences were found compared with the immunomarkers in 26 typical Ewing's sarcomas located outside the thoracic wall. In three specimens, electron microscopy confirmed the presence of membrane-bound neurosecretory granules. It was confirmed that there is a remarkable similarity among all malignant small round cell tumors, including Askin tumor and Ewing's sarcoma. Overall survival was poor with a 2-year rate of 38% and a 6-year rate of 14%. PMID- 1310432 TI - A clinicopathologic study of mucinous gastric carcinoma. AB - A clinicopathologic study of 42 mucinous gastric carcinomas (MGC) and 73 nonmucinous gastric carcinomas (NGC) was done. The tumor was defined as MGC when more than one half of tumor area had mucin pools. The 5-year survival rate for curatively treated patients was almost the same in MGC (58%) and NGC (56%), and clinicopathologic features, except for lymphatic permeation, showed no significant difference between MGC and NGC. Findings in MGC patients who died of a recurrence within 3 years included total gastrectomy, upper location, large size, infiltrative growth, extraserosal invasion, positive lymph node metastasis, more advanced stage, and a noncurative operation. There was no significant correlation between the degree of mucin content and other data, including the prognosis. Histologically, MGC were divided into well-differentiated and poorly differentiated types, according to the degree of glandular formation of the tumor cells. In patients with well-differentiated MGC, the age of onset was older, tumor growth was localized, and there were metastases to the liver. In patients with poorly differentiated MGC, the age of onset was younger, tumor growth was infiltrative, and there was peritoneal dissemination. These results show that the biologic behavior of MGC is similar to that of NGC and that the lesion basically is determined by the histologic subtype, not by the mucin content. PMID- 1310433 TI - Diffusely infiltrating primary colorectal carcinoma of linitis plastica and lymphangiosis types. AB - A review of 2369 cases of resected primary colorectal carcinoma identified 15 cases of diffusely infiltrating colorectal carcinoma. Depending on the histologic pattern and extent, these cases were classified as linitis plastica (LP) type (seven cases) or lymphangiosis (LA) type (eight cases). The LP type consisted of poorly differentiated adenocarcinoma or signet ring cell carcinoma; it showed an annularly thickened and rigid bowel wall. The LA type consisted of moderately differentiated adenocarcinoma. The colon wall of the LA type was hemilaterally thickened at the mesenteric side. The prognosis was extremely poor for both types. The LP type mainly had peritoneal dissemination (70%), but the LA type frequently had distant metastasis (88%). Early diagnosis and curative operation are important for both types; however, the LA type also requires therapy for distant metastasis. PMID- 1310434 TI - Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy. AB - To establish useful predictors of the intrahepatic recurrence of hepatocellular carcinoma (HCC) after partial hepatectomy, retrospective analyses of clinical and pathologic factors were done in 112 of 206 patients treated by partial hepatectomy. The absence or presence of intrahepatic recurrence was confirmed by a follow-up study. Cancer-free survival rates after 1, 2, 3, and 5 years were 54.8%, 36.7%, 32.5%, and 25.6%, respectively. The significant factors affecting recurrence were tumor size, number of tumors, cancer cell infiltration of the fibrous capsule of the tumor, portal involvement, and stage of the tumor, but the grade of anaplasia according to Edmondson-Steiner's classification and the severity of associated liver cirrhosis did not show a correlation with the incidence of recurrence. According to Akaike's Information Criteria (AIC), tumor number is useful for predicting early prognosis, and capsular infiltration is a good indicator of long-term survival. However, portal involvement gives much prognostic information throughout the entire postoperative period. PMID- 1310435 TI - Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis. A study on 207 patients. AB - In 207 cirrhotic patient carriers of hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) was administered with ultrasound guidance. The patients were classified as Child's Class A, 136; B, 54; and C, 17. Their mean age was 63.5 years, and the male-female ratio was 3.5:1. There was a single HCC less than 5 cm in diameter in 162 patients; 45 had more than one HCC. The follow-up ranged from 5 to 71 months (mean, 25 months). No noteworthy complications occurred during or after 2485 treatments. The 1-year, 2-year, and 3-year survival percentages (by the Kaplan-Meier method) for the patients with one HCC were 90%, 80%, and 63%, respectively. The corresponding percentages by Child's class were 97%, 92%, and 76% for Class A; 88%, 68%, and 42% for B; and 40%, 0%, and 0% for C. The 1-year, 2-year and 3-year survival rates for patients with more than one HCC were 90%, 67%, and 31% respectively. These results were similar to those found by others and showed that PEI was a safe, reproducible, easy-to-do, and low cost therapeutic technique. In terms of survival, these PEI results were better than the published results of no treatment and equivalent to those of surgery. In uncontrolled series, bias can play an important role. Therefore, additional trials would be useful. PMID- 1310436 TI - Treatment of malignant fibrous histiocytoma of the heart. AB - Primary soft tissue sarcoma of the heart is encountered infrequently in clinical practice. Treatment is reported of an intracardiac malignant fibrous histiocytoma, consisting of maximal surgical resection followed by 5600 cGy of conventionally fractionated radiation therapy. Transesophageal echocardiograms done during follow-up were useful in assessing tumor control. Aspects of patient care are discussed in conjunction with a review of the available literature. PMID- 1310437 TI - Placental-like alkaline phosphatase and DNA flow cytometry in spermatocytic seminoma. AB - Immunohistochemical analysis was done on 7 testicular tumors classified as spermatocytic seminoma (SS) and 25 classic seminomas. Except for a few scattered cells, the spermatocytic seminomas were negative for placental-like alkaline phosphatase (PLAP); the classic seminomas were all positive for this enzyme. The SS also were negative for alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (hCG), and leukocyte common antigen (LCA). The ploidy of the seven tumors of SS was as follows: two, diploid; two, near-diploid; one, tetraploid; one, aneuploid; and one, uninterpretable. The essentially negative staining of SS for PLAP was strikingly different from the pattern in classic seminoma. Thus, staining for this enzyme is useful for making the differential diagnosis between classic seminoma and SS. To differentiate between malignant lymphoma and SS, staining for leukocyte common antigen is helpful. PMID- 1310440 TI - Structure and possible functions of the calcospherite-rich cells (R* cells) in the digestive gland of the shore crab Carcinus maenas. AB - R*-cells of the digestive gland of Carcinus maenas have been investigated functionally and morphologically. A comparison of the capacity of separated cell suspensions to synthesize glycogen gave support to the hypothesis that R and R* cells belong to the same cell line. The unexpected observation of R* cells in gastric juice suggests that their release could represent a mode of redistribution of carbohydrate stores when the feeding activity of the crab is lower. Under electron microscopy, the calcospherites of R* cells appeared to be surrounded by multiple membranous layers, and displayed tubular and vesicular structures in their core. High glucose-6-phosphatase (G6Pase) activity in the subcellular fraction that is enriched in calcospherites suggests that these membranes are derived from the endoplasmic reticulum, via a process in which the enzyme plays a key role. We propose that this is the way by which the R cell differentiates into R* cell. PMID- 1310441 TI - Differentiation of the melanotrophic cells of rat pituitary primordium in organotypic culture in defined medium. AB - Organotypic cultures, in defined medium, of pituitary primordia obtained from 15 day-old rat fetuses were performed in order to study the in vitro differentiation of melanotrophic cells. The morphological and ultrastructural features of the transplants resembled those of the gland developing in vivo. In situ hybridization on semi-thin sections, using a 35S-labelled oligonucleotide probe, revealed pro-opiomelanocortin-mRNA-containing cells on the first day of culture in the anterior lobe and after 2-3 days in the intermediate lobe. Immunoperoxidase labelling of adjacent sections showed that the same cells reacted with antibodies against alpha-melanocyte-stimulating hormone (alpha MSH), gamma 3MSH and adrenocorticotropic hormone in both lobes. The pro opiomelanocortin-mRNA-containing cells formed progressively conspicuous areas in the intermediate lobe, which was almost uniformly labelled after 6 days. In the anterior lobe, these cells remained scattered in small cell groups, and colloidal gold immunolabelling showed the progressive disappearance of alpha MSH labelling from the secretory vesicles in cells exhibiting morphological features of adult corticotrophic cells. Both the alpha MSH content of the explants and alpha MSH release into the culture medium increased with time. Treatment with the dopamine agonist bromocriptine induced a strong dose-dependent decrease in alpha MSH secretion, which was significant after 3 days in culture, indicating that dopamine D2 receptors are able to regulate hormonal release of melanotrophic cells at early stages. This system constitutes a suitable model for further studies of factors controlling cell differentiation and cellular interactions involved in histogenesis. PMID- 1310442 TI - Identification of skeletal muscle precursor cells in vivo by use of MyoD1 and myogenin probes. AB - The activation of mononuclear muscle precursor cells after crush injury to mouse tibialis anterior muscles was monitored in vivo by in situ hybridization with MyoD1 and myogenin probes. These genes are early markers of skeletal muscle differentiation and have been extensively studied in vitro. The role in vivo of these regulatory proteins during myogenesis of mature muscle has not been studied previously. MyoD1 and myogenin mRNA were present in occasional mononuclear cells of uninjured muscle. Increased MyoD1 and myogenin mRNA sequences in mononuclear cells were detected as early as 6 h after injury, peaked between 24 and 48 h, and thereafter declined to pre-injury levels at about 8 days. The mRNAs were detected in mononuclear cells throughout the muscle, with the majority of cells located some distance from the site of crush injury. The presence of MyoD1 and myogenin mRNA at 6 to 48 h indicates that transcription of these genes is occurring at the same time as replication of muscle precursor cells in vivo. At no time were significant levels of mRNA for these genes detected in myotubes. MyoD1 and myogenin provide precise markers for the very early identification and study of mononuclear skeletal muscle precursor cells in muscle regenerating in vivo. PMID- 1310438 TI - Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. AB - Studies of the pathogenesis and molecular biology of JC virus infection over the last two decades have significantly changed our understanding of progressive multifocal leukoencephalopathy, which can be described as a subacute viral infection of neuroglial cells that probably follows reactivation of latent infection rather than being the consequence of prolonged JC virus replication in the brain. There is now sufficient evidence to suggest that JC virus latency occurs in kidney and B cells. However, JC virus isolates from brain or kidney differ in the regulatory regions of their viral genomes which are controlled by host cell factors for viral gene expression and replication. DNA sequences of noncoding regions of the viral genome display a certain heterogeneity among isolates from brain and kidney. These data suggest that an archetypal strain of JC virus exists whose sequence is altered during replication in different cell types. The JC virus regulatory region likely plays a significant role in establishing viral latency and must be acted upon for reactivation of the virus. A developing hypothesis is that reactivation takes place from latently infected B lymphocytes that are activated as a result of immune suppression. JC virus enters the brain in the activated B cell. Evidence for this mechanism is the detection of JC virus DNA in peripheral blood lymphocytes and infected B cells in the brains of patients with progressive multifocal leukoencephalopathy. Once virus enters the brain, astrocytes as well as oligodendrocytes support JC virus multiplication. Therefore, JC virus infection of neuroglial cells may impair other neuroglial functions besides the production and maintenance of myelin. Consequently our increased understanding of the pathogenesis of progressive multifocal leukoencephalopathy suggests new ways to intervene in JC virus infection with immunomodulation therapies. Perhaps along with trials of nucleoside analogs or interferon administration, this fatal disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols. PMID- 1310443 TI - Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. AB - Single or multiple brief periods of ischemia (preconditioning) have been shown to protect the myocardium from infarction after a subsequent more prolonged ischemic insult. To test the hypothesis that preconditioning is the result of opening ATP sensitive potassium (KATP) channels, a selective KATP channel antagonist, glibenclamide, was administered before or immediately after preconditioning in barbital-anesthetized open-chest dogs subjected to 60 minutes of left circumflex coronary artery (LCX) occlusion followed by 5 hours of reperfusion. Preconditioning was elicited by 5 minutes of LCX occlusion followed by 10 minutes of reperfusion before the 60-minute occlusion period. Glibenclamide (0.3 mg/kg i.v.) or vehicle was given 10 minutes before the initial ischemic insult in each of four groups. In a fifth group, glibenclamide was administered immediately after preconditioning. In a final series (group 6), a selective potassium channel opener, RP 52891 (10 micrograms/kg bolus and 0.1 micrograms/mg/min i.v.) was started 10 minutes before occlusion and continued throughout reperfusion. Transmural myocardial blood flow was measured at 30 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percent of the area at risk. There were no significant differences in hemodynamics, collateral blood flow, or area at risk between groups. The ratio of infarct size to area at risk in the control group (28 +/- 6%) was not different from the group pretreated with glibenclamide in the absence of preconditioning (31 +/- 6%). Preconditioning produced a marked reduction (p less than 0.002) in infarct size (28 +/- 6% to 6 +/- 2%), whereas glibenclamide administered before or immediately after preconditioning completely abolished the protective effect (28 +/- 6% and 30 +/- 8%, respectively). RP 52891 also produced a significant (p less than 0.03) reduction (28 +/- 6% to 13 +/- 3%) in infarct size. These results suggest that myocardial preconditioning in the canine heart is mediated by activation of KATP channels and that these channels may serve an endogenous myocardial protective role. PMID- 1310444 TI - Atrial and brain natriuretic peptides inhibit the endothelin-1 secretory response to angiotensin II in porcine aorta. AB - We have recently shown that the porcine aorta releases immunoreactive endothelin 1 in a time-dependent way. Here, we examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion after stimulation with angiotensin II (Ang II) by using porcine aorta. Ang II dose dependently stimulated immunoreactive endothelin-1 secretion. Porcine ANP-(1-28) and porcine BNP-26 both inhibited such secretion in a dose-dependent way. The addition of a cyclic guanosine 5'-monophosphate (cGMP) analogue, 8-bromo-cGMP, reduced the immunoreactive endothelin-1 secretion after stimulation with Ang II. In cultured porcine endothelial cells the inhibition by porcine ANP-(1-28) and porcine BNP-26 of immunoreactive endothelin-1 secretion after stimulation with Ang II was paralleled by an increase in the cellular cGMP level. Rat ANP-(5-25) was weaker than porcine ANP-(1-28) in inhibiting immunoreactive endothelin-1 secretion and increasing cGMP in cultured cells. There was negative correlation between the percent decrease in immunoreactive endothelin-1 and the percent increase in cGMP. Neither porcine ANP-(1-28) nor BNP-26 affected the number or sensitivity of Ang II binding sites in cultured porcine endothelial cells. These results suggest that ANP and BNP inhibit endothelin-1 secretion after stimulation with Ang II, probably through a cGMP-dependent process. PMID- 1310439 TI - New aspects of influenza viruses. AB - Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands. PMID- 1310445 TI - Reduced production of cGMP underlies the loss of endothelium-dependent relaxations in the canine basilar artery after subarachnoid hemorrhage. AB - Endothelium-dependent relaxations are inhibited during chronic vasospasm after subarachnoid hemorrhage in the canine basilar artery, although the luminal release of endothelium-derived relaxing factor (EDRF) is maintained. The present study investigated the mechanisms underlying the impaired vascular reactivity and in particular whether the loss of responsiveness of the smooth muscle to EDRF is due to an impaired production of cGMP. Bradykinin and nitric oxide evoked concentration-dependent relaxations in isolated canine basilar arteries with and without endothelium, respectively, which were reduced in the subarachnoid hemorrhage group. Relaxations evoked by M&B22,948 (an inhibitor of cGMP phosphodiesterases) were smaller, but those evoked by the lipophilic cGMP analogue 8-bromo-cGMP were potentiated slightly in the subarachnoid hemorrhage group. The resting levels of cGMP in rings with endothelium (reflecting the effect of spontaneous release of EDRF) and those evoked by bradykinin in rings with endothelium and by nitric oxide in rings without endothelium were diminished in the subarachnoid hemorrhage group. These data indicate that the altered endothelium-mediated relaxations of the smooth muscle after subarachnoid hemorrhage is due, at least in part, to an impaired activation of soluble guanylate cyclase leading to a reduced production of cGMP in the smooth muscle. PMID- 1310446 TI - Characterization of acetylcholine-induced membrane hyperpolarization in endothelial cells. AB - The characteristics of the hyperpolarization response to acetylcholine (ACh) in endothelial cells from the guinea pig coronary artery were studied by microelectrode recording technique. ACh (30 nM to 3 microM) induced membrane hyperpolarization in a dose-dependent manner. The sustenance of the response required the presence of external calcium. The hyperpolarization was not affected by nifedipine (1 microM) but was inhibited by the potassium channel blockers charybdotoxin (10 nM), tetraethylammonium (1 mM), and 4-aminopyridine (0.5 mM). Glibenclamide (10 microM) and apamin (1 microM) were not effective. The inhibitors of endothelium-derived relaxing factor/nitric oxide synthesis N omega nitro L-arginine (50 microM) and NG-monomethyl L-arginine (30 microM) had no effect on the resting membrane potential or the ACh-induced responses. No hyperpolarization was observed with application of sodium nitroprusside (10 microM) or 8-bromo-cGMP (0.1 microM). Ouabain (10 microM) depolarized the membrane significantly by 5 mV, but the ACh hyperpolarization was not affected. Indomethacin (10 microM) was without effect on the resting membrane potential or the hyperpolarization to ACh. These results show that ACh-induced hyperpolarization is dependent on external calcium and can be inhibited by certain potassium channel blockers. The hyperpolarization response is not mediated by endothelium-derived relaxing factor/nitric oxide, cGMP, a cyclooxygenase product, or stimulation of the Na-K pump. PMID- 1310447 TI - Vascular bound recombinant extracellular superoxide dismutase type C protects against the detrimental effects of superoxide radicals on endothelium-dependent arterial relaxation. AB - Extracellular superoxide dismutase type C (EC-SOD C) is a secretory SOD isoenzyme that, in vivo, is bound to heparan sulfate proteoglycans in the glycocalyx of various cell types (e.g., endothelial cells) and in the connective tissue matrix. The aim of this study was to investigate the efficacy of vascular bound EC-SOD C in protecting arterial relaxation mediated by endothelium-derived relaxing factor (EDRF) against the inhibitory effects of superoxide radicals. For comparison, the effect of CuZn SOD was also studied. This SOD isoenzyme lacks affinity toward heparan sulfate and does not bind to cell surfaces. Rings from rabbit aorta were mounted in an organ bath and acetylcholine-induced endothelium-dependent relaxation was then studied in preparations precontracted with phenylephrine. Pyrogallol (10(-4) M), used to generate superoxide radicals, reduced the maximal relaxant effect of acetylcholine from about 65% to 25%. When present in the buffer throughout the experiment, CuZn SOD and EC-SOD C caused a concentration dependent prevention of the pyrogallol effect on EDRF-mediated relaxation, with a half-maximal effect at about 100 units/ml (KO2 assay). In a second set of experiments, the arterial rings were preincubated with 8,000 units/ml CuZn SOD (50 micrograms/ml) or EC-SOD C (69 micrograms/ml) during 30 minutes, followed by washing, before the effect of pyrogallol on EDRF-mediated relaxation was studied in SOD-free buffer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310448 TI - Effects of oxidant stress on endothelium-derived relaxing factor-induced and nitrovasodilator-induced cGMP accumulation in vascular cells in culture. AB - The effects of hydrogen peroxide (H2O2) on the action of basally produced endothelium-derived relaxing factor (EDRF) were investigated by measuring cGMP accumulation in single and cocultures of calf pulmonary artery endothelial cells (CPAEs) and rabbit pulmonary artery smooth muscle cells (RPASMs) as a model for determining the contribution of EDRF dysfunction to altered vascular tone and reactivity frequently associated with oxidant-induced vascular injury. Higher cGMP levels in long-term cocultures (20.4 +/- 1.8 pmol/mg protein/15 min) than in single-cell cultures (CPAE, 9.6 +/- 0.9 pmol/mg protein/15 min; RPASM, 3.7 +/- 0.2 pmol/mg protein/15 min), and CPAE-induced increases (fivefold) in intracellular RPASM cGMP content in short-term cocultures suggest basal release of EDRF. Basal generation and release of an L-arginine-derived endothelial labile factor accounted for the increases in cGMP, since the response was completely blocked by pretreatment of CPAEs with NG-monomethyl L-arginine. Pretreatment of long-term cocultures with H2O2 for 30 minutes resulted in a dose-dependent (0.5-2 mM) decrease in cGMP formation (49-79%). To determine the effects of H2O2 on EDRF synthesis, transport, and RPASM responsiveness, CPAEs or RPASMs were selectively pretreated with H2O2 before establishment of short-term cocultures. In cocultures of H2O2-pretreated CPAEs with untreated RPASMs, RPASM cGMP levels were reduced, suggesting a decrease in EDRF production rather than deterioration of EDRF during transport, because cGMP levels were unaffected by posttreatment with oxygen radical scavengers during coculture. Pretreatment of RPASMs with H2O2 attenuated the untreated CPAE-induced, the putative EDRF S-nitroso-L-cysteine-induced, or the nitroprusside-induced increases in RPASM cGMP levels. This attenuation was prevented by pretreatment with either dimethylthiourea, deferoxamine, or dithiothreitol, suggesting a mechanism of H2O2 action involving iron-catalyzed formation of intracellular hydroxyl radicals and their attack on cellular thiols. H2O2 diminution of cGMP accumulation was not associated with lytic cell injury in the experimental time frame, because morphology and 51Cr release from prelabeled RPASMs and CPAEs were unchanged. PMID- 1310449 TI - Capillary hydraulic conductivity is elevated by cGMP-dependent vasodilators. AB - Microvascular functions have been shown to be sensitive to agents associated with changes in cyclic nucleotide levels. The central hypothesis of the current study was that one measure of capillary exchange capacity, hydraulic conductivity (Lp), would be elevated by agents shown to elevate cellular levels of cGMP. To evaluate the hypothesis, frog mesenteric capillary Lp was measured during luminal exposure to 1) atrial natriuretic peptide (ANP), 2) the truncated atriopeptins ANP-I and ANP-III, 3) the nitrovasodilator sodium nitroprusside (SNP), 4) the cGMP phosphodiesterase inhibitor M&B 22948, and 5) methylene blue dye, both alone and in combination with ANP or SNP. ANP (100 nM) elevated Lp by 2.3 +/- 0.2-fold from control levels (n = 15); 10 nM ANP induced a 2.1 +/- 0.3-fold change (n = 8), while 10 nM ANP-III elicited a 1.7 +/- 0.4-fold change (n = 8). In contrast, Lp did not change from basal levels during 10 nM ANP-I infusion (Lp ANP-I/Lp control = 1.2 +/- 0.2; n = 14). SNP (1 microM) induced a reversible, 2.6 +/- 0.5-fold increase in Lp (n = 30) that was inhibitable by methylene blue dye (Lp SNP + MetB/Lp control = 1.1 +/- 0.1; n = 8). Methylene blue did not mask the response to 100 nM ANP (Lp ANP + MetB/Lp control = 2.1 +/- 0.5; n = 7). M&B 22948 (30 microM) increased Lp by 2.8 +/- 0.6-fold (n = 9). These data constitute strong inference that agents demonstrated to elevate cGMP also mediate an increase in capillary Lp in in situ, perfused exchange vessels. PMID- 1310450 TI - Cardiac myocytes express multiple gap junction proteins. AB - Electrical propagation in the normal heart occurs via intercellular transfer of current at gap junctions. Alterations in intercellular coupling in the diseased heart are critical in the pathogenesis of reentrant ventricular arrhythmias. Until recently only a single gap junction protein was known to couple cardiac myocytes. We have now identified and sequenced two additional distinct gap junction proteins (connexins) expressed in the mammalian heart. The sequences differ in their predicted cytoplasmic regulatory domains. Expression of all three connexins by canine ventricular myocytes has been confirmed by Northern blotting and by immunohistochemistry with connexin-specific antisera. Immunoelectron microscopy confirmed that all three connexins are localized to myocyte gap junctions. The presence of multiple connexins in myocyte gap junctions suggests novel mechanisms for regulating cardiac electrical coupling. PMID- 1310451 TI - A low-sodium diet corrects the defect in beta-adrenergic response in older subjects. AB - BACKGROUND: One of the prominent cardiovascular abnormalities in the elderly is reduced beta-adrenoceptor responsiveness. Because dietary sodium restriction corrects the defect in vascular and lymphocyte beta-adrenoceptor responsiveness in hypertensive subjects, we postulated an analogous effect in the elderly. Thus, vascular and lymphocyte beta-adrenergic responsiveness were studied in 10 older normotensive subjects (age, 56 +/- 2 years) on either a 400- or 10-meq/day sodium diet. METHODS AND RESULTS: In older subjects fed a high-sodium diet, maximal isoproterenol-mediated vasodilation was depressed compared with a group of normotensive younger subjects studied previously. When they were fed a low-sodium diet, however, maximal isoproterenol-mediated vasodilation in the elderly was increased significantly. Lymphocyte adenylyl cyclase sensitivity to isoproterenol was comparably increased. Blood pressure was significantly reduced on a low sodium diet, and mean arterial pressure was significantly inversely correlated with the extent of isoproterenol-mediated vasodilation. CONCLUSIONS: These studies indicate that a low-sodium diet corrects the defect in both vascular and lymphocyte beta-adrenergic responsiveness with aging. This suggests an important role for dietary modification in the adrenergic regulation of vascular tone in the elderly. PMID- 1310452 TI - Myocardial adrenergic denervation supersensitivity depends on a postreceptor mechanism not linked with increased cAMP production. AB - BACKGROUND: Two major hypotheses have been proposed to explain catecholamine supersensitivity after myocardial denervation, but neither sufficiently explains certain features of the phenomenon. In addition, a nonsurgical method for long term myocardial adrenergic denervation is desirable but has not been accomplished or described with respect to catecholamine supersensitivity. METHODS AND RESULTS: We have accomplished chronic myocardial adrenergic denervation by using 6 hydroxydopamine (6-OHDA). Sixteen weeks after 6-OHDA administration to newborn pigs, we found substantial myocardial adrenergic denervation associated with beta adrenergic receptor (beta AR) downregulation. Despite decreased beta AR number, the dose of isoproterenol yielding 50% maximal heart rate change (ED50) was decreased, and heart rates during exercise showed increased responsiveness despite decreased circulating catecholamines. Thus, stimulation of fewer receptors yielded an increased response, implying improved signal transduction efficiency. Competitive binding studies with isoproterenol showed an increased proportion of beta AR with high-affinity binding in myocardial membranes from 6 OHDA pigs, suggesting that interaction between beta AR and cardiac G, may contribute to improved signal transduction efficiency. However, measures of adenylyl cyclase activity indicated marked reduction in beta AR-dependent and G2 dependent cAMP production in myocardial membranes from denervated animals despite a normal amount of cardiac Gs and decreased Gi. CONCLUSIONS: We have demonstrated that substantial, long-term myocardial adrenergic denervation is possible using 6 OHDA. Denervation supersensitivity in this model does not depend on enhanced cAMP stimulation but rather depends on postreceptor elements in the beta AR-responsive pathway that may be independent of Gs-activated adenylyl cyclase activity. In this model of adrenergic denervation supersensitivity, beta-receptors, through Gs, may be linked to an alternative effector that drives heart rate responsiveness. PMID- 1310453 TI - Variable gene usage of T cell receptor gamma- and delta-chain transcripts expressed in synovia and peripheral blood of patients with rheumatoid arthritis. AB - The synovial tissue and fluid of patients with rheumatoid arthritis (RA) contain activated T cells that probably have a central role in the disease process which leads to joint destruction. A subset of T cells, gamma delta T cells detected at the site of inflammation, may be important in the pathogenesis of the disease. This study investigated variable (V) gene usage of gamma delta T cell receptors (TcRs) expressed in synovia and peripheral blood of patients with RA by using the polymerase chain reaction (PCR) to amplify TcR gamma- and delta-chain transcripts. Most patients showed no restriction in V gamma gene usage since synovial mononuclear cells (SMC) expressed TcR gamma-chain transcripts which used the same set of V gamma genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC V delta-chain repertoire biased towards V delta 1, but V delta 2 mRNA transcripts were also detected, albeit at low levels in some patients. The TcR delta-chain repertoires of PBMC from healthy control subjects were also characterized. There was variation in the TcR delta-chain repertoires of PBMC from patients when compared with controls, particularly with respect to expression of V delta 4. V delta 4 mRNA transcripts were expressed in PBMC of only two of seven RA patients in contrast with eight of the nine controls (P = 0.03). These findings are compatible with reports that gamma delta T cells in the rheumatoid synovium are reactive to Mycobacterium tuberculosis and that response to M. tuberculosis is restricted to V gamma 9/V delta 2-bearing T cells, if a superantigen is involved in the pathogenesis of RA. PMID- 1310455 TI - Delayed recognition of a vascular complication, carotid artery aneurysm, 60 years after operation for muscular torticollis. A case report. AB - An extremely rare vascular complication, carotid artery aneurysm, developed 60 years after a torticollis operation. The patient's internal jugular vein was completely obstructed proximal to the subclavian vein. There was an associated incomplete obstruction of the ipsilateral common carotid artery on the right aspect of the neck--the site where resection of the whole sternocleidomastoid muscle had been performed when she was one year old. The patient had audible bruits over the right common carotid at the base of her neck but no signs of occlusive cerebrovascular disease. The diagnosis was made mainly with use of technetium radionuclide angiography. To the authors' knowledge, this is the first such report in the English or German literature. PMID- 1310454 TI - Interaction and intracellular killing of Candida albicans blastospores by human polymorphonuclear leucocytes, monocytes and monocyte-derived macrophages in aerobic and anaerobic conditions. AB - Polymorphonuclear leucocytes (PMN), monocytes and monocyte-derived macrophages were capable of interacting with opsonized C. albicans in both aerobic and anaerobic conditions. Superoxide anion release by these cells was inhibited in anaerobic conditions while lysozyme release and phagocytosis were equally efficient in both aerobic and anaerobic conditions. All cell types tested were capable of intracellular killing of C. albicans and this appeared to be maximum at 6 h for monocytes and macrophages and 24 h for PMN. Monocytes killed the lowest number of organisms, 1 x 10(6), and the killing was similar for aerobic and anaerobic conditions. In contrast, PMN and macrophages demonstrated greater killing of C. albicans in aerobic conditions compared with anaerobic conditions; PMN killed 1.9 x 10(6) organisms and macrophages 3 x 10(6) when incubated anaerobically. Inhibitors of oxygen metabolism decreased intracellular killing of C. albicans by macrophages and PMN in aerobic but not anaerobic conditions. The oxygen reaction products involved in the killing of C. albicans appeared to be different however: macrophage killing was decreased by superoxide anion and hydrogen peroxide inhibitors. PMN killing was decreased by superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radical inhibitors. The present study shows that although monocytes, macrophages and PMN function similarly in their interaction with C. albicans, they appear to use different oxygen reactive products for the intracellular killing of C. albicans. PMID- 1310456 TI - Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Bioassay by histamine bronchoprovocation. AB - The results of previous studies comparing bronchodilatation from beta agonists administered by metered-dose inhaler (MDI) and nebulizer solution have been conflicting. We therefore evaluated a range of albuterol doses administered by these two methods, using histamine bronchoprovocation as a bioassay for the amount of drug reaching the beta 2 receptors in the lung. Twelve stable asthmatic volunteers received, in a double-blind, randomized, crossover design on different days, placebo or one, two, four, or six puffs from an MDI attached to an InspirEase device (90 micrograms per puff) or 0.625, 1.25, 2.5, or 5.0 mg of solution delivered in 2 ml of buffered saline through a Hudson Updraft II nebulizer. The histamine concentration required to decrease FEV1 by 20 percent (PC20) was measured 1 h before and 30 min after administration of each treatment and expressed as the increase in PC20 from baseline. The dose-response curves for change in PC20 indicated that the higher doses of the nebulizer solution delivered more drug to beta 2 receptors in the lung than the lower doses from the MDI. For example, the geometric mean increase in PC20 was 1.1 +/- 1.6 (SD) after placebo, 7.5 +/- 2.7 after two puffs from the MDI, and 20.0 +/- 2.1 after 2.5 mg of nebulizer solution (p less than 0.05). Using this bioassay method and administration technique, we estimated that ten puffs from the MDI (0.9 mg) would deliver approximately the same amount of albuterol to lung receptors as 2.5 mg of the nebulizer solution. Taking into account previously published reports and the results of the present study, we conclude that differences in dose, administration technique, nebulizer system efficiency, and severity of airway obstruction can alter the amount of drug reaching the beta 2 receptors in the lungs and, thus, the clinical response. PMID- 1310457 TI - Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis. AB - The pathogenesis of oxygen toxicity remains unknown but may involve leukocyte mediated injury. The effects of hyperoxia on several lower respiratory tract parameters were examined in bronchoalveolar lavage fluid of normal nonsmoking subjects who inhaled a fractional inspired oxygen concentration of 50 percent (mean exposure: 44 h). Evidence that 50 percent O2 produced oxidative stress in the lung included recovery of fluorescent products of lipid peroxidation and partial oxidation of alpha 1-antitrypsin in BAL fluid obtained after O2 exposure. To examine whether alveolar macrophage-derived leukotriene B4 may be generated in response to 50 percent O2, AM were isolated from O2-exposed subjects and compared with AM recovered from subjects breathing room air. Leukotriene B4 levels were elevated in supernatants from both unstimulated and arachidonic acid-stimulated AM obtained from hyperoxia-exposed subjects. In hyperoxia-exposed individuals, LTB4 levels were also elevated in extracted BAL fluid. The percentage of BAL neutrophils was also significantly increased after O2 exposure (2.8 +/- 0.6 vs 1.2 +/- 0.4 percent, p = 0.05). We conclude that an FIO2 of 50 percent inhaled for 44 h is associated with enhanced oxidative stress, stimulation of AM to release LTB4, and a small but significantly increased percentage of neutrophils recovered in BAL fluid. PMID- 1310458 TI - Bilateral multiple sclerosing hemangiomas of the lung. AB - A Chinese woman had bilateral coin lesions of the lung, which grew slowly. At pathologic examination, the lesions were considered to be multiple sclerosing hemangiomas. Multiplicity is rare, and bilaterality has not been previously reported. PMID- 1310459 TI - Alterations in quantitative distribution of Na,K-ATPase activity along crypt villus axis in animal model of malabsorption characterized by hyperproliferative crypt cytokinetics. AB - The distribution of sodium- and potassium-stimulated ATPase (Na,K-ATPase) along the crypt-villus axis and crypt cytokinetics were examined in an infective model of celiac disease produced by infection of the rat with the nematode Nippostrongylus brasiliensis. In controls, levels of enzyme activity remained stable during enterocyte migration to the villous apex. In the jejunum of infected rats, the structural lesion of villous atrophy and crypt hyperplasia, observed at day 10 of infection, was associated with a three-dimensional expansion of the crypts. Cell cycle time was shortened and this resulted in a markedly increased crypt cell production rate. Enterocytes emerged from the crypts at a faster rate, and this functional immaturity was paralleled by decreased Na,K-ATPase activity. Further decreases in enzyme levels were observed during enterocyte migration along the villi. This may reflect enterocyte damage or increased enzyme turnover. In the ileum of these animals, enterocyte maturation was prolonged and enzyme activity was increased at the level of the crypt villus junction with further increases noted during enterocyte transit. These changes in ileal Na,K-ATPase appear to be adaptive. PMID- 1310460 TI - Activation of hepatitis C virus following immunosuppressive treatment. PMID- 1310461 TI - [Intestinal osteopathy following partial gastric resection]. AB - 26 years after a partial gastric resection (Billroth II) for recurrent gastric ulcer a 62-year-old man developed severe intestinal osteopathy. For three years he had increasing pain in the lower back and hip with a noticeable waddling gait. Serum concentration of calcium (2.0 mmol/l) and 25-hydroxy-vitamin D3 (38 mmol/l) were reduced, those of alkaline phosphatase (572 U/l) and parathormone (532 pg/ml) increased. Radiology demonstrated Looser's zones in the ribs and iliac crest. Osteodensitometry showed obviously diminished bone density. Iliac crest biopsy revealed signs of osteomalacia and secondary hyperparathyroidism. Within three months of starting oral vitamin D3 and calcium the symptoms had definitely receded and serum concentrations of calcium and alkaline phosphatase had become normal (2.4 mmol/l and 156 U/l, respectively). Osteopathic symptoms are often the expression of an abnormal calcium/phosphate metabolism. The cause often lies in the gastrointestinal tract; not rarely it is a late complication of a gastrojejunostomy. PMID- 1310462 TI - [Malignant fibrous histiocytoma of the aorta]. AB - Upper gastrointestinal bleeding occurred in a 64-year-old woman who was being treated with 1,000 mg acetylsalicylic acid and three times 5,000 IU heparin daily previous to a planned embolectomy because of occlusion of a lower leg artery. Radiology demonstrated multiple areas of osteolysis of the left thorax which were interpreted as recurrence of carcinoma of the breast, treated by mastectomy and radiotherapy 15 years previously. Acute renal failure, recurring severe back and abdominal pain, paraplegia of both legs and finally death from circulatory failure were explained as having been caused by multiple embolisation in the course of arteriosclerosis or a paraneoplastic increase in clotting activity. Autopsy revealed complete occlusion of the descending thoracic aorta by a malignant fibrous histiocytoma which had been the site of multiple emboli of thrombotic material and tumour tissue to spleen, kidneys, liver, intestinal segments, spinal cord and the artery to the left lower leg. Adrenal metastasis and osteolysis of the ribs were due to the histiocytoma and not the previously known carcinoma of the breast. PMID- 1310463 TI - [Transforming growth factor beta: its mechanism of action and clinical significance]. PMID- 1310464 TI - Clinical evaluation of different doses of pipecuronium bromide during nitrous oxide-fentanyl anaesthesia in adult surgical patients. AB - The neuromuscular and cardiovascular effects of three different doses of pipecuronium were studied in 60 adult patients. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 0.1 Hz and 2 Hz. Three subgroups (A, B, C) of 20 patients received pipecuronium doses of 60, 80 and 100 micrograms kg-1, respectively, as an intubating dose and, when necessary, maintenance doses were administered at 25% single twitch recovery in a dose of one-quarter of the initial one. The onset time was 5.4 +/- 2.0 min for 60 micrograms kg-1 and similar for 80 and 100 micrograms kg-1 (3.9 +/- 1.1 and 3.6 +/- 1.1 min). The duration of action was 45 +/- 10 min for 60 micrograms kg-1, 74 +/- 25 and 94 +/- 21 for 80 and 100 micrograms kg-1, respectively. The recovery indices were measured in all patients after neostigmine administration (Groups B and C) and after neostigmine and edrophonium (Subgroup A, 10 patients each). TOF ratio was significant only 2 min after edrophonium administration in Group A patients. Variations of heart rate and blood pressure were not significant. PMID- 1310465 TI - The influence of isoflurane on peri-operative endocrine and metabolic stress responses. AB - Trauma and surgery profoundly affect the circulating concentrations of metabolites and so-called stress hormones, and may thereby directly or indirectly influence recovery. This stress response on the other hand is subject to modification by the anaesthetics employed. We investigated the effects of isoflurane on selected stress parameters in 10 patients undergoing major abdominal surgery and compared them to those in 10 patients receiving halothane. Plasma levels of adrenaline, noradrenaline, cortisol, ACTH, and beta-endorphin, as well as glucose, non-esterified fatty acids (NEFA), and lactate were determined during a pre-operative anaesthesia period as well as intra- and post operatively. The levels of all parameters remained stable or decreased during the pre-operative anaesthesia period. They increased intra- and/or post-operatively, reaching peak values in the recovery period. Although the changes in both groups were basically similar, we observed lower serum concentrations of cortisol and lactate in the isoflurane group. We conclude that isoflurane and halothane have similar effects on peri-operative changes of endocrine and metabolic parameters, and that neither can effectively block the stress response to major surgery. We found no firm evidence for a stimulatory effect of isoflurane on the parameters studied. PMID- 1310466 TI - Interaction between the cell-cycle-control proteins p34cdc2 and p9CKShs2. Evidence for two cooperative binding domains in p9CKShs2. AB - A universal intracellular factor, the 'M-phase-promoting factor' (MPF), displaying histone H1 kinase activity and constituted of at least two subunits, p34cdc2 and cyclin Bcdc13, triggers the G2----M transition of the cell cycle in all organisms. The yeast p13suc1 and p18CKS1 subunits and their functionally interchangeable human homologues, p9CKShs1 and p9CKShs2, directly interact with p34cdc2 and may actually be part of the MPF complex. We have chemically synthesized p9CKShs2 and several of its peptide domains in order to investigate the binding of p9CKShs2 and p34cdc2. Several arguments support the hypothesis that the N-terminal half (peptide B) and the C-terminal half (peptide E) each contain a p34cdc2-binding site and that these two binding domains cooperate in establishing a stable p9CKShs2-p34cdc2 complex: (a) only the combination of peptides B + E, and not B or E alone, is able to elute the cdc2 kinase from p9CKShs1-Sepharose beads; (b) only immobilized peptides B + E, and not immobilized B or E, bind the cdc2 kinase; (c) only the peptides B + E combination, and not B or E alone, can compete with p9CKShs1 for cdc2 kinase binding; (d) only when supplemented with E or B free peptide does the cdc2 kinase bind to B- or E-Sepharose beads, respectively. No binding occurs in the absence of free peptide. This additivity cannot be attributed to the formation of a B-E complex mimicking the full-length p9CKShs2. The cyclin B subunit is not required for the formation of the p9CKShs2-p34cdc2 complex through these two binding domains. The implications of the existence of two cooperative p34cdc2-binding domains in p9CKShs2 on the structure of the active M-phase-specific kinase is discussed. PMID- 1310467 TI - Thermodynamics of interaction of a fluorescent DNA oligomer with the anti-tumour drug netropsin. AB - Fluorescence spectroscopy was used to study the interaction between the minor groove-binding drug netropsin and the self-complementary oligonucleotide d(CTGAnPTTCAG)2 containing the fluorescent base analogue 2-aminopurine (nP). The binding of netropsin to this oligonucleotide causes strong quenching of the 2 aminopurine fluorescence, observed by steady-state as well as time-resolved spectroscopy. From fluorescence titrations, binding isotherms were recorded and evaluated. The parameters showed one netropsin binding site/oligonucleotide duplex and an association constant of about 10(5) M-1 at 25 degrees C, 3-4 orders of magnitude weaker than for an exclusive adenine/thymine host sequence. From the temperature dependence of the association constant the thermodynamic parameters were obtained as delta G = -29 kJ/mol, delta H = -12 kJ/mol and delta S = +55 J.mol-1.K-1 at 25 degrees C. These parameters resemble those of the interaction of poly[(dG-dC).(dG-dC)] with netropsin, indicating a mainly entropy-driven reaction. The amino group of 2-aminopurine, like that of guanine, resides in the minor groove of DNA. Therefore the relatively weak binding of netropsin to d(CTGAnPTTCAG)2 is probably related to partial blockage of the tight fit of netropsin into the preferred minor groove of an exclusive adenine/thymine host sequence. PMID- 1310468 TI - Drosophila acetylcholinesterase. Expression of a functional precursor in Xenopus oocytes. AB - In insects, acetylcholinesterase is mainly found in the central nervous system. It is expressed in the synapse where it hydrolyzes the neurotransmitter acetylcholine. Maturation of this protein involves several post-translational modifications. The precursor polypeptide is cut at three sites; the N-terminal signal peptide is removed, the C-terminal hydrophobic polypeptide is clipped off and replaced by a glycolipid anchor and the resulting peptide is cut into two polypeptides, corresponding to active subunits. Two of these active subunits are associated to form the final active glycosylated protein. We have expressed the protein via microinjection of an expression vector into Xenopus oocyte nuclei. When the complete cDNA is injected, the acetylcholinesterase formed is biochemically similar to the Drosophila-head acetylcholinesterase. However, the hydrophobic C-terminal peptide is not replaced by a glycolipid anchor. As a consequence, the enzyme is no longer externalized, the proteolytic cutting of the main peptide does not occur and a new polymerization form occurs. Although incompletely processed, this protein is enzymatically active. When a cDNA lacking the coding region of the C-terminal hydrophobic peptide is injected, the resulting acetylcholinesterase is hydrophilic, cleaved into two subunits and secreted into the incubation medium free of contaminants. PMID- 1310469 TI - Inducible expression of human phospholipase C-gamma 2 and its activation by platelet-derived growth factor B-chain homodimer and platelet-derived growth factor A-chain homodimer in transfected NIH 3T3 fibroblasts. AB - Growth factors such as platelet-derived growth factor (PDGF) have been shown to activate phospholipase C-gamma 1 (PLC-gamma 1). We have overexpressed the human PLC-gamma 2 (hPLC-gamma 2) cDNA in murine NIH 3T3 fibroblasts using the interferon-type-I inducible murine Mx promoter. Northern blot analysis revealed an induction of hPLC-gamma 2 mRNA by interferon (IFN) alpha of about 25-fold as compared to the uninduced transcript level. Western blot analysis with anti(bovine PLC-gamma 2) antiserum showed increased hPLC-gamma 2 protein levels in hPLC-gamma 2 transfected cells. Induction with IFN alpha resulted only in a slight further increase. After labelling the cells with [35S]methionine an increase of radioactive label in a protein migrating at 148 kDa could be detected in IFN-alpha-stimulated, hPLC-gamma 2 overexpressing cells. PLC activity in homogenates from hPLC-gamma 2 overexpressing cells was increased as compared to control cells transfected with the vector lacking the hPLC-gamma 2 cDNA insert. There was no difference between in vitro PLC activity in homogenates from PDGF B chain homodimer (BB) treated and untreated cells. PLC activity was mainly present in the soluble fraction. After incubation of hPLC-gamma 2 overexpressing cells with IFN alpha, the in vitro activity of PLC increased significantly in the soluble fraction. Stimulation with PDGF BB increased inositol phosphate production about 3.5-fold in control cells and about 10-fold in hPLC-gamma 2 overexpressing cells. PDGF A-chain homodimer (AA) showed slightly smaller effects. These results demonstrate that human PLC-gamma 2 can be expressed functionally in murine NIH 3T3 fibroblasts and can be activated by both murine PDGF receptors, alpha and beta type. PMID- 1310470 TI - Involvement of cyclic GMP in the fusion of chick embryonic myoblasts in culture. AB - We found that a transient rise in cGMP levels, which was closely associated with the Ca2+ influx, occurred concomitant with the onset of myoblast fusion. The Ca2+ channel blocker D600 decreased both the cell fusion and the normal rise in cGMP levels. In contrast, the Ca2+ ionophore A23187 transiently increased cGMP levels and induced precocious fusion. In addition, the cGMP analog 8-Br-cGMP induced precocious fusion as A23187 did. The guanylate cyclase inhibitor, methylene blue delayed the fusion in a dose-dependent manner without significantly affecting cell alignment, proliferation, or muscle-specific protein expression. Furthermore, methylene blue delayed the normal rise in cGMP levels, and the fusion block imposed by methylene blue was significantly recovered by 8-Br-cGMP. On the basis of our present findings, we suggest that a Ca2+ influx-dependent rise in cGMP levels is an important step in myoblast fusion. PMID- 1310471 TI - Expression of SPARC is correlated with altered morphologies in transfected F9 embryonal carcinoma cells. AB - SPARC (secreted protein, acidic and rich in cysteine) is a Ca(2+)-binding glycoprotein that has recently been identified as a member of a group of proteins that exert antispreading effects on various cultured cells. In addition, SPARC is induced during the later stages of F9 stem cell differentiation to parietal endoderm (PE). When treated with retinoic acid and dibutyryl cAMP, F9 cells differentiate into PE and SPARC mRNA is increased approximately 20-fold. To determine whether the chronic overexpression or inhibition of expression of SPARC would affect the morphology, attachment, or differentiation of F9 cells, we transfected undifferentiated F9 cells with cDNA encoding SPARC or anti-sense SPARC and cloned lines that expressed either elevated or reduced levels of SPARC protein. The transfected F9 cells displayed altered morphologies in culture: cells of four overexpressing lines appeared clumped and rounded, whereas those of three underexpressing lines were spread and flat, in comparison to controls. Moreover, the morphological differences persisted during differentiation of the lines to PE. The altered morphology was not due to an increased expression of collagenases and did not affect the ability of the cells to attach and adhere to tissue culture plastic. The altered phenotype of the transfected F9 cells appeared to be directly related to the level of extracellular SPARC. Since overexpression of SPARC induced rounding and aggregation of F9 cells in culture, we propose that SPARC facilitates modulation of cell-cell or cell-substrate interactions in vivo. PMID- 1310472 TI - Regulation of adenylate cyclase in electropermeabilized Dictyostelium discoideum cells. AB - In Dictyostelium discoideum cells the enzyme adenylate cyclase is functionally coupled to cell surface receptors for cAMP. Coupling is known to involve one or more G-proteins. Receptor-mediated activation of adenylate cyclase is subject to adaptation. In this study we employ an electropermeabilized cell system to investigate regulation of D. discoideum adenylate cyclase. Conditions for selective permeabilization of the plasma membrane have been described by C.D. Schoen, J. C. Arents, T. Bruin, and R. Van Driel (1989, Exp. Cell Res. 181, 51 62). Only small pores are created in the membrane, allowing exchange of exclusively low molecular weight substances like nucleotides, and preventing the loss of macromolecules. Under these conditions functional protein-protein interactions are likely to remain intact. Adenylate cyclase in permeabilized cells was activated by the cAMP receptor agonist 2'-deoxy cAMP and by the nonhydrolyzable GTP-analogue GTP gamma S, which activates G-proteins. The time course of the adenylate cyclase reaction in permeabilized cells was similar to that of intact cells. Maximal adenylate cyclase activity was observed if cAMP receptor agonist or GTP-analogue was added just before cell permeabilization. If these activators were added after permeabilization adenylate cyclase was stimulated in a suboptimal way. The sensitivity of adenylate cyclase activity for receptor occupation was found to decay more rapidly than that for G-protein activation. Importantly, the adenylate cyclase reaction in permeabilized cells was subject to an adaptation-like process that was characterized by a time course similar to adaptation in vivo. In vitro adaptation was not affected by cAMP receptor agonists or by G-protein activation. Evidently electropermeabilized cells constitute an excellent system for investigating the positive and negative regulation of D. discoideum adenylate cyclase. PMID- 1310473 TI - Differential expression of the fibronectin isoform containing the ED-B oncofetal domain in normal human fibroblast cell lines originating from different tissues. AB - Fibronectin (FN) polymorphism is due both to alternative splicing of three sequences (ED-A, ED-B, and IIICS) of the primary transcript and to post translational modifications. The FN isoform containing the ED-B sequence (B-FN), while having an extremely restricted distribution in normal adult tissues, has a high expression in fetal and tumor tissues. On a panel of non-fetal skin, fetal skin, and fetal lung fibroblast cell lines we have studied, through S1-nuclease protection analysis, the expression of the ED-B containing FN mRNA as well as the expression of the ED-B containing FN isoform through immunoblotting and immunofluorescence techniques, using domain specific monoclonal antibodies. The results show that the expression of B-FN in the different fibroblast cell lines has an extremely great variability depending on the developmental stage of the donor and on the tissue of origin. Moreover, we found that SV-40-transformed fibroblasts present a higher expression of B-FN mRNA with respect to their normal counterparts. An increase in the relative amount of the B-FN isoform in normal human fibroblasts was also obtained by treatment with transforming growth factor beta. PMID- 1310474 TI - Alterations in [3H]kainate and N-methyl-D-aspartate-sensitive L-[3H]-glutamate binding in the rat hippocampal formation following fimbria-fornix lesions. AB - Following lesions of the fimbria-fornix, there is a time-dependent increase in interictal spikes and seizure susceptibility. This may result from sprouting of local excitatory and inhibitory circuits in response to the loss of subcortical and commissural innervation of the hippocampal formation. We used receptor autoradiography to examine the density of N-methyl-D-aspartate (NMDA)-sensitive L [3H]glutamate and [3H]-kainate (KA) binding sites in the hippocampal formation at 5 days, 3 months, and 1 year following bilateral aspiration lesions of the fimbria-fornix. At 5 days post-lesion, the CA3 and CA1 strata radiatum and oriens displayed a decrease (20-42%, P less than 0.01) in NMDA-sensitive L-[3H]glutamate binding. The initial decrease was followed by a moderate recovery at later time points but was still evident at 1 year postlesion. This may reflect a lesion induced turnover of synaptic complexes, down-regulation of postsynaptic receptors, or loss of presynaptic receptors. Five days following fimbria-fornix lesion there was also a decrease (13-15%, P less than 0.05) in [3H]KA binding in CA3 strata radiatum and pyramidale. However, at 3 months postlesion KA receptor density was elevated by 29-33% (P less than 0.01) in the outer molecular layer of the dentate gyrus with no significant change in binding to the inner molecular layer. By 1 year postlesion, the density of [3H]KA binding sites was not significantly different from that observed in control animals of the same age. The increase in KA receptor density in the outer molecular layer 3 months after fimbria-fornix lesion may reflect sprouting of the perforant path input or mossy fibers to this region and contribute to the increase in interictal spikes and seizures susceptibility. PMID- 1310475 TI - Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis. AB - Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBcAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C100-3 and C33c) and structural regions (C22) of HCV. Among the 129 patients, 61 (47%) had antibody to C100-3, 76 (59%) had antibody to C33c and 74 (57%) had antibody to C22. Seventy-nine (61%) were reactive with at least one and 76 (59%) were reactive with at least two HCV peptides (this is the criterion used for hepatitis C virus antibody reactivity). A proportion of patients with chronic hepatitis and cirrhosis (55 of 91; 60%) similar to that of patients without cirrhosis (21 of 38; 55%) had hepatitis C virus antibody. No significant clinical, serum biochemical or histological differences were noted between the group of patients with hepatitis C virus antibody and those without this antibody reactivity. Thus more than half the patients with cryptogenic chronic liver disease had hepatitis C virus antibody, suggesting that chronic HCV infection plays a major role in the origin of cryptogenic chronic hepatitis and cirrhosis. PMID- 1310476 TI - Treatment of hepatocellular carcinoma associated with advanced cirrhosis by transcatheter arterial chemoembolization using autologous blood clot: a preliminary report. AB - Twenty-two patients with hepatocellular carcinoma were treated by a new method of transcatheter arterial chemoembolization using an autologous blood clot as an embolizing agent. All had underlying advanced cirrhosis (14 Child's class B and 8 Child's class C patients). The median follow-up interval was 11 mo (range = 2 to 30 mo). The results of the treatment were compared with those of conventional chemoembolization using gelatin sponge particles for 19 Child's class B patients as historical controls. The survival rate for Child's class B patients treated by the new procedure estimated by the Kaplan-Meier method was 100% at 2 yr, whereas the survival rate for Child's class B patients treated by conventional chemoembolization was 89% at 1 yr and 72% at 2 yr. The survival rate for Child's class C patients was 75% at 1 yr and 50% at 2 yr. Side effects such as pyrexia of more than 38 degrees C or an elevation of the serum bilirubin level of more than 1.5-fold were less common in patients treated by the new method than in those treated by conventional chemoembolization, and thus the new procedure could be performed even for Child's class C patients. The autologous blood clot did not collapse the hepatic arteries even when the embolization was performed repeatedly, and thus fine collateral vessels feeding recurrent hepatocellular carcinoma did not develop. The results suggest that the new chemoembolization using an autologous blood clot is a promising therapeutic procedure in the management of hepatocellular carcinoma associated with advanced cirrhosis. PMID- 1310477 TI - Ito cell expression of a nuclear retinoic acid receptor. AB - Although it has been suggested that retinoids regulate Ito cell proliferation and collagen synthesis, little is known about the ability of Ito cells to respond to retinoids in vivo. Because retinoids may mediate their molecular effects through nuclear receptors, Ito cells were examined for the presence of one of these receptors, nuclear retinoic acid receptor-beta. The modulation of nuclear retinoic acid receptor-beta expression was also studied during cell culture and hepatic fibrogenesis. Northern hybridization analysis revealed that Ito cells freshly isolated from normal rat liver contained nuclear retinoic acid receptor beta messenger RNA at levels significantly higher than those found in other hepatic cell types. Ito cells also contained messenger RNA for two other nuclear retinoic acid receptors, nuclear retinoic acid receptor-alpha and nuclear retinoic acid receptor-gamma. Using an antibody to human nuclear retinoic acid receptor-beta, the nuclear presence of this receptor was demonstrated in normal Ito cells. In contrast, Ito cells cultured for at least 7 days had no detectable messenger RNA or nuclear staining for nuclear retinoic acid receptor-beta despite a 20 +/- 5-fold increase in the messenger RNA level of another retinoid binding protein, cellular retinol binding protein. Analysis of Ito cells isolated from rats with carbon tetrachloride-induced hepatic fibrosis revealed an 81% +/- 3% decrease in nuclear retinoic acid receptor-beta messenger RNA levels in these cells when compared with normal Ito cells. No difference in the messenger RNA levels of cellular retinol binding protein was found in Ito cells isolated from either normal or fibrotic liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310478 TI - New kit on the block: evaluation of second-generation assays for detection of antibody to the hepatitis C virus. PMID- 1310479 TI - Antihypertensive effect of gamma-linolenic acid in spontaneously hypertensive rats. AB - The effects of chronic treatments of adult (aged 16-17 weeks) spontaneously hypertensive rats (SHRs) with different doses of gamma-linolenic acid (GLA) on blood pressure, heart rate, and body weight were studied. Twice-daily injection of SHRs with GLA lowered systolic blood pressure from 175 +/- 4 to 145 +/- 4 mm Hg within 1 week; systolic blood pressure in all three treated groups became stabilized in the normotensive range after 2 weeks of treatment. Control SHRs injected with olive oil showed only a transient decrease in systolic blood pressure on the third day. Heart rate and body weight were not affected by GLA treatment. Withdrawal of GLA treatment resulted in a rapid rise in systolic blood pressure within 1 day from 140 +/- 3 to 165 +/- 3 mm Hg, and it stabilized after 1 week at 191 +/- 5 mm Hg in the three experimental groups. A rapid increase in systolic blood pressure from 175 +/- 5 to 203 +/- 5 mm Hg was also observed in the control group treated with olive oil 1 day after the withdrawal of the treatment. Addition of aspirin (3 mg/kg) with the GLA treatment in olive oil abolished the antihypertensive effect of GLA. In contrast, once-daily treatment with GLA also lowered systolic blood pressure of the SHR, but blood pressure was still in the hypertensive range (170 +/- 6 mm Hg). Systolic blood pressure of control SHRs treated with olive oil was not affected. Plasma from untreated SHRs contained a small amount of GLA. One hour after the injection, the plasma level of GLA increased. We conclude that GLA when given twice daily is an effective antihypertensive agent in the SHR. PMID- 1310480 TI - Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats. AB - The hypothesis that signal transduction mediated by platelet-derived growth factor (PDGF) and angiotensin II (Ang II) is altered in vascular smooth muscle (VSM) cells from the spontaneously hypertensive rat (SHR) was tested by measuring changes in the cytosolic free calcium concentration ([Ca2+]i). [Ca2+]i was measured in cultured aortic smooth muscle cells from SHRs and Wistar-Kyoto (WKY) normotensive rats using fura-2 as a calcium indicator and a microscopic digital image analysis system. Activation of cells with Ang II resulted in a prompt though transient rise in [Ca2+]i; the maximum increase was observed after 10-30 second intervals. On the other hand, activation of cells with PDGF BB produced an increase in [Ca2+]i with a 40-60-second lag period; the maximum increase was observed 2-4 minutes after the addition of PDGF. PDGF-stimulated increases in [Ca2+]i were markedly inhibited by the addition of the calcium channel antagonist verapamil (100 microM) as well as by removal of calcium from the extracellular bathing medium. However, Ang II-stimulated [Ca2+]i was not significantly affected by the addition of verapamil or by removal of extracellular calcium. These results would indicate that PDGF-mediated increases in [Ca2+]i in VSM cells are predominantly via Ca2+ influx, whereas Ang II-mediated increases are due to calcium release from intracellular pools. Basal and PDGF- and Ang II-stimulated increases in [Ca2+]i were significantly greater (p less than 0.05) in SHR VSM cells compared with WKY cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310481 TI - Mechanisms of cardiovascular responses to glycine injected into the dorsal vagal motor nucleus in rat. AB - Microinjection of glycine into the dorsal vagal motor nucleus of anesthetized rats elicits increases in arterial pressure and heart rate. In the nucleus tractus solitarii, where cardiovascular responses to injection of glycine may be mediated through release of acetylcholine, there is a dense concentration of glycinergic nerve terminals and glycine receptors. In this study, using immunohistochemical methods, we show that glycine terminals and receptors are present in caudal dorsal vagal motor nucleus, although the concentration of both terminal elements is less than in adjacent nucleus tractus solitarii. Responses to glycine microinjected into the dorsal vagal motor nucleus are blocked by the muscarinic antagonist atropine microinjected at the same site; but, unlike responses to glycine in the nucleus tractus solitarii, responses to glycine in the dorsal vagal motor nucleus are not prolonged by physostigmine. These data support the possibility that endogenous glycine may play a role as a transmitter in the dorsal vagal motor nucleus. Responses to glycine may be mediated through actions at muscarinic receptors but not through acetylcholine itself. PMID- 1310482 TI - Mild exercise decreases plasma endogenous digitalislike substance in hypertensive individuals. AB - Changes in a plasma endogenous digitalislike substance were investigated in relation to the antihypertensive mechanism of mild exercise. Fifteen women with mild essential hypertension and seven normotensive female volunteers were divided into exercised hypertensive (n = 10), nonexercised hypertensive (n = 5), and nonexercised normotensive (n = 7) groups. A 4-week general clinical observation period preceded the study period of 10 weeks. The exercised hypertensive individuals were treated with a lactate threshold exercise that corresponded to approximately 50% of the maximum oxygen consumption three times a week, whereas the nonexercised groups were observed at the outpatient clinic as control groups. In the exercised group, systolic blood pressure fell by 7 mm Hg (p = 0.05), diastolic by 6 mm Hg (p less than 0.01), and mean blood pressure by 7 mm Hg (p less than 0.01) after 10 weeks. The reduction in the plasma endogenous digitalislike substance was significant after 7 (-1.02 ng/ml, p less than 0.05) and 10 (-1.04 ng/ml, p less than 0.05) weeks in this group. It positively correlated with the reduction in diastolic (r = 0.70, p less than 0.05) or mean (r = 0.66, p less than 0.05) blood pressure and with changes in plasma norepinephrine (r = 0.76, p less than 0.05). The mean corpuscular volume of erythrocytes decreased (-1.7 fl, p less than 0.01) after 10 weeks of exercise, and the plasma volume index tended to decrease (-108 ml/m2, p = 0.28). In the control groups, significant changes in blood pressure and plasma endogenous digitalislike substance were not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310483 TI - Facilitation of noradrenergic transmission by angiotensin in hypertensive rats. AB - We examined the angiotensin-induced potentiation of noradrenergic transmission in the isolated mesenteric arteries of one-kidney, one clip (1K1C) hypertensive rats. The angiotensin converting enzyme activity measured in plasma did not change during the development of hypertension, whereas the activity measured in the aortic tissue was significantly augmented 28 days after the renal artery was clipped. Although the pressor responses to nerve stimulation were basically unaltered, a significant increase in the sensitivity to norepinephrine developed during hypertension. The 1K1C preparations presented an increased sensitivity to the facilitatory effect of angiotensin II on the response to periarterial nerve stimulation. The facilitatory effect of angiotensin II on both nerve stimulation and exogenous norepinephrine was blocked by saralasin. Angiotensin I induced similar facilitatory action on noradrenergic transmission that was inhibited by saralasin. When a high concentration of angiotensin I was used, the facilitatory effect was significantly higher in mesenteric arteries from 1K1C rats than in controls. Captopril reduced the facilitatory effect of angiotensin I in 1K1C preparations, whereas the responses of the normotensive control rats were unaffected by captopril. These findings are consistent with angiotensin I acting directly on angiotensin II receptors or with angiotensin I being converted to angiotensin II by an alternative pathway not involving angiotensin converting enzyme. PMID- 1310484 TI - Production of angiotensin-(1-7) by human vascular endothelium. AB - The heptapeptide angiotensin-(1-7) is a circulating biologically active product of the renin-angiotensin system. In this study, we evaluated the role of the vascular endothelium in the formation of angiotensin-(1-7). Metabolism of 125I angiotensin I was investigated using confluent cultured bovine and human aortic and umbilical vein endothelial cells. The fetal calf serum-supplemented medium was replaced by serum-free medium containing 0.2% bovine serum albumin. One hour later, this medium was replaced by serum-free medium containing 125I-angiotensin I. After incubation of 125I-angiotensin I for various intervals at 37 degrees C, the medium was collected and analyzed for formed products by high-performance liquid chromatography. Products of angiotensin I metabolism were identified by comparison of their retention times with those of radiolabeled standards. The contribution of proteases released into the medium was evaluated by incubation of 125I-angiotensin I with medium previously incubated for 1 hour with endothelial cells. Incubation of 125I-angiotensin I with bovine and human endothelial cells produced a time-dependent generation of 125I-angiotensin-(1-7) greater than 125I angiotensin II greater than 125I-angiotensin-(1-4). Generation of angiotensin peptides was not due to the presence of proteases in the medium. When human umbilical endothelial cells were incubated in the presence of the angiotensin converting enzyme inhibitor enalaprilat (1 microM), generation of angiotensin II was undetectable. In contrast, angiotensin-(1-7) production increased by an average of 30%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310485 TI - Effect of protein kinase C and calcium on bradykinin-mediated contractions of rabbit vessels. AB - Bradykinin caused graded contractions of rings of rabbit aorta and jugular vein with EC50 values of 1.3 microM and 2.2 nM. In denuded preparations, responses of bradykinin in jugular vein but not in aorta were potentiated 1,000-fold. Both preparations bathed in calcium-free solution showed markedly depressed responses to bradykinin, but addition of 1 mM EGTA further inhibited bradykinin responses only in aorta. Time-course experiments carried out in calcium-free solution plus EGTA revealed that bradykinin contractions in rabbit aorta were very sensitive to extracellular calcium, whereas responses of the jugular vein depended on both extracellular and intracellular calcium sources. Responses to bradykinin in both tissues were unaffected by nicardipine (1 microM) but were partially antagonized by NiCl2 (0.1-0.3 mM). Ryanodine (30 microM) incubated in calcium-free medium markedly inhibited jugular vein responses to bradykinin but had no effect on aortic responses. Phorbol ester (1 microM) caused a slow tonic contraction in jugular vein but not in aorta and inhibited bradykinin responses in the former preparation. Staurosporine (1-100 nM) and 1-(5-isoquinolinesulfonyl)-2 methylpiperizine (H-7, 3 and 10 microM) caused a dose-dependent inhibition of bradykinin-induced contractions in jugular vein but were less effective in aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310486 TI - Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats. AB - The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2 +/- 0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA salt rats (106 +/- 22 fmol/mg protein) than in uninephrectomized rats (172 +/- 19 fmol/mg protein, p less than 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with [3H]myoinositol. Inositol phosphates were separated by high performance liquid chromatography. In response to 100 nmol/l ET-1, accumulation of inositol 1,4,5-trisphosphate after 20 seconds and of inositol monophosphate, inositol bisphosphate, and inositol 1,3,4-triphosphate after 30 minutes (in the presence of 25 mmol/l LiCl) were significantly lower in DOCA-salt hypertensive than in uninephrectomized control rats, in both aorta and mesenteric arteries. In conclusion, decreased density of ET-1 receptors in DOCA-salt hypertensive rats results in decreased activation of phospholipase C and, consequently, reduced vasoconstriction induced by ET-1. Because the decrease in vasoconstrictor effects of ET-1 is found in the absence of endothelium, it is likely that receptor downregulation rather than prior receptor occupancy underlies these findings. PMID- 1310487 TI - Detection of antibodies to a linear epitope on the major coat protein (L1) of human papillomavirus type-16 (HPV-16) in sera from patients with cervical intraepithelial neoplasia and children. AB - Antibodies to the major (L1) coat protein of human papillomavirus type 16 (HPV 16) in sera from patients with cervical intra-epithelial neoplasia (CIN) have been investigated by means of recombinant proteins and synthetic peptides. When L1-HPV-16 fusion proteins were used in immunoblot assays, no antibody reactivity was found in sera from 52 patients with CIN or from 21 unrelated children. Amino acid sequence analyses indicated that L1-HPV-16 amino acids 473 to 492 may contain an HPV-16 type-restricted epitope since the greatest diversity occurs in this region. In the ELISA, seropositivity to peptides 473 to 492 was more common among CIN patients whose biopsies contained HPV-16 DNA (91%, 21 of 23) than among their children (24%, 5 of 21; p less than 0.001) or other CIN patients with HPV 16 DNA-negative biopsies (66%, 19 of 29; p less than 0.05), but was unrelated to the severity of the CIN lesion. Antibodies to L1-HPV-16 peptide 473 to 492 among seropositive CIN patients cross-reacted with the analogous L1-HPV-33, but not with the L1-HPV-6b peptide, and were predominantly IgM. In contrast, antibodies which recognized a less variable region of L1-HPV-16 (amino acids 279 to 293) showed no association with HPV-16 DNA status. Seropositivity to the L1-HPV-6b (amino acids 473-492) was less frequent (33%) among CIN patients and unassociated with HPV-16 DNA status (p greater than 0.1); however 51% (37 of 72) of patients with genital warts had antibodies to this peptide. PMID- 1310488 TI - Expression and splicing patterns of human papillomavirus type-16 mRNAs in pre cancerous lesions and carcinomas of the cervix, in human keratinocytes immortalized by HPV 16, and in cell lines established from cervical cancers. AB - We have analysed the splicing patterns of human papillomavirus (HPV) type-16 mRNAs in a human epithelial cell line immortalized by HPV 16 (HPKII), in cell lines established from cervical carcinomas (SiHa and CaSki) and in pre-invasive and invasive carcinomas of the cervix. The presence of mRNA species previously described, which could encode the E6, E6I, E6II, E6III, E7, E2, E2C, E4, E5 and L1 proteins, was determined, using the RNA polymerase chain reaction (PCR) technique with primers that flank unique splice sites. The state of the viral DNA in the tumor biopsies was established by Southern blot analysis. The various HPV 16 transcripts could be detected in cell lines and in tumor biopsies. The size of the RNA PCR products were in agreement with the previously mapped splice sites. The full range of transcripts was revealed in the HPKII cell line and in a number of pre-invasive carcinomas. Messenger RNAs which could encode the E6III, E4 and E5 proteins were most prevalent in all types of tumor. The overall results of DNA and RNA analyses in cell lines and tumor specimens indicate that (1) expression of either of the early or late transcripts studied is not specifically related to (a) tumor stage or (b) the physical state of the viral genome; and (2) alterations in the splicing patterns of HPV 16 transcripts may not be involved in tumor progression. PMID- 1310489 TI - Different fatty-acid profiles in phosphoinositides from human fibroblastic meningiomas with or without chromosome 22 monosomy. AB - The fatty-acid composition of phosphoinositides derived from 13 human fibroblastic meningiomas, divided according to the presence or the absence of monosomy of chromosome 22, was analyzed. Phosphoinositides were separated into their 3 main components: phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate. In all the tumors, regardless of cytogenetic differences, remarkable differences were detected between phosphatidylinositol and phosphatidylinositol-4-phosphate or phosphatidylinositol 4,5-bisphosphate. In meningiomas with 22 monosomy, there was a significant decrease in the relative amount of arachidonate in all the phosphoinositide fractions; this situation might determine diminished down-regulation of the corresponding diacylglycerol, derived by the phospholipase-C-stimulated hydrolysis of phosphoinositides, and, consequently, different protein-kinase-C stimulation. PMID- 1310490 TI - Increased phosphorylation of nuclear phosphoproteins in human lung-cancer cells resistant to cis-diamminedichloroplatinum (II). AB - A novel non-phorbol-ester-like tumor promoter, okadaic acid (OA) has been shown to be an inhibitor of protein phosphatase I and IIA and, thus, to cause an "apparent activation" of protein kinase C (PKC). We previously showed that cis diamminedichloroplatinum(II) (CDDP)-resistant cells, PC-9/CDDP, were cross resistant to OA and that the cross-resistance was not due to the increased efflux of OA. We hypothesized that the phosphorylation status of some cellular proteins might be important in CDDP-resistance. No significant difference in PKC activity or total protein phosphatase activity measured in vitro was seen between PC-9 and PC-9/CDDP cells, nor in their sensitivity to inhibition by OA, nor in the amount of phosphorylation of whole cells or TCA-insoluble material. By SDS-PAGE after incubation of intact cells with 32P, we detected a marked increase, compared to PC-9 cells, in phosphorylation of the nuclear proteins of MW 32 and 20 kDa in CDDP-resistant PC-9/CDDP cells with no apparent difference in protein content. When phosphorylation of nuclear proteins observed in PC-9/CDDP cells was analyzed by 2-dimensional SDS-PAGE, the 32-kDa protein had a PI of about 4.5. The 32-kDa and 20-kDa bands were increased in a dose-dependent manner by CDDP treatment. On the other hand, no increase in phosphorylation of these proteins was observed in parental PC-9 cells. These results demonstrate a marked difference in the phosphorylation status of specific nuclear proteins between parental and CDDP resistant cell lines, which may be related to CDDP-resistance. PMID- 1310491 TI - Enhanced insulin-receptor tyrosine kinase activity associated with chromosomal translocation (1;19) in a pre-B-cell leukemia line. AB - The gene for the insulin receptor has been assigned to chromosome 19 near the breakpoint of the translocation t(1;19) which occurs in 25% of pre-B-cell leukemias. Insulin receptors in a pre-B-cell leukemia cell line (ACV) with t(1;19) were found to have 2-fold higher affinity for insulin, 5-fold higher basal and insulin-stimulated beta sub-unit autophosphorylation, and 2-fold higher basal and 4-fold higher insulin-stimulated beta sub-unit kinase activity on the synthetic peptide poly(Glu,Tyr), compared to receptors in a B-cell line (ADD) with normal karyotype from the same patient. ACV cells had a novel 13-kb receptor mRNA species and expressed a DNA polymorphism localized to the tyrosine kinase domain of the receptor gene. These findings suggest that t(1;19) in the ACV cell may result in rearrangement of the insulin receptor gene and translation of a receptor with enhanced tyrosine kinase activity. PMID- 1310492 TI - The case against mandatory HIV testing of health care workers. PMID- 1310493 TI - Varicella zoster and herpes simplex virus infections. AB - There are six herpes viruses, three of which, the varicella-zoster virus and the herpes simplex viruses types 1 and 2, are of particular concern to patients and staff in critical care units. These viruses, especially in their reactivated states, may present atypically in critically ill and immune-suppressed patients, and, by the time the diagnosis is made, exposures of other patients and clinicians may have occurred. Pregnancy and immunosuppressed states can result in severe, even life-threatening varicella-zoster virus infections in susceptible adults. Similarly, nosocomial herpes simplex virus infections can have serious consequences for exposed patients and staff. An additional problem after herpes simplex virus infection is the potential of lifelong and possibly frequent recurrences. In this article, the manifestations, modes of transmission, and treatment will be discussed. Special emphasis will be placed on describing the types of patients who are at high risk of presenting with varicella-zoster virus or herpes simplex virus infection so that physicians and nurses can use appropriate preventive measures to avert nosocomial infections in patients and staff. PMID- 1310494 TI - Development of an ELISA for the detection of 2-nitroimidazole hypoxia markers bound to tumor tissue. AB - Canine and rodent tumors covalently bind the fluorinated 2-nitroimidazole, CCI 103F, in a way that immunohistochemical analysis shows is consistent with the location of tumor hypoxia. We have now developed a rapid, quantitative, and non radioactive enzyme linked immunosorbent assay for the binding of CCI-103F in biopsy samples of spontaneous canine tumors. Issues of antigen stability during tissue processing, calibration of the ELISA, and the use of biopsy samples for measuring tumor hypoxia by the ELISA approach are addressed. PMID- 1310495 TI - Potentiation of radiation response in human carcinoma cells in vitro and murine fibrosarcoma in vivo by topotecan, an inhibitor of DNA topoisomerase I. AB - DNA topoisomerase I, a nuclear enzyme important for solving topologic problems arising during DNA replication, has been identified as a principal target of a plant alkaloid, 20(s)-camptothecin. In view of the profound biochemical effects of camptothecin and its analogues on DNA replication and the differential cytotoxic effects on human tumors in xenografts, experiments were performed to determine whether topotecan, a camptothecin analogue, would potentiate the radiation effects on human carcinoma cells in culture and murine fibrosarcoma in mice. Cell culture studies showed that a dose dependent reduction in cell survival was obtained with a 4 hr exposure of the drug following irradiation of cells. No enhancement of cell killing was seen when cells were treated with the drug before irradiation. Preliminary in vivo tumor studies showed a significant radiosensitizing effect of topotecan that was both drug dose (20 mg/kg) and time sequence (4 hr before irradiation) dependent. There was no enhanced skin reaction following the combined treatments. PMID- 1310496 TI - Interaction of buthionine sulfoximine and the stabilization of DNA-topoisomerase II complexes by doxorubicin. AB - Although it has been shown previously that the depletion of cellular thiols increases doxorubicin cytotoxicity, the mechanism of sensitization is not clear. To study this question, the effect of D,L-buthionine-S,R-sulfoximine (BSO) on doxorubicin cytotoxicity and the stabilization of DNA-topoisomerase II complexes (cleavable complexes) was investigated in V79 cells. Incubations with BSO (10 mM) were for 5 hr beginning 4 hr prior to doxorubicin exposure since a 4 hr incubation with 10 mM BSO is known to decrease glutathione levels below 5% of control V79 cells. These BSO pre-treatment increased doxorubicin cytotoxicity. At doxorubicin concentrations of 5 micrograms/ml, BSO resulted in an 8-10 fold decrease in surviving cells, compared to cells exposed to doxorubicin alone. It was determined that BSO pre-treatments did not affect the accumulation of doxorubicin into the cell, the rate of cleavable complex stabilization by doxorubicin, or the rate of dissociation of stabilized cleavable complexes. These data suggest that BSO-induced doxorubicin sensitization occurs at a step following the stabilization of cleavable complexes or by an independent mechanism. PMID- 1310497 TI - The efficacy of pharmacokinetic monitoring and dose modification of etanidazole on the incidence of neurotoxicity: results from a phase II trial of etanidazole and radiation therapy in locally advanced prostate cancer. AB - Fifty-four patients have been entered on a Phase II trial to study the efficacy of etanidazole (ETA) for locally advanced prostate cancer. The primary goal was to study the incidence of and time to a complete response for patients receiving ETA and radiation therapy. The secondary goal was to prospectively evaluate the utility of pharmacokinetic monitoring and dose-modification of the incidence and severity of the dose-limiting peripheral neurotoxicity. Within a constant radiation therapy regimen, the dose of ETA was either (a) unmodified (2 g/m2, 3 times weekly for 17 doses); (b) altered by a schedule modification of either number of doses or dose adjustment; or (c) individualization of single dose size so that the total number of doses (19 doses) were maintained but the single dose size was adjusted to keep the total AUC of plasma concentration versus time to less than 40 mM-hr. Sufficient efficacy data are not yet available. The use of drug dose modification has reduced the incidence of neurotoxicity from (a) unmodified: 17/26 = 65% (1 grade II); (b) schedule adjustment: 5/9 = 55% (no grade II); and (c) individualized dose modification: 1/19 (no grade II) = 6%. The minimum number of time points needed to accurately assess the AUC will be determined. Pharmacokinetic monitoring will be important in the use of ETA so that drug underdosing can be avoided while minimizing the risk of serious neurotoxicity. PMID- 1310498 TI - Inhibition of the recBCD-dependent activation of Chi recombinational hot spots in SOS-induced cells of Escherichia coli. AB - Nucleotide sequences called Chi (5'-GCTGGTGG-3') enhance homologous recombination near their location by the RecBCD enzyme in Escherichia coli (Chi activation). A partial inhibition of Chi activation measured in lambda red gam mutant crosses was observed after treatment of wild-type cells with DNA-damaging agents including UV, mitomycin, and nalidixic acid. Inhibition of Chi activation was not accompanied by an overall decrease of recombination. A lexA3 mutation which blocks induction of the SOS system prevented the inhibition of Chi activation, indicating that an SOS function could be responsible for the inhibition. Overproduction of the RecD subunit of the RecBCD enzyme from a multicopy plasmid carrying the recD gene prevented the induced inhibition of Chi activation, whereas overproduction of RecB or RecC subunits did not. It is proposed that in SOS-induced cells the RecBCD enzyme is modified into a Chi-independent recombination enzyme, with the RecD subunit being the regulatory switch key. PMID- 1310499 TI - Characterization of two hypertransposing Tn5 mutants. AB - Transposition of Tn5 in Escherichia coli is regulated by two transposon-encoded proteins: transposase (Tnp), promoting transposition preferentially in cis, and the trans-acting inhibitor (Inh). Two separate transposase mutants were isolated that replace glutamate with lysine at position 110 (EK110) and at position 345 (EK345). The EK transposase proteins increase the Tn5 transposition frequency 6- to 16-fold in cis and enhance the ability of transposase to act in trans. The purified mutant transposase proteins interact with transposon outside end DNA differently from the wild-type protein, resulting in the formation of a novel complex in gel retardation assays. During characterization of the transposase proteins in the absence of inhibitor, we found that wild-type transposase itself has a transposition-inhibiting function and that this inhibition is reduced for the mutant proteins. We present a model for the regulation of Tn5 transposition, which proposes the existence of two transposase species, one cis-activating and the other trans-inhibiting. The phenotype of the EK transposase mutants can be explained by a shift in the ratio of these two species. PMID- 1310500 TI - Isolation and characterization of the Escherichia coli htrD gene, whose product is required for growth at high temperatures. AB - Those genes in Escherichia coli defined by mutations which result in an inability to grow at high temperatures are designated htr, indicating a high temperature requirement. A new htr mutant of E. coli was isolated and characterized and is designated htrD. The htrD gene has been mapped to 19.3 min on the E. coli chromosome. Insertional inactivation of htrD with a mini-Tn10 element resulted in a pleiotropic phenotype characterized by a severe inhibition of growth at 42 degrees C and decreased survival at 50 degrees C in rich media. Furthermore, htrD cells were sensitive to H2O2. Growth rate analysis revealed that htrD cells grow very slowly in minimal media supplemented with amino acids. This inhibitory effect has been traced to the presence of cysteine in the growth medium. Further studies indicated that the rate of cysteine transport is higher in htrD cells relative to the wild type. All of these results, taken together, indicate that the htrD gene product may be required for proper regulation of intracellular cysteine levels and that an increased rate of cysteine transport greatly affects the growth characteristics of E. coli. PMID- 1310501 TI - Characterization of In0 of Pseudomonas aeruginosa plasmid pVS1, an ancestor of integrons of multiresistance plasmids and transposons of gram-negative bacteria. AB - Many multiresistance plasmids and transposons of gram-negative bacteria carry related DNA elements that appear to have evolved from a common ancestor by site specific integration of discrete cassettes containing antibiotic resistance genes or sequences of unknown function. The site of integration is flanked by conserved segments coding for an integraselike protein and for sulfonamide resistance, respectively. These segments, together with the antibiotic resistance genes between them, have been termed integrons (H. W. Stokes and R. M. Hall, Mol. Microbiol. 3:1669-1683, 1989). We report here the characterization of an integron, In0, from Pseudomonas aeruginosa plasmid pVS1, which has an unoccupied integration site and hence may be an ancestor of more complex integrons. Codon usage of the integrase (int) and sulfonamide resistance (sul1) genes carried by this integron suggests a common origin. This contrasts with the codon usage of other antibiotic resistance genes that were presumably integrated later as cassettes during the evolution and spread of these DNA elements. We propose evolutionary schemes for (i) the genesis of the integrons by the site-specific integration of antibiotic resistance genes and (ii) the evolution of the integrons of multiresistance plasmids and transposons, in relation to the evolution of transposons related to Tn21. PMID- 1310502 TI - Characterization of the novel nisin-sucrose conjugative transposon Tn5276 and its insertion in Lactococcus lactis. AB - A novel, chromosomally located conjugative transposon in Lactococcus lactis, Tn5276, was identified and characterized. It encodes the production of and immunity to nisin, a lanthionine-containing peptide with antimicrobial activity, and the capacity to utilize sucrose via a phosphotransferase system. Conjugal transfer of Tn5276 was demonstrated from L. lactis NIZO R5 to different L. lactis strains and a recombination-deficient mutant. The integration of Tn5276 into the plasmid-free strain MG1614 was analyzed by using probes based on the gene for the nisin precursor (nisA) and the gene for sucrose-6-phosphate hydrolase (sacA). The transposon inserted at various locations in the MG1614 chromosome and showed a preference for orientation-specific insertion into a single target site (designated site 1). By using restriction mapping in combination with field inversion gel electrophoresis and DNA cloning of various parts of the element including its left and right ends, a physical map of the 70-kb Tn5276 was constructed, and the nisA and sacA genes were located. The nucleotide sequences of Tn5276 junctions in donor strain NIZO R5 and in site 1 of an MG1614-derived transconjugant were determined and compared with that of site 1 in recipient strain MG1614. The results show that the A + T-rich ends of Tn5276 are flanked by a direct hexanucleotide repeat in both the donor and the transconjugant but that the element does not contain a clear inverted repeat. PMID- 1310503 TI - DNA sequence of IS91 and identification of the transposase gene. AB - IS91 is a 1,830-bp insertion sequence that inserts specifically at the sequence CAAG or GAAC of the target and does not duplicate any sequence upon insertion (23). By transposon mutagenesis, we have identified open reading frame 426 (ORF426; bp 454 to 1731) as the putative ORF for the transposase. It displays a cysteine-rich, potential metal-binding domain in its N-terminal region. Adjacent to ORF426, there is an ORF (ORF121) which precedes and terminally overlaps ORF426 by one amino acid. Tn1732 insertions in ORF121 do not affect the transposition frequency. IS91 has sequence similarities to IS801 from Pseudomonas syringae. Their putative transposases are 36% identical, including conservation of the cysteine-rich cluster. The information concerning IS801 insertion specificity and target duplication has been reevaluated in the light of our results. PMID- 1310504 TI - Isocitrate dehydrogenase kinase/phosphatase: identification of mutations which selectively inhibit phosphatase activity. AB - Mutations in aceK, the gene encoding isocitrate dehydrogenase kinase/phosphatase, which selectively inhibit phosphatase activity have been isolated. These mutations yield amino acid substitutions within a 113-residue region of this 578 residue protein. These mutations may define a regulatory domain of this protein. PMID- 1310505 TI - A 24-amino-acid polypeptide is essential for the biosynthesis of the coenzyme pyrrolo-quinoline-quinone. AB - At least four genes are required for the biosynthesis of the coenzyme pyrrolo quinoline-quinone (PQQ) in Acinetobacter calcoaceticus. The DNA region where one of these genes was mapped codes for a polypeptide of only 24 amino acids. Here we show that indeed this small peptide is essential for PQQ synthesis. Site-directed mutagenesis shows that at least one glutamate and one tyrosine residue of the polypeptide are essential for its function. PMID- 1310506 TI - Effect of a novel class I antiarrhythmic agent, TYB-3823, on the calcium current in single guinea pig ventricular myocytes. AB - The effect of TYB-3823 on Ca2+ current (ICa) of guinea pig ventricular myocytes was investigated by means of whole-cell patch-clamp technique. TYB-3823 (100 1,000 microM) caused a concentration-dependent decrease in ICa. Furthermore, a reduction of ICa induced by TYB-3823 (1,000 microM) was progressively accentuated by repetitive membrane depolarization, indicating a rate-dependent block of ICa. However, the inhibitory potency on ICa was approximately 1/1000 of a Ca2+ antagonistic agent, verapamil hydrochloride. Considering evidence that 3-30 microM TYB-3823 decreased the maximum upstroke velocity of the action potential of guinea pig ventricular muscles, it is indicated that the drug does not show its Ca2+ antagonistic property in the usual concentration range as a class I antiarrhythmic agent. PMID- 1310507 TI - Serologic evidence of active Epstein-Barr virus infection in Epstein-Barr virus associated lymphoproliferative disorders of children with acquired immunodeficiency syndrome. AB - The DNA and nuclear antigens of Epstein-Barr virus (EBV) have been detected in specimens of tissue of non-Hodgkin lymphoma and lymphocytic interstitial pneumonitis from patients with acquired immunodeficiency syndrome. To determine whether there is serologic evidence of an active EBV infection in these disorders, we conducted a case-control study. The case patients were 10 children with acquired immunodeficiency syndrome and EBV genome-positive pneumonitis or lymphoma. We randomly selected one or, if available, two matched control patients with human immunodeficiency virus infection for each index patient and compared their EBV serologic profiles with those of the index case patient at the time of the biopsy. Ten case patients and 13 matched control patients were enrolled. All 10 case patients (100%) compared with 2 (15%) of 13 matched control patients had serologic evidence of either a primary or a reactivated EBV infection at the time the index patient had a biopsy performed (p less than 0.001). Therefore we found serologic and virologic evidence that EBV is etiologically related to EBV associated lymphocytic interstitial pneumonitis and non-Hodgkin lymphoma in children with acquired immunodeficiency syndrome. PMID- 1310508 TI - Oral itraconazole therapy for disseminated candidiasis in low birth weight infants. PMID- 1310509 TI - Determinants of response to the DNA topoisomerase II inhibitors doxorubicin and etoposide in human lung cancer cell lines. AB - BACKGROUND: Small-cell lung cancer (SCLC) is more sensitive to anticancer agents than non-small-cell lung cancer (NSCLC), but few studies have analyzed the mechanisms of natural drug resistance responsible for this difference. PURPOSE: To elucidate these mechanisms, we determined drug sensitivity and evaluated the biochemical parameters affecting response to the DNA topoisomerase II inhibitors doxorubicin and etoposide in both types of cancer cell lines, in particular the activity and content of DNA topoisomerase II, as well as etoposide uptake and cell doubling time. METHODS: Drug sensitivity and cellular uptake of etoposide were determined by clonogenic assay and accumulation of radiolabeled drug, respectively. The topoisomerase II activity was assayed by decatenation of kinetoplast DNA to minicircle DNA using nuclear protein, and the content was determined by immunoblot analysis of nuclear extracts. We also compared the topoisomerase II content in parent cell lines with that in lines with cisplatin resistance acquired in vitro. RESULTS: Sensitivities to doxorubicin and etoposide were higher in SCLC cell lines than in NSCLC lines, and the difference was statistically significant. Etoposide uptake in SCLC cells was higher than in NSCLC cells; the difference was statistically significant, but this difference may not be sufficient to account for the variation in sensitivities of the cell lines. Topoisomerase II activities of nuclear protein from SCLC cell lines were reproducibly twofold higher than those for NSCLC cell lines. The topoisomerase II content in nuclear protein appeared to be higher in SCLC cell lines than in NSCLC cell lines and corresponded to the sensitivities to doxorubicin and etoposide. In the cisplatin-resistant NSCLC cell lines PC-7/CDDP and PC-14/CDDP, the topoisomerase II content was increased compared with that in the parent lines, but the topoisomerase II content in other cisplatin-sensitive parent lines was similar to that in resistant sublines. CONCLUSIONS: These findings suggest that the topoisomerase II activity and content may be major factors in determining sensitivity to topoisomerase II inhibitors. PMID- 1310510 TI - Fewer colon polyps found in men with high-fiber, low-fat diets. PMID- 1310511 TI - Relationship of diet to risk of colorectal adenoma in men. AB - BACKGROUND: Rates of colorectal cancer in various countries are strongly correlated with per-capita consumption of red meat and animal fat and inversely associated with fiber consumption. There have been few studies, however, of dietary risk factors for colorectal adenomas, which are precursors of cancer. PURPOSE: Our purpose was to determine prospectively the relationship between dietary factors and risk of colorectal adenomas. METHODS: Using data from the Health Professionals Follow-up Study, we documented 170 cases of adenomas of the left colon or rectum in 7284 male health professionals who completed a food frequency questionnaire in 1986 and who had a colonoscopy or sigmoidoscopy between 1986 and 1988. Relative risk (RR) of adenoma was determined according to quintiles of nutrient intakes. RESULTS: After adjustment for total energy intake, saturated fat was positively associated with risk of colorectal adenoma (P for trend = .006); RR for the highest versus the lowest quintile of intake was 2.0 (95% confidence interval [CI] = 1.2-3.2). Dietary fiber was inversely associated with risk of adenoma (P for trend less than .0001); RR for men in the highest versus the lowest quintile was 0.36 (95% CI = 0.22-0.60). All sources of fiber (vegetables, fruits, and grains) were associated with decreased risk of adenoma. For subjects on a high-saturated fat, low-fiber diet, the RR was 3.7 (95% CI = 1.5-8.8) compared with those on a low-saturated fat, high-fiber diet. The ratio of the intake of red meat to the intake of chicken and fish was positively associated with risk of adenoma (P for trend = .02). CONCLUSIONS: These prospective data provide evidence for the hypothesis that a diet high in saturated fat and low in fiber increases the risk of colorectal adenoma. They also support existing recommendations to substitute chicken and fish for red meat in the diet and to increase intake of vegetables, fruits, and grains to reduce risk of colorectal cancer. PMID- 1310512 TI - Health care workers infected with the human immunodeficiency virus. The next steps. AB - The tragedy of five patients who contracted human immunodeficiency virus (HIV) infection from a seropositive dentist has alarmed the public. The Centers for Disease Control (CDC) recently revised its recommendations for preventing the transmission of HIV infection to patients during invasive procedures. The CDC abandoned a previous plan to list exposure-prone invasive procedures that HIV infected health care workers should not perform. The CDC said "expert review panels" should decide on a case-by-case basis whether seropositive health care workers may perform invasive procedures. As of February 1992, the revised recommendations were under review by the US Department of Health and Human Services. Many issues remain to be clarified, such as how these panels will operate and whether decisions will be consistent in similar cases. Disregarding the CDC guidelines or infection-control precautions may further erode public trust and lead to draconian restrictions on HIV-infected health care workers. Physicians and dentists should respond more effectively to public fears about HIV transmission. The challenge is to protect patients while respecting the privacy and livelihood of health care workers. PMID- 1310513 TI - Dynamic model of differentiation in Ewing's sarcoma cells. Comparative analysis of morphologic, immunocytochemical, and oncogene expression parameters. AB - We report the establishment of a model of neural differentiation in four well characterized Ewing's sarcoma cell lines. This process was induced by serum depleted medium (1% fetal bovine serum) and agents such as dibutyryl cyclic AMP and retinoic acid. The morphologic changes were characterized predominantly by the presence of neurite-like elongated processes showing varicosities and branching along their course with numerous internal filaments and electron-dense granules. Immunocytochemically, differentiation was accompanied by a considerable increase in reactivity for neural markers of several types: neuroblastic, neuroepithelial, neuroendocrine, Schwannian and even glial. In contrast, the tumor promoter, phorbol 12-myristate 13-acetate inhibited differentiation. Several morphologic changes were observed in phorbol 12-myristate 13-acetate treated cells: the cells became smaller and rounder, were poorly adherent to substrate, by electron microscopy lacked cytoplasmic organelles, electron-dense granules or neural processes, and showed decreased expression of neural markers. Northern blot analysis was performed to establish whether there was any relationship between neural differentiation and degree of N-myc, c-myc and dbl oncogene expression. There was no N-myc oncogene expression in the mRNA of Ewing's sarcoma cells, even after neural induced differentiation. The degree of c myc and dbl oncogene expression appeared heterogeneous, and varied with the culture condition. Based on these results, it may be inferred that Ewing's sarcoma cells in vitro display a variable neural phenotype, there being a variety of biologic responses to diverse culture media and various differentiation agents, but with no consistent effect on N-myc, c-myc and dbl oncogene expression. PMID- 1310514 TI - Ploidy of testicular carcinoma in situ. AB - The ploidy of carcinoma in situ and invasive germ cell tumors of the adult testis was compared by DNA flow cytometry. Irrespective of the tumor type with which it was associated, the median DNA index of carcinoma in situ was about the same as that of seminomas and higher than the DNA index of invasive nonseminomatous germ cell tumors. These data indicate that seminoma and carcinoma in situ cells are not only phenotypically similar but also have the same ploidy. PMID- 1310515 TI - Comparative effects of tetrandrine and berbamine on production of the inflammatory cytokines interleukin-1 and tumor necrosis factor. AB - Tetrandrine and berbamine are bisbenzylisoquinoline compounds which differ from each other in a minor way in terms of chemical structure, yet tetrandrine is 6-18 times more potent than berbamine in terms of inhibitory effects on production of interleukin-1 and tumor necrosis factor (TNF alpha) by monocytes and macrophages, and TNF beta production by lymphocytes. Moreover, tetrandrine significantly suppressed phosphoinositide turnover while berbamine did not. These findings may provide important insights into structure-activity relationships and the design of novel analogues and congeners useful in the therapy of chronic inflammatory and auto-immune diseases. PMID- 1310516 TI - Long-term therapy with high-dose simvastatin does not affect adrenocortical and gonadal hormones in hypercholesterolemic patients. AB - Simvastatin is an effective hypocholesterolemic drug that inhibits cholesterol synthesis selectively in the liver, but could have potential side effects on the adrenal gland, ovary, and testis, as these three glands use cholesterol for their hormonal biosynthesis. In this report, we examined adrenal and sex steroids in 10 type IIA hypercholesterolemic patients (three with familial [FH] and seven with polygenic hypercholesterolemia) over a period of 1 year on simvastatin therapy in order to confirm in vivo its selective action. Furthermore, we evaluated the adrenal reserve by a corticotropin rapid test, before starting treatment and again at the end of the third month on 20 mg of simvastatin per day, then at the sixth and 12th month on 40 mg/d. There was a significant lowering of total cholesterol (TC) (-31%), low-density lipoprotein cholesterol (LDL-C) (-39%), and apolipoprotein (apo) B (-39%); no statistically significant differences were seen in cortisol response to the corticotropin test between baseline and simvastatin treated patients. No variation of any sex steroid was observed in patients of either gender. We conclude that long-term therapy with high-dose simvastatin does not interfere with either adrenocortical function or sex hormone production. PMID- 1310517 TI - Erythrocyte sodium-potassium ATPase activity and thiol metabolism in genetically hyperglycemic mice. AB - Erythrocyte sodium pump activity, osmotic fragility, and thiol status were measured in genetically hyperglycemic (db/db) mice and compared with their nondiabetic littermates (db/m). The data showed no major differences in these parameters. However, erythrocytes from streptozotocin (Stz)-induced diabetic rats had significantly lower activity of sodium pump and thiols with an almost fourfold increase in osmotic fragility as compared with erythrocytes from nondiabetic rats. Sorbinil (an aldose reductase inhibitor) treatment of Stz diabetic rats normalized all these lesions, suggesting a key role for polyol pathway. However, sorbitol levels in erythrocytes from db/db and db/m mice were undetectable. The data suggest that in db/db mice, the relative lack of polyol pathway, a potential consumer of NADPH, may provide erythrocytes with optimal NADPH for glutathione reductase system, thus maintaining normal GSH levels even at the height of hyperglycemia. Thus, the genetically hyperglycemic mice may serve as a useful model to study diabetes related complications without involving polyol pathway. PMID- 1310518 TI - Drugs for treatment of fungal infections. PMID- 1310519 TI - Gene targeting in Arabidopsis thaliana. AB - Gene targeting of a chromosomally integrated transgene in Arabidopsis thaliana is reported. A chimeric gene consisting of the promoter of the 35S RNA of CaMV, the polyadenylation signal of the octopine synthase gene and the coding region of the bacterial hygromycin phosphotransferase gene (hpt), which was rendered non functional by deletion of 19 bp, was introduced into the genome of A. thaliana using Agrobacterium-mediated gene transfer. A total of 3.46 x 10(8) protoplasts isolated from 17 independent transgenic Arabidopsis lines harbouring the defective chimeric hpt gene were transformed via direct gene transfer using various DNA forms containing only the intact coding region of the hpt gene. Out of 150 hygromycin-resistant colonies appearing in the course of these experiments, four were the result of targeted recombination of the incoming DNA with the defective chromosomal locus as revealed by PCR and Southern blot analysis. Comparison with the number of transformants obtained when an hpt gene controlled by a promoter and terminator from the nopaline synthase gene was employed results in a maximal ratio of homologous to non-homologous transformation in A. thaliana of 1 x 10(-4). PMID- 1310520 TI - Lethal overproduction of the Escherichia coli nucleoid protein H-NS: ultramicroscopic and molecular autopsy. AB - The Escherichia coli hns gene, which encodes the nucleoid protein H-NS, was deprived of its natural promoter and placed under the control of the inducible lambda PL promoter. An hns mutant yielding a protein (H-NS delta 12) with a deletion of four amino acids (Gly112-Arg-Thr-Pro115) was also obtained. Overproduction of wild-type (wt) H-NS, but not of H-NS delta 12, resulted in a drastic loss of cell viability. The molecular events and the morphological alterations eventually leading to cell death were investigated. A strong and nearly immediate inhibition of both RNA and protein synthesis were among the main effects of overproduction of wt H-NS, while synthesis of DNA and cell wall material was inhibited to a lesser extent and at a later time. Upon cryofixation of the cells, part of the overproduced protein was found in inclusion bodies, while the rest was localized by immunoelectron microscopy to the nucleoids. The nucleoids appeared condensed in cells expressing both forms of H-NS, but the morphological alterations were particularly dramatic in those overproducing wt H NS; their nucleoids appeared very dense, compact and almost perfectly spherical. These results provide direct evidence for involvement of H-NS in control of the organization and compaction of the bacterial nucleoid in vivo and suggest that it may function, either directly or indirectly, as transcriptional repressor and translational inhibitor. PMID- 1310521 TI - Cytochrome c1 from potato: a protein with a presequence for targeting to the mitochondrial intermembrane space. AB - Here we report the primary structure of potato cytochrome c1, a nuclear-encoded subunit of complex III. Using heterologous antibodies directed against cytochrome c1 from yeast two types of clones were isolated from an expression library, suggesting that at least two different genes are present and expressed in the genome. Northern blot analysis reveals that slightly varying levels of cytochrome c1 transcripts are present in all potato tissues analysed. A 1304 bp insert of one of the cDNA clones (pC13II) encodes the entire 320 amino acids of the precursor protein corresponding to a molecular weight of 35.2 kDa. As revealed by direct amino acid sequence determination of the cytochrome c1 protein another cDNA clone (pC18I) encodes the major form of cytochrome c1 present in potato tuber mitochondria. Western blots of subfractionated potato mitochondria show that the mature protein present in the membrane fraction is smaller than the pC13II encoded protein synthesized in Escherichia coli. The transient presequence of the protein is 77 amino acids long and has a bipartite polarity profile characteristic of presequences involved in targeting to the intermembrane space of fungal mitochondria. It consists of a positively charged NH2-terminal part which resembles "matrix targeting domains" and an adjacent hydrophobic region showing sequence similarities to "intramitochondrial sorting domains". The amino terminal region of potato cytochrome c1 is the first presequence of a plant protein of the mitochondrial intermembrane space to be determined and may be useful in the study of intramitochondrial sorting in plants. PMID- 1310522 TI - Alleviation of EcoK DNA restriction in Escherichia coli and involvement of umuDC activity. AB - The activity of the EcoK DNA restriction system of Escherichia coli reduces both the plating efficiency of unmodified phage lambda and the transforming ability of unmodified pBR322 plasmid DNA. However, restriction can be alleviated in wild type cells, by UV irradiation and expression of the SOS response, so that 10(3)- to 10(4)-fold increases in phage growth and fourfold increases in plasmid transformation occurred with unmodified DNA. Restriction alleviation was found to be a transient effect because induced cells, which initially failed to restrict unmodified plasmid DNA, later restricted unmodified phage lambda. Although the SOS response was needed for restriction alleviation, constitutive SOS induction, elicited genetically with a recA730 mutation, did not alleviate restriction and UV irradiation was still needed. A hitherto unsuspected involvement of the umuDC operon in this alleviation of restriction is characterized and, by differential complementation, was separated from the better known role of umuDC in mutagenic DNA repair. The need for cleavage of UmuD for restriction alleviation was shown with plasmids encoding cleavable, cleaved, and non-cleavable forms of UmuD. However, UV irradiation was still needed even when cleaved UmuD was provided. The possibility that restriction alleviation occurs by a general inhibition of the EcoK restriction/modification complex was tested and discounted because modification of lambda was not reduced by UV irradiation. An alternative idea, that restriction activity was competitively reduced by an increase in EcoK modification, was also discounted by the lack of any increase in the modification of lambda Ral-, a naturally undermodified phage. Other possible mechanisms for restriction alleviation are discussed. PMID- 1310523 TI - Positive regulation of the LPD1 gene of Saccharomyces cerevisiae by the HAP2/HAP3/HAP4 activation system. AB - The LPD1 gene of Saccharomyces cerevisiae, encoding lipoamide dehydrogenase (LPDH), is subject to catabolite repression. The promoter of this gene contains a number of motifs for DNA-binding transcriptional activators, including three which show strong sequence homology to the core HAP2/HAP3/HAP4 binding motif. Here we report that transcription of LPD1 requires HAP2, HAP3 and HAP4 for release from glucose repression. In the wild-type strain, specific activity of LPDH was increased 12-fold by growth on lactate, 10-fold on glycerol and four- to five-fold on galactose or raffinose, compared to growth on glucose. In hap2, hap3 and hap4 null mutants, the specific activities of LPDH in cultures grown on galactose and raffinose showed only slight induction above the basal level on glucose medium. Similar results were obtained upon assaying for beta galactosidase production in wild-type, or hap2, hap3 or hap4 mutant strains carrying a single copy of the LPD1 promoter fused in frame to the lacZ gene of Escherichia coli and integrated at the URA3 locus. Transcript analysis in wild type and hap2 mutants confirmed that the HAP2 protein regulates LPD1 expression at the level of transcription in the same way as it does for the CYC1 gene. Site directed mutagenesis of the putative HAP2/HAP3/HAP4 binding site at -204 relative to the ATG start codon showed that this element was required for full derepression of the LPD1 gene on non-fermentable substrates. PMID- 1310524 TI - Cloning and nucleotide sequence of the Escherichia coli K-12 ppsA gene, encoding PEP synthase. AB - We have cloned and sequenced the Escherichia coli K-12 ppsA gene. The ppsA gene codes for PEP synthase, which converts pyruvate into phosphoenolpyruvate (PEP), an essential step in gluconeogenesis when pyruvate or lactate are used as a carbon source. The open reading frame consists of 792 amino acids and shows homology with other phosphohistidine-containing enzymes that catalyze the conversion between pyruvate and PEP. These enzymes include pyruvate, orthophosphate dikinases from plants and Bacteroides symbiosus and Enzyme I of the bacterial PEP:carbohydrate phosphotransferase system. PMID- 1310526 TI - Congenital cytomegalovirus disease--20 years is long enough. PMID- 1310525 TI - The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. AB - BACKGROUND: Intrauterine transmission of cytomegalovirus (CMV) can occur whether a mother has prior immunity or acquires CMV for the first time during pregnancy. The degree of protection afforded an infected infant by the presence of antibody in the mother before conception is uncertain. METHODS: We compared the outcomes of CMV-infected infants born to mothers who acquired primary CMV infection during pregnancy (primary-infection group) with those of CMV-infected infants born to mothers with immunity (recurrent-infection group). Screening for viruria identified 197 newborns with congenital CMV infection. Stored serum samples were used to categorize maternal infection as either primary or recurrent. We followed 125 infants from the primary-infection group and 64 from the recurrent-infection group. Serial medical, audiologic, psychometric, and eye examinations were used to identify sequelae of CMV infection. RESULTS: Only infants in the primary infection group had symptomatic CMV infection at birth (18 percent). After a mean follow-up of 4.7 years, one or more sequelae were seen in 25 percent of the primary-infection group and in 8 percent of the recurrent-infection group. Thirteen percent of infants whose mothers had primary infection during pregnancy had mental impairment (IQ less than or equal to 70), as compared with none of those whose mothers had recurrent CMV infections. Sensorineural hearing loss was found in 15 percent of those in the primary-infection group and in only 5 percent of those in the recurrent-infection group. Bilateral hearing loss was identified only among children in the primary-infection group (8 percent). CONCLUSIONS: The presence of maternal antibody to CMV before conception provides substantial protection against damaging congenital CMV infection in the newborn. Primary maternal infection during pregnancy is associated with more severe sequelae of congenital CMV infection. PMID- 1310527 TI - [Progressive multifocal leukoencephalopathy in a female patient with chronic lymphatic leukemia]. AB - This case report describes a 78-year old female patient with chronic lymphocytic leukaemia and neurological symptoms due to progressive multifocal leukoencephalopathy (PML). At autopsy the histopathology was characteristic, the involvement of JC virus was established. PML occurs in immunocompromised patients and is caused by infection with JC papova virus. Epidemiology, clinical course, diagnostic procedures with special reference to the use of the polymerase chain reaction, and therapy are briefly reviewed. PMID- 1310528 TI - Demyelinating disease after neurologically complicated primary Epstein-Barr virus infection. AB - This report describes five patients who, following a neurologically complicated primary Epstein-Barr virus infection, developed progressive or relapsing neurologic deficits. The sequelae in four patients followed 4 to 12 years led to the diagnosis of multiple sclerosis (MS). The fifth patient presented with acute disseminated sclerosis and exhibits diffuse neurologic deficits that have persisted for 2 years. We suggest that the diagnosis of an unexplained acute neurologic or psychiatric syndrome should raise the question of a primary EBV etiology. A precisely timed serologic and hematologic study of the blood is imperative to capture the essential evidence. The data presented represent a clinical association between a neurologically complicated primary EBV infection and both chronic and acute demyelinating disease. The evidence does not justify a conclusion that EBV virus causes MS. PMID- 1310529 TI - Clinical and electrophysiologic findings in chronic neuropathy of Lyme disease. AB - We evaluated 25 patients with Lyme disease and chronic peripheral neuropathy. All had immunologic evidence of exposure to Borrelia burgdorferi and no other identifiable cause of neuropathy. Neuropathic symptoms began a median of 8 months (range, 0 to 165) after erythema migrans and had been present for a median of 12 months (range, 2 to 168) prior to evaluation. Twelve patients (48%) had generally symmetric distal, nonpainful paresthesia, and another 12 (48%) had generally asymmetric radicular pain. One patient (4%) had asymptomatic neuropathy. The most common physical finding was multimodal sensory loss, which was observed in 13 patients (52%); weakness and hyporeflexia were less common. Motor or sensory nerve conduction was slightly slow in 16 patients (64%). The paresthesia group more often had abnormalities on physical examination and on nerve conduction testing than did the radicular group. In 75% to 80% of patients from both groups, however, needle examination showed denervation in paraspinal and limb muscles. Among 20 patients who underwent lumbar puncture, only one had a slight spinal fluid pleocytosis. Six months after treatment with intravenous ceftriaxone, 19 patients (76%) were clinically improved. We conclude that Lyme disease can be associated with a reversible, mild chronic axonal sensorimotor polyradiculoneuropathy or polyradiculopathy. PMID- 1310530 TI - Cholesterol emboli neuropathy. AB - We report the clinical and pathologic features of a patient with peripheral neuropathy that was the first clinical expression of cholesterol emboli syndrome (CES). Biopsy of skeletal muscle and peripheral nerve revealed cholesterol clefts in lumens of small arteries, necrotizing arteritis, and severe degeneration of peripheral and intramuscular nerves. At autopsy, the peripheral nervous system was extensively affected by similar changes. We conclude that (1) peripheral neuropathy may be the initial manifestation of CES. Presumably, deposition of cholesterol leads to arteritis. (2) The underlying pathology of CES neuropathy is chronic axonal degeneration, possibly due to chronic ischemia of epineurial arteries. (3) Muscle biopsy is important in the antemortem diagnosis of CES. Nerve biopsy may show involvement of epineurial vessels. (4) CES may resemble polyarteritis nodosa clinically and pathologically. (5) CES may be under recognized and should be included in the differential diagnosis of any neuropathy of uncertain cause, particularly when there is a history of vascular catheterization, or severe aortic atherosclerosis. PMID- 1310532 TI - Immunocytochemical localization of ubiquitin in inclusion body myositis allows its light-microscopic distinction from polymyositis. PMID- 1310531 TI - Linkage of atypical myotonia congenita to a sodium channel locus. AB - We performed linkage analysis in a pedigree segregating an allele for autosomal dominant, painful myotonia that is potassium sensitive and responsive to acetazolamide. This allele was tightly linked to a skeletal-muscle, sodium channel locus which is now a candidate for the site of the mutational defect in acetazolamide-responsive myotonia congenita. Since this sodium channel locus is completely linked to the disease allele in all hyperkalemic periodic paralysis and paramyotonia congenita pedigrees studied, the molecular alteration causing acetazolamide-responsive myotonia congenita is likely an allelic defect in this human, skeletal-muscle, sodium channel gene. PMID- 1310533 TI - Brachial plexopathy associated with interleukin-2 therapy. PMID- 1310534 TI - Cramp-fasciculation syndrome. PMID- 1310535 TI - Renal tumors in childhood. AB - A great variety of tumors and tumor-like lesions affect the kidneys in childhood. We have discussed the practical aspects of the examination of tumors because the pathologist's role is becoming more critical to the staging and management of these patients. The use of newer techniques shows promise in renal tumors, and flow cytometry with DNA ploidy analysis may prove useful in more precisely identifying high-risk patients. Invaluable data continue to be generated from the large cooperative groups, particularly the National Wilms' Tumor Study, which helps refine our understanding of the renal tumors and their proper management. Close collaboration between the oncologist, the radiologist, the surgeon, the pathologist, and the radiation oncologist is the mainstay in providing the best possible outcome for these patients. PMID- 1310536 TI - Association of Epstein-Barr virus with human neoplasia. PMID- 1310537 TI - Role of cGMP and cGMP-dependent protein kinase in nitrovasodilator inhibition of agonist-evoked calcium elevation in human platelets. AB - Most platelet agonists activate and elevate the cytosolic free calcium concentration in human platelets through receptor-dependent mechanisms that are antagonized by cAMP- and cGMP-elevating agents. Nitrovasodilators such as nitroprusside and endothelium-derived relaxing factor are potent cGMP-elevating platelet inhibitors. In the present study, the role of cGMP and cGMP-dependent protein kinase in nitrovasodilator inhibition of ADP- and thrombin-evoked calcium elevation and activation of human platelets was investigated. Preincubation of platelets with 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-pCPT cGMP; a membrane-permeant selective activator of the cGMP-dependent protein kinase that does not significantly affect cGMP-regulated phosphodiesterases) inhibited the thrombin-induced phosphorylation mediated by myosin light chain kinase and protein kinase C. Nitrovasodilator-induced protein phosphorylation in human platelets was distinct from that induced by cAMP-elevating prostaglandins and could be mimicked by 8-pCPT-cGMP. Preincubation of human platelets with nitrovasodilators or 8-pCPT-cGMP inhibited the ADP- and thrombin-evoked calcium elevation in the presence and absence of external calcium. Nitrovasodilators and 8-pCPT-cGMP also inhibited the agonist-induced Mn2+ influx, but stopped-flow experiments indicated that the ADP receptor-operated cation channel was not significantly inhibited. These results suggest that in human platelets nitrovasodilators inhibit the agonist-induced calcium mobilization from intracellular stores and the secondary store-related calcium influx but not the ADP receptor-operated cation channel. The results also suggest that these nitrovasodilator effects are mediated by cGMP and the cGMP-dependent protein kinase. PMID- 1310538 TI - c-Jun represses the human insulin promoter activity that depends on multiple cAMP response elements. AB - Glucose is known to increase the cAMP concentration in pancreatic beta cells. To determine the mechanism by which cAMP augments insulin gene expression, we first identified the cAMP response elements (CREs) of the human insulin gene. In DNase I footprint analysis, the bacterially synthesized CRE-binding protein, CRE-BP1, protected four sites: two sites in the region upstream from the insulin core promoter, one site in the first exon, and one site in the first intron. To examine the roles of those four sites, we constructed a series of DNA plasmids in which the wild-type and mutant insulin promoters were linked to the chloramphenicol acetyl-transferase gene. Studies of the transcriptional activity of these plasmids after transfection into hamster insulinoma (HIT) cells showed that these four sites contributed additively to the cAMP inducibility of the insulin promoter. Surprisingly, the c-jun protooncogene product (c-Jun) repressed the cAMP-induced activity of the insulin promoter in a cotransfection assay with the c-Jun expression plasmid. Northern blot analysis demonstrated that the level of c-jun mRNA was dramatically increased by glucose deprivation in HIT cells. These results suggest that glucose may regulate expression of the human insulin gene through multiple CREs and c-Jun. PMID- 1310539 TI - Enzymatic catalysis and dynamics in low-water environments. AB - Enzymes suspended in organic solvents represent a versatile system for studying the involvement of water in enzyme structure and function. Addition of less than 1% (vol/vol) water to tetrahydrofuran containing 1 M 1-propanol leads to a substantial increase in the transesterification activity of subtilisin Carlsberg (from Bacillus licheniformis) that correlates with a sharp increase in the active site polarity and a 90% decrease in the rotational correlation time (i.e., increase in mobility) of a nitroxide spin label within the active site. Water in excess of 1% has little additional effect on active-site polarity and coincides with a further increase in spin-label mobility, yet the transesterification activity decreases dramatically. Thus, transesterification activity increases and then decreases with increasing enzyme hydration and flexibility (which are presumably coupled through dielectric screening), suggesting that the conformation of partially hydrated subtilisin is different from that of the nearly dry enzyme--i.e., enzyme containing less than 9% (wt/wt) water. PMID- 1310540 TI - Overexpression of an Aplysia shaker K+ channel gene modifies the electrical properties and synaptic efficacy of identified Aplysia neurons. AB - Although potassium channels play a variety of roles in shaping the electrical properties of neurons, little is known about how these channels are constituted in neurons. To examine the assembly and physiological function of A-type K+ channels in mature differentiated neurons, we have developed a highly efficient gene transfer method for Aplysia neurons that has allowed us to express about 10(7) copies of the cloned Aplysia Shaker (Sh) K+ channel (AK01a) in single identified cells. We find that expression of AK01a phenocopies one of the native transient K+ currents (IAdepol), suggesting that the native channel carrying IAdepol is assembled as a homooligomer of AK01a. Overexpression of AK01a has substantial effect on the action potential, shortening its duration, enhancing its hyperpolarizing afterpotential, and depressing by more than half the amount of transmitter release by the action potential from the terminals. Thus, the AK01a channel not only contributes to the firing properties within a given neuron but also can regulate the signaling between interconnected cells. PMID- 1310541 TI - Studies on the initiation of simian virus 40 replication in vitro: RNA primer synthesis and its elongation. AB - DNA primase-dependent synthesis of oligoribonucleotides 10-15 nucleotides long was observed in the presence of ATP, UTP, GTP, and CTP by using the purified components of the simian virus 40 (SV40) DNA replication system. The DNA primase catalyzed reaction required the SV40 large tumor antigen (T antigen), DNA polymerase alpha (pol-alpha), the three-subunit human single-stranded DNA binding protein (HSSB), and topoisomerase I. The synthesis of small RNAs was unaffected by the addition of activator 1, proliferating cell nuclear antigen, and DNA polymerase delta, proteins that can support extensive leading-strand synthesis. The RNA primers were derived predominantly from transcription of the lagging strand template, even after prolonged incubation, indicating that the leading strand did not serve as a template. When the four dNTPs were added after oligoribonucleotide synthesis, pol-alpha extended the RNA primers hybridized to SV40 DNA. Pulse-chase experiments revealed that the small RNA chains were elongated to Okazaki-sized products. T7 DNA polymerase was also shown to rapidly extend oligoribonucleotide primers in the presence of aphidicolin or antibodies against pol-alpha, conditions under which pol-alpha was markedly inhibited. These findings suggest that interactions between T antigen, pol-alpha-primase, and HSSB position the pol-alpha-primase complex on the lagging-strand template for RNA primer synthesis. PMID- 1310542 TI - Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups. AB - In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2 (hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta (2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models. PMID- 1310543 TI - Metabolism of glyceryl trinitrate to nitric oxide by endothelial cells and smooth muscle cells and its induction by Escherichia coli lipopolysaccharide. AB - Here, we demonstrate that the metabolism of glyceryl trinitrate (GTN) to nitric oxide (NO) occurs not only in bovine aortic smooth muscle cells (SMCs) but also in endothelial cells (ECs) and that this biotransformation is enhanced by pretreatment with Escherichia coli lipopolysaccharide (LPS). Two bioassay systems were used: inhibition of platelet aggregation and measurement of cGMP after stimulation by NO of guanylate cyclase in SMCs or ECs. In addition, NO produced from GTN by cells was measured as nitrite (NO2-), one of its breakdown products. Indomethacin (10 microM)-treated SMCs or ECs enhanced the platelet inhibitory activity of GTN. This effect was abrogated by coincubation with oxyhemoglobin (oxyHb; 10 microM), indicating release of NO from GTN. LPS (0.5 microgram/ml; 18 h) enhanced at least 2- to 3-fold the capacity of SMCs or ECs to form NO from GTN, and this enhancement was attenuated when cycloheximide (10 micrograms/ml) was incubated together with LPS. Furthermore, when incubated with GTN (200 microM) SMCs or ECs treated with LPS (0.5 microgram/ml; 18 h) released more NO from GTN than nontreated cells as indicated by a much higher (8- to 9-fold) increase in the levels of cGMP. Exposure of SMCs to GTN (600 microM) for 30 min led to an increase in the levels of NO2- dependent on cell numbers, which was enhanced when SMCs were treated with LPS. Incubation of nontreated or LPS-treated cells with NG-monomethyl-L-arginine (300 microM; 60 min) did not influence the metabolism of GTN to NO. SMCs failed to enhance the antiplatelet activity of sodium nitroprusside. Anesthetized rats treated with an intraperitoneal injection of LPS (20 mg/kg) 18 h beforehand showed enhanced hypotensive responses to GTN (0.25-1 mg/kg). These effects were blocked by methylene blue (10 mg/kg) but not by indomethacin (3 mg/kg). LPS did not alter the hypotensive responses induced by phentolamine, verapamil, or SIN-1. Thus, both in vitro and in vivo, LPS induces the enzyme(s) metabolizing GTN to NO. PMID- 1310544 TI - Retrovirus insertion into herpesvirus in vitro and in vivo. AB - Retroviruses and herpesviruses are naturally occurring pathogens of humans and animals. Coinfection of the same host with both these viruses is common. We report here that a retrovirus can integrate directly into a herpesvirus genome. Specifically, we demonstrate insertion of a nonacute retrovirus, reticuloendotheliosis virus (REV), into a herpesvirus, Marek disease virus (MDV). Both viruses are capable of inducing T lymphomas in chickens and often coexist in the same animal. REV DNA integration into MDV occurred in a recently attenuated strain of MDV and in a short-term coinfection experiment in vitro. We also provide suggestive evidence that REV has inserted into pathogenic strains of MDV in the past. Sequences homologous to the REV long terminal repeat are found in oncogenic MDV but not in nononcogenic strains. These results raise the possibility that retroviral information may be transmitted by herpesvirus and that herpesvirus expression can be modulated by retroviral elements. In addition, retrovirus may provide a useful tool to characterize herpesviral function by insertional mutagenesis. PMID- 1310546 TI - Sexually transmitted viruses other than HIV and papillomavirus. AB - This review has focused on a select group of viruses that can be sexually transmitted. The viruses include the herpesviruses, hepatitis A virus, hepatitis B virus, delta virus, non-A, non-B hepatitis virus(es), and molluscum contagiosum. Their impact on the population alone or in association with HIV disease necessitates a clear understanding of their ability to cause infection and of the manifestations of these infections. Characterization of these particular pathogens and treatment have been discussed with respect to the most current data available. Despite the growing sophistication in the field, we are still limited in our endeavors to identify and manage many viral infections. Therefore, measures to prevent transmission are continually being evaluated in an attempt to minimize exposure to these pathogens. PMID- 1310545 TI - The free radical in pyruvate formate-lyase is located on glycine-734. AB - Pyruvate formate-lyase (acetyl-CoA:formate C-acetyltransferase, EC 2.3.1.54) from anaerobic Escherichia coli cells converts pyruvate to acetyl-CoA and formate by a unique homolytic mechanism that involves a free radical harbored in the protein structure. By EPR spectroscopy of selectively 13C-labeled enzyme, the radical (g = 2.0037) has been assigned to carbon-2 of a glycine residue. Estimated hyperfine coupling constants to the central 13C nucleus (A parallel = 4.9 mT and A perpendicular = 0.1 mT) and to 13C nuclei in alpha and beta positions agree with literature data for glycine radical models. N-coupling was verified through uniform 15N-labeling. The large 1H hyperfine splitting (1.5 mT) dominating the EPR spectrum was assigned to the alpha proton, which in the enzyme radical is readily solvent-exchangeable. Oxygen destruction of the radical produced two unique fragments (82 and 3 kDa) of the constituent polypeptide chain. The N terminal block on the small fragment was identified by mass spectrometry as an oxalyl residue that derives from Gly-734, thus assigning the primary structural glycyl radical position. The carbon-centered radical is probably resonance stabilized through the adjacent carboxamide groups in the polypeptide main chain and could be comparable energetically with other known protein radicals carrying the unpaired electron in tyrosine or tryptophan residues. PMID- 1310547 TI - Biology of genital tract human papillomaviruses. AB - A large number of HPV types infect humans. They infect squamous epithelia of the skin and mucous membranes. Infections are widespread in sexually active populations. Some HPV types have oncogenic potential. Infections with HPV-16, HPV 18, and some additional types are risk factors for cervical cancer. The HPV-6 and HPV-11 types are responsible for most of the genital condylomas and nearly all respiratory papillomas. The immunologic responses to HPVs are not well understood. PMID- 1310548 TI - Human papillomavirus--related diseases in the female patient. AB - Human papillomavirus (HPV) has been strongly associated with malignancy in the female lower genital tract. Because squamous-cell carcinoma of the cervix is preceded by a spectrum of easily detectable and treatable premalignant changes, it is very preventable. The management of the patient with an abnormal Papanicolaou smear and the treatment of cervical, vaginal, and vulvar disease are outlined. PMID- 1310549 TI - Human papillomavirus in the male patient. AB - Human papillomavirus is a double-stranded DNA virus associated with a broad spectrum of clinical states including condylomata acuminata, latent and subclinical infection (acetowhitening), Bowen's disease, and carcinoma of the penis and anus. The virus is transmitted by direct contact with site-subtype specificity; additional studies are needed to elucidate the exact transmissibility and disease course of HPV infection. The association of HPV-16 and HPV-18 with anogenital malignancy increases the importance of treating such infections and raises questions about the role of HPV in oncogenesis. Treatment modalities for HPV include cytotoxic agents, surgical excision, immunotherapy, and laser ablation. Success rates appear best for laser ablation of evident disease. No therapeutic modality appears superior for treating latent disease. The public health ramifications of HPV are vast and warrant investigation to further our scientific and clinical understanding of oncogenesis and its prevention. PMID- 1310550 TI - Dietary fibre: the effectiveness of a high bran intake in reducing renal calcium excretion. AB - Fifteen healthy women were given a standardized calcium-rich diet (1800 mg calcium/day) with or without 36 g bran for 5 days. A similar study was also carried out with rice, soy and wheat bran. Urine samples were also collected 24 h. With all brans renal calcium excretion decreased and renal oxalic acid excretion increased. However, influence of rice bran was statistically significant. After 5 days of consuming 36 g rice bran/day 14 of 15 subjects showed decreased calcium excretion, but increased oxalic acid excretion. Relative supersaturation with calcium oxalate, as a measure for the risk of calcium stone formation, increased after addition of all brans. PMID- 1310551 TI - RP-30A: new tracer for detection of changes in testicular blood flow in rat torsion model. AB - RP-30A is a radioactive tracer being evaluated for the detection of regional myocardial blood flow. This study compares RP-30A to technetium 99m pertechnetate as radioactive tracers for the detection of testicular blood flow changes in early testicular torsion. The left testis of adult male Sprague-Dawley rats was subjected to either thirty or sixty minutes of 720 degrees torsion. Injections of RP-30A or 99mTc-pertechnetate followed by sacrifice and scintillation counting of the testes was performed. No significant difference was detected between the torted testes and the right control testes in both groups receiving 99mTc pertechnetate and the thirty-minute group receiving RP-30A. The torted testes of the sixty-minute group receiving RP-30A revealed a significant difference (decrease) in uptake indicating that RP-30A may be a more sensitive tracer in detecting testicular blood flow changes in early testicular torsion. PMID- 1310552 TI - The E7 functions of human papillomaviruses in rat 3Y1 cells. AB - Among more than 60 human papillomavirus (HPV) genotypes, several HPVs are believed to be high risk because they are found in close association with cervical carcinoma. We compared the E7 genes from HPVs 1, 6b, 16, 18, and 33 for their transactivating, transforming, and mitogenic functions in a single cell line rat 3Y1. Whereas both the low-risk (1 and 6b) and the high-risk (16, 18, and 33) HPVs were transactivating for the adenovirus E2 promoter, only the high-risk HPVs were capable of focal transformation as assayed by an efficient method using the SR alpha-promoter and in conjunction with the HPV 16 E6 gene. The putative oncogenicity of HPVs appears to be reflected in vitro by the focal transformation, but not by the transactivation. Transient expression of the E7 genes controlled by the dexamethasone-responsive MMTV-LTR showed that the HPV 16 mutant E7s only with residual transforming activity were not mitogenic, but that, although the low-risk HPV E7s were less efficient, both the low-risk and high risk HPV E7s were capable of inducing cellular DNA synthesis. Probably, the capability to induce cell DNA synthesis is necessary but not sufficient for the E7-mediated focal transformation. PMID- 1310553 TI - A mutation in the catalytic domain of pp60v-src is responsible for the host- and temperature-dependent phenotype of the Rous sarcoma virus mutant tsLA33-1. AB - We have analyzed a host- and temperature-dependent mutant of Rous sarcoma virus in order to learn more about the nature of mutations which lead to a host range phenotype. We have cloned and sequenced the v-src genes from this mutant, tsLA33 1, and from its presumed parent, tsLA33. Both the tsLA33 and the tsLA33-1 pp60v src proteins contain multiple mutations. The tsLA33 v-src gene product has amino acid alterations at four positions. In the tsLA33-1 v-src gene product, two of these four mutations have reverted to wild type. We have constructed chimeras between the two mutant v-src gene products and between each mutant and the Prague A v-src gene product. To assess the contribution of each amino acid change to the transformation phenotypes of tsLA33 and tsLA33-1, we expressed the hybrid proteins in both chicken embryo fibroblasts and Rat-3 fibroblasts. Additionally, we have measured the protein tyrosine kinase activity of chimeras constructed between the tsLA33 and tsLA33-1 pp60v-src proteins. Our results indicate that mutations in the catalytic domain of each protein are the principal determinants of the transforming ability and protein tyrosine kinase activity of the tsLA33 and tsLA33-1 pp60v-src proteins. PMID- 1310554 TI - Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. AB - The long terminal repeat (LTR) of a retrovirus contains sequence elements that constitute a promoter for controlling viral gene expression in infected cells. We have examined regulation of LTR-directed gene expression in feline immunodeficiency virus (FIV), a T-lymphocytopathic lentivirus associated with a fatal AIDS-like disease in domestic cats. Two independent virus isolates, designated FIV-Petaluma and FIV-PPR, have been molecularly cloned and show greater than 85% sequence homology. Both clones (termed pF34 and pPPR) produce infectious virus after transfection of permissive feline cells. Basal promoter activity of the LTRs was measured in various cell lines in transient expression assays using plasmids containing the viral LTR linked to the bacterial chloramphenicol acetyltransferase gene. Both LTRs were strong promoters in several cell lines, although in some cell lines the pF34 LTR had four- to fivefold higher basal activity than the pPPR LTR. FIV LTR mutations affecting the first AP4 site, AP1 site, ATF site, or NF-kappa B site resulted in decreased basal activity of the FIV promoter. Mutational analysis also revealed a negative regulatory element. In cotransfection experiments, both pF34 proviral DNA and pPPR proviral DNA appeared to transactivate either the pF34 LTR or the pPPR LTR; however, levels of transactivation were very low. Cotransfection of both LTRs with FIV subgenomic clones containing various viral open reading frames resulted in low level or no transactivation. The LTRs of both FIV clones responded to cell activation signals in human T-lymphoid cells (Jurkat) treated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Promoter function of both FIV LTRs was also enhanced in cells treated with either forskolin, an inducer of intracellular cyclic-AMP (c-AMP), or dibutyryl c-AMP. Analysis of site-specific mutants showed that a potential AP1 site in the U3 domain of the LTR was required for T-cell activation responses mediated by protein kinase C, whereas a putative ATF site was the target for c-AMP-induced responses mediated by protein kinase A. These studies revealed that cellular transcription factors play a significant role in regulation of FIV gene expression. PMID- 1310555 TI - The V5A13.1 envelope glycoprotein deletion mutant of mouse hepatitis virus type-4 is neuroattenuated by its reduced rate of spread in the central nervous system. AB - Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of less than 0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 10(4.2) PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS. PMID- 1310556 TI - Three transcriptionally distinct forms of Epstein-Barr virus latency in somatic cell hybrids: cell phenotype dependence of virus promoter usage. AB - Phenotypically distinct human B cell lines display two transcriptionally distinct forms of Epstein-Barr virus (EBV) latency. Latency I (Lat I) in group I Burkitt's lymphoma (BL) cell lines is characterized by selective expression of the virus coded nuclear antigen EBNA 1 from a uniquely spliced mRNA driven by the Fp promoter. Latency III (Lat III) in group III BL and EBV-transformed lymphoblastoid cell lines (LCLs) is characterized by expression of EBNAs 1, 2, 3a, 3b, 3c, and -LP from mRNAs driven by the Cp or Wp promoter and of the latent membrane proteins (LMPs 1, 2A, and 2B) from mRNAs driven by the LMP promoters. Here we have altered the group I BL and LCL phenotypes by cell hybridization and screened for attendant changes in EBV latency by PCR analysis of viral mRNAs and immunoblotting of viral proteins. Fusion of group I BL cells with LCLs activated the BL virus genome from a Lat I to Lat III pattern of gene expression. Fusion of LCLs with nonlymphoid lines repressed virus gene expression from Lat III either to Lat I or to another form of latency (Lat II) hitherto not seen in vitro and characterized by selective expression of the Fp-driven EBNA 1 mRNA and of the LMP 1, 2A, and 2B transcripts. There are therefore three forms of EBV latency which can be interconverted by altering cellular phenotype and thereby virus promoter usage. PMID- 1310557 TI - Cleavage of concatemeric DNA at the internal junction of "translocation" mutants of pseudorabies virus and inversion of their L component appear to be linked. AB - When pseudorabies virus (PrV) strains are grown in chicken embryo fibroblasts (CEF), variants ("translocation" mutants) arise in which there is a duplication of the leftmost sequences of the genome and their translocation in inverted orientation next to the internal inverted repeat bracketing the S component. In these variants, the UL becomes bracketed by inverted repeats and is found in two orientations relative to the Us. To study the cis-functions involved in cleavage of concatemeric DNA as well as those involved in inversion of the L component and to ascertain whether the two events are linked in the "translocation" mutants, a viral mutant (vLD68) was constructed in which the terminal 64 bp of the L component (that include sequences with homology to the pac 2 site of HSV) and the 4 terminal bp of the S component were deleted from the internal junction. Although revertants that have acquired the 68 bp at the internal junction emerge rapidly in populations of vLD68, analysis of the characteristics of this mutant revealed that: (1) the termini derived from both orientations of the L component include the 64 bp that have been deleted from the internal junction of vLD68; (2) in contrast to other "translocation" mutants, the internal junction of the vLD68 genome is not a good substrate for cleavage; (3) inversion of the L component of true vLD68 DNA does not occur or is rare; a good correlation exists in the populations of vLD68 between the proportion of revertants that have acquired an intact internal junction and the proportion of genomes with an L component that inverts. These results show that an intact internal junction in "translocation" mutants is necessary for both inversion of their L components and cleavage at their alternative internal junction. Since cleavage at the alternative junction will result in inversion of the L component, we conclude that inversion of the L component of "translocation" mutants of PrV can be attributed to cleavage of concatemeric DNA at the internal alternative junction. PMID- 1310558 TI - SV40 large T antigen trans-activates the long terminal repeats of a large family of human endogenous retrovirus-like sequences. AB - The Simian Virus 40 (SV40) large T antigen (T) is required for the initiation of viral replication, the autoregulation of early gene expression, and the activation of late gene expression in productively infected cells. In addition to these roles, T has been implicated in the transcriptional activation of a variety of viral and cellular promoters. We have used the chloramphenicol acetyltransferase (CAT) reporter gene system to study the effect of T on the long terminal repeats (LTRs) of a large family of human endogenous retrovirus-like sequences, RTVL-H. Here we show that T can activate expression from certain RTVL H LTRs 5- to 30-fold. Competition experiments in which an excess of plasmid containing only an RTVL-H LTR was cotransfected with an LTR-CAT reporter gene construct confirmed that this effect is specific for RTVL-H sequences. Restriction enzyme analysis using methylation-sensitive enzymes has shown that this activation is not due to plasmid replication. We have also observed this trans-activation effect in two CV-1 cells lines containing stably integrated LTR CAT constructs. These results demonstrate that a known transforming protein can alter the transcriptional capabilities of RTVL-H LTRs. As there are approximately 3000 related LTRs in the genomes of humans and other primates, these findings suggest that a large number of these promoters and their associated transcripts may be transcriptionally stimulated by this and other oncogens. PMID- 1310559 TI - Replication, latent infection, and reactivation in neuronal culture with a herpes simplex virus thymidine kinase-negative mutant. AB - Herpes simplex virus type 1 (HSV-1) mutant viruses lacking functional viral thymidine kinase activity are reported to be incapable of replication in neurons. To investigate the role of viral thymidine kinase (TK) activity in the HSV-1 infection of the neuron, we studied a thymidine kinase-negative (TK-) mutant virus engineered to eliminate TK function without affecting the other known transcripts encoded in this region of the genome. Studies using the mouse eye model demonstrated that the mutant behaved as is reported for other TK- viruses: DNA of the mutant virus was detected in the ganglia during the latent infection by polymerase chain reaction, but virus did not reactivate after explantation of the ganglia. Utilizing the neuronal cultures, we investigated the ability of the mutant virus to replicate in neurons and the capacity of the mutant virus to establish latency and reactivate. With a low multiplicity of infection (m.o.i.), replication of the TK- mutant virus in sensory neurons in culture was significantly delayed compared to that of the wild-type virus. However, when a high m.o.i. was used, the mutant and the wild-type viruses replicated with similar kinetics. The TK- mutant virus was capable of establishment of latency and reactivation from the latent infection in sensory neurons in culture. These data suggest that HSV-1 thymidine kinase activity facilitates viral replication, but that TK activity is not essential for either replication or reactivation from latent infections in neurons in vitro. PMID- 1310561 TI - Sex-related responses of beta-endorphin, ACTH, GH and PRL to cold exposure in humans. AB - To establish a possible different reaction between the male and the female to short-term exposure to cold, thermal, cardiovascular and pituitary hormonal responses to cold stress were measured in eight normal men and eight women (ages 19-24). The women were eumenorrheic and were tested in the follicular phase. Each subject, lightly clad, was required to remain for 30 min in a room at an ambient temperature of 25 degrees C followed by a 30 min period in a cold room at 4 degrees C. A month later, control tests were carried out at a constant 25 degrees C temperature for 1 h in the same subjects. Skin temperature, heart rate, blood pressure and plasma levels of beta-endorphin, ACTH, cortisol, GH and PRL were measured before and after cold exposure in the two groups. Before the test, all examined parameters were similar in the two groups. During cooling, blood pressure rose and pulse rate decreased significantly in the men, but not in the women, whereas skin temperature dropped in both groups. However, after cold exposure skin temperature was significantly lower in the women than in the men. A slight, but not significant increase in beta-endorphin, ACTH, cortisol and GH levels was observed after cooling in the men, whereas the women showed significant increments of these hormones. When values of skin temperature were combined with the differential (after minus before cold test) hormonal values, significant negative correlations were found for beta-endorphin, ACTH, cortisol and GH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310562 TI - Neonatal ovariectomy and pituitary-adrenal responsiveness in the adult rat. AB - Litters of female rat pups were handled daily from birth to weaning. When 12 days old the pups were ovariectomized or received sham surgery. At 70 days sham and ovariectomized animals were decapitated immediately or placed within a novel environment for 10, 20, or 40 min before decapitation. Basal plasma levels of androstenedione in ovariectomized animals were approximately half that of intact sham controls, and stress caused only a small rise in androstenedione in this group. Androstenedione levels in ovariectomized animals were consistently at or below the lower sensitivity of the radioimmunoassay, indicating that circulating levels of androstenedione in the female rat are primarily of ovarian origin. Basal ACTH and corticosterone levels did not differ significantly between the two groups. However, stress-induced levels of ACTH and corticosterone were significantly depressed in ovariectomized subjects compared to controls following exposure to the novel environment. Furthermore, while ACTH levels started to return to baseline by 40 min in controls, this effect was not observed in ovariectomized animals. These findings demonstrate that prepubertal removal of ovarian humoral factors can have a long-term impact on the responsiveness of the hypothalamic-pituitary-adrenal axis to stress. PMID- 1310560 TI - Serum levels of intact parathyroid hormone in elderly patients with hip fracture living at home. AB - The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7 +/- 15.9 vs 46.0 +/- 27.8 nmol/l) and calcitriol (63.6 +/- 25.0 vs 91.1 +/- 39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (4.7 +/- 2.1 vs 5.3 +/- 3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture. PMID- 1310563 TI - Thyrotropin action is impaired in the thyroid gland of old rats. AB - Aging in rats is characterized by low plasma concentrations of thyroid hormones with unchanged levels of TSH, suggesting an altered TSH action in addition to the impaired regulation of TSH secretion. To evaluate TSH action we determined TSH binding to thyroid membranes of young and old male rats (3-4 and 24-26 months of age), as well as the activity of adenylate cyclase in basal and stimulated conditions. Saturation analyses of [125I]-bTSH to thyroid membranes in the presence of increasing quantities of unlabelled bTSH (0.03-100 mU) show two types of binding sites, one of high affinity (Ka 1.5 10(9) mol l-1) the other of lower affinity (Ka 1.2 10(8) mol l-1), which are similar in both age groups. The number of TSH binding sites of high affinity is less in old rats than in young rats (7.6 +/- 0.9 vs 14.8 +/- 1.1 TSH mU/mg protein, N = 11 and 10 respectively, p less than 0.001), whereas the number of binding sites of low affinity is not significantly different (76.0 +/- 8.2 vs 99.1 +/- 9.0 TSH mU/mg protein). The activity of adenylate cyclase determined in basal conditions is similar in both old and young rats (1.11 +/- 0.12 vs 1.04 +/- 0.9 nmol cAMP/2 h x mg/protein). TSH (10 mU) induced a significant increase in cAMP formation with the thyroid membranes from young rats but not with those from old rats. In contrast, the stimulation of cAMP formation by GTP (2 mmol/l) or forskolin (10 mmol/l), two direct stimulators of adenylate cyclase, is similar in both groups of rats (200% and 250%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310564 TI - Regulation of cell growth, c-myc mRNA, and 1,25-(OH)2 vitamin D3 receptor in C3H/10T1/2 mouse embryo fibroblasts by calcipotriol and 1,25-(OH)2 vitamin D3. AB - Calcipotriol is a synthetic 1,25-(OH)2D3 analogue with high affinity for the 1,25 (OH)2D3 receptor, but with a lower affinity than 1,25-(OH)2D3 for vitamin D binding protein in serum. The inhibitory action of calcipotriol and 1,25-(OH)2D3 on proliferation of C3H/10T1/2 mouse embryo fibroblasts was examined in the non transformed cell line Cl 8 and in the two transformed, tumorigenic cell lines Cl 16 and TPA 482. Upon exposure to 10 nmol/l calcipotriol or 1,25-(OH)2D3, the proliferation of Cl 8 cell line was almost completely suppressed, whereas both hormones had no effect on the cell lines Cl 16 and TPA 482. Calcipotriol was at least as effective as 1,25-(OH)2D3 in inducing up-regulation of the 1,25-(OH)2D3 receptor. Displacement studies showed no difference between calcipotriol and 1,25 (OH)2D3 in the affinity for the receptor present in Cl 8 or Cl 16 cell extracts. Furthermore, the inhibition of cell growth in Cl 8 cells by calcipotriol was not accompanied by any consistent change in the steady-state expression of c-myc mRNA. In conclusion, calcipotriol had potent growth inhibitory effect on the non transformed cell line similar to 1,25-(OH)2D3. In the transformed cell lines, calcipotriol did not inhibit proliferation despite potent up-regulation of the 1,25-(OH)2D3 receptor. PMID- 1310565 TI - Ultrastructural alterations of the conduction system in mice exhibiting sinus arrest or heart block during Coxsackievirus B3 acute myocarditis. AB - By light and electron microscopy we studied the sinus nodes and atrioventricular (AV) conducting tissue of six C3H/He mice having coxsackievirus B3 acute myocarditis. Sinus arrest was documented in all six mice, and second- or third degree AV block was documented in three of the six mice. Although myocarditic changes in the conduction system, especially in the sinus node, were less than those in atrial and ventricular working myocardium, there were distinct abnormalities within both the sinus node and AV conducting tissue in all six hearts. Important ultrastructural alterations were inflammatory cell infiltrates and significant injury of specialized cells and of neural tissue. Specialized cells showed various features of degeneration and necrosis. Neural tissue damage included degeneration of axons and Schwann cells and disorganization of the neuromuscular junctions. Inflammatory cells, particularly macrophages, were often in intimate contact with injured specialized cells and neural tissue. Interstitial edema and bleeding and lymphatic vessel dilatation were also observed. These pathologic changes are considered to play an important role in the development of the documented disturbances of rhythm and conduction. PMID- 1310566 TI - Role of water-soluble dietary fiber in the management of elevated plasma cholesterol in healthy subjects. AB - Guidelines for the use of water-soluble dietary fibers (WSDF) in the dietary management of elevated plasma cholesterol are not well-established. Consequently, 4 studies were conducted to explore the plasma lipid-lowering effects of a variety of WSDF. Studies were randomized, double-blind, placebo-controlled trials involving healthy men and women (plasma cholesterol greater than 5.17 mmol/liter; greater than 200 mg/dl). Study duration ranged from 4 to 12 weeks. The WSDF acacia gum yields a low viscosity, palatable beverage when mixed in water. However, despite its WSDF classification, acacia gum consumed for 4 weeks as the sole WSDF source (15 g of WSDF/day) or primary source in a WSDF mixture (17.2 g of WSDF/day; 56% derived from acacia gum) did not produce a significant lipid lowering effect versus placebo. When 15 g of WSDF/day consisting of psyllium hust, pectin, and guar and locust bean gums (medium viscosity) was consumed for 4 weeks, significant reductions in cholesterol resulted (total cholesterol 8.3%, low-density lipoprotein cholesterol 12.4%; p less than 0.001) that were comparable to changes achieved with 10 g of WSDF/day from high-viscosity guar gum. The magnitude of the lipid-lowering effect was related to intake of WSDF ranging from 5 to 15 g/day (low-density lipoprotein cholesterol +0.8% [placebo], 5.6% [5 g/day], -6.8% [10 g/day], -14.9% [15 g/day]; p less than 0.01 for trend). The effects of WSDF on plasma lipids were similar for men and women. A diet rich in selected WSDF may be a useful adjunct to the dietary management of elevated plasma cholesterol. PMID- 1310567 TI - Youth at risk. Sex, drugs, and human immunodeficiency virus. AB - Adolescents and young adults are at risk for human immunodeficiency virus type 1 infection due to unprotected sexual intercourse and drug use. In 1988 and 1989, blinded surveys were conducted in 84 sexually transmitted disease clinics, 115 women's health clinics, and 19 drug treatment centers in 38 metropolitan areas. Blood specimens from 153,242 clients, aged 15 to 24 years, were tested for human immunodeficiency virus type 1 antibodies after all client identifiers were removed. In sexually transmitted disease clinics, the median rate was 0.4% among 15- to 19-year-olds, compared with 1.4% among 20- to 24-year-olds. Among heterosexual adolescents, rates in females were significantly higher than in males (Wilcoxon signed rank test). Rates in heterosexuals were highest in the northeastern and southeastern United States and in Puerto Rico. In 20- to 24-year old male clients in sexually transmitted disease clinics who had sex with males, rates ranged from 9.7% to 55.6%. In drug treatment centers, the median rate among 20- to 24-year-old men and women was 8.3% (range, 0% to 33.3%). Rates in women's health clinics were much lower (median, 0.1%). The high rates of infection in certain groups of adolescents and young adults indicate the need for improved care, education, and outreach targeted toward those at high risk. PMID- 1310568 TI - Clinical implications of herpesvirus infections in patients with AIDS. Introduction. PMID- 1310569 TI - Clinical implications of herpesvirus infections in patients with AIDS. Proceedings of a symposium. April 6, 1991, New York, New York. PMID- 1310570 TI - Characteristics of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. AB - Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). The disease is inexorably progressive when untreated, making early detection and prompt treatment essential for preservation of functional vision. The retinitis tends to be unilateral at presentation but often becomes bilateral as it progresses. Lesions may be unifocal or multifocal and may appear in the posterior retina or peripheral retina. Primary ophthalmoscopic features of CMV retinitis include white granular zones of retinal necrosis, variable degrees of associated hemorrhage, and low-grade iritis and vitritis. Differential diagnosis is aided by characteristic features of CMV retinitis and other AIDS-related retinopathies. Initial treatment with ganciclovir or foscarnet has been found to stabilize retinitis, and maintenance therapy with either has been shown to prolong the time to retinitis progression. Further studies should help to determine the optimal approach to treatment of the disease. PMID- 1310571 TI - Differential diagnosis of retinitis and choroiditis in patients with acquired immunodeficiency syndrome. AB - Patients with acquired immunodeficiency syndrome (AIDS) are at high risk for developing retinitis. The most common forms of retinitis in such patients are those caused by cytomegalovirus (CMV) and Toxoplasma; however, retinitis or choroiditis can also be caused by other viral, protozoal, bacterial, and fungal agents. Differential diagnosis of these infections is based on a number of factors, including ophthalmoscopic appearance, underlying disease, clinical history, and severity of underlying immunosuppression. Rapid and accurate diagnosis is essential in preserving functional vision, as some forms of retinitis are rapidly progressive and since appropriate treatment varies by diagnosis. PMID- 1310572 TI - Design of a randomized controlled trial of foscarnet in patients with cytomegalovirus retinitis associated with acquired immunodeficiency syndrome. AB - In a controlled trial of foscarnet in the treatment of cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS), patients with non-immediately sight-threatening lesions were randomized to receive immediate treatment with foscarnet or foscarnet treatment delayed until the first signs of retinitis progression. Foscarnet induction therapy was administered at a dosage of 60 mg/kg 3 times/day via 1-hour intravenous infusion for 21 days. Foscarnet maintenance therapy was administered at a dosage of 90 mg/kg/day via 2-hour infusion. Foscarnet was well tolerated and effective in delaying progression of CMV retinitis in these patients. Final analysis of data from this study and data from other studies will help to determine what role foscarnet will have in the treatment of CMV retinitis in patients with AIDS. PMID- 1310573 TI - Maintenance therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: foscarnet. AB - The use of ganciclovir in the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) is limited by marrow toxicity and by the development of resistance to this agent in CMV strains capable of causing progressive disease. Foscarnet retains activity against ganciclovir-resistant CMV and has an adverse effect profile different from that of ganciclovir. Preliminary data from studies conducted under the AIDS Clinical Trials Group (ACTG) program indicate that intravenous foscarnet maintenance therapy at 60, 90, and 120 mg/kg/day in AIDS patients with CMV retinitis successfully completing foscarnet induction therapy is associated with median times to retinitis progression of 90, 95, and greater than 123 days, respectively. An ACTG trial of foscarnet in patients failing ganciclovir therapy has been initiated, as has a trial jointly sponsored by the National Eye Institute and the National Institute of Allergy and Infectious Diseases comparing the safety and efficacy of foscarnet and ganciclovir. Also underway is a trial evaluating the effects of combination and alternating regimens of these two agents. PMID- 1310574 TI - Multiply charged negative ions by electrospray ionization of polypeptides and proteins. AB - Multiply deprotonated polypeptide and protein molecules, (M - nH)n-, produced from pH approximately 11 aqueous solutions, are analyzed by electrospray ionization-mass spectrometry (ESI-MS). Aqueous ammonium hydroxide solutions of the analyte are shown to be preferable to sodium hydroxide solutions for negative ion ESI due to the production of multiply sodiated protein species from the latter system. Proteins with Mr to 66,000 and having up to 57 negative charges have been detected. Multiply charged negative ions can be produced from ESI of the highly acidic protein pepsin (Mr approximately 34,600) because of its relatively large number of acidic residues, 42. In contrast, the small number of basic amino acid residues for pepsin (4) does not allow formation of highly protonated species essential for positive-ion detection, for mass spectrometers of limited m/z range. Similarly, negative-ion ESI-MS is extended to large oligosaccharide analysis. Preliminary tandem mass spectrometry experiments of multiply charged polypeptide anions demonstrate the utility and potential of negative-ion ESI-MS for structural elucidation. PMID- 1310575 TI - Enhanced superoxide production by alveolar macrophages and air-space cells, airway inflammation, and alveolar macrophage density changes after segmental antigen bronchoprovocation in allergic subjects. AB - Airway inflammation is a principal determinant of airway responsiveness and function in asthma and allergic diseases. Alveolar macrophages (AM) may contribute to inflammation in multiple ways, including release of reactive oxygen species such as superoxide (SO) anion. We hypothesized that SO production by AM increases after segmental bronchoprovocation (SBP) with relevant antigen and contributes to airway injury. Eight ragweed-sensitive subjects with allergic rhinitis were studied by bronchoalveolar lavage and ragweed SBP to determine the SO production and characteristics of cells recruited after antigen challenge. No significant changes in cell numbers or total protein concentration were observed immediately after antigen challenge. Purification (to greater than 94%) of AM on discontinuous gradients of Percoll revealed significantly increased spontaneous and opsonized-zymosan-driven SO production immediately after antigen challenge. Forty-eight hours later, total air-space cells, AM, eosinophils, and total protein concentration were significantly increased in relationship to antigen dose given. Furthermore, both unfractionated air-space cells and purified AM obtained 48 h after antigen challenge released increased amounts of SO anion in response to activator compared with either cells obtained immediately after SBP or those obtained 48 h after saline challenge. In addition, significant increases in high density AM were also seen 48 h after antigen challenge. These data suggest that AM activation occurs immediately after antigen challenge, and that the late airway response to antigen is characterized by the appearance of high density AM, which have potentiated SO release. The increased oxidative burden thereby produced may contribute to increased airway injury. PMID- 1310576 TI - Serum procollagen III peptide levels in subjects with sarcoidosis. A 5-year follow-up study. AB - In a prospective study, Type III procollagen N-terminal peptide was measured in the sera of 38 subjects with biopsy-proven pulmonary sarcoidosis at 6-month intervals over a period of 5 yr. The subjects were divided into four groups according to their radiologic presentation and clinical course: Group A (n = 10) subjects with sarcoidosis Type I without radiologic progression over 5 yr; Group B (n = 5) subjects with sarcoidosis Type I with radiologic progression to Stage II or III; Group C (n = 9) subjects with sarcoidosis Types II and III without progression over 5 yr; and Group D (n = 14) subjects with sarcoidosis Types II and III with radiologic progression. Lung function tests (FVC, FEV1, and DLCO), chest roentgenograms, and measurements of serum angiotensin converting enzyme (S ACE) were performed concurrently with the S-PCP-III levels. Significantly higher levels of S-PCP-III were found in group B (Type I, progressive) (18.2 +/- 1.09 ng/ml) and in group D (Type II/III, progressive) (13.9 +/- 1.2 ng/ml) compared with those of Group A (Type I, stable) (9.1 +/- 1.09 ng/ml) and Group C (Type II/III, stable) (7.6 +/- 1.1 ng/ml) or normal volunteers (9.4 +/- 4 ng/ml) (p less than 0.001 for all comparisons). Changes in S-PCP-III levels tended to parallel the clinical course, and steroid treatment resulted in a significant decrease in S-PCP-III concentrations (p less than 0.001). In contrast, serum angiotensin converting enzyme (S-ACE) levels did not correlate with either the clinical course or radiologic changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310577 TI - Tissue distribution and antifungal effect of liposomal itraconazole in experimental cryptococcosis and pulmonary aspergillosis. AB - We studied the tissue distribution and in vivo antifungal effect of itraconazole, incorporated into pure dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes and administered intravenously. Eighty percent of the itraconazole was associated with DPPC. Drug levels in lung, brain, and liver, obtained after intravenous administration of tritiated itraconazole, were higher when the drug was administered intravenously as liposomal than when it was dissolved in cyclodextrin. Administration of the liposomal formulation also led to higher and sustained levels of intact itraconazole in serum. Efficacy was assessed in DBA/2 mice infected intravenously with 3 x 10(6) Cryptococcus neoformans, an inoculum responsible for early fatal pneumonia, or 3 x 10(5) C. neoformans, leading to delayed meningitis. In pneumonia, 20 mg/kg of liposomal itraconazole was more effective on survival than the same dose given intravenously in cyclodextrin or twice the dose administered orally dissolved in polyethylene glycol 200. In meningitis, liposomal itraconazole was also more efficient than the drug dissolved in cyclodextrin. These results were confirmed by colony counts in the brain and lung of infected mice. In immunosuppressed OF1 mice infected after inhalation of Aspergillus fumigatus spores, liposomal itraconazole (20 mg/kg x 3) was the only effective treatment. We conclude that intravenous liposomal delivery of itraconazole enhances both concentrations in infected tissues and the in vivo efficacy of the drug. Such passive targeting of antifungal agents other than amphotericin B might be helpful in the treatment of severe systemic mycoses, especially in the case of lung or brain involvement. PMID- 1310578 TI - Angioedema after substituting lisinopril for captopril. PMID- 1310579 TI - Hepatitis C virus testing in African sera. PMID- 1310580 TI - Murine cytomegalovirus DNA polymerase: purification, characterization and role in the antiviral activity of acyclovir. AB - Murine cytomegalovirus (MCMV) neither induces a viral thymidine kinase (TK) nor enhances the activity of a cellular TK. Nevertheless, MCMV is highly susceptible to 9-(2-hydroxyethoxymethyl)guanine (acyclovir, ACV). The cellular TK is neither responsible for phosphorylation of ACV nor its anti-MCMV activity. This is clear from the findings that little ACV triphosphate is formed in MCMV-infected mouse embryo fibroblasts (MEF) and that the replication of MCMV is inhibited equally well by ACV in TK+ and TK- cells. Even if trace amounts of ACV triphosphate would be formed by enzymes other than TK, and ACV triphosphate would be responsible for the anti-MCMV activity of ACV, then the MCMV DNA polymerase ought to be highly sensitive to ACV triphosphate. To examine this possibility, the MCMV DNA polymerase was partially purified and characterized. The apparent Ki value of the MCMV DNA polymerase for ACV triphosphate indicates that the sensitivity of the MCMV DNA polymerase to ACV triphosphate is equivalent to that of the HSV DNA polymerase. Therefore, the trace amounts of ACV triphosphate that are formed in MCMV-infected MEF seem to be insufficient to inhibit MCMV DNA polymerase and may not play a key role in the anti-MCMV activity of ACV. PMID- 1310581 TI - Irreversible inhibition of human cytomegalovirus replication by topoisomerase II inhibitor, etoposide: a new strategy for the treatment of human cytomegalovirus infection. AB - We demonstrated previously that human cytomegalovirus (CMV) infections could enhance the expression of cellular topoisomerase II and this enzyme activity is essential for CMV to replicate in vitro (Benson and Huang, 1988; Benson and Huang, 1990). In this study, we further show that in addition to m-AMSA and VM26 which we had previously reported, a widely used and clinically available drug, etoposide (VP-16 or VePesid) can irreversibly inhibit CMV replication at the drug concentration (2.5 micrograms/ml) greatly below toxic levels to stationary phase cells. Growing cells were more sensitive to etoposide than stationary phase cells and slight growth inhibition occurred at 2.5 micrograms/ml level. This inhibitor does not prevent the expression of CMV immediate-early and early genes, but can inhibit viral DNA and late viral-proteins synthesis. Because of their irreversible inhibitory effects and approval usage in clinical oncology, it is suggested that this group of compounds, particularly etoposide (VP-16), can be used to control life-threatening CMV infections, such as CMV pneumonitis and CMV retinitis, in cancer and immunocompromised patients or patients with AIDS. PMID- 1310582 TI - Structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta D-arabinofuranosyluracil (BV-araU, V-araU) in inhibition of Epstein-Barr virus replication. AB - The structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1 beta-D-arabinofuranosyluracil (BV-araU and V-araU) in inhibition of Epstein-Barr virus (EBV) was evaluated. Both V-araU and BV-araU effectively inhibited EBV replication in virus-producer P3HR-1(LS) cells, as determined by DNA-DNA hybridization. The 50% effective doses (ED50) for viral DNA replication were 0.005 and 0.3 microM for V-araU and BV-araU, respectively. The in vitro therapeutic index was 4000 for V-araU and 1300 for BV-araU. Synthesis of EBV induced polypeptides with molecular weights of 145,000 (145, 140, 130, and 110 kDa) was significantly inhibited by both drugs. Only V-araU inhibited the synthesis of 85-, 55-, and 32-kDa polypeptides by approx. 50%. Kinetic analysis of inhibition and reversibility of EBV DNA replication after removal of the drugs indicated that BV-araU has a more prolonged inhibitory effect than V-araU. These results indicate that the substitution of H by Br in the 5-vinyl group results in marked reduction in anti-EBV activity while prolonging the drug effect and diminishing cytotoxicity. PMID- 1310583 TI - Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus. AB - A number of anthraquinones, anthrones and anthraquinone derivatives were evaluated for antiviral activity against human cytomegalovirus (HCMV) as well as for cytotoxicity. Of those compounds evaluated, quinalizarin, emodin, rhein, hypericin, protohypericin, alizarin, emodin bianthrone and emodin anthrone showed antiviral activity against a normal laboratory HCMV strain, AD-169. When tested against a ganciclovir-resistant strain of HCMV, the EC50 values for quinalizarin, rhein and alizarin were superior to the values obtained for the AD-169 strain of HCMV. These results suggest that these compounds will be useful as prototypes for synthesizing a class of anti-HCMV drugs that are effective against ganciclovir sensitive and -resistant strains of HCMV. PMID- 1310584 TI - Hereditary motor and sensory neuropathy with treatable extrapyramidal features. AB - Seven patients with a sensorimotor peripheral neuropathy followed years later by extrapyramidal manifestations are presented. This appears to be a separate genetic disorder(s) from that described as Machado-Joseph disease. In five subjects, other relatives had similar multisystem involvement. None was of known Portuguese ancestry. The extrapyramidal syndrome was mainly parkinsonian. Pain was prominent in five subjects. In all cases, low or moderate doses of levodopa/carbidopa ameliorated both the pain and the parkinsonian features. In one patient, a randomized placebo-controlled trial of levodopa/carbidopa was found to significantly improve most symptoms and neurologic dysfunction scores related to the extrapyramidal syndrome. PMID- 1310585 TI - Foreign-body giant-cell reaction to the hydroxyapatite orbital implant. PMID- 1310586 TI - Treatment of cytomegalovirus retinitis--1992. PMID- 1310587 TI - Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device. AB - A surgically implantable device for sustained intravitreal release of ganciclovir has been developed. The device delivers ganciclovir intraocularly over approximately 4 to 5 months. Eight patients with acquired immunodeficiency syndrome (AIDS) and associated cytomegalovirus (CMV) retinitis were recruited as part of a phase 1 study. Thirteen eyes with active CMV retinitis underwent surgical implantation of the ganciclovir device. All eyes showed resolution of the CMV retinitis; none showed progression. Visual acuity remained unchanged in three eyes, improved in six eyes, and decreased in four eyes. Surgical complications included mild vitreous hemorrhage, astigmatism, and suprachoroidal placement of the device. Retinal detachment occurred in three eyes as the retinitis resolved. This new intraocular drug delivery system offers many advantages compared with intravenous therapy or repeated intravitreal ganciclovir injections for the management of CMV retinitis in patients with AIDS. PMID- 1310588 TI - Intravitreal sustained-release ganciclovir. AB - Current treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome involves frequent intravenous administration of sodium ganciclovir that often results in unacceptable side effects. We have developed devices that release ganciclovir at rates of 2 micrograms/h and 5 micrograms/h in vitro. When implanted into the vitreous of rabbit eyes, mean intravitreal ganciclovir levels of 9 mg/L and 16 mg/L were maintained for more than 80 and 42 days, respectively. Devices were well tolerated, with no toxic effects attributable to the polymers used in the devices. This investigation indicates that these devices can maintain therapeutic levels of drug for extended periods and are well tolerated in the rabbit eye. They may prove useful in the clinical management of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. PMID- 1310589 TI - Receptor-mediated increases in cytosolic Ca2+ in the human erythroleukaemia cell line involve pertussis toxin-sensitive and -insensitive pathways. AB - The pluripotent human erythroleukaemia cell line, HEL, possesses erythrocytic, megakaryocytic and macrophage-like properties. With respect to signal transduction, HEL cells have been used as a model system for platelets, but little attention has been paid to their phagocytic properties. We studied the effects of various receptor agonists on the intracellular free Ca2+ concentration ([Ca2+]i) in HEL cells. Thrombin, platelet-activating factor (PAF), ATP, UTP, prostaglandins E1 and E2 (PGE1 and PGE2), the PGE2 analogue sulprostone and the stable PGI2 analogues iloprost and cicaprost increased [Ca2+]i. ADP was less effective than ATP, and UDP was unable to increase [Ca2+]i. The increases in [Ca2+]i induced by thrombin, PAF, ATP, UTP, iloprost and cicaprost were pertussis toxin-insensitive, whereas the increases induced by PGE2 and sulprostone were completely inhibited by the toxin. The increase in [Ca2+]i induced by PGE1 was partially inhibited by pertussis toxin. PGE2 did not desensitize the increase in [Ca2+]i induced by iloprost, and vice versa. PGE1 desensitized the response to PGE2 and iloprost but not vice versa. Adrenaline potentiated the iloprost- but not the PGE2-induced rise in [Ca2+]i. The phorbol ester phorbol 12-myristate 13 acetate completely blocked the rise in [Ca2+]i induced by ATP and PGE1, whereas the increases induced by thrombin and PAF were only partially inhibited. Agonists increased [Ca2+]i through release from internal stores and sustained Ca2+ influx. Thrombin stimulated Mn2+ influx, which was blocked by Ni2+. Diltiazem, isradipine, gramicidin and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4 methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365) did not affect agonist induced rises in [Ca2+]i. HEL cells contained substantial amounts of beta glucuronidase which, however, could not be released, and they did not aggregate or generate superoxide. Our data suggest that: (1) HEL cells possess nucleotide receptors with properties similar to those of phagocytes; (2) they possess receptors for PGE2 and PGI2, and PGE1 is an agonist at both receptors; (3) agonist-induced increases in [Ca2+]i are mediated through pertussis toxin sensitive as well as -insensitive signal transduction pathways; and (4) agonists increase [Ca2+]i by mobilization from internal stores and influx from the extracellular space through cation channels with properties similar to those of phagocytes and platelets. PMID- 1310590 TI - Evidence for a role of rap1 protein in the regulation of human platelet Ca2+ fluxes. AB - The relationship between the 22-24 kDa cyclic AMP (cAMP)-dependent phosphoprotein previously described as being involved in the regulation of human platelet membrane Ca2+ transport and a GTP-binding protein of low molecular mass (ras-like protein) was investigated. After isolation of plasma membranes and intracellular membranes, it was found that guanosine 5'-[gamma-thio]triphosphate (GTP[S]) bound to plasma membrane proteins ranging in molecular mass from 22 to 29 kDa, but not to intracellular membranes. The major GTP-binding protein appeared as a 24 kDa protein under reduced conditions and a 22 kDa protein under non-reduced conditions. A similar membrane location and electrophoretic mobility were found for both the cAMP phosphoprotein and the protein recognized by a specific anti rap1 antibody. The identity between the cAMP phosphoprotein and the rap1 GTP binding protein was further examined by studying the functional effect of GTP on plasma membrane Ca2+ transport. A maximal GTP[S] concentration of 40 microM was found to: (1) inhibit to the same degree (40%) both Ca(2+)-ATPase activity and the Ca2+ transport function mediated by the Ca(2+)-ATPase; (2) inhibit the phosphorylation of the 22-24 kDa protein by the catalytic subunit of the cAMP dependent protein kinase (C.Sub.); and (3) abolish the stimulation of Ca2+ uptake induced by C.Sub. It is concluded that the platelet cAMP phosphoprotein is indeed the rap1 GTP-binding protein, and that it regulates plasma membrane Ca2+ transport, thus providing evidence for a new role of a ras-related protein. PMID- 1310591 TI - Identification of a 80 kDa calmodulin-binding protein as a new Ca2+/calmodulin dependent kinase by renaturation blotting assay (RBA). AB - We surveyed rabbit brain cytosol for a new Ca2+/calmodulin (CaM)-dependent kinase. The renaturation blotting assay (RBA) exploits the ability of blotted SDS denatured proteins to regain enzymic activity after guanidine treatment. Using RBA, we found that the eluate of rabbit brain cytosol from a CaM affinity column contains at least four electrophoretically distinct protein kinase bands which were autophosphorylated in a Ca2+/CaM-dependent manner. The 49 kDa band and the 60 kDa band were alpha and beta subunit of CaM kinase II, and the 42 kDa band was presumed to be CaM kinase I, but the 80 kDa band could not be attributed to any reported Ca2+/CaM-dependent protein kinases. The 80 kDa protein kinase was isolated by three-step chromatography. We examined the phosphorylation of exogenous substrates by 80 kDa protein kinase, and histone IIIs and myosin light chain were phosphorylated in a Ca2+/CaM-dependent manner. W-7, a specific inhibitor for calmodulin, inhibited this kinase activity, but KN-62, a specific inhibitor for CaM kinase II, had no effect on this protein kinase activity. Autoradiography using boiled rabbit brain homogenate as substrate showed three intrinsic substrates (80 kDa, 60 kDa and 42 kDa), which were phosphorylated in a Ca2+/CaM-dependent manner. These findings suggest that a new Ca2+/CaM-dependent protein kinase could be identified by the RBA. PMID- 1310592 TI - Modulation of 1,25-dihydroxyvitamin D3-dependent Ca2+ uptake in skeletal muscle by protein kinase C. AB - In vitro studies have shown that short exposure (1-10 min) of vitamin D-deficient chick soleus muscle to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] causes an acute stimulation of tissue 45Ca uptake through voltage-gated Ca2+ channels, with parallel increases in cyclic AMP levels, adenylate cyclase activity and membrane protein phosphorylation. We further investigated the involvement of protein kinases in the rapid effects of 1,25(OH)2D3 on skeletal muscle. The hormone was found to stimulate the protein kinase C (PKC) activity of muscle membranes. The PKC activator phorbol 12-myristate 13-acetate (PMA, 100 nM) was found to rapidly stimulate muscle 45Ca uptake, mimicking 1,25(OH)2D3. Increases of 68% and 46% were observed at 1 and 15 min of exposure to PMA respectively. The effects of PMA were dose-dependent (50-200 nM) and were specific, since the inactive analogue 4 alpha-phorbol was without effect. Analogously to the effects of the sterol, PMA enhanced 45Ca uptake was abolished by the Ca2+ channel antagonists nifedipine (30 microM) and verapamil (50 microM). Staurosporine (10 nM), a PKC inhibitor, surprisingly potentiated 1,25(OH)2D3-dependent stimulation of 45Ca uptake. Exposure of skeletal muscle to PMA (100 nM) plus 1,25(OH)2D3 (1 nM) produced a less pronounced effect on 45Ca uptake than either agent alone. PMA also decreased muscle cyclic AMP levels. These results suggest a regulatory link between the two major transmembrane signalling systems in the mechanism of action of 1,25(OH)2D3 in skeletal muscle. PMID- 1310594 TI - Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II. AB - We investigated the binding properties of the type I insulin-like growth factor (IGF) receptor expressed in NIH-3T3 fibroblasts transfected with a human type I receptor cDNA. Cell surface receptors bound IGF-I with KD = 1 nM as predicted. Although recent studies have suggested that IGF-I and IGF-II bind to type I receptors with near-equal affinity, the receptors in this system bound IGF-II with much lower affinity (KD = 15-20 nM). When type I receptors from the transfected cells were solubilized and immunopurified, however, both 125I-IGF-I and 125I-IGF-II bound to the purified receptors with extremely high and relatively similar affinities (KD = 8 and 17 pM respectively). Thus the immunopurified receptors had higher affinity but lower specificity for the two ligands. The monoclonal antibody alpha IR-3 effectively inhibited IGF-I binding to cell surface receptors (75 +/- 10%), but did not inhibit IGF-II binding. In the purified receptor assay, alpha IR-3 also inhibited IGF-I binding more effectively than IGF-II binding (38 +/- 7% versus 10 +/- 4%). We conclude that the products of this cDNA can account for the binding patterns that we previously observed in receptors immunopurified from human placenta. The differential effect of alpha IR-3 on IGF-I versus IGF-II raises the possibility that these homologous growth factors bind to immunologically distinct epitopes on the type I receptor. PMID- 1310593 TI - The role of pancreatic hormones in the regulation of lipid storage, oxidation and secretion in primary cultures of rat hepatocytes. Short- and long-term effects. AB - Exposure of cultured rat hepatocytes to a high concentration of insulin (78 nM) for 24 h in the presence of extracellular oleate (0.75 mM) resulted in a decrease in the secretion of apoprotein B (apoB) and triacylglycerol associated with very low-density lipoprotein (VLDL). However, continuous exposure of the cells to insulin for longer periods (72 h) stimulated the secretion of apoB and triacylglycerol. Treatment of hepatocytes with glucagon (0.1 microM) for 24 h also suppressed the secretion of VLDL apoB, cholesterol and triacylglycerol. The cells remained responsive to the inhibitory effect of glucagon for at least 3 days. In contrast with insulin, however, exposure of the cells to glucagon for a continuous period of 72 h did not lead to a reversal of the initial inhibition. Glucagon also stimulated ketogenesis, and in this regard the cells were responsive for at least 3 days in culture. These changes were accompanied by a transient increase in intracellular cyclic AMP (cAMP) concentration, which reached a peak 10 min after addition of glucagon. Between 12 h and 24 h after glucagon addition, cAMP levels had returned almost to normal, but the secretion of VLDL remained suppressed during this period. PMID- 1310595 TI - Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide. AB - Both nitric oxide (NO) and superoxide are generated by macrophages, neutrophils and endothelial cells. It has been postulated that the generation of these two radicals under physiological conditions can lead to the formation of peroxynitrite and (as a result of the homolytic lysis of this molecule) the production of hydroxyl radicals. We have used 3-morpholinosydnonimine N ethylcarbamide (SIN-1), a sydnonimine capable of generating both NO and superoxide simultaneously, to test this hypothesis. SIN-1 (1 mM) generated superoxide and NO at rates of 7.02 microM/min and 3.68 microM/min respectively in phosphate-buffered saline, pH 7.2, at 37 degrees C. Incubation of SIN-1 with both deoxyribose and sodium benzoate resulted in the formation of malondialdehyde (MDA). In addition, the incubation of SIN-1 with sodium benzoate resulted in the production of compounds with fluorescence emission spectra characteristic of hydroxylated products. Both the production of MDA and the generation of fluorescent compounds were inhibited by the hydroxyl radical scavenger mannitol. In all the above respects, SIN-1 mimicked the production of hydroxyl radicals from the ascorbate-driven Fenton reaction. Catalase had no effect on the SIN-1 dependent generation of MDA, and superoxide dismutase was partially inhibitory. SIN-1 produces an oxidant with the properties of the hydroxyl radical by a mechanism clearly different to that of the Fenton reaction. We conclude that the simultaneous production of NO and superoxide from SIN-1 results in the formation of hydroxyl radicals. PMID- 1310596 TI - Effects of insulin and guanosine 5'-[gamma-thio]triphosphate on fatty acid synthesis and lipolysis within electropermeabilized fat-cells. AB - 1. Exposure to electric fields ('electroporation') has been used to investigate the mechanism of the action of insulin on the regulation of fatty acid synthesis and lipolysis in isolated rat fat-cells. 2. Exposure of the cells to electric fields (six pulses at 2 or 3 kV/cm) permitted the uptake of a number of low-Mr molecules normally excluded from cells, including sucrose (Mr 342), EDTA (Mr 394) and propidium iodide (Mr 668). At least 90% of the cells were found to be permeable to these species. 3. Insulin stimulated the synthesis of fatty acids in electroporated (2 kV/cm) cells to a similar extent (0.68 +/- 0.19 to 6.7 +/- 0.7 micrograms-atoms of glucose carbon/h per g, or 3.3 +/- 0.6 to 11.2 +/- 1.6 micrograms-atoms of H2O hydrogen/h per g) to that observed in non-electroporated cells. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]; 0.5 mM) also stimulated fatty acid synthesis (2-fold) and flux of glucose carbon into triacylglycerol glycerol (3-fold) in these cells, but had no effect on these parameters in non electroporated cells. 4. Lipolysis in the electroporated cells was stimulated by isoprenaline and also by GTP[S], but only the effects of isoprenaline were inhibited by insulin. 5. Exposure to a higher field strength (3 kV/cm) gave results qualitatively similar to those described above, although the effects of insulin and isoprenaline were diminished. 6. These studies provide evidence against a role for changes in Ca2+, and probably also Na+, K+ or Mg2+, in insulin action on fat-cells, but may support a role for GTP-binding proteins. PMID- 1310597 TI - Characterization of a novel inositol 1,4,5-trisphosphate receptor in isolated olfactory cilia. AB - Inositol 1,4,5-trisphosphate (InsP3), a product of G-protein-mediated receptor activation of phosphoinositide turnover, plays the role of a second messenger when olfactory neurons are stimulated with certain olfactory stimuli. In this paper we examine the specific binding of [3H]InsP3 to isolated olfactory cilia, microsomes and brain membranes from the channel catfish (Ictalurus punctatus) and, by photoaffinity labelling with an InsP3 analogue (125I-labelled 1-[3-(4 azidosalicyloxy)-aminopropyl]inositol 1,4,5-trisphosphate (125I-ASA-InsP3)], we tentatively identify the major InsP3-binding protein in catfish olfactory cilia. InsP3 binding to ciliary membranes is specific and saturable, with a Kd of 1.10 +/- 0.31 microM and a maximum number of binding sites (Bmax) of 17.6 +/- 5.8 pmol/mg. The rank order for potency of inhibition of [3H]InsP3 binding is Ins(1,4)P2 less than Ins(1,3,4)P3 less than Ins(1,3,4,5)P4 = Ins(1,4,5)P3 less than Ins(2,4,5)P3. Exposure of cilia membranes to u.v. light in the presence of 125I-ASA-InsP3 results in the labelling of a protein with apparent Mr 107,000. Labelling is specifically prevented by Ins(1,4,5)P3, Ins(2,4,5)P3 and Ins(1,3,4,5)P4, but not by Ins(1,4)P2 or Ins(1,3,4)P3. Both specific [3H]InsP3 binding and photoaffinity labelling of the Mr-107,000 protein were displaced by heparin. The Kd and the inhibition of [3H]InsP3 binding and of photoaffinity labelling by inositol phosphates and heparin are consistent with the ability of micromolar concentrations of Ins(1,4,5)P3 [but not Ins(1,3,4)P3] to activate the InsP3-gated currents in patch-clamp experiments with olfactory neurons. These results suggest that InsP3 binding to a Mr-107,000 cilia membrane protein may represent binding to the olfactory InsP3-gated cation channel. PMID- 1310598 TI - Characterization of 6-phosphofructo-2-kinase from foetal-rat liver. AB - Foetal and adult liver 6-phosphofructo-2-kinase (PFK-2) were purified by identical protocols. The native molecular masses of both enzymes were determined by gel filtration and were 89.1 and 100.0 kDa respectively. No differences were found in SDS/PAGE in 10%-acrylamide gel (55 kDa per subunit). The kinetic properties displayed by both enzymes were similar, except for the sensitivity to inhibition by sn-glycerol 3-phosphate. Foetal PFK-2 was a good substrate for phosphorylation by cyclic AMP-dependent protein kinase and protein kinase C, whereas the adult enzyme was phosphorylated only by cyclic AMP-dependent protein kinase. However, the phosphorylation affected only the kinetic properties of the adult enzyme, suggesting the presence in both enzymes of different sites of phosphorylation by cyclic AMP-dependent protein kinase. These differences in primary structure were consistent with the distinct chromatographic profiles of the phosphopeptides after digestion of the protein with CNBr. Western-blot analysis with antibodies specific for the N-terminal region of the liver-type PFK 2 poorly recognized the foetal enzyme, suggesting that both enzymes differ at least in the N-terminal sequence. PMID- 1310599 TI - Mastoparan promotes exocytosis and increases intracellular cyclic AMP in human platelets. Evidence for the existence of a Ge-like mechanism of secretion. AB - Recent studies have shown that mastoparan, an amphiphilic peptide derived from wasp venom, accelerates guanine nucleotide exchange and GTPase activity of purified GTP-binding proteins. In the present study we have examined the functional consequences of exposure of intact human platelets to mastoparan. Mastoparan promoted rapid (less than or equal to 1 min) dose-dependent increases in 5-hydroxy[14C]tryptamine and beta-thromboglobulin release from dense-granule and alpha-granule populations respectively. The exocytotic response did not result from a lytic effect of mastoparan and occurred in the complete absence of platelet shape change and aggregation. Liberation of [3H]arachidonate and increases in cytosolic [Ca2+] (detected with fura 2) were not observed in platelets stimulated with mastoparan. Similarly, in platelets preloaded with [3H]inositol during reversible electroporation, mastoparan did not cause the accumulation of [3H]inositol phosphates. Mastoparan-induced secretion was unaffected by preincubation with either the protein kinase C inhibitor staurosporine (10 nM-10 microM) or prostacyclin (PGI2; 100 ng/ml) and was not accompanied by phosphorylation of the 45 kDa protein kinase C substrate or the 20 kDa protein normally associated with platelet activation. The G-protein inhibitor guanosine 5'-[beta-thio]diphosphate (GDP[S]; 1 mM) attenuated the secretion induced by mastoparan in both intact and saponin-permeabilized platelets. Encapsulation of GDP[S] during reversible permeabilization inhibited mastoparan induced secretion, providing evidence for an intracellular action of GDP[S]. In all these studies thrombin (0.05-0.2 unit/ml) elicited characteristic responses, and thrombin-induced secretion was inhibited by staurosporine, PGI2 and GDP[S]. Mastoparan also increased intra-platelet cyclic AMP in a dose-dependent manner. Mastoparan and PGI2 increased 32P incorporation into a protein of approx. 24 kDa, whereas phosphorylation of a 50 kDa substrate was only seen in PGI2-stimulated platelets. These results indicate that mastoparan promotes secretion by a mechanism which does not involve stimulation of phospholipase C and suggest that the secretory event may result either from a direct fusogenic action of mastoparan and/or from stimulation of the putative exocytosis-linked G-protein, Ge. PMID- 1310600 TI - Optimal association-saturation procedure for estimating association and dissociation rate parameters in receptor studies. Application to solubilized A1 adenosine receptors. AB - A method of obtaining estimates of the maximum binding and association and dissociation rate constants for a receptor-ligand interaction is described. This new procedure, the association-saturation method, is based on an exact mathematical equation which defines the model without simplifications. The method proposed is readily applicable to any system consisting of one ligand and one receptor. With only four determinations, each involving one ligand concentration and an association time, it is possible to determine the number of specific binding sites, the dissociation and association rate constants and the equilibrium dissociation constant with accuracy. No dissociation curve is required, and only one point of the association curve for each ligand concentration is necessary. In addition to the higher confidence in the estimates of the parameter values obtained, this method leads to important savings in radiolabelled compounds and experimental time. The results were compared with those obtained with standard association-dissociation curves and saturation isotherms. The optimum number of replicates of each experimental point to obtain reliable estimates of different parameters is discussed on the basis of simulation studies. The performance of the procedure is analysed by means of association-saturation experiments with the agonist [adenine-2,8-3H,ethyl-2-3H]N6 phenylisopropyladenosine and solubilized A1 adenosine receptors from pig brain cortex. PMID- 1310602 TI - Beneficial effect of indapamide in experimental myocardial ischemia. AB - Indapamide, a nonthiazide chlorosulfamoyl diuretic, which possesses well-known antihypertensive properties, is able to scavenge free radical intermediates involved in lipid peroxidation. In this respect, it has almost the same level of action as alpha-tocopherol. Using an isolated working rat heart preparation, we investigated the effect of indapamide on the myocardial resistance to global total normothermic ischemia followed by reperfusion. The heart, isolated at the end of chronic oral pretreatment (7 day at 3 mg/kg body weight/day), was submitted to ischemia for 15 min and then reperfused. The main results were as follows: in the indapamide-treated group, 1) postischemic recovery of cardiac function was significantly better as compared to the untreated control group; 2) lactate dehydrogenase (LDH) release measured after 15 min of reperfusion was significantly reduced; 3) the myocardial content of organic hydroperoxides (HPO), taken as an index of lipid peroxidation, was significantly lowered, whereas the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) remained unchanged; and 4) electron spin resonance (ESR) analysis of coronary effluents, collected during the first minutes of reperfusion in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), revealed a significant modification in the treated group. These findings suggest that indapamide treatment is able to afford some protective effect to cardiac tissue during the early stage of postischemic reperfusion, and that this effect might be related to the antioxidant properties of inadapamide. PMID- 1310601 TI - A comparative study of endothelin- and platelet-activating-factor-mediated signal transduction and prostaglandin synthesis in rat Kupffer cells. AB - Endothelin-3 (ET-3) stimulated phosphoinositide metabolism and synthesis of prostaglandins in cultured rat Kupffer cells. ET-3-induced hydrolysis of phosphoinositides was characterized by the production of various inositol phosphates and of glycerophosphoinositol. The mechanism of ET-3-stimulated metabolism of phosphoinositides and synthesis of prostaglandins appeared to be distinct from the effect of platelet-activating factor (PAF) on these processes described previously [Gandhi, Hanahan & Olson (1990) J. Biol. Chem. 265, 18234 18241]. On a molar basis ET-3 was significantly more potent than PAF in stimulating phosphoinositide metabolism, e.g. ET-3-induced hydrolysis of phosphoinositides occurred at 1 pM, whereas PAF was ineffective at concentrations less than 1 nM. Upon challenging Kupffer cells with both ET-3 and PAF, an additive stimulation of phosphoinositide metabolism was observed, suggesting that the actions of these factors may be exerted on separate phosphoinositide pools. Treatment of Kupffer cells with pertussis toxin resulted in an inhibition of ET-3 induced phospholipase C activation; in contrast, cholera toxin treatment caused potentiation of ET-3-stimulated phospholipase C activity. Both toxins, however, inhibited PAF-stimulated phospholipase C activity. The present results suggest that the stimulatory effects of ET-3 and PAF on the phosphodiesteric metabolism of phosphoinositides in Kupffer cells require different guanine-nucleotide binding proteins. Furthermore, the effects of bacterial toxins on ET-3- and PAF induced phosphoinositide metabolism were not mediated by cyclic AMP. ET-3-induced metabolism of phosphoinositides was inhibited completely in Kupffer cells pretreated with ET-3, suggesting homologous ligand-induced desensitization of the ET-3 receptors. In contrast, similar experiments using PAF showed only a partial desensitization of subsequent PAF-induced phosphoinositide metabolism. In contrast to the increased production of prostaglandins E2 and D2 observed upon stimulation of Kupffer cells with PAF, ET-3 stimulated the biosynthesis of prostaglandin E2 only. Consistent with their additive effects on phosphoinositide metabolism, PAF and ET-3 exhibited an additive stimulation of the synthesis of prostaglandin E2. PMID- 1310603 TI - Effect of cyclophosphamide, total body irradiation, and zidovudine on retrovirus proliferation and disease progression in murine AIDS. AB - Murine acquired immunodeficiency syndrome (MAIDS) develops when C57B1/6 mice are inoculated with LP-BM5 murine leukemia viruses. Disease progression in these animals is characterized by lymphadenopathy, polyclonal B-cell activation, severe immunodeficiency, and death. Mice with MAIDS have been used to examine the efficacy of antiretroviral therapies for possible use in AIDS patients. In the present work, MAIDS mice were employed to test the hypothesis that established retroviral infection might be cured by the combined use of a cytotoxic agent (cyclophosphamide) and total body irradiation--a regimen reported to have successfully cured HIV-1 infection in one AIDS patient. Results indicate that the ablation of retrovirus-infected lymphoid cells reduced but did not eliminate LP BM5 infection. Moreover, this regimen was no more effective at controlling virus proliferation or preventing the polyclonal IgG activation characteristic of murine AIDS than was AZT alone. PMID- 1310604 TI - Propagation of SIV vectors by genetic complementation with a heterologous env gene. AB - In order to study SIV replication over a single round of replication virus particles were generated that contain a replication-defective vector containing a selectable marker. Genetic complementation between an env-deficient SIV variant and plasmid that expresses the env gene of an amphotropic murine retrovirus resulted in infectious SIV particles containing the vector. These pseudotyped particles exhibited an expanded host range through the use of an alternative receptor. This system should be useful in the genetic analysis of SIV nucleic acid replication. To determine whether the terminal cis acting components of the SIV genome might be sufficient for viral nucleic acid propagation a vector was generated which lack the internally located rev-responsive element. Propagation of this vector was reduced by at least 100-fold. PMID- 1310605 TI - Immunodeficiency and lymphoproliferative disease in an African green monkey dually infected with SIV and STLV-I. PMID- 1310606 TI - Evaluation of the actions and interactions of retinoic acid and epidermal growth factor on transformed urothelial cells in culture: implications for the use of retinoid therapy in the treatment of bladder cancer patients. AB - The effects and interactions were investigated of the two growth regulatory molecules alltrans retinoic acid (RA), and epidermal growth factor (EGF) on the in vitro expression by bladder cancer cell lines of the transformed phenotype (anchorage-independent growth in soft agar). When tested individually, the two molecules had opposite effects: RA (10(-11) to 10(-5) M) caused a dose-related reduction in anchorage-independent growth, whereas EGF (0.1 to 50 ng/ml) caused a dose-dependent increase. These effects were observed with both cell lines tested: RT112, a human papillary, non-metastatic bladder cancer cell line and RU-CL2, a rat metastatic bladder carcinoma cell line. When the effect of EGF (2.5 ng/ml) was tested against the growth inhibition produced by a range of doses of RA, EGF stimulated growth and reduced the degree of inhibition produced by RA at all dose levels. Conversely, a single dose of 10(-8) M RA tested against a range of EGF concentrations reduced the dose-related EGF-induced increase in anchorage independent growth. The two cell lines responded similarly to those combinations of RA and EGF in vitro, regardless of their different biological potentials in vivo. These experiments provide no evidence that RA potentiates EGF-induced growth, as has been observed by others using mesenchymal cells. RA could, therefore, theoretically be used to inhibit or delay bladder tumour recurrences. Trials would show whether oral doses of RA, or of synthetic retinoids metabolized to RA, would reach therapeutic levels and be chemopreventive in bladder cancer patients. PMID- 1310607 TI - Carcinoma of the male breast metastatic to the mandible. AB - A case is reported of male breast carcinoma which, among other bony sites, metastasized to the mandible. This case and the review of the literature illustrate the need to include the mandible in bone scans for metastatic disease in breast cancer. PMID- 1310608 TI - Kinetics of amide proton exchange in helical peptides of varying chain lengths. Interpretation by the Lifson-Roig equation. AB - The kinetics of amide proton exchange (1H----2H) have been measured by proton nuclear magnetic resonance spectroscopy for a set of helical peptides with the generic formula Ac-(AAKAA)m Y-NH2 and with chain lengths varying from 6 to 51 residues. The integrated intensity of the amide resonances has been measured as a function of time in 2H2O at pH* 2.50. Exchange kinetics for these peptides can be modeled by applying the Lifson-Roig treatment for the helix-to-coil transition. The Lifson-Roig equation is used to compute the probability that each residue is helical, as defined by its backbone (phi, psi) angles. A recursion formula then is used to find the probability that the backbone amide proton of each residue is hydrogen bonded. The peptide helix can be treated as a homopolymer, and direct exchange from the helix can be neglected. The expression for the exchange kinetics contains only three unknown parameters: the rate constant for exchange of a non-hydrogen-bonded (random coil) backbone amide proton and the nucleation (v2) and propagation (w) parameters of the Lifson-Roig theory. The fit of the exchange curves to these three parameters is very good, and the values for v2 and w agree with those derived from circular dichroism studies of the thermally induced unfolding of related peptides [Scholtz, J.M., Qian, H., York, E.J., Stewart, J.M., & Baldwin, R.L. (1991) Biopolymers (in press]). PMID- 1310609 TI - The method of time-resolved spin-probe oximetry: its application to oxygen consumption by cytochrome c oxidase. AB - This work broadens the scope and improves the time resolution of spin-probe oximetry, a technique in which small nitroxide spin probes detect oxygen consumption via change in their relaxation properties [Froncisz, W., Lai, C.-S., & Hyde, J. S. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 411-415]. For rapid oxygen kinetic studies we combined the methodology of spin-probe oximetry with a recently developed loop-gap resonator, stopped-flow EPR system [Hubbell, W. L., Froncisz, W., & Hyde, J. S. (1987) Rev. Sci. Instrum. 58, 1879-1886]. The technique used microliter volumes of reactant solutions. Enzymatic consumption of oxygen by cytochrome c oxidase in the presence of ferrocytochrome c substrate was followed continuously in time under limited-turnover conditions, where the concentration of oxygen consumed often was comparable to or less than the amount of enzyme present. In detecting less than micromolar oxygen concentration changes, we have achieved a time resolution of the order 30 ms when flow is stopped. Oxygen consumption was followed under two different limited-turnover conditions: In the first, the amount of oxygen consumed was limited by available ferrocytochrome c, and the time course of oxygen consumption and its pH dependence were compared with the optically detected ferrocytochrome c consumption. In the second, the oxygen consumed was ultimately limited by the availability of oxygen itself while ferrocytochrome c was regenerated and remained in excess.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310610 TI - Binding of verocytotoxin 1 to its receptor is influenced by differences in receptor fatty acid content. AB - Globotriaosylceramide [(Gal alpha 1-4Gal beta 1-4Glc-ceramide (Gb3)] was separated from human kidney, and the fatty acid composition was determined. Semisynthetic Gb3 molecular species of corresponding fatty acid chain length were prepared and compared for verotoxin (VT) binding affinity by TLC overlay, and a quantitative binding assay was performed in the presence of auxiliary lipids. Our results indicate that, within the natural range, fatty acid chain length has little effect on verotoxin binding but that Gb3 molecular species containing different fatty acids can interact to provide a higher affinity toxin receptor than any of the individual component receptor species. Receptor function as assayed by TLC overlay was not always found to correlate with binding in a lipid environment. Short-chain fatty acid Gb3 molecular species could not function as VT receptors under these conditions. Evidence is presented to suggest that fatty acid chain length can have a stereoselective effect on carbohydrate conformation. PMID- 1310611 TI - Proton exchange in DNA-luzopeptin and DNA-echinomycin bisintercalation complexes: rates and processes of base-pair opening. AB - Imino proton exchange studies are reported on the complexes formed by bisintercalation of luzopeptin around the two central A.T pairs of the d(CCCATGGG) and d(AGCATGCT) duplexes and of echinomycin around the two central C.G pairs of the d(AAACGTTT) and d(CCAAACGTTTGG) duplexes. The depsipeptide backbone of the drugs occupies the minor groove of the complexes at the bisintercalation site. The exchange time of the amide protons of the depsipeptide rings provides a lower estimate of the complex lifetime: 20 min at 15 degrees C for the echinomycin complexes and 4 days at 45 degrees C for the luzopeptin complexes. The exchange time of imino protons is always shorter than the complex lifetime. Hence, base pairs open even within the complexed oligomers. For the two base pairs sandwiched between the aromatic rings of the drug, the base-pair lifetime is strongly increased, and the dissociation constant is correspondingly reduced. Hence, the lifetime of the open state is unchanged. This suggests similar open states in the free duplex and in the complex. In contrast to the sandwiched base pairs, the base pairs flanking the intercalation site are not stabilized in the complex. Thus, the action of the bisintercalating drug may be compared to a vise clamping the inner base pairs. Analysis suggests that base pair opening may require prior unwinding or bending of the DNA duplex. PMID- 1310612 TI - Apparent oxygen-dependent inhibition by superoxide dismutase of the quinoprotein methanol dehydrogenase. AB - Methanol dehydrogenase activity, when assayed with phenazine ethosulfate (PES) as an electron acceptor, was inhibited by superoxide dismutase (SOD) and by Mn2+ only under aerobic conditions. Catalase, formate, and other divalent cations did not inhibit the enzyme. The enzyme also exhibited significantly higher levels of activity when assayed with PES under anaerobic conditions relative to aerobic conditions. The oxygen- and superoxide-dependent effects on methanol dehydrogenase were not observed when either Wurster's Blue or cytochrome c-55li was used as an electron acceptor. Another quinoprotein, methylamine dehydrogenase, which possesses tryptophan tryptophylquinone (TTQ) rather than pyrroloquinoline quinone (PQQ) as a prosthetic group, was not inhibited by SOD or Mn2+ when assayed with PES as an electron acceptor. Spectroscopic analysis of methanol dehydrogenase provided no evidence for any oxygen- or superoxide dependent changes in the redox state of the enzyme-bound PQQ cofactor of methanol dehydrogenase. To explain these data, a model is presented in which this cofactor reacts reversibly with oxygen and superoxide, and in which oxygen is able to compete with PES as an electron acceptor for the reduced species. PMID- 1310613 TI - Nucleosome spacing is compressed in active chromatin domains of chick erythroid cells. AB - We have cleaved the chromatin of embryonic and adult chicken erythroid cells using a novel nuclease that is capable of resolving clearly the nucleosomes of active chromatin. We found that in active chromatin, nucleosomes are spaced up to 40 base pairs closer together than in inactive chromatin. This was true for both "housekeeping" and "luxury" genes and was observed whether the digestion was carried out on isolated nuclei in vitro or by activating the endogenous nuclease in vivo. The close spacing extended several kilobases into flanking chromatin, indicating that this is a domain property of active chromatin, not just a characteristic of regions disrupted by transcription. A simple interpretation of our results is that the nucleosomes of active chromatin are mobile in vivo and, not being constrained by linker histones, freely move closer together. PMID- 1310614 TI - A water-lipid interface induces a highly dynamic folded state in apocytochrome c and cytochrome c, which may represent a common folding intermediate. AB - In this study, we have used CD and NMR techniques to investigate the secondary structure of (apo-) cytochrome c both in solution and when associated with micelles. In aqueous solution, the holoprotein cytochrome c is tightly folded at secondary and tertiary levels and differs strongly from its random-coiled precursor. However, in the presence of 12-PN/12-Pglycol (9:1) micelles, we observed a remarkable resemblance between the CD spectra of these partially helical proteins. The water-lipid interface induces a secondary folding of apocytochrome c, whereas cytochrome c is suggested to partially lose its tertiary structure. The exchange of all amide protons and, using deuterium-labeled proteins, of all amide deuterons with the solvent was monitored by NMR. A rapid exchange rate was observed, indicating that these folding states are highly dynamic. Saturation-transfer NMR of micelle-associated apocytochrome c showed that the exchange takes place at the (sub-) second time scale. The holoprotein in the presence of micelles was found to have two distinct exchange rates: (1) a fast rate, comparable to that found for the micelle-associated precursor and 4.5 times slower than that of the random-coiled apocytochrome c, and (2) a slow rate which is 75 times slower than the precursor in solution. Urea denaturation studies showed the micelle-bound proteins to have a low helix stability, which explains the inability of the lipid-induced secondary structure to prevent its labile protons from rapid exchange. The uniqueness of this lipid-induced highly dynamic folding state of (apo-) cytochrome c is demonstrated by comparison with amphiphilic polypeptides like melittin, and its implications for membrane translocation and functioning are discussed. PMID- 1310615 TI - Higher-order complex formation between the 72-kilodalton type IV collagenase and tissue inhibitor of metalloproteinases-2. AB - The collagenases are a class of matrix degradative enzymes whose actions are important in physiological and pathological processes. The human 72-kDa type IV collagenase (matrix metalloproteinase-2) and its proteinase inhibitor, tissue inhibitor of metalloproteinases-2 (TIMP-2), are produced as a proenzyme-inhibitor complex by numerous cell lines. We analyzed the quaternary structure of and enzyme-inhibitor interactions in the native enzyme-inhibitor complex by studying the pattern of complexes demonstrated by molecular weight determination in nondenaturing polyacrylamide gels and evaluating the products formed by reaction of the native complexes with cross-linking agents. Electrophoresis in native polyacrylamide gels demonstrates that approximately 79% of the latent enzyme is present in a 1:1 bimolecular complex with the inhibitor TIMP-2, with 21% present as a complete tetrameric complex of two molecules of collagenase combined with two molecules of TIMP-2. The enzyme complex activated with organomercurials displays a shift to a higher proportion of the bimolecular complex with only 5% present as higher molecular weight complexes. Cross-linking of the latent and active forms of the complex with bis(sulfosuccinimidyl) suberate (BS3) and bis(sulfosuccinimidyl) tartarate demonstrates both the 1:1 and 2:2 complexes as well as an intermediate form that appears to be a complex composed of two molecules of collagenase and one of TIMP-2. The distribution of cross-linked products is unchanged with the addition of excess TIMP-2 to the reaction mix, implying that the binding sites for TIMP-2 to the initial enzyme-inhibitor complex are all occupied when the stoichiometry is 1 to 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310616 TI - Anionic phospholipids are essential for alpha-helix formation of the signal peptide of prePhoE upon interaction with phospholipid vesicles. AB - The conformational consequences of the interaction of the PhoE signal peptide with bilayers of different types of phospholipids was investigated using circular dichroism. It was found that interaction of the signal peptide with anionic phospholipid vesicles of dioleoylphosphatidylglycerol and dioleoylphosphatidylserine results in induction of high amounts of alpha-helical structure of 70% and 57%, respectively. Upon addition of the signal peptide to cardiolipin vesicles, less but still significant alpha-helical structure was induced (29%). In contrast, no alpha-helix formation was observed upon the interaction of the signal peptide with zwitterionic dioleoylphosphatidylcholine vesicles. In bilayers of dioleoylphosphatidylcholine with dioleoylphosphatidylglycerol, it was shown that in the presence of 100 mM NaCl a minimum amount of 50% of negatively charged lipid was required for induction of the maximal percentage of alpha-helix, whereas in the absence of salt a minimum amount of 35% of negatively charged lipid was necessary. Induction of alpha-helix structure appeared to be correlated with functionality, since, in a less functional analogue of the PhoE signal peptide, the PhoE-[Asp-19,20] signal peptide, less alpha-helix was induced than in the wild-type PhoE signal peptide. It is proposed that the interaction with anionic phospholipids is essential for a functional conformation of the PhoE signal sequence during protein translocation. PMID- 1310617 TI - Structural basis for the low affinities of yeast cAMP-dependent and mammalian cGMP-dependent protein kinases for protein kinase inhibitor peptides. AB - Affinities of the catalytic subunit (C1) of Saccharomyces cerevisiae cAMP dependent protein kinase and of mammalian cGMP-dependent protein kinase were determined for the protein kinase inhibitor (PKI) peptide PKI(6-22)amide and seven analogues. These analogues contained structural alterations in the N terminal alpha-helix, the C-terminal pseudosubstrate portion, or the central connecting region of the PKI peptide. In all cases, the PKI peptides were appreciably less active as inhibitors of yeast C1 than of mammalian C alpha subunit. Ki values ranged from 5- to 290-fold higher for the yeast enzyme than for its mammalian counterpart. Consistent with these results, yeast C1 exhibited a higher Km for the peptide substrate Kemptide. All of the PKI peptides were even less active against the mammalian cGMP-dependent protein kinase than toward yeast cAMP-dependent protein kinase, and Kemptide was a poorer substrate for the former enzyme. Alignment of amino acid sequences of these homologous protein kinases around residues in the active site of mammalian C alpha subunit known to interact with determinants in the PKI peptide [Knighton, D. R., Zheng, J., Ten Eyck, L. F., Xuong, N-h, Taylor, S. S., & Sowadski, J. M. (1991) Science 253, 414-420] provides a structural basis for the inherently lower affinities of yeast C1 and cGMP-dependent protein kinase for binding peptide inhibitors and substrates. Both yeast cAMP-dependent and mammalian cGMP-dependent protein kinases are missing two of the three acidic residues that interact with arginine-18 in the pseudosubstrate portion of PKI. Further, the cGMP-dependent protein kinase appears to completely lack the hydrophobic/aromatic pocket that recognizes the important phenylalanine-10 residue in the N-terminus of the PKI peptide, and binding of the inhibitor by the yeast protein kinase at this site appears to be partially compromised. PMID- 1310619 TI - The endothelial cell binding determinant of human factor IX resides in the gamma carboxyglutamic acid domain. AB - The blood coagulation factor IX(a) binds specifically to a site on endothelial cells with a Kd of 2.0-3.0 nM. A number of previous studies have attempted to define the region(s) of factor IX(a) that mediate this interaction. These studies suggested that there are two regions of factor IX(a), the gamma-carboxyglutamic acid (Gla) domain and the epidermal growth factor like (EGF-like) domains, that mediate high-affinity binding to endothelial cells. Recently, however, the participation of the EGF1 domain has been excluded from the interaction. This indicated that if there was an EGF component of factor IX contributing to the binding affinity, then it must be in the second EGF-like domain. In order to further evaluate this relationship, we performed competitive binding experiments between 125I plasma factor IX and a set of six chimeric proteins composed of portions of factor VII and factor IX. Our data suggest that the high-affinity interaction between factor IX and the endothelial cell binding site is mediated by the factor IX Gla domain and that the factor IX EGF domains are not involved in binding specificity. PMID- 1310618 TI - Modulators of the glucocorticoid receptor also regulate mineralocorticoid receptor function. AB - Modulators are proposed to be novel ether aminophosphoglycerides that stabilize unoccupied and occupied glucocorticoid receptor steroid binding and inhibit glucocorticoid receptor complex activation. Two isoforms, modulator 1 and modulator 2, have been purified from rat liver cytosol [Bodine, P.V., & Litwack, G. (1990) J. Biol. Chem. 265, 9544-9554]. Since the mineralocorticoid receptor is relatively resistant to activation, modulator's effect on rat distal colon mineralocorticoid receptor function was examined. Warming of unoccupied receptor decreased residual specific [3H]aldosterone binding by 86 +/- 2%. Both modulator isoforms completely prevented this destabilization with Km's of 2 +/- 1 microM modulator 1 and 24 +/- 5 microM modulator 2. Warming of occupied mineralocorticoid receptors decreased [3H]aldosterone binding by 56 +/- 3%. Modulator only partially stabilized occupied receptor binding with Km's of 10 +/- 2 microM modulator 1 and 68 +/- 8 microM modulator 2. Modulator inhibited receptor activation with Km's of 3 +/- 1 microM modulator 1 and 33 +/- 10 microM modulator 2. Double-reciprocal analysis showed linear kinetics, and mixing modulator isoforms together had additive effects on unoccupied and occupied receptor steroid binding stabilization and activation inhibition. Colon cytosol contained a low molecular weight, heat-stable factor(s) which inhibited receptor activation and stabilized occupied receptor steroid binding. Molybdate completely stabilized unoccupied mineralocorticoid receptor steroid binding and inhibited activation with half-maximal effects at 3-4 mM but only stabilized occupied receptor binding by approximately 40%. These data indicate that (i) apparent physiologic concentrations of modulator stabilize mineralocorticoid receptor steroid binding and inhibit receptor activation, (ii) an aldosterone-responsive tissue contains a modulator-like activity, and (iii) molybdate mimics the effects of modulator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310620 TI - cGMP phosphodiesterase dependent light-induced scattering changes in suspensions of retinal disc membranes. AB - Light-induced GTP-dependent scattering changes are studied in suspensions of retinal disc membranes to which one or both of the purified proteins involved in the phototransduction mechanism (G-protein and cGMP phosphodiesterase) are reassociated; a scattering change which depends on the presence of both G-protein (G) and inhibited cGMP phosphodiesterase (PDE) and on an ATPase-dependent process, previously described in Bennett [(1986) Eur. J. Biochem. 157, 487-495] is compared to the signal observed in the absence of PDE or of ATP and to PDE activity. The same signal can also be induced either in the dark or in the light by addition of preactivated G in the presence of inhibited PDE. This PDE dependent scattering change is composed of two components (fast and slow); the variation of the amplitude and kinetics of both components with PDE or G concentration is similar to the variation of the active PDE state with two activator GGTP molecules (G with GTP bound), calculated with dissociation constants previously reported for the interaction between GGTP and PDE [Bennett, N., & Clerc, A. (1989) Biochemistry 28, 7418-7424]. The two components are therefore proposed to be associated with processes which depend on the formation of the active PDE state with two activators. PMID- 1310622 TI - Protein phosphorylation in regulation of photosynthesis. PMID- 1310623 TI - Charge anisotropy across biological membranes: evidence and implications. AB - Membrane proteins exhibit charge anisotropy across the bilayer with the vector positive inwards. The proton pumps, primary or secondary, which have been examined as a subset of these membrane proteins, also reveal charge anisotropy based on their sequence data. The direction of the anisotropy appears to satisfy the observed directional gradient of protons mediated by these proteins. A correct description of transport requires attention to local as well as field effects of the charge anisotropy of membrane proteins. PMID- 1310621 TI - Inhibition of protein kinase C by annexin V. AB - Annexin V is a protein of unknown biological function that undergoes Ca(2+) dependent binding to phospholipids located on the cytosolic face of the plasma membrane. Preliminary results presented herein suggest that a biological function of annexin V is the inhibition of protein kinase C (PKC). In vitro assays showed that annexin V was a specific high-affinity inhibitor of PKC-mediated phosphorylation of annexin I and myosin light chain kinase substrates, with half maximal inhibition occurring at approximately 0.4 microM. Annexin V did not inhibit epidermal growth factor receptor/kinase phosphorylation of annexin I or cAMP-dependent protein kinase phosphorylation of the Kemptide peptide substrate. Since annexin V purified from both human placenta and recombinant bacteria inhibited protein kinase C activity, it is not likely that the inhibitor activity was associated with a minor contaminant of the preparations. The following results indicated that the mechanism of inhibition did not involve annexin V sequestration of phospholipid that was required for protein kinase C activation: similar inhibition curves were observed as phospholipid concentration was varied from 0 to 800 micrograms/mL; the extent of inhibition was not significantly affected by the order of addition of phospholipid, substrate, or PKC, and the core domain of annexin I was not a high-affinity inhibitor of PKC even though it had similar Ca2+ and phospholipid binding properties as annexin V. These data indirectly indicate that inhibition occurred by direct interaction between annexin V and PKC. Since the concentration of annexin V in many cell types exceeds the amounts required to achieve PKC inhibition in vitro, it is possible that annexin V inhibits PKC in a biologically significant manner in intact cells. PMID- 1310624 TI - Reduction of CuA induces a conformational change in cytochrome c oxidase from Paracoccus denitrificans. AB - Cytochrome c oxidase (cytochrome aa3) from Paracoccus denitrificans contains a tightly bound manganese(II) ion, which responds to reduction of the enzyme by a change in its EPR signal (Seelig et al. (1981) Biochim. Biophys. Acta 636, 162 167). In this paper, the nature of this phenomenon is studied and the bound manganese is used as a reporter group to monitor a redox-linked conformational change in the protein. A reductive titration of the cyanide-inhibited enzyme shows that the change in the manganese EPR signal is associated with reduction of CuA. The change appears to reflect a rearrangement in the rhombic octahedral coordination environment of the central Mn2+ atom and is indicative of a redox linked conformational transition in the enzyme. The manganese is likely to reside at the interface of subunits I and II, near the periplasmic side of the membrane. One of its ligands may be provided by the transmembrane segment X of subunit I, which has been suggested to contribute ligands to cytochrome a and CuB as well. Another manganese ligand is a water oxygen, as indicated by broadening of the manganese EPR signal in the presence of H2(17)O. PMID- 1310625 TI - Role of insulin and IGF1 receptors in proliferation of cultured renal proximal tubule cells. AB - We have used a murine proximal tubule cell line (MCT cells) to determine the presence and binding characteristics of insulin and IGF1 receptors and to correlate these parameters with the concentration-response relationships for ligand-induced cellular proliferation. Separate insulin and IGF1 receptors were identified by equilibrium binding assays. Half-maximal displacement of either peptide occurred at 3-10 nM; crossover binding to the alternate receptor occurred with a 10- to 100-fold lower affinity. Peptide effects on cellular proliferation were determined by measuring [3H]thymidine incorporation. Both insulin and IGF1 stimulate thymidine incorporation in a dose-dependent manner with similar increases above the basal level. The estimated half-maximal stimulation (EC50) occurred at 4 nM for IGF1 and 8 nM for insulin. A comparison of the receptor binding affinities with the dose-response relationships for [3H]thymidine incorporation reveals that each growth factor appears to be exerting its effect via binding to its own receptor. Therefore, in this cell line, physiologic concentrations of either insulin or IGF1 can modulate cellular growth. To our knowledge this is the first demonstration of a mitogenic effect which may be modulated by ligand binding to the insulin receptor in proximal tubule epithelia. PMID- 1310626 TI - Lithium treatment of affective disorders: effects of lithium on the inositol phospholipid and cyclic AMP signalling pathways. AB - The effects of lithium (Li+) on the adenylyl cyclase and inositol phospholipid receptor signalling pathways were compared directly in noradrenergic and carbachol stimulated rat brain cortical tissue slices. Li+ was a comparatively weak inhibitor of noradrenaline-stimulated cyclic AMP accumulation with an IC50 of approx. 20 mM. By contrast, half-maximal effects of Li+ on inositol monophosphate (InsP) accumulation in [3H]inositol labelled tissue slices occurred at about 1 mM. A similar IC50 for Li+ of about 1 mM was also obtained for noradrenaline-stimulated accumulation of CMP-phosphatidate (CMPPA), a sensitive indicator of intracellular inositol depletion, in tissue slices that had been prelabelled with [3H]cytidine. The effect of myo-inositol (inositol) depletion on the prolonged activity of phosphoinositidase C (PIC) was examined in carbachol stimulated cortical slices using a novel mass assay for InsP. Exposure to a maximal dose of carbachol for 30 min in the presence of 5 mM Li+ caused a 10-fold increase in the level of radioactivity associated with the InsP fraction, but only a 2-fold increase in InsP mass. During prolonged incubations in the presence of both carbachol and Li+ the accumulation of InsP mass was enhanced if 30 mM inositol was included in the medium. The results are compatible with the inositol depletion hypothesis of Li+ action but do not support the concept that adenylyl cyclase or guanine nucleotide dependent proteins represent therapeutically relevant targets of this drug. PMID- 1310627 TI - Interleukin-1 inhibits PGE2 binding to macrophage-like P388D1 cells by a cyclic AMP-independent process. AB - The interaction between interleukin IL-1 alpha and PGE2 on P388D1 cells has been investigated. Preincubation of murine macrophage-like cells, P388D1, with IL-1 alpha (0-73 pM) reduced the binding of PGE2 to these cells in a concentration dependent manner. Scatchard analysis showed that IL-1 alpha decreased the PGE2 binding by lowering both the high and low affinity receptor binding capacities (from 0.31 +/- 0.02 to 0.12 +/- 0.01 fmol/10(6) cells for the high affinity receptor binding sites and from 2.41 +/- 0.12 to 1.51 +/- 0.21 fmol/10(6) cells for the low affinity receptor binding sites). However, the dissociation constants of the receptors of the IL-1 alpha-treated cells remained unchanged. Inhibition of PGE2 binding by IL-1 alpha did not involve changes in either protein phosphorylation or intracellular cyclic AMP levels. Our data clearly show that IL 1 alpha inhibits the binding of PGE2 to monocytes/macrophages and may thereby counter the immunosuppressive actions of PGE2. PMID- 1310628 TI - Comparison of influenza A virus and formyl-methionyl-leucyl-phenylalanine activation of the human neutrophil. AB - Influenza A virus (IAV) activates the human neutrophil, but induces a dysfunctional state as well. Cell activation may contribute to the containment of the virus and/or cause local tissue damage. Certain features of the neutrophil activation response elicited by IAV are distinctive when compared with that triggered by formyl-methyl-leucyl-phenylalanine (FMLP). An atypical respiratory burst response occurs in which hydrogen peroxide, but no superoxide, is formed. This unusual respiratory burst stoichiometry persists despite marked priming of the IAV-induced response. A comprehensive examination of the activation cascade initiated by these stimuli failed to show an explanation for these differences. Both IAV and FMLP comparably stimulate inositol trisphosphate and phosphatidic acid production. The subsequent increase in intracellular calcium (Ca2+i) upon FMLP stimulation was more dependent on extracellular Ca2+ than with IAV activation, but both stimuli induced Ca2+ influx. FMLP and IAV exhibited equal susceptibility to inhibition by protein kinase inhibitors in eliciting the respiratory burst, and actin polymerization occurred in response to each agonist. A possible explanation for the anomalous respiratory burst induced by IAV is that O2- is generated at an intracellular site inaccessible to assay, and/or virus binding to sialic acid constituents of the plasma membrane alters the O2- generating capacity of the respiratory burst oxidase; evidence for each mechanism is offered. PMID- 1310629 TI - Cytomegalovirus, HIV and peripheral neuropathies. PMID- 1310630 TI - Inhibitory role of gamma-amino-butyric acid in the rabbit urinary bladder. AB - Gamma-amino-butyric acid (GABA) is an established inhibitory neurotransmitter in the central nervous system (CNS) and it has also been identified in the bladder. We have investigated in the rabbit the effect of GABA on detrusor activity. Rabbit detrusor muscle strips were made to contract by electrical stimulation of their autonomic nerves or by the addition of carbachol. The addition of GABA caused substantial inhibition of muscle contraction. GABA acts on 2 classes of receptors-GABAA and GABAB. The inhibition was mediated via the GABAB receptors as its effect was mimicked by baclofen (a GABAB agonist) and inhibited by 2 hydroxysaclofen (a GABAB receptor antagonist). Inhibition was not prevented by bicuculline (a GABAA receptor antagonist). This inhibition may be due to a direct muscle effect since the inhibition, which occurred with carbachol-induced contraction, was not abolished by the addition of tetrodotoxin. GABA, acting via the GABAB receptor, produces substantial inhibition of muscle contraction in the rabbit urinary bladder. This raises the possibility of using GABAB analogues in the treatment of detrusor instability. PMID- 1310631 TI - Koilocytosis in neoplasia of the urinary bladder. AB - Koilocytosis is commonly regarded as indicative of human papilloma virus infection in the uterine cervix. In 1987 morphologically similar changes were reported in bladder tumours. This is confirmed in the present study, the incidence here being 65%. In addition the incidence of koilocytic change was shown here to increase from non-infiltrative WHO grade I to infiltrative WHO II lesions, and to be more common in bladder lesions in women with cervical koilocytosis. The latter is in keeping with our previous report that the incidence of koilocytosis in the cervix of patients with bladder neoplasia is higher than expected in the general population, adding support to the hypothesis that both lesions may be virus-related. PMID- 1310632 TI - Biliary bile acid profiles in familial adenomatous polyposis. PMID- 1310633 TI - Morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis. PMID- 1310634 TI - Emergency laparotomy in patients with AIDS. PMID- 1310635 TI - Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. AB - Carcinoid tumors are slowly growing neuroendocrine neoplasms which often present pronounced fibrosis around the tumor cells. We have previously shown by immunohistochemistry that carcinoid tumors express platelet-derived growth factor (PDGF) beta-receptors on surrounding stromal cells. In this report, 22 midgut carcinoids and 5 endocrine pancreatic tumors were examined for the presence of PDGF with a monoclonal antibody raised against a peptide corresponding to a part of the B-chain of PDGF which reacts strongly with the B-chain and weakly with the A-chain. They were also examined for PDGF alpha-receptors with an affinity purified polyclonal peptide antibody and for PDGF beta-receptor with the monoclonal antibody PDGFR-B2. PDGF was expressed on tumor cells and on adjacent stroma. PDGF alpha-receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas beta-receptors were seen only in the stroma. Tissue sections from some of these midgut carcinoids were also investigated by in situ hybridization for mRNA of PDGF A- and B-chains as well as alpha- and beta receptors. By in situ hybridization, abundant expression of mRNA for PDGF beta receptor and PDGF A-chain was observed in stromal cells adjacent to carcinoid tumor cell clusters, but the mRNA expression in the tumor cells themselves was at a low level. A few clustered tumor cells and stromal cells expressed mRNA for the PDGF alpha-receptor, thus consolidating the immunohistochemical findings. mRNA for the PDGF B-chain was detected in both tumor cells and stroma, but only at low levels. Our data suggest that PDGF is involved in the growth stimulation of the carcinoid tumor cells in an autocrine fashion and in the stimulation of stromal cell growth through paracrine and possibly autocrine mechanisms. Moreover, remarkably strong immunostaining of PDGF and the PDGF alpha-receptor was seen on peripheral nerve fibers. PMID- 1310636 TI - Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. AB - A principal difference between malignant and normal cells is the aberrant expression of oncogenes. Previously, we have reported on the expression of the insulin-like growth factor 1 receptor (IGF-1-R) in 93% of the human primary breast cancers studied. In the present study, we observed an increased gene copy number of the IGF-1-R in only 19 (2%) of 975 cases studied. The gene copy number of tumors with an amplified IGF-1-R gene varies between 3 and 56 (median, 24 copies). In 11 breast tumor samples with high (greater than or equal to 20 copies) IGF-1-R gene copy numbers, an additional amplification of either the c myc gene (n = 3) or int-2/bcl-1 genes (n = 5) was observed, whereas no amplification of the HER2/neu gene was detected. The c-fes gene (like the IGF-1-R gene located on chromosome 15q25-qter), was found coamplified with the IGF-1-R in two cases, in one case to the same high extent (38 gene copies, each) and in the other case to only a moderate extent (4 copies of the c-fes gene and 21 copies of the IGF-1-R gene). Tumors with an amplified IGF-1-R gene showed a noticeable increased expression of the IGF-1-R as measured by ligand binding assays on membrane preparations. The median amount of the IGF-1-R protein of the amplified tumors was observed to be 35 times higher when compared to nonamplified tumors (P less than 0.001). Patients with tumors containing a high (greater than or equal to 20 copies) IGF-1-R gene copy number tend to have a shorter median overall survival (42 months; range, 14-120+; n = 8) than patients with tumors having a low amplified (3-10 copies) IGF-1-R gene copy number (median, 77 months; range, 19.5-98+; n = 4). PMID- 1310637 TI - Low frequency of p53 gene mutation in tumors induced by aflatoxin B1 in nonhuman primates. AB - Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas from southern Africa and Qidong in China. To test this hypothesis, nine tumors induced by aflatoxin B1 in nonhuman primates were analyzed for mutations in the p53 gene. These included four hepatocellular carcinomas, two cholangiocarcinomas, a spindle cell carcinoma of the bile duct, a hemangioendothelial sarcoma of the liver, and an osteogenic sarcoma of the tibia. None of the tumors showed changes at the third position of codon 249 by cleavage analysis of the HaeIII enzyme site at codon 249. A point mutation was identified in one hepatocellular carcinoma at the second position of codon 175 (G to T transversion) by sequencing analysis of the four conserved domains (II to V) in the p53 gene. These data suggest that mutations in the p53 gene are not necessary in aflatoxin B1 induced hepatocarcinogenesis in nonhuman primates. The occurrence of mutation in codon 249 of the p53 gene in selective samples of human hepatocellular cancers may indicate involvement of environmental carcinogens other than aflatoxin B1 or that hepatitis B virus-related hepatitis is a prerequisite for aflatoxin B1 induction of G to T transversion in codon 249. PMID- 1310638 TI - Therapeutic advantage of high-affinity anticarcinoma radioimmunoconjugates. AB - The effect of the relative affinity (Ka) on the antitumor efficacy of monoclonal antibodies (MAbs) has been questioned. It has previously been shown in experimental models that the use of MAbs with higher relative Kas manifests itself in a higher percentage of injected dose of MAb bound to tumor. On the other hand, mathematical models have proposed that the use of higher affinity MAbs may be disadvantageous for antitumor effects, since higher Ka MAbs would bind more antigen and prevent penetration of MAb through tumor. To test this hypothesis, three MAbs reacting to the human pancarcinoma antigen TAG-72 were used as radioimmunoconjugates for therapeutic efficacy versus the LS-174T human colon carcinoma xenograft. MAbs B72.3, CC49, and CC83 have all been shown by depletion studies to react to the same molecule and to all react with overlapping epitopes. While the relative Ka of B72.3 is 2.5 x 10(9) M-1, the relative Kas of CC49 and CC83 are 16.2 and 27.7 x 10(9) M-1, respectively. Each MAb was radiolabeled with 131I, and each radioimmunoconjugate was assayed at five dose levels for therapeutic efficacy using the human xenograft model. The results of these studies demonstrate substantial therapeutic advantage of the higher affinity MAbs CC49 and CC83 versus B72.3 at every dose level. While 500 microCi of B72.3 were required to reduce tumor growth in only a minority of tumor-bearing animals, the use of the same amount or less of the radioimmunoconjugates of CC49 or CC83 resulted in strong antitumor effects in 80 to 100% of tumor-bearing animals. Thus, stronger antitumor effects were seen using as little as 2.5- to 3 fold less of the higher Ka immunoconjugates CC49 and CC83 as compared with B72.3. While we acknowledge the potential disadvantages of higher Ka MAbs in some situations, at least the experimental studies and model system described here show that a distinct therapeutic advantage exists with the use of higher affinity immunoconjugates. PMID- 1310639 TI - Mutagenic specificity of oxygen radicals produced by human leukemia cells. AB - An important source of endogenous oxygen radicals are phagocytic cells such as neutrophils and macrophages. The human leukemia cell line HL-60 can be induced to differentiate into a neutrophil-like cell population. Among the properties of these differentiated cells is the ability to produce reactive oxygen species when stimulated by tumor promoters. Mutagenesis induced by HL-60-generated free radicals was assessed using the M13mp2 forward mutation assay. Single-stranded M13mp2 DNA was coincubated with phorbol ester-stimulated HL-60 cells, after which mutations were scored by transfecting the DNA into SOS-induced Escherichia coli. The mutation frequency was increased 6-fold above background in DNA incubated with HL-60 cells. The majority of the mutations were single-base substitutions. However, approximately 6% of the mutations were tandem double substitutions that occurred in runs of adjacent cytidines. Overall, the mutations were clustered at apparent "hot spots," many of which were similar to sites seen using iron to generate oxygen radicals. These results suggest that human cells able to produce oxygen radicals in response to tumor promoters might play a significant role in the generation of tumors. PMID- 1310640 TI - Characterization of functional receptors for gastrointestinal hormones on human colon cancer cells. AB - Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function is not investigated. In the present study, 10 recently characterized human colon cancer cell lines were studied to determine whether they possess receptors for any of 12 different gastrointestinal hormones or neurotransmitters and to determine whether these receptors mediate changes in cellular function. Each of the cell lines exhibited receptors for at least one radioligand. Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, beta-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%. Analysis of [3H]N-methylscopolamine binding revealed a Kd of 0.2 nM for N-methylscopolamine with a binding capacity of 2500 sites/cell. With the agonist carbamylcholine, the receptor exhibited 2 classes of binding sites: one of high affinity (Kd 55 microM) representing 75% of the binding sites and one of low affinity (Kd 0.3 mM) representing 25% of the binding sites. Analysis of 125I-[Tyr4]bombesin binding revealed a receptor of high affinity (Kd 2.1 microM) with a binding capacity of 3300 sites/cell. Inhibition of binding by agonists revealed relative potencies of 125I-[Tyr4]bombesin greater than GRP much greater than neuromedin B, and two recently described antagonists were similar in potency to GRP. Analysis of 125I-VIP binding revealed a receptor having 2 classes of binding sites: one of high affinity (Kd 3.6 nM) and one of low affinity (Kd 1.7 microM) which represented the majority of the 5.5 x 10(6) binding sites/cell. The relative potencies of agonists were VIP greater than helodermin greater than peptide histidine methionine greater than secretin. Evaluation of biological activity mediated by the muscarinic cholinergic and bombesin receptors revealed an increase of intracellular calcium and of inositol triphosphate by specific receptor agonists. The presence or absence of receptors detected by binding correlated closely with the ability of selective receptor agonists to alter cell function. These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, beta-adrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1310641 TI - The synthetic hepatic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibit growth of MH1C1 rat hepatoma cells transplanted into Buffalo rats or athymic mice. AB - Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH1C1 rat hepatoma cells by 50-70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tumor growth in athymic mice. The amide free peptide pyroglutamylglutamylglycylserylaspartic acid which inhibited the tumor growth in all the models showed a curvilinear dose-response relationship with a maximal effect at 1000 pmol/animal in mice and at 100 pmol/animal in rats. The amidated peptide pyroglutamylglutamylglycylserylasparagine, which was only tested in the lung model, showed growth inhibition with 2, 20, or 200 pmol/animal, but 200 pmol/animal was most effective. We have recently reported that these peptides show cochromatography with hepatic growth inhibitory peptides, isolated from mouse liver. PMID- 1310642 TI - Suppression of tumorigenicity and anchorage-independent growth of BK virus transformed mouse cells by human chromosome 11. AB - Viral transformation models may be useful for detecting and mapping human tumor suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent cells but is unable to transform human cells, suggesting that oncosuppressive functions expressed in human cells control BKV oncogenic activity. We have transferred human chromosome 11 to BKV-transformed mouse cells. All of the cell clones were suppressed in the tumorigenic phenotype and anchorage-independent growth, except one clone which was nontumorigenic but maintained the ability to grow in soft agar. Cytogenetic analysis and DNA hybridization with chromosome 11 specific probes showed that all the reverted hybrids had an intact human chromosome 11, except the clone growing in semisolid medium which had lost the short arm. The results suggest that a gene located on 11p controls anchorage independence, whereas a gene on 11q controls the tumorigenicity of BKV transformed cells. BKV T-antigen was expressed in all the hybrid clones at the same level as in the parental cell line, indicating that the putative human tumor suppressor gene(s) do not inhibit expression of the viral oncogene and must operate by another mechanism in inducing reversion of the oncogenic phenotype. Since BKV-transformed mouse cells are highly susceptible to retrovirus infection, this model can be used for searching and cloning tumor suppressor gene(s) by retrovirus-mediated "insertional mutagenesis". PMID- 1310643 TI - Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. AB - We have examined the expression of 2 type IV collagen degrading enzymes (Mr 72,000 and 92,000 type IV collagenases) in human skin cancer by in situ hybridization. In all cases of infiltrating carcinomas of squamous cell (9 of 9) and basal cell (5 of 5) types, messenger RNA for the Mr 72,000 type IV collagenase was present in numerous fibroblasts. These were especially abundant in the stroma adjacent to the invasive tumor nodules. Malignant cells were negative for mRNA for the Mr 72,000 enzyme in all cases as were all other epithelial as well as endothelial cells. mRNA for the Mr 92,000 type IV collagenase was present in all 9 squamous cell and in 3 of the 5 basal cell carcinomas. In all these cases, a subpopulation of tissue macrophages was found to be positive, while malignant cells showed a signal for Mr 92,000 type IV collagenase in 6 of the squamous cell carcinomas but in none of the basal cell carcinomas. In all cases, the signal for this mRNA was confined to cells located at the tumoral/stromal interface or in the close vicinity of tumor nodules. No mRNA for any of the 2 collagenases was detected in 3 biopsies of normal skin. In vitro studies have indicated that collagenases are involved in the degradation of the extracellular matrix during cancer invasion. The present findings are consistent with such a role of the Mr 72,000 and 92,000 type IV collagenases in squamous and basal cell carcinomas in situ. The findings also demonstrate that degradative enzymes are not necessarily produced by the malignant cells themselves but may be generated by induction or recruitment of nonmalignant stromal cells. PMID- 1310644 TI - Case report: arachnoiditis following intracranial 'Thorotrast'. AB - A patient is reported with a painless, progressive cauda equina lesion due to arachnoiditis, the result of the contrast medium 'Thorotrast' (thorium dioxide) introduced into the brain over 30 years previously. Contrast medium introduced into the lumbar spine can give rise to aseptic adhesive inflammation (arachnoiditis). It rarely gives rise to clinical problems but, when it does so, is usually associated with back pain and only very rarely with progressive neurological deficit. PMID- 1310645 TI - Effect of soya and cellulose fibers on postprandial glycemic response in type II diabetic patients. AB - OBJECTIVE: We studied the effect on serum glucose and insulin of a preprandial ingestion of 7 g of soya fibers or of an equal amount of purified cellulose on eight non-insulin-dependent (type II) diabetic patients. RESEARCH DESIGN AND METHODS: Four tests were conducted in each patient in random order. In the first study, soya or cellulose was ingested before a standard breakfast, and postprandial glucose and insulin curves were determined. In the second study, intestinal absorption was investigated by means of a standard D-xylose absorption excretion test after the ingestion of soya or cellulose. RESULTS: Insulin profiles did not differ between the two treatments. The glycemic profiles after soya ingestion were lower than those after cellulose ingestion. The area under the glucose curve and glucose peaks were significantly higher after cellulose ingestion (area under the curve 20.2 +/- 3.88 vs. 15.57 +/- 4.42 mM x min, P = .05; glucose peaks 4.97 +/- 0.76 vs. 3.77 +/- 0.77 mM, P less than 0.02). The xylose tests were in the normal range, indicating that there was no interference with exose absorption, and no statistical difference was found between cellulose and soya treatment. CONCLUSIONS: It is concluded that soya fiber compared with purified cellulose has a favorable effect on the rise of postprandial glycemia in type II diabetic patients; moreover, the use of soya fibers did not carry any untoward side effect. PMID- 1310646 TI - Recurrence after breast ablation for ductal carcinoma in situ. AB - Three patients are described having locally recurrent invasive breast cancer after breast ablation for ductal carcinoma in situ (DCIS). All had initially extensive type ductal carcinoma in situ without evidence of invasion in adequately sampled microscopical studies. One patient developed a scar recurrence and lung metastases 2 years after surgery; one patient showed a scar recurrence 3 years after operation and one patient had a recurrence in the chest wall 27 years after surgery. Although generally stated that ablative therapy offers a 100% cure in case of DCIS, these cases illustrate that local recurrence may occur. Possible causes and preventions are discussed. PMID- 1310647 TI - Radiotherapy for unresectable endocrine pancreatic carcinomas. AB - Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or alpha-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas. PMID- 1310649 TI - Hydroxyapatite-coated implants. PMID- 1310648 TI - Calcium phosphate coatings for dental implants. Current status and future potential. AB - The initial experience with high-quality HA coatings has been positive. The application of HA coatings to metallic substrate implants represents the first time that the body can be directed as to where, and to some extent how, it should respond to their implantation, representing a truly incremental increase from metals material technology and an interim step towards more tailorable, biologically active systems. It remains clear at this writing that all HA coatings are not created equal and it remains an environment of "buyer beware." There is cause for optimism as new advances in the three essential criteria will only improve the current success rate. These advances and increases in efficacy will, as always, be pioneered in the dental and oral surgical disciplines. PMID- 1310650 TI - The surgical management of osseous defects associated with endosteal hydroxyapatite-coated and titanium dental implants. AB - As more and more patients choose implant therapies it will be incumbent upon the dentists placing, restoring, and maintaining endosseous implants to be armed with the most current information. There is a need for further research to answer the many significant questions in the management of osseous defects associated with dental implants. Some of these questions include: Which grafting materials yield the greatest repair? If resorbable materials (for example, DFDB) are not replaced by bone, are residual defects and peri-implant tissues similar to those which existed prior to osseous grafting procedures? If so, perhaps the combination of a nonresorbable graft like HA with DFDB may yield the wound-healing potential of both materials; for example, osseoinduction by DFDB and the benefits of a radiographic marker and defect filler provided by HA. Can reintegration occur on previously pathologically exposed implant surfaces? Do biodegradable barriers yield significant GTR, and do they resorb predictably? Is complete detoxification of the infected HA-coated surface possible or necessary for regeneration to occur? Which chemotherapeutic modality detoxifies HA-coated surfaces best clinically and at the histologic level? Or should infected HA coatings be removed before attempting implant repair? Are regenerative techniques (for example, GTR) predictable enough to treatment plan for them when we know there will be residual osseous defects after placing fixtures in their most ideal prosthetic position? If so, what defect types resolve most predictably following surgical correction? Should barriers be used in conjunction with grafting when placing 2-stage blade implants to generate bone in the slot preparation coronal to the shoulder of the blade? It is evident from the growing popularity and acceptance of implant therapies that these and other questions will need to be answered to continue the evolution of the science of this discipline. This author would encourage practitioners to keep abreast of the current research and developments in this field as new techniques, materials, and therapies are in a constant state of flux. PMID- 1310651 TI - Retrospective analysis of hydroxyapatite development for oral implant applications. AB - Ceramic forms of calcium phosphate, particularly HA, have been investigated extensively and used for hard-tissue implant applications for the past 20 years. HA ceramics still remain the most biocompatible bone implant material known and possess the added feature of becoming strongly bonded to living bone through natural-appearing bonding mechanisms. A variety of new or improved bone and tooth implant products have been developed using HA ceramics and thus this system has lead to overall improvements in dental hard-tissue repair and replacement. Because of HA's weak mechanical profile and relatively high chemical reactivity, however, bone implant devices composed in whole or in part of HA ceramics will fall short of being ideal permanent implant devices. Nevertheless, the development of a more fundamental and complete understanding of HA's bone-bonding mechanism could pave the way for a generation of surgical metals with permanent bone-bonding sites incorporated on their surfaces. PMID- 1310652 TI - Hydroxyapatite-coated implants in maxillofacial prosthetics. AB - The use of implants provides a secure, comfortable, and emotionally satisfactory attachment of the patient to the prosthesis. It is anticipated that patients who are willing to undergo placement of implants would have a greater commitment to continued use of their prostheses. Clearly, there is a greater affinity between a patient and his or her prosthesis when the attachment is an intimate one. The use of implants, then, could reverse functional deficiencies and raise the quality of the patient's post-disease life. PMID- 1310653 TI - Improved integration potential for calcium-phosphate-coated implants after glow discharge and water-storage. AB - Laboratory and clinical data support the conclusion that Radio-Frequency-Glow Discharge-Treatment (RFGDT) of calcium-phosphate-coated implants can accelerate their functional integration with bone at host sites. In addition to the benefits of surface cleaning and activation associated with RFGDT, a period of water storage prior to implantation also seems to be beneficial in eluting easily solubilized alkaline calcium components. PMID- 1310654 TI - Postscript: hydroxyapatite-coated implants. PMID- 1310655 TI - Hydroxyapatite-coated total hip replacement. AB - Biologic attachment of load-bearing orthopedic implants has developed as a response to long-term problems associated with polymethylmethacrylate cement fixation. Although early clinical results of uncemented hip and knee implants have been encouraging, histologic studies of retrieved implants have shown a distinct lack of bone apposition and ingrowth. Hydroxyapatite (HA) coatings applied to metallic implant substrates have been shown to enhance biologic fixation. These results have led to the clinical investigation of the use of HA coated total hip replacements. PMID- 1310656 TI - Clinical results from the calcitite-coated press fit APR hip system. AB - Hydroxyapatite (HA)-coated APR Total Hip Replacement was found to be superior to a press-fit only control group in a randomized trial. This study confirms the importance of biologic fixation for durability of total hip replacement as compared with press-fit fixation only. PMID- 1310657 TI - Early clinical results with the hydroxyapatite-coated porous LSF Total Hip System. AB - The design of and early clinical results with the uncemented porous-coated LSF Anatomic and Midstem Total Hip Systems are described. In a Food and Drug Administration-approved program, a random selection method was used to determine which patients receive implants with a hydroxyapatite (HA) coating applied to the porous surface and which patients receive non-HA-coated implants. The early clinical results with the HA-coated systems appear superior to the non-HA-coated systems. A greater percentage of patients with HA systems have clinical scores in the excellent/good range, which is primarily a reflection of less prosthesis related pain. Radiographically, all components appear well fixed with evidence of bone ingrowth. The HA-coated systems have a decreased incidence of radiolucencies, particularly in proximal zones. PMID- 1310658 TI - Clinical results with the hydroxyapatite-coated Omnifit hip stem. AB - A 2-year follow-up from a prospective clinical trial investigation of the hydroxyapatite (HA)-coated Omnifit-HA Hip Stem is presented. Assessment of clinical and functional evaluation parameters demonstrates the excellent results obtained with the femoral stem. Radiographic observations indicate a complete lack of fibrous tissue in the HA-coated regions of the stem, thus promoting direct load transfer between the stem and bone. Comparison with published studies suggests that the clinical results obtained with the HA-coated Omnifit-HA Hip Stem compare favorably with the prior reports. PMID- 1310659 TI - Clinical and radiographic experience with a hydroxyapatite-coated titanium plasma sprayed porous implant. AB - Recent efforts to improve the interface between implant and bone have involved the use of bioactive materials, specifically hydroxyapatite (HA). HA coatings applied to implants have shown excellent clinical results at 2 years. There have been no radiolucent lines around the HA-coated implants. The long-term strength of the HA coating-substrate bone interface remains a concern as osseointegration of the HA appears to be a consistent phenomenon. This can lead potentially to an interruption between the substrate itself and the osseointegrated coating. PMID- 1310660 TI - Prospective review of integral implants. AB - There are several factors that strongly correlate to HA-coated implant success and the prevention of implant morbidity. Surgical placement must be performed without compromise in technique. Implants placed into thin ridges or those that had dehiscence of their surface did not uniformly gain bone attachment levels during the healing period. Countersinking implants in extraction sites was critical; labial bone implant defects should be grafted with particulate HA. HA grafts to labial bone defects at the time of implant placement surgery are still short-term. Primary closure of all implant surgical sites prevented epithelial invagination into the surgical site and is associated with improved bone height around implants. Premature exposure of the implant during the healing period is associated with crestal bone loss. Loading forces should be physiologic, with maintenance of a physiologic equilibrium by a balanced restoration. Bone bulk should be created or preserved. Bone around implants may adversely respond to excessive loading forces. In the posterior maxilla, crestal bone loss has been observed that seems to result from excessive cantilever-type forces placed on the implants or from when implants are placed in the posterior mandible developed progressive bone loss that was associated with several factors. These factors included articulation against a natural occlusion, a horizontal ridge contour level with the external oblique ridge, a nonhygienic restoration, and the lack of keratinized gingiva against the abutment. Whether titanium implants develop progressive bone loss in the face of these factors is unknown. The presence of keratinized gingiva strongly correlated to bone maintenance in the posterior mandible. Because of this statistically significant finding, implant exposure should preserve all keratinized gingiva by transposing it labially to the implants. Most patients who receive implants for dental restoration have lost teeth because of caries and periodontal disease. The patient's behavioural patterns need to be redirected to maintain excellent oral hygiene in order to prevent peri-implant gingivitis. A hygienic restoration may be one of the most important factors associated with excellent implant health. Immediately upon receiving their restoration, patients did well maintaining their peri-implant hygiene. However, many patients do not continue their peri-implant hygiene. However, many patients do not continue their new hygiene methods and need to be strongly reminded to maintain their oral hygiene. Some patients do better than others. For some, a porcelain restoration with the restoration subgingival is well tended, but for others 4 to 5 mm of space needs to be established in order to prevent gingival problems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1310661 TI - Long-term retrospective studies on hydroxyapatite coated endosteal and subperiosteal implants. AB - This article reports a long-term retrospective study on hydroxyapatite-coated implants, which covers more than 6 years of clinical use. The authors discuss not only cylinder implants, but blade and subperiosteal implants as well. This study reveals that, for the time covered, a definite clinical advantage exists to coating implants with hydroxyapatite. PMID- 1310662 TI - Status of the hydroxyapatite-coated unilateral subperiosteal implant using direct bone impressions. AB - The hydroxyapatite (HA)-coated unilateral subperiosteal implant is a highly predictable and successful implant system when specifically indicated. Osseous and soft-tissue adaptability and compatibility appear enhanced through the use of this HA-coated framework. Indications, techniques, common complications, and typical case studies are presented. HA coatings may provide the next generation of already proved successful subperiosteal implant systems. PMID- 1310663 TI - Long-term retrospective studies on the CT-scan, CAD/CAM, one-stage surgery hydroxyapatite-coated subperiosteal implants, including human functional retrievals. AB - The subperiosteal implant has long been regarded as the most successful, predictable, and versatile of all implant systems. In some cases, however, anatomic morphology and surgical technique present certain limitations for the subperiosteal procedure. Through CAD/CAM multiplanar diagnostic imaging, not only have we been able to eliminate the first stage of the surgical procedure, but we have expanded the capabilities and versatility of the subperiosteal procedure. In addition, coating the subperiosteal implant frame with hydroxyapatite has allowed the achievement of bony union, thus increasing the long-range prognosis of the individual case. PMID- 1310664 TI - Placement of hydroxyapatite-coated implants into fresh or recent extraction sites. AB - Factors important in the placement of HA-coated dental implants in fresh or recent extraction sites are case selection, treatment planning, and surgical modifications. The importance of good periodontal health and effective oral hygiene cannot be over-emphasized. Technique variations include careful extraction of the tooth or teeth, use of a surgical guide stent to overcome the "guidance" of the sockets, placement of the implants at least 1 mm apical to the socket edges, use of grafting materials to fill residual voids adjacent to the cylindrical implants, and special soft tissue closure techniques. Guided tissue regeneration methods are often used to enhance wound closure and improve bone regeneration around the implants. Clinical results suggest that HA-coated implants clinically integrate equally well in both fresh sockets and healed edentulous areas. Clinicians can comfortably consider placement of HA-coated dental implants in fresh extraction sockets for their patients and can anticipate favorable results with the application provided that the proper principles are followed. PMID- 1310665 TI - Association of U6 snRNA with the 5'-splice site region of pre-mRNA in the spliceosome. AB - U6 snRNA is one of the five RNA species required for splicing of nuclear pre mRNAs. High conservation of its sequence has led to the hypothesis that U6 snRNA plays a catalytic role in splicing. If this is the case, U6 snRNA should be localized close to sites where the splicing reaction occurs. However, this has never been demonstrated. Here, we have shown that U6 snRNA is cross-linked to the 5'-splice site region of pre-mRNA by UV irradiation during the in vitro splicing reaction. We have also detected the cross-link of U6 snRNA and the region around the branchpoint of the intron lariat. The results show that U6 snRNA is present near the splice sites in the splicing reaction and support the idea that U6 snRNA is a catalytic element in the spliceosome. PMID- 1310666 TI - Bacterial cytochromes c biogenesis. AB - We report the primary sequence analyses of two loci, hel and ccl, whose gene products are required specifically for the biogenesis of c-type cytochromes in the Gram-negative photosynthetic bacterium Rhodobacter capsulatus. Genetic and molecular analyses show that the hel locus contains at least four genes, helA, helB, helC, and orf52, and the ccl locus contains two genes, ccl1 and ccl2, that are essential for cytochromes c biogenesis. HelA is homologous to a class of proteins called ABC transporters and helA, helB, and helC are proposed to encode an export complex. Cytochrome c2-alkaline phosphatase gene fusions were used to show that apocytochrome c2 synthesis and secretion are not affected by the hel and ccl defects. Ccl1 and Ccl2 possess typical signal sequences to direct them to the periplasm. The periplasmic orientation of Ccl1 was confirmed using a Ccl1 alkaline phosphatase gene fusion. The Ccl1-alkaline phosphatase gene fusion analysis also demonstrated that Ccl1 does not require hel genes for its synthesis and secretion. Ccl1 is homologous to proteins encoded by chloroplast and mitochondrial genes, suggesting analogous functions in these organelles. Taken together, these results support the hypothesis that the hel-encoded proteins are required for the export of heme to the periplasm where it is subsequently ligated to the c-type apocytochromes. PMID- 1310667 TI - Yeast and human TFIIDs are interchangeable for the response to acidic transcriptional activators in vitro. AB - Previous work showed that human TFIID fails to support yeast cell growth, although it is nearly identical to yeast TFIID in a carboxy-terminal region of the molecule that suffices for basal, TATA-element-dependent transcription in vitro. These and other findings raised the possibility that TFIID participates in species-specific interactions, possibly with mediator factors, required for activated transcription. Here, we report that human TFIID and amino-terminally truncated derivatives of yeast TFIID are fully functional in support of both basal transcription and the response to acidic activator proteins in a yeast in vitro transcription system. Conversely, and in contrast to previously published results, yeast TFIID supports both basal and activated transcription in reactions reconstituted with human components. This functional interchangeability of yeast and human TFIIDs argues strongly against species specificity with regard to TFIID function in basal transcription and the response to acidic activator proteins. In addition, our results suggest that any intermediary factors between acidic activators and TFIID are conserved from yeast to man. PMID- 1310668 TI - Primary gastrointestinal malignant lymphomas associated with Epstein-Barr virus after heart transplantation. AB - Gastrointestinal involvement has been reported in 12-21% of post-transplant lymphoproliferative disorders but is unusual in the setting of heart transplantation. We report four post-transplant lymphoproliferative disorders observed among the 174 heart transplant recipients of our series, all of which were primary malignant lymphomas of and confined to the digestive tract. The mean onset time from transplantation was 22 months. Small intestine lesions were present in all four patients, with gastric involvement in one. Histologically, the tumour was monomorphic of immunoblastic type in one case and polymorphic in the three other cases. Analysis of cytoplasmic immunoglobulins demonstrated the presence of a major monoclonal subset in all patients. Epstein-Barr virus genome was found in numerous tumour cells by in situ hybridization. The exclusive localization to the digestive tract and the lymphoepithelial lesions observed in two cases suggest that these lymphoproliferations might originate from mucosa associated lymphoid tissue. PMID- 1310669 TI - The histology and immunohistochemistry of small cell mesothelioma. AB - The object of this study was to describe the histology and immunohistochemistry of 13 small cell mesotheliomas, concentrating on reliable distinctions between them and small cell carcinoma. All 13 tumours showed regions of more typical mesothelioma if multiple blocks were examined. No tumours showed the streams, ribbons, rosettes, or haematoxyphilic blood vessels that are typical of small cell carcinoma. Mitotic figures were relatively scarce and the nuclei had a particularly characteristic open appearance with prominent nucleoli and delicate chromatin. Nuclear moulding was not seen. No tumour produced neutral mucin. Immunohistochemical positivity for neuron-specific enolase (NSE) was found in 11/13, cytokeratin in 9/13 and Leu-7 in 4/13 but none was positive for chromogranin A, carcino-embryonic antigen (CEA) or leucocyte common antigen (LCA). We conclude that the accurate diagnosis of small cell mesothelioma is possible, provided that the clinical presentation is known, the tumour is adequately sampled and the microscopy carefully assessed. In small biopsy specimens, where the diagnosis is less straightforward, immunohistochemistry for CEA, and perhaps LCA and chromogranin A may be helpful. NSE and Leu-7 positivity is common in these tumours and might be misleading if interpreted as reliable evidence of neuroendocrine differentiation. PMID- 1310670 TI - Influence of outer membrane mutations on susceptibility of Escherichia coli to the dibasic macrolide azithromycin. AB - Azithromycin differs chemically from erythromycin by having an extra positive charge created by the presence of a methyl-substituted nitrogen in the 15 membered macrolide ring. This results in substantially increased potency against Gram-negative bacteria. Therefore, the possibility was considered that azithromycin was taken across the outer membrane of Escherichia coli by the self promoted uptake route, which is utilized by other cationic antibiotics including polymyxins and aminoglycosides. Azithromycin, like polymyxin B and gentamicin, demonstrated equal activity against porin-sufficient and porin-deficient E. coli strains but its MIC was increased eight-fold by magnesium supplementation. Nevertheless, an outer membrane-altered mutant DC2 was eight-fold more susceptible than its parent strain UB1005 to azithromycin, indicating that the outer membrane was a permeability barrier to this macrolide. A mutant SC9252 which had an alteration in the self-promoted uptake of polymyxin and gentamicin, was more resistant to azithromycin, polymyxin and gentamicin compared to its parent SC9251. Further azithromycin, like polymyxin B and gentamicin, was capable of weakly permeabilizing cells to the hydrophobic fluorophor 1-N-phenyl naphthylamine, a process antagonized by Mg2+. The monobasic macrolide erythromycin on the other hand was less affected by the SC9252 mutation, less effectively antagonized by Mg2+, and was a far less effective permeabilizer than dibasic azithromycin. These data are consistent with the hypothesis that the improved efficacy of azithromycin compared to erythromycin against E. coli reflects its better access to the self-promoted uptake pathway due to its additional positive charge. PMID- 1310671 TI - Detection of ciprofloxacin resistance in gram-negative bacteria due to alterations in gyrA. AB - Two plasmids containing the cloned Escherichia coli wild-type gyrA gene were used to transform ciprofloxacin-resistant Gram-negative clinical isolates to screen for DNA gyrase A-mediated quinolone resistance. The results show that the technique is simple and applicable to a wide range of Gram-negative species including E. coli, Enterobacter cloacae, Klebsiella aerogenes, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Campylobacter jejuni and Neisseria gonorrhoeae. The use of an arithmetical MIC series of dilutions (as opposed to standard geometrical ones) was found to be essential during screening for the detection of altered gyrase A. The observations were consistent with the suggestion that DNA gyrase is highly conserved among different species of bacteria and that gyrase A-mediated resistance can occur in all. PMID- 1310672 TI - What happens to nucleosomes during transcription? PMID- 1310673 TI - Induction of cyclin mRNA and cyclin-associated histone H1 kinase during liver regeneration. AB - Cyclins and cyclin-associated cdc kinases are key regulators of oocyte maturation (Maller, J. L. (1990) in The Biology and Medicine of Signal Transduction (Nishizuka, Y., Endo, M., and Tanaka, C., eds) pp. 323-328, Raven Press, New York), yeast cell cycles (Nurse, P. (1990) Nature 344, 503-508), DNA replication in cell-free systems (D'Urso, F., Marraccino, R. L., Marshak, R. R., and Roberts, J. M. (1990) Science 250, 786-791), and amphibian cell proliferative transitions (Hunt, T. (1991) Nature 350, 462-463). The extent to which these regulatory molecules participate in the growth control of differentiated epithelial cells like hepatocytes is unknown. Therefore, we investigated the expression of "G1" (E, C, and D) and "G2/M" (A, B1, and B2) cyclin mRNAs, the relative levels of cyclin A- and B1-associated histone H1-kinase activity, and the appearance of cyclin-associated kinases (p32/p33cdk2 and p33/p34cdc2) in regenerating rat liver and in control tissues from sham hepatectomized rats. To do this, we exploited a battery of human cyclin cDNAs and cyclin antisera that recognize rat molecules. The results suggest an apparent sequence of regeneration-specific changes: 1) elevated and induced expression of cyclins E (2.1 kilobases (kb)) and C (4 kb), and D mRNAs (4 kb), within 12 h, respectively; 2) induction of cyclins A (3.4 and 1.8 kb), B1 (2.5 and 1.8 kb), and B2 (1.9 kb) mRNAs at 24 h; 3) induction of cyclin A- and B1-associated nuclear histone H1 kinase at 24 h; and 4) enhanced levels of PSTAIRE-containing proteins of Mr approximately 32-33 and 33-34 kDa in nuclear extracts from 24-h regenerating liver that co-immunoprecipitate with cyclin A and B1 antisera, respectively. These observations provide an intellectual framework that unifies the biology of hepatocyte mitogenesis, proto oncogene expression, and the machinery of the cell cycle. PMID- 1310674 TI - The role of cytoplasmic deoxycytidine kinase in the mitochondrial effects of the anti-human immunodeficiency virus compound, 2',3'-dideoxycytidine. AB - 2',3'-Dideoxycytidine (ddC) is a potent inhibitor of human immunodeficiency virus replication in vitro and shows beneficial effects in AIDS therapy. The compound inhibits mitochondrial DNA (mtDNA) synthesis at a clinically relevant concentration, which could be responsible for the side effects of ddC observed in the clinic. Thymidine (dThd), one of the substrates of mitochondrial deoxypyrimidine kinase (dPyd kinase), was not able to reverse the mitochondrial toxicity of ddC in CEM cells. Furthermore, the cytoplasmic deoxycytidine kinase (dCyd kinase)-deficient CEM cells were highly resistant to the mitochondrial toxicity of ddC. These data suggest a critical role for cytoplasmic dCyd kinase in the mitochondrial toxicity of ddC. The metabolites of ddC, but not ddC itself, were able to inhibit mtDNA synthesis in isolated mitochondria. The potency of the inhibitory effect was in the order of ddCTP greater than ddCDP greater than ddCMP greater than ddC. The lack of inhibition by ddC of mtDNA synthesis could be due to the inefficient ddC phosphorylation in mitochondria. Although the mitochondrial dPyd kinase was reported to phosphorylate ddC, the phosphorylation of ddC in isolated mitochondria was not detectable. The data suggest that ddC is phosphorylated to ddCTP in the cytoplasm and then transported into mitochondria to exert its inhibitory effect on mtDNA synthesis. PMID- 1310675 TI - Glyconeogenesis from L-proline involves metabolite inhibition of the glucose-6 phosphatase system. AB - L-Proline's glycogenic action is unlike that of other amino acids in that it produces effects beyond those explainable by a simple increase in osmolarity (Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M., and Plomp, P. J. A. M. (1990) J. Biol. Chem. 265, 955-959). We postulate that this effect may relate to inhibition of hepatic glucose-6-P hydrolysis by a proline-derived metabolite. We tested this hypothesis with isolated livers from rats fasted 48 h which were perfused with L-proline or L-glutamine. Net glucose and net glycogen production and levels of glucose-6-P and certain other hepatic metabolites were measured. The data obtained support our hypothesis by demonstrating fundamental differences in the metabolic fates of proline and glutamine in the liver. Both pass through alpha-ketoglutarate in the initial stage of gluconeogenesis, but proline supports hepatic glycogen formation while glutamine does not. The concomitant increase in hepatic glucose-6-P and proline-associated glyconeogenesis suggests that inhibition of glucose-6-P hydrolysis by a proline-derived metabolite may divert glucose-6-P produced from proline from glucose production and to glycogen synthesis. This conclusion is supported by the effects of perfusions with and without proline (3-mercaptopicolinate present) on (a) glyconeogenesis and glucose formation from dihydroxyacetone, (b) net glucose uptake and glycogen formation with 30 mM glucose as substrate, and (c) glucose production from endogenous glycogen in perfused livers from fed rats. PMID- 1310676 TI - Uptake of cadmium is diminished in transfected mouse NIH/3T3 cells enriched for metallothionein. AB - To determine the relationship between cellular uptake of cadmium and content of metallothionein, we measured uptake of 109Cd in cells that differed in content of metallothionein (MT). MT cells were derived from NIH/3T3 cells by transfection with a plasmid containing the genome of bovine papilloma virus and the mouse metallothionein-I gene, driven by the promotor for the glucose-regulated protein of 78 kDa. Control cells were similarly transfected with bovine papilloma virus based plasmids with the gene for metallothionein inverted and thus separated from the promoter (TM), or deleted, along with the promoter (BPA). The number of copies of bovine papilloma virus-based plasmids was similar in MT, TM, and BPA cells, approximately 100 per cell. MT cells were more than 10 times more resistant to the lethal effect of cadmium than were the control cells. Synthesis of metallothionein was 15-fold greater in the MT cells than in the TM or BPA cells. The uptake of 109Cd by the cells enriched in metallothionein was 4-fold less than by the control cells. These data suggest that an increased content of metallothionein may protect some cells from the toxic effects of cadmium, in part, by diminishing uptake of the metal. PMID- 1310677 TI - A deletion in the extracellular domain of the alpha platelet-derived growth factor (PDGF) receptor differentially impairs PDGF-AA and PDGF-BB binding affinities. AB - 32D cells transfected with the human alpha platelet-derived growth factor receptor (alpha PDGFR) bind PDGF-AA, -AB, and -BB isoforms with high affinity, and the binding of each can be efficiently competed by all three isoforms. In an effort to develop better understanding of spatial relationships of binding sites for PDGF-AA and -BB, we constructed an alpha PDGFR mutant which deleted amino acids 150-189 within its extracellular domain. This mutant showed a marked decrease in high affinity binding sites for PDGF-AA without comparable alteration in affinity for PDGF-BB. These findings imply that the high affinity binding sites for PDGF-AA and PDGF-BB in the alpha PDGFR extracellular domain are not structurally coincident. PMID- 1310678 TI - Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell free system. AB - A rabbit reticulocyte lysate system that has been used to reconstitute functional complexes between steroid receptors and the 90-kDa heat shock protein (hsp90) has been used here to form complexes between the pp60src tyrosine kinase and hsp90. Reticulocyte lysate forms complexes between hsp90 and a temperature-sensitive mutant of Rous sarcoma virus pp60v-src, which is normally present in cytosol virtually entirely in the multiprotein complex form. In addition, hsp90 in the lysate complexes with wild-type pp60v-src, of which only a small portion is normally recovered in cytosol in the native multiprotein complex, and with the cellular homolog, pp60c-src, which has never been recovered in cytosol in the form of a native multiprotein complex with hsp90. Moreover, the reticulocyte lysate-reconstituted complex also contains the 50-kDa phosphoprotein component of the native pp60v-src multiprotein complex. The native and reconstituted pp60src hsp90 complexes have similar thermal stability and, like steroid receptor heterocomplexes, they are stabilized by molybdate. As previously shown with reticulocyte lysate-reconstituted steroid receptor heteroprotein complexes, the reconstituted pp60src multiprotein complex contains hsp70, which is a major candidate for providing the protein unfoldase activity required for hsp90 association. PMID- 1310679 TI - In vitro and in vivo regulation of thyrotropin receptor mRNA levels in dog and human thyroid cells. AB - Regulation of thyrotropin (TSH) receptor (TSHr) mRNA accumulation as compared with two other thyroid differentiation markers (thyroglobulin and thyroperoxidase (TPO] has been investigated by Northern blot. In dogs in vivo, chronic stimulation of the thyroid TSHr mRNA although it increased the levels of thyroglobulin and TPO mRNA. In dogs treated with thyroxin, the quiescent thyroids expressed normal levels of TSHr and TPO mRNA but depressed levels of thyroglobulin mRNA. In primary cultures of dog thyrocytes, dedifferentiation of the cells by treatment with epidermal growth factor or 12-O-tetradecanoylphorbol 13-acetate led to decreased TSHr mRNA levels and nearly abolished thyroglobulin and TPO gene expression. However, TSHr mRNA was always present, compatible with the fact that these cells, when treated by TSH, reexpress differentiation. Treatment of the cells with TSH or forskolin transiently increased the TSHr mRNA level after 20 h, an effect inhibited by cycloheximide. This up-regulation was confirmed at the protein level: forskolin-treated cells showed an enhanced cAMP response to TSH and an increased binding of labeled TSH to their membranes. Long term TSH treatment led to a slight down-regulation of TSHr mRNA in dog thyrocytes, but in human thyroid cells no marked down-regulation was observed. PMID- 1310680 TI - Structure function analysis of vitamin D analogs with C-ring modifications. AB - Analogs of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) with substitutions on C-11 were synthesized. Small apolar substitutions (11 alpha-methyl, 11 alpha fluoromethyl) did not markedly decrease the affinity for the vitamin D receptor, but larger (11 alpha-chloromethyl or 11 alpha- or 11 beta-phenyl) or more polar substitutions (11 alpha-hydroxymethyl, 11 alpha-(2-hydroxyethyl] decreased the affinity to less than 5% of that of 1 alpha,25-OH)2D3. Their affinity for the vitamin D-binding protein, however, increased up to 4-fold. The biological activity of 11 alpha-methyl-1 alpha,25-(OH)2D3 closely resembled that of the natural hormone on normal and leukemic cell proliferation and bone resorption, whereas its in vivo effect on calcium metabolism of the rachitic chick was about 50% of that of 1 alpha,25-(OH)2D3. The 11 beta-methyl analog had a greater than 10-fold lower activity. The differentiating effects of the other C-11 analogs on human promyeloid leukemia cells (HL-60) agreed well with their bone-resorbing activity and receptor affinity, but they demonstrated lower calcemic effects in vivo. Large or polar substitutions on C-11 of 1 alpha,25-(OH)2D3 thus impair the binding of the vitamin D receptor but increase the affinity to vitamin D-binding protein. The effects of many C-11-substituted 1 alpha,25-(OH)2D3 analogs on HL-60 cell differentiation exceeded their activity on calcium metabolism. PMID- 1310681 TI - Location of a Bombyx mori receptor binding region on a Bacillus thuringiensis delta-endotoxin. AB - Receptor binding studies were performed with 125I-labeled trypsin-activated insecticidal toxins, CryIA(a) and CryIA(c), from Bacillus thuringiensis on brush border membrane vesicles (BBMV) prepared from Bombyx mori larval midgut. Bioassays were performed by gently force feeding B. mori with diluted toxins. CryIA(a) toxin (LD50; 0.002 micrograms) was 200 times more active against B. mori larvae than CryIA(c) toxin (LD50; 0.421 micrograms) and showed high-affinity saturable binding. The Kd and the binding site concentration for CryIA(a) toxin were 3.5 nM and 7.95 pmol/mg, respectively. CryIA(c) toxin (Kd, 50.35 nM; Bmax, 2.85 pmol/mg) did not demonstrate high-affinity binding to B. mori BBMV. Control experiments with CryIA(a) and CryIA(c) toxins revealed no binding to mouse small intestine BBMV and nonspecific binding to pig kidney BBMV. These data provide evidence that binding to a specific receptor on the membrane of midgut epithelial cells is an important determinant with respect to differences in insecticidal spectrum of insecticidal crystal proteins. To locate a B. mori receptor binding region on the CryIA(a) toxin, homologous and heterologous competition binding studies were performed with a set of mutant proteins which had previously been used to define the B. mori "specificity domain" on this toxin (Ge, A. Z., Shivarova, N. I., and Dean, D. H. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4037 4041). These mutant proteins have had regions of their genes reciprocally exchanged with the cryIA(c) gene. A B. mori receptor binding region on CryIA(a) toxin includes the amino-terminal portion of the hypervariable region, amino acids 332-450, which is identical to the previously described B. mori specificity determining region. These data provide direct evidence that delta-endotoxins contain a tract of amino acids that comprise a binding region and as a results determines the specificity of a toxin. PMID- 1310682 TI - Mechanism of polyethylene glycol interaction with the molten globule folding intermediate of bovine carbonic anhydrase B. AB - Polyethylene glycol has been shown to bind to the molten globule intermediate on the bovine carbonic anhydrase B folding pathway. The mechanism of this interaction has been extensively probed. Polyethylene glycol (PEG) binds weakly to the molten globule first intermediate as measured by hydrophobic interaction chromatography, but PEG does not bind to either the native state or the second intermediate. The binding of PEG to the molten globule has been confirmed with both intrinsic fluorescence and fluorescence quenching experiments which indicate a single PEG-binding site on the molten globule. Electron paramagnetic resonance spectroscopic studies with nitroxide-labeled PEG also indicate a single binding site. Additional electron paramagnetic resonance studies with spin-labeled carbonic anhydrase B suggest that a conformational change occurs in the molten globule intermediate after PEG binds to the surface. The formation of a PEG molten globule complex results in a reduction in self-association of this compact hydrophobic structure. PEG-molten globule complex formation is analogous to the observed interaction between chaperonins and a molten globule intermediate (Martin, J., Langer, T., Boteva, R., Schramel, A., Horwich, A.L., and Hartl, F.U. (1991) Nature 352, 36-42). PMID- 1310683 TI - Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways. AB - Sphingosine kinase was partially purified and characterized from rat brain microsomes. A new assay, utilizing octyl-beta-D-glucopyranoside and sphingosine mixed micelles, was developed to quantitate formation of the sphingosine-1 phosphate product. The assay was proportional with respect to time and protein, displayed Michaelis-Menten kinetics, and was subject to surface dilution in regard to the sphingosine substrate. Investigations into substrate specificity showed that the enzyme is specific for the erythro-enantiomers of sphingosine and dihydrosphingosine. Neither of the threo-enantiomers were phosphorylated in this system, but both were found to be potent competitive inhibitors of sphingosine kinase activity. Human platelet sphingosine kinase activity displayed substrate and inhibitor specificities similar to the rat brain enzyme. A mixture of DL threo-dihydrosphingosine competitively inhibited sphingosine kinase activity in a dose dependent manner in isolated platelets. DL-Threo-dihydrosphingosine caused a prolongation of the inhibition of thrombin-induced protein kinase C-dependent 40 (47)-kDa protein phosphorylation in platelets. D-, L-, or DL-Threo dihydrosphingosine may be useful as a tool to investigate D-Erythrosphingosine metabolism and the function of sphingosine-1-phosphate in signal transduction processes. PMID- 1310684 TI - The v-sis oncogene product but not platelet-derived growth factor (PDGF) A homodimers activate PDGF alpha and beta receptors intracellularly and initiate cellular transformation. AB - The v-sis oncogene product p28v-sis and the platelet-derived growth factor (PDGF) B chain share 92% homology with each other and over 50% homology with the PDGF A chain. Exogenously added homodimers of PDGF A and PDGF B and of p28v-sis are potent mitogens but only PDGF B and p28v-sis induce transformation when endogenously expressed with a strong promoter. Because exogenous PDGF AA and PDGF BB both initiate a full mitogenic response, understanding the mechanisms underlying the difference in their transforming potential may clarify how growth factor genes act as oncogenes. In this work, we compared cells expressing high levels of PDGF A and v-sis. We observed that transformation by v-sis correlated directly with the rapid degradation (t1/2 approximately 20 min) of the alpha and beta PDGF receptors, with a failure of either the alpha or beta receptor to be fully processed and with the association of high levels of phosphatidylinositol (PI) 3-kinase with immunoprecipitates of the PDGF receptors. In contrast, in cells expressing essentially equal levels of PDGF A, transformation was not detected, alpha and beta PDGF receptor processing was normal, and association of PI 3-kinase with receptors in immunoprecipitates was not found above control values. The ability of v-sis to autoactivate PDGF receptors within processing compartments and to initiate activation of the PI 3-kinase signaling pathway coupled with the failure of PDGF A to activate its receptor intracellularly and to induce transformation when endogenously expressed at high levels suggests that the internal autoactivation of PDGF receptors may be essential for transformation by v-sis. PMID- 1310685 TI - Evidence for the formation of a functional complex between vasoactive intestinal peptide, its receptor, and Gs in lung membranes. AB - The molecular weight of the vasoactive intestinal peptide (VIP) receptor in rat lung and its interaction with the stimulatory guanine nucleotide-binding protein (Gs) were assessed by covalent cross-linking, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and immunological techniques. Studies with two cross-linking agents indicated that the VIP receptor in this tissue is a single polypeptide of Mr = 54,000. The VIP-occupied receptor could be cross linked to neighboring proteins after detergent solubilization; higher molecular weight complexes of Mr = 114,000 and 184,000 were formed. Immunoblotting with antisera against G-protein subunits demonstrated that both complexes contained the alpha-subunit of Gs as well as the 125I-VIP cross-linked receptor whereas only the Mr = 184,000 complex contained the beta-subunit. Pretreatment with GTP reduced the prominence of these complexes, verifying the functional nature of this receptor-Gs association. Studies with a third cross-linking agent, ethylene glycol bis(succinimidyl succinate), provided direct evidence of physically associated, ternary VIP-receptor-Gs complexes actually in the membrane milieu. That these complexes were functionally associated with shown by their inhibition by anti-Gs alpha anti-serum. Since treatment of membranes with guanosine 5'-O-(3 thiotriphosphate) resulted in the separation of the VIP-cross-linked receptor from Gs such that no cross-linking could occur, we conclude that the binding of GTP analogs induces a conformational change in Gs in the membrane milieu. PMID- 1310686 TI - Phosphatidylinositol-3-kinase in isolated rat adipocytes. Activation by insulin and subcellular distribution. AB - Insulin increases phosphatidylinositol-3-kinase (PI-3-kinase) activity in Chinese hamster ovary cells transfected with human insulin receptor (Ruderman, N. B., Kapeller, R., White, M. F., and Cantley, L. C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1411-1415). The subcellular distribution of PI-3-kinase has not been investigated, and it is unclear if insulin has a stimulatory effect on PI-3 kinase in a nonproliferating target tissue, and, if so, whether this effect is subject to counter-regulation. To address these questions, we studied the effect of insulin on PI-3-kinase activity in isolated rat adipocytes. Activity was measured in plasma membranes, intracellular membranes, and cytosol of control and insulin-treated adipocytes, and in anti-Tyr(P) immunoprecipitates prepared from these fractions and from whole cell lysates. Treatment of adipocytes with insulin (200 nM) caused a half-maximal increase in anti-Tyr(P)-immunoprecipitable PI-3 kinase activity in whole cell lysates within 2 min. This effect was concentration dependent, and it was sensitive to inhibition by norepinephrine. In insulin stimulated cells, 75% of anti-Tyr(P)-immunoprecipitable PI-3-kinase activity was found in the low density microsomes. This fraction also exhibited the highest specific activity of PI-3-kinase, and insulin caused a further increase in this activity. Anti-Tyr(P)-immunoprecipitable PI-3-kinase activity was also found in the plasma membranes of insulin-treated cells, but this accounted for only a minor portion of the total and anti-Tyr(P)-immunoprecipitable PI-3-kinase activity. The majority of PI-3-kinase activity (90%) in control cells was cytosolic, but this was not increased in response to insulin nor was it anti Tyr(P)-immunoprecipitable. These data demonstrate that insulin increases the activity of PI-3-kinase in adipocytes and this effect is subject to inhibition by a physiological antagonist of insulin action. The data also indicate that the effect of insulin to increase PI-3-kinase activity is expressed primarily in the low density intracellular membranes and to a lesser extent in the plasma membranes. PMID- 1310687 TI - Heparin selectively inhibits the transcription of tissue-type plasminogen activator in primate arterial smooth muscle cells during mitogenesis. AB - How heparin inhibits vascular smooth muscle cell proliferation and migration has not been established. We have investigated the hypothesis that heparin inhibits vascular smooth muscle cell proliferation and migration by interfering with the expression and activity of proteases such as plasminogen activators. In an in vitro mitogenesis model, tissue-type plasminogen activator (tPA) mRNA and protein increase in baboon smooth muscle cells stimulated with fetal bovine serum or phorbol esters. Heparin inhibits smooth muscle cell proliferation and suppresses the induction of tPA mRNA and protein while it has little effect on the mRNA of urokinase-type plasminogen activator, plasminogen activator inhibitor type I, and a number of genes that are also modulated by serum and phorbol esters. The inhibitory effect on tPA mRNA is specific to heparin-like molecules and does not depend on the anticoagulation activity of heparin. The increase in tPA mRNA is due to increased transcription, which is suppressed by heparin. The induction of tPA by serum and phorbol esters is diminished by protein kinase C inhibitors such as H7 or staurosporine and by protein kinase C depletion. Since heparin suppresses the induction of the tPA gene by phorbol esters, these results suggest that heparin may interfere with the protein kinase C pathway. PMID- 1310689 TI - Dealing with DCIS. PMID- 1310688 TI - Immunopurified 25-hydroxyvitamin D 1 alpha-hydroxylase and 1,25-dihydroxyvitamin D 24-hydroxylase are closely related but distinct enzymes. AB - The chick kidney mitochondrial cytochrome P-450 1,25-dihydroxyvitamin D3 24 hydroxylase was partially purified by sequential polyethylene glycol precipitation, aminohexyl-Sepharose 4B, and hydroxylapatite chromatography. The specific activity of the final preparation, when reconstituted with NADPH, adrenodoxin, and adrenodoxin reductase, was 245 pmol/min/mg of protein or 0.56 pmol/min/pmol of P-450. The specific cytochrome P-450 content was 0.45-0.73 nmol/mg of protein. BALB/c mice immunized with this preparation developed serum polyclonal antibodies to the 24-hydroxylase, as demonstrated by immunoprecipitation. Splenic lymphocytes from an immunized mouse were fused with myeloma NSI/1-Ag-4-1 cells, and hybridomas secreting monoclonal antibodies to the 24-hydroxylase were detected by immunoprecipitation. The hybridoma lines were cloned by limiting dilution and further characterized as IgG1, IgG3, and IgM subclasses. In one-dimensional immunoblots of soluble 24-hydroxylase preparations, the monoclonal antibodies revealed a single band with an apparent molecular weight of 59,000. The monoclonal antibodies did not cross-react with cytochrome P-450s from other species but immunoprecipitated and immunoblotted a soluble chick renal mitochondrial 25-hydroxyvitamin D3 1 alpha-hydroxylase preparation, demonstrating the close similarity of these two hydroxylases. These antibodies were coupled to Sepharose CL-4B and used to isolate to homogeneity the two enzymes from chick kidney mitochondria. Amino-terminal sequences and amino acid composition data demonstrate that these enzymes are different but homologous. PMID- 1310690 TI - New understanding of myositis. PMID- 1310691 TI - Characterization of a functional thrombin receptor. Issues and opportunities. PMID- 1310692 TI - Long-term activation of protein kinase c causes chronic Na/H antiporter stimulation in cultured proximal tubule cells. AB - To examine the role of protein kinase C as a chronic regulator of proximal tubule Na/H antiporter activity, the effect of phorbol 12-myristate 13-acetate (PMA) on the Na/H antiporter was studied in cultured proximal tubule cells. Short-term activation of protein kinase C by 5 min exposure to PMA caused an acute increase in Na/H antiporter activity that was not prevented by cycloheximide or actinomycin D and did not persist 24 h later. Long-term activation of protein kinase C by 2 h exposure to PMA caused a dose-dependent increase in Na/H antiporter activity 24 h later. This latter effect was due to protein kinase C activation in that it was inhibited by sphingosine and was not seen with 4 alpha PMA, an inactive analogue. The chronic effect of PMA was inhibited by 10 nM actinomycin D or 7 microM cycloheximide. Proximal tubule cells exposed to PMA for 2 h demonstrated a two- to threefold increase in Na/H antiporter mRNA (mRNANa/H) abundance 4 h later. In conclusion, short-term activation of protein kinase C leads to a transient increase in Na/H antiporter activity that is independent of transcription and translation, whereas long-term activation of protein kinase C causes a persistent increase in antiporter activity that is dependent on transcription and translation and is associated with increased mRNANa/H abundance. This latter effect may mediate increased Na/H antiporter activity in a number of chronic conditions. PMID- 1310693 TI - Isoprenoid metabolism is required for stimulation of the respiratory burst oxidase of HL-60 cells. AB - The formation of oxygen radicals by phagocytic cells occurs through the activation of a multiple-component NADPH oxidase system. An unidentified low molecular weight GTP-binding protein has been proposed to modulate the activity of the NADPH oxidase. The low molecular weight GTP-binding proteins undergo posttranslational processing, including an initial covalent incorporation of an isoprenyl group. To test whether such an isoprenylation reaction might be required for the activity of the oxidase, we utilized compactin and lovastatin as inhibitors of the isoprenylation pathway. Treatment of DMSO-differentiated HL-60 cells with compactin produced a concentration-dependent inhibition of O2- formation in response to FMLP or phorbol myristate acetate. Cell viability was not affected nor was normal differentiation of the HL-60 cells into a neutrophil like cell. The inhibitory effect of compactin was specifically prevented by addition of exogenous mevalonic acid to the HL-60 cells, indicating that the inhibitory effects of the drug were due to blockade of the pathway leading to isoprenoid synthesis. Addition of cholesterol, ubiquinone, or dolichol, which are also downstream products of the isoprenoid pathway, did not override the inhibitory effects of the drug. Subcellular fractions were prepared from compactin-treated cells, and the location of the compactin-sensitive factor was determined by complementation analysis in a cell-free NADPH oxidase system. The inhibited factor was localized to the HL-60 cytosol. These data suggest that an isoprenoid pathway intermediate is necessary for activation of the phagocyte NADPH oxidase. This is likely to represent the requirement for an isoprenoid moiety in the posttranslational modification of a low molecular weight GTP binding protein. Our studies provide support for the involvement of such a low molecular weight GTP-binding protein in NADPH oxidase activation. PMID- 1310694 TI - Role of a pituitary-specific transcription factor (pit-1/GHF-1) or a closely related protein in cAMP regulation of human thyrotropin-beta subunit gene expression. AB - cAMP regulation of the human thyrotropin-beta (TSH beta) gene cAMP was studied in two heterologous cell lines, a human embryonal kidney cell line (293) and a rat pituitary cell line (GH3). In 293 cells, human TSH beta gene expression was not stimulated by the adenylate cyclase activator forskolin or the cAMP analogue 8 bromo-cAMP (8-Br-cAMP). On the other hand, these agents induced human TSH beta gene expression 4-12-fold in GH3 cells. Deletion analysis demonstrated that the regions from +3 to +8 bp and from -128 to -61 bp were both necessary for cAMP stimulation. The latter region contains three DNA sequences homologous to a pituitary-specific transcription factor, Pit-1/GHF-1, DNA-binding site. Gel mobility assays demonstrated that a radiolabeled human TSH beta probe (-128 to 61 bp) formed five specific DNA-protein complexes with mouse thyrotropic tumor (MTT) nuclear extract and two specific complexes with in vitro translated Pit 1/GHF-1. Four of the five MTT complexes and both in vitro Pit-1/GHF-1 complexes were reduced or eliminated by excess of an unlabeled Pit-1/GHF-1 DNA-binding site from the rat growth hormone gene, but not a mutated version of the same DNA fragment, suggesting that Pit-1/GHF-1 or a closely related thyrotroph protein binds to these DNA sequences. In 293 cells, co-transfection of an expression vector containing the Pit-1/GHF-1 cDNA restored cAMP-responsiveness to the human TSH beta promoter (5.2- and 6.6-fold maximal stimulation by 8-Br-cAMP and forskolin, respectively) but not the herpes virus thymidine kinase promoter (1.2 fold maximal stimulation by either agent). Thus we conclude that the human TSH beta gene is positively regulated by cAMP in GH3 but not 293 cells. Since the human TSH beta gene contains at least one high-affinity binding site for Pit 1/GHF-1 in a region necessary for cAMP stimulation and cAMP stimulation could be restored to the human TSH beta promoter in a previously nonresponsive cell line by the addition of Pit-1/GHF-1, this suggests that Pit-1/GHF-1, or a closely related protein in the thyrotroph, may be a trans-acting factor for cAMP stimulation of the TSH beta gene. PMID- 1310695 TI - "Mirror image" antagonists of thrombin-induced platelet activation based on thrombin receptor structure. AB - Platelet activation by thrombin plays a critical role in hemostasis and thrombosis. Based on structure-activity studies of a cloned platelet thrombin receptor, we designed two "mirror image" antagonists of thrombin and thrombin receptor function. First, "uncleavable" peptides mimicking the receptor domain postulated to interact with thrombin were found to be potent thrombin inhibitors. Second, proteolytically inactive mutant thrombins designed to bind but not cleave the thrombin receptor were found to be specific antagonists of receptor activation by thrombin. The effectiveness of these designed antagonists in blocking thrombin-induced platelet activation suggests a model for thrombin receptor interaction and possible strategies for the development of novel antithrombotic agents. PMID- 1310697 TI - Prediction of relapse or survival after resection in human hepatomas by DNA flow cytometry. AB - To investigate the change of DNA content and the effect of synthetic phase (S phase) fraction on hepatocytes and hepatomas, DNA content and S-phase fraction were measured by flow cytometry in human livers and hepatoma tissues. The ploidy status of nontumor parts of resected hepatoma, fetal liver, and focal nodular hyperplasia were diploid, similar to that of the normal liver. Three patterns of DNA ploidy in human hepatoma cells were newly classified, namely, pattern I, diploid tumors; pattern II, aneuploid tumors with single G0/G1 peak; and pattern III, aneuploid tumors with more than one G0/G1 peaks. Among the 130 resectable hepatomas measured for DNA ploidy status, 84 (64.6%) were pattern I, 20 (15.4%) pattern II, and 26 (20%) pattern III. Multivariate analyses for those 130 patients who underwent hepatic resection showed that, in addition to tumor size, DNA ploidy was another prognostic factor in predicting overall survival and disease-free survival. Patients with small tumors (less than 5 cm) had a significantly higher overall survival rate than those with large tumor (greater than 5 cm). Patients with pattern III hepatomas had a significantly lower overall survival rate and a higher recurrent rate than did those with pattern I or pattern II tumors. The S-phase fraction was a significant predictor of overall survival rate in patients with pattern II, but not with pattern I, tumors. We conclude that DNA flow-cytometric measurements of ploidy and S-phase fraction are potential important prognostic predictors in patients with resectable hepatomas. PMID- 1310696 TI - Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor. AB - Recombinant human growth hormone (HuGH) and human prolactin (HuPRL), but not GH of bovine or porcine origin, prime human neutrophils for enhanced superoxide anion (O2-) secretion. Since HuGH, but not GH of other species, effectively binds to the HuPRL receptor (HuPRL-R), we used a group of HuGH variants created by site directed mutagenesis to identify the receptor on human neutrophils responsible for HuGH priming. A monoclonal antibody (MAb) directed against the HuPRL-R completely abrogated O2- secretion by neutrophils incubated with either HuGH or HuPRL, whereas a MAb to the HuGH-R had no effect. The HuGH variant K172A/F176A, which has reduced affinity for both the HuGH-binding protein (BP) and the HuPRL BP, was unable to prime human neutrophils. This indicates that priming is initiated by a ligand-receptor interaction, the affinity of which is near that defined for receptors for PRL and GH. Another HuGH variant, K168A/E174A, which has relatively low affinity for the HuPRL-BP but slightly increased affinity for the HuGH-BP, had much reduced ability to prime neutrophils. In contrast, HuGH variant E56D/R64M, which has a similar affinity as wild-type HuGH for the HuPRL BP but a lower affinity for the HuGH-BP, primed neutrophils as effectively as the wild-type HuGH. Finally, binding of HuGH to the HuPRL-BP but not to the HuGH-BP has been shown to be zinc dependent, and priming of neutrophils by HuGH was also responsive to zinc. Collectively, these data directly couple the binding of HuGH to the HuPRL-R with one aspect of functional activation of human target cells. PMID- 1310699 TI - Food sources of energy, macronutrients, cholesterol, and fiber in diets of women. AB - Data from the 1985 Continuing Survey of Food Intakes by individuals were used to calculate the contributions of individual foods to women's intakes of energy, protein, carbohydrate, fat, saturated fatty acids, cholesterol, and fiber. We separated nearly all food mixtures into their constituent ingredients, grouped the ingredients together with similar foods, and examined the contributions of those foods. Yeast breads that were neither whole grain nor higher fiber contributed about 7% of the energy to the diets, which made them the leading source of energy of the foods we examined. The leading sources of protein were animal products: poultry contributed approximately 12%, beef contributed about 19%, cheese contributed about 8%, and pork contributed about 6%. The various fats and oils were the greatest contributors to fat, and cheese was the chief source of saturated fatty acids. Eggs were the major source of cholesterol; they provided around 36% of the total. Two of the top three sources of carbohydrate- regular soft drinks and sugar--are composed entirely of simple sugars. Potatoes provided around 11% of the fiber, which made them the leading source of fiber. This article shows that the relative ranking of foods and the contribution of each food depend on the way food codes are combined. Therefore, citing one food as the major source of a particular food component without including documentation of how foods are combined can be misleading. PMID- 1310700 TI - Content and composition of dietary fiber in 117 frequently consumed foods. AB - Twenty-three fruits, 33 vegetables, 41 grain products, 7 legumes, 4 nuts, and 9 miscellaneous foods were analyzed by an accurate chemical method to determine their dietary fiber content and composition. The mean (+/- standard deviation) dietary fiber content of fruits was 1.4 +/- 0.7 g/100 g (fresh weight); of vegetables, 2.0 +/- 0.8 g; of 32 refined grains (less than 5% fiber), 2.3 +/- 1.0 g; of legumes, 4.0 +/- 0.7 g; and of nuts, 6.4 +/- 2.1 g; the dietary fiber content of nine higher-fiber grains (greater than 5%) was variable. The soluble fiber fraction averaged 23% of the total fiber in refined grains, 3% in nuts, and 13% to 20% in the other food groups. Dietary fiber composition of every food group was heterogenous. Pectin, which was negligible in grains, constituted approximately 15% to 30% of the fiber in fruits, vegetables, legumes, and nuts. Hemicelluloses composed about half of the total fiber in grains, and approximately 25% to 35% of total fiber in other foods. Cellulose was one third or less of the total fiber in most foods, except for legumes, in which it was about one half. Values for total dietary fiber content generally agree with those reported previously. The soluble fiber fraction was lower than what has been reported because the distribution of total fiber between the soluble and insoluble fractions is determined by the method of analysis. The analyses used in this study demonstrated that the concentration of dietary fiber in many frequently consumed foods is 1% to 3%. The generally similar fiber concentrations of food within a group--fruits, vegetables, refined grains, and legumes--suggest that an average value for the fiber concentration in that group can be used to rank food intakes and histories into low, medium, or high dietary fiber contents. PMID- 1310698 TI - Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-alpha-mediated mechanism. AB - Human cytomegalovirus (HCMV) is a potential cofactor in HIV-1 infection. To investigate the mechanism whereby HCMV promotes HIV-1 replication, a PBMC coculture assay which measures HIV-1 p24 antigen release was used as an index of viral replication. HCMV-stimulated PBMC were capable of inducing HIV-1 replication in cocultures with acutely infected PBMC; however, this occurred only when the PBMC were from HCMV-seropositive donors (598 +/- 207 versus 27 +/- 10 pg/ml p24 antigen with PBMC from HCMV-seronegative donors on day 6 of coculture). Upon stimulation with HCMV, PBMC obtained exclusively from HCMV-seropositive donors released tumor necrosis factor (TNF)-alpha (270 +/- 79 pg/ml at 18 h of culture). Monoclonal antibodies to TNF-alpha blocked the activity of HCMV stimulated PBMC in cocultures both with acutely HIV-1-infected PBMC and with the chronically infected promonocytic line U1. Also, treatment of HCMV-stimulated PBMC with pentoxifylline, an inhibitor of TNF-alpha mRNA, markedly reduced HIV-1 replication in cocultures both with acutely and chronically infected cells. These results indicate that TNF-alpha is a key mediator of HIV-1 replication induced by HCMV-stimulated PBMC and support the concept that this cytokine plays an important role in the pathogenesis of HIV-1 infection. PMID- 1310701 TI - Weight-for-height measurement and saturated fatty acid intake are predictors of serum cholesterol level in children. AB - To assess the relationship of serum cholesterol level to anthropometric measurements and dietary intake, we measured serum cholesterol, height, weight, triceps skinfold, and 24-hour dietary intake in 80 children (mean age = 9.8 years) during April 1989. The mean serum cholesterol level was 3.95 mmol/l. In comparison with national data, weight-for-height and triceps skinfold measurements exceeded the 90th percentile in 18 (23%) and 26 (33%) of the children, respectively. Mean cholesterol and fat intakes were 114 mg/1,000 kcal and 36% of energy, respectively. In multiple stepwise regression analyses, weight for-height measurement and saturated fatty acid intake were most predictive of serum cholesterol levels. Diets of children who consumed 30% of energy or less from fat (low-fat group) met or exceeded the Recommended Dietary Allowances except for energy and vitamin E and were higher in percentage of energy from carbohydrate, dietary fiber, magnesium, iron, and copper than were diets of children who consumed 31% of energy or more from fat (high-fat group). Children in the high-fat group ate more red/processed meats, baked desserts, and fats/oils than children in the low-fat group. Our data indicate that programs to reduce risk of cardiovascular disease in children may need to focus on maintaining ideal body weight and reducing saturated fatty acid intake. PMID- 1310702 TI - Cocaine and marijuana use during pregnancy by women intending and not intending to breast-feed. PMID- 1310703 TI - Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes. AB - A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture supernatants. The results were confirmed by neutralisation assay and ELISAs using recombinant and synthetic polypeptides derived from the c100-3 antigen and from the HCV core antigen. Two patients suffering from non-A, non-B hepatitis were negative for HCV antibodies in serum, but their PBL produced HCV c100-3 antibodies in vitro. PBL from patients suffering from autoimmune chronic hepatitis, primary biliary cirrhosis, toxic-liver injury and healthy blood donors did not produce antibodies to HCV c100 antigen irrespective of HCV antibody test results in their sera. Polyclonal B cell activation or mitogenic stimulation of T helper cells led to increased immunoglobulin synthesis by PBL in vitro, but did not lead to enhancement of specific HCV antibody production. In addition, HCV antibody production was not induced by these stimulation procedures in control lymphocytes. This spontaneous HCV antibody production in vitro suggests persistent antigenic stimulation of the B cells in vivo. PMID- 1310704 TI - Characterization of membrane fraction lipid composition and function of cirrhotic rat liver. Role of S-adenosyl-L-methionine. AB - The effect of S-adenosyl-L-methionine (SAM) administration on the lipid composition of the membrane fraction obtained from livers of cirrhotic rats was studied. Four groups of animals were used: group 1 received CCl4 for 8 weeks to induce cirrhosis. Animals in group 2 received 3 daily i.m. injections of SAM 20 mg/kg in addition to CCl4. Groups 3 and 4 were control groups of SAM and vehicles. Seventy-two h after the end of treatment all animals were killed and livers were studied to measure glycogen, cAMP contents and to isolate membrane fractions. The membrane activity of Na+,K(+)- and Ca(2+)-ATPases was measured and the lipid content was analyzed in extracts. Phospholipids were determined by thin layer chromatography and fatty acids by gas chromatography. Chronic CCl4 treatment led to increases in cholesterol and in the cholesterol/phospholipid ratio. Analysis of phospholipids revealed an increase in phosphatidylserines. Saturated fatty acids increased, while unsaturated decreased significantly. The CCl4-treated group showed a decrease in glycogen and an increase in cAMP contents. Na+,K(+)- and Ca(2+)-ATPases activity were highly reduced in cirrhotic membranes. In the group receiving CCl4 + SAM the lipid composition and the function of liver membrane fraction showed no difference compared to normal controls, except for fatty acid composition which was similar to concentrations in the CCl4-treated group. Glycogen depletion was only partially prevented whereas cAMP levels were normalized in the CCl4 + SAM group. Our results showed that membrane lipid alterations were accompanied by changes in the activity of enzymes embedded in the membrane fraction derived from CCl4-cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310705 TI - Expression of insulin-like growth factor II (IGF-II) and IGF-II, IGF-I and insulin receptors mRNAs in isolated non-parenchymal rat liver cells. AB - The insulin-like growth factor II (IGF-II) is involved in embryonic growth. Modifications of its expression might play a role in the development of primary liver cancer in humans and woodchucks. In the liver, little information is available on the cell types involved in its synthesis. We have investigated the expression of IGF-II as well as IGF-II, IGF-I and insulin receptor mRNAs in non parenchymal liver cell preparations in rats of various ages. The results indicate that Kupffer cells, endothelial cells and fat-storing cells express both IGF-II and the three different receptor mRNAs. Furthermore, a switch from a fetal to an adult IGF-II mRNA profile was obtained in the different cell preparations. Therefore, our results indicate that regulation of IGF-II gene expression can be analyzed through these isolated liver cell preparations. These results might also be important in investigating the potential role of IGF-II in liver carcinogenesis. PMID- 1310706 TI - Clinical backgrounds of the patients having different types of hepatitis C virus genomes. AB - Hepatitis C virus (HCV) genomes were recently detected in biological materials, and variations of nucleotide sequences were reported. In the present study, typing of the HCV genomes was performed in 91 HCV-RNA-positive patients and the clinical features of patients with different types of HCV were compared. From the nucleotide sequences of the cDNA fragments, HCV can be divided into at least two types: HCV-K1-PT and HCV-K2. All cDNAs amplified from 91 patients were hybridized with cDNA probes of either HCV-K1-PT or HCV-K2. HCV-K1-PT was found in about 80% of the patients, and HCV-K2 was found in about 20% of the patients. These results indicate that types of HCV are limited to two types, i.e., K1-PT and K2, and the major type is HCV-K1-PT, at least in Japan. Detection rate of antibodies to C-100 3 protein were not different between the patients having HCV-K1-PT and HCV-K2, indicating that the antibodies may develop in HCV-related patients without relation to the types of the HCV genomes. Prevalence of the two types of HCV were nearly the same in various forms of NANB-related liver disease. However, the prevalence was somewhat different in alcoholic liver disease. HCV-K2 was found in patients younger than the patients with HCV-K1-PT. Frequency of a history of blood transfusion tended to be lower and the initial response to interferon treatment was clearly better in patients having HCV-K2 versus patients having HCV K1-PT. These results suggest the possibility that clinical features due to HCV-K1 may be somewhat different from those due to HCV-K1-PT. However, the number of patients examined was too small to allow a definite conclusion, indicating a necessity for further study with a larger number of patients. PMID- 1310707 TI - Frequency of antibody to hepatitis C virus in asymptomatic HBsAg-negative chronic active hepatitis. AB - To determine the frequency of antibodies to hepatitis C virus in asymptomatic patients with HBsAg-negative chronic active hepatitis, sera from 30 consecutive patients with few or no symptoms of liver disease were tested by an enzyme immunoassay. The reactivity of antibodies detected by enzyme immunoassay against hepatitis C virus encoded antigens was determined by recombinant immunoblot assay. Antibodies were detected in 11 of the 30 patients (37%) and eight of the seropositive sera (73%) were reactive by recombinant immunoblot assay. Nonreactive patients were weakly positive by enzyme immunoassay (sample/cutoff ratio, less than or equal to 1.9) in contrast to reactive patients (sample/cutoff ratio, greater than or equal to 6.3). The prevalence of immunoserologic markers was similar in patients with and without antibodies (78 vs. 87%) but high titers (greater than or equal to 1:160) were more common in seronegative patients (53 vs. 11%). Additionally, seronegative patients had smooth muscle antibodies (83 vs. 25%, p less than 0.05) and concurrent extrahepatic immunologic diseases (37 vs. 9%) more commonly than seropositive counterparts. We conclude that asymptomatic patients with HBsAg-negative chronic active hepatitis frequently have antibodies to hepatitis C virus. These antibodies commonly react to specific viral antigens, especially if the enzyme immunoassay is strongly positive. Seropositive patients infrequently have concurrent immunologic disorders or smooth muscle antibodies. Immunoserologic markers lack diagnostic specificity except in higher titer. PMID- 1310708 TI - Neutrophil chemotactic factors promote leukocytosis. A common mechanism for cellular recruitment from bone marrow. AB - We investigated cellular responses in a rabbit to i.v. administration of five established chemotactic factors (leukotriene B4 (LTB4), platelet-activating factor (PAF), C5a, N-Formyl-Met-Leu-Phe (F-MLF), and IL-8), and each exerted a characteristic effect on circulating white blood cell levels. All five factors induced a rapid and transient leukopenia. The blood was nearly devoid of circulating neutrophils 5 min after administration of each chemotactic factor. Other leukocytes were also variably depleted during the leukopenic phase, including eosinophils, basophils, monocytes, and lymphocytes. The lymphocyte numbers remained significantly depressed (approximately 30%) for as long as 3 h after administration of PAF or f-MLF. Each chemotactic factor produced a marked neutrophilia (i.e., 250-400% of baseline levels) after the initial leukopenia. Eosinophil numbers were elevated along with the neutrophil response in the C5a- and LTB4-treated animals. Basophil levels were significantly elevated only in LTB4-treated animals. The cellular response to PAF, f-MLF, and IL-8 appeared to be specific for the neutrophils. The kinetic profiles of the neutrophilia induced by PAF (10 micrograms/kg) or f-MLF (2.5 micrograms/kg) were similar, with maximal responses occurring 3 to 4 h after administration. In contrast, LTB4 (10 micrograms/kg), IL-8 (2.5 micrograms/kg), and C5a (5 micrograms/kg) induced a more rapid neutrophilia, with peak responses occurring 1 to 1.5 h after injection, and remaining elevated for 3 to 4 h. In all animals the neutrophilia was accompanied by a relative increase in the number of nonsegmented neutrophils (bands), suggesting that a major component of leukocytosis is caused by the release of bone marrow reserves. Phenidone (10 mg/kg), a dual cyclooxygenase/5 lipoxygenase inhibitor, affected neither the neutropenia nor the neutrophilia induced by C5a, f-MLF, or PAF. The protein synthesis inhibitor actinomycin D also failed to suppress neutrophil responses induced by either C5a or PAF. These results suggest that leukocytosis is a common response induced by all neutrophil chemotactic factors. Leukocytosis appears to be a direct result of the dynamic adaptive response of neutrophils to chemotactic factor stimulation without involvement of a secondary mediator system. PMID- 1310709 TI - Differential effects of prostaglandins on macrophage activation induced by calcium ionophore A23187 or IFN-gamma. AB - Calcium ionophore A23187 can mimic IFN-gamma-induced macrophage activation for intracellular Leishmania killing and secretion of L-arginine-derived nitrite. Because the effects of ionophore are not restricted to calcium mobilization but also involve alterations of phospholipid metabolism, we have examined the role of PGE2 in the activation process. Macrophages exposed to A23187 or IFN-gamma in the presence of LPS and FCS secreted significant amounts of PGE2 independently of the presence of L-arginine in the incubation medium. The addition of the cyclooxygenase inhibitor indomethacin or omission of FCS abrogated PGE2 secretion but had little effect on nitrite production or intracellular killing. The addition of exogenous PGE2, of agents increasing PGE2 production such as arachidonic acid and colchicine, or of an analogue of cAMP, dibutyryl cAMP inhibited A23187 + LPS-induced activation whereas that mediated by IFN-gamma + LPS remained unimpaired. Our results indicate that PGE2 can modulate activation induced by A23187 but not by IFN-gamma, probably by a process involving cAMP. Conceivably, ionophore can mimic IFN-gamma for the induction of activation but lacks the capacity to help maintain the activated state because of its inability to desensitize macrophages to negative regulation by PGE2, as suggested previously for IFN-gamma-dependent activation. PMID- 1310710 TI - Developmental regulation of D beta reading frame and junctional diversity in T cell receptor-beta transcripts from human thymus. AB - During fetal life, both Ig and TCR-gamma delta repertoires are enriched for a specific set of Ag receptors with limited diversity. In order to test the hypothesis that diversification of the human TCR-beta repertoire also follows a developmental program, we examined TCR-beta DJ and VDJ transcripts from fetal and adult thymi. A consistent bias for D beta 1.1 and J beta 1.1 was present in DJ transcripts amplified from 8-wk gestation thymi. Although it is possible to splice and translate D beta 1.1 in all three reading frames, 8-wk gestation fetal DJ transcripts were enriched for D beta 1.1 spliced to J beta 1.1 in reading frame one. Preference for D beta 1.1 reading frame one and for use of J beta 1.1 dwindled with increasing gestational age. Reading frame bias was not affected by the insertion of non-germ-line-encoded nucleotides (N regions) or by the site of gene splicing. In contrast, choice of reading frame and use of J beta 1.1 appeared random in VDJ transcripts from the same 8-wk gestation and adult thymic samples. Among the occasional VDJ transcripts that contained D beta 1.1-J beta 1.1 rearrangements, use of D beta reading frame one was rare. Up to 75% of DJ and VDJ transcripts at 8-wk gestation lacked N regions. Both the percentage of DJ and VDJ transcripts with N regions and the average number of inserted nucleotides per transcript increased with gestational age. Primarily as a result of enhanced N region addition, both the length and sequence diversity of the VDJ junctions increased markedly from 8-wk gestation to adult life with a concomitant increase in the potential size of the TCR-alpha beta repertoire. Terminal deoxynucleotidyl transferase (TdT), the enzyme associated with N region addition, has not been detected in thymus before 19 wk of gestation. However, we were able to amplify TdT mRNA from all fetal thymi examined. This suggests that TdT may be expressed as early as 8 wk gestation, although at low levels. The early fetal thymus appears enriched for a population of thymocytes that produce minimal quantities of TdT, express a special set of TCR-beta DJ transcripts, and generate a TCR-beta repertoire with limited diversity. These findings support the hypothesis that limitations in the diversity of the TCR repertoire imposed at the time of gene rearrangement contribute to the immaturity of the fetal immune response. PMID- 1310711 TI - A murine CD4-, CD8- T cell receptor-gamma delta T lymphocyte clone specific for herpes simplex virus glycoprotein I. AB - The role of TCR-gamma delta T lymphocytes in immune responses is currently not well understood. TCR-gamma delta cells have a limited repertoire suggesting that TCR-gamma delta T a limited number of evolutionarily conserved Ag such as nonpolymorphic MHC and heat shock proteins. TCR-gamma delta T lymphocytes appear in enhanced numbers in skin lesions produced by Mycobacterium leprae and in the synovial fluid of joints affected by rheumatoid arthritis, raising the possibility that this subset of T lymphocytes may play a role in control of infectious processes and in autoimmune diseases. We report the identification of a TCR-gamma delta T cell clone isolated from a HSV-infected mouse that recognizes glycoprotein I of HSV type 1. Clone recognition of glycoprotein I does not appear to require the expression of MHC class I or class II gene products. These data suggest that TCR-gamma delta lymphocytes may play an important role in the immune response to viral infections. PMID- 1310712 TI - Pituitary adenylate cyclase-activating polypeptide releases 7B2, adrenocorticotrophin, growth hormone and prolactin from the mouse and rat clonal pituitary cell lines AtT-20 and GH3. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalami and so called because of its ability to stimulate pituitary adenylate cyclase activity. Alternative amidation and proteolytic processing of prepro-PACAP gives rise to two bioactive-amidated forms, PACAP-NH2(1-38) (PACAP-38) and PACAP-NH2(1-27) (PACAP-27). 7B2 is a polypeptide of 185 amino acids which is predominantly found in secretory granules and is widely distributed in rat and human tissues. We investigated the ability of the two forms of PACAP to stimulate GH, prolactin and 7B2 release by the rat pituitary clonal cell line GH3, and ACTH and 7B2 by the mouse pituitary clonal cell line AtT-20. PACAP-38 and PACAP-27 stimulated 7B2 and GH/prolactin or ACTH secretion with a similar efficacy over the 2-h incubation period from GH3 and AtT 20 cells respectively. 7B2 secretion was also stimulated by corticotrophin releasing factor (CRF-41) and vasoactive intestinal polypeptide (VIP) in AtT-20 cells, and thyrotrophin-releasing hormone (TRH) and VIP in GH3 cells. Addition of PACAP to CRF-41 resulted in an additive effect on ACTH secretion and a synergistic effect on 7B2 secretion in AtT-20 cells. No synergism was observed when PACAP was added together with TRH, either on GH and prolactin secretion or on 7B2 release from GH3 cells. PACAP-mediated 7B2 secretion from both cell lines and PACAP-stimulated ACTH release from AtT-20 cells were reduced by 5 mg octapeptide synthetic somatostatin analogue/l (5 mg SMS 201-995/l). PMID- 1310713 TI - Effects of oestradiol-17 beta on FSH-stimulated steroidogenesis in cultured marmoset granulosa cells. AB - A role for oestradiol in ovarian follicular development is well recognized. However, a number of disparate effects have been reported for the action of oestradiol in the primate ovary. To investigate this further, we have examined the effects of oestradiol on the differentiation of granulosa cells isolated from small (0.5-1 mm) antral follicles obtained from the ovaries of prepubertal marmoset monkeys (Callithrix jacchus). Granulosa cells were co-cultured with oestradiol and human FSH (hFSH) for 48 h, or were pretreated with oestradiol for 48 h before addition of gonadotrophin for a further 48 h. Oestradiol (0.01-100 nmol/l) had no effect on basal or hFSH-stimulated progesterone accumulation and aromatase activity when the hormones were added concurrently. Furthermore, oestradiol did not influence the ability of hFSH to induce LH/human chorionic gonadotrophin (hCG) responsiveness in immature granulosa cells. The absence of synergism between oestradiol and hFSH in the induction of marmoset granulosa cell differentiation was independent of the presence of phenol red in culture medium. However, gonadotrophin-stimulated steroidogenesis was attenuated when cells were cultured in the presence of phenol red compared with in its absence; this effect was more pronounced for gonadotrophin-stimulated aromatase activity but was evident for LH/hCG-stimulated progesterone accumulation at higher doses of hCG (10 and 100 ng/ml). An effect of phenol red on basal steroidogenesis was less obvious.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310714 TI - Prostaglandin E2 enhances AVP-stimulated but not CRF-stimulated ACTH secretion from cultured fetal sheep pituitary cells. AB - This study examined the ability of prostaglandin E2 (PGE2) to regulate ACTH secretion from cultured anterior pituitary cells of fetal sheep between days 130 and 140 of gestation (term = 145 days). Corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) induced dose-dependent (0.1-1000 nmol/l) increases in ACTH secretion from fetal sheep pituitary cells maintained in culture for 6 days, with AVP being significantly (P less than 0.01) more potent than CRF. PGE2 (1000 nmol/l) significantly (P less than 0.05) enhanced the ability of AVP, but not CRF, to stimulate ACTH secretion. However, PGE2 given alone (0.1-1000 nmol/l) had no effect on ACTH secretion. Concomitant administration of CRF and AVP induced a greater release of ACTH than after treatment with either peptide alone, a synergistic interaction which was unaffected by simultaneous administration of PGE2. These results provide evidence for a direct action of PGE2 on ACTH secretion from the fetal sheep pituitary gland via a specific interaction with AVP. This interaction may allow increased fetal plasma concentrations of PGE2, seen during late gestation, to stimulate fetal pituitary-adrenal maturation. PMID- 1310715 TI - Comparison of three-day temafloxacin with seven-day ciprofloxacin treatment of urinary tract infections in women. AB - BACKGROUND: Temafloxacin is a new broad-spectrum arylfluoroquinolone antimicrobial with an extended serum half-life. METHODS: In this large, multicenter, double-blind clinical trial, 404 women with acute, uncomplicated urinary tract infections (UTI) were randomized to receive temafloxacin 400 mg once daily for 3 days, or ciprofloxacin 250 mg twice daily for 7 days. Clinical and microbiologic evaluations were repeated at 4 to 5 days after initiation of treatment, at the end of therapy, and at 5 to 9 days posttreatment. One hundred fifteen patients who received temafloxacin and 105 patients who received ciprofloxacin met the eligibility criteria for efficacy evaluation. The predominant urinary pathogens were Escherichia coli, Proteus mirabilis, and coagulase-negative staphylococci. No pretherapy isolate was resistant to either study drug. RESULTS: Bacteriologic eradication was observed in 112 (97%) of 115 women treated with temafloxacin and 101 (96%) of 105 women treated with ciprofloxacin. Clinical cure rates at 5 to 9 days posttreatment were 90% (the remaining 10% improved) with temafloxacin and 95% (the remaining 5% improved) with ciprofloxacin. Adverse effects associated with treatment occurred in 24 (12%) women who received temafloxacin and 31 (15%) women who received ciprofloxacin. Headache (2% with temafloxacin and 2% with ciprofloxacin), nausea (3% with temafloxacin and 6% with ciprofloxacin), and somnolence (4% with temafloxacin and 3% with ciprofloxacin) were reported most often. Only three and five patients who were treated with temafloxacin and ciprofloxacin, respectively, discontinued treatment because of adverse effects. CONCLUSIONS: In this study, a 3-day treatment regimen using a single daily 400-mg dose of temafloxacin was found to be as effective as a 7-day course of ciprofloxacin in women with acute uncomplicated UTI. PMID- 1310716 TI - Effects of forskolin, dibutyryl cyclic AMP, and 5'-N-ethylcarboxamide adenosine on 22Na uptake by rat brain synaptosomes stimulated by veratridine. AB - The effects of forskolin, dibutyryl cyclic AMP, and 5'-N-ethylcarboxamide adenosine on specific 22Na uptake by synaptosomes stimulated by veratridine were investigated. All substances inhibited 22Na uptake, with forskolin more potent than 5'-N-ethylcarboxamide and this latter one more potent than dibutyryl cyclic AMP. In the absence of preincubation with forskolin, this substance caused little or no effect on 22Na uptake by synaptosomes. In the presence of the adenosine antagonist dipropylsulfophenylxanthine, the inhibitory effect of 5'-N ethylcarboxamide adenosine on 22Na uptake was consistently antagonized. The results were interpreted as forskolin and 5'-N-ethylcarboxamide adenosine increasing cyclic AMP accumulation, and dibutyryl cyclic AMP mimicking it, and by these mechanisms decreasing sodium uptake through the sodium channels. PMID- 1310717 TI - Ouabain binding, ATP hydrolysis, and Na+,K(+)-pump activity during chemical modification of brain and muscle Na+,K(+)-ATPase. AB - The effects of 16 group-specific, amino acid-modifying agents were tested on ouabain binding, catalytical activity of membrane-bound (rat brain microsomal), sodium dodecyl sulfate-treated Na+,K(+)-ATPase, and Na+,K(+)-pump activity in intact muscle cells. With few exceptions, the potency of various tryptophan, tyrosine, histidine, amino, and carboxy group-oriented drugs to suppress ouabain binding and Na+,K(+)-ATPase activity correlated with inhibition of the Na+,K(+) pump electrogenic effect. ATP hydrolysis was more sensitive to inhibition elicited by chemical modification than ouabain binding (membrane-bound or isolated enzyme) and than Na+,K(+)-pump activity. The efficiency of various drugs belonging to the same "specificity" group differed markedly. Tyrosine-oriented tetranitromethane was the only reagent that interfered directly with the cardiac receptor binding site as its inhibition of ouabain binding was completely protected by ouabagenin preincubation. The inhibition elicited by all other reagents was not, or only partially, protected by ouabagenin. It is surprising that agents like diethyl pyrocarbonate (histidine groups) or butanedione (arginine groups), whose action should be oriented to amino acids not involved in the putative ouabain binding site (represented by the -Glu-Tyr-Thr-Trp-Leu-Glu- sequence), are equally effective as agents acting on amino acids present directly in the ouabain binding site. These results support the proposal of long-distance regulation of Na+,K(+)-ATPase active sites. PMID- 1310719 TI - Ischemia-induced loss of brain calcium/calmodulin-dependent protein kinase II. AB - Forebrain ischemia in gerbils, produced by brief bilateral carotid occlusion, induced the dramatic loss of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) as determined by both kinase activity assays and western blot analysis. In cortex and hippocampus, cytosolic CaM-kinase II was completely lost within 2-5 min of ischemia. Particulate CaM-kinase II was more stable and decreased in level approximately 40% after 10 min of ischemia followed by 2 h of reperfusion. CaM-kinase II in cerebellum, which does not become ischemic, was not affected. The rapid loss of CaM-kinase II within 2-5 min was quite specific because cytosolic cyclic AMP kinase and protein kinase C in hippocampus were not affected. These data indicate that cytosolic CaM-kinase II is one of the most rapidly degraded proteins after brief ischemia. Because the multifunctional CaM kinase II has been implicated in the regulation of numerous neuronal functions, its loss may destine the neuronal cell for death. PMID- 1310718 TI - Down-regulation of beta-adrenergic receptors by pindolol in Gs alpha-transfected S49 cyc- murine lymphoma cells. AB - The role of the alpha subunit of the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase (GS alpha) in the down-regulation of beta-adrenergic receptors by pindolol was studied in S49 cyc- cells (normally GS alpha-deficient) transfected to express functional recombinant rat GS alpha. An inducible cell line (S49 GS alpha IND) was derived from S49 cyc- cells transfected with a vector containing the full-length coding sequence of GS alpha under the inducible control of the mouse mammary tumor virus long-terminal repeat promoter. GS alpha was not detectable in S49 GS alpha IND cells by immunoblot or by ADP-ribosylation in the presence of cholera toxin and [alpha-32P]NAD. When cells were grown in 100 nM dexamethasone, isoproterenol-stimulated cyclic AMP accumulation increased within 3 h. After 15 h, GS alpha was present at a level 40 50% of that found in S49 wild-type (WT) cells as measured either by immunoblot analysis or by [alpha-32P]ADP-ribosylation. Membranes prepared from GS alpha IND cells grown in the presence of dexamethasone bound agonist with high affinity, and this binding was sensitive to guanine nucleotides. A second vector, DzbGS alpha +, contained the coding sequence of GS alpha under the constitutive regulatory control of the SV40 early promoter. This vector was introduced into cyc- cells, and the resulting cells, S49 GS alpha CST cells, expressed GS alpha at a level comparable to that found in S49 WT cells as measured by immunoblot analysis. Isoproterenol-stimulated cyclic AMP accumulation in S49 GS alpha CST cells was at least as great as in S49 WT cells. When cells were grown in the presence of dexamethasone, exposure to 50 nM pindolol for 12 h down-regulated the density of beta-adrenergic receptors in S49 WT cells to 60% of that in cells grown in the absence of pindolol, but pindolol had no effect on the density of receptors on cyc- or GS alpha IND cells. When GS alpha CST cells were exposed to 50 nM pindolol for 12 h, the density of beta-adrenergic receptors was down regulated by the same amount as in S49 WT cells. These results suggest that GS alpha is necessary to restore the ability of pindolol to down-regulate beta adrenergic receptors in S49 cyc- cells and that the protein must be expressed at a level comparable to that found in S49 WT cells. PMID- 1310720 TI - Hydroxylated analogues of 5-aminovaleric acid as 4-aminobutyric acidB receptor antagonists: stereostructure-activity relationships. AB - The (R) and (S) forms of 5-amino-2-hydroxyvaleric acid (2-OH-DAVA) and 5-amino-4 hydroxyvaleric acid (4-OH-DAVA) were designed as structural hybrids of the 4 aminobutyric acidB (GABAB) agonist (R)-(-)-4-amino-3-hydroxybutyric acid [(R)-(-) 3-OH-GABA] and the GABAB antagonist 5-aminovaleric acid (DAVA). (S)-(-)-2-OH-DAVA and (R)-(-)-4-OH-DAVA showed a moderately potent affinity for GABAB receptor sites in rat brain and showed GABAB antagonist effects in a guinea pig ileum preparation. The respective enantiomers, (R)-(+)-2-OH-DAVA and (S)-(+)-4-OH-DAVA, were markedly weaker in both test systems. All four compounds were weak inhibitors of GABAA receptor binding in rat brain, and none of them significantly affected synaptosomal GABA uptake. Based on molecular modeling studies it has been demonstrated that low-energy conformations of (R)-(-)-3-OH-GABA, (S)-(-)-2 OH-DAVA, and (R)-(-)-4-OH-DAVA can be superimposed. These conformations may reflect the shapes adopted by these conformationally flexible compounds during their interaction with GABAB receptors. The present studies emphasize the similar, but distinct, constraints imposed on agonists and antagonists for GABAB receptors. PMID- 1310721 TI - Increased superoxide dismutase activity in aged human cerebrospinal fluid and rat brain determined by electron spin resonance spectrometry using the spin trap method. AB - Superoxide dismutase (SOD) activity in CSF of patients was determined by electron spin resonance spectrometry using the spin trap method. Variation in SOD activity was found among patients. SOD activity in CSF of subjects increased with age and this was identified as Cu,Zn-SOD activity by electrophoresis. In addition, animal experiments showed that SOD activities were higher in mitochondrial and cytosol fractions of aged rats than in those of adult rats. This finding on aged rat brain validates the increase of SOD activity in aged human CSF. PMID- 1310722 TI - Expression of olfactory receptors in Xenopus oocytes. AB - The rat olfactory epithelium and the amino acid-sensitive catfish olfactory system have been used as models to study the molecular mechanisms of olfactory transduction. Here we report the functional expression of rat and catfish olfactory receptors in Xenopus oocytes injected with mRNA isolated from the respective tissues. Application of odor ligands to injected oocytes, monitored by two-electrode voltage clamp, activates stimulus-dependent transmembrane currents that reverse direction at about the chloride equilibrium potential. The currents show characteristic secondary oscillations that are presumed to reflect underlying Ca2+ oscillations. Similar ligand-activated membrane currents induced in oocytes after injection of other mRNAs have been shown to be due to activation of endogenous Ca(2+)-activated chloride channels. In summary, our results demonstrate the usefulness of the Xenopus oocyte expression system for cloning and characterization of olfactory receptors in both fish and mammalian species. PMID- 1310723 TI - Highly ouabain-sensitive alpha 3 isoform of Na+,K(+)-ATPase in human brain. AB - The Na+,K(+)-ATPase alpha 3 isoform has recently been demonstrated immunochemically in human brain. Conclusive biochemical evidence, however, is still lacking. In this study, a unique 50-kDa polypeptide, which is known to be specific to the rat alpha 3 isoform, has been found in human brainstem Na+,K(+) ATPase following formic acid treatment of the purified alpha isoform proteins. Human alpha 3 Na+,K(+)-ATPase is also highly sensitive to ouabain inhibition, with a 50% ouabain inhibition value of 1.0 x 10(-7) M. These results provide clear and direct evidence for the existence of the alpha 3 isoform in human brain. PMID- 1310724 TI - Inhibition of cyclic AMP formation by a selective metabotropic glutamate receptor agonist. AB - It is well documented that the effects of excitatory amino acid (EAA) agonists on phosphoinositide hydrolysis involve a GTP-binding protein-linked or "metabotropic" receptor mechanism. The mechanisms by which EAAs alter cyclic AMP levels in brain slices, however, are not yet clear. In this study, the selective metabotropic EAA agonist trans-(+-)-1-aminocyclopentane-1,3-dicarboxylic acid and its isomers were examined for effects on basal and forskolin-stimulated cyclic AMP formation in slices of the rat hippocampus. Trans-(+-)-1-Aminocyclopentane 1,3-dicarboxylic acid had little effect on basal cyclic AMP but inhibited forskolin-stimulated cyclic AMP formation in a biphasic manner. The 1S,3R isomer of 1-aminocyclopentane-1,3-dicarboxylic acid produced potent but only partial (approximately 50%) inhibition of forskolin-stimulated cyclic AMP formation. 1R,3S-1-Aminocyclopentane-1,3-dicarboxylic acid fully inhibited forskolin stimulated cyclic AMP but with lower potency than the 1S,3R isomer. These results show that in addition to the formation of phosphoinositide-derived second messengers, the cellular consequences of selectively activating hippocampal metabotropic EAA receptors include an alteration of cellular cyclic AMP levels. PMID- 1310725 TI - Activation of microtubule-associated protein kinase in PC12D cells in response to both fibroblast growth factor and epidermal growth factor and concomitant stimulation of the outgrowth of neurites. AB - When PC12D cells, a subline of PC12 cells, were cultured with nerve growth factor (NGF), outgrowth of neurites was promoted even when RNA synthesis was blocked. This property of PC12D cells may enable us to resolve the mechanism of the outgrowth of neurites that is induced in a transcription-independent manner. The outgrowth of neurites from PC12D cells was also stimulated in response to fibroblast growth factor (FGF) and was slightly stimulated in response to epidermal growth factor (EGF). The brief exposure of intact PC12D cells not only to NGF but also to FGF or to EGF stimulated a protein kinase activity in extracts of such cells that catalyzed phosphorylation of microtubule-associated protein 1 (MAP-1) and MAP-2 in vitro. Similar dose-response relationships for the effects of NGF and of FGF on the activation of the kinase and on the outgrowth of neurites were observed. The effects of combinations of NGF and GFG or EGF were not additive in terms of either the outgrowth of neurites or the increase in the kinase activity. Treatment of cells with phorbol 12-myristate 13-acetate (PMA) also stimulated the kinase activity that phosphorylated MAPs in vitro. However, the level of the enzymatic activity that resulted from the combined treatment of cells with PMA and NGF was additive, as is the case with dibutyryl cyclic AMP and NGF. These findings suggest that NGF, FGF, and EGF may stimulate the activity of the same MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310727 TI - Gene expression and receptor binding of insulin-like growth factor-II in pig choroid plexus epithelial cells. AB - To elucidate the function of insulin-like growth factor-II (IGF-II) in the choroid plexus, the gene expression and receptor binding of IGF-II were studied in isolated epithelial cells from the porcine choroid plexus. The choroid plexus expressed multiple IGF-II transcripts of 1.2, 1.6, 2.4, and 4.4 kb, at levels higher than those found in porcine liver and kidney. These data suggest that IGF II is synthesized by the choroid plexus. Choroid plexus epithelial cells contained high levels of IGF-I receptors on the cell surface whereas very low levels of receptor binding were found for 125I-IGF-II and 125I-insulin. Solubilization of epithelial cells showed that a large proportion of the IGF-I receptors were present in the detergent-insoluble fraction whereas IGF-II receptors and insulin receptors were concentrated in the detergent-soluble fraction. These results suggest that IGF-I receptors are located in clathrin coated pits of the plasma membrane whereas IGF-II receptors and insulin receptors are present in endosomal vesicles. The tyrosine kinase activity of the IGF-I receptor beta-subunit was stimulated by IGF-I, IGF-II, and insulin, in order of potency, suggesting that these peptides exert a regulatory function in the choroid plexus epithelium. In conclusion, we propose that the IGF-I receptor tyrosine kinase on the surface of the epithelial cells in the pig choroid plexus mediates effects of IGF-I and IGF-II, whereas IGF-II receptors are down-regulated due to the synthesis and secretion of IGF-II in these cells. PMID- 1310726 TI - Opioid control of the in vitro release of cholecystokinin-like material from the rat substantia nigra. AB - Possible interactions between Met-enkephalin and cholecystokinin (CCK)-containing neurons in the rat substantia nigra were investigated by looking for the effects of various opioid receptor ligands and inhibitors of enkephalin-degrading enzymes on the K(+)-evoked overflow of CCK-like material (CCKLM) from substantia nigra slices. The delta-opioid agonists D-Pen2, D-Pen5-enkephalin (50 microM) and Tyr-D Thr-Gly-Phe-Leu-Thr (DTLET; 3 microM) enhanced, whereas the mu-opioid agonists Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO; 10 microM) and MePhe3, D-Pro4-morphiceptin (PL 017; 10 microM) decreased, the K(+)-evoked release of CCKLM. By contrast, the kappa-opioid agonist U-50488 H (5 microM) was inactive. The stimulatory effect of DTLET could be prevented by the delta antagonist ICI-154129 (50 microM), but not by the mu antagonist naloxone (1 microM). Conversely, the latter drug, but not ICI-154129, prevented the inhibitory effect of DAGO and PL 017. A significant increase in CCKLM overflow was observed upon tissue superfusion with the peptidase inhibitors kelatorphan or bestatin plus thiorphan. This effect probably resulted from the stimulation of delta-opioid receptors by endogenous enkephalins protected from degradation, because it could be prevented by ICI-154129 (50 microM). Furthermore the peptidase inhibitors did not enhance CCKLM release further when delta-opioid receptors were stimulated directly by DTLET (3 microM). These data indicate that opioids acting on delta and mu receptors may exert an opposite influence, i.e., excitatory and inhibitory, respectively, on CCK containing neurons in the rat substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310728 TI - Characterization of neuronal protein phosphatases in Aplysia californica. AB - Biochemical properties of neuronal protein phosphatases from Aplysia californica were characterized. Dephosphorylation of phosphorylase alpha by extracts of abdominal ganglia and clusters of sensory neurons from pleural ganglia was demonstrated. Type-1 protein phosphatase (PrP-1) was identified in these extracts by the dephosphorylation of the beta-subunit of phosphorylase kinase and its inhibition by the protein, inhibitor-2. Type-2A protein phosphatase (PrP-2A) was demonstrated by the dephosphorylation of the alpha-subunit of phosphorylase kinase, which was insensitive to inhibitor-2. As in vertebrate tissues, only four enzymes, PrP-1 (47%), PrP-2A (42%), PrP-2B (11%), and PrP-2C (less than 1%), accounted for all the cellular protein phosphatase activity dephosphorylating phosphorylase kinase. Aplysia PrP-1 and PrP-2A were potently inhibited by okadaic acid, with PrP-1 being approximately 20-fold more sensitive than PrP-2A. By comparison, purified PrP-2A from rabbit skeletal muscle was 15- to 20-fold more sensitive to okadaic acid than PrP-1 from the same source. Only PrP-1 was associated with the particulate fractions from Aplysia neurons, whereas PrP-1 and PrP-2A, -2B, and -2C were all present in the cytosol. Extraction of the particulate PrP-1 decreased its sensitivity to okadaic acid by sixfold, suggesting that cellular factor(s) affect its sensitivity to this inhibitor. In most respects, protein phosphatases from Aplysia neurons resemble their mammalian counterparts, and their biochemical characterization sets the stage for examining the role of these enzymes in neuronal plasticity, and in learning and memory. PMID- 1310729 TI - A freeze-fracture study of the perineurium in galactose neuropathy: morphological changes associated with endoneurial oedema. AB - Feeding rats with galactose as 40% of their diet results in peripheral nerve oedema related to the intrafascicular accumulation of galactitol and sodium. In this study, associated changes in the perineurium were examined by the freeze fracture replication technique. Perineurial cells are linked by tight junctions (zonulae occludentes). In normal animals these are made up of anastomosing strands organized in a belt-like arrangement along the margins of continuous cells. The majority of the tight junctions in the galactose-fed animals displayed structural abnormalities. These ranged from slight separation of the strands to fragmentation and dispersal, with looping of isolated strands. Some of the tight junctions contained large dilated compartments within the junctional network. Short lengths of intramembranous particles, probably representing assembly or disassembly of tight junctional strands, were also observed. The membranes of perineurial cells normally possess numerous openings of caveolae. A quantitative assessment showed that the mean density of these caveolae openings was increased in the galactose-fed rats as compared with controls. The alterations in the tight junctions resemble those that have been produced experimentally in epithelia by subjecting them to abnormal osmotic gradients. They also resemble those seen in human diabetic neuropathy in which osmotic disturbances involving the perineurium have been considered to occur. If the alterations involve the inner layers of the perineurium, they are likely to impair its barrier function. The increased number of caveolae openings in galactose neuropathy may represent a reaction to the endoneurial oedema and indicate that the pinocytotic-like vesicles have a transport function. PMID- 1310730 TI - Ultrasound diagnosis of an intraneural ganglion cyst of the peroneal nerve. Case report. AB - The authors present the case of an intraneural ganglion cyst of the peroneal nerve. The cyst was diagnosed by means of ultrasound, which also gave an exact definition of its size and location, confirmed at operation. Some controversial aspects of these lesions are discussed. PMID- 1310731 TI - Anemia in experimental visceral leishmaniasis in hamsters. AB - Experimental infection of hamsters with Leishmania donovani caused visceral leishmaniasis in which hematological changes occurred. The infected hamsters were anemic and reticulocyte counts were high. No significant change in the serum erythropoietin level was noted. Red cell membrane Na(+)-K(+)-ATPase and acetylcholinesterase activities increased. Osmotic fragility of the erythrocytes from infected animals increased. The level of 2,3-diphosphoglycerate of the red cells increased with the degree of anemia. PMID- 1310732 TI - Interactions between Trichomonas vaginalis and vaginal flora in a mouse model. AB - To study the role of vaginal flora and pH in the pathogenesis of Trichomonas vaginalis, an intravaginal mouse model of infection was established. By employing this model, the vaginal flora and pH of mice could be monitored for changes caused by the parasite. As a baseline, the endemic vaginal flora of BALB/c mice was examined first and found to consist mainly of Staphylococcus aureus and Enterococcus species (32-76%). Lactobacilli and enteric bacilli were moderate (16 32%) in their frequency of isolation, and the prevalence of both anaerobic species and coagulase-negative staphylococci was low (4-16%). Vaginal pH was recorded at 6.5 +/- 0.3. Estrogenization, which was required for a sustained T. vaginalis infection, did not significantly alter vaginal flora; however, a slight rise in the number of bacterial species isolated per mouse and a drop in vaginal pH (6.2 +/- 0.5) were observed. Trichomonas vaginalis-infected mice did not appear to show significant changes in vaginal flora although vaginal pH was slightly increased. This mouse model could have applications in both immunologic and pathogenic studies of T. vaginalis and, with further modifications, aid in the study of protist-bacterial interactions. PMID- 1310733 TI - Ribosomal DNA restriction analysis and synthetic oligonucleotide probing in the identification of genera of lower trypanosomatids. AB - Fifty-four species or isolates of insect trypanosomatids were examined for the presence of selected restriction enzyme sites in the small (SSU) and large (LSU) rRNA coding units of ribosomal genes. In the SSU, sites for Eco RI, Bgl II, Pst I, and Hind III were found to occur at the same location for all species examined, thus displaying a universal distribution among trypanosomatids. In the LSU, a site for Bgl II in the 24S-alpha sequence and sites for Hind III and Pst I in the 24S-beta sequence were found in all species examined. In contrast, a site for Pvu II in the SSU exhibited a genus-related distribution, being present in Crithidia and Herpetomonas but absent in Phytomonas. A site for Hind III in the 24S-alpha sequence of the LSU also exhibited genus-restricted distribution. The site was present in Crithidia but absent in Phytomonas and Herpetomonas. These findings were confirmed by dot hybridization with a synthetic oligonucleotide complementary to the 18S rRNA sequence containing the Pvu II site. Results point to the usefulness of restriction markers as diagnostic tools for distinguishing the lower trypanosomatid genera Crithidia, Herpetomonas, and Phytomonas at the same time revealing a marked complexity within the genus Leptomonas. PMID- 1310734 TI - Decreases in unintegrated HIV DNA are associated with antiretroviral therapy in AIDS patients. AB - Better markers are needed to monitor the efficacy of antiretroviral drugs in persons infected with human immunodeficiency virus (HIV). We investigated the effects of zidovudine (ZDV) and dideoxycytidine (ddC) on the presence of unintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from AIDS patients. DNA was extracted from PBMCs and separated into low molecular weight (unintegrated) and high molecular weight (integrated) chromosomal fractions. These DNA fractions were then amplified by a quantitative polymerase chain reaction (PCR) and the amount and percentage of unintegrated HIV DNA were determined. Very high levels of unintegrated HIV DNA were found in AIDS patients not receiving treatment with ZDV or ddC (median = 95% unintegrated HIV DNA). In contrast, most patients who had received 4 or more weeks of antiretroviral therapy had lower levels of unintegrated HIV DNA (median = 30% unintegrated HIV DNA for patients receiving ZDV). Paired samples taken from five patients before and after therapy showed a striking reduction in the percentage of unintegrated HIV DNA. The decrease in the proportion of unintegrated HIV DNA in AIDS patients was due to both a reduction in the copy number of unintegrated HIV DNA and an increase in the copy number of integrated HIV DNA. Thus, measurements of unintegrated and integrated HIV DNA may be useful in providing objective assessments of the effectiveness of antiretroviral therapies. PMID- 1310735 TI - Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels. AB - The vasodilator activity of adenosine has been associated with selective stimulation of A2 receptors. In the present study, the vasorelaxant (VR) activity of an A1-selective agonist, CPA (cyclopentyladenosine), was examined in isolated porcine coronary arterial rings precontracted with prostaglandin F2 alpha and compared to the A2-selective agonist DPMA (N6-[2-(3,5-dimethoxyphenyl)-2-(2 methylphenyl)-ethyl] adenosine). DPMA, approximately 13-fold selective for the rat brain A2 receptor, relaxed isolated coronary arterial rings with an EC50 of 0.59 +/- 0.19 microM (n = 23) whereas CPA, 2200-fold selective for the rat brain A1 receptor, was approximately 5-fold less potent with an EC50 of 3.18 +/- 0.6 microM (n = 11). At low concentrations (10-300 nM) CPA caused vasoconstriction, indicative of the A1-selective nature of this agonist. CGS 15943 (100 nM), a nonselective adenosine antagonist, attenuated the VR activity of DPMA and CPA, causing a 9- and 12-fold rightward shift of the dose-response curves, respectively, whereas 8-cyclopentyl-1,3-dipropylxanthine (20 nM), a highly A1 selective blocker, had no such effect. Both adenosine antagonists abolished the vasoconstrictor response of CPA at low concentrations. The contributions of the cyclic GMP pathway to adenosine-induced VR was assessed using an inhibitor of endothelium-dependent relaxing factor (L-nitroarginine). L-nitroarginine had no effect on the EC50 for CPA-induced VR and, marginally, but not significantly, attenuated DPMA effects. Moreover, no elevation in cyclic GMP levels could be observed in tissues stimulated with CPA or DPMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310736 TI - The catecholamine-mediated positive inotropic effect of simple quinones is related to superoxide anion generation. AB - In guinea pig and rat cardiac tissue, redox cycling benzoquinones (2,5-dimethyl-p benzoquinone and duroquinone) and naphthoquinones (menadione and 2,3-dimethoxy 1,4-naphthoquinone) generated superoxide anion (O2-.) both through one- and two electron reductions, the generation being significantly greater in guinea pig than in rat tissue. In electrically driven left atria isolated from guinea pig and rat, menadione and 2,5-dimethyl-p-benzoquinone but not duroquinone caused a concentration-dependent positive inotropic effect. Unlike guinea pig, 2,3 dimethoxy-1,4-naphthoquinone had no effect in rat tissue. Naphthoquinones and 2,5 dimethyl-p-benzoquinone were more active in guinea pig than in rat tissue, their effect being dependent on the release of catecholamines from adrenergic stores. A linear relationship (r = 0.90) between the amount of O2-. generated by benzo- and naphthoquinones in guinea pig and rat heart and the extent of catecholamine dependent positive inotropic effect was evident. An amount of O2-. higher than 600 nmol/g of tissue per min was calculated to be necessary to determine the catecholamine-mediated increase in contractility. Lipid peroxidation was not involved in quinone-induced catecholamine release. PMID- 1310737 TI - Spinal opioid delta antinociception in the mouse: mediation by a 5'-NTII sensitive delta receptor subtype. AB - Previous studies from our laboratory have indicated that i.c.v. pretreatment of mice with the novel, selective opioid delta receptor antagonists, [D Ala2,Leu5,Cys6]enkephalin (DALCE) and naltrindole-5'-isothiocyanate (5'-NTII), differentially antagonized the direct antinociceptive effects of [D-Pen2,D Pen5]enkephalin (DPDPE) and [D-Ala2]deltorphin II (DELT). These findings, and others, suggested the existence of subtypes of opioid delta receptors which could be classified as activated by DPDPE and DALCE sensitive (delta 1 receptor), or selectively activated by DELT and 5'-NTII sensitive (delta 2 receptor). The present study has extended these observations to the characterization of delta mediated antinociception effects of DPDPE and DELT after i.t. administration in mice using pretreatment with DALCE and 5'-NTII in order to selectively antagonize the delta subtypes. Additionally, the acute antinociceptive actions of DALCE itself were studied to ensure activity of this compound at the spinal level. The respective antinociceptive A50 value (95% CL) for i.t. DPDPE, DELT and DALCE were 19.0 (12.9-28.1), 19.3 (16.1-23.1) and 2.0 (1.4-3.0) nmol. The delta antagonist, N,N-diallyl-Try-Aib-Aib-Phe-Leu-OH (ICI 174,864) (where Aib is alpha aminoisobutyric acid) blocked the antinociceptive effects of DPDPE and DELT, but not those of i.t. morphine or [D-Ala2,NMPhe4,Gly-ol5]enkephalin (DAMGO), indicating that the observed antinociceptive effects of DPDPE and DELT were delta mediated. Pretreatment 24 hr before testing with graded doses of i.t. 5'-NTII blocked the i.t. antinociceptive effects of DPDPE and DELT, although at least a 10-fold higher dose of 5'-NTII was needed to produce equivalent antagonism of DPDPE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310738 TI - Chronic morphine administration impairs cell-mediated immune responses in swine. AB - Swine were used as an experimental animal model to evaluate immunomodulating effects of the opiate drug, morphine, on antigen-specific humoral and cell mediated immune responses. Morphine free base in peanut oil was administered at 4 day intervals for up to 42 days to maintain drug levels at or above 100 ng/ml. The effect of morphine administration on humoral immune responses was evaluated by immunization on day 7 of morphine treatment with a battery of antigens, including swine herpes virus (also known as pseudorabies virus, PRV), Brucella abortus and the Escherichia coli pilus antigens K88, K99, 987P and F41. Fourteen days later, swine were reimmunized with B. abortus and E. coli pilus antigens. Antibody titers to these antigens were evaluated on a weekly basis. Cell-mediated immunity was evaluated by measuring skin immune responses to the antigen 2,4 dintroflurobenozene (DNFB). In one experiment, swine were sensitized with DNFB on day 7 of morphine treatment at the same time as immunization with the other antigens. In a second series of experiments, swine were sensitized either 7 days before or 7 days after initiation of morphine treatment. Pigs were challenged with DNFB administered 27 days after the initiation of morphine treatment and skin responses were evaluated 24 h later. The ability of swine to resist PRV infection was evaluated by exposure to virulent virus on day 28 of morphine treatment. Chronic morphine administration did not impair the induction of the humoral immune responses to bacterial or viral antigens. In addition, morphine treatment did not alter the resistance of immunized swine to PRV infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310739 TI - Interaction of non-arginine compounds with the endothelium-derived relaxing factor inhibitor, NG-monomethyl L-arginine. AB - NG-Monomethyl L-arginine (L-NMMA) inhibits endothelium-dependent relaxation. It is widely accepted that this effect is due to the inhibition of L-arginine metabolism. Here we show that L-NMMA antagonizes the vasodilator effects of compounds other than L-arginine. In the endothelium intact rat aorta preparation, L-NMMA antagonizes the relaxation induced by N-alpha-benzoyl L-arginine ethyl ester, amiloride and dibutyryl cAMP. This effect of L-NMMA is not due to the inhibition of the basal release of endothelium-derived relaxing factor since relaxations of amiloride and dibutyryl cAMP are not significantly different in the presence or absence of endothelium. Addition of superoxide dismutase significantly attenuates the vasoconstrictor effect of L-NMMA and restores the endothelium-dependent relaxation, demonstrating that superoxide anion may be involved in the vascular effects elicited by L-NMMA. Paradoxically, at concentrations greater than 1 mM, L-NMMA elicits endothelium-independent relaxation, which is antagonized by methylene blue. The relaxation elicited by L NMMA is accompanied by the formation of a citrulline-like product in the rat aorta. Thus, L-NMMA has properties other than simple inhibition of L-arginine metabolism in the rat aorta preparation. PMID- 1310740 TI - Mechanism of relaxation induced by K+ and nicotine in dog duodenal longitudinal muscle. AB - Dog duodenal longitudinal muscle strips precontracted with bradykinin responded to K+ (10 mM) with a transient relaxation, which was abolished by tetrodotoxin and oxyhemoglobin, but not influenced by atropine, ouabain and apamin. The induced relaxation was suppressed by treatment with 10(-5) M NG-nitro-L-arginine (L-NNA) a nitric oxide synthesis inhibitor, but not by the D-enantiomer. The inhibitory effect was antagonized by L- but not D-arginine. High concentrations (20 mM or higher) of K+ produced a relaxation followed by a sustained contraction; nicardipine abolished the contraction, but did not alter the relaxation. Nicotine produced a contraction, which was converted to a relaxation by atropine. The relaxant response was abolished by tetrodotoxin, hexamethonium and oxyhemoglobin, but was unaffected by timolol and phentolamine. L-NNA suppressed the relaxation, and L-arginine reversed the inhibition. The addition of K+ (20 mM) increased the content of cyclic GMP in the strips, the effect being prevented by tetrodotoxin and L-NNA. These findings suggest that K+ selectively stimulates the nonadrenergic inhibitory nerve, whereas nicotine stimulates both the excitatory cholinergic and inhibitory nerves. Nitric oxide released from the inhibitory nerve appears to transmit information to duodenal smooth muscle by increasing the production of cyclic GMP. PMID- 1310741 TI - Pharmacological characterization of in vivo [3H]lfenprodil binding sites in the mouse brain. AB - Intravenous injection of 5 muCi of [3H]ifenprodil to mice resulted in an accumulation of radioactivity in the whole brain which was maximal at 5 min postinjection and then declined in a biphasic manner. When whole brain radioactivity was measured 2 h after [3H]ifenprodil injection, more than 65% of the incorporated label was displaced by i.p. administration (30 min before the radiotracer) of the ifenprodil chemical congener +/-alpha-(4-chlorophenyl)-4-(4- fluorophenylmethyl)-1-piperidine ethanol (SL 82.0715) (10 mg/kg). At this time, most of the radioactivity (80%) present in the brain comigrated with authentic [3H]ifenprodil. When administered 30 min before the radiotracer, several sigma ligands inhibited in vivo [3H]ifenprodil binding to the mouse brain with the following rank order of potency (ID50, mg/kg, i.p.): haloperidol (0.27) greater than ifenprodil (0.83) greater than SL 82.0715 (1.37) greater than BMY 14,802 (5.5) greater than 1,3-di-O-tolylguanidine (18). GBR 12909 (20 mg/kg, i.p.) and phencyclidine (30 mg/kg, i.p.) also inhibited this binding by 71 and 59%, respectively. In contrast, the N-methyl-D-aspartate receptor channel blockers 1 [1-(2-thienyl)cyclohexyl] piperidine and MK-801 (10 mg/kg, i.p.) failed to affect [3H]ifenprodil binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310742 TI - 2-[(2-pyridylmethyl)sulfinyl]-1H-thieno[3,4-d]imidazoles. A novel class of gastric H+/K(+)-ATPase inhibitors. AB - 2-[(2-Pyridylmethyl)sulfinyl]thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The [3,4-d] isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo. Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thieno[3,4-d]imidazole lead to highly active compounds with a favorable chemical stability. Various substitution patterns in the thieno[3,4-d]imidazole moiety result in lower biological activity. The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation. Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K(+)-ATPase blocker introduced on the market. PMID- 1310743 TI - New kappa-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus. AB - The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]-2- [(alkylamino)methyl]piperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]- 2-[[1-(3 oxopyrrolidinyl)]methyl]piperidine (10) possesses high activity in the rabbit vas deferens (LVD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antinociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg, sc). The spirocyclic analogue 8-[(3,4 dichlorophenyl)acetyl]-7-(1-pyrrolidinylmethyl)-1,4-dio xa-8- azaspirol4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes. PMID- 1310744 TI - Synthesis, antiproliferative, and antiviral activity of certain 4 aminopyrrolo[2,3-d]pyridazine nucleosides: an entry into a novel series of adenosine analogues. AB - The preparation of novel heterocyclic base modified adenosine analogues, the 4 aminopyrrolo[2,3-d]pyridazine nucleosides, is described. Crucial to their successful preparation was the use of the pyrrole glycoside intermediates 3-cyano 2-formyl-1-(2,3,5-tri-O-benzyl-beta-D-ribofuranosyl)pyrrole (11) and 3-cyano-2 formyl-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)pyrrole (17). Treatment of 11 and 17 with hydrazine dihydrochloride followed by treatment with boron trichloride provided 4-amino-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazine (2) and 4-amino-1-beta-D-arabinofuranosylpyrrolo[2,3-d]pyridazine (3), respectively. 4-Amino-3-bromo-1-beta-D-ribofuranosylpyrrolo[2,3-d]-pyridazine (4) was prepared by a bromination of 4-amino-1-(2,3,5-tri-O-benzyl-beta-D ribofuranosyl)pyrrolo[2,3-d]pyri daz ine (12) and subsequent removal of the benzyl groups with boron trichloride. Compounds 2-4 were evaluated for antiproliferative and antiviral activity. The tubercidin analogue (2) and its arabinosyl derivative (3) were virtually inactive in all assays. In contrast, the 3-bromo analogue 4 inhibited growth of L1210 and H. Ep. 2 cells. Compound 4 was also active against human cytomegalovirus and herpes simplex virus type 1, but the antiviral activity was not completely separated from cytotoxicity. PMID- 1310745 TI - Mechanism of initiation of transcription by Bacillus subtilis RNA polymerase at several promoters. AB - The behavior of the major vegetative cell RNA polymerase of Bacillus subtilis, E sigma A, during initiation of transcription was compared to that of its Escherichia coli counterpart, E sigma 70, at several promoters known to be actively transcribed by both RNA polymerases. Challenge experiments using heparin, restriction endonucleases, and competing promoter DNA under various conditions showed that, at several promoters, complexes with B. subtilis RNA polymerase formed in the absence of nucleoside triphosphates were unstable. These complexes produced DNase I footprints that were less extended than those produced by the E. coli enzyme at the same promoters. Further, in the presence of certain combinations of nucleoside triphosphates, conditions that allow production of abortive oligonucleotides, these B. subtilis RNA polymerase complexes remained dissociable. Thus, at these promoters, the B. subtilis enzyme interacted with the DNA and reached a catalytically active initial transcribing complex without becoming committed to the template. At these same promoters, E. coli RNA polymerase formed stable open complexes before forming any phosphodiester bonds. B. subtilis initial transcribing complexes also remained sensitive to the drug rifampicin until a later stage in the initiation process than did the corresponding E. coli complexes. At one promoter, B. subtilis E sigma A and E. coli E sigma 70 behaved similarly, forming stable open complexes in the absence of any nucleoside triphosphates. PMID- 1310747 TI - Significant effect of adjuvant chemotherapy on survival in locally advanced non small-cell lung carcinoma. PMID- 1310746 TI - Secondary screening system for preclinical testing of human lung cancer therapies. AB - The National Cancer Institute has instituted a primary screening system for testing new agents against cultured cancer cell lines. The purpose of this study was to determine the feasibility of using a nude rat orthotopic (organ-specific) human lung cancer model system as an in vivo secondary screen for general evaluation of new anticancer agents and therapies active against lung cancer. To make this determination, we tested whether this system allows measurement of uptake and tumoricidal activity of anticancer therapies. Tumor-bearing lungs from 53 Rowett nude rats with orthotopically implanted human large-cell undifferentiated lung carcinoma (NCI-H460) were perfused ex vivo for 1 hour with or without each of two anticancer modalities. Lungs were perfused with blood-free perfusate alone (untreated control), perfusate with 100 micrograms/mL doxorubicin (treated positive control), or perfusate with lymphokine-activated killer cells plus human recombinant interleukin-2 (LAK/rIL-2). Weight gain during perfusion was the criterion used to quantitate lung injury. Treatment efficacy was measured by clonogenic assay after enzymatic disaggregation of the perfused tumors. Doxorubicin levels in the tumor and in the uninvolved lung were measured by high performance liquid chromatography. Both treatment groups showed only slight increases in lung weight compared with that in the untreated control group, suggesting good lung tolerance of the procedure. Lung and tumor levels of doxorubicin were 320 +/- 21 ng/mg of tissue and 32 +/- 5 ng/mg of tissue (means +/- SE), respectively. Clonogenic assay demonstrated a fivefold to 10-fold reduction in the surviving fraction of tumor cells with doxorubicin but no change with LAK/rIL-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310748 TI - Phase I trial of granulocyte-macrophage colony-stimulating factor with high-dose cisplatin and etoposide for treatment of small-cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. PMID- 1310749 TI - States begin CDC-sponsored breast and cervical cancer screening. PMID- 1310750 TI - Simian virus 40 large T antigen: the puzzle, the pieces, and the emerging picture. PMID- 1310751 TI - Altered phosphorylation of free and bound forms of monkey p53 and simian virus 40 large T antigen during lytic infection. AB - We have identified the phosphorylation sites in monkey p53 as well as specific changes in the phosphorylation state of free and complexed forms of simian virus 40 (SV40) large T antigen (T) and monkey p53 isolate from SV40 lytically infected CV1 cells. Phosphopeptide analyses of free T and p53 (To and p53o) and complexed T and p53 (T+ and p53+) fractions indicated several quantitative increases in the specific phosphorylation of complexed forms of both proteins. The N terminus of monkey p53+ is phosphorylated at Ser-9, Ser-15, Ser-20, either Ser-33 or Ser-37, and at least one of Ser-90 to Ser-99. The C-terminal sites are Ser-315 and Ser 392. On comparing p53+ with p53o, we found that labeling of the two N-terminal phosphotryptic peptides encompassing residues 1 to 20 and 33 to 101 was increased fivefold and that Ser-315 was sevenfold more labeled than was Ser-392. When T+ was compared with To, the N-terminal peptide containing phosphorylation sites Ser 106 through Thr-124 was twofold more labeled, the peptide containing Ser-657 through Ser-679 was sixfold more labeled and contained up to four phosphorylated serine residues, and Ser-639 and Thr-701 appeared unchanged. Overall, T+ molecules appeared to contain 3.5 mol more of labeled phosphate than did To, with the N-terminal peptide appearing fully phosphorylated. The phosphopeptide patterns obtained for lytic T+ and To fractions were nearly identical to those found for wild-type SV40 T (stably complexed with mouse p53) and mutant 5080 T (defective for p53 binding) expressed in transformed C3H10T1/2 cells (L. Tack, C. Cartwright, J. Wright, A. Srinivasan, W. Eckhart, K. Peden, and J. Pipas, J. Virol. 63:3362-3367, 1989). These results indicate that increases in specific phosphorylation sites in both T+ and p53+ correlate with the association of T with p53. The enhanced phosphorylation state may be a consequence of complex formation between T and p53 or reflect an increased affinity of p53 for highly phosphorylated forms of T. PMID- 1310752 TI - Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocytes. AB - Binding of the retinoblastoma gene product (pRB) by viral oncoproteins, including the E7 of human papillomavirus type 16 (HPV 16), is thought to be important in transformation of cells. One of the steps in transformation is the immortalization process. Here we show that mutations in E7 within the full-length genome which inhibit binding of pRB do not abrogate the ability of the HPV 16 DNA to immortalize primary human epithelial (keratinocyte) cells. A mutation in one of the cysteines of a Cys-X-X-Cys motif which is contained in the carboxy half of the E7 and is part of a zinc finger arrangement completely eliminates the ability of HPV 16 DNA to immortalize cells. The results indicate the importance of E7 in the immortalization of primary keratinocytes but suggest that the binding of pRB is not essential. PMID- 1310754 TI - Recombinant fowlpox viruses expressing the glycoprotein B homolog and the pp38 gene of Marek's disease virus. AB - Two Marek's disease virus (MDV) genes, one homologous to the glycoprotein B gene of herpes simplex virus and encoding the B antigen complex and the other encoding a 38-kDa phosphorylated protein (pp38), were inserted into the fowlpox virus (FPV) genome under the control of poxvirus promoters. Randomly selected nonessential regions of FPV were used for insertion, and the vaccinia virus 7.5 kDa polypeptide gene promoter or a poxvirus synthetic promoter was used for expression of MDV genes. Gene expression in cells infected with these recombinants was highly influenced by the promoter (the synthetic promoter being more effective) but was only slightly influenced by the insertion site and by the transcription direction of the insert relative to the direction of the flanking FPV sequences. Cells infected with an FPV recombinant expressing the MDV gB gene reacted positively with a monoclonal antibody specific to this glycoprotein in an immunofluorescence assay. Immunoprecipitation of infected cell lysates showed three glycoproteins identical to those associated with the B antigen complex of MDV (100, 60, and 49 kDa). Cells infected with a recombinant expressing the pp38 gene reacted positively with an anti-pp38 monoclonal antibody in an immunofluorescence assay. The generated protein was phosphorylated and had a molecular weight similar to that of the native pp38 protein. Sera from chickens immunized with an FPV recombinant expressing the MDV glycoprotein B gene reacted with MDV-infected cells. PMID- 1310753 TI - Unusually high frequency of reconstitution of long terminal repeats in U3-minus retrovirus vectors by DNA recombination or gene conversion. AB - Recently, we described a retrovirus vector system with which to study formation of cDNA genes (R. Dornburg and H. M. Temin, Mol. Cell. Biol. 6:2328-2334, 1988; Mol. Cell. Biol. 8:64-72, 1990; J. Virol. 64:886-889, 1990). For these studies, retrovirus vectors were constructed in which the U3 region of the 3' long terminal repeat (LTR) was deleted. After one round of retrovirus replication, such vectors formed a provirus with two U3-minus LTRs. However, the insertion of some additional sequences into such vectors promoted vector rearrangements with an efficiency greater than 95%. Such rearranged vectors behaved like vectors with two wild-type LTRs. Proviruses derived from such vectors were investigated by Southern blot analysis, polymerase chain reaction, and DNA sequencing. We found that the U3 region was reconstituted, resulting in vectors with LTRs like wild type virus. The sequences that reconstituted the U3 region of the vector LTR were derived from LTR sequences present in the helper cell. Since no retroviral protein coding sequences were detected in infected target cells, recombination of vector sequences with coencapsidated helper cell sequences during reverse transcription seems very unlikely. Thus, it appears that the recombination (or gene conversion) events leading to a vector with reconstituted LTRs occurred at the DNA level. The high frequency of this recombination (or gene conversion) was dependent on internal vector sequences. PMID- 1310755 TI - Protection against Marek's disease by a fowlpox virus recombinant expressing the glycoprotein B of Marek's disease virus. AB - Fowlpox virus (FPV) recombinants expressing the glycoprotein B and the phosphorylated protein (pp38) of the GA strain of Marek's disease virus (MDV) were assayed for their ability to protect chickens against challenge with virulent MDV. The recombinant FPV expressing the glycoprotein B gene elicited neutralizing antibodies against MDV, significantly reduced the level of cell associated viremia, and, similar to the conventional herpesvirus of turkeys, protected chickens against challenge with the GA strain and the highly virulent RB1B and Md5 strains of MDV. The recombinant FPV expressing the pp38 gene failed to either elicit neutralizing antibodies against MDV or protect the vaccinated chickens against challenge with MDV. PMID- 1310756 TI - Expression of processed envelope protein of hepatitis C virus in mammalian and insect cells. AB - The putative envelope protein of hepatitis C virus (HCV) was expressed in insect cells by using a baculovirus expression vector and in monkey COS cells under the control of exogenous promoters. The expressed envelope proteins, identified by immunoblot analysis using sera from patients with chronic HCV infection, were a series of glycoproteins of 35 to 24 kDa (gp35-24) in insect cells and a single species of glycoprotein of 35 kDa (gp35) in monkey cells. The size difference of these proteins was due to the different degrees of glycosylation. The envelope proteins expressed in these cells were produced by common specific cleavage from the precursor protein, and cleavage positions of the envelope protein were mapped at about amino acids 190 and 380. The gp35-24 proteins expressed in insect cells were used for detection of antibody against HCV envelope protein in patient sera. The results showed that (i) the antibody is detected in 2 to 17% of various patients with hepatitis C, (ii) three patients were apparently cured after acquiring the antienvelope antibody, and (iii) in sera of patients with more than a 20-year history of infection, the antibody sometimes coexisted with HCV. These results suggest that the antienvelope antibody is neutralizing only in limited number of patients with hepatitis C. PMID- 1310757 TI - Highly efficient focus formation by Rous sarcoma virus on adenovirus type 12 E1A transformed rat 3Y1 cells. AB - When rat 3Y1 cells were infected with Rous sarcoma virus (RSV) variant SR-RSV D(H), many 3Y1 cells acquired a stable provirus but only few of them formed transformed foci. In contrast, 12E1AY cells (3Y1 cells expressing the adenovirus type 12 [Ad12] E1A protein) formed transformed foci upon RSV infection with the same high frequency as did chicken embryo fibroblast cells. This enhancement of focus-forming efficiency was specifically observed in 3Y1 cells expressing Ad12 E1A protein but was not observed in 3Y1 cells expressing simian virus 40 T, c myc, p53, c-fos, or v-fos protein. This enhancement was not evident in 5E1AY cells (3Y1 cells expressing the Ad5 E1A protein). Judging from the experiment using Ad12-Ad5 hybird E1A DNAs, the N-terminal half of the Ad12 E1A protein was responsible for this enhancement. The promoter activity of the RSV long terminal repeat measured by pLTR-CAT did not correlate to the efficiency of focus formation by RSV in these 3Y1 cells. Moreover, RSV containing the neo gene instead of the src gene produced G418-resistant cells equally efficiently among 3Y1, E1AY, and chicken embryo fibroblast cells. These results suggest that the enhancement of focus formation by RSV is not due to the increased expression of the src gene by the E1A protein. src mRNA and src protein were lower in RSV transformed E1AY (RSVE1AY) cells than in RSV-transformed 3Y1 (RSV3Y1) cells. The phosphotyrosine-containing proteins were also less abundant in RSVE1AY cells than in RSV3Y1 cells, suggesting that E1AY cells require a lower threshold dose of p60v-src for transformation than do 3Y1 cells. E1AY cells were found to be more sensitive to lysis by detergents. The results suggest that the enhancement is due to changes in membrane structures in E1AY cells. PMID- 1310758 TI - Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic, and polytropic murine leukemia viruses. AB - The envelope glycoproteins (SU) of mammalian type C retroviruses possess an amino terminal domain of about 200 residues, which is involved in binding a cell surface receptor. In this domain, highly conserved amino acid sequences are interrupted by two segments of variable length and sequence, VRA and VRB. We have studied the role of these variable regions in receptor recognition and binding by constructing chimeric molecules in which portions of the amino-terminal domains from amphotropic (4070A), xenotropic (NZB), and polytropic (MCF 247) murine leukemia virus SU proteins were permuted. These chimeras, which exchanged either one or two variable regions, were expressed at the surface of replication defective viral particles by a pseudotyping assay. Wild-type or recombinant env genes were transfected into a cell line producing Moloney murine leukemia virus particles devoid of envelope glycoproteins in which a retrovirus vector genome carrying an Escherichia coli lacZ gene was packaged. The host range and sensitivity to interference of pseudotyped virions were assayed, and we observed which permutations resulted in receptor switch or loss of function. Our results indicate that the determinants of receptor choice are found within the just 120 amino acids of SU proteins. Downstream sequences contribute to the stabilization of the receptor-specific structure. PMID- 1310760 TI - Decline in CD4+ cell numbers in cats with naturally acquired feline immunodeficiency virus infection. AB - T-cell subsets were studied by fluorescence-activated cell sorter analysis in 57 feline immunodeficiency virus (FIV)-seropositive cats with naturally acquired FIV infection to see whether CD4(+)-CD8+ alterations were comparable to those observed in human immunodeficiency virus-infected patients. CD4+ values were decreased and CD8+ values were increased. The CD4+/CD8+ ratio was reduced to 1.6, compared with 3.3 in 33 FIV-seronegative control cats. Variance analysis of data showed a significant influence of FIV seropositivity, sex, and spaying of female cats on CD4+ values. CD8+ values were significantly influenced by FIV seropositivity, age, and breed. These findings indicate a similarity between FIV and human immunodeficiency virus infections, as far as alterations of T-cell subsets are concerned. PMID- 1310759 TI - Internal ribosome entry site within hepatitis C virus RNA. AB - The mechanism of initiation of translation on hepatitis C virus (HCV) RNA was investigated in vitro. HCV RNA was transcribed from the cDNA that corresponded to nucleotide positions 9 to 1772 of the genome by using phage T7 RNA polymerase. Both capped and uncapped RNAs thus transcribed were active as mRNAs in a cell free protein synthesis system with lysates prepared from HeLa S3 cells or rabbit reticulocytes, and the translation products were detected by anti-gp35 antibodies. The data indicate that protein synthesis starts at the fourth AUG, which was the initiator AUG at position 333 of the HCV RNA used in this study. Efficiency of translation of the capped methylated RNA appeared to be similar to that of the capped unmethylated RNA. However, a capped methylated RNA showed a much higher activity as mRNA than did the capped unmethylated RNA in rabbit reticulocyte lysates when the RNA lacked a nucleotide sequence upstream of position 267. The results strongly suggest that HCV RNA carries an internal ribosome entry site (IRES). Artificial mono- and dicistronic mRNAs were prepared and used to identify the region that carried the IRES. The results indicate that the sequence between nucleotide positions 101 and 332 in the 5' untranslated region of HCV RNA plays an important role in efficient translation. Our data suggest that the IRES resides in this region of the RNA. Furthermore, an IRES in the group II HCV RNA was found to be more efficient than that in the group I HCV RNA. PMID- 1310761 TI - Involvement of simian virus 40 (SV40) small t antigen in trans activation of SV40 early and late promoters. AB - We have previously found that simian virus 40 (SV40) small t antigen (small t) can trans activate the E2A and VA-I genes of adenovirus in plasmid DNA transfected cells (M. R. Loeken, I. Bikel, D. M. Livingston, and J. Brady, Cell 55:1171-1177, 1988). To determine whether trans activation by small t might be involved in the SV40 productive infection cycle, we examined the effects of cotransfecting plasmids encoding small t with plasmids containing the chloramphenicol acetyltransferase (CAT) gene linked to the SV40 early or late promoter. Small t increased three- to fivefold the expression of a CAT plasmid linked to the SV40 early promoter and enhancer. Small t expression had no effect by itself on CAT activity directed by the SV40 late promoter, but small t enhanced the effect of a suboptimal concentration of a plasmid expressing large T up to 10-fold. When the concentration of the plasmid expressing large T was increased to a level at which large T alone stimulated the late promoter ninefold, the enhancement by small t was only twofold. The effects of small t on both the SV40 early and late promoters depended on sequences within the small t unique domain, since a plasmid expressing only the first 82 amino acids common to both large T and small t was inactive. The effects of small t on early- and late promoter-directed CAT enzyme activity was reflected in increased CAT mRNA as measured by S1 analysis. These results suggest that SV40 small t may play a role in viral infection by increasing transcription from the early promoter and from the late promoter at times when large T levels are low. PMID- 1310762 TI - Functions of the sequences at the ends of the inverted repeats of pseudorabies virus. AB - Two mutants were constructed to explore the functions of the sequences at the end of the S terminus of pseudorabies virus (PrV). In mutant vYa, 17 bp from the internal inverted repeat, as well as adjacent sequences from the L component, were deleted. In mutant v135/9, 143 bp from the internal inverted repeat (including sequences with homology to the pac-1 site of herpes simplex virus), as well as adjacent sequences from the L component, were deleted. Our aim in constructing these mutants was to ascertain whether equalization of the terminal regions of the S component would occur, whether genome termini that lack either the terminal 17 or 143 bp would be generated as a result of equalization of the repeats (thereby identifying the terminal nucleotides that may include cleavage signals), and whether inversion of the S component would occur (thereby ascertaining the importance of the deleted sequences in this process). The results obtained show the following (i) The removal of the terminal 17 or 143 bp of the internal S component, including the sequences with homology to the pac-1 site, does not affect the inversion of the Us. (ii) The equalization of both the vYa and the v135/9 inverted repeats occurs at high frequency, the terminal repeats being converted and becoming similar to the mutated internal inverted repeat. (iii) Mutants in which the 17 terminal base pairs (vYa) have been replaced by unrelated sequences are viable. However, the 143 terminal base pairs appear to be essential to virus survival; concatemeric v135/9 DNA with equalized, mutant-type, inverted repeats accumulates, but mature virions with such equalized repeats are not generated at high frequency. Since concatemeric DNA missing the 143 bp at both ends of the S component is not cleaved, the terminal 143 bp that include the sequences with homology to the pac-1 site are necessary for efficient cleavage. (iv) v135/9 intracellular DNA is composed mainly of arrays in which one S component (with two equalized inverted repeats both having the deletion) is bracketed by two L components in opposite orientations and in which two L components are in head-to-head alignment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310763 TI - Association of heat shock protein 70 with enterovirus capsid precursor P1 in infected human cells. AB - Members of the human heat shock (HSP) family of related proteins are involved in the intracellular folding, transport, and assembly of proteins and protein complexes. We have observed that human heat shock protein 70 (HSP70) is associated with the capsid precursor P1 of poliovirus and coxsackievirus B1 in infected HeLa cells. Antiserum generated against HSP70 coimmunoprecipitated the poliovirus protein P1, an intermediate in capsid assembly. Similarly, alpha virion serum coimmunoprecipitated HSP70 from virus-infected cell extracts, but not from mock-infected cell extracts. The HSP70-P1 complex was stable in high salt medium but was sensitive to incubation with 2 mM ATP, which is a characteristic of other known functional complexes between HSP70 and cellular proteins. The P1 in the complex was predominantly newly synthesized, and the half life of complexed P1 was nearly twice as long as that of total P1. The HSP70-P1 complex was found to sediment at 3S to 6S, suggesting that it may be part of, or a precursor to, the "5S promoter particles" thought to be an assembly intermediate of picornaviruses. The finding that HSP70 was associated with the capsid precursors of at least two enteroviruses may suggest a functional role of these complexes in the viral life cycles. PMID- 1310764 TI - Functional interactions between the fusion protein and hemagglutinin neuraminidase of human parainfluenza viruses. AB - The fusion glycoprotein (F) and hemagglutinin-neuraminidase (HN) genes of human parainfluenza virus type 2 (PI2) were molecularly cloned and expressed in HeLa-T4 cells by using the vaccinia virus-T7 transient expression system. Expression of the F and HN proteins was detected by using immunoprecipitation and surface immunofluorescence staining. Although the F protein was found to be cleaved into F1 and F2 and expressed on cell surfaces, no cell fusion was observed. However, cotransfection of the F-protein gene together with the P12 HN gene resulted in significant levels of cell fusion. Cell fusion was also observed when separate cell cultures were transfected with the HN and F genes and the F-expressing cells were mixed with the HN-expressing cells. Surprisingly, when the PI2 F protein was expressed together with the parainfluenza virus type 3 (PI3) HN protein, no fusion was detectable in the transfected cells. Similarly, no fusion was found upon coexpression of the PI2 HN and PI3 F proteins. However, coexpression of the PI3 F and HN proteins resulted in extensive cell fusion, which resembled the PI2 coexpression result. These results indicate that under the conditions used, the F protein is unable to cause fusion by itself and the HN protein provides a specific function in cell fusion which cannot be provided by another paramyxovirus attachment protein. Further, the results suggest that a type specific functional interaction between the F and HN proteins is involved in mediating cell fusion. PMID- 1310765 TI - A 10-base-pair element of the human immunodeficiency virus type 1 long terminal repeat (LTR) is an absolute requirement for transactivation by the human cytomegalovirus 72-kilodalton IE1 protein but can be compensated for by other LTR regions in transactivation by the 80-kilodalton IE2 protein. AB - Transient gene expression studies have indicated that human cytomegalovirus (HCMV) specifically transactivates the human immunodeficiency virus (HIV) long terminal repeat (LTR). We show here, by a specific mutational analysis, that only the TATA box region is obligatory for transactivation of the HIV-1 LTR by HCMV. Similarly, this element is also sufficient for transactivation by either the HCMV 72-kDa major immediate-early 1 (IE1) or 80-kDa IE2 gene product independently. However, deletion of a 10-bp region from the minimal responsive element, 5' to the TATA box, dramatically reduced the level of HCMV 72-kDa IE1 or 80-kDa IE2 transactivation, indicating a crucial role for this element in transactivation. Whereas inclusion of the TAR element or Sp1 sites on this 10-bp-deleted minimal promoter had no effect on the removal of IE1 transactivation, TAR and Sp1 elements did compensate for the 10-bp element in transactivation by IE2 and HCMV. Consequently, the sequence requirements of the HIV-1 LTR for transactivation by HCMV can be reproduced by these IE1 and IE2 gene products of HCMV. PMID- 1310766 TI - Identification and characterization of a human herpesvirus 6 gene segment that trans activates the human immunodeficiency virus type 1 promoter. AB - Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus, and in vitro, HHV-6 can productively infect many of the same cell types as can human immunodeficiency virus (HIV). Coinfection by both viruses in vitro can lead to both activation of the HIV promoter and acceleration of cytopathic effects. We have previously demonstrated that a large, 22.25-kb cloned HHV-6 fragment, pZVB70, can trans activate HIV promoter expression in vitro. In this study, we show that the pZVB70 fragment can trans activate the HIV promoter in human T-cell lines as well as in the monkey kidney cell line CV-1. The pZVB70 insert was digested with various restriction enzymes, and individual fragments were transfected into cells to test for their ability to trans activate the HIV promoter. By this method, we have identified a 1.8-kb subfragment, B701, that is involved in trans activation. Sequence analyses show that B701 potentially encodes a 143-amino-acid protein. This protein shares no homology with other herpesvirus proteins, such as ICP0 and ICP4, that have been shown to trans activate the HIV promoter. However, it shows weak sequence homology with the gene products encoded by the cytomegalovirus early US22 gene family, suggesting that the putative B701 protein may be an HHV-6 early regulatory protein. The 143-amino-acid coding sequence of B701 was cloned by polymerase chain reaction, and transfection of this construct into cells activated HIV promoter expression. The target site on the HIV promoter for the putative B701 protein is mapped to the NF-kappa B binding site. Our results suggest that the putative B701 protein may function by directly binding to the NF kappa B site or may involve cellular factors, such as NF-kappa B, either directly or indirectly. PMID- 1310767 TI - Insertion of the human immunodeficiency virus CD4 receptor into the envelope of vesicular stomatitis virus particles. AB - Enveloped virus particles carrying the human immunodeficiency virus (HIV) CD4 receptor may potentially be employed in a targeted antiviral approach. The mechanisms for efficient insertion and the requirements for the functionality of foreign glycoproteins within viral envelopes, however, have not been elucidated. Conditions for efficient insertion of foreign glycoproteins into the vesicular stomatitis virus (VSV) envelope were first established by inserting the wild-type envelope glycoprotein (G) of VSV expressed by a vaccinia virus recombinant. To determine whether the transmembrane and cytoplasmic portions of the VSV G protein were required for insertion of the HIV receptor, a chimeric CD4/G glycoprotein gene was constructed and a vaccinia virus recombinant which expresses the fused CD4/G gene was isolated. The chimeric CD4/G protein was functional as shown in a syncytium-forming assay in HeLa cells as demonstrated by coexpression with a vaccinia virus recombinant expressing the HIV envelope protein. The CD4/G protein was efficiently inserted into the envelope of VSV, and the virus particles retained their infectivity even after specific immunoprecipitation experiments with monoclonal anti-CD4 antibodies. Expression of the normal CD4 protein also led to insertion of the receptor into the envelope of VSV particles. The efficiency of CD4 insertion was similar to that of CD4/G, with approximately 60 molecules of CD4/G or CD4 per virus particle compared with 1,200 molecules of VSV G protein. Considering that (i) the amount of VSV G protein in the cell extract was fivefold higher than for either CD4 or CD4/G and (ii) VSV G protein is inserted as a trimer (CD4 is a monomer), the insertion of VSV G protein was not significantly preferred over CD4 or CD4/G, if at all. We conclude that the efficiency of CD4 or CD4/G insertion appears dependent on the concentration of the glycoprotein rather than on specific selection of these glycoproteins during viral assembly. PMID- 1310768 TI - Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation. AB - The nucleotide sequence of the 5' nontranslated region of encephalomyocarditis virus (EMCV-Rueckert) was determined, and a consensus RNA structural model for this sequence (850 bases) and three other poly(C)-containing cardioviruses (mengovirus, EMCV-B, and EMCV-D) was created through reiterative use of a minimum free-energy folding algorithm. The RNA elements within this region which contribute to translation of EMCV proteins were mapped in cell-free reactions programmed with cDNA-derived RNA transcripts. The data provide evidence that stem loop motifs I, J and K, formed by viral bases 451 to 785, are important components of cap-independent translation. In contrast to other reports, a minimal role for stem-loop H (bases 406 to 444) in translational activity is indicated. Small 5' nontranslated region fragments (bases 667 to 797) containing the J and K motifs proved strong competitive inhibitors when added to cell-free reactions programmed with exogenous capped or uncapped mRNAs. The putative sequestering of required translational factors by this segment clearly contributes to translational activity, but also suggests a possible competitive mechanism for the down regulation of host protein synthesis during viral infection. PMID- 1310770 TI - Folding and processing of the capsid protein precursor P1 is kinetically retarded in neutralization site 3B mutants of poliovirus. AB - Poliovirus mutants in neutralizing antigenic site 3B were constructed by replacing the glutamic acid residue at amino acid 74 of capsid protein VP2 (VP2074E), using site-specific mutagenesis methods. All viable mutants display small-plaque phenotypes. Characterization of these mutants indicates that capsid assembly is perturbed. Although the defect in capsid assembly reduces the yield of mutant virus particles per cell, the resultant assembled particle is wild-type like in structure and infectivity. Analyses of capsid assembly intermediates show a transient accumulation of the unprocessed capsid protein precursor, P1, indicating that cleavage of the mutant P1 by the 3CD protease is retarded. The mutant VP0-VP3-VP1 complex generated upon P1 cleavage appears assembly competent, forming pentamer and empty capsid assembly intermediates and infectious virion particles. Although the structure of the infectious mutant virus is virtually identical with that of the wild-type virus, the thermal stability of the mutant virus is dramatically increased over that of the wild-type virus. Thus, mutations at this residue are pleiotropic, altering the kinetics of capsid assembly and generating a virus that is more thermostable and more resistant to neutralization by the site 3B monoclonal antibodies. PMID- 1310769 TI - Human CD8+ herpes simplex virus-specific cytotoxic T-lymphocyte clones recognize diverse virion protein antigens. AB - The role of the HLA class I-restricted, CD8+, herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTL) in the control of human HSV infections is controversial because previous reports suggest that a substantial portion of the antigen-specific lytic response is mediated by CD4+ cells. To address this question directly, we isolated HSV-specific CD8+ CTL clones from a patient with recurrent genital herpes. These CTL were cloned by coculturing responder peripheral blood mononuclear cells (PBMC) with phytohemagglutinin-stimulated PBMC that had been infected with live HSV-2 and then irradiated prior to the addition of responder cells. After 1 week, CTL were cloned by limiting dilution using phytohemagglutinin stimulation and allogeneic feeder PBMC. Seven clones were isolated; all seven clones were CD8+ CD4- CD3+ DRbright, six lysed only HSV-2 infected targets, and one lysed both HSV-1- and HSV-2-infected targets. Antigen presentation was restricted by two to three different HLA class I loci. To determine the antigens recognized by these HSV-specific CTL, target cells were infected with HSV in the presence of acyclovir, 5,6-dichloro-1-beta-D ribofuranosylbenzimidazole, or cycloheximide in a series of drug block/release protocols to limit the repertoire of viral gene expression to select transcriptional classes. Five of the clones exhibited a different pattern of cytotoxicity, suggesting that each recognized a distinct HSV antigen. One of the clones appears to be directed against an immediate-early antigen; six of the clones recognize virion proteins. Five of these clones recognized internal virion proteins that could be introduced into target cells by HSV infection in the absence of virus gene expression. Antigen specificity was further tested by using vaccinia virus vectors that express glycoproteins gD2 and gB2 or the tegument protein VP16. One clone lysed vaccinia virus/gD2-infected target cells; the remaining clones did not recognize any of these gene products. The diversity of the CD8+ response from a single individual indicated that several different antigens are recognized when presented in the context of a variety of class I HLA alleles, a pattern that markedly differs from that described for another human herpesvirus, cytomegalovirus. PMID- 1310772 TI - Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis. AB - A series of genetic deletions based partly on two RNA secondary structure models (M. A. Skinner, V. R. Racaniello, G. Dunn, J. Cooper, P. D. Minor, and J. W. Almond, J. Mol. Biol. 207:379-392, 1989; E. V. Pilipenko, V. M. Blinov, L. I. Romanova, A. N. Sinyakov, S. V. Maslova, and V. I. Agol, Virology 168:201-209, 1989) was made in the cDNA encoding the 5' noncoding region (5' NCR) of the poliovirus genome in order to study the sequences that direct the internal entry of ribosomes. The modified cDNAs were placed between two open reading frames in a single transcriptional unit and used to transfect cells in culture. Internal entry of ribosomes was detected by measuring translation from the second open reading frame in the bicistronic mRNA. When assayed alone, a large proportion of the poliovirus 5' NCR superstructure including several well-defined stem-loops was required for ribosome entry and efficient translation. However, in cells cotransfected with a complete infectious poliovirus cDNA, the requirement for the stem-loops in this large superstructure was reduced. The results suggest that virus infection modifies the cellular translational machinery, so that shortened forms of the 5' NCR are sufficient for cap-independent translation, and that the internal entry of ribosomes occurs by two distinct modes during the virus replication cycle. PMID- 1310771 TI - Identification of three transforming proteins encoded by cottontail rabbit papillomavirus. AB - Cottontail rabbit papillomavirus (CRPV) provides an animal model for human papillomaviruses associated with a high risk of cancer development. So far, nothing is known about the transforming functions of CRPV genes because of the lack of an assay system. We have recently developed two systems to assay for CRPV transforming functions. One is based on the finding that transformation of NIH 3T3 cells by CRPV is considerably increased by deleting sequences in open reading frame L2. The second one is based on the use of a cottontail rabbit skin epithelial cell line, sf1Ep (C. Meyers and F. O. Wettstein, Virology 181:637-646, 1991). Mutations were introduced which abolished expression of the full-length E6 protein (LE6), the short E6 protein (SE6) initiated at the second ATG of E6, the E7 protein, or the E5 protein. Mutations affecting LE6 or E7, but not SE6, reduced transformation of NIH 3T3 and sf1Ep cells. Transformed NIH 3T3 cell lines with mutations in LE6 and E7 did not grow in soft agar, while those with mutations in SE6 and E5 grew with a reduced efficiency. The cell lines with mutations in LE6, SE6, or E7 still did induce tumors in nude mice. These mutations, however, abolished the ability to induce papillomas in rabbits. When expressed individually with a retroviral vector, LE6, SE6, or E7, but not E5, conferred anchorage-independent growth. The level of viral protein expression in these cell lines was generally low, and a comparison of the abundance of virus specific mRNA showed that cell lines contained 20 to 50 times less mRNA than a cottontail rabbit papilloma. These data demonstrate that CRPV encodes at least three transforming proteins. PMID- 1310773 TI - ART-CH, a new chicken retroviruslike element. AB - A 3' region of a previously unknown retroviruslike element named ART-CH (avian retrotransposon from chicken genome) was obtained in the course of polymerase chain reaction-mediated cloning of avian leukosis virus long terminal repeats (LTRs) from DNAs of infected chicken cells. About 50 copies of ART-CH are present in the genome of chickens of different breeds. ART-CH is not found in DNA of quails, ducks, turkeys, or several other birds tested. The ART-CH element is about 3 kb in size, including 388 bp LTRs. The major class of ART-CH-specific RNA, also 3 kb in size, is detected in various organs of chickens. An ART-CH polypurine tract, a tRNA(Trp)-binding site, regions around the TATA box and polyadenylation signal, and the beginning of the putative gag gene strongly resemble the corresponding regions of avian leukosis viruses and EAV, the two described classes of chicken retroviruses. An open reading frame capable of encoding a polypeptide with a putative transmembrane domain is located upstream of the right ART-CH LTR. This sequence, as well as the U3 and U5 regions of the ART-CH LTR, has no obvious similarities with the corresponding parts of other known vertebrate retroviruses and retrotransposons. A short sequence upstream of the right LTR of ART-CH is very similar to sequences which flank the 3' ends of the oncogenes v-src, v-myc, v-fps, and v-crk in four different recombinant avian retroviruses and which are absent from the genomes of other studied avian retroviruses. Thus, ART-CH is a new endogenous chicken provirus that may participate in the formation of recombinant oncogenic retroviruses. PMID- 1310775 TI - Effect of zinc ions on the biochemical behavior of simian virus 40 small-t antigen expressed in bacteria. AB - The simian virus 40 small-t antigen contains 10 cysteine residues, 6 of which are organized in two CysXCysXXCys clusters. Mutation of individual Cys residues in the two clusters or mutation of specific residues found between these clusters causes pronounced instability of the protein in animal cells. Protein instability correlates with failure of the bacterially expressed mutant proteins to bind zinc ions, an interaction which allows purification of large amounts of small-t antigen in monomeric form. PMID- 1310774 TI - Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: novel mRNAs and proteins produced by HTLV type I. AB - Novel cytoplasmic mRNA species produced by human T-cell leukemia virus type I (HTLV-I) were cloned by using the polymerase chain reaction technique. Five novel 3' splice sites located in the X region and upstream of the env gene were identified. Splicing to the 3' splice sites in the X region generates mRNAs that express two previously unidentified viral proteins, named Rof and Tof. Tof accumulates in the nucleoli of transfected cells. The other viruses of the HTLV family, such as HTLV-II and bovine leukemia virus, also have a complex splicing pattern and are capable of producing additional proteins encoded in the X region. These results suggest that HTLV-I and other members of the HTLV family produce novel proteins, which may contribute to the biological properties of these viruses. PMID- 1310776 TI - Simian virus 40 large T antigen stably complexes with a 185-kilodalton host protein. AB - Stable interactions between simian virus 40 large T antigen and host proteins are believed to play a major role in the ability of the viral protein to transform cells in culture and induce tumors in vivo. Two of these host proteins, the retinoblastoma susceptibility protein (pRB) and p53, are products of tumor suppressor genes, suggesting that T antigen exerts at least a portion of its transforming activity by complexing with and inactivating the function of these proteins. While analyzing T antigen-host protein complexes in mouse cells, we noted a protein of 185 kDa (p185) which specifically coimmunoprecipitates with T antigen. Coimmunoprecipitation results from the formation of stable complexes between T antigen and p185. Complex formation is independent of the interactions of T antigen with pRB, p120, and p53. Furthermore, analysis of T-antigen mutants suggests that T antigen-p185 complex formation may be important in transformation by simian virus 40. PMID- 1310777 TI - A human cytomegalovirus glycoprotein complex designated gC-II is a major heparin binding component of the envelope. AB - The purposes of this study were to determine whether heparin would block human cytomegalovirus (HCMV) infection of skin fibroblast (SF) cells and to identify HCMV envelope glycoproteins which might have affinity for heparin. It was determined that soluble heparin in concentrations of 5 to 20 micrograms/ml was capable of blocking HCMV infection of SF cells. However, after virus had adsorbed to the SF cells, heparin lost its ability to block infection. It was also determined that treatment of SF cells with heparinase to remove cell surface heparinlike moieties prevented HCMV infection of SF cells. These data showed that HCMV, like other herpesviruses, adsorbed to cells by binding cell surface heparin. Heparin affinity chromatography was done to determine which HCMV envelope glycoproteins bound heparin. HCMV envelope glycoproteins were solubilized in a nonionic detergent and applied to a heparin affinity column. An HCMV glycoprotein complex designated gC-II was the major component to bind to immobilized heparin and elute in the presence of soluble heparin. PMID- 1310778 TI - The parainfluenza virus type 1 P/C gene uses a very efficient GUG codon to start its C' protein. AB - Parainfluenza virus type 1 (PIV1) and Sendai virus (SEN) are very closely related, but the PIV1 P/C gene does not contain the ACG codon which initiates the SEN C' protein. Nevertheless, a protein corresponding to the PIV1 C' protein was observed both in vivo and in vitro. The initiation site of this protein maps upstream of the PIV1 C protein AUG in a region that does not contain an AUG codon. We have used site-directed mutagenesis to demonstrate that the PIV1 C' protein initiates from a GUG codon, four codons upstream of where the ACG is found in SEN. Remarkably, this GUG appears to initiate in vivo almost as frequently as AUG in the same context. However, whereas GUG permits downstream expression of the P and C proteins, AUG in this context does not. The conservation of an upstream non-AUG initiation codon for C' among PIV1 and SEN suggests that it is important for virus replication, even though some paramyxoviruses express only the C protein and others have no C open reading frame at all. PMID- 1310779 TI - A point mutation within a distinct conserved region of the herpes simplex virus DNA polymerase gene confers drug resistance. AB - We have shown that a drug-resistant mutant from a clinical isolate of herpes simplex virus contains a single point mutation in the DNA polymerase gene that confers resistance to both acyclovir and foscarnet. The mutated amino acid is located within a distinct conserved region shared among alpha-like DNA polymerases which we designate region VII. We infer that these conserved sequences are directly or indirectly involved in the recognition and binding of nucleotide and PPi substrates. PMID- 1310780 TI - Herpesvirus saimiri oncogene STP-C488 encodes a phosphoprotein. AB - The STP-C488 open reading frame of herpesvirus saimiri encodes an oncoprotein that has transforming and tumor-inducing activities independent of the rest of the herpesvirus genome. STP-C488 protein has an unusual, membrane-associated, fibrous structure and is located primarily in perinuclear compartments. We now report that STP-C488 is phosphorylated in vivo. The phosphorylated form, which accounted for about 15% of STP-C488 in transformed cells, migrated slightly more slowly through sodium dodecyl sulfate-polyacrylamide gels than unphosphorylated STP-C488. A serine residue near the amino terminus was shown to be the site of phosphorylation. However, phosphorylation was not required for transformation of Rat-1 cells by STP-C488. PMID- 1310781 TI - Processing of avian retroviral gag polyprotein precursors is blocked by a mutation at the NC-PR cleavage site. AB - The avian sarcoma and leukosis viruses (ASLV) encode a protease (PR) at the C terminus of gag which in vivo catalyzes the processing of both gag and gag-pol precursors. The studies reported here were undertaken to determine whether PR is able to cleave these polyproteins while it is still part of the gag precursor or whether the release of its N terminus to form free PR is necessary for full proteolytic activity. To address this question, we created a mutation that disrupts the PR cleavage site between the NC and PR coding regions of the gag gene. This mutation was introduced into a eukaryotic vector that expresses only the gag precursor and into an otherwise infectious clone of ASLV that carries the neo gene as a selectable marker. These constructs were expressed in monkey COS cells or in quail QT35 cells, respectively. Processing was impaired in both systems. Mutant particles were formed, but they contained no mature processed gag proteins. We observed only the uncleaved gag precursor polypeptide Pr76 in one case or Pr76 and a cleaved product of about 60 kDa in the other. Processing of the mutant gag precursor could be complemented in trans by from a wild-type construct, suggesting that the mutation did not induce gross structural alterations in its precursor. Our results suggest that the PR first must be released from its precursor before it can attack other sites in the gag and gag pol polyproteins and that cleavage at the NC-PR boundary is a prerequisite for the initiation of the PR-directed processing. PMID- 1310782 TI - EBNA1 distorts oriP, the Epstein-Barr virus latent replication origin. AB - The Epstein-Barr virus nuclear antigen 1 (EBNA1) protein binds and activates the latent replication origin (oriP) of the Epstein-Barr virus. We have been studying EBNA1 to determine how it activates replication at oriP. Here we demonstrate that upon binding of EBNA1 to oriP, two thymine residues become reactive to potassium permanganate (KMnO4), indicating a helical distortion at these sites. The KMnO4 reactive thymines are 64 bp apart in the region of dyad symmetry of oriP. Dimethyl sulfate protection studies indicated that EBNA1 binds on the opposite face of the helix from the reactive thymines. The nature of the helical distortion induced by EBNA1 and its possible significance to the initiation of replication are discussed. PMID- 1310783 TI - Distinct subsets of retroviruses encode dUTPase. AB - The nonprimate lentiviruses feline immunodeficiency virus, equine infectious anemia virus, visna virus, and caprine encephalitis virus contain a gene segment in the polymerase gene that is lacking in the primate lentiviruses. A related sequence has been noted in other retroviruses, most notably the type D retroviruses. Computer searches have indicated a relatedness between this unique gene segment, termed proteaselike element and elements of both the aspartate proteinase and the dUTPase enzyme families. In this report, we show that members of both nonprimate lentiviruses and type D retroviruses possess dUTPase activity and present a formal demonstration that in feline immunodeficiency virus, the activity is encoded by the proteaselike element. PMID- 1310784 TI - Simian virus 40 (SV40) small t antigen inhibits SV40 DNA replication in vitro. AB - We describe a biochemical function of simian virus 40 small t antigen, the inhibition of simian virus 40 large T antigen-mediated viral DNA replication in an in vitro replication system. Our results suggest that in this system, small t antigen prevents protein phosphatase 2A-mediated activation of large T antigen. PMID- 1310786 TI - Simian rotavirus SA11 strains. PMID- 1310785 TI - Use of suppressor analysis to identify DNA polymerase mutations in herpes simplex virus which affect deoxynucleoside triphosphate substrate specificity. AB - Herpes simplex virus DNA polymerase mutations which map in the N-terminal part of the protein and appear to alter deoxynucleoside triphosphate (dNTP) substrate specificity are described. These mutations suppress a drug hypersensitivity associated with the downstream mutation, Aphr10. We suggest that the mutant residues form part of the dNTP-binding site, a site previously thought to be confined to the C terminus. PMID- 1310787 TI - Fiber or no fiber in tube-fed patients. PMID- 1310788 TI - [Insufficient knowledge on the practical uses of high-fiber diet]. PMID- 1310789 TI - Neuropeptide Y receptor in bovine hippocampus is a Y2 receptor. AB - [125I]NPY bound to a single class of saturable binding sites on bovine hippocampus membranes with a KD of 0.1 mM and Bmax of 165 fmol/mg of protein. The rank order of potency of NPY fragments and other structurally related peptides to inhibit [125I]NPY binding was: PYY greater than or equal to NPY much greater than BPP greater than or equal to APP and NPY greater than NPY-(13-36) greater than NPY-(18-36) greater than or equal to NPY-(20-36) much greater than NPY-(26-36) greater than NPY-(free acid). The identity of the NPY binding site was investigated by affinity labeling. Gel electrophoresis followed by autoradiography revealed a band with a mol mass of 50 kDa. Unlabeled NPY or PYY, but not BPP, HPP and APP, inhibited labeling of [125I]NPY to the 50 kDa protein band. Moreover, labeling was inhibited by NPY greater than NPY-(18-36) greater than or equal to NPY-(13-36) greater than or equal to NPY-(20-36) greater than NPY-(26-36) greater than NPY-(free acid). The binding of [125I]NPY and the intensity of the cross-linked band were reduced in parallel by increasing concentrations of unlabeled NPY (IC50 = 0.7 nM and 0.6 mM, respectively). These studies demonstrate that bovine hippocampal membranes contain a 50 kDa [125I]NPY binding site that has the ligand specificity characteristic of the Y2 receptor subtype. PMID- 1310790 TI - The metabolic effects of oxytocin are mediated by a uterine type of receptor and are inhibited by oxytocin antagonist and by arginine vasopressin in the dog. AB - Infusion of oxytocin (OT) into normal dogs, in doses which produced plasma levels of OT in the physiological range, has been shown to increase plasma levels of glucose, insulin and glucagon and increase rates of glucose production and uptake. This study sought to determine whether there was a correlation between these metabolic effects and the oxytocic potency of four less potent oxytocic analogues when infused into normal dogs. The rank order of oxytocic potency of all 4 correlated well with the rise in plasma glucose levels, and in 3 of the 4 with the rise in plasma insulin levels. An antagonist of the oxytocic effect of OT suppressed the usual OT-induced rise in plasma glucose, insulin and glucagon as well as the increased glucose production and uptake. Arginine vasopressin (AVP) infusion, which by itself did not produce any metabolic effects, blocked completely the effects of OT infusion to raise plasma glucose and insulin levels and increase glucose production and uptake. The data suggest that the metabolic effects of OT in the dog are mediated by OT receptors that are similar to those producing the oxytocic effects. Whether the inhibition by AVP of the metabolic and hormonal effects of OT occurs at the receptor or post receptor level or via other mechanisms remains to be determined. PMID- 1310791 TI - Isolation and analysis of IS6120, a new insertion sequence from Mycobacterium smegmatis. AB - Insertion sequence IS6120 from Mycobacterium smegmatis was identified by its ability to transpose into different sites in the lambda repressor gene, cl857, carried on an Escherichia coli/mycobacteria shuttle plasmid. IS6120 is a novel 1.5 kb insertion sequence, which has 24-bp imperfect terminal inverted repeats and generates 9-bp duplications of the target DNA following insertion. IS6120 is present in at least three copies in M. smegmatis but was not found in other species, including Mycobacterium tuberculosis. Nucleotide sequence analysis revealed that IS6120 contains two open reading frames, one of which encodes a putative transposase with similarities to those found in IS256 from Staphylococcus aureus, IST2 from Thiobacillus ferrooxidans, and ISRm3 from Rhizobium meliloti. The fact that IS6120 does not recognize a consensus target sequence for insertion and has no homologous sequences in the other strains studied makes IS6120 useful for transposon mutagenesis in mycobacteria. PMID- 1310792 TI - Iron regulates growth of Trichomonas vaginalis and the expression of immunogenic trichomonad proteins. AB - Iron is an essential nutrient for Trichomonas vaginalis and is acquired via highly specific receptor-mediated mechanisms from the host. Responses of T. vaginalis to conditions of iron limitation or iron excess were analysed in order to determine whether iron levels in the growth medium regulate certain properties of the parasite. When compared with organisms grown in excess iron, iron limitation resulted in greater than or equal to 80% lower rates of protein synthesis and greater than or equal to 3-fold decreases in cell densities. These parasites also exhibited generation times of approximately 10 hours, 2.5-fold longer than organisms grown in the usual complex medium. Iron-restricted growth also resulted in increased binding of lactoferrin by trichomonads, which paralleled elevated expression of the lactoferrin-binding receptor protein having a relative molecular mass of 136,000 daltons (136 kDa). A Mr 126 kDa protein was concomitantly repressed in low-iron-grown parasites. The greater amounts of lactoferrin bound by iron-depleted T. vaginalis organisms corresponded with both the expression of additional receptors onto trichomonal surfaces and increased affinity of the receptor for the lactoferrin molecule. Finally, immunoblot analysis of parasites grown under high- and low-iron conditions using sera from patients with trichomoniasis further revealed the synthesis by T. vaginalis of at least 19 iron-regulated immunogens, and patients' sera also detected the lactoferrin receptor. These data not only show the overall importance of iron to the biology of this protozoan, but illustrate the in vivo iron modulation of gene expression of the biofunctional lactoferrin receptor and other immunogens. PMID- 1310793 TI - Glucose repression in the yeast Saccharomyces cerevisiae. AB - Understanding the mechanism of glucose repression in yeast has proved to be a difficult and challenging problem. A multitude of genes in different pathways are repressed by glucose at the level of transcription. The SUC2 gene, which encodes invertase, is an excellent reporter gene for glucose repression, since its expression is controlled exclusively by this pathway. Genetic analysis has identified numerous regulatory mutations which can either prevent derepression of SUC2 or render its expression insensitive to glucose repression. These mutations allow us to sketch the outlines of a pathway for general glucose repression, which has several key elements: hexokinase PII, encoded by HXK2, which seems to play a role in the sensing of glucose levels; the protein kinase encoded by SNF1, whose activity is required for derepression of many glucose-repressible genes; and the MIG1 repressor protein, which binds to the upstream regions of SUC2 and other glucose-repressible genes. Repression by MIG1 requires the activity of the CYC8 and TUP1 proteins. Glucose repression of other sets of genes seems to be controlled by the general glucose repression pathway acting in concert with other mechanisms. In the cases of the GAL genes and possibly CYC1, regulation is mediated by a cascade in which the general pathway represses expression of a positive transcriptional activator. PMID- 1310794 TI - Escherichia coli DNA helicases: mechanisms of DNA unwinding. AB - DNA helicases are ubiquitous enzymes that catalyse the unwinding of duplex DNA during replication, recombination and repair. These enzymes have been studied extensively; however, the specific details of how any helicase unwinds duplex DNA are unknown. Although it is clear that not all helicases unwind duplex DNA in an identical way, many helicases possess similar properties, which are thus likely to be of general importance to their mechanism of action. For example, since helicases appear generally to be oligomeric enzymes, the hypothesis is presented in this review that the functionally active forms of DNA helicases are oligomeric. The oligomeric nature of helicases provides them with multiple DNA binding sites, allowing the transient formation of ternary structures, such that at an unwinding fork, the helicase can bind either single-stranded and duplex DNA simultaneously or two strands of single-stranded DNA. Modulation of the relative affinities of these binding sites for single-stranded versus duplex DNA through ATP binding and hydrolysis would then provide the basis for a cycling mechanism for processive unwinding of DNA by helicases. The properties of the Escherichia coli DNA helicases are reviewed and possible mechanisms by which helicases might unwind duplex DNA are discussed in view of their oligomeric structures, with emphasis on the E. coli Rep, RecBCD and phage T7 gene 4 helicases. PMID- 1310795 TI - Hereditary tumours of childhood. Messages for cancer in general. PMID- 1310796 TI - Use of a specimen-evaluation device for the diagnosis of impalpable breast lesions detected by mammography. AB - OBJECTIVE: To describe a method for accurate excision and exact histopathological diagnosis of impalpable breast lesions, considered suspicious of carcinoma, and detected on mammographic examination alone. SETTING, PATIENTS AND INTERVENTIONS: Eight-five patients referred with a suspicious but impalpable mammographic lesion underwent preoperative radiological localisation followed by surgical excision biopsy. Specimen radiology with a radiolucent acrylic compression-grid specimen evaluation device confirmed that the lesion had been excised. By use of the grid coordinates, exact histopathological examination of the radiological area of suspicion was carried out to provide a definitive pathological diagnosis. RESULTS: Twenty-eight patients (33%) were found to have invasive carcinoma or extensive intraduct breast carcinoma requiring further surgical and adjuvant management. Nineteen of these patients (68%) had no axillary node metastases. CONCLUSION: The use of an acrylic compression-grid specimen-evaluation device in the diagnosis of suspicious mammographic breast lesions facilitates confirmation of excision by specimen radiology, and expedites accurate histological examination of suspicious radiological lesions. PMID- 1310797 TI - Effects of okadaic acid, a protein phosphatase inhibitor, on glucocorticoid receptor-mediated enhancement. AB - The effects of okadaic acid (OA), a protein phosphatase inhibitor, on transcriptional enhancement activity of rat glucocorticoid receptor (GR) were examined in transiently transfected cells. In the absence of hormone, GRs expressed in CV-1 and COS-1 fibroblasts were capable of enhancing transcription from cotransfected chloramphenicol acetyltransferase reporter plasmids in response to OA treatment. Synergistic enhancement resulted from combined hormone and OA treatment. The effects of OA on GR-mediated enhancement required the presence of linked glucocorticoid response elements and were observed with reporter plasmids that contained different promoters and glucocorticoid response elements. Since OA did not affect nuclear translocation of the receptor, enhancement mediated by unliganded GR was most likely accounted for by the accumulation of some unliganded GRs within nuclei of transfected CV-1 and COS-1 cells. Deletion of individual GR transactivation domains and point mutations within DNA- and hormone-binding domains severely reduced the response of receptors to OA, although some mutant receptors retained the capacity to elicit a synergistic response when exposed to OA and hormone. The effects of OA on transcriptional enhancement did not appear to correlate with major changes in GR phosphorylation, as visualized by two-dimensional tryptic mapping of in vivo 32P labeled GRs. Thus, phosphorylation of various components of the GR signal transduction pathway, and not necessarily the receptor itself, may influence its transcriptional enhancement activity. PMID- 1310798 TI - Insulin-like growth factor-II overexpression in MCF-7 cells induces phenotypic changes associated with malignant progression. AB - It has been proposed that the insulin-like growth factors (IGFs) can act as autocrine and/or paracrine growth promoters in breast cancer. To investigate this hypothesis, we infected early passage MCF-7 cells with a retroviral vector containing the coding sequence for the IGF-II preprohormone along with a constitutive cytomegalovirus promoter sequence. These cells do not normally express IGF-I or IGF-II. After infection with the retroviral vector, several single cell clones were analyzed. Seven of nine isolated clones expressed very high levels of IGF-II mRNA. Biologically active IGF-II protein was easily detectable in the medium conditioned by the IGF-II-expressing clones, and IGF receptors were down-regulated in these. All IGF-II-expressing clones showed marked morphological changes in anchorage-dependent culture, growing in large clumps and as free-floating colonies. The cells also cloned in soft agar in the absence of estrogen, while the wild-type MCF-7 cells and control cells infected with an irrelevant DNA sequence showed none of these properties. alpha IR-3, an antibody that blocks the type I IGF receptor, inhibited the growth of IGF-II expressing clones in serum-free medium. This model demonstrates that IGF-II can serve as an autocrine growth stimulant in breast cancer epithelial cells and that IGF-II overexpression may be capable of mediating malignant progression in human breast cancer. PMID- 1310799 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 11-1992. Increasing dyspnea and cough in a 77-year-old man with interstitial lung disease. PMID- 1310800 TI - High incidence of hepatitis C virus antibodies in hemodialysis patients. PMID- 1310801 TI - Early and rapid diagnosis of CMV infection by nonradioactive in situ hybridization in pediatric kidney transplant recipients. AB - A nonradioactive in situ hybridization technique was utilized for the rapid and early diagnosis of cytomegalovirus (CMV) infection in children undergoing kidney transplantation. The cellular samples were obtained directly from the organs thought to be affected on the basis of clinical findings: bronchoalveolar lavage during interstitial pneumonia (7 samples from 6 cases); fine-needle aspiration biopsy (FNAB) of the liver during acute hepatitis (1 case); kidney FNAB and peripheral blood where there was a greater than or equal to 25% creatinine rise with or without fever (26 episodes). Standard virus isolation procedures and an immunofluorescent technique on short-term cultures of human fibroblast cells were performed as a control. 6/23 children followed had a symptomatic CMV infection (4 had interstitial pneumonia; 1 had acute hepatitis, and there was 1 case of creatinine rise with fever). In all cases, the diagnosis was provided by in situ hybridization in less than 24 h. These results were confirmed 48 h later by immunofluorescence and after 5-25 days by standard viral cultures. In situ hybridization with a biotinylated probe proved to be a rapid and sensitive method for diagnosis of CMV disease, when performed on specimens obtained from the involved organs at an early stage of the infection. This diagnostic approach allowed a specific antiviral therapy to be undertaken promptly. PMID- 1310802 TI - [Malignant transformation of benign mixed tumor of lacrimal gland to squamous cell carcinoma 19 years after initial surgery: report of a case]. AB - A case of malignant transformation of benign mixed tumor (pleomorphic adenoma) arising from the right lacrimal gland is reported. A 63-year-old man was referred to our clinic because of visual disturbance and protrusion of the right eye in January, 1989. His past history revealed that he had had a benign mixed tumor of the right lacrimal gland resected 19 years ago. On CT scan, an iso-density lesion homogeneously enhanced with contrast medium was found in the right orbit. This tumor was partially cystic and invaded the cranial cavity. On T1 and T2 weighted MRI, the tumor appeared as an iso-intensity area. At surgery, the tumor was subtotally resected via the combined fronto-orbital approach on February 3, 1990. Histological diagnosis of the tumor was squamous cell carcinoma, and it was construed to be a malignant transformation of mixed tumor of the lacrimal gland. Postoperatively he was placed on a course of external radiation therapy (63 Gy in total) in combination with intra-carotid Cisplatin injection therapy. The first sign of the recurrence was seen as multiple metastatic lesions in both lungs about 4 months after the surgery. In December, 1990, protrusion of the left eye and disturbance of ocular movement became progressively worse. On CT scan, recurrent metastatic tumor was seen in the left orbit and paranasal sinuses. Although additional chemotherapy and irradiation brought about a short period of symptomatic relief he succumbed to pneumonia in April 18, 1990. Metastatic squamous cell carcinoma was confirmed in the lung at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310803 TI - [A case of spinal cord glioblastoma multiforme]. AB - A 35-year-old woman was admitted to our hospital with a 3 month history of progressive paraparesis and impairment of bowel and bladder function. MRI suggested a malignant glioma at the level of T9 to L1. Laminectomy and subtotal removal of the tumor was performed. The surgical specimen was a glioblastoma multiforme. An aggressive adjuvant therapy was scheduled to prevent rapid local regrowth and leptomeningeal dissemination. Radiotherapy with a total dose of 65Gy was delivered with chemotherapy including ACNU (2mg/kg) and vincristine (0.2mg/kg). Lymphokine-activated killer (LAK) cells were given intrathecally with a total dose of 1.6 x 10(9) LAK cells with 3 x 10(4) units of IL-2. MRI taken 6 months after surgery revealed no residual tumor, and no malignant cell was detected in the patient's CSF. After physiotherapy, she became able to walk with a stick and was discharged. Chemotherapy (ACNU 2mg/kg/8 weeks) had been further continued for 2 years. She did well until 14 months after surgery, when paraparesis recurred and rapidly progressed to completism. MRI revealed a spinal cord swelling with marked edema, suggesting delayed radiation necrosis. Two years after surgery, MRI showed a marked atrophy of the spinal cord, and no residual tumor. But 3 years after surgery, a round tumor at the level of T11 and T12 was revealed on MRI, and she was admitted to our hospital again. A spinal cord amputation was performed, and the tumor was totally removed without worsening her neurological symptoms. Surgical specimen of the tumor was glioblastoma multiforme again.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310804 TI - High frequency of latent and clinical human papillomavirus cervical infections in immunocompromised human immunodeficiency virus-infected women. AB - In 32 human immunodeficiency virus (HIV)-infected women, routine gynecologic examination was performed with colposcopy and Papanicolaou smear; cervical swabs were collected for human papillomavirus (HPV) DNA screening and typing; and immune status was assessed by CD4 T-cell count. Dot blot analysis was specifically chosen for HPV DNA screening to detect only relatively substantial HPV DNA infections. Polymerase chain reaction analysis was used for precise DNA typing of dot blot-positive samples. The HPV data were assessed for immune status; a subject with a CD4 T-cell count below 200/microL was considered functionally immunosuppressed. The frequency of dot blot positivity was fivefold higher among immunocompromised (nine of ten) than relatively immunocompetent (four of 22) HIV-infected women. Moreover, four immunosuppressed women, compared with no immunocompetent subjects, had evidence of HPV DNA without signs of HPV associated lesions by cytology or histology (ie, latent HPV infection). Furthermore, four of nine of the immunocompromised, compared with four of 21 immunocompetent, subjects had cervical intraepithelial neoplasia. These frequencies are high compared with those reported in the general population. Finally, HPV 18 was detected in five of the ten women with CD4 T-cell counts below 200/microL and in only one of the 22 with CD4 T-cell counts above that level. These results suggest that the normal immune system suppresses latent and clinical HPV cervical infections and that the efficiency of suppression may be HPV type-specific. Furthermore, impaired immune status, as reflected by CD4 T cell count, is an important factor increasing the severity of HPV-induced cervical infections in this population. PMID- 1310806 TI - Carcinoma of the vulva: epidemiology and pathogenesis. AB - Vulvar squamous carcinoma is an uncommon neoplasm that afflicts a spectrum of women and has been associated with granulomatous vulvar diseases, human papillomaviruses (HPVs), and chronic inflammatory disorders of the vulva. This review summarizes the epidemiologic, histopathologic, and viral data supporting the division of invasive vulvar carcinomas into distinct subsets. Although HPVs have received attention as etiologic agents, histopathologic and viral data indicate that a substantial proportion of vulvar carcinomas in this country may not be related to a veneareally transmitted agent. One of the principal challenges is to produce studies integrating the various disciplines in order to place HPV in proper perspective and develop strategies to identify women at risk for vulvar carcinomas that are not associated with this virus. PMID- 1310805 TI - Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. AB - During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer. PMID- 1310807 TI - Polymerase chain reaction amplification of herpes simplex virus DNA from clinical samples. AB - The polymerase chain reaction was used to amplify herpes simplex virus (HSV) DNA from 79 clinical specimens from the female genital tract, and the results were compared with cell culture. Combining the polymerase chain reaction with visualization of amplified products using a direct gel analysis, HSV DNA was detected in 38 specimens, six of which were negative for virus by cell culture. Hybridization of the amplified products detected HSV in three other specimens. One specimen was positive for HSV by cell culture but negative for viral DNA by polymerase chain reaction. Specimen purification before the polymerase chain reaction improved the detection of viral DNA. Restriction endonuclease cleavage of amplified DNA seen by direct gel analysis, used to differentiate HSV-1 from HSV-2, was correct in each case. The analysis time using the polymerase chain reaction was 8-10 hours, making this technique potentially valuable in the clinical setting of parturition. PMID- 1310808 TI - Adenoid cystic carcinoma of the external auditory canal. PMID- 1310809 TI - Sequence analysis of the BZLF 1 gene of Epstein-Barr virus derived from a new variant isolated in Taiwan. PMID- 1310810 TI - Pyridoxol L,2-pyrrolidon-5 carboxylate prevents active fibroplasia in CCl4 treated rats. AB - In the present study we evaluated the protective activity of pyridoxol L,2 pyrrolidon-5 carboxylate (metadoxine) against CCl4 intoxication in rats, especially in relation to liver fibrosis. After 6 consecutive weeks of CCl4 treatment, the animals developed liver fibrosis and inflammation as revealed by histological analysis which also included semiquantitative scoring of these features. In addition the serum levels of the immunoreactive prolyl hydroxylase (SIRPH), an enzyme involved in the hydroxylation of the procollagen molecule, were significantly higher (44.2 +/- 16.3 micrograms/ml; P less than 0.005) in this group of animals than in controls (26.1 +/- 8.06). On the contrary, animals treated with CCl4 + metadoxine (200 mg/kg i.p.) had less severe liver fibrosis and normal SIRPH levels (21.5 +/- 14.6). These data suggest that metadoxine may be an effective pharmacological tool for preventing the progression of liver disease in rats exposed to CCl4 to cirrhosis. PMID- 1310811 TI - Lithium treatment regimens induce different changes in [3H]paroxetine binding protein and other rat brain proteins. AB - Rats were treated with lithium administered either via the food or by intraperitoneal injection. Lithium administration via the food results in a rather stable serum lithium concentration, whereas lithium injection results in a varying serum lithium concentration whereby a sharp increase shortly after the injection is followed by an exponential decline until the next injection (Plenge et al. 1981). After 5 months of lithium treatment the 5HT transport protein, the beta-adrenergic receptor and several other brain proteins were determined. The 5HT transport protein, labelled with [3H]paroxetine, was found to be decreased in the lithium-injected rats (Bmax = 347 fmol/mg protein) but was unchanged in the lithium-fed rats (Bmax = 389 fmol/mg protein), as compared with control rats (Bmax = 396 fmol/mg protein), and therefore probably is a specific effect only seen with varying lithium concentration. In contrast, the neuronal membrane marker protein D3 was decreased in the lithium-fed rats (88% of the control value), and showed a trend towards decrease in the lithium-injected rats. The decrease in D3 in the lithium-fed rats may indicate some neuronal damage due to the continuous presence of lithium. This damage may be more pronounced than in rats, where periods of low lithium concentration enable repair to take place. The beta-adrenergic receptor and the neural cell adhesion molecule NCAM were unaffected by the different lithium treatment regimens. Lithium has been reported to inhibit the 5HT1B receptor (the serotonin autoreceptor).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310812 TI - Analysis of monoclonal rheumatoid factors obtained from the B-cell repertoire in rheumatoid arthritis. AB - We have sought to determine whether rheumatoid factors (RF) produced in rheumatoid arthritis (RA) were different from physiological RF produced in normal, healthy adults. RF-secreting clones were established following Epstein Barr virus (EBV) stimulation of peripheral blood lymphocytes. Ten RF-secreting clones were established from seven RA patients and 16 from six healthy controls. All monoclonal RF (MRF), except two in each group, were monoreactive and ten of these were shown to have low to medium affinity for IgG,Fc, irrespective of their origin. A majority (74%) of the MRF bound to protein A, indicating that genes of the VHIII family were preferentially used for synthesizing these autoantibodies. The expression of cross-reactive idiotypes (CRI) by the MRF did not allow distinction between those derived from RA patients and controls. The VHI associated CRI G8 and VHIII-associated CRID12 were expressed at low frequency in both panels of RF. These CRI have been shown to be expressed at high frequency in RF paraproteins. However, the idRQ idiotype was expressed within both panels of RF. A possible distinction between polyreactive and monoreactive MRF appeared to be light chain usage since all (four) polyreactive RF used lambda chains while the normal kappa/lambda ratio was observed for monoreactive RF. The frequency of EBV-activated cells secreting IgM bearing CRI or secreting RF was determined and showed that CRI expression occurred with a higher frequency than did RF, suggesting a dissociation between CRI expression and RF activity. PMID- 1310813 TI - Interleukin-4 down-regulates Sendai virus-induced production of interferon-alpha and -beta in human peripheral blood monocytes in vitro. AB - Recombinant interleukin-4 (rIL-4) caused a 65-70% reduction of the interferon alpha (IFN-alpha) and -beta production induced by Sendai virus (SV) in human peripheral blood monocytes in vitro. Significant inhibition was seen at concentrations as low as 0.1 ng/ml. The rIL-4 also reduced levels of IFN-alpha and -beta mRNA by 60% and 67%, respectively, as well as the frequency of IFN alpha and -beta mRNA-containing cells by 65% and 54%, respectively. The frequency of IFN-alpha/beta mRNA-containing cells was inhibited by rIL-4 throughout the whole course of induction by SV. IL-4 caused a shift of the grain count distribution towards less heavily labelled cells, suggesting an inhibitory effect of rIL-4 on most IFN-alpha/beta mRNA-containing cells. Antibodies to rIL-4 did not influence the normal IFN-alpha/beta response induced by SV, but abolished the inhibitory effect of the rIL-4. When rIL-4 was added to cells 4 h after start of stimulation by SV, at which time much mRNA has accumulated but little IFN alpha/beta has been secreted, no inhibition of the IFN-alpha/beta production by rIL-4 was seen. IFN-gamma had only a minor reversing effect on the rIL-4 inhibition, but if cells were precultivated in medium with or without IFN-gamma for 6 h before SV induction, rIL-4 paradoxically enhanced the IFN-alpha/beta response. Our results suggest that rIL-4 inhibits an early step of IFN-alpha/beta induction in monocytes, at the level either of transcription of IFN-alpha/beta genes or of the processing or stability of mRNA. The IL-4 effects may however depend on the state of activation of the monocytes. PMID- 1310814 TI - Interferon-alpha but not -beta genes require de novo protein synthesis for efficient expression in human monocytes. AB - Monocytes produce interferon-alpha (IFN)-alpha) and -beta when human peripheral blood mononuclear cells (PBMCs) are stimulated in vitro by Sendai virus (SV). We found that about 70% of the IFN-producing cells (IPCs) expressed both IFN-alpha and -beta mRNA; the rest expressed only IFN-beta mRNA. In the presence of the protein synthesis inhibitor cycloheximide (CHX), the frequency of IFN-alpha mRNA containing cells, measured after 6h, was decreased by 85-90%. Results of nuclear run-on transcription assays showed that CHX inhibited IFN-alpha gene expression. The frequency of IFN-beta mRNA-containing cells was not reduced by CHX. Actually, a threefold increase was observed at the lower CHX concentrations. Studies on the kinetics of IFN-alpha/beta mRNA induction showed that CHX accelerated the appearance of IFN-beta mRNA-containing cells, increased IFN-beta mRNA levels, and delayed the normally occurring post-inductional decrease of IFN-beta mRNA. Unexpectedly, an initially normal or even accelerated IFN-alpha mRNA response was seen in the presence of CHX during the first 3-4 h after SV stimulation. This occurred in a small proportion of the potential IPCs. However, CHX prevented the subsequent marked increase of IFN-alpha mRNA levels. Preincubation of PBMCs for 6 h in conditioned medium (CM) containing IFN and other cytokines prevented the CHX mediated inhibition of IFN-alpha mRNA. Without preincubation this was not seen. The preincubation in CM caused an accelerated appearance of IFN-alpha mRNA, resembling that of IFN-beta mRNA. The results suggest that IFN-alpha and -beta genes are differentially regulated in the same monocytes, the former requiring de novo synthesis of intracellular protein(s) for efficient expression. PMID- 1310815 TI - T-cell receptor beta-chain gene rearrangements of T-cell populations expanded from multiple sites of synovial tissue obtained from a patient with rheumatoid arthritis. AB - In this study T-cell receptor (TcR) beta-chain gene rearrangements of T-cell lines prepared from multiple sites (n = 92) of synovial tissue derived from both knees of a patient with rheumatoid arthritis were analysed. In the majority of T cell lines, dominant TcR beta-chain gene rearrangements were detected, involving C beta 1 as well as C beta 2. The dominant rearrangement patterns of T-cell lines from different tissue fragments showed significant variability, but some of the DNA restriction fragments were shared by T-cell lines from multiple sites in both knees. The latter observation suggests that identical T-cell clones may be present at different sites in the synovial tissue and in different joints. However, since many T-cell lines yielded different rearrangement patterns, these data also indicate considerable heterogeneity of T cells in the joints. Apart from theoretical implications, this TcR heterogeneity of T cells within an individual patient also has practical consequences for studies on synovial T cells obtained by biopsy. PMID- 1310816 TI - Prolonged elevation of intracellular cyclic AMP activates interleukin-1 production in human peripheral blood monocytes. AB - The capability of elevated intracellular cyclic AMP concentration to activate IL 1 gene expression and protein production was examined in human peripheral blood monocytes. In accordance with previous studies it was observed that the transiently elevated cyclic AMP (induced either with prostaglandin E2 or with the direct adenylate cyclase activator, forskolin) was not a sufficient signal to activate IL-1 production. However, if the degradation of cyclic AMP was inhibited with isobutyl-methyl-xanthine (IBMX), IL-1 production was strongly activated. This prostaglandin E2 plus IBMX effect could also be mimicked with high concentrations of the cell permeant structural cyclic AMP analogue, dibutyryl cyclic AMP. The cyclic AMP-induced IL-1 production differed in some aspects from the bacterial lipopolysaccharide-induced IL-1 production: (1) the kinetics of both IL-1 gene expression and protein production was much slower; (2) the IL-1 beta gene expression was superinducible by inhibiting the protein synthesis with cycloheximide. Thus these data suggest that prolonged elevation of cyclic AMP is alone a sufficient signal to activate IL-1 production. PMID- 1310817 TI - Relationship between breast cancer and meningioma. AB - Several authors have suggested the existence of a relationship between breast cancer and meningioma occurring in the same patient. I describe four patients who had both of these neoplasms and present findings that dispute the implied relationship between the two. PMID- 1310818 TI - Undifferentiated small cell carcinoma of the urinary bladder. AB - We have reported a case of small cell carcinoma of the urinary bladder in a 65 year-old white man with a smoking history. He had radical cystectomy, but died 6 months after initial diagnosis. The patient terminally had liver metastasis, confirmed by fine needle aspiration and radiographic evidence of intra-abdominal and right adrenal gland metastasis. PMID- 1310819 TI - Primary squamous cell carcinoma of the breast. AB - We have described three patients with primary squamous cell carcinoma of the breast. All three have remained well after modified radical mastectomy. One patient received postoperative radiotherapy. Estrogen receptor status was determined by monoclonal antibody technology in two cases, and the results were negative. PMID- 1310820 TI - Malignant fibrous histiocytoma arising from the superficial femoral artery. AB - Primary sarcomatous arterial tumors are rare. We have reported a case of malignant fibrous histiocytoma in an elderly woman successfully treated by resection of the involved femoral vessel and reconstruction with a PTFE graft. The long-term result in this patient is presently uncertain. PMID- 1310821 TI - Nonspecificity of serological tests for cytomegalovirus. PMID- 1310823 TI - Liver transplantation for primary hepatic cancer. AB - Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this indication. Since the inception of the Boston Center for Liver Transplantation (BCLT) in 1983, 33 of 383 (8.6%) liver allograft recipients have undergone orthotopic transplantation as definitive treatment for otherwise unresectable cancer. Diagnoses included hepatocellular carcinoma (HCCA) in 24 patients (73%), and cholangiocarcinoma (CHCA) in 9 patients (27%). Actuarial survival rates for patients with hepatocellular carcinoma were 71%, 56%, and 42% at 1, 2, and 3 years, respectively. The actuarial survival rates for patients with cholangiocarcinoma were 89% at 6 months, and 56% at 1, 2, and 3 years. Of the nine patients with cholangiocarcinoma, 56% (5/9) developed recurrent disease. Although this recurrence rate is disheartening, because of the lack of other morbidity, long-term survival in these patients is comparable to patients with HCCA. In contrast, recurrent hepatocellular carcinoma developed in 25% of recipients (5/20) who survived longer than 3 months posttransplantation. Other causes of death in patients with hepatocellular carcinoma included perioperative complications, 16.6% (4/24); sepsis, 8.3% (2/24); coronary artery disease, 4.2% (1/24); and lymphoma, 4.2% (1/24). Favorable prognostic factors included: primary tumor less than 3 cm in size and absence of associated cirrhosis. These results emphasize that orthotopic liver transplantation can provide a long-term cure for approximately 50% of patients whose primary hepatic malignancy is unresectable by conventional procedures. PMID- 1310822 TI - Regulation of pulmonary resistance during cardiopulmonary preservation. AB - To characterize the neural and vasoactive mediators of pulmonary vasoconstriction and determine whether the beneficial effect of isoproterenol could be mimicked by other agents that increase cyclic adenosine monophosphate, heart and lung organ blocks were harvested from calves and studied in a normothermic autoperfusion circuit. In the experimental protocol, measurements were obtained (A) after sternotomy but before autoperfusion (in vivo); (B) during stimulation of in vivo control with tert-butyl hydroperoxide (t-BuOOH), a lipid peroxide; (C) after cannulation and institution of in situ autoperfusion (innervated preparation); (D) following denervation and explanation (ex vivo); (E) during stimulation of ex vivo preparation with t-BuOOH; and (F,G) after administration of isoproterenol, aminophylline and prostaglandin E1 to the ex vivo preparation with (time G) and without (time F) stimulation using t-BuOOH. Plots of transpulmonary pressure gradient versus cardiac output were generated for each animal, and an index of pulmonary vascular resistance was obtained from the slope of the linear relationship. Blood samples were collected for measurement of thromboxane-B2, 6 keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Pulmonary vasoconstriction occurred during in situ autoperfusion prior to denervation and increased further following denervation and ex vivo autoperfusion; vasoconstriction correlated with increased levels of circulating vasoactive mediators. The pulmonary vasoconstrictor response was greater in the denervated vascular bed compared with the innervated state. All agents reduced postexplant pulmonary vasoconstriction. We conclude that agents that increase cyclic AMP modulate the pulmonary vasoconstrictor response and thus may enhance lung preservation in the autoperfusion model as well as with other current preservation methods. PMID- 1310825 TI - The positive predictive value of mammography. PMID- 1310824 TI - Severe aseptic synovitis of the knee after biodegradable internal fixation. A case report. AB - Biodegradable rods made of polyglycolide (Dexon, Biofix) or lactide-glycolide copolymer (Vicryl) have been used for the past 5 years for internal fixation of a variety of fractures and osteotomies (Bostman et al. 1989, 1990b). Experience from using such rods for fixation of intraarticular osteochondral lesions seems to be less extensive. We report a case of severe synovial reaction to biodegradable rods used for fixation of osteochondritis dissecans of the knee and discuss possible reasons for the increased risk of foreign-body reactions when these rods are used intraarticularly. PMID- 1310826 TI - Color Doppler sonography of hepatocellular carcinoma before and after treatment by transcatheter arterial embolization. AB - Color Doppler sonographic findings on 38 lesions in 31 patients who had primary hepatocellular carcinoma were evaluated before and after transcatheter arterial embolization and compared with dynamic CT and hepatic arteriographic findings. All lesions that were observed with dynamic CT or arteriography were correctly identified on color Doppler sonography. Peritumoral pulsatile flow was the predominant color Doppler flow seen in all lesions. Mixed pulsatile and continuous flow were noted in larger tumors and in tumors with a higher degree of vascularity, as determined by arteriography. Two weeks after treatment, color Doppler flow was still identified in 18 lesions (47%), corresponding to dynamic CT or arteriographic findings documenting residual tumor. Histopathologic examination, performed in 10 other lesions, showed that the tumor was completely necrotic in five. These five necrotic tumors were not visible on color Doppler flow images after treatment. Viable tumor was observed in the five remaining lesions, all of which were shown on color Doppler flow images after treatment. During the 6- to 16-month follow-up period, color Doppler flow images showed recurrence of 13 (50%) of 26 lesions, corresponding to tumor recurrence as shown by CT and arteriography. We conclude that color Doppler sonography is useful for imaging hepatocellular carcinoma, for evaluating residual tumor after treatment, and for imaging tumor recurrence during follow-up. PMID- 1310827 TI - Renal handling of enalaprilat. AB - Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion. PMID- 1310828 TI - CDC surrenders to health groups on AIDS strategy. PMID- 1310829 TI - Correlation of the expression of Epstein-Barr virus latent membrane protein and in situ hybridization with biotinylated BamHI-W probes in Hodgkin's disease. AB - The detection of Epstein-Barr virus (EBV) nucleic acids by in situ hybridization (ISH) with biotinylated BamHI-W probes was correlated with the expressions of EBV latent membrane protein (LMP) and EB nuclear antigen 2 (EBNA2), in 107 cases of Hodgkin's disease (HD) of different immunomorphologic subtypes. Epstein-Barr virus nucleic acids were present and restricted to the pathogenic cells in 4 of 40 (10%) cases of nodular sclerosis (NS) and 33 of 55 (60%) cases of mixed cellularity (MC), but were undetectable in other subtypes. Of the 37 cases positive for EBV nucleic acids, 35 (95%) showed the expression of LMP. Epstein Barr virus nucleic acids and LMP were restricted to Reed-Sternberg cells and variants. Only 1 case (MC) showed LMP expression in the absence of EBV detection. The correlation was strengthened by the finding of LMP expression at first diagnosis in 6/7 EBV positive cases at relapse (14-126 months) (5/5 EBV negative cases at relapse were LMP negative at first diagnosis). EBNA2 was absent in all 13 (NS, 2; MC, 11) EBV+ and LMP+ cases tested. Both LMP and EBNA2 were expressed in control EBV-positive tissues and cell lines. EBV serology in MC HD was indicative of latent EBV infection, but neither serology nor clinical parameters correlated with the presence or the absence of EBV, over a short-term follow-up (median, 20 months). The findings, although not proving EBV as the etiologic agent of HD, suggest that: 1) LMP expression alone may be adequate for identifying EBV-associated HD, 2) the MC subtype has a stronger relation with EBV presence, and 3) the regulation of EBV genes in HD is different from other EBV associated disorders. The clinical implications still remain to be discovered. PMID- 1310830 TI - Human papillomavirus 16 DNA immortalizes two types of normal human epithelial cells of the uterine cervix. AB - Premalignant cervical lesions occur at the squamo-columnar junction and in endocervical epithelium and squamous ectocervical epithelium, in descending order of frequency. However, previously only ectocervical cells have been clearly shown to be immortalized in vitro by the oncogenic human papillomaviruses (HPVs). This report describes the immortalization of normal human ecto- and endocervical epithelial cells by the intact HPV 16 genome. Ectocervical epithelial cells (HEC) became immortalized (HEC-16) without crisis while endocervical cells (HEN) were immortalized (HEN-16) after undergoing crisis. HEN-16 and HEC-16 contained integrated HPV 16 DNA, expressed E6 and E7 mRNA, and were aneuploid and nontumorigenic. They also expressed cytokeratins in a pattern similar to their distinct normal parental cells. These results suggest that both squamous and simple epithelial cells of uterine cervix are targets for immortalization by HPV 16. PMID- 1310831 TI - Lack of ubiquitin immunoreactivities at both ends of neuropil threads. Possible bidirectional growth of neuropil threads. AB - Immunocytochemically, neuropil threads (curly fibers) were investigated in the Alzheimer's disease brain using a confocal laser scanning fluorescence microscope by double labeling with tau/ubiquitin antibodies. Ubiquitin immunoreactivities were found to be lacking at one or both ends in more than 40% of tau-positive threads. Immunoelectron microscopy showed that bundles of paired helical filaments, which constitute neuropil threads, were positive for ubiquitin around their midportions, but often negative at their ends. Since it is reasonable to postulate that tau deposition as paired helical filaments precedes ubiquitination, the aforementioned observation suggests that the ends of the threads are newly formed portions, and thus the threads are often growing bidirectionally in small neuronal processes. PMID- 1310832 TI - Cellular localizations and processing of the two molecular forms of the Hodgkin associated Ki-1 (CD30) antigen. The protein kinase Ki-1/57 occurs in the nucleus. AB - The Ki-1 antibody not only detects a Hodgkin-associated membrane molecule of 120 kd (Ki-1/120 = CD30), but also reacts with an independently synthesized molecule of 57 kd (Ki-1/57) that only occurs intracellularly. Hodgkin's disease-derived cell lines L428 and L540 contain both Ki-1-reactive antigens, whereas others, e.g., U266/Bl myeloma cells, only express the intracellular Ki-1/57. The present immunoelectronmicroscopic analysis detected the Ki-1/57 antigen of U266/Bl cells not only in the cytoplasm, but also in association with the nuclear envelope, chromatin structures, and nucleoli. This Ki-1/57-specific type of labeling also was observed in L428 and L540 cells that, in contrast to U266/Bl cells, showed an additional staining of cell membranes and cytoplasmic vesicles. These results were confirmed by two independent methods: 1) cytocentrifuge preparations of isolated nuclei of L540 cells showed a spotted Ki-1-specific labeling, 2) immunoprecipitations demonstrated that the Ki-1/57, but not the Ki-1/120 antigen, was transferred into the nuclei of L540 and U266/Bl cells, whereas the Ki-1/120 antigen with its 90-kd precursor remained in the non-nuclei fraction of L540 cells. PMID- 1310833 TI - Human papillomavirus and the three group metaphase figure as markers of an increased risk for the development of cervical carcinoma. AB - In this study, the presence of atypical mitotic figures and human papilloma virus (HPV) genomes was related to the degree of cervical intraepithelial neoplasia (CIN) or microinvasive carcinoma (MIC) as found in 94 paraffin-embedded biopsies from cervical lesions. The results showed that the frequency of three group metaphase (TGM) figures, a special kind of atypical mitotic figure, as well as the presence of HPV 16 and 18 genomes increased with the degree of cervical intraepithelial neoplasia. TGM figures were observed in 24% of CIN2, up to 61% in CIN3 lesions, and in 83% of the microinvasive cervical carcinomas. HPV genomes were detected in 15% of CIN1, up to 75% in CIN3 lesions, and in 92% of the invasive carcinomas of the cervix. The combination of these two markers showed even a better association with a higher degree of cervical intraepithelial neoplasia. The results of these studies suggest that detection of particular HPV types, mainly HPV 16 and 18, and the presence of TGM figures can be considered as markers that indicate an increased risk for progression of cervical intraepithelial neoplasia to invasive carcinoma. PMID- 1310835 TI - Wheat-dependent exercise-induced anaphylaxis: inhibition by sodium bicarbonate. AB - We present a case of wheat-dependent exercise-induced anaphylaxis, in which pretreatment with sodium bicarbonate inhibited reappearance of anaphylactic symptoms following wheat and exercise provocation. Decrease in blood pH relative to elevation in plasma histamine levels was also inhibited. These results suggest possible efficacy of pretreatment with sodium bicarbonate as a preventive measure in patients with exercise-induced anaphylaxis. PMID- 1310834 TI - Effects of nedocromil sodium, cromolyn sodium, and a placebo in exercise-induced asthma. AB - The incidence and severity of exercise-induced asthma were determined in nineteen asthmatic patients who performed eight minutes of exercise following four treatments administered in a random order. The treatments were nedocromil sodium, cromolyn sodium, placebo, and no treatment. It was concluded that nedocromil sodium (8 mg) and cromolyn sodium (4 mg) provide equal protection against exercise-induced asthma. PMID- 1310836 TI - Underutilization of Rh prophylaxis in the emergency department: a retrospective survey. AB - STUDY OBJECTIVE: To determine the practice of emergency physicians with regard to the issue of Rh isoimmunization. DESIGN: A retrospective chart review. SETTING: A university-affiliated tertiary care hospital emergency department. TYPE OF PARTICIPANTS: Pregnant women presenting with a risk factor for Rh sensitization. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-eight patient encounters were analyzed descriptively as to whether they were candidates for Rh immune prophylaxis, and if so, whether it was given. Most (68%) were hospitalized. Of those, all were Rh typed, but two patients were not given Rh immune globulin (RhIG) when indicated. Of those discharged from the ED, most (86%) were not Rh typed, and none was administered RhIG. CONCLUSION: This study demonstrates a need for increased attention to the potential for Rh isoimmunization in patients presenting to the ED. PMID- 1310837 TI - Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes. AB - OBJECTIVE: To determine frequency, anatomic site, and host factors associated with asymptomatic shedding of herpes simplex virus after initial episodes of genital herpes. DESIGN: Cohort study with follow-up for a median of 63 weeks. SETTING: Referral clinic. PATIENTS: Women (306) with first episode of herpes; 43 had primary herpes simplex virus type 1, and 227 and 36 had primary and nonprimary herpes simplex virus type 2, respectively. MEASUREMENTS: Cultures were obtained for herpes simplex virus every 4 to 6 weeks at times in which genital lesions and symptoms were not present. MAIN RESULTS: Asymptomatic shedding was detected among 11.9%, 18.3%, and 22.9% of women with primary herpes simplex virus type 1, primary HSV type 2, and nonprimary HSV type 2, respectively. Among patients with type 2 infection, previous type 1 antibody was associated with a lower rate of asymptomatic vulvar shedding. Asymptomatic cervical shedding was 3 times more frequent during the first three months after resolution of primary type 2 disease than during later time periods. In contrast, the rate of symptomatic recurrent herpes did not change over time. CONCLUSIONS: Asymptomatic genital herpes simplex type 2 is more common than type 1. Asymptomatic genital shedding occurs more often during the first 3 months after acquisition of primary type 2 disease than during later periods. Patients with HSV type 2 should be advised of this high early rate of asymptomatic shedding and of potential transmission to sexual partners. PMID- 1310838 TI - Delay by internists in obtaining diagnostic biopsies in patients with suspected cancer. AB - OBJECTIVE: To investigate the degree and type of delays in performing diagnostic biopsies in medical patients with suspected malignancy. DESIGN: Retrospective survey of clinical histories of patients referred between January 1985 and March 1989. SETTING: Inner city teaching hospital internal medicine (non-oncologic) services. PATIENTS: Patients with gastrointestinal and lung cancers, adenocarcinoma of unknown primary site, and lymphomas were referred as inpatients by internists. Two hundred fifty-five patients were eligible, and 177 were evaluable. MAIN OUTCOME MEASURES: The number, type, and results of tests done before and after biopsy were analyzed. RESULTS: In 67% of patients the biopsied lesion was detected by the second day of evaluation; however, there was an 8- to 10-day delay before a biopsy was done. This delay was consistent across the four malignancy groups studied. Although logistic and other unavoidable delays occurred in 40% of the cases, in 60% delays could only be attributed to continued, frequently low yield, noninvasive tests. An average of 3.3 tests were made per patient, with only 24% leading to a definitive biopsy. CONCLUSION: Because of the performance of many other tests, a substantial delay exists in proceeding to biopsy during the diagnosis of cancer by internists. PMID- 1310839 TI - New macrolide antibiotics: azithromycin and clarithromycin. PMID- 1310840 TI - Itraconazole-digoxin interaction. PMID- 1310841 TI - In situ hybridization and laryngeal papillomas. AB - The technique of in situ hybridization with biotin-labeled probes was applied to 20 patients with laryngeal papillomatosis (9 with adult-onset disease and 11 with juvenile-onset). Ten patients were noted for epithelial transformation of their laryngeal disease. All patients, regardless of their clinical outcome, tested positive for human papillomavirus group 6/11. The biotin method of in situ hybridization proved to be a sensitive method in this study, identifying the infecting viral group in 23 of 24 samples. This study also tested for group 16/18 and is the first to test for the presence of group 31/33/35 in the larynx. These viruses or members of related groups have been reported in malignancies of the head and neck as well as the uterine cervix. They have yet, however, to be identified in benign laryngeal papillomas or laryngeal papillomas that have undergone epithelial transformation. PMID- 1310843 TI - Glomus tumor of the nail. A 'red herring' clarified by magnetic resonance imaging. PMID- 1310842 TI - Angiotensin-1-converting enzyme activity as index of pulmonary damage in thermal injury with or without smoke inhalation. AB - Serum angiotensin-converting enzyme (ACE) activity, plasma renin activity (PRA), and serum aldosterone levels were measured up to four weeks in a population of adults exposed to thermal injury, with or without concomitant exposure to smoke inhalation. In 10 patients, plasma levels of angiotensin-2 and ACE activity in bronchial lavage were also evaluated. Patients with severe burn injury had a significant decline of serum ACE activity while the concentrations of aldosterone and PRA were markedly elevated. Smoke inhalation seemed to counterbalance the decline of serum ACE activity, and, in the last group of patients, ACE concentrations were higher than those recorded in patients suffering only from cutaneous burn. The ACE activity was evidenced in bronchial lavage of patients exposed to smoke inhalation with the highest values present in the first day after the injury. The same patients had also very elevated levels of plasma angiotensin 2. In conclusion, serum ACE activity decreases in burn patients according to the severity of the cutaneous burn; smoke inhalation influences serum levels of the enzyme with concentration values opposite to the low ones present in cutaneous burn. Finally, the enzyme activity has an independent pattern from that of the other components of the renin angiotensin aldosterone system. The evaluation of ACE activity may be a marker of pulmonary damage in smoke inhalation. PMID- 1310845 TI - Long term survival after heart transplantation for doxorubicin induced cardiomyopathy. PMID- 1310844 TI - Epstein-Barr virus-related persistent erythema multiforme in chronic fatigue syndrome. AB - BACKGROUND: Erythema multiforme (EM) has been rarely reported in Epstein-Barr virus (EBV)-associated diseases; this includes patients with chronic fatigue syndrome who have chronic or recurrent and disabling illness and an abnormal antibody reactivity to EBV. We describe a patient fulfilling the chronic fatigue syndrome diagnostic criteria who had developed an unusually persistent EM resistant to corticosteroids therapy. The EBV DNA was studied in skin EM lesions, throat washings, peripheral mononuclear cells, and plasma. The EBV antigens were studied in skin EM lesions and in mononuclear cells. The patient was followed up to 2 years. OBSERVATIONS: The patient had abnormal titers of antibodies against various EBV antigens and by immunofluorescence she disclosed the EBV nuclear antigen and the viral capsid antigen in the blood vessels of the affected skin. The dot blot hybridization assay detected viral DNA in throat washings and mononuclear cells, but not in plasma. The presence of the viral genomic content in lesional skin is suggested by the autoradiographic signal and by the difference from appropriate control specimens. Skin lesions and constitutional symptoms cleared after acyclovir sodium therapy and recurred after discontinuation of this therapy. CONCLUSIONS: This is the first EM case in which evidence of the EBV causal role has been provided. The association with chronic fatigue syndrome suggests the EBV role in selected cases of this syndrome. PMID- 1310846 TI - Serum angiotensin-converting enzyme level is elevated in patients with human immunodeficiency virus infection. AB - BACKGROUND: Serum angiotensin-converting enzyme (ACE) level is elevated in a number of disease states and medical conditions. Based on review of the medical literature, we postulated that serum ACE level elevation may occur during infection with the human immunodeficiency virus (HIV). METHODS: In a prospective, controlled study, serum ACE levels of HIV-positive patients were compared with those of an HIV-negative control population. RESULTS: Serum ACE levels were significantly elevated in patients with the acquired immunodeficiency syndrome (55.4 +/- 11.4 U/L) and in patients with an intermediate stage of HIV infection (57.2 +/- 25.3 U/L) when compared with levels in controls (31.9 +/- 14.0 U/L). CONCLUSIONS: Elevated serum ACE levels occur in HIV infection and may be an important marker for this disease. PMID- 1310847 TI - APUDomas: acute complications and their medical management. AB - APUDomas are rare tumours originating from a variety of endocrine cells localized in different organs. Acute complications from APUDomas usually result from the increased biosynthesis and release of bioactive amines or polypeptide hormones by the tumour. Less frequently, bleeding or compression by the tumour can occur requiring emergency surgery. Increased gastrin production by gastrinomas is the cause of ZES (peptic ulceration and diarrhoea) by gastrin effects on gastric acid secretion. Volume depletion, hypokalaemia, severe bleeding, duodenal perforation, oesophageal stricture and pyloric stenosis are the most dramatic complications. Treatment of these complications and their prevention has been facilitated by the availability of antagonists to H2 receptors and H(+)-K+ proton pump. These medications should control acid output in every patient with ZES. Frequent manifestations of carcinoid tumours, VIPomas and medullary thyroid carcinomas are flushing and diarrhoea. Octreotide, a long-acting somatostatin analogue, has markedly changed the management of these patients, their symptoms decreasing in severity or disappearing in most cases. Octreotide has also been used with success in the prevention and treatment of the carcinoid crisis, a dreaded complication of carcinoid tumours. A better understanding of the pathophysiology of APUDomas has enabled new treatment designs which have considerably ameliorated the quality of life of patients affected by these tumours; efforts must be continued to affect their life expectancy. PMID- 1310848 TI - Endotoxin-inducible cytotoxicity in liver cell cultures--II. Demonstration of endotoxin-tolerance. AB - Endotoxins from gram negative bacteria, central mediators of septic shock, share the characteristic property of inducing tolerance against their own action. This work investigates whether a corresponding ex-vivo tolerance can be observed in a cellular system with endotoxin-inducible hepatocytoxicity. The following experimental approaches were chosen in order to induce an endotoxin-unresponsive state prior to cell preparation: (1) pretreatment of rats with endotoxin, (2) partial hepatectomy, (3) use of neonatal rats and (4) pretreatment of rats with silica. An in-vivo protection against endotoxin-induced liver injury was obtained by all of these four measures: cells prepared from these groups of animals showed greatly diminished sensitivity towards endotoxin-induced hepatocytotoxicity in vitro. The suppressed endotoxin sensitivity after silica pretreatment was partially restored in vitro by the addition of native Kupffer cells (KC). Isolated KC of all but the endotoxin-pretreated animals secreted tumor necrosis factor-alpha in response to endotoxin. It is concluded that different types of tolerance can be distinguished: (a) impairment of macrophage functions (silica pretreatment), (b) hepatocyte unresponsiveness (neonatal rats and hepatectomy) and (c) impaired macrophage function combined with hepatocyte unresponsiveness (endotoxin-pretreated rats). PMID- 1310849 TI - Effects of calcium and calcium-channel blocker methoxyverapamil on the beta adrenoceptors in myocardial cells in vitro. AB - The possible relationship between methoxyverapamil (D600) as a calcium-channel blocker and the beta-adrenoceptors was investigated on heart cells grown in culture, using [3H]CGP-12177 as a radioligand. Treatment with D600 (20 micrograms/mL) for 24 hr caused a decrease of 30% in the [3H]CGP-12177 binding sites. Scatchard analysis showed that the Bmax is similar in control and D600 treated cells, but the Kd in D600-treated cells increases. The effect of D600 on the isoproterenol-induced adenylate cyclase activation was examined and it was found that the D600 prevented the increase in cAMP obtained by isoproterenol treatment. These results indicate that the action of D600 on the beta adrenoceptors is a competitive inhibition of the [3H]CGP-12177 binding sites. We investigated the effect of Ca2+ in the growth medium on the level of beta adrenoceptors. Heart cells grown for 24 hr in Ca(2+)-free medium showed a decrease of 36% in the [3H]CGP-12177 binding sites without changing the dissociation constant. This decrease is probably a result of reduction in synthesis of the receptors. The level of receptors returned to control values following replenishment with normal growth medium. These results show that calcium is essential for the development of the beta-adrenoceptors in heart cells in vitro. PMID- 1310850 TI - Evidence that the loss of rat liver cytochrome P450 in vitro is not solely associated with the use of collagenase, the loss of cell-cell contacts and/or the absence of an extracellular matrix. AB - Two methods avoiding the widespread technique of collagenase perfusion have been employed to study the regulation of total cytochrome P450 content in rat hepatocyte culture. One technique required the perfusion of the liver with the chelating agent EDTA to dissociate the parenchymal cells prior to culture. Over a period of 48 hr, cultured hepatocytes isolated by EDTA perfusion showed comparable losses of cytochrome P450 as cells isolated by perfusion with collagenase. The second technique involved the culture of 210-240 microns thick "precision cut" liver slices. The results presented here indicate that the liver slices remain viable for 24 hr of culture, but that liver slices also lose their cytochrome P450 content at a comparable rate to collagenase prepared cells in culture. Collectively the results suggest that there is not a direct causal relationship between the loss of cytochrome P450 and one or a combination of the use of collagenase; the loss of cell-cell contacts and the absence of an extracellular matrix. PMID- 1310851 TI - Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylates. Direct evaluation with electron spin resonance spectroscopy. AB - Reactive oxygen radicals such as superoxide and hydroxyl radicals, as well as intermediate unsaturated fatty acid radicals, have been proposed as playing an important role in various diseases including inflammatory bowel disease (IBD). In this study we evaluated radical scavenger properties of aminosalicylates used in the therapy of IBD using spin trapped electron spin resonance spectroscopy. 5 Aminosalicylic acid (5-ASA), 4-aminosalicylic acid and olsalazine had superoxide radical scavenger properties (IC50 = 0.4, 0.4 and 1.0 mM, respectively). 5-ASA and benzalazine also inhibited hydroxyl radicals (IC50 = 6.5 mM). Fatty acid radicals were not inhibited by aminosalicylates. Our results support the hypothesis that therapeutically active compounds may be oxygen radical scavengers and that fatty acid radical scavenging has to be performed by drugs other than aminosalicylates. PMID- 1310852 TI - Dicentrine, a novel antiplatelet agent inhibiting thromboxane formation and increasing the cyclic AMP level of rabbit platelets. AB - Dicentrine is an antiplatelet agent isolated from the Chinese herb Lindera megaphylla. We examined the in vitro effects of dicentrine on various aspects of platelet reactivity. Dicentrine inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA), collagen, ADP, platelet activating factor (PAF), thrombin and U46619. Dicentrine also inhibited the thromboxane B2 formation caused by AA, collagen and thrombin in washed intact platelets or that induced by AA in lysed platelet homogenate, while prostaglandin D2 formation caused by AA was not increased. The generation of inositol monophosphates (in the presence of indomethacin) caused by thrombin, collagen and PAF was not suppressed significantly, nor did dicentrine suppress fibrinogen induced aggregation of elastase-treated platelets. Dicentrine inhibited the intracellular Ca2+ increase in quin-2/AM-loaded platelets caused by thrombin, PAF, collagen and AA. The cyclic AMP level was elevated by dicentrine in a concentration-dependent manner. These data indicate that the inhibitory effect of dicentrine on platelet aggregation and ATP release was due to the inhibition of thromboxane formation and the elevation of the level of cyclic AMP. PMID- 1310853 TI - Components of intrinsic drug resistance in the rat hepatoma. AB - A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell. PMID- 1310854 TI - One-electron reductive bioactivation of 2,3,5,6-tetramethylbenzoquinone by cytochrome P450. AB - Bioreductive activation of quinones in mammalian liver has generally been attributed to NADPH-cytochrome P450 reductase. However, in view of the 20-30-fold molar excess of cytochrome P450 over NADPH-cytochrome P450 reductase on the endoplasmic reticulum of the rat liver cell and the capability of cytochrome P450 to bind and reduce xenobiotics, it was considered of interest to investigate the possible role of cytochrome P450 in the bioreduction of quinones. In the present study, 2,3,5,6-tetramethyl-1,4-benzoquinone (TMQ) was chosen as a model quinone. First, TMQ was found to bind at the metabolic active site of phenobarbital (PB) inducible cytochrome P450s of rat liver microsomes, indicating that TMQ is a potential substrate for cytochrome P450-mediated biotransformation. Second, with electron spin resonance, one-electron reduction of TMQ to a semiquinone free radical (TMSQ) was found to occur in these microsomal fractions. SK&F 525-A, a well-known inhibitor of cytochrome P450, strongly inhibited TMSQ formation in these subcellular fractions without affecting NADPH-cytochrome P450 reductase activity. One-electron reductive bioactivation of TMQ was further investigated with purified NADPH-cytochrome P450 reductase alone and in reconstituted systems of purified cytochrome P450-IIB1 and NADPH-cytochrome P450 reductase. As measured by ESR, purified cytochrome P450-IIB1 in the presence of NADPH-cytochrome P450 reductase was able to reduce TMQ to TMSQ at a much greater rate than in the presence of NADPH-cytochrome P450 reductase alone. Reduction of TMQ was also investigated by measuring the initial rate of NADPH oxidation by TMQ under anaerobic conditions. Inhibitors of cytochrome P450, namely SK&F 525-A and antibodies against PB-inducible cytochrome P450s, caused a substantial decrease in reductive metabolism in PB-treated microsomes. These antibodies were also effective in the inhibition of TMQ-induced NADPH oxidation in a complete reconstituted system of equimolar concentrations of cytochrome P450-IIB1 and NADPH-cytochrome P450 reductase, indicating that the reaction was specific for cytochrome P450-IIB1. Finally, initial rates of NADPH oxidation were determined in reconstituted systems containing varying amounts of NADPH-cytochrome P450 reductase and cytochrome P450-IIB1 to determine the contribution of either enzyme in the reduction of TMQ. As expected, NADPH-cytochrome P450 reductase was able to reduce TMQ to a small extent. However, reconstitution in the presence of increasing amounts of cytochrome P450-IIB1 (relative to NADPH-cytochrome P450 reductase) resulted in increasing rates of TMQ-induced NADPH oxidation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1310855 TI - Guinea pig whole blood 5-lipoxygenase assay: utility in the assessment of potential 5-lipoxygenase inhibitors. AB - Guinea pigs are widely used in the study of the role of leukotrienes in airway pathophysiology. Extensive research efforts have utilized this species in the development of potential therapeutic agents associated with inhibition of leukotriene production (e.g. 5-lipoxygenase inhibitors and 5-lipoxygenase activating protein antagonists) for the treatment of acute bronchospasm in asthma. We now report, for the first time, an ex vivo whole blood 5-lipoxygenase assay in guinea pigs which should prove useful in the future development of leukotriene biosynthesis inhibitors. Addition of 150 microM arachidonic acid (AA) to heparinized whole blood for 5 min prior to the stimulation with 20 micrograms/mL A23187 resulted in a 10-fold increase in leukotriene B4 (LTB4; 11.36 +/- 1.55 ng/mL) above basal (0.96 +/- 0.29 ng/mL) within 10 min. To further validate the utility of the assay, we utilized the 5-lipoxygenase inhibitor BW A4C. Pretreatment of guinea pig whole blood with BW A4C in vitro prior to stimulation resulted in a concentration-dependent inhibition of LTB4 production (IC50 = 229 nM), whereas thromboxane B2 (TXB2) production was unaffected. Likewise, when BW A4C was administered to guinea pigs intravenously (3 mg/kg), we observed a rapid and marked (approximately 90%) reduction in whole blood LTB4 production which returned to control (pre-drug values) by 5 hr. In contrast, TXB2 production was unaffected over the same experimental time period. In summary, we have described a whole blood assay which can discriminate 5-lipoxygenase inhibitors both in vitro and in vivo. Furthermore, this assay system will be of use in determining the potency, efficacy, selectivity, and pharmacodynamic properties of 5-lipoxygenase inhibitors in guinea pigs. PMID- 1310856 TI - Modulation of superoxide production from murine macrophages by the antitumour agent flavone acetic acid and xanthenone acetic acid analogues. PMID- 1310857 TI - Sequence alignment of the G-protein coupled receptor superfamily. AB - The multitude of G-protein coupled receptor (GPR) superfamily cDNAs recently isolated has exceeded the number of receptor subtypes anticipated by pharmacological studies. Analysis of the sequence similarities and unique features of the members of this family is valuable for designing strategies to isolate related cDNAs, for developing hypotheses concerning substrate-ligand and receptor-effector interactions, and for understanding the evolution of these genes. We have compiled and aligned the 74 unique amino acid sequences published to date and review the present understanding of the structural motifs contributing to ligand binding and G-protein coupling. PMID- 1310858 TI - Cloning and characterization of the human insulin-like growth factor-I receptor gene 5'-flanking region. AB - The insulin-like growth factor-I receptor (IGFIR) is a membrane-bound glycoprotein that mediates the action of insulin-like growth factors. The cDNAs for the human IGFIR have been cloned and expressed, but the structures of the gene and its promoter have not been elucidated. In this study, we isolated an IGFIR promoter clone from a human chromosome 15 library. This clone contained the promoter, first exon, and a portion of the first intron. Sequence analysis of the 5' region that contained the promoter revealed that it lacked both TATA and CAAT boxes. The promoter contained binding sites for the transcription factors Sp1, AP 2, and the epidermal growth factor receptor transcription factor (ETF). Primer extension analysis of IGFIR mRNA indicated the presence of a single transcription start site 1,012 bp upstream from the ATG. When the putative promoter was ligated into a promoterless CAT vector and transfected mto HEPG2 cells, CAT activity was expressed, indicating that promoter activity was contained in this fragment. Other constructs containing the promoter and portions of the 5' untranslated region were used in transfection studies, and indicated that the 5' untranslated regions may play a role in promoter activity. Comparison of the human IGFIR promoter with that of the rat IGFIR promoter revealed significant sequence homology. Comparison of the IGFIR promoter with that of the human insulin receptor (IR) revealed structural similarities, although the arrangement of promoter elements differed. PMID- 1310859 TI - The cloned promoter of the human DNA beta-polymerase gene contains a cAMP response element functional in HeLa cells. AB - The mammalian DNA beta-polymerase (beta-pol) gene is constitutively expressed in cultured cells as a function of growth stage and DNA replication, but is expressed in rodents in a tissue-specific fashion. As revealed by transient expression experiments with wild-type and mutated beta-pol promoter fusion genes, the cloned human beta-pol promoter is transcriptionally regulated by signals acting through the single palindromic sequence (GT-GACGTCAC) known as an ATF/CRE binding site centered at position -45 in the core promoter. Although the mere presence of the ATF/CRE palindromic sequence in a promoter does not always confer cAMP responsiveness or protein binding over and around the ATF/CRE sequence, we find that agents that increase cAMP levels (forskolin and IBMX) in HeLa cells activate the beta-pol promoter; activation also can be observed by coexpression of the protein kinase A catalytic subunit. Experiments with mutagenized beta-pol promoters indicate that the ATF/CRE-binding site mediates these effects. Thus, the ATF/CRE-binding site in the context of this TATA-less constitutive promoter is able to respond to the kinase A signal transduction pathway. PMID- 1310860 TI - Electrodiagnostic characteristics of Wegener's granulomatosis-associated peripheral neuropathy. AB - Wegener's granulomatosis is a multisystem disease distinguished by a triad of necrotizing granulomatous vasculitis involving the upper and lower respiratory tracts, glomerulonephritis and systemic, small vessel vasculitis. The latter can cause neurologic manifestations when the vasa nervorum are affected. A 53-yr-old male presented with a 3-mo history of chronic nasal congestion, arthralgias, pruritic maculopapular eruption, epistaxis and lower extremity weakness. Subsequent lung and chest wall biopsies confirmed diagnosis of Wegener's granulomatosis. Summary of electrodiagnostic data obtained on initial presentation and comparison with later study indicated a sensorimotor polyneuropathy with wide-spread axonal involvement noted particularly in the distal lower extremity musculature. Electrodiagnostic documentation of rapid progression proved useful in directing alteration of immunosuppressive therapy, with favorable clinical and functional outcome. We believe this is the second case presented of a patient with documented Wegener's granulomatosis and overt clinical evidence of poly-neuropathy in whom both electroneurographic and electromyographic studies are described. Electrodiagnostic results are presented with discussion of pertinent literature. PMID- 1310861 TI - Primary structure and expression of the gamma 2 subunit of the glutamate receptor channel selective for kainate. AB - The presence and primary structure of a novel subunit of the mouse glutamate receptor channel, designated as gamma 2, have been revealed by cloning and sequencing the cDNA. The gamma 2 subunit has structural characteristics common to the neurotransmitter-gated ion channel family and shares a high amino acid sequence identity with the rat KA-1 subunit, thus constituting the gamma subfamily of the glutamate receptor channel. Expression of the gamma 2 subunit together with the beta 2 subunit in Xenopus oocytes yields functional glutamate receptor channels selective for kainate. PMID- 1310862 TI - Possible role during exocytosis of a Ca(2+)-activated channel in neurohypophysial granules. AB - Ion channels from bovine neurohypophysial granules were incorporated into artificial lipid bilayers. The larger amplitude channel is permeable to cations and exhibits multiple conductances. The channel opens only in the presence of free Ca2+, but is inhibited by relatively high Ca2+ concentrations. Release of vasopressin from permeabilized neurohypophysial terminals also shows a similar biphasic dependence on Ca2+. Release is selectively inhibited by low concentrations of the long-chain alcohol octanol, but not by high concentrations of ethanol, as is the neurosecretory granule Ca(2+)-activated cation channel. Furthermore, Ca(2+)-evoked release and channel activity are both inhibited by the long-chain tetraethylammonium analogs decamethonium and decyl-triethyl ammonium bromide. The close correlation between channel and release properties lead us to conclude that the Ca(2+)-activated channel is involved in peptide secretion. PMID- 1310863 TI - Nicotinic receptors that bind alpha-bungarotoxin on neurons raise intracellular free Ca2+. AB - Many populations of vertebrate neurons have a membrane component that binds alpha bungarotoxin and cholinergic ligands. Despite the abundance of this component and its similarities to nicotinic receptors, its function has remained controversial. Using a fluorescence assay, we show here that activation of the component elevates the intracellular concentration of free Ca2+, demonstrating a receptor function for the toxin-binding component. Whole-cell voltage-clamp and intracellular recordings did not detect a significant current resulting from receptor activation, possibly because the currents were small or the receptors rapidly desensitized. The rise in intracellular free Ca2+ caused by the receptor was prevented by Ca2+ channel blockers. This suggests a signaling cascade likely to have important regulatory consequences for the neuron. PMID- 1310864 TI - Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors. AB - The mechanism by which thrombin induces neurite retraction was studied in NB2a mouse neuroblastoma cells. The rapid effect of thrombin (completed within minutes) appears to involve an interaction between its anion-binding exosite and the thrombin receptor. Structural alterations of this site increase the EC50 for thrombin-mediated retraction, and a hirudin C-terminal peptide that blocks this site inhibits the response. The thrombin effect was mimicked by a 14 amino acid peptide starting with Ser-42, at the proposed cleavage site of the human thrombin receptor. The protein kinase inhibitors staurosporine and H-7 blocked thrombin induced retraction. It is therefore proposed that thrombin-mediated neurite retraction is caused by cleavage-induced activation of the thrombin receptor and involves stimulation of a protein kinase(s). PMID- 1310865 TI - A regulatory subunit of the cAMP-dependent protein kinase down-regulated in aplysia sensory neurons during long-term sensitization. AB - Binding of cAMP by the five neuronal isoforms (N1-5) of the regulatory (R) subunit of the Aplysia cAMP-dependent protein kinase is diminished in sensory neurons stimulated to produce long-term presynaptic facilitation. To determine how the cAMP-binding activity of the R subunits is lost, we isolated cDNAs encoding N4, which is a homolog of mammalian RI. Immunoblots with antisera raised against the R protein overexpressed in E. coli show that the diminished binding activity, which occurs in long-term facilitation, results from coordinate loss of R protein isoforms. No change was detected in the amount of transcripts for R subunits, suggesting that the down-regulation results from enhanced proteolytic turnover. PMID- 1310866 TI - ANA says AIDS guidelines are sound. PMID- 1310867 TI - The role of human papillomavirus in cutaneous neoplasia. PMID- 1310868 TI - Growth factors in cutaneous biology and disease. PMID- 1310869 TI - Regulation of the plasminogen activator system in non-small cell lung cancer cell lines by growth factors EGF, TGF-alpha and TGF-beta. PMID- 1310870 TI - Differential expression of glutamate receptor genes (GluR1-5) in the rat retina. AB - The recent isolation of at least five different cDNAs encoding functional subunits of glutamate receptors (GluR1 to GluR5) has revealed a diversity whose function is not understood. To learn more about how these different receptor subunits are used in the brain, we undertook an in situ hybridization study of the retina to define how the different glutamate receptor genes are expressed. We chose the retina because the glutamate sensitivities of its different cell types have been characterized, and these different neurons reside in different laminae. Hybridization of [35S]UTP-labeled cRNA probes with transverse sections and freshly dissociated cells reveals that all five receptor subunits are expressed in the retina. Hybridization signal is detected in different, but overlapping, sets of cells in the retina. GluR1, GluR2, and GluR5 are expressed by many somata, and GluR4 by a few, in the outer third of the inner nuclear layer, where the horizontal cells reside. Transcripts for GluR1, GluR2, and GluR5 are found in the somata within the middle third of the inner nuclear layer, which is where the bipolar cell somata are located, and GluR2 probes label freshly dissociated rod bipolar cells. All of the probes produce labeling over the cells at the inner edge of the inner nuclear layer, which are probably amacrine cells, as well as over the cell bodies in the ganglion cell layer. PMID- 1310871 TI - Localization of GABAA receptor subtypes in the tiger salamander retina. AB - Dry autoradiography was used to determine the distribution of GABAA binding sites in tiger salamander retina. High-affinity binding of [3H]-flunitrazepam [( 3H] FNZ) was used to localize benzodiazepine receptors (BZR) and [3H]-muscimol was used to localize the GABAA recognition site. Specific [3H]-FNZ binding was present only in the inner retina, primarily in the inner plexiform layer (IPL). Co-incubation with GABA enhanced [3H]-FNZ binding by 20-50%. [3H]-muscimol binding was found throughout the IPL and in the outer plexiform layer (OPL). Mouse monoclonal antibodies 62-3G1 and BD-17, that recognize the GABAA beta 2, beta 3 polypeptides, and BD-24, that recognizes the GABAA alpha 1 polypeptide, did not label either the OPL or IPL, despite numerous variations in the fixation and immunoprocessing methods. GABAA receptor location, as revealed by [3H] muscimol binding, matches the distribution of presumed GABAergic terminals in the OPL and IPL. We suggest that there are at least two subtypes of GABAA receptor in the tiger salamander retina: one type is present only in the inner retina, primarily in the IPL and is functionally coupled to BZRs; the other type is located in the OPL and is not coupled to the BZRs. Furthermore, GABAA receptors in the tiger salamander retina appear to be of a different epitope than GABAA receptors in numerous other preparations that are recognized by mAbs 62-3G1, BD 17, and BD-24. PMID- 1310872 TI - The c-type cytochromes of methylotrophic bacteria. PMID- 1310873 TI - Multifrequency EPR investigations into the origin of the S2-state signal at g = 4 of the O2-evolving complex. AB - The low-temperature S2-state EPR signal at g = 4 from the oxygen-evolving complex (OEC) of spinach Photosystem-II-enriched membranes is examined at three frequencies, 4 GHz (S-band), 9 GHz (X-band) and 16 GHz (P-band). While no hyperfine structure is observed at 4 GHz, the signal shows little narrowing and may mask underlying hyperfine structure. At 16 GHz, the signal shows g-anisotropy and a shift in g-components. The middle Kramers doublet of a near rhombic S = 5/2 system is found to be the only possible origin consistent with the frequency dependence of the signal. Computer simulations incorporating underlying hyperfine structure from an Mn monomer or dimer are employed to characterize the system. The low zero field splitting (ZFS) of D = 0.43 cm-1 and near rhombicity of E/D = 0.25 lead to the observed X-band g value of 4.1. Treatment with F- or NH3, which compete with Cl- for a binding site, increases the ZFS and rhombicity of the signal. These results indicate that the origin of the OEC signal at g = 4 is either an Mn(II) monomer or a coupled Mn multimer. The likelihood of a multimer is favored over that of a monomer. PMID- 1310874 TI - Rates of interactions of superoxide with vitamin E, vitamin C and related compounds as measured by chemiluminescence. AB - The rate constants for the interactions of superoxide with vitamin E (alpha tocopherol), vitamin C (ascorbic acid) and their related compounds have been measured by a chemiluminescence method. A strong chemiluminescence of a constant intensity was observed when xanthine oxidase was added to an aqueous solution of hypoxanthine and a Cypridina luciferin analog, 2-methyl-6-phenyl-3-7 dihydroimidazo[1,2-a]pyrazin-3-one (CLA). Vitamin E, vitamin C and their related compounds competed with CLA to react with superoxide and reduced the chemiluminescence intensity. From a kinetic analysis of the effect of addition of these compounds on the chemiluminescence intensity, the rate constants for their interactions with superoxide were measured at 25 degrees C and pH 7.8. The rate constants were obtained as 3.3 x 10(5) and 1.7 x 10(4) M-1 s-1 for ascorbate and 2-carboxy-2,5,7,8-tetramethyl-6-chromanol, respectively, and also as 4.9 x 10(3) and 4.5 x 10(3) M-1 s-1 for alpha-tocopherol incorporated into soybean and dimyristoyl phosphatidylcholine liposomal membranes, respectively. It has been shown that this method is a sensitive and a quick method which can be applied for measurement of the reactivities of various natural and synthetic compounds toward superoxide. In addition it has been shown that this method can also be applied to the heterogeneous system as well as homogeneous solution, which makes it more versatile and useful for the study in biochemistry. PMID- 1310875 TI - Polyphosphoinositide phospholipase C in wheat root plasma membranes. Partial purification and characterization. AB - The effect of various detergents on polyphosphoinositide-specific phospholipase C activity in highly purified wheat root plasma membrane vesicles was examined. The plasma membrane-bound enzyme was solubilized in octylglucoside and purified 25 fold by hydroxylapatite and ion-exchange chromatography. The purified enzyme catalyzed the hydrolysis of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) with specific activities of 5 and 10 mumol/min per mg protein, respectively. Phosphatidylinositol (PI) was not a substrate. Optimum activity was between pH 6-7 (PIP) and pH 6-6.5 (PIP2). The enzyme was dependent on micromolar concentrations of Ca2+ for activity, and millimolar Mg2+ further increased the activity. Other divalent cations (4 mM Ca2+, Mn2+ and Co2+) inhibited (PIP2 as substrate) or enhanced (PIP as substrate) phospholipase C activity. PMID- 1310876 TI - Diacylglycerol kinase in plasma membranes from wheat. AB - Diacylglycerol kinase activity was demonstrated in highly purified plasma membranes isolated from shoots and roots of dark-grown wheat (Triticum aestivum L.) by aqueous polymer two-phase partitioning. The active site of the diacylglycerol kinase was localized to the inner cytoplasmic surface of the plasma membrane using isolated inside-out and right-side-out plasma membrane vesicles from roots. The enzyme activity in plasma membrane vesicles from shoots showed a broad pH optimum around pH 7. The reaction was Mg2+ and ATP dependent, and maximal activity was observed around 0.5 mM ATP and 3 mM MgCl2. The Mg2+ requirement could be substituted only partially by Mn2+ and not at all by Ca2+. The phosphorylation of endogenous diacylglycerol was strongly inhibited by detergents indicating an extreme dependence of the lipid environment. Inositol phospholipids stimulated the activity of diacylglycerol kinase in plasma membranes from shoots and roots, whereas the activity was inhibited by R59022, a putative inhibitor of several diacylglycerol kinase isoenzymes involved in uncoupling diacylglycerol activation of mammalian protein kinase C. PMID- 1310877 TI - Photoaffinity cross-linking of acyl carrier protein to Escherichia coli membranes. AB - Acyl Carrier Protein (ACP) is a small acidic protein which interacts with the various enzymes implicated in the biosynthesis of fatty acids in E. coli. It also interacts with the inner membrane proteins implicated in the biosynthesis of phospholipids. Samples of radioactive ACP were prepared with high specific activities and bearing photoactivable aryl azide derivatives. Two photoactivable reagents were used: para azido phenacyl bromide (pAPA) which reacts with the SH of the ACP prosthetic group and the N-hydroxysuccinimide ester of 4-azido salicylic acid (NHS-ASA) which reacts with the amino groups of the protein. Various methods were used to demonstrate that ACP could be cross-linked specifically to an inner membrane protein of E. coli, most probably to the glycerol-3-phosphate acyl transferase (GPAT). This covalent link should provide a powerful tool for further analysis of the structure of GPAT and its role in phospholipid biosynthesis. These photoactivable aryl azide derivatives of ACP could also be very useful for studying the interaction of ACP with the soluble enzymes implicated in fatty acid biosynthesis. PMID- 1310879 TI - Heparin-associated thrombocytopenia: successful therapy with the heparinoid Org 10172 in a patient showing cross-reaction to LMW heparins. AB - A patient suffering from heparin-associated thrombocytopenia (HAT), recurrent arteriothromboses, and acute renal failure after treatment with standard heparin is described. He failed to improve when therapy was continued with low-molecular weight (LMW) heparin (Fragmin, Kabi Pfrimmer, Erlangen, FRG). By means of the in vitro heparin-induced platelet activation (HIPA) assay it was shown that standard heparin and the LMW heparins Fragmin and Fraxiparin (Sanofi Labaz, Munich, FRG), as well as the enoxaparine Clexane (Nattermann, Cologne, FRG), all induced platelet activation with the patient's serum. In contrast, the LMW heparinoid Org 10172 (Organon, Oss, The Netherlands) did not cause platelet activation. When the patient was subsequently treated by parenteral administration of Org 10172 as anticoagulant over a period of several weeks the number of platelets rapidly increased and the patient almost completely recovered. This case shows that strong in vivo and in vitro cross-reactivity between standard heparin and LMW heparins may occur, but can be avoided by the use of a novel heparinoid, Org 10172. The HIPA assay provides a simple and sensitive laboratory method for the choice of an innocuous heparin or heparinoid for continued parenteral anticoagulation. PMID- 1310878 TI - Factor IXi-antithrombin (IXiAT) and thrombin-antithrombin (TAT) complexes in lung cancer patients. AB - Coagulation activation frequently occurs in cancer patients, resulting in thromboembolic complications and/or intravascular coagulation activation. The mechanisms leading to these alterations still are poorly understood. One explanation for the coagulation activation in malignant diseases is the presence of a direct factor X-activating cancer procoagulant. Coagulation activation in lung cancer patients develops at earlier stages than factor X activation; we demonstrated increased factor IXiAT complexes in addition to elevated TAT complexes. The increases of factor IXiAT complexes were not dependent upon the stage of the disease. In contrast, TAT complexes were higher in patients suffering from advanced pulmonary non-small cell carcinoma than in patients with limited disease. In conclusion, coagulation activation in pulmonary cancer patients occurs at earlier steps in the coagulation cascade than factor X activation. While this activation is not dependent upon the stage of the disease, the observation that TAT complexes showed higher elevations in patients with advanced than in those with limited pulmonary non-small cell carcinoma could be an indication of a cancer procoagulant that directly activates factor X. PMID- 1310880 TI - Hepatocellular carcinoma. PMID- 1310881 TI - Peripheral nerve injuries in children with traumatic brain injury. AB - The relationship between traumatic brain injuries and associated peripheral nerve injuries has not been previously studied in children in the rehabilitation setting. One hundred and fifty-seven consecutive admissions of brain-injured children were included in this prospective study to determine the frequency and pattern of recovery of peripheral nerve injuries in such patients. Twelve patients met the clinical diagnostic criteria for peripheral nerve injury. Electrodiagnostic studies confirmed the clinical diagnosis in 11 (7%) patients. Grading of spontaneous activity and electrodiagnostic study of the contralateral limb were used to differentiate electromyographic abnormalities due to upper motor neuron lesion and nerve injury. Electrodiagnostic study was useful to confirm clinical diagnosis and predict prognosis of nerve injuries. Two patients developed preventable pressure neuropathy. Eight patients showed moderate or full recovery in 9-10 months post-injury. All children with severe brain injuries should be evaluated for concomitant peripheral nerve injuries. PMID- 1310882 TI - Differential effects of parathyroid hormone on chick growth plate and articular chondrocytes. AB - Parathyroid hormone (PTH) binds specifically to the hypertrophic region of growth plate cartilage [16]. This specific binding suggests a role for this hormone in chondrocyte maturation. Enzymatically isolated chick articular and growth plate chondrocytes grown in monolayer culture were used to assay the direct effects of PTH on chondrocytes. The articular chondrocytes were unresponsive to PTH. The growth plate chondrocytes, however, demonstrated a marked mitogenic response to PTH, with a 39-fold increase of [3H]-thymidine incorporation into DNA. PTH also affected matrix production by the growth plate chondrocytes causing a twofold stimulation of proteoglycan synthesis as determined by the rate of 35SO4 incorporated into matrix macromolecules. Furthermore, PTH depressed collagen synthesis as measured by [3H]-proline incorporation. PTH caused a 12-fold increase in intracellular cAMP in growth plate chondrocytes but no increase in the articular cells. This specificity of PTH for growth plate chondrocytes suggests a possible regulatory role in enchondral ossification. PMID- 1310884 TI - Cancer in children. AB - Cancer is a relatively unusual disease entity in children. However, its diagnosis often proves devastating for the families of afflicted youngsters. The types of cancer seen in children are very different from those found in adults. Primarily, they include leukemias, lymphomas and brain tumors. In most cases, the cause(s) of these cancers is unknown. Standard treatment modalities include surgery, radiotherapy and chemotherapy. Treatment is generally provided by a multidisciplinary team which deals with attempts to eradicate cancer and provides support when there are complications of disease and treatment. The team also pays attention to the psychosocial needs of the child and the entire family unit. With recent improvements in cancer therapy, many children are now considered to be "cures." Treatment is tailored to the different subgroups of each disease entity in order to improve response. Research on the etiology of cancer and the treatment of patients with resistant disease is continuously being carried out by cooperative groups. Attention is being directed at the long-term complications occurring in the increasing number of children who have been cured of this still devastating disease. PMID- 1310883 TI - Two biochemical indices of mouse bone formation are increased, in vivo, in response to calcitonin. AB - In a series of four studies, adult female Swiss-Webster mice were used to measure the effects of salmon calcitonin on two biochemical indices of local and systematic bone formation: (1) skeletal alkaline phosphatase activity--in serum and in extracts of calvaria and tibiae, and (2) calvarial collagenase-digestible protein synthesis--measured, acutely, in vitro. Subcutaneous calcitonin doses ranged from 50 to 400 mU/mouse/day (0.95-18.1 U/kg/day), and treatment schedules were continuous (daily) for 2-14 days, acute, or intermittent (2 days/week for 6 weeks). The effects of calcitonin on these bone formation indices (skeletal alkaline phosphatase and collagenase-digestible protein synthesis) were biphasic with respect to dose and treatment time, being increased in response to short term, low-dose treatment, but not long-term, continuous treatment. The effects of long-term intermittent calcitonin treatment were dose-dependent increases in skeletal alkaline phosphatase in calvaria and serum (r = 0.948, P less than 0.02, and r = 0.960, P less than 0.01, respectively). PMID- 1310885 TI - Hemimaxillary odontogenic dysplasia: case report. PMID- 1310886 TI - The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma. AB - Eighteen patients with a biliopancreatic carcinoma in 15 different cancer family syndrome (CFS) families were studied. Only families with three or more first degree relatives with colorectal carcinoma were included, and other characteristics of CFS were required in at least two cases. In 14 patients, the histologic specimen was available for reevaluation. In 11 (79%), the tumor was confirmed as a carcinoma of the biliary tract or papilla of Vater. In three (21%), carcinoma of the pancreas was the most probably alternative. In all four patients without histologic reevaluation, the diagnosis had been carcinoma of the biliary tract. This study suggests that carcinoma of the biliary tract or papilla of Vater is associated more commonly with CFS than with carcinoma of the pancreas. In this respect, CFS resembles familial adenomatosis coli, in which this association previously has been established. PMID- 1310887 TI - Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer. AB - The expression of Ha-ras and fes oncogenes was investigated with the immunohistochemical method in formalin-fixed, paraffin-embedded tissue specimens of 147 lung carcinomas. Positive immunoperoxidase reactions for Ha-ras p21 were found in 80.5% of the adenocarcinomas, 39.5% of the squamous cell carcinomas, 21.4% of the large cell carcinomas, and 15.4% of the small cell carcinomas; those for fes P85 were found in 51.2% of the adenocarcinomas, 26.3% of the squamous cell carcinomas, 35.7% of the large cell carcinomas, and 15.4% of the small cell carcinomas. Both Ha-ras p21 and fes P85 were expressed most frequently and most strongly in adenocarcinoma. In addition, adenocarcinoma showed significantly higher incidence of concomitant expression of Ha-ras p21 and fes P85 as compared with other histologic types of lung cancer. Thus, the authors suggest that the cooperative effects of Ha-ras and fes oncogenes are especially important in the carcinogenesis of adenocarcinoma. In adenocarcinoma, the incidence and grade of Ha-ras p21 expression increased with the degree of histologic differentiation, suggesting that Ha-ras oncogene might be related to cellular differentiation. Papillary adenocarcinoma showed more frequent Ha-ras p21 expression in comparison with acinar adenocarcinoma. In well- or moderately differentiated adenocarcinoma, the incidence and grade of Ha-ras p21 immunoreactivity in the cases with poor prognosis were significantly higher than in those with good prognosis if other major prognostic factors were equivalent in the two groups. The authors propose that the expression of Ha-ras p21 may be one of the useful prognostic factors in such carcinomas. PMID- 1310888 TI - Low incidence of human papillomavirus type 16 DNA in bladder tumor detected by the polymerase chain reaction. AB - Human papillomavirus (HPV) detection was done using the polymerase chain reaction technique on tumor tissue from 44 patients with transitional cell carcinoma of the urinary bladder. Only one of the 44 was associated with HPV infection. The HPV-positive patient was not known to have immunodeficiency or genital warts, and the tumor was not morphologically different from the other tumors. Control experiments excluded the possibility that this finding was caused by contamination of the sample. This study confirms that HPV infection is a rare condition in bladder carcinoma. PMID- 1310889 TI - A phase II randomized study comparing sequential and combined intraarterial cisplatin and radiation therapy in primary brain tumors. A Southwest Oncology Group study. AB - The Southwest Oncology Group conducted a trial of intra-arterial cisplatin (150 mg intravenously every 21 days for 2 doses) administered concomitant with or before radiation therapy. Because of technical difficulties cannulating the artery, 27 of 33 eligible patients were able to receive the cisplatin by arterial injection. Five patients died before completion of the study, and 11 patients in each treatment arm were evaluable for response. Three patients (27%) had an objective tumor regression in each treatment arm. Thromboembolic problems complicated 8 of 57 (14%) chemotherapeutic courses. The median survival for the 33 eligible patients was comparable for both groups: 10.8 months in the concomitant treatment arm and 9.6 months with sequential therapy. Problems related to drug administration and toxicity made it impossible to determine the role of intraarterial cisplatin in the initial management of primary high-grade gliomas. PMID- 1310890 TI - Establishment and characterization of a human T-cell lymphoblastic lymphoma cell line (HT-1) carrying an inversion of chromosome 14. AB - A new human lymphoblastic lymphoma cell line was established (designated HT-1) from the pleural fluid lymphoma cells of a patient with lymphoblastic lymphoma of T-cell type. The HT-1 cells expressed CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD57, and terminal deoxynucleotidyl transferase (TdT) but lacked B-cell-associated antigens and myeloid-associated antigens. In addition, HT-1 cells had rearranged T-cell receptor (TCR) beta-chain gene and gamma-chain gene but retained germlines of immunoglobulin (Ig) heavy chain gene. These findings indicate that HT-1 cell line represents a common thymocyte in the T-cell lineage. Cytogenetic studies revealed that HT-1 cells carry an inversion (inv) of the long arm of chromosome 14. This cell line is the second T-cell line carrying inv(14) chromosome and may be useful for the molecular investigation of the cytogenetic break points of inv(14). PMID- 1310891 TI - Paraneoplastic encephalomyelitis. Dramatic response to chemotherapy alone. AB - Neurologic paraneoplastic syndromes are usually a debilitating and untreatable manifestation of malignancy. The case is presented of a woman with severe paraneoplastic encephalomyelitis that was characterized predominantly by cerebellar degeneration associated with small cell lung cancer, both of which responded rapidly to cytotoxic chemotherapy alone. She is alive with some neurologic residua but no signs of recurrent cancer more than 2 years after diagnosis. Recommendations for aggressive management of this rare but disabling syndrome are outlined. PMID- 1310892 TI - Lack of modulation effects of praziquantel on DMN-induced lesion development in the Syrian hamster liver. AB - The effects of repeated praziquantel administration subsequent to dimethylnitrosamine (DMN) treatment of Syrian hamsters were investigated. The antihelminthic drug was given (200 mg/kg body wt. as a suspension in corn oil, by i.g. intubation) 11 times at 2 week intervals starting at week 4 after initial 20 mg/kg DMN i.p. injections at weeks 0 and 2. Sacrifice at week 28 revealed no differences in either hepatocellular or cholangiocellular lesion development between carcinogen-initiated groups with or without antihelminthic treatment. No lesions were observed in the praziquantel alone or untreated groups. The results thus indicate no promotion potential for praziquantel on nitrosamine-induced lesions in the hamster liver. PMID- 1310893 TI - The cdc25 M-phase inducer: an unconventional protein phosphatase. PMID- 1310894 TI - Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. AB - In man, Hodgkin's disease (HD) represents the most frequent lymphoma entity whose pathogenesis is still unknown. In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2. The open reading frame of the cDNA that can be translated from two mRNA species of 2.6 kb, and 3.8 kb, respectively, predicts a 595 amino acid protein with leader, extracellular, single transmembrane, and intracellular domains. When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen. The CD30 extracellular domain proved to be homologous to members of the nerve growth factor receptor superfamily. Six cysteine-rich motifs could be recognized within the putative ligand-binding domain. PMID- 1310895 TI - The a mating type locus of U. maydis specifies cell signaling components. AB - The a mating type locus of the phytopathogenic fungus U. maydis controls fusion of haploid cells and filamentous growth of the dikaryotic mycelium. The a locus exists in two alleles, termed a1 and a2, which are defined by nonhomologous DNA regions comprising 4.5 kb for a1 and 8 kb for a2, flanked by identical sequences. Based on functional assays, mutants, and sequencing, we demonstrate that the mating type in each allele is determined by a set of two genes. One encodes a precursor for a lipopeptide mating factor, and the other specifies the receptor for the pheromone secreted by cells of opposite mating type. Thus, U. maydis employs a novel strategy to determine its mating type by providing the primary determinants of cell-cell recognition directly from the mating type locus. PMID- 1310896 TI - Functional antagonism between c-Jun and MyoD proteins: a direct physical association. AB - The product of the proto-oncogene Jun inhibits myogenesis. Constitutive expression of Jun in myoblasts interferes with the expression and the function of MyoD protein. In transient transfection assays Jun inhibits transactivation of the MyoD promoter, the muscle creatine kinase enhancer, and a reporter gene linked to MyoD DNA-binding sites. Conversely, MyoD suppresses the transactivation by Jun of genes linked to an AP-1 site. We demonstrate that both in vivo and in vitro MyoD and Jun proteins physically interact. Mutational analysis suggests that this interaction occurs via the leucine zipper domain of Jun and the helix loop-helix region of MyoD. PMID- 1310897 TI - A major palmitoylated membrane protein of human erythrocytes shows homology to yeast guanylate kinase and to the product of a Drosophila tumor suppressor gene. PMID- 1310898 TI - Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. AB - Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder. PMID- 1310899 TI - Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase. AB - A cDNA encoding the TGF-beta type II receptor protein has been isolated by an expression cloning strategy. The cloned cDNA, when transfected into COS cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated TGF-beta 1. Excess TGF-beta 1 competes for binding of radioiodinated TGF-beta 1 in a dose-dependent manner and is more effective than TGF-beta 2. The predicted receptor structure includes a cysteine-rich extracellular domain, a single hydrophobic transmembrane domain, and a predicted cytoplasmic serine/threonine kinase domain. A chimeric protein containing the intracellular domain of the type II receptor and expressed in E. coli can phosphorylate itself on serine and threonine residues in vitro, indicating that the cytoplasmic domain of the type II receptor is a functional kinase. This result implicates serine/threonine phosphorylation as an important mechanism of TGF-beta receptor-mediated signaling. PMID- 1310900 TI - Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. AB - Using positional cloning strategies, we have identified a CTG triplet repeat that undergoes expansion in myotonic dystrophy patients. This sequence is highly variable in the normal population. PCR analysis of the interval containing this repeat indicates that unaffected individuals have been 5 and 27 copies. Myotonic dystrophy patients who are minimally affected have at least 50 repeats, while more severely affected patients have expansion of the repeat containing segment up to several kilobase pairs. The CTG repeat is transcribed and is located in the 3' untranslated region of an mRNA that is expressed in tissues affected by myotonic dystrophy. This mRNA encodes a polypeptide that is a member of the protein kinase family. PMID- 1310901 TI - TNF-alpha differentially regulates Ia antigen expression and macrophage tumoricidal activity in two murine macrophage cell lines. AB - We have assessed tumor necrosis factor-alpha (TNF-alpha) production and its autocrine effects on activation in two murine macrophage cell lines which have distinct responses to the activation stimuli interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS), and compared these responses to those observed in thioglycollate-elicited peritoneal macrophages. IFN-gamma induced TNF alpha production in RAW 264.7 cells and this induction was regulated at the transcriptional level. IFN-gamma did not stimulate TNF-alpha production in either WEHI-3 cells or peritoneal macrophages, although MHC class II antigen expression was induced. LPS stimulated TNF-alpha production in the RAW 264.7 cell line and peritoneal macrophages; however, no TNF-alpha was detected in WEHI-3 cells activated with LPS. We also assessed the ability of endogenous TNF-alpha to serve as an autocrine regulator of two aspects of IFN-gamma-mediated macrophage activation, namely, induction of antibody-independent tumoricidal activity and induction of MHC class II antigen expression. These studies revealed that TNF alpha could act synergistically or antagonistically with IFN-gamma in the regulation of these two functions, depending on both the macrophage population used and the function assessed. The results of our experiments suggest that the mechanism of induction of TNF-alpha production by IFN-gamma or LPS, and the ultimate autocrine contribution of such TNF-alpha to a given activation response, is dependent on the activated macrophage target population under analysis. The WEHI-3 and RAW 264.7 cell lines provide a model system for comparative exploration of the mechanistic basis of this differential regulation. PMID- 1310902 TI - Cholera toxin promotes the proliferation of anti-mu antibody-prestimulated human B cells. AB - The predominant effect of cholera toxin (CT) on cell growth has been postulated to be inhibitory as a result of its induction of intracellular cAMP. We have recently reported that CT selectively enhances surface DR expression while it inhibits anti-mu antibody-induced B lymphocyte proliferation. In the present series of experiments we studied the effect of CT on in vitro preactivated highly purified (greater than 95% CD20+) human B cells. Cholera toxin enhanced thymidine incorporation of anti-mu antibody-preactivated but not of Staphylococcus aureus Cowan I or PMA + ionomycin-preactivated B cells. Concentrations of 100 pg/ml CT stimulated an enhancement of thymidine incorporation equivalent to that of optimal doses of BCGF. The growth factor-like effect of CT required the complete molecule, since binding of purified B subunit (B-CT) to GM1 ganglioside by itself did not reproduce the holotoxin effect. Moreover, B-CT pretreatment of anti-mu antibody-primed cells completely neutralized the holotoxin-enhancing effect. Both PGE2, a physiological agent that stimulates intracellular cAMP elevation, and the cAMP analogue, 8-bromo-cAMP, mimicked the growth-promoting effect of CT. However, the ED50 of CT required to augment proliferation in anti-mu antibody-preactivated human B cells was approximately 100 times less than the ED50 for cAMP formation. These results demonstrate a specific growth factor-like promoting effect of CT on sIg-preactivated highly purified human B cells that may be mediated at least in part through elevation in intracellular cAMP levels. Increased DR expression and stimulation of growth of sIg preactivated B cells may explain some of the adjuvant properties of CT following orally or parenterally administered antigens. PMID- 1310903 TI - The effect of a shift from a mixed diet to a lacto-vegetarian diet on human urinary and fecal mutagenic activity. AB - This is an investigation of the effects of a shift from a well-balanced mixed diet to a lacto-vegetarian diet on the mutagenic activity in urine and feces. The participants were 20 normal-weight, non-smoking subjects (4 men and 16 women, mean age 44 years, range 27-61 years). The fecal samples were assayed for direct acting mutagens with the fluctuation test for weak mutagens and the urinary samples were assayed with the same assay but with a metabolic activation system, a so-called S9 fraction. The switch from a mixed diet to a lacto-vegetarian diet was not a shift from a so-called high to a low risk diet for colon cancer but rather from a 'medium high risk diet' to a 'low risk diet', even though there were significant changes in nutrients and food components between the two diets. There was a decrease in fat (P = 0.009) and protein intake (P = 0.04) and an increase in total carbohydrate (P = 0.001), fiber (P = 0.001), calcium (P = 0.006) and vitamin C intake (P = 0.019). Among the food preparation methods the use of frying decreased (P = 0.02) and the habit of eating a new vegetable meal increased (P = 0.05). Three months after the dietary shift the concentration of fecal direct-acting mutagens decreased significantly (P less than 0.05), though the total mutagenic activity excreted in feces per 24 h was not different between the two diet periods. Both the concentration and the total amount of promutagens in the urine were decreased after 3 months on the lacto-vegetarian diet. The decrease in fecal mutagenic activity might be explained by a higher fiber intake, which leads to higher water content in feces and thereby a dilution of fecal mutagenic compounds. PMID- 1310904 TI - Regulation of gap junctional communication in Syrian hamster embryo cells by retinoic acid and 12-O-tetradecanoylphorbol-13-acetate. AB - Retinoids enhance the frequency of Syrian hamster embryo (SHE) cell colonies with transformed morphology in a similar way to tumor-promoting phorbol esters. The present study shows that retinoids are also potent inhibitors of gap junctional intercellular communication in SHE cells at noncytotoxic concentrations. This is an apparent contrast to the results observed in transformation systems using the mouse cell lines C3H10T1/2 and BALB/c 3T3, where retinoids have been found to reduce the induction of transformation, and also to enhance gap junctional cell communication. Retinoids are thus potent modulators of transformation and cell communication in three transformation systems. For all three cell types, enhancement of communication by retinoids is related to reduced transformation, and inhibition of communication to enhanced induction of transformation. Communication in the SHE cells is completely blocked following 1 h exposure to 30 microM retinoic acid, while concentrations of 0.3-15 microM results in a gradual down-regulation of communication during 1-5 h exposure. Removal of retinoic acid results in complete restoration of communication to control values within a few hours. Primary SHE cells and the cell line BPNi show similar sensitivity for inhibition of communication after exposure to retinoic acid, while BPNi cells are far more sensitive to inhibition of communication by 12-O-tetradecanoylphorbol-13 acetate (TPA) than primary SHE cells. Retinoic acid does not induce inhibition of epidermal growth factor binding, potentiate adenylate cyclase activation or enhance arachidonic acid release, as does TPA, suggesting different mechanisms of action. PMID- 1310905 TI - Spin-labeled phorbol esters and their interactions with cellular membranes--IV. Lipophilic binding and molecular orientation of spin-labeled phorbol-12,13 diesters in human erythrocyte membrane. AB - In human erythrocyte membranes, membrane binding of spin-labeled TPA-analogous phorbol (doxyl)esters [(n,m)PA] was investigated during measurement of the kinetics of the decay of their electron paramagnetic resonance signal by ascorbate reduction. In membrane-bound (n,m)PA the reduction rate was dependent of the position of doxyl in the aliphatic chain of their 12-O-acyl moiety. To describe quantitatively the reaction kinetics observed, two hypotheses (models) were developed and used. Model 1 is based on the assumption that ascorbate reduction takes place in the extracellular space. In this case the experimental data could be fitted by the partition and permeability coefficients of (n,m)PA determining model 1 only, if non-realistic values of these parameters were used. The more refined model 2, corresponding to a bilayer membrane structure, assumes the reduction to take place in the hydrophilic region of the membrane. Assuming a finite probability of finding the doxyl group within the hydrophilic membrane region, model 2 describes quantitatively the dependence of the reduction rate on the position of the doxyl in the aliphatic chain of the (n,m)PA used. From the validity of this model it may be postulated that the molecular orientation of TPA analogous (n,m)PA in the bilayer membrane is determined by an anchoring of their lipophilic ester moiety in the lipophilic region of the membrane bilayer, thus locating the hydrophilic phorbol moiety within the hydrophilic region of the membrane. With regard to the well-known categories of non-specific versus specific binding of bioactive phorbol esters to protein kinase C/membrane complexes it is deduced that anchoring of (n,m)PA (and hence TPA) in the hydrophobic interior of the membrane structure may be the molecular equivalent of their non-specific binding. PMID- 1310906 TI - Spin-labeled phorbol esters and their interactions with cellular membranes--V. Electron paramagnetic resonance of spin-labeled phorbol-12,13-diesters bound to their receptors in mouse brain particulate fraction. AB - The relatively small concentrations required for in vivo bioactivity of diterpene ester skin irritants and promoters (approximately 10 nmol per animal; approximately 10 nM in cell cultures) has discouraged studies of EPR spectra of bioactive, TPA-analogous, spin-labeled phorbol-12,13-diesters [(n,m)PA] bound to their membrane receptors, protein kinases C (PKC). To meet the requirements of present EPR spectrometers, particulate fraction from mouse brain containing at least 25 x 10(-12) mol of receptors/mg protein (PKC species) were employed together with certain (n,m)PA selected to give an optimal ratio of specific to non-specific binding. For selection and optimization of experimental conditions, a theoretical model was developed that considers all characteristic parameters of the system. By fitting the model calculations to the experimental data of competitive agonist displacement from the particulate fraction of tritium-labeled TPA, the dissociation constants Kd for four selected (n,m)PA used as antagonists were determined. Optimal experimental conditions are met by (5,6)PA and by (5,8)PA, in that for both compounds the relative amount of displaced (n,m)PA is in accordance with the predictions derived from the model. Moreover, the model turned out also to be reliable for samples containing either small or large amounts of membranes. To obtain an EPR spectrum of an agonist bound to brain particulate fraction, the (5,6)PA was used. It shows a broad EPR spectrum typical for an immobilized molecule. The spectrum changes if an excess of TPA is added to the system; the slight differences in shape are due to displacement of (5,6)PA from specific receptor sites by non-labeled TPA and show up as a decreased central peak amplitude. This is the first time that the agonist/receptor interaction of a diterpene ester type irritant and tumor promoter has been demonstrated by direct spectroscopic measurement. PMID- 1310907 TI - Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethionine-supplemented diet. AB - Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine (CDE) for 4, 6, 10, 14 or 22 weeks followed by a standard diet for up to 59 weeks. Liver sections were histochemically analyzed for the following parameters: basophilia, glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The stop experiments revealed that many of the oval cells proliferating during the first 4-6 weeks may undergo necrotic changes and disappear with time, whereas cholangiofibroses appearing in animals fed CDE for at least 10 weeks are persistent lesions. The sequence of lesions seen in this study, leading from persistent oval cells through cholangiofibroses to cholangiofibromas, strongly suggests that the oval cells are the precursor cells of cholangiocellular tumors. The proliferating oval cells and the hepatic foci consisting of clear and acidophilic or mixed cell populations were always spatially separated and no transitions between oval and parenchymal cells were observed. These results argue against a precursor-product relationship between oval and parenchymal cells. Both proliferating and persistent oval cells, cholangiofibroses and cholangiofibromas showed a strong staining for G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT; low PHO, SYN and G6PASE activities were also detected in these lesions. Persistent glycogen-storage foci, which developed in all rats fed CDE for 4-14 weeks followed by a normal lab chow for over a year, had increased PHO, G6PDH, MDH, ALKPASE and GGT activities, while SYN, GAPDH and G3PDH activities remained unaltered and G6PASE activity decreased. Mixed cell foci appearing in animals fed CDE for 22 weeks followed by a normal lab chow for 59 weeks had strongly increased G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities as well as decreased G6PASE activity. These results indicate that the characteristic metabolic pattern of preneoplastic hepatic foci is independent of the further administration of the carcinogenic diet. The shift from glycogen metabolism to glycolysis and the pentose phosphate pathway occurring during the later stages of CDE-induced hepatocarcinogenesis is an autogenous process apparently directing the disturbed carbohydrate metabolism towards alternative metabolic pathways. A similar metabolic shift also seems to take place during cholangiocarcinogenesis. PMID- 1310908 TI - Insulin resistance, adipose tissue and coronary heart disease. PMID- 1310909 TI - Insulin resistance and Na+/K(+)-ATPase in hypertensive women: a difference in mechanism depending on the level of glucose tolerance. AB - 1. The peripheral glucose disposal rate (assessed with the euglycaemic hyperinsulinaemic clamp technique), the serum sex hormone-binding globulin concentration and total and ouabain-sensitive 22Na-efflux rate constants in leucocytes were determined in 41 women with impaired glucose tolerance and in 40 women with normal glucose tolerance. The groups were matched for body mass index and diastolic blood pressure (range 55-112 mmHg). 2. Stepwise regression analysis showed that diastolic blood pressure in the group with impaired glucose tolerance was inversely correlated with the glucose disposal rate (model r2 = 21%) and was correlated with the plasma glucose concentration at 120 min after an oral glucose load (model r2 = 31%). In the group with normal glucose tolerance, however, neither of these two variables was correlated with blood pressure, although the ouabain-sensitive 22Na efflux rate constant was (model r2 = 11%). 3. Among insulin-resistant subjects, those with hypertension had significantly lower serum sex hormone-binding globulin concentrations than the normotensive subjects. 4. We conclude that insulin resistance is correlated with high blood pressure in women with glucose intolerance and increased androgenic activity. In women with normal insulin sensitivity, a low level of the Na+/K(+)-ATPase-mediated sodium efflux is associated with high blood pressure. PMID- 1310910 TI - Plasma and platelet free catecholamine concentrations in patients with familial hypercholesterolaemia. AB - 1. Plasma and platelet free catecholamine concentrations were measured in 22 normal subjects and in 10 treated and 11 untreated patients with heterozygous familial hypercholesterolaemia. 2. Plasma noradrenaline concentrations were significantly higher in both treated and untreated hypercholesterolaemic patients than in normal subjects. Adrenaline concentrations did not differ. 3. Platelet noradrenaline levels were higher in untreated hypercholesterolaemic patients than in normal subjects. 4. Positive correlations between the plasma noradrenaline concentration and the platelet noradrenaline concentration were observed in both normal subjects and hypercholesterolaemic patients. 5. Combining the data for normal subjects and hypercholesterolaemic patients revealed that the plasma noradrenaline concentration correlated positively with the plasma cholesterol concentration. The platelet noradrenaline concentration was also found to correlate with the plasma cholesterol concentration. 6. Our results suggest that an increased plasma cholesterol concentration may be associated with increased sympathetic nervous system activity as indicated by elevated plasma and platelet noradrenaline levels. Increases in circulating catecholamines may contribute to the platelet hyperaggregability seen in familial hypercholesterolaemia. PMID- 1310911 TI - Difficulties in measuring oxidized glutathione in biological samples. PMID- 1310912 TI - Renal filtration, reabsorption and excretion of aluminium in the rat. AB - 1. Plasma and urinary aluminium levels, and renal function, were investigated in a control group of rats (n = 5) and in two groups that received an intravenous bolus dose of aluminium chloride (either 25 micrograms or 800 micrograms of aluminium, n = 7 and 5, respectively). 2. In the control group (plasma aluminium concentration 76.8 +/- 14.2 ng/ml), 59.4 +/- 3.5% of the plasma aluminium was ultrafilterable. The percentage ultrafilterable after the administration of 25 micrograms of aluminium was 41.9 +/- 7.8 (plasma concentration 154.3 +/- 18.6 ng/ml). However, after administration of 800 micrograms of aluminium, to give a plasma concentration of 19,800 +/- 2956 ng/ml, only 1.06 +/- 0.13% was ultrafilterable. 3. Such results have generally been interpreted as indicating an increase in protein-binding of aluminium with increasing aluminium concentration. In buffered aqueous solutions of aluminium chloride at pH 7.4, with an aluminium concentration of 189 +/- 6 ng/ml, 96.12 +/- 0.02% was ultrafilterable (n = 6). This concentration is comparable with that attained in the low-dose (25 micrograms) aluminium group of animals and suggests that the difference between the ultrafilterable percentage of aluminium in plasma compared with that in aqueous solution is indeed due to the binding of aluminium to high Mr material (proteins). In contrast, however, in an aqueous buffered (pH 7.4) solution containing 28,200 ng of aluminium/ml, only 1.05 +/- 0.09% was ultrafilterable. This indicates insolubility (i.e. colloid formation) of the aluminium at this high concentration. The same percentage (1.06 +/- 0.13) was ultrafilterable from plasma from the high-dose (800 micrograms) aluminium group with a plasma aluminium concentration of 19,800 +/- 2956 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310913 TI - Persistent albuminuria in normotensive non-insulin-dependent (type II) diabetic patients: comparative effects of angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers. AB - 1. Some non-insulin-dependent (type II) diabetic patients show albuminuria without arterial hypertension. In these patients, angiotensin-converting enzyme inhibitors reduce urinary albumin excretion without producing any changes in systemic blood pressure and renal haemodynamics. However, up to now it has not been clear whether these favourable renal effects are specifically related to angiotensin-converting enzyme inhibition or not. 2. Twelve type II diabetic outpatients with persistent macroalbuminuria (greater than 300 mg/daily on at least three consecutive occasions), without any other signs of renal disease and whose blood pressure was persistently below 140/90 mmHg, were studied. 3. In a randomized sequence and in a double-blind fashion, after a 2-month run-in period, patients were allocated to receive 5 mg of enalapril or 50 mg of atenolol daily for the next 6 months. At the end of this first period and after 6 months on placebo in a cross-over fashion, active treatment was replicated. Blood pressure and urinary albumin excretion were measured every 2 months, whereas the other variables studied were determined at the end of each period. 4. Kidney function and blood pressure did not change significantly, whereas albuminuria decreased significantly, after both of the drugs. 5. These data suggest that the inhibition of tissue angiotensin formation and the consequent reduction in glomerular permeability, rather than changes in renal and systemic haemodynamics, are the common mechanisms by which both enalapril and atenolol decreased albuminuria in our patients. PMID- 1310914 TI - Model-based determination of cut-off values for left ventricular hypertrophy from echocardiographic myocardial mass data. AB - 1. The left ventricular myocardial mass is a measurement that is easy to obtain by echocardiography. It is currently used for the definition of left ventricular hypertrophy, but cut-off values are often critical, since they depend on covariates of left ventricular myocardial mass such as sex, age, body surface area, physical training, blood pressure, etc. As it is very difficult in any laboratory to obtain a sufficient number of normal subjects for the establishment of left ventricular myocardial mass experimental distributions, we propose a non linear model for the calculation of echocardiographic left ventricular myocardial mass distribution in normal subjects, from personal and literature data. left ventricular myocardial mass probability density function was computed from the following two assumptions: the joint distribution of the internal and external left ventricular diameters is assumed to be bivariate normal, and the relation between left ventricular myocardial mass and ventricular diameters is given by the formula of Devereux & Reicheck (Devereux, R. B. & Reicheck, N. Circulation 1977; 55, 613-8). 2. The Gaussian assumption was tested by using skewness tests. The model was further developed for the myocardial mass index distribution. The calculated probability density functions were compared with experimental data and showed very good agreement. Furthermore, they were used to define cut-off values of left ventricular hypertrophy at selected false-positive ratios. Finally, since left ventricular myocardial mass may vary under normal conditions with co variates, the model may provide co-variate-matched cut-off values for any, even small, series of non-diseased control subjects. PMID- 1310915 TI - Effect of induced supraventricular tachycardias on changes in urine output and plasma hormone levels in man. AB - 1. A symptomatic diuresis, polyuria, sometimes accompanies paroxysmal tachycardias in man. A study was undertaken in patients with inducible supraventricular tachycardia, irrespective of the symptom of polyuria, to measure simultaneous changes in urine output and plasma hormone levels during the arrhythmia. 2. During 14 episodes of induced tachycardia in 10 patients, there was a significant increase in mean urine flow, which was independent of the state of patient hydration. During a mean tachycardia duration of 30 +/- 3 min, the mean group urine flow increased from 3.2 +/- 2.3 ml/min to 7.6 +/- 3.7 ml/min (P less than 0.001). This was characterized by a consistent increase in free water excretion and a variable increase in sodium excretion. 3. The plasma atrial natriuretic peptide level (five patients) significantly increased from 7.6 +/- 4.6 pg/ml to 34.6 +/- 21.7 pg/ml (P less than 0.02) during the arrhythmia. There was no significant change in the plasma arginine-vasopressin level and a non significant reduction in plasma renin activity. 4. This study has shown that induced supraventricular tachycardias in man are accompanied by a significant diuresis. The mechanisms responsible remain unknown, but do not appear to involve the plasma arginine-vasopressin level alone. PMID- 1310916 TI - Electrocardiographic changes during steady mild hypothermia and normothermia in patients with poikilothermia. AB - 1. ECG changes observed in short-term induced and accidental hypothermia are well known. To assess the influence of steady-state spontaneous hypothermia on the ECG, we subjected four patients with acquired poikilothermia (severe thermolability) to 24 h ECG recording, exercise testing and thermal stress. 2. Twenty-four hour Holter monitoring showed a significant reduction in heart rate and a prolongation of the QT interval during steady-state mild hypothermia (rectal temperature 33.9 +/- 0.7 degrees C, mean +/- SD) compared with during normothermia; no significant changes occurred in the PR interval, QRS complex and QTc interval (QT interval corrected for heart rate). 3. Unlike during normothermia, during steady hypothermia atrioventricular Wenckebach blocks were observed in two patients, whereas another patient showed markedly more atrioventricular Wenckebach blocks during hypothermia. 4. During steady hypothermia the heart rate variability was significantly enhanced in comparison with normothermia. 5. Exercise tolerance was similar during mild hypothermia and normothermia. 6. Heat exposure (ambient temperature 40 degrees C) induced significantly greater changes in rectal temperature, heart rate and PR interval, QRS complex and QT interval in the patients than in the control subjects (n = 8). 7. The present study reveals that even mild steady spontaneous hypothermia can elicit ECG changes, presumably mediated by relatively enhanced cardiac vagal tone. Hence, spontaneous abnormalities in core temperature should be taken into account in interpreting the ECG in clinical practice. PMID- 1310917 TI - Nocturnal variations in lower-leg subcutaneous blood flow in paraplegic men. AB - 1. Lower-leg subcutaneous adipose tissue blood flow rates were measured over 12 20 h under ambulatory conditions by means of the 133Xe-washout technique in nine paraplegic men, all with complete spinal cord lesions at or below the Th 6 level, and in nine age-matched healthy men. Portable CdTe(Cl) detectors and data-storage units were used. 2. The central and local sympathetic vasoconstrictive activity at the lower leg was measured under laboratory conditions by means of the 133Xe washout technique and a stationary NaI(Tl) detector system. 3. The paraplegic men were found to have intact central and local sympathetic vasoconstrictive activity in their lower legs. Moreover, they all had a nocturnal hyperaemic blood flow phase of the same magnitude and duration as the control subjects. 4. The possibility that the somaesthetic nerves play a role in the hyperaemic response could be excluded, as all the paraplegic men suffered from complete lower-leg somaesthetic denervation. 5. A significant correlation was found between the time of going to bed and the nightly hyperaemic response in the right and left lower legs (P less than 0.01). 6. It is concluded that the present data are in accordance with the concept of a central nervous or humoral elicitation of nocturnal hyperaemia, although local metabolic and other factors might participate as well. Paraplegic men have an intact regulation of the postural and nocturnal changes in peripheral blood flow whether of central sympathetic or humoral origin. PMID- 1310918 TI - A comparison of the pharmacological and mechanical properties in vitro of large and small pulmonary arteries of the rat. AB - 1. The mechanical and pharmacological properties of small pulmonary arteries (100 300 microns normalized lumen diameter) were directly compared with those of the left main pulmonary artery (1-2 mm) from the rat. The active and passive length tension characteristics and responses to a variety of agonists and antagonists were dependent on arterial diameter. 2. Maximum contractile function was obtained in both groups of vessels when stretched so as to give an equivalent transmural pressure of 30 mmHg. This is substantially lower than that found for systemic vessels, and reflects the normal low pulmonary arterial pressure. 3. Noradrenaline was a powerful vasoconstrictor in large but not small pulmonary arteries (P less than 0.001). In contrast, bradykinin produced a significantly greater response in the small arteries (P less than 0.001). In comparison with large pulmonary arteries, small arteries were more sensitive to noradrenaline (P less than 0.05) and 5-hydroxytryptamine (P less than 0.001), less sensitive to endothelin-1 (P less than 0.001) and had the same sensitivity to prostaglandin F2 alpha. 4. The mechanism that maintains the low arterial tone of the pulmonary circulation is unknown, but it may involve the release of relaxing factors from the endothelium. In this preparation, basal resting tone could not be demonstrated in either large or small arteries. 5. Acetylcholine-induced relaxation of pre-contracted pulmonary arteries was reduced or absent in the small artery, despite histological evidence of an intact endothelium. In large arteries pre-contracted with prostaglandin F2 alpha, acetylcholine (100 mumol/l) caused 88.2% relaxation compared with 25.2% in the small artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310919 TI - Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose. AB - 1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg 1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310920 TI - Increased energy expenditure in cystic fibrosis is associated with specific mutations. AB - 1. Measurements of resting metabolic rate were made by open-circuit indirect calorimetry in 78 unrelated cystic fibrosis patients and 30 healthy control subjects. The aims of this study were: (i) to determine the range of variability in resting metabolic rate in cystic fibrosis, (ii) to relate this to pulmonary function and body size, and (iii) to investigate the hypothesis that, in cystic fibrosis, genotype exerts a significant influence on energy requirements. 2. There was no significant difference in age or body weight between patients with cystic fibrosis and control subjects. Resting metabolic rates for control subjects fell within +/- 10% of predicted values. Fifty-nine per cent of patients with cystic fibrosis had elevated resting metabolic rates (i.e. greater than 111% of predicted). Genotype analysis divided the patients with cystic fibrosis into three groups: delta F508 homozygotes, delta F508 heterozygotes and others. Patients homozygous for the delta F508 allele had a significantly higher resting metabolic rate (121% of predicted, 95% confidence interval 116-126%), compared with other genotypes (P less than 0.005). 3. There were significant differences in pulmonary function between the groups (P less than 0.005). However, after adjustment of individual resting metabolic rates for differences in pulmonary function by using analysis of covariance, resting metabolic rates remained significantly higher for delta F508 homozygotes than for other genotypes (P less than 0.05). 4. We conclude that there is a significant contribution to resting metabolic rate in cystic fibrosis associated with specific mutations that is not explained by declining pulmonary function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310921 TI - Metabolic effects of dobutamine in normal man. AB - 1. Dobutamine in 5% (w/v) D-glucose was infused at sequential doses of 2, 5 and 10 micrograms min-1 kg-1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) D-glucose alone. 2. The energy expenditure increased and was 33% higher than control (P less than 0.001) at 10 micrograms of dobutamine min-1 kg-1. The respiratory exchange ratio decreased from 0.85 (SEM 0.02) before infusion to 0.80 (SEM 0.01) at 10 micrograms of dobutamine min-1 kg 1, but did not alter during the placebo infusion (P less than 0.001). 3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of D-glucose alone (P less than 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions. 4. Compared with during the placebo infusion, the blood glucose concentration decreased (P less than 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P less than 0.001), and the plasma potassium concentration decreased from 3.8 (SEM 0.07) to 3.6 (SEM 0.04) mmol/l (P less than 0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 micrograms of dobutamine min-1 kg-1 (P less than 0.001) with no further rise at 10 micrograms of dobutamine min-1 kg-1. 5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310923 TI - Damage to erythrocytes from long-term heat stress. AB - 1. Erythrocytes are known to haemolyse in vitro at 48-50 degrees C. We hypothesized that erythrocytes might be damaged at much lower temperatures if they are incubated for prolonged periods. Erythrocytes from healthy human donors (n = 7) were incubated at 37, 40, 42, 44, 46 or 48 degrees C for 4-48 h. The haemolytic percentage and osmotic fragility were then measured by a modification of the method of Parpart et al. 2. Significant haemolysis and increased fragility were not observed at any temperatures after incubation for 4 h. However, the haemolytic percentage increased after incubation for 24 h at 44 degrees C (9.1 +/ 4.9%, P less than 0.01), 46 degrees C (52.4 +/- 14.1%, P less than 0.01) and 48 degrees C (98.0 +/- 2.6%, P less than 0.01) and after incubation for 48 h at 42 degrees C (9.8 +/- 4.5%, P less than 0.01) when compared with the values before heating (1.1 +/- 0.9%). The osmotic fragility also increased after incubation for 24 h at and above 42 degrees C. 3. Although heat-induced haemolysis and an increase in fragility have not been known to occur below 48 degrees C, these were quite apparent after incubation for 24-48 h at only 42 degrees C. This suggests that with regard to thermal effects, it is important to consider not only the temperature but also the duration of heating. PMID- 1310922 TI - Effects of chronic administration of ephedrine during very-low-calorie diets on energy expenditure, protein metabolism and hormone levels in obese subjects. AB - 1. We investigated the effects of the chronic administration of a sympathomimetic agent on energy expenditure, protein metabolism and levels of thyroid hormones and catecholamines in 10 obese subjects after a 6-week very-low-calorie-diet programme (1965 kJ, 60 g of protein, 45 g of carbohydrates). L-(-)-Ephedrine hydrochloride (50 mg three times a day by mouth) or placebo were administered during 2-week periods (weeks 2-5 of the VLCD programme) in a randomized, double blind, cross-over design. Five subjects began with ephedrine and five with placebo. 2. The results were analysed separately in the two groups. No difference was found between them as regards weight loss during the very-low-calorie diet and drug treatments. Conversely, ephedrine therapy induced a significantly lower daily urinary excretion of nitrogen (and, consequently, a better nitrogen balance) with respect to placebo, independently of the drug sequence. Daily urinary levels of 3-methylhistidine during ephedrine and placebo treatments were similar. The fasting resting metabolic rate (oxygen consumption, ml STP/min) fell significantly during the very-low-calorie diet in both groups, but this effect was partially and significantly prevented by administration of ephedrine. Diet therapy significantly reduced 24 h urine levels of vanillylmandelic acid and homovanillic acid, which, however, increased to pretreatment values during ephedrine treatment. No significant effects were shown on 24 h urinary concentrations of adrenaline, noradrenaline and dopamine during the very-low calorie diet and/or ephedrine treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1310924 TI - Correlation of the ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine in the brain and cerebrospinal fluid of the pig: implications for the determination of this methylation ratio in human brain. AB - 1. Pigs were maintained in air or in an atmosphere of nitrous oxide which dramatically changes the S-adenosyl-L-methionine to S-adenosyl-L-homocysteine ratio in neural tissues. Samples of cerebrospinal fluid, cortex, cerebellum and spinal cord were then extracted and analysed for S-adenosyl-L-methionine and S adenosyl-L-homocysteine. Regression analyses were carried out on values obtained in cerebrospinal fluid and in neural tissues. 2. Highly significant correlations were obtained between levels of S-adenosyl-L-homocysteine (r2 = 0.42-0.69; P less than 0.001) and S-adenosyl-L-methionine/S-adenosyl-L-homocysteine ratios (r2 = 0.56-0.65; P less than 0.001) in cerebrospinal fluid and levels and ratios in cortex, cerebellum and spinal cord. The levels of S-adenosyl-L-methionine did not show a significant correlation. 3. We conclude that the ratio of these metabolites in the cerebrospinal fluid may reflect the ratio in the central nervous system and we suggest that this may also be true in human tissues. This finding will permit the determination of the probable methylation ratio in the central nervous system in human conditions, such as vitamin B12 deficiency and acquired immune deficiency syndrome, where a similar myelopathy occurs to that seen in the nitrous oxide-treated pig. All three myelopathies may arise from an inhibition of methyltransferases involved in the synthesis of myelin that would occur when the methylation ratio is reduced. PMID- 1310925 TI - Membrane incorporation of non-esterified fatty acids and effects on the sodium pump of human erythrocytes. AB - 1. Sodium pump function has been assessed by measurement of ouabain-sensitive 86Rb uptake in human erythrocytes after incorporation of palmitic, stearic, oleic and linoleic acids into the erythrocyte membrane. 14C-labelled fatty acids were used to measure membrane uptake of these substances. 2. For palmitic, oleic and linoleic acids, up to 1000 nmol of the fatty acid/ml of packed cells can be incorporated without causing significant haemolysis. For stearic acid, 270 nmol/ml of packed cells was incorporated in similar conditions. More than 88% of the fatty acid incorporated could be extracted with a 50 mumol/l fatty-acid-free albumin solution and was, therefore, in a non-esterified form in the erythrocyte membrane. The concentrations of palmitic, stearic, oleic and linoleic acids incorporated in these experiments represent a five- to ten-fold increase above the normal concentrations of these fatty acids in the membrane. 3. Up to 1000 nmol of palmitic, oleic and linoleic acids/ml of packed cells and up to 270 nmol of stearic acid/ml of packed cells could be incorporated without a significant change in mean ouabain-sensitive 86Rb uptake with respect to control cells. Mean percentage changes in ouabain-sensitive 86Rb uptake for all these experiments were: palmitic acid, 3.7% (SD 11.4, n = 15); stearic acid, 4.0% (SD 5.7, n = 7); oleic acid, -4.8% (SD 19, n = 17); linoleic acid, 2.2% (SD 15.6, n = 19). 4. The demonstration of near-normal sodium pump activity in the presence of greatly elevated membrane levels of these fatty acids makes it extremely unlikely that they act as modulators of sodium pump function in vivo. PMID- 1310926 TI - Direct immunofluorescence testing for immunoglobulin deposits in haired skin, nasal planum and footpads of woodchuck hepatitis virus-infected woodchucks with chronic hepatitis and multiple hepatocellular carcinomas. AB - The purpose of this study was to determine the frequency of immunoglobulin deposition in the haired skin, footpads, and nasal planums of 10 WHV-infected woodchucks with chronic hepatitis and hepatocellular carcinoma and compare these results with those reported in humans. Immunoglobulin deposition was detected in the skin samples of 3 of 10 woodchucks. Granular deposits were revealed in the superficial dermal blood vessels of the nasal planum, lateral thoracic skin, and footpads in 1 animal each. In 1 of these animals, (lateral thorax) immunoglobulin deposition was concurrently present at the basement membrane zone. PMID- 1310927 TI - Identification of the site of severe colon bleeding by technetium-labeled red cell scan. AB - In cases of severe colon bleeding, it is more important to know the site than the cause, in case surgery is required. Technetium-labeled red-cell scan (TLRCS) is known to identify the site of bleeding at the rate of 0.1 ml per minute or more. The aim of this retrospective study was to see whether TLRCS was a reliable indicator of the site of severe colon bleeding. A retrospective study was made of patients investigated in this way for acute, severe colon bleeding at St. Vincent's Hospital, Melbourne, from 1984 to 1988 (five years). TLRCS identified the site of bleeding in less than half of the cases but correctly identified the site in all nine patients in whom bleeding was so severe as to require emergency surgery, avoiding total colectomy in eight cases. PMID- 1310928 TI - Adenocarcinoma of an ileostomy in a patient with familial adenomatous polyposis. Report of a case. AB - A case of adenocarcinoma arising in an ileostomy of 39 years' duration is presented. The patient had undergone proctocolectomy in 1949 for familial adenomatous polyposis, with subsequent ileostomy in 1950, and presented in April 1989 with bleeding and a mass at the stoma site. Biopsy of the mass revealed adenocarcinoma. Adenocarcinoma of an ileostomy is a rare but well-documented complication, with the present patient bringing the total number of reported cases to 18. The literature is reviewed, and surveillance measures are suggested. PMID- 1310929 TI - Expression of prepro-enkephalin in human articular chondrocytes is linked to cell proliferation. AB - This study shows that cultured human articular chondrocytes express high levels of 1.4 kb prepro-enkephalin mRNA. Chondrocytes store met-enkephalin intracellularly and secrete this neuropeptide in mature as well as in precursor form. Gene expression is inducible by serum factors. High levels of prepro enkephalin mRNA are detected in proliferating chondrocytes but not in confluent, contact-inhibited cells. Phorbol myristate acetate and dibutyryl cyclic AMP, but not dexamethasone, increase levels of prepro-enkephalin mRNA. Furthermore, transforming growth factor beta (TGF beta) and platelet derived growth factor (PDGF) upregulate gene expression, whereas retinoic acid, which inhibits chondrocyte proliferation, suppresses both basal and induced gene expression. Using in situ hybridization it is shown that only 1-3% of primary chondrocytes express prepro-enkephalin mRNA, whereas 52 +/- 12% of subcultured cells are strongly positive. Analysis of DNA synthesis, by autoradiography of incorporated [3H]thymidine, shows that these numbers correspond to the percentage of cells in S-phase of the cell cycle. In cultures of primary chondrocytes TGF beta promotes the formation of cartilage nodules and stimulates proliferation of adherent cells. This is associated with high levels of prepro-enkephalin mRNA in proliferating cells but not in contact-inhibited cells in cartilage nodules. In contrast, formation of cartilage nodules, proliferation and the expression of enkephalin are suppressed by interleukin-1 beta. In summary, expression of prepro enkephalin in human articular chondrocytes is differentially controlled by cartilage regulatory factors and closely associated with cell proliferation. PMID- 1310931 TI - Cell specificity of transcription regulation by papovavirus T antigens and DNA replication. AB - Simian virus 40 (SV40) and polyomavirus (Py) DNA replication require cellular proteins and a virus-encoded early gene product, large T antigen (SVT and PyT, respectively). Primate cells contain factors permissive for SV40 replication, whereas murine cells express those factors permissive for Py. We have compared the roles T antigen, cell permissiveness and replication play in transcription of SV40 and Py genes. We show that in their respectively permissive cells, SV40 replication causes a major shift in transcription initiation from the early to the late viral promoter, whereas when Py replicates a comparable shift does not occur. This difference is discussed in relation to differences in the organization of the origin and promoter region between these two papovaviruses. Reporter plasmids were constructed that carried both viral origins, one at the natural position in the promoter being tested and the other at a distal location. With the appropriate TAg, these vectors could be made to replicate in either primate (HeLa) or rodent (3T6) cells. The SV40 early to late shift occurred when replication was driven in HeLa cells, and was not seen on replicating templates in rodent cells. Thus, replication per se does not account for the shift. We show also that, like SVT, PyT is a potent activator of transcription, and that SVT and PyT can activate each other's late promoters independently of DNA replication, but only in cells permissive for DNA replication catalysed by the respective T antigen. Taken together, the data presented here suggest that papovaviruses may utilize permissive factors in transcription control mechanisms. PMID- 1310930 TI - Transcriptional regulation of the c-jun gene by retinoic acid and E1A during differentiation of F9 cells. AB - Differentiation of mouse F9 embryonal carcinoma (EC) cells can be induced by exposure to retinoic acid (RA) or by expression of adenovirus E1A. The transcription of the c-jun gene is stimulated by either RA or E1A. We report here that both RA and E1A strongly induce the expression of chloramphenicol acetyltransferase (CAT) from c-jun promoter/CAT reporter construct (c-jun/CAT), which is stably integrated into F9 cells, in a manner that is independent of both copy number and integration locus. The induction of c-jun/CAT expression is observed in undifferentiated F9 cells, but not in differentiated F9 cells, adenovirus-infected F9 cells or HeLa cells. Deletion analysis of the promoter region of the c-jun gene indicates that the sequence elements required for the RA and E1A-mediated induction are identical and they have been defined as a region of 145 bp between -190 and -46 of the 5' flanking region of c-jun. This RA and E1A response element (RERE) contains five variants of the motif CGCGGTGACGNT. The upstream two motifs are adjacent and extend in opposite directions, creating an imperfect palindrome. The downstream four motifs are located at 35 or 36 bp intervals in the same orientation. Substitution and insertion analysis indicates that these motifs and their regular intervals are important for the activity of the RERE. PMID- 1310932 TI - Retroviral integration into minichromosomes in vitro. AB - We describe here the use of chromatin as a target for retroviral integration in vitro. Extracts of cells newly infected with murine leukemia virus (MLV) provided the source of integration activity, and yeast TRP1ARS1 and SV40 minichromosomes served as simple models for chromatin. Both minichromosomes were used as targets for integration, with efficiencies comparable with that of naked DNA. In addition, under some reaction conditions the minichromosomes behaved as if they were used preferentially over naked DNAs in the same reaction. Mapping of integration sites by cloning and sequencing recombinants revealed that the integration machinery does not display a preference for nucleosome-free, nuclease sensitive regions. The distributions of integration sites in TRP1ARS1 minichromosomes and a naked DNA counterpart were grossly similar, but in a detailed analysis the distribution in minichromosomes was found to be significantly more ordered: the sites displayed a periodic spacing of approximately 10 bp, many sites sustained multiple insertions and there was sequence bias at the target sites. These results are in accord with a model in which the integration machinery has preferential access to the exposed face of the nucleosomal DNA helix. The population of potential sites in chromatin therefore becomes more limited, in a manner dictated by the rotational orientation of the DNA sequence around the nucleosome core, and those sites are used more frequently than in naked DNA. PMID- 1310933 TI - Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. AB - Repression of transcription from densely methylated genes can be mediated by the methyl-CpG binding protein MeCP-1 (Boyes and Bird, 1991). Here we have investigated the effect of methylation on genes with a low density of methyl-CpG. We found that sparse methylation could repress transfected genes completely, but the inhibition was fully overcome by the presence in cis of an SV40 enhancer. Densely methylated genes, however, could not be reactivated by the enhancer. In vitro studies showed that the sparsely methylated genes bound weakly to MeCP-1 and that binding interfered with transcription. In the absence of available MeCP 1, methylation had minimal effects on transcription. From these and other results we propose that sparsely methylated genes form an unstable complex with MeCP-1 which prevents transcription when the promoter is weak. This complex can be disrupted by a strong promoter, thereby allowing the methylated gene to be transcribed. PMID- 1310934 TI - A ubiquitin conjugating enzyme encoded by African swine fever virus. AB - The post-translational modification of proteins by covalent attachment of ubiquitin occurs in all eukaryotes by a multi-step process. A family of E2 or ubiquitin conjugating (UBC) enzymes catalyse one step of this process and these have been implicated in several diverse regulatory functions. We report here the sequence of a gene encoded by African swine fever virus (ASFV) which has high homology with UBC enzymes. This ASFV encoded enzyme has UBC activity when expressed in Escherichia coli since it forms thiolester bonds with [125I]ubiquitin in the presence of purified ubiquitin activating enzyme (E1) and ATP, and subsequently transfers [125I]ubiquitin to specific protein substrates. These substrates include histones, ubiquitin and the UBC enzyme itself. The ASFV encoded UBC enzyme is similar in structure and enzyme activity to the yeast ubiquitin conjugating enzymes UBC2 and UBC3. This is the first report of a virus encoding a functionally active UBC enzyme and provides an example of the exploitation of host regulatory mechanisms by viruses. PMID- 1310935 TI - Drosophila UbcD1 encodes a highly conserved ubiquitin-conjugating enzyme involved in selective protein degradation. AB - Ubiquitin-dependent selective protein degradation serves to eliminate abnormal proteins and provides controlled short half-lives to certain cellular proteins, including proteins of regulatory function such as phytochrome, yeast MAT alpha 2 repressor, p53 and cyclin. Moreover, ubiquitin-dependent proteolysis is thought to play an essential role during development and in programmed cell death. We have cloned a gene from Drosophila melanogaster, UbcD1, coding for a protein with striking sequence similarity to the yeast ubiquitin-conjugating enzymes UBC4 and UBC5. These closely related yeast enzymes are known to be central components of a major proteolytic pathway of Saccharomyces cerevisiae. By doing a precise open reading frame replacement in the yeast genome we could show that the Drosophila UbcD1 enzyme can functionally substitute for yeast UBC4. UbcD1 driven by the UBC4 promoter rescues growth defects and temperature sensitivity of yeast ubc4 ubc5 double mutant cells. Moreover, expression of UbcD1 restores proteolysis proficiency in the ubc4 ubc5 double mutant, indicating that the Drosophila enzyme also mediates protein degradation. This structural and functional conservation suggests that the UbcD1-UBC4-UBC5 class of enzymes defines a major proteolytic pathway in probably all eukaryotes. PMID- 1310936 TI - Inter-protein distances within the large subunit from Escherichia coli ribosomes. AB - Selected pairs of protonated ribosomal proteins were reconstituted into deuterated 50S subunits from Escherichia coli ribosomes. The rRNA of the deuterated ribosomal matrix was derived from cells grown in 76% D2O, the deuterated protein moiety from cells grown in 84% D2O. This procedure warrants that the coherent neutron scattering of deuterated proteins and rRNA is nearly the same and equals that of a D2O solution of approximately 90%. The neutron scattering is recorded in a reconstitution buffer containing approximately 90% D2O. The result is a significant improvement of the coherent signal:noise ratio over traditional methods; due to this dilute solutions can be used, thus preventing unfavorable inter-particle effects. From the diffraction pattern the distance between the mass centers of gravity of the two protonated proteins can be deduced. In this way, 50 distances between proteins within the large subunit have been determined which provide a basis for future models of the large ribosomal subunit describing the spatial distribution of the ribosomal proteins. A model containing seven ribosomal proteins is presented. PMID- 1310939 TI - NOE and two-dimensional correlated 1H-NMR spectroscopy of cytochrome c' from Chromatium vinosum. AB - 1H two-dimensional (nuclear Overhauser effect spectroscopy (NOESY) and two dimensional correlated spectroscopy (COSY) spectra of cytochrome c' from Chromatium vinosum have been obtained. The protein is of medium size (Mr 28,000), essentially high spin (S = 5/2) although some quantum mechanical spin admixing with S = 3 2 may be present. Under these circumstances NOESY cross peaks have been revealed between geminal protons (alpha-CH2 propionate and beta-CH2 protons of the bound histidine) and between alpha-CH2 propionate protons and the heme methyl groups. COSY maps have confirmed the geminal nature of the proton pairs, even with a linewidth as large as 900 Hz; the J value is about 12 Hz. This assignment has rationalized on a sound basis the biochemical behavior of this protein with pH and has showed the utility of this kind of spectroscopy for the other cytochromes c' structures and analogous systems. PMID- 1310937 TI - A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. AB - Biogenic amines such as serotonin elicit or modulate a wide range of behaviours by interacting with multiple receptor subtypes. We have isolated cDNA clones encoding three distinct Drosophila serotonin receptors which belong to the G protein-coupled receptor family. When expressed in mammalian cells, these receptors activate different intracellular effector systems. The 5HT-dro1 receptor stimulates adenylate cyclase while the 5HT-dro2A and the 5HT-dro2B receptors inhibit adenylate cyclase and activate phospholipase C. Expression of all three receptors starts in late embryos and is restricted to distinct populations of cells in the central nervous system. The 5HT-dro2A receptor is predominantly expressed in midline motor neurons (VUM neurons) that innervate larval muscles thus suggesting a role for this receptor in motor control. PMID- 1310940 TI - A comparative study on the catalytic properties of guanyl-specific ribonucleases. AB - The kinetic parameters of reactions catalyzed by four guanyl-specific RNases T1, Pb1, Th1 and Sa were studied comparatively using three types of substrates; guanosine-2',3'-cyclophosphates, GpN dinucleoside phosphates and synthetic polyribonucleotides. The kinetic parameters were shown to be similar in spite of considerable differences in primary structures of these RNases, including amino acid residues of the active sites. Therefore, primary structures of guanyl RNases allow for a considerable number of substitutions (both in the 'recognising' and catalytical parts of the active site) without changes in the catalytical parameters. PMID- 1310941 TI - Evidence against a role for phosphorylation/dephosphorylation in the regulation of acyl-CoA:cholesterol acyl transferase. AB - 1. As detailed below, we have been able to reproduce observations of time dependent changes in the activity of acyl-CoA:cholesterol acyl transferase (ACAT) in rat liver microsomes, that were suggested to represent evidence of a role for reversible phosphorylation in the regulation of cholesterol ester formation. 2. ACAT in washed rat liver microsomes was inactivated in a time-dependent manner in the presence of Mg2+. However, this effect of Mg2+ appears to be caused by aggregation of microsomal vesicles rather than dephosphorylation, since it could be abolished by rehomogenization, and was mimicked by Ca2+, another agent which causes aggregation. Fluoride did not prevent this effect of Mg2+, but masked it by causing a rapid activation that appeared to be a non-specific effect of increased ionic strength. 3. Under conditions where other proteins were rapidly dephosphorylated, microsomal ACAT activity from rat liver was not affected by incubation with the purified catalytic subunits of protein phosphatases 1, 2A or 2C. Similar results were obtained using protein phosphatases 1 or 2A on microsomes from a macrophage cell line (J774.2 cells). Incubation of cultured J774.2 cells with a cell-permeable inhibitor of these two protein phosphatases, okadaic acid, also had no effect on cholesterol ester formation. 4. A high-speed centrifugation supernatant fraction (S303) from rat liver activated ACAT in the presence of MgATP. This effect was not abolished by prior heat-treatment of the fraction, and the supernatant fraction could not be replaced by purified AMP activated protein kinase or a variety of other protein kinases. 5. The results above were obtained using assays involving endogenous cholesterol as the substrate. The MgATP-dependent activation by S303 was reduced or abolished when the assays were carried out in the presence of the detergent Triton WR-1339 plus cholesterol, or detergent alone. 6. These results do not support the idea that ACAT is regulated by reversible phosphorylation. The most likely explanation for the effect of S303 is that it is an artefact caused by changes in the availability of endogenous cholesterol to the enzyme. PMID- 1310938 TI - GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae. AB - Elevated dosage of the GAC1 gene from the yeast Saccharomyces cerevisiae causes hyperaccumulation of glycogen whereas a gene disruption of GAC1 results in reduced glycogen levels. Glycogen synthase is almost entirely in the active, glucose 6-phosphate-independent, form in cells with increased gene dosage of GAC1 whereas the enzyme is mostly in the inactive form in strains lacking GAC1. GAC1 encodes an 88 kDa protein that is similar to the regulatory subunit (RG1) of phosphoprotein phosphatase type 1 (PP-1) from skeletal muscle that targets PP-1 to glycogen particles. Taken together, these results suggest that GAC1 encodes a regulatory subunit of PP-1. As previously shown for glycogen phosphorylase (GPH1), GAC1 RNA accumulates concomitantly with the appearance of glycogen. A strain with a mutation in the regulatory subunit of the cAMP-dependent protein kinase (bcy1) fails to accumulate GPH1 and GAC1 RNA. These results point to coordinate regulation of enzymes involved in glycogen metabolism at the level of RNA accumulation and indicate that at least part of this control is exerted by the RAS-cAMP pathway. PMID- 1310942 TI - Structural analysis of a novel sialic-acid-containing trisaccharide from Rhodobacter capsulatus 37b4 lipopolysaccharide. AB - Sialic-acid-containing lipopolysaccharides from Rhodobacter capsulatus 37b4 (S form lipopolysaccharide), KB-1 (R-type lipopolysaccharide) and Sp 18 (deep R-type lipopolysaccharide) were investigated for the linkage and substitution of sialic acids. Methylation analysis and behaviour towards acid and enzymic hydrolysis indicated a non-reducing terminal location of sialic acids in the R-type lipopolysaccharide of strain Sp 18, whereas an internal, chain-linked location of sialic acids was found in the lipopolysaccharides of strains 37b4 and KB-1. For these latter strains, methylation analysis revealed a substitution of sialic acids by other sugars at position 7 for strain 37b4 and positions 4 and 7 for strain KB-1. In accordance with the chain-linked position of sialic acids, mild hydrolysis of R. capsulatus 37b4 lipopolysaccharide with acetic acid released a trisaccharide with sialic acid at the reducing terminus. Structural investigation of this trisaccharide by methylation analysis, 1H- and 13C-NMR spectroscopy revealed the presence of the disaccharide Gal1-6Glc at the non-reducing end, probably with an alpha-anomeric configuration of the galactose residue, i.e. melibiose, beta-glycosidically linked to position 7 of sialic acid. Therefore the structure Gal alpha 1-6Glc beta 1-7Neu5Ac is proposed for this core oligosaccharide from R. capsulatus 37b4 lipopolysaccharide. PMID- 1310943 TI - The thyroliberin receptor interacts directly with a stimulatory guanine nucleotide-binding protein in the activation of adenylyl cyclase in GH3 rat pituitary tumour cells. Evidence obtained by the use of antisense RNA inhibition and immunoblocking of the stimulatory guanine-nucleotide-binding protein. AB - The thyroliberin receptor in GH3 pituitary tumour cells is known to couple to phospholipase C via a guanine-nucleotide-binding protein (G protein). Thyroliberin is postulated also to activate adenylyl cyclase, via the stimulatory G protein (Gs). In order to study this coupling, we constructed an antisense RNA expression vector that contained part of the Gs alpha-subunit cDNA clone (Gs alpha) in an inverted orientation relative to the mouse metallothionein promoter. The cDNA fragment included part of the coding region and all of the 3' non translated region. Transient expression of Gs alpha antisense RNA in GH3 cells resulted in the specific decrease of Gs alpha mRNA levels, followed by decreased Gs alpha protein levels. Thyroliberin-elicited adenylyl cyclase activation in membrane preparations showed a reduction of up to 85%, whereas phospholipase C stimulation remained unaffected. Activation of adenylyl cyclase by vasoactive intestinal peptide was reduced by 30-40%. Investigation of the effects of thyroliberin and vasoactive intestinal peptide on adenylyl cyclase in GH3 cell membranes pretreated with antisera against Gs alpha and Gi-1 alpha/Gi-2 alpha support the results obtained by the use of the antisense technique. We conclude that thyroliberin has a bifunctional effect on GH3 cells, in activating adenylyl cyclase via Gs or a Gs-like protein in addition to the coupling to phospholipase C. PMID- 1310944 TI - Subunit composition of the untransformed glucocorticoid receptor in the cytosol and in the cell. AB - We have used bifunctional reagents to examine the subunit composition of the non DNA-binding form of the rat and human glucocorticoid receptor. Treatment of intact cells and cell extracts with a reversible cross-linker, followed by electrophoretic analysis of immunoadsorbed receptor revealed that three proteins of apparent approximate molecular masses, 90, 53 and 14 kDa are associated with the receptor. The first of these was identified immunochemically as a 90-kDa heat shock protein (hsp90). The complex isolated from HeLa cells contained 2.2 mol hsp90/mol steroid-binding subunit. Cross-linking of the receptor complex in the cytosol completely prevented salt-induced dissociation of the subunits. The cross linked receptor was electrophoretically resolved into two oligomeric complexes of apparent molecular mass 288 kDa and 347 kDa, reflecting the association of the 53 kDa protein with a fraction of the receptor. Since no higher oligomeric complexes could be generated by cross-linking cell extracts under different conditions, we conclude that most of the untransformed cytosolic receptor is devoid of additional components. PMID- 1310945 TI - Effect of environmental complexity on the latency of cortical vibrissa potentials. AB - The effect of differential rearing on evoked potentials was studied in the vibrissal representation of the rat neocortex. Young rats were reared in either enriched, standard, or impoverished conditions from the age of 24-25 days. At 55 60 days of age, the epicortical responses to electric stimulation of a whisker follicle were analyzed under urethane anesthesia. Slight but significant shortening of the latency of initial positivity in the evoked potential was observed after rearing in the enriched condition as compared to the data obtained from the littermates that were reared in the standard or impoverished conditions. PMID- 1310946 TI - Protein-protein interactions at a DNA replication fork: bacteriophage T4 as a model. AB - The DNA replication system of bacteriophage T4 serves as a relatively simple model for the types of reactions and protein-protein interactions needed to carry out and coordinate the synthesis of the leading and lagging strands of a DNA replication fork. At least 10 phage-encoded proteins are required for this synthesis: T4 DNA polymerase, the genes 44/62 and 45 polymerase accessory proteins, gene 32 single-stranded DNA binding protein, the genes 61, 41, and 59 primase-helicase, RNase H, and DNA ligase. Assembly of the polymerase and the accessory proteins on the primed template is a stepwise process that requires ATP hydrolysis and is strongly stimulated by 32 protein. The 41 protein helicase is essential to unwind the duplex ahead of polymerase on the leading strand, and to interact with the 61 protein to synthesize the RNA primers that initiate each discontinuous fragment on the lagging strand. An interaction between the 44/62 and 45 polymerase accessory proteins and the primase-helicase is required for primer synthesis on 32 protein-covered DNA. Thus it is possible that the signal for the initiation of a new fragment by the primase-helicase is the release of the polymerase accessory proteins from the completed adjacent fragment. PMID- 1310947 TI - Calcium and the heart: exchange at the tissue, cell, and organelle levels. AB - Cellular calcium (Ca) exchange in arterially perfused whole heart is markedly perfusion-limited. Therefore, a large fraction of exchangeable Ca recycles within the cell before exchanging with extracellular Ca. Ca enters the cell via sarcolemmal (SL) transient (T) and long-lasting (L) channels activated at more negative and less negative membrane potential, respectively. The larger L currents are controlled via phosphorylation and G protein interaction to provide Ca to induce Ca release from sarcoplasmic reticulum (SR) and for direct myofilament activation. Troponin C (TNC) binds 3 mol of Ca/mol. Only the low affinity site is responsible for activation of force and regulation of myofilament ATPase rate. This occurs through a shift in troponin I (TNI) with respect to actin induced by the TNC Ca binding. Relaxation depends on reduction of cytosolic (Ca) and occurs via 1) Ca pumping into the longitudinal SR modulated by phospholamban; 2) the recently cloned high-capacity electrogenic SL Na-Ca exchanger; and 3) the SL Ca pump under complex regulation including calmodulin control. Mitochondria transport Ca, but this transport is directed primarily to the regulation of various Ca-sensitive dehydrogenases so that oxidative metabolism can be adjusted to changes in energy demand. The regulation of Ca movements consumes about 25% of the cell's total energy output. Mitochondrial Ca exchanges with extracellular Ca most slowly (t 1/2 = 3.6 min), SR Ca quite rapidly (t 1/2's = 3 and 19 s), and an Na-Ca exchange-dependent compartment very rapidly (t 1/2 = 500 ms). After further description of Ca handling by the individual organelles, Ca movement is followed through the cell during the course of contraction, and the contribution of each organelle or compartment to overall cellular Ca exchange is defined. PMID- 1310948 TI - Endoscopic ultrasound for localisation of islet cell tumours. AB - In a prospective study endoscopic ultrasound localisation of pancreatic endocrine tumours was attempted in 21 patients with clinically suspected islet cell tumours. Most patients were referred after the failure of conventional imaging methods. Endoscopic ultrasound correctly identified the site of 12 of 15 insulinomas, one glucagonoma, and a diffuse pancreatic abnormality in a patient with multiple endocrine adenopathy. There were two true negative examinations and one technical failure. The sensitivity of endoscopic ultrasound was much greater than that of computed tomography or conventional transabdominal ultrasonography. PMID- 1310949 TI - Overview of screening and management of familial adenomatous polyposis. AB - The rarity of familial adenomatous polyposis (FAP) means that many clinicians may be unaware of the major advances that have taken place in screening for the condition over the past five years. This review is not only to document the current scene but also to give details of those involved in establishing registries throughout the country. FAP is a hereditary disorder which carries with it almost a 100% risk of colorectal cancer. The aim of screening is to detect gene carriers before they present with symptoms attributable to colonic polyps. In this way the incidence of colorectal cancer can be greatly reduced. The use of gene probes to identify patients with FAP is in its infancy but in selected pedigrees gene carriers can be identified using a venous blood sample. The recognition that congenital hypertrophy of the retinal pigment epithelium is an extracolonic manifestation of FAP in most pedigrees allows non-invasive ophthalmological screening of relatives at risk. The combination of these new screening methods with an effective regional registry for FAP can increase the number of patients detected by screening rather than by symptoms. This facilitates appropriate prophylactic surgery and reduces mortality related to colorectal cancer. PMID- 1310951 TI - B-cell lymphoproliferative disorders in solid-organ transplant patients: detection of Epstein-Barr virus by in situ hybridization. AB - B-cell lymphoproliferative disorders (BLPDs) occur in approximately 2% of transplant recipients and are frequently fatal. Indirect serologic evidence has implicated Epstein-Barr virus (EBV) as an etiologic factor in these lesions. Direct evidence of the presence of EBV in these lesions has been obtained in relatively few cases. We used in situ hybridization (ISH) with a probe for the BamHI-W region of the EBV genome to study 52 tissue specimens from 28 solid-organ transplant patients who had BLPD. Epstein-Barr virus-infected lymphoid cells were identified in 26 of these 28 patients. The two patients without ISH evidence of EBV infection showed no distinctive clinical, morphologic, or serologic features. Previous filter-hybridization studies of these two patients had demonstrated evidence of EBV infection. Seven additional transplant patients without evidence of BLPD were studied as controls and showed no evidence of EBV in their lymphoid cells by ISH. These data provide further support for the etiologic role of EBV in the pathogenesis of posttransplantation lymphoproliferative disorders. PMID- 1310950 TI - Human papillomavirus type 16 and 18 gene expression in cervical neoplasias. AB - Human papillomavirus (HPV) types 16 and 18 are strongly implicated in the generation of progressive cervical neoplasms. The viruses produce complex families of overlapping messenger RNAs that are linked to differentiation, making it necessary to analyze gene expression in the context of morphology. We have developed HPV type 16 and type 18 subgenomic clones from which 3H-labeled riboprobes specific to individual mRNA families can be generated in vitro. Using these probes for in situ hybridization, we examined serial sections of archival biopsy specimens of the spectrum of genital lesions. In low-grade squamous lesions, all viral open reading frames were expressed, and the most abundant transcription spanned the E4 and E5 open reading frames at the 3' end of the E region. L region transcription coding for the capsid proteins was restricted to terminally differentiated keratinocytes. As the grade of neoplasia increased, cellular differentiation and overall viral transcription decreased and, with few exceptions, the L2 and L1 transcripts ceased to exist. The E6-E7 transforming region was invariably derepressed. Interestingly, the patterns of HPV-16 gene expression suggested the coexistence of episomal and integrated viral DNAs. In contrast, in HPV-18 lesions, all the viral template DNA appeared to have integrated. Integration was deduced to have occurred near the boundary of the E1 and E2 open reading frames. Viral transcription patterns were similar in carcinomas in situ and in invasive carcinomas, regardless of the histologic cell types or the associated virus types, consistent with the notion that additional host gene alterations were necessary for progression. On the basis of viral gene expression in vivo and the E6 promoter regulation previously characterized in vitro, we discuss a molecular mechanism for HPV-associated carcinogenesis. PMID- 1310952 TI - Demonstration of human papillomavirus DNA in a peripheral ameloblastoma by in situ hybridization. AB - The peripheral ameloblastoma (PA) is a rare, extraosseous, odontogenic lesion usually located on the mandibular or maxillary gingiva. It often appears as an asymptomatic, firm, pink-red nodule with occasional secondary involvement of the underlying bone. Although histologically identical to primary intraosseous ameloblastoma, the PA is notably less aggressive in biologic behavior and rarely recurs following conservative treatment. It has a proposed dual histogenesis, while its etiology remains obscure. Several benign oral mucosal lesions have been found to be associated with various types of human papillomavirus (HPV). The following study uses a commercially available HPV DNA in situ hybridization technique to confirm the presence of HPV in a previously reported case of PA. Results were positive for HPV types 16/18 but negative for HPV types 6/11. The implications of these results with regard to etiology are discussed. PMID- 1310953 TI - Neural invasion in intraductal carcinoma of the breast. AB - Although perineural invasion in a malignancy favors the diagnosis of invasive over in situ carcinoma, we report a case of cribriform intraduct carcinoma of the breast showing perineural invasion. The in situ nature of the lesion is supported by the finding of an intact actin-positive myoepithelial cell layer around the cribriform growths and the preservation of lobular architecture. PMID- 1310954 TI - Genetic localization of Hao-1, blind-sterile (bs), and Emv-13 on mouse chromosome 2. AB - The blind-sterile (bs) mutation in the mouse was localized on Chromosome 2 between Hao-1 and Emv-13. N2 progeny from a backcross between congenic female 129.AKR-bs Emv-13 mice and (129.AKR-bs/bs x Mus musculus molossinus) F1 male mice were typed by analysis of isozyme variants for Hao-1, visible inspection for bs, and restriction fragment length polymorphism for Emv-13 and Emv-15. Comparison between markers on mouse Chromosome 2 and corresponding markers on human chromosomes suggest that the human homolog of bs will be located on 20q11-q13. PMID- 1310955 TI - The severity of herpes simplex viral keratitis in mice does not reflect the severity of disease in humans. AB - Four herpes simplex type 1 virus (HSV) isolates were selected from patients with mild ocular disease and four from patients with severe ocular disease on the basis of the number of epithelial recurrences, presence or absence of stromal disease, visual acuity, and the need for corneal transplantation. The scarified right corneas of 20 BALB/c mice were inoculated with each low-passage HSV isolate (1.0 x 10(7) plaque-forming units/ml) and examined three times per week for 2 weeks for the presence and severity of epithelial and stromal disease. The eight individual virus isolates differed with respect to the incidence of dendritic disease (P less than 0.001), the severity of dendritic disease (P less than 0.001), the incidence of stromal disease (P = 0.002), and the severity of stromal disease (P = 0.001) they produced in the mouse. The severity of disease was compared for the two groups of viruses: (1) those that had caused mild disease in their human hosts and (2) those that had caused severe disease. There were no statistically significant differences in the severity or incidence (44 versus 43 animals, respectively) of dendritic disease or stromal disease (27 of 80 animals in each group) between the two groups. These data suggest that the naive BALB/c mouse model of acute HSV keratitis after topical ocular inoculation does not reflect clinically significant differences in the severity of human HSV keratitis that might be caused by variations in the virus genome. PMID- 1310956 TI - The influence of cyclic AMP upon Na,K-ATPase activity in rabbit ciliary epithelium. AB - ATPase activity was measured in samples of freshly dissected rabbit ciliary epithelium. The epithelium was ruptured in distilled water, frozen briefly, and incubated at 37 degrees C in a buffer containing 100 mM NaCl and 32P-labeled adenosine triphosphate (ATP). The rate of ATP hydrolysis by the epithelium was linear for as long as 45 min. Ouabain (1 mM) reduced the ATP hydrolysis rate by approximately 50%. When the epithelium was preincubated for 10 min. in the presence of 1 mM dibutyryl cyclic adenosine monophosphate (cAMP), the ouabain sensitive (Na,K-ATPase) activity was diminished; ouabain-insensitive ATPase activity was not reduced. Preincubation of the epithelium with forskolin with isobutylmethylxanthine also reduced ouabain-sensitive ATPase activity. These observations suggest that the ciliary epithelium may have a mechanism for short term modulation of Na,K-ATPase activity by cAMP. Such a mechanism could be linked to the ability of cAMP-dependent protein kinase to reduce Na,K-ATPase activity in the tissue. PMID- 1310957 TI - Detection of Epstein-Barr virus sequences in patients with Kawasaki disease by means of the polymerase chain reaction. AB - We used a selective DNA amplification technique to detect Epstein-Barr virus (EBV) DNA in peripheral blood mononuclear cells from patients with Kawasaki disease (KD). By means of the polymerase chain reaction EBV sequences were indentified directly in 21 (60%) of 35 KD patients within 2 weeks after the onset of KD. Furthermore, EBV sequences were detected in all of 6 repeatedly tested patients with KD within 3 months after disease onset. In contrast, only 2 (12%) of 17 control DNA samples were polymerase chain reaction positive. These results indicate that an unusual EBV-cell interaction may exist in KD. PMID- 1310959 TI - NCI Proton Workshop: Potential Clinical Gains by Use of Superior Radiation Dose Distribution. PMID- 1310958 TI - HeLa cells grown continuously in protein-free medium: a novel model for the study of virus replication. AB - Human carcinoma of the cervix cell line HeLa, adapted to continuous growth in a protein-free chemically defined medium, was used as substrate for the replication of several human pathogenic viruses. Growth characteristics of the cells designated as HeLa-PF in protein-free 1:1 nutrient mixture of Dulbecco's modified MEM and Ham's F-12 supplemented with L-ascorbic acid 2-phosphate were similar to those of the cells grown in a serum-supplemented medium. After 30 months (135 subcultures) in the protein-free medium, HeLa-PF cells were infected with poliovirus types 1, 2 and 3; adenovirus types 2 and 5 and herpes simplex virus type 1. Both adenoviruses and polioviruses developed in HeLa-PF cells titers and showed cytopathic effects comparable to those obtained in conventionally grown and maintained cells; in contrast, significantly lower herpes simplex virus type 1 titers and changed characteristics of the cytopathic effects were observed in HeLa-PF cells. The results show that HeLa-PF cells grown continuously in protein free medium provide a unique system for the study of virus replication. PMID- 1310960 TI - NCI Proton Workshop. Potential clinical gains by use of superior radiation dose distribution. PMID- 1310961 TI - Strategy for planned radiotherapy of malignant gliomas: postoperative treatment with combinations of high dose proton irradiation and tumor seeking radionuclides. AB - A strategy for improved treatment of malignant gliomas grade III-IV is presented. The strategy can briefly be described as surgical removal of the bulky tumor, high precision external irradiation of small brain volumes over and near the primary tumor area with high doses from proton beams, and thereafter treatment of spread cells with toxic radionuclides. Proton beams suitable for this are under development. The clinical effects of high single doses on malignant gliomas grade III-IV are presently tested with conventional gamma radiation. Targeting of spread glioma cells with toxic radionuclides tagged to epidermal growth factor, EGF, or to EGF-dextran is presently tested in experimental systems and can, in the near future, be tested in combination with local high doses of external proton radiation. The possibilities to combine proton beams with EGF-guided neutron capture therapy will be considered in a longer perspective. PMID- 1310962 TI - Comparative treatment planning: proton vs. x-ray beams against glioblastoma multiforme. AB - The survival of patients with glioblastoma multiforme is extremely poor, the 5 year survival rate being almost zero. The cause of failure is almost exclusively local progression of tumor, the remainder is due to complications of treatment. Although this tumor is clearly radiation resistant, there is evidence of a dose response relationship. Using a thin slice CT scan of the entire head of a patient with glioblastoma multiforme, 3-dimensional radiation treatment plans were developed for treatment to a dose of 90 cobalt-Gray-equivalent (CGE). Dose distributions using protons were compared to those using x-rays. The results showed advantages for the proton beam technique. Namely the proton plan irradiated less non-target brain than the x-ray plan; this was especially so in the decrease of coverage of deep-seated structures. The volume of non-target brain that received more than 70 CGE was 175 ml for the x-ray plan and 94 ml for the proton plan. This study indicates that for a subpopulation of patients with glioblastoma multiforme, at least 90 CGE could be delivered with proton beam techniques to the target with only small volumes of normal brain structures receiving more than 70 CGE. PMID- 1310963 TI - Potential clinical gain of proton (and heavy ion) beams for brain tumors in children. PMID- 1310964 TI - Role for proton beam irradiation in treatment of pediatric CNS malignancies. AB - The ability to vary the proton energy (depth of beam penetration) and modulate the dose distribution at the end of range permits delivery of an increased dose to the designated cancer-containing volume with a reduced dose to overlying normal brain tissue. The evolution of childhood CNS malignancy following therapy is reviewed to identify radiation response variables indicating where the proton dose distribution will improve the therapeutic ratio. The review documents that of the 1262 children expected to develop CNS malignancy in 1989, only 43% will survive 5 years. About 75% of those with medulloblastoma and over 90% with astrocytoma die from persistent (in-field) disease. When the patient has been treated with radiation, it is accepted that disease persistence indicates the cancer dose was insufficient. Potentially 536 children could show an improved incidence of local control and improved survival from an increased cancer dose available from proton irradiation. As the total dose and volume of brain irradiated is increased about 1800 cGy, brain dysfunction increases, producing a spectrum of functional and intellectual deficits which are age and volume related. About 900 irradiated patients would have fewer in-field histologic and functional changes if the dose to normal brain, or the volume of brain irradiated, is reduced by an improved dose distribution. A proton beam treatment plan, delivering a cancer dose of 7400 cGy, is simulated for a thalamic astrocytoma. The dose distribution of this plan is compared with an x-ray plan used to treat a patient, in which a dose of 5400 cGy was delivered to the astrocytoma. Comparative isodose distributions and dose-volume histograms indicate a decreased integral dose to normal brain and a decreased volume of normal brain irradiated, even as the cancer dose is boosted 2000 cGy with protons. PMID- 1310965 TI - Potential improvement of three dimension treatment planning and proton therapy in the outcome of maxillary sinus cancer. AB - Carcinomas arising in the maxillary sinus are challenging technical problems for radiotherapists due to the complexity of the regional anatomy and the close relations of the tumor to dose-limiting critical structures (eyes, optic nerves, optic chiasm, and brain stem). This study shows that an improvement in the dose distribution can be achieved with the use of three dimensional treatment planning and a combination of x-ray and proton beam arrangements. Although tumor coverage was identical when comparing dose distributions of X rays alone to X rays plus proton beam boost, the critical structures received less dose in the X rays plus proton beam plan. Because a superior dose distribution should yield an improved local control and reduced morbidity, a benefit in survival could be expected. PMID- 1310966 TI - Carcinoma of the tonsillar region: potential for use of proton beam therapy. AB - An investigation of treatment results in tonsillar region carcinomas was conducted, with particular attention to local control and morbidity from current therapy. The purpose of the investigation was to identify problems that might be resolvable with a superior treatment modality. A search was made of the National Library of Medicine's MEDLINE database, covering local control, survival, and morbidity from current therapies; dose-response relationships; and prognostic indicators. Three-dimensional radiotherapy plans were developed for representative cases, comparing photon-beam plans with proton-beam plans. Locoregional control is a major problem, and morbidity from standard therapy is high. Comparative treatment plans reveal that proton beams can deliver higher doses to the tumor volume, with significantly reduced radiation to salivary glands and mandible, than can photon-beam irradiation. The absorption and distribution characteristics of protons provide the radiation oncologist with a superior tool for treating patients with tonsillar region carcinomas. The therapeutic advantage accrues from these superior characteristics, not from an inherent biologic advantage. PMID- 1310967 TI - Indications of particle radiation therapy in the treatment of carcinoma of the esophagus. AB - Studies were made to evaluate the role of radiations in the treatment of carcinoma of the esophagus to confirm indications for charged particles. Results of the studies showed that prognosis of the patients treated with radiations depend strongly on length of tumor as well as on invasion of tumor cells into the adventitia of the esophagus. It was concluded that patients suffering from carcinoma of the esophagus less than 8 cm length are indicated for particle radiations. PMID- 1310968 TI - CCRT (computer controlled radiation therapy) for non-small cell lung cancer: sensitivity of clinical gains to organ tolerance restrictions. AB - A method is described for allowing the entrance angles of beams to vary along the longitudinal axis of the target volume using a computer controlled radiation therapy (CCRT) treatment technique. The increase in tumor dose potentially available with this technique is evaluated for the case of a non-small cell carcinoma of the lung for which treatment is constrained by a clinically relevant tolerance condition. Tolerance is expressed in terms of that volume of unaffected contralateral lung allowed to receive greater than 20 Gy. The evaluation is repeated with small changes made to the constraining condition in order to explore the sensitivity of the dose gain to the definition of tolerance. For the chosen example, at least an additional 10 Gy could be prescribed to the tumor with the CCRT technique when the 20 Gy contralateral lung volume was held to less than 30%. A gain of 7 Gy was found when the 20 Gy volume was held to 27% and 1 Gy when the 20 Gy volume was reduced to 25%. CCRT treatment can result in a significant dose gain under a clinically relevant condition for tolerance. Its measured advantage strongly depends on the dose constraints specified. Sensitivity analysis is necessary to meaningfully evaluate the merits of alternative treatment techniques. PMID- 1310969 TI - The potential for proton beam therapy in locally advanced carcinoma of the cervix. AB - Advanced cervix cancer has a local failure rate of 40-45% when treated with a combination of external beam irradiation and intracavitary implants, and approximately 60-65% when treated by external beam irradiation alone. Because of the absorption characteristics of protons, there is the potential for improved dose distributions and delivery of greater total doses to cervical neoplasms. Using computer-modelled examples, this theoretical advantage has been tested and the results have been extrapolated to show a therapeutic advantage in local control and morbidity. The first example shows the use of protons and intracavitary implants in advanced cervix tumors. Larger tumor doses are possible with protons than with photons, while the dose-volume to normal structures is decreased. In the second example, external proton beam treatment alone also reveals significantly higher tumor doses and lower normal tissue doses, compared to photon irradiation. With new proton therapy facilities being designed and built in the United States and overseas, protocols are being designed to evaluate the therapeutic potential of proton therapy in locally advanced cervix cancer. PMID- 1310970 TI - Prospects for proton therapy in carcinoma of the cervix. AB - Carcinoma of the cervix remains a serious problem worldwide. The results of radiation therapy varies from institution to institution, with actuarial 5-year survival rates for Stage IIIB disease of between 28 and 60%. The inferior survival figures can be ascribed to poor local control due to inadequate dosage, partly due to the non-use of intracavitary therapy. Results from the literature were reviewed to assess the optimal dose required to sterilize the primary, para metrial and nodal disease within the pelvis. The aim of this study is to assess whether the target volume could be reduced to allow an increased dose to be delivered. Protons, in view of their physical characteristics, would aid this objective. From CT scans the minimal target volume was determined, and treatment plans for a 200 MeV proton beam were evaluated. It appears that a volume reduction of up to 60% in the target volume may be achieved with proton therapy when compared to the usual target volume achievable with photon therapy, and thus a 20% dose increment may be reasonable. This increased dose may translate to a 40% improvement in the local control rate without an expected increase in complications. An improved local control rate may lead to improved survival. A compatible technique of well-fractionated high dose rate intracavitary therapy (ICT) based on an indwelling intra-uterine tube is offered that will allow up to 10 fractions of ICT with only a single anaesthetic, to be integrated with a similar number of fractions of proton therapy. PMID- 1310971 TI - Potential for gain in the use of proton beam boost to the para-aortic lymph nodes in carcinoma of the cervix. AB - The management of para-aortic lymph nodes (PALN) in carcinoma of the cervix by surgery and adequate conventional radiotherapy (55 Gy +) is associated with an unacceptably high incidence of major morbidity (greater than 30%) discouraging this therapy. The addition of a proton boost to photon treatment will permit the delivery of 60 to 70 Gy to PALN with a morbidity expected to be equal to that observed with 45 Gy photons (13%). The potential for improved control rates at the increased dose may be of the order of 10 to 20% depending on the initial stage of disease. Suitable selection criteria may increase this further in some subgroups. PMID- 1310972 TI - 3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer. AB - To assess the usefulness of proton beams for treatment of patients with rectal cancer, we have performed comparative 3D treatment planning for proton beam and x ray beam therapy. Three common x-ray techniques (AP-PA, 3-field, and 4-field box), a proton beam only plan, and a proton boost plan were compared. The plan which would have been treated without the aid of the 3D planning system was also simulated. Dose distributions were analyzed and dose-volume histograms computed for the target volumes and critical normal tissues. Analyses of these plans demonstrate that the proton beam techniques reduce the volume of small bowel irradiated. This may allow higher doses to be delivered to the tumor, with a probable increase in local control, or a reduction in normal tissue complications probability. All the plans developed with the 3D planning system treated significantly less bowel than the one planned without it. PMID- 1310973 TI - Charged particle therapy to pediatric tumors of the retroperitoneal region: a possible indication. AB - Despite a very successful interdisciplinary therapy regimen for pediatric solid tumors dominated by surgery and chemotherapy, the role of radiotherapy might become again more important if new techniques will allow a better dose localization to the target volume combined with a better protection of the normal tissue. This characteristic is known for charged particle beams. In a field study based on German cooperative trials, the possibility of a charged particle radiotherapy to retroperitoneal tumors of childhood will be discussed regarding indications in risk groups and recurrences. Absolute patient numbers are estimated from the clinical experiences and the incidences of the diseases. A stepwise introduction of this new therapy modality is proposed. PMID- 1310974 TI - Acetylcholine-evoked increase in the cytoplasmic Ca2+ concentration and Ca2+ extrusion measured simultaneously in single mouse pancreatic acinar cells. AB - The intracellular free Ca2+ concentration ([free Ca2+]i) was measured simultaneously with the Ca2+ extrusion from single isolated mouse pancreatic acinar cells placed in a microdroplet of extracellular solution using the fluorescent probes fura-2 and fluo-3. The extracellular solution had a low total calcium concentration (15-35 microM), and acetylcholine (ACh), applied by microionophoresis, therefore only evoked a transient elevation of [free Ca2+]i lasting about 2-5 min. The initial sharp rise in [free Ca2+]i from about 100 nM toward 0.5-1 microM was followed within seconds by an increase in the total calcium concentration in the microdroplet solution ([Ca]o). The rate of this rise of [Ca]o was dependent on the [free Ca2+]i elevation, and as [free Ca2+]i gradually decreased Ca2+ extrusion declined with the same time course. Ca2+ extrusion following ACh stimulation was not influenced by removal of all Na+ in the microdroplet solution indicating that the Ca2+ extrusion is not mediated by Na(+)-Ca2+ exchange but by the Ca2+ pump. The amount of Ca2+ extruded during the ACh-evoked transient rise in [free Ca2+]i corresponded to a decrease in the total intracellular Ca concentration of about 0.7 mM which is close to previously reported values (0.5-1 mM) for the total concentration of mobilizable calcium in these cells. Our results therefore demonstrate directly the ability of the Ca2+ pump to rapidly remove the large amount of Ca2+ released from the intracellular pools during receptor activation. PMID- 1310975 TI - Ca2+ release from inositol trisphosphate-sensitive stores is not modulated by intraluminal [Ca2+]. AB - In a recent model developed to explain the apparent "quantal" nature of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-induced Ca2+ release from specific intracellular stores, it was proposed that Ca2+ release from the stores may itself be modulated by intraluminal levels of Ca2+, possibly via an action at a binding site on the Ins(1,4,5)P3 receptor/Ca2+ channel complex. Essential predictions of this model include a specific effect of intraluminal Ca2+ levels on the sensitivity of Ins(1,4,5)P3-induced Ca2+ release and a non-exponential decay of passive Ca2+ loss from the store following inhibition of the Ca2+ pump on the store. However, in measurements of Ins(1,4,5)P3-induced Ca2+ release and passive Ca2+ loss in permeabilized preparations of a model exocrine cell under conditions of thapsigargin-induced store depletion, we found that neither of these predicted behaviors could be demonstrated. PMID- 1310976 TI - Lysine 480 is not an essential residue for ATP binding or hydrolysis by Na,K ATPase. AB - Lysine 480 has been suggested to be essential for ATP binding and hydrolysis by Na,K-ATPase because it is labeled by reagents that are thought to react with the ATPase from within the ATP binding site. In order to test this hypothesis, Lys 480 was changed to Ala, Arg, or Glu by site-directed mutagenesis, and the resultant Na,K-ATPase molecules were expressed in yeast cells. The ATPase activity of each of the mutants was similar to the activity of the wild type enzyme indicating that Lys-480 is not essential for ATP hydrolysis. The binding of [3H]ouabain in both ATP-dependent and inorganic phosphate-dependent reactions was used to determine the apparent affinity of each mutant for ATP or Pi. The K0.5(ATP) for ouabain binding to phosphoenzyme formed from ATP was 1-3 microM for Lys-480, Arg-480, and Ala-480, whereas for Glu-480 the K0.5(ATP) was 18 microM. The K0.5(Pi) for ouabain binding to phosphoenzyme formed from inorganic phosphate was 16-28 microM for Lys-480, Arg-480, and Ala-480, but was 74 microM for Glu 480. The Kd for ouabain binding was similar for both the wild type and mutant Na,K-ATPase molecules (3-6 nM). These data indicate that the substitution of an acidic amino acid for lysine at position 480 appears to reduce the affinity of the Na,K-ATPase for both ATP and phosphate. It is concluded that Lys-480 is not essential for ATP binding or hydrolysis or for phosphate binding by Na,K-ATPase but is likely to be located within the ATP binding site of the Na,K-ATPase. PMID- 1310977 TI - Alteration of a DNA-dependent ATPase activity in xeroderma pigmentosum complementation group C cells. AB - DNA-dependent ATPase activities in crude extracts prepared from HeLa cells were separated into five peaks by fast protein liquid chromatography Mono Q column chromatography. Similar elution profiles were observed with the extracts from human cells normal in repair and xeroderma pigmentosum cells belonging to complementation groups A through G except for group C. An alteration in elution of one of the five ATPases, designated DNA-dependent ATPase Q1, was observed with a cell line of complementation group C. This alteration was observed with all tested cell lines that belonged to group C. ATPase Q1 in HeLa cell extracts exhibited about 2-fold higher activity with ultraviolet light-irradiated DNA as compared to that with non-irradiated DNA, whereas little difference in the effects of two DNAs was observed with the ATPase activities in the extract from group C cells. PMID- 1310978 TI - DNA-dependent adenosinetriphosphatase C1 from mouse FM3A cells has DNA helicase activity. AB - In our previous study, we identified four chromatographically distinct DNA dependent ATPases, B, C1, C2, and C3, in mouse FM3A cells (Tawaragi, Y., Enomoto, T., Watanabe, Y., Hanaoka, F., and Yamada, M. (1984) Biochemistry 23, 529-533). The DNA-dependent ATPase C1 has been purified and characterized in detail. A divalent cation and a polynucleotide cofactor were required for the ATPase activity. Poly(dT), single-stranded circular DNA, and heat-denatured DNA were very effective. Almost no ATPase activity was observed with S1 nuclease-treated native DNA. ATPase C1 hydrolyzed ATP only among the ribo- and deoxyribonucleoside triphosphates tested, and this fact distinguished ATPase C1 from ATPases B, C2, and C3, because the latter enzymes are capable of hydrolyzing both ATP and dATP. The purified DNA-dependent ATPase C1 fraction was shown to have a DNA helicase activity that was dependent on hydrolysis of ATP. The helicase activity and DNA dependent ATPase activity cosedimented at 5.2 S on glycerol gradient centrifugation. Both activities showed similar preferences for nucleoside 5' triphosphates and similar requirements for divalent cations. The DNA helicase activity was inhibited by the addition of single-stranded DNAs that served as cofactor for the ATPase activity. The efficiency of a single-stranded DNA to inhibit DNA helicase activity correlated well with the capacity of the DNA to serve as cofactor for DNA-dependent ATPase activity. The helicase was shown to migrate along the DNA strand in the 5' to 3' direction, which is the same direction of migration of the mouse DNA helicase B (Seki, M., Enomoto, T., Yanagisawa, J., Hanaoka, F., and Ui, M. (1988) Biochemistry 27, 1766-1771). PMID- 1310980 TI - The yeast plasma membrane H(+)-ATPase. An essential change of conformation triggered by H+. AB - The plasma membrane of Schizosaccharomyces pombe contains an H(+)-ATPase similar to the cation transport ATPases of other eukaryotic organisms. The fluorescence excitation and emission spectra of the purified H(+)-ATPase are characteristic of tryptophan residues. pH reduction from 7.5 to 5.7 produces a 4% decrease in fluorescence intensity, while a further reduction to pH 5.0 leads to an increase of fluorescence. A close correlation is observed between the pH dependence of the intrinsic fluorescence and the pH dependence of (i) ATPase activity, (ii) the fluorescence of Tb-formycin triphosphate bound to the active site, and (iii) inhibition by vanadate of ATPase activity. It is proposed that the effect of pH on intrinsic fluorescence reveals the existence of an H+ induced conformational change of the H(+)-ATPase similar to the E1----E2 transition of the other plasma membrane cation transport ATPases. PMID- 1310979 TI - Alpha 1-adrenergic receptor-mediated activation of phospholipase D in rat cerebral cortex. AB - We have investigated phospholipase D activity in rat brain cortical slices prelabeled with [32P]orthophosphoric acid. In the presence of ethanol (170 mM), norepinephrine stimulated, in a dose-dependent manner (EC50 = 2.2 microM), the accumulation of [32P]phosphatidylethanol as a result of phospholipase D activity. Norepinephrine-stimulated phospholipase D activity was completely inhibited by prazosin, a specific alpha 1-adrenergic antagonist (Ki = 2.8 nM). However, no accumulation of phosphatidylethanol was observed in the presence of the muscarinic agonist carbachol. The Ca2+ ionophore ionomycin and the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) also stimulated [32P]phosphatidylethanol accumulation in cortical slices, in a dose- and time dependent manner, whereas the inactive phorbol, 4 alpha-phorbol 12,13 didecanoate, did not stimulate phospholipase D activity. Staurosporine and 1-(5 isoquinolinylsulfonyl)-2-methylpiperazine, two potent inhibitors of protein kinase C, inhibited PMA and ionomycin stimulation of phospholipase D activity, but did not affect the response to norepinephrine. Furthermore, the effects of PMA and norepinephrine were additive. Differences between PMA and norepinephrine stimulation of phospholipase D activity were also found with regard to the extracellular Ca2+ requirement and time course of phosphatidylethanol accumulation. No stimulation of phospholipase D activity by norepinephrine was observed in slices from cerebellum, a brain area with a low density of alpha 1 adrenergic receptors, while the effect of PMA was greater in the cerebellum than in cortical or hippocampal slices. These results strongly suggest that activation of phospholipase D in cortical slices by norepinephrine and PMA involve different mechanisms. PMID- 1310981 TI - Isolation and characterization of rat 3Y1 fibroblast clones overexpressing the src homology region of phospholipase C-gamma 2. AB - To examine the regulatory function of the src-related SH2 and SH3 (SH2/SH3) region of phospholipase C-gamma 2 (PLC-gamma 2), we expressed this region of rat PLC-gamma 2 cDNA in rat 3Y1 fibroblasts and isolated and characterized a number of clones (approximately 20 clones). An increase of endogenous tyrosine kinase activity was observed in all cell clones that highly expressed a translational product of the SH2/SH3 domain. Moreover, endogenous phosphatidylinositol 4,5 bisphosphate hydrolyzing activity was also enhanced in these clones, and PLC gamma 1 seemed to be preferentially activated among endogenous PLC isozymes. Genistein, an inhibitor of tyrosine kinase, inhibited this activation of PLC gamma 1, and tyrosine phosphorylation was observed on PLC-gamma 1 molecules, indicating the involvement of tyrosine kinases in the PLC-gamma 1 activation. These results suggest that the SH2/SH3 region of PLC-gamma would function as a multidirectional regulator which controls at least two major signaling pathways: tyrosine kinase and phosphatidylinositol 4,5-bisphosphate hydrolysis. PMID- 1310982 TI - Activation of cell surface glucose transporters measured by photoaffinity labeling of insulin-sensitive 3T3-L1 adipocytes. AB - Several studies have demonstrated that the intrinsic catalytic activity of cell surface glucose transporters is highly regulated in 3T3-L1 adipocytes expressing GLUT1 (erythrocyte/brain) and GLUT4 (adipocyte/skeletal muscle) glucose transporter isoforms. For example, inhibition of protein synthesis in these cells by anisomycin or cycloheximide leads to marked increases in hexose transport without a change in the levels of cell surface glucose transporter proteins (Clancy, B. M., Harrison, S. A., Buxton, J. M., and Czech, M. P. (1991) J. Biol. Chem. 266, 10122-10130). In the present work the exofacial hexose binding sites on GLUT1 and GLUT4 in anisomycin-treated 3T3-L1 adipocytes were labeled with the cell-impermeant photoaffinity reagent [2-3H]2-N-[4-(1-azitrifluoroethyl)benzoyl] 1,3-bis- (D-mannos-4-yloxy)-2-propylamine [( 2-3H] ATB-BMPA) to determine which isoform is activated by protein synthetic blockade. As expected, a 15-fold increase in 2-deoxyglucose uptake in response to insulin was associated with 1.7- and 2.6-fold elevations in plasma membrane GLUT1 and GLUT4 protein levels, respectively. Anisomycin treatment of cultured adipocytes for 5 h produced an 8 fold stimulation of hexose transport but no increase in the content of glucose transporters in the plasma membrane fraction as measured by protein immunoblot analysis. Cell surface GLUT1 levels were also shown to be unaffected on 3T3-L1 adipocytes in response to anisomycin using an independent method, the binding of an antiexofacial GLUT1 antibody to intact cells. In contrast, anisomycin fully mimicked the action of insulin to stimulate (about 4-fold) the radiolabeling of GLUT1 transporters specifically immunoprecipitated from intact 3T3-L1 adipocytes irradiated after incubation with [2-3H] ATB-BMPA. Photolabeling of GLUT4 under these conditions was also significantly enhanced (1.8-fold) by anisomycin treatment, but this effect was only 15% of that caused by insulin. These results suggest that: 1) the photoaffinity reagent [2-3H]ATB-BMPA labels those cell surface glucose transporters present in a catalytically active state rather than total cell surface transporters as assumed previously and 2) inhibition of protein synthesis in 3T3-L1 adipocytes stimulates sugar transport primarily by enhancing the intrinsic catalytic activity of cell surface GLUT1, and to a lesser extent, GLUT4 proteins. PMID- 1310983 TI - Vitamin B6 modulates transcriptional activation by multiple members of the steroid hormone receptor superfamily. AB - Recent studies have shown that vitamin B6 modulates transcriptional activation by the human glucocorticoid receptor in HeLa S3 cells. We have now examined the possibility that vitamin B6 might similarly influence transcriptional activation by the glucocorticoid receptor in other cell types, as well as gene expression mediated by other members of the steroid hormone receptor superfamily. We show that elevated vitamin B6 concentrations suppress by 40-65% the level of transcription mediated through the endogenous murine L cell glucocorticoid receptor, as well as the human receptor transfected into E8.2 and T47D cells. In contrast, glucocorticoid receptor-mediated transcription was enhanced 60-110% in mild vitamin deficiency. The level of hormone-independent constitutive gene expression was not affected by these same alterations in vitamin B6 concentration. These studies indicated that the transcriptional modulatory effects of the vitamin were neither restricted to specific cell types nor limited to the human form of the glucocorticoid receptor. We next determined if hormone induced transcription by several other steroid receptors (androgen, progesterone, and estrogen receptors) was analogously affected by alterations in vitamin B6 concentration. Analysis of gene expression mediated through the mouse mammary tumor virus promoter revealed that transcriptional activation of both the androgen and progesterone receptors was reduced by 35-40% under conditions of elevated vitamin B6 and enhanced by 60-90% in deficiency, again under conditions where constitutive expression was unaffected. Using a different promoter, the estrogen-regulated vitellogenin promoter, we found that transcriptional activation of the estrogen receptor was similarly affected. Estrogen-induced gene expression was reduced by 30% under conditions of elevated intracellular vitamin B6 and enhanced by 85% in vitamin deficiency. Thus, vitamin B6 modulates transcriptional activation by multiple classes of steroid hormone receptors. The similarities in vitamin B6 effects on transcription mediated through different promoters, the mouse mammary tumor virus and vitellogenin promoters, suggest that this vitamin may modulate the expression of a diverse array of hormonally responsive genes. These observations together support the hypothesis that vitamin B6 represents a physiological modulator of steroid hormone action. PMID- 1310984 TI - The glucose transporter of Escherichia coli. Mutants with impaired translocation activity that retain phosphorylation activity. AB - The glucose transporter of the bacterial phosphotransferase system couples translocation with phosphorylation of the substrate in a 1:1 stoichiometry. It is a complex consisting of a transmembrane subunit (IIGlc) and a hydrophilic subunit (IIIGlc). Both subunits are transiently phosphorylated. IIIGlc is phosphorylated at a histidyl residue by the cytoplasmic phosphoryl carrier protein phospho-heat stable phosphoryl carrier protein; IIGlc is phosphorylated at a cysteinyl residue by phospho-IIIGlc. The IIGlc subunit consists of two domains. The N-terminal hydrophobic domain is presumed to span the membrane several times; the C-terminal cytoplasmic domain includes the phosphorylation site. IIGlc phosphorylates glucose and methyl-alpha-D-glucopyranoside in transit across the inner membrane but can also phosphorylate intracellular glucose. Ten mutants resistant against extracellular toxic methyl-alpha-D-glucopyranoside yet capable of phosphorylating intracellular glucose were isolated. Strong impairment of transport activity in these mutants was accompanied by only a slight decrease of phosphorylation activity. Amino acid substitutions occurred at six sites that are clustered in three presumably hydrophilic loops in the transmembrane domain of IIGlc: M17T, M17I, G149S, K150E, S157F, H339Y, and D343G. We presume that the three polypeptide segments are directly involved in sugar translocation and/or binding but are of little importance for phosphorylation activity, folding, and membrane localization of IIGlc. PMID- 1310985 TI - Functional role of heme ligation in cytochrome c. Effects of replacement of methionine 80 with natural and non-natural residues by semisynthesis. AB - The nature of the axial ligation to heme iron has been suggested to be the major determinant of the oxidation-reduction potential of a particular cytochrome, but natural cytochromes that vary significantly in E'm invariably differ from one another in many ways. We proposed to clarify this issue by engineering many different ligation patterns within the same basic molecule, mitochondrial cytochrome c. Since many of the potentially informative substitutions require non coded amino acids, semisynthesis was the approach we chose, and solid-phase peptide synthesis was used to make a set of nin 39-residue peptides that have been incorporated by autocatalytic fragment religation into the structure of horse cytochrome c. An additional two analogues modified at this position were made by chemical modification of the whole protein. As well as looking at the effect on reduction potential, we examined the effect of varying the ligand sphere on the efficiency of the autocatalytic fragment religation reaction, on the conformation of cytochrome c, on its spectroscopic properties, and in promoting electron transfer between heme c and other redox centers. Substitute residues were chosen to put sulfur, selenium, oxygen, and nitrogen, or even no ligating atom at all in the place of methionine sulfur. We found both subtle and dramatic alterations in spectral properties, which were informative about changes in internal structure and stability brought about by the modifications and which may be useful in identifying novel natural ligation patterns. An unexpected finding was that alanine 80 cytochrome c acquires a hemoglobin-like spectrum, and binds O2 most effectively. Reduction potential changes of greater than 300 mV with nitrogen, greater than 400 mV with oxygen, and greater than 300 mV with thiol sulfur ligation were observed, confirming that variation of the ligand sphere is indeed the most effective way in which the protein coat may modulate the potential of the redox center it encloses. Finally, we obtained more evidence that this axial ligand plays an active role in electron transfer and discovered that histidine could be even more effective in this role. PMID- 1310986 TI - Domain structure and interactions of recombinant urokinase-type plasminogen activator. AB - Urokinase-type plasminogen activator (uPA) is a mosaic glycoprotein composed of an epidermal growth factor-like (EGF), a kringle and a serine protease (SP) module. It exists in single and two-chain forms designated HMW pro-uPA and HMW uPA, respectively. A low molecular weight form, LMW uPA, lacks the EGF and kringle modules and is composed of the SP module alone. Recombinant-expressed proteins representing both HMW forms exhibit four reversible unfolding transitions that are resolved by deconvolution of melting curves obtained by differential scanning calorimetry at pH 4.5; no differences in the melting properties of the single and two-chain forms were found. The proteolytic fragment Ser1-Lys135 (EGF-kringle) exhibits two transitions, while the isolated EGF and kringle modules each exhibit a single two-state transition. Thus, both of these modules retain an independently folded compact structure when isolated. The isolated SP module (LMW uPA) exhibits two closely spaced transitions at low pH indicating the melting of two domains of similar stability. Fluorescence-detected melting curves of LMW uPA reveal increasing cooperativity with increasing pH, suggesting an increase in the interaction between the two SP domains. Treatment of both HMW and LMW uPA with the tripeptide inhibitor Glu-Gly-Arg chloromethylketone dramatically increased the stability of both domains of the SP module which now melt together in a single two-state transition, even at low pH, with no effect on the EGF and kringle modules. From these data one concludes that UK consists of four independently folded domains. Two are formed by the EGF and kringle modules which do not interact with each other or with the SP module. The SP module contains two domains that are independent at low pH but exhibit a tendency to merge into a single cooperative unit at neutral pH or after treatment with the tripeptide inhibitor. PMID- 1310987 TI - Genistein differentially inhibits postreceptor effects of insulin in rat adipocytes without inhibiting the insulin receptor kinase. AB - Genistein, an isoflavone putative tyrosine kinase inhibitor, was used to investigate the coupling of insulin receptor tyrosine kinase activation to four metabolic effects of insulin in the isolated rat adipocyte. Genistein inhibited insulin-stimulated glucose oxidation in a concentration-dependent manner with an ID50 of 25 micrograms/ml and complete inhibition at 100 micrograms/ml. Genistein also prevented insulin's (10(-9) M) inhibition of isoproterenol-stimulated lipolysis with an ID50 of 15 micrograms/ml and a complete effect at 50 micrograms/ml. The effect of genistein (25 micrograms/ml) was not reversed by supraphysiological (10(-7) M) insulin levels. In contrast, genistein up to 100 micrograms/ml had no effect on insulin's (10(-9) M) stimulation of either pyruvate dehydrogenase or glycogen synthase activity. We determined whether genistein influenced insulin receptor beta-subunit autophosphorylation or tyrosine kinase substrate phosphorylation either in vivo or in vitro by anti phosphotyrosine immunoblotting. Genistein at 100 micrograms/ml did not inhibit insulin's (10(-7) M) stimulation of insulin receptor tyrosine autophosphorylation or tyrosine phosphorylation of the cellular substrates pp185 and pp60. Also, genistein did not prevent insulin-stimulated autophosphorylation of partially purified human insulin receptors from NIH 3T3/HIR 3.5 cells or the phosphorylation of histones by the activated receptor tyrosine kinase. In control experiments using either NIH 3T3 fibroblasts or partially purified membranes from these cells, genistein did inhibit platelet-derived growth factor's stimulation of its receptor autophosphorylation. These findings indicate the following: (a) Genistein can inhibit certain responses to insulin without blocking insulin's stimulation of its receptor tyrosine autophosphorylation or of the receptor kinase substrate tyrosine phosphorylation. (b) In adipocytes genistein must block the stimulation of glucose oxidation and the antilipolytic effects of insulin at site(s) downstream from the insulin receptor tyrosine kinase. (c) The inhibitory effects of genistein on hormonal signal transduction cannot necessarily be attributed to inhibition of tyrosine kinase activity, unless specifically demonstrated. PMID- 1310988 TI - Inhibition of T cell antigen receptor-dependent phosphorylation of CD4 in human immunodeficiency virus type 1 infected cells. AB - Inhibitory effects of human immunodeficiency virus (HIV) on T lymphocyte function have been linked to perturbation of signaling through the T cell antigen receptor CD3 complex. Comparative biochemical analyses of signaling responses were performed in T cells that were either uninfected or chronically infected with the HIV-1/IIIB strain. Stimulation with antibodies to CD3 triggered both Ca2+ accumulation and phosphoinositide hydrolysis responses that were equivalent in uninfected and infected cells. Treatment with anti-CD3 or with phorbol diester also stimulated serine phosphorylation of CD4 molecules in uninfected T cells. However, phosphorylation of CD4 was not observed after anti-CD3 treatment in HIV infected T cells despite normal phosphorylation responses to phorbol diester. Identical results were obtained using a T cell line that was infected with an env (gp160/120-) HIV-1 defective variant. These studies indicate that infection with HIV-1 inhibits the activation of protein kinase associated with the T cell receptor-CD3 complex by a mechanism which is independent of viral env protein components. PMID- 1310989 TI - Evidence that the hydrophobicity of isolated, in situ, and de novo-synthesized native human placental folate receptors is a function of glycosyl phosphatidylinositol anchoring to membranes. AB - Although normal human chorionic villi-associated hydrophobic placental folate receptors (PFR) are converted to hydrophilic forms by an endogenous, EDTA sensitive, Mg(2+)-dependent protease under serum-free conditions (Verma, R. S., and Antony, A. C. (1991) J. Biol. Chem. 266, 12522-12535), it is not known whether hydrophobic PFR are also susceptible to conversion by endogenous phospholipases. We isolated and characterized hydrophobic PFR, and tested the hypothesis that purified, in situ, and de novo-synthesized native PFR were covalently linked to glycosyl-phosphatidylinositol (GPI) anchors. 125I hydrophobic PFR, but not 125I-hydrophilic PFR, (i) separated into the Triton X 114 micellar phase at 30 degrees C, (ii) efficiently incorporated into phosphatidylcholine-cholesterol liposomes, and (iii) were covalently labeled by the hydrophobic probe 3-(trifluoromethyl)-3-(meta[125I]iodophenyl)diazirine, [125I]TID. (iv) [125I]TID-labeled- and [phenyl-3H]Triton X-100-bound hydrophobic PFR, as well as native PFR in situ, were released as hydrophilic forms by recombinant (r) GPI-specific phospholipase(PL) C (GPI-PLC), and GPI-PLD (but not by PLC), in the absence and presence of a concentration of EDTA known to inhibit endogenous Mg(2+)-dependent protease. (v) Nitrous acid deamination of [125I]TID labeled hydrophobic PFR as well as (r)GPI-PLC cleavage of [phenyl-3H]Triton-X-100 and [125I] TID-labeled hydrophobic PFR, released hydrophobic radiolabeled moieties which comigrated on thin layer chromatography distinct from free radiolabel. Finally, (vi) biosynthetic studies on chorionic villi cultured in vitro revealed incorporation of radiolabeled precursors into the GPI anchor of hydrophobic PFR. We conclude that native hydrophobic PFR are linked to GPI anchors and are therefore potential substrates for three distinct endogenous enzymes (GPI-PLC, GPI-PLD, and specific Mg(2+)-dependent metalloprotease) in maternal serum and placenta in vivo. PMID- 1310990 TI - Processivity of the DNA helicase activity of Escherichia coli recBCD enzyme. AB - A fluorescence assay was used to measure the processivity of Escherichia coli recBCD enzyme helicase activity. Under standard conditions, recBCD enzyme unwinds an average of 30 +/- 3.2 kilobase pairs (kb)/DNA end before dissociating. The average processivity (P obs) of DNA unwinding under these conditions is 0.99997, indicating that the probability of unwinding another base pair is 30,000-fold greater than the probability of dissociating from the double-stranded DNA. The average number of base pairs unwound per binding event (N) is sensitive to both mono- and divalent salt concentration and ranges from 36 kb at 80 mM NaCl to 15 kb at 280 mM NaCl. The processivity of unwinding increases in a hyperbolic manner with increasing ATP concentration, yielding a KN value for ATP of 41 +/- 9 microM and a limiting value of 32 +/- 1.8 kb/end for the number of base pairs unwound. The importance of the processivity of recBCD enzyme helicase activity to the recBCD enzyme-dependent stimulation of recombination at Chi sites observed in vivo is discussed. PMID- 1310991 TI - Purification and localization of brain-type creatine kinase in sodium chloride transporting epithelia of the spiny dogfish, Squalus acanthias. AB - The targeting of creatine kinase isoenzymes to specific sites within muscle cells provides a system for the regeneration of ATP in situ from ADP and creatine phosphate. We have recently reported the colocalization of brain-type (B) creatine kinase and the nonsarcomeric mitochondrial creatine kinase isoenzymes in the thick ascending limb of the loop of Henle in the rat kidney, suggesting that creatine kinase may regenerate ATP for sodium transport (Friedman, D.L., and Perryman, M.B. (1991) J. Biol. Chem. 266, 22404-22410). In order to test the hypothesis regarding the association of B creatine kinase with sodium transport, we examined the creatine kinase enzymes in the rectal (salt-secreting) gland of the dogfish shark which contains high levels of the Na+/K(+)-ATPase. The creatine kinase isoform composition was determined by non-denaturing electrophoresis, immunoblotting, protein purification, and amino acid sequence analysis. The results demonstrate both B creatine kinase and mitochondrial creatine kinase proteins are present in the rectal gland, an isoform composition which is the same as in the mammalian kidney. By using a combination of chromatographic techniques, shark B creatine kinase was purified to homogeneity and partial sequence data was obtained from two cyanogen bromide peptide fragments. One of these fragments contains the active site and is identical at all sequenced residues with the corresponding region from the echinoderm sperm flagellar creatine kinase, and is 96% homologous with both chicken and rat B creatine kinase subunits. The other fragment corresponds to a region near the N-terminal of mammalian creatine kinases and is 89% homologous with B creatine kinase from chicken. The localization of these isoforms was examined by immunocytochemistry using subunit specific antisera. Mitochondrial creatine kinase and B creatine kinase immunoreactivity are detected in all tubules, and is restricted to the basal region of the cells, which is the site of the Na+/K(+)-ATPase. The conservation of creatine kinase isoform expression in excretory tissue, and the localization of creatine kinase immunoreactivity in the basal region of the tubule cells, demonstrate that subcellular compartmentation of B creatine kinase may underly the functional coupling of creatine kinase activity with sodium transport. PMID- 1310992 TI - Cortical localization of a calcium release channel in sea urchin eggs. AB - We have used an antibody against the ryanodine receptor/calcium release channel of skeletal muscle sarcoplasmic reticulum to localize a calcium release channel in sea urchin eggs. The calcium release channel is present in less than 20% of immature oocytes, where it does not demonstrate a specific cytoplasmic localization, while it is confined to the cortex of all mature eggs examined. This is in contrast to the cortical and subcortical localization of calsequestrin in mature and immature eggs. Immunolocalization of the calcium release channel reveals a cortical reticulum or honeycomb staining network that surrounds cortical granules and is associated with the plasma membrane. The network consists of some immunoreactive electron-dense material coating small vesicles and elongate cisternae of the endoplasmic reticulum. The fluorescent reticular staining pattern is lost when egg cortices are treated with agents known to affect sarcoplasmic reticulum calcium release and induce cortical granule exocytosis (ryanodine, calcium, A-23187, and caffeine). An approximately 380-kD protein of sea urchin egg cortices is identified by immunoblot analysis with the ryanodine receptor antibody. These results demonstrate: (a) the presence of a ryanodine-sensitive calcium release channel that is located within the sea urchin egg cortex; (b) an altered calcium release channel staining pattern as a result of treatments that initiate the cortical granule reaction; and (c) a spatial and functional dichotomy of the ER which may be important in serving different roles in the mobilization of calcium at fertilization. PMID- 1310993 TI - Are the conserved sequences in segment 1 of gelsolin important for binding actin? AB - The minimal region required for actin binding in the smallest of the three domains of gelsolin (termed Segment 1 or S1) was previously defined by deletion mutagenesis as residues 37-126. Further analysis of NH2-terminal deletions here redefines the minimal functional core as residues 41-126. Amino acid substitutions within this core further elucidate the nature of the interaction of segment 1 with actin. Of 26 point mutants analyzed, 14 reduced the affinity for actin. The charged residues His 119, Arg 120, Glu 121, and Gln 123 appear to be involved in direct interaction with actin. Substitutions of Leu 108, Leu 112, and Val 117 by polar groups all affect the structural stability of segment 1 and thereby reduce binding affinity. In addition replacement of Glu 126 by aspartic acid modifies the physical properties of segment 1 and weakens binding. We have further shown that changing charged residues within the highly conserved pentapeptide sequence LDDYL (residues 108-112) has no effect on actin binding. This sequence, found in a number of different actin binding proteins, does not therefore constitute part of the interaction site. Similarly, substitution of the two acidic residues by basic ones within the DESG motif of segment 1 (residues 96 99, but also found near the COOH terminus of actin) does not impair binding. These results show the dangers of predicting functional sites on the basis of conserved sequences. PMID- 1310994 TI - In vivo analysis of functional domains from villin and gelsolin. AB - Transfected CV1 cells were used to compare the in vivo effects of various domains of villin and gelsolin. These two homologous actin modulating proteins both contain a duplicated severin-like sequence. Villin has in addition a carboxy terminal domain, the headpiece, which accounts for its bundling activity. The effects of the villin-deleted mutants were compared with those of native villin. Our results show that essential domains of villin required to induce the growth of microvilli and F-actin redistribution are present in the first half of the core and in the headpiece. We also show that the second half of the villin core cannot be exchanged by its homolog in gelsolin. When expressed at high levels of CV1 cells, full length gelsolin completely disrupted stress fibers without change of the cell shape. Addition of the villin headpiece to gelsolin had no effect on the phenotype induced by gelsolin alone. Expression of the first half of gelsolin induced similar modifications as capping proteins and rapid cell mortality; this deleterious effect on the cell structure was also observed when the headpiece was linked to the first half of gelsolin. In cells expressing the second half of gelsolin, a dotted F-actin staining was often seen. Moreover elongated dorsal F actin structures were observed when the headpiece was linked to the second gelsolin domain. These studies illustrate the patent in vivo severing activity of gelsolin as well as the distinct functional properties of villin core in contrast to gelsolin. PMID- 1310995 TI - MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites. AB - The accumulation of two myogenic regulatory proteins, MyoD and myogenin, was investigated by double-immunocytochemistry and correlated with myosin heavy chain expression in different classes of myoblasts in culture and during early myogenesis in vivo. During in vitro differentiation of fetal myoblasts, MyoD positive cells were detected first, followed by the appearance of cells positive for both MyoD and myogenin and finally by the appearance of differentiated myocytes and myotubes expressing myosin heavy chain (MHC). A similar pattern of expression was observed in cultures of embryonic and satellite cells. In contrast, most myogenic cells isolated from newly formed somites, expressed MHC in the absence of detectable levels of myogenin or MyoD. In vivo, the appearance of both myogenin and MyoD proteins was only detected at 10.5 d postcoitum (d.p.c.), when terminally differentiated muscle cells could already be identified in the myotome. Parasagittal sections of the caudal myotomes of 10.5-d-old embryos showed that expression of contractile proteins preceded the expression of myogenin or MyoD and, when coexpressed, MHC and myogenin did not co-localize within all the cells of the myotome. In the limb bud, however, many myogenin (or MyoD) positive/MHC negative cells could be observed in the proximal region at day 11. During further embryonic development the expression of these proteins remained constant in all the muscle anlagens examined, decreasing to a low level during the late fetal period. Western and Northern analysis confirmed that the myogenin protein could only be detected after 10.5 d.p.c. while the corresponding message was clearly present at 9.5 d.p.c., strongly suggesting a posttranscriptional regulation of myogenin during this stage of embryonic development. These data show that the first myogenic cells which appear in the mouse myotome, and can be cultured from it, accumulate muscle structural proteins in their cytoplasm without expressing detectable levels of myogenin protein (although the message is clearly accumulated). Neither MyoD message or protein are detectable in these cells, which may represent a distinct myogenic population whose role in development remains to be established. PMID- 1310997 TI - Reversible adrenocorticotropin deficiency due to probable autoimmune hypophysitis in a woman with postpartum thyroiditis. AB - The natural history and pathogenesis of lymphocytic hypophysitis remain poorly understood. We describe a 34-yr-old woman with postpartum thyroiditis and ACTH deficiency, studied at monthly intervals for 18 months after pregnancy. A significant titer of thyroid peroxidase autoantibodies was detected at 16 weeks gestation, and she was recruited into a prospective study of postpartum thyroid function. Four months postpartum she developed mild hyperthyroidism [free T4 (fT4), 27 pmol/L; TSH, less than 0.2 mU/L] and showed a rise in thyroid peroxidase and thyroglobulin autoantibodies. At 9 months postpartum, serum fT4 and fT3 levels were low normal (8.0 and 1.7 pmol/L, respectively), but TSH was not raised (0.4 mU/L). Subsequent investigation showed a low basal plasma cortisol level (28 nmol/L) in association with undetectable ACTH, and subnormal cortisol responses to depot Synacthen (535 nmol/L at 6 h) and hypoglycemia (peak, 145 nmol/L). FSH, LH, GH, and PRL function and computerized tomography of the pituitary were normal. Retrospective analysis of serum samples taken throughout the postpartum year showed developing hypocortisolemia between 3-9 months postpartum. Each sample was also tested for pituitary autoantibodies using a specific indirect immunofluorescent assay; none was detected. The ACTH deficiency recovered spontaneously, with normal cortisol responses to depot Synacthen (greater than 1380 at 6 h) and hypoglycemia (peak, 590) 14 and 18 months postpartum, respectively. This case illustrates that postpartum pituitary deficiencies are potentially reversible. The pattern of pituitary deficit and postpartum thyroiditis supported a diagnosis of autoimmune hypophysitis. PMID- 1310996 TI - Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. AB - The role of cell surface heparan sulfate in herpes simplex virus (HSV) infection was investigated using CHO cell mutants defective in various aspects of glycosaminoglycan synthesis. Binding of radiolabeled virus to the cells and infection were assessed in mutant and wild-type cells. Virus bound efficiently to wild-type cells and initiated an abortive infection in which immediate-early or alpha viral genes were expressed, despite limited production of late viral proteins and progeny virus. Binding of virus to heparan sulfate-deficient mutant cells was severely impaired and mutant cells were resistant to HSV infection. Intermediate levels of binding and infection were observed for a CHO cell mutant that produced undersulfated heparan sulfate. These results show that heparan sulfate moieties of cell surface proteoglycans serve as receptors for HSV. PMID- 1310998 TI - Immunoglobulins from Graves' patients stimulate phospholipase-A2 in FRTL5 thyroid cells. AB - The well documented ability of immunoglobulins G (IgGs) from Graves' patients to stimulate cAMP production is believed to be involved in the pathophysiology of this disease. It is still under discussion whether other intracellular messengers known to regulate thyroid function might play a similar role. This study shows that phospholipase-A2, a signal pathway unrelated to cAMP, is activated by Graves' IgGs. The IgGs from 67 patients with active Graves' disease, 8 patients with Graves' disease in remission, 5 patients with idiopathic myxedema, 2 patients with Hashimoto's thyroiditis, 57 patients with nonautoimmune thyroid disease, and 65 normal subjects were tested for their ability to stimulate phospholipase-A2 activity, as measured by arachidonic acid release from FRTL5 thyroid cells. The IgGs from patients with active Graves' disease caused a significant increase in arachidonic acid release compared to those from normal subjects, patients with nonautoimmune thyroid diseases, and patients with Graves' disease in remission (P less than 0.0001). The IgGs from active Graves' patients were also able to increase cAMP accumulation in FRTL5 cells. This effect did not correlate with the ability of the same IgGs to induce arachidonic acid release, suggesting that Graves' IgGs stimulate these two pathways by separate mechanisms. Moreover, a subgroup of IgGs that stimulated phospholipase-A2 did not increase the cAMP levels in FRTL5 cells. Our data suggest a novel mechanism of action of Graves' IgGs, the activation of phospholipase-A2, well distinguishable from the known effect on cAMP accumulation. The assay we describe could be helpful in improving the diagnosis and therapy of Graves' disease and in distinguishing it from nonautoimmune thyroid diseases. It also supplies the basis for a prospective subclassification of the Graves' patients, which might become useful to clarify the pathophysiology of this disease. PMID- 1310999 TI - Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency. AB - Fertility was evaluated in 53 female patients with late-onset adrenal hyperplasia (LAH) due to 21-hydroxylase deficiency. The majority of patients (n = 33) were seen for isolated postpubertal hirsutism, 9 patients consulted for sterility, and 11 for irregular menstrual cycles. At the time of diagnosis, the ages of patients ranged from 15-40 yr (mean +/- SD, 24.6 +/- 5.2). No patient had major signs of virilization. The plasma 17-hydroxyprogesterone level was higher than normal in all patients (26.8 +/- 18.9 nmol/L; range, 3.4-139.4) and dramatically increased to 140.1 +/- 80.6 nmol/L (range, 35.2-324.2) after ACTH treatment. Plasma androgen levels were high (testosterone, 3.25 +/- 2.03 nmol/L; delta 4 androstenedione, 13.65 +/- 5.60 nmol/L). Plasma basal and LHRH-stimulated values were normal for FSH and high for LH. Basal and TRH-stimulated plasma PRL levels were normal. Among these 53 LAH patients, only 20 desired a pregnancy. These had a total of 38 pregnancies. Ten patients became pregnant before the diagnosis of LAH and without any treatment; they had a total of 18 pregnancies, 12 of which were successful. Moreover, 19 normal pregnancies without any spontaneous abortion were carried to term by 14 of 16 hydrocortisone-treated patients. One patient needed the association of one cure of clomiphene citrate. Hypofertility in LAH patients seems, therefore, to be relative. Its mechanism is hormonal, with anovulation or dysovulation, due to the continuous steroid feedback of adrenal origin on the hypothalamo-pituitary axis. Hydrocortisone is the appropriate treatment in most cases, reducing adrenal androgen overproduction and relieving hypothalamic-pituitary gonadotropin function, thereby making possible cyclic ovarian activity and ovulations. PMID- 1311000 TI - Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia. AB - Adrenal tumors are being detected more frequently in consequence of the wider application of increasingly sensitive radiological investigation techniques. According to the working hypothesis that more silent adenomas could develop from hyperplastic tissue areas under increased stimulation of the adrenal cortex, heterozygous and homozygous patients with congenital adrenal hyperplasia (CAH) were studied. A high incidence of adrenal masses, nearly 82% in homozygous and 45% in heterozygous patients, was found. There was no correlation between tumor size and serum 17-hydroxyprogesterone concentrations. These tumors are, therefore, probably silent adenomas. On the basis of these results, CAH should always be ruled out in the case of incidentally detected adrenal masses. Since CAH is a relatively frequent disease, and the adrenal carcinoma belongs to the rarest malignant tumors, a malignant transformation of these tumors seems to be unlikely. PMID- 1311001 TI - In situ hybridisation of albumin mRNA in normal liver and hepatocellular carcinoma with a digoxigenin labelled oligonucleotide probe. AB - AIMS: To study the localisation and distribution of albumin mRNA in normal liver and hepatocellular carcinoma by in situ hybridisation with an oligonucleotide probe. METHODS: A 51 base oligonucleotide was synthesised from a sequence at the 5' end of the human albumin gene and the probe was labelled at its 3' end with digoxigenin 11-dUTP. Formalin fixed, wax embedded sections of liver biopsy specimens were used to study the localisation and distribution of albumin mRNA. After in situ hybridisation the bound probe was visualised using a digoxigenin antibody conjugated with alkaline phosphatase. RESULTS: In normal liver albumin mRNA was detected in hepatocytes and no positive signal was observed in biliary epithelium, vascular endothelium, or Kupffer cells. In 75% (9/12) of the hepatocellular carcinomas studied a positive hybridisation signal was observed in tumour cells. CONCLUSIONS: Albumin mRNA can be detected in sections of formalin fixed, wax embedded liver, a digoxigenin labelled probe is ideally suited for in situ hybridisation of liver because there is no background from the detection system. The identification of albumin mRNA may be a useful marker of hepatocellular carcinoma, and the demonstration of albumin mRNA by in situ hybridisation overcomes the potential background problem associated with albumin immunohistochemistry. PMID- 1311003 TI - HPV genotypes in cervical neoplasia in South Africa. PMID- 1311002 TI - Human papillomavirus 16/18 and nasopharyngeal carcinoma. AB - Sixteen cases of nasopharyngeal carcinoma (eight anaplastic and eight well differentiated squamous types) were examined for the presence of human papillomavirus types 16 and 18 genomes using the polymerase chain reaction on paraffin wax embedded biopsy specimens. Although nasopharyngeal carcinoma, particularly the anaplastic type, is strongly associated with Epstein-Barr virus, other factors may be involved in its pathogenesis. No DNA of either human papillomavirus subtype was detected. It is concluded, therefore, that these two "high risk" types of human papillomavirus are not implicated in the pathogenesis of nasopharyngeal carcinoma. The number of cases in this series was small, however, and further studies are warranted using fresh biopsy material and including other viral subtypes. PMID- 1311004 TI - Dendritic sampling across processing streams in monkey striate cortex. AB - Cytochrome oxidase (CO) dense blobs in primate striate cortex provide a striking example of parallel processing of visual information. The level of isolation of the blobs from the surrounding interblob tissue was investigated in the present study by combining CO staining with Golgi impregnation of dendritic arbors in the same tissue sections. The data are based on material from two marmoset and three squirrel monkeys. The analysis was conducted on two types of Golgi preparations. In the first preparation, dense networks of overlapping dendrites were impregnated over blob margins. The results of analyzing these networks with transmission and confocal microscopy revealed that dendritic arbors penetrate freely through blob margins. Statistical analysis revealed that the density of dendritic crossings at blob margins was similar to that found at blob and interblob centers. In the second type of Golgi preparation, single, isolated neurons were impregnated. Studies of such neurons revealed occasional examples of dendritic arbors that appeared to reflect back from blob margins, but counter examples were equally abundant. Bias index analysis indicated that dendritic arbors were generally unaffected by the presence of a nearby blob margin. Scanning a large number of impregnated arbors indicated that at least half of the population of blob-related neurons had dendrites in both blob and interblob territory. Under the conditions of free dendritic penetration of blob margins, the sole factor that determines the level of blob/interblob mixing appears to be the relationship between blob size and the dendritic spread of blob neurons. Interestingly, in both the marmoset and squirrel monkeys this size ratio is similar despite a large difference in their cortical surface area. Thus, it is hypothesized that blob size is optimally matched to the dendritic span so as to create a smooth transition of dendritic sampling from blob to interblob-related processing streams. PMID- 1311005 TI - The effect of local application of 1,25-dihydroxycholecalciferol on osteoclast numbers in orthodontically treated rats. AB - Orthodontic tooth movement requires remodeling of periodontal tissues, especially alveolar bone. 1,25-(OH)2D3, the active form of vitamin D3, is known to be a potent stimulator of osteoclastic bone resorption. The purpose of this study was to investigate the effect of local application of 1,25-(OH)2D3 on osteoclast numbers induced by experimental tooth movement. A piece of orthodontic elastic band was inserted between the first and second upper molars of male Wistar rats weighing about 200 g each. Twenty microL of 1,25-(OH)2D3 (10(-12)-10(-7) mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar. The left side was injected with phosphate-buffered saline (PBS). The number of osteoclasts was counted in a 700 x 1050 microns 2 area of the interradicular septum. The local injection of 1,25-(OH)2D3 caused a dose dependent increase in osteoclast number. The effect of 1,25-(OH)2D3 reached a response plateau at 10(-10) mol/L when greater than a three-fold rise in osteoclast number was attained compared with the PBS-treated controls. While the insertion of a piece of elastic band for three days induced a significant increase in osteoclasts in the alveolar bone, daily injections of 20 microL of 10(-10) mol/M 1,25-(OH)2D3 for three days markedly stimulated the numbers of osteoclasts induced by the insertion of an elastic band. 1,25-(OH)2D3 was apparently synergistic with mechanical stimuli, resulting in enhancement of the numbers of osteoclasts induced by mechanical stimuli alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311006 TI - The role of dental implants in the future. AB - Osseointegration's documented success allowing bone and mucosal tissue to tolerate a titanium implant has dramatically expanded the possibilities of dental care. We can now replace extracted teeth. Maintaining implants is different, but simpler than tooth maintenance. There is much interest in quicker procedures, shorter healing times or other materials to see if they can be as successful as CP titanium. Some may prove to be so. In any case, osseointegration has had as much impact on 20th century dentistry as local anesthetics, fluorides and the air rotor. Our practices and curricula, are changing to remain contemporary and ready for the 21st century. PMID- 1311007 TI - Monocytes from patients with atopic dermatitis are primed for superoxide production. AB - To determine the potential role of monocytes (peripheral blood monocytes, PBMs) in the pathogenesis of atopic dermatitis (AD), we investigated whether PBMs from patients with severe AD are primed to generate toxic oxygen metabolites. To induce in vitro superoxide anion (O2-) production, we used either particulate (e.g., opsonized bacteria or zymosan) or soluble (e.g., phorbol esters) stimuli, which allowed us to test two distinct pathways for reduced nicotinamide-adenine dinucleotide phosphate activation. In addition, PBMs from the same patients were also examined for their levels of expression of the low-affinity receptor for IgE, Fc epsilon receptor 2 (CD23). We found that PBMs, but not peripheral blood neutrophils, from patients with AD were primed for O2- production as compared to PBMs from either normal control subjects or patients with allergic rhinitis. These cells also expressed increased levels of CD23, and there was a significant correlation between these two parameters. Since the monocytes infiltrating into the AD lesions bear CD23, our data suggest that in vivo priming of PBMs and increased O2- production may participate in the pathogenesis of this skin disease. PMID- 1311008 TI - Effects of nedocromil sodium on allergen-induced rhinitis in humans. AB - Sixteen patients with allergic rhinitis were recruited into a double-blind crossover protocol studying the immediate effect of nedocromil sodium (NS) on the pattern of nasal symptoms and secretions after allergen challenge. After pretreatment with placebo or NS, allergen challenge resulted in pruritus, rhinorrhea, nasal congestion, and/or sneezing within 10 minutes in 12 of 16 subjects. Prostaglandin D2 (PGD2), a marker of mast cell degranulation, increased proportionately with symptom scores, remaining above the 95% confidence interval for 120 minutes after both pretreatments. No difference in PGD2 between the NS treatment and placebo-treatment days was observed. Protein markers extravasated through the vasculature (albumin and IgG) or secreted by mucosal glands (lactoferrin) were assayed. Total protein, albumin, IgG, and lactoferrin all remained greater than 95% confidence interval for 100 minutes after allergen challenge in the placebo-pretreated group and 120 minutes in the NS-pretreated group. Although there appeared to be a trend for lower secretion of PGD2, albumin, and IgG in the NS-treated group, the overall differences did not achieve statistical significance. This protocol revealed that two topical 130 microliter doses of a 1% solution of NS failed to significantly reduce allergen-induced symptoms, PGD2 generation, or secretion of albumin, IgG, or lactoferrin when NS was compared with placebo. The anti-inflammatory and mast cell-stabilizing effects of NS may require more prolonged pretreatment before provocation to be effective. PMID- 1311009 TI - High plasma levels of catecholamines during insulin-induced hypoglycemic stress do not cause beta-adrenergic receptor sequestration. AB - In the present investigation insulin-induced hypoglycemia was used as a powerful stimulus to rapidly release epinephrine from the adrenal medulla. Insulin injection raised epinephrine 16-fold and doubled norepinephrine plasma levels. The aim of this attempt was to induce beta-adrenergic receptors (beta-ARs) sequestration in vivo on mononuclear leukocytes (MNLs). The number of total and surface beta-ARs was significantly increased 30 minutes after insulin administration, with only partial recovery at 90 minutes. No detectable receptor sequestration was observed: surface receptors were about 90% of total receptors in all the conditions examined. Isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) accumulation was also increased after 30 minutes (+66%) and 90 minutes (+65%) of insulin injection. Basal and forskolin-stimulated intracellular cAMP values were unchanged. We conclude that, even after a strong release of catecholamines, beta-AR redistribution cannot be demonstrated on MNLs. PMID- 1311010 TI - C-reactive protein inhibits intracellular calcium mobilization and superoxide production by guinea pig alveolar macrophages. AB - C-reactive protein (CRP) is a prototypical acute-phase reactant, the humoral and plasma concentrations of which rise dramatically after tissue injury or inflammation. The effects of CRP on superoxide production and intracellular calcium mobilization by guinea pig alveolar macrophages challenged with platelet activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and phorbol 12-myristate 13-acetate (PMA) were studied. CRP by itself did not activate alveolar macrophages up to a concentration of 100 micrograms/ml, whereas it inhibited superoxide production in a time- and dose-dependent manner with median inhibitory concentration (IC50) values of 4.2 +/- 0.3, 3.0 +/- 0.2, and 3.2 +/- 0.3 micrograms/ml for PAF (10(-7) M), fMLP (10(-7) M), and PMA (10(-9) M), respectively. When CRP was incubated with the agonists before addition to cells, it inhibited PMA-, PAF-, and to a lesser extent fMLP-induced superoxide production. CRP also attenuated the rise in intracellular free calcium levels evoked by fMLP or PAF in a dose-dependent manner. These findings suggest that CRP may play a role in attenuating tissue damage secondary to activation of alveolar macrophages by inhibiting superoxide generation and mobilization of intracellular free calcium. PMID- 1311011 TI - Regulation of phospholipase A2 activation and arachidonic acid metabolism in an interleukin-3-dependent macrophage-like cell line. AB - An interleukin 3 (IL-3)-dependent macrophage-like cell line, 11-1-B3, was newly established from CBA/J mouse bone marrow cell cultures. Assay of eicosanoids in the culture supernatants of the intact and [3H]arachidonic acid (AA)-prelabeled cells showed that, after stimulation with the Ca2+ ionophore A23187, the 11-1-B3 cells synthesized and released relatively large amounts of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) but not LTC4. In addition, 11-1-B3 cells showed Ca(2+)-dependent and alkaline pH-optimal phospholipase A2 (PLA2) activity that preferentially hydrolyzed cleavage of sn-2-arachidonyl- but not sn-2 oleoylphosphatidylcholine. The cellular enzyme was distributed with 90% of the activity in the cytosol and 10% in the membrane fraction. Treatment of cells with A23187 for 5-10 min resulted in five- to sevenfold increases in the membrane associated PLA2 but activity in the cytosol was unchanged. This increase in membrane-associated enzyme activity was transient, returning to the pretreatment distribution after 30 min. In sharp contrast, phorbol myristate acetate (PMA) stimulation failed to induce either eicosanoid release or PLA2 activation, although PMA induced translocation of protein kinase C (PKC) to the membrane fraction within 10 min. The data suggest that increases in cellular Ca2+ directly activate membrane-associated PLA2 and consequently initiate AA metabolism; PKC activation by PMA requires additional steps to activate PLA2, a mechanism that is apparently deficient in the IL-3-dependent M phi-like cells. PMID- 1311012 TI - In vivo latex phagocytosis primes the Kupffer cells and hepatic neutrophils to generate superoxide anion. AB - Activation of liver macrophages during clearance of endotoxins, bacteria, or other particulate materials may be accompanied by the migration of polymorphonuclear neutrophils (PMNs) into the liver and priming of the hepatic phagocytes to release toxic oxygen metabolites. In the present study we investigated the effect of in vivo administration of latex particles on the hepatic sequestration of PMNs and the release of superoxide anion (O2-) by the in situ perfused rat liver and isolated hepatic phagocytes. One hour after an intravenous injection of latex beads, a significant amount of O2- (0.7 nmol/min/g) was produced by the in situ perfused liver. Administration of latex particles into the perfused liver also elicited O2- production. Hepatic phagocytes from latex-treated rats generated large amounts of O2- (2-14 nmol/60 min/10(6) cells) when these cells were stimulated in vitro with opsonized zymosan or phorbol myristate acetate (PMA), whereas phagocytes from saline-treated rats released less than 0.8 nmol O2-. Intravenous infusion of superoxide dismutase or ibuprofen did not prevent the immigration of PMNs to the liver. However, ibuprofen inhibited the production of O2- by the perfused liver. Also, after addition of ibuprofen in vitro to isolated cells, there was more than 50% inhibition of O2- generation by Kupffer cells and hepatic PMNs treated with either zymosan or PMA. These observations suggest that arachidonic acid metabolites play a role in O2- release under these conditions. Thus, activation of the reticuloendothelial system by latex phagocytosis induces the migration of PMNs into the liver and enhances the production of toxic oxygen-derived radicals by these cells and the resident Kupffer cells. The toxic oxygen radicals may also contribute to hepatic injury. PMID- 1311013 TI - Inhibition of neutrophil chemotaxis and chemokinesis associated with a plasma protein in aging rats: selective depression of cell responses mediated by complement-derived chemoattractants. AB - The influence of aging on neutrophil chemotaxis, chemokinesis, and superoxide production was investigated in rats. Animals of two age groups, 3 to 4 months and 20 to 21 months, were used. Equivalent neutrophil chemotactic responses to N formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and bacterial lipopolysaccharide (LPS)-activated plasma were observed in both groups of animals, with cells suspended in Hanks' balanced salt solution (HBSS). However, cross-incubation studies in which cells from young adult rats were exposed to plasma from aged donors, then resuspended in HBSS for testing, showed marked changes in the ability of the cells to respond to the chemoattractants. The response to LPS-activated plasma was reduced, whereas responses to fMLP and LTB4 remained unaltered. Previous incubation of the cells with homologous plasma from young donors produced no effect. The inhibitory activity developing with advancing age affected not only chemotaxis but also random movement stimulated by LPS-activated plasma. The inhibitory activity of chemotaxis and chemokinesis in plasma of aged animals was heat labile (56 degrees C), vanished in the presence of a proteolytic enzyme like trypsin, and was maintained after dialysis with 12,000-Mr retention dialysis tubing. The material did not influence superoxide production by stimulated neutrophils. It is suggested that inhibition of neutrophil locomotion with advancing age is associated with a plasma protein capable of interacting with neutrophil receptors for complement-derived chemoattractants. The inhibitory substance might influence neutrophil responses to infection and inflammation in the elderly. PMID- 1311014 TI - Reactivity of antineutrophil cytoplasmic autoantibodies with mononuclear phagocytes. AB - Antineutrophil cytoplasmic autoantibodies (ANCA) react with proteins found in the granules of neutrophils and the peroxidase-positive lysosomes of monocytes, including myeloperoxidase (MPO), proteinase 3 (PR-3), and elastase. ANCA associated diseases, such as Wegener's granulomatosis and polyarteritis nodosa, are characterized by necrotizing vascular inflammation. The inflammatory lesions typically contain both neutrophils and mononuclear phagocytes, with the latter sometimes predominating, for example, in the granulomatous lesions of Wegener's granulomatosis. We investigated the presence of the ANCA target antigens PR3, MPO, and elastase in mononuclear phagocyte cytoplasm during the course of differentiation in vitro and in alveolar and peritoneal macrophages. We observed that ANCA antigens were down-regulated during mononuclear phagocyte differentiation, with the loss corresponding to that of peroxidase-positive granules. This suggests that ANCA can directly interact only with monocytes and early exudative macrophages and not with mature macrophages. PMID- 1311015 TI - Protein kinase C isoforms in human neutrophil cytoplasts. AB - Granule-poor human neutrophil cytoplasts, prepared without heat or cytochalasin B treatment so as to preserve both motile function and activatable respiratory burst oxidase, were investigated for their content of several isoforms of protein kinase C (PKC). Immunoblotting with isoform-specific rabbit antibodies (Abs) to PKC revealed that both the alpha-specific and the beta(I and II)- specific Abs recognized a protein band of 78 kd comigrating with PKC from rat brain cytosol. The gamma-specific antiserum did not detect any protein of this molecular mass. The cytoplast beta-PKC band was more readily detected than the cytoplast alpha PKC band. Antibodies to beta I- or beta-II- specific PKC sequences showed the beta II subtype to be the predominant form of beta-PKC, although some beta I was also found. The identity of the 78-kd cytoplast bands as PKC was established by the fact that phorbol ester treatment of intact cytoplasts induced translocation of the bands from cytosol to membrane fractions. However, whereas PKC specific activity was similar in cytoplast lysates and brain cytosol, immunoreactivity of cytoplast alpha- and beta-PKC bands was considerably less than that of rat brain. Hydroxylapatite chromatography of partially purified cytoplast PKC revealed two major peaks of PKC activity precisely coeluting with brain alpha- and beta-PKC and displaying comparable enzymatic activities despite the relatively weak immunoreactivity of cytoplast alpha- and beta-PKC. To our knowledge, this is the first demonstration that human neutrophil-derived cytoplasts contain alpha, beta I, and beta II forms of PKC and that each isoform translocates from cytosol to membrane upon exposure to phorbol ester at concentrations that induce superoxide production. In addition, our evidence raises the possibility that cytoplasts may also possess other isoforms of PKC that we are unable to detect with our alpha, beta, and gamma antibodies. Finally, the granule-poor cytoplasts seem a particularly useful preparation in which to examine the role of individual PKC isoforms in neutrophil activation. PMID- 1311016 TI - Role of interleukin 6 (IL-6) in protection from lethal irradiation and in endocrine responses to IL-1 and tumor necrosis factor. AB - Primary responsibility for the induction of various acute phase reactions has been ascribed to interleukin 1 (IL-1), tumor necrosis factor (TNF), or IL-6, suggesting that these cytokines may have many overlapping activities. Thus, it is difficult to identify the cytokine primarily responsible for a particular biologic effect, since IL-1 and TNF stimulate one another, and both IL-1 and TNF stimulate IL-6. In this work, the contribution of IL-6 in radioprotection, induction of adrenocorticotropic hormone (ACTH), and induction of hypoglycemia was assessed by blocking IL-6 activity. Administration of anti-IL-6 antibody to otherwise untreated mice greatly enhanced the incidence of radiation-induced mortality, indicating that like IL-1 and TNF, IL-6 also contributes to innate resistance to radiation. Anti-IL-6 antibody given to IL-1-treated or TNF-treated mice reduced survival from lethal irradiation, demonstrating that IL-6 is also an important mediator of both IL-1- and TNF-induced hemopoietic recovery. A similar IL-1/IL-6 interaction was observed in the case of ACTH induction. Anti-IL-6 antibody blocked the IL-1-induced increase in plasma ACTH, whereas recombinant IL 6 by itself did not induce such an increase. Anti-IL-6 antibody also mitigated TNF-induced hypoglycemia, but did not reverse IL-1-induced hypoglycemia. It is, therefore, likely that TNF and IL-1 differ in their mode of induction of hypoglycemia. Our results suggest that an interaction of IL-6 with IL-1 and TNF is a prerequisite for protection from radiation lethality, and its interaction with IL-1 for induction of ACTH. PMID- 1311017 TI - An endogenous antigenic peptide bypasses the class I antigen presentation defect in RMA-S. AB - The RMA-S cell line was derived from the Raucher virus-induced murine cell line RBL-5 by ethylmethane sulfonate mutagenesis and anti-H-2 antibody plus complement selection (Ljunggren, H.-G., and K. Karre. 1985. J. Exp. Med. 162:1745). RMA-S is defective in the ability to present endogenously synthesized antigens to class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) (Townsend, A., C. Ohlen, J. Bastin, H.-G. Ljunggren, L. Foster, and K. Karre. 1989. Nature [Lond.]. 340:443; Ohlen, C., J. Bastin, H.-G. Ljunggren, L. Foster, E. Wolpert, G. Klein, A. R. M. Townsend, and K. Karre. 1990. J. Immunol. 145:52). This defect has been attributed to the inability of RMA-S to deliver antigenic peptides derived from antigens in the cytosol into the endoplasmic reticulum (ER), where they can associate with class I MHC molecules (Townsend, A., C. Ohlen, J. Bastin, H.-G. Ljunggren, L. Foster, and K. Karre. 1989. Nature [Lond.]. 340:443). We show that RMA-S can present at least one endogenous antigen, vesicular stomatitis virus nucleoprotein (VSV-N), to class I MHC-restricted CTL. RMA-S presents VSV-N to CTL both when infected with VSV or transfected with the VSV nucleoprotein gene. The natural antigenic VSV nucleoprotein peptides purified from either RMA or RMA-S are indistinguishable when analyzed by high performance liquid chromatography. We also show that the genetic defect responsible for the RMA-S phenotype maps to the murine chromosome 17. This chromosome encodes the murine class I MHC genes as well as two genes, HAM-1 and -2, with homology to the adenosine triphosphate-dependent transporter superfamily (Monaco, J. J., S. Cho, and M. Attaya. 1990. Science [Wash. DC]. 250:1723). These results suggest that the system that delivers antigenic peptides from the cytosol to the ER in RMA-S may still be present and retain partial function. PMID- 1311018 TI - Structural analysis of a mouse mammary tumor virus superantigen. AB - It has recently been shown that the minor lymphocyte stimulating-like products expressed by some mice are actually encoded by open reading frames in the 3' long terminal repeats of mouse mammary tumor viruses. These products act as viral superantigens (vSAGs). That is, they stimulate most T cells bearing particular V beta s almost regardless of the rest of the variable components of the T cell receptors expressed by those cells. To find out more about the structure of these vSAGs, a set of truncated vSAG genes was used in transfection and in vitro translation experiments to show that the functional vSAG is a type II integral membrane protein with a large glycosylated extracellular COOH-terminal domain and a small, nonessential, intracellular NH2-terminal cytoplasmic domain. These results are consistent with the fact that the vSAGs must be expressed on the cell surface in order to interact with T cells and class II major histocompatibility complex proteins. They also account for the finding that much of the V beta specificity of the vSAGs is controlled by amino acids at the COOH-terminal end of the vSAG proteins, amino acids that will be extracellular in type II proteins. PMID- 1311019 TI - Inactivation of batrachotoxin-modified Na+ channels in GH3 cells. Characterization and pharmacological modification. AB - Batrachotoxin (BTX)-modified Na+ currents were characterized in GH3 cells with a reversed Na+ gradient under whole-cell voltage clamp conditions. BTX shifts the threshold of Na+ channel activation by approximately 40 mV in the hyperpolarizing direction and nearly eliminates the declining phase of Na+ currents at all voltages, suggesting that Na+ channel inactivation is removed. Paradoxically, the steady-state inactivation (h infinity) of BTX-modified Na+ channels as determined by a two-pulse protocol shows that inactivation is still present and occurs maximally near -70 mV. About 45% of BTX-modified Na+ channels are inactivated at this voltage. The development of inactivation follows a sum of two exponential functions with tau d(fast) = 10 ms and tau d(slow) = 125 ms at -70 mV. Recovery from inactivation can be achieved after hyperpolarizing the membrane to voltages more negative than -120 mV. The time course of recovery is best described by a sum of two exponentials with tau r(fast) = 6.0 ms and tau r(slow) = 240 ms at 170 mV. After reaching a minimum at -70 mV, the h infinity curve of BTX-modified Na+ channels turns upward to reach a constant plateau value of approximately 0.9 at voltages above 0 mV. Evidently, the inactivated, BTX-modified Na+ channels can be forced open at more positive potentials. The reopening kinetics of the inactivated channels follows a single exponential with a time constant of 160 ms at +50 mV. Both chloramine-T (at 0.5 mM) and alpha-scorpion toxin (at 200 nM) diminish the inactivation of BTX-modified Na+ channels. In contrast, benzocaine at 1 mM drastically enhances the inactivation of BTX-modified Na+ channels. The h infinity curve reaches minimum of less than 0.1 at -70 mV, indicating that benzocaine binds preferentially with inactivated, BTX-modified Na+ channels. Together, these results imply that BTX-modified Na+ channels are governed by an inactivation process. PMID- 1311021 TI - Adult polyglucosan body myopathy. AB - This report describes a sporadic late-onset myopathy in two unrelated adults which was marked by polyglucosan inclusions surrounded by abnormally structured mitochondria, the latter finding a localized, possibly reactive phenomenon. The polyglucosan material was characterized by a battery of histochemical and enzyme histochemical techniques; revealed common antigenicity with Lafora bodies, corpora amylacea and muscle fiber inclusions in types IV and VII glycogenoses; and contained ubiquitin. Additional lectin histochemical and associated digestion preparations disclosed the presence of alpha-glycosyl residues as apparently the sole carbohydrate component in polyglucosan bodies while the above mentioned common antigenicity with Lafora bodies and other inclusions suggests an additional, so far unidentified, protein component. PMID- 1311020 TI - Comparison of endogenous and exogenous sources of ATP in fueling Ca2+ uptake in smooth muscle plasma membrane vesicles. AB - A smooth muscle plasma membrane vesicular fraction (PMV) purified for the (Ca2+/Mg2+)-ATPase has endogenous glycolytic enzyme activity. In the presence of glycolytic substrate (fructose 1,6-diphosphate) and cofactors, PMV produced ATP and lactate and supported calcium uptake. The endogenous glycolytic cascade supports calcium uptake independent of bath [ATP]. A 10-fold dilution of PMV, with the resultant 10-fold dilution of glycolytically produced bath [ATP] did not change glycolytically fueled calcium uptake (nanomoles per milligram protein). Furthermore, the calcium uptake fueled by the endogenous glycolytic cascade persisted in the presence of a hexokinase-based ATP trap which eliminated calcium uptake fueled by exogenously added ATP. Thus, it appears that the endogenous glycolytic cascade fuels calcium uptake in PMV via a membrane-associated pool of ATP and not via an exchange of ATP with the bulk solution. To determine whether ATP produced endogenously was utilized preferentially by the calcium pump, the ATP production rates of the endogenous creatine kinase and pyruvate kinase were matched to that of glycolysis and the calcium uptake fueled by the endogenous sources was compared with that fueled by exogenous ATP added at the same rate. The rate of calcium uptake fueled by endogenous sources of ATP was approximately twice that supported by exogenously added ATP, indicating that the calcium pump preferentially utilizes ATP produced by membrane-bound enzymes. PMID- 1311022 TI - Amplification of epidermal growth factor receptor gene in gliomas: histopathology and prognosis. AB - In order to evaluate the incidence and prognostic significance of gene amplification in primary brain neoplasms we measured the number of gene copies per cell of three oncogenes (epidermal growth factor receptor [EGFR] gene, N-myc, C-myc) and syntenic control genes in 40 specimens using quantitative DNA dot blots. We observed EGFR gene amplification in astrocytomas and anaplastic astrocytomas with approximately the same incidence as in glioblastoma multiforme (33%), although large amplifications were only seen in glioblastoma multiforme. Fourteen patients had a supratentorial glioblastoma multiforme; six had EGFR gene amplification and eight had either normal EGFR gene copy number or elevated EGFR copy number attributable to extra copies of chromosome 7. Patients with gene amplification had shorter survival than patients without gene amplification (p = 0.01). The observed difference in survival was not likely to be due to group differences in age, sex, treatment, or histopathology. PMID- 1311023 TI - Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma. AB - PURPOSE: A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS: DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen section immunohistochemical analysis. RESULTS: The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS: EBV-negative, AIDS associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population. PMID- 1311024 TI - Acquired von Willebrand disease in Wilms' tumor patients. AB - PURPOSE: A prospective study was performed to determine the incidence of acquired von Willebrand disease (vWD) in children with newly diagnosed Wilms' tumor. PATIENTS AND METHODS: Fifty consecutive children with newly diagnosed Wilms' tumor were evaluated. Detailed family and bleeding histories were obtained in all cases. Laboratory evaluation included measurement of the circulating platelet count, bleeding time (BT), factor VIII (FVIII) and von Willebrand factor (vWF) levels, and ristocetin cofactor (RCoF) activity. A vWF multimer analysis was obtained in all cases in which vWD was suspected. RESULTS: Four of 50 (8%) consecutive children with a diagnosis of Wilms' tumor were found to have acquired vWD. Laboratory findings indicated type III vWD in two patients and type I vWD in the other two. CONCLUSIONS: The incidence of acquired vWD in association with Wilms' tumor merits further study through a large prospective trial. Such a trial should include careful family and clinical bleeding histories plus measurement of a platelet count, BT, coagulant FVIII and vWF levels, RCoF activity, and vWF multimer analysis. The response to 1-desamino-8-D-arginine vasopressin (DDAVP) should be tested in all patients with Wilms' tumor and acquired vWD, including patients with a type III profile, before an invasive procedure is performed. Successful use of DDAVP may avoid exposure of affected patients to blood products. PMID- 1311025 TI - Competing events determining relapse-free survival in limited small-cell lung carcinoma. The French Cancer Centers' Lung Group. AB - PURPOSE: We report results in terms of relapse-free survival (RFS), obtained in patients with limited small-cell lung carcinoma (SCLC) treated by four consecutive alternating protocols, using a competing risk approach with local recurrences, distant metastases, and death unrelated to cancer as competing events. PATIENTS AND METHODS: Two hundred two patients with limited SCLC were included in four consecutive protocols alternating radiotherapy and chemotherapy (CT). The alternating schedule consisted of six cycles of CT (doxorubicin, etoposide [VP16213], and cyclophosphamide [CAVP16], plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65, and 61 Gy in the four consecutive protocols, respectively (accelerated hyperfractionation was used in the first course of the fourth protocol). A 1-week rest followed each CT cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. RFS variables were determined according to a model assuming competing risks to define the first cause of failure (local disease, distant metastasis, or intercurrent death). RESULTS: No significant differences were observed between the four treatment groups. Overall results showed a 2-year cumulative incidence rate of failure of 75%. When analyzed, the first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. CONCLUSIONS: The methodology of competing risks allowed an unequivocal description of first events in limited SCLC. The extent of the local problem has been relatively overshadowed by the use of conventional descriptive methods. PMID- 1311026 TI - Preradiation intracarotid cisplatin treatment of newly diagnosed anaplastic gliomas. The CNS Cancer Consortium. AB - PURPOSE: This phase II study was performed to assess the response of patients with newly diagnosed, untreated malignant gliomas (anaplastic astrocytoma [AA] and glioblastoma multiforme [GBM]) to intracarotid (IC) cisplatin. PATIENTS AND METHODS: Eligibility criteria included surgical intervention limited to biopsy only, measurable contrast-enhancing tumor, and unilateral tumor location within the vascular territory of one internal carotid artery. Patients were scheduled to receive four infusions of IC cisplatin (75 mg/m2 every 4 weeks) before beginning standard radiotherapy. Twenty-six patients were treated, and 22 were assessable for response. RESULTS: Ten patients (45%) showed a greater than 25% decrease in the enhancing tumor area before radiotherapy with stabilization or improvement of neurologic deficits, and three patients (14%) had a greater than 70% decrease in tumor area. The likelihood of response to IC cisplatin was not clearly linked to patient age, tumor histology, or pretreatment tumor size. Myelosuppression, nephrotoxicity, and ototoxicity were mild. Optic neuropathy occurred in one patient, seizures in two, and fatal postinfusion cerebral edema in one. CONCLUSION: This study design, which permits assessment of the drug sensitivity of the untreated glioma, has shown definite antitumor activity of IC cisplatin in newly diagnosed malignant glioma patients. PMID- 1311027 TI - Identification of patients who are at high risk for locoregional breast cancer recurrence after conservative surgery and radiotherapy: a review article for surgeons, pathologists, and radiation and medical oncologists. AB - PURPOSE: Many retrospective reports have been published identifying risk factors for locoregional (LR) recurrence after breast conservation therapy (BCT). We review these reports, with the purpose of better enabling surgeons, pathologists, radiation oncologists, and medical oncologists to develop strategies for an individualized treatment approach. DESIGN AND RESULTS: English-language retrospective and prospective randomized studies published in the 1980s were reviewed. Histopathologic predictors, young age, extent of conservative surgery (CS), lobular carcinoma, and the impact of adjuvant chemotherapy are all examined as reported risk factors for LR. CONCLUSIONS: Recognition of these factors provides rationale for individualizing the extent of CS based on histopathologic features. In addition, the aggressiveness of radiotherapy (RT) should be dictated by the extent of CS and by identifiable prognostic factors. Strategies are presented for an individualized treatment approach based on a clear understanding of the prognostic factors for LR. PMID- 1311028 TI - Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients. AB - PURPOSE: This review was undertaken (1) to determine the antitumor activity of agents studied in phase II trials in small-cell lung cancer (SCLC) patients, (2) to evaluate the adequacy of published trials, (3) to determine if previously treated patients are suitable for phase II trials in SCLC, and (4) to develop an improved design for phase II trials. DESIGN: English-language, single-agent efficacy trials in SCLC, published from 1970 to 1990, were reviewed. Study design and reporting of results were assessed for clinical and statistical methodology. Response rates observed in previously treated patients were compared with those observed in previously untreated patients. RESULTS: One hundred forty-one articles evaluating 57 agents in 3,042 patients were reviewed. Eleven drugs were active (defined as a response rate greater than or equal to 20% in a trial with greater than or equal to 14 assessable patients), and 12 were inactive. Due to methodologic problems with the clinical trials, the usefulness of the remaining 34 drugs (60%) remains uncertain. Deficiencies identified in trials include inappropriate sample sizes, poorly defined response criteria, and failure to report important prognostic factors. When studied in adequate trials, all agents known to be active in SCLC had an observed response rate greater than or equal to 10% in previously treated patients. CONCLUSIONS: Over the past 2 decades, phase II trials in SCLC have failed in their primary task of effectively identifying agents that warrant further clinical study and rejecting inactive agents. If only previously treated patients had been entered into these trials, no useful agent would have been missed provided that a lower observed response rate had been used as evidence of antitumor activity. We propose a two-stage sequential study design, entering previously treated patients, for future phase II trials in SCLC. PMID- 1311029 TI - Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature. AB - PURPOSE: Hypercalcemia is a rare complication of prostate cancer, and no definite association with any histologic subtype of prostatic malignancy has been documented. We have recently seen three patients who developed hypercalcemia in the setting of prostate cancer. All had neuroendocrine carcinoma of the prostate (NCPs), which prompted an exploration of the potential association of hypercalcemia with NCP. DESIGN: An extensive review of literature published in the English-language was conducted to identify cases of hypercalcemia associated with prostate cancer and well-documented cases of NCP. RESULTS: We found 17 reported cases of hypercalcemia clearly associated with prostate cancer and a total of 61 cases of well-documented NCP. Including our cases, 11 of the 20 reported cases of hypercalcemia associated with prostate carcinoma were in patients with neuroendocrine carcinomas. CONCLUSION: Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies. PMID- 1311030 TI - Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger. AB - White matter of the mammalian CNS suffers irreversible injury when subjected to anoxia/ischemia. However, the mechanisms of anoxic injury in central myelinated tracts are not well understood. Although white matter injury depends on the presence of extracellular Ca2+, the mode of entry of Ca2+ into cells has not been fully characterized. We studied the mechanisms of anoxic injury using the in vitro rat optic nerve, a representative central white matter tract. Functional integrity of the nerves was monitored electrophysiologically by quantitatively measuring the area under the compound action potential, which recovered to 33.5 +/- 9.3% of control after a standard 60 min anoxic insult. Reducing Na+ influx through voltage-gated Na+ channels during anoxia by applying Na+ channel blockers (TTX, saxitoxin) substantially improved recovery; TTX was protective even at concentrations that had little effect on the control compound action potential. Conversely, increasing Na+ channel permeability during anoxia with veratridine resulted in greater injury. Manipulating the transmembrane Na+ gradient at various times before or during anoxia greatly affected the degree of resulting injury; applying zero-Na+ solution (choline or Li+ substituted) before anoxia significantly improved recovery; paradoxically, the same solution applied after the start of anoxia resulted in more injury than control. Thus, ionic conditions that favored reversal of the normal transmembrane Na+ gradient during anoxia promoted injury, suggesting that Ca2+ loading might occur via reverse operation of the Na+)-Ca2+ exchanger. Na(+)-Ca2+ exchanger blockers (bepridil, benzamil, dichlorobenzamil) significantly protected the optic nerve from anoxic injury. Together, these results suggest the following sequence of events leading to anoxic injury in the rat optic nerve: anoxia causes rapid depletion of ATP and membrane depolarization leading to Na+ influx through incompletely inactivated Na+ channels. The resulting rise in the intracellular [Na+], coupled with membrane depolarization, causes damaging levels of Ca2+ to be admitted into the intracellular compartment through reverse operation of the Na(+)-Ca2+ exchanger. These observations emphasize that differences in the pathophysiology of gray and white matter anoxic injury are likely to necessitate multiple strategies for optimal CNS protection. PMID- 1311031 TI - Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using 125I-alpha scorpion toxin. II. Sodium distribution on postsynaptic membranes. AB - A radioiodinated alpha-scorpion toxin (toxin II from Androctonus australis Hector) (alpha ScTx) was used as a probe for EM autoradiography to study the distribution of voltage-dependent sodium channels (Na+ channel) on the postsynaptic side of the mouse neuromuscular junction. Silver grain distribution was analyzed by the cross-fire method to assess the relative Na+ channel density in each membrane domain measured by stereology. This analysis showed that the maximum Na+ channel density was located on the edge of the synaptic gutter, where it reached about twice the mean density in the postsynaptic fold membrane. Na+ channel densities have been calculated using ACh receptor (AChR) density in fold crests as reference. Sodium channel density on the edge of the synaptic gutter was estimated at about 5000/microns 2. Sodium channel distribution in the postsynaptic folds was compared to AChR distribution using density distribution analysis (Fertuck and Salpeter, 1976). The results confirmed that, as already observed by immunogold labeling (Flucher and Daniels, 1989), there are no Na+ channels on fold crests. Na+ channels are located in the rest of the fold membrane (bottom) and may be distributed according to two possible models. In the first, density would be uniformly high, although lower than on the gutter edge. In the second, density would decrease from the crest border, where the value was that of the gutter edge, to the fold end, where the value would be 50% lower. Based on the latter model, which was the "best-fit model," we propose that the postsynaptic membrane includes two domains. The first is the fold crest, which contains almost exclusively AChRs. This domain is devoted to reception transduction of the chemical signal. The second includes both the fold bottom membrane and the perisynaptic membrane. Sodium channel density is highest along the crest border and decreases moving away. Its functions are the integration of postsynaptic potentials and generation-conduction of the muscle action potential. PMID- 1311032 TI - Ca2+ stores in Purkinje neurons: endoplasmic reticulum subcompartments demonstrated by the heterogeneous distribution of the InsP3 receptor, Ca(2+) ATPase, and calsequestrin. AB - The nature of second messenger-responsive intracellular Ca2+ stores in neurons remains open for discussion. Here, we demonstrate the existence in Purkinje cells (PCs) of endoplastic reticulum (ER) subcompartments characterized by an uneven distribution of three proteins involved in Ca2+ storage and release: the inositol 1,4,5-trisphosphate (InsP3) receptor, Ca(2+)-ATPase, and calsequestrin. Ca(2+) ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. Calsequestrin is localized throughout the smooth ER and is particularly concentrated in pleiomorphic vesicles with a moderately electron-dense core, which appear to represent a subcompartment of the smooth ER. In double-labeling experiments many of these vesicles were unlabeled by InsP3 receptor antibodies. These results suggest a key role of the ER as an intracellular Ca2+ store and demonstrate a possible structural basis for distinct intracellular Ca2+ pools regulated by different second messengers. PMID- 1311033 TI - Long-term increases in excitability in the CA1 region of rat hippocampus induced by beta-adrenergic stimulation: possible mediation by cAMP. AB - The cellular mechanisms underlying beta-adrenergic potentiation in the CA1 region of the rat hippocampus were examined. A 10 min treatment with isoproterenol (ISO) induced a long-term depolarization of the pyramidal neurons that persisted for at least 30 min of washout; the ISO-induced decrease in the calcium-activated potassium conductance (afterhyperpolarization, or AHP) was similarly prolonged. The long-term excitability changes induced by ISO did not depend upon the calcium concentration of the medium and could be elicited in medium containing as little as 240 microM calcium. The persistent increase in population spike induced by ISO was mimicked by superfusion with several cAMP analogs and by forskolin (which directly activates adenylate cyclase), but not by the inactive dideoxyforskolin. Forskolin and cAMP analogs also induced decreases in AHPs that could be quite prolonged, but did not depolarize pyramidal neurons as consistently as did ISO. We hypothesize that activation of beta-adrenergic receptors in the CA1 region of hippocampus may induce an alteration of the hippocampal "state" that can persist for as long as several hours, during which the induction of other forms of plasticity may be enhanced. PMID- 1311034 TI - Computer simulations of EPSP-spike (E-S) potentiation in hippocampal CA1 pyramidal cells. AB - Long-term potentiation of hippocampal excitatory synapses is often accompanied by an increase in the probability of spiking to an EPSP of fixed strength (E-S potentiation). We used computer simulations of a CA1 pyramidal neuron to test the plausibility of the hypothesis that E-S potentiation is caused by changes in dendritic excitability. These changes were simulated by adding "hot spots" of noninactivating voltage-sensitive Ca2+ conductance to various dendritic compartments. This typically caused spiking in response to previously subthreshold synaptic inputs. The magnitude of the simulated E-S potentiation depended on the passive electrical properties of the cell, the excitability of the soma, and the relative locations on the dendrites of the synaptic inputs and hot spots. The specificity of the simulated E-S potentiation was quantified by colocalizing the hot spots with a subset (40 of 80) of the synaptic contacts, denoted "tetanized," and then comparing the effects of the hot spots on these and the remaining (untetanized) synaptic contacts. The simulated E-S potentiation tended to be specific to the tetanized input if the untetanized contacts were, on average, electrically closer to the soma than the tetanized contacts. Specificity was also high if the tetanized and untetanized contacts were segregated to different primary dendrites. The results also predict, however, that E-S potentiation by this mechanism will appear to be nonspecific (heterosynaptic) if the synapses of the untetanized input are sufficiently far from the soma relative to the tetanized synapses. Experimental confirmation of this prediction would support the hypothesis that changes in postsynaptic excitability can contribute to hippocampal E-S potentiation. PMID- 1311036 TI - Nuclear medicine and acupuncture message transmission. PMID- 1311035 TI - Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: characterization of tumor and assessment of effect of treatment. AB - To evaluate glucose metabolism in patients with tumors involving the liver, 35 patients with liver lesions had PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG (148 MBq) was injected and radioactivity of the tumor was scanned dynamically by PET. The rate constants (k1, k2, k3, k4) of FDG in a metabolic model were calculated. The results were compared to hexokinase activity in the excised tumor specimens. k3 was found to reflect tumor hexokinase activity. When k3 was used as an index (cut-off value: 0.025), it was possible to distinguish benign and malignant tumors. k4 was significantly higher in hepatocellular carcinoma. By using k3 and k4 as indices, one could assess the degree of differentiation of hepatocellular carcinoma. After treatment, k3 decreased according to the effectiveness of therapy and thus may be a useful index for quantitatively assessing tumor viability. PMID- 1311038 TI - The chemical identity of pentavalent technetium-DMSA and editorial: small coordination complexes in tumor imaging. PMID- 1311037 TI - Membrane trapping of carbon-11-labeled 1,2-diacylglycerols as a basic concept for assessing phosphatidylinositol turnover in neurotransmission process. AB - The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene was developed to label the 1- or 3-hydroxyl group of 2-monoacylglycerol. After intravenous injection, these tracers were metabolized rapidly in the rat brain cortex to phosphatidic acids, phosphatidylinositols and phosphatidylinositol phosphates. The brain cortex anesthetized by barbiturate, which represents inhibited state of synaptic transmission, did not produce differences in uptake values between sn-1,2-[11C]DAG and rac-1,2-[11C]DAG. However, in the liver, lung, and pancreas under the same conditions, the uptake values of rac-1,2-[11C]DAG were higher than those of sn-1,2-[11C] DAG, in which the labeling position was on the 2-hydroxyl group in the sn type. These findings suggest that the lipase activity in the brain should be disregarded because lipase predominantly hydrolyzes the 1- or 3-position of rac-1,2-[11C] DAG, which should be the main factor producing the differences in uptake values in other organs. Cholinergic stimulation prompted accumulation of 1,2-[11C]DAG in the conscious rat brain. In conclusion, sn-1,2-[11C]DAG, administered even in the racemic mixture, could serve as a tracer that becomes mixed with receptor-linked PI turnover and could accumulate in the brain based on the membrane trapping mechanism. PMID- 1311039 TI - Tissue ingrowth into titanium and hydroxyapatite-coated implants during stable and unstable mechanical conditions. AB - Lack of initial mechanical stability of cementless prostheses may be responsible for fibrous tissue fixation of prosthetic components to bone. To study the influence of micromovements on bony ingrowth into titanium alloy (Ti) and hydroxyapatite (HA)-coated implants, a loaded unstable device producing movements of 500 microns during each gait cycle was developed. Mechanically stable implants served as controls. The implants were inserted into the weight-bearing regions of all four femoral condyles in each of seven mature dogs. Histological analysis after 4 weeks of implantation showed a fibrous tissue membrane surrounding both Ti and HA-coated implants subjected to micromovements, whereas variable amounts of bony ingrowth were obtained in mechanically stable implants. The pushout test showed that the shear strength of unstable Ti and HA implants was significantly reduced as compared with the corresponding mechanically stable implants (p less than 0.01). However, shear strength values of unstable HA-coated implants were significantly greater than those of unstable Ti implants (p less than 0.01) and comparable to those of stable Ti implants. The greatest shear strength was obtained with stable HA-coated implants, which was threefold stronger as compared with the stable Ti implants (p less than 0.001). Quantitative determination of bony ingrowth agreed with the mechanical test except for the stronger anchorage of unstable HA implants as compared with unstable Ti implants, where no difference in bony ingrowth was found. Unstable HA-coated implants were surrounded by a fibrous membrane containing islands of fibrocartilage with higher collagen concentration, whereas fibrous connective tissue with lower collagen concentration was predominant around unstable Ti implants. In conclusion, micromovements between bone and implant inhibited bony ingrowth and led to the development of a fibrous membrane. The presence of fibrocartilage and a higher collagen concentration in the fibrous membrane may be responsible for the increased shear strength of unstable HA implants. Mechanically stable implants with HA coating had the strongest anchorage and the greatest amount of bony ingrowth. PMID- 1311041 TI - Neutrophil-mediated damage to human gingival epithelial cells. AB - Polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of inflammatory gingivitis and periodontitis. To further study the role of PMNs in mediating gingival injury, we cocultured these cells in vitro with monolayers of human gingival epithelial cells. Scanning electron microscopy revealed that the epithelial cells were homogeneous and SDS-PAGE/immunoblot analysis identified the presence of keratins K3, K13 and the K6/16 pair which authenticated the oral origin of the cells. Injury to the gingival cells was determined by scanning electron microscopy and measurement of cell detachment and cytolysis. Unstimulated PMNs produced minimal lysis or detachment, but PMNs stimulated by phorbol myristate acetate produced marked epithelial cell detachment without lysis, which was time- and PMN-dose-dependent. Supernatants of activated PMNs were similarly effective, indicating that the mediator was a stable soluble substance. Elastase and cathepsin G, two neutral proteases of PMN origin, produced time- and concentration-dependent detachment of gingival epithelial cells, suggesting that these enzymes may mediate this form of injury. In other studies, gingival epithelial cells were exposed to PMN myeloperoxidase (MPO), chloride and glucose plus glucose oxidase (GO) as a hydrogen peroxide (H2O2) generating system. The toxic oxygen species produced by this system caused lysis of the epithelial targets which was dependent on the duration of incubation and the concentrations of MPO and GO. Azide, an inhibitor of MPO, and catalase, a scavenger of H2O2, inhibited the lytic activity of this system. Scanning electron micrographs of gingival epithelial cells cocultured with activated PMNs showed lifting of the cells from the plating surface, while target cells attacked by the MPO system revealed extensive damage of cell membranes. These studies indicate that activated PMNs cause nonlytic detachment injury to gingival epithelial cells which may be mediated by digestion of their extracellular matrix by granule neutral proteases. Furthermore, PMN MPO is capable of generating toxic oxygen species which can lyse these epithelial cells. Collectively, these actions could have profound adverse effects on the function and integrity of the gingival epithelium. PMID- 1311040 TI - Ultrastructural and ultracytochemical characteristics of multinucleated cells after hydroxyapatite implantation into rat periodontal tissue. AB - Multinucleated cells (MNCs) that appeared after hydroxyapatite (HAP) implantation into experimentally-produced bone defects in rat periodontal tissues were investigated both ultrastructurally and ultracytochemically. At day 5 after implantation, MNCs first appeared along the HAP surface. They had no features of typical osteoclasts such as ruffled border and clear zone. By d 14, these cells acquired features similar to osteoclasts, including ruffled border and clear zone. With the appearance of ruffled borders in MNCs, new bone deposited around the implanted HAP. MNCs appeared to excavate both newly-formed bone and implanted HAP simultaneously. Ingested HAP particles were observed not only in MNCs but also in macrophages. MNCs contained both tartrate-resistant acid phosphatase (ACPase) and carbonic anhydrase (CAase). ACPase activity was detected along all the biosynthesizing pathways in MNCs. Extracellular ACPase activity around the ruffled border region was also demonstrable. CAase activity could be detected only in the cytosol, vesicles and mitochondrial cristae of the MNCs. These cytochemical characteristics were almost the same regardless of the time elapsed after implantation. PMID- 1311042 TI - Cytomegalovirus infection in a cyclosporine-treated burn patient: case report. AB - We report the case of a 45-year-old burned man (55% total body surface area full thickness burn) who developed symptomatic cytomegalovirus infection during cyclosporine (CSA) therapy (3 mg/kg orally) for skin transplantation. During the sixth hospital week the patient developed signs compatible with CMV infection, and CMV was recovered from the urine and sputum. Examination of skin biopsy specimens from the transplanted cadaver allograft revealed inclusion bodies compatible with CMV infection, and CMV antigens were detected by immunohistochemical testing. The CMV infection of the skin was confirmed by recovery of infectious virus and by detection of CMV nucleic acids using in situ hybridization with a biotinylated HCMV DNA probe. Restriction enzyme analysis of a urine CMV isolate and two isolates from skin demonstrated differences in DNA patterns, suggesting that the patient was infected simultaneously with two different CMV strains. PMID- 1311043 TI - Seroprevalence of anti-HCV in an urban child population: a pilot survey in a developing area, Cameroon. AB - Hepatitis C Virus (HCV) is the principal agent of non-A, non-B hepatitis and its spread in the community is not well defined. We evaluated the prevalence of anti HCV (ortho ELISA System) in 696 children (4-14 years) in Kumba, Cameroon. Children were selected by systematic random sampling in six primary schools. A seroprevalence of 14.5% (101 children) was found which increased steadily with age. No significant differences were observed with respect to sex or to family size. There was a highly significant association both with parents' social class, the lowest class presenting a 2.2-fold risk factor, and with area of residence, suburban children showing a significantly higher prevalence (P less than 0.01). These results suggest that Cameroon is endemic for HCV infection, that children are infected at an early age and that infection increases with age. We can therefore hypothesize that transmission of HCV infection in this population is from child to child. Furthermore, the infection seems to be influenced by social factors but not by demographic ones. PMID- 1311044 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1311045 TI - HIV-infected professionals, patient rights, and the 'switching dilemma'. AB - The ethical issues surrounding the Centers for Disease Control and American Medical Association guidelines for health professionals infected with the human immunodeficiency virus are examined and discussed. Although human immunodeficiency virus transmission risks during surgery are lower than many risks we routinely face, it is not irrational for a patient to want to switch from an infected professional to an uninfected one. The American Medical Association claim that physicians have a duty to avoid imposing any identifiable risks is implausible. Knowing the Centers for Disease Control estimate of risks gives us no way to decide whether the rights of patients or those of handicapped (infected) workers should be given priority. Granting priority to patient rights, either by giving patients the opportunity to know the risks they face and to switch to another provider, or by removing infected providers (compulsory switching), makes us all worse off. This gives us reason to reject these guidelines and emphasize other infection control measures. PMID- 1311046 TI - [Polysyndactylia with brachymetacarpia (Type Bonola)]. AB - Four cases of polysyndactyly from Japan, Taiwan and Turkey are described, which show similar short thumbs, metacarpals and middle phalanges as well as analogous malformations of the feet. A new type of polysyndactyly can be defined. The occurrence in brother and sister from a consanguineous marriage is consistent with autosomal recessive inheritance. PMID- 1311047 TI - Superior results of ileoanal pull through (IAPT) in polyposis coli vs ulcerative colitis patients. AB - Colectomy, mucosal proctectomy, and ileoanal pull through (IAPT) have replaced proctocolectomy as the operation of choice in most patients with the colorectal mucosal diseases ulcerative colitis and polyposis coli. This study was conducted to determine whether there is any difference in postoperative morbidity and long term functional results when IAPT is performed for polyposis coli than when it is performed for ulcerative colitis patients. Between 1982 and 1989, 277 IAPT procedures were performed at the University of Utah Medical Center, 239 for ulcerative colitis and 38 for polyposis coli syndromes. A prospective study compared polyposis and colitis patients after IAPT with regards to age, family history, preoperative findings, operative findings, postoperative complications, and long-term complications. Functional results were compared including day and night stool frequency, incidence of nighttime incontinence, and incidence of pouchitis. The incidence of postoperative complications was lower in the polyposis group than in the colitis group, but the numbers were low enough in both diseases that significant differences were not detected. However, the incidence of pouchitis (0% vs 19%), day (4.2 vs 6.0) and night (0.4 vs 0.9) stool frequency, and nighttime incontinence (5% vs 25%) was significantly lower in the polyposis group when compared to the colitis group. We conclude that IAPT performed for polyposis conditions is associated with superior results when compared with results from patients who undergo the procedure for ulcerative colitis. PMID- 1311048 TI - Erythromycin stimulates ileal motility by activation of dihydropyridine-sensitive calcium channels. AB - Erythromycin, a macrolide antibiotic, is a potent stimulant of small bowel motor activity (MA) which may motility either via the peptide motilin receptor or neural mechanisms. We hypothesized that erythromycin stimulates directly stimulates smooth muscle cells by a calcium-mediated event. Thus, we evaluated the effect of neuronal blockade with tetrodotoxin, muscarinic blockade with atropine, and opiate blockade with naloxone on erythromycin-stimulated MA in isolated perfused segments of rabbit terminal ileum. We also tested the effect of nonspecific calcium channel blockade (verapamil and cadmiun) and specific blockade (dihydroxypyridine and nichol) on erythromycin-stimulated MA. MA was measured with a multichannel continuous perfusion manometry catheter. Erythromycin caused a concentration-dependent increase in MA (ED100 5 x 10(-4) M). Tetrodotoxin, atropine, and naloxone did not effect erythromycin-stimulated MA (P greater than 0.05). Both verapamil (10(-7) M) and cadmium (10(-2)-10(-4) M) inhibited erythromycin-stimulated MA. Selective blockade of "l" type calcium channels using dihydropyridine (10(-6) M) and "t" channels with nickel (10(-2) 10(-4) M) both reversed erythromycin-stimulated MA. Since the isolated segments of terminal ileum were free of exogenous humoral and neural effects, these studies indicated that erythromycin directly stimulated MA in the terminal ileum. Furthermore, since tetrodotoxin, atropine, and naloxone did not inhibit this increase in MA, erythromycin acted by a mechanism which was independent of the intrinsic nervous and opiate systems. In conclusion, these data are consistent with the model that erythromycin stimulates ileal motility by a mechanism involving activation of dihydroxypyridine and nickel-sensitive calcium channels. PMID- 1311049 TI - Functional expression of VIP receptors in normal, immortalized and transformed mammary epithelial cells. AB - The effect of VIP and its related peptides on cAMP production has been characterized: 1) in long term culture of normal human mammary epithelial cells (HMEC); 2) in immortalized and transformed ST cell lines established from normal HMEC after genomic insertion of the large T oncogene of SV40; 3) in the spontaneously immortalized HC-11 cells, a clone isolated from the mouse mammary epithelial cells COMMA-1D, described to exhibit normal morphogenesis in vivo and functional differentiation in vitro. Basal cAMP levels were increased 1.5- to 8.7 fold in mammary epithelial cells (p less than 0.001-0.05), with a potency EC50 = 0.02-0.6 nM VIP. The pharmacological specificity of the VIP receptors coupled to cAMP generation was established according to the following potency sequence: VIP greater than PACAP-38 greater than helodermin greater than PHM, PHV greater than helospectin 1 much greater than hpGRF, secretin in HMEC, VIP greater than PACAP 38 greater than helodermin greater than helospectin 1, PHM, PHV greater than hpGRF greater than secretin in S1T3 cells, and VIP, PHI, helodermin greater than PHV greater than rhGRF greater than secretin in HC-11 cells. Our data demonstrate the presence of functional, highly sensitive and specific VIP receptors in normal, immortalized and transformed mammary epithelial cells, suggesting a regulatory role for this neuropeptide on the growth, differentiation and function in normal and neoplastic breast tissue. PMID- 1311050 TI - Neurotensin enhances plasma adrenocorticotropin concentration by stimulating corticotropin-releasing hormone secretion. AB - The systemic administration of neurotensin (NT) dose-dependently increased plasma adrenocorticotropin (ACTH) concentration in rats, and this effect was annulled by (alpha-helical)-CRH9-41, an antagonist of corticotropin-releasing hormone (CRH). The systemic administration of [D-Trp11]-neurotensin (NT-A), a specific NT antagonist, dose-dependently reduced the basal level of circulating ACTH, and this effect was blunted by NT injection. The ACTH inhibitory action of NT-A was completely overcome by the administration of CRH. Taken together, our findings suggest that NT plays a physiologic role in rats, as ACTH secretagogue, and that the mechanism underlying this action of NT involves the stimulation of CRH release. PMID- 1311051 TI - Kinetoplast DNA and molecular karyotypes of Trypanosoma evansi and Trypanosoma equiperdum from China. AB - We compared 12 stocks of Trypanosoma evansi and 1 recently isolated stock of Trypanosoma equiperdum from different regions of China by analysis of kinetoplast DNA (kDNA), nuclear DNA and molecular karyotypes. The T. equiperdum stock was remarkably similar to the T. evansi stocks, except for the possession of kDNA maxi-circles, suggesting a very close evolutionary relationship between T. evansi and T. equiperdum. The maxi-circles of the Chinese T. equiperdum stock were approximately 14.3 kb in size, i.e., about half the size of those of Trypanosoma brucei. This stock is thus similar to an old laboratory stock of T. equiperdum, which also has maxi-circles with a sizeable deletion. Both T. equiperdum and T. evansi kDNA mini-circles hybridised with a T. evansi-specific mini-circle fragment isolated from a Kenyan T. evansi stock. Our results extend the generality that T. evansi and T. equiperdum mini-circles are microheterogeneous rather than homogeneous. Molecular karyotypes obtained by pulsed field gradient gel electrophoresis provided a more sensitive way of distinguishing the T. evansi stocks than isoenzymes or restriction fragment length polymorphisms in kDNA mini circles, genes for ribosomal RNAs and variant surface glycoproteins. Our results fit the general idea that T. evansi stocks worldwide have a single origin. PMID- 1311052 TI - Multiple forms of chromosome I, II and V in a restricted population of Leishmania infantum contrasting with monomorphism in individual strains suggest haploidy or automixy. AB - We have resolved the molecular karyotypes of 22 Leishmania infantum strains isolated between 1980 and 1988 in a restricted geographic area and belonging to zymodemes MON-11, -29 and -33. Three strains were isolated from sandflies and all the others from human cutaneous lesions. A high degree of karyotypic homology is observed among these strains, contrasting with the highly polymorphic MON-1 strains isolated in the same area. We have analysed the time-dependent evolution of size variants of chromosomes I to V, each identified by chromosome-specific DNA probes. More evidence is given for the role of subtelomeric regions in chromosomal size variation in Leishmania for both chromosomes I and II. At the population level, the chromosomes I, II and V are present in respectively 8, 4 and 3 distinct sizes. Furthermore, and despite the small size of the sample, various combinations were observed among these different chromosomal forms. These results could be explained by the occurrence of a high rate of recurrent mutations or of genetic exchange. In contrast, only one chromosomal form was observed in individual karyotypes for the chromosomes I-V. These results could tally with the hypothesis of a haploid organisation for these chromosomes and strains, or, in the frame of a diploid organisation, with the hypothesis of a predominantly automictic sexuality giving rise to 2 identical forms of the homologues in the same strain. PMID- 1311053 TI - The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is encoded by multiple polymorphic tandemly organized genes located on different chromosomes. AB - We demonstrate that cruzipain, the major cysteine proteinase of Trypanosoma cruzi epimastigotes, is encoded by a large number of tandemly arranged genes. Restriction enzyme analysis of 20 clones containing complete repeat units of the gene, as well as sequencing of 2 of these clones, and comparison with previously published partial sequences, indicated that the sequence is conserved among the repeat units, although polymorphisms clearly exist. The repeat units contain an intergenic region of 528 bp and coding regions for pre- and pro-enzyme, a central domain and a C-terminal extension. The predicted amino acid sequences of these regions indicated a sequence identity of 30, 60, 70 and 36%, respectively, when the T. cruzi sequence was compared with the sequence of a similar cysteine proteinase from Trypanosoma brucei. Studies by pulsed field gel electrophoresis, complemented with restriction analysis, indicated that the clusters are located on 2-4 different chromosomes in several parasite isolates. PMID- 1311054 TI - Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation. AB - Cell-fate specification of R7 photoreceptors in the developing Drosophila eye depends on an inductive signal from neighbouring R8 cells. Mutations in three genes, sevenless (sev), bride-of-sevenless (boss) and seven-in-absentia (sina) cause the R7 precursor to become a non-neural cone cell. The sev gene encodes a receptor protein tyrosine kinase (Sev) localized on the R7 surface, activated by a boss-encoded ligand presented by R8. The sina gene encodes a nuclear factor required in R7. Reduction in the dosage of the Ras1 gene impairs Sev-mediated signalling, suggesting that activation of Ras1 may be an important consequence of Sev activation. We report here that Ras1 activation may account for all of the signalling action of Sev; an activated Ras1Va112 protein rescues the normal R7 precursor from transformation into a cone cell in sev and boss null mutants and induces the formation of supernumerary R7 cells. Similar activation of the Drosophila Ras2 protein does not produce these effects, demonstrating Ras protein specificity. PMID- 1311055 TI - Dynamin is a GTPase stimulated to high levels of activity by microtubules. AB - Dynamin was initially identified in calf brain tissue as a protein of relative molecular mass 100,000 which induced nucleotide-sensitive bundling of microtubules. Purified dynamin showed only trace ATPase activity. But in combination with an activating factor removed during the purification, it exhibited microtubule-activated ATPase activity and dynamin-induced bundles showed evidence of ATP-dependent force production. Dynamin is the product of the Drosophila gene shibire, which has been implicated in synaptic vesicle recycling and, more generally, in the budding of endocytic vesicles from the plasma membrane. Dynamin also shows extensive homology with proteins that participate in vacuolar protein sorting and spindle pole-body separation in yeast, and in interferon-induced viral resistance in mammals. All members of this family contain consensus sequence elements consistent with GTP binding near their amino termini, although none has been shown to have GTPase activity. We report here that dynamin is a specific GTPase which can be stimulated to very high levels of activity by microtubules. PMID- 1311056 TI - Crystal structure of a dUTPase. AB - The enzyme dUTPase catalyses the hydrolysis of dUTP and maintains a low intracellular concentration of dUTP so that uracil cannot be incorporated into DNA. dUTPase from Escherichia coli is strictly specific for its dUTP substrate, the active site discriminating between nucleotides with respect to the sugar moiety as well as the pyrimidine base. Here we report the three-dimensional structure of E. coli dUTPase determined by X-ray crystallography at a resolution of 1.9 A. The enzyme is a symmetrical trimer, and of the 152 amino acid residues in the subunit, the first 136 are visible in the crystal structure. The tertiary structure resembles a jelly-roll fold and does not show the 'classical' nucleotide-binding domain. In the quaternary structure there is a complex interaction between the subunits that may be important in catalysis. This possibility is supported by the location of conserved elements in the sequence. PMID- 1311057 TI - [Farmacotherapeutisch Kompas 1992]. PMID- 1311058 TI - [Acyclovir-resistant herpes simplex virus infections in immunocompromised patients]. AB - In order to determine the sensitivity of herpes simplex virus (HSV) isolates from immunocompromised patients treated with antiviral compounds, a retrospective study was carried out in the Clinical Virology Department of the University Medical Centre, Amsterdam. Virus isolates from four AIDS patients and one bone marrow transplant recipient were examined for their sensitivity for the antiviral compounds used by means of plaque reduction assay. In some of the virus isolates, from patients in whom resistance was assumed on clinical grounds, in vitro resistance of the HSV to acyclovir (ACV) could be demonstrated, both after oral and after parenteral administration. There was a clear correlation between the clinical course of the HSV infection and in vitro resistance. ACV resistant virus isolates were sensitive to foscarnet, both clinically and in vitro. In immunocompromised patients treated for some time with ACV for HSV infection, resistance should be considered at lack of results or progression of the lesion and when necessary be demonstrated in vitro. Alternative therapy then consists of intravenous foscarnet treatment. PMID- 1311059 TI - A quick review of neuropathies in A.I.D.S. patients. PMID- 1311060 TI - Activation of the colony-stimulating factor 1 receptor leads to the rapid tyrosine phosphorylation of GTPase-activating protein and activation of cellular p21ras. AB - We have previously reported that platelet-derived growth factor (PDGF) induced tyrosine phosphorylation of GTPase-activating protein (GAP) in intact quiescent fibroblasts under conditions in which insulin and basic fibroblast growth factor (bFGF) were ineffective (Molloy et al., 1988). In the present study, we have provided evidence that colony-stimulating factor 1 (CSF-1) is capable of inducing tyrosine phosphorylation of GAP and its associated cellular proteins, p62 and p190, in NIH3T3 cells overexpressing the human CSF-1 receptor (CSF-1R). However, the extent of GAP tyrosine phosphorylation induced by CSF-1 was approximately 10% of that induced by PDGF-BB in the NIH3T3 fibroblasts. Despite this significant difference, both PDGF-BB and CSF-1 increased the activation of p21ras, the extent of which correlated well with the mitogenic response induced by each growth factor in these cells. Taken together, our findings provide evidence for a possible role of tyrosine phosphorylation of GAP and GAP-associated phosphoproteins in regulating transduction of CSF-1-induced mitogenic signals through p21ras activation. PMID- 1311061 TI - p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. AB - We screened 77 non-small-cell lung cancer (NSCLC) cell lines for mutations of the p53 gene using a single-strand conformation polymorphism (SSCP) assay. We found that 57 cell lines (74%) had mutations of the p53 gene. Three cell lines had a deletion of the p53 gene. Of the remaining 54 cell lines, 49 cell lines were sequenced and 52 mutations were confirmed. In contrast to previously published p53 mutations in other human tumors, the p53 gene mutations in NSCLC were diverse with regard to the location and nature of the mutations. The region corresponding to codons 144-166, which is outside the evolutionarily conserved regions, was a frequent site of p53 gene mutations in NSCLC. The presence of a p53 gene mutation was not associated with age, sex, histological types, culture site, treatment intent, presence of prior cytotoxic treatment, neuroendocrine differentiation, median culture time or patient survival. The prevalence of p53 mutations in cell lines with ras mutations did not differ from that in cell lines without ras mutations. However, p53 gene mutations in NSCLC cell lines with ras mutations tended to cluster in exon 8, suggesting the presence of a functional domain of the p53 gene relating to interaction with the ras gene. We conclude that p53 and ras mutations are frequent and apparently independent genetic alterations which play different roles in the pathogenesis, progression and prognosis of NSCLC. PMID- 1311062 TI - The E5 gene from human papillomavirus type 16 is an oncogene which enhances growth factor-mediated signal transduction to the nucleus. AB - Although human papillomavirus type 16 (HPV-16) is believed to be a major etiological agent in the development of cervical cancer, the biological function of several of its early genes remains to be established. In the present study, we have defined some of the biological properties of the E5 gene from HPV-16. Expression of the HPV-16 E5 gene in 3T3-A31 cells induced transformation to anchorage-independent growth (colony formation in soft agar). Addition of epidermal growth factor (EGF) to the soft-agar medium caused the E5-expressing cells to form larger colonies than those formed in the absence of EGF. Parental 3T3-A31 cells did not form colonies in soft agar either in the presence or in the absence of EGF. Analysis of clones expressing high levels of E5 mRNA revealed that these cells also expressed higher levels of c-fos mRNA in response to serum, EGF and platelet-derived growth factor (PDGF) than did the parental 3T3-A31 cells. Cells expressing the E5 gene were also capable of accelerated growth in low serum and were more tumorigenic in nude mice than were control cells. We conclude that the E5 gene from HPV-16 is an oncogene which transforms cells in part through enhancing signal transduction from growth factors to the nucleus. PMID- 1311063 TI - Human papillomavirus type 16 E5 gene stimulates the transforming activity of the epidermal growth factor receptor. AB - We have until recently made several unsuccessful attempts to assign any activity to the human papillomavirus type 16 (HPV-16) E5 gene product. However, studies with the bovine papilloma virus 1 (BPV-1) E5 protein indicated an interaction with the epidermal growth factor receptor (EGFR). In light of the overall similarity between the HPV and BPV E5 proteins we attempted to determine whether the HPV-16 E5 gene had any common activity. In cells expressing high levels of EGFR plus HPV-16 E5 we found a dramatically increased proliferative activity in soft-agar assays in the presence of EGF. The specificity of this activity was monitored by the addition of other mitogenic agents. The phorbol ester phorbol 12 myristate 13-acetate (PMA) had no effect on the E5-containing cells, although insulin weakly stimulated their growth in soft agar. Further analysis revealed the same number of EGF receptors were present on the E5-containing cells as on the control cells, although the E5 cells were more sensitive to lower concentrations of EGF. These results imply that E5 is amplifying the mitogenic signals from the EGFR in an as yet unknown manner, but which may form the basis of interactions with a variety of growth factor receptors. This report brings to three the number of transforming genes encoded by HPV-16. PMID- 1311064 TI - Expression of genes encoding type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells. AB - Uncontrolled expression of matrix metalloproteinases 2, 3 and 9 (MMP-2, -3 and 9) is believed to be a critical part of the invasive potential of tumor cells because of their ability to degrade type IV collagen, a major structural component of basement membranes. Availability of proteolytic activity in the vicinity of the cell surface is further affected by a local balance between the enzymes and their inhibitors produced by the cell. To determine how frequently deregulated expression of the MMPs and tissue inhibitors of metalloproteinases (TIMPs) is associated with tumor cells, 26 human tumor cell lines were examined by Northern blotting. Transcripts for MMP-2 and MMP-9 were more frequently expressed in mesenchymal tumor cells (9/9 for MMP-2 and 6/9 for MMP-9) than in epithelial tumor cells (4/17 for MMP-2 and 2/17 for MMP-9). Although expression of MMP-2 mRNA was clearly cell type-specific, MMP-9 mRNA expression in mesenchymal cells correlated well with the reported tumorigenicity of the cells. Enhanced expression of MMP-9 mRNA was also associated with the tumorigenic transformation of cells by an activated c-H-ras gene in human embryonic fibroblasts. Only 3 of the 26 tumor cells expressed MMP-3 mRNA, and 2 of the 3 were epithelial tumor cells which coordinately expressed MMP-9 and TIMP-1 mRNAs. TIMP-1 mRNA was almost undetectable in 50% of the tumor cells, but TIMP-2 mRNA was expressed in the majority of the cells. These findings provide comprehensive information about mRNA expression of the MMPs and TIMPs in tumor cells, the deregulation of which is thought to be an integral part of the invasive potential of tumor cells. PMID- 1311065 TI - Inhibition of in vitro myogenic differentiation by a polyomavirus early function. AB - In the present work we report on the role of a polyomavirus (Py) early function in interfering with both morphological and biochemical differentiation of the myogenic C2 cell line. The analysis of cell clones stably transfected with a plasmid carrying an ORI- Py genome showed that in the presence of the whole viral early region myogenesis is blocked and a transformed phenotype is evident. By using a plasmid that only encodes large-T function, the involvement of this individual early viral gene product was determined. Inhibition of myogenic differentiation by Py large T is proportional to the level of its expression. This inhibition does not appear to require alteration of cell growth properties. The analysis of muscle-specific functions expressed at different steps in the myogenic pathway showed that Py large T blocks the expression of terminal differentiation markers without altering the expression of the regulatory gene MyoD. PMID- 1311066 TI - Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. AB - Knowledge of the natural history of symptomatic congenital cytomegalovirus (CMV) infection in the newborn is essential in order to anticipate complications and assess the potential benefit from antiviral therapy. To define the disease course we reviewed data on 106 neonates with symptomatic congenital CMV infection diagnosed and managed by the investigators. Petechiae, jaundice and hepatosplenomegaly were each noted in 70% or more patients. Microcephaly was noted in 54 of 102 (53%) at birth. Elevated alanine aminotransferase, conjugated hyperbilirubinemia and thrombocytopenia were seen in 83, 81 and 77%, respectively. Eighty-six percent had at least two of the manifestations highly suggestive of congenital infection. Platelet count fell to its nadir during the second week of life whereas elevated alanine aminotransferase and direct bilirubin persisted past the first month. In spite of the difficulty in assessing central nervous system function in the newborn, evidence of damage was present in the majority. Seventy-two had microcephaly, poor suck, lethargy/hypotonia or seizures. Abnormal computerized tomographic scan was present in 16 of 20 (80%) and decreased hearing in 20 of 39 (56%). Cerebrospinal fluid protein was greater than 120 mg/dl in 24 of 52 (46%) and this elevation was associated with neurologic abnormalities as well as hearing loss. The mean length of hospital stay was 13 and 22.4 days for term and preterm infants, relatively. Thirteen infants (12%) died during the first 6 weeks of life. Disseminated CMV infection with multiorgan involvement was evident in 7 of 9 at postmortem examination. We conclude that neonates with symptomatic congenital CMV infection have a multi system disease with significant morbidity and mortality. PMID- 1311067 TI - Prophylactic oral acyclovir in outbreaks of primary herpes simplex virus type 1 infection in a closed community. AB - Oral acyclovir was given prophylactically to 37 children in the early stages of three outbreaks of herpes simplex virus type 1 (HSV-1) infection and the results were compared with those in untreated control subjects in two other outbreaks. The rates of seroconversion to HSV were significantly reduced in children treated with acyclovir compared with control subjects (91% vs 27%, P less than .001). The incidence of symptomatic disease was also significantly reduced (82% vs 0%, P less than .001). In some children receiving prophylactic acyclovir, anti-HSV antibody titers did not rise despite the presence of replicative HSV on throat swabs just before the start of treatment. Restriction endonuclease analysis of isolated HSV-DNA confirmed that one strain was responsible for the five outbreaks. No resistance to acyclovir was detected during the study, and no adverse effects of treatment were noted. In conclusion, short-term prophylactic acyclovir may limit the spread and reduce clinical manifestations of HSV infections in closed communities, although this use should be restricted to communities where severe symptoms are observed. PMID- 1311068 TI - Optimal tRNA((Ser)Sec) gene activity requires an upstream SPH motif. AB - The X. laevis tRNA((Ser)Sec) gene is different from the other tRNA genes in that its promoter contains two external elements, a PSE and a TATA box functionally equivalent to those of the U6 snRNA gene. Of the two internal promoters governing classical tRNA gene transcription, only subsists the internal B box. In this report, we show that the tRNA((Ser)Sec) contains in addition an activator element (AE) which we have mapped by extensive mutagenesis. Activation is only dependent on a 15 bp fragment residing between -209 and -195 and containing an SPH motif. In vitro, this element forms a complex with a nuclear protein which is different from the TEF-1 transcriptional activator that binds the SV40 Sph motifs. This AE is versatile since it shows capacity of activating a variety of genes in vivo, including U1 and U6 snRNAs and HSV thymidine kinase. Unexpectedly for an snRNA related gene, the tRNA((Ser)Sec) is deprived of octamer or octamer-like motifs. The X.laevis tRNA((Ser)Sec) gene represents the first example of a Pol III snRNA type gene whose activation of transcription is completely octamer-independent. PMID- 1311069 TI - Sequence specificity of cyclobutane pyrimidine dimers in DNA treated with solar (ultraviolet B) radiation. AB - Cyclobutane pyrimidine dimers were quantified at the sequence level after irradiation with solar ultraviolet (UVB) and nonsolar ultraviolet (UVC) light sources. The yield of photoproducts at specific sites was dependent on the nucleotide composition in and around the potential lesion as well as on the wavelength of ultraviolet light used to induce the damage. Induction was greater in the presence of 5' flanking pyrimidines than purines; 5' guanine inhibited induction more than adenine. UVB irradiation increased the induction of cyclobutane dimers containing cytosine relative to thymine homodimers. At the single UVC and UVB fluences used, the ratio of thymine homodimers (T mean value of T) to dimers containing cytosine (C mean value of T, T mean value of C, C mean value of C) was greater after UVC compared to UVB irradiation. PMID- 1311070 TI - During negative regulation of the human papillomavirus-16 E6 promoter, the viral E2 protein can displace Sp1 from a proximal promoter element. AB - The principal early promoter of human papillomaviruses (HPVs), designated P97 in the case of HPV-16, contains four characteristically aligned cis-responsive elements, namely one binding site for Sp1, two for the viral E2 proteins, and the TATA box. The Sp1 binding site is needed to mediate activation of P97 by the remote epithelial-specific enhancer, and the two E2 binding sites contribute to a negative feedback-loop of viral gene expression. The Sp1 consensus motif and the TATA-box distal E2 binding site are spaced in all genital papillomaviruses by a single nucleotide. We show here that at physiological concentrations, the binding of E2 proteins and Sp1 are mutually exclusive events, since a bandshift analysis with nuclear extracts from ID13, a mouse cell line transformed by BPV-1, showed only the E2 or the Sp1 bandshift, but no complex indicative of the concomitant binding of both factors. Increasing concentrations of in vitro translated E2 protein compete efficiently with the Sp1 factor for binding to an oligonucleotide containing both binding sites. Interference between Sp1 and E2 protein binding is apparently relevant for P97 repression in vivo, since a mutational analysis revealed that both E2 binding sites are necessary for negative transcriptional regulation: Alone, neither the distal site, where E2 protein can induce Sp1 displacement, nor the proximal site, where E2 protein interferes with formation and function of the pre-initiation complex, have a significant effect, but two functional E2 binding sites lead to repression of P97. PMID- 1311072 TI - Complete nucleotide sequence of a highly infectious avian leukosis virus. PMID- 1311071 TI - The transcriptionally-active MMTV promoter is depleted of histone H1. AB - We have used an ultraviolet light cross-linking and immunoadsorption assay to demonstrate that histones H1 and H2B are bound to the repressed MMTV promoter. Hormone activation results in reduced H1 content with little or no change in H2B. High resolution analysis of the glucocorticoid-inducible DNaseI hypersensitive region demonstrates an NF-1 footprint as well as specific sites of enhanced cleavage on nucleosome B and in the nucleosome B/nucleosome A linker. These results are consistent with a model in which binding of the glucocorticoid receptor to glucocorticoid regulatory elements on the surface of nucleosome B induces a chromatin transition that is necessary for transcription factor (NF-1 and TFIID) recruitment to the MMTV promoter. We hypothesize that association of histone H1 with important cis-elements on the promoter masks these sites, and glucocorticoid-induced displacement of H1 is necessary to expose factor binding sites at the 3' edge of nucleosome B, in the nucleosome B/nucleosome A linker and at the 5' edge of nucleosome A. PMID- 1311073 TI - A general and fast method to generate multiple site directed mutations. PMID- 1311074 TI - Identification of a complete P-element in the genome of Drosophila bifasciata. AB - A full-size P-element (IbifM3) was isolated from a genomic library of Drosophila bifasciata. The sequence has a length of 2935 bp and is flanked by 8 bp duplications of the target site. The termini are formed by 31 bp inverted repeats. The four exons have intact reading frames and possess the coding capacity for a protein of 753 amino acids and a molecular weight of 86.4 kd. The sections of the D. melanogaster transposase presumed to be functionally important (three leucine zippers and a helix turn helix motif) are conserved in the D. bifasciata P-element. Copy number and genomic distribution resemble the situation in true P-strains of D. melanogaster. Both findings support the idea that IbifM3 represents an active transposon. The sequence comparison between the P-elements of D. bifasciata, D. melanogaster and Scaptomyza pallida reveals relationships not in accordance with the phylogeny of the species. This result suggests a further case of horizontal transmission involving mobile elements in the genus Drosophila. PMID- 1311075 TI - The recognition of DNA cleavage sites by porcine spleen topoisomerase II. AB - The cutting sites specificity of topoisomerase II from porcine spleen were determined by a modified Sanger's DNA sequencing method. The topoisomerase II prefers to cut DNA at the 3' side of A and leave 5' protruding end with two staggering bases. Through the free energy analysis for DNA duplex, we also found that the topoisomerase II seemed cut DNA preferably at energetically unstable regions. So it is concluded that the specific DNA cutting by porcine spleen topoisomerase II has two structural recognition factors: one is to localize around the energetically unstable region and another is to act at the 3' side of A base. PMID- 1311076 TI - Directional recombination is initiated at a double strand break in human nuclear extracts. AB - The involvement of a double strand break in the initiation of homologous recombination was examined in human nuclear extracts. M13 duplex derivatives, containing inserts in the LacZ' region (producing white plaques), were cleaved by restriction enzymes and coincubated in the extracts with a circular plasmid containing the LacZ' region without insert, and unable to produce plaques. Repair was estimated by the ability to produce plaques after transfection into JM109 (recA1) bacteria. Recombination with the plasmid enhances the number of plaques and also the frequency of M13 producing blue plaques. Heterologous insertions in the region surrounding the break were analyzed for their effects on initiation of recombination. The extent of repair by recombination (number of plaques) was compared with the number of blue plaques among the repaired population. Initiation of recombination is inhibited when heterologous insertions are located at 7bp from the break, on the right side as well as on the left side. A low level of recombination is measurable for 27 bp of homology but the maximum efficiency of recombination occurred with homologies of 165 or 320 bp from the break to the heterologous insertion. At 320 bp, the extent of recombinational repair remained at a plateau level but the frequency of blue plaques progressively decreases. We have also analyzed the effect of different sizes of inserts. With longer inserts, a longer length of homology adjacent to the break is required for optimum recombination. However, the size of the insert does not affect the low level of recombination that occurred with a short homology (27 bp). The results indicate that the process is initiated at or near the break, requires homology on both sides of the break and is followed by an elongation from the double strand break to the distal regions of the DNA. Our data provide some support to the double strand-break repair model established for meiotic recombination in yeast. PMID- 1311078 TI - Estimation of the proportions of mutant and normal N-ras alleles by allele specific restriction analysis. PMID- 1311077 TI - Transcriptional enhancer related DNA sequences: anomalous 1H NMR NOE crosspeaks. AB - A dynamic heterogeneity which correlates with the function of the operator DNA in the lactose operon of E. coli. was previously observed (1) as a local minimum in the thymine imino proton T1 centered at a GTG/C-CAC sequence. Since this triplet occurs frequently in DNA regulatory regions, it was proposed that these sequences may be part of a structural element for specific protein interaction. We examine here three additional biologically significant 17 base pair duplexes containing GTG/CAC triplets: (1) a sequence from the mouse heavy chain immunoglobulin enhancer, (2) a sequence from the critical core of the Simian Virus 40 (SV40) enhancer, and (3) a sequence from pBR322 plasmid used as control for experiments with the SV40 DNA sequences. The 1H NMR resonance assignment for nearly all the nonexchangeable protons for both eukaryotic enhancer duplexes with the exception of the H5'/H5" protons was accomplished to use for structural analysis of these duplexes. The data presented show several NOE's associated with the GTG/CAC triplets which suggest structural variation from uniform B-DNA. In addition, anomalous broad crosspeaks for the fixed thymine methyl to its own H6 proton in combination with the imino proton kinetics associated with these triplets reinforces the original observation of a sequence dependent dynamic variation. PMID- 1311079 TI - A PCR method for introducing mutations into cloned DNA by joining an internal primer to a tagged flanking primer. PMID- 1311080 TI - [Treatment of venous thrombosis with low molecular weight heparin and fluindione]. AB - Thirty-one consecutive patients with deep vein thrombosis were treated with Fraxiparine, a low molecular weight heparin, and fluindione, an oral anticoagulant prescribed at an early stage. Despite the weight/biological effectiveness ratio, the dose of Fraxiparine had to be adjusted in 46 percent of the patients to remain within the therapeutic range selected (0.5 to 1 antiXa/ml units). The early administration of fluindione reduced the duration of heparin therapy to 5.75 days. Using a prescription guide on days 2 and 4 might improve the safety of the fluindione induction. PMID- 1311081 TI - Characterization of a guanine nucleotide-releasing factor and a GTPase-activating protein that are specific for the ras-related protein p25rab3A. AB - The rab3A gene product is a 25-kilodalton guanine nucleotide-binding protein that is expressed at high levels in neural tissue and has about 30% homology to the ras gene product. Recombinant Rab3A protein and p25rab3A purified from bovine brain membranes have been used as substrates to look for factors that regulate its biochemical activity. A factor in rat brain cytosol exists that accelerates, by approximately 10-fold, the release and subsequent rebinding of guanine nucleotides to both native and recombinant p25rab3A. We have partially purified this activity, termed Rab3A-GRF, and a GTPase-activating protein (Rab3A-GAP) reported previously. The two activities copurified through a variety of procedures but were separated by Mono Q anion-exchange chromatography, indicating that the activities arise from distinct polypeptides. Both factors were thermolabile, sensitive to trypsin, and specific for Rab3A, exhibiting little or no activity toward c-Ha-Ras or Rab2 proteins. By gel filtration chromatography and sucrose density ultracentrifugation, both Rab3A-GRF and Rab3A-GAP have Stokes radii of 79 A and sedimentation coefficients of 8.9 S. We calculate a molecular mass of 295,000 daltons and a frictional ratio of 1.80 for each factor. PMID- 1311082 TI - Nonconventional opioid binding sites mediate growth inhibitory effects of methadone on human lung cancer cells. AB - Methadone was found to significantly inhibit the in vitro and in vivo growth of human lung cancer cells. The in vitro growth inhibition (occurring at 1-100 nM methadone) was associated with changes in cell morphology and viability detectable within 1 hr and was irreversible after a 24-hr exposure to the drug. These effects of methadone could be reversed in the first 6 hr by naltrexone, actinomycin D, and cycloheximide, suggesting involvement of opioid-like receptors and the requirement for de novo mRNA and protein synthesis. The inhibitory effects of methadone on the growth of lung cancer cells also could be achieved by the less addictive (+) isomer of methadone. Characterization of the methadone binding to lung cancer cell membranes revealed high-affinity (nM), saturable binding sites for (+/-)-[3H]methadone, which cross-reacted with ligands for kappa, phencyclidine, sigma, but not mu, and delta opioid receptors, and the binding characteristics appeared to be different from methadone sites present in rat brain. Methadone decreases cAMP levels in lung cancer cells, but the receptors are not coupled to a pertussis toxin-sensitive guanine nucleotide binding regulatory protein. We conclude that the lung cancer growth inhibitory effects of methadone are significant, occur at low concentrations, and are mediated by a nonconventional type of opioid binding site distinct from methadone receptors found in the brain. PMID- 1311083 TI - Synthesis of receptor antagonists of neuropeptide Y. AB - We report the synthesis of receptor antagonists of neuropeptide Y (NPY) by a strategy based on synthesis of mixtures of analogs and the subsequent isolation and identification of receptor antagonists from these mixtures. After screening a series of mixtures of NPY analogs by using an NPY antagonist assay, two potent receptor antagonists, designated PYX-1 and PYX-2, were isolated from an antagonist-containing mixture. Structural analysis revealed these analogs to be Ac-[3-(2,6-dichlorobenzyl)Tyr27, D-Thr32]NPY-(27-36) amide and Ac-[3-(2,6 dichlorobenzyl)Tyr27,36,D-Thr32]NPY-(27-36) amide, respectively. The receptor antagonists inhibited release of intracellular calcium elicited by NPY in human erythroleukemia cells and displaced 3H-labeled NPY from NPY receptors in rat brain membrane. The approach of screening and identifying useful analogs from synthetic mixtures may significantly reduce the time and resources previously required for development of receptor antagonists. PMID- 1311084 TI - Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor. AB - The murine Pax-2 gene contains a protein coding domain homologous to the Drosophila paired-box, first described in certain developmental control genes of the segmentation type. Polyclonal antibodies recognize two Pax-2 proteins that are encoded by differentially spliced mRNAs. The Pax-2 proteins can bind a DNA sequence known to interact with the paired domain of a Drosophila protein. By immunocytochemistry, expression of Pax-2 could be localized to the nuclei of condensing mesenchyme cells and their epithelial derivatives in the developing kidney. Expression is abruptly down-regulated as the tubular epithelium differentiates. High levels of Pax-2 expression could also be detected in the epithelial cells of human Wilms tumors. These data suggest that Pax-2 is a transcription factor active during the mesenchyme-to-epithelium transition in early kidney development and in Wilms tumor. PMID- 1311085 TI - Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. AB - Expression of the viral oncogene encoding the simian virus 40 (SV40) large tumor antigen (T antigen) typically promotes tumorigenesis in mammalian cells. To generate transgenic mice that express T antigen in rod photoreceptors, a chimeric construct consisting of a mouse opsin promoter fragment fused to the coding region of SV40 T antigen was generated. Expression of T antigen in the transgenic retina began at early stages of postnatal development concomitant with expression of endogenous opsin. Instead of inducing hyperplasia or tumor formation, T antigen expression caused a rapidly progressing photoreceptor degeneration. The degeneration was accompanied by sustained DNA synthesis in photoreceptor cells, as evidenced by incorporation of [3H]thymidine and by the appearance of mitotic figures at postnatal day 10, a stage when nontransgenic photoreceptor cells are postmitotic and quiescent. Although transgenic photoreceptor cells undergo S phase and enter mitosis, the consequences of T-antigen expression are not proliferation and tumorigenesis but proliferation and cell death. PMID- 1311086 TI - Association of the halobacterial 7S RNA to the polysome correlates with expression of the membrane protein bacterioopsin. AB - The sedimentation behavior of the halobacterial 7S RNA and bacterioopsin mRNA was assessed after application of total cell lysates to sucrose gradients. These two RNAs cosedimented predominantly with membrane-bound polysomes, and the quantity of 7S RNA bound to the ribosomes was directly correlated with the expression of bacterioopsin. Puromycin treatment released the 7S RNA from the polysomes, indicating that it is transiently associated with protein translation. We suggest that halobacteria contain a signal-recognition-like particle involved in translation of membrane-associated proteins. PMID- 1311087 TI - A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains. AB - Retinoic acid receptors are ligand-dependent transcription factors that stimulate gene transcription from promoters containing retinoic acid or thyroid hormone response elements. We describe a high-affinity binding site from the rat oxytocin promoter that mediates negative transcriptional regulation by the retinoic acid receptor. To examine whether strong, constitutive transactivation domains would be capable of stimulating gene transcription when bound to this DNA binding site that normally mediates transcriptional repression, we fused the transactivation domain of the herpes simplex viral protein VP16 to the amino terminus of the retinoic acid receptor and tested the activity of the chimeric protein on the negative retinoic acid response element. This chimeric retinoic acid receptor acted as a strong, constitutive transactivator when bound to promoters containing palindromic thyroid hormone/retinoic acid response elements but surprisingly it still repressed gene transcription when bound to promoters containing the oxytocin-negative retinoic acid response element. These results suggest that a negative DNA binding site itself can inhibit the function of even potent constitutive transactivation domains, and provide evidence that tethering of a constitutive transactivation domain to DNA is insufficient to activate gene transcription. PMID- 1311088 TI - Immortalization of primary human smooth muscle cells. AB - Primary human aortic and myometrial smooth muscle cells (SMCs) were immortalized using an amphotropic recombinant retroviral construct containing the E6 and E7 open reading frames (ORFs) of human papillomavirus type 16. The SMCs expressing the E6/E7 ORFs have considerably elevated growth rates when compared with nonimmortalized control cells and show no signs of senescence with long-term passage. The first SMC line derived in this study has been maintained in continuous tissue culture for greater than 1 year (greater than 180 population doublings). The immortalized SMCs have decreased cell size and decreased content of muscle-specific alpha-actin filaments as determined by indirect immunofluorescence. Southern blot analysis has demonstrated the stable integration of the E6/E7 ORFs in the retrovirally infected cells, and radioimmunoprecipitation has confirmed the continued expression of the E6 and E7 genes. Cytogenetic studies of the SMC lines have revealed essentially diploid populations except for the myometrial clonal line, which became aneuploid at late passage (greater than 125 doublings). These cell lines were not tumorigenic in nude mice. PMID- 1311089 TI - IS5: a mobile enhancer of transcription in Escherichia coli. AB - The cryptic bgl operon of Escherichia coli is activated by the spontaneous insertion of mobile DNA elements. Screening of a collection of such mutations revealed insertion of the 1195-base-pair element IS5 into various positions both upstream and downstream of the bgl promoter P0. Activation of the operon was in all cases attributable to enhancement of P0 activity. Introduction of internal deletions into IS5 almost completely abolished P0 enhancement, demonstrating that enhancement is not simply the result of mutational inactivation of some inhibitory sequences. Intact copies of IS5 in trans restored the enhancing activity of the deletion derivatives. The trans-activator is encoded by IS5 gene ins5A, an essential transposition function. Activation of gene expression by means of interaction of a defective mobile element in cis with functions encoded by a nondefective element in trans has so far been described only for a maize controlling element. PMID- 1311090 TI - A strategy for the generation of conditional mutations by protein destabilization. AB - Conditional mutations such as temperature-sensitive (ts) mutations are important for the analysis of protein function but are often difficult, or impossible, to obtain. Here we present a simple method for generating conditional mutations based on the use of a protein-destabilizing genetic element in combination with systems allowing the induction and repression of gene expression. This genetic cassette can be fused to other protein-coding sequences, and once transcription is turned off and synthesis of the gene product ceases, the preexisting protein is rapidly degraded. We have applied this method to the analysis of the yeast ARD1 gene product, a subunit of an N-terminal acetyltransferase, and show that a complete loss of ARD1 product can be achieved in less than one generation. Despite the rapid loss of ARD1 protein, there is a prolonged delay in the expression of the ard1 mutant phenotype, suggesting that the acetylated substrates of ARD1 are metabolically stable and/or exert a long-lasting effect on processes such as the repression of the silent mating type cassettes. PMID- 1311091 TI - Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice. AB - We have used PCR to study the expression of T-cell antigen receptor beta RNA containing particular variable region (V) elements from transcripts directly in the cells isolated from joints and lymph nodes of B10.Q mice (H-2q) immunized with chicken type II collagen. Our data show that the T cells present in arthritic joints expressed only a few V beta transcripts--V beta 2, -6, -7, -8.2, -9, -10, and -15. V beta 6 and -8.2 were expressed predominantly (six out of seven animals) while others were expressed at a relatively low level in different animals. In lymph node cells, transcripts for V beta 6, -8.2, and -9 were detected in four out of seven animals. The data indicate that in collagen-induced arthritis there is a restrictive usage of TCR V beta elements and that V beta 6 and -8.2 are probably used preferentially. PMID- 1311092 TI - The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. AB - Interactions among growth factors, cells, and extracellular matrix are critical to the regulation of directed cell migration and proliferation associated with development, wound healing, and pathologic processes. Here we report the association of PDGF-AB and -BB, but not PDGF-AA, with the extracellular glycoprotein SPARC. Complexes of SPARC and 125I-labeled PDGF-BB or -AB were specifically immunoprecipitated by anti-SPARC immunoglobulins. 125I-PDGF-BB and AB also bound specifically to SPARC that was immobilized on microtiter wells or bound to nitrocellulose after transfer from SDS/polyacrylamide gels. The binding of PDGF-BB to SPARC was pH-dependent; significant binding was detectable only above pH 6.6. The interaction of SPARC with specific dimeric forms of PDGF affected the activity of this mitogen. SPARC inhibited the binding of PDGF-BB and PDGF-AB, but not PDGF-AA, to human dermal fibroblasts in a dose-dependent manner. The expression of SPARC and PDGF was minimal in most normal adult tissues but was increased after injury. Enhanced expression of both PDGF-B chain and SPARC was seen in advanced lesions of atherosclerosis. We suggest that the coordinate expression of SPARC and PDGF-B-containing dimers following vascular injury may regulate the activity of specific dimeric forms of PDGF in vivo. PMID- 1311093 TI - Viral small nuclear ribonucleoproteins bind a protein implicated in messenger RNA destabilization. AB - Herpesvirus saimiri (HVS) is one of several primate viruses that carry genes for small RNAs. The five H. saimiri-encoded U RNAs (HSURs) are the most abundant viral transcripts expressed in transformed marmoset T lymphocytes. They assemble with host proteins common to spliceosomal small nuclear ribonucleoproteins (snRNPs). HSURs 1, 2, and 5 exhibit sequences at their 5' ends identical to the AUUUA motif, which targets a number of protooncogene, cytokine, and lymphokine mRNAs for rapid degradation. We show that a 32-kDa protein previously demonstrated to bind to the 3' untranslated region of several unstable messages can be UV crosslinked specifically to HSUR 1, 2, and 5 transcripts in vitro, as well as to endogenous HSUR snRNPs. Our results suggest an unusual role for these viral snRNPs: HSURs may function to attenuate the rapid degradation of certain cellular mRNAs, thereby facilitating viral transformation of host T lymphocytes. PMID- 1311094 TI - Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes. AB - We have isolated a full-length cDNA for human carbonic anhydrase IV (CA IV) from a lambda gt10 human kidney cDNA library. The 1105-base-pair (bp) cDNA contains a 47-bp 5' untranslated region, a 936-bp open reading frame, and a 122-bp 3' untranslated region. The deduced amino acid sequence is colinear with the N terminal sequence and the sequence of several tryptic peptides of human lung CA IV. It includes an 18-amino acid signal sequence, a 260-amino acid region that shows 30-36% similarity with the 29-kDa cytoplasmic CAs (CA I, CA II, and CA III), and an additional 27-amino acid C-terminal sequence that ends in a 21-amino acid hydrophobic domain. Of the 17 "active site" residues that are highly conserved in other human CAs, 16 are also present in CA IV. Expression of the cDNA in COS cells produced a 35-kDa enzyme that was membrane associated, resistant to inactivation by SDS, contained no carbohydrate, and reacted on Western blots with antiserum to the 35-kDa CA IV from human lung. Treatment of membranes from transfected COS cells with phosphatidylinositol-specific phospholipase C released 20-30% of the expressed enzyme from membranes, indicating that at least 20-30% of the expressed enzyme was anchored to membranes by a glycosyl-phosphatidylinositol linkage. PMID- 1311096 TI - A BamHI repeat element is predominantly associated with the degenerating neo-Y chromosome of Drosophila miranda but absent in the Drosophila melanogaster genome. AB - In Drosophila miranda, females have two X1 and two evolving X2 chromosomes, and males have one of each of these two X chromosomes and a Y chromosome. In males, the homologue of the X2 chromosome, the neo-Y chromosome, is attached to the Y chromosome and is under the process of degenerative evolution. We have examined a developmentally regulated X2/neo-Y chromosome-linked gene, 549mr, of D. miranda and found that the neo-Y chromosome-linked copy of this gene (549mr-NY) contains an insertional DNA. We discovered that sequences similar to those in the insertional DNA are present in multiple copies in the genome of both sexes of D. miranda but are more abundant in the males. The insertional DNA also identified a 1.1-kilobase BamHI repeat that is present in at least 6-fold excess in the male genome as compared to the female. This BamHI repeat and similar DNA sequences are predominantly concentrated on the evolving neo-Y chromosome, but very few are found on the homologous X2 and other chromosomes. The BamHI repeat also hybridizes with 2.0- and 1.8-kb RNAs and many other RNA species, which together are also approximately 6-fold greater in males. No sequences similar to the BamHI repeat are found in Drosophila melanogaster. Moreover, the BamHI repeat is not homologous to P, copia, or other D. melanogaster transposable elements. This repeat, named the NY element, may be involved in gene disruption and the process of degenerative evolution of the neo-Y chromosome. PMID- 1311095 TI - Cytotoxic and viral neutralizing antibodies crossreact with streptococcal M protein, enteroviruses, and human cardiac myosin. AB - The development of autoimmunity in certain instances is related to infectious agents. In this report, cytotoxic monoclonal antibodies (mAbs) that recognize epitopes on both enteroviruses and the bacterium Streptococcus pyogenes are described. Murine anti-streptococcal mAbs that were crossreactive with streptococcal M protein, human cardiac myosin, and other alpha-helical coiled coil molecules were found to neutralize coxsackieviruses B3 and B4 or poliovirus type 1. The viral-neutralizing anti-streptococcal mAbs were also cytotoxic for heart and fibroblast cell lines and reacted with viral capsid proteins on a Western immunoblot. Alignment of amino acid sequences shared between streptococcal M protein, coxsackie-virus B3 capsid protein VP1, and myosin revealed 40% identity in a 14- to 15-amino acid overlap. Synthetic peptides containing these sequences blocked mAb reactivity with streptococcal M protein. The data show that antibodies against alpha-helical structures of bacterial and viral antigens can lead to cytotoxic reactions and may be one mechanism to explain the origin of autoimmune heart disease. PMID- 1311097 TI - (125I)iodoazidococaine, a photoaffinity label for the haloperidol-sensitive sigma receptor. AB - A carrier-free radioiodinated cocaine photo-affinity label, (-)-3-(125I)iodo-4 azidococaine [(125I)IACoc], has been synthesized and used as a probe for cocaine binding proteins. Photoaffinity labeling with 0.5 nM (125I)IACoc resulted in selective derivatization of a 26-kDa polypeptide with the pharmacology of a sigma receptor in membranes derived from whole rat brain, rat liver, and human placenta. Covalent labeling of the 26-kDa polypeptide was inhibited by 1 microM haloperidol, di(2-tolyl)guanidine (DTG), 3-(3-hydroxyphenyl)-N-(1 propyl)piperidine (3-PPP), dextromethorphan, and carbetapentane. Stereoselective protection of (125I)IACoc photolabeling by 3-PPP [(+)-3-PPP more potent than (-) 3-PPP] was observed. (125I)IACoc labeling of the 26-kDa polypeptide was also inhibited by 10 microM imipramine, amitriptyline, fluoxetine, benztropine, and tetrabenazine. The size of the (125I)I-ACoc-labeled proteins is consistent with the size of proteins photolabeled in guinea pig brain and liver membranes by using the sigma photolabel azido-[3H]DTG. Kinetic analysis of (125I)IACoc binding to rat liver microsomes revealed two sites with Kd values of 19 and 126 pM, respectively. The presence or absence of proteolytic inhibitors during membrane preparation did not alter the size of the photolabeled sigma receptor, indicating that the 26-kDa polypeptide was not derived from a larger protein. In summary, (125I)IACoc is a potent and highly specific photoaffinity label for the haloperidol-sensitive sigma receptor and will be useful for its biochemical and molecular characterization. PMID- 1311098 TI - The third gamma subunit of the gamma-aminobutyric acid type A receptor family. AB - Cloned cDNAs encoding a member of the gamma-aminobutyric acid type A receptor gamma-subunit class were isolated from rat-brain-mRNA-derived libraries. The gamma 3 mRNA is present in cortex, claustrum, caudate putamen, and some thalamic nuclei, particularly the medial geniculate nucleus, where it is the predominant gamma-subunit transcript. The gamma 3 gene is expressed at very low levels in cerebellum and hippocampus. In coexpression experiments with the alpha 1 and beta 2 subunits, gamma 3 imparts benzodiazepine binding to gamma-aminobutyric acid type A receptors and forms gamma-aminobutyric acid-gated benzodiazepine-modulated chloride channels that exhibit a larger conductance than alpha 1 beta 2 receptor channels. Furthermore, the presence of gamma 3 in place of gamma 2 in alpha 1 beta 2 gamma x receptors generates a marked decrease in the affinity of agonists while leaving the affinity of antagonists or negative modulators largely unaffected. PMID- 1311099 TI - Carbachol-activated calcium entry into HT-29 cells is regulated by both membrane potential and cell volume. AB - Intracellular Ca2+ ([Ca2+]i) was measured in single Cl(-)-secretory HT-29/B6 colonic carcinoma cells with the Ca2+ probe fura-2 and digital imaging microscopy. Resting [Ca2+]i was 63 +/- 3 nM (n = 62). During treatment with the muscarinic agonist carbachol, [Ca2+]i rapidly increased to 901 +/- 119 nM and subsequently reached a stable level of 309 +/- 23 nM, which depended on Ca2+ entry into the cells from the extracellular solution. The goal of this study was to characterize the Ca2+ entry pathway across the cell membrane with respect to its dependence on membrane potential and cell volume. Under resting conditions [Ca2+]i showed no apparent dependence on either potential or cell volume. After stimulating Ca2+ entry with carbachol (100 microM), [Ca2+]i increased with hyperpolarization (low-K+ or valinomycin treatment) and decreased with depolarization (high-K+ or gramicidin treatment) of the cell, as expected from changes in driving force for Ca2+ entry. In stimulated cells, hypotonic solutions caused [Ca2+]i to increase, whereas hypertonic solutions blocked Ca2+ entry. The shrinkage-induced decreases in [Ca2+]i were only slightly affected when the membrane potential was increased with valinomycin, suggesting that shrinkage directly affects the carbachol-activated Ca2+ conductance. In contrast, the swelling-induced increase in [Ca2+]i was significantly reduced in valinomycin treated cells, suggesting an indirect dependence on a swelling-activated K+ conductance. Thus, carbachol-stimulated Ca2+ entry is under the dual control of membrane potential and cell volume. This mechanism may serve as a regulatory influence that determines the extent of Ca2+ influx during cholinergic stimulation. PMID- 1311100 TI - Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors. AB - A full-length cDNA clone encoding a glutamate receptor was isolated from a human brain cDNA library, and the gene product was characterized after expression in Xenopus oocytes. Degenerate PCR primers to conserved regions of published rat brain glutamate receptor sequences amplified a 1-kilobase fragment from a human brain cDNA library. This fragment was used as a probe for subsequent hybridization screening. Two clones were isolated that, based on sequence information, code for different receptors: a 3-kilobase clone, HBGR1, contains a full-length glutamate receptor cDNA highly homologous to the rat brain clone GluR1, and a second clone, HBGR2, contains approximately two-thirds of the coding region of a receptor homologous to rat brain clone GluR2. Southern and PCR analysis of a somatic cell-hybrid panel mapped HBGR1 to human chromosome 5q31.3 33.3 and mapped HBGR2 to chromosome 4q25-34.3. Xenopus oocytes injected with in vitro-synthesized HBGR1 cRNA expressed currents activated by glutamate receptor agonists with the following specificity sequence: domoate greater than kainate much greater than quisqualate greater than or equal to alpha-amino-3-hydroxy-5 methyl-4-isoxazole propionic acid greater than or equal to L-glutamate much greater than N-methyl-D-aspartate. The kainate-elicited currents were specifically blocked by 6-cyano-7-nitroquinoxaline-2,3-dione but were insensitive to 2-amino-5-phosphonovalerate and kynurenic acid. These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain. PMID- 1311101 TI - Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. AB - We have recently described the properties of direct repeats (DRs) of the half site AGGTCA as hormone response elements (HREs). According to our results, spacing the half sites by 3, 4, or 5 nucleotides determines specificity of response for vitamin D3, thyroid hormone, and retinoic acid receptors, respectively. This so-called 3-4-5 rule led to the prediction that remaining spacing options of 0, 1, and 2 might serve as targets for other nuclear receptors. A concurrent prediction is that receptors recognizing common sites might display more complex or combinatorial interactions. In exploring these predictions, we discovered that both the retinoid X receptor (RXR) and COUP-TF bind preferentially to a DR-1 motif. In vivo, RXR and COUP-TF display antagonistic action such that RXR-mediated activation is fully repressed by COUP TF. In vitro studies reveal that COUP-TF and RXR form heterodimers on DR-1. Thus, these results support a general proposal in which the half-site spacing preferences may be used as a means to decipher potentially complex and interactive regulatory circuits. PMID- 1311103 TI - Effect of DuP 753, a nonpeptide angiotensin II receptor antagonist, on the drinking responses to acutely administered dipsogenic agents in rats. AB - The present studies examine the effect of the nonpeptide angiotensin II (AII) type 1 receptor antagonist, DuP 753, on water intake in rats treated with dipsogenic stimuli, which are thought to induce drinking via release of renin and subsequent formation of AII. Subcutaneous administration of DuP 753 in doses that are known to inhibit drinking induced by AII failed to inhibit the water intake of rats following subcutaneous administration of the beta-adrenoceptor agonist isoproterenol. The peptide antagonist1 Sar, 8Ileu-AII, which blocks both AII type 1 and AII type 2 receptors, also failed to inhibit isoproterenol-induced drinking, suggesting that neither subtype is involved in this drinking response. Additional studies verified previous reports that acute subcutaneous administration of both the beta-adrenoceptor antagonist propranolol and the angiotensin I-converting enzyme inhibitor captopril could block the drinking response to subcutaneous administration of isoproterenol. Subcutaneous administration of DuP 753 also failed to inhibit the drinking responses to subcutaneous administration of serotonin, 5-hydroxytryptophan, hypertonic saline, and polyethylene glycol. However, central intraventricular administration of DuP 753 inhibited the drinking response to subcutaneous administration of isoproterenol. The results are discussed in terms of the importance of AII in mediating isoproterenol-, serotonin-, and 5-hydroxytryptophan-induced water intake and suggest a need to readdress this mechanism. PMID- 1311102 TI - Mutually exclusive exon splicing of the cardiac calcium channel alpha 1 subunit gene generates developmentally regulated isoforms in the rat heart. AB - Several clones were isolated from a rat genomic library in order to further characterize a region of variability within the third membrane-spanning region of the fourth motif (IVS3) of the L-type voltage-dependent calcium channel. We report here that this diversity arises from alternative splicing of a primary transcript containing a single pair of adjacent exons each encoding a unique sequence for the IVS3 region. Definitive proof of a mutually exclusive splicing mechanism was obtained by genomic mapping of flanking upstream and downstream exons and by extensive sequence analysis of the relevant exon/intron boundaries. S1 nuclease protection experiments revealed that both variant forms of the IVS3 were equally expressed in newborn and fetal rat heart, whereas only a single isoform predominated in adult rat heart. The results demonstrate the existence of an important developmentally regulated switch mediated by alternatively spliced exons in cardiac tissue at a time when major changes in excitation occur. PMID- 1311104 TI - Electrogenic anion absorption in rabbit distal colon. AB - The mechanisms of anion transport in the rabbit distal colon were investigated in vitro under short-circuit conditions by examining the effects of transport inhibitors (the stilbene derivatives SITS and DIDS) under a variety of conditions. These agents consistently inhibited Jm-sCl: SITS (10(-3) M) reduced both unidirectional chloride fluxes to the same degree and did not alter JnetCl. In contrast, 10(-4) M DIDS had no effect on Js-mCl and had a significant chloride antiabsorptive effect. DIDS had no effect on either tissue cyclic AMP levels or on basal flux of potassium. The effects of SITS and the cyclic AMP-related secretagogue theophylline on Isc were independent. Additionally, there was no significant alteration of intracellular potential difference or apical membrane fractional resistance elicited by SITS during microelectrode impalement of colonic surface epithelial cells. These results suggest a complex mechanism of anion transport in the distal colon, with a component of electrogenic anion absorption inhibited by the stilbenes. The subsequent changes in current, conductance, and chloride fluxes are dependent upon additional, independent anion transport processes. These pharmacologic agents exhibit an antiabsorptive effect, rather than a stimulation of electrogenic chloride secretion. PMID- 1311105 TI - delta 9-Tetrahydrocannabinol suppresses macrophage extrinsic antiherpesvirus activity. AB - The effect of delta 9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, on macrophage intrinsic and extrinsic antiherpesvirus activities was examined. THC had no effect on the capacity of the macrophage-like cells RAW264.7, J774A.1, and P388D1 to take up virus. In addition, replication of virus within macrophages did not occur regardless of drug treatment, indicating that THC had no effect on macrophage intrinsic antiviral activity. In contrast, the cannabinoid exerted a dose-dependent inhibition of macrophage extrinsic antiviral activity. This activity describes that macrophage function by which these cells suppress virus replication within xenogeneic cells in an interferon independent manner. The inhibitory effect of THC on extrinsic antiviral activity was greatest on RAW264.7 and J774A.1 cells, followed by P388D1 cells. These macrophage-like cells regained their extrinsic antiviral activity in a time related fashion following removal of the drug. These results indicate that THC inhibits macrophage extrinsic antiherpesvirus activity, but has no effect on intrinsic antiviral activity. However, the suppressive effect of THC on extrinsic antiviral activity is reversible upon removal of the drug. PMID- 1311106 TI - Effects of respiratory motion on dose uniformity with a charged particle scanning method. AB - A three-dimensional spot-scanning technique for radiotherapy with protons is being developed at the Paul Scherrer Institute. As part of the effort to optimize the design and ensure clinically useful dose distributions, a computer simulation of the dose deposition in the presence of respiratory motion was performed. Preliminary experiments have characterized the proton beam and the scanning procedure. Using these parameters, the computer program calculated the dose within a uniform volume of water in the presence of respiratory motion. Respiration amplitude, respiration period, respiration direction, number of fractions, size and position of the beamspots and rescanning multiplicity were systematically varied and the effect on the dose distribution determined. The dose uniformity is very dependent on the direction of the respiration relative to the three independent beam scanning directions. The dose uniformity decreases with increasing respiration amplitude, but has little response to changes in respiration frequency. Rescanning the volume, such as with fractionation, improves the dose uniformity roughly as the square root of the number of fractions. Broad, Gaussian beams result in better dose uniformity than narrow, sharply delineated ones, but produce slower dose fall-off at the edges of the scanned volume. Results of this work are being incorporated into the design of the system. PMID- 1311107 TI - Conditioned facilitatory modulation of the response to an aversive stimulus in the crab Chasmagnathus. AB - A mild electrical shock delivered to the walking legs of the crab Chasmagnathus granulatus through a fine layer of sea water, induces a running response that declines after repeated stimulation. Herein, a first series of experiments was aimed at conditioning the response to a light or a dark pulse, but no detectable CR was disclosed during training nor in a later test with the CS alone, even though several stimulus parameters were assayed. In a second series, crabs were repeatedly exposed during training to a light pulse (CS) immediately followed by shock (UCS), and after a 6-h rest interval, tested with either CS-UCS or UCS. The CS-UCS presentation at testing elicited a higher recovery (potentiated recovery, circa 70%) than that evoked by the UCS alone (unconditioned recovery, circa 35%) (Experiment 3). An experiment including the explicitly unpaired control procedure (Experiment 4), confirmed that the enhanced response (CR) to the shock (UCS) (measured as potentiated recovery) is conditioned to an illumination signal (CS). An alternative explanation of the potentiated recovery in terms of retardation of habituation proved hardly tenable (Experiment 5). In Experiment 6, crabs were exposed to a variety of light pulse shock and dark pulse shock temporal relationships, and results were found consistent with a delay of reinforcement gradient when light termination was considered as CS. Thus a decrease in luminance is able to become associated with shock and to condition an enhanced response regardless of light termination being the offset of a light pulse or the onset of a dark pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311108 TI - Inhibition of mesencephalic morphine analgesia by methysergide in the medial ventral medulla of rats. AB - The neural substrates of endogenous supraspinal opioid pain inhibition are mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). To ascertain whether a serotonergic synapse participated in this pathway, the present study determined whether microinjections of methysergide into the NRM or NRGC would alter analgesia elicited by morphine microinjections into the PAG. Morphine (2.5 micrograms) in the PAG and immediately adjacent areas produced significant analgesia on the tail flick and jump tests in rats. Pretreatment with the serotonin receptor antagonist methysergide (0.5-5 micrograms) in either the NRM or NRGC significantly reduced morphine analgesia elicited from the PAG by 69% on the tail-flick and by 50% on the jump tests without altering basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support this antagonistic effect. These data indicate that a ventro-medial medullary serotonergic synapse participates in the transmission of opioid pain-inhibitory signals from the PAG. PMID- 1311109 TI - Lithium chloride and immunomodulation in taste aversion conditioning. AB - Lithium chloride has been used in many studies of conditioning to induce taste aversion behaviour, and in some experiments investigating conditioning effects on immunity it has been used on the assumption that it is immunologically neutral. The studies reported here, however, indicate that LiCl is not immunologically neutral and when used to endow a UCS with noxious properties to enhance the behavioural response in taste aversion conditioned immunosuppression, it may antagonize the residual immunosuppression following initial UCS administration and also the conditioned immunosuppression occurring after CS reexposure. Therefore, conclusions drawn from studies of behaviourally conditioned immunomodulation where LiCl is used as part of either the CS or UCS may require reevaluation. PMID- 1311110 TI - Enhanced dopamine metabolism in accumbens leads to motor activity and concurrently to increased output from nondopamine neurons in ventral tegmental area and substantia nigra. AB - We previously have reported that nondopamine (non-DA) neurons in substantia nigra (SN) and ventral tegmental area (VTA) of the rat show increased discharge rates during amphetamine (AMPH) and apomorphine (APO)-induced motor activity. The present study represents an attempt to determine the contribution of nucleus accumbens (ACC) dopaminergic activity to these effects, and to ascertain whether the effects in VTA differ from those seen in SN when dopaminergic activity is enhanced locally in ACC. The experiments were carried out in male albino rats (300-400 g) chronically implanted with multiple fine wire electrodes (62 microns) aimed at the pars reticulata of SN (SNR) and VTA. Unit activity was recorded extracellularly in the behaving rat, from neurons identified on the basis of the properties of their action potentials as representing the output of the non-DA neurons in these two structures. In each drug session, unit activity was recorded in parallel from several probes, while motor activity was measured with the open ended wire technique. But with the recording technique used, a unit represented in most instances the output of a small family of neurons (3-10). Each animal underwent a series of tests given on consecutive days. During these tests, motor and unit activity were measured for 90 min before the drug was administered, and for 135 min after. The first test was of the effects of AMPH, 5 mg/kg, given by the systemic route. The second was of the effects of saline containing 0.1% ascorbic acid (the vehicle) injected bilaterally in ACC, in a volume of 2 microliters per side. The third and all subsequent tests were of the effects of a mixture containing 40 micrograms AMPH, 20 micrograms DA, and 20 micrograms pargyline (P) dissolved in 2 microliters of the vehicle, injected bilaterally in ACC. The results showed that systemic AMPH made the animal hyperactive and at the same time, increased the discharge rate of the non-DA neurons. The bilateral injections of the vehicle in ACC, increased motor activity for about 7 min, an effect interpreted as a rebound from the restraint of the animal during the intracerebral injections, and then depressed motor throughout the 135 min of the postinjection recording period. The effect of the vehicle was to depress unit activity. The effects of injecting the mixture in ACC was to increase motor activity, but with the magnitude and duration of the increase depending on the number of treatments received.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311111 TI - NGC-evoked nociceptive behaviors: I. Effect of nucleus gigantocellularis stimulation. AB - The role of the nucleus gigantocellularis (NGC) in nociception was examined by investigating behavioral responses that are supported by NGC stimulation in rats. Analyses indicated that NGC stimulation will support escape, active avoidance, and increases in behaviors that are thought to reflect fear in rats. A variety of behavior patterns were elicited by NGC stimulation, including gross peripheral motor movements such as walking, circling and rearing, and specific orofacial movements such as eye closure, ear movement, jaw opening and facial muscle contractions. No major differences in avoidance, affect, or escape behaviors were revealed between the various electrode placements, suggesting functional homogeneity within this neural region. The results of this study suggest that NGC stimulation generates several components of nociception, including behavioral arousal, autonomic nervous system-mediated responses, aversive affect, and motor responses. PMID- 1311112 TI - NGC-evoked nociceptive behaviors: II. Effect of midbrain and thalamus lesions. AB - Alterations in nociceptive behaviors evoked by stimulation of the nucleus gigantocellularis (NGC) were observed following lesions of the dorsal central gray (DCG) or parafascicularis nucleus (PF) in rats. Lesions of the DCG decreased affective responses and facilitated extinction of avoidance responding associated with NGC stimulation. Lesions of the PF disrupted escape and avoidance responding to NGC stimulation, although postlesion training improved avoidance but not escape performance. The NGC, without its rostral connections to the DCG or PF, does not generate sufficient information for either aversive affective responses or locomotor escape responses that are associated with stimulation of this structure. In contrast, the elicited motor reactions do not depend upon these rostral structures. This supports a role for NGC neurons in functions related to motor, rather than to affective or complex behavioral components of nociception. The differential disruption of the more complex behaviors by DCG and PF lesions provides behavioral evidence for functional differentiation of a nociceptive system involving the relay of information from the NGC to these rostral areas. PMID- 1311113 TI - Bacterial resistances to inorganic mercury salts and organomercurials. AB - Environmental and clinical isolates of mercury-resistant (resistant to inorganic mercury salts and organomercurials) bacteria have genes for the enzymes mercuric ion reductase and organomercurial lyase. These genes are often plasmid-encoded, although chromosomally encoded resistance determinants have been occasionally identified. Organomercurial lyase cleaves the C-Hg bond and releases Hg(II) in addition to the appropriate organic compound. Mercuric reductase reduces Hg(II) to Hg(O), which is nontoxic and volatilizes from the medium. Mercuric reductase is a FAD-containing oxidoreductase and requires NAD(P)H and thiol for in vitro activity. The crystal structure of mercuric ion reductase has been partially solved. The primary sequence and the three-dimensional structure of the mercuric reductase are significantly homologous to those of other flavin-containing oxidoreductases, e.g., glutathione reductase and lipoamide dehydrogenase. The active site sequences are the most conserved region among these flavin-containing enzymes. Genes encoding other functions have been identified on all mercury ion resistance determinants studied thus far. All mercury resistance genes are clustered into an operon. Hg(II) is transported into the cell by the products of one to three genes encoded on the resistance determinants. The expression of the operon is regulated and is inducible by Hg(II). In some systems, the operon is inducible by both Hg(II) and some organomercurials. In gram-negative bacteria, two regulatory genes (merR and merD) were identified. The (merR) regulatory gene is transcribed divergently from the other genes in gram-negative bacteria. The product of merR represses operon expression in the absence of the inducers and activates transcription in the presence of the inducers. The product of merD coregulates (modulates) the expression of the operon. Both merR and merD gene products bind to the same operator DNA. The primary sequence of the promoter for the polycistronic mer operon is not ideal for efficient transcription by the RNA polymerase. The -10 and -35 sequences are separated by 19 (gram-negative systems) or 20 (gram-positive systems) nucleotides, 2 or 3 nucleotides longer than the 17 nucleotide optimum distance for binding and efficient transcription by the Escherichia coli sigma 70-containing RNA polymerase. The binding site of MerR is not altered by the presence of Hg(II) (inducer). Experimental data suggest that the MerR-Hg(II) complex alters the local structure of the promoter region, facilitating initiation of transcription of the mer operon by the RNA polymerase. In gram-positive bacteria MerR also positively regulates expression of the mer operon in the presence of Hg(II). PMID- 1311114 TI - Capsular hematoma as a late complication in breast reconstruction with silicone gel prostheses. AB - This paper presents a rare complication of breast reconstruction with silicone gel prostheses in which formation of intracapsular hematomas in the mammary region occurred 3 years after surgery. Treatment by bilateral capsular excision was successful. The rarity of this occurrence and the progress of the case are the major reasons for this publication. PMID- 1311115 TI - MR imaging of thoracic disease: clinical uses. PMID- 1311117 TI - Postprocedural symptoms in children who undergo imaging studies of the urinary tract: is it the contrast material or the catheter? AB - The frequency, nature, and duration of postprocedural symptoms in 100 children who underwent voiding cystourethrography (VCUG) after administration of 17.2% wt/vol iothalamate meglumine, 100 children who underwent radionuclide cystography (RNC) after administration of saline and technetium-99m pertechnetate, and 28 children catheterized before diuretic renal scintigraphy (DRS) were prospectively assessed with telephone follow-up. All children were aged 2 years or older; 61 were boys, 167 were girls. Postprocedural symptoms occurred in 80 children (35.1%). The frequency of postprocedural symptoms was nearly identical in the VCUG group and the two other groups. Boys (n = 33 [54%]) had symptoms significantly more often than girls (n = 47 [28%]) (P less than or equal to .0005). Dysuria was the most common symptom (n = 75 [32.9%]) and was frequently accompanied in younger children by anxiety over going to the bathroom. Symptoms disappeared within 24 hours in 32 of 80 children (40%) and lasted 4-10 days in eight children. It is concluded that most postprocedural symptoms in children who undergo VCUG, RNC, or DRS are secondary to catheterization rather than to the use of iodinated contrast material. PMID- 1311116 TI - Therapeutic effect of transcatheter oily chemoembolization therapy for encapsulated nodular hepatocellular carcinoma: CT and pathologic findings. AB - An emulsion of iodized oil and doxorubicin hydrochloride was intraarterially injected in 27 patients with encapsulated single nodular hepatocellular carcinoma (HCC). Computed tomography (CT) was performed 1-3 weeks after injection, and the lesions were resected 1-4 weeks thereafter. The percentages of tumor necrosis were evaluated in cut surfaces of resected specimens and were compared with the findings at iodized-oil CT. Six tumors with complete intratumor retention of iodized oil had 98% necrosis, and 21 tumors with incomplete retention had 64% necrosis. Two tumors with complete retention of iodized oil in the surrounding liver had 100% necrosis, while 16 tumors with partial retention and nine tumors without retention of iodized oil in surrounding liver had 74% and 62% necrosis, respectively. Complete retention of iodized oil in the tumor and surrounding liver demonstrated the best therapeutic effects. Evaluation of the pattern and distribution of iodized oil in the tumor and surrounding liver with iodized-oil CT is useful in the assessment of the therapeutic effects of transcatheter arterial embolization in encapsulated nodular HCCs. PMID- 1311118 TI - Breast cancer: reliability of mammographic appearance as a predictor of hormone receptor status. AB - The association of mammographic appearance with hormone receptor status was investigated in 397 patients with primary breast cancers. The mammographic appearance was classified as type 1, spiculated (n = 159); type 2, structural changes (density) (n = 102); type 3, calcifications (n = 30); type 4, circumscribed opacity (n = 65); and type 5, not visible on mammogram (n = 41). Univariate analysis showed a significant association with estrogen receptor (ER) status for age (less than 50 vs greater than or equal to 50 years), tumor TNM category (those in category 1 vs those in higher categories), and mammographic appearance; with progesterone receptor status, the association was significant only for age. Multivariate analysis adjusted for potential confounders confirmed a significant association between ER status and mammographic appearance (ER status was more likely with type 1 than with the other mammographic types), but the strength of the association was limited. The mammographic appearance of breast cancer is not a reliable method to predict hormone receptor status for clinical purposes. PMID- 1311119 TI - Liver tumors: follow-up with P-31 MR spectroscopy after local chemotherapy and chemoembolization. AB - The authors examined and quantified the changes observed in the phosphorus-31 magnetic resonance (MR) spectra of liver tumors after chemotherapy and chemoembolization to investigate the suitability of P-31 MR spectroscopy for follow-up. A 1.5-T unit was used before and at specific times during therapy to obtain spectra of liver tumors in 10 patients with liver metastases from colorectal carcinoma and two patients with hepatocellular carcinoma. A marked increase in inorganic phosphate and a decrease in the alpha- and beta-nucleotide phosphate portions of the spectra were observed during the first few hours after local chemotherapy or chemoembolization. Later, the phosphomonoester signals increased markedly and the phosphodiester signals decreased slightly. The effects of successful chemoembolization or local chemotherapy become apparent in the P-31 MR spectrum during the first few hours after the start of therapy. The results demonstrate that P-31 MR spectroscopy is a suitable method for follow-up. However, long-term studies are needed to determine whether it also yields prognostic information. PMID- 1311120 TI - Receptors and endogenous ligands. Implications for addiction. PMID- 1311121 TI - The effectiveness of drug treatment. PMID- 1311122 TI - Brain mechanisms of drug-induced reinforcement. AB - The results of the experiments described above suggest that although the abused psychomotor stimulants and opioids have independent actions that contribute to their reinforcing effects, there are common neuronal substrates for some of their rewarding effects. Additionally there is considerable evidence implicating dopamine systems in these rewarding effects. The neuronal systems involved in these pharmacological actions may be similar to those involved in the rewarding effects of electrical stimulation to the brain. Although both classes of compounds cause euphoria in humans and are reinforcing in animals, the opioids are also central nervous system depressant drugs. These depressant properties influence the subjective effects in humans and possibly the nature of the rewarding effect in animals. Experiments using the 2-deoxyglucose procedure indicate that BSR to either the ventral tegmental area or the medial forebrain bundle results in functional activation throughout the mesocorticolimbic system. The major effects are found in the nucleus accumbens, olfactory tubercle, and the medial prefrontal cortex. Cocaine produces increases in metabolic rates similar in distribution to BSR. Morphine, however, only causes significant increases in functional activity in the olfactory tubercle. Further, only in this brain site did the combination of BSR plus morphine or cocaine cause increases in functional activity over that of stimulation alone. These findings suggest that the olfactory tubercle plays a major role in the pharmacological actions of both the psychomotor stimulants and the opioids as well the rewarding effects of electrical stimulation of the brain. PMID- 1311124 TI - Medical groups frustrate CDC hit-list plans. PMID- 1311123 TI - Neurobiological mechanisms in cocaine and opiate dependence. PMID- 1311125 TI - [Hepatitis-C virus and hepatoma]. AB - To clarify the relationship between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC), frozen serum samples from 213 patients with histologically proven liver cirrhosis alone (96 alcoholics, 59 HBsAg positive, 29 non-A, non-B hepatitis, 29 cryptogenic) and 40 patients with liver cirrhosis and HCC (12 alcoholics, 7 HBsAg positive, 7 non-A, non-B hepatitis, 14 cryptogenic) were analyzed for antibodies to hepatitis C virus (anti-HCV) with the ortho-HCV ELISA. The results were as follows. 50 of 253 (20%) patients were anti-HCV positive. The prevalence of anti-HCV was significantly higher in patients with HCC than in patients without HCC (14 of 40 [35%] vs 36 of 213 [17%]; p less than 0.001). In anti-HCV-positive patients HCC were significantly more frequent than in anti-HCV-negative patients (14 of 50 [28%] vs 26 of 203 [13%]; p less than 0.001). The significantly higher occurrence of HCC in anti-HCV-positive patients was not related to other known risk factors such as alcoholism or chronic hepatitis B virus (HBV) infection. Patients with HCV infection as the only risk factor also had a significantly higher occurrence of HCC (12 of 38 [32%] vs 26 of 203 [13%]; p less than 0.001). Our data suggest that chronic HCV infection plays an important role in the pathogenesis of HCC, in particular in patients with cirrhosis unrelated to alcohol or HBV infection. PMID- 1311126 TI - [Anti-HCV test in patients with chronic non-A, non-B hepatitis]. AB - Our study was designed to evaluate the clinical significance of the ELISA-anti HCV test. 90 patients with histologically proven chronic non-A, non-B hepatitis (NANBH) and a control group consisting of 36 patients with primary biliary cirrhosis (PBC) were analyzed for antibodies to hepatitis C virus (anti-HCV). Frozen serum samples were tested with the ortho-HCV-ELISA. 67 of 90 (74%) patients with chronic NANBH showed antibodies to the hepatitis C virus. The prevalence of anti-HCV in patients with parenterally transmitted and sporadic chronic NANBH was 70% (23 of 33) and 77% (44 of 57) and in patients with chronic active and chronic persistent NANBH 73% (27 of 37) and 76% (40 of 53) respectively. No significant difference in the prevalence of anti-HCV in the 4 subgroups of patients with chronic NANBH was found. 2 of 36 patients (6%) with PBC were anti-HCV positive without evidence of previous HCV infection. Our results bear out the experience of other authors, that HCV is the commonest pathogen of chronic NANBH. The low prevalence of anti-HCV in patients with PBC suggests good specificity. There have been reports in the literature of "false positive results", particularly in autoimmune hepatitis, and it has been shown that borderline positive test results are often unspecific and therefore to be interpreted with care. PMID- 1311127 TI - Gating of the cardiac Ca2+ release channel: the role of Na+ current and Na(+) Ca2+ exchange. AB - In cardiac myocytes, calcium influx through the calcium channel is the primary pathway for triggering calcium release. Recently it has been suggested that the calcium-induced calcium release mechanism can also be activated indirectly by the sodium current, which elevates the sodium concentration under the cell membrane, thereby favoring the entry of "trigger" calcium via the sodium-calcium exchanger. To test this hypothesis, sodium current was suppressed by reducing the external sodium concentration or applying tetrodotoxin. At potentials positive to -30 millivolts, calcium release was unaffected. A small calcium release at more negative potentials could be attributed to partial activation of calcium channels, because it was unaltered by replacement of sodium with lithium and was blocked by cadmium. Thus, sodium influx or its accumulation does not initiate calcium release. In addition, sodium-calcium exchange-related calcium release at potentials positive to +80 millivolts has slower kinetics than calcium channel induced release. Therefore, only the calcium channel gates the fast release of calcium from the sarcoplasmic reticulum in the range of the action potential. PMID- 1311128 TI - Tyrosyl phosphorylation and activation of MAP kinases by p56lck. AB - T cell signaling via the CD4 surface antigen is mediated by the associated tyrosyl protein kinase p56lck. The 42-kilodalton mitogen-activated protein (MAP) kinase (p42mapk) was tyrosyl-phosphorylated and activated after treatment of the murine T lymphoma cell line 171CD4+, which expresses CD4, with antibody to CD3. Treatment of the CD4-deficient cell line 171 with the same antibody did not result in phosphorylation or activation of p42mapk. Purified p56lck both tyrosyl phosphorylated and stimulated the seryl-threonyl phosphotransferase activity of purified p44mpk, a MAP kinase isoform from sea star oocytes. A synthetic peptide modeled after the putative regulatory phosphorylation site in murine p42mapk (Tyr185) was phosphorylated by p56lck with a similar Vmax, but a fivefold lower Michaelis constant (Km) than a peptide containing the Tyr394 autophosphorylation site from p56lck. MAP kinases may participate in protein kinase cascades that link Src family protein-tyrosyl kinases to seryl-threonyl kinases such as those encoded by rsk and raf, which are putative substrates of MAP kinases. PMID- 1311130 TI - Activators of protein kinase C increase the phosphorylation of the synapsins at sites phosphorylated by cAMP-dependent and Ca2+/calmodulin-dependent protein kinase in the rat hippocampal slice. AB - Previous studies have shown that activators of protein kinase C (C kinase) produce synaptic potentiation in the hippocampus. For example, the C kinase activator phorbol dibutyrate has been shown to increase transmitter release in the hippocampus. In addition, a role for C kinase in long-term potentiation has been proposed. A common assumption in such studies has been that substrates for C kinase were responsible for producing these forms of synaptic potentiation. However, we have recently shown that phorbol dibutyrate increased the phosphorylated of synapsin II (formerly protein III, Browning et al., 1987) in chromaffin cells (Haycock et al., 1988). Synapsin II is a synaptic vesicle associated phosphoprotein that is a very poor substrate for C kinase but an excellent substrate for cAMP-dependent and Ca2+/calmodulin-dependent protein kinase. We felt, therefore, that activation of C kinase might lead to activation of a kinase cascade. Thus effects of C kinase activation might be produced via the phosphorylation of proteins that are not substrates for C kinase. In this report we test the hypothesis that activators of C kinase increase the phosphorylation of synapsin II and an homologous protein synapsin I. Our data indicate that PdBu produced dose-dependent increases in the phosphorylation of synapsin I and synapsin II. We also performed phospho-site analysis of synapsin I using limited proteolysis. These studies indicated that PdBu increased the phosphorylation of multiple sites on synapsin I. These sites have previously been shown to be phosphorylated by both cAMP-dependent protein kinase and the multifunctional Ca2+/calmodulin-dependent protein kinase II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311129 TI - Multiple heteroreceptors on limbic thalamic axons: M2 acetylcholine, serotonin1B, beta 2-adrenoceptors, mu-opioid, and neurotensin. AB - Ligand binding to many transmitter receptors is much higher in layer Ia of rat posterior cingulate cortex than it is in other layers, and this is where most axons from the anterior thalamus terminate. The present study explores the possibility that a number of receptors may be expressed on axons from limbic thalamic nuclei that terminate in layer Ia. Unilateral thalamic lesions were placed in rats and, 2 weeks later, five ligand binding protocols, coverslip autoradiography, and single grain counting techniques were used to quantify binding in control and ablated hemispheres. Binding to the following receptor subtypes was analyzed: M2 acetylcholine, 3H-oxotremorine-M, or 3H-AF-DX 116 with 50 nM pirenzepine; serotonin1B, 125I-(-)-cyanopindolol with 30 microM isoproterenol; beta 2-adrenoceptors, 125I-(-)-cyanopindolol with 1 microM serotonin and 10 microM atenolol; mu-opioid, 3H-T[r-D-Ala-Gly-MePhe-Gly-ol; neurotensin, 3H-neurotensin. Thalamic lesions reduced binding in two laminar patterns. In one pattern, there was a major reduction in binding in most superficial layers with that in layer Ia ranging from 50 to 70% for binding to M2 muscarinic and serotonin1B receptors. Binding to beta 2-adrenoceptors was also reduced in most superficial layers but to a lesser extent. In the second pattern, reductions were limited to layer I with losses in layer Ia of 20-30% for mu opioid and neurotensin receptors. In no instance was layer Ia binding completely abolished (i.e., postlesion peaks remained). Since the transmitters for each of the five receptors analyzed in this study are not synthesized by anterior or laterodorsal thalamic neurons, these receptors are heteroreceptors. The greatest postlesion reduction in M2 binding was for AF-DX 116 and so most M2 heteroreceptors are of the "cardiac" subtype. Finally, the diverse population of heteroreceptors on limbic thalamic axons provides for presynaptic modulation by a wide range of transmitter systems and suggests that thalamocortical transmission may not be a simple, unmodulated event. PMID- 1311131 TI - Evaluation of a protease activation mutant of Sendai virus as a potent live vaccine. AB - A protease activation mutant of Sendai virus, TR-5, was investigated as a candidate for a live vaccine. Vaccination with TR-5 which had been activated by chymotrypsin beforehand (active TR-5) elicited protective immunity against otherwise lethal challenge infection with wild-type Sendai virus in DBA/2, C3H and ICR strains of mice. Less of the active TR-5 was required to confer protection on mice compared with an ordinary ether-inactivated Sendai virus vaccine (split vaccine). The protective immunity elicited by TR-5 lasted longer and the booster effect was more prominent compared to the split vaccine. No seroconversion was observed with contact mice when housed in a cage with mice vaccinated with the active TR-5. The overall results show that the active TR-5 is an effective and safe live vaccine of Sendai virus in mice. PMID- 1311133 TI - Application of the polymerase chain reaction to the detection of bovine viral diarrhea virus infections in cattle. AB - We used the polymerase chain reaction (PCR) technique to detect bovine viral diarrhea virus (BVDV) infections in cattle. Of 120 cattle screened in this study, 29 were scored positive for BVDV with both PCR and conventional virus isolation. Ninety cattle were negative in both assays. One cow was scored positive for BVDV with the PCR but was negative with virus isolation. In dilution experiments PCR analysis was at least 10 times more sensitive than BVDV isolation. PMID- 1311132 TI - Rapid identification and differentiation of the vaccine strain Rac H from EHV 1 field isolates using a non-radioactive DNA probe. AB - A method for rapid differentiation between the EHV 1 live vaccine strain Rac H and field isolates is described. Total DNA was isolated from virus-infected small scale cell cultures. DNA fragments digested with restriction endonuclease BamHI were separated, transferred and immobilized on filter membranes. A Digoxigenin labeled probe derived from EHV 1 was used for hybridization. This probe hybridized specifically to sequences of the inverted terminal repeat region which in case of Rac H include a deletion of 0.8 kb. By comparing the different migration patterns after blot hybridization it could be shown that in 65 isolates from cases of abortion the live vaccine strain Rac H was not involved. PMID- 1311135 TI - Induction of host cell protein synthesis by human herpesvirus 6. AB - We observed an increase in host cell protein synthesis in human cord blood lymphocytes (CBL) infected with human herpesvirus 6 relative to uninfected cultures. The magnitude of this effect could not be explained by a smaller decrease in cell number in the infected cultures. The induction of host cell protein synthesis by HHV-6 does not appear to be mediated by a stable soluble factor present in the infected cell culture supernatant. When CBL were infected with virus that had been exposed to ultraviolet irradiation (UV) for various intervals, we found that the level of increase in cell number, host protein synthesis, viral DNA and viral antigen was inversely proportional to the length of time of virus exposure to UV. No increase in cell number or host cell protein synthesis was seen in CBL infected in the presence of 50 micrograms/ml phosphonoacetic acid, an inhibitor of HHV-6 DNA replication. These results indicate that components of input virions do not induce the increased protein synthesis and that the induction is dependent on viral DNA replication. PMID- 1311134 TI - The Papanicolaou smear. PMID- 1311136 TI - Expression of herpes simplex virus type 1 glycoprotein B in insect cells. Initial analysis of its biochemical and immunological properties. AB - A recombinant baculovirus (vAc-gB1) was constructed which expresses the glycoprotein B (gB) gene of herpes simplex virus type 1 (HSV-1). When Sf9 cells were infected with these recombinant viruses, a protein that was close in size to authentic HSV-1 gB was detected by gB polyclonal antibody. The recombinant gB was found on the membrane of Sf9 cells and was susceptible to tunicamycin, glycosidase F (PNGase F) and partially susceptible to Endo-H. Antibodies raised in mice to this recombinant recognized viral gB and neutralized the infectivity of HSV-1 in vitro. Mice inoculated with the recombinant gB were protected from lethal challenge with HSV-1. PMID- 1311137 TI - Evolution of the fusion protein gene of human parainfluenza virus 3. AB - The nucleotide sequences of the fusion (F) gene of 15 clinical strains of human parainfluenza virus 3 (HPIV3) isolated between 1959 and 1987 were compared with the F gene sequence of the prototype strain, Wash/47885/57. Nucleotide sequence diversity was greatest in the noncoding regions of the F gene; however, regions believed to function as transcriptional signals were completely conserved. Amino acid sequences were highly conserved and all but a few amino acid substitutions were conservative in nature. Sequence comparisons indicate heterogeneity in HPIV3 F genes; however, a significant proportion of nucleotide changes are maintained after they first appear and seem to be accumulating with time. Phylogenetic analysis suggests that there are 2 lineages of HPIV3 in North America. The two lineages can be distinguished by specific amino acid differences in the F protein, which correlate with differences in antigenic properties and neutralization patterns of HPIV3. The pattern of HPIV3 evolution, based on the analysis of F gene sequences, most closely resembles that of influenza virus B, vesicular stomatitis virus and Newcastle disease virus. PMID- 1311138 TI - Liver resection for primary neoplasms. AB - Resection is the treatment of choice for almost all hepatic neoplasms. Improvements in operative techniques and perioperative patient management have resulted in low morbidity and mortality. Patients with underlying chronic liver disease in association with hepatic malignancy now can be offered either subsegmental resection or liver transplantation in selected cases. The role of cryosurgery and alcohol injection in patients who are not candidates for resection should become clearer once longer follow-up data are available. PMID- 1311140 TI - Ewing's bone sarcoma, paternal occupational exposure, and other factors. AB - To determine risk factors for Ewing's bone sarcoma, the authors interviewed mothers of 43 patients diagnosed between January 1978 and August 1986 and 193 controls in the San Francisco Bay Area, California, regarding medical and occupational history of parents and other factors related to the subjects and their immediate families. Controls were selected by using random digit dial telephone methods. Adjusted relative risk estimates suggest that risks were elevated for children whose fathers were engaged in agricultural occupations during the period from 6 months prior to conception of the subject up to the time of diagnosis for the patients or interview for the controls (relative risk (RR) = 8.8, 95% confidence interval (CI) 1.8-42.7) and for children whose fathers had occupational exposure to herbicides, pesticides, or fertilizers (RR = 6.1, 95% CI 1.7-21.9, p = 0.002). Prior ingestion of poison or an overdose of medication was more common in patients than in controls (RR = 4.4, 95% CI 1.4-13.5). These and other findings should be investigated in larger population-based studies to determine specific factors that may account for the associations. PMID- 1311139 TI - Search for Coxsackievirus B3 RNA in idiopathic dilated cardiomyopathy using gene amplification by polymerase chain reaction. AB - A polymerase chain reaction (PCR) amplification assay was developed to detect Coxsackievirus B3 ribonucleic acid (RNA) in blood and myocardial tissue of explanted hearts from 40 patients who underwent cardiac transplantation and in 1 normal heart. Twenty-one patients were affected by idiopathic dilated cardiomyopathy of different duration and 19 by coronary artery disease. Coxsackievirus B3 in vitro infected Vero cells and cells infected by related human enteroviruses (Coxsackievirus B2, B4, and poliovirus 1) were used as reaction controls. PCR was performed using 4 pairs of primers homologous to Coxsackie-virus B3 sequences. Three sets were located in regions of the genome conserved at nucleotide level between several enterovirus species (replicase gene, 5' noncoding region), while one was located in a Coxsackievirus B3-specific region (VP1 gene). Total RNA was prepared by acid guanidinium isothiocyanate extraction from tissue stored frozen at -80 degrees C. One microgram of total RNA was retrotranscribed with either antisense primer or with random hexanucleotide primers and then subjected to 40 cycles of amplification. PCR products were separated by electrophoresis on a 10% polyacrylamide gel, electrotransferred to a nylon membrane and then hybridized to oligonucleotide probes specific for the coxsackievirus B3 genome radiolabeled with radioactive isotope of phosphorous. All pairs of primers yielded specific amplification products when tested on Coxsackievirus B3-infected Vero cells, with a sensitivity of 1 infected cell out of 10(5) to 10(6) cells starting from 1 microgram total RNA. Primer sets for regions of Coxsackievirus B3 genome highly conserved between related enteroviral species gave positive amplification also when challenged with RNA from cells infected by Coxsackievirus B2, B4 and poliovirus 1. PMID- 1311141 TI - Prospects for the primary prevention of breast cancer. AB - In this paper, the rationale, stage of development, and known or potential adverse effects of three potential strategies for the prevention of breast cancer are reviewed. Two methods--the use of tamoxifen in postmenopausal women and the use of luteinizing hormone (LH)-releasing hormone agonists in premenopausal women -involve hormonal manipulation. In the premenopausal period, the goal is to reduce the number of ovulatory menstrual cycles a woman experiences in order to reduce her exposure to estrogen and progesterone. Physical activity during adolescence is proposed as a nonhormonal method of accomplishing this. The use of LH-releasing hormone agonists to produce a reversible menopause can also reduce a woman's cumulative exposure to ovarian steroid hormones. Tamoxifen, which is effective in breast cancer therapy, provides endocrine control of estrogen regulated breast tumor growth. Breast cancer chemoprevention trials using tamoxifen among postmenopausal women have been proposed, and pilot studies are under way. PMID- 1311143 TI - Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. AB - Plasma thrombomodulin (TM) levels were significantly elevated at disease onset in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC), but was not in those with essential thrombocythemia and idiopathic thrombocytopenic purpura. However, in patients with TTP and DIC, TM levels decreased significantly after they achieved complete remission. In both TTP and DIC patients, plasma TM levels at onset in those with poor prognosis were higher than that in those with good prognosis. Among DIC patients, the plasma TM level was higher in those with organ failure than in those without, but there were no differences among patients with various underlying diseases associated with DIC. It is speculated that the plasma TM level reflects damage to vascular endothelial cells or organ failure and that it is useful in assessing prognosis for patients with DIC and TTP. PMID- 1311142 TI - Cigarette smoking and the risk of anogenital cancer. AB - The association between cigarette smoking and cervical cancer has been demonstrated in numerous prior studies. As part of population-based case-control studies of cancers of the vulva, vagina, cervix, anus, and penis in relation to infection with human papillomavirus, conducted in western Washington State and the province of British Columbia from the mid 1980s until the present time, the authors have collected detailed information on smoking history. The proportion of subjects who were current smokers of cigarettes ranged from slightly over 40% among incident cases of vaginal and cervical cancer to 60% among cases of vulvar and anal cancer. In contrast, only about 25% of controls were current smokers. The adjusted odds ratios (OR) associated with current smoking were substantially elevated (OR = 1.9-14.6) for all cancer sites except cancer of the vagina (OR = 1.3). The risks tended to increase in proportion to the number of cigarettes smoked. For most cancer sites, the odds ratios associated with former smoking were substantially less than those associated with current smoking and diminished with increasing time since cessation of smoking. The authors' data and those of other investigators suggest that cigarette smoking plays a role in the etiology of anogenital cancers and that smoking has a late-stage or promotional effect. PMID- 1311144 TI - Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation. AB - Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation. PMID- 1311145 TI - Expression of high affinity binding sites for erythropoietin on L8057 cells, a mouse megakaryoblastic cell line, associated with cell differentiation. AB - In this study, specific binding sites were examined for erythropoietin (EPO) on the mouse leukemic cell line, L8057. This cell line is megakaryoblastic in origin as evidenced by an enlargement of cell size, multinuclearity, intense activity of acetylcholinesterase, more expression of glycoprotein IIb and IIIa antigen, and higher ploidy distribution after the treatment with 12-o-tetradecanoylphorbor-13 acetate (TPA). The original undifferentiated cells possessed a single class of low affinity binding sites for recombinant human (rh) EPO with a Kd of 3.5 nM. Following the treatment with TPA, high affinity binding sites (Kd; 440 pM) were expressed in addition to the low affinity sites. EPO stimulated the incorporation of 3H-leucine into TPA-treated L8057 cells, and the maximal effect of EPO was observed at the same order as the Kd value of high affinity sites. The present data demonstrates that the expression of high affinity binding sites for EPO is associated with the differentiation of L8057 cells which have megakaryocytic characteristics. Furthermore, protein synthesis stimulated by EPO may be mediated through the high affinity sites. PMID- 1311146 TI - Acute megakaryoblastic leukemia with translocation t(1;22)(p13;q13) in a 10-week old infant. AB - A 10-week-old girl without Down syndrome developed an acute megakaryoblastic leukemia (AMKL). Bone marrow aspirates and biopsy showed megakaryoblastic infiltration with myelofibrosis. The diagnosis was made based on the findings that the positive reactions of leukemic cells to platelet peroxidase and to monoclonal antibodies which recognize platelet-specific surface glycoprotein (GP) IIb/IIIa and GP78. The blasts also showed myeloid and monocytoid differentiation antigens. The leukemic cells had a karyotype of 46,XX,t(1;22)(p13;q13). Our case and two other infantile cases reported by other investigators establish the novel association of the t(1;22) with AMKL. PMID- 1311148 TI - Acrylamide monomer and peripheral neuropathy in chemical workers. AB - The relationship between exposure to acrylamide monomer and neurological outcomes was investigated in 82 chemical industry workers. Vibrotactile thresholds were determined quantitatively with a Vibratron II device, using forced choice and method of limits procedures. Symptoms of numbness, limb pain, peeling skin, and sweating hands had significantly higher prevalences in the exposed than in the unexposed group. Signs of peeling skin and sweating hands were significantly more common in the exposed group. Vibration thresholds were not associated with exposure. PMID- 1311147 TI - Fibrous minerals in the lungs of mesothelioma patients: comparison between data on SEM, TEM, and personal interview information. AB - To determine and compare the fiber types and size distributions in the lung tissue of mesothelioma patients in Finland, samples from 29 patients with known work history were analyzed with transmission electron microscopy (TEM) and X-ray microanalysis. Compared with the earlier results using scanning electron microscopy (SEM), the fiber concentrations were about three times as high and ranged from 0.1 million to 5,200 million fibers per gram of dry tissue. In 15 patients (52%), crocidolite/amosite were the dominating fiber types, representing more than 70% of all fibers. Anthophyllite asbestos was the most prevalent fiber type in eight patients (28%), and it was found in the samples of 13 patients (45%). One-half of the anthophyllite fibers were longer than 5 microns, whereas other fiber types were somewhat smaller. PMID- 1311150 TI - Fatal maternal laryngeal papillomatosis in pregnancy: a case report [corrected]. AB - Although genital condylomata worsen with pregnancy, we are unaware of any reports of fatal maternal laryngeal papillomatosis. A maternal death at 20 weeks' gestation of a patient with chronic laryngeal papillomatosis is described. Pregnant patients with a history of this disorder who have symptoms should be considered candidates for immediate evaluation. PMID- 1311149 TI - Gelsolin gene mutation--at codon 187--in familial amyloidosis, Finnish: DNA diagnostic assay. AB - Familial amyloidosis, Finnish (FAF), is an autosomal dominant form of systemic amyloidosis with lattice corneal dystrophy and progressive cranial neuropathy as principal clinical manifestations. We have shown that the novel amyloid fibril protein found in these patients is an internal degradation fragment of gelsolin, an actin-binding protein, and that it contains an amino acid substitution, asparagine for aspartic acid at position 15, that is due to a guanine-to-adenine transversion corresponding to codon 187 of human plasma gelsolin cDNA. To test that this mutation cosegregates with the disease high-molecular-weight genomic DNA was isolated from autopsied tissues or lymphocytes of 23 patients, 6 healthy relatives and 20 unrelated healthy control persons. Specific fragments were amplified with the polymerase chain reaction for oligonucleotide hybridization analysis using the slot-blot technique. The guanine-to-adenine transversion was found in all FAF patients tested, but in none of the control subjects. Our results show that the mutation (G to A) cosegregates with the disease phenotype, and that the slot-blot analysis can be used as a diagnostic assay, including prenatal evaluation. PMID- 1311151 TI - Evaluating the treatment of sexually transmitted diseases at an urban public hospital outpatient clinic. AB - Sexually transmitted diseases occur disproportionately among the poor, are often treated in public hospitals and clinics, and have not been subjected to quality of-care evaluation. We designed a medical record abstraction system using well established, specific process-of-care criteria drawn from the medical literature and experts and grouped into three levels of quality: excellent, adequate, and minimal. One hundred seventy-six consecutive patients were identified from the clinic logbook and their medical records abstracted. Deficiencies in history taking, physical examination, laboratory testing, treatment, and public health reporting were identified. PMID- 1311152 TI - Evaluation of a self-help dietary intervention in a primary care setting. AB - BACKGROUND: Dietary intervention to reduce fat consumption and increase fiber consumption has been recommended by the National Cancer Institute, but there is little evidence concerning the effectiveness of self-help materials. The purpose of this study was to evaluate such self-help materials, introduced by a nurse in a primary care setting. METHODS: A randomized controlled trial involving 242 subjects was conducted in two primary care clinics in Chapel Hill, NC, in 1987. Changes in fat and fiber consumption in the intervention and control groups during the 3-month interval between interviews were compared using analysis of covariance. RESULTS: The estimated reduction in fat was 3.8g larger for the intervention group than for the control group, but the confidence interval included zero. For those individuals who had some responsibility for meal preparation there was a larger difference (-6.9g) in favor of the intervention group, although the difference using calorie-adjusted values was -3.8g with a 95% confidence interval (-7.1, -0.4). The differences for fiber change were smaller. CONCLUSIONS: We found significant small but consistent differential changes associated with a minimal self-help intervention, but we cannot rule out the possibility of some response bias. Nonetheless, this study demonstrates that the use of self-help materials for dietary change is feasible, and may be effective. PMID- 1311153 TI - Nutrition: the need to define "optimal" intake as a basis for public policy decisions. AB - Much of the current chronic disease incidence, notably coronary artery disease and certain types of cancer, relates to nutritionally induced metabolic overload. The evidence for this conclusion is based on extensive analytical, descriptive, and metabolic epidemiological investigations as well as critical experimental studies in animals. Dietary assessments within homogenous populations, because of inherent measurement errors and similarities in eating habits, make only limited contributions to this issue. This communication makes recommendations as to an "optimal" diet, especially for fats and fibers, as a goal for effective disease prevention that is within our reach with the appropriate support of an informed public and a cooperative food industry. To facilitate effective public health action, the "optimal" diet is called the 25/25 diet, that is, 25% of calories as fat and 25 g per day of fiber. PMID- 1311154 TI - Daphnetin: a novel antimalarial agent with in vitro and in vivo activity. AB - Daphnetin is a dihydroxycoumarin that is being used in China for the treatment of coagulation disorders. It is also a chelator and an antioxidant. In vitro, daphnetin causes a 50% inhibition (IC50) of 3H-hypoxanthine incorporation by Plasmodium falciparum at concentrations between 25 and 40 microM. Several related compounds, such as scopoletin, 2, 3-dihydroxybenzoic acid and 3, 4 dihydroxybenzoic acid show no inhibitory activity. The antimalarial activity of daphnetin is inhibited by the addition of iron. Daphnetin does not appear to be an oxidant drug, since it does not spontaneously generate superoxide in vitro. However, it does alkylate bovine serum albumin when incubated in the presence of iron. In vivo, daphnetin significantly prolongs survival of P. yoelli-infected mice. PMID- 1311155 TI - The epidemiology of hepatitis C virus antibody in Yemen. AB - A cross-sectional survey of 348 subjects without evidence of liver disease was conducted to investigate the prevalence and risk factors for hepatitis C virus antibody (anti-HCV) seropositivity in the Yemen Arab Republic. The mean age of study subjects was 28.7 years (range 3-80), and 61% were males. Using commercial enzyme-linked immunosorbent assays (ELISA), 6.0% (95% confidence interval [CI] 3.8-9.1) of subjects were anti-HCV-positive, 13.5% were hepatitis B surface antigen-positive (HBsAg-positive), and 51.4% were positive for at least one serologic marker of prior hepatitis B infection. Nine (2.6%; 95% CI 1.2-4.9) of the 21 ELISA-positive sera were confirmed to be anti-HCV positive by a recombinant immunoblot assay. Anti-HCV seropositivity was significantly associated with age (odds ratio [OR] 2.0 for each 10-year increase in age) and prior surgery (OR 10.1), but was not associated with a history of prior blood transfusion or markers of hepatitis B infection. These preliminary data suggest that hepatitis C may pose a substantial health threat in Yemen. PMID- 1311156 TI - Anticoagulant drugs and central nerve blockade. PMID- 1311157 TI - Three-dimensional structure of cytidine monophosphatase reactive trans-Golgi elements in spinal ganglion cells of the rat. AB - In order to analyse, at the electron microscope level, the three-dimensional configuration of the trans compartment of the Golgi apparatus rat dorsal root ganglia were treated to demonstrate cytidine monophosphatase (CMPase) activity. The localization of enzymatic activity in the Golgi apparatus varied according to cell types. In type A and C cells, CMPase was exclusively located in the transmost sacculotubular element, whereas in type B cells all the saccules of the stacks forming the Golgi ribbon and the trans-Golgi networks were impregnated. Numerous dense bodies seen at proximity were also CMPase positive. In 3 microns thick sections of type A cells examined at low magnification, the impregnated element was scattered throughout the cytoplasm and never formed a continuous structure. In type B cells, the strongly reactive trans-Golgi networks did not follow the entire length of the impregnated Golgi ribbon but were preferentially located in the concavity of its arched portions. At higher magnification and in all cell types some tubular portions of the trans-Golgi networks took the appearance of spheroidal cage-like structures, the CMPase positive anastomotic tubules forming the bars of the cage. Anastomotic tubules separated from the trans-Golgi networks formed fenestrated spheres, while nearby CMPase-reactive dense bodies exhibited a paler hilus. These observations were taken to indicate that in ganglion cells, some CMPase positive dense bodies, presumably lysosomes, formed by fragmentation of the trans-Golgi networks. PMID- 1311158 TI - Massive diphenhydramine poisoning resulting in a wide-complex tachycardia: successful treatment with sodium bicarbonate. AB - Diphenhydramine poisoning is characterized most often by anticholinergic effects. Cardiotoxicity and circulatory collapse have rarely been reported after massive ingestions of diphenhydramine and other H1-receptor-blocking agents, although these substances have local anesthetic properties and have been studied as antiarrhythmics. We report the case of a patient who developed a wide-complex tachycardia as a complication of acute diphenhydramine poisoning that responded to IV sodium bicarbonate. PMID- 1311159 TI - DNA topoisomerase I from calf thymus mitochondria is associated with a DNA binding, inner membrane protein. AB - During purification of the type I DNA topoisomerase from calf thymus mitochondria, two polypeptides, p78 and p63, cofractionate with the enzymatic activity (Lazarus et al., (1987) Biochemistry 26, 6195-6203). The two polypeptides are released from a mitochondrial inner membrane preparation by nonionic detergent lysis and both adsorb strongly to a single-stranded DNA agarose column. We have attempted to characterize the relationship between these two polypeptides and have found the following: (i) the mitochondrial topoisomerase is active in free (monomer) and associated (heterodimer) form; (ii) the catalytic activity resides solely in p78, as adjudged by both the covalent linkage of the enzyme to substrate DNA and the ability of the enzyme to relax supercoils; (iii) at low ionic strength the enzyme is active in monomer form with p78 alone being sufficient for activity; (iv) in high salt, the high molecular weight species is a 140-kDa heterodimer composed of one p78 and one p63; and (v) the two polypeptides are not structurally related as digestion with V8 protease results in distinct proteolytic fragment patterns. These results suggest that p63 may have an important role in the metabolism of the mitochondrial topoisomerase. PMID- 1311160 TI - The bacterial hemoglobin from Vitreoscilla can support the aerobic growth of Escherichia coli lacking terminal oxidases. AB - Two Escherichia coli mutants that lack both cytochrome o and d terminal oxidases are able to grow with glucose as the carbon source but not with the aerobic substrates succinate or lactate. One of these, GV101, is a deletion mutant of cytochrome o and a point mutation of cytochrome d. The other, GK100, is a total deletion mutant of all the genes for both cytochromes. When these mutants were transformed with a plasmid containing the gene for the bacterial hemoglobin from Vitreoscilla, they were capable of growth in the presence of succinate or lactate and showed aerobic respiration in the presence of these substrates, unlike the parent strains. Cells transformed with a plasmid containing the gene for the hemoglobin but lacking the native promoter did not express the hemoglobin and did not respire. Membrane vesicles prepared from the cells consumed oxygen in the presence of succinate. This succinate-supported respiration decreased with successive washings of the vesicles but was restored by adding E. coli cytosol containing the hemoglobin or by adding the hemoglobin purified from Vitreoscilla. This respiration was inhibited by cyanide. PMID- 1311161 TI - Anomalous effect of uncouplers on respiratory chain-linked transhydrogenation in Escherichia coli membranes: evidence for a localized proton pathway? AB - Energization of the pyridine nucleotide transhydrogenase in everted membrane vesicles from Escherichia coli JM83 was compared with the process in vesicles of the same strain transformed with the plasmid pDC21 overexpressing this enzyme. Proton translocation was assayed by the quenching of the fluorescence of the probe quinacrine. Agents able to discharge transmembrane proton gradients such as nigericin and the uncouplers 3,3',4',5-tetrachlorosalicylanilide and carbonyl cyanide m-chlorophenylhydrazone inhibited ATP-dependent transhydrogenation of NADP by NADH and discharged transmembrane proton gradients generated by transhydrogenation of AcNAD by NADPH, by oxidation of NADH, and by hydrolysis of ATP. This was observed in everted membrane vesicles of both strains JM83 and JM83pDC21. These strains differed significantly in the response of the NADH oxidation-dependent transhydrogenase. This reaction was inhibited by nigericin and uncouplers in membrane vesicles of JM83 but there was little inhibition or the reaction was stimulated in JM83pDC21, in spite of the discharge of the NADH oxidation-generated proton gradient measured by quinacrine fluorescence in the latter strain. It is proposed that the transhydrogenase is energized by direct or local (nonbulk phase) proton translocation in membranes of this strain. Uncouplers might facilitate these routes but would not discharge them. The generality of these observations was shown using other strains. NADH oxidase activity was severalfold lower in membrane vesicles of JM83pDC21 compared with JM83. The levels of ubiquinone and cytochromes, and the activities of NADH dehydrogenases I and II, and of cytochrome oxidase, were similar in the two strains. It is concluded that the NADH oxidase activity of JM83pDC21 is low because of the reduced rate of collision between electron-transferring complexes of the respiratory chain due to the large amount of transhydrogenase protein in the membranes of this strain. The large amount of transhydrogenase favors direct, nonbulk phase proton transfer. Transhydrogenase activity was stimulated by Ca2+, Mg2+, or Mn2+. PMID- 1311162 TI - 25Mg NMR studies of yeast enolase and rabbit muscle pyruvate kinase. AB - 25Mg NMR spectroscopy was used to study the interactions of the activating cations with their respective binding sites in the enzymes yeast enolase and rabbit muscle pyruvate kinase (PK). Titration of Mg2+ with enolase allows for the calculation of 1/T2 for Mg2+ bound at site I of 1510 s-1 and a quadrupolar coupling constant chi = 0.30 MHz. Titration of Mg2+ with enolase in the presence of 2-phosphoglycerate (PGA) and Zn2+, where Zn2+ binds specifically at site I, gives a 1/T2 for Mg2+ bound at site II of 4000 s-1 (chi = 0.49 MHz). The Mg2+ at site II appears to be more anisotropic than Mg2+ at site I. The titration of site I of the enolase-Mg-PGA-Mg complex with Zn2+ or Mn2+ shows a simple displacement of the Mg2+. No paramagnetic effects by Mn2+ on 25Mg relaxation were observed. Temperature studies of the 25Mg resonance show that fast exchange of the Mg2+ occurs under these conditions. From the lack of a paramagnetic effect, the distance between the cations at sites I and II must be more than 6-9 A. This distance limits the location, hence the function, of the cation at site II for catalytic activity. Titration of Mg2+ with PK gives a 1/T2 for bound Mg2+ of 2200 s-1 (chi = 0.24 MHz). A titration of Mg2+ with PK in the presence of the inhibitor oxalate gives a 1/T2 of 400 s-1. The temperature dependence of 25Mg relaxation in the PK-Mg-oxalate complex is consistent with slow exchange (Ea = 6.1 +/- 1.6 kcal/mol). The enzyme-bound cation is more tightly sequestered by the addition of a ligand that binds directly to the cation. An investigation of the 25Mg relaxation in the PK-Mn-oxalate-Mg-ATP complex, where the Mg2+ is bound to the nucleotide and the Mn2+ was enzyme bound, was not successful due to precipitation of PK under experimental conditions and the short T2 relaxation for 25Mg in this complex. The applications of 25Mg NMR have been useful in partially describing the properties of the bound Mg2+ in these two metal-requiring enzymes. PMID- 1311163 TI - Increased NADH-dependent production of reactive oxygen intermediates by microsomes after chronic ethanol consumption: comparisons with NADPH. AB - Microsomes from chronic ethanol-fed rats were previously shown to catalyze the NADPH-dependent production of reactive oxygen intermediates at elevated rates compared to controls. Recent studies have shown that NADH can also serve as a reductant and promote the production of oxygen radicals by microsomes. The current study evaluated the influence of chronic ethanol consumption on NADH dependent microsomal production of reactive oxygen intermediates, and compared the results with NADH to those of NADPH. Microsomal oxidation of chemical scavengers, taken as a reflection of the production of hydroxyl radical (.OH) like species was increased about 50% with NADH as cofactor and about 100% with NADPH after chronic ethanol consumption. The potent inhibition of the production of .OH-like species by catalase suggests a precursor role for H2O2 in .OH production. Rates of NADH- and NADPH-dependent H2O2 production were increased by about 50 and 70%, respectively, after chronic ethanol consumption. A close correlation between rates of H2O2 production and generation of .OH-like species was observed for both NADH and NADPH, and increased rates of H2O2 production appear to play an important role in the elevated generation of .OH-like species after chronic ethanol treatment. Microsomal lipid peroxidation was elevated about 60% with NADH, and 120% with NADPH, after ethanol feeding. With both types of microsomal preparations, the characteristics of the NADH-dependent reactions were similar to the NADPH-dependent reactions, e.g., sensitivity to antioxidants and free radical scavengers and catalytic effectiveness of ferric complexes. However, rates with NADPH exceeded the NADH-dependent rates by 50 to 100%, and the increased production of reactive oxygen intermediates by microsomes after ethanol treatment was greater with NADPH (about twofold) than with NADH (about 50%). Oxidation of ethanol results in an increase in hepatic NADH levels and interaction of NADH, iron, and microsomes can produce potent oxidants capable of initiating lipid peroxidation and oxidizing .OH scavengers. These acute metabolic interactions produced by ethanol-derived NADH are increased, not attenuated, in microsomes from chronic ethanol-fed rats, and it is possible that such increases in NADH (and NADPH)-dependent production of reactive oxygen species play a role in the development of oxidative stress in the liver as a consequence of ethanol treatment. PMID- 1311164 TI - Deferoxamine inhibition of Cr(V)-mediated radical generation and deoxyguanine hydroxylation: ESR and HPLC evidence. AB - Electron spin resonance (ESR) and high-performance liquid chromatography (HPLC) techniques were utilized to investigate the effect of deferoxamine on free radical generation in the reaction of Cr(V) with H2O2 and organic hydroperoxides. ESR measurements demonstrated that deferoxamine can efficiently reduce the concentration of the Cr(V) intermediate as formed in the reduction of Cr(VI) by NAD(P)H or a flavoenzyme glutathione reductase/NADH. ESR spin trapping studies showed that deferoxamine also inhibits Cr(V)-mediated .OH radical generation from H2O2, as well as Cr(V)-mediated alkyl and alkoxy radical formation from t-butyl hydroperoxide and cumene hydroperoxide. HPLC measurements showed that .OH radicals generated by the Cr(VI)/flavoenzyme/NAD(P)H enzymatic system react with 2'-deoxyguanine to form 8-hydroxy-2'-deoxyguanine (8-OHdG), a DNA damage marker. Deferoxamine effectly inhibited the formation of 8-OHdG also. PMID- 1311165 TI - Purification and characterization of bovine interstitial collagenase and tissue inhibitor of metalloproteinases. AB - In this report we describe the purification of bovine interstitial collagenase and provide information on its substrate specificity, kinetic parameters of catalytic activity, and amino terminal protein sequence. In addition, we present a simplified protocol for the purification of bovine tissue inhibitor of metalloproteinases (TIMP). Collagenase was purified by sequential chromatography through heparin-Sepharose, DEAE-Sepharose, and green-agarose, resulting in a product that was greater than 95% pure as judged by polyacrylamide electrophoresis. Typical of other interstitial collagenases, the isolated bovine protein was activated by protease and organomercurial treatment. It also demonstrated a kinetics and substrate specificity similar to those of human collagenase. TIMP was purified by sequential chromatography through heparin Sepharose and DEAE-Sepharose followed by reverse-phase HPLC. The purified protein had a size, N-terminal sequence, and inhibitor activity similar to those of other mammalian TIMPs. Partial peptide sequences suggested that bovine collagenase and TIMP have strong sequence homology to their human homologues. PMID- 1311166 TI - Spin trapping study on the kinetics of Fe2+ autoxidation: formation of spin adducts and their destruction by superoxide. AB - The oxidation of Fe2+ was investigated by electron spin resonance spin trapping techniques with N-t-butyl-alpha-phenylnitrone (PBN) and dimethyl sulfoxide. Under pure oxygen, the spin adduct PBN/.OCH3 was rapidly generated by the addition of Fe2+ (0.2-1.2 mM) into phosphate buffer containing ethylenediaminetetraacetate (EDTA), dimethyl sulfoxide, and PBN at pH 7.4, but it decayed. The decay process of PBN/.OCH3 consists of two components. The fast decay was dependent on Fe2+ concentration. Another was due to destruction of the spin adduct by superoxide anion (.O2-), because superoxide dismutase (SOD) markedly prevented the decay. Catalase decreased the yield of PBN/.OCH3. When EDTA was replaced by diethylenetriaminepentaacetic acid (DTPA), both the generation and decay process of PBN/.OCH3 were slow. SOD and catalase effects were similar to those in EDTA. Fe2+ produced PBN/.OCH3 even in the absence of chelators. We could estimate the kinetic parameters by computer simulation, comparing the Fe2+ oxidation in EDTA with that in DTPA. These results demonstrate that Fe2+ reacts with O2 to generate .O2- and then H2O2, which produces .CH3 by reaction with Fe2+ and dimethyl sulfoxide.(.)OCH3 results from the reaction between .CH3 and O2. The adduct PBN/.OCH3 decays by reaction with Fe2+ and .O2-. PMID- 1311167 TI - Epithelioid component of uterine leiomyosarcoma simulating metastatic carcinoma. AB - A variant of uterine leiomyosarcoma containing two morphologic bell populations is described. A smooth-muscle component with a mitotic rate of 13 per 10 high power fields, and a second population of cells mimicking metastatic small-cell carcinoma were both present. The second population was composed of small angulated epithelioid cells with hyperchromatic nuclei and barely discernible cytoplasm growing in tight rows, often in single file between fascicles of smooth muscle. DNA flow cytometry showed a large tetraploid aneuploid tumor cell population, and further suggested that the epithelioid cells probably represent tetraploid tumor cells in S-phase. Thus, this morphologic variant of leiomyosarcoma, unlike previously described variants of smooth-muscle tumors, is explained by the variable appearance of the neoplastic cells in different phases of the cell cycle. PMID- 1311168 TI - Risk factors for the neurologic complications associated with aortic aneurysms. AB - We reviewed the incidence of neurologic complications in 200 consecutive patients with aortic aneurysm or aortic dissection. In this 2-year period, neurologic impairment developed in 18.5% of these patients, and in 10 patients neurologic dysfunction heralded aortic rupture or dissection. Those patients with abnormal neurologic examinations at presentation frequently had aneurysm rupture or dissection and a mortality rate of 54%. Patients with thoracic or thoracoabdominal aneurysms were more likely to have neurologic complications than those with abdominal aneurysms. The most common complications were focal central nervous system ischemia, followed by disorders of consciousness and peripheral nerve complications. In patients who had elective aneurysm resection, female sex, aneurysm location, and intraoperative hypotension were risk factors for focal central nervous system ischemia. We conclude that neurologic complications depend on aneurysmal location, occur at various levels of the nervous system, and frequently develop when the intraoperative mean arterial pressure falls below 55 mm Hg. PMID- 1311169 TI - Stimulus-response uncoupling in the neutrophil. Adenosine A2-receptor occupancy inhibits the sustained, but not the early, events of stimulus transduction in human neutrophils by a mechanism independent of actin-filament formation. AB - Generation of superoxide anion (O2-) in response to occupancy of neutrophil chemoattractant receptors requires both early events ('triggering') and sustained signals ('activation'). We have previously demonstrated that occupancy of adenosine A2 receptors inhibits O2- generation by neutrophils. In parallel, adenosine-receptor occupancy promotes association of bound N-formylmethionyl leucyl-phenylalanine (fMLP) receptors with the cytoskeleton, a process associated with termination of neutrophil activation (stimulus-response uncoupling). We undertook this study to determine whether inhibition of neutrophil function by adenosine-receptor occupancy requires intact actin filaments and to examine the effect of adenosine-receptor occupancy on the stimulated generation of intracellular signals involved in neutrophil triggering and activation. Occupancy of adenosine A2 receptors by 5'-N-ethylcarboxamidoadenosine (NECA, 1 microM) significantly increased (130 +/- 1% of control, P less than 0.001, n = 3) association of [3H]fMLP with cytoskeletal preparations. Cytochalasin B (5 micrograms/ml), an agent which disrupts actin filaments, completely blocked association of [3H]fMLP with cytoskeletal preparations, as previously reported. However, NECA markedly increased association of [3H]fMLP with the cytoskeleton even in the presence of cytochalasin B (P less than 0.0002). Moreover, NECA did not significantly affect either the early (30s) or the late (5 min) formation of actin filaments after stimulation by chemoattractant (fMLP, 0.1-100 nM). Cytochalasin B markedly inhibited actin-filament formation by stimulated neutrophils, and NECA did not reverse the effect of cytochalasin B on actin filament formation. Adenosine-receptor occupancy did not affect the rapid peak in diacylglycerol generation (less than or equal to 15 s) from either [3H]arachidonate- or [14C]glycerol-labelled phospholipid pools. However, as would be predicted if occupancy of the adenosine receptor was a signal for early termination of cell activation, NECA (1 microM) markedly diminished the slow sustained generation of diacylglycerol. These results suggest that adenosine-A2 receptor occupancy does not affect triggering of the neutrophil, but that occupancy of adenosine receptors is an early signal for the termination of neutrophil activation, i.e. the 'premature' finish of signal transduction. Moreover, these data indicate that at least two pathways are available for increasing the association of ligated chemoattractant receptors with the cytoskeleton of neutrophils: F-actin-dependent and -independent. PMID- 1311170 TI - Domain mapping of the retinal cyclic GMP phosphodiesterase gamma-subunit. Function of the domains encoded by the three exons of the gamma-subunit gene. AB - Retinal rod-outer-segment phosphodiesterase (PDE) is a heterotetramer consisting of two similar, but not identical, catalytic subunits (alpha and beta) and two identical inhibitory subunits (gamma 2). Previously, we have reported that the site of PDE alpha/beta interaction with PDE gamma is located within residues 54 87 [Cunnick, Hurt, Oppert, Sakamoto & Takemoto (1990) Biochem. J. 271, 721-727]. The site for PDE gamma interaction with transducin alpha (T alpha) was found to encompass residues 24-45 of PDE gamma [Morrison, Cunnick, Oppert & Takemoto (1989) J. Biol. Chem. 264, 11671-11681]. In order to identify binding sites and other functional domains of PDE gamma, the three peptides which are encoded by the three exons of the PDE gamma gene were synthesized chemically. These exons encode for residues 1-49, 50-62 and 63-87 of bovine PDE gamma [Piriev, Purishko, Khramtsov & Lipkin (1990) Dokl. Akad. Nauk. SSSR 315, 229-230]. The peptide encompassing residues 63-87 was inhibitory in a PDE assay, whereas peptides 1-49 and 50-62 had no effect. However, both peptides 1-49 and 63-87 bound to PDE alpha/beta in a solid-phase binding assay. Only peptide 1-49 bound to T alpha.GTP[S] (GTP[S] is guanosine 5'-[gamma-thio]triphosphate). These data confirm that the inhibitory region of PDE gamma is encoded by exon 3 (residues 63 87), whereas a separate binding site for PDE alpha/beta and for T alpha.GTP[S] is encoded by exon 1 (residues 1-49). To study further the structure-function relationship of PDE gamma, this entire protein and two mutants were chemically synthesized. One mutant (-CT) lacked residues 78-87, whereas another replaced tyrosine-84 with glycine (TYR-84). Whereas the synthetic PDE gamma inhibited PDE alpha/beta catalytic activity, the -CT and TVR-84 mutants did not. All three synthetic proteins bound to both PDE alpha/beta and and T alpha.GTP[S]. These data confirm the presence of an alternative binding site on PDE gamma and demonstrate the importance of tyrosine-84 in PDE gamma inhibitory activity. PMID- 1311171 TI - The gene for a novel protein, a member of the protein disulphide isomerase/form I phosphoinositide-specific phospholipase C family, is amplified in hydroxyurea resistant cells. AB - Cell lines selected in multiple steps for increasing resistance to hydroxyurea have been shown to have corresponding increases in ribonucleotide reductase activity. We have isolated a number of cDNA clones from a cDNA library constructed from a highly hydroxyurea-resistant hamster cell line, 600H, in which the activity of ribonucleotide reductase is elevated more than 80-fold. These clones correspond to genomic DNA sequences amplified in the 600H cell line compared with the V79 parental line. One of these cDNA clones, termed P5, codes for a 50 kDa protein detected by in vitro translation of poly(A)+ RNA isolated by hybridization/selection. The cDNA sequence contains a single open reading frame of 1317 nucleotides which encodes a polypeptide of 439 amino acids. The amino acid sequence deduced from the cDNA insert contains two copies of the 11-amino acid sequence Val-Glu-Phe-Tyr-Ala-Pro-Trp-Cys-Gly-His-Cys. Duplicate copies of this sequence also occur in the active site of rat and human protein disulphide isomerase (also known as the beta-subunit of human prolyl 4-hydroxylase, tri iodothyronine-binding protein) and in Form I phosphoinositide-specific phospholipase C, indicating that P5 falls into this newly defined superfamily of proteins. Genomic sequences similar to the cDNA clone are amplified 10-20-fold in hamster cells selected for resistance to increasing concentrations of hydroxyurea, a phenomenon observed earlier with cDNA clones for the M2 subunit of ribonucleotide reductase and ornithine decarboxylase. RNA blots probed with P5 cDNA show two poly(A)+ RNA species which are elevated in hydroxyurea-resistant cells. PMID- 1311172 TI - Structural gene and complete amino acid sequence of Vibrio alginolyticus collagenase. AB - The DNA encoding the collagenase of Vibrio alginolyticus was cloned, and its complete nucleotide sequence was determined. When the cloned gene was ligated to pUC18, the Escherichia coli expression vector, bacteria carrying the gene exhibited both collagenase antigen and collagenase activity. The open reading frame from the ATG initiation codon was 2442 bp in length for the collagenase structural gene. The amino acid sequence, deduced from the nucleotide sequence, revealed that the mature collagenase consists of 739 amino acids with an Mr of 81875. The amino acid sequences of 20 polypeptide fragments were completely identical with the deduced amino acid sequences of the collagenase gene. The amino acid composition predicted from the DNA sequence was similar to the chemically determined composition of purified collagenase reported previously. The analyses of both the DNA and amino acid sequences of the collagenase gene were rigorously performed, but we could not detect any significant sequence similarity to other collagenases. PMID- 1311173 TI - The interplay of temperature and protons in the modulation of oxygen binding by squid blood. AB - An extensive set of data relating to the binding of oxygen by haemocyanin from the squid Todarodes sagittatus has been collected under various experimental conditions. The results obtained show that, within the range of physiological pH, the concentration of protons affects mainly the high-affinity state of the molecule without significantly affecting the low-affinity state. As far as the effect of temperature is concerned, the data show a characteristic feature which is very similar to that previously described in the case of haemoglobins from Arctic mammals such as reindeer (Rangifer tarandus) and musk ox. (Ovibos moschatus). The shape of the oxygen equilibrium curve shows strong temperature dependence, since the overall heat of the binding of oxygen to the low-affinity state of the molecule is strongly exothermic and that to the high-affinity state is very close to zero. The results provide an outline of the intramolecular compromise that, through the interplay of temperature and protons, optimizes the loading and unloading of oxygen under the various environmental conditions experienced by this species of squid. PMID- 1311175 TI - Kinetics of superoxide scavenging by dismutase enzymes and manganese mimics determined by electron spin resonance. AB - This study presents an e.s.r. assay for superoxide dismutase (SOD). Enzymic reactions were studied in which Cu,Zn-SOD, Mn-SOD and Fe-SOD each competed with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) for superoxide anion (O2-) at pH 7.8 O2- from dissolved KO2 (potassium superoxide) in dimethyl sulphoxide was added directly to the enzyme solutions containing DMPO. The results show that, in this competition reaction system, the kinetics of the reactions between the enzymes and O2- follow a function y = f[( SOD]0.5). The rate constant, kSOD = 6.4 x 10(9) M-1. S-1, determined for Cu,Zn-SOD is approximately an order of magnitude larger than those for Mn-SOD and Fe-SOD. A comparative study of reported SOD mimics, including Mn2+, MnO2-desferrioxamine mesylate (Desferal) and MnO2-Desferal-ascorbate, was done. The results show that solutions of these complexes are approximately three orders of magnitude less active than Cu,Zn-SOD and approximately two orders of magnitude less active than Mn-SOD or Fe-SOD. The results also suggest that the reactivity toward O2- in solutions of these complexes originates from the Mn2+ present and not from the MnO2-Desferal complexes. PMID- 1311174 TI - The role of diacylglycerol in the exocytosis of the sperm acrosome. Studies using diacylglycerol lipase and diacylglycerol kinase inhibitors and exogenous diacylglycerols. AB - When ram spermatozoa were treated with Ca2+ and the ionophore A23187 to induce acrosomal exocytosis, a rise in diacylglycerol (DAG) mass was observed, concomitant with a rapid breakdown of [32P]P1-labelled phosphatidylinositol 4,5 bisphosphate and phosphatidylinositol 4-phosphate and a rise in [32P]Pi-labelled phosphatidate. Inclusion of the DAG lipase inhibitor RHC 80267 resulted in further but biphasic increases in DAG; there was an increasing accumulation of DAG with concentrations of RHC 80267 up to 10 microM, whereas higher concentrations produced lessening accumulation. Inclusion of RHC 80267 in the ionophore induction system also resulted in significant accelerations of the onset of exocytosis. In spermatozoa stimulated with Ca2+/A23187 and the DAG kinase inhibitor R59022, a similar increase in DAG levels together with stimulation of acrosomal exocytosis were observed. Preincubation of spermatozoa with sn-1-oleoyl-2-acetylglycerol, rac-1-oleoyl-2-acetylglycerol, sn-1,2 dioctanoylglycerol and sn-1,3-dioctanoylglycerol before treatment with Ca2+/A23187 resulted in a dose-dependent stimulation of exocytosis by all these isomers. Neomycin inhibited Ca2+/A23187-induced generation of DAG together with polyphosphoinositide breakdown, as well as acrosomal exocytosis. Inclusion of exogenous DAG, however, overcame the inhibitory effect of neomycin on exocytosis. Our results suggest that DAG has a key role in acrosomal exocytosis and that it acts as a messenger rather than as a substrate from which other active metabolites are generated. The lack of stereospecificity shown by the exogenous DAGs implies that DAG does not act by stimulating protein kinase C, but the metabolite's actual target in the sperm cell is as yet unclear. PMID- 1311176 TI - Inhibition of phosphatidylinositol 4-phosphate kinase by heparin. A possible mechanism for the antiproliferative effects of heparin. AB - Heparin and related glycosaminoglycans are important modulators of vascular smooth muscle cell growth, and may be involved in pathological processes such as atherosclerosis. Since polyphosphoinositide metabolism is a major mechanism for regulating cellular activities, including proliferation, the effects of glycosaminoglycans and polyanionic compounds on the activities of phosphoinositide kinases were characterized. Heparin and heparan sulphate caused dose-dependent inhibitions of rat brain cytosolic phosphatidylinositol 4 phosphate (PIP) kinase activity, with half-maximal inhibitory concentrations of approx. 0.5 and 5 microM respectively. PIP kinase was also inhibited by several dextran sulphates, but was not sensitive to inhibition by keratin sulphate, chondroitin sulphate or hyaluronic acid. Polynucleotides and acidic polypeptides were only weakly inhibitory. Heparin did not alter either the PIP- or the Mg(2+) dependence of PIP kinase. Addition of heparin to brain membranes suppressed PIP kinase activity without affecting phosphatidylinositol (PI) kinase activity. Heparin interfered with the ability of a GTP analogue to stimulate PIP kinase activity in these membranes, suggesting that it uncouples the kinase from an activating guanine-nucleotide-binding protein. In cultured A-10 vascular smooth muscle cells, heparin caused dose- and time-dependent inhibition of [3H]thymidine incorporation into DNA. Similar treatments with heparin decreased cellular levels of phosphatidylinositol 4,5-bisphosphate (PIP2) without changing PI and PIP levels. Therefore heparin-mediated inhibition of PIP kinase appears to lead to decreases in PIP2 levels which may attenuate cellular proliferation. PMID- 1311177 TI - Analysis of human hepatic microsomal glucose-6-phosphatase in clinical conditions where the T2 pyrophosphate/phosphate transport protein is absent. AB - The availability of a rare set of human hepatic microsomes in which T2, a pyrophosphate/phosphate transport protein of the glucose-6-phosphatase system, has been shown immunologically to be completely absent, has permitted further characterization of multicomponent glucose-6-phosphatase (EC 3.1.3.9). Pyrophosphatase activity in intact microsomes was found to be totally absent, but was normal in disrupted microsomes. However, Pi did not accumulate within the lumen of the microsomes when glucose 6-phosphate was the substrate. This was not as predicted if there is only one transport protein in the endoplasmic reticulum capable of transporting Pi, produced by glucose-6-phosphatase, out of the lumen. The results suggest that the pyrophosphate/phosphate transport system of human hepatic endoplasmic reticulum must be more complex than previously thought, as it must comprise at least two protein components. PMID- 1311179 TI - AIDS, health care workers, and the law. PMID- 1311178 TI - Basic calcium phosphate crystals stimulate cell proliferation and collagenase message accumulation in cultured adult articular chondrocytes. AB - OBJECTIVE: To investigate BCP (basic calcium phosphate) crystal-stimulated mitogenesis and collagenase gene transcription in primary cultures of porcine chondrocytes. METHODS: The role of protein kinases in BCP crystal-stimulated DNA synthesis was investigated using thymidine incorporation, kinase inhibitors, and protein kinase C (PKC) assays. Northern blot analysis was used to determine the levels of collagenase c-fos and c-jun message. RESULTS: BCP crystals stimulated chondrocyte proliferation in a PKC-dependent manner. Increased levels of collagenase message were preceded by an increased accumulation of c-fos, but not c-jun. CONCLUSION: BCP crystals could contribute to the abnormal chondrocyte proliferation and collagenase secretion observed in some rheumatic diseases. PMID- 1311180 TI - Characterization of the subunits and sugar moiety of human placental and leukemic beta-glucuronidase. AB - beta-Glucuronidase purified from human placenta and chronic myelogenous leukemic cells was composed of three components of 18, 64 and 80 kDa, though the relative contents of the components were different between the sources. Analysis of their N-terminal amino-acid sequences showed that the 18-kDa and 64-kDa components were derived from the 80-kDa component by cleavage between Val159 and Gly160. Furthermore, the enzyme was found to be glycosylated at Asn173 and Asn420 with high mannose-type oligosaccharides, based on the electrophoretic mobility of the components as well as the endopeptidic peptides before and after endoglycosidase treatment. The enzyme purified from leukemic cells was poorly phosphorylated by N acetylglucosamine 1-phosphotransferase as compared to the placental enzyme. PMID- 1311181 TI - Peripheral noradrenergic function during chronic lithium treatment in the rat. AB - Noradrenergic function was evaluated in the rat vas deferens following chronic treatment with lithium (30 mM in the diet for 2 weeks followed by 50 mM for 1 week). No alteration could be detected in: a) 3H-noradrenaline release evoked by electrical field stimulation, b) alpha 1-adrenoceptor function as assessed by contractile response to noradrenaline, c) active neuronal uptake of 3H noradrenaline, d) alpha 2-adrenoceptor activity, as assessed by yohimbine enhancement of evoked release of 3H-noradrenaline. The data argue against a primary action of lithium on the noradrenergic nerve. On the other hand, these findings do not rule out the possibility that the function of CNS noradrenergic neurons could be altered as a result of the known effects of lithium on the phosphatidyl-inositol system, and the greater sensitivity of CNS neurons to depletion of the neuronal membrane inositol pool. PMID- 1311182 TI - Murine monoclonal antibodies against pneumococcal capsular polysaccharide types 4, 8, 22F and 19A/19F. AB - Monoclonal antibodies (MAbs) were produced against pneumococcal capsular polysaccharides after subcutaneous immunization of BALB/c mice with a 23-valent vaccine (Pneumovax N, Merck, Sharp & Dohme). Selected antibodies were tested in ELISA against individual polysaccharides from 23 different pneumococcal types and in a dot blot assay with heat-killed whole bacteria adhered to nitrocellulose paper. Three MAbs (isotype IgM) were found to be specific for types 4, 8 and 22F, respectively, whereas one (isotype IgA) reacted both with 19A and 19F. Very mild acid hydrolysis of the capsular polysaccharides resulted in loss of reaction with the antibodies. PMID- 1311183 TI - New evidence that fiber from wheat bran can help reduce the risk for cancers of the breast and colon. PMID- 1311184 TI - Studies show new macrolide antibiotics to be superior to some older agents. PMID- 1311185 TI - Vesico-ureteric reflux in the damaged non-scarred kidney. AB - Renal damage without scarring is a rare manifestation of reflux nephropathy, and is infrequently reported in the literature. A retrospective review of a large series of patients with urinary tract disorders at the hospital for Sick Children, Great Ormond Street, identified 12 patients with vesico-ureteric reflux (VUR) with no evidence of scarring but with renal damage as assessed using technetium 99m dimercaptosuccinic acid (99mTc-DMSA) scan. There were 9 simplex kidneys, the differential function was between 33% and 43% (mean 38%). On follow up to date (mean 6.7 years) all kidneys show stable differential function with neither improvement nor deterioration. Only 8 children had a urinary tract infection. Renal damage without evidence of a focal scar associated with VUR may be a manifestation of growth arrest possibly due to glomerular damage. The sensitivity of 99mTc-DMSA may reveal the permanent nature of the renal damage. PMID- 1311186 TI - Urinary excretion of brush border antigens and other proteins in children with vesico-ureteric reflux. AB - This study was designed to evaluate the occurrence and the type of proteinuria in 82 children with vesico-ureteric reflux (VUR) with or without renal scars. The urinary excretion of the high molecular weight protein albumin was taken as an index of glomerular alterations and the excretion of retinol-binding protein (RBP), beta 2-microglobulin and brush border antigens (BBA) (measured by monoclonal antibody-based enzyme-linked immunosorbent assay) was taken as an index of tubular alterations. All such markers were increased in children with VUR and were related to the degree of renal function. Patients showing reduced creatinine clearance had very high levels of albuminuria, microproteinuria and BBA, with all these variables reciprocally correlated. In children with normal renal function however, only microproteins (not albumin or BBA) were slightly increased, thus indicating an isolated tubular defect without involvement of the proximal segment of the tubule. However, microprotein excretion did not correlate with the grade of scarring (99mtechnetium-dimercaptosuccinic acid scan), both RBP and beta 2-microglobulin excretion being normal in 75% of children with radioisotopic signs of renal lesions but increased in 17% of children without scars. Therefore, tubular proteinuria identifies different groups of children with VUR but is not related to renal scarring. Prospective studies will define the usefulness of proteinuria as a reliable indicator of renal outcome. PMID- 1311187 TI - Atrial natriuretic peptide and cyclic 3'5'-guanosine monophosphate as indicators of fluid volume overload in children with chronic renal failure. AB - Plasma atrial natriuretic peptide (ANP) and cyclic 3'5'-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n = 17, mean serum creatinine 371 +/- 242 mumol/l) and those with end-stage renal disease on haemodialysis (n = 18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0 +/- 0.4 vs 2.1 +/- 0.8 nmol/l, P less than 0.01), whereas plasma ANP was similar (26.9 +/- 9.7 vs 34.0 +/- 12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6 +/- 0.7 kg, corresponding to 4.5 +/- 2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r = 0.43, P less than 0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation. PMID- 1311189 TI - Plasminogen binding sites in normal human skin. AB - Plasminogen is detected in the basal cell layer of the epidermis, keratinocytes can generate plasminogen activators and it is suggested that the generation of plasmin may facilitate keratinocyte division, migration and differentiation. In this study we have investigated the characteristics of plasminogen binding sites in normal human epidermis. It was found that 6-aminohexanoic acid and benzamidine displaced endogenous epidermal plasminogen from the basal layer suggesting that endogenous plasminogen binds initially via the kringle 5 aminohexyl (AH) site. Plasminogen binding sites in epidermis were further investigated by displacing endogenous plasminogen and incubating sections with exogenously added glu plasminogen, lys-plasminogen and plasmin or the isolated plasminogen fragments kringles 1-3, kringle 4 and kringle 5L. The results suggest that the uptake of plasminogen involves primary interaction with the kringle 5AH site and a secondary interaction with lysine binding sites of kringles 1-3. Cell binding is not dependent upon additional reactions of the plasmin active centre. PMID- 1311188 TI - Detection of HSV-specific DNA in biopsy tissue of patients with erythema multiforme by polymerase chain reaction. AB - Formalin-fixed paraffin-embedded skin biopsies of lesions of erythema multiforme (EM) from 32 patients and 13 controls were examined for the presence of herpes simplex virus (HSV) by polymerase chain reaction (PCR) and for histological findings by direct immunofluorescence and staining with haematoxylin and eosin. HSV-specific DNA was detected in 23 (72%) patients. A history of recurrent skin rash was present in 59% of the PCR-positive cases, while 55% had had suspected HSV infections. Only two PCR-positive specimens were found in patients without a history of recurrent rash and/or previous oral lesions. One biopsy was positive for HSV by conventional cell cultures. There was no significant difference in histology between HSV-related and HSV-negative cases of EM. In the 13 control specimens [bullous pemphigoid (3), dermatitis herpetiformis (2), lichen planus (1), aphthous ulcer (1), fixed-drug eruption (1), varicella-zoster (1), hypereosinophilic syndrome (1), photocontact dermatitis (1), contact dermatitis (1), and cellulitis (1)], no HSV-DNA was detected. PMID- 1311190 TI - Cancer family syndrome associated with multiple malignant melanomas and a malignant fibrous histiocytoma. AB - A 64-year-old female with the cancer family syndrome suffered from multiple malignant melanomas and a malignant fibrous histiocytoma. She has shown unusually long survival which is a feature of these patients. PMID- 1311191 TI - Effects of staurosporine, PMA and A23187 on human melanocyte cultures with dibutyryl cyclic AMP. AB - Staurosporine, a protein kinase (PK) inhibitor, phorbol-12-myristate-13-acetate (PMA), a PKC activator and A23187 calcium ionophore were added to human melanocyte cultures with or without dibutyryl cyclic AMP (dbcAMP). After 2 days' incubation, changes in various melanogenic factors were examined such as tyrosinase activity and the amount of tyrosinase-related protein (TRP) as well as the morphology of the melanocytes. dbcAMP stimulated all the melanogenic factors. Staurosporine increased tyrosinase activity and amount of TRP and caused morphological changes with the formation of numerous dendrites, regardless of the presence of dbcAMP. In contrast, PMA did not significantly affect tyrosinase activity, TRP content or dendrite formation, with or without dbcAMP. The effects of staurosporine on tyrosinase activity and TRP content were completely inhibited by PMA, but PMA did not significantly affect the staurosporine-induced morphological changes. A23187 inhibited both tyrosinase activity and TRP content, regardless of the presence of dbcAMP, but did not affect the morphology of melanocytes. These findings suggest that tyrosinase activity and TRP content are regulated by adenylate cyclase and Ca2+ and partly by PKC, while the morphological features of melanocytes are affected by intracellular cAMP accumulation and by the inhibition of PKC. PMID- 1311192 TI - Generalized eruptive histiocytoma. AB - The case is reported of a 56-year-old female who over 18 months developed a symmetrical eruption of hundreds of bluish-red papules, a small number of which have spontaneously resolved. The clinical and histopathological findings were compatible with the diagnosis of generalized eruptive histiocytoma. The ultrastructural findings in this case suggest that this condition which is in the non-X group of histiocytic disorders is closely related to histiocytosis X. PMID- 1311193 TI - The molecular biology of retinoic acid receptors: orphan from good family seeks home. AB - A variety of c-DNAs coding for nuclear retinoic acid receptors (RARs) have recently been cloned. These receptors are members of the steroid/thyroid receptor superfamily and are believed to act as ligand-inducible transactivating factors; retinoic acid induces changes in receptor configuration that allows DNA binding and increased gene transcription from specific genes to occur. The retinoic acid receptor family itself may consist of up to 20 separate receptors each with a specific distribution and ligand binding characteristics. The RAR-gamma in the adult is found almost exclusively in the skin but other receptors which are found in a variety of other tissues are also present in skin. Associations of cutaneous disease states with receptor mutants have not yet been reported although some cases of leukaemia may be secondary to retinoic acid receptor gene rearrangements. A variety of approaches to identify the biological function of these receptors based on recombinant DNA technology are already underway. PMID- 1311194 TI - Analysis of African Burkitt's and high-grade B cell non-Burkitt's lymphoma for Epstein-Barr virus genomes using in situ hybridization. AB - We investigated the association of Epstein-Barr virus (EBV) with African cases of Burkitt's lymphoma (BL) and high grade B cell non-Burkitt's lymphoma (non-BL) occurring in areas where BL is endemic. The presence of EBV genomes was analysed in 24 cases using in situ hybridization with a 35S-labelled EBV probe applied to paraffin sections. EBV DNA was detected in each of 10 cases of BL in which technically satisfactory results were obtained, the virus being homogeneously distributed in all identifiable tumour cells. Two other cases of BL could not be evaluated because of technical problems. In contrast, EBV DNA was not detected in any case of high-grade non-BL (10 centroblastic and two immunoblastic lymphomas). These results confirm previous reports of the strong association of EBV with endemic BL, but suggest that the virus is not important in the pathogenesis of other types of African high-grade B cell lymphoma from regions where BL is endemic. PMID- 1311195 TI - Central role of tumour necrosis factor, GM-CSF, and interleukin 1 in the pathogenesis of juvenile chronic myelogenous leukaemia. AB - In previous studies on patients with juvenile chronic myelogenous leukaemia (JCML), we found excessive proliferation of malignant monocyte-macrophage elements in the absence of exogenous growth factor, and impaired growth of normal haematopoietic progenitors. In the current study, six newly-diagnosed JCML patients were investigated to characterize the disease further. In co-cultures, JCML cell culture supernatant as well as patient plasma obtained at diagnosis produced a striking reduction in numbers of control marrow BFU-E, CFU-GM, CFU-Meg and CFU-GEMM colonies. Monoclonal anti-tumour necrosis factor alpha neutralizing antibodies (anti-TNF-alpha Ab) abolished these inhibitory properties. In sharp contrast, JCML supernatants exerted a marked growth-promoting effect on autologous JCML cells cultured in clonogenic assays. Anti-TNF-alpha Ab and anti granulocyte-macrophage colony-stimulating factor neutralizing antibodies (anti-GM CSF Ab) both reversed the stimulating effect. Recombinant GM-CSF and recombinant TNF alpha produced a profound increase in JCML colonies when tested individually and anti-GM-CSF Ab reversed the TNF-alpha effect. Expression studies of TNF-alpha and TNF-alpha receptor genes of cultured JCML cells demonstrated mRNAs for both. Further, TNF-alpha activity was assayed in a wide variety of cell culture supernatants and in normal and patients' plasma, and only the JCML specimens showed increased TNF-alpha values. Recombinant interleukin-1 alpha (IL-1 alpha) also stimulated JCML colony growth, but polyclonal anti-IL-1 neutralizing antibodies did not suppress JCML colony numbers nor did it reverse the effects of TNF-alpha or GM-CSF. The evidence indicated that the JCML monokine which inhibits normal haematopoiesis is TNF-alpha and that the endogenously-produced TNF-alpha and GM-CSF from JCML cells play an important role in the pathogenesis of the disease by acting as autocrine growth factors. IL-1 alpha also stimulates JCML cell proliferation as an accessory factor and augments the effect of GM-CSF, TNF alpha or both. PMID- 1311197 TI - An update of cancer mortality among chrysotile asbestos miners in Balangero, northern Italy. PMID- 1311196 TI - The role of an anti-myeloperoxidase antibody in the diagnosis and classification of acute leukaemia: a comparison with light and electron microscopy cytochemistry. AB - The enzyme myeloperoxidase (MPO) is the hallmark of the myeloid lineage. We have analysed the presence of MPO in blasts from 180 cases of acute leukaemia (103 acute myeloid leukaemia (AML) and 77 acute lymphoid leukaemia (ALL) by means of monoclonal antibodies anti-MPO and immunocytochemistry (alkaline phosphatase anti alkaline phosphatase method). The aim of the study was to investigate the specificity and sensitivity of this marker compared with MPO cytochemistry by light (LM) and electron microscopy (EM), and with the expression of myeloid antigens. Anti-MPO was positive (greater than 3% blasts) in all but one of the 90 AML positive by LM cytochemistry. Of 13 AML cases negative by MPO cytochemistry, six showed 3-10% blasts reactive with anti-MPO and were also positive with antibodies to CD13 and/or CD33. The presence of MPO was confirmed in four of these by EM. The overall positivity of anti-MPO in AML was 92%. Anti-MPO was negative in all but two ALL (6% and 8% positive blasts). The blasts in these two cases were also CD13, CD33 and MPO positive by EM; both were thus reclassified as biphenotypic. Another two ALL reinterpreted as biphenotypic were negative by MPO cytochemistry and anti-MPO but were MPO positive by EM and with CD13 and/or CD33. We conclude that anti-MPO is a sensitive and specific early marker of myeloid blasts and should be incorporated in the routine immunophenotyping of acute leukaemia. PMID- 1311198 TI - Okadaic acid--a valuable new tool for the study of signal transduction and cell cycle regulation? AB - Okadaic acid is beginning to find its way into laboratories that study cellular control of gene expression and proliferation. By virtue of its specific inhibitory effects on certain protein phosphatases it seems to be a powerful tool for the analysis of regulatory phosphorylation-dephosphorylation events. Here, some of the important new findings with the use of this drug are summarized, and a few potential drawbacks of its application discussed. PMID- 1311199 TI - Structural analysis of the operator binding domain of Tn10-encoded Tet repressor: a time-resolved fluorescence and anisotropy study. AB - An engineered Tn10-encoded Tet repressor, bearing a single Trp residue at position 43, in the putative alpha-helix-turn-alpha-helix motif of the operator binding domain, was studied by time-resolved fluorescence and anisotropy. Fluorescence intensity decay data suggested the existence of two classes of Trp 43, defined by different lifetimes. Analysis of anisotropy data were consistent with a model in which each class was defined by a different lifetime, rotational correlation time, and fluorescence emission maximum. The long-lifetime class had a red-shifted spectrum, similar to that of tryptophan zwitterion in water, and a short rotational correlation time. In contrast, the spectrum of the short lifetime class was blue-shifted 10 nm compared to that of the long-lifetime class. Its correlation time was similar to that of the protein, which showed that Trp in this class was entirely constrained. Trp in this latter class could not be quenched by iodide, whereas most of the long-lifetime class was easily accessible. Presence of disruptive agents, such as 1 M GuCl or 3 M KCl, did not alter markedly the lifetimes but increased the weight of the short-lifetime component. In the same time, the rotational correlation time of this component was dramatically reduced. Taken together, our data suggest that the long-lifetime class could correspond to the tryptophan residues exposed to solvent whereas the short-lifetime class would correspond to the tryptophan residues embedded inside the hydrophobic core holding the helix-turn-helix motif. Destabilization of hydrophobic interactions would lead to an increase in the weight of the latter class for entropic reasons. Analysis of the fluorescence parameters of Trp-43 could provide structural information on the operator binding domain of Tet repressor. PMID- 1311200 TI - Effects of ouabain on the rotational dynamics of renal Na,K-ATPase studied by saturation-transfer EPR. AB - The interaction of a nitroxide spin-labeled derivative of ouabain with sheep kidney Na,K-ATPase and the motional behavior of the ouabain spin label-Na,K ATPase complex have been studied by means of electron paramagnetic resonance (EPR) and saturation-transfer EPR (ST-EPR). Spin-labeled ouabain binds with high affinity to the Na,K-ATPase with concurrent inhibition of ATPase activity. Enzyme preparations retain 0.61 +/- 0.1 mol of bound ouabain spin label per mole of ATP dependent phosphorylation sites, even after repeated centrifugation and resuspension of the purified ATPase-containing membrane fragments. The conventional EPR spectrum of the ouabain spin label bound to the ATPase consists almost entirely (greater than 99%) of a broad resonance at 0 degrees C, characteristic of a tightly bound spin label which is strongly immobilized by the protein backbone. Saturation-transfer EPR measurements of the spin-labeled ATPase preparations yield effective correlation times for the bound labels significantly longer than 100 microseconds at 0 degrees C. Since the conventional EPR measurements of the ouabain spin-labeled Na,K-ATPase indicated the label was strongly immobilized, these rotational correlation times most likely represent the motion of the protein itself rather than the independent motion of mobile spin probes relative to a slower moving protein. Additional ST-EPR measurements of ouabain spin-labeled Na,K-ATPase (a) cross-linked with glutaraldehyde and (b) crystallized in two-dimensional arrays indicated that the observed rotational correlation times predominantly represented the motion of large Na,K-ATPase containing membrane fragments, as opposed to the motion of individual monomeric or dimeric polypeptides within the membrane fragment. The results suggest that the binding of spin-labeled ouabain to the ATPase induces the protein to form large aggregates, implying that cardiac glycoside induced enzyme aggregation may play a role in the mechanism of action of the cardiac glycosides in inhibiting the Na,K-ATPase. PMID- 1311201 TI - Structural elements of human parathyroid hormone and their possible relation to biological activities. AB - Human parathyroid hormone (hPTH) and several deletion analogues were examined for the presence of secondary structure using circular dichroism spectroscopy. The spectra of hPTH and the deletion analogues 8-84, 34-53, 53-84, 1-34, 13-34, 1-19, and 20-34, in neutral, aqueous buffer, gave no evidence for extensive secondary structure. An alpha-helical-like spectral contribution was found to arise from a region within peptide 13-34. This spectral contribution was speculated to arise from partial stability of a helix consisting of residues 17-29. Molecular dynamics simulations of peptide 1-34 suggested that this peptide tends to fold with a bend defined by residues 10-14, with the amino-terminal and carboxyl terminal residues tending to be in more extended forms and the other residues in helical-like conformations. The addition of trifluoroethanol promoted the formation of alpha-helix, mainly in the 1-34 region. The putative helix comprised of residues 17-29 was stabilized by the addition of 10-20% TFE, while a second putative helix proximal to the amino terminus, and comprised of residues 3-11, was stabilized by slightly higher concentrations of TFE. An amphiphilic sequence was identified within the 20-34 fragment. The development of alpha-helix on binding this fragment, and other analogues containing this sequence, to palmitoyloleoylphosphatidylserine vesicles provided experimental evidence for the potential role of this amphiphilic sequence in binding to membranes or to a membrane receptor. The relationships between these alpha-helical regions in 1-34, either potentiated by trifluoroethanol or lipid vesicles, are discussed in terms of different receptor-binding regions within hPTH. PMID- 1311202 TI - 1H NMR assignment and secondary structure of the cell adhesion type III module of fibronectin. AB - The secondary structure of the tenth type III module from human fibronectin has been determined using NMR. This type of module appears many times in a wide variety of proteins. The type III module described here contains an Arg-Gly-Asp sequence known to be involved in cell-cell adhesion. The module was expressed in yeast and characterized by amino acid sequencing and mass spectrometry. 2D and 3D NMR spectroscopy of 15N-labeled protein was used to perform sequence-specific assignment of the spectrum. The secondary structure was defined by patterns of nuclear Overhauser effects, 3JNH-alpha CH spin-spin coupling constants, and amide proton solvent exchange rates. The molecule consists of seven beta-strands in two antiparallel beta-sheets with an immunoglobulin-like fold similar to that predicted for homologous modules in the cytokine receptor super family [Bazan, J. F. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 6934-6938]. The Arg-Gly-Asp sequence is located on a loop between the beta-strands F and G. PMID- 1311203 TI - 14,15N, 13C, 57Fe, and 1,2H Q-band ENDOR study of Fe-S proteins with clusters that have endogenous sulfur ligands. AB - The benefits of performing ENDOR experiments at higher microwave frequency are demonstrated in a Q-band (35 GHz) ENDOR investigation of a number of proteins with [nFe-mS] clusters, n = 2, 3, 4. Each protein displays several resonances in the frequency range of 0-20 MHz. In all instances, features are seen near v approximately 13 and 8 MHz that can be assigned, respectively, to "distant ENDOR" from 13C in natural-abundance (1.1%) and from 14N (the delta m1 = +/- 2 transitions); the nuclei involved in this phenomenon are remote from and have negligible hyperfine couplings to the cluster. In addition, a number of proteins show local 13C ENDOR signals with resolved hyperfine interactions; these are assigned to the beta carbons of cysteines bound to the cluster [A(13C) approximately 1.0 MHz]. Five proteins show resolved, local delta m1 = +/- 2 ENDOR signals from 14N with an isotropic hyperfine coupling, 0.4 less than or equal to A(14N) less than or equal to 1.0, similar to those seen in ESEEM studies; these most likely are associated with N-H...S hydrogen bonds to the cluster. Anabaena ferredoxin further shows a signal corresponding to A(14N) approximately 4 MHz. Quadrupole coupling constants are derived for both local and distant 14N signals. The interpretation of the data is supported by studies on 15N- and 13C-enriched ferredoxin (Fd) from Anabaena 7120, where the 15N signals can be clearly correlated with the corresponding 14N signals and where the 13C signals are strongly enhanced. Thus, the observation of 14N delta m1 = +/- 2 signals at Q band provides a new technique for examining weak interactions with a cluster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311204 TI - Does pyrophosphate bind to the catalytic sites of mitochondrial F1-ATPase? AB - The interactions between the pyrophosphate (PPi) binding sites and the nucleotide binding sites on mitochondrial F1-ATPase have been investigated, using F1 preparations containing different numbers of catalytic and noncatalytic nucleotide-binding sites occupied by ligands. In all cases, the total number of moles of bound nucleotides and PPi per mole of F1 was less than or equal to six. F1 preparations containing either three or two filled noncatalytic sites and no filled catalytic sites (referred as F1[3,0] and F1[2,0]) were found to bind 3 mol of PPi/mol of F1. Tight binding of ADP-fluoroberyllate complexes to two of the catalytic sites of F1 converted the three heterogeneous PPi-binding sites into three homogeneous binding sites, each exhibiting the same affinity for PPi. The addition of PPi at saturating concentrations to F1 containing GDP bound to two catalytic sites (F1[2,2]) resulted in the release of 1 mol of GDP. Furthermore, the addition of PPi to F1 filled with ADP-fluoroberyllate at the catalytic sites resulted in the release of 1 mol of tightly bound ADP/mol of F1. Taken together, these results indicate that PPi binds to specific sites that interact with both the catalytic and the noncatalytic nucleotide-binding sites of F1. PMID- 1311205 TI - Oxygen-evolving photosystem II preparation from wild type and photosystem II mutants of Synechocystis sp. PCC 6803. AB - We present here a simple and rapid method which allows relatively large quantities of oxygen-evolving photosystem II- (PS-II-) enriched particles to be obtained from wild-type and mutants of the cyanobacterium Synechocystis 6803. This method is based on that of Burnap et al. [Burnap, R., Koike, H., Sotiropoulou, G., Sherman, L. A., & Inoue, Y. (1989) Photosynth. Res. 22, 123 130] but is modified so that the whole preparation, from cells to PS-II particles, is achieved in 10 h and involves only one purification step. The purified preparation exhibits a 5-6-fold increase of O2-evolution activity on a chlorophyll basis over the thylakoids. The ratio of PS-I to PS-II is about 0.14:1 in the preparation. The secondary quinone electron acceptor, QB, is present in this preparation as demonstrated by thermoluminescence studies. These PS-II particles are well-suited to spectroscopic studies as demonstrated by the range of EPR signals arising from components of PS-II that are easily detectable. Among the EPR signals presented are those from a formal S3-state, attributed to an oxidized amino acid interacting magnetically with the Mn complex in Ca(2+) deficient PS-II particles, and from S2 modified by the replacement of Ca2+ by Sr2+. Neither of these signals has been previously reported in cyanobacteria. Their detection under these conditions indicates a similar lesion caused by Ca2+ depletion in both plants and cyanobacteria. The protocol has also been applied to mutants which have site-specific changes in PS-II. Data are presented on mutants having changes on the electron donor (Y160F) and electron acceptor (G215W) side of the D2 polypeptide. PMID- 1311206 TI - Synthesis and biochemical characterization of the new sulfhydryl-reactive ATP analogue 8-thiocyano-ATP. Its interaction with Na,K-ATPase and kinases. AB - The synthesis of 8-thiocyano-ATP (CNS8-ATP) is described. At 37 degrees C the ATP analogue inactivates Na,K-ATPase, hexokinase, and pyruvate kinase. In all three cases, inactivation can be prevented by the addition of ATP, thus indicating that CNS8-ATP is recognized within the ATP binding site of the above enzymes. Incubation of the inactivated enzymes with dithiothreitol restores the catalytic activities. Therefore, it is likely that in these enzymes a mixed disulfide (E-S S8-ATP) is formed between a sulfhydryl in the ATP binding site (E-SH) and the ATP analogue: [formula: see text] From the pseudo-first-order inactivation kinetics, a KD = 2.7 microM with k2 = 0.142 min-1 is calculated for the hexokinase and a KD = 40 microM with k2 = 0.347 min-1 is calculated for the pyruvate kinase interactions with the ATP analogue. At 4 degrees C, Na,K-ATPase recognizes CNS8 ATP with a KD = 8.3 microM. At 37 degrees C, the enzyme becomes inactivated by the ATP analogue in a biphasic manner. Inactivation results in the incorporation of [alpha-32P]8-CNS8-ATP into the catalytic alpha-subunit of the enzyme. Limited tryptic digestion in the presence of 150 mM KCl results in the formation of a radioactive peptide of Mr = 56,000, known to bear the purine binding domain of Na,K-ATPase. The results described in this article verify CNS8-ATP as a sulfhydryl-reactive ATP analogue and characterize this new ATP analogue as a useful tool for structure/function studies on ATP-recognizing enzymes. PMID- 1311207 TI - Enhanced sensitivity to oxidative stress in Cu,ZnSOD depleted rat erythrocytes. AB - The effects on red blood cells of superoxide dismutase (Cu,ZnSOD) depletion, induced by feeding Wistar rats with a copper deficient diet, were investigated. SOD depleted red blood cells were more sensitive to peroxidation and to hemolysis than normal cells when exposed to tert-butylhydroperoxide (t-BOOH). Membranes isolated from SOD depleted cells showed a lower content of vitamin E and higher (Na+, K+) and Mg2+ ATPase activities. These results support the view that superoxide dismutase plays an important role in cellular oxidative metabolism. PMID- 1311208 TI - Footprinting of EcoRI endonuclease at high pressure. AB - Hydroxyl radicals generated by irradiation with gamma rays have been used to footprint EcoRI endonuclease with single base pair resolution at pressures up to 144 MPa. At atmospheric pressure (0.1 MPa) a 10 base pair footprint was found. With increasing pressure three types of responses were observed: (1) bases distant from the recognition sequence showed a moderate increase in solvent exposure; (2) the bases at the point of enzymatic activity showed a large increase in cleavage by the hydroxyl radicals; and (3) the two center-most bases exhibited no pressure-induced change in solvent accessibility. The results are interpreted in terms of localized conformational changes of EcoRI. PMID- 1311209 TI - Expression of insulin-like growth factor-I (IGF-I) and its receptor in the peri implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone. AB - This study describes the expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) genes in the mouse uterus during the peri-implantation period (Days 1-6 of pregnancy), as well as effects of estradiol (E) and progesterone (P) on cell-specific IGF-I gene expression in the uterus of the ovariectomized adult mouse. Northern blot analysis showed that IGF-I mRNA levels were low but readily detectable in the uterus on Day 1 of pregnancy and steadily increased, reaching high levels just before (Day 4) and after initiation of implantation (Days 5 and 6). In general, IGF-IR transcripts were present in low abundance in uterine RNA throughout the peri-implantation period. However, six sizes of uterine IGF-IR transcripts were detected, and the relative abundance of two of these transcripts varied significantly during the peri-implantation period. Cell-specific expression of the IGF-I gene was examined by in situ hybridization to mRNA and immunohistochemical detection of protein. The results indicated that the synthesis of IGF-I on Days 1 and 2 was most predominant in glandular and luminal epithelial cells. However, on Days 3 and 4, stromal cells, and on Days 5 and 6, decidual cells appeared to be the predominant sites of synthesis of this growth factor. Uterine IGF-I gene expression was stimulated by ovarian steroids. Northern blot analysis showed that IGF-I transcripts were rare in the ovariectomized adult mouse uterus, but an injection of P and/or E caused a rapid accumulation of these transcripts. Analysis of the cell-specific expression of uterine IGF-I showed that E induced IGF-I gene expression primarily in epithelial cells, whereas P did so in the stroma. Superimposition of E on the P primed uterus further stimulated IGF-I expression in the stroma. The results of these studies are consistent with an autocrine/paracrine function of uterine IGF I, and indicate that ovarian steroids regulate the cell-specific and temporal patterns of expression of this gene in the peri-implantation mouse uterus. PMID- 1311210 TI - Gelatinase and proteoglycanase activity during the periovulatory period in the rat. AB - Gelatinase and proteoglycanase are metalloproteinases that govern extracellular matrix remodeling. In the present study, immature rats were primed with eCG (20 IU) and hCG (10 IU). Ovarian gelatinase and proteoglycanase activity were determined at the time of hCG administration (0 h) as well as 4, 8, and 12 h later. Gelatinase and proteoglycanase were extracted by homogenization in Triton and by heating (i.e., heat extraction). An aliquot of the heat extract was reduced and alkylated to destroy metalloproteinase inhibitors. Heat extracts not reduced and alkylated showed low levels of gelatinase and proteoglycanase activity that did not change at the different time points. However, with reduction and alkylation, gelatinolysis increased approximately 4-fold (p less than 0.05) at 4 h, 8 h, and 12 h after hCG priming. Proteoglycanase activity increased approximately 2-fold (p less than 0.05) between 0 and 8 h and declined at 12 h after hCG. The ovarian gelatinolytic activity was due to a metalloproteinase as demonstrated by the inhibition of enzyme activity by phenanthroline and EDTA (97.1 +/- 0.7% and 97.4 +/- 0.6% inhibition respectively). Proteoglycanase activity was not inhibited by phenanthroline (11.5 +/- 3.5%), suggesting that the enzyme activity was not specifically a metal dependent enzyme. Gelatin gel zymography of the ovarian extracts demonstrated four predominant and distinct gelatin-degrading enzymes of 78, 72, 66, and 62 kDa, similar to the size of gelatinase. The present findings demonstrate a periovulatory increase in ovarian gelatinolytic and proteglycanase activity that may play a pivotal role in connective tissue remodeling associated with ovulation. PMID- 1311211 TI - Etiology of primary liver cancer and the role of steroidal hormones. PMID- 1311212 TI - Reproductive factors in the etiology of hepatocellular carcinoma. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. AB - Data from a hospital-based case-control study conducted in four developing countries were analyzed to evaluate the role of reproductive factors in the etiology of liver cancer. Eighty-three patients newly diagnosed with primary liver cancer and 596 matched controls between the ages of 15 and 56 years completed study interviews. The relative risk of hepatocellular carcinoma was elevated significantly in women of high gravidity, an association that was attributable to the effects of full-term pregnancies. The adjusted relative-risk estimate in women who had ever had a full-term pregnancy was 1.6 (95 percent confidence interval = 0.6-4.1), and risk increased directly with the number of full-term pregnancies (P for trend = 0.03), rising to 3.8 among women with seven or more births compared to women with one to two births. Induced abortions and a history of miscarriage were unrelated to risk. These findings were unchanged after adjustment for a history of jaundice, lifetime number of sexual partners, or age at first sexual intercourse--variables which may be related to hepatitis B virus (HBV) exposure. Serum samples to determine HBV status were not collected, however, and it is not known whether the observed associations are independent of prior HBV infection. PMID- 1311213 TI - Histogenetic correlations between subcategories of small noncleaved cell lymphomas. AB - To assess the biologic relevance of the morphologic distinctions between subtypes of small noncleaved cell lymphomas (SNCL), ie, the sporadic Burkitt's type (sBT) and the non-Burkitt's type (nBT), we have examined the molecular organization of several lymphomagenic oncogenes (c-myc, bcl-1, bcl-2) and the potential pathogenetic contribution of the Epstein-Barr virus (EBV). Twenty-nine cases of SNCL, not associated with immunodeficiency syndromes, were reviewed and classified as sBT (18 cases) or nBT (11 cases) without knowledge of the clinical or molecular data. Southern blot analysis of 18 sBTs found 17 to contain c-myc rearrangements. Fifteen of these comigrated with an Ig heavy-chain gene segment, indicating t(8;14) translocation. Chromosome 8 breakpoints were clustered in the first exon and the first intron of the c-myc gene. Chromosome 14 breakpoints mapped to the JH locus in three tumors, the S mu locus in nine tumors, and the S alpha locus in the remaining three tumors. Cases involving the S alpha locus appeared to have a more rapid clinical course. All sBTs possessed germline bcl-2 and bcl-1 gene fragments. In contrast, Southern blot analysis of 11 nBTs found none with c-myc rearrangements. Rather, three of 10 evaluable nBTs had bcl-2 rearrangements. The remaining seven showed no evidence of involvement by any of the lymphoma-associated oncogene/breakpoint regions studied. EBV genome was detected in two sBTs and in one nBT, and thus was not a distinguishing feature. These results indicate that the subtle histologic differences that distinguish subcategories of SNCL are significant biologically and reflect distinct molecular mechanisms of lymphomagenesis. Furthermore, the data suggest that the nBTs comprise a heterogeneous group with respect to their molecular genetic composition and confirm the remarkable molecular genetic homogeneity of the sBT group. PMID- 1311214 TI - Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia. AB - The SCL gene, initially discovered at the site of a translocation breakpoint associated with the development of a stem cell leukemia, encodes a protein that contains the highly conserved basic helix-loop-helix (bHLH) motif found in a large array of eukaryotic transcription factors. Recently, we have described a nonrandom, site-specific SCL rearrangement in several T-cell acute lymphoblastic leukemia (ALL) cell lines that juxtaposes SCL with a distinct transcribed locus, SIL. The SIL/SCL rearrangement was found in leukemic blasts from 11 of 70 (16%) newly diagnosed T-cell ALL patients, a prevalence substantially higher than that of the t(11;14) translocation, which has previously been reported as the most frequent nonrandom chromosomal abnormality in T-cell ALL. We did not detect the SIL/SCL rearrangement in the leukemic blasts from 30 patients with B-cell precursor ALL, indicating that the rearrangement was specific for T-cell ALL. Analysis of RNA from these patients indicated that an SIL/SCL fusion mRNA was formed, joining SIL and SCL in a head-to-tail fashion. The fusion occurs in the 5' untranslated region (UTR) of both genes, preserving the SCL coding region. The net result of this rearrangement is that SCL mRNA expression becomes regulated by the SIL promoter, leading to inappropriate SCL expression. The resultant inappropriate expression of this putative transcription factor may then contribute to leukemic transformation in T-cell ALL. PMID- 1311215 TI - Reduced neuronal sensitivity to dieldrin and picrotoxinin in a cyclodiene resistant strain of Drosophila melanogaster (Meigen). AB - Toxicological and neurophysiological studies were performed to characterize the resistance mechanism in a cyclodiene-resistant strain of Drosophila melanogaster (Maryland strain). Dieldrin had an LC50 of 0.058 ppm against the larvae of susceptible D. melanogaster (Oregon-R wild type) when formulated in the rearing media. The LC50 of the resistant Maryland strain was 10.8 ppm, giving a resistance ratio (LC50-Maryland/LC50-susceptible) of 186-fold. Suction electrode recordings were made from peripheral nerves of the larval central nervous system to test whether reduced nerve sensitivity played any role in the observed resistance. In susceptible preparations (n = 5), inhibition of nerve firing by 1 mM gamma-aminobutyric acid (GABA) was effectively antagonized within 3-10 min by 10 microM dieldrin. In contrast, 30 min incubations with 10 microM dieldrin had no effect on preparations from cyclodiene-resistant individuals (n = 5). Similarly, 10 microM picrotoxinin blocked GABA-dependent inhibition in susceptible nerve preparations (n = 3). In recordings from resistant insects (n = 4), picrotoxinin displayed either weak antagonism of GABA or hyperexcitation indistinguishable from susceptible preparations. These results demonstrate that cyclodiene resistance in the Maryland strain of D. melanogaster 1) is expressed in immature stages, 2) is present at the level of the nerve, and 3) extends to picrotoxinin, albeit at a reduced level compared with dieldrin. The possible role of an altered GABA receptor in this resistance is discussed. PMID- 1311216 TI - Effect of endosulfan 35 EC on ATPases in the tissues of a freshwater field crab Barytelphusa guerini. PMID- 1311217 TI - Unusual hyperechoic appearance of prostate cancer on transrectal ultrasonography. AB - A series of 157 patients with prostate cancer underwent transrectal ultrasonography prior to radical prostatectomy. In 112 patients (71.3%) the tumours appeared hypoechoic relative to the echo pattern of the normal peripheral zone; in 43 (27.4%) they appeared isoechoic, and in only 2 (1.3%) did they appear purely or predominantly hyperechoic. These 2 hyperechoic tumours were unusual ductal adenocarcinomas with central necrosis and dystrophic calcification within solid tumour nests, a pattern similar to that of comedo-carcinoma of the breast. Calcification within prostate cancer was found in 4 of the 157 radical prostatectomy specimens, including 2 other hypoechoic cancers which contained intraluminal or psammomatous calcification. Although the most common sonographic appearance of localised prostate cancer is hypoechoic, a predominantly hyperechoic pattern is seen occasionally and suggests the presence of a high grade ductal adenocarcinoma. PMID- 1311218 TI - Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype. AB - Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histotype (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour specific" lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58 fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor alpha (TNF alpha) or interferon gamma, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR gamma/delta cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogenic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNF alpha and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor beta (TGF beta). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours. PMID- 1311219 TI - Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data. AB - Two patients presenting with malignant meningitis resulting from small-cell carcinoma of the lung and with lymphoblastic leukemia, respectively, were treated by intrathecal administration of etoposide. In both cases, this treatment was well tolerated and produced relief of the central nervous system symptoms. Pharmacokinetic data showed that cerebrospinal fluid drug levels of up to 5.2 micrograms/ml were achieved, which were considerably higher than those obtained after i.v. administration of high-dose etoposide. PMID- 1311220 TI - L- and T-type Ca2+ channels in canine cardiac Purkinje cells. Single-channel demonstration of L-type Ca2+ window current. AB - Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-type Ca2+ "window" current. We used the on-cell, patch-clamp technique to study Ca2+ channels from isolated cardiac Purkinje cells. Patches contained one or more Ca2+ channels 75% of the time. L-type channels were seen in 69% and T-type channels in 73% of these patches. With 110 mM Ba2+ as the charge carrier, the conductances of the L- and T-type Ca2+ channels were 24.2 +/- 0.8 pS (n = 9) and 9.0 +/- 0.5 pS (n = 8), respectively (mean +/- SEM). With 110 mM Ca2+ as the charge carrier, the conductance of the L-type Ca2+ channel decreased to 9.7 +/- 1.2 pS (n = 4), whereas the T-type Ca2+ channel conductance was unchanged. Voltage-dependent inactivation was shown for both L- and T-type Ca2+ channels, although for L-type Ca2+ channel with Ba2+ as the charge carrier, inactivation took at least 30 seconds at a potential of +40 mV. After channel inactivation was complete, L-type Ca2+ channel reopenings were observed following repolarizing steps into the window voltage range. Thus, our data identify both L- and T-type Ca2+ channels in cardiac Purkinje cells and demonstrate, at the single channel level, L-type channel transitions expected for a window current. Window current may play an important role in shaping the action potential and in arrhythmogenesis. PMID- 1311221 TI - P2-purinoceptor activation stimulates phosphoinositide hydrolysis and inhibits accumulation of cAMP in cultured ventricular myocytes. AB - Extracellular ATP modulates cardiac contraction through P2-purinoceptors on cardiac myocytes. To elucidate the molecular mechanism of this response, we examined the effects of P2-purinoceptor activation on phosphoinositide (PI) hydrolysis and the cAMP system in cultured ventricular myocytes of fetal mice. In a concentration-dependent manner, ATP stimulated accumulations of [3H]inositol monophosphate, bisphosphate, and trisphosphate with the half-maximum effective concentration of approximately 1 microM in the myocytes labeled with [3H]inositol. The order of efficacy of a series of adenyl compounds for stimulation of PI hydrolysis was adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), ATP greater than ADP, 5'-adenylylimidodiphosphate (APPNP) greater than alpha,beta-methyleneadenosine 5'-triphosphate (APCPP) greater than beta,gamma methyleneadenosine 5'-triphosphate, AMP greater than adenosine. On the other hand, 100 microM ATP gamma S inhibited isoproterenol-induced accumulation of cAMP by approximately 70% without decreasing the time to maximal cAMP levels, as measured by radioimmunoassay. This response was also concentration dependent, with a half-maximum inhibitory concentration (IC50) of approximately 1 microM. All of the tested ATP, ADP, and ATP analogues inhibited the cAMP system, and the responses to ATP gamma S, APPNP, and APCPP were insensitive to an A1-purinoceptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. Pertussis toxin attenuated the ATP-induced PI hydrolysis by no more than 25% at 100 ng/ml but completely suppressed the ATP gamma S-induced inhibition of the cAMP system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311223 TI - Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. AB - BACKGROUND: Experiments were performed in human ventricular myocytes to investigate properties of excitation-contraction coupling in patients with terminal heart failure. Myocytes were isolated from left ventricular myocardium of patients with cardiac failure caused by dilated or ischemic cardiomyopathy undergoing transplantation. These results were compared with those obtained from cells of healthy donor hearts that for technical reasons were not suitable for transplantation. METHODS AND RESULTS: [Ca2+]i transients and Ca2+ currents were recorded from isolated cells under voltage clamp perfused internally with the Ca2+ indicator fura 2. In cells that were stimulated externally, the cell permeant form of the indicator, fura 2-AM, was used. When action potentials were to be recorded, cells were stimulated in current clamp mode. Unstimulated Ca2+ current densities were not significantly different in myopathic and control cells. In diseased myocytes, resting [Ca2+]i levels were 165 +/- 61 nmol/l, compared with 95 +/- 47 nmol/l in normal cells. With 5 mmol/l Na+ in the pipette, peak [Ca2+]i transients were 367 +/- 109 and 746 +/- 249 nmol/l, respectively. The decline of [Ca2+]i during diastole was significantly slower in myopathic cells than in control cells. This was a result of a prolongation of the action potential and of a reduced Ca2+ sequestration by the sarcoplasmic reticulum. CONCLUSIONS: These results may partly explain the alterations of contractility in vivo in patients with heart failure. PMID- 1311222 TI - Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure. AB - The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle 1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure. PMID- 1311224 TI - Isolated presynaptic inotropic beta-adrenergic supersensitivity of the transplanted denervated human heart in vivo. AB - BACKGROUND: The regulation of contractility of the transplanted heart depends on circulating catecholamines resulting from cardiac denervation. Supersensitivity to circulating catecholamines may result from loss of presynaptic neuronal uptake or upregulation of postsynaptic beta-adrenergic receptors. METHODS AND RESULTS: Dose-response curves using the beta-adrenergic receptor agonists isoprenaline (no neuronal uptake) and epinephrine (neuronal uptake) were performed in vivo. The inotropic response was measured echocardiographically as the increase of fractional shortening (delta FS) and the increase of the systolic pressure/dimension ratio (delta P/D). The inotropic response to increasing doses of isoprenaline (5-20 ng/kg.min) was identical in 36 heart transplant recipients compared with 13 control subjects: delta FS during 20 ng/kg.min isoprenaline amounted to 18.2 +/- 6.2% versus 17.4 +/- 4.0% (NS) and delta P/D to 2.3 +/- 1.2 mm Hg/mm versus 2.2 +/- 0.5 mm Hg/mm (NS), respectively. A vagally mediated indirect negative inotropic effect in the innervated hearts was excluded by identical inotropic responses to isoprenaline in control subjects without and after atropine pretreatment. The inotropic response to increasing doses of epinephrine (10-40 ng/kg.min) was significantly augmented in 13 heart transplant recipients compared with 11 control subjects: delta FS during 40 ng/kg.min epinephrine amounted to 19.9 +/- 2.6% versus 8.6 +/- 2.0% (p less than 0.001) and delta P/D to 2.3 +/- 0.9 mm Hg/mm versus 0.6 +/- 0.3 mm Hg/mm (p less than 0.001), respectively. Pretreatment with desipramine (blockade of neuronal uptake) in control subjects resulted in a significantly increased inotropic response: delta FS during 40 ng/kg.min epinephrine amounted to 17.6 +/- 3.6% (p less than 0.001 versus untreated controls, NS versus heart transplant recipients) and delta P/D to 1.7 +/- 0.8 mm Hg/mm (p less than 0.001 versus untreated controls, NS versus heart transplant recipients). CONCLUSIONS: These findings provide evidence against a postsynaptic inotropic supersensitivity or subsensitivity of the beta adrenergic receptor-effector system of the transplanted denervated human heart in vivo. However, a marked presynaptic inotropic supersensitivity is present because of denervation-associated loss of neuronal catecholamine uptake. PMID- 1311226 TI - The scientific basis of cement versus cementless fixation. AB - The arguments for and against three implant materials (polymethylmethacrylate, cobalt-chrome alloy, and titanium aluminium vanadium alloy) when used as interfaces between a loaded implant and bone are reviewed from mechanical and biologic standpoints. It is concluded that there is neither an overwhelming advantage nor a disadvantage for any one of them. PMID- 1311225 TI - Integrin expression in human melanoma cells with differing invasive and metastatic properties. AB - During the process of tumor cell invasion and metastasis, tumor cells are known to interact with extracellular matrix proteins, endothelial cells, platelets and other organ-specific structures. Integrins are cell surface molecules which mediate cell-matrix and cell-cell interactions and are likely to be important for tumor cell survival and dissemination. The purpose of this study was to characterize the integrin and proteolytic enzyme repertoire from low (A375P), medium (A375M) and high metastatic (A375SM) human melanoma cell lines. These cell lines are also invasive through human amniotic membranes in vitro and their invasiveness parallels the reported metastatic phenotype. The types and levels of expression of the various integrin receptors were analysed by quantitative immunoprecipitation using a panel of monoclonal antibodies directed to known integrin subunits. In addition, cDNA probes to the integrin subunits were used in quantitative northern blot analysis. These data show that the integrin alpha v beta 3 increases 50- to 100-fold as these cells progress to a more metastatic phenotype. alpha 4 beta 1 levels also appeared to increase several fold, while other beta 1 integrins did not differ in their expression levels. The increased alpha v beta 3 expression in the more metastatic cells resulted in an increased adhesion to vitronectin and fibrinogen substrates in cell attachment assays. However, alpha v- and beta 3-specific antibodies did not inhibit A375 cell invasion through the amnion. Each cell line was found to release similar quantities of a 72-kDa gelatinase/type IV collagenase and tissue type plasminogen activator. These results suggest that during the progression of these tumor cells from a low to high metastatic phenotype, marked changes in integrin expression occurred which may facilitate interactions with platelets, endothelial cells and specific extracellular matrix proteins to promote metastasis. PMID- 1311227 TI - Glioblastoma: the past, the present, and the future. PMID- 1311228 TI - Spirits and spiritist therapy in southern Brazil: a case study of an innovative, syncretic healing group. AB - This paper examines the treatment of patients by a group of Spiritist healers in southern Brazil. After describing and analyzing a healing session, the practices are shown to be deviant from conventional Spiritism in two directions: (1) they employ a technique, called apometry, that they claim makes possible the transportation of a part of the patient's body to the astral world where it is treated by disincarnate doctors who do past life regressions; and (2) although a conventional Spiritist disobsession is performed, the healers invoke rival Afro Brazilian spirits who often are shown to have caused the patient's symptoms. Building on the work of Csordas (1983), I hypothesize that the discourse employed by the healers moves the patient to a new reality or phenomenological world in which s/he is healed "not in the sense of being restored to the state in which s/he existed prior to the onset of illness, but in the sense of being rhetorically 'moved' into a state dissimilar from both pre-illness and illness reality...(Csordas 1983:346)." The new state, in this case, is the world of Spiritism. Unlike the Catholic Pentecostals Csordas studied who already were members of a primary group of believers, however, the patients treated by the Brazilian healers are mostly unaffiliated individuals who face the increasing uncertainty and insecurity of life in disorganized, anomic, urban Brazil. By encompassing modern science on the one hand, and aspects of the Afro-Brazilian traditions on the other, this healing group appeals to the often distraught white middle and lower-middle classes, providing them with therapeutic meaning that in many cases leads to healing, conversion, and the sense of security and safety that often accompanies identifying with and belonging to a religious group. PMID- 1311229 TI - Direct effect of arachidonic acid on protein kinase C and LH-stimulated steroidogenesis in rat Leydig cells; evidence for tonic inhibitory control of steroidogenesis by protein kinase C. AB - The role of arachidonic acid in the regulation of steroidogenesis in rat Leydig cells was studied. A dose- and time-dependent biphasic effect on maximal and submaximal LH- and dibutyryl-cAMP-stimulated testosterone production was found. The locus of the inhibition, which occurred during 3 h incubation, was prior to the side chain cleavage of cholesterol and after cAMP production. The same inhibitory effect was found with the protein kinase C (PKC) activators, phorbol 12-myristate, 13-acetate (PMA) and oleic acid, also with no change in LH stimulated cAMP production. Arachidonic acid, PMA, and diolein, all stimulated PKC activity in a dose-dependent fashion in partially purified Leydig cell homogenates. When the cells were incubated for 5 h, arachidonic acid potentiated LH- and dibutyryl-cAMP-stimulated testosterone production. Similarly, incubation with PMA for 5 h, potentiated subsequent basal and dibutyryl-cAMP-stimulated testosterone production. PKC was down-regulated over 5 h (but not during 3 h) by pretreating Leydig cells with PMA or arachidonic acid in the presence of LH. Lipoxygenase and cyclooxygenase inhibitors did not alter the stimulatory effects of arachidonic acid. We conclude that the short-term inhibitory effect of arachidonic acid (and PMA) is via activation of PKC, but when protein kinase C (PKC) is down-regulated by these ligands, steroidogenesis is enhanced. These results suggest that steroidogenesis is normally under tonic inhibitory control by PKC. PMID- 1311230 TI - Chronic stimulation of the pituitary-adrenal axis in rats by interleukin-1 beta infusion: in vivo and in vitro studies. AB - It has been shown that acute administration of interleukin-1 (IL-1) to rats elicits a transitory increase in plasma ACTH and corticosterone (B) levels. To investigate the effects of chronic administration of IL-1 on plasma ACTH and B levels, in the present study rats were equipped with Alzet osmotic minipumps loaded with either IL-1 (delivery rate 0.5, 2.0, or 4.0 micrograms/24 h, ip, for 1 week) or saline. At the end of the treatment the rats were decapitated, the adrenals were weighed, and the in vitro release of beta-endorphin (beta E) by the anterior pituitary and that of B by the adrenal gland were measured. Continuous administration of 2.0 and 4.0 micrograms IL-1/24 h resulted in a persistent increase in plasma ACTH and B concentrations compared to the levels in saline infused rats, with peak levels on the first day of administration. In addition, adrenal weights of IL-1 rats were significantly higher than those of saline rats. The 4.0-micrograms IL-1/day in vivo treatment induced an increase in spontaneous in vitro secretion of beta E and B, while the in vitro responses of the pituitary (to CRF) and the adrenal (to ACTH) of animals treated in vivo with IL-1 were significantly diminished. IL-1 at a dose of 0.5 microgram failed to affect plasma ACTH and B values, adrenal weight, and in vitro beta E and B secretion. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at lower doses of IL-1 (2.0 and 0.5 micrograms), temperatures were elevated only on the first 2 days of infusion. IL-1 at doses of 2.0 and 4.0 micrograms/day induced suppression of body weight gain on the first 2 days of the treatment period compared to saline treatment. Plasma norepinephrine and/or epinephrine concentrations were raised only on day 1 of the 2.0- and 4.0-micrograms IL-1 experiments. Thus, the observed effects of IL-1 on the hypothalamo-pituitary adrenal axis probably do not result merely from stress induced by the treatment. Taken together, our data show the potential of IL-1 to induce a dose-dependent and long term activation of the pituitary-adrenal axis. PMID- 1311232 TI - Adrenocorticotropin increases interleukin-6 release from rat adrenal zona glomerulosa cells. AB - Interleukin-6 (IL-6) is produced by adrenal zona glomerulosa cells; its release is stimulated by several secretagogues, including IL-1 alpha, IL-1 beta, and angiotensin II. The present study reports that ACTH (0.1-100 nM) increased the release of IL-6 from primary cultures of rat adrenal cells in a concentration dependent manner. This increase was accompanied by an increase in cAMP content in cell extracts and in the incubation medium. The dynamics of IL-6 release from the adrenal cells also were investigated using a perifusion system; approximately 50 min were required for the effects of IL-1 alpha, IL-1 beta, and ACTH on IL-6 release to become apparent. Following withdrawal of the secretagogues, IL-6 release returned to basal levels within 90-120 min. In some experiments, the adrenal zona glomerulosa was separated from the zona fasciculata/reticularis to determine the origin of secretagogue-stimulated IL-6 release. PGE2 and forskolin increased IL-6 release from both cell types, but maximal release from zona glomerulosa cells was more than 10-fold greater than that from zona fasciculata/reticularis cells. ACTH (0.1-100 nM) increased intracellular cAMP levels in cells from both cell types in a concentration-dependent manner, but increased IL-6 release only from zona glomerulosa cells. Dexamethasone, an inhibitor of IL-6 production in several tissues, had no effect on either basal or stimulated IL-6 production in the adrenal. Because IL-1 beta is produced primarily by tissues of the immune system, whereas ACTH is a classical endocrine hormone, we investigated the effect of interaction of these proteins on IL-6 release from the adrenal. Together, IL-1 beta and ACTH stimulation of IL-6 release was greater than the sum of the effects of each substance separately; however, IL-1 beta did not potentiate the effect of ACTH on cAMP levels. Similarly, IL-1 beta potentiated IL-6 release stimulated by forskolin and (Bu)2cAMP. Thus, the adrenal may be an important convergence point between the immune and endocrine systems, and because IL-6 release is regulated by IL-1 alpha, IL-1 beta, ACTH, and angiotensin II, and this cytokine stimulates corticosterone release, IL-6 may play an important paracrine role in integrating the signals derived from these systems. PMID- 1311231 TI - Regulation of c-fos, c-jun and jun-B messenger ribonucleic acids by angiotensin II and corticotropin in ovine and bovine adrenocortical cells. AB - Previous work has shown that corticotropin (ACTH) and angiotensin-II (A-II), in addition to their acute steroidogenic effects, exert long-term influences on adrenal cell differentiated function, stimulatory or inhibitory, respectively. Certain nuclear proto-oncogenes have been implicated in the regulation of gene expression in many cell systems. We have investigated the effects of ACTH and A II on the levels of c-fos, c-jun, and jun-B messenger RNAs (mRNAs), in bovine and ovine (OAC) adrenal fasciculata cells. In both cell types ACTH produced time- (maximum at 1 h) and dose-dependent (ED50 congruent to 10(-12) M) increase in c fos (2- to 4-fold) and jun-B (10- to 20-fold) mRNA levels but did not affect c jun. The concentrations required to induce half-maximal mRNA accumulation and cortisol production were similar. A-II also produced a dose-dependent increase in c-fos and jun-B mRNAs but also in c-jun in both cell types, despite the fact that OAC are resistant to the steroidogenic action of the hormone. The stimulatory effects of A-II on c-fos mRNA were higher than those produced by ACTH, whereas the effects on jun-B were similar but ACTH abolished (OAC) or decreased (bovine adrenal fasciculata cells) the stimulatory effects of A-II on c-jun mRNA. The effects of ACTH and A-II on cortisol production and proto-oncogene mRNAs were in part mimicked by 8 Bromo-cAMP and the phorbol ester phorbol-12-myristate-13 acetate plus calcium ionophore A23187, respectively. In the presence of cycloheximide, which blocks the steroidogenic effects of both hormones, proto oncogene mRNAs were superinduced by both hormones. This result, together with the fact that dexamethasone failed to affect the mRNA levels suggests that the stimulatory effects of ACTH and A-II on proto-oncogene expression were not related to an autocrine/intracrine action of cortisol. Taken together, these findings show that the proto-oncogene mRNAs in normal adrenal cells are regulated by ACTH and A-II, acting through different intracellular pathways. They also demonstrate differential responsiveness of the Jun family to both hormones. Thus, the opposite long-term action of ACTH and A-II on adrenal cell differentiated function could be mediated by its different initial effects on proto-oncogene expression, in particular in the members of the Jun family. PMID- 1311233 TI - Protein kinase C activation by 12-O-tetradecanoylphorbol 13-acetate modulates messenger ribonucleic acid levels for two of the regulatory subunits of 3',5' cyclic adenosine monophosphate-dependent protein kinases (RII beta and RI alpha) via multiple and distinct mechanisms. AB - Messenger RNAs (mRNA) for two of the regulatory subunits of cAMP-dependent protein kinases (PKA), RII beta and RI alpha, are transiently (maximal levels at 6 h) stimulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) in cultured rat Sertoli cells in a time- and concentration-dependent manner. Whereas TPA (10(-7) M) stimulated RII beta mRNA 11 +/- 2.8 fold (mean +/- SEM), mRNA levels for RI alpha increased only 2.5 +/- 0.6-fold (mean +/- SEM). No effects of TPA on the other subunits of PKA (RII alpha, C alpha) were observed. TPA-dependent accumulation of mRNAs for RII beta and RI alpha was observed to the same extent in nucleus and cytoplasm. We have previously shown that mRNA levels for all the PKA subunits are increased by cAMP, particularly that of RII beta (greater than 50-fold). TPA modulated the stimulatory effects of cAMP on RII beta and RI alpha mRNAs in opposite directions. Whereas treatment with both 8-CPTcAMP and TPA gave an additive effect on RI alpha mRNA, TPA reduced the cAMP-dependent increase in RII beta mRNA. Although the mRNA for RII beta had returned to basal levels after 24 h of incubation with TPA, the presence of TPA still inhibited cAMP-dependent induction of mRNA for RII beta. In contrast, similar TPA treatment did not influence the subsequent cAMP-dependent stimulation of RI alpha mRNA. Preincubation with 8-CPTcAMP did not influence TPA-dependent stimulation of mRNAs for either RII beta or RI alpha. TPA induction of RII beta mRNA was completely blocked by cycloheximide (an inhibitor of protein synthesis), whereas that of RI alpha was not. The inhibitory effect of TPA on cAMP stimulation of RII beta mRNA was independent of ongoing protein synthesis. These results indicate that TPA induction of mRNAs for RI alpha and RII beta involves multiple and distinct mechanisms. The stimulatory effect of TPA on RI alpha mRNA levels and the inhibitory effect of TPA on cAMP-stimulated RII beta mRNA expression are probably mediated through stable factors, whereas proteins with rapid turnover or factors induced by TPA are involved in the stimulatory effect of TPA on RII beta mRNA. PMID- 1311234 TI - Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus. AB - We examined the effect of acute hypotensive hemorrhage on corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) messenger RNAs (mRNAs) in neurons of the rat hypothalamus. Sprague-Dawley male rats were cannulated (femoral artery and vein) and received a 15 ml/kg.3 min hemorrhage on the morning of the fourth day. Time controls received no hemorrhage. After light halothane anesthesia, the rats were decapitated at 1 or 4 h (six to nine rats per group). The hypothalami were removed, frozen, and sectioned at 12 microns. In situ hybridization was performed using two 48-base oligodeoxynucleotide probes for CRH and AVP message, respectively. Hemorrhage led to a fall in arterial blood pressure and heart rate that recovered by 1 h. Plasma ACTH, corticosterone, and AVP were elevated 20, 60, and 90 min after hemorrhage, but returned to near control levels by 4 h. CRH mRNA was significantly elevated 1 and 4 h after hemorrhage, as compared to time controls, in parvocellular neurons of the paraventricular nuclei. However, AVP mRNA was not different from controls at 1 or 4 h after hemorrhage in the magnocellular or parvocellular paraventricular nuclei, or in the supraoptic or accessory nuclei of the hypothalamus. AVP mRNA was also found in neurons of the suprachiasmatic nuclei, but there was no difference in the amount of mRNA between the 1-h hemorrhage and control groups. These data suggest that neural signals, originating for cardiovascular receptors activated by hemorrhage, up-regulate message for CRH but not for AVP in the paraventricular nuclei of the rat hypothalamus. PMID- 1311235 TI - Hormonal regulation of follicle-stimulating hormone receptor messenger ribonucleic acid levels in cultured rat granulosa cells. AB - The maturation of ovarian granulosa cells is dependent upon the pituitary gonadotropin FSH, the actions of which are mediated via specific plasma membrane receptors. To study the regulation of ovarian FSH receptor expression at the mRNA level, we used a specific cRNA probe to evaluate changes in FSH receptor transcripts in cultured granulosa cells. Granulosa cells obtained from immature estrogen-treated rats contained two predominant FSH receptor mRNA transcripts (7.0 and 2.5 kilobases), the levels of which declined in a time-related manner during a 2-day culture period. However, inclusion of FSH (30 ng/ml) in the culture medium prevented the decline in FSH receptor mRNA levels. Compared to controls, treatment of granulosa cells for 48 h with FSH (1-100 ng/ml) increased FSH receptor mRNA levels in a dose-dependent manner (ED50, 4.5 ng/ml), with a maximal 5.9 +/- 0.7-fold increase observed in response to 30 ng/ml FSH. The stimulatory actions of FSH were mimicked by the adenyl cyclase activator forskolin (0.1-30 microM), suggesting the involvement of cAMP in FSH receptor gene transcription and/or mRNA stability. Incubation of granulosa cells for 48 h with epidermal growth factor (EGF; 0.3-10 ng/ml), basic fibroblast growth factor (bFGF; 1-30 ng/ml), or insulin-like growth factor-I (IGF-I; 1-30 ng/ml) did not affect basal FSH receptor mRNA levels, whereas the highest doses of EGF and bFGF, but not IGF-I, completely suppressed the stimulatory effects of FSH (30 ng/ml) on its own receptor mRNA levels. Similarly, GnRH (10-1000 nM) attenuated the actions of FSH on its receptor mRNA levels in a dose-dependent manner (ID50, 8 nM). The inhibitory effects of GnRH (100 nM) were reversed by cotreatment with a GnRH antagonist ([Ac-D-Phe1,D-pCl-Phe2,D-Trp3,6]GnRH; 100 nM), indicating that the actions of GnRH are mediated via specific GnRH receptors. These data indicate that treatment of granulosa cells with FSH increases the levels of two FSH receptor mRNA transcripts. However, this positive feedback system, which may lead to an amplification of FSH action, is tightly regulated by the inhibitory actions of EGF, bFGF, and GnRH. Thus, the use of cultured rat granulosa cells provides a model system to analyze the hormonal regulation of FSH receptor gene expression in the ovary. PMID- 1311236 TI - Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. AB - To better understand the in vivo bone-inductive properties of recombinant human (rh) BMP-2, we examined the ability of the protein to alter the phenotype of a bone marrow stromal cell line. W-20-17. rhBMP-2 increased alkaline phosphatase activity in W-20-17 cells in a dose-responsive manner in the absence of an effect on proliferation. The induction of alkaline phosphatase activity was not apparent until 12 h after rhBMP-2 treatment had begun and was effectively eliminated by cotreatment with cycloheximide, suggesting a requirement for protein synthesis. Continued treatment of W-20-17 cells with rhBMP-2 for 8 days resulted in a significant increase, compared to control cultures, in the production of cellular cAMP in response to a PTH challenge. In addition, 4-day treatment with rhBMP-2 induced osteocalcin levels in W-20-17 cells. These results indicate that rhBMP-2 induces the expression of several markers associated with the osteoblast phenotype in W-20-17 cells and raises the possibility that BMP-2 may be involved in the differentiation of osteoblasts from progenitor cells resident in bone marrow. PMID- 1311237 TI - Beta-endorphin inhibits hypoglycemia-induced gene expression of corticotropin releasing factor in the rat hypothalamus. AB - Endogenous opioid peptides have a role in the regulation of the hypothalamic pituitary-adrenal axis. Recently, beta-endorphin (EP) has been thought to inhibit CRF release in vivo and in vitro. In the present study we examined the effects of central administration of EP on ACTH secretion and gene expression of both CRF in the hypothalamus and POMC in the anterior pituitary gland (AP) during basal and insulin-induced hypoglycemia in pentobarbital-anesthetized rats. Administration of EP in the lateral ventricle decreased basal CRF levels in the median eminence and inhibited basal and hypoglycemia-induced ACTH secretion in a dose-dependent manner. Hypoglycemia-induced POMC mRNA levels in the AP and CRF mRNA levels in the hypothalamus were also dose-dependently inhibited by the administration of EP. The inhibitory effect of EP was reversed by naloxone. These results suggest that 1) central administration of EP acts through the opioid receptor to inhibit hypoglycemia-induced CRF gene expression in the hypothalamus and CRF release, which results in a decrease in ACTH secretion and POMC mRNA levels in the AP; and 2) the active site of EP is the CRF neuron in the paraventricular nucleus. PMID- 1311238 TI - Stimulation of angiotensinogen production in primary cultures of rat hepatocytes by glucocorticoid, cyclic adenosine 3',5'-monophosphate, and interleukin-6. AB - The effects of hormones and cytokines on angiotensinogen production were studied in primary cultured rat hepatocytes. The basal secretion of angiotensinogen decreased during culture. The addition of dexamethasone and (Bu)2cAMP completely prevented this decrease. Angiotensinogen secretion by freshly plated hepatocytes was slightly increased in response to dexamethasone, but after 24 h in culture, hepatocytes no longer responded to dexamethasone alone. When hepatocytes were treated with (Bu)2cAMP, glucagon, or forskolin, angiotensinogen secretion increased in response to dexamethasone in a concentration-dependent manner. 17 beta-Estradiol and T3 failed to stimulate angiotensinogen secretion in either the presence or absence of (Bu)2cAMP. Interleukin-6 (IL-6) exhibited a stimulatory activity on angiotensinogen secretion, which was dependent on the presence of dexamethasone, whereas IL-1 and tumor necrosis factor had no effect in either the presence or absence of dexamethasone and/or (Bu)2cAMP. Unlike primary cultured hepatocytes, angiotensinogen secretion by rat hepatoma H4IIEC3 cells increased in response to dexamethasone alone. This increase was not enhanced by (Bu)2cAMP, but was enhanced by IL-6. Thus, in primary cultures of rat hepatocytes, neither glucocorticoid, cAMP, nor IL-6 alone stimulated angiotensinogen production, but a combination of glucocorticoid and cAMP or of glucocorticoid and IL-6 exhibited a stimulatory activity on angiotensinogen production. These results suggest that angiotensinogen production in the liver is synergistically regulated by these factors, whereas the hepatoma cell line H4IIEC3 lacks the regulatory mechanism of cAMP on glucocorticoid-induced angiotensinogen production. PMID- 1311239 TI - A specific, high affinity, saturable binding site for the 16-kilodalton fragment of prolactin on capillary endothelial cells. AB - A 16-kilodalton N-terminal fragment of PRL (16K PRL) is formed by enzymatic cleavage of intact 23-kilodalton PRL (23K PRL) in the pituitary gland and in target tissues for PRL. 16K PRL inhibits the growth of capillary endothelial cells, while intact PRL was inactive suggesting that 16K PRL acted via a receptor other than the PRL receptor. To analyze whether this inhibitory effect could be mediated through an specific 16K PRL receptor, we characterized the binding of 16K PRL to membrane preparations of bovine brain capillary endothelial (BBE) cells. 16K PRL was generated by the proteolysis of rat 23K PRL with a particulate fraction from rat mammary gland homogenates and purified by gel filtration. The specific binding of [125I]16K PRL to BBE cell membranes was high affinity (Kd = 9.9 nM), saturable (Bmax = 4.8 pmol/mg protein), and reversible. In competition studies for [125I]16K PRL binding, 16K PRL was most potent, while little displacement was observed with high concentrations of 23K PRLs, growth hormones, and basic fibroblast growth factor. Blockade of reformation of disulfide bonds by carbamidomethylation of 16K PRL, a procedure which increases the biological activity of the molecule, increased its binding affinity (Kd = 0.9 nM). Cross linking experiments identified a 52,000 and a 32,000 mol wt protein as the major 16K PRL binding species. These data demonstrate the presence of specific, high affinity, saturable binding sites for 16K PRL on BBE cell membranes and support biological findings that 16K PRL inhibits capillary endothelial cell proliferation, through a novel, high affinity receptor. PMID- 1311240 TI - Isolation and mode of action of rabbit corticostatic (antiadrenocorticotropin) peptides. AB - Corticostatic peptides are a family of arginine-rich cysteine-rich peptides that inhibit ACTH-stimulated corticosterone (B) production in rat adrenal cell suspensions. In this communication we describe a new method for the facile isolation and purification of these basic peptides from rabbit adult lung. We then describe the isolation and sequences of the four rabbit peptides, CSI, CSII, CSIII, and CSIV, and compare their biological activities in the ACTH (150 pg/ml) inhibition assay. CSI is by far the most potent of the four peptides. Using CSI as a model, we then studied its effects on the proximal and distal parts of the pathway leading to the generation of cAMP. CSI had no effect on (Bu)2cAMP action on forskolin or cholera toxin in their ability to mimic ACTH and increase B production in rat adrenal cells, nor did CSI have any effect on the stimulation of B production by pertussis toxin. Endogenous cAMP stimulated by ACTH decreased after the addition of CSI, which pointed to the inhibition of ACTH binding to explain the mode of action of this corticostatin. Displacement of the specific binding of labeled ACTH by CSI and the ACTH antagonist ACTH-(6-24) was determined, and indeed, CSI did displace ACTH from its binding site. The question of what portion of the ACTH molecule was involved in the action of CSI was answered by studying ACTH-(1-13) acetyl amide (alpha MSH) and ACTH-(1-18) amide. CSI had no effect on alpha MSH stimulation of B production, but did lower the production of B stimulated by ACTH-(1-18) amide. Therefore, CSI must act on ACTH (14-18), which is part of the so-called address region of ACTH, which is -Gly14 Lys15-Lys16-Arg17-Arg18-, the very basic part of the molecule. These results indicate that CSI acts by competing with ACTH for its binding receptor on the adrenal cell and that this competition is confined to amino acids 14-18 of the molecule when it is bound to the receptor. PMID- 1311242 TI - Insulin like growth factor-I induces limited association of phosphatidylinositol 3-kinase to its receptor. AB - Stimulation by insulin-like growth factor-I (IGF-I) of LISN C4 cells, a mouse fibroblast cell line that overexpresses human IGF-I receptors, led to an increase in the amount of a phosphatidylinositol kinase that could be immunoprecipitated by anti-IGF-I receptor or anti-phosphotyrosine antibodies. The identity of the lipid produced in phosphatidylinositol kinase assays of anti-IGF-I receptor or anti-phosphotyrosine immunoprecipitates indicated that IGF-I selectively increased the amount of immunoprecipitated phosphatidylinositol 3-kinase activity. The amount of immunoprecipitated phosphatidylinositol 3-kinase activity that was increased by IGF-I followed a time course that paralleled the stimulation of IGF-I receptor beta-subunit autophosphorylation. The amount of phosphatidylinositol 3-kinase activity detected in anti-IGF-I receptor immunoprecipitates represented only 2% of that which was immunoprecipitated by anti-phosphotyrosine antibody. Furthermore, phosphatidylinositol 3-kinase activity which was recovered with anti-phosphotyrosine antibody was present in both cytosol and particulate cell fractions at approximately similar levels. Taken together, these results suggest that the stimulation of the IGF-I receptor tyrosine kinase leads to an increase in the amount of phosphatidyl inositol 3 kinase activity immunoprecipitated by antiphosphotyrosine and anti-IGF-I receptor antibodies and to a limited association with the IGF-I receptor itself, even though these cells express very high levels of IGF-I receptors. That the majority of phosphatidylinositol 3-kinase activity does not tightly associate with the IGF I receptor after IGF-I stimulation suggests that it may be associated with other tyrosine phosphorylated proteins. Alternatively, the kinase itself may become phosphorylated on tyrosine and dissociate from the IGF-I receptor. In this manner, an increase of phosphatidylinositol 3-kinase activity by IGF-I deviates from the activation of phosphatidylinositol 3-kinase by platelet-derived growth factor receptor in that a tight association with the receptor is not produced after stimulation. PMID- 1311241 TI - Retinoic acid decreases nuclear triiodothyronine receptor expression and impairs an early step of adipose differentiation in the thyroid hormone-sensitive mouse Ob 17 preadipocyte cell line. AB - In the murine preadipocyte cell line Ob 17, T3 is known to be necessary at an early step of adipose differentiation for the expression of late phenotypes [lipogenic enzymes such as malic enzyme, glycerol-3-phosphate dehydrogenase (GPDH), etc.] and not necessary for the expression of lipoprotein lipase (LPL), which emerges earlier, at growth arrest. These cells contain nuclear T3 receptors, which mainly belong to products of the c-erbA alpha gene and are down regulated by T3. In this work, retinoic acid (RA) added to Ob 17 cells at growth arrest impaired morphological differentiation and the development of both late (malic enzyme and GPDH) and early (LPL) phenotypes regardless of whether T3 was added. T3 sensitized the cells to the inhibitory action of RA; the ED50 for GPDH activity was shifted from 0.5 microM to 3 nM in cells cultured with 1.5 nM T3. Later addition of RA (6 days after growth arrest) did not inhibit the differentiation. RA also brought out a marked and fast decrease in nuclear T3 receptors. This was observed whatever the stage of cell development and related to both a rapid decrease in the relative abundance of c-erbA alpha-related mRNA species and an increased disappearance rate, suggesting the involvement of pre- and posttranslational events. RA and T3 acted additively in decreasing the T3 receptor and c-erbA alpha mRNA levels. The effects of RA on T3 receptors were rapidly reversed after RA withdrawal; the reversal was large (75%) when RA was introduced at growth arrest and total when introduced later. The cell sensitivity to RA, considering the T3 receptors, was higher at growth arrest (ED50 for RA, 0.2 and 1.5 microM in assays with RA added at growth arrest and 5 days later, respectively). The results suggest intricated regulatory pathways between RA and T3 at an early step of adipose differentiation and also suggest that among different mechanisms through which RA may impair this differentiation, a decreased level of nuclear T3 receptors at an early period should play a role. PMID- 1311243 TI - Defects of insulin's signal transduction in old rat livers. AB - Aging is associated with a postbinding defect in insulin action, leading to increased glucose intolerance and occasional diabetes. To determine whether defects in insulin receptor kinase (IRK) activity or in the phosphorylation of its physiological substrates underlie this age-related phenomenon, young (2-3 months old) and old (24-27 months old) Wistar rats were studied. When assayed in vitro, the hepatic IRK activities of noninjected old and young rats were comparable. Thirty seconds after the injection of insulin, the hepatic IRK activity of young rats increased 7- to 10-fold in a dose-dependent manner, with maximal effects obtained in rats injected with 20 mg insulin. By contrast, old animals exhibited impaired in vivo activation, with a mean 50% reduction in maximal IRK activity. When the rats were grouped into animals with mild (20%), moderate (50%), and severe (80%) reductions in maximal IRK activity, it was found that the mild and moderate defects could be reversed once the receptors were subjected to extensive autophosphorylation in vitro. The severe form of the defect was essentially irreversible and could not be corrected by phosphorylation in vitro. Immunoblotting with anti P-Tyr antibodies revealed that the reduced IRK activity in the old animals correlated with reduced intrahepatic tyrosine phosphorylation of the beta-subunit of the insulin receptor and pp180, a putative substrate of IRK. We, therefore, conclude that glucose intolerance in aging could be attributed at least in part to acquired defects in the in vivo activation of the hepatic IRK, which results in reduced phosphorylation of its putative substrate pp180. PMID- 1311244 TI - Thyrotropin regulates autophosphorylation and kinase activity in both the insulin and the insulin-like growth factor-I receptors in FRTL5 cells. AB - TSH regulation of insulin and insulin-like growth factor-I (IGF-I) receptor kinases has been studied in FRTL5 cultured thyroid cells. Preincubation of intact cells with TSH increased by 2-fold insulin and IGF-I receptor autophosphorylation and phosphorylation of the p175 endogenous substrate for the receptors. Enhanced phosphorylations reached a maximum within 30 min, were maintained for 30 min more, and vanished after 120 min of TSH incubation. TSH dose-responses exhibited half-maximal and maximal effects at 1 and 10 pM, respectively. In vitro, insulin as well as IGF-I receptors purified from cells treated with 10 pM TSH also exhibited 2-fold enhanced receptor autophosphorylation and kinase activity toward the exogenous substrate poly(Glu,Tyr) (4:1). At variance with TSH, cell incubation with either 8-bromo-cAMP or the protein kinase-C activator 12-O tetradecanoylphorbol-13-acetate inhibited insulin and IGF-I receptor kinases. In intact cells, TSH stimulation of insulin and IGF-I receptor kinases was accompanied by enhanced turnover of phosphate on autophosphorylated receptors, increased receptor tyrosine phosphorylation, and decreased receptor serine/threonine phosphorylation in response to insulin. Incubation of in vivo labeled insulin and IGF-I receptors with extracts from TSH-treated cells also decreased receptor phosphoserine and phosphothreonine content. Furthermore, preincubation of insulin and IGF-I receptors with extracts from TSH-treated cells enhanced in vitro autophosphorylation. The latter effect was inhibited by the serine/threonine phosphatase inhibitors fluoride and okadaic acid, but not by the tyrosine phosphatase inhibitor vanadate. The data suggest that in FRTL5 cells, TSH induces the activity of a Ser/Thr protein phosphatase, which dephosphorylates insulin and IGF-I receptors and enhances their endogenous kinases. PMID- 1311245 TI - Angiotensin-II inhibits Na+/K+ pump in rat adrenal glomerulosa cells: possible contribution to stimulation of aldosterone production. AB - The control of Na+/K+ pump activity was studied in rat adrenal glomerulosa cells. Ninety percent of K+/86Rb accumulation was blocked by ouabain, and the dose response curve of inhibition by ouabain was monophasic (IC50, approximately 80 microM), suggesting the role of a single type of Na+/K+ pump (alpha-isoenzyme) in 86Rb accumulation by rat glomerulosa cells. The basal activity of the Na+/K+ pump was much higher in glomerulosa cells than in adrenal fasciculata cells or hepatocytes, as judged by the ouabain-sensitive uptake of 86Rb. In contrast to the two other cell types, increasing Na+ influx with the Na+ ionophore monensin failed to significantly affect ouabain-sensitive 86Rb uptake in glomerulosa cells, suggesting that in glomerulosa cells even the resting intracellular Na+ concentration is sufficient for maximal activity of the Na+/K+ pump. Angiotensin II (AII) inhibited the ouabain-sensitive 86Rb uptake by glomerulosa cells. The effect of AII was abolished by the selective antagonist of the AT1 type of AII receptors (DuP 753), while PD 123177, an AT2 antagonist was ineffective. AT1 receptors of glomerulosa cells coupled to phospholipase-C activation and, thus, to Ca2+ signal. The inhibitory effect of AII was dependent on the extracellular Ca2+ concentration, but an elevation of cytoplasmic Ca2+ by Ca2+ ionophore ionomycin failed to mimic the effect of AII. These data suggest that Ca2+ is required for but does not mediate the inhibitory effect of AII on the Na+/K+pump. Pharmacological activation of protein kinase-C by phorbol ester did not modify 86Rb accumulation by the cells. Ouabain induced a nifedipine-sensitive elevation in the cytoplasmic Ca2+ concentration and exerted a stimulatory effect on aldosterone production, suggesting participation of the inhibition of the Na+/K+ pump in the aldosterone stimulatory action of AII. PMID- 1311246 TI - Presence of epidermal growth factor, platelet-derived growth factor, and their receptors in human myometrial tissue and smooth muscle cells: their action in smooth muscle cells in vitro. AB - Immunohistochemical observations indicate that human myometrial smooth muscle cells express epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-AB and contain EGF and PDGF-beta receptors with no variation in intensity with phases of the menstrual cycle. Furthermore, immunofluorescent microscopic studies revealed that primary myometrial smooth muscle cell cultures also express EGF, PDGF-AB, and contain EGF and PDGF-beta, but not alpha-receptor. Incubation of subconfluent smooth muscle cells in serum-free medium leads to quiescence within 48 h as demonstrated by 3H-thymidine incorporation and labeling index. Exposure of quiescent cells to 10% fetal bovine serum stimulates resumption of DNA synthesis and proliferation in a time-dependent manner with a doubling time of 41.6 h. EGF (1.5-50 ng/ml) and PDGF-AB (1-10 ng/ml) in a dose- and time dependent manner significantly stimulated 3H-thymidine incorporation by quiescent myometrial smooth muscle cells (P less than 0.05). Combinations of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) significantly increased 3H-thymidine incorporation induced by either growth factor alone (P less than 0.05). PDGF-BB at 10 ng/ml also stimulated 3H-thymidine incorporation and its effect was similar to that induced by PDGF-AB at the same concentration. 17 beta-Estradiol (E2) at 1 microM inhibited 3H-thymidine incorporation by the smooth muscle cells (P less than 0.05). E2 also reduced the stimulatory effect of EGF (15 ng/ml) and PDGF (3 ng/ml). Progesterone at 1 microM either alone or in combination with E2 did not have any effect on 3H-thymidine incorporation or alter the mitogenic action of EGF and PDGF. The effect of EGF and PDGF on cell growth and 3H-thymidine incorporation by myometrial smooth muscle cells was independent of phases of the menstrual cycle. In summary, the results of present studies indicate that human myometrial tissue and myometrial smooth muscle cells in primary culture locally produce EGF and PDGF-AB and contain EGF and PDGF-beta, but not alpha-receptors. Moreover, the myometrial smooth muscle cells in culture respond to the mitogenic action of EGF and PDGF. PMID- 1311247 TI - Functional LH receptor appears in the neonatal rat ovary after changes in the alternative splicing pattern of the LH receptor mRNA. AB - The LH receptor (R) function, as assessed by ligand binding and stimulation of cAMP production, is initiated in the neonatal rat ovary around day 7 of life. To correlate this with the onset of expression of the LHR gene, we assessed the presence of the cognate mRNA in the developing rat ovary from day 17 of fetal life onwards using PCR multiplication of reverse transcribed LHR mRNA, followed by southern hybridization and sequencing of the PCR products. Our findings indicate that only truncated versions of LHR mRNA are present in the developing rat ovary as early as day 17 fetal life and up to day 7 post partum. Concomitant with the appearance of a functional LH receptor (after day 7 post partum), two larger LHR mRNA species (2.6 and 6.7 kb) appear, which are also present in the adult ovary. These findings indicate that the LHR gene is probably constitutively expressed in the developing rat ovary, and that the onset of translation of functional LH receptor occurs through a change in the alternative splicing pattern of LHR mRNA. PMID- 1311248 TI - Atriopeptin: an endogenous corticotropin-release inhibiting hormone. AB - Activation of the hypothalamic-pituitary-adrenocortical axis is a major component of the body's response to stress. Current theories on the pathophysiology of disorders associated with hyperfunction of the axis, such as depression and Cushing's stress, are based on the concept that anterior pituitary adrenocorticotropin (ACTH) secretion is stimulated by hypothalamic corticotropin releasing hormones and inhibited by adrenal corticosteroids. Hypothalamic inhibitory control of pituitary ACTH secretion has been also postulated, but has not gained general acceptance because of the lack of definitive evidence for a corticotropin-release inhibiting hormone. It is shown here that in conscious rats stress-induced secretion of ACTH and corticosterone is markedly enhanced by the immunoneutralisation of atriopeptin. Therefore, we propose that atriopeptin is a physiologically relevant corticotropin-release inhibiting hormone. PMID- 1311249 TI - Inhibition of endosomal proteolytic activity by leupeptin blocks surface expression of MHC class II molecules and their conversion to SDS resistance alpha beta heterodimers in endosomes. AB - The biosynthesis of MHC Class II molecules starts with the assembly of the alpha and beta subunits and the invariant chain. Intracellular transport of Class II molecules was followed in pulse-chase experiments of a human Epstein-Barr virus transformed B lymphoblastoid cell line. Entry of Class II molecules into the endocytotic pathway and their cell surface appearance were monitored using neuraminidase as a fluid endocytotic marker and as a surface probe, respectively. In the course of intracellular transport, the Class II associated invariant chain is removed by proteases located in the endosomal pathway. Here, we show that leupeptin inhibits not only invariant chain breakdown, but also surface deposition of newly synthesized Class II molecules. Class II molecules display remarkable resistance to SDS at ambient temperature when occupied by peptide. We exploit this property to show that peptide binding precedes surface expression, and takes place in the course of intracellular transport through an endosomal compartment. Leupeptin blocks the conversion of Class II molecules to an SDS resistant complex. PMID- 1311250 TI - Ubiquitin as a degradation signal. AB - For many short-lived eukaryotic proteins, conjugation to ubiquitin, yielding a multiubiquitin chain, is an obligatory pre-degradation step. The conjugated ubiquitin moieties function as a 'secondary' signal for degradation, in that their posttranslational coupling to a substrate protein is mediated by amino acid sequences of the substrate that act as a primary degradation signal. We report that the fusion protein ubiquitin--proline--beta-galactosidase (Ub-P-beta gal) is short-lived in the yeast Saccharomyces cerevisiae because its N-terminal ubiquitin moiety functions as an autonomous, primary degradation signal. This signal mediates the formation of a multiubiquitin chain linked to Lys48 of the N terminal ubiquitin in Ub-P-beta gal. The degradation of Ub-P-beta gal is shown to require Ubc4, one of at least seven ubiquitin-conjugating enzymes in S.cerevisiae. Our findings provide the first direct evidence that a monoubiquitin moiety can function as an autonomous degradation signal. This generally applicable, cis-acting signal can be used to manipulate the in vivo half-lives of specific intracellular proteins. PMID- 1311251 TI - PDGF alpha- and beta-receptors activate unique and common signal transduction pathways. AB - We have examined the signal transduction pathways of the PDGF alpha- and beta receptors, in order to characterize the specificity of each receptor type in the signaling. Porcine aortic endothelial cell lines expressing equal levels of either PDGF alpha- or beta-receptors were established. The alpha- and beta receptor cells responded mitogenically to stimulation with the proper PDGF isoforms. Three aspects of actin reorganization were examined after ligand stimulation: loss of stress fibres, appearance of edge ruffles and formation of circular membrane ruffles. The beta-receptor cells showed a response to ligand stimulation which included all three features. The alpha-receptor cells exhibited edge ruffles and loss of stress fibres, but circular ruffles could not be found in several independent alpha-receptor cell lines. The beta-receptor cells, but not the alpha-receptor cells, were able to migrate chemotactically towards a concentration gradient of ligand. The molecular basis for the differences in signalling were explored by comparing the pattern of increased phosphorylation of potential substrates for the alpha- and beta-receptors in [32P]orthophosphate labelled intact cells and using an in vitro kinase assay. Certain of the observed substrates were common for the two receptors, whereas others were specific for either one. We conclude that certain of the known PDGF induced cellular effects are transduced only by the beta-receptor; the presence of alpha-receptor-specific substrates suggests that there are also alpha-receptor-specific signals, which have yet to be identified. PMID- 1311252 TI - Immunoglobulin V gene replacement is caused by the intramolecular DNA deletion mechanism. AB - Circular DNA resulting from V gene replacement was studied with an A-MuLV transformed cell line containing ablts. This cell line undergoes V gene replacement at elevated temperatures in the immunoglobulin (Ig) heavy chain (H) gene. Examination of circular DNA revealed that a heptamer-related sequence (TACTGTG) within the coding region of VDJ was joined to the recombination signal sequence (RSS) of a germline VH segment. This provides direct evidence for a intramolecular DNA deletion mechanism for V gene replacement. In the pre-B cell line as well as in in vivo lymphocytes, unusual circular DNAs were found which were structurally similar to the V gene replacement circles. They represented excision products of the deletion type recombination between one complete RSS and a heptamer-like sequence in the Ig H region. PMID- 1311253 TI - Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. AB - Acute promyelocytic leukemia (APL) is due to a chromosomal t(15;17) translocation which involves a novel human gene, Myl, (also named PML) and the retinoic acid (RA) receptor alpha (RAR-alpha) gene. We report here the characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients. Myl displays similarities with a new family of proteins of which some members are fused to protooncogenes in the transforming proteins RFP-ret and T18. The speckled nuclear localization of Myl, as well as its sequence homology with the 52 kDa component of the RO/SSA ribonucleoprotein particle, suggest that Myl may be present in a ribonucleoprotein complex. In contrast to both Myl and RAR-alpha whose localization is essentially nuclear in the presence or absence of RA, MylRAR which is largely cytoplasmic in the absence of RA appears to be translocated to the nucleus in the presence of RA. Myl and MylRAR can associate in vitro and this association is mediated by a coiled coil in the Myl sequence. In vivo this association results in a colocalization of Myl and MylRAR which is identical to that of MylRAR alone. Studies of activation of transcription from the promoters of several RA target genes indicate that MylRARs have altered transcription activation properties when compared with RAR-alpha. Most notably, MylRAR represses markedly the activity of some RA target promoters in the absence of RA. Western blot analyses of patient samples show that MylRAR is expressed to a much higher level than wild type RAR-alpha originating from the normal allele. Taken together, these results suggest that MylRAR may interfere in a dominant manner with both Myl and RAR functions. PMID- 1311254 TI - DNA binding by c-Ets-1, but not v-Ets, is repressed by an intramolecular mechanism. AB - The E26 avian retrovirus causes an acute leukemia in chickens and transforms both myeloid and erythroid cells. The virus encodes a 135 kDa fusion protein which contains amino acid sequences derived from the viral Gag protein and the two cellular transcription factors c-Myb and c-Ets-1p68. Previously we have shown that like v-myb, v-ets on its own is also active in transformation, but only within the erythroid lineage. To understand better the mechanisms involved in the oncogenic activation of c-Ets-1p68, we used the polyoma PEA3 element, a known Ets binding site, to compare the sequence-specific DNA binding and transactivating properties of v-Ets and c-Ets-1p68. Using Ets protein synthesized in rabbit reticulocyte lysate in gel retardation assays, we detected little binding of c Ets-1p68 to an oligonucleotide containing the PEA3 motif whereas v-Ets bound strongly. However, in transient cotransfection assays in chicken embryo fibroblasts both c-Ets-1p68 and v-Ets transactivated transcription from a heterologous promoter linked to PEA3 elements. Interestingly, fragments of c-Ets 1p68 with strong DNA binding activity could be produced by limited proteolysis, indicating that the DNA binding domain is repressed within the full-length molecule. By deletion mapping the DNA binding domain was localized to the most highly conserved region of the Ets-related proteins known as the ETS domain. The C-terminus as well as a region in the middle of the polypeptide chain are involved in repression of DNA binding in c-Ets-1p68. Significantly, v-Ets contains a 16 amino acid substitution at the C-terminus. Our results suggest that intramolecular repression of DNA binding is a regulatory mechanism in c-Ets-1p68 which is lost in v-Ets. PMID- 1311255 TI - In vivo topoisomerase II cleavage of the Drosophila histone and satellite III repeats: DNA sequence and structural characteristics. AB - We have identified two classes of in vivo topoisomerase II cleavage sites in the Drosophila histone gene repeat. One class co-localizes with DNase I hypersensitive regions and another novel class maps to a subset of consecutive nucleosome linker sites in the scaffold-associated region (SAR) of the histone gene loop. Prominent topoisomerase II cleavage is also observed in one of the linker regions of the two nucleosomes spanning satellite III, a centromeric SAR like DNA sequence with a repeat length of 359 bp. At the sequence level, in vivo topoisomerase II cleavage is highly site specific. Comparison of 10 nucleosome linker sites defines an in vivo cleavage sequence whose major characteristic is a prominent GC-rich core. These GC-rich cleavage sites are flanked by extensive arrays of oligo(dA).oligo(dT) tracts characteristic of SAR sequences. Treatment of cells with distamycin selectively enhances cleavage at nucleosome linker sites of the SAR and satellite regions, suggesting that AT-rich sequences flanking cleavage sites may be involved in determining topoisomerase II activity in the cell. These observations provide evidence for the association of topoisomerase II with SARS in vivo. PMID- 1311256 TI - Interstitial telomeres are hotspots for illegitimate recombination with DNA molecules injected into the macronucleus of Paramecium primaurelia. AB - DNA molecules injected into the macronucleus of Paramecium primaurelia replicate either as free linear telomerized or chromosome integrated molecules. In the present study we show that when a 1.77 kb BamHI DNA fragment harbouring the his3 gene of Saccharomyces cerevisiae was microinjected into the macronucleus, a fraction of the molecules are integrated into the chromosome via an illegitimate recombination process. The injected molecules were mostly inserted at their extremities at multiple points in the genome by replacing the Paramecium sequences. However, insertion sites were not totally at random. Roughly 30% of the molecules were integrated next to or in telomeric repeats. These telomeric repeats were not at the extremities of chromosomes but occupy an internal or interstitial position. We argue that such sites are hotspots for integration as the probability of random insertion near or in an interstitial telomeric site, of which there are 25-60 in a macronucleus is between 5 x 10(-4) and 3 x 10(-5). PMID- 1311257 TI - IS10 transposase mutations that specifically alter target site recognition. AB - IS10 inserts preferentially into particular hotspots. We describe here mutations of IS10 transposase, called 'ATS' that confer Altered Target Specificity. These mutations yield a general relaxation in target specificity but do not affect other aspects of transposition. Thus, the preference for specific nucleotide sequences at the target site can be cleanly separated from other steps of the transposition reaction. Eleven ATS mutations identified in a genetic screen occur at only two codons in transposase, one in each of two regions of the protein previously implicated in target site interactions (Patch I and Patch II). Genetic analysis suggests that mutations at the two ATS codons affect the same specific function of transposase, thus raising the possibility that Patch I and Patch II interact. For wild-type IS10, insertion specificity is determined in part by a specific 6 bp consensus sequence and in part by the immediately adjacent sequence context of the target DNA. The ATS mutations do not qualitatively alter the hierarchy with which base pairs are recognized in the consensus sequence; instead, sites selected by ATS transposase exhibit a reduction in the degree to which certain base pairs are preferred over others. Models for the basis of this phenotype are discussed. PMID- 1311259 TI - Increased frequency of 2,4,6-trinitrophenyl (TNP)-specific, H-2b-restricted cytotoxic T lymphocyte precursors in transgenic mice expressing a T cell receptor beta chain gene from an H-2b-restricted, TNP-specific cytolytic T cell clone. AB - T cell antigen receptors (TcR) expressing V alpha 10/J alpha BBM142 genes in association with beta chains containing J beta 2.6 elements were found to be predominant among 2,4,6-trinitrophenyl (TNP)-specific, H-2b-restricted cytolytic T cell lines (CTL). To assess the relative contribution of the TcR beta chain to the TNP specificity as well as to the selection of the respective TcR alpha chain elements we generated transgenic mice expressing the TcR beta chain of the H 2b/TNP-specific CTL clone BT7.4.1. The TcR of this clone does not belong to the type predominant among H-2b/TNP-specific CTL, as it consists of an alpha chain encoded by a V alpha 8/J alpha DO gene rearrangement and a V beta 2/J beta 1.1 containing beta chain. In the transgenic mice almost all T cells exclusively express the transgenic V beta 2 gene, as a result of allelic exclusion. TNP specific, H-2b-restricted precursors were found at 7- to 8-fold higher frequency in these mice as compared with non-transgenic littermates. In H-2b/d heterozygous transgenic mice, an increased frequency of TNP-specific precursors was found only in H-2b, but not in H-2d-restricted CTL. Analysis of H-2b/TNP-specific CTL lines derived from V beta 2-transgenic mice indicated a preferential association of the transgenic TcR beta chain with endogenous alpha chains encoded by V alpha 8 and J alpha BBM142 genes. This suggests that the hapten TNP is recognized like typical peptide antigens by combinatorial TcR alpha and beta contact sites. PMID- 1311258 TI - Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen. AB - The purified human single-stranded DNA binding protein, replication protein A (RP A), forms specific complexes with purified SV40 large T antigen and with purified DNA polymerase alpha-primase, as shown by ELISA and a modified immunoblotting technique. RP-A associated efficiently with the isolated primase, as well as with intact polymerase alpha-primase. The 70 kDa subunit of RP-A was sufficient for association with polymerase alpha-primase. Purified SV40 large T antigen bound to intact RP-A and to polymerase-primase, but not to any of the separated subunits of RP-A or to the isolated primase. These results suggest that the specific protein-protein interactions between RP-A, polymerase-primase and T antigen may play a role in the initiating of SV40 DNA replication. PMID- 1311260 TI - Preferential positive selection of V alpha 2+ CD8+ T cells in mouse strains expressing both H-2k and T cell receptor V alpha a haplotypes: determination with a V alpha 2-specific monoclonal antibody. AB - A monoclonal antibody, B20.1, was generated by fusing spleen cells from a Lou rat immunized with a soluble alpha/beta T cell receptor (TcR; V alpha 2/V beta 2) to mouse myeloma cells. Analysis of a panel of V alpha 2 mRNA-expressing T cell lines, hybridomas and transfectants revealed that the B20.1 antibody was specific for murine TcR V alpha 2 chains. The V alpha 2+ T cell population was examined in various inbred strains by two-color immunofluorescence using B20.1 and CD4- and CD8-specific antibodies with the following results: (a) the B20.1 antibody detected most members of the TcR V alpha 2 subfamily in the four TcR V alpha haplotypes tested; (b) in most strains examined, TcR V alpha 2 expression was biased to the CD4 subset (7.4%-17.4% V alpha 2+ T cells) as compared to the CD8 compartment (3.8%-13.3%); (c) TcR V alpha 2 expression was not influenced by Mls gene products and (d) increased positive selection of V alpha 2+ CD8+ T cells by H-2k major histocompatibility complex molecules occurred in all murine strains tested of the TcR V alpha a, but not in those bearing the TcR V alpha b haplotype. PMID- 1311261 TI - The CD27 membrane receptor, a lymphocyte-specific member of the nerve growth factor receptor family, gives rise to a soluble form by protein processing that does not involve receptor endocytosis. AB - CD27 is a transmembrane glycoprotein found exclusively on human T and B lymphocytes. It belongs to a recently identified receptor family, whose members are involved in cell differentiation and survival. This family includes the nerve growth factor receptor, two different types of tumor necrosis factor, receptors the Fas antigen, and the B cell-specific protein CD40. T cell activation via the antigen receptor strongly enhances CD27 membrane expression, suggesting a role for CD27 during T cell differentiation. A soluble form of CD27 (sCD27) is released into the supernatant of activated T cells, and detected in serum and urine of healthy individuals and patients. We have investigated the mechanism underlying the generation of sCD27. One mRNA encodes both the transmembrane receptor and sCD27, as shown by cDNA transfection. In line with this, only one CD27 precursor protein is found, that is processed to the mature receptor by extensive O-linked glycosylation. All newly synthesized protein is rapidly transported to the plasma membrane; no internal pool of mature protein is detectable. The transmembrane form gives rise to sCD27 after arrival at the cell surface, most likely via a proteolytic event, that does not involve receptor internalization. PMID- 1311262 TI - Mouse autoreactive gamma/delta T cells. II. Molecular characterization of the T cell receptor. AB - A panel of dendritic epidermal T cell (DETC) lines, and hybridomas derived from them, has been shown to spontaneously secrete lymphokines in the absence of added stimuli, which suggests that these cells are autoreactive. These cell lines are characterized by the expression of a V gamma 1.1C gamma 4/V delta 6 type T cell receptor (TcR), but several of the DETC lines also express a second TcR. Sequence analyses of these gamma/delta TcR revealed that the gamma chains were identical and that the delta chains, while not identical, were quite restricted in diversity, indicating that these receptors may recognize a common or closely related group of antigens. Analysis of hybridomas derived from newborn thymocytes identified six hybridomas that spontaneously secrete lymphokines. Five hybrids expressed a V gamma 1.1C gamma 4/V delta 6 receptor and one hybrid a V gamma 1.1C gamma 4/V delta 4 receptor that had a close structural relationship to the DETC gamma/delta TcR associated with spontaneous lymphokine secretion. gamma/delta TcR of the C gamma 4 type expressed by splenic hybridomas that did not spontaneously secrete lymphokines revealed no such relationship. Curiously, like the DETC, several of the thymocyte hybridomas that spontaneously secreted lymphokines expressed a second TcR, V gamma 2C gamma 1 or V gamma 3C gamma 1, apparently in association with the same delta chain that paired with the C gamma 4 chain. The presence of spontaneous lymphokine-secreting gamma/delta T cells with such highly homologous TcR in both the thymus and skin suggests a thymic origin for the autoreactive DETC and that these cells recognize a common or closely related group of self-antigens. PMID- 1311263 TI - Variation in human T cell receptor V beta and J beta repertoire: analysis using anchor polymerase chain reaction. AB - Anchor polymerase chain reaction has been applied to the study of human T cell receptor beta chain repertoire in peripheral blood. The use of this technique has demonstrated that considerable variation in V beta and J beta usage exists, both within and between individuals. Particular V beta families, including V beta 6, V beta 4 and V beta 12 are commonly utilized, while families such as V beta 10, V beta 11 and V beta 15 are rare in all individuals studied. Marked interindividual variation in V beta usage was detected for V beta 12 and V beta 4. Biased usage of J beta elements is a prominent feature of peripheral repertoire, while there is no evidence for preferential V beta-J beta recombination events. Biased J beta usage in expressed V beta-D beta-J beta-C beta transcripts, subject to selection, was the same as that in aberrant, unselected D beta-J beta-C beta transcripts, implying that bias resulted from events relating to rearrangement itself, in the absence of selection. N-region diversity showed some evidence for preferential insertion of deoxyguanosine, consistent with the action of terminal deoxytransferase. No P-nucleotide incorporation was seen in association with intact J beta elements. These data provide evidence of some of the variation in human T cell receptor beta chain repertoire and provide a basis for comparisons with sequences which may be obtained in autoimmune and superantigen-mediated diseases. PMID- 1311264 TI - Extrathymic origin of V gamma 1/V delta 6 T cells in the skin. AB - The dendritic epidermal cells (dEC) from young (8-week-old) athymic mice were found to express mRNA for gamma/delta T cell receptors (TcR). The mRNA found in the dEC from athymic mice was expressed only for V gamma 1-J gamma 4-C gamma 4 and V delta 6-J delta 1-C delta with both chains having productive rearrangements and junctional diversity. On the other hand, the dEC from euthymic mice carried V gamma 5-J gamma 1-C gamma 1 and V delta 1-J delta 2-C delta in addition to the V gamma 1/V delta 6 subset found in athymic mice. Therefore, this V gamma 1/V delta 6 subset, which has been implicated in the murine gamma/delta T cell responses to mycobacterial antigens and self heat-shock proteins, is the product of extrathymic maturation in the dEC from both athymic and euthymic mice. PMID- 1311265 TI - Preferential association of alpha and beta chains of the T cell antigen receptor. AB - The cytotoxic T lymphocyte (CTL) clone B6.2.16 expresses a V beta 8.2/J beta 2.3/C beta 2-encoded T cell receptor (TcR) beta chain and an alpha chain that is encoded by a novel V alpha gene segment, J alpha 27 and C alpha. While expression of V alpha B6.2.16 and J alpha 27 is not detectable in lymph node cells of normal C57BL/6 mice, expression of these gene segments was readily seen in transgenic mice expressing the rearranged beta chain gene of the B6.2.16 T cell clone. This finding indicates that only a limited number of alpha chains can associate with the B6.2.16 beta chain and strongly suggests that the size of the TcR repertoire of mature T cells is not only limited by TcR ligand-mediated thymic selection but also by restrictions in alpha-beta combinatorial chain association. PMID- 1311266 TI - Introduction of a foreign gene (Escherichia coli lacZ) into rat neostriatal neurons using herpes simplex virus mutants: a light and electron microscopic study. AB - Introducing genes into adult neurons in vivo may be a useful experimental tool for studying and modifying neuronal function. In this study two herpes simplex virus type 1 (HSV-1) mutants were used to examine the capability of different types of neostriatal neurons to express a foreign gene introduced through viral infection. In these HSV-1 mutants (7134 and RH105) the Escherichia coli gene, lacZ, under the control of viral promoters active during the early phase of infection, was substituted for viral genes (ICPO and TK, respectively) needed for efficient replication in the nervous system. Adult male rats received unilateral injections of HSV-1 mutant 7134 or RH105 into the neostriatum. Animals survived for 1 to 70 days with no apparent adverse physiological or behavioral effects. At the injection site, both mutant viruses produced focal tissue necrosis and reactive gliosis. Histochemical detection of the lacZ gene product, beta galactosidase (beta Gal), revealed extensive labeling of neurons with mutant 7134 and relatively limited neuronal labeling with the mutant RH105. Mutant 7134, which is capable of some replication in cells, conferred beta Gal expression in cells over an area that was twofold greater than the necrotic area. In contrast, mutant RH105, which cannot replicate in cells, produced a zone of beta Gal labeled cells only two-thirds the area of the necrotic core. Both medium- and large-sized neostriatal neurons were positive for beta Gal, and a higher proportion of large cells were labeled as compared to other neuronal populations in the normal striatum. A few glial cells were also beta Gal-positive. Retrograde transport of virus to the substantia nigra pars compacta and to the cortex was minimal and occurred only with mutant 7134. No evidence was seen for anterograde transport. Immunohistochemical localization of beta Gal at the ultrastructural level after inoculation with mutant 7134 revealed that both types of medium-sized neurons (spiny and aspiny types), as well as large neurons, were infected 3 days following inoculation. Immunoreactive neurons ranged from severely pathologic to remarkably healthy. Some of the axon terminals that contacted beta Gal immunoreactive dendrites and spines were degenerated. These results demonstrate that in the adult rat replication-deficient HSV-1 vectors injected intrastriatally can be used to express a foreign gene in at least three types of neostriatal neurons, while maintaining the long-term survival and general health of the injected animals. The neurotoxicity induced by HSV-1 mutants may still be considerable, however, and ways of minimizing neuropathological effects need to be addressed. PMID- 1311267 TI - Inhibition of cerebrospinal fluid formation by omeprazole. AB - Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+) K(+)-ATPase inhibitors such as ouabain. PMID- 1311268 TI - Persistence of plasmid DNA and expression in rat brain cells in vivo. AB - The purpose of this study was to determine whether plasmid DNA is able to persist in nondividing or slowly dividing brain cells in vivo. A new cationic lipid formulation which contains 70 mol% of DOTMA (N[1-(2,3-dioleyloxy)propyl]-N, N, N trimethylammonium) and 30 mol% of cholesterol was used to transfect reporter genes into fetal brain cells in culture that were then transplanted into adult host brains. Gene expression was localized both to glial and neuronal cells after transfection of fetal brain cells with pRSVLac-Z, the gene coding for Escherichia coli beta-galactosidase protein. After the transfection of pRSVL plasmid which contains the firefly luciferase gene into fetal brain cells that were transplanted, substantial amounts of luciferase and pRSVL DNA were present in the host brains for 1 to 2 months. These results have implications for intracerebral viral infections and gene therapy of brain disorders. PMID- 1311269 TI - Maintenance of long-term adaptation of synaptic transmission requires axonal transport following induction in an identified crayfish motoneuron. AB - Motoneurons can adapt to altered levels of electrical activity by effecting semi permanent changes in their neuromuscular synaptic physiology. In the present study, we tested the hypothesis that maintenance of activity-dependent long-term adaptation of synaptic transmission in a crayfish abdominal extensor motoneuron (phasic axon 3) required axonal transport following induction. Intact crayfish were chronically wired for periodic in vivo stimulation of axon 3. Periodic unilateral stimulation for 3-5 consecutive days (2 h/day) induced long-term adaptation (LTA) of neuromuscular synaptic transmission in axon 3. Initial EPSP amplitudes (measured at 0.1 Hz) were significantly reduced to approximately 40% of contralateral control amplitudes over a 7-day poststimulation period. Additionally, synaptic depression during 5 Hz test stimulation of axon 3 was significantly less in chronically stimulated neurons: excitatory postsynaptic potential (EPSP) amplitudes measured after 20 min of 5 Hz test stimulation (final EPSPs) were significantly larger in conditioned neurons than in unstimulated controls. The depression of initial EPSP amplitudes persisted for 7 days postinduction, while the increased synaptic stamina persisted for 4 days but was absent at 7 days postinduction. Axotomy of axon 3 following induction of LTA had no effect on long-term maintenance of the activity-induced reduction in initial EPSP amplitudes. Initial EPSP amplitudes in conditioned, axotomized neurons were still reduced to 42% of control amplitudes over the 7-day postinduction period. In contrast, postinduction axotomy of axon 3 elicited an accelerated decay of the enhanced synaptic stamina. Following axotomy, final EPSP amplitudes were significantly larger in conditioned neurons for only 1 day poststimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311270 TI - Stable expression of high affinity NK1 (substance P) and NK2 (neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells. AB - Stable CHO cell clones which selectively express all three rat tachykinin receptors were established by transfection. The binding of radiolabled substance P and neurokinin A (substance K) to CHO clones expressing the NK1 and NK2 receptors, respectively, were saturatable and of high affinity (Kd = 0.17 nM (NK1); 3.4 nM (NK2)). Scatchard analysis of the binding data indicated for both receptors binding to a single population of binding sites, and competition binding studies showed that the binding specificities of the receptors corresponded to those of classical NK1 and NK2 receptors. In contrast, the binding of eledoisin to the NK3 receptor expressed in the transfected CHO cells was of low affinity (IC50 = 240 nM) compared to the high affinity of the receptor found when it was transiently expressed in COS-7 cells (IC50 = 8 nM). However, in both cases the receptor exhibited the specificity of a classical NK3 receptor. The established cell clones may provide an important tool for further analysis of the molecular mechanisms involved in binding, activation, and coupling of receptors for tachykinin peptides. PMID- 1311271 TI - Distinct biochemical mechanisms for cAMP-dependent transcription of CYP17 and CYP21. AB - Optimal steroidogenic capacity in the adrenal cortex is regulated by ACTH via cAMP and involves transcription of the genes encoding the adrenocortical steroid hydroxylases. The microsomal steroid hydroxylases, P45017 alpha and P450C21, are encoded by CYP17 and CYP21, respectively. These genes are thought to have arisen from a common progenitor gene and are coordinately regulated by ACTH. The cAMP responsive sequences (CRS) located in the 5'-flanking regions of these genes are distinct from one another and from known consensus sequences imparting cAMP responsiveness in other genes. The CYP21 CRS binds a putative adrenal-specific nuclear protein. In contrast, the CYP17 CRSI binds a ubiquitous protein that is apparently active only in steroidogenic cells. Thus the ACTH-dependent transcription of these two genes, which have a common evolutionary origin and are coordinately expressed in the adrenal cortex, involves distinct biochemical mechanisms. PMID- 1311272 TI - Transcriptional derepression of the murine Cyp1a-1 gene by mevinolin. AB - In mouse hepatoma Hepa-1c1c7 cultures, polycyclic aromatic compounds such as benzol[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) activate the Cyp1a-1 (cytochrome P(1)450) and Nmo-1[NAD(P)H:menadione-oxidoreductase] genes, two members of the aromatic hydrocarbon (Ah)-responsive gene battery. Mevinolin is known to inhibit 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase (EC 1.1.1.34), the rate-limiting step in cholesterol biosynthesis. We show here that in the absence of TCDD, mevinolin markedly increases Cyp1a-1 transcription, CYP1A1 mRNA and protein levels and enzyme activity, and NMO1 mRNA concentrations. Addition of mevalonate, the product of HMG-CoA reductase activity, fails to reverse the effects of mevinolin. In fact, when used at high concentrations, mevalonate activates Cyp1a-1 transcription. Mevinolin-induced Cyp1a-1 gene activation: (1) occurs independently of the lipid content of the growth medium, (2) is not suppressed by adding 25-hydroxycholesterol, which blocks MHG-CoA reductase activity, and (3) requires a functional Ah receptor and unimpaired nuclear translocation of the receptor. It is possible that an unknown metabolite (or metabolites) of mevinolin activates Cyp1a-1 expression and that high concentrations of mevalonate act via the same mechanism. Using chimaeric plasmids that contain different lengths of Cyp1a-1 5' flanking regions fused to the bacterial neomycin (neo) gene, we find that the mevinolin effect on Cyp1a-1 induction requires the 5' flanking sequences between -1647 and -824, which are also needed for TCDD induction. Mevinolin, however, is not a ligand for the Ah receptor. Gel mobility shift assays revealed that Cyp1a-1 activation caused by mevinolin does not involve the ligand-dependent formation of a functional Ah receptor-dependent DNA-binding complex, but instead appears to be correlated with release of a putative repressor from its cognate DNA site. Our results suggest that the basel level of Cyp1a-1 transcription is maintained by an unknown negative regulatory factor. We propose that Cyp1a-1 transcriptional activation can result not only from induction by polycyclic aromatic compounds but also from derepression by mevinolin, independent of HMG-CoA reductase inhibition. PMID- 1311273 TI - Intracellular pH in isolated Necturus duodenal mucosa exposed to luminal acid. AB - Regulation of intracellular pH (pHi) and its maintenance within physiological ranges during exposure to luminal acid was studied in isolated Necturus duodenal mucosa using liquid sensor microelectrodes. Exposure of the mucosa to luminal pH 2.7 caused significant intraepithelial acidification. Subsequent removal of HCO3 /CO2 (HEPES/O2 substitution) from the serosal perfusate caused a further decrease of pHi. Blocking of HCO3- transport across the basolateral cell membrane by addition of 4-acetamido-4,isothiosyanostilbene-2,2-disulfonic acid (SITS) to serosal perfusate also caused a slight but significant decrease of pHi. Removal of Na+ (choline substitution) from the serosal perfusate during acid exposure likewise caused a significant decrease in pHi, as did serosal addition of an inhibitor of Na+/H+ antiport, 1 mmol/L amiloride. When Na+ was removed from the serosal perfusate after HCO3- removal, pHi first rapidly acidified; this was followed after an initial 5-minute steady state by an uncontrolled progressive acidification at a rate of 0.33 pH unit/15 min without any further steady state. A similar but weaker effect could also be shown with amiloride addition. The epithelial surface pH was 7.13 +/- 0.08 at the apex of mucosal villus and 7.42 +/ 0.11 (n = 5) in the cryptal area between the villi, i.e., greater than 1 pH unit higher than that of the luminal bulk solution (pH 6), thus suggesting active alkalization of the epithelial surface. Removal of serosal HCO3-/CO2 decreased surface pH significantly both at the villus apex and at the cryptal area, suggesting that the surface alkalization is mediated by transport of serosal HCO3 to the epithelial surface. The data suggest that pHi in acid-exposed duodenal mucosa is primarily maintained within physiological range by an HCO3(-)-dependent mechanism, which, at least in part, exerts its action extracellularly by forming an alkaline buffer layer at the epithelial surface. If adequate serosal (or systemic) HCO3- is not available, a second-line Na(+)-dependent and amiloride sensitive pHi-regulatory mechanism, presumably an Na+/H+ antiport, becomes the main regulator of pHi. PMID- 1311274 TI - Vitamin D and mineral deficiencies increase the plasma membrane calcium pump of chicken intestine. AB - The basolateral membrane of the enterocyte was previously shown to contain an adenosine triphosphate-dependent calcium pump. Using immunological procedures, the localization of the Ca2+ pump in chick intestine, and the effect of dietary variables on the concentration of the pump, were studied. A monoclonal antibody produced against the human erythrocyte calcium pump was shown to cross-react with a chick intestinal Ca2+ pump epitope. The most intense staining of intestinal tissue, as determined immunohistochemically, occurred at the basolateral membrane of the duodenum, jejunum, ileum, and colon, with minor staining elsewhere. By the Western blotting procedure, vitamin D repletion of vitamin D-deficient chicks was shown to significantly increase the concentration of the Ca2+ pump epitope of duodenal, jejunal, and ileal mucosa by a factor of 2-3. Chicks were also fed diets deficient in calcium or phosphorus, a situation known to result in the stimulation of the synthesis of calbindin-D28k and an enhancement of the efficiency of Ca2+ absorption. Adaptation of the chicks to these deficient diets was verified by an increase in intestinal levels of calbindin-D28k, and is now shown to increase the Ca2+ pump epitope. From these immunological studies, it seems apparent that dietary variables that enhance intestinal Ca2+ absorption also increase the amount of the intestinal basolateral Ca2+ pump. PMID- 1311275 TI - Role of hepatitis C virus in acute non-A, non-B hepatitis in Greece: a 5-year prospective study. AB - The prevalence of hepatitis C virus (HCV) infection in 182 prospectively followed adult patients (110 males, 72 females) with acute non-A, non-B hepatitis and its correlation with progression to chronic hepatitis were studied. These patients were followed for a mean of 24.7 +/- 13.1 (range, 6-57) months. By using a specific enzyme immunoassay for the detection of antibodies against C100-3 polypeptide of HCV, 96 (52.7%) were found antibody positive. HCV was implicated in 64/89 (71.9%) of the cases with classical parenteral exposure but only in 18/64 (28.1%) of the community-acquired cases. Progression to chronic hepatitis was observed more frequently in antibody-positive than in antibody-negative cases (60/96 or 62.5% vs. 27/86 or 31.4%, P = 0.00002). Progression was also observed more often in males than in females (66/112 or 58.9% vs. 21/70 or 30.0% P = 0.0001), both in the antibody positive (48/68 or 70.6% vs. 12/28 or 42.9%, P = 0.01) and in the antibody negative (18/44 or 40.9% vs. 9/42 or 21.4%, P = 0.043) cases. These data indicate that (a) acute hepatitis due to HCV is characterized by a high rate of chronicity, especially in males, and (b) a non-A, non-B, non-C agent or a different strain of HCV may be responsible for the majority of the community-acquired cases of non-A, non-B hepatitis in Greece. PMID- 1311276 TI - Molecular phylogenetic typing of pandemic isolates of Salmonella enteritidis. AB - Salmonella enteritidis is now the most common Salmonella serovar in many countries. We have used cloned DNA probes to analyze genome interrelationships between strains chosen to represent the current S. enteritidis pandemic, and included designated type strains of the seven subspecies of Salmonella in order to compare the levels of discrimination of probes. DNA sequence divergence and rearrangements were analyzed in and around the rfa, fim and umuDC loci, and around insertion sites of the Salmonella-specific DNA insertion element, IS200. The S. enteritidis isolates showed a high degree of genome homogeneity. Chromosomal genetic loci exhibited characteristic DNA sequence divergence between subspecies of Salmonella, but no intraserovar divergence or difference with the subspecies I type strain was observed for S. enteritidis. The locus umuDC was not found in S. enteritidis. S. enteritidis contains a conserved and a variable site of insertion of insertion sequence IS200 and the analysis of DNA rearrangements around the second of these sites showed that three distinct evolutionary lines or races exist within pandemic isolates associated with human gasteroenteritis. IS200 profiles of a range of U.K. isolates of the epidemic phage type PT4 showed that all belonged to a single clonal line. PMID- 1311277 TI - NAD-dependent glutamate dehydrogenase from Pseudomonas aeruginosa is a membrane bound enzyme. AB - Measurements of the deaminating activity of NAD-dependent glutamate dehydrogenase (NAD-GDH) in Pseudomonas aeruginosa strain 8602 (PAC 1) showed an initially constant rate that gave way to a 3.5-fold increased rate on prolonged incubation. Only the faster rate was observed when assay mixtures were preflushed with nitrogen or were treated with the detergent Triton X-100. Comparison of the intracellular distribution of NAD-GDH with marker enzymes showed it to be associated with the cytoplasmic membrane. The results suggest that NAD-GDH may be linked to oxygen through an electron-transport system. PMID- 1311278 TI - Construction of yeast artificial chromosome (YAC) clone banks covering three genome equivalents and isolation of YACs containing the human gene encoding tumor necrosis factor receptor beta. AB - Yeast artificial chromosome (YAC) banks covering in total about three haploid genome equivalents were constructed using a human Epstein-Barr-virus-transformed B lymphocytic cell line. Two clone banks were made: 20,000 clones with average inserts of 350 kb in the pYAC4 vector and 9850 clones with average inserts of 180 kb using vectors pJS89 and pJS91. Direct comparison of pYAC4 with pJS89 and pJS91 showed pYAC4 to be the most suitable cloning vector. Two partial banks with average insert sizes of 220 kb for human endothelial cell DNA and epithelial HEp2 cell DNA were also constructed, each covering 10% of the haploid genome. A rapid, three-step PCR screening procedure for isolation of individual YAC clones was developed and used to identify two clones encoding TNF-R beta. These clones cover about 200 kb and have 170 kb in common. TNF-R beta is 9.3 kb long and contains two introns within the protein-coding sequence. PMID- 1311279 TI - Structure of the murine lactotransferrin gene is similar to the structure of other transferrin-encoding genes and shares a putative regulatory region with the murine myeloperoxidase gene. AB - The structure and nucleotide sequence of the murine lactotransferrin-encoding gene (LTF) deduced partly by direct sequencing of genomic clones in the lambda phage vector and partly by enzymatic amplification of genomic DNA segments primed with the oligodeoxyribonucleotide primers homologous to the cDNA sequence. The lambda phage clones contained the 5' half of the gene corresponding to the first eight exons and an incomplete ninth exon interrupted by eight introns. Genomic clones corresponding to the 3' half of the LTF gene could not be obtained on repeated attempts from two different mouse genomic libraries, suggesting the possible presence of unclonable sequences in this part of the gene. Hence, PCR was used to clone the rest of the gene. Four out of the presumed eight remaining introns were cloned along with the flanking exons using PCR. Comparison of the structure of the LTF gene with those of the two other known transferrin-encoding genes, human serum transferrin-encoding gene and chicken ovotransferrin-encoding gene reveals that all three genes have a very similar intron-exon distribution pattern. The hypothesis that the present-day transferrin-encoding genes have originated from duplication of a common ancestral gene is confirmed here at the gene level. An interesting finding is the identification of a region of shared nucleotides between the 5' flanking regions of the murine LTF and myeloperoxidase encoding genes, the two genes expressed specifically in neutrophilic granulocytes. PMID- 1311280 TI - Production of hydroxyl radicals and their disassociation from myocardial cell injury during calcium paradox. AB - The production of hydroxyl radicals during calcium paradox injury was investigated by measuring the production of 2,5-dihydroxybenzoic acid (2,5-DHBA) from salicylate. Four groups of rats were analyzed. In the first group, isolated hearts were perfused with calcium-free medium for 10 minutes followed by perfusion with medium containing Ca++ for 10 minutes. In the other groups, 0.25 microM N,N'-diphenyl-1,3-phenylenediamine (DPPD), 80 microM cytochrome c, or 450 U/ml catalase was added. Coronary effluent was analyzed for the presence of 2,5 DHBA, and tissue sections were examined using light microscopy. In the first group, 2,5-DHBA production began during the calcium-free period, peaked tenfold 60-90 sec. into the Ca repletion period, and declined thereafter. The increase in 2,5-DHBA was accompanied by severe cell damage. Cytochrome c reduced 2,5-DHBA production, and catalase almost completely inhibited 2,5-DHBA production, while DPPD had no effect on 2,5-DHBA production. None of the three additives provided any complete morphological protection. The data provide evidence for the production of hydroxyl radicals during calcium-paradox injury, that their production is dependent upon the presence of hydrogen peroxide, and that cell damage in the calcium paradox is not primarily mediated by the extracellular hydroxyl radicals. PMID- 1311281 TI - Urate causes the human polymorphonuclear leukocyte to secrete superoxide. AB - The human polymorphonuclear leukocyte generates O2-. and H2O2 when it is treated with uric acid. A transition metal catalyzed reaction between O2-. and H2O2 can give the hydroxyl radical and myeloperoxidase forms hypochlorous acid from H2O2 and chloride. Therefore, the uric acid-induced secretion of oxidants may be responsible for a large part of the inflammation associated with gout. PMID- 1311282 TI - Cholera toxin inhibits interleukin-2-induced, but enhances pertussis toxin induced T-cell proliferation: regulation by cyclic nucleotides. AB - To understand the signals transmitted by interleukin-2 (IL-2) during T-cell proliferation, the effect of this cytokine was compared to the bacterial product pertussis toxin (PT). Both IL-2 and PT induced the incorporation of [3H]thymidine into T cells. Cholera toxin (CT) inhibited IL-2-induced, but enhanced PT-induced T-cell proliferation. The effect of CT is mimicked by the cyclic AMP (cAMP) analogue 2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dicAMP) or by the phosphodiesterase inhibitors isobutylmethylxanthine and aminophylline. Measurement of the intracellular level of cAMP showed that CT enhanced this level during both IL-2 or PT incubation with T cells. To delineate the differential effects of cAMP on IL-2 versus PT activity, it was observed that the blocker of intracellular calcium (TMB8), or the guanosine triphosphate (GTP) analogue (GTP gamma S) inhibited both PT and IL-2 activities, whereas the protein kinase C (PKC) inhibitor (H7) was without effect for both stimuli. Further experiments showed that both IL-2 and PT stimulate the endogenous level of cGMP and that CT enhanced this level following PT activation, but reduced it following IL-2 activation of T cells. Hence, there is a major difference between IL-2 and PT activation of T cells in as far as their susceptibility to treatment with cholera toxin is concerned. Furthermore, an increase of cGMP level resulted in the enhancement of proliferation, whereas a decrease in cGMP level resulted in the inhibition of proliferation. PMID- 1311284 TI - Human papillomavirus infection in esophageal squamous-cell carcinoma in western countries. AB - Recent studies have suggested that esophageal HPV infection could be a risk factor for esophageal squamous-cell carcinoma. The aims of our study were to assess the presence of HPV esophageal infection among French patients with esophageal squamous-cell carcinoma and to compare the prevalence of this infection among control patients exposed to similar known risk factors (alcohol and tobacco) and among non-exposed control patients. All patients had the following investigations: serum immunoglobulin level, T-lymphocyte subsets, cutaneous anergy test and endoscopy with biopsies from tumoral and normal areas. Three different methods were used for HPV-infection diagnosis: histological score, in situ hybridization intended for detection of HPV types 6, 11, 16, 18, 31 and 33, and dot blot intended for detection of HPV types 6/11 and 16/18. Five out of 12 patients with esophageal carcinoma had HPV esophageal infection. This infection did not result from impaired immune status. The most frequently observed types are HPV 16/18. None out of 17 exposed controls and only 1 out of 7 nonexposed controls had HPV esophageal infection (p less than 0.01). HPV infection may be implicated in the development of esophageal squamous-cell carcinoma in association with known risk factors. PMID- 1311283 TI - Antibody responses to a cytochrome c peptide do not correlate with lymphokine production patterns from helper T-cell subsets. AB - This paper examines helper T-cell responses and antibody titres and isotypes following immunization with a peptide antigen in association with three different adjuvants. B10.A mice were primed with pigeon cytochrome c fragment 81-104 in association with the adjuvants complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and alum. Strong antibody responses, dominated by IgG1, were observed upon priming with CFA and IFA. In contrast, priming with alum induced a weak antibody response with little or no detectable antigen-specific IgG1. These differences did not correlate with differences in T-cell priming, as immunization with peptide in association with all three adjuvants induced comparable T-cell proliferative responses and frequencies of antigen-specific cells. In addition, no significant differences in interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and IL-4 production could be found, suggesting that the adjuvants did not differentially affect Th1 and Th2 cells. PMID- 1311285 TI - Patients with cervical cancer produce an antibody response to an HSV-inducible tumour-specific cell polypeptide. AB - Anti-sera raised against HSV-2-infected cells (WI) and the sera of animals bearing tumours (TBS) to HSV-2 transformed cells contain antibodies to a set of tumour-specific cell-coded polypeptides. The specificity of these polypeptides for tumour cells is monitored by the ability of [35S]-L-methionine labelled proteins to be immunoprecipitated by these anti-sera, in contrast to control cells from which the polypeptides are not precipitated. The polypeptides which share an epitope and are co-precipitated are of MWs 90,000 (a doublet), 40,000 and 32,000. The upper 90,000-MW polypeptide (U90) is induced by HSV-2 infection. This communication deals with the 40,000-MW polypeptide which was shown to be immunoprecipitated by TBS and a monoclonal antibody (MAb) raised to the DNA binding proteins of HSV-2-infected cells. Immunological and biochemical studies reveal that the 40,000-MW protein which is immunoprecipitated comprises more than one polypeptide, and that the proteins may need to interact to produce the peptide pattern specific for the tumour form of the immunoprecipitated 40,000-MW protein. WI antisera and TBS both recognise antigens specific for tumour cells in sections of cervical-carcinoma tissue. Sera from patients with cancer of the cervix contain antibodies to a cell-coded polypeptide of MW 40,000, which by peptide analysis is indistinguishable from the 40,000-MW polypeptide induced by HSV-2 infection and immunoprecipitated by WI and TBS. PMID- 1311286 TI - Cell phenotype (CD23)-dependent variation in EBV genome copy numbers within lymphoblastoid cell lines (LCL). AB - Three Epstein-Barr-virus-transformed lymphoblastoid cell lines (LCL) were analysed on the basis of their CD23 expression. Levels of EBV-DNA were compared in the positive and negative subpopulations. Two lines were further analysed with regard to EBNA, cytoplasmic immunoglobulin (cIg) and lytic (EA/VCA) protein expression. Both subpopulations had a similar MHC class-II transcription, but the CD23- subpopulation had a lower plating efficiency and a lower rate of DNA synthesis. In the B6, NAD50 and 0467.3 cell lines, CD23- cells contained 2 +/- 0.2 - 6.4 +/- 3.0 times less EBV DNA than the corresponding CD23+ population. EBNA was expressed in 81 +/- 4.2% - 93 +/- 3.8% of the CD23+ cells and in 0 - 46 +/- 8.0% of the CD23- cells. No CD23+ cells in B6 or NAD50 contained any EA/VCA, while 19 +/- 2.8% - 24 +/- 4.2% of the CD23- cells were positive for the lytic cycle-associated antigens. Of the CD23- cells, 70 +/- 8.6% - 86 +/- 6.0% were positive for cytoplasmic immunoglobulin compared to 14.7 +/- 2.7% - 14.9 +/- 1.8% in the corresponding CD23+ population. We have previously shown that only 18% of the cIg-positive cells were EBNA-positive in the B6 line compared to 94% in the cIg- population. This was open to 2 alternative interpretations: loss of EBV genomes from a fraction of the cells with subsequent differentiation to secretory immunoglobulin production, or down-regulation of EBNA expression in differentiating, EBV-genome-positive cells. Our present findings speak for the first alternative, indicating that a certain proportion of the cells may lose their EBV genomes in both long-established and freshly transformed LCLs. This is accompanied by a reduced percentage of EBNA-positive cells, the disappearance of at least one activation marker (CD23) associated with the virally induced blast transformation, and an increased synthesis of cIg. PMID- 1311287 TI - Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF-7 breast-cancer cells. AB - The MCF-7 cell line is a hormone-responsive human breast-cancer cell line, which has been extensively used in studies of estrogen regulation of cell growth. These studies have indicated that the growth stimulation of the MCF-7 cells by estrogens may be effected by an autocrine mechanism involving several growth factors, such as EGF, TGF alpha and IGF-I and their receptors. We have amplified and cloned tyrosine-kinase-related sequences from the MCF-7 cell mRNA using the polymerase chain reaction and characterized the partial cDNAs obtained by nucleic acid sequencing. Nine tyrosine kinase cDNAs and one serine/threonine kinase cDNA were identified among the amplified sequences. Four different tyrosine kinase genes encoding receptors for fibroblast growth factors (FGFs) were found to be expressed by the MCF-7 cells. In addition, differences were observed in the expression of these members of FGF receptor family in different breast-cancer cells. A putative tyrosine-kinase receptor and a novel serine/threonine kinase were preferentially expressed in estrogen-responsive tumor cell lines. However, no estrogen-dependent regulation of any of the novel tyrosine-kinase receptor mRNAs was found in any of the cell lines including the MCF-7 or ZR-75-I cells, where the expression of the neu proto-oncogene mRNA was decreased during estrogen treatment. The expression of several FGF receptors by breast-cancer cells suggests that FGFs may be involved in their growth regulation and tumorigenesis. PMID- 1311288 TI - Short-term assays for detection of conditional cancerogens. I. Construction of DR CAT Raji cells and some of their characteristics as tester cells. AB - A number of agents including the tumor promoter 12-0-tetradecanoyl-phorbol-13 acetate (TPA) (TPA) can induce an abortive virus cycle in the EBV-non-producer Burkitt's-lymphoma line Raji. Two distant regions, DL and DR, of the EBV genome with almost complete homology carry strong promoters which are induced in an abortive or lytic cycle and additionally function as lytic origins of viral DNA replication. To set up a system in which the activity of EBV-inducing agents can be measured in a quantitative and reproducible fashion, we generated a cell line which carries multiple copies of a DR-promoter chloramphenicol-acetyltransferase (CAT) construct on an episomal vector. CAT activity is low in untreated cells, but high upon treatment of the cells with various EBV-inducing agents. Combinations of different agents can produce an over-additive effect. The Raji-DR CAT cell line may provide a simple quantitative and reproducible test system for EBV-inducing agents, especially for tumor promoters which activate protein kinases C. PMID- 1311289 TI - Prognosis of Hodgkin's disease is not influenced by Epstein-Barr virus latent membrane protein. PMID- 1311290 TI - Effect of chronic respiratory load on cytochrome oxidase activity in diaphragmatic fibers. AB - To determine whether the increase in oxidative capacity after respiratory muscle training with chronic inspiratory loads in sheep is specific to a particular fiber type, we measured cytochrome c oxidase (COX) activity in type I and type II fibers. COX activity in individual fibers was examined histochemically and measured as relative optical density by use of an image processing system. Fiber types were differentiated by the myosin adenosine-triphosphatase reaction. We found that COX activity was higher in both fiber types in the trained diaphragms than in the control diaphragms (P less than 0.01). The increase with training was greater in type II (39%) than in type I fibers (21%), resulting in relatively homogeneous COX activity in all diaphragmatic fibers. The proportion of type I fibers increased from 43.4 +/- 5.4% in the control diaphragm to 53.1 +/- 2.9% in the trained diaphragm, whereas the proportion of type II fibers decreased (P less than 0.001). We conclude that respiratory muscle training activates oxidative enzyme activity in both diaphragmatic fiber types; this activation is differentially more in type II fibers, which also decrease in proportion, and less in type I fibers, which increase in proportion. PMID- 1311291 TI - Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs. AB - The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2-3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model. PMID- 1311292 TI - Reversal of increased microvascular permeability associated with ischemia reperfusion: role of cAMP. AB - Ischemia-reperfusion (IR) is a form of oxidant injury known to increase microvascular permeability in the lung. Agents that increase adenosine 3',5' cyclic monophosphate (cAMP) levels have been shown to have beneficial effects in several models of oxidant lung injury associated with increased microvascular permeability. We investigated the role of adenylate cyclase activation with isoproterenol (ISO) or forskolin (FSK) in reversing the increased microvascular permeability associated with IR. ISO or FSK administered after 45 min of ischemia and 46 min of reperfusion caused a reduction in the capillary filtration coefficient (Kfc) from 1.25 +/- 0.13 to 0.53 +/- 0.08 and 0.55 +/- 0.10 ml.min 1.cmH2O-1.100 g tissue-1, respectively, at 90 min of reperfusion. This reduction in Kfc was accompanied by a rise in perfusate cAMP levels from 16.5 +/- 4.9 and 31.2 +/- 11.9 pmol/ml at 45 min of reperfusion to 444.2 +/- 147.8 and 276.1 +/- 91.0 pmol/ml at 105 min of reperfusion in lungs treated with ISO or FSK, respectively, at 46 min of reperfusion. Dibutyryl cAMP (DBcAMP), a membrane permeable cAMP analogue, mimicked the permeability effect by reducing Kfc to 0.67 +/- 0.15 at 90 min of reperfusion. Significant hemodynamic changes occurred but were small and cannot explain the observed effect on Kfc. Photomicrographs from lungs treated with ISO or FSK revealed a reversal of the morphological manifestations of increased microvascular permeability. We conclude that the increased microvascular permeability associated with IR can be reversed by ISO, FSK, and DBcAMP and that cAMP produced by the lung contributes to the observed reversal. PMID- 1311293 TI - Ventilation-perfusion relationships in the lung during head-out water immersion. AB - Water immersion can cause airways closure during tidal breathing, and his may result in areas of low ventilation-perfusion (VA/Q) ratios (VA/Q less than or equal to 0.1) and/or shunt and, ultimately, hypoxemia. We studied this in 12 normal males: 6 young (Y; aged 20-29 yr) with closing volume (CV) less than expiratory reserve volume (ERV), and six older (O; aged 40-54 yr) with CV greater than ERV during seated head-out immersion. Arterial and expired inert gas concentrations and dye-dilution cardiac output (Q) were measured before and at 2, 5, 10, 15, and 20 min in 35 degrees C water. During immersion, Y showed increases in expired minute ventilation (VE; 8.3-10.3 l/min), Q (6.1-8.2 l/min), and arterial PO2 (PaO2; 91-98 Torr; P less than or equal to 0.05). However, O2 uptake (VO2), shunt, amount of low-VA/Q areas (% of Q), and the log standard deviation of the perfusion distribution (log SDQ) were unchanged. During immersion, O showed increases in shunt (0.6-1.8% of Q), VE (8.5-11.4 l/min), and VO2 (0.31 0.40 l/min) but showed no change in low-VA/Q areas, log SDQ, Q, or PaO2. Throughout, O showed more VA/Q inequality (greater log SDQ) than Y (O, 0.69 vs. Y, 0.47).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311294 TI - Evidence for secretion of high molecular weight mucins by canine tracheal epithelial cells in primary culture: effects of select secretagogues in mucin secretion. AB - The purpose of this investigation was to provide evidence for the secretion of high molecular weight mucins, CTM-A and CTM-B, in primary culture of canine tracheal epithelial (CTE) cells. The cells were isolated from tracheas of mongrel dogs by pronase treatment. Primary cultures of the epithelial cells were established using ICN collagen inserts in Dulbecco's modified Eagle's/F12 medium supplemented with growth factors and could be maintained for up to 23 days. The evidence for the mucin secretion in culture medium and their localization in the cells was established by a) positive immunocytochemical staining using specific antibodies developed against purified native as well as deglycosylated CTM-A and CTM-B; b) incorporation of labeled amino acids, followed by electrophoresis and autoradiography detection of glycoconjugates purified from the culture medium; c) comparison of the amino acid compositions of mucin purified from canine tracheal pouch secretions and that purified from the culture medium; and d) Western blot analyses using specific polyclonal antibodies directed against deglycosylated CTM A and CTM-B. Immunoaffinity purified secreted labeled glycoconjugates were resistant to hyaluronidase treatment. The effects of cyclic AMP (1 x 10(-5) M), dibutyryl cyclic AMP (1 x 10(-5) M), 8-bromocyclic AMP (1 x 10(-5) M), and prostaglandin E1 (1 x 10(-6) M) on mucin secretion by CTE cells were also investigated. Secretion of mucins by CTE cells in culture was considerably more enhanced by 8-bromocyclic AMP than that observed for other secretagogues used in this study. PMID- 1311295 TI - Molecular analysis of the signaling pathway between EnvZ and OmpR in Escherichia coli. AB - OmpR is a DNA-binding protein that regulates transcription of ompF and ompC. The activity of OmpR is controlled by the inner membrane osmosensor, EnvZ. In order to study the signaling process between EnvZ and OmpR, we analyzed two different envZ strains: the envZ473 strain, in which OmpC is constitutively produced and OmpF is fully repressed, and the envZ3 strain, in which the production of OmpC is greatly reduced and OmpF is not fully repressed by high-osmolarity growth conditions. Using direct sequencing of DNA derived from the polymerase chain reaction amplification method, we identified the mutation in the envZ473 strain as a Val-241-to-Gly substitution and the mutation in the envZ3 as an Ala-219-to Val substitution. The relative DNA-binding affinity of OmpR derived from the envZ473 strain was dramatically increased for the upstream sequence of both ompF and ompC. In contrast, OmpR derived from the envZ3 strain was not converted to the high-affinity form. The intracellular levels of OmpR-phosphate, as analyzed by the in vivo phosphorylation approach, significantly increased in the envZ473 strain, while in the envZ3 strain the levels were considerably reduced, relative to those found in the parent strain. The intracellular level of OmpR protein in the envZ473 strain was also found to be markedly elevated relative to that of the parent strain. These results are discussed in relation to the role of phosphorylation and relative DNA-binding affinity of OmpR in the expression of ompF and ompC. PMID- 1311296 TI - arcD, the first gene of the arc operon for anaerobic arginine catabolism in Pseudomonas aeruginosa, encodes an arginine-ornithine exchanger. AB - In the absence of oxygen and nitrate, Pseudomonas aeruginosa metabolizes arginine via the arginine deiminase pathway, which allows slow growth on rich media. The conversion of arginine to ornithine, CO2, and NH3 is coupled to the production of ATP from ADP. The enzymes of the arginine deiminase pathway are organized in the arcDABC operon. The arcD gene encodes a hydrophobic polytopic membrane protein. Translocation of arginine and ornithine in membrane vesicles derived from an Escherichia coli strain harboring a recombinant plasmid carrying the arcD gene was studied. Arginine and ornithine uptake was coupled to the proton motive force with a bias toward the transmembrane electrical potential. Accumulated ornithine was readily exchangeable for external arginine or lysine. The exchange was several orders of magnitude faster than proton motive force-driven transport. The ArcD protein was reconstituted in proteoliposomes after detergent solubilization of membrane vesicles. These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. It is concluded that the ArcD protein is a transport system that catalyzes an electroneutral exchange between arginine and ornithine to allow high-efficiency energy conversion in the arginine deiminase pathway. PMID- 1311297 TI - Site-specific deletion and rearrangement of integron insert genes catalyzed by the integron DNA integrase. AB - Deletion of individual antibiotic resistance genes found within the variable region of integrons is demonstrated. Evidence for gene duplications and rearrangements resulting from the insertion of gene units at new locations is also presented. Deletion, duplication, and rearrangement occur only in the presence of the integron-encoded DNA integrase. These events are precise and involve loss or gain of one or more complete insert units or gene cassettes. This confirms the recent definition of gene cassettes as consisting of the gene coding sequences, all except the last 7 bases of the 59-base element found at the 3' end of the gene, and the core site located 5' to the gene (Hall et al., Mol. Microbiol. 5:1941-1959, 1991) and demonstrates that individual gene cassettes are functional units which can be independently mobilized. Both deletions and duplications can be generated by integrase-mediated cointegrate formation followed by integrase-mediated resolution involving a different pair of sites. However, deletion occurs 10 times more frequently than duplication, and we propose that the majority of deletion events are likely to involve integrase dependent excision of the gene unit to generate a circular gene cassette. The implications of these findings in understanding the evolution of integrons and the spread of antibiotic resistance genes in bacterial populations is discussed. PMID- 1311298 TI - Nucleotide sequence of the Staphylococcus aureus gyrB-gyrA locus encoding the DNA gyrase A and B proteins. AB - We have determined the nucleotide sequence of a 5.3-kb segment of the Staphylococcus aureus chromosome that includes the gyrA and gyrB genes coding for both subunits of DNA gyrase, the enzyme that catalyzes ATP-dependent DNA supercoiling. The gene order at this locus, dnaA-dnaN-recF-gyrB-gyrA, is similar to that found in the Bacillus subtilis replication origin region. S. aureus recF, gyrB, and gyrA genes are closely spaced, occupy the same reading frame, and may be coordinately expressed. The S. aureus gyrB and gyrA genes encode 640- and 889 residue proteins, respectively, that share strong homology with other bacterial gyrase subunits, notably those from B. subtilis. These results are discussed in regard to the mechanism of DNA gyrase and its role as a target for the 4 quinolones and other antistaphylococcal agents. PMID- 1311299 TI - A BlnI restriction map of the Salmonella typhimurium LT2 genome. AB - BlnI or AvrII (5'-CCTAGG) sites are very rare in the Salmonella typhimurium LT2 genome. BlnI was used to construct a physical map which was correlated with the genetic map by using three methods. First, Tn10 carries BlnI sites, and the extra restriction sites produced by 34 genetically mapped Tn10 insertions were physically mapped by using pulsed-field gel electrophoresis. Second, six genetically mapped Mud-P22 prophage insertions were used to assign BlnI fragments. Integration of Mud-P22 introduces 30 kb of DNA that can easily be detected by a "shift up" in all but the largest BlnI fragments. Finally, induced Mud-P22 insertions package more than 100 kb of genomic DNA adjacent to one side of the insertion. Some of the smaller BlnI fragments were localized by hybridization to a dot blot array of 52 lysates from induced Mud-P22 insertions. Of the 10 BlnI sites mapped, 6 probably occur in or near the 16S rRNA genes at about 55, 71, 83, 86, 88.5, and 89.5 min. There is one BlnI site in the 90-kb pSLT plasmid. Two additional BlnI fragments of about 7 and 4 kb have not been localized. The size of the genome was estimated as 4.78 Mb (+/- 0.1 Mb) excluding pSLT but including prophages Fels-1 and Fels-2. One BlnI fragment that maps between 55 and 59 min showed a 40-kb reduction in size in a strain cured of the approximately 40-kb Fels-2 prophage. PMID- 1311300 TI - A physical map of the Salmonella typhimurium LT2 genome made by using XbaI analysis. AB - XbaI digestion and pulsed-field gel electrophoresis of the genome of Salmonella typhimurium LT2 yields 24 fragments: 23 fragments (total size, 4,807 kb) are from the chromosome, and one fragment (90 kb) is from the virulence plasmid pSLT. Some of the 23 fragments from the chromosome were located on the linkage map by the use of cloned genes as probes and by analysis of strains which gain an XbaI site from the insertion of Tn10. Twenty-one of the fragments were arranged as a circular physical map by the use of linking probes from a set of 41 lysogens in which Mud-P22 was stably inserted at different sites of the chromosome; fragment W (6.6 kb) and fragment X (6.4 kb) were not located on the physical map. XbaI digestion of strains with Tn10 insertions allowed the physical locations of specific genes along the chromosome to be determined on the basis of analysis of new-fragment sizes. There is good agreement between the order of genes on the linkage map, which is based primarily on P22 joint transduction and F-mediated conjugation, and the physical map, but there are frequently differences in the length of the interval from the two methods. These analyses allowed the measurement of the amount of DNA packaged in phage P22 heads by Mud-P22 lysogens following induction; this varies from ca. 100 kb (2 min) to 240 kb (5 min) in different parts of the chromosome. PMID- 1311301 TI - Rapid mapping in Salmonella typhimurium with Mud-P22 prophages. AB - A new method for mapping mutations in the Salmonella typhimurium chromosome is described and applied to the localization of novel regulatory mutations affecting expression of the nirB (nitrite reductase) gene. The mapping technique is also illustrated by the mapping of mutations in genes affecting carbohydrate catabolism and biosynthetic pathways. The new mapping method involves use of the hybrid phage MudP and MudQ (together referred to as Mud-P22), originally constructed by Youderian et al. (Genetics 118:581-592, 1988). This report describes a set of Mud-P22 lysogens, each member of the set containing a different Mud-P22 insertion. The insertions are scattered along the entire Salmonella genome. These lysogens, when induced by mitomycin C, generate transducing lysates that are enriched (45- to 1,400-fold over the background, generalized transducing particle population) for transducing particles containing bacterial DNA that flanks one side of the insertion. We demonstrate that within the set of lysogens there can be found at least one Mud-P22 insertion that enriches for any particular region of the Salmonella chromosome and that, therefore, all regions of the chromosome are discretely enriched and represented by the collection as a whole. We describe a technique that allows the rapid and facile determination of which lysate contains enriched sequences for the repair of a mutant locus, thereby allowing the determination of the map position of the locus. This technique is applicable to those mutations for which the wild-type allele is selectable. We also describe a procedure whereby any Tn10 insertion can be mapped by selecting for the loss of Tetr. PMID- 1311302 TI - Cloning and identification of the Escherichia coli murB DNA sequence, which encodes UDP-N-acetylenolpyruvoylglucosamine reductase. AB - The murB gene, which complemented the UDP-N-acetylenolpyruvoylglucosamine reductase (EC 1.1.1.158) mutation in Escherichia coli ST5, was cloned from an E. coli chromosomal library. murB was subcloned on a 2.8-kb PvuII fragment into pUC19 and sequenced. A 1,029-bp open reading frame encoded a 342-amino-acid polypeptide of 37,859 Da. A DNA sequence homology search revealed that murB had almost 100% homology with a previously reported unidentified open reading frame, ORFII, at 89.9 min. Physical and genetic mapping results were consistent with this map position, and minicell analyses of murB subclones showed a plasmid encoded protein of approximately 37,000 Da, which closely matched the calculated size of the murB protein. PMID- 1311303 TI - coaA and rts are allelic and located at kilobase 3532 on the Escherichia coli physical map. PMID- 1311304 TI - Tumor necrosis factor receptor signaling. A dominant negative mutation suppresses the activation of the 55-kDa tumor necrosis factor receptor. AB - To investigate the signaling mechanism of the 55-kDa tumor necrosis factor (TNF) receptor a functional transfection based assay was developed. The human 55-kDa TNF receptor, stably expressed in mouse L929 cells, was demonstrated to be activated specifically by agonist antibodies and to initiate a signal for cellular cytotoxicity. A deletion mutant of the human TNF receptor lacking most of the cytoplasmic domain was found to be completely defective in generating the signal for cytotoxicity. Additionally, expression of the truncated receptor substantially suppressed signaling by endogenous mouse TNF receptors in response to TNF, but not in response to specific anti-murine TNF receptor antibodies. These results suggest that aggregation of 55-kDa TNF receptor intracellular domains, which are not associated in the absence of ligand, is an important component of the signal for cellular toxicity. This work also provides an example of a dominant negative mutation in a transmembrane receptor that lacks a tyrosine kinase domain, and suggests a more general utility of dominant negative mutations in the investigation of cytokine receptor function. PMID- 1311305 TI - Autoanti-phosphatidylinositide antibodies specifically inhibit noradrenaline effects on Ca2+ and Cl- channels in rat portal vein myocytes. AB - High levels of circulating autoantibodies (auto-Ab) directed against phosphatidylinositides have been identified in the sera of patients with malignant tumors. These polyclonal autoantibodies had higher avidity and specificity for phosphatidylinositol (PtdIns) than for the other phosphatidylinositides. Effects of the auto-Ab were studied in smooth muscle myocytes in the PtdIns-involving transduction mechanism triggered by activation of alpha 1-adrenoceptors. Noradrenaline activated a Ca(2+)-dependent Cl- current through the Ca(2+)-releasing action of inositol 1,4,5-trisphosphate (InsP3) and enhanced the Ca2+ channel current through a diacylglycerol and protein kinase C dependent mechanism. External applications of auto-Ab (0.03-0.3 mg/ml) were without effect on noradrenaline-induced responses whereas intracellular applications (0.0004-0.012 mg/ml) inhibited both Cl- current activation and Ca2+ channel current stimulation. Intracellular applications of IgG from healthy donors had no effect on noradrenaline-induced responses. When anti-PtdIns Ab were preincubated with PtdIns the inhibition of the noradrenaline-induced responses on Ca2+ and Cl- channels was not observed. Autoanti-PtdIns Ab inhibited also the acetylcholine-activated Cl- current, confirming that the acetylcholine response was mediated through the phosphatidylinositol breakdown. In contrast, the autoanti-PtdIns Ab were ineffective against the transduction pathway after beta adrenoceptor activation. Therefore, these results suggest that the biological effect of autoanti-PtdIns Ab results from a specific binding to membrane PtdIns or PtdIns metabolites and thereby prevented InsP3 and diacylglycerol production. These autoanti-PtdIns Ab appear to be a new specific tool to identify the role of phosphatidylinositides in intracellular transduction processes. PMID- 1311306 TI - Regulation of purine nucleotide synthesis in human B lymphoblasts with both hypoxanthine-guanine phosphoribosyltransferase deficiency and phosphoribosylpyrophosphate synthetase superactivity. AB - Human B lymphoblast lines severely deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) were selected for resistance to 6-thioguanine from cloned normal and phosphoribosylpyrophosphate (PP-Rib-P) synthetase superactive cell lines and were compared with their respective parental cell lines with regard to growth and PP-Rib-P and purine nucleotide metabolism. During blockade of purine synthesis de novo with 6-methylthioinosine or aminopterin, inhibition of growth of all HGPRT-deficient cell lines was refractory to addition of Ade at concentrations which restored substantial growth to parental cell lines. Ade-resistant inhibition of growth of parental lines by 6 methylthioinosine, however, occurred during Ado deaminase inhibition. Insufficient generation of IMP (and ultimately guanylates) to support growth of lymphoblasts lacking HGPRT activity and blocked in purine synthesis de novo best explained these findings, implying that a major route of interconversion of AMP to IMP involves the reaction sequence: AMP----Ado----Ino----Hyp----IMP. PP-Rib-P generation and purine nucleoside triphosphate pools were unchanged by introduction of HGPRT deficiency into normal lymphoblast lines, in agreement with the view that accelerated purine synthesis de novo in this deficiency results from increased availability of PP-Rib-P for the pathway. Cell lines with dual enzyme defects did not differ from PP-Rib-P synthetase-superactive parental lines in rates of PP-Rib-P and purine synthesis despite 5-6-fold increases in PP-Rib-P concentrations, excretion of nearly 50% of newly synthesized purines, and diminished GTP concentrations. Fixed rates of purine synthesis de novo in PP-Rib P synthetase-superactive cells appeared to reflect saturation of the rate limiting amidophosphoribosyltransferase reaction for PP-Rib-P. In combination with accelerated purine excretion, increased channeling of newly formed purines into adenylates, and impaired conversion of AMP to IMP, fixed rates of purine synthesis de novo may condition cell lines with defects in HGPRT and PP-Rib-P synthetase to depletion of GTP with consequent growth retardation. PMID- 1311307 TI - Inositol tetrakisphosphate isomers and elevation of cytosolic Ca2+ in vasopressin stimulated insulin-secreting RINm5F cells. AB - Signal generation during the stimulation of insulin secretion by arginine vasopressin (AVP) was investigated in RINm5F cells. AVP (0.1 microM) caused a biphasic cytosolic Ca2+ ([Ca2+]i) rise, namely a rapid transient marked elevation after stimulation followed by a series of oscillations. In the absence of extracellular Ca2+, the sustained oscillations were abolished, while the initial [Ca2+]i transient was only partly decreased, indicating that the former are due to Ca2+ influx and the latter due mainly to mobilization from internal Ca2+ stores. AVP also evoked a transient depolarization of the average membrane potential. AVP-induced Ca2+ influx during the sustained phase, which was strictly dependent on receptor occupancy, was attenuated by membrane hyperpolarization with diazoxide. However, blockade of Ca2+ channels of the L- or T-type was ineffective. AVP stimulated production of diacylglycerol and inositol phosphates; for the latter both [3H] inositol labeling and mass determinations were performed. A transient increase in Ins(1,4,5)P3 was followed by a marked enhancement of Ins(1,3,4,5)P4 (8-fold) peaking at 15 s and gradually returning to basal values. Ins(1,3,4,6)P4 and Ins(3,4,5,6)P4 exhibited the most long-lasting augmentation (4- and 1.7-fold, respectively), and therefore correlated best with the period of sustained [Ca2+]i oscillations. InsP5 and InsP6 were not elevated. The effects of AVP, including the stimulation of insulin secretion from perifused cells, were obliterated by a V1 receptor antagonist. In conclusion, AVP induces protracted [Ca2+]i elevation in RINm5F cells which is associated with long lasting increases in InsP4 isomers. The accumulation of InsP4 isomers reflects receptor occupancy and accelerated metabolism of the inositol phosphates. Activation of second messenger-operated Ca2+ channels is not necessarily implicated because of the attenuating effect of membrane hyperpolarization. PMID- 1311308 TI - Site-directed mutagenesis in rat liver 6-phosphofructo-2-kinase. Mutation at the fructose 6-phosphate binding site affects phosphate activation. AB - To identify those residues involved in fructose 6-phosphate binding to the kinase domain of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase site directed mutations were engineered at Lys194, Arg195, Arg230, and Arg238. The mutant enzymes were purified to homogeneity by anion exchange and Blue-Sepharose chromatography and/or substrate elution from phosphocellulose columns. Circular dichroism experiments demonstrated that all of the single amino acid mutations had no effect on the secondary structure of the protein. In addition, when fructose-2,6-bisphosphatase activity was measured, all mutants had Km values for fructose 2,6-bisphosphate, Ki values for fructose 6-phosphate, and maximal velocities similar to that of the wild-type enzyme. Mutation of Arg195----Ala, or His, had little or no effect on the maximal velocity of the kinase but increased the Km for fructose 6-phosphate greater than 3,000-fold. Furthermore, the Ka for phosphate for Arg195Ala was increased 100-fold compared with the wild-type enzyme. Mutation of Lys194----Ala had no effect on maximal velocity or the Km for fructose 6-phosphate. Mutation of either Arg230 or Arg238----Ala increased the maximal velocity and the Km for fructose-6 phosphate of the kinase by 2-3-fold but had no effect on fructose-2,6-bisphosphatase. However, the Km values for ATP of the Arg230Ala and Arg238Ala mutants were 30-40-fold higher than that for the wild-type enzyme. Mutation of Gly48----Ala resulted in a form with no kinase activity, but fructose-2,6-bisphosphatase activity was identical to that of the wild-type enzyme. The results indicate that: 1) Arg195 is a critical residue for the binding of fructose 6-phosphate to the 6-phospho-fructo-2-kinase domain, and that interaction of the sugar phosphate with Arg195 is highly specific since mutation of the adjacent Lys194----Ala had no effect on fructose 6-phosphate binding; 2) Arg195 also play an important role in the binding of inorganic phosphate; and 3) Gly48 is an important residue in the nucleotide binding fold of 6-phosphofructo-2-kinase and that both Arg230 and Arg238 are also involved in ATP binding; and 4) the bifunctional enzyme has two separate and independent fructose 6-phosphate binding sites. PMID- 1311309 TI - A purified S6 kinase kinase from Xenopus eggs activates S6 kinase II and autophosphorylates on serine, threonine, and tyrosine residues. AB - S6 kinases I and II have been purified previously from Xenopus eggs and shown to be activated by phosphorylation on serine and threonine residues. An S6 kinase clone, closely related to S6 kinase II, was subsequently identified and the protein product was expressed in a baculovirus system. Using this protein, termed "rsk" for Ribosomal Protein S6 Kinase, as a substrate, we have purified to homogeneity from unfertilized Xenopus eggs a 41-kDa serine/threonine kinase termed rsk kinase. Both microtubule-associated protein-2 and myelin basic protein are good substrates for rsk kinase, whereas alpha-casein, histone H1, protamine, and phosvitin are not. rsk kinase is inhibited by low concentrations of heparin as well as by beta-glycerophosphate and calcium. Activation of rsk kinase during Xenopus oocyte maturation is correlated with phosphorylation on threonine and tyrosine residues. However, in vitro, rsk kinase undergoes autophosphorylation on serine, threonine, and tyrosine residues, identifying it as a "dual specificity" enzyme. Purified rsk kinase can be inactivated in vitro by either a 37-kDa T-cell protein-tyrosine phosphatase or the serine/threonine protein phosphatase 2A. Phosphatase-treated S6KII can be reactivated by rsk kinase, and S6 kinase activity in resting oocyte extracts increases significantly when purified rsk kinase is added. The availability of purified rsk kinase will enhance study of the signal transduction pathway(s) regulating phosphorylation of ribosomal protein S6 in Xenopus oocytes. PMID- 1311310 TI - Evidence for dual coupling of the murine luteinizing hormone receptor to adenylyl cyclase and phosphoinositide breakdown and Ca2+ mobilization. Studies with the cloned murine luteinizing hormone receptor expressed in L cells. AB - The murine receptor for luteinizing hormone (LHR) was cloned and expressed in L cells. This LHR (mature protein of 674 amino acids) is very similar to that of the rat (same length, 36 amino acid differences) but differs significantly more from that of man (673 amino acids, 109 differences). Expression of the murine LHR in L cells led to the appearance of binding sites for human chorionic gonadotropin (hCG) with a Kd of 150 pM and an LH- and hCG-stimulable adenylyl cyclase activity (EC50 = 50-100 pM hCG). Upon labeling pools of phosphoinositides with [3H]myo-inositol, L cells expressing the murine LHR responded to hCG with an increase in their rate of phosphoinositide hydrolysis (EC50 = 2,400 pM hCG). This was accompanied by an increase in intracellular Ca2+ [( Ca2+]i), as determined by the Fura2 method. This increase in [Ca2+]i in response to hCG was dependent on the LHR, for HCG did not affect [Ca2+]i in L cells not expressing the LHR. The effect was not due to the cAMP-forming activity of the LH receptor, for neither forskolin nor prostaglandin E1, which both increase cAMP levels in L cells, had a similar effect in either control or LHR-expressing cells and isoproterenol had no effect in L cells expressing a functionally active hamster beta-adrenergic receptor. The effect was also not due to overexpression of a Gs-coupled receptor, for L cells expressing 8-fold higher levels of the human V2 vasopressin receptor did not mimic the Ca(2+)-mobilizing response of the LH receptor. We conclude that the LH receptor has the capability of activating two intracellular signaling pathways: one leading to stimulation of adenylyl cyclase and resulting in increases in cAMP and a second leading to stimulation of phospholipase C and resulting in formation of inositol phosphates and elevations in [Ca2+]i. These data correlate positively with and provide a mechanistic explanation for previous reports on the ability of hCG to mobilize phosphoinositides and increasing [Ca2+]i in luteal and granulosa cells (e.g. Davis, J. S., West, L. A., and Farese, R. V. (1984) J. Biol. Chem. 259, 15028-15034). PMID- 1311312 TI - Activation and inhibition of ATP-sensitive K+ channels by fluorescein derivatives. AB - Fluorescein derivatives are known to bind to nucleotide-binding sites on transport ATPases. In this study, they have been used as ligands to nucleotide binding sites on ATP-sensitive K+ channels in insulinoma cells. Their effect on channel activity has been studied using 86Rb+ efflux and patch-clamp techniques. Fluorescein derivatives have two opposite effects. First, like ATP, they can inhibit active ATP-sensitive K+ channels. Second, they are able to reactivate ATP sensitive K+ channels subjected to inactivation or "run-down" in the absence of cytoplasmic ATP. Therefore reactivation of the inactivated ATP-sensitive K+ channel clearly does not require channel phosphorylation as is commonly believed. The results indicate the existence of two binding sites for nucleotides, one activator site and one inhibitor site. Irreversible binding at either the inhibitor or the activator site on the channel was obtained with eosin-5 maleimide, resulting in irreversible inhibition or activation of the ATP sensitive K+ channel respectively. The irreversibly activated channel could still be inhibited by 2 mM ATP. After activation by fluorescein derivatives, ATP sensitive K+ channels become resistant to the classical blocker of this channel, the sulfonylurea glibenclamide. Negative allosteric interactions between fluorescein/nucleotide receptors and sulfonylurea-binding sites were suggested by results obtained in [3H]glibenclamide-binding experiments. PMID- 1311311 TI - Direct spectroscopic evidence for the presence of a 6Fe cluster in an iron-sulfur protein isolated from Desulfovibrio desulfuricans (ATCC 27774) AB - A novel iron-sulfur protein was purified from the extract of Desulfovibrio desulfuricans (ATCC 27774) to homogeneity as judged by polyacrylamide gel electrophoresis. The purified protein is a monomer of 57 kDa molecular mass. It contains comparable amounts of iron and inorganic labile sulfur atoms and exhibits an optical spectrum typical of iron-sulfur proteins with maxima at 400, 305, and 280 nm. Mossbauer data of the as-isolated protein show two spectral components, a paramagnetic and a diamagnetic, of equal intensity. Detailed analysis of the paramagnetic component reveals six distinct antiferromagnetically coupled iron sites, providing direct spectroscopic evidence for the presence of a 6Fe cluster in this newly purified protein. One of the iron sites exhibits parameters (delta EQ = 2.67 +/- 0.03 mm/s and delta = 1.09 +/- 0.02 mm/s at 140 K) typical for high spin ferrous ion; the observed large isomer shift indicates an iron environment that is distinct from the tetrahedral sulfur coordination commonly observed for the iron atoms in iron-sulfur clusters and is consistent with a penta- or hexacoordination containing N and/or O ligands. The other five iron sites are most probably high spin ferric. Three of them show parameters characteristic for tetrahedral sulfur coordination. In correlation with the EPR spectrum of the as-purified protein which shows a resonance signal at g = 15.3 and a group of signals between g = 9.8 and 5.4, this 6Fe cluster is assigned to an unusual spin state of 9/2 with zero field splitting parameters D = -1.3 cm-1 and E/D = 0.062. Other EPR signals attributable to minor impurities are also observed at the g = 4.3 and 2.0 regions. The diamagnetic Mossbauer component represents a second iron cluster, which, upon reduction with dithionite, displays an intense S = 1/2 EPR signal with g values at 2.00, 1.83, and 1.31. In addition, an EPR signal of the S = 3/2 type is also observed for the dithionite-reduced protein. PMID- 1311313 TI - A metal ion-binding site in the kringle region of bovine prothrombin fragment 1. AB - 45Ca(II) binding studies (equilibrium dialysis) on the kringle domain of bovine prothrombin fragment 1 were conducted using a mixture of peptides (residues 43 156 and 46-156) resulting from limited alpha-chymotryptic hydrolysis of fragment 1. Analysis of the Scatchard plot of these data indicates a single, low affinity Ca(II)-binding site to be present. Similar results were obtained from studies on the decarboxylated fragment 1 derivative, 10-gamma-MGlu-fragment 1. Acetylation of bovine fragment 1 in the absence of Ca(II) or Mg(II) ions results in the loss of the metal ion-promoted quenching of the intrinsic Trp fluorescence of the protein and the Ca(II)-mediated binding to phosphatidylserine/phosphatidylcholine (PS/PC) vesicles. The acetylation of the NH2 alpha-group of Ala-1 has been shown (Welsch, D. J., and Nelsestuen, G. L. (1988) Biochemistry 27, 4946-4952) to abolish the PS/PC binding property of fragment 1. The present study demonstrates that acetylation of a second site possibly Ser-79 or Thr-81 using the conditions described in the preceding paper results in loss of both the fluorescence transition and the Ca(II)-mediated PS/PC binding of the resulting protein derivative. Removal of the O-acetyl group at the Ser-79/Thr-81 site is accomplished by aminolysis with 0.2 M hydroxylamine, pH 10, 50 degrees C; the fluorescence transition is partially restored. PS/PC binding is partially restored if the NH2 alpha-group of Ala-1 is trinitrophenylated but is not restored if the NH2 alpha-group of Ala-1 is acetylated. We conclude that the Ser 79/Thr-81 site may represent a portion of the metal ion-binding site within the kringle domain of fragment 1. Occupancy of this site by a Ca(II) ion appears to be important in the binding of the protein to PS/PC vesicles. PMID- 1311314 TI - Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. AB - Secreted metalloproteases initiating proteolytic degradation of collagens and proteoglycans play a critical role in remodeling of the connective tissue. Activation of the secreted proenzymes and interaction with their specific inhibitors TIMP and TIMP-2 are responsible for regulation of enzyme activity in extracellular space. We have previously demonstrated that 92- and 72-kDa Type IV procollagenases, in contrast to interstitial collagenase (ClI), form specific complexes with TIMP and the related inhibitor TIMP-2, respectively. The physiologic significance of the proenzyme-inhibitor complex and the mechanism of activation of Type IV collagenases remained unclear. Here, we demonstrate that in the absence of TIMP, 92-kDa Type IV procollagenase (92T4Cl) can form a covalent homodimer and a novel complex with ClI. In the presence of TIMP, the formation of a 92T4Cl proenzyme complex with TIMP prevents dimerization, formation of the complex with ClI, and activation of the 92T4Cl proenzyme by stromelysin, a related metalloprotease. The proenzyme homodimer is unable to form a complex with TIMP. All TIMP-free forms of the proenzyme can be activated by stromelysin. The 92T4Cl-ClI complex can be activated to yield a complex active against both gelatin and fibrillar Type I collagen, suggesting a mechanism for cooperative action of two enzymes in reducing collagen fibrils to small peptides under physiologic conditions. PMID- 1311315 TI - Difference in superoxide toxicity between 4,7-dicyanobenzofurazan and paraquat. AB - The O2-. production by aerobically cultured Escherichia coli in the presence of benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4 bromo-6-cyanobenzofurazan (4), and 4,7-dicyanobenzofurazan (5) was examined by using the cytochrome c reduction method in order to elucidate the mechanism of cytotoxicity of benzofurazans. Adding compound 5 to E. coli cell suspension caused cytochrome c reduction, which was completely inhibited by superoxide dismutase. The rate of cytochrome c reduction was in the order of 1 = 2 = 3 less than 4 less than 5, which correlates well with that of the reduction potentials of these benzofurazans. Adding glucose to the E. coli cell suspension-compound 5 cytochrome c system accelerated the rate of cytochrome c reduction. The formation of 4,7-dicyanobenzofurazan anion radical in the cell suspension-compound 5 glucose system in the absence of O2 was followed by ESR spectroscopy. The ESR signal of the anion radical disappeared when O2 was added. Compound 5 was shown to have an approximately 10-fold greater increasing effect on the flux of O2-. by E. coli than paraquat (PQ) by the cytochrome c reduction method. The results were confirmed by the electrochemical method with an oxygen electrode. However, compound 5 had a bacteriostatic, but not lethal, effect, while PQ had both effects. The effect of compound 5 and PQ on lethality of E. coli showed a dramatic difference when E. coli was exposed to these two compounds and washed prior to testing the effects of that exposure. This difference probably arose because compound 5 readily leaked from the cells during dilution and plating. Also, the reduced form of compound 5 exits from the cells more readily than the reduced form of PQ and then generates O2-. in the medium by autoxidation. This suggests the importance of the intracellular production of O2-., rather than the extracellular production of O2-., for lethal effect. PMID- 1311316 TI - Identification of cis- and trans-acting factors regulating the expression of the human insulin receptor gene. AB - The functional organization of the human insulin receptor (hIR) promoter was analyzed by deletion mutagenesis and protein-DNA interaction studies. A series of deletion mutants was expressed transiently in two human hepatocytes, HepG2 and PLC. The results revealed that the promoter region between -692 and -345 is essential for efficient transcription of the hIR gene. Multiple trans-acting factors were identified by band shift and footprinting analyses. Sp1 binds to a cluster of GC boxes and two GGGAGG hexamers locating at -637 to -594. Adjacent to GC boxes, there are two regions, from -550 to -530 and from -522 to -503, which bind to two novel factors, IRNF-I and IRNF-II. These two factors are distributed differentially in different cell lines. Linker scanning mutations on GC, GA boxes, or the IRNF-I binding site significantly decreased the transcriptional activity, indicating that IRNF-I and Sp1 are important for hIR promoter activity. In addition, we demonstrated that glucocorticoid-dependent transcriptional induction of hIR mRNA in vivo is conferred by a glucocorticoid response element in the hIR promoter. Taken together, these results imply that transcription of the human insulin receptor gene is regulated by multiple protein-DNA interactions occurring within the defined promoter region. PMID- 1311317 TI - Activated phosphoinositide 3-kinase associates with membrane skeleton in thrombin exposed platelets. AB - Human platelets undergo a rapid, major reorganization of the cytoskeletal matrix upon exposure to thrombin, and accumulate 3-phosphorylated phosphoinositides in a protein kinase C (PKC)-dependent manner. These phosphoinositides have been suggested to be involved in actin polymerization/depolymerization. We reasoned that, if newly generated 3-phosphorylated phosphoinositide modulates cytoskeletal reorganization, a prerequisite for such action would be generation near cytoskeletal proteins. We have found that, after platelet activation, phosphatidylinositol 3-kinase and phosphatidylinositol(4)P 3-kinase activities, antibody-detectable phosphoinositide 3-kinase, and PKC become markedly and specifically enriched in a Triton X-100-insoluble cytoskeletal fraction that contains GPIIb/IIIa (integrin) and pp60c-src. The cytoskeletal fraction then accounts for up to 70% of total phosphoinositide 3-kinase activity, a function of recruited activated enzyme. These proteins are not occluded or directly associated with newly polymerized actin, since blockage by cytochalasin D of actin polymerization, and consequent inhibition of accumulation of about 40% of incremental protein and actin in this fraction, has no effect on its content of phosphoinositide 3-kinase, GPIIb/IIIa, pp60c-src, or PKC. Depolymerization of actin with DNase I, or inhibition of ligand binding to GPIIb/IIIa by RGDS, however, in combination with cytochalasin D, further depletes actin and significantly decreases sedimentability of GPIIb/IIIa as well as phosphoinositide 3-kinase, pp60c-src, and PKC, without inhibiting total 3-kinase activity. Our results suggest that, as a function of platelet activation, enzymes that regulate the synthesis of 3-phosphorylated phosphoinositides rapidly associate with the membrane skeleton and that skeletally associated phosphoinositide 3-kinase is more active than the Triton-soluble form. PMID- 1311318 TI - Sites in the third intracellular loop of the alpha 2A-adrenergic receptor confer short term agonist-promoted desensitization. Evidence for a receptor kinase mediated mechanism. AB - To investigate the mechanisms of agonist-promoted desensitization of the alpha 2 adrenergic receptor (alpha 2AR), the human alpha 2AAR and a mutated form of the receptor were expressed in CHW cells. After cells were exposed to epinephrine for 30 min, the ability of the wild type alpha 2AAR to mediate inhibition of forskolin-stimulated adenylyl cyclase was depressed by approximately 78%. To assess the role of receptor phosphorylation during desensitization, cells were incubated with 32Pi, exposed to agonist, and alpha 2AAR purified by immunoprecipitation with a fusion protein antibody. Agonist-promoted desensitization was found to be accompanied by phosphorylation of the alpha 2AAR in vivo. The beta-adrenergic receptor kinase (beta ARK) is known to phosphorylate purified alpha 2AAR in vitro. We found that heparin, a beta ARK inhibitor, ablated short term agonist-induced desensitization of alpha 2AAR, while such desensitization was unaffected by inhibition of protein kinase A. To further assess the role of beta ARK, we constructed a mutated alpha 2AAR which has a portion of the third intracellular loop containing 9 serines and threonines (potential phosphorylation sites) deleted. This mutated alpha 2AAR failed to undergo short term agonist-induced desensitization. Agonist promoted in vivo phosphorylation of this mutated receptor was reduced by 90%, consistent with the notion that receptor phosphorylation at sites in the third intracellular loop plays a critical role in alpha 2AAR desensitization. After 24 h of agonist exposure, an even more profound desensitization of alpha 2AAR occurred, which was not accompanied by a decrease in receptor expression. Rather, long term agonist induced desensitization was found to be due in part to a decrease in the amount of cellular Gi, which was not dependent on receptor third loop phosphorylation sites. PMID- 1311319 TI - Purified epithelial Na+ channel complex contains the pertussis toxin-sensitive G alpha i-3 protein. AB - We have recently demonstrated that the amiloride-sensitive Na+ channel in the apical membrane of the renal epithelial cell line, A6, is modulated by the alpha i-3 subunit of the Gi-3 protein. We also showed that a 700-kDa protein complex can be purified from the membranes of A6 epithelia which (a) can reconstitute the amiloride-sensitive Na+ influx in liposomes and planar bilayer membranes and (b) consists of six major protein bands observed on reducing sodium dodecyl sulfate polyacrylamide gels with molecular masses ranging from 35 to 320 kDa. The present study was undertaken to determine if the alpha i-3 subunit was a member of this Na+ channel complex. G alpha i structure and function were identified by Western blotting with specific G alpha i subunit antibodies and Na+ channel antibodies, through ADP-ribosylation with pertussis toxin, and by immunocytochemical localization of the Na+ channel and G alpha i proteins. We demonstrate that two protein substrates are ADP-ribosylated in the 700-kDa complex in the presence of pertussis toxin and are specifically immunoprecipitated with an anti-Na+ channel polyclonal antibody. One of these substrates, a 41-kDa protein, was identified as the alpha i-3 subunit of the Gi-3 protein on Western blots with specific antibodies. Na+ channel antibodies do not recognize G alpha i-3 on Western blots of Golgi membranes which contain alpha i-3 but not Na+ channel proteins, nor do they immunoprecipitate alpha i-3 from solubilized Golgi membranes; however, alpha i-3 is coprecipitated as part of the Na+ channel complex from A6 cell membranes by polyclonal Na+ channel antibodies. Both alpha i-3 and the Na+ channel have been localized in A6 cells by confocal imaging and immunofluorescence with specific antibodies and are found to be in distinct but adjacent domains of the apical cell surface. In functional studies, alpha i-3, but not alpha i-2, stimulates Na+ channel activity. These data are therefore consistent with the localization of Na+ channel activity and modulatory alpha i-3 protein at the apical plasma membrane, which together represent a specific signal transduction pathway for ion channel regulation. PMID- 1311320 TI - Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin. AB - Some strains of Staphylococcus aureus bind collagen with a high degree of specificity and affinity. This interaction can represent a mechanism of substrate adhesion and may be an important step in the pathogenesis of osteomyelitis and infectious arthritis. We now report on the cloning, sequencing, and expression of a gene name cna, encoding a S. aureus collagen adhesin. The cna gene was isolated from a lambda GT11 S. aureus genomic library and encodes an 1185 amino acid polypeptide. The deduced amino acid sequence reveals several structural characteristics similar to previously described Gram-positive bacterial cell surface proteins. Antibodies raised against the native collagen adhesin from S. aureus recognize the recombinant collagen adhesin. Collagen binding activity can be detected in a lysate obtained from Escherichia coli cells, which harbor the cloned cna gene on an expression plasmid. Collagen-binding proteins can be detected in the lysate when analyzed by a Western blot type assay in which the membrane-transferred proteins are probed with radioactively labeled collagen. Finally, the bacterial lysate containing the recombinant adhesin can effectively inhibit the binding of soluble collagen to cells of S. aureus. PMID- 1311321 TI - Identification of MRF4, myogenin, and E12 oligomer complexes by chemical cross linking and two-dimensional gel electrophoresis. AB - The muscle-specific regulatory factors MRF4 and myogenin, as well as the ubiquitous factor E12, belong to a protein family which shares a common structural motif referred to as the basic helix-loop-helix domain. Recent studies have demonstrated that MRF4 and myogenin, in the presence of E12, bind efficiently to enhancer regions of muscle-specific genes, thereby activating their transcription. Although several lines of evidence suggest that MRF4 and E12 or myogenin and E12 hetero-oligomers exist, direct studies revealing the composition of these protein complexes have not been reported. Here, we demonstrate that MRF4 and myogenin preferentially form heterodimers with E12 in solution and that heterodimer formation in vitro is greatly enhanced when the two proteins are co-synthesized. Utilizing a novel two-dimensional gel electrophoresis system, we have found that MRF4 and myogenin, when complexed with E12, bind as heterodimers to the E-box consensus sequences associated with the troponin I, M-creatine kinase, and myosin light chain gene enhancers. In all cases, higher order oligomer structures were not detected, demonstrating that in vitro DNA binding abilities of these basic helix-loop-helix proteins require heterodimer formation. PMID- 1311322 TI - In situ kinetic parameters of glucose-6-phosphatase in the rat liver lobulus. AB - Glucose-6-phosphatase activity has been determined in periportal and pericentral zones of the rat liver lobule using a quantitative histochemical method. The study was performed on unfixed cryostat sections of livers from fasted and fed female and male rats. Highest activity was found in periportal zones, and starvation caused a 2-3-fold increase of glucose-6-phosphatase activity in periportal and pericentral zones of both sexes. Unexpectedly, KM values were also significantly different in periportal and pericentral zones and were found to increase linearly with Vmax values, irrespective of sex and feeding condition. Because the cryofixation procedure was shown to permeabilize the biomembranes in the tissue sections, it can be concluded that the rise in KM and Vmax values has to be attributed to the catalytic unit of the glucose-6-phosphatase system. It is suggested that the enzyme exists in a high affinity configuration at low enzyme concentrations but that at high enzyme concentrations a hysteretic mechanism, as proposed by Berteloot et al. (Berteloot, A., Vidal, H., and Van de Werve, G. (1991) J. Biol. Chem. 266, 5497-5507), transforms the enzyme from a high to a low affinity configuration. The present study indicates that the concept of functional heterogeneity of liver parenchyma may be more complex than thus far assumed. PMID- 1311323 TI - Preparation of a phospholipid-insensitive, autophosphorylation-activated catalytic fragment of Acanthamoeba myosin I heavy chain kinase. AB - The actin-activated Mg(2+)-ATPase activity of Acanthamoeba myosin I depends on phosphorylation of its single heavy chain. The activity of the myosin I heavy chain kinase is increased about 50-fold by autophosphorylation, and the rate of kinase autophosphorylation is enhanced about 20-fold by acidic phospholipids independent of the presence of Ca2+ (Brzeska, H., Lynch, T. J., and Korn, E. D. (1990) J. Biol. Chem. 265, 3591-3594). In this paper, we show that chymotryptic digestion of the kinase produces a 54-kDa fragment which contains three to four of the approximately 11 original phosphorylation sites and whose activity is greatly stimulated by autophosphorylation. However, both the rate of autophosphorylation and the kinase activity of the 54-kDa fragment are independent of phospholipid and comparable to those of intact kinase in the presence of phospholipid. These data imply that the (probably NH2-terminal) region(s) removed by proteolysis is necessary for phospholipid-sensitive inhibition of autophosphorylation of sites residing within the (probably COOH terminal) 54-kDa fragment. The 54-kDa fragment contains the catalytic site of the kinase as well as three to four sites whose phosphorylation is necessary for full expression of kinase activity. The middle region of the kinase molecule contains proline-rich regions that are similar to the COOH-terminal tail of the kinase substrate, Acanthamoeba myosin I. PMID- 1311324 TI - Development regulation of the subcellular distribution and glycosylation of GLUT1 and GLUT4 glucose transporters during myogenesis of L6 muscle cells. AB - L6 myoblasts spontaneously undergo differentiation and cell fusion into myotubes. These cells express both GLUT1 and GLUT4 glucose transporters, but their expression varies during myogenesis. We now report that the subcellular distribution and the protein processing by glycosylation of both glucose transporter isoforms also change during myogenesis. Crude plasma membrane and light microsome fractions were isolated from either myoblasts or myotubes and characterized by the presence of two functional proteins, the Na+/K(+)-ATPase and the dihydropyridine receptor (DHPR). Immunoreactive alpha 1 subunit of the Na+/K(+)-ATPase was faint in the crude plasma membrane fraction from myoblasts, but abundant in both membrane fractions from myotubes. In contrast, the alpha 1 subunit of the DHPR, which is expressed only in differentiated muscle, was detected in crude plasma membrane from myotubes but not from myoblasts. Therefore, crude plasma membrane fractions from myoblasts and myotubes contain cell surface markers, and the composition of these membranes appears to be developmentally regulated during myogenesis. GLUT1 protein was more abundant in the crude plasma membrane relative to the light microsome fraction prepared from either myoblasts or myotubes. The molecular size in sodium dodecyl sulfate polyacrylamide gel electrophoresis of the GLUT1 transporters in myotubes was smaller than that in myoblasts (Mr 47,000 and 53,000, respectively). GLUT4 protein (Mr 48,000) was barely detectable in the crude plasma membrane fraction and was almost absent in the light microsome fraction prepared from myoblasts. However, GLUT4 protein was abundant in myotubes and was predominantly located in the light microsome fraction. Treatment with endoglycosidase F reduced the molecular size of the transporters in all fractions to Mr 46,000 for GLUT1 and Mr 47,000 for GLUT4 proteins. In myotubes, acute insulin treatment increased the crude plasma membrane content of GLUT1 marginally and of GLUT4 markedly, with a concomitant decrease in the light microsomal fraction. These results indicate that: (a) the subcellular distribution of glucose transporters is regulated during myogenesis, GLUT4 being preferentially sorted to intracellular membranes; (b) both GLUT1 and GLUT4 transporters are processed by N-linked glycosylation to form the mature transporters in the course of myogenesis; and (c) insulin causes modest recruitment of GLUT1 transporters and marked recruitment of GLUT4 transporters, from light microsomes to plasma membranes in L6 myotubes. PMID- 1311325 TI - Cardiac-specific phosphorylation site for multifunctional Ca2+/calmodulin dependent protein kinase is conserved in the brain ryanodine receptor. AB - An antiserum raised against the region of the cardiac ryanodine receptor (residues 2805-2819) containing the phosphorylation site for multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) was used to identify the brain ryanodine receptor. This antiserum, which is cardiac isoform-specific, immunoprecipitated greater than 90% of the [3H]ryanodine receptor binding sites solubilized from guinea pig brain membranes. The immunoprecipitated brain receptor exhibited the characteristic cardiac-type mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The brain ryanodine receptor, like the cardiac ryanodine receptor, was a substrate for CaM kinase. Affinity purified, site-specific antibodies completely blocked phosphorylation of both brain and cardiac receptors by CaM kinase, and two-dimensional peptide mapping identified the same major 32P-labeled peptide in receptors from both tissues. 125I-Labeled receptors also gave the same peptide maps. These results confirm that mammalian brain expresses the cardiac isoform of the ryanodine receptor. Furthermore, the unique CaM kinase phosphorylation site, which has been shown to regulate Ca2+ channel activity, is conserved. PMID- 1311326 TI - The RecB subunit of the Escherichia coli RecBCD enzyme couples ATP hydrolysis to DNA unwinding. AB - The RecB subunit of the Escherichia coli RecBCD enzyme has previously been reported to possess DNA-dependent ATPase activity (Hickson, I. D., Robson, C. N., Atkinson, K. E., Hutton, L., and Emmerson, P. T. (1985) J. Biol. Chem. 260, 1224 1229). Here we demonstrate that a specific interaction between RecB protein and ATP can also be shown by photoaffinity labeling with the ATP analogue 8-azido ATP. Furthermore, the capacity of the RecB protein to support ATP hydrolysis varies with the structure and length of the DNA cofactor. Single-stranded linear and circular DNA are markedly better in promoting ATP hydrolysis than duplex DNA. The purified RecB protein can function as a DNA helicase, displacing oligonucleotides annealed to viral M13 DNA in an ATP-dependent and orientation specific manner. PMID- 1311327 TI - Proteolytic inactivation of alpha 1-proteinase inhibitor and alpha 1 antichymotrypsin by oxidatively activated human neutrophil metalloproteinases. AB - Human neutrophils use the H2O2-myeloperoxidase-chloride system to generate chlorinated oxidants capable of activating metalloproteinase zymogens that hydrolyze not only native and denatured collagens, but also the serine proteinase inhibitor (serpin) alpha 1-proteinase inhibitor (alpha 1 PI). To identify the metalloenzyme that hydrolyzes and inactivates alpha 1 PI, neutrophil releasates were chromatographed over gelatin-Sepharose and divided into fractions containing either progelatinase or procollagenase. The gelatinase-containing fraction cleaved alpha 1 PI in a manner inhibitable by native type V, but not type I, collagen. Conversely, while the collagenase-containing fraction also cleaved alpha 1 PI, this activity was inhibited by type I, but not type V, collagen. Because type I and V collagens are competitive substrates for collagenase and gelatinase, respectively, each of the metalloproteinase zymogens were purified to apparent homogeneity and examined for alpha 1 PI-hydrolytic activities. Both purified gelatinase and collagenase inactivated alpha 1PI by hydrolyzing the serpin within its active-site loop at the Phe352-Leu353 and Pro357-Met358 bonds, albeit with distinct kinetic properties. Furthermore, purified collagenase, but not gelatinase, cleaved a second serpin, alpha 1-antichymotrypsin, by hydrolyzing the Ala362-Leu363 bond within its active-site loop. These data demonstrate that human neutrophils use chlorinated oxidants to activate collagenolytic metalloproteinases whose substrate specificities can be extended to members of the serpin superfamily. PMID- 1311328 TI - Serotonin increases the cAMP concentration and the phosphoenolpyruvate carboxykinase mRNA in rat kidney, small intestine, and liver. AB - Within 60 min of the administration of serotonin to fasted-refed rats, there was a 5-, 16-, and 20-fold stimulation of the mRNA coding for the cytosolic form of P enolpyruvate carboxykinase in the kidney, small intestine and liver, respectively. This stimulation was 5-, 1.3-, and 2-fold higher than noted in the same tissue after 24 h of starvation. Dose- and time-response curves to serotonin in the three tissues were similar. The level of PEPCK mRNA in the liver was significantly elevated within 30 min of serotonin administration, whereas 60 min was required in the small intestine and the kidney. The direct effect of serotonin on PEPCK mRNA was also assessed in hepatocytes maintained in primary culture. Serotonin (10(-8) M to 10(-4) M) caused a dose-dependent increase in the level of PEPCK mRNA and a transient increase in cAMP concentration. Within the first min of serotonin (10(-6) M) addition to cells, cAMP concentration increased 4-fold and returned after 10 min to basal level. Therefore, these results provide functional evidence of serotonin action in the rat peripheric tissues and suggest that cAMP is involved in its intracellular signalling. PMID- 1311329 TI - Treatment of myeloid leukemic cells with the phosphatase inhibitor okadaic acid induces cell cycle arrest at either G1/S or G2/M depending on dose. AB - The phosphatase inhibitor okadaic acid was found to induce cell cycle arrest of human myeloid leukemic cell lines HL-60 and U937 in a concentration- and time dependent manner. Exposure to low concentrations of okadaic acid (2-8nM) for 24 48 hr caused greater than 70% of cells to arrest at G2/M, with up to 40% of the cells arrested in early mitosis. Cell viability decreased rapidly after 48 hr of treatment, and morphological and DNA structure analysis indicated that this was primarily due to the induction of apoptosis. The cells arrested in mitosis by 8 nM okadaic acid could be highly enriched by density gradient centrifugation and underwent apoptosis when further cultured either with or without okadaic acid, indicating that the effects of okadaic acid were irreversible. In contrast to the effects of low concentrations of okadaic acid, high concentrations (500 nM), inhibited proliferation in less than 3 hr. Remarkably, the majority of cells also entered a mitosis-like state characterized by dissolution of the nuclear membrane and condensation and partial separation of chromosomes. However, these cells had a diploid content of DNA, indicating that the cell cycle arrest occurred at G1/S with premature chromosome condensation (PCC), rather than at G2/M. If cells were first blocked at G1/S with hydroxyurea and then treated with okadaic acid, greater than 90% developed PCC in less than 3 hr without replicating their DNA. Caffeine was not able to induce PCC in these cells, either with or without prior inhibition of DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311330 TI - Identification of estrogen receptor mRNA and the estrogen modulation of parathyroid hormone-stimulated cyclic AMP accumulation in opossum kidney cells. AB - The opossum kidney (OK) cell was used as a model to test the hypothesis that estrogen directly affects proximal renal tubular epithelial cells. To demonstrate the expression of estrogen receptor in OK cells, we developed an approach using reverse transcription and the polymerase chain reaction. Analysis of the DNA amplified with nested primers revealed the predicted size fragment and restriction enzyme digestion products. To demonstrate the functional effects of estrogen, OK cells at confluence were preincubated in serum-free medium for 7-10 days with or without 17 beta-estradiol. Bovine PTH(1-34) (bPTH(1-34)) then stimulated a dose-dependent intracellular accumulation of cAMP that was maximal after 1 min and then gradually declined. Cyclic AMP in the medium slowly increased over 60 min. Preincubation with 17 beta-estradiol did not affect cell proliferation as measured by total protein content but caused an inhibition of bPTH(1-34)-stimulated intracellular cAMP accumulation that was maximal at 10(-11) M 17 beta-estradiol (71 +/- 3% control, p less than .001). bPTH(1-34) also increased cAMP release into the medium, an effect maximal using 10(-10) M 17 beta estradiol (118 +/- 3% control, p less than .001). Preincubation with the inactive isomer 17 alpha-estradiol caused no changes in cAMP accumulation or release. Coincubation with the antiestrogen tamoxifen blocked the effects of 17 beta estradiol. Sodium-dependent phosphate transport was: (1) inhibited by 2-h incubations with 10(-8) or 10(-10) M bPTH(1-34) and not affected by preincubation with 17 beta-estradiol, and (2) not inhibited by a 20-min incubation with 10(-8) M bPTH(1-34) unless cells were preincubated with 10(-8) M 17 beta-estradiol, suggesting that any possible effects of estrogen on phosphate transport are not directly mediated by changes in cAMP. These studies demonstrate the presence of estrogen receptor mRNA in OK cells as well as direct and specific effects of physiologic concentrations of estrogen on cAMP accumulation in these cells. This system may be a good model for further study of estrogen and PTH effects on the kidney. PMID- 1311331 TI - Epidermal growth factor stimulates cAMP accumulation in cultured rat cardiac myocytes. AB - We have previously shown that epidermal growth factor (EGF) augments cAMP accumulation in the heart and stimulates cardiac adenylyl cyclase via a G protein mediated mechanism (Nair et al., 1989). More recently, employing an antibody against the carboxy-terminus decapeptide of Gs alpha, we have demonstrated that Gs alpha mediates the effects of EGF on cardiac adenylyl cyclase (Nair et al., 1990). Since the heart comprises of a variety of cell types, the purpose of the studies presented here was to determine whether or not the effects of EGF on adenylyl cyclase were mediated in cardiac myocytes or noncardiomyocytes. Therefore, cultures of ventricular cardiomyocytes and noncardiomyocytes from neonatal rat hearts were established and characterized. Apart from the differences in cellular morphology, cardiomyocytes but not the noncardiomyocytes employed in our studies expressed the alpha- and beta-myosin heavy chain (MHC) mRNA and the beta-MHC protein. Additionally, as described previously, treatment of cardiomyocytes with thyroid hormone increased alpha-MHC mRNA and decreased the expression of beta-MHC mRNA, indicating that the cardiomyocytes employed in our studies were responding in a physiologically relevant manner. EGF in a time dependent manner increased cAMP accumulation in the cardiomyocytes but not in noncardiomyocytes. Maximum and half-maximum effects were observed at 100 nM and 2 nM concentrations of EGF, respectively. As determined by the presence of immunoreactive EGF receptors and tyrosine phosphorylation of the 170 kDa protein in membranes of cardiomyocytes and noncardiomyocytes, both the cell populations contained functional EGF receptors. Therefore, the differential effects of EGF on cAMP accumulation in the two cell populations appear to be due to differential coupling of the EGF receptors to the adenylyl cyclase system rather than the absence of EGF receptors in noncardiomyocytes. Consistent with our previous findings in isolated membranes and perfused rat hearts, EGF-elicited increase in cAMP accumulation in cardiomyocytes did not involve activation of beta adrenoreceptors and was abolished by prior treatment of cells with cholera toxin. Overall, our findings demonstrate that EGF-elicited increase in cAMP accumulation in the heart is the reflection of changes in cAMP content of cardiomyocytes and not noncardiomyocytes. PMID- 1311333 TI - Cyclic AMP potentiates bFGF-induced neurite outgrowth in PC12 cells. AB - We report here that basic fibroblast growth factor (bFGF)-elicited neurite outgrowth in PC12 cells is potentiated by dibutyryl cyclic adenosine monophosphate (dbcAMP) or forskolin. This property was also described for nerve growth factor (NGF), suggesting that both NGF and bFGF may share common intracellular events leading to neurite outgrowth and synergism with dbcAMP and forskolin. The synergistic effect of dbcAMP and forskolin is specific, since treatment of PC12 cells with bFGF and dibutyryl cyclic guanosine monophosphate (dbcGMP) or phorbol ester did not change the neurite outgrowth response of cells treated with bFGF alone. Furthermore, neurite outgrowth depends on cellular adhesion. Increasing adhesion by plate treatment with poly-d-lysine increases the neurite outgrowth elicited by bFGF alone or bFGF plus dbcAMP. On the other hand, decreasing cellular adhesiveness by plating PC12 cells in semi-solid agarose renders the cells unable to develop neuritic processes. In addition, 3H methylthymidine incorporation studies showed that bFGF-treated PC12 cells cease growth only when they become fully differentiated after 3-5 days of treatment. In contrast, dbcAMP, which is a poor differentiation factor, is able to block cellular growth after 24 hour treatment. These results suggest that when PC12 cells become differentiated, they stop growing. However, growth inhibition does not necessarily lead to differentiation. PMID- 1311332 TI - Tunicamycin reduces Na(+)-K(+)-pump expression in cultured skeletal muscle. AB - The purpose of this study was to examine effects of tunicamycin (TM), which inhibits core glycosylation of the beta-subunit, on functional expression of the Na(+)-K+ pump in primary cultures of embryonic chick skeletal muscle. Measurements were made of specific-[3H]-ouabain binding, ouabain-sensitive 86Rb uptake, resting membrane potential (Em), and electrogenic pump contribution to Em (Ep) of single myotubes with intracellular microelectrodes. Growth of 4-6-day-old skeletal myotubes in the presence of TM (1 microgram/ml) for 21-24 hr reduced the number of Na(+)-K+ pumps to 60-90% of control. Na(+)-K+ pump activity, the level of resting Em and Ep were also reduced significantly by TM. In addition, TM completely blocked the hyperpolarization of Em induced in single myotubes by cooling to 10 degrees C and then re-warming to 37 degrees C. Effects of tunicamycin were compared with those of tetrodotoxin (TTX; 2 x 10(-7) M for 24 hr), which blocks voltage-dependent Na+ channels. TM produced significantly greater decreases in ouabain-binding and Em than did TTX, findings that indicate that reduced Na(+)-K+ pump expression was not exclusively secondary to decreased intracellular Na+, the primary regulator of pump synthesis in cultured muscle. Similarly, effects of TM were significantly greater than those of cycloheximide, which inhibits protein synthesis by 95%. These findings demonstrate that effects were not due to inhibition of protein synthesis. We conclude that glycosylation of the Na(+)-K+ pump beta-subunit is required for full physiological expression of pump activity in skeletal muscle. PMID- 1311334 TI - Characterization of pseudorabies virus antibody responses in young swine after infection and vaccination by using an immunoglobulin M antibody capture enzyme linked immunosorbent assay. AB - An immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MACELISA) was developed for the detection of pseudorabies virus (PRV)-specific IgM antibody in swine sera because false-positive reactions frequently occurred when sera from older swine were tested with an indirect IgM enzyme-linked immunosorbent assay. Monoclonal mouse anti-swine IgM was used as the capturing antibody, and rabbit anti-PRV hyperimmune gamma globulin was used as the indicating antibody. Sera from non-PRV-infected, experimentally infected, vaccinated and challenged, passively immune and challenged, and naturally infected swine were evaluated. The PRV MACELISA had a specificity of 95% and was as sensitive and reproducible as previously reported in direct assays. An antibody response was still detectable with the MACELISA 21 days after inoculation. The PRV MACELISA did not detect a consistent antibody response in sera from swine vaccinated with either killed-PRV or modified live-virus vaccines but did detect an antibody response in sera from passively immune pigs after challenge with virulent PRV. These results indicated that the PRV MACELISA may be useful for the rapid serodiagnosis of recent PRV infection in swine. PMID- 1311335 TI - Comparison of the benzoyl-DL-arginine-naphthylamide (BANA) test, DNA probes, and immunological reagents for ability to detect anaerobic periodontal infections due to Porphyromonas gingivalis, Treponema denticola, and Bacteroides forsythus. AB - Most forms of periodontal disease are associated with the presence or overgrowth of anaerobic species that could include Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus among others. These three organisms are among the few cultivable plaque species that can hydrolyze the synthetic trypsin substrate benzoyl-DL-arginine-naphthylamide (BANA). In turn, BANA hydrolysis by the plaque can be associated with periodontal morbidity and with the presence of these three BANA-positive organisms in the plaque. In this investigation, the results of the BANA test, which simultaneously detects one or more of these organisms, were compared with the detection of these organisms by (i) highly specific antibodies to P. gingivalis, T. denticola, and B. forsythus; (ii) whole genomic DNA probes to P. gingivalis and T. denticola; and (iii) culturing or microscopic procedures. The BANA test, the DNA probes, and an enzyme-linked immunosorbent assay or an indirect immunofluorescence assay procedure exhibited high sensitivities, i.e., 90 ot 96%, and high accuracies, i.e., 83 to 92%, in their ability to detect combinations of these organisms in over 200 subgingival plaque samples taken from the most periodontally diseased sites in 67 patients. This indicated that if P. gingivalis, T. denticola, and B. forsythus are appropriate marker organisms for an anaerobic periodontal infection, then the three detection methods are equally accurate in their ability to diagnose this infection. The same statement could not be made for the culturing approach, where accuracies of 50 to 62% were observed. PMID- 1311336 TI - In vitro transcription and translation of group B rotavirus strain IDIR gene 8 and immunoprecipitation by human sera. AB - Group B rotaviruses (GBRs) are associated with episodes of acute diarrhea in humans and a variety of animal species. To date, these agents have not been well adapted to growth in tissue culture, and evaluation of human sera for antibodies directed against GBRs has been hindered by the inability to obtain standardized and highly purified preparations of GBR antigens. In order to evaluate the reactivities of antisera with a highly specific antigen, we prepared a full length cDNA clone of gene 8 of the IDIR strain of GBR. This clone was transcribed with T7 RNA polymerase, and the resulting RNA was translated in vitro with rabbit erythrocyte lysates. The polypeptide expressed from IDIR gene 8 was specifically precipitated by antibody directed against IDIR but not by antibody directed against ADRV (adult diarrhea rotavirus) or bovine strains of GBR. Subsequent immunoprecipitation reactions confirmed the presence of anti-IDIR antibodies among the U.S. population. Of 129 human serum specimens, 3 specifically immunoprecipitated the IDIR gene 8 polypeptide. PMID- 1311337 TI - Comparison of four techniques for detection of antibodies to cytomegalovirus. AB - Four serological methods were compared and evaluated for use in detecting cytomegalovirus antibody in blood and organ donors. Western blotting (immunoblotting), latex agglutination, enzyme-linked immunosorbent assay, and a recent available microparticle enzyme immunosorbent assay were used. The microparticle enzyme immunoassay appears to compare favorably with each of the other three assays tested for screening blood and organ donors for a previous cytomegalovirus infection. PMID- 1311338 TI - Development and clinical significance of a diagnostic assay based on the polymerase chain reaction for detection of human cytomegalovirus DNA in blood samples from immunocompromised patients. AB - The presence of human cytomegalovirus (HCMV) DNA in blood was investigated by the polymerase chain reaction (PCR) in 293 blood samples from 86 immunocompromised patients. Of the 86 patients, 23 underwent clinical and virologic follow-up for HCMV infection. In parallel, blood samples were examined for viremia and antigenemia. Concordant results between PCR and assays for viremia and antigenemia were obtained on 124 positive and 110 negative samples, with an overall concordance of 79.8%, while 59 samples (most from patients with HCMV infection) were positive by PCR alone. PCR is a new powerful tool for detection of HCMV infections in blood samples from immunocompromised patients. However, its clinical significance appears to be restricted to the indication of a risk of reactivation of HCMV infection. PMID- 1311339 TI - Evaluation of an enzyme-linked immunoassay employing a covalently bound capture antibody for direct detection of herpes simplex virus. AB - The FDL enzyme-linked immunosorbent assay (ELISA; Fairleigh Dickinson Laboratories, Inc., Abilene, Tex.) for the detection of herpes simplex virus (HSV) makes use of a covalently attached antibody. This assay was compared with viral isolation and with the Ortho HSV Antigen Detection ELISA (Ortho Diagnostic Systems, Inc., Raritan, N.J.). One hundred forty-eight specimens were tested. The FDL ELISA identified 66 of 104 specimens from which HSV was isolated, yielding a sensitivity of 63% and a specificity of 95%. These results compared favorably with those obtained by using the Ortho ELISA. The total test time was shorter and the washing step was simpler than that with the Ortho assay, making the FDL assay an attractive alternative to similar methodologies. PMID- 1311341 TI - The extensor carpi radialis longus muscle flap for anterior elbow coverage. AB - A muscle group resection for treatment of malignant fibrous histiocytoma of the distal arm exposed a 15 cm length of radial nerve. The soft tissue defect and radial nerve were covered with an extensor carpi radialis longus muscle island flap. The proximal dominant vascular pedicle enabled extensive mobilization and transposition of this muscle to cover the defect while preserving normal elbow, radial nerve, and hand function. Because of its ease of elevation, extensive arc of rotation, and its expendability, the extensor carpi radialis longus muscle flap should be considered as an option for reconstruction of defects about the elbow joint. PMID- 1311340 TI - Influence of animal age on the beta-adrenergic system in cultured rat aortic and mesenteric artery smooth muscle cells. AB - It has previously been reported that aortic smooth muscle cells cultured from old rats have a marked decline in beta-adrenergic stimulated cAMP accumulation. We wished to confirm this observation and determine whether this decline was secondary to loss of beta-adrenergic receptors (BAR). Primary cultures of aortic and mesenteric artery smooth muscle cells were obtained by enzymatic digestion from young and old male Fischer 344 rats. In aortic cells from old animals, there was a decline in beta-adrenergic receptor density and a rightward shift in the dose response curve to isoproterenol without a change in maximal cAMP accumulation. In mesenteric artery cells, there were no age changes in these parameters. Beta-adrenergic receptor subtype distribution was determined and was similar between all age groups and vessel types. These findings differ from whole tissue studies and suggest that cultured smooth muscle cells have limitations as a model for the aging adrenergic system. PMID- 1311343 TI - Nonadjacent syndactyly in the congenital constriction band syndrome. AB - Hand anomalies in the amniotic band sequence are frequently both complex and difficult to explain in terms of our conventional understanding of limb embryogenesis. A case manifesting pseudosyndactyly between nonadjacent fingers confirms the role of an in utero disturbance after the seventh week, in concert with close apposition between nearby but not adjacent parts. PMID- 1311342 TI - The pulp plasty: a composite graft for complete syndactyly fingertip separations. AB - Composite grafts of skin and subcutaneous fat harvested from the glabrous non weight-bearing areas of the foot were used to graft 34 fingertips after separation of 23 complete syndactyly webs in 13 patients. Simple complete syndactylies accounted for 17% and complex complete syndactylies accounted for 83%; synonychia was encountered in 70%. Follow-up averaged 13.9 months (minimum, 2 months, maximum 33 months). All patients had 100% take of the composite graft. Subjective gradings were 94% good, 6% fair, and there were no poor results. This technique provides a relatively normal contour and satisfactory pad to the fingertip. PMID- 1311344 TI - Electrodiagnosis of Martin-Gruber connection and its clinical importance in peripheral nerve surgery. AB - We propose new criteria for the electrodiagnosis of Martin-Gruber connection. Forty-seven patients with cubital tunnel syndrome were studied, and 8 (17%) were found to have a Martin-Gruber connection. Eighty-seven patients without cubital tunnel syndrome were also studied, and 14 (16%) had a Martin-Gruber connection. The rate of occurrence of the anastomosis in these two groups was approximately the same. No sensory communication was demonstrated, and the lateral intrinsic muscles received more innervation from the communicating branch than the hypothenar muscles. The entry point of the crossing fiber from the median nerve to the ulnar nerve was 3 to 10 cm distal to the medial humeral epicondyle, and there may be a significant risk of injury in ulnar nerve transposition. PMID- 1311345 TI - Sensory recovery after median nerve grafting. AB - Fourteen patients were evaluated prospectively after median nerve grafts. Twelve male and two female patients with a mean age of 41 years were included. Mean time since surgery was 4 years. Detailed sensory evaluations were completed. Statistical evaluation analyzed relationships between object identification, sensory tests, and graft length. According to the S-0 to S-4 grading system, 11 patients were considered to be S-3+ or greater. Recovery of moving two-point discrimination of 2 to 3 mm. was achieved by 50% of the patients. Strong correlations were found between object identification and static two-point discrimination, moving two-point discrimination, and graft length. Cutaneous pressure threshold and vibration threshold correlated weakly with object identification. PMID- 1311346 TI - Radial nerve rupture after a traction injury: a case report. AB - A case in which a patient sustained a closed rupture of the radial nerve at the lateral intramuscular septum from a traction injury is presented. No humeral fracture occurred, and the patient regained substantial function after delayed primary repair. PMID- 1311347 TI - Functional and biochemical characterization of a calcium-ionophore-induced state of unresponsiveness in a cytolytic T cell clone. AB - To characterize the requirements for the induction of an anergic state in immunocompetent cells we examined the effect of an increase in intracellular calcium concentration on the subsequent responsiveness of cytolytic T cells to antigenic stimulation in vitro. Pretreatment of a murine cytolytic T cell clone with the calcium-ionophore A23187 resulted in the induction of an anergic state characterized by a decrease in cytolytic activity and granule exocytosis upon Ag specific stimulation. Furthermore, IFN-gamma synthesis declined whereas de novo synthesis of a yet unidentified protein with a molecular mass of 33 kDa as well as proliferative response of cells in response to exogenous IL-2 were unaffected. This state of partial unresponsiveness 1) could be prevented by concomitant pretreatment of cells with cyclosporin A or protein synthesis inhibitors and 2) was reversible within 48 h. Biochemical analysis of TCR-induced intracellular activation revealed a block in signal transduction before the activation of protein kinase C because cellular unresponsiveness could be bypassed by the phorbol ester PMA plus the calcium-ionophore A23187. However, phosphatidylinositol turnover was markedly inhibited in unresponsive cells that also did not show a calcium influx on stimulation with concanavalin A. We conclude that a rise in intracellular calcium in cytolytic T cells might not only be necessary for cellular activation but may also trigger the induction of a partial unresponsiveness to antigenic stimulation due to an inhibition in the early phase of signal transduction. PMID- 1311348 TI - IFN-gamma induces expression of Fc gamma RIII (CD16) on human eosinophils. AB - The extent to which eosinophils constitutively express FcRIII (CD16) is controversial. We were unable to detect this receptor on freshly isolated, peripheral blood eosinophils. The capacity of eosinophils to change their Fc gamma R expression in vitro has not been previously demonstrated. Culture with IFN-gamma for 1 to 2 days induced FcRIII expression on eosinophils. This effect was dose-dependent and significant at concentrations of 100 U/ml IFN-gamma and above. Expression of FcRI (CD64) and FcRII (CDw32) was also upregulated. These increases were inhibited by cycloheximide (10(-6) M), suggesting a requirement for protein synthesis, and dexamethasone (10(-6) M). Northern blot analysis demonstrated the presence of FcRIII mRNA in eosinophils cultured with IFN-gamma for 2 days but not in unstimulated eosinophils. By contrast, culture with IL-3 caused an up-regulation of eosinophil FcRII expression but did not induce expression of FcRI or FcRIII. The FcRIII expressed by eosinophils after IFN-gamma stimulation was functionally active, as shown by the triggering of eosinophil membrane depolarization and LTC4 generation by an anti-CD16 mAb. Treatment of IFN gamma-stimulated eosinophils with phosphatidylinositol-specific phospholipase C reduced FcRIII expression, suggesting that, like neutrophils, eosinophils express the phosphatidylinositol glycan-linked form of this receptor. Therefore, this study demonstrates that IFN-gamma-treated eosinophils express a functionally active, phosphatidylinositol glycan-anchored form of FcRIII. PMID- 1311349 TI - Protective effects of soluble CR1 in complement- and neutrophil-mediated tissue injury. AB - Complement activation is an important step for triggering of acute inflammatory reactions. Soluble human recombinant complement receptor type 1 (sCR1) blocks complement activation by both classical and alternative pathways. In addition to glycogen-induced peritonitis, three models of complement-dependent acute inflammatory injury have been used to assess the protective effects of sCR1: lung and dermal injury after intraalveolar or intradermal deposition of IgG immune complexes; acute lung injury resulting from intravascular activation of complement after the i.v. injection of cobra venom factor; and acute skin and lung injury (at 4 h) after thermal trauma involving 25 to 30% total body surface area. Vascular injury was quantified by increases in vascular permeability, hemorrhage, neutrophil infiltration, and, as indicated, tissue water content. Intravenous infusion of sCR1 reduced lung and dermal vascular injury in all models studied. In glycogen-induced peritoneal exudates sCR1-reduced neutrophil accumulation by 79%. In animals undergoing IgG immune complex-induced alveolitis, sCR1 treatment reduced vascular permeability and hemorrhage by 72 and 71%, respectively, and tissue accumulation of neutrophils was reduced by 68%. After cobra venom factor injection, sCR1 reduced increases in lung vascular permeability by 67%, hemorrhage by 73%, and lung myeloperoxidase content by 55%. Four hours after thermal injury of skin, sCR1-treated animals demonstrated significant protection against lung injury; increases in vascular permeability and hemorrhage were reduced by 45 and 46%, respectively, and myeloperoxidase content was lowered by 39%. In thermal injury of the skin, sCR1 injection reduced dermal vascular permeability by 25% at 1 h (p = NS) and 44% at 4 h. Water content in skin biopsies was also decreased. There was a dose-response relationship between the amount of sCR1 infused and the extent of protection in each of the injury models. These data demonstrate that sCR1 offers significant protection against complement-dependent tissue injury in the animal models studied and that the protective effects are related to reduced neutrophil content. PMID- 1311350 TI - Transcriptional regulation of the human IgE receptor (Fc epsilon RII/CD23) by EBV. Identification of EBV-responsive regulatory elements in intron 1. AB - EBV infection of B cells induces the B cell activation Ag, CD23 (Fc epsilon RII). CD23 remains constitutively expressed at high levels in all EBV-immortalized B cells and likely plays an important role in the initiation and maintenance of immortalization by EBV. By utilizing an EBV-negative Burkitt's lymphoma line (BJAB) and EBV-positive sublines derived from it by in vitro infection, we have examined the molecular mechanisms involved in the regulation of CD23 by EBV. By nuclear runoff analysis, we have found that induction of CD23 is mediated by transcriptional activation that occurs in the presence of the transformation competent B958 virus but not in the presence of the nontransforming P3HR-1 strain of EBV. To identify EBV-responsive transcriptional regulatory elements of CD23, we have performed reporter gene assays using plasmids containing fragments of the CD23 gene derived from its 5' terminus and adjacent flanking region transfected into EBV-positive and -negative BJAB lines. We have identified a 534-bp fragment of the gene which enhances transcription from a heterologous promoter (SV40) and reporter gene (chloramphenicol acetyltransferase) only in the presence of transformation-competent strains of EBV. Deletion of 144 bp of intron 1 from the 3' end of this fragment results in loss of EBV-responsive enhancer activity. The finding of an EBV-responsive enhancer element of CD23 is supported by mobility shift assays that demonstrated the formation of specific DNA-protein complexes between nuclear protein from transforming EBV-positive cells and the 144-bp intron sequence. These studies suggest that the transcriptional activation of CD23 by transforming strains of EBV involves regulatory elements that are located within the first intron of the gene. PMID- 1311351 TI - Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala. AB - To determine the relative efficacy and toxicity of stibogluconate and ketoconazole for the treatment of cutaneous leishmaniasis, a comparative trial was conducted in which 120 Guatemalan men with parasitologically proven cutaneous leishmaniasis were randomly divided into three treatment groups: sodium stibogluconate (20 mg of antimony per kilogram per day intravenously for 20 days), ketoconazole (600 mg per day orally for 28 days), and placebo. Treatment outcome was influenced by species. Among patients infected with Leishmania braziliensis, 24 (96%) of 25 in the stibogluconate group but only 7 (30%) of 23 in the ketoconazole group responded. Among Leishmania mexicana-infected patients, only 4 (57%) of 7 in the stibogluconate group but 8 (89%) of 9 in the ketoconazole group responded. These differences emphasize the importance of speciation in the treatment of leishmaniasis. PMID- 1311352 TI - Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants. AB - In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV seronegative lung transplant recipients of organs from seropositive donors (D+/R ) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10 21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R- patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P = .023 and P = .021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients. PMID- 1311353 TI - Cell transformation by animal papillomaviruses. PMID- 1311354 TI - Contribution of single genes within the unique short region of Aujeszky's disease virus (suid herpesvirus type 1) to virulence, pathogenesis and immunogenicity. AB - Pigs (3 and 10 weeks old) were infected intranasally with Aujeszky's disease virus (ADV) mutants that functionally lacked one of the non-essential genes in the unique short region of the genome (except the gene encoding the 11K protein). Virus excretion in oropharyngeal fluid and disease symptoms were monitored. Some pigs were killed to study pathogenesis, whereas others were challenged with virulent ADV 8 weeks after the primary infection. Mutants lacking protein kinase, or glycoproteins gp63 or gI showed reduced virulence, but mutants lacking gX or the 28K protein showed normal virulence. Glycoprotein gI appears to affect the tissue tropism of ADV in pigs, presumably by facilitating the spread of the virus through the central nervous system. In this study, there was no correlation between virulence and virus multiplication in either cultured cells or in the oropharynx in vivo. All mutants induced neutralizing antibody and complete or partial protection against challenge infection. Complete protection was obtained by inoculation with the gI and gX mutants, whereas incomplete protection was obtained using gp63 and protein kinase mutants. Complete clinical and virological protection was associated with the absence of secondary antibody responses in the serum. PMID- 1311355 TI - Processing of human cytomegalovirus envelope glycoproteins in and egress of cytomegalovirus from human astrocytoma cells. AB - The synthesis of human cytomegalovirus (HCMV) envelope glycoproteins and the production of infectious HCMV in human astrocytoma and skin fibroblast (SF) cells were analysed. HCMV envelope glycoproteins synthesized in astrocytoma cells had lower Mrs than the same glycoproteins synthesized in SF cells regardless of the strain of HCMV used, showing that the differences observed were due to differences in processing by the host cell and not the strain of HCMV used. HCMV envelope glycoproteins synthesized in astrocytoma cells were found to contain less galactosamine. Moreover, when synthesized in SF cells some HCMV glycoproteins contained a protease-resistant fragment owing to the presence of a cluster of O-linked oligosaccharides on the polypeptide. This fragment was not present when these HCMV glycoproteins were synthesized in astrocytoma cells. These data suggested that HCMV glycoproteins synthesized in astrocytoma cells contain fewer O-linked oligosaccharides. In contrast, other post-translational events such as proteolytic cleavage of the HCMV gB glycoprotein and the formation of disulphide-linked complexes did occur. The virus produced in astrocytoma cells was capable of infecting SF cells, suggesting that complete O-glycosylation is not needed to produce infectious HCMV. However, astrocytoma cells were slow to release virus into the culture medium, suggesting that a fully functional Golgi network is needed for efficient egress of HCMV from the host cell. PMID- 1311356 TI - Characterization of enveloped tegument structures (L particles) produced by alphaherpesviruses: integrity of the tegument does not depend on the presence of capsid or envelope. AB - Recent studies have shown that infection with herpes simplex virus type 1 (HSV-1) strain 17 generates in addition to virions a novel type of non-infectious particle. These particles, termed L particles, lack capsids and viral DNA, and consist predominantly of tegument and envelope proteins. We show that L particle production is not restricted to one strain of HSV-1, and that pseudorabies virus and equine herpesvirus type 1 also release particles which are similar in composition to and morphologically indistinguishable from HSV-1 L particles. Data obtained from monoclonal antibody analysis revealed that Vmw175, an immediate early HSV-1 polypeptide which had been previously identified as a virion component, is located predominantly in L particles and not in virions. Following removal of the envelope from L particles, the remaining tegument material largely retained its structural integrity, indicating that the structure of the tegument does not depend on the presence of the capsid or envelope. PMID- 1311357 TI - Assembly of enveloped tegument structures (L particles) can occur independently of virion maturation in herpes simplex virus type 1-infected cells. AB - Cells infected with a number of alphaherpesviruses produce non-infectious virion related particles, termed L particles, in addition to infectious virions. L particles consist of the tegument and envelope components, but lack the virus capsid and DNA. Using a herpes simplex virus type 1 (HSV-1) temperature-sensitive mutant, ts1201, which fails to produce mature virions, we show that L particle production is independent of virion formation. Moreover, the quantity and protein composition of L particles generated by this mutant at the non-permissive temperature are indistinguishable from those produced in wild-type HSV-1 infections. Electron microscopy studies suggest that the processes governing the assembly of tegument and envelope components into L particles are similar to those involved in virion maturation. PMID- 1311358 TI - Analysis of intrastrain recombination in herpes simplex virus type 1 strain 17 and herpes simplex virus type 2 strain HG52 using restriction endonuclease sites as unselected markers and temperature-sensitive lesions as selected markers. AB - The viral and host factors involved in herpes simplex virus (HSV) recombination are little understood. To identify features of the process, recombination in HSV 1 and HSV-2 has been studied by analysing the segregation of unselected markers in the form of restriction endonuclease (RE) sites. By confining parental interactions to only one strain of virus of each serotype, restrictions imposed by non-homology are overcome and differential growth phenotypes can be discounted. The analysis of unselected and selected recombinants using RE sites in conjunction with temperature-sensitive mutations is consistent with (i) HSV being highly recombinogenic, (ii) parental and progeny molecules taking part in the process, (iii) the four genomic isomers participating in recombination, (iv) genome alignment being part of the recombination process and (v) cellular factors in conjunction with genome homology influencing the efficiency of recombination. PMID- 1311359 TI - The UL13 virion protein of herpes simplex virus type 1 is phosphorylated by a novel virus-induced protein kinase. AB - Herpes simplex virus type 1 (HSV-1) induces a protein kinase (PK) activity in infected cell nuclei. In vitro, the enzyme is able to phosphorylate exogenous casein (albeit inefficiently) but not protamine, can use ATP or GTP as a phosphate donor, is stimulated by high salt concentrations and is insensitive to inhibition by heparin. On the basis of these properties, the PK appears to be distinct from previously described cellular enzymes and from the cytoplasmic PK encoded by the viral US3 gene. A major substrate of the enzyme in vitro is a virus-induced protein with an Mr of 57000 (Vmw57). The gene encoding Vmw57 was mapped using recombinants between HSV-1 and HSV-2 to a region of the virus genome containing genes UL9 to UL15. Use of a monospecific rabbit antiserum showed that Vmw57 is a virion structural protein encoded by gene UL13. These results, in conjunction with previous reports that the UL13 protein contains PK sequence motifs, support the notions that the nuclear PK and Vmw57 are identical, and that the observed reactivity is due to autophosphorylation. PMID- 1311360 TI - Herpes simplex virus type 1 origin-dependent DNA replication in insect cells using recombinant baculoviruses. AB - The minimal set of seven herpes simplex virus type 1 (HSV-1) genes required for viral origin-dependent DNA synthesis was previously identified using a transient replication assay in a mammalian cell line permissive for HSV-1 growth. We have constructed recombinant baculoviruses which efficiently express the products of each of these seven genes in infected Spodoptera frugiperda (Sf) insect cells. When Sf cells were transfected with a plasmid containing a functional HSV-1 origin of replication, and subsequently superinfected with a mixture of these seven viruses, the input plasmid was amplified. This amplification exhibited properties characteristic of genuine HSV-1 DNA replication: all seven HSV-1 replication gene products were required, replicated DNA was detected as concatemers, and mutated origins were impaired to similar extents in insect cells and cells permissive for HSV-1 replication. These results demonstrate that the HSV-1 proteins expressed in Sf cells are fully competent for viral DNA synthesis, and indicate that any host function essential in mammalian cells must also be present in the infected insect cells. This system also provides a convenient method by which mutated replication proteins can be screened for function and produced in amounts sufficient for biochemical studies. Using this approach we show that the ability of the UL9 protein to bind to the viral origins of replication is not sufficient for it to facilitate DNA synthesis. PMID- 1311361 TI - The effect of cicloxolone sodium on the replication of vesicular stomatitis virus in BSC-1 cells. AB - The effect of cicloxolone sodium (CCX) on the replication of vesicular stomatitis virus (VSV) was investigated. The drug was active during all stages of the virus replication cycle, indicating that it does not operate by the specific inhibition of any single essential virus gene product. The drug reduced the number of VSV particles assembled and released by 100- to 1000-fold. Infectious virus yield was reduced 1000- to 10000-fold, giving a 10-fold or greater increase in the particle/p.f.u. ratio. The reduced number of virus particles produced in the presence of CCX results from two superimposed effects: suppression of VSV secondary transcription and viral protein synthesis, and perturbation of virion assembly. The inhibition of VSV assembly is due to impairment of a Golgi apparatus function related to transport of VSV glycoprotein G to the cell surface, and is characterized by accumulation of viral G and M proteins within the cell. Incubation of VSV-infected cells in the presence of two glycosylation inhibitors, tunicamycin and monensin, similarly leads to intracellular accumulation of G and M proteins, suggesting a common mechanism of action affecting VSV virion assembly. The differential effect of CCX concentration on intracellular levels of the L, N and NS proteins was analysed. CCX also possesses a virucidal effect on mature infectious VSV particles in suspension, 300 microM reducing the VSV titre about 10-fold in 24 h at 4 degrees C or 37 degrees C. The mode of antiviral activity against VSV is compared with that against herpes simplex virus. PMID- 1311362 TI - The effect of cicloxolone sodium on the replication in cultured cells of adenovirus type 5, reovirus type 3, poliovirus type 1, two bunyaviruses and Semliki Forest virus. AB - The effect of cicloxolone sodium (CCX) on the replication of typical representatives of different virus families [adenovirus type 5 (Ad-5), reovirus type 3 (Reo-3), Bunyamwera and Germiston viruses, poliovirus type 1 (Polio-1) and Semliki Forest virus (SFV)] in tissue culture was investigated. The Golgi apparatus inhibitor monensin (Mon) and CCX were shown to have analogous effects on some aspects of virus replication. Although the Mon-like effect of CCX played no role in the antiviral activity against Ad-5, Reo-3 or Polio-1, it could entirely account for the antiviral activity against the Bunyamwera and Germiston viruses, for which inhibition of glycoprotein processing was responsible for the antiviral activity. In the case of SFV, the Mon-like activity of CCX caused cytoplasmic assembly of fully infectious SFV within vacuoles and thus impaired virus release without altering total infectious virus yield. Fewer Ad-5 and Reo-3 progeny were produced in the presence of the drug. CCX had a dose-dependent biphasic effect on the particle:p.f.u. ratio of the Reo-3 yield. At low CCX concentration (less than 50 microM) the virus yield contained poor quality, non infectious virus, but at higher CCX concentration (greater than or equal to 100 microM) low quality virus could no longer be successfully assembled. We conclude that the antiviral effect can be manifested in three ways: (i) by a reduction in the virus particle yield produced; (ii) by a loss of quality (relative infectivity); (iii) by a virucidal effect of the drug. We have previously defined three CCX sensitivity classes. Mechanisms (i), (ii) and (iii) operate against viruses belonging to class CCXs-1 [herpes simplex virus (HSV) type 1, HSV-2 and vesicular stomatitis virus], but essentially only (i) and (ii) affect Reo-3 (CCXs 2), whereas (i) and possibly (iii) affect Ad-5 (CCXs-2). In the case of SFV (CCXs 3) none of these mechanisms operate, but relocation of assembled virus is found. PMID- 1311363 TI - Human papillomavirus type 6a DNA in the lung carcinoma of a patient with recurrent laryngeal papillomatosis is characterized by a partial duplication. AB - Transcriptionally active human papillomavirus type 6a (HPV-6a) DNA was detected in a lung carcinoma of a patient with recurrent laryngeal papillomatosis. The carcinoma contained episomal HPV-6a genomes that had a duplication of the upstream regulatory region, the late region and a portion of the early region. HPV-6a genomes found in benign laryngeal papillomas from the same patient did not contain this duplication. A role for the mutant molecules in the pathogenesis of the malignancy is suggested. PMID- 1311364 TI - Repression of human cytomegalovirus major immediate early gene expression in a monocytic cell line. AB - We have previously shown that a major site of persistence of human cytomegalovirus (HCMV) in healthy carriers is in peripheral blood monocytes. However, monocytes are difficult to infect in vitro with HCMV, and HCMV gene expression cannot be reproducibly detected in peripheral blood cells of healthy carriers. Here we show that the monocytic cell line THP1 is non-permissive for HCMV infection due to a block in expression of the HCMV major immediate early (IE) promoter. This repression is correlated with the presence of a differentiation-specific cellular factor which binds to the imperfect dyad symmetry and the 21 bp enhancer repeats of the major IE promoter regulatory region and which has characteristics of MBF1, a factor which we have previously defined in HCMV non-permissive, undifferentiated teratocarcinoma cells. Both differentiation of THP1 cells into macrophages, which results in a decrease in this factor, or deletion of the factor's binding sites from the IE promoter/enhancer lifts this repression and permits expression from the major IE promoter. PMID- 1311365 TI - Nuclear expression of the lower matrix protein of human cytomegalovirus in peripheral blood leukocytes of immunocompromised viraemic patients. AB - Peripheral blood leukocytes (PBL), namely polymorphonuclear leukocytes (PMNL), are the major carrier of human cytomegalovirus (HCMV) in the blood of immunocompromised patients with HCMV viraemia. By using monoclonal antibodies (MAbs) directed against different early and late viral proteins, we showed that the protein accumulating in PBL, originally reported to be an immediate early (IE) gene product, is the 65K lower matrix early structural protein (ep65). This protein is detectable by immunofluorescence before IE proteins during early stages of the replication cycle of HCMV in permissive human embryonic lung fibroblast cells. However, the appearance of ep65 in the nucleus within 1 h post infection in the presence of cycloheximide indicates that it represents uptake from the virus inoculum rather than newly synthetized protein. The ep65 MAbs staining PBL did not react with Vero cells infected with a recombinant vaccinia virus encoding the major IE gene (IE1) product, whereas MAbs reactive with the 72K major IE protein stained only faintly a small number of infected PBL. A group of four ep65 MAbs was tested in competitive binding assays to show that ep65 possesses at least three distinct epitopes. These were recognized by all four MAbs in AD169-infected Vero cell cultures when fixed with formaldehyde, whereas only one MAb recognizing a distinct epitope was reactive with methanol-acetone (MA)-fixed AD169-infected Vero cells. In formalin-fixed PBL the number of infected cells stained by the four ep65 MAbs was about twofold that found using MA-fixed cells. Using fluorescence-activated cell sorter-purified leukocyte subpopulations from viraemic patients with different levels of viraemia, the ratio of ep65-positive to ep65-negative cells was found to be 1:100 to 1:100,000 for PMNL, and only 1:10,000 to 1:100,000 for mononuclear cells. PMID- 1311366 TI - Analysis of human herpesvirus 6 glycoproteins recognized by monoclonal antibody OHV1. AB - A virus-specific glycoprotein (gp) from human herpes-virus 6 (HHV-6) was studied using the anti-HHV-6 monoclonal antibody OHV1. Immunoprecipitation with extracts from infected cells revealed that the antibody recognized four glycosylated proteins (gps) with Mrs of 106K, 102K, 65K and 63K under reducing conditions. However, only two gps, of 106K (gp106) and 102K, were detected under non-reducing conditions. Pulse-chase experiments revealed that gp65 and gp63 were cleavage products of gp106 and gp102. When infected cells were treated with tunicamycin, none of these gps was detected. With endo-beta-N-acetylglucosaminidase H (endo H) and endo-beta-N-acetylglucosaminidase F (endo F) treatment, gp106 and gp102 disappeared. Moreover, gp65 and gp63 were not affected by endo H treatment but were sensitive to endo F treatment. These data suggest that sugar residues of gp106 and gp102 are high-mannose type N-linked oligosaccharides, whereas those of gp65 and gp63 are complex type N-linked oligosaccharides. PMID- 1311367 TI - Protective immunization against Epstein-Barr virus-induced disease in cottontop tamarins using the virus envelope glycoprotein gp340 produced from a bovine papillomavirus expression vector. AB - Inoculation with Epstein-Barr virus (EBV) induces malignant lymphomas in the cottontop tamarin (Saguinus oedipus oedipus). This provides an experimental animal model for assessing the efficacy of candidate EBV vaccines which are intended to reduce the incidence of human tumours associated with EBV infection. Previous work has shown that experimental vaccines based on the major virus envelope glycoprotein gp340 prepared from the membranes of EBV-infected cells are effective in protecting cottontop tamarins against EBV-induced disease. However, not all purified gp340 preparations induce protective immunity against EBV lymphoma in the tamarin. In this work, cottontop tamarins were immunized with recombinant gp340, produced using a bovine papillomavirus (BPV) expression vector, and a threonyl muramyl dipeptide adjuvant formulation. Although the recombinant-derived gp340 lacked the membrane anchor sequence of authentic gp340 and was expressed in mouse cells, it was immunogenic and induced virus neutralizing antibodies. Healthy vaccinated tamarins were protected against EBV induced disease. The demonstration that a recombinant gp340 product is able to elicit protective immunity in the cottontop tamarin is a significant step in the development of an EBV vaccine because previously it had not been clear whether a recombinant product would have the exact tertiary structure, including the necessary carbohydrate components, to induce protective immunity. A recombinant gp340 vaccine offers various advantages over production of the authentic molecule by laborious biochemical separation, including lower cost and the absence of potentially oncogenic EBV DNA. Therefore, recombinant gp340 produced using the BPV expression vector is suitable for development as a candidate EBV vaccine for a human Phase I trial and beyond. PMID- 1311368 TI - One-step typing of Epstein-Barr virus by polymerase chain reaction: predominance of type 1 virus in Japan. AB - The prevalence of two types of Epstein-Barr virus (EBV) in Japan was studied by using the polymerase chain reaction (PCR). The U2 region encoding EBV nuclear antigen 2 (EBNA-2) was chosen as the target of amplification. Consensus primers were synthesized from sequences common to the two types but encompassing a large stretch of deletion in the sequence of type 1 EBV. The primers were capable of amplifying both types at the same time but allowed differentiation of each type by the size of the amplification products. Thus we could carry out detection and typing of EBV in a one-step PCR. EBV was detected in mouth washings of 21 (23%) of 91 seropositive healthy adults. Twenty samples (22%) contained type 1 and only one (1%) type 2. Seventy-nine patients suffering from various types of tonsillitis were also studied. EBV was detected in mouth washings of 37 patients (47%). Thirty-four (43%) contained type 1 and three (4%) type 2. Double infection was not seen in either healthy donors or patients. These results indicate that type 1 EBV is highly dominant and the type 2 variant is quite rare in Japan. PMID- 1311369 TI - Prevalence of the A and B types of Epstein-Barr virus DNA in nasopharyngeal carcinoma biopsies from southern China. AB - Epstein-Barr virus (EBV) exists in the human population in two genetic forms, usually referred to as type A and type B. Although many earlier studies had indicated that the A type was generally predominant, there were suggestions that the B type may exhibit a preferential tropism for nasopharyngeal epithelial cells. This study examines the prevalence of the two forms of EBV DNA present in nasopharyngeal carcinoma biopsies obtained from the high incidence area of Southern China. The results obtained by Southern blot or polymerase chain reaction analyses show that in this patient group the A type of EBV is predominant. PMID- 1311370 TI - Identification and characterization of the virion-induced host shutoff product of herpes simplex virus gene UL41. AB - The virion-induced host shutoff product of the herpes simplex virus UL41 gene is required for shutoff of host translation and degradation of cellular mRNAs. We employed a rabbit antipeptide antiserum to identify a 58K UL41-related phosphoprotein in infected cells. We also provide evidence that this protein is a component of the virus particle, consistent with its role in virion-induced shutoff. PMID- 1311371 TI - Characteristics of intravenous drug users by history of arrest and treatment for drug use. AB - Typically, intravenous drug users are studied by drawing samples from drug treatment programs, from the criminal justice system, or by outreach into the street community via anthropological or ethnographic methods. Among 1405 subjects recruited through extensive community outreach, 46% reported no history of treatment for drug abuse and 16% said they had not been arrested in the preceding 10 years; 130 (9%) reported neither history. A history of arrest was higher among men and those with a history of: treatment for drug abuse, low educational attainment, having received public assistance, and unemployment. A history of drug treatment was higher among women and those of an older age with a history of: arrest, having received public assistance, and a greater duration and intensity of intravenous drug use. Intravenous drug users who had neither a history of arrest since 1977 nor of drug treatment were more likely to be women and more educated, to have not received public assistance, and to inject less than weekly. These data indicate that characteristics of intravenous drug users differ by history of arrest and treatment, substantiating reports of heterogeneity among intravenous drug users. PMID- 1311373 TI - Autonomic dysfunction in diphtheritic neuropathy. AB - Sympathetic and parasympathetic function and somatic nerve conduction were assessed in ten patients with diphtheritic neuropathy and 28 controls. None of the patients had postural hypotension. The Valsalva ratio was abnormal in two patients who also had myocarditis, but it was normal in five cases. Cardiac vagal dysfunction was found in five patients. One case showed cardiac parasympathetic denervation despite normal conduction velocity in the limbs. PMID- 1311372 TI - Peripheral neuropathy in essential mixed cryoglobulinaemia. AB - The prevalence of various forms of peripheral neuropathy has not been previously assessed in large series of patients with essential mixed cryoglobulinaemia (EMC). Clinical and electrophysiological signs of peripheral neuropathy were observed in 21 of 37 EMC patients, consisting of polyneuropathy in 19, mononeuropathy or multiple mononeuropathy in eight, and both in six. The various forms of peripheral neuropathy occurred differently in the subgroups of EMC. Isolated polyneuropathy was more common with type II (eight of 10) than type III EMC (two of eight). Multifocal neuropathy, in association with polyneuropathy, was the most common form in type III EMC (five of eight). Patients with peripheral neuropathy and type II EMC were significantly older than type II EMC patients without neuropathy, regarding present age and age of onset of EMC. Patients with peripheral neuropathy and type III EMC tended to have higher values of ESR and IgM than type III EMC patients without neuropathy. Electrophysiological findings and sural nerve biopsy specimens (nine cases) showed prominent axonal changes. Vascular changes included vasculitis and alterations of the endoneurial microvessels in type II and type III EMC. Our findings suggest that distinct pathogenic factors are implicated in the subgroups of cryoglobulinaemic neuropathy, possibly inducing different types of vascular changes underlying polyneuropathy or, respectively, mononeuropathy and multiple mononeuropathy. PMID- 1311374 TI - Immunohistochemical demonstration of the Epstein-Barr virus-encoded latent membrane protein in paraffin sections of Hodgkin's disease. AB - Paraffin sections from 46 cases of Hodgkin's disease were examined for the presence of the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) using a sensitive (double layer alkaline phosphatase-anti-alkaline phosphatase) immunohistochemical method. LMP was detected in 22 cases, the majority of positive cases being of nodular sclerosis (12/24), mixed cellularity (6/7), and lymphocyte depletion (3/3) subtypes. Only one of 12 cases of lymphocyte predominant disease was positive. In all cases, reactivity was confined to Hodgkin's and Reed-Sternberg cells. These results provide further evidence for an association between EBV and Hodgkin's disease and indicate that LMP may be readily detected in archival material. PMID- 1311375 TI - alpha B crystallin expression in non-lenticular tissues and selective presence in ubiquitinated inclusion bodies in human disease. AB - alpha B crystallin is a lens protein which has homology with the small heat-shock proteins and is also expressed in non-lenticular tissues. Polyclonal antibodies have been raised to a synthetic peptide corresponding to residues 1-10 of alpha B crystallin. The antiserum detects a 20 kDa polypeptide on nitrocellulose replicas after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate of extracts of heart muscle known to be rich in alpha B crystallin. Staining of normal human tissues reveals immunoreactivity of lens capsular epithelium, skeletal muscle, cardiac muscle, smooth muscle, renal tubular epithelium, Schwann cells, and glial cells, as has been described by other workers. In addition, positive staining of normal thyroid epithelium, colonic epithelium, and stratified squamous epithelium was seen. Tissues known to contain ubiquitinated inclusion bodies were immunostained with the anti-alpha B crystallin antiserum. Staining of cortical Lewy bodies, astrocytic Rosenthal fibres, and hepatic Mallory bodies was seen, but only a proportion of inclusions were positive. Neurones containing the ubiquitinated inclusions of Alzheimer's disease were only very rarely immunostained and the ubiquitinated inclusions of motor neurone disease were not detected by the antiserum. Reactive astrocytes in cerebral tissues were strongly immunostained. The results suggest that alpha B crystallin is involved in the formation of ubiquitinated inclusion bodies that have associated intermediate filaments and support previous observations on the localization of a brain-specific ubiquitin carboxy-terminal hydrolase which similarly divides ubiquitinated filamentous inclusions in the central nervous system into two main groups. PMID- 1311376 TI - Evaluation of renal scars by technetium-labeled dimercaptosuccinic acid scan, intravenous urography, and ultrasonography: a comparative study. AB - The objective of our prospective study was to compare the sensitivity and specificity of ultrasonography, intravenous pyelography, and dimercaptosuccinic acid scan in detecting scarred kidneys. Twenty-seven consecutive subjects with recurrent urinary tract infections, vesicoureteral reflux, scarred kidneys, or a combination of these problems had all three imaging procedures performed. With the total number of scars serving as the gold standard, the sensitivity (94%) and specificity (100%) in identifying renal scars in children were highest for the DMSA scan. Intraobserver (95%) and interobserver (90%) reliability were also high for the DMSA scan. However, the clinical interpretation of the increased sensitivity of the DMSA scan is unknown. Changes on the scan not identified by intravenous urography may not represent true scars. Research into the long-term significance of these scars is indicated. PMID- 1311377 TI - Mother-to-infant transmission of hepatitis C virus. AB - Prospective studies of an infant of a mother infected with hepatitis C virus indicated that an HCV infection developed in the infant in early life. Perinatal transmission appeared to be the most likely explanation. PMID- 1311378 TI - Treatment of aggressive cytomegalovirus retinitis with ganciclovir in combination with foscarnet in a child infected with human immunodeficiency virus. AB - Ganciclovir and foscarnet are both effective for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome, but the benefits of either agent given alone are limited. A child infected with human immunodeficiency virus who had cytomegalovirus retinitis that progressed despite treatment with either agent alone received the combination of ganciclovir and foscarnet. This treatment resulted in a sustained clinical response. PMID- 1311379 TI - Microleakage between different types of base materials. AB - This study investigated the sealing properties of various combinations of base materials. Three chemically cured and three light-activated base materials were combinationally used to make 15 sample groups. The samples were thermocycled and immersed in 0.05% crystal violet solution for 1 hour. They were then embedded in clear casting resin, sectioned, and photographed. The interfaces of the samples were digitized. The ratio of the total interface length to the penetration of leakage was calculated and compared. The results indicated that the combination of Cavalite and VLC Dycal materials had the least microleakage and was significantly different from the other 14 groups. PMID- 1311380 TI - Identifying human papillomavirus subtypes in cervical biopsies with in situ DNA hybridization with biotinylated probes. AB - To test the utility of biotinylated DNA probes against various subtypes of human papillomavirus (HPV), we performed in situ DNA hybridization on routinely processed archival material from 30 patients with serial cervical biopsies including conization (group I) and a prospective group of 35 patients whose cervical biopsies showed various degrees of koilocytotic atypia and/or dysplasia (group II). Commercially available biotinylated probe cocktails against HPV types 6 and 11, 16 and 18, and 31, 35 and 51 were detected via the avidin-biotin horseradish peroxidase technique. Virus was found in 87% (26/30) of group I and 57% (20/35) of group II. Almost exclusively, viral types 16, 18, 31, 35 and 51 were detected in group I; 54% (19/35) of group II stained for types 16, 18 or 31, 35 and 51; 2.9% (1/35) stained for types 6 and 11. Nine percent of group II (3/35) showed coinfection with types 16, 18 and 31, 35 and 51. Three of six vulvar condylomata (50%) stained for types 6 and 11. In general, weaker staining was associated with greater dysplasia. In situ hybridization using biotinylated DNA probes is useful in identifying patients infected with dysplasia/carcinoma associated HPV subtypes and can be performed easily on routine surgical specimens. PMID- 1311381 TI - Human papillomavirus in women. A three-year experience in a county hospital colposcopy clinic. AB - The human papillomavirus (HPV) has been associated with cervical dysplasia and carcinoma. This report summarizes the authors' experience with HPV-related problems over three years, 1987-89, while managing 1,644 women at a county hospital colposcopy clinic. Probes for HPV DNA were not used, and the diagnoses were made with cytologic and histologic criteria alone. The percentage of patients referred to the clinic with HPV found on routine Papanicolaou smears rose significantly, from 3 in 1987 to 18 in 1989. Fifteen percent of those referred because of HPV on a Papanicolaou smear were found to have cervical intraepithelial neoplasia (CIN) grade II or III after they were evaluated at the clinic. Of the 367 cases of biopsy-proven cervical HPV, only 33 (9%) were recorded on Papanicolaou smears performed immediately before the biopsy, and 140 (38%) also had concomitant, biopsy-proven CIN, grade II or III. Of the 195 instances in which the colposcopic impression was simple HPV without CIN, 46 (24%) had high-grade CIN on biopsy. We conclude that the proportion of patients with HPV-associated problems is increasing, that the Papanicolaou smear is not sensitive in detecting cervical HPV infections, that patients with HPV changes found on Papanicolaou smears should be evaluated with colposcopy and that lesions that appear colposcopically to be simple HPV should undergo biopsy to rule out the presence of high-grade CIN. PMID- 1311383 TI - Familial adenomatous polyposis. PMID- 1311382 TI - Meeting report. Report of meeting of Section of Clinical Immunology and Allergy, 11 March 1991. PMID- 1311384 TI - Rectal polyposis as a guide to duodenal polyposis in familial adenomatous polyposis. AB - Almost all patients with familial adenomatous polyposis (FAP) develop duodenal polyps, the severity of which is graded stage 1 (minor) to stage V (cancer). Regular endoscopy is recommended for all patients with FAP. To test whether the development of severe duodenal polyposis could be predicted in another way, rectal and duodenal polyp severity were compared in 91 patients with FAP. The fulguration ratio (number of rectal fulgurations divided by number of years since colectomy) supplied the rectal polyp severity index. Patients with stage V duodenal polyposis had significantly higher fulguration ratios (median 0.38) than did patients with stage 1 disease (median 0; P = 0.009). However, the wide scatter of results means that rectal polyp severity cannot be used as a guide to duodenal polyp severity in individual patients. The coexistence of populations with severe duodenal and rectal polyposis suggests that environmental factors are important in phenotypic expression in FAP. PMID- 1311385 TI - Three-dimensional structure of a mutant ribonuclease T1 (Y45W) complexed with non cognizable ribonucleotide, 2'AMP, and its comparison with a specific complex with 2'GMP. AB - The crystal structure of a mutant ribonuclease T1 (Y45W) complexed with a non cognizable ribonucleotide, 2'AMP, has been determined and refined to an R-factor of 0.159 using X-ray diffraction data at 1.7 A resolution. A specific complex of the enzyme with 2'GMP was also determined and refined to an R-factor of 0.173 at 1.9 A resolution. The adenine base of 2'AMP was found at a base-binding site that is far apart from the guanine recognition site, where the guanine base of 2'GMP binds. The binding of the adenine base is mediated by a single hydrogen bond and stacking interaction of the base with the imidazole ring of His92. The mode of stacking of the adenine base with His92 is similar to the stacking of the guanine base observed in complexes of ribonuclease T1 with guanylyl-2',5'-guanosine, reported by Koepke et al., and two guanosine bases, reported by Lenz et al., and in the complex of barnase with d(GpC), reported by Baudet & Janin. These observations suggest that the site is non-specific for base binding. The phosphate group of 2'AMP is tightly locked at the catalytic site with seven hydrogen bonds to the enzyme in a similar manner to that of 2'GMP. In addition, two hydrogen bonds are formed between the sugar moiety of 2'AMP and the enzyme. The 2'AMP molecule adopts the anti conformation of the glycosidic bond and C-3' exo sugar pucker, whereas 2'GMP is in the syn conformation with C-3'-endo-C'-2' exo pucker. The mutation enhances the binding of 2'GMP with conformational changes of the sugar ring and displacement of the phosphate group towards the interior of the catalytic site from the corresponding position in the wild-type enzyme complex. Comparison of two crystal structures obtained provides a solution to the problem that non-cognizable nucleotides exhibit unexpectedly strong binding to the enzyme, compared with high specificity in nucleolytic activity. The results indicate that the discrimination of the guanine base from the other nucleotide bases at the guanine recognition site is more effective than that estimated from nucleotide-binding experiments so far. PMID- 1311386 TI - Structural details of ribonuclease H from Escherichia coli as refined to an atomic resolution. AB - The crystal structure of RNase H from Escherichia coli has been determined by the multiple isomorphous replacement method, and refined by the stereochemically restrained least-squares procedure to a crystallographic R-factor of 0.196 at 1.48 A resolution. In the final structure, the root-mean-square (r.m.s.) deviation for bond lengths is 0.017 A, and for angle distances 0.036 A. The structure is composed of a five-stranded beta-sheet and five alpha-helices, and reveals the details of hydrogen bonding, electrostatic and hydrophobic interactions between intra- and intermolecular residues. The refined structure allows an explanation of the particular interactions between the basic protrusion, consisting of helix alpha III and the following loop, and the remaining major domain. The beta-sheet, alpha II, alpha III and alpha IV form a central hydrophobic cleft that contains all six tryptophan residues, and presumably serves to fix the orientation of the basic protrusion. Two parallel adjacent helices, alpha I and alpha IV, are associated with a few triads of hydrophobic interactions, including many leucine residues, that are similar to the repeated leucine motif. The well-defined electron density map allows detailed discussion of amino acid residues likely to be involved in binding a DNA/RNA hybrid, and construction of a putative model of the enzyme complexed with a DNA/RNA hybrid oligomer. In this model, a protein region, from the Mg(2+)-binding site to the basic protrusion, covers roughly two turns of a DNA/RNA hybrid double helix. A segment (11-23) containing six glycine residues forms a long loop between the beta A and beta B strands. This loop, which protrudes into the solvent region, lies on the interface between the enzyme and a DNA/RNA hybrid in the model of the complex. The mean temperature factors of main-chain atoms show remarkably high values in helix alpha III that constitutes the basic protrusion, suggesting some correlation between its flexibility and the nucleic acid binding function. The Mg(2+)-binding site, surrounded by four invariant acidic residues, can now be described more precisely in conjunction with the catalytic activity. The arrangement of molecules within the crystal appears to be dominated by the cancelling out of a remarkably biased charge distribution on the molecular surface, which is derived in particular from the separation between the acidic Mg(2+)-binding site and the basic protrusion. PMID- 1311387 TI - Thermodynamic characterization of cytochrome c at low pH. Observation of the molten globule state and of the cold denaturation process. AB - Several reports have pointed out the existence of intermediate states (both kinetic and equilibrium intermediate) between the native and the denatured states. The molten globule state, a compact intermediate state in which the secondary structure is formed but the tertiary structure fluctuates considerably, is currently being studied intensively because of its possible implication in the folding process of several proteins. We have examined the thermal stability of horse cytochrome c at low pH between 2.0 and 3.2 and different potassium chloride concentrations by absorbance of the Soret band, far and near-ultraviolet circular dichroism (u.v. c.d.) and tryptophan fluorescence using a multidimensional spectrophotometer. The concentration of potassium chloride ranged from 0 M to 0.5 M. The experimental thermal denaturation curves show that: (1) the helical content of cytochrome c remains stable at higher temperature when the concentration of salt is increased; whereas (2) the extent of ordering of the tertiary structure is weakly dependent on salt concentration; and (3) for cytochrome c, the stabilization of the molten globule state is induced by the binding of anions. Other salts such as NaCl, LiCl, potassium ferricyanide (K3Fe(CN)6) and Na2SO4 may also be used to stabilize the molten globule state. The thermodynamic analysis of the denaturation curves of c.d. at 222 nm and c.d. at 282 nm shows that, whereas a two-state (native and denatured) transition is observed at low-salt concentration, the far and near-u.v. c.d. melting curves of cytochrome c do not coincide with each other at high-salt concentration, and a minimum of three different thermodynamic states (IIb, intermediate or IIc, and denatured) is necessary to achieve a sufficient analysis. The intermediate state (called IIc) is attributed to the molten globule state because of its high secondary structure content and the absence of tertiary structure. Therefore, at low pH, cytochrome c is present in at least four states (native, IIb, IIc and denatured) depending on the salt concentration and temperature. The thermodynamic parameters, i.e. the Gibbs free energy differences (delta G), the enthalpy differences (delta H), the midpoint temperatures (Tm) of the transition (IIb in equilibrium intermediate (IIc in equilibrium denatured) are determined. We also give estimates of the heat capacity differences (delta Cp) from the temperature dependence of the enthalpy differences. The enthalpy change and the heat capacity difference of the IIc in equilibrium denatured transition are non-zero. The number of charges (protons or chloride anions) released upon transitions are determined by analysing the pH and chloride anion concentration dependence of the Gibbs free energy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311388 TI - Crystallization and preliminary X-ray diffraction studies of coxsackievirus B1. AB - Preparations of coxsackievirus B1 (CVB1) derived from an infectious cDNA clone have been crystallized in multiple crystal forms. Using high intensity synchrotron radiation, an orthorhombic form of the crystals was shown to diffract X-rays to at least 2.9 A resolution. The unit cell has a primitive lattice with dimensions a = 323 A, b = 450 A, and c = 522 A. A crystallographic asymmetric unit of these CVB1 crystals probably contains an entire virus particle, implying the presence of 60-fold non-crystallographic redundancy. This CVB1 crystal form appears to be suitable for high-resolution structure determination by X-ray crystallography. PMID- 1311389 TI - Crystallization and preliminary X-ray investigation of a ubiquitin carrier protein (E2) from Arabidopsis thaliana. AB - Crystals of a recombinant ubiquitin carrier protein from Arabidopsis thaliana have been grown from solutions of ammonium sulfate. The crystals are orthorhombic, space group P2(1)2(1)2(1); the axes are a = 41.8(1) A, b = 44.9(1) A and c = 83.2(1) A. The crystals are quite stable to X-rays and diffract beyond 2.1 A resolution. There is one molecule in the asymmetric unit. PMID- 1311390 TI - Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II. AB - Cloning and sequencing of cDNA segments of human TOP2 gene encoding the 170 kDa form of human DNA topoisomerase II show that Arg486 of the enzyme has been mutated to a lysine in the enzyme from two human leukemia cell lines HL-60/AMSA and KBM-3/AMSA, which were independently selected for resistance to the antitumor drug amsacrine (4'-[9-acridinylamino]-methanesulfon-m-anisidide, mAMSA). Sequence identity comparisons between eukaryotic DNA topoisomerase II and bacterial gyrase (bacterial DNA topoisomerase II) indicate that the position of the common mutation observed in mAMSA-resistant human TOP2 corresponds to that of the point mutation nal-31 in the Escherichia coli gyrase B gene, which confers resistance to nalidixic acid. Because mAMSA and nalidixic acid are known to act on their respective targets by a common mechanism of trapping the covalent enzyme-DNA intermediates, these results provide strong evidence that the 170 kDa form of human DNA topoisomerase II is a major cellular target of mAMSA, and that Arg486 of this enzyme is involved in mAMSA-mediated trapping of the covalent enzyme-DNA complex. PMID- 1311391 TI - Oxidation state-dependent conformational changes in cytochrome c. AB - High-resolution three-dimensional structural analyses of yeast iso-1-cytochrome c have now been completed in both oxidation states using isomorphous crystalline material and similar structure determination methodologies. This approach has allowed a comprehensive comparison to be made between these structures and the elucidation of the subtle conformational changes occurring between oxidation states. The structure solution of reduced yeast iso-1-cytochrome c has been published and the determination of the oxidized protein and a comparison of these structures are reported herein. Our data show that oxidation state-dependent changes are expressed for the most part in terms of adjustments to heme structure, movement of internally bound water molecules and segmental thermal parameter changes along the polypeptide chain, rather than as explicit polypeptide chain positional shifts, which are found to be minimal. This result is emphasized by the retention of all main-chain to main-chain hydrogen bond interactions in both oxidation states. Observed thermal factor changes primarily affect four segments of polypeptide chain. Residues 37-39 show less mobility in the oxidized state, with Arg38 and its side-chain being most affected. In contrast, residues 47-59, 65-72 and 81-85 have significantly higher thermal factors, with maximal increases being observed for Asn52, Tyr67 and Phe82. The side-chains of two of these residues are hydrogen bonded to the internally bound water molecule, Wat166, which shows a large 1.7 A displacement towards the positively charged heme iron atom in the oxidized protein. Further analyses suggest that Wat166 is a major factor in stabilizing both oxidation states of the heme through differential orientation of dipole moment, shift in distance to the heme iron atom and alterations in the surrounding hydrogen bonding network. It also seems likely that Wat166 movement leads to the disruption of the hydrogen bond from the side-chain of Tyr67 to the Met80 heme ligand, thereby further stabilizing the positively charged heme iron atom in oxidized cytochrome c. In total, there appear to be three regions about which oxidation state-dependent structural changes are focussed. These include the pyrrole ring A propionate group, Wat166 and the Met80 heme ligand. All three of these foci are linked together by a network of intermediary interactions and are localized to the Met80 ligand side of the heme group. Associated with each is a corresponding nearby segment of polypeptide chain having a substantially higher mobility in the oxidized protein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311392 TI - Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. PMID- 1311393 TI - Melanotic neuroectodermal tumor of infancy: an important mimicker of paratesticular rhabdomyosarcoma. AB - We report a case of a paratesticular tumor in a 6-month-old infant. This tumor was originally believed to represent a poorly differentiated sarcoma of the cord but upon further pathological consultation it was recognized as a rare melanotic neuroectodermal tumor of infancy involving the epididymis. Since the former is a highly aggressive lesion and the latter an indolent tumor, treatment of these 2 entities differs markedly. Therefore, although the histological distinction between these lesions is often difficult, it is of critical importance. PMID- 1311394 TI - Adenoid cystic carcinoma of Cowper's gland. AB - We report an additional case of primary adenoid cystic carcinoma of Cowper's gland in an otherwise healthy asymptomatic 66-year-old man. Based on a review of similar lesions presenting in the head and neck, our treatment plan entailed pelvic exenteration followed by radiation therapy. Whether adenoid cystic carcinoma of Cowper's gland behaves as aggressively as it does in the head and neck remains unclear. However, in view of the extensive local invasion in our patient and a previously successful outcome, a combined surgical and radiation approach appears to be the most appropriate therapy. PMID- 1311395 TI - Small cell anaplastic carcinoma of the prostate: a clinical, pathological and immunohistological study of 27 patients. AB - Because small cell anaplastic carcinoma of the prostate is an uncommon tumor, it has remained a poorly defined entity. To elucidate further the clinical, pathological and immunohistochemical characteristics of this cancer the 27 patients who presented to the Mayo Clinic from 1960 to 1990 were reviewed. Of these patients 18 (67%) presented with pure small cell anaplastic carcinoma, and 9 (33%) were diagnosed with small cell anaplastic carcinoma and adenocarcinoma of the prostate. Twenty-six patients (96%) had either stage C or D disease at the time of diagnosis. Two patients presented with a paraneoplastic syndrome, including 1 man with inappropriate antidiuretic hormone secretion and 1 who suffered from thyroxine intoxication. Of 24 men with long-term followup 22 (92%) died of small cell anaplastic carcinoma of the prostate despite antiandrogen therapy and the remaining 2 are alive with active, progressive disease. The median survival time following diagnosis was 17.1 months (range 2 to 90 months). All tumors with tissue available for immunohistochemical staining reacted positive for neuron-specific enolase, indicating that small cell anaplastic carcinoma of the prostate is most likely a neuroendocrine neoplasm. No tumor stained positive for either prostatic acid phosphatase or prostate specific antigen. Pathologically, small cell anaplastic carcinoma of the prostate appears to be similar to oat cell carcinoma of the lung. This series of 27 patients emphasizes that small cell anaplastic carcinoma of the prostate is highly malignant, is frequently of advanced stage at presentation, responds poorly to antiandrogen therapy and has a poor prognosis. PMID- 1311396 TI - Chemotherapy for small cell carcinoma of prostatic origin. AB - A total of 21 patients with metastatic small cell carcinoma of the prostate was treated with combination chemotherapy, either following initial hormonal therapy (15) or as initial therapy (6). Of the patients 13 (62%) had pure small cell carcinoma, whereas 8 (38%) had mixed histology of small cell carcinoma and adenocarcinoma. Patients presented with a characteristic clinical picture of a large primary mass (16 cases) with a high frequency of visceral metastases to the liver (9), lungs (7) and brain (2). The majority of the patients did not have an elevated serum prostate specific antigen (1 of 14, 7%) or prostatic acid phosphatase (2 of 21, 10%). Serum carcinoembryonic antigen was elevated in 13 patients (62%). Of the 21 patients 13 (62%) responded to chemotherapy. Survival after the diagnosis of small cell carcinoma of the prostate resulted in a median of 9.4 months with a range of 1 to 25 months. The regimens used were those considered active in the treatment of small cell carcinoma of the lung (vincristine, doxorubicin and cyclophosphamide, or etoposide and cisplatin with or without doxorubicin). Small cell carcinoma of the prostate has a characteristic clinical picture and a high response rate to cytotoxic therapy. Early introduction of chemotherapy in the treatment of small cell carcinoma of the prostate may increase the survival rate. PMID- 1311397 TI - Development of spongiform encephalopathy in retroviral infected mice. AB - The Cas-Br-E strain of murine leukemia virus is a neurovirulent retrovirus that induces progressive noninflammatory degeneration of the central nervous system (CNS). The molecular clone pNE-8 retains pathogenic properties of Cas-Br-E. The neurotropic determinants are known; however, the mechanism of neuropathogenesis is unknown. We examined the temporal development of disease after infection of SWR/J mice with pNE-8 virus. Development of CNS lesions, cellular targets of viral replication, accumulation of ubiquitinated proteins and integrity of blood brain barrier were determined in mice infected with pNE-8 virus; and compared with uninfected, sham-infected, and nonneuropathogenic virus-infected mice. During 24 weeks of pNE-8 infection, noninflammatory spongiform lesions developed initially in the lumbar spinal cord and progressed to involve the brainstem and deep cerebellar nuclei. Virions and viral antigens accumulated for 18 weeks postinfection and then declined. Major sites of viral infection outside the CNS were splenic megakaryocytes, and skeletal muscle. Cellular targets of viral replication in the CNS included neurons, oligodendrocytes, and capillary endothelium. No astrocytic infection was observed; however, a reactive gliosis marked the development of clinical symptoms and histopathology. Spongiform lesions began as swelling of perivascular astrocytic processes. Intramyelinic vacuoles with splitting of myelin at major dense lines were prominent around dystrophic axons at later time points. Dendritic processes showed vacuolization and local degeneration. Viral particles were most commonly observed in extracellular spaces and within rough endoplasmic reticulum of neurons, oligodendrocytes, and splenic megakaryocytes. Infected megakaryocytes and regions of spleen containing viral aggregates showed accumulation of ubiquitinated proteins. Areas of histopathology in the CNS showed accumulation of ubiquitinated proteins but unlike spleen, viral proteins were not highly ubiquitinated. Disruption of the blood brain barrier was only evident at late stages of infection. In conclusion, the neuropathogenic damage associated with pNE-8 infection appears to be tightly associated with direct viral infection of oligodendroglia and neurons. PMID- 1311400 TI - [A magnet on the chest as a guide to medication]. PMID- 1311399 TI - Ductal carcinoma in situ in rat mammary gland. AB - Antiestrogen therapy has been proposed as a treatment option for ductal carcinoma in situ (DCIS). However, its effectiveness has not been evaluated in the laboratory due to lack of an animal model. The present study was undertaken to evaluate the incidence, time span, and number of mammary glands involved with DCIS in a rat model treated with N-nitroso-N-methylurea (NMU). Sprague Dawley female rats 44 to 49 days old were treated with two iv doses of 5 mg NMU/100 g body wt given 7 days apart, initiated at diestrus. Animals were killed at intervals beginning 21 days following first injection. Breast tissues were evaluated following routine H&E stain. Standard histologic criteria were followed to establish the diagnosis of DCIS. The number of glands involved with DCIS increased from one to seven with time from first injection. This model demonstrates an incidence of 87% for DCIS and 0% for invasive Ca between 22 and 45 days following NMU injection. Nine rats were sacrificed between 50 to 60 days and five showed invasive carcinoma. This model appears suitable for studying the efficacy of hormone or chemoprevention in the progression of DCIS to invasive Ca. PMID- 1311398 TI - Expression of surfactant associated protein-A and Clara cell 10 kilodalton mRNA in neoplastic and non-neoplastic human lung tissue as detected by in situ hybridization. AB - Two markers for the progenitor cells of peripheral airways and their tumors are the 10 kilodalton (kd) Clara cell protein and the major surfactant associated protein-A (SP-A). We used the RNA-RNA in situ hybridization technique to study expression of the genes encoding these proteins at the cellular level in 19 pairs of non-neoplastic and neoplastic tissues from resected human lungs. Our results show that in non-neoplastic lung tissue, the Clara 10 kd protein gene was expressed in nonciliated cells of both bronchial and bronchiolar epithelium, indicating that, in contrast to previous assumptions, cells with Clara cell-like differentiation in humans may not be restricted to bronchiolar cells. The incidence of Clara 10 kd protein gene expression, as detected in lung carcinomas (1 out of 19 cases positive) was less than expected based on previous ultrastructural reports. The SP-A gene was strongly expressed in normal alveolar type II cells in non-neoplastic lung and, at higher levels, in hyperplastic cells. In addition, SP-A mRNA expression was observed in scattered bronchial and bronchiolar epithelial cells in 40% of the airways examined. Five out of 17 lung tumors, all of which were adenocarcinomas, were positive for SP-A expression, albeit generally less intense than type II cells. This expression was seen in carcinomas with papillolepidic as well as solid and glandular growth patterns. Our findings provide new insights into the peripheral airway cell differentiation. PMID- 1311401 TI - The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. AB - The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax1) was lower in obesity than in AN or control. The low-affinity constants (Ka2) were similar in the three groups, and its binding capacity (Bmax2) was similar in the AN patients and the controls, but significantly lower in the obese. [125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311402 TI - Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects. AB - To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin releasing hormone (hCRH, 1 microgram/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d-FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 microgram/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 +/- 11.2 ng/mL v 104.1 +/- 9.5 ng/mL). This response was lower (P less than .005) than in the controls, in whom the basal cortisol value of 120.6 +/- 11.8 ng/mL reached a peak value of 221.2 +/- 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P less than .0001) plasma cortisol (peak value 170.6 +/- 18.0 ng/mL v 111.5 +/- 10.8 ng/mL) and the response was enhanced (P less than .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 +/- 1.7 pg/mL v 9.6 +/- 1.1 pg/mL), but the hormonal response was lower (P less than .005) than in controls (peak value 38.1 +/- 5.5 pg/mL v 13.8 +/- 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P less than .05) in plasma ACTH at 30 minutes (20.4 +/- 3.7 pg/mL v 10.9 +/- 0.9 pg/mL) and 45 minutes (18.0 +/- 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311403 TI - Na+/K(+)-ATPase activity and its alpha II subunit gene expression in rat skeletal muscle: influence of diabetes, fasting, and refeeding. AB - We have examined the effects of diabetes, fasting, and refeeding on Na+/K(+) adenosine triphosphatase (ATPase) activity and its catalytic alpha II subunit gene expression in skeletal muscle. Two hypoinsulinemic states, streptozotocin induced diabetes and 48-hour fasting caused a significant decrease (P less than .05) in skeletal muscle Na+/K(+)-ATPase activity and a marked increase (P less than .01) in the levels of alpha II subunit mRNA. A decrease in enzyme activity was observed on the 2nd and the 14th day of diabetes, whereas an increase in alpha II mRNA levels was found only on the 14th day. The levels of alpha I mRNA were not affected, while the levels of mRNA of the structural beta subunit were decreased on the 14th day of diabetes. Correction of hyperglycemia with insulin restored enzyme activity and alpha II isoform mRNA levels toward normal in diabetic animals. Refeeding for 48 or 72 hours restored these parameters to normal in skeletal muscle of previously fasting rats. These observations suggest that a decrease in muscle Na+/K(+)-ATPase activity may lead to a compensatory increase in its alpha II subunit gene expression. The levels of insulin and not of glycemia appear to be critical in modulating Na+/K(+)-ATPase activity and gene expression. PMID- 1311404 TI - The structure of an integrated copy of the giant linear plasmid SCP1 in the chromosome of Streptomyces coelicolor 2612. AB - In NF strain 2612 of Streptomyces coelicolor, a giant linear plasmid SCP1 is integrated into the chromosome at the 9 o'clock position. To characterize the integrated structure of SCP1, cloning and sequence analysis of the two junctions between the SCP1 DNA and the chromosomal DNA was carried out. The left junction was revealed to retain an almost intact left terminus of SCP1. On the other hand, the right junction was composed of IS466, deleting completely the right terminal inverted repeat of SCP1. This junction might have been formed by recombination of two IS466 elements, one present at the end of the right terminal inverted repeat of SCP1 and one on the chromosome. Based on these results, we have proposed a model for the integration of SCP1 into the chromosome. The unique conjugal transfer of NF strains and the origin of the chromosomal antibiotic biosynthetic genes in Streptomyces species are also discussed in relation to this model. PMID- 1311405 TI - Transactivation of Ds by Ac-transposase gene fusions in tobacco. AB - To study regulation of the (Ds) transposition process in heterologous plant species, the transposase gene of Ac was fused to several promoters that are active late during plant development. These promoters are the flower-specific chalcone synthase A promoter (CHS A), the anther-specific chalcone isomerase B promoter CHI B and the pollen-specific chalcone isomerase A2 promoter CHI A2. The modified transposase genes were introduced into a tobacco tester plant. This plant contains Ds stably inserted within the leader sequence of the hygromycin resistance (HPT II) gene. As confirmed with positive control elements, excision of Ds leads to the restoration of a functional HPT II gene and to a hygromycin resistant phenotype. No hygromycin resistance was observed in negative control experiments with Ac derivatives lacking 5' regulatory sequences. Although transactivation of Ds was observed after the introduction of transposase gene fusions in calli, excision in regenerated plants was observed only for the CHS A- or CHI B-transposase gene fusions. With these modified transposase genes, somatic excision frequencies were increased (68%) and decreased (22%), respectively, compared to the situation with the Ac element itself (38%). The shifts in transactivation frequencies were not associated with significant differences in the frequencies of germinally transmitted excision events (approximately 5%). The relative somatic stability of Ds insertions bearing the CHI B-transposase gene fusion suggests the usefulness of this activator element for transposon tagging experiments. PMID- 1311406 TI - Topoisomerase II-mediated DNA cleavage activity and irreversibility of cleavable complex formation induced by DNA intercalator with alkylating capability. AB - A group of chrysophanol and emodin derivatives with DNA-intercalating capability and with or without alkylating potential have been synthesized and shown to have antitumor activity in vitro. The topoisomerase II (Topo II)-mediated DNA cleavage activities induced by representative compounds 3-(2-chloroethylamino) methyl-1,8 dihydroxy-9,10-anthraquinone (SK-31690), 3-bis [(2-chloroethyl)amino]methyl-1,8 dihydroxy-9,10-anthraquinone (SK-31662), and 3-(2-hydroxyethylamino)methy-1,8 dihydroxy-9,10-anthraquinon e (SK-31694), and their cytotoxicities, have been investigated. All three compounds inhibited the kinetoplast DNA decatenation catalyzed by DNA Topo II. These compounds inhibited leukemia cell growth and stimulated, in a dose-dependent manner from 0.5 to 60 microM, the formation of Topo II-DNA cleavable complexes, when 3'-32P-labeled DNA was used. The mapping of Topo II-mediated DNA cleavage sites using HindIII-digested 3'-32P-labeled DNA showed that, at 10 microM, these compounds induced protein-linked DNA breaks that correlated with cytotoxicity, with respect to their maximal efficacy or the reciprocal concentration for the half-maximal effect. The reversibility study showed that the amounts of protein-linked DNA cleavage induced by 4'-(9 acridinylamino)methanesulfon-m-anisidide and VP-16 as well as SK-31694, which lacks alkylating potential, were markedly decreased during 30-sec exposure to 65 degrees or 0.5 M NaCl. In contrast, protein-linked DNA cleavages induced by SK 31662, which has two alkylating functionalities, and by SK-31690, which has one alkylating functionality in its structure, cannot be reversed during the 15-min exposure to 65 degrees or 0.5 M NaCl. These data suggest that Topo II is a major cellular target for cytotoxicity of these compounds. Furthermore, DNA intercalators with alkylating potential interact with Topo II-DNA cleavable complexes in an irreversible manner, with enhanced toxicity. PMID- 1311407 TI - Incorporation of the carbocyclic analog of 2'-deoxyguanosine into the DNA of herpes simplex virus and of HEp-2 cells infected with herpes simplex virus. AB - The carbocyclic analog of 2'-deoxyguanosine (CdG) is active against herpes simplex virus (HSV), human cytomegalovirus, and human hepatitis-B virus. In order to understand the mechanism of action of this compound against HSV, we have evaluated (a) the incorporation of [3H]CdG into viral and host DNA in HEp-2 cells infected with HSV and (b) the interaction of the 5'-triphosphate of CdG (CdG-TP) with the HSV DNA polymerase and human DNA polymerases alpha, beta, and gamma (EC 2.7.7.7). Incubation of HSV-1-infected HEp-2 cells with [3H]CdG resulted in the incorporation of CdG into both the HSV and the host cell DNA. These results indicated that CdG-TP was used as a substrate for HSV DNA polymerase and for at least one of the cellular DNA polymerases. Degradation of both viral and host DNA with micrococcal nuclease and spleen phosphodiesterase indicated that CdG was incorporated primarily into internal positions in both DNAs. The viral DNA containing CdG sedimented in neutral and alkaline sucrose gradients in the same way as did viral DNA labeled with [3H]thymidine, indicating that the HSV DNA containing CdG was similar in size to untreated HSV DNA. CdG-TP was a competitive inhibitor of the incorporation of dGTP into DNA by the HSV DNA polymerase (Ki of 0.35 microM) and the human DNA polymerase alpha (Ki of 1 microM). CdG-TP was not a potent inhibitor of either DNA polymerase beta or gamma. Using DNA-sequencing technology, CdG-TP was found to be an efficient substrate for HSV DNA polymerase. Incorporation of CdG monophosphate (CdG-MP) into the DNA by HSV DNA polymerase did not interfere with subsequent chain extension. These results suggested that the antiviral activity of CdG was due to its incorporation into the DNA and subsequent disruption of viral functions. In contrast, CdG-TP was not as good as dGTP as a substrate for DNA synthesis by DNA polymerase alpha, and incorporation of CdG-MP by DNA polymerase alpha inhibited further DNA chain elongation. PMID- 1311409 TI - [35S]sadopine, a novel high affinity, high specific activity, L-type Ca2+ channel probe: characterization of two equipotent diastereomers with opposite allosteric properties. AB - A novel 35S-labeled dihydropyridine (DHP), 1,4-dihydro-2,6-dimethyl-4-(2 trifluoromethylphenyl)-pyridine-3,5-dic arboxyl-3- [2-(N-tert-butoxycarbonyl-L [35S]methionyl)-aminoethyl]-ester-5-ethyl ester, ([35S]sadopine) (800-1400 Ci/mmol), the respective (+)- and (-)-diastereomers, and unlabeled (+/- )-, (-)-, and (+)-sadopine were synthesized. [35S]Sadopine is an excellent high affinity, high specific activity radioligand to label selectively the DHP receptor of L type Ca2+ channels in tissue sections as well as in membrane fragments. Both diastereomers bind to the DHP receptors in a saturable and reversible manner, with equal, subnanomolar, dissociation constants. Despite their similar affinities, (+)- and (-)-sadopine differ with respect to their kinetic properties [the association and dissociation rate constants are 10-fold higher for (+) [35S]sadopine at 22 degrees] and their allosteric modulation of the phenylaklylamine or benzothiazepine binding domain. (+)-Sadopine is a negative but (-)-sadopine a positive allosteric modulator of (-)-[N-methyl-3H]LU49888 or (+)-cis-[3H] diltiazem binding at 30 degrees. Both diastereomers act as L-type Ca2+ channel blockers in cardiac and smooth muscle cells. Computer-based analysis of the electrostatic potentials of the two diastereomers and calculation of the interaction energies with a hypothetical DHP receptor model predicted not only the similar affinities of (+)- and (-)-sadopine but also their Ca2+ channel blocking effects. The temperature-dependent allosteric differences between the diastereomers suggest that two distinct conformational states of the DHP receptor are stabilized in vitro, both corresponding to a nonconducting state of the channel. Our data indicate that access to the DHP receptor site, but not binding affinity, is a function of the opposite stereochemistry of the sadopine diastereomers. Therefore, labeled and unlabeled (+)- and (-)-sadopine will be useful probes to further characterize the molecular basis of DHP-Ca2+ channel interaction and the pharmacological and physiological significance of the different allosteric conformations of the channel induced by Ca2+ channel-active drugs. PMID- 1311408 TI - Platelet-activating factor stimulates phosphoinositide turnover in neurohybrid NCB-20 cells: involvement of pertussis toxin-sensitive guanine nucleotide-binding proteins and inhibition by protein kinase C. AB - Platelet-activating factor (PAF) is an unusually potent phospholipid known to be produced by neuronal cells and to modulate cerebral blood flow and metabolism. In previous studies with NCB-20 cells, we reported that PAF induced a significant mobilization of intracellular free Ca2+ ([Ca2+]i), which was inhibited by PAF antagonists. The increase was the result of release from intracellular stores and influx from extracellular sources. The present study was designed to characterize further PAF receptor-mediated cellular signal-transduction mechanisms in myo [3H]inositol-labeled cells. PAF induced a concentration-dependent increase in phosphatidylinositol (Pl) metabolism, with EC50 values of 1.96 +/- 0.62 nM and 1.12 +/- 0.50 nM for inositol trisphosphate (IP3) and inositol monophosphate (IP1) formation, respectively (four experiments). The maximal production of IP3 and IP1 induced by 50 nM PAF was 254 +/- 34% and 178 +/- 25% over the basal, respectively (four experiments). PAF-induced Pl metabolism was concentration dependently inhibited by the PAF antagonist BN50739, with an IC50 value of 6.48 +/- 0.52 nM (four experiments). The protein kinase C (PKC) activator phorbol 12,13-dibutyrate concentration-dependently inhibited PAF-induced Pl metabolism and [Ca2+]i mobilization in NCB-20 cells, of NCB-20 cells with pertussis toxin (PTX) resulted in a concentration-dependent inhibition of PAF-induced IP3 production and intracellular Ca2+ release, with a maximal reduction of 66.9 +/- 3.5% and 63 +/- 6.1%, respectively, at 300 ng/ml PTX. PTX in the presence of [32P]NAD specifically [32P]ADP-ribosylated a 38-kDa protein in membranes prepared from NCB-20 cells. Pretreatment of the cells with PTX resulted in a concentration dependent inhibition of subsequent 32P-labeling of the toxin substrate in the membranes and correlated with the uncoupling of PAF-induced IP3 formation. PAF (0.01-10 nM) elicited a concentration-related stimulation in guanosine 5'-O-(3 [35S]) triphosphate ([35S]GTP gamma S) binding to G alpha i(1,2) proteins, which was inhibited by the PAF antagonist BN50739. PAF at 10 nM also increased [35S]GTP gamma S binding to G alpha s and G alpha o. PAF-evoked activation of G alpha i(1,2) and G alpha o was reduced by preincubation with PTX. Our results reveal that neuronal cells possess PAF receptors linked through guanine nucleotide binding proteins to phospholipase C and receptor-operated Ca2+ channels that are regulated by PKC. Both PTX-sensitive and -insensitive guanine nucleotide-binding proteins appear to couple the PAF receptor to activation of phospholipase C and the increase in [Ca2+]i. These results contribute to the further understanding of the mechanisms behind PAF actions on neuronal cells. PMID- 1311410 TI - Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors. AB - In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch clamp technique. Extracellular perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline. The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of 5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and stimulation of cAMP dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin), 5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine. Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5 HT. Thus, the pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent. PMID- 1311411 TI - A2A adenosine receptors from rat striatum and rat pheochromocytoma PC12 cells: characterization with radioligand binding and by activation of adenylate cyclase. AB - Binding assays and assays of activation of adenylate cyclase with the agonists 5' N-ethylcarboxyamidoadenosine (NECA) and CGS21680 have been used to compare adenosine receptors in rat pheochromocytoma PC12 cells and in rat striatum. The [3H]NECA binding showed two components, whereas [3H]CGS21680 bound to one component in both tissues. The Kd value for the high affinity site labeled with [3H]NECA in PC12 cell membranes (2.3 nM) was lower than that in striatum (6.5 nM). The [3H]CGS21680 binding site showed a Kd value of 6.7 nM and 11.3 nM in PC12 cells and striatum, respectively. In the presence of GTP the KD values of [3H]NECA and [3H]CGS21680 for the high affinity site were increased severalfold, whereas the low affinity sites for [3H]NECA were no longer detected with filtration assays. A comparison of the ability of a series of agonists and antagonists to inhibit high affinity binding of [3H]NECA to A2 receptors in PC12 cell and striatal membranes indicated that agonists had higher affinities and antagonists had lower affinities in PC12 cells, compared with affinities in striatal membranes. Analysis of activation of adenylate cyclase in PC12 cell membranes suggested that the dose-dependent stimulation by NECA involved two components, whereas CGS21680 stimulated via one component. The maximal stimulation by NECA significantly exceeded that caused by CGS21680. In intact PC12 cells, NECA caused a greater accumulation of AMP than did CGS21680, as was the case in membranes. In striatal membranes, NECA and CGS21680 showed similar maximal stimulations of adenylate cyclase. Both NECA and CGS21680 were more potent in PC12 cell membranes than in striatal membranes, in agreement with binding data. However, in contrast to binding data, antagonists were not less potent versus stimulation of adenylate cyclase by NECA or CGS21680 in PC12 cell membranes, compared with striatal membranes. In toto, the results suggest that A2A receptors in striatum are virtually identical to the A2A receptors in PC12 cells. But, in addition to an A2A receptor, it appears that a lower affinity functional receptor, probably an A2B receptor, is present in PC12 cells and PC12 cell membranes, whereas such a functional low affinity receptor is not detectable in striatal membrane. PMID- 1311413 TI - Lactosylated high density lipoprotein: a potential carrier for the site-specific delivery of drugs to parenchymal liver cells. AB - Mammalian liver contains two types of galactose receptors, specific for Kupffer or parenchymal cells. Because galactose-specific receptors are largely confined to the liver, galactose-bearing carriers are promising vehicles for the specific delivery of drugs to liver cells. In the present study, high density lipoprotein (HDL), a spherical particle with a diameter of 10 nm, in which a variety of lipophilic drugs can be incorporated, was provided with galactose residues by reductive lactosamination. After injection into rats, lactosylated 125I-HDL was rapidly cleared from the plasma (half-life, less than 1 min). Ten minutes after injection, the liver contained about 95% of the dose, whereas only small amounts of radioactivity were found in other tissues. The hepatic uptake was inhibited by preinjection with N-acetylgalactosamine, which indicates that the hepatic recognition sites are galactose specific. Subcellular fractionation of the liver indicated that recognition of lactosylated HDL is followed by internalization and degradation of the apoprotein in the lysosomes. Liver cells were isolated at 10 min after injection of lactosylated 125I-HDL, and it was found that uptake occurs almost exclusively by parenchymal cells. These cells contained about 98% of the hepatic radioactivity. The liver uptake of the lipid moiety of lactosylated HDL, labeled with [3H]cholesteryl oleate, was identical to that of the 125I-labeled apoproteins, which indicates that the particle is taken up as a unit. Thus, lactosylated HDL is taken up rapidly and selectively by parenchymal liver cells, and it appears that it might be a very effective vehicle for the specific delivery of lipophilic drugs to these cells. PMID- 1311412 TI - Characterization of endothelin-converting enzyme from endothelial cells and rat brain: detection of the formation of biologically active endothelin-1 by rapid bioassay. AB - Using the endothelin-1 (ET-1)-stimulated elevation in cGMP in LLC-PK1 cells as a biological detector system for the conversion of big ET-1 (bET-1) to ET-1, we detected bET-1-converting activities in subcellular fractions from bovine aortic cultured endothelial cells (BAE) and rat brain. Within the particulate fraction of BAE, we detected two activities, at pH 3.4 and pH 5.4-7.4. The latter but not the former activity was inhibited in a concentration-dependent manner by phosphoramidon (approximate IC50, 1 microM) and converted bET-1 to ET-1 at a rate of 0.6 nmol/hr/mg of protein. It could be solubilized from the particulate fraction by detergent treatment. Phosphoramidon-inhibitable converting activity was also detected in the cytosolic fraction of BAE. Within the rat brain, phosphoramidon-inhibitable conversion of bET-1 to ET-1 was detected principally in the cytoskeletal fraction, i.e., that fraction from the membrane that was not solubilized by detergent treatment. These results show the presence of at least two different endothelin-converting enzyme activities in endothelial cells and a third within the rat brain. They also demonstrate the use of LLC-PK1 cells as a rapid assay that permits the sensitive detection and measurement of the formation of biologically active ET-1 from its precursor bET-1. PMID- 1311414 TI - Inhibition by cyclosporine of the production of superoxide radicals. PMID- 1311415 TI - Inside polyomavirus at 25-A resolution. AB - Empty capsids and complete virions of polyomavirus crystallize isomorphously. Here we use difference Fourier analysis of X-ray diffraction data at 25-A resolution from these crystals to obtain an electron-density map of the inside of the virion. The polyomavirus capsid is built from 72 pentamers of VP1 that form three different types of connections in the T = 7d icosahedral surface lattice. Self-assembly of purified recombinant VP1 into capsid-like aggregates has shown that switching of the bonding specificity to form the unanticipated non equivalent connections is an inherent property of the VP1 pentamers. Our map of the inside of the virion displays 72 prongs of electron density extending from the core into the axial cavities of the VP1 pentamers. We identify these prongs with the VP2 and VP3 molecules, which may function to guide the assembly of the highly ordered capsid on the nucleohistone core. The atomic structure of the closely related simian virus-40 capsid has been determined from the high resolution diffraction data. Our polyomavirus map, calculated using all the low resolution diffraction data, shows no indication of regular order inside the spherical core. PMID- 1311416 TI - Electron transfer. Biology's wiring circuits. PMID- 1311417 TI - Nature of biological electron transfer. AB - Powerful first-order analysis of intraprotein electron transfer is developed from electron-transfer measurements both in biological and in chemical systems. A variation of 20 A in the distance between donors and acceptors in protein changes the electron-transfer rate by 10(12)-fold. Protein presents a uniform electronic barrier to electron tunnelling and a uniform nuclear characteristic frequency, properties similar to an organic glass. Selection of distance, free energy and reorganization energy are sufficient to define rate and directional specificity of biological electron transfer, meeting physiological requirements in diverse systems. PMID- 1311419 TI - Clonal expansion of p53 mutant cells is associated with brain tumour progression. AB - Tumour progression is a fundamental feature of the biology of cancer. Cancers do not arise de novo in their final form, but begin as small, indolent growths, which gradually acquire characteristics associated with malignancy. In the brain, for example, low-grade tumours (astrocytomas) evolve into faster growing, more dysplastic and invasive high-grade tumours (glioblastomas). To define the genetic events underlying brain tumour progression, we analysed the p53 gene in ten primary brain tumour pairs. Seven pairs consisted of tumours that were high grade both at presentation and recurrence (group A) and three pairs consisted of low grade tumours that had progressed to higher grade tumours (group B). In group A pairs, four of the recurrent tumours contained a p53 gene mutation; in three of them, the same mutation was found in the primary tumour. In group B pairs, progression to high grade was associated with a p53 gene mutation. A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma. Thus, the histological progression of brain tumours was associated with a clonal expansion of cells that had previously acquired a mutation in the p53 gene, endowing them with a selective growth advantage. These experimental observations strongly support Nowell's clonal evolution model of tumour progression. PMID- 1311418 TI - P-type calcium channels blocked by the spider toxin omega-Aga-IVA. AB - Voltage-dependent calcium channels mediate calcium entry into neurons, which is crucial for many processes in the brain including synaptic transmission, dendritic spiking, gene expression and cell death. Many types of calcium channels exist in mammalian brains, but high-affinity blockers are available for only two types, L-type channels (targeted by nimodipine and other dihydropyridine channel blockers) and N-type channels (targeted by omega-conotoxin). In a search for new channel blockers, we have identified a peptide toxin from funnel web spider venom, omega-Aga-IVA, which is a potent inhibitor of both calcium entry into rat brain synaptosomes and of 'P-type' calcium channels in rat Purkinje neurons. omega-Aga-IVA will facilitate characterization of brain calcium channels resistant to existing channel blockers and may assist in the design of neuroprotective drugs. PMID- 1311420 TI - Immunogenetics. Viruses, cancer and the MHC. PMID- 1311421 TI - A chloride channel widely expressed in epithelial and non-epithelial cells. AB - Chloride channels have several functions, including the regulation of cell volume, stabilizing membrane potential, signal transduction and transepithelial transport. The plasma membrane Cl- channels already cloned belong to different structural classes: ligand-gated channels, voltage-gated channels, and possibly transporters of the ATP-binding-cassette type (if the cystic fibrosis transmembrane regulator is a Cl- channel). The importance of chloride channels is illustrated by the phenotypes that can result from their malfunction: cystic fibrosis, in which transepithelial transport is impaired, and myotonia, in which ClC-1, the principal skeletal muscle Cl- channel, is defective. Here we report the properties of ClC-2, a new member of the voltage-gated Cl- channel family. Its sequence is approximately 50% identical to either the Torpedo electroplax Cl- channel, ClC-0 (ref. 8), or the rat muscle Cl- channel, ClC-1 (ref. 9). Isolated initially from rat heart and brain, it is also expressed in pancreas, lung and liver, for example, and in pure cell lines of fibroblastic, neuronal, and epithelial origin, including tissues and cells affected by cystic fibrosis. Expression in Xenopus oocytes induces Cl- currents that activate slowly upon hyperpolarization and display a linear instantaneous current-voltage relationship. The conductivity sequence is Cl- greater than or equal to Br- greater than I-. The presence of ClC-2 in such different cell types contrasts with the highly specialized expression of ClC-1 (ref. 9) and also with the cloned cation channels, and suggests that its function is important for most cells. PMID- 1311422 TI - US research politics. Goodwin stumbles. PMID- 1311423 TI - Product of vav proto-oncogene defines a new class of tyrosine protein kinase substrates. AB - Several proteins implicated in the regulation of cellular responses to mitogenic stimuli contain a common non-catalytic domain, SH2 (for src-homologous domain 2), that mediates their interaction with activated tyrosine protein kinases. Here we report that p95vav, a proto-oncogene product specifically expressed in cells of the haematopoietic system, contains an SH2 domain and is a substrate for tyrosine protein kinases. Exposure of quiescent NIH3T3 cells ectopically expressing p95vav to either epidermal or platelet-derived growth factors induces the rapid phosphorylation of this protein on tyrosine residues. Activation of the receptors for these growth factors by their cognate ligand results in their association with p95vav, a process mediated by its SH2 domain. In T cells, co-activation of the T-cell receptor and the accessory CD4 cell-surface protein also results in the phosphorylation of the endogenous p95vav protein in tyrosine residues. Phosphorylation of p95vav is rapid, transient and precedes the appearance of most other phosphotyrosine-containing proteins. In addition to the SH2 domain, p95vav contains structural motifs not found in other tyrosine kinase substrates. One such motif is a helix-loop-helix/leucine zipper-like domain which shares some sequence similarity with these motifs in the Myc and Max proteins. Deletion of the helix-loop-helix-like motif causes oncogenic activation of p95vav. These results indicate that p95vav is a new type of signal transduction molecule and suggest a possible role for this protein in the transduction of tyrosine phosphorylation signalling into transcriptional events. PMID- 1311424 TI - The kinetics of the inhibition by dihydroouabain of the sodium pump current in single rabbit cardiac Purkinje cells. AB - The kinetics of the inhibition by dihydroouabain (DHO) of the Na pump current were studied in isolated rabbit cardiac Purkinje cells by means of whole-cell recording. A fast exchange of the extracellular solution at the membrane of the cell studied was performed via two multi-barrelled pipettes nearby. Judging from the steady-state inhibition of the Na pump current at various DHO concentrations half maximal inhibition occurred at 1 x 10(-5) mol/l DHO in a medium containing 2 mmol/l K+ and at 3.5 x 10(-5) mol/l DHO in a solution containing 10.8 mmol/l K+. Assuming a reversible one-to-one binding reaction, the time course of DHO binding and unbinding was analysed under a variety of conditions. It was shown that the antagonistic effect of K+ on the inhibition of the pump current was entirely due to a decrease of the association rate constant of DHO binding to the sodium pump at higher K+ concentrations. The association rate constant amounted to 1 x 10(4) (mol/l)-1.s-1 at 2 mmol/l K+ and to 2.8 x 10(3) (mol/l)-1.s-1 at 10.8 mmol/l K+. The dissociation rate constant of DHO unbinding remained unchanged (approximately 0.06 s-1). The equilibrium dissociation constant KD for the inhibition of the pump current by DHO decreased by a factor 3 to 5 if the Na+ concentration of the patch pipette solution was augmented from 5 to 50 mmol/l. Increasing DHO concentrations inhibited the pump current increasingly faster and to a larger extent. The KD values derived showed little variation with the concentration of DHO applied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311425 TI - Functional role of sodium pump in human placental arteries. AB - Ouabain (10(-7) to 10(-4) M) elicited concentration-dependent contractile responses in human placental arteries. The contractions were reduced by 10(-4) M amiloride and Ca(2+)-free medium, but not affected by 10(-6) M nifedipine or 10( 6) M Bay-K-8644, which markedly reduced or potentiated 75 nM K(+)-induced contractions, respectively. After contracting the vessels with 10(-6) M prostaglandin F2 alpha in a K(+)-free medium, the subsequent addition of 7.5 mM K+ induced a marked relaxation, which was blocked by 10(-6) M ouabain. This glycoside (10(-8) to 10(-4) M) also produced a concentration-dependent reduction of 86Rb+ uptake. Scatchard analysis of the [3H]-ouabain binding to membrane fractions from human placental arteries suggests a single class of binding sites with a KD of 88.3 nM and a Bmax of 345 fmol/mg. 5-Hydroxytryptamine (5-HT; 10(-9) to 10(-5) M) caused concentration-dependent contractions. Single concentrations produced transient responses composed of an initial contraction, followed by a slow fall in tension. Ouabain (10(-8) to 10(-6) M), K(+)-free medium or the reduction of bath temperature (28 degrees C) did not modify contractions but inhibited the relaxant phase of the response. 5-HT (10(-8) to 10(-6) M) increased both total and ouabain-insensitive 86Rb+ uptake, but the difference between them was not modified. These data indicate that: (1) human placental arteries possess an important sodium pump activity, inhibition or stimulation of which markedly alters vascular tone, (2) ouabain-evoked contractions are produced by Ca2+ entry mainly through Na(+)-Ca2+ exchange, secondary to intracellular Na+ accumulation, (3) the relaxant component of 5-HT response is dependent on the activity of the sodium pump, (4) the activation of Na+,K(+)-ATPase activity by this amine is not apparently due to direct effect, and (5) the inhibition of the sodium pump can cause long lasting increases of placental vascular resistance in the presence of physiological concentrations of 5-HT. PMID- 1311426 TI - Isoprenaline-induced increase in the 40/41 kDa pertussis toxin substrates and functional consequences on contractile response in rat heart. AB - Chronic beta-adrenoceptor stimulation leads to desensitization of the myocardial adenylyl cyclase signalling pathway which includes beta-adrenoceptor downregulation and upregulation of Gi-protein alpha-subunits. However, these investigations have mainly been done in cellular preparations. In this study we report that isoprenaline infusion in vivo leads to an increase in myocardial Gi alpha and present evidence for functional consequences of this increase. Rats were treated by a 4-day subcutaneous infusion with isoprenaline (2.4 mg/kg.d), propranolol (9.9 mg/kg.d) and triiodothyronine (T3, 0.5 mg/kg.d) for comparison. Isoprenaline treatment increased the pertussis toxin-sensitive amount of Gi alpha by 22 +/- 6% and decreased beta 1- and beta 2-adrenoceptor density from 35 +/- 4 to 23 +/- 6 fmol/mg protein and 24 +/- 4 to 8 +/- 6 fmol/mg protein, respectively. Contraction experiments on electrically driven papillary muscles revealed that the negative inotropic potency of the M-cholinoceptor agonist carbachol in the presence of isoprenaline was increased as compared to control (mean EC50-values: 0.04 mumol/l vs. 0.28 mumol/l). All isoprenaline-induced effects were antagonized by simultaneously administered propranolol. T3 treatment had no influence on the parameters investigated. The results suggest that chronic beta-adrenoceptor stimulation desensitizes myocardial adenylyl cyclase by at least two mechanisms: beta-adrenoceptor downregulation leading to diminished signal transduction in the stimulatory pathway and Gi alpha upregulation leading to sensitization of the inhibitory pathway. Such adaptation might protect the heart from chronic exposure to catecholamines in heart diseases with elevated plasma catecholamine levels. PMID- 1311427 TI - Comparison of the effects of neuropeptide K and neuropeptide gamma with neurokinin A at NK2 receptors in the hamster urinary bladder. AB - Neuropeptide K (NPK) and neuropeptide gamma (NP gamma) are two endogenous N terminally extended forms of neurokinin A (NKA). Here, we compared their effects with those of NKA on 125I-NKA binding, phosphatidylinositol (PI) turnover and smooth muscle contraction in the hamster urinary bladder. NPK, NP gamma and NKA were equipotent in competing 125I-NKA from NK2 receptors in crude hamster bladder membranes. All three peptides stimulated PI turnover by approximately 750% with similar potency. In a third series of experiments, these peptides had similar efficacy in inducing a dose-dependent contraction of bladder smooth muscle. The NK2 receptor selective antagonist L-659,877 (cyclo[Leu-Met-Gln-Trp-Phe-Gly]) inhibited the stimulation of PI turnover and bladder contractions induced by all three tachykinins. The present results show that NKA, NPK and NP gamma display a similar biological profile. The N-terminal extensions of NPK and NP gamma appear not to influence binding of these peptides to NK2 receptors, NK2 receptor mediated stimulation of PI turnover, or smooth muscle contraction in hamster urinary bladder. PMID- 1311428 TI - Phenytoin partially antagonized L-type Ca2+ current in glucagon-secreting tumor cells (ITC-1). AB - Transmembrane Ca2+ currents were investigated by means of a whole-cell clamp technique in a hamster glucagon-secreting tumor cell line (ITC-1). Two types of Ca2+ current were identified in ITC-1 cells. The low-threshold and transient (T type) current became detectable above the potential level around -60 mV and decayed rapidly with an inactivation time constant of 95 ms (at -40 mV and 23 degrees C), while the high-threshold and long-lasting (L-type) one was activated by depolarization more positive to -30 mV with non-inactivating kinetics. The voltage dependence and kinetics of these currents were identical to those reported in guinea-pig pancreatic alpha 2 cells. Both currents were augmented by equimolar substitution of Ca2+ with Ba2+ and completely abolished by adding 1 microM La3+. Phenytoin, a well known anti-epileptic drug and a postulated T-type specific Ca2+ current antagonist, surprisingly blocked the L-type current without affecting the T-type current in ITC-1 cells. While phenytoin antagonized the L type Ba2+ current selectively, 60% of the current remained even in supramaximal concentration range over 500 microM. The residual component of the L-type current was completely abolished by adding nifedipine. PMID- 1311430 TI - [Surgical treatment of hip fractures in 90-year-olds]. PMID- 1311429 TI - Effect of 3-morpholinosydnonimine (SIN-1) and NG-nitro-L-arginine (NNA) on isolated perfused anaphylactic guinea-pig hearts. AB - The modulating effects of exogenous and endogenous nitric oxide (NO) on the cardiac anaphylactic reaction and eicosanoid release were investigated in isolated perfused sensitized guinea-pig hearts using 3-morpholinosydnonimine (SIN 1), the active metabolite of molsidomine, as NO-donor and NG-nitro-L-arginine (NNA) as an inhibitor of NO biosynthesis. Infusion of SIN-1 (final concentrations in the perfusates 0.3 or 1.0 mmol/l) elevated coronary flow under basal conditions as well as during cardiac anaphylaxis, while NNA (0.1 mmol/l) decreased basal coronary flow and aggravated the anaphylactic coronary constriction. Both drugs did not modify the characteristic biphasic profile of the coronary constriction after antigen challenge with an initial more severe phase followed by a less pronounced long-lasting flow reduction. Neither SIN-1 nor NNA affected spontaneous heart rate. However, while NNA tended to prolong the duration of antigen-induced arrhythmias, SIN-1 (1 mmol/l) had an inhibitory effect. This protection might be related to the increased coronary flow in the presence of SIN-1. SIN-1 inhibited anaphylactic release of cysteinyl-leukotrienes (LT) and 6-keto-prostaglandin (PG) F1 alpha, but did not influence thromboxane (TX) B2 release. On the other hand, NNA (0.1 mmol/l) inhibited anaphylactic release of TXB2, but had only marginal effects on the release of cysteinyl-LT and 6-keto-PGF1 alpha. The results suggest that exogenous and endogenous NO functionally antagonize the effects of vasoconstrictor mediators released after antigen challenge. Additional effects of high concentrations of SIN-1 and NNA on antigen-induced eicosanoid release could modulate the vascular actions of these drugs during cardiac anaphylaxis. PMID- 1311431 TI - Autoradiographic localization of gamma-aminobutyric acidA receptors within the ventral tegmental area. AB - Destruction of intrinsic neurons in the ventral tegmental area (VTA) with the excitotoxin, quinolinic acid produced a significant decrease (80%) in [3H]muscimol binding to GABAA receptors within the parabrachial pigmented and paranigral nuclei of the VTA. Selective destruction of the dopaminergic neurons with 6-hydroxydopamine (6-OHDA) did not reduce [3H]muscimol binding within the VTA. However, the destruction of dopaminergic neurons did produce an increase (20%) in [3H]muscimol binding contralateral to the lesion, suggesting a reduction in the GABAergic innervation to this region. Additionally, destruction of the VTA afferents with quinolinic acid injections in the medial accumbens failed to produce alterations in [3H]muscimol binding within the VTA. These results are consistent with the predominant localization of GABAA receptors to non dopaminergic neurons intrinsic to the VTA. PMID- 1311432 TI - Trophic regulation of acetylcholinesterase isoenzymes in adult mammalian skeletal muscles. AB - This work addresses the physiological regulation of skeletal muscle acetylcholinesterase (AChE) isoforms by examining endplate-enriched samples from adult rat gracilis muscles 48 h after: low-intensity treadmill exercise; obturator nerve transection; nerve impulse conduction blockade by tetrodotoxin; acetylcholine (ACh) receptor (AChR) inactivation by alpha-bungarotoxin; and, addition of obturator nerve extracts to muscles in organ culture. Results document the important role(s) of functional AChRs and ACh-AChR interactions in the differential control of individual AChE isoenzymes. A theoretical model based on these and other findings considers that: AChR activation by spontaneously released ACh is the only neural factor required for the maintenance of G1 + G2 AChE; the amount of A12 AChE is determined by the combined effects of ACh and another neurogenic substance; although mechanisms intrinsic to myofibers control normal levels of G4 AChE, enhanced production of this isoform is initiated through increasing the frequency of ACh-AChR interactions. PMID- 1311433 TI - [3H]D-aspartic acid release in brain slices of adult and aged Fischer 344 rates. AB - Alterations in glutamate content and uptake have been reported to occur in aged animals. The present studies used [3H]D-Aspartic acid [( 3H]-D-ASP) release as a marker for glutamate neurotransmission. Frequency dependent [3H]-D-ASP release was measured in adult (8 month) and aged (28-30 month) Fischer 344 rats. Relatively high stimulation frequencies (greater than 10 Hz) were required to induce [3H]-D-ASP release in both adult and aged F344 rats in temporal cortex and hippocampus. In both brain areas aged animals showed significantly more [3H]-D ASP release than adult animals. Kainic acid 1 mM failed to induce the release of [3H]-D-ASP in either temporal cortex or hippocampus. Omega conotoxin GVIA (5 x 10(-9) M) a N and L type voltage sensitive calcium channel antagonist failed to inhibit [3H]-D-ASP stimulated release. These results demonstrate an increase in [3H]-D-ASP release in aged compared to adult F344 rats. The data also suggest a novel calcium channel may be involved in [3H]-D-ASP release. PMID- 1311434 TI - gamma-Hydroxybutyric acid binding sites: interaction with the GABA-benzodiazepine picrotoxin receptor complex. AB - The effect of three compounds known to allosterically modulate binding to the GABA/benzodiazepine/picrotoxin receptor complex on 4-hydroxy-2,3 [3H]butyric acid (GHB) binding was investigated. Pentobarbital, pentylenetetrazole, and picrotoxin enhanced [3H]GHB binding in a dose dependent fashion. Pentobarbital enhanced 4 hydroxy-2,3 [3H]butyric acid binding was associated with an increase in Bmax while pentylenetetrazole and picrotoxin altered the affinity of GHB for its binding site producing a decrease in Kd. These findings suggest that the GHB and GABA receptor complex may share certain moieties in common. PMID- 1311436 TI - Protection of cisplatin-induced neuropathy: recent developments. PMID- 1311435 TI - Effects of selected vasoactive substances on adenylate cyclase activity in brain, isolated brain microvessels, and primary cultures of brain microvessel endothelial cells. AB - The specific activity of adenylate cyclase was assayed in homogenates of gray matter, freshly isolated and primary cultured microvessel endothelial cells from bovine cerebral cortex. Specific activities for the tissues were 14.6 +/- 2.1, 15.6 +/- 2.7, and 8.4 +/- 1.5 pmol cAMP/mg protein/min +/- SD for gray matter, cultured microvessels, and freshly isolated microvessels, respectively. Adenylate cyclase associated with gray matter and cultured microvessels was sensitive to histamine and selected catecholamines. Perhaps due to metabolic deficiencies, adenylate cyclase of freshly isolated microvessels exhibited little or no response to either the catecholamines or histamine. Angiotensin II stimulated adenylate cyclase of both freshly isolated and cultured microvessels but had no effect on gray matter. Bradykinin did not stimulate cAMP generation in any of the tissues. Overall results support the role of cAMP in regulating brain microvessel functions and suggest that primary cultures of brain microvessels may be useful in examining cAMP-mediated biochemical pathways at the blood-brain barrier. PMID- 1311437 TI - [Efficacy and tolerance of dideoxynucleosides in HIV infection]. PMID- 1311438 TI - [Nutrition and cancer]. PMID- 1311439 TI - [Natural history of chronic viral hepatitis]. PMID- 1311440 TI - [Histopathology of hepatocellular carcinoma]. PMID- 1311441 TI - Epidemiology of hepatocellular carcinoma in the West. PMID- 1311442 TI - [Non surgical treatments of hepatocellular carcinoma]. PMID- 1311443 TI - [Populations and individuals at risk for colorectal cancer]. PMID- 1311445 TI - [Hodgkin's disease. Genetic factors or environmental factors?]. PMID- 1311444 TI - [Colorectal cancers and molecular biology]. PMID- 1311446 TI - [Phase II trial of concomitant cyclic radio-chemotherapy combination (ARCCC) in unoperable non-small cell lung cancer (CBNPCI)]. PMID- 1311447 TI - [Advances in the treatment of non-small cell lung cancer]. PMID- 1311448 TI - [Advances in the treatment of small cell lung cancer]. PMID- 1311449 TI - The use of GM-CSF as adjunctive therapy in small cell lung cancer. Presentation of the interim analysis of a large phase II trial. PMID- 1311450 TI - Efficacy of hydrated sodium calcium aluminosilicate to reduce the individual and combined toxicity of aflatoxin and ochratoxin A. AB - A 2 x 2 x 2 factorial arrangement of treatments consisting of dietary aflatoxin (3.5 micrograms/g), ochratoxin A (2.0 micrograms/g), and hydrated sodium calcium aluminosilicate (HSCAS, .5%) was used to evaluate the individual and combined effects of these treatments. There were six replicate pens of 10 broilers per pen for each of the eight treatments. The broilers were maintained on these treatments from 1 day to 3 wk of age with feed and water available for ad libitum intake. Aflatoxin and ochratoxin A each significantly decreased body weight, serum protein, albumin, and cholesterol and increased the relative weight of the liver, kidney, and proventriculus. Aflatoxin increased the relative weight of the heart and decreased serum aspartate aminotransferase activity and ochratoxin A increased serum uric acid. The toxicity resulting from the combination of aflatoxin and ochratoxin A was more severe than when either of these mycotoxins were present alone. Addition of HSCAS alone did not alter any of the parameters evaluated. The HSCAS reduced the toxicity of aflatoxin, but had little effect on either the toxicity of ochratoxin A alone or the toxicity resulting from the combination of aflatoxin and ochratoxin A. PMID- 1311451 TI - Regulation of steroid hormone action in target cells by specific hormone inactivating enzymes. AB - The target cell sensitivity of steroid hormones is determined by the concerted action of specific hormone receptors and steroid-inactivating enzymes. In recent years, a considerable amount of knowledge has been obtained on hormone receptor concentration-based target cell sensitivity. However, an equal understanding of the role of specific steroid-inactivating enzymes in hormone action is absent. This review highlights the importance of specific steroid-inactivating enzymes in the control of target cell sensitivity of mineralocorticoids, glucocorticoids, androgens, and estrogens. Two classes of enzymes that are actively involved in this process are hydroxysteroid dehydrogenases and hydroxysteroid sulfotransferases. Some of the target cells in which the critical roles of these enzymes have been extensively characterized are those of the kidney, endometrium, and liver. cDNA for many of these enzymes have already been cloned, and rapid progress in the elucidation of this component of steroid hormone action is anticipated. PMID- 1311452 TI - Effects of dietary fermentable fiber on fatty acid synthesis and triglyceride secretion in rats fed fructose-based diet: studies with sugar-beet fiber. AB - In an attempt to elucidate the role of the dietary fermentable fiber in reduction of hyperlipidemia, we substituted 30% wheat starch with 30% sugar-beet fiber in rats fed a fructose-based (41% fructose), low-fat (2% corn oil) diet. Male Wistar rats ate the test diets for 3 weeks. Feeding the sugar-beet fiber (SBF) diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids compared with rats fed a fiber-free (FF) diet. Feeding SBF decreased plasma triglyceride and cholesterol concentrations in the postprandial as well as the postabsorptive period. In the liver, triglyceride levels were depressed in concert with the decreased liver lipogenesis and the post-Triton triglyceride secretion. Liver cholesterol levels were unaffected by SBF diet feeding. SBF-fed animals were markedly less fat compared with fiber-free diet-fed rats. Adipose tissue lipogenesis was depressed in the postprandial period in SBF-fed animals. In short, this study suggests that substitution of easily digested carbohydrates by certain fermentable fibers may play an interesting role in the reduction of hyperlipidemia and obesity. PMID- 1311453 TI - Diazepam impairs retention of spatial information without affecting retrieval or cue learning. AB - We further investigated the effect of diazepam on the processing of spatial information in a water maze task. Diazepam significantly impaired the retention of spatial information in a group of rats trained to locate a hidden platform. In a free swim trial carried out after training, diazepam-treated rats showed no bias to the target quadrant. There was no effect of diazepam on retrieval of spatial information in well-trained rats, and diazepam was devoid of any effect on cue learning in the water maze. However, diazepam blocked latent place learning during cue training in the water maze. Our results indicate that the GABA-BZD receptor modulates spatial information processing and that diazepam specifically impairs the retention of spatial information without affecting retrieval or cue learning. PMID- 1311454 TI - Effects of [D-Ala2, D-Leu5]enkephalin and [D-Pen2, L-Pen5]enkephalin on apomorphine-induced motor activity in the mouse. AB - The effects of intracerebroventricular injections of opioid peptides such as DADL [( D-Ala2, D-Leu5]enkephalin) and DPLPE [( D-Pen2, L-Pen5]enkephalin) with different degrees of selectivity for delta- over mu-receptor on apomorphine (0.1, 0.3, 1.0 and/or 3.0 mg/kg)-induced motor activity were investigated in the mouse using multi-dimensional behavioral analyses. Lower doses (0.1 and 0.3 mg/kg) of apomorphine failed to affect significantly motor activity, whilst higher doses (1.0 and 3.0 mg/kg) of the drug produced a marked increase in linear locomotion, circling, rearing, and/or grooming behaviors. DADL (0.03, 0.1 or 0.3 microgram) by itself did not influence behaviors, while the peptide (0.1 and 0.3 microgram) produced a marked inhibition on apomorphine (1.0 but not 3.0 mg/kg)-induced increase in rearing behaviors. Furthermore, the inhibitory effect of DADL (0.3 micrograms) on the apomorphine (1.0 mg/kg)-induced increase in rearing was reversed by treatment with the alkylating agent beta-FNA (beta-funaltrexamine) (5.0 micrograms). In contrast to the effects of DADL, the much more delta selective opioid agonist DPLPE (0.3, 1.0 or 1.75 micrograms) had no marked effects on apomorphine (1.0 mg/kg)-induced behaviors. These results suggest that delta opioid receptors do not play a principal role in the apomorphine-induced increase in circling, rearing or grooming behaviors. PMID- 1311456 TI - Effects of acute and chronic ketocyclazocine and its modulation by oxytocin or vasopressin on food intake in rats. AB - The effects of acute and chronic ketocyclazocine (KCZ, a kappa receptor agonist) and its interactions with oxytocin (OXY) or vasopressin (AVP) were investigated on food intake in free-fed rats. Acute treatment with KCZ (1 mg/kg) produced a generalized hyperphagia during the light phase (0-6 h) without influencing dark phase (6-24 h) food intake. On chronic administration, tolerance developed to hyperphagic effect during light phase, whereas an enhancement in the food intake was seen during dark phase. OXY or AVP (both at 10 micrograms/kg) per se, did not affect the food intake response during either the light or the dark phase, after acute as well as chronic treatment. In the interaction studies, acute AVP or OXY attenuated the hyperphagia of KCZ during the light phase. On chronic treatment, both AVP and OXY blocked (a) the tolerance, and (b) the "reverse tolerance" to the food intake response to KCZ during light and dark phases, respectively. These results are discussed in light of complex opioid-OXY/AVP interactions during food intake in rats. PMID- 1311455 TI - Cocaine binding sites in mouse striatum, dopamine autoreceptors, and cocaine induced locomotion. AB - BALB/cByJ mice received cocaine (25 mg/kg IP) once a day for 3 days, resulting in a greater locomotor response to cocaine on day 3 than on day 1. On day 4, a dose (0.03 mg/kg SC) of apomorphine, targeted at dopamine autoreceptors, caused the same degree of locomotor depression in cocaine- as in saline-pretreated mice. In addition, no change was found in either the affinity or density of cocaine binding sites in their striatum as measured by the binding of [3H]CFT. C57BL/6ByJ, mice displayed a greater locomotor response to cocaine than BALB/cByJ mice, but had the same number of striatal [3H]CFT binding sites with the same affinity. Factors other than striatal cocaine binding sites, or dopamine autoreceptors as measured by apomorphine-induced depression of locomotion, should be considered for the explanation of the enhancement of the locomotor response upon daily cocaine administration in BALB/cByJ mice, or for the different locomotor response to cocaine of this strain compared with the C57BL/6ByJ strain of mice. PMID- 1311457 TI - Emotional arousal-induced transient global amnesia. A clue to the neural transcription of emotion? PMID- 1311458 TI - The regulation of connective tissue metabolism by vasoactive intestinal polypeptide. AB - Immunohistochemical studies have confirmed the innervation of bone with neuropeptidergic neurons containing vasoactive intestinal polypeptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). In this study, we report effects of VIP on connective tissue cell metabolism. VIP stimulated PGE2 production in human articular chondrocytes, human osteoblast-like cells and human synovial cells, however, stromelysin production was unaffected. VIP also stimulated cAMP production in human osteoblast-like cells, but not in human articular chondrocytes or synovial cells. These findings are suggestive of a role of VIP in connective tissue cell metabolism which may contribute to the inflammatory processes of arthritis. PMID- 1311459 TI - Heterogeneity of NK-2 tachykinin receptors in hamster and rabbit smooth muscles. AB - The possible existence of NK-2 receptor subtypes in peripheral smooth muscle preparations from rabbit and hamster was investigated by studying the effect of neurokinin A, the selective NK-2 receptor agonist [beta Ala8] neurokinin A (4 10), the selective NK-2 tachykinin receptor antagonists, MEN 10,376, L 659,877 and R 396, and the pseudopeptide derivative of neurokinin A (4-10), MDL 28,564. All experiments were performed in the presence of peptidase inhibitors (captopril, bestatin and thiorphan, 1 microM each). Both neurokinin A and [beta Ala8] neurokinin A (4-10) produced concentration-dependent contractions of the rabbit isolated bronchus and hamster isolated stomach and colon, as well as enhancement of the nerve-mediated twitches of rabbit isolated vas deferens (pars prostatica). MEN 10,376, L 659,877 and R 396 antagonized the effect of the NK-2 receptor selective agonist in all four tissues under study, although marked differences in antagonist potency were evident for the three antagonists. Thus MEN 10,376 was distinctly more potent (about 100 times) in rabbit than in hamster preparations while L 659,877 and R 396 were more potent in hamster than rabbit preparations. MDL 28,564 showed a distinct agonist character in rabbit preparations while it was virtually inactive in hamster preparations, where it antagonized the effect of the NK-2 receptor selective agonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311460 TI - [Oat bran as lipid-lowering agent?]. AB - Hypercholesterolemia is one of the major risk factors for ischemic heart disease and for the development of atherosclerotic plaques. Water soluble plant fibers do exert a binding of intestinal cholesterol and are not digested or metabolized. We have investigated the effect of a highly water soluble fiber containing oat brain on serum cholesterol concentrations in 14 volunteers (nine males, five females, age 39 to 67 years, serum cholesterol concentration: 7.14 +/- 0.80 mmol/l; x +/- SD) during an intervention with 50 g oat brain per day for nine weeks. We have documented in the whole study population a modest, but significant reduction of serum cholesterol levels of 4.2% (p less than 0.05) at six weeks; however at nine weeks the efficacy of this regimen was less pronounced (3.2%, p = n.s.) speaking for a decreased compliance although this regimen was well tolerated and accepted. In subsets of high risk volunteers for coronary heart disease of male gender (n = 9), with hypercholesterolemia (n = 8) or essential hypertension (n = 8) the reduction of serum cholesterol levels was more consistent (5.6%, p less than 0.05) with no change in normolipemic volunteers. PMID- 1311461 TI - [A case from practice (236). 1. Fulminant hepatitis B. 2. Carrier of HCV antibodies. 3. Intravenous drug abuse]. PMID- 1311462 TI - The practice of cardiothoracic surgeons in the perioperative staging of non-small cell lung cancer. PMID- 1311463 TI - The practice of cardiothoracic surgeons in the perioperative staging of non-small cell lung cancer. AB - BACKGROUND: The treatment and prognosis of non-small cell lung cancer, and assessment of the results of treatment, depend on accurate perioperative staging. The extent to which this is carried out in the United Kingdom is unknown. METHODS: A postal questionnaire survey was undertaken in 1990 to determine the perioperative staging practices of cardiothoracic surgeons in the United Kingdom. RESULTS: Replies from 77 surgeons, who between them performed about 4833 pulmonary resections a year for lung cancer, were analysed. Forty four per cent of surgeons, operating on 43% of the patients, do not perform computed tomography of the thorax or mediastinal exploration before surgery. They may therefore embark on a thoracotomy for stage III disease. At thoracotomy 45% of surgeons, operating on 40% of patients, do not sample macroscopically normal lymph nodes. They may therefore understage cases as N0/N1 when there is at least microscopic disease in mediastinal lymph nodes. CONCLUSIONS: The staging of lung cancer in the United Kingdom in 1990 appears in many instances to be inadequate. There should be a more organised approach to perioperative staging so that prognosis may be assessed and comparisons between groups of patients can be made. PMID- 1311464 TI - Cisplatin-induced loss of kidney copper and nephrotoxicity is ameliorated by single dose diethyldithiocarbamate, but not mesna. AB - Platinum, copper, and zinc concentrations in kidney and liver were monitored following administration of cis-diamminedichloroplatinum (Cisplatin, CDDP) alone or in combination with diethyldithiocarbamate (DDC) or mercaptoethanesulfonate (mesna). Compounds were administered in saline to F344 female rats as single bolus ip doses: 7.5 mg CDDP/kg body wt; 500 mg DDC/kg body wt 1 hr after CDDP; and 100 mg mesna/kg body wt 1 hr before CDDP, at the same time as CDDP, or 1 hr after CDDP. Tissues were collected at 4 hr, 1 day, 4 days, and 7 days post-CDDP dosing. CDDP alone produced significant increases in blood urea nitrogen (fourfold) and plasma creatinine (threefold) concentrations by Day 4. Concurrent with the toxicity, CDDP lowered kidney copper (-71%) by Day 4, but had little effect on liver copper except in copper-pretreated rats. Copper-pretreated rats initially had a twofold higher kidney copper concentration and a fourfold higher liver copper concentration, but by Day 4, CDDP lowered copper concentrations in both organs to near the noncopper-treated levels. Platinum in kidney and liver rose 72-100% of peak levels within 4 hr post-CDDP and was relatively stable throughout the 7-day test period. Kidney zinc rose significantly by day 4 only in CDDP-treated rats. DDC protected against the kidney toxicity of CDDP and markedly changed kidney copper loss. Within 4 hr, DDC reduced kidney copper 60% while increasing kidney platinum to the highest concentration of any of the treatments. By Day 4, DDC-treated rats had approximately 50% lower kidney platinum while copper returned toward control levels. A single dose of mesna did not significantly protect against CDDP nephrotoxicity and had little effect on kidney platinum, copper, or zinc. The patterns of copper loss and toxicity from CDDP alone or with DDC suggest that copper be further evaluated for its role in the mechanism of CDDP cytotoxicity. PMID- 1311465 TI - Comparison of oxidant-generation and BP-diol activation by bone marrow cells from C57Bl/6 and DBA/2 mice: implications for risk of bone marrow toxicity induced by polycyclic hydrocarbons. AB - Neutrophil-derived oxidants have been implicated in both the damage to biomolecules and the metabolic activation of xenobiotics. Bone marrow, a relatively neutrophil-rich tissue with low cytochrome P450 activity, is subject to toxicity from orally administered benzo[a]pyrene (BP) in mice with noninducible P450 monooxygenase systems. Thus, we have compared the oxidant generation and chemical activation by neutrophilic cells isolated from femurs of male DBA/2 and C57Bl/6 mice, strains that are susceptible and nonsusceptible, respectively, to bone marrow toxicity from BP. Oxidant generation of neutrophilic preparations was assayed by superoxide anion generation and oxidant-dependent chemiluminescence (CL) from luminol or lucigenin. In all assays, cells from DBA/2 mice demonstrated increased oxidant generation. CL from BP-7,8-dihydrodiol (BP diol) has previously been shown to correlate with its ability to elicit genotoxic effects. A twofold enhancement of oxidant-dependent CL from BP-diol was observed with TPA-stimulated neutrophilic cells from DBA/2 mice as compared to cells from C57Bl/6 mice. DBA/2-derived bone marrow cells also activated more BP-diol to a DNA covalent binding species than did bone marrow cells derived from the less BP sensitive C57Bl/6 mouse. Tetraol analysis of BP-diol metabolism by activated bone marrow cells confirmed this greater bioactivation of the diol by DBA/2-derived cells. These results suggest that the increased risk of DBA/2 mice for BP-induced bone marrow toxicity may be related to their greater ability to bioactivate xenobiotics through oxidant-dependent mechanisms. PMID- 1311466 TI - Meso-2,3-dimercaptosuccinic acid (DMSA) affects maternal and fetal copper metabolism in Swiss mice. AB - Meso-2,3-dimercaptosuccinic acid (DMSA) is a chelating agent used to treat heavy metal intoxication. DMSA has been reported to be teratogenic in the mouse, and it has been suggested that this teratogenicity may be secondary to DMSA-induced alterations in Zn metabolism. In the present study, 0, 400 or 800 mg DMSA/kg body weight were administered on gestation days 6-15 to pregnant Swiss mice by gavage (PO) or subcutaneous injection (SC). Mice were fed a diet containing 14 micrograms Zn, 10 micrograms Cu, 120 micrograms Fe, 1175 micrograms Mg and 6.8 mg Ca/g diet. A sub-group of mice in the 800 mg DMSA/kg SC group was fed a diet containing 250 micrograms Zn/g. DMSA administration did not result in overt maternal toxicity. There was no effect of the drug on fetal or placental weight, or on crown-rump length. However, some fetuses from DMSA-treated dams were characterized by skeletal abnormalities including supernumerary ribs, unossified anterior phalanges and malformed sternebrae. Drug exposure was not associated with consistent changes in tissue Zn, Fe, Ca or Mg levels. Supplemental Zn had no marked effects on the fetus. Fetal liver Cu concentrations exhibited dose dependent decreases with increasing DMSA dose. This finding suggests that the developmental toxicity of DMSA may be mediated through disturbed maternal/fetal copper metabolism. PMID- 1311467 TI - Trichothecene mycotoxins inhibit phosphoinositide hydrolysis in bovine platelets stimulated with platelet activating factor. AB - The effects of the trichothecene mycotoxins, acetyl T-2 toxin, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON) and T-2 tetraol on phospholipid turnover were determined in bovine platelets prelabelled with [1 14C]arachidonic acid (AA). In resting, non-stimulated platelets exposed to acetyl T-2 toxin, a marked decrease in [1-14C]phosphatidylinositol (PI) along with a marked increase in [1-14C]phosphatidic acid (PA) were observed, whereas T-2 toxin, and HT-2 toxin only induced a significant increase in [1-14C]PA. In contrast, in platelet activating factor (PAF)-stimulated platelets, the mycotoxins were found to suppress both the agonist-induced loss of [1-14C]PI and the appearance of [1-14C]PA with acetyl T-2 toxin being the most effective and T 2 toxin, HT-2 toxin, and DAS essentially equally effective. T-2 tetraol and DON did not affect phospholipid metabolism either in unstimulated or PAF stimulated platelets. The alterations in [1-14C]PI and [1-14C]PA suggest that the inhibitory toxins may activate a specific phospholipase C (PLC) in the unstimulated platelets and then impede further PLC activation in PAF-stimulated platelets. PMID- 1311468 TI - Glutathione release by pulmonary alveolar macrophages in response to particles in vitro. AB - We studied whether cultured rat pulmonary alveolar macrophages (PAM) could release glutathione (GSH) in response to latex beads, quartz, and crocidolite asbestos. PAM were exposed for 2 h to 0-100 micrograms of particles per 1 x 10(6) cells. Both quartz and asbestos produced concentration-dependent increases (up to 8-10-fold) in the amount of GSH recovered in the medium and decreases in the cellular GSH levels. In contrast, latex beads did not produce any changes in GSH levels. We also measured lactate dehydrogenase (LDH) levels as an index of toxicity. Only quartz and asbestos were able to produce increases in LDH levels in the medium. The release of GSH occurred at particle concentrations that did not cause release of LDH. Our results indicated that, in vitro, PAM release GSH in response to toxic particles. PMID- 1311469 TI - Inhibition of CD27 expression by cyclosporine A; role of IL-2. PMID- 1311470 TI - Plasma levels of leukotriene B4 during hepatic allograft rejection. PMID- 1311471 TI - Does CMV infection affect the outcome of renal allografts? PMID- 1311472 TI - Anti-CMV hyperimmune globulin prophylaxis does not prevent CMV disease in CMV negative renal transplant patients. PMID- 1311473 TI - CMV infection in various cell types of human kidney. PMID- 1311474 TI - Adenovirus infection in a renal transplant patient. PMID- 1311475 TI - Does acute rejection correlate with infection in liver transplantation? PMID- 1311476 TI - Quantitative protein determination in urine: diagnostic value in renal transplant patients. PMID- 1311477 TI - Allogeneic bone marrow transplantation: the Huddinge experience. PMID- 1311478 TI - Strong donor mononuclear cell reactivity for herpes simplex virus antigen in immune donor/recipient pairs is associated with acute graft-versus-host disease. PMID- 1311479 TI - Liver transplantation in primary liver malignancy. PMID- 1311480 TI - Female sex hormone, estradiol, antagonizes the immunosuppressive activity of cyclosporine in rat organ transplantation. PMID- 1311481 TI - Colorimetric nonisotopic method for in situ hybridization detection of cytomegalovirus in renal allograft biopsies. PMID- 1311482 TI - Reinfection or reactivation of cytomegalovirus infection in renal transplantation. PMID- 1311483 TI - [Cushing's syndrome and pregnancy: apropos of a case and review of the literature]. AB - The occurrence of Cushing's syndrome during pregnancy is rare. Sixty-eight cases have been reported in the literature of which 42.7% were secondary to an adrenal adenoma, 10.2% to an adrenal carcinoma, 26.5% to a bilateral adrenal hyperplasia and 11.8% to Cushing's disease. We report the case of a patient in whom the diagnostic of Cushing's syndrome with an adrenal adenoma was established during the postpartum period. PMID- 1311484 TI - Primary oat cell (neuroendocrine) carcinoma of the breast. Report of four cases. AB - Four cases of oat cell (neuroendocrine) carcinoma of the breast are reported. Three patients died within 15 months of the diagnosis and the fourth patient is alive after 44 months. Histochemical, ultrastructural and mRNA markers of endocrine differentiation were present in three cases. These tumours show histological similarities to breast metastases of bronchial oat cell carcinoma, but a distinguishing feature is the presence of in situ ductal lesions. It appears that the breast is a further site which has to be added to the long list of extrapulmonary oat cell carcinomas. PMID- 1311485 TI - Smooth muscle contraction bands in intestinal infarction. AB - We studied microscopic sections of 24 cases of intestinal infarction looking for contraction bands (CB) in the muscularis propria of the bowel wall. Controls were 11 surgical and 11 autopsy cases from patients who did not suffer any form of ischaemic disease. The difference of CB frequency was significant (P less than 0.001) in infarction versus the surgical control group. Moreover, within the study group the CB frequency was also related to the severity of the ischaemic lesion (P less than 0.01). With immunostaining, CB were not reactive with antibodies against vimentin, desmin, actin or myosin. We propose that CB genesis in intestinal smooth muscle is related to hypoxia, possibly through altered homeostasis of calcium and catecholamine metabolism. PMID- 1311486 TI - Immunohistochemical study of skin lesions in herpes zoster. AB - Thirty-seven biopsy skin tissues of herpes zoster taken from 27 patients were analysed immunohistochemically using two monoclonal antibodies detecting either nucleocapsid or glycoproteins of varicella-zoster virus (VZV) on paraffin sections of formalin fixed tissues. Skin lesions of herpes zoster were divided clinically into four stages: erythematous, vesicular, pustular and ulcerative. In the erythematous stage, VZV antigens, if detected, were found only within ballooning cells in the lower epidermis or follicular epithelium. In the vesicular stage, antigens were detected in the cells around and within the intraepidermal vesicles and in histiocytes or fibrocytes of the dermis in all cases and in the endothelial or perineural cells in 10 of 14 cases. In the pustular stage, the antigens were observed in degenerated or necrotic keratinocytes and multinucleated giant cells within pustules and some necrotic cells in the dermis. In the ulcerative stage, the viral antigens were detected only at the ulcer margin and around the hair shaft in 2 of 7 cases. These results suggest that VZV initially involves the epidermis in the erythematous stage, subsequently invades the dermis in the vesicular stage, and disappears in the early ulcerative stage. PMID- 1311487 TI - Protective efficacy of virus-like particles for bluetongue disease. AB - Bluetongue virus-like particles (VLPs) derived from multiple baculovirus expression vectors have been administered in the presence of various adjuvants to sheep, a vertebrate host susceptible to the virus, and the neutralizing antibody responses are measured. Vaccinated sheep are challenged after 4 months of inoculation, and clinical reaction indices and viraemia determined. The results indicate that these multiprotein virus-like particles lacking the genetic material are highly immunogenic and as little as 10 micrograms of VLPs in conjunction with appropriate adjuvant elicit an immune response which protects against infectious virus challenge. The formation of virus-like particles using this new technology offers a novel approach in vaccinology. PMID- 1311488 TI - Construction of a genetically defined Salmonella typhi Ty2 aroA, aroC mutant for the engineering of a candidate oral typhoid-tetanus vaccine. AB - The construction of a Salmonella typhi Ty2 strain harbouring defined deletions in both the aroA and aroC genes is described. These deletions have been fully defined at the molecular level by DNA sequencing and have been introduced in such a way that no foreign DNA remains in the S. typhi genome. This strain is attenuated in mice when given by the intraperitoneal route suspended in hog gastric mucin and is attenuated to a similar level to strains harbouring deletions in aroA or aroC alone indicating that both lesions are capable of attenuating independently. We have used this defined S. typhi aroA aroC strain to express stably a non-toxic 50 kDa fragment of tetanus toxin (fragment C) from a gene incorporated into the chromosome. This strain has the advantage of harbouring no antibiotic-resistance markers and we consider it to be a candidate bivalent oral typhoid-tetanus vaccine. PMID- 1311489 TI - Potential use of non-replicating vectors as recombinant vaccines. AB - Avipoxviruses, members of the Poxvirus family, are naturally restricted in that productive replication takes place only in avian species. Recent work has described the construction of Avipox recombinants using fowlpox and canarypox viruses. Preparation of recombinant fowlpox viruses which express immunogens from avian pathogens and successful vaccination of poultry have been reported. Recombinant fowlpox and canarypox viruses which express immunogens from mammalian pathogens have also been described and have been demonstrated to provide protective immunity on inoculation in non-avian species. This is a surprising result. Such non-replicating expression vectors provide the possibility of developing safe, effective vaccines which combine the advantages of killed and live vaccines. PMID- 1311491 TI - Immune response of infants to inactivated poliovirus vaccine injected intradermally. PMID- 1311490 TI - Induction of anti-viral immune responses by immunization with recombinant-DNA encoded avian coronavirus nucleocapsid protein. AB - Immune responses to the infectious bronchitis virus (IBV) nucleocapsid protein were studied using a recombinant-DNA expression product. In mice, a lymphocyte proliferative response and a delayed-type hypersensitivity reaction to IBV were induced upon immunization with this nucleocapsid protein. Next, we studied the role of the expressed nucleocapsid protein in induction of a protective immune response to IBV in chickens. Chickens were primed with nucleocapsid protein and subsequently boosted with inactivated IBV, strain M41. Proliferative responses of blood mononuclear cells corresponded with increased mean haemagglutination inhibition and virus neutralization titres. Finally, an increased tracheal protection against challenge with live IBV was observed. These results indicate that infectious bronchitis virus nucleocapsid protein is a relevant target for immune recognition in both the mouse and the chicken. PMID- 1311492 TI - Current progress towards vaccines for arenavirus-caused diseases. AB - The arenaviruses are primarily viruses of rodents, but some members of the group cause severe disease (Argentine and Bolivian haemorrhagic fevers and Lassa fever) when transmitted to humans in the specific areas of the world where they are enzootic. Current research of relevance to the provision of vaccines against these diseases, which highlights many of the problems encountered generally in the development of vaccines, is reviewed here. Although one of the classical approaches to vaccine production, the use of inactivated preparations of virus of varying degrees of purity, has produced no results of promise, attenuation of a virulent strain of Junin virus by passage in cultured cells has yielded a vaccine strain currently being tested for efficacy in protecting against Argentine haemorrhagic fever in the human population at risk. The experimental evidence for protection in animal model systems by related, apparently non-pathogenic, viruses and by recombinant vaccinia viruses expressing arenavirus proteins is discussed, together with some of the potential difficulties of these approaches. PMID- 1311493 TI - In vivo potentiation of atracurium neuromuscular blockade by nimodipine in rabbits. AB - The interaction between nimodipine, a calcium channel blocker, used for the treatment of subarachnoid haemorrhage, and atracurium, was studied in rabbits. An intravenous dose of 0.1 mg.kg-1 of nimodipine given over 3 min caused a potentiation of the neuromuscular blocking action of atracurium (administered at an infusion rate of 7.5 micrograms.kg-1.min-1), measured on the indirectly stimulated tibialis-anterior muscle of the animal. (ED50)inf and (ED95)inf were significantly reduced (30.7% and 23.3%) in nimodipine-treated animals (P less than 0.05 and P less than 0.02, respectively). No changes were observed in recovery rate. PMID- 1311494 TI - Effect of guar, pectin, psyllium, soy polysaccharide, and cellulose on breath hydrogen and methane in healthy subjects. AB - Different types of dietary fiber are fermented to various extents in vitro, but little is known about the effects of fiber on breath hydrogen and methane levels in vivo. Therefore, we studied the effects on breath hydrogen and methane of 15 g of guar, pectin, psyllium, soy polysaccharide, or cellulose in eight healthy subjects over a 12-h period. None of the fibers had a significant effect on breath hydrogen or methane concentrations, compared with the control (fasting). The four methane producers had lower breath hydrogen levels than the nonproducers 1 h after 15 g of lactulose (3 +/- 1 vs. 42 +/- 9, p less than 0.005) and 5-12 h after the different fibers (3.3 vs. 4.8 ppm; pooled SEM = 0.8; p less than 0.025). When the methane responses of the methane producers were expressed as increments relative to the control, there were small differences between treatments, with guar producing a larger response, 8.2 +/- 3.3 ppm, than cellulose, -2.9 +/- 2.3 ppm (p less than 0.05). The incremental methane responses of the different fibers in vivo were related to the previously reported production of propionic acid (r = 0.94, n = 5, p less than 0.02) and methane (r = 0.93, n = 4, NS) from in vitro fermentation of the same fibers. We conclude that methane producers have lower breath hydrogen levels than nonproducers. Purified fermentable and nonfermentable dietary fibers have no effect on breath hydrogen levels over 12 h in subjects previously consuming a normal diet. However, fermentable fibers may produce small increases in breath methane in methane producing subjects. PMID- 1311495 TI - Assignment of the urokinase-type plasminogen activator receptor gene (PLAUR) to chromosome 19q13.1-q13.2. AB - The urokinase-type plasminogen activator receptor (uPAR) is a key molecule in the regulation of cell-surface plasminogen activation and, as such, plays an important role in many normal as well as pathological processes. We applied a cDNA probe from the corresponding gene (PLAUR) in a location analysis using a panel of human/rodent cell hybrids and in a multipoint linkage analysis of 40 CEPH families. These two independent studies both found PLAUR to be located on chromosome 19. The cell hybrid study suggested that PLAUR is located at chromosome 19q13-qter, and the multipoint analysis indicated that PLAUR is located at chromosome 19q13.1-q13.2 and surrounded by DNA markers in the following way (with distances given in recombination fractions): D19S27-.11-CYP2A .06-PLAUR-.03-D19S8-.04-APOC 2-.24-PRKCG. Further, a ligand-binding study performed on cell hybrids verified the species specificity of the uPAR and confirmed the chromosome assignment. PMID- 1311496 TI - Application of transcriptional and posttranscriptional reporter constructs to the analysis of tumor necrosis factor gene regulation. PMID- 1311497 TI - The osteoclast as a unicellular proton-transporting epithelium. AB - Osteoclasts dissolve bone mineral by the vectorial secretion of hydrogen ion at their osseous attachment site. To accomplish this, the osteoclast employs a vacuolar H+ ATPase that is polarized to the specialized proton-secreting plasma membrane domain, the ruffled border. Physiologically and biochemically, they resemble the specialized proton-secreting intercalated cells of the renal collecting duct, which also use a polarized vacuolar H+ ATPase to effect transepithelial hydrogen ion transport. Studies on the mechanism of hydrogen ion transport by the kidney may therefore provide insights into the control of acid secretion by the osteoclast. PMID- 1311498 TI - Focal ventricular thinning caused by indomethacin in the late phase of coxsackievirus B4 murine myocarditis. AB - Indomethacin has been shown to increase virus titers and to worsen cardiac injury in the acute phase of coxsackievirus B4 murine myocarditis. The authors evaluated the effects of indomethacin on the histopathologic changes in a later phase of this disease after virus clearance. Two-day old CD1 mice were infected with coxsackievirus B4. Ten days later, surviving animals were randomized to receive indomethacin or saline intraperitoneally for 10 days. They were then euthanatized, and their hearts were examined for the presence of inflammation, necrosis, scarring, and focal thinning. Mortality was slightly higher among treated animals (7/15 versus 2/12, p = 0.3). The index of inflammation (0.6 +/- 0.5 versus 0.7 +/- 0.5) necrosis and scarring (0.4 +/- 0.5 versus 0.3 +/- 0.5) among treated and control animals, respectively, was not significantly different, but the size of involved myocardium (149742 +/- 201982 versus 35300 +/- 45413 microns2) was remarkably larger (p less than 0.05), and focal ventricular thinning (5/12 versus 0/10, p = 0.03) was encountered among indomethacin recipients exclusively. These findings indicate that indomethacin treatment in the late phase of coxsackievirus B4 myocarditis enhances myocardial damage and increases the incidence of focal ventricular thinning. PMID- 1311499 TI - Hyperoxia induces alkalinization and dome formation in MDCK epithelial cells. AB - We observed that confluent Madin-Darby canine kidney (MDCK) epithelial cells exposed to 95% O2 showed intensive dome formation, a manifestation of cell differentiation and transepithelial fluid transport, whereas cells exposed to 40% O2 or to normoxia did not. Hyperoxia-induced dome formation (HIDF) was preceded and accompanied by a significant rise in intracellular pH (pHi) on days 2 (7.53 vs. 7.42) and 3 (7.62 vs. 7.45), as compared with controls. Inhibition of the Na(+)-H+ exchanger by 0.1 or 1.0 mM amiloride caused 29 or 69% reduction of HIDF and completely abolished hyperoxia-induced alkalinization of the cells. HIDF was altered by modification of extracellular pH (pHo); there was a decrease by 84% with pHo 6.8, while pHo 7.8 led to earlier and more intensive dome formation (day 2, +472%; day 3, +27%). We also found that adenosine 3',5'-cyclic monophosphate (cAMP) was increased in hyperoxic cells, a change that was independent from the rise of pHi. We conclude that high-level hyperoxia induces dome formation in MDCK epithelial monolayers by a process involving activation of the Na(+)-H+ exchanger, together with increased intracellular cAMP. PMID- 1311500 TI - Direct evidence for a basolateral membrane Cl- conductance in toad retinal pigment epithelium. AB - There is now evidence that a Cl- conductance on the basal membrane of the retinal pigment epithelium (RPE) is involved in the generation of both the fast oscillation and the light peak of the direct-current electroretinogram as well as being critical for transepithelial fluid and salt movement. In the present study, we characterized the basolateral membrane Cl- conductance of an in vitro preparation of toad RPE-choroid using conventional and Cl(-)-selective microelectrodes. Under control conditions, the potential across the apical (Vap) and basal (Vba) membranes averaged -60 +/- 2 and -45 +/- 2 mV, respectively (n = 40). Intracellular Cl- activity (aiCl = 20 +/- 1 mM) was distributed above equilibrium across both membranes, consistent with active accumulation of Cl-. A sixfold decrease in Cl- in the basal bath depolarized Vba by 12 +/- 1 mV (n = 17) and increased the apparent basal membrane resistance. By sequential measurement of aiCl and subepithelial Cl- activity during a step decrease in basal Cl-, we constructed the change in Cl- equilibrium potential (ECl) across the basal membrane. Estimation of the change in basal membrane electromotive force during the change in ECl gave an average value for the Cl- transference number (TCl) of 0.45. Further evidence for a Cl- conductance was obtained by measuring changes in aiCl induced by transepithelial current. Depolarizing Vba elevated aiCl, whereas hyperpolarizing Vba had the opposite effect, consistent with conductive Cl- movement across the basal membrane. Both the amplitude of the Cl- diffusion potential and the current-induced changes in aiCl were reduced by basal perfusion with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (250-500 microM), a blocker of Cl- channels in some epithelia. PMID- 1311502 TI - Actions of thiocyanate and N-phenylmaleimide on volume-responsive Na and K transport in dog red cells. AB - Two sets of observations suggest a linkage between volume-responsive Na and K transport systems in dog red blood cells. 1) The lyotropic anion thiocyanate inhibits shrinkage-induced Na-H exchange and stimulates swelling-induced K-Cl cotransport. 2) The effect of a brief incubation with N-phenylmaleimide (NPM) on Na and K transport depends on the volume of the cells at the time of exposure to the sulfhydryl reagent. Cells shrunken during the NPM incubation and then brought back to normal volume behave as though they were still shrunken, i.e., they show an increased Na flux and a decreased K flux. Cells incubated with NPM in a swollen state retain fluxes characteristic of swollen cells when returned to a normal volume. The electrophoretic mobility of the membrane-associated enzyme glyceraldehyde-3-phosphate dehydrogenase is influenced by the cell volume at the time of NPM exposure. These findings point to the existence of a system in cells that perceives volume changes and coordinates the responses of membrane transporters. PMID- 1311501 TI - GTP gamma S-dependent regulation of smooth muscle contractile elements. AB - Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) increases the sensitivity of the contractile response to activation by Ca2+ in permeabilized tracheal smooth muscle. Increased tension was associated with a proportional increase in myosin light chain phosphorylation. The site of phosphorylation was determined to be serine-19, which corresponds to the site rapidly phosphorylated by myosin light chain kinase. GTP gamma S did not affect the contraction induced by the protein phosphatase inhibitor okadaic acid but did enhance contraction produced by Ca(2+) independent myosin light chain kinase. In tracheal homogenates Ca(2+)-dependent myosin light chain kinase activity was not affected by GTP gamma S; however, dephosphorylation of 32P-labeled heavy meromyosin by phosphatase was inhibited. Thus GTP gamma S may increase the Ca2+ sensitivity of contractile elements in tracheal smooth muscle by inhibition of protein phosphatase activity toward myosin light chain. PMID- 1311504 TI - Thyroid hormone induction of rat myocardial Na(+)-K(+)-ATPase: alpha 1-, alpha 2 , and beta 1-mRNA and -protein levels at steady state. AB - In this study, we measured the time courses of change in Na(+)-K(+)-ATPase alpha 1-, alpha 2-, and beta 1-subunit mRNA and protein abundance in cardiac myocytes isolated from euthyroid, hypothyroid, and hyperthyroid (hypothyroids injected daily with 1 microgram T3/g body wt) rats. In hypothyroids, alpha 1-, alpha 2-, and beta 1-protein levels were decreased to 0.55, 0.42, and 0.57 of euthyroids, predicting the decrease in Na(+)-K(+)-ATPase activity to 0.53 of control. There was no change in these subunits' mRNA levels, indicating that the decreases in protein levels were not due to decreased subunit transcription rates. In hyperthyroids, the alpha 1-mRNA increased to a steady state of threefold over hypothyroid by 1 day of T3 treatment, and the alpha 1-protein levels increased to twofold over hypothyroid by 4 days of T3. alpha 2-mRNA increased to 5-fold over hypothyroid by 2 days, whereas the alpha 2-protein levels increased to 14-fold above hypothyroid by 4 days of T3. Beta 1-mRNA increased to 12-fold above hypothyroid by 1 day of T3 treatment, whereas beta 1-protein increased to only 2.5-fold over hypothyroid by 4 days of T3. The discoordinate changes in alpha 2- and beta 1-mRNA vs. protein can be reconciled with the hypothesis that beta 1 is rate limiting for assembly in eu- and hypothyroids, and favors assembly with alpha 1, while excess unassembled alpha 2 is degraded. In the hyperthyroids we predict beta 1 is not rate limiting and there is increased alpha 2 beta 1 assembly. We calculate that T3 decreases the alpha 1-to-alpha 2 ratio from 24:1 in hypothyroid to 3.4:1 in hyperthyroid cardiomyocytes. PMID- 1311503 TI - Synthesis and translocation of Na(+)-K(+)-ATPase alpha- and beta-subunits to plasma membrane in MDCK cells. AB - Synthesis and translocation of Na(+)-K(+)-ATPase alpha-catalytic and beta glycoprotein subunits from intracellular membranes to the plasma membrane were studied in Madin-Darby canine kidney cells (MDCK-T) by combining the methods of pulse-chase labeling, subcellular fractionation on sorbitol gradients, and immunoprecipitation. Immunoprecipitation from homogenates revealed that radioactive methionine incorporated into beta-subunit was equal to that incorporated into alpha-subunit after 15 min of labeling. Because the ratio of total methionines in alpha- vs. beta-subunit is approximately 5:1, these results suggest that beta-subunit is synthesized in molar excess over alpha-subunit. Half of the newly synthesized beta-subunit, likely unassembled units, were degraded by 60 min after labeling, while alpha-subunits were stable through 120 min after synthesis, suggesting alpha may be limiting for alpha beta-assembly. By 120 min the ratio of counts incorporated into alpha vs. beta approached 5, which is predicted by a 1:1 ratio of alpha to beta. The sorbitol gradient resolved two major membrane samples: a mixture of endoplasmic reticulum and Golgi populations and a plasma membrane-enriched sample. Immature beta (beta i) could not be detected in the plasma membrane-enriched samples at levels greater than could be attributed to cross-contamination by intracellular membranes. Mature beta (beta m) became detectable after 30 min, and conversion of beta i to beta m was 90% complete at 120 min. A peak of labeled alpha-subunit appeared in the plasma membrane-enriched sample at 60 min, coincident with the appearance of labeled beta m-subunit in this sample, suggesting movement as alpha beta-heterodimers. PMID- 1311505 TI - Role of G proteins in stimulation of Na-H exchange by cell shrinkage. AB - Many cells respond to shrinkage by stimulating specific ion transport processes (e.g., Na-H exchange). However, it is not known how the cell senses this volume change, nor how this signal is transduced to an ion transporter. We have studied the activation of Na-H exchange in internally dialyzed barnacle muscle fibers, measuring intracellular pH (pHi) with glass microelectrodes. When cells are dialyzed to a pHi of approximately 7.2, Na-H exchange is active only in shrunken cells. We found that the shrinkage-induced stimulation of Na-H exchange, elicited by increasing medium osmolality from 975 to 1,600 mosmol/kgH2O, is inhibited approximately 72% by including in the dialysis fluid 1 mM guanosine 5'-O-(2 thiodiphosphate). The latter is an antagonist of G protein activation. Even in unshrunken cells, Na-H exchange is activated by dialyzing the cell with 1 mM guanosine 5'-O-(3-thiotriphosphate), which causes the prolonged activation of G proteins. Activation of Na-H exchange is also elicited in unshrunken cells by injecting cholera toxin, which activates certain G proteins. Neither exposing cells to 100 nM phorbol 12-myristate 13-acetate nor dialyzing them with a solution containing 20 microM adenosine 3',5'-cyclic monophosphate (cAMP) (or 50 microM dibutyryl cAMP) plus 0.5 mM 3-isobutyl-1-methylxanthine substantially stimulates the exchanger. Thus our data suggest that a G protein plays a key role in the transduction of the shrinkage signal to the Na-H exchanger via a pathway that involves neither protein kinase C nor cAMP. PMID- 1311506 TI - Role of cAMP in mediating effects of fasting on dephosphorylation of insulin receptor. AB - We studied the effect of fasting on phosphotyrosine phosphatase (PTPase) activities in particulate (PF) and cytosolic (CF) fractions of rat adipocytes and liver. PTPase activity was assessed using [32P]tyrosine insulin receptor (IR). In adipocytes, 48 h fasting significantly inhibited PTPase activity. Dephosphorylation of IR by PF and CF PTPases was reduced by 80 and 65%, respectively. Similar reductions of lesser magnitude were observed in fasted rat livers. The effect of fasting was completely reversed by either refeeding or by incubating "fasted" adipocytes for 2 h in tissue culture medium containing 5 mM glucose. Neither 20 mM glucose nor the presence of insulin influenced phosphatase activity. Because fasting is accompanied by elevated protein kinase C (PKC) and adenosine 3',5'-cyclic monophosphate (cAMP) levels, we examined their influence on adipocyte PTPases. Neither activation (1 microM 12-O-tetradecanoylphorbol-13 acetate) nor inhibition (20 microM sphingosine) of PKC affected PTPase activity. In contrast, cAMP (2 mM) significantly inhibited PTPase activity (80% inhibition at 2 h), and its effect was prevented by a cAMP antagonist RpcAMP. Fasting- and cAMP-induced inhibition of PTPase activity was restored by incubating PF with trypsin (4 micrograms/ml for 5 min), which separated the putative inhibitors from the phosphatases. We conclude that fasting-induced inhibition of PTPases is mediated by elevated cAMP levels, most likely by activating phosphatase inhibitors. PMID- 1311507 TI - Insulin receptor kinase activity in muscles and white adipose tissue during course of VMH obesity. AB - Early after lesion of the ventromedial hypothalamus nuclei (VMH), insulin-induced glucose utilization is increased in white adipose tissue (WAT), whereas oxidative and glycolytic muscles are, respectively, normoresponsive or resistant to insulin. Five weeks later, all of the muscles are resistant, whereas WAT returns to normal responsiveness. The aim of this study was to characterize the insulin receptor kinase activity in WAT and muscles 1 and 6 wk after lesion. The number and affinity of insulin receptors were not modified in any of the tissues studied. Autophosphorylation and phosphorylation of an exogenous substrate were similar in oxidative and glycolytic muscles of VMH and control rats both 1 and 6 wk after the lesion. Insulin receptors from WAT of 1-wk VMH rats exhibited a 2.5 fold increase in insulin-stimulated autophosphorylation and phosphorylation. Six weeks after the lesion, both autophosphorylation and phosphorylation returned to normal values. This suggests that insulin receptor tyrosine kinase activity does not play a significant role in the insulin resistance of skeletal muscles but has a crucial role in mediating the variations of insulin action on WAT observed during the development of VMH obesity. PMID- 1311508 TI - Xanthine oxidase and dehydrogenase activities in rat ovarian tissues. AB - The production of reactive oxygen species in the ovary is rapidly inducible, but the nature of the generator is unknown. One possibility is xanthine oxidase (XO), an enzyme that produces superoxide in the presence of hypoxanthine (or xanthine) and oxygen. The objective of the present studies was to measure levels of XO in follicular and luteal tissue to determine whether XO may be a source of reactive oxygen species in the rat ovary. Ovarian levels of XO were about one-fifth of that seen in the liver and adrenal, and XO levels were about one-third of xanthine dehydrogenase (XDH). Preovulatory ovarian levels of XO activity were unchanged after induction of ovulation with gonadotropin and in follicles incubated with gonadotropin. Luteal XO activity was not changed during natural or prostaglandin F2 alpha (PGF2 alpha)-induced luteolysis. Allopurinol, an inhibitor of XO, did not inhibit ovulation or PGF2 alpha-induced luteal regression. Finally, neither catalase and superoxide dismutase nor oxypurinol altered luteal cell function in the presence of hypoxanthine. Thus, while XO is present in the ovary, it does not appear that it is a major source of reactive oxygen species in this organ. PMID- 1311509 TI - Termination of the peripubertal FSH increase in male rats. AB - To determine if the pubertal testosterone rise plays a role in the termination of the peripubertal follicle-stimulating hormone (FSH) increase, male rats were injected with ethylene dimethanesulfonate (EDS) at 40 days of age to eradicate the Leydig cells just before the onset of the testosterone rise. Rats were decapitated at weekly intervals from age 26 to 96 days. Compared with vehicle injected controls, EDS treatment resulted in a delay in the peripubertal increase in the relative weights of prostates and seminal vesicles of approximately 2 wk. Serum testosterone remained at pretreatment levels for 1 wk postinjection. Testicular interstitial fluid testosterone remained at pretreatment concentrations for considerably longer and was significantly lower than controls for 2 wk postinjection. EDS treatment resulted in serum FSH levels that were elevated by 1 wk postinjection. They remained significantly higher than controls until 96 days of age. Compared with controls, serum alpha-inhibin was elevated after EDS as was serum luteinizing hormone. These results suggest that the pubertal testosterone increase plays an important role in terminating the peripubertal FSH rise. PMID- 1311510 TI - Intrinsic factor receptor activity and cobalamin transport in bile duct-ligated rats. AB - The intrinsic factor (IF)-cobalamin (Cbl) receptor activity in the mucosal homogenates progressively decreased after bile duct ligation in the rat, and 80% of the receptor activity was decreased in 96 h after ligation. The activity was restored to normal values of 5.5-6 pmol of IF-[57Co]Cbl bound/g mucosa when the assays were performed with both conjugated and unconjugated bile acids. When [57Co]Cbl bound to intrinsic factor was orally administered, the tissue levels of [57Co]Cbl were decreased by 75-80% in bile duct-ligated rats. The apical membrane receptor activity was also decreased after bile duct ligation; however, the activity was stimulated twofold by the addition of ileal cytosol and threefold with the addition of both ileal cytosol and taurocholate (1 mM). Enhanced binding of IF-[57Co]Cbl to the apical ileal brush-border membrane occurred with the use of dialyzed ileal cytosol but not with cytosol isolated from duodenal or proximal jejunal mucosa. The enhanced binding obtained with ileal cytosol was abolished after its treatment with trypsin. These results suggest that luminal bile acids optimize the binding of IF-Cbl by the ileal membrane receptor via interactions with a cytosolic factor and thus influence the gastrointestinal absorption of cobalamin. PMID- 1311511 TI - Phorbol esters stimulate and inhibit Cl- secretion by different mechanisms in a colonic cell line. AB - Phorbol 12-myristate 13-acetate (PMA) was found to increase both the short circuit current (Isc) and the efflux of 125I- or 36Cl- in the colonic epithelial cell line HT-29.cl19A. Neither the PMA-provoked rise in Isc nor the stimulation of 125I- efflux was affected by the cyclooxygenase inhibitor indomethacin. The PMA-induced increase in Cl- efflux was not accompanied by a rise in adenosine 3',5'-cyclic monophosphate (cAMP) levels. A prolonged incubation with PMA (3 h), however, inhibited the PMA- and the cAMP-stimulated Isc by greater than 90%, whereas the cAMP-provoked 125I- and 36Cl- efflux was not inhibited. The long-term PMA treatment was found to inhibit the basal and cAMP-provoked 86Rb+ efflux by 65 +/- 9 and 86 +/- 7%, respectively. A 3-h incubation with PMA also strongly inhibited the Ca2+ ionophore A23187-induced increase in 86Rb+ efflux, whereas the A23187-stimulated 125I- efflux was only marginally inhibited. These data suggest that phorbol esters, presumably by activation of protein kinase C, can provoke Cl secretion in HT-29.cl19A colonocytes independently of a prostaglandin- or cAMP mediated pathway. Prolonged exposure to PMA, however, causes an inhibition of net electrogenic Cl- secretion by downregulation of the activity of K+ transporters. PMID- 1311512 TI - EndothelinB receptor on guinea pig small intestinal smooth muscle cells. AB - We investigated the binding characteristics of the endothelin (ET) receptor and the mechanism by which ET induces contraction of longitudinal smooth muscle cells of the guinea pig small intestine by using vasoactive intestinal contractor (VIC), a mouse variant of ET-2. A functional receptor for VIC was found to exist on longitudinal smooth muscle cells. These cells showed a similar binding of and contractile response to ET-1, ET-2, and ET-3. Inhibitors of both intracellular and extracellular Ca2+ movement attenuated the VIC-induced contraction of longitudinal smooth muscle cells. These results suggest that smooth muscle cells of the guinea pig small intestine express the ETB receptor that primarily mediates the contractile effect on smooth muscle cells. In addition, ET-induced contraction depends on intracellular as well as extracellular Ca2+. PMID- 1311513 TI - Assessment of signal transduction mechanisms regulating airway smooth muscle contractility. AB - Agonist-receptor interactions regulate airway smooth muscle tone through activation of guanine nucleotide binding proteins (G proteins) which are coupled to second-messenger pathways that mediate changes in the tissue's contractile state. Various methods have been applied to identify the structure/function characteristics of G proteins and their role in signal transduction in airway smooth muscle, including the use of exotoxins, nonhydrolyzable analogs of guanosine-triphosphate (GTP), antibodies to purified G proteins, and membrane reconstitution studies. In elucidating mechanisms of airway smooth muscle relaxation, considerable progress has been made in identifying the molecular basis for receptor/G protein coupling and other regulatory processes leading to both the activation and down-regulation of the adenylate cyclase/adenosine 3',5' cyclic monophosphate system. Further, with respect to airway smooth muscle contraction, various approaches have been used to evaluate the role of membrane phosphoinositide turnover and the mechanisms of action of the bifurcating signal transduction pathways associated with the production and metabolism of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, and activation of protein kinase C. This review identifies much of the information gained to date on the above signal transduction pathways, with an emphasis placed on various methodological approaches used to determine membrane and transmembrane signaling processes in airway smooth muscle. PMID- 1311514 TI - Platelet-derived growth factor and growth-related genes in rat lung. II. Effect of exposure to 85% O2. AB - The expression of platelet-derived growth factor (PDGF), its receptor, and related genes was studied in the lung tissue of rats exposed to air or 85% O2. PDGF-B chain mRNA was increased by 6 days and PDGF B-type receptor mRNA was increased by 4 and 6 days of exposure to 85% O2. Despite a continued increase of cell division, both PDGF-B chain and B-type receptor mRNAs had returned to control values by 14 days of exposure to 85% O2. PDGF-A chain mRNA was unaffected by exposure to 85% O2. Nuclear runoff transcription analysis confirmed increased transcription of PDGF-B chain mRNA, whereas Western blot analysis of lung homogenates suggested consequent increased translation of PDGF-B chain mRNA to PDGF-BB at 7 days of exposure to 85% O2. Combined immunocytochemistry and autoradiography localized PDGF-BB to the major site of cell division, the pulmonary interstitium. We speculate that the early pulmonary fibroblast hyperplasia observed following exposure to 85% O2 is mediated by increased PDGF-B chain gene expression and may also be mediated by changes in PDGF B-type receptor gene expression. PMID- 1311515 TI - Paraquat-induced lung injury: prevention by N-tert-butyl-alpha-phenylnitrone, a free-radical spin-trapping agent. AB - The herbicide paraquat causes lung injury that is believed to be oxygen-radical mediated. To further characterize this injury and explore new methods of preventing it, we used the spin-trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) to identify the paraquat radical in lung tissue and to reduce the injury resulting from the subsequent generation of reactive oxygen species. The formation of a paraquat free radical by guinea pig lung was detected under anaerobic conditions by electron paramagnetic resonance spectrometry. Infused (25, 50, or 100 mg/kg) into guinea pig lungs (perfused at constant flow with Krebs solution containing 4% bovine serum albumin and ventilated with 95% O2-5% CO2), paraquat produced dose-dependent increases in peak airway pressure (Paw), mean pulmonary arterial perfusion pressure (Ppa), and wet-to-dry (W/D) lung weight ratio. At 100 mg/kg, paraquat increased Paw by 589.6 +/- 59.8% (mean +/- SE, n = 8) and W/D ratio from 5.33 +/- 0.07 to 6.29 +/- 0.11 (P less than 0.001). Pulmonary vascular leak index increased from 0.40 +/- 0.09 to 1.96 +/- 0.45 (P less than 0.02), without changes in pulmonary microvascular pressure. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha increased, but indomethacin did not reduce the injury. PBN (2.3 mM) markedly attenuated all evidence of lung injury, which was also reduced by catalase, mannitol, ethanol, and vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311516 TI - Effects of indomethacin on PMA-induced pulmonary endothelial enzyme dysfunction in vivo. AB - We investigated the effects of phorbol myristate acetate (PMA) on metabolic pulmonary endothelial ectoenzyme dysfunction. Anesthetized rabbits were placed on total heart bypass, and the single-pass transpulmonary metabolism of [3H]benzoyl Phe-Ala-Pro (BPAP) by endothelial-bound angiotensin-converting enzyme (ACE) and [14C]adenosine 5'-monophosphate (AMP) by 5'-nucleotidase (NCT) was calculated before and after PMA (10 micrograms/kg iv), a dose that does not produce histologically evident endothelial damage. Under conditions of partial microvascular recruitment (blood flow = 400 ml/min through the entire lung), PMA, but not the vehicle, significantly reduced substrate utilization of both BPAP and adenosine 5'-monophosphate (AMP) and increased the apparent Michaelis constant (Km) values of ACE for BPAP, indicative of metabolic dysfunction. These changes were completely prevented by pretreatment with indomethacin. Under conditions of near full microvascular recruitment (blood flow = 640 ml/min through the left lung only), PMA similarly reduced substrate utilization and increased the apparent Km of ACE for BPAP. In this case, however, indomethacin failed to prevent the observed PMA-induced metabolic dysfunction. We conclude that PMA alters endothelial ectoenzyme substrate metabolism independently from changes in pulmonary blood flow; indomethacin appears to antagonize the effects of PMA under conditions of partial microvascular recruitment only, perhaps by diverting flow to previously unperfused, unexposed to PMA, and hence metabolically healthy vessels. PMID- 1311517 TI - Calcium-dependent regulation of Cl secretion in tracheal epithelium. AB - In primary cultures of dog tracheal epithelium, isoproterenol produced a transient increase in short-circuit current (Isc) (duration 30 s; maximal increase, 32 +/- 5 microA/cm2). This was followed by a more slowly developing sustained increase (9 +/- 3 microA/cm2), which mimicked the response to N6, 2'-O dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). The transient and sustained responses had dissociation constants for isoproterenol of 2 x 10(-8) and 2 x 10(-9) M, respectively. Bradykinin (in the presence of indomethacin), substance P, histamine, and thrombin produced only transient increases in Isc. The time courses of these transients closely paralleled changes in concentration of intracellular Ca ([Ca2+]i) as measured with fura 2. For different mediators, there was a significant correlation between the maximal transient increase in Isc and the maximal increase in [Ca2+]i. The transients in Isc were not associated with elevation of adenosine 3',5'-cyclic monophosphate (cAMP) and were unaffected by pretreatment with DBcAMP, which abolishes the steady-state increase in response to isoproterenol. Both the transient increases in Isc and [Ca2+]i were inhibited by pretreatment with the Ca chelator 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid. The phorbol ester 12-O-tetradecanoylphorbol 13 acetate abolished the transient increases in [Ca2+]i and Isc in response to isoproterenol but not to bradykinin. These results provide evidence that 1) isoproterenol and bradykinin elevate [Ca2+]i by different mechanisms, and 2) Ca elevation is associated with a transient increase in Isc, whereas increased cAMP is associated with a smaller sustained increase. PMID- 1311518 TI - Tracheal epithelial cell fatty acid composition modulates prostaglandin E2 and cAMP production. AB - Tracheal epithelial (TE) cells from both rabbits and humans, when cultured in defined serum-free media without lipid supplements, develop fatty acid profiles significantly different from freshly isolated epithelium, including a markedly decreased cellular content of arachidonic acid (AA). In rabbit TE cells, supplementation of media with a phospholipid-rich lipoprotein extract (Excyte III) plus 1 microM bovine serum albumin-complexed AA (Excyte/AA) restored the fatty acid composition of the cultured cells more similar to that of native airway epithelium than did supplementation of media with 5% fetal bovine serum (FBS). In human TE cells, Excyte/AA or 5% FBS increased AA content, but neither lipid supplement completely "normalized" the fatty acid profiles. Compared with lipid-unsupplemented cultures, basal production of prostaglandin E2 (PGE2) was increased by approximately four- to eightfold in rabbit and human TE cells supplemented with 5% FBS or Excyte/AA. In Excyte/AA-supplemented human TE cells, PGE2 production induced by 5 microM calcium ionophore A23187 was more than threefold greater than that of companion ionophore-stimulated unsupplemented monolayers, but PGE2 production was similar in both culture conditions in response to 10 microM exogenous AA. Thus increased cellular content and availability of AA, rather than changes in cyclooxygenase activity, appear to be responsible for the elevated PGE2 production in Excyte/AA-supplemented human TE cells. Secondary effects of lipid supplementation were also observed; Excyte/AA supplemented human TE cells produced significantly less adenosine 3',5'-cyclic monophosphate (cAMP) in response to exogenous PGE2 and isoproterenol than did lipid-unsupplemented cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311519 TI - Endothelin regulation of mucus glycoprotein secretion from feline tracheal submucosal glands. AB - We examined the effects of endothelin on both the trichloroacetic acid precipitable 3H-labeled glycoconjugate release and intracellular Ca2+ concentration ([Ca2+]i]) measured by the usage of fura-2 in submucosal glands isolated from feline trachea. Endothelin-1 produced a significant increase in glycoconjugate release from the isolated glands in a dose-dependent fashion, reaching a response of 161% of the control at 10(-6) M. Atropine, propranolol, phentolamine, or indomethacin did not produce any significant alterations in the ET-1-evoked glycoconjugate secretion from the isolated glands. In contrast, in tracheal explants which contained epithelium, ET-1 produced a significant reduction in the glycoconjugate secretion in a dose-dependent fashion, reaching a response of 59% of the control at 10(-6) M. In the presence of cultured epithelial cells, ET-1 also produced a significant reduction in the glycoconjugate secretion from isolated glands. In isolated glands, ET-1 produced a sustained increase in the [Ca2+]i which was abolished by the removal of Ca2+ from the medium or by the presence of cultured epithelial cells. Pretreatment with indomethacin failed to alter the epithelial inhibitory action evoked by ET-1 in both the glycoconjugate secretion and the [Ca2+]i in isolated glands. ET-2 and ET-3 failed to produce significant alterations in the glycoconjugate secretion or [Ca2+]i. These findings indicate 1) that ET-1 induces mucus glycoprotein secretion via a Ca2+ influx and 2) that it possibly augments the an epithelial action inhibitory to the mucus glycoprotein secretion from airway submucosal glands. PMID- 1311520 TI - Effect of pharmacological manipulation of endogenous atriopeptin activity on renal function. AB - Atrial stretch causes the release of atriopeptin (AP, ANF) from preformed vesicular storage sites. The circulating hormone acts on unique receptor sites (containing guanylate cyclase) to release guanosine 3',5'-cyclic monophosphate (cGMP) that mediates the natriuresis and vasodilation and probably the suppression of renin, aldosterone, and vasopressin. The biological effects of atriopeptin are transient because of the rapid inactivation of the circulating hormone (by neutral endopeptidase or clearance receptors) or the second messenger (by cGMP-phosphodiesterase). Heart failure due to chronic cardiac volume overload [aortovenocaval (A-V) fistula] exhibits markedly elevated circulating AP blood levels and urinary cGMP levels, accompanied by induction of ventricular AP gene and protein expression and release. Pharmacological manipulation of endogenous AP, either by inhibiting cGMP phosphodiesterase (i.e., mediator prolongation) or neutral endopeptidase (i.e., prolongation of hormone half-life) in A-V fistula animals results in profound natriuresis and diuresis without hypotension. These pharmacological maneuvers bypass the suppressed renal response to exogenous AP seen in heart failure and provide a rational therapeutic strategy based on our understanding of the underlying physiological and pathological mechanisms. PMID- 1311521 TI - Mechanism of decreased calcitriol degradation in renal failure. AB - Metabolic clearance rate (MCR) of calcitriol is decreased in renal failure, and uremic toxins play a major role in the suppression of calcitriol degradation. In this experiment, we studied the effect of uremic toxins on renal 24- and 26 hydroxylase (HX) activities. Normal rats were infused for 20 h with 30 ml of normal or uremic plasma ultrafiltrates. At the end of infusion, renal enzymes activities were measured by the generations of 1,24,25- and 1,25,26 trihydroxyvitamin D3 10 min after the addition of 25 nM or 1 microM calcitriol. Renal 24-HX activity decreased approximately 50%, whereas 26-HX activity did not decrease in rats infused with uremic plasma ultrafiltrate. The induction of 24-HX activity by 100 ng calcitriol also decreased in rats infused with uremic ultrafiltrate. To examine whether uremic ultrafiltrate could directly inhibit the degradation enzymes, 24- and 26-HX activities were measured in kidney homogenates preincubated for 3 h with either normal or uremic ultrafiltrate. Uremic ultrafiltrate did not directly suppress 24- and 26-HX activities. Furthermore, the disappearance rate of calcitriol was similar for 90 min in kidney homogenates after they were preincubated for 3 h with uremic and normal ultrafiltrates. Because 24-HX synthesis is induced by the calcitriol-receptor complex binding to nuclear chromatin and activating genes coding for the enzyme, we studied the effect of uremic toxins on the binding affinity of calcitriol-receptor complex for DNA-cellulose. Uremic ultrafiltrate significantly reduced the binding affinity of the hormone receptor complex for DNA when the receptor was preincubated with the ultrafiltrate for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311522 TI - Parathyroid hormone inhibits proximal tubule Na(+)-K(+)-ATPase activity. AB - Parathyroid hormone (PTH) decreases the transepithelial transport of Na+ in the proximal tubule, an action ascribed to PTH-inhibited apical Na(+)-H+ exchanger dependent Na+ entry. We tested the possibility that PTH could also diminish Na(+) K(+)-ATPase-dependent Na+ exit. To dissociate effects on Na+ entry, studies were performed in a suspension of rat proximal tubules by measuring nystatin stimulated ouabain-inhibitable O2 consumption (QO2) and monensin-stimulated ouabain-sensitive 86Rb uptake in the absence or presence of bovine PTH-(1-34) fragment. PTH inhibited the percent nystatin-stimulated QO2 in a concentration dependent manner, with maximal effect at 10(-10) M. PTH-increased cAMP formation was seen at doses higher than 10(-9) M and was maximal at 10(-7) M. Dibutyryl cAMP (10(-4) M) only partially reproduced the PTH action on QO2. Angiotensin II (10(-6) M) blunted the effect of 10(-7) M PTH on QO2, although it did not change 10(-7) M PTH-dependent cAMP generation. The analogues PTH-(3-34) and [Nle8,Nle18,Tyr34]PTH-(3-34)-amide mimicked the effects of PTH-(1-34) on QO2 but did not affect cAMP formation. Monensin-stimulated ouabain-sensitive 86Rb uptake was inhibited by PTH in a dose-dependent manner, with 10(-7) M PTH being maximally inhibitory. Na(+)-K(+)-ATPase activity was also decreased by PTH-(3-34) in a concentration-dependent manner, with maximal effect occurring at 10(-8) M. Agonist-dependent inhibition of Na+ pump was not due to a decrease of mitochondrial activity, because mitochondrial uncoupled QO2 rates were the same in control and PTH-treated tubules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311523 TI - Localization of ecto-ATPase in rat kidney and isolated renal cortical membrane vesicles. AB - Brush-border (BBMV) and basolateral membrane vesicles (BLMV) from rat renal cortex exhibit an ecto-ATPase activity that is distinct from other ATPases. We have examined the cellular and regional distribution of this enzyme in rat kidney using antibodies against rat liver ecto-ATPase. In isolated vesicles, the distribution shown by biochemical assays of ATPase activity was confirmed by immunocytochemistry and Western blotting. Indirect immunofluorescence and immunogold labeling showed that brush borders of the S1 and S3 segments of the proximal tubule (PT) were stained, but the S2 segment was negative. Staining was most intense in the S3 segment. The luminal membrane of the initial part of the thin descending limb of Henle also showed a marked staining. Surprisingly, basolateral plasma membranes of PT had no detectable staining. However, the plasma membrane of endothelial cells was heavily stained, both in larger vessels and in peritubular capillaries. Using an antibody against rat thrombomodulin, a marker for endothelial cell plasma membranes, we showed that preparations of BBMV, BLMV, and endocytic vesicles are all contaminated with these membranes. This may explain, at least partially, the biochemically measured ecto-ATPase activity in renal cortical membrane vesicles. Finally, no specific staining in the kidney was found using polyclonal antipeptide antibodies against the "long form" of liver ecto-ATPase, either by immunocytochemistry or by Western blotting. This indicates either that there is no long isoform of the ecto-ATPase in the kidney or that the intracellular domains of the long form are different in the two tissues. PMID- 1311524 TI - PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct. AB - To assess sites and mechanism of action of prostaglandin E2 (PGE2) on water permeability (PF), we determined PGE2 effects on antidiuretic hormone (ADH)- and adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated PF in rat terminal inner medullary collecting ducts perfused in vitro. PGE2 (10(-7) M) reversibly inhibited ADH-stimulated PF (1.131 +/- 192 to 532 +/- 208 microns/s). In contrast to that observed in rabbit, PGE2 also inhibited an established PF response to the exogenous cAMP analogue 8-p-(chlorophenylthio)-cAMP (696 +/- 107 to 399 +/- 99 microns/s). PGE2 alone had no effect on PF. The protein kinase C inhibitor staurosporine (10(-8) M) blocked PGE2-mediated inhibition of cAMP-stimulated PF. PGE2 caused a rapid spikelike increase in intracellular calcium [( Ca2+]i) followed by a stable elevation above basal values. Only the latter effect was abolished in a zero calcium bath. Neither staurosporine nor cAMP altered the [Ca2+]i response. These studies are the first to demonstrate PGE2-mediated inhibition of an established PF response to cAMP independent of changes in intracellular cAMP. The pattern of [Ca2+]i release and sensitivity to staurosporine suggests that this effect is mediated via signaling through phospholipase C. The results underscore the importance of species differences, axial heterogeneity, and/or in vivo conditioning for functional expression of cellular signaling pathways. PMID- 1311525 TI - Vasopressin regulates apical and basolateral Na(+)-H+ antiporters in mouse medullary thick ascending limbs. AB - We assessed in isolated perfused mouse medullary thick ascending limb (MTAL) segments Na(+)-H+ antiporter activity in both apical and basolateral membranes and the effects of arginine vasopressin (AVP) on the activities of these antiporters under isotonic conditions using 2',7'-bis(carboxyethyl)-5(6) carboxyfluorescein to monitor intracellular pH (pHi). When the apical Na(+)-H+ antiporter was inhibited in the absence of AVP with removal of luminal Na+ plus addition of 0.5 mM amiloride, a small but significant increase in pHi was observed after luminal NH4Cl-induced acidification of MTAL cells to pHi less than 6.7. This increase in pHi was dependent on basolateral Na+ and inhibited with 0.5 mM basolateral amiloride, consistent with the function of a basolateral Na(+)-H+ antiporter. Basolateral AVP (100 microU/ml) enhanced the rate of pHi recovery due to the basolateral Na(+)-H+ antiporter by more than twofold. In contrast, AVP decreased the apical Na(+)-H+ antiporter activity by 50%. In the absence of AVP, addition of 0.5 mM amiloride to the luminal perfusate reduced steady-state pHi by 0.40 +/- 0.07 units, whereas exposure of the basolateral membrane to the same concentration of amiloride had no effect on pHi (delta pHi = 0.01 +/- 0.01 units). AVP reduced the magnitude of cell acidification on exposure of apical membranes to amiloride (delta pHi = 0.16 +/- 0.03) but increased the pHi response to basolateral amiloride (delta pHi = 0.09 +/- 0.00). Thus Na(+)-H+ antiporters are present on both apical and basolateral membranes of the mouse MTAL in the absence of AVP. AVP stimulates the basolateral, while inhibiting the apical, Na(+)-H+ antiporter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311526 TI - Cholinergic stimulation of phosphoinositide metabolism in isolated rat glomeruli. AB - Cholinergic effects on kidney function have been observed in some mammals but the intrarenal localization and the cellular mechanisms of these effects are poorly defined to date. The aim of this work was to study the effects of carbachol on phosphoinositide metabolism in freshly isolated rat glomeruli labeled with myo [3H]inositol. Carbachol rapidly and markedly stimulates phosphoinositide metabolism with a 50% effective concentration of 3 microM. The enormous magnitude of the response is enlightened by the use of 10 mM lithium, which provokes in the presence of the agonist a large accumulation of inositol phosphates and a corresponding depletion of cellular free inositol. The response is inhibited by 85% by pirenzepine, is pertussis toxin insensitive, and shows no desensitization at maximum dose of carbachol up to 40 min of stimulation. PMID- 1311527 TI - Permeation of divalent cations through the Ca2+ channel of rabbit portal vein myocytes. AB - The divalent selectivity of the Ca2+ channel in the rabbit portal vein myocyte was examined by the whole cell clamp method. A concentration-dependent selectivity of divalent ion permeation was found such that when Ca2+ was replaced by Ba2+ or Sr2+, the order of maximum current was Ca2+ = Ba2+ greater than Sr2+ at 2 mM and Ba2+ greater than Sr2+ greater than or equal to Ca2+ at 5-10 mM. The possibility of block of the Ca2+ channel by micromolar concentrations of "contaminant" Ca2+ as a determinant of change in the order of selectivity of divalents was examined. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' tetraacetic acid (500 microM) significantly increased maximum Ba2+ current (IBa) or ISr in solution containing 5 mM Ba2+ or Sr2+. Furthermore, at 5 mM extracellular Ba2+ concentration, addition of 10, 20, 50, and 100 microM Ca2+ caused a 6, 14, 22, and 33% decrease in IBa, respectively. These results suggest that the portal vein Ca2+ channel has three orders of magnitude higher selectivity for Ca2+ over Ba2+ and Sr2+ such that micromolar Ca2+ may block permeation of other divalents through the channel. PMID- 1311528 TI - Oxygen modulates endothelium-derived relaxing factor production in fetal pulmonary arteries. AB - Alterations in endothelium-derived relaxing factor (EDRF) production or mechanism of action may be involved in the responses of the developing pulmonary vasculature to changes in oxygenation. In this study the effects of acute changes in in vitro oxygen tension on EDRF production were determined in isolated segments of ovine fetal intrapulmonary arteries (4th generation) obtained at 125 135 days of gestation (term 144 +/- 4 days). EDRF production was assessed by measuring segment guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the presence of a phosphodiesterase inhibitor. Basal (nonstimulated) cGMP production and cGMP production with acetylcholine (ACh) stimulation were dependent on the presence of the endothelium, on the availability of L-arginine, and on soluble guanylate cyclase activity, confirming that they were indicative of EDRF production. cGMP production with sodium nitroprusside (SNP) was used to discriminate changes in the sensitivity of soluble guanylate cyclase with varying conditions. With decreasing oxygen tension, basal and ACh-stimulated cGMP production were attenuated, whereas cGMP production with SNP was not, indicating oxygen modulation of EDRF production. Studies of endothelium-dependent relaxation yielded comparable findings in that the response to ACh was attenuated, but that to SNP was not altered by decreased oxygenation. In addition, the decline in endothelium-dependent relaxation with decreased oxygen tension was rapidly reversed when oxygenation was increased. Parallel experiments examining cGMP production in similarly sized mesenteric arteries revealed that the effect of oxygen on pulmonary artery EDRF production may be specific to that vascular bed. These findings indicate that oxygen selectively modulates EDRF production and endothelium-dependent relaxation in ovine fetal pulmonary arteries. Direct effects of oxygen on EDRF production may at least partially underlie the responses of the developing pulmonary circulation to changes in oxygenation. PMID- 1311529 TI - Polyunsaturated fatty acids in cultured cardiomyocytes: effect on physiology and beta-adrenoceptor function. AB - This study was carried out to investigate the influence of the membrane fatty acid composition on the basal electrical and contractile activities and the response to beta-adrenergic stimulation of rat cardiac muscle cells in culture. Cells were grown for 3 days in a conventional serum culture medium and then incubated for 24 h in synthetic media containing either n-6 or n-3 as the sole source of polyunsaturated fatty acids (PUFA). The n-6/n-3 ratio in the phospholipids was 0.9 in the n-3 cells and 13.1 in the n-6 cells compared with 6.3 in controls cells. Such modifications did not alter action potentials and the main parameters related to contraction, although shortening was slightly accelerated in the n-6 cells. On the other hand, the positive chronotropic effect induced by isoproterenol was more pronounced (P less than 0.01) in n-3 cells than in n-6 cells. In addition, isoproterenol caused a decrease in contraction duration and in shortening and relaxation time that was less pronounced in n-6 than in control cells (P less than 0.01, P less than 0.01 and P less than 0.05, respectively). These results suggest that the PUFA balance in the phospholipids may contribute to modulate the cardiac adrenergic receptor system but not the membrane properties related to electro-mechanical functions. PMID- 1311530 TI - Role of cAMP-dependent protein kinase in cAMP-mediated vasodilation. AB - In this study, the role of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) in cAMP-dependent relaxation was assessed in the isolated perfused rat lung using a PKA inhibitor, Rp-cAMPS, 8-bromo-cAMP (8-BrcAMP), and the diterpene activator of adenylate cyclase (AC), forskolin (FSK). A role for K+ channels was also assessed with the nonselective K+ channel blocker, tetraethylammonium (TEA, 10 mM), and an ATP-sensitive K+ channel inhibitor, glibenclamide (GLI, 100 microM). Both 8-BrcAMP (0.1-1.0 mM) and RSK (0.1-10 microM) dose-dependently attenuated the peak pressor response to alveolar hypoxia (HPR). Rp-cAMPS potentiated the HPR and attenuated 8-BrcAMP-mediated vasodilation but had no effect on FSK-mediated vasodilation. FSK-mediated vasodilation was not mimicked by 1,9-dideoxy-FSK, which is biologically inactive on AC but alters K+ channels identically to FSK, nor was it attenuated by the platelet-activating factor antagonist SRI 63-441 or the cyclooxygenase inhibitor indomethacin. TEA, but not GLI, attenuated FSK-mediated vasodilation. Similarly, TEA attenuated 8 BrcAMP-mediated vasodilation. These results support roles for PKA and indirect gating of a non-ATP-sensitive K+ channel in mediating cAMP-dependent pulmonary vasodilation. PMID- 1311532 TI - Bowditch Lecture. Renal afferent inputs to ascending spinal pathways. AB - Studies of renal afferent fibers and their functions have continued since the work of Pines in 1959 (Fiziol. Zh. SSSR Im. I M Sechenova 45: 1339-1347, 1959). The kidney contains mechanoreceptors and chemoreceptors that appear to have two major functions. First, renal mechano- and chemoreceptors evoke a variety of renorenal reflexes, while more global cardiovascular reflexes are primarily evoked by renal mechanoreceptors. A second function of renal afferent fibers is to cause the pain of renal disease. Recent studies suggest that renal afferent fibers may also regulate secretion of vasopressin from the pituitary gland. Substantial evidence indicates that, although most renal afferent fibers enter the spinal cord, their functions depend to a large extent on supraspinal circuitry. Thus our research has focused on defining characteristics of spinal neurons that relay renal information to the brain. In the cat, neurons in the L2 T11 segments with excitatory responses to renal A delta and C fiber input project to the medial medullary reticular formation and to the caudal and rostral ventrolateral medulla. Renal afferent information reaches these cells by way of the least splanchnic nerve and by way of more than one dorsal root. In the monkey spinothalamic neurons in the L3-T10 segments respond to renal nerve stimulation. Excitatory responses predominate, but inhibitory responses occur in L2 and L3. These cells also respond to renal A delta and C fibers. Stimulation of renal mechanoreceptors by occlusion of the ureteropelvic junction or renal vein excites feline spinoreticular neurons. Graded increases in renal vein pressure produce graded increases in cell responses. Activation of renal chemoreceptors increases activity of spinal interneurons. Within the L2-T11 segments, cells responding to ureteral occlusion are located caudally, cells with responses to renal artery occlusion are located rostrally, and cells responding to renal vein occlusion are located in between. The differential locations of cells with these inputs suggests the existence of a coding mechanism for different renal receptor populations. Distention of the renal pelvis is a potent stimulator of primate spinothalamic neurons. These neurons encode renal pelvic pressures in the noxious range and appear to be important in mechanisms of renal pain. PMID- 1311531 TI - C-myc protooncogene modulates cardiac hypertrophic growth in transgenic mice. AB - Protooncogenes such as c-myc have been implicated in the transduction of growth signals in the cardiac myocyte. We examined whether increases in c-myc expression occur in murine heart in vivo as a generalized response to the pharmacological stimulation of myocyte growth. Both triiodothyronine (T3) and the beta-adrenergic agonist isoproterenol were demonstrated to induce a rapid and transient increase in cardiac c-myc mRNA abundance, which preceded an increase in cardiac mass. We then examined whether myocyte growth could be modulated by selectively altering cardiac c-myc expression. The model system used was a strain of transgenic mice exhibiting a 20-fold increase in cardiac c-myc expression. Although in nontransgenic mice the administration of T3 and isoproterenol resulted in similar increases in cardiac mass, in transgenic mice the degree of myocardial growth induced with T3 was significantly greater than that induced with isoproterenol (P less than 0.001). This study demonstrates that increasing the basal expression of c-myc in cardiac myocytes alters the growth response of the heart in vivo to certain hypertrophic stimuli and implicates the c-myc protooncogene in the transduction of selective hypertrophic growth signals in differentiated cardiac myocytes. PMID- 1311533 TI - Modulation of plasma aldosterone by physiological changes in hydrogen ion concentration. AB - To assess the effect of extracellular hydrogen ion concentration (PH+) on aldosterone secretion, studies in which other known modulators could be controlled were performed on 13 patients undergoing hemodialysis. High (35 mM) or low (14-17 mM) dialysate bicarbonate concentrations were utilized on separate days to either decrease or increase PH+, while plasma potassium concentrations (PK) were held at constant levels and changes in plasma renin activity (PRA) were minimized by avoiding changes in body weight. Changes in PH+ were associated with concordant changes in plasma aldosterone concentration (Pa) in both high- and low bicarbonate studies. When these changes in Pa in high- and low-bicarbonate studies were analyzed together as a function of corresponding changes in PH+, a significant correlation could be demonstrated (r = 0.659, P less than 0.001). There was no correlation between changes in Pa and changes in PK, plasma sodium, plasma adrenocorticotropic hormone (ACTH), or PRA. Using the same methods to control PH+ and other variables during hemodialysis, the effects of altered PH+ on ACTH-stimulated aldosterone and cortisol secretion were evaluated in studies on six patients who received incremental infusions of ACTH after pretreatment with dexamethasone. In these studies, there was no demonstrable effect of PH+ on Pa or plasma cortisol concentration. We conclude that physiological changes in PH+ have a weak modulating effect on basal aldosterone secretion that may not be evident in the presence of other acutely applied stimuli. PMID- 1311534 TI - Ultrastructural aspects of replication of the New Jersey serotype of vesicular stomatitis virus in a suspected sand fly vector, Lutzomyia shannoni (Diptera: Psychodidae). AB - Transmission electron microscopy was used to examine replication of the New Jersey serotype of vesicular stomatitis virus (VSNJ) (Rhabdoviridae: Vesiculovirus) in Lutzomyia shannoni (Diptera: Psychodidae), a recently implicated sand fly vector. Following ingestion of an infectious blood meal, female sand flies were fixed and examined at approximately 12-hr intervals for six days. The New Jersey serotype of vesicular stomatitis virus was first detected in the abdominal midgut after 34 hr of incubation. Virus next appeared in fat body and the thoracic midgut at 48 hr, while salivary glands first contained visible virus in apical cavities 5-6 days after infection. Flight muscles and nervous tissue occasionally contained small numbers of VSNJ virions, while virus was never detected in the ovaries or malphigian tubules. The midgut and fat body appeared to be major sites of VSNJ virus replication. In all tissues examined, virus matured primarily by budding from the plasma membrane. Virions were occasionally observed within vacuoles, along with nucleocapsids. In the midgut, budding occurred exclusively from the basolateral plasma membrane, while maturation in salivary gland cells involved apical budding. Accumulation of virions adjacent to basal laminae surrounding several tissues suggested that this structure physically impedes virus dissemination within the sandfly. The paucity of virus budding 120-144 hr after infection suggested that the VSNJ virus infection was modulated in Lu. shannoni. PMID- 1311535 TI - Mivacurium: dose-response relationship and administration by repeated injection or infusion. AB - The dose-response relationship and neuromuscular blockade after infusion or repeated injection of mivacurium were studied in 65 patients in nitrous oxide narcotic anesthesia. The ED95 (twitch tension) was determined in 45 patients by intravenous injection of a single bolus of 30, 39, 47, 54, or 60 micrograms/kg (9 patients per dose). Another 20 patients received an initial bolus of 2 x ED95 followed either by an infusion started at 5% twitch recovery (i.e., 95% depression) and adjusted to sustain 95% twitch depression (n = 10) or by repeated injection of 0.6 x ED95 whenever twitch tension had recovered to 25% of control (n = 10). Five patients in each of these two groups received 7 micrograms/kg of neostigmine at 25% twitch recovery, and the others recovered twitch tension spontaneously. The mean ED95 was 73 micrograms/kg. A 2 x ED95 bolus was followed by complete twitch depression within 2.2 +/- 0.7 min. The mean infusion rate resulted in 6 +/- 2 micrograms.kg-1.min-1. The ensuing recovery index was 6 +/- 3 min. A 6 +/- 2 min recovery index was found after up to 10 repeat injections given every 9 +/- 3 min. There was no significant effect of neostigmine in both groups. In conclusion, the recovery indices after the infusion or repeat injection of near-equal doses of mivacurium were identical. PMID- 1311536 TI - Epidural anesthesia in patients with Klippel-Trenaunay syndrome. PMID- 1311537 TI - Clinical and pathologic effects of oral administration of transmissible gastroenteritis vaccine to gnotobiotic pigs. AB - Pigs from 3 litters kept under gnotobiotic conditions were inoculated orally with virulent transmissible gastroenteritis (TGE) virus, a TGE vaccine, or Hank's balanced salt solution at 2 days of age and then euthanatized at intervals ranging from 1 to 7 days after inoculation. Pigs exposed to the vaccine had clinical evidence of diarrhea and weakness. Lesions resembling those of TGE were revealed grossly, microscopically, and by scanning electron microscopy. Viral antigen was seen in intestinal epithelial cells by the direct fluorescent antibody technique. The disease induced by the vaccine virus had a longer incubation period and lesions were less severe than that induced by the virulent virus. PMID- 1311538 TI - Transplacental infection of porcine fetuses following experimental challenge inoculation with encephalomyocarditis virus. AB - Ten multiparous sows were inoculated between 46 and 50 days of gestation with a fetal swine isolate of encephalomyocarditis virus (EMCV) to investigate the ability of the virus to cause transplacental infection and fetal death. Four sows (group 1) were inoculated IM with EMCV MN-25 that had been passaged 4 times on baby hamster kidney-21 line cell monolayers. Two sows were euthanatized at postinoculation (PI) day 23, and the other 2 sows at PI day 44. An additional 6 sows (group 2) were inoculated IM with the same virus that had been passaged 5 additional times in pigs. Two sows were euthanatized at 14 days, and the remaining 4 sows at PI day 28. Clinical signs were not observed in any of the sows, whereas all sows seroconverted to EMCV. In group 1, only 2 of 50 fetuses were mummified. Virus was not recovered, although EMCV antibodies were detected in the 2 mummified fetuses. In group 2, the 2 sows that were euthanatized at PI day 14 had 26 normal fetuses and there was no evidence of fetal infection. However, in the 4 sows euthanatized at PI day 28, 20 of 48 fetuses were mummified, hemorrhagic, or edematous. Encephalomyocarditis virus was recovered from 21 of 48 fetuses. Transplacental infection and fetal deaths in pregnant sows was achieved following infection with EMCV passaged in pigs. PMID- 1311539 TI - Evaluation of colostral IgG1 absorption in newborn calves after treatment with alkalinizing agents. AB - The effects of alkalinizing agents, administered prior to feeding colostrum, on blood-gas and acid-base values and on absorption of IgG1 were determined in 40 newborn Holstein calves. Two treatments, sodium bicarbonate (3 mEq/kg of body weight, IV) and doxapram HCl (2 mg/kg, IV), were evaluated, using a randomized complete-block experimental design. These treatments resulted in significant (P less than 0.01) alteration of blood-gas and acid-base values, generally in the direction of normal values for adult cattle. Significant least squares mean effects were detected for sodium bicarbonate treatment on blood pH (+ 0.04 units, P less than 0.01), PCO2 (+ 4.1 mm of Hg, P less than 0.01), and HCO3 concentration (+ 4.4 mEq/L, P less than 0.01). Significant least squares mean effects were detected for doxapram HCl treatment on blood pH (+ 0.06 pH units, P less than 0.01) and PCO2 (-5.2 mm of Hg, P less than 0.01). Absorption of colostral IgG1 was not affected by the treatments given or by the altered blood gas and/or acid-base status. PMID- 1311540 TI - Accumulation of yolk proteins in insect oocytes. PMID- 1311541 TI - The mode of action of Bacillus thuringiensis endotoxins. PMID- 1311542 TI - Use of bioluminescence for detection of genetically engineered microorganisms released into the environment. AB - The persistence and movement of strain JS414 of Xanthomonas campestris pv. campestris, which was genetically engineered to bioluminesce, were monitored during a limited field introduction. Bioluminescence and traditional dilution plate counts were determined. Strain JS414 was applied to cabbage plants and surrounding soil by mist inoculation, by wound inoculation, by scattering infested debris among plants, and by incorporating bacteria into the soil. Bioluminescent X. campestris pv. campestris was detected in plant samples and in the rhizosphere up to 6 weeks after inoculation. Movement to uninoculated plants was detected on one occasion, but movement from the immediate release area was not detected. Strain JS414 was detected in soil samples beneath mist- and wound inoculated plants only at intentionally infested locations and in aerial samples only on the day of inoculation. Our bioluminescence methods proved to be as sensitive as plating methods for detecting the genetically engineered microorganisms in environmental samples. Our results demonstrate that transgenic incorporation of the luxCDABE operon provides a non-labor-intensive, sensitive detection method for monitoring genetically engineered microorganisms in nature. PMID- 1311543 TI - Involvement of a chlorobenzoate-catabolic transposon, Tn5271, in community adaptation to chlorobiphenyl, chloroaniline, and 2,4-dichlorophenoxyacetic acid in a freshwater ecosystem. AB - A chlorobenzoate-catabolic transposon (Tn5271) was introduced on a conjugative plasmid (pBRC60) in the natural host, Alcaligenes sp. strain BR60, into lake water and sediment flowthrough microcosms. Experimental microcosms were exposed to micromolar levels of 3-chlorobenzoate, 4-chloroaniline, 2,4 dichlorophenoxyacetate, or 3-chlorobiphenyl. The populations of the host, BR60, and organisms carrying Tn5271 were monitored over a 100-day period by use of selective plate counts and the most-probable-number-DNA hybridization method. Populations of Tn5271-carrying bacteria were significantly higher in microcosms dosed with 3-chlorobenzoate, 4-chloroaniline, and 3-chlorobiphenyl than in the control microcosms, indicating that each of these chemicals exerts a selective force on this particular genotype in natural systems. The rates of 3 chlorobenzoate uptake and respiration correlated with Tn5271-carrying populations, as did the rates of 4-chloroaniline uptake and respiration. Plasmid transfer in the 3-chlorobenzoate- and 3-chlorobiphenyl-dosed microcosms resulted in the selection of three phenotypic clusters of chlorobenzoate degraders, only one of which was closely related to the original pBRC60 (Tn5271) donor, Alcaligenes sp. strain BR60. Bacteria dominating 4-chloroaniline-dosed microcosms carried IS1071, the class II insertion sequence that brackets Tn5271, on a plasmid unrelated to pBRC60. The importance of plasmid transfer and transposition during chemical adaptation is discussed. PMID- 1311544 TI - Cloning and nucleotide sequence of the gene coding for citrate synthase from a thermotolerant Bacillus sp. AB - The structural gene coding for citrate synthase from the gram-positive soil isolate Bacillus sp. strain C4 (ATCC 55182) capable of secreting acetic acid at pH 5.0 to 7.0 in the presence of dolime has been cloned from a genomic library by complementation of an Escherichia coli auxotrophic mutant lacking citrate synthase. The nucleotide sequence of the entire 3.1-kb HindIII fragment has been determined, and one major open reading frame was found coding for citrate synthase (ctsA). Citrate synthase from Bacillus sp. strain C4 was found to be a dimer (Mr, 84,500) with a subunit with an Mr of 42,000. The N-terminal sequence was found to be identical with that predicted from the gene sequence. The kinetics were best fit to a bisubstrate enzyme with an ordered mechanism. Bacillus sp. strain C4 citrate synthase was not activated by potassium chloride and was not inhibited by NADH, ATP, ADP, or AMP at levels up to 1 mM. The predicted amino acid sequence was compared with that of the E. coli, Acinetobacter anitratum, Pseudomonas aeruginosa, Rickettsia prowazekii, porcine heart, and Saccharomyces cerevisiae cytoplasmic and mitochondrial enzymes. PMID- 1311546 TI - Development of plasmid cloning vectors for Thermus thermophilus HB8: expression of a heterologous, plasmid-borne kanamycin nucleotidyltransferase gene. AB - While several Thermus genes have been cloned and T. thermophilus has been shown to be transformable, molecular genetic studies of these thermophiles have been hampered by the absence of selectable cloning vectors. We have constructed a selectable plasmid by random insertion of a heterologous gene encoding a thermostable kanamycin nucleotidyltransferase activity into a cryptic, multicopy plasmid from T. thermophilus HB8. This plasmid should serve as a suitable starting point for the development of a gene expression system for T. thermophilus. PMID- 1311545 TI - Characterization of lactoferrin binding by Aeromonas hydrophila. AB - Various lactoferrin preparations (iron-saturated and iron-depleted human milk lactoferrins and bovine milk and colostrum lactoferrins) were bound by Aeromonas hydrophila. Binding was (i) reversible (65% of bound lactoferrin was displaced by unlabeled lactoferrin), (ii) specific (lactoferrin but not other iron-containing glycoproteins such as ferritin, transferrin, hemoglobin, and myoglobin inhibited binding), and (iii) significantly reduced by pepsin and neuraminidase treatment of the bacteria. The glycosidic domains of the lactoferrin molecule seem to be involved in binding since precursor monosaccharides of the lactoferrin oligosaccharides (mannose, fucose, and galactose) and glycoproteins which have homologous glycosidic moieties similar to those of the lactoferrin oligosaccharides (asialofetuin or fetuin) strongly inhibited lactoferrin binding. A. hydrophila also binds transferrin, ferritin, cytochrome c, hemin, and Congo red. However, binding of these iron-containing compounds seems to involve bacterial surface components different from those required for lactoferrin binding. Expression of lactoferrin binding by A. hydrophila was influenced by culture conditions. In addition, there was an inverse relationship between lactoferrin binding and siderophore production by the bacterium. PMID- 1311547 TI - Slow viruses and the immune system in the pathogenesis of local tissue damage in Sjogren's syndrome. PMID- 1311548 TI - Preoperative chemotherapy and radiation therapy for stage IIIa carcinoma of the lung. AB - Thirty-six patients with stage IIIa histologically proven non-small cell carcinoma (T3 N2 or T2 N2) underwent concomitant radiation therapy and chemotherapy before pulmonary resection. The therapy consisted of two cycles of continuous infusion of cis-platinum, 25 mg.m-2.day-1 (days 1 through 4) every 4 weeks and concomitant irradiation, 55 Gy, of the tumor and mediastinum. Two to 3 weeks after treatment, the patients were reevaluated for thoracotomy and pulmonary resection. Five patients were found to have unresectable lesions. Thirty-one patients had complete resection, 27 by radical pneumonectomy and 4 by radical lobectomy, giving a resectability rate of 86%. Complete sterilization of lung tumor and mediastinal nodes proven histologically was achieved in 10 patients (28%) and 17 patients (47%). The 3-year survival rate is 61.7% for patients who had resection. Median follow-up is 27 months (range, 6 to 61 months). The preliminary study indicates that preoperative cis-platinum and concomitant radiation therapy is tolerated, appears to increase resectability, and may improve survival in patients with stage IIIa lung cancer. PMID- 1311549 TI - One-stage operation for synchronous primary cancers of the lung and the trachea. AB - A rare combination of synchronous primary adenocarcinoma of the right upper lobe of the lung and adenoid cystic carcinoma of the subglottic trachea was simultaneously managed by lobectomy with lymph node dissection and sleeve resection of the upper trachea through median sternotomy and cervical collar incisions. This combined approach should be a perfectly acceptable one for synchronous tumors of the proximal trachea and of the right upper and middle lobes and left upper lobe of the lung. PMID- 1311550 TI - Interleukin 1 and its relationship to endotoxin tolerance. AB - Endotoxin (lipopolysaccharide [LPS])-induced cytokine release has been implicated in the pathogenesis of sepsis. Sublethal doses of LPS induce tolerance to a septic insult. This study evaluated pretreatment with interleukin 1 (IL-1) against an LPS challenge and examined its relationship to endotoxin tolerance. C3H/HeN mice (N = 100) were injected intraperitoneally with phosphate-buffered saline (control group), IL-1 (200 micrograms/kg), or LPS (1 mg/kg) for 3 days. On day 5, peritoneal macrophages were harvested and assayed for antimicrobial activity (superoxide anion production and Candida albicans phagocytosis). Serum cytokine levels and survival after an LPS challenge on day 5 were also assessed. Pretreatment with IL-1 or LPS significantly increased superoxide anion production, C albicans phagocytosis, and survival compared with pretreatment with phosphate-buffered solution. Interleukin 6 levels significantly decreased in the IL-1 and LPS groups. Peak levels of tumor necrosis factor significantly decreased only in the LPS group. Thus, pretreatment with IL-1 or low doses of LPS may exert protective effects by decreasing levels of interleukin 6 while increasing antimicrobial activity. Mice pretreated with IL-1 were protected from endotoxin despite elevated peak levels of tumor necrosis factor, suggesting a different mechanism for endotoxin tolerance than for tolerance to tumor necrosis factor. PMID- 1311551 TI - Adenoid cystic carcinoma of the breast. AB - Adenoid cystic carcinoma of the breast is a rare neoplasm, with only 140 cases having been reported to date. Data on 123 of these cases are reviewed herein and another case is presented in detail. Several features distinguish this type of breast cancer from more typical histologic types and suggest that it may have a unique tumor behavior. The prognosis appears to be favorable and the incidence of axillary lymph node involvement is lower. Distant metastases are uncommon, but they tend to occur without prior lymph node involvement. This lack of prognostic significance for negative axillary lymph nodes underscores the need for other prognostic markers in this disease and suggests that axillary dissection can be eliminated in most cases. Similarities to typical breast cancer include the incidence of local recurrence and the lack of effect of surgical treatment on distant metastases and overall survival. These data suggest that breast conserving treatment may be applicable to adenoid cystic carcinoma. PMID- 1311553 TI - Purification and characterization of protein kinase C from the nematode Caenorhabditis elegans. AB - Protein kinase C (PKC) of Caenorhabditis elegans was identified by enzymatic activity and [3H]phorbol 12,13-dibutyrate binding after DEAE-Sephacel column chromatography of a crude cytosolic extract. Ca(2+)-dependent activation of nematode PKC was observed in the presence of phosphatidylserine. The enzyme was maximally activated by 1,2-dioleoylglycerol or phorbol 12-myristate 13-acetate in the presence of phosphatidylserine and Ca2+. Hydroxyapatite column chromatography showed only one peak of PKC activity with histone H1 and myelin basic protein as substrates. The enzyme was purified to near homogeneity by sequential chromatography on polylysine-agarose and phosphatidylserine affinity columns. The purified protein showed a molecular mass of 79 kDa on SDS/PAGE. The substrate specificity of the C. elegans enzyme was shown to be different from that of mammalian PKCs. Here we describe some of the properties of the nematode enzyme. PMID- 1311552 TI - Phosphorylation of the C-terminal domain of the Na+/H+ exchanger by Ca2+/calmodulin-dependent protein kinase II. AB - The Na+/H+ exchanger is a pH-regulatory protein that extrudes one H+ ion in exchange for one Na+ ion when intracellular pH declines. A number of studies have shown phorbol ester stimulation of activity in intact cells, leading to the idea that the exchanger is regulated by protein kinase C-mediated phosphorylation in vivo. cDNA encoding the protein has been cloned, and a recent model suggests a large internal cytoplasmic C-terminal domain that may be a site of regulation of the exchanger [Sardet, Franchi & Pouyssegur (1989) Cell 56, 271-280]. We examined this region of the protein using a rabbit cardiac Na+/H+ exchanger cDNA clone. cDNA of the Na+/H+ exchanger, coding for the C-terminal 178 amino acid residues, was cloned into the expression vector pEX-1 and expressed as a fusion protein with beta-galactosidase. The fusion protein reacted with an antibody produced against a synthetic peptide of the C-terminal 13 amino acid residues of the Na+/H+ exchanger, confirming the identity of the expressed protein. Control and experimental pEX-1-Na+/H+ exchanger protein was purified on a p-aminophenyl beta D-thiogalactopyranoside-agarose column. Purified Ca2+/calmodulin-dependent protein kinase II readily phosphorylated the Na+/H+ exchanger protein in a Ca(2+) and calmodulin-dependent manner in vitro, but this region of the protein was not a substrate for purified protein kinase C or for the catalytic subunit of cyclic AMP-dependent protein kinase. Control-expressed beta-galactosidase was phosphorylated to a maximal level of 0.77 +/- 0.17 mol of Pi/mol (mean +/- S.E.M., n = 6) whereas the fusion protein was phosphorylated to a maximal level of 4.09 +/- 0.39 mol of Pi/mol (n = 6), suggesting one site of phosphorylation in beta-galactosidase and three in the C-terminal domain of the Na+/H+ exchanger. Examination of the deduced amino acid sequence of this part of the exchanger reveals three consensus sequences for Ca2+/calmodulin-dependent protein kinase II. These results suggest that the exchanger may be directly regulated in vivo by calmodulin-dependent protein kinase II but not by protein kinase C or cyclic AMP dependent protein kinase. PMID- 1311554 TI - Purification and characterization of a proteolytic active fragment of DNA topoisomerase I from the brine shrimp Artemia franciscana (Crustacea Anostraca). AB - The ATP-independent type I topoisomerase from the crustacean Artemia franciscana was purified to near-homogeneity. Its activity was measured by an assay that uses the formation of an enzyme-cleaved DNA complex in the presence of the specific inhibitor camptothecin. The purification procedure is reported. Purified topoisomerase is a single-subunit enzyme with a molecular mass of 63 kDa. Immunoblot performed on the different steps of purification shows that the purified 63 kDa peptide is a proteolytic fragment of a protein with a molecular mass of 110 kDa. Similarly to the other purified eukaryotic topoisomerases, the crustacean enzyme does not require a bivalent cation for activity, but is stimulated in the presence of 10 mM-MgCl2; moreover, it can relax both negative and positive superhelical turns. The enzyme activity is strongly inhibited by the antitumour drug camptothecin. The enzyme inhibition is related to the stabilization of the cleavable complex between topoisomerase I and DNA. PMID- 1311555 TI - Inhibition of human platelet adenylate cyclase by collagen fibres. Effect of collagen is additive with that of adrenaline, but interactive with that of thrombin. AB - Collagen fibres in suspension have been shown to inhibit adenylate cyclase in human platelet preparations. Direct inhibition by collagen fibres was observed when intact platelets were used, although secondary events such as ADP secretion or prostanoid formation were important contributors to the inhibition of adenylate cyclase after treatment of platelets with collagen. The nature of the direct inhibition caused by collagen has been investigated in platelet membrane preparations, with the following results. (1) Collagen fibres inhibit platelet membrane adenylate cyclase in a dose-dependent manner. (2) Inhibition of adenylate cyclase by thrombin, adrenaline or collagen fibres could be abolished in the presence of guanosine 5'-[beta-thio]diphosphate; half-maximal inhibition was obtained at about 100 microM for the inhibitory action of thrombin, and at about 500 microM for that of either adrenaline or collagen. (3) The action of each ligand was blocked to a similar extent by pertussis-toxin treatment of the platelet membranes. Taken together, these results indicate that the action of collagen, like that of thrombin and adrenaline, is G-protein-dependent. (4) inhibition of adenylate cyclase by collagen fibres was additive with that caused by adrenaline, but co-operative with that caused by thrombin, suggesting that inhibitory pathways exists for collagen and adrenaline which are distinct from, but interactive with, that for thrombin. (5) Modification of the collagen fibres by pepsin treatment attenuated the effects of collagen, whereas heat-denaturation of the collagen fibres completely abolished their effects. These data suggest that the effects of collagen are specific, and depend on the detailed structure of the collagen fibres. PMID- 1311556 TI - The orientation of the three haems of the 'in situ' ubiquinol oxidase, cytochrome bd, of Escherichia coli. AB - The Escherichia coli cytochrome bd complex incorporates three haems as prosthetic groups. In the ferric form these are a predominantly high-spin chlorin (haem d), a high-spin haem b (b595) and a low-spin haem b (b558). The orientations of these three haems have been determined by e.p.r. studies on oriented multilayer preparations of cytoplasmic membrane fragments. The low-spin haem b (b558) and the high-spin haem d are oriented with their haem planes perpendicular to the membrane plane. The high-spin haem b595 is oriented with its haem plane at approx. 55 degrees to the membrane plane. A minor low-spin component, attributable to a low-spin subpopulation of the haem d, is also oriented with its haem plane perpendicular to the membrane plane. PMID- 1311557 TI - Stimulation of glycolysis as an activation signal in rat peritoneal macrophages. Effect of glucocorticoids on this process. AB - 1. Peritoneal macrophages were prepared from control, Escherichia coli-treated and triamcinolone acetonide-treated rats. Control and E. coli-treated rats produced resident and activated macrophages respectively. Glycolysis in these cells was studied by the fructose 2,6-bisphosphate (Fru-2,6-P2) content, lactate release and 6-phosphofructo-1-kinase (PFK-1) and 6-phosphofructo-2-kinase (PFK-2) activities. 2. In activated macrophages, lactate release and Fru-2,6-P2 content were increased several-fold compared with those in resident cells. Moreover, the response of these parameters to phorbol 12-myristate 13-acetate in activated macrophages was greater than for resident cells. 3. PFK-2 activity was moderately increased (about 3-fold), but PFK-1 activity was increased 5-fold in activated macrophages compared with resident cells. Partially purified preparations of PFK 1 were sensitive to Fru-2,6-P2, with K0.5 about 0.25 microM in both control and activated cells. However, the Vmax. of PFK-1 from activated cells was increased. In addition, AMP stimulated PFK-1, but the kinetic pattern was different from that described for Fru-2,6-P2. Moreover there was no difference in the stimulation by AMP of PFK-1 from resident and activated cells. 4. Fru-2,6-P2 content and lactate release in macrophages from triamcinolone acetonide-treated rats were decreased in both resident and activated cells. Also, the glucocorticoid inhibited PFK-1 and PFK-2 activities in both resident and activated macrophages. PFK-1 from triamcinolone acetonide-treated rats was not stimulated by Fru-2,6-P2, whereas the effect of AMP was unchanged. The effects of glucocorticoid seem to be specific for phagocytic cells, since the glucocorticoid treatment increased PFK-1 and PFK-2 activities in liver. PMID- 1311558 TI - Pyrophosphatase-induced Ca2+ release is unrelated to the spontaneous release from inositol 1,4,5-trisphosphate-sensitive Ca2+ stores. PMID- 1311559 TI - Synergistic activation of type III protein kinase C by cis-fatty acid and diacylglycerol. AB - Micromolar concentrations of cis-fatty acid synergistically activate type III protein kinase C with diacylglycerol. This synergistic effect occurs at low concentrations of cis-fatty acid and diacylglycerol, and it is capable of inducing almost full activation of this protein kinase C subtype at a physiologically relevant Ca2+ concentration (2 microM). The synergistic activation mode can be observed even in the absence of Ca2+, but micromolar Ca2+ significantly enhances the type III protein kinase C activation. cis-Fatty acid also augments the diacylglycerol-induced activation of other subtypes (type I and II), although the effect is smaller than that observed in type III. Neither the diacylglycerol- nor the cis-fatty acid-dependent mode of activation can fully activate any of these subtypes at a physiological concentration of Ca2+ (2 microM). Our results suggest that the generation of three second messengers, i.e. the increase in intracellular Ca2+ concentration and the generation of both cis fatty acid and diacylglycerol in the cell, may be necessary signals for protein kinase C activation, particularly for type III protein kinase C. PMID- 1311561 TI - Investigation of guanine-nucleotide-binding protein involvement and regulation of cyclic AMP metabolism in interleukin 1 signal transduction. AB - The involvement of guanine-nucleotide-binding proteins (G-proteins) and regulation of cyclic AMP (cAMP) in interleukin 1 (IL1) signal transduction has been investigated in EL4 and 7OZ/3 cells expressing Type 1 and Type 2 IL1 receptors respectively. Results show that in both cell types IL1 alone failed to induce changes in cellular cAMP levels, and in membrane preparations the cytokine had no significant effect on adenylate cyclase activity. In contrast, forskolin stimulated cAMP levels in cells and membranes. IL1 did not significantly alter GTPase activity or rate of guanosine 5'-[gamma-[35S]thio]triphosphate binding measured in membrane preparations from the EL4 and 7OZ/3 cells. In EL4-cell membrane preparations the kinetics of 125I-IL1 binding were altered in the presence of guanosine 5'-[beta gamma-imido]triphosphate, resulting in the formation of a higher-affinity state for IL1 binding. Adenosine 5'-[beta gamma imido]triphosphate at the same concentration was without effect. These results suggest that IL1 receptor function may be regulated by guanine nucleotides; however, the mechanism appears to differ from that exhibited by conventional G protein-linked receptors. The lack of significant effects of IL1 on cAMP metabolism in these cells suggests that alternative pathways must exist to mediate the intracellular responses to stimulation via both types of the IL1 receptor. PMID- 1311560 TI - Characterization of the low-density-lipoprotein-receptor-independent interaction of beta-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro. AB - beta-Migrating very-low-density lipoprotein (beta-VLDL) is a cholesteryl-ester enriched lipoprotein which under normal conditions is rapidly cleared by parenchymal liver cells. In this study the characteristics of the interaction of beta-VLDL with rat parenchymal cells, Hep G2 cells and human parenchymal cells are evaluated. The binding of beta-VLDL to these cells follows saturation kinetics (Bmax. respectively 117, 106 and 103 ng of beta-VLDL apoliprotein/mg of cell protein), with a relatively high affinity (Kd respectively for beta-VLDL of 10.7, 5.1 and 8.4 micrograms/ml). Competition studies of unlabelled beta-VLDL, low-density lipoprotein (LDL) or acetylated LDL with the binding of radiolabelled beta-VLDL indicate that a LDL-receptor-independent, Ca(2+)-independent, specific recognition site for beta-VLDL is present on rat and human parenchymal cells, whereas with Hep G2 cells or mouse macrophages beta-VLDL recognition is performed by the LDL receptor. The binding of beta-VLDL to Hep G2 cells was down-regulated by 89% by prolonged exposure to beta-VLDL, whereas for human parenchymal and rat parenchymal cells down-regulation of 44% and 20% respectively was observed. Studies with antibodies against the LDL receptor support the presence of a LDL receptor-independent specific beta-VLDL recognition site on rat and human parenchymal cells. It is concluded that a LDL-receptor-independent recognition site for beta-VLDL is present on rat and human parenchymal liver cells. The presence of a LDL-receptor-independent recognition site on human parenchymal cells may mediate in vivo the uptake of beta-VLDL during consumption of a cholesterol-rich diet, when LDL receptors are down-regulated, thus protecting against the extrahepatic accumulation of the atherogenic beta-VLDL constituents. PMID- 1311562 TI - Modulation by betaine of cellular responses to osmotic stress. AB - Various solutes were tested to see if they could modify the responses of SV-3T3 cells to hyperosmotic (0.5 osM) conditions, which cause an inhibition of general cell protein synthesis and of the rate of cell proliferation, coupled with an induction of amino acid transport activity. The added solutes were glycerol, proline, taurine, betaine, dimethylglycine and sarcosine. Of these, betaine produced the most dramatic and consistent effects. Addition of 10-25 mM-betaine to the hyperosmotic medium largely prevented the 90% inhibition of cell proliferation that occurred in its absence. Whether it was added initially or after the cells were exposed to hyperosmotic medium, 25 mM-betaine also converted a 50% recovery of the rate of protein synthesis into 100%. Similarly, the same concentrations of betaine prevented a 30% decrease in cell volume and decreased the induction of amino acid transport via system A by 73%. Lower concentrations of betaine produced smaller but still significant changes in these functional responses. With chick-embryo fibroblasts, under identical hyperosmotic conditions, 25 mM-betaine completely counteracted a 75% inhibition of the rate of protein synthesis. At present it is not clear how betaine modulates these effects of hyperosmolarity on cell functions. PMID- 1311564 TI - Growth factors promote inositol uptake in BC3H1 cells. AB - BC3H1 cells induced to differentiate by serum withdrawal were found to incorporate substantially less [3H]inositol into their phosphoinositides than cells induced to differentiate by growth in the presence of high serum. This decrease was found to be due to a decline in the rate of [3H]inositol uptake by the serum-starved cells. Addition of purified growth factors such as TGF-beta, EGF and FGF to these cells promoted inositol uptake and lead to an increase in the incorporation of [3H]inositol into phosphoinositides. Stimulation of inositol uptake by TGF-beta required at least a 24 hr exposure to the growth factor. These data indicate that growth factors regulate phosphoinositide metabolism at many different levels including at the level of inositol uptake. PMID- 1311563 TI - Use of annexin-V to demonstrate the role of phosphatidylserine exposure in the maintenance of haemostatic balance by endothelial cells. AB - Annexin-V (PAP-I, lipocortin-V) acts as a potent anticoagulant in vitro by binding to negatively charged phospholipids with higher affinity than vitamin K dependent proteins, with a Kd in the 10(-10) M range. The purpose of the present study was to use annexin-V as a probe to assess the catalytic potential of phospholipids in pro- and anti-coagulant reactions in purified systems and at the surface of endothelial cells in culture after stimulation. Procoagulant tissue factor and anticoagulant thrombomodulin activities were compared by using specific two-stage amidolytic assays performed with purified proteins. Procoagulant activity was estimated by the generation of Factor Xa by the Factor VII(a)-tissue factor complex. Anticoagulant activity was estimated by the generation of activated protein C by either the thrombin-thrombomodulin complex or Factor Xa. Annexin-V induced a decrease of 70% of thrombomodulin activity when thrombomodulin (5.4-214 nM) was reconstituted into phosphatidylcholine/phosphatidylserine (1:1, mol/mol) vesicles at 37.5 or 75 microM-phospholipid concentration, the apparent Ki being 0.5 microM at 75 microM lipid. The saturating concentration of annexin-V was dependent on phospholipid concentration, but was independent of the phospholipid/thrombomodulin ratio. By contrast, when thrombomodulin was not reconstituted in vesicles, annexin-V had no effect. At 2 microM, annexin-V totally inhibited the generation of activated protein C by Factor Xa in the presence of 75 microM-lipid, the saturating inhibitory concentration being dependent on phospholipid concentration. At 0.1 microM, annexin-V totally inhibited tissue-factor activity present in crude brain thromboplastin. In the absence of stimulation, human endothelial cells in culture expressed significant thrombomodulin activity and no detectable tissue-factor activity. Basal thrombomodulin activity was only slightly inhibited (less than 15%) by 0.5 microM-annexin-V. Phorbol myristate acetate (PMA) induced the expression of tissue-factor activity and decreased thrombomodulin activity at the endothelial-cell surface. Annexin-V, at a concentration of 16 microM, caused an 80% decrease of tissue-factor activity induced by PMA at 10 ng/ml, whereas it inhibited thrombomodulin activity by only 15% on the same stimulated cells. Our results confirm that annexin-V inhibits, in vitro, procoagulant tissue-factor activity and anticoagulant activities (activation of protein C by the thrombin thrombomodulin complex and by Factor Xa), through phospholipid-dependent mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311565 TI - Identification of human, mouse, and rat retinoic acid receptor alpha using monoclonal antibodies. AB - Monoclonal antibodies that recognize the human, mouse, and rat retinoic acid receptor alpha (RAR alpha) protein have been generated using synthetic peptides. Less well-characterized monoclonal antibodies were also generated against the RAR beta and RAR gamma proteins. Monoclonal antibodies of the IgG1 (R alpha 10) and IgG2a (R alpha 13) isotypes effectively and specifically recognize both the human and mouse RAR alpha protein. Preincubation of the antibodies with the synthetic RAR alpha peptide, but not with the RAR beta or RAR gamma peptides, blocked recognition of the approximately 55 kDa RAR alpha protein on western blots. These monoclonal antibodies also detected differing levels of RAR alpha in various rat tissues. These monoclonal antibodies will serve as powerful reagents to study the structure and regulation of the retinoic acid receptor protein. PMID- 1311566 TI - Induction of Mn-superoxide dismutase by tumor necrosis factor, interleukin-1 and interleukin-6 in human hepatoma cells. AB - Effects of Tumor Necrosis Factor (TNF), Interleukin-1 (IL-1), Interleukin-6 (IL 6) and Interferon-gamma (IFN-gamma) on the expression of Mn-superoxide dismutase (Mn-SOD) protein were investigated in human hepatoma cells, Hu-H1, which revealed resistance to the cytotoxicity of TNF and IL-1. Both TNF and IL-1 enhanced the Mn SOD production to the level of 30- to 40-fold. IL-6 also increased the enzyme protein to 2- to 3-fold of the basal level without any cell proliferative effect. A specific antibody against IL-6 almost completely inhibited the induction of Mn SOD. IL-6, as well as TNF and IL-1, appears to play some role in the Mn-SOD protein expression in human hepatoma cells. PMID- 1311567 TI - Effects of inspired oxygen concentration on in vivo redox reaction of nitroxide radicals in whole mice. AB - Effects of inspired oxygen concentration on metabolism of nitroxide radical were measured in whole mice by using in vivo ESR. Oxygen concentration influenced spin clearance of nitroxide differently in abdomen and head, suggesting that either O2 concentrations or metabolic mechanisms of nitroxide in the two domains were different. PMID- 1311568 TI - Okadaic acid inhibits phosphatidylethanolamine biosynthesis in rat hepatocytes. AB - Okadaic acid, a specific inhibitor of protein phosphatase 1 and 2A, inhibited the synthesis of phosphatidylethanolamine via the CDPethanolamine pathway in isolated hepatocytes. Pulse-chase experiments and measurement of the enzyme activity demonstrated that the inhibition of phosphatidylethanolamine synthesis was not caused by an inhibition of CTP:phosphoethanolamine cytidylyltransferase, the putative regulatory enzyme. However, okadaic acid decreased the cellular diacylglycerol level to 30% of that in control cells. The data suggest that the availability of diacylglycerol limits phosphatidylethanolamine synthesis in okadaic acid-treated hepatocytes. PMID- 1311570 TI - Acceleration of the oxygen reaction in CuA-deficient Nitrosomonas europaea cytochrome c oxidase as revealed by the flow-flash measurement. AB - The oxygen reaction of Nitrosomonas europaea cytochrome c oxidase containing either 2Cu or 1Cu per two heme a molecules was investigated by the flow-flash technique at 20 degrees C. The reaction profiles of the bacterial enzyme were essentially the same as those of bovine heart cytochrome c oxidase, although the rate of the primary oxygen compound formation was much slower. The 1Cu enzyme exhibited higher rates for both primary oxygen compound formation and intramolecular electron transfer than the 2Cu enzyme. This result clearly indicates that CuA is not essential functionally for the oxidation of ferrous heme a moieties, and suggests its structural importance in maintaining the molecular integrity of N. europaea cytochrome oxidase. PMID- 1311569 TI - Ba2+ current oscillations modulated by cyclic AMP and phorbol esters in ras transformed fibroblasts. AB - An oscillatory influx of divalent cations was measured as Ba2+ inward currents (Ba2+ current oscillations) by voltage-clamp recording in v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts after activation with bradykinin or serum. Application of forskolin or dibutyryl cyclic AMP onto DT cells initiated Ba2+ current oscillations. Increasing intracellular cyclic AMP reduced the amplitude but increased the frequency of the Ba2+ current oscillations. Activation of protein kinase C by phorbol esters terminated Ba2+ current oscillations. No inhibition of Ba2+ current oscillations by phorbol esters was observed in down-regulated cells that had been pretreated with phorbol esters for 24 hrs. The results suggest that Ba2+ current oscillations are regulated by intracellular second messengers. PMID- 1311571 TI - The activation of cAMP-dependent protein kinase is directly linked to the stimulation of bone resorption by parathyroid hormone. AB - The present study was performed to characterize the direct involvement of cAMP in the stimulation of bone resorption by parathyroid hormone (PTH), using Sp-cAMPS and Rp-cAMPS, which were the direct agonist and antagonist in the activation of cAMP-dependent protein kinase (PKA), respectively. Bone resorbing activity was estimated as the number of pits formed on the dentine slice and total area of pits per slice in bone marrow cells derived from 2 week-old mice. Dibutyryl cAMP (dbcAMP)(10(-4)M) and Sp-cAMPS (10(-4)M) caused the remarkable stimulation of bone resorption. Although Rp-cAMPS (10(-4)M) did not affect bone resorption by itself, it significantly inhibited dbcAMP- and Sp-cAMPS-induced stimulation of bone resorption. Moreover, Rp-cAMPS (10(-4)M) antagonized 10(-7)M human PTH-(1 34)-induced stimulation of bone resorption, although it did not affect 10(-8)M 1,25(OH)2D3-induced stimulation of bone resorption. Present study indicates the direct involvement of PKA in the stimulation of bone resorption by PTH. PMID- 1311572 TI - Purification of recombinant SH2/SH3 proteins of phospholipase C-gamma 1 and gamma 2 and their inhibitory effect on PIP2-hydrolysis induced by both types of phospholipase C-gamma. AB - In order to examine physiological function of the SH2/SH3 region of phospholipase C-gamma (Z region), we independently expressed cDNA fragments corresponding to the SH2/SH3 region of PLC-gamma 1 and PLC-gamma 2 in Escherichia coli. Although these recombinant proteins were recovered in particulate fractions by centrifugation of cell extracts, they were successfully solubilized by guanidium hydrochloride and then purified to homogeneity by heparin column chromatography. The molecular mass of the proteins was 45 kDa (derived from PLC-gamma 1 and designated as rP45Z) and 38 kDa (derived from PLC-gamma 2 and designated as rP38Z), which was consistent with that as expected from inserted cDNA. We determined the effect of purified rP45Z or rP38Z on PIP2-hydrolyzing activity of either PLC-gamma 1 or PLC-gamma 2 and found that these proteins strongly suppressed the rate of PLC-dependent PIP2-hydrolysis. Furthermore, both rP45Z and rP38Z were phosphorylated at tyrosine residue by epidermal growth factor receptors and their inhibitory effect on PIP2-hydrolysis was significantly decreased by this phosphorylation. These results indicate that the Z region might be involved in autoregulation of PLC-gamma as intrinsic negative regulator. PMID- 1311573 TI - 1,25-Dihydroxycholecalciferol attenuates thyrotropin stimulated iodide accumulation in rat thyroid follicular FRTL-5 cells by reducing iodide porter number. AB - We have recently shown that rat thyroid follicular FRTL-5 cells have functional receptors for 1,25-dihydroxycholecalciferol (1,25- (OH)2D3) and that 1,25-(OH)2D3 attenuates the thyrotropin (TSH) induced iodide uptake. Here we show that the dibutyrylcyclic AMP induced iodide uptake was significantly reduced by 1,25 (OH)2D3, indicating that 1,25-(OH)2D3 affects the cAMP signal pathway beyond cAMP generation. The Vmax of the iodide porter was significantly reduced in 1,25 (OH)2D3 treated cells as compared to cells treated with TSH alone, indicating that 1,25-(OH)2D3 reduces the effective number of iodide porters in FRTL-5 cells. PMID- 1311574 TI - Phosphorylation of a surface receptor bound urokinase-type plasminogen activator in a human metastatic carcinomatous cell line. AB - The 32P-labeled urokinase (uPA) bound to surface receptors of Detroit 562 cells was immunoprecipitated by anti-uPA antibody. Amino acid analysis showed that tyrosines and serines were the acceptors. Inhibition of protein kinases greatly reduced the 32P incorporation, suggesting that the respective cellular src gene product and protein kinase C were involved in the phosphorylations. Proteins purified on chromatographic columns contained two forms of uPA, a high (HMW) and a low (LMW) molecular weight. Tyrosine-phosphorylation occurs in the HMW and A chain. Such modifications might modulate the extracellular activities of uPA. PMID- 1311575 TI - Isolation and characterisation of the human lung NK-1 receptor cDNA. PMID- 1311576 TI - Identity of a differentiation inhibiting factor for mouse myeloid leukemia cells with NM23/nucleoside diphosphate kinase. AB - Mouse myeloid leukemic line M1 cells can be induced to differentiate into the monocyte/macrophage pathway by various inducers. The induction of differentiation of M1 cells can be inhibited by protein inhibitors termed differentiation inhibiting factors (I-factors) in a cell lysate and conditioned medium of differentiation resistant M1 cells. Production of the I-factor activity in resistant M1 cells is well associated with development of resistance of M1 cells to differentiation inducers. We have now purified one of the I-factors from conditioned medium of differentiation resistant M1 cells. The purified I-factor has a relative molecular mass of approximately 16000-17000 Da (16K I-factor). The amino acid sequence of all fragments of the 16K I-factor we have found are identical with Nm23/nucleoside diphosphate kinase (EC2.7.4.6) protein involved in tumor metastasis. The findings indicate that the I-factor, a candidate suppressor protein for differentiation of leukemic cells, is Nm23/nucleoside diphosphate kinase protein. PMID- 1311577 TI - Receptor-mediated mechanisms of peroxisome proliferators. PMID- 1311578 TI - In vitro and in vivo inhibition of rat liver aldehyde dehydrogenase by S-methyl N,N-diethylthiolcarbamate sulfoxide, a new metabolite of disulfiram. AB - In summary, these data provide the first evidence that DETC-MeSO is a natural metabolite of disulfiram, and a potent inhibitor of rat liver mitochondrial low Km ALDH both in vitro and in vivo. It is therefore proposed that, based upon evidence to date, DETC-MeSO appears to be the chemical species to which disulfiram must be bioactivated, and is the metabolite most likely responsible for disulfiram's inhibition of rat liver mitochondrial low Km ALDH in vivo. Characterization of the properties of DETC-MeSO as the metabolite responsible for disulfiram's action as an ALDH inhibitor is presently in the process of being completed. PMID- 1311579 TI - Antioxidant activity of propylthiouracil. AB - Propylthiouracil (PTU) has been demonstrated to reduce alcohol-induced hepatocyte damage and severe alcoholic liver disease. Although the mechanism by which the drug operates is yet to be elucidated, there is evidence that PTU may act as an antioxidant. The present study examines the reaction of PTU with oxygen free radicals and the ability of PTU to directly inhibit peroxidation of a model membrane system. PTU reacted directly with hydroxyl radicals produced by gamma radiolysis. The rate constant for the PTU/hydroxyl radical reaction as determined by steady state competition kinetics with p-nitrosodimethylaniline was 8 x 10(9) L/mol/sec. PTU was less reactive towards superoxide generated by the xanthine/xanthine oxidase system, having a small but significant inhibitory effect on superoxide-induced reduction of cytochrome c only at a concentration of 200 microM. The ability of PTU to protect lipids from peroxidative changes was tested in membranes prepared from linoleic acid. The rate of peroxidation induced by 40 degrees heat decreased from 0.078 to 0.024 mM hydroperoxide/hr in the presence of 0-50 microM PTU. However, this trend was reversed at PTU concentrations above 50 microM. These data suggest that the protective effects of PTU against liver damage may be due to scavenging reactions with hydroxyl radicals in particular and/or its antioxidant potential. PMID- 1311580 TI - Biological activity and molecular interaction of a netropsin-acridine hybrid ligand with chromatin and topoisomerase II. AB - A hybrid molecule, which combines an anilinoacridine chromophore related to the antitumour drug amsacrine (m-AMSA) and a bispyrrole moiety analogous to the antiviral agent netropsin, has been examined for its ability to bind chromatin and to modulate the activity of topoisomerase II. The results show that the presence of histones does not alter the bimodal DNA binding process. Intercalation of the acridine and groove binding of the netropsin part of the drug are both observed with chromatin preparations. Moreover, the hybrid has a clear topoisomerase II-DNA cleavable complex-inducing activity close to that of m AMSA. The role of the two parts of the hybrid ligand is discussed in relation to ternary complex formation. Two cell lines (L1210 leukemia and MCF7 mammary carcinoma) were compared in their sensitivity to the tested ligand. The drug, which appears to be an efficient growth inhibitor of leukemic cells in vitro, reveals moderate activity against P388 leukemia in vivo. The biological activity of the hybrid may derive from a mechanism that involves DNA binding and topoisomerase II inhibition. This study demonstrates that agents which intercalate and bind to the minor groove of DNA simultaneously represent a new class of drugs interfering with topoisomerase II and provide opportunities for the development of new antitumour agents. PMID- 1311581 TI - Reversal of the effects of a low extracellular potassium concentration on the number and activity of Na+/K+ pumps in an Epstein-Barr virus-transformed human lymphocyte cell line. AB - A reduction in the extracellular concentration of potassium to 0.5 mM (low K) in Epstein-Barr (EB) virus-transformed lymphocytes caused changes in the number and activity of Na+/K+ pumps in the cell membrane, with increases in the Bmax and apparent Kd of ouabain binding, and concomitant increases in the Vmax and apparent Km of potassium (rubidium) influx. However, recovery from the effects of low K occurred more quickly than the original up-regulation. Furthermore, there were differences in the time-courses of the separate rates of recovery of the Bmax and Kd of ouabain binding after the cells were returned to normal K, the rate of recovery of the Kd being quicker than that of the Bmax, which was biphasic, with slow and fast rates of recovery. Inhibition of protein synthesis by emetine caused an increase in the rate of recovery of the Bmax of ouabain binding, but no effect on the Kd, suggesting that the slow phase of recovery of the Bmax is attributable to the synthesis and insertion of new protein, while the rapid phase of recovery is independent of protein synthesis and may represent internalization. The results suggested that during up-regulation of pump number in response to low K about 40% of the newly inserted Na+/K+ pumps are normal and the rest are abnormal. The half-time of removal of the abnormal pumps from the cell membrane during recovery from low K stress was 2.8 hr and the half-time of internalization of the normal pumps was 4.3 hr. PMID- 1311582 TI - Inhibition of human neutrophil protein kinase C activity by the antimalarial drug mefloquine. AB - Mefloquine (alpha-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol) , an antimalarial drug, has been shown to inhibit human neutrophil functions, particularly oxygen-dependent bactericidal activity. Since calcium- and phospholipid-dependent protein kinase C (PKC) has a central role in the regulation of this function, we hypothesized that its activity might be altered by mefloquine. We found that mefloquine directly inhibited PKC in a dose dependent manner, with an IC50 of 45 microM. This inhibition appeared to be non competitive with respect to ATP, histone and phosphatidylserine. In addition, mefloquine inhibited the binding of [3H]phorbol 12,13 dibutyrate to PKC, indicating that it interacts with the regulatory domain of PKC. By contrast, mefloquine had little or no effect on neutrophil cAMP-dependent protein kinase or its catalytic subunit. Phorbol myristate acetate-induced protein phosphorylation in intact neutrophils was also inhibited by preincubation with mefloquine at concentrations similar to those inhibiting superoxide anion production. These data suggest that inhibition of neutrophil functions by mefloquine may be due to the inhibition of cellular PKC and that mefloquine could have further biological effects in situations in which PKC is involved. PMID- 1311583 TI - Comparison of two classes of non-peptide drugs as antagonists of neutrophil receptors for f-Met-Leu-Phe. Pyrazolons and iodinated radiographic contrast agents. AB - The radiographic contrast agent sodium diatrizoate (DTR) reportedly inhibits f Met-Leu-Phe-induced chemotaxis in human neutrophils. DTR is also an ingredient of Ficoll-Paque, a density centrifugation medium widely used to purify human polymorphonuclear leukocytes (PMNs). Exposure of PMNs to DTR during preparation had no detrimental effect on subsequent binding characteristics of tritiated f Met-Leu-Phe, probably owing to a rapid dissociation of DTR from the PMN receptors. DTR competed directly with f-Met-Leu-Phe for receptor binding, but was 160- and 640-fold less potent than phenylbutazone and 1,2-diphenyl-4-[3-(1 naphthyl)-propyl]-3,5-pyrazolidinedione (DPN; an analog of phenylbutazone), respectively. Iohexol and the methylamide of DTR did not compete with [3H]f-Met Leu-Phe in receptor binding, supporting the existence of a definite interaction between iodinated aromatic molecules and the f-Met-Leu-Phe receptor. DTR did not inhibit prostaglandin synthesis, as did DPN. Both drugs inhibited chemotactic peptide-induced release of superoxide anion in a concentration-dependent manner, and were relatively selective for f-Met-Leu-Phe, as opposed to C5a. Both drugs at 10 microM interfered non-selectively with chemotactic peptide-induced beta glucuronidase release from PMNs. Available non-peptide antagonists of f-Met-Leu Phe exhibited other pharmacodynamic properties that could make them unsuitable for future in vivo studies designed to probe the physiological role of the receptor. PMID- 1311584 TI - NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase)-mediated two-electron reduction of anthraquinone-based antitumour agents and generation of hydroxyl radicals. AB - The anthraquinone-based antitumour agents mitoxantrone, daunorubicin and ametantrone were found to be substrates for NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase) [QAO] isolated from rat liver. This was indicated by the stimulation of QAO-dependent NADPH oxidation by these agents. This effect followed Michaelis-Menten kinetics and was dependent on the concentration of QAO, inhibited by the specific QAO inhibitor dicumarol (15 microM) and enhanced by the QAO activators bovine serum albumin (0.01%) and Triton X-100 (0.03%). As indicated by the Vmax/Km ratio, mitoxantrone (26.53) was considerably more active than ametantrone (11.25) or daunorubicin (7.35). Metabolism of these anthraquinones was associated with the formation of superoxide anions, hydrogen peroxide and hydroxyl radicals as indicated by electron spin resonance spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide. This is likely to be due to the slow auto-oxidation of the respective dihydroquinones in the presence of molecular oxygen. QAO needs to be considered as a possible route of bioreductive activation of these agents. PMID- 1311585 TI - Modulation of lipoprotein production in Hep G2 cells by fenofibrate and clofibrate. AB - Fenofibrate and other fibrate derivatives are commonly used to treat hyperlipidemia. It is not yet clear how they exert their modulatory effects on plasma lipoproteins. To investigate whether these drugs act on the liver to primarily inhibit very low density lipoprotein production, we utilized the highly differentiated human hepatoma cell line, Hep G2. At concentrations greater than 15 micrograms/mL, fenofibrate caused a 30% decrease in secreted apolipoprotein B (apo B) after 4 days of treatment. Pulse-chase studies demonstrated that this was not due to inhibition of apo B synthesis. Triglyceride synthesis by fenofibrate treated Hep G2 cells was decreased by 30%, and the amount secreted into the medium was reduced by 50%. At a low concentration of drug (5 micrograms/mL), triglyceride secretion was reduced markedly while apo B secretion remained unchanged. Thus, apo B secretion is less sensitive to fenofibrate than the synthesis and secretion of triglyceride, and may be secondary to changes in the latter. Fenofibrate has also been shown to raise plasma high density lipoprotein concentrations. We found that low concentrations of fenofibrate caused a 20-101% increase in secreted apolipoprotein AI (apo AI), and pulse-chase immunoprecipitation studies showed that this was due to an increase in apo AI synthesis. Fenofibrate was compared to clofibrate to investigate whether their relative effects on lipoprotein production in Hep G2 cells were comparable to their relative effects on plasma lipoproteins. Both fibrates decreased the secretion of apo B to the same extent, but only fenofibrate increased apo AI secretion. Fenofibrate was more effective than clofibrate in inhibiting the secretion of lipids by these cells. Thus, the known effects of fenofibrate on plasma lipoproteins can be attributed to its direct modulation of lipoprotein synthesis in the liver cell. Hep G2 cells may thus be useful in testing the relative efficacy of fibric acid derivatives in vitro. PMID- 1311586 TI - Generation of free radicals during the reductive metabolism of nilutamide by lung microsomes: possible role in the development of lung lesions in patients treated with this anti-androgen. AB - The pulmonary metabolism of nilutamide, a nitroaromatic anti-androgen drug leading to pulmonary lesions in a few recipients, has been investigated in rats. Incubation of nilutamide (1 mM) with rat lung microsomes and NADPH under anaerobic conditions led to the formation of the nitro anion free radical, as indicated by ESR spectroscopy. The steady state concentration of this radical was not decreased by CO or SKF 525-A (two inhibitors of cytochrome P450), but was decreased by NADP+ (10 mM) or p-chloromercuribenzoate (0.47 mM) (two inhibitors of NADPH-cytochrome P450 reductase activity). Anaerobic incubations of [3H]nilutamide (0.1 mM) with rat lung microsomes and a NADPH-generating system resulted in the in vivo covalent binding of [3H]nilutamide metabolites to microsomal proteins; covalent binding required NADPH; it was decreased in the presence of NADP+ (10 mM), or in the presence of the nucleophile glutathione (10 mM), but was unchanged in the presence of carbon monoxide. Under aerobic conditions, in contrast, the nitro anion free radical was reoxidized by oxygen, and its ESR signal was not detected. Covalent binding was essentially suppressed. Instead, there was consumption of NADPH and oxygen, and production of superoxide anion and hydogen peroxide. We conclude that nilutamide is reduced by rat lung microsomes NADPH-cytochrome P450 reductase into a nitro anion free radical. In anaerobiosis, the radical is reduced further to covalent binding species. In the presence of oxygen, in contrast, this nitro anion free radical undergoes redox cycling, with the generation of reactive oxygen species. PMID- 1311587 TI - Inhibition of 6-phosphofructo-2-kinase activity by mercaptopurines. AB - The activity of 6-phosphofructo-2-kinase (PFK-2), the enzyme that catalyses the synthesis of fructose 2,6-bisphosphate (Fru-2,6-P2), was inhibited by mercaptopurines in vitro. Inhibition was observed with the purified enzyme from rat liver and bovine heart, and in extracts from rat lymphocytes and hepatoma cells, chick embryo fibroblasts, and human HeLa and lymphoblastoid cells. Half maximal effect was obtained with 0.1-0.2 mM mercaptopurine and maximal inhibition ranged between 50 and 90% depending on the enzyme preparation. The inhibition resulted from a decrease in Vmax with no change in Km for ATP. The inhibition was relieved by treatment of the enzyme with thiol reducing agents, suggesting that it involves the formation of a mixed disulfide between mercaptopurine and thiol group(s) essential for enzyme activity. Incubation of intact lymphocytes or lymphoblastoid cells with 2- or 6-mercaptopurine resulted in a decrease in Fru 2,6-P2 content and lactate release. A decrease in Fru-2,6-P2 content but no change in lactate release was observed in HeLa cells and fibroblasts treated with 6-mercaptopurine but not with 2-mercaptopurine. Treatment of HeLa cells with 6 mercaptopurine resulted in a decreased PFK-2 activity which could be restored by treatment of the cell extract with dithiothreitol. In isolated rat hepatocytes and perfused rat hearts mercaptopurines had little or no effect on the Fru-2,6-P2 content and lactate release. These results suggest that the effect of 6 mercaptopurine of arresting growth in lymphoid cells might involve the inhibition of glycolysis in addition to the known inhibition of de novo purine nucleotide synthesis. PMID- 1311588 TI - Reduced topoisomerase II and elevated alpha class glutathione S-transferase expression in a multidrug resistant CHO cell line highly cross-resistant to mitomycin C. AB - We have isolated a multidrug-resistant derivative of Chinese hamster ovary CHO-K1 cells by exposure to progressively increasing concentrations of Adriamycin. This cell line, designated CHO-Adrr, was 27-fold more resistant than the parental line to Adriamycin and showed similar degrees of cross-resistance to several other topoisomerase II (topo II) inhibitors, including mitoxantrone, daunomycin and etoposide. CHO-Adrr cells showed a lower (4-fold) level of cross-resistance to vincristine and colchicine, drugs associated with the multidrug-resistant phenotype. While CHO-Adrr cells showed no enhanced resistance to several mono- and bi-functional alkylating agents or to UV and ionizing radiation, they were greater than 80-fold resistant to mitomycin C (MMC). There was a 5-fold decreased level of daunomycin accumulation in CHO-Adrr cells compared to CHO-K1 cells and this was associated with increased drug efflux. The resistant cells had amplified multidrug resistance gene (mdr) sequences and overexpressed (mdr) mRNA. Verapamil was able to completely reverse Adriamycin resistance but reversal of MMC resistance was only partial, with residual 23-fold resistance. CHO-Adrr cells expressed a 4-fold reduced level of topo II protein but overexpressed an alpha class (basic) glutathione S-transferase (GST). Analysis of cell hybrids showed that while the level of resistance to Adriamycin dropped by a factor of 3 in CHO K1/CHO-Adrr hybrids compared to CHO-Adrr/CHO-Adrr hybrids, resistance to MMC dropped 10-fold. Thus, CHO-Adrr cells appear to exhibit simultaneously several different drug resistance mechanisms including MDR and GST overexpression, and topo II reduction. PMID- 1311589 TI - Inhibition of human neutrophil leukotriene B4 synthesis by combination auranofin and eicosapentaenoic acid. AB - It has been demonstrated that both auranofin and eicosapentaenoic acid (EPA) have anti-inflammatory properties and both inhibit neutrophil leukotriene B4 (LTB4) synthesis. In the present study, we examined interactions between auranofin and EPA with regard to inhibition of human neutrophil LTB4 synthesis. Auranofin inhibited A23187-stimulated LTB4 synthesis, but the dose required for inhibition of LTB4 was greater than that required for inhibition of other 5-lipoxygenase metabolites; namely, the all-trans isomers of LTB4 and 5-hydroxyeicosatetraenoic acid. These results were explained after a comparison of the rates of synthesis of these 5-lipoxygenase metabolites in the presence and absence of added arachidonic acid which led to the conclusion that leukotriene A hydrolase, the enzyme catalysing the formation of LTB4, was saturated with substrate and rate limiting for LTB4 synthesis during A23187 stimulation. In combination, auranofin and EPA had a simple additive effect on inhibition of the 5-lipoxygenase pathway. Favorable drug/EPA combinations have the potential to provide a beneficial anti inflammatory effect with lower levels of each component than are required when used individually. PMID- 1311590 TI - Modulation of ATPase activity by cholesterol and synthetic ether lipids in leukemic cells. AB - Synthetic ether lipids (EL) exert their antiproliferative action on leukemic cells through localization in the plasma membrane with subsequent biochemical effects which are still being elucidated. In the present study, the modulation of membrane-linked ATPase activity was investigated in relation to changes in membrane fluidity of HL60 and K562 human leukemic cells. Incubation of HL60 and K562 cells with EL under non-cytotoxic conditions caused significant membrane fluidization which was related to the membrane cholesterol (CHOL) levels. HL60 cells, which are sensitive to the cytotoxic action of EL, had a lower basal CHOL content. When HL60 cells were loaded with CHOL, Na+, K(+)-ATPase activity was reduced significantly compared to that of untreated cells. In contrast, CHOL deprived K562 cells had twice the Na+,K(+)-ATPase activity of unmodified K562 cells. Na+K(+)- and Mg(2+)-ATPase activities were stimulated significantly in both cell lines by EL at concentrations lower than 20 microM. This stimulation was greater in cells richer in CHOL, such as K562 cells and CHOL-enriched HL60 cells. In contrast, Na+,K(+)-ATPase in both cell lines was inhibited by EL above 20 microM regardless of the CHOL content. Mg(2+)-ATPase activity was not related to cell CHOL content and was not inhibited by EL above 20 microM. PMID- 1311591 TI - Effect of age on leukotriene B4 production in guinea pig whole blood. AB - We evaluated the effect of age on eicosanoid production in guinea pig blood. Heparinized blood from 7-10-day, 6-week, or 6-month-old guinea pigs was incubated with 150 microM arachidonic acid (AA) for 5 min, followed by stimulation with A23187 (20 micrograms/mL) for an additional 10 min at 37 degrees. The reaction was terminated by centrifugation, and the production of plasma leukotriene (LT) B4 and C4, prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) was determined by enzyme-linked immunoassay (ELISA). LTC4, PGE2, and TXB2 formation were unaffected by age. In marked contrast, production of LTB4 was increased 4- to 5-fold as age increased from 7-10 days (9.51 +/- 2.07 ng/mL) or 6 weeks (8.83 +/- 1.81 ng/mL) to 6 months (40.57 +/- 9.66 ng/mL). To determine the effect of age on the total eicosanoid product profile, blood was stimulated in the presence of [14C]AA, and plasma metabolites were separated by reverse-phase high pressure liquid chromatography (RP-HPLC) and quantitated using on-line radiochemical detection. In addition to increased LTB4 production, a modest increase in 12 hydroxyeicosatetraenoic acid (12-HETE) production was also observed in the 6 month-old animals. Previous studies have demonstrated interference of 12-HETE in the immunoassay of LTB4. Therefore, to validate the authenticity of the plasma leukotriene ELISA measurements, samples were precipitated with methanol and fractionated by RP-HPLC. The fractions co-eluting with [3H]LTB4 or [3H]LTC4 were dried under vacuum and reconstituted in ELISA buffer, and leukotrienes were quantitated. As seen previously, following HPLC purification LTB4 production remained significantly elevated in the 6-month-old guinea pigs, whereas LTC4 production was unaffected by age. To further document the selectivity of this effect on LTB4 production, we evaluated the effect of increasing age on cyclooxygenase or phospholipase A2 (PLA2) activity. Neither cyclooxygenase nor PLA2 activity was elevated as animals matured. In conclusion, the capacity of whole blood to produce LTB4, but not LTC4, TXB2, or PGE2, was elevated markedly in older animals. PMID- 1311592 TI - Retinoyl beta-glucuronide: lack of binding to receptor proteins of retinoic acid as related to biological activity. AB - Retinoid beta-glucuronides have emerged as biologically active, water-soluble, natural retinoids with relatively few toxic and teratogenic effects. The mechanism of action of these glucuronides in the control of epithelial differentiation, growth, and tumorigenesis is unknown. Since retinoyl beta glucuronide (RAG) contains a free carboxyl group, we studied the interactions of RAG with cellular retinoic acid-binding protein (CRABP) and nuclear receptors of retinoic acid (RARs), the possible mediators of the biological action of retinoic acid (RA). RAG did not exhibit any significant affinity to bind either CRABP or RARs. During 24- and 48-hr incubations of RAG in chick cytosol, detectable amounts of RA were generated which interacted with the RA receptors. In chick skin, the biological activity of RAG may be due to this slowly released RA. Other possible modes of action of RAG are suggested. PMID- 1311593 TI - Endothelin-1 stimulates eicosanoid production in cultured human nasal mucosa. AB - Endothelin (ET) has been shown to contract both vascular and nonvascular smooth muscle and to stimulate human nasal glandular secretion of serous and mucous cell products. Some effects of ET are thought to be mediated by eicosanoid production. To explore the direct effect of ET on arachidonate metabolism in cultured human nasal mucosal explants, eicosanoids were measured after ET-1 stimulation. After labeling the explants with [3H]arachidonic acid (AA), supernatant from control and ET-1-treated explants were fractionated by reverse-phase high-performance liquid chromatography (HPLC). The resulting elution pattern suggested the release of prostaglandin (PG) E2 and AA in response to ET-1 stimulation. Radioimmunoassay after HPLC resolution confirmed that ET-1 induced a significantly increased release of PGE2 as well as PGD2, PGF2 alpha, thromboxane B2, and 15 hydroxyeicosatetraenoic acid (15-HETE). Although significant amounts of 15-HETE were generated, cyclooxygenase product generation was most remarkable. Eicosanoid release after ET-1 exposure (10 to 0.1 microM) is concentration dependent and occurs within 1 h. Whereas 15-HETE release was maximal at 4 h, prostanoid production was maximal 1 h after exposure to ET-1. Other assayed AA metabolites, including the peptidoleukotrienes, did not significantly change after ET-1 stimulation. We conclude that ET-1 induces the release of predominantly cyclooxygenase products from cultured human nasal mucosal explants. PMID- 1311594 TI - Activated neutrophils alter contractile properties of the pulmonary artery. AB - Activated neutrophils produce a wide array of products (free radicals, arachidonate metabolites, degradative enzymes), cause hemodynamic effects and increased permeability in isolated blood-free perfused lungs, and evoke direct injury to cultured endothelial cells. The aims of this study were to investigate the response of isolated rat pulmonary arterial rings to activated neutrophils, the role of intact endothelium in these responses, and which neutrophil products were responsible for the observed effects. Neutrophils activated with phorbol myristate acetate caused an initial increase in tension and a subsequent decreased recovery contraction to KCl. Neutrophils activated with formylmethionylleucylphenylalanine also caused an increase in tension but did not result in decreased recovery, suggesting different mechanisms for these two effects. The contractile response was dependent on endothelium, whereas the decline in recovery still occurred in the absence of endothelium. Filtrate from activated neutrophils did not cause the contractile response, but recovery was decreased. Neither addition of catalase + superoxide dismutase nor decreased superoxide release due to prior activation of neutrophils altered the initial contraction or the decline in recovery contractile ability, suggesting that oxygen free radical products were not responsible for either effect. The cyclooxygenase inhibitors (ibuprofen and indomethacin), the thromboxane A2 synthetase inhibitor (OKY-046), and pretreatment of the neutrophils with aspirin inhibited the contractile response but did not prevent the decrease in recovery. A mixture of antiproteases did not protect the arterial muscle from the decline in recovery. Although cyclooxygenase products may be involved in initiating the contraction in response to activated neutrophils, the mechanism resulting in subsequent loss of force-developing ability is unclear. PMID- 1311595 TI - Changes in neutrophil deformability following in vitro smoke exposure: mechanism and protection. AB - We have previously demonstrated a reduction in the deformability of neutrophils, exposed to whole particulate cigarette smoke in vitro, by measuring their ability to filter through a micropore membrane with pore dimensions similar to those of the average pulmonary capillary segment. In this study, we exposed neutrophils to the vapor phase of cigarette smoke and investigated the mechanism of the reduction in neutrophil filterability. Although both stimulated neutrophils and smoke-exposed neutrophils demonstrated an increase in filtration pressures, and thus a reduction in cell deformability, compared with control untreated cells, the spontaneous release of the reactive oxygen intermediates hydrogen peroxide and the superoxide anion was depressed following in vitro smoke exposure and there was no shape change to suggest that smoke-exposed cells were activated. The presence of erythrocytes, plasma, or the antioxidants albumin and glutathione prevented the reduction in cell filterability following smoke exposure, suggesting that in vitro smoke exposure, in our system, was mediated by oxidants. Indeed, the increase in filtration pressures, produced by smoke, could be mimicked by the addition of the oxidant hypochlorous acid. The cytoskeletal inhibitors cytochalasin B and D improved the filterability of smoke-exposed cells, suggesting that smoke may change neutrophil deformability through an effect on the actin component of the cytoskeleton. By contrast, colchicine, a specific inhibitor of the microtubules, had no effect. Preincubation with a monoclonal antibody to the CD18 antigen, to block this major neutrophil adhesive glycoprotein, did not alter the filtration pressure developed by stimulated or smoke-exposed neutrophils, suggesting that increased adhesivity was not the mechanism of the increase in filtration pressures observed following smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311596 TI - Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man. AB - 1. Ageing is associated with a decline in beta-adrenergic responsiveness in several tissues. Reduced beta-adrenoceptor mediated smooth muscle relaxation in aged man has been demonstrated using the dorsal hand vein technique. Isoprenaline and adenosine activate adenylate cyclase through separate membrane bound receptors to induce vasodilatation. 2. To determine the specificity of reduced beta-adrenergic responsiveness in smooth muscle of aged man, and possible sites of the defect responsible, venodilatory responses to isoprenaline, a beta adrenoceptor agonist and adenosine were determined in nine young (age 26 +/- 3 years: mean +/- s.d.) and eight elderly (age 70 +/- 5 years), healthy male volunteers. Veins were partially constricted with the alpha 1-adrenoceptor agonist phenylephrine and increasing doses of adenosine (5 to 1220 micrograms min 1) or isoprenaline (271 ng min-1) were infused. 3. Maximal dilatation induced by isoprenaline was 83 +/- 26% in the young and 51 +/- 34% in the elderly, P = 0.02. Maximal dilatation induced at the highest dose of adenosine (1220 micrograms min 1) was similar in young and elderly: 79 +/- 25% vs 88 +/- 28%, P = 0.26. 4. Adenosine venodilatation was measured before and after infusions of theophylline (6.8 to 135 micrograms min-1) for 30 min in six subjects. Adenosine responsiveness was unchanged following theophylline: 48 +/- 16% to 49 +/- 40%, P = 0.44. 5. The results suggest that the age-associated reduced responsiveness of the beta-adrenergic system in human vascular smooth muscle is not shared by venodilatation mediated by adenosine. PMID- 1311597 TI - The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. AB - 1. Perindopril, an orally active angiotensin converting enzyme inhibitor, was given to 23 hypertensive patients with stable chronic renal failure for 15 days. The dose of perindopril was 2 or 4 mg once a day according to the degree of renal failure. The creatinine clearance of the patients ranged from 6 to 67 ml min-1 1.73 m-2. The pharmacokinetics of perindopril and perindoprilat, its active metabolite, were studied after acute and chronic administration of perindopril. 2. The drug was well tolerated and creatinine clearance was unaltered by treatment. 3. In both groups, steady-state was reached within 3 days of chronic treatment. 4. After both acute and chronic drug administration renal impairment had no effect on perindopril pharmacokinetics but the pharmacokinetics of perindoprilat were altered significantly. After chronic administration the serum accumulation ratio was 1.81 in patients with mild renal failure and 5.35 in patients with severe renal failure. Chronic administration did not modify the renal clearance of perindoprilat nor its elimination half-life. 5. A significant correlation between the renal clearance of perindoprilat and creatinine clearance was observed (r = 0.87 first dose, r = 0.83 last chronic dose). 6. A non-linear relationship between serum perindoprilat concentration and inhibition of angiotensin converting enzyme was described by a modified Hill equation. Values of IC50 were 1.11 +/- 0.07 micrograms I-1 (mean +/- s.d.) in patients with severe renal failure and 1.81 +/- 0.20 micrograms l-1 in patients with moderate renal failure. Chronic administration increased maximal inhibition and decreased the time to maximal inhibition only in patients with severe renal failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311598 TI - 1H NMR spectroscopic studies on the interactions between human plasma antithrombin III and defined low molecular weight heparin fragments. AB - The effects of length and composition upon the antithrombin-binding properties of heparin have been investigated for two series of structurally related heparin oligosaccharides. Each series consists of a tetrasaccharide, hexasaccharide, and octasaccharide heparin fragment composed of alternating hexuronic acid (either iduronate 2-sulfate or glucuronate) and glucosamine 6,N-disulfate residues. These two series represent dominant structural motifs in intact heparin and differ from each other by the presence of a glucuronic acid in one series in place of an iduronate 2-sulfate residue penultimate to the reducing end of the fragment. Perturbations to the 1H resonances in the NMR spectrum of antithrombin upon binding of the two series of heparin fragments are compared to those generated by intact heparin binding, as well as to the effects of binding of a synthetic high affinity pentasaccharide. All of the heparin fragments examined appear to bind to antithrombin at the same site. Three of the heparin fragments (hexasaccharide-2, octasaccharide-2, and octasaccharide-1) produce almost identical perturbations in the antithrombin 1H NMR spectrum compared to binding of intact heparin, including perturbations of resonances from tryptophan 49. This indicates that neither the glucuronic acid nor the trisulfated glucosamine residue (structural elements known to be part of the high-affinity heparin motif) are necessary for the majority of the conformational changes induced upon heparin fragment binding to antithrombin. However, the low anticoagulant activity of these fragments indicates that the changes in protein conformation upon fragment binding, as manifested by these 1H resonance perturbations, are not sufficient for catalytic activation of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311599 TI - Cytochrome c and cytochrome c peroxidase complex as studied by resonance Raman spectroscopy. AB - Complex formation between ferricytochrome c peroxidase (CCP) and ferricytochrome c from yeast [cyt(Y)] and horse heart [cyt(H)] was studied by resonance Raman spectroscopy. On the basis of a detailed spectral analysis of the free proteins, it was possible to attribute changes in the spectra of the complexes to the individual proteins. At pH 7.0 both cyt(Y) and cyt(H) binding induces an increase in the six-coordinate low-spin configuration of CCP from 9% to 19% at the expense of the five-coordinate high-spin state, which drops from 84% to 74%. In the free and complexed state, CCP exhibits a constant fraction of the six-coordinate high spin form (approximately 7%). In addition to affecting the coordination state, there is also a cyt-specific structural response of CCP to complexation. In the cyt(Y)-CCP complex, the peripheral vinyl and propionate substituents of CCP are more rigidly fixed in the protein matrix, whereas binding of cyt(H) only slightly perturbs the conformations of these side chains. The biological significance of the conformational changes in CCP are discussed. In contrast to CCP, there are no detectable structural changes in either cyt(Y) or cyt(H) upon complex formation. PMID- 1311600 TI - Two promoters in the bovine adrenodoxin gene and the role of associated, unique cAMP-responsive sequences. AB - The bovine adrenodoxin gene gives rise to two species of mRNA differing only at their 5'-ends. The synthesis of these two types of mRNA in bovine adrenal cortical cells is regulated transcriptionally in part by ACTH via the action of cAMP. Examination of the 5'-end of the adrenodoxin gene revealed that each mRNA contains sequences derived from a different exon encoding the mitochondrial leader sequence. To define the sequences necessary for the synthesis of these two types of mRNA and to determine if the synthesis of each is driven by a separate promoter, 5'-regions of the adrenodoxin gene were inserted upstream from two different reporter genes and tested for promoter/enhancer regulatory activity by transient transfection into mouse adrenocortical Y1 tumor cells. The results clearly demonstrated that the bovine adrenodoxin gene contains two functional promoters; one, ADXP1, located in the 5'-flanking region gives rise to the minor form of mRNA, and a second, stronger promoter, ADXP2, which maps within intron 1 gives rise to the major form of mRNA. Unique cAMP-responsive sequences were found upstream from each promoter which share no sequence homology to the consensus CRE (cAMP-responsive element). Upon transient expression, the cAMP-responsive sequence associated with the ADXP2 promoter, termed CRS2, confers the cAMP responsiveness to stimulate the transcription of the linked beta-globin reporter gene regardless of whether the adrenodoxin ADXP2 promoter or the beta-globin promoter was utilized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311601 TI - Fuc-GM1 ganglioside mimics the receptor function of GM1 for cholera toxin. AB - The ability of Fuc-GM1 ganglioside to mimic the receptor function of GM1 for cholera toxin (CT) has been investigated. For this purpose, rat glioma C6 cultured cells were enriched with Fuc-GM1 and the responsiveness to CT was compared with that of cells enriched with GM1 ganglioside. Fuc-GM1 was taken up by cells as rapidly and to the same extent as GM1. When comparable amounts of ganglioside were associated, the cells enriched with Fuc-GM1 bound the same amount of 125I-CT as did cells enriched with GM1. Under conditions in which GM1- and Fuc-GM1-enriched cells bound comparable amounts of CT, the Fuc-GM1-treated cells accumulated virtually the same amount of cyclic AMP as did GM1-treated cells, and activation of adenylate cyclase was also similar. The lag time preceding the CT-induced cAMP accumulation was the same in Fuc-GM1- and GM1 enriched cells. High-sensitivity isothermal titration calorimetry (ITC) experiments showed that the association constants of CT with Fuc-GM1 or GM1 ganglioside were comparable (4 x 10(7) M-1 and 1.9 x 10(7) M-1, respectively, at 25 degrees C). Also, the association constants of the B-subunit pentamer with Fuc GM1 or GM1 ganglioside were comparable (about 3 x 10(7) M-1 and 7 x 10(7) M-1, respectively, at 25 degrees C). PMID- 1311602 TI - Primary cutaneous aspergillosis in a heart transplant recipient treated with surgical excision and oral itraconazole. AB - A 24-year-old man underwent orthotopic heart transplantation for treatment of end stage complex congenital heart disease. Six weeks postoperatively, five erythematous skin lesions developed on the patient's right forearm. Punch biopsy revealed Aspergillus. Despite extensive testing, no other potential primary site was located. Because of concern of dissemination, the patient was treated with a combination of local debridement and systemic antifungal therapy with itraconazole. He is presently without signs or symptoms of recurrent disease. PMID- 1311604 TI - Bicarbonate and other buffer systems can enhance the rate of H+ diffusion through mucus in vitro. AB - The effect of various diffusible buffers on mucus H+ permeability, and in particular the potency of the HCO3-/CO2 buffer system relative to other selected buffers is reported here. The diffusional resistance of mucus and water was demonstrated to be dependent on buffer concentration, and the contrast between the two types of layer was most pronounced for low DH+ values near neutrality. This concentration dependence was most marked with mucus layers in the buffer systems investigated. Furthermore, the nature and pKa values of the diffusible buffer systems used in this study had a profound effect on measured DH+. The effect was particularly striking in the case of HCO3- buffer with mucus. Possible implications of these in vitro findings in mucosal protection from acid are discussed. PMID- 1311605 TI - A slow obligatory proton release step precedes hydride transfer in the liver glutamate dehydrogenase catalytic mechanism. AB - We have used the stopped-flow indicator dye method to measure proton release and product formation simultaneously in the initial transient-state portion of the glutamate dehydrogenase-catalyzed oxidative deamination of L-glutamate. We observe a measurably slow release of a proton from the enzyme-NADP-L-glutamate complex. This proton release precedes the hydride transfer step, as indicated by the distinct lag in the product formation signal. We show that the proton release step corresponds to an obligatory intermediate in the reaction sequence. We also find that compounds which are competitive inhibitors of L-glutamate are capable of inducing this phenomenon. We prove that this unanticipated prehydride transfer event cannot be due to the release of an alpha-amino group proton from the substrate. PMID- 1311603 TI - Effect of phenobarbital and 3-methylcholanthrene treatment on NADPH- and NADH dependent production of reactive oxygen intermediates by rat liver nuclei. AB - The effect of inducing the rat liver nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene on NADPH- and NADH-dependent production of reactive oxygen intermediates was evaluated. The inducing agents produced a 2 fold increase in cytochrome P-450, a 50 to 70% increase in NADPH-cytochrome c reductase activity, and a 20 to 30% increase in NADH-cytochrome c reductase activity. Associated with these increases was a corresponding increase in NADPH- and NADH-dependent production of hydroxyl radical (.OH)-like species and of H2O2. Rates of .OH production were inhibited by catalase and partially sensitive to superoxide dismutase. The increase in nuclear production of .OH-like species after drug treatment appears to be due a corresponding increase in H2O2 generation. In contrast to H2O2 and .OH generation, production of thiobarbituric acid-reactive material by nuclei was not increased by the phenobarbital or 3 methylcholanthrene treatment. Redox cycling agents such as menadione and paraquat increased oxygen radical generation to similar extents in the control and the induced nuclei. These results indicate that induction of the nuclear mixed function oxidase system by phenobarbital or 3-methylcholanthrene can result in a subsequent increase in production of reactive oxygen intermediates in the presence of either NADPH or NADH. PMID- 1311606 TI - The interaction of methanol dehydrogenase and its electron acceptor, cytochrome cL in methylotrophic bacteria. AB - The interactions of methanol dehydrogenase (MDH, EC1.1.99.8) with its specific electron acceptor cytochrome cL has been investigated in Methylobacterium extorquens and Methylophilus methylotrophus. The MDHs of these two very different methylotrophs have the same alpha 2 beta 2 structure; the interaction of these MDHs with their specific electron acceptor, cytochrome cL, has been studied using a novel assay system. Electrostatic reactions are involved in 'docking' of the two proteins. EDTA inhibits the reaction by a process involving neither metal chelation nor the 'docking' process. Chemical modification studies showed that the two proteins interact by a 'docking' process involving interactions of lysyl residues on MDH and carboxyl residues on cytochrome cL. When 'zero length', two stage cross-linking was done (with proteins from both bacteria), the alpha subunits of MDH cross-linked with cytochrome cL by way of lysyl groups on MDH and carboxyl groups on the cytochrome. Tuna mitochondrial cytochrome c provided a model for cytochrome cH which is the electron acceptor for cytochrome cL in the 'methanol oxidase' electron transport chain. Tuna cytochrome c was shown to form crosslinked products with carboxyl-modified cytochrome cL. MDH and tuna cytochrome c competed for the same domain on cytochrome cL. It was concluded that MDH reacts with cytochrome cL by an electrostatic reaction which involves carboxyl groups on cytochrome cL and amino groups on the alpha-subunit of MDH. The same domain on cytochrome cL is involved in subsequent 'docking' with its electron acceptor. PMID- 1311607 TI - On the redox equilibrium between H2 and hydrogenase. AB - Redox titrations of the nickel ion in active hydrogenase from Methanobacterium thermoautotrophicum and Chromatium vinosum were performed in the absence of artificial redox mediators, by variation of the H2-partial pressure. These experiments revealed a redox behaviour of the nickel ion which differed remarkably from previous redox titrations in the presence of redox mediators. Notably the EPR signal of the species earlier characterized as monovalent nickel with bound hydrogen, behaved as an n = 2 redox component upon reduction under varying H2-partial pressures. The EPR signal was not a transient one and persisted upon removal of hydrogen. Possible redox processes to explain these observations are discussed. A similar behaviour of nickel was also observed in enzyme as present in intact cells of M. thermoautotrophicum. These results suggest that nickel hydrogenases possess a second site for reaction with H2. PMID- 1311608 TI - Subunit IV of human cytochrome c oxidase, polymorphism and a putative isoform. AB - As part of our study of isoenzyme forms of human cytochrome c oxidase, we purified subunit IV from human heart and skeletal muscle with reversed-phase HPLC and determined the N-terminal amino acid sequences and the electrophoretic mobility. The N-terminus of human heart subunit IV proved to be ragged with 30% of the protein lacking the first three residues. Also a Tyr/Phe polymorphism was observed at residue 16. No differences in N-terminal sequence and electrophoretic mobility were observed between subunit IV of cytochrome c oxidase from human heart and skeletal muscle. Therefore, our results suggest that identical subunits IV are present in cytochrome c oxidase from human heart and skeletal muscle. A putative isoform of subunit IV with a blocked N-terminus was purified from human heart cytochrome c oxidase, which proved to have a different retention time on a reversed-phase column and also a slightly higher electrophoretic mobility on an SDS-polyacrylamide gel compared to the native subunit IV. We could not demonstrate the existence of isoforms of subunit IV in human skeletal muscle. PMID- 1311610 TI - Pulsatile signaling in intercellular communication. Periodic stimuli are more efficient than random or chaotic signals in a model based on receptor desensitization. AB - The efficiency of various patterns of pulsatile stimulation is determined in a model in which a receptor becomes desensitized in the presence of its stimulatory ligand. The effect of stochastic or chaotic changes in the duration and/or interval between successive pulses in a series of square-wave stimuli is investigated. Before addressing the effect of random variations in the pulsatile signal, we first extend the results of a previous analysis (Li, Y.X., and A. Goldbeter. 1989. Biophys. J. 55:125-145) by demonstrating the existence of an optimal periodic signal that maximizes target cell responsiveness whatever the magnitude of stimulation. As to the effect of stochastic or chaotic variations in the pulsatile stimulus, three kinds of random distributions are used, namely, a Gaussian and a white-noise distribution, and a chaotic time series generated by the logistic map. All these random distributions are symmetrically centered around the reference value of the duration or interval that characterizes the optimal periodic stimulus yielding maximal responsiveness in target cells. Stochastically or chaotically varying pulses are less effective than the periodic signal that corresponds to the optimal pattern of pulsatile stimulation. The response of the receptor system is most sensitive to changes in the time interval that separates successive stimuli. Similar conclusions hold when stochastic or chaotic signals are compared to a reference periodic stimulus differing from the optimal one, although the effect of random variations is then reduced. The decreased efficiency of stochastic pulses accounts for the observed superiority of periodic versus stochastic pulses of cyclic AMP (cAMP) in Dictyostelium amoebae. The results are also discussed with respect to the efficiency of periodic versus stochastic or chaotic patterns of hormone secretion. PMID- 1311609 TI - A model for the coordinated development of columnar systems in primate striate cortex. AB - The existence of patchy regions in primate striate cortex in which orientation selectivity is reduced, and which lie in the centers of ocular dominance stripes is well established (Hubel and Livingstone 1981). Analysis of functional maps obtained with voltage sensitive dyes (Blasdel and Salama 1986) has suggested that regions where the spatial rate of change of orientation preference is high, tend to be aligned either along the centers of ocular dominance stripes, or to intersect stripe borders at right angles. In this paper I present results from a developmental model which show that a tendency for orientation selectivity to develop more slowly in the centers of ocular dominance stripes would lead to the observed relationships between the layout of ocular dominance and the map of orientation gradient. This occurs despite the fact that there is no direct connection between the measures of preferred orientation (from which the gradient map is derived) and orientation selectivity (which is independent of preferred orientation). I also show that in both the monkey and the model, orientation singularities have an irregular distribution, but tend to be concentrated in the centers of the ocular dominance stripes. The average density of singularities is about 3/lambda 2 theta, where lambda theta is the period of the orientation columns. The results are based on an elaboration of previous models (Swindale 1980, 1982) which show how, given initially disordered starting conditions, lateral interactions that are short-range excitatory and long-range inhibitory can lead to the development of patterns of orientation or ocular dominance that resemble those found in monkey striate cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311611 TI - Two hypotheses reexamined: gating currents and the number of mobile ions in the Na+ channel. PMID- 1311612 TI - Novel voltage clamp to record small, fast currents from ion channels expressed in Xenopus oocytes. AB - The present report describes a novel technique for voltage-clamping amphibian oocytes in which part of the membrane is isolated by a vaseline gap and the cytoplasmic fluid is exchanged by cutting or permeabilizing the remaining membrane. The main features of this open-oocyte, vaseline-gap voltage clamp are: (a) low current noise (1 nA at 3 kHz), (b) control of the ionic composition of both the internal and external media, (c) fast time resolution (20-100 microseconds time constant of decay of the capacity transient) and (d) stable recordings for several hours. These features allow reliable measurements of tail or gating currents and the new method is especially suitable when either of these currents must be measured to test the effects of mutations introduced into the cDNAs of cloned ion channels. PMID- 1311614 TI - MyoD and myogenin are coexpressed in regenerating skeletal muscle of the mouse. AB - The differential expression of genes triggering myogenesis might cause or reflect differences among myoblasts. Little is known about the presence of MyoD1 and myogenin during the process of regeneration. We therefore examined the expression of MyoD1 and myogenin in muscle regeneration after grafting. Immunostaining of regenerating skeletal muscle of the mouse revealed the presence of both MyoD1 and myogenin. In mononucleated cells the proteins were not detected until shortly before fusion into myotubes. They persisted in the nuclei of regenerated muscle fibers for at least 2 weeks. MyoD1 and myogenin were not detected in nonregenerating control muscle. PMID- 1311613 TI - Voltage-sensitive and solvent-sensitive processes in ion channel gating. Kinetic effects of hyperosmolar media on activation and deactivation of sodium channels. AB - Kinetic effects of osmotic stress on sodium ionic and gating currents have been studied in crayfish giant axons after removal of fast inactivation with chloramine-T. Internal perfusion with media made hyperosmolar by addition of formamide or sucrose, reduces peak sodium current (before and after removal of fast inactivation with chloramine-T), increases the half-time for activation, but has no effect on tail current deactivation rate(s). Kinetics of ON and OFF gating currents are not affected by osmotic stress. These results confirm (and extend to sodium channels) the separation of channel gating mechanisms into voltage sensitive and solvent-sensitive processes recently proposed by Zimmerberg J., F. Bezanilla, and V. A. Parsegian. (1990. Biophys. J. 57:1049-1064) for potassium delayed rectifier channels. Additionally, the kinetic effects produced by hyperosmolar media seem qualitatively similar to the kinetic effects of heavy water substitution in crayfish axons (Alicata, D. A., M. D. Rayner, and J. G. Starkus. 1990. Biophys. J. 57:745-758). However, our observations are incompatible with models in which voltage-sensitive and solvent-sensitive gating processes are presumed to be either (a) strictly sequential or, (b) parallel and independent. We introduce a variant of the parallel model which includes explicit coupling between voltage-sensitive and solvent-sensitive processes. Simulations of this model, in which the total coupling energy is as small as 1/10th of kT, demonstrate the characteristic kinetic changes noted in our data. PMID- 1311615 TI - Patency of side branches after peripheral placement of metallic biliary endoprostheses. AB - During a 28-month period, the authors placed 91 Wallstent endoprostheses in 55 patients with malignant obstructive jaundice. Five patients developed recurrent jaundice between 2 and 60 weeks after stent insertion due to stent occlusion by tumor overgrowth on seven occasions. To assess long-term segmental side-branch drainage through the walls of such endoprostheses, the cholangiograms obtained following stent occlusion were reviewed. In all five patients, evidence of drainage of intrahepatic ducts through the side of the mesh was observed. Although the number of patients in the series is small, this initial experience suggests that long metallic endoprostheses can be placed peripherally in the intrahepatic bile ducts without the potential risk of infection or occlusion of undrained, noninvolved segments. This policy may delay or prevent endoprosthesis occlusion in many patients. PMID- 1311616 TI - Electrophysiological consequences of exposure of hippocampal slices to dihydroxyfumarate, a generator of superoxide radicals. AB - In an effort to understand the damaging actions of free radicals to neuronal electrophysiology, the superoxide generator, dihydroxyfumarate (DHF), was evaluated in slices of guinea pig hippocampus. Using field potential recording techniques, population spikes and population synaptic potentials were recorded in field CA1. Slices were exposed to 3 mM DHF either alone or in the presence of a protectant. DHF did not alter the ability of the afferent volley to generate a synaptic potential, but it did impair the ability of the synaptic potential to elicit a population spike. In addition, DHF induced lipid peroxidation as measured by the thiobarbituric acid assay. Superoxide dismutase (SOD) provided no protection. Instead, SOD treatment promoted DHF damage to synaptic potentials. Catalase alone mitigated the actions of DHF, but only in SOD plus catalase was the DHF-induced electrophysiological deficit and lipid peroxidation completely antagonized. The iron chelator, Desferal, did not protect but promoted synaptic damage. Desferal may be ineffective because of the nitroxide radical formed upon its reaction with DHF. The hydroxyl radical scavenger, dimethylsulfoxide, prevented lipid peroxidation and reduced the DHF-induced deficit but did not completely prevent the impairment of spike generation. These data suggest that DHF exerts its actions through generation of hydrogen peroxide which would further react with tissue iron to produce hydroxyl radicals. PMID- 1311617 TI - Ionic responsiveness in third ventricular hypertonic stimulation of antidiuresis in ducks. AB - Domestic ducks were chronically equipped with a device probing the third cerebral ventricle (VIII) for localized intracerebroventricular (i.c.v.) perfusion. In conscious animals made diuretic by intravenous water loading with 1.0 ml/min hypoosmotic glucose solution (200 mOsm/kg), hyperosmotic i.c.v. stimulations were tested for antidiuretic actions. Artificial cerebrospinal fluid made hypertonic (400 mOsm/kg) by adding sucrose, mannitol, NaCl, LiCl, choline chloride, NaI, NaNO3, LiNO3, CaCl2 or MgCl2 was perfused i.c.v. for 10-15 min at rates of 10-15 microliters/min. Arterial pressure and heart rate were monitored continuously. Hyperosmotic stimulations with non-electrolytes did not induce antidiuresis. Approximately equivalent degrees of antidiuresis were elicited by Na(+)-, Li(+)- and choline salts with a tendency for moderate rises in arterial pressure. Compared to Cl(-)- and I(-)-salts, the effects of NO3(-)-salts were attenuated. Divalent cations caused prolonged antidiuresis, sometimes preceded by initial diuresis, with circulatory side effects unrelated to the changes in renal fluid excretion. It is concluded that the observed antidiuretic effects were mediated by cation-sensitive, rather than osmosensitive neurons on the brain side of the blood-brain-barrier. Their transduction mechanism might consist of poorly selective membrane channels permeable to cations but not to anions. PMID- 1311618 TI - Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary adrenal axis hyporesponsive Lewis rats. AB - We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary adrenal axis function through differential sensitivity to GABA-mediated feedback. PMID- 1311619 TI - The expanding challenge of HIV-associated malignancies. PMID- 1311620 TI - Type Ia glycogenosis associated with hepatocellular carcinoma. AB - The predisposition of preexisting cirrhotic metabolic liver disease to the development of hepatocellular carcinoma is well established. However, the association between glycogenoses (a form of noncirrhotic metabolic liver disease) and the formation of benign and malignant liver tumors is less well known. The sixth case of simultaneous occurrence of glycogenosis type Ia and hepatocellular carcinoma, which occurred in a 34-year-old man referred for advice on therapy for his malignant neoplasm, is reported. Cases previously described in the literature are reviewed and management of this entity in light of the current knowledge in the diagnosis and treatment of hepatocellular carcinoma is discussed. PMID- 1311621 TI - Combined hepatoblastoma and yolk sac tumor of the liver. AB - The authors report a liver tumor that occurred in a 6-month-old boy in which areas of yolk sac and hepatoblastoma were identified. To the best knowledge of the authors, this morphologic pattern has not been reported previously. Theories of histogenesis are discussed. PMID- 1311623 TI - Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma. AB - Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients. PMID- 1311622 TI - The cutaneous form of adult T-cell leukemia/lymphoma in a woman from the Ivory Coast. Clinical, immunovirologic studies and a review of the African adult T-cell leukemia/lymphoma cases. AB - A 36-year-old woman from Ivory Coast, who has lived in France since 1976, had multiple cutaneous nodules and tumors in 1988. Histopathologic studies showed a massive infiltration of the dermis and hypodermis by a diffuse proliferation of mature activated T-cells (CD4-positive, CD25-positive, HLA-DR-positive) with irregular nuclei. The patient did not present with a leukemic picture and only few lymphoid cells with abnormally shaped nuclei were present in the blood. Human T leukemia/lymphoma virus type I (HTLV-I) antibodies were present in the serum and specific HTLV-I pol sequences were detected in the DNA extracted from the tumor nodules and peripheral blood mononuclear cells (PBMC) using the polymerase chain reaction technique. Whereas only a polyclonal integration of HTLV-I provirus was detectable in the PBMC, a clonal integration of three HTLV-I proviruses was demonstrated in the tumor nodules DNA, establishing with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma (ATL). This case illustrates the need for molecular studies to differentiate without ambiguity an ATL from any other type of cutaneous lymphoproliferation, even when it occurs in a HTLV-I-seropositive individual. The situation of HTLV-I-associated ATL in Africa is reviewed. PMID- 1311624 TI - Organic delusional syndrome associated with tamoxifen treatment. AB - The authors describe two cases of tamoxifen-induced organic delusional syndrome that resulted from administration of 40 mg daily for the adjuvant treatment of breast carcinoma. After discontinuation of the tamoxifen therapy, the psychiatric episode resolved within 2 to 4 weeks. Because tamoxifen might cause delusional syndrome, the authors recommend full psychiatric evaluation in appropriate cases. PMID- 1311625 TI - The value of flow cytometric analysis in multicentric glomus tumors of the head and neck. AB - Glomus tumors of the head and neck include those arising from the carotid body, jugular vein, and vagus nerve. Because these cannot be differentiated histologically, when encountering a large tumor mass involving more than one structure in the carotid sheath, one often cannot be sure whether the tumors are from one or more of these structures. The authors performed DNA flow cytometric analysis on a patient with a multicentric glomus tumor on the right side of the neck involving the carotid body, jugular vein, and vagus nerve, in an effort to determine the separate or similar origin of her tumor mass. Different DNA indices, including a double peak for the carotid body tumor, were obtained. There were three aneuploid tumors and one diploid tumor (DNA indices: carotid body 1.78, 2.04; jugular vein 2.20; vagus nerve 1.82). Different synthetic phase fractions were calculated for each aneuploid tumor except the second carotid body peak (carotid body 7.2; jugular vein 3.6; vagus nerve 4.8). The authors conclude that DNA flow cytometry may be useful in confirming the multicentric origin of tumors that encompass more than one histologically similar structure. PMID- 1311626 TI - Carcinoembryonic antigen and carbohydrate 19-9 antigen as markers for colorectal carcinoma in children and adolescents. AB - Colorectal cancer is rare in patients younger than 20 years of age (incidence, 1 in 10 million). Although carcinoembryonic antigen (CEA) and carbohydrate 19-9 antigen (CA 19-9) have been used widely as markers for the efficacy of therapy or detection of recurrent colorectal carcinomas in adults, no studies evaluating their efficacy in children and adolescents have been performed. Between 1986 and 1989, serial measurements of serum CEA and CA 19-9 levels were obtained from 11 patients (aged 8 to 18 years) treated at the institution of the authors. In contrast to the experience in adults, most (9 of 11) of the tumors were localized in the right or transverse colon. Histologically, 10 of 11 carcinomas were mucinous. Most patients had either Dukes' C (5 of 11) or D (5 of 11) lesions. After surgery, all patients were treated with a combination of 5-fluorouracil with Leucovorin (Lederle Laboratories, Pearl River, NY). With the use of the adult normal standards (CEA less than 3.0 ng/ml and CA 19-9 less than 37 ng/ml)6 for the patients, the specificity and sensitivity of CEA were 77% and 64%, respectively, whereas the specificity of CA 19-9 was 79% and the sensitivity was significantly low (10%). The combined specificity of the two markers was 71%, and the combined sensitivity was 60%. On the basis of these results, the authors believe that CEA and CA 19-9 are not effective markers for detection of recurrent or progressive colorectal carcinomas in children and adolescents. PMID- 1311627 TI - Molecular markers for the diagnosis and prognosis of lung cancer. AB - Molecular probes for lung cancer have greatly increased the understanding of the biology of this disease and the preneoplastic changes that precede it. They have confirmed and extended the clinical, pathologic, and biologic reasons for the primary division of lung cancers into small cell and non-small cell lung cancer types. Many molecular changes are present in lung cancers and involve dominant oncogenes and recessive growth regulatory genes. Clinical application of these markers will aid diagnosis, classification, and clinical management. PMID- 1311628 TI - Research and serendipitous secondary findings. PMID- 1311629 TI - Insulin like growth factor I is an autocrine regulator of human colon cancer cell differentiation and growth. AB - The polyanionic compound suramin triggers enterocyte-like differentiation of the human colic adenocarcinoma cell clone HT29-D4. We now demonstrate that suramin interferes with the binding of IGF-I to its receptor at the surface of HT29-D4 cells. Half-maximum inhibition of 125I-IGF-I binding was obtained in the presence of 25 micrograms/ml suramin. Moreover, the drug was able to dissociate 125I-IGF previously bound to its cell surface receptor. Affinity labeling HT29-D4 cells were cultured in the presence of 10 micrograms/ml of alpha-IR3, a monoclonal antibody directed against the binding site of IGF-I, an inhibition of cell proliferation and a stimulation of cell differentiation was observed. After 10 days of treatment with alpha-IR3, HT29-D4 cells formed a regular monolayer of enterocyte-like cells exhibiting an apical brush border and tight junctions delimiting two domains of the plasma membrane (apical and basolateral). Furthermore, we show that IGF-I significantly increased the initial rate of glucose uptake by HT29-D4 cells, while we have previously shown that suramin decreased glucose consumption. From these data we conclude that IGF-I secreted by the cells themselves, stimulates proliferation of HT29-D4 cells via an autocrine mechanism. Blockade of this stimulation by suramin or by a specific monoclonal antibody inhibits cell growth, glucose uptake and triggers the process of enterocytic differentiation. PMID- 1311630 TI - Steroid and growth factor modulation of aromatase activity in MCF7 and T47D breast carcinoma cell lines. AB - The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in basal aromatase activity and different responses to the addition of experimental agents were found in the two cell lines. Aromatase activity in MCF7 cells was significantly stimulated by phorbol 12,13-diacetate [PDA], dibutyryl cyclic AMP [(Bu)2cAMP], transforming growth factor alpha, and epidermal growth factor individually and PDA and (Bu)2cAMP in combination, while it was inhibited by dexamethasone and unaffected by transforming growth factor beta, fibroblast growth factor, platelet-derived growth factor, prolactin, and tamoxifen. Addition of cortisol to MCF7 cells had no effect on aromatase activity at 1 nM, caused suppression of activity at 10 nM and stimulated activity at 100 nM. Aromatase activity in T47D cells was stimulated by transforming growth factor alpha, epidermal growth factor, platelet-derived growth factor, prolactin, dexamethasone, and cortisol individually and PDA and (Bu)2cAMP in combination. It was unaffected by transforming growth factor beta, PDA, (Bu)2cAMP, and fibroblast growth factor. These findings suggest that aromatase activity is induced by agents which stimulate cyclic AMP-dependent protein kinases [e.g., (Bu)2cAMP] and that this effect is potentiated by factors which stimulate protein kinase C [e.g., PDA]. The effect on aromatase activity of growth factors, the actions of which are believed to be mediated by receptors linked to tyrosine kinase activity, is not as clearly defined, with a factor causing stimulation, inhibition, and no change in activity depending on the tissue concerned. Further insight into these differences will require resolution of the molecular mechanisms that mediate the actions of stimulatory and repressive growth factors on aromatase activity of oestrogen-producing cells. PMID- 1311631 TI - Tumor invasion-inhibiting factor 2: primary structure and inhibitory effect on invasion in vitro and pulmonary metastasis of tumor cells. AB - The primary structure of tumor invasion-inhibiting factor 2 (IIF-2) purified from bovine liver (A. Isoai et al., Jpn. J. Cancer Res., 81:909-914, 1990) was determined. A computer homology search of the National Biomedical Research Foundation data bank revealed that IIF-2 is identical to the carboxyl-terminal region, residue number [69-89], of high mobility group 17 which is a DNA-binding non-histone protein. IIF-2 synthesized by an automated peptide synthesizer showed similar invasion-inhibitory activity as compared with the purified factor, when tested with the monolayer invasion assay system using highly invasive rat ascites tumor cells. When examined with the other in vitro assay systems using a modified Boyden chamber, the synthetic IIF-2 suppressed the chemotactic migration of highly metastatic B16 melanoma (B16FE7) cells to fibronectin or laminin and invasion through Matrigel. The IIF-2 inhibited neither the cell proliferation nor the binding of cells to fibronectin or Matrigel and also showed no significant inhibition of Mr 90,000 type IV collagenase (gelatinase) obtained from human schwannoma (YST-3) cells. The formation of lung colonies in mice given injections of B16FE7 and Lewis lung carcinoma cells was significantly reduced by the coinjection of the IIF-2. These results suggest that IIF-2 suppresses tumor invasion by impairing cell motility and inhibits the migration of metastasizing cells through extracellular matrix (extravasation steps) following their arrest in the capillary bed of the lung in vivo. PMID- 1311632 TI - A gene from human chromosome region 3p21 with reduced expression in small cell lung cancer. AB - A combination of cytogenetic and molecular studies has implicated the p21 region of human chromosome 3 as the probable site of a gene the loss of which contributes to the development of small cell lung cancer. We report here the isolation of a gene from this region which is expressed in normal lung tissue and in cell lines derived from a number of different types of tumor, but the expression of which in small cell lung cancer cell lines is undetectable by RNA blot analysis. Although the more sensitive polymerase chain reaction did detect transcripts, a novel quantitative polymerase chain reaction assay showed that their concentration in small cell lung cancer cell lines is less than 3% of that in normal lung. PMID- 1311633 TI - Expression of high-affinity laminin receptor mRNA correlates with cell proliferation rather than invasion in human papillomavirus-associated cervical neoplasms. AB - Induction of the expression of the Mr 67,000 high-affinity laminin receptor gene has been postulated as playing a role in the progression of human tumors to invasive cancers. We tested this hypothesis by examining histopathological sections of a large number of epithelial lesions of the genital tract associated with human papillomaviruses. In situ hybridization was performed with a riboprobe generated from a laminin receptor complementary DNA. Laminin receptor mRNA was expressed primarily in the less differentiated cells in normal squamous tissues and in a spectrum of squamous neoplasms. There was no net induction of mRNA per cell in intraepithelial or invasive squamous neoplasms relative to normal tissue. In contrast, laminin receptor mRNA was not expressed at a detectable level in normal glands of the uterine cervix but was dramatically induced in morphologically abnormal, human papillomavirus-positive glands, irrespective of the genotype of human papillomaviruses present. The induction occurred before any evidence of invasion, and there was no further increase during the transition from adenocarcinoma in situ to invasive carcinoma. We conclude that induction of high-affinity laminin receptor gene expression is associated with the development of malignancies of cervical glandular epithelia, but the increased expression appears to correlate with the proliferative rather than the invasive properties of these cells. PMID- 1311634 TI - Molecular characterization of areas with low grade tumor or satellitosis in human malignant astrocytomas. AB - Malignant astrocytomas often display histopathological heterogeneity. In the present study, we have molecularly characterized different areas within 4 such tumors to determine whether the tissue heterogeneity can be explained by differences in DNA constitution. Two tumors contained low grade areas, and the other 2 had areas with satellitosis. The tumors were examined for loss of heterozygosity with markers from chromosomes 9p, 10, and 17p and for amplification of the epidermal growth factor receptor gene. In each case, the high grade portion of the tumor displayed at least one of these structural alterations. However, identical alterations were found in the associated low grade or satellitosis areas of each tumor. Our data suggest that: (a) genetic alterations associated with tumor progression already occur in histopathologically low grade areas of high grade astrocytoma; (b) satellitosis associated with a high grade astrocytoma has to be considered as part of that tumor; and (c) tissue heterogeneity within a high grade astrocytoma is not a consequence of differences in DNA constitution at the loci that were examined. PMID- 1311635 TI - Tumorigenic transformation and neoplastic progression of human uroepithelial cells after exposure in vitro to 4-aminobiphenyl or its metabolites. AB - A multistep in vitro/in vivo transformation system was used to test the transforming effect(s) of the human bladder procarcinogen 4-amino-biphenyl (ABP) and two putative proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N OH-ABP) and N-hydroxy-4-acetylamino-biphenyl (N-OH-AABP), on a clonally derived nontumorigenic SV40-immortalized human uroepithelial cell line, SV-HUC. SV-HUC were exposed in vitro to concentrations of ABP, N-OH-ABP, or N-OH-AABP that caused a range of cytotoxicity from 5 to 76%. Tumorigenic transformation of SV HUC, as assessed by the ability of the exposed cells to form carcinomas when inoculated s.c. into athymic nude mice, was achieved after a single exposure to ABP, N-OH-ABP, or N-OH-AABP. In the tumorigenic transformation experiments, 28 of 45 mice representing all 15 carcinogen-exposed observation groups formed carcinomas, whereas none of 9 mice from control groups formed carcinomas (P = 0.001). Neoplastic progression of a low grade regressive squamous cell carcinoma, MC-T11, was also achieved in this system after in vitro exposure to ABP, N-OH ABP, or N-OH-AABP. In these progression experiments, 11 of 33 mice representing 7 of 12 carcinogen-exposed observation groups formed persistent, high grade nongressing tumors, while only 1 of 19 untreated MC-T11 controls spontaneously progressed on reinoculation (P = 0.022). Forty independent carcinomas generated in athymic nude mice recapitulated diverse cancer phenotypes (including different growth kinetics and histopathological subtypes and grades) represented in clinical bladder cancers. These results demonstrate for the first time the transforming effects of the potent human carcinogen ABP and two of its proximate N-hydroxy metabolites on a prime human target cell type, HUC. PMID- 1311636 TI - Induction of thioguanine-resistant mutations in human uroepithelial cells by 4 aminobiphenyl and its N-hydroxy derivatives. AB - The mutagenic potentials of the human bladder carcinogen 4-amino-biphenyl (ABP) and three of its proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4 acetylaminobiphenyl (N-OAc-AABP) were tested on a prime human target cell type for carcinogenesis, human uroepithelial cells (HUC). SV-HUC (PC), a near diploid, clonally derived, nontumorigenic SV40-immortalized human uroepithelial cell line that is transformable to tumorigenicity after exposure to ABP and its metabolites, was used for quantitative mutation assays. The end point used was the induction of mutations in the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus, selected using 6-thioguanine resistance (TGr). A single, 24-h exposure of SV-HUC to ABP, N-OH-ABP, N-OH-AABP, or N-OAc-AABP caused a statistically significant, dose-dependent increase in mutation frequency resulting in a 2-30-fold increase in the number of TGr mutants in carcinogen exposed groups compared to untreated controls. These chemicals were similarly mutagenic towards MC-T11, an SV-HUC-derived low grade tumor cell line that was also shown to be responsive to transformation (in a separate study) by ABP, N-OH ABP, or N-OH-AABP as judged by the generation of higher grade tumors. In contrast, the mutagenic potencies of ABP and N-OH-ABP were lower when tested on a subclone of SV-HUC (BC) that is refractory to transformation by these chemicals. Thus, these data support a model of transformation in which ABP as well as its metabolites contribute to tumorigenic transformation and neoplastic progression of HUC by inducing mutations in susceptible target cell genes. PMID- 1311637 TI - Loss of 3p13----p21.2 in tumorigenic reversion of a hybrid between isogeneic nontumorigenic and tumorigenic human uroepithelial cells. AB - Previous studies in our laboratory showed nonrandom losses of chromosome 3p in association with tumorigenic transformation of SV40-immortalized human uroepithelial cells (HUC) to high grade cancers. To test the hypothesis that genes on 3p suppress HUC tumorigenesis, somatic cell hybrids were formed between nontumorigenic SV40-immortalized HUC and an isogeneic derivative transitional cell carcinoma line, MC-T16, that lost 3p on initial transformation. All hybrids were initially tumorigenically suppressed and reversion was always associated with genetic losses, including losses of 3p (Klingelhutz et al., Somatic Cell Mol. Genet., 17: 551-565, 1991). In this paper, we report that the smallest 3p region lost in a tumorigenic hybrid revertant (THR-X) in this system was an unusual interstitial deletion of 3p13----p21.2. Restriction fragment length polymorphism analysis confirmed this loss by showing that THR-X was reduced to homozygosity for D3S30, a 3p13 probe, but remained heterozygous for the distal 3p21.3 probe, D3F15S2. These data, along with our previous report identifying loss of 3p13----p14.2 as the smallest 3p region deleted in association with SV40 immortalized HUC tumorigenic transformation (Klingelhutz et al., Genes Chromosomes Cancer, 3: 346-357, 1991), provide compelling new evidence for a bladder cancer suppressor gene in the 3p13----p21.2 region. PMID- 1311638 TI - p53 mutations cluster at codon 249 in hepatitis B virus-positive hepatocellular carcinomas from China. AB - DNA samples from 36 hepatocellular carcinoma (HCC) patients from China were screened for a specific mutation affecting codon 249 of the p53 gene, recently identified as a hotspot mutation in some HCCs. We detected the tumor-specific p53 codon 249 mutation in 21 (58%) of 36 HCCs examined. Thirteen patients with the specific codon 249 mutation had lost the remaining allele of p53, whereas the remaining eight patients appeared to have retained both copies of the gene. These results suggest that alterations of p53 may be important events in the genesis of HCCs and that point mutation may precede allele loss. PMID- 1311640 TI - Calcium pump isoforms: diversity, selectivity and plasticity. Review article. AB - Ca2+ pumps are essential for removing cytosolic Ca2+ either across the plasma membrane (PM) or into internal organelles such as the sarcoplasmic reticulum (SR). Four genes (PMCA1, PMCA2, PMCA3 and PMCA4) have been reported to encode the PM Ca2+ pumps and three (SERCA1, SERCA2 and SERCA3) to encode the SR Ca2+ pumps. The PM Ca2+ pumps are stimulated by calmodulin, the SR Ca2+ pumps encoded by SERCA1 and SERCA2 are stimulated by phospholamban while the product of SERCA3 may be regulated directly by cAMP-dependent protein kinase. Alternative splicing of the primary transcripts of several of these genes has been reported to occur in a tissue selective manner and for others to alter during ontogeny. For the PM Ca2+ pump, alternative RNA splicing may result in isoforms with altered cyclic nucleotide dependent protein kinase sensitivity. The diversity in distribution of Ca2+ pump isoforms and their regulatory factors when coupled with different Ca2+ entry mechanisms allows for tissue selectivity and plasticity in stimulus response coupling. The roles of various Ca2+ pump isoforms, the rationale behind their tissue selective expression and the plasticity in this expression are among the new challenges to researchers in this field. PMID- 1311639 TI - Na+/Ca2+ exchange in plasma membrane vesicles from a glucose-responsive insulinoma. AB - Plasma membrane vesicles from a glucose-responsive insulinoma exhibited properties consistent with the presence of a membrane Na+/Ca2+ exchange. The exchange was rapid, reversible, and was dependent on the external Ca2+ concentration (Km = 4.1 +/- 1.1 microM). External Na+ inhibited the uptake in a dose-dependent manner (IC50 = 15 mM). Dissipation of the Na+ gradient by 10 microM monensin decreased Na+/Ca2+ exchange from 0.74 +/- 0.17 nmoles/mg protein/s to 0.11 +/- 0.05 nmoles/mg protein/s. Exchange was not influenced by veratridine, tetrodotoxin and ouabain, or by modifiers of cAMP. No effect was seen using the calcium channel blockers, nitrendipine or nifedipine. Glucose had no direct effect on Na+/Ca2+ exchange, while glyceraldehyde, glyceraldehyde-3 phosphate and dihydroxyacetone inhibited the exchange. Na+ induced efflux of calcium was seen in Ca2+ loaded vesicles and was half maximal at [Na+] of 11.1 +/ 0.75 mM. Ca2+ efflux was dependent on [Na+], with a Hill coefficient of 2.7 +/- 0.07 indicating that activation of Ca2+ release involves a minimum of three sites. The electrogenicity of this exchange was demonstrated using the lipophilic cation tetraphenylphosphonium [( 3H]-TPP), a membrane potential sensitive probe. [3H]-TPP uptake increased transiently during Na+/Ca2+ exchange indicating that the exchange generated a membrane potential. These results show that Na+/Ca2+ exchange operates in the beta cell and may be an important regulator of intracellular free Ca2+ concentrations. PMID- 1311641 TI - Evidence for a gelsolin-rich, labile F-actin pool in human polymorphonuclear leukocytes. AB - Filamentous (F) actin is a major cytoskeletal element in polymorphonuclear leukocytes (PMNs) and other non-muscle cells. Exposure of PMNs to agonists causes polymerization of monomeric (G) actin to F-actin and activates motile responses. In vitro, all purified F-actin is identical. However, in vivo, the presence of multiple, diverse actin regulatory and binding proteins suggests that all F-actin within cells may not be identical. Typically, F-actin in cells is measured by either NBDphallacidin binding or as cytoskeletal associated actin in Triton extracted cells. To determine whether the two measures of F-actin in PMNs, NBDphallacidin binding and cytoskeletal associated actin, are equivalent, a qualitative and quantitative comparison of the F-actin in basal, non-adherent endotoxin-free PMNs measured by both techniques was performed. F-actin as NBDphallacidin binding and cytoskeletal associated actin was measured in cells fixed with formaldehyde prior to cell lysis and fluorescent staining (PreFix), or in cells lysed with Triton prior to fixation (PostFix). By both techniques, F actin in PreFix cells is higher than in PostFix cells (54.25 +/- 3.77 vs. 23.5 +/ 3.7 measured as mean fluorescent channel by NBDphallacidin binding and 70.3 +/- 3.5% vs. 47.2 +/- 3.6% of total cellular actin measured as cytoskeletal associated actin). These results show that in PMNs, Triton exposure releases a labile F-actin pool from basal cells while a stable F-actin pool is resistant to Triton exposure. Further characterizations of the distinct labile and stable F actin pools utilizing NBDphallacidin binding, ultracentrifugation, and electron microscopy demonstrate the actin released with the labile pool is lost as filament. The subcellular localization of F-actin in the two pools is documented by fluorescent microscopy, while the distribution of the actin regulatory protein gelsolin is characterized by immunoblots with anti-gelsolin. Our studies show that at least two distinct F-actin pools coexist in endotoxin-free, basal PMNs in suspension: 1) a stable F-actin pool which is a minority of total cellular F actin, Triton insoluble, resistant to depolymerization at 4 degrees C, gelsolin poor, and localized to submembranous areas of the cell; and 2) a labile F-actin pool which is the majority of total cellular F-actin, Triton soluble, depolymerizes at 4 degrees C, is gelsolin-rich, and distributed diffusely throughout the cell. The results suggest that the two pools may subserve unique cytoskeletal functions within PMNs, and should be carefully considered in efforts to elucidate the mechanisms which regulate actin polymerization and depolymerization in non-muscle cells. PMID- 1311642 TI - Increased calmodulin affects cell morphology and mRNA levels of cytoskeletal protein genes. AB - We have previously described stable mouse C127 cell lines in which a CaM mini gene has been expressed in a bovine papilloma virus-based expression vector (Rasmussen and Means: EMBO J. 6:3961-3968, 1987). Elevation of CaM to levels five fold higher than in control cells caused an acceleration in cell cycle progression by reducing the length of the G1 period. When these cell lines were originally isolated it was observed that cells in which CaM levels were increased had a flattened morphology. In this study we have examined the localization of actin, vimentin, and tubulin in these cells as compared to the BPV-transformed control cell line in order to determine if changes in shape were accompanied by differences in the cytoskeletal organization. Cell-cycle-dependent changes in the levels of mRNAs for histone H4, glyceraldehyde-3-phosphate dehydrogenase, beta actin, vimentin, and beta-tubulin have also been examined. Our results indicate that increased CaM causes differences in the organization of microfilaments, intermediate filaments, and microtubules and that these changes are accompanied by selective differences in the cell-cycle-dependent expression of some mRNAs. Elevated CaM was also correlated with a reduced stability of beta-tubulin mRNA. These studies indicate that CaM has pleiotropic effects on cell function and suggest that stable cell lines with altered CaM levels may provide a useful model system for understanding the molecular basis of CaM-dependent regulation of cellular processes. PMID- 1311643 TI - Enhancement of spermidine/spermine N1-acetyltransferase activity by treatment with lithium chloride in Ehrlich ascites tumor cells. AB - The activity of spermidine/spermine N1-acetyltransferase (SAT) was enhanced in Ehrlich ascites tumor cells by the addition of lithium chloride. Na+ did not affect the enzyme activity. Total RNA was isolated from cells treated with LiCl and the relative abundance of the SAT mRNA was measured by Northern blot analysis. The levels in cells treated with LiCl were comparable to those in control cells. In the treated cells, the biological half-life of SAT was approximately 20 min, which was the same as for control cells. When LiCl and H-7, a protein kinase inhibitor, were added simultaneously to culture, the elevation caused by LiCl of SAT activity was reduced. LiCl did not cause maximum enhancement of the enzyme in cells treated beforehand with a higher concentration of TPA. These results suggest that treatment of Ehrlich ascites tumor cells with LiCl enhanced SAT activity during translation, not during transcription or after translation and that the enhancement of SAT by LiCl is probably mediated by protein kinase C. PMID- 1311644 TI - Hepatocyte cytotoxicity induced by various hepatotoxins mediated by cytochrome P 450IIE1: protection with diethyldithiocarbamate administration. AB - The objective of this study was to determine whether the thiol drug, diethyldithiocarbamate (DEDC) and its two metabolites, disulfiram (DS) and carbon disulfide (CS2) could be used as inhibitors of cytochrome P-450IIE1 to protect hepatocytes from cytotoxic xenobiotics. (1) Hepatocytes isolated from rats following pyrazole administration to induce cytochrome P-450IIE1 were much more susceptible to carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN) than hepatocytes from untreated rats. Microsomes isolated from P-450IIE1-induced liver were also much more effective at catalysing a NADPH-dependent metabolism of CCl4 and DMN. The activities of aniline hydroxylase and p-nitroanisole-O-demethylase increased whereas ethoxyresorufin-O-dealkylase activity was much less induced and pentoxyresorufin-O-dealkylase activity was decreased. The P-450IIE1 antibody markedly inhibited the NADPH-dependent metabolism of these compounds indicating that IIE1 is a major catalyst of the microsomal metabolism of CCl4 and DMN. (2) Hepatocytes isolated from rats treated with DEDC or its metabolites, DS and CS2, on the other hand, were resistant to CCl4 and DMN. Microsomes isolated from the liver of animals treated with DEDC or DS or CS2 were also much less effective at catalysing the NADPH-dependent metabolism of the above compounds. DEDC markedly decreased the activities of aniline hydroxylase, p-nitroanisole-O-demethylase and pentoxyresorufin-O-dealkylase but had no effect on ethoxyresorufin-O-dealkylase activity. (3) Hepatocytes isolated from pyrazole-treated rats were also more susceptible to bromobenzene (BB) and naphthalene-induced cytotoxicity than hepatocytes from untreated rats. Furthermore, DEDC or CS2 administration beforehand significantly protected hepatocytes against both xenobiotics. (4) By contrast, hepatocytes isolated from P-450IIE1 induced rats were not more susceptible to lactonitrile or cyclophosphamide. Instead, cyclophosphamide was activated by phenobarbital-induced P-450 isozymes whereas lactonitrile was activated by alcohol dehydrogenase. Hepatocytes isolated from DEDC-treated rats were also resistant to cyclophosphamide but not lactonitrile. (5) The above results suggest that P-450IIE1 catalyses the cytotoxic activation of CCl4, DMN, BB and naphthalene but not of lactonitrile or cyclophosphamide. Furthermore, the administration of DEDC and its metabolites, disulfiram or CS2, inactivates P 450IIE1 so that the hepatocytes become resistant to these hepatotoxins. PMID- 1311645 TI - Improving accuracy of glucose oxidase procedure for glucose determinations on discrete analyzers. AB - We describe a rapid kinetic glucose oxidase (EC 1.1.3.4) procedure for quantifying glucose. Glucose oxidase concentration was reduced from the more usual 20 kU/L to 4 kU/L, and pH was reduced from 7.0 to 6.6. Potassium ferrocyanide (20 mumol/L) and ascorbate oxidase (1 kU/L) were incorporated in the procedure. The assay results vary linearly with glucose concentration from 0 to 50 mmol/L and are unaffected by bilirubin concentrations less than or equal to 600 mumol/L, hemoglobin less than or equal to 12 g/L, Intralipid less than or equal to 4 g/L, urate less than or equal to 1 mmol/L, and ascorbate less than or equal to 2.0 mmol/L. The assay is readily adaptable to most open-system analyzers. PMID- 1311646 TI - Strategies and difficulties in dietary intervention in myocardial infarction patients. AB - Randomized controlled trials along with 'within group' studies of patients with symptomatic coronary artery disease suggest that dietary and other lifestyle changes can halt progression of coronary atherosclerosis, induce regression of pre-existing severe lesions, and reduce the severity or frequency of angina. Varying combinations have been tested, including restriction of dietary total, saturated and polyunsaturated fat using lean meat or vegetarian diets, fish oil supplements, smoking cessation, stress management, and exercise training. The relative importance of each of these remains unclear. In patients with recent myocardial infarction high fish diets appeared effective in reducing both ischaemic heart deaths and total death rates over two years, whereas modest changes in dietary saturated fats or fibre had no influence on outcome. These results suggest that a far more active dietary approach is needed for patients with symptomatic coronary disease. Further research is required into the possible complementary role of dietary measures and drug treatment for reversing the disease process and improving outcome, using new techniques for achieving behavioural change. PMID- 1311647 TI - Modulation of human IgE synthesis by transforming growth factor-beta. AB - Exogenous transforming growth factor-beta 2 (TGF-beta 2) markedly inhibits the interleukin 4 (IL4)-stimulated synthesis of human IgE in three models where the B cell co-stimulation signals are contact dependent. This concerns T cell-dependent IgE production by (i) unfractionated peripheral blood mononuclear cells (PMBC) cultured with IL4 and (ii) highly purified B cells cocultured with irradiated EL4 thymoma cells in the presence of IL4 and phorbol myristate acetate, as well as monocyte-dependent IgE production by rigorously T cell-depleted PBMC cultured with IL4 and hydrocortisone. The suppression is not isotype specific. TGF-beta exerts its effect by inhibiting the proliferation of B cells and perhaps also the differentiation of proliferating B cells. However, at a later stage of differentiation, IgE B cells are refractory to the inhibitory effect of TGF-beta, as shown by the slight but significant increase of the spontaneous secretion of IgE by PBMC of atopic patients. This enhancement is due to the suppression of endogenous interferon-gamma production. Most interestingly the synthesis of IgE by highly purified B cells costimulated with IL4 and Epstein-Barr virus is unaffected by TGF-beta. It is concluded that TGF-beta mainly acts by inhibiting IL4-supported B cell proliferation; however, its effects depend upon the B cell costimulation signals that are required together with IL4 for the induction of IgE synthesis. PMID- 1311648 TI - Renal haemodynamic, hormonal and excretory effects of low-dose atrial natriuretic factor infusion in renal transplant recipients. AB - 1. In experimental studies, activation of renal sympathetic nerves attenuates the natriuretic response to atrial natriuretic factor. We therefore investigated the response to low-dose infusion of atrial natriuretic factor in renal transplant recipients. 2. Eight male cyclosporin-treated renal transplant recipients received human-alpha atrial natriuretic factor (1-28) at a dose of 1.2 pmol min-1 kg-1 or placebo for 2 h in a placebo-controlled, randomized, cross-over study. The plasma atrial natriuretic factor concentration rose from 18.5 to 49.2 pmol/l in association with an immediate natriuresis (a rise of 49.1 mumol/min in the first 30 min, P less than 0.05; peaking at a 61% increase from baseline, P less than 0.01), diuresis (from 3.37 to 7.46 ml/min) and a threefold rise in urinary cyclic GMP excretion. 3. In response to infusion of atrial natriuretic factor, the packed cell volume rose by 4.2% (P less than 0.001) and the filtration fraction by 5% (from 22 to 27%, P less than 0.05), but there was no significant change in renal plasma flow, glomerular filtration rate or mean arterial blood pressure. Likewise, the plasma catecholamine concentrations, plasma renin activity and serum erythropoietin concentration remained unchanged. 4. The sensitivity of the renal allograft to plasma atrial natriuretic factor concentrations in the high physiological range suggests a role for endogenous atrial natriuretic factor in the modulation of graft function. Furthermore, the immediate natriuretic response to atrial natriuretic factor in the effectively denervated transplant kidney, in contrast to the delayed response seen in normal subjects, may imply that sympathetic nerves have an inhibitory effect on the renal response to atrial natriuretic factor in normal man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311649 TI - Effect of haemodialysis on plasma levels of brain natriuretic peptide in patients with chronic renal failure. AB - 1. Plasma human brain natriuretic peptide-like immunoreactivity (hBNP-li) was measured in ten patients with chronic renal failure before and after 4 h of haemodialysis. 2. Plasma hBNP-li was elevated in all patients before dialysis (mean +/- SEM 21.0 +/- 3.8 pmol/l) compared with healthy control subjects (1.3 +/ 0.2 pmol/l, n = 11), but showed considerable inter-patient variability. Before dialysis plasma hBNP-li bore no relationship to the serum creatinine level or to the mean blood pressure. 3. Plasma hBNP-li fell significantly (P = 0.04) during 4 h of haemodialysis. The fall in plasma hBNP-li correlated significantly with the degree of postural blood pressure drop (r2 = 0.44, P = 0.05) and with the fall in body weight (r2 = 0.64, P less than 0.01) after haemodialysis. In all patients, plasma hBNP-li at the end of treatment remained above that in healthy subjects. 4. There was no significant correlation between the fall in plasma hBNP-li and the fall in serum creatinine level, and between the fall in plasma hBNP-li and the fall in supine systolic or diastolic blood pressure, during haemodialysis. 5. We have shown that plasma hBNP-li is elevated in patients with chronic renal failure and is decreased during haemodialysis. The fact that the plasma hBNP-li was not reduced to normal by haemodialysis despite restoration to normovolaemia gives tentative support to the view that, in addition to hypervolaemia, another factor may also be responsible for the elevated plasma hBNP-li seen in these patients. PMID- 1311650 TI - Coronary haemodynamic effects of angiotensin II in mild essential hypertension in man. AB - 1. The present investigation was carried out to elucidate the possible role of the renin-angiotensin system in modulating coronary vasomotor responses in eight patients with uncomplicated mild essential hypertension with no electrocardiographic-echocardiographic evidence of left ventricular hypertrophy. 2. Systemic and coronary haemodynamics were monitored at baseline and during intravenous infusion of angiotensin II at a subpressor dose (3 ng min-1 kg-1 for 15 min) and at a pressor dose (13 ng min-1 kg-1 for 15 min) both at rest and during handgrip exercise. Infusion of the subpressor dose of angiotensin II decreased coronary sinus blood flow at rest (207 +/- 10 versus 182 +/- 9 ml/min, P less than 0.05) without a significant change in mean arterial pressure, heart rate or mean right atrial pressure. The performance of handgrip at baseline and during infusion of the subpressor dose of angiotensin II resulted in 55% (321 +/- 13 versus 207 +/- 10 ml/min) and 44% (263 +/- 16 versus 182 +/- 9 ml/min) increases in coronary sinus blood flow, respectively, in response to comparable increments in the rate-pressure product. At rest, infusion of the pressor dose of angiotensin II increased both coronary sinus blood flow (235 +/- 11 versus 207 +/ 10 ml/min, P less than 0.01) and the rate-pressure product (134 +/- 5 versus 111 +/- 8 mmHg beats/min, P less than 0.01). The increase in coronary sinus blood flow during isometric exercise was less than control (309 +/- 18 versus 321 +/- 13 ml/min, P less than 0.01). 3. It is thus concluded that (1) the opposite effects of angiotensin II on coronary blood flow are dose-dependent, and that (2) angiotensin II competes with the ability of the coronary arteries to dilate during handgrip exercise. PMID- 1311651 TI - Mutual interactions of respiratory sinus arrhythmia and the carotid baroreceptor heart rate reflex. AB - 1. In six healthy subjects the amplitude and phase of respiratory sinus arrhythmia were determined at five different respiratory cycle lengths ranging from 3 to 9.5 s. 2. At each respiratory cycle length the carotid baroreceptor heart rate reflex response was determined by cyclical neck suction at -40 mmHg at five different cycle lengths covering the same range of 3-9.5 s. 3. The application of cyclical neck suction increased the amplitude of respiratory sinus arrhythmia in all but the longest respiratory cycle lengths. 4. With increasing respiratory cycle length the amplitude of sinus arrhythmia increased, and R-R intervals were at their longest at an earlier phase of the respiratory cycle. Similarly, with increasing suction cycle length the amplitude of the cardiac interval response increased and the phase angle decreased. 5. The cardiac interval responses to respiration and to neck suction at different frequencies were independent of each other, the heart rate at any moment resulting from the algebraic summation of the two responses. PMID- 1311652 TI - Pressor response to a postural change in cirrhosis: an experimental study in the CCl4-treated rat. AB - 1. Systemic hypotension, blunted cardiovascular responsiveness to noradrenaline and an abnormal hypertensive pressor response to a postural change have been described in cirrhotic patients. 2. We have examined the role of blunted responsiveness in these abnormalities by studying basal arterial blood pressure and its response to a postural change (vertical head-up 90 degrees tilting) in conscious and pithed CCl4-treated (cirrhotic) rats, as well as assessing the pressor response to noradrenaline in vivo and the vascular contractile response to noradrenaline in vitro. 3. A diminished hypotensive response to a change in posture was found in pre-cirrhotic portal hypertensive rats, whereas an inverted hypertensive pressor response in the face of systemic hypotension occurred in the cirrhotic rats with portal hypertension. 4. The inverted pressor response was abolished in the pithed portal hypertensive cirrhotic rats. 5. The pressor response to noradrenaline in vivo in conscious cirrhotic rats and the vascular contractile responsiveness to noradrenaline in vitro were intact. 6. We conclude that blunted responsiveness to noradrenaline is not a contributory factor to the development of systemic hypotension or the inverted pressor response to a change in posture in cirrhosis. PMID- 1311653 TI - Comparative study of pressor and heart rate responses to angiotensin II and noradrenaline in pregnant and non-pregnant women. AB - 1. Twenty-eight healthy non-pregnant women and 28 women in the first or second trimester of pregnancy were studied. They were given an incremental intravenous infusion of either noradrenaline or angiotensin II. Pressor and heart rate responses were documented. 2. Dose-pressor response curves were constructed for the two agents in pregnant and non-pregnant women (n = 14 in each group). The regression parameters of slope and intercept were calculated, and were used to derive the variables of dose required to elicit a 10 mmHg rise in systolic or diastolic blood pressure. 3. The pressor response to angiotensin II was diminished in pregnancy, with approximately twice the dose being required to raise the systolic or diastolic arterial blood pressure as in non-pregnant subjects. 4. The systolic pressor response to noradrenaline was slightly diminished in pregnancy, but the diastolic pressor response was unchanged. There were no significant differences between the doses of noradrenaline required to elicit a 10 mmHg rise in systolic or diastolic arterial blood pressure in pregnant or non-pregnant subjects. 5. There was a diminution in the bradycardia evoked in response to both hormones in pregnancy. 6. We conclude that the well documented pressor insensitivity to angiotensin II during pregnancy is a specific phenomenon, not a manifestation of a generalized reduction in vascular reactivity. PMID- 1311654 TI - Location of enkephalinase and functional effects of [Leu5]enkephalin and inhibition of enkephalinase in the feline main pancreatic and bile duct sphincters. AB - 1. Morphological studies have demonstrated enkephalinergic nerve fibres in proximity to the sphincter of Oddi, and opiates are known to contract this sphincter. In this study, the flow resistances in the common bile duct and main pancreatic duct sphincters were studied simultaneously in anaesthetized cats using a perfusion technique. 2. Naloxone did not affect the activity of these sphincters under basal conditions, indicating that there is no basal enkephalinergic tone. 3. The response to [Leu5]enkephalin (0.015-15 micrograms/kg), morphine (1 mg/kg) and ketamine (10 mg/kg) was a naloxone sensitive increased activity in the sphincters with a raised frequency of phasic contractions. The threshold dose for an effect of [Leu5]enkephalin on the sphincter of Oddi was 0.015 microgram/kg and a maximal response was observed at 0.75 microgram/kg. There were no differences in the response of the main pancreatic duct sphincter and the bile duct sphincter to the different drugs. 4. Immunoautoradiographic studies demonstrated enkephalinase in the sphincter++ of Oddi. 5. Acetorphan (3 mg/kg intravenously), which inhibits endogenous enkephalinase both in the peripheral and the central nervous system when administered parenterally, caused a naloxone-sensitive contraction, whereas thiorphan (3-20 mg/kg), an enkephalinase inhibitor that does not easily penetrate the blood-brain barrier, had no effect on the sphincter of Oddi. 6. These results show that endogenous and exogenous opiates influence the function of the feline sphincter of Oddi and that enkephalins may be involved in the physiological control of this sphincter, although not under basal conditions. PMID- 1311655 TI - Isolation and purification of human biliary vesicles with potent cholesterol nucleation-promoting activity. AB - 1. Cholesterol nucleation is a critical step in the formation of cholesterol gallstones. This nucleation takes place after aggregation and fusion of cholesterol-rich biliary vesicles, a process probably modulated by biliary proteins. The present study was conducted to identify specific proteins associated with native cholesterol-rich biliary vesicles and to explore their effect on the cholesterol-nucleation time of supersaturated artificial bile. 2. Hepatic bile was obtained from six patients with cholesterol gallstone disease. Biliary vesicles were isolated by ultracentrifugation and were purified by gel filtration chromatography. A small amount of protein (less than 1% by weight) remained associated with the purified cholesterol-rich biliary vesicles. The electrophoretic profile of these proteins was remarkably similar in all six patients, showing the presence of at least six polypeptides (of molecular mass from 52 to 200 kDa), five of them having carbohydrate residues (except the 52 kDa one). The effect of reconstituted biliary vesicle solutions, containing their specific vesicular proteins, on cholesterol-nucleation time was studied by mixing the vesicle solution with artificial supersaturated bile. A potent cholesterol pronucleating activity, reflected in a 20-70% reduction in nucleation time, was present in the biliary vesicle solutions compared with control solutions having a similar lipid composition. The pronucleating activity disappeared on heating and was not detected in the micellar fraction containing the major proportion of biliary proteins. 3. These results indicate that cholesterol-rich biliary vesicles containing a unique and defined glycoprotein profile can be isolated and purified from human hepatic bile. The potent cholesterol-pronucleating activity of the biliary vesicles from patients with gallstones was unrelated to their lipid composition or cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311656 TI - Differences in ouabain-induced natriuresis between isolated kidneys of Milan hypertensive and normotensive rats. AB - 1. Several observations support the hypothesis that in rats of the Milan hypertensive strain elevated levels of a circulating ouabain-like factor might normalize the elevated Na+ reabsorption, but, on the other hand, might contribute to the development of hypertension. 2. As the receptor occupancy of this endogenous factor seems to be reversible, the aim of our study was to test, in vitro, the hypothesis of its presence in isolated kidneys from Milan hypertensive rats by studying the response to exogenous ouabain before and after prolonged washing. 3. The kidneys were isolated from adult Milan hypertensive rats and from age-matched normotensive controls and ouabain was given at two different experimental time intervals: shortly (15 min) after washout or after a further 60 min of washout (75 min in total). Comparative experiments with the diuretic hydrochlorothiazide were performed using the same protocol. 4. Ouabain given after 15 min of perfusion caused an increase in renal vascular resistance, diuresis and natriuresis; these haemodynamic and tubular responses were similar in kidneys from both Milan hypertensive and Milan normotensive rats. If given after the washout period, ouabain caused a comparable increase in renal vascular resistance, but a significantly greater natriuresis in kidneys from Milan hypertensive rats as compared with kidneys from Milan normotensive rats. On the other hand, hydrochlorothiazide caused similar natriuresis in kidneys from both strains after washout. 5. These results support the hypothesis that a factor, capable of interacting with the ouabain receptor on the Na+/K(+)-ATPase of tubular cells, is present in the kidney of adult Milan hypertensive rats and that it can be removed by prolonged washout. PMID- 1311657 TI - Adaptation to a diet low in protein: effect of complex carbohydrate upon urea kinetics in normal man. AB - 1. Urea kinetics were measured by using prime/intermittent oral doses of [15N15N]urea in five healthy men taking formula diets adequate in energy and containing either 70 or 35 g of protein/day. In some studies the low-protein diet was supplemented with non-starch polysaccharides in the form of ispaghula husk or ripe bananas. 2. On the 70 g of protein/day diet urea production was 132% of intake. Only 54% of the urea produced was excreted in the urine with 46% being salvaged in the colon; 90% of the salvaged nitrogen was retained in the metabolic nitrogen pool. 3. On the 35 g of protein/day diet the small decrease in urea production rate compared with that on the 70 g of protein/day diet was not significant, but only 36% of the urea produced was excreted in urine, with the majority, 64%, being salvaged. 4. The extent of urea-nitrogen salvaging on the 35 g of protein/day diet was similar in magnitude to the decrease in nitrogen intake, with the effect that the sum of intake and salvaged nitrogen did not differ between the 35 and the 70 g of protein/day diets. This implies that quantitative control is exerted over the rate at which urea nitrogen is salvaged. 5. The addition of non-starch polysaccharides to the 35 g of protein/day diet had a demonstrable effect upon faecal weight and composition, but did not exert any significant influence upon urea kinetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311658 TI - Effects of early amino acid administration during total parenteral nutrition on protein metabolism in pre-term infants. AB - 1. We investigated the effects of starting amino acid administration on post natal day 2 on protein turnover and nitrogen balance in appropriate-for gestational-age, very-low-birth-weight infants. Eighteen infants were divided into two groups. Group A received from day 2 onwards an amino acid solution, whereas group B started on this solution after day 4. Both groups were exclusively parenterally fed, 200 kJ day-1 kg-1 on post-natal days 3 and 4. Group A (birth weight 1.5 +/- 0.3 kg) received 4.6 g of glucose, 1.9 g of fat and 2.3 g of amino acids day-1 kg-1 body weight. Group B (birth weight 1.4 +/- 0.2 kg) received 7.0 g of glucose and 1.9 g of fat day-1 kg-1 body weight. 2. At post natal day 3, a primed constant infusion of 3 mg of [15N]glycine day-1 kg-1 was given. Protein flux, protein synthesis and protein breakdown were calculated from the 15N enrichment in urinary ammonia. In five out of nine infants in group B no plateau of 15N enrichment in urinary urea could be detected, whereas in group A two out of nine infants did not reach a plateau. For this reason we did not use the end product urea for our calculations. 3. The administration of the amino acids resulted in a higher protein flux (6.9 +/- 1.5 g day-1 kg-1 versus 5.2 +/- 0.9 g day-1 kg-1) and a higher protein synthesis rate (6.0 +/- 1.4 g day-1 kg-1 versus 4.6 +/- 0.8 g day-1 kg-1) in group A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311659 TI - Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat. AB - 1. Administration of tumour necrosis factor (cachectin) and of interleukin-1 alpha increased the plasma level of nonesterified fatty acids in fed rats, and in the case of interleukin-1-alpha the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis. There were parallel increases in the plasma level of triacylglycerols. Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations. 2. In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines. The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats. The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-alpha. Parallel changes occurred in hepatic ketone bodies. 3. It is concluded that tumour necrosis factor-alpha and interleukin-1-alpha are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states. PMID- 1311660 TI - Danazol induces resistance to both insulin and glucagon in young women. AB - 1. Danazol elevates plasma insulin, plasma glucagon and serum low-density lipoprotein concentrations and reduces the serum high-density lipoprotein concentration. 2. Associations between these disturbances were studied in 17 women receiving danazol therapy for endometriosis. Eleven women underwent intravenous glucose tolerance tests with measurement of plasma glucose, insulin, C-peptide and glucagon concentrations and modelling analysis of intravenous glucose tolerance test concentration profiles. Six women underwent glucagon sensitivity tests. Serum concentrations of lipids and lipoproteins were measured in all cases. 3. Danazol reduced the fasting plasma glucose and insulin concentrations, but markedly raised the fasting plasma glucagon concentration. The insulin and C-peptide responses to the intravenous glucose tolerance test were increased twofold and the net decrement in glucagon concentration was increased tenfold. The glucose response to the intravenous glucose tolerance test was unaffected. Insulin sensitivity was reduced by 55%. Both first-phase plasma insulin responsiveness and net first-phase pancreatic insulin secretion were increased; insulin half-life was prolonged. The glucose response to the glucagon sensitivity test was reduced on treatment. The calculated low-density lipoprotein cholesterol level rose by 20%, whereas high-density lipoprotein cholesterol level fell by 47%. None of these changes in serum lipoprotein levels correlated with changes in insulin metabolism. In general, metabolic changes normalized after 3 months. 4. Danazol increases the sensitivity of pancreatic insulin and glucagon secretion to glucose. Danazol-induced insulin and glucagon resistance could be due to receptor down-regulation resulting from hypersecretion of insulin and glucagon. PMID- 1311662 TI - Contractile properties and susceptibility to exercise-induced damage of normal and mdx mouse tibialis anterior muscle. AB - 1. The functional properties of tibialis anterior muscles of normal adult (C57BL/10) and age-matched dystrophin-deficient (C57BL/10 mdx) mice have been investigated in situ. Comparisons were made between tibialis anterior muscle strength, rates of force development and relaxation, force-frequency responses and fatiguability. Subjecting mdx and C57 muscles to a regimen of eccentric exercise allowed the hypothesis to be tested that dystrophin-deficient muscles are more susceptible to exercise-induced muscle damage. 2. mdx muscles were, on average, 30% stronger than C57 muscles and almost 80% heavier, but both had similar muscle lengths. Thus, although mdx muscles were stronger in absolute terms, their estimated force per unit cross-sectional area was significantly less than that of C57 muscles. 3. The force-frequency relationships of C57 and mdx muscles differed in that whilst, at 40 Hz, the former developed 70% of the force developed at 100 Hz, the latter developed only 55% of the maximal force. Twitch force was normal in mdx muscles, but contraction time was shortened, and the consequent reduction in fusion frequency probably explains the force-frequency differences observed between the two groups. 4. mdx muscles were less fatiguable than normal muscles when stimulated repeatedly at a frequency of 40 Hz. It is possible that the lower relative force at 40 Hz in mdx muscles entailed a lower energy demand and thus a slower rate of fatigue than seen in normal muscles. 5. Eccentrically exercised C57 muscles showed a large loss of maximal force for up to 12 days after exercise. Maximal force loss occurred 3 days after exercise (55% of non-exercised tibialis anterior muscle), which also corresponded with the period of greatest fibre necrosis. C57 muscles showed a significantly reduced 40 Hz/100 Hz force-frequency ratio at 1 and 3 days after exercise. This was primarily due to a reduced twitch amplitude rather than to a change in the time course of the twitch. It is unlikely, therefore, that the altered contractile characteristics of mdx muscle were a result of the presence of damaged but otherwise normal fibres. 6. C57 and mdx tibialis anterior muscles displayed similar degrees of force loss after exercise. Furthermore, the rate of recovery after the nadir of force loss was very similar for the two groups. By 12 days after exercise, force recovered to 76% and 80% of control in C57 and mdx muscles, respectively. Our findings do not support the hypothesis that dystrophin deficient muscle is more susceptible to exercise-induced muscle damage. PMID- 1311661 TI - Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man. AB - 1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h-1 kg-1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 +/- 0.20 versus 0.67 +/- 0.10 mmol/l), plasma nonesterified fatty acid (395 +/- 13 versus 51 +/- 1 mumol/l), blood glycerol (152 +/- 2 versus 11 +/- 1 mumol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64 104) versus 4 (3-5) mumol/l] were all significantly higher (all P less than 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 +/- 0.07 versus 0.27 +/- 0.08 mg min-1 kg-1, P less than 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 +/- 0.77 to 6.17 +/- 0.71 mg min-1 kg-1, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311663 TI - Granulocyte margination in the human lung and its response to strenuous exercise. AB - 1. It is widely believed that the lung is an important site of granulocyte margination and releases most of the granulocytes of the peripheral neutrophilia of exercise. 2. We measured granulocyte margination in the lung in terms of the lung total blood granulocyte pool and the lung circulating granulocyte pool in eight patients without inflammatory disease or evidence of lung pathology by comparing the regional gamma-camera lung count rate of 111In-labelled granulocytes with that of 111In-labelled erythrocytes. According to the respective 111In activities in peripheral blood samples taken between 5 and 40 min after granulocyte injection, the lung marginating granulocyte pool was 0.78 (SEM 0.045) of the lung total blood granulocyte pool or 4.6 (0.92) of the lung circulating granulocyte pool 5 min after injection, decreasing to plateau values of 0.57 (0.053) and 1.53 (0.28) from 20 min after injection. This compared with corresponding whole-body ratios of about 0.6 and 1.5, respectively. 3. After 4 min of maximal exercise in four normal subjects given 111In-labelled granulocytes 60 min before exercise, the 111In-labelled granulocyte count rate over the lung increased to 1.23 (0.05) of the pre-exercise value with a time course that was essentially identical with the time course of the peripheral native neutrophilia. The spleen 111In signal decreased with the same time course, reaching a minimum of 0.63 (0.05) of the pre-exercise level at 5-10 min after the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311664 TI - Lactic acidosis treated with continuous hemodiafiltration and regional citrate anticoagulation. AB - OBJECTIVE: To evaluate the effectiveness of continuous arteriovenous hemodiafiltration (CAVHD) using citrate as the anticoagulant for the treatment of lactic acidosis in patients with renal failure. DESIGN: Case series with careful monitoring of the clinical course of patients being treated in a medical or surgical ICU. SETTING: University hospital ICU. PATIENTS: Two patients with lactic acidosis are described, along with our experience using CAVHD and citrate in other clinical settings. INTERVENTIONS: CAVHD was used to manage renal failure, while a continuous infusion of citrate was administered to maintain patency of the extracorporeal circuit. MEASUREMENTS: Total and ionized serum calcium concentrations and citrate concentrations were monitored. MAIN RESULTS: CAVHD with citrate as the anticoagulant proved to be a convenient means of managing vascular volume, serum electrolyte concentrations, acid-base balance, and replacement renal function requirements in the setting of severe lactic acidosis, oliguric renal failure, and hemorrhagic diathesis. CONCLUSIONS: CAVHD with citrate as the anticoagulant can be recommended as effective therapy for selected patients, but careful monitoring is needed to avoid serious complications. PMID- 1311665 TI - Cystic mucinous adenocarcinoma of the lung. Two cases of cystic variant of mucus producing lung adenocarcinoma. AB - Two previously unreported cases of mucus-producing lung adenocarcinoma are presented as uncommon tumors, which are clinicopathologically different from other histologic types of lung adenocarcinoma. The tumors, showing apparently rapid development on chest roentgenograms, were tightly packed with copious mucus and resembled cystic lesions. Because they contained very few cancer cells, and these were only at the periphery, it was impossible to diagnose malignant neoplasms preoperatively through cytologic examination. The present tumors, which we described as cystic mucinous adenocarcinoma, are considered to be a cystic variant of mucus-producing lung adenocarcinoma that expands grossly by storing mucus. PMID- 1311666 TI - Effects of the addition of nedocromil sodium to maintenance bronchodilator therapy in the management of chronic asthma. AB - STUDY OBJECTIVES: To assess the efficacy and safety of nedocromil sodium metered dose aerosol as an adjunct to sustained-released theophylline therapy in adult theophylline-dependent asthma patients and to examine the ability of nedocromil sodium to substitute for theophylline. DESIGN: Randomized double-blind placebo controlled parallel group study. Two-week baseline, eight-week treatment period. SETTING: Out-Patient Clinic. PATIENTS: Sequential sample of 35 adult chronic asthmatic patients maintained on a regimen of sustained-release theophylline (dose range, 400 to 800 mg daily) and on-demand inhaled beta 2-bronchodilators. All patients completed the study. INTERVENTIONS: 2 x 2-mg nedocromil sodium metered dose aerosol twice daily or matching placebo randomly allocated after two week baseline. Theophylline dose reduced by half or one third after four weeks of test treatments, then stopped for final two weeks. Use of inhaled beta 2 bronchodilators permitted throughout trial period. MEASUREMENTS AND RESULTS: The following results were in favor (statistically significant findings, p less than 0.05) of nedocromil sodium compared with placebo: all diary card efficacy variables (nighttime asthma, morning tightness, daytime asthma, cough, twice daily peak expiratory flow [PEF], inhaled beta 2 use) during all periods of assessment (weeks 1 to 2, 3 to 4, 5 to 6, and 7 to 8) with the exception of cough and nighttime beta 2 use during weeks 1 to 2; patient and clinician opinion of treatment efficacy (end of weeks 4 and 8); ability to reduce the theophylline dose; clinician assessment of asthma severity at the end of the study, and clinic FEV1 at weeks 4, 5, 6, and 8. One placebo-treated patient reported transient moderately severe nausea and taste loss. No clinically significant changes were seen in the laboratory data. CONCLUSION: Nedocromil sodium, 4 mg twice daily, conferred significant benefit when added to sustained-release theophylline therapy. The results suggest that nedocromil sodium may permit a reduction in theophylline dosage and possibly substitute for theophylline in previously dependent patients. PMID- 1311667 TI - Resection of pulmonary metastasis to the azygous lobe from a malignant fibrous histiocytoma. AB - A 55-year-old man developed a pulmonary metastasis to the azygous lobe from a malignant fibrous histiocytoma of the thigh. The azygous lobe was not identified at the initial resection. A simple technique for the identification and mobilization of the azygous lobe is presented. Preoperative identification of this anatomic variant may assist in resection of parenchymal neoplasms. PMID- 1311668 TI - Expression of the potent inflammatory cytokines, GM-CSF, IL6, and IL8, in bronchial epithelial cells of asthmatic patients. PMID- 1311669 TI - Mechanisms for regulating the cell surface distribution of Na/K-ATPase in polarized epithelial cells. PMID- 1311670 TI - Regulation of ciliary beat frequency in respiratory tract cells. PMID- 1311671 TI - The effects of amylin on insulin secretion from Rin m5F cells and glycogen synthesis and lipogenesis in rat primary cultured hepatocytes. AB - The purpose of the study was to determine the physiological actions of amylin, a novel 37-amino acid peptide isolated from pancreatic islet amyloid deposits. Our results showed that an infusion of amylin reduced fasting plasma insulin levels and impaired glucose tolerance in mice. Amylin significantly reduced insulin secretion in rat insulinoma cell lines (Rin m5F cells) that were stimulated by either isoproterenol and forskolin, but it did not affect insulin secretion stimulated by isobutyl-methylxanthine (IBMX) or dibutyryl cyclic-adenosine monophosphate (db-cAMP). Amylin also reduced cAMP levels in Rin m5F cells in response to isoproterenol, but did not affect cAMP levels in cells pretreated with pertussis toxin. These results suggest that the reduction of cAMP by amylin may be mediated through pertussis toxin-sensitive Gi proteins. Amylin significantly reduced basal and insulin-stimulated glycogen synthesis in rat primary cultured hepatocytes. Amylin stimulated basal and insulin-stimulated lipogenesis in hepatocytes. Amylin did not affect DNA synthesis in hepatocytes. These results suggest that amylin conducts dispersion actions on in vivo glucose metabolism in rat, and in vitro insulin secretion from Rin m5F cells and metabolism in rat hepatocytes. PMID- 1311672 TI - Polyphasic motor unit action potentials in early radiculopathy: their presence and ephaptic transmission as an hypothesis. AB - Various investigators have reported the presence of polyphasic motor unit potentials in radiculopathy. Some of these potentials have been shown to occur the first few weeks after the onset of symptoms, before reinnervation has begun. We hypothesize that the polyphasic motor unit potential described in acute nerve root compression can be the result of ephaptic transmission between adjacent nerve axons in the region of the inflamed root. The historical, clinical and experimental evidence supporting this hypothesis is presented. PMID- 1311673 TI - Transmission times from cutaneous and mixed nerves of lower limbs. AB - In each of 10 normal subjects, P28 and N31 far-field components as well as the cortical N37 and P40 waves were identified for both Sural (SN) and Posterior Tibial nerve (PTN) stimulation at the ankle. Peripheral conduction velocity along the popliteal fossa-L3 segment and spinal transmission velocity over the L3-Cv2 segment did not differ significantly for the two nerves. The average latencies of N37 and P40 to stimulation of PTN were 2.55 and 3.65 msec shorter than corresponding latencies from SN. If we consider the P28-N37 and P28-P40 intervals as central transmission times, only the former approaches upper limb CCT values closely enough to support the analogy between median nerve N20 and PTN N37. At the intracranial level, the P28-N37 inter-peak latency was significantly shorter for PTN than SN. The P28 component is generally attributed to lemniscal activity. Thus, the discrepancy in afferent transmission times from the leg's mixed and sensory nerves would appear to take place at a level that is supralemniscal but subcortical. PMID- 1311674 TI - Nitrobenzo[a]pyrene-induced DNA amplification in SV40-transformed Chinese hamster embryo cells. AB - Nitrobenzo[a]pyrenes (NBaPs) are ubiquitous environmental pollutants that produce mutations in Salmonella typhimurium and Chinese hamster ovary cells. In this study, 1-, 3-, and 6-NBaP induced amplification of SV40 DNA sequences in an SV40 transformed Chinese hamster embryo cell line which is sensitive to DNA amplification by various known carcinogens. Of the three isomers, 3-NBaP produced the highest level of gene amplification, which was 4.8 relative to untreated controls at a dose of 5 micrograms/ml. Considering the relationship between gene amplification and tumorigenesis, it seems prudent to carry out a more exhaustive analysis of the carcinogenic potential of these agents. PMID- 1311675 TI - The axonally secreted cell adhesion molecule, axonin-1. Primary structure, immunoglobulin-like and fibronectin-type-III-like domains and glycosyl phosphatidylinositol anchorage. AB - Axonin-1 is an axon-associated cell adhesion molecule (AxCAM) of the chicken, which promotes neurite outgrowth by interaction with the AxCAM L1(G4) of the neuritic membrane. Here we report the cloning and sequence determination of a cDNA encoding axonin-1. Peptides generated by enzymatic cleavage showed similarity to the AxCAM F11. Degenerated polymerase chain reaction (PCR) primers were designed and an axonin-1 fragment was amplified from mRNA of embryonic retina. Screening of a cDNA library from embryonic brain resulted in the isolation of a 4.0-kb cDNA insert with an open reading frame of 3108 nucleotides. The deduced polypeptide of 1036 amino acids includes a putative hydrophobic N terminal signal sequence of 23 or 25 amino acids and a C-terminal hydrophobic sequence of 29 amino acids which is suggestive of sequences serving as signal for the attachment of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) anchor. The putative mature form of axonin-1 comprises six immunoglobulin-like repeats, followed by four fibronectin-type III repeats. Axonin-1 exhibits 75% amino acid identity with the AxCAM TAG-1 of the rat, suggesting that it is the chicken homologue of TAG-1. Like TAG-1, axonin-1 is glycosyl-PtdIns-anchored to the neuronal membrane; in contrast to TAG-1, it does not exhibit an Arg-Gly-Asp sequence. PMID- 1311676 TI - Total synthesis of horse heart apocytochrome c by conformation-assisted condensation of two chemically synthesized fragments. AB - A fully synthetic peptide, corresponding to the entire 104-residue sequence of horse heart apocytochrome c with Met65 replaced by homoserine, has been obtained by an original conformation-assisted three-fragment condensation procedure. The method involves the selective joining of two synthetic fragments, namely residues 1-65 of the apopeptide with Met65 replaced by homoserine lactone and residues 66 104 of the protein in the presence of fragment 1-25 of the native heme-containing peptide. The joining conditions have been optimized with regard to solvent, pH and possible influence of additives. The presence of radical scavengers and the complete exclusion of oxygen were found essential in order to prevent oxidative side reactions. A sensitive method based on reverse-phase HPLC has been used to monitor the course of the reaction. Condensation yields up to 80% were obtained. The data obtained by this new three-fragment rejoining approach are discussed and compared to those of a similar two-fragment condensation procedure. Our data demonstrate how the folding properties of large synthetic peptide fragments, organized in a complex, can be utilized to extend the presently improved solid phase peptide methods to the synthesis of a functioning protein with more than 100 residues. PMID- 1311677 TI - Structural diversity among sulfated alpha-L-galactans from ascidians (tunicates). Studies on the species Ciona intestinalis and Herdmania monus. AB - Sulfated polysaccharides occurring in the tunic of different species of ascidians differ markedly in electrophoretic pattern and chemical composition. A purified sulfated alpha-L-galactan from Herdmania monus was studied using methylation analysis and NMR spectroscopy; it is composed mainly of 3-sulfated 4-linked alpha L-galactopyranoyl units. This is the first description of a homo-polymer of sulfated alpha-L-galactose. In contrast, the sulfated L-galactan from Ciona intestinalis shows marked structural heterogeneity and a low sulfate content. These data indicate unusual structural diversity among sulfated L-galactans from different species of ascidians. PMID- 1311678 TI - Identification and molecular characterization of the calmodulin-binding subunit gene (CMP1) of protein phosphatase 2B from Saccharomyces cerevisiae. An alpha factor inducible gene. AB - A method has been developed for the rapid purification of yeast calmodulin in high yield. Using a 125I-labeled calmodulin SDS/PAGE gel overlay procedure with either yeast or bovine calmodulin, we show that the bovine and yeast proteins recognize the same proteins in total yeast extracts. However, yeast calmodulin does not bind to many of the proteins in vertebrate cells identified using bovine calmodulin. A lambda gt11 yeast genomic expression library was screened with yeast or bovine brain 125I-calmodulin to identify sequences derived from calmodulin binding proteins. Twelve clones were recovered, all containing a common DNA insert; all bound calmodulin in a Ca(2+)-dependent manner. The complete coding sequence was recovered and sequenced. The predicted protein sequence show greater than 50% identity to the A subunit of vertebrate protein phosphatase 2B. The gene was designated CMP1 and shown to reside on chromosome IV. Disruption or over-expression of CMP1 have no obvious phenotype; yeast appears to contain one or more CMP1-related genes. The protein product of the CMP1 gene is elevated by alpha-factor treatment, suggesting an involvement of protein phosphatase 2B in the mating response. PMID- 1311679 TI - Mossbauer study of the native, reduced and substrate-reacted Desulfovibrio gigas aldehyde oxido-reductase. AB - The Desulfovibrio gigas aldehyde-oxido-reductase contains molybdenum and iron sulfur clusters. Mossbauer spectroscopy was used to characterize the iron-sulfur clusters. Spectra of the enzyme in its oxidized, partially reduced and benzaldehyde-reacted states were recorded at different temperatures and applied magnetic fields. All the iron atoms in D. gigas aldehyde oxido-reductase are organized as [2Fe-2S] clusters. In the oxidized enzyme, the clusters are diamagnetic and exhibit a single quadrupole doublet with parameters (delta EQ = 0.62 +/- 0.02 mm/s and delta = 0.27 +/- 0.01 mm/s) typical for the [2Fe-2S]2+ state. Mossbauer spectra of the reduced clusters also show the characteristics of a [2Fe-2S]1+ cluster and can be explained by a spin-coupling model proposed for the [2Fe-2S] cluster where a high-spin ferrous ion (S = 2) is antiferromagnetically coupled to a high-spin ferric ion (S = 5/2) to form a S = 1/2 system. Two ferrous sites with different delta EQ values (3.42 mm/s and 2.93 mm/s at 85 K) are observed for the reduced enzyme, indicating the presence of two types of [2Fe-2S] clusters in the D. gigas enzyme. Taking this observation together with the re-evaluated value of iron content (3.5 +/- 0.1 Fe/molecule), it is concluded that, similar to other Mo-hydroxylases, the D. gigas aldehyde oxido-reductase also contains two spectroscopically distinguishable [2Fe-2S] clusters. PMID- 1311680 TI - Mossbauer characterization of the tetraheme cytochrome c3 from Desulfovibrio baculatus (DSM 1743). Spectral deconvolution of the heme components. AB - Mossbauer spectroscopy was used to study the tetraheme cytochrome c3 from Desulfovibrio baculatus (DSM 1743). Samples with different degrees of reduction were prepared using a redoxtitration technique. In the reduced cytochrome c3, all four hemes are reduced and exhibit diamagnetic Mossbauer spectra typical for low spin ferrous hemes (S = 0). In the oxidized protein, the hemes are low-spin ferric (S = 1/2) and exhibit overlapping magnetic Mossbauer spectra. A method of differential spectroscopy was applied to deconvolute the four overlapping heme spectra and a crystal-field model was used for data analysis. Characteristic Mossbauer spectral components for each heme group are obtained. Hyperfine and crystal-field parameters for all four hemes are determined from these deconvoluted spectra. PMID- 1311681 TI - Regulatory phosphorylation of Sorghum leaf phosphoenolpyruvate carboxylase. Identification of the protein-serine kinase and some elements of the signal transduction cascade. AB - The phosphoenolpyruvate (PPrv) carboxylase isozyme involved in C4 photosynthesis undergoes a day/night reversible phosphorylation process in leaves of the C4 plant, Sorghum. Ser8 of the target enzyme oscillates between a high (light) and a low (dark) phosphorylation status. Both in vivo and in vitro, phosphorylation of dark-form carboxylase was accompanied by an increase in the apparent Ki of the feedback inhibitor L-malate and an increase in Vmax. Feeding detached leaves various photosynthetic inhibitors, i.e. 3-(3,4-dichlorophenyl)-1,1-dimethylurea, gramicidin and DL-glyceraldehyde, prevented PPrv carboxylase phosphorylation in the light, thus suggesting that the cascade involves the photosynthetic apparatus as the light signal receptor, and presumably has the electron transfer chain and the Calvin-Benson cycle as components in the signal-transduction chain. Two protein-serine kinases capable of phosphorylating PPrv carboxylase in vitro have been partially purified from light-adapted leaves. One was isolated on a calmodulin-Sepharose column; it was calcium-dependent but did not require calmodulin for activity. The other was purified on a blue-dextran-agarose column and the only Me2+ required for activity was Mg2+. In reconstituted phosphorylation assays, only the latter caused the expected decrease in malate sensitivity of PPrv carboxylase suggesting that this protein is the genuine PPrv carboxylase-kinase. Desalted extracts from light-adapted leaves possessed a considerably greater phosphorylation capacity with immunopurified dephosphorylated PPrv carboxylase as substrate than did dark extracts. This light stimulation was insensitive to type 2A protein phosphatase inhibitors, okadaic acid and microcystin-LR, which suggests that the kinase is a controlled step in the cascade which leads to phosphorylation of PPrv carboxylase. The higher phosphorylation capacity of light-adapted leaf tissue was nullified by pretreatment with the cytosolic protein synthesis inhibitor, cycloheximide. Thus, protein turnover is involved as part of the mechanism controlling the activity of the kinase purified on blue-dextran-agarose. However, no information is available with respect to the specific nature of the link between the above-mentioned light transducing steps and the protein kinase that achieves the physiological response. Finally, the in vivo phosphorylation site (Ser8) in the N-terminal region of the C4 type Sorghum PPrv carboxylase is also present in a non photosynthetic form of the Sorghum enzyme (Ser7), as deduced by cDNA sequence analysis. PMID- 1311682 TI - Bilayer-penetrating properties enable apocytochrome c to follow a special import pathway into mitochondria. AB - In this study, we have investigated the protein/lipid interactions of two mitochondrial precursor proteins, apocytochrome c and pCOX IV-DHFR, which exhibit mitochondrial import pathways with different characteristics. In-vitro synthesized apocytochrome c was found to bind efficiently and specifically to liposomes composed of negatively charged phospholipids and showed a (at least partial) translocation across a lipid bilayer, as reported previously for the chemically prepared precursor protein [Rietveld, A. & de Kruijff, B. (1984) J. Biol. Chem. 259, 6704-6707; Dumont, M. E. & Richards, F. M. (1984) J. Biol. Chem. 259, 4147-4156]. Negatively charged liposomes were shown to efficiently compete with mitochondria for import of in-vitro-synthesized apocytochrome c into the organelle, suggesting an important role for negatively charged phospholipids in the initial binding of apocytochrome c to mitochondria. In contrast, the purified and in-vitro-synthesized precursor fusion protein pCOX IV-DHFR, consisting of the presequence of yeast cytochrome oxidase subunit IV fused to mouse dihydrofolate reductase was unable to translocate across a pure lipid bilayer. The data indicate that the ability of apocytochrome c to spontaneously translocate across the bilayer is not shared by all mitochondrial precursor proteins. The implications of the special protein/lipid interaction of apocytochrome c for import into mitochondria will be discussed. PMID- 1311683 TI - Characterization of hepatocyte-growth-factor receptors on Meth A cells. AB - Hepatocyte growth factor (HGF) is a heparin-binding polypeptide mitogen for a variety of cell types including hepatocytes. HGF also has cytotoxic activity on some tumor cell lines as well as scattering activity on epithelial cells. In this study, recombinant human HGF was used to identify HGF-binding cell surface receptors on Meth A cells, whose growth is inhibited by HGF. Scatchard analysis of binding data indicated that there were two classes of binding sites with high affinity (Kd = 17 pM) and low affinity (Kd = 6.7 nM) and the average numbers were 6600 and 2,600,000 per cell, respectively. Affinity cross-linking of 125I-HGF to Meth A cells resulted in a major and a minor specifically labeled complex. Competition analysis followed by cross-linking indicated that the HGF-binding proteins were involved in the formation of the high-affinity binding. The existence of the two HGF-binding surface proteins was confirmed by HGF-dependent immunoprecipitation of the binding proteins with an anti-HGF polyclonal antibody. The molecular masses of the major and the minor surface proteins were 160 kDa and 130 kDa, respectively. The 160-kDa protein was autophosphorylated in vitro on tyrosine residue and was immunoprecipitated with an antiserum against the c-met proto-oncogene product. These results indicate that the 160-kDa HGF-binding surface protein on Meth A cells is the c-met protein. Furthermore, tyrosine phosphorylation of the c-met protein was stimulated by HGF treatment of Meth A cells, suggesting that it may be involved in the signal transduction of the growth inhibition of Meth A cells by HGF. PMID- 1311684 TI - Identification of two domains which mediate the binding of activating phospholipids to the plasma-membrane Ca2+ pump. AB - The stimulation of the purified human erythrocyte calcium pump by acidic phospholipids was investigated using synthetic peptides corresponding to a putative phospholipid-responsive domain [Zvaritch, E., James, P., Vorherr, T., Falchetto, R., Modyanov, N. & Carafoli, E. (1990) Biochemistry 29, 8070-8076] and to the calmodulin-binding domain of the pump. The peptides interfered with the activation of the enzyme by phosphatidylserine and phosphatidic acid in competition assays. The peptide corresponding to the calmodulin-binding domain was found to be the most efficient antagonist. Direct binding measurements using fluorescent derivatives of the peptides confirmed the interaction between the acidic phospholipids and the peptides, and fluorescence titrations of dansylated calmodulin with the purified ATPase showed a direct effect of acidic phospholipids on calmodulin binding. A proteolyzed preparation of the Ca(2+) ATPase lacking the calmodulin-binding domain confirmed that the phospholipid induced stimulation is mediated by two sites, one located in the C-terminal portion of the previously identified 44-amino-acid phospholipid-responsive domain, the other in the calmodulin-binding domain. PMID- 1311685 TI - Pharmacokinetics of rufloxacin in healthy volunteers. AB - The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 micrograms.h.ml-1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p.o. was 715 micrograms.h.ml-1 in fasting subjects and 614 micrograms.h.ml-1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30-40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33-36 h and 50-80 h, respectively). PMID- 1311686 TI - Effects of Ro 5-4864 and PK 11195 in rat duodenum and vas deferens. AB - Ro 5-4864 and PK 11195 inhibit in a concentration-dependent manner carbachol induced contractions in rat duodenum (IC50: 1.56 +/- 0.07 x 10(-5) M and 1.18 +/- 0.07 x 10(-5) M respectively). The antagonism is non-competitive and is not mediated by peripheral-type benzodiazepine receptors. The Ro 5-4864 effect is modulated by the calcium concentration of the Tyrode-Ringer solution. In the presence of 1 mM NaF/10 microM AlCl3, Ro 5-4864 and PK 11195 do not inhibit carbachol-induced contractions. Moreover, Ro 5-4864 and PK 11195 significantly relax AlF(4-)-induced contractions, with IC50 values of 2.01 +/- 0.12 x 10(-5) M and 1.28 +/- 0.11 x 10(-5) M respectively. This effect is also modulated by the calcium concentration of the medium. Pertussis toxin potentiates the antagonist effects of Ro 5-4864 and PK 11195 on carbachol-induced contractions, but cholera toxin does not affect them. Ro 5-4864 and PK 11195 inhibit 45Ca2+ uptake induced by KCl (120 mM) in rat vas deferens, but do not affect either basal 45Ca efflux or noradrenaline-induced 45Ca2+ efflux. Only high doses of PK 11195 (above 5 x 10(-5) M) are able to produce a slight reduction of the accumulation of inositol phosphates induced by methoxamine in rat vas deferens, while Ro 5-4864 has no significant effect. Finally, Ro 5-4864 and PK 11195 reduce calcium influx, but do not seem to be the only mechanism of the antagonistic effect on carbachol-induced contractions. An alteration of other second messengers, probably cyclic monophosphate nucleotides, may be involved. PMID- 1311687 TI - 5-HT1C receptors mediate phosphoinositide turnover activation in the immature rat hippocampus. AB - The activation of phosphoinositide turnover in rat cerebral cortex and choroid plexus is triggered by the stimulation of 5-HT2 and 5-HT1C receptors, respectively. To characterize the 5-HT receptor subtype mediating the activation of phosphoinositide turnover in the hippocampus, the potency of several 5-HT agonists and antagonists on total [3H]inositol phosphate formation has been compared in the hippocampus, cerebral cortex and choroid plexus of immature rats. 5-HT, alpha-methyl-5-HT, quipazine, MK-212, mCPP (m-chlorophenylpiperazine) and TFMPP (m-trifluoromethylphenylpiperazine) are less potent and efficient in stimulating phosphoinositide turnover in the hippocampus and cerebral cortex than in the choroid plexus. However, for a number of 5-HT receptor antagonists (ketanserin, spiperone, ritanserin, pizotifen, cyproheptadine, mesulergine, mianserin, methiothepin, methysergide) there is a good correlation (r = 0.82) between their antagonistic potency in the hippocampus and choroid plexus while such correlation is not observed for the hippocampus and cerebral cortex. The specific 5-HT2 receptor antagonist spiperone only partially antagonizes (37% inhibition at 1 microM) the stimulation by 5-HT of phosphoinositide turnover in the hippocampus. These results suggest that in the immature rat hippocampus the activation of phosphoinositide turnover by 5-HT is mainly mediated by the 5-HT1C receptor subtype. PMID- 1311688 TI - Is the bradykinin-induced Ca2+ influx and the formation of endothelium-derived relaxing factor mediated by a G protein? AB - In cultured porcine aortic endothelial cells bradykinin produced a long-lasting Ca2+ influx. In contrast to the G protein-independent Ca2+ entry evoked by ionomycin or digitonin, bradykinin-induced Ca2+ influx was antagonized by Ni2+ with an IC50 value of about 50 microM. Since identical IC50 values for Ni2+ were found when Ca2+ entry was induced by sodium fluoride or GTP gamma S, we suggest that stimulation of G protein(s) results in the activation of the same Ca2+ channels as stimulation by bradykinin. This conclusion is supported by our findings that inhibition of GTPase by mepacrine amplified bradykinin-stimulated Ca2+ influx, but did not interfere with the effect of the Ca2+ ionophore A23187. Similar to its effect on Ca2+ influx, mepacrine also potentiated endothelium derived relaxing factor (EDRF) formation by bradykinin and sodium fluoride, but did not affect A23187-induced EDRF biosynthesis. We therefore suggest that in endothelial cells the bradykinin-induced Ca2+ influx and the resulting formation of EDRF are regulated by a G protein. PMID- 1311689 TI - Inhibition of a dihydropyridine, omega-conotoxin insensitive Ca2+ channel in rat synaptosomes by venom of the spider Hololena curta. AB - Inhibition of the N and L type Ca2+ channels with omega conotoxin GVIA (omega CgTx) together with the dihydropyridine (-)-202-791 produces slight reduction (congruent to 25%) of K(+)-evoked Ca2+ influx in mammalian synaptosomes. These results and others suggest the existence of a third high threshold voltage sensitive calcium channel (VSCC) responsible for the majority of influx. Venom from the funnel web spider Hololena curta potently and persistently inhibited Ca2+ influx in rat cortical synaptosomes (IC50 1:10,000 or 4.21 micrograms/venom protein/ml of synaptosomes). Also Ca2+ influx in cerebellar synaptosomes was inhibited in a similar manner. K(+)-evoked tritium release from synaptosomes labeled with [3H]noradrenaline was inhibited by Hololena venom (congruent to 60% reduction at 10 micrograms/venom protein). Inhibition of Ca2+ influx by venom was unaffected by combined omega-CgTx and (-)-202-791 pretreatment (both 1 microM). Hololena venom and its active constituent should provide useful tools to investigate the role of this novel Ca2+ channel in neuronal function. PMID- 1311690 TI - High affinity ligands for 'diazepam-insensitive' benzodiazepine receptors. AB - Structurally diverse compounds have been shown to possess high affinities for benzodiazepine receptors in their 'diazepam-sensitive' (DS) conformations. In contrast, only the imidazobenzodiazepinone Ro 15-4513 has been shown to exhibit a high affinity for the 'diazepam-insensitive' (DI) conformation of benzodiazepine receptors. We examined a series of 1,4-diazepines containing one or more annelated ring systems for their affinities at DI and DS benzodiazepine receptors, several 1,4-diazepinone carboxylates including Ro 19-4603, Ro 16-6028 and Ro 15-3505 were found to possess high affinities (Ki approximately 2.6-20 nM) for DI. Nonetheless, among the ligands examined, Ro 15-4513 was the only substance with a DI/DS potency ratio approximately 1; other substances had ratios ranging from 13 to greater than 1000. Ligands with high to moderate affinities at DI were previously classified as partial agonists, antagonists, or partial inverse agonists at DS benzodiazepine receptors, but behaved as 'GABA neutral' (antagonist) substances at DI. The identification of several additional high affinity ligands at DI benzodiazepine receptors may be helpful in elucidating the pharmacological and physiological importance of these sites. PMID- 1311691 TI - Subcellular distribution of (+)-[3H]SKF 10,047 binding sites in rat liver. AB - The distribution of (+)-[3H]SKF 10,047 binding sites and the distribution of the established plasma membrane, nuclear, mitochondrial and endoplasmic reticulum markers in subcellular fractions of rat liver have been studied. The distribution profile of (+)-[3H]SKF 10,047 binding sites coincided with that of NADPH cytochrome c reductase, the endoplasmic reticulum marker. (+)-[3H]SKF 10,047 binding sites in rat liver are therefore suggested to be located on the endoplasmic reticulum membrane and to represent a membrane-bound enzyme. PMID- 1311692 TI - Effects of three distinct natriuretic peptides on receptor binding and guanylate cyclase activities in rat glioma cells. AB - Receptor binding and cyclic GMP generation by three distinct natriuretic peptides (ANP, BNP, CNP) were studied in a cultured rat glioma cell line (C6). Binding studies revealed the presence of high-affinity binding sites for three natriuretic peptides with almost comparable affinities. In contrast, CNP and BNP were almost equipotent in stimulating intracellular cyclic GMP generation over the low concentration range, but CNP caused further elevation in the high concentration range, whereas ANP was minimally effective. Our data suggest that the glioma cells possess receptors more responsive to CNP than ANP and BNP despite no apparent correlation between receptor binding affinities and cyclic GMP responses. PMID- 1311694 TI - Genetic changes accompanying increased fitness in evolving populations of Escherichia coli. AB - Two populations of Escherichia coli, each initiated with a single clone containing a derivative of the plasmid pBR322, were maintained for long periods in glucose-limited continuous culture. In both populations, after an extensive number of generations had elapsed, clones were isolated in which the transposon Tn3 from the plasmid had integrated into the bacterial chromosome. In both cases examined, the transpositions were shown to increase relative fitness approximately 6-7%, in the environment in which the populations were maintained. The loci of integration were mapped to approximately 13.2 min (population 1) and approximately 32.8 min (population 2). PMID- 1311693 TI - Mumps virus infects beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules. AB - The ability of mumps virus to infect pancreatic Beta cells and cause alterations in their HLA expression was evaluated in cultured human fetal islet cell clusters. Mumps virus could be isolated during the whole culture period (6-8 days) and 60% of cells, including Beta cells, contained viral nucleocapsid protein at the end of the culturing. A minor decrease in insulin secretion was observed in some of the infected cultures. The infection was invariably associated with an increase in the expression of HLA class I molecules. This enhancement was mediated by soluble factors secreted by infected cells. The infection could not induce the expression of HLA-DR molecules. However, external interferon-gamma was able to cause a clear rise in DR-expression which was observed only on non-Beta-cells. Rubella and coxsackie B4 viruses were also able to enhance the expression of class I molecules while herpes simplex virus type 2 was not. The results suggest that certain viruses are able to infect Beta cells and cause alterations in their immunological appearance. Increased HLA class I expression in infected islets may exaggerate the autoimmune process in pre diabetic individuals by increasing the activity of autoreactive cytotoxic T cells. PMID- 1311695 TI - Elimination of the yeast RAD6 ubiquitin conjugase enhances base-pair transitions and G.C----T.A transversions as well as transposition of the Ty element: implications for the control of spontaneous mutation. AB - The RAD6 gene of the yeast Saccharomyces cerevisiae encodes an enzyme that conjugates ubiquitin to other proteins. Defects in RAD6 confer a mutator phenotype due, in part, to an increased rate of transposition of the yeast Ty element. To further delineate the role of protein ubiquitination in the control of spontaneous mutagenesis in yeast, we have characterized 202 mutations that arose spontaneously in the SUP4-o gene carried on a centromere vector in a RAD6 deletion strain. The resulting mutational spectrum was compared to that for 354 spontaneous SUP4-o mutations isolated in the isogenic wild-type parent. This comparison revealed that the rad6 mutator enhanced the rate of single base-pair substitution, as well as Ty insertion, but did not affect the rates of the other mutational classes detected. Relative to the wild-type parent, Ty inserted at considerably more SUP4-o positions in the rad6 strain with a significantly smaller fraction detected at a transposition hotspot. These findings suggest that, in addition to the rate of transposition, protein ubiquitination might influence the target site specificity of Ty insertion. The increase in the substitution rate accounted for approximately 90% of the rad6 mutator effect but only the two transitions and the G. C----T.A transversion were enhanced. Analysis of the distribution of these events within SUP4-o suggested that the site specificity of the substitutions was influenced by DNA sequence context. Transformation of heteroduplex plasmid DNAs into the two strains demonstrated that the rad6 mutator did not reduce the efficiency of correcting mismatches that could give rise to the transitions or transversion nor did it bias restoration of the mismatches to the incorrect base-pairs. These results are discussed in relation to possible mechanisms that might link ubiquitination of proteins to spontaneous mutation rates. PMID- 1311696 TI - Genetic interactions among Chlamydomonas reinhardtii mutations that confer resistance to anti-microtubule herbicides. AB - We previously described two types of genetic interactions among recessive mutations in the APM1 and APM2 loci of Chlamydomonas reinhardtii that may reflect a physical association of the gene products or their involvement in a common structure/process: (1) allele-specific synthetic lethality, and (2) unlinked noncomplementation, or dominant enhancement. To further investigate these interactions, we isolated revertants in which the heat sensitivity caused by the apm2-1 mutation is lost. The heat-insensitive revertants were either fully or partially suppressed for the drug-resistance caused by the apm2-1 allele. In recombination tests the revertants behaved as if the suppressing mutation mapped within the APM2 locus; the partial suppressors of apm2-1 herbicide resistance failed to complement apm2-1, leading to the conclusion that they were likely to be intragenic pseudorevertants. The apm2-1 partial suppressor mutations reversed apm1-apm2-1 synthetic lethality in an allele-specific manner with respect both to apm1- alleles and apm2-1 suppressor mutations. Those apm1- apm2-1rev strains that regained viability also regained heat sensitivity characteristic of the original apm2-1 mutation, even though the apm2-1 suppressor strains were fully heat insensitive. The Hs+ phenotypes of apm2-1 partial suppressors were also reversed by treatment with the microtubule-stabilizing agent deuterium oxide (D2O). In addition to the above interactions, we observed interallelic complementation and phenotypic enhancement of temperature conditionality among apm1- alleles. Evidence of a role for the products of the two genes in microtubule-based processes was obtained from studying flagellar assembly in apm1- and apm2- mutants. PMID- 1311698 TI - The molecular through ecological genetics of abnormal abdomen. IV. Components of genetic variation in a natural population of Drosophila mercatorum. AB - Natural populations of Drosophila mercatorum are polymorphic for a phenotypic syndrome known as abnormal abdomen (aa). This syndrome is characterized by a slow down in egg-to-adult developmental time, retention of juvenile abdominal cuticle in the adult, increased early female fecundity, and decreased adult longevity. Previous studies revealed that the expression of this syndrome in females is controlled by two closely linked X chromosomal elements: the occurrence of an R1 insert in a third or more of the X-linked 28S ribosomal genes (rDNA), and the failure of replicative selection favoring uninserted 28S genes in larval polytene tissues. The expression of this syndrome in males in a laboratory stock was associated with the deletion of the rDNA normally found on the Y chromosome. In this paper we quantify the levels of genetic variation for these three components in a natural population of Drosophila mercatorum found near Kamuela, Hawaii. Extensive variation is found in the natural population for both of the X-linked components. Moreover, there is a significant association between variation in the proportion of R1 inserted 28S genes with allelic variation at the underreplication (ur) locus such that both of the necessary components for aa expression in females tend to cosegregate in the natural population. Accordingly, these two closely linked X chromosomal elements are behaving as a supergene in the natural population. Because of this association, we do not believe the R1 insert to be actively transposing to an appreciable extent. The Y chromosomes extracted from nature are also polymorphic, with 16% of the Ys lacking the Y specific rDNA marker. The absence of this marker is significantly associated with the expression of aa in males. Hence, all three of the major genetic determinants of the abnormal abdomen syndrome are polymorphic in this natural population. PMID- 1311697 TI - Effects of P element insertions on quantitative traits in Drosophila melanogaster. AB - P element mutagenesis was used to construct 94 third chromosome lines of Drosophila melanogaster which contained on average 3.1 stable P element inserts, in an inbred host strain background previously free of P elements. The homozygous and heterozygous effects of the inserts on viability and abdominal and sternopleural bristle number were ascertained by comparing the chromosome lines with inserts to insert-free control lines of the inbred host strain. P elements reduced average homozygous viability by 12.2% per insert and average heterozygous viability by 5.5% per insert, and induced recessive lethal mutations at a rate of 3.8% per insert. Mutational variation for the bristle traits averaged over both sexes was 0.03Ve per homozygous P insert and 0.003Ve per heterozygous P insert, where Ve is the environmental variance. Mutational variation was greater for the sexes considered separately because inserts had large pleiotropic effects on sex dimorphism of bristle characters. The distributions of homozygous effects of inserts on the bristle traits were asymmetrical, with the largest effects in the direction of reducing bristle number; and highly leptokurtic, with most of the increase in variance contributed by a few lines with large effects. The inserts had partially recessive effects on the bristle traits. Insert lines with extreme bristle effects had on average greatly reduced viability. PMID- 1311699 TI - Molecular analysis of the maize wx-B3 allele indicates that precise excision of the transposable Ac element is rare. AB - The somatic and germinal behavior of the maize wx-B3 mutation indicates that this Ac allele rarely reverts. Endosperms containing wx-B3 display tiny and infrequent Wx revertant sectors while no significant reversion is detected when wx-B3 pollen is stained with I/KI. Previous studies of other transposable element alleles that revert infrequently have implicated low levels of element excision. Unlike these other alleles, the wx-B3 Ac element is indistinguishable from fully active Ac elements with respect to its structure, and its ability to transpose from the Wx gene or to trans-activate a Ds element. Characterization of somatic and germinal excision events lead us to conclude that excision of the wx-B3 Ac element almost always produces null alleles. Furthermore, the excellent correlation between the position of the wx-B3 mutation on the physical and genetic maps indicates that the Ac insertion is the only lesion of wx-B3. As a result, precise excision of this Ac should restore Wx function. The fact that revertant sectors and pollen grains are rare indicates that precise excision of Ac is also rare. The finding that the wx-B3 reversion frequency is comparable whether wx-B3 is hemizygous or over a wx allele with a wild-type insertion site illustrates a fundamental difference between the excision mechanisms of Ac and Drosophila P elements. PMID- 1311700 TI - Isolation of a clone which induces expression of the gene encoding the human tumor necrosis factor receptor. AB - Tumor necrosis factor (TNF) is a cytokine with pleiotropic effects upon cell growth, inflammation and immunologic responsiveness. High-affinity TNF receptors (TNFRs) of 55 and 75 kDa are found in many cell types. Using an Epstein-Barr virus (EBV)-based mammalian expression library, we have isolated a clone from human lymphoblastoid transfectants that induces overexpression of the TNFR encoding gene (TNFR). Transfectants overproducing the TNFR were isolated by multiple rounds of sorting on a fluorescence-activated cell sorter using fluorescent TNF ligand binding as the selection procedure. Among the sorted transfectants were cells producing approx. 150,000 receptors per cell (Kd of approx. 1 nM). These cells have multiple copies of the TNFR gene present as extrachromosomal plasmids. These cells also overproduced the mRNA for TNFR. Low Mr EBV episomes were isolated from these overproducing cells and used to transform Escherichia coli. One of the colonies isolated contained a plasmid encoding a portion of the noncoding region of the TNFR gene. Transfection of human lymphoblastoid cells with this DNA gave rise to high-level production of TNFR. Fluorescent TNF bound to these transfectants is fully and specifically displaced by an excess of TNF. The rescued clone contains approx. 10 kb of human genomic DNA including the 3'-untranslated region of TNFR and several Alu sequences; apparently during the selection procedure in human cells, recombination occurred to rescue a portion of the TNFR gene. Transient transfection was used to narrow down the region responsible for TNFR induction to 5.2 kb. The mechanism by which this clone induces TNFR expression has not been determined. PMID- 1311701 TI - Production in Escherichia coli of porcine type-I collagenase as a fusion protein with beta-galactosidase. AB - Porcine type-I collagenase (Colg-1) was produced as a fusion protein in Escherichia coli using the pAX5 expression vector. The fusion protein consists of beta-galactosidase at the N terminus joined to a collagen hinge region and a blood-coagulation factor Xa cleavage site linked to Colg-1. Recombinant collagenase (reColg-1) was biologically active in the form of a fusion protein and could be released by treatment with factor Xa to yield Colg-1 with the authentic N terminus (phenylalanine) found in vivo. The results show that reColg 1 produced in E. coli is folded correctly, cleaves type-I collagen into 1/4 and 3/4 fragments at the characteristic Colg-sensitive site, and is produced at high enough levels to generate a source of recombinant enzyme for x-ray crystallography studies. PMID- 1311702 TI - HLA-DQ beta chain can present mouse endogenous provirus MTV-9 product and clonally delete Tcr V beta 5+ and V beta 11+ T cells in transgenic mice. AB - The elusive Mls gene(s) are mouse mammary tumor virus genes. The endogenous cotolerogen involved in the clonal deletion of Tcr V beta 5.1, 5.2, and 11 in H 2E+ mouse strains has been narrowed down to MTV-9. We demonstrate that similar to H-2E alpha molecules, human DQw6 beta chain mediated clonal deletion of Tcr V beta 5.1, 5.2, and 11 also requires the MTV-9 gene product. This shows that human class II molecules can present mouse retroviral antigen. Further, backcross analysis involving [B10.M(DQb) x DBA/1] suggest a second cotolerogen in the B10.M background in the clonal deletion of V beta 5-bearing T cells. PMID- 1311703 TI - Quantitative immunohistochemical and biochemical correlates of connexin43 localization in rat brain. AB - We have shown by immunohistochemical methods that the gap junction protein connexin43 is heterogeneously distributed in rat brain (Yamamoto et al: J Comp Neurol 302:853, 1990). Here we have compared quantitatively the relative amount of connexin43 detected on Western blots of seven central nervous system (CNS) regions with the density of connexin43-immunoperoxidase reactivity in these regions. As has been observed on Western blots of several cell types, homogenates of these CNS regions contained two forms of connexin43, its dephospho form with an apparent mobility of approximately 41 kDa and its approximately 43 kDa phosphorylated form. While the relative quantities of connexin43 varied considerably among the brain regions, the ratio of the 43/41 kDa forms, 0.71, was relatively uniform (correlation coefficient, r = 0.92). Sections of brain processed for connexin43-immunolocalization by the peroxidase-antiperoxidase (PAP) method showed that chromogen deposition was linear with incubation time in reaction medium. Optical density of tissue connexin43-immunoreactivity in each of the seven areas plotted against the density of connexin43 bands on Western blots gave a correlation coefficient of r = 0.90. Connexin43-immunoreactivity had a similar appearance in sections processed by PAP or immunofluorescence procedures and consisted of isolated or aggregates of puncta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311704 TI - Production and disposition of 1-methyl-4-phenylpyridinium in primary cultures of mouse astrocytes. AB - Dopaminergic neurons are a primary target for 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) neurotoxicity. However, the conversion of MPTP to its neurotoxic 1-methyl-4-phenylpyridinium metabolite (MPP+) is likely to occur in astrocytes via the monoamine oxidase (MAO)-dependent formation of the 1-methyl-4 phenyl-2,3-dihydropyridinium intermediate (MPDP+). The main purpose of this study was to characterize the molecular mechanism(s) by which MPP+, once generated by astrocytes, may reach the extracellular space to become available for the active accumulation into dopaminergic neurons. Primary cultures of mouse astrocytes were used as an in vitro model system. After the addition of MPTP, levels of MPP+ were found to increase at constant rates both intracellularly and extracellularly at time points when no sign of cytotoxicity was evident. In contrast, MPDP+ levels remained quite stable during 4 days of incubation in the presence of MPTP. Finally, when astrocytes were allowed to accumulate MPP+ by pretreatment with either MPTP or MPP+ and then were incubated in fresh medium not containing MPTP or MPP+, intracellular levels of MPP+ rapidly declined and corresponding amounts of this compound were found in the incubation medium. Results of this study are compatible with the following conclusions: 1) the MPP+ accumulated in the extracellular compartment during incubations with MPTP is not released from astrocytes as a consequence of its own cytotoxic effects; 2) MPP+ can be formed extracellularly presumably via autoxidation of MPDP+ after this latter compound has been generated within astrocytes and has crossed astrocyte membranes; and 3) despite its charged chemical structure, MPP+ can cross the plasma membrane toward the extracellular space after being formed within astrocytes. PMID- 1311705 TI - Macrophage activation during Plasmodium chabaudi AS infection in resistant C57BL/6 and susceptible A/J mice. AB - Macrophage activation was examined in resistant C57BL/6 and susceptible A/J mice during the course of blood-stage infection with Plasmodium chabaudi AS. Three parameters of macrophage activation (lipopolysaccharide [LPS]- and malaria antigen-induced tumor necrosis factor [TNF] production in vitro, phorbol myristate acetate [PMA]-induced production of oxygen metabolites in vitro, and Ia antigen expression) were assessed during infection in populations of peritoneal and splenic macrophages recovered from infected mice of the two strains. The peak level of LPS-induced TNF production in vitro by splenic macrophages from both infected C57BL/6 and infected A/J mice occurred on day 7, which was 3 days before the peak of parasitemia. Although the kinetics of TNF production in vitro in response to either LPS, soluble malaria antigen, or intact parasitized erythrocytes varied in some of the other macrophage populations during infection, there was no significant difference in the peak level of production. Peritoneal and splenic macrophages from infected C57BL/6 mice exhibited significantly increased PMA-induced production of H2O2 in vitro on day 7. Peritoneal macrophages from infected A/J mice also exhibited significant PMA-induced H2O2 production on day 7, while production by splenic macrophages from these hosts was not increased in comparison with production by cells from normal animals. Only peritoneal macrophages from infected C57BL/6 mice produced significantly increased levels of O2-, and this occurred on day 7 postinfection. Ia antigen expression by both peritoneal and splenic macrophages from resistant C57BL/6 and susceptible A/J mice was significantly increased during P. chabaudi AS infection. However, the percentage of Ia+ peritoneal macrophages on days 8 and 10 postinfection and Ia+ splenic macrophages on day 3 postinfection was significantly higher in C57BL/6 than in A/J mice. Thus, these results demonstrate that macrophages from P. chabaudi AS-infected A/J mice exhibit defects in oxygen metabolism and Ia antigen expression which may contribute to the susceptibility of these hosts to this intraerythrocytic parasite. The cause-and-effect relationship between these defects and the susceptibility of A/J mice to P. chabaudi AS is unknown. PMID- 1311706 TI - Non-O1 Vibrio cholerae NRT36S produces a polysaccharide capsule that determines colony morphology, serum resistance, and virulence in mice. AB - Non-O1 Vibrio cholerae produced two distinct colony types, designated as opaque and translucent. NRT36S, a clinical isolate shown to be virulent in volunteers, produced predominantly opaque colonies, but translucent colonies appeared on subculture. Opaque variants were recovered exclusively following exposure to normal human serum or animal passage. A nonreverting translucent mutant of NRT36S, JVB52, was isolated following mutagenesis with the transposon Tn5 IS50L::phoA (TnphoA). Only translucent colonies were produced by a nonpathogenic environmental isolate, A5. Electron microscopic examination of the opaque form of NRT36S revealed thick, electron-dense, fibrous capsules surrounding polycationic ferritin-stained cells. The ferritin-stained material around translucent NRT36S or A5 was patchy or absent. JVB52 had a thin but contiguous capsular layer. The amount of ferritin-stained capsular material correlated with the amount of surface polysaccharide determined by phenol-sulfuric acid assay: opaque NRT36S had approximately three times as much polysaccharide as translucent NRT36S or A5 and four times as much as JVB52. The encapsulated, opaque variant of NRT36S was protected from serum bactericidal activity, while translucent non-O1 V. cholerae was readily killed. The encapsulated form also had increased virulence in mice. Our data provide the first indication that non-O1 V. cholerae strains can have a polysaccharide capsule. This capsule may be important in protecting the organism from host defenses and may contribute to the ability of some non-O1 V. cholerae strains to cause septicemia in susceptible hosts. PMID- 1311707 TI - Lipopolysaccharide O side chain of Yersinia enterocolitica O:3 is an essential virulence factor in an orally infected murine model. AB - The rfb gene cluster of Yersinia enterocolitica O:3, responsible for the biosynthesis of the O side chain, was previously cloned, and a Y. enterocolitica O:3 side chain-specific bacteriophage (phi YeO3-12) was isolated (A. Al-Hendy, P. Toivanen, and M. Skurnik, Microb. Pathog. 10:47-59, 1991). This paper describes the isolation and characterization of the bacteriophage phi YeO3-12-resistant mutant of Y. enterocolitica O:3, YeO3-R2. Lipopolysaccharide isolated from YeO3 R2 lacked the O side chain, as evidenced by silver staining and by immunoblots probed with a Y. enterocolitica O:3 O side chain-specific monoclonal antibody. The core was complete, as shown in immunoblots probed with an outer core-specific monoclonal antibody. In Southern blotting with the cloned Y. enterocolitica O:3 rfb region as a probe, there was no detectable difference in the hybridization pattern of chromosomal DNA isolated from YeO3-R2 and that isolated from wild-type Y. enterocolitica O:3. This suggests that a point mutation, rather than a large deletion, was responsible for the rough phenotype of YeO3-R2. The virulence of YeO3-R2 was determined in an orally infected desferal-attenuated murine model. The mutant was approximately 50-fold less virulent than the isogenic wild type. The ability of YeO3-R2 to reexpress O side chain, and hence full virulence, was reconstituted by complementing the chromosomal mutation in trans with the distal 6.5 kb of the Y. enterocolitica O:3 rfb region. This same 6.5-kb fragment transcomplemented a transposon mutation in the same area of the Y. enterocolitica O:3 rfb region when expressed in Escherichia coli. This transcomplementation implies that the rfb region of Y. enterocolitica O:3 is organized into at least two separate operons. PMID- 1311709 TI - A clarification of alpidem as an antidepressant. PMID- 1311708 TI - Reduced virulence of a Listeria monocytogenes phospholipase-deficient mutant obtained by transposon insertion into the zinc metalloprotease gene. AB - A phospholipase-deficient mutant, termed JL762, was obtained from a virulent strain of Listeria monocytogenes by screening a bank of 5,000 Tn1545 transposon induced mutants on 2.5% egg yolk brain heart infusion agar. As previously shown (J. Mengaud, C. Geoffroy, and P. Cossart, Infect. Immun. 59:1043-1049, 1991), the transposon insertion took place inside the gene mpl, which encodes a zinc metalloprotease. By Western blot (immunoblot) analysis, we showed that loss of phospholipase activity was associated with loss of a 29-kDa zinc-dependent phosphatidylcholine-phospholipase C (PC-PLC) in culture supernatant of JL762 and of EGD-SmR incubated with ion chelator. As the parental strain, JL762 still produced in supernatants approximately 33-kDa proteins antigenically closely related to the 29-kDa PC-PLC. These results strongly suggest that the zinc metalloprotease of L. monocytogenes might play a role in the maturation of the 29 kDa PC-PLC. Although the uptake and the intracellular growth of bacteria were not affected in vitro, we found that the virulence of mutant JL762 was strongly impaired in the mouse. PMID- 1311710 TI - The total-contact cast for management of neuropathic plantar ulceration of the foot. AB - Seventy-one neuropathic ulcers of the foot in sixty-six patients were treated with the use of a total-contact cast. The ulcers had been present for an average of five months (range, one to twenty-nine months) and were graded according to the Wagner classification; only patients who had grade-I or grade-II lesions were treated with a total-contact cast. The diameter of the ulcer averaged 3.5 centimeters (range, 1.5 to 15.5 centimeters). Sixty-four (90 per cent) of seventy one ulcers were healed at a mean of five and one-half weeks (range, one to fourteen weeks). A deep infection developed in two patients during treatment. Twenty-two ulcers (31 per cent) recurred within eighteen months after initial healing; nineteen (86 per cent) of them healed after an average of two weeks in a second cast. Recurrent ulceration was usually associated with an underlying fixed deformity or osseous prominence. The total-contact cast provided safe, reliable, and cost-effective treatment for patients who had neuropathic ulcers of the foot. PMID- 1311712 TI - Protein phosphatase type 1 in mammalian cell mitosis: chromosomal localization and involvement in mitotic exit. AB - We have examined the role of protein phosphatase type 1 (PP-1) in mammalian cell mitosis. Immunofluorescence using anti-PP-1 antibodies revealed that PP-1, which is mainly localized in the cytoplasm of G1 and S phase cells, accumulates in the nucleus during G2 phase and intensely colocalizes with individual chromosomes at mitosis. This increase in nuclear PP-1 in G2/M cells was confirmed by immunoblotting on subcellular fractions. Microinjection of neutralizing anti-PP-1 antibodies before division blocked cells at metaphase, whereas injection of PP-1 in one pole of an anaphase B cell accelerated cytokinesis and the reflattening of the injected cell. These results reveal a specific cell cycle-dependent redistribution of PP-1 and its involvement in reversing p34cdc2-induced effects after mid-mitosis in mammalian cells. PMID- 1311711 TI - Evidence for the regulation of exocytic transport by protein phosphorylation. AB - We investigated the effects of the protein phosphatase inhibitors okadaic acid and microcystin-LR upon transport of newly synthesized proteins through the exocytic pathway. Treatment of CHO cells with 1 microM okadaic acid rapidly inhibited movement of a marker protein (vesicular stomatitis virus G protein) from the endoplasmic reticulum to the Golgi compartment. Both okadaic acid and microcystin-LR also inhibited transport in an in vitro assay reconstituting movement to the Golgi compartment, at concentrations equivalent to those required to inhibit phosphorylase phosphatase activity. Inhibition both in vivo and in vitro could be antagonized by protein kinase inhibitors, suggesting that protein phosphorylation was directly responsible for this effect. An early stage in the transport reaction associated with vesicle formation or targeting was inhibited by protein phosphorylation, which could be reversed by fractions enriched in protein phosphatase 2A. Protein kinase antagonists did not inhibit transport between sequential compartments of the exocytic pathway in vitro, suggesting that protein phosphorylation is not itself required for vesicular transport. During mitosis, vesicular transport is inhibited simultaneous to the activation of maturation-promoting factor. It is proposed that the inhibition caused by okadaic acid and microcystin-LR involves a similar mechanism to that responsible for the mitotic arrest of vesicular transport. PMID- 1311713 TI - The activity of cAMP-dependent protein kinase is required at a posttranslational level for induction of voltage-dependent sodium channels by peptide growth factors in PC12 cells. AB - The synthesis and expression of voltage-dependent sodium (Na) channels is a crucial aspect of neuronal differentiation because of the central role these ion channels play in the generation of action potentials and the transfer of information in the nervous system. We have used rat pheochromocytoma (PC12) cell lines deficient in cAMP-dependent protein kinase (PKA) activity to examine the role of PKA in the induction of Na channel expression by nerve growth factor (NGF) and basic FGF (bFGF). In the parental PC12 cell line both NGF and bFGF elicit an increase in the density of functional Na channels, as determined from whole-cell patch clamp recordings. This increase does not occur in two PC12 cell lines deficient in both isozymes of PKA (PKAI and PKAII), and is strongly reduced in a third line deficient in PKAII, but not PKAI. Despite the inability of the neurotrophic factors to induce functional Na channel expression in the PKA deficient cells, Northern blot hybridization studies and saxitoxin binding assays of intact cells indicate that NGF and bFGF are still capable of eliciting increases in both Na channel mRNA and Na channel protein in the membrane. Thus, PKA activity appears to be necessary at a posttranslational step in the synthesis and expression of functional Na channels, and thereby plays an important role in determining neuronal excitability. PMID- 1311714 TI - Human fat cells possess a plasma membrane-bound H2O2-generating system that is activated by insulin via a mechanism bypassing the receptor kinase. AB - Insulin caused a transient increase in H2O2 accumulation in human fat cell suspensions that was observed only in the presence of an inhibitor of catalase and heme-containing peroxidases, such as azide, and reached peak levels of 30 microM within 5 min. The cells contained a plasma membrane-bound NADPH oxidase, producing 1 mol H2O2/mol of NADPH oxidation, that was activated on exposure of intact cells to insulin at contrations that are physiologically relevant (0.1-10 nM). The hormone effect was rapid and was due to a selective increase in substrate affinity. The enzyme was magnesium dependent, required a flavine nucleotide for optimal activity, and was most active at pH 5.0-6.5. In contrast to all other hormone- or cytokine-sensitive NADPH oxidases that have been characterized in sufficient detail, the human fat cell oxidase retained its hormone responsiveness after cell disruption, and only Mn2+, but no ATP, was required for a ligand-induced activation in crude plasma membranes. The results demonstrate that insulin utilizes tyrosine kinase-independent pathways for receptor signaling and strongly support the view that H2O2 contributes to the intracellular propagation of the insulin signal. PMID- 1311716 TI - Endothelium-derived relaxing factor inhibits transport and increases cGMP content in cultured mouse cortical collecting duct cells. AB - Stimulation of the release of endothelium-derived relaxing factor (EDRF) in the kidney has been shown to result in natriuresis without affecting glomerular filtration rate. This may be due to EDRF directly regulating solute transport in the cortical collecting duct (CCD). To test this hypothesis, we measured the effect of bradykinin (Bk) or acetylcholine (Ach) on short-circuit current (Isc; a measure of active transport) in a CCD cell line (M-1), in the presence or absence of cow pulmonary artery endothelial (CPAE) cells. 10(-9) M Bk or 10(-7) M Ach had no effect on M-1 Isc in which CPAE cells were absent. The addition of CPAE cells to M-1 cells also did not affect M-1 Isc. On the other hand, when 10(-9) M Bk or 10(-7) M Ach were added to M-1 cells in the presence of CPAE cells, Isc decreased from 43 +/- 4.5 to 26 +/- 4 and 64 +/- 9 to 33 +/- 4 microA/cm2, respectively (P less than 0.001). Nitroarginine (N-Arg, 10(-4) M), a competitive inhibitor of EDRF production, blocked the inhibition in M-1 Isc due to both agonists. Since cGMP is the second messenger of EDRF in vascular smooth muscle, we measured the effects of Bk on cGMP production in M-1 cells in the presence and absence of CPAE cells. Bk increased cGMP content in M-1 cells in the presence of CPAE cells from 33 +/- 3.4 to 132 +/- 11.7 fmol/10(6) M-1 cells (P less than 0.001). When cultures of M-1 and CPAE cells were treated with N-Arg and challenged with Bk, Bk's effect on cGMP was partially blocked (61.4 +/- 12 fmol/10(-6) M-1 cells; NS). These data suggest that EDRF inhibits transport and increases cGMP content in M-1 cells. PMID- 1311715 TI - A human lymphoma cell line with multiple immunoglobulin rearrangements. AB - The development of a cell culture system efficient in the establishment of lymphoma cell lines has made it possible to dissect basic biological and molecular aspects of lymphoma cells. We have established a lymphoma cell line from a patient with B cell lymphoma. The cell line has a complex karyotype with translocations involving bands 8q24, 14q32, and 18q21. Molecular analysis revealed that the Myc gene was rearranged; we were unable to demonstrate rearrangement of the Bcl-2 gene. Evaluation of the structure of the heavy chain Ig genes revealed that the cell line carried the same rearrangements as the cells from which the cell line was derived. The pattern of rearrangement, however, was unusual in that there were at least four rearranged bands when DNA cut with HindIII was probed with a fragment of the heavy chain joining region. To further characterize the cell line, subclones were derived. Individual subclones had the same pattern of rearrangement as the parent cell line. The results of these studies provide evidence that multiple rearranged Ig genes may be present in a single clone of cells. PMID- 1311717 TI - Beta-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms. AB - In order to investigate the general cause of beta-adrenergic receptor neuroeffector abnormalities in the failing human heart, we measured ventricular myocardial adrenergic receptors, adrenergic neurotransmitters, and beta adrenergic receptor-effector responses in nonfailing and failing hearts taken from nonfailing organ donors, subjects with endstage biventricular failure due to idiopathic dilated cardiomyopathy (IDC), and subjects with primary pulmonary hypertension (PPH) who exhibited isolated right ventricular failure. Relative to nonfailing PPH left ventricles, failing PPH right ventricles exhibited (a) markedly decreased beta 1-adrenergic receptor density, (b) marked depletion of tissue norepinephrine and neuropeptide Y, (c) decreased adenylate cyclase stimulation in response to the beta agonists isoproterenol and zinterol, and (d) decreased adenylate cyclase stimulation in response to Gpp(NH)p and forskolin. These abnormalities were directionally similar to, but generally more pronounced than, corresponding findings in failing IDC right ventricles, whereas values for these parameters in nonfailing left ventricles of PPH subjects were similar to values in the nonfailing left ventricles of organ donors. Additionally, relative to paired nonfailing PPH left ventricles and nonfailing right ventricles from organ donors, failing right ventricles from PPH subjects exhibited decreased adenylate cyclase stimulation by MnCl2. These data indicate that: (a) Adrenergic neuroeffector abnormalities present in the failing human heart are due to local mechanisms; systemic processes do not produce beta-adrenergic neuroeffector abnormalities. (b) Pressure-overloaded failing right ventricles of PPH subjects exhibit decreased activity of the catalytic subunit of adenylate cyclase, an abnormality not previously described in the failing human heart. PMID- 1311718 TI - Adenosine regulates a chloride channel via protein kinase C and a G protein in a rabbit cortical collecting duct cell line. AB - We examined the regulation by adenosine of a 305-pS chloride (Cl-) channel in the apical membrane of a continuous cell line derived from rabbit cortical collecting duct (RCCT-28A) using the patch clamp technique. Stimulation of A1 adenosine receptors by N6-cyclohexyladenosine (CHA) activated the channel in cell-attached patches. Phorbol 12,13-didecanoate and 1-oleoyl 2-acetylglycerol, activators of protein kinase C (PKC), mimicked the effect of CHA, whereas the PKC inhibitor H7 blocked the action of CHA. Stimulation of A1 adenosine receptors also increased the production of diacylglycerol, an activator of PKC. Exogenous PKC added to the cytoplasmic face of inside-out patches also stimulated the Cl- channel. Alkaline phosphatase reversed PKC activation. These results show that stimulation of A1 adenosine receptors activates a 305-pS Cl-channel in the apical membrane by a phosphorylation-dependent pathway involving PKC. In previous studies, we showed that the protein G alpha i-3 activated the 305-pS Cl- channel (Schwiebert et al. 1990. J. Biol. Chem. 265:7725-7728). We, therefore, tested the hypothesis that PKC activates the channel by a G protein-dependent pathway. In inside-out patches, pertussis toxin blocked PKC activation of the channel. In contrast, H7 did not prevent G protein activation of the channel. We conclude that adenosine activates a 305-pS Cl- channel in the apical membrane of RCCT-28A cells by a membrane-delimited pathway involving an A1 adenosine receptor, phospholipase C, diacylglycerol, PKC, and a G protein. Because we have shown, in previous studies, that this Cl- channel participates in the regulatory volume decrease subsequent to cell swelling, adenosine release during ischemic cell swelling may activate the Cl-channel and restore cell volume. PMID- 1311719 TI - Platelet-derived growth factor receptors on macrovascular endothelial cells mediate relaxation via nitric oxide in rat aorta. AB - The effects of platelet-derived growth factor (PDGF) were studied in isolated rings of rat aorta contracted submaximally to phenylephrine. The BB isoform of PDGF elicited relaxation in rings with endothelium and further contraction in rings without endothelium. Both the endothelium-dependent relaxation and endothelium-independent contraction occurred at concentrations known to induce PDGF receptor-mediated responses in cultured cells. Furthermore, the relaxation was isoform specific. This conclusion is supported by the unique ability of PDGF BB to induce endothelium-dependent relaxations, as well as by studies showing isoform specific, concentration-dependent desensitization of PDGF-BB relaxation. The relaxation induced by PDGF-BB was prevented by N omega-nitro-L-arginine. It was also observed that endothelium-independent contractions to the AB and AA isoforms of PDGF were less than those to PDGF-BB. Contrary to the widely held view that PDGF receptors are not present on the endothelium of macrovessels, these studies provide evidence for an endothelium-dependent, nitric oxide mediated relaxation of rat aorta caused by PDGF via PDGF beta beta-receptors. PMID- 1311720 TI - High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells. AB - We studied the nature of insulin receptor binding in MCF-7 breast cancer cells. In both intact cells and solubilized receptor preparations, high-affinity insulin binding was seen. However, unlabeled insulin-like growth factor-I (IGF-I) was five-fold more potent in inhibiting 125I-insulin binding than insulin itself. With monoclonal antibodies to the insulin receptor, 30% of 125I-insulin binding was inhibited. In contrast when alpha-IR3, a monoclonal antibody that recognizes typical IGF-I receptor, was employed over 60% of 125I-insulin binding was inhibited. The B29-MAB-125I-insulin photoprobe was then cross-linked to MCF-7 membranes. Cross-linking was inhibited by both unlabeled insulin and IGF-I. Further, the B29-MAB-125I-insulin photoprobe cross-linked to MCF-7 membranes was strongly immunoprecipitated by alpha-IR3. Employing sequential affinity chromatography with insulin-Affi-gel followed by insulin receptor monoclonal antibody agarose, atypical insulin binding activity was separated from insulin receptor binding activity. This atypical receptor had intrinsic tyrosine kinase activity. Both insulin and IGF-I stimulated the phosphorylation of the receptor's beta subunit. In MCF-7 cells both IGF-I and insulin stimulated [3H]thymidine incorporation; alpha-IR3 blocked all of the IGF-I effect but only 50-60% of the insulin effect. This study demonstrates in MCF-7 cells that, in addition to typical insulin and IGF-I receptors, there is another receptor that binds both insulin and IGF-I with high affinity. PMID- 1311721 TI - Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase. AB - High level expression of the nm23-H1 gene, which encodes for a nucleoside diphosphate kinase, has been found to correlate with diminished metastasis in some tumors but not in others. We have previously identified the protein product of the nm23-H1 gene in two-dimensional electrophoretic gels and have designated it p19/nm23. In neuroblastoma, higher levels of p19/nm23, which are associated with amplification of the N-myc oncogene, large tumor mass, and metastasis, were observed in advanced stage tumors compared with limited stage disease. Because of the variable expression of nm23-H1 in different tumors, we have investigated the relationship between amounts of the protein and cell proliferation. The levels of p19/nm23 were compared between resting and mitotically stimulated normal human PBLs and in leukemia cells. The amount of p19/nm23 increased in normal lymphocytes in response to mitotic stimulation and paralleled the increase in DNA synthesis. In leukemia cells obtained from patients with different subtypes of acute leukemia, p19/nm23 levels were also increased relative to resting normal lymphocytes. Treatment of mitotically stimulated lymphocytes with cyclosporin, which inhibits proliferation, blocked the increase in p19/nm23; treatment of the leukemia cell line HL-60 with dimethylsulfoxide, which induces terminal differentiation, resulted in diminished levels of p19/nm23. Our data therefore provide evidence that nm23-H1 expression is related to cell proliferative activity. PMID- 1311722 TI - Effect of angiotensin II on ammonia production and secretion by mouse proximal tubules perfused in vitro. AB - The effects of angiotensin II on total ammonia (tNH3) production and net secretion were investigated using in vitro microperfused mouse S2 proximal tubule segments incubated in Krebs-Ringer bicarbonate buffer containing 0.5 mM L glutamine. Basolateral exposure of mouse S2 segments to 10(-11), 10(-10), and 10( 9) M angiotensin II stimulated tNH3 production rates by 23, 52, and 49%, respectively. Addition of 10(-6) M angiotensin II inhibited the tNH3 production rate by 34%. 10(-10) M angiotensin II inhibited net luminal secretion of tNH3 in the presence of enhanced luminal acidification and in the absence of altered luminal tNH3 efflux rates. Measurements of intracellular pH (pHi) and intracellular calcium concentration [( Ca2+]i) suggested that the effects of angiotensin II on tNH3 production were not mediated by changes in pHi but by the stimulatory effect of angiotensin II correlated with increased [Ca2+]i. Inhibition of the calcium-calmodulin-dependent pathway with W-7 blocked the stimulatory effect of 10(-10) M angiotensin II on tNH3 production and luminal acidification. These results indicate that angiotensin II has concentration dependent effects on tNH3 production; that its action to stimulate tNH3 production may be mediated by rises in [Ca2+]i and the calcium-calmodulin pathway; and that angiotensin II, at concentrations that stimulate tNH3 production, inhibits net luminal ammonia secretion by a mechanism that is not mediated by diminished luminal acidification or by changes in luminal ammonia efflux rates. PMID- 1311723 TI - Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure. AB - 24 d of rapid ventricular pacing induced dilated cardiomyopathy with both systolic and diastolic dysfunction in conscious, chronically instrumented dogs. We studied mechanical properties and intracellular calcium (Ca2+i) transients of trabeculae carneae isolated from 15 control dogs (n = 32) and 11 dogs with pacing induced cardiac failure (n = 26). Muscles were stretched to maximum length at 30 degrees C and stimulated at 0.33 Hz; a subset (n = 17 control, n = 17 myopathic) was loaded with the [Ca2+]i indicator aequorin. Peak tension was depressed in the myopathic muscles, even in the presence of maximally effective (i.e., 16 mM) [Ca2+] in the perfusate. However, peak [Ca2+]i was similar (0.80 +/- 0.13 vs. 0.71 +/- 0.05 microM; [Ca2+]o = 2.5 mM), suggesting that a decrease in Cai2+ availability was not responsible for the decreased contractility. The time for decline from the peak of the Cai2+ transient was prolonged in the myopathic group, which correlated with prolongation of isometric contraction and relaxation. However, similar end-diastolic [Ca2+]i was achieved in both groups (0.29 +/- 0.05 vs. 0.31 +/- 0.02 microM), indicating that Cai2+ homeostasis can be maintained in myopathic hearts. The inotropic response of the myopathic muscles to milrinone was depressed compared with the controls. However, when cAMP production was stimulated by pretreatment with forskolin, the response of the myopathic muscles to milrinone was improved. Our findings provide direct evidence that abnormal [Ca2+]i handling is an important cause of contractile dysfunction in dogs with pacing-induced heart failure and suggest that deficient production of cAMP may be an important cause of these changes in excitation-contraction coupling. PMID- 1311724 TI - Effects of inorganic iron and myoglobin on in vitro proximal tubular lipid peroxidation and cytotoxicity. AB - Recent in vivo studies suggest that heme Fe causes proximal tubular lipid peroxidation and cytotoxicity, thereby contributing to the pathogenesis of myoglobinuric (Mgb) acute renal failure. Because hydroxyl radical (.OH) scavengers [dimethylthiourea (DMTU), benzoate, mannitol] can mitigate this injury, it is postulated that .OH is a mediator of Mgb-induced renal damage. The present study has tested these hypotheses using an isolated rat proximal tubular segment (PTS) system. An equal mixture of Fe2+/Fe3+ (4 mM total), when added to PTS, caused marked cytotoxicity [as defined by lactate dehydrogenase (LDH) release] and lipid peroxidation [assessed by malondialdehyde (MDA) increments]. Fe2+ or Fe3+ alone each induced massive MDA elevations, but only Fe2+ caused cytotoxicity. Although both DMTU and benzoate decreased LDH release during the Fe2+/Fe3+ challenge, mannitol and GSH did not, despite equivalent reductions in .OH (gauged by the salicylate trap method). GSH and catalase (but not DMTU, benzoate, or mannitol) decreased MDA concentrations, suggesting the Fe-driven lipid peroxidation was more H2O2 than .OH dependent. Deferoxamine totally blocked Fe-induced LDH release, even under conditions in which it caused an apparent increase in .OH generation. Mgb paradoxically protected against Fe-mediated PTS injury, an effect largely reproduced by albumin. In conclusion, these data suggest that: (a) Fe can cause PTS lipid peroxidation and cytotoxicity by a non .OH-dependent mechanism; (b) Fe-mediated cytotoxicity and lipid peroxidation are not necessarily linked; and (c) Mgb paradoxically protects PTS against Fe mediated injury, suggesting that: (i) Mgb Fe may require liberation from its porphyrin ring before exerting toxicity; and (ii) the protein residue may blunt the resulting injury. PMID- 1311725 TI - Clinical evaluation of enzyme immunoassay in rapid diagnosis of herpes simplex infections. AB - AIMS: To evaluate the performance of antigen detection by IDEIA (NovoNordisk Ltd) in the rapid diagnosis of potentially serious herpes simplex (HSV) infections. METHODS: Nine hundred and twelve specimens from a variety of clinical sites, including ocular, mucocutaneous, respiratory and genital material, urines and necropsy tissue, were compared by enzyme immunoassay (EIA) and conventional culture for the presence of HSV. RESULTS: The EIA performed to a high level of sensitivity and specificity using a variety of specimen types. Some problems were encountered using cervical swabs from pregnant women and necropsy brain tissue. Analysis of clinical and contact history data of most patients giving discrepant results supported the evidence of recent HSV infection obtained by EIA. The mean culture time was 2.4 days (range one to eight days). CONCLUSIONS: The HSV EIA test performed to a high level of sensitivity (93.7%) and specificity (96.6%) when compared with culture using a variety of clinical material. These results assumed cell culture was 100% sensitive and specific. The actual performance of the EIA test is probably much higher. This approach to rapid HSV diagnosis should be used more widely, particularly in potentially serious cases. PMID- 1311726 TI - Effects of whole cottonseed or niacin or both on casein synthesis by lactating Holstein cows. AB - Forty Holstein cows in late lactation were offered diets containing niacin and whole cottonseed: 1) 0 g/d, 0%; 2) 0 g/d, 15%; 3) 6 g/d, 0%; and 4) 6 g/d, 15%, to evaluate effects on milk casein synthesis. Cows fed diet 1 had the highest DMI. The FCM (21.4 vs. 18.7 kg/d) and milk fat percentage (4.08 vs. 3.81) were higher for cows fed diet 1 than for those fed diet 4. Milk protein percentage (3.61 vs. 3.50) was higher for cows fed diet 1 than for those fed diet 2. Casein N, as a percentage of total N, was higher (71.9 vs. 68.0%) in milk from cows fed diet 1 than those fed diet 3. Insulin tended to be elevated in cows on the diets containing niacin, but glucose was not affected. Plasma niacin was elevated in cows on the diets supplemented with niacin compared with diet 1. Plasma AA were changed only slightly by treatments. The beneficial effect of niacin on milk casein synthesis, noted in our earlier work when cows were fed whole cottonseed, was not evident in this study with cows in late lactation and during hot weather. PMID- 1311727 TI - Dietary fiber and milk yield, mastication, digestion, and the rate of passage in goats fed alfalfa hay. AB - Two experiments were conducted to study the effect of intake of fiber on productive performance of high producing dairy goats during early to midlactation. Four dietary treatments were isonitrogenous and consisted of combinations of chopped alfalfa hay and concentrate, yielding 14, 18, 22, and 26% ADF. In Experiment 1, 40 multiparous Alpine does were used in a completely randomized block design. Milk fat content and total chewing time increased, and milk yield tended to decrease, as dietary ADF intake increased. Chewing efficiency [min/(g x kg BW.75)] for DM decreased, whereas that for ADF increased as ADF intake increased. Prediction equations were the following: milk fat yield, g/d = 115.78 - .128 x ADF intake, g/d + .00021 X (ADF intake)2 (r = .55); total chewing time, min/d = 345.33 + .32 x ADF intake, g/d (r = .60). In Experiment 2, 20 does were used in a completely randomized design. Apparent digestibilities of DM and energy decreased as dietary ADF intake increased. Rumen turnover rate and transit time of liquid were affected by ADF intake. Transit time of hay decreased as ADF intake increased. Intake of ADF affected pH and ammonia, acetate, and butyrate concentrations in the rumen. Acetate to propionate ration increased with ADF intake. No apparent trends were observed in whole blood beta-hydroxybutyrate or in plasma NEFA concentrations related to ADF intake. It appeared that DMI and milk fat yield leveled at 22% ADF or 43% NDF. For lactating dairy goats producing more than 3.5 kg/d of milk, calculated fat output reached a plateau when they consumed 587 g/d of ADF and spent 512 min/d chewing. PMID- 1311728 TI - Effect of copper and cobalt addition on digestion and growth in heifers fed diets containing alfalfa silage or corn crop residues. AB - Copper and cobalt were added to the diet of heifers in excess of NRC recommendations for these minerals. In Experiment 1, the rate of DM disappearance from dacron bags placed in the rumen was increased by the additional dietary Cu and Co for alfalfa hay (14.6 vs. 8.4%/h) and corn cobs (5.8 vs. 3.1%/h) but did not affect the DM disappearance rate for corn crop residue silage (3.6 vs. 3.4%/h). In Experiment 2, additional Cu and Co increased DM disappearance rate of corn crop residue silage (6.2 vs. 3.4%/h) but did not influence the rate of alfalfa hay (8.6 vs. 7.6%/h). In Experiment 3, a random design with a 2 x 2 factorial arrangement was used. The diet consisted of 45% corn crop residue silage, 35% alfalfa silage containing 60 or 40% DM, 18% high moisture corn, and 2% vitamin and mineral mix with or without added Cu and Co, respectively. Each of the four diets was group-fed to 9 light and 11 heavy Holstein heifers. Growth rate was lower with Cu and Co supplementation, but DM digestibility was improved by the additional Cu and Co. These results indicate that addition of Cu and Co above the NRC requirements may aid in digestion of low quality forages. PMID- 1311729 TI - Primary cutaneous adenoid cystic carcinoma treated with Mohs micrographic surgery toluidine blue technique. AB - A patient with primary cutaneous adenoid cystic carcinoma treated with Mohs surgery is presented. This tumor is characterized clinically by frequent local recurrences and infrequent metastases. Histologically it demonstrates cribiform islands of tumor cells with an abundance of mucin. Because toluidine blue stains this mucin metachromatically, it may be superior to hematoxylin and eosin for identifying the presence of this tumor. We recommend Mohs micrographic surgery with toluidine blue staining technique for the treatment of adenoid cystic carcinoma. PMID- 1311730 TI - Relation of serum zinc and copper to lipids and lipoproteins: the Yi People Study. AB - The relations of serum zinc (Zn) and copper (Cu) to serum total cholesterol (TC), low-density-lipoprotein and high-density-lipoprotein cholesterol (LDL-C and HDL C) and triglycerides were investigated in a population-based sample of 399 men in Southern China. Serum Cu was inversely related to HDL-C (r = -0.21), while Zn/Cu ratio showed a positive association (r = 0.19). These relationships remained significant after adjusting for age, body mass index (kg/m2), physical activity, tobacco smoking and dietary cholesterol, fat, and fiber. While no significant association was observed between serum Cu and serum TC in univariate analysis, a significant negative association was observed in multivariate analysis, after adjustment for the above mentioned independent variables. No significant association between serum Cu and LDL-C was found. These observations, as well as those reported in other studies reviewed herein, suggest that Cu is implicated in the metabolism of HDL-C, although the mechanism involved is not fully understood. No significant associations were found between serum Zn and the lipid variables. PMID- 1311731 TI - Binding of sperm to somatic cells via HLA-DR. Modulation by sulfated carbohydrates. AB - We have shown previously that human sperm bind and enter leukocytes expressing surface HLA class II molecules. In the present study, mutant B lymphoblastoid cells and HLA-DR-transfected murine 3T3 fibroblasts are used to confirm that HLA class II molecules are somatic cell receptors for sperm. Further, for isolated HLA-DR expressed on murine cells, we show that sperm receptor activity requires the presence of sulfated carbohydrates. As carriers of multiple HLA-DR binding ligands, sperm may 1) mimic the target cell-activating effects of anti-DR antibody and 2) bind HIV through CD4-like or alternate receptors. By these or other mechanisms, sperm/somatic cell interactions in the female reproductive tract may affect fertility and potentiate the sexual transmission of AIDS. PMID- 1311733 TI - Beta 2-adrenoceptor stimulation increases the number of antigen-specific precursor B lymphocytes that differentiate into IgM-secreting cells without affecting burst size. AB - Previous studies have shown that early addition of a beta 2-adrenergic agonist to whole splenocyte cultures immunized with SRBC induced an increase in the number of cells secreting Ag-specific antibody. Because of the low frequency of Ag specific B lymphocytes in these cultures, it has been difficult to determine the cellular mechanism by which this increase is produced. To gain insight into this cellular mechanism, the present study was designed to evaluate the responsiveness of TNP-specific B lymphocytes cultured at both high density and limiting dilution with keyhole limpet hemocyanin (KLH)-specific, IL-4-producing Th lymphocytes, TNP KLH, and the beta 2-adrenergic agonist, terbutaline. The results showed that a maximal twofold increase in both the number of anti-TNP IgM-secreting cells and the amount of anti-TNP IgM secretion occurred in terbutaline-exposed lymphocytes after 5 days of bulk culture. This response occurred in a concentration-dependent manner and was inhibited by concomitant culture with beta-adrenoceptor antagonists. No appreciable change was measured in the level of either IgG1 secretion in terbutaline plus Ag-exposed bulk cultures or MHC class II expression on terbutaline plus Ag-exposed TNP-specific B lymphocytes as compared with Ag alone. These data raised the possibility that beta 2-adrenoceptor stimulation induced either the differentiation of a larger proportion of TNP-specific B lymphocyte precursors into anti-TNP IgM-secreting cells, or the extensive proliferation of a constant number of TNP-specific B lymphocyte precursors, or both. Limiting dilution results showed that beta 2-adrenoceptor stimulation induced a twofold increase in the number of TNP-specific B lymphocyte precursors that differentiated into anti-TNP IgM-secreting cells, without affecting the number of anti-TNP IgM-secreting cells produced by each precursor clone. PMID- 1311732 TI - N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) protects thymocytes from programmed cell death. AB - Gamma-irradiation, glucocorticoid hormones, and calcium ionophores stimulate a suicide process in thymocytes, known as apoptosis or programmed cell death, that involves internucleosomal DNA fragmentation by a Ca(2+)- and Mg(2+)-dependent nuclear endonuclease. In this study we report that N-(2-mercaptoethyl)-1,3 propanediamine (WR-1065) blocked DNA fragmentation and cell death in thymocytes exposed to gamma-radiation, dexamethasone, or calcium ionophore A23187. WR-1065 protected the thymocytes from radiation-induced apoptosis when incubated with cells after irradiation but not before and/or during irradiation. WR-1065 inhibited Ca(2+)- and Mg(2+)-dependent DNA fragmentation in isolated thymocyte nuclei. Our results suggest that WR-1065 protects thymocytes from apoptosis by inhibiting Ca(2+)- and Mg(2+)-dependent nuclear endonuclease action. PMID- 1311734 TI - Determination of anti-neutrophil cytoplasm antibodies (ANCA) specificity by immunofluorescence on chronic myelocytic leukemia cells. AB - ANCA positive sera, detected by the standard immunofluorescence method, derived from 37 patients with vasculitis were studied using formalin-acetone fixed chronic myelocytic leukemia cells (CML). All 37 sera were positive on CML cell smears. Furthermore formalin-actone fixation selectively impaired antinuclear antibody binding without reducing ANCA staining and thus facilitated differentiation of these autoantibodies which is often difficult with the standard immunofluorescence method. Two unequivocal and mutually exclusive ANCA binding patterns were identified using the CML smears: (1) type I with diffuse granular binding confined to the polymorphonuclear (PMN) cell lineage and preferentially staining immature cells; (2) type II with similar binding to the PMN cell lineage and, in addition, granular staining of the basophils. All type I antibodies were associated with a c-ANCA pattern suggesting that the major antigen recognized by these antibodies, recently identified as proteinase 3, is not detectable in basophils. The type II pattern was detected in both p-ANCA (84%) and c-ANCA (16%) positive sera. The type I sera remained positive on PMN cells from a myeloperoxidase (MPO) deficient subject and anti-MPO antibodies could not be detected in this group by ELISA. Conversely the type II pattern occurred in the presence of anti-MPO antibodies identified by immunofluorescence, ELISA and dot-blot with the exception of a single serum with antilactoferrin antibody. Type I binding only was observed in Wegener's granulomatosis (WG) but both patterns were found in microscopic polyarteritis (MPA) and rapidly progressive glomerulonephritis (RPGN). PMID- 1311735 TI - Caveats for the use of surface-adsorbed protein antigen to test the specificity of antibodies. AB - Rabbit antisera against apo-cytochrome c, which was prepared by removal of the covalently bound heme prosthetic group from yeast iso-1 cytochrome c, were tested for reactivity against native yeast iso-1-cytochrome c. When the antigen was adsorbed to a microtiter plate in a conventional enzyme-linked immunosorbent assay (ELISA), the antisera were unable to distinguish between their cognate antigen apo-cytochrome c, a random coil protein, and native cytochrome c, a small globular protein of remarkable conformational stability in solution. However, when the assay was conducted under conditions where antigen and antibody were free to associate in solution, that is in a solution-phase radioimmunoassay (RIA), the antisera were highly specific for apo-cytochrome c. Similarly, antibodies induced by native cytochrome c and discriminating strongly between native and apo-cytochrome c in a solution-phase RIA, did not distinguish between native and apo-cytochrome c in a solid-phase ELISA. This discrepancy of results obtained by different immuno assay procedures clearly indicates that adsorption to plastic alters the antigenic structure of even a conformationally stable protein such as cytochrome c. A conventional solid-phase ELISA strongly selects for those antibodies that recognize the unfolded antigen. The results presented warrant serious thoughts about previous reports on anti-peptide antibodies reacting with native whole protein molecules, as tested by those ELISA procedures that have the protein antigen adsorbed to plastic. PMID- 1311736 TI - Methods for phenotyping polarized and locomotor human lymphocytes. AB - Lymphocytes show heterogeneity both in phenotype and in locomotor activity; methods which permit the simultaneous assessment of both are therefore useful. The activation of locomotion may be dependent on interactions between lymphocytes and accessory cells, making it necessary to study mixed cell populations. We describe here two in vitro procedures which do this. Firstly the lymphocyte polarization assay has been adapted by using the alkaline phosphatase-anti alkaline phosphatase method (APAAP) after fixation with glutaraldehyde. Secondly, we have allowed lymphocytes to invade collagen gels and then digested the gel with collagenase to recover the locomotor population. This can then be phenotyped by immunofluorescence using a fluorescence-activated cell sorter (FACS). Collagenase did not affect the staining pattern with commonly-used markers such as CD3, -4, -8, -19, -29, -45RO and -45RA. PMID- 1311738 TI - A comparative study of hemocytes from six different snails: morphology and functional aspects. AB - Hemocytes taken from six different gastropod snails, Achatina achatina, A. fulica, Biomphalaria glabrata, Bulinus natalensis, Helix aspersa, and Lymnaea stagnalis, were compared for morphology, peroxidase activity, and, using methods developed for L. stagnalis, the ability to generate reactive oxygen inermediates upon phagocytic stimulation. Numbers of hemocytes per milliliter hemolymph and hemocytes' microscopical morphology showed some variation among the snail species. Peroxidase activity was demonstrated in all snail hemocytes except in those of B. glabrata and A. fulica. Hemocytes of all species generated superoxide upon phagocytic stimulation with zymosan (tested by superoxide dismutase inhibitable reduction of nitroblue tetrazolium). When tested, hemocytes of A. achatina and of A. fulica displayed luminol-dependent chemiluminescence activity. PMID- 1311737 TI - A rapid limiting dilution assay for measuring frequencies of alloreactive, interleukin-2-producing T cells in humans. AB - A limiting dilution analysis (LDA) has been established which measures the total numbers of alloreactive interleukin-2 (IL-2)-secreting T cells in human peripheral blood mononuclear cells (PBMC). A significant advantage over most previous LDA is that the assay may be completed in approximately 48 h since an IL 2-dependent 'indicator' cell line is used to reduce assay time. Results are reproducible and correlate with the degree of HLA class II antigenic disparity between responder and stimulator cells. Use of both PBMC and Epstein-Barr virus transformed B lymphoblastoid cell lines (B-LCL) as stimulator cells permits estimation of the frequency of Epstein-Barr virus-specific T cells in different responder individuals. A modification of the assay may also be used to measure the frequencies of 'primed' alloreactive cells, i.e., those alloreactive cells which have previously encountered their specific stimulating alloantigen. Use of the assay in the clinical context of bone marrow and renal transplantation is discussed. PMID- 1311739 TI - Procainamide inhibits sympathetic nerve activity in rabbits. AB - Procainamide has been used extensively for the treatment of ventricular arrhythmias. It is widely held that the sympathetic nervous system plays an important role in the pathogenesis of ventricular arrhythmias. We investigated the possibility that procainamide has effects on the sympathetic nervous system by determining the responses to procainamide of postganglionic renal and preganglionic lumbar nerve activity in rabbits with sinoaortic and vagal denervation. Bolus administration of procainamide (3, 7, and 15 mg/kg) resulted in dose-dependent decreases in renal sympathetic nerve activity (26%, 38%, and 57%, respectively). These boluses resulted in plasma levels of procainamide of 13.3, 23.6, and 41.7 micrograms/ml, respectively. The same doses of procainamide resulted in decreases in lumbar nerve activity of 36%, 36%, and 41%, respectively. In a separate group of rabbits pretreated with hexamethonium (n = 8), 15 mg/kg procainamide reduced lumbar nerve traffic by 38%. Infusion of procainamide at 1 mg/kg/min over 20 minutes (n = 9) resulted in a decrease in renal sympathetic nerve activity of 20% with a plasma level of 11 micrograms/ml. Sham-treated rabbits (n = 8) exhibited an 18% increase in traffic over a comparable period of time. We conclude that procainamide inhibits lumbar and renal sympathetic nerve activity through effects on the brain or spinal cord. The influence of procainamide on sympathetic nerve activity may contribute importantly to its efficacy in the therapy of ventricular arrhythmias. PMID- 1311740 TI - Characterization of the ferritin receptors of human T lymphoid (MOLT-4) cells. AB - We have previously demonstrated that distinct binding sites exist for human recombinant H ferritin (HrHF) and human liver ferritin (HLF) on human T lymphoid cells (MOLT-4). This study demonstrates that these binding sites have the characteristics of receptors specific for HrHF, and the binding characteristics and internalization of HrHF to MOLT-4 cells have now been examined. Iodinated HrHF was displaced by an excess of unlabeled HrHF. Heavy ferritin was the major subunit bound with only a small amount of light-ferritin binding, consistent with our immunofluorescence studies. Scatchard plot analysis of the competitive binding data for HrHF revealed an association constant of 6.3 to 6.7 x 10(7) L/mol with approximately 6000 to 15,000 receptor sites per MOLT-4 cell. Internalization of HrHF was demonstrated with pronase. Chloroquine substantially reduced the uptake of HrHF. Release of internalized HrHF was not observed when cells were rewarmed to 37 degrees C. These results indicate that HrHF is internalized by a mechanism consistent with receptor-mediated endocytosis, with possible involvement of the lysosome. The internalized HrHF remains associated with the cell. Although lymphoid cell growth and differentiation were not examined in this study, the presence of the demonstrated receptors may indicate a regulatory role for heavy ferritin in such cells. PMID- 1311741 TI - A sensitive and specific erythropoietin immunoprecipitation assay: application to pharmacokinetic studies. AB - Previous pharmacokinetic studies with radiolabeled erythropoietin have relied on results of nonspecific methods to derive pharmacokinetic parameters. Dependence on nonspecific protein precipitation or total radioactivity may result in falsely high determinations of plasma radiolabeled erythropoietin and erroneous determinations of pharmacokinetic elimination and distribution parameters. In the present study pharmacokinetic parameters were derived by using a specific, sensitive, and reproducible immunoprecipitation assay for biologically active iodine 125-labeled recombinant human erythropoietin (125I-rhEp) and compared with those obtained by using nonspecific protein precipitation with trichloroacetic acid (TCA). Tracer amounts of 125I-rhEp were administered by bolus injection to six newborn lambs. Plasma-precipitable radioactivity assayed by the immunoprecipitation method became progressively lower with time relative to those observed with the TCA method. Pharmacokinetic parameters derived from the immunoprecipitation assay demonstrated significantly more rapid plasma and elimination clearances, shorter terminal half-life, shorter mean body residence time, and shorter distribution time when compared with the TCA assay (p less than 0.01). Volume of distribution was not different. Comparison of immunoprecipitation and TCA assay results from gel permeation fractions of iodinated erythropoietin demonstrated that immunoprecipitation assay results provide a better evaluation of biologically active hormone as determined by comparisons with SDS-PAGE and erythropoietin radioreceptor data. We conclude that 125I-rhEp pharmacokinetic parameters derived by using the immunoprecipitation assay more accurately reflect physiologic conditions than do those derived by using TCA precipitation. PMID- 1311742 TI - Characterization of erythropoietin production in a hepatocellular carcinoma cell line. AB - This study reports the effects of cyclic adenosine 3'-5' monophosphate (cAMP) and hypoxia on erythropoietin biosynthesis in an erythropoietin-producing hepatocellular carcinoma cell line (Hep3B). Erythropoietin levels in the medium and cell extracts of low-density Hep3B cells after 20-hour incubation under hypoxic conditions (1% O2) were 25.33 +/- 1.50 mU/ml/10(7) cells and 3.60 +/- 0.50 mU/10(7) cells, respectively. These levels were significantly higher than in the respective normoxic controls (medium, 2.51 +/- 0.31 mU/ml/10(7) cells; cell extracts, undetectable [less than 0.31 mU/10(7) cells]). Cobalt also produced a significant increase in medium and cell erythropoietin levels. However, hypoxia and cobalt alone failed to produce an increase in cAMP accumulation in the cell cultures. Erythropoietin levels in the medium and cell extracts from cells exposed to 8-bromo cAMP (1 x 10(-4) mol/L) and forskolin (4 x 10(-6) mol/L) in a hypoxic atmosphere were significantly (p less than 0.05) higher than in the respective hypoxic controls. In addition, forskolin produced a significant (p less than 0.05) increase in cAMP accumulation (180 +/- 11.5 pmol/10(6) cells) under hypoxic conditions compared with the hypoxic controls (cAMP, 2.27 +/- 0.33 pmol/10(6) cells). These results suggest that cAMP elevation is not required in vitro in Hep3B cells for the increase in medium and cell levels of erythropoietin after hypoxia, but may be involved indirectly in erythropoietin biosynthesis, secretion, or both in vivo through some synergistic action with hypoxia. PMID- 1311743 TI - Ossifying pleomorphic adenoma of the maxillary antrum. AB - An unusual case of pleomorphic adenoma with exuberant bone formation, occurring in the maxillary antrum of a 21-year-old male and showing repeated recurrence, is reported. In contrast to the endochondral ossification in the previous reported cases of pleomorphic adenoma, direct deposition of osteoid by metaplastic myoepithelial cells is suggested to explain the bone formation. The difficulties of distinguishing this tumour from osteosarcoma during intraoperative diagnosis are discussed. PMID- 1311744 TI - Anomalous features of human neutrophil activation by influenza A virus are shared by related viruses and sialic acid-binding lectins. AB - Influenza A virus (IAV) causes both activation and deactivation of the human neutrophil, which may, respectively, contribute to host defense against the virus and enhanced susceptibility to bacterial superinfection. We have shown that certain features of neutrophil activation by IAV are distinctive compared with activation by chemoattractants in terms of both the stoichiometry of the respiratory burst response and the signal transduction events that precede it. We here demonstrate that related myxoviruses as well as sialic acid-binding lectins elicit a respiratory burst response similar to that induced by IAV, in which hydrogen peroxide is formed with minimal accompanying superoxide generation. Brief preincubation of neutrophils with these agents fully inhibits subsequent activation by IAV, implying that they are binding to the same surface membrane components as IAV. Preincubation with Limax flavus agglutinin (LFA) does, in fact, substantially reduce binding of radiolabeled IAV to the neutrophil. This lectin, like IAV, both activates and deactivates the neutrophil. As in the case of IAV, LFA-induced activation (1) is mediated via stimulation of phospholipase C, (2) is pertussis toxin insensitive, and (3) entails a lesser contribution of calcium influx than is the case for chemoattractants. PMID- 1311746 TI - Fc receptor expression, concanavalin A capping, and enzyme content of bovine neonatal neutrophils: a comparative study with adult cattle. AB - The increased susceptibility of newborns to infection may in part be related to impaired in vitro functions of neonatal polymorphonuclear neutrophils (PMNs). To evaluate early steps in the activation cycle of bovine PMNs we determined the expression of Fc receptors (FcRs) with an erythrocyte rosetting assay utilizing bovine anti-sheep immunoglobulin G2 IgG2 and the accumulation of ligand receptor complexes or "caps" with fluorochrome-coupled concanavalin A (Con A caps) on neutrophils from adult (A-PMN) and newborn (N-PMN) bovines. In addition, the levels of myeloperoxidase (MPO) and alkaline phosphatase (AP) were determined. FcR expression is reduced in N-PMNs (P less than .001), in contrast to results observed with human N-PMNs. Basal capping of Con A binding sites is reduced (P less than .05) in N-PMNs but is enhanced (P less than .001) upon pretreatment with colchicine (0.5, 5.0, and 50.0 microns). These findings are again contrary to results observed with human N-PMNs. Consistent with findings in human neonates, however, are reduced levels of cellular MPO (P less than .05) and elevated cellular AP (P less than .001) in the neonate. The functional significance of elevated AP levels and altered Con A capping in N-PMNs is unclear. However, diminished expression of FcR could potentially contribute to impaired adherence and phagocytosis of bacteria, and reduced activity of neutrophil MPO could indicate weaker microbicidal capacity of neonatal cells. The demonstrated impairment of N-PMN functions could potentially contribute to reducing the effectiveness of the cellular host defense system in neonatal calves. PMID- 1311745 TI - Urokinase expression in mononuclear phagocytes: cytokine-specific modulation by interferon-gamma and tumor necrosis factor-alpha. AB - This study delineates the regulatory effects of inflammatory cytokines on mononuclear phagocyte plasminogen activator (PA) activity. The mechanisms by which mononuclear phagocytes modulate PA activity are described. Mononuclear phagocytes regulate net PA activity by the balanced expression of urokinase-type PA (uPA), in either secreted or membrane-associated forms, and a specific plasminogen activator inhibitor, PAI-2. Therefore, understanding how immunomodulators regulate macrophage PA activity requires that the comparative effects of uPA and PAI-2 be elucidated. We determine how recombinant interferon gamma (IFN) and tumor necrosis factor-alpha (TNF) regulate plasminogen activation in monoblast-like U937 cells and normal human monocytes. In U937 cells, both IFN and TNF induced concurrent increases in secreted PA and PA inhibitor activities. These effects were accompanied by increased immunoreactive uPA and PAI-2 in conditioned media (enzyme-linked immunosorbent assay) and steady-state levels of cellular uPA and PAI-2 mRNA (Northern analysis). To determine the relative abilities of IFN and TNF to either promote or inhibit plasmin generation, we directly compared the effects IFN and TNF, using optimal stimulating concentrations. IFN induced PA activity to 180% of the level achieved by TNF. In contrast, IFN elicited only 78% of the PA inhibitor produced by TNF stimulation. These differences in secreted activity can be explained by the shift in balance between uPA and PAI-2 proteins. Immunoreactive uPA was induced equally by IFN and TNF, but TNF generated higher levels of PAI-2. The same overall pattern of results was seen in normal human monocytes. IFN and TNF differ greatly in the ability to augment receptor-bound PA activity in U937 cells, as IFN induced a twofold increase but TNF had no effect. We conclude that IFN and TNF modulate mononuclear phagocyte proteolytic activity through coordinate regulation of secreted and receptor-bound uPA, balanced against concurrent expression of PAI-2. These effects are cytokine specific, as IFN is superior to TNF in stimulating expression of both secreted and receptor-associated PA activities. These properties suggest mechanisms by which mononuclear phagocytes control proteolysis in cytokine-rich inflammatory foci. PMID- 1311747 TI - Characterization of chicken lung angiotensin I-converting enzyme. AB - Angiotensin I(AI)-converting enzyme (ACE) (EC 3.4.15.1) was solubilized from the membrane fraction of chicken lung using trypsin and nonidet P40 extraction, and then purified to homogeneity by captopril affinity chromatography. Comparison of trypsin-extracted and detergent-solubilized membrane-bound converting enzyme by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectric focusing indicated that the membrane-binding sequence contributed to a large extent to the size and charge of the enzyme. Both forms of the enzyme were glycoproteins but they differed in the glucidic content; 4.5% by weight of the enzyme in the trypsin-extracted ACE and 15% by weight of the enzyme in the detergent-solubilized ACE. In both cases hexoses were the most abundant residues. Both forms of the enzyme were found to contain 1 g-atom zinc/mol enzyme. The purified enzymes did not only split Hip-His-Leu but also AI and bradykinin. The Michaelis constant (Km) and maximum velocity (Vmax) values of the trypsin extracted ACE for Hip-His-Leu were 52 x 10(-5) mol/l and 15.36 nmol/min respectively, and for AI they were 7.8 x 10(-5) mol/l and 0.45 nmol/min respectively. The Km and Vmax values of the detergent-solubilized ACE for Hip-His Leu were 32 x 10(-5) mol/l and 11.75 nmol/min respectively, and for AI they were 6.5 x 10(-5) mol/l and 0.97 nmol/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311748 TI - Effects of C19 steroids on adrenal steroidogenic enzyme activities and their mRNA levels in guinea-pig fasciculata-glomerulosa cells in primary culture. AB - The present study examined the effects of steroids on steroidogenic enzyme activity in adrenal glands. Guinea-pig fasciculata-glomerulosa (FG) cells maintained in primary culture were exposed to steroids for 48 h. Although the treatment with androstenedione alone had no effect on 3 beta-hydroxysteroid dehydrogenase 4-ene-5-ene-isomerase (3 beta-HSD), 17-hydroxylase and 17,20-lyase activities, there was inhibition of 11-hydroxylase and 21-hydroxylase activities. When FG cells were exposed to 10 nmol ACTH/l for the last 24 h of incubation, ACTH alone had no effect on steroidogenic enzymes but, while combined with androstenedione, it further decreased 21-hydroxylase activity and stimulated 17 hydroxylase and 17,20-lyase activities. Cortisol, corticosterone, oestradiol and 11 beta-hydroxy androstenedione had no effect on steroidogenic enzyme activities while the inhibitory effect on 21-hydroxylase activity was only observed with androstenedione, testosterone and dihydrotestosterone. Addition of hydroxyflutamide, a pure antiandrogen, did not block the inhibitory effect of androstenedione on 21-hydroxylase and 11-hydroxylase activities. The reduction in oxygen tension from 19 to 2% which was aimed at examining the oxygen-mediated effects on steroidogenic enzymes, revealed that the reduction in 21-hydroxylase activity induced by androstenedione could not be prevented by low oxygen tension. An interaction of C19 steroids at the level of the enzymes is also suggested by our finding that androstenedione had no effect on basal and ACTH-stimulated steady-state 11-hydroxylase, 17-hydroxylase, 17,20-lyase and 21-hydroxylase mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311749 TI - Growth hormone stimulates granulation tissue formation and insulin-like growth factor-I gene expression in wound chambers in the rat. AB - It has been reported that GH stimulates fibroblast growth and wound healing. In the present study we measured the effect of locally applied GH on insulin-like growth factor (IGF-I) mRNA concentrations and granulation tissue formation in wound cylinders, implanted s.c. Four stainless-steel wiremesh cylinders were implanted s.c. in the back of male rats (280 g). Each cylinder was then injected every day with either 0.014 or 0.14 U human GH, or vehicle only. Ingrown granulation tissue and wound fluid was obtained on day 17 after implantation. The wet weight of granulation tissue was determined and concentrations of IGF-I mRNA in the tissue were measured by solution hybridization/RNAase protection assay. Similar assays were used to measure the levels of IGF-I receptor mRNA and GH receptor mRNA, while the IGF-I concentration in wound fluid and serum was determined by radioimmunoassay (RIA) after acid-ethanol extraction. The concentrations of IGF-I mRNA in ingrown granulation tissue as well as the wet weight of this tissue were significantly higher in the GH-treated cylinders. There was no significant effect of GH on IGF-I receptor mRNA and GH receptor mRNA levels. Consistent with the results of previous studies, wound fluid IGF-I levels were lower than serum IGF-I levels, but no significant difference was found between the GH-treated cylinders and the control cylinders. The results of the present study show that GH stimulates granulation tissue formation and increases the concentration of IGF-I mRNA in the ingrown granulation tissue. PMID- 1311750 TI - Immunolocalization of mineralocorticoid receptor in human kidney, pancreas, salivary, mammary and sweat glands: a light and electron microscopic immunohistochemical study. AB - Using a polyclonal antibody against a synthetic fusion protein corresponding to 167 amino acids of the N-terminal region of the human renal mineralocorticoid receptor (MR), an immunohistochemical study was performed to investigate the intraglandular and intracellular localization of the receptor in human kidney, salivary gland, pancreas, mammary gland and sweat gland both at the light and electron microscopic levels. In the kidney, immunoreactivity was observed in distal convoluted tubules, branches of Henle's loop, and collecting tubules in the renal cortex, and papillary and Henle's loops' ducts in the renal medulla. No significant differences in the distribution of immunoreactivity were observed using different fixatives (10% neutral formalin, 100% methanol, 4% paraformaldehyde, PLP (periodate-lysine-2% paraformaldehyde) solution and Zamboni solution) and processing methods (paraffin embedding and frozen sectioning). Immunoreactivity in the kidney was observed in both the cytoplasm and nucleus, with cytoplasmic staining predominant, regardless of the methods of tissue preparation. Immunoelectron microscopy, employing a pre-embedding method, demonstrated the presence of immunoreaction precipitates in nuclei, endoplasmic reticulum, perinuclear cisternae, free cytoplasm and cell membranes. In nuclei, immunoreactivity was observed in euchromatin but not in heterochromatin, which is consistent with an association of MR with specific DNA regulatory elements located in transcriptionally active euchromatin. In other organs, MR was expressed in cells of the excretory ductal system where mineralocorticoids are known to play a role in electrolyte homeostasis. PMID- 1311751 TI - Clostridium botulinum toxins: a general review of involvement in disease, structure, mode of action and preparation for clinical use. AB - The neurotoxins produced by Clostridium botulinum are the most potent acute toxins known and are the causative agents of the neuroparalytic disease botulism. The toxins act primarily at peripheral cholinergic synapses by blocking the evoked release of the neurotransmitter acetylcholine. There are seven distinct serotypes of toxin. All are polypeptides of Mr about 150 kDa that have similar structure and pharmacological action. In their most active forms the toxins exist as dichain molecules in which a heavy (H) chain is linked by disulphide bonding to a light (L) chain. The H chain is believed to be associated with the highly specific and avid binding of toxin to the motor nerve end plates and also with the process of internalisation of the toxin. The toxic activity appears to be associated with the L chain which blockades the calcium-mediated release of acetylcholine, probably by interfering at the molecular level with the mechanisms whereby neurotransmitter-containing vesicles merge with the plasmalemma. The type A toxin is now used therapeutically to treat a variety of conditions involving involuntary muscle spasm. The therapeutic toxin is a neurotoxin-haemagglutinin complex isolated from cultures of C. botulinum. A controlled manufacturing process has been developed for the therapeutic toxin which is specially formulated to give a freeze-dried product having good stability. PMID- 1311752 TI - Fluctuation of serum phenytoin concentrations during autologous bone marrow transplant for primary central nervous system tumors. AB - We reviewed our experience for adult patients receiving oral anticonvulsant therapy during high-dose chemotherapy and autologous bone marrow re-infusion for primary malignant tumors of the central nervous system. Nineteen patients received either iv carmustine (BCNU) 900-1050 mg/m2 and 6120 cGy cranial irradiation (N = 10), iv carmustine 900-1050 mg/m2 and iv cisplatin 200 mg/m2 (N = 8), or iv carmustine 600 mg/m2, iv cisplatin 200 mg/m2, and iv etoposide 2400 mg/m2 (N = 1). Anticonvulsant therapy consisted of phenytoin alone (N = 8), phenobarbital alone (N = 4), carbamazepine alone (N = 2), phenytoin and carbamazepine (N = 2), carbamazepine and phenobarbital (N = 1), and no anticonvulsant therapy (N = 2). Serum anticonvulsant concentrations were monitored frequently and doses adjusted to keep values in the therapeutic range. While phenobarbital and carbamazepine doses remained relatively stable, all patients required increased doses of phenytoin anticonvulsant therapy after beginning chemotherapy (mean onset 3.7 days after initiation of chemotherapy). The increase in phenytoin dose ranged from 50% to 300% above baseline (mean 134%). By the time of discharge from the hospital (approximately 3-4 weeks after the start of chemotherapy) anticonvulsant dose was decreased to near pre-therapy levels. These swings coincided with the initiation of dexamethasone therapy for antiemetic effect and were more pronounced in patients also receiving cisplatin therapy. Due to close monitoring of serum phenytoin concentrations, no instances of toxicity due to excessive drug concentration, or seizures due to subtherapeutic doses, were noted in patients with primary CNS malignancies. Serum phenytoin concentrations fluctuate markedly during high-dose chemotherapy and must be analyzed frequently during the course of therapy. PMID- 1311753 TI - Iron absorption from bread in humans: inhibiting effects of cereal fiber, phytate and inositol phosphates with different numbers of phosphate groups. AB - Iron absorption was measured from five kinds of bread made from various types of flour and fermented in different ways in order to obtain a wide variation in the content of fiber, phytate (inositol hexaphosphate) and its degradation products, inorganic phosphate and inositol phosphates with fewer numbers of phosphate groups (inositol pentaphosphate through monophosphate). Each experiment had 9-10 subjects and, in each subject, iron absorption was measured from control rolls made from low extraction wheat flour and one kind of test roll using two different radioiron tracers: 55Fe and 59Fe. The inhibition of iron absorption was closely related to the content of phytate-phosphorous as determined using the AOAC method, and to the sum of the tri- through hexaphosphate groups as determined using the HPLC method. As an example, prolonged fermentation of whole rye bread reduced total inositol phosphates to the same amount as in the control rolls and increased fractional iron absorption to the same high level, in spite of a fiber content five times as great. The results strongly suggest that the inhibitory effect of bran on iron absorption is due to its content of phytate and other inositol phosphates present after fermentation, rather than to its content of fiber or other constituents. Thus, effective fermentation will increase the bioavailability of iron in whole-meal bread. PMID- 1311754 TI - Bile acid metabolism in rats fed two levels of corn oil and brans of oat, rye and barley and sugar beet fiber. AB - High concentrations of fecal bile acids are associated with a higher incidence of colon cancer. Dietary changes that alter bile acid metabolism are therefore of interest. Here, we report the effect of feeding diets containing four fiber sources and two fat levels for 7 wk on bile acid excretion and small intestinal bile acids (an index of pool size) in rats. The fiber sources were oat bran, rye bran, barley bran and sugar beet fiber. Fiber-containing diets were 8% dietary fiber and contained either 5 or 20% corn oil. All fiber sources caused significantly greater fecal output compared with the fiber-free basal diet. All fiber sources also resulted in significantly (P less than 0.05) lower fecal bile acid concentration compared with the fiber-free basal diet. Only rye bran resulted in significantly (P less than 0.05) higher total fecal bile acid excretion. Oat bran resulted in a slightly but significantly (P less than 0.05) higher quantity of small intestine bile acids compared with the other diets. Dietary fat level had no significant effect on fecal bile acid concentration or excretion or quantity of small intestinal bile acids. We conclude that all four fiber sources tested resulted in lower fecal bile acid concentration, by effectively causing greater fecal mass. Changes in dietary fat level as corn oil had no effect on fecal bile acids. PMID- 1311755 TI - Cholesterol-lowering in hamsters fed rice bran at various levels, defatted rice bran and rice bran oil. AB - This study was conducted to determine the relative cholesterol-lowering effects of several levels of full-fat rice bran in hamsters. In addition, the separate effects of defatted rice bran and/or crude rice bran oil were investigated at levels equivalent to those present in 43.7% full-fat rice bran. Diets containing 10.9, 21.8, 32.8 or 43.7% full-fat rice bran, 35% defatted rice bran and/or 9% rice bran oil were fed to 4-wk-old male hamsters. All diets contained 10% total dietary fiber, 9% fat and 3.2% nitrogen; hypercholesterolemic diets contained 0.3% cholesterol; two diets were cholesterol-free, i.e., 10% cellulose and 43.7% full-fat rice bran. After 21 d, plasma and liver cholesterol, plasma triglycerides and liver weights were significantly greater in hamsters fed the 10% cellulose diet with 0.3% cholesterol compared with those fed the cholesterol free cellulose diet. In animals fed cholesterol-free diets, plasma cholesterol values were significantly lower in those fed the 43.7% full-fat rice bran diet than in those fed the cellulose diet. In animals fed cholesterol-containing diets, plasma and liver cholesterol were significantly lower in animals fed the 43.7% full-fat rice bran diet than in those fed the cellulose diet. Plasma cholesterol reductions were significantly correlated to the level of rice bran in the diet. In cholesterol-fed hamsters, total liver cholesterol content was significantly lower in those fed the defatted rice bran diet with rice bran oil compared with those fed the cellulose diet. Full-fat rice bran was the only treatment that significantly lowered both plasma and liver cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311756 TI - Intestinal calcium transport and calcium extrusion processes at the basolateral membrane. AB - The intestinal absorption of calcium has been proposed to occur by the transcellular transfer of Ca2+ through the enterocyte proper and between the cells of the intestinal epithelium, i.e., the paracellular path. Attention in this report is given to the transcellular models of Ca2+ absorption and, more specifically, the Ca2+ extrusion events occurring at the basolateral membrane. These extrusion processes include the operation of an ATP-dependent Ca2+ pump and a Na+/Ca2+ exchanger, as well as exocytosis as the terminal event in a proposed vesicular transport mechanism. Evidence for the presence of an ATP-dependent Ca2+ pump at the basolateral membrane is documented and illustrated with biochemical and immunological data from studies on the avian intestinal basolateral membrane. As shown immunohistochemically, the Ca2+ pump was primarily localized on the enterocyte basolateral membrane. The ATP-dependency and vitamin D enhancement of Ca2+ uptake by isolated basolateral membrane vesicles are shown. Western blot analysis of intestinal mucosa, by using a monoclonal antibody produced against the erythrocyte Ca2+ pump, indicated that the number of pump units is increased by 1,25-dihydroxycholecalciferol. The possible involvement of calbindin-D28K as a direct stimulator of the Ca2+ pump is discussed, and the quantitative relationship between Ca2+ transport rates and Ca2+ pumping activity has been estimated. Information related to the basolateral membrane Na+/Ca2+ exchanger and the vesicular transport model of Ca2+ absorption is also briefly reviewed. PMID- 1311757 TI - A comparative study of the efficacy and morbidity of five techniques for ridge augmentation of the mandible. AB - Severely atrophic mandibles were augmented in 254 patients using five different surgical procedures, followed by total lowering of the floor of the mouth, vestibuloplasty, and skin graft. Patients were evaluated on a long-term basis to compare efficacy of treatment subjectively by recording patient complaints and by objectively assessing ridge form clinically and radiographically. Patients, in general, were pleased with the short- and long-term results of all five procedures. The ideal ridge form, comma-shaped, was obtained at a much higher rate with the three procedures using hydroxylapatite (HA) alone or in combination with collagen (HA-PFC). Ridge height loss both anteriorly and posteriorly was more severe in the two visor groups with bone graft or with HA than in those with only the alloplast. Labial sensory alterations more frequently occurred in the visor bone graft group, and wound dehiscence and lack of skin graft take were seen most often in the HA-PFC groups. Despite great differences in the quality of ridges obtained and in the number of complications between the visor groups and the alloplast groups, general patient satisfaction with any of the five procedures could be explained by the severity of the original complaints and because muscle interference has been eliminated in all cases by lowering of the floor of the mouth. PMID- 1311758 TI - Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature. AB - Centrally occurring salivary gland neoplasms of the jaws are rare. The clinical and histologic features of 11 cases including mucoepidermoid carcinoma, adenoid cystic carcinoma, and adenocarcinoma were reviewed. The patients ranged in age from 10 to 67 years, with a mean age of 45 years. Males and females were almost equally affected. Ten cases were intramandibular and 1 case was of maxillary origin. Eight of 11 tumors either were histologically associated with an odontogenic cyst, or there was some recent history of exodontia in the tumor area. A review of the pertinent literature yielded 127 previously reported centrally occurring primary salivary gland tumors arising within the maxilla and mandible. An analysis of these cases, their clinical and histologic characteristics, as well as a discussion regarding their probable histogenesis and new suggestions for clinical staging, has been included. PMID- 1311759 TI - Osseous response to implanted natural bone mineral and synthetic hydroxylapatite ceramic in the repair of experimental skull bone defects. AB - The purpose of this study was to assess and compare the osseous responses to implanted particles of resorbable anorganic xenograft bone mineral and non resorbable dense synthetic hydroxylapatite of two different granule sizes. Four trephine calvarial defects were produced in each of 13 adult rabbits. The experimental materials were subsequently implanted in three defects, leaving the fourth defect for control purposes. Six animals were killed 4 weeks after surgery and seven at 14 weeks. The tissue responses were assessed by contact radiography, light microscopy, and histometry. The biocompatibility of the implants was confirmed. All defects healed uneventfully, although the resorbable hydroxylapatite seemed to promote initial bone regeneration. The importance to orthognathic surgery of early and effective healing of bone gaps, as well as of the advantage of implant resorbability to bone remodeling, are discussed. PMID- 1311760 TI - The effect of therapeutic radiation on canine alveolar ridges augmented with hydroxylapatite. AB - The purpose of this investigation was to evaluate the effect of radiation on hydroxylapatite (HA) implanted subperiosteally for alveolar ridge augmentation in dogs. All bicuspids and molars were extracted from 16 dogs. After 6 weeks, nonporous HA granules were implanted subperiosteally on the alveolar ridge. Following 4 months of healing, 12 dogs (experimental group) underwent therapeutic radiation therapy (Co60, 4,000 rad [40 Gy]) to the head and neck region. Four dogs were not irradiated and served as controls. Four animals (three experimental and one control) were killed at 5,6,7, and 8 months after HA augmentation. Light microscopic evaluation showed that approximately 25% of HA granules were encased by bone while the others were surrounded by fibrous connective tissue. Dissolution of the HA was observed. Microparticles of HA were phagocytized as part of a granulomatous inflammatory reaction. This reaction decreased significantly as time elapsed after implantation. Osteoclastic activity was seen at the junction of HA and periosteum and as part of bone remodeling. Dissolution of the HA granules and the granulomatous inflammatory reaction were not significantly increased by therapeutic radiation. The radiation did not cause development of dehiscence or osteonecrosis. PMID- 1311761 TI - Detection of hepatitis C virus (HCV) RNA in paraffin embedded tissue sections of human liver of non-A, non-B hepatitis patients by in situ hybridization. AB - Localization of hepatitis C virus (HCV) RNA was investigated by non-radioactive in situ hybridization in human liver specimens of chronic non-A, non-B (NANB) hepatitis patients who were seropositive for antibodies to HCV (anti-HCV). For in situ hybridization, T-T dimerized synthetic oligodeoxynucleotide probes were used and DNAs hybridized in situ were detected immunohistochemically using specific antibodies against T-T dimer. The data demonstrates that HCV-RNA was localized in the cytoplasm of hepatocytes in human liver biopsies obtained from the patients with chronic NANB hepatitis seropositive for anti-HCV. PMID- 1311762 TI - Synthesis and structure-activity relationships of 7-diazabicycloalkylquinolones, including danofloxacin, a new quinolone antibacterial agent for veterinary medicine. AB - A series of novel 6-fluoro-7-diazabicycloalkylquinolonecarboxylic acids substituted with various C8 (H, F, Cl, N) and N1 (ethyl, cyclopropyl, vinyl, 2 fluoroethyl, 4-fluorophenyl, 2,4-difluorophenyl) substituents, as well as, 9 fluoro-10-diazabicycloalkylpyridobenzoxazinecarboxylic acids, were prepared and evaluated for antibacterial activity against a range of important veterinary pathogenic bacteria. The diazabicycloalkyl side chains investigated at the 7 position (benzoxazine 10-position) include (1S,4S)-5-methyl-2,5 diazabicyclo[2.2.1]heptane (2), (1S,4S)-2,5-diazabicyclo[2.2.1]heptane (3), (1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (4), 8-methyl-3,8 diazabicyclo[3.2.1]octane (5), 9-methyl-3,9-diazabicyclo[4.2.1]nonane (6), 1,4 diazabicyclo[3.2.2]nonane (7), 1,4-diazabicyclo[3.3.1]nonane (8), and 9-methyl 3,9-diazabicyclo[3.3.1]nonane (9). Among these side chains, in vitro potency was not highly variable; other properties therefore proved more critical to the selection of possible development candidates. However, the relative potencies observed for several of these compounds in mouse, swine, and cattle infection models correlated well with those seen in vitro. A combination of the N1 cyclopropyl group and the C7 (1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl appendage conferred the best overall antibacterial, physiochemical, and pharmacodynamic properties. Hence, danofloxacin (Advocin, 2c) (originally CP 76,136, 1-cyclopropyl-6-fluoro-7-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1] hept-2 yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid) was selected as a candidate for development as a therapeutic antibacterial agent for veterinary medicine. PMID- 1311764 TI - Systemic analgesic activity and delta-opioid selectivity in [2,6-dimethyl-Tyr1,D Pen2,D-Pen5]enkephalin. AB - The cyclic peptide [2,6-dimethyl-Tyr1,D-Pen2,D-Pen5]enkephalin (2) was synthesized by solid-phase techniques and contains the optically pure unnatural amino acid 2,6-dimethyltyrosine (DMT) as a replacement for the Tyr1 residue of [D Pen2,D-Pen5]enkephalin (DPDPE, 1). This structural modification resulted in a 10 fold increase in the potency of 2 at the delta opioid receptor and a 35-fold increase in potency at the mu receptor while substantial delta receptor selectivity was maintained. In addition, 2 was 86-fold more effective than 1 at inhibiting electrically stimulated contractions of the mouse vas deferens. In the hot plate test, 2 was 7-fold more potent than 1 after intracerebroventricular administration in the mouse. While 1 was inactive following systemic administration of doses as high as 30 mg/kg, subcutaneous administration of 2 significantly inhibited writhing with an ED50 of 2.6 mg/kg. These results demonstrate that the potency and systemic activity of DPDPE are significantly increased by replacement of Tyr1 with DMT. PMID- 1311763 TI - 3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase. AB - A series of 1H-imidazol-1-yl- and 3-pyridyl-substituted 3,4-dihydroquinolin-2(1H) ones was designed and synthesized as combined inhibitors of thromboxane (TXA2) synthase and cAMP phosphodiesterase (PDE) in human blood platelets. A number of structures, e.g. 4b, 7a, 7e, 13a, and 21-25, were superior to dazoxiben 26 as inhibitors of TXA2 synthase in in vitro ADP-induced aggregation experiments with human blood platelets. The TXA2 synthase inhibitory activity was confirmed by measurement of the prostanoid metabolites derived from 14C-labeled arachidonic acid. Three compounds (7a, 7e, and 25) demonstrated in vitro inhibition of human platelet cAMP PDE at micromolar concentrations in conjunction with their TXA2 synthase inhibitory activity. Synergistic enhancement of antiaggregatory and antithrombotic actions was expected when simultaneous stimulation of adenylate cyclase (through increased PGI2 production) and inhibition of platelet cAMP PDE were possible from the same compound. Ex vivo and in vivo experiments were conducted in rats and mice, respectively, to evaluate the effects of compounds 7e and 23 on platelet aggregation and thrombotic events within these animals. Compound 7e, which has a comparable level of TXA2 synthase (IC50 1.2 microM) and human platelet cAMP PDE (IC50 6.4 microM) inhibitory activities, was found to be orally bioavailable with a long duration of action and offered effective protection against mortality in a collagen-epinephrine-induced pulmonary thromboembolism model in mice. Significant blood pressure and heart rate effects were observed for several compounds, e.g. 7e, 9e, 13a, 13d, 18, 20, 21, and 23, when dosed orally in conscious spontaneously hypertensive rats. PMID- 1311765 TI - Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site. AB - We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presence of two pharmacophores: a 4'-aryl methyl ether and a basic substituent appended to N1 with a pKa in the physiological range. When these constraints are satisfied, a wide variety of substitution is tolerated at C6, C7, and C3. The presence of an electron-withdrawing group at C6 appears to enhance potency in vitro and in vivo. For such benzazepinones, activity is primarily dependent upon lipophilicity, as measured by log P. We believe these compounds must partition into the cell membrane in order to access their receptor. The quaternary methiodide 15k was used to demonstrate that the binding site for benzazepinones is on the intracellular face of the membrane. This work represents the first comprehensive SAR of diltiazem-like calcium channel blockers. PMID- 1311766 TI - Depolarization exposes the voltage sensor of the sodium channels to the extracellular region. AB - Two domains of Na channels were mapped with site-specific antibodies raised in rabbit against synthetic peptides corresponding to a part of the voltage sensor of internal repeat 1-C1+ (amino acids 210-223) and to a region designated dipole (amino acids 1690-1699) of eel electroplax sodium channels. The antibodies bind to their respective domains in both purified and membrane-bound channels and immunoprecipitate the channels from eel electroplax and rat brain synaptosomes. Anti-C1+ depresses the action potential of rat sciatic nerve in a concentration dependent way. It binds to the external side of rat brain synaptosomal vesicle, and its binding is potentiated by depolarization. Anti-dipole binds to the inner side of the vesicle, and the binding is inhibited by depolarization. PMID- 1311767 TI - Regulation of principal cell pH by Na/H exchange in rabbit cortical collecting tubule. AB - Changes in intracellular pH (pHi) were measured using the pH indicator, BCECF, in principal cells from split opened cortical collecting tubules (CCTs) derived from rabbits maintained on a normal diet. This monolayer preparation has the advantage of allowing us to visualize the morphological differences in the two major cell types in this nephron segment under transmitted light. The visual identification of the cell types was verified using emission measurements taken from single principal and intercalated cells in the opened tubule which had been exposed to fluorescein isothiocyanate (FITC)-labeled peanut lectin. We confirmed the existence of an amiloride-sensitive Na/H exchange process activated during intracellular acidosis in principal cells. In addition, the exchanger was active under basal conditions and over a wide range of pHi. Because the exchanger was active under basal conditions we tested the hypothesis that changes in intracellular Na (Nai) would alter pHi in a predictable way. Maneuvers designed to alter Nai were without significant effects within a 10-min time frame. Specifically, addition of 100 microM ouabain to increase Nai or exposure of the tubules to 10(-5) M amiloride to decrease luminal Na entry and reduce Nai did not have an effect on pHi. In some experiments we did observe however, after a 30-min exposure to ouabain, a small decrease in pHi. These results suggest that Na/H exchange is a major regulator of pHi in principal cells. However, regulation of Na transport by changes in pHi in principal cells of rabbit CCT via the activity of a Na/H exchanger do not seem to contribute to the feedback control of Na transport. PMID- 1311768 TI - Evidence that plasma membrane electrical potential is required for vesicular stomatitis virus infection of MDCK cells: a study using fluorescence measurements through polycarbonate supports. AB - We used fluorescence microscopy of Madin-Darby Canine Kidney (MDCK) cells grown on polycarbonate filters to study a possible link between plasma membrane electrical potential (delta psi pm) and infectivity of vesicular stomatitis virus (VSV). Complete substitution of K+ for extracellular Na+ blocks VSV infection of MDCK cells as well as baby hamster kidney (BHK) cells. When we independently perfused the apical and basal-lateral surfaces of high resistance monolayers, high K+ inhibited VSV infection of MDCK cells only when applied to the basal lateral side; high K+ applied apically had no effect on VSV infection. This morphological specificity correlates with a large decrease in delta psi pm of MDCK cells when high K+ buffer is perfused across the basal-lateral surface. Depolarization of the plasma membrane by 130 mM basal K+ causes a sustained increase of cytosol pH in MDCK cells from 7.3 to 7.5 as reported by the fluorescent dye BCECF. Depolarization also causes a transient increase of cytosol Ca2+ from 70 to 300 nM as reported by the dye Fura-2. Neither increase could explain the block of VSV infectivity by plasma membrane depolarization. One alternative hypothesis is that delta psi pm facilitates membrane translocation of viral macromolecules as previously described for colicins, mitochondrial import proteins, and proteins secreted by Escherichia coli. PMID- 1311769 TI - N-methyl-N-nitrosourea-induced mutations in human cells. Effects of the transcriptional activity of the target gene. AB - In this study we addressed the question as to whether the mutagenesis by methylating agents is affected by the transcriptional activity of the damaged gene. An Epstein-Barr virus (EBV)-derived shuttle vector system was developed where the genetic target for mutation analysis, the bacterial gpt gene, is under the control of an eukaryotic inducible promoter in plasmid pF1-EBV and lacks the eukaryotic promoter in plasmid pF2-EBV. Two human cell lines that episomically maintain these shuttle vectors were established. In clone 6NT cells, which contain pF1-EBV plasmid, the gpt gene is actively transcribed and the transcription rate is regulated by zinc ions. In clone 3 cells, which harbor pF2 EBV plasmid, the gpt gene is not transcribed. Following treatment of both cell lines with the potent alkylating carcinogen N-methyl-N-nitrosourea (MNU), G.C to A.T transitions were the major mutagenic event, consistent with the miscoding potential of O6-methylguanine. The mutations were predominantly generated in the non-transcribed DNA strand of the active gpt gene. The same strand-bias was observed when the gpt gene was transcriptionally inactive, indicating that MNU induced strand-specific formation of mutations is not due to transcription. Our data identify as major determinants of this phenomenon the sequence-specificity of MNU mutagenesis and the conformational properties of the target protein. Differences in mutation distribution were observed between the transcriptionally active and inactive gpt gene. This finding suggests that the organization of active genes in chromatin might modulate DNA alkylation and/or DNA repair. PMID- 1311770 TI - Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins. AB - Two crystal forms (P6(3) and R3) of human annexin V have been crystallographically refined at 2.3 A and 2.0 A resolution to R-values of 0.184 and 0.174, respectively, applying very tight stereochemical restraints with deviations from ideal geometry of 0.01 A and 2 degrees. The three independent molecules (2 in P6(3), 1 in R3) are similar, with deviations in C alpha positions of 0.6 A. The polypeptide chain of 320 amino acid residues is folded into a planar cyclic arrangement of four repeats. The repeats have similar structures of five alpha-helical segments wound into a right-handed compact superhelix. Three calcium ion sites in repeats I, II and IV and two lanthanum ion sites in repeat I have been found in the R3 crystals. They are located at the convex face of the molecule opposite the N terminus. Repeat III has a different conformation at this site and no calcium bound. The calcium sites are similar to the phospholipase A2 calcium-binding site, suggesting analogy also in phospholipid interaction. The center of the molecule is formed by a channel of polar charged residues, which also harbors a chain of ordered water molecules conserved in the different crystal forms. Comparison with amino acid sequences of other annexins shows a high degree of similarity between them. Long insertions are found only at the N termini. Most conserved are the residues forming the metal-binding sites and the polar channel. Annexins V and VII form voltage-gated calcium ion channels when bound to membranes in vitro. We suggest that annexins bind with their convex face to membranes, causing local disorder and permeability of the phospholipid bilayers. Annexins are Janus-faced proteins that face phospholipid and water and mediate calcium transport. PMID- 1311771 TI - Determination of the nuclear magnetic resonance solution structure of the DNA binding domain (residues 1 to 69) of the 434 repressor and comparison with the X ray crystal structure. AB - The DNA-binding domain of the phage 434 repressor consisting of N-terminal residues 1 to 69 (434 repressor(1-69)), was expressed in Escherichia coli with natural isotope abundance, uniform 15N-labeling and biosynthetically directed fractional 13C-labeling in extent of about 10%. With these protein preparations the three-dimensional structure was determined in solution. The techniques used were nuclear magnetic resonance (n.m.r.) spectroscopy for the collection of conformational constraints, calculation of the protein structure from the n.m.r. data with the program DIANA and structure refinements by restrained energy minimization with a modified version of the program AMBER. A group of 20 conformers characterizes a well-defined structure for residues 1 to 63, with an average of 0-6 A for the root-mean-square deviations (RMSD) calculated for the backbone atoms of the individual conformers relative to the mean co-ordinates. The spatial structure of C-terminal residues 64 to 69 is not defined by the n.m.r. data. The molecular architecture of the 434 repressor(1-69) in solution includes five alpha-helices extending from residues 2 to 13, 17 to 24, 28 to 35, 45 to 52 and 56 to 60, which enclose a well-defined hydrophobic core. The n.m.r. structure is closely similar to the reported crystal structure of the 434 repressor(1-69), with an RMSD value of 1.1 A for the backbone atoms of residues 1 to 63. Small differences between the two structures in regions of the first helix and the loop between helices 3 and 4 were analyzed relative to possible correlations with protein-protein contacts in the crystal lattice and the different milieus of pH and ionic strength in the crystals and n.m.r. samples. Further systematic comparisons of local conformational features indicated that there are correlations between amino acid types, local precision of the structure determination by both techniques and local differences between the structures in the crystals and in solution. Overall, hydrophobic residues are most precisely characterized and agree most closely in the two environments. PMID- 1311772 TI - Phase II trial design considerations for small-cell lung cancer. PMID- 1311773 TI - Proton beams in radiation therapy. AB - The rationale for study of proton radiation therapy is that, for some anatomic sites and tumors, the treatment volume is smaller; i.e., there is less irradiation of nontarget tissue while the target is included in three dimensions at each treatment session. As a result, the dose to the target can be raised. The consequence is that the tumor control probability improves and the frequency and severity of treatment-related morbidity decrease. These results come about from the physical fact that the proton range in tissue is finite; in comparison, absorption of photons is an exponential function and, hence, some dose is received for the full-beam path through the body. Accordingly, the dose deep to the target for proton treatments can be zero for each beam path. This situation provides a virtually certain means of improving the treatment outcome for selected categories of patients. Experience to date with proton radiation therapy has been quite limited. As of June 1991, the total number of proton radiation treated patients was 11,763 from the various centers. Of that number, approximately 46% and 32% have been treated for small benign intracranial lesions (principally pituitary adenomas and arteriovenous malformations) and for tumors of the eye, respectively. Thus, only some 2500 patients have been treated for all other tumor types. The results from three centers and approximately 2800 patients with uveal melanoma are that the local control rate was 96% (for failures in field, marginal, and in other parts of the eye). The local control results for chondrosarcomas and chordomas of the skull base are 91% and 65%, respectively. These percentages compare with some 35% achieved with conventional treatment. Experience with arteriovenous malformations indicates that control of bleeding and disappearance of the lesion are comparable to those achieved by other procedures. The developments from the proton therapy programs have contributed greatly to radiation treatment planning, e.g., the first three-dimensional treatment planning system put into regular clinical use (uveal melanoma), beam's eye view, digital-reconstructed radiograph, dose-volume histograms, and definitions of the uncertainty in dose around any defined point. The potential for clinical gains is high. In May 1991, the Proton Radiation Oncology Group was formed to design, supervise, and coordinate clinical trials and to assist in data analysis. The efficacy of proton radiation therapy will be compared with that of photon therapy of the very highest technology. PMID- 1311774 TI - RNA expression of the WT1 gene in Wilms' tumors in relation to histology. AB - BACKGROUND: On the basis of accumulating data, the recently isolated WT1 gene is a Wilms' tumor gene and a putative tumor suppressor gene. These findings include expression in developing fetal kidney, intragenic deletions in tumors, and germline mutations in predisposed individuals. Wilms' tumors, which exhibit a broad range of differentiation, are composed of three cell types: blastema, epithelium, and stroma. PURPOSE: The purpose of this study was to investigate the relationship between WT1 gene expression and histologic composition in Wilms' tumors in an effort to elucidate how the WT1 gene functions in proliferation of these histologic components. METHODS: We used Northern blot hybridization to study WT1 gene expression by messenger RNA (mRNA) accumulation in 20 tumors of varying histology and in adjacent uninvolved kidney tissue. In two patients, tumors were also compared before and after therapy. RESULTS: Tumors that were predominantly blastemal expressed high amounts of WT1 mRNA, whereas predominantly stromal tumors expressed either low or undetectable amounts. Blastemal tumors that were predominantly poorly differentiated expressed WT1 mRNA at higher levels than those that were more well differentiated. Although we expected that a putative tumor suppressor gene like WT1 would generally be expressed at lower levels in tumor than in normal kidney, this was true only in predominantly stromal cells. One of the two patients studied before and after therapy had a dramatic response to therapy accompanied by a decline in WT1 gene expression and disappearance of blastemal and epithelial elements. CONCLUSIONS: A correlation was observed between WT1 gene expression and histology of the tumors. Level of expression was inversely related to the degree of differentiation in blastemal tumors and in the patient with a dramatic response to therapy. These results, in conjunction with the observation that WT1 mRNA is abundant in normal fetal kidney, suggest that WT1 gene expression is related to kidney development, especially in differentiation of blastemal components. IMPLICATIONS: Further studies to search for alterations of the WT1 gene in tumors and to identify regulatory factors in gene expression will increase understanding of the role of this gene in normal development and tumorigenesis. PMID- 1311775 TI - Prevalence of human papillomavirus in young women. PMID- 1311776 TI - In vitro studies of the efficacy of reversed phase silica gel as a sorbent for hemo- and plasmaperfusion. AB - The clearance capacities of reversed phase silica gel, widely used in analytical chemistry, were studied in vitro. The plasma clearances of amitriptyline, quinidine, digoxin, digitoxin, methaqualone, phenobarbital and phenytoin were determined at typical toxic plasma levels. Between 88.8 and 99.5% of the drugs were eliminated from plasma by reversed phase silica gel, which compares favorably with amberlite XAD-4 and coated activated charcoal. The biocompatibility of reversed phase silica gel was also evaluated in vitro. Thrombocytopenia and leukopenia were noted while coagulation parameters, electrolytes, acid-base balance, glucose, urea, creatinine, uric acid, total protein, albumin, bilirubin, cholesterol and triglycerides were not significantly affected. Preliminary results in vitro support the high clearance capacity of reversed phase silica gel and suggest a biocompatibility similar to that of other sorbents currently in use. Further investigation of the clearance capacities and biocompatibility of reversed phase silica gel seems justified. PMID- 1311777 TI - From the Alcohol, Drug Abuse, and Mental Health Administration. PMID- 1311778 TI - Recent developments in the treatment of lung cancer. PMID- 1311779 TI - [Discovery and development of the proton pump inhibitor]. AB - Gastric (H+/K+)-ATPase, the proton pump of the parietal cell, is responsible for the final step of acid secretion in the stomach. In 1981, picoprazole, a substituted benzimidazole, was found to inhibit (H+/K+)-ATPase. It was reported in 1983 that omeprazole has the most potent efficacy among the substituted benzimidazoles and today, omeprazole has been used for treatment of gastroduodenal disease. Recently, lansoprazole, similar to omeprazole in chemical structure, was developed in Japan, and several other compounds, such as pantoprazole, E-3810 and NC-1300-O-3, have also been reported to suppress acid secretion through inhibition of (H+/K+)-ATPase. In the present paper the background of the discovery of (H+/K+)-ATPase and development of proton pump inhibitors is reviewed. PMID- 1311780 TI - [Clinical effect of proton pump inhibitors on reflux esophagitis]. AB - The clinical efficacy of proton pump inhibitors (PPI, omeprazole 20 mg or lansoprazole 30 mg), once daily, after breakfast, was studied in patients with erosive/ulcerative reflux esophagitis. The following results were obtained. 1) Twenty-four hour esophageal pH monitoring was performed before treatment and on 7th day of PPI medications. Omeprazole reduced the percent time pH less than 4 from 29.1 to 1.2 and lansoprazole from 68.0 to 2.4. 2) The cumulative disappearance rate of overall symptom was 52% after 1 week and 62% after 2 weeks with omeprazole these were 66% and 91%, and with lansoprazole respectively 3) The endoscopic healing rate was 63% was after 2 weeks and 76% after 4 weeks with omeprazole medication, and 76% and 97% respectively with lansoprazole. These results indicate that PPI medication inhibits the acid reflux almost completely and is a more useful therapeutic agent for GERD than H2-antagonists. PMID- 1311781 TI - [Recurrent peptic ulcer after gastric surgery]. AB - Recurrent peptic ulcer after gastric surgery differs from duodenal ulcer in that they usually occur with low acid output, which is sufficient to cause ulceration in predisposed stomach or anastomosis. The proton pump inhibitor (PPI), significantly more potent and long-acting than H2-blocker, is expected to be more effective for postoperative recurrent ulcers. We evaluated the efficacy of omeprazole (OPZ) on recurrent ulcers in 12 patients following either gastrectomy or vagotomy. The healing rate after 4 week treatment with OPZ was 58% and increased to 100% after 8 week. Evaluation of quick symptom relief also supported the efficacy of OPZ treatment. These findings showed that OPZ treatment resulted in a more rapid healing of recurrent ulcers compared with H2-blocker. It remains to be clarified whether quit of treatment with PPI would induce high ulcer relapse rates, and whether maintenance therapy with PPI would be the only alternative therapy for surgical intervention. PMID- 1311782 TI - [Proton pump inhibitor for maintenance therapy of peptic ulcer]. AB - The strategy for peptic ulcer therapy has been changing with the clinical application of the gastric proton pump inhibitor (PPI). In Japan, Miyoshi et al and Takemoto et al reported an earlier reepithelialization of peptic ulcer with omeprazole (OME) or lansoprazole (LAN) than famotidine (FAM). Miyoshi et al also reported that there was no significant difference between OME and FAM in ulcer relapse rate during a one year follow-up period. Therefore, there were two problems. One is application of PPI for prevention of ulcer relapse, and the other is the more accurate diagnosis of ulcer healing. Application of PPI for maintenance therapy is not yet realized in Japan, but, Lauritsen et al had already reported on the efficacy and safety of OME, 20 mg, three days a week and 10 mg, daily in prevention of duodenal ulcer relapse. Reepithelialization (red scar) is already established as a starting point of maintenance therapy, and from Miyake's report, a white scar is believed a favorable (non relapsing) end point. PMID- 1311783 TI - [Studies on the intracellular pharmacodynamic properties of proton pump inhibitors and the inhibitory mechanism of acid secretion]. AB - In recent studies, proton pump inhibitors, such as omeprazole, were found to be transformed into sulfenamide derivatives in the acid space of isolated parietal cells. It is considered that these sulfenamide derivatives mainly inhibit H+, K(+)-ATPase activity. To clarify the inhibitory mechanism of proton pump inhibitors, we studied the effect on acid secretion of the isolated parietal cells. Proton pump inhibitors inhibited histamine-, carbachol- and gastrin stimulated 14C-aminopyrine accumulation. Db-cAMP stimulation was also inhibited by these inhibitors. Consequently, it is believed that the origin of H+, K(+) ATPase was located in the final stage of the acid production. PMID- 1311784 TI - [Treatment of gastric ulcers with proton pump inhibitors--long-term treatment]. AB - Pronounced inhibition of acid secretion appears to induce an intragastric environment suitable for N-nitrosamine formation, hyper-gastrinemia, ECL cell hyperplasia and carcinoid tumor formation. Development of gastric cancer, however, has not been obvious in clinical and experimental studies, but oncongenicity studies indicate an increased risk of gastric cancer with long-term use of proton pump inhibitors in subjects with hyperplastic or other, changes in the gastric mucosa. The findings suggest that proton pump inhibitors should be used only for short term treatment. PMID- 1311785 TI - [Changes in the rat stomach after long-term administration of proton pump inhibitors (AG-1749 and E-3810)]. AB - E-3810 and AG-1749, new proton pump inhibitors, were administrated in single doses or over a long period of time in order to evaluate their effect on the rat stomach. E-3810 inhibited gastric acid secretion for a shorter period of time than AG-1749 in both the single dose and long-term administration. While hypergastrinemia persisted with long-term administration of AG-1749, serum gastrin levels returned to normal upon cessation of treatment with E-3810. Both E 3810 and AG-1749 caused vacuolar formation of parietal cells and an increase in gastric acid secretion after cessation of long-term treatment, suggesting that these changes are common after treatment with proton pump inhibitors. PMID- 1311786 TI - [Possible mechanisms for (H+ + K+)-ATPase inhibition by proton pump inhibitors, omeprazole, lansoprazole and SCH 28080]. AB - Proton pump inhibitors are classified into two distinct types, and the mechanisms are reviewed. Substituted benzimidazole such as omeprazole and lansorrazole, inhibit (H+ + K+)-ATPase by reacting with SH groups of enzyme after the drugs are transformed into their active forms in the acidic environment of the intracellular canaliculi of parietal cells. This type of enzyme inhibition results in potent and long-lasting inhibition of gastric acid secretion. On the other hand, substituted imidazo pyridines, such as SCH 28080, inhibit (H+ + K+) ATPase by competing with K+. This inhibition is reversible and the antisecretory effect is short-lived. Recent studies on DNA cloning and sequencing for (H+ + K+) ATPase have led to a better understanding of enzyme structure and also the sites of action of the proton pump inhibitors. PMID- 1311787 TI - [Protective effect of proton pump inhibitor on the gastric mucosa]. AB - Although many authors reported that proton pump inhibitor showed mucosal protective activity, the precise mechanism is still unclear. In this study, we investigated the effect of proton pump inhibit on gastric mucosal hemodynamics, using a reflectance spectrophotometry system. The proton pump inhibitors had no effect on the gastric mucosal hemodynamics prior to the state of hemorrhagic shock state. However, during the hemorrhagic shock, proton pump inhibitors significantly inhibited the decrease in tissue oxygenation and significantly reduced ulcer formation. In conclusion, proton pump inhibitors maintained tissue oxygenation resulting in reduction of ulcer formation. PMID- 1311788 TI - [Effect of proton pump inhibitor, in combination with epidermal growth factor, on the healing of chronic gastric ulcer in submandibular gland removed rats]. AB - The effect of a proton pump inhibitor, omeprazole (OPZ), in combination with mouse epidermal growth factor (EGF), on the healing of chronic gastric ulcers induced by acetic acid in submandibular glands removed rats (SMR rat) was investigated. Four separate groups of SMR rats were orally administered 1 ml of distilled water (control), 100 mg/kg of OPZ alone (OPZ), 5 micrograms/kg of mouse EGF alone (EGF), or combination with (EGF + OPZ) twice daily. Two weeks later, ulcer areas of four groups were measured and expressed as the ulcer index (UI). The UI of the OPZ and EGF + OPZ group was significantly reduced as compared with that of the control. Furthermore, the UI of the EGF + OPZ group was significantly smaller than that of the EGF group. The present study indicates that the proton pump inhibitor promotes healing of chronic gastric ulcers in SMR rats and the effect of the proton pump inhibitor is enhanced by administration of mouse EGF. PMID- 1311789 TI - [Characteristic features of proton pump inhibitors in the inhibition of gastric acid secretion: long-acting and complete inhibition]. AB - Proton pump inhibitor is a compound recently applied for the treatment of peptic ulcers for its strong action to inhibit the gastric acid secretion. It works through inhibition of H+, K(+)-ATPase, so called proton pump, on the luminal surface of secretory canaliculi in the parietal cells, showing remarkable characteristics in the inhibition of gastric acid secretion; e.g., the long acting and complete inhibition. At neutral pH, the unionized form of this compound as a weak base is lipophilic, and passes through the cell membrane to accumulate as the ionized form in an acidic environment in the secretory canaliculi of parietal cells, where it is transformed to an active molecule which binds covalently to the active site of H+, K(+)-ATPase, forming a highly stable complex. The long-acting and complete inhibition of gastric acid secretion by this compound is derived from this physico-chemical nature. The above characteristics of the proton pump inhibitor have been confirmed with the basal, stimulated and nocturnal gastric acid secretion and the 24-hour intragastric pH of healthy volunteers by several investigators prior to its nation-wide clinical trial in Japan. On the other hand, the increased endocrine and exocrine secretion, such as pepsin secretion and gastrin release, and the increased turnover of gastrointestinal endocrine cells by this compound have been reported in animal models, probably due to its accumulation in the acidic environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311790 TI - [Magnifying endoscopic observation on the effect of a proton pump inhibitor on the healing process of gastric ulcer]. AB - The effect of a proton pump inhibitor on the healing process of gastric ulcer was investigated through magnifying endoscopic observation of the regenerated mucosa. The findings were the same obtained as those by stereoscopic microscopic observation of the effect of conventional drugs. Namely, a structureless red area consisting of one layer of regenerated epithelium was the first to procede forward the ulcer base, and a radially arranged roughly striated pattern of regenerated mucosa, in which gastric glands were formed. The regenerated mucosa changed from a striated to a granular pattern. In a shallow ulcer, the ulcer scar showed a fine gastric mucosal pattern similar to that of the surrounding area. The strong inhibition of gastric acid secretion by a proton pump inhibitor is believed to raise no problems in the healing process of peptic ulcer. The magnifying endoscopic observation also disclosed that the protruding granulation disappeared gradually and changed to concave regenerated epithelium, suggesting that the ulcer base protrusion, which has been considered as an adverse effect of strong acid secretion inhibitors, has no influence on the healing of the ulcer. PMID- 1311791 TI - [Evaluation of chromo-endoscopy for diagnosis of histological repair of gastric ulcer]. AB - The chromoendoscopic features of healed gastric ulcers were investigated by the methylene blue test. Histological repair of healed ulcers was graded as either Ul3 (incompletely healed) or Ul4 (completely healed). Endoscopically, the Ul4 scar was observed as a flat granular area without any depression, and sometimes associated with redness, the Ul3 scar was observed as a distinct depression in the surrounding normal mucosal surface, and usually associated with homogenous redness. Follow-up studies of patients with Ul4 and Ul3 lesions showed that recurrence was significantly rare in patients with the Ul4 lesion than in patients with the Ul3 lesions. These findings indicate that healing of gastric ulcers should be defined endoscopically as crater disappearance. At 8 weeks after treatment with omepral, most of the ulcers were healed, but judged a as Ul3 scar. PMID- 1311792 TI - Bradykinin-induced biphasic response in the rat isolated stomach fundus: functional evidence for a novel bradykinin receptor. AB - The responses of the rat isolated stomach fundus to bradykinin (BK) and des-Arg9 BK (DA-BK) have been examined. In rat isolated stomach fundus pre-contracted with BaCl2 (0.5-1 mM), BK caused concentration-dependent biphasic responses characterized by relaxation followed by contraction. DA-BK also caused marked relaxations, but, unlike BK, induced only small contractions. Removal of the mucosal layer initially abolished the relaxant responses to BK and both responses to DA-BK without affecting BK-induced contractions, but repeated challenges with BK or DA-BK revealed a time-dependent reappearance of the relaxant response, suggesting "de novo" synthesis of BK receptors. Pretreatment of rat stomach fundus with tetrodotoxin (1 microM), atropine (1 microM), captopril (3 microM), prazosin (1 microM) or glibenclamide (1 microM) did not significantly modify the biphasic responses to BK (300 nM). The biphasic responses to DA-BK were antagonized selectively by the B1 receptor antagonist des-Arg9-[Leu 8]-BK (DAL BK) (1 microM). In contrast, the biphasic responses to BK were unaffected by DAL BK or by several selective peptide antagonists of B2 receptors including NPC 431 (Thi5,8, D-Phe7)-BK, NPC 349 (D-Arg Hyp3,Thi5,8,D-Phe7)-BK, NPC 567 (D-Arg-Hyp3,D Phe7)-BK and NPC 361 (D-Phe7)-BK (3 to 10 microM). These results are consistent with the view that the biphasic responses of the rat isolated stomach fundus to BK appear to be mediated by a novel BK receptor which is insensitive to blockade by B1 and B2 selective BK receptor antagonists. PMID- 1311793 TI - Effects of hirsutine, an antihypertensive indole alkaloid from Uncaria rhynchophylla, on intracellular calcium in rat thoracic aorta. AB - The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla (MIQ.) Jackson, on cytosolic Ca2+ level ([Ca2+]cyt) were studied by using fura-2-Ca2+ fluorescence in smooth muscle of the isolated rat aorta. Noradrenaline and high K+ solution produced a sustained increase in [Ca2+]cyt. Application of hirsutine after the increases in [Ca2+]cyt induced by noradrenaline and high K+ notably decreased [Ca2+]cyt, suggesting that hirsutine inhibits Ca2+ influx mainly through a voltage-dependent Ca2+ channel. Furthermore, the effect of hirsutine on intracellular Ca2+ store was studied by using contractile responses to caffeine under the Ca(2+)-free nutrient condition in the rat aorta. When hirsutine was added at 30 microM before caffeine treatment, the agent slightly but significantly reduced the caffeine-induced contraction. When added during Ca2+ loading, hirsutine definitely augmented the contractile response to caffeine. These results suggest that hirsutine inhibits Ca2+ release from the Ca2+ store and increases Ca2+ uptake into the Ca2+ store, leading to a reduction of intracellular Ca2+ level. It is concluded that hirsutine reduces intracellular Ca2+ level through its effect on the Ca2+ store as well as through its effect on the voltage-dependent Ca2+ channel. PMID- 1311794 TI - Effect of sex steroids on body temperature in postmenopausal women. Role of endogenous opioids. AB - The role of endogenous opioids on the thermoregulatory effect of sex steroids was investigated in six postmenopausal women before and during treatment with transdermal 17 B-estradiol (TTS 50; 50 mcg/day) with or without vaginal progesterone (P4; 100 mg twice daily). In all the different endocrine conditions, saline or the opioid antagonist naloxone (10 mg/hr. preceded by 10 mg iv bolus) were randomly infused for 4 hrs., on two consecutive days. Measurements of body temperature (BT) variations were performed by a thermistor probe placed in the rectum. BT did not significantly vary from baseline values during saline infusion, whereas it significantly decreased during the infusion of naloxone performed, either before treatment (p less than 0.01), during TTS 50 administration (p less than 0.01), or during TTS 50 + P4 (p less than 0.025). The naloxone induced decrease of BT was greater during TTS 50 administration than before treatment (p less than 0.025). The addition of P4 to TTS 50 administration increased baseline BT of 0.4 degrees C (p less than 0.01), and reduced the ability of naloxone to reduce BT (p less than 0.01 vs. TTS 50). The hyperthermic effect of P4 was not abolished by the infusion of naloxone. Our data show that in postmenopausal women the effect of endogenous opioid peptides on BT is enhanced by estradiol and reduced by progesterone. The hyperthermic effect of progesterone does not seem to be mediated by an increased endogenous opioid activity. PMID- 1311795 TI - An insulin-like growth factor II-producing histiocytoma associated with hypoglycemia: analysis of the peptide, its gene expression, and glucose transporter isoforms. AB - An insulin-like growth factor II (IGF-II)-producing histiocytoma was detected in a patient presenting with the classical findings of tumor-related hypoglycemia (low serum insulin and IGF-I concentrations, glucose intolerance, and only modestly increased serum IGF-II levels). Acid-gel filtration of serum extracts showed a single peak of IGF-II immunoreactivity that emerged at the same site as the 125I-labeled human IGF-II standard. High-performance liquid chromatography (HPLC) analysis of the tumor IGF-II demonstrated that it had an identical retention time to that of recombinant human IGF-II. The tumor IGF-II content was extremely high, messenger RNA (mRNA) for IGF-II showed a 100-fold increase in expression compared with normal human liver tissue. Of special interest, a newly identified exon (hE1) was shown to be predominantly expressed in the tumor by Northern blot analysis using leader exon-specific rat IGF-II complementary DNA (cDNA) probes. Although the significance of this finding remains uncertain, this is the first evidence of a new transcription unit in the human IGF-II gene. In addition, immunoblotting showed that the levels of the glucose transporters, GLUT1 and GLUT4, in the tumor were low and undetectable, respectively. This finding makes it unlikely that increased glucose consumption by the tumor accounted for the hypoglycemia in this patient. This case report provides an interesting insight into the pathophysiology of tumor-induced hypoglycemia and new evidence of the abnormal regulation of IGF-II gene expression in human tumors. PMID- 1311796 TI - Fructose 2,6-bisphosphate levels and modulation of glycolysis by histamine, cholecystokinin, and forskolin in isolated rabbit gastric glands. AB - In isolated rabbit gastric glands incubated in the presence of 1 mmol/L glucose, the content of fructose 2,6-bisphosphate (F-2,6-P2) was 5.7 +/- 0.5 pmol/mg dry weight. This value was progressively incremented by increasing glucose concentration in the incubation medium, and was almost doubled at 10 mmol/L glucose. Under these conditions, a close correlation could be established between the levels of F-2,6-P2 and the rate of L-lactate formation (r = .98; P less than .05). Both histamine (0.1 mmol/L) and cholecystokinin octapeptide (CCK-OCT; 0.1 mumol/L) increased L-lactate production, without significant changes in either F 2,6-P2 concentration or the amount of 6-phosphofructo-2-kinase in active form. In contrast, forskolin, which markedly increased the glandular content of cyclic adenosine monophosphate (cAMP), partially blocked glucose consumption and caused a significant reduction in both F-2,6-P2 levels and the proportion of 6 phosphofructo-2-kinase in active form. Furthermore, forskolin partially blocked the rate of glucose uptake by isolated gastric glands. Our results suggest a regulatory role of F-2,6-P2 in the control of the glycolytic flux in response to glucose, but not in its response to histamine or CCK-OCT. PMID- 1311797 TI - Drug treatment of cardiac arrest. PMID- 1311798 TI - Molecular cloning and expression of the gene encoding the kinetoplast-associated type II DNA topoisomerase of Crithidia fasciculata. AB - A type II DNA topoisomerase, topoIImt, was shown previously to be associated with the kinetoplast DNA of the trypanosomatid Crithidia fasciculata. The gene encoding this kinetoplast-associated topoisomerase has been cloned by immunological screening of a Crithidia genomic expression library with monoclonal antibodies raised against the purified enzyme. The gene CfaTOP2 is a single copy gene and is expressed as a 4.8-kb polyadenylated transcript. The nucleotide sequence of CfaTOP2 has been determined and encodes a predicted polypeptide of 1239 amino acids with a molecular mass of 138,445. The identification of the cloned gene is supported by immunoblot analysis of the beta-galactosidase-CfaTOP2 fusion protein expressed in Escherichia coli and by analysis of tryptic peptide sequences derived from purified topoIImt. CfaTOP2 shares significant homology with nuclear type II DNA topoisomerases of other eukaryotes suggesting that in Crithidia both nuclear and mitochondrial forms of topoisomerase II are encoded by the same gene. PMID- 1311799 TI - Identification of women at unsuspected risk of primary infection with herpes simplex virus type 2 during pregnancy. AB - BACKGROUND: Primary infections with herpes simplex virus type 2 (HSV-2) acquired by women during pregnancy account for about half of the morbidity and mortality from HSV-2 among neonates. The other half results from reactivation of old infections. Better methods are needed to identify which women are at risk for primary HSV-2 infection. METHODS: We prospectively studied HSV-2 infections among pregnant women who were patients in private obstetrical practices. Using an enzyme-linked immunosorbent assay that detects type-specific antibodies to HSV-2 glycoprotein G, we determined the prevalence at base line of HSV-2 infections among pregnant women and their husbands, the frequency of discordance for infection between partners, and the risk of seroconversion during pregnancy among the seronegative women whose husbands were seropositive. RESULTS: The seroprevalence of HSV-2 was 32 percent among the 277 women followed throughout their pregnancies and 25 percent among the 190 husbands studied. Two thirds of the HSV-2-seropositive women had no history of genital herpes. Of the 190 couples, 139 (73 percent) were serologically concordant for HSV-2 antibodies (57 percent being seronegative and 16 percent being seropositive), whereas 51 couples (27 percent) were discordant, despite having been sexually intimate for a mean of 6.1 years. Eighteen women who were seronegative for HSV-2 (9.5 percent) had seropositive partners, of whom 10 (56 percent) had no history of genital herpes. Thus, approximately 5 percent of these pregnant women had an unsuspected risk of contracting a primary HSV-2 infection. One of the 18 seronegative women with a seropositive husband seroconverted to HSV-2 during pregnancy; none of the other women seroconverted. CONCLUSIONS: In this study about 10 percent of pregnant women were at risk of contracting a primary HSV-2 infection from their HSV-2 seropositive husbands. In addition, about a third of these women were seropositive for HSV-2 and thus at risk for asymptomatic, reactivated infections. Serologic testing of couples can identify women who are at risk for primary or reactivated HSV-2 infections during pregnancy. PMID- 1311800 TI - Parainfluenza virus respiratory infection after bone marrow transplantation. AB - BACKGROUND: Pneumonia complicates about half of all bone marrow transplantations, and in about a third of the cases no specific cause is identified. Although parainfluenza virus is a common cause of respiratory infection in normal children, its role in transplant recipients is unknown. METHODS: We describe the incidence and clinical course of parainfluenza infection among the 1253 recipients of bone marrow transplants at our center from 1974 through 1990. We performed viral cultures on all such recipients who had manifestations of a viral infection or fever without apparent cause. RESULTS: Among the 1253 patients, we found 27 (2.2 percent) who had parainfluenza virus infection as demonstrated by culture (12 of 580 adults and 15 of 673 children). Eight of these patients had only upper respiratory tract involvement, all of whom had positive nasopharyngeal cultures. Of the remaining 19, 8 had symptoms of both upper and lower respiratory tract involvement, and 11 had only lower respiratory involvement, of whom only 6 had positive nasopharyngeal cultures. Four required bronchoalveolar lavage for diagnosis. A median of nine days elapsed from the onset of symptoms until the culture became positive, and overall only 33 of 118 cultures obtained were positive. Respiratory failure developed in 6 of the 19 patients with lower respiratory tract involvement, and all died. CONCLUSIONS: Parainfluenza virus is a cause of serious lower respiratory tract involvement in both adults and children who undergo bone marrow transplantation. Given the insensitivity of current culturing techniques, it may be underdiagnosed. PMID- 1311801 TI - Preventing neonatal herpes--current strategies. PMID- 1311802 TI - An ACTH4-9 analog enhances social attention in aging rats: a longitudinal study. AB - Effect of chronic treatment of the ACTH4-9 analog, Org2766, on social attention was studied longitudinally in aging rats. A 6-week treatment temporarily enhanced specific combinations of behaviors of two interacting animals. During a 6-month treatment social attention of treated animals remained at the same level, whereas control animals showed a gradual decrease. Two months after the treatment was ceased this effect on social attention was still present; moreover, the peptide treated animals performed better in a spatial water maze task three months after the last injection. In addition, the nerve conduction velocity of the major caudal nerves and the sciatic nerve were measured; aged, peptide-treated animals preserved their conduction velocity. The present study shows beneficial long lasting effects of the ACTH4-9 analog in aging rats on complex behavioral indices and on a physiological measure. PMID- 1311803 TI - The effect of aging on stress responsiveness and central corticosteroid receptors in the brown Norway rat. AB - The present study examined the stress responsiveness of the hypothalamic pituitary-adrenal axis in relation to the properties of corticosteroid receptors in the brain and pituitary of old (30 months) and young (3 months) male Brown Norway rats. Adrenocorticotropin hormone (ACTH) and corticosterone (B) were measured following exposure to novelty and to a conditioned emotional stimulus in blood samples sequentially obtained from chronically cannulated animals. Mineralocorticoid (MR) and glucocorticoid (GR) receptors were quantified by radioligand binding assay and in situ hybridization. The receptor binding constants were determined in tissue of rats that were adrenalectomized 24 hours previously, whereas gene expression was measured in the brain of intact animals. Aged Brown Norway rats showed a small but significant elevation in basal circulating ACTH level. The conditioned emotional stimulus, rather than the exposure to novelty, triggered a more than two-times higher ACTH response in the aged compared to the young rat. The termination of the stress-induced ACTH response seemed to proceed more efficiently in the aged rat. Basal and stress induced total plasma B level did not differ in the young and old rats. The latter showed a 65% lower binding capacity of corticosteroid-binding globulin (CBG). Interestingly, in the aged rat the stress-induced rise in free circulating plasma B level was not elevated, but only prolonged. The hippocampus of aged rats displayed a decrease of maximally 44% in the apparent Bmax of MR, but no change in GR number. The Bmax of GR showed a 40% reduction in the hypothalamus and a 50% reduction in the anterior pituitary. GR affinity was considerably increased in the anterior pituitary, but was unchanged in the hippocampus and hypothalamus. Old age affected MR and GR gene expression differentially. GR mRNA was significantly reduced in cell field CA3 (-42%), CA4 (-41%) and the dentate gyrus (-26%) of the dorsal hippocampus, but did not change either in hippocampal cell field CA1 or in the hypothalamic paraventricular nucleus (PVN) of the old rat. There was no significant difference in MR mRNA between young and aged rats in the different cell fields of the hippocampus. The aged rat, therefore, is characterized by site- and receptor-specific changes in binding constants as well as by changes in receptor transcription and translation. The data demonstrate that in the old Brown Norway rats, a conditioned emotional stimulus results in enhanced pituitary ACTH release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311804 TI - Identification of normal and pathological aging in prospectively studied nondemented elderly humans. AB - Results of a standardized histochemical and immunocytochemical analysis of the brains of 14 nondemented elderly humans for whom prospective neurological and neuropsychological data had been collected for 3 to 8 years before death suggested that nondemented elderly humans fall into two pathological subgroups that are not clinically distinguishable. One was associated with moderate to marked cerebral amyloid deposition ("pathological aging"), while the other had either minimal or no amyloid deposition ("normal aging"). Neocortical and hippocampal neurofibrillary degeneration was either completely absent or of very limited degree in both subgroups. Both subgroups had ubiquitin-immunoreactive dystrophic neurites in the cerebral cortex and granular degeneration of myelin in white matter. These ubiquitin-immunoreactive structures seem to be a universal and invariant manifestation of brain aging, but the same cannot be said for amyloid deposition and neurofibrillary degeneration. Pathological aging might be preclinical Alzheimer's disease, but it currently cannot be distinguished from normal aging by even sensitive neuropsychological measures. These findings provide strong support for the hypothesis that cerebral amyloid deposition is not necessarily associated with clinically apparent cognitive dysfunction and that additional factors, such as neuronal or synaptic loss or widespread cytoskeletal aberrations, are necessary for dementia in AD. PMID- 1311805 TI - Inositol 1,4,5-trisphosphate receptor in developing and senescent rat cerebellum. AB - Numerous process associated with intracellular calcium homeostasis have previously been found to vary with age. To determine whether the binding sites for the calcium-mobilizing second messenger, inositol 1,4,5-trisphosphate (InsP3), also displays such variation, [3H]InsP3 binding was investigated in cerebellar or cerebral cortical membranes prepared from rats at different ages from birth up to 24 months of age. In the cerebellum, the InsP3 receptor density was very low during the first week after birth, increased markedly between days 8 and 28 and then reached an apparent plateau between 28 to 56 days of age. The InsP3 receptor binding affinity was comparable at different developmental stages. No age-related differences were found in InsP3 receptor density or affinity in the cerebral cortex of 3-, 6-, 9-, 12-, and 24-month-old rats. In the cerebellum, InsP3 receptor density but not affinity was significantly reduced in 24-month-old compared only to 3-month-old animals. Our data suggest that the changes in InsP3 receptor binding during early development might reflect the growth and maturation of neurons containing these receptors (i.e., Purkinje cells). Furthermore, the age-dependent reduction in InsP3 receptor density, together with the recent report of senescent changes in protein kinase C activity, indicate that disruption of phosphoinositide second messenger system may be of importance to the impairment of neuronal responsiveness and behavioral deficits observed with aging. PMID- 1311806 TI - Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging. AB - Rats distributed over five different age groups, 3, 12, 18, 24 and 30 months of age, were screened for their spatial learning and memory ability in the Morris water maze, and the degree of place navigational impairments was correlated with morphological changes in the four major forebrain cholinergic cell groups (medial septum, MS; vertical limb of the diagonal band of Broca, VDB; nucleus basalis magnocellularis, NBM; and striatum) using choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr) histochemistry. Impaired place navigation developed progressively with age, such that 8% of the 12-month-old rats, 45% of the 18-month-old, 53% of the 24-month-old, and over 90% of the 30-month-old rats were behaviorally impaired. Significant reductions in the number of ChAT/NGFr positive cell bodies, amounting to between 19 and 45%, were observed in all four cell groups, and the remaining cells were reduced in size (6-24% reduction in cross-sectional area in the oldest age groups). Although the morphological changes were less severe and tended to develop later than the behavioral impairments, there was overall a significant correlation between water maze performance and ChAT/NGFr-positive cell counts, and to a lesser degree also cell size in all four cell groups. These changes were also highly correlated with age. The highest correlations were seen in MS, VDB and NBM, which are known to play a role in spatial memory performance in young rats. The results indicate that degenerative and/or atrophic changes in the forebrain cholinergic system and decline in spatial learning ability are parallel processes during aging. Although the magnitude of the morphological changes does not appear to be substantial enough, by itself, to explain the severe spatial learning impairments that develop in the oldest animals, the present data are consistent with the view that impaired function in the forebrain cholinergic system can contribute to age dependent cognitive decline in rodents. PMID- 1311807 TI - Pharmacological characterization of regulation of phosphoinositide metabolism by recombinant 5-HT2 receptors of the rat. AB - Transfection of 5-HT2 receptor cDNA in 293 cells induced the expression of a protein binding domain, exhibiting the classical 5-HT2 receptor transduction mechanism. Both [3H]DOB and [3H]spiperone high affinity binding sites were present in membranes of sense but not of antisense, 5-HT2 receptor cDNA transfected cells. Addition of 1 microM 5-HT induced a time-dependent increase of phosphoinositide (PI) metabolism in sense but not in antisense, 5-HT2 receptor cDNA transfected cells. Graded concentrations of 5-HT and of different serotonergic agonists showed different potencies (DOI greater than 5-HT greater than quipazine greater than DOM greater than alpha-methyl-5-HT greater than 8-OH DPAT greater than 2-methyl-5-HT greater than CGS-12066B) in stimulating turnover of PI in cells transfected with cDNA encoding for 5-HT2 receptors of the rat. The ability of different antagonists to inhibit 5-HT-stimulated turnover of PI bore a direct relationship with their potency to inhibit 5-HT2 receptor binding in cells transfected with 5-HT2 receptor cDNA (spiperone greater than ketanserin greater than ritanserin greater than mianserin greater than haloperidol). Preincubation of transfected 293 cells with pertussis toxin failed to modify either 5-HT- or DOI-induced activation of metabolism of PI. Pretreatment of transfected 293 cells with DOI (100 nM) for 2 hr or more, significantly reduced activation of turnover of PI elicited by graded doses of 5-HT. When the transfected 293 cells were exposed to DOI (100 nM) for 12 hr and the challenge was performed after a 2-hr wash-out period, the desensitization of the response to 5-HT was virtually abolished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311808 TI - The effect of systemic administration of baclofen on food intake in rats. AB - The effects of systemic administration of the GABAB agonist, baclofen was investigated on food intake in non-fasted rats. Baclofen (1.0, 2.0 and 4.0 mg/kg, s.c.) produced a dose-related increase in food intake in a free-feeding paradigm during the first 90 min after administration, with maximum increases occurring at a dose of 2 mg/kg (Experiment 1). Baclofen (0.5 and 1.0 mg/kg, s.c.) also increased food intake in the 40 min post-drug recording period in non-fasted rats, trained to make operant responses for food on a fixed-ratio schedule (Experiment 2). These results demonstrate that systemic administration of baclofen can stimulate ingestive behaviour in satiated rats and suggest a possible role for a GABAB receptor-mediated mechanism in the control of food intake. PMID- 1311809 TI - Electrophysiological effects of phencyclidine and the sigma agonist ditolylguanidine in the cerebellum of the rat. AB - The electrophysiological actions of phencyclidine (PCP) and the sigma agonist 1,3 di(2tolyl)guanidine (DTG) were examined in the cerebellum of urethane anesthetized rats. The object of the study was to determine if PCP and sigma agonists shared a common mechanism of action. The cerebellar Purkinje neuron was chosen because it has sigma receptors but not N-methyl-D-aspartate receptors, where PCP has additional effects. Both DTG and PCP decreased the spontaneous discharge rate of cerebellar Purkinje neurons after parenteral administration. When the drugs were applied locally to single Purkinje neurons, using pressure ejection through multibarrel micropipettes, both compounds decreased the spontaneous activity of the neurons with equal potency. Previous studies have shown that the actions of PCP in the cerebellum are dependent upon an interaction with noradrenergic terminals from the nucleus locus coeruleus. A similar finding was made in this study for DTG. Elimination of the noradrenergic input by lesion with the neurotoxin, 6-hydroxydopamine, diminished equally the effects of PCP and DTG. Treatment of the animals with haloperidol had similar effects. It is concluded that PCP and the sigma agonist DTG both act as indirect noradrenergic agonists in the cerebellum. PMID- 1311810 TI - Receptor-mediated volume regulation in astrocytes in primary culture. AB - Changes in astroglial volume were studied after incubating primary cultures from the cerebral cortex of newborn rats for 5 hr in taurine, glutamate or gamma aminobutyric acid (GABA), alone or together with monoamine receptor agonists. Control cell volume was 2.2 microliters/mg protein. In the presence of taurine or glutamate there was a small increase in cell volume, further augmented when the cells were incubated in isoproterenol plus taurine or phenylephrine, or isoproterenol plus glutamate. After incubation in 5-hydroxytryptamine (5-HT) plus taurine, on the other hand, the cell volume was not different from the control value. In the presence of GABA, alone or together with adrenoceptor agonists (alpha 1, alpha 2 or beta) or 5-HT, there were no significant changes in cell volume. The regulation of astroglial volume is complicated and affected by ion fluxes, free amino acids and metabolic events including changes in pH. The results are discussed in relation to late data on receptor regulation of active uptake of amino acids. Astroglial volume might be influenced by amino acid transport, partly under control of monoamine receptors. PMID- 1311811 TI - The effect of 3,3-dipyridylmethyl-1-phenyl-2-indolinone on the neuromuscular transmission in the rodent skeletal muscles. AB - The effects of a cognition enhancer, 3,3-dipyridylmethyl-1-phenyl-2-indolinone (DPMPI) (21.5-645 microM), on neuromuscular transmission were studied electrophysiologically on diaphragms of mouse and rat and the soleus muscle of rat. The drug DPMPI (21.5-645 microM) increased both direct and indirect twitch tension of mouse diaphragm. It also increased (a) the frequency of miniature endplate potentials and (b) the quantal content of endplate potential. However, DPMPI (64.5 microM) affected neither the amplitude of the directly elicited action potential of soleus muscle in the rat nor the magnitude of the resting membrane potential of mouse diaphragm, although DPMPI (215 microM) decreased the amplitude of the compound action potential of phrenic nerve. Based on these results, it is concluded that DPMPI had several effects on neuromuscular transmission, i.e. it (a) facilitated the transmitter releasing process of the motor nerve terminal, (b) decreased the conduction in the phrenic nerve and (c) increased the directly elicited twitch tension. PMID- 1311812 TI - Characteristics and function of Ca(2+)- and inositol 1,4,5-trisphosphate releasable stores of Ca2+ in neurons. AB - Molecular, biochemical and physiological evidence for the existence of releasable Ca2+ stores in neurons is strong. There are two separate molecules that function as release channels from those Ca2+ stores, the RyanR and InsP3R, and both have multiple regulatory sites for positive and negative control. Perhaps most intriguing is the biphasic, concentration-dependent action of cytosolic Ca2+ on both channels, first to stimulate release then, at higher concentration, to depress release. Whether the InsP3R and RyanR channels regulate Ca2+ release from different or identical functional compartments will need to be defined for each neuron type and perhaps even for each intracellular region within neurons since the evidence for functional separation of stores is mixed. The identification of Ca2+ storage and releasing capacity throughout all subcellular regions of neurons and the increasing evidence for a role for Ca2+ stores in neuronal plasticity suggests that the further characterization of the functional properties of Ca2+ stores will be an increasingly important and expanding area of interest in neurobiology. PMID- 1311813 TI - Isolation of glutamate-binding proteins from rat and bovine brain synaptic membranes and immunochemical and immunocytochemical characterization. AB - We previously isolated two glutamate-binding proteins from rat brain synaptic membranes of 71,000 and 63,000 mol. wt [Chen et al. (1988) J. biol. Chem. 263, 417-426]. In the present study, the 71,000 and 63,000 mol. wt glutamate-binding proteins were purified from rat and bovine brain synaptic membranes by affinity chromatographic separation on an L-glutamate-derived Trisacryl matrix. The major protein component in the purified fractions was a 71,000 mol. wt protein as judged by sodium dodecyl sulfate gel electrophoresis. This fraction represented enrichment of bovine brain glutamate-binding proteins by a factor of 7000-8000 when compared with brain homogenates. The ligand binding characteristics of the proteins purified by this new procedure are very similar to those of the proteins purified by the procedures we described in previous studies. Polyclonal antibodies were raised in mice against the purified, native rat and bovine brain glutamate-binding proteins. These two sets of antibodies interacted specifically with the glutamate-binding proteins but not with any glutamate-metabolizing enzymes. Both sets of antibodies labeled a 71,000 mol. wt protein in Western blots of synaptic membranes obtained from either rat or bovine brain, an indication of homology between these proteins. Both sets of antibodies produced immunoprecipitation of approximately 70-75% of all glutamate-binding proteins from solubilized synaptic membrane proteins. These observations are an indication that the glutamate-binding proteins described above are the most common glutamate binding entities in both bovine and rat brain synaptic membranes and that they can be easily purified in a one-step chromatographic procedure. PMID- 1311814 TI - Contrasting patterns in the localization of glutamic acid decarboxylase and Ca2+/calmodulin protein kinase gene expression in the rat central nervous system. AB - The expression of the genes encoding the alpha subunit of type II calcium calmodulin-dependent protein kinase (CaM II kinase alpha) and the 67,000 mol. wt form of glutamic acid decarboxylase was examined throughout the rat central nervous system. In situ hybridization histochemistry, using cRNA probes, revealed a dense population of CaM II kinase alpha-expressing cells throughout the telencephalon and diencephalon. CaM II kinase alpha mRNA was also expressed in the midbrain, cerebellum and medulla oblongata, but at greatly reduced levels. No CaM II kinase alpha gene expression was detected in nuclei producing monoamines or acetylcholine. By contrast, the glutamic acid decarboxylase gene was moderately to highly expressed throughout the central nervous system. In several regions there was a complementarity in the distributions of cells expressing the glutamic acid decarboxylase or CaM II kinase alpha genes. Cells in certain nuclei such as the thalamic reticular nucleus or globus pallidus showed glutamic acid decarboxylase gene expression only; others such as the majority of the dorsal thalamic nuclei showed CaM II kinase alpha gene expression only. Several regions contained both glutamic acid decarboxylase and CaM II kinase alpha expressing cells. However, simultaneous immunostaining for both proteins revealed only two regions where CaM II kinase alpha and glutamic acid decarboxylase immunoreactivity were colocalized: the cerebellar Purkinje cells and the commissural nucleus of the stria terminalis. The results imply that CaM II kinase alpha is primarily expressed in non-GABAergic neurons. In several regions CaM II kinase alpha mRNA is concentrated in nuclei known to contain populations of neurons that use excitatory amino acid transmitters. PMID- 1311815 TI - Dendritic localization of type II calcium calmodulin-dependent protein kinase mRNA in normal and reinnervated rat hippocampus. AB - In situ hybridization histochemistry has revealed a diffuse distribution of the alpha subunit of type II calcium calmodulin-dependent protein kinase (CaM II kinase alpha) mRNA in the neuropil of regions containing CaM II kinase alpha expressing cells and has led some to propose that it may be expressed in dendrites. In order to determine if CaM II kinase alpha mRNA is expressed in dendrites and if the gene encoding CaM II kinase alpha is regulated in response to synaptic reinnervation, we examined its expression in the hippocampus of normal rats, of rats that had received a unilateral injection of kainic acid and of rats with a unilateral entorhinal cortex lesion. The relatively specific elimination of the CA3 pyramidal cells by kainate lesions precisely correlated with the loss of CaM II kinase alpha cRNA hybridization in the stratum radiatum as well as the stratum pyramidale. Following entorhinal cortex lesions, during the period of new synapse formation in the dentate gyrus, there was no detectable change in the level of CaM II kinase alpha gene expression. These data suggest that CaM II kinase alpha mRNA is expressed in the dendrites of hippocampal pyramidal cells and, therefore, is likely to be expressed in dendrites in other regions of the central nervous system exhibiting CaM II kinase alpha cRNA labeling in the neuropil. However, changes in expression were not found to accompany new synapse formation. PMID- 1311816 TI - Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II. AB - Insulin-like growth factors have a number of potent trophic effects on cultured neural tissue and most if not all of these effects appear to be mediated by the type-I insulin-like growth factor receptor. In order to establish the identity of cell types expressing this receptor in the rat central nervous system during development and maturity, we have used in situ hybridization to map sites of type I insulin-like growth factor receptor mRNA synthesis in the developing and adult rat brain. In order to identify possible local sources of peptide ligands for this receptor, we have also mapped the sites of insulin-like growth factors I and II mRNA synthesis in parallel brain sections. From early development onward, there is a uniform and stable pattern of type-I insulin-like growth factor receptor gene expression in all neuroepithelial cell lineages, in which regional variations reflect primarily differences in cell density. In addition to this generalized pattern, during late postnatal development, high levels of type-I insulin-like growth factor receptor gene expression are found in specific sets of sensory and cerebellar projection neurons in conjunction with abundant insulin like growth factor-I gene expression in these same neurons. While insulin-like growth factor-I expression is confined to the principal neurons in each system, receptor mRNA is also found in local interneurons. In the cerebral cortex and hippocampal formation, type-I insulin-like growth factor receptor mRNA and insulin-like growth factor-I are concentrated in different cell populations: receptor mRNA is abundant in pyramidal cells in Ammon's horn, in granule cells in the dentate gyrus, and in pyramidal cells in lamina VI of the cerebral cortex. Insulin-like growth factor-I mRNA is found in isolated medium- to large-sized cells which are rather irregularly distributed throughout the hippocampus and isocortex. In the hypothalamus, receptor mRNA is concentrated in the suprachiasmatic nucleus but is in low abundance elsewhere, including the median eminence, while insulin-like growth factor-I mRNA is not detected in this region at all. Type-I insulin-like growth factor receptor and insulin-like growth factor II mRNAs are both abundant in choroid plexus, meninges and vascular sheaths from early development to maturity, but insulin-like growth factor-II mRNA is not detected in cells of neuroepithelial origin at any stage of development. This study provides evidence for two fundamentally different patterns of gene expression for the brain type-I insulin-like growth factor receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1311817 TI - Primary receptor for inhibitory transmitters in lamprey spinal cord neurons. AB - The action of glycine and GABA on isolated lamprey spinal cord neurons was investigated by means of intracellular perfusion and concentration clamp techniques. These amino acids activated desensitizing chloride ionic conductances. The concentrations of agonists evoking half-maximum effects (ED50) were equal to 16 microM and 1.5 mM for glycine- and GABA-activated currents, respectively. Increase in the transmitter concentration led to a decrease in the time constant of desensitization. Current-voltage relationships of glycine- and GABA-activated currents were strongly dose-dependent. At low agonist concentrations the time constant of activation decreased with membrane hyperpolarization. Glycine- and GABA-activated currents exhibited complete cross desensitization. The specific glycine antagonist, strychnine, suppressed both glycine- and GABA-activated currents to the same degree. Selective antagonists of GABA receptors, bicuculline and picrotoxin, produced equal blocking effects on glycine- as well as GABA-evoked responses. In the cells studied, taurine activated desensitizing ionic conductance. Responses evoked by taurine and glycine applications demonstrated complete cross-desensitization. Taurine activated currents were sensitive to strychnine, bicuculline and picrotoxin. These results suggest the existence of one receptor-channel complex for the main inhibitory transmitters in lamprey spinal cord neurons. 3,4-Dioxy-L-beta phenylalanine evoked desensitizing strychnine-sensitive ionic responses which exhibited cross-desensitization with glycine-activated currents. PMID- 1311818 TI - Postischemic binding of [3H]phorbol 12,13-dibutyrate and [3H]inositol 1,4,5 trisphosphate in the gerbil brain: an autoradiographic study. AB - Postischemic alteration of second messenger systems was investigated in the Mongolian gerbil, utilizing [3H]phorbol 12,13-dibutyrate and [3H]inositol 1,4,5 trisphosphate receptor autoradiography. Transient ischemia was induced for 10 min, and animals were allowed to survive for various recirculation periods of up to one month. [3H]Phorbol 12,13-dibutyrate binding in selectively vulnerable areas showed no significant change 1-24 h after ischemia except for a transient decline in a few regions. Thereafter, the binding in most of the selectively vulnerable areas showed significant alteration 48 h or seven days after ischemia. Interestingly, dentate molecular layer which was resistant to ischemia showed a significant elevation in the number of [3H]phorbol 12,13-dibutyrate binding sites. One month after ischemia, [3H]phorbol 12,13-dibutyrate binding showed significant reduction only in the striatum and the hippocampal CA1 sector where severe neuronal damage was seen morphologically. A significant elevation in the number of [3H]phorbol 12,13-dibutyrate binding sites was still seen in the dentate molecular layer one month after ischemia. In contrast, [3H]inositol 1,4,5 trisphosphate binding showed significant reduction in the selectively vulnerable regions 1-24 h after ischemia. Thereafter, [3H]inositol 1,4,5-trisphosphate binding in most of the selectively vulnerable areas markedly decreased up to one month after ischemia. In the dentate molecular layer, [3H]inositol 1,4,5 trisphosphate binding also showed significant reduction during recirculation except for a slight recovery 48 h and seven days after ischemia. One month after ischemia, the binding in all regions showed significant reduction. These results suggest that postischemic alteration of two second messenger (protein kinase C and inositol 1,4,5-trisphosphate) binding sites was produced with different processes in selectively vulnerable areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311819 TI - Adenosine-dependent enhancement by methylxanthines of excitatory synaptic transmission in hippocampus of rats. AB - Whole-cell patch-clamp was used to investigate synaptic transmission in hippocampal slices. Excitatory post-synaptic currents (EPSCs) were facilitated by low (less than or equal to 1 microM) adenosine (Ado) concentrations, while high concentrations had well-known inhibitory effects on the EPSC. When added on the background of preapplied Ado, methylxanthines caused a large potentiation of EPSCs. At saturation, the enhanced EPSC could exceed the control almost by an order of magnitude. Pertussis toxin strongly impaired the ability of Ado to block EPSCs but did not augment the facilitatory effect. The two components of the EPSC mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors were facilitated simultaneously and in equal proportions. PMID- 1311820 TI - HS-142-1, a novel non-peptide ANP antagonist, blocks the cyclic GMP production elicited by natriuretic peptides in PC12 and NG108-15 cells. AB - HS-142-1 is a novel non-peptide antagonist for atrial natriuretic peptide (ANP) receptor. The effect of HS-142-1 on the cyclic GMP production elicited by natriuretic peptides in neuronal cell lines, PC12 and NG108-15 was examined. Natriuretic peptides such as ANP, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) enhanced cyclic GMP production in a dose-dependent manner. HS-142-1 inhibited cyclic GMP accumulation elicited by natriuretic peptides in a dose-dependent fashion in both cells. The results suggest that HS 142-1 will be an important tool for identification and understanding of the mechanisms by which natriuretic peptides act in nervous systems. PMID- 1311821 TI - Chronic elevation of cAMP levels induces changes in the adenylate cyclase system, opiate receptor sensitivity and levels of Gs-mRNA in cultured neurons. AB - Neurons in primary culture were treated (5 days) with the adenylate cyclase stimulator 10(-5) M forskolin. The basal adenylate cyclase was decreased by 57%. The acute stimulatory effect of forskolin was down-regulated by 48%. The inhibitory effects of the 3 opiate receptor agonists (mu, delta and kappa) were partly abolished. The abundance of mRNA encoding the stimulatory G-protein (Gs) was decreased prominently. The data indicate that the cAMP system in neuronal cells in primary culture is under dynamic regulation, possibly including altered Gs-protein gene expression. Furthermore, long-term forskolin treatment might induce increased proliferation in susceptible neural blast cells. PMID- 1311822 TI - Fast and slow twitch skeletal muscle fibres differ in their distribution of Na channels near the endplate. AB - Sodium channel distributions were measured in fast and slow twitch rodent skeletal muscle fibres using the loose patch voltage clamp technique. Large differences were found between these fibre types with respect to Na channel density in the perijunctional region. Fast twitch fibres exhibited a large increase in Na channel density near the endplate, while slow twitch fibres did not. PMID- 1311823 TI - Alteration of pituitary-adrenal responses to adrenalectomy by the immunological targeting of CRF neurons. AB - We previously demonstrated that cellular toxins added to a cytotoxic IgG2a monoclonal antibody to corticotropin releasing factor (CRF-MAb) may specifically penetrate some hypothalamic CRF neurons, after central injection near the paraventricular nuclei. We attempt here to evaluate the consequential effects on the CRF neurons functioning. Such a toxic mix, 4 weeks after its central injection, caused a marked reduction (66%) of the chronic adrenocorticotropic hormone (ACTH) release in response to a bilateral adrenalectomy (7th day). This change was accompanied by a reduction in the CRF concentration (43%) measured in the median eminence. We concluded that specific internalization of toxins, by the way of CRF-MAb, leads to a long-term dysregulation of the CRF synthesis and/or neuronal transport. PMID- 1311824 TI - Studies on the spinal interaction of morphine and the NMDA antagonist MK-801 on the hyperesthesia observed in a rat model of sciatic mononeuropathy. AB - This study evaluated the effects of intrathecally coadministered morphine and the N-methyl-D-aspartate (NMDA) antagonist (+)5-methyl-10,11-dihydro-5H- dibenzocyclohepten-5,10-imine maleate (MK-801) on the thermally evoked hindpaw withdrawal latency (PWL) in rats with one paw (ipsilteral) rendered hyperesthetic by the unilateral application of loose ligatures to the sciatic nerve (delta PWL (+/- S.D.) = PWLhyperesthetic paw - PWLnormal paw = -3.1 +/- 1.2 s). Intrathecal morphine produced a dose-dependent (0.1-10 micrograms; P less than 0.0001) elevation in the thermal response latency of both the contralateral (normal) and ipsilateral (hyperesthetic) paw. delta PWL did not vary with morphine, indicating that the dose-response curves were parallel but shifted to the right for the hyperesthetic paw. For the normal paw, MK-801 (10 micrograms) was without effect upon the response latency; whereas, the response latency of the hyperesthetic paw was elevated to the same as the normal paw, i.e. the hyperesthesia was selectively abolished (delta PWL (+/- S.D.) = -0.067 +/- 2.73). Co-administration of MK-801 with morphine did not alter the effects of morphine in the normal paw, but reduced the delta PWL for each dose of morphine. These results suggest that NMDA antagonism (1) does not alter the thermal sensitivity in the normal paw, (2) selectively abolishes the hypersensitivity of the hypersthetic paw and (3) has a simple additive interaction with the antinociceptive effects of morphine in the hyperesthetic paw. PMID- 1311825 TI - Home care for AIDS patients. AB - Home care is influencing the provision of care for AIDS patients by providing a cost-effective, efficacious alternative site for the delivery of care. As the number of AIDS patients and the associated health care costs increase, home care for AIDS patients will continue to expand. PMID- 1311826 TI - Intravenous immunoglobulin in chronic relapsing polyneuropathy. PMID- 1311827 TI - AIDS protection can only be assured by education. PMID- 1311828 TI - Telephone follow-up programs as creative nursing interventions. AB - Perinatal nurses responded to their own concerns and to those expressed by their patients with the development of a follow-up program. This program proposed a way to extend comprehensive care and teaching after hospital discharge. A valuable approach in postpartum, this program also lends itself to areas such as the NICU and PICU. PMID- 1311829 TI - Hemodynamic effects of heat-killed group B beta-hemolytic streptococcus in newborn lambs: role of leukotriene D4. AB - Group B beta-hemolytic streptococcus (GBS) infection is an important cause of neonatal pneumonia and sepsis. GBS infection is frequently associated with persistent pulmonary hypertension of the newborn. To better understand the early pulmonary hypertension phase of GBS-induced acute lung injury in a conscious animal, we characterized the pulmonary and systemic hemodynamic response of spontaneously breathing, chronically instrumented newborn lambs to injections of heat-killed type Ib GBS, 0.1-9.0 x 10(9) colony forming units. Heat-killed GBS caused marked dose-dependent increases in mean pulmonary arterial pressure and calculated pulmonary vascular resistance, 190 and 370% at the maximum dose, respectively. Similarly, GBS caused dose-dependent increases in mean systemic arterial pressure and systemic vascular resistance (28.5 and 108% at the maximum dose, respectively) and a decrease in cardiac output (33.5%). Arterial oxygen tension worsened at the higher doses. GBS-induced pulmonary hypertension was decreased by two structurally unrelated, putative leukotriene D4 receptor antagonists. Pretreatment with LY171883 blocked GBS-induced pulmonary hypertension by 95%, and WY48,252 attenuated this effect by 27%. Both drugs completely blocked the hemodynamic effects of exogenous leukotriene D4. For comparison, several lambs received bolus injections of live GBS, either alone or after pretreatment with LY171883. The hemodynamic response to live GBS and attenuation of that response by LY171883 were similar to those caused by similar doses of heat-killed GBS. Thus, bolus injections of heat-killed GBS provide a reproducible model of pulmonary hypertension in conscious newborn lambs. In addition, the sulfidopeptide leukotrienes appear to be important mediators of GBS induced pulmonary hypertension in newborn lambs. PMID- 1311830 TI - Retroposons do jump: a B2 element recently integrated in an 18S rDNA gene. AB - Several cDNA clones were isolated from cDNA libraries constructed with mRNA longer than 28S RNA from the murine cell line PYS-2/12. The plasmids have inserts containing 1-1.2 kb of the ribosomal 5' external transcribed spacer followed by nearly 700 nt of sequence for 18S rRNA and ending with a B2 element (retroposon). The cloned sequence differed in a few positions from published ribosomal sequences. The 3' adjacent genomic sequence was obtained by polymerase chain reaction (PCR) and showed that the B2 element has a poly(A) tail of about 50 nt and is surrounded by perfect direct repeats of 15 nt. Analysis of genomic DNA from several murine cell lines revealed that PYS cells contain at least one copy of 18S RNA with the B2 element which is not present in the genome of other murine cell lines derived from the same teratocarcinoma. Similarly, rRNA transcripts containing the B2 element were only detected in PYS cells. According to the publication dates of the different cell lines, the B2 element must have been integrated into an rRNA transcription unit during the years 1970 through 1974 thus proving that retroposons (SINEs) can still be inserted into the genome in our times. PMID- 1311831 TI - Use of alternative polyadenylation sites for tissue-specific transcription of two angiotensin-converting enzyme mRNAs. AB - The pulmonary isozyme of rabbit angiotensin-converting enzyme (ACE) is encoded by an mRNA of about 5 kb. cDNA clones corresponding to different parts of this mRNA have been isolated and the complete nucleotide sequences of both the coding and non-coding regions of the mRNA have been determined. The encoded protein has 1309 residues with a 33 amino acids-long signal peptide at the amino terminus and a potential membrane-anchoring domain near the carboxyl terminus. There is a strong sequence homology between two regions of the rabbit cDNA and between the rabbit, human, and mouse cDNAs. Comparison of the nucleotide sequences of the 3' untranslated regions of rabbit pulmonary and testicular ACE cDNAs revealed that the testicular cDNA is nested within the pulmonary cDNA at the 3' end. A rabbit genomic clone encompassing this region was isolated and partially sequenced. It was shown that the gene contains two potential polyadenylation sites 628 bp apart within one exon. Northern analyses with an appropriate oligonucleotide probe confirmed that the proximal polyadenylation site is used exclusively for terminating the testicular mRNA whereas the distal one is used exclusively for the pulmonary mRNA. These results demonstrated that the transcription of the two mRNAs encoding the two ACE isozymes not only initiates at two alternative tissue specific sites which are 5.7 kb apart but the mRNAs also get polyadenylated at two alternative sites which are 628 bp apart. PMID- 1311832 TI - Evidence that nucleosomes on the mouse mammary tumor virus promoter adopt specific translational positions. AB - We have previously demonstrated that an array of six nucleosomes are phased on the mouse mammary tumor virus (MMTV) long terminal repeat (1,2). In this study, we devised a new assay to measure the translational positions of specific nucleosomes on the MMTV promoter. Nucleosome core particles were purified and shown to contain A and B nucleosomal DNA by Taq polymerase primer extension with nucleosome-specific primers. The 5' and 3' boundaries of A and B nucleosomes were measured by extending to the end of the core DNA with internal primers. This approach yielded results consistent with major translational positions of -23 to +123 and -221 to -75 for A and B nucleosomes, respectively. The micrococcal nuclease cleavage patterns of A and B nucleosome regions in isolated nuclei are conserved at base-pair resolution in multiple murine cell lines containing either stable MMTV-reporter chimeras or endogenous proviruses. As the refined nucleosome positions place important transcription factor binding sites at the 3' edge of the B nucleosome and in the nucleosome A/B linker, we propose that linker histone depletion and chromatin unfolding may be required to expose these cis-elements during steroid hormone-induced transcription initiation. PMID- 1311833 TI - Immunoprecipitation of SV40 replicating minichromosomes complexed with bacteriophage T4 gene 32 protein. AB - Simian Virus 40 (SV40) DNA replication is a useful model to study eukaryotic cell DNA replication because it encodes only one replication protein and its genome has a nucleoprotein structure ('minichromosome') indistinguishable from cellular chromatin. Late after infection SV40 replicating DNA molecules represent about 5% of total viral minichromosomes. Since gene 32 protein (P32) from bacteriophage T4 interacts with single-stranded DNA and SV40 replication complexes are expected to contain single-stranded regions at the replication forks, we asked whether P32 might be used to isolate replicating SV40 minichromosomes. When nuclear extracts from SV40 infected cells were treated sequentially with P32 and anti-P32 antibodies, pulse-labeled minichromosomes were selectively immunoprecipitated. Agarose gel electrophoresis analysis confirmed that immunoprecipitated material corresponded to SV40 replicative intermediates. Protein analysis of the pelleted material revealed several proteins of viral and cellular origin. Among them, T antigen and histones were found to be complexed with at least other three proteins from cellular origin, to the replicative complexes. Additionally, anti P32 antibodies were able to detect three cellular proteins of approximately 70, 32 and 13 kDa in western blots. These proteins could correspond to those found as part of an eukaryotic multisubunit single-stranded DNA binding protein. The use of P32 and anti-P32 antibodies thus allows the separation of replicating from mature SV40 minichromosomes and can constitute a novel method to enrich and to study replicative active chromatin. PMID- 1311834 TI - The use of RNase H and poly(A) junction oligonucleotides in the analysis of in vitro polyadenylation reaction products. PMID- 1311835 TI - A pitfall of using a second plasmid to determine transfection efficiency. PMID- 1311836 TI - Dinucleotide repeat polymorphism at the IGF2R locus. PMID- 1311837 TI - Dinucleotide repeat polymorphism at the D5S98 locus. PMID- 1311838 TI - Detection of HPV 16/18 DNA in cervical adenocarcinoma using polymerase chain reaction (PCR) methodology. AB - Twenty-two tissue samples of primary adenocarcinoma (adenoCA) of the uterine cervix were evaluated for the presence of HPV 16/18 DNA using the polymerase chain reaction (PCR). PCR was used to specifically amplify the E6-E7 gene region of HPV 16/18 DNA. The amplification products were analyzed using gel electrophoresis and Southern dot blotting with 32p labeled type-specific oligonucleotide probes. HPV 18 DNA was identified in 13/22 (59%) and HPV 16 DNA was identified in 5/22 (23%) of the tumors. There were no tumors with mixed infections. In three patients, two different specimens were evaluated, and there was concordance of HPV typing. The presence of squamous carcinoma in situ, koilocytosis and younger patient age were associated with an increased incidence of HPV 16/18 DNA detection. HPV 16/18 DNA was not detected in six metastatic adenoCA to cervix (four endometrial, two ovarian). We conclude that HPV 16/18 DNA is present in a significant proportion of primary adenoCA of the cervix, and we have identified some clinicopathologic associations. The detection of HPV DNA may be useful in distinguishing primary from metastatic adenoCA of the cervix. PMID- 1311839 TI - Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis. AB - The relationship of various verruciform squamous cell proliferations of the penis such as verrucous carcinoma, with or without anaplasia and giant condyloma, is uncertain. We conducted clinicopathologic, flow cytometric, and HPV typing studies on 15 cases of penile verrucous carcinoma to investigate its place in the spectrum of genital squamous proliferations. The results show a high degree of morphologic uniformity with respect to Ackerman's original diagnostic criteria, as well as to several other histopathologic features evaluated. The latter include polygonal squamous cells with glassy cytoplasm, centrally located vesicular nuclei, intercellular edema, well-formed cellular bridges, and absence or paucity of koilocytes, true fibrovascular cores, and keratohyalin granules. Intraepithelial abscesses and crust-formation were present in many cases. Four cases contained microscopic foci of cellular anaplasia. These hybrid verrucous squamous carcinomas presented and behaved similarly to the pure verrucous carcinomas. Tumor recurrence was correlated with extent of initial surgical management. DNA ploidy analysis by flow cytometry performed on eight pure and two hybrid tumors showed uniform diploid populations with similar G1/G2 fractions in both groups. Eight pure and two hybrid tumors evaluated for HPV by isotopic in situ hybridization were uniformly negative for HPV types 6, 11, 16, 18, and 31. The results show that penile verrucous carcinoma demonstrates characteristic and uniform morphologic features and does not contain the HPV types typically associated with condyloma acuminatum, giant condyloma of Buschke-Lowenstein, and condylomatous carcinoma. PMID- 1311840 TI - Epstein-Barr virus in Hodgkin's disease from patients with human immunodeficiency virus infection. AB - The polymerase chain reaction (PCR) technique was used to detect the presence of Epstein-Barr virus (EBV) DNA sequences in Hodgkin's disease specimens from 10 patients who were also positive for the human immunodeficiency virus (HIV). Eight of 10 specimens were positive for EBV, compared to 23 of 57 Hodgkin's disease specimens from patients without HIV infection, suggesting a closer association between Epstein-Barr virus infection and Hodgkin's disease in patients with HIV infection than in the general population. PMID- 1311841 TI - Artificial mobile DNA element constructed from the EcoRI endonuclease gene. AB - There exist several examples of mobile group I introns. These introns appear to use a straightforward mechanism to achieve highly site-specific and efficient insertion into homologous intronless genes. Because the only intron-specific function required by the prevailing model for the mechanism of intron mobility is the introduction of a site-specific double-stranded break in the intronless recipient DNA molecule, we reasoned that it should in principle be possible to construct artificially mobile DNA sequences. We have constructed an artificial mobile element from the gene for the restriction enzyme EcoRI that is capable of site-specific insertion at rates near those of authentic mobile introns. The generality of the mobility mechanism may enable high-efficiency targeted gene replacements or disruptions in a variety of organisms. PMID- 1311842 TI - Global control in Pseudomonas fluorescens mediating antibiotic synthesis and suppression of black root rot of tobacco. AB - Pseudomonas fluorescens CHA0 colonizes plant roots, produces several secondary metabolites in stationary growth phase, and suppresses a number of plant diseases, including Thielaviopsis basicola-induced black root rot of tobacco. We discovered that mutations in a P. fluorescens gene named gacA (for global antibiotic and cyanide control) pleiotropically block the production of the secondary metabolites 2,4-diacetylphloroglucinol (Phl), HCN, and pyoluteorin. The gacA mutants of strain CHA0 have a drastically reduced ability to suppress black root rot under gnotobiotic conditions, supporting the previous observations that the antibiotic Phl and HCN individually contribute to the suppression of black root rot. The gacA gene is directly followed by a uvrC gene. Double gacA-uvrC mutations render P. fluorescens sensitive to UV irradiation. The gacA-uvrC cluster is homologous to the orf-2 (= uvrY)-uvrC operon of Escherichia coli. The gacA gene specifies a trans-active 24-kDa protein. Sequence data indicate that the GacA protein is a response regulator in the FixJ/DegU family of two-component regulatory systems. Expression of the gacA gene itself was increased in stationary phase. We propose that GacA, perhaps activated by conditions of restricted growth, functions as a global regulator of secondary metabolism in P. fluorescens. PMID- 1311843 TI - Synergistic and coordinate expression of the genes encoding ribonucleotide reductase subunits in Swiss 3T3 cells: effect of multiple signal-transduction pathways. AB - Ribonucleoside-diphosphate reductase (ribonucleotide reductase, EC 1.17.4.1) is the enzyme responsible for the in vivo production of deoxyribonucleotides for DNA synthesis and is essential for cell proliferation. We examined the signal transduction pathways leading to expression of the M1 and M2 subunits of this enzyme in Swiss 3T3 mouse fibroblasts by Northern blot analysis. Stimulation of quiescent cells resulted in coordinate expression of both subunits, beginning at 8 hr after serum addition, in late G1 phase, and peaking at 18-24 hr. Serum increased M2 message to 30 to 50 times that of quiescent cells, in contrast with M1 message, which was increased 10 times. Agents that elevated cAMP, including forskolin, and the cAMP analogue 8-bromo-cAMP modestly stimulated gene expression. Each of these agents was synergistic with insulin, and these combinations induced expression equivalent to that induced by serum stimulation. Likewise, agents that activate protein kinase C such as phorbol 12,13-dibutyrate, bombesin, and vasopressin were also synergistic with insulin with respect to ribonucleotide reductase gene expression, as was epidermal growth factor, which stimulates receptor tyrosine kinase activity. The time course for induction of mRNA expression by each of these agents alone or in combination was identical to that for induction stimulated by serum. Finally, the synergistic effects apparent in Northern analysis of ribonucleotide reductase gene expression were mirrored in parallel determinations of DNA synthesis. Thus, the combinatorial nature of signal transduction pathways resulting in proliferation of Swiss 3T3 cells is expressed at the level of ribonucleotide reductase gene expression. PMID- 1311844 TI - Localizing genes on the map of the genome of Haloferax volcanii, one of the Archaea. AB - We have assigned genetic markers to locations on the physical map of the genome of the archaeon Haloferax volcanii, using both a physical method (hybridization) and a more specific genetic technique (transformation with cosmids). Hybridizations were against restriction digests of each of 151 cosmids making up a minimally overlapping set and covering 96% of the genome. Results with a cloned insertion sequence and a tRNA probe indicated that transposable elements are concentrated on two of the four plasmids of this species, whereas regions complementary to tRNA are largely chromosomal. For a genetic analysis of genes involved in the biosynthesis of amino acids, purines, and pyrimidines, we used cosmid transformation to assign 139 of 243 ethyl methanesulfonate-induced auxotrophic mutations, generated and characterized for this study, to single cosmids or pairs of cosmids from the minimal set. Mutations affecting the biosynthesis of uracil, adenine, guanine, and 14 amino acids have been mapped in this way. All mutations mapped to the 2920-kilobase-pair chromosome of Hf. volcanii and seemed uniformly distributed around this circular replicon. In some cases, many mutations affecting a single pathway map to the same or overlapping cosmids, as would be expected were genes for the pathway linked. For other biosynthetic pathways, several unlinked genetic loci can be identified. PMID- 1311845 TI - Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. AB - We describe the molecular cloning of a receptor tyrosine kinase from a cell line (LK63) derived from a case of human pre-B-cell leukemia. We have previously shown that a monoclonal antibody (IIIA4) raised against LK63 recognized a glycosylated, cell-surface 135-kDa molecule (HEK), which displayed tyrosine kinase activity in vitro. The HEK protein was purified by using a IIIA4 antibody column and both N terminal and internal amino acid sequences were obtained. A 51-mer degenerate oligonucleotide based on the internal amino acid sequence was used to screen an LK63-derived lambda gt10 cDNA library under low-stringency hybridization conditions. One clone of 2.5 kilobases (kb) was isolated and characterized and used to rescreen the library under more-stringent hybridization conditions. A 4.5 kb clone containing the entire HEK coding region was isolated and its complete DNA sequence was determined. The 4.5-kb insert was subcloned into the expression vector CDM8 and transfected into COS cells. COS cells transfected with the sense HEK/CDM8 construct stained specifically with the IIIA4 antibody, thereby confirming that the antigen recognized by the IIIA4 antibody and the expressed protein product of the HEK cDNA clone were identical. DNA sequence analysis revealed that HEK is a newly discovered member of the EPH/ELK family of receptor tyrosine kinases. Northern blot analysis of a number of cell lines demonstrated the expression of 5.5- to 6.0-kb HEK transcripts in LK63 and the T-cell lines JM and HSB-2. Southern blot analysis of DNA from LK63 suggested that the HEK gene was neither amplified nor rearranged in the LK63 tumor. PMID- 1311847 TI - Evidence for a membrane defect in Alzheimer disease brain. AB - To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease. PMID- 1311846 TI - Expression of nerve growth factor in vivo from a defective herpes simplex virus 1 vector prevents effects of axotomy on sympathetic ganglia. AB - Sympathetic neurons in the superior cervical ganglion (SCG) of adult rats depend on target-derived nerve growth factor (NGF) for maintenance of tyrosine hydroxylase (TH) levels and the noradrenergic neurotransmitter system. Axotomy of a SCG results in NGF deprivation, causing a decline in TH activity; continuous local application of NGF can prevent this decline in TH activity. We now report that injection of a defective herpes simplex virus 1 vector that expresses NGF (pHSVngf) into a SCG can prevent the decline in TH activity that follows axotomy. SCG of adult rats were injected with either pHSVngf virus or pNFlac virus, which expresses Escherichia coli beta-galactosidase. Analysis of RNA from pHSVngf infected SCG indicated that the NGF gene was efficiently transcribed and processed. Furthermore, 4 days after pHSVngf injection animals underwent axotomy of the virus-injected SCG. After another 10 days, animals were sacrificed and both the injected-axotomized and contralateral control ganglia were assayed for TH activity. Axotomy of SCG injected with pNFlac virus produced a 50% decline in TH activity relative to control ganglia (P = 0.02). In contrast, SCG injected with pHSVngf virus did not show a decline in TH activity following axotomy; instead, these ganglia manifested an 18% increase in TH levels relative to control ganglia. These data demonstrate that herpes simplex virus 1 vectors can be used to modify neuronal physiology in vivo; specifically, expression of a critical gene product by neural cells that do not normally produce it has potential applications for gene therapy. PMID- 1311848 TI - A protein required for RNA processing and splicing in Neurospora mitochondria is related to gene products involved in cell cycle protein phosphatase functions. AB - The Neurospora crassa cyt-4 mutants have pleiotropic defects in mitochondrial RNA splicing, 5' and 3' end processing, and RNA turnover. Here, we show that the cyt 4+ gene encodes a 120-kDa protein with significant similarity to the SSD1/SRK1 protein of Saccharomyces cerevisiae and the DIS3 protein of Schizosaccharomyces pombe, which have been implicated in protein phosphatase functions that regulate cell cycle and mitotic chromosome segregation. The CYT-4 protein is present in mitochondria and is truncated or deficient in two cyt-4 mutants. Assuming that the CYT-4 protein functions in a manner similar to the SSD1/SRK1 and DIS3 proteins, we infer that the mitochondrial RNA splicing and processing reactions defective in the cyt-4 mutants are regulated by protein phosphorylation and that the defects in the cyt-4 mutants result from failure to normally regulate this process. Our results provide evidence that RNA splicing and processing reactions may be regulated by protein phosphorylation. PMID- 1311849 TI - Phase-separation inhibitors and prevention of selenite cataract. AB - The variation of the phase-separation temperature (Tc) was studied in lenses during formation of cataracts induced by a subcutaneous injection of sodium selenite. In normal control animals, the Tc decreased monotonically with increasing age. Approximately 2 days after administration of the selenite the Tc decreased sharply to a minimum, and then at day 4 the Tc increased dramatically toward body temperature. Mature irreversible cataracts formed approximately 6 days after injection of the selenite. Intraperitoneal administration of WR-77913, a phase-separation inhibitor, prevented the abnormal variation of Tc in vivo. When injected into control animals without selenite, WR-77913 produced no abnormal variation in Tc. The results confirm that Tc is a sensitive measure of early changes in the lens and that opacification associated with abnormal variation in Tc can be prevented in vivo by using a phase-separation inhibitor. PMID- 1311850 TI - Oligonucleotide-directed site-specific mutagenesis in Drosophila melanogaster. AB - An efficient technique has been developed for performing in vivo site-directed mutagenesis in Drosophila melanogaster. This procedure involves directed repair of P-element-induced DNA lesions after injection of a modified DNA sequence into early embryos. An oligonucleotide of 50 base pairs, whose sequence spans the P element insertion site, mediates base replacement in the endogenous gene. Restriction mapping, DNA sequencing, and polymerase chain reaction analysis demonstrate that base substitutions present in an injected oligonucleotide are incorporated into genomic sequences flanking a P insertion site in the white gene. This analysis suggests that progeny bearing directed mutations are recovered with a frequency of about 0.5 x 10(-3). Because Drosophila remains a premier organism for the analysis of eukaryotic gene regulation, this system should find strong application in that analysis as well as in the analysis of DNA recombination, conversion, repair, and mutagenesis. PMID- 1311851 TI - Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site. AB - The inhibitory glycine receptor (GlyR) is a member of the ligand-gated ion channel receptor superfamily. Glycine activation of the receptor is antagonized by the convulsant alkaloid strychnine. Using in vitro mutagenesis and functional analysis of the cDNA encoding the alpha 1 subunit of the human GlyR, we have identified several amino acid residues that form the strychnine-binding site. These residues were identified by transient expression of mutated cDNAs in mammalian (293) cells and examination of resultant [3H]strychnine binding, glycine displacement of [3H]strychnine, and electrophysiological responses to the application of glycine and strychnine. This mutational analysis revealed that residues from two separate domains within the alpha 1 subunit form the binding site for the antagonist strychnine. The first domain includes the amino acid residues Gly-160 and Tyr-161, and the second domain includes the residues Lys-200 and Tyr-202. These results, combined with analyses of other ligand-gated ion channel receptors, suggest a conserved tertiary structure and a common mechanism for antagonism in this receptor superfamily. PMID- 1311852 TI - Molecular cloning and sequence of cDNA encoding the pyrophosphate-energized vacuolar membrane proton pump of Arabidopsis thaliana. AB - The energy-dependent transport of solutes across the vacuolar membrane (tonoplast) of plant cells is driven by two H+ pumps: a vacuolar ("V-type") H(+) ATPase (EC 3.6.1.3) and a H(+)-translocating (pyrophosphate-energized) inorganic pyrophosphatase (H(+)-PPase; EC 3.6.1.1). The H(+)-PPase, like the V-type H(+) ATPase, is abundant and ubiquitous in the vacuolar membranes of plant cells, and both enzymes make a substantial contribution to the transtonoplast H(+) electrochemical potential difference. Here, we report the cloning and sequence of cDNAs encoding the tonoplast H(+)-PPase of Arabidopsis thaliana. The protein predicted from the nucleotide sequence of the cDNAs is constituted of 770 amino acids and has a molecular weight of 80,800. It is a highly hydrophobic integral membrane protein, and the structure derived from hydrophilicity plots contains at least 13 transmembrane spans. Since the tonoplast H(+)-PPase appears to be constituted of one polypeptide species and genomic Southern analyses indicate that the gene encoding the Mr 80,800 polypeptide is present in only a single copy in the genome of Arabidopsis, it is suggested that the H(+)-PPase has been cloned in its entirety. The lack of sequence identities between the tonoplast H(+)-PPase and any other characterized H+ pump or PPi-dependent enzyme implies a different evolutionary origin for this translocase. PMID- 1311853 TI - Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants. AB - Salmonella typhimurium penetrate intestinal epithelial cells during infection. In vitro studies reveal that the availability of oxygen during bacterial growth decreases their capacity to adhere to and enter cultured epithelial cells. To identify S. typhimurium genes involved in epithelial cell entry, mutants were selected that entered HEp-2 cells when grown under repressing, aerobic culture conditions. Two types of transposons were used to generate bacterial mutations- transposons that disrupt genes (Tn10 and Tn5) and one transposon (Tn5B50) that, in addition to disrupting genes, can cause constitutive expression of genes from the neo promoter at one end of the transposon. Three classes of mutations were found that increased the ability of aerobically grown S. typhimurium to enter HEp 2 cells. One class of mutations disrupts the che operons and results in a nonchemotactic phenotype. The second class of mutations revealed that defects in rho, which encodes an essential transcription termination factor, result in hyperinvasiveness. The third class of mutations was obtained only from mutagenesis with Tn5B50, suggesting that their increased invasiveness is due to constitutive expression of a gene(s) from the exogenous neo promoter. Analysis of this third class of mutations identified a S. typhimurium locus hil (hyperinvasion locus), which is essential for bacterial entry into epithelial cells. The results suggest that hil encodes an invasion factor or an activator of invasion factor expression. hil maps between srl and mutS near minute 59.5 of the S. typhimurium chromosome, a region adjacent to other loci that have been identified as required for S. typhimurium invasiveness and virulence. PMID- 1311855 TI - Altering the insertional specificity of a Drosophila transposable element. AB - Vectors derived from the Drosophila P element transposon are widely used to make transgenic Drosophila. Insertion of most P-element-derived vectors is nonrandom, but they exhibit a broad specificity of target sites. During experiments to identify cis-acting regulatory elements of the Drosophila segmentation gene engrailed, we identified a fragment of engrailed DNA that, when included within a P-element vector, strikingly alters the specificity of target sites. P-element vectors that contain this fragment of engrailed regulatory DNA insert at a high frequency near genes expressed in stripes. PMID- 1311854 TI - Solution conformation of the major adduct between the carcinogen (+)-anti benzo[a]pyrene diol epoxide and DNA. AB - We have synthesized, separated, and purified approximately 10 mg of a deoxyundecanucleotide duplex containing a single centrally positioned covalent adduct between (+)-anti-benzo[a]pyrene (BP) diol epoxide and the exocyclic amino group of guanosine. Excellent proton NMR spectra are observed for the (+)-trans anti-BP diol epoxide-N2-dG adduct positioned opposite dC and flanked by G.C pairs in the d[C1-C2-A3-T4-C5-(BP)G6-C7-T8-A9-C10-C11].d[12- G13-T14-A15-G16-C17-G18 A19-T20-G 21-G22] duplex +ADdesignated (BP)G.C 11-mer+BD. We have determined the solution structure centered about the BP covalent adduct site in the (BP)G.C 11 mer duplex by incorporating intramolecular and intermolecular proton-proton distance bounds deduced from the NMR data sets as constraints in energy minimization computations. The BP ring is positioned in the minor groove and directed toward the 5' end of the modified strand. One face of the BP ring of (BP)G6 is stacked over the G18 and A19 sugar-phosphate backbone on the partner strand and the other face is exposed to solvent. A minimally perturbed B-DNA helix is observed for the d[T4-C5-(BP)G6-C7-T8].d[A15-G16-C17-G18-A19] segment centered about the adduct site with Watson-Crick alignment for both the (BP)G6.C17 pair and flanking G.C pairs. A widening of the minor groove at the adduct site is detected that accommodates the BP ring whose long axis makes an angle of approximately 45 degrees with the average direction of the DNA helix axis. Our study holds future promise for the characterization of other steroisomerically pure adducts of BP diol epoxides with DNA to elucidate the molecular basis of structure-activity relationships associated with the stereoisomer-dependent spectrum of mutational and carcinogenic activities. PMID- 1311856 TI - Hormonal regulation of major histocompatibility complex class I genes in rat thyroid FRTL-5 cells: thyroid-stimulating hormone induces a cAMP-mediated decrease in class I expression. AB - Thyrocytes normally express major histocompatibility complex (MHC) class I, but not class II, cell surface antigens. A rat thyrocyte cell line, FRTL-5, also expresses MHC class I antigens, in addition to a variety of thyroid-specific genes. Treatment of FRTL-5 thyrocytes with physiological concentrations of thyroid-stimulating hormone (TSH) has been shown to induce increased expressed of thyroglobulin and thyroid peroxidase but to simultaneously decrease expression of the TSH receptor. The reduction in TSH receptor expression by TSH is cAMP mediated. In the present study, it is demonstrated that, in thyrocytes treated with TSH, MHC class I expression decreases concomitant with the decrease in TSH receptor expression. This decreased expression is evidenced by reduced cell surface levels of MHC class I antigens, by reduced steady-state RNA levels, and by reduced transcription of the class I genes. TSH-mediated reduction of MHC class I gene transcription in FRTL-5 cells was mapped to a region within 135 base pairs of the promoter. PMID- 1311857 TI - Proliferation of totipotent hematopoietic stem cells in vitro with retention of long-term competitive in vivo reconstituting ability. AB - Marrow cells from male mice pretreated with 5-fluorouracil were infected with helper-free neomycin-resistant (neor) recombinant retrovirus and then used to initiate long-term cultures (LTC) on irradiated adherent marrow feeder layers. Four weeks later LTC cells were harvested and injected into lethally irradiated female recipients either alone or together with 2 x 10(5) female marrow cells with selectively compromised long-term repopulating potential to assay for totipotent and competitive repopulating units (CRU), respectively. A total of 46 unique clones were detected in recipients 5 wk to 7 mo after transplant. Half of these clones (22 of 46) included both lymphoid and myeloid progeny. Eight of the 22 lympho-myeloid clones were represented in multiple recipients, in some cases after injection of limiting numbers of CRU, thus indicating repopulation from sibling totipotent stem cells generated during the initial 4-wk period in LTC. Serial analysis of cells released into the nonadherent fraction of LTC for up to 7 wk provided additional evidence of the continuing proliferation in LTC of totipotent stem cells with long-term repopulating potential. The frequency of CRU determined from limiting-dilution analyses of LTC-derived cells was the same for recipients analyzed at 5 wk or 7 mo after transplantation and was also the same whether marrow or thymus repopulation was assessed. These assays showed that concurrent with the expansion of some totipotent cells revealed by retroviral marking, there was a slow but net 6.5-fold decrease in total CRU numbers after 4 wk in LTC. These results show the capacity of some totipotent hematopoietic stem cells to be maintained and amplified over extensive time periods in vitro without diminution of their long-term in vivo repopulating potential. These results also set the stage for analogous studies of human stem cell selection and expansion in vitro, which may be important for future gene therapy protocols. PMID- 1311858 TI - Opioid enhancement of evoked [Met5]enkephalin release requires activation of cholinergic receptors: possible involvement of intracellular calcium. AB - Previous work from this laboratory has shown that the electrically evoked release of enkephalin from the guinea pig myenteric plexus is regulated by an opiate receptor-mediated, concentration-dependent mechanism. Low concentrations (nanomolar) of opioids enhance release, whereas higher concentrations (10-100 nM) inhibit release. Each opioid effect is mediated by a different guanine nucleotide binding protein. We now demonstrate that activation of cholinergic receptors in the myenteric plexus is a prerequisite for opioid excitatory effects, but not inhibitory effects, on enkephalin release. Pretreatment with the muscarinic cholinergic receptor antagonist atropine abolishes the opioid facilitation of stimulated enkephalin release but does not alter the inhibition of release that is observed with higher concentrations of opioid agonist. Exposure to the calcium ionophore A23187 overcomes the abolishment of opioid enhancement of enkephalin release produced by cholinergic receptor blockade. In tissue treated with both atropine and A23187, the magnitude of the opioid enhancement of release is indistinguishable from that observed in untreated preparations. This suggests that the lack of stimulation-induced generation of elevated cytosolic calcium is responsible for the abolishment of facilitory opioid effects when cholinergic receptors are blocked. The known coupling of muscarinic receptors to phospholipase C activation and the generation of inositol trisphosphate (which elevates cytosolic calcium) could suggest that this second messenger is critical for the manifestation of opioid facilitation of enkephalin release. PMID- 1311859 TI - cis-urocanic acid down-regulates the induction of adenosine 3',5'-cyclic monophosphate by either trans-urocanic acid or histamine in human dermal fibroblasts in vitro. AB - It has been demonstrated that UVB radiation (290-320 nm) suppresses mammalian cell-mediated immunity by effecting the trans to cis isomerization of urocanic acid (UCA) in the stratum corneum, the uppermost layer of the skin. Trans urocanic acid has been shown to be the photoreceptor for UVB-induced immune suppression and the cis-isomer has been demonstrated to be immunosuppressive. Little is known, however, about how the isomerization of UCA may affect the proximal or distal cells of the skin or the immune system. We report here that trans-UCA is biologically active in vitro in human dermal fibroblasts, inducing adenyl cyclase as measured by cAMP (adenosine 3',5'-cyclic monophosphate) formation in a dose-dependent manner similar to the action of histamine. Trans UCA and histamine stimulate 50% of maximum activity at concentrations of 3.3 microM and 13.8 microM respectively. Cis-UCA does not increase cAMP in these human fibroblasts but actively down regulates the increase of cAMP induced by either histamine or trans-UCA. Cis-UCA down regulated the histamine response by 75% and the trans-UCA response by 60% at a concentration range of 1 mM to 1 nM. The trans-UCA induction of cAMP can also be downregulated with an H2 histamine receptor antagonist cimetidine. These results support the hypothesis that a cellular target for cis-UCA is the dermal fibroblast and the effects reported here may represent the initial biochemical and cellular event for UVB-induced immune suppression i.e. the immediate step following the isomerization of trans to cis-UCA is the down regulation of cAMP by cis-UCA. Regulation of such an important second messenger such as cAMP could then allow cascading signals to occur, leading to immune suppression. PMID- 1311860 TI - Pheophorbide a-induced photo-oxidation of cytochrome c: implication for photodynamic therapy. AB - Pheophorbide a-induced photo-oxidation, in vitro, of cytochrome c oxidase and cytochrome c results in irreversible modifications to both protein components. Photo-oxidation of cytochrome c, as exhibited by change in its heme oxidation state, displays exponential kinetics and is detected with a lag period. Both the photo-induced inactivation of the enzyme, and destruction of the substrate ability of cytochrome c occur as complex multi-process events. Under similar experimental conditions, the loss of the substrate capability of cytochrome c develops approximately three times faster than inactivation of the enzyme. The slight lag in the photo-oxidation of cytochrome c is due to pheophorbide a induced superoxide production. However, the relative amount of photo-oxidant produced is considerably more effective than the cytochrome c reducing capacity of the superoxide. Neither hydroxyl radical nor hydrogen peroxide are involved in the photo-oxidation of the heme function. The possibilities of heme oxidation by a singlet oxygen mediated pathway or direct electron abstraction involving the heme or apoprotein are not excluded. It is proposed that a multi-site oxidation of numerous reduced energy cofactors within cells may augment collateral enzyme inactivation in maximizing photosensitizer-induced cytotoxicity. Accordingly, amphipathic photosensitizers, capable of accessing both lipid and aqueous compartments containing reduced cofactors, may be more effective agents for photodynamic therapy than those which exhibit a high specificity of subcellular localization. PMID- 1311861 TI - Cell density dependence of ultraviolet light enhanced reactivation of Herpes simplex type I and the large plaque effect in C3H/10T1/2 mouse fibroblasts. AB - C3H/10T1/2 mouse fibroblasts were grown to different cell densities either by plating at low density and allowing different growth periods, or by plating at a series of increasing densities and allowing the same growth period. These plates were UV irradiated at 7.5 J/m2 or mock irradiated and 24 h later infected with UV irradiated Herpes simplex type I virus which had been UV irradiated at 50 or 125 J/m2 or mock irradiated. The numbers and sizes of plaques were measured and these data used to calculate the extent of UV-enhanced host cell reactivation, the capacity enhancement, the large plaque effect (LPE) and the small plaque effect (SME). The influence of cell density on these phenomena was similar for both series of density experiments. Ultraviolet-enhanced host cell reactivation could be demonstrated only for cultures of lower density. The capacity of the cells for Herpes simplex type I virus decreased with cell density, but UV irradiated cells showed an increase in capacity with cell density. Plaque sizes decreased in all cases with cell density but the LPE and SPE were not significantly altered. The greatest variation in the above parameters occurred just as the cells were approaching confluence, where most host cell reactivation experiments are carried out. We conclude that the reproducibility of such experiments depends critically on cell density, a dependence which may be relevant to mechanistic interpretations of the UV-dependent phenomena. PMID- 1311862 TI - Radiation-induced heart disease: morphology, changes in catecholamine synthesis and content, beta-adrenoceptor density, and hemodynamic function in an experimental model. AB - To study further the pathophysiology of radiation-induced cardiomyopathy, we investigated resting hemodynamics, myocardial catecholamine synthesis and storage, and beta-adrenoceptor density after local heart irradiation. In Wistar rats, a radiation dose of 20 Gy eventually leads to compromised myocardial function which is characterized by a reduction in cardiac output to 43 +/- 11% and in the left ventricular ejection fraction to 66 +/- 7.5%, and an increase in the left ventricular end-diastolic volume to 187 +/- 17% of control values. This reduction in function is correlated with focal degeneration of 23 +/- 4% of the myocardium. Measurement of tyrosine hydroxylase activity and catecholamine content revealed that catecholamine biosynthesis is unchanged in the adrenals but is significantly reduced in the hearts of irradiated animals, while cardiac beta adrenoceptor density is increased to about 140% of that in age-matched controls. This is in contrast to findings in dilated or ischemic cardiomyopathy. Time course studies showed that the development of myocardial degeneration starts simultaneously with the decrease in cardiac output and ejection fraction and the increase in beta-adrenoceptors at 50-80 days postirradiation. Myocardial degeneration is maximal in extent and severity at 100 days and does not progress thereafter. Cardiac output decreases at 80-100 days postirradiation to 60 +/- 7% of control values. A significant further decrease is seen only when congestive heart failure becomes manifest at 249 +/- 21 days after 20 Gy. Thus there is a delay between structural myocardial injury and hemodynamic deterioration which could be due to a compensatory increase in beta-adrenoceptor density during the initial stages of the cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311863 TI - The v-src oncogene may not be responsible for the increased radioresistance of hematopoietic progenitor cells expressing v-src. AB - Infection of the IL-3-dependent, myeloid progenitor cell line 32D cl 3 with murine retroviruses that contain either the wild-type or a temperature-sensitive mutant v-src can render these cells growth-factor independent. These cells also became resistant to gamma irradiation administered at the low-dose rate of 0.05 Gy/min, which is used clinically. The v-src-dependent nature of resistance to gamma irradiation was examined by studying four clones of 32D cl 3 cells that had been infected with a retrovirus carrying the tsLA31A mutant of v-src. The tyrosine-specific kinase activity of this mutant is dramatically reduced at the nonpermissive temperature of 39 degrees C. Cells transformed by v-src and grown at either 34 or 39 degrees C, in the presence or absence of IL-3, demonstrated a significantly higher D0 compared to parental cells examined under identical conditions. In addition, expression of v-src abrogated the synergistic killing effect of heat and gamma irradiation. The D0 of parental 32D cl 3 cells kept at 39 degrees C after gamma irradiation was reduced significantly compared to the D0 of these cells kept at 34 degrees C. This contrasts with data from 32D cl 3 cells infected with either the wild-type v-src or the temperature-sensitive mutant, neither exhibited a synergistic effect in the D0 at either 34 or 39 degrees C. Therefore, while continuous expression of a v-src gene product is required for maintenance of the growth-factor-independent state, v-src does not appear to be responsible for the increased gamma-radiation resistance of these cells at low dose rate. PMID- 1311864 TI - Thromboxane A2 mimetic U46619 stimulates ciliary motility of rabbit tracheal epithelial cells. AB - To elucidate whether thromboxane A2 (TxA2), one of the important arachidonic acid metabolites that may play a role in the development of airway inflammation, affects respiratory ciliary motility and, if so, what the mechanism of action is, we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium in response to U46619, a TxA2 mimetic agonist, by a photoelectric method. Addition of U46619 (10(-5) M) increased CBF from 17.7 +/- 0.7 to 22.8 +/- 1.4 Hz (mean +/- SE, p less than 0.01) within 5 min, which was followed by a decline to the baseline value by 10 min. This effect was concentration-dependent, the maximal increase from the baseline value and the drug concentration required to produce a half-maximal effect (EC50) being 26.9 +/- 4.6% (p less than 0.01) and 3 x 10(-7) M, respectively. The U46619-induced increase in CBF was abolished by SQ29548, and TxA2 receptor antagonist, and inhibited by verapamil, a Ca(2+)-entry blocker, and H-7, a protein kinase C inhibitor. These results suggest that TxA2 stimulates ciliary motility through the activation of airway epithelial TxA2 receptors, and that this effect may be exerted from Ca(2+)-influx and protein kinase C. PMID- 1311865 TI - [Vitamin D poisoning in infants: a preventable cause of hypercalciuria and nephrocalcinosis]. AB - The established prophylaxis for vitamin D-deficient rickets today is 400 IU vitamin D3 given daily during the first year of life. With this regimen, vitamin D intoxication is a rare event. Nevertheless, we have recently seen 4 infants with vitamin D intoxication after a so called "stoss" prophylaxis, i.e. twice 300,000 units (7.5 mg) vitamin D3 orally within 4 weeks. One patient presented with failure to thrive due to marked hypercalcemia (3.9 mmol/l) and nephrocalcinosis, 2 patients showed medullary nephrocalcinosis on ultrasonography and one patient had gross hematuria and spontaneous passage of a calculus. Three patients had massive hypercalciuria (calcium/creatinine ratio 1.8-4.8 mol/mol, normal less than 1). The 25 (OH) vitamin D3 plasma levels, measured only in 2 patients, were strikingly increased (270 and 158 nmol/l, respectively, normal 25 80). Urinary calcium excretion slowly decreased to normal values on a low calcium diet and high fluid intake. Nephrocalcinosis, however, persisted in 2 patients and showed a slight progression ultrasonographically in one patient. The short time interval between vitamin D administration and onset of symptoms and the subsequent clinical course provide strong evidence that hypercalciuria and nephrocalcinosis were due to vitamin D "stoss" prophylaxis in all four cases. In conclusion, there is no indication for vitamin D "stoss" prophylaxis for vitamin D-deficient rickets in infants. Vitamin D intoxication still has to be considered as a possible cause of hypercalciuria. PMID- 1311866 TI - OSI: better the devil you know? PMID- 1311867 TI - Kaposi's sarcoma gives on key fronts. PMID- 1311868 TI - Hepatic resection in patients with cirrhosis and hepatocellular carcinoma. AB - Hepatic resection can be performed safely in carefully selected patients with cirrhosis. To minimize morbidity and mortality, it is essential to reliably estimate functional hepatic reserve and the extent of tumor before resection is performed. Child's classification is a reliable predictor of long term survival, but a more sensitive measure of hepatic function is needed to predict early morbidity and mortality. Child's classification can also be used to stratify patients and exclude those at high risk from hepatic resection. Promising predictors of operative mortality focus on the mitochondrial function of hepatocytes and include cytochrome a (+a3) contents and the redox tolerance index. Patients with advanced cirrhosis are not candidates for extensive hepatic resection and require careful evaluation before consideration for any hepatic resection. In patients with well-compensated cirrhosis and unifocal tumors, the procedure of choice is an anatomic resection of the tumor. If tumor size and location allows, a segmentectomy offers the best outcome, minimizing postoperative liver dysfunction while offering a long term outcome not dissimilar to a major liver resection. In highly selected patients with incidental tumors, a central tumor and perhaps in patients with multifocal hepatocellular carcinoma, hepatic transplantation may be of benefit. By using the appropriate predictors of hepatic function, refined surgical techniques and optimal postoperative care, a mortality rate of less than 10 per cent is achievable in cirrhotic patients with hepatocellular carcinoma who require resection. PMID- 1311869 TI - Postoperative femoral neuropathy. AB - Postoperative femoral neuropathy is more common than it is generally appreciated. It can occur by a number of different mechanisms after a wide variety of operations as a result of either direct or indirect injury. Most instances occur after abdominopelvic operations and are associated with the placement of self retaining retractors. A large body of evidence suggests that, in these patients, nerve compression by the lateral blades of the retractor is the cause. There is, however, evidence that the intrapelvic portion of the nerve is particularly susceptible to ischemia. Usually, there is a mild sensorimotor disturbance and the diagnosis is easily made by accurate physical examination during the early postoperative period. A diminished or absent knee jerk is the most reliable clinical sign. Recovery is the rule; it occurs usually from a few weeks to months. During this time, physiotherapy may be beneficial. Occasionally the lesion may be severe or prolonged, or both. In these instances, EMG studies are justified, not only to allay the fears of patients and physicians, but to evaluate the progress of the lesion over time. With the exception of certain unusual instances, this potentially debilitating postoperative complication can be avoided by careful placement of self-retaining retractors. PMID- 1311870 TI - [Primary tumor volume and prognosis in bronchial carcinoma]. AB - Lymph node involvement and histologic type are well known and accepted as prognostic factors for bronchial carcinoma. The role of the primary tumor volume has been but rarely examined. However, it is accepted that there is a clear correlation between primary tumor mass and the level of tumor cell dissemination. Therefore primary tumor volume can be a useful prognostic indicator especially for those tumors of which no evidence of metastases can be proved even with CT or MR. In case of 1022 patients, having been received a tumor dose more than 5600 cGys (on the 80% isodose curve), if metastatic including the primary lymph nodes, we examined the correlation between histologic type, lymph node involvement, primary tumor volume and overall survival, response on chest X-ray films, and tumor destruction in autopsy materials, respectively. We found: 1. There was a strong correlation, especially in N0-cases, between primary tumor volume and overall survival, in all histologic types. 2. Small regional metastatic tumors (N1, N2) had a better prognosis than that of great tumors with no metastases (N0), in all histologic types. 3. Small adenocarcinomas and large-cell tumors without lymph node involvement had a better prognosis than that of squamous cell tumors of the same stage. 4. In 222 cases of T2N0-tumors five-year overall survival was 15.3%, in 43 cases of large-cell tumors and adenocarcinomas 29%, respectively. CONCLUSION: Primary tumor volume is an important prognostic factor and can be easily and objectively evaluated. PMID- 1311871 TI - Liver ischemia for hepatic resection: where is the limit? AB - BACKGROUND: A consecutive series of 50 patients who submitted to 53 hepatic resections with use of continuous normothermic liver ischemia is reported. METHODS: Portal triad clamping has been used in 28 cases, with associated inferior vena caval clamping above and below the liver (hepatic vascular exclusion) in 25 patients. The size of the tumor required major hepatic resection in 38 cases (71.7%). Malignant tumors (83%) were the most common indication for liver resection. Patients were placed in three groups according to the duration of liver ischemia: group A, less than 30 minutes (9 patients); group B, 30 to 60 minutes (29 patients); and group C, 60 or more (15 patients). RESULTS: No differences in mortality rates (5.7% in the entire series and 0% in group C) and morbidity rate could be shown. No significant difference was found in postoperative liver test results, and no persistent alteration remained thereafter. Liver biopsy at 6 and 12 months after operation did not reveal any chronic damage. Liver capability to regenerate was maintained as documented by postoperative computerized tomography scan or magnetic resonance imaging. CONCLUSIONS: Because interruption of hepatic blood flow in normothermia is safe for at least 60 minutes (up to 85 minutes in this study), vascular clamping is recommended for hazardous liver resections to minimize blood loss, which appears to be the main factor of death and morbidity. PMID- 1311872 TI - Functional role of the preserved rectal cuff in ileoanal anastomosis. AB - BACKGROUND: This study included 16 patients without complications, eight patients with ulcerative colitis, and eight patients with familial adenomatous polyposis. All patients underwent colectomy, mucosal proctectomy, and ileoanal anastomosis in the jackknife position with complete removal of the rectoanal columnar mucosa above the dentate line (IAA) through the anus. METHODS: The patients were divided into two groups: eight patients with the rectal cuff about 7 cm from the dentate line, "the medium-cuff group," and eight patients who underwent resection of the rectal stump above the levator, leaving a cuff of 2 cm, "the minimum-cuff group." RESULTS: In the medium-cuff group the percent recovery of maximum resting pressure and maximum squeeze pressure 12 months after IAA were not significantly decreased, the rectoanal inhibitory reflex recovered in 87.5% of patients, and all patients regained continence. In the minimum-cuff group, however, the percent recovery for both pressures remained significantly reduced, the reflex never recovered, and only 25% of the patients were continent after 12 months (p less than 0.05). There was no significant difference in capacity or distensibility of the ileal pouch between the groups. CONCLUSIONS: These results indicate that the medium-cuff method was associated with a superior functional result compared with the minimum-cuff method in the early postoperative period and the cuff in the lower rectum connected with the visceral nerves should be preserved to achieve better bowel function in the patient undergoing IAA. The initial mucosectomy through the anus in the prone jackknife position is useful for this purpose. PMID- 1311873 TI - Hypophosphatemia after major hepatic resection. AB - METHODS: We performed a retrospective study of 44 patients who underwent right or extended right hepatic lobectomy to determine the incidence and significance of hypophosphatemia after major hepatic resection. RESULTS: The postoperative serum phosphate level (measured as inorganic phosphorus) dropped in all 44 patients studied. Profound hypophosphatemia (less than 1.0 mg/dl) was significantly (p less than 0.001) associated with the frequent development of major postoperative complications (cardiorespiratory, five cases; infections, four cases; hemorrhage, one case; and liver failure, one case). Factors such as extent of liver resection, blood loss, blood or plasma transfusion, postoperative bilirubin level, and preexisting liver diseases showed no significant correlation with the nadir inorganic phosphorous level. Use of aluminum-containing antacids caused a further drop of the serum values (p less than 0.05). Early phosphorous replacement showed a significant protective effect (p less than 0.05), with higher serum levels and fewer major complications. CONCLUSIONS: These observations affirm the importance of frequent monitoring and replacement of phosphate after major hepatic resection. PMID- 1311874 TI - Oxygen free radicals are required for ischemia-induced leukotriene B4 synthesis and diapedesis. AB - Hind limb ischemia and reperfusion have been shown to result in high plasma levels of leukotriene B4 (LTB4) and polymorphonuclear neutrophil (PMN) sequestration in the pulmonary microvasculature. This study tests whether LTB4 is derived from PMNs and its role in mediating ischemic plasma-induced diapedesis. Plasma derived from rabbit hind limbs after 3 hours of tourniquet ischemia and 10 minutes of reperfusion (n = 6) showed an increased LTB4 level of 560 pg/ml, higher than sham plasma values of 106 pg/ml (p less than 0.05). Introduction of ischemic plasma in abraded skin chambers placed on the dorsum of normal rabbits (n = 6) led after 3 hours to PMN diapedesis of 1175 PMN/mm3, associated with a further increase in LTB4 levels to 820 pg/ml (both p less than 0.05). In contrast, ischemic plasma derived from neutropenic animals (n = 4; nitrogen mustard, 2 mg/kg; PMNs less than 30/mm3) contained lower levels of LTB4, 160 pg/ml (p less than 0.05). When introduced in skin chambers in normal rabbits (n = 4), this plasma induced accumulations of only 163 PMN/mm3, accompanied by a smaller increase in LTB4 levels in the blister fluid after 3 hours, 397 pg/ml (both p less than 0.05). A correlation was found between LTB4 levels in ischemic plasma and PMN accumulations in blister fluid (r = 0.92; p less than 0.05). Intravenous pretreatment of rabbits (n = 4) used in the blister chamber bioassay with the LT receptor antagonist FPL-55712, 40 micrograms/kg/hr, attenuated diapedesis induced by ischemic and ischemic-neutropenic plasma, 103 and 35 PMN/mm3, respectively (both p less than 0.05). Pretreatment with superoxide dismutase, 1500 units/kg, and catalase, 5000 units/kg, both conjugated to polyethylene glycol (n = 4), prevented ischemic plasma-induced LTB4 synthesis, as well as ischemic plasma-induced diapedesis, 12 PMN/mm3 (p less than 0.05). Finally, pretreatment with allopurinol, 25 mg/kg, was similarly effective in preventing LTB4 synthesis and PMN migration. These data suggest that oxygen free radicals are essential for ischemia-induced PMN synthesis of LTB4 that in turn mediates their diapedesis. PMID- 1311875 TI - A new method of intraoperative cytodiagnosis for more precisely locating the occult neoplasms of the pancreas. AB - We have done endoscopic retrograde pancreatography-aspiration cytology for 81 consecutive patients in whom there had been neither pancreatic mass nor duct stenosis; cancer cells were detected in four cases (5%). This report reviews a new method of intraoperative cytodiagnosis, which was done for these four cases, to locate the original lesion of the cancer cells. This method involved dividing the pancreatic neck at a right angle to the main pancreatic duct. A catheter was then inserted in both the caudal and cranial ducts of Wirsung. With the aid of an intravenous injection of secretin, pure pancreatic secretions were collected separately and used for intraoperative cytodiagnosis. With this method, all four occult neoplasms of the pancreas were correctly identified as to whether they were located in the cranial, caudal, or both portions. In one case in which carcinoma in situ extended throughout the entire pancreas, total pancreatectomy had been indicated by the positive results obtained from both portions. Likewise, in the other three cases in which, the occult neoplasms were limited to the cranial or caudal pancreas, either a Whipple procedure (one case) or a caudal pancreatectomy (two cases) had been quite correctly indicated. Since this method is simple, safe, and reliable, it is beneficial to the patient with occult neoplasm, because it prevents blind resection of the entire pancreas without any fear of leaving the neoplastic lesion behind. PMID- 1311876 TI - Low risk of viral infection after administration of vapor-heated factor VIII concentrate. International Investigator Group. AB - A multicenter prospective study was carried out to evaluate whether a vapor heated factor VIII concentrate transmitted blood-borne viral infections over a surveillance period of 15 months. Thirty-five patients with hemophilia and von Willebrand disease who had never received any blood components were treated. Twenty-eight were analyzed and found not to have non-A, non-B hepatitis. Sera from 20 of these 28 patients were also tested for the antibody to the hepatitis C virus. None had sero-converted during the follow-up period. None of the patients analyzed developed markers of the hepatitis B virus (n = 17) or the human immunodeficiency virus (n = 31). This vapor-heated factor VIII concentrate carries a low risk of transmitting hepatitis and human immunodeficiency virus infection. PMID- 1311877 TI - Influence of C4B null genes on cytomegalovirus antibody titers in healthy blood donors. AB - C4B null genes (C4B*Q0) have been found with increased frequency in persons with viral diseases, including hepatitis and human immunodeficiency virus infection. Whether a relationship might exist between the presence of C4B*Q0 and antibodies to cytomegalovirus (CMV) was investigated. Fifty blood donors who were seropositive for CMV antibodies and 101 healthy nondonors were C4-allotyped with electrophoresis immunofixation. CMV-seropositive sera were titrated for CMV IgG specific antibody by enzyme-linked immunosorbent assay, and serum IgG levels were assayed by rate nephelometry. C4B*Q0 was higher in the CMV antibody-positive group than in nondonors (p = 0.05), but the increase was most significant (p = 0.028) in donors with the highest titers of CMV antibodies. There was poor correlation (r = 0.015) between CMV titers and plasma IgG levels. Serum C4B levels were lower in CMV antibody-positive donors with one C4B null gene than in matched nondonors or nondonors not having any null genes. PMID- 1311878 TI - Nitric oxide takes centre-stage with newly defined roles. PMID- 1311879 TI - Ca2+ influx following receptor activation. PMID- 1311880 TI - Pharmacological strategies in CNS trauma. AB - Delayed biochemical changes play an important role in tissue damage resulting from traumatic injuries to the central nervous system. Identification of such 'secondary' injury factors has led to the development of various pharmacological strategies aimed at limiting this progressive tissue destruction. In this review, Alan Faden and Steven Salzman discuss the pharmacological approaches that have the most experimental support. These include corticosteroids, antioxidants and free-radical scavengers, modulators of arachidonate metabolism, gangliosides, monoamine modulators, opioid receptor antagonists, TRH and its analogs, NMDA receptor antagonists, Ca2+ channel antagonists and platelet-activating factor antagonists. PMID- 1311881 TI - [Angiotensin I converting inhibitors in connection with anesthesia and surgery]. AB - The renin angiotensin system is activated during anaesthesia and operation, and the degree to which this activation takes place depends on the hydration and circulation of the patient. The anaesthetic agent used is also important for the activation. Treatment with ACE-inhibitors blunts or abolishes the sympathetic response to anaesthesia/operation. ACEI treatment reduces the need for other hypotensive agents in controlled hypotensive anaesthesia. Some studies suggest that ACEI-treatment should be continued peroperatively on account of its stabilising effect on the circulation to avoid sudden fluctuations in blood pressure and organ perfusion. On the other hand measurements of the cerebral blood flow under anaesthesia in patients treated with ACEI have shown low values in a few patients and this led the authors to recommend discontinuation before anaesthesia. We conclude that controlled clinical trials to evaluate the haemodynamic and neurohumoral consequences of the interaction between ACEI and anaesthetics are required. PMID- 1311882 TI - Use of an inactivated infectious bursal disease oil emulsion vaccine in commercial layer chicks. AB - Commercial layer chicks of different ages were inoculated with either one-fifth, two-fifths or a full dose of an inactivated infectious bursal disease oil emulsion vaccine and then challenged with virulent virus. The partial doses given at seven or 10 days old gave only partial protection. A full dose given at 10, 14 or 28 days old failed to give full protection but a full dose administered at seven days old protected all the chicks after each challenge. PMID- 1311883 TI - Small cell carcinoma of the esophagus. Cytology and immunohistology in four cases. AB - Four cases of small cell carcinoma of the esophagus diagnosed by cytology, with subsequent histologic confirmation, were reviewed. The presence of small malignant cells in isolation with minimal cytoplasm was the common characteristic cytologic finding. Cellular molding was observed only focally in two cases, and streaking of nuclear material was not observed in any smear. The tumor cells were argyrophilic and not argentaffinic. Immunohistochemically the neoplastic cells were consistently immunoreactive with low-molecular-weight cytokeratins and epithelial membrane antigen. Esophageal washings as well as endoscopic biopsies yielded diagnostic material in all cases, but the histologic material was remarkable for crush artifacts that hindered the microscopic interpretation. PMID- 1311884 TI - Malignant fibrous histiocytoma of the esophagus. Report of a case with cytologic, immunohistologic and ultrastructural studies. AB - A 65-year-old man presented with an esophageal polyp that proved to be malignant pleomorphic fibrous histiocytoma, extremely rare at that location. Diagnosis of the abrasion cytology specimen was confirmed by immunohistochemical and electron microscopic methods. Differential diagnostic problems of pleomorphic soft tissue tumors and epithelial tumors mimicking them are discussed. PMID- 1311885 TI - Human papillomavirus DNA detection in Papanicolaou-stained cervical smears with a nonradioactive, in situ hybridization assay. AB - Archived Papanicolaou-stained cervical smears from women with different cervical pathologies were processed for human papillomavirus (HPV) DNA detection and typing with an in situ hybridization (ISH) assay that employed commercial biotinylated HPV DNA probes. Two HPV DNA probes were utilized: one included HPV genotypes 6/11 and the other, 16/18. The method yielded positive results for HPV DNA 6/11 in 5 cases with condylomata acuminata (100%) and in 2 of 47 with flat warty lesions (4.2%), whereas HPV DNA 16/18 was detected in 29/47 of the latter group (61.7%). In cases with cervical intraepithelial III or invasive squamous cell carcinoma the yield was lower: positive results for HPV DNA 16/18 were obtained in only one of the five cases with one or the other cervical pathology (20%). An analysis of the results showed that the sensitivity of the assay correlated with evidence in the Papanicolaou specimens of pathognomonic cell injury from HPV infection. In the presence of such cytologic features, HPV DNA typing was possible in 37/52 cases (65.4%). In view of the modest difficulty and relatively quick execution of the nonradioactive ISH assay, the authors believe that Papanicolaou cervical smears with cytologic changes of HPV infection could be processed by this method in order to acquire information on the HPV type or types involved in the cervical infection. PMID- 1311886 TI - Cytodiagnosis of classic lobular carcinoma and its variants. AB - The well-known cytologic features of lobular carcinoma traditionally consist of modest cellularity and small, atypical cells lying singly or in small groups. However, lobular carcinoma is a common pitfall in the cytodiagnosis of breast lesions. Knowledge of its varied histologic appearance can help to prevent diagnostic difficulties. Among 55 consecutive cases of breast needle aspirates with histologic follow-up, 9 lobular carcinomas were identified. The surgical material was examined for the following histologic variants: (1) classic, (2) solid, (3) alveolar, and (4) mixed; it was correlated with the cytologic findings. Pure, classic lesions were the most likely cause of false-negative diagnoses. Two of nine lobular carcinomas were diagnosed as benign due to scant cellularity and cell smallness. Four of nine were cytologically misclassified as ductal type due to more abundant cellularity and larger cells. This could be attributed to the predominant alveolar or solid patterns present in three cases. Only three of nine were accurately classified as lobular carcinoma, and all had a significant classic histologic element. Another important feature that is highly suggestive of lobular carcinoma is the presence of cytoplasmic vacuoles. They were overlooked in three of four cases. This study suggested that the traditional cytologic features of lobular carcinoma are present only in tumors with a predominantly classic histologic pattern. Awareness of the variant patterns and their cytologic features, including more abundant cellularity, larger cells and clusters, and cytoplasmic vacuoles, will aid in correct classification. PMID- 1311887 TI - Cystosarcoma phyllodes. Diagnosis by fine needle aspiration cytology. AB - The cytologic features of 10 benign, 2 borderline and 5 malignant phyllodes tumors were studied, and an attempt was made to correlate the cytologic findings with corresponding histologic categories. Seventy-five percent of the benign and borderline tumors were interpreted as benign cystosarcoma phyllodes on fine needle aspiration cytology. Eighty percent of the malignant phyllodes tumors were identified as malignant lesions cytologically. The cytologic features assessed were the epithelial:stromal ratio and morphology of the stromal component, including the degree of atypia, mitotic activity, capillary vessels traversing the stromal fragments, presence of foamy macrophages, histiocytic giant cells and bipolar naked nuclei. A diagnosis of phyllodes tumor was suggested cytologically by the presence of both epithelial and stromal elements; the stroma was present as cellular "phyllodes fragments" and isolated mesenchymal cells. The parameters suggesting malignancy were extreme paucity or absence of epithelial elements and stromal cells in diffuse sheets and clusters less cohesive than normal, with marked stromal atypia and mitotic activity. PMID- 1311889 TI - Fine needle aspiration cytology of phyllodes tumor. Potential diagnostic pitfalls. AB - We reviewed the fine needle aspiration cytologic findings in six cases of phyllodes tumor (PT). The average age of the patients at the time of the diagnosis was 47 years. Two cases were correctly diagnosed cytologically; both were malignant histologically. Of the histologically benign tumors, two were misdiagnosed as carcinoma, and a third was considered suspicious for carcinoma. The remaining case was diagnosed descriptively as "benign duct epithelium." Possible reasons for overdiagnosis include high cellularity of the smears, the presence of atypical ductal hyperplasia, paucity of the stromal component in the aspirates and occasional dissociation of epithelial cells. Recommendations are offered to prevent misdiagnosis. The cytologic differential diagnosis between fibroadenoma and PT is discussed briefly, and the considerable cytologic overlap that can occur is emphasized. The specific cytologic diagnosis of PT is not possible in many cases, but the presence of certain cytologic features in the correct clinical setting allows the diagnosis to be suggested. PMID- 1311888 TI - Aspiration biopsy smear pattern as a predictor of biologic behavior in adenocarcinoma of the breast. AB - Fine needle aspiration cytology (FNAC) is increasingly used for the initial diagnosis of breast carcinoma, yet few studies have investigated the prognostic importance of cytologic features seen in breast FNAC. We studied the relationship between prognosis and smear morphology in 26 patients with breast carcinoma for whom information from long-term follow-up was available. Specifically, we attempted to correlate nuclear grade and smear pattern with hormonal receptor status, lymph node status, breast recurrence and distant metastasis. In an additional five patients (on whom insufficient follow-up information was available), smear pattern and nuclear grade were correlated with hormonal status. Smears were classified into three patterns: typical (sheets and clusters), individual cell predominant and cluster predominant. The individual cell predominant pattern was associated with an increased incidence of distant metastasis when compared with the other two smear patterns (P less than .05). No statistically significant association was observed between smear pattern and the other factors studied. Nuclear grade 2 (of 3) was also associated with an increased incidence of distant metastasis. However, most grade 2 tumors (10/12) were of the individual cell predominant pattern. Smear pattern classification, along with DNA ploidy analysis and hormone receptor analysis of FNAC-derived material, may yield valuable prognostic information. PMID- 1311890 TI - Fungal fruiting heads in Papanicolaou smears as evidence of spatula contamination. PMID- 1311891 TI - Herpesvirus infection of the male urethra identified by cytology. PMID- 1311892 TI - The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children. AB - We have evaluated the effect of acute administration of atenolol, a selective beta-adrenergic antagonist, on the GH response to GHRH in nine obese children and in eight age-matched controls. The GH response to GHRH (1-29, 1 microgram/kg iv), evaluated both as the GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with atenolol (50 or 100 mg orally in subjects with body weight less than or greater than 40 kg, respectively, administered 120 min before the GHRH injection) significantly increased the GH response to GHRH in the obese subjects, such that their mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were similar to those of the control children after GHRH. Also in control children, atenolol caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were significantly higher in the controls than in the obese children given the same treatment. These data show that inhibition of central beta-adrenergic receptors counteracts the blunted GH response to GHRH present in the obese children. In view of the alleged mechanism of action of beta-adrenergic blockade (inhibition of endogenous SRIH release), our data suggest that the somatostatinergic system is intact in obesity, and that the suppressed GH secretion is due to other causes. PMID- 1311893 TI - Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage. AB - Gonadal function was evaluated in 23 men (aged 14.8-28.8 years) treated in childhood with cytotoxic drugs for a solid tumour. Group 1 (N = 14) had been treated with non-alkylating drugs only, while group 2 (N = 9) received the alkylating drug cyclophosphamide in addition (range 3.8-19.5 g/m2). Median age at the start of treatment was 4.6 years (range 0.6-16.1) in group 1 and 13.9 years (range 3.7-16.9) in group 2. Data of the patients were compared with a reference group consisting of 14 normal men. Almost all patients of both groups showed normal development of puberty; 13 of the 14 men in group 1 showed normal hormonal values. In group 2, basal LH and FSH as well as the LH and FSH responses to GnRH showed higher levels compared to those of a reference group (p less than 0.001). Correlation analysis showed an evident correlation between the total dose of received cyclophosphamide and the basal FSH level (r = 0.78; p = 0.002), the FSH response to GnRH (r = 0.73; p = 0.002) and the LH response to GnRH (r = 0.67; p = 0.002). There was no correlation between the hormonal parameters and the doses of the other cytotoxic drugs. Semen analysis showed azoospermia in four boys of group 2 and in none of group 1. Two patients in group 2 had an elevated FSH response to GnRH while their semen analysis was normal. CONCLUSIONS: (1) There is a dose-response relationship between the basal FSH, the LH and FSH responses to GnRH and the dose of cyclophosphamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311894 TI - Twenty-four year spironolactone therapy in an aged patient with aldosterone producing adenoma. AB - A case of primary aldosteronism treated with spironolactone therapy has been followed up for 24 years. This is probably the longest case of spironolactone therapy for primary aldosteronism that has ever been reported. Long-term treatment with spironolactone controlled the hypertension and prevented hypokalemic alkalosis in this patient, without any deleterious effects on steroid biosynthesis. Based on data obtained during dose reduction and subsequent withdrawal of spironolactone, it is suggested that the suppressed plasma renin activity associated with adenoma-induced aldosteronism develops prior to hypokalemia and hypertension. PMID- 1311895 TI - Cloning strategies for peptide hormone receptors. AB - With the advancement in molecular biology in the last decade many receptors have been cloned and the understanding of their mechanism of function has improved proportionally. In addition the concurrent discovery of receptor gene families has been used to design elegant cloning strategies which in turn have facilitated the characterization of new receptors and receptor subtypes. This review covers the most currently used cloning strategies and gives some examples. PMID- 1311896 TI - Positron emission and single photon emission computed tomographic studies in the frontal lobe with emphasis on the relationship to seizure foci. PMID- 1311897 TI - Cortical GABAergic control of epilepsy in photosensitive baboons. PMID- 1311898 TI - Recognizing malignant skin changes following breast cancer. AB - Estimates are that 180,000 cases of breast cancer will be diagnosed in 1992. Breast conservation therapy is becoming the treatment of choice for many women. Physicians providing long-term care for these women must be aware of the cutaneous presentations of local metastatic or recurrent disease, including inflammatory, nodular, telangiectatic and scirrhous variants. In addition, radiation changes, as well as the development of a secondary malignancy at the site of previous radiation therapy, must be distinguished from metastatic breast lesions. PMID- 1311899 TI - Differential recovery of cytomegalovirus from cellular and supernatant components of bronchoalveolar lavage specimens. AB - The recovery of cytomegalovirus from bronchoalveolar lavage (BAL) specimens was compared after inoculation of MRC-5 tube and shell vial cell cultures with four different BAL preparations. Analysis of culture results obtained with 55 cytomegalovirus culture-positive samples showed significant differences in the ability to isolate virus from the supernatant and cellular components of these specimens. There was a 52% reduction in cytomegalovirus recovery and a significant delay in the development of cytopathic effect in cultures inoculated with the cellular component of BAL specimens when compared to cultures inoculated with crude BAL cells and fluid. The mean time for detection of cytopathic effect was 11.8 days in tubes inoculated with crude BAL and 18.2 days for tubes inoculated with BAL cells. A similar effect was observed using a rapid shell vial culture technique. A 39% reduction in the number of isolates and a 57% reduction in the number of positive cells were observed in vials inoculated with cells when compared to cultures inoculated with crude BAL. By contrast, using cell-free BAL supernatant as inoculum did not reduce the number of positive cultures or delay development of cytopathic effect. The results suggest that in most BAL specimens, cytomegalovirus is associated with the cell-free, rather than the cellular, component. Although BAL cell concentrates frequently are used for cultivation of viruses from BAL, our results showed that the use of these preparations results in a significant number of false-negative cytomegalovirus cultures. PMID- 1311900 TI - Distribution of Lipiodol and evidence for tumor necrosis in hepatocellular carcinoma. AB - To study the distribution and thromboembolic effect of Ultrafluid Lipiodol, 15 surgically removed hepatocellular carcinomas with selective intraarterial Lipiodol injection 7 to 10 days before surgery and 15 noninjected controls were studied radiologically and histologically. Tissue blocks were processed with an en bloc silver impregnation technique for Lipiodol localization in histologic sections. Lipiodol was distributed evenly in tumors measuring less than 5 cm in diameter and peripherally in tumors measuring 10 cm or more. Lipiodol droplets were mainly extracellular. There was no difference in tumor architecture or in hemorrhage and necrosis scores between Lipiodol-injected cases and negative controls (1.18 versus 0.92). Similarly, in injected cases, no differences were observed between Lipiodol-positive and Lipiodol-negative areas (scores of x-ray Lipiodol-positive versus Lipiodol-negative areas: 1.17 versus 1.36; scores of microscopic Lipiodol-positive versus Lipiodol-negative areas: 1.18 versus 1.14). Lipiodol-negative but hypodense areas examined by x-ray proved to be necrosis or fibrosis with or without viable tumor islands. Lipiodol has no thromboembolic effects. The uneven Lipiodol distribution may account for its failure as a carrier for chemotherapeutic agents in large tumors. PMID- 1311901 TI - Hypopituitarism associated with a hypothalamic CMV infection in a patient with AIDS. PMID- 1311902 TI - Herpesvirus antibody levels in the etiologic diagnosis of the acute retinal necrosis syndrome. AB - Quantitative antibody levels to three herpesviruses in acute and chronic sera from six patients with clinical signs of the acute retinal necrosis syndrome were consistent with a specific etiologic diagnosis only in the two cases associated with cutaneous herpes zoster. Available data on acute and convalescent antibody titers to herpes group viruses from these six patients in addition to data from 27 acute retinal necrosis cases from the literature disclosed that only 13 of the 33 patients (39%) had a diagnostic increase or decrease in herpes group viral antibody levels on serial sampling. Three patients had nondiagnostic changes in viral antibody levels despite positive vitreous cultures for herpesviruses. In contrast, a review of 25 cases from the literature with paired antiviral serum and intraocular fluid antibody levels suggested a more promising approach to the etiologic diagnosis of the acute retinal necrosis syndrome. By calculating the ratio of antiviral antibodies in intraocular fluid and serum, an etiologic diagnosis could be made in 12 of 14 (86%) of subacute and convalescent samples. The sensitivity of this method decreased to 72% (13 of 18) when fluids were obtained earlier in the course of the disease. PMID- 1311903 TI - Repair of retinal detachment caused by cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. PMID- 1311904 TI - Coalition goal is elimination of TB. PMID- 1311905 TI - [Adenovirus infections in an emergency department]. AB - We have reviewed 108 emergency ward reports of patients with adenoviral positive cultures in "Doce de Octubre" Hospital in Madrid. Our aim was to know the most frequent symptoms of the infection so that identification and treatment could be managed more efficiently in our department. Cellular cultures were negative for other viruses such as CMV, enterovirus and herpesvirus. No bacteria were found in the throat cultures. Of the children who were evaluated, 78% were younger than 3 years old. The most frequent symptom was high fever with an otherwise good state of health. During the physical examination, a reddened throat with an exudate was found in half of the patients. A white blood cell count of over 15,000 was found in 33% of the patients with a left shift in 20%. The clinical findings overlapped with throat bacterial infections in 66%, lower respiratory infections in 14%, and more unusual, gastroenteritis, hematuria, intestinal invagination or exanthemas. Only 15% were not given antibiotic therapy. PMID- 1311906 TI - [Serology in infectious mononucleosis in children]. AB - 28 pediatric patients with signs and symptoms of infections mononucleosis (MI) are presented. We did a serologic study in all of them from two or three serum specimen collected in 2-3 week intervals. We detected IgG VCA but no antibodies against T. gondii or CMV in all of them. The level of the titers of these antibodies didn't help in the establishment of the phase of the illness. IgM VCA was present in the serum of 22 patients, with or without heterophil antibodies (AH), Meanwhile the remaining 6 patients had no antibodies to IgM VCA or AH. In all serum samples we evaluated the ratio of IgM/IgG EBNA. In patients with primary infection of MI, this value was greater than 1 or equal to 1, meanwhile it was less than 1 in recent or past infections. PMID- 1311907 TI - Why was treatment of cytomegalovirus retinitis randomized? PMID- 1311908 TI - Metastatic tumor presenting as chronic otitis and facial paralysis. PMID- 1311909 TI - Cytochrome c oxidase deficiency and long-chain acyl coenzyme A dehydrogenase deficiency with Leigh's subacute necrotizing encephalomyelopathy. AB - A female infant was seen at the age of 2 months because of hypotonia, delayed motor development, and lactic acidosis, and she died at age 13 months due to respiratory failure. In a muscle specimen taken at 11 months and in a liver specimen obtained 1.5 hours postmortem, we found decreased activities of cytochrome c oxidase and long-chain acyl coenzyme A dehydrogenase. Neuropathological changes were typical for Leigh's subacute necrotizing encephalomyelopathy. To our knowledge, this is the first report of a combined defect of complex IV of the respiratory chain and of the long-chain specific acyl coenzyme A dehydrogenase of beta-oxidation in muscle and liver. PMID- 1311910 TI - Relapsing and remitting human immunodeficiency virus-associated leukoencephalomyelopathy. AB - We describe a 33-year-old homosexual man with a steroid-responsive, remitting and relapsing leukoencephalopathy associated with recent human immunodeficiency virus type 1 (HIV-1) seroconversion. Biopsy of a parieto-occipital lesion revealed demyelination and astrogliosis with focal necrosis. Detailed investigations demonstrated no pathogens in the brain other than HIV-1. This patient illustrates that a neurological disorder clinically indistinguishable from multiple sclerosis may be the presenting manifestation of HIV-1 infection and may occur in the absence of clinically significant immunosuppression. PMID- 1311911 TI - Lethal cytomegalovirus infection in preterm infants: clinical, radiological, and neuropathological findings. AB - Fifteen premature infants with lethal congenital cytomegalovirus infection were studied to determine the clinical, neuroradiological, and neuropathological characteristics of the disease in this population. Nine infants were liveborn but died at a postnatal age of 18 +/- 21 days; 6 infants were stillborn. Clinical findings in liveborn infants included microcephaly (77%), seizures (55%), hypotonia (33%), and multiple contractures (18%). Ophthalmological findings included chorioretinitis, optic atrophy, and corneal opacities. Neuroradiological findings included the postnatal evolution of periventricular calcification in 1 infant, and cerebellar hypoplasia diagnosed by magnetic resonance imaging in 1 infant. Neuropathological findings included periventricular necrosis and calcification (12), associated diffuse calcification frequently involving the convexity of the gyri (6), cerebellar hypoplasia (5), periventricular leukomalacia (2), intraventricular hemorrhage (2), hydrocephalus (2), and porencephalic cyst (1). Intranuclear inclusion bodies within the brain were observed in 4 infants, whereas systemic inclusion bodies were present in all infants. These data indicate several atypical findings in preterm infants rarely reported in term infants, including hypotonia, multiple contractures, periventricular leukomalacia, and optic atrophy. PMID- 1311912 TI - [Transarterial "pile-up" infusion therapy of cisplatin and lipiodol emulsion in hepatic malignancies without TAE (transcatheter arterial embolization)]. AB - We developed a modified transcatheter arterial infusion method using anticancer agents to treat hepatic malignancies; intermittent injections of iodized oil, lipiodol, containing adriamycin or epirubicin during the arterial infusion of cisplatin (75-200 mg/body) in order to achieve a higher concentration and longer retention of these anticancer agents in the tumor tissue. Fourteen patients with hepatocellular carcinoma (HCC) and five patients with metastatic liver cancer were treated with this "pile-up" arterial infusion therapy by anticancer agents without gelatin sponge TAE. In HCC patients, 50% or greater reduction in tumor size was obtained in 7 of 14 patients (50%). Serum AFP levels decreased by more than 75% in 6 of 7 patients in whom pretreatment serum levels of AFP were more than 200 ng/ml. The one-year and two-year survival rates were estimated at 55% and 27.5%, respectively, by the Kaplan-Meier method. Significant reduction in tumor size was not observed in 5 cases with metastatic liver cancer. Concerning the adverse effects, alimentary symptoms and fever were noted for a few days in many cases, but they were temporary and tolerable in almost all of the patients. Severe adverse changes in laboratory data were not observed. Thus this "pile-up" infusion therapy of anticancer agents without TAE may be a useful therapy for HCC. PMID- 1311913 TI - [Transcatheter arterial infusion of adriamycin-lipiodol suspension to patients with metastatic liver tumor]. AB - Adriamycin-Lipiodol suspension was administered to 44 patients with metastatic liver tumor using the transcatheter arterial infusion method. The result revealed 23% in the over all effect (partial response or more) of the therapy which was evaluated by comparing the CT images of the tumor, 47% in the 25% or more of the decrease of the tumor, and 65%, very effective in the decrease of the smaller tumor (less than 50 cm2). Except for a case of hepatic subcapsular hematoma after the infusion of Adriamycin-Lipiodol suspension, minor complications were experienced such as abdominal pain, slight fever, and so on. No serious exacerbation in liver function test and white blood cell count was noted. PMID- 1311914 TI - [Effect of lipiodol-cisplatinum arterial infusion chemotherapy on cellular immunity]. AB - A Lipiodol-cisplatinum suspension (LPD/CDDP) was applied by intrahepatic arterial infusion chemotherapy to treat 15 cases of inoperable hepatoma. Pre- and post application changes in leucocytes, monocytes, platelets and lymphocytes in patients were examined. Natural killer activity was determined and analysis by two-color method was performed. After infusion chemotherapy, leucocytosis and monocytosis were quite conspicuous. NK activity was reduced after application of LPD/CDDP, but this effect may have been partly due to the influence of methylprednisolone. Cellular immunity was not influenced by LPD/CDDP infusion without low reduction of NK activity. PMID- 1311915 TI - [A case with hepatocellular carcinoma effectively treated by continuous hepatic arterial infusion of etoposide, epirubicin and CDDP]. AB - A 53-year-old man who suffered from advanced hepatocellular carcinoma (HCC) was treated with hepatic arterial infusion (HAI) of Etoposide, Epirubicin and CDDP. Treatment consisted of a continuous HAI of Epirubicin (50 mg/body, day 1.7), CDDP (75 mg/body, day 2.8) and Etoposide (80 mg/body, day 4-6). He had two series of infusions and was treated by transarterial embolization using CDDP powder (100 mg) added to lipiodol and aluminum stearate as suspension following HAI. The tumor regression rate was about 60% after HAI, but the remaining tumor seemed to be almost necrotic. AFP and PIVKA-II reached the normal range after TAE. We could not find lipiodol accumulated in tumor on CT carried out eight weeks after TAE. No recurrence has been noticed in the following 8 months. Toxicity was not so severe and was well tolerated. PMID- 1311917 TI - Intraoperative monitoring of an unusual brachial plexus tumor. AB - This case illustrates the importance of intraoperative monitoring of neuronal function to help separate tumor tissue from neural tissue in a 54-year-old patient with left shoulder pain resulting from a desmoid tumor. Preoperative nerve conduction and electromyographic studies showed a lesion in the lateral cord of the brachial plexus, which was found to be intimately involved with the tumor mass and was splayed into a very thin effaced sheet of neural tissue. Stimulation of the tumor/nerve tissue mass proximal to the lesion was impossible due to the invasion of the brachial plexus by the tumor. The technique that was adapted for this unusual presentation was to stimulate the tumor/nerve tissue mass itself and record compound muscle action potentials distally. With the technique described, a subtotal resection of an aggressive fibromatosis enmeshed in the proximal brachial plexus was possible, and excellent relief of pain symptoms and retention of functional capabilities of the involved extremity were achieved. PMID- 1311916 TI - Growth patterns after surgery for virilising adrenocortical adenoma. AB - Analysis of growth in nine girls after successful surgical removal of a virilising adrenocortical adenoma showed that five girls continued to grow rapidly for up to 18 months after operation and subsequently had normal growth velocities. The other four girls grew at normal rates after surgery. Only one girl showed progressive advance in bone age after operation and she subsequently had precocious puberty. PMID- 1311918 TI - Hydroxyapatite orbital implant after enucleation. Experience with initial 100 consecutive cases. AB - The hydroxyapatite orbital implant is designed to provide the enucleated patient with improved motility of the prosthesis. We report the results of our first 100 consecutive cases of hydroxyapatite implantation in eyes enucleated primarily for intraocular neoplasms. During a median of 11 months' follow-up, there have been no cases of orbital infection, implant extrusion, or implant migration. Minor postoperative problems have included transient orbital pain in six patients, Tenon's fascia edema and buried peg from tissue overgrowth in two patients each, wound erosion and peg extrusion in one patient each, and audible click of the peg in three patients. Movement of the socket and fornices was excellent in 99% of patients. Motility was cosmetically satisfactory with 10 degrees to 15 degrees rapid darting prosthesis movement present in 96% of patients regardless of whether the peg had been placed. Large-degree prosthesis motility (greater than 15 degrees) was present in 24% of all patients and was most impressive in those adults who had the peg in place and in children. The hydroxyapatite implant appears to be well tolerated and provides prosthesis motility with few problems. PMID- 1311919 TI - Demonstration of receptors for epidermal growth factor on cultured rabbit chondrocytes and regulation of their expression by various growth and differentiation factors. AB - Epidermal growth factor (EGF) receptors were demonstrated on cultured rabbit costal chondrocytes. After crosslinking, the receptors on the cells with 125I EGF, one major band of 170 KDa was separated by SDS-PAGE. Scatchard analysis demonstrated two classes of EGF receptors with Kd values of 0.3 nM and 1.6 nM. The numbers of high and low affinity receptors were 3,000 and 10,000 per cell, respectively. EGF receptors on chondrocytes were increased by treatment with retinoic acid and interleukin-1 beta, which inhibited proteoglycan synthesis. On the other hand, parathyroid hormone and dibutyryl cyclic AMP, which stimulated proteoglycan synthesis, decreased the number of EGF receptors. Treatments with these agents did not change the affinity of the receptors. These findings suggest that the number of EGF receptors is a negative marker of chondrocyte differentiation. PMID- 1311920 TI - Calcium is required for the mitogenic activation of lymphocytes by periodic acid oxidation. AB - This investigation of Ca2+ requirements for the mitogenic activation of lymphocytes by periodic acid has shown that oxidation by periodate causes an immediate and transient increase of Ca2+ influx and efflux in oxidized cells. Oxidized lymphocytes maintained in the medium containing 0.2 mM Ca2+ failed to proliferate or to produce IL-2, whereas a 1.4 mM Ca2+ concentration was shown to be sufficient to sustain cellular proliferation and IL-2 secretion. These results indicate that mitogenic activation of lymphocytes by periodic acid oxidation is Ca(2+)-dependent. PMID- 1311921 TI - The unique N-terminal sequence of testis angiotensin-converting enzyme is heavily O-glycosylated and unessential for activity or stability. AB - The testis-specific isozyme of angiotensin-converting enzyme (ACE) is identical, from residue 68 to the C terminus, to the second half or C-terminal domain of somatic ACE. However, the first 67 residues, comprising the signal peptide and a Ser-/Thr-rich 36-residue sequence that constitutes the N terminus of mature testis ACE, are unique. We have expressed a mutant human testis ACE lacking this 36-residue N-terminal sequence and find that compared to the wild-type protein the mutant is 15 kDa smaller due to the loss of greater than 90% of all O-linked sugars, but that it retains full enzymatic activity and is stable in culture. Heavy O-glycosylation is a property of testis ACE that is not shared by the somatic enzyme and is attributable to this unique sequence. PMID- 1311922 TI - Creation of amyloid fibrils from mutant Asn187 gelsolin peptides. AB - The amyloid protein in familial amyloidosis, Finnish type, is a 71 amino acid long fragment of the inner region of mutant Asp187----Asn gelsolin. The mechanism of gelsolin amyloid formation was tested with synthetic 11 and 30 residue peptides corresponding to the normal and mutant sequence of gelsolin. Fibrils meeting the morphologic criteria of amyloid were formed from the mutant Asn187 peptides. Substitution of the normal Asp187 residue with the mutant Asn residue resulted in a 9-fold increase in fibrillogenicity as determined by quantitative fluorometry. The present study demonstrates the first successful in vitro creation of amyloid-like fibrils from Asn187 gelsolin peptides and provides evidence that amyloid formation in Finnish amyloidosis is a direct consequence of the Asp187----Asn substitution in gelsolin. PMID- 1311923 TI - Total synthesis of horse heart cytochrome C. AB - A strategy based on complexation-assisted condensation of large synthetic protein fragments and mitochondria-mediated stereospecific heme insertion has been utilized to assemble a functional molecule corresponding to native horse heart holocytochrome c. This original approach offers the unique opportunity of selective modifications both in the C-terminal and in the N-terminal regions of the apoprotein and may represent an useful alternative to site-directed mutagenesis, particularly when D-amino acids, chemically and/or isotopically modified or other unnatural amino acids have to be introduced in this important molecule. The present result is an example of how solid phase peptide synthesis of large protein fragments in conjunction with the availability of a specific recognition process may extend the potentiality of the chemical approach to the synthesis of an entire protein. PMID- 1311924 TI - Cloning and increased expression of an insulin receptor substrate-1-like gene in human hepatocellular carcinoma. AB - Human insulin receptor substrate-1 (hIRS-1) cDNAs were cloned from a lambda GT11 expression library using a monoclonal antibody (MAb) produced against a human hepatocellular carcinoma (HCC) cell line (FOCUS). The predicted amino acid sequence derived from both a genomic DNA fragment and the cDNAs showed a 90.5% identity to the previously reported rat IRS-1 cDNA [Sun, X.P. (1991) Nature 352, 73-77]. Multiple potential phosphorylation sites, that suggest an intrinsic function of this molecule in response to insulin action, were highly conserved between the two species. A c.a. 180 kDa hIRS-1 protein was immunoprecipitated and found to be phosphorylated on tyrosine residue(s) following insulin stimulation of HuH-7 HCC cells. Northern blot analysis demonstrated a single c.a. 5 kb transcript in HCC cell lines and tissues. Higher levels of hIRS-1 gene transcripts were observed in HCC tumors compared to adjacent non-involved normal liver. PMID- 1311925 TI - PAF-induced activation of polyphosphoinositide-hydrolyzing phospholipase C in cerebral cortex. AB - The action of platelet-activating factor (PAF) on phosphoinositide hydrolysis was studied in rat brain slices. PAF produced a significant increase of 32P incorporation into phosphoinositides and phosphatidic acid (PA), in a dose- and time-dependent manner. Concomitantly, an increase of inositol phosphates and diacylglycerol (DAG) production was observed. Both inositol bisphosphate (IP2) and inositol trisphosphate (IP3) were detected as early as 5 s and they returned immediately to basal levels; concomitantly, formation of inositol monophosphate (IP) was detected. These findings demonstrated that PAF causes a rapid hydrolysis of polyphosphoinositides in cerebral cortex by a phospholipase C-dependent mechanism followed by subsequent resynthesis. PMID- 1311926 TI - A new type of hepatitis C virus in patients in Thailand. AB - Partial nucleotide sequences in the tentative NS5 region of the hepatitis C viral genome obtained from patients with chronic hepatitis in Thailand were analyzed by reverse transcription followed by the polymerase chain reaction. Of ten samples studied, four showed low homologies to any known type of HCV: the homologies of the nucleotide sequences of these clones with HCV-J, -US, -K2a and -K2b were 66.5 69.1%, 66.5-68.2%, 61.2-64.1% and 64.4-66.2%, respectively, and the homologies of their deduced amino acids sequences were 71.7-75.2%, 71.7-75.2%, 69.0-72.6% and 69.9-73.5%, respectively. These four clones were classified a new distinct type of HCV, named HCV-T. Moreover, the nucleotide and amino acid sequence homologies of the four HCV-T clones showed that the HCV-T type could be classified into two genotypes, HCV-Ta and HCV-Tb. PMID- 1311927 TI - Expression of the heparin-binding growth factor receptor genes in human megakaryocytic leukemia cells. AB - K-sam/bek, N-sam/flg and FGFR3/sam3 establish gene family of the receptors for heparin-binding growth factors (HBGFs) or FGFs. These mRNAs were detected in human leukemia cells, CMK, K562 and HEL, which have megakaryocytic phenotype or the potency to differentiate into megakaryocytic lineage. In CMK cells N-sam/flg transcript level was enhanced by the culture with 12-O-tetradecanoylphorbol-13 acetate (TPA). cDNA-polymerase chain reaction identified K-sam/bek mRNA in human platelets, suggesting the involvement of HBGFs in megakaryocytopoiesis and functions of platelets. PMID- 1311928 TI - [Malignant fibrous histiocytoma in the area of the head and neck]. AB - Although malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult life, it is fairly rare in the head and neck region (3-6%). Between 1983 and 1991 8 patients with MFH in the head and neck region have been observed and treated at the ENT-department of the University of Tubingen. 5 patients have been operated (laryngopharyngeal localization), 2 patients underwent irradiation (unresectable fast growing T4-tumors of the pharynx and thyroid) and one female patient refused further therapy after two resections elsewhere. Operated patients showed no evidence of disease 2-8 years after resection (all margins have been controlled histologically). Both irradiated patients died 4 respectively 2 months after full (70 Gy) and incomplete (17 Gy) radiotherapy without visible positive effects. Both patients developed pulmonary metastasis. Since MFH can grow in thin layers along musculaoponeurotic structures the exact size is not always demonstrable by ultrasound, CT or MR scans. Metastasis occur in up to 40%, preferentially in regionary lymph nodes, in lung, liver and skeletal system. These phenomenon requires a full pretherapeutic staging. Histologically MFH is sometimes hard to distinguish from other tumors as for example various sarcomas and pleomorphic carcinoma. Therefore, immunohistochemical (mesenchymal markers) and electron microscopical investigations are advised. Resection with exact histological controll of all margins is the therapy of choice. We experienced that laryngeal MFH (n = 3) can be resected without laryngectomy under certain circumstances. Although unsuccessfull in our two cases, according to the literature, radiotherapy should be administered in unresectable cases. Depending on localization and size of MFH long survival, in single cases healing, of this disease is possible by surgical treatment. PMID- 1311929 TI - Enhanced RNase H activity with methylphosphonodiester/phosphodiester chimeric antisense oligodeoxynucleotides. AB - Chimeric oligodeoxynucleotides, comprised of internal phosphodiester and terminal methylphosphonodiester sections, possess many beneficial characteristics as antisense effectors. We have investigated the effects of progressive replacement of phosphodiester by methylphosphonodiester linkages on hybrid stability with complementary RNA and DNA. The melting temperatures (Tms) of oligodeoxynucleotide/RNA heteroduplexes were found to decrease dramatically with increasing methylphosphonate substitution. In contrast, a smaller reduction in Tm was observed for comparable DNA heteroduplexes. This disparate reduction in hybrid stability was found with both the G + C-rich human c-myc and A + T-rich human c-Ha-ras sequences used, suggesting that methylphosphonate oligodeoxynucleotide analogues generally hybridize with less affinity to RNA than DNA. RNase H assays were employed to determine if the noted decreases in Tm impaired the ability of chimeric oligodeoxynucleotides to direct the degradation of RNA. Contrary to expectation, increasing methylphosphonate substitution gave rise to increasing rates of RNA degradation for both the c-myc and c-Ha-ras series. The present results suggest that chimeric oligodeoxynucleotide analogues may be of considerable utility as antisense agents in systems where RNase H is thought to make a major contribution to inhibition of gene expression. PMID- 1311930 TI - Production and characterization of recombinant insulin-like growth factor-I (IGF I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. AB - The development of an efficient expression system for insulin-like growth factor I (IGF-I) in Escherichia coli as a fusion protein is described. The fusion protein consists of an N-terminal extension made up of the first 46 amino acids of methionyl porcine GH ([Met1]-pGH) followed by the dipeptide Val-Asn. The latter two residues provide a unique hydroxylamine-sensitive link between [Met1] pGH(1-46) and the N-terminal Gly of IGF-I. Downstream processing of the fusion proteins involved isolation of inclusion bodies, cleavage at the Asn-Gly bond, refolding of the reduced IGF-I peptide and purification to homogeneity. This expression system was also used to produce two variants of IGF-I in which Glu3 was substituted by either Gly or Arg to give [Gly3]-IGF-I and [Arg3]-IGF-I respectively. Production of milligram quantities of IGF-I peptide was readily achieved. The purity of the IGF-I, [Gly3]-IGF-I and [Arg3]-IGF-I was established by high-performance liquid chromatography and N-terminal sequence analysis. [Gly3]-IGF-I and [Arg3]-IGF-I were more potent than IGF-I in biological assays measuring stimulation of protein synthesis and DNA synthesis or inhibition of protein breakdown in rat L6 myoblasts. Both analogues bound very poorly to bovine IGF-binding protein-2 and slightly less well than IGF-I to the type-1 receptor on rat L6 myoblasts. We conclude that reduced binding to IGF-binding proteins rather than increased receptor binding is the likely explanation for the greater biological potency of the analogues compared with IGF-I. PMID- 1311931 TI - A single amino acid residue replacement in the beta subunit of human chorionic gonadotrophin results in the loss of biological activity. AB - The heterodimer, human chorionic gonadotrophin (hCG), contains an alpha subunit that is common to the glycoprotein hormones and a hormone-specific beta subunit. A comparison of all known beta amino acid sequences shows that an aspartic acid at position 99 (with the numbering scheme for hCG-beta) is one of the seven non Cys invariant residues. Using site-directed mutagenesis we have replaced hCG-beta Asp99 with Arg. Chinese hamster ovary cells, containing a stably integrated gene for bovine alpha subunit, were transiently transfected with plasmids containing wild-type and mutant hCG-beta cDNAs. The Arg99 beta mutant associated with the alpha subunit, but the resulting heterodimer failed to enhance intracellular cyclic AMP production in a gonadotrophin-responsive transformed murine Leydig cell line. Thus, a single amino acid residue replacement in this glycosylated heterodimer containing 237 amino acid residues is sufficient to abolish activity. PMID- 1311932 TI - Transformed rat tracheal epithelial cells exhibit alterations in transforming growth factor-beta secretion and responsiveness. AB - The purpose of our studies was to define abnormalities in the transforming growth factor-beta (TGF-beta) system of transformed rat tracheal epithelial (RTE) cells that might cause their abnormal growth behavior. We found that many, but not all, of the transformed cell lines were hyporesponsive or unresponsive to the growth inhibitory effects of TGF-beta 1. Scatchard and receptor cross-linking analyses indicated that loss of TGF-beta 1 responsiveness of transformed cells was probably not due to changes in receptor number or affinity, or to changes in expression of the three TGF-beta-binding protein subtypes. Transformed cells were found to secrete far less TGF-beta-like activity (less than 1/10) than primary cells. Cultured normal and transformed RTE cells expressed three TGF-beta 1 transcripts of 2.5, 1.9, and 1.4 kb. In contrast, rat kidney tissue, a rat embryo fibroblast cell line, and a rat liver cell line expressed only the typical 2.5-kb mRNA transcript commonly reported in the literature. In spite of the marked differences in TGF-beta secretion between normal and transformed cells, their levels of TGF-beta 1 mRNA expression were similar. This suggests a change in the posttranscriptional regulation of TGF-beta 1 expression. TGF-beta 2 message was not detected in either normal or transformed RTE cells in culture. These findings are consistent with the hypothesis that the abnormal growth behavior of transformed RTE cells is at least in part due to disturbances of the TGF-beta system. PMID- 1311933 TI - Cytoreductive therapy of multidrug-resistant hepatocellular carcinoma: negative regulation of growth using combination differentiation therapy. AB - In vitro studies of the mouse erythroleukemia cell system have identified at least 300 agents capable of inducing differentiation by mechanisms that remain to be elucidated. We have recently begun to examine recombinant cytokines as possible agents in inducing differentiation of tumor cells, specifically, malignant cells resistant to cytotoxic drugs. One such cytokine, transforming growth factor-beta (TGF-B1), is a multifunctional peptide that exists in at least five different isoforms in vertebrate species. Recently, there has been a great deal of interest in the role of TGF-B1 as an important multifunctional growth regulator that induces cells of mesenchymal origin to divide while inhibiting the growth of nontransformed epithelial cells. In this study, we combined the effects of the differentiation agent hexamethylene bisacetamide and the inhibiting effects of TGF-B1 on a multidrug-resistant human liver hepatocellular carcinoma and demonstrated the synergistic interaction of these two agents; this synergy resulted in a cell death rate of 80%. These data support the concept of programmed cell death and suggest that drug-resistant tumor cells may be susceptible to the combination of cytokines and differentiating agents. PMID- 1311934 TI - HIV seropositivity in community-recruited and drug treatment samples of injecting drug users. AB - OBJECTIVE: To assess the representativeness of drug use treatment samples for measuring HIV seroprevalence among injecting drug users (IDU) in community settings. DESIGN: Seroprevalence was determined in two cross-sectional, convenience samples including an unlinked survey of IDU entrants to all publicly funded drug-treatment programs and a survey of community-recruited IDU. METHODS: Unconditional logistic regression [odds ratio (OR)] was used to calculate unadjusted and adjusted OR to measure the association between HIV seropositivity and site of recruitment. RESULTS: Between 1988 and 1989, 25% of 870 community recruited IDU were seropositive, compared with 13% of 671 entrants to drug treatment programs. This twofold risk of HIV seropositivity among community recruited IDU remained after adjustment for sample differences in gender, race ethnicity, and age group (adjusted OR, 2.09; 95% confidence interval, 1.58-2.78). CONCLUSIONS: These results suggest the importance of extending HIV surveillance outside of drug-treatment facilities. Active serologic surveillance may be feasible by coupling recent saliva and fingerstick sampling techniques with existing community outreach education efforts. PMID- 1311935 TI - Dronabinol effects on weight in patients with HIV infection. PMID- 1311936 TI - Statistics from the Centers for Disease Control. PMID- 1311937 TI - Inactivation of Ca current during the action potential in guinea-pig ventricular myocytes. AB - The inactivation of Ca channels during the action potential plateau of guinea-pig ventricular myocytes was investigated by interrupting action potentials with voltage clamp pulses to assess Ca channel availability. The influence of the bulk cytosolic calcium [( Ca]i) transient on Ca channel inactivation was also studied by impaling cells with microelectrodes containing the Ca chelator BAPTA (1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 125-200 mM). Ca channel availability decreased progressively with action potential duration, reaching approximately 20% of maximum availability after 100 ms and falling close to zero at the end of the plateau. When membrane potential became more negative than -40 mV Ca channel availability increased. Elevation of the action potential plateau to more positive levels increased Ca channel availability (even though this was expected to increase peak [Ca]i). When the cytosol was loaded with BAPTA Ca channel availability during the plateau increased. Inactivation of Ca channels was not, however, abolished. The observations are consistent with the hypothesis that in guinea-pig ventricular myocytes the majority of Ca channels are inactivated during the plateau and recovery does not occur until repolarization is almost complete. It may be that while the cytosolic Ca transient (that is generated in part by release of Ca from the intracellular Ca stores) modulates Ca channel availability, significant inactivation of the Ca channel during the action potential plateau is due to voltage dependent inactivation and to Ca induced inactivation resulting from the Ca which enters the myocyte via Ca channels. PMID- 1311938 TI - Intracellular pH changes induced by hypoxia and anoxia in isolated sheep heart Purkinje fibres. AB - The effects were studied of hypoxia on intracellular ion activities in sheep heart Purkinje fibres. The intracellular pH (pHi), surface pH (pHs), intracellular potassium activity (aki), and intracellular sodium activity (aNai) of the cells were recorded using liquid ion exchanger-filled microelectrodes. Various methods of inhibiting oxidative phosphorylation were compared for their effect on pHi. These methods were the use of hypoxia, anoxia or NaCN (2 mM). Hypoxia was produced by degassing solutions under reduced pressure then bubbling with 100% nitrogen gas. Anoxia was produced in a similar manner but with the addition of the reducing agent sodium dithionite (0.5 mM) to remove all traces of oxygen from the solutions. Anoxia caused the most marked changes. Concentration of sodium dithionite between 0.1 and 1 mM produced similar maximum rates of acidification. High concentrations (5 or 20 mM) could produce larger intracellular acidifications apparently unrelated to anoxia. The effects of hypoxia and NaCN were similar. Inhibition of Na(+)-H+ exchange with amiloride (1 mM) had little effect on the pH changes produced by hypoxia. Periods of hypoxia exceeding 1 h still resulted in rapid, readily reversible changes in pHi. Hypoxia caused a rise in aNai, the effect being larger in anoxic conditions. The intracellular K+ activity decreased in hypoxia with further decreases in anoxic conditions. The intracellular ion changes produced during hypoxia are discussed in terms of the production of lactic acid by the cells and changes in the ATP supply to the Na(+)-K+ pump. PMID- 1311939 TI - Calcium oscillations in single isolated human vascular smooth muscle cells. AB - When cultured human vascular smooth muscle cells are exposed to sodium-free solutions oscillations in intracellular calcium concentration are observed. In some cells the oscillations are maintained at constant amplitude throughout the exposure to Na(+)-free solution, in others the amplitude of the oscillations falls to a lower, steady-state level. The oscillations are also activated and maintained in isotonic, Na(+)-free, K+ solutions suggesting that the underlying mechanism does not involve the opening and closing of voltage-dependent channels. The possible mechanisms responsible for this behaviour are discussed. PMID- 1311940 TI - 'Multifocal hairy leukoplakia'. PMID- 1311941 TI - HIV-related risk behaviors among cocaine users. AB - Risk behaviors related to human immunodeficiency virus (HIV) infection and transmission were studied in a sample of 167 male cocaine users admitted during a 5-month period to an inpatient drug treatment program. Data obtained included drug history and related behaviors, sexual behaviors, knowledge, and attitudes regarding HIV infection and AIDS. Approximately 20% of the sample had used IV drugs in the year prior to the interview and 94% of these reported sharing needles; 20% of the IV drug users (IVDUs) reported always using bleach to clean needles. With regard to sexual practices, 7% of the total sample reported sex with other males in the year prior to the interview; 86% of the total sample reported having sex with females and 80% of these noted they never or rarely used condoms during vaginal sex. Respondents generally did not believe they themselves were at high risk for HIV infection, yet they continued to engage in acknowledged high-risk behaviors. These findings suggest that IVDUs and non-IV cocaine users are likely to contribute to the spread of HIV in several populations. PMID- 1311942 TI - Decreased plasma superoxide scavenging activity in immunological disorders- carboxyethylgermanium sesquioxide (Ge-132) as a promoter of prednisolone. AB - We investigated so-called superoxide scavenging activity (SSA) of plasma in patients with several immunological disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyo-dermatomyositis (PM), progressive systemic sclerosis (PSS), myasthenia gravis (MG) and autoimmune thyroid disease (AT), using the electron paramagnetic resonance/spin trapping technique. Since carboxyethylgermanium sesquioxide, Ge-132, has been reported to modulate both the immune response and leukocyte functions, we have studied in vivo effect of Ge-132 on plasma SSA and other laboratory parameters in these disorders. The plasma SSA was significantly lower in RA, SLE, PM and PSS, but not in MG and AT, as compared with that in healthy controls. An inverse correlation was observed between plasma SSA and parameters such as erythrocytes sedimentation rates, absolute number of leukocytes, C-reactive protein and serum globulin levels. Furthermore, plasma SSA was significantly decreased in rheumatoid factor-positive patients as compared to negative patients. No correlation was observed between plasma SSA and factors such as ages, sex of patients or the other laboratory parameters, such as serum albumin, triglyceride, cholesterol, hemoglobin and serum iron levels. Patients treated with prednisolone, especially ones with RA, showed an increase of plasma SSA. It appears that Ge-132 promotes prednisolone effects. Our results indicate that a decrease in plasma SSA is not disease specific, but inversely correlates with the severity and activity of inflammation. The methodology to measure plasma SSA presented in this work provides a helpful tool for determining the actual activity of the diseases as well as in vivo studies of antiinflammatory agents. PMID- 1311943 TI - Azoles, allylamines and drug metabolism. AB - Four antifungal drugs, the azoles ketoconazole, itraconazole and fluconazole, and the allylamine terbinafine, were studied for their effects on the metabolism of cyclosporin A (CyA) and cortisol by human liver microsomes in vitro (n = 3). Ketoconazole produced marked inhibition of CyA hydroxylase (to metabolites M17 and M1) with IC50 and Ki values of 0.24 +/- 0.01 and 0.022 +/- 0.004 microM, respectively. On the basis of the IC50, itraconazole was 10 times less potent (IC50 of 2.2 +/- 0.2 microM), and fluconazole and terbinafine were each above 100 microM. No kinetic parameters were calculated for terbinafine because of the lack of inhibitory effects. Ketoconazole was the most potent inhibitor of cortisol metabolism (to 6 beta-hydroxycortisol, IC50 = 0.6 microM). Itraconazole produced marked inhibition of cortisol metabolism (IC50 = 2.4 microM), but fluconazole and terbinafine had little effect. These data confirm that ketoconazole is a potent inhibitor of cytochrome P-450-IIIA4, and this has clinical relevance. Although the inhibition with fluconazole was much less than with itraconazole at equimolar concentrations, it should be noted that in-vivo plasma concentrations of fluconazole are much greater than that of itraconazole. Clinical interactions of CyA with both fluconazole and itraconazole have been reported; in contrast to these azoles, terbinafine does not have the same interaction potential. PMID- 1311944 TI - Clinical significance of interactions with antifungal agents. AB - Antifungal drugs act by a variety of mechanisms. Agents such as substituent imidazoles and triazoles, which act by inhibiting the fungal cytochrome P-450 dependent enzyme lanosterol N-demethylase, have the potential to inhibit host cytochrome P-450-dependent drug metabolism. This is discussed with respect to ketoconazole, fluconazole and itraconazole. In contrast, allylamines, which have a different mode of action and a weaker ability to bind to cytochrome P-450, are not expected to inhibit clinical drug oxidation. Inducers of drug metabolism, especially rifampicin, phenobarbitone and phenytoin, may lower plasma (and tissue) concentrations of those antifungals metabolized by mixed function oxidases, with therapeutic consequences. PMID- 1311945 TI - The protein C anticoagulant pathway. PMID- 1311946 TI - Inhibition of cyclic AMP- and cyclic GMP-mediated dilations in isolated arteries by oxidized low density lipoproteins. AB - We studied the effects of native (N) and oxidized (Ox) low density lipoproteins (LDLs) on adenosine 3',5'-cyclic monophosphate (cAMP)-mediated and on guanosine 3',5'-cyclic monophosphate (cGMP)-mediated dilator mechanisms in isolated, perfused human mammary and rabbit femoral arteries. Dilations were induced in preconstricted, deendothelialized segments by either forskolin (Fo) or sodium nitroprusside (SNP) (intraluminal or adventitial application). Lipoproteins (0.5 mg/ml) were administered to the segments from the intraluminal side. N-LDL had no effect on Fo-induced dilation and caused a weak attenuation of SNP-induced dilation only when SNP was also administered into the intraluminal perfusate. In contrast, Ox-LDL inhibited both Fo- and SNP-induced dilation, independent of the route of dilator application. The effects of Ox-LDL were specific for dilation mediated by cyclic nucleotides. Dilation elicited by the Ca2+ antagonist nitrendipine was inhibited neither by N-LDL nor by Ox-LDL. Determination of basal and stimulated (SNP, Fo) cGMP and cAMP content in rabbit femoral segments after preincubation with N-LDL and Ox-LDL revealed a significant decrease of stimulated vascular cGMP and cAMP content by Ox-LDL, whereas N-LDL had no effect. These data indicate that Ox-LDL selectively inhibits vascular smooth muscle relaxation elicited by increases in cyclic nucleotides. This inhibition might contribute to the attenuation of vasodilation in hypercholesterolemia and atherosclerosis. PMID- 1311947 TI - Antithrombotic efficacy of low-molecular-weight heparin in deep arterial injury. AB - Low-molecular-weight heparin subfractions more specifically inhibit factor Xa than thrombin, and they may have advantages over unfractionated heparin in arterial thrombosis. The antithrombotic efficacy of four dosages of a low molecular-weight heparin (CY216 at 100, 200, 400, or 500 Institute Choay units/kg) was compared with unfractionated calcium heparin (100 US Pharmacopeia units/kg) and placebo during deep arterial injury produced by balloon dilatation of the carotid artery in the pig. The acute thrombotic end points were 111In labeled platelet and 125I-labeled fibrinogen/fibrin deposition and macroscopic mural thrombosis; these were related to the anti-factor Xa and antithrombin effects of the heparin preparations. Platelet deposition in segments with deep arterial injury was 42 +/- 28, 22 +/- 5, 29 +/- 12, 9 +/- 2, 9 +/- 2, and 11 +/- 3 x 10(6)/cm2 (mean +/- SEM) for pigs treated with placebo, with 100, 200, 400, and 500 units/kg CY216, and with 100 units/kg unfractionated heparin, respectively. Fibrinogen/fibrin deposition was 35 +/- 8, 19 +/- 2, 19 +/- 4, 21 +/- 3, 14 +/- 4, and 12 +/- 3 molecules x 10(12)/cm2, respectively; deposition was significantly reduced in pigs given 100 units/kg unfractionated heparin compared with placebo (p less than 0.05). Mural thrombosis was present in 74%, 45%, 30%, 14%, 5%, and 9% of deeply injured arterial segments, respectively (p = 0.02). Plasma anti-factor Xa activity and prolongation of the activated partial thromboplastin time (aPTT) with 100 units/kg unfractionated heparin were similar to that produced by 200 units/kg and 500 units/kg CY216, respectively. Thus, low molecular-weight heparin, which predominantly inhibits factor Xa activity, was only moderately effective at reducing platelet thrombus deposition. It was less effective than 100 units/kg unfractionated heparin, except at high dosages, producing similar prolongation of the aPTT and the thrombin time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1311948 TI - Does the EcoRI polymorphism in the human apolipoprotein B gene affect the binding of low density lipoprotein to the low density lipoprotein receptor? AB - In human populations, there is an association between coronary artery disease and a polymorphism in the apolipoprotein B (apo B) gene detected with the enzyme EcoRI. This polymorphism gives rise to two apo B alleles, one (E+) encoding glutamic acid and the other (E-) encoding lysine at position 4,154 in apo B-100, the protein of low density lipoprotein (LDL). We have tested the hypothesis that this amino acid substitution indirectly influences proneness to coronary artery disease by affecting the binding of LDL to LDL receptors. The receptor-binding affinities of LDLs from eight pairs of subjects with genotypes E+/+ and E-/- who were matched for other apo B genotypes were determined in vitro. There was no significant difference between the binding affinities of LDLs from the two groups of subjects. Our results strongly suggest that the amino acid at position 4,154 does not influence the function of the receptor-binding domain in apo B-100 and that the association between coronary artery disease and the EcoRI polymorphism is not mediated by an effect of the polymorphism on serum LDL concentration. In view of our findings, it would be of interest to examine the effect of the amino acid substitution on the binding of LDL to arterial proteoglycans and on the oxidizability of LDL by cells in culture. PMID- 1311949 TI - Isoforms of cytochrome c oxidase in tissues and cell lines of the mouse. AB - The subunit pattern of immunopurified cytochrome c oxidase from cultured mouse cells and mature tissues of the mouse was investigated by electrophoretic analysis. In mature tissues two forms of cytochrome c oxidase could clearly be identified on the basis of differences in morbidity or staining intensity of subunits VIa and VIII. One form was present in muscle and heart, and the other in liver, kidney and spleen. In lung both forms were found. In the thymus, subunit VIII showed the characteristics of subunit VIII found in muscle and heart, whereas subunit VIa resembled subunit VIa found in liver. This suggest the existence of a third cytochrome c oxidase isoform. The subunits of cytochrome c oxidase from cultured cell lines showed no differences between the various cell lines and resembled those of mature mouse liver tissue. The cytochrome c oxidase isoform from cultured proliferating cells might therefore be the same as the one found in liver. Alternatively, it might represent either a normally occurring fetal isoform, or a form specific for poorly differentiated cultured cells. PMID- 1311950 TI - Formation of supported planar bilayers by fusion of vesicles to supported phospholipid monolayers. AB - A technique for the production of supported phospholipid bilayers by adsorption and fusion of small unilamellar vesicles to supported phospholipid monolayers on quartz is described. The physical properties of these supported bilayers are compared with those of supported bilayers which are prepared by Langmuir-Blodgett deposition or by direct vesicle fusion to plain quartz slides. The time courses of vesicle adsorption, fusion and desorption are followed by total internal reflection fluorescence microscopy and the lateral diffusion of the lipids in the adsorbed layers by fluorescence recovery after photobleaching. Complete supported bilayers can be formed with phosphatidylcholine vesicles at concentrations as low as 35 microM. However, the adsorption, fusion and desorption kinetics strongly depend on the used lipid, NaCl and Ca2+ concentrations. Asymmetric negatively charged supported bilayers can be produced by incubating a phosphatidylcholine monolayer with vesicles composed of 80% phosphatidylcholine and 20% phosphatidylglycerol. Adsorbed vesicles can be removed by washing with buffer. The measured fluorescence intensities after washing are consistent with single supported bilayers. The lateral diffusion experiments confirm that continuous extended bilayers are formed by the monolayer-fusion technique. The measured lateral diffusion coefficient of NBD-labeled phosphatidylethanolamine is (3.6 +/- 0.5) x 10(-8) cm2/s in supported phosphatidylcholine bilayers, independent of the method by which the bilayers were prepared. PMID- 1311951 TI - CDP-choline: 1,2-diacylglycerol cholinephosphotransferase from rat liver microsomes. II. Photoaffinity labeling by radioactive CDP-choline analogs. AB - Photoaffinity labeling of cholinephosphotransferase from rat liver microsomes directly by its substrate, [32P]CDP-choline or by a synthetic photoreactive CDP choline analog, 3'(2')-O-(4-benzoyl)benzoyl [32P]CDP-choline (BB-[32P]CDP choline), was examined for the possible identification of its molecular form on subsequent SDS-PAGE followed by 32P-autoradiography. When the partially purified cholinephosphotransferase was photoirradiated in the presence of [32P]CDP choline, a considerable amount of 32P-radioactivity was incorporated into the TCA insoluble component. This incorporation was dependent on irradiation time, Mg2+ or Mn(2+)-requiring and inhibited strongly by the presence of Ca2+. Either CDP choline or CDP-ethanolamine inhibited the ultraviolet irradiation-dependent incorporation of 32P-radioactivity into the TCA-insoluble component in a dose dependent manner, whereas neither phosphocholine or 5'-CDP had any effect on this process. These results strongly suggested that the observed 32P-incorporation from [32P]CDP-choline into the protein component could be a consequence of the covalent interaction between cholinephosphotransferase and its substrate, [32P]CDP-choline. Two polypeptides, 25 kDa and 18 kDa, with high 32P radioactivity were clearly identified on a SDS gel after the direct photoaffinity labeling with [32P]CDP-choline for more than 5 min of ultraviolet irradiation. On the other hand, when BB-[32P]CDP-choline was used as a photoaffinity ligand, a single polypeptide with apparent molecular size of 55 kDa could be rapidly photolabeled within 2.5 min, then this band gradually lost its 32P-radioactivity with increasing time of ultraviolet irradiation. Thus, the overall results strongly indicated that cholinephosphotransferase in rat liver microsomes exists most likely as a 55 kDa polypeptide (or subunit) and that 25 kDa and 18 kDa peptides identified after the direct photoaffinity labeling with [32P]CDP-choline were probably the photo-cleavage products of cholinephosphotransferase during the prolonged ultraviolet irradiation, both of which could contain the catalytic domain of the original enzyme protein(s). PMID- 1311952 TI - Soybean phospholipid dependent reductions in triacylglycerol concentration and synthesis in the liver of fasted-refed rats. AB - The effect of dietary soybean phospholipid on the activities of hepatic triacylglycerol-synthesizing enzymes was compared with soybean oil in fasted refed rats. Soybean oil at the dietary level corresponding to 20% but not at 5% fatty acid level (21.2 and 5.3% on weight bases, respectively) significantly decreased liver microsomal diacylglycerol acyltransferase activities measured with the endogenous diacylglycerol substrate. Dietary soybean phospholipid even at the dietary level corresponding to 2% fatty acids (3.4% on weight base) significantly decreased the acyltransferase activities measured with endogenous substrate. The dietary phospholipid further decreased the parameter as the dietary level increased, and at the 5% fatty acid level, it was lower than that obtained with soybean oil at 20% fatty acid level. Soybean oil and phospholipid decreased the diacylglycerol acyltransferase activities measured with the saturating concentration of exogenous dioleoylglycerol substrate only when the activities were expressed in terms of total activity (mumol/min per liver) but to much lesser extents. Dietary phospholipid compared to the oil profoundly decreased not only hepatic triacylglycerol but also microsomal diacylglycerol levels. It was indicated that the availability of microsomal diacylglycerol as the substrate for diacylglycerol transferase is the critical determinant in regulating hepatic triacylglycerol synthesis and concentration in this experimental situation. Alterations in the activities of microsomal glycerol 3 phosphate acyltransferase and of the enzymes in fatty acid synthesis could account for the phospholipid-dependent decrease in the microsomal concentration of this intermediate in triacylglycerol synthesis. PMID- 1311953 TI - Correlation between intracellular cAMP levels and phospholipids of Microsporum gypseum. AB - Atropine, a modulator of cAMP has been used to examine the relationship between phospholipids and intracellular levels of cAMP in Microsporum gypseum. A decreased phospholipid content was observed in atropine grown cells as a result of reduced levels of intracellular cAMP. This decline was caused by the inhibitory effect of atropine on adenylate cyclase. Lowered phospholipid content was supported by decreased [14C]acetate incorporation as well as reduced activities of key enzymes of phospholipid biosynthesis. In vitro supplementation of atropine in control cells also caused inhibition in lipid synthesis indicating similar effects of atropine and its metabolites. These results in conjunction with our previous report, in which enhanced levels of cAMP resulted in increased phospholipid synthesis, suggest a direct correlation between phospholipid biosynthesis and intracellular levels of cAMP in M. gypseum. PMID- 1311954 TI - Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences. AB - Complementary DNA encoding rat protein phosphatase 2C alpha was obtained from a liver library and used to isolate the homologous cDNAs from rabbit liver and human teratocarcinoma libraries. The amino acid sequences of the three enzymes deduced from the cDNA (382 amino acids) were extremely similar (greater than 99% identity), the maximum number of differences (between rat and human) being four. Amino acid sequences of peptides corresponding to 238 residues (61%) of the protein phosphatase 2C beta isoform from rabbit skeletal muscle were determined and showed 12 differences from the recently published sequence of the rat liver enzyme deduced from the cDNA (95% identity). PMID- 1311955 TI - Cloning of the human activin receptor cDNA reveals high evolutionary conservation. AB - The entire coding region of the human activin receptor was obtained from a human testis cDNA library. Analysis of the 1539 nucleotide (513 amino acid) sequence of the receptor reveals that there are only 83 nucleotide differences compared to the coding sequence of the mouse activin receptor. Similar to its ligands, the amino acid sequence of the activin receptor is highly conserved with only two conservative amino acid differences (Lys-39 and Val-92 in human versus Arg-39 and Ile-92 in the mouse). This high degree of conservation of the activin receptor illustrates a strong evolutionary selection and confirms that activin and its receptor play an important role in development. PMID- 1311957 TI - Interleukin 1 and phorbol 12-myristate 13-acetate induce collagenase and PGE2 production through a PKC-independent mechanism in chondrocytes. AB - In the present study we demonstrate that interleukin 1 (IL 1) and phorbol 12 myristate 13-acetate (PMA) stimulate collagenase production by bovine chondrocytes in monolayer culture. Since it has been well established that PMA stimulates protein kinase C (PKC), we examined whether IL 1 and PMA also stimulate PKC in chondrocytes. In agreement with other studies, PMA induced the translocation of PKC, reflecting PKC activation by PMA. In contrast, IL 1 did not induce the translocation of PKC. Both IL 1 and PMA stimulated the release of [14C]arachidonic acid from chondrocyte phospholipids, suggesting that both agents stimulate phospholipase A2 (PLA2). Concomitantly, IL 1 and PMA also induced a pronounced increase in the production of PGE2. Pre-incubation of chondrocytes with staurosporine, a PKC inhibitor, did not affect the stimulation of collagenase production by IL 1 and only minimally that induced by PMA. Similarly, high concentrations of staurosporine did not inhibit prostaglandin E2 (PGE2) production induced by IL 1 or PMA. These data show that IL 1 and PMA stimulate the PLA2 pathway and collagenase production, however, these processes can occur in the absence of PKC activation. PMID- 1311956 TI - Regulation of the Escherichia coli lac operon expressed in human cells. AB - We have investigated the use of various Epstein-Barr virus (EBV)-based vectors bearing the two components of the Escherichia coli lac operator-repressor (lacO, lacI) complex. Our aim was to develop a model system of gene expression by looking at the transcription of the bacterial beta-galactosidase coding gene (lacZ) in 293 human embryonic kidney cells. Several vectors have been built carrying different promoters upstream of the lacI and lacZ genes and in which natural or synthetic operator sequences were inserted in the 5' part of the lacZ gene. In transient expression assays we achieved efficient lacZ gene repression which could be released by the specific inducer isopropyl beta-D-thiogalactoside (IPTG). A stable transformed cell line carrying two EBV-derived plasmids with the building blocks of the lac operator/repressor system was established. This cell line allowed us to achieve a wide range of lacZ gene regulation. In this cell line IPTG alone could remove the repression to trigger a 5-fold increase of lacZ expression. Heavy metal ions, which induced the mouse metallothionein I promoter located upstream of the lacZ gene, added together with IPTG gave rise to a 40 fold induction of lacZ expression. PMID- 1311958 TI - Extracellular ATP and cell signalling. PMID- 1311959 TI - Mechanisms by which extracellular ATP and UTP stimulate the release of prostacyclin from bovine pulmonary artery endothelial cells. AB - Extracellular ATP and UTP caused increases in the concentration of cytoplasmic free calcium ([Ca2+]i) and the intracellular level of inositol 1,4,5 trisphosphate (IP3), a second messenger for calcium mobilization, prior to the release of prostacyclin (PGI2) from cultured bovine pulmonary artery endothelial (BPAE) cells. The agonist specificity and dose-dependence were similar for nucleotide-mediated increases in IP3 levels, [Ca2+]i and PGI2 release. An increase in [Ca2+]; and PGI2 release was observed after addition of ionomycin, a calcium ionophore, to BPAE cells incubated in a calcium-free medium. The addition of ATP to the ionomycin-treated cells caused no further increase in [Ca2+]i or PGI2 release. The inability of ATP to cause an increase in [Ca2+]i or PGI2 release in ionomycin-treated cells was apparently due to the ionomycin-dependent depletion of intracellular calcium stores since the subsequent addition of extracellular calcium caused a significant increase in both [Ca2+]i and PGI2 release. Introduction of BAPTA, a calcium buffer, into BPAE cells inhibited ATP mediated increases in [Ca2+]i and PGI2 release, further evidence that PGI2 release is dependent upon an increase in [Ca2+]i. The increase in [Ca2+]i elicited by ATP apparently caused the activation of a calmodulin-dependent phospholipase A2 since trifluoperazine, an inhibitor of calmodulin, and quinacrine, an inhibitor of phospholipase A2, prevented the stimulation of PGI2 release by ATP. Furthermore, ATP caused the specific hydrolysis of [14C]arachidonyl-labeled phosphatidylcholine and the generation of free arachidonic acid, the rate-limiting substrate for PGI2 synthesis, prior to the release of PGI2 from BPAE cells. These findings suggest that the increase in PGI2 release elicited by ATP and UTP is at least partially dependent upon a phospholipase C-mediated increase in [Ca2+]i and the subsequent activation of a phosphatidylcholine-specific phospholipase A2. ATP analogs modified in the adenine base or phosphate moiety caused PGI2 release with a rank order of agonist potency of adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) greater than 2 methylthioATP (2-MeSATP) greater than ATP, whereas alpha, beta methyleneATP and beta, gamma methyleneATP had no effect on PGI2 release. PMID- 1311960 TI - Release of carrot plasma membrane-associated phosphatidylinositol kinase by phospholipase A2 and activation by a 70 kDa protein. AB - Plasma membranes were isolated from carrot (Daucus carota L.) cells grown in suspension culture and treated with phospholipase A2 from snake or bee venom for 10 min. As a result of this treatment, phosphatidylinositol kinase activity was recovered in the soluble fraction. There was no detectable diacylglycerol kinase or phosphatidylinositol monophosphate kinase activity released from the membranes after the phospholipase A2 treatment. Treating the plasma membranes with phospholipase C or D did not release PI kinase activity. The phospholipase A2 released PI kinase was activated over 2-fold by a heat stable, soluble 70 kDa protein. The partially purified 70 kDa activator increases the Vmax but does not affect the Km of the phospholipase A2-released PI kinase. PMID- 1311961 TI - Genital papillomavirus infection in women treated for chlamydial infection. AB - Samples for chlamydia testing were taken from 298 and PAP smear from 284 non pregnant sexually active young women in a midwife-run family planning dervice. Chlamydia was found in 36 (12.1%). Three women (1.1%) had cytological atypia corresponding to CIN I or II. Koilocytosis was seen in 9 smears (2.8%). Thirty two of the chlamydia-positive women were followed for a mean of 15 months by a gynaecologist with chlamydia tests, colposcopy, PAP-smears and in some cases biopsies. There were 7 reinfections with chlamydia (22%). Signs of genital papillomavirus infection (GPVI) were found in 24 of the 32 chlamydia cases during follow-up. Twenty chlamydia-positive patients had abnormal colposcopy, 15 of them had other changes suggestive of GPVI, seven of these had CIN I or II. At follow up 6 patients had cytologic atypia (18.8%) compared with the average 1.5% in this department during this period. Among 12 patients with normal colposcopy there were no cytological changes. Chlamydial infection calls for increased alertness regarding abnormal vaginal cytology even among young patients not commonly included in PAP smear screening programmes. PMID- 1311962 TI - Prevalence of hepatitis C antibodies (HCV) in a dialysis population at one center. AB - Hepatitis C (HC) has been recently diagnosed by determination of specific antibodies that represent the former so-called non-A, non-B hepatitis. We studied the prevalence of plasma HCV antibodies among 61 unselected patients on hemodialysis (HD) and 43 on continuous ambulatory peritoneal dialysis (CAPD). Plasma C-antibodies were determined through the ELISA test system. Transfusion policy was the same in both groups. The prevalence of hepatitis C virus antibodies was significantly higher in hemodialysis patients than among those on CAPD. Time on dialysis, previous blood transfusions, and renal transplantation seem to increase the prevalence of C hepatitis antibodies among hemodialysis patients. The effect of these parameters on CAPD was smaller. Understanding the reasons for these differences may help prevent this disease among dialysis patients. PMID- 1311963 TI - The prevalence of hepatitis C virus antibodies in patients treated with continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: To assess the prevalence of anti-HCV (hepatitis C virus antibodies) in continuous ambulatory peritoneal dialysis (CAPD) patients and staff members. DESIGN: Fifty-nine serum samples were collected and tested by an enzyme immunoassay for anti-HCV. Records and past history of blood transfusion and hemodialysis were reviewed. Results were analyzed using the Fisher's exact test. SETTING: A medical college-operated teaching hospital. PARTICIPANTS: Fifty-two patients and 7 staff members from the Chang Gung Memorial Hospital CAPD unit were studied. RESULTS: Anti-HCV prevalence in patients and staff were 15.4% and 0%. A history of maintenance hemodialysis was associated with a higher prevalence of anti-HCV (33.3% versus 5.9% without hemodialysis, p = 0.015). The prevalence of anti-HCV did not increase with longer CAPD duration. Among those with an episode of hepatitis, higher prevalence of anti-HCV was observed (57.1% versus 8.9% without hepatitis, p = 0.0073). CONCLUSION: HCV is an important agent of hepatitis in CAPD patients. The risk of HCV infection among CAPD staff members is negligible. CAPD offers better control of HCV infection among patients with end stage renal failure. PMID- 1311964 TI - Neuroendocrine and behavioral responses to challenge with the indirect serotonin agonist dl-fenfluramine in adults with obsessive-compulsive disorder. AB - Neuroendocrine and behavioral responses to a single 60-mg oral dose of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated adults with obsessive-compulsive disorder (OCD) and neuroendocrine results contrasted with those in normal control subjects. Net fenfluramine-induced prolactin release did not differ significantly between OCD patients and normal controls. Prolactin responses in the OCD group were not significantly correlated with baseline Yale Brown Obsessive Compulsive Scale scores for either obsessions or compulsions, but were positively correlated with the baseline Hamilton Depression Scale score and Hamilton Anxiety Scale score. No clear difference in the severity of patients' obsessions or compulsions was found following challenge with fenfluramine versus placebo. Although the present study does not demonstrate a serotonergic abnormality in OCD, this may be more a reflection of limitations of the test procedures than evidence that central nervous system (CNS) serotonergic function is normal in the disorder. PMID- 1311965 TI - Early-stage squamous cell and adenocarcinoma of the cervix. AB - Articles on early-stage squamous cell and adenocarcinoma of the cervix published between August 1990 and July 1991 are reviewed. A new monoclonal antibody used to distinguish endocervical from endometrial differentiation is described, as well as a histochemical means of distinguishing in situ from invasive adenocarcinoma. In vitro and in vivo studies of cell lines immortalized with human papillomavirus DNA are described with a discussion of the mechanism of the development of malignancy. An animal model to test and develop an anti-human papillomavirus vaccine is presented. The epidemiology of adenocarcinoma is also reviewed, and the development of invasive carcinoma after conservative therapy or conization for dysplasia is discussed. Computed tomography scanning has been found to be no more accurate than examination for staging of early cervical cancer. Several studies in the review period have evaluated risk factors for recurrent disease in patients treated for early-stage cervical cancer, including a prospective surgical pathologic study by the Gynecologic Oncology Group. The optimal treatment of early stage I adenocarcinoma of the cervix is discussed, comparing the efficacy of primary surgical therapy with the efficacy of radiation therapy. The risk of ovarian metastases in patients with early-stage cervical cancer is very low for both squamous cell and adenocarcinoma. The surgical technique and efficacy of laparoscopic pelvic lymphadenectomy for patients with early-stage cervical cancer are discussed. Lateral transposition of the ovaries at the time of radical hysterectomy for cervical cancer has significant potential benefits but also risks. Finally, surveillance methods that detect recurrent cervical cancer after treatment for early-stage disease are discussed. PMID- 1311966 TI - Relationship between intensity of Opisthorchis viverrini infection and hepatobiliary disease detected by ultrasonography. AB - Twenty-four locality-, age- and sex-matched groups of village residents with no light, moderate and heavy Opisthorchis viverrini infection were examined by ultrasonography. Highly significant differences were observed between the groups in the relative size of the left lobe of the liver and the fasting and post-meal size of the gall-bladder. In addition, indistinct gall-bladder wall, the presence of gall-bladder sludge and strongly enhanced portal vein radicle echoes were most frequently observed in the heavily infected group. Two suspected cases of cholangiocarcinoma were identified from the heavy group. The results highlight the importance of intensity of infection on the frequency and severity of fluke associated hepatobiliary disease. PMID- 1311967 TI - High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan. AB - To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80 g of ethanol daily for 5 years or more. Findings for anti HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.3%) of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/121, 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection. PMID- 1311968 TI - Development of hepatocellular carcinoma in a man with auto-immune chronic active hepatitis. AB - A 57 year old man with auto-immune chronic active hepatitis, regularly treated with immunosuppressive therapy, had hepatocellular carcinoma (HCC) 10 years after diagnosis of the hepatitis. Assays of the hepatitis C virus antibodies against capsid and non-structural proteins revealed seronegativity in serial serum samples of this patient stored in the previous 10 years during follow up. The seronegative hepatitis C antibodies excluded hepatitis C virus as the cause of the HCC. The occurrence of HCC in this case suggests the necessity of surveillance for early detection of liver cancer in patients with auto-immune chronic active hepatitis undergoing long-term immunosuppressive therapy. PMID- 1311969 TI - DNA insertions distinguish the duplicated renin genes of DBA/2 and M. hortulanus mice. AB - In a survey of inbred and wild mouse DNAs for genetic variation at the duplicate renin loci, Ren-1 and Ren-2, a variant Not I hybridization pattern was observed in the wild mouse M. hortulanus. To determine the basis for this variation, the structure of the M. hortulanus renin loci has been examined in detail and compared to that of the inbred strain DBA/2. Overall, the gross features of structure in this chromosomal region are conserved in both Mus species. In particular, the sequence at the recombination site between the linked Ren-1 and Ren-2 loci was found to be identical in both DBA/2 and M. hortulanus, indicating that the renin gene duplication occurred prior to the divergence of ancestors of these mice. Renin flanking sequences in M. hortulanus, however, were found to lack four DNA insertions totaling approximately 10.5 kb which reside near the DBA/2 loci. The postduplication evolution of the mouse renin genes is thus characterized by a number of insertion and/or deletion events within nearby flanking sequences. Analysis of renin expression showed little or no difference between these mice in steady state renin RNA levels in most tissues examined, suggesting that these insertions do not influence expression at those sites. A notable exception is the adrenal gland, in which DBA/2 and M. hortulanus mice exhibit different patterns of developmentally regulated renin expression. PMID- 1311971 TI - Characterization of the endogenous nonecotropic murine leukemia viruses of NZB/B1NJ and SM/J inbred strains. AB - We characterized 84 endogenous nonecotropic proviruses of NZB/B1NJ and SM/J inbred strains by examining proviral junction fragment segregation in recombinant inbred (RI) and backcross mice. Forty-five proviruses were shared with other laboratory strains, but 28 were unique to NZB/B1NJ or SM/J. Proviral loci were located on 17 of the 19 mouse autosomes and on both sex chromosomes. These markers will facilitate gene mapping in the NXSM RI set and contribute to the pursuit of a more complete map of the mouse genome. PMID- 1311970 TI - Identification of transcriptional regulatory activity within the 5' A-type monomer sequence of the mouse LINE-1 retroposon. AB - LINE-1 (L1) is a retroposon found in all mammals. In the mouse, approximately 10% of L1 elements are full-length and can be grouped into two classes, A or F, based upon the type of monomer sequence repeated at the 5' end. In order to test for promoter activity in the 5' end of the A-type mouse L1 element, we cloned several different A-monomers into a promoterless chloramphenicol acetyltransferase (CAT) vector. The A-monomer constructs varied in their ability to regulate transcription of the CAT gene, exhibiting CAT activity 16-37% of that detected with the Rous sarcoma virus promoter and enhancer. A series of A-monomer deletions were tested for their ability to regulate CAT expression and gel retardation experiments were performed to identify regions of the A-monomer that may be involved in L1 transcriptional regulation. A-monomer sequences are usually found repeated 2-5 times at the 5' end of a full-length mouse L1. In the absence of long terminal repeats or an internal promoter, the tandem array of A-monomers may provide a mechanism for A-type L1 elements to generate transcripts containing transcriptional regulatory sequences. PMID- 1311972 TI - The use of over-the-counter preparations by drug users attending an addiction treatment unit. PMID- 1311973 TI - Correlates of human immunodeficiency virus infection in intravenous drug users: are treatment-program samples misleading? AB - Using a community-based sample of 1632 intravenous drug users in Baltimore, Maryland, USA, this study evaluated a possible selection bias faced when studying risk factors for human immunodeficiency virus, type 1 (HIV-1) in intravenous drug users drawn solely from treatment programs. Consenting subjects, recruited by extensive distribution of brochures and word-of-mouth, underwent confidential interviews about drug use behaviors in a setting that was independent of community service agencies. Of 1632 subjects, 275 (17%) were currently enrolled in treatment programs. These subjects were similar in many respects to those not currently in treatment, including HIV-1 seroprevalence; however, they differed in that those not in treatment were more likely to be male, younger and black than those currently in treatment, and to have started injecting drugs more recently. However, associations between HIV-1 seropositivity and a series of demographic and drug-using characteristics were mostly similar in direction and magnitude among subjects currently in treatment and those not in treatment. These results suggest that one-time samples of drug users enrolled in treatment programs do not necessarily present a misleading picture of correlates of HIV-1 seropositivity. PMID- 1311974 TI - Assessment and management of opioid withdrawal symptoms in buprenorphine dependent subjects. AB - The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic. PMID- 1311976 TI - Carcinosarcoma of the submandibular salivary gland. Immunohistochemical findings. AB - Carcinosarcomas of the salivary glands are rare lesions that generally have been associated with benign mixed tumors. The authors report a case of a submandibular gland lesion, which occurred in a 64-year-old man, that was composed of intermingled ductal type adenocarcinoma and osteogenic sarcoma with a large component of osteoclast-like giant cells. The local recurrence of the tumor was entirely sarcomatous with no epithelial component observed. There was no histologic evidence of a preexisting or coexisting pleomorphic adenoma. Immunohistochemical studies confirmed two separate populations of tumor cells, corresponding to the histologic growth pattern. The authors review the literature and discuss histogenetic implications of distinction between de novo carcinosarcoma and carcinosarcoma in association with pleomorphic adenoma. PMID- 1311975 TI - The changing face of gastrointestinal cancer. PMID- 1311977 TI - Cereal fiber, calcium, and colorectal cancer. AB - Food intake during the preceding 15 years was evaluated in detail in 41 patients treated for colorectal cancer and an equal number of matched control subjects by means of a dietary history technique that permitted quantitation of nutrients. Dietary habits of the control group could be compared against two larger groups of 371 hospital control and 430 population control subjects. Patients with cancer, who were interviewed after complete recovery from surgery, consumed more fat, protein, and carbohydrates, and thus more energy, than control subjects although these differences were not statistically significant. Per unit energy, the habitual diet of patients with cancer contained less cereal fiber (P less than 0.001), less riboflavin (P less than 0.05), less calcium (P less than 0.05), and less phosphorus (P less than 0.05) than the diet of the control subjects. A high intake of either cereal fiber, total fiber, calcium, and phosphorus in relation to energy intake was found to be associated with a reduced risk ratio of colorectal cancer. For colon cancer separately, a high intake of calcium and cereal fiber was associated with a reduced risk ratio. For rectal cancer, a high intake of total fiber and cereal fiber was associated with a reduced risk ratio. High alcohol consumption correlated with an increased risk ratio. These data are compatible with previous Scandinavian studies relating food consumption to the incidence and mortality of colorectal cancer. PMID- 1311978 TI - The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study. AB - To investigate the role of hepatitis B (HBV) and C viruses (HCV) in hepatocellular carcinoma (HCC) in an HBV endemic area and elucidate the interaction of these two viruses, a case-control study of 128 patients with HCC and 384 age-matched and sex-matched control subjects was done. The positive rates of hepatitis B surface antigen (HBsAg, 77.3%, 99 of 128) and anti-HCV (19.5%, 25 of 128) in patients with HCC were significantly higher than in control subjects (P less than 0.001). Both HBsAg and anti-HCV were important risk factors for HCC (relative risks, 13.96 and 27.12, respectively), and the risk for HCC was elevated significantly to 40.05 (95% confidence interval, 12.57 to 127.6) when HBsAg and anti-HCV were considered simultaneously. These results suggested that HBV and HCV were associated highly with HCC in an HBV endemic area and that these two viruses might contribute independent but synergistic effects to the pathogenesis of HCC. PMID- 1311979 TI - Radioimmunodetection and autoradiographic localization of monoclonal antibody against human hepatocellular carcinoma in xenografts. AB - The monoclonal antibody against human hepatocellular carcinoma, HAb23, was conjugated with radioiodine and injected into nude mice with human hepatoma xenografts. After 4 to 5 days, the nude mice were scanned by emission computerized topography. The results showed that the xenografts were distinguished clearly. The tumor-liver and tumor-blood ratios were 1.94 to 3.66 and 0.56 to 1.65, respectively. Autoradiography showed that the HAb23 was localized mainly on the surface membrane and tubulovesicular systems of the tumor cells. PMID- 1311980 TI - Establishment and characterization of a panel of human lung cancer cell lines. AB - The establishment and characterization of 11 human lung cancer cell lines are described in this article. Nine of these cell lines were established over a 5 year period, from 1983 to 1988, from patients treated at the Kingston Regional Cancer Centre. These include eight definite or probable small cell lung cancer (SCLC) lines and one adenocarcinoma line. In addition, two other SCLC cell lines were characterized. All of the lines have been in continuous culture for more than 2 years. The clinical histories of the patients from whom the cell lines were derived are outlined here. Several features of the cell lines are presented, including the following: (1) a comparison of the histologic features of the cell lines with the original biopsy specimens; (2) the expression of various markers, including cytokeratin, carcinoembryonic antigen, calcitonin, and neuron-specific enolase; (3) activities of the enzymes l-dopa decarboxylase and the brain isoenzyme of creatine kinase; (4) growth characteristics; (5) cloning efficiency in soft agar; (6) tumorigenicity in nude mice; and (7) cytogenetic studies. These cell lines, obtained directly from patients with a spectrum of drug-sensitive and drug-resistant tumors, will be valuable in vitro models of sensitivity and resistance to chemotherapy in lung cancer. PMID- 1311981 TI - Small cell carcinoma of the lung. Treatment in the community. AB - The results of nonprotocol treatment of 232 patients with small cell lung cancer seen by a group of community-based medical oncologists over a 13-year period were evaluated. Factors associated with improved survival also were assessed. The following patient characteristics significantly improved survival: limited stage of disease at diagnosis, treatment of extensive (but not limited) disease with regimens including etoposide and cisplatin, tumor resection, age younger than 70 years, radiation therapy to the chest, and female sex (extensive disease only). Comparison of the data from this study with published results of protocol studies showed similar outcomes. PMID- 1311982 TI - Expression and growth-promoting effect of adult T-cell leukemia-derived factor. A human thioredoxin homologue in hepatocellular carcinoma. AB - Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin 2 receptor inducer, is a human thioredoxin homologue. ADF is detected in many malignant tissues and has a growth-promoting effect on transformed cells. In this study, ADF expression was examined immunohistochemically in human liver cell lines and liver tissues, and its growth-promoting effect was tested on human hepatoma cells. On three liver cell line--PLC/PRF/5, HepG2, and Chang liver cells -ADF stained positively and also was detected by immunoblotting. ADF had strong staining in the fetal liver (n = 8), although it was faint in the normal adult liver (n = 6). In hepatocellular carcinoma (n = 25), ADF expression generally was enhanced and was very strong in 52% (13 of 25) of the cases, although it was moderate in cases of chronic hepatitis or cirrhosis. ADF augmented the growth of PLC/PRF/5 cells and showed an additive effect with epidermal growth factor. These results indicate possible involvement of ADF in cell activation and growth of hepatocytes, as is the case with lymphocytes. PMID- 1311983 TI - Prognostic factors in 227 patients with malignant fibrous histiocytoma. AB - Malignant fibrous histiocytoma, the major subset of soft tissue sarcomas, was examined for prognostic factors that could influence clinical management and research. Two hundred twenty-seven patients with localized disease, having surgery as the principal modality, were reviewed retrospectively to identify clinical outcomes. The mean age of the patients was 54 years. Extremities were the primary tumor site in 157 patients (62.2%). Overall survival rate was 50%, including 38 patients who died of other causes. Distant metastases were most common to the lung (90%). Local recurrence alone occurred in 37 patients (16%), distant metastases alone in 52 (23%), and distant metastases with local recurrence in 25 (11%). The primary tumor size indicated the 5-year survival rate: tumors smaller than 5 cm had a survival rate of 82%; 5 to 10 cm, 68%; and larger than 10 cm, 51%. Intermediate-grade tumors yielded a 5-year survival rate of 80%, and the 5-year survival rate for high-grade tumors was 60%. Survival rates for both grades were affected by size: tumors of high grade and smaller than 5 cm in diameter had a survival rate of 79%; 5 to 10 cm, 63%; and more than 10 cm, 41%. Grade and size emerge as significant prognostic indicators. These variables will prove helpful in treatment decisions and design of clinical studies. PMID- 1311984 TI - Ovarian mucinous tumors frequently express markers of gastric, intestinal, and pancreatobiliary epithelial cells. AB - In 100 mucinous tumors of the ovary (37 benign, 24 borderline, and 39 malignant), the authors determined by histochemical and immunohistochemical techniques the frequencies and patterns of expression of a total of nine markers of gastric, intestinal, and pancreatobiliary duct epithelial cells. M1, a mucin antigen, and cathepsin E (CaE), an aspartic proteinase, two markers of normal gastric superficial/foveolar epithelial cells, were expressed in 95 and 92 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, were found in 79 tumors. All of these tumors also expressed M1 or CaE. DU-PAN-2 and the N-terminal epitope of gastrin-releasing peptide, markers of normal pancreatobiliary duct cells, were found in 70 and 49 tumors, respectively, and CAR-5 and M3SI, markers of intestinal mucin, were expressed in 51 and 30 tumors, respectively. All tumors expressed at least two of the nine markers studied; none expressed PG I, a marker of gastric chief cells. The mucopeptic cell marker, PG II, was significantly more common in benign and borderline than in malignant tumors (P less than 0.005), whereas CAR-5 and M3SI, markers of intestinal mucin, were expressed significantly more often in malignant than in benign and borderline tumors (P less than 0.001). By electron microscopic examination, many tumor cells had fine structural features characteristic of gastric superficial/foveolar and pyloric gland cells, intestinal columnar or goblet cells, and endocervical cells. The results indicate that gastroenteropancreatic cell differentiation--and, in particular, gastric type differentiation--is a prominent feature of ovarian mucinous tumors. PMID- 1311985 TI - Extraneural metastases of infratentorial glioblastoma multiforme to the peritoneal cavity. AB - This report describes two autopsy-proven cases of a rare complication of infratentorial glioblastoma multiforme (GBM): metastatic seeding of the peritoneal cavity through ventriculoperitoneal (VP) shunts. Patient 1 was a 13 year-old boy with a pontine GBM, and Patient 2 was a 9-year-old girl with a thoracolumbar spinal cord GBM. Autopsy of both patients demonstrated leptomeningeal gliomatosis encasing the spinal cord and basal structures of the brain, in addition to peritoneal and omental metastases. The pattern of abdominal metastasis seen in these patients is typical of tumors that directly seed the peritoneal cavity and implicates the VP shunt as the vehicle of extraneural spread. Although a rare occurrence, extraneural metastases should be sought in patients with glioma with VP shunts who demonstrate increased abdominal girth, unexplained weight gain, or persistent abdominal pain. PMID- 1311986 TI - An immunohistochemical study of perianal Paget's disease. Possible origins and clinical implications. AB - The histogenesis of perianal Paget's disease is controversial. A clinical and pathologic study was done of a patient with a history of adenocarcinoma of the rectum for whom a subsequent diagnosis of perianal Paget's disease was the sole manifestation of recurrent rectal cancer. Immunohistochemical techniques were used to compare and contrast the original rectal adenocarcinoma with the subsequent perianal skin recurrence confined to the epidermis. Both the rectal adenocarcinoma and the Paget's cells were positive for cytokeratin, epithelial membrane antigen, B72.3, and carcinoembryonic antigen and negative for gross cystic disease fluid protein-15, Leu-M1, CA 125, and S-100 protein. These findings, their relevance to the histogenesis of perianal Paget's disease, and the possible clinical implications are discussed. PMID- 1311987 TI - The lessons of life: keynote address to the nutrition and cancer conference. AB - Some 15 years ago there began to emerge a consensus among epidemiologists that diet might be responsible for 30-60% of cancers in the developed world, in the sense that it should be possible to reduce age-specific incidence rates by this amount by practicable dietary change. Within about 6 years it was also broadly agreed that the principal changes required to bring about this effect were a reduction in the consumption of fat; an increase in the consumption of fruit, green and yellow vegetables, dietary fiber, and some micronutrients; and possibly an improvement in the methods of food preservation. Very small effects, if any, were attributed to food additives and to the pollution of food by trace pesticides, which the public, who accepted much of the consensus advice, have increasingly regarded as important causes of risk. These past conclusions are reviewed in the light of increased knowledge of the etiology of cancer and the trends in its incidence. Contrary to common belief, the trends are broadly encouraging. PMID- 1311988 TI - Dietary fiber-mediated mechanisms in carcinogenesis. AB - Dietary fiber may affect the development of cancers of the gastrointestinal tract and the breast. The biological intermediates studied most have been fecal bile acids; both human and animal studies suggest a tumor-promoting role of bile acids in the development of colon tumors, although there are conflicting data from human studies. Short-chain fatty acids are major fermentation products of bacterial degradation of dietary fiber. If short-chain fatty acids explained the tumor-inhibiting properties of dietary fiber, the readily fermentable fibers such as guar and pectin would be more protective than cellulose and wheat bran, which has not been observed. Because these two hypotheses do not adequately explain modulation of tumor growth by dietary fiber, investigation of other intermediates is indicated. These include physical characteristics of the feces, such as abrasiveness; intestinal microflora; aqueous-phase bile acids, which may represent the bioavailable pool; alterations in mucins; mutagenicity of intestinal contents; alterations in mucosal cytokinetics; activities of enzymes, such as ornithine decarboxylase or aryl hydrocarbon hydroxylase; neurogenic effects caused by changes in intestinal bulk or short-chain fatty acids; gut hormones or other peptide growth factors (local or systemic); enterohepatic circulation of hormones; transit time; pH; or decreased availability of total dietary energy. PMID- 1311989 TI - Aflatoxins as risk factors for hepatocellular carcinoma in humans. AB - On a global basis, primary liver cancer (PLC) is a very prevalent form of cancer. Wide variation of PLC incidence in different areas of the world suggests the involvement of environmental factors in its etiology. Two major classes of risk factors have been identified. Extensive evidence indicates the importance of infection by the hepatitis B virus as a major risk factor for PLC. Because many organic chemicals induce liver cancer in experimental animals, those to which human exposure is known to occur are also of interest with respect to their possible involvement as risk factors for PLC. Particular emphasis has been placed on aflatoxins because of the frequency with which they occur as food contaminants, together with their potency as liver carcinogens for a large number of experimental animals, including subhuman primates. Other mycotoxins, notably sterigmatocystin and fumonisin, also are relatively potent carcinogens for the liver of animals, but little is known about human exposure to them. Epidemiological surveys carried out over the past 25 years in Asia and Africa have revealed a strong statistical association between aflatoxin ingestion and PLC incidence. The combined experimental and epidemiological evidence has led to designation of aflatoxins as human carcinogens according to International Agency for Cancer Research criteria. Collectively, current evidence strongly suggests that PLC is of multifactorial origin, with probable interactions between viral and chemical agents in populations concurrently exposed to both classes of risk factors. Recently developed methods that permit individual monitoring of aflatoxin exposure, hepatitis B virus infection, and genetic damage caused by these agents are being applied in the design of molecular and biochemical epidemiological studies of the etiology of the disease. Application of this methodology may contribute to elucidation of the relative importance of interacting etiological agents in different populations. PMID- 1311990 TI - Modulation of monocytic differentiation of HL-60 cells by inhibitors of protein tyrosine kinases. AB - We showed previously that the expressions of various src family protein tyrosine kinases (PTKs) were induced independently during the monocytic differentiation of HL-60 cells. The role of PTKs was further assessed in the present study by investigating the effects of PTK inhibitors on the differentiation. It was demonstrated that PTK inhibitors such as genistein and herbimycin A modulated monocytic differentiation of HL-60 cells; they inhibited the differentiation induced by TPA, while promoting that induced by vitamin D3 (D3). Immunoblotting analysis of protein molecules which had been phosphorylated on their tyrosine residues demonstrated that TPA induced phosphorylation of certain molecules different from those induced by D3 in HL-60 cells. PTK inhibitors blocked the phosphorylation and modulated differentiation driven by the inducers. These data suggest that PTKs are involved both promotively and suppressively in signaling events that induce monocytic differentiation of HL-60 cells. PMID- 1311991 TI - Autosomal recessive blepharophimosis, ptosis, V-esotropia, syndactyly and short stature. AB - A recessively inherited syndrome of blepharophimosis and ptosis with weakness of extraocular and frontal muscles is reported in six members of three related kindreds. Prognathism, synophrys and thick eyebrows added to a typical facial appearance. Additional findings included short stature, borderline head circumference and toe syndactyly. Borderline mental retardation and anosmia were found in one patient. The clinical features and the mode of inheritance distinguish this syndrome from other blepharophimosis and ptosis syndromes. PMID- 1311992 TI - Antibodies to hepatitis C virus in essential mixed cryoglobulinaemia. AB - Although essential mixed cryoglobulinaemia (EMC) is recognized to be frequently associated with chronic liver disease, aetiology and pathogenesis of liver damage remain unsolved questions. The purpose of this study was to assess the possible causative role of hepatitis C virus (HCV) in the liver impairment occurring in patients with EMC. Twenty-six consecutive EMC patients were evaluated. All patients underwent percutaneous liver biopsy. Anti-HCV antibodies were assayed by ELISA and supported by a recombinant immunoblotting assay (4-RIBA). The prevalence of anti-HCV antibodies in patients with and without chronic active liver disease (CALD) was compared. Anti-HCV antibodies were detected in 13 patients (50%) by ELISA and confirmed in 11 of them (42.3%) by 4-RIBA, the remaining two patients being indeterminate in the supportive assay. CALD correlated significantly with anti-HCV antibodies: indeed, 7/11 (63.6%) anti-HCV+ patients showed histological and clinical pictures of CALD, compared with 1/15 (6.6%) anti-HCV- patients (P less than 0.01). With the exception of the patient who was found to be HBsAg+, no liver tissue expressed hepatitis B virus-related antigens in the hepatocytes. Additional histological findings included discrete lymphoid aggregates in portal tracts, siderosis, fatty changes, hyperplasia of Kupffer cells. It can be concluded that chronic liver damage in EMC is frequently associated with anti-HCV antibodies. Although the cause of EMC remains unknown, this study has obvious implications for clarifying the etiology of associated CALD and further supports the therapeutic use of interferons in this disease. PMID- 1311993 TI - Epstein-Barr virus and HIV play no direct role in persistent generalized lymphadenopathy syndrome. AB - Persistent generalized lymphadenopathy (PGL) and polyclonal B cell activation are features of infection with HIV. Epstein-Barr virus (EBV) and HIV are known to activate B cells in vitro, but whether they are important B cell activators in patients infected with HIV is less clear. In this study, lymph node tissue was obtained from 10 patients with PGL and assessed for evidence of EBV and HIV gene sequences. DNA was extracted and specific viral gene sequences identified using the polymerase chain reaction (PCR). EBV sequences were difficult to detect in the PGL tissue, with a signal intensity similar to that of other benign and malignant lymphoid conditions not associated with EBV. HIV sequences were also rare in the PGL tissue, consistent with HIV infection of the small number of peripheral blood cells and nodal T cells likely to be present in such a sample. These findings suggest that the polyclonal B cell activation typical of HIV is not driven by direct EBV or HIV infection of B cells. PMID- 1311994 TI - Up-regulation of tumour necrosis factor-alpha receptors on monocytes by desferrioxamine. AB - The effect of endogenously generated reactive oxygen metabolites on the interaction of human blood monocytes with tumour necrosis factor-alpha (TNF alpha) was investigated. Pre-exposure of unactivated human blood monocytes to dimethylthiourea, a scavenger of hydroxyl radical (OH.), or to desferrioxamine (DFX), an iron chelator preventing the synthesis of OH., enhanced the specific binding of 125I-TNF-alpha to its receptors. Scavengers of superoxide anion or hydrogen peroxide were without effect. DFX-induced up-regulation of 125I-TNF alpha binding depended on the concentration of the drug (1-5 mM) and on the duration of the treatment (1-18 h). It was not due to a reduction of receptor occupancy by endogenously generated TNF-alpha. Scatchard analysis of binding data revealed that DFX caused an approximately two-fold increase in the number of type II TNF-alpha receptors, with no change in their affinity. This up-regulation, that did not require synthesis of new proteins, was associated with a decrease in the internalization rate of TNF-alpha receptors, the half-life of which was doubled. Conversely, these findings suggest that OH. generation by monocytes may have a physiological role in reducing the activity of membrane-associated TNF alpha receptors. PMID- 1311996 TI - Clinical applications of molecular biologic screening for human papillomavirus: diagnostic techniques. PMID- 1311997 TI - Parathyroid carcinoma. Report of three cases. AB - Primary or relapsing hyperparathyroidism should not be considered a result only of benign conditions like adenoma or hyperplasia (primary or secondary). Parathyroid carcinoma is often the real cause but, because of its rarity, sometimes it is either overlooked or misdiagnosed. Even histologic classification can be erroneous. Distant metastases or ectopic location of the tumors are another potential cause of misdiagnosis, especially when management is decided without the help of diagnostic imaging modalities, particularly those related to the functional aspect of the tumors or their metastases, such as the Tl-201/Tc 99m subtraction scan and the Tl-201 whole body scan. PMID- 1311995 TI - Vasoactive intestinal peptide stimulates immunoglobulin production and growth of human B cells. AB - The effect of vasoactive intestinal peptide (VIP) on human lymphoblastoid B cell lines and tonsil B cells was studied. VIP increased immunoglobulin production and proliferation by lymphoblastoid B cell line, GM-1056, in a dose-dependent manner. As little as 10(-12) M of VIP was effective, and higher concentrations of VIP induced an approximately five-fold increase in IgA production. Moreover, this enhancement was blocked by VIP antagonist. Similarly, VIP enhanced IgM and IgG production by other lymphoblastoid B cell lines, CBL and IM-9, respectively. In contrast to VIP, another neuropeptide substance P (SP) or somatostatin failed to enhance immunoglobulin production and thymidine uptake. VIP also enhanced IgA production and thymidine uptake by purified tonsil B cells. However, in contrast to B cell lines, VIP failed to enhance IgM and IgG production by tonsil B cells. SP or somatostatin failed to enhance immunoglobulin production or thymidine uptake by tonsil B cells. These results indicate that VIP acts as B cell stimulatory factor and that VIP may also have preferential effect on IgA production on tonsil B cells. PMID- 1311999 TI - The contribution of supine/upright testicular scintigraphy and sonography in the evaluation of an atypical presentation of acute scrotum. PMID- 1311998 TI - Simple procedure for red blood cell labeling with Tc-99m HMPAO. Preliminary clinical results. AB - Clinical applications for Tc-99m HMPAO labeled red blood cells have not been previously reported. The authors describe a simple, aseptic, closed, one-step centrifugal procedure for red blood cell labeling with Tc-99m HMPAO and isolation from whole blood, and they report the preliminary results of using these labeled red blood cells to detect acute gastrointestinal bleeding in 11 patients. Whole blood was radiolabeled with Tc-99m HMPAO preparation and blood cells were separated by centrifugation (30 min, 200 g, 20 degrees C) using Polyprep density gradient medium. Red blood cells contained about 50% of the radioactivity. Four out of the 11 patients imaged with a gamma camera after reinjection of labeled autologous red blood cells showed abnormal accumulation, suggesting gastrointestinal bleeding that was verified at surgery and was at the site of abnormal activity in all cases. Image quality with Tc-99m HMPAO was comparable to that of Tc-99m pertechnetate labeled pretinned red blood cells. Tc-99m HMPAO can be used as a red blood cell labeler; however, its elution rate from red blood cells limits its applicability in some investigations. PMID- 1312000 TI - Detection of Coxsackie B virus myocarditis on Tc-99m PYP myocardial imaging. PMID- 1312001 TI - Localization of Tc-99m MDP in cystosarcoma phyllodes. PMID- 1312002 TI - Dose responses and pharmacokinetics for the angiotensin converting enzyme inhibitor quinapril. AB - Single doses of the angiotensin converting enzyme (ACE) inhibitor quinapril were administered to salt replete normotensive men to investigate pharmacokinetics and dose responses. Maximal ACE inhibition was produced by the 2.5, 5, and 20 mg doses (but not by 0.5 mg), but there was evidence of dose-dependency only for the duration of ACE inhibition. Quinaprilat was detectable in plasma up to 72 hours after all doses and the terminal phase half-life was calculated at 26 +/- 7 hours. Although there were dose-related increases in area under the curve (AUC), the relationships between dose and both AUC and maximum concentration were nonlinear. These findings suggest that quinapril displays the same prolonged terminal phase half-life that is characteristic of other ACE inhibitor drugs. The failure of doses above 2.5 mg to produce any further increase in the magnitude of ACE inhibition is consistent with an maximum effect dose-response relationship, with the obvious implication that higher doses will increase only the duration not the magnitude of response. PMID- 1312003 TI - Differential response of beta-adrenergic receptor-mediated heart rate and aortic blood flow acceleration to timolol. AB - The apparent affinity of beta-adrenergic receptors for timolol in the sinus node and ventricular myocardium was compared in 11 normal male subjects. Sinus nodal function was assessed by heart rate, and left ventricular systolic function was assessed by Doppler-derived aortic blood flow acceleration. The dose of isoproterenol required for a heart rate or acceleration increase of 35% (I35) was determined before and 2 hours after an oral 10 mg dose of timolol. The apparent affinity constant (ka) for timolol binding to the receptor was calculated from the serum timolol concentration and the ratio of the I35 after timolol/I35 before timolol. The I35 for sinus node and ventricular myocardium were not significantly different from one another. The ka for timolol binding to the sinus node (1.14 x 10(6) mol/L), however, was significantly greater (p less than 0.05) than ka for ventricular myocardium (7.85 x 10(5) mol/L). These findings suggest that beta adrenergic receptors in the sinus node may have an overall greater affinity for beta-blocking agents than do receptors in the ventricular myocardium. PMID- 1312004 TI - Long-term ergotamine abuse: effect on adrenergically induced mydriasis. AB - The mydriatic action of sympathomimetic eyedrops after a therapeutic dose of ergotamine was measured in migraine patients with and without histories of long term ergotamine abuse. Mydriasis induced by the postsynaptic alpha 1-agonist phenylephrine was similar in both groups of patients tested, whereas pupillary dilation caused by the release of noradrenaline tyramine was markedly greater in patients with histories of ergotamine abuse. The enhanced response to tyramine disappeared after drug withdrawal. These findings indicate that continuous ergotamine medication causes a reversible alterations in iris sympathetic transmission. This manifestation may reflect a central inhibition of pupillary sympathetic activity. PMID- 1312005 TI - A new chick mitochondrial DNA-binding protein exhibits sequence-specific interaction near heavy-strand replication origin: cleavage activity, stimulation of mtDNA synthesis, and enhancement in transformed fibroblasts. AB - We have identified a new, double-strand-dependent, mtDNA-binding protein in chick embryo fibroblast (CEF) mitochondria (and inner-membrane-matrix preparations) which demonstrates both an exclusive specific affinity for the displacement loop (D-loop) control region of chick mtDNA and intramitochondrial levels that reflect corresponding changes in mtDNA replication activity both in vivo and in vitro. This approximately 36 kDa protein (designated aMDP1, avian mitochondrial DNA binding protein 1) was identified by elution and renaturation following SDS polyacrylamide gel electrophoresis and by direct isolation from specific mtDNA protein complexes excised from mobility shift gels. Analysis of the entire 16.7 kb mt genome determined that a MDP1 mediates cleavage of chick mtDNA in vitro at three H- and two L-strand sequence-specific target sites located within a 90-bp A + T-rich genomic tract, theoretically capable of forming stable secondary structures, approximately 200 bases upstream from the H-strand origin (OH) of replication. Furthermore, gel-isolated aMDP1 relaxes supercoiled mtDNA, and exogenous addition of the protein, in a permeabilized in vitro system, preferentially stimulates the synthesis of H-strand sequences which hybridize to OH-containing fragments. Oncogenic transformation of CEF by Rous sarcoma viruses results in a threefold elevated level of aMDP1, directly correlating with a similarly increased level of mtDNA replication in vivo. Heterologous chick-human cross-competition experiments showed that aMDP1 also selectively interacts with human (HeLa) D-loop region mtDNA, possibly reflective of an evolutionary importance for aMDP1 interaction in the region. Functionally, we hypothesize that aMDP1 may operate in conjunction with other mtDNA-binding proteins, important in replication and transcription, by potentiating duplex unwinding either prior to or during an initial stage of H-strand synthesis. Together, these results suggest that aMDP1 is a good potential candidate for a nucleus-encoded regulatory protein which communicates with the mt genome during the replication process. PMID- 1312006 TI - Lectin-induced differentiation of transformed neuroretinal cells in vitro. AB - The orderly course of chick neuroretinal cell differentiation was disrupted in vitro by infection with a temperature-sensitive strain of the Rous sarcoma virus (LA29). The resulting cell culture LA29NR remained mitotically active at 42 degrees C, yet rapidly adopted a transformed phenotype upon activation of the pp60v-src oncogene product at 37 degrees C. As a further indication of metabolic state, LA29NR cells expressed the protooncogene product c-Fos, as shown by Western blot analysis. Highly proliferative LA29NR cells proved refractory to standard differentiation agents such as cAMP, and prostaglandin E1. In our novel approach, succinylated concanavalin A (SCA), a nontoxic derivative of the lectin concanavalin A, induced dramatic, reversible morphological changes in LA29NR cells, including neurite outgrowth and increased cell-to-cell adhesion. Fluoresceinated SCA appeared to localize to Golgi and lysosomal structures. Cellular response to SCA treatment included decreased growth rate, reversible decrease in the phosphorylation state of a 41-kDa phosphoprotein, and induction of neuron-specific enolase. The glial marker vimentin was also evident in these cultures. These data suggest that SCA is an effective differentiation agent for cells of neuroectodermal origin, permitting neuronal as well as glial phenotypic expression within these cell populations. PMID- 1312007 TI - Inhibition of platelet-derived growth factor-induced mitogenesis and tyrosine kinase activity in cultured bone marrow fibroblasts by tyrphostins. AB - Tyrphostins, which block protein tyrosine kinase activity, were studied for their inhibitory action on platelet-derived growth factor (PDGF)-induced proliferation of human bone marrow fibroblasts. Of the seven tryphostins examined, tyrphostin AG370 was found to be the most potent blocker against PDGF-induced mitogenesis (IC50 = 20 microM). This PTK blocker also blocks mitogenesis induced by epidermal growth factor (IC50 = 50 microM) and human serum (IC50 = 50 microM), but with lower efficacy. In digitonin-permeabilized fibroblasts as well as in intact fibroblasts, tyrphostin AG370 inhibits PDGF receptor autophosphorylation and the tyrosine phosphorylation of intracellular protein substrates (pp120, pp85, and pp75) which coprecipitate with the PDGF receptor. In comparison to AG370, AG18, a potent EGF receptor blocker, was less efficient in inhibiting PDGF-induced proliferation of fibroblasts and phosphorylation of the intracellular protein substrates. Under the conditions in which AG370 inhibits PDGF-induced mitogenesis and phosphorylation, it does not affect [125I]PDGF internalization and enhance [125I]PDGF binding. These findings suggest that AG370, which is an indole tyrphostin, may serve as a model for developing analogues with a therapeutic potential for treatment of diseases which involve abnormal cellular proliferation induced by PDGF. PMID- 1312008 TI - Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases. AB - In vitro erythroid differentiation of mouse erythroleukemia (MEL) cells was induced by combinations of topoisomerase and protein kinase inhibitors. Neither inhibitor alone exhibited inducing activity. Although inhibitors of topoisomerases I and II were equally effective in the synergistic induction of erythroid differentiation, only inhibitors of tyrosine kinases, not of serine/threonine kinases, exhibited synergistic activity. The erythroid differentiation induced by the combination of topoisomerase and protein tyrosine kinase inhibitors was distinguished from that induced by typical erythroid inducing agents such as DMSO or HMBA by (1) earlier hemoglobin accumulation in the cells and (2) insensitivity to specific inhibitors (dexamethasone and sodium orthovanadate) of MEL cell differentiation. PMID- 1312009 TI - Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct. AB - A soluble construct consisting of a plasmid carrying the gene of the SV40 large T antigen and an insulin-poly-L-lysine conjugate is able to selectively transfect PLC/PRF/5 human hepatoma cells which possess insulin receptors. Transfection can be efficiently competed by excess free insulin. To examine intracellular transport of the construct, it was fluorescently labeled and its accumulation on and in cells visualized by video-enhanced microscopy and quantitative confocal laser scanning microscopy. After 2 h at 37 degrees C, the labeled construct was found predominantly in intracellular acidic compartments, with a substantial portion of fluorescence localized both near and in the cell nucleus. Binding, endocytosis, and nuclear localization of the labeled conjugate could all be competed by excess free insulin, thus indicating that entry of the conjugate into cells was specifically mediated by the insulin receptor. PMID- 1312010 TI - Phorbol esters augment polyamine transport by influencing Na(+)-K+ pump in murine leukemia cells. AB - In this report, we elucidate the role of Na(+)-K+ pump in the regulation of polyamine spermidine (Spd) transport in murine leukemia (L 1210) cells in culture. Ouabain, known to bind extracellularly to the alpha-subunit of the Na(+) K+ pump, inhibits the pump activity. The L 1210 cells were found to possess ouabain binding sites at 7.5 fmol/10(6) cells. Ouabain significantly inhibited the Spd uptake in a dose-dependent manner. The maximum inhibition of Spd uptake by ouabain was observed beyond 200 microM. Spd transport was inversely correlated with the [3H]ouabain binding to L 1210 cells: an increase in the saturation of ouabain binding to L 1210 cells resulted in a decrease of the Spd uptake process. Treatment of L 1210 cells with protein kinase C activator phorbol esters increased the Spd transport and, also, ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na(+)-K+ pump. H-7, a protein kinase C inhibitor, significantly inhibited the ouabain-sensitive 86Rb+ uptake by L 1210 cells. Phorbol esters stimulated the level, but not the rate, of 22Na+ influx. Addition of H-7 to L 1210 cells inhibited the 22Na+ influx process. A concomitant phorbol ester-induced increase in 22Na+ influx, [14C]Spd uptake, together with the functioning of Na(+)-K+ pump, indicates the role of the "Na+ cycle" in the regulation of the polyamine transport process. PMID- 1312011 TI - Lipid domain reorganization and receptor events. Results obtained with new fluorescent lipid probes. PMID- 1312012 TI - Receptor-mediated endocytosis of the intrinsic factor-cobalamin complex in HT 29, a human colon carcinoma cell line. AB - A HT 29 cell line derived from human colonic carcinoma was shown to express the intrinsic factor receptor, with about 5000 binding sites per cell and an association constant of 20 x 10(9) 1/mol at pH 7.4 and 4 degrees C. The number of binding sites increased dramatically between 7 and 10 days of culture time. Endocytosis of the intrinsic factor-cobalamin-receptor complex was inhibited by two ways: at 4 degrees C and at 37 degrees C by incubating the cells with vinblastine, monensin and chloroquine. The plasma membrane receptor was cross linked to [57Co]cobalamin-intrinsic factor and solubilized with Triton X-100. The cross-linked complex had a relative molecular mass of 330 kDa in native PAGE. PMID- 1312013 TI - Structural characterization and expression of a brain specific gene encoding chick kainate binding protein. AB - The gene encoding chick kainate-binding protein (c-KBP), a member of the non-NMDA ionotropic glutamate receptor family has been isolated and characterized. The c KBP gene is at least 13 kilobases long and contains 11 exons interrupted by 10 introns. Primer extension and RNase protection studies identified a major transcription initiation site located 117 bases upstream from the initiation methionine codon ATG. Consensus TATA and CCAAT sequences were detected in the putative promoter region. The structure of the c-KBP gene is strikingly different from that of other members of neurotransmitter-gated ion-channels (cloned at present) although the topology of c-KBP consists of four membrane-spanning domains, a structural characteristic of ionotropic receptor subunits. The c-KBP gene was found to be expressed at high levels in chick cerebellar Bergmann glia and at extremely low levels in the forebrain. The limited expression of the c-KBP gene raises important questions concerning the mechanisms governing the regulation of c-KBP gene transcription. PMID- 1312014 TI - Regulation of interleukin-1 receptors on AtT-20 mouse pituitary tumour cells. AB - To study the cellular mechanisms of interleukin-1 (IL-1) in the pituitary corticotroph, we studied the properties of IL-1 receptors on a mouse pituitary ACTH-producing cell line, AtT-20. Scatchard plot analysis revealed a single type of receptor with a Kd (dissociation constant) of 93 pM, and 482 binding sites/cell. [125I]IL-1 alpha binding competed with IL-1 alpha and IL-1 beta in an equimolar fashion. A 24 h pre-incubation with either CRH, epinephrine or nor epinephrine increased the [125I]IL-1 alpha binding sites in the AtT-20 cells and conversely, a similar pre-incubation with either dexamethasone or tumour necrosis factor-alpha (TNF alpha) decreased them without affecting the affinity of the receptors in either case. PMID- 1312015 TI - Relationship between intracellular pH changes, activation of protein kinase C and NADPH oxidase in macrophages. AB - Activation of the superoxide-generating NADPH oxidase by phorbol ester or zymosan induced a cytoplasmic acidification when liver macrophages were incubated in sodium-free media or in the presence of amiloride. Staurosporine or desensitization of protein kinase C inhibited phorbol ester- and zymosan-induced pH changes and generation of superoxide. The intracellular pH remained unchanged in cells incubated in physiological sodium media. Ionomycin and arachidonic acid did not induce a change in intracellular pH or a generation of superoxide. Fluoride, which has been shown to induce a translocation of protein kinase C in these cells, did not elicit superoxide generation but induced a decrease in intracellular pH. These experiments support (1) a role of the Na+/H+ antiporter in macrophages as a metabolic regulator of intracellular pH upon stimulation of the superoxide-generating NADPH oxidase, and (2) suggest an involvement of protein kinase C in this process. PMID- 1312016 TI - Isolation and characterization of polyferredoxin from Methanobacterium thermoautotrophicum. The mvhB gene product of the methylviologen-reducing hydrogenase operon. AB - The methylviologen-reducing hydrogenase operon of Methanobacterium thermoautotrophicum contains an open reading frame, mvhB, the product of which was predicted to have a molecular weight of 44 kDa and to contain as many as 48 iron atoms in 12 [4Fe-4S] clusters, and was therefore suggested to be a polyferredoxin. We have now, for the first time, isolated this polyferredoxin. Its identity with the mvhB gene product was evidenced by a comparison of the N terminal amino acid sequence. The dark-brown protein of apparent molecular weight 44 kDa was found to contain 53 mol Fe and 43 mol acid-labile sulfur per mol. The UV/visible spectrum showed two maxima at 280 nm and 390 nm, and a shoulder at 308 nm. The A390/A280 ratio was 0.73. The molar extinction coefficient at 390 nm was 170,000 M-1.cm-1. In the dithionite reduced state the protein displayed an EPR spectrum like that of [4Fe-4S] clusters. The results indicate that the mvhB gene product is indeed a polyferredoxin. PMID- 1312017 TI - Autocrine receptors for endothelins in the primary culture of endothelial cells of human umbilical vein. AB - Human umbilical vein endothelial cells (HUVECs) in primary culture produced and secreted endothelin 1 (ET-1) actively. Specific binding of [125I]ET-1 to these cells was not detectable because of the saturation of ET receptors with endogenously produced ET-1. However, addition of phosphoramidon, an inhibitor of ET-converting enzyme, to the medium reduced the production of ET-1 and thus the receptors on HUVECs were made available for exogenously added [125I]ET-1. Binding studies using phosphoramidon-treated HUVECs indicated the existence of a non isopeptide-selective type (ETB) of ET receptor with a Kd of 17 pM. This receptor is thought to be involved in ET-induced vasodilation in an autocrine manner in vivo. PMID- 1312018 TI - The 93 kDa protein gephyrin and tubulin associated with the inhibitory glycine receptor are phosphorylated by an endogenous protein kinase. AB - The 93 kDa protein gephyrin is a tubulin binding peripheral membrane protein that is associated with the inhibitory glycine receptor and has been implicated in its anchoring at central synapses. Here, we demonstrate that gephyrin as well as co purifying tubulin are phosphorylated by a kinase activity which is endogenous to highly purified glycine receptor preparations. This kinase phosphorylates serine and threonine residues and utilizes ATP, but not GTP, as phosphate donor. Its activity is not affected by various activators and/or inhibitors of cyclic nucleotide-dependent kinases, calcium/calmodulin-dependent kinases, or protein kinase C. A five-fold stimulation of kinase activity was, however, observed in the presence of poly-lysine. Phosphorylation of gephyrin and/or tubulin might regulate receptor/cytoskeleton interactions at postsynaptic membrane specializations. PMID- 1312019 TI - Sequence motif in control regions of the H+/K+ ATPase alpha and beta subunit genes recognized by gastric specific nuclear protein(s). AB - A nuclear protein(s) from rat or pig stomach recognized a conserved sequence in the 5'-upstream regions of the rat and human H+/K(+)-ATPase alpha subunit genes. A gel retardation assay suggested that part of the binding site was located in the TAATCAGCTG sequence. No nuclear proteins capable of the binding could be detected in other tissues of rat (liver, brain, kidney, spleen and lung) or pig liver. The sequence motif (GATAGC) located 5'-upstream of the beta-subunit gene also seemed to be recognized by the same protein, because the binding of nuclear protein to the sequence motifs in the alpha and beta subunits was mutually competitive. Considering the sense-strand sequence of the binding motif in the alpha-subunit gene, we conclude that (G/C)PuPu(G/C)NGAT(A/T)PuPy is a core sequence motif for the gastric specific DNA binding protein (PCSF, parietal cell specific factor). PMID- 1312020 TI - Concentration-dependent modulation of basic fibroblast growth factor action on multiplication and locomotion of human teratocarcinoma cells. AB - A human teratoma cell line (Tera 2) was grown in serum-free medium, and the population multiplication was stimulated by the addition of 1-10 ng basic fibroblast growth factor (bFGF)/ml. The bFGF-effect was abrogated by the addition of protamine sulphate. When high concentrations of bFGF were added, a preferential effect on cell locomotion was observed. 100 ng bFGF/ml stimulated cell movement but only exerted a marginal effect on cell multiplication. These observed exogenous requirements for multiplication and locomotion were complemented by the expression of bFGF receptors. Scatchard analysis of binding data suggests the existence of a high-affinity and a low-affinity class of receptors. PMID- 1312021 TI - A new cyclopyrophosphate as a bacterial antistressor? AB - In a number of bacteria an unusual glycosyl pyrophosphate (31P NMR signal chemical shift at about -15 ppm) was detected when the cells were subjected to oxidative stress. This substance from Brevibacterium ammoniagenes has now been identified as 2-methyl-butan-1,2,3,4,-tetraol-2,4-cyclopyrophosphate, which is accumulated in the cell under certain conditions in concentrations of of about 50 mM. It is now suggested that this compound is the long sought after bacterial antistressor. PMID- 1312022 TI - Developmental changes in erythropoietin receptor expression of fetal mouse liver. AB - Erythropoietin (EPO) stimulates proliferation and differentiation of late erythroid precursor cells (CFU-E) and thereby determines the rate of erythropoiesis. Liver is the major erythropoietic site in a fetus. We dealt with developmental changes in CFU-E and EPO receptor (EPO-R) of fetal mouse liver. The affinity of the EPO-R to EPO was unchanged during fetal development. The population size of CFU-E, the number of EPO-R per liver cell, and EPO-R mRNA decreased as gestation proceeded, in a pattern indicating that the expression of EPO-R on erythroid precursor cells in fetal mouse liver is governed mostly by the process of mRNA production. PMID- 1312023 TI - Okadaic acid strongly increases gene transcription, mRNA and protein level for the urokinase receptor in human A549 cells. AB - The specific phosphatase inhibitor, okadaic acid, increases the level of mRNA for the receptor for urokinase-type plasminogen activator (u-PAR) in 8 out of 13 human cell lines. The strongest increase (90-fold) was observed in A549 lung carcinoma cells, in which it was partly traced back to an increased transcription of the u-PAR gene. There was a parallel but less pronounced increase in the u-PAR protein level. These findings indicate that u-PAR gene transcription is regulated by one or more factors that are constitutively phosphorylated and are dephosphorylated by okadaic acid-sensitive phosphatases. A lack of additivity of u-PAR induction by okadaic acid and by the protein kinase C activator, PMA, in the A549 cells suggests that the regulatory factors affected by okadaic acid are phosphorylated by protein kinase C. PMID- 1312024 TI - Thromboxane receptor stimulation inhibits adenylate cyclase and reduces cyclic AMP-mediated inhibition of ADP-evoked responses in fura-2-loaded human platelets. AB - Stimulation of human platelets with the thromboxane A2 analogue, U46619, after treatment with prostaglandin E1 or forskolin, reduced the inhibition of ADP evoked Mn2+ influx and the release of Ca2+ from intracellular stores. U46619 decreased the elevated concentration of 3',5'-cyclic AMP in platelets that were pretreated with prostaglandin E1. These results suggest that occupation of prostaglandin H2/thromboxane A2 receptors, like those for other agonists, inhibits adenylate cyclase activity, which can contribute to the promotion of platelet activation. PMID- 1312025 TI - Genomic organization and analysis of the 5' end of the porcine ryanodine receptor gene (ryr1). AB - In this study we describe the isolation of genomic clones of the 5' region of the porcine ryanodine receptor gene, a candidate for malignant hyperthermia in pigs and humans. The recombinants were isolated from a porcine liver, genomic DNA library in phage EMBL3A after screening with PCR amplified DNA fragments. The exon/intron structure of the ryanodine receptor gene was determined by DNA sequencing. Based on the sequence data it was possible to develop a simple test for the detection of malignant hyperthermia susceptible and normal pigs. PMID- 1312026 TI - Mercurial activation of human PMN leucocyte type IV procollagenase (gelatinase). AB - Autoproteolytic activation and processing of human polymorphonuclear leucocyte (PMNL) type IV procollagenase (gelatinase) was initiated by HgCl2 and was investigated by kinetic analysis and N-terminal sequence determination of the reaction products. In the first instance the propeptide domain was lost by subsequent cleavage of the Asp15-Leu16, Glu40-Met41, Leu52-Leu53 and Ala74-Met75 peptide bonds. The PRCGVPD sequence motif (residues Pro78-Asp84), which is conserved in all metalloproteinases and expected to be relevant for latency, remained uncleaved at the activated enzyme. The generated intermediate was further processed by three C-terminal cleavages. The Glu666-Leu667, Ala506-Glu507 and Ala398-Leu399 bonds were hydrolysed successively. From the fragmentation products we were able to conclude that three released fragment peptides contained unpaired free cysteine with the residues Cys497, Cys653, Cys683. Cleavage of the first C-terminal peptide bond resulted in the loss of one of the conserved Cys residues of the hemopexin-like domain, whereas the Cys residue of the PRCGVPD motif was retained at the fully active enzyme. The possibility of an entirely different activation mechanism for PMNL type IV procollagenase is discussed. PMID- 1312027 TI - Acute and long-term effects of insulin-like growth factor I on glucose transporters in muscle cells. Translocation and biosynthesis. AB - Insulin-like growth factor I (IGF-I) rapidly (less than 10 min) stimulated glucose uptake into myotubes of the L6 muscle cell line, at concentrations that act specifically on IGF-I receptors. Uptake remained stimulated at a steady level for 1-2 h, after which a second stimulation occurred. The first phase was insensitive to inhibition of protein synthesis. Subcellular fractionation demonstrated that it was accompanied by translocation of glucose transporters (both GLUT1 and GLUT4) to the plasma membrane from intracellular membranes. Translocation sufficed to explain the first phase increase in glucose transport, and there was no change in the total cellular content of GLUT1 or GLUT4 glucose transporters. The second phase of stimulation was inhibitable by cycloheximide, and involved a net increase in either GLUT1 or GLUT4 transporter content, which was reflected in an increase in transporter number in plasma membranes. These results define a cellular mechanism of metabolic action of IGF-I in muscle cells; furthermore, they suggest that IGF-I has acute metabolic effects that mimic those of insulin, bypassing action on the insulin receptor. PMID- 1312028 TI - Evidence for non-cysteinyl coordination of the [2Fe-2S] cluster in Escherichia coli succinate dehydrogenase. AB - The consequences of replacing Cys65 in the FrdB subunit of Escherichia coli fumarate reductase by Asp or Ala have been investigated in terms of bacterial growth, enzymatic activity, and the ERP/redox properties of the [2Fe-2S] cluster. An aspartic acid residue occupies the equivalent position in E. coli succinate dehydrogenase, and the FrdBCys65Asp mutation has little effect on cell growth, enzyme activity or the physical properties of the Frd [2Fe-2S] cluster. In contrast, the [2Fe-2S] cluster was not observed in the FrdBCys65Ala mutant showing that a coordinating residue is required at this position for assembly of this cluster and significant levels of enzymatic activity. These results support the presence of one non-cysteinyl, oxygenic ligand for the [2Fe-2S] cluster in E. coli succinate dehydrogenase. PMID- 1312029 TI - Evidence for a new extracellular peroxidase. Manganese-inhibited peroxidase from the white-rot fungus Bjerkandera sp. BOS 55. AB - A novel enzyme activity was detected in the extracellular fluid of Bjerkandera sp. BOS 55. The purified enzyme could oxidize several compounds, such as Phenol red, 2,6-dimethoxyphenol (DMP), Poly R-478, ABTS and guaiacol, with H2O2 as an electron acceptor. In contrast, veratryl alcohol was not a substrate. This enzyme also had the capacity to oxidize DMP in the absence of H2O2. With some substrates, a strong inhibition of the peroxidative activity by Mn2+ was observed. Phenol red oxidation was inhibited by 84% with only 1 mM of this metal ion. Because DMP oxidation by this enzyme is only slightly inhibited by Mn2+, this substrate should not be used in assays to detect manganese peroxidase. The enzyme is tentatively named 'Manganese-Inhibited Peroxidase'. PMID- 1312030 TI - Changes in the expression of mRNAs for myogenic factors and other muscle-specific proteins in experimental autoimmune myasthenia gravis. AB - The regulation of genes for acetylcholine receptor (AChR), myogenic factors and other muscle-specific proteins has been analyzed in experimental autoimmune myasthenia gravis (EAMG) and following denervation. The levels of the transcripts for the myogenic factors, MyoD1, myogenin and MRF4, were measured using Northern blot analysis. Myogenin and MRF4 transcript levels were observed to be 3.1- and 2.6-fold higher in muscle of rats with EAMG than in controls, respectively. MyoD1 levels, however, remained unchanged. The increases in AChR, myogenin and MRF4 mRNAs were one order of magnitude higher in 2-week denervated muscle than in the myasthenic muscle. The levels of muscle creatine kinase (MCK), alpha-actin and muscle dystrophin transcripts were also analyzed. Dystrophin levels were found to be 1.7- and 4.7-fold higher in EAMG and denervated muscle, respectively, than in controls; in contrast, MCK and alpha-actin levels remained unchanged. PMID- 1312031 TI - Molecular link between membrane cholesterol and Na+/H+ exchange within human platelets. AB - Incubation of human platelets with cholesterol-poor, cholesterol-normal and cholesterol-rich liposomes revealed that: (i) acquisition or depletion of platelet membrane cholesterol was highly selective; (ii) variation in membrane cholesterol was highly selective. Variation in membrane cholesterol content (cholesterol-to-phospholipid molar ratio from 0.15-1.2) with respect to values found in unmodified normal platelets, was paralleled by the observed changes in amiloride-sensitive cytoplasmic pH, as well as phospholipase A2 activity. However, a decrease in cytoplasmic pH was accompanied by an increase in phospholipase A2 activity; (iii) membrane cholesterol-modulated changes in intra platelet pH, as well as phospholipase A2 activity, was completely inhibited when platelets were pretreated with quinacrine (a specific phospholipase A2 inhibitor) before exposure to various types of liposomes. Although exposure of platelets (pretreated with amiloride) with various types of liposomes resulted in the inhibition of Na+/H+ exchange it had no noticeable effect upon the observed phospholipase A2 activity. Based upon these results we suggest that membrane cholesterol-modulated phospholipase A2 activity may be the basic mechanism responsible for the nature of Na+/H+ exchanger activity observed in cholesterol enriched platelets, leading these platelets to a hypersensitized state. PMID- 1312032 TI - Functional evidence of a transmembrane channel within the Ca2+ transport ATPase of sarcoplasmic reticulum. AB - Ca2+ efflux can be studied conveniently following dilution of sarcoplasmic reticulum (SR) vesicles preloaded with 45Ca2+ by active transport. The rates of efflux are highly dependent on ATPase substrates and cofactors (Pi, Mg2+, Ca2+ and ADP) in the efflux medium. On the other hand, phenothiazines stimulate efflux through a passive permeability channel with no coupled catalytic events. Efflux activation by manipulation of catalytically active ATPase ligands, as well as by the catalytically inactive phenothiazines, can be prevented by thapsigargin, which is a highly specific inhibitor of the Ca(2+)-ATPase. This demonstrates that the passive channel activated by phenothiazines is an integral part of the ATPase, and can operate either uncoupled or coupled to catalytic events. PMID- 1312033 TI - Inhibitory effect of oryzacystatins and a truncation mutant on the replication of poliovirus in infected Vero cells. AB - Poliovirus, a picornavirus family member, requires the processing of its poly protein by its own cysteine proteinase for replication. Oryzacystatin-I and oryzacystatin-II, proteinaceous cysteine proteinase inhibitors (cystatins) of rice seed origin, were found to inhibit the replication of poliovirus effectively in infected Vero cells in vitro. Truncated oryzacystatin-I, which lacks the NH2 terminal 25 amino acid residues of the intact protein, is an even more effective inhibitor, eliciting its effect at concentrations of less than 0.25 nmol/ml. The low molecular weight cysteine proteinase inhibitors, E-64, E-64C and loxistatin, showed no anti-viral effect at any concentration investigated. PMID- 1312034 TI - Endogenous Xenopus-oocyte Ca-channels are regulated by protein kinases A and C. AB - Calcium entry into Xenopus oocyte occurs mainly through voltage-dependent calcium channels. These channels were characterized as belonging to a particular type of calcium channel insensitive to dihydropyridines, omega-conotoxin, and Agelenopsis aperta venom, but blocked by divalent cations (Co, Cd, Ni). Intracellular injection of cAMP, or bath application of phorbol ester, induced a marked increase in calcium current amplitude and a slowing of the inactivation time course. Despite their different pharmacology, endogenous calcium channels, like cardiac or neuronal calcium channels, could be thus regulated by protein kinases A and C. PMID- 1312035 TI - Expression of dihydropyridine-sensitive brain calcium channels in the rat central nervous system. AB - We have localized dihydropyridine (DHP-sensitive calcium channels in rat brain by in situ hybridization and immunohistochemistry. The mRNA for the dihydropyridine sensitive calcium channel alpha 1 subunit (DHPR-B) is prominently localized in neuronal cells in the olfactory bulb, dentate gyrus, hippocampus, arcuate nucleus, paraventricular nucleus, ventromedial nucleus, cerebral cortex, superior colliculus and the cerebellar Purkinje cell layer. Strong expression of DHPR-B mRNA was also found in the pituitary and pineal glands. DHP-sensitive calcium channel alpha 1 subunit distribution has also been examined immunohistochemically with polyclonal antibodies raised against synthetic peptides specific for the DHPR-B alpha 1 subunit protein. The results from immunohistochemistry were in good agreement with those from in situ hybridization. Thus, regional distribution and localization of DHPR-B mRNA and alpha 1 subunit protein in rat brain suggest that this type of DHP-sensitive brain calcium channel may play an important role in excitation-secretion coupling functions in the neuroendocrine system. PMID- 1312037 TI - A possible biological role of the electron transfer between tyrosine and tryptophan. Gating of ion channels. AB - Experiments have demonstrated that four tryptophan residues are located near the tetrodotoxin binding site in Na+ channels, and that conserved tyrosine and tryptophan residues are located in the pore-forming region of voltage-sensitive K+ channels. This paper proposes an activation mechanism involving electron transfer between these residues. The K+ channel may be closed by four tyrosine residues forming hydrogen bonds with each other. After electron transfer, these hydrogen bonds will be broken, thereby opening the channel. The Na+ channel could be activated by a similar mechanism. This idea can be tested directly by observing tyrosine or tryptophan radicals when the channels are in the open state. PMID- 1312036 TI - Molecular characterisation, expression and localisation of human neurokinin-3 receptor. AB - The complete amino acid sequence of the human neurokinin-3 receptor was deduced by DNA sequence analysis of human genomic fragments. Comparison of the predicted primary structure with those for the human neurokinin receptors 1 and 2 shows a highly conserved pattern of seven hydrophobic regions with maximum divergence occurring at the amino- and carboxy-termini. The position of intron-exon junctions are identical to those in other reported neurokinin genes. Using a chimeric genomic-cDNA gene, the human NK-3 receptor was expressed in Xenopus laevis oocytes where it mediates membrane conductance changes in response to its agonist, neurokinin B. More significantly, expression of the gene in mammalian cells resulted in detection of receptor binding as well as neurokinin-stimulated calcium mobilization and arachidonic acid release, all displaying the pharmacological characteristics expected of a neurokinin-3 receptor. By using the polymerase chain reaction we have shown that mRNA for the human neurokinin-3 receptor is expressed predominantly in the central nervous system. PMID- 1312038 TI - Cycloheximide inhibits cellular, but not SV40, DNA replication. AB - We have prepared extracts from cycloheximide-treated cells for the study of simian-virus-40 (SV40)-DNA replication in vitro. When supplemented with the viral initiator protein (large T antigen), these extracts fully supported SV40-DNA replication. We also determined that SV40-DNA replication in vivo is much more resistant to cycloheximide than cellular DNA replication. SV40 encodes its own initiator protein, T antigen, which also functions as a DNA helicase, but depends on cellular functions for all additional replication reactions. Therefore, it appears to be quite likely that cycloheximide affects cellular DNA replication by blocking the synthesis of (a) cellular function(s) that is(are) performed by T antigen in SV40-DNA replication. Indeed, DNA fiber autoradiography and alkaline sucrose gradient centrifugation of pulse-labeled cellular DNA showed that cycloheximide treatment almost completely suppressed replicon initiation and reduced the rate of replication fork movement to about one third of the control. PMID- 1312039 TI - Two-dimensional crystals of membrane-bound gastric H,K-ATPase. AB - Two-dimensional crystallization of membrane-bound H,K-ATPase (EC 3.6.1.36) in vesicle preparations from parietal cells of hog gastric mucosa was induced by an imidazole buffer containing Mg2+ and VO3- ions. A continuous reorganization of the protein molecules started within a few hours by the formation of linear arrays. At later stages confluent two-dimensional crystals were formed. Electron microscopy and image processing showed that these were of a single tetragonal type. The asymmetric unit consisted of one pear-shaped protein domain corresponding to a H,K-ATPase protomer. Through stain-deficient contact regions four adjacent protein units were connected forming a tetrameric structure. PMID- 1312040 TI - Kinetic mechanism of pyruvate decarboxylase. Evidence for a specific protonation of the enzymic intermediate. AB - Decarboxylation of pyruvate by pyruvate decarboxylase (EC 4.1.1.1) was performed in a reaction mixture containing 50% deuterium. The isolated product, acetaldehyde, was investigated directly by 1H NMR and by mass spectrometry after conversion to the 2,4-dinitrophenyl hydrazone. The protium content of 56% at acetaldehyde C1 demonstrates a specific protonation of the corresponding intermediate by the enzyme. Proton inventory studies and enzyme modification indicate the 4' amino group of the coenzyme, thiamine pyrophosphate, in an immonium structure being a possible proton donor. A 'partially concerted' mechanism is suggested for the reaction steps following the decarboxylation. PMID- 1312041 TI - Endothelin stimulates both cAMP formation and phosphatidylinositol hydrolysis in cultured embryonic bovine tracheal cells. AB - Embryonic bovine tracheal (EBTr) cells were found to possess receptors for endothelin (ET) of ET-1-selective (ETA) subtype with a Kd for ET-1 of 114 pM and a Bmax of 12.9 fmol/10(5) cells. Stimulation of EBTr cells with 100 pM to 100 nM ET-1 increased the contents of both inositol phosphates and cAMP in a concentration-dependent manner, indicating that the receptors are coupled to both phosphatidylinositol hydrolysis and cAMP formation in EBTr cells. PMID- 1312042 TI - Prostaglandin F2 alpha decreases the affinity of epidermal growth factor receptors in Swiss mouse 3T3 cells via protein kinase C activation. AB - Prostaglandin F2 alpha (PGF2 alpha) selectively decreases the binding of 125I labelled epidermal growth factor ([125I]EGF) to intact Swiss 3T3 cells. Scatchard analysis reveals that PGF2 alpha decreases the number of high-affinity EGF binding sites without changing the total number of receptors. Prostaglandins E1 (PGE1), E2 (PGE2) or F2 beta (PGF2 beta) do not alter the EGF binding to these cells and do not enhance the PGF2 alpha effect. R-59022 and R-59949, two diacylglycerol kinase inhibitors, enhance the inhibitory effect of PGF2 alpha, whereas down-modulation of protein kinase C (PKC) abolishes the effect. These results indicate that PGF2 alpha decreases EGF binding in Swiss 3T3 cells via PKC activation. PMID- 1312044 TI - Stand up and be counted. PMID- 1312043 TI - Voltage-dependent calcium entry in confluent bovine capillary endothelial cells. AB - Confluent bovine capillary endothelial cells display, when examined for voltage dependent calcium entries using cell-attached channel recordings, two types of Ca2+ channels (4 and 23.5 pS in 110 mM Ba2+) both sensitive to the dihydropyridine Ca agonist BAY K 8644. In contrast to isolated cells, confluent cells display no T-type, low threshold activity, and Ca currents were typically only elicited at very depolarized potentials. In these cells, voltage-dependent calcium entries will only be made operative by substances able to shift their activation towards the resting potential. PMID- 1312045 TI - The nuclear pore: at the crossroads. AB - The nuclear pore complex is at the crossroads of macromolecular traffic across the nuclear envelope. Our knowledge of the mechanism whereby nuclear transport is mediated by the nuclear pore complex is also at a crossroads; a molecular understanding of this process has major implications for applied medical sciences. This becomes obvious with the realization that nuclear proteins are synthesized in the cytoplasm and yet function in the nucleus, and that RNA is transcribed in the nucleus but translated in the cytoplasm. Thus, control of macromolecular traffic across the nuclear membrane is an important means for altering the levels and activities of such molecules as steroid hormone receptors, transcription factors, and enzymes involved in DNA replication. Nuclear proteins have been found to contain nuclear localization sequences (NLS) rich in basic amino acids, which target them for transport through the nuclear pore to the nucleus. It is also clear that a group of novel glycoproteins having a unique carbohydrate modification are required for transport across the nuclear pore complex. However, the mechanism by which the NLS is recognized to mediate transport across the nuclear envelope is poorly understood. It is the aim of this brief review to attempt a synthesis of what is known of this mechanism and what may be newly inferred on the basis of current experimental data. PMID- 1312046 TI - Platelet-activating factor receptor and signal transduction mechanisms. AB - Platelet-activating factor (PAF) is the most potent phospholipid agonist known to date. Radioligand binding studies using [3H]PAF and structurally different PAF antagonists have provided the characteristics of PAF receptor(s) and its heterogeneity. Although efforts have been made to isolate the receptor, it was not until the recent cloning of the PAF receptor that the molecular architecture of the receptor can be visualized. The receptor shows homology to the G protein coupled receptors with seven transmembrane spanning segments. Several serine, threonine, and tyrosine residues are present at the cytoplasmic side, which could serve as sites for phosphorylation. PAF activates GTPase, causes phospholipid turnover via phospholipases C, D, and A2 pathways and also activates protein kinase C and tyrosine kinase. Further, PAF stimulates Ca2+ mobilization some of which may occur via receptor operated channel. Second messengers generated by these multiple signalling pathways play role (or roles) in PAF responses and in the PAF induced expression of primary response genes. These recent developments throw light on the PAF receptor and its signal transduction mechanisms. PMID- 1312047 TI - Receptor tyrosine kinases. AB - A major process through which environmental information is transmitted into cells is via activation of protein tyrosine kinases. Receptor tyrosine kinases contain extracellular ligand recognition, single membrane spanning, and cytoplasmic protein tyrosine kinase domains. The cytoplasmic kinase core is flanked by regulatory segments, which in some family members are also inserted into the core kinase domain. Ligand binding initiates receptor signaling from the cell surface. Activated receptors autophosphorylate to remove alternate substrate/inhibitory constraints and to provide loci for assembly of proteins that contain SRC homology regions. Information is transmitted and diffused by tyrosine phosphorylation of the assembled proteins and of cellular substrates that include protein kinases with specificity for serine/threonine residues. Signaling, which is strictly ligand-dependent, is attenuated by down-regulation of receptors and by feed-back inhibitory loops that involve receptor phosphorylation by cellular kinases. The tyrosine kinase receptors are essential for normal growth, development, and reparative processes. Mutations that remove normal regulatory constraints on the approximately 290 amino acid kinase core of these large proteins result in constitutive function and cell transformation. PMID- 1312048 TI - MR imaging of hepatocellular carcinoma at 1.5 Tesla. AB - The authors investigated the magnetic resonance appearance of hepatocellular carcinoma using a 1.5-Tesla magnet. Twenty-four patients with pathologically proven hepatocellular carcinoma had magnetic resonance imaging (MRI) studies, which were retrospectively reviewed. All patients were imaged with at least two of the following techniques: (1) T1-weighted (T1W), (2) T1-weighted with Gd-DTPA enhancement (T1W-E), (3) T2-weighted (T2W), (4) proton density (PD), and (5) gradient-recalled echoes (GRE). T1W images were equal to T2W images for tumor detection using a grading system. T1W images were slightly better than T2W images for the total number of lesions detected. The other pulsing techniques (PD, T1W E, and GRE) detected fewer lesions. Eight cases of hepatocellular carcinoma (33%) had nonhomogeneous increased signal intensity on both T1W and T2W images. The authors conclude that T1W images are equal to T2W images for detection of hepatocellular carcinoma. The authors also conclude that 33% of hepatocellular carcinomas have an imaging pattern with increased signal intensity on both T1W and T2W images. This pattern is atypical for most other hepatic masses and hence can be used to suggest the mass is hepatocellular carcinoma. PMID- 1312049 TI - Hepatocellular carcinoma with extrahepatic primary neoplasms. AB - We experienced seven cases of hepatocellular carcinoma (HCC) with extrahepatic primary malignant neoplasms (PMNs), which accounted for 7.5% of 93 HCC cases in our department during a 5.5-year investigation period. No common characteristics of the seven patients with extrahepatic PMNs in terms of age, sex, computed tomographic (CT) features of hepatocellular carcinoma, or presence of liver cirrhosis were evident. One of the seven cases had triple PMNs. Extrahepatic PMNs were found in various organs: stomach, colon, kidney, lung, larynx, and esophagus. Attention to extrahepatic organs should be undertaken in the management of HCC. Two patients in hepatic coma died 4 and 6 months after the diagnosis of HCC due to the advanced HCC, and accompanying extrahepatic malignancies were not the primary cause of death. PMID- 1312050 TI - Contribution of CT to characterization of focal nodular hyperplasia of the liver. AB - Our personal series of 20 cases of focal nodular hyperplasia (FNH) of the liver is presented. All lesions were studied with computed tomography (CT), 16 of which with surgical control. Retrospective evaluation of the CT features of the identified FNH, along with those of five hepatocellular adenomas (HCA) and 30 hepatocellular carcinomas (HCC), allowed the definition of specific patterns leading to a correct characterization of FNH in 78% of cases. This greatly reduced the diagnostic errors, with the sole exception of patients with fatty liver in whom nuclear medicine may eventually provide a correct characterization. Fine-needle biopsy is thus only necessary in the dubious cases. A precise diagnostic workup of FNH is necessary, since it may avoid the surgical intervention. PMID- 1312051 TI - Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms. AB - To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors. PMID- 1312052 TI - The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis. AB - The serum levels of CA 125 (cutoff limit, 65 U/ml), CA19.9 (cutoff, 40 U/ml), CA 15.3 (cutoff, 32 U/ml), CA72.4 (cutoff, 3.8 U/ml), and TATI (cutoff, 22 ng/ml) were preoperatively measured in 90 patients with epithelial ovarian cancer and in 254 patients with benign ovarian pathology. CA125 had a sensitivity of 75.6%, a specificity of 86.6%, and a diagnostic accuracy of 83.7% for epithelial ovarian cancer; CA19.9 had a sensitivity of 35.6%, a specificity of 81.1%, and a diagnostic accuracy of 69.2%; CA15.3 had a sensitivity of 57.1%, a specificity of 93.9%, and a diagnostic accuracy of 84.6%; CA72.4 had a sensitivity of 70.7%, a specificity of 91.8%, and a diagnostic accuracy of 86.2%; and TATI had a sensitivity of 47.3%, a specificity of 95.3%, and a diagnostic accuracy of 82.9%. CA 125 was the most sensitive marker for nonmucinous tumors, while CA19.9 and CA72.4 were the antigens more frequently expressed by mucinous malignancies. The sensitivities of serum CA 125 (81.1% vs 50.0%; P = 0.01) and TATI (55.2% vs 18.8%; P = 0.02) were higher in patients above 50 years of age than in younger patients while specificities were quite similar in both age groups. The association of serum CA125 and CA19.9 had a significantly higher sensitivity (93.2% vs 81.1%; P = 0.03) and a slightly lowered specificity (78.9% vs 86.0%; P = 0.46) than CA125 assay alone in the differential diagnosis of ovarian masses in patients above 50 years of age. PMID- 1312054 TI - Detection of the minus strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction: implications for hepatitis C virus replication in infected tissue. AB - The combination of reverse transcription and polymerase chain reaction is a very powerful tool for the detection of hepatitis C virus RNA in sera of patients with hepatitis C virus infection. However, when studying the presence of this virus in tissue using polymerase chain reaction, it may be difficult to distinguish between blood viral particles adhering to the tissue and viral RNA contained within the tissue. Because hepatitis C virus has a single-stranded RNA of positive polarity, a minus-strand RNA is expected to be found in hepatitis C virus-replicating tissues as a template for the synthesis of genomic RNA. To see whether the detection of the minus strand of hepatitis C virus RNA by polymerase chain reaction can be used for the determination of hepatitis C virus-replicating tissues, we examined the presence of the minus strand of hepatitis C virus RNA in the plasma, peripheral blood mononuclear cells and liver specimens of patients with hepatitis C virus infection. The plus-strand RNA was detected in the plasma, peripheral blood mononuclear cells and the liver specimens, but the minus-strand RNA was only detected in the liver. These results suggest that hepatitis C virus replicates in the liver but not in peripheral blood mononuclear cells. This detection method for the minus strand of hepatitis C virus RNA should be useful for determining hepatitis C virus replication in tissues other than liver tissue. PMID- 1312053 TI - [Estradiol inhibits dopamine mediated behavior in rats--an animal model of sex specific differences in schizophrenia]. AB - We found in a representative sample of 392 first hospital admissions for schizophrenia a higher mean age at onset in females by 3.2 to 3.9 years, whereas the lifetime risk was equal for both sexes. In males the rates of onset show a steep increase reaching the maximum value in the age group 15-24 years, followed then by a steady decrease. Females reach the first peak with a clear delay between 20 and 29 years. After the decrease a second smaller peak is observed consistently in females within the age group 45-49 years and over. After having excluded alternative explanations for this gender differences (for example, diagnosis artefacts, sociocultural factors), we hypothesized that the effect of oestradiol on the dopaminergic system enhances the vulnerability threshold for schizophrenia, which is lowered again during the menopause. Alternatively we assumed that testosterone reduces the vulnerability threshold and thus furthers the earlier onset of schizophrenia in males. We tested these hypotheses in animal models by investigating the effects of the gonadal hormones on haloperidol induced catalepsy and on apomorphine-induced stereotypies in both neonatal and adult rats. Testosterone showed no clear influence on the tested dopamine mediated behaviour. Oestradiol caused a significant reduction on both dopamine agonist and dopamine-antagonist induced behaviour. These effects were stronger in neonatal animals. Since oestradiol caused a 2.8-fold reduction of dopamine receptor affinity for sulpiride, we assumed that the behavioural changes caused by oestradiol were accounted for by a down-regulation of the dopaminergic system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312055 TI - Lack of increase in heterozygous alpha 1-antitrypsin deficiency phenotypes among patients with hepatocellular and bile duct carcinoma. AB - Homozygous alpha 1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous alpha 1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous alpha 1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers. We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. alpha 1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and chi 2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous alpha 1-antitrypsin deficiency. Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus-related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312056 TI - Contribution of no-reflow phenomenon to hepatic injury after ischemia reperfusion: evidence for a role for superoxide anion. AB - Controversy exists as to the role of oxygen-derived free radicals in tissue injury and the no-reflow phenomenon in reperfusion injury after ischemia. In this study using an experimental rat model, left hepatic lobar ischemia followed by reperfusion resulted in an increase of serum glutamic pyruvic transaminase at 30 min with concomitant histological evidence of hepatocellular necrosis at 24 hr. In the in vivo liver microcirculation, reperfusion after ischemia resulted in an initial transient return of blood flow, but stasis of blood flow later developed in the liver sinusoids. Thus a no-reflow phenomenon in the microcirculation was demonstrated. Intravenous administration of a long-acting form of superoxide dismutase (half-life 6 hr, dose 4 or 8 mg/kg) significantly decreased the hepatocellular necrosis and reduced the microcirculatory stasis in the liver sinusoids. These studies established the important contribution of the no-reflow phenomenon in ischemia-reperfusion injury to the liver and the participation of superoxide anions in mediating the no-reflow phenomenon. PMID- 1312057 TI - "Cuts both ways": collagenases, lipocyte activation and polyunsaturated lecithin. PMID- 1312058 TI - Multicentric development of pancreatic intraductal carcinoma through atypical papillary hyperplasia. AB - We report a case of multiple intraductal carcinomas of the pancreas associated with diffuse atypical papillary hyperplasia. A 67-year-old Japanese man with a complaint of epigastric pain was examined by endoscopic retrograde pancreatography, which demonstrated multiple dilated branches of the pancreatic duct in the body and tail of the pancreas. Histologic examination on the resected pancreas showed diffuse atypical papillary hyperplasia in multiple dilated ducts associated with multiple intraductal carcinomas. Histologic features are described and multicentric carcinogenesis through atypical papillary hyperplasia is discussed. PMID- 1312059 TI - Inhibition of release of arachidonic acid, superoxide, and IL-1 from human monocytes by monoclonal anti-HLA class II antibodies: effects at proximal and distal points of inositol phospholipid hydrolysis pathway. AB - Incubation of human elutriator-purified monocytes with anti-HLA-DR or DQ antibody inhibited the release of arachidonic acid induced by serum-treated zymosan (STZ), a phagocytic stimulus that is known to induce inositol phospholipid hydrolysis and Ca2+ influx. However, only anti-HLA-DR antibody partially inhibited STZ induced inositol phospholipid hydrolysis and concanavalin-A-induced Ca2+ influx. Incubation with anti-HLA-DR or -DQ antibody inhibited phorbol ester-induced AA release as well as superoxide production and IL-1 release. Inhibition of monocyte function by anti-class II antibodies was not accompanied by cAMP elevation. Furthermore, addition of exogenous db-cAMP and other agents (forskolin, cholera toxin, or 3-isobutyl-1-methyl-xanthine) that increase cAMP levels through different mechanisms, alone or in combination with anti-HLA antibodies, had no inhibitory effect on factor release. Our results demonstrate that perturbation of class II molecules down-modulates cell activation at more than one point of the signal transduction pathway with dominant inhibition distal to inositol phospholipid hydrolysis. They also suggest that the inhibition by anti-HLA class II antibody is probably not mediated via cAMP elevation. PMID- 1312060 TI - Colchicine and methotrexate reduce leukocyte adherence and emigration in rat mesenteric venules. AB - Colchicine and methotrexate are commonly used in the treatment of gout and rheumatoid arthritis, respectively; however the mechanism(s) of action of these drugs remain(s) unknown. The objective of this study was to determine whether colchicine and methotrexate can modify the adhesion and emigration of leukocytes in postcapillary venules that are exposed to inflammatory mediators such as platelet-activating factor (PAF) and leukotriene B4 (LTB4). The rat mesentery was prepared for in vivo microscopic observation. Venules with internal diameters ranging between 25 and 35 microns were selected for study. Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and the number of adherent (stationary for greater than or equal to 30 sec) and emigrated leukocytes were measured during superfusion of the mesentery with bicarbonate-buffered saline (BBS). Repeat measurements of adhesive and hemodynamic parameters were obtained between 50 and 60 min of superfusion with either 100 nM PAF or 20 nM LTB4 added to the superfusate. In some experiments, 1 microM of either colchicine or methotrexate was added to the superfusate containing either PAF or LTB4. Both PAF and LTB4 caused increases in leukocyte adherence and emigration and reductions in leukocyte rolling velocity and venular shear rate. Colchicine effectively prevented all of the adhesive and hemodynamic alterations induced by both inflammatory mediators, while methotrexate was largely effective in preventing the responses elicited by PAF, but not LTB4. These results indicate that the therapeutic actions of colchicine and methotrexate may result from the ability of these agents to interfere with the adhesion and emigration of leukocytes from postcapillary venules. PMID- 1312061 TI - In situ expression of the IL-1-alpha and TNF-alpha genes by Reed-Sternberg cells in Hodgkin's disease. AB - The histopathologic pattern of tissues involved by Hodgkin's disease (HD) suggests excessive activation of environmental cells by cytokines released by Hodgkin-Reed-Sternberg (HRS) cells, which are considered as the neoplastic component of HD lesions. This hypothesis has been supported by many studies performed in vitro using HD cell lines. In this study, we have tried to demonstrate the cytokine-producing cells in an environment as close as possible to the in vivo conditions, using in situ hybridization onto frozen sections of HD samples. [35S]-labelled single-stranded RNA probes were prepared by transcribing human cDNA fragments of the TNF-alpha and IL-1 alpha genes subcloned into appropriate vectors. A total of 19 specimens of HD lesions, including 7 cases of nodular sclerosing (NS) type and 12 cases of mixed cellularity (MC), were tested with both types of probes. Clinical stages included stage I (6 cases), stage II (4 cases), stage III (6 cases) and stage IV (3 cases). TNF-alpha and/or IL-1 alpha expression was observed in 12 among 19 HD cases. However, neither the histological type nor the clinical status of the patients was correlated with the profile of cytokine secretion. Most of the cytokine-producing cells could be identified as HRS cells due to their morphological appearance. In 3 cases, simultaneous analysis by immunohistochemistry and in situ hybridization showed that IL-1 alpha/TNF-alpha mRNA-producing cells simultaneously expressed the CD30 antigen, thereby confirming the HRS nature of these cells. PMID- 1312062 TI - Prevalence of human papillomavirus types 16 and 18 in squamous-cell carcinoma of the penis: a retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction. AB - Human papillomaviruses (HPV), particularly types 16 and 18, may be carcinogenic effectors in a variety of human lower-genital-tract malignancies. Using the highly sensitive technique of differential polymerase chain reaction (D-PCR) with amplimers from the E6 open reading frames of HPV types 16 and 18, a retrospective analysis of a 20-year institutional experience with squamous-cell carcinoma of the penis (SCCP) was performed to determine the prevalence of these HPV types in this malignancy. Paraffin-embedded surgical specimens of primary (N = 27), locally recurrent (N = 5), and metastatic deposits (N = 26) from 29 patients with invasive SCCP were analyzed, as well as primary (N = 3) and recurrent (N = 2) specimens from 2 patients with penile carcinoma in situ (CIS) (Bowen's disease). Nine of the 29 (31%) patients had invasive SCCP containing HPV 16 or 18 DNA, with HPV 16 found in 8 (28%) and HPV 18 in I (3%); no patient had both. In 7 patients in which only tissue from metastatic sites was available, 2 had HPV 16 detected in 2 separate metastatic sites each. Specimens from both primary and metastatic sites were available in an additional 6 patients, and HPV 16 was detected in specimens from 3 of these 6 patients. HPV was detected in comparable copy number at both sites in each patient, indicating that HPV DNA may be a stable component within cancer cells during disease progression. Of patients with CIS only, 1 of 2 was positive for HPV 16, and upon multifocal recurrence, showed persistence of the virus at 2 separate sites. Southern blotting was performed to confirm the presence of type-specific HPV DNA and showed complete concordance with D-PCR, but discordant hybridization intensities for HPV 18 were noted between the control and positive patient specimens; sequence analysis of the patient specimen revealed 4 point mutations in the HPV-18 target segment. Comparison of the HPV positive (both HPV 16 and HPV 18) and HPV-negative groups revealed no statistical differences between groups in patients age or ethnic origin, tumor histologic grade, or incidence of nodal involvement. Kaplan-Meier analysis of both overall and cause-specific survival likewise was not different between groups. These data, particularly the presence of HPV in metastatic deposits, provide strong evidence for an etiologic role of HPV type 16 (and possibly 18) in a substantial sub-set of patients from the southeastern United States who developed SCCP. PMID- 1312063 TI - Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice. AB - Topoisomerase (topo) I and II are nuclear enzymes which are novel targets of cancer chemotherapy. A new camptothecin (CPT) analog, 7-ethyl-10-[4-(1 piperidino)-1-piperidino]carbonyl-oxy-CPT (CPT-11), is a topo-I inhibitor with a higher activity and less toxicity than CPT. To investigate topo-I and -II targeting chemotherapy in an in vivo model, we studied the effect of sequential or co-treatment using CPT-11 and adriamycin (ADR) a topo-II inhibitor, in 6 human tumor xenografts (2 esophageal, 2 gastric and 2 colon tumor lines). In sequential treatment, adriamycin was administered i.v. 24 hr after CPT-11 treatment, and no antagonistic effect of this treatment schedule was observed. ADR cytotoxicity was potentiated significantly by CPT-11 pretreatment in the case of 2 esophageal and 2 gastric tumor lines and 1 colon tumor line. On the other hand, co-treatment abolished the sensitivity to CPT-11 and ADR in all 6 tumor lines. Moreover, CPT 11 did not significantly enhance the cytotoxicity of other agents tested, including mitomycin C (MMC) and cisplatin (CDDP). Flow cytometry and dot-blot analyses showed that CPT-11 pretreatment induced an increase in the S-phase cell population with an increase of topo-II mRNA expression after 24 and 48 hr, respectively, in the esophageal and colon tumor lines. These results suggest that CPT-11 can modulate topo-11 levels to enhance the effect of topo-II inhibitors in some human tumors, and this suggests a new clinical method of topo-I and -II targeting chemotherapy for human solid tumors. PMID- 1312064 TI - Visualization of the plasmin receptor on carcinoma cells. AB - In order to visualize the receptor for plasmin and plasminogen present on human carcinoma cells, SW1116 and MCF7-MF cells were incubated with biotinylated plasminogen or plasmin and fluoresceinated streptavidin, and counterstained with propidium iodide. It was first demonstrated that biotinylation did not alter the binding properties of plasminogen and plasmin, provided that the biotinylation rate was around 2. Specific staining of tumor cells was obtained using these reagents. Images with green fluorescence were clearly visible as grains or contours at the surface of tumor cells. The localization of fluorescent grains was analyzed more precisely using confocal microscopy. The percentage of stained cells varied from one experiment to another between 10 and 60%. In no experiment were all the cells observed to be positive. Mitotic cells were more frequently stained than non-mitotic cells, suggesting a relationship between the presence of plasmin receptors and cell proliferation. This was confirmed by the use of Ki67 monoclonal antibody (MAb), as B-Pg-binding tumor cells generally had their nucleus stained by this antibody. Other images indicated staining of the extracellular matrix. Finally, 2 rat tumor-cell sub-lines of colonic origin (DHD K12 Pro-b and Reg-b) were shown to bind human biotinylated plasminogen, confirming the strong interspecies reactivity of plasmin receptors. PMID- 1312065 TI - Effect of TGF-beta 1 on the EBV-induced transformation of human lymphocyte cultures. AB - We tested the effect of TGF-beta 1 on the EBV-induced activation and immortalization of human B lymphocytes. In lymphocyte cultures of EBV seropositive individuals, T cells can inhibit the EBV-induced transformation of B cells. We found that in the presence of TGF-beta 1 the transformation was more efficient, due to the inhibition of this function. TGF-beta 1 inhibited the EBV induced proliferation of purified B-cell cultures. Its effect was strongest when added at the beginning of the culture. Added later, the inhibition gradually decreased and was lost by the 4th day. After 10 to 14 days, in the cultures initiated with TGF-beta 1, the number of cells was higher and they formed larger aggregates as compared with control cultures. Thus, TGF-beta 1 modifies EBV induced transformation in a complex way. It inhibits the activation of B cells but does not affect those already activated. Once they acquire the immortalized state, the B cells are even stimulated by TGF-beta 1. PMID- 1312066 TI - Detection of simian T-lymphotropic virus type I using the polymerase chain reaction. AB - To develop the polymerase chain reaction (PCR) for the detection of simian T lymphotropic virus type I (STLV-I) infection, cell lines or peripheral-blood mononuclear cells (PBMC) from 2 non-human primate species [African green monkeys (AGM), Cercopithecus aethiops; baboon, Papio cynocephalus] were evaluated for their STLV-I status using oligonucleotide primer pairs and probes specific for the tax and pol gene regions of the closely related human T-lymphotropic virus type I (HTLV-I). These PCR results were compared with serologic (Western blot assay) and viral culture (p24-antigen capture assay) data. PCR products for both gene regions were detected in established baboon, Japanese macaque and rhesus macaque STLV-I-producing cell lines. STLV-I tax and pol products were also detected in PBMC from 4 of 4 infected AGM and 4 of 4 infected baboons, each of which were also Western-blot-positive and p24-antigen-capture-positive. Of the remaining AGM (n = 7) and baboon (n = 1) which were PCR-negative, each was also Western-blot-negative and p24-antigen-capture-negative. Two seronegative and virus-culture-negative AGM were classified as PCR indeterminate with weak reactivity using tax primers. These primer pairs failed to amplify DNA from uninfected human PBMC, an uninfected human lymphoid cell line, a simian immunodeficiency virus macaque (SIVmac251)-infected cell line and a simian retrovirus-type-D(SRV-D)-infected cell line. HTLV-II-pol-specific primer pairs failed to amplify DNA from STLV-I-infected cell lines and PBMC from STLV-I infected monkeys. Further, HTLV-I pol and tax primer pairs successfully amplified RNA from HTLV-I- and STLV-I-infected cell lines by reverse transcriptase (RT) PCR. We have demonstrated excellent specificity in the detection of STLV-I by PCR using these HTLV-I-derived primers and probes. Additionally, our data suggest that the tax and pol gene regions are conserved between HTLV-I and STLV-I strains found among these diverse species of non-human primates. PMID- 1312067 TI - TGF-beta stimulation of endometrial and breast-cancer cell growth. AB - Growth of the human endometrial carcinoma Ishikawa cell line was stimulated by transforming growth factor-beta1 when cultured in serum-containing and chemically defined culture medium. This response was not unique to endometrial carcinoma cells, as the breast-cancer cell line, T47-D, was similarly stimulated by TGF beta 1. TGF-beta 1 stimulated growth of MCF-7 breast-cancer cells in chemically defined medium but inhibited growth of this cell line in serum-containing medium. The data provide a demonstration of a positive growth response to TGF-beta 1 in oestrogen-receptor-positive cells and do not support the hypothesis that this growth factor is simply a negative growth regulator in epithelial-cancer cell lines. PMID- 1312068 TI - Antibody to hepatitis C virus in selected groups of a Canadian urban population. AB - In an anonymous survey, 433 sera from Canadian individuals of selected categories were tested for the presence of antibody to hepatitis C virus (HCV) using a recombinant antigen-based immunoassay. About 50% of intravenous drug abusers (IVDA), 10% of transfusion recipients and an overall average of 7.9% of male homosexuals were reactive for antibody to HCV. Individuals with jaundice and negative hepatitis B virus (HBV) serology were not reactive for antibody to HCV compared with 26.7% of those with positive HBV serology. Similarly 58% of male Federal prisoners with positive HBV serology were also HCV-antibody reactive compared with 15% of those with negative HBV serology. A prevalence of 1.2% was recorded for individuals not in any of the above groups. Of 433 sera, 92 were reactive and the discrimination in absorbance values between reactive and not reactive samples was good except for 13 sera, eight of which gave values considerably higher than the average negative value and five which were just above the positive threshold. PMID- 1312069 TI - Effect of copper ion on collagenase release. Its implication in corneal vascularization. AB - The involvement of leukocytes in corneal neovascularization has been known for a long time. Recent observations suggest that collagenase from leukocytes may be a common mediator for prostaglandin E1 (PGE1)- and copper-induced corneal neovascularization. This study was designed to investigate the effect of copper ion on collagenase activity from leukocytes and other sources and leukocyte infiltration in the corneal angiogenic process induced by PGE1. These results demonstrated that collagenase production from leukocytes was stimulated in a dose dependent manner by copper ion but not by PGE1. Copper chloride 0.2 mM produced the highest stimulation. Copper ion had no effect on collagenase release from corneal fibroblasts and capillary endothelium. There were more polymorphonuclear leukocytes (PMN) in the prostaglandin E1 treated corneas than in the control. The time-course study showed that the appearance of PMN reached a peak on day 2 and new vessel growth could not be identified until day 4. These results supported an earlier suggestion that leukocytes play a role in corneal neovascularization and further suggested that copper in corneal neovascularization can stimulate the release of collagenase from leukocytes. PMID- 1312071 TI - Identification and partial characterization of TGF-beta 1 receptors on trabecular cells. AB - By using two specific receptor assays, we identified and partially characterized receptors for transforming growth factor-beta 1 (TGF-beta 1) on porcine trabecular cells in vitro. Cultured trabecular cells were incubated with labeled TGF-beta 1 and analyzed by flow cytometry. Pretreatment with trypsin or preincubation with cold TGF-beta 1 or a neutralizing antibody to TGF-beta 1 inhibited the binding of labeled TGF-beta 1. 125I-TGF-beta 1 was cross-linked covalently to cell surface receptors on the trabecular cells. By SDS-PAGE and autoradiography, we identified three labeled macromolecular species of receptors, two of which had apparent molecular weights greater than 212 kDa and one of which had an apparent molecular weight of approximately 80-90 kDa under reducing conditions. The low and high molecular weight species probably represent type II and type III TGF-beta 1 receptors, respectively. At concentrations of 0.5 and 1 ng/ml, activated TGF-beta 1 caused retraction and a marked decrease in the rate of proliferation and in the motility of trabecular cells in vitro. Our findings implicate TGF-beta 1 in the modulation of the functional homeostasis of trabecular cells and suggest that the aqueous humor contains a level of TGF-beta 1 which, once activated, is sufficient to exert a biologic effect on the trabecular meshwork. PMID- 1312070 TI - An ocular model of adenovirus type 5 infection in the NZ rabbit. AB - Ocular adenoviral infections occur worldwide, and currently, there is no ocular animal model for evaluating new antivirals or studying pathogenesis. With a paired-eye design, an ocular model was developed in 32 New Zealand rabbits following topical and intrastromal inoculation with a clinical isolate of adenovirus type 5 (Ad5 McEwen). Clinical signs of infection--conjunctivitis, corneal edema, subepithelial infiltrates, and iritis--and seroconversion were evaluated. Replicating virus on the ocular surface was determined by serial ocular titers. Reproducible acute ocular infection was demonstrated in 32 of 32 infected eyes (100%), with mean viral replication lasting for 8.3 days. Peak ocular viral titers (10(3) plaque forming units/ml) were achieved on day three after inoculation and represented a 2 log increase (100 times) over day one. Ocular viral replication was associated with acute conjunctivitis (24/34 eyes, 75%), and delayed-onset presumed immune-mediated clinical disease was associated with: blepharoconjunctivitis (21/32 eyes, 66%), iritis (29/32 eyes, 91%), corneal edema (32/32 eyes, 100%), and subepithelial corneal infiltrates (30/32 eyes, 94%). Seroconversion was demonstrated in 26 of 31 rabbits (84%). The study concludes that a potentially useful animal model of adenoviral ocular infection can be attained. PMID- 1312072 TI - Prolactin localization, binding, and effects on peroxidase release in rat exorbital lacrimal gland. AB - Prolactin immunoreactivity has been detected in human tears and in lacrimal glands, and it has been suggested that this hormone might be a modulator of lacrimal secretion as well as a component of lacrimal gland fluid. The present study was designed to confirm the immunocytochemical localization of prolactin in the rat lacrimal gland, to determine the source of the prolactin, and to evaluate the acute effects of prolactin on lacrimal secretory function. We have confirmed that prolactin-like immunoreactivity is present in secretory vesicles of acinar cells of male and female Sprague-Dawley rats. Prolactin message was present at detectable levels in RNA extracts of lacrimal glands from males, indicating that at least a component of the prolactin-like immunoreactivity was the product of synthesis within the lacrimal glands. Crude membrane fractions from acini isolated from males bound 43.1 +/- 3.2 femtomoles prolactin/mg protein (mean +/- standard error of the mean; n = 6), which was significantly (P less than 0.01) more than comparable fractions from females (15.4 +/- 2.4 fmoles/mg protein, n = 6). Preincubating membranes at 65 degrees for 20 min to release endogenous ligands increased prolactin binding to 84.8 +/- 20.8 fmoles/mg protein for males and 63.8 +/- 17.4 fmoles/mg protein for females (P greater than 0.1), suggesting that, on average, similar numbers of receptors are expressed in acinar cells of male and female rats but a larger fraction of the receptors is occupied by endogenous prolactin-like peptides in females. Because prolactin binding triggers prolactin receptor internalization in various cell types, we propose that the prolactin-like immunoreactivity in lacrimal acinar cells of females has been accumulated from the circulation, while the immunoreactivity seen in males results, at least in part, from de novo synthesis. Ovine prolactin at concentrations of 10-20 ng/ml inhibited carbachol-induced peroxidase release by 19.6% +/- 6.9% (n = 8, P less than 0.02) but failed to alter peroxidase release in the absence of carbachol. These observations suggest that prolactin might function as an endocrine, paracrine, or autocrine modulator in the lacrimal gland. PMID- 1312073 TI - The importance of peroxide and superoxide in the X-ray response. AB - Radiation produces a number of damaging radicals as well as peroxide. The chief cellular protection against these radicals, their secondary reactants and peroxide is the cellular glutathione (GSH), GSH peroxidase, GSH-S-transferase (GSHTase), and catalase enzymes. Inhibition of cellular catalase alone does not enhance the aerobic radiation response because cellular GSH peroxidase is equally effective in reducing peroxide. However, inhibition of GSHTase, and partial inhibition of peroxidase by L-buthionine sulfoximine (LBSO)-linked GSH depletion, results in an increased aerobic radiation response. The major pathway for peroxide reduction is the GSH peroxidase. The enzyme is accountable for 70% inactivation of low peroxide concentrations. Catalase accounts for the remaining inactivation. However, it is difficult to assess the relative contributions of GSHTase and peroxidase to the inactivation of radiation-produced hydroperoxides. Our data suggest that GSH depletion results in the inhibition of cellular GSHTase before it inhibits GSH peroxidase. Therefore, part of the increased aerobic radiation response maybe due to cellular inability to reduce hydroperoxides. Peroxide is not a substrate for GSHTase. However, total inhibition of peroxidase by L-BSO plus N-ethylmaleimide (NEM) treatment maximizes the aerobic radiation response. Total inhibition of GSH-S-transferase and peroxidase would block both peroxide and hydroperoxide reduction. PMID- 1312074 TI - Magnetic resonance spectroscopic measurement of cellular thiol reduction oxidation state. AB - Chromatographic and magnetic resonance spectroscopic measurements of thiol reduction-oxidation state in chemically constructed samples show close analytical agreement. This result, coupled with the synthesis of new probe molecules allowing greater sensitivity and lower toxicity, supports the development of an NMR method for non-invasive thiol redox measurement, an important variable in the response of tumors to radiation and chemotherapy. PMID- 1312075 TI - Protection by WR-2721 of the toxicity induced by the combination of cisplatin and 5-fluorouracil. AB - We evaluated the effects of WR-2721 and its metabolite WR-1065 on in vitro growth inhibition by 5-fluorouracil (5FU) and cisplatin (CDDP) and the effect of WR-2721 on in vivo toxicity and antitumor effect of 5FU and CDDP. In cell culture both WR 2721 and WR-1065 were not able to reverse growth inhibition caused by either 5FU or CDDP. Administration of WR-2721 i.p. at 525 mg/kg to mice resulted in a severe temperature drop to 27 degrees C; at 200 mg/kg hypothermia was less severe. WR 2721 failed to prevent 5FU toxicity, but the maximum tolerated dose of CDDP in the combination with 5FU (at 100 mg/kg) could be increased from 3 to 7 mg/kg. CDDP at 7 mg/kg enhanced leukopenia caused by 5FU at 100 mg/kg to 20% and thrombocytopenia to 40%; WR-2721 reduced leukopenia and prevented thrombocytopenia induced by the combination. Combination of CDDP, 5FU, and WR 2721 resulted in an enhanced antitumor activity against the murine colon tumor Colon 26 compared to 5FU alone and to 5FU combined with CDDP at their maximum tolerated dose. PMID- 1312076 TI - A phase I study of WR-2721 in combination with total body irradiation (TBI) in patients with refractory lymphoid malignancies. AB - This Phase I study was designed to establish the maximum tolerated dose (MTD) of WR-2721 when given twice weekly with total body irradiation (TBI) in the treatment of patients with advanced refractory lymphoid malignancies and to define the toxicities of this combination and schedule. Patients eligible for this study had advanced recurrent indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Patients had symptomatic or progressive disease, a performance status of 0, 1, or 2, and adequate bone marrow, hepatic, and renal function. Only patients failing one or two regimens of prior chemotherapy were eligible. Patients who had received prior extended field irradiation were ineligible. Patients received TBI twice weekly (Tuesday and Friday) to a total of 10 doses at 15 cGy/fx. WR-2721 was given intravenously over 15 min beginning 30 min before irradiation. The escalation of WR-2721 was Level 1: 740 mg/m2 and Level 2: 910 mg/m2. The MTD of WR-2721 was that dose which produced predictable and reversible toxicity and would not interfere with patient well-being. Seven patients were entered onto the study, three at 740 mg/m2 and four at 910 mg/m2. Five patients had CLL and two patients small lymphocytic NHL. No patient had hypotension or nausea requiring reduction in dose level or even interruption of infusion of WR-2721. At 740 mg/m2 no grade 3 or 4 toxicities related to WR-2721 were observed, but two patients could not complete treatment because of TBI-induced prolonged thrombocytopenia following treatments 5 and 8. One patient completed all 10 treatments. At 910 mg/m2 of WR-2721, two patients requested removal from study because of malaise, one after 5 cycles and one after 7 cycles. One patient completed all 10 treatments. One patient was treated with a modified schedule of 7 treatments of 20 cGy/fx and tolerated and completed all treatments but developed significant thrombocytopenia following completion of treatment. No patients had disease progression during treatment. The median survival was 11 months. This study indicates that WR-2721 given at 910 mg/m2 twice weekly with TBI is well tolerated for at least 5 treatments and that 910 mg/m2 of WR-2721 is the MTD with this regimen. In view of the importance of total radiation dose in achieving a response with TBI, a dose escalation study of TBI with 910 mg/m2 of WR-2721 should be performed in patients with indolent non Hodgkin's lymphoma. PMID- 1312077 TI - Modification of radiation-induced carcinogenesis in mice by misonidazole and WR 2721. AB - The effects of the radiosensitizer misonidazole (MISO) and the radioprotector WR 2721 on radiation-induced carcinogenesis in C3Hf/Kam mice were investigated. The right hind legs were exposed to graded single doses of gamma-rays. MISO and WR 2721 were given i.p. 30 min before irradiation at a dose of 1 mg/g and 0.4 mg/g, respectively. The RCD50, or radiation dose inducing tumors in 50% of the irradiated legs, was determined 650 days after treatment. The same animals were also checked for the effect of these drugs on hair loss and radiation-induced leg contractures. MISO enhanced radiation carcinogenesis by a factor of 1.43, whereas WR-2721 reduced it by a factor of 1.75. These effects on carcinogenesis correlated well with the modifying effects of the two agents on radiation-induced hair loss (early damage) and leg contractures (late damage). PMID- 1312078 TI - Interim analysis of a randomized trial of radiation therapy of rectal cancer with/without WR-2721. AB - The objectives of this randomized trial are to define the maximum tolerated dose of radiation therapy, at curative dose levels, that can be delivered following WR 2721, and to observe the anti-tumor effects and normal tissue responses. One hundred patients with inoperable, unresectable, or recurrent rectal cancer were stratified and randomized to radiation only, or WR-2721 and radiation. The entire pelvis is treated with 4 portals 4 times a week to a total of 4500 cGy (first level dose) in 5 weeks. WR-2721, 340 mg/m2 was given 15 minutes before radiation to the combination group. Subsequently, both groups received a conedown of 720 cGy in 4 days to 144(2) cm portals APPA, and if originally inoperable or unresectable 720 cGy in four days to second conedown of 64(2) cm. Patients were observed from 3 to 18 months (median = 12 months). No significant hypotension or hematologic toxicity occurred in the WR-2721 treated group. Mild to moderate emesis occurred in 80% of the courses. (No antiemetics were used.) Moderate or severe acute toxicities to normal tissues were observed less frequently in the WR 2721 arm. No moderate or severe late toxicities to the skin, mucous membrane, urinary bladder or intestine was observed in the WR-2721 group, however, 5 patients treated with radiation alone experienced moderate or severe late toxicity to these organs. No evidence of tumor protection was observed. PMID- 1312079 TI - mRNA levels of catalytic subunits of protein phosphatases 1, 2A, and 2C in hepatocarcinogenesis. AB - The mRNA levels of three phosphoseryl/phosphothreonyl protein phosphatases, PP1, PP2A and PP2C, in rat liver have been determined by Northern blot analysis in various stages of rat chemical hepatocarcinogenesis using a Solt-Farber model. Five weeks after administration of diethylnitrosamine, the mRNA levels of PP1 alpha, PP2A and PP2C were elevated 8, 29 and 11 times, respectively, as compared to those of the control livers. However, in primary hepatoma induced according to the Solt-Farber model, the mRNA levels of all three protein phosphatases were dramatically decreased to normal levels or even to much lower levels, whereas the mRNA level of glutathione S-transferase placental form, a tumor marker protein, was greatly elevated as compared with that of the control livers. In a poorly differentiated hepatoma AH13, a line of rat ascites hepatoma, the mRNA level of PP1 alpha was 5.6 times higher than that of the control livers, whereas the mRNA lever of PP2C was almost the same as that of the control livers and the level of PP2A mRNA was distinctly lower than that of the control livers. These data appear to suggest some involvement of protein phosphatases in hepatocarcinogenesis. PMID- 1312080 TI - Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas. AB - The expressions of transforming growth factor beta (TGF-beta) and its receptor and TGF-beta inhibitory element (TIE)-binding protein were examined on human gastric carcinomas by Northern blot hybridization, immunohistochemistry, affinity labeling and gel retardation analysis. TGF-beta mRNA was expressed in tumor and normal tissues at various levels. Immunohistochemically, TGF-beta expression was confirmed to be present within tumor cells. Out of the 17 human gastric carcinoma tissues, 14 (82%) showed a reduction in the level of type I receptor (65 kDa) for TGF-beta when compared to corresponding normal mucosas. Interestingly, in seven of the 14 tumors the level of TIE-binding protein in the tumor tissue was lower than that in normal mucosa. Human gastric carcinoma cell line TMK-1, whose growth was inhibited by TGF-beta, had only type I receptor for TGF-beta and showed a high level of TIE-binding protein. Conversely, MKN-1, a TGF-beta-resistant cell line, exhibited an extremely low level of TGF-beta receptor and had no TIE binding protein. These results overall indicate that although human gastric carcinoma cells produced TGF-beta, they showed a reduction in TGF-beta type I receptor and a low level of TIE-binding protein, resulting in escape from growth inhibition by TGF-beta. PMID- 1312081 TI - Insulin induces translocation of the alpha 2 and beta 1 subunits of the Na+/K(+) ATPase from intracellular compartments to the plasma membrane in mammalian skeletal muscle. AB - Unlike glucose transport, where translocation of the insulin-responsive glucose transporter (GLUT4) from an intracellular compartment to the plasma membrane is the principal mechanism underlying insulin stimulation, no consensus exists presently for the mechanism by which insulin activates the Na+/K(+)-ATPase. We have investigated (i) the subunit isoforms expressed and (ii) the effect of insulin on the subcellular distribution of the alpha beta isoforms of the Na+/K(+)-ATPase in plasma membranes (PM) and internal membranes (IM) from rat skeletal muscle. Western blot analysis, using isoform-specific antibodies to the various subunits of the Na+/K(+)-ATPase, revealed that skeletal muscle PM contains the alpha 1 and alpha 2 catalytic subunits and the beta 1 and beta 2 subunits of the Na+ pump. Skeletal muscle IM were enriched in alpha 2, beta 1, and beta 2; alpha 1 was barely detectable in this fraction. After insulin treatment, alpha 2 content in the PM increased, with a parallel decrease in its abundance in the IM pool; insulin did not have any effect on alpha 1 isoform amount or subcellular distribution. The beta 1 subunit, but not beta 2, was also elevated in the PM after insulin treatment, but this increase originated from a sucrose gradient fraction different from that of the alpha 2 subunit. Our findings suggest that insulin induces an isoform-specific translocation of Na+ pump subunits from different intracellular sources to the PM and that the hormone responsive enzyme in rat skeletal muscle is an alpha 2:beta 1 dimer. PMID- 1312082 TI - Ceramide stimulates a cytosolic protein phosphatase. AB - A sphingomyelin cycle has been identified whereby the action of certain extracellular agents results in reversible sphingomyelin hydrolysis and the concomitant generation of ceramide. Moreover, a cell-permeable ceramide, C2 ceramide (N-acetylsphingosine), is a potent modulator of cell proliferation and differentiation. We report herein that C2-ceramide, C6-ceramide, and natural ceramides activate a cytosolic serine/threonine protein phosphatase in a dose dependent manner. Initial activation is observed at concentrations of ceramide as low as 0.1 microM with peak response occurring at 5-10 microM. However, other closely related sphingolipids, sphingosine and sphingomyelin, were largely inactive. Ceramide-stimulated phosphatase was inhibited by okadaic acid, an inhibitor of protein phosphatases, with an IC50 of 0.1-1 nM, depending on the concentration of ceramide. Ceramide-stimulated phosphatase was insensitive to Mg2+ and Mn2+ cations. Using sequential anion exchange chromatography, ceramide stimulated phosphatase activity could be resolved from ceramide-nonresponsive phosphatases. The activity of partially purified enzyme was stimulated 3.5-fold by ceramide. The identification of a phosphatase as a molecular target for the action of ceramide defines a novel intracellular signaling pathway with potential roles in the regulation of cell proliferation and differentiation. PMID- 1312083 TI - Regulation of neutrophil superoxide by antichymotrypsin-chymotrypsin complexes. AB - The ability of neutrophils to generate free radicals is a crucial component of host defense (Babior, B. M. (1978) N. Engl. J. Med. 298, 659-668, 721-725. Neutrophil oxidants, however, can cause significant host tissue destruction (Weiss, S. J. (1989) N. Engl. J. Med. 320, 365-376), and the regulation of free radical production is not well understood. We have previously shown that recombinant antichymotrypsin (rACT), a serine protease inhibitor, inhibits superoxide production in intact neutrophils (Kilpatrick, L., Johnson, J. L., Nickbarg, E. B., Wang, Z., Clifford, T. F., Banach, M., Cooperman, B. S., Douglas, S. D., and Rubin, H. (1991) J. Immunol. 146, 2388-2393). Using a cell free NADPH oxidase preparation, we now demonstrate that rACT alone has no effect on superoxide production and that antichymotrypsin-chymotrypsin (rACT.CT) complexes are required to inhibit superoxide, suggesting that neutrophil chymotrypsin-like proteases produce conformational changes in ACT, allowing it to become active in regulating superoxide production. Additionally, we have identified NADPH oxidase itself as the target for rACT.CT and have demonstrated that rACT.CT interferes specifically with activation of the NADPH oxidase without changing the Km for NADPH or the rate constant describing the rate-limiting step in activation. These observations suggest an important role for antichymotrypsin in the regulation of NADPH-oxidase activation, which is a prerequisite for neutrophil superoxide production, and predict possible therapeutic uses for rACT in conditions where unregulated neutrophil-free radical production has been implicated in the mechanism of tissue destruction. PMID- 1312084 TI - A differential location of phosphoinositide kinases, diacylglycerol kinase, and phospholipase C in the nuclear matrix. AB - Several enzymes involved in the phosphoinositide metabolism have been shown to be present in nuclei of rat liver and Friend cells. In this paper we demonstrate that nuclear matrices of mouse NIH 3T3-fibroblasts and rat liver cells, isolated by nuclease treatment and high salt extraction, contain phosphatidylinositol 4 kinase (PdtIns 4-kinase), phosphatidylinositol 4-phosphate 5-kinase (PtdIns(4)P 5 kinase), diacylglycerol kinase, and phospholipase C. By a selective extraction the nucleus can be dissected in the peripheral matrix (lamina-pore complex) and the internal matrix as shown by using marker antibodies. Surprisingly, PtdIns 4 kinase was found exclusively in the peripheral nuclear matrix, whereas PtdIns(4)P 5-kinase was found to be associated to internal matrix structures. Diacylglycerol kinase and phospholipase C activities were also preferentially detected in the internal matrix. These data demonstrate a differential localization of the phosphoinositide kinases in the nucleus and suggest that the phosphoinositide metabolism may play a specific role in the nucleus. PMID- 1312085 TI - The 38-amino acid form of pituitary adenylate cyclase-activating polypeptide stimulates dual signaling cascades in PC12 cells and promotes neurite outgrowth. AB - Vasoactive intestinal peptide (VIP) activates adenylylcyclase in sympathoadrenal cells at concentrations greater than 10(-6) M. We demonstrate here that two forms of a newly discovered peptide with homology to VIP named pituitary adenylate cyclase-activating polypeptide (PACAP) are much more potent activators of signal transduction in PC12 cells. Both the 27- and 38-amino acid forms of PACAP elevate cAMP levels in PC12 cells and stimulate adenylylcyclase in PC12 membranes, with an EC50 near 10(-9) M. PACAP38 additionally is a potent activator of the inositol lipid cascade in PC12 cells, elevating the content of inositol phosphates by 8 fold at 10(-8) M (EC50 = 7 x 10(-9) M). PACAP38 and PACAP27 have been thought to have essentially identical actions, but PACAP27 is 2-3 logs less potent in increasing inositol lipid levels. Moreover, PACAP38 at 10(-8) M is an effective inducer of neuronal morphology in PC12 cells, whereas PACAP27 is much less active in promoting neurite outgrowth. In contrast to the PACAP-preferring receptors on PC12 cells, another class of PACAP-binding sites with equal high affinities for VIP, PACAP38, and PACAP27 has been identified on several other cell types. We find that the cAMP content of rat CH3 pituitary cells, known to have high affinity VIP receptors, is in fact potently elevated by PACAP27 and PACAP38 as well as by VIP. However, PACAP38, even at 10(-6) M, is not capable of significant activation of inositol lipid turnover via these VIP/PACAP nondiscriminating sites. PMID- 1312086 TI - Delivery of ion pumps from exogenous membrane-rich sources into mammalian red blood cells. AB - Using polyethylene glycol-mediated fusion of ATP-ase-enriched (native) microsomes with red blood cells, we have delivered sarcoplasmic reticulum (SR) Ca-ATPase and kidney Na,K-ATPase into the mammalian erythrocyte membrane. Experiments involving delivery of the SR Ca-ATPase into human red cells were first carried out to assess the feasibility of the fusion protocol. Whereas there was little detectable 45Ca2+ uptake into control cells in either the absence or presence of extracellular ATP, a marked time-dependent uptake of 45Ca2+ was observed in the presence of ATP in cells fused with SR Ca-ATPase. Comparison of the kinetics of uptake into microsome-fused cells versus native SR vesicles supports the conclusion of true delivery of pumps into the red cell membrane. Thus, the time to reach steady state was more than two orders of magnitude longer in the (large) cells versus the native SR vesicles. Na,K-ATPase from dog and rat kidney microsomes were fused with red cells of humans, sheep, and dogs. Using dog kidney microsomes fused with dog red cells which are practically devoid of Na,K-ATPase, functional incorporation of sodium pumps was evidenced in ouabain-sensitive Rb+ uptake and Na+ efflux energized by intracellular ATP, as well as in ATP stimulated Na+ influx and Rb+ efflux from inside-out membrane vesicles prepared from the fusion-treated cells. From analysis of the biphasic kinetics of ouabain sensitive Na+ efflux under conditions of limited intracellular Na+ concentration, it is concluded that the kidney pumps are incorporated into a relatively small fraction (approximately 15%) of the red cells. This system provides a uniquely useful system for studying the behavior of native sodium pumps in a compartment (red cell) of small surface/volume ratio. The newly incorporated native kidney pumps, while of the same isoform as the endogenous red cell pump, behave differently from the endogenous red cell sodium pump with respect to their very low "uncoupled" Na+/O flux activity. PMID- 1312087 TI - Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. AB - Structural mitochondrial damage accompanies the cytotoxic effects of several drugs including tumor necrosis factor (TNF). Using various inhibitors of mitochondrial electron transport we have investigated the mechanism of TNF mediated cytotoxicity in L929 and WEHI 164 clone 13 mouse fibrosarcoma cells. Inhibitors with different sites of action modulated TNF cytotoxicity, however, with contrasting effects on final cell viability. Inhibition of mitochondrial electron transport at complex III (cytochrome c reductase) by antimycin A resulted in a marked potentiation of TNF-mediated injury. In contrast, when the electron flow to ubiquinone was blocked, either at complex I (NADH-ubiquinone oxidoreductase) with amytal or at complex II (succinate-ubiquinone reductase) with thenoyltrifluoroacetone, cells were markedly protected against TNF cytotoxicity. Neither uncouplers nor inhibitors of oxidative phosphorylation nor complex IV (cytochrome c oxidase) inhibitors significantly interfered with TNF mediated effects, ruling out the involvement of energy-coupled phenomena. In addition, the toxic effects of TNF were counteracted by the addition of antioxidants and iron chelators. Furthermore, we analyzed the direct effect of TNF on mitochondrial morphology and functions. Treatment of L929 cells with TNF led to an early degeneration of the mitochondrial ultrastructure without any pronounced damage of other cellular organelles. Analysis of the mitochondrial electron flow revealed that TNF treatment led to a rapid inhibition of the mitochondria to oxidize succinate and NADH-linked substrates. The inhibition of electron transport was dose-dependent and became readily detectable 60 min after the start of TNF treatment, thus preceding the onset of cell death by at least 3 6 h. In contrast, only minor effects were observed on complex IV activity. The different effects observed with the mitochondrial respiratory chain inhibitors provide suggestive evidence that mitochondrial production of oxygen radicals mainly generated at the ubisemiquinone site is a causal mechanism of TNF cytotoxicity. This conclusion is further supported by the protective effect of antioxidants as well as the selective pattern of damage of mitochondrial chain components and characteristic alterations of the mitochondrial ultrastructure. PMID- 1312088 TI - Termination complex in Escherichia coli inhibits SV40 DNA replication in vitro by impeding the action of T antigen helicase. AB - DNA replication terminus (ter)-binding protein (TBP) in Escherichia coli binds specifically to the terminus (ter) site, and the resulting complex severely blocks DNA replication in an unique orientation by inhibiting the action of helicases. To generalize the intrinsic nature of the orientated ter-TBP complex against various helicases, we tested the potential of the complex to inhibit the action of three helicases, DNA helicase I, simian virus 40 (SV40) large tumor (T) antigen, and helicase B, derived from F plasmid, SV40, and mouse FM3A cell, respectively. The complex impeded the unwinding activities of all tested helicases in a specific orientation, with the same polarity observed in case of blockage of a replication fork, and, as a result, there was a block of SV40 DNA replication in both crude and purified enzyme systems in vitro. As the specificity in polarity of inhibition extends to heterologous systems, there may be common structure/mechanism features in helicases. PMID- 1312089 TI - A post-translational modification, unrelated to hydroxylation, in the collagenous domain of nonhelical pro-alpha 2(I) procollagen chains secreted by chemically transformed hamster fibroblasts. AB - Transformed Syrian hamster embryo (NQT-SHE) fibroblasts do not synthesize the pro alpha 1 subunit of type I procollagen, but secrete two modified forms of the pro alpha 2(I) subunit that migrate more slowly than the normal chain during gel electrophoresis (Peterkofsky, B., and Prather, W. (1986) J. Biol. Chem. 261, 16818-16826). By electrophoretic analysis of cyanogen bromide and V8 protease derived peptides from the collagenous domains of intra- and extracellular pro alpha 2(I) chains, we find that the modification occurs almost exclusively in secreted molecules, is located in the region spanned by the cyanogen bromide peptide CB3,5, and persists when hydroxylation is inhibited. Thus, modification is due to a post-translational reaction other than hydroxylation. The modified chains appear to be secreted in the denatured state since: 1) helical structures formed at 4 degrees C under acidic conditions were unstable under neutral conditions at 37 degrees C; 2) conditions that destabilize the type I procollagen helix and thus inhibit its secretion, i.e. inhibition of proline hydroxylation or incorporation of the proline analog cis-hydroxyproline, did not affect secretion of the modified chains. The time courses for secretion of nonhelical modified chains from NQT-SHE and of hydroxylated helical procollagen I from control cells, as a proportion of total collagen synthesized, were similar. Although cis hydroxyproline did not inhibit the secretion of the modified chains, it induced their rapid intracellular degradation. PMID- 1312090 TI - Cloning and disruption of a putative NaH-antiporter gene of Enterococcus hirae. AB - When growing in a sodium-rich environment, wild-type Enterococcus hirae extrudes sodium by two mechanisms, ATP-driven sodium extrusion, and NaH-antiport. Mutant 7683 is unable to grow on sodium-rich media. This is due to two mutations, one inactivating ATP-driven sodium transport and a second rendering NaH-antiport inoperative. 7683 was transformed by electroporation with a gene bank, derived from E. hirae, in an Escherichia coli-E. hirae shuttle vector. Transformants which had regained the ability to grow on sodium-rich media were selected for and the transforming plasmids analyzed. A gene able to restore NaH-antiport activity in 7683 was identified. This gene was named napA. It codes for an extremely hydrophobic protein of 383 amino acids. Hydropathy analysis of this protein indicates that it probably forms 12 transmembraneous helices. In a mutant, possessing only the NaH-antiporter, the napA gene was disrupted by homologous recombination. The resultant strain failed to grow in sodium-rich media, and vesicles isolated from these cells exhibited a defect in sodium proton antiport activity. We conclude that the napA gene codes for a NaH-antiporter. The NapA protein does not exhibit significant homology to any protein in the EMBL genetic data bank. PMID- 1312091 TI - Intermolecular triplex formation distorts the DNA duplex in the regulatory region of human papillomavirus type-11. AB - A conformational distortion in the DNA duplex at the regulatory region of human papillomavirus type-11 next to an intermolecular triplex, formed with a synthetic oligonucleotide, was investigated with several chemical probes. The sequence targeted for triplex formation borders on the binding sites for the regulatory proteins encoded by the viral E2 open reading frame. Dimethyl sulfate, diethyl pyrocarbonate, and OsO4 all react to a greater extent with nucleotides in the duplex that are immediately adjacent to the triplex as compared to other bases throughout the duplex. This hypermodification was observed on both the polypurine and polypyrimidine strands of the duplex DNA. Similar hyperreactivity of bases flanking a triplex also was seen when the contiguous target polypurine tract was effectively extended by mutating interrupting pyrimidines in the human papillomavirus type-11 sequence to purines. We propose that this hyperreactivity is due to a structural distortion caused by the junction between the triplex and the duplex tracts. PMID- 1312092 TI - Mevalonate kinase is localized in rat liver peroxisomes. AB - Recent data suggest that rat liver peroxisomes play a critical role in cholesterol synthesis. Specifically, peroxisomes contain a number of enzymes required for cholesterol synthesis as well as sterol carrier protein-2. Furthermore, peroxisomes are involved in the in vitro synthesis of cholesterol from mevalonate and contain significant levels of apolipoprotein E, a major constituent of several classes of plasma lipoproteins. In this study we have investigated the subcellular localization of mevalonate kinase (EC 2.7.1.36; ATP:mevalonate-5-phosphotransferase). Mevalonate kinase is believed to be a cytosolic enzyme and catalyzes the phosphorylation of mevalonate to form mevalonate 5-phosphate. Mevalonate kinase has been purified from rat liver cytosol and a cDNA clone coding for rat mevalonate kinase has also been isolated and characterized. In this study, utilizing monoclonal antibodies made against the purified rat mevalonate kinase, we demonstrate the presence of mevalonate kinase in rat liver peroxisomes and in the cytosol. Each of these compartments contained a different form of the protein. The pI and the Mr of the peroxisomal protein is 6.2 and 42,000, respectively. The pI and Mr of the cytosolic protein is 6.9 and 40,000, respectively. The peroxisomal protein was also significantly induced by a number of different hypolipidemic drugs. In addition, we present evidence for the unexpected finding that the purified mevalonate kinase (isolated from the cytosol and assumed to be a cytosolic protein) is actually a peroxisomal protein. PMID- 1312093 TI - Alternative multimeric structures affect myogenin DNA binding activity. AB - The native molecular weight of the basic helix-loop-helix (bHLH) proteins myogenin, MyoD, and E12 was calculated from their mobilities on sucrose gradients and molecular sieve chromatography. The muscle bHLH proteins associate to form a variety of higher order complexes, most of which are larger than dimers. Homodimers bind to DNA sequences such as the MEF-1 site in the creatine kinase enhancer whereas homotetramers and larger forms do not recognize this DNA sequence. The ubiquitous bHLH protein E12 forms monomers or homodimers with little evidence for higher order complexes. Mixtures of myogenin and E12 show some heterodimeric structures, but most of the myogenin remains in large complexes. This result using purified proteins is also obtained in nuclear extracts from differentiated myotubes, in which most of the myogenin is present in large complexes that do not bind to the creatine kinase enhancer. A fusion protein containing only the myogenin HLH region forms large homomeric complexes. A model is presented in which each helix associates with a different subunit to form chains or ring structures to explain these observations. The partition of myogenin in nuclear extracts into dimers that recognize known DNA sequences and higher order complexes that do not raises important new issues concerning the regulation of skeletal muscle bHLH protein activity during myogenesis. PMID- 1312094 TI - Immunolocalization of membrane-associated CTP:phosphocholine cytidylyltransferase in phosphatidylcholine-deficient Chinese hamster ovary cells. AB - The location of CTP:phosphocholine cytidylyltransferase in Chinese hamster ovary (CHO) cells made deficient in phosphatidylcholine was determined by immunofluorescence techniques. A rabbit polyclonal antibody was raised against a synthetic peptide corresponding to the amino-terminal 17 amino acid residues of rat liver cytidylyltransferase. The antibody recognized both native and denatured cytidylyltransferase from both rat liver and CHO cells. CHO cells were treated with phospholipase C to alter the lipid composition of the plasma membrane and to elicit translocation of cytidylyltransferase from the less active soluble pool to an activated membrane fraction. Visualization of cytidylyltransferase by indirect immunofluorescence revealed staining of the nuclear envelope in phospholipase C treated cells but not in untreated cells. CHO cells were also starved for choline and supplemented with a choline analogue to provide an alternative technique of rendering the cells phosphatidylcholine-deficient. Although this treatment should affect different cellular membranes than those affected by phospholipase C treatment, cytidylyltransferase still translocated to the nuclear envelope, as shown by indirect immunofluorescence. These results indicate that activated, membrane-bound cytidylyltransferase is associated with the nuclear membrane and suggest that the nuclear membrane may be a site of de novo phosphatidylcholine synthesis. PMID- 1312095 TI - Culture of human osteoblasts on demineralised human bone. Possible means of graft enhancement. AB - We cultured human osteoblasts from trabecular bone explants and confirmed their phenotype by alkaline phosphatase assay, increased cyclic adenosine monophosphate production in response to prostaglandin E2 and radiographic micro-analysis of nodules of calcification. The osteoblasts were seeded on to demineralised human bone fragments and examined at ten-day intervals over a 50-day period by scanning electron microscopy. During this time the bank bone became progressively repopulated by the cultured osteoblasts. This system may offer a means of graft enhancement in elective orthopaedic and maxillofacial surgery by delivery of cultured autologous human osteoblasts to bone defects. PMID- 1312096 TI - MRI of small hepatocellular carcinoma: comparison with US, CT, DSA, and Lipiodol CT. AB - Thirteen cirrhotic patients with 27 nodules of hepatocellular carcinoma less than 3 cm (small HCC) were examined with ultrasonography (US), MR, pre- and postcontrast CT, digital subtraction angiography (DSA), and CT after injection of Lipiodol (Lipiodol-CT). The accuracy of MR was compared with other diagnostic modalities and MR morphologic and the signal intensity features of HCC were investigated. The detection rate by MR was 63%, by US 67%, by CT 50%, by DSA 74%, and by Lipiodol-CT 93%. The Mc Nemar test showed no difference between the detection rates of MR and CT, MR and DSA, MR and US, and Lipiodol-CT and DSA; however, the differences between the detection rates of MR and Lipiodol-CT and CT and Lipiodol-CT were statistically significant (p less than or equal to 0.05). The difference in sensitivity between the detection rates of Lipiodol-CT and US was just above the level considered significant (P less than or equal to 0.065). On T1- and T2-weighted spin echo images 83% of small HCC were hyperintense relative to the surrounding liver parenchyma. Pseudocapsule was observed in 58% of lesions on T1-weighted images in particular. We believe that US is still the best diagnostic technique for the screening of HCC. We prefer MR to CT as a second level examination to support US in noninvasive diagnosis of small HCC, since MR gives the same or slightly better results than CT without the need of ionizing radiation and large amounts of iodized contrast medium. In our opinion, more invasive examinations, such as DSA and Lipiodol-CT, cannot be avoided in cases where an exact knowledge of the number of lesions is essential for the choice of therapy. PMID- 1312098 TI - Delayed enhancement of fibrotic areas in hepatic masses: CT-pathologic correlation. AB - We report a histological analysis of the areas of high density in the postequilibrium and delayed phase CT in 43 focal hepatic lesions. The cases consisted of 16 cholangiocellular carcinomas, 9 hepatocellular carcinomas (including a sclerosing type of hepatocellular carcinoma and a combined hepatocellular-cholangiocellular carcinoma), 13 metastases, 2 granulomas, an inflammatory pseudotumor, a malignant lymphoma, and an epithelioid hemangioendothelioma. Computed tomography was performed after hepatic angiography using 40-50 g iodine and arteriographic CT using 35 g iodine. The areas of delayed enhancement corresponded histologically to fibrotic tissues, from inflammatory change to extensive fibrosis. PMID- 1312097 TI - Differentiation between hepatoma and hemangioma with inversion-recovery snapshot FLASH MRI and Gd-DTPA. AB - Thirty-eight patients with focal liver tumors (20 hepatomas, 18 hemangiomas) were studied by dynamic sequential inversion recovery (IR) snapshot fast low angle shot (FLASH) MR imaging with Gd-DTPA. Immediately after 0.05 mmol/kg Gd-DTPA was administered intravenously for 2-3 s followed by flushing with normal saline for 4-5 s, 10 images were obtained in the first 20 s (time zero is the end of flush, early phase). Then, one image every 30 s from 1 to 3 min (late phase) and images at 5 min and 7 min (delayed phase) were obtained serially. Hepatomas showed total enhancement in 18 of 20 patients in the early phase, and isointense or low intensity enhancement with respect to the surrounding liver parenchyma in 18 patients in the late to delayed phases. Hemangiomas showed peripheral enhancement in 14 patients in the early phase, but did not show total enhancement (except for two hemangiomas less than 3 cm in size) in the early phase, and showed high intensity enhancement in 15 patients in the late phase. Ninety percent of hepatomas and 82% of hemangiomas showed their characteristic enhancement patterns in the early to delayed phases. We conclude that dynamic sequential IR snapshot FLASH MR images enhanced with Gd-DTPA can facilitate differentiation between hepatomas and hemangiomas. PMID- 1312099 TI - Effects of regional systolic asynchrony on left ventricular global diastolic function in patients with coronary artery disease. AB - Patients with coronary artery disease often have impaired left ventricular diastolic filling despite normal global systolic function. The influence of regional systolic asynchrony on diastolic function was assessed by radionuclide angiography in 60 patients with coronary artery disease and normal ejection fraction at rest: group 1 (n = 30) with normal wall motion at rest and group 2 (n = 30) with abnormal wall motion. Data were compared with those obtained from 19 normal volunteers. Age, heart rate, ejection fraction and echocardiographic end diastolic dimension did not differ among the three groups. Peak filling rate in group 1 and group 2 was similar (2.5 +/- 0.5 and 2.3 +/- 0.6 end-diastolic counts/s, respectively) and significantly lower than that in the normal subjects (2.8 +/- 0.7 end-diastolic counts/s; p less than 0.01 vs. group 2, p less than 0.05 vs group 1). Time to peak filling rate was prolonged in group 2 (184 +/- 27 ms) compared with that in normal subjects (162 +/- 19 ms; p less than 0.01) and group 1 (172 +/- 15 ms; p less than 0.05). Left ventricular end-diastolic pressure was significantly higher in group 2 than in group 1 (14 +/- 7 vs. 10 +/- 5 mm Hg, respectively; p less than 0.05). Asynchrony was assessed by sector analysis of the radionuclide left ventricular region of interest. Diastolic asynchrony was similar in the two patient groups (30 +/- 23 ms in group 2, 26 +/- 16 ms in group 1) and was higher in both groups than in the normal subjects (16 +/- 8 ms; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312100 TI - An experimental model of acute and subacute viral myocarditis in the pig. AB - Twenty-six young pigs were infected with encephalomyocarditis virus, observed clinically, studied at intervals by noninvasive and invasive methods to assess cardiac function and eventually examined pathologically. All infected animals appeared ill, usually manifesting diminished appetite, lethargy and fever. Spontaneous mortality occurred either 1 to 4 or 20 to 21 days after infection. Electrocardiographic abnormalities, seen in the majority of animals, comprised ST T wave changes, conduction disturbances or ventricular ectopic rhythm. The majority of animals manifested echocardiographic evidence of left ventricular dilation and decreased systolic function, which improved with time in some animals. Hemodynamic studies revealed elevation of biventricular filling pressures in 3 of 10 animals; as a group, infected animals manifested significantly elevated right ventricular filling pressures. In selected animals, the feasibility of gallium scans as well as left ventriculography and coronary angiography was demonstrated. At autopsy, heart weight/body weight ratio was significantly elevated in infected animals. The heart of all but two animals showed active myocarditis associated with fibrosis and focal calcification in the later stages. In general, the cardiovascular manifestations were parallel with those seen in acute and subacute myocarditis in humans. It is concluded that encephalomyocarditis infection in the pig is a large animal model of viral myocarditis suitable for assessing alterations in the structure and function of the cardiovascular system and the effects of interventions. PMID- 1312101 TI - The effects of eosinophil-granule major basic protein on lung-macrophage superoxide anion generation. AB - The effects of major basic protein (MBP) on superoxide anion release in vitro from normal guinea pig (GP) alveolar macrophages (AM) was determined. Native MBP at 55 micrograms/ml had an immediate effect (reduction) on phorbol myristate acetate (PMA)-induced (p less than 0.01) and spontaneous (p = 0.055) superoxide (O2-) release by GP AMs. A similar effect was not observed from AMs incubated for 24 hours with MBP before assessment of O2- release. However, after AMs were incubated with MBP for 48 hours, again there was a significant reduction observed in both PMA-induced (p = 0.01) and spontaneous (p = 0.002) O2- release compared to that of control cultures. The immediate effect of MBP on AM O2- release was not due to cytotoxicity of MBP for AM. In contrast, the effect observed after 48 hours of culture was due, in part, to a direct toxic effect of the MBP on the AM because the viability of AM cultured for 48 hours with MBP (55 micrograms/ml) was 63.6% +/- 13% compared to the viability of control cultures of AM that was 83.9% +/- 7%; p = 0.03. The effect of MBP on AM O2- release at 48 hours was progressive over concentrations ranging from 2 to 55 micrograms/ml. These data suggest that native MBP can affect adversely PMA-induced and spontaneous release of O2- by GP AMs and that this effect depends only in part on the cytotoxic properties of MBP. PMID- 1312102 TI - Cyclic AMP-independent effects of cholera toxin on B cell activation. II. Binding of ganglioside GM1 induces B cell activation. AB - Although the physiologic function of gangliosides is unknown, evidence suggests they play a role in the regulation of cell growth. The binding of ganglioside GM1 by recombinant B subunit of cholera toxin (rCT-B) inhibited mitogen-stimulated B cell proliferation without elevating intracellular cAMP. CT-B paradoxically enhanced the expression of MHC class II (Ia) molecules and minor lymphocyte stimulating determinants without altering the expression of some other immunologically relevant B cell surface Ag. Increased expression of Ia was not detected until 4 h after stimulation, kinetics similar to those seen when B cells are stimulated with anti-Ig antibody or IL-4, suggesting that the enhancement was not the result of redistribution of existing cell surface markers but rather the result of a new metabolic event. Both the inhibitory and stimulatory effects of CT-B could be blocked by incubation of CT-B with ganglioside GM1. Furthermore, enhancement of the CT-B-mediated effect was seen when additional ganglioside GM1 was incorporated into the B cell membrane. rCT-B with a mutation that interfered with its binding to ganglioside GM1 did not enhance Ia expression. Taken together, these results indicate that the observed effects of CT-B were most likely mediated through the binding of cell surface ganglioside GM1. CT-B mediated stimulation of Ia expression provides a potential explanation for the previously described ability of CT-B to act as an immunoadjuvant. These results suggest that the binding of ganglioside GM1 has multiple B cell growth-regulating effects. PMID- 1312103 TI - Bacterial lipopolysaccharide up-regulates platelet-activating factor-stimulated Ca2+ mobilization and eicosanoid release in human Mono Mac 6 cells. AB - When human monocytic Mono Mac 6 cells were treated with bacterial LPS (10 ng/ml, 72 h), they showed an increase in phagocytic activity, superoxide anion production, and expression of monocyte/macrophage-associated cell surface Ag. In these more mature (LPS-treated) cells but not in untreated cells, platelet activating factor (PAF) (100 nM) produced a three- to fourfold increase in cytosolic free Ca2+ concentration. The cytosolic free Ca2+ concentration increase was inhibited by the PAF receptor antagonist L-659,989 (10 microM) and by EGTA (2 mM), indicating receptor-dependent Ca2+ influx. Furthermore, L-659,989 (10 microM), as well as PAF (1 microM), inhibited specific [3H]PAF binding in LPS treated but not in untreated cells. Consistent with these results, PAF (100 nM) stimulated release of arachidonic acid and thromboxane B2 only in LPS-treated cells, and this could be inhibited by L-659,989 (10 microM) and EGTA (2 mM). Our data indicate that LPS up-regulates PAF-induced Ca2+ influx, resulting in arachidonic acid and eicosanoid release in Mono Mac 6 cells. PMID- 1312104 TI - Phospholipase C-gamma 1 is translocated to the membrane of rat basophilic leukemia cells in response to aggregation of IgE receptors. AB - Aggregation of the high affinity receptor for IgE (Fc epsilon RI) on the surface of mast cells results in the rapid hydrolysis of membrane inositol phospholipids by phospholipase C (PLC). Although at least seven isoenzymes of PLC have been characterized in different mammalian cells, the isoenzyme involved in Fc epsilon RI-mediated signal transduction and the mechanism of its activation have not been demonstrated. We now report that PLC-gamma 1 is translocated to the membrane of mast cells after aggregation of Fc epsilon RI. Activation of rat basophilic leukemia cells, a rat mast cell line, with oligomeric IgE resulted in an increase in PLC activity in washed membrane preparations in a cell free assay containing exogenous [3H]phosphatidylinositol (PI). The increase in PLC activity has the same dose-response to oligomeric IgE as receptor mediated hydrolysis of inositol lipids (PI hydrolysis) in intact cells. Analysis by Western blot probed with anti PLC-gamma 1 antibody revealed that there is a three- to fourfold increase in PLC gamma 1 in membranes from activated cells. The increase in PLC activity is augmented a further 20% by the addition of orthovanadate to the incubation medium suggesting that a tyrosine phosphatase is involved in the down-regulation of this phenomenon. These findings demonstrate translocation of PLC-gamma 1 to the membrane following activation of a receptor which does not contain intrinsic tyrosine kinase activity. Activation of PLC-gamma 1 by this pathway may account for Fc epsilon RI-mediated PI hydrolysis. PMID- 1312105 TI - Coxsackievirus B3-induced production of tumor necrosis factor-alpha, IL-1 beta, and IL-6 in human monocytes. AB - Infections by coxsackievirus B3 (CVB3) have previously been shown to cause acute and chronic myocarditis characterized by a heavy mononuclear leukocyte infiltration and myocyte necrosis. Because clinical and experimental evidence suggested that cardiac damage may result from immunologic rather than viral mechanisms, we examined in this study the in vitro interaction of CVB3 with human monocytes. CVB3 was capable of infecting freshly harvested monocytes as revealed by immunofluorescence and release of infectious virus particles. Virus infection did not reduce monocyte viability but, on the contrary, enhanced spreading and adherence. In a dose-dependent manner, CVB3 stimulated the release of cytokines from monocytes. Whereas a potent production of TNF-alpha, IL-1 beta, and IL-6 was dependent on exposure to infectious CVB3, IFN release was also induced by UV inactivated virus. On a molecular level, CVB3 stimulated cytokine gene expression as shown by a marked TNF-alpha, IL-1 beta, and IL-6 mRNA accumulation. Supernatants of CVB3-infected monocytes displayed cytotoxic activity against Girardi heart cells which could be abrogated by an anti-TNF-alpha antiserum. These data suggest that CVB3-induced cytokine release from monocytes may participate in virus-induced organ damage such as myocarditis, which may either occur by a direct cytotoxicity of cytokines or by activation of cytotoxic lymphocytes. PMID- 1312106 TI - Galactose receptors and presentation of HIV envelope glycoprotein to specific human T cells. AB - Recognition of viral Ag and of the envelope glycoprotein of HIV (gp120) in particular by human Th cells is critical in the immune response to the viral Ag which includes antibody production and generation of cytotoxic cells. Procedures to increase antigenicity of gp120 are highly desirable in a vaccine perspective. Therefore, to induce activation of gp120-specific T cells by a liminal dose of Ag we enhanced uptake of gp120 by exploiting the galactose receptors on APC. Terminal sialic acid residues were removed by neuraminidase treatment from the carbohydrate side chains of the heavily glycosylated gp120. Galactose residues were exposed and hence recognized by galactose receptors on APC. The experiments demonstrated that 1) human monocytes and dendritic cells, but not cells of the B lineage, bear galactose receptor; 2) galactose receptors are indeed involved because enhanced presentation is inhibited by galactose and acetylgalactosamine and competed for by other asialoglycoproteins; 3) galactose receptors mediate internalization of Ag in intracellular compartments that intersect the processing and presenting pathways, resulting in activation of specific T cells; 4) antigenicity of gp120 for specific T cells can be enhanced by the exposure of galactose residues. PMID- 1312107 TI - Epidermal cell-polymorphonuclear leukocyte cooperation in the formation of leukotriene B4 by transcellular biosynthesis. AB - The cellular origin of Leukotriene B4, a potent pro-inflammatory agent that is present in psoriatic lesions, has not been completely ascertained. The present study was performed in order to assess the possible contribution of epidermal cells to leukotriene B4 synthesis through 5-lipoxygenase or by means of transcellular metabolism of the epoxide intermediate leukotriene A4 from activated polymorphonuclear leukocytes. The metabolism of exogenous arachidonic acid in fresh human epidermal cell, polymorphonuclear leukocyte or mixed suspensions was determined by means of high-performance liquid chromatography. Epidermal cells transformed arachidonic acid mainly into 12-hydroxy eicosatetraenoic acid and prostaglandin E2. Formation of prostaglandins F2 alpha and D2, 12-hydroxy-eptadecatrienoic acid, and 15- and 11-hydroxy-eicosatetraenoic acids was also detected. We did not detect any eicosanoid derived from 5 lipoxygenase pathway. Mixed suspensions of polymorphonuclear leukocytes and epidermal cells (ratio 1:4) produced 1.72 times more leukotriene B4 than leukocytes alone under the same experimental conditions. Epidermal cells incubated with 5 microM authentic leukotriene A4 for 3 min yielded 2.954 +/- 0.27 pmoles/10(6) cells of leukotriene B4, which was characterized by co-elution with authentic standard and its ultraviolet absorption spectrum. These data demonstrate the existence of a leukotriene A4 epoxide hydrolase activity in human epidermal cells. Our results suggest that epidermal cells could cooperate in leukotriene B4 biosynthesis by transcellular metabolism of leukotriene A4 in lesions of psoriasis, and possibly other inflammatory dermatoses characterized by increased leukotriene B4 levels and prominent polymorphonuclear leukocyte infiltrates. PMID- 1312109 TI - All-trans-retinoic acid treatment and retinoic acid receptor alpha gene rearrangement in acute promyelocytic leukemia: a model for differentiation therapy. AB - All-trans-retinoic acid (ATRA), a vitamin A derivative, is a safe and effective drug in the obtention of complete remission in acute promyelocytic leukemia (APL). ATRA is able to activate the maturation of malignant cells from patients with APL either in vitro or in vivo. Complete remission was obtained without any feature of aplastic phase and the severe bleeding diathesis rapidly disappeared. The major adverse effect is the occurrence of hyperleukocytosis which is prevented by the addition of chemotherapy. A progressive acquired resistance appears during ATRA treatment and prolonged event free survival time is obtained after consolidation with cytotoxic drugs. In APL the retinoic acid receptor alpha gene is rearranged and fused with a novel gene called PML. The hybrid PML-RAR product could have a role in the leukemogenesis blocking the effect of the normal RAR on target genes. Retinoic acid exerts a differentiating effect either by the induction of a normal activity of the aberrant product in the presence of pharmacological concentration, or by an over-expression of the normal allele. The results obtained by cellular and molecular biology gave opportunities to confirm the diagnosis, to follow the assessment of the minimal residual disease and to understand the acquired resistance. PMID- 1312108 TI - Seroreactivity against HPV 16 E4 and E7 proteins in renal transplant recipients and pregnant women. PMID- 1312110 TI - [Antiproliferative actions of medroxyprogesterone acetate (MPA) to human ovarian cancer cell lines in vitro]. AB - The cytostatic effect of medroxyprogesterone acetate (MPA; an oral luteohormone preparation) on two cell lines of ovarian carcinoma cultured in vitro (SHIN-3 and MN-1) was studied. At the same time, changes in the morphology and colony formation of these cancer cells after exposure to the drug were examined. 1) The doubling time of SHIN-3 cells in the logarithmic growth phase was prolonged 2.5 times at a MPA dose of 10(-8)M and 3.2 times at a MPA dose of 10(-5)M. The drug, however, exerted no significant cytostatic effect on MN-1 cells. 2) When the IC50 of MPA was assessed by counting live SHIN-3 cells in an FCS-added medium, it was 2.7 x 10(-5)M. When the same assessment was done with a medium without serum, IC50 was 6.4 x 10(-6)M. 3) After 120 hours of incubation in a medium containing 10(-8)M of MPA, CA125 (a tumor marker) production by SHIN-3 cells was suppressed by 35%. The suppression rate was 79% for SHIN-3 cells incubated in a medium containing 10(-5) of MPA. 4) The cytoplasm of SHIN-3 cells, incubated in a MPA added medium, showed the formation of small mucous vacuoles and expansive degeneration, accompanied by a marked increase in size and thinning of the nucleus. 5) In an experiment on colony formation with collagen gel, the colony size decreased MPA concentration dependently, and was accompanied by the appearance of lobulated colonies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312111 TI - [Usefulness of magnetic resonance imaging (MRI) in the detection of the lesions of gestational trophoblastic disease--comparison with computed tomography and digital subtraction angiography]. AB - Twenty patients with gestational trophoblastic disease (GTN) were examined by Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Digital Subtraction Angiography (DSA), to evaluate their usefulness in the diagnosis of the disease. The lesions of hydatidiform mole were mainly composed of molar vesicles, dilated vessels and hemorrhage which were depicted as small round high intensity lesions on the T2-weighted images and as tree-like low intensity lesions and high or low intensity lesions of various shapes in the T1-, T2 weighted images. These MRI findings closely corresponded to the histopathological findings. On the other hand, CT findings obtained with hydatidiform mole were characterized by filling defects or a small round low density area on contrast enhanced images. The detection ratio for intramural lesions of invasive mole and choriocarcinoma by MRI was 83% (5/6), while that by CT was 50% (3/6). The obliteration of the junctional zone and interruption of the myometrium observed in MRI were significant signs suggesting intramural invasion of the disease. In fact, these signs in MRI were observed in all of the six cases with invasive mole or choriocarcinoma examined. In conclusion, MRI is a powerful means for the determining the intramural invasive mole and choriocarcinoma. Thus more accurate diagnosis of GTN will be obtained with the combined use of MRI and DSA. PMID- 1312112 TI - [The significance of measurement of serum type IV 7S collagen on administration of DHA-S]. PMID- 1312113 TI - Hazard of testing smokeless gunpowder with nitric acid. PMID- 1312114 TI - An acidic region of the 89K murine cytomegalovirus immediate early protein interacts with DNA. AB - The product of the ie1 gene, the regulatory immediate early protein pp89 of murine cytomegalovirus (MCMV), interacts with core histones, which can mediate the association of pp89 with DNA. We report the capacity of pp89 to interact directly with DNA in the absence of cellular proteins. After separation of proteins by SDS-PAGE, pp89 bound ds- and ssDNA, with a preference for ssDNA. Binding to specific DNA sequences in the MCMV genome was not detected. The DNA binding region of pp89 was located to amino acids 438 to 534 by analysis of deletion mutants expressed as beta-galactosidase or TrpE fusion proteins. This region is identical to the highly acidic C-terminal region spanning amino acids 424 to 532. The human cytomegalovirus IE1 protein, which contains a similar extended C-terminal acidic region, does not react with DNA under the same experimental conditions. PMID- 1312115 TI - Characterization of the varicella-zoster virus gene 61 protein. AB - The protein predicted to be encoded by varicella-zoster virus (VZV) gene 61 exhibits limited amino acid sequence similarity to the herpes simplex virus type 1 nuclear phosphoprotein Vmw110, which functions as a transcriptional activator. The gene 61 protein was expressed in its entirety, or as an amino- or carboxy terminal fragment in Escherichia coli and vaccinia virus recombinants, and monospecific rabbit antisera were raised against an E. coli fusion between beta galactosidase and the majority of the gene 61 protein. Use of the antisera showed that the gene 61 protein is present in VZV-infected cell nuclei as a heterogeneous phospho-protein of Mr62K to 65K. Phosphorylation occurs in the amino- and, to a lesser extent, carboxy-terminal portions of the protein. The carboxy-terminal region directs transport of the protein to the nucleus, whereas the amino-terminal region, which contains a potential zinc-binding domain, is responsible for a punctate distribution. Preliminary mapping data indicated that gene 61 is transcribed as a 1.8 kb mRNA which initiates about 65 bp upstream from the translation initiation codon, at a position located appropriately with respect to potential regulatory elements. PMID- 1312116 TI - On the cellular localization of the components of the herpes simplex virus type 1 helicase-primase complex and the viral origin-binding protein. AB - We constructed recombinant viruses based on the herpes simplex virus type 1 mutant tsK which individually were able to express the products of four viral DNA replication genes (UL5, UL8, UL9 and UL52) in the absence of any of the other proteins required for viral DNA synthesis. These viruses were used in immunofluorescence experiments to investigate the cellular localization of the four replication proteins expressed. The results demonstrated that all three components of the viral helicase-primase complex (UL5, UL8 and UL52 proteins) must be co-expressed to allow their efficient localization to the nucleus. Since the UL5 and UL52 proteins together form a complex which is enzymatically indistinguishable from a complex formed from all three proteins, a possible role of the UL8 protein may be in facilitating nuclear uptake. The UL9 protein (origin binding protein) efficiently entered the cell nucleus when expressed alone. Both UL9 protein and the tripartite helicase-primase complex exhibited patterns of fluorescence which resembled the 'pre-replicative sites' described previously. PMID- 1312117 TI - The myristylated virion proteins of herpes simplex virus type 1: investigation of their role in the virus life cycle. AB - Herpes simplex virus type 1 (HSV-1) gene UL11 encodes a myristylated virion protein. In this paper we have characterized the UL11 product further and investigated its role in the virus life cycle. Wild-type HSV-1 strain 17syn+ expresses three electrophoretically distinguishable UL11 polypeptide species. Analysis of single plaque isolates demonstrated that two virus populations exist within the 17syn+ stock: a major population encoding only the two higher Mr species, and a minor population encoding the lowest Mr species alone. DNA sequence analysis suggests that the latter polypeptide differs from the former ones at a single amino acid residue only. The UL11 polypeptides are synthesized as delayed early gene products and are phosphorylated in vitro. Following subcellular fractionation of infected cells, they are found predominantly associated with membranes. Within the virus particle, they appear to reside within the tegument. An insertion mutant containing the lacZ gene from Escherichia coli within the UL11 open reading frame is viable in tissue culture, although it gives smaller plaques and is impaired for growth compared to the wild type parent or revertant viruses; it does not have a temperature-sensitive or host-range phenotype. Thus, although required for efficient replication, the myristylated HSV-1 virion protein, in contrast to those of many other viruses, is not essential for virus growth in tissue culture. PMID- 1312118 TI - Distribution and substrate specificity of intracellular proteolytic processing enzyme(s) for paramyxovirus fusion glycoproteins. AB - Intracellular proteolytic processing of fusion glycoprotein precursors (F0) of paramyxoviruses, i.e. a virulent strain of Newcastle disease virus (NDV), parainfluenza virus type 3 (PIV3) and simian virus 5 (SV5), was examined in NALM6 and BSC40 cells and compared with that in LLCMK2 cells to investigate the distribution of the virus-activating protease(s) among the cells and its substrate specificity. BSC40 cells lack a processing endoprotease of the neuropeptide precursor, pro-opiomelanocortin (POMC), which possesses multiple cleavage sites at pairs of basic residues, Lys-Arg and Arg-Arg, a motif similar to that found in the cleavage site of the F0 proteins. In NALM6 cells, only small amounts of the F0 protein of virulent NDV was cleaved whereas those of PIV3 and SV5 were efficiently cleaved. In BSC40 cells the F0 proteins of these three viruses were cleaved normally as well as in LLCMK2 cells. The processing inhibitors monensin, chloroquine and A23187 suppressed the F0 cleavage in the three cell types. These results indicate that both NALM6 and BSC40 cells possess virus-activating proteases similar to that of LLCMK2 cells, but suggest that the enzyme of NALM6 may be slightly different in its substrate specificity from those of BSC40 and LLCMK2. The results also suggest that the virus-activating proteases are different in their distribution and substrate specificity from the processing enzyme of POMC. PMID- 1312119 TI - Internalization of intact poliovirus by HeLa cells as shown by subcellular fractionation in isoosmotic Nycodenz gradients. AB - HeLa cells were infected with radiolabelled poliovirus at different temperatures, and the intracellular distribution of input radioactivity was studied. To this end, homogenates were fractionated by rate zonal centrifugation in linear isoosmotic (2 to 30%) Nycodenz gradients. Further purification of subcellular fractions was achieved by recentrifugation to equilibrium in 10 to 30% Nycodenz. Temperatures were kept below 30 degrees C to prevent virus capsid modification. Under these conditions, the cell-associated virions remained fully infectious. Below 18 degrees C, most of the viral label was recovered from a bottom region (BR) of the rate zonal gradients. Marker enzyme analysis and antibody accessibility showed that the BR consisted of virions bound to the plasma membrane. Between 18 degrees C and 26 degrees C, viral label also accumulated in a top region (TR) of the rate zonal gradients. According to the criterion of antibody accessibility, the virions associated with the TR were present within intracellular structures, probably lipid membranes. Electron microscopy confirmed the presence of vesicles and tubules in this region of the gradient. No correlation was found between the TR and endosomal, lysosomal or plasma membrane markers. The TR equilibrated at low density (1.10 g/ml) in Nycodenz (free virus, 1.31 g/ml). The results confirm that intact poliovirions can enter the cell and do so via lipid-bound vesicles. PMID- 1312120 TI - Identification and characterization of foot-and-mouth disease virus O1 Burgwedel/1987 as an intertypic recombinant. AB - The foot-and-mouth disease virus field isolate Burgwedel/1987 subtype O1 was found to differ genetically from the antigenically related strain O1 Kaufbeuren within the region encoding the non-structural proteins. This genetic difference was indicated by the RNase mismatch cleavage method and confirmed by nucleotide sequencing. An alignment of sequences encoding proteinase 3C of the Burgwedel isolate and several other virus strains identified this isolate as an intertypic recombinant; the parent strains were O1 Kaufbeuren and a subtype C1 strain. Recombination occurred between nucleotide positions 5493 and 5521, within the region encoding peptide 3B1. Thus, the 5' three-quarters of the O1 genome were fused to the 3'-terminal quarter of the C1 genome. Other contemporary isolates from the same district are not recombinants. Sequence alignment distinguished four patterns of proteinase 3C-coding sequences among the virus strains analysed: subtypes A12, C1 and O1 exhibit one pattern each, and another pattern is common to subtypes A5, A10 and O2. PMID- 1312121 TI - The nucleotide sequences of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant. AB - We have shown previously that, compared to other enteroviruses, the coxsackievirus A9 (CAV-9) prototype strain, Griggs, contains a C-terminal extension to the capsid protein VP1 and that within this extension there is an RGD (arginine-glycine-aspartic acid) motif. To determine whether these features are found in other CAV-9 strains and therefore analyse whether they are likely to be functionally important, we have determined the nucleotide sequence of the appropriate region from five strains, isolated over a 25 year period. The results indicate that there is considerable diversity between the strains and there is little correlation between nucleotide sequence identity and date of isolation. All isolates exhibit the VP1 extension and although its amino acid sequence is otherwise variable, the RGD motif is common to all. This conservation of sequence, within a region which can otherwise vary, implies that the RGD sequence must be functionally significant. The VP1 extension shows similarity to sequences found in foot-and-mouth-disease virus strains and to part of the precursor of the cellular protein, human transforming growth factor beta, and the possible significance of these observations is discussed. PMID- 1312122 TI - Shedding of a rhinovirus minor group binding protein: evidence for a Ca(2+) dependent process. AB - Soluble rhinovirus minor group binding activity was found to be shed into the medium upon incubation of HeLa cells at 37 degrees C. Although substantial amounts of this protein were released, no decrease of virus binding to the cell surface was seen. When the membrane-associated receptor was stripped from the cells with trypsin, virus binding was rapidly restored from an intracellular pool even in the absence of de novo protein synthesis. The release of this 85K virus binding activity was inhibited by metal chelators such as EDTA, EGTA or 1,10 phenanthroline. The potential involvement of a Ca(2+)-dependent protease and/or a phospholipase in this process is discussed. PMID- 1312123 TI - Nucleotide sequences of normal and rearranged RNA segments 10 of human rotaviruses. AB - Normal and rearranged RNA segments 10 of group A rotaviruses isolated from a chronically infected immunodeficient child were amplified by the polymerase chain reaction as full-length cDNA copies, and were subsequently cloned and sequenced. Compared with the nucleotide sequence of the normal RNA segment 10, the rearranged form contains a partial non-coding duplication at its 3' end and several point mutations. The normal RNA segment 10 was similar to that of bovine rotavirus. PMID- 1312124 TI - Demonstration of a hepatitis C virus-specific antigen predicted from the putative core gene in the circulation of infected hosts. AB - An ELISA was used to detect a protein derived from the core gene of the hepatitis C virus (HCV) in human plasma. The solid phase antibody in the assay was a murine monoclonal antibody against a synthetic peptide deduced from the putative core gene of HCV (residues 39 to 74). An enzyme-labelled affinity-purified human antibody directed at another region within the HCV core (residues 5 to 23) was the second antibody tracer. The ELISA had a sensitivity capable of detecting a few ng/ml of the HCV core polypeptide expressed in Escherichia coli. Core antigen activity in plasma of infected hosts was detected after treatment of HCV RNA-rich fractions from buoyant density centrifugation with the detergent Tween 80. There was a direct correlation between core antigen ELISA values of a plasma fraction and intensities of polymerase chain reaction signals for HCV RNA. These observations are consistent with the proposal that the N-terminal sequence of the predicted polyprotein of HCV is a nucleocapsid protein, and that improved core antigen assays may correlate with viraemia. PMID- 1312125 TI - Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. AB - Based on variation in nucleotide sequence within restricted regions in the putative C (core) gene of hepatitis C virus (HCV), four groups of HCV have been postulated in a panel of 44 HCV isolates. They were provisionally designated types I, II, III and IV. A method for typing HCV was developed, depending on the amplification of a C gene sequence by polymerase chain reaction using a universal primer (sense) and a mixture of four type-specific primers (antisense). HCV types were determined by the size of the products specific to each of them. Type II was found in HCV samples from 131 (82%) of 159 blood donors, more often than in those from 48 (60%) of 80 patients with non-A, non-B (NANB) liver disease in Japan (P less than 0.01). In 11 haemophiliacs who had received imported coagulation factor concentrates, type I was found in five, as against type II in four. Double infection with two different HCV types was found in two patients with chronic NANB liver disease (types I and II; II and III) and two haemophiliacs (types I and II; I and III). HCV types were identical in mother and baby in each of two examples of perinatal transmission, and were also identical in donor and recipient in a case of accidental needle exposure. PMID- 1312126 TI - Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction. AB - The genomic RNA of hepatitis C virus (HCV) in the plasma of volunteer blood donors was detected by using the polymerase chain reaction in a fraction of density 1.08 g/ml from sucrose density gradient equilibrium centrifugation. When the fraction was treated with the detergent NP40 and recentrifuged in sucrose, the HCV RNA banded at 1.25 g/ml. Assuming that NP40 removed a lipid-rich surface coat from HCV, the 1.08 g/ml and 1.25 g/ml HCV RNA may correspond to intact HCV virions and nucleocapsids, respectively. The extraordinarily low density of the virion is unusual in comparison to the density of classified viruses. PMID- 1312127 TI - Baculovirus-expressed glycoprotein H of herpes simplex virus type 1 (HSV-1) induces neutralizing antibody and delayed type hypersensitivity responses, but does not protect immunized mice against lethal HSV-1 challenge. AB - We have shown previously that herpes simplex virus type 1 (HSV-1) glycoprotein H (gH) expressed by a baculovirus recombinant is transported to the cell surface in the absence of other HSV-1 gene products, and that the expressed gH has an apparent Mr similar to that of authentic HSV-1 gH. We report here that antibodies raised in mice to this baculovirus-expressed gH neutralize the infectivity of HSV 1 in vitro; this neutralizing activity was not complement-dependent. Mice vaccinated with gH also developed delayed type hypersensitivity (DTH) to HSV-1. This is the first report of expressed HSV-1 gH inducing neutralizing antibody or DTH responses in vaccinated animals. In contrast to the gH expressed in mammalian systems, the ability of this baculovirus-expressed gH to induce a neutralizing antibody response may be due to the inability of the mammalian expression system to transport gH to the cell surface. Despite inducing anti-HSV-1 neutralizing antibody and DTH responses, vaccination of mice with gH did not protect the mice against lethal intraperitoneal challenge with HSV-1. PMID- 1312128 TI - The herpes simplex virus type 1 tegument protein VP22 is encoded by gene UL49. AB - VP22 is a major tegument protein of herpes simplex virus type 1 and is highly phosphorylated in the infected cell. Indirect evidence exists to suggest that it is encoded by gene UL49, present in the BamHI F fragment of the genome. Using the polymerase chain reaction we have cloned the UL49 open reading frame into a mammalian expression vector under the control of the human cytomegalovirus immediate early gene promoter. After transfection into COS-7 cells expression of the gene product was detected by means of Western blotting and immunofluorescence. The results clearly indicate that the protein encoded by UL49 is VP22, and that in transfected cells it appears to have characteristics similar to those of the protein synthesized in infected cells. PMID- 1312129 TI - Comparison between in vitro neutralization titres and in vivo protection against homologous and heterologous challenge induced by vaccines prepared from two serologically distinct variants of foot-and-mouth disease virus, serotype A22. AB - Guinea-pigs were challenged with homologous or heterologous strains of foot-and mouth disease virus (FMDV) following vaccination with baby hamster kidney (BHK) monolayer cell-adapted or BHK suspension cell-adapted strains of FMDV serotype A22 Iraq 24/64. The protection afforded by these vaccines was analysed as a function of antigen dose and the in vitro serum virus neutralization titres achieved. The results show that the level of neutralizing antibody induced that afforded 50% protection was similar for both vaccines in homologous or heterologous challenge situations. However, although the dose of antigen required to achieve this titre against homologous virus was similar for the two vaccines, approximately 20-fold more of the suspension cell-adapted virus was required to elicit a protective titre against heterologous challenge compared to the dose of monolayer cell-adapted virus required. A synthetic peptide representing the amino acid sequence 135 to 167 of VP1, which is identical in the A22 Iraq 24/64 variant viruses, was shown to induce protection against both homologous and heterologous virus challenge. PMID- 1312130 TI - Sequence analysis of M2 mRNA of bovine respiratory syncytial virus obtained from an F-M2 dicistronic mRNA suggests structural homology with that of human respiratory syncytial virus. AB - The nucleotide sequences of the F and M2 mRNAs of strain A51908 of bovine respiratory syncytial virus (BRSV) were determined by sequencing cDNA of an intracellular dicistronic mRNA. Comparison of the F mRNA sequence with those of other BRSV strains showed that there was extensive sequence identity at both the nucleotide (95% identity) and amino acid (94% identity) levels. Alignment of the nucleotide and encoded amino acid sequences of M2 mRNA of BRSV with those of human respiratory syncytial virus (HRSV) M2 mRNA showed 69% identity at the nucleotide level and 80% identity at the amino acid level. The general features of BRSV F and M2 proteins are similar to those described previously for the HRSV proteins. The M2 mRNA of BRSV also contained a second internal, overlapping open reading frame (ORF) similar to one reported for HRSV. The predicted products of the second ORFs of BRSV and HRSV shared 43% amino acid identity. As described for HRSV, the 3'-terminal end of the M2 mRNA overlaps with the 5' end of the L gene by 68 nucleotides. The identity between the N-terminal regions of the L proteins of BRSV and HRSV is 75%. In addition, the intergenic sequence of the F-M2 gene junction of BRSV was determined. PMID- 1312131 TI - The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. AB - The expression patterns of 13 GABAA receptor subunit encoding genes (alpha 1 alpha 6, beta 1-beta 3, gamma 1-gamma 3, delta) were determined in adult rat brain by in situ hybridization. Each mRNA displayed a unique distribution, ranging from ubiquitous (alpha 1 mRNA) to narrowly confined (alpha 6 mRNA was present only in cerebellar granule cells). Some neuronal populations coexpressed large numbers of subunit mRNAs, whereas in others only a few GABAA receptor specific mRNAs were found. Neocortex, hippocampus, and caudate-putamen displayed complex expression patterns, and these areas probably contain a large diversity of GABAA receptors. In many areas, a consistent coexpression was observed for alpha 1 and beta 2 mRNAs, which often colocalized with gamma 2 mRNA. The alpha 1 beta 2 combination was abundant in olfactory bulb, globus pallidus, inferior colliculus, substantia nigra pars reticulata, globus pallidus, zona incerta, subthalamic nucleus, medial septum, and cerebellum. Colocalization was also apparent for the alpha 2 and beta 3 mRNAs, and these predominated in areas such as amygdala and hypothalamus. The alpha 3 mRNA occurred in layers V and VI of neocortex and in the reticular thalamic nucleus. In much of the forebrain, with the exception of hippocampal pyramidal cells, the alpha 4 and delta transcripts appeared to codistribute. In thalamic nuclei, the only abundant GABAA receptor mRNAs were those of alpha 1, alpha 4, beta 2, and delta. In the medial geniculate thalamic nucleus, alpha 1, alpha 4, beta 2, delta, and gamma 3 mRNAs were the principal GABAA receptor transcripts. The alpha 5 and beta 1 mRNAs generally colocalized and may encode predominantly hippocampal forms of the GABAA receptor. These anatomical observations support the hypothesis that alpha 1 beta 2 gamma 2 receptors are responsible for benzodiazepine I (BZ I) binding, whereas receptors containing alpha 2, alpha 3, and alpha 5 contribute to subtypes of the BZ II site. Based on significant mismatches between alpha 4/delta and gamma mRNAs, we suggest that in vivo, the alpha 4 subunit contributes to GABAA receptors that lack BZ modulation. PMID- 1312133 TI - Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells. AB - Because increasing evidence indicates that glial cells are a target of endothelin, we have characterized endothelin-induced phosphoinositide (PI) turnover and Ca2+ homeostasis in C6 glioma cells. Endothelin-1 (ET) increased formation of 3H-inositol phosphate (IP) from PI and elicited an increase in cytosolic free Ca2+ ([Ca2+]i) in rat C6 glioma. In the presence of Li+, the increase in 3H-inositol trisphosphate formation was rapid, reaching its peak at 5 min after stimulation. ET also elicited a rapid and sustained increase in [Ca2+]i in a dose-dependent manner (1-100 nM). The rank orders of efficacy for ET-related peptides in increasing [Ca2+]i were ET = ET-2 greater than sarafotoxin greater than ET-3. Both ET-mediated stimulation of IP formation and [Ca2+]i increase were largely inhibited in the absence of external Ca2+ but unaffected by the depletion of external Na+ and the presence of dihydropyridine derivatives or verapamil. Inorganic Ca2+ channel blockers Cd2+, La3+, and Mn2+ at 1 mM inhibited both responses induced by ET. Cross-desensitization and nonadditivity were observed for both events among ET-related peptides tested, but not between ET and ATP. Pretreatment of cells with pertussis toxin (PTX) attenuated the PI response to ET, but had no effect on ET-elicited [Ca2+]i increase. ET-induced Ca2+ mobilization (measured in Ca(2+)-free medium) was only transient and was inhibited by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate. Moreover, the intracellular Ca2+ pools mobilized by ET and ATP appeared to overlap, as indicated by their partial heterologous desensitization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312132 TI - The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. AB - In an effort to determine subunit compositions of in vivo GABAA receptors, the cellular localization of 13 subunit encoding mRNAs (alpha 1-alpha 6, beta 1-beta 3, gamma 2-gamma 3, delta) was determined in the rat olfactory bulb and cerebellum. Cerebellar granule cells expressed significant quantities of alpha 1, alpha 6, beta 2, beta 3, gamma 2, and delta mRNAs. They contained very much lower levels of alpha 4, beta 1, and gamma 3 mRNAs, and the alpha 2, alpha 3, alpha 5, and gamma 1 genes appeared to be silent. Purkinje cells contained only the alpha 1, beta 2, beta 3, and gamma 2 mRNAs. Putative Bergmann glial cells were found to contain the gamma 1 mRNA and possibly the alpha 2 mRNA. In the molecular layer, only the alpha 1, beta 2 and gamma 2 mRNAs were expressed in stellate/basket cells. The alpha 3 probe hybridized weakly to targets in the molecular layer. The inferior olivary nucleus contained significant quantities of alpha 2, alpha 4, and gamma 1 transcripts, with the alpha 1, alpha 3, beta 2, beta 3, and gamma 2 mRNAs also present. In the olfactory bulb, mitral cells were found to express the alpha 1, beta 1, beta 2, beta 3, and gamma 2 mRNAs strongly and the alpha 3 mRNA weakly. Tufted cells contained alpha 1, alpha 3, beta 2, beta 3, and gamma 2 mRNAs and, occasionally, the alpha 2 mRNA. In the internal granule cells the alpha 2, alpha 4, alpha 5, beta 3, and delta mRNAs were all present. Low levels of alpha 3, gamma 1, gamma 2, and gamma 3 mRNAs were also noted in these cells. Periglomerular cells expressed low levels of alpha 2, alpha 3, alpha 4, beta 2, beta 3, gamma 1, gamma 2, and gamma 3 mRNAs. No alpha 6 mRNA was present in the olfactory bulb. Correlations that are general ones from other brain regions are the colocalizations of alpha 1 beta 2, alpha 2 beta 3, and alpha 4 delta mRNAs. In both the olfactory bulb and cerebellum, alpha 1 beta 2 gamma 2 receptor cores are probably employed. The delta-subunit mRNA appears to codistribute with alpha subunit mRNAs (alpha 4 and alpha 6) associated with GABAA subunits that fail to bind benzodiazepine agonists. PMID- 1312134 TI - Cyclic AMP-dependent phosphorylation of the rat brain ryanodine receptor. AB - Phosphorylation of the rat brain ryanodine receptor was studied using a monoclonal antibody, Ry-1, against the cardiac ryanodine receptor. A large polypeptide with the same SDS-PAGE mobility as that of the canine cardiac receptor was detected in rat brain membranes by immunoblotting. The brain ryanodine receptor was solubilized from the microsomal membranes with 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and more than 85% of the solubilized receptor was immunoprecipitated by Ry-1. Immunoprecipitated receptors were phosphorylated by cAMP-dependent protein kinase. The ryanodine receptor was also expressed in cultured fetal rat brain neurons and was phosphorylated by treating the cells with dibutyryl cAMP. The number of cells showing a caffeine-induced Ca2+ transient was increased significantly in the phosphorylating condition. These results suggest that the Ca channel activity of the brain ryanodine receptor is regulated by cAMP-dependent phosphorylation. PMID- 1312135 TI - Acetylcholine synthesis and release is enhanced by dibutyryl cyclic AMP in a neuronal cell line derived from mouse septum. AB - Cholinergic properties of the SN56.B5.G4 cell line derived from the fusion of neurons of the mouse postnatal day 21 septum and the murine neuroblastoma cell line N18TG2 were investigated and correlated with morphological differentiation. In basal serum-containing growth medium, few cells developed neurites. Neurite extension occurred in cells grown for 2 d with forskolin or dibutyryl cAMP (dbcAMP) but not with butyrate. In cells treated with these compounds, the activity of ChAT and ACh content were two- to threefold higher relative to controls. The cells synthesized ACh from choline taken up by the sodium-dependent high-affinity transport. Forskolin-, dbcAMP-, and butyrate-treated cells (but not the controls) were capable of spontaneous and depolarization-evoked ACh release. The results indicate that the morphological and the neurochemical aspects of SN56.B5.G4 cell differentiation are independently regulated. PMID- 1312136 TI - Energy metabolism of rabbit retina as related to function: high cost of Na+ transport. AB - Experiments designed to examine the energy requirements of neurophysiological function were performed on isolated rabbit retina. Function was altered by photic stimulation or by function-specific drugs, and the response of energy metabolism was assessed by simultaneous measurements of O2 consumption and lactate production. In other experiments, the supply of O2 or glucose was reduced and the effect on energy metabolism and electrophysiological function was observed. Energy requirements under control conditions in darkness were high, with O2 consumption (per gm dry wt) at 11.3 mumol min-1, with lactate production at 14.8 mumol min-1, and with the derived value for glucose consumption at 9.3 mumol min 1 and for high-energy phosphate (approximately P) generation at 82.6 mumol min-1. Energy reserves were small. Removing glucose abolished the b-wave of the electroretinogram (ERG) with a t1/2 of 1 min, but did not immediately affect O2 consumption or the PIII of the ERG. Removing O2 caused increases of up to 2.7 fold in glycolysis (Pasteur effect) and caused both PIII and b-wave to fail, with a t1/2 of about 5 min. Neurotransmission through the inner retina was supported almost entirely by glycolysis, as evidenced by large increases in lactate production in response to flashing light and decreases in response to transmitter blockers (2.3-fold overall change), with no change in O2 consumption. Phototransduction, on the other hand, was normally supported by oxidative metabolism. The dark current accounted for 41% of the retina's O2 consumption. With O2 reduced, the dark current was partially supported by glycolysis, which accounts (at least in part) for the large Pasteur effect. Na+ transport by NaK ATPase accounted for about half of all energy used, as evidenced by the response to strophanthidin, that is, for 49% of the oxidative energy and 58% of the glycolytic energy. The t1/2 for the turnover of intracellular Na+ was calculated from these data to be less than 1 min. Changes in temperature caused changes in the amplitude of light-evoked electrical responses of 6.5% per degree and caused changes in both O2 consumption and glycolysis of 6.8% per degree (Q10 = 1.9). A surprisingly large fraction of oxidative energy, corresponding to about 40% of the total energy generated, could not be assigned to phototransduction, to neurotransmission, to Na+ transport for other purposes, or to vegetative metabolism. We cannot account for its usage, but it may be related to the (previously reported) rapid turnover of the gamma-phosphate of retinal GTP, the function of which also remains unknown.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1312137 TI - Demonstration of coexisting catecholamine (dopamine), amino acid (GABA), and peptide (NPY) involved in inhibition of melanotrope cell activity in Xenopus laevis: a quantitative ultrastructural, freeze-substitution immunocytochemical study. AB - This quantitative ultrastructural immunocytochemical study demonstrates the coexistence of a catecholamine [dopamine (DA)], an amino acid (GABA), and a neuropeptide [neuropeptide Y (NPY)] in axon varicosities innervating the pars intermedia of Xenopus laevis. The varicosities are assumed to control the pars intermedia melanotrope cells, which regulate skin color during the physiological process of background adaptation. Varicosity profiles appear to abut melanotrope cells and folliculostellate cells, star-shaped cells that intimately contact the melanotropes. All varicosity profiles contain two morphological types of vesicle. Monolabeling studies on routinely fixed and freeze-substituted tissues showed that the small, electron-lucent vesicles store GABA, whereas DA and NPY occur in larger, electron-dense ones. Double and triple labeling experiments, in which the degree of immunoreactivity was quantified per varicosity profile and per vesicle, led to the conclusion that (1) DA, GABA, and NPY coexist within almost all varicosity profiles and (2) DA and NPY are costored within electron-dense vesicles. Varicosity profiles that about melanotrope cells show a much higher ratio between the numbers of electron-lucent and electron-dense vesicles than varicosities contacting folliculostellate cells (15.8 and 3.3, respectively). This differential distribution is in line with the previous demonstration that, in contrast to GABA, NPY does not act directly on the melanotrope cells but indirectly, by controlling the activity of the folliculostellate cells. PMID- 1312138 TI - Calcium/calmodulin-activated phosphodiesterase expressed in olfactory receptor neurons. AB - We show that calmodulin-dependent phosphodiesterase (CAM-PDE) is selectively expressed in mature olfactory receptor neurons within the olfactory mucosa. Immunocytochemical staining reveals neuronal immunoreactivity that is most pronounced within cilia, dendritic knobs, and axon bundles. Neither sustentacular cells nor basal cells display immunoreactivity. The extent of loss of neuronal immunoreactivity following bulbectomy resembles loss of the neuronal population. High-affinity CAM-PDE activity in olfactory cilia is fivefold greater than in brain, when assayed at low micromolar cAMP. This activity is depleted in turbinates following bulbectomy. Olfactory mucosal PDE activity is composed of a minimum of two major forms. In the absence of Ca(2+), rolipram-sensitive PDE comprises 65% of total activity. Following stimulation by Ca2+, CAM-PDE activity is elevated sixfold to become the predominant form, thereby increasing total activity 300%, with half-maximal effect at 1 microM Ca2+. We propose that Ca2+ stimulation of CAM-PDE may be necessary for termination of olfactory signals. PMID- 1312139 TI - Spatiotemporal patterns of expression of NGF and the low-affinity NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis. AB - We show here that NGF and its low-affinity receptor (p75NGFR) are expressed during rat embryogenesis at sites that are known to have important roles in tissue morphogenesis and myogenesis. The developing skin of the maxilla, the mandible, and the limb showed very similar patterns of NGF and p75NGFR expression. However, NGF and p75NGFR expression in the developing limb initiated at the limb bud stage and was concentrated at proximal and distal developmental sites that have been reported to be involved in limb morphogenesis. Expression at the proximal/distal ends of the limb persisted throughout limb development, with some of the highest levels of expression occurring at the limb axillary sites, which were not highly innervated. We have also found p75NGFR expression at sites of mesenchymal/epithelial interactions in several developing organs that do not appear to have an adjacent source of NGF and may therefore be sites that bind and respond to the other members of the NGF family (brain-derived neurotrophic factor and neurotrophin-3). These organs include the lung, testes, and kidney, where expression of p75NGFR occurred during the morphogenesis of specific epithelial structures and was coexpressed with the cell adhesion molecule NCAM. In addition, we found that NGF and p75NGFR were expressed during myogenesis. p75NGFR was observed in myoblast cells expressing MyoD1, a myoblast differentiation marker, and NGF transcripts in cells just adjacent to the developing myoblasts. When the myoblasts differentiate into myotubes, p75NGFR and MyoD1 cease to be expressed and the adjacent cells concomitantly cease to be make NGF. However, NGF and p75NGFR were not present in the early muscle precursor cells of the myotome of the somites but were observed in the dermatome and sclerotome, respectively. These results suggest that NGF and p75NGFR have functional roles in developmental processes that affect morphogenesis and cell differentiation. PMID- 1312140 TI - Aberrant projection induced by otocyst removal maintains normal tonotopic organization in the chick cochlear nucleus. AB - Nucleus magnocellularis (NM), a second-order nucleus in the chick auditory system, is topographically and tonotopically organized. The basilar papilla (cochlea) projects onto the ipsilateral NM via the auditory nerve. The anteromedial region of NM is innervated by the proximal end of the basilar papilla and responds to high-frequency sounds; more posterolateral regions receive input from more distal locations along the papilla and respond to progressively lower frequencies. NM projects exclusively to the third-order neurons of nucleus laminaris (NL). Otocyst removal prevents the formation of the ipsilateral cochlea and cochlear nerve and results in the development of an aberrant functional projection from the contralateral NM to the "deafferented" NM on the operated side of the brain (Jackson and Parks, 1988). In the present experiment, the otocyst was removed unilaterally and the tonotopic organization of the deafferented NM was physiologically mapped at 17-18 d of embryonic age (E17-E18). Quantitative analyses revealed that the frequency organization of the deafferented NM is almost identical to that in normal embryos. Progressively higher characteristic frequencies were recorded at successively more anterior and more medial locations in the nucleus, and the orientation of the tonotopic axis was indistinguishable from normal. Furthermore, the correlation between characteristic frequency and anatomical location is comparable in the deafferented (r = 0.91) and normal (r = 0.87) NM. The only noticeable discrepancy is that characteristic frequencies in NM on both sides of the brain of operated embryos are higher than the frequencies observed previously at comparable regions of the nucleus in unoperated controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312141 TI - The effect of tumor necrosis factor-alpha on human malignant glial cells. AB - The influence of human recombinant tumor necrosis factor-alpha has been assessed on a cell line (U-251) derived from a human malignant glial tumor. The results of this study demonstrate that tumor necrosis factor-alpha at doses of 50 and 100 ng/ml: 1) did not have cytotoxic or cytostatic effects on the U-251 cell line; 2) significantly increased the intracellular activity of manganese superoxide dismutase but had no effect on copper and zinc superoxide dismutase, catalase, or glutathione peroxidase activity; and 3) did not significantly alter the intracellular or extracellular general protease and collagenase type IV activity of these cells. The resistance of the U-251 cell line to tumor necrosis factor alpha cytotoxicity may be related in part to the high intrinsic manganese superoxide dismutase activity present in this cell line combined with the ability of this cell line to induce substantial amounts of protective manganese superoxide dismutase activity in response to tumor necrosis factor-alpha. PMID- 1312142 TI - Developing national guidelines for nurse practitioner education: an overview of the product and the process. AB - In 1988, the National Organization of Nurse Practitioner Faculties appointed an ad hoc education committee (AHEC) to review existing nurse practitioner (NP) education curricula and to formulate national guidelines. An overview of the new NP guidelines are presented along with the philosophy, content, objectives, and competencies that are viewed as the foundation for NP education today. The guidelines are presented within the structure outlined in Brykczynski's (1985) research about NP practice. Thus, as a "product" of the Advanced Nursing Practice: Nurse Practitioner Curriculum Guidelines (NPCG), a new NP graduate for the 1990s could be described as one who demonstrates beginning competencies in primary health care theory and research within the five domains of practice identified by Brykczynski. PMID- 1312143 TI - Linking theory and practice in teaching basic nursing skills. AB - In an attempt to integrate theory and practice in baccalaureate nursing education, students were taught nursing skills with two cognitive strategies (Vee heuristics and concept maps) that consciously identify and reinforce connections between scientific theory and practice. The research showed that students using Vee heuristics and concept maps, rather than traditional modes, were significantly better able to identify scientific principles to describe why specific steps of a nursing skill were done. PMID- 1312144 TI - Use of clinical logs by beginning nursing students and faculty to identify learning needs. AB - Students entering a nursing program bring with them an increasing variety of life experiences. This study compares the learning needs of nontraditional and traditional nursing students during the first clinical experience. Twenty sophomore students wrote weekly reactions to their clinical experiences in the form of a log. The logs analyzed each week's clinical experience, assessed attainment of the week's goals, and identified goals for the following week. Descriptive analysis identified the following major themes and patterns of learning needs: learning from negative experiences, awareness of contextual influences, recognition of improved communication skills, identification of locus of motivation, and ability to conduct client teaching. Building on students' prior experiences can provide opportunities for self-reflection and promote the development of self-directed learning. PMID- 1312145 TI - Graduate home health education: a survey of home health educators and agency personnel. AB - To determine if there is a body of essential content that should be common to master's-level home care programs, a purposive sample of 200 nurses involved in home health or community health nursing was selected. The respondents (N = 118), including faculty and educational administrators (N = 61) and supervisors and administrators of home health agencies (N = 57), were asked their perceptions of the knowledge needed and their priorities for curriculum content for master's prepared home care specialists in both clinical and administrative roles. There was agreement in most content areas, but significant differences were found between faculty and agency personnel in their priorities for community health concepts, and in their evaluation of nursing theory and epidemiology as essential content in both roles. We believe these results have important implications for nurse educators. As schools prepare students for leadership roles in today's home care environment, it is critical that pertinent content be well integrated into the curriculum. PMID- 1312146 TI - Education as social responsibility. PMID- 1312147 TI - The relationship among multiple assessments of nursing education outcomes. AB - Three internal and three external outcome measures generated data for this longitudinal study. The internal outcome measures were nursing GPA, nonnursing GPA, and clinical evaluations of students during eight clinical rotations. The external evaluations were NCLEX scores, the graduates' self-rating of their competency in meeting program objectives, and their immediate supervisors' ratings on the identical competency rating scale. Data analyzed using Pearson correlation coefficients revealed significant correlations among all internal measures of academic outcomes with one external measure, the NCLEX score. There was no correlation between any nursing measure of outcome and the supervisor's ratings. There was a modest correlation between the supervisors' rating and the nonnursing GPA. The faculty clinical evaluation was the only significant correlation found between the alumni rankings and any other measure of outcome. There was no correlation between the supervisors' and the graduates' ratings. PMID- 1312148 TI - Educational specialist: grant-funded instructional and clinical support for minority and high-risk nursing students. PMID- 1312149 TI - Nursing theory made practical. PMID- 1312150 TI - Nursing in Saudi Arabia as perceived by university students and their parents. PMID- 1312151 TI - Sexual harassment in academia: legal and administrative challenges. AB - Guidelines and institutional policies regarding sexual harassment in academia have a relatively short and controversial background. Deference to Equal Employment Opportunity Commission (EEOC) guidelines in employment sexual harassment incidents guides much of the thinking in contemporary courts. Title IX of the Educational Amendments and the Civil Rights Restoration Act of 1987 are but two of the legal redresses available to students with harassment grievance complaints. Lack of definition of the term as well as research studies in nursing complicate the issue of sexual harassment. The potential impact of harassment on nursing students both in the classroom and in the practice area is significant. Nursing administrators and educators must be proactive in writing and implementing policies regarding sexual harassment. PMID- 1312152 TI - Mortality among dust-exposed Chinese mine and pottery workers. AB - A cohort study of approximately 68,000 persons employed during 1972 to 1974 at metal mines and pottery factories in south central China was conducted to evaluate mortality from cancer and other diseases among workers exposed to different levels of silica and other dusts. A follow-up of subjects through December 31, 1989 revealed 6,192 deaths, a number close to that expected based on Chinese national mortality rates. There was, however, a nearly 6-fold increase in deaths from pulmonary heart disease (standard mortality ratio, 581; 95% confidence interval 538 to 626), and a 48% excess of mortality from nonmalignant respiratory diseases (standard mortality ratio, 148; 95% confidence interval, 139 to 158), primarily because of a more than 30-fold excess of pneumoconiosis. Pulmonary heart disease and noncancerous respiratory disease rates rose in proportion to dust exposure. Cancer mortality overall was not increased among the miners or pottery workers. There was no increased risk of lung cancer, except among tin miners, and trends in risk of this cancer with increasing level of dust exposure were not significant. Risks of lung cancer were 22% higher among workers with than without silicosis. The findings indicate that respiratory disease continues to be an occupational hazard among Chinese miners and pottery workers, but that cancer risks are not as yet strongly associated with work in these dusty trades. PMID- 1312153 TI - Attention deficit hyperactivity disorder in children: diagnosis, treatment, and follow-up. AB - Hyperactive, and fidgeting behavior in children, is not a new syndrome, but has been present in children for centuries. Only in recent years have health providers begun to observe these features and behaviors in children and recommend some therapies. Children labeled with Attention Deficit Hyperactivity Disorder (ADHD) display the symptoms of inattention, impulsivity, and hyperactivity; however, these behaviors are seen in a variety of conditions. This article describes some of the symptoms associated with ADHD, as well as the evaluation, therapeutic modalities (behavioral, psychodynamic and pharmacological), and the follow-up of children with ADHD. PMID- 1312154 TI - MMPI profiles of women in codependency treatment. AB - The Minnesota Multiphasic Personality Inventory (MMPI) profiles of 73 women presenting themselves for treatment of codependency in a 10-day residential setting were examined. Results suggest a significant amount of psychopathology to be present in this population. More than 50% of these individuals produced clinically significant elevations of five or more scales, and 38% produced elevations on six or more scales. PMID- 1312155 TI - MCMI differences between alcoholics and cocaine abusers: effect of age, sex, and race. AB - Samples of alcohol-dependent-only subjects (n = 164), cocaine-dependent-only subjects (n = 63), and subjects dependent on multiple substances, including alcohol and cocaine (n = 103), were administered the Millon Clinical Multiaxial Inventory (MCMI) as part of a routine clinical evaluation. The alcohol-only group was older (M = 38.7 years) and had a higher percentage of White subjects than other groups. The multiple-use (60%) group also had a higher percentage of White subjects than the cocaine only group (38%) and a higher percentage of male subjects (81%) than the alcohol-only group (67%). Although the MCMI characteristics of each diagnostic group paralleled previous findings, few MCMI differences were found after controlling for age, sex, and race effects. The implications of these results for treatment development are discussed. PMID- 1312156 TI - Gastrointestinal motor alterations induced by precipitated benzodiazepine withdrawal in rats. AB - The effects of benzodiazepine withdrawal on intestinal motor activity and propulsion were investigated in two groups of diazepam-dependent rats (15 mg/kg/day for 8 days). Withdrawal was precipitated by injection of two benzodiazepine antagonists (Ro 15.1788 and PK 11.95) acting on central and peripheral-type receptors, respectively. Intestinal motor activity was assessed by implanting electrodes for long-term electromyographic recordings. Gastrointestinal transit was evaluated after gavage by a marker (51CrO4Na2) and radioactivity counting. Both RO 15.1788 (15 mg/kg) and PK 11.195 (5 mg/kg) triggered an abstinence syndrome with behavioral and autonomic signs. At the intestinal level, Ro 15.1788 induced a phase of strong irregular spiking activity (173 +/- 63 min) which remained located in the duodenum. In contrast, PK 11.195 induced a period of propagated myoelectric complexes characterized by phases II and III of high amplitude. The cecal frequency was doubled during the 1st hr after withdrawal induced by the two antagonists. Both Ro 15.1788 and PK 11.195 at this dosage had no effect per se on intestinal motility in vehicle-treated rats. In the second group of rats, gastric emptying was enhanced by 49.4 and 45.6% by Ro 15.1788 and PK 11.195, respectively. In contrast, PK 11.195 was able to accelerate the intestinal transit more than did Ro 15.1788 (geometric center, 5.9 +/- 0.43 and 5.3 +/- 0.49, respectively, vs. 4.1 +/- 0.31 in control rats). Our study shows that precipitated benzodiazepine withdrawal in diazepam-dependent rats induces alterations of the intestinal myoelectrical activity leading to an increase of the gastrointestinal transit. Central and peripheral-type receptors are involved in these effects. PMID- 1312157 TI - The effect of sensory nerve depletion on cholinergic neurotransmission in guinea pig airways. AB - C-fiber primary afferent sensory nerves, containing neuropeptides such as substance P and neurokinin A, mediate excitatory nonadrenergic, noncholinergic (e NANC) bronchoconstrictor responses in guinea pigs. We have studied the effects of sensory nerve depletion in vivo and at four different airway levels in vitro. Capsaicin pretreatment significantly reduced the cholinergic responses to electrical field stimulation at all airway levels studied when compared to similar responses obtained in tissues from both untreated animals and animals treated with the vehicle for capsaicin (at 8 Hz, 27.2 +/- 4.9% of maximal contraction to 10(-2) M acetylcholine in lower trachea from vehicle-pretreated animals compared with 11.6 +/- 2.9% in lower trachea from capsaicin-pretreated animals, P less than .01). Stimulation of lower tracheal segments at 30-min intervals revealed a cholinergic response which was followed by a small, delayed e-NANC component. In vivo cholinergic bronchoconstrictor responses to vagal stimulation were also significantly diminished (at 5 Hz from 11.6 +/- 2.2 cm H2O in vehicle-pretreated animals to 3.3 +/- 1.4 cm H2O in capsaicin-pretreated animals). Bronchoconstrictor responses to acetylcholine or substance P in normal, vehicle-pretreated or capsaicin-pretreated animals were not significantly different either in vitro or in vivo. Sensory neuropeptides released from C-fiber afferent nerves may facilitate cholinergic neurotransmission in airways. This effect appears more marked at airway levels in which e-NANC responses are demonstrable. PMID- 1312158 TI - Characterization of the contractile serotonergic receptor in guinea pig trachea with agonists and antagonists. AB - 5-Hydroxytryptamine (5-HT)2 receptors can be partially characterized by their sensitivity to ketanserin blockade and increase in phosphoinositide turnover upon stimulation. Previously, the contraction of guinea pig trachea to 5-HT was shown to be antagonized by the 5-HT2 receptor antagonists ketanserin and LY53857. However, 5-HT did not dramatically increase phosphoinositide turnover in guinea pig trachea, suggesting that the contractile receptor may be different from the classically defined 5-HT2 receptor. The present in vitro studies better characterize this receptor, using diverse serotonergic agonists and antagonists to profile in more detail the contractile serotonergic receptor in guinea pig trachea. With regard to agonists, the 5-HT2 receptor agonists DOI and alpha methyl-5-HT contracted guinea pig trachea with greater potency than quipazine, 5 methoxytryptamine, 5-carboxamidotryptamine, 8-hydroxy-2-(di-N propylamino)tetralin and 2-methyl-5-HT. Sumatriptan and 1-(3-chlorophenyl) piperazine (10 nM-100 microM) were inactive as agonists. A strong correlation between agonist potency (EC50) and reported 5-HT receptor binding affinities was found for both the 5-HT1C (r = 0.890) and 5-HT2 (r = 0.831) receptor. Ketanserin, spiperone, ritanserin, LY53857, 1-napthylpiperazine, 1-(3-chlorophenyl) piperazine, rauwolscine, ICS 205-930, cyanopindolol and sumatriptan all blocked 5 HT-induced contractions in guinea pig trachea. As occurred with agonist potencies, strong correlations were found between reported 5-HT1C (r = 0.814) and 5-HT2 (r = 0.912) receptor binding affinities in brain membranes and apparent dissociation constants (KB) for the 10 antagonists of 5-HT induced contraction in guinea pig trachea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312159 TI - Neurally mediated relaxation of opossum internal anal sphincter: influence of superoxide anion generator and the scavenger. AB - The present investigation was undertaken to examine the influence of super oxide anion generator hydroquinone and the superoxide anion scavenger superoxide dismutase (SOD) on the neurally mediated relaxation of the internal and sphincter (IAS). The studies were performed in vitro on IAS smooth muscle strips of opossums. Neural stimulation with appropriate parameters of electrical field stimulation is known to cause IAS relaxation by the activation of nonadrenergic noncholinergic inhibitory neurons. Hydroquinone caused a concentration-dependent suppression of IAS relaxation in response to neural stimulation. The suppression of the IAS relaxation was reversed by SOD in a concentration-dependent manner. The fall in the IAS tension by nitric oxide (NO) was also suppressed by hydroquinone and reversed by SOD. SOD alone caused an augmentation of the fall in the IAS tension by NO. The fall in the IAS tension in response to the candidate inhibitory neurotransmitter vasoactive intestinal polypeptide was not modified by SOD in the basal state. Hydroquinone, however, caused a significant suppression of vasoactive intestinal polypeptide-induced fall in the IAS tension which was reversed by SOD. The fall in the resting IAS tension by the directly acting smooth muscle relaxants, beta adrenoceptor agonist isoproterenol and atrial natriuretic factor were not significantly modified by hydroquinone or SOD. From the present data we conclude: NO or an NO-like factor plays a significant role in the nonadrenergic noncholinergic nerve-mediated IAS relaxation. PMID- 1312160 TI - Prostaglandin E1-induced vasorelaxation in porcine coronary arteries. AB - The mechanism of prostaglandin E1 (PGE1)-induced vasorelaxation was studied in the porcine left anterior descending artery (diameter = 2.0-3.0 mm) and its branches (diameter = 0.6-1.0 mm). In the large coronary arteries, PGE1 increased the basal tone at concentrations from 10(-8) to 3 x 10(-7) M and decreased the tone at concentrations above 3 x 10(-7) M. However, in the small coronary arteries, PGE1 did not affect the basal tone at concentrations below 3 x 10(-6) M and evoked only relaxation at above 10(-5) M. PGE1 caused dose-dependent relaxation of vessels previously contracted by prostaglandin F2 alpha or endothelin-1 at concentrations above 10(-7) M in large coronary arteries and above 10(-8) M in small coronary arteries. Removal of the endothelium did not influence the relaxant response to PGE1 of either type of artery. In addition, 10(-4) M aspirin did not influence the PGE1-induced vasorelaxation of large and small coronary arteries. However, treatment with 5 x 10(-6) M ouabain or partial replacement of Na+ with Li+ (Na+ concentration, 25 mEq/l) significantly attenuated the relaxant response to PGE1 in large and small coronary arteries. These results indicate that the responsiveness of large and small coronary arteries to PGE1 differs in the pig and that the electrogenic Na+ pump has a primary role in the relaxant effect of PGE1 on both small and large arteries. PMID- 1312161 TI - Pharmacological evaluation of JO 1870: relation to the potential treatment of urinary bladder incontinence. AB - The effect of p.o. administered JO 1870 [(-)-1-(p-chlorophenyl)-N,N- dimethyl-1 ethyl(4-phenyl)-but-3-en-1-ylamine, hydrochloride] on the urinary bladder cystometrogram has been investigated in the unanesthetized rat. The effects of JO 1870 have been compared with those of morphine and reference drugs currently used for the treatment of urinary incontinence in humans. JO 1870 (2.5-25 mg/kg) dose dependently increased the bladder capacity and the threshold pressure responsible for urination. These effects were antagonized by the i.v. administration of naloxone (0.2 mg/kg). In comparison, morphine (2.5-25 mg/kg) moderately increased urinary volume and threshold pressure. Different anticholinergic drugs (propantheline bromide, 10 mg/kg; terodiline, 25 mg/kg; dicyclomine, 25 mg/kg) had no significant effects on either parameter and the antidepressant clomipramine (25 mg/kg) decreased both. In vitro, JO 1870 specifically displaced [3H]-[D-Ala2,MePhe4,Gly5-(ol)]enkephalin from binding sites in guinea pig whole brain membranes and rat thalamus; the sodium shift ratio obtained from [3H]naloxone binding was 16. These results suggest that JO 1870 has some opioid agonist activity. JO 1870 (2.5-300 mg/kg) had few effects on cardiorespiratory, gastrointestinal or nociceptive systems in rats. Together, these results indicate that JO 1870 is a nonanticholinergic agent that potently increases bladder capacity, likely through an opioid mechanism, and may have potential use in the treatment of urinary incontinence. PMID- 1312162 TI - Zolpidem behavioral pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal. AB - This study examined in baboons various behavioral effects of zolpidem, a short acting imidazopyridine hypnotic which has selectivity for subtypes of the benzodiazepine receptor. Intravenous drug self-injection was studied under a fixed-ratio 80- or 160-response schedule with a 3-hr timeout after each injection. Maximal rates of self-injection maintained by zolpidem (0.01-1 mg/kg) were consistently higher than those maintained by vehicle and the benzodiazepine hypnotic triazolam. Substitution of vehicle after about 2 weeks of zolpidem self injection (7-8 mg/kg/day) resulted in a time-limited suppression of food pellet intake, indicating a drug withdrawal effect. In a drug discrimination study, baboons were trained to discriminate either lorazepam (1.8 mg/kg p.o.) or pentobarbital (10 mg/kg p.o.) from the no-drug condition. Zolpidem (0.1-18 mg/kg p.o.) occasioned both lorazepam- and pentobarbital-appropriate responding (greater than 80%) in a dose-dependent manner. In a final experiment, zolpidem (3.2 or 5.6 mg/kg i.m.) produced ataxia and sedation that progressively decreased over 7 consecutive days of administration. The withdrawal, discriminative stimulus effects and tolerance shown with zolpidem were similar to those shown previously with benzodiazepines under similar conditions. The rates of self injection of zolpidem were similar to those maintained by intermediate duration barbiturates (e.g., pentobarbital) and higher than those maintained by 11 benzodiazepines studied previously under similar conditions. Further research on the reinforcing effects of zolpidem may provide useful insights into mechanisms underlying the maintenance of behavior by compounds acting through the benzodiazepine receptor. PMID- 1312163 TI - Effects of ketamine on sensory perception: evidence for a role of N-methyl-D aspartate receptors. AB - The chiral forms of ketamine were applied as probes for N-methyl-D-aspartate receptor-mediated neurotransmission in humans. Both enantiomers, in clinically relevant concentrations, displaced [3H]dizocilpine (MK 801) from specific binding sites (phencyclidine sites) in membrane fractions of brain homogenates. (S) Ketamine was at least 4 times as potent as (R)-ketamine in this respect. In healthy volunteers, the most obvious effect of subanesthetic doses of both enantiomers was altered sensory perception. (S)-Ketamine was 4 times as potent as (R)-ketamine in reducing pain perception and in causing auditory and visual disturbances. Both enantiomers caused proprioceptive disturbances (feelings of detachment from the body) and slightly reduced the ability to recall objects seen after administration of the drugs. The ability to recall objects seen immediately before drug exposure was unaffected. The results are in accordance with the hypothesis that inhibition of sensory perception by ketamine in subanesthetic concentrations is due to N-methyl-D-aspartate receptor blockade. It is suggested that N-methyl-D-aspartate receptor-mediated transmission is involved in the processing of sensory information in the human brain. PMID- 1312164 TI - Extremely long-lasting antagonistic actions of nor-binaltorphimine (nor-BNI) in the mouse tail-flick test. AB - The duration of antagonistic action of nor-binaltorphimine (nor-BNI), a kappa antagonist, of antinociception resulting from selective opioid agonists, was examined using the mouse tail-flick assay as the endpoint. Nor-BNI (1 nmol, i.c.v. at -20 min) antagonized equiantinociceptive doses of the opioid kappa agonists (5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl) benzeneacetamide (U69,593) (70 nmol i.c.v.) or bremazocine (25 nmol i.c.v.), but did not antagonize antinociception produced by the mu opioid selective [D-Ala2, NMePhe4, Gly-ol]enkephalin or the delta opioid-selective [D Pen2, D-Pen5]enkephalin. Pretreatment with nor-BNI (1 nmol i.c.v.) antagonized the antinociceptive effects of U69,593 and bremazocine for up to 28 days. At all pretreatment times, the antinociceptive dose-response lines for these kappa agonists were displaced to the right to various degrees in a parallel fashion; an increasing rightward displacement of the U69,593 and bremazocine antinociceptive dose-response lines was observed at 1 and 3 days after a single nor-BNI pretreatment, with a gradual return toward the control level at later times after pretreatment. Increasing the dose of nor-BNI to 10 nmol produced only a transient blockade of equiantinociceptive doses of the mu selective agonist [D-Ala2, NMePhe4, Gly-ol]enkephalin and the delta selective agonist [D-Pen2, D Pen5]enkephalin (at 20-30 min post-nor-BNI pretreatment).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312166 TI - Low-level N-methyl-D-aspartate receptor activation provides a purinergic inhibitory threshold against further N-methyl-D-aspartate-mediated neurotransmission in the cortex. AB - N-methyl-D-aspartate (NMDA) is 33 times more potent at releasing adenosine than it is at releasing [3H]norepinephrine from slices of rat parietal cortex. Consequently, maximal adenosine release occurs at levels of NMDA receptor activation which release little norepinephrine. The potential modulatory role of the adenosine released during NMDA receptor activation on NMDA-evoked [3H]norepinephrine release was investigated. The A1-selective agonist R-(-)N6-(2 phenylisopropyl)adenosine (10 microM) decreased 100 microM NMDA-evoked [3H]norepinephrine release by 27%; this was reversed by the P1 antagonist 8 phenyltheophylline (8-PT, 10 microM), indicating that NMDA-evoked norepinephrine release from cortical slices is susceptible to purinergic modulation. On the other hand, 8-PT had no effect on [3H]norepinephrine release evoked by 100 microM NMDA, suggesting that endogenous adenosine, released during NMDA receptor activation, does not modulate [3H]norepinephrine release. However, [3H]norepinephrine release precedes adenosine release, so that the released adenosine may not be temporally available to modulate [3H]norepinephrine release. Pretreatment with a concentration of NMDA (10 microM) which releases substantial endogenous adenosine, but very little [3H]norepinephrine decreased subsequent 100 microM NMDA-evoked [3H]norepinephrine release by 52%. 8-PT partially reversed this inhibition, indicating that prereleased adenosine, acting at P1 purinoceptors, modulated subsequent NMDA-evoked [3H]norepinephrine release. These results suggest that adenosine, released during submaximal NMDA receptor activation, may provide an inhibitory threshold which must be overcome in order for other NMDA-mediated processes to proceed maximally. PMID- 1312165 TI - Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline. AB - Myocardial ischemia and reperfusion cause coronary vascular injury involving both the large epicardial arteries and the microcirculation. Although the mechanisms are unclear, leukocytes appear to play an important role. Since the methylxanthine derivative pentoxifylline (PTX) decreases neutrophil activity in vitro, we hypothesized that it might diminish coronary vascular injury due to ischemia and reperfusion. We investigated the effects of PTX on coronary microvascular and epicardial artery injury in open chest, anesthetized dogs undergoing moderate (60 min) or more prolonged (90 min) ischemia due to left anterior descending coronary artery occlusion followed by 60 min of reperfusion. As an index of microvascular injury, we assessed regional permeability with a dual radioisotope protein leak index (PLI) method. Both ischemic periods with reperfusion increased the PLI of severely ischemic (flow less than or equal to 20/ml/min/100 g) myocardium by 2.5- and 3-fold, respectively, compared to nonischemic (flow greater than or equal to 100 ml/min/100 g) myocardium. Treated dogs received PTX (20 mg/kg bolus plus 0.1 mg/kg/min infusion) before ischemia. PTX reduced the increase in the PLI by 40% after 60 min of ischemia (PLI = 5.87 +/- 0.48 vs. 4.10 +/- 0.52 untreated vs. PTX-treated; P less than .05), and by 25% after 90 min of ischemia (6.84 +/- 0.49 vs. 4.84 +/- 0.42; P less than .05). The amount of protein leak was inversely related to ischemic blood flow, and the magnitude of this relationship was significantly reduced in PTX-treated animals. In arterial rings from untreated dogs exposed to 90 min of ischemia followed by reperfusion, there was impaired relaxation to ADP and acetylcholine, but not to sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312167 TI - Stimulant effects of muscarinic agonists in embryonic chick ventricular muscle. Are the effects mediated by protein kinase C? AB - Muscarinic agonists at high concentrations produce stimulant effects in the heart. We used the embryonic chick ventricle, in which muscarinic receptor activation markedly increases phosphoinositide (PI) breakdown, to investigate the possibility that receptor-induced PI metabolism mediates the stimulant effects. In preparations paced at 0.5 to 1 Hz, carbachol (CCh; 10(-6) to 10(-3) M) shifted the action potential plateau to more positive potentials and markedly prolonged the action potential duration (APD). These effects were not associated with a change in the resting potential, did not fade with time and could be obtained in the presence of propranolol (3 x 10(-7) M) or tetrodotoxin (10(-6) M). The same effects could be obtained with acetylcholine or oxotremorine (10(-4) M) and could be suppressed with atropine (0.9 x 10(-6) M). The sensitivity of the APD to muscarinic agonists was high during early embryonic stages and declined rapidly with age. At days 3 to 5, the APD was prolonged in the presence of CCh by greater than 80% of its control value. After day 12, CCh had no prolonging effect on the APD. In nonpaced preparations, the agonist depolarized the membrane and/or induced automaticity in quiescent preparations. When automaticity was present, spontaneously or after addition of Ba++, the frequency of the automatic activity was increased by the agonist. These effects on resting potential and automaticity were also less marked in older embryos. CCh (10(-6) to 10(-4) M) evoked an atropine-sensitive positive inotropic effect in paced ventricular tissues in the presence of propranolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312169 TI - Reversal of desipramine toxicity in rats using drug-specific antibody Fab' fragment: effects on hypotension and interaction with sodium bicarbonate. AB - The effect of drug-specific antibody Fab' fragment on desipramine (DMI) toxicity was studied in anesthetized rats to determine 1) whether DMI-induced hypotension can be reversed, and 2) whether the effect of this Fab' fragment can be enhanced by the concurrent administration of hypertonic NaHCO3. DMI (60 mg/kg) was administered i.p. to produce marked hypotension. Antitricyclic antidepressant (TCA) Fab' (molar Fab'/DMI ratio = 0.11) or control Fab' was administered 15 min later as a 10 min i.v. infusion. The mean arterial pressure was higher at the end of anti-TCA Fab' infusion than after control Fab' (58 +/- 8 vs. 17 +/- 7 mm Hg, P less than .001). In a second protocol, DMI (30 mg/kg) was administered to prolong QRS duration. Anti-TCA Fab' alone (molar Fab'/DMI ratio = 0.09) and NaHCO3 alone both reduced QRS prolongation compared to control treatment, and combined therapy was more effective than either one alone. In both protocols, anti-TCA Fab' markedly increased the total DMI concentration and the bound fraction of DMI in serum, but did not alter the unbound DMI concentration. In the low DMI dose protocol, anti-TCA Fab' also reduced the cardiac DMI concentration. Concurrent treatment with anti-TCA Fab' and NaHCO3 substantially increased urinary DMI and anti-TCA Fab' excretion compared to treatment with anti-TCA Fab' alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312168 TI - Effects of repetitive administration of recombinant human interleukin-1 beta, an analog or corticotropin-releasing hormone combined with lysine vasopressin on rats with glucocorticoid-induced secondary adrenocortical insufficiency. AB - We investigated effects of corticotropin-releasing hormone (CRH), lysine vasopressin and interleukin (IL)-1 beta[1-148], a less pyrogenic analog of human IL-1 beta, on the hypothalamo-pituitary-adrenal axis in a rat model of secondary adrenocortical insufficiency. After 2 weeks of corticosterone 21-sodium succinate treatment, hypothalamic CRH, anterior pituitary adrenocorticotropic hormone (ACTH) and the adrenal weight of the rats decreased significantly and their plasma ACTH showed a significantly smaller response to ether stress, as did plasma corticosterone level. A mixed solution of CRH (10 micrograms) and lysine vasopressin (2 micrograms) or recombinant human IL-1 beta[1-148] (1 micrograms), administered to these rats for 7 days, apparently accelerated the recovery of the pituitary and adrenocortical responsiveness to ether stress and significantly increased the recovery rate of anterior pituitary ACTH contents and adrenal weight. The IL-1 beta analog also increased hypothalamic CRH. These data indicated that, in a rat model with glucocorticoid-induced adrenocortical insufficiency, synthesis and release of hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid were all considerably affected. CRH combined with lysine vasopressin or a less pyrogenic IL-1 beta analog, when administered to these rats, accelerated the recovery of the pituitary and the adrenocortical functions significantly, suggesting the potential clinical usefulness of these peptides. PMID- 1312170 TI - Dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium analogs in cultured neurons: relationship to the dopamine uptake system and inhibition of mitochondrial respiration. AB - Several analogs of 1-methyl-4-phenylpyridinium (MPP+) were evaluated for their affinity for the dopamine uptake system and their ability to inhibit NADH dehydrogenase (complex I) of the mitochondrial electron-transport chain. Moreover, these compounds were tested for their ability to cause selective dopaminergic neurotoxicity in cultured mesencephalic neurons. Simultaneous [3H]dopamine and gamma-amino-[14C]butyric acid uptake and immunocytochemical techniques were used as indices of neuronal damage in cultured cells. The compounds that were potent and selective dopaminergic neurotoxins had high affinity for the dopamine transport system, as measured by their ability to cause dopamine release, and were similar to MPP+ in inhibiting mitochondrial respiration. One compound (1-methyl-4-phenylpyrimidinium) had high affinity for the dopamine uptake system but was a weak inhibitor of mitochondrial respiration and, accordingly, was not neurotoxic. The 4'-alkylated analogs of MPP+, which were poor substrates for the dopamine uptake system and extremely potent inhibitors of mitochondrial respiration, caused a nonselective damage of neurons in culture. Analogs that were not substrates for the dopamine carrier and not inhibitors of mitochondrial respiration were not neurotoxic. This study describes the neurotoxicity of a number of analogs of MPP+ and highlights the importance of the dopamine uptake system and the ability to inhibit mitochondrial respiration as critical processes in conferring selectivity and neurotoxicity, respectively, to MPP+ and analogs, for dopaminergic neurons in culture. PMID- 1312171 TI - Inhibition of protein phosphorylation by opioid-inhibited adenylyl cyclase in rat brain membranes. AB - Opioid inhibition of adenylyl cyclase is a major second messenger system associated with opioid receptors in brain. To identify membrane phosphoproteins whose phosphorylation state is modulated by opioid inhibition of adenylyl cyclase, rat striatal membranes were preincubated with opioid agonists in the presence of 500 microM 5'-adenylyl-imidodiphosphate (which acted as a substrate for adenylyl cyclase, but not for protein kinase) before addition of [gamma 32P]ATP. Under these conditions, adenylyl cyclase in the membranes formed cyclic AMP, which stimulated cyclic AMP-dependent protein kinase. This process was confirmed by observing forskolin-stimulated phosphorylation of two bands of MW 85 and 63 kDa, which were also stimulated directly by cyclic AMP. Forskolin stimulated phosphorylation of these two bands was inhibited by 15 to 30% by opioid agonists such as D-Ala2-Met5-enkephalinamide. This inhibition of phosphorylation was mediated by opioid receptors, because it required both sodium and GTP, and was blocked by naloxone. These results suggest that these two proteins may be primary targets of opioid-inhibited adenylyl cyclase in striatal membranes. PMID- 1312172 TI - Evaluation of LY203647 on cardiovascular leukotriene D4 receptors and myocardial reperfusion injury. AB - In vitro studies have shown LY203647 to be a selective antagonist of contractile responses to leukotriene (LT) D4 and LTE4 in guinea pig ileum, trachea and lung parenchyma. In pithed rat, i.v. injection of LTD4 produced pressor responses that were selectively antagonized by LY203647 in a dose-dependent manner [ED50 7.5 (6.0-9.5) mg/kg, i.v.]. In normal anesthetized rats and dogs, LTD4 reduced aortic blood flow and stroke volume in association with systemic vasoconstriction, variable blood pressure responses and no change in cardiac rate. LTD4 did not alter myocardial contractility corrected for alterations in afterload. Pretreatment of rats and dogs with LY203647 (1-10 mg/kg, i.v.) produced dose related inhibition of the myocardial and systemic hemodynamic effects of LTD4, whereas coadministration of LY203647 reversed established myocardial depression and systemic and pulmonary vasoconstriction during continuous infusion of LTD4 in dogs. LY203647 (10 mg/kg over 90 min, i.v.) infusion in normal dogs abolished or greatly antagonized hemodynamic responses to LTD4 for 6 hr. In subsequent experiments, myocardial infarct size was measured after 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion. LY203647 (10 mg/kg over 90 min, i.v.) treatment did not alter cardiovascular parameters when compared to time-related alterations observed in control dogs. ST segment deviation and the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion also were similar between groups. Resultant infarct sizes were 46 +/- 1 and 45 +/- 1% of the left ventricular mass placed at risk in control and LY203647-treated dogs, respectively. Present data illustrate the prominent cardiac and systemic hemodynamic effects of LTD4 and indicate that LY203647 produces selective and sustained antagonism of cardiovascular LTD4 receptors. Lack of containment of infarction by LY203647 suggests that endogenous cysteinyl-LT do not contribute to reperfusion injury of ischemic myocardium. PMID- 1312174 TI - [Treatment of small hepatocellular carcinoma by percutaneous injection of ethanol]. PMID- 1312173 TI - High-affinity dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1 propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine. AB - Dextromethorphan (DM) binds to high- and low-affinity sites in the rat brain. The high-affinity DM binding is inhibited by nonnarcotic antitussives, opipramol and sigma ligands with nanomolar affinities. Computer-assisted modeling of homologous and heterologous competition studies between DM and (+)-3-(3-hydroxyphenyl)-N-(1 propyl)piperidine [(+)-3-PPP] were performed at pH 8.4. These experiments confirmed the existence of the common high-affinity DM1/sigma 1 site (R1) for which DM and (+)-3-PPP have Kd values of 20 and 10 nM, respectively. DM also binds to a second high-affinity site (R2, Kd, 20 nM) for which (+)-3-PPP has only micromolar affinity. Similarly, (+)-3-PPP binds to another high-affinity site (R3, Kd, 60 nM) for which DM has micromolar affinity. The common high-affinity DM1/sigma 1 site is allosterically modulated by the anticonvulsant ropizine, and is (+)-pentazocine sensitive, as is the homologous site in the guinea pig. However, in the rat the common DM1/sigma 1 site is 10 times smaller than in the guinea pig. This explains the apparently different effects of the allosteric modifiers in both species. The multiplicity of binding sites for DM and (+)-3-PPP resolved in this investigation will help to establish the physiological role and the pharmacological potential of the different sites. Meanwhile, the pharmacological effects of DM and sigma ligands cannot be summarily attributed to any particular binding site or receptor. This investigation also demonstrates that the use of multiple labeled and unlabeled ligands, combined with computer assisted modeling, is essential to resolve multiple binding sites with similar affinities and to characterize the complex effects of allosteric modifiers. PMID- 1312175 TI - Workshop on cancer epidemiology in Latin America and the Caribbean. PMID- 1312176 TI - Heterogeneity for allelic loss in human breast cancer. AB - BACKGROUND: Loss of heterozygosity (LOH) at specific chromosomal regions in the tumor cells implicates the presence of tumor suppressor genes. However, it is also possible for an LOH to be randomly acquired and irrelevant to tumor development. PURPOSE: To determine whether a particular LOH in human breast carcinomas represents a loss of tumor suppressor gene or merely a random loss, we analyzed untreated primary breast cancers for LOH. METHODS: Ninety-eight primary human breast cancers from previously untreated patients were analyzed for LOH at 12 chromosomal regions including five randomly selected regions and seven regions previously reported in other cancer types and/or breast cancers. RESULTS: The baseline incidence of LOH was five out of 124 tests (4%) using randomly selected probes on chromosomes 1p, 2p, 4p, 11q, and Xq. Incidences of LOH significantly greater than background were seen in the following chromosomal regions: 22q (10 of 26 cases, 38%); 18p (five of 24 cases, 21%); 17p (30 of 59 cases, 51%); 13q (five of 14 cases, 36%); 3p (13 of 28 cases, 46%); and 1q (18 of 70 cases, 26%). In contrast to previous reports, the incidence of LOH was not significantly different from background for 11p15. In all cases, results were the same for metastatic lymph nodes and primary tumors, suggesting that the losses occurred early in the malignant progression. In cases with LOH at more than one locus, the same DNA sample often varied in degree of signal reduction for the missing alleles. CONCLUSION: These observations indicate the presence of both intertumor and intratumor heterogeneity for LOH. PMID- 1312177 TI - Levamisole potentiation of fluorouracil antiproliferative activity mimicked by orthovanadate, an inhibitor of tyrosine phosphatase. AB - BACKGROUND: Levamisole is an effective antihelminthic drug with immunomodulatory and anticancer activities in model systems. Combined with fluorouracil (5-FU) as adjuvant treatment following resection of Dukes' stage C colon carcinomas, levamisole significantly reduces mortality. However, neither 5-FU nor levamisole alone has a significant effect on survival in this patient group. Previously, we noted that in vitro levamisole potentiated the antiproliferative activity of 5 FU. PURPOSE: Because levamisole is known to inhibit alkaline phosphatases and has been reported to inhibit dephosphorylation of some membrane phosphoproteins, we studied the effects of levamisole analogues and of chemically unrelated inhibitors of phosphatases for their ability to potentiate 5-FU inhibition of tumor cell line proliferation in vitro. METHODS: Human cancer cell lines were exposed to drugs alone or in combination with 5-FU. Antiproliferative activity was measured by determining the extent of reduction of colony formation by the cell lines in test plates compared with control plates. RESULTS: We found that potentiation of 5-FU cytotoxicity by levamisole and by p-hydroxytetramisole, a metabolite of levamisole, is mimicked by orthovanadate, an inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor of serine and threonine phosphatases, Furthermore, l-p-bromotetramisole, a synthetic analogue of levamisole that is 10-fold more potent in inhibition of alkaline phosphatase than levamisole, potentiates the antiproliferative activity of 5-FU to a greater extent than d-p-bromotetramisole, a stereoisomer of l-p-bromotetramisole with little antiphosphatase activity. CONCLUSION: Inhibition of tyrosine phosphatases may be responsible for the potentiation by levamisole of the inhibitory activity of 5-FU in vitro. IMPLICATIONS: Inhibition of dephosphorylation of regulatory phosphoproteins may be related to the therapeutic efficacy of the combination of levamisole and 5-FU in the adjuvant treatment of colon carcinoma and may underlie at least some of the multiple effects of levamisole on immune parameters. PMID- 1312178 TI - Stimulation of growth by both androgen and estrogen of the EMP-K1 transplantable tumor with androgen and estrogen receptors from human extramammary Paget's disease in nude mice. AB - BACKGROUND: Experimental approaches using transplantable human tumors in nude mice have greatly improved studies on their pathogenesis and treatment. PURPOSE: We studied the establishment of a transplantable tumor, EMP-K1, derived from extramammary Paget's disease and the morphology and unique hormone dependence of this tumor. METHODS: Tissue fragments from a metastatic skin tumor of an 80-year old man with primary genital extramammary Paget's disease were implanted into male nude BALB/c mice. Tissue fragments of the established tumor were implanted into 50 castrated male 8-week-old nude mice, which were given injections of 100 micrograms testosterone propionate (TP), 100 micrograms 5 alpha dihydrotestosterone (DHT), 10 micrograms diethylstilbestrol (DES), or 1, 10, or 100 micrograms 17 beta-estradiol (E2). All injections were administered intramuscularly once daily, starting from the day of transplantation. The established tumors were examined immunohistochemically and biochemically. RESULTS: A transplantable tumor (EMP-K1) was established in the nude mouse. EMP K1 tumor cells expressed antigens such as carcinoembryonic antigen and epithelial membrane antigen, cytokeratin, and c-erbB-2 protein and contained androgen, estrogen, and progesterone receptors. The growth of the EMP-K1 tumor was stimulated by TP, DHT, DES, and E2. CONCLUSIONS: These results suggest that both androgen and estrogen may stimulate the growth of the same tumor by both androgen receptor and estrogen receptor pathways. IMPLICATIONS: The EMP-K1 tumor is a useful tool for studies on the biology of extramammary Paget's disease, and further studies using these tumors will provide useful information concerning proper hormone therapy. PMID- 1312179 TI - [Splenic lymphoma of Ki-1 positive B-cell type treated with CHOP]. AB - A 75-year old man was admitted to our hospital by complaining of his left supraclavicular lymphadenopathy. Physical examination also revealed splenomegaly and cervical lymphadenopathy. An abdominal CT scan showed paraaortic lymphadenopathy and splenomegaly with multiple low density area. A pathological diagnosis of Ki-1 lymphoma was made by the biopsied supraclavicular lymph node because the node consists of large cells with clear cytoplasms and conspicuous nucleoli and large cells were positive for IgM, lambda, CD20 and CD30 (Ki-1). The primary lesion of lymphoma was suspected to be spleen because of the radiological finding of the spleen. The patient responded to systemic chemotherapy (CHOP) with complete remission. Pathological and clinical characteristics of this B-cell Ki-1 lymphoma were discussed. PMID- 1312180 TI - [Cytomegaloviral interstitial pneumonia after autologous bone marrow transplantation in a case of acute lymphoblastic leukemia. Bone Marrow Transplantation Team]. AB - A 22-year-old man with T cell type acute lymphoblastic leukemia in first remission underwent autologous bone marrow transplantation (BMT). The preparative regimen included cytosine arabinoside, cyclophosphamide and fractionated total body irradiation. His harvested bone marrow cells were purged with 4 hydroperoxycyclophosphamide. His serological test was positive for cytomegalovirus (CMV) before the BMT. On day 53 after the BMT, he developed dry cough and his chest X-ray film showed bilateral basilar infiltration. Bronchoalveolar lavage was performed and cytology of the specimen revealed typical cytomegaloviral inclusion bodies. DNA analysis and viral culture of the specimen were also positive for CMV. The patient was started on ganciclovir and immunoglobulin with high dose methylprednisolone. His respiratory status deteriorated, however, and the patient expired because of respiratory failure. Autopsy revealed severe interstitial pneumonitis with suppression of CMV replication from the treatment. Interstitial pneumonitis due to CMV should be considered as a significant complication of autologous BMT. PMID- 1312181 TI - [Suppression of in vitro hemopoiesis by the monocytes in a patient with aplastic anemia associated with hepatitis]. AB - The cause of aplastic anemia associated with hepatitis (AAH) is as yet still unknown. There is a supposed relation to the immune mechanisms, however few reports have shown the effects of monocytes on the pathogenesis in the patients with AAH. We have reported a case of a 12-year-old boy with AAH related to cytomegaloviruses, and studied the hemopoietic progenitors. He showed pancytopenia and hypoplasia of the bone marrow on admission to our hospital. The culture studies showed that mononuclear cells (MNC) of the bone marrow produced few hemopoietic colonies in all cell lineages. However, the depletion of adherent cells from the MNC increased numbers of erythroid, neutrophil-macrophage and megakaryocyte colonies. Furthermore, the addition of adherent cells of the peripheral blood suppressed the colony formation in the aforementioned cell lineages by marrow MNC from which adherent cells, phagocytic cells and T-cells were abrogated. The results way suggest that monocytes play some soles in the pathogenesis of aplasia through inhibitor of hemopoiesis. PMID- 1312182 TI - [Detection of cytomegalovirus in urine specimens from renal transplant recipients using polymerase chain reaction]. AB - Human cytomegalovirus (CMV) in this study, a polymerase chain reaction (PCR) assay was developed to detect human cytomegalovirus (CMV) from urine specimens taken from renal transplant patients and one congenital CMV infection. Twenty eight urine specimens of 20 renal transplant patients were analyzed by the PCR. CMV infection was detected in 11 specimens (8 recipients). The incidence (40.0%) of PCR positive in the renal transplant patients was highest among the other conventional methods including fluorescent antibody study, anti-IgM EIA and complement fixation test. In two cases, CMV infection could be identified by PCR before antibody development. The PCR procedure is more sensitive and rapid than conventional methods for the diagnosis of CMV. Rapid diagnosis of CMV infection using PCR may be useful in clinical diagnosis and have therapeutic value. PMID- 1312183 TI - [Evaluation of proposed criteria of disk susceptibility testing for tosufloxacin and lomefloxacin in NCCLS guidelines and WHO standards]. AB - Disk diffusion zone diameter breakpoint criteria for Tosufloxacin and Lomefloxacin were tentatively established by correlating MICs with 1-, 5- and 10 micrograms of Tosufloxacin disk inhibitory zone diameters and with 10 micrograms of Lomefloxacin disk of those to 418 clinical isolates representing 32 species. We recommend 5 micrograms disks for Tosufloxacin with the following breakpoints: Susceptible (MIC, less than or equal to 0.5 microgram/ml), greater than or equal to 22 mm; intermediate, 17 to 21 mm; and resistant (MIC, greater than or equal to 2.0 micrograms/ml), less than or equal to 16 mm. We recommend 10 micrograms disks for Lomefloxacin with the following breakpoints: Susceptible (MIC, less than or equal to 2.0 micrograms/ml), greater than or equal to 21 mm; intermediate, 16 to 20 mm; and resistant (MIC, greater than or equal to 8.0 micrograms/ml), less than or equal to 15 mm. Using these criteria for Tosufloxacin and Lomefloxacin, the occurrence rate of major errors in judging susceptibility and resistance was 0.48%. PMID- 1312184 TI - Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff. AB - The treatment of patients with a solitary brain metastasis has been evolving, with most centers recommending resection in patients with good performance status. To evaluate the results of resection of brain metastases from non-small cell lung cancer, we reviewed our 16-year experience with 185 consecutive patients undergoing resection of brain metastases from 1974 to 1989, inclusive. There were 89 men and 96 women; ages ranged from 34 to 75 years (median 54). Sixty-five (35%) had synchronous and 120 (65%) metachronous brain metastases. Discounting the brain metastasis, 68 patients (37%) had stage I, 13 (7%) stage II, 62 (33%) stage IIIA, 30 (16%) stage IIIB, and 12 (6%) stage IV carcinoma. There was no significant difference in age, locoregional stage (TN), or histologic features in patients with synchronous versus metachronous lesions. The overall survival rates (n = 185) were as follows: 1 year, 55%; 2 years, 27%; 3 years, 18%; 5 years, 13%; and 10 years, 7% (median 14 months). There was no significant difference in survival between patients with synchronous and metachronous lesions. To evaluate the impact of locoregional stage and treatment of the primary site, we analyzed only those patients with synchronous brain metastases. Multivariate analysis demonstrated that locoregional stage had no significant effect on survival (p = 0.97), but complete resection of the primary disease significantly prolonged survival (p = 0.002). Therefore complete resection, and not stage, of the locoregional primary lesion is the primary determinant of survival in patients undergoing resection of brain metastases from non-small-cell lung cancer. PMID- 1312185 TI - Cardiopulmonary bypass with a low-molecular-weight heparin fraction (enoxaparin) in a patient with a history of heparin-associated thrombocytopenia. PMID- 1312186 TI - High production of catalase in hydrogen peroxide-resistant human leukemia HL-60 cell lines. AB - The catalase activities of HP50-2 and HP100-1 cells, which are H2O2-resistant cell lines derived from human leukemia HL-60 cells, were 3 and 18 times higher, respectively, than that of HL-60 cells. These catalase activities of the resistant cells were precipitated with anti-catalase serum. The glutathione peroxidase activity of HP50-2 cells was about twice that of HL-60 or HP100-1 cells. The superoxide dismutase activities of HP50-2 and HP100-1 cells were, respectively, about 4 and 2 times that of HL-60 cells. In addition, both the resistant cell lines were completely devoid of myeloperoxidase activity. Pulse labeling experiments showed that the syntheses of catalase in HP50-2 and HP100-1 cells were, respectively, 2 and 4 times that in HL-60 cells, and that, unlike the parent cells, neither line synthesized myeloperoxidase. Thus the alteration of catalase, glutathione peroxidase, and superoxide dismutase activity could be linked to the resistance of H2O2 of human leukemia cells. PMID- 1312187 TI - Mayo Clinic experience with allogeneic and syngeneic bone marrow transplantation, 1982 through 1990. AB - Between April 1982 and July 1990, 101 patients underwent allogeneic or syngeneic bone marrow transplantation at the Mayo Clinic. This patient population consisted of 30 with acute nonlymphocytic leukemia, 25 with acute lymphoblastic leukemia, 29 with chronic granulocytic leukemia, and 17 with other diseases (aplastic anemia in 7, myelodysplastic syndrome in 5, and lymphoma in 5). The results achieved in our patients who underwent transplantation in first complete remission of both acute nonlymphocytic leukemia and acute lymphoblastic leukemia compare favorably with previously reported results. Only 1 of 15 patients (7%) with acute nonlymphocytic leukemia and 2 of 8 patients (25%) with acute lymphoblastic leukemia who underwent transplantation in first complete remission had a relapse. Thus, we recommend early bone marrow transplantation during initial complete remission for patients with either of these disorders who have adverse prognostic factors. In contrast, of 12 patients with either acute nonlymphocytic leukemia or acute lymphoblastic leukemia who underwent transplantation during relapse, 11 died within 6 months. Therefore, such patients should be offered new experimental treatments. Our patients with chronic granulocytic leukemia fared better when they underwent transplantation early during the course of their disease rather than during the accelerated or blast phase. Prospective studies are needed to determine the best approach in these patients. PMID- 1312188 TI - Diagnostic bronchoalveolar lavage in immunosuppressed patients with new pulmonary infiltrates. PMID- 1312189 TI - [Human immunodeficiency virus infection and neurological changes]. PMID- 1312190 TI - Experimental applications of porous (coralline) hydroxylapatite in middle ear and mastoid reconstruction. AB - Hydroxylapatite is a ceramic implant material which has been extensively investigated in the orthopedic and oral surgical literature. A set of animal experiments was carried out to determine the feasibility of the use of porous (coralline) hydroxylapatite for middle ear and mastoid reconstruction. Coralline hydroxylapatite was placed in the mastoid bulla of dogs and was carved into struts which were placed into the middle ear and against the tympanic membrane. Coralline hydroxylapatite is a highly biocompatible material which showed abundant ingrowth when in contact with host bone. There was also good soft-tissue ingrowth and fibrous tissue fixation within the middle ear and against the tympanic membrane. Hydroxylapatite is generally accepted to be osteoconductive, but not osteogenic. However, one of the specimens described with chronic inflammatory mucosal changes, shows de novo new bone formation within the pores of the graft. While normally the bone formed in coralline hydroxylapatite is secondary (lamellar), in this specimen primary (woven) bone was found. Porous (coralline) hydroxylapatite appears to be an excellent otologic graft material. It biointegrates with the host, is osteoconductive, and under certain circumstances may be osteogenic. PMID- 1312191 TI - Comparison of pulsed and continuous wave light in photodynamic therapy of papillomas: an experimental study. AB - Papillomavirus infection of the upper aerodigestive tract is a serious and potentially life-threatening disease which can result in complete respiratory obstruction. Papillomas are the most common benign neoplasm of the larynx in children but have been shown to have an equal propensity to occur in adults. The hallmark of this disease is one of multiple recurrences despite adequate surgical removal, often resulting in a frustrating and prolonged clinical course. Multiple treatment modalities have been used throughout the years, unfortunately with limited success. Recent reports on the treatment of virally induced lesions with photodynamic therapy (PDT) using hematoporphyrin derivative (HPD) or its newly purified form dihematoporphyrin ether (DHE) as photosensitizing agents have appeared in the literature. The successful treatment of papillomas in both the animal model and humans holds great promise. The most commonly used activating light source has been the argon pumped-dye laser (ADL) which produces a continuous wave of coherent light at 630 nm. Although the ADL has proved efficacious in most studies, its cost, size, special cooling water requirements, and large electrical power requirements with limited power output have made it a less than desirable clinical tool. The gold vapor laser (GVL) has been recently proposed as a possible alternate light source for PDT. This laser appears to be more efficient and offers greater power output while requiring less electrical energy than the ADL. The GVL does not produce the same continuous wave light as the ADL but emits pulsed light with high peak power pulses. Some reports have shown a greater tumor response using the GVL at 628 nm, possibly because of greater tissue penetration from the high-peak power pulses. At this time, no studies have investigated the effects of pulsed light during PDT on virally induced papillomas. The present study was conducted to evaluate the efficacy of pulsed light from a GVL as compared to continuous wave light of the ADL in the treatment of papillomas with DHE phototherapy. Statistical analysis of the rate of tumor response, histological changes, and molecular analysis of viral DNA from the involved tissues were performed. Results have shown that the GVL did produce a greater initial rate of tumor response during the first 3 weeks after PDT but did not improve the overall cure rate. Histological and molecular analysis of the treated tissues demonstrated that similar results were obtained when either the ADL or GVL were used as activating light sources. PMID- 1312192 TI - The role of mu1 receptor in physical dependence on morphine using the mu receptor deficient CXBK mouse. AB - It is known that the CXBK inbred strain of mouse is deficient in mu1 opioid receptors, whereas the strain has a delta opioid receptor population that is less consistently altered. In the present study, we compared physical dependence on morphine between CXBK and C57BL/6 mice. Both strains of mice were treated with morphine-admixed food for 5 days. During the treatment, the two strains of mice showed no signs of toxicity. There was no significant difference in morphine intake during the treatment between CXBK and C57BL/6 mice. After the treatment, the withdrawal was precipitated by injecting naloxone (0.01-30 mg/kg, s.c.). CXBK mice showed weight loss, diarrhea and ptosis, but not jumping and body shakes after low dose of naloxone. Whereas, C57BL/6 mice showed weight loss, diarrhea, ptosis, body shakes and jumping. These results suggest that naloxone-precipitated weight loss, diarrhea and ptosis may be mediated by mu2 and/or delta opioid receptor, while naloxone-precipitated jumping and body shakes may be mediated by mu1 opioid receptors. PMID- 1312193 TI - Adrenal glands of mouse and rat do not synthesize androgens. AB - Human adrenal glands produce considerable amounts of the C-19 steroids dehydroepiandrosterone (DHEA) and androstenedione. To investigate the capability of rodent adrenals to produce these steroids, cell suspensions of mouse and rat adrenal glands were incubated in the absence and presence of adrenocorticotropic hormone (ACTH). Corticosterone levels in the incubation medium increased dramatically in the presence of ACTH, but no significant amounts of 17 hydroxyprogesterone or androstenedione could be detected. This indicates that the adrenals of rat and mouse lack the enzyme 17 alpha-hydroxylase. Absence of plasma cortisol in the presence of high levels of corticosterone confirmed these data. Plasma levels of androstenedione were significantly decreased in castrated male rats as compared to levels observed in intact males, showing the contribution of the testes to the plasma content of androstenedione. Very low levels of androstenedione were observed in female, male and castrated male mice. Plasma concentrations of DHEA were not detectable in intact and castrated male mice and rats. It is concluded that rat and mouse lack the enzyme necessary to synthesize adrenal C-19 steroids and that the adrenals in these animals, therefore, do not contribute to plasma levels of androstenedione and DHEA. PMID- 1312194 TI - The effect of immune mediators (cytokines) on the release of endothelium-derived relaxing factor (EDRF) and of prostacyclin by freshly harvested endothelial cells. AB - The effect of recombinant tumor necrosis factor and other cytokines stimulated by LPS (lipopolysaccharide), on the release of endothelial-derived relaxing factor and of prostacyclin was investigated using freshly harvested endothelial cells attached to plastic microcarrier beads. The results show that the cytokines failed to interfere with the release of EDRF and prostacyclin under the conditions of these experiments. PMID- 1312195 TI - An ESR-CT imaging of the head of a living rat receiving an administration of a nitroxide radical. AB - Three-dimensional ESR imaging of a living rat has been performed by an L-band ESR system, which is composed of an L-band ESR spectrometer, a field gradient coil, and a data processor. The imaging was carried out by Lauterbur's method. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL), was used as an imaging agent in saline solution at a concentration of 0.2 M and administered intraperitoneally to obtain a constant concentration in the head for about an hour. It took about 40 min to obtain one set of ESR-CT images. The cross sectional images were made, both as coronal and horizontal images. In the images of the rat head the nitroxide-rich region was clearly distinguished from the deficient region. The nitroxide-deficient areas corresponded well to the brain of the rat. PMID- 1312196 TI - Differential regulation of striatal preproenkephalin mRNA by D1 and D2 dopamine receptors. AB - The effect of administration of subtype selective dopamine (DA) agonists on the 6 hydroxydopamine (6-OHDA) lesion-induced increase of striatal preproenkephalin (PPE) mRNA was examined by dot-blot hybridization. Eight days following a unilateral 6-OHDA lesion of the substantia nigra pars compacta (SNc), PPE mRNA levels in the ipsilateral striatum were increased approximately two-fold. Administration of the D2 DA agonist, quinpirole, dose-dependently attenuated the 6-OHDA lesion-induced increase in striatal PPE mRNA. The effect of quinpirole was blocked by coadministration of the D2 DA antagonist eticlopride. In contrast, administration of the D1 DA agonist, SKF 38393, either dose-dependently augmented or had no effect on the 6-OHDA lesion-induced increase in striatal PPE mRNA. In the contralateral striatum, administration of quinpirole decreased PPE mRNA, while administration of SKF 38393 increased PPE mRNA compared to sham lesioned control levels. These data suggest the action of DA at D1 and D2 DA receptors differentially regulates striatal PPE mRNA levels and the apparent inhibition of ENK biosynthesis by DA is mediated via an interaction with D2 DA receptors. PMID- 1312197 TI - Differential regulation of muscarinic and nicotinic cholinergic receptors and their mRNAs in cultured sympathetic neurons. AB - Mechanisms regulating expression of neuronal muscarinic and nicotinic receptors were examined in cultures of neonatal rat sympathetic neurons. Two factors known to stimulate cholinergic transmitter development in sympathetic neurons were examined for their effects on cholinergic receptor expression. A membrane associated factor (MANS46) and a diffusible factor produced by cultured rat fibroblasts (RFCM) each decreased muscarinic receptor number. By contrast, neither treatment altered levels of nicotinic receptors. Levels of muscarinic (m2) receptor mRNA were decreased by MANS but not by RFCM, indicating that effects of the two treatments were mediated by different mechanisms. Neither MANS nor RFCM altered levels of nicotinic alpha 3 or beta 2 mRNAs, consistent with the lack of change in numbers of nicotinic receptors. These observations indicate that receptor phenotype in developing neurons is subject to regulation by multiple epigenetic factors. Further, the same signals which regulate transmitter development may also regulate receptor expression in sympathetic neurons. PMID- 1312198 TI - Ontogeny of D1 and DARPP-32 gene expression in the rat striatum: an in situ hybridization study. AB - D1 dopamine receptor (D1R) and DARPP-32 (a dopamine and adenosine 3',5' monophosphate regulated phosphoprotein), gene expression was studied in the rat striatum in adults and during ontogeny by in situ hybridization. D1R mRNA was first detected in the striatal primordium at day 17 of gestation. At day 18, D1R mRNA was found throughout the striatum. Before birth, the striatal neurons had neuroblastic aspect and were close together, giving homogeneous and compact labelling. After birth, the topography and aspect of the neurons containing D1R mRNA and DARPP-32 mRNA were similar. The two mRNAs were detectable in the caudate putamen, accumbens nucleus and olfactory tubercle. The microautoradiographic analysis demonstrated that D1R and DARPP-32 genes are massively expressed by the medium-sized striatal neurons. The proportion of medium-sized neurons containing the DARPP-32 mRNA was however higher than that of the neurons containing the D1R mRNA. Furthermore, an unexpected proportion of large-sized neurons express these genes. This proportion varies with development. Comparison between the appearance, topography and frequency of choline-acetyltransferase immunoreactive neurons and large-sized neurons containing D1R or DARPP-32 mRNA suggest that these large-sized neurons containing D1R and DARPP-32 mRNAs are cholinergic ones. PMID- 1312199 TI - Induction of transcription factors in somatosensory cortex after tactile stimulation. AB - Immediate early response genes have been shown to be inducible in the central nervous system after a variety of stimuli. Induction of these transcription factors in cerebral cortex by a physiological stimulus had not previously been demonstrated. In this study, tactile stimuli induced multiple transcription factors in the somatosensory cortex. Adult male rats were lightly anesthetized with urethane. Tactile stimuli was delivered by a paint brush gently stroking an animals whiskers on one side of its face for a 15 min period. Two h later, the animals were sacrificed. Cortex contralateral to the stimulation was compared with ipsilateral cortex using antibodies raised against immediate early response gene products NGFI-A, NGFI-B, and c-fos. The different transcription factors showed slightly different patterns of response to the tactile stimulus. However, the induction of immunohistochemical staining was most prominent in layer 4 with all antibodies under study. This increase in the number of cell bodies stained was less robust than that seen in the somatosensory cortex after a seizure, and showed more of a predominance in layer 4 cells. These data demonstrate that physiologic stimulation can induce immediate early response genes in cortical cells, and that multiple immediate early response genes react to a stimulus. PMID- 1312200 TI - Glucocorticoid-mediated down regulation of c-fos mRNA in C6 glioma cells: lack of correlation with proenkephalin mRNA. AB - We investigate the linkage between the transcriptional factor, c-fos, and expression of proenkephalin in rat C6 glioma cells. C6 cells contained abundant levels of c-fos mRNA. Treatment of cells with dexamethasone resulted in a 10-fold decline in c-fos transcripts and a small increase in proenkephalin mRNA. Combined exposure to dexamethasone and isoproterenol also induced a decrease in c-fos mRNA while proenkephalin mRNA increased 8-fold. Treatment of the C6 cells with phorbol 12-myristate 13-acetate caused a 13-fold increase in c-fos expression 0.5 h after administration and a decrease in proenkephalin mRNA. These data indicate that c fos and proenkephalin mRNA are not regulated in a sequential, parallel manner, that newly synthesized c-fos is not the determining factor controlling proenkephalin gene regulation, and that c-fos expression is under negative control by glucocorticoids. PMID- 1312201 TI - Differential regulation of chromogranin B/secretogranin I and secretogranin II by forskolin in PC12 cells. AB - The factors which regulate the expression of the granin family of secretory proteins have yet to be completely described. The present study investigated the effects of forskolin (FSK), an activator of adenylate cyclase, on the regulation of chromogranin B/secretogranin I (CgB) and secretogranin II (SgII) mRNA levels in rat PC12 cells. PC12 cells were treated with 10 microM FSK for time points up to 48 h and were harvested for cAMP determination, RNA isolation and Northern blot analysis, or fixed in 4% paraformaldehyde for immunocytochemistry. Cellular cAMP levels peaked after two h of FSK treatment and remained elevated for 48 h. Chromogranin B mRNA increased with FSK treatment, reaching a maximum of 7-fold above control after 24 h, while the level of SgII mRNA decreased to a level of 65 +/- 10% of control after 48 h. The effects of FSK on CgB mRNA appear to be mediated by cAMP, as 8-bromo-cAMP (500 microM) resulted in a 2.8-fold increase in CgB mRNA, and H-89 (30 microM), a selective inhibitor of cAMP-dependent protein kinase, reduced the FSK-mediated response. The level of CgB was also increased in FSK-treated cells, as evidenced by immunofluorescent analysis which showed a more intense staining in PC12 cells treated with FSK for 48 h than in untreated cells. The intensity of SgII staining was diminished by FSK treatment, most likely a result of a decreased rate of synthesis as well as an increase in the release of SgII. This study demonstrated that the mRNA and protein levels of CgB and SgII are differentially regulated by cAMP in PC12 cells. PMID- 1312202 TI - Characterization of the major 68 kDa heat shock protein in a rat transformed astroglial cell line. AB - The heat shock response in a transformed astrocyte line was compared with nontransformed astrocytes. The synthesis of HSP 68, the major inducible heat shock protein (HSP 68) was induced by a non-lethal 45 degrees C, 10 min heat shock. Although the incorporation of [35S]methionine into HSP 68 suggested that similar amounts of protein were being synthesized after heat shock, Western immunoblotting demonstrated striking differences in the HSP immunostaining between the two cell types. By one- and 'two-dimensional gel electrophoresis the major 68 kDa heat shock protein (HSP 68) was similar in both cell types. However, HSP 68 from heat shocked, transformed astrocytes did not immunostain with the monoclonal antibody, C-92, which is specific for the major inducible heat shock protein of HeLa cells. In contrast HSP 68 from heat shocked, nontransformed astrocytes immunostained quite well. A polyclonal antibody raised against the inducible 72 kDa heat shock protein of HeLa cells immunostained the HSP 68 from both astrocytes and transformed astrocytes. Analysis of the mRNA from the two cell types after heat shock revealed two bands of approximately 2.5 and 2.8 kb in astrocytes but only a single 2.5 kb band in the heat shocked transformed astroglia. These results suggest that structural differences in the HSP 68 may be present in the transformed astrocytes compared to the normal astrocytes. PMID- 1312203 TI - Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing. AB - The nature and distribution of preprotachykinin (PPT, i.e. substance P/neurokinin A-encoding) gene expression in human basal ganglia was determined. Northern blot analysis visualized a single band of approximately 1300 bases, confirming the postmortem stability of PPT mRNA. Gross anatomical analysis indicated that PPT gene expression was relatively evenly distributed throughout the human caudate and putamen, but absent in the globus pallidus and substantia nigra. Nuclease protection analysis of these tissues established that human PPT mRNA consisted of approximately 80-85% beta-PPT (exon 1-7 derived) mRNA and 15-20% gamma-PPT (minus exon 4), with no alpha-PPT (minus exon 6) mRNA detected; these data contrast with the proportions of PPT mRNAs seen in non-human species. The incompletely spliced PPT RNA species detected in basal ganglia accounted for approximately 8% of total human PPT RNA and suggested a fixed order of exon splicing. Since various PPT mRNAs encode different combinations of tachykinin peptides with distinct biological activities, the markedly different proportions of PPT mRNAs seen in human basal ganglia compared to non-human tissues may be of physiological significance. PMID- 1312205 TI - Differential dopaminergic regulation of proenkephalin and prodynorphin mRNAs in the basal ganglia of rats. AB - Proenkephalin and prodynorphin mRNA levels in the caudate-putamen and in the nucleus accumbens of rats were measured by in situ hybridization 2, 4 and 8 weeks following unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine (6-OHDA). After 2 weeks a 60% increase of the levels of proenkephalin mRNA in the ipsilateral caudate-putamen was observed which declined to 20% above control after 8 weeks. A smaller increase in the levels of proenkephalin mRNA of about 20% was observed in the nucleus accumbens after 2 weeks and no significant alteration could be observed 4 and 8 weeks after lesioning. The levels of prodynorphin mRNA in the ipsilateral caudate-putamen decreased 20% below control and returned to control levels 4 and 8 weeks post-lesion. In contrast, in the nucleus accumbens a persistent ipsilateral decrease of prodynorphin (20-30%) was found 2, 4 and 8 weeks post-lesion. These findings indicate, that lesions of the mesostriatal dopamine (DA) system differentially influences opioidergic gene expression in distinct areas of the caudate-putamen. The lesions cause an increase in proenkephalin mRNA levels which was higher in the caudate-putamen than in the nucleus accumbens and tend to be reversible. Conversely, the lesion caused a persistent decrease in the levels of prodynorphin mRNA in the nucleus accumbens and a small and transient decrease in the caudate-putamen. PMID- 1312204 TI - Long-term expression of the c-fos protein during the in vitro differentiation of cerebellar granule cells induced by potassium or NMDA. AB - Levels of the c-fos protein were assayed in mouse cerebellar granule cells during their in vitro development under different culture conditions. When grown in media favoring both their survival and differentiation, i.e. in the presence of 30 mM K+ or 12.5 mM K+ plus 100 microM N-methyl-D-aspartate (NMDA), the c-fos protein becomes detectable in the nucleus of granule cells on and after 6 days and persists to high levels until the culture begins to decline. The protein c fos appears therefore after the critical period described for the survival effect of K+ depolarization or NMDA receptor stimulation which corresponds to days 2-5 after plating. The c-fos protein remains however scarcely detectable or undetectable throughout the life-span of cells cultured under conditions providing poor survival and differentiation, i.e. in the presence of low K+ (5 or 12.5 mM) alone or when the effect of NMDA is blocked by the NMDA receptor antagonist MK-801. Interestingly, in cortical and striatal neurons, the survival and differentiation of which being not affected by depolarizing media, no c-fos protein is detected whatever the culture conditions tested at least during the first 18 days in vitro. This suggests that long-term expression of the c-fos gene might be related to some aspect of the late in vitro differentiation process of cerebellar granule cells. PMID- 1312206 TI - Quantitative in situ hybridization evidence for differential regulation of proenkephalin and dopamine D2 receptor mRNA levels in the rat striatum: effects of unilateral intrastriatal injections of 6-hydroxydopamine. AB - Nigrostriatal (NS) dopaminergic (DA) neurons are thought to exert an inhibitory influence on striatal enkephalinergic systems through their DA D2 receptors. In order to investigate the effects of partial lesions of the NS DA on striatal proenkephalin (PEK) and D2 receptor mRNAs, animals were allocated to High, Intermediate, and Low rotators on the basis of amphetamine-induced rotation observed after intrastriatal injections of 6-hydroxydopamine (6-OHDA). On the ipsilateral side of the lesions, there were significant increases in PEK mRNA in the total aspect of the caudate-putamen (CPu) of the High (+204%), the Intermediate (+125%), and of the Low (+67%) rotation groups in comparison to controls; these changes correlated positively with increases in rotation rate. Unexpectedly, there were also significant increases in striatal PEK mRNA on the contralateral side although these changes were much less prominent than those observed on the side of the lesions. Conversely, only the High rotation group showed significant increases (+112%) in D2 receptor mRNA which occurred only on the lesioned side. Interestingly, the low rotation group actually showed some non significant decreases (-25%) on the side of the lesions. These results indicate that partial lesions of the NS DA projections are sufficient to cause substantial increases in PEK mRNA but not in D2 receptor mRNA. These data also provide evidence that the two nigrostriatal DA projections and the systems which they modulate might be under interdependent sets of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312207 TI - Isolation of a calreticulin-like calcium binding protein from bovine brain. AB - Intracellular calcium levels are stringently regulated in all cells. The nature of this regulation is incompletely understood, but recent evidence indicates that the endoplasmic reticulum plays an important role in sequestering intracellular calcium. Using methods for isolating both calsequestrin and calreticulin, we have isolated a 58 kDa, high capacity calcium binding protein that exists in microsomes that shift their density in an oxalate-mediated density shift assay. This protein which we call CBP-58 bears similarities to the endoplasmic reticulum protein, calreticulin, in that it has a pI of 4.7 containing approximately 30% glutamate and aspartate, has a high capacity for calcium, and stains blue with the carbocyanine dye, 'Stains-all'. Peptide, amino acid, nucleotide and immunochemical analyses reveal further similarities between CBP-58 and calreticulin, but also some marked differences. Its tissue distribution suggests it is highly enriched in brain versus other tissues. We believe that CBP-58 is a calreticulin-like protein and that differences in the amino acid composition and sequences may reflect species diversity in calreticulin. PMID- 1312208 TI - Dopaminergic regulation of cholecystokinin mRNA content in rat striatum. AB - The nigrostriatal dopaminergic activity was pharmacologically changed to assess whether dopamine (DA) regulates cholecystokinin (CCK) mRNA steady state in rat striatum. Cocaine and benztropine, two dopaminergic agonists known to induce DA release and to block its re-uptake, produced a time dependent increase in CCK mRNA content in rat striatum. A significant increase in striatal CCK mRNA was observed 8 h after a single injection of cocaine (15 mg/kg, i.p.) or benztropine (15 mg/kg, i.p.) whereas a two-fold increase was observed after a daily treatment for one week with these two dopaminergic agonists. Cocaine and benztropine failed to change CCK mRNA content in the cerebral cortex. Haloperidol, a dopaminergic receptor blocker, injected at 1 mg/kg, i.p., daily for 7 days, decreased CCK mRNA content in striatum but not in the cerebral cortex. Moreover, haloperidol blocked the effect of cocaine and benztropine, suggesting that the stimulation of striatal dopaminergic receptors is necessary for the induction of CCK biosynthesis. The neurotoxin 6-hydroxydopamine injected into the medial forebrain bundle, elicited a 50% decrease in striatal CCK mRNA, supporting the hypothesis that DA tonically regulates CCK biosynthesis in postsynaptic neurons. To characterize the dopaminergic receptor subtype involved in this regulation, BHT 920, a specific D2 receptor agonist and SKF 38393, a specific D1 receptor agonist were used. While one week treatment with BHT 920 (1 mg/kg, i.p.) increases striatal CCK mRNA content, SKF 38393 (3 mg/kg, i.p.) failed to change this parameter. These data suggest that the increase of striatal CCK mRNA is mediated by the activation of the D2 receptor subtype. PMID- 1312209 TI - In situ hybridization of calcium/calmodulin dependent protein kinase II and tau mRNAs; species differences and relative preservation in Alzheimer's disease. AB - Abnormal phosphorylation of the microtubule associated protein tau component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) may result from alterations in protein kinase expression. Calcium/calmodulin dependent protein kinase II (CaM kinase II) has been shown to phosphorylate tau in vitro in such a way to decrease its electrophoretic mobility. A68, apparently a modified form of tau in AD brain, also shows abnormal phosphorylation and slower mobility than tau. To further examine the role of CaM kinase II in AD, in situ hybridization studies were performed on tissues from rat, monkey and human to examine and compare the patterns of CaM kinase II mRNA expression in different brain regions. The most notable differences among the three species were observed in dendrites in layer I of isocortex, in the molecular layer of the dentate gyrus and stratum radiatum and stratum lacunosum-moleculare in hippocampus, where hybridization was detected in rat, but not in monkey or human brain. In addition, comparisons between tau and CaM kinase II mRNA expression were made in tissue from normal aged adults and AD patients, especially in areas prone to NFT formation. CaM kinase II and tau mRNAs were co-expressed in many neuronal populations, both those which are prone to NFT formation as well as those which are rarely affected by AD changes. No major differences in the relative abundance of either CaM kinase II or tau mRNA within particular neuronal populations was noted between normal aged and AD brain. Diminished hybridization was associated with serve neuronal pathology and cell loss. PMID- 1312210 TI - Effects of gene transfer into cultured CNS neurons with a replication-defective herpes simplex virus type 1 vector. AB - Vectors derived from herpes simplex virus type 1 (HSV-1) may provide useful tools for gene transfer to cells of the mammalian nervous system. We have studied the infection of cultured CNS neurons using a vector derived from an HSV-1 mutant deleted for the major HSV-1 transcriptional regulatory protein-encoding gene, IE 3. This vector, denoted Cgal delta 3, contains the E. coli lacZ gene driven by the strong promotor of the human cytomegalovirus major immediate-early gene inserted into a non-coding portion of the mutant viral genome. We studied the efficiency of Cgal delta 3 infection of rat CNS neurons at various times after cell preparation from embryonic rats, the effect of vector infection on the glia subpopulation of the neuronal cultures, and the stability of lacZ expression in infected neurons cultured under conditions optimized for neuronal differentiation and survival using an astrocyte feeder layer. Under these conditions, an HSV derived vector is a highly efficient vehicle in vitro for short-term gene transfer to cells of the CNS. Despite the fact that this vector cannot undergo a lytic cycle, it was toxic to cultured CNS neurons and glia. Even with the use of an astrocyte feeder layer to support infected neurons, we have detected only transient expression of the lacZ gene, due either to loss of the infected cells and/or to shut off of transgene expression. Further improvements will be needed in the design of HSV vectors to allow long-term gene transfer to cultured neurons. PMID- 1312212 TI - Purification and initial characterization of AhrC: the regulator of arginine metabolism genes in Bacillus subtilis. AB - The arginine-dependent repressor-activator from Bacillus subtilis, AhrC, has been overexpressed in Escherichia coli and purified to homogeneity. AhrC, expressed in E. coli, is able to repress a Bacillus promoter (argCp), which lies upstream of the argC gene. The purified protein is a hexamer with a subunit molecular mass of 16.7 kDa. Its ability to recognize DNA has been examined in vitro using argCp in both DNase I and hydroxyl radical protection assays. AhrC binds at two distinct sites within the argCp fragment. One site, argCo1, with the highest affinity for protein, is located within the 5' promoter sequences, whilst the other, argCo2, is within the coding region of argC. The data are consistent with the binding of a single hexamer of AhrC to argCo1 via four of its subunits, possibly allowing the remaining two subunits to bind at argCo2 in vivo forming a repression loop similar to those observed for the E. coli Lac repressor. PMID- 1312213 TI - Cervical cancer--what role for human papillomavirus? AB - OBJECTIVE: To review the role of human papillomavirus (HPV) as a causative agent of cancer of the cervix. DATA SOURCES, data synthesis, study selection: Medical journals, recently published text books related to cancer of the cervix and HPV and Papillomavirus Reports were examined to review the pathology of cervical cancer and its precursor lesions, its epidemiology in Australia and overseas, methods of detection of HPV (in particular molecular biology techniques used to diagnose HPV) and evidence linking HPV with genital neoplasia. CONCLUSION: While there is compelling evidence strongly linking certain HPV types with genital cancer, a causative role is yet to be proven and the aetiology is most likely multifactorial. Detection and typing of high risk genotypes of HPV in the genital tract as a diagnostic exercise to identify those women most at risk of developing genital neoplasia is not currently recommended. PMID- 1312211 TI - Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. AB - We studied 71 patients with "paraneoplastic" encephalomyelitis, sensory neuronopathy, or both associated with the presence of the anti-Hu antibody in their serum. Most (78%) had small-cell lung cancer. In 9 patients no tumor was detected. Fifty-two patients (73%) had signs and symptoms of multifocal involvement of the nervous system; in 28 (39%), 2 areas, and in 24 (34%), 3 or more areas were clinically affected. Sensory neuronopathy was present in 52 patients (74%), but in only 44 (62%) did it dominate the course of the disease. Other predominant findings were: motor neuron dysfunction (14 patients, 20%), limbic encephalopathy (14, 20%), cerebellar symptoms (11, 15%), brainstem encephalopathy (10, 14%), and autonomic nervous system dysfunction (7, 10%). The presence of the anti-Hu antibody prompted a search for the tumor in 60% of the patients; the tumor when found was usually small and remained localized until death, or was demonstrated only at autopsy. Treatment using steroids and plasmapheresis, immunosuppressants, or both, did not improve the paraneoplastic symptoms. Autonomic and respiratory failure, either of central origin or secondary to neuromuscular weakness, were the principal causes of death. Patients with rapidly developing sensory neuropathy or symptoms of encephalomyelitis should be studied for the presence of the anti-Hu antibody; if the antibody is found, the possibility of small-cell lung cancer should be investigated. If a tumor is not found in the initial search, one may become evident in several months. PMID- 1312214 TI - Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum. AB - Endothelin receptors (ETRs) display subtype heterogeneity and are widely distributed throughout the tissues of the periphery and central nervous system. In order to gain further insight into the potential molecular differences of ETRs, we initiated molecular cloning of ETR genes by screening for the appearance of 125I-ET-1 binding activity in COS cells transfected with pools of a porcine cerebellum cDNA expression library. Two independent clones (pPCETR 1.1 and pPCETR 5.6) were identified and isolated by repeated rounds of pool enrichment and COS cell expression. DNA sequence analysis of pPCET 1.1 and pPCET 5.6 indicated that both clones have the same nucleotide sequence; the deduced amino acid sequence indicated that the porcine cerebellum ETR is 443 residues in length and consists of seven potential transmembrane domains, with homology to members of the GTP binding protein-coupled receptor superfamily. Northern analysis indicated a single mRNA species of about 5 kilobases, which is expressed significantly in cerebellum, lung, kidney, and pituitary. Expression of functional receptor was demonstrated by endothelin-1 (ET-1)-mediated Ca2+ mobilization in COS cells transfected with pPCETR 1.1 (COS/ETR 1.1) and ET-1-mediated electrophysiological responses in Xenopus oocytes injected with RNA derived from pPCETR 1.1. Quantitative comparison of saturation binding of 125I-ET-1 to either porcine cerebellum or COS/ETR 1.1 membranes indicated an identical apparent dissociation constant. The relative efficacy of ET-related peptides to compete for binding of 125I-ET-1 to receptor from porcine cerebellum and COS/ETR 1.1 indicated that both preparations encode a nonselective or ETBR subtype. Chemical cross-linking of 125I-ET-1 to receptor derived from cerebellum or COS/ETR 1 revealed two bands, with apparent molecular masses of 47 and 35 kDa. These data demonstrate that the pPCETR 1.1 encodes the major ETR subtype in the porcine cerebellum. PMID- 1312215 TI - Maitotoxin effects are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry. AB - The dinoflagellate toxin maitotoxin (MTX) elicited a sustained increase of [Ca2+]i in C6 glioma cells. This response was inhibited by SK&F 96365, a blocker of receptor-mediated calcium entry. In C6 cells, endothelin-1 elicited a rapid but transient increase in [Ca2+]i, followed by a smaller sustained increase. SK&F 96365 inhibited the sustained increase in [Ca2+]i. In both C6 glioma cells and RIN insulinoma cells, MTX elicited a marked influx of 45Ca2+. SK&F 96365 inhibited MTX-induced 45Ca2+ influx by 95% at 30 microM. The L-type calcium channel blocker nifedipine, even at 10 microM, inhibited MTX-induced calcium uptake by only 20% in RIN cells and by only 10% in C6 cells. MTX elicited calcium dependent phosphoinositide breakdown in both C6 and RIN cells. In both cell lines, the MTX-induced phosphoinositide breakdown was inhibited by 90% by SK&F 96365 at 30 microM. Endothelin-1 and carbamylcholine elicited phosphoinositide breakdown in C6 cells and RIN cells, respectively. The stimulations were unaffected by the presence of SK&F 96365 up to 100 microM. In RIN insulinoma cells, MTX elicited calcium-dependent release of insulin. SK&F 96365 at 30 microM inhibited MTX-induced insulin release by 75%, whereas nifedipine, even at 30 microM, inhibited release by only 10%. The blockade of MTX-induced responses by SK&F 96365 indicates that MTX increases intracellular calcium by interacting directly with a calcium-entry system that is similar, in its sensitivity to SK&F 96365, to the calcium-entry system activated by receptors that elicit phosphoinositide breakdown. Activation of phospholipase C and hormone release by MTX also are blocked by SK&F 96365 and, thus, may be secondary to the activation of such a calcium-entry system. PMID- 1312216 TI - Drug efficacy at guanine nucleotide-binding regulatory protein-linked receptors: thermodynamic interpretation of negative antagonism and of receptor activity in the absence of ligand. AB - The mutual effects that a hormonal ligand (H) and a guanine nucleotide regulatory protein (G protein) exert on each other when simultaneously occupying distinct sites of the receptor molecule (R) can be viewed as the molecular mechanism of drug efficacy. These effects are predictable on the basis of a model assuming that the ternary complex between the three partners (HRG) reaches equilibrium in the membrane [J. Biol. Chem. 255:7108-7117 (1980)]. Ligands can be classified as agonists, neutral antagonists, or negative antagonists, depending on whether they enhance, leave unchanged, or reduce, respectively, the spontaneous tendency of R to interact with G. Using this model and the assumption that the G protein response observed in membranes reflects the sum of ligand-independent (RG) and ligand-dependent (HRG) receptor-G protein complexes, we can explain virtually all the phenomenology reported earlier for opioid receptor-mediated stimulation of GTPase, i.e., 1) existence of ligands with both "positive" and "negative" intrinsic activity (the latter termed negative antagonists), 2) equipotency of neutral antagonists for the competitive blockade of the responses elicited both by agonists and by negative antagonists, and 3) apparent heterogeneity of binding sites for the binding isotherms of negative antagonists. The ternary complex model can also explain the differential effects of sodium on ligand binding and ligand-dependent GTPase activity, if we assume that this ion reduces the stability constant between receptor and G protein in membranes. Computer simulations predict that a negative antagonist exhibits a discrepancy between "biological" Ki (obtained by Schild plots) and true dissociation constant for the receptor, which increases as the fraction of "precoupled" receptors in the membrane increases. The demonstration of negative antagonism is definitive evidence for the existence of receptor coupling (hence activity) in the absence of ligand. Using this experimental paradigm, we show here that spontaneous receptor activity occurs in isolated membranes but not in intact NG108-15 cells. PMID- 1312217 TI - Competitive regulation of phospholipase C responses by cAMP and calcium. AB - DDT1-MF2 smooth muscle cells demonstrated a robust phospholipase C response to norepinephrine, as detected by inositol phosphate accumulation. A selective A1 adenosine receptor agonist, cyclopentyladenosine, caused only a minor stimulation of phospholipase C, which was eliminated in the absence of added extracellular calcium. The simultaneous addition of norepinephrine and cyclopentyladenosine resulted in a synergistic increase in phosphoinositide hydrolysis either in the absence or in the presence of external calcium. In the presence of external calcium and a calcium ionophore, and adenosine agonist caused a significant stimulation of phosphoinositide hydrolysis without the addition of norepinephrine. Influx of extracellular calcium through voltage-sensitive calcium channels did not appear to be required to observe an effect of cyclopentyladenosine, because neither calcium channel antagonists (nifedipine, verapamil, and LaCl3) nor a chelator of extracellular calcium (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) were able to alter the degree of potentiation of norepinephrine-stimulated phosphoinositide hydrolysis due to the adenosine agonist. On the other hand, buffering of intracellular calcium concentration with the membrane-permeant calcium chelator quin2 blocked the potentiation. This blockade of potentiation by quin2 was reversed by the addition of extracellular calcium. Agents that stimulated cAMP production or membrane-permeable analogues of cAMP also blocked the action of the adenosine agonist to potentiate norepinephrine-stimulated phosphoinositide hydrolysis. This effect of cAMP was less pronounced in the presence of elevated extracellular calcium and was abolished in the presence of a calcium ionophore. When norepinephrine-stimulated calcium transients were quantitated using fura-2 fluorescence, a reduction in the amplitude of the calcium response was observed in the presence of forskolin. Conversely, both the amplitude and the duration of the calcium response were enhanced by the addition of the adenosine agonist. The results of these studies suggest that the mechanism by which adenosine receptors enhance the stimulation of phosphoinositide hydrolysis is dependent upon a rise in intracellular Ca2+ concentration resulting from the simultaneous activation of alpha 1-adrenergic receptors. The results further suggest that cAMP inhibits this mechanism by decreasing the norepinephrine-stimulated rise in intracellular Ca2+ concentration. PMID- 1312218 TI - Cyclic AMP differentiates two separate but interacting pathways of phosphoinositide hydrolysis in the DDT1-MF2 smooth muscle cell line. AB - The activation of adenosine A1 receptors in DDT1-MF2 smooth muscle cells resulted in both the inhibition of agonist-stimulated cAMP accumulation and the potentiation of norepinephrine-stimulated phosphoinositide hydrolysis. Pharmacological analysis indicated the involvement of an A1 adenosine receptor subtype in both of these responses. In the absence of norepinephrine, the activation of the adenosine receptor did not directly stimulate phosphoinositide hydrolysis. The adenosine receptor-mediated augmentation of norepinephrine stimulated phosphoinositide hydrolysis was pertussis toxin sensitive and was selectively antagonized by agents that mimicked cAMP (8-bromo-cAMP) or raised cellular cAMP levels (forskolin). This initially suggested that cAMP might partially regulate the magnitude of the phospholipase C response to norepinephrine and that adenosine agonists might enhance the phospholipase C response by reducing cAMP levels. However, neither the reduction of cellular cAMP levels by other agents nor the inhibition of cAMP-dependent protein kinase was sufficient to replicate the action of adenosine receptor activation on phosphoinositide hydrolysis. Thus, in the presence of norepinephrine, adenosine receptor agonists appear to stimulate phosphoinositide hydrolysis via a pathway that is separate from, but dependent upon, that of norepinephrine. This second pathway can be distinguished from that which is stimulated by norepinephrine on the basis of its sensitivity to inhibition by both cAMP and pertussis toxin. PMID- 1312219 TI - HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA binding ability of myogenic regulatory factors. AB - Proteins containing the basic-helix-loop-helix (B-HLH) domain have been shown to be important in regulating cellular differentiation. We have isolated a cDNA for a human B-HLH factor, denoted HEB, that shares nearly complete identity in the B HLH domain with the immunoglobulin enhancer binding proteins encoded by the E2A and ITF2 genes (E proteins). Functional characterization of the protein expressed from this cDNA indicates that HEB is a third member of the E-protein class of B HLH factors. HEB mRNA was found to be expressed in several tissues and cell types, including skeletal muscle, thymus, and a B-cell line. HEB, ITF2, and the E12 product of the E2A gene all bound to a similar spectrum of E-box sequences as homo-oligomers. All three factors also formed hetero-oligomers with myogenin, and the DNA-binding specificity and binding off-rates (dissociation rates) were modulated after hetero-oligomerization. Both homo- and hetero-oligomers of these proteins were able to distinguish between very closely related E-box sequences. In addition, HEB was shown to form hetero-oligomers with the E12 and ITF2 proteins. Finally, HEB was able to activate gene expression. These data demonstrate that HEB shares characteristics with other E proteins and show that HEB can interact with members of both the myogenic regulatory class and the E protein class of B-HLH factors. HEB is therefore likely to play an important role in regulating lineage-specific gene expression. PMID- 1312220 TI - Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. AB - The effect of mammary gland-specific expression of the polyomavirus middle T antigen was examined by establishing lines of transgenic mice that carry the middle T oncogene under the transcriptional control of the mouse mammary tumor virus promoter/enhancer. By contrast to most transgenic strains carrying activated oncogenes, expression of polyomavirus middle T antigen resulted in the widespread transformation of the mammary epithelium and the rapid production of multifocal mammary adenocarcinomas. Interestingly, the majority of the tumor bearing transgenic mice developed secondary metastatic tumors in the lung. Taken together, these results suggest that middle T antigen acts as a potent oncogene in the mammary epithelium and that cells that express it possess an enhanced metastatic potential. PMID- 1312221 TI - Mapping neuroinvasiveness of the herpes simplex virus type 1 encephalitis inducing strain 2762 by the use of monoclonal antibodies. AB - Monoclonal antibodies (MAbs) directed against herpes simplex virus (HSV)-coded glycoproteins gB, gC, gD and gE were employed in a an in vitro model of neuroinvasiveness using sensory neurons from rat dorsal root ganglion (DRG) cells. The neurons were cultured in at two-chamber system allowing infection via the neuritic extensions exclusively. The effects of 30 MAbs on viral replication of the encephalitis-derived HSV-1 strain 2762 and its less neuroinvasive variant 2762p11 were assayed in this model. One MAb reactive with gD gave a nine-fold reduction of the virus yields of both strains. One MAb directed against gB gave an enhanced virus yield of strain 2762, but not of the 2762p11 variant. Another gB-reactive MAb decreased the virus yield of strain 2762p11, but not of 2762 after neuritic infection. The findings indicate that an alteration of gB has occurred during the passage of the strain 2762. Mutants of the same strain were derived by infecting hybridomas producing MAb reactive with gB, gC, gD and gE, respectively. The gB hybridoma mutant showed a significantly lower neuroinvasiveness in the DRG model, and was non-virulent after snout infection of mice. We suggest that the structure of gB of the strain 2762 is of importance for the neuroinvasiveness of this strain. PMID- 1312222 TI - Detection of human cytomegalovirus in peripheral mononuclear cells and urine samples using PCR. AB - Samples of peripheral blood lymphocytes from 105 different blood donors were investigated for the presence of human cytomegalovirus (HCMV) DNA using the polymerase chain reaction (PCR) with primers specific for the Pst I w fragment (IE region). Viral DNA sequences were detected in 53 samples, a fifth of which had been previously serotyped as HCMV negative. In the latter cases, Western blot analysis re-determined two out of three individuals that were resampled as seropositive. PCR could therefore be used to extend existing methods employed for the identification of HCMV infected blood samples prior to transfusion to individuals in high risk groups. In addition, the value of PCR as a diagnostic test was evaluated in a small pilot study by comparing the results obtained with urine samples from babies suffering congenital infection and from other high risk patients, with data obtained by isolation of infectious virus or through the detection of immediate early antigens in infected cultures. Data from this study indicated that PCR is at least as sensitive as the other methods used in HCMV diagnosis. PMID- 1312223 TI - Expression of type IV collagenase correlates with the invasion of human lymphoblastoid cell lines and pathogenesis in SCID mice. AB - An in vitro model, called the Membrane Invasion Culture System (MICS), was used to study the invasive potential of an Epstein-Barr virus (EBV) positive lymphoblastoid cell line (LCL), an EBV-negative Burkitt lymphoma (BL) cell line of American origin and an EBV-positive BL of African origin. MICS measured the ability of these cell lines to invade reconstituted basement membrane-coated filters, which correlated with their tumorigenic and metastatic capabilities in a SCID mouse model. Furthermore, the significantly greater invasive behaviour of the EBV-positive LCL was directly correlated with the cells' ability to express and secrete human type IV collagenase (72 kDa), an important metalloproteinase responsible for the degradation of collagen IV in basement membranes. The data suggest that MICS and the SCID mouse are useful tests of tumorigenicity in lymphoid cells, with measurable effects in both systems related to human type IV collagenase activity. Both models allow further exploration of malignant phenotypes associated with EBV transformation of lymphoid tissues. PMID- 1312224 TI - DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. AB - BACKGROUND: Ependymomas and papillomas of the choroid plexus occur in early childhood. The ubiquitous human polyomaviruses, BK virus and JC virus, have been associated with the induction of these neoplasms in animal models. A related monkey polyomavirus, simian virus 40 (SV40), is highly tumorigenic in rodents and also induces choroid plexus papillomas. METHODS: We tested the possibility that polyomaviruses were associated with these tumors in humans. Tumors from 31 children--20 with choroid plexus neoplasms and 11 with ependymomas--were evaluated for the presence of polyomavirus T-antigen gene sequences by means of amplification with the polymerase chain reaction. RESULTS: Ten of the 20 choroid plexus tumors and 10 of the 11 ependymomas contained amplification products that preferentially hybridized to probes specific for SV40 viral DNA rather than BK or JC viral DNA. In two specimens, DNA sequencing demonstrated that the amplified sequence was identical to the sequence of that region of the SV40 gene. In three other specimens, amplification with SV40-specific primers revealed a 574-bp segment of the SV40 viral gene. In 7 of 11 tumors examined by immunohistochemical staining, viral T antigen was expressed in the nuclei of the neoplastic cells. CONCLUSIONS: Half of the choroid plexus tumors and most of the ependymomas that we studied contained and expressed a segment of T-antigen gene related to SV40. These results suggest that SV40 or a closely related virus may have an etiologic role in the development of these neoplasms during childhood, as in animal models. PMID- 1312225 TI - Hormonal stimulation of adenylyl cyclase through Gi-protein beta gamma subunits. AB - Agonist-bound receptors activate heterotrimeric (alpha beta gamma) G proteins by catalysing replacement by GTP of GDP bound to the alpha subunit, resulting in dissociation of alpha-GTP from the beta gamma subunits. In most cases, alpha-GTP carries the signal to effectors, as in hormonal stimulation and inhibition of adenylyl cyclase by alpha s and alpha i respectively. By contrast, genetic evidence in yeast and studies in mammalian cells suggest that beta gamma subunits of G proteins may also regulate effector pathways. Indeed, of the four recombinant mammalian adenylyl cyclases available for study, two, adenylyl cyclases II and IV, are stimulated by beta gamma. This effect of beta gamma requires costimulation by alpha s-GTP. This conditional pattern of effector responsiveness led to the prediction that receptors coupled to many G proteins will mediate elevation of cellular cyclic AMP, provided that Gs is also active. We now confirm this prediction. Coexpression of mutationally active alpha s with adenylyl cyclase II converted agonists that act through 'inhibitory' receptors (coupled to Gi) into stimulators of cAMP synthesis. Experiments using pertussis toxin and a putative scavenger of beta gamma, the alpha subunit of transducin, suggest that beta gamma subunits of the Gi proteins mediated this stimulation. These findings assign a new signalling function to beta gamma subunits of Gi proteins, the conditional stimulation of cAMP synthesis by adenylyl cyclase II. PMID- 1312226 TI - Mutation of protein kinase A causes heterochronic development of Dictyostelium. AB - In heterochronic mutants the relative timing of developmental events is altered compared with the wild type. This generally results in a disordered embryo, though heterochronic mutations may also be an important source of evolutionary variation. In the rapidly developing (rde) mutants of Dictyostelium, stalk and spore cells differentiate before morphogenesis is complete. We have traced the lesion in one class of these mutants to the regulatory subunit of cyclic AMP dependent protein kinase (pk-A). Inactivation of this protein results in the unrestrained activity of the catalytic subunit, so prematurely triggering terminal cell differentiation. PMID- 1312227 TI - [For which infections should a multi-organ donor be serologically tested?]. PMID- 1312228 TI - [Support following pregnancy termination for genetic indications: experiences of involved women and their partners]. AB - By means of semistructured interviews with 40 women and their partners data were collected concerning on the one hand the care and support and on the other the grieving after termination of pregnancy performed because the child appeared to be genetically affected. Crucial in the grieving process is having to choose personally for or against termination of the pregnancy. This grieving process can be complicated by factors such as uncertainty concerning either the evidence of the disease or its prognosis, high recurrence risk, negative self-esteem, feelings of failure and pre-existent relational or personal problems. Clear and complete counselling, combined with structural support during the hospital stay, proves to be the basis of adequate care. Follow-up interviews after the hospital stay play a supporting part, both for the hospital workers and for the couple involved. PMID- 1312229 TI - The pathogenesis of cerebral gliomatous cysts. AB - In this study, the authors have examined the mechanism of the formation of tumor cysts. Cyst fluid samples were obtained during surgery and by percutaneous aspiration from 22 patients with cystic cerebral gliomas. The concentration of protein was measured in the cyst fluid and blood plasma. Analysis of brain tumor cyst fluids revealed that plasma proteins constituted a major fraction (92%) of cyst fluid proteins; moreover, the protein fractions occurred in concentrations (relative to the plasma concentrations) that were around 50-fold of those in cerebrospinal fluid. This strongly indicates blood-brain barrier disruption. Evidence from computed tomographic and magnetic resonance imaging scans as well as from electron microscopy of tumor cyst walls suggests the transition of spongy edematous tissue in or around tumors into the contents of associated cysts. Pathophysiologically, blood-brain barrier breakdown is inherent to the occurrence of vasogenic brain edema. It is therefore plausible that the development of cysts is related to peritumoral vasogenic edema. PMID- 1312230 TI - Combined intra-arterial and systemic chemotherapy for recurrent malignant brain tumors. AB - Seventy-nine patients harboring recurrent brain tumors received four cycles of infraophthalmic carotid injections of 160 mg of carmustine. Two milligrams of intravenous vincristine and 50 mg of oral procarbazine was also administered three times daily for 1 week in conjunction with each BCNU treatment. The response rate was 60% with a median survival for patients with astrocytomas, anaplastic astrocytomas, and glioblastomas of 32, 20, and 6.5 months, respectively. The median survival of the responding patients was 20 months, and the survival at 30 months was 45%. The survival in patients not responding to treatment was 5 months, reflecting the natural history of the tumor. There have been no deaths related to the treatment procedure. No incidents of severe or permanent eye complications or leukoencephalopathy were observed. Based on multivariate survival analysis, only patients with a good performance status who are not steroid dependent are candidates for this treatment. PMID- 1312231 TI - Receptor binding sites for cholecystokinin, galanin, somatostatin, substance P and vasoactive intestinal polypeptide in sympathetic ganglia. AB - Sympathetic ganglia are innervated by neuropeptide-containing fibers originating from pre- and postganglionic sympathetic neurons, dorsal root ganglion neurons, and in some cases, myenteric neurons. In the present report receptor autoradiography was used to determine whether sympathetic ganglia express receptor binding sites for several of these neuropeptides including bombesin, calcitonin gene-related peptide-alpha, cholecystokinin, galanin, neurokinin A, somatostatin, substance P, and vasoactive intestinal polypeptide. The sympathetic ganglia examined included the rat and rabbit superior cervical ganglia and the rabbit superior mesenteric ganglion. High levels of receptor binding sites for cholecystokinin, galanin, somatostatin, substance P, and vasoactive intestinal polypeptide were observed in all sympathetic ganglia examined, although only discrete neuronal populations within each ganglion appeared to express receptor binding sites for any particular neuropeptide. These data suggest that discrete populations of postganglionic sympathetic neurons may be regulated by neuropeptides released from pre- and postganglionic sympathetic neurons, dorsal root ganglion neurons, and myenteric neurons. PMID- 1312232 TI - [Lymphocytic infiltration in cerebral gliomas]. AB - The authors analyse the incidence, extent and prognostic significance of lymphocytic infiltration in 80 cases of operated cerebral gliomas (61 high- and 19 low-grade gliomas). The results obtained are discussed in relation to the data previously reported by the literature. PMID- 1312233 TI - [Evaluation of the safety and efficacy of the lisinopril + hydrochlorothiazide and captopril + hydrochlorothiazide combinations in the treatment of essential arterial hypertension]. AB - The aim of this study was to assess the efficacy and tolerability of the combinations of lisinopril (LIS) 20 mg + hydrochlorothiazide (HCTZ) 12.5 mg and captopril (CAP) 50 mg + HCTZ 25 mg in moderately hypertensive patients not adequately controlled by LIS or CAP alone. The study was multicentre (11 centres), open, random and carried out in parallel groups. After two weeks' placebo run in patients were randomly assigned to LIS 10-20 mg/o.d. or CAP 25-50 mg/b.i.d. treatment for 6 weeks. After this, patients with supine diastolic blood pressure (SDBP) greater than 90 mmHg were treated with the combinations LIS 20 mg + HCTZ 12.5 mg/o.d. or CAP 50 mg + HCTZ 25 mg/o.d. for 4 weeks; this dose was doubled if DBP was found to be greater than 90 mmHg after 2 weeks' combined therapy. A total of 175 patients were enrolled (92 females and 83 males) of which 153 completed the study. The LIS + HCTZ association caused a significant reduction of DBP in comparison to the other combined treatment (88.1 +/- 0.7 vs 90.3 +/- 0.7; p = 0.026). The statistical analysis of mean SBP values showed no significant difference between the two groups (144.0 +/- 1.3 vs 146.8 +/- 1.3; p = 0.15). At the end of the study 79.5% of patients treated with LIS + HCTZ presented normal results (DBP less than or equal to 90 mmHg), whereas the percentage of similar results in the comparison group was 72%. The percentage of "responder" patients to therapy (DBP reduced by 10 mmHg or more in relation to basal values) was 96.3% in the LIS + HCTZ group and 86.7% in the CAP + HCTZ group. In the CAP + HCTZ group 0.6% of patients reported adverse reactions, while only 0.3% were observed in the LIS + HCTZ group. PMID- 1312234 TI - Effect of ibuprofen on the in vitro and in vivo reactivation of latent HSV-1. AB - Prostaglandins have been suggested to play an important role in the reactivation of latent herpes simplex virus. To further understand the role of prostaglandins in the reactivation process, we investigated the effects of ibuprofen, a nonsteroidal anti-inflammatory drug with prostaglandin synthesis inhibitory activity, on the in vitro and in vivo reactivation of latent type 1 herpes simplex virus in mouse ganglia and rabbits, respectively. Ibuprofen, at a concentration of 50 or 100 microM, did not alter the titer of reactivated virus from explanted ganglia with latent virus, but, at a concentration of 200 or 500 microM, it significantly reduced the reactivated viral titer from the ganglia. Ibuprofen also directly inhibited the replication of herpes simplex virus in trigeminal ganglia and Vero cell monolayers, which indicates that the drug reduced the recovery of reactivated viral titers from explanted ganglia with latent virus by acting on the replication process rather than on the reactivation mechanism in vitro. The systemic administration of ibuprofen failed to demonstrate any significant effect on the ocular shedding of virus after attempted reactivation by 6-hydroxydopamine iontophoresis in rabbits with latent herpes simplex virus infection. This failure in vivo could be due to the short half-life and low concentration of ibuprofen at the site of reactivation and replication of latent virus. Alternatively, in the clinical setting, it is conceivable that ibuprofen may not have an effect on in vivo reactivation of latent herpes. PMID- 1312235 TI - A CA repeat 30-70 Kb downstream from the adenomatous polyposis coli (APC) gene. PMID- 1312236 TI - The 'other' sexually transmitted diseases. Chlamydial, herpes simplex virus, and human papillomavirus infections. AB - The incidence of sexually transmitted diseases continues to rise across the country. Because many cases are subclinical and asymptomatic, chlamydial, herpes simplex virus, and human papillomavirus (HPV) infections continue to spread at an alarming rate. These infections can lead to serious sequelae, such as pelvic inflammatory disease, infertility, and cervical dysplasia or carcinoma, so improved disease-control strategies are needed. Preventive efforts should include use of the latest diagnostic and therapeutic methods to uncover and eradicate subclinical chlamydial and HPV infections. In addition, notification of sexual partners should be encouraged. Education about prevention of sexually transmitted diseases should be incorporated into basic primary medical care for all sexually active patients. PMID- 1312237 TI - Suitability of using sieved or unsieved maize mash for production of "OGI"--a fermented cereal food. AB - Proximate analysis of sieved and unsieved maize mash revealed that there was a decrease in the protein and lipid content of the sieved maize mash as compared to that of the unsieved maize mash. Crude fibre and ash was completely absent in the sieved maize mash, while they were present in the unsieved mash. Chemical analysis of the fermented unsieved maize mash revealed an increase in the protein content from 9.9% (unfermented) to 13.4% after 3 days of fermentation, whereas the protein content of the sieved maize mash increased from 7.1% (unfermented) to 8.4% after the same period of fermentation. Furthermore, the results revealed that the protein content of the fermented unsieved maize mash was 32.1% higher than that of the fermented sieved maize mash indicating that the unsieved maize mash was of a better nutrient quality and should be preferred to sieved maize mash for use in "Ogi" production. PMID- 1312238 TI - Absorption of color additives and settling volume in water of blue-green alga, ishikurage (Nostoc commune). AB - The properties of ishikurage (Nostoc commune) and other algae were compared. Ishikurage and suizenji nori (Aphanothece sacrum) absorbed much more amaranth than others. They have a high settling volume (SV) in water. The high SV of ishikurage is attributable to its neutral detergent fiber (NDF). The acid detergent fiber (ADF) from the alga had a high amaranth absorption. However the absorption by the ADF did not explain the absorption by ishikurage. The results suggest that ishikurage may have a nutritional significance as a source of dietary fiber. PMID- 1312239 TI - Effect of full-fat or defatted rice bran on serum cholesterol. AB - Rice bran has been shown to lower serum cholesterol in hamsters. Leghorn cockerel chicks were fed 60% full-fat rice bran (FFRB) and corn/soy (CS) diets with 0.5% added cholesterol. Both diets contained 18% protein. All reported parameters are on blood serum. Significant differences (p less than 0.05) were found in total cholesterol (TC), triglycerides (TG), high-density and low-density lipoprotein cholesterol (HDL and LDL). In a second study, chicks were fed FFRB, defatted rice bran (DFRB), and CS diets balanced for 18% protein, 14.47% total dietary fiber and 10.78% lipid with 0.5% added cholesterol. Both TC and TG were significantly lower (p less than 0.05) in chicks fed FFRB and CS diets. Significant differences were found in HDL values for all diets with FFRB exhibiting the highest mean value (155 mg/dl) and CS exhibiting the lowest mean value (114 mg/dl). All diets were significantly different (p less than 0.05) in LDL, with mean values of 249, 318 and 275 mg/dl for FFRB, DFRB and CS, respectively. FFRB appears to increase HDL and to lower LDL in chicks, but does not always affect TC, whereas DFRB may increase all three serum lipid components. PMID- 1312240 TI - [Relation between 67-gallium scintigraphy and bronchoalveolar lavage- differential cell count and superoxide anion liberation--in patients with systemic scleroderma and systemic lupus erythematosus]. AB - The aim of the study was to determine the pulmonary 67-gallium uptake, bronchoalveolar lavage (BAL) cell differentiation and the activity of BAL cells, measured as release of superoxide anion (O2-), and to investigate the results whether there are relations. In 11 nonsmoking systemic scleroderma (SS) patients and 11 systemic lupus erythematosus (SLE) patients with lung involvement double sided BAL were performed, mainly in regions with increased 67-gallium uptake. Release of O2- was measured by INT-assey. BAL cell differentiation was in SS and SLE pathological in 68.2% without side-difference. In contrast to SS, O2(-) release in SLE depends on BAL cell differentiation and is most increased in normal BAL cell differentiation. There is no correlation between 67-gallium uptake and both BAL cell differentiation and O2(-)-release. The results suggest, that in contrast to SS, BAL cells in SLE with pathological differentiation are less activated than BAL cells with normal differentiation probable due to autoimmunological factors. Pulmonary 67-gallium scan and BAL seem to be independent from each other. PMID- 1312241 TI - Induction of bone in composites of osteogenin and porous hydroxyapatite in baboons. AB - A major goal of the combined effort of basic scientists and plastic and reconstructive surgeons is the development of novel bone substitutes based on osteogenic growth and differentiation factors with optimal delivery systems for skeletal repair. Osteogenin is a protein initiator of bone differentiation. The present study examined the osteogenic potential of osteogenin in combination with porous hydroxyapatite replicas obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. Bovine osteogenin, with an apparent molecular weight of 28 to 42 kDa, purified by hydroxyapatite-Ultrogel adsorption chromatography, heparin-Sepharose affinity chromatography, and HR Sephacryl S-200 molecular sieve chromatography, was delivered into rods of nonresorbable and resorbable hydroxyapatite replicas with an average porosity of 600 microns. A total of 48 rods were bioassayed for osteogenic activity by intramuscular implantation into eight adult baboons (Papio ursinus) as a prerequisite for clinical trials in humans. Bovine osteogenin fractions reconstituted with baboon insoluble collagenous bone matrix were implanted in an additional four adult baboons. Specimens were harvested at 30 and 90 days after implantation and subjected to histomorphometry and alkaline phosphatase activity determination. Differentiation of bone occurred in nonresorbable hydroxyapatite rods, both osteogenin-treated and controls. However, no bone formation was observed in resorbable rods, even in the presence of osteogenin. These results demonstrate that the surface and chemical characteristics of the substratum, independent of the osteogenic stimulus, have a profound influence on the morphogenesis of bone. The demonstration of bone induction in nonhuman primates with porous nonresorbable hydroxyapatite replicas and baboon insoluble collagenous bone matrix reconstituted with bovine osteogenin establishes the therapeutic potential of the principle of bone induction in craniofacial, periodontal, and orthopedic reconstructive surgery. PMID- 1312242 TI - [An unclear mediastinal space-occupying lesion]. PMID- 1312244 TI - Ontogeny of some neuropeptides in the primate brain. PMID- 1312243 TI - Neuropeptide Y and neuropeptide Y receptor subtypes in brain and peripheral tissues. PMID- 1312245 TI - Experimental complex partial seizures induced by a microinjection of kainic acid into limbic structures. PMID- 1312246 TI - Alpha melanocyte stimulating hormone (alpha-MSH) enhances eicosanoid production by bovine retinal pigment epithelium. AB - Explants of bovine eyes consisting of retina, with its underlying choroid and sclera (termed retinal explants) were maintained in organ culture in the absence or presence of alpha-melanocyte stimulating hormone (alpha-MSH) for up to 19 days. The conditioned media was collected twice a week and assayed for the following eicosanoids, prostaglandin E2 (PGE2) and prostacyclin. The addition of alpha-MSH to the incubation media resulted in a 1.5 fold enhancement in the production of both PGE2 and prostacyclin. This stimulatory effect diminished after 11 days. Additionally, the three tissue components comprising the retinal explants i.e. 1. neural retina 2. retinal pigment epithelium (RPE) with its underlying vascular layer (choroid) and 3. scleral tissue were separated and incubated in the presence or absence of alpha-MSH. Hormone treatment caused an enhanced eicosanoid production by RPE tissue alone, while its production by the neuronal retina and sclera was reduced or unaffected respectively. This demonstrates that the RPE layer is the source for the alpha-MSH induced eicosanoid production observed in the whole retinal explant. Our findings demonstrate, for the first time that alpha-MSH can stimulate prostaglandin production by RPE maintained in organ culture. PMID- 1312247 TI - Synthesis and contractile activity of new pseudopeptido and thioaromatic analogues of leukotriene D4. AB - Seven new pseudopeptido and thioaromatic leukotriene analogues were synthesized and their agonist-antagonist and binding activities investigated. The synthesis led to the pleasing observation that the analogue in which the cysteinyl-glycine moiety was replaced by a 6-mercapto-3-(E)-hexenoic acid, not only exhibited potent affinity (guinea-pig lung parenchyma, IC50: 5 x 10(-9) M) but also showed 30% of the LTD4 agonist activity (guinea-pig ileum, ED 50: 2.7 x 10(-9)) giving very important key information on LTD4 geometry to the receptor. This compound was the first stable new pseudopeptido-leukotriene with such agonist activity and should contribute to the understanding of the metabolism of leukotriene D4. In addition, inversion of chirality at C5 and C6 carbon atoms of the leukotriene chain or replacement of the cysteinyl-glycine moiety by a thioaromatic acid led to new weak antagonists of the LTD4. PMID- 1312248 TI - [Infection by human herpesvirus type 6: epidemiology, immunopathology and clinical implications]. AB - The human herpesvirus type 6 has been discovered recently and is the object of numerous investigations. Even though, its morphology is very close to the cytomegalovirus, its epidemiologic, immunopathologic and clinic characteristics are similar to the Epstein-Barr virus. Like the latter, HHV-6 persists latent in the host during all his live, frequently relapsed and is ubiquitous. Exanthema subitum in children and mononucleosis-like syndrome in adults have been attributed to acute HHV-6 infection. Under certain conditions, the development of chronic fatigue syndrome, some lymphoproliferative disorders and, perhaps, others diseases can be influenced by the persistent activity of this infection furthermore, HHV-6 can be a cofactor in infection with HIV and provokes a faster evolution and more severe illness. PMID- 1312249 TI - [Erythema multiforme and its relation to herpes simplex I and II]. PMID- 1312250 TI - [Blood transfusion and solid organ transplantation]. PMID- 1312251 TI - [Acquired hemoglobin H disease in the early stage of erythroleukemia]. AB - At the onset of erythroleukemia, the patient, a 74-year-old Swiss male, was also found to have microcytic-hypochromic anemia (Hb: 82 g/l, MCV: 69 fl, MCH: 21 pg). Further laboratory examinations revealed reduced hemoglobin stability, a hemoglobin H fraction of 3.0% on cellulose acetate-electrophoresis, and an abundance of hemoglobin H inclusion bodies in red cells. These findings, as well as the Swiss origin of the patient and his age at the onset of the disease, were consistent with acquired hemoglobin H disease. In addition to genetic hemoglobin H disease, acquired hemoglobin H disease was reported to be associated with myelodysplastic and myeloproliferative syndrome, or erythroleukemia and acute myelogenous leukemia. The literature contains fewer than 50 cases. It is suggested that the molecular basis of this rare disease involves a gene in trans to the alpha-globin genes reducing the expression of all four alpha-globin genes to approximately 10% of normal activity. PMID- 1312252 TI - Florida dentist case: research affiliation and ethics. PMID- 1312253 TI - Analytical chemists push the cellular envelope. PMID- 1312254 TI - Parting blast from AIDS official. PMID- 1312255 TI - Molecular characterization of helix-loop-helix peptides. AB - A class of regulators of eukaryotic gene expression contains a conserved amino acid sequence responsible for protein oligomerization and binding to DNA. This structure consists of an arginine- and lysine-rich basic region followed by a helix-loop-helix motif, which together mediate specific binding to DNA. Peptides were prepared that span this motif in the MyoD protein; in solution, they formed alpha-helical dimers and tetramers. They bound to DNA as dimers and their alpha helical content increased on binding. Parallel and antiparallel four-helix models of the DNA-bound dimer were constructed. Peptides containing disulfide bonds were engineered to test the correctness of the two models. A disulfide that is compatible with the parallel model promotes specific interaction with DNA, whereas a disulfide compatible with the antiparallel model abolishes specific binding. Electron paramagnetic resonance (EPR) measurements of nitroxide-labeled peptides provided intersubunit distance measurements that also supported the parallel model. PMID- 1312256 TI - The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. AB - The fms-like tyrosine kinase (Flt) is a transmembrane receptor in the tyrosine kinase family. Expression of flt complementary DNA in COS cells conferred specific, high-affinity binding of vascular endothelial growth factor, also known as vascular permeability factor (VEGF-VPF), a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation. Expression of Flt in Xenopus laevis oocytes caused the oocytes to release calcium in response to VEGF-VPF. These findings show that flt encodes a receptor for VEGF-VPF. PMID- 1312257 TI - Encapsulation of proteins in transparent porous silicate glasses prepared by the sol-gel method. AB - Novel sol-gel synthetic techniques were used to immobilize copper-zinc superoxide dismutase (CuZnSOD), cytochrome c, and myoglobin (Mb) by encapsulation in stable, optically transparent, porous silica glass matrices under mild conditions such that the biomolecules retained their characteristic reactivities and spectroscopic properties. The resulting glasses allowed transport of small molecules into and out of the glasses at reasonable rates but nevertheless retained the protein molecules within their pores. Chemical reactions of the immobilized proteins could be monitored by means of changes in their visible absorption spectra. Silica glasses containing the immobilized proteins were observed to have similar reactivities and spectroscopic properties to those found for the proteins in solution. For example, encapsulated CuZnSOD was demetallated and remetallated, encapsulated ferricytochrome c was reduced and then reoxidized, and encapsulated met Mb was reduced to deoxy Mb and then reacted either with dioxygen to make oxy Mb or with carbon monoxide to make carbonyl Mb. PMID- 1312258 TI - Association of cdk2 kinase with the transcription factor E2F during S phase. AB - The transcription factor E2F controls the expression of several proliferation related genes and is a target of the adenovirus E1A oncogene. In human cells, both cyclin A and the cdk2 protein kinase were found in complexes with E2F. Although the total amounts of cdk2 were constant in the cell cycle, binding to E2F was detected only when cells entered S phase, a time when the cdk2 kinase is activated. These data suggest that the interaction between cdk2 and E2F requires an active kinase that has cyclin A as a targeting component. PMID- 1312259 TI - Major setback for Alzheimer's models. PMID- 1312260 TI - Radiotherapeutic palliation of spinal epidural compression in small-cell lung cancer. AB - Sixteen patients with spinal epidural compression by metastatic small-cell lung cancer were given radiotherapy for palliation. Lower limb motor deficit was the most prominent clinical manifestation. Neurologic dysfunction was commonly present for more than 48 hours before the diagnosis of compression. Median interval between diagnosis of lung cancer and epidural tumor was 8.5 months. Twelve percent of the patients survived for 1 year after diagnosis of epidural compression. Radiotherapy gave significant pain relief to eight (89%) of the symptomatic individuals. Among those whose status could be assessed, one third of the initially nonambulatory patients (n = 9) were able to walk again. Anal or bladder sphincter or sensory disturbance did not improve in four persons. Radiotherapy for spinal epidural compression in small-cell lung cancer, though not curative, is highly effective in the relief of pain and may ameliorate limb motor dysfunction in some patients. PMID- 1312261 TI - Reconstitution of enzymatic activity in hepatocytes of phenylalanine hydroxylase deficient mice. AB - Phenylketonuria (PKU) is a metabolic disorder secondary to a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). The recent creation of a mouse strain for PAH deficiency has provided an excellent model system to explore the possibility of its phenotypic correction by hepatic gene therapy. A recombinant retrovirus containing the mouse PAH cDNA under the transcriptional control of the human CMV promoter was constructed and used to transduce hepatocytes isolated from PAH-deficient mice. Viral-transduced hepatocytes produced dramatically higher levels of mouse PAH mRNA as compared to control mock-infected hepatocytes. The PAH mRNA was translated efficiently into PAH protein that is capable of converting phenylalanine to tyrosine in vitro. These results demonstrate that the PAH-deficient mouse hepatocytes can be readily reconstituted by retroviral mediated gene transduction, which is a crucial step towards somatic gene therapy for PKU. PMID- 1312262 TI - Intracranial melanotic neuroectodermal tumor of infancy: two case reports. AB - Two childhood cases of intracranial melanotic neuroectodermal tumor, one benign and one malignant, are presented. The clinical, radiologic, and pathologic features of these cases are described and the relevant literature is reviewed. PMID- 1312263 TI - Steady-state pharmacokinetics of rufloxacin in elderly patients with lower respiratory tract infections. AB - The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6-9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 +/- 1.06 (mean +/- SEM) micrograms/ml and was reached in 4.3 +/- 0.8 h after the first administration. The elimination half-life was 28.7 +/- 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 +/- 14 micrograms/h/ml after the first dose. On the last day of observation it increased to 155 +/- 28 micrograms/h/ml, with a mean extent of accumulation of 2.3 +/- 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects. PMID- 1312264 TI - Release of tumor necrosis factor-alpha from bovine alveolar macrophages stimulated with bovine respiratory viruses and bacterial endotoxins. AB - The release of tumor necrosis factor-alpha (TNF-alpha) from cultured bovine alveolar macrophages (BAM) was evaluated following stimulation of BAM with bovine herpesvirus-1 (BHV-1), parainfluenza-3 (PI-3) virus, bovine respiratory syncytial virus (BRSV), Escherichia coli 0111:B4 endotoxin, Pasteurella haemolytica type 1 endotoxin, Pasteurella multocida endotoxin, and virus/endotoxin combinations. A cytotoxic assay system using Georgia bovine kidney cells as targets was used to measure TNF-alpha activity. The cytotoxic activity was neutralized by an anti human TNF-alpha monoclonal antibody. Stimulation of BAM with 1 median tissue culture infectious dose (TCID50) of live or ultraviolet (UV)-inactivated PI-3 virus/cell resulted in release of TNF-alpha in significantly (P less than 0.05) higher amounts than sham-induced BAM. The quantities of TNF-alpha released after live or UV-inactivated BHV-1 or BRSV induction were not significantly higher than sham-induced BAM. E. coli 0111:B4, P. haemolytica type 1 and P. multocida endotoxins stimulated TNF-alpha release in a dose-dependent manner. Sequential exposure of BAM to 1 TCID50 per cell of either live BHV-1, PI-3 virus or BRSV and then 5 micrograms ml-1 of either E. coli 0111:B4, P. haemolytica type 1 or P. multocida endotoxin caused a significant (P less than 0.05) reduction in detectable TNF-alpha in seven of nine virus/endotoxin combinations tested, when compared with 5 micrograms ml-1 of endotoxin alone. Parainfluenza-3 virus/endotoxin combinations stimulated higher TNF-alpha release when compared with other virus/endotoxin combinations. Five out of six test animals had serum neutralizing antibodies to PI-3 virus, one out of six had serum-neutralizing antibodies to BHV-1, and two out of six had serum-neutralizing antibodies to BRSV, suggesting a possible relationship between serum neutralizing antibodies and TNF-alpha release from in vitro cultivated BAM. PMID- 1312265 TI - Maturation of poliovirus capsid proteins. PMID- 1312266 TI - Enhanced neurovirulence of tick-borne orbiviruses resulting from genetic modulation. AB - The genome of orbiviruses (Reoviridae family) comprises 10 segments of double stranded RNA. The fourth largest segment of the tick-borne Kemerovo (KEM) group orbiviruses is the genetic determinant of neurovirulence in experimentally infected mice, and segment 6 determines serotype. Reassortant viruses derived from a cross between two KEM-related viruses, Great Island (GI) and Wexford (WEX), that had the heterotypic gene combination W4G6 (segment 4 of WEX virus and segment 6 from GI virus) were nonpathogenic in mice. This apparent genetic modulation of neurovirulence may have resulted from steric interaction between the two outer capsid proteins of nonpathogenic reassortants. Further data are consistent with this hypothesis. Reassortants generated from additional KEM group viruses showed various degrees of enhanced neurovirulence in terms of their PFU/LD50 (ratio of infectivity in cell culture and in mice) and ASTmax (the average survival time at the highest virus dilution resulting in 100% mortality). Some reassortants were more pathogenic than either of their parental viruses. The results indicate that the gene determining neurovirulence dictates ASTmax, and the PFU/LD50 is a measure of the interaction between the products of the gene determining neurovirulence and that determining serotype. The nonpathogenic phenotype of a low passage isolate (St. Abb's 84-34 virus), derived from a single tick, generated neurovirulent reassortants. This result indicates that genetic modulation of KEM group viruses may occur in nature. PMID- 1312267 TI - Budding site of Sendai virus in polarized epithelial cells is one of the determinants for tropism and pathogenicity in mice. AB - Wild-type Sendai virus fusion (F) glycoprotein requires trypsin or a trypsin-like protease for cleavage-activation in vitro and in vivo, respectively. The virus is pneumotropic in mice and buds at the apical domain of bronchial epithelial cells. On the other hand, the F protein of the protease-activation host range mutant, F1 R, is cleaved by ubiquitous proteases present in different cell lines and in various organs of mice. F1-R causes a systemic infection in mice and the mutant buds bipolarly at the apical and basolateral domains of infected epithelial cells. The enhanced cleavability of the F protein of F1-R has been shown to be a primary determinant for pantropism. Additionally, it has been postulated that bipolar budding of F1-R is required for the systemic spread of the virus and it has been attributed to mutations in the matrix (M) protein of F1-R (Tashiro et al., Virology 184, 227-234, 1991). In this study protease-activation mutants (KD series) were isolated from wild-type virus. They were revealed to bud at the apical domain, and the F protein was cleaved by ubiquitous proteases in mouse organs. The KD mutants were exclusively pneumotropic in mice following intranasal infection, whereas they caused a generalized infection when inoculated directly into the circulatory system. Comparative nucleotide sequence analysis of the F gene of the KD mutants revealed that the deduced amino acid substitutions responsible for enhanced cleavability of the F protein occurred removed from the cleavage site. Mutations were not at all found in the M gene of the KD mutants analyzed, in support of the role of the M protein of F1-R and of a revertant T-9 derived from the latter in bipolar budding. These results suggest that bipolar budding is necessary for the systemic spread of F1-R from the lungs and that apical budding by wild-type virus and the KD mutants leads to respiratory infections. Differential budding at the primary target of infection, in addition to the cleavage-activation of the F protein in mouse organs, is therefore also a determinant for tropism and pathogenicity of Sendai virus in mice. PMID- 1312268 TI - Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16-associated invasive cervical cancer. AB - Transforming proteins E6 and E7 of human papillomaviruses (HPVs) are consistently expressed in HPV-associated cervical cancers. In ELISA with four HPV-16 E6-E7 peptides, patients with HPV-16-associated invasive cervical cancer (group 1) had a greater seroreactivity than all other groups, which included patients with HPV 16-associated cervical intraepithelial neoplasia, invasive cervical cancer patients without HPVs, and unaffected controls. A larger proportion of group 1 sera, as compared to sera of all other groups, was reactive with at least one peptide (49% vs 17-27%), and with two or more peptides (22% vs 0-6%). A clear difference between group 1 and all other groups was also found for high ELISA absorbance values to at least one peptide (22% vs 0-8%). This high seroreactivity of group 1 sera was confirmed by a radioimmunoprecipitation assay with in vitro transcribed and translated HPV-16 E7 protein. Sera from 50% of group 1 but only 3% of controls were reactive in this test. Antibodies to HPV-16 E6 and E7 proteins appear to be virus-specific and disease state-specific markers of HPV associated cervical cancer. PMID- 1312269 TI - Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses. AB - A comparison of the sequence of the dengue-2 16681 virus with that of the candidate vaccine strain (16681-PDK53) derived from it identified 53 of the 10,723 nucleotides which differed between the strains. Nucleotide changes occurred in genes coding for all virion and nonvirion proteins, and in the 5' and 3' untranslated regions. Twenty-seven of the nucleotide changes resulted in amino acid alterations. The greatest amino acid sequence differences in the virion proteins occurred in prM (2.20%; 2/91 amino acids) followed by the M protein (1.33%; 1/75 amino acids), the C protein (0.88%; 1/114 amino acid), and the E protein (0.61%; 3/495 amino acids). Differences in the amino acid sequence of nonvirion proteins ranged from 1.51% (6/398 amino acids) in NS4 to 0.33% (3/900 amino acids) in NS5. The encoded protein sequences of 16681-PDK53 were also compared with the published sequences of other flaviviruses to obtain a detailed classification of 17 flaviviruses using the neighbor-joining tree method. The analyses of the sequence data produced dendrograms which supported the traditional groupings based on serological evidence, and they suggested that the flaviviruses have evolved by divergent mutational change and there was no evidence of genetic recombination between members of the group. Comparisons of the sequences of the flavivirus polymerase and helicase-like proteins (NS5 and NS3, respectively) with those from other viruses yielded a classification of the flaviviruses indicating that the primary division of the flaviviruses was between those transmitted by mosquitoes and those transmitted by ticks. PMID- 1312270 TI - DNA binding activity is required for EBNA 1-dependent transcriptional activation and DNA replication. AB - Epstein-Barr virus nuclear antigen 1 (EBNA 1) has been shown to be a sequence specific DNA binding protein that is required for the replication of episomal elements carrying the viral origin of DNA replication, oriP, as well as for the activation of a specific transcriptional enhancer. We have constructed and analyzed a series of deletion and nonsense mutants in a cloned copy of the EBNA 1 gene and have tested mutant peptides for the ability (a) to bind to a synthetic oligonucleotide containing a consensus EBNA 1 binding site, (b) to activate the EBNA 1-specific enhancer, and (c) to drive replication of an oriP-bearing plasmid in a transient replication assay. The presence of a DNA binding domain in the carboxy-terminal third of the protein was confirmed. Interestingly, neither the acidic tail nor the Gly-Ala copolymer of EBNA 1 contributes significantly to binding. In addition to sequences in the carboxy-terminal portion of the protein, our data indicate that sequences in the amino-terminal portion of the polypeptide affect the binding of EBNA 1 to its target sequence. Further, we show that EBNA 1 binds to its recognition sequence as a dimer. Results of transient expression assays indicate that the ability of EBNA 1 species to activate the transcriptional enhancer and to drive the replication of oriP plasmids is directly dependent on the ability of the polypeptides to bind to the EBNA 1 consensus binding sequence. PMID- 1312271 TI - Effective vaccination against papilloma development by immunization with L1 or L2 structural protein of cottontail rabbit papillomavirus. AB - Immunization of rabbits with either L1, the major structural protein, or L2, a minor structural protein of cottontail rabbit papillomavirus (CRPV), protected against challenge with the virus. Neutralizing antibodies were elicited by both the L1 and L2 trpE fusion proteins. Neutralization with anti-L1 serum, however, was more efficient than with anti-L2 serum. In contrast, when tested on Western blots the immune response to L2 was stronger than to L1. Rabbits were also protected against CRPV infection by immunization with L1 expressing recombinant vaccinia virus. Sera from two of three rabbits immunized with recombinant vaccinia virus were negative on Western blots but all three were positive in ELISA's with nondenatured fusion protein or in immunoprecipitations. The results suggest that both the viral structural proteins, L1 and L2, merit consideration in the development of a vaccine against papillomavirus. PMID- 1312272 TI - A novel quasi-viral agent, MaTu, is a two-component system. AB - MaTu is a quasi-viral agent presumably derived from a human mammary tumor. In some respects it resembles classical viruses and in some the "slow viruses," and in others it is different from both. Using monoclonal antibodies (Mabs), we showed that it is a two-component system. One part of the complex, MX, is exogenous; it is manifested by a protein, p58X, which is a cytoplasmic antigen and it reacts with some natural sera of man and of various animals. The other component, MN, is endogenous to human cells. This is manifested by a twin protein(s), p54/58N, localized on the cell surface and in the nucleus. This protein is absent in rapidly growing, sparse cultures of HeLa, but it is inducible either by keeping the cells in dense cultures or, more efficiently, by infecting them with MX. Both inducing factors are synergistic. Only p54/58N is associated with virions of vesicular stomatitis virus (VSV), reproduced in MaTu infected HeLa. This suggests that MN is responsible for complementation of VSV mutants and for the formation of the VSV (MaTu) pseudotype. Both p54/58N peptides are glycosylated and they form oligomers linked by disulfidic bonds; p58X is not glycosylated and it does not form S-S-linked oligomers. PMID- 1312273 TI - Acute inflammatory response to cowpox virus infection of the chorioallantoic membrane of the chick embryo. AB - The chick embryo chorioallantoic membrane was used to study the acute inflammatory response in the absence of contributions from the immune system. In preliminary experiments, lesions of wild-type cowpox virus strain Brighton (CPV BR) and a 38K gene deletion mutant of CPV-BR (CPV-BR.D1) were compared with vaccinia virus (strains WR and Copenhagen), fowlpox virus, laryngotracheitis virus, and infectious tenosynovitis virus, and were ranked for degree of induced inflammation. The maximal and minimal inflammatory responses were observed with CPV-BR.D1 and CPV-BR viruses, respectively. CPV-BR.D1 lacks a 38K gene which encodes an anti-inflammatory 38-kDa protein that has homology to SERPINs. The kinetics and character of the inflammatory response were examined further in the wild-type CPV-BR and mutant CPV-BR.D1 infections using cell counts, electron microscopy, and assays for inflammatory cell activation. CPV-BR virus infection rapidly spread through the ectoderm, uniformly infecting all cells with the production of large amounts of virions and viral-induced cytopathic effect, but evoking little or no inflammatory response until 144 hr p.i. The CPV-BR.D1 infection, on the other hand, was rapidly contained by a dexamethasone-sensitive inflammatory response mainly of activated heterophils which was advanced by 36 hr p.i. Both infections resulted in disseminated disease with similar numbers of liver lesions and only a slight difference in the LD50, with the CPV-BR.D1 values being higher than that for CPV-BR virus. In this model, the acute inflammatory response alone is unable to prevent disseminated disease and associated mortality. PMID- 1312274 TI - An SV40 transformation revertant due to a host mutation: isolation and complementation analysis. AB - We have isolated an SV40 transformation revertant cell line, CL1L, by selection for normal cells whose growth is inhibited under low serum conditions. This line expresses a single, wild-type copy of large T antigen, yet is not transformed. It is not retransformable by transfection of SV40 DNA or infection with a recombinant retrovirus encoding large T antigen. Resistance to transformation therefore appears to be due to a cellular mutation. Fusion of CL1L cells to normal 3T3 cells or SV40-transformed cells results in somatic cell hybrids that are transformed, indicating that resistance is recessive. In addition, fusion of CL1L cells to another SV40 transformation-resistant line, A27, results in transformed hybrids, indicating the existence of discrete complementation groups with respect to SV40 transformation. PMID- 1312275 TI - Heterogeneity in state and expression of viral DNA in polyoma virus-induced tumors of the mouse. AB - We have examined the state and expression of polyoma viral DNA in representative epithelial and mesenchymal tumors, using a combination of biochemical and in situ methods. Results showed wide variations among tumor types and also in different regions within individual tumors, with respect to copy number of viral DNA, presence or absence of deletions, and expression of early and late viral proteins. Epithelial tumors showed the greatest heterogeneity. High copy free viral DNA, frequently with deletions, was found in all such tumors. A portion of free viral DNA was recoverable as transcriptionally active minichromosomes. Three distinct subpopulations of cells were distinguished by in situ analyses. Type 1 cells showed high copy free viral DNA and expressed the major viral capsid protein VP1; these cells appeared to be at various stages of productive (lytic) viral infection. Some productively infected cells were able to undergo mitosis; in a portion of these cells, VP1 was found in close association with the mitotic spindle. Type 2 cells contained high copy free DNA but did not express VP1; by some unknown mechanism, these cells manifest a post-replication block to late gene expression and lytic infection. Type 3 cells contained only low copy, presumably integrated, viral DNA and expressed no VP1; they thus resemble cells transformed in vitro by the virus. Epithelial tumors contained variable mixtures of these subpopulations, while mesenchymal tumors were composed of Type 3 cells only. Differences in virus-cell interactions are discussed in terms of their possible implications in tumor development. PMID- 1312276 TI - Phylogenetic analysis of a coxsackievirus A24 variant: the most recent worldwide pandemic was caused by progenies of a virus prevalent around 1981. AB - Nucleotide substitutions in the viral-encoded proteinase 3C (3Cpro) region (549 nucleotides) of the RNA genome of a coxsackievirus A24 variant (CA24v), one of the agents causing acute hemorrhagic conjunctivitis (AHC), were studied using 32 isolates collected from the Eastern hemisphere in 1970-1989. Based on regression analysis of nucleotide differences among isolates, the nucleotide substitution rate of CA24v 3Cpro was estimated to be 3.7 x 10(-3)/nucleotide/year. A phylogenetic tree constructed by the modified unweighted pair group method using arithmetic averages (UPGMA) indicated that CA24v had evolved from a common ancestor which appeared in one focal place in November 1963 +/- 21 months, about 7 years before the first isolation of CA24v in Singapore. The tree also revealed that all the recent epidemic isolates in 1985-1989 including Asian and Ghanian strains diverged from each other after 1981. This finding is consistent with the evidence that AHC due to CA24v had been confined to Southeast Asia and the Indian subcontinent until 1985, then suddenly and explosively spread to other areas where no CA24v isolations had been reported. PMID- 1312277 TI - Mouse Mx2 protein inhibits vesicular stomatitis virus but not influenza virus. AB - Some but not all known Mx proteins possess intrinsic antiviral activity. The mouse genome contains two related interferon-regulated genes, designated Mx1 and Mx2. Mx1 codes for a nuclear 72-kDa protein which selectively interferes with the multiplication of influenza viruses. The Mx2 gene is crippled by a mutation in commonly used laboratory mouse strains and, hence, the antiviral potential of the Mx2 protein was unknown. We have corrected the frameshift mutation in a cloned Mx2 cDNA by site-directed mutagenesis. Expression of the repaired Mx2 cDNA in Swiss mouse 3T3 cells gave rise to an 80-kDa cytoplasmic protein that cross reacted with antibodies to other Mx proteins. In contrast to the cases of mouse Mx1 and human Mx proteins, permanent cell lines were extremely unstable with respect to Mx2 expression. Analysis at the single-cell level revealed that mouse Mx2 conferred to the transfected cells a high degree of resistance to vesicular stomatitis virus, but had no inhibitory effect on influenza virus. The antiviral potential of mouse Mx2 is thus similar to that of rat Mx2 protein. PMID- 1312278 TI - Sequence determination of cDNA clones of transcripts from the tumor-associated region of the Marek's disease virus genome. AB - The number of 132-bp tandem direct repeats within the long inverted repeat region of the Marek's disease virus type 1 (MDV1) genome increases concomitantly with the loss of oncogenicity during serial passages in cultured cells. Twelve clones carrying the 132-bp sequence were isolated from a cDNA library constructed from chicken embryo fibroblasts infected with the MDV1 Md5 strain. Through sequence analysis of a cDNA clone and primer extension analysis, the corresponding mRNA was found to be a linear transcript which included the two 132-bp tandem direct repeats. Two open reading frames were found in this transcript. One had a week homology with v-fms. The other should increase its size concomitantly with expansion of the 132-bp tandem direct repeat. PCR analysis of both cDNA clones and RNA gave amplified products which were as large as that produced from the genomic clone, indicating that a majority of mRNA from this region is composed of unspliced transcripts. PMID- 1312279 TI - Myristate modification does not function as a membrane association signal during poliovirus capsid assembly. AB - The myristate moiety is required for poliovirus assembly. Unlike most other myristoyl-modified proteins, which are membrane associated, no specific membrane association of the poliovirus capsid proteins or assembly intermediates was observed. Furthermore, no apparent differences in membrane association of wild type and myristoylation deficient mutant viruses could be detected in this analysis. Thus, during poliovirus assembly, the myristate modification is not required as a membrane targeting signal but is more likely involved in structural interactions between protomer subunits. PMID- 1312280 TI - Activation of bovine immunodeficiency-like virus expression by bovine herpesvirus type 1. AB - Bovine immunodeficiency-like virus (BIV) is a recently identified lentivirus that infects cattle. The virus has structural and genetic similarities to human HIV. The present study demonstrates that BIV can be activated by bovine herpesvirus type 1 (BHV-1), a pathogen frequently associated with cattle diseases. Activation of BIV expression can be detected as increased BIV reverse transcriptase activity, increased in the number of syncytia induced by BIV, and increased in the steady state level of BIV-specific RNA upon BHV-1 super-infection. Additional transactivation studies using the BIV-LTR (long terminal repeat) were conducted. The BIV-LTR was linked to the chloramphenicol acetyl transferase gene (CAT) and transfected into bovine cell cultures in order to quantitate the levels of BIV LTR expression. When the transfected cells were infected by BHV-1, there was an increase in CAT expression, indicating transactivation of the BIV-LTR by BHV-1. Most of the transactivation activities were abolished with an LTR construct that has deleted the NF-kappa B-like sequence located in the U3 region of the LTR. In order to further demonstrate that activation of the BIV-LTR involves factors that may bind to the LTR sequences, gel retardation assays were carried out using the BIV-LTR U3 region as probe. Our results showed that BHV-1 infection resulted in an induction of factor(s) that binds to the NF-kappa B-like sequence on the BIV LTR. This suggests that transactivation of BIV by BHV-1 may be mediated by a bovine NF-kappa B-like protein that binds to the target sequence in the BIV promoter region. PMID- 1312281 TI - Expression of cDNA encoding the Sendai virus hemagglutinin-neuraminidase gene: characterization of wild-type and mutant gene products. AB - Cloned cDNA encoding the Sendai virus (SV) hemagglutinin-neuraminidase (HN) envelope glycoprotein was expressed in cultured cells in two ways: (I) infection with HN-expressing recombinant vaccinia virus, or (II) transfection with a plasmid with T7 promoter and termination sequences flanking the HN gene, with intracellular T7 RNA polymerase supplied by coinfection with recombinant vaccinia virus that expresses the enzyme. The HN expressed was indistinguishable from the authentic SV protein in antigenicity, cell surface location, and formation of oligomeric structures. In addition, HN expressed from cDNA functioned normally in both hemadsorption and neuraminidase activities. The usefulness of cDNA expression for analyzing HN structure and function was evaluated by mutating the HN cDNA and observing the consequences for HN protein activity. Since previous work indicated that the lysine residue at position 461 is important for the neuraminidase activity of HN, we used site-directed mutation to produce HN protein with this lysine residue changed to glutamic acid. The mutated HN had neuraminidase activity with significantly increased thermal stability, indicating that residue 461 may be essential to the protein's conformation. PMID- 1312282 TI - Comparison of the nonstructural protein, NS3, of tick-borne and insect-borne orbiviruses. AB - The complete nucleotide sequence of the smallest RNA segment (segment 10) of Broadhaven (BRD) virus, a tick-borne orbivirus, was determined from a full-length cDNA clone. The genome segment is 702 nucleotides in length and has a coding capacity for two proteins of either 205 or 199 amino acids, having net charges of +16.5 and +17.5, respectively, at neutral pH. Comparison of the sequence of RNA segment 10 of BRD, bluetongue, African horse sickness, and Palyam viruses revealed amino acid homology of 20 to 30% between the four orbiviruses, with one conserved region of 40 to 50% homology which, in segment 10 of BRD virus, is found between residues 26 and 71. PMID- 1312283 TI - [Clinical practice with focus on oncology]. PMID- 1312284 TI - The cervical Papanicolaou smear: bacterial infection and the Bethesda System. PMID- 1312285 TI - Low-grade cribriform ductal carcinoma in situ of the breast. Fine needle aspiration cytology in three cases. AB - This paper presents the cytologic features of fine needle aspiration biopsy specimens from three cases of ductal carcinoma in situ characterized by small and uniform tumor cells growing in a predominantly cribriform pattern without comedo necrosis (low-grade cribriform ductal carcinoma in situ). On cytology, most of the tumor cells were clustered in three-dimensional ductal structures. Occasionally in the clusters the tumor cells were seen bordering central lumina, quite similar to the architecture in histology. A few single tumor cells and no myoepithelium were seen. The background was clear or slightly hemorrhagic, without necrosis. The tumor cells were uniform and had a cylindroid shape, with round or oval nuclei. Morphometrically the mean largest nuclear diameter was 1.5 1.6 times that of a red blood cell. The chromatin was finely granular, with a minute nucleolus and slight condensation along the nuclear membrane. In cut sections all three tumors showed strong immunoreactivity for neuron-specific enolase. Unless the cribriform growth pattern is recognized in the smear, the cytologic diagnosis of this entity is difficult. PMID- 1312286 TI - Choroid plexus papilloma. Report of a case with cytologic differential diagnosis. AB - The cytopathologic features of choroid plexus papilloma observed in the ventricular fluid of a 9-month-old boy are reported and compared with other pediatric central nervous system neoplasms. The cytologic features of choroid plexus papilloma are similar to those of normal choroid plexus and may be difficult to distinguish from those of a well-differentiated papillary ependymoma. However, the cell clusters are distinct from those associated with choroid plexus carcinoma and primitive neuroectodermal tumors. PMID- 1312287 TI - A computer-assisted automatic method for myelinated nerve fiber morphometry. AB - This paper describes a computer-assisted automatic method developed for myelinated nerve fiber morphometry. IBAS image analysis system was used. One micron thick sections of sural nerve were stained with p-phenylenediamine. Dark myelin sheaths, standing out against a pale background, were identified by a binary transformation of the computer-stored image. Different parameters of the fibers as well as of the axons can be measured. The automatic system allows operator-interactive manipulation, if required, to avoid inclusion of wrong histologic structures. A large spectrum of statistics facilities are available. We performed a comparison between automatic and semi-automatic analysis. Measurements resulted virtually overlapping, but time was three to four times shorter with automatic procedure. The method here described is accurate and reliable, and permits economy of time and effort. PMID- 1312288 TI - Compressive bilateral peroneal neuropathy: serial electrophysiologic studies and pathophysiological remarks. AB - A case of bilateral common peroneal neuropathy following prolonged squatting is reported. Serial peroneal conduction velocities with analysis of compound muscle action potential (CMAP) amplitude, area and duration performed at Days 1, 2, 5, 7, 14, 21, 37, 80 showed conduction block localized at the fibular head which lasted 14 days and paralleled clinical conditions. Axonal loss coexisted as indicated by amplitude reduction of CMAP from peroneal nerve stimulation at the ankle which reached the lowest values at Day 7. Excessive temporal dispersion, as indicated by abnormal increased duration of the CMAP from stimulation above the fibular head, was never detected. Conduction velocity in the segment across the fibular head was reduced as long as conduction block was present, due to preferential block of large diameter, fast conducting, fibers. The rapid resolution of conduction block and the absence of temporal dispersion suggest that compressive conduction block is not necessarily due to demyelination. Mechanical factors or ischemic-metabolic mechanisms might play a role. PMID- 1312289 TI - Epstein-Barr virus in B lymphocytes: viral gene expression and function in latency. PMID- 1312290 TI - The role of Raf-1 phosphorylation in signal transduction. PMID- 1312291 TI - Regulation of muscle cell growth and differentiation by the MyoD family of helix loop-helix proteins. AB - The skeletal muscle cell system provides a powerful model for exploring the mechanistic basis for the antagonism between cell growth and differentiation. The recent identification of the MyoD family of muscle-specific transcription factors now offers opportunities to dissect at the molecular level of the mechanisms through which defined cell type-specific transcription factors can activate an entire differentiation program as well as to unravel the mechanisms through which growth factor and oncogenic signals can disrupt cellular differentiation. Because the mechanisms for growth factor signaling and induction of cell proliferation are conserved in diverse cell types, it is tempting to speculate that the molecular mechanisms responsible for the antagonism between cell proliferation and differentiation in muscle cells are also operative in other cell types. Resolution of this question, however, must await identification of the regulatory factors that specify cell fate in other lineages. PMID- 1312292 TI - [Clinical and bacteriological study of sparfloxacin on bacterial prostatitis]. AB - Sparfloxacin (SPFX), a new oral quinolone antimicrobial, was studied for the bacterial response, pharmacokinetics and clinical efficacy in the treatment of bacterial prostatitis. The minimum inhibitory concentration (MIC) values for 48 strains isolated from expressed prostatic secretion were measured. The values for 8 out of 12 strains of S. epidermidis were below 0.05 microgram/ml and those for all 6 strains of E. coli were below 0.025 microgram/ml. The SPFX concentrations in prostatic fluid (PF) were 0.33 to 0.49 microgram/ml at 1 to 3 hours after oral administration of 200 mg, the PF/serum ratio being 1.15 to 1.47. SPFX was administered at a dose of 200 to 400 mg daily for an average of 14.1 days to 14 patients with prostatitis (5, acute: 9, chronic). The clinical efficacy judged by physician in charge was effective in 12 cases with an efficacy rate of 85.7%. The bacterial eradication rate was 93.3% (14/15 strains), and eradication was complete in all 7 cases infected with gram-negative rods. SPFX-related abnormal laboratory values were observed in one case with transient increase of glutamic oxalacetic transaminase, glutamic-pyruvic transaminase and alkaliphosphatase activities, and decrease of platelet. As side effects, one case with gastrointestinal symptoms and the other case with photosensitivity skin rash accompanied by sensory abnormality of palms were observed. The abnormal values or side effects in these patients recovered to normal or disappeared after completion of the treatment without any treatments. In view of the higher concentrations in PF than the MIC values with long remaining in the tissues, SPFX is considered to be effective in the treatment of bacterial prostatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312293 TI - Percutaneous transaxillary catheter insertion for hepatic artery infusion chemotherapy. PMID- 1312294 TI - High-density hepatocellular carcinoma on unenhanced CT. PMID- 1312295 TI - Comparative properties of angiotensin-converting enzyme inhibitors: relations with inhibition of tissue angiotensin-converting enzyme and potential clinical implications. AB - This review summarizes the evidence indicating that local synthesis of angiotensin II, and interference with this process by inhibition of angiotensin converting enzyme (ACE), may be important in the treatment of hypertension. Inhibition of tissue converting enzyme generally has a stronger correlation with the hemodynamic effects of ACE inhibitors than inhibition of ACE in plasma. Reported differences in the ability of ACE inhibitors to penetrate tissues and to bind to the converting enzyme may be closely related to the relative lipophilicity of these agents. Finally, correlation of data from clinical studies with results provided by laboratory experimentation suggests that the efficacy of different ACE inhibitors in hypertensive patients may be predicted from differences among the actions of these drugs in vitro and in whole animals. PMID- 1312296 TI - Angiotensin-converting enzyme in renal and cerebral tissue and implications for successful blood pressure management. AB - In addition to the classic circulating renin-angiotensin system, increasing evidence supports the existence of local tissue renin-angiotensin systems (vascular, cardiac, kidney, and brain) that appear to participate in cardiovascular homeostasis and in the pathogenesis of cardiovascular disorders via multiple autocrine and paracrine functions. Components of local systems have been detected in cardiovascular tissues. Studies with angiotensin-converting enzyme (ACE) inhibitors provide further evidence of the existence and importance of tissue renin-angiotensin systems. The blood pressure-lowering effect of quinapril, for example, correlated better with inhibition of tissue ACE (aorta) than with inhibition of plasma ACE. The effects of ACE inhibitors on local tissue renin-angiotensin systems (vascular in particular) may be the crucial determinant of response to treatment. Newer ACE inhibitors, such as quinapril, have favorable side effect profiles as well as apparent tissue specificity for the vascular renin-angiotensin system (and possibly other relevant cardiovascular tissue). Differentiation among ACE inhibitors should play an even more important role in the future for individualization of therapy. PMID- 1312297 TI - New techniques. Definitive answers to old questions about the pathology of non small cell carcinoma of the lung? PMID- 1312298 TI - Warthin-Finkeldey polykaryocytes demonstrate a T-cell immunophenotype. AB - Warthin-Finkeldey polykaryocytes have been described in various benign and malignant lymphoid conditions since their initial identification in tonsils of patients in the prodromal stage of measles. However, the nature of these multinucleated giant cells is obscure. The authors studied the immunohistochemical profile of the Warthin-Finkeldey-type giant cells in three cases of lymphoid proliferations (two reactive, one neoplastic) containing many multinucleated cells using a panel of paraffin-reactive antibodies. Warthin Finkeldey polykaryocytes demonstrated reactivity with Leu22 (CD43), anti-CD3, and OPD4, indicating that these cells are multinucleated T lymphocytes. The significance of these results with respect to the disorders in which these cells are found and their possible role in pathogenesis of disease are discussed. PMID- 1312299 TI - Differing prevalence of human papillomavirus RNA in penile dysplasias and carcinomas may reflect differing etiologies. AB - Penile intraepithelial neoplasias grade 3 (PIN 3) and penile carcinomas were examined for the presence of human papillomavirus (HPV) RNA transcripts by in situ hybridization using 125I-labeled RNA probes. Human papillomavirus transcripts were detected in all 10 PIN 3 lesions not associated with invasive malignant conditions but were present in only 29% of penile carcinomas (9 of 26 squamous cell carcinomas and none of 5 verrucous carcinomas). Human papillomavirus RNA-positive penile cancers were significantly more likely to exhibit adjacent PIN 3 lesions than were HPV-negative tumors, and PIN 3 lesions adjacent to tumors always contained the same HPV-RNA type as was present in the invasive tumor. The development of most penile cancers may be unrelated to HPV infection. Future epidemiologic studies of the role of sexually transmitted factors in the development of penile carcinoma should distinguish between HPV positive and HPV-negative penile cancers. PMID- 1312300 TI - Parenteral and sexual transmission of human immunodeficiency virus in intravenous drug users: a study of seroconversion. The Northern Italian Seronegative Drug Addicts (NISDA) Study. AB - To evaluate the role of parenteral and sexual transmission of human immunodeficiency virus, we studied seronegative intravenous drug users recruited from 25 drug dependence treatment centers in northern Italy. All attending intravenous drug users were asked for their consent and screened for antibodies to human immunodeficiency virus; those who were seronegative were enrolled, interviewed about their habits, and invited to follow-up visits. Between 1987 and 1989, 1,195 seronegative intravenous drug users were enrolled, 635 were followed up (mean duration, 11.9 months), and 35 seroconversions were observed. The incidence rate ratios were 3.3 (95% confidence interval (CI) 1.4-7.5) for subjects aged less than 20 years, 2.4 (95% CI 1.2-4.7) for less than 2 years of intravenous drug use, 2.2 (95% CI 0.9-5.5) for syringe sharing, and 1.0 for subjects with a sexual partner who had tested positive for human immunodeficiency virus. A case-control approach, using logistic regression and adjusting for sex, age, area, and prevalence, showed odds ratios of 13.2 (95% CI 3.1-56.8) for frequent syringe sharing and 4.0 (95% CI 1.5-10.4) for sexual contacts with seropositive partners; frequent use of condoms was associated with a reduction in risk that did not reach statistical significance. Parenteral transmission is the most important route of infection with the human immunodeficiency virus among intravenous drug users, and sexual transmission plays a relevant, additive role. PMID- 1312301 TI - Increased levels of plasma thrombomodulin in chronic myelogenous leukemia. AB - Circulating blood plasma contains proteinase-degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzyme-linked immunosorbent assay using a monoclonal antibody to protease degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 +/- 6.2 ng/ml: means +/- SD) compared with the levels in normal controls (8.0 +/- 1.9 ng/ml, n = 20) (P less than 0.001). Fibrin degradation products (D-dimer), thrombin-antithrombin III complex, and plasmin alpha 2-antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin-mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase alpha 1-proteinase inhibitor (E-alpha 1PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P less than 0.0001). The plasma levels of thrombomodulin and E-alpha 1PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti-leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E-alpha 1PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P less than 0.001). These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease-degraded fragments of it into the circulation. PMID- 1312303 TI - Application of immunocryoultramicrotomy to free cells: ultrastructural localization of myeloperoxidase in neutrophils of human peripheral blood. AB - Immunocryoultramicrotomy is generally considered the most suitable method for observing the immunostainings by monoclonal antibodies to intracellular antigens by electron microscopy. However, this procedure with the free cells such as peripheral blood cells or cultured cells is not widely used because of the difficulty in preparing ultrathin frozen sections. We report here a new technique for making ultrathin frozen sections of peripheral blood cells by positioning the cell in a semigelatinized medium for ultrasectioning. Monoclonal antibody against myeloperoxidase (MPO) was reacted with the ultrathin sections made with this new technique to observe the ultrastructural localization of intracellular MPO. MPO was observed in the primary granules of the neutrophils. PMID- 1312302 TI - Granular lymphocyte leukemia with pure red cell aplasia: usefulness of gene analysis in assessing therapeutic effect. AB - A patient with granular lymphocyte leukemia (GLL) of the CD3+, CD4-, CD8+ phenotype accompanied by pure red cell aplasia (PRCA) is described. Surface marker analysis, nonmajor histocompatibility complex (MHC)-restricted cytotoxicity assay, gene analysis, and in vitro colony assay were performed on the granular lymphocytes before and after treatment. Cyclophosphamide therapy was highly effective, and after remission clonal granular lymphocytes were no longer identified by T-cell antigen receptor (TCR) gene analysis or surface marker analysis. Lymphocytes obtained after remission did not exhibit elevated levels of non-MHC-restricted cytotoxicity, nor did they demonstrate a suppressive effect on erythroid colony formation. TCR gene analysis proved to be a sensitive parameter for evaluating the residual malignant granular lymphocytes. Gene analysis will be useful both for timing the discontinuation of treatment and for the early detection of relapse. Various factors possibly related to the development of PRCA in this patient were investigated and their significance is discussed. PMID- 1312304 TI - Human parvovirus B19 infection in hemophiliacs first infused with two high purity, virally attenuated factor VIII concentrates. AB - Human parvovirus B19 can be transmitted by coagulation factor concentrates and is highly resistant to virucidal methods. To evaluate whether the additional removal of virus by chromatographic methods during the manufacture of high-purity concentrates reduces the risk of B19 transmission, we have prospectively evaluated the rate of anti-B19 seroconversion in two groups of susceptible (anti B19 negative) hemophiliacs infused with high-purity, heated (pasteurized) or solvent-detergent-treated factor VIII concentrates. Both products infected a relatively high proportion of patients (nine of 20). PMID- 1312305 TI - Glioblastoma, transforming growth factor-beta, and Candida meningitis: a potential link. AB - The development of Candida meningitis in a patient following partial resection of a glioblastoma raised suspicion that transforming growth factor (TGF-beta), an immunosuppressive cytokine known to be produced by this tumor, would be elevated in his cerebrospinal fluid (CSF). By using a highly specific bioassay, the concentration of TGF-beta was found to be 609 pg/mL, which was 10-fold greater than the mean CSF TGF-beta value in control subjects with no neurologic disease. Increased CSF TGF-beta levels were also detected in patients with other central nervous system (CNS) diseases: malignancies and AIDS dementia complex. These findings suggest that TGF-beta may play an immunopathogenetic role in the CNS. PMID- 1312306 TI - Postmenopausal uterine bleeding due to estrogen production by gonadotropin secreting lung tumors. AB - Two postmenopausal women are described who had uterine bleeding due to hormone production by lung tumors--a large cell carcinoma in one case and a choriocarcinoma in the other. Both tumors stained positively for one or more placental peptides (human chorionic gonadotropin [hCG], placental lactogen, or pregnancy-specific beta-1 glycoprotein) and both patients had extremely elevated serum levels of hCG, suggesting the tumors had some placental-like endocrine function. Clinical and hormonal data supported the concept that the uterine bleeding resulted from estrogen excess due to steroid bio-transformation by the tumors. PMID- 1312307 TI - Insoluble immune complex-stimulated neutrophil leukotriene B4 production is dependent on Fc gamma RII and Fc gamma RIII and independent of pertussis toxin sensitive signal transduction pathways. AB - Leukotriene B4 (LTB4) release initiated by interaction of immune complexes (ICs) with Fc gamma RII and Fc gamma RIII receptors on human neutrophils was studied using well-defined complexes. Immune complexes consisting of polyclonal rabbit antibody to human albumin were prepared at equivalence (insoluble complex) and at five times antigen excess (soluble complex). Incubation of human neutrophils with soluble and insoluble ICs led to the synthesis of LTB4 from endogenous arachidonic acid (AA). LTB4 release induced by ICs was markedly inhibited by monoclonal antibodies against either Fc gamma RII or Fc gamma RIII receptor. Treatment of neutrophils with pertussis toxin significantly inhibited the release of LTB4 induced by soluble ICs. However pertussis toxin treatment minimally inhibited the LTB4 release induced by insoluble ICs. Crosslinking of either Fc gamma RII and Fc gamma RIII receptors on neutrophil surfaces induced LTB4 release. This is the first experimental observation showing that both Fc gamma RII and Fc gamma RIII directly induce neutrophil LTB4 metabolism in the absence of exogenous AA. These studies also suggest the involvement of novel pertussis toxin insensitive signal transduction pathways in insoluble ICs stimulation of neutrophils. PMID- 1312308 TI - Neutralizing antibodies against transforming growth factor beta potentiate the proliferation of Ki-1 positive lymphoma cells. Further evidence for negative autocrine regulation by transforming growth factor beta. AB - Activated lymphocytes and malignant lymphoma cells derived from them (Ki-1 positive lymphoma cells) share similar mechanisms of proliferation. To further examine the inhibitory role of endogenous transforming growth factor beta (TGF beta) in Ki-1 positive lymphoma cells, the authors studied anti-TGF beta antibodies and measured their effect on proliferation. A monoclonal antibody (T1A5) prepared against a unique antigenic epitope of high molecular weight Hodgkin's TGF beta and a polyclonal rabbit antibody prepared against highly purified 25,000 D porcine platelet TGF beta 1 were used. Both antibodies are shown here to inhibit the biological activity of Hodgkin's TGF beta and to crossreact with their respective antigens in immunoblotting. DNA synthesis by Ki 1 lymphoma cells was increased 138-fold by anti-TGF beta 1 antibody and 262-fold by anti-Hodgkin's TGF beta. Exogenous TGF beta 1 suppression was completely reversed by anti-TGF beta 1 antibody and IL-2-induced proliferation was markedly potentiated (41 fold). L-428 Reed-Sternberg cells secrete physiologically active TGF beta but have fewer than 500 TGF beta receptor sites per cell; no significant proliferative response was measured for either anti-TGF beta 1 or anti-Hodgkin's TGF beta. These results show the suppressive effect of exogenous TGF beta 1 on indolent Ki-1 lymphoma cells and suggest that the endogenous secretion of high molecular weight physiologically active TGF beta is important in maintaining the indolent nature of this low-grade Ki-1 positive lymphoma. PMID- 1312309 TI - Demonstration of cytomegalovirus nucleic acids in the coronary arteries of transplanted hearts. AB - Cytomegalovirus (CMV) infection has been associated with the development of accelerated arteriosclerosis in heart transplant recipients. This association prompted the authors to examine, using in situ hybridization techniques, the coronary arteries of 19 patients who had received heart transplants for the presence of CMV nucleic acids. Two probes were employed on formalin-fixed paraffin-embedded tissues. The first was an S35-labeled nick translated probe derived from CMV DNA. CMV nucleic acids were identified in the arterial intima of 5 (45%) of 11 transplanted hearts examined with this probe. Hybridization to cells morphologically consistent with endothelial cells, lymphocytes, and smooth muscle cells was identified. Hybridization was not detected in any of the hearts when a control probe, a vector without CMV DNA, was employed. The second probe that was used was a tritium-labeled strand-specific ribo-probe derived from the immediate early (IE1) gene of CMV. Using this second probe, hybridization was detected in the coronary arteries of three of five hearts that were positive with the DNA probe, in one of the hearts that was negative with the DNA probe, and in three (38%) of eight additional transplanted hearts. The pattern of hybridization was the same as that seen with the DNA probe, and no hybridization was detected when a control sense probe for the IE1 gene of CMV was employed. These results suggest that CMV nucleic acids are present in the coronary arteries of heart transplant recipients. PMID- 1312310 TI - HIV infection in intravenous drug users entering drug treatment, United States, 1988 to 1989. The Field Services Branch of the Centers for Disease Control. AB - BACKGROUND: Intravenous drug use has played a key role in the human immunodeficiency virus (HIV) epidemic. Standardized surveillance of HIV infection among intravenous drug users (IVDUs) is needed to determine HIV prevalence rates, to monitor changes in prevalence over time, and to describe behaviors associated with HIV infection. METHODS: In 1987, the Centers for Disease Control began collaborating with state and local health departments to conduct a national program of HIV seroprevalence surveys in a variety of populations and settings. This program includes unlinked HIV seroprevalence surveys in IVDUs entering sentinel drug treatment programs. RESULTS: From April 1988 through December 1989, annual studies were completed in 59 drug treatment centers in 33 US cities. Center-specific seroprevalence rates ranged from 0% to 48.2%, with a median of 4.6%. HIV seroprevalence rates varied widely by geographic area, with rates highest in the Northeast, intermediate in the Middle Atlantic cities of Baltimore and Washington, DC, and lower in other parts of the country. Median rates were 15.6% among African Americans, 3.2% among Hispanics, and 3.3% among Whites. CONCLUSIONS: Intravenous drug use is likely to remain an important factor in HIV transmission. This study supports the need to develop or expand programs to prevent the further introduction and spread of HIV among IVDUs and to prevent HIV transmission to their sexual partners. PMID- 1312311 TI - HIV prevalence and risk behavior among injecting drug users who participate in "low-threshold" methadone programs in Amsterdam. AB - INTRODUCTION: After the onset of the HIV epidemic, the hope arose that the "harm reduction" approach of the Amsterdam "low-threshold" methadone programs would have a function in controlling the spread of HIV among injecting drug users (IDUs). METHODS: To find evidence for this assumption, 386 IDUs participating in an HIV study between 1985 and 1989 were studied. Long-term regular participants in low-threshold methadone programs were compared with short-term and/or irregular participants. RESULTS: Controlling for possible confounders, long-term regular participants had a slightly increased but not statistically significant risk of being HIV infected. With regard to current drug use, they injected daily and shared needles as often as did short-term and/or irregular participants. CONCLUSIONS: The results suggest that the Amsterdam low-threshold methadone programs fail to diminish HIV risk behavior. If these programs want to have a positive effect on the spread of HIV, expansion of existing HIV prevention efforts, an increase in the daily methadone dose level, and measures to enforce regular attendance may be required. PMID- 1312312 TI - Implication of oxygen radicals on airway hyperresponsiveness after ovalbumin challenge in guinea pigs. AB - We elucidated the implication of oxygen radicals on airway hyperresponsiveness after ovalbumin (OA) challenge in guinea pigs. Ten days OA exposure increased airway responsiveness, i.e., a significant decrease in log [acetylcholine (Ach) PC200] (2.445 +/- 0.227) was observed compared with the control group (3.398 +/- 0.269). After OA exposure, the number of beta-adrenoceptors decreased by 38%, and adenylate cyclase activity decreased by 36% (isoproterenol stimulated) and 28% (basal). Significant increases in xanthine oxidase activities in lung tissue, bronchoalveolar lavage fluid (BALF), and serum were observed after the tenth OA exposure (49.1 +/- 11.7 mU/g tissue, 12.6 +/- 3.16 mU/ml, and 11.5 +/- 2.66 mU/ml, respectively) compared with those in the control group (7.35 +/- 6.48 mU/g tissue, 2.85 +/- 1.17 mU/ml, and 3.51 +/- 1.15 mU/ml, respectively). Administration of long-acting superoxide dismutase (SOD) (5,000 U/kg twice a day intraperitoneally) or gamma-glutamylcysteine ethyl ester (gamma-GCE) (10 mg/kg, twice a day, intraperitoneally), a prodrug of glutathione, maintained log [Ach PC200] (3.248 +/- 0.415 and 3.298 +/- 0.246, respectively) in spite of 10 days OA exposure. Decreases in the number of beta-adrenoceptors and adenylate cyclase activity were prevented by long-acting SOD or gamma-GCE. In contrast, long-acting SOD or gamma-GCE inhibited significantly, but not completely, the elevation of xanthine oxidase activities. These results support suggestions that oxygen radicals might be involved in the underlying mechanism of airway hyperresponsiveness after OA challenge in guinea pigs. PMID- 1312313 TI - Survey of cobalt exposure and respiratory health in diamond polishers. AB - This cross-sectional study was undertaken after the discovery of cobalt-related fibrosing alveolitis and bronchial asthma in diamond polishers occupationally exposed to cobalt. A total of 194 workers from 10 diamond polishing workshops and 59 workers from three other workshops from the diamond industry (control subjects) were studied; a questionnaire was administered and spirometry was performed. Cobalt exposure was assessed by environmental air sampling using both area and personal sampling and by measuring urinary cobalt concentration. When considered on a workshop basis, these environmental and biologic indices of exposure correlated well with each other. These measurements led to the definition of three cobalt exposure categories: a no exposure group, a low exposure group, and a high exposure group. The high exposure was, however, still below the present threshold limit value for cobalt (50 micrograms/m3). Spirometry showed that indices of ventilatory function (FVC and FEV1) were significantly (p less than 0.05) lower in the group with the highest exposure to cobalt. These differences were not due to differences in smoking habits. The results were confirmed when the data were analyzed by covariance analysis of lung function indices against smoking status, taking mean cobalt exposure in each workshop as a covariate, and when the data were analyzed by multiple regression analysis. This analysis showed that cobalt exposure correlated with decreased pulmonary function. Our results suggest that, during diamond polishing, exposure to cobalt at levels below the current threshold limit value is associated, on a group basis, with measurable effects on lung function parameters. The relationship between these cross-sectional epidemiologic findings and the occurrence of overt lung disease in diamond polishers remains to be established. PMID- 1312314 TI - Pneumocystis carinii pneumonia. An uncommon cause of death in African patients with acquired immunodeficiency syndrome. AB - Admissions and deaths in a pulmonary medicine ward in Abidjan, Cote d'Ivoire, West Africa, were evaluated over a 6-month period in 1989 with systematic autopsies on all patients who died. Of 473 patients admitted, 38% were HIV-1 seropositive, 4% were HIV-2 seropositive, and 14% reacted to both viruses. A total of 100 patients (21%) died, and deaths were twice as frequent in HIV seropositive compared with HIV-negative patients. The pathology of 78 autopsies showed that the predominant cause of death in HIV-seropositive patients was disseminated tuberculosis (40%). Cancer was the cause of death in 64% of HIV negative patients. Pneumocystosis was found in only 9% of HIV-seropositive autopsies. Since Pneumocystis carinii is an uncommon cause of death in this population, prophylaxis for P. carinii pneumonia is not warranted for HIV infected patients in Africa. In contrast, research on chemoprophylaxis for tuberculosis is urgently required. PMID- 1312315 TI - Effect of sympathetic nerve stimulation on lung vascular permeability in the rat. AB - The present study was undertaken to evaluate the role of sympathetic nerves in increasing lung vascular permeability. An isolated rat sympathetic nerve-lung preparation was used. Three minutes after an increase in lung weight was induced by elevating the intravascular pressure, stimulation of sympathetic nerves was performed in the presence of papaverine, which further increased the lung weight in a graded manner. After the nerve stimulation, deposits of carbon were observed in alveolar macrophages and perivascular walls, indicating an increase in vascular permeability. The response of lung weight to the sympathetic nerve stimulation was altered, depending on the magnitude of intravascular pressure change as well as on the voltage and frequency of electrical stimulation. Furthermore, these responses were prevented by tetrodotoxin. Calculation of the relationship between the maximal slope of the graded lung weight gain and the slope obtained just before the nerve stimulation gave a slope ratio at a frequency of 30 cps in normal rats of 4.47 +/- 0.21. Treatment with phentolamine diminished the value to 1.93 +/- 0.15, and with reserpine, to 1.43 +/- 0.14. In reserpinized rats, the slope ratio was restored by an administration of norepinephrine to 2.11 +/- 0.05 at 30 cps, being further increased by propranolol and blocked partially by phentolamine. The capillary filtration coefficient was not affected by either of the agents. In capsaicin-treated rats, sympathetic nerve stimulation did not cause any response in terms of lung weight (slope ratio = 1.0).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312316 TI - NHLBI workshop summary. Platelet-activating factor: role in pulmonary injury and dysfunction and blood abnormalities. PMID- 1312317 TI - Dietary supplementation with fish oil in ulcerative colitis. AB - OBJECTIVE: To determine the efficacy of fish oil supplementation in patients with active ulcerative colitis. DESIGN: Multicenter, randomized, double-blind, placebo controlled, crossover trail with 4-month treatment periods (fish oil and placebo) separated by a 1-month washout. SETTING: Four gastroenterology divisions. PATIENTS: Twenty-four patients with active ulcerative colitis entered the study. Five dropped out, and one was noncompliant. Eighteen patients completed the study. All patients had active disease as manifested by diarrhea and rectal inflammation. INTERVENTIONS: Treatment with prednisone and sulfasalazine was continued. Fish oil supplementation consisted of 18 Max-EPA (eicosapentaenoic acid) capsules daily (eicosapentaenoic acid, 3.24 g; and docosahexaenoic acid, 2.16 g). Placebo supplementation consisted of 18 identical capsules containing isocaloric amounts of vegetable oil. MEASUREMENTS: Patients were evaluated at study entry and after each diet period. Evaluations included a review of symptoms, flexible sigmoidoscopy, rectal biopsy, and rectal dialysis to measure prostaglandin E2 and leukotriene B4 levels. RESULTS: Fish oil supplementation resulted in a significant decrease in rectal dialysate levels of leukotriene B4 from 71.0 to 27.7 pg/mL (average change, -43.3 pg/mL; 95% CI, -83 to -3.6). Significant improvements were seen in acute histology index (average change, -8.5 units from a baseline of 10.5 units; CI, -12.9 to -4.2) and total histology index (average change, -8.5 units from a baseline of 14.80; CI, -13.2 to -3.8) as well as significant weight gain (average weight gain, 1.74 kg, CI, 0.94 to 2.54). No significant changes occurred in any variable during the placebo period. Seven patients received concurrent treatment with prednisone. During the fish oil supplementation period, the mean prednisone dose decreased from 12.9 mg/d to 6.1 mg/d and rose from 10.4 mg/d to 12.9 mg/d during the placebo diet period (P greater than 0.20). CONCLUSIONS: Four months of diet supplementation with fish oil in patients with inflammatory bowel disease resulted in reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain. PMID- 1312318 TI - Evaluation of DNA nuclear pattern as a prognostic determinant in resected pancreatic ductal adenocarcinoma. AB - From a cohort of 72 patients who underwent radical resection for ductal adenocarcinoma of the pancreas between 1951 and 1980, 62 paraffin-embedded specimens were analyzed by flow cytometry. Patients were divided into two groups according to the length of survival: long-term survivors (19 patients who survived 3 or more years after operation) and short-term survivors (43 patients who died within 12 months after resection). In 30 specimens (48%), the nuclear DNA pattern was diploid, whereas 32 were nondiploid (two tetraploid and 30 aneuploid). There were no significant differences in the number of diploid/nondiploid patterns, the fraction of cells in DNA synthetic (S) phase, or the DNA index between the two groups. These data suggest that there is no difference in the DNA content analysis of patients with pancreatic ductal adenocarcinoma when comparing long-term with short-term survivors following resection. PMID- 1312320 TI - An evaluation of the quinolone-theophylline interaction using the Food and Drug Administration spontaneous reporting system. AB - A review of the Food and Drug Administration's spontaneous reporting system identified 48 reports of adverse events in patients who received concomitant therapy with ciprofloxacin (n = 39) or norfloxacin (n = 9) and theophylline. The mean (SD) age of these cases was 68.4 (18.5) years; 25 patients (52%) were female. The mean percent change in theophylline concentrations was 114%, with a range of 32% to 308% following the addition of a quinolone to the patient's theophylline regimen. Fourteen (36%) of the 39 patients receiving ciprofloxacin and three (33%) of the nine patients receiving norfloxacin experienced a seizure. The accumulated evidence suggests that extreme caution should be used when quinolones are prescribed in conjunction with theophylline, particularly in elderly patients. Further research is required to identify risk factors that will more specifically predict the magnitude of the interaction. PMID- 1312319 TI - Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma. AB - Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bile ducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes +/- 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORT] with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98-months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone +/- 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent. PMID- 1312321 TI - Passive transfer of antibody to hepatitis C. PMID- 1312322 TI - Fatal acute hypernatremia caused by massive intake of salt. PMID- 1312323 TI - The opening of the inositol 1,4,5-trisphosphate-sensitive Ca2+ channel in rat cerebellum is inhibited by caffeine. AB - Ins(1,4,5)P3(InsP3)-induced Ca2+ release and [3H]InsP3 binding were measured in rat cerebellar microsomes in the presence or absence of caffeine. The quantal Ca2+ release was shown to occur in an apparently co-operative fashion with a Hill coefficient (h) of 2.2. Half-maximal Ca2+ release was observed at 900 nM-InsP3. Addition of caffeine caused changes both to the concentration of InsP3 required to cause half-maximal Ca2+ release (3.9 microM at 50 mM-caffeine) and to the apparent co-operativity (h = 1.0 at 50 mM-caffeine). Under standard conditions for [3H]InsP3 binding, caffeine had no effect, and it had no effect on InsP3 metabolism. Cyclic AMP also had no effect on the quantal release induced by InsP3. These results are consistent with the view that caffeine affects the opening (Ca2+ release) events rather than the ligand-binding events in the operation of the InsP3-sensitive Ca2+ channel. PMID- 1312324 TI - Reversible translocation of cytidylyltransferase between cytosol and endoplasmic reticulum occurs within minutes in whole cells. AB - Addition of oleic acid to Krebs II cells induced a rapid incorporation of [3H]choline into phosphatidylcholine, since 500 microM of the fatty acid stimulated choline incorporation by 5-fold over the control after 5 min of incubation. In fact, a noticeable increase in phosphatidylcholine labelling could be monitored immediately after 1 min of cell incubation with [3H]choline, at which time 50% of cytosolic cytidylyltransferase activity (EC 2.7.7.15), the regulatory enzyme of phosphatidylcholine synthesis, was translocated on to membranes. Non-esterified [3H]oleic acid content was also increased in the same range of time in the particulate fraction. Subcellular fractionation indicated that endoplasmic reticulum was the unique binding site for cytidylyltransferase even after 1 min of incubation. Also, [3H]oleic acid accumulated mainly in the same internal membrane. Addition of exogenous albumin to cells prelabelled with [3H]oleic acid induced the release of 50% of membrane-bound cytidylyltransferase activity within 1 min, together with a decrease in unesterified oleic acid in the same membrane. Although total depletion of oleic acid was obtained, total release of membrane-bound cytidylyltransferase was not. The remaining minor pool of membrane-bound cytidylyltransferase was not affected by cell incubation with dibutyryl cyclic AMP, suggesting that this pool was neither regulated by fatty acid nor modulated by cyclic-AMP-dependent protein phosphorylation. Addition of [3H]oleic acid directly to an homogenate led to a less specific accumulation of the fatty acid in the endoplasmic reticulum, but cytidylyltransferase remained exclusively associated with this membrane. We concluded that in vivo translocation of cytidylyltransferase provoked by oleic acid concerns one specific pool of the enzyme distinct from the enzyme firmly bound to endoplasmic reticulum, but other factor(s) than fatty acid seem to be required to explain the specificity of endoplasmic reticulum for cytidylyltransferase binding. PMID- 1312325 TI - Tissue-specific distribution of cross-linked somatostatin receptor proteins in the rat. AB - Pharmacological studies have suggested that the somatostatin (SS) receptor is heterogeneous and exhibits SS-14-and SS-28-selective subtypes. Whether such subtypes arise from molecular heterogeneity of the receptor protein has not been definitively established. Previous reports characterizing the molecular properties of the SS receptor by the cross-linking approach have yielded divergent size estimates ranging from 27 kDa to 200 kDa. In order to resolve this discrepancy, as well as to determine whether SS-14 and SS-28 interact with specific receptor proteins, we have cross-linked radioiodinated derivatives of [125I-Tyr11]SS-14 (T*-SS-14) and [Leu8,D-Trp22,125I-Tyr25]SS-28 (LTT*-SS-28) to membrane SS receptors in rat brain, pituitary, exocrine pancreas and adrenal cortex using a number of chemical and photoaffinity cross-linking agents. The labelled cross-linked receptor proteins were analysed by SDS/PAGE under reducing conditions followed by autoradiography. Our findings indicate that the pattern of specifically labelled cross-linked SS receptor proteins is sensitive to the concentration of chemical cross-linking agents such as disuccinimidyl suberate and dithiobis-(succinimidyl propionate). Labelled high-molecular-mass complexes of cross-linked receptor-ligand proteins were observed only when high concentrations of these cross-linkers were employed. Using optimized low concentrations of cross-linkers, however, two major labelled bands of 58 +/- 3 kDa and 27 +/- 2 kDa were detected. These two bands were identified as specifically labelled SS receptor proteins subsequent to cross-linking with a number of photoaffinity cross-linking agents as well. We demonstrate here that the 58 kDa protein is the major SS receptor protein in the rat pituitary, adrenal and exocrine pancreas, whereas the 27 kDa moiety represents the principal form in the brain. Additionally, the presence of a minor specifically labelled band of 32 kDa was detected uniquely in the brain, and a minor labelled protein of 42 kDa was observed in the pancreas. The labelling pattern obtained with LTT*-SS-28 was identical to that observed with T*-SS-14. Labelling of the 27 kDa band by either ligand was inhibited by SS-14 and SS-28 in a dose-dependent manner. Densitometric quantification showed that SS-14 exhibited greater than 2-fold greater potency than SS-28 for inhibiting the labelling of the 27 kDa species. These findings emphasize the need for careful interpretation of cross-linking data obtained for SS receptors, and provide evidence for molecular heterogeneity and for a tissue specific distribution of the two principal SS receptor proteins. PMID- 1312326 TI - Cellular and subcellular localization of enzymes of arginine metabolism in rat kidney. AB - Rat kidneys extract citrulline derived from the intestinal metabolism of glutamine and convert it stoichiometrically into arginine. This pathway constitutes the major endogenous source of arginine. We investigated the localization of enzymes of arginine synthesis, argininosuccinate synthase and lyase, and of breakdown, arginase and ornithine aminotransferase, in five regions of rat kidney, in cortical tubule fractions and in subcellular fractions of cortex. Argininosuccinate synthase and lyase were found almost exclusively in cortex. Arginase and ornithine aminotransferase were found in inner cortex and outer medulla. Since cortical tissue primarily consists of proximal convoluted and straight tubules, distal tubules and glomeruli, we prepared cortical tubule fragments by collagenase digestion of cortices and fractionated them on a Percoll gradient. Argininosuccinate synthase and lyase were found to be markedly enriched in proximal convoluted tubules, whereas less than 10% of arginase and ornithine aminotransferase, were recovered in this fraction. Arginine production from citrulline was also enriched in proximal convoluted tubules. Subcellular fractionation of kidney cortex revealed that argininosuccinate synthase and lyase are cytosolic. We therefore conclude that arginine synthesis occurs in the cytoplasm of the cells of the proximal convoluted tubule. PMID- 1312327 TI - Interactions of the ras-like protein p25rab3A with Mg2+ and guanine nucleotides. AB - The rab3A gene product is a 25 kDa guanine-nucleotide-binding protein which is expressed at high levels in neural tissue and has about 30% sequence similarity to ras. Purified p25rab3A has been used as substrate to examine its kinetics of nucleotide binding and hydrolysis, and to study the effects of Mg2+ on these processes. p25rab3A binds GDP and GTP similarly well, with nanomolar affinity. Mg2+ increases the affinity between p25rab3A and guanine nucleotides by 3- and 7 fold for GTP and GDP respectively, primarily by drastically decreasing the nucleotide off-rates. The Mg2+ binding affinity to p25rab3A. [alpha 32P]GDP was determined to be about 4 microns using entrapment of [alpha-32P]GDP as a measure of Mg2+ binding. At a Mg2+ concentration of 11 mM. GTPase activity was rate limited by the GDP off-rate. Surprisingly, at a Mg2+ concentration of 80 nM. GTPase activity was comparable with that in the presence of excess Mg2+. In this case, kcat. was rate-limiting. At Mg2+ concentrations below 10 nM there was no detectable GTPase activity, indicating that Mg2+ is required for the GTPase activity of p25rab3A. PMID- 1312328 TI - Activation of human neutrophils by mastoparan. Reorganization of the cytoskeleton, formation of phosphatidylinositol 3,4,5-trisphosphate, secretion up regulation of complement receptor type 3 and superoxide anion production are stimulated by mastoparan. AB - In human neutrophils, mastoparan induced rapid F-actin polymerization which was followed by a slow and sustained depolymerization to below the initial F-actin content. Incubation of neutrophils with pertussis toxin inhibited mastoparan stimulated actin polymerization; however it did not prevent sustained depolymerization of F-actin. Analyses of phospholipids performed in parallel revealed that mastoparan stimulated rapid formation of phosphatidylinositol 3,4,5 trisphosphate (PIP3) and consumption of phosphatidylinositol 4,5-bisphosphate (PIP2). Pertussis toxin treatment blocked mastoparan-induced formation of PIP3. Furthermore, mastoparan stimulated the release of N-acetylglucosaminidase from primary granules. Cytochalasin B enhanced mastoparan-stimulated secretion. Mastoparan triggered superoxide radical production in a cytochalasin B-sensitive manner and induced complement type 3 receptor (CR3) up-regulation. PMID- 1312329 TI - Sarcoplasmic-reticulum biogenesis in contraction-inhibited skeletal-muscle cultures. AB - We have previously shown that inhibition of the spontaneous contractile activity of cultured embryonic-chick skeletal-muscle fibres with tetrodotoxin (TTX) leads to decreased sarcoplasmic-reticulum Ca(2+)-transport rates and steady-state concentrations of the high-energy Ca(2+)-ATPase phosphoenzyme intermediate [Charuk & Holland (1983) Exp. Cell Res. 144, 143-157]. In the present study we used a monoclonal antibody to the Ca(2+)-ATPase to show that there is a decreased amount of enzyme accumulated by contraction-inhibited myotubes. Indirect immunofluorescence microscopy using the monoclonal antibody to the Ca(2+)-ATPase also revealed a disordered subcellular organization of the sarcotubular system in contraction-inhibited myotubes. The biogenesis of sarcoplasmic-reticulum proteins in TTX-paralysed myofibres was studied by labelling cells with [35S]methionine before isolation of the active Ca(2+)-pump membrane fraction. Protein turnover was selectively increased in that fraction from TTX-treated muscle cultures. Electrophoretic analysis and quantitative fluorography confirmed that decreased accumulation of the Ca(2+)-ATPase enzyme in contraction-inhibited myotubes was associated with increased turnover of this protein. The present results demonstrate that biogenesis of the sarcoplasmic-reticulum Ca(2+)-ATPase is regulated by the contractile activity of skeletal-muscle fibres. PMID- 1312330 TI - Iron-induced ascorbate oxidation in plasma as monitored by ascorbate free radical formation. No spin-trapping evidence for the hydroxyl radical in iron-overloaded plasma. AB - A study was made of the interaction of plasma ascorbate and ascorbate free radical (AFR) with exogenously added iron. The quantitative determination of AFR has the advantage that transient increases in ascorbate oxidation can be directly monitored by e.p.r. spectroscopy. An AFR signal was found in the plasma of all donors and was unaffected by superoxide dismutase, catalase and the strong iron chelator deferoxamine. These findings and the rapid decrease in AFR under a nitrogen atmosphere suggest that plasma AFR is probably a result of air auto oxidation. Iron loading of plasma did not affect the intensity of the AFR signal until the iron concentration approached or exceeded the plasma latent iron binding capacity. In iron-overloaded plasma, the intensity of the AFR signal increased to about 10 times the normal level before decreasing rapidly to undetectable levels after 15-20 min. Determination of plasma ascorbate showed that the disappearance of AFR was due to a complete loss of the vitamin. When 50 microM-ascorbate was loaded with iron in iso-osmotic phosphate buffer there was an increase in the AFR signal, independent of the iron concentration, which was stable at least for 15 min. Thus the rate of ascorbate loss in the iso-osmotic phosphate buffer was considerably lower than in iron-overloaded plasma. The addition of different iron chelators produced comparable effects on the intensity of the AFR signal in both iron-overloaded plasma and ascorbate solution. These results suggest that the characteristic behaviour of plasma AFR after iron loading is due to its specific iron-binding capacity and to plasma ferroxidase activity. The ferroxidase activity of plasma is important to promote the transfer of Fe2+ into transferrin without a transient ascorbate oxidation. Spin-trapping studies with 5,5-dimethyl-1-pyrroline N-oxide and N-t-butyl-alpha-phenylnitrone revealed that iron-overloaded plasma was unable to produce spin-trap adducts even in the presence of 50-300 microM-hydrogen peroxide or 100 microM-azide. Evidence of OH. radical formation was obtained only after the addition of EDTA. Therefore, iron-overloaded plasma itself does not produce a Fenton reaction and, if ascorbate does indeed have a free-radical-mediated pro-oxidant role, it is not detectable in plasma by spin-trapping experiments. PMID- 1312331 TI - Association of cyclic-AMP-dependent protein kinase with neurofilaments. AB - Neurofilament preparations isolated from bovine spinal cord contain cyclic-AMP dependent protein kinase (PKA) activity. Treatment of this preparation with cyclic AMP, to dissociate the regulatory subunit of the kinase from the catalytic subunit, resulted in retention of the kinase activity but loss of cyclic AMP regulation. This suggests that PKA is associated via its catalytic subunit with the neurofilament preparation. The association of exogenous PKA from bovine heart with the neurofilament preparation and with neurofilaments reconstituted from purified neurofilament proteins was also investigated. Either the free catalytic subunit or combinations of the catalytic and regulatory subunits of PKA were incubated with the preparations, and the degree of association was determined as the level of kinase activity that co-sediments with neurofilaments. The results indicate that the free catalytic subunit of PKA co-sediments with neurofilaments reconstituted from purified proteins. The regulatory subunit of PKA from bovine heart, when pre-mixed with the catalytic subunit, decreased the level of kinase that co-sediments with the neurofilament fraction in a dose-dependent manner. This effect of the regulatory subunit was reversed by inclusion of cyclic AMP in the incubation medium before centrifugation. The above findings suggest that the regulatory subunit, when attached to the catalytic subunit, has an inhibitory effect on its association with neurofilaments, with the implication that the association may be a cyclic-AMP-regulated event. PMID- 1312332 TI - Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells. AB - Synthetic lipopeptide analogues of the N-terminus of bacterial lipoprotein are effective activators of macrophages, neutrophils and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- (R) cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3Cys-Ser-(Lys)4] on tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells, using anti-phosphotyrosine antibodies. Pam3Cys-Ser-(Lys)4 concentration dependently stimulated tyrosine phosphorylation of 100/110 kDa and 60 kDa proteins and, to a lesser extent, of 55 kDa and 70/75 kDa proteins. Half-maximal and maximal effects were observed at concentrations of 1-6 and 5-50 micrograms/ml respectively. The lipopeptide-induced increase in phosphorylation was rapid and transient, with a peak response after 30-60 s. The lipopeptide (2S)-2 palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-Ser-(Lys)4 [Pam3Ahh Ser-(Lys)4] was as potent as Pam3Cys-Ser(Lys)4, whereas (2S,6S)-2-palmitoylamino 6,7-bis(palmitoyloxy)heptanoyl++ +-Ser-(Lys)4 [Pam3Adh-Ser-(Lys)4] and Pam3Cys Ser-Gly did not induce tyrosine phosphorylation. Lipopeptide-induced tyrosine phosphorylation was not affected by treatment of cells with pertussis toxin. Neither phorbol 12-myristate 13-acetate nor A23187 induced tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells. In HL-60 promyelocytes, Pam3Cys-Ser-(Lys)4 had no effect on tyrosine phosphorylation, whereas the lipopeptide also induced tyrosine phosphorylation in 1,25 dihydroxyvitamin-D3-differentiated HL-60 cells and in human neutrophils. These results show that lipopeptides are effective stimulators of tyrosine phosphorylation in mature human myeloid cells. PMID- 1312334 TI - Chromatin replication. AB - Just as the faithful replication of DNA is an essential process for the cell, chromatin structures of active and inactive genes have to be copied accurately. Under certain circumstances, however, the activity pattern has to be changed in specific ways. Although analysis of specific aspects of these complex processes, by means of model systems, has led to their further elucidation, the mechanisms of chromatin replication in vivo are still controversial and far from being understood completely. Progress has been achieved in understanding: 1. The initiation of chromatin replication, indicating that a nucleosome-free origin is necessary for the initiation of replication; 2. The segregation of the parental nucleosomes, where convincing data support the model of random distribution of the parental nucleosomes to the daughter strands; and 3. The assembly of histones on the newly synthesized strands, where growing evidence is emerging for a two step mechanism of nucleosome assembly, starting with the deposition of H3/H4 tetramers onto the DNA, followed by H2A/H2B dimers. PMID- 1312333 TI - Proteolytic processing and glycosylation of cathepsin B. The role of the primary structure of the latent precursor and of the carbohydrate moiety for cell-type specific molecular forms of the enzyme. AB - The lysosomal cysteine proteinase cathepsin B is synthesized in cultured human hepatoma HepG2 cells as an inactive 44 kDa precursor and subsequently processed to the mature single-chain enzyme with a molecular mass of 33 kDa. Intralysosomal conversion into the two-chain form results in subunits of 27 kDa, 24 kDa (heavy chain) and 5 kDa (light chain). Enzymic deglycosylation reveals that the 27 kDa polypeptide is the glycosylated variant of the carbohydrate-free 24 kDa heavy chain form. The intracellular transport to the lysosomes is dependent upon mannose 6-phosphate-containing N-linked oligosaccharides. Receptor-mediated endocytosis of human skin-fibroblast-derived procathepsin B by HepG2 cells resulted in processed molecular forms that are not distinguishable from endogenous cathepsin B, thus favouring rather a cell-type-specific processing than structural differences due to the source of the proenzyme. The conversion step of single-chain catehpsin B into the two-chain enzyme is inhibited in vivo by the irreversible cysteine-proteinase inhibitors Z-Phe-Ala-CHN2 and, albeit weaker, Z-Phe-Phe-CHN2. Both substances have no effect on the activation of procathepsin B to the mature enzyme. The carbohydrate moiety of cathepsin B exerts no significant influence on the stability and the enzymatic activity of the enzyme. PMID- 1312335 TI - Reversible histone modifications and the chromosome cell cycle. AB - During the eukaryotic cell cycle, chromosomes undergo large structural transitions and spatial rearrangements that are associated with the major cell functions of genome replication, transcription and chromosome condensation to metaphase chromosomes. Eukaryotic cells have evolved cell cycle dependent processes that modulate histone:DNA interactions in chromosomes. These are; i) acetylations of lysines; ii) phosphorylations of serines and threonines and iii) ubiquitinations of lysines. All of these reversible modifications are contained in the well-defined very basic N- and C-terminal domains of histones. Acetylations and phosphorylations markedly affect the charge densities of these domains whereas ubiquitination adds a bulky globular protein, ubiquitin, to lysines in the C-terminal tails of H2A and H2B. Histone acetylations are strictly associated with genome replication and transcription; histone H1 and H3 phosphorylations correlate with the process of chromosome condensation. The subunits of histone H1 kinase have now been shown to be cyclins and the p34CDC2 kinase product of the cell cycle control gene CDC2. It is probable that all of the processes that control chromosome structure:function relationships are also involved in the control of the cell cycle. PMID- 1312336 TI - The Tc2 transposon of Caenorhabditis elegans has the structure of a self regulated element. AB - We have analyzed the sequence of the Tc2 transposon of the nematode Caenorhabditis elegans. The Tc2 element is 2,074 bp in length and has perfect inverted terminal repeats of 24 bp. The structure of this element suggests that it may have the capacity to code for a transposase protein and/or for regulatory functions. Three large reading frames on one strand exhibit nonrandom codon usage and may represent exons. The first open coding region is preceded by a potential CAAT box, TATA box, and consensus heat shock sequence. In addition to its inverted terminal repeats, Tc2 has an unusual structural feature: subterminal degenerate direct repeats that are arranged in an irregular overlapping pattern. We have also examined the insertion sites of two Tc2 elements previously identified as the cause of restriction fragment length polymorphisms. Both insertions generated a target site duplication of 2 bp. One element had inserted inside the inverted terminal repeat of another transposon, splitting it into two unequal parts. PMID- 1312337 TI - Tissue viability. Preventing pressure sores in orthopaedics. PMID- 1312339 TI - High density lipoprotein-binding proteins in porcine liver. Isolation and histological localization. AB - The antiatherogenic properties of high density lipoproteins (HDLs) are thought to reside in their involvement in the reverse cholesterol transport pathway. Specific HDL-binding proteins could play a key role in this process. Two HDL binding proteins of approximately 90 and 180 kd were identified in porcine liver by ligand blotting and were purified to apparent homogeneity by a combination of protein extraction, DEAE-cellulose chromatography, Con A-Sepharose chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding of 125I-HDL by these proteins could be actively competed for by unlabeled HDL but not by low density lipoprotein. Polyclonal antisera have been raised against these two proteins. Each antiserum recognized only one of the HDL-binding proteins, indicating that they are not immunologically related. Moreover, striking differences in localization were observed in immunohistochemical studies. The 90-kd protein is located within the hepatocellular plates, while the 180-kd protein is present along the lining of the sinusoids. These results suggest functional differences between the two HDL binding proteins described. PMID- 1312338 TI - Oxidized low density lipoproteins stimulate phosphoinositide turnover in cultured vascular smooth muscle cells. AB - Atherogenesis is associated with alterations in the properties of different cell types, including monocytes/macrophages (foam cell formation), platelets (increased aggregation), endothelial cells (injury), and smooth muscle cells (SMCs) (lipid accumulation or foam cell formation). Oxidized low density lipoproteins (ox-LDL) play a key role in this vascular pathology. This study investigated the ability of ox-LDL to elicit chemical signaling events in cultured human vascular smooth muscle cells (VSMCs). Ox-LDL was found to stimulate phospholipase C-mediated phosphoinositide turnover in human VSMCs. This response occurred rapidly (within 1 minute) and at low concentrations of ox-LDL (half-maximal effective concentration, approximately 5 micrograms/ml). Ox-LDL stimulated inositol phosphate accumulation in human VSMCs was inhibited by pretreatment of cells with phorbol 12-myristate 13-acetate and with compounds that elevate cyclic AMP or cyclic GMP. Ca2+ antagonists also blocked the effects of ox-LDL on phosphoinositide turnover. Inhibitors of receptor-endocytotic processes (including receptor clustering, cross-linking, and cytoskeleton dependent internalization) effectively prevented ox-LDL-induced inositol phosphate generation. The data suggest that ox-LDL promotes phospholipase C mediated phosphoinositide turnover in a manner analogous to that for other Ca(2+) mobilizing hormones. The results also support an association between phosphoinositide turnover and receptor-mediated endocytosis. Prevention of the direct effects of ox-LDL on SMCs could prove an interesting therapeutic avenue for the prevention of atherosclerosis. PMID- 1312340 TI - The effect of ingestion of guar gum on ileostomy effluent. AB - Randomized, paired studies were carried out on five healthy volunteers equipped with terminal ileostomies to investigate the effect of incorporating 15 g of the viscous polysaccharide guar gum in the normal diet on the volume, weight, composition and physical properties of ileostomy effluent. Subjects ate an identical diet during two 5 d study periods, which were separated by 2 d. Outputs of fat, protein, sodium, potassium, dry weight and water were all increased during guar gum administration, but outputs of carbohydrate, calcium and phosphorus were not significantly altered. Mouth-to-stoma transit was not significantly affected and, surprisingly, the viscosity of the ileostomy effluent was reduced by guar gum. These results show that it is not always possible to predict what will happen to small intestinal function when guar gum is added to the diet from experiments carried out when guar gum is administered alone or with glucose. While our findings show that guar gum will reduce fat absorption, the mechanisms involved are more sophisticated than hitherto envisaged. PMID- 1312341 TI - Effect of fibre level, particle size and adaptation period on digestibility and rate of passage as measured at the ileum and in the faeces in the adult rabbit. AB - The use of specific methods other than gravimetric ones to analyse fibre permitted a more precise study of the degradation of cell wall (CW) in the digestive tract. Digesta flow and rate of passage measurements have not been assessed previously in rabbits to investigate fibre digestion and fibre effects simultaneously in the proximal and in the distal segments of the tract. The effect of the level of dietary fibre on ileal and overall digestibility and rate of passage were studied by comparing semi-purified diets containing only one source of CW (dehydrated lucerne (Medicago sativa) meal) given to adult female rabbits. The effect of fibre particle size and adaptation period were also investigated. Measurements of fibre composition using both colorimetric and gas liquid chromatographic techniques, showed that large amounts of (CW) were degraded in the caecocolic segments. Increasing dietary fibre level reduced the rate of passage but fibre degradation was increased, at the same time a lower digestive efficiency for energy in the small intestine was found. A small quantity of CW was apparently degraded before the caecum, assuming that the water soluble fraction of CW was essentially implicated. Grinding lucerne meal through a 1 mm instead of a 3 mm screen did not improve CW digestibility in spite of a longer rate of passage in the caeco-colic segments. Adaptation to a high-fibre diet resulted in an higher digestive volume for colon and caecum, related to an improved degradation of CW. Furthermore, digestive efficiency in the small intestine appeared higher for rabbits adapted to a high-fibre diet than that for rabbits initially fed on a low-fibre diet. PMID- 1312342 TI - Gastrointestinal morphology and absorption of monosaccharides in fowls conditioned to different types and levels of dietary fibre. AB - To test a possible influence of dietary fibre on intestinal sugar uptake, rates of absorption of 10 mM-D-[U-14C] glucose and 10 mM-D-[U-14C] xylose were measured in either jejunum or (distal) caecum, by in vivo lumen perfusion, in immature female fowls preconditioned to a standard diet containing (g/kg) either 0, 100, 200 or 400 added dried grass, 200 powdered cellulose, or 200 grass with a polysaccharidase enzyme supplement. When birds were killed after perfusion, dimensions of (unperfused) parts of their alimentary tracts were determined, and recoveries of 14C radioactivity in some body tissues were compared with measured activities absorbed. On average, absorption of glucose was 1.9 and 1.2 times faster than xylose in jejunum and caecum respectively, although these differences varied with dietary treatment and order of perfusion. Increasing grass in the diet caused significant changes in xylose absorption rate in both jejunum and caecum, but only when it was perfused before glucose. With any one sugar and intestinal segment, mean rates of absorption were correlated positively with corresponding mean rates of fluid loss from perfusate. Although their influence on sugar absorption was not well defined, the dietary fibre treatments had more pronounced effects on gross dimensions of parts of the alimentary tract and, hence, potentially on total rates of absorption. Compared with the basal diet, addition of 100, 200 or 400 g grass/kg or 200 g cellulose/kg caused significant increases in small intestine length while 200 g grass/kg with supplementary enzyme did not, and combined caecal length increased with the 400 g grass/kg and the supplementary enzyme treatments. Absorbed 14C activity was recovered in plasma after jejunal perfusions but not caecal ones, whereas it was recovered in liver and in the flushed perfused segment after both types of perfusion. Since there was overlap in absorption rates between jejunum and caecum, this result suggests that the liver may be able to distinguish and treat differently compounds absorbed in the two regions. PMID- 1312343 TI - Stoichiometry, selectivity, and exchange dynamics of lipid-protein interaction with bacteriophage M13 coat protein studied by spin label electron spin resonance. Effects of protein secondary structure. AB - Bacteriophage M13 major coat protein has been isolated with cholate and reconstituted in dimyristoyl- and dioleoylphosphatidylcholine (DMPC and DOPC, respectively) bilayers by dialysis. Fourier transform infrared spectra of DMPC/coat protein recombinants confirmed that, whereas the protein isolated by phenol extraction was predominantly in a beta-sheet conformation, the cholate isolated coat protein contained a higher proportion of the alpha-helical conformation [cf. Spruijt, R. B., Wolfs, C. J. A. M., & Hemminga, M. A. (1989) Biochemistry 28, 9158-9165]. The cholate-isolated coat protein/lipid recombinants gave different electron spin resonance (ESR) spectral line shapes of incorporated lipid spin labels, as compared with those from recombinants with the phenol extracted protein that were studied previously [Wolfs, C. J. A. M., Horvath, L. I., Marsh, D., Watts, A., & Hemminga, M. A. (1989) Biochemistry 28, 9995-10001]. Plots of the ratio of the fluid/motionally restricted components in the ESR spectra of spin-labeled phosphatidylglycerol were linear with respect to the lipid/protein ratio in the recombinants up to 20 mol/mol. The corresponding values of the relative association constants, Kr, and number of association sites, N1, on the protein were Kr approximately 1 and N1 approximately 4 for DMPC recombinants and Kr approximately 1 and N1 approximately 5 for DOPC recombinants. Simulation of the two-component lipid spin label ESR spectra with the exchange coupled Bloch equations gave values for the off-rate of the lipids leaving the protein surface of 2.0 x 10(7) s-1 at 27 degrees C in DMPC recombinants and 3.0 x 10(7) s-1 at 24 degrees C in DOPC recombinants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312344 TI - Characterization of a phagocyte cytochrome b558 91-kilodalton subunit functional domain: identification of peptide sequence and amino acids essential for activity. AB - The phagocyte NADPH oxidase is a multicomponent membrane-bound electron transport chain that catalyzes the reduction of O2 to superoxide. Cytochrome b558, the terminal electron donor to O2, is an integral membrane heterodimer containing 91- and 22-kDa subunits (gp91-phox and p22-phox, respectively). Synthetic peptides, whose amino acid sequences correspond to a gp91-phox carboxyl-terminal domain, inhibit superoxide production by blocking assembly of the oxidase from membrane and cytosol components. In this study, we examined the amino acid sequence requirements of a series of synthetic truncated gp91-phox peptides for inhibition of human neutrophil NADPH oxidase activation. RGVHFIF, corresponding to gp91-phox residues 559-565, was the minimum sequence capable of inhibiting superoxide generation. Contributions of individual amino acids to overall RGVHFIF inhibitory activity were determined by comparing the abilities of alanine-substituted RGVHFIF peptides to inhibit superoxide production. Substitution of alanine for arginine, valine, isoleucine, or either of the phenylalanines (but not glycine or histidine) within RGVHFIF resulted in loss of inhibitory activity. Synthetic gp91 phox carboxyl-terminal peptides are likely to be competitive inhibitors of the corresponding carboxyl-terminal domain of native gp91-phox by virtue of amino acid identity. We conclude that properties of arginine valine, isoleucine, and phenylalanine side chains within an RGVHFIF-containing domain of gp91-phox contribute significantly to cytochrome b558-mediated activation of the oxidase. PMID- 1312345 TI - [3Fe-4S] to [4Fe-4S] cluster conversion in Escherichia coli fumarate reductase by site-directed mutagenesis. AB - Site-directed mutants of Escherichia coli fumarate reductase in which FrdB Cys204, Cys210, and Cys214 were individually replaced by Ser and in which Val207 was replaced by Cys were constructed and overexpressed in a strain of E. coli lacking a wild-type copy of fumarate reductase and succinate dehydrogenase. The consequences of these mutations on bacterial growth, enzymatic activity, and the EPR properties of the constituent iron-sulfur clusters were investigated. The FrdB Cys204Ser, Cys210Ser, and Cys214Ser mutations result in enzymes with negligible activity that have dissociated from the membrane and consequently are incapable of supporting cell growth under conditions requiring a functional fumarate reductase. EPR studies indicate that these effects are associated with loss of both the [3Fe-4S] and [4Fe-4S] clusters, centers 3 and 2, respectively. In contrast, the FrdB Val207Cys mutation results in a functional membrane-bound enzyme that is able to support growth under anaerobic and aerobic conditions. However, EPR studies indicate that the indigenous [3Fe-4S]+,0 cluster (Em = -70 mV), center 3, has been replaced by a much lower potential [4Fe-4S]2+,+ cluster (Em = -350 mV), indicating that the primary sequence of the polypeptide determines the type of clusters assembled. The results of these studies afford new insights into the role of centers 2 and 3 in mediating electron transfer from menaquinol, the residues that ligate these clusters, and the intercluster magnetic interactions in the wild-type enzyme. PMID- 1312346 TI - Cell-free translocation of recombinant p47-phox, a component of the neutrophil NADPH oxidase: effects of guanosine 5'-O-(3-thiotriphosphate), diacylglycerol, and an anionic amphiphile. AB - We reported previously that diacylglycerol (diC8) and GTP gamma S synergize with an anionic amphiphile such as sodium dodecyl sulfate (SDS) to produce high rates of superoxide generation in a cell-free system consisting of neutrophil plasma membrane plus cytosol [Burnham, D. N., Uhlinger, D. J., & Lambeth, J. D. (1990) J. Biol. Chem. 265, 17550-17559]. Here we investigate the effects of these activating factors on the plasma membrane association in an in vitro translated radiolabeled recombinant p47-phox protein. Apparent translocation, assayed by cosedimentation with plasma membranes, required the presence of excess cytosol and an anionic amphiphile, was enhanced by both GTP gamma S and diC8, and was inhibited by high salt, correlating qualitatively with activation; up to 70% cosedimentation was observed with the combination of activators (compared with less than 20% in their absence). Similar results were obtained using heat inactivated cytosol, wherein another oxidase component, p67-phox, has been inactivated. Unexpectedly, from 50 to 80% of the apparent translocation occurred in the absence of membranes, indicating that protein aggregation accounted for a significant part of the observed translocation. Nevertheless, the percent translocation was increased in all cases by the presence of membranes, indicating some degree of protein-membrane interaction. While a control in vitro translated protein failed to translocate, cosedimentation of p47-phox occurred equally well when red blood cell or neutrophil plasma membranes lacking cytochrome b558 were used. Also, the peptide RGVHFIF, which is contained within the C-terminus of the large subunit of cytochrome b558, failed to inhibit translocation/aggregation of p47-phox, despite its ability to inhibit cell-free activation of the oxidase. The data are consistent with the following: (a) SDS, diC8, and GTP gamma S all act on cytosolic components to alter protein-protein and/or protein-membrane associations, and these changes are necessary (but not sufficient) for activation; (b) these altered associations are likely to function by increasing the local concentration of p47-phox and other components at the plasma membrane; (c) a high background of nonspecific associations in the cell-free activation system is likely to obscure any specific, functionally relevant associations (e.g., with cytochrome b558); and (d) the mechanism of translocation in the cell free system differs from that seen in intact neutrophils. PMID- 1312347 TI - Reaction of ferrous cytochrome c peroxidase with dioxygen: site-directed mutagenesis provides evidence for rapid reduction of dioxygen by intramolecular electron transfer from the compound I radical site. AB - The reaction of dioxygen with the ferrous forms of the cloned cytochrome c peroxidase [CCP(MI)] and mutants of CCP(MI) prepared by site-directed mutagenesis was studied by photolysis of the respective ferrous-CO complexes in the presence of dioxygen. Reaction of ferrous CCP(MI) with dioxygen transiently formed a FeII O2 complex (bimolecular rate constant = (3.8 +/- 0.3) x 10(4) M-1 s-1 at pH 6.0; 23 degrees C) that reacted further (first-order rate constant = 4 +/- 1 s-1) to form a product with an absorption spectrum and an EPR radical signal at g = 2.00 that were identical to those of compound I formed by the reaction of CCP(MI)III with peroxide. Thus, the product of the reaction of CCP(MI)II with dioxygen retained three of the four oxidizing equivalents of dioxygen. Gel electrophoresis of the CCP(MI)II + dioxygen reaction products showed that covalent dimeric and trimeric forms of CCP(MI) were produced by the reaction of CCP(MI)II with dioxygen. Photolysis of the CCP(MI)II-CO complex in the presence of ferrous cytochrome c prevented the appearance of the cross-linked forms and resulted in the oxidation of 3 mol of cytochrome c/mol of CCP(MI)II-CO added. The results provide evidence that reaction of CCP(MI)II with dioxygen causes transient oxidation of the enzyme by 1 equiv above the normal compound I oxidation state. Mutations that eliminate the broad EPR signal at g = 2.00 characteristic of the compound I radical also prevented the rapid oxidation of the ferrous enzyme by dioxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312348 TI - Heat shock alters the composition of heteromeric steroid receptor complexes and enhances receptor activity in vivo. AB - Under normal cellular conditions, human progesterone receptors (PR), immune isolated from cytosols of T47D breast cancer cells, associate with two heat shock proteins (hsps), hsp 90 and hsp 70. Receptors activated by hormone binding in vivo and extracted from nuclei with 0.5 M NaCl no longer associate with hsp 90 but retain association with hsp 70. We have examined the effect of heat shock treatment of cells on hsp-receptor interactions and on receptor function. Heat shock resulted in a partial reduction in cellular levels of PR, but receptors that remained were functional for both steroid and DNA binding activities. By steady-state [35S]methionine labeling prior to heat shock treatment, it was determined that heat shock did not affect the composition or maintenance of preexisting cytosolic PR.hsp 90.hsp 70 complexes. By contrast, immune isolation of PR complexes from cells pulse-labeled with [35S]methionine showed that heat shock altered the composition of newly synthesized hsps associated with PR. After heat shock, both the highly inducible form of hsp 70 (72K hsp) and a 100K hsp were bound to cytosol PR, and inducible 72K hsp remained bound with the nuclear activated PR. Neither of these hsps were associated in detectable amounts with PR under normal cellular conditions. With respect to receptor function, heat shock treatment substantially enhanced the activity of PR in vivo as determined by measuring hormone-dependent PR-mediated transcription of a target reporter gene (MMTV-CAT) that was stably transfected into T47D cells. Heat shock treatment alone, in the absence of hormone, did not stimulate MMTV-CAT expression nor did it affect transcription from a control reporter gene, pSV2-CAT, suggesting that enhanced receptor activity was due to an effect on PR-mediated processes and not to a general effect on transcription. Induction of the heat shock response by a related chemical stress (sodium arsenite) also enhanced PR activity in vivo. Interestingly, sodium arsenite produced both a greater induction of hsp 90 and hsp 70 synthesis and a greater fold enhancement of PR-mediated gene transcription than did heat shock. This suggests that enhancement of PR activity is related not only to induction of hsp synthesis but also to the severity of the stress response. The present results provide an indication that in certain cells there may exist an interrelationship between the activation pathways by which cells respond to stress and to steroid hormones. Possible mechanisms responsible for heat shock effects on PR activity are discussed. PMID- 1312349 TI - Analysis of topoisomerase I and II cleavage sites on the Drosophila actin and Hsp70 heat shock genes. AB - We have compared topoisomerase I and II cleavage sites on the actin 5C and 57A genes and the hsp70 genes in Drosophila Kc cells using the inhibitors camptothecin (topoisomerase I specific) and VM-26 (topoisomerase II specific) to assess the role of these enzymes in transcriptional regulation. Topoisomerase I cleavage sites were localized to the transcribed regions of the actin 5C and hsp70 genes and were present only when these genes were active. The actin 57A gene, shown previously to be inactive in Kc cells, had no detectable topoisomerase I cleavage sites. In contrast to topoisomerase I, topoisomerase II cleavage sites could be detected on transcriptionally active and inactive actin and hsp70 DNA sequences. Topoisomerase II cleavage sites on the inactive hsp70 gene were primarily localized to the very 5' end of the transcribed region of the gene. However, upon heat-induced activation of hsp70 transcription, topoisomerase II cleavage rapidly shifted from the 5' to the 3' end of the gene. Then, during the shutdown of hsp70 expression, there was a gradual reappearance of topoisomerase II cleavage at the 5' end of the gene that temporally correlated with the repression of hsp70 transcription. There was a similar preferential association of topoisomerase II with the 5' ends of transcriptionally repressed actin 5C and 57A genes. These results demonstrate that there are marked differences in how topoisomerases I and II interact with transcriptionally active and inactive regions of chromatin. In addition, we have identified an unusual type of topoisomerase II binding site that is preferentially associated with the 5' ends of inactive hsp70 and actin genes, suggesting that this enzyme may facilitate changes in chromatin structure that are associated with repression of gene transcription. PMID- 1312350 TI - Chemical modification of prostaglandin H synthase with diethyl pyrocarbonate. AB - The role of histidine in catalysis by prostaglandin H synthase has been investigated using chemical modification with diethyl pyrocarbonate (DEPC), an agent that has been found to rather selectively derivatize histidine residues in proteins under mild conditions. Incubation of the synthase apoprotein with DEPC at pH 7.2 resulted in a progressive loss of the capacity for both cyclooxygenase and peroxidase catalytic activities. The kinetics of inactivation of the cyclooxygenase activity were dependent on the concentration of DEPC; a second order rate constant of 680 M-1 min-1 was estimated for reaction of the apoenzyme at pH 7.2 and 0 degrees C. The kinetics of inactivation of the cyclooxygenase by DEPC exhibited a sigmoidal dependence on the pH, indicating that deprotonation of a group with a pKa of 6.3 was required for inactivation. The presence of the heme prosthetic group slowed, but did not prevent, inactivation by DEPC. The stoichiometry of histidine modification of apoenzyme during inactivation determined from absorbance increases at 242 nm agreed well with the overall stoichiometry of derivatized residues determined with [14C]DEPC, indicating that modification by DEPC was quite selective for histidine residues on the synthase. Although modification of several histidine residues by DEPC was observed, only one of the histidine residues was essential for cyclooxygenase activity. Modification of the holoenzyme with DEPC altered the EPR signal of the hydroperoxide-induced tyrosyl free radical from the wide doublet (35 G, peak-to trough) found with the native synthase to a narrower singlet (28 G, peak-to trough) quite like that found in the indomethacin-synthase complex. Reaction of the indomethacin-synthase complex with DEPC was found to increase the cyclooxygenase velocity by 9 times its initial value, to about one-third of the uninhibited value, without displacement of the indomethacin; the peroxidase was significantly inactivated under the same conditions. Histidyl residues in the synthase are thus likely to have important roles not only in cyclooxygenase and peroxidase catalysis but also in the interaction of the synthase with indomethacin. PMID- 1312351 TI - Transcriptional regulation of the human cholesterol 7 alpha-hydroxylase gene. AB - As an initial step toward understanding the transcriptional regulation of cholesterol 7 alpha-hydroxylase (CYP7) in man, we isolated and functionally characterized the 5'-flanking region of the human CYP7 gene. The nucleotide sequences of the first exon and 1.6 kb preceding the exon were determined and found to contain a TATA box at position -30, a modified CAAT box at position -92, three potential hepatocyte nuclear factor 3 (HNF-3) recognition sites at nucleotides -316, -288, and -255, respectively, and a modified sterol response element at position -271. DNA sequences containing 1.3 kb of the 5'-flanking region and 29 nucleotides of the first exon were linked to the chloramphenicol acetyltransferase gene and transiently transfected into several cell lines. Promoter activity was very strong in the human hepatoma cell line HepG2 but absent in cells of nonhepatic origin. Mutational analysis of the promoter identified several regions that function in the transcriptional regulation of CYP7. Introduction of a fragment containing the region from -432 to -220 upstream of a heterologous promoter, in either orientation, resulted in a tremendous stimulation of activity in HepG2 cells. DNase I footprint analysis identified three regions within this fragment which were protected from digestion. The overexpression of HNF-3 in HepG2 cells resulted in a 4-fold stimulation of CYP7 transcriptional activity. We suggest that the region between -432 and -220 functions as a cell-specific enhancer whose activity is controlled, in part, by HNF-3. PMID- 1312352 TI - How do organic solvents affect peroxidase structure and function? AB - The effect of organic solvents on horseradish peroxidase structure and function has been studied. Some, but not complete, enzyme denaturation occurs even in low volumes of water-miscible organic solvents (e.g., greater than 30% v/v dioxane, greater than 50% v/v methanol, and greater than 20% v/v acetonitrile) as determined by the decreased difference between the fluorescence of peroxidase's sole tryptophan residue and free L-tryptophan in solution. Absorbance and electron paramagnetic resonance spectroscopies indicate exposure of peroxidase's active site to the organic solvent. This reduces the local polarity in the enzyme's active site and results in stronger hydrogen bonding of phenolic substrates to the enzyme. In extreme cases (e.g., 95% v/v dioxane, 90% v/v acetonitrile, and ethyl and butyl acetate containing 2 and 1% v/v aqueous buffer, respectively), the transition state of the enzymic reaction is sufficiently perturbed so as to alter the magnitude of the Hammett rho value. This is most likely the result of the increased strength of hydrogen bonding between electron donating alkoxyphenols (negative sigma values) and an electrophilic group in the enzyme's active site, thereby reducing catalytic efficiencies for such substrates relative to alkyl- and chlorophenols. Perhaps the most important effect of the organic solvent, however, is the significant ground-state stabilization of phenolic substrates in organic media as opposed to aqueous buffer. This stabilization can account for nearly 4 orders of magnitude in reduction of catalytic efficiency and is manifested in increased Km's. This study indicates that enzymes can maintain much of their native active-site structure in organic media and that the effect of solvent on substrate thermodynamics must be considered. PMID- 1312353 TI - Characterization of an improved reaction center preparation from the photosynthetic green sulfur bacterium Chlorobium containing the FeS centers FA and FB and a bound cytochrome subunit. AB - A photosynthetic reaction center complex was prepared from the green sulfur bacterium Chlorobium by solubilization of chlorosome-depleted membranes with lauryl maltoside, followed by anion-exchange chromatography and molecular sieve chromatography. The purified complex was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis, optical spectroscopy, and EPR spectroscopy. The major bands migrated at apparent molecular masses of 50, 42, and 32 kDa (heme staining) and additional weaker bands at 22, 15, and 12 kDa. The isolated reaction center complex contained about 40 bacteriochlorophyll alpha molecules per primary electron donor, P840, assayed by photooxidation. It was competent in stable low-temperature photoreduction of the FeS centers FA and FB. The spectra of these acceptors and their low-temperature photochemistry in the purified complex were the same as found in intact Chlorobium membranes and similar to what had been described for photosystem I from plants. Membrane-bound cytochrome c553 copurified with the reaction center complex. A ratio of about four hemes per P840 was determined. This result indicates that cytochrome c553 that is closely associated with the reaction center is a tetraheme cytochrome, as described for some purple bacteria. PMID- 1312355 TI - Popliteal pterygium syndrome with special consideration of the cleft malformation: case report. AB - This report describes a new case of popliteal pterygium syndrome (PPS) and also a treatment protocol. The patient presented with the complete complex of PPS and additional abnormalities that have not been described in the literature: a sinus of the upper lip, an extreme hypopoplastic prolabium with aplasia of the vestibule in this area, and a velar pterygium. PMID- 1312354 TI - Bovine serum amine oxidase: half-site reactivity with phenylhydrazine, semicarbazide, and aromatic hydrazides. AB - Aromatic hydrazides of the general formula NH2NHCO(CH2)nC6H4R were covalently bound by bovine serum amine oxidase (BSAO), giving rise to optical and CD absorptions at 350-400 nm. Benzohydrazides (n = 0) reacted slowly, in the ratio of one per dimeric protein molecule, like semicarbazide. Phenylacetohydrazides (n = 1) and phenylpropionic hydrazides (n = 2) reacted instead in the ratio of two per dimer, one molecule at a much faster rate than the other. The fast reaction correlated with the loss of enzymatic activity. The contribution to the optical absorbance of either molecule was identical, but only the first one produced a CD band, the wavelength and sign of which were determined by the number n of methylene groups in the hydrazide. In n = 1 and n = 2 compounds, the reaction was faster as the R substituent became more hydrophobic (triazolyl less than imidazolyl less than phenyl), suggesting a specific interaction with the protein matrix. Phenylhydrazine was found to react with the native enzyme in the ratio of only one per protein dimer. However, one phenylhydrazine was also slowly bound by most 1:1 enzyme-hydrazide adducts, with the formation of ternary derivatives. Phenylhydrazine formed the usual intense band at 447 nm with n = 1 and n = 2 hydrazide-BSAO adducts and a weaker, blue-shifted band with the adducts of semicarbazide and of some n = 0 hydrazides. In both cases, the hydrazide absorption band was unaffected. Competition was observed with other benzohydrazides and with the second molecule of n = 1 compounds. A half-site mechanism appears to be operative, the second site being always less reactive than the first. Reactivity and adduct conformation were also affected by N,N diethyldithiocarbamate, a powerful enzyme inhibitor that binds copper. PMID- 1312356 TI - The sodium channel activator Brevetoxin-3 uncovers a multiplicity of different open states of the cardiac sodium channel. AB - The interaction of Brevetoxin 3 (Pbtx-3), a sodium channel activator, with the cardiac sodium channel was studied at the single channel level. It was found that Pbtx-3 (20 microM) shifted steady-state activation to negative potentials, without major effects on the time course of macroscopic activation or macroscopic currents decay, as calculated from averaged single-channel records. Single channel open times were found to be prolonged. Under the influence of the toxin, sodium channel openings could be observed frequently even at maintained depolarisation. These openings occurred to at least nine different subconductance levels of the open state with smaller conductivities than the maximal one and differed in their open times. Current amplitudes of these open substates were found to cluster around certain amplitude values. Appearance of substates at maintained depolarisation was dependent on the transmembrane potential (Em): Substates with smaller conductivity appeared more frequently at lower Em values whereas at higher Em values substates with higher conductivity values dominated. Furthermore, it was demonstrated that appearance of substates did not result from incomplete recovery from inactivation. From these observations it was concluded that the open substates observed correspond to different conformational states of the channel's activation gates. Under physiological conditions, when the sodium channel opens directly from its closed state these 'incomplete'-open states of the cardiac sodium channel are obscured by fast gating transitions between the corresponding, electrically silent, preopen states. Thus, Pbtx-3 acts mainly via stabilisation of the channel's preopen and different open states. A classification of sodium channel modifiers, based on their interaction with different conformational states of the channel is suggested. PMID- 1312357 TI - Effects of the antithrombitic agent PCA 4230 on agonist-induced Ca2+ entry and Ca2+ release in human platelets. AB - We have studied the effects of the antithrombitic agent PCA 4230 on the entry of Mn2+, used here as a Ca2+ surrogate for Ca2+ channels, and on the release of Ca2+ from the intracellular stores in stimulated human platelets loaded with fura-2. PCA 4230 prevented receptor-operated calcium entry activated by thrombin, ADP and collagen with no modification of the Ca2+ release from the intracellular stores. PCA 4230 also inhibited cytochrome P-450-mediated O-dealkylase activity with the same concentration-dependence as the thrombin-induced Mn2+ entry. These results suggest that the inhibitory effects of PCA 4230 on Ca2+ influx may be due to its interaction with cytochrome P-450, which has been proposed recently to be involved in the activation of receptor-operated Ca2+ channels. In addition, PCA 4230 inhibited both PAF-induced Ca2+ entry and Ca2+ release, behaving as a PAF antagonist. All these effects contribute to explain the antithrombitic action of PCA 4230. PMID- 1312358 TI - The application of pH-sensitive spin labels to studies of surface potential and polarity of phospholipid membranes and proteins. AB - The effects of pH titration on the EPR spectra of imidazolidine nitroxides located at the surface of mixed bilayers composed of dimyristoylphosphatidylglycerol (DMPG) and dimyristoylphosphatidylcholine (DMPC), and at the surface of the protein, human serum albumin (HSA), have been investigated. It is found that the shift in pKa of the amino group of the imidazolidine radical from its value of 4.6 in water depends both on the interfacial polarity (delta pKapol) and on the electrostatic surface potential (delta pKael) when it is positioned at the bilayer/water interface by an anchoring hydrocarbon tail. The polarity shift is determined to be: delta pKapol = -1.3 units at the surface of DMPC bilayers at 17 degrees C, corresponding to an effective interfacial dielectric constant of epsilon approximately 37, and depends on the temperature with a coefficient of d delta pKapol/dT approximately 0.01 per degree. The electrostatic shift at the surface of DMPG bilayers is delta pKael = +1.6 units in 0.1 M KCl, which corresponds to an electrostatic surface potential of -95 mV. This electrostatic shift depends strongly both on ionic strength and on the fraction of charged lipid in the DMPC/DMPG mixtures, in a manner that agrees with the predictions of electrostatic double-layer theory. It is found that the shift in pKa of an imidazolidine radical covalently bound at the surface of HSA is determined mainly by the surface electrostatics (delta pKapol approximately 0) and corresponds to an electrostatic potential of +33 mV in 0.01 M KCl at a pH below the isoelectric point of the protein. PMID- 1312359 TI - Purification and characterization of a protein inhibitor of the 20S proteasome (macropain). AB - An inhibitory protein for the 20S proteasome (also known as macropain, the multicatalytic proteinase complex and 20S proteinase) has been purified from bovine red blood cells. The inhibitor has an apparent molecular weight of 31,000 on SDS-PAGE and appears to form multimers under nondenaturing conditions. This protein inhibited all three of the putatively distinct catalytic activities of proteasome A (the active form of the proteinase) characterized by the hydrolysis of synthetic peptides such as Z-VLR-MNA, Z-GGL-AMC or Suc-LLVY-AMC and Z-LLE-beta NA. The inhibitor also prevented the hydrolysis of large protein substrates such as casein, lysozyme and bovine serum albumin. Proteasome L (the latent form of the proteinase) does not degrade these large protein substrates, but does hydrolyze the three synthetic peptides at rates similar to those by proteasome A. The inhibitor inhibited only two of these peptidase activities of proteasome L (hydrolysis of Z-GGL-AMC and of Z-LLE-beta NA or Suc-LLVY-AMC); it had no effect on the hydrolysis of Z-VLR-MNA. The inhibitor was specific for inhibition of the proteasome and had no effect on the activity of any other proteinase tested including trypsin, chymotrypsin, papain, subtilisin and both isoforms of calpain. Kinetic analysis indicates that the inhibitor interacted with the proteasome by a mechanism involving tight-binding. Because the proteasome appears to be a key component of the ATP/ubiquitin-dependent pathway of intracellular protein degradation, the inhibitor may represent an important regulatory protein of this pathway. PMID- 1312360 TI - Unimpaired formation of hormone-stimulated inositol trisphosphate in human mesangial cells under hyperglycemic conditions. AB - The relationship between bulk cellular myo-inositol content and phosphatidylinositol metabolism was evaluated in a human mesangial cell line under euglycemic and hyperglycemic conditions. Mesangial cells maintained in high glucose medium displayed a concentration-dependent fall in myo-inositol as measured by gas-liquid chromatography. Measurements of phosphatidylinositol, phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate mass revealed slight but statistically insignificant increases in cells exposed to high glucose containing medium. CDP-diacylglycerol: myo-inositol 3 phosphatidylinositol transferase activity, measured in plasma membranes from mesangial cells grown under control and hyperglycemic conditions, was kinetically similar with Michaelis constants (Km values) for myo-inositol of 2.9 and 2.1 mM, respectively. Finally, hormone-stimulated intracellular calcium mobilization and myo-inositol 1,4,5-trisphosphate mass was measured from mesangial cells grown under normal and hyperglycemic conditions. Both intracellular calcium and inositol trisphosphate formation were unchanged in cells previously exposed to high glucose conditions (400 mg/dl) compared to cells grown under normal glucose concentration (100 mg/dl). These data indicate that bulk changes in myo-inositol induced by hyperglycemia are neither associated with alterations in basal levels of inositol containing glycerolipids nor with changes in hormone-stimulated calcium mobilization and inositol trisphosphate formation under conditions of short term changes in extracellular glucose. PMID- 1312361 TI - [The mammographic and sonographic clinical picture of cystosarcoma phyllodes]. AB - Cystosarcoma phylloides is characterized by frequent local recurrences, by questionable tumour status and by the often large size or extension. This very rare tumour is mentioned in the literature mostly as a case report. During 1974 1989 a group of 15 cases could be collected. Starting with the different pathological and anatomical features, the typical mammographic and sonographic criteria are described. The outline of the tumour is smooth and often lobulated. The solid component has echo levels lower than the surrounding breast tissue and is mostly homogeneous. Some parts may be cystic. Endotumoral calcifications are very rare. In all cases a zone of dorsal acoustic enhancement was seen. Differential diagnosis is discussed. In large breast tumours with slow and episodic growth, the tentative diagnosis cystosarcoma phylloides should be considered more often. PMID- 1312362 TI - Inhibin and inhibin alpha-chain precursors are produced by immature rat Sertoli cells in culture. AB - Stimulation of Sertoli cells from immature rats with dibutyryl cyclic (dbc) AMP resulted in a decrease in the ratio of inhibin biological (B):immunological (I) activities in vitro. To establish the basis for this decrease, culture medium from Sertoli cells stimulated with dbcAMP was fractionated by dye-affinity chromatography, reverse-phase HPLC, and preparative PAGE. Two peaks of inhibin activity were identified: a predominantly bioactive 29-kDa peak I material (B:I ratio = 5.0) and a bio-inactive, immunoactive 27-kDa peak II material (B:I ratio = 0.1). Evidence of a subunit structure was established by iodination and immunopurification using an inhibin alpha-subunit antiserum. On reduction, peak I (29-kDa) material showed bands of 19 kDa and 14 kDa, whereas peak II (27-kDa) material showed a single 20-kDa band. On the basis of HPLC retention position, molecular mass, evidence of subunit structures and their molecular masses, and inhibin in vitro bio- and immunoactivities, peak I and II materials were most likely inhibin and the alpha-subunit precursor protein pro-alpha C. Western blotting of Sertoli cell culture medium using antiserum directed against the NH2 terminal region (alpha N) of the alpha-subunit precursor also indicated the presence of 24-kDa alpha N. It is concluded that after dbcAMP stimulation, Sertoli cells produce 29-kDa inhibin and the alpha-subunit precursor proteins pro alpha C and alpha N. The production of the alpha-subunit precursor in addition to inhibin provides an explanation for the decrease in the inhibin B:I ratio following dbcAMP stimulation of Sertoli cells in culture. PMID- 1312363 TI - Differential effects of progesterone treatment on the oxytocin-induced prostaglandin F2 alpha response and the levels of endometrial oxytocin receptors in ovariectomized ewes. AB - The oxytocin-induced uterine prostaglandin (PG) F2 alpha response and the levels of endometrial oxytocin receptors were measured in ovariectomized ewes after they had been given steroid pretreatment (SP) with progesterone and estrogen to induce estrus (day of expected estrus = Day 0) and had subsequently been treated with progesterone over Days 1-12 and/or PGF2 alpha over Days 10-12 postestrus. The uterine PGF2 alpha response was measured after an i.v. injection of 10 IU oxytocin on Days 13 and 14, using the PGF2 alpha metabolite, 13,14-dihydro-15 keto-PGF2 alpha (PGFM), as an indicator for PGF2 alpha release. The levels of oxytocin receptors in the endometrium were measured on Day 14. During the treatment with progesterone, the peripheral progesterone concentrations were elevated and remained above 1.8 ng/ml until the morning of Day 14. The PGFM responses to oxytocin in untreated controls and SP controls were low on both Days 13 and 14 whereas the levels of endometrial oxytocin receptors in the same ewes were high. Treatment with progesterone either alone or in combination with PGF2 alpha significantly (p less than 0.04) increased the PGFM response on Day 14 and reduced the levels of endometrial oxytocin receptors; treatment with PGF2 alpha alone had no effect. It is concluded that progesterone promotes the PGFM response to oxytocin while simultaneously suppressing the levels of endometrial oxytocin receptors. PGF2 alpha treatment had no effect on either the uterine secretory response to oxytocin or the levels of oxytocin receptors in the endometrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312364 TI - Myometrial oxytocin receptors and prostaglandin in the parturition process in the rat. AB - Parturition in rats is associated with an abrupt and marked increase in myometrial oxytocin (OT) receptor concentrations. In this study, we investigated the role of myometrial OT receptors in the initiation and the process of parturition. We produced chronic OT receptor blockade during the last 3 days of gestation by administration of a specific OT antagonist at 100 micrograms/day and 300 micrograms/day. We also suppressed OT receptor formation by inhibiting prostaglandin synthesis with naproxen sodium at 2 mg/day and 5 mg/day. We found that chronic blockade of OT receptors inhibited the uterotonic response to OT in Day 22 and Day 23 pregnant rats in a dose-dependent manner. OT antagonist treatment did not prolong the gestation period. However, the duration of parturition, fetal mortality, and the mortality incidence were increased in rats treated with the high dose of the OT antagonist compared to controls. Naproxen sodium at both dosage levels prolonged gestation by 24 h or longer, doubled the duration of parturition, and markedly increased fetal mortality and mortality incidence. Combined OT antagonist and naproxen treatment produced adverse outcomes similar to that produced by naproxen treatment alone. Myometrial OT receptor concentrations were markedly increased in all rats immediately postpartum, ranging from 210 to 425 fmol/mg protein compared to the 50 to 100 fmol/mg found in Day 21 and Day 22 pregnant rats. Correlation analyses between OT receptor concentrations and various parameters associated with gestation and parturition showed that there was a correlation between low OT receptor concentrations and long gestation period, prolonged parturition, and high fetal mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312365 TI - Steady-state kinetics of solitary batrachotoxin-treated sodium channels. Kinetics on a bounded continuum of polymer conformations. AB - The underlying principles of the kinetics and equilibrium of a solitary sodium channel in the steady state are examined. Both the open and closed kinetics are postulated to result from round-trip excursions from a transition region that separates the openable and closed forms. Exponential behavior of the kinetics can have origins different from small-molecule systems. These differences suggest that the probability density functions (PDFs) that describe the time dependences of the open and closed forms arise from a distribution of rate constants. The distribution is likely to arise from a thermal modulation of the channel structure, and this provides a physical basis for the following three-variable equation: [formula; see text] Here, A0 is a scaling term, k is the mean rate constant, and sigma quantifies the Gaussian spread for the contributions of a range of effective rate constants. The maximum contribution is made by k, with rates faster and slower contributing less. (When sigma, the standard deviation of the spread, goes to zero, then p(f) = A0 e-kt.) The equation is applied to the single-channel steady-state probability density functions for batrachotoxin treated sodium channels (1986. Keller et al. J. Gen. Physiol. 88: 1-23). The following characteristics are found: (a) The data for both open and closed forms of the channel are fit well with the above equation, which represents a Gaussian distribution of first-order rate processes. (b) The simple relationship [formula; see text] holds for the mean effective rat constants. Or, equivalently stated, the values of P open calculated from the k values closely agree with the P open values found directly from the PDF data. (c) In agreement with the known behavior of voltage-dependent rate constants, the voltage dependences of the mean effective rate constants for the opening and closing of the channel are equal and opposite over the voltage range studied. That is, [formula; see text] "Bursts" are related to the well-known cage effect of solution chemistry. PMID- 1312367 TI - Autocrine ligand binding to cell receptors. Mathematical analysis of competition by solution "decoys". AB - Autocrine ligands have been demonstrated to regulate cell proliferation, cell adhesion, and cell migration in a number of different systems and are believed to be one of the underlying causes of malignant cell transformation. Binding of these ligands to their cellular receptors can be compromised by diffusive transport of ligand away from the secreting cell. Exogenous addition of antibodies or solution receptors capable of competing with cellular receptors for these autocrine ligands has been proposed as a means of inhibiting autocrine stimulated cell behavioral responses. Such "decoys" complicate cellular binding by offering alternative binding targets, which may also be capable of aiding or abating transport of the ligand away from the cell surface. We present a mathematical model incorporating autocrine ligand production and the presence of competing cellular and solution receptors. We elucidate effects of key system parameters including ligand diffusion rate, binding rate constants, cell density, and secretion rate on the ability of solution receptors to inhibit cellular receptor binding. Both plated and suspension cell systems are considered. An approximate analytical expression relating the key parameters to the critical concentration of solution "decoys" required for inhibition is derived and compared to the numerical calculations. We find that in order to achieve essentially complete inhibition of surface receptor binding, the concentration of decoys may need to be as much as four to eight orders of magnitude greater than the equilibrium disociation constant for ligand binding to surface receptors. PMID- 1312366 TI - Modeling ion permeation through batrachotoxin-modified Na+ channels from rat skeletal muscle with a multi-ion pore. AB - The mechanism of ion permeation through Na+ channels that have been modified by batrachotoxin (BTX) and inserted into planar bilayers has been generally described by models based on single-ion occupancy, with or without an influence of negative surface charge, depending on the tissue source. For native Na+ channels there is evidence suggestive of a multi-ion conduction mechanism. To explore the question of ion occupancy, we have reexamined permeation of Na+, Li+, and K+ through BTX-modified Na+ channels from rat skeletal muscle. Single-channel current-voltage (I-V) behavior was studied in neutral lipid bilayers in the presence of symmetrical Na+ concentrations ranging from 0.5 to 3,000 mM. The dependence of unitary current on the mole fraction of Na+ was also examined in symmetrical mixtures of Na(+)-Li+ and Na(+)-K+ at a constant total ionic strength of 206 and 2,006 mM. The dependence of unitary conductance on symmetrical Na+ concentration does not exhibit Michaelis-Menten behavior characteristic of single ion occupancy but can be simulated by an Eyring-type model with three barriers and two sites (3B2S) that includes double occupancy and ion-ion repulsion. Best fit energy barrier profiles for Na+, Li+, and K+ were obtained by nonlinear curve fitting of I-V data using the 3B2S model. The Na(+)-Li+ and Na(+)-K+ mole fraction experiments do not exhibit an anomalous mole-fraction effect. However, the 3B2S model is able to account for the biphasic dependence of unitary conductance on symmetrical [Na+] that is suggestive of multiple occupancy and the monotonic dependence of unitary current on the mole fraction of Na+ that is compatible with single or multiple occupancy. The best-fit 3B2S barrier profiles also successfully predict bi-ionic reversal potentials for Na(+)-Li+ and Na(+)-K+ in both orientations across the channel. Our experimental and modeling results reconcile the dual personality of ion permeation through Na+ channels, which can display features of single or multiple occupancy under various conditions. To a first approximation, the 3B2S model developed for this channel does not require corrections for vestibule surface charge. However, if negative surface charges of the protein do influence conduction, the conductance behavior in the limit of low [Na+] does not correspond to a Gouy-Chapman model of planar surface charge. PMID- 1312369 TI - The receptor for urokinase-type plasminogen activator is deficient on peripheral blood leukocytes in patients with paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect in bone marrow-derived cells and is clinically associated with intravascular hemolysis, hemoglobinuria, and an increased frequency of venous thrombosis. The common denominator of PNH-affected blood cells appears to be a defect in the membrane attachment of proteins normally anchored by glycosyl-phosphatidylinositol (GPI). We report here that the cellular receptor for urokinase-type plasminogen activator (u-PAR) is deficient on affected peripheral blood monocytes and granulocytes from four individuals with PNH as evidenced by chemical cross linking analysis as well as by immunofluorescence flow cytometry using a monoclonal anti-u-PAR antibody. In contrast, on normal blood monocytes and granulocytes we find significant amounts of u-PAR, which is attached to the plasma membrane by a GPI-anchor as defined by its sensitivity towards a specific phospholipase treatment. By two-color flow cytometry it was shown that deficiency of u-PAR expression paralleled that of another GPI-anchored protein. As u-PAR is involved in the initiation of pericellular proteolysis, the reduced expression of u-PAR on PNH-affected leukocytes led to an overall reduction in the capacity for plasminogen activation by cell-surface-bound urokinase. Whereas the abnormal susceptibility of PNH-affected erythrocytes to lysis by autologous complement has been related to the low expression of three GPI-anchored complement regulatory proteins on the cell surface, we now propose that lack of u-PAR expression on the surface of peripheral blood leukocytes may be causally related to the high incidence of venous thrombosis observed in PNH patients. PMID- 1312368 TI - Structural dynamics and oligomeric interactions of Na+,K(+)-ATPase as monitored using fluorescence energy transfer. AB - The oligomeric nature of the purified lamb kidney Na+,K(+)-ATPase was investigated by measuring the fluorescence energy transfer between catalytic (alpha) subunits following sequential labeling with fluorescein 5'-isothiocyanate (FITC) and erythrosin 5'-isothiocyanate (ErITC). Although these two probes had different spectral responses upon reaction with the enzyme, our studies suggest that a sizeable proportion of their binding occurs at the same ATP protectable, active site domain of alpha. Fluorescence energy transfer (FET) from donor (FITC) to acceptor (ErITC) revealed an apparent 56 A distance between the putative ATP binding sites of alpha subunits, which is consistent with (alpha beta)2 dimers rather than randomly spaced alpha beta heteromonomers. In this work, methods were introduced to eliminate the contribution of nonspecific probe labeling to FET values and to determine the most probable orientation factor (K2) for these rigidly bound fluorophores. FET measurements between anthroylouabain/ErITC, 5' iodoacetamide fluorescein (5'IAF)/ErITC, and TNP-ATP/FITC, donor/acceptor pairs were also made. Interestingly, none of these distances were affected by ligand dependent changes in enzyme conformation. These results and those from electron microscopy imaging (Ting-Beall et al. 1990. FEBS Lett. 265:121) suggest a model in which ATP binding sites of (alpha beta)2 dimers are 56 A apart, and reside 30 A from the intracellular surface of the membrane contiguous with the phosphorylation domain. PMID- 1312370 TI - T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis. AB - T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta-chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D-J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti-calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta-chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week. PMID- 1312371 TI - Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor mediated agonists. AB - The effects of hematopoietic growth factors on human monocyte superoxide (O2-) release were investigated by using purified human monocytes in suspension. Among growth factors studied, granulocyte-macrophage colony-stimulating factor (GM CSF), macrophage-CSF (M-CSF), and interleukin-3 (IL-3) primed human monocytes and enhanced O2- release stimulated by the receptor-mediated agonists, N-formyl methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate, which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of cells with 1 to 5 ng/mL (0.07 to 0.34 nmol/L) GM-CSF, 50 to 100 ng/mL (0.5 to 1.1 nmol/L) M-CSF, or 10 to 20 ng/mL (0.6 to 1.3 nmol/L) IL-3 for 10 minutes at 37 degrees C. Potency of the maximal priming effects on FMLP- or Con A-induced O2- release was GM-CSF greater than M-CSF = IL-3. The combination of the optimal concentrations of any two CSFs resulted in the effect of more potent priming agent alone. Enhancement of O2- release by GM-CSF was observed over the complete range of effective concentrations of FMLP (10(-8) to 10(-6) mol/L). The pretreatment of monocytes with granulocyte-CSF (50 ng/mL), interferon-gamma (1,000 U/mL), or IL-4 (20 ng/mL) for 10 minutes at 37 degrees C had no effect on O2- release stimulated by FMLP or Con A. These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation. PMID- 1312372 TI - Prolonged recombinant interferon-gamma therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase activity. AB - Recombinant interferon-gamma (rIFN-gamma) therapy has become an effective form of prophylaxis for patients with chronic granulomatous disease (CGD). Preliminary studies with CGD suggested that rIFN-gamma treatment enhanced phagocyte oxidase activity and increased superoxide (O2-) production. We evaluated several aspects of neutrophil NADPH oxidase activity in 19 CGD patients (representing all four known types of CGD) receiving prolonged rIFN-gamma therapy (6 to 27 months). In contrast to earlier studies, we failed to detect any improvement in neutrophil NADPH oxidase activity in 18 of the 19 CGD patients as determined by (1) intact cell O2- production (continuous assay), (2) nitroblue tetrazolium (NBT) staining, (3) cytochrome b558 spectroscopy, and (4) activity levels of cytosol and membrane oxidase components using a cell-free activation system. One patient with a variant form of X-linked CGD had a transient increase in neutrophil O2- production following 3 months of rIFN-gamma therapy. However, this was not sustained, and was not associated with any change in cytochrome b levels. In some patients, rIFN-gamma therapy was associated with the appearance of a small subset of circulating monocytes (1% to 20%) that were NBT-positive. Although the functional significance of this monocyte subpopulation needs to be determined, these results suggest that one possible mechanism by which rIFN-gamma may benefit CGD patients is by partially correcting the respiratory burst defect in a subset of monocytes. We conclude that the clinical benefit of prolonged rIFN-gamma therapy in the vast majority of CGD patients is not due to enhanced neutrophil NADPH oxidase activity. The mechanism of action of rIFN-gamma in most CGD patients remains unknown. PMID- 1312373 TI - Subcellular distribution of the Rap1A protein in human neutrophils: colocalization and cotranslocation with cytochrome b559. AB - Rap1A, a low molecular weight guanosine triphosphate-binding protein (LMWG), has been shown previously by us to be associated with purified cytochrome b from stimulated human neutrophils. In the present studies, we show that Rap1A is also associated with affinity-purified cytochrome b from unstimulated neutrophils and use specific anti-Rap1 peptide antibodies to biochemically and immunocytochemically determine the subcellular distribution of Rap1A in resting and activated human neutrophils. Analysis of the subcellular fractionation of unstimulated cells by Western blotting of isopycnic sucrose density gradient fractions with anti-Rap1 peptide antibodies indicated that Rap1A colocalized with cytochrome b in the plasma membrane as well as in the specific granule membranes and that it was translocated, along with cytochrome b, to the plasma membrane when the cells were stimulated with phorbol myristate acetate (PMA). No evidence for a cytosolic localization of Rap1A was found in our studies; however, if the cells were disrupted by sonication, rather than N2 cavitation, a fraction of the Rap1A was released from the membrane. Electron microscopy of thin sections of cryofixed, molecular-distillation dried neutrophils labeled with anti-Rap1 antibody alone or double-labeled with anti-Rap1 and anti-cytochrome b peptide antibodies confirmed our biochemical localization, and quantitation showed that more than half of the specific granule-associated Rap1A was translocated to the plasma membrane in PMA-stimulated cells. Ultrastructural analysis of neutrophils phagocytosing Staphylococcus aureus also demonstrated the translocation of Rap1A with cytochrome b. Approximately 70% of the total Rap1A labeling was associated with the phagolysosomal membrane, the site of assembly of the superoxide generating system. The colocalization and cotranslocation of Rap1A with cytochrome b in resting and activated neutrophils is consistent with a functional association of these two molecules in the intact cell and provides further evidence for a role of this LMWG in the structure or function of the neutrophil superoxide-generating system. PMID- 1312374 TI - Clinicopathologic evaluation of recurrence in early gastric cancer. AB - Five hundred ninety-two patients with early gastric cancer underwent surgical resection from 1970 to 1986 in our hospital, and 13 died from a recurrence of their disease. A careful analysis of these 13 patients suggests that carcinomas which invaded to the submucosa tend to recur more often than those confined to the mucosa. Well differentiated and papillary adenocarcinomas characterized by protruded or elevated lesions tend to recur earlier than poorly differentiated or signet-ring cell carcinomas characterized by depressed or excavated lesions. However, both types recurred from hematogenous metastases, with the liver being the most common site. Therefore, the macroscopic and histological features presently used to characterize early gastric cancer do not provide sufficient information to accurately predict which patients are at most risk for recurrence. PMID- 1312375 TI - A case of splenic vein occlusion caused by the intravenous tumor thrombus of nonfunctioning islet cell carcinoma. AB - We report herein a case of successfully treated advanced, nonfunctioning islet cell carcinoma associated with left-sided portal hypertension. The splenic vein was obstructed by a huge intravenous tumor thrombus developing from the main pancreatic tumor. Direct invasion to adjacent organs such as the spleen, colon, left kidney and stomach was also observed, although liver metastasis was not present. Radical resection was carried out with removal of these five involved organs and the patient is alive without recurrence more than 5 years after surgery. PMID- 1312376 TI - Tamoxifen retinopathy: a rare but serious complication. PMID- 1312377 TI - Duplex pulsed Doppler sonography in the differential diagnosis of hepatocellular carcinoma and other common hepatic tumours. AB - 180 previously untreated consecutive patients with liver tumours (308 lesions), including 104 hepatocellular carcinomas (148 lesions), 43 metastases (116 lesions) and 33 haemangiomas (44 lesions), were studied to determine the value of duplex sonography in the differentiation of hepatocellular carcinoma from other tumours. For lesions measuring less than or equal to 5 cm in diameter, hepatocellular carcinoma demonstrated the highest rate and haemangioma demonstrated the lowest rate of Doppler signals from within the lesions. To differentiate malignancy from haemangioma, the presence or absence of Doppler signals from these lesions were used as criteria. The specificity and positive predictive value were very high (100%, 100%), but the sensitivity, negative predictive value and accuracy were low (61.5%, 48.3%, 71.7%, respectively). With one exception, all lesions measuring less than 3 cm in diameter with detectable Doppler signals were hepatocellular carcinoma. Using these results it is possible to differentiate hepatocellular carcinoma from metastases and haemangioma with high sensitivity, specificity, positive and negative predictive value, and accuracy (80.8%, 96.4%, 95.5%, 84.4%, 88.9%, respectively, for metastases; 80.8%, 100%. 100%, 81.5%, 89.6%, respectively, for haemangioma). We conclude that Doppler signals from within a lesion in combination with its size can aid differentiation of hepatocellular carcinoma from two other kinds of common hepatic tumour. PMID- 1312378 TI - Effect of sodium butyrate on glucocorticoid-sensitive and -resistant P1798 lymphosarcoma. AB - This study aims to examine the effect of sodium butyrate on the viability and the level of glucocorticoid receptors and cells cycle progression in glucocorticoid sensitive and -resistant P1798 cells. Our results indicated that low levels of sodium butyrate had no effect on either the viability or the receptor level. However, high-level (5 mM) sodium butyrate appeared to reduce cell viability as well as the glucocorticoid receptor level. On the other hand, sodium butyrate inhibited cell cycle progression in a dose-dependent manner. This response was similar in both the glucocorticoid-sensitive and -resistant P1798 cells. Results from this study suggested that the sodium butyrate induced effect may be cell cycle related. PMID- 1312379 TI - Insulin-pen: preliminary report on its use for multiple injection regiment in insulin-dependent diabetic patients. AB - Insulin pens are pen-like devices for multiple injection of insulin. They can cut down the equipment necessary for a multidose regimen and thus make the therapy more convenient and flexible to help improve daily-life quality. It is of interest for us to known whether the average diabetic patients are motivated to achieve better metabolic control by means of insulin-pens. Seven insulin dependent diabetic patients (male: 3, female: 4, age: 21-34 years) from the Veterans General Hospital participated in the study. None of them had diabetic proliferative retinopathy or proteinuria. They are initially treated with twice daily injection of mixtures of short- and intermediate-acting insulin (run-in period, 8 weeks). A multi-dose regimen with three premeal injections of short acting insulin with insulin-pen plus one injection of long-acting insulin at bedtime was then used during the study period (12 weeks). Improved in metabolic control as assessed by HbAlc (7.6 +/- 0.9 vs 6.9 +/- 0.8%) and mean blood glucose (175.2 +/- 34 vs 152.3 +/- 28.1 mg/dl) in all patients was found. The frequency and severity of hypoglycemic episodes were not changed. In addition, all patients chose to continue multiple injection using insulin-pen, indicating a high acceptability of such device. PMID- 1312380 TI - The predictability of matched ventilation perfusion scan in pulmonary embolism. AB - In retrospect, we reviewed 17 cases of proven pulmonary emboli at Taichung VGH. These patients were then divided into two groups, the matched and the mismatched V/Q scan. Patients with lung consolidation, along with their chest films, were studied and characterized. In the matched V/Q group (5 cases), perfusion defects were comparable with lung consolidation in both size and location. In the V/Q mismatched group, perfusion defects were larger than lung consolidation (either single or multiple foci). A matched V/Q scan in patients with a pulmonary embolism, may result from lung consolidation induced by a pulmonary infarction, localized edema, or hemorrhage. A matched V/Q scan with localized lung consolidation in a suspicious case could not rule out pulmonary embolism, and further evaluation is mandatory. PMID- 1312381 TI - Construction of detubularized ileal neobladder after radical cystoprostatectomy. AB - In an attempt to improve the patient's quality of life, we performed construction of neobladder using detubularized ileum along with radical cystoprostatectomy in 3 male patients with invasive bladder cancer. The mean followup was 28.3 months (16-45 months). All 3 patients achieved continent urination through the natural urine pathway-urethra with a satisfactory urinary stream during the day, but only 2 of them could also obtain continence in the night. Urodynamic study of the ileal neobladder showed a low pressure (mean 15.3 cm water) and no involuntary pressure spikes in the neobladder. The maximal urethral closure pressure (mean 62.0 cm water) and functional profile length (mean 3.0 cm) were adequate. In addition, the maximal uroflow rate was good (mean 16.7 ml/sec). There was no reflux in any of our patients. The radionuclide renal function study revealed that the renal function was preserved after operation in all 3 patients. Neocystourethroscopy showed no tumor and no stricture at the ileourethral anastomotic site in our 3 patients. There was no complication related to the operation. No disturbances of nutrition or electrolytes were found in any patient. All 3 patients had a satisfactory quality of life after operation though one patient died of widespread metastasis 16 months after operation. In conclusion, construction of detubularized ileal neobladder may be one of the ideal surgical procedures for bladder substitution after radical cystoprostatectomy. PMID- 1312382 TI - Intestinal permeability test in systemic lupus erythematosus. AB - Using the Cr-51 labeled EDTA resorption test, intestinal permeability was measured in 23 patients with systemic lupus erythematosus and in 16 healthy volunteers. The Cr-51 EDTA intestinal permeability test was adopted from Bjarnason et al, (Gastroenterology 1983; 85:318). 87% (14/16) of the controls had an abnormal permeability test findings (more than 2.6% in 24h). No significant difference was demonstrated between the SLE patients and the controls (SLE = 3.51 +/- 1.66; controls = 4.20 +/- 1.56, P greater than 0.05). Our study indicated that Cr-51 EDTA permeability test failed to distinguish between SLE and normal groups, and that the elevated Cr-51 EDTA excretion in the controls challenged the validity of the test. PMID- 1312383 TI - [The long-term effects of cyclosporine on cultured rat mesangial cell]. AB - In recent years, cyclosporine A(CSA) had been extensively used for anti-rejection in organ transplantation. In a high dosage, acute renal failure may occur. In this study, we cultured Sprague-Dawley rat mesangial cells in sandimmune (CSA 1 microgram/ml) and cremophor (13 micrograms/ml) for 2-4 weeks respectively, as the model for a CSA treated patient. A series of experiments were done that included PGE2/cAMP syntheses, mesangial cell proliferation and contraction. The mesangial cells were stimulated with: 1 microM ANGII, 1 microM AVP, 1 microM A23187, 1U/ml IL-1, 25ng/ml PDGF, 1mM IBMX, 10 microM forskolin and 5% fetal bovine serum (FBS). Experimental results were compared between the two groups with the Wilcoxon paired test. The only significant difference was in the cell proliferation study. In conclusion, cell proliferation was inhibited by CSA (p less than 0.05), but the influences of PGE2/cAMP synthesis and cell contraction were minimal on mesangial cells that had been cultured by a CSA contained medium for a relative long period. PMID- 1312384 TI - [Tc-99m MIBI myocardial scintigraphy in evaluation of the effect of percutaneous transluminal coronary angioplasty on coronary artery stenosis]. AB - Tc-99m 2-Methoxy-Isobutyl-Isonitrile, a newly developed myocardial perfusion radiopharmaceutical for myocardial perfusion imaging, provides an accurate, noninvasive detection of coronary artery disease. The potential advantages of Tc 99m MIBI over T1-201 have been reported extensively. The purpose of this study is to evaluate the detectability of the diseased vessels and the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) on Tc-99m MIBI myocardial perfusion scan. Twenty cases of coronary artery disease were included. Single photon emission computed tomographic (SPECT) imagings were used. Forty myocardial imagings were done before and after PTCA. Twenty nine segments of perfusion defect were found preoperatively. The sensitivity and specificity for the images to detect the individual coronary arteries were 88% and 94%, respectively. After PTCA, 25 out of 29 perfusion defects (86%) resolved. Among these, 14 were transient defects (93%) and 11 were persistent defects (79%). Persistent defects on serial thallium and Tc-99m MIBI scans are commonly thought to represent fibrosis or scar. Some investigators suggest that the recovered persistent defects on thallium scan represent hypoperfusion of viable myocardium. In our study, we found that regions of persistent defects on Tc-99m MIBI scan often revert to normal-state after PTCA (79%), indicating the similar results on thallium scans. In conclusion, Tc-99m MIBI myocardial imaging is useful in detecting coronary artery disease and monitoring success of PTCA. PMID- 1312385 TI - Prenatal diagnosis of meconium peritonitis--a case report with literature review. AB - A case of meconium peritonitis that was diagnosed ultrasonographically in the second trimester is presented. Fetal ascites, intraabdominal calcification and polyhydramnios were detected on antenatal ultrasonography. Specks of calcification were also demonstrated on abdominal radiography postnatally. The obstetric and neonatal implications of meconium peritonitis are discussed with literature review. PMID- 1312386 TI - Tailgut cyst with carcinoid: a case report. AB - Tailgut cyst, an unusual presacral lesion, is lined by a variety of epithelial types including squamous, columnar, transitional and cuboidal epithelium. Disorganized fascicles of smooth muscle may be seen in the cystic wall. Tailgut cysts are usually multiloculated, and often afflict adult women. In rare cases, adenocarcinoma arises within the tailgut cyst. We present a carcinoid tumor developing from the tailgut cyst. The tumor cells grow in ribbon and festoon patterns and are positive for argyrophilic granules. Immunostains for neuron specific enolase are also positive. Ultrastructurally, dense-core, membrane bounded neurosecretory granules are present. PMID- 1312387 TI - Quantitative analysis of the coronary angiograms. AB - This was a two-step study performed to assess the validity of a computer system in the quantification of coronary arterial angiography (CAG). First, the in vitro study involved 10 aluminum tubes in different internal diameters but the same thickness which were pre-filled with 76% urograffin followed by cinefilm taking. Acquisition and digitization of the stop film was undertaken by a videocamera linking to a computer system. The internal diameters and mean gray levels of all tubes were measured to compare with the real diameters and areas. Second, the in vivo study calculated the percentage of stenosis by visual estimation, diameter measurement and gray level measurement by the computer system from 22 vessels in 13 coronary angiograms. The percentage of patency is the ratio of the diameter or gray level from stenotic region to that of normal region in the CAG. The calculated interobserver variability by visual estimation, diameter measurement and Mean gray level measurement were studied. Good correlation was found between measured diameters and true tube diameters (r = 0.99), and between gray level and tube areas (r = 0.94). The diameter measured by computer and the gray level had lower variability (4.0% and 5.7% respectively) than visual estimation (9.8%) did. Thus, the diameter and densitometric gray level measurements might have clinical implications to assess the coronary arterial stenosis from the coronary angiograms. PMID- 1312388 TI - Scrub typhus and pregnancy: a case report and literature review. AB - Scrub typhus is still prevalent on Penghu Islands. We herein report a case in a pregnant woman who had been to Yi-Lan County in Taiwan. The patient responded well to Minocycline (Minocin) therapy without complication. Her newborn baby was found not complicated with the disease. The relative literature is reviewed. PMID- 1312389 TI - [Low back pain as a presenting symptom in patients with infective endocarditis report of three cases and literature review]. AB - Infective endocarditis may have different clinical manifestations that result from involvement of different organ systems. These include heart murmur, valvular bacterial vegetation, arterial emboli induced hematuria, conjunctival petechiae, subcutaneous Janeway's spots and Osler's nodes. Musculoskeletal manifestation yields arthralgia, arthritis, low back pain and myalgia, etc. Early recognition of these manifestations can lead to earlier treatment and recovery without delay. We report three cases of infective endocarditis who first presented low back pain. Their clinical features resolved with treatment. The pathogenesis of low back pain in infective endocarditis is not well-known. However, vertebral arterial embolization, vertebral septic necrosis or immune complex deposition is elucidated. PMID- 1312390 TI - A controlled breakdown: antigen processing and the turnover of viral proteins. PMID- 1312391 TI - Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. AB - Three novel members of the Xenopus nuclear hormone receptor superfamily have been cloned. They are related to each other and similar to the group of receptors that includes those for thyroid hormones, retinoids, and vitamin D3. Their transcriptional activity is regulated by agents causing peroxisome proliferation and carcinogenesis in rodent liver. All three Xenopus receptors activate the promoter of the acyl coenzyme A oxidase gene, which encodes the key enzyme of peroxisomal fatty acid beta-oxidation, via a cognate response element that has been identified. Therefore, peroxisome proliferators may exert their hypolipidemic effects through these receptors, which stimulate the peroxisomal degradation of fatty acids. Finally, the multiplicity of these receptors suggests the existence of hitherto unknown cellular signaling pathways for xenobiotics and putative endogenous ligands. PMID- 1312392 TI - Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases. AB - Treatment of PC12 cells with nerve growth factor (NGF) induces a rapid increase in tyrosine phosphorylation of multiple cellular proteins. Expression of a dominant inhibitory Ras mutant specifically blocked NGF- and TPA-induced tyrosine phosphorylation of two proteins of approximately 42 and 44 kd. Conversely, expression of an oncogenic variant of Ras induced tyrosine phosphorylation of the same 42 and 44 kd proteins. The 44 kd protein was immunoprecipitated with an antibody directed against extracellular signal-regulated kinase 1/mitogen activated protein kinase (MAPK) and the 42 kd protein comigrated with a 42 kd MAPK, indicating that at least one and probably both Ras-regulated phosphoproteins are MAPKs. In addition, MAPK activation, as measured by in vitro phosphorylation of myelin basic protein, was also regulated by Ras. Ras was not required for NGF-induced activation of Trk or tyrosine phosphorylation of PLC gamma 1. Thus, NGF-induced tyrosine phosphorylation occurs both prior to and following Ras action, and Ras plays a critical role in the NGF- and TPA-induced tyrosine phosphorylation of MAPKs. PMID- 1312394 TI - The Mu transpositional enhancer can function in trans: requirement of the enhancer for synapsis but not strand cleavage. AB - The phage Mu transpositional enhancer has been previously shown to stimulate the initial rate of the Mu DNA strand transfer reaction by a factor of 100. We now show that the Mu enhancer can function in trans on an unlinked DNA molecule. This activity is greatly facilitated by the presence of a free DNA end proximal to the enhancer element. Function of the enhancer in trans does not alter either the requirement for donor DNA supercoiling or for the two Mu ends to be in their proper orientation on the donor plasmid. An important consequence of these findings is that we have been able to evaluate directly the step in the transposition reaction for which the enhancer is required. We show that the role of the enhancer is limited to promoting productive synapsis; efficient strand cleavage can occur in the absence of the enhancer. PMID- 1312393 TI - ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK. AB - p21c-ras plays a critical role in mediating tyrosine kinase-stimulated cell growth and differentiation. However, the pathways through which p21c-ras propagates these signals remain unknown. We report that in PC12 cells, expression of a dominant inhibitory mutant of ras, c-Ha-ras(Asn-17), antagonizes growth factor- and phorbol ester-induced activation of the erk-encoded family of MAP kinases, the 85-92 kd RSKs, and the kinase(s) responsible for hyperphosphorylation of the proto-oncogene product Raf-1. In addition, we find that expression of the activated ras oncogene is sufficient to stimulate these events. These data indicate that ras mediates nerve growth factor receptor and protein kinase C modulation of MAP kinases, RSKs, and Raf-1. PMID- 1312395 TI - Calf thymus DNA binding/bonding properties of CC-1065 and analogs as related to their biological activities and toxicities. AB - CC-1065 is a potent natural antitumor antibiotic that binds non-covalently and covalently (N-3 adenine adduct) in the minor groove of B-form DNA. Synthetic analogs of CC-1065 do not exhibit the delayed death toxicity of CC-1065 and are efficacious anticancer agents, some of them curative in murine tumor models. In an attempt to understand the different biological properties of CC-1065 and analogs, we have determined the following quantities for CC-1065, enantiomeric CC 1065, and three biologically active analogs and their enantiomers: the calf thymus DNA (CT-DNA) induced molar ellipticity of the adduct (or how rigidly the adduct is held in the right-hand conformation of the minor groove); the stability of the adduct with respect to long incubation times and to digestion by snake venom phosphodiesterase I (SVPD); the stabilizing effect on the CT-DNA helix of the covalently and non-covalently bound species with respect to thermal melting; and the CT-DNA binding/bonding (non-covalent/covalent) profiles at a low molar ratio of nucleotide to drug. The major observations from these studies are as follows: (i) molecules which show large DNA interaction parameters, stable adducts, and significant non-covalent binding exhibit delayed death toxicity; (ii) molecules which show intermediate DNA interaction parameters and stable adducts, but do not show significant non-covalent binding, do not exhibit delayed death toxicity and are biologically active; (iii) molecules which show small DNA interaction parameters and unstable DNA adducts are biologically inactive. The results suggest that a window exists in the affinity for the minor groove of DNA wherein an analog may possess the correct balance of toxicity and activity to make a useful anticancer agent. Outside of this window, the analog causes delayed deaths or has no significant biological activity. PMID- 1312396 TI - Isolation and characterization of the initial radical adduct formed from linoleic acid and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone in the presence of soybean lipoxygenase. AB - The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) was used to trap the initial radical formed from [U-14C]linoleic acid in the reaction with soybean lipoxygenase. By using low levels of enzyme and relatively short incubation times it was possible to avoid the formation of secondary oxidation products and polymers. The adduct was extracted after methyl esterification, and isolated by a combination of open column chromatography on silicic acid and high pressure liquid chromatography on Spherisorb S5 CN with non-aqueous solvents. The 1:1 POBN-linoleate adduct was characterized by UV, IR and ESR spectra of the appropriate HPLC column fraction, by the ratio of the UV absorption to 14C content, and by mass spectrometry of the reduced (hydroxylamine) form. The results indicated that POBN trapped a linoleic acid carbon-centered radical such that POBN was attached to the fatty acid chain at C-13 or C-9 (two isomers), the linoleate double bonds having become conjugated in the process. The exact locations of the bridges in the two isomers were only tentatively determined. There was no evidence for the presence of oxygen-bridged adducts. The trapped linoleoyl radical adduct provides evidence for the production of a free radical as part of the enzymatic mechanism of soybean lipoxygenase. PMID- 1312397 TI - Altered regulation of arachidonic acid metabolism by SV40 immortalized human urothelial cells. AB - Regulation of arachidonic acid metabolism was investigated in an SV40 immortalized, non-tumorigenic human urothelial cell line (SV-HUC). This cell line is being used to evaluate the multistage carcinogenic process. Media from confluent cultures were analyzed for radioimmunoassayable prostaglandin E2 (PGE2). A variety of agonists, including 12-O-tetradecanoylphorbol-13-acetate (TPA) and A23187 were tested and did not increase PGE2 synthesis within 2 h of addition. This was not due to the lack of prostaglandin H synthase activity because addition of exogenous arachidonic acid increased PGE2 synthesis. Cultures prelabeled overnight with [3H]arachidonic acid failed to increase the release of radioactivity following agonist addition. Thus, the lack of an early response in SV-HUC appears to be due to decreased release of endogenous arachidonic acid by phospholipase(s). After a 24 h incubation with 0.1 microM TPA or 1.0 microM A23187, the addition of arachidonic acid elicited significantly more PGE2 synthesis in agonist-treated cells than it did in control cells. Microsomes from 24 h TPA-treated cells produced approximately 15-fold more PGE2 than did those from control cells. In addition, the PGE2 content of overnight media was significantly greater in TPA-treated cells than in control cells. The 24 h agonist response was blocked by cycloheximide and staurosporine--inhibitors of protein synthesis and protein kinase C respectively. Pretreatment of cells with aspirin, an irreversible inhibitor of prostaglandin H synthase, prior to addition of TPA did not prevent the late 24 h TPA-mediated increase in PGE2 synthesis. Results suggest that this late effect of TPA is due to de novo synthesis of prostaglandin H synthase. Thus, SV-HUC has lost the early but retains the late response to agonists. PMID- 1312398 TI - The tumour promoters dieldrin and phenobarbital increase the frequency of c-Ha ras wild-type, but not of c-Ha-ras mutated focal liver lesions in male C3H/He mice. AB - The frequency and pattern of mutations at codon 61 of the c-Ha-ras protooncogene were analysed in glucose-6-phosphatase-deficient hepatic lesions of male C3H/He mice occurring either spontaneously or after continuous treatment with 10 p.p.m. dieldrin or 500 p.p.m. phenobarbital (PB) in their diet. At 52 weeks after start of promoter administration, enzyme-altered liver lesions had developed in 41% (15/37) of untreated control mice and in 67% (10/15) and 63% (10/16) of mice treated with dieldrin or PB respectively. The average numbers of focal lesions per mouse were 0.57 in the control, 1.5 in the dieldrin and 1.0 in the PB group. Lesions were punched out from frozen liver sections and used for mutation analysis by allele-specific oligonucleotide hybridization following in vitro amplification of DNA via polymerase chain reaction. In the control group, 12 out of 21 liver lesions (57%) showed c-Ha-ras mutations, while five out of 23 (22%) and four out of 16 (25%) lesions were mutated in the dieldrin and PB groups. Taking the different numbers of animals in the three experimental groups into account, our data indicate that the tumour promoters increased the frequency of c Ha-ras wild-type but not of c-Ha-ras mutated focal liver lesions, suggesting that the mutations had occurred spontaneously and were not related to treatment. Since c-Ha-ras mutations were found to be frequent in large but infrequent in small hepatocellular lesions, these mutations may represent in livers of C3H/He mice an endogenous promoting principle that provides a selective growth advantage to the mutated progenitor cells. PMID- 1312400 TI - Angiotensin-converting enzyme activity in cerebrospinal fluid (CSF) PMID- 1312399 TI - Upregulation of O6-alkylguanine-DNA-alkyltransferase expression and the presence of double minute chromosomes in alkylating agent selected Chinese hamster cells. AB - Chinese hamster V79 lung fibroblasts are sensitive to the toxic effects of chloroethylating agents such as mitozolomide (Mz) and express very low levels (less than 2 fmol/mg) of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (ATase). These cells were subjected to selection by treatment with serially increasing doses of Mz. After each dose, the surviving population was expanded and ATase activity was determined in cell extracts. ATase specific activity increased stepwise and in cells surviving selection at 120 micrograms/ml Mz had reached 430 fmol/mg protein: polyacrylamide gel electrophoresis and fluorography showed the size of the ATase as 25 kDa. Cytological examination of these cells showed the presence of double minute (DM) chromosomes (mean approximately 3/cell) but no obvious homogeneously staining regions. In cells grown in continuous culture without further selection no marked decrease in ATase activity or DM frequency was observed. Karyotype analysis and DNA profiling confirmed that the parent and selected cells were of the same origin with, in the latter case, the probable loss or gain of a single restriction endonuclease site. No major differences were seen in the intensity of hybridization signals following Southern analyses of DNA from control and Mz selected cells using the human ATase cDNA as a probe. These results indicate that the ATase gene is not amplified in the Mz selected cells and suggest that increased ATase activity is a consequence only of increased transcription or translation of the ATase gene. PMID- 1312401 TI - Dermoid cyst with crystalline inclusions in adjacent cortex: an ultrastructural study. AB - Dermoids are rare tumors of the central nervous system. So far, no electron microscopic studies of these tumors have been available. We describe the histology and ultrastructure of a dermoid cyst in a patient with situs inversus and discuss the relationship of keratin and aseptic meningitis, a well-known complication. Histological examination showed an epidermal matrix with 2-4 layers, a cyst containing keratin and debris, some hairs and sebaceous glands. In some areas, chronic inflammation had destroyed the matrix of the cyst wall. Gliosis of the adjacent brain parenchyma was evident, as were eosinophilic rod shaped crystals. Electron microscopy revealed gliosis with Rosenthal fibers in brain parenchyma adjacent to the tumor capsule. Intracellular osmiophilic, crystalline inclusions were prominent within this area. Glial cells and neuropil were spared. No gross intracellular pathology was seen. PMID- 1312402 TI - Granulofilamentous profiles in lower motor neurons: a sporadic case of amyotrophic lateral sclerosis with many Lewy body-like inclusions. AB - In a 62-year-old man with an 8-month course of sporadic classical amyotrophic lateral sclerosis, many Lewy body-like hyaline inclusions (LI) were observed in spinal anterior horn cells, hypoglossal nuclei, nucleus ambiguus, and motor nuclei of the trigeminal nerve. These motor neurons showed a mild degree of neuronal loss, several Bunina bodies, spheroids and chromatolytic neurons. Tract degeneration was limited to pyramidal tracts. In addition to intensely stained LI, immunoreactive skeins or granules were recognized by a polyclonal anti ubiquitin antibody. Thick filaments of 15 to 20 nm in diameters with granules formed conglomerated masses with varying amounts of neurofilaments in the anterior horns, corresponding to light microscopically observed LI. More commonly, these thick granulofilamentous profiles were dispersed in small bundles or individually in the cytoplasm. Electron microscopically, there was no close association of filaments with Bunina bodies. PMID- 1312403 TI - Immunocytochemical study of ballooned neurons in cortical degeneration with neuronal achromasia. AB - We studied the immunocytochemical characteristics of the ballooned neurons (BN) in three patients with cortical degeneration with neuronal achromasia (CDNA) using antibodies to phosphorylated neurofilaments (PNF), tau, Alz-50, ubiquitin, beta (A4) amyloid, and glial fibrillary acidic protein. All BN exhibited intense perikaryal staining for PNF protein. Most BN and some normal-appearing neurons also stained for ubiquitin and Alz-50. The BN did not immunostain for tau protein, and none of the cases had tau-reactive neocortical neurofibrillary tangles or Pick bodies. One case had occasional senile plaques that stained for beta amyloid; no case had amyloid angiopathy. Our findings suggest that the pathophysiologic basis of the cortical degeneration in CDNA involves an alteration of neuronal cytoskeletal metabolism affecting neurofilament and possibly microtubular proteins in conjunction with activation of the ubiquitin proteolytic system. PMID- 1312404 TI - Involvement of the brain stem reticular formation in familial amyotrophic lateral sclerosis. AB - The reticular formation of the brain stem of three cases of familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement showed a paucity of large neurons, chromatolytic neurons and Lewy body-like intracytoplasmic inclusions. Some of the remaining neurons were stained focally by antibodies to phosphorylated neurofilaments and ubiquitin; the staining patterns were similar to those seen in anterior horn cells. Within the reticular formation, the medial part of the medulla oblongata was most pronouncedly affected. The reticular formation should be among the systems other than motor neurons that may be involved in this type of familial ALS. PMID- 1312406 TI - Patient-controlled analgesia with fentanyl in children. AB - We have found that fentanyl delivered by PCA provides an effective alternative when adverse effects occur with other more frequently used narcotics. Although anecdotal experience exists concerning the use of fentanyl PCA in adults, dosing guidelines in children must depend on consideration of the current narcotic regimen and the use of equipotent doses of fentanyl. Our initial experience suggests that this is a safe and reliable technique; however, until prospective studies further delineate dosing guidelines, close observation (continuous pulse oximetry and hourly checks of respiratory rate) of these patients is recommended. With such caveats, fentanyl PCA appears to provide an acceptable alternative to "more conventional" narcotics. PMID- 1312405 TI - Peripheral motor-sensory neuropathy in membranous lipodystrophy (Nasu's disease): a case report. AB - A case of membranous lipodystrophy (ML) with peripheral polyneuropathy (PN) is described. A 40-year-old woman presented with dementia, multiple lytic bone lesions with typical membranous material in adipose tissues and neurophysiological and pathological findings of peripheral neuropathy. We describe the first case of ML with PN. It is interesting since nerve involvement might be an additional cause of symptoms usually attributed to bone lesions. PMID- 1312407 TI - Communications of the winter meeting of the Medical Research Society. 12-13 December 1991, London. Abstracts. PMID- 1312408 TI - Role of renal arterial pressure in the regulation of extracellular volume in conscious dogs. AB - 1. This study in conscious dogs examined the quantitative effects of a reduction in the renal arterial pressure on the renal homeostatic responses to an acute extracellular fluid volume expansion. 2. Seven female beagle dogs were chronically instrumented with two aortic catheters, one central venous catheter and a suprarenal aortic cuff, and were kept under standardized conditions on a constant high dietary sodium intake (14.5 mmol of Na+ day-1 kg-1 body weight). 3. After a 60 min control period, 0.9% (w/v) NaCl was infused at a rate of 1 ml min 1 kg-1 body weight for 60 min (infusion period). Two different protocols were applied during the infusion period: renal arterial pressure was maintained at 102 +/- 1 mmHg by means of a servo-feedback control circuit (RAP-sc, 14 experiments) or was left free (RAP-f, 14 experiments). 4. During the infusion period, in the RAP-sc protocol as well as in the RAP-f protocol, the mean arterial pressure increased by 10 mmHg, the heart rate increased by 20 beats/min, the central venous pressure increased by 4 cmH2O and the glomerular filtration rate (control 5.1 +/- 0.3 ml min-1 kg-1 body weight, mean +/- SEM) increased by 1 ml min-1 kg 1. 5. Plasma renin activity [control 0.85 +/- 0.15 (RAP-f) and 1.08 +/- 0.23 (RAP sc) pmol of angiotensin I h-1 ml-1] decreased similarly in both protocols.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312409 TI - Plasma levels of endothelin in chronic renal failure and after renal transplantation: impact on hypertension and cyclosporin A-associated nephrotoxicity. AB - 1. Plasma levels of endothelin were measured in 30 patients with chronic renal failure, 32 patients on chronic haemodialysis treatment and 25 renal graft recipients with stable renal graft function. 2. In patients with chronic renal failure as well as in patients on regular haemodialysis treatment, mean plasma levels of endothelin were significantly increased (4.59 +/- 2.09 pg/ml, 10.08 +/- 3.12 pg/ml, respectively) when compared with normal subjects (1.88 +/- 0.6 pg/ml, P less than 0.01, P less than 0.001, respectively). 3. In the group with chronic renal failure a positive correlation between the plasma level of endothelin and the plasma concentration of creatinine was observed (P less than 0.003). 4. Renal graft recipients on cyclosporin A with stable renal graft function had a normal plasma level of endothelin suggesting that cyclosporin A nephrotoxicity is not mediated by endothelin. 5. Hypertensive patients with chronic renal failure or on regular haemodialysis and hypertensive renal graft recipients did not differ from the corresponding normotensive population with regard to the plasma level of endothelin, demonstrating that an increased plasma level of endothelin does not play a major role in the pathogenesis of renal hypertension. PMID- 1312411 TI - Enhanced synthesis of neutrophil-activating peptide-1/interleukin-8 in active ulcerative colitis. AB - 1. We studied neutrophil-activating peptide-1/interleukin-8 in inflammatory bowel disease. 2. Mucosal levels of neutrophil-activating peptide-1/interleukin-8 were significantly higher in patients with active ulcerative colitis [median 74.5 (range 17.7-450.8) pg/mg] than in patients with active Crohn's disease [10.4 (4 46.9) pg/mg; P less than 0.002] or in normal control subjects [10.4 (4-16.6) pg/mg; P less than 0.002]. 3. Circulating neutrophil-activating peptide 1/interleukin-8 was generally undetectable but there were higher levels of anti neutrophil-activating peptide-1/interleukin-8 antibodies in patients with active ulcerative colitis [62.9 (3.4-239) ng/ml] than in patients with active Crohn's disease [5.9 (2.1-18.10) ng/ml; P less than 0.001] or in control subjects [6.1 (3.2-15.8) ng/ml; P less than 0.001]. 4. Neutrophil-activating peptide 1/interleukin-8 may be of specific functional importance in mediating inflammation in ulcerative colitis. PMID- 1312410 TI - Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung. AB - 1. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of ventilation perfusion matching, we looked at the interaction between hypoxic and almitrine induced vasoconstriction in isolated rat lungs perfused with blood at constant flow. Increases in pressure represented increases in resistance. 2. Almitrine, given in increasing doses between challenges with 2% O2, enhanced hypoxic vasoconstriction at low doses but attenuated it at high doses. 3. Stimulus response curves to hypoxia of increasing severity gave a sigmoid curve. 4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion. 5. Small doses of almitrine enhanced the action of mild to moderate hypoxia, medium doses attenuated moderately severe hypoxia, whereas high doses depressed vasoconstriction due to all degrees of hypoxia. 6. These effects of almitrine on hypoxic vasoconstriction were compared with the effect of solvent by analysis of variance; the results substantiated significant enhancement of hypoxia by small doses and attenuation by large doses. 7. In patients, if similar effects apply, small doses of almitrine would assist ventilation-perfusion matching, but large doses might worsen it. 8. Almitrine-induced vasoconstriction was attenuated by a fall in perfusate temperature in a similar manner to hypoxic vasoconstriction. It was also attenuated by three drugs, chlorpheniramine, propanolol and diethylcarbamazine, all of which also decrease hypoxic vasoconstriction. The similarity between hypoxic and almitrine-induced pulmonary vasoconstriction is further confirmed. PMID- 1312412 TI - Exposure of rat colonic mucosa to human semen in vivo induces mucosal cytolysis, abolishes fluid absorption and raises paracellular permeability. AB - 1. The effects of human semen on rat descending colon fluid absorption, permeability to 3H-labelled polyethylene glycol 4000 and the histological appearance of the mucosa were examined. Also, the semen was fractioned by centrifugation into plasma and sperm fractions and the effects of these fractions on rat colonic function were examined. The effects of trypsin and bacterial collagenase, mimetics of acrosin and seminal collagenase activity, were examined in order to investigate which component of human semen alters colonic permeability. 2. Contact between human semen and rat descending colonic mucosa for 3 h decreased fluid absorption from 52.0 +/- 2.9 microliters h-1 cm-2 (control) to 10.7 +/- 3.4 microliters h-1 cm-2 (P less than or equal to 0.001), increased the permeability to polyethylene glycol 4000 from 0.099 +/- 0.006 cm/h (control) to 0.31 +/- 0.04 cm/h (P less than or equal to 0.001) and caused cytolysis of the surface mucosa. 3. Spermatozoa inside the colonic lumen were destroyed within 1 h with release of acrosomal contents; this raised the activity of the acrosomal proteolytic enzyme acrosin by 40-fold (P less than or equal to 0.005) and of seminal plasma metalloproteinase (collagenase) by about twofold (mean activity 1623 +/- 240 units/ml of luminal fluid). 4. The changes in colonic permeability induced by seminal plasma were similar to those induced by similar activities of clostridial collagenase. 5. We conclude that seminal collagenase is present in sufficient amounts to cause acute damage to the colonic mucosa, and that this could be a factor in facilitating viral transmission across the colonic wall. PMID- 1312413 TI - Nitrogen absorption from isonitrogenous solutions of L-leucyl-L-leucine and L leucine: a study in the isolated perfused rat small intestine. AB - 1. We assessed the efficacy of nitrogen absorption from luminal L-leucine (1.2 and 12 mmol/l) and from isonitrogenous L-leucyl-L-leucine (0.6 and 6.0 mmol/l) in a preparation of vascularly and luminally perfused rat small intestine by measuring luminal leucyl-leucine disappearance and venous leucine appearance. 2. No intact dipeptide was found in the vascular perfusate. Leucine-nitrogen absorption, as judged by venous leucine appearance, was as efficient from free leucine (29 +/- 3 and 245 +/- 19 ng-atom min-1 g-1) as from leucyl-leucine (27 +/ 4 and 211 +/- 58 ng-atom min-1 g-1). It was not reduced in the presence of glycyl-L-proline or of the brush-border dipeptidase inhibitors alanine-beta naphthylamide and cilastatin. 3. After one passage of the whole small intestine, only trace amounts of dipeptide, but large amounts of free leucine, were detected in the luminal effluent. Peptidase activity in the luminal effluent was demonstrated in 100,000 g supernatant and was inhibited by p-hydroxy mercuribenzoate, but not by brush-border dipeptidase inhibitors. 4. We propose that nitrogen absorption from luminal leucyl-leucine may proceed predominantly via intraluminal peptide hydrolysis and subsequent transport of free leucine. Nevertheless, our findings and conclusions are at variance with previous observations and current opinion on intestinal handling of dipeptides, which may be due, in part, to the different methodological approach. PMID- 1312414 TI - Kinetics of sodium-lithium countertransport activity in patients with uncomplicated type 1 diabetes. AB - 1. Increased erythrocyte sodium-lithium countertransport activity has been reported to be associated with nephropathy in type 1 diabetes and linked to a family history of essential hypertension. 2. This study aimed to determine the mechanism of increased sodium-lithium countertransport activity. Sodium-lithium countertransport kinetics were measured in uncomplicated and hyperlipidaemic type 1 diabetic patients. 3. In the nine out of 31 uncomplicated type 1 diabetic patients who had high sodium-lithium countertransport activity, the sodium affinity (Km) was normal but the maximum velocity (Vmax) was increased. 4. Hyperlipidaemia, when present in diabetic patients, was associated with increased sodium-lithium countertransport activity, but could not explain the high activity in uncomplicated type 1 diabetic patients in whom plasma lipid concentrations were normal. 5. Sodium-lithium countertransport activity is increased in type 1 diabetes by a mechanism different to that in essential hypertension, where the mechanism is a low Km (increased sodium affinity). Hence familial hypertension cannot explain the raised sodium-lithium countertransport activity in type 1 diabetes. PMID- 1312415 TI - Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. AB - 1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes. PMID- 1312416 TI - Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes. AB - 1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.-m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01 11.90) versus 18.60 (3.20-32.60) micrograms/100 micrograms of protein, P less than 0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (LS/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean +/- SEM, 37.6 +/- 1.3 versus 33.8 +/- 0.6, P less than 0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically (LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P less than 0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes. PMID- 1312417 TI - Leg extensor power and functional performance in very old men and women. AB - 1. Residents of a chronic care hospital (13 men of mean age 88.5 +/- 6 SD years and 13 women of mean age 86.5 +/- 6 SD years) who had multiple pathologies were assessed for leg extensor capability in several ways. 2. A custom-built rig was used to assess leg extensor power, that is, maximal power output over less than 1 s in a single extension of one leg. Performance measures were obtained by timing chair rises (from a standard chair 0.43 m high), stair climbing (four risers, total height 0.635 m) and a walk (6.1 m). For each measurement the best of several trials were recorded as definitive. 3. Leg extensor power was significantly correlated with all performance measures, but the performance measures were not related to each other except for chair rising and walking speed. 4. Women had significantly less extensor power than men, but their power explained more of the variance in performance, e.g. power accounted for 86% of the variance in walking speed. 5. There was no relation within the group between age and any of the variables measured. 6. Measurement of leg extensor power in frail elderly people may prove useful in focusing effective rehabilitation programmes. PMID- 1312418 TI - Hysteresis of the venous pressure-volume relationship in the forearm of borderline hypertensive subjects. AB - 1. The forearm venous pressure-volume relationship was studied in 14 young men with borderline hypertension and in 16 control subjects of the same age and sex. Strain-gauge plethysmography was used to evaluate volume changes after slow increases and decreases in distention, in order to estimate the amplitude of the hysteresis curve. 2. Compared with normotensive control subjects, subjects with borderline hypertension had significantly higher values of blood pressure, heart rate and forearm blood flow. 3. Baseline forearm venous tone was slightly, but not significantly, increased in borderline hypertensive subjects (21.35 +/- 6.53 versus 18.75 +/- 5.95 mmHg ml-1 100 ml-1) and was significantly enhanced after a cold pressor test. The increase was no higher in the borderline hypertensive subjects than in the normotensive control subjects. 4. The area of the hysteresis curve was significantly decreased (7.58 +/- 3.58 versus 10.34 +/- 5.67 arbitrary units; P = 0.0092) as was the extent of isotonic relaxation (creep) (0.28 +/- 0.11 versus 0.39 +/- 0.22 ml/100 ml; P = 0.0098) in borderline hypertensive subjects compared with control subjects. Both parameters were unaffected by the cold pressor test. 5. The study suggests that the viscous component of the venous wall is altered in young patients with borderline hypertension, indicating intrinsic changes in vascular segments which are not exposed to increased intraluminal pressure. PMID- 1312420 TI - Vascular responses and ion exchange in diabetes. PMID- 1312419 TI - Extent of ischaemia caused by hepatic vascular exclusion as evaluated in a canine model. AB - 1. The difference in the extent of liver ischaemia between a hepatic vascular exclusion model and an inflow occlusion model were investigated by determining Indocyanine Green retention and hepatic mitochondrial redox state during 2 h of ischaemia in 10 mongrel dogs. The splanchnic venous bed and/or the infra-hepatic inferior vena cava were decompressed by pump-driven veno-venous bypass. 2. The Indocyanine Green retention test revealed that there was no hepatic blood flow in the hepatic vascular exclusion model during ischaemia (96.8 +/- 0.73% retention of the dye after 20 min), whereas hepatic blood perfusion was still present significantly in the inflow occlusion model (78.1 +/- 1.19% retention of the dye after 20 min) (P less than 0.01). 3. The mitochondrial redox potential of the liver in the dogs with hepatic vascular exclusion decreased immediately after the induction of ischaemia and remained fixed at extremely low levels. By contrast, in the dogs with inflow occlusion the redox potential decreased gradually after induction and was maintained significantly higher than that in dogs with hepatic vascular exclusion during 2 h of ischaemia (P less than 0.01). 4. It is concluded that the extent of liver ischaemia in the hepatic vascular exclusion model with pump-driven shunt is significantly different from that in the inflow occlusion model with shunt. PMID- 1312421 TI - Infection of bovine fetuses at 120 days' gestation with virulent and avirulent strains of bluetongue virus serotype 11. AB - Bluetongue virus infection in sheep and cattle during fetal development causes neuropathology. Two strains of bluetongue virus serotype 11 designated as UC-2 and UC-8 have different virulence patterns in newborn mice. These viruses have distinctly different electropherotype patterns on polyacrylamide gel electrophoresis indicating a genetic difference in these two viruses of the same serotype. Four bovine fetuses each were inoculated intramuscularly with either UC 2 or UC-8, and one fetus was inoculated with placebo. The inoculation was made intramuscularly through the uterine wall at 120 days' gestation, and the bovine fetuses were recovered by cesarean section 12 or 20 days after inoculation. Fetal blood was collected for virus isolation and serology. Virus was reisolated from brain, blood, lung and liver. Both strains, UC-2 and UC-8, cause severe lesions in the 120 day fetuses. The encephalomalacic lesions occurred earlier and were more severe in fetuses inoculated with UC-8 as compared to those inoculated with UC-2. The subtle differences observed in the fetuses inoculated with the two different strains suggest that there is a difference in pathogenic potential of the two viruses. These differences do not appear to be completely dependent upon the host species. PMID- 1312422 TI - Investigations of environmental conditions during cluster indicate probable vectors of unknown exogenous agent(s) of multiple sclerosis. AB - During the tail-end of an active cluster several environmental investigations indicated that wildbirds were very probably the vectors of the unknown exogenous agent of MS. Canine distemper and genetic-autoimmune theories were very definitely eliminated because of the unusual pattern of the cluster. Studies of several avian pathogens unveiled Marek's (MDV) and/or IBD (Gumboro) as the most likely candidates for exogenous agent of MS. PMID- 1312423 TI - Cholecystokinin-octapeptide stimulates hypothalamic-pituitary-adrenal function in rats: role of corticotropin-releasing hormone. AB - Peripherally-administered cholecystokinin (CCK) is a profound suppressor of food intake, can promote anxiety, and causes the acute release of ACTH into plasma. Centrally administered corticotropin-releasing hormone (CRH), on the other hand, not only represents the principal stimulus to the pituitary corticotroph cell, but also has been shown to suppress appetite and to be profoundly anxiogenic. Because of the overlap in the effects of peripherally administered CCK and of centrally administered CRH, we report here a study to determine whether sulphated CCK octapeptide (CCK-8) could induce the release of CRH within the central nervous system. To accomplish this task, we first assessed the dose-related effects of CCK-8 on ACTH release. Graded doses of CCK-8 (0.1-10 micrograms/kg BW) given in an i.v. bolus to freely moving male rats, resulted in a dose-dependent increase of plasma immunoreactive (IR)-ACTH (ED50: 1-10 micrograms/kg BW). The lowest maximal stimulatory dose of CCK-8 (5 micrograms/kg BW) was used in all subsequent experiments. To evaluate whether CCK-induced ACTH secretion was mediated by a peripheral CCK receptor, an i.v. bolus injection of vehicle or L 364,718 (1 mg/kg BW), a specific, highly potent peripheral CCK receptor antagonist, was given before the i.v. administration of CCK-8 or vehicle. Plasma IR-ACTH response to CCK-8 was significantly attenuated by L-364,718. A role for the vagal afferents that contain CCK receptors in peripherally administered CCK mediated hypothalamic-pituitary-adrenal (HPA) axis activation was examined in animals that had been pretreated with capsaicin, a potent neurotoxin that destroys vagal afferents. Plasma IR-ACTH and IR-corticosterone responses in capsaicin-treated animals were significantly lower than those in vehicle treated rats. In subsequent in vivo experiments, pituitary stalk-transected and sham operated animals were used to evaluate whether CCK-8 stimulates the HPA axis via a centrally mediated mechanism. IR-ACTH and IR-corticosterone responses to i.v. CCK-8 were significantly reduced in the pituitary stalk-transected compared to sham-operated animals. In further effort to determine whether the central nervous system was involved in the plasma IR-ACTH response to the peripheral administration of i.v. CCK-8, we compared the effects of the i.v. administration of CRH antisera vs. normal rabbit serum on this parameter. IR-ACTH and IR corticosterone responses to i.v. CCK-8 were significantly reduced in the context of pretreatment with CRH antisera compared to the administration of normal rabbit serum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1312424 TI - Chronic activation of the hypothalamo-pituitary-adrenal axis and loss of circadian rhythm during adjuvant-induced arthritis in the rat. AB - Adjuvant-induced arthritis (AA) in Sprague-Dawley rats resulted in a chronic increase in plasma levels of ACTH and corticosterone (B). Joint inflammation became clinically apparent between days 12-15 after injection of adjuvant and reached a peak on day 21, after which time it subsided. In AA animals, plasma ACTH and B levels in the morning (0800-0900 h) on days 7, 8, 9, and 21 were significantly higher than those in control animals (day 0). The corresponding evening ACTH and B levels in AA animals were not significantly different from evening levels in the control animals. Adrenal weight in AA animals was increased on day 21, while thymic weight diminished gradually from days 7-21 postinjection. Development of AA was associated with activation of the hypothalamo-pituitary adrenal axis, with increased morning ACTH and B levels and abolition of normal diurnal ACTH and B rhythms. This model of chronic inflammatory stress clearly activates the ACTH drive despite increased corticosteroid feedback in the morning, resulting overall in chronically increased B secretion. PMID- 1312425 TI - Regulation of corticotropin-releasing factor secretion from Leydig cells by serotonin. AB - CRF is produced in the Leydig cells and acts as a negative autocrine regulator of Leydig cell function. To clarify the hormonal control of CRF secretion by Leydig cells, we evaluated the participation of serotonin (5HT) and serotonin agonists in the release of CRF from Leydig cells and their effects on hCG-induced cAMP generation and steroidogenesis. Serotonin stimulated CRF secretion up to 4-fold above basal levels and inhibited basal and hCG-stimulated cAMP generation and testosterone production (ID50, 1 nM). The inhibitory action of 5HT was prevented by a CRF antibody and the alpha-helical CRF-(9-41) antagonist. The selective 5HT2 receptor agonist (+-)1-[2,5-dimethoxy-4-iodophyryl]2-amino propane hydrochloride (DOI) also stimulated CRF secretion and inhibited hCG-stimulated cAMP generation and testosterone production to control levels (ID50, 7 microM). Serotonergic 5HT1A, 5HT1B/1C, 5HT1D, and 5HT3/5HT2 agonists were less effective inhibitors of hCG-stimulated cAMP and testosterone production, while agonists for the 5HT3 receptor had no effect. [125I]DOI binding studies in Leydig cells demonstrated two sets of receptors with Kd values in the nanomolar and micromolar range, with low and high capacities, respectively. The low affinity site differed from that of brain receptors (Kd, 4.2 nM) and displayed higher binding capacity (50-fold). The selective 5HT2 receptor antagonist ketanserin prevented CRF stimulation and blocked the inhibitory actions of 5HT and DOI, while the alpha 1-adrenergic antagonist prazosin had no effect. Also, treatment of cells with ketanserin increased sensitivity to hCG and raised maximal cAMP and testosterone production. 5HT was a more effective stimulus than hCG in stimulating CRF secretion, and gonadotropin-induced CRF release was inhibited by ketanserin. Inhibitory effects of exogenous CRF were demonstrable after blockade of 5HT action by ketanserin. The inhibitory actions of 5HT were unaffected by pertussis and cholera toxins and were reversed by the addition of 8-bromo-cAMP. These results demonstrate that 5HT acts on 5HT2 receptors in Leydig cells that are distinct from those in the brain to stimulate CRF secretion through a pertussis toxin-insensitive G-protein. This action of 5HT is predominantly mediated by the low affinity 5HT2-binding site and requires full occupancy for maximal CRF stimulation, indicating the absence of spare receptors. 5HT-stimulated CRF inhibits basal and hCG-induced cAMP generation and steroidogenesis. Furthermore, 5HT mediates the stimulatory action of LH/hCG on CRF secretion from Leydig cells and, thus, participates in a negative autoregulatory loop to limit the testosterone response to the gonadotropic stimulus. PMID- 1312426 TI - Morphology of adenohypophysial tumors in mice transgenic for vasopressin-SV40 hybrid oncogene. AB - Transgenic mice for the promoter sequence of bovine arginine vasopressin (AVP) gene fused to large SV40 T-antigen coding sequence develop pituitary tumors and insulin-producing pancreatic tumors. In order to establish the cellular composition of the pituitary tumors, histological, immunocytochemical, in situ hybridization, and electron microscopic technics were applied. Pituitary anterior lobe tumors were identified in 10 out of 14 glands examined. In 2 of these cases, intermediate lobe tumors were also found. The anterior lobe tumors contained a variable number of GH immunoreactive cells. In situ hybridization performed in 7 cases revealed a diffuse distribution of GH messenger RNA over all tumor cells. Ultrastructurally, the tumors contained undifferentiated cells with very small secretory granules and rare cells showing some resemblance to somatotrophs. The results indicate that these pituitary tumors are composed of undifferentiated somatotrophs. The presence of a few PRL immunoreactive cells in four tumors and scattered TSH immunoreactive cells in two tumors supports the view that somatotrophs have the potential to produce PRL and TSH. The intermediate lobe tumors were immunoreactive for ACTH and intensely positive for POMC mRNA. In the nontumorous adenohypophyses, no hyperplasia of any cell type was noted. Several GH immunoreactive cells exhibited pleomorphic, giant nuclei and mitoses. In conclusion, the majority of transgenic mice for AVP/large T-antigen develop pituitary tumors originating in and composed of somatotrophs. Less frequently, intermediary lobe tumors were present as well. AVP/SV40 transgenic mice provide a unique experimental model for somatotroph tumors that are neither preceded by, nor associated with somatotroph hyperplasia. PMID- 1312427 TI - Growth of the endometrial adenocarcinoma cell line AN3 CA is modulated by tumor necrosis factor and its receptor is up-regulated by estrogen in vitro. AB - We demonstrate that tumor necrosis factor (TNF) has a biphasic effect on the growth of the human endometrial adenocarcinoma cell line AN3 CA in vitro. Low levels (0.2-5 pg/ml) of TNF were moderately growth stimulatory (up to 20% enhancement), while levels over 100 pg were growth inhibitory (up to 45% inhibition). Northern blot analysis showed expression of the 75-kilodalton (kDa) TNF receptor mRNA, but no expression of the 55-kDa TNF receptor mRNA or TNF mRNA. The growth of these cells was not directly affected by physiological concentrations (10(-7)-10(-9) M) of 17 beta-estradiol (E2). However, [125I]TNF binding studies and Scatchard analysis showed that 18-h coculture with 10(-8) M E2 increased the number of TNF receptors expressed on these cells 3-fold. Quantitative mRNA analysis confirmed that 75-kDa TNF receptor mRNA expression increased within 4 h of incubation with E2. These observations suggest an interaction between the endocrine and the immune systems, with an important implication for the homeostasis of endometrial tissues. PMID- 1312428 TI - Mechanism of regulation of thyrotropin-releasing hormone receptor messenger ribonucleic acid in stably transfected rat pituitary cells. AB - We showed previously that the level of TRH receptor (TRH-R) mRNA in rat pituitary GH3 cells is down-regulated by TRH. Here, we study the mechanism of regulation of TRH-R mRNA in a line of GH3 cells that are stably transfected with mouse pituitary TRH-R cDNA (GH-mTRHR-1 cells). GH-mTRHR-1 cells were found to have 2.4 times the number of TRH-Rs and to stimulate a 2.5-fold greater increase in inositol phosphates in response to TRH than the parent cell line and to show TRH induced down-regulation of TRH-R number. GH-mTRHR-1 cells contained 26 +/- 1.6 molecules of mouse TRH-R mRNA/cell and 230 +/- 31 molecules of mRNA for the neomycin resistance gene (NEO) with which it was cotransfected. In GH-mTRHR-1 cells, TRH caused a dose-dependent transient decrease in mouse TRH-R mRNA, with a nadir to 20% of control levels after 6 h. In contrast, TRH did not affect NEO mRNA or glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA, an endogenous gene product. TRH stimulated the rate of transcription of mouse TRH-R DNA by approximately 2-fold, but did not affect total poly(A) RNA synthesis. Most importantly, TRH caused a 4-fold increase in the rate of degradation of mouse TRH R mRNA, but did not affect degradation of GAPDH mRNA. The half-lives of mouse TRH R and GAPDH mRNAs were 3 and more than 20 h in control cells and 0.75 and more than 20 h in cells treated with 1 microM TRH for 1.5 h, respectively. These data show that the predominant effect of TRH on mouse TRH-R mRNA in GH-mTRHR-1 cells is to enhance the rate of its degradation. We suggest, therefore, that down regulation of TRH-R mRNA caused by TRH in the parent GH3 cell line is secondary to increased TRH-R mRNA degradation. PMID- 1312429 TI - Distinct tissue distribution and cellular localization of two messenger ribonucleic acids encoding different subtypes of rat endothelin receptors. AB - Endothelins (ETs) are very potent vasoconstrictive peptides and have diverse functions in both vascular and nonvascular tissues. This investigation concerns the tissue distribution and cellular localization of rat mRNAs encoding two different subtypes of ET receptors (ETA and ETB). We isolated 46 cDNA clones from a rat lung cDNA library by hybridization with the bovine ETA cDNA. The characterization of these cDNA clones indicated that they represent either the ETA or ETB cDNA. In situ and blot hybridization analyses revealed that the rat ETA mRNA is predominantly expressed in vascular smooth muscle cells of a variety of tissues, bronchial smooth muscle cells, myocardium, and the pituitary gland. There is no significant expression of ETB mRNA in vascular smooth muscle cells, and ETA, thus, plays a primary role in ET-induced vascular contraction. ETB mRNA is more widely distributed in various cell types of many tissues. Its prominent expression is seen in glial cells throughout the brain regions, epithelial cells of the choroid plexus, ependymal cells lining the ventricle, myocardium, endothelial cells of glomeruli, and epithelial cells of the thin segments of Henle's loops. Our investigation demonstrates that the mRNAs for the two subtypes of rat ET receptors show specialized expression patterns of cell types in both brain and peripheral tissues. PMID- 1312430 TI - Acute intravenous corticotropin-releasing factor administration: effects on insulin secretion in lean and genetically obese fa/fa rats. AB - The effect of an i.v. administration of different doses (250, 500, and 1000 pmol) of ovine CRF (oCRF) on plasma glucose and insulin levels in lean and genetically obese fa/fa rats was investigated. In both phenotypes, i.v. CRF promoted a rapid (peak at 1 min) transient doubling of basal insulin levels without a concomitant change in glycemia. The dose-dependency of this early insulin response was bell shaped in both lean and obese animals, with a maximal response at 500 pmol oCRF. After this early rise in insulinemia, glycemia increased in a dose-dependent manner in both lean and obese rats. It was accompanied by a bell-shaped insulin response in lean rats, while such a response was linear in obese rats. The early transient stimulatory effect of CRF on plasma insulin levels could not be prevented by the prior administration of an anti-CRF serum or the alpha-helical CRF-(9-41) antagonist, although administration of either one of these compounds was effective in preventing the CRF-induced changes in the pituitary-adrenal axis. The effect of CRF on the early insulin response was, however, completely suppressed by an acute cholinergic blockade (i.v. injection of atropine). It is suggested that i.v. CRF administration mimics the reflex, cephalic phase insulin secretion. Such cephalic phase insulin output is known to play a role in oral glucose tolerance and may be of physiopathological importance in the Zucker rat strain. PMID- 1312431 TI - Hypothalamic-pituitary-adrenal axis function in the Zucker obese rat. AB - The development of many endocrine, metabolic, and behavioral abnormalities characteristic of genetically obese Zucker rats is dependent upon the presence of glucocorticoids, the secretion of which is regulated by a neuroendocrine cascade initiated by hypothalamic release of CRF. Recent reports have inferred alterations in central CRF tone as a putative factor contributing to dysregulation of the pituitary-adrenal axis and of metabolic processes in this phenotype. In the current study the hypothalamic CRF system in Zucker lean (FA/?) and obese (fa/fa) phenotypes was functionally evaluated. Neither the stalk median eminence content of CRF or arginine vasopressin (AVP) nor hypothalamic levels of CRF or AVP mRNA differed in the lean and obese phenotypes. No phenotypic differences were observed in either basal or stimulated CRF release from hypothalamic tissue obtained from lean and obese rats. Furthermore, in intact rats the magnitude of pituitary-adrenal responses to various stressors was also similar between phenotypes. However, secretion of CRF and AVP into the hypophysial-portal circulation of obese rats was, respectively, 73% and 35% lower than that of the lean rats. Adrenalectomy was associated with a 3-fold elevation of hypophysial-portal CRF levels in obese rats compared to intact controls. Corticosterone infusion was more effective in suppressing portal CRF levels in adrenalectomized obese compared to adrenalectomized lean rats. Finally, neither CRF receptor number and affinity nor the magnitude of pituitary-adrenal responses to rat CRF challenge (1 micrograms, iv) differed between Zucker phenotypes. These observations lead us to infer that rats of the obese phenotype exhibit reduced hypothalamic CRF tone due to dysregulation of the HPA axis at a site proximal to the hypophysiotropic CRF system that mediates glucocorticoid feedback regulation. PMID- 1312432 TI - Ectopic corticotropin-releasing hormone produced by a transfected cell line chronically activates the pituitary-adrenal axis in transkaryotic rats. AB - Hypothalamic CRH is the primary positive regulatory factor of the pituitary adrenal axis. The purpose of our study was to analyze the chronic effects of CRH on the production and secretion of POMC peptides from both the anterior lobe (AL) and neurointermediate lobe (NIL) of the pituitary by mimicking the syndrome of ectopic CRH secretion from neuroendocrine tumors. We first generated stably transfected W2 medullary thyroid carcinoma cell lines with a rat CRH expression vector under the transcriptional control of a cytomegalovirus gene promoter. These cell lines constitutively expressed the foreign gene, accurately processed the encoded prepro-CRH, and secreted biologically active CRH with an estimated potency equivalent to that of synthetic CRH-(1-41)NH2. The cell line designated W2CRH-7 was implanted sc in the syngeneic rat strain WAG/Rij and produced tumors that abundantly secreted CRH into the peripheral circulation. Four weeks postimplantation, W2CRH-7, but not wild-type W2, cells caused significant increases in the AL content of beta-endorphin-like immunoreactivity comparable to that caused by adrenalectomy (ADX). Plasma ACTH and serum beta-endorphin-like immunoreactivity were increased to a greater extent by ADX than by W2CRH-7 cell implantation. The NIL of both male and female rats showed either no change or a tendency to decreased beta-endorphin concentrations with no change in the acetylation or carboxy-shortening profiles judged by cation exchange chromatography in response to the ectopic CRH treatment. Rats of both sexes maintained a profound activation of the pituitary adrenal axis up to 16 weeks postimplantation, with normalized adrenal gland weights 5 times that of controls. The chronic secretion of CRH by W2CRH-7 cells resulted in a complete cessation of body growth in all rats up to the maximum time tested of 16 weeks. The lack of growth was partly ameliorated by concomitant ADX, suggesting an important role for adrenal glucocorticoids in these effects. We conclude that 1) the transplantable W2CRH-7 cell line provides a highly effective and reproducible means of sustained CRH treatment that mimics the syndrome of ectopic CRH expression by neuroendocrine tumors; 2) AL corticotrophs respond to chronic CRH by a sustained production and secretion of POMC peptides, leading to a marked adrenal cortical hyperplasia, with no evidence of biologically significant desensitization; 3) chronic CRH tends to decrease the NIL content of beta endorphin,with remarkably little effect on posttranslational processing; and 4) the syndrome of chronic ectopic CRH in WAG/Rij rats includes a cessation of body growth at least partly due to products of the adrenal glands. PMID- 1312433 TI - Endogenous excitatory amino acids and glutamate receptor subtypes involved in the control of hypothalamic luteinizing hormone-releasing hormone secretion. AB - These studies were designed to evaluate the actions and relative potencies of different endogenous and excitatory amino acid (EAA) selective analogs on EAA induced neuropeptide secretion as well as to analyze the receptor subtypes involved. For this purpose, different glutamate agonists were tested for their ability to evoke release of the hypothalamic neuropeptide LHRH from arcuate nucleus-median eminence (AN-ME) fragments incubated in vitro. Different glutamate agonists, i.e. 3-amino-3-hydroxy-5-methyl-isoxazole-4-propionic (AMPA), kainic, quisqualic, homocysteic (HCA), quinolinic (QUIN), N-methyl-D-aspartic (NMDA), and pyroglutamic (PYR) acids, elicited LHRH release from AN-ME fragments in vitro. Further evaluation of the range of activity of several of these compounds, both in terms of the dose inducing a half-maximal response and the LHRH-releasing effect at that particular dose, indicated that AMPA greater than HCA greater than QUIN greater than PYR, suggesting that non-NMDA receptors are primarily involved in EAA-induced LHRH release at the level of the AN-ME. Evaluation of the receptor types involved using two specific antagonists for NMDA and non-NMDA receptors, D,L-2-amino-7-phosphoheptanoic acid and 6,7-cyanoquinoxaline-2,3-dione, respectively, showed that the effects of AMPA and HCA on LHRH release can be completely blocked by 6,7-cyanoquinoxaline-2,3-dione, whereas QUIN activity was blocked by D,L-2-amino-7-phosphoheptanoic acid. The effects of PYR on LHRH release were abolished by both receptor blockers. The metabotropic receptor agonist trans-1-amino-cyclopentyl-1,1,3-dicarboxylic acid was not active in eliciting LHRH secretion. The data indicate that endogenous substances active at EAA receptor sites, such as HCA, QUIN, and PYR, can significantly increase the secretion of the neuropeptide LHRH and, thus, may participate in the physiological regulation of the activity of this important neuroendocrine neuronal system. In addition, the results suggest that non-NMDA receptor sites may be preferentially activated at lower ligand concentrations, although NMDA receptors may also be involved in the response to certain endogenous agonists. PMID- 1312434 TI - Effects of parathyroid hormone-related peptide on adenosine 3',5'-monophosphate and ornithine decarboxylase in a human colonic cell line. AB - PTH-related peptide (PTHrP) is widely distributed in normal tissues, including the gut, and is considered a potential autocrine or paracrine regulator of cellular growth and differentiation. With this in mind, a human colonic cell line (LoVo) was used to study the effect of PTHrP on ornithine decarboxylase (ODC), because ODC is known to have profound effects on the growth and differentiation of many cell types via stimulation of synthesis of polyamines. cAMP also was measured, because this second messenger has been implicated in the regulation of ODC activity. Nearly confluent LoVo cells, grown in F-12 medium and 10% fetal bovine serum (FBS), were preincubated in 1% FBS for at least 5 h, and then PTHrP (1-34) was added, and the incubation was continued for up to 6 h. Cell extracts were analyzed for ODC activity by measuring 14CO2 liberated from 14C-labeled ornithine, for cAMP by RIA, and for ODC mRNA by Northern analysis. PTHrP produced dose-related increases in both cAMP (2- to 3-fold) and ODC (3- to 5-fold), with a maximal effect at 0.1-1 microM and an ED50 of 1-10 nM. Comparison of the cAMP and ODC responses to PTHrP showed a strong correlation (r = 0.96; P less than 0.001). The effects of 1 microM PTHrP-(1-34) to increase cAMP and ODC were completely inhibited by 10-20 microM of the specific antagonist [Asn10,Leu11]PTHrP-(7-34). PTHrP-(1-34) did not stimulate ODC activity when cells were incubated without FBS. The stimulation of ODC activity by PTHrP-(1-34) was maximal at 2 h, a time at which an increase in ODC mRNA also was evident. PTH-(1-34) and forskolin also stimulated ODC activity, but PTHrP-(67-86) amide was ineffective. The results indicate that the N-terminal portion of the PTHrP molecule can stimulate ODC activity in a human colon cell line and that the effect is probably mediated by cAMP. The results are consistent with the idea that PTHrP may influence cell growth and differentiation in the gut via an effect on polyamine biosynthesis. Since LoVo cells also express PTHrP mRNA, this gastrointestinal cell line may serve as a useful model for studying autocrine regulation of gut cell growth and differentiation by PTHrP. PMID- 1312435 TI - Time course of the in vivo effects of thyroid hormone on cardiac gene expression. AB - The rate of response to thyroid hormone on cardiac growth, heart rate, and the relative changes in messenger RNA (mRNA) coding for alpha- and beta-myosin heavy chain (MHC), slow sarcoplasmic reticulum calcium-adenosine triphosphatase, and thyroid hormone receptors in ventricular tissue of hypothyroid rats was investigated. Hypothyroid rats had significantly smaller hearts, with slower heart rates and expressed no alpha-MHC mRNA as analyzed by an S1 nuclease protection assay when compared to euthyroid animals that expressed 79% alpha-MHC. Twelve hours after treating hypothyroid rats with 20 micrograms of L-T4, detectable levels of alpha-MHC mRNA were present and the shift to alpha-MHC mRNA was complete by 72 h of treatment. Northern blot analysis showed that hypothyroidism resulted in a 60% decrease in the level of sarcoplasmic reticulum calcium-adenosine triphosphatase mRNA which increased after 12 h of T4 administration and was 2.5-fold (P less than 0.05) greater than euthyroid levels after 72 h. In contrast, thyroid hormone receptor mRNA levels measured in poly(A)+ RNA were elevated in hypothyroid rats and decreased to euthyroid levels within 24 h after thyroid hormone treatment. These changes in cardiac gene expression occurred simultaneously with changes in both cardiac size and heart rate. The current studies characterize the coordinated changes and the time course for gene expression that occur in the hypothyroid heart after acute T4 administration. PMID- 1312436 TI - Expression of testicular 3 beta-hydroxysteroid dehydrogenase/delta 5----4 isomerase: regulation by luteinizing hormone and forskolin in Leydig cells of adult rats. AB - LH is required to maintain the activity of 3 beta-hydroxysteriod dehydrogenase/delta 5----4-isomerase (3 beta HSD) in testicular Leydig cells. The objective of the present study was to determine whether LH and effectors such as forskolin, which act via the intracellular cAMP signal transduction pathway, can regulate the expression of 3 beta HSD in rat Leydig cells in vitro. Primary cultures of Leydig cells were prepared from testes of adult rats and treated with oLH, forskolin, (Bu)2cAMP, or cholera toxin. The effects of treatment on 3 beta HSD activity were measured using [3 alpha-3H]dehydroepiandrosterone as substrate. Immunoreactive 3 beta HSD was quantified by denaturing sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting with a polyclonal antiserum against 3 beta HSD. The synthesis of 3 beta HSD was quantified after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitated cellular lysates of Leydig cells radiolabeled with L-[35S]methionine. The levels of 3 beta HSD mRNA were quantified by Northern analysis and hybridization with a cDNA encoding testicular 3 beta HSD (rat type I). A cell-free protein-synthesizing system was used to test the ability of 3 beta HSD mRNA to be translated into immunoreactive 3 beta HSD. 3 beta HSD activity increased 3.5- and 5.0-fold in Leydig cell cultures treated with forskolin (1 microM) and (Bu)2cAMP (1 mM), respectively, compared with control cultures. Maximal activity was attained after 48-72 h and maintained through 120 h of treatment. The increase in 3 beta HSD activity could be accounted for quantitatively by increases in the steady state levels and the rates of synthesis of 3 beta HSD. The cellular levels of immunoreactive 3 beta HSD increased 4.0- and 7.6-fold in Leydig cells treated with forskolin and (Bu)2cAMP, respectively. Moreover, both of these effectors increased by 6- to 8-fold the levels of newly synthesized 3 beta HSD after 24-72 h of treatment. Ovine LH, forskolin, cholera toxin, and (Bu)2cAMP increased the cellular levels of 3 beta HSD mRNA in a dose-dependent manner. The magnitude of the increases ranged from 2- to 42-fold, compared with that in control cultures, after 12 h of treatment. Maximal responses were effected by 1 ng/ml ovine LH, 1 microM forskolin, 1 ng/ml cholera toxin, and 1 mM (Bu)2cAMP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1312437 TI - Endothelin-1 suppression of rat adipocyte precursor cell differentiation in serum free culture. AB - The effect of endothelin-1 (ET-1) on differentiation of rat adipocyte precursor cells in serum-free culture and of the adipogenic fibroblast cell line TA1 was studied. ET-1 inhibited differentiation of rat adipocyte precursor cells into adipocytes in a dose-dependent fashion, while the peptide exerted no effect on TA1 cells. Rat adipose precursor cells possessed a single class of high affinity ET-1 receptor with a Kd of 0.71 nM and a binding capacity of 47,000 sites/cell. Affinity cross-linking of [125I]ET-1 showed two bands with molecular masses of 86 and 50 kilodaltons in rat adipose precursor cells and a single broad band with a molecular mass of 55-60 kilodaltons in TA1 cells. Pertussis toxin and the protein kinase-C inhibitors, H-7 and staurosporine, all of which enhanced adipocyte differentiation of rat adipose precursor cells, partially reversed ET-1 inhibition. These results showed the divergent effect of ET-1 on adipocyte conversion and indicated the possible involvement of a pertussis toxin-sensitive pathway and protein kinase-C at least in part in the inhibitory action of ET-1 on adipocyte differentiation. PMID- 1312438 TI - Cardiovascular responsiveness to parathyroid hormone (PTH) and PTH-related protein in genetic hypertension. AB - Hypertension is often accompanied by abnormalities of calcium homeostasis, including hyperparathyroidism with reduced target organ responses to PTH in kidney and bone. Due to this association between PTH and hypertension and since PTH and the paracrine factor PTH-related protein (PTHrp) have both been shown to exert marked changes in cardiovascular activity, these actions of PTH and PTHrp were examined in spontaneously hypertensive rats (SHR) and in control normotensive Wistar-Kyoto rats (WKY). Fourteen-week-old SHR [systolic blood pressure (SBP), 201 +/- 4.4 mm Hg] and WKY (SBP, 141 +/- 2.5 mm Hg) were studied. Renal cortical membranes were prepared and assayed for radioligand binding with [125I]PTH-(1-34) and [125I]PTHrp-(1-34). There was no apparent alteration in the affinity of the binding sites to either peptide in the SHR, but specific binding in SHR renal tissue was only 60% of that observed in WKY tissue for both peptides. Serum immunoreactive PTH levels were 4-fold higher in SHR than WKY, while serum total calcium and 1,25-dihydroxyvitamin D3 levels were not different. The iv administration of both PTH and PTHrp produced dose-dependent reductions in SBP and increases in heart rate in conscious unrestrained SHR and WKY. Both peptides caused greater absolute reductions in blood pressure in SHR than in WKY. However, when the hypotensive response was normalized for the higher baseline pressure in the SHR, the blood pressure reductions caused by PTH and PTHrp were not different in SHR and WKY. Conversely, the chronotropic responses to PTH and PTHrp were lower in SHR compared to WKY. These findings indicate that the SHR exhibits elevated PTH levels, with a reduced number of renal PTH/PTHrp receptors and a depressed chronotropic response to either PTH or PTHrp. In contrast, the hypotensive response to PTH or PTHrp was not altered, indicating possible tissue specific receptor subclasses or tissue-specific regulation of PTH and PTHrp receptors. PMID- 1312439 TI - Differential effects of platelet-derived growth factor isoforms on plasminogen activator activity in fetal rat osteoblasts due to isoform-specific receptor functions. AB - We examined receptor binding and metabolic effects of the platelet-derived growth factor (PDGF) isoforms AA, AB, and BB in cultures of osteoblastic cells from fetal rat calvaria. Saturation binding experiments demonstrated the presence of 6,000 binding sites for PDGF-AA, 42,000 for PDGF-AB, and 60,000 for PDGF-BB. Binding competition experiments were compatible with the recently postulated model of three PDGF receptor subtypes with differential affinity for the PDGF isoforms. The effects of the PDGF isoforms on DNA synthesis, collagen synthesis, and alkaline phosphatase activity in osteoblasts strictly correlated with the number of available binding sites. Accordingly, PDGF-BB was the most potent isoform, PDGF-AB was slightly less potent, and PDGF-AA was the least potent. In contrast, we found that PDGF-BB was less potent than PDGF-AB in increasing plasminogen activator activity in the osteoblast-conditioned medium. Our data strongly suggest that the PDGF receptor subtypes in fetal rat osteoblasts not only selectively bind one or more PDGF isoforms, but are also capable of responding differently to these isoforms. PMID- 1312440 TI - Bradykinin stimulates aldosterone release from cultured bovine adrenocortical cells through bradykinin B2 receptors. AB - The adrenal cortex contains a kallikrein-like enzyme that may lead to bradykinin (BK) formation. This study was designed to determine whether BK acts on adrenocortical cells to stimulate steroid secretion. BK, Lys-BK, a specific BK 2 (B2) receptor agonist, and desArg9-BK, a specific BK 1 (B1) receptor agonist, all stimulated aldosterone secretion from cultured bovine adrenal zona glomerulosa cells. BK and Lys-BK were equipotent (EC50 = 2 x 10(-9) M), whereas desArg9-BK was 1000-fold less potent. The maximal effects of BK and BK analogs were comparable to the maximal effects of adrenocorticotropin or angiotensin II. A B2, but not a B1, receptor antagonist inhibited BK-stimulated aldosterone release. Verapamil and N,N-diethylamino-octyl-3,4,5-trimethoxybenzoate, which reduce intracellular calcium concentrations, reduced BK-stimulated aldosterone secretion. Although BK stimulated both prostacyclin and aldosterone production, indomethacin abolished prostacyclin production without affecting aldosterone secretion. In cultured adrenal fasciculata cells, high concentrations of BK stimulated cortisol release, but B1 or B2 receptor agonists were not effective. BK-stimulated cortisol secretion was reduced by N,N-diethylamino-octyl-3,4,5 trimethoxybenzoate but not by indomethacin. In summary, BK stimulates aldosterone release from cultured adrenal glomerulosa cells via high affinity B2 receptors. The effect is calcium-dependent and independent of prostaglandins. BK also increases cortisol release; however, this stimulation requires high concentrations of BK and may be mediated by an unknown receptor or by a receptor independent mechanism. PMID- 1312441 TI - Beta-adrenergic and peptide N-terminal histidine and C-terminal isoleucine stimulation of N-acetyl-transferase activity and melatonin production in the cultured rat pineal gland. AB - The purpose of this investigation was to compare the effect of peptide N-terminal histidine and C-terminal isoleucine (PHI) with that of the beta-adrenergic agonist isoproterenol (ISO) on N-acetyltransferase (NAT) activity and melatonin production in the cultured rat pineal gland. Pineal glands were removed and placed in organ culture containing PHI, ISO, or PHI plus ISO at different dosages, and subsequent changes in NAT activity and melatonin levels were measured. PHI stimulated these parameters in both a time- and dose-dependent manner. Combined treatment with PHI (10(-6) M) and high doses of ISO (either 10( 7) or 10(-8) M) did not potentiate the effect of the peptide in terms of either NAT activity or melatonin levels in the pineal gland. However, at a lower concentration, ISO (10(-9) M) had additive effects to those of PHI in both cultured pineals and medium. The results suggest that PHI modulates melatonin synthesis in the rat pineal gland. Furthermore, stimulation of the pineal with both PHI and ISO demonstrates an additive effect rather than a synergistic action of these compounds. It is presumed that ISO and PHI stimulate pineal melatonin production via separate receptors, but they probably use the same intracellular second messenger, cAMP, to do so. This is the first study showing an effect of the peptide PHI on pineal melatonin production in any vertebrate. PMID- 1312442 TI - Activin-A stimulates the synthesis of gonadotropin-releasing hormone receptors. AB - The number of GnRH receptors on gonadotropes is regulated by GnRH as well as by heterologous modulators. We have used the density shift technique to measure the synthetic rate of GnRH receptors in pituitary cell cultures and found it to be stimulated by GnRH, an action that is antagonized by inhibin. In the present study, we evaluated the effects of activin-A on the GnRH receptor synthesis rate as well as effects of activin on stimulation of GnRH receptor synthesis by the homologous hormone. Recombinant human activin-A (50 ng/ml) was incubated with pituitary cell cultures from female weanling rats and the incorporation of densely labeled amino acids into receptors for GnRH was measured. The rate of GnRH receptor synthesis of cells treated with activin (50 ng/ml) together with either GnRH (0.1 ng/ml) or inhibin (12 ng/ml) was also quantified. Activin significantly stimulated the synthetic rate of GnRH receptors similarly to that observed after GnRH treatment (time for synthesis of half the population of GnRH receptors was 12.6 +/- 1.1, 16.1 +/- 1.3 vs. 28.3 +/- 1.2 h for GnRH, activin, and control, respectively), although the time course for stimulation by GnRH and activin appeared to differ. Inclusion of activin in cultures did not affect homologous stimulation of GnRH receptor synthesis. The stimulatory effects of activin were unaffected by combined treatment with inhibin (t1/2 of synthesis 17.2 +/- 2.0 h). Together, these data indicate that activin stimulates GnRH receptor synthesis in cell culture through a distinct mechanism from GnRH. Additionally, inhibin did not antagonize the stimulatory effects of activin on synthesis of GnRH receptors. This is, to our knowledge, the first demonstration of an action of activin-A on GnRH receptor synthesis. PMID- 1312443 TI - Lymphocyte-derived adrenocorticotropin is insufficient to stimulate adrenal steroidogenesis in hypophysectomized rats. AB - Cells of the immune system can produce and respond to peptide hormones associated with the endocrine system. However, the physiological significance of these endocrine-immune interactions is not known. It has been postulated that cells of the immune system, when stimulated with viruses that induce interferon-alpha, produce sufficient levels of ACTH to stimulate adrenal steroidogenesis and, thus, function as an auxiliary source of ACTH that may have a role in the response to stress. However, we have confirmed that levels of ACTH-related peptides produced by immunocompetent cells are far lower than those produced by the pituitary, raising questions about the ability of lymphocyte-derived ACTH to stimulate adrenal function. Furthermore, we have rigorously examined this issue using intact and hypophysectomized rats treated with Newcastle disease virus. Although high levels of interferon-alpha were produced by both intact and hypophysectomized rats, and the plasma corticosterone concentration increased dramatically in intact animals, corticosterone remained undetectable in hypophysectomized rats. The lack of a corticosterone response in these animals was not due to adrenal insensitivity to ACTH, as shown by a normal rise in corticosterone following Cosyntropin injection 8 h after hypophysectomy. The findings demonstrate that levels of ACTH produced by nonpituitary sources in response to viral infection are not sufficient to stimulate adrenal steroidogenesis. PMID- 1312445 TI - Regulation of the adrenal renin angiotensin system in cultured bovine zona glomerulosa cells: effect of catecholamines. AB - The renin-angiotensin system consists of two main enzymes, renin and angiotensin converting enzyme, which lead to the formation of angiotensin-II. Angiotensin-II is a potent vasoconstrictor and stimulates the production of aldosterone. In this study we examined the effect of ACTH, potassium, (Bu)2cAMP (dbcAMP), and catecholamines on the adrenal renin-angiotensin system. To study the production of renin and aldosterone in vitro, we developed a monolayer culture of bovine zona glomerulosa cells in serum-free medium. Collagenase-dispersed zona glomerulosa cells were incubated in Pasadena Foundation for Medical Research-4 medium containing 10% fetal calf serum for 72 h, and the medium was replaced with serum-free medium for the next 24 h of the experimental period. The cells during this 24 h were exposed to various doses of ACTH, potassium, dbcAMP, and sympathomimetic agents. ACTH and dbcAMP stimulated aldosterone secretion, and this secretion was associated with an increase in renin activity in cells and medium. Aldosterone was also stimulated by high doses of potassium, and potassium had a stimulatory effect on the secretion of renin in medium. Catecholamines had a weak stimulating effect on aldosterone secretion and were potent stimulators of adrenal renin activity in cells and medium. Dopamine had no significant effect on basal aldosterone secretion or renin activity in cells and medium. In conclusion, these data indicate that adrenal renin is synthesized in bovine zona glomerulosa cells in vitro, and that ACTH and dbcAMP stimulate adrenal renin and aldosterone production. Furthermore, adrenal renin, like renal renin, may be under the control of the sympathetic nervous system. PMID- 1312444 TI - Solubilization of high affinity peptide-YY receptors from porcine brain. AB - We have previously characterized peptide-YY (PYY) receptors in porcine hippocampal membranes. We demonstrate here that brain PYY receptors can be extracted in the active state using digitonin. Among several detergents tested for their suitability to extract active PYY receptors, digitonin gave the most favorable results, as judged by specific binding of [125I]PYY to the solubilized receptors. The binding of [125I]PYY to digitonin extract was dependent on incubation time, temperature, and protein and magnesium ion concentrations and had a pH optimum of 6-7. Solubilized PYY receptors maintained the rank order of potencies for various related peptides and PYY fragments characteristic of the membrane PYY receptor: PYY greater than neuropeptide Y (NPY) much much greater than avian and porcine pancreatic polypeptide, and PYY greater than PYY-(22-36) much much greater than PYY-(1-22) and PYY-(22-28), respectively. Scatchard analyses of competitive binding data indicated the presence of two classes of binding sites in the digitonin extract; the high affinity component had affinities and binding capacities similar to those of the membrane PYY receptor. Solubilized PYY receptors also retained their sensitivity to guanine nucleotides. PYY was cross-linked to its receptors with disuccinimidyl suberate, solubilized with digitonin, and cross-linked to digitonin-solubilized receptors. The resulting complexes were analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. Using these procedures, we identified a PYY receptor species with a molecular size of 50,000, which was the same size as the labeled protein in native membrane homogenates. Solubilized NPY receptors were also the same size. The solubilized cross-linked PYY receptor was adsorbed by wheat germ agglutinin-agarose and Concanavalin-A, suggesting its glycoprotein nature. These data suggest that the specific binding properties of the PYY receptor are inherent in the solubilized glycoprotein molecules. The solubilization in digitonin of PYY receptors from membranes should allow a more complete molecular and functional characterization of PYY-mediated events and purification of the receptor. PMID- 1312446 TI - Differential regulation of the rat melatonin receptors: selective age-associated decline and lack of melatonin-induced changes. AB - To gain some understanding of the factors regulating high affinity melatonin (MT) receptors in the rat, we conducted a series of studies using quantitative autoradiography of [2-125I]iodo-MT binding in vitro with validated assay conditions. MT receptor status and the relative protein content of the autoradiographic sections were assessed in the anterior pituitary gland, the area postrema, the caudal (tail) artery (CA), the anterior cerebral artery (ACA), and the suprachiasmatic nuclei (SCN) of 9-, 96-, and 306-day-old Wistar rats. When age-associated changes in protein content were taken into account, MT receptor expression in the area postrema and the SCN remained relatively constant between 9-306 days of age. On the contrary, a dramatic loss of MT receptors was observed in the arteries of 306-day-old rats (98% and 89% loss compared to the 9-day-old rats in the ACA and CA, respectively). In the anterior pituitary gland, MT receptors were expressed only in the 9-day-old rats. The above changes reflected major changes in binding capacity and minor changes in binding affinity. Neither removal of endogenous circulating MT (acute light exposure for 24 h, pinealectomy, or superior cervical ganglionectomy) nor MT injections (1 mg/kg for 10 days 6 h after lights on) affected MT receptor status in the ACA, CA, area postrema, or SCN. Our data suggest that MT receptor expression is differentially regulated during development and that permanent alterations in MT levels do not affect rat MT receptor status. PMID- 1312447 TI - Inhibition of 25-hydroxyvitamin D3-24-hydroxylase by forskolin: evidence for a 3',5'-cyclic adenosine monophosphate-independent mechanism. AB - Forskolin has long been used to demonstrate the involvement of cAMP in the regulation of cellular function, by virtue of its ability to stimulate adenylate cyclase directly. Recently, however, forskolin has been shown to affect plasma membrane transporter and channel function in a manner unrelated to cAMP. The present study examines whether forskolin-mediated inhibition of a mitochondrial membrane-associated enzyme, 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), also occurs by a cAMP-independent mechanism. Both forskolin and PTH stimulated cAMP accumulation and inhibited 24-hydroxylase activity in a dose-dependent manner in fresh mouse renal tubules. However, the level of inhibition of 24 hydroxylase achieved with forskolin was consistently greater than that obtained with PTH, at comparable levels of cAMP. 1',9'-Dideoxyforskolin, a cyclase inactive analog of forskolin, also inhibited 24-hydroxylase activity, without stimulating cAMP production. Moreover, both forskolin and 1',9'-dideoxyforskolin directly inhibited 24-hydroxylase in isolated renal mitochondria. Kinetic analysis revealed a competitive mode of inhibition for both agents; however, 1',9'-dideoxyforskolin proved to be a more potent inhibitor of 24-hydroxylase than forskolin (inhibitory constant, 0.25 vs. 22 microM, respectively). Finally, both forskolin and 1',9'-dideoxyforskolin also inhibited inducible 24-hydroxylase in renal tubules prepared from 1,25-(OH)2D3-treated mice. However, inducible 24 hydroxylase activity was less susceptible to inhibition by the diterpenes than the basal enzyme activity. The present study provides evidence for cAMP independent inhibition of 24-hydroxylase by forskolin and represents the first demonstration of a cAMP-independent effect of forskolin on a protein that is not a plasma membrane-associated transporter or channel. Our data advocate caution in the interpretation of studies using forskolin to assess the role of cAMP in cellular processes. PMID- 1312448 TI - Melatonin signal transduction and mechanism of action in the central nervous system: using the rabbit cortex as a model. AB - The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particularly abundant is the parietal cortex. Consequently, we characterized the putative melatonin receptor in the parietal cortex by a series of in vitro ligand-receptor binding experiments and biochemical and electrophysiological studies. The in vitro saturation and competition experiments demonstrated that the binding in the crude cortical membrane preparations was of high affinity and specificity. Guanine nucleotides (GDP, GTP, and GTP gamma S) inhibited the specific 2-[125I]iodomelatonin binding in a dose-dependent manner. Coincubation with a nonhydrolyzable GTP analog provoked a shift in the binding affinity; the numerical values of the Kd increased from 20-30 to 200-600 pM. Melatonin, in nanomolar concentrations, was able to inhibit the forskolin stimulated accumulation of cAMP in parietal cortex explants, and preincubation with pertussis toxin counteracted this effect of melatonin. Apparently, the melatonin binding site in the rabbit parietal cortex is linked to its second messenger via a pertussis toxin-sensitive G-protein, probably of the inhibitory Gi class, similar to what has been described for different parts of the brain of other vertebrates. The experiments on the spontaneous firing activity of single neurons in the third to fourth layer of the parietal cortex in anesthetized animals showed that melatonin and its potent agonist 2-iodomelatonin exhibited gamma-aminobutyric acid (GABA)-like effects and were able alone, in nanomolar concentrations, to significantly slow the neuronal firing activity. Moreover, both melatonin and 2-iodomelatonin potentiated the effect of GABA on the neuronal activity, leading to powerful inhibition of the tested neurons. Undoubtedly, the binding site in the rabbit parietal cortex possesses all of the characteristics of a functional receptor. We suggest that melatonin is involved in the control of fundamental cortical functions and that it acts in concert with GABA, one of the two major inhibitory neurotransmitters in the central nervous system. PMID- 1312449 TI - Oxytocin at physiological concentrations evokes adrenocorticotropin (ACTH) release from corticotrophs by increasing intracellular free calcium mobilized mainly from intracellular stores. Oxytocin displays synergistic or additive effects on ACTH-releasing factor or arginine vasopressin-induced ACTH secretion, respectively. AB - The potency of oxytocin (OT) in evoking ACTH secretion by isolated, superfused rat adenohypophyseal corticotrophs and its enhancement by CRF and arginine vasopressin (AVP) were analyzed. Each secretagogue effectively released ACTH from adenohypophyseal cells when added separately in pulsatile fashion in physiological concentrations based on hypophyseal portal blood (OT, 10 nM; AVP, 0.5 nM; CRF, 0.1 nM). OT released ACTH at concentrations as low as 1 nM. Moreover, a dose-response relationship up to 10 microM was revealed. Combinations of a constant amount of CRF (0.1 nM) with increasing concentrations of OT exerted a synergistic effect on ACTH release. In contrast, OT given in various concentrations in combination with AVP (0.5 nM) produced an additive effect on ACTH release. To study the mechanism of action of OT on ACTH secretion, cytosolic free calcium levels in single pituitary cells exposed to OT or AVP were measured using the calcium-sensitive fluorescent indicator Fura-2. Corticotrophs among mixed adenohypophyseal cell types in the primary cultures were identified by immunocytochemistry. More than 500 cells were individually stimulated with OT or AVP. Basal cytosolic free calcium levels ranged between 80-130 nM free calcium. The addition of 100 nM OT or 1 microM AVP increased the cytosolic free calcium concentration within 3 sec to values ranging from 500-800 nM. An increase in intracellular calcium ranging from 200-500 nM due to OT could still be observed after extracellular calcium depletion. Taken together, our data demonstrate that physiological concentrations of OT stimulate ACTH secretion, independent of the other ACTH secretagogues, by mobilizing calcium mainly from intracellular stores. PMID- 1312450 TI - Inactivation of early glucocorticoid feedback by corticotropin-releasing factor in vitro. AB - We have investigated the interaction between hypothalamic ACTH secretagogues and adrenocortical glucocorticoids in rat anterior pituitary tissue using an in vitro perifusion system. Repeated 5 min pulses of 41-residue CRF (CRF-41) or arginine vasopressin (AVP) were applied at 1 h intervals for up to 7 h. Administration of 0.1 microM corticosterone 30 min before and during the 5 min 0.1 nM CRF-41 stimulus at 5 h resulted in a significant inhibition of CRF-41 stimulated ACTH release within 30 min. Inhibition of ACTH release also developed if no CRF-41 stimulus was applied in conjunction with steroid at 5 h. In contrast, if the exposure to corticosterone (0.1 microM, 35 min total duration) was started simultaneously with the application of CRF-41 at 5 h, no inhibition of ACTH release ensued. Similarly, no inhibition of CRF-41-stimulated ACTH release was observed when corticosterone was started simultaneously with a 5 min pulse of cyclic 8-(4-Chlorophenylthio) AMP (8-CPT-cAMP), a cell membrane permeant analog of cAMP. In contrast to CRF-41 and 8-CPT-cAMP, AVP failed to modify glucocorticoid-induced inhibition of AVP- or CRF-41-stimulated ACTH release. Moreover, CRF-41 did not prevent the glucocorticoid-induced inhibition of AVP stimulated ACTH release. In summary: 1) CRF-41 inactivates early glucocorticoid inhibition of CRF-41-stimulated ACTH secretion, and this is mimicked by a cell membrane permeant analog of cAMP; 2) AVP does not inactivate glucocorticoid induced inhibition of stimulated ACTH release; 3) the data point to an acute interaction between the cAMP/protein kinase A and glucocorticoid-responsive intracellular pathways. Such differential modulation of feedback inhibition by CRFs may be of functional importance in vivo. PMID- 1312451 TI - Rat Leydig cells bind platelet-derived growth factor through specific receptors and produce platelet-derived growth factor-like molecules. AB - The platelet-derived growth factor (PDGF) is a major mitogen for cells of mesenchymal origin. Because Leydig cells arise from mesenchymal precursors, we tested the hypothesis that these cells might be a target for PDGF. We also investigated a possible production of a PDGF-like substance by Leydig cells in culture and the distribution of PDGF-like material in the rat testis using immunohistochemistry. PDGF was found to bind specifically to high affinity receptors on the surface of purified adult rat Leydig cells. Conditioned medium from cultured Leydig cells competed with 125I-labeled PDGF for binding to the Leydig cells. The secretion of PDGF receptor-competing activity was stimulated in a dose-dependent manner by the trophic hormone hCG. Immunohistochemical studies revealed specific staining for PDGF in the Leydig cells of adult rat testis. Taken together these observations suggest that PDGF may play a role in the local control mechanisms of testicular function. PMID- 1312452 TI - Bidirectional regulation of the 1,25-dihydroxyvitamin D3 receptor by phorbol ester-activated protein kinase-C in osteoblast-like cells: interaction with adenosine 3',5'-monophosphate-induced up-regulation of the 1,25-dihydroxyvitamin D3 receptor. AB - In the present study the involvement of protein kinase-C (PKC) in the regulation of the vitamin D receptor (VDR) and interaction of PKC with cAMP-induced up regulation of VDR in osteoblast-like cells were examined. Activation of PKC by incubation for 4 h with the phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in a comparable dose-dependent decrease in 1,25-dihydroxyvitamin D3 binding in the osteoblast-like cell lines UMR 106 and ROS 17/2.8, with a maximum inhibition at 100 nM and an IC50 at 5 nM PMA. Time-course studies revealed that in both UMR 106 and ROS 17/2.8 cells, 24-h incubation with PMA caused an increase in 1,25-dihydroxyvitamin D3 binding. This can be related to down-regulation of PKC. Scatchard analysis demonstrated that activation of PKC resulted not in a change in receptor affinity, but, rather, in an increase in VDR number. This is supported by Northern blot analysis, which shows at 2 h a decrease and at 24 h an increase in VDR mRNA. At 4 h, when activation of the cAMP pathway results in an increase in VDR, activation of PKC results in a decrease in VDR. Coincubation for 4 h with PMA caused a decrease in PTH- and forskolin-induced up-regulation of VDR. This inhibition is not due to a reduction in cAMP production, as PTH stimulated cAMP production was potentiated by PMA. The effect of activation of PKC on VDR is not a general effect, as PMA does not affect basal ornithine decarboxylase activity and potentiates PTH-induced ornithine decarboxylase activity. The present study demonstrates that PKC is involved in the regulation of VDR in UMR 106 and ROS 17/2.8 and that PKC interacts with cAMP in the regulation of VDR. The current data point to a negative controlling role for PKC in the regulation of VDR. Moreover, two different cAMP-regulated actions in UMR 106 cells (VDR up-regulation and ornithine decarboxylase activity) are differently modulated by PKC. Although the precise mechanism by which PKC represses and stimulates gene expression is not yet clear, this study demonstrates the important regulatory role for PKC in two osteoblast-like sarcoma cell lines. PMID- 1312453 TI - Effect of chronic active immunization anti-corticotropin-releasing factor on the pituitary-adrenal function in the sheep. AB - ACTH and cortisol diurnal variations and responses to two types of stress (insulin-induced hypoglycemia and isolation-restraint stress) or to an acute injection of lysine-vasopressin were studied in intact and anti-corticotropin releasing factor (CRF) actively immunized rams. Immunization was obtained by the injection of synthetic ovine CRF coupled to BSA with carbodiimide. All animals developed antibodies anti-CRF and displayed an alteration of their general condition and a body weight reduction. The mean basal ACTH and cortisol secretion as well as the number and mean amplitude of diurnal pulses of these hormones was significantly reduced in the group of anti-CRF immunized rams. However, the reduction in all three parameters was much more pronounced for cortisol than for ACTH. No ACTH and cortisol response to insulin-induced hypoglycemia and isolation restraint stress was observed. The stimulating action of lysine-vasopressin on ACTH release was significantly reduced as compared to controls. These results indicate that CRF is a major physiological component of the ovine hypothalamo hypophysial-adrenal axis and participates in the events that regulate ACTH and cortisol diurnal variations and response to stress. PMID- 1312454 TI - Basic fibroblast growth factor: an autocrine mitogen of rat thyroid follicular cells? AB - Basic fibroblast growth factor (FGF) is a mitogen for the rat thyroid cell line FRTL-5. A possible autocrine role for this growth factor has been investigated in rat thyroid follicular cells both in vitro and in vivo. We report here the synthesis and localisation of basic FGF and one of its high affinity receptors (flg) in FRTL-5 cells, shown by Northern hybridization analysis, Western blotting, and immunohistochemistry. Two major species of basic FGF mRNA of approximately 2.2 and 7.0 kilobases and one major species of flg mRNA of approximately 4.2 kilobases were identified in FRTL-5 cells. The basic FGF immunoreactivity observed histologically was attributed to a heparin-binding protein of approximately 20 kilodaltons mol wt. The physiological relevance of basic FGF to the thyroid is underlined by the demonstration of significant stores of immunoreactive protein, predominantly in the basement membrane of thyroid follicular cells, in paraffin sections of the normal rat thyroid, although basic FGF mRNA was not detected by in situ or Northern hybridization analysis. The mitogenic response of FRTL-5 cells to human recombinant basic FGF has been further characterized, and the factor shown to stimulate with an ED50 of 4 ng/ml. The mitogenic effects of exogenously supplied and endogenously produced basic FGF were shown to be potentiated by heparin. Examination of the mitogenic activity of both exogenous and endogenous basic FGF and its immunoneutralization in vitro suggests that locally produced basic FGF may be an important autocrine regulator of thyroid follicular cell growth. PMID- 1312455 TI - Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and EGF and PDGF beta-receptors in human endometrial tissue: localization and in vitro action. AB - Human endometrial tissue and primary stromal cell culture contain immunoreactive epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-AB as well as EGF and PDGF-beta receptors. The immunostaining for EGF, EGF receptor, and PDGF beta-receptor were associated with endometrial luminal and glandular epithelial and stromal cells, whereas only the stromal cells contain immunoreactive PDGF-AB. The immunostaining intensity of EGF, EGF receptor, and PDGF-AB was similar in both phases of the menstrual cycle, whereas, PDGF-beta receptor immunostaining was highest in proliferative phase and considerably reduced, particularly in luminal and glandular epithelial cells in the secretory phase. In addition primary stromal cell cultures express EGF, PDGF-AB, and contain EGF and PDGF-beta receptors, and very low levels of PDGF-alpha receptor. 3H-Thymidine incorporation indicate that after 48 h of incubation in serum-free medium approximately 75-80% of stromal cells are quiescent. Incubation of quiescent stromal cells with 10% fetal bovine serum stimulate 3H-thymidine incorporation in a time-dependent manner reaching maximal after 30-48 h, with a doubling time of 38.2 h. EGF (1.5-15 ng/ml) stimulates 3H-thymidine incorporation by quiescent stromal cells (P less than 0.001). This effect was significantly reduced at concentrations above 15 ng/ml (P less than 0.005). PDGF-AB (3-10 ng/ml) and PDGF-BB (0.5-10 ng/ml) also stimulate 3H-thymidine incorporation in quiescent stromal cells compared to controls (P less than 0.005). The action of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) was time dependent, reaching maximal after 36 and 48 h of incubation (P less than 0.002). Addition of PDGF-AB (10 ng/ml) to EGF (15 ng/ml) significantly enhanced the action of EGF or PDGF-AB used individually (P less than 0.001). 17 beta-estradiol or progesterone at 1 microM did not stimulate 3H-thymidine incorporation, although they were stimulatory in combination (P less than 0.001), they did not alter the action of EGF or PDGF when added in combination. These observations provide further evidence that human endometrial tissue contains specific immunoreactive EGF receptors. It also demonstrates the presence of immunoreactive EGF, PDGF-AB, and PDGF-beta receptors in endometrial tissue as well as stromal cells in primary culture. Both EGF and PDGF are mitogenic for endometrial stromal cells, suggesting an autocrine/paracrine role in modulation of endometrial cell growth and differentiation. PMID- 1312456 TI - Heterogeneous intracellular free calcium responses to parathyroid hormone correlate with morphology and receptor distribution in osteogenic sarcoma cells. AB - The osteogenic sarcoma cell line UMR 106-01 exhibits heterogeneous morphology and hormone response in subconfluent monolayer cultures. In these studies we have explored the correlation between morphological profiles and patterns of cytosolic calcium [Ca2+]i response to PTH and other agonists in single UMR 106-01 cells loaded with the Ca(2+)-sensitive fluorescent indicator, fura-2. Realtime recording of [Ca2+]i revealed that PTH (10(-7) M) produced a transient [Ca2+]i rise in 19% of the cells studied. [Ca2+]i transients were also induced by prostaglandins E2 and F2 alpha, and fetal bovine serum, but with different response frequencies (20%, 12%, and 58%, respectively). Spatial resolution of changes in [Ca2+]i by video image analysis revealed that the response to PTH was more frequent in large polygonal cells with long cytoplasmic processes and less common in smaller cells growing in clusters, whereas there was no clear subtype specificity for the effects of epidermal growth factor and fetal bovine serum on [Ca2+]i. Autoradiographic analysis of cell monolayers demonstrated a higher density of PTH-binding sites on cells with cytoplasmic extensions, whereas epidermal growth factor-binding sites were largely on colony-forming cells. Thus, the [Ca2+]i response to hormonal stimulation is heterogeneous within UMR 106-01 cell populations and within single cells, and it correlates with receptor density. This suggests that osteoblastic cells respond to PTH by activation of changes in [Ca2+]i only at certain specific steps during osteoblast development or stages of the cell cycle. PMID- 1312457 TI - Norepinephrine stimulates immunoreactive (ir) atrial natriuretic peptide (ANP) secretion and pro-ANP mRNA expression from rat hypothalamic neurons in culture: effects of alpha 2-adrenoceptors. AB - Although ANP or its smaller congeners are produced and secreted from rat hypothalami, the role or roles of neurotransmitter(s) in regulating their release and production from the neurons remains unclear. We report here that norepinephrine or epinephrine (NE/EPI) facilitates irANP secretion and pro-ANP mRNA expression in long term cultures of rat hypothalamic neurons through their effects on alpha 2-adrenoceptors. Hypothalami of 3 day-old Sprague-Dawley rats were removed and digested with collagenase. The dispersed cells were plated on poly-D-lysine coated culture dishes (10(6) cells/well) in Hepes buffered Dulbecco's Modified Eagle Medium supplemented with 8% fetal calf serum. Six days after plating, media were replenished with serum free media and the cultures incubated for 4 more days with vehicle or various doses of NE, EPI, alpha- or beta-adrenoceptor agonists in the presence of absence of antagonists. Culture media were then extracted with C18 Sep-pak and the levels of irANP determined by a well characterised RIA for ANP. NE or EPI treatment significantly increased irANP secretion from the cultures in a dose related manner with ED50 and Emax of approximately 0.2 microM and 1 microM respectively. The stimulation effect of NE was blocked by yohimbine (alpha 2-antagonist), but not prazosin (alpha 1 antagonist) or propranolol (beta-antagonist). Clonidine (alpha 2-agonist), but not phenylephrine (alpha 1-agonist) or isoprenaline (beta-agonist) mimicked the effects of NE or EPI. At the concentration of 0.1 microM, clonidine increased irANP release approximately 3 fold above that of control values (34.7 +/- 3.3; mean +/- SE, n = 4). These changes were accompanied by corresponding increments in the abundance of pro-ANP mRNA in the cultures as examined by a colorimetric Northern blot analysis. Our results indicate that NE or EPI, acting through its alpha 2-adrenoceptors, may modulate the function of ANP neurons in rat hypothalami by regulating the secretion and production of the neuropeptide at the genomic level. PMID- 1312458 TI - Excitatory amino acids modulate phosphoinositide signal transduction in human epileptic neocortex. AB - Stimulation of phosphoinositide (PI) hydrolysis by norepinephrine (NE), carbachol (Carb), and excitatory amino acids (EAAs) was measured in slices prepared from neocortex excised during epilepsy surgery. NE and Carb markedly enhanced PI turnover (EC50: NE, 12 microM; Carb, 661 microM) as reflected by [3H]inositol monophosphate (IP1) accumulation in tissue slices prelabeled with [3H]myoinositol. These effects were dose-dependent, saturable, and five to six times higher than basal IP1 accumulation. A weaker stimulation (twofold) was observed with quisqualate (QUIS; EC50, 1.1 microM) and glutamate (GLU; EC50, greater than 1 mM), while minimal or no stimulation was seen with kainate (KA) and N-methyl-D-aspartate (NMDA). Agonist-stimulated PI turnover was significantly reduced in samples from actively spiking epileptic neocortex versus nonspiking areas as defined by electrocorticography (NE, -23%, p less than 0.05; Carb, -44%, p less than 0.01). Preincubation of slices with various EEAs inhibited Carb induced IP1 formation. The maximal extent of inhibition (1 mM) was both amino acid-dependent (IC50: NMDA, 5 microM; KA, 3.3 microM; QUIS, 47 microM; GLU, greater than 1 mM). These data suggest that epileptic activity modulates PI metabolism and alters receptor-effector coupling. As important mediators of epileptogenesis, EAAs may interfere++ with the efficiency of this second messenger system. PMID- 1312459 TI - Magnetic resonance imaging in infantile spasms: effects of hormonal therapy. AB - Magnetic resonance imaging (MRI) was performed on five patients with infantile spasms who were treated with relatively low doses of adrenocorticotrophic hormone (ACTH) to study the extent of brain shrinkage induced by ACTH therapy. MRI prior to ACTH therapy revealed periventricular hyperintensity (PVH) areas and poor myelination in four patients. In one case, MRI performed 2 days after initiation of ACTH therapy also showed PVH and poor myelination. Brain shrinkage was observed 2 weeks after initiation of ACTH therapy. The most impressive follow-up finding upon MRI was the decrease in PVH found in four patients. The differentiation between myelinated white matter and surrounding cortex became poorer in three cases. Cortical atrophy progressed in all patients but ventricular dilation progressed in only one patient. At the end of ACTH therapy, ventricular dilation progressed in all cases. These findings suggest that loss of water not only from periventricular white matter but also from cortex is the main etiological factor of brain shrinkage induced by ACTH. PMID- 1312460 TI - Evolution of the nuclear receptor gene superfamily. AB - Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplication from a common ancestor or if their different domains came from different independent sources. To test these possibilities we have constructed and compared the phylogenetic trees derived from two different domains of 30 nuclear receptor genes. The tree built from the DNA binding C domain clearly shows a common progeny of all nuclear receptors, which can be grouped into three subfamilies: (i) thyroid hormone and retinoic acid receptors, (ii) orphan receptors and (iii) steroid hormone receptors. The tree constructed from the central part of the E domain which is implicated in transcriptional regulation and dimerization shows the same distribution in three subfamilies but two groups of receptors are in a different position from that in the C domain tree: (i) the Drosophila knirps family genes have acquired very different E domains during evolution, and (ii) the vitamin D and ecdysone receptors, as well as the FTZ-F1 and the NGF1B genes, seem to have DNA binding and hormone binding domains belonging to different classes. These data suggest a complex evolutionary history for nuclear receptor genes in which gene duplication events and swapping between domains of different origins took place. PMID- 1312461 TI - Demonstration of retrotransposition of the Tf1 element in fission yeast. AB - Tf1, a retrotransposon from fission yeast, has LTRs and coding sequences resembling the protease, reverse transcriptase and integrase domains of retroviral pol genes. A unique aspect of Tf1 is that it contains a single open reading frame whereas other retroviruses and retrotransposons usually possess two or more open reading frames. To determine whether Tf1 can transpose, we overproduced Tf1 transcripts encoded by a plasmid copy of the element marked with a neo gene. Approximately 0.1-4.0% of the cell population acquired chromosomally inherited resistance to G418. DNA blot analysis demonstrated that such strains had acquired both Tf1 and neo specific sequences within a restriction fragment of the same size; the size of this restriction fragment varied between different isolates. Structural analysis of the cloned DNA flanking the Tf1-neo element of two transposition candidates with the same regions in the parent strain showed that the ability to grow on G418 was due to transposition of Tf1-neo and not other types of recombination events. PMID- 1312462 TI - Symmetry, flexibility and permeability in the structure of yeast retrotransposon virus-like particles. AB - The virus-like particles (VLPs) of the yeast retrotransposon Ty are genetically, structurally and functionally analogous to retroviral nucleocapsids or cores. Like retroviral cores Ty-VLPs package and possibly promote the enzyme activities for reverse transcription and integration, as well as encapsulating the RNA that is the intermediate in retrotransposition. Here we show that Ty-VLPs assemble into symmetrical structures across a broad distribution of particle sizes. This spread of sizes violates the principle of quasi-equivalent packing. In addition, RNase accessibility experiments suggest that these particles form an open structure that does not protect the encapsulated RNA. These features distinguish Ty-VLPs from typical spherical viral capsids in both structure and function. PMID- 1312463 TI - A nuclear matrix attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain. AB - The extrachromosomal Epstein-Barr virus (EBV) plasmid in the Burkitt lymphoma cell line, Raji, is stably associated with the nuclear matrix. This association is effected by a nuclear matrix attachment region (MAR) located in the BamHI C fragment of the viral genome; no other region of EBV DNA was found to be attached to the nuclear matrix with high affinity. The MAR was mapped to 5.2 kbp of DNA, greater than 80% of which is found on the nuclear matrix in unsynchronized cells expressing only viral latent cycle products. Thus the majority of viral plasmids in Raji cells use the same MAR. The MAR of EBV DNA contains the origin of latent viral DNA replication (oriP), the genes for the small viral RNAs (EBERs) and a 500 bp region immediately upstream of the EBER-1 gene. The clustering of the latent viral replication origin and the nearby enhancer and promoters for latent viral transcription on the nuclear matrix is likely to be crucial for regulation of the latent viral genome. PMID- 1312464 TI - Precursor protein translocation by the Escherichia coli translocase is directed by the protonmotive force. AB - The SecY/E protein of Escherichia coli was coreconstituted with the proton pump bacteriorhodopsin and cytochrome c oxidase yielding proteoliposomes capable of sustaining a protonmotive force (delta p) of defined polarity and composition. Proteoliposomes support the ATP- and SecA-dependent translocation of proOmpA which is stimulated by a delta p, inside acid and positive. delta p of opposite polarity, inside alkaline and negative, suppresses translocation while SecA mediated ATP hydrolysis continues unabated. delta psi and delta pH are equally effective in promoting or inhibiting translocation. Membrane-spanning translocation intermediates move backwards in the presence of a reversed delta p. These results support a model [Schiebel, E., Driessen, A.J.M., Hartl, F.-U. and Wickner, W. (1991) Cell, 64, 927-939] in which the delta p defines the direction of translocation after ATP hydrolysis has released proOmpA from its association with SecA. The polarity effect of the delta p challenges models involving delta p dependent membrane destabilization and provides further evidence for a role of the delta p as driving force in precursor protein translocation. PMID- 1312465 TI - Calcium channel beta subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. AB - Complementary DNAs encoding three novel and distinct beta subunits (CaB2a, CaB2b and CaB3) of the high voltage activated (L-type) calcium channel have been isolated from rabbit heart. Their deduced amino acid sequence is homologous to the beta subunit originally cloned from skeletal muscle (CaB1). CaB2a and CaB2b are splicing products of a common primary transcript (CaB2). Northern analysis and specific amplification of CaB2 and CaB3 specific cDNAs by polymerase chain reactions showed that CaB2 is predominantly expressed in heart, aorta and brain, whereas CaB3 is most abundant in brain but also present in aorta, trachea, lung, heart and skeletal muscle. A partial DNA sequence complementary to a third variant of the CaB2 gene, subtype CaB2c, has also been cloned from rabbit brain. Coexpression of CaB2a, CaB2b and CaB3 with alpha 1heart enhances not only the expression in the oocyte of the channel directed by the cardiac alpha 1 subunit alone, but also effects its macroscopic characteristics such as drug sensitivity and kinetics. These results together with the known alpha 1 subunit heterogeneity, suggest that different types of calcium currents may depend on channel subunit composition. PMID- 1312466 TI - Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. AB - The mechanistic relationship between the signalling for the TNF effects by the human p55 TNF receptor (hu-p55-TNF-R) and the formation of a soluble form of the receptor, which is inhibitory to these effects, was explored by examining the function of C-terminally truncated mutants of the receptor, expressed in rodent cells. The 'wild-type' receptor signalled for a cytocidal effect when cross linked with specific antibodies and exhibited spontaneous shedding. Shedding of the receptor was not affected by TNF but was markedly enhanced by 4 beta-phorbol 12-myristate-13-acetate (PMA). Receptor mutants with 53%, 83% and 96% C-terminal deletions could not signal for the cytocidal effect. Furthermore, they were found to associate with the endogenous rodent receptors, interfering with their signalling. Yet even the deletion of 96% of the intracellular domain did not abolish shedding of the receptor in response to PMA. These findings suggest that signalling and shedding of the p55 TNF-R are mechanistically distinct. PMID- 1312469 TI - Technetium-99m diethylene triamine penta-acetic acid and dimercaptosuccinic acid in the detection of a segmental branch stenosis of the renal artery by captopril renography. AB - We present a case in which a 39-year-old woman with correctable bilateral renovascular hypertension did not show abnormality during post-captopril technetium-99m dimercaptosuccinic acid (DMSA) study. Post-captopril 99mTc diethylene triamine penta-acetic acid (DTPA) scintigraphy revealed the adverse effect of a stenosis of the artery supplying the upper part of her left kidney but failed to uncover the existence of severe multiple narrowings of the right renal artery. After bilateral renovascular reconstructive surgery, the hypertension completely disappeared. This case illustrates that DTPA may be more efficacious than DMSA in the detection of segmental loss of renal function induced by angiotensin converting enzyme inhibition. PMID- 1312467 TI - Cyclin A is required at two points in the human cell cycle. AB - Cyclins play a fundamental role in regulating cell cycle events in all eukaryotic cells. The human cyclin A gene was identified as the site of integration of hepatitis B virus in a hepatocarcinoma cell line; in addition, cyclin A is associated with the E2F transcription factor in a complex which is dissociated by the E1A oncogene product. Such findings suggest that cyclin A is a target for oncogenic signals. We have now found that DNA synthesis and entry into mitosis are inhibited in human cells microinjected with anti-cyclin A antibodies at distinct times. Cyclin A binds both cdk2 and cdc2, giving two distinct cyclin A kinase activities, one appearing in S phase, the other in G2. These results suggest that cyclin A defines novel control points of the human cell cycle. PMID- 1312468 TI - Xenopus MAP kinase activator: identification and function as a key intermediate in the phosphorylation cascade. AB - MAP kinase is thought to play a pivotal role not only in the growth factor stimulated signalling pathway but also in the M phase phosphorylation cascade downstream of MPF. MAP kinase is fully active only when both tyrosine and threonine/serine residues are phosphorylated. We have now identified and purified a Xenopus MAP kinase activator from mature oocytes that is able to induce activation and phosphorylation on tyrosine and threonine/serine residues of an inactive form of Xenopus MAP kinase. The Xenopus MAP kinase activator itself is a 45 kDa phosphoprotein and is inactivated by protein phosphatase 2A treatment in vitro. Microinjection of the purified activator into immature oocytes results in immediate activation of MAP kinase. Further experiments using microinjection as well as cell free extracts have shown that Xenopus MAP kinase activator is an intermediate between MPF and MAP kinase. Thus, MAP kinase activator plays a key role in the phosphorylation cascade. PMID- 1312470 TI - Use of pertechnetate 99mTc for abdominal scanning in localising an ileal duplication cyst: case report and review of the literature. AB - A 10-year-old boy presented with periumbilical postprandial pain and some melena. Physical examination was normal. All investigations were negative except a pertechnetate 99mTc abdominal scan which showed a very large and horn-shaped focus of high activity in the right flank. An ileal duplication was resected. It was lined by antral gastric mucosa with a large ulcer. The patient was treated successfully. The abdominal pertechnetate scan is discussed. PMID- 1312471 TI - V beta repertoire in rats and implications for endogenous superantigens. AB - Endogenous superantigens of mice, encoded by mammary tumor virus proviral integrants, induce intrathymic deletion of entire T cell populations that express specific V beta gene products, a phenomenon proposed to be important in self tolerance and prevention of toxic responses to exogenous microbial superantigens. Evidence for the presence of V beta selecting/deleting endogenous superantigens in other species is lacking. We report here that rats do not exhibit endogenous superantigen-induced V beta clonal deletions despite their strong response to bacterial superantigens. These findings indicate that endogenous superantigens are not obligatory in V beta repertoire shaping. PMID- 1312472 TI - Gamma/delta T cell antigen receptors expressed on tumor-infiltrating lymphocytes from patients with solid tumors. AB - The expression of gamma/delta T cell antigen receptors (TcR) in T cell lines or clones derived from tumor-infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. gamma/delta TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non-disulfide-linked gamma/delta TcR using the 60-kDa gamma chain, whereas, the other expressed a disulfide-linked gamma/delta TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide-linked gamma/delta TcR, whereas, a T cell line derived from a patient with melanoma expressed a non-disulfide-linked gamma chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide- or non-disulfide-linked gamma/delta TcR. Northern analysis of RNA from certain of these clones revealed a full-length gamma chain transcript, whereas, the alpha or beta chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide- and non-disulfide-linked TIL T cell lines and clones expressed the delta TCS1 determinant. gamma/delta TcR+ cells in freshly prepared TIL from these patients were present in low proportions (less than 5%) and their delta TCS1/delta 1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide- and non-disulfide-linked gamma/delta TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non-disulfide-linked gamma/delta TcR using the 56-66-kDa gamma chain are frequently found on TIL-derived T cell lines and clones. These 56-66-kDa gamma chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors. PMID- 1312473 TI - Immunization with soluble simian virus 40 large T antigen induces a specific response of CD3+ CD4- CD8+ cytotoxic T lymphocytes in mice. AB - C57BL/6 (B6) mice (H-2b) were immunized with the large tumor antigen (T Ag) of simian virus 40 (SV40). Intraperitoneal or subcutaneous sensitization with soluble T Ag specifically primed cytotoxic lymphocyte precursors (CTLp). T Ag specific cytotoxic T lymphocytes (CTL) were detected in a cytotoxicity assay after specific in vitro restimulation of effector cell populations from mice immunized with 2-10 micrograms purified, soluble T Ag and boosted with an injection of 2 micrograms T Ag 2-4 weeks after priming. Cells used for in vitro restimulation and as targets in cytotoxicity assays were syngeneic (B6-derived) RBL5 lymphoma cells expressing SV40 T Ag after transfection with a T Ag-encoding expression vector. Effector cells of this response were H-2 class I-restricted CD3+ CD4-CD8+ CTL. The magnitude of the anti-T Ag CTL response of B6 mice stimulated by soluble virus protein was comparable to the anti-T Ag CTL response of SV40-infected B6 mice. Injections of denatured or native T Ag protein primed CTLp equally well, but immunization with an equal dose of antigen emulsified in incomplete Freund's adjuvants inefficiently stimulated CTLp. PMID- 1312474 TI - Expression of the murine interleukin 6 receptor in hepatoma cells: the intracytoplasmic domain is not required for interleukin 6 signal transduction. AB - This paper reports on cDNA coding for the 80-kDa murine IL6 receptor (mIL6R) that was cloned from a mouse liver cDNA library. Human hepatoma Hep3B cells transfected transiently or stably with an expression vector carrying the entire coding region for mIL6R become responsive to mouse IL6 (mIL6). We monitored response to the cytokine through the transcriptional activation of a co transfected IL6-inducible human C-reactive protein (CRP) promoter; response to mIL6 is lost upon treatment of the cells with increasing amounts of a monoclonal antibody to mIL6R. mIL6R mutants have been generated in the carboxy-terminal portion of the molecule. Their functional analysis in hepatoma cells shows that the intracytoplasmic domain of the receptor is not absolutely essential to IL6 signal transduction (i.e. CRP promoter activation), but that the last 40 amino acids contribute to maximal IL6 response in these cells. PMID- 1312475 TI - Immunoglobulin production in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells. AB - Immunodeficient C.B-17 scid/scid (SCID) mice were reconstituted with human peripheral blood mononuclear cells and analyzed for humoral immunity. The majority of adoptively transferred animals had serum levels of 1-4 mg/ml of human IgG 8-12 weeks after i.p. reconstitution with 20 x 10(6) PBMC, whereas the IgM and especially IgA concentrations were considerably lower. The half-lives of human IgG, IgM, and IgA in SCID mice were 12 days, 36, and 23 hours, respectively. Furthermore, IgA was rapidly secreted into bile indicating that the low IgA concentration was mainly caused by a high turnover rate. IgG subclass distribution in mouse serum was similar to that found in the donor serum. Irradiation with 3 Gy prior to adoptive transfer resulted in increased levels of human IgG early after reconstitution, whereas both IgM and IgA concentrations were impaired. A polyclonal serum Ig pattern was found 4 weeks after transfer of human cells later frequently followed by a predominance of oligoclonal bands. Unexpectedly, oligoclonal bands were also found using donors with a negative Epstein-Barr virus serology. Human cells were found to reside in the peritoneal cavity for several months. Within 2 weeks of reconstitution, human cells were also identified in lymphoid structures in the vicinity of the liver hilus with a later spread to other lymphoid organs. Homing of human cells to skin and gut was not seen. PMID- 1312476 TI - Biochemical analysis of the mouse mammary tumor virus long terminal repeat product. Evidence for the molecular structure of an endogenous superantigen. AB - Recent reports have shown that both exogenous and endogenous mouse mammary tumor viruses (MMTV) can encode superantigens. Transfection and transgenic studies have identified the open reading frame (ORF) present in the 3' long terminal repeat (LTR) as encoding superantigen function. In this study, we have used an in vitro translation system in an attempt to characterize the molecular nature of the protein encoded by the 3' ORF of Mtv-8. Using various constructs encoding full length and truncated versions of the ORF product, we report that the hydrophobic region close to the amino terminus of the 36-kDa protein can function as a transmembrane domain. Protease digestion experiments also demonstrate that the protein has a type-II transmembrane conformation with an extra-cytoplasmic carboxy terminus. Since this hydrophobic region is conserved between all known MMTV, we speculate that LTR ORF, including those proposed to encode the minor lymphocyte stimulatory antigens, are also capable of encoding type-II transmembrane glycoproteins. The polymorphism between MMTV LTR ORF products, which correlates with deletion phenotypes, is predominantly in the carboxy terminal extracellular region, consistent with a major role in interaction with the T cell receptor. PMID- 1312477 TI - Epidemiology and aetiology of acute bronchiolitis in Hong Kong infants. AB - The epidemiological, clinical and virological features of 1220 children with acute bronchiolitis admitted to the Prince of Wales Hospital, Hong Kong, from 1985 to 1988 are reported. They accounted for 6.6% of total paediatric admissions and provided a case incidence of bronchiolitis requiring admission to hospital of approximately 21 per 1000 children 0-24 months of age. The clinical course and outcome was in general benign. The average hospital stay was 5 days and there were no deaths. Ten per cent of patients were repeatedly admitted to hospital with recurrent wheezing after discharge. Two infants developed bronchiolitis obliterans. Respiratory syncytial virus (RSV) was shown by direct immunofluorescence, virus culture and serology to be the commonest cause of acute bronchiolitis in Hong Kong. Other aetiological agents included parainfluenza and influenza viruses, adenoviruses, and Mycoplasma pneumoniae. In contrast to western countries, a seasonal variation of bronchiolitis was found with a peak incidence in the summer months. The significance of these observations is discussed. PMID- 1312478 TI - A 2-year survey of the prevalence of enteric viral infections in children compared with contamination in locally-harvested oysters. AB - We studied, for two years, the prevalence of indigenous human enteric viruses in wild oysters gathered each month from the bottom of Mikawa Bay, Aichi Prefecture, Japan. Viruses were detected periodically in 9 out of 54 oyster pools prepared by the acid or polyethylene glycol precipitation method although all these 9 pools met current national bacteriological safety standards. Since most of the serotypes of the enteric viruses detected in the oysters were identical with those of viruses isolated from sick children living in the area, it is suggested that contamination of enteric viruses in the oysters would depend on the prevalence of enteric viral infections in the local inhabitants. PMID- 1312479 TI - Antibody-capture enzyme-linked immunosorbent assays that use enzyme-labelled antigen for detection of virus-specific immunoglobulin M, A and G in patients with varicella or herpes zoster. AB - Antibody-capture enzyme-linked immunosorbent assays (AC-ELISA) which use enzyme labelled antigen were developed for detection of varicella-zoster virus-(VZV) specific IgM, IgA and IgG antibody in patients with varicella or herpes zoster and in sera from healthy individuals. All 18 patients with varicella developed a VZV-IgM and a VZV-IgG response, 17 also a VZV-IgA response. In contrast, all 19 patients with herpes zoster were shown to be positive for VZV-IgA whereas only 13 of these reacted positively for VZV-IgM. A VZV-IgM response was detected in only two sera from 100 healthy individuals and an IgA response in only one. The presence of virus-specific IgA and IgG in the cerebrospinal fluid as determined by AC-ELISA was a useful indicator of VZV infection of the central nervous system. By AC-ELISA, VZV-IgG was detected predominantly in sera from patients with acute or recent VZV infection. Only 14 sera from 100 healthy individuals were positive for VZV-IgG by AC-ELISA, whereas all were positive by an indirect ELISA. These results indicate that AC-ELISA's may be useful assays for determination for acute or recurrent VZV infection, but are not suitable for determination of past infection with this virus. PMID- 1312481 TI - Evolution of Ig- and T-cell receptor gene configuration in a Ph1+ hybrid leukemia patient. AB - In a longitudinal study of a 32-year-old male with Ph1+ hybrid leukemia we have followed the immunophenotype and configuration of Ig- and TCR genes during the course of different chemotherapy regimens directed first against the myeloid and later against the lymphoid components of the disease. We identified changes in all parameters, interpretable as an evolution of the malignant clone resulting in a leukemic switch towards a more lymphoid character. Thus, while the expression of the myeloid antigens CD13 and CD33 decreased, that of CD10 (CALLA) and CD20 (B1) increased. Moreover, while the configuration of the Ig heavy and light chain lambda genes remained constant during the whole period of treatment, that of the Ig light chain kappa gene and TCR beta gene displayed extensive rearrangements after initiation of ALL therapy. Since this patient represents a de novo acute leukemia as evaluated by location of the translocation-breakpoint on chromosome 22, our data clearly indicate that Ig- and TCR gene rearrangements might prove a valuable addition in monitoring Ph1+ hybrid leukemias, providing guidelines for optimizing chemotherapy. PMID- 1312480 TI - Rotavirus detection by dot blot hybridization assay using a non-radioactive synthetic oligodeoxynucleotide probe. AB - A synthetic oligodeoxynucleotide of 40 nucleotides corresponding to nucleotides 33-72 of the gene coding for the viral protein VP7 of rotavirus, was used as a nucleic acid probe to develop a non-radioactive hybridization method for rotavirus detection. The probe was labelled at the 3' end with biotin-7-dATP. The sensitivity and specificity of the dot blot hybridization assay for rotavirus detection was evaluated with 303 stool specimens. The results indicate that the hybridization assay has a higher sensitivity than both PAGE and EIA. Among the rotavirus strains tested 37 different electropherotypes were found. The results suggest that rotavirus diagnosis by dot hybridization using a non-radioactive probe may become routine laboratory procedure because it is simple, highly specific and very sensitive. PMID- 1312482 TI - Fluorescence study on cardiac glycoside binding to the Na,K-pump. Ouabain binding is associated with movement of electrical charge. AB - Recently we have presented evidence that the fluorescence probe RH 421 can be used to detect binding and release of ions at the extracellular face of the pump since these processes are associated with translocation of electrical charge. Applying this method to experiments with cardiac glycosides we found that: (1) ouabain induced fluorescence changes of the electrochromic dye, RH 421, were caused by the change of charges bound to the enzyme; (2) independent of the sodium concentration, the final fluorescence amplitude indicated that approximately 2 Na+ ions were bound to the pump; (3) the sodium release to the extracellular side involved two distinct electrogenic steps; (4) the kinetics of inhibition depended on the Na(+)-concentration. Experiments with hydrophobic ions indicated that the kinetics of ouabain binding to the Na-ATPase is voltage dependent; and (5) the applied technique is a convenient tool to characterize binding of cardiac glycosides to the Na,K-pump. PMID- 1312483 TI - Action of Escherichia coli and human 5'----3' exonuclease functions at incised apurinic/apyrimidinic sites in DNA. AB - The 5'----3' exonuclease activity of E. coli DNA polymerase I and a related enzyme activity in mammalian cell nuclei, DNase IV, are unable to catalyse the excision of free deoxyribose-phosphate from apurinic/apyrimidinic (AP) sites incised by an AP endonuclease. Instead, the sugar phosphate residue is slowly released as part of a short oligonucleotide. These products have been characterised as dimers and trimers by comparison of their retention time on reverse-phase HPLC with reference compounds prepared by acid depurination of a dinucleotide, trinucleotide and tetranucleotide containing a 5'-terminal dAMP residue. The similar mode of action of these enzymes at 5'-incised AP sites provides an explanation for the minority of repair patches larger than one nucleotide observed when AP sites are repaired by E. coli and mammalian cell extracts in vitro and strengthens the functional analogy between the two activities. PMID- 1312485 TI - Inhibition of neutrophil superoxide production by human plasma alpha 1 antitrypsin. AB - We report here that human plasma alpha 1-antitrypsin (alpha 1-AT) inhibited human neutrophil O2.- release elicited by a variety of stimulants. In comparison, the inhibitory capacities of two serine protease inhibitors, L-1-tosylamide 2 phenylethyl chloromethyl ketone (TPCK) and soybean trypsin inhibitor (SBTI), and the human recombinant alpha 1-AT mutant, alpha 1-AT-Arg358 were in the order: alpha 1-AT = TPCK much greater than alpha 1-AT-Arg358 greater than SBTI when cells were stimulated with concanavalin A plus cytochalasin E. These data suggest that, in human inflammatory fluids containing relatively high concentrations of alpha 1-AT (such as rheumatoid arthritis synovial fluid), (i) alpha 1-AT may down regulate the inflammatory process by inhibiting the neutrophil respiratory burst and (ii) serpin oxidation by neutrophil-released reactive oxygen species is unlikely to occur. PMID- 1312484 TI - Identification and characterization of urokinase receptors in natural killer cells and T-cell-derived lymphokine activated killer cells. AB - Fluorescence-activated cell scanning analysis of human blood cells revealed novel urokinase receptors in large granular lymphocytes and a small subset of T-cells (CD3+). Culturing of T-cells with interleukin-2 to generate CD3+ lymphokine activated killer cells caused a large increase in urokinase binding, suggesting that the urokinase receptor is an activation antigen. The receptor in lymphocytes was similar to that in monocytes with regard to size, affinity and ligand specificity, but did not mediate degradation of urokinase-inhibitor complexes. It is suggested that lymphocyte-bound pro-urokinase is activated, e.g. by the human T-cell-specific serine proteinase, HuTSP-1, and thereby starts a cascade of plasminogen activation important for extravasation of the cells. PMID- 1312486 TI - Detection of elsamicin-DNA binding specificity by restriction enzyme cleavage. AB - The sequence specificity of elsamicin A, an anti-tumour antibiotic, binding to DNA was elucidated considering the inhibition of the rate of digestion of linearised pBR322 DNA by AatII, ClaI, EcoRI, HindIII and NruI restriction enzymes. Elsamicin A inhibits the rate of digestion by NruI (recognition sequence TCG/CGA) to a greater extent than it does for the other enzymes, thus evidencing the sequence-selective binding of elsamicin to CGC regions in DNA. Our results also show the important role of the neighbouring sequences in the elsamicin A-DNA interactions and their effects on the cleavage by restriction enzymes. PMID- 1312487 TI - Identification of a component separated on Mono Q purification of Escherichia coli RNA polymerase as an NTPase. AB - Standard preparations of Escherichia coli RNA polymerase (RNAP) contain NTPase activity. High-performance anion-exchange chromatography on Mono Q has recently been used by Hager et al. [1990, Biochemistry 29, 7890-7894] to fractionate RNAP into holoenzyme (alpha 2 beta beta' sigma) and core (alpha 2 beta beta') forms, plus other protein components. We found that one of these components, of protomer size slightly larger than the sigma 70 subunit, has NTPase activity; it is efficiently separated on Mono Q, leaving transcriptionally active holoenzyme and core apparently free of NTPase activity. Because of the similarity in size with sigma 70, the NTPase component may escape detection by routine gel electrophoresis. PMID- 1312488 TI - The use of the amplifiable high-expression vector pEE14 to study the interactions of autoantibodies with recombinant human thyrotrophin receptor. AB - In order to produce significant quantities of the human thyrotrophin (TSH) receptor we have investigated the use of two eukaryotic high expression systems. DNA encoding the receptor was obtained by the polymerase chain reaction (PCR) applied to thyroid cDNA. Receptor DNA was inserted into the baculovirus system; despite high mRNA levels there was little or no demonstrable protein production. However, using a novel amplifiable glutamine synthetase system, clones of transfected Chinese hamster ovary (CHO) cells expressed a high affinity TSH receptor (KD 0.225 +/- 0.046 nM, Bmax 20,000-45,000 sites/cell for individual clones). This was coupled to adenylate cyclase as measured by a TSH-stimulatable increase in extracellular cyclic AMP (cAMP), a detectable response being noted at 1 microU/ml TSH with half-maximal at around 25-50 microU/ml. The high expression allowed detection of both TSH binding inhibition and adenylate cyclase stimulation by autoantibodies in unfractionated sera from patients with Graves' disease. PMID- 1312489 TI - TPA decreases 1,25(OH)2D3 binding and calbindin D-28K in renal (MDBK) cells. AB - The effect of the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) on vitamin D receptors (VDRs) was studied in MDBK cells, a normal bovine renal epithelial cell line. 24 h treatment of MDBK cells with TPA resulted in down regulation of VDR number, with no change in the binding affinity for 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) or approximate molecular weight determined by fast protein liquid chromatography (FPLC). TPA treatment also reduced the level of calbindin D-28K, a vitamin D-dependent renal protein. 4 alpha-Phorbol 12,13 didecanoate (4 alpha-PDD), an inactive phorbol ester, did not affect either 1,25(OH)2D3 binding or calbindin D-28K levels. TPA elicited a significant decrease in membrane-associated protein kinase C (PKC) activity which coincided with the reduction in VDR number and calbindin D-28K. These data support a link between TPA, PKC activity and vitamin D actions in kidney. PMID- 1312490 TI - Osmolytes improve the reconstitution of luteinizing hormone/human chorionic gonadotropin receptors into proteoliposomes. AB - Rat ovarian membrane luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor was reconstituted into proteoliposomes. The ability of sodium cholate to extract and reconstitute hCG binding activity was dependent on the protein/detergent ratio. Trypsinization of the LH/hCG receptor containing proteoliposomes indicated that approximately 57% of hCG binding sites were oriented extravesicularly. The presence of 20% glycerol or other osmolytes during reconstitution increased the accessibility of LH/hCG receptors but not the activity of adenylate cyclase in proteoliposomes. This beneficial effect was independent of any specific detergent or its presence during detergent solubilization of proteins. Dynamic properties of membranes were monitored by electron spin resonance of 16-, 12-, and 5-doxyl stearic acid. Reconstituted proteoliposomes contain less ordered membrane lipids than do native membranes. Addition of glycerol before reconstitution increased the order of lipid bilayer and shifted it to the physical state of the native membrane. These findings are consistent with the hypothesis that a rise in membrane ordering increases the accessibility of membrane-bound LH/hCG receptors. PMID- 1312491 TI - In vivo proliferation of rat vascular smooth muscle in relation to diabetes mellitus insulin-like growth factor I and insulin. AB - The roles of diabetes mellitus, insulin-like growth factor I and insulin in vascular smooth muscle proliferation in vivo were studied. Proliferation was induced by endothelial injury (balloon catheterization) of rat aorta, and was measured as 3H-thymidine incorporation into DNA. Levels of insulin-like growth factor I mRNA and insulin-like growth factor I receptor mRNA were measured with a solution hybridization assay. The increase in DNA synthesis was most pronounced 2 days after injury in both normal and diabetic rats and declined thereafter, but DNA synthesis in aortas from diabetic rats was lower throughout the time period studied. Levels of insulin-like growth factor I mRNA and the receptor mRNA were both increased in balloon catheterized aortas, and time-course studies showed an increase in receptor mRNA prior to the increase in insulin-like growth factor I mRNA. Diabetic rats were treated with equimolar concentrations of insulin (35 nmol/day) or insulin-like growth factor I (31 nmol/day) for 5 days. Insulin-like growth factor I increased DNA synthesis in injured aortas 2 days after injury without improving blood glucose, whereas the effect of insulin was associated with a decrease in blood glucose levels. In conclusion, vascular smooth muscle proliferation is impaired by diabetes and stimulated by insulin treatment. Insulin-like growth factor I infusion stimulates vascular smooth muscle proliferation without affecting blood glucose, and gene expressions of insulin like growth factor I and its receptor are increased in proliferating vascular smooth muscle, indicating that insulin-like growth factor I and involved in vascular smooth muscle proliferation in vivo. PMID- 1312492 TI - Effect of phospholipase treatment on insulin receptor signal transduction. AB - To study the role of membrane lipids in signal transduction by the insulin receptor, we have studied the effect of phospholipase C (Clostridium perfringens) and a phosphatidylinositol-specific phospholipase (Staphylococcus aureus) on insulin binding, a function of the alpha-subunit, and tyrosine kinase activity, a function of the beta-subunit in IM-9 lymphocytes and NIH 3T3 fibroblasts transfected with the human insulin receptor. Treatment of the cells with phospholipase C at concentrations up to 3.4 U/ml did not affect specific insulin binding, but reduced insulin-stimulated receptor phosphorylation by 50%. This effect of phospholipase C was observed within 10 min of treatment and occurred with no change in the basal level of phosphorylation. Pre-treatment of cells with insulin for 5 min prior to enzyme addition prevented any change in kinase activity. Insulin-stimulated phosphorylation of pp 185, the presumed endogenous substrate for the insulin receptor kinase, was also reduced following phospholipase C treatment, with an almost complete loss of insulin stimulation after exposure of cells to enzyme at concentrations as low as 0.6 U/ml. In contrast to these effects of phospholipase C on intact cells, receptor autophosphorylation was not affected in insulin receptors purified on wheat germ agglutinin-agarose from phospholipase C treated cells. Likewise, the phospholipase C effect was reduced by the addition of phosphatidylcholine, but not by the addition of the protease inhibitors, aprotinin and phenylmethylsulfonyl fluoride, to the incubation indicating its dependence on phospholipid hydrolysis. Treatment of cells with the phosphatidylinositol specific phospholipase C did not affect any of the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312493 TI - Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver. AB - The impact of (pancreatic) islet amyloid polypeptide on glucose metabolism and insulin sensitivity was examined in isolated rat livers perfused in a non recirculating system. Continuous infusion of 10(-7) mol/l islet amyloid polypeptide affected neither basal nor glucagon (10(-9) mol/l)-stimulated glucose output by livers from fed rats, but it did increase the hepatic cyclic AMP release within 44 min (7.91 +/- 12.07 vs control: 0.07 +/- 0.03 pmol x 100 g body weight-1). The effect of the peptide on the ability of insulin to inhibit glucagon-induced hepatic glycogenolysis was measured in three experimental groups (n = 6). As expected glucagon (7 x 10(-11) mol/l) increased integral hepatic glucose release within 84 min (763.4 +/- 161.7 vs -25.7 +/- 73.2 mumol x 100 g body weight-1 in the control group, p less than 0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2 +/- 180.0 mumol x 100 g body weight-1, p less than 0.01). Simultaneous infusion of 10(-7) mol/l islet amyloid polypeptide however, was not able to reverse insulin-dependent inhibition of glucagon-stimulated hepatic glucose output (370.0 +/- 102.5 mumol x 100 g body weight-1, NS) or to enhance lactate-induced gluconeogenesis of livers from 24 h fasted rats (n = 8). The glucose production stimulated by 10(-9) mol/l glucagon was slightly greater in islet amyloid polypeptide-pre-treated livers than in a control group without addition of islet amyloid polypeptide (5 min: 3.60 +/- 3.36 vs 1.67 +/- 1.28 mumol.min-1 x 100 g body weight-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312494 TI - Autoimmune diabetes and the germ theory of disease. PMID- 1312495 TI - [Granular cell tumor misdiagnosed as scirrhous breast cancer]. AB - The granular cell tumour, a rare benign tumour of the breast, is described. Its appearance is highly suspicious for malignancy on clinical, mammographic and ultrasonographic investigations. Only histological examination of the tumour, which mimics a scirrhous carcinoma, leads to the definite diagnosis. PMID- 1312496 TI - [Postmenopausal virilization in thecosis of the ovaries]. AB - We describe the case of a 74-year-old woman with a fifteen-year old history of virilism and with a Type-II-diabetes mellitus treated with insulin. After the removal of the ovaries, the formerly elevated serum-testosterone levels normalised and the signs of virilism gradually abated. The histological finding of stromal thecosis in the ovaries is discussed in relation to hyperinsulinaemia and other potential stimuli for ovarian stromal hyperplasia. PMID- 1312498 TI - New tools for the physical and genetic mapping of Lactococcus strains. AB - Tools for the genetic and physical analysis of the Lactococcus lactis subsp. lactis genome were developed. Plasmid pRC1 does not replicate in Gram+ bacteria; it contains unique ApaI, NotI and SmaI restriction sites and an erythromycin resistance (ErR) encoding gene, ermAM, functional in L. lactis subsp. lactis. When a chromosomal L. lactis subsp. lactis DNA fragment was cloned into this vector, the resulting plasmid became integrated, after transformation, into the bacterial chromosome by homologous recombination in a Campbell-like manner. The integration lead to the generation of new rare restriction sites near to the host fragment. This procedure allows precise mapping of cloned genes onto the chromosomal restriction map. The mapping of the his operon of L. lactis subsp. lactis provides an illustration. The cloning into pRC1 of an IS element able to transpose into the chromosome of the target cell, gave rise to an integration plasmid able to insert randomly rare restriction sites onto the bacterial chromosome. The L. lactis IS element, ISS1RS, was cloned into pRC1, yielding pRL1. Pulsed-field gel electrophoresis analysis of ErR clones obtained after transformation with pRL1, showed that this plasmid was stably integrated at a number of different sites in the L. lactis subsp. lactis chromosome, via transposition. Plasmids pRC1 and pRL1 can greatly facilitate the construction of the physical and genetic map of the chromosome of lactococcal strains. PMID- 1312497 TI - Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. AB - An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXR alpha, beta, and gamma). They are closely related to each other in their DNA- and ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXR alpha. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXR alpha, beta, and gamma. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology. PMID- 1312499 TI - Complete nucleotide sequence of Tn1721: gene organization and a novel gene product with features of a chemotaxis protein. AB - The complete 11,139-nucleotide sequence of transposon Tn1721 has been determined. It contains three 38-bp inverted repeats, and (in this order) a new orfI, a resolution site (res), genes encoding resolvase (tnpR), transposase (tnpA), tetracycline-resistance (TcR) repressor (tetR), TcR (tetA) and a truncated transposase gene (tnpA'). The modulator origin of Tn1721 from at least three separate sources is supported by the distinctive codon usages of orfI, tnpR/tnpA and tetR/tetA, and by sequence similarities with Tn501 (tnpR/tnpA) and RP1 (tetR/tetA). The ORFI-encoded 56-kDa polypeptide exhibits features of a methyl accepting chemotaxis protein (MCP) with a conserved signal domain and a potential transmembrane domain; this polypeptide cross-reacts with anti-MCP antiserum. Like chemotaxis genes, orfI is transcribed from a sigma 28-like promoter. The overexpressed orfI gene product interferes with MCP-dependent chemotaxis suggesting that it completes for soluble transducer protein(s) in the cell. The potential selective advantage of this novel transposon-borne gene is discussed. PMID- 1312500 TI - Physical mapping of the Saccharomyces cerevisiae Ap4A phosphorylase I-encoding gene by the Achilles' cleavage method. AB - LacI-mediated Achilles' cleavage (AC) is a method for selective fragmentation of chromosomes at special lac operator sites introduced by gene targeting methods [Koob and Szybalski, Science 250 (1990) 271-273]. The Saccharomyces cerevisiae APA1 gene, coding for diadenosine 5', 5"'-P1, P4-tetraphosphate phosphorylase I, has previously been shown to be located on chromosome III [Kaushal et al., Gene 95 (1990) 79-84]. We have now used the AC method to map APA1 gene to a site 44 kb from the left terminus of the chromosome, between the HIS4 and HML genes. This location was confirmed by the comparison of restriction maps of the APA1 gene region to published restriction maps of chromosome III. PMID- 1312501 TI - TnblaM: a transposon for directly tagging bacterial genes encoding cell envelope and secreted proteins. AB - A transposon, TnblaM, designed for the direct selection of bacterial mutants with insertions in genes encoding cell envelope and secreted proteins, was constructed and subcloned into plasmid and bacteriophage lambda delivery vectors. TnblaM is a spectinomycin-resistant derivative of Tn5 with an unexpressed open reading frame encoding mature beta-lactamase (BlaM) at its left end. Therefore, when it inserts into genes in the correct orientation and reading frame, gene fusions encoding hybrid proteins are generated. By introducing TnblaM into bacterial cells and selecting ampicillin-resistant (ApR) colonies, the subset of isolates producing extracytoplasmic BlaM, and hence containing TnblaM inserted in genes encoding secreted proteins and cell envelope proteins, can be directly selected. TnblaM, like TnphoA, can therefore be used to preferentially mutagenise genes encoding extracytoplasmic proteins, but it has the advantage over TnphoA that the desired mutants can be isolated by direct selection (as ApR colonies) rather than by phenotypic screening. Isolates in which TnblaM occupies sites in the chromosome from which it can transpose at high frequency are readily identifiable, and constitute TnblaM donors, with which to simply and efficiently generate rare types of insertion mutants. Moreover, the ApR selection that is used with TnblaM can be fine-tuned to obtain blaM fusions to poorly or well-expressed genes. PMID- 1312502 TI - A two-component T7 system for the overexpression of genes in Pseudomonas aeruginosa. AB - A two-component T7 expression system was developed for efficient expression of genes in the nonenteric bacterium, Pseudomonas aeruginosa. The first component of the expression system is a bacteriophage-based transposable element that contains a lacUV5/lacIq-regulated T7 RNA polymerase gene and a selectable antibiotic resistance determinant. This element, designated miniD-180, was stably integrated into the P. aeruginosa PAO1 chromosome. The second component of this system includes several improved broad-host-range expression vectors containing the T7 gene 10 promoter and multiple cloning site (MCS). These vectors (pEB8, pEB11, and pEB12) contain transcriptional terminators (T1(4)) upstream from the T7 promoter, and T7 terminators downstream from the MCS. Because the T7 promoter is somewhat leaky in these vectors, pEB14 was constructed to decrease transcription of target genes by basal levels of T7 RNA polymerase. This vector contains a core sequence of the lac operator located 19 bp downstream from the transcriptional start point of the T7 promoter, thereby providing a dually regulated system. The utility of this system was demonstrated by placing a promoterless chloramphenicol acetyltransferase (CAT) cassette under control of the T7 promoter and monitoring the isopropyl-beta-D-thiogalactopyranoside-dependent accumulation of CAT in cell free extracts of P. aeruginosa. We observed up to nearly a 60-fold increase in CAT levels 4 h post-induction, at which time this polypeptide represented up to 20% of the total soluble protein. PMID- 1312503 TI - Localization of the exonuclease and polymerase domains of Bacillus subtilis DNA polymerase III. AB - Structural gene mutants were cloned and exploited to identify the major catalytic domains of Bacillus subtilis DNA polymerase III (BsPolIII), a 162.4-kDa [1437 amino acids (aa)] polymerase: 3'-5' exonuclease (Exo) required for replicative DNA synthesis. Analysis of the sequence, mutagenicity, and catalytic behavior of natural and site-directed point mutants of BsPolIII unequivocally located the domain involved in exonuclease catalysis within a 155-aa residue segment displaying homology with the Exo domain of Escherichia coli DNA polymerase I. Sequence analysis of four structural gene mutations which specifically alter then enzyme's reactivity to the inhibitory dGTP analog, 6-(p hydroxyphenylhydrazino)uracil, and the inhibitory arabinonucleotide, araCTP, defined a domain (Pol) involved in dNTP binding. The Pol domain was in the C terminal fourth of the enzyme within a 98-aa segment spanning aa 1175-1273. The primary structure of the domain was unique, displaying no obvious conservation in any other DNA polymerase, including the distantly related PolIIIs of the Gram- organisms, E. coli and Salmonella typhimurium. PMID- 1312504 TI - [Clinical significance of papillomaviruses in gynecology]. PMID- 1312505 TI - The influence of different sera on the in vitro immobilisation of Percoll purified Treponema pallidum, Nichols strain. AB - OBJECTIVES: Investigation of sera, especially rabbit serum, in preventing in vitro immobilisation of Percoll purified T. pallidum. MATERIALS AND METHODS: The immobilisation of Percoll purified T. pallidum (Nichols) was studied after pre incubations with basal reduced medium (BRM), heat-inactivated serum of seven different species of animals, heat-inactivated normal human serum (NHS) and rabbit sera containing a different level of antitreponemal antibodies. Also increasing percentages of heat-inactivated normal rabbit serum (NRS) were studied. RESULTS: The rapid immobilisation of purified treponemes by NHS is delayed by pre-incubation with NRS in a dose-dependent manner. The treponemes from 5-day infections were immobilised significantly more slowly than treponemes from 7- and 8-day infections. Compared with NRS, pre-incubations with a high titred, low-titred and "autologous" serum resulted in significantly more rapid immobilisation of the treponemes. With most other animal sera resistance to immobilisation was slight compared with that produced by NRS. Immunofluorescent studies revealed that the treponemes were covered with a layer of the human third complement factor (C3b), within an hour of incubation. With two sequential pre incubations, a delay of the immobilisation was only noted in those test mixtures in which NRS had been present in both preincubations. CONCLUSION: Rabbit serum delays the rapid in vitro immobilisation of Percoll purified treponemes by normal human serum. There was no evidence that this was caused by preventing access of antibodies (in vivo as well as in vitro) to, or preventing the activation of complement on, the treponemal surface. The evidence points to a mechanism in the fluid phase, suggesting participation of a third factor in the immobilisation process, for instance an enzyme, which can be partially inhibited by rabbit serum component(s). PMID- 1312506 TI - Treatment of vaginal candidosis: a comparative study of the efficacy and acceptability of itraconazole and clotrimazole. AB - OBJECTIVE: To compare the clinical and mycological efficacy and patient acceptability of the oral antifungal itraconazole with vaginal clotrimazole in the treatment of vaginal candidosis. DESIGN: A multicentre, single-blind, randomised, parallel group comparison of itraconazole and clotrimazole. SETTING: 17 Genito Urinary Medicine clinics in UK hospitals. SUBJECTS: Women with symptomatic, culture positive vaginal candidosis. METHODS: Patients were randomly allocated 2 x 100 mg itraconazole capsules to be taken twice in a 24 hour period, or a 500 mg clotrimazole vaginal tablet. Clinical and mycological assessments were made at entry and after approximately seven and 35 days. OUTCOME MEASURES: Cure rate was defined in terms of mycological results, and patients were questioned on their opinion of treatment. RESULTS: Of 214 patients, 109 received itraconazole and 105 clotrimazole with similar improvement in clinical signs and symptoms. Mycological cure rates one week after treatment were obtained in 72 of 97 patients (74%) in the itraconazole group and 64 of 89 patients (72%) in the clotrimazole group. Identical mycological cure rates six weeks after treatment were obtained with 40 of 79 patients (51%) receiving itraconazole and 39 of 78 patients (50%) receiving clotrimazole. CONCLUSION: Clotrimazole and itraconazole were found to be equally effective. A majority of patients receiving the latter preferred it to previous treatments. PMID- 1312507 TI - Laboratory techniques in the investigation of human papillomavirus infection. PMID- 1312508 TI - Cytomegalovirus and AIDS. PMID- 1312509 TI - G proteins in T cell signal transduction. AB - This review summarises recent data on G protein implication in receptor signalling in T cells. The data show that PPI-specific PLC in T cell membranes is under G protein control. Some evidence indicates that a G protein couples PLC to TCR. Differences are revealed between the effects induced by direct G protein activators, such as GTP gamma S or AlF4-, and TCR ligands, which imply that TCR ligands may trigger some G-protein-independent signals. An analysis of the conflicting results on the action of PTX and CTX, one of the main tools in studying G proteins, has shown that the toxins produce both G protein-dependent and independent effects. The G protein which couples PLC to TCR appears insensitive to both PTX and CTX. Some findings suggest G protein involvement in signalling induced by interleukins; however, in this case the effector molecules implicate often remain unknown. Scarce data on G protein involvement in signalling from differentiation antigens, on direct G protein regulation of ion channels, and on identification of G proteins in T cells, are also discussed. PMID- 1312510 TI - The immune response against foot-and-mouth disease virus: influence of the T lymphocyte growth factors IL-1 and IL-2 on the murine humoral response in vivo. AB - Recombinant and pure "natural" IL-1 and IL-2 were compared with the muramyl dipeptide (MDP) component of Freund's adjuvant for their capacity to enhance the humoral immune response against foot-and-mouth disease (FMD) virus antigen. Using a dose of this antigen which alone did not give a detectable immune response, anti-FMD virus antibody was measured at 14 and 28 days post-vaccination. Although IL-1 could enhance the response against the virus antigen, in particular when administered 24 h before the vaccine, this was not as strong as that obtained when MDP was adjuvant. In contrast, IL-2 was at least as efficient as MDP when applied concomitantly with the antigen. If the IL-2 treatment preceded the vaccination by 24 h, a diminution in the magnitude of the response was seen; however, this was countered by the fact that 10 times less IL-2 was required, compared with concomitant cytokine/vaccine administration, in order to have the maximum effect. When both IL-1 and IL-2 were used together, an even greater enhancement of the immune response against FMD virus antigen was observed, but only when given concomitantly with the antigen. These results demonstrate the relevance of T lymphocyte growth factors to the immune response against FMD virus, and how current immunological and biotechnological knowledge could be applied to the improvement of adjuvant systems in a chemically and biologically defined manner. PMID- 1312511 TI - Signal transduction during antibody-dependent cellular cytotoxicity mediated by U937 cells. AB - Stimulation of the human promonocytic cell line U937 with antibody-coated chicken red blood cells (Ab-CRBC), leads to inositol phosphate (IP) release in the effector cells. Neomycin (5 x 10(-4) M) completely inhibits activation of phosphoinositide breakdown, while ADCC is suppressed in a dose-dependent manner. Bordetella pertussis toxin (PT) (0.5 micrograms/ml), entirely inhibits IP release, while ADCC activity is markedly suppressed. The PKC inhibitors H-7 and propranolol also suppress ADCC. HA-1004, which has far lower PKC inhibitory activity than H-7, has a minimal effect on ADCC. The calmodulin antagonists W-7 and TFP are strongly inhibitory. These results indicate that stimulation of U937 cells for ADCC is associated to an increase in IP levels, which may provide positive transduction signals for the activation of this lytic mechanism. PMID- 1312512 TI - Effect of angiotensin II on renin production by rat adrenal glomerulosa cells in culture. AB - Angiotensin II (Ang II) inhibits renin secretion and production from the kidney, but the effect of Ang II on adrenal renin is not clear. Nephrectomy, via elevated plasma adrenocorticotropic hormone (ACTH) and potassium, is a strong stimulator of adrenal renin production in the rat. This stimulation is inhibited by the infusion of Ang II, suggesting a negative feedback between Ang II and adrenal renin. In the present study, we examined the effect of Ang II on adrenal renin using a primary culture of rat glomerulosa cells. Cells were exposed to ACTH (10( 11) M), high potassium (8 and 12 mM), db-cyclic AMP (db-cAMP), (10(-3) M), or Ang II (10(-11) to 10(-5) M) for 24 hours, and active renin and inactive renin were measured. Active renin was predominant in the cells, whereas inactive renin predominated in the medium. Ang II stimulated renin production in a dose dependent fashion (cell-active renin, 1.21 +/- 0.20 to 2.39 +/- 0.16; medium inactive renin, 2.59 +/- 0.40 to 6.14 +/- 0.49 ng Ang I/10(6) cells). Both ACTH and db-cAMP significantly stimulated active renin in the cells (ACTH, 1.73 +/- 0.14 to 9.44 +/- 0.98; db-cAMP, 1.45 +/- 0.16 to 3.96 +/- 0.71 ng Ang I/10(6) cells) and inactive renin in the medium (ACTH, 4.98 +/- 0.38 to 43.7 +/- 5.63; db cAMP, 3.80 +/- 0.32 to 33.55 +/- 5.62 ng Ang I/10(6) cells). The addition of Ang II (10(-7) M) blunted the stimulation of renin production by both ACTH and db cAMP by 60%. High potassium-stimulated renin production was not inhibited by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312513 TI - Inhibition by converting enzyme inhibitors of pig kidney aminopeptidase P. AB - Several inhibitors of angiotensin converting enzyme were also found to inhibit aminopeptidase P, whereas inhibitors of other mammalian aminopeptidases were ineffective. Aminopeptidase P purified from pig kidney cortex was found to contain one atom of zinc per polypeptide chain, confirming its metalloenzyme nature. The concentrations of converting enzyme inhibitors required to cause 50% inhibition (I50) of aminopeptidase P were in the low micromolar range. The most potent converting enzyme inhibitors toward aminopeptidase P were the carboxylalkyl compounds, cilazaprilat, enalaprilat, and ramiprilat (I50 values of 3-12 microM). The sulfhydryl compounds captopril (I50 110 microM) and YS980 (I50 20 microM) were slightly less potent at inhibiting aminopeptidase P. In contrast, the carboxylalkyl compounds benazeprilat, lisinopril, and pentoprilat; the sulfhydryl compound rentiapril; and the phosphoryl compounds ceranopril and fosinoprilat had no inhibitory effect against aminopeptidase P. This compares with I50 values in the 1-6 nM range for these inhibitors with angiotensin converting enzyme. Inhibition of aminopeptidase P may account for some of the effects or side effects noted with the clinical use of converting enzyme inhibitors. These results may provide the basis for the design of more selective inhibitors of angiotensin converting enzyme or mixed inhibitors of aminopeptidase P and angiotensin converting enzyme, or both. PMID- 1312514 TI - Molecular determinants of Listeria monocytogenes pathogenesis. PMID- 1312515 TI - Influence of immunization on Porphyromonas gingivalis colonization and invasion in the mouse chamber model. AB - The effects of immunization with invasive or noninvasive Porphyromonas (Bacteroides) gingivalis strains on the pathogenesis of infection in a mouse chamber model were examined. BALB/c mice were immunized by a single injection of heat-killed P. gingivalis invasive strain A7436 or W83 or noninvasive strain 33277, HG405, or 381 directly into subcutaneous chambers. P. gingivalis-specific antibody was detected in chamber fluid 21 days postimmunization, and mice were subsequently challenged by injection of exponential-phase P. gingivalis into chambers. Immunization with A7436 or W83 followed by challenge with A7436 protected mice against secondary abscess formation and death; however, P. gingivalis persisted in chambers for up to 14 days postchallenge. Immunization with noninvasive strain 33277, HG405, or 381 followed by challenge with invasive strain A7436 or W83 protected mice against secondary lesion formation and death. P. gingivalis was cultured from 33277- or HG405-immunized and nonimmunized animals to day 14. All P. gingivalis strains induced an immunoglobulin G response, as measured by an enzyme-linked immunosorbent assay and Western immunoblotting of P. gingivalis whole-cell and outer membrane protein preparations. Western blot analyses indicated that sera from mice immunized with different invasive and noninvasive strains recognized common P. gingivalis antigens. In summary, immunization with invasive P. gingivalis A7436 and W83 or noninvasive P. gingivalis 33277, HG405, and 381 protected mice from secondary lesion formation and death after challenge with invasive P. gingivalis A7436 or W83. P. gingivalis-specific antibody did not, however, inhibit the colonization of P. gingivalis within chambers. PMID- 1312516 TI - Porphyromonas gingivalis virulence in mice: induction of immunity to bacterial components. AB - Selected cell envelope components of Porphyromonas gingivalis were tested in a BALB/c mouse model in an attempt to elucidate further the outer membrane components of this putative oral pathogen that might be considered as virulence factors in host tissue destruction. Lipopolysaccharide (LPS), outer membrane, and outer membrane vesicles of P. gingivalis W50, ATCC 53977, and ATCC 33277 were selected to examine an immunological approach for interference with progressing tissue destruction. Mice were actively immunized with heat-killed (H-K) or Formalin-killed (F-K) whole cells or with the outer membrane fraction, LPS, or outer membrane vesicles of the invasive strain P. gingivalis W50. The induction of invasive spreading lesions with tissue destruction and lethality were compared among different immunization groups in normal, dexamethasone-treated (dexamethasone alters neutrophil function at the inflammatory site), and galactosamine-sensitized (galactosamine sensitization increases endotoxin sensitivity) mice after challenge infection with the homologous strain (W50) and heterologous strains (ATCC 53977 and ATCC 33277). Enzyme-linked immunosorbent assay analyses revealed significantly elevated immunoglobulin G and M antibody responses after immunization with H-K or F-K cells or the outer membrane fraction compared with those of nonimmunized mice. The killed whole-cell vaccines provided significantly greater protection against challenge infection in normal mice (decreased lesion size and death) than did either the outer membrane fraction or LPS immunization. The lesion development observed in dexamethasone-pretreated mice was significantly enhanced compared with that of normal mice after challenge with P. gingivalis. Immunization with P. gingivalis W50 provided less protection against heterologous challenge infection with P. gingivalis ATCC 53977; however, some species-specific antigens were recognized and induced protective immunity. Only viable P. gingivalis induced a spreading lesion in normal, dexamethasone treated, or galactosamine-sensitized mice; F-K or H-K bacteria did not induce lesions. The F-K and outer membrane vesicle immunization offered greater protection from lesion induction than did the H-K immunogen after challenge infection simultaneous with galactosamine sensitization. The H-K cell challenge with galactosamine sensitization produced 100% mortality without lesion induction, suggesting that LPS or LPS-associated outer membrane molecules were functioning like endotoxin. Likewise, P. gingivalis W50 LPS (1 micrograms per animal) administered intravenously produced 80% mortality in galactosamine sensitized mice. In contrast to the effects of immunization on lesion development, immunization with H-K or F-K cells or LPS provided no protection against intravenous challenge with LPS; 100% of the mice died from acute endotoxin toxicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1312517 TI - Biochemical characterization of Porphyromonas (Bacteroides) gingivalis collagenase. AB - A protease was purified from Porphyromonas gingivalis 1101, a clinical isolate, by sequential sodium dodecyl sulfate-polyacrylamide gel electrophoresis, substrate diffusion gel electrophoresis, and electroelution. The enzyme cleaved radiolabeled human basement membrane type IV collagen and the synthetic collagen peptide substrate for eukaryotic collagenases. It was inactivated by the thiol protease inhibitor N-ethylmaleimide but not by EDTA or EGTA [ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and activated by reducing agents such as beta-mercaptoethanol. The enzyme exists as an active precursor protein of molecular mass 94 kDa and undergoes proteolytic cleavage to 75-, 56-, and 19-kDa forms. Biotin-labeled collagen bound specifically to the 94-kDa form of the protein and to its cleavage products in ligand blots, suggesting a role for this enzyme not only in collagen degradation but also in adhesion to collagenous substrata. PMID- 1312519 TI - Age-dependent pulmonary clearance of Pseudomonas aeruginosa in a mouse model: diminished migration of polymorphonuclear leukocytes to N-formyl-methionyl-leucyl phenylalanine. AB - Ten-, 20-, and 35-day-old mice were subjected to an aerosol containing Pseudomonas aeruginosa. The lung clearance of the organism was decreased in mice under 20 days of age. This deficiency was accompanied by decreased migration of polymorphonuclear leukocytes (PMN) to the airways in response to the P. aeruginosa challenge. Similar results were obtained in both outbred, C5 sufficient Swiss mice and inbred, C5-deficient DBA/2 mice. The diminished clearance of P. aeruginosa was related to a transient, age-related decrease in PMN chemotaxis to formyl-methionyl oligopeptides. PMN chemotaxis levels similar to those seen in adults were regained by day 35 after birth. PMID- 1312520 TI - Apparent retrovirus-induced immunosuppression in a yearling llama. AB - Immunosuppression suspected to be associated with retrovirus infection was diagnosed in an 18-month-old female llama. The llama had a 6-month history of weight loss, intermittent lameness, and infections that were nonresponsive to treatment. Serial CBC indicated persistent nonregenerative anemia and leukopenia characterized by absolute neutropenia and lymphopenia. Functional hypoplasia of myeloid and erythroid cell lines was detected in serial bone marrow biopsy specimens. Notable pathologic findings included inadequate hematopoiesis, generalized lymphoid hypoplasia and plasma cell depletion, and pulmonary alveolar histiocytosis. Pneumocystis carinii cysts and viral particles of the size and morphologic features consistent with the retrovirus family were observed in lung sections examined by transmission electron microscopy. Antemortem macrophage and postmortem lymph node cultures were positive for reverse transcriptase activity. PMID- 1312518 TI - Adherence to respiratory epithelia by recombinant Escherichia coli expressing Klebsiella pneumoniae type 3 fimbrial gene products. AB - We examined the role of Klebsiella fimbrial types 1 and 3 in mediating adherence to human buccal and tracheal cells and to lung tissue sections. We found that clinical isolates of Klebsiella pneumoniae producing type 3 fimbriae and Escherichia coli HB101 containing a recombinant plasmid encoding expression of Klebsiella type 3 fimbriae (pFK10) demonstrated increased adherence to tracheal cells, trypsinized buccal cells, and lung tissue sections, in contrast to nonfimbriate and to type 1 fimbriate bacteria. Adherence by type 3 fimbriate bacteria was inhibited by purified type 3 fimbriae and Fab fragments derived from type 3 fimbrial-specific polyclonal immunoglobulin G. Type 3 fimbriae mediated attachment to the basolateral surface of tracheal cells and to the basal epithelial cells and the basement membrane regions of bronchial epithelia. Using an E. coli transformant (pDC17/pFK52), which expresses nonadherent P fimbrial filaments, along with the type 3 fimbrial adhesin (MrkD), we demonstrated that type 3 fimbrial attachment to respiratory cells was attributable to the MrkD adhesin subunit. Subsequent experiments demonstrated that the epithelial target of the type 3 fimbrial adhesin was most likely a peptide molecule rather than a carbohydrate. The results of this study demonstrate that, in vitro, the Klebsiella type 3 fimbrial adhesin mediates adherence to human respiratory tissue. PMID- 1312521 TI - WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. AB - WS-7338 A, B, C and D, novel endothelin receptor antagonists, have been isolated from fermentation broth of Streptomyces sp. No. 7338. These antagonists were purified from the culture mycelium by extraction with acetone, followed by carbon column chromatography and HPLC. Among them, WS-7338 B showed good activity in an endothelin receptor binding assay with an IC50 of 2.7 x 10(-7) M. PMID- 1312522 TI - WS-7338, new endothelin receptor antagonists isolated from Streptomyces sp. No. 7338. II. Biological characterization and pharmacological characterization of WS 7338 B. AB - WS-7338, produced by Streptomyces sp. No. 7338, was found to be a competitive and specific antagonist against ET-1 receptors in in vitro studies and WS-7338 B is also active in vivo. Furthermore, WS-7338 B was a specific antagonist for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues. PMID- 1312523 TI - Supplementation of ammoniated wheat straw: performance and forage utilization characteristics in beef cattle receiving energy and protein supplements. AB - Two experiments were conducted to evaluate performance and forage utilization characteristics of beef cattle fed ammoniated wheat straw (AWS) unsupplemented except for minerals or supplemented with energy and protein. In Exp. 1, 194 crossbred beef cows (BW = 472 kg) in late gestation were allotted by weight, breed type, and age during two consecutive winters to 12 drylot pens (three pens/treatment) for a 60-d feeding trial. The AWS (3% NH3 wt/wt) was tubground through a 7.6-cm screen, and cows were allowed ad libitum access to the AWS. In Exp. 2, 16 ruminally fistulated Angus x Hereford steers (BW = 300 kg) were blocked by weight and randomized to treatments in a 35-d intake-digestion trial. Daily supplementation treatments in both experiments were Control, no supplemental energy or protein; LSG, 1.36 kg of sorghum grain (SG); HSG, 2.72 kg of SG; and SG + SBM, 1.02 kg of SG + .34 kg of soybean meal (SBM). All animals received .23 kg of mineral mixture formulated to meet a pregnant cow's mineral requirements. Supplements LSG and SG + SBM were fed to provide the same daily ME, and HSG and SG + SBM were fed to provide the same daily CP. Cows were managed as one group during and after calving. In Exp. 1, all supplements increased gain (P less than .01) vs Control, and cows fed SG + SBM had higher (P = .05) gains than those fed LSG. The SG + SBM supplement increased (P less than .01) change in cow body condition score compared with LSG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312524 TI - Effect of light intensity on circadian profiles of melatonin, prolactin, ACTH, and cortisol in pigs. AB - Eleven crossbred barrows were housed in environmentally controlled rooms with an 8-h photoperiod. Pigs in one room received control illumination of 113 1x (CON; n = 6), and pigs in the other room received intense illumination of 1,783 1x (INT; n = 5) fluorescent light. Pigs were given at least 20 d of exposure to the environment before blood samples were taken every 3 h for 48 h. Data were analyzed by split-plot analysis of variance. Except for prolactin, no treatment x time interactions were noted for the hormone profiles evaluated (P greater than .10). Pigs in INT had greater (P less than .05) concentrations of prolactin in serum than pigs in CON at every sampling time. Concentrations of ACTH and cortisol in plasma were similar for INT (33.9 +/- 3.2 pg/mL of ACTH and 24.4 +/- 3.4 ng/mL of cortisol, respectively) and CON (34.9 +/- 3.0 pg/mL of ACTH and 31.3 +/- 3.1 ng/mL of cortisol, respectively). Within the INT treatment, serum melatonin concentrations were more than doubled (P less than .05) during darkness (66.8 +/- 9.3 pg/mL) compared with during light (30.4 +/- 9.3 pg/mL); however, within the CON treatment, concentrations during light and darkness did not differ (38.4 +/- 9.3 pg/mL and 42.9 +/- 9.3 pg/mL, respectively). Results indicate that light of greater intensity is required to entrain circadian rhythms of melatonin in serum of pigs. Furthermore, pigs may respond to bright light with greater secretion of prolactin, even under constant duration of photoperiod. PMID- 1312525 TI - Effects of nitrogen fertilization and maturity of bromegrass on nitrogen and amino acid utilization by cows. AB - Four nonlactating Holstein cows (593 kg) with ruminal cannulas were fed bromegrass hay that was fertilized with 0 or 89 kg of N/ha and harvested in the late-boot or full-head stage of maturity. Total tract apparent digestibility of N was less for full-head than for late-boot bromegrass (48 vs 64%; P less than .01) and was greater for N-fertilized than for unfertilized bromegrass (60 vs 52%, P less than .01). True N digestibility was greater (P less than .01) by cows fed late-boot hay than by those fed full-head bromegrass (85 vs 81%). Maturity did not affect N retention. Nitrogen fertilization increased N retained, both grams per day (70 vs 20; P less than .01) and as a percentage of N intake (P less than .01). Nitrogen and amino acid disappearance kinetics were determined in situ. Rate constants for N disappearance within rapidly and slowly degraded pools were not different among treatments, but because late-boot had a larger proportion of N in the rapidly degraded pool, overall disappearance rate for N was faster (P less than .05) for late-boot than for full-head bromegrass (12.0 vs 7.1 %/h). Treatment effects observed for individual amino acids were similar to those found for N. Both composition and kinetic data were needed to explain differences in N digestion and balance. Distribution of N within the forage had profound effects on the N economy of the cows. PMID- 1312526 TI - Forage systems for beef production from conception to slaughter: II. Stocker systems. AB - Fall weaned Angus calves grazed stockpiled 1) tall fescue (Festuca arundinacea Schreb.), 2) tall fescue-red clover (Trifolium pratense L.), or 3) tall fescue alfalfa (Medicago sativa L.) or were barn-fed, 4) tall fescue hay, 5) orchardgrass (Dactylis glomerata L.)-alfalfa hay, or 6) tall fescue silage from late October to early April during each of 5 yr. Infection of the fescue with Acremonium coenophialum ranged from 0 to 55%. There were two replications each of steers and heifers for each forage system in a completely random design. Each replicate was grazed by three Angus stockers, except for System 1, which was grazed by six stockers, for a total of 420 stockers. Each pasture replicate contained .8 ha (except System 1, which was 1.6 ha), and the stocking rate was one stocker per .27 ha. Fescue hay and silage were harvested each spring for barn fed systems from the area stockpiled for grazing by cattle in System 1. Nitrogen fertilizer (90 kg/ha) was applied in early spring and again in early August, before stockpiling; no N was applied to stockpiled fescue grown with legumes. Daily gains by calves grazing stockpiled fescue-alfalfa were greater (P less than .01) than by calves grazing stockpiled fescue-red clover or N-fertilized stockpiled fescue (.50, .33, and .34 kg/d, respectively), but fescue-alfalfa calves required more days (P less than .01) of supplemental hay feeding (105, 60, and 36, respectively). Calves fed fescue hay in the barn gained more (P less than .01) than those fed fescue silage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312527 TI - Phenotypic expression of the Pseudomonas syringae pv. syringae 61 hrp/hrm gene cluster in Escherichia coli MC4100 requires a functional porin. AB - Plants, in general, appear to be able to detect the presence of incompatible Pseudomonas syringae strains by a hypothetical cell-cell recognition process to initiate inducible defense mechanisms that contribute to disease resistance. A 25 kb hrp/hrm gene cluster isolated from P. syringae pv. syringae 61(pHIR11) enables Escherichia coli to elicit a hypersensitive response (HR), a plant response generally considered to be a manifestation of recognition and resistance. To identify the nature of the HR-eliciting signal produced by E. coli cells carrying pHIR11, bacterial surface features were surveyed by immunological and biochemical procedures. No immunoreactive epitopes or outer membrane proteins were detected that were associated with expression of the P. syringae pv. syringae 61 hrp/hrm cluster in E. coli MC4100. Phenotypic expression of the P. syringae pv. syringae 61 hrp/hrm cluster in E. coli MC4100, however, was found to be dependent upon ompC and ompF, which control outer membrane permeability to hydrophilic solutes. The results suggest that deployment of the HR-eliciting signal occurs via outer membrane porins and imply that a low-molecular-weight, hydrophilic factor mediates signal exchange between the bacterium and the responding plant cell. PMID- 1312528 TI - Hyperhemolytic phenomena associated with insertions of Tn916 into the hemolysin determinant of Enterococcus faecalis plasmid pAD1. AB - Members of the Tn916 family of conjugative transposons are able to insert themselves into Enterococcus faecalis hemolysin/bacteriocin plasmid pAD1 (and related elements) in such a way as to generate hyperexpression of the hemolysin/bacteriocin. To examine this phenomenon in more detail, E. faecalis (pAD1::Tn916) derivatives defective or altered in hemolysin expression were isolated and characterized with respect to production of the L (lytic) or A (activator) component (also known as CylA) and the specific location of the transposon. The mutants fell into five classes. Class 1 strains were nonhemolytic, and the related insertions mapped in a location known to affect expression of the L component. The other four classes varied from an inability to express hemolysin (class 2) to different degrees of hyperhemolytic expression (classes 3 to 5); the insertions in these classes mapped in a similar place within cylA, near the 3' end of the determinant. A previous study provided evidence that CylA is also necessary for bacteriocin immunity; however, these insertions did not destroy this function. (A Tn917 insertion in the 5' half of the determinant eliminates immunity.) In mutant classes 3 to 5, the presence of tetracycline enhanced hemolysin expression. In late-exponential-phase broth cultures, hemolysin could not be detected in supernatants of classes 2 to 5, in contrast to a wild-type control strain; however, different amounts of the L component could be detected, with the lowest in class 2 and greater-than-normal amounts in classes 3 to 5. Although nucleotide sequencing showed that the Tn916 insertions in classes 2 to 5 were at identical sites, the transposon junction sequences differed in some cases. The data indicated that cylA translation into the transposon would result in different truncation sites, and these differences were probably related to phenotype differences. PMID- 1312529 TI - Regulation of the pAD1-encoded sex pheromone response in Enterococcus faecalis: nucleotide sequence analysis of traA. AB - The Enterococcus faecalis plasmid pAD1 conjugatively transfers in response to a sex pheromone, cAD1, excreted by potential recipient cells. A key determinant responsible for regulation of pAD1 transfer is traA, which encodes a negative regulator also believed to function in signal sensing. In this study, we analyzed the nucleotide sequence and transcription of traA. A protein of 319 amino acids with a molecular weight of 37,856 was inferred and found to exhibit limited homology with several DNA-binding proteins. Analysis of Tn917-lac insertions resulting in transcriptional lacZ fusions within the 3' end of the traA transcript showed that it overlaps slightly with a convergently-transcribed C region transcript. Insertional mutations affecting TraA repressor function and signal sensing functions were localized. PMID- 1312530 TI - Characterization of stress-responsive behavior in Pseudomonas aeruginosa PAO: isolation of Tn3-lacZYA fusions with novel damage-inducible (din) promoters. AB - Although the pervasive soil and water microorganism Pseudomonas aeruginosa demonstrates heightened sensitivity to UV radiation, this species possesses a recA gene that, based on structural and functional properties, could mediate a DNA damage-responsive regulon similar to the SOS regulon of Escherichia coli. To determine whether P. aeruginosa encodes such stress-inducible genes, the response of P. aeruginosa to DNA-damaging agents including far-UV radiation (UVC) and the quinolone antimicrobial agent norfloxacin was investigated by monitoring the expression of fusions linking P. aeruginosa promoters to a beta-galactosidase reporter gene. These fusions were obtained by Tn3-HoHoI insertional mutagenesis of a P. aeruginosa genomic library. Eight different damage-inducible (din) gene fusions were isolated which lack homology to the P. aeruginosa recA gene. Expression of the three gene fusions studied, dinA::lacZYA, dinB::lacZYA, and dinC::lacZYA, increased following UVC and quinolone exposure but not following heat shock. Similar to E. coli SOS genes, the din genes were induced to different extents and with dissimilar kinetics following UVC irradiation. PMID- 1312531 TI - Cloning and sequence of Bacillus subtilis purA and guaA, involved in the conversion of IMP to AMP and GMP. AB - Bacillus subtilis genes purA, encoding adenylosuccinate synthetase, and guaA, coding for GMP synthetase, appear to be lethal when cloned in multicopy plasmids in Escherichia coli. The nucleotide sequences of purA and guaA were determined from a series of gene fragments isolated by polymerase chain reaction amplification, library screening, and plasmid rescue techniques. Identifications were based on amino acid sequence alignments with enzymes from other organisms. Comparison of the 5'-flanking regions of purA and guaA with the pur operon suggests similarities in mechanisms for gene regulation. Nucleotide sequences are now available for all genes involved in the 14-step pathway for de novo purine nucleotide synthesis in B. subtilis. PMID- 1312532 TI - Cloning and characterization of pathogenicity genes from Xanthomonas campestris pv. glycines. AB - Nonpathogenic mutants of Xanthomonas campestris pv. glycines 8ra were generated with N-methyl-N-nitro-N'-nitrosoguanidine to identify and characterize pathogenicity genes of the bacterium. A total of 16 nonpathogenic mutants were isolated from 2,000 colonies. One mutant, NP1, was chosen for further study. NP1 did not multiply in soybean cotyledons. A genomic library of strain 8ra was constructed in the cosmid pLAFR3, and the cosmids were tested for complementation in NP1. One cosmid clone, pIH1, which contained a 31-kb insert, complemented mutant NP1. A restriction map of pIH1 was constructed, and deletion analyses identified a 10-kb HindIII fragment that restored pathogenicity to NP1. Southern hybridization analysis indicated that DNA sequences in the 10-kb HindIII fragment are conserved among other X. campestris pathovars tested. Three regions responsible for restoring pathogenicity have been identified by Tn3-HoHo1 mutagenesis. A 2.7-kb ClaI fragment was sequenced, and two possible open reading frames (ORF1 and ORF2) were found. Results indicated that ORF2 but not ORF1 may be expressed in Escherichia coli and in X. campestris pv. glycines. The carboxy terminus of the potential polypeptide encoded by ORF2 has an amino acid sequence similar to that of the gamma subunit of oxaloacetate decarboxylase, which is involved in sodium ion transport in Klebsiella pneumoniae. PMID- 1312533 TI - The dehalogenase gene dehI from Pseudomonas putida PP3 is carried on an unusual mobile genetic element designated DEH. AB - As a result of the production of two dehalogenases (DehI and DehII), Pseudomonas putida PP3 utilized halogenated alkanoic acids, such as 2-monochloropropionic acid (2MCPA), as sole sources of carbon and energy. The DehI gene (dehI) was carried on a mobile genetic element (DEH) located on the chromosome of strain PP3. DEH recombined with target plasmid DNAs at high frequencies (e.g. 3.8 x 10( 4) per RP4.5 plasmid transferred). The regulated expression of dehI was detected in P. putida, Pseudomonas aeruginosa, and Escherichia coli strains containing derivative plasmids of RP4.5 and pWW0 recombined with DEH. Movement of DEH from the unstable RP4 derivatives pNJ5000 and pMR5 resulted in the insertion of DEH into the chromosome of RecA+ strains of P. putida but not in RecA+ nor RecA- strains of E. coli. Rescue of DEH from the chromosome of P. putida KT2441 onto plasmid RP4 involved recombination at a frequency (2.7 x 10(-4) per RP4 plasmid transferred) comparable to that observed in strain PP3. The DEH element was not classified as a conventional transposon because it did not move as a discrete DNA fragment: dehI-containing inserts in plasmid DNA targets varied in size between 6 and 13 kb. In addition, DEH exhibited a marked preference for insertion into a specific site on the plasmid pWW0, but its transposition, independent of host recombinational systems, remains to be demonstrated. However, the transposonlike characteristics of DEH included the conservation of restriction endonuclease sites, high-frequency recombination with different target replicons (plasmid and chromosomal DNA), and promiscuous insertion into plasmid RP4-based replicons. Therefore, it is proposed that DEH is an unusual mobile genetic element. PMID- 1312534 TI - Localization and functional analysis of structural and regulatory dehalogenase genes carried on DEH from Pseudomonas putida PP3. AB - Pseudomonas putida PP3 expressed two dehalogenases, DehI and DehII. The DehI gene (dehI) was located on a mobile DNA element (DEH) which inserted at high frequencies into target plasmids from its chromosomal location. From a recombinant TOL plasmid (pWW0) containing a 6.0-kb DEH element inserted into the plasmid's 5.6-kb EcoRI-G restriction endonuclease fragment, an 11.6-kb EcoRI fragment was cloned. Subcloning analysis and insertion mutagenesis produced a structural map of the DEH element and located the dehalogenase functions. The gene dehI was transcribed from a regulated promoter on DEH which was expressed in P. putida and Escherichia coli. The direction of transcription of dehI was determined, and it was also found to be under positive control, activated by an adjacent regulatory gene (dehRI). Expression of dehI in clones containing the intact DEH supported good growth on 2-monochloropropionate (2MCPA). Subclones lacking dehRI expressed dehI at levels which allowed only slow growth on 2MCPA, even when dehI expression was initiated from vector promoters. Expression of dehI in P. putida containing the intact DEH element required rpoN, suggesting that it was omega 54 dependent. The intact DEH element transferred to P. putida on a suicide plasmid donor pAWT34 (pBR325 replicon), and dehI was stably inherited, without vector DNA sequences, in transformants selected on 2MCPA. This indicated that the cloned DEH element contained functions associated with recombination. PMID- 1312535 TI - Structural relatedness of enteric bacterial porins assessed with monoclonal antibodies to Salmonella typhimurium OmpD and OmpC. AB - The immunochemistry and structure of enteric bacterial porins are critical to the understanding of the immune response to bacterial infection. We raised 41 monoclonal antibodies (MAbs) to Salmonella typhimurium OmpD and OmpC porin trimers and monomers. Enzyme-linked immunosorbent assays, immunoprecipitations, and/or Western immunoblot techniques indicated that 39 MAbs (11 anti-trimer and 28 anti-monomer) in the panel are porin specific and one binds to the lipopolysaccharide; the specificity of the remaining MAb probably lies in the porin-lipopolysaccharide complex. Among the porin-specific MAbs, 10 bound cell surface-exposed epitopes, one reacted with a periplasmic epitope, and the remaining 28 recognized determinants that are buried within the outer membrane bilayer. Many of the MAbs reacting with surface-exposed epitopes were highly specific, recognizing only the homologous porin trimers; this suggests that the cell-surface-exposed regions of porins tends to be quite different among S. typhimurium OmpF, OmpC, and OmpD porins. Immunological cross-reaction showed that S. typhimurium OmpD was very closely related to Escherichia coli NmpC and to the Lc porin of bacteriophage PA-2. Immunologically, E. coli OmpG and protein K also appear to belong to the family of closely related porins including E. coli OmpF, OmpC, PhoE, and NmpC and S. typhimurium OmpF, OmpC, and OmpD. It appears, however, that S. typhimurium "PhoE" is not closely related to this group. Finally, about one-third of the MAbs that presumably recognize buried epitopes reacted with porin domains that are widely conserved in 13 species of the family Enterobacteriaceae, but apparently not in the seven nonenterobacterial species tested. These data are evaluated in relation to host immune response to infection by gram-negative bacteria. PMID- 1312538 TI - Anabolic steroid use among substance abusers in treatment. AB - BACKGROUND: Increasing illicit use of anabolic steroids in adolescent and young adult populations has been reported. To determine the scope of this problem and its relationship to psychoactive substance abuse, we evaluated the prevalence of anabolic steroid use among individuals seeking inpatient treatment for substance abuse. METHOD: A randomized mail survey of 175 inpatient substance abuse treatment directors elicited information regarding the prevalence of anabolic steroid use for inpatients treated in 1989 and the first half of 1990. Additionally, directors were surveyed for experience with DSM-III-R psychoactive substance dependence criteria for anabolic steroid use. RESULTS: Only 19% of centers responding had treated at least one individual using anabolic steroids. Facilities encountering anabolic steroid users reported a prevalence of less than 1% among all admissions. Anabolic steroid users were seen more commonly in privately funded facilities. Directors reported a majority of anabolic steroid users had at least three DSM-III-R psychoactive substance dependence criteria for anabolic steroid use. Treatment directors rarely found anabolic steroid use acknowledged as a problem by users and rarely found anabolic steroid use a primary reason for treatment. CONCLUSION: Users of illicit anabolic steroids may have significant clinical differences compared with users of other psychoactive substances of abuse and dependence. PMID- 1312537 TI - Anaerobic induction of the alkylation-inducible Escherichia coli aidB gene involves genes of the cysteine biosynthetic pathway. AB - The Escherichia coli aidB gene is a component of the adaptive response to alkylation damage. This gene is subject to two different forms of induction: an ada-dependent alkylation induction and an ada-independent induction that occurs when cells are grown anaerobically (M. R. Volkert, L. I. Hajec, and D. C. Nguyen, J. Bacteriol. 171:1196-1198, 1989; M. R. Volkert, and D. C. Nguyen, Proc. Natl. Acad. Sci. USA 81:4110-4114, 1984). In this study, we isolated and characterized strains bearing mutations that specifically affect the anaerobic induction pathway. This pathway requires a functional cysA operon, which encodes sulfate permease. Mutations in cysA block this pathway of aidB induction. In contrast, mutations in either cysH, cysD, cysN, or cysC result in elevated levels of aidB expression during aerobic growth. These results indicate that the sulfate transport genes perform a role in anaerobic induction of the aidB gene and suggest that growth under anaerobic conditions may modify either the function or the expression of gene products encoded by the cysA operon. PMID- 1312536 TI - Surface presentation of Shigella flexneri invasion plasmid antigens requires the products of the spa locus. AB - An avirulent, invasion plasmid insertion mutant of Shigella flexneri 5 (pHS1059) was restored to the virulence phenotype by transformation with a partial HindIII library of the wild-type invasion plasmid constructed in pBR322. Western immunoblot analysis of pHS1059 whole-cell lysates revealed that the synthesis of the invasion plasmid antigens VirG, IpaA, IpaB, IpaC, and IpaD was similar to that seen in the corresponding isogenic S. flexneri 5 virulent strain, M90T. IpaB and IpaC, however, were not present on the surface of pHS1059 as was found in M90T, suggesting that the transport or presentation of the IpaB and IpaC proteins onto the bacterial surface was defective in the mutant. pHS1059 was complemented by pWR266, which carried contiguous 1.2- and 4.1-kb HindIII fragments of the invasion plasmid. pHS1059(pWR266) cells were positive in the HeLa cell invasion assay as well as colony immunoblot and enzyme-linked immunosorbent assays, using monoclonal antibodies to IpaB and IpaC. These studies established that the antigens were expressed on the surface of the transformed bacteria. In addition, water extraction of pHS1059 and pHS1059(pWR266) whole cells, which can be used to remove IpaB and IpaC antigens from the surface of wild-type M90T bacteria, yielded significant amounts of these antigens from pHS1059(pWR266) but not from pHS1059. Minicell and DNA sequence analysis indicated that several proteins were encoded by pWR266, comprising the spa loci, which were mapped to a region approximately 18 kb upstream of the ipaBCDAR gene cluster. Subcloning and deletion analysis revealed that more than one protein was involved in complementing the Spa- phenotype in pHS1059. One of these proteins, Spa47, showed striking homology to ORF4 of the Bacillus subtilis flaA locus and the fliI gene sequence of Salmonella typhimurium, both of which bear strong resemblance to the alpha and beta subunits of bacterial, mitochondrial, and chloroplast proton translocating F0F1 ATPases. PMID- 1312539 TI - The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. AB - We examined the effect of blockade of N-methyl-D-aspartate (NMDA) and non-NMDA subtype glutamate receptors on anoxic depolarization (AD) and cortical spreading depression (CSD). [K+]e and the direct current (DC) potential were measured with microelectrodes in the cerebral cortex of barbiturate-anesthetized rats. NMDA blockade was achieved by injection of (+)-5-methyl-10,11-dihydro-5H dibenzo[a,d]cyclohepten-5,10-imine maleate [MK-801; 3 and 10 mg/kg] or amino-7 phosphonoheptanoate (APH; 4.5 and 10 mg/kg). Non-NMDA receptor blockade was achieved by injection of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX; 10 and 20 mg/kg). MK-801 and APH blocked CSD, while NBQX did not. In control rats, the latency from circulatory arrest to AD was 2.1 +/- 0.1 min, while the amplitude of the DC shift was 21 +/- 1 mV, and [K+]e increased to 50 +/ 6 mM. All variables remained unchanged in animals treated with MK-801, APH, or NBQX. Finally, MK-801 (14 mg/kg) and NBQX (40 mg/kg) were given in combination to examine the effect of total glutamate receptor blockade on AD. This combination slightly accelerated the onset of AD, probably owing to circulatory failure. In conclusion, AD was unaffected by glutamate receptor blockade. In contrast, NMDA receptors play a crucial role for CSD. PMID- 1312540 TI - Regional distribution and kinetics of three sites on the GABAA receptor: lack of effect of portacaval shunting. AB - The regional distribution of binding sites on the GABAA receptor and their kinetic parameters were measured by quantitative autoradiography in brains from normal rats and rats with a portacaval shunt, a model of portal systemic encephalopathy in which GABA neurotransmission may be altered. The ligands used were [3H]flunitrazepam (a benzodiazepine-site agonist), [3H]-Ro15-1788 (a benzodiazepine-site antagonist), [3H]muscimol (a GABA-site agonist), and [35S]t butylbicyclophosphorothionate (35S-TBPS, a convulsant that binds to a site near the chloride channel). Some brains were analyzed by computerized image analysis and three-dimensional reconstruction. The regional distribution of binding of the benzodiazepines was very similar, but the patterns obtained with [3H]muscimol and [35S]TBPS were different in many areas, suggesting a heterogeneous distribution of several subtypes of the GABAA receptor. The kinetic parameters were determined in brain regions for [3H]flunitrazepam, [3H]Ro15-1788, and [3H]muscimol. For each ligand, the Kd showed a significant heterogeneity among brain regions (at least threefold), contrary to conclusions drawn from earlier studies. In portacaval shunted rats, binding of all four ligands was essentially unchanged from that in control rats, indicating that, if there was an abnormality in GABA neurotransmission during portal systemic shunting, it was not reflected by altered binding to the main sites on the GABAA receptor. PMID- 1312541 TI - Mineralocorticoids and mineralocorticoid receptors in mononuclear leukocytes in patients with pregnancy-induced hypertension. AB - To examine the role of mineralocorticoids in the pathophysiology of pregnancy induced hypertension (PIH), we studied plasma aldosterone and 18 hydroxycorticosterone levels in 25 women with PIH and 25 normal pregnant women, as controls. Furthermore, we evaluated the mineralocorticoid receptor (MR) status in mononuclear leukocytes in the 2 groups. MR count was significantly (P less than 0.0005) decreased in the PIH group (148 +/- 9 binding sites/cell) compared with the control group (300 +/- 17 binding sites/cell; mean +/- SEM). Plasma aldosterone in women with PIH was 281 +/- 61 pmol/L; in normal pregnant women it was 697 +/- 172 pmol/L (P less than 0.025). Plasma 18-hydroxycorticosterone was also significantly (P less than 0.025) lower (PIH, 1071 +/- 149 pmol/L; controls, 1907 +/- 318 pmol/L). These values were determined at the onset of clinical symptoms of PIH. These results cannot be explained by receptor down-regulation due to higher levels of mineralocorticoids in PIH; a hitherto unknown mineralocorticoid may, thus, be responsible for the hypertension and altered MR status. PMID- 1312542 TI - Ras mutations in human pituitary tumors. AB - The cellular basis for pituitary neoplasia is poorly understood. Mutations that activate the ras protooncogenes have been identified in a number of different types of human cancers and potentially represent one of the genetic alterations that occur in pituitary tumors. In this study we examined 19 pituitary tumors for the occurrence of ras mutations. The tumor types included 11 nonfunctioning adenomas, 6 somatotroph adenomas, and 2 prolactinomas. Each of the three ras genes (K-ras, N-ras, and H-ras) was amplified from pituitary tumor DNA using the polymerase chain reaction. Oligonucleotide-specific hybridization was used to screen for mutations that inhibit GTPase activity and cause activation of the ras oncogene. No ras mutations were observed in 18 of the pituitary adenomas. However, a mutation was identified in codon 12 of the H-ras gene (Gly to Val) in a recurrent prolactinoma that was highly invasive and ultimately proved to be fatal. We conclude that ras mutations are uncommon in pituitary adenomas, but may provide a marker for highly invasive tumors. PMID- 1312544 TI - Bibliography of the current world literature in hypertension. PMID- 1312543 TI - Mineralocorticoid effector mechanism in preeclampsia. AB - Mineralocorticoid effector mechanisms were evaluated in 29 patients with preeclampsia and in 25 uncomplicated pregnancies by measurement of plasma aldosterone, levels of mineralocorticoid receptor (MR) in mononuclear leucocytes, and subtraction potential difference (SPD; rectal minus oral values). Mean values for plasma aldosterone were not different between the two groups, but significant differences were observed for MR (preeclampsia, 81 +/- 44 receptors/cell; controls, 306 +/- 168) and SPD (preeclampsia, 65 +/- 7 mV; controls, 12 +/- 5 mV). In six cases we determined MR, plasma aldosterone, and SPD in patients with preeclampsia before and 3 months after delivery. MR were reduced before delivery (96 +/- 27 receptors/cell), and SPD increased (64 +/- 8 mV), with both parameters normalizing after delivery (MR, 242 +/- 79; SPD, 14.0 +/- 4 mV). Aldosterone levels returned to normal nonpregnant values after delivery. These data suggest an important role for abnormalities in mineralocorticoid effector mechanisms in the etiology of preeclampsia and could be an useful marker for diagnosis. PMID- 1312545 TI - Increased level of atrial natriuretic peptide messenger RNA in the hypothalamus and brainstem of spontaneously hypertensive rats. AB - OBJECTIVE: The aim of this study was to investigate atrial natriuretic peptide (ANP) gene expression in the central nervous system (CNS) during hypertension. METHODS: We measured and compared immunoreactive atrial natriuretic peptide (irANP) and ANP messenger RNA (mRNA) in the hypothalamus and brainstem of 17-week old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto (WKY) rats using ribonuclease (RNase) protection assay for ANP mRNA and a specific radioimmunoassay for irANP. RESULTS: RNase protection assay revealed that the concentrations of ANP mRNA in the hypothalamus and brainstem of SHR were higher than those of WKY rats. IrANP concentrations in the hypothalamus and brainstem of SHR were determined by a specific radioimmunoassay and found to be higher than those of WKY rats. Elevated mRNA levels in the hypothalamus and brainstem of SHR indicated that increased level of irANP in the CNS resulted from increased synthesis of ANP. CONCLUSION: We propose that increased synthesis of brain ANP in SHR may reflect a compensatory mechanism induced by hypertension. PMID- 1312546 TI - Central interaction between endothelin and brain natriuretic peptide on vasopressin secretion. AB - OBJECTIVE: To examine the interaction between i.c.v. administration of endothelin and brain natriuretic peptide (BNP) on vasopressin (AVP) secretion in unanesthetized, freely moving rats. METHODS: I.c.v. cannulation and femoral artery catheterization were performed 7-8 days and 2 days before the experiment, respectively. Endothelin and BNP were injected into the third ventricle through the guide cannula. One millilitre of blood was collected for AVP measurement 30 min before and 10 min after i.c.v. injection. RESULTS: Central administration of endothelin (20 or 40 pmol/2 microliters) dose-dependently evoked the elevation of plasma AVP levels. Preinjection of BNP (0.2 or 1 nmol/3 microliters, i.c.v.) dose dependently attenuated central endothelin (40 pmol/2 microliters)-induced plasma AVP secretion. CONCLUSIONS: We have already reported that BNP attenuated central endothelin-induced pressor response and plasma catecholamine secretion. Taken together, the results indicate that BNP attenuated central endothelin-induced pressor response, at least partially, by suppressing sympathetic nervous system activation and plasma AVP secretion. PMID- 1312548 TI - Lies, damned lies--or statistics? PMID- 1312547 TI - The effect of chronic bilateral nephrectomy on plasma and brain angiotensin. AB - OBJECTIVE: To prove the independence of local tissue renin-angiotensin system (RAS) in brain from classical kidney RAS, we measured local angiotensin levels in bilaterally nephrectomized rats which had been dialyzed with a dialysis technique to greatly prolong survival time. DESIGN: Two groups of animals were used: (1) bilaterally nephrectomized rats with intraperitoneal dialysis, where both kidneys were surgically removed; and (2) controls with intact kidneys and dialysis. By using this protocol, we were able to study plasma and brain angiotensins 5 days after nephrectomy (no longer periods have been attempted). METHODS: Plasma sodium, potassium and pH were monitored while rats were dialyzed four times a day. Plasma samples and brain areas were obtained and angiotensin II measured by radioimmunoassay and high-pressure liquid chromatography (HPLC). RESULTS: Plasma angiotensin II was significantly diminished in the nephrectomized rats but was still detectable, the levels being above the minimal detectable value. The identity of angiotensin I and angiotensin II detected by radioimmunoassay was confirmed by HPLC. In the brain, angiotensin II content was significantly increased in all areas studied. The highest increments were in hypothalamus and brain stem. CONCLUSIONS: Our results demonstrate that: (1) brain angiotensin II is regulated independently of peripheral angiotensin II; and (2) a reduced plasma angiotensin II persists 5 days after bilateral nephrectomy. We conclude that the angiotensin II in the plasma was derived from non-renal tissue and the results support the conclusion that tissue RAS has paracrine and autocrine functions independent of the endocrine function of circulating plasma angiotensin. PMID- 1312549 TI - Renal sites of action of physiological increases in plasma atrial natriuretic factor concentration in essential hypertension. AB - OBJECTIVES: To investigate the renal, haemodynamic and neurohormonal responses to low-dose infusions of atrial natriuretic factor (ANF) in hypertensive humans. DESIGN: Ten patients with mild-to-moderate essential hypertension received incremental infusions of 3 and 6 ng/kg per min ANF or vehicle alone whilst on a constant dietary sodium intake. A 90-min basal clearance period was followed by two 2-h infusion periods, with urine collection in the last 90 min of each period. In each of the three clearance periods, glomerular filtration rate (GFR), renal tubular function, and the activity of the renin-angiotensin and sympathetic nervous systems were determined. METHODS: The renal sites of ANF action were established by simultaneous measurements of 51Cr-ethylenediaminetetraacetate lithium and sodium clearances. Plasma concentrations of neurohormones were measured by radioimmunoassays. RESULTS: Plasma ANF concentrations increased by 1.6- and 2.5-fold during the lower and higher ANF infusion rates, respectively. Plasma cyclic guanosine monophosphate concentrations increased in parallel. ANF caused no changes in supine systolic and diastolic blood pressure or in heart rate. In contrast, haematocrit values increased progressively across the study. The renal effects of ANF administration were characterized by an unaltered GFR and significant increases in the renal clearances of lithium (a marker of end proximal fluid delivery) and sodium when compared with vehicle infusions, whereas urine flow did not change. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly. Plasma concentration of active renin decreased during ANF infusions, but no significant changes in plasma levels of renin substrate, angiotensin I, angiotensin II or aldosterone were observed. A subtle activation of the sympathetic nervous system was indicated by a moderate increase in plasma noradrenaline during the ANF infusions. CONCLUSIONS: These results indicate that even small increases in plasma ANF, as can be found during physiological conditions, induce natriuresis in patients with essential hypertension by enhancing fluid delivery from the proximal tubules, in addition to impairing distal fractional sodium reabsorption. With minor exceptions, the ANF infusions caused qualitatively and quantitatively similar renal, haemodynamic and endocrine effects in the hypertensive patients as in a previously studied group of normotensive subjects. PMID- 1312550 TI - Existence of renin in the endothelium of human artery. AB - OBJECTIVE: The existence and localization of renin in situ was examined in human arteries under non-pathological conditions. DESIGN: Biochemical and immunohistochemical procedures were adopted to examine the existence of renin in human gastroepiploic arteries using an antibody raised against human recombinant renin or a specific renin inhibitor. METHODS: (1) Renin activity (angiotensin I generating activity sensitive to antihuman recombinant renin antibody or a specific renin inhibitor) in the homogenate of human gastroepiploic arteries with and without endothelium was compared; (2) vascular renin was immunohistochemically stained using a modified avidin-biotin-peroxidase complex method. RESULTS: (1) Renin activity in human gastroepiploic arteries with endothelium was significantly higher than in those without endothelium; (2) immunoreactive staining selectively occurred in the endothelial cells of human gastroepiploic arteries. CONCLUSIONS: Renin is present in endothelial cells of human arteries under non-pathological conditions. Endothelial renin may play a role in the control of vascular tone through local production of angiotensin II. PMID- 1312551 TI - The effect of angiotensin II on platelet intracellular free calcium concentration in human pregnancy. AB - OBJECTIVES: The primary objective of this study was to determine the effect of i.v. angiotensin II infusion on platelet intracellular free calcium concentration in potentially hypertensive primigravid women. DESIGN: Patients at 28-32 weeks gestation were selected on the basis of a diastolic pressure less than or equal to 80 mmHg taken at the antenatal clinic visit. METHODS: An angiotensin II infusion test (4-16 ng/kg per min) was performed in 13 women. Platelet intracellular free calcium concentration, platelet angiotensin II binding site density and plasma angiotensin II concentration were measured before and at the end of the infusion. Pregnancy outcome (normotension or hypertension) was recorded. RESULTS: Platelet intracellular free calcium concentration rose in 12 of 13 women during angiotensin II infusion. This rise was not directly correlated with initial or final platelet angiotensin II binding site density, plasma angiotensin II concentration or the evoked change in systolic or diastolic blood pressure. Five women subsequently developed pregnancy-induced hypertension. Although basal platelet intracellular free calcium concentration did not differ between the two groups, platelet intracellular free calcium concentration rose twice as much in response to angiotensin II in the five hypertensive pregnant women. There was a 12-fold increase in platelet angiotensin II binding in the future hypertensives, although basal angiotensin II was the same in the two groups. CONCLUSION: The enhanced rise in platelet intracellular free calcium concentration in response to angiotensin II administration in women who subsequently became hypertensive, together with their increased angiotensin II binding site density suggest a possible enhanced stimulus-effect coupling. Pregnancy-induced hypertension is a state of marked vasoconstriction, with an enhanced pressor response to angiotensin II. These data supply grounds for a hypothesis concerning the mechanism. PMID- 1312552 TI - Extracellular fluid volumes in pregnancy-induced hypertension. AB - OBJECTIVES: Reduction in plasma volume (Pvol) of women with pregnancy-induced hypertension (PIH; preeclampsia) has both physiological and clinical implications. This study was undertaken to determine the following variables in women with PIH: (1) the incidence of reduced Pvol; (2) the distribution of total extracellular fluid volume (ECFV); (3) the relationship between Pvol and birth weight; and (4) whether any readily available clinical or laboratory parameters predict the presence of reduced Pvol. SETTING: Teaching hospital obstetric unit and antenatal clinic. PARTICIPANTS: Forty-nine primigravidae with PIH (28 mild, 21 severe), 54 normotensive primigravidae and 25 non-pregnant controls. DESIGN: Pvol was measured using Evans Blue dye and ECFV as the mannitol space. These measures were compared amongst groups, and also within groups for those with PIH, according to the severity of their disorder and the presence of proteinuria or oedema. Blood pressure, haematocrit, uric acid and serum albumin were also evaluated as predictive indices of reduced Pvol in women with PIH. RESULTS: Pvol, ECFV and the Pvol:ECFV ratio all increased during normal pregnancy. Pvol in women with PIH was reduced compared with normal pregnancy and correlated significantly with birth weight. Total ECFV was unchanged in women with PIH, but their Pvol:ECFV ratio was significantly reduced compared with normal pregnancy. Although there was a significant correlation between Pvol and haematocrit in women with PIH, haematocrit was a poor predictor for reduced Pvol. Diastolic blood pressure greater than 100 mmHg, persistent proteinuria and severe PIH were the only reliable positive predictors of a reduced Pvol. CONCLUSIONS: Pvol is related to birth weight, but is reduced in only approximately half of women with PIH. This reduced Pvol is the result of maldistribution, not loss, of total ECFV, and can be predicted by high diastolic blood pressure, proteinuria or other clinical signs of severity, but not by haematocrit. PMID- 1312553 TI - Effects of essential hypertension and antihypertensive medications on sweat formation. AB - OBJECTIVE: Sweat volume and ionic composition depend to a large extent upon the cytosolic free calcium level in secretory sweat cells and sodium and potassium transport in the reabsorptive sweat duct. Since essential hypertension and its treatment with antihypertensive drugs is likely to be associated with altered cellular ionic regulation, the objective of this research was to explore sweat formation and sweat parameters in hypertensive and normotensive subjects. DESIGN: Black and white hypertensive and normotensive subjects of both genders were studied. Essential hypertensives were on or off antihypertensive medication. METHODS: Pilocarpine iontophoresis was used to induce sweat in a 5-cm2 area of the middle forearm. Sweat was analyzed for volume, sodium and potassium concentrations. RESULTS: Females demonstrated lower sweat volumes after pilocarpine stimulation than males. Untreated hypertensive white males exhibited a higher pilocarpine-induced sweat volume and sweat sodium excretion than normotensive white males, whilst hypertensive white males on antihypertensive medication showed a lower sweat volume and sweat sodium excretion than both normotensive white males and untreated essential hypertensive white males. Although untreated hypertensive white females did not show significant alterations in sweat parameters, treated hypertensive white females exhibited lower sweat volume and sweat sodium excretion than both the normotensive and untreated essential hypertensive white females. These hypertension and drug related alterations were not present in hypertensive black males and females. CONCLUSIONS: The results are consistent with the heterogeneous nature of essential hypertension and the diversity of the response to antihypertensive therapy. They suggest that the effect of antihypertensive medication on sweat formation is mediated through cytosolic free calcium. PMID- 1312554 TI - Differential regulation of protein synthesis in smooth muscle cells from normotensive and spontaneously hypertensive rats by a three-dimensional matrix of type I collagen. AB - OBJECTIVE: The objective of this study was to gain insight into the metabolic and morphological properties of smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) when cultured in vivo under similar conditions. DESIGN: Three-dimensional cell-collagen systems represent living tissue equivalents in vitro and simulate natural conditions more closely than conventional monolayer cultures. METHODS: The effect of a three-dimensional matrix of type I collagen on ultrastructure, total protein and collagen synthesis and cell cycle distribution of SMC from SHR and normotensive Wistar-Kyoto (WKY) rats was studied. RESULTS: Collagen lattice-cultured SMC from SHR and WKY rats showed the synthetic phenotype, i.e. the cytoplasm was filled with organelles characteristic of secretory protein synthesis. There was a decrease in the percentage of cells in the 5 phase compared with monolayer cultures. Total protein synthesized by SMC from SHR and WKY rats in lattices was lowered compared with monolayer cultures. However, reduction of protein synthesis in SMC from SHR was less than in SMC from WKY rats. Differences in the proportion of collagen in SMC from SHR and WKY rats were not demonstrable in collagen lattice cultures. CONCLUSION: The present study suggests that a three-dimensional matrix of type I collagen may modulate total protein synthesis in SMC from SHR and WKY rats. However, cells from SHR react less to this matrix than those from WKY rats. PMID- 1312555 TI - Nailfold microcirculation in normotensive and essential hypertensive subjects, as assessed by video-microscopy. AB - OBJECTIVE: To compare morphological and hemodynamic parameters of skin microcirculation in the fingertip in patients with essential hypertension and normotensive control subjects. DESIGN: Consecutive sample of patients. METHODS: Digital capillary blood flow measurements under normal and cooled conditions were assessed by nailfold video capillaroscopy using the technique of flying spot. RESULTS: There was a significant reduction in capillary density in hypertensive patients, compared with normotensive subjects. There was a correlation between capillary density and mean diastolic blood pressure. After local cooling the frequency of the blood flow stop was significantly higher in hypertensive patients. CONCLUSION: The finding of abnormal vasoconstriction in finger microcirculation in essential hypertension suggests a vasospastic tendency in the disease. PMID- 1312556 TI - A low-sodium diet supplemented with fish oil lowers blood pressure in the elderly. AB - OBJECTIVE: To examine effects of dietary fish oil supplementation with sodium restriction on blood pressure in the elderly. DESIGN: In a double-blind dietary intervention lasting 4 weeks, parallel comparisons of blood pressure were made in volunteers assigned to one of four treatment groups: fish oil and low sodium; fish oil and normal sodium; sunflower oil and low sodium; or sunflower oil and normal sodium. SETTING: Subjects lived at home and attended our nutrition research clinic at fortnightly intervals for dietary counselling and blood pressure measurement. PARTICIPANTS: Health volunteers aged 60-80 years were sought by advertisement. A total of 114 men and women were enrolled in two cohorts; 106, with an initial mean blood pressure of 132/77 mmHg, satisfactorily completed the study. INTERVENTION: All subjects adopted a low-sodium diet and dietary changes were effected by double-blind administration of slow-release sodium chloride or placebo tablets, along with capsules containing either fish or sunflower oil. MAIN OUTCOME MEASURE: The primary measure was the within-subject change in blood pressure after 4 weeks of intervention in each dietary treatment group. RESULTS: Urinary sodium excretion in subjects on low-sodium diets decreased whilst potassium excretion was unaffected. Systolic blood pressure (SBP) fell in the group taking sunflower oil with low sodium, but there was only a transient fall in diastolic blood pressure (DBP). In those taking fish oil with normal sodium, the change in blood pressure was not significant, except after adjustment for initial blood pressure and weight changes. When fish oil was combined with low sodium, however, both SBP and DBP were substantially reduced; the reduction in DBP was significantly greater than in the other treatment groups. CONCLUSION: Dietary fish oil and sodium restriction can interact to lower DBP in the elderly. PMID- 1312557 TI - Basic methodology in the molecular characterization of genes. AB - PURPOSE: During the past two decades, molecular biology techniques have had an increasing impact upon hypertension research. This article will thus review the basic methodology in this field. CONTENTS: Protocols are described for the establishment of a genomic library and its use for the cloning of specific genes, as well as methods for the detection and sequencing of DNA. In addition, techniques to detect and quantify specific messenger RNA, such as Northern blotting, ribonuclease protection assay and in situ hybridization, and the reporter gene approach for the analysis of regulatory gene sequences, are included. The polymerase chain reaction which, as a newly established technique to detect and amplify DNA, has exerted a strong influence upon all areas of molecular biology is the subject of the concluding paragraph. CONCLUSIONS: Molecular biology techniques may be of substantial help in revealing the cause of hypertension and developing tools to prevent and treat this disorder. PMID- 1312558 TI - The interaction of norepinephrine excretion with blood pressure and race in children. AB - OBJECTIVE: The purpose of this study was to examine the relationship between urinary norepinephrine excretion and blood pressure, and to determine the influence of race on this relationship. Urinary norepinephrine was used to estimate renal and systemic sympathetic nervous system (SNS) activity. DESIGN: Fifty black and forty-nine white normotensive children aged 9-14 years had their blood pressure measured, and provided an overnight urine sample. METHODS: Urinary norepinephrine was measured by radioenzymatic assay. Excretion rates of norepinephrine were expressed per milligram urinary creatinine. RESULTS: Black children had age-adjusted mean diastolic and systolic blood pressure which was higher than in white children. For both blacks and whites, nocturnal urinary norepinephrine excretion rates were positively related to age-adjusted mean diastolic blood pressure, but not to systolic blood pressure. Norepinephrine excretion was significantly lower in black children compared with white children. CONCLUSION: These findings suggest that the higher blood pressures in black children were not causally related to greater SNS activity. The SNS may have been suppressed in black children, possibly by a greater expansion of plasma volume, alternatively, black children may have been more sensitive to the influences of the SNS than white children. PMID- 1312559 TI - 1991 guidelines for the prevention of hypertension and associated cardiovascular disease. Joint World Health Organization/International Society of Hypertension Meeting. PMID- 1312560 TI - Laboratory infection with human parvovirus B19. PMID- 1312561 TI - The possible role of Coxsackie A and echo viruses in the pathogenesis of type I diabetes mellitus studied by IgM analysis. AB - IgM antibodies to Coxsackie B virus (CBV) have recently been observed in the serum of a relatively high proportion of children with newly diagnosed insulin dependent diabetes mellitus (IDDM). In the present study, 108 IDDM patients below the age of 15 years, diagnosed during the period 1976 to 1985, were investigated at the onset of their disease by mu-antibody-capture radioimmunoassay (RIA) of IgM against seven different enterovirus antigens, namely virions of CBV serotypes 1-5 (CBV 1-5) and procapsids of CBV 3 and CBV 5. As has been shown the RIAs with virions give type-specific or narrow type-specific reactions, whereas procapsids react with IgM against both homotypic and heterotypic enteroviruses. The annual frequency of IgM against virions varied between 15 and 76% (mean 38%). IgM against CBV3 and CBV2 predominated, but IgM against the other serotypes was also observed. When procapsids were used as antigen, the frequency of IgM varied between 11 and 86% (mean 63%). With virions and procapsids, the corresponding variation was 44-100% (mean 70%). The total number of patients exhibiting virion IgM was 41, whereas procapsid-IgM alone [indicating an infection with Coxsackie A virus (CAV) and/or echo virus (EV)] was detected in 36 patients. For 2 of the years, samples of serum from control groups were included. These showed a significantly lower frequency of IgM in both the virion and the procapsid RIAs. It is concluded that not only infection with CBV but also that with other enteroviruses, such as CAV and/or EV, may be involved in the pathogenesis of IDDM in children. PMID- 1312562 TI - An assessment of sputum induction as an aid to diagnosis of respiratory infections in the immunocompromised child. AB - Sputum induction using nebulised hypertonic saline was performed in two groups of immunocompromised children, one group with symptoms of respiratory infection and one group without. The asymptomatic group were bone marrow transplant (BMT) recipients, all seropositive for cytomegalovirus infection (CMV). Organisms were identified in three of 14 induced sputum specimens obtained from the symptomatic group (CMV N = 1, Haemophilus influenzae N = 2), but in none of 12 specimens from the asymptomatic group. Adverse effects encountered were minor. Four symptomatic patients with negative induced sputum samples underwent bronchoalveolar lavage, and no further organisms were identified. Sputum induction can be a useful adjunct to the diagnosis of respiratory pathogens in this group of patients. PMID- 1312563 TI - Control of invasive pulmonary aspergillosis with oral itraconazole in a bone marrow transplant patient. AB - Pulmonary aspergillosis following bone marrow transplantation carries a mortality of 94%, irrespective of current treatment. We treated a patient who had acquired aspergillosis some 80 days after allogeneic bone marrow transplantation, with oral itraconazole, 600 mg daily. After initial deterioration, clinical and radiographic resolution occurred during 3 months of therapy despite severe graft vs.-host and cytomegalovirus disease. Itraconazole should be considered for therapy of pulmonary aspergillosis in this and other immunocompromised settings. PMID- 1312564 TI - Influenza C virus infection in France. AB - Little is known of the epidemiology of influenza C virus infections in western Europe and of the exact role of this agent in acute viral respiratory infections. Several tests may be used for detecting antibodies against this agent but the significance of their respective results is not clear. A total of 301 samples of serum was collected from persons aged from 4 months to 88 years living in France in 1988. The samples were tested for the presence of antibodies to influenza C virus by haemagglutination-inhibition (HI) tests and ELISA. The specificity of the results was checked by immunoblotting and by antibody absorption with staphylococcal protein A. Significant HI activity was found in 61% of the 301 samples tested, titres ranging from 20-320; 70% were positive by ELISA with titres ranging from 500 to 32,000. The population tested was divided into four age groups: 0-15 years; 16-30 years; 31-50 years and 51-88 years. The highest rates for positive samples were found in the 16-30 year group (76 and 79% by HI tests and ELISA respectively) as well as significant HI and ELISA geometric mean titres. Positive samples were less common in young children (46 and 50% by HI tests and ELISA respectively) and in the oldest group (44 and 54% respectively). The 31-50 years age group formed an intermediate class. The high prevalence of antibody as well as the significant titres indicate intense circulation of influenza C virus, especially among young adults. PMID- 1312565 TI - Repair of DNA damage induced in systemic lupus erythematosus skin fibroblasts by simulated sunlight. AB - Skin fibroblasts derived from three normal individuals and three patients exhibiting the disease systemic lupus erythematosus (SLE) were exposed to the simulated sunlight produced by a solar simulator. The induction and repair of DNA damage induced by this treatment were examined. The total number of lesions repaired by excision, as well as the removal of pyrimidine dimers and E. coli endonuclease III--sensitive sites did not differ significantly in the three SLE cell strains compared with normal cells. However, abnormalities in the formation and maintenance of DNA-protein crosslinks (DPC) and DNA single-strand breaks (SSB) were found in SLE-4 and SLE-5 following simulated sunlight exposure. In contrast, SLE-3 cells exhibited responses similar to normal cells in reference to SSB and DPC formation. These findings correlate well with the previously determined UV sensitivity of these SLE cell strains. PMID- 1312566 TI - Binding of beta-adrenergic receptors in human skin. AB - Radioligand-binding experiments were performed with crude membrane homogenates (CMH) from human skin in order to investigate the epidermal beta-adrenergic receptor (beta AR) density. CMH were prepared from leftovers of split-thickness skin grafts by sequential homogenization and centrifugation procedures to yield essentially epidermal fragments. Saturation experiments with the non-selective beta-adrenoceptor antagonist (-)-[125I]-iodocyanopindolol (ICYP) as radioligand showed saturable specific binding isotherms. Scatchard transformation of the data demonstrated high-affinity binding of ICYP to a single class of beta AR (Bmax = 80 +/- 10 fmol/mg protein; KD = 8 pM +/- 0.9; n = 8). beta AR antagonists displaced ICYP in a monophasic displacement pattern. The IC50 values were (nmol/1) propranolol (non-selective) 24.8; ICI 118,551 (beta 2 selective) 14.7; CGP-12177 (non-selective) 28.9; bisoprolol (beta 1 selective) 1500; CGP-20712A (beta 1 selective) 8990. beta AR agonists displaced ICYP with a potency ranking isoprenaline greater than adrenaline greater than noradrenaline. We conclude that epidermal crude membrane homogenates prepared from human split-thickness skin contain a high population of beta 2-adrenergic receptors. These receptors may be studied to further investigate the nature of human epidermal beta-adrenergic mechanisms. PMID- 1312567 TI - Heparan sulfate as a mediator of herpes simplex virus binding to basement membrane. AB - Explants of human lip and oral mucosa were infected with herpes simplex virus (HSV) in vitro and the expression of viral antigen was investigated by immunofluorescent antibody staining. Viral antigen was demonstrated in the cells of basal cell layer and lower prickle cell layers. Moreover, an accumulation of viral antigen in the epithelial-mesenchymal junction was observed. To examine the possibility that the basement membrane has an affinity for HSV, the interaction between HSV and major basement membrane components including type IV collagen, laminin, fibronectin, and heparan sulfate was investigated. When tested by a plaque-reduction assay, only heparan sulfate inhibited HSV plaque formation by competing for the virus adsorption to HEp-2 cells. The inhibitory effects of heparan sulfate and heparin were not affected by pre-incubation of these glycosaminoglycans with antithrombin III, whereas de-N-sulfation resulted in a significant reduction of their inhibitory activity. These findings suggest that heparan sulfate is involved in the binding of HSV to the basement membrane and that N-sulfated glucosamine residues of heparan sulfate are essential for HSV binding. The basement membrane may act as a reservoir of HSV in muco-cutaneous tissues. PMID- 1312568 TI - Encapsulation around malignant bone tumors after preoperative adjuvant treatment. AB - The effect of preoperative adjuvant treatment on encapsulation around the tumors was studied histologically in 16 patients with osteosarcoma and 2 patients with malignant fibrous histiocytoma of bone. The reactive zone in biopsy specimens was transformed into collagenous connective tissue after preoperative adjuvant treatment. The whole sections of specimens resected surgically from all 18 patients showed a thick capsule formation at the peri- and parosteal region of the tumors. However, no capsular structure was identified in the bone marrow. In skeletal muscles, the degree of encapsulation was correlated with the effect of preoperative adjuvant treatment. These results suggest that effective preoperative adjuvant treatment on malignant bone tumors clarifies the border between the tumors and the normal tissues in the extraosseous part, especially in the peri- and parosteal region. PMID- 1312569 TI - Insulin-like growth factor I receptor binding in brains of Alzheimer's and alcoholic patients. AB - Patients with chronic alcoholism and/or Alzheimer's disease show degenerative changes in the cerebral cortex and hippocampus. To investigate possible changes in insulin-like growth factor I receptor binding sites in brain tissue of patients with these pathological conditions, the number of 125I-insulin-like growth factor I binding sites was determined in tissues obtained from control patients and those with Alzheimer's and/or with a history of alcoholism. The four experimental groups examined consisted of patients from similar age groups. Postmortem histology and a clinical history were used for the diagnosis of Alzheimer's disease and alcoholism, respectively. Careful clinical records were kept concerning other variables such as immediate cause of death and medications administered before death. Specific binding of 125I-insulin-like growth factor I to homogenates prepared from cerebral cortex of Alzheimer's, alcoholic, alcoholic Alzheimer's, and age-matched control patients was similar, although Alzheimer's patients tended to have slightly higher binding values. No significant differences in insulin-like growth factor I binding in cerebral cortex were found with regard to age of patients, the interval between death and autopsy, and CNS active medications. No statistical differences in 125I-insulin-like growth factor I binding were noted in hippocampal tissue from the four patient groups. Thus, human insulin-like growth factor I binding sites in cerebral cortex and hippocampus appear unaffected by several variables. PMID- 1312570 TI - Characterization of the P-type and V-type ATPases of cholinergic synaptic vesicles and coupling of nucleotide hydrolysis to acetylcholine transport. AB - Both phosphointermediate- and vacuolar-type (P- and V-type, respectively) ATPase activities found in cholinergic synaptic vesicles isolated from electric organ are immunoprecipitated by a monoclonal antibody to the SV2 epitope characteristic of synaptic vesicles. The two activities can be distinguished by assay in the absence and presence of vanadate, an inhibitor of the P-type ATPase. Each ATPase has two overlapping activity maxima between pH 5.5 and 9.5 and is inhibited by fluoride and fluorescein isothiocyanate. The P-type ATPase hydrolyzes ATP and dATP best among common nucleotides, and activity is supported well by Mg2+, Mn2+, or Co2+ but not by Ca2+, Cd2+, or Zn2+. It is stimulated by hyposmotic lysis, detergent solubilization, and some mitochondrial uncouplers. Kinetic analysis revealed two Michaelis constants for MgATP of 28 microM and 3.1 mM, and the native enzyme is proposed to be a dimer of 110-kDa subunits. The V-type ATPase hydrolyzes all common nucleoside triphosphates, and Mg2+, Ca2+, Cd2+, Mn2+, and Zn2+ all support activity effectively. Active transport of acetylcholine (ACh) also is supported by various nucleoside triphosphates in the presence of Ca2+ or Mg2+, and the Km for MgATP is 170 microM. The V-type ATPase is stimulated by mitochondrial uncouplers, but only at concentrations significantly above those required to inhibit ACh active uptake. Kinetic analysis of the V-type ATPase revealed two Michaelis constants for MgATP of approximately 26 microM and 2.0 mM. The V-type ATPase and ACh active transport were inhibited by 84 and 160 pmol of bafilomycin A1/mg of vesicle protein, respectively, from which it is estimated that only one or two V-type ATPase proton pumps are present per synaptic vesicle. The presence of presumably contaminating Na+,K(+)-ATPase in the synaptic vesicle preparation is demonstrated. PMID- 1312571 TI - Activation of protein kinase C suppresses the gamma-aminobutyric acidB receptor mediated inhibition of the vesicular release of noradrenaline and acetylcholine. AB - Modulation of the gamma-aminobutyric acidB (GABAB) receptor-mediated response by protein kinase C (PKC) was examined with regard to inhibition by stimulation of the GABAB receptor of stimulation-evoked release of noradrenaline (NA) from slices of cerebellar cortex and of acetylcholine (ACh) from strips of ileum. 12-O Tetradecanoylphorbol 13-acetate (TPA) potentiated the high K(+)-evoked Ca2+ dependent release of NA and ACh, but not the ouabain-evoked release, even in the presence of external Ca2+. The potentiating effect was antagonized by sphingosine, thereby suggesting that PKC participates in the exocytotic-vesicular release of neurotransmitters, but does not do so in case of a nonvesicular release. GABA inhibited the high K(+)-evoked release of NA and ACh, but not the ouabain-evoked Ca(2+)-independent release. The effect of GABA was mimicked by baclofen and was antagonized by phaclofen, thereby suggesting that stimulation of the GABAB receptor inhibits the vesicular but not the nonvesicular release of neurotransmitters. TPA suppressed the GABAB receptor-mediated inhibition of high K(+)-evoked release of NA and ACh. The effect of TPA was antagonized by sphingosine. These results indicate that stimulation of the GABAB receptor inhibits the stimulation-evoked Ca(2+)-dependent release of neurotransmitters and that activation of PKC suppresses the GABAB receptor-mediated response. PMID- 1312572 TI - Inhibition of protein kinase C restores Na+,K(+)-ATPase activity in sciatic nerve of diabetic mice. AB - We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na+,K(+)-ATPase activity in the sciatic nerve of alloxan induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na+,K(+)-ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na+,K(+)-ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4-9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half-life of approximately 1 h. PMID- 1312573 TI - Detection of mRNAs encoding distinct isoenzymes of type II calcium/calmodulin dependent protein kinase using the polymerase chain reaction. AB - A modification of the polymerase chain reaction (PCR) was used to amplify nucleotide sequences encoding the 50-kDa (alpha) or 58- to 60-kDa (beta',beta) subunits of a brain-specific type II calcium/calmodulin-dependent protein kinase (CaM kinase II). Rat brain RNA from different regions and at different postnatal ages was purified, and reverse transcriptase was used to produce cDNA templates. Oligonucleotide primer pairs flanking a unique sequence in the coding region of the beta',beta subunit-specific cDNA or a unique sequence in the 3' noncoding region of the alpha subunit-specific cDNA were used to amplify sequences encoding portions of these subunits by PCR. Adult rat forebrain contained approximately three times as much alpha subunit mRNA as beta',beta subunit mRNA, whereas adult rat cerebellum contained a molar ratio of 1 alpha: 5 beta',beta. Intermediate levels of alpha and beta',beta subunit mRNAs were observed in adult pons/medulla, and in 4- and 8-day neonatal forebrain. This amplification assay was also used to demonstrate the presence of alpha subunit mRNA in cerebellar granule cells and 4 day neonatal forebrain, which was reported to be undetectable by other methods. Cerebellar granule cells contained less alpha subunit RNA relative to whole cerebellum, suggesting that this cell type expresses an isoform of CaM kinase II containing less alpha subunit protein in the holoenzyme. The observed levels of subunit-specific mRNAs were shown to parallel the levels of expressed protein subunits, suggesting that expression of kinase isoforms is transcriptionally regulated. The data also indicate that the conditions used for amplification of CaM kinase II mRNAs are semiquantitative. PMID- 1312574 TI - Dopamine stimulates [3H]phorbol 12,13-dibutyrate binding in cultured striatal cells. AB - The effect of dopamine (DA) on the binding of [3H]phorbol 12,13-dibutyrate ([3H]PdBu) in cultured rat striatal cells was examined. DA maximally increased specific [3H]PdBu binding by 70 +/- 10%, an increase comparable to that observed with norepinephrine (NE). This finding suggests that DA activates protein kinase C in cultured striatal cells, because increases in [3H]PdBu binding reflect translocation of protein kinase C. Half-maximal stimulation was observed with 10( 6) M DA. The peak response was observed at 2-3 min after addition of 10(-4) M DA, but [3H]PdBu binding was still increased above basal at 30 min. DA was not acting via an adrenergic receptor. Prazosin (10(-6) M) blocked the response to NE, suggesting mediation by an alpha 1-adrenergic receptor, but had little effect on the response to DA. Conversely, the D1 receptor antagonist SCH-23390 (10(-6) M) blocked the response to DA, but only partially inhibited the response to NE. Morphine (10(-6) M) inhibited the response to DA by 46 +/- 14%, but did not affect significantly the response to NE. The DA effect on [3H]PdBu binding is apparently independent of the increase in cyclic AMP seen on D1 receptor activation. Forskolin, apomorphine, and the D1 agonist SKF-38393 all increased cyclic AMP in striatal cells, but were less effective than DA in stimulating [3H]PdBu binding. The D2 agonist quinpirole was ineffective in stimulating either cyclic AMP or [3H]PdBu binding. PMID- 1312575 TI - Solubilization and purification of an alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid binding protein from bovine brain. AB - alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) is a selective ligand for an excitatory amino acid receptor subtype in mammalian brain. We have solubilized an AMPA binding protein from bovine brain membranes with 1% Triton X 100 in 0.5 M phosphate buffer and 20% glycerol at 37 degrees C and purified the stable binding sites using a series of chromatographic steps. Scatchard analysis of the purified preparation showed a curvilinear plot with dissociation constants of 10.6 and 323 nM and Bmax values of 670 and 1,073 pmol/mg of protein for the high- and low-affinity sites, respectively. Inhibition constants for several excitatory amino acid analogues were similar to those obtained for other membrane and solubilized preparations. Gel filtration of the soluble AMPA binding protein showed a single peak of [3H]AMPA binding activity at Mr approximately 500,000. With sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified AMPA binding protein showed a single major band at Mr = 110,000. Previously, we have shown that a monoclonal antibody (KAR-B1) against a frog brain kainate binding protein selectively recognizes an unknown protein in mammalian brain migrating at Mr approximately 100,000. We now show that this antibody recognizes the major component of the purified AMPA binding protein, supporting a structural similarity between the frog brain kainate binding protein and the mammalian AMPA binding protein. PMID- 1312576 TI - Metabolism of guanine and guanine nucleotides in primary rat neuronal cultures. AB - The metabolic fate of guanine and of guanine ribonucleotides (GuRNs) in cultured rat neurons was studied using labeled guanine. 8-Aminoguanosine (8-AGuo), an inhibitor of purine nucleoside phosphorylase, was used to clarify the pathways of GMP degradation, and mycophenolic acid, an inhibitor of IMP dehydrogenase, was used to assess the flux from IMP to GMP and, indirectly, the activity of the guanine nucleotide cycle (GMP----IMP----XMP----GMP). The main metabolic fate of guanine in the neurons was deamination to xanthine, but significant incorporation of guanine into GuRNs, at a rate of approximately 8.5-13.1% of that of the deamination, was also demonstrated. The turnover rate of GuRNs was fast (loss of 80% of the radioactivity of the prelabeled pool in 22 h), reflecting synthesis of nucleic acids (32.8% of the loss in radioactivity) and degradation to xanthine, guanine, hypoxanthine, guanosine, and inosine (49.3, 4.3, 4.1, 1.1, and 0.5% of the loss, respectively). Of the radioactivity in GuRNs, 7.9% was shifted to adenine nucleotides. The accumulation of label in xanthine indicates (in the absence of xanthine oxidase) that the main degradative pathway from GMP is that to xanthine through guanosine and guanine. The use of 8-AGuo confirmed this pathway but indicated the operation of an additional, relatively slower degradative pathway, that from GMP through IMP to inosine and hypoxanthine. Hypoxanthine was incorporated mainly into adenine nucleotide (91.5%), but a significant proportion (6%) was found in GuRNs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312577 TI - Kainic acid-induced decrease in hippocampal corticosteroid receptors. AB - The potential role of excitatory amino acids in the regulation of brain corticosteroid receptors was examined using systemic administration of kainic acid. Administration of kainic acid (5, 10, and 15 mg/kg) to 24-h adrenalectomized rats that were killed 3 h later produced large, dose-related decreases in glucocorticoid receptors (GR) in hippocampus (23-63%), frontal cortex (22-76%), and striatum (41-49%). Kainic acid did not decrease hypothalamic GR. Hippocampal mineralocorticoid receptors (MR) were also markedly decreased (50 71%) by kainic acid. Significant decreases in corticosteroid receptors could be detected as soon as 1 h after kainic acid (10 mg/kg) administration. Decreases in hippocampal, cortical, and hypothalamic GR as well as hippocampal MR were observed 24 h after administration of kainic acid (10 mg/kg) to adrenalectomized rats. Kainic acid (10 mg/kg) also significantly decreased hippocampal GR and MR as well as GR in the other three brain regions when administered to adrenal intact rats that were subsequently adrenalectomized and killed 48 h after drug administration. The kainic acid-induced decreases in hippocampal GR and MR binding were due to decreases in the maximum number of binding sites (Bmax) with no change in the apparent affinity (KD). Kainic acid when added in vitro did not displace the GR and MR radioligands from their respective receptors. These studies demonstrate that excitatory amino acids play a prominent role in the regulation of hippocampal corticosteroid receptors. In addition, the data indicate that noncorticosterone factors are involved in corticosteroid receptor plasticity. PMID- 1312578 TI - Acute and chronic ethanol exposure alters the function of hippocampal kainate receptors expressed in Xenopus oocytes. AB - The effects of acute and extended ethanol exposure on N-methyl-D-aspartate- and kainate-induced currents were examined electrophysiologically in Xenopus oocytes expressing rat hippocampal mRNA. Ethanol inhibited responses stimulated by low and high concentrations of N-methyl-D-aspartate to a similar degree. However, responses produced by low or high concentrations of kainate were differentially inhibited by ethanol. Low kainate concentration responses were much more sensitive to ethanol than high kainate concentrations (e.g., 50 mM ethanol inhibited 12.5 microM kainate responses by 45% compared to 15% inhibition of 400 microM kainate responses). In oocytes cultured in 100 mM ethanol for 1-5 days, the ethanol inhibition of maximum N-methyl-D-aspartate and kainate responses was not different from that in non-ethanol-exposed oocytes. Ethanol treatment, however, selectively decreased the ethanol sensitivity of low kainate concentration responses. Currents stimulated by N-methyl-D-aspartate or kainate were not different between control and ethanol-treated oocytes, indicating that ethanol exposure did not interfere with channel expression. The selective actions of acute and extended ethanol exposure on low kainate responses may indicate selective actions of ethanol on subtypes of kainate receptors expressed in oocytes. PMID- 1312579 TI - Changes in corticospinal facilitation of lower limb spinal motor neurons after spinal cord lesions. AB - The projections from the cortex to the motor neurons of lower limb muscles were examined in 33 normal subjects and 16 patients with incomplete spinal cord lesions. Corticospinal neurons were excited by transcranial magnetic stimulation and the effects on single spinal motor neurons determined from peristimulus time histograms (PSTHs) of single tibialis anterior (TA) and soleus (SOL) motor units. In normal subjects magnetic stimulation produced a short latency facilitation of TA motor units but had little or no effect on SOL motor units. In the patients with spinal cord lesions magnetic stimulation also produced facilitation of TA but not SOL motor units; however, the mean latency of the TA facilitation was significantly longer (by about 14 ms) in the patient group. The F wave latencies were normal in all patients tested, suggesting that central rather than peripheral conduction was slowed. The duration of the period of increased firing probability (in TA motor units) was also significantly longer in the patients with spinal cord lesions. These changes may reflect the slowing of conduction and dispersal of conduction velocities in the corticospinal pathways as a consequence of the spinal cord lesion. No significant correlations were found between the delay of the TA facilitation and the clinical deficits in this group of patients. PMID- 1312580 TI - Electrophysiological studies in cerebrotendinous xanthomatosis. AB - Seven patients with cerebrotendinous xanthomatosis (CTX) were studied by electrophysiological techniques. The percentages of abnormalities detected in nerve conduction studies and electroencephalograms were 28.6% (two patients) and 100%, respectively. All patients showed prolonged central conduction times in short latency somatosensory evoked potentials (SSEPs) by tibial nerve stimulation but normal SSEPs by median nerve stimulation. Brain stem auditory evoked potentials and visual evoked potentials were abnormal in three (42.9%) and four patients (57.1%), respectively. These electrophysiological parameters were correlated with the ratio of serum cholestanol to cholesterol concentration. The results of SSEPs suggest that the polyneuropathy in CTX is caused by distal axonopathy affecting longer axons before shorter axons (central-peripheral distal axonopathy). PMID- 1312581 TI - Weighted needle pinprick sensory thresholds: a simple test of sensory function in diabetic peripheral neuropathy. AB - A simple device is described, consisting of 12 weighted 23 gauge disposable needles (0.2 to 5.2 g), for testing sensation in busy diabetic clinics. The pinprick sensory threshold (PPT) is the lightest weighted needle which consistently elicits a sharp sensation. The subjects were 48 healthy controls (hospital staff), 44 diabetic patients without neuropathic symptoms, and 35 diabetic patients with chronic painful neuropathy. In the controls, the mean PPT from the right hand and foot obtained on two test occasions a week apart did not differ significantly. In diabetic patients without symptomatic neuropathy, the mean PPT in the right hand and right foot were significantly higher than in the controls. The diabetic patients with painful neuropathy had clearly increased mean PPT in the right hand and foot compared with controls. Marstock thermal limen in diabetic patients with painful neuropathy correlated significantly with PPT determinations. PPT and thermal thresholds probably give comparable information on small fibre dysfunction in diabetic patients with symptomatic neuropathy. Compared with thermal threshold determinations however, the weighted needle apparatus is inexpensive, simple, and rapid to use. PMID- 1312582 TI - The tarsal tunnel syndrome after a proximal lesion. AB - Three patients in whom the first symptoms of the tarsal tunnel syndrome (TTS) emerged after an acute event proximal to but not affecting the ankle are described. These patients suggest that a pre-existing asymptomatic TTS may become manifest after a mechanism akin to that described in the "double crush" syndrome. PMID- 1312583 TI - The differentiation of peripheral effector neuron failure from acute brain stem dysfunction in a critically ill patient. AB - A patient appeared to be in coma following pneumococcal meningitis, an intracerebral haemorrhage, and a cardiac arrest. Late in the course of his illness neurophysiological investigations confirmed a proposal that he also had a fulminant acute demyelinating polyneuropathy which, for a period of five days, rendered the patient completely unresponsive. The patient recovered and is now working without any disability. PMID- 1312584 TI - High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol. AB - PURPOSE: A phase II trial was undertaken to assess the feasibility, toxicity, and efficacy of high-dose carboplatin and etoposide with autologous bone marrow transplantation in patients with relapsed or refractory germ cell tumors. PATIENTS AND METHODS: Forty patients with recurrent germ cell cancer received carboplatin 500 mg/m2 and etoposide 400 mg/m2 given at 7, 5, and 3 days before marrow infusion. Autologous marrow infusion (day 0) was accomplished using one half of the bone marrow harvested before chemotherapy. Patients who achieved a complete or partial response with the first cycle of treatment received a second identical cycle of chemotherapy followed by infusion of the remaining cryopreserved bone marrow. RESULTS: Objective responses were obtained in 17 of the 38 patients (45%) assessable for response, including eight partial and nine complete remissions. Five of these patients remain in continuous complete remission with minimal follow-up of 1 year. Toxicity encountered was primarily hematologic, and five patients (13%) died of treatment-related complications. Significant toxicities often seen with high-dose cisplatin (ototoxicity, neurotoxicity, and renal toxicity) were manageable in this regimen of high-dose carboplatin. CONCLUSIONS: This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer. PMID- 1312585 TI - Surveillance after orchidectomy for patients with clinical stage I nonseminomatous testis tumors. AB - PURPOSE: This study was designed to determine the proportion of patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) managed with surveillance after orchidectomy who have more advanced disease and, therefore, require further treatment, the time to progression, the sites of progression, and the efficacy of treatment delayed until progression was recognized. PATIENTS AND METHODS: One hundred five patients were observed prospectively without further treatment after orchidectomy and full clinical staging. Treatment was given immediately upon detection of marker-positive, clinical, or radiologic evidence of disease. RESULTS: Thirty-seven patients (35.2%) have required further therapy for disease progression, occurring from 2 to 21 months after diagnosis. Thirty-six patients have been successfully treated. Overall, 104 patients (99%) remain alive and free of disease at 12 to 121 months after orchidectomy. Progression occurred in the retroperitoneum in 25 of 37 patients who developed further disease on surveillance. The presence of vascular invasion in the primary tumor was predictive of an increased risk of progression. CONCLUSION: Surveillance is a valid alternative to immediate retroperitoneal lymph node dissection in patients with clinical stage I NSGCTT but should be recommended only under the close supervision of physicians experienced in the diagnosis and treatment of testicular cancer. PMID- 1312586 TI - Is postchemotherapy retroperitoneal surgery necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses? AB - PURPOSE: At least one third of the patients with metastatic testicular cancer are rendered tumor-free by cisplatin-based chemotherapy. One may question, therefore, the routine use of postchemotherapy retroperitoneal lymph node dissection (RLND), especially if the residual masses are less than 20 mm in diameter. To define the role of such surgery, we analyzed the postchemotherapy histology in testicular cancer patients with minimal residual disease. PATIENTS AND METHODS: Seventy eight patients with advanced nonseminomatous testicular cancer underwent RLND after three to four cycles of cisplatin- or carboplatin-based chemotherapy. In all patients, the largest diameter of the residual retroperitoneal mass was less than 20 mm. RESULTS: Complete fibrosis/necrosis was found in 51 patients, mature teratoma in 22, and vital malignant germ cell tumor in five. In two of the latter five patients, alphafetoprotein (AFP) had increased immediately before RLND. In the 76 patients with normal pre-RLND tumor markers, the presence of undifferentiated malignant teratoma (MTU) in the primary tumor and normal prechemotherapy tumor markers were independent parameters predicting complete fibrosis/necrosis, which was demonstrated in all 15 patients with these two pretreatment parameters. CONCLUSIONS: Postchemotherapy RLND can be omitted in patients with MTU in the primary tumor who have normal AFP/human chorionic gonadotropin (AFP/HCG) before chemotherapy and whose residual retroperitoneal mass is less than 20 mm in diameter. If the pre-RLND tumor markers are normal, RLND should be performed in all other patients with small residual masses, even in the presence of a normal computed tomography (CT) and particularly if regular follow-up of the patients is not guaranteed. PMID- 1312587 TI - Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage III unresectable non-small-cell lung cancer: results of the Toronto Phase II Trial. AB - PURPOSE: The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer (NSCLC) are less than 10%. A pilot study of mitomycin, vindesine, and cisplatin (MVP) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients. PATIENTS AND METHODS: Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP. Responding patients underwent thoracotomy for resection and two further courses of MVP. RESULTS: The overall response rate was 64% (25 of 39) with three complete and 22 partial responses. Twenty-two patients were resected, which included a radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no tumor remaining. Toxicity included two postoperative deaths secondary to a bronchopleural (BP) fistula, mitomycin pulmonary toxicity in two patients, and septic deaths in four patients. Twenty-eight patients have died; 20 have recurrent or progressive disease. Eight of the 18 patients completely resected have recurred, with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain), and one in both. Median survival of all 39 patients is 18.6 months, with a 3-year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%. CONCLUSIONS: We conclude (1) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC; (2) the median survival seems to be prolonged; and (3) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III randomized trial to compare it with other treatment modalities. PMID- 1312588 TI - Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. AB - PURPOSE: A phase I and pharmacologic study was undertaken to determine the maximum-tolerated dose (MTD), describe the principal toxicities, and characterize the pharmacologic behavior of topotecan, which is a semisynthetic analog of camptothecin with broad preclinical antitumor activity and the first topoisomerase I-targeting agent to enter clinical development in the United States since studies of sodium camptothecin over 2 decades ago. PATIENTS AND METHODS: Thirty-minute infusions of topotecan were administered daily for 5 consecutive days every 3 weeks to patients with advanced solid malignancies at doses ranging from 0.5 to 2.5 mg/m2/d. RESULTS: At doses of 1.5 and 2.0 mg/m2, grade 3 and 4 neutropenia occurred in most courses; however, neutropenia was brief and rarely associated with fevers or treatment delays. Neutropenia was more severe in patients with extensive prior treatment than in minimally pretreated patients, but these differences were not substantial. At 2.5 mg/m2, topotecan induced profound and prolonged neutropenia that was frequently associated with fever and treatment delays in minimally pretreated patients. Topotecan also induced mild depressions in the hematocrit level in the majority of courses; however, precipitous drops requiring transfusional therapy occurred in 14% of courses and suggested a drug-induced hemolytic effect. Unlike sodium camptothecin, hemorrhagic cystitis was not observed. Thrombocytopenia, skin rash, diarrhea, and vomiting occurred infrequently and were modest in severity. Responses were observed in non-small-cell lung carcinoma and platinum-refractory ovarian carcinoma. Drug disposition in plasma was described by a biexponential model, with renal elimination accounting for 38.7% of drug disposition. Topotecan was rapidly hydrolyzed in vivo to a less active, open-ring form. CONCLUSIONS: Neutropenia is the dose-limiting toxicity, and 1.5 mg/m2 is the recommended starting dose of topotecan for both minimally and heavily pretreated patients in future phase II trials, with escalation to 2.0 mg/m2 if treatment is well tolerated. Non-small-cell lung and platinum-refractory ovarian carcinomas should be among those evaluated in phase II trials of topotecan. PMID- 1312589 TI - An integrated approach to the treatment of nicotine dependence in a medical center setting: description of the initial experience. AB - A nicotine-dependence treatment program can be implemented in a medical center setting by using a model that involves physician, patient, and nicotine dependence counselor. The physician-referred and counselor-directed consultations are followed by a systematic relapse-prevention program. The counselors utilize behavioral approaches, the philosophy and principles of the addictive disorders field, and adjunctive pharmacologic therapy. The patients are chronic, heavy smokers who have had many previous quit attempts and are highly nicotine dependent. Important factors include: 1) referral by physicians, 2) physicians' active role in the intervention, 3) expertise of the counselors, 4) structured relapse-prevention program, and 5) provision of services in a smoke-free medical center. PMID- 1312590 TI - Phagocytosis of Porphyromonas gingivalis and Prevotella intermedia by human polymorphonuclear leukocytes in clots formed from human plasma or purified fibrinogen. AB - We have studied the polymorphonuclear leukocyte (PMN) phagocytosis of Porphyromonas gingivalis (Bacteroides gingivalis) and Prevotella intermedia (Bacteroides intermedius) in three-dimensional fibrin meshworks formed by either clotting human plasma or by clotting purified fibrinogen with human serum incorporated. PMN phagocytosis of rhodamine isothiocyanate-labelled P. gingivalis in the fibrinogen clot was 43 +/- 6% and in the plasma clot was 62 +/- 10%; for P. intermedia the values were 15 +/- 10% and 63 +/- 10%, respectively. This showed that phagocytosis in the plasma clot system was significantly higher than in the fibrinogen clot system. However, increasing the concentration of serum in the fibrinogen clot abolished this difference, suggesting that opsonin levels determine PMN function in this assay. Labelling the bacteria with a different fluorochrome, fluoroscein isothiocyanate, reduced the level of PMN phagocytosis in both three-dimensional systems but phagocytosis was unaffected when PMN were adherent to glass. It would appear that PMN phagocytosis in three-dimensional systems can vary depending on the composition of the clot and the fluorochrome used to label the bacteria. PMID- 1312591 TI - A sensitive enzymatic method (SK-013) for detection and quantification of specific periodontopathogens. AB - Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola have been found to predominate in periodontal pockets of patients with adult periodontitis. These microorganisms hydrolyze the synthetic peptide N-benzoyl-DL arginine-2-naphthylamide (BANA). In this study, we developed an enzymatic method, designated SK-013, to detect the existence of these microorganisms in subgingival plaque bacteria. This enzymatic method was based on the observation of the hydrolysis of N-carbobenzoxy-glycyl-glycyl-arginyl-3,5-dibromo-4-hydroxyaniline (N-CBz-Gly-Gly-Arg-DBHA) and made more sensitive by adding an enhancing system. The SK-013 was specifically positive for P. gingivalis, B. forsythus, T. denticola, and some strains of Capnocytophaga species, but was not specific for any of the other bacterial strains tested. This SK-013 system may be valuable for detection and quantification of periodontal disease-associated bacteria in subgingival plaque and thus for diagnosis of periodontal infections. PMID- 1312592 TI - A sensitive enzymatic method (SK-013) for detection of Treponema denticola, Porphyromonas gingivals and Bacteroides forsythus in subgingival plaque samples. AB - An enzymatic method, SK-013, was developed for rapid detection of the peptidase activity in subgingival plaque samples. This method was found to have specificity for Porphyromonas gingivalis, Treponema denticola, Bacteroides forsythus, and some Capnocytophaga strains. The purpose of this study was to determine whether SK-013 could indicate the presence of periodontopathic bacteria, including T. denticola, P. gingivalis and B. forsythus, which produce trypsin-like enzymes. Subgingival plaque samples were taken from 10 clinically healthy sites and 30 periodontally diseased sites with 3 paper points. SK-013 activity of plaque samples was assayed, and the numbers of T. denticola, P. gingivalis and B. forsythus in the sample were counted by immunofluorescence technique. In diseased sites, the SK-013 activity was significantly correlated with clinical parameters such as Gingival Index, Plaque Index, probing depth and bleeding on probing. A significant correlation was found between the presence of these organisms and SK 013 activity. Correlation coefficients between the presence of T. denticola and SK-013 activity were higher than those with other organisms. These findings indicate that the SK-013 is useful as an indicator of cell population of T. denticola, P. gingivalis and B. forsythus in subgingival plaque. PMID- 1312593 TI - Utilization of genetic knowledge in pediatric nursing practice. AB - Many clients with potential genetic conditions are leaving clinics and hospitals without the conditions being recognized. Nurses knowledgeable in genetics can change this by using skills in genetic history-taking and dysmorphology assessment to recognize signs of genetic conditions and birth defects. Nurses can also positively impact clients' health by participating in follow-up care after a genetic evaluation and counseling. During any interaction, nurses need to be advocates for genetic clients. PMID- 1312594 TI - Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire. AB - Because little was known about the prevalence of neurological complications of human immunodeficiency virus type 1 (HIV-1) infection in Africa, we conducted a cross-sectional study among consecutive admissions to the internal medicine wards of Mama Yemo Hospital in Kinshasa, Zaire. Of the 196 patients studied, 104 (53%) were HIV-1 seropositive, of whom 50 (48%) had stage 3 and 49 (47%) had stage 4 HIV-1 infection according to the provisional WHO staging criteria for HIV infection. Neuropsychiatric abnormalities were present in 43 (41%) of 104 HIV-1 seropositive patients. Of the HIV-1-seropositive patients, 9 (8.7%; 95% confidence interval, 4-16%) were diagnosed as having possible HIV-1-associated dementia complex, 1 (1%) as having possible HIV-1 myelopathy, and 3 (2.7%) as having possible HIV-1-associated minor cognitive/motor disorder. Definitive diagnoses could not be made because there were no facilities for neuroimaging and neuropathology. Meningitis caused by cryptococcus was diagnosed in six (5.6%) and by Mycobacterium avium in two (2%) of the HIV-1 seropositive patients. Acute onset hemiplegia, believed to be due to stroke, was present in four (4%) of the HIV-1-seropositive patients. The prevalence of other central nervous system opportunistic infections and mass lesions, especially toxoplasmic encephalitis, could not be assessed. In this population of Zairian inpatients, the prevalence of neurological complications of HIV-1 infection was similar to that observed in industrialized countries among patients with advanced HIV disease. PMID- 1312595 TI - Extended stability of ganciclovir for outpatient parenteral therapy for cytomegalovirus retinitis. AB - Cytomegalovirus retinitis in the human immunodeficiency virus-infected patient currently requires almost daily and lifelong parenteral ganciclovir therapy. Self preparation of ganciclovir is not an option in the majority of patients with decreased visual acuity or poor muscle coordination. Therefore, based on current stability data, patients usually receive a 5-day supply of reconstituted drug. This requirement is unfortunately associated with poor patient compliance. If the extended stability of ganciclovir was known, then more efficient regimens for outpatient therapy could be formulated. This study was designed to determine the stability of reconstituted ganciclovir between 7 and 28 days. Ganciclovir diluted with normal saline or 5% dextrose in water to final drug concentrations of 5 or 10 mg/ml was evaluated for stability by high-pressure liquid chromatography under different conditions of storage. Samples were stored at both 4 degrees C and -20 degrees C in polyvinyl chloride bags and at 4 degrees C in ADFuse syringes. Ganciclovir remained stable under these conditions for 28 days. On the basis of these data, we have recommended that patients receive a 2-week supply of reconstituted ganciclovir for parenteral outpatient therapy. We have observed high levels of patient compliance with this regimen and no unexpected progression of retinitis over a 5-month period in three patients who received the drug in this fashion. PMID- 1312596 TI - The toxicity and local effects of the spermicide nonoxynol 9. PMID- 1312597 TI - The advantages of coated titanium implants prepared by radiofrequency sputtering from hydroxyapatite. AB - The method used to apply hydroxyapatite to implant surfaces may affect the thickness and ultimately the physical properties of the coating. This study investigated and compared the healing rates of bone around commercially pure titanium implants and titanium implants sputter-coated from a hydroxyapatite target. Forty-five sputter-coated implants and an equal number of noncoated titanium implants were placed into 15 partially edentulated dog mandibles. The implants were removed at three time periods and were evaluated mechanically and histologically. A multiple analysis of variance indicated that the interface bond strength was statistically greater (p less than 0.01) for the sputter-coated implants. Histologic analysis of the bone-implant interface demonstrated that coated implants had nearly twice the percentage of direct bone contact compared with noncoated implants. The results indicate that implants sputter-coated from a hydroxyapatite target will accelerate the healing of bone at the implant interface. PMID- 1312598 TI - Novel inhibitors of prolyl 4-hydroxylase. AB - A series of 5-acyl sulfonamides derived from pyridine-2,5-dicarboxylic acid (15) has been prepared and several members of this series have been shown to be more potent, in vitro, as inhibitors of prolyl 4-hydroxylase than 15. Several chain extended pyridinedicarboxylic acids have also been prepared and shown to be potent inhibitors of prolyl 4-hydroxylase. The structure-activity in both these series is discussed. The results indicate that the 5-carboxylic acid binding site, in the enzyme, can accept a carboxylic acid or an acyl sulfonamide equally well. This indicates a much greater degree of freedom in this distal carboxylic acid binding site than is predicted by the current theoretical model of the active site. PMID- 1312599 TI - Novel inhibitors of prolyl 4-hydroxylase. 2. 5-Amide substituted pyridine-2 carboxylic acids. AB - A series of 5-[(arylcarbonyl)amino]- and 5-(arylcarbamoyl)pyridine-2-carboxylic acids has been prepared and tested for activity as inhibitors of the enzyme prolyl 4-hydroxylase (EC 1.14.11.2). All the analogues prepared were inhibitors of the enzyme in vitro, the best compounds being equipotent with the known inhibitor pyridine-2,5-dicarboxylic acid (9). Like 9 these amidic analogues were not active in a cultured embryonic chick tendon cell model, considered to be a predictor of in vivo activity. The activity of the amides is not consistent with the model described for the mode of action of 9 with the enzyme and aspects of this are discussed. PMID- 1312600 TI - Antitumor agents. 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O demethylpodophyllotoxins. AB - The 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compounds are active as a result of the C-2' chloro substitution on ring E. This would suggest that the free rotation of ring E is essential for the aforementioned enzyme inhibitory activity. In addition, these 2'-chloro derivatives showed no significant cytotoxicity (KB). PMID- 1312601 TI - Antitumor agents. 124. New 4 beta-substituted aniline derivatives of 6,7-O,O demethylene-4'-O-demethylpodophyllotoxin and related compounds as potent inhibitors of human DNA topoisomerase II. AB - A series of 6,7-O,O-demethylene-4'-O-demethyl-4 beta-(substituted anilino)-4 desoxypodophyllotoxins (18-23), 6,7-O,O-demethylene-6,7-O,O-dimethyl-4'-O demethyl-4 beta-(substituted anilino)-4-desoxypodophyllotoxins (28-31), and their corresponding 4'-O-methyl analogues (12-17 and 24-27) have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 18-23 are 2-fold more potent than etoposide and compounds 12, 16, 17, 30, and 31 are as active as etoposide in their inhibition of the human DNA topoisomerase II. Compounds 19 and 20 and 29-31 are as active or more active than etoposide in causing protein-linked DNA breakage. These results indicate that a free C-4' hydroxy group is essential for the DNA breakage activity, and that the hydroxyl groups at C-6 and -7 positions may be involved in an interaction which is responsible for the inhibitory activity of DNA topoisomerase II. The maintenance of an intact methylene dioxy-type ring-A system would contribute to enhanced activity. In addition, the sterically less hindered substitution at C-6 and C-7 positions may be important for optimal interactions with DNA topoisomerase II. There is no correlation between the ability of these compounds to inhibit DNA topoisomerase II and their ability to cause protein-linked DNA breaks in cells. This may relate to the difference in uptake of these compounds. The better correlation was observed between the protein-linked DNA breaks and the cytotoxicity in KB cells of these compounds. PMID- 1312603 TI - Secondary metabolites by chemical screening. 17. Nigericinol derivatives: synthesis, biological activities, and modeling studies. AB - The synthesis and the biological activity of C-1-reduced nigericin derivatives (nigericinols) are described and discussed. The dichloronigericinol 7 impressively demonstrated that the C-1 carboxylic acid moiety was not required for a distinct activity against bacteria and viruses. Based on the correlation between K+/H+ antiport activities and antibacterial activities it was deduced that the mode of action of the described nigericinols are related to their ionophoric properties. Molecular modeling studies showed that the efficiency of the nigericinols as ionophores correlates, qualitatively, with the probability of forming a cyclic structure, with the exception of 7. PMID- 1312602 TI - Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure activity relationship of novel benzamides. AB - This report describes the development of novel benzamides which are orally active, highly potent, specific antagonists of 5-HT3 receptors. Described in this first report are the structure-activity relationships that led to novel structures with improved potency and selectivity. From this series of compounds, (S)-28 was identified and selected for further evaluation as a 5-HT3 receptor antagonist. Compared with 5-HT3 antagonists such as GR 38032F, BRL 43694, and metoclopramide, (S)-28 was most active in (a) inhibiting binding to 5-HT3 receptor binding sites in rat entorhinal cortex with an Ki value of 0.19 nM and (b) blocking cisplatin-induced emesis in the ferret with an ED50 value determined to be 9 micrograms/kg po. PMID- 1312604 TI - Changing the specificity of the sorting receptor for luminal endoplasmic reticulum proteins. AB - Luminal proteins of the endoplasmic reticulum (ER) share a common carboxy terminal tetrapeptide which is necessary and sufficient for their retention in the ER. In animal cells this retention signal is usually KDEL, whereas the yeast Kluyveromyces lactis uses the closely related sequences HDEL and DDEL. The yeast ERD2 gene has been shown to determine the capacity and specificity of the retention system, implying that it encodes a sorting receptor. This receptor is thought to retrieve escaped ER proteins from the Golgi, where a human homologue of this protein has been located. This dual function of binding and retrieval requires a receptor with highly specific binding at a specific location in the cell (Golgi but not ER). Here, a region of the ERD2 protein responsible for the specificity of ligand recognition has been identified using three independent approaches. A single amino acid residue is shown to selectively affect HDEL retention: substitution of residue 51 of the K. lactis receptor is sufficient to abolish recognition of HDEL but not DDEL, generating a novel retention phenotype. PMID- 1312605 TI - Regulation of open complex formation at the Escherichia coli galactose operon promoters. Simultaneous interaction of RNA polymerase, gal repressor and CAP/cAMP. AB - The regulation of open complex formation at the Escherichia coli galactose operon promoters by galactose repressor and catabolite activator protein/cyclic AMP (CAP/cAMP) was investigated in DNA-binding and kinetic experiments performed in vitro. We found that gal repressor and CAP/cAMP bind to the gal regulatory region independently, resulting in simultaneous occupancy of the two gal operators and the CAP/cAMP binding site. Both CAP/cAMP and gal repressor altered the partitioning of RNA polymerase between the two overlapping gal promoters. Open complexes formed in the absence of added regulatory proteins were partitioned between gal P1 and P2 with occupancies of 25% and 75%, respectively. CAP/cAMP caused open complexes to be formed nearly exclusively at P1 (98% occupancy). gal repressor caused a co-ordinated, but incomplete, switch in promoter partitioning from P1 to P2 in both the absence and presence of CAP/cAMP. We measured the kinetic constants governing open complex formation and decay at the gal promoters in the absence and presence of gal repressor and CAP/cAMP. CAP/cAMP had the largest effect on the kinetics of open complex formation, resulting in a 30-fold increase in the apparent binding constant. We conclude that the regulation of open complex formation at the gal promoters does not result from competition between gal repressor, CAP/cAMP and RNA polymerase for binding at the gal operon regulatory region, but instead results from the interactions of the three proteins during the formation of a nucleoprotein complex on the gal DNA fragment. Finally, we present a kinetic model for the regulation of open complex formation at the gal operon. PMID- 1312606 TI - Computer simulation of the initial proton transfer step in human carbonic anhydrase I. AB - The initial water proteolysis step in the proton transfer "half-reaction" of human carbonic anhydrase I is simulated using the empirical valence bond method in combination with free energy perturbation molecular dynamics calculations. A free energy profile for the enzyme catalysed reaction and the corresponding pKa associated with ionization of the zinc-bound water is calculated. The obtained pKa value of 7 to 8 appears to be in good agreement with experimental observations and the calculated rate constant for this step is also compatible with kinetic data. The simulations clearly emphasize the important electrostatic effect associated with the catalytic zinc ion. PMID- 1312607 TI - Protective immune response against foot-and-mouth disease. AB - The causative agents of foot-and-mouth disease (FMD) are small icosahedral viruses of the Aphthovirus group within the Picornaviridae family. There is no evidence that these viruses infect cells of the immune system or otherwise interfere detrimentally with their function; additionally, it has not been possible to relate cytotoxicity reactions against virus-infected cells to the efficacy of the immune response against FMD virus infection. In contrast, there is a close association between FMD virus antibody and the protective immune response (10, 14, 15, 20, 24, 25, 29-32). Induction of this antibody is dependent on the structure of the viral antigenic sites (7-9, 11, 18) and on the concomitant presence of Th-lymphocyte epitopes (4, 5, 7, 8), although a Th lymphocyte-independent response has been reported (2). Recent work by Piatti et al. (26) showed that the immune response induced by FMD virus was only Th lymphocyte dependent when low doses of antigen were used. This latter work was performed in mice, and it is not certain that a similar situation would be found in cattle. As for the major effector immune defense, this relies on the interaction between antibody-virus complexes and the phagocytic cells of the reticuloendothelial system (17, 19). PMID- 1312608 TI - Repair and mutagenesis of the genome of a deletion mutant of the coronavirus mouse hepatitis virus by targeted RNA recombination. AB - The genetic characterization of a nucleocapsid (N) protein mutant of the coronavirus mouse hepatitis virus (MHV) is described. The mutant, Albany 4 (Alb4), is both temperature sensitive and thermolabile. Analysis of the progeny of a mixed infection showed that the defective Alb4 allele is recessive to wild type, and its gene product is diffusible. The N protein of Alb4 was found to be smaller than its wild-type counterpart, and sequence analysis of the Alb4 N gene revealed that it contains an internal deletion of 87 nucleotides, producing an in frame deletion of 29 amino acids. All of these properties of Alb4 made it ideal for use as a recipient in a targeted RNA recombination experiment in which the deletion in Alb4 was repaired by recombination with synthetic RNA7, the smallest MHV subgenomic mRNA. Progeny from a cotransfection of Alb4 genomic RNA and synthetic RNA7 were selected for thermal stability. Polymerase chain reaction analysis of candidate recombinants showed that they had regained the material that is deleted in the Alb4 mutant. They also had acquired a five-nucleotide insertion in the 3' untranslated region, which had been incorporated into the synthetic RNA7 as a molecular tag. The presence of the tag was directly verified, as well, by sequencing the genomic RNA of purified recombinant viruses. This provided a clear genetic proof that the Alb4 phenotype was due to the observed deletion in the N gene. In addition, these results demonstrated that it is possible to obtain stable, independently replicating progeny from recombination between coronavirus genomic RNA and a tailored, synthetic RNA species. PMID- 1312609 TI - Mutations in the SH3 domain of the src oncogene which decrease association of phosphatidylinositol 3'-kinase activity with pp60v-src and alter cellular morphology. AB - To analyze the signaling pathways utilized in malignant transformation by pp60v src, we have isolated and characterized src mutants which possess normal levels of protein tyrosine kinase activity but which cause only a partially transformed phenotype. Our hypothesis is that such mutants are partially defective for transformation because they are defective in their ability to activate specific components of the cellular signaling machinery while still activating others. In this communication, we report on the molecular and biochemical characterization of one such mutant, CU12 (D. D. Anderson, R. P. Beckmann, E. H. Harms, K. Nakamura, and M. J. Weber, J. Virol. 37:455-458, 1981). Cells infected with this mutant are capable of anchorage-independent growth, but rather than exhibiting the rounded and refractile morphology characteristic of wild-type-infected cells, they display an extremely elongated, fusiform morphology. The morphological properties of this mutant src could be accounted for entirely by a single mutation in the SH3 domain (lysine 106 to glutamate). Other mutations were constructed in this region by in vitro mutagenesis, both in a v-src and in an activated c-src background, and several of them also induced a fusiform morphology. All of the mutations inducing fusiform morphology also resulted in decreased association of pp60src with phosphatidylinositol 3'-kinase activity. In addition, association of pp60src with some tyrosine-phosphorylated proteins was altered. We propose that the SH3 domain participates (along with the SH2 domain) in the interaction of pp60src with cellular signaling proteins, and we speculate that the association with phosphatidylinositol 3'-kinase plays an important role in the regulation of cellular morphology. PMID- 1312611 TI - The sequence context of the initiation codon in the encephalomyocarditis virus leader modulates efficiency of internal translation initiation. AB - Translation initiation on poliovirus and encephalomyocarditis virus (EMCV) mRNAs occurs by a cap-independent mechanism utilizing an internal ribosomal entry site (IRES). However, no unifying mechanism for AUG initiation site selection has been proposed. Analysis of initiation of mRNAs translated in vitro has suggested that initiation of poliovirus mRNA translation likely involves both internal binding of ribosomes and scanning to the first AUG which is in a favorable context for initiation. In contrast, internal initiation on EMCV mRNA may not utilize scanning, since ribosomes bind directly or very close to the initiation codon AUG 11. We have studied in vivo the sequence requirements for internal initiation around the EMCV initiation codon, both in monocistronic and in dicistronic mRNAs. Our studies show that the upstream AUG-10 is normally not used and that there is no specific sequence requirement for nucleotides between AUG-10 and AUG-11. However, the sequence context of AUG-11 does influence the efficiency of initiation at AUG-11. Efficient IRES-mediated internal initiation at AUG-11 exhibits a requirement for an adenine in the -3 position, similar to cap dependent initiation. These results support a model for internal initiation on EMCV mRNA in which scanning starts at or near AUG-11. Although initiation primarily occurs at AUG-11, initiation at multiple downstream AUG codons can be detected. In addition, a poor sequence context around AUG-11 results in increased initiation at one or more downstream AUG codons, indicative of leaky scanning or jumping by the ribosome from AUG-11 mediated by the EMCV IRES. PMID- 1312610 TI - BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication in vitro. AB - The Epstein-Barr virus (EBV) genome contains an open reading frame, BHRF1, that encodes a presumptive membrane protein with sequence similarity to the proto oncogene bcl2, which is linked to human B-cell follicular lymphoma. Potential roles for BHRF1 in EBV's ability to growth transform human B cells and to replicate in B cells in culture were investigated by generating EBV mutants that lack most of the open reading frame. This was accomplished by recombination of plasmids carrying mutations in BHRF1 with the transformation-defective EBV strain P3HR1. Because BHRF1 resides close to the deletion in P3HR1 that renders this strain transformation defective, B-cell transformation could be used to select for recombination events in the region. B-cell clones were established by recombinants which lacked most of the BHRF1 open reading frame, although most of these initial B-cell transformants also carried nonrecombinant (BHRF1+) P3HR1 genomes, at levels ranging from a fraction of a copy to four copies per cell. Secondary B-cell transformants that lacked BHRF1+ EBV at detectable levels were found to release transforming, BHRF1-deficient EBV at levels that were within the normal range for EBV-immortalized B-cell clones. These studies demonstrate that BHRF1 is nonessential for growth transformation of B cells and for virus replication and release from these cells in culture. PMID- 1312612 TI - Spacing is crucial for coordination of domain functions within the simian virus 40 core origin of replication. AB - The simian virus 40 core origin of replication is composed of distinct domains that are bracketed by DNA spacers. We created a matched set of insertion mutations in spacer sites to study the spatial relationships among origin domains. Insertions larger than a single base pair severely inhibit replication regardless of the helical phasing between domains. Replication-defective mutations reduce T-antigen binding and T-antigen-induced KMnO4 modifications of DNA to various extents. Mutations in the early half of the origin reduce T antigen functions in the entire origin, whereas mutations in the late half reduce functions only in that half. Surprisingly, some mutations that severely inhibit DNA replication reduce T-antigen-induced melting and other structural changes within origin DNA to only a limited extent. In contrast, all replication defective origin mutations prevent T antigen from extending the primary replication bubble beyond the limits of the core origin of replication. We conclude, therefore, that T-antigen-induced events within the core origin must be spatially coordinated for conversion of T-antigen hexamers bound to the core origin into mobile helicase units. PMID- 1312613 TI - CArG, CCAAT, and CCAAT-like protein binding sites in avian retrovirus long terminal repeat enhancers. AB - A strong enhancer element is located within the long terminal repeats (LTRs) of exogenous, oncogenic avian retroviruses, such as Rous sarcoma virus (RSV) and the avian leukosis viruses. The LTRs of a second class of avian retroviruses, the endogenous viruses (evs), lack detectable enhancer function, a property that correlates with major sequence differences between the LTRs of these two virus groups. Despite this lack of independent enhancer activity, we previously identified sequences in ev LTRs that were able to functionally replace essential enhancer domains from the RSV enhancer with which they share limited sequence similarity. To identify candidate enhancer domains in ev LTRs that are functionally equivalent to those in RSV LTRs, we analyzed and compared ev and RSV LTR-specific DNA-protein interactions. Using this approach, we identified two candidate enhancer domains and one deficiency in ev LTRs. One of the proposed ev enhancer domains was identified as a CArG box, a motif also found upstream of several muscle-specific genes, and as the core sequence of the c-fos serum response element. The RSV LTR contains two CArG motifs, one at a previously identified site and one identified in this report at the same relative location as the ev CArG motif. A second factor binding site that interacts with a heat stable protein was also identified in ev LTRs and, contrary to previous suggestions, appears to be different from previously described exogenous virus enhancer binding proteins. Finally, a deficiency in factor binding was found within the one inverted CCAAT box in ev LTRs, affirming the importance of sequences that flank CCAAT motifs in factor binding and providing a candidate defect in the ev enhancer. PMID- 1312614 TI - Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands. AB - Cytomegalovirus (CMV), similar to other members of the Herpesviridae family, can establish both persistent and latent infections. Each of the CMVs that are found in many animal species replicates in the salivary gland, and oral secretion represents a source of horizontal transmission. Locally restricted replication characterizes the immunocompetent individual, whereas in the immunocompromised host, protean disease manifestations occur due to virus dissemination. The virus is cleared by immune surveillance, and CD8+ T lymphocytes play a major role. Remarkably, certain cell types of salivary gland tissues are exempt from CD8+ T lymphocyte control of murine CMV infection and require the activity of CD4+ T lymphocytes. The results presented here suggest that this activity is a function of Th1 cells. Neutralization of endogenous gamma interferon abrogated the antiviral activity of Th1 cells but not that of CD8+ T lymphocytes in other tissues. Neutralization of endogenous gamma interferon did not interfere with the induction of the cellular and humoral immune response but acted during the effector phase. Recombinant gamma interferon could not replace the function of Th1 cells in vivo and had limited direct antiviral activity in vitro. The results therefore suggest that gamma interferon represents one, but not the only, essential factor involved in salivary gland clearance, establishment of CMV latency, and, eventually, the control of horizontal transmission. PMID- 1312615 TI - Inhibition of poliovirus RNA synthesis by brefeldin A. AB - Brefeldin A (BFA), a fungal metabolite that blocks transport of newly synthesized proteins from the endoplasmic reticulum, was found to inhibit poliovirus replication 10(5)- to 10(6)-fold. BFA does not inhibit entry of poliovirus into the cell or translation of viral RNA. Poliovirus RNA synthesis, however, is completely inhibited by BFA. A specific class of membranous vesicles, with which the poliovirus replication complex is physically associated, is known to proliferate in poliovirus-infected cells. BFA may inhibit poliovirus replication by preventing the formation of these vesicles. PMID- 1312616 TI - v-Src enhances phosphorylation at Ser-282 of the Rous sarcoma virus integrase. AB - The Rous sarcoma virus (RSV) integrase (IN) and the beta polypeptide (beta) of the reverse transcriptase are posttranslationally modified by phosphorylation on Ser at amino acid position 282 of IN. When IN was immunoprecipitated from RSV (Prague A strain) virions, approximately 30 to 40% of the IN molecules were phosphorylated. When IN was immunoprecipitated from a v-src deletion mutant (delta Mst-A) of RSV or from avian myeloblastosis virus (AMV), the percentage of IN molecules that were phosphorylated was significantly reduced. This reduction in phosphorylation of IN between virions was verified by [35S]Met-[35S]Cys or 32P labeling of IN, followed by immunoprecipitation analysis using antisera directed to the amino or carboxyl terminus of IN. In delta Mst-A or AMV, a nonphosphorylated, slightly truncated (at the carboxyl terminus) polypeptide was the major species of IN. The enhanced phosphorylation of IN does not appear to be a general function of transformed cells, since enhanced phosphorylation was not detected in AMV derived from viremic chickens or from a v-src deletion mutant of RSV propagated in a chemically transformed quail cell line, QT6. From these data, we conclude that v-Src is necessary for efficient phosphorylation of IN and beta. PMID- 1312617 TI - Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators. AB - We examined the mechanism of Tat-mediated trans activation through competition experiments employing Tat proteins of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). EIAV Tat, as well as chimeric EIAV/HIV 1 Tat proteins, inhibited HIV-1 Tat-mediated trans activation in a cell-type dependent fashion. Furthermore, these proteins inhibited trans activation by Tat bacteriophage R17 coat protein chimeras. Inhibition resulted from competition between activation domains of effectors and competitors for a limiting cellular cofactor. The context in which competitor activation domains were expressed contributed to the extent of inhibition. In transfected cells, EIAV Tat and all chimeric competitors were located primarily in the cytoplasm, whereas HIV-1 Tat was primarily located in the nucleus. These data are consistent with a model for trans activation in which the activation domain of Tat associates with and conveys a cellular factor to the transcription complex via the trans-acting responsive element (TAR). PMID- 1312618 TI - Human antibodies recognize multiple distinct type-specific and cross-reactive regions of the minor capsid proteins of human papillomavirus types 6 and 11. AB - Human serum samples derived from a case-control study of patients with cervical carcinoma (n = 174) or condyloma acuminatum (n = 25) were tested for the presence of immunoglobulin G antibodies to human papillomavirus type 6 (HPV6) L2 and HPV11 L2 recombinant proteins in a Western immunoblot assay. Thirty-six samples (18%) were positive for HPV6 L2 antibodies alone, 25 (13%) were positive for HPV11 L2 antibodies alone, and 34 (17%) were positive for both HPV6 L2 and HPV11 L2 antibodies. Thirty samples that were positive for both antibodies were tested for the presence of HPV6-HPV11 L2 cross-reactive antibodies. Fifteen (50%) serum samples contained HPV6-HPV11 L2 cross-reactive antibodies, and 15 (50%) contained independent, type-specific HPV6 L2 and HPV11 L2 antibodies. Altogether, 82% of the HPV6 L2 and HPV11 L2 antibody reactivities were type specific and 18% were HPV6-HPV11 cross-reactive. There was no significant difference in the prevalence of antibody reactivities between samples from patients with cervical carcinoma and those with condyloma acuminatum. Deletion mapping identified five HPV6 L2 regions that reacted with HPV6 type-specific antibodies: 6U1 (amino acids [aa] 152 to 173), 6U2 (aa 175 to 191), 6U3 (aa 187 to 199), 6U4 (aa 201 to 217), and 6U5 (aa 351 to 367). Five HPV11 L2 regions that reacted with HPV11 type-specific antibodies were identified: 11U1 (aa 49 to 84), 11U2 (aa 147 to 162), 11U3 (aa 179 to 188), 11U4 (aa 180 to 200), and 11U5 (aa 355 to 367). Two HPV6-HPV11 cross reactive regions were identified: 6CR1 (HPV6 L2 aa 106 to 128)/11CR1 (HPV11 L2 aa 103 to 127) and 6CR2 (HPV6 L2 aa 187 to 199)/11CR2 (HPV11 L2 aa 180 to 200). PMID- 1312619 TI - Class I major histocompatibility proteins are an essential component of the simian virus 40 receptor. AB - The class I molecules encoded by the major histocompatibility complex (MHC) present endogenously synthesized antigenic peptide fragments to cytotoxic T lymphocytes. We show here that these proteins are an essential component of the cell surface receptor for simian virus 40 (SV40). First, SV40 binding to cells can be blocked by two monoclonal antibodies against class I human lymphocyte antigen (HLA) proteins but not by monoclonal antibodies specific for other cell surface proteins. Second, SV40 does not bind to cells of two different human lymphoblastoid cell lines which do not express surface class I MHC proteins because of genetic defects in the beta 2-microglobulin gene in one line and in the HLA complex in the other. Transfection of these cell lines with cloned genes for beta 2-microglobulin and HLA-B8, respectively, restored expression of their surface class I MHC proteins and resulted in concomitant SV40 binding. Finally, SV40 binds to purified HLA proteins in vitro and selectively binds to class I MHC proteins in a cell surface extract. PMID- 1312620 TI - Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind. AB - We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries--Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The small amount of divergence in any one geographic location and the lack of marked divergence between the Tanzanian and Brazilian African genome variants two centuries after their likely introduction into the New World suggest a very slow rate of viral evolution. The phylogenetic tree therefore probably represents a minimum of several centuries of evolution, if not an age equal to that of the respective human races. PMID- 1312621 TI - Effects of hydrostatic pressure on a membrane-enveloped virus: high immunogenicity of the pressure-inactivated virus. AB - A new approach to the preparation of antiviral vaccines relying on the inactivation of the virus particle by hydrostatic pressure is described. The enveloped virus vesicular stomatitis virus was utilized as a model; a pressure of 260 MPa applied for 12 h reduced infectivity by a factor of 10(4), and the antibodies against pressurized material were as effective as those against the intact virus when measured by their neutralization titer. Fluorescence measurements indicate that application of pressure results in perturbations of the particle interactions that permit binding of specific molecular probes. Electron microscopy showed that the membrane of the pressurized virus was partially preserved, presenting the spike pattern of the membrane G protein. Unlike the icosahedral viruses, dissociation into smaller particles was not observed, but a constant change in the morphology was the presence of a bulge in the surface of the pressurized virus, indicating a displacement of the capsid subunits, retained under the lipid and protein membrane. PMID- 1312622 TI - Random mutagenesis of the thymidine kinase gene of varicella-zoster virus. AB - To understand the relationship between the primary structure and function of varicella-zoster virus thymidine kinase (VZV TK; EC 2.7.1.21), we established rapid screening and phenotypic selection of mutant VZV TK genes in TK-deficient Escherichia coli C600 by using a constitutive pKK223-3 expression plasmid. In this screening system, mutant TK genes generated by random mutagenesis were identified by the sensitivity of E. coli-expressing VZV TKs to 5-bromo-2' deoxyuridine and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil. Twenty-four mutant clones with amino acid substitutions were isolated, and their nucleotide sequence and enzymatic activities were determined. Of the 24 clones, 20 had single amino acid substitutions, 2 clones had double amino acid substitutions, and 1 clone had triple amino acid substitutions. In 17 cases of single amino acid substitution, six mutations led to lost enzyme activity, and four of these six mutations centered in the ATP-binding site. The other 11 mutations resulted in reduction of both TK and thymidylate kinase activities or only thymidylate kinase activity and were located in scattered positions in the VZV TK gene, although 5 mutations showed a tendency to cluster in the region between positions 251 and 260. PMID- 1312623 TI - The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells. AB - Previous studies have shown that the E7 gene of human papillomavirus (HPV) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells (HFE) and that the efficiency was increased in cooperation with the respective E6 gene, whereas the HPV6 E6 or E7 gene was not active in HFE. To detect weak immortalizing activities of the HPV6 genes, cells were infected with recombinant retroviruses containing HPV genes, alone and in homologous and heterologous combinations. The HPV6 genes, alone or together (HPV6 E6 plus HPV6 E7), were not able to immortalize cells. However the HPV6 E6 gene, in concert with HPV16 E7, increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone. Interestingly, 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized, whereas neither gene alone was sufficient. Thus, the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16. Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture, resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer. Additionally, combinations of genes that immortalized HFE cells (HPV16 E6 plus HPV16 E7, HPV16 E6 plus HPV6 E7, and HPV6 E6 plus HPV16 E7) also stimulated proliferation. PMID- 1312624 TI - Three-dimensional structure of single-shelled bluetongue virus. AB - The three-dimensional structure of single-shelled bluetongue virus has been determined to a resolution of 3 nm by using electron cryomicroscopy and image processing techniques. The single-shelled virion has a diameter of 69 nm. The three-dimensional structure of the virion has icosahedral symmetry with a triangulation number of 13 in a left-handed configuration. The three-dimensional structure can be described in terms of two concentric layers of density surrounding a central core density. Two distinctive features of the outer layer are the 260 knobby capsomeres located at all the local and strict threefold axes and the aqueous channels located at all the five- and six-coordinated positions. These protrusions extend outward from an inner radius of 28 nm. They are interconnected out to a radius of 30 nm by saddle-shaped densities across the local and strict twofold axes. The aqueous channels surrounded by these capsomeres are about 8 nm wide at the outer surface and 8 nm deep. Some of these channels extend inward, penetrating the inner layer. These channels may provide pathways for transporting the metabolites and mRNA during the transcriptase activity of the particles. The inner layer is a featureless smooth bed of density except for the indentations in register with the channels of the outer layer. We propose that the 260 capsomeres in the outer layer are made up of trimers of the major protein, VP7, and that the inner layer is composed of the second major protein, VP3. The density in the central portion of the structure at a radius of less than 21 nm is likely due to the minor proteins and the genomic RNA. PMID- 1312625 TI - Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. AB - A rapid and physiologically relevant hyperthermia-based induction procedure has been utilized to develop an in vivo model of induced herpes simplex virus (HSV) reactivation in outbred Swiss Webster mice. This procedure was found to efficiently reactivate latent virus from both trigeminal and lumbosacral ganglia. Examination of the time between hyperthermia and virus production demonstrated that detectable levels of infectious virus were present in ganglia as soon as 14 h posttreatment, with peak percent recoveries at 24 h. These data indicated that the switch from latent to active viral gene transcription occurred rapidly following treatment. Immunohistochemical staining for HSV type 1 antigens revealed rare antigen-positive ganglionic neurons 24 h postinduction. HSV antigens were not detected in any other cell type, and lateral spread of the infection was not observed. This is the first report of the detection of HSV antigens in vivo following induced reactivation in the intact nervous system and demonstrates that the neuron is the site of infectious virus production. In addition, our data strongly suggest that at least some neurons in which HSV antigens are detected during reactivation do not survive. Because the temporal and spatial characteristics of HSV reactivation have been clearly defined, this model is uniquely suited for the molecular dissection of the reactivation process. PMID- 1312626 TI - Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency. AB - Defined herpes simplex virus type 1 (HSV-1) mutants KOS/1 and KOS/62 (positive and negative, respectively, for latency-associated transcripts [LATs]) express the Escherichia coli beta-galactosidase (beta-Gal) gene during latency. These mutants were employed to assess the functions of the latency-associated transcription unit on establishment and maintenance of and reactivation from the latent state. It was found that in the trigeminal ganglia, the frequencies of hyperthermia-induced reactivation of KOS/62 and an additional LATs- mutant (KOS/29) were reduced by at least 80%. Quantification of latently infected neurons expressing the beta-Gal gene revealed that the LATs- mutant KOS/62 established approximately 80% fewer latent infections in the trigeminal ganglia than did KOS/1 (LATs+). This reduction in establishment which is evident in the trigeminal ganglia could account for the reduced frequency of reactivation from this site. In striking contrast, both LATs- mutants reactivated with wild-type frequencies from lumbosacral ganglia. Quantification of beta-Gal-positive neurons at this site revealed that KOS/62 established as many as or more latent infections than the LATs+ virus, KOS/1. Colocalization of HSV antigen and beta Gal suggested that the decreased establishment by LATs- mutants in trigeminal ganglia was the result of inefficient viral shutoff. Thus, one function of the HSV-1 LATs transcription unit is to promote the establishment of latency in trigeminal but not lumbosacral ganglia. Such a function may be relevant to understanding the distinct clinical recurrent disease patterns of HSV-1 and HSV 2. PMID- 1312627 TI - A deletion in the simian virus 40 large T antigen impairs lytic replication in monkey cells in vivo but enhances DNA replication in vitro: new complementation function of T antigen. AB - We describe a new complementation function within the simian virus 40 (SV40) A gene. This function is required for viral DNA replication and virus production in vivo but, surprisingly, does not affect any of the intrinsic enzymatic functions of T antigen directly required for in vitro DNA replication. Other well characterized SV40 T-antigen mutants, whether expressed stably from integrated genomes or in cotransfection experiments, complement these mutants for in vivo DNA replication and plaque formation. These new SV40 mutants were isolated and cloned from human cells which stably carry the viral DNA. The alteration in the large-T-antigen gene was shown by marker rescue and nucleotide sequence analysis to be a deletion of 322 bp spanning the splice-donor site of the first exon, creating a 14-amino-acid deletion in the large T antigen. The mutant gene was expressed in H293 human cells from an adenovirus vector, and the protein was purified by immunoaffinity chromatography. The mutant protein directs greater levels of DNA replication in vitro than does the wild-type protein. Moreover, the mutant protein reduces the lag time for in vitro DNA synthesis and can be diluted to lower levels than wild-type T antigen and still promote good replication, which is in clear contrast to the in vivo situation. These biochemical features of the protein are independent of the source of the cellular replication factors (i.e., HeLa, H293, COS 7, or CV1 cells) and the cells from which the T antigens were purified. The mutant T antigen does not transform Rat-2 cells. Several different models which might reconcile the differences observed in vivo and in vitro are outlined. We propose that the function of T antigen affected prepares cells for SV40 replication by activation of a limiting cellular replication factor. Furthermore, a link between the induction of a cellular replication factor and transformation by SV40 is discussed. PMID- 1312628 TI - Antigenic structure of human hepatitis A virus defined by analysis of escape mutants selected against murine monoclonal antibodies. AB - We examined the antigenic structure of human hepatitis A virus (HAV) by characterizing a series of 21 murine monoclonal-antibody-resistant neutralization escape mutants derived from the HM175 virus strain. The escape phenotype of each mutant was associated with reduced antibody binding in radioimmunofocus assays. Neutralization escape mutations were identified at the Asp-70 and Gln-74 residues of the capsid protein VP3, as well as at Ser-102, Val-171, Ala-176, and Lys-221 of VP1. With the exception of the Lys-221 mutants, substantial cross-resistance was evident among escape mutants tested against a panel of 22 neutralizing monoclonal antibodies, suggesting that the involved residues contribute to epitopes composing a single antigenic site. As mutations at one or more of these residues conferred resistance to 20 of 22 murine antibodies, this site appears to be immunodominant in the mouse. However, multiple mutants selected independently against any one monoclonal antibody had mutations at only one or, at the most, two amino acid residues within the capsid proteins, confirming that there are multiple epitopes within this antigenic site and suggesting that single-amino acid residues contributing to these epitopes may play key roles in the binding of individual antibodies. A second, potentially independent antigenic site was identified by three escape mutants with different substitutions at Lys-221 of VP1. These mutants were resistant only to antibody H7C27, while H7C27 effectively neutralized all other escape mutants. These data support the existence of an immunodominant neutralization site in the antigenic structure of hepatitis A virus which involves residues of VP3 and VP1 and a second, potentially independent site involving residue 221 of VP1. PMID- 1312629 TI - A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH. AB - A glycoprotein encoded by the UL1 gene of herpes simplex virus type 1 (HSV-1) was detected in infected cells with antipeptide sera. The UL1 gene has previously been implicated in virus-induced cell fusion (S. Little and P. A. Schaffer, Virology 112:686-697, 1981). Two protein species, a 30-kDa precursor form and a 40-kDa mature form of the glycoprotein, both of which were modified with N-linked oligosaccharides, were observed. This novel glycoprotein is the 10th HSV-1 glycoprotein to be described and was named glycoprotein L (gL). A complex was formed between gL and gH, a glycoprotein known to be essential for entry of HSV-1 into cells and for virus-induced cell fusion. Previously, it had been reported that gH expressed in the absence of other viral proteins was antigenically abnormal, not processed, and not expressed at the cell surface (U.A. Gompels and A. C. Minson, J. Gen. Virol. 63:4744-4755, 1989; A. J. Forrester, V. Sullivan, A. Simmons, B. A. Blacklaws, G. L. Smith, A. A. Nash, and A. C. Minson, J. Gen. Virol. 72:369-375, 1991). However, gH coexpressed with gL by using vaccinia virus recombinants was antigenically normal, processed normally, and transported to the cell surface. Similarly, gL was dependent on gH for proper posttranslational processing and cell surface expression. These results suggest that it is a hetero oligomer of gH and gL which is incorporated into virions and transported to the cell surface and which acts during entry of virus into cells. PMID- 1312630 TI - VPg gene amplification correlates with infective particle formation in foot-and mouth disease virus. AB - In order to analyze the function of VPg amplification in aphthoviruses, we have undertaken the first mutational analysis of the repetitive VPg-coding region using an improved foot-and-mouth disease virus (FMDV) cDNA clone from which infective viral RNA was synthesized. A set of VPg mutants was constructed by site directed mutagenesis which includes different VPg deletion mutations, a VPg insertion mutation, and amino acid residue replacement mutations that interfere with binding of the VPg protein to the viral RNA and with its proteolytic processing. Our results revealed that an amazing flexibility in the number of VPgs is tolerated in FMDV. Optimal viability is given when three VPgs are encoded. Deletion as well as insertion of one VPg gene still resulted in infective particle production. Infective particle formation was observed as long as one VPg remained intact. No obvious differences in the individual VPg molecules with regard to their promoting viral RNA synthesis were observed, indicating that all three VPgs can act equally in FMDV replication. Mutant polyprotein processing was comparable to that of the wild-type virus. However, VPg mutants showed reduced viral RNA synthesis levels after infection. The levels of viral RNA synthesis and infective particle formation were found to correlate with the number of functional VPgs left in the mutant virus. These findings suggest a direct VPg gene dosage effect on viral RNA synthesis, with a secondary effect on infective particle formation. PMID- 1312631 TI - Identification of dominant-negative mutants of the herpes simplex virus type 1 immediate-early protein ICP0. AB - ICP0 is a 110,000-molecular-weight immediate-early protein of herpes simplex virus type 1 (HSV-1) which is encoded by three exons. It has been shown to function as a promiscuous transactivator of a variety of different HSV-1 and non HSV-1 promoters in transient expression assays. Analysis of mutations which truncated the carboxy-terminal end of this 775-amino-acid (aa) protein demonstrated that a polypeptide which contained only aa 1 to 553 still possessed significant transactivation potential. Additional carboxy-terminal truncations which sequentially removed aa 245 to 553 and thus the remainder of the third exon resulted in the eventual loss of transactivation capability in these mutants. However, further analysis of these truncated derivatives demonstrated that they behaved as dominant-negative mutants to the wild-type polypeptide. Moreover, one of the mutants was found to act as a promiscuous repressor, in that it could dramatically inhibit a variety of HSV-1 promoters, non-HSV-1 promoters, and heterologous transactivator proteins in transient expression assays, despite having lost almost the entire third exon. These results indicate that a domain encoded by the first two exons probably interacts with, and can effectively titrate, the unknown cellular factor(s) through which ICP0 mediates transactivation. PMID- 1312632 TI - Detection of receptor-specific murine leukemia virus binding to cells by immunofluorescence analysis. AB - Four classes of murine leukemia virus (MuLV) which display distinct cellular tropisms and bind to different retrovirus receptors to initiate virus infection have been described. In the present study, we describe a rapid, sensitive immunofluorescence assay useful for characterizing the initial binding of MuLV to cells. By using the rat monoclonal antibody 83A25 (L. H. Evans, R. P. Morrison, F. G. Malik, J. Portis, and W. J. Britt, J. Virol. 64:6176-6183, 1990), which recognizes an epitope of the envelope gp70 molecule common to the different classes of MuLV, it is possible to analyse the binding of ecotropic, amphotropic, or xenotropic MuLV by using only a single combination of primary and secondary antibodies. The MuLV binding detected by this assay is envelope receptor specific and matches the susceptibility to infection determined for cells from a variety of species. The binding of amphotropic MuLV to NIH 3T3 cells was shown to be rapid, saturable, and temperature dependent. Chinese hamster ovary (CHO-K1) cells normally lack the ability to bind ecotropic virus and are not infectible by ecotropic vectors. Expression of the cloned ecotropic retrovirus receptor gene (Rec) in CHO-K1 cells confers high levels of ecotropic virus-specific binding and confers susceptibility to infection. Characterization of MuLV binding to primary cells may provide insight into the infectibility of cells by retroviruses and aid in the selection of appropriate vectors for gene transfer experiments. PMID- 1312634 TI - The bovine papillomavirus constitutive enhancer is essential for viral transformation, DNA replication, and the maintenance of latency. AB - Bovine papillomavirus type 1 (BPV-1) has served as the prototype papillomavirus for the study of viral transcription, DNA replication, and latency. However, no cis essential transcription control regions which are necessary for both transformation and replication of BPV-1 or any other papillomavirus have yet been defined. We have found that BPV-1 mutants with deletions in the long control region were defective for transformation and replication, with the essential region in the 5' long control region corresponding to the previously defined BPV 1 constitutive enhancer (S. B. Vande Pol and P. M. Howley, J. Virol. 64:5420 5429, 1990). BPV-1 mutants deleted of the constitutive enhancer could be complemented in trans by the full-length virally encoded E2 transactivator and replication factor (E2TA) and in cis by the simian virus 40 enhancer. The constitutive enhancer induced the production of E2TA by activating all the major viral early promoters upstream of the E2 open reading frame. Complementation experiments using a temperature-sensitive E2TA mutant indicated that the constitutive enhancer was necessary for the maintenance of viral DNA replication within latently infected cells and implied that viral transcription under the regulation of the constitutive enhancer may be controlled during the cell cycle. The constitutive enhancer is a master regulatory control region for establishing and maintaining BPV-1 latency, and its characteristics reveal some analogies with cell type-specific enhancer elements recognized in the human papillomaviruses. PMID- 1312633 TI - Glycoprotein gI of pseudorabies virus promotes cell fusion and virus spread via direct cell-to-cell transmission. AB - Mutants of pseudorabies virus defective in either glycoprotein gI or gIII are only slightly less virulent for mice and chickens than is wild-type virus, while mutants defective in both gI and gIII are avirulent. To clarify the reason for the lack of virulence of the gI- gIII- mutants, we have analyzed in some detail the interactions of these mutants with their hosts. The results obtained showed that the gI glycoprotein is an accessory protein that promotes cell fusion. This conclusion is based on the findings that in some cell types, syncytium formation is significantly reduced in mutants deficient in gI. Furthermore, despite efficient replication, gI- mutants form significantly smaller plaques on some cell types. Finally, while wild-type and gI- virus are neutralized similarly by antisera, the size of the plaques formed by gI- mutants, but not by wild-type virus, is reduced by the presence of neutralizing antibodies in the overlay. Passive immunization of mice with neutralizing antipseudorabies virus sera is also considerably more effective in protecting them against challenge with gI- mutants than in protecting them against challenge with wild-type virus. These results show that gI- mutants are deficient in their ability to form syncytia and to spread directly by cell-to-cell transmission and that these mutants spread mainly by adsorption of released virus to uninfected cells. Wild-type virus and gIII- mutants, however, spread mainly via direct cell-to-cell transmission both in vivo and in vitro. We postulate that the lack of virulence of the gIII- gI- virus is attributable to its inability to spread by either mode, the defect in gIII affecting virus spread by adsorption of released virus and the defect in gI affecting cell-to-cell spread. Although a gI- gIII- mutant replicates as well as a gIII- mutant, it will be amplified much less well. Our results with in vitro systems show that this is indeed the case. PMID- 1312635 TI - Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus. AB - Murine AIDS (MAIDS) is readily induced by the Duplan strain of defective murine leukemia virus in susceptible C57BL/6 mice. To identify mouse strains resistant to MAIDS, and to understand the genetic factors controlling susceptibility to the disease, we screened more than 20 inbred strains of mice for their susceptibility to MAIDS. For this study, mice of the Fv-1n/n, Fv-1b/b, or Fv-1n/b genotype were inoculated with stocks of defective MAIDS virus pseudotyped with N-tropic, B tropic, or NB-tropic helper murine leukemia virus, respectively. Strains could be classified as susceptible, resistant, or moderately resistant. None of the individual H-2 haplotypes examined appears to explain resistance to MAIDS by itself. However, a very good correlation between the susceptibility or resistance phenotype and the presence or absence of defective proviral DNA and RNA in the spleen of these animals was found. Since the presence of defective proviral DNA and RNA reflects the oligoclonal proliferation of the cells infected by the defective MAIDS virus, our results strongly suggest that this target cell expansion is genetically controlled and is necessary and perhaps even sufficient for the development of the disease. PMID- 1312636 TI - An AP-1 binding site is the predominant cis-acting regulatory element in the 1.2 kilobase early RNA promoter of human cytomegalovirus. AB - To extend our analysis of the regulation of human cytomegalovirus (HCMV) early gene expression, we examined a transcription unit located in the terminal repeats of the long segment of the viral genome. This region encodes a major 1.2-kb RNA which is induced at early times in infection but undergoes its largest increase in abundance after the onset of viral DNA replication. To identify the important cis-acting regulatory elements for this gene, two constructs were prepared for use in transient expression assays. One contained 413 bp of the upstream sequence and 43 bp of the leader sequence fused to the gene for chloramphenicol acetyltransferase (CAT). The second construct included 1,722 bp upstream of the start site of the 1.2-kb RNA, the entire transcribed region with an additional 166-bp insert derived from the CAT gene as an assayable marker, and 2,393 bp downstream of the polyadenylation signal. Both constructs were individually transfected into human fibroblast cells, and the cells were infected with HCMV. RNA specified by the hybrid construct was initiated at the correct position and accumulated with the same kinetics as the authentic viral transcript at early times in the infection but did not undergo the increase in abundance at late at late times. By 5'-end-deletion analysis, we determined that the promoter for the 1.2-kb RNA contains a number of cis-acting elements, the most significant of which are the TATA-like sequence CATAAA at -30 and a sequence corresponding to the binding site for the transcription factor AP-1 at -75. Using extracts prepared from HeLa cells as well as from infected and uninfected fibroblasts in gel retardation assays, we obtained evidence for the specific interaction of a cellular factor(s) with the AP-1 binding site. The pattern of binding differed in the HeLa and fibroblast cells but did not change as a function of the HCMV infection. However, the functional importance of the AP-1 binding site and its key role in the regulation of the 1.2-kb RNA was supported by analysis of constructs containing specific point mutations at this site in gel retardation and transient expression assays. Site-specific mutations in the AP-1 consensus sequence, which resulted in the complete loss of binding to cellular factors, eliminated the basal activity and reduced the inducible promoter activity by eightfold. PMID- 1312637 TI - Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. AB - The E7 gene of human papillomavirus type 16 encodes a multifunctional nuclear phosphoprotein that is functionally and structurally similar to the adenovirus (Ad) E1A proteins and the T antigens of other papovaviruses. E7 can cooperate with an activated ras oncogene to transform primary rodent cells, trans activate the Ad E2 promoter, and abrogate transforming growth factor beta-mediated repression of c-myc. Recent studies suggest that these functions may in part be a consequence of the ability of E7 to associate with the product of the retinoblastoma tumor suppressor gene (pRB). In this study, a series of site specific mutations of the human papillomavirus type 16 E7 gene product were constructed and assessed for their effects on intracellular protein stability, ras cooperativity, transcriptional trans activation, pRB association, and phosphorylation. The results of these studies indicate that the transforming and trans-activating domains extensively overlap within a region of the protein analogous to conserved region 2 of Ad E1A, suggesting that pRB binding is necessary for both activities. Deletion of sequences in conserved region 1 abrogates cellular transformation but has only a marginal effect on trans activation. These data suggest that E7 trans activation and cellular transformation are interrelated but separable functions. PMID- 1312638 TI - Efficacy of oral administration of live herpes simplex virus type 1 as a vaccine. AB - Mice given herpes simplex virus type 1 (HSV-1) (Miyama +GC strain) intragastrically via a stainless-steel cannula were rendered immune to subsequent lethal intraperitoneal (i.p.) challenge with HSV-1. The orally administered HSV-1 was completely inactivated in the stomach within a few minutes of inoculation. However, systemic immunity was established 14 days after oral inoculation with the virus and retained for up to 6 months. The mechanisms of establishing systemic immunity were investigated by means of adoptive transfer comparisons. When splenic cells from HSV-1-immunized mice were transplanted into nonimmunized mice, all of the recipient mice survived after a lethal i.p. challenge with the virus. Immunity was not established in antithymocyte serum-treated mice or by transfer of serum from immunized to nonimmunized mice. In addition, all HSV-1 immunized mice died after lethal challenge with HSV-2 and influenza virus A. These findings suggest that the immunity was virus specific, with T lymphocytes playing a major role in its establishment. The present study therefore supports the possibility of oral immunization with live HSV-1 as a vaccine. PMID- 1312639 TI - Characterization of dexamethasone-induced reactivation of latent bovine herpesvirus 1. AB - Synchronous reactivation of bovine herpesvirus type 1 in all latently infected rabbits was achieved following a single intravenous dose of dexamethasone. Reactivated latent virus was first present in ocular secretions between 48 and 72 h post-dexamethasone treatment (PT). Cell-free infectious virus, viral-antigen containing neurons, and pathologic changes were detectable in trigeminal ganglia (TG) by 48 h PT. A shift from the viral transcriptional pattern characteristic of the latent state (latency-related RNA [LR RNA]) to one typical of that seen during acute infection was detected in a small number of neurons in latently infected TG between 15 and 18 h PT, with viral DNA first detectable by in situ hybridization at 18 to 21 h PT. The number of LR RNA-containing neurons in latently infected TG decreased significantly at 24 and 48 h PT but returned to near-normal levels by 72 h PT. Correlation of this decrease with viral reactivation suggests that altered regulation of LR RNA transcription is a significant event in the process of viral reactivation. PMID- 1312640 TI - Transformation by hamster polyomavirus: identification and functional analysis of the early genes. AB - A strategy involving polymerase chain reaction amplification of cDNAs was designed to study the expression of the hamster polyomavirus (HaPV) early region in HaPV-transformed rat fibroblasts, productively HaPV-infected cells, and HaPV induced lymphoma. We identified three mRNAs resulting from alternative splicing of open reading frames leading to coding capacities for three polypeptides with molecular weights similar to those of the murine polyomavirus large T, middle T (MT), and small T (ST) antigens. The corresponding intronless cDNAs direct the in vitro synthesis of polypeptides with the expected electrophoretic mobilities. The biological activities carried by the HaPV early genes were assayed by transfection of appropriate cell systems. The fragment of genomic viral DNA that encodes the three early antigens contains all of the genetic information necessary for immortalization of primary rat embryo fibroblasts and transformation of F111 rat cells. The large T antigen is sufficient for immortalization, although the MT and ST antigens stimulate the growth and modify the phenotype of immortal cell lines. A stringent cooperative effect was observed in the transformation of F111 cells, which requires the simultaneous presence of the MT and ST antigens, as opposed to the transformation by murine polyomavirus, which can be carried out by the MT antigen alone. PMID- 1312641 TI - A chimeric poliovirus/CD4 receptor confers susceptibility to poliovirus on mouse cells. AB - The human poliovirus receptor consists of three extracellular immunoglobulinlike domains, a transmembrane domain, and an intracytoplasmic domain. The amino terminal variable-type domain (V domain) of the human poliovirus receptor is necessary and sufficient for its function as a viral receptor (H.-C. Selinka, A. Zibert, and E. Wimmer, Proc. Natl. Acad. Sci. USA 88:3598-3602, 1991). In this paper, data are presented showing that transfer of the putative poliovirus receptor-binding domain to a truncated receptor for the human immunodeficiency virus results in a functional receptor for poliovirus. After expression in mouse cells, this chimeric protein confers susceptibility to poliovirus. Thus, unlike human immunodeficiency virus, poliovirus can enter mouse cells by way of a truncated CD4 receptor if the specific binding domain for poliovirus is provided. PMID- 1312642 TI - A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family. AB - By insertional mutagenesis, human cytomegalovirus recombinants deleted of each of the US6 glycoprotein family genes were isolated. A recombinant lacking IRS1, US1 through US5, and most of the US6 family was also isolated. The growth kinetics of these mutants were similar to that of the wild type. A dispensable cluster of genes was identified. PMID- 1312644 TI - Decline in maternal immunity and antibody response to vaccine in captive cheetah (Acinonyx jubatus) cubs. AB - Blood was collected from captive cheetah cubs (Acinonyx jubatus) from the ages of 4 to 12 wk and monitored for the decline in maternally derived antibodies to feline panleukopenia, herpes and calici viruses. A steady decrease was seen in most of the cubs. Antibody responses to inactivated and/or modified live virus (MLV) vaccine also were measured. The strongest responses were seen post vaccination with MLV vaccine only. PMID- 1312643 TI - Mouse mammary tumor gene int-3: a member of the notch gene family transforms mammary epithelial cells. AB - Expression of a 2.3-kb RNA species is induced in mammary tumors as a consequence of insertional mutagenesis at the int-3 locus by the mouse mammary tumor virus. The nucleotide sequence and biological activity of this mammary tumor-specific int-3 RNA species were determined. It contains an open reading frame which encodes a 57-kDa protein. The translated protein possesses six nearly contiguous 32-amino-acid repeats which are related to a similar motif in the Saccharomyces cerevisiae cdc-10-encoded cell cycle protein. In addition, the int-3 cdc-10 repeats are bounded by the PEST amino acid sequence motif which is commonly found in proteins having a rapid turnover and may represent sites for phosphorylation. The int-3 cdc-10 repeat sequences are 50% identical to a portion of the intracellular domain of the neurogenic Drosophila notch gene product. Activation of expression of a recombinant int-3 genomic DNA fragment encoding the 2.3-kb RNA species in HC11 mouse mammary epithelial cells in vitro induces anchorage independent growth in soft agar. PMID- 1312645 TI - Concomitant cryptosporidia, coronavirus and parvovirus infection in a raccoon (Procyon lotor). AB - A juvenile raccoon (Procyon lotor) was found moribund near Fort Collins, Colorado (USA). Upon examination, the raccoon was dehydrated, had a mucopurulent oculonasal discharge and diarrhea, and was euthanized. Postmortem examination revealed emaciation, severe fibrinous gastroenteritis and a small, firm liver. Histopathological findings included blunting of villi, infiltration of lamina propria with neutrophils and plasma cells, and mild bronchopneumonia. Cryptosporidium sp. was demonstrated on intestinal villi and coronavirus and parvovirus were identified in feces. Fluorescent antibody test for rabies was negative and no evidence of canine distemper was found. PMID- 1312646 TI - Antibodies to Ockelbo virus in three orders of birds (Anseriformes, Galliformes and Passeriformes) in Sweden. AB - Sera from 324 birds collected in an Ockelbo virus disease endemic area in central Sweden were examined for the presence of specific antibodies to Ockelbo virus by a plaque reduction neutralization test. Birds examined belonged to the orders Anseriformes (n = 207), Galliformes (n = 66) and Passeriformes (n = 51). Ockelbo virus neutralizing antibodies were detected in 26 (8%) of the specimens, including species from each of the three orders tested. Specific antibodies found in caged birds and in 6- to 10-week-old birds suggested local transmission. The highest antibody prevalence (27%, 14/51) was observed in the Passeriformes in which 5 of 9 species tested contained antibodies. The high antibody prevalence in passeriforms and the very large population of this group in relation to other avian groups in Sweden gives them a high potential as amplification hosts for Ockelbo virus. PMID- 1312647 TI - Reticuloendotheliosis in a wild turkey (Meleagris gallopavo) from coastal Georgia. AB - An emaciated wild turkey (Meleagris gallopavo) exhibiting neurologic signs was found on Ossabaw Island, Chatham County, Georgia (USA) on 11 April 1989. The neurologic abnormalities observed included ataxia, drooping wings, head tremors, torticollis, and circling. At necropsy, discrete yellowish-white nodules, varying in size from 2 to 5 mm, were present in the spleen. White nodular lesions approximately 2 mm in diameter were observed beneath the mucosal surface of the distal esophagus. Histopathologic examination of the splenic nodules disclosed large numbers of primitive lymphoreticular cells with leptochromatic nuclei and abundant, slightly basophilic cytoplasms. The mitotic index in these cells was moderate to high. Similar neoplastic cells composed the masses observed in the esophagus. Multifocal, mild perivascular cuffing with mononuclear cells was found in the lumbar spinal cord, brain, and brain stem. Reticuloendotheliosis virus, subtype 3, was isolated from samples of the spleen and liver. PMID- 1312648 TI - Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart. AB - The accumulation of both Inositol-(1,4,5)-trisphosphate (IP3) and Inositol (1,3,4,5)-tetrakisphosphate (IP4) after hormonal stimulation has a physiological role, possibly in altering Ca2+ levels in cardiac tissue. However, the accumulation of inositol polyphosphate under pathophysiological conditions has not been studied. In our experiments the metabolism of phatidylinositol and IP3 in cardiac myocytes as investigated. It was shown that basal levels of cytosolic phosphatidylinositol specific phospholipase C (PI-PLC), phosphatidylinositol (4,5)-bisphosphate specific phospholipase C (PIP2-PLC) activities markedly increased in stroke-prone spontaneously hypertensive rats (SHRSP) with age compared with age matched Wistar Kyoto rats (WKY). IP3 kinase and IP3 phosphatase activities also increased in SHRSP hearts with age. Their activities increased in WKY, but to a lesser extent than in SHRSPs. These data suggest that a PI turnover pathway such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway may have an important role in the development of hypertrophy in SHRSP heart. PMID- 1312649 TI - Viral genomic detection in the hearts of C3H/He mice with experimental Coxsackievirus B3 myocarditis by gene amplification using the polymerase chain reaction. AB - On the basis of the detection of the enteroviral RNA in the hearts of patients with healed myocarditis and dilated cardiomyopathy, we investigated cardiac viral persistence in experimental myocarditis. Weanling C3H/He mice were given myocarditis by inoculation with coxsackievirus B3 (Nancy strain), and their hearts were examined by genomic studies and viral isolation up to the 180th day after inoculation. The virus was isolated from the heart until the 9th day. By slot-blot hybridization, viral RNA was also only detected until the 9th day in the heart. Specific DNA amplification using the polymerase chain reaction (PCR) was performed after a reverse transcriptase reaction, then followed by Southern blot hybridization with a 32P-labelled oligomer probe. This technique achieved the type-specific detection of coxsackievirus B3 even at a level of less than one of the 50% tissue culture infective dose (TCID50). With this technique, viral RNA was detected up to the 28th day after inoculation. Thus, the viral RNA persisted in the hearts of these mice even when infectious virus could no longer be detected. PMID- 1312650 TI - Endothelium-derived relaxing factor in human coronary arteries. PMID- 1312651 TI - Thrombomodulin, an endothelial anticoagulant; its structure, function and expression. AB - Thrombomodulin is an endothelium-associated glycoprotein that converts thrombin from a procoagulant protease to an anticoagulant. Thrombin, a key enzyme in thrombus formation, binds to thrombomodulin on the endothelium. However after thrombin binds to thrombomodulin, it fails to act on the coagulation factors and platelets, and its ability to activate protein C is enhanced more than 1,000 fold. This article reviews the recent progress in the study of thrombomodulin. PMID- 1312652 TI - Effects of interleukin-1 (IL-1) on postsurgical macrophage secretion of protease and protease inhibitor activities. AB - Although peritoneal macrophages secrete a variety of inflammatory mediators and proteases during postsurgical repair of the peritoneum, regulation of this secretion is poorly understood. Here, the responsivity of peritoneal macrophages to interleukin-1 (IL-1) stimulation in vitro, measured by the secretion of protease and protease inhibitor activities, was evaluated as a function of postsurgical time. Macrophages were harvested at various times after peritoneal sidewall abrasion, isolated by discontinuous density centrifugation and cultured with varying concentrations of IL-1. IL-1 increased the secretion of plasminogen activator (PA) activity by peritoneal macrophages in a concentration-dependent manner on postsurgical Days 0, 3, 10, and 14. Macrophages harvested on postsurgical Day 1 after surgery responded only to high concentration of IL-1, while on Days 5 and 7 all doses of IL-1 stimulate PA. On Days 7, 10, and 14 after surgery, the secretion of PA activity (after acid treatment) by postsurgical macrophages was generally high and increased with IL-1 treatment. The level of PA activity after inactivation of acid labile inhibitors (PAI) also increased in a dose-dependent manner on Days 0, 3, and 5. Although Day 1 macrophages expressed the highest PAI activity of all groups, they had relatively low responsivity to IL-1 with regards to PAI secretion. The level of elastase activity by postsurgical macrophages was lowest on Day 1, highest on Day 7, and decreased thereafter. All concentrations of IL-1 inhibited elastase activity of macrophages on Day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312653 TI - Prothrombotic and fibrinolytic function of normal and perturbed endothelium. AB - Endothelium mediates thrombosis and fibrinolysis in part through cell-based production and binding of coagulation factors and anticoagulant moieties. A variety of biologically active agents (homocysteine, interleukin-1, and endotoxin) and environmental factors (mechanical injury and hypoxia) can upset the homeostasis of the coagulation system leading in vitro and in vivo to abnormal propensity for thrombin formation. None of the above agents or any similar agents have been demonstrated to inhibit clotting factors or thrombosis formation. As one would expect, injury to endothelium even on a sublethal basis promotes a procoagulant response. This procoagulant response appears to be multifactorial and multiphasic. Gross injury leads to factor release by dead or dying cells with rapid promotion of thrombosis by neighboring infact cells. A more subtle prothrombotic state promulgated by viable cells appears after sublethal perturbation and is characterized by protein synthesis-dependent production of endothelial-produced clotting factors in the early stages of injury with subsequent return to normal levels of these factors by 24 hr. A second phase of abnormal levels of fibrinolysis inhibitors and possible reduction in fibrinolysis promoters appears to follow up to 48 hr after the initial injury. Thus the cell can be viewed as producing means of promoting thrombus formation followed by preventing thrombus dissolution. The data presented in this article are primarily cell culture data and are thus limited both in physiologic applicability and in ability to define over long periods the relevance of those findings to other cells in the hemostatic system. Nonetheless, in vivo data of endothelial perturbation correlate with the in vitro findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312654 TI - Iodine125 interstitial brachytherapy in the treatment of carcinoma of the lung. AB - In a prospective study, 14 patients with primary non-oat cell lung carcinoma were treated with intraoperative Iodine125 (I125) implantation of the lung tumor via lateral thoracotomy or median sternotomy. Staging mediastinal node dissection was performed in each case. Patients were selected when wedge or segmental resections were not technically feasible, such that lobectomy or completion pneumonectomy would have been required or pulmonary function studies were poor. Doses ranged from 8,000 cGy at the periphery to 20,000 cGy at the center. With a minimum 12 month follow-up, mean and median survivals were 16.7 and 15.1 months, respectively. Local control was achieved in 10 of 14 patients (71%) with all local failures occurring in pathologic stage III patients. When separated according to tumor size, local control was obtained in six of seven tumors of less than 3 cm and four of five tumors of 3-5 cm. Both cases with masses greater than 5 cm failed locally. There was one operative mortality and two postoperative complications. All other patients were discharged within one week of surgery. There was no radiation pneumonitis. I125 lung brachytherapy is an excellent alternative treatment for T1 and T2 tumors when medical conditions preclude curative resection. PMID- 1312655 TI - Accuracy of the bronchoscopic DNA content analysis of non-small-cell lung carcinoma. AB - To assess the accuracy of the bronchoscopic DNA content analysis, samples of non small-cell lung carcinomas (NSCLC) were investigated by means of flow cytometry. Samples were dissociated using the detergent Triton X-100. In 58 NSCLC cases, 39 (67%) had DNA aneuploid tumors. We compared the DNA indices of bronchoscopic brushing samples with 21 corresponding surgical samples. In 16 (76%) cases, DNA ploidy of both bronchoscopic and surgical samples were in concordance. In 3 (14%) cases, both bronchoscopic and surgical sample showed DNA aneuploidy, but the number of the DNA aneuploid stem cell lines was different. The cause of these differences was ascribed to the intratumor DNA heterogeneity. In 2 (10%) cases, the bronchoscopic sample showed DNA diploidy, but the surgical sample showed DNA aneuploidy. In these cases, tumor cells obtained by bronchoscopic brushing were so few that the small DNA aneuploid peak was undetectable in the DNA histogram. But the tumor DNA ploidy was evaluated correctly in 90% of 21 cases using bronchoscopic samples. Consequently, despite some drawbacks, the DNA ploidy diagnosis using bronchoscopic samples in this relatively small study, was almost as reliable as surgical samples. PMID- 1312656 TI - Viruses and Hodgkin's disease. PMID- 1312657 TI - A comprehensive model for the treatment of nicotine dependence in a medical setting. AB - We have summarized the basic components of a comprehensive model for the treatment of nicotine addiction in a medical setting. It is a labor-intensive program with emphasis on individual assessment and the development of individual treatment programs adaptable to all levels of nicotine dependence. We anticipate that this model will be increasingly used by medical centers in the future. As more traditional programs successfully treat the less severely nicotine-dependent patients, more severely dependent smokers are left in need of more intensive services. We have already begun to see this trend in our practice, requiring more counselor time for individual follow-up and referral into our group therapy programs. Adjunctive pharmacologic therapy is an exciting and promising area, but best results include associated behavioral intervention. Reimbursement remains a major impediment to patient involvement in many of these programs. This impediment will be overcome when third-party payers begin to cover these services as endorsed by the Surgeon General and the United States Department of Health and Human Services. PMID- 1312658 TI - Effects of GABA receptor stimulation on the release of [3H]GABA from slices of rat neostriatum. AB - Slices of rat neostriatum were incubated in Krebs-Henseleit medium. Modulation of [3H]GABA release by GABA agonists and antagonists was investigated. The GABAA receptor agonists muscimol (0.1 microM) and isoguvacine (5 microM) enhanced the stimulated release of [3H]GABA. The antagonists picrotoxin (1 microM) and bicuculline (50 microM) prevented the effects of the agonists. In the presence of naloxone (1 microM), which blocked the effects of enkephalinergic neurons within the slice preparation, muscimol (1 microM) no longer affected the release of [3H]GABA. PMID- 1312659 TI - Relapsing hepatitis A. Review of 14 cases and literature survey. AB - We have reviewed our experience with 14 cases of relapsing hepatitis A (RH-A), as well as 68 cases reported in the literature. Relapse occurs in 3 to 20% of patients with acute hepatitis A, and rarely takes the form of a polyphasic disease (multiple relapses). After a stage of typical hepatitis A, remission phase ensues, with partial or complete resolution of clinical and biochemical manifestations. Relapse usually occurs after a short period (usually less than 3 weeks). Relapse is usually clinically milder than the first phase, with variable liver function abnormalities and a tendency toward more marked cholestatic features. Not uncommonly, immune manifestations occur during this phase, including purpura, nephritis, and arthralgia, with common laboratory findings of rheumatoid factor as well as false-positive reaction to HCV-EIA tests. The clinical course in relapsing hepatitis A is almost always benign, and uneventful recovery is the rule with few exceptions. Steroid treatment, first reported in the present series, resulted in marked clinical improvement. Preliminary results suggest that R-HA is associated with a continuing viremia as well as shedding of virus in stools during the relapse phase. The pathogenesis of R-HA probably involves an interaction between persistent viral infection and immune mechanisms responding to the continuing antigenic stimulation. PMID- 1312661 TI - High-risk human papillomavirus types in cytologically normal cervical scrapes from Kenya. AB - Seventy-seven women with normal cervical cytology on routine visit to a family planning clinic in Nairobi, Kenya, were analysed for genital human papillomavirus (HPV) types by polymerase chain reaction (PCR). We applied a general primer pair (GP60/GP124) recognising sequences conserved among HPV types 6, 11, 16, 18, 31 and 33. Of the 77 specimens tested 15 (19.5%) proved to be positive for genital HPV. Amplification products were examined for the presence of high-risk HPV types by Slot-blot hybridization. Out of the 15 PCR-positive samples, 4 were positive for HPV 16.3 for HPV 18, while 1 contained both HPV 16 and 33. HPV DNA prevalence in this group of women from a "high-risk" area is similar to that in "low-risk" Swedish women but much lower than in cervical cancer samples from the same region. PMID- 1312660 TI - Early appearance and biphasic kinetics of IgG antibody against hepatitis C virus protein C100-3. AB - Antibody to recombinant hepatitis C virus (HCV) protein C100 (anti-C100) was measured for a period of 6 months by enzyme immunoassay in nine prospectively followed non A-nonB (NANBH) cases which occurred after cardiac surgery at a hospital in Rio de Janeiro (Brazil). At least seven cases were infected with HCV; four of these developed chronic hepatitis as shown in liver biopsy at the 6th month after transfusion. The first elevation of alanine aminotransferase (ALT) occurred between 15 and 45 days after transfusion and ALT values remained elevated for 45 days in resolving hepatitis, whereas in chronic cases fluctuation levels were observed until the end of the study. Anti-C100 appeared after 15 to 30 days, decreased after some weeks, and rose finally to high concentrations except in one resolving case where it disappeared. We conclude that both in acute and chronic hepatitis C an early antibody response occurs which may, however, be undetectable in some cases. After several months all chronic and some resolving cases develop a second stronger response. PMID- 1312662 TI - [Changes of the insulin and glucagon receptors in bile-duct ligated rats]. AB - The specific bindings of insulin and glucagon to 40000g pellets including hepatic plasma membrane were measured at 1, 2 or 4 weeks after bile-duct ligation or sham operation in rats. At 1 week after operation, insulin bindings were similar in both bile-duct ligated and control rats, however, glucagon binding in bile-duct ligated rats (30.1 +/- 5.99%) was significantly (p less than 0.01) lower than that in control rats (42.8 +/- 8.13%). At 2 and 4 weeks after operation, insulin bindings in bile-duct ligated rats (2 weeks: 35.2 +/- 3.32%, 4 weeks: 32.3 +/- 4.62%) were significantly (p less than 0.05) lower than those in control rats (2 weeks: 39.7 +/- 5.12%, 4 weeks: 38.4 +/- 3.85%). Therefore, glucagon bindings in bile-duct ligated rats (2 weeks: 26.3 +/- 4.32%, 4 weeks: 26.9 +/- 4.06%) were significantly (p less than 0.01) lower than those in control rats (2 weeks: 42.0 +/- 3.95%, 4 weeks: 45.3 +/- 4.29%). Decrease of insulin bindings, however, was less than that of glucagon bindings. Changes of the insulin and glucagon receptors on the hepatic plasma membrane suggested a reason for a disturbance of carbohydrate metabolism in the liver cell with obstructive jaundice. PMID- 1312663 TI - The C-terminal SH2 domain of p85 accounts for the high affinity and specificity of the binding of phosphatidylinositol 3-kinase to phosphorylated platelet derived growth factor beta receptor. AB - Upon stimulation by its ligand, the platelet-derived growth factor (PDGF) receptor associates with the 85-kDa subunit of phosphatidylinositol (PI) 3 kinase. The 85-kDa protein (p85) contains two Src homology 2 (SH2) domains and one SH3 domain. To define the part of p85 that interacts with the PDGF receptor, a series of truncated p85 mutants was analyzed for association with immobilized PDGF receptor in vitro. We found that a fragment of p85 that contains a single Src homology domain, the C-terminal SH2 domain (SH2-C), was sufficient for directing the high-affinity interaction with the receptor. Half-maximal binding of SH2-C to the receptor was observed at an SH2-C concentration of 0.06 nM. SH2 C, like full-length p85, was able to distinguish between wild-type PDGF receptor and a mutant receptor lacking the PI 3-kinase binding site. An excess of SH2-C blocked binding of full-length p85 and PI 3-kinase to the receptor but did not interfere with the binding of two other SH2-containing proteins, phospholipase C gamma and GTPase-activating protein. These results demonstrate that a region of p85 containing a single SH2 domain accounts both for the high affinity and specificity of binding of PI 3-kinase to the PDGF receptor. PMID- 1312664 TI - Transcription of germ line V alpha segments correlates with ongoing T-cell receptor alpha-chain rearrangement. AB - M14T is a virally transformed immature T-cell line which continues to rearrange its T-cell antigen receptor (TCR) alpha-chain genes in vitro and thus represents a dynamic system for studying TCR assembly. In an effort to investigate whether the TCR alpha locus is accessible for V(D)J rearrangement events, we examined M14T cells for the presence of germ line TCR alpha transcripts. Several unrearranged V alpha segments were found to be transcriptionally active in M14T cells. By comparison, germ line V alpha transcripts are absent in nonlymphoid and pro-T-cell lines and barely detectable in mature T-cell lines, suggesting that this phenomenon is likely stage and tissue specific. We demonstrate a perfect correlation between transcriptionally active V alpha segments and their involvement in ongoing V alpha-to-J alpha rearrangements. In addition, data suggesting that the unrearranged J alpha locus is also transcriptionally active in the M14T line are presented. Furthermore, the recombination-activating genes RAG-1 and RAG-2 are differentially expressed, with RAG-2 detectable only by polymerase chain reaction, implying that very low levels of one of these gene products are sufficient to complement the other to facilitate VJ rearrangements. These findings provide the first direct evidence for an accessibility model of antigen receptor rearrangement in T cells. PMID- 1312665 TI - In vitro transfection of fresh thymocytes and T cells shows subset-specific expression of viral promoters. AB - We describe conditions under which exogenous DNA templates can be introduced for transient expression into primary murine T lymphocytes. T cells at various stages of development, including concanavalin A-activated splenic T cells, immature pre T cells, and even small cortical thymocytes, could be successfully transfected. A variety of model DNA constructs were compared in which different viral promoter regions were used to drive expression of the chloramphenicol acetyltransferase (CAT) reporter gene. All showed enhanced expression in cells that had been acutely stimulated with the Ca2+ ionophore A23187 and phorbol ester as chemical proxies for T-cell receptor-mediated signals. In addition, splenocytes but not thymocytes required prior treatment with a mitogen and interleukin-2 in order to express these constructs, implying that even postmitotic thymocytes may be held in a quasiactivated state. A most striking result was the finding that the viral regulatory sequences in the Rous sarcoma virus long terminal repeat and the simian virus 40 early region were subject to sharply differential regulation, with a rank order that changed depending on the developmental stage of the T cells. The most immature thymic blasts and several lymphoma cell lines expressed the pRSV-Cat and pSV2-Cat constructs similarly, but cortical thymocytes exhibited a strong preference for pSV2-Cat. Splenic concanavalin A-stimulated blasts, on the other hand, slightly preferred pRSV-Cat, a tendency which became exaggerated in factor-dependent T-cell lines. The ratio of pRSV-Cat to pSV2-Cat expression varied according to cell type by as much as 500-fold. These results argue against a trivial linkage of promoter preference to cell cycle status but instead provide evidence that activation of T cells at distinct stages of differentiation results in the expression of different ensembles of nuclear regulatory proteins. In contrast to the simian virus 40 and Rous sarcoma virus promoter regions, the long terminal repeats of the retroviruses mink cell focus-forming virus and Akv were expressed well in all primary T-lineage cells. Thus, they represent excellent model promoters for engineering developmental stage-independent expression of exogenous genes in murine T cells. PMID- 1312666 TI - In vitro initiation of transcription by RNA polymerase II on in vivo-assembled chromatin templates. AB - We have studied the initiation of transcription in vitro by RNA polymerase II on simian virus 40 (SV40) minichromosomal templates isolated from infected cells. The efficiency and pattern of transcription from the chromatin templates were compared with those from viral DNA templates by using two in vitro transcription systems, either HeLa whole-cell extract or basal transcription factors, RNA polymerase II, and one of two SV40 promoter-binding transcription factors, LSF and Sp1. Dramatic increases in numbers of transcripts upon addition of transcription extract and different patterns of usage of the multiple SV40 initiation sites upon addition of Sp1 versus LSF strongly suggested that transcripts were being initiated from the minichromosomal templates in vitro. That the majority of transcripts from the minichromosomes were due to initiation de novo was demonstrated by the efficient transcription observed in the presence of alpha-amanitin, which inhibited minichromosome-associated RNA polymerase II, and an alpha-amanitin-resistant RNA polymerase II, which initiated transcription in vitro. The pattern of transcription from the SV40 late and early promoters on the minichromosomal templates was similar to the in vivo pattern of transcription during the late stages of viral infection and was distinct from the pattern of transcription generated from viral DNA in vitro. In particular, the late promoter of the minichromosomal templates was transcribed with high efficiency, similar to viral DNA templates, while the early-early promoter of the minichromosomal templates was inhibited 10- to 15-fold. Finally, the number of minichromosomes competent to initiate transcription in vitro exceeded the amount actively being transcribed in vivo. PMID- 1312667 TI - A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains. AB - Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium. PMID- 1312668 TI - Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. AB - Apolipoprotein CIII (apoCIII), a lipid-binding protein involved in the transport of triglycerides and cholesterol in the plasma, is synthesized primarily in the liver and the intestine. A cis-acting regulatory element, C3P, located at -90 to 66 upstream from the apoCIII gene transcriptional start site (+1), is necessary for maximal expression of the apoCIII gene in human hepatoma (HepG2) and intestinal carcinoma (Caco2) cells. This report shows that three members of the steroid receptor superfamily of transcription factors, hepatocyte nuclear factor 4 (HNF-4), apolipoprotein AI regulatory protein 1 (ARP-1), and Ear3/COUP-TF, act at the C3P site. HNF-4 activates apoCIII gene expression in HepG2 and Caco2 cells, while ARP-1 and Ear3/COUP-TF repress its expression in the same cells. HNF 4 activation is abolished by increasing amounts of ARP-1 or Ear3/COUP-TF, and repression by ARP-1 or Ear3/COUP-TF is alleviated by increasing amounts of HNF-4. HNF-4 and ARP-1 bind with similar affinities to the C3P site, suggesting that their opposing transcriptional effects may be mediated by direct competition for DNA binding. HNF-4 and ARP-1 mRNAs are present within the same cells in the liver and intestine, and protein extracts from hepatic tissue, HepG2, and Caco2 cells contain significantly more HNF-4 than ARP-1 or Ear3/COUP-TF binding activities. These findings suggest that the transcription of the apoCIII gene in vivo is dependent, at least in part, upon the intracellular balance of these positive and negative regulatory factors. PMID- 1312669 TI - Complex intrachromosomal rearrangement in the process of amplification of the L myc gene in small-cell lung cancer. AB - The L-myc gene was first isolated from a human small-cell lung cancer (SCLC) cell line on the basis of its amplification and sequence similarity to c-myc and N myc. A new mechanism of L-myc activation which results from the production of rlf L-myc fusion protein was recently reported. On the basis of our earlier observation of a rearrangement involving amplified L-myc in an SCLC cell line, ACC-LC-49, we decided to investigate this rearrangement in detail along with the structure of L-myc amplification units in five additional SCLC cell lines. We report here the identification of a novel genomic region, termed jal, which is distinct from rlf and is juxtaposed to and amplified with L-myc during the process of DNA amplification of the region encompassing L-myc. Long-range analysis using pulsed-field gel electrophoresis revealed that the amplified L-myc locus is involved in highly complex intrachromosomal rearrangements with jal and/or rlf. Our results also suggest that the simultaneous presence of rearrangements both in rlf intron 1 and in regions immediately upstream of L-myc may be necessary for the expression of rlf-L-myc chimeric transcripts. PMID- 1312670 TI - Hematologic disease induced in BALB/c mice by a bcr-abl retrovirus is influenced by the infection conditions. AB - Irradiated mice reconstituted with bone marrow cells infected with a retrovirus carrying the bcr-abl oncogene of human chronic myeloid leukemia are subject to a range of neoplastic hematopoietic diseases, both myeloid and lymphoid. Comparison of DBA/2 and C57BL/6 mice has revealed a marked strain difference in susceptibility to the various tumor types. The present study, performed with BALB/c mice, indicates that the kinetics and nature of the induced disease can be modulated by the infection procedure, as well as the genetic background, and that retroviral regulatory sequences may influence the outcome. A distinctive clonal myeloproliferative disorder, somewhat akin to chronic myeloid leukemia but with prominent erythroid and mast cell components, as well as granulocytic excess, was characterized. PMID- 1312671 TI - The gene for erythropoietin receptor is expressed in multipotential hematopoietic and embryonal stem cells: evidence for differentiation stage-specific regulation. AB - The principal regulator of erythropoiesis is the glycoprotein erythropoietin, which interacts with a specific cell surface receptor (EpoR). A study aimed at analyzing EpoR gene regulation has shown that both pluripotent embryonal stem cells and early multipotent hematopoietic cells express EpoR transcripts. Commitment to nonerythroid lineages (e.g., macrophage or lymphocytic) results in the shutdown of EpoR gene expression, whereas commitment to the erythroid lineage is concurrent with or followed by dramatic increases in EpoR transcription. To determine whether gene activity could be correlated with chromatin alterations, DNase-hypersensitive sites (HSS) were mapped. Two major HSS located in the promoter region and within the first intron of the EpoR gene are present in all embryonal stem and hematopoietic cells tested, the intensities of which correlate well with EpoR expression levels. In addition, a third major HSS also located within the first intron of the EpoR gene is uniquely present in erythroid cells that express high levels of EpoR. Transfection assays show that sequences surrounding this major HSS impart erythroid cell-specific enhancer activity to a heterologous promoter and that this activity is at least in part mediated by GATA 1. These data, together with concordant expression levels of GATA-1 and EpoR in both early multipotent hematopoietic and committed erythroid cells, support a regulatory role of the erythroid cell-specific transcription factor GATA-1 in EpoR transcription in these cells. However, the lack of significant levels of GATA-1 expression in embryonal stem cells implies an alternative regulatory mechanism of EpoR transcription in cells not committed to the hematopoietic lineage. PMID- 1312674 TI - Single fiber EMG reference values: a collaborative effort. Ad Hoc Committee of the AAEM Special Interest Group on Single Fiber EMG. AB - Single fiber electromyography (SFEMG) measurements of fiber density and jitter are used in the diagnosis of a variety of peripheral nervous system disorders. However, the normal values of these measurements for most muscles and age groups are not well documented in the literature. We present a retrospective and prospective multicenter collection of SFEMG jitter and fiber density data from control subjects obtained for the purpose of defining reference values for many muscles and different ages. The data and calculated upper limits for fiber density, individual pair jitter, and mean jitter are presented for each muscle in tabular and graphical format, for different age groups. PMID- 1312673 TI - A presumptive helicase (MOT1 gene product) affects gene expression and is required for viability in the yeast Saccharomyces cerevisiae. AB - Exposure of a haploid yeast cell to mating pheromone induces transcription of a set of genes. Induction is mediated through a cis-acting DNA sequence found upstream of all pheromone-responsive genes. Although the STE12 gene product binds specifically to this sequence element and is required for maximum levels of both basal and induced transcription, not all pheromone-responsive genes are regulated in an identical manner. To investigate whether additional factors may play a role in transcription of these genes, a genetic screen was used to identify mutants able to express pheromone-responsive genes constitutively in the absence of Ste12. In this way, we identified a recessive, single gene mutation (mot1, for modifier of transcription) which increases the basal level of expression of several, but not all, pheromone-responsive genes. The mot1-1 allele also relaxes the requirement for at least one other class of upstream activating sequence and enhances the expression of another gene not previously thought to be involved in the mating pathway. Cells carrying mot1-1 grow slowly at 30 degrees C and are inviable at 38 degrees C. The MOT1 gene was cloned by complementation of this temperature-sensitive lethality. Construction of a null allele confirmed that MOT1 is an essential gene. MOT1 residues on chromosome XVI and encodes a large protein of 1,867 amino acids which contains all seven of the conserved domains found in known and putative helicases. The product of MOT1 is strikingly homologous to the Saccharomyces cerevisiae SNF2/SW12 and RAD54 gene products over the entire helicase region. PMID- 1312672 TI - Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation. AB - Transcriptional activation of the murine Cyp1a-1 (cytochrome P(1)450) gene by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (dioxin) requires the aromatic hydrocarbon (Ah) receptor and the interaction of an inducer-receptor complex with one or more of the Ah-responsive elements (AhREs) located about 1 kb upstream from the transcriptional initiation site. We find that treatment of mouse hepatoma Hepa-1 cells with 2-aminopurine, an inhibitor of protein kinase activity, inhibits CYP1A1 mRNA induction by TCDD as well as the concomitant increase in CYP1A1 enzyme activity. Formation of DNA-protein complexes between the Ah receptor and its AhRE target is also inhibited by 2-aminopurine, as determined by gel mobility shift assays. Phosphorylation is required for the formation of Ah receptor-specific complexes, since in vitro dephosphorylation of nuclear extracts from TCDD-treated Hepa-1 cells abolishes the capacity of the Ah receptor to form specific complexes with its cognate AhRE sequences. To determine whether any one of several known protein kinases was involved in the transcriptional regulation of the Cyp1a-1 gene, we treated Hepa-1 cells with nine other protein kinase inhibitors prior to induction with TCDD; nuclear extracts from these cells were analyzed for their capacity to form specific DNA-protein complexes. Only extracts from cells treated with staurosporine, a protein kinase C inhibitor, were unable to form these complexes. In addition, staurosporine completely inhibited CYP1A1 mRNA induction by TCDD. Depletion of protein kinase C by prolonged treatment with phorbol ester led to the complete suppression of CYP1A1 mRNA induction by TCDD. We conclude that (i) phosphorylation is necessary for the formation of a transcriptional complex and for transcriptional activation of the Cyp1a-1 gene; (ii) the phosphorylation site(s) exists on at least one of the proteins constituting the transcriptional complex, possibly the Ah receptor itself; and (iii) the enzyme responsible for the phosphorylation is likely to be protein kinase C. PMID- 1312675 TI - Ca(2+)-ATPase and Na(+)-K(+)-ATPase content in skeletal muscle from malignant hyperthermia patients. AB - The purpose of this study was to determine the concentration of Ca(2+)-ATPase and Na(+)-K(+)-ATPase in biopsies from vastus lateralis muscle of 24 patients, who underwent a diagnostic contracture test for susceptibility to malignant hyperthermia (MH). Ca(2+)-ATPase was quantified as the Ca(2+)-dependent 32P incorporation in whole muscle homogenates. Na(+)-K(+)-ATPase was quantified as the [3H]ouabain-binding capacity in intact muscle samples. These methods avoid isolation of membranes, a procedure that may influence the results due to interindividual variation in recovery. The results show that both enzymes can be determined in (frozen) muscle biopsies weighing 50 mg. Neither the concentration of Ca(2+)-ATPase nor that of Na(+)-K(+)-ATPase differed in biopsies from subjects diagnosed as susceptible (MHS) or nonsusceptible (MHN) to MH. Our data support the view that changes in the concentration of Ca(2+)-ATPase and/or Na(+)-K(+) ATPase do not play a primary role in the pathogenesis of MH. PMID- 1312676 TI - Segmental cytochrome c-oxidase deficiency in CPEO: teased muscle fiber analysis. AB - In an attempt to elucidate the pathogenesis of focal cytochrome c-oxidase (COX) deficiency in skeletal muscle from patients with chronic progressive external ophthalmoplegia (CPEO), we examined the longitudinal distribution of COX activity in single muscle fibers from 6 CPEO patients with muscle mitochondrial DNA (mtDNA) deletions. A new method for teasing single muscle fibers, recently developed in our laboratory, revealed fibers with COX-positive and -negative segments in all 6 patients. The borders between the enzyme-positive and -negative segments in these fibers were sharply delineated, so that the length of each COX negative segments could be accurately measured. The proportion of the sum of the lengths of the enzyme-negative segments to the total length of the muscle fibers correlated well with the proportion of deleted mtDNA, suggesting that abnormal mitochondria harboring mutant mtDNA may be responsible for the focal loss of COX activity. PMID- 1312677 TI - Plasmapheresis in chronic demyelinating polyneuropathy. PMID- 1312678 TI - Plasmapheresis in chronic demyelinating polyneuropathy. PMID- 1312679 TI - Oxygen activation and the conservation of energy in cell respiration. AB - Many of the membrane-associated oxidases that catalyse respiratory reduction of O2 to water simultaneously couple this exergonic reaction to the translocation of protons across the inner mitochondrial membrane, or the cell membrane in prokaryotes, a process by which metabolic energy is conserved for subsequent synthesis of ATP. The molecular mechanism of O2 reduction and its linkage to H+ translocation are now emerging. The bimetallic haem iron-copper reaction centre in this family of enzymes is the critical structure for catalysis of both these processes. PMID- 1312680 TI - Clustering of voltage-dependent sodium channels on axons depends on Schwann cell contact. AB - In myelinated nerves, segregation of voltage-dependent sodium channels to nodes of Ranvier is crucial for saltatory conduction along axons. As sodium channels associate and colocalize with ankyrin at nodes of Ranvier, one possibility is that sodium channels are recruited and immobilized at axonal sites which are specified by the subaxolemmal cytoskeleton, independent of glial cell contact. Alternatively, segregation of channels at distinct sites along the axon may depend on glial cell contact. To resolve this question, we have examined the distribution of sodium channels, ankyrin and spectrin in myelination-competent cocultures of sensory neurons and Schwann cells by immunofluorescence, using sodium channel-, ankyrin- and spectrin-specific antibodies. In the absence of Schwann cells, sodium channels, ankyrin and spectrin are homogeneously distributed on sensory axons. When Schwann cells are introduced into these cultures, the distribution of sodium channels dramatically changes so that channel clusters on axons are abundant, but ankyrin and spectrin remain homogeneously distributed. Addition of latex beads or Schwann cell membranes does not induce channel clustering. Our results suggest that segregation of sodium channels on axons is highly dependent on interactions with active Schwann cells and that continuing axon-glial interactions are necessary to organize and maintain channel distribution during differentiation of myelinated axons. PMID- 1312681 TI - Epstein-Barr virus infection and replication in a human epithelial cell system. AB - Epstein-Barr virus, a human herpesvirus with oncogenic potential, infects two target tissues in vivo: B lymphocytes, where the infection is largely non productive, and stratified squamous epithelium in which virus replication occurs. The interaction with B cells, initiated through virus binding to the B-cell surface molecule CR2 (ref. 4), has been studied in vitro and the virus 'latent' genes associated with B-cell growth transformation defined. By comparison, viral infection of epithelium remains poorly understood, reflecting the lack of an appropriate cell-culture model. Here we describe the development of such a model using as targets CR2-expressing transfected cells of two independent human epithelial lines. A high proportion of these cells bind virus and become actively infected, expressing the small EBER RNAs (small non-polyadenylated virus-coded RNAs) and the Epstein-Barr nuclear antigen 1 but not other latent proteins; thereafter, under conditions favouring epithelial differentiation, up to 30% of the cells can be induced to enter virus productive cycle with some progressing to full virus replication. We find significant differences between laboratory virus strains in their ability to infect epithelium that do not correlate with their B cell growth-transforming activity. PMID- 1312682 TI - Quantal calcium release by purified reconstituted inositol 1,4,5-trisphosphate receptors. AB - Release of intracellular Ca2+ by inositol 1,4,5-trisphosphate (InsP3) occurs through specific receptor proteins which are ligand-activated Ca2+ channels. Changes in intracellular Ca2+ regulate many cellular functions. This Ca2+ release is a discontinuous quantal process in which successive increments of InsP3 transiently release precise amounts of Ca2+ (refs 4-6). Possible explanations of quantal Ca2+ release have included rapid degradation of InsP3, reciprocity of Ca2+ release and sequestration, desensitization of InsP3 receptors, or actions of InsP3 on discrete compartments of Ca2+ with variable sensitivity to InsP3 (ref. 4). We successfully reconstituted InsP3-induced Ca2+ flux in vesicles containing only purified InsP3 receptor protein. The reconstituted vesicles retain the regulatory features of the InsP3 receptor, including phosphorylation sites and modulation of Ca2+ release by adenine nucleotides. Using these reconstituted vesicles, we show here that quantal flux of Ca2+ elicited by InsP3 is a fundamental property of its receptor. PMID- 1312683 TI - Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. AB - We retrospectively evaluated the effect of plasmapheresis (PE) in seven patients with paraneoplastic encephalomyelitis (PEM), small-cell lung carcinoma, and anti Hu antibodies, and four patients with paraneoplastic cerebellar degeneration (PCD), ovarian or breast cancer, and anti-Yo antibodies. In addition to PE, patients received prednisone (nine), cyclophosphamide (eight), or treatment of the tumor (five). All but one patient were severely disabled by the time PE began. The clinical outcome was compared with that of five patients (PEM, four; PCD, one) who only had treatment of the tumor. Only one of these five patients had a severe neurologic deficit at the onset of the antineoplastic treatment. No patient improved. Two patients treated with PE and antineoplastic therapy and three who only received treatment of the tumor remained stable for at least 6 months. Four of the five patients with a stable course started the treatment when the neurologic deficit was not severe. We conclude that the efficacy of PE with other immunosuppressive therapies in the stabilization of the neurologic deficit is uncertain. PMID- 1312684 TI - Thermography. PMID- 1312685 TI - Thermography. PMID- 1312686 TI - Thermography. PMID- 1312687 TI - Thermography. PMID- 1312688 TI - Bicarbonate administration in acidaemia--is it therapeutic? PMID- 1312689 TI - Significance of oral hairy leukoplakia. AB - Since the original description of oral hairy leukoplakia among homosexual men in San Francisco in 1984, this white lesion of the tongue has been seen in the mouths of persons infected with the human immunodeficiency virus (HIV) worldwide. Its presence in HIV-positive persons usually but not always indicates fairly rapid progression to acquired immunodeficiency syndrome in the absence of antiretroviral therapy. Although the lesion appears to be common in HIV-positive persons, it is also, albeit rarely, seen in other conditions associated with immunosuppression. Epstein-Barr virus is associated with and presumably causes hairy leukoplakia, and the lesion offers insights into the biology of this ubiquitous DNA-oncogenic virus. PMID- 1312690 TI - Viral infections of the head and neck among HIV-seropositive patients. AB - Many viruses cause opportunistic infections in HIV-positive patients. Those that cause oral lesions include herpes simplex, varicella zoster, Epstein-Barr virus, cytomegalovirus, and papillomavirus. Importantly, many of the herpes-group viruses are able to augment immunosuppression and some actually transactivate HIV replication-inducing genetic sequences. This article reviews the role of viral agents in the activation of HIV replication and details the features of the reported oral lesions that represent viral opportunistic infections. PMID- 1312691 TI - Oral manifestations of HIV infection in children. AB - Human immunodeficiency virus (HIV) infection was first recognized in children in 1983 and has now assumed the proportions of a major public health challenge. This article briefly reviews, on the basis of the literature, the epidemiology, diagnosis, clinical and immunologic characteristics, and prognosis of HIV infection in children. The clinical oral manifestations in children are described on the basis of the literature and the personal observations of HIV-infected pediatric patients. PMID- 1312692 TI - Management of oral health in persons with HIV infection. AB - Prevention and treatment of oral disease is required to maintain quality of life and to improve prognosis of patients infected with the human immunodeficiency virus (HIV). Management requires a team approach, and close collaboration with the appropriate responsible physicians and other health care workers is necessary. Oral infection is frequent and usually opportunistic, and management is based on certain principles. Infections may disseminate and can be persistent and severe; multiple concurrent or consecutive infections with different microorganisms are frequent; fungal, viral, and parasitic infections are rarely curable; and long-term antimicrobial therapy may be required. This article reviews the management of oral candidiasis, hairy leukoplakia, and infections with herpes simplex virus, varicella-zoster virus, and cytomegalovirus. The management of Kaposi's sarcoma, lymphomas, aphthous ulceration, gangrenous stomatitis, bleeding, xerostomia, and adverse drug reactions is also described. Treatment should avoid further immunosuppression and inducement of xerostomia or caries, and should be designed to avoid adverse drug reactions and possible drug interactions. PMID- 1312693 TI - Induction of Xenopus oocyte meiotic maturation by the dbl oncogene product. AB - The dbl oncogene was originally identified by transfection of NIH3T3 cells with DNA from a human diffuse B-cell lymphoma. The dbl oncogene product is a cytoplasmic phosphoprotein distributed between the cytosolic and cytoskeletal matrix-associated membrane fractions. Nucleotide sequence analysis has indicated that the predicted dbl product is very hydrophilic with no detectable similarity to known oncogene products. We have more recently discovered that a region of dbl essential for its transforming activity shows significant sequence similarity to a yeast cell cycle gene, CDC24, which is involved in cell polarity and bud formation in the division cycle of Saccharomyces cerevisiae. This sequence similarity suggests a possible role for dbl in cell division. We report here that the dbl oncogene product is able to induce maturation of Xenopus oocytes. Germinal vesicle breakdown (GVBD) was observed when oocytes were microinjected with the soluble fraction of SF9 insect cells infected with a dbl recombinant baculovirus as well as with the in vitro-transcribed dbl mRNA. Moreover, extracts of oocytes microinjected with dbl mRNA showed activation of H1 histone kinase activity. These findings define a new biologic activity of the dbl product and provide the opportunity to analyse dbl interactions with other components of signaling pathways involved in oocyte maturation. PMID- 1312694 TI - Early gene expression in lymphoma-associated hamster polyomavirus viral genomes. AB - Hamster polyomavirus (HaPV) is the causal agent of hair follicle epithelioma in hamsters belonging to a colony bred in Berlin-Buch. These tumors shed virus particles that are assembled in the keratinized layer of the epidermis. By contrast, HaPV induces lymphomas after inoculation into newborn hamsters from a distinct colony bred in Potsdam. These lymphoid tumors accumulate massive amounts of episomal viral genomes characterized by deletions that alter specifically the regulatory and the late coding sequences. Assuming that these alterations of the regulatory region may affect the transcription of the viral oncogenes in the tumor cells, the transcriptional activity of the wild-type and deleted early promoters have been studied in vitro in transient chloramphenicol acetyltransferase (CAT) expression assays. These assays performed in various cell types demonstrate that both versions of the HaPV early promoter carry a weak constitutive activity. Simultaneous expression of the HaPV early gene products leads to a strong stimulation of CAT activity with a concomitant activation of the replication of the plasmid constructs. The results obtained with origin defective CAT vectors indicate that the replication contributes significantly to the stimulating effect of the early gene products. Indeed, transfection of massive amounts of CAT vectors that are unable to replicate can simulate the dosage effect of replication and also leads to measurable CAT activities. Under these conditions, the wild-type promoter is more active than the deleted version, indicating that sequences within the deletion carry a distinct stimulatory effect on transcription. This conclusion is supported by the observation that the lymphoma cells contain a low level of early transcripts, indicating that the deleted episomal viral templates accumulated in these tumors carry a weak transcriptional activity. PMID- 1312695 TI - Molecular rearrangements of the MYL gene in acute promyelocytic leukemia (APL, M3) define a breakpoint cluster region as well as some molecular variants. AB - Genomic DNA probes generated from the retinoic acid receptor alpha (RARA) gene located on chromosome 17 and from the MYL gene located on chromosome 15 were used to study the chromosome 15 breakpoints resulting from the t(15; 17) translocation in 26 patients with acute promyelocytic leukemia (APL). In 20 out of 22 patients with a detectable MYL rearrangement, the breakpoints were clustered within a 4.4 kb segment designated MYLbcr. The two remaining patients exhibited a more 5' rearrangement at about 10 kb upstream of the MYLbcr region, implying the lack of at least one MYL gene exon in the resulting MYL-RARA fusion gene. The variation of chromosome breakpoints within the MYL gene may explain size heterogeneity previously observed in some MYL-RARA fusion transcripts expressed in APL cells. PMID- 1312696 TI - High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. AB - We analysed the p53 open reading frame (ORF) in 16 small-cell lung cancer (SCLC) cell lines by direct sequencing of cDNA/PCR products and in 20 SCLC tumors by chemical cleavage and single-strand conformation polymorphism analyses of genomic DNA/PCR products. Abnormalities of p53 were found in 16/16 cell lines (100%) and in 16/20 tumors (80%). In the SCLC cell lines, mutations (59% missense, 18% nonsense and 23% splicing) changing the coding sequence were dispersed between amino acids 68 and 342. In the tumor samples, while the mutations occurred predominantly in exons 5-8, other mutations were located outside these regions. G to T transversions were common, occurring in 32% of the cases. We found no p53 mutations in the corresponding normal tissue from 19 patients whose tumors had p53 lesions, indicating that the mutations were all somatically acquired. In analysing the clinical data of the patients we found no correlation between tumor response to therapy or survival and the location or type of mutations. We conclude from these data that: (1) p53 mutations are found in SCLC with high frequency; (2) p53 mutations in a significant fraction of cases generate cDNAs with nonsense or splicing mutations; and (3) to date, these mutations have all been somatically acquired events. PMID- 1312697 TI - Activation of protein kinase C increases phosphorylation of the L-myc trans activator domain at a GSK-3 target site. AB - The L-myc protein migrates as three distinct differentially phosphorylated bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This phosphorylation can be rapidly increased either by treatment with the protein kinase C (PKC) activator phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or by inhibition of serine/threonine protein phosphatases with okadaic acid. In vitro mutagenesis and phosphoamino acid analyses define the N-terminal serine residues 38 and 42 of L-myc as critical targets for the PKC-dependent phosphorylation. These are the exclusive sites of phosphorylation in the N terminal third of the L-myc protein, and can be phosphorylated in vitro by glycogen synthase kinase 3 beta (GSK-3 beta). A mutant L-myc protein in which these serines have been replaced by alanine residues does not show heterogeneous electrophoretic migration or hyperphosphorylation in response to PKC activation, and is not a substrate for GSK-3 beta in vitro. Similar potential phosphorylation sites are present in c-myc and N-myc in a highly conserved region thought to represent a transcriptional activation domain. We suggest that N-terminal phosphorylation of the L-myc protein is a means of rapid regulation of this oncoprotein, possibly mediated in vivo by the action of GSK-3. PMID- 1312698 TI - K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors. AB - K252a, an efficient serine/threonine protein kinase inhibitor (IC50s of 10 to 30 nM), has been shown to block the neuronal differentiation of rat pheochromocytoma PC12 cells induced by nerve growth factor (NGF). In this report, we demonstrate that K252a is a potent inhibitor (IC50 of 3 nM) of the tyrosine protein kinase activity of the NGF receptor gp140trk, the product of the trk protooncogene. K252a also inhibits the kinase activity of its transforming alleles, the trk oncogenes, and of the related neurotrophin receptors gp145trkB and gp145trkC, the products of the other known members of the trk gene family, trkB and trkC. In contrast, K252a has no effect (even at micromolar concentrations) on other tyrosine protein kinases such as the receptors for EGF and PDGF and the products of the v-src and v-fms oncogenes. In addition, K252a rapidly reverts the transformed phenotype of NIH3T3 cells transformed by either autocrine stimulation of the trk family of receptors by their cognate ligands or by expression of trk oncogenes isolated from human tumors. The selectivity of K252a for the catalytic activity of the trk family of kinases should help to establish the structural basis for the rational design of highly specific tyrosine protein kinase inhibitors. PMID- 1312699 TI - Rearrangement and co-amplification of L-myc and rlf in primary lung cancer. AB - We have recently characterized a gene fusion and chimeric protein product formed by L-myc and part of a novel gene named rlf in two small-cell lung cancer (SCLC) cell lines. The rlf-L-myc fusion gene is formed by intrachromosomal rearrangements placing the regulatory region and (at least) the first exon of rlf upstream of the L-myc gene. In the characterized cases the fusion gene has also been involved in DNA amplification. Here we report on a similar in vivo rearrangement involving rlf and L-myc in a primary SCLC tumor. In addition, we have found co-amplification of L-myc and rlf without visible rearrangements in either gene in three other SCLC tumors, confirming the physical linkage of these loci. PMID- 1312700 TI - Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma. AB - To clarify the incidence, timing and pathogenetic significance of p53 gene alterations in the progression of small-cell lung carcinoma (SCLC), 17 primary tumors, 13 metastases and nine cell lines from 27 patients were analysed by a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Allelic losses and mutations of the p53 gene were detected in 24 out of 25 informative cases (96%) and 23 out of 27 cases (85%) respectively. Simultaneous losses and mutations were detected in all 16 stage III-IV tumors, while these alterations were detected only in 3 of 6 stage I-II tumors. When allelic losses and/or mutations were detected in the primary tumors, the same alterations were always maintained in the process of metastasis. In three cases, identical p53 alterations were detected among different organ metastases. The mutations detected in five cell lines were also detected in the corresponding original tumors. These results suggest that the alterations of the p53 gene are common and early events, but probably not the first events, in the development of SCLC, and that these alterations are essential for the maintenance of malignant phenotypes in the progression of SCLC. PMID- 1312701 TI - Lack of immortalizing activity of a human papillomavirus type 16 variant DNA with a mutation in the E2 gene isolated from normal human cervical keratinocytes. AB - The oncogenic potential of a human papillomavirus type 16 (HPV16) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes. The HPV16 variant was able to extend the lifespan of, but failed to immortalize, human keratinocytes. It could however cooperate with an activated ras oncogene to transform primary rodent cells. Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein. DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional, but a deletion in the viral E2 open reading frame was detected. This truncated E2 only weakly stimulated transcription of the viral regulatory region. Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency. These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer. PMID- 1312702 TI - Active LINE-1 retrotransposons in human testicular cancer. AB - An antibody to the protein encoded by the first open reading frame of the human LINE-1 (L1Hs) element was used to examine immunohistochemically 59 formalin fixed, human testicular germ cell tumors. Six tumors were positive for L1Hs expression. In all cases the L1Hs-positive cells were epithelial and most had the very characteristic, undifferentiated appearance of embryonal carcinoma or yolk sac tumor cells. One L1Hs-positive tumor had metastasized to the lung and lymph nodes and the metastatic cells also expressed L1Hs. This is the first observation of widespread retrotransposon expression in human tissue. These observations raise the possibility that L1Hs-encoded proteins may function as oncoproteins in some cancers. PMID- 1312703 TI - Overexpression of H-ras oncogene induces resistance to the growth-inhibitory action of transforming growth factor beta-1 (TGF-beta 1) and alters the number and type of TGF-beta 1 receptors in rat intestinal epithelial cell clones. AB - In this report, we utilize rat intestinal cell (IEC-18) clones expressing an activated human H-ras gene to investigate the relationship between malignant transformation and growth control by transforming growth factor beta (TGF-beta). We demonstrate that clones expressing high levels of H-ras oncogene lose sensitivity to the growth inhibitory action of TGF-beta. The loss of sensitivity is related to the degree of H-ras expression and is shown to be a direct consequence of H-ras expression through the use of a clonal cell line with inducible expression of activated H-ras. Co-incident with the loss of growth inhibition, ras-expressing clones display an altered expression of TGF-beta binding proteins as detectable by [125I]TGF-beta cross-linking. While IEC-18 cells express type II (92 kDa) binding protein predominantly, H-ras expression induces a shift to predominantly type I (69 kDa) binding protein expression. PMID- 1312704 TI - Modified cases of chickenpox after varicella vaccination: correlation of protection with antibody response. AB - Four thousand forty-two healthy children and adolescents, ages 12 months to 17 years, were vaccinated with a single dose of live attenuated varicella vaccine (VARIVAX; Merck Sharp and Dohme Research Laboratories) containing approximately 1000 to 1625 plaque-forming units/dose during clinical trials conducted from 1987 to 1989. Clinical follow-up of vaccinees revealed that 2.1 and 2.4% of vaccinees developed modified cases of varicella in the first and second years, respectively, after vaccination. Most of those who developed varicella postvaccination had an attenuated illness, characterized by fewer lesions and a lower incidence of fever (greater than or equal to 100 degrees F, oral) than after natural infection. The likelihood of developing varicella postvaccination decreased (P less than 0.0001) as the 6-week postvaccination glycoprotein-based enzyme-linked immunosorbent assay titer increased. In addition the number of lesions in these cases tended to decrease (P = 0.07 for Year 1 and P = 0.02 for Year 2) as the 6-week glycoprotein-based enzyme-linked immunosorbent assay titer increased. Thus the 6-week postvaccination glycoprotein-based enzyme-linked immunosorbent assay titer can be used as a surrogate marker for protection from natural disease. PMID- 1312705 TI - [Interferon treatment in small-cell lung cancer]. AB - The article consists of an account of Finnish experience in the clinical use of natural, and to a lesser extent, recombinant alpha-interferon in the treatment of lung cancer, including the results of research into interferon treatment of small cell lung cancer carried out by the Lung Cancer Group at University Hospital, Helsinki. PMID- 1312706 TI - Evidence that a 1.6 kilobase region of Neurospora mtDNA was derived by insertion of part of the LaBelle mitochondrial plasmid. AB - The LaBelle mitochondrial plasmid hybridizes to a small region of the mtDNA of different Neurospora species. Here, we show that the region of homology encompasses 1385 bp of plasmid sequence and 1649 bp of mtDNA sequence. Several findings--that the region of homology is not found in the mtDNAs of other organisms, that it includes the C-terminus of the ORF encoding the plasmid DNA polymerase, and that the ORF sequence in the mtDNA is interrupted by insertions- suggest that the region was part of the plasmid that integrated into mtDNA prior to the divergence of Neurospora species. Since the LaBelle plasmid has been found in only one Neurospora strain, we infer that the plasmid was lost subsequently from most strains. The LaBelle plasmid is transcribed by the host Neurospora mitochondrial RNA polymerase and the major promoter is located upstream of the long ORF, within the region of homology to mtDNA. A promoter used for the transcription of the mitochondrial small rRNA is found at a corresponding position in Neurospora mtDNA and may have been acquired via integration of the plasmid sequence. Our results provide evidence that an autonomous infectious element may contribute to sequences that functionally constitute an organism's mtDNA. PMID- 1312707 TI - SfiI genomic cleavage map of Escherichia coli K-12 strain MG1655. AB - An SfiI restriction map of Escherichia coli K-12 strain MG1655 is presented. The map contains thirty-one cleavage sites separating fragments ranging in size from 407 kb to 3.7 kb. Several techniques were used in the construction of this map, including CHEF pulsed field gel electrophoresis; physical analysis of a set of twenty-six auxotrophic transposon insertions; correlation with the restriction map of Kohara and coworkers using the commercially available E. coli Gene Mapping Membranes; analysis of publicly available sequence information; and correlation of the above data with the combined genetic and physical map developed by Rudd, et al. The combination of these techniques has yielded a map in which all but one site can be localized within a range of +/- 2 kb, and over half the sites can be localized precisely by sequence data. Two sites present in the EcoSeq5 sequence database are not cleaved in MG1655 and four sites are noted to be sensitive to methylation by the dcm methylase. This map, combined with the NotI physical map of MG1655, can aid in the rapid, precise mapping of several different types of genetic alterations, including transposon mediated mutations and other insertions, inversions, deletions and duplications. PMID- 1312708 TI - Colorimetric detection of herpes simplex virus by DNA in situ sandwich hybridization: a rapid, formamide-free, random oligomer-enhanced method. PMID- 1312709 TI - A dinucleotide repeat polymorphism in the human Na+,K+ ATPase, alpha subunit (ATP1A3) gene. PMID- 1312710 TI - The initiation accuracy of the SV40 early transcription is determined by the functional domains of two TATA elements. AB - To locate the boundaries of the TATA element in the SV40 early promoter, point mutations have been constructed such as to cover the whole T + A-rich region of the replication origin. The effects of these mutations on the rate of transcription in vivo show that this region actually contains two TATA elements I and II, each independently directing the accurate initiation of transcription from a specified set of start sites, EES1 and EES2, respectively. The sequence of TATA element I fits best with the compiled 'consensus' sequence found in eukaryotic gene promoters and is the most efficient in directing transcription initiation. Mutations which improve this fit can still increase the rate of transcription, confirming the theory of a correlation between the nucleotide sequence of a TATA element and its functional efficiency. Moreover, some mutations which simultaneously modify the angle of DNA curvature in the T + A rich promoter region and the rate of transcription reveal a correlation between DNA bending and transcription initiation. PMID- 1312711 TI - Early hydrogen-bonding events in the folding reaction of ubiquitin. AB - The formation of hydrogen-bonded structure in the folding reaction of ubiquitin, a small cytoplasmic protein with an extended beta-sheet and an alpha-helix surrounding a pronounced hydrophobic core, has been investigated by hydrogen deuterium exchange labeling in conjunction with rapid mixing methods and two dimensional NMR analysis. The time course of protection from exchange has been measured for 26 back-bone amide protons that form stable hydrogen bonds upon refolding and exchange slowly under native conditions. Amide protons in the beta sheet and the alpha-helix, as well as protons involved in hydrogen bonds at the helix/sheet interface, become 80% protected in an initial 8-ms folding phase, indicating that the two elements of secondary structure form and associate in a common cooperative folding event. Somewhat slower protection rates for residues 59, 61, and 69 provide evidence for the subsequent stabilization of a surface loop. Most probes also exhibit two minor phases with time constants of about 100 ms and 10 s. Only two of the observed residues, Gln-41 and Arg-42, display significant slow folding phases, with amplitudes of 37% and 22%, respectively, which can be attributed to native-like folding intermediates containing cis peptide bonds for Pro-37 and/or Pro-38. Compared with other proteins studied by pulse labeling, including cytochrome c, ribonuclease, and barnase, the initial formation of hydrogen-bonded structure in ubiquitin occurs at a more rapid rate and slow-folding species are less prominent. PMID- 1312712 TI - YMXM motifs of IRS-1 define substrate specificity of the insulin receptor kinase. AB - Of 34 tyrosine residues in insulin receptor substrate 1 (IRS-1), 14 are adjacent to acidic residues, suggesting that they might be phosphorylation sites. Synthetic peptides corresponding to sequences surrounding these tyrosines were used as substrates of the insulin receptor kinase. Surprisingly six of these, each within YMXM motifs, were phosphorylated with greatest efficiency (Km, 24-92 microM; kcat/Km, 0.6-2.1 x 10(4) M-1.sec-1). Substituted YMXM peptides revealed a strong preference of the insulin receptor kinase for methionine at Y + 1 and Y + 3 positions. When phosphorylated, related YMXM sequences are recognition motifs for binding to proteins with src-homology (SH2) domains. The combined hydrophobic and flexible nature of methionine side chains adjacent to the targeted tyrosines provides a versatile contact for recognition by diverse proteins involved in signal transduction. PMID- 1312713 TI - Differentiation of multiple domains in the herpes simplex virus 1 protease encoded by the UL26 gene. AB - Previous studies have shown that the herpes simplex virus 1 gene UL26 encodes a 635-amino acid protease that cleaves approximately 20 amino acids from the carboxyl terminus of itself and of a 329-amino acid product of the UL26.5 gene. The results of studies with a variety of protease inhibitors showed that the UL26 protease was inhibited by serine protease inhibitors but not by inhibitors of cysteine protease, aspartic acid protease, or metalloprotease. Mutations resulting in amino acid substitutions, deletions, or insertion of stop codons in the gene or of 20-amino acid stretches into the protease have delineated the dispensable domains I and IV at the amino and carboxyl domains of the gene product. The essential carboxyl-proximal domain (III) can be separated from the essential amino-proximal domain (II) by at least 20 amino acids. The amino proximal domain is the most conserved region among varicella-zoster virus and human cytomegalovirus homologues of UL26. Of the conserved aspartic acid, histidine, or serine amino acids in this domain, only histidine-61 and -148 could not be replaced without impairment of the proteolytic activity. PMID- 1312714 TI - Homodimerization and constitutive activation of the erythropoietin receptor. AB - The erythropoietin receptor (EPO-R) is a member of the recently described cytokine receptor superfamily. A constitutively active (hormone independent) form of the EPO-R was isolated that has a single amino acid change in the exoplasmic domain, converting arginine-129 to cysteine (R129C). Since EPO-Rs containing R129S, R129E, and R129P mutations are functionally wild type, the presence of cysteine at residue 129, and not the loss of arginine, is required for constitutive activity. Several mutant forms of the EPO-R were analyzed; all constitutively active mutants form disulfide-linked homodimers, whereas EPO responsive or inactive forms of the receptor do not. Monomers and disulfide linked dimers of the constitutive receptor are present on the plasma membrane and bind EPO with a single affinity. Homodimerization of the EPO-R is likely to play a role in ligand-induced signal transduction, and disulfide-linked dimerization of the constitutive receptor may mimic this step. PMID- 1312715 TI - Thrombomodulin gene regulation by cAMP and retinoic acid in F9 embryonal carcinoma cells. AB - Thrombomodulin (TM) expression was investigated during differentiation of F9 embryonal carcinoma cells into primitive or parietal endoderm. Exposure of F9 cells to retinoic acid (RA) triggers differentiation into primitive endoderm and induces the appearance of barely detectable amounts of TM mRNA, whereas treatment with dibutyryl cAMP plus theophylline (CT) augments the levels of TM mRNA to a 4 fold greater extent than RA. Exposure of F9 cells to RA plus CT initiates differentiation into parietal endoderm and synergistically increases the levels of TM mRNA by 10- to 12-fold compared with CT. The time-dependent establishment of cooperativity between RA and CT appears to be secondary to RA-induced differentiation to primitive endoderm. The above alterations in TM mRNA levels occur by a transcriptional mechanism as judged by nuclear run-on experiments. Transient gene expression experiments show that the human TM promoter is transactivated by coexpression of the human RA receptor beta. Thus, the mechanism of induction of TM expression in F9 cells undergoing differentiation to parietal endoderm appears to be similar, but not identical, to that noted for other late response genes. PMID- 1312716 TI - Detection of intrahepatic replication of hepatitis C virus RNA by in situ hybridization and comparison with histopathology. AB - A nonisotopic in situ hybridization (NISH) assay was used to detect hepatitis C virus (HCV) RNA. A synthetic oligonucleotide complementary to bases 252-301 of the highly conserved 5' noncoding region of the HCV genome was end-labeled by terminal deoxynucleotidyltransferase using digoxigenin-conjugated dUTP. The hybridized oligomer was revealed by an immunohistochemical reaction after incubation with an alkaline phosphatase-conjugated anti-digoxigenin antibody and subsequent amplification with a complex of alkaline phosphatase and anti-alkaline phosphatase antibodies. The intracellular distribution of HCV RNA was monitored in the livers of two chimpanzees experimentally infected with the H strain of HCV and compared with the serum alanine aminotransferase activity, serum HCV RNA, and liver histopathology. Most cells were stained in the cytoplasm as early as 2 days after inoculation, 1 and 2 days, respectively, before the appearance of viral RNA in the serum. The time course of HCV RNA replication was correlated with increases in serum alanine aminotransferase. However, neither one paralleled the appearance of liver cell necrosis nor showed any correlation with the inflammatory response. The NISH signal was not found in liver biopsy specimens taken from these two animals before inoculation with HCV, from chimpanzees with acute hepatitis type A, B, or delta, or from two animals never experimentally infected with any hepatitis agent; moreover, it disappeared when the positive specimens were predigested with RNase and it was not observed after hybridization of positive controls with a labeled oligomer unrelated to HCV RNA. Thus, detection of liver HCV RNA by NISH is a sensitive and specific method for studying HCV replication at the cellular level. Intracellular replication of HCV did not appear to be associated with histopathologic changes in the liver, although the correlation with increases of liver enzyme activity in the serum suggested possible damage to the liver cell membrane. PMID- 1312717 TI - Multiple retinoid-responsive receptors in a single cell: families of retinoid "X" receptors and retinoic acid receptors in the Xenopus egg. AB - In a search for nuclear hormone receptors expressed in early development we found that Xenopus laevis eggs contain mRNAs from two retinoic acid receptor genes (xRAR alpha and xRAR gamma) and two retinoid "X" receptor genes (xRXR alpha and xRXR gamma). We also show that RXRs are members of a family of at least three genes, thus expanding the number of genes encoding retinoic acid-responsive transcription factors to six. With the exception of xRXR gamma, these maternal mRNAs are degraded before gastrulation. The RXRs isolated are differentially activated by retinoic acid and by 3,4-didehydroretinoic acid. Considered together, these four receptors provide a molecular basis for the pleiotropic effects of retinoic acid on early development, and their pattern of expression suggests a role for retinoic acid at the earliest stages of embryonic determination. PMID- 1312718 TI - Direct effects of luteinizing hormone-releasing hormone agonists and antagonists on MCF-7 mammary cancer cells. AB - The binding of luteinizing hormone-releasing hormone (LH-RH) analogues to the human mammary tumor cell line MCF-7 and their effect on the cell proliferation was studied to elucidate their direct action on estrogen-dependent mammary tumors. The growth rate of these cells was doubled by the addition of 1 nM estradiol to cells maintained in an estrogen-deficient medium. Although the basal growth rate was only slightly inhibited by the LH-RH antagonist [Ac-D-Nal(2)1,D Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), the estrogen-stimulated growth was completely abolished by the antagonist. In contrast, the LH-RH agonist buserelin stimulated cell growth in estrogen-deficient medium, whereas it had no effect in the presence of estrogen. 125I-labeled buserelin was used for the measurement of LH-RH receptors on MCF-7 cells. A Scatchard plot analysis of buserelin-specific binding revealed a nonlinear plot, which suggested the presence of one high-affinity binding site with a Kd of 1.4 +/- 1.0 nM and the remaining sites with low affinity (Kd = 1.3 +/- 1.0 microM). The binding of 125I labeled buserelin was displaced equally well by unlabeled buserelin and by the LH RH antagonist SB-75, suggesting that both analogues are bound to the same receptor. When parallel experiments were performed with 125I-labeled SB-75, the binding was displaced by unlabeled SB-75 and other antagonists, but only partially displaced by unlabeled buserelin. The results suggest that in these mammary tumor cells there is a LH-RH antagonist binding site that is not recognizable by LH-RH agonists. This hypothesis was tested by measuring cell growth in the presence of both agonists and antagonists. It was found that SB-75 inhibited the stimulation of growth by buserelin, but buserelin did not prevent the inhibition by the antagonist of the estrogen-dependent growth. These results suggest that antagonists directly inhibit mammary tumor growth, not only by competing with LH-RH high-affinity receptors, but also by other mechanisms mediated by low-affinity antagonist binding sites. PMID- 1312719 TI - The rat trk protooncogene product exhibits properties characteristic of the slow nerve growth factor receptor. AB - Two distinct nerve growth factor receptor (NGFR) complexes are present on NGF responsive cell types; these correspond to 100 kDa and 158 kDa for the fast (fNGFR) and the slow (sNGFR) NGFRs, respectively. Previous studies indicate that each complex is derived from a separate gene product and that the sNGFR contains tyrosine kinase activity. The cDNA encoding the fNGFR has previously been cloned. In this report, a rat trk protooncogene cDNA has been isolated from PC12 cells and Trk has been shown to bind NGF, generating a complex of 158 kDa. Characterization of NGF-Trk interactions indicates that Trk and NGF dissociate more slowly than do NGF and the fNGFR. Moreover, NGF-bound Trk is not destroyed by trypsin digestion whereas the NGF-fNGFR complex is sensitive to trypsin digestion. These observations suggest that the trk protooncogene product, expressed in the absence of the fNGFR, binds NGF with properties characteristic of the sNGFR, which was identified as the high-affinity NGFR on primary neurons and PC12 cells. PMID- 1312720 TI - Relaxin binding in the rat heart atrium. AB - Relaxin is a member of the insulin family of polypeptides that is best known as a reproductive hormone. In an effort to elucidate the mechanism of action of relaxin we previously localized the specific binding sites of a 32P-labeled relaxin in the rat uterus and brain. These studies suggested that, in addition to its classical role in pregnancy, relaxin might have other physiological functions. In the present paper we describe the specific and high-affinity binding of relaxin to the cardiac atrium of both male and female rats. The relaxin binding could not be displaced by peptides belonging to the same family [insulin, insulin-like growth factor I (IGF-I)] or by peptides that were identified in the atrium or were known to have cardiovascular functions (atrial natriuretic peptide, angiotensin II). The dissociation constant for relaxin in the atrium was estimated to be 1.4 nM, which was similar to that found in the uterus (1.3 nM) and the brain (1.4 nM). In view of the close association of relaxin with reproduction, an experiment was also performed to compare the relaxin binding in the uterus and heart after gonadectomy and sex steroid treatment. It was found that the relaxin binding in the rat uterus was diminished by 53% overall following ovariectomy but was restored to 90% of normal levels when treated with estrogen (but not with testosterone). In contrast, the relaxin binding in the rat heart was not affected by castration or sex steroid treatment. We conclude that specific and high-affinity relaxin receptors exist in the atrium of both the male and female rat heart and that these are regulated differently than the relaxin receptors in the uterus. PMID- 1312721 TI - Crystal structure of the neutral form of fructose 1,6-bisphosphatase complexed with regulatory inhibitor fructose 2,6-bisphosphate at 2.6-A resolution. AB - The three-dimensional structure of the complex between fructose 1,6 bisphosphatase (EC 3.1.3.11) and the physiological inhibitor beta-D-fructose 2,6 bisphosphate (Fru-2,6-P2), an analogue of the substrate (fructose 1,6 bisphosphate), has been refined at 2.6-A resolution to a residual error (R) factor of 0.171. The rms deviations are 0.012 A and 2.88 degrees from ideal geometries of bond lengths and angles, respectively. The Fru-2,6-P2 occupies the active sites of both polypeptides C1 and C2 in the crystallographic asymmetric unit in the space group P3(2)21. The furanose and 6-phosphate of Fru-2,6-P2 are located at the fructose 6-phosphate site established earlier, and the 2-phosphate binds to the OH of Ser-124, the NH3+ of Lys-274, and the backbone NH of Gly-122 and Ser-123. Backbone displacements of 1 A occur for residues from Asp-121 to Asn 125. Model building of substrate alpha-D-Fru-1,6-P2 based on the binding structure of Fru-2,6-P2 in the active site shows interactions of the 1-phosphate with the backbone NH of Ser-123 and Ser-124. In the AMP sites, density peaks attributed to Fru-2,6-P2 are seen in C1 (and C4) but not in C2 (and C3). This minor binding of Fru-2,6-P2 to AMP sites partially explains the synergistic interaction between AMP and Fru-2,6-P2 and the protection of the AMP site from acetylation in the presence of Fru-2,6-P2. In the synergistic interaction between AMP and Fru-2,6-P2, inhibition of catalytic metal binding by the presence of Fru 2,6-P2 at the active site, and propagation of structural changes over some 28 A along beta-strand B3 from residues 121 to 125 in the active site to Lys-112 and Tyr-113 in the AMP site, as well as movement of helices across the interdimeric interfaces, may affect AMP binding and the subsequent R-to-T transition. In addition, occupancy of Fru-2,6-P2 at the AMP sites of C1 and C4 may favor binding of AMP to the remaining unoccupied AMP sites and thus promote the accompanying quaternary conformational changes. PMID- 1312722 TI - Three-dimensional structure of Theiler murine encephalomyelitis virus (BeAn strain). AB - Depending on the strain, Theiler murine encephalomyelitis virus (TMEV) may cause acute encephalitis or chronic demyelinating disease, which is associated with viral persistence in mice. Persistent central nervous system infection and demyelination by the less-virulent TMEV has provided a useful animal model for the human demyelinating disease multiple sclerosis. The less-virulent BeAn strain of TMEV was crystallized and its atomic structure was determined by x-ray crystallography. The alpha-carbon coordinates of the closely related Mengo virus were used to calculate the initial phases to 3.5 A resolution and the interpretable electron density map was produced by 10 cycles of 30-fold noncrystallographic molecular replacement averaging. The structure revealed a high degree of overall structural similarity to Mengo virus as well as substantial differences in the surface loops. These structural changes might be correlated with TMEV host-specific recognition, pH-related stability, and neurovirulence. PMID- 1312723 TI - Differential low density lipoprotein receptor-dependent formation of eicosanoids in human blood-derived monocytes. AB - We studied the ability of low density lipoproteins (LDLs) to provide arachidonic acid (AA) for eicosanoid biosynthesis in human blood-derived monocytes. When incubated in the presence of reconstituted LDL that contained cholesteryl [1 14C]arachidonate (recLDL-[14C]AA-CE), resting monocytes formed three labeled products of the prostaglandin (PG) H synthase pathway: 6-keto-PGF1 alpha, thromboxane B2, and PGE2. The amounts of these eicosanoids in response to recLDL [14C]AA-CE were comparable to or exceeded those that were produced in response to the addition of 10 microM unesterified [1-14C]AA. By contrast, resting monocytes formed only small amounts of products of the 5-lipoxygenase pathway, leukotriene (LT) B4 and LTC4 from either recLDL-[14C]AA-CE or [14C]AA, indicating preferential utilization of AA in the PGH synthase reaction. However, they converted LDL-derived [14C]AA efficiently into LTB4 and LTC4, when they were first incubated with recLDL-[14C]AA-CE and subsequently stimulated with the chemotactic peptide N-formylmethionylleucylphenylalanine or the Ca2+ ionophore A23187. The classical LDL receptor pathway mediated the synthesis of all of the above eicosanoids from LDL but not from unesterified AA. These results demonstrate that the LDL receptor pathway preferentially promotes the synthesis of PGH synthase products in resting human blood-derived monocytes and that an additional mechanism is required to promote effective synthesis of 5-lipoxygenase pathway products from AA that originates in LDL cholesteryl esters. PMID- 1312724 TI - Regulatory genes linked to the albino locus in the mouse confer competence for inducible expression on the structural gene encoding serine dehydratase. AB - A cluster of unlinked genes encoding gluconeogenic enzymes in the mouse is characterized by the failure of normal hormone-inducible expression in animals homozygous for one of several overlapping deletions mapping on chromosome 7 near the albino locus. Previous investigations have shown hormones and their receptors to be normal in the mutants and therefore not responsible for the abnormalities of inducibility. Instead, these studies have implicated a possible failure of the affected structural enzyme genes themselves to attain during prenatal development the competence for inducible gene expression. The results reported here add serine dehydratase (EC 4.2.1.13) and its structural gene to the affected group of gluconeogenic enzymes and their genes. Even though, in deletion homozygotes, serine dehydratase is expressed normally on the constitutive level, hormone inducible expression fails to develop. The abnormality appears to reside in a defect of prenatal differentiation of cis-acting regulatory elements of the structural gene essential in the pathway of inducible gene expression. PMID- 1312726 TI - Production of high efficiency of plating hepatitis A virus in primary African green monkey kidney cells. AB - High-titered hepatitis A virus, strain HM-175, was produced in primary African green monkey kidney cells (5.5 x 10(10) tissue culture ID50/850 cm2 roller bottle). The virus preparation had an efficiency of plating of 15 particles per infectious unit. Single-cycle growth kinetics of the adapted virus indicated that after an eclipse period of 2 days, maximal yields were attained 6 days after infection. PMID- 1312725 TI - Absolute requirement for GTP in activation of human neutrophil NADPH oxidase in a cell-free system: role of ATP in regenerating GTP. AB - Guanine and/or adenine nucleotides appear to be involved in the activation of the superoxide-generating NADPH oxidase of phagocytic cells. Their precise roles, however, are unclear, as much of the evidence for their involvement comes from experiments in which nucleotides have been added to complex systems already rich in both endogenous nucleotides and enzymes capable of interconverting them. To circumvent this problem we have examined the role of nucleotides in neutrophil NADPH oxidase activation by using a cell-free system in which adenine and guanine nucleotide concentrations were carefully controlled and monitored by (i) depletion of endogenous nucleotides by extensive dialysis and charcoal treatment; (ii) reconstitution of the depleted system with reagents analyzed for purity; and (iii) measurement of nucleotide levels in cytosol preparations and in oxidase reaction mixtures by HPLC analysis. In contrast to previous reports that have demonstrated only a several-fold enhancement of oxidase activity by GTP or its analogs, we have shown that oxidase activation was absolutely dependent upon GTP in reactions containing dialyzed cytosol in which the total endogenous nucleotide levels were reduced by greater than 99.5%. Kinetic studies revealed that GTP is required at or before the rate-limiting step in oxidase activation. Two nonhydrolyzable analogs of GTP, guanosine 5'-(gamma-thio)triphosphate and guanylyl imidodiphosphate, were even more active than GTP, suggesting the involvement of one or more GTP-binding proteins. In contrast, ATP was neither necessary nor sufficient for oxidase activation. If reaction mixtures were contaminated with GDP and/or GMP, however, ATP (but not its nonhydrolyzable analog adenylyl imidodiphosphate) could indirectly support oxidase activation by means of endogenous enzymes that catalyze the ATP-dependent conversion of GMP and GDP to GTP. PMID- 1312727 TI - Stimulation of vascular Na-K pump with subpressor angiotensin II in rats. AB - The effect of subpressor doses of angiotensin II (ANG II) on vascular Na-K pump activity and Na-H exchange, two transmembrane signals of trophic stimulation of vascular muscle, was investigated. Male Sprague-Dawley rats (350-400 g) were given subpressor doses of ANG II by osmotic minipump intraperitoneally for 24 hr or 7-10 days. Control rats received sham procedure/vehicle infusion. Na-K pump activity (86Rb uptake), total and intracellular (Li exchange at 4 degrees C) Na content, and amiloride-sensitive and -insensitive Na uptake of aortas were measured ex vivo. Ouabain-sensitive 86Rb uptake of aortas of rats receiving 80 100, 160-180, and 240-260 ng/kg.min-1 of ANG II for 24 hr was 26.6 +/- 3.5, 28.8 +/- 3.4, and 29.1 +/- 2.6 nmol/mg dry wt.15 min-1 (mean +/- SD, n = 7-12), respectively, compared with 25.2 +/- 3.8 in controls (n = 23, P less than 0.01). These increases were maintained at 7-10 days. After 24 hr and 7-10 days of ANG II treatment, the total Na content of aortas was increased by 9.2% (P less than 0.01) and 7.6% (P less than 0.02), respectively, without a change in intracellular Na content, indicating accumulation of excess extracellular Na. Total and amiloride-sensitive Na uptake of the aorta was unchanged after 24 hr or 7-10 days of ANG II administration. The dry weight of anatomically defined segments of the aorta was 40 +/- 3.8 mg/kg body wt (n = 25) after 24 hr and 42 +/ 4.4 (n = 20) after 7-10 days of ANG II administration, compared with 37 +/- 4.8 (n = 15, P less than 0.05) and 37 +/- 4.9 (n = 17, P less than 0.01) in appropriate controls. Increased Na-K pump activity may signal the onset of trophic stimulation of vascular muscle by ANG II. PMID- 1312728 TI - Blockade of conditioned taste aversion by scopolamine and N-methyl scopolamine: associative conditioning, not amnesia. AB - The anticholinergic, scopolamine, consistently disrupts one-trial passive avoidance conditioning but the effects of such drugs on one-trial conditioned taste aversion (CTA) are variable and contradictory. In the present study, treatment of rats with scopolamine impaired the suppression of sucrose intake by post-ingestion administration of lithium chloride (LiCl) in a two-bottle choice test. A similar effect was obtained by using N-methyl scopolamine which penetrates the brain only to a limited degree on acute administration. The blockade of CTA could be prevented in three ways: (i) by exposing the rats to sucrose only on the training day, (ii) by pre-exposing the rats to both sucrose and scopolamine, and (iii) by using a less palatable sucrose/ascorbate mixture. The results demonstrate that the effect of scopolamine on taste aversion is not mediated by the central nervous system, and can be modified by altering the novelty and relative salience of the taste conditioned stimulus. These experiments suggest that conditioned associations between taste and LiCl, and scopolamine and LiCl may underlie the blockade of CTA by scopolamine. PMID- 1312729 TI - Spinal cord alpha-2 noradrenergic receptors mediate conditioned analgesia. AB - The present experiment investigated the effects of direct spinal administration of the monoaminergic receptor blockers yohimbine, phentolamine and methysergide on the expression of conditioned analgesia. Animals in the Paired group received classical conditioning trials in which one context was paired with footshock administration (1 mA shock for 15 s). Animals in the Unpaired control group were administered shock in a second, different, context. On the test day animals within each condition were administered saline (20 microliters), yohimbine (30 micrograms), phentolamine (30 micrograms), or methysergide (30 micrograms) prior to receiving a hot plate test (50 degrees C) in the context previously used to shock the Paired group. These ligands were administered into the spinal fluid through a chronic, indwelling spinal catheter. Animals in the Paired group which received saline displayed longer paw lick latencies than saline-treated animals in the Unpaired group. Yohimbine, but not phentolamine or methysergide, attenuated this conditioned analgesia. These results suggest that spinal cord noradrenergic substrates mediate conditioned analgesia, and that this mediation occurs specifically through the alpha-2 noradrenergic receptor. PMID- 1312730 TI - Cocaine facilitation of prefrontal cortex self-stimulation: a microstructural and pharmacological analysis. AB - A novel self-stimulation methodology involving a fixed-interval (FI-5 s) schedule of reinforcement, microanalysis and threshold evaluation was used to investigate the effects of cocaine on rats lever pressing for electrical stimulation of the prefrontal cortex. Cocaine (15 mg/kg) increased medial prefrontal cortex (MPC) self-stimulation rates under FI-5 by a mean of 269% and reduced current thresholds for self-stimulation. A similar facilitation was evident with self stimulation of the sulcal prefrontal cortex. Microanalysis showed that cocaine decreased inter-response times and post-reinforcement pauses, increased responding in the second and third quartiles of the inter-reinforcement interval (IRI) and decreased responding in the fourth IRI quartile. Schedule control of responding was still evident following cocaine despite the profound facilitation of response rates. Increased response rates were seen up to 48 h following a single dose of cocaine, suggesting sensitization of the PFC reinforcement substrate. The acute effects of cocaine on MPC self-stimulation were completely reversed by the dopamine (DA) D1 antagonist SCH 23390 0.02 mg/kg) and the D2 antagonist raclopride (0.3 mg/kg) but not by naloxone (0.5 mg/kg). These results are consistent with previous studies demonstrating the PFC as part of the neural substrate mediating cocaine reward. Further, these results implicate DA receptors in the reinforcing properties of both cocaine and MPC self-stimulation. PMID- 1312731 TI - Infantile stimulation and the role of the benzodiazepine receptor system in adult acquisition of two-way avoidance behavior. AB - The present study shows that postnatal "consistent" handling (CH) of rats had long-lasting improving effects on coping with an stressful task (i.e. two-way active avoidance), and that such effects were partially prevented by acute Ro 15 1788 (antagonist of benzodiazepine receptor-BZR; 5 mg/kg) administration. Long lasting detrimental effects in the same task were also observed in rats which received postnatal "inconsistent" handling (INCH), effects that were slightly increased by acute Ro 15-1788 treatment. Finally, Ro 15-1788 tended to increase avoidance acquisition in non-handled (NH) animals. The observed effects of Ro 15 1788 could be partially attributed to a differential modulation of the process of avoidance acquisition depending on postnatal treatments producing different levels of emotionality. PMID- 1312732 TI - Down-regulation of cortical beta-adrenoceptors by chronic treatment with functional NMDA antagonists. AB - Down-regulation of cortical beta-adrenoceptors is observed in laboratory animals following chronic treatment with many clinically effective antidepressant therapies. [3H]Dihydroalprenolol (DHA) binding to cortical beta-adrenoceptors was examined in mice treated with the functional NMDA antagonists 1-aminocyclopropane carboxylic acid (ACPC) and MK-801. ACPC and MK-801 reduced [3H]DHA binding by 19 (P less than 0.05) and 21% (P less than 0.05), respectively, while imipramine produced a 23% (P less than 0.05) reduction. No corresponding changes in the KD of [3H]DHA were observed. These findings are consistent with the observation that functional NMDA antagonists are active in animal models commonly used to evaluate antidepressants and may represent a novel approach to the treatment of depression. PMID- 1312733 TI - Breast cancer recurrence after lumpectomy and irradiation: role of mammography in detection. AB - Between 1977 and 1989, 102 of 1,145 patients treated with lumpectomy and radiation as an alternative to mastectomy required subsequent biopsy for suspected ipsilateral recurrence. The authors reviewed the mammograms of 58 of those patients for whom at least two sets of mammograms were available, including one set obtained within 3 months of the subsequent repeated biopsy. Of 38 biopsy proved recurrences, 13 (34%) were detected with mammography alone, 17 (45%) with palpation alone, and eight (21%) with both mammography and palpation. While standard mammographic criteria for biopsy were followed, distortions and calcifications inherent to posttreatment appearances necessitated judicious modifications. As anticipated, sensitivities and positive predictive values showed more impairment within the lumpectomy quadrant. In addition, all cases of purely in situ cancer were detected solely with mammography. Mammography plays an important complementary role to physical examination in posttreatment follow-up. On the basis of these findings, a follow-up algorithm for the ongoing evaluation of these patients was developed. PMID- 1312734 TI - Multisection FLASH: method for breath-hold MR imaging of the entire liver. AB - One hundred ten patients with various focal liver lesions were imaged with a multisection fast low-angle shot (FLASH) gradient-echo sequence with an echo time of 4.6 msec. This sequence enabled the acquisition of 19 T1-weighted magnetic resonance (MR) images of the liver within a single 26-second breath hold. Patients were also examined with standard T1- and T2-weighted spin-echo (SE) sequences. The multisection FLASH sequence provided significantly higher (P less than .01) liver-spleen contrast, liver-spleen signal-difference-to-noise ratio (SD/N), liver-tumor contrast, and liver-tumor SD/N than the T1-weighted SE sequence but lower values than the T2-weighted SE sequence. Motion artifacts were reduced with the multisection FLASH sequence compared with both SE sequences (P less than .01). The overall image quality of the multisection FLASH images was similar to that of the T1-weighted SE images and superior to that of T2-weighted SE images. The most important characteristics of the multisection FLASH technique in MR imaging of the liver are the high T1 contrast, the prevention of motion artifacts, and a dramatic reduction in imaging time. PMID- 1312735 TI - Mucin-producing pancreatic tumor: CT findings and histopathologic correlation. AB - Twenty patients with mucin-producing pancreatic tumor and 60 with other pancreatic diseases underwent computed tomography (CT) to establish the CT characteristics of mucin-producing pancreatic tumor. Scans were obtained with thin sections by administering a large volume of contrast material (200 mL). Mucin-producing pancreatic tumors were divided into three subgroups, and the CT characteristics were as follows: Main duct type tumors consisted of a cystic mass in or communicating with the dilated main pancreatic duct (MPD). Excrescent nodules and/or septa were found in the cyst. The MPD was markedly dilated over its entire length. Branch duct type tumors consisted of clustered small cysts that were all approximately the same size in diameter (1-2 cm). Excrescent nodules or septa were not always seen. The MPD near the lesion was often slightly dilated. Peripheral type tumors consisted of a well-defined cystic mass with excrescent nodules and/or septa. Even if the cyst was multilocular, a large main cyst was in it. The MPD usually was not dilated. The CT findings corresponded to macroscopic findings. Mucin-producing pancreatic tumor can be differentiated from other pancreatic diseases with these criteria. PMID- 1312736 TI - Adenocarcinoma of the pancreatic ducts: comparative evaluation with CT and MR imaging at 1.5 T. AB - A prospective comparison of computed tomography (CT) and magnetic resonance (MR) imaging at 1.5 T was performed in 50 patients with the suspected diagnosis of pancreatic carcinoma. CT scans were obtained before and after administration of contrast material in 41 of 50 patients (82%); 34 of 41 postcontrast scans (83%) were obtained with dynamic CT. MR images were interpreted without knowledge of the results of CT, ultrasound, cholangiography, or endoscopic retrograde cholangiopancreatography in 48 patients (96%). Surgical correlation of findings at CT and MR imaging was performed in 24 patients (48%) at laparotomy and in two patients (4%) at autopsy. On T1-weighted MR images, relatively diminished signal intensity of tumor compared with that of the adjacent pancreas was a consistent finding. MR imaging proved superior to CT in identification of pancreatic carcinoma (particularly in smaller intrapancreatic tumors), peripancreatic extension, vascular and portal vein invasion, and duodenal invasion. These results suggest that MR imaging of the pancreas is superior in many instances to CT in preoperative evaluation of pancreatic carcinoma. PMID- 1312737 TI - ENDOR and EPR of metalloproteins. PMID- 1312738 TI - [Application of protein engineering to drug design]. PMID- 1312739 TI - Sodium transport and its regulation. Festschrift for Professor Isidore S. Edelman. PMID- 1312740 TI - Steroid receptors: distribution along the nephron. PMID- 1312741 TI - Regulation of Na+ permeability by aldosterone. PMID- 1312742 TI - Regulation of apical membrane Na and K channels in rat renal collecting tubules by aldosterone. PMID- 1312743 TI - Regulation of Na+,K(+)-ATPase expression by thyroid hormone. PMID- 1312744 TI - Differential regulation of sodium pump isoforms in heart. PMID- 1312745 TI - Regulation of Na+,K(+)-ATPase by aldosterone. PMID- 1312746 TI - Thyroidal and steroidal regulation of Na+,K(+)-ATPase. PMID- 1312747 TI - Ionic regulation of Na+,K(+)-ATPase expression. PMID- 1312748 TI - Regulation of Na+,K(+)-ATPase in hypertension. PMID- 1312749 TI - FBI investigates leaks at OSI. PMID- 1312750 TI - Immunoglobulin A-induced shift of Epstein-Barr virus tissue tropism. AB - Increased immunoglobulin A (IgA) antibodies to the Epstein-Barr virus (EBV) appear months to years before the clinical onset of nasopharyngeal carcinoma and define populations at high risk for this EBV-associated epithelial cancer common in south China. In the human HT-29 epithelial cell line, polymeric IgA (pIgA) specific for EBV promoted infection of the otherwise refractory epithelial cells. When bound to pIgA, EBV entered epithelial cells through secretory component mediated IgA transport but no longer infected B lymphocytes. Such an immune induced shift in EBV tissue tropism provides a paradigm for endogenous spread of EBV in the immune host that predicts infectious sequelae of epithelium. PMID- 1312751 TI - Cold-preserved rat liver viability testing by proton nuclear magnetic resonance relaxometry. AB - The results of a series of experiments in the cold-preserved rat liver, applying a newly developed method of pretransplant viability testing, are described. The livers were stored either under simple hypothermic conditions (KHB) or in EC, HTK, or UW preservation solution. Livers were stored up to 48 hr and reperfused after a period of hypothermic storage of 1, 7, 14, or 21 hr. In a parallel series of experiments, with livers stored under identical conditions, repeated proton relaxometry measurements (0, 1, 7, 14, 24, 32, 48 hr) were undertaken; and ATP, ADP, AMP (Atkinson's energy charge), and water content of livers, as well as pH of storage solution, were estimated. Based on a strong correlation between proton spin-spin relaxation time T2 and tissue water content (edema), this new method may be useful to estimate the amount of cell swelling during hypothermic storage from a surgical biopsy of about 200 mg within a few minutes. There was, however, no significant correlation found between energy charge and/or pH and water content, T2, or bile flow. Our method could be useful as a rapid test method in experimental cold liver storage models and may be of interest in human liver transplantation as a viability indicator in combination with other parameters. PMID- 1312752 TI - A comparison of triple-therapy with double-therapy immunosuppression in cadaveric renal transplantation. AB - Triple-therapy (low-dose cyclosporine-azathioprine-prednisone) immunosuppression regimen was compared with double-therapy (cyclosporine-prednisone) in 91 consecutive nonrandomized adult cadaveric renal transplant recipients. Both groups were comparable with respect to ethnic diversity, prior transplants, and diabetes. The majority of patients with delayed function (ATN) were maintained on triple therapy, and the use of antilymphocyte agents was more common in the triple-therapy group (52% vs. 7%; P = 0.0001). Triple-therapy patients experienced increased acute rejection episodes (1.4 vs. 0.8 per patient, P = 0.03), required more courses of additional steroid pulse therapy (4.3 vs. 1.6 per patient; P = 0.001), and developed serious infections more frequently (37% vs. 15%; P = 0.05), especially CMV infections (17% vs. 0; P = 0.03), compared with double-therapy patients. However, the increased overall infection rate and CMV infection rate were observed only in those patients who received antilymphocyte agents compared with those who did not (46% vs. 21%; P = 0.02 for all infections, 26% vs. 4%; P = 0.006 for CMV). Additional steroid pulse therapy was associated with increased CMV infections (24% vs. 0; P = 0.03) but not with overall infections. One-year allograft and patient survival were equivalent in both groups. Exclusion of ATN patients from analysis did not alter the findings. This experience confirms the overall efficacy of triple-therapy immunosuppression in renal transplant recipients but suggests that triple therapy may be associated with more acute rejection episodes, greater immunosuppression requirements, and a resultant increase in infections, especially CMV. PMID- 1312753 TI - Serum levels and receptor expression of tumor necrosis factor-alpha following human allogeneic and autologous bone marrow transplantation. AB - We have investigated tumor necrosis factor-alpha levels in serum samples of patients before and after allogenic (16 patients) or autologous (8 patients) bone marrow transplantation. A sensitive immunoradiometric assay for monitoring levels of endogenous tumor necrosis factor-alpha was used. The serum levels of tumor necrosis factor-alpha were found to be relatively low (ranging from less than 15 to 77 pg/ml). Among 13 patients having graft-versus-host disease following allogeneic bone marrow transplantation 8 patients did not have detectable tumor necrosis factor-alpha (less than 15 pg/ml) while 4 out of 8 patients undergoing autologous bone marrow transplantation had detectable tumor necrosis factor-alpha levels (15 pg/ml), indicating a lack of correlation between tumor necrosis factor alpha serum levels and the occurrence of graft-versus-host disease. Because the tumor necrosis factor-alpha levels detected in patient sera could be regulated by TNF-receptor expression, the presence of TNF-receptor on patients' peripheral blood mononuclear cells was also studied using fluorescent liposome-conjugated tumor necrosis factor-alpha and immunofluorescence analysis. Our data indicate that peripheral blood mononuclear cells of some patients receiving either autologous or allogeneic bone marrow transplantation expressed significant levels of TNF-receptors, suggesting a lack of correlation between TNF-receptor expression and graft-versus-host disease development. PMID- 1312754 TI - Amyloid enhancing factor activity is associated with ubiquitin. AB - Crude amyloid enhancing factor (AEF) drastically reduces the pre-amyloid phase on passive transfer and induces amyloid deposition in the recipient mice in 48-120 h. We attempted to purify AEF from murine amyloidotic liver and spleen extracts by using gel filtration, preparative sodium dodecyl sulphate-polyacrylamide gel electrophoresis and ion exchange chromatography and isolated a 5.5 kDa peptide. In the mouse bioassay, this peptide induced accelerated splenic AA deposition in a dose-dependent manner. Based on structural, electrophoretic and immunochemical criteria the peptide was identified as ubiquitin. A polyclonal rabbit anti-bovine ubiquitin IgG antibody (RABU) abolished the in vivo AEF activity of crude murine AEF in a dose-dependent manner. Monomeric ubiquitin and its large molecular weight adducts were isolated from crude AEF using cyanogen bromide-activated sepharose conjugated to RABU and size exclusion chromatography methods. These were assayed and were found to possess AEF activity. Furthermore, increased levels of ubiquitin, a phenomenon similar to that of AEF, were detected by immunocytochemistry in mouse peritoneal leucocytes prior to and during amyloid deposition. Since AEF shares a number of biological and functional properties with ubiquitin, we suggest a possible role of ubiquitin as an AEF, and that serum amyloid protein A and ubiquitin, the two reactants generated during inflammatory stress conditions, may converge to induce AA amyloid deposition. PMID- 1312755 TI - Translation of potato virus S RNA in vitro: evidence of protein processing. AB - RNA from potato virus S (PVS), a member of the carlavirus group, was translated in vitro in rabbit reticulocyte lysate. Time-course experiments revealed the largest product of Mr 190 kD, decreasing in intensity after 60-min incubations, correlating with the accumulation of a 150-kD peptide. This apparent processing could be blocked by the addition of the amino-acid analogues p fluorophenylalanine and L-canavanine for phenylalanine and arginine, respectively. L-canavanine also appeared to specifically reduce the quantity of PVS (34 kD) coat protein, concomitant with the synthesis of a 36-kD peptide. Sucrose gradient-fractionated genomic RNA directed the synthesis of predominantly 190-kD peptides that appeared not to be processed in the absence of small molecular weight (subgenomic) RNA products. PMID- 1312756 TI - Conservation of amino-acid sequence motifs in lentivirus Vif proteins. AB - The nonstructural/regulatory genes of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses are believed to play an important role in the replication and pathogenesis of these viruses. In HIV-1 and other lentiviruses, the vif (viral infectivity factor) open reading frame (ORF) (also termed sor or Q in some lentivirus genomes) is located in the central region, overlapping the 3' end of the pol ORF, but in a different reading frame. Among the lentiviruses, only equine infectious anemia virus lacks a vif ORF. The predicted Vif protein sequences from 38 lentiviruses were analyzed for the presence of global and local sequence similarity. The Vif proteins of closely related lentiviruses are highly conserved (HIV-1HXB2:HIV-1mn = 91% identity), while those of more distantly related lentirviruses have diverged significantly (HIV-1HXB2:simian immunodeficiency virusmax = 30% identity). A search for local sequence similarity revealed that a unifying feature of predicted lentivirus Vif proteins is the presence of at least one of two short, highly conserved sequence motifs, SL(I/V)X4YX9Y and SLQXLA. SLQXLA was present in 34 of 38 lentiviruses examined, while the remaining four lentiviruses had one (three viruses) or two (one virus) substitutions in this motif (of five total substitutions, three were conservative changes). The SL(I/V)X4YX9Y motif was found only in primate lentiviruses and in bovine immunodeficiency-like virus. Based on these findings, we suggest that the locus designation vif be used to denote all lentivirus ORFs previously called vif, Q, or sor. PMID- 1312757 TI - [Chemonucleolysis using chymopapain and collagenase. 3-year results of a prospective randomized study]. AB - 100 patients were prospectively and randomized treated by chemonucleolysis either by collagenase (n = 50/400 ABC-U/disc) or by chymopapain (n = 50/4000 I.U.). The success rate after 1 year was 70% for collagenase and 78% after chymopapain, and 72%/80% after 3 years, respectively. Successful results increased significantly during the first year after treatment and remained stable after that point. After chymopapain, one case of successfully treated anaphylaxis (2%) occurred. After collagenase, 3 cases of secondary sequestrations were observed in cases with primarily closed discograms with intact dorsal longitudinal ligament. PMID- 1312758 TI - A comparison of simultaneous cervical cytology, HPV testing, and colposcopy. AB - This pilot study explores the screening techniques for premalignant and malignant disease of the cervix. Given current knowledge of the etiology and progression of cancer of the cervix, should family physicians screen patients with Papanicolaou (Pap) smears, Human Papillomavirus (HPV) smears, colposcopy, or some combination of these three? In a retrospective audit of 75 patients comparing simultaneous Pap smears and colposcopy, 5 of 8 patients with biopsy-proven cervical intraepithelial neoplasia (CIN) and one with invasive cancer had normal Pap smears. Because of this high false-negative Pap smear rate, a prospective study comparing a simultaneous Pap smear, HPV smear, and colposcopic examination (with biopsy when indicated) was undertaken. Seventy consecutive patients seen by the author for routine pelvic examinations consented to and were enrolled in the study. Seven patients had biopsy-proven CIN lesions; 2 were found by Pap smear, 3 by colposcopy, and 5 by HPV smear. The Pap smear missed 5 lesions, colposcopy missed 4, and the HPV smear missed 2. Further studies are needed to determine the optimal screening method for CIN. PMID- 1312759 TI - Colposcopy in family practice: pilot studies of pain prophylaxis and patient volume. AB - In a family practice office with volume representative of an average one-person practice, the implementation of colposcopy services was studied. During six months, 257 patients received Papanicolaou (PAP) smears. These patients represented 16.2% of the total 1,585 female patient visits for ages greater than 16. Of the 257 cytology specimens, 10.1% (26) revealed dysplasia or evidence of Human Papilloma Virus (HPV), indicating the need for colposcopic examination. Pathology reports of all biopsied cases confirmed the presence of dysplasia or HPV. These results suggest that the average family physician might reasonably anticipate about 100 colposcopy sessions per year, assuming each patient receives a diagnostic and a therapeutic colposcopic evaluation. In the course of colposcopy services in a family practice, 46 patients underwent 67 colposcopic examinations with cervical biopsy and/or cryotherapy in the office. Some patients received nonsteroidal anti-inflammatory medication 30-60 minutes before the procedure, with selection according to physician preference. All patients rated the pain experienced during the procedure on a 10-point visual-analog scale. Pain scores were significantly lower in those who received medication. Overall, patients tolerated the procedure well and there were no reported complications. Because of the possibility of such factors as the placebo effect influencing these results, a randomized, placebo-controlled, double-blind study will be needed to verify the findings. PMID- 1312760 TI - Glucocorticoids decrease vitamin D receptor number and gene expression in human osteosarcoma cells. AB - The mechanisms by which glucocorticoids (GC) inhibit some actions of vitamin D [1,25-(OH)2D3] are not well understood, but there is growing evidence that GC alter vitamin D receptor (VDR) number. We studied the effects of dexamethasone (DEX) on VDR number and mRNA in the human osteosarcoma cell line, MG-63. The effects of DEX on 1,25-(OH)2D3 binding were examined by incubating confluent cells overnight in media without or with 10(-6) M DEX. DEX decreased VDR number (B max) by approximately 70% (110 versus 32 fmol/mg cellular protein, p less than 0.001) without significantly changing the apparent affinity (K'D) of 1,25-(OH)2D3 for its receptor (3.8 versus 2.2 x 10(-10) M, p greater than 0.05). Overnight incubation of MG-63 cells with DEX produced a time- and dose-responsive decrease in VDR mRNA compared to untreated controls (p less than 0.01). To determine the mechanism of the DEX-mediated decrease in VDR mRNA, the effect of DEX on VDR mRNA stability was studied. We found that the half-life for the VDR mRNA was approximately 5.7 h and was not significantly changed when the cells were incubated with DEX (approximately 6.3 h). We conclude that DEX decreases both VDR number and mRNA in MG-63 osteosarcoma cells. Since the half-life of VDR mRNA was not significantly modified by dexamethasone, glucocorticoids appear to decrease VDR mRNA by inhibiting VDR gene transcription or by affecting the processing of VDR mRNA. PMID- 1312761 TI - Assessment of immune modulation of beta-adrenergic pathways in human dilated cardiomyopathy: influence of methodologic factors. AB - Sera from patients with dilated cardiomyopathy contain autoantibodies modifying cardiac beta-adrenergic pathways. The influence of the methodology used to determine the prevalence of these antibodies was examined by comparing in 51 patients with idiopathic dilated cardiomyopathy the results of three assays: (1) isoproterenol-sensitive adenylate cyclase; (2) ligand binding inhibition; (3) enzyme-linked immunoassay (ELISA) of beta-receptor peptides. In 20% of the patients, all three tests gave positive results, while the concordance of the adenylate cyclase assay with either of the other two tests was 65%. ELISA was positive for a beta 1-receptor peptide corresponding to the second extracellular loop, but negative for a beta 2-receptor peptide. The results suggest that autoantibodies in dilated cardiomyopathy sera interact with several components of the beta-receptor-adenylate cyclase, and therefore a combination of methodologic approaches is needed to evaluate the prevalence and consequences of beta-receptor autoimmunity. PMID- 1312762 TI - Plasma lipid and lipoprotein concentrations of men consuming a low-fat, high fiber diet. AB - This study assessed the influence of a low-fat, high-fiber diet on blood lipid concentrations of 42 men with desirable or moderately elevated cholesterol concentrations. A low-fat diet (19% fat, 4% saturated fatty acids, 4.6 g fiber/MJ) was compared with a high-fat diet (41% fat, 15% saturated fatty acids, 2.0 g fiber/MJ) and with subjects' self-selected diets. Substituting the low-fat for the high-fat diet decreased total, low-density-lipoprotein, and high-density lipoprotein cholesterol by 17-20%. Lipid changes between 6 and 10 wk were minor. A reduction in plasma cholesterol of greater than 0.52 mmol/L was achieved with the low-fat diet in 59% of men changing from their self-selected diets and in 79% changing from the high-fat diet. Percent reduction was independent of subjects' cholesterol classification. Results indicate that significant reductions in plasma cholesterol can be achieved by the majority of men committing to a low fat, high-fiber diet. PMID- 1312763 TI - Guar, but not psyllium, increases breath methane and serum acetate concentrations in human subjects. AB - Guar and psyllium are fermented by human fecal bacteria in vitro. To see if they were fermented in vivo, eight subjects were studied over 3 separate days, in random order, while eating a polysaccharide-free diet. Twenty grams guar or psyllium, taken at breakfast, had no effect on breath hydrogen levels over 14 h. Mean breath methane and serum acetate concentrations after guar, 37 +/- 1 ppm and 93 +/- 6 mumol/L, respectively, were significantly greater than after control, 20 +/- 2 ppm (P less than 0.05) and 62 +/- 4 mumol/L (P less than 0.01), and psyllium, 20 +/- 2 ppm (P less than 0.05) and 78 +/- 6 mumol/L (P less than 0.05). Serum acetate increased after guar (area under curve 193 +/- 56 mumol.h/L; P less than 0.02) but decreased after psyllium and control. We conclude that guar is fermented in the human colon, producing rises in breath methane and serum acetate but not hydrogen. Although psyllium had no effect on hydrogen, methane, or acetate, this does not prove that it is not fermented. PMID- 1312764 TI - Colonic fermentation and markers of colorectal-cancer risk. AB - The aim of this study was to determine the effect of soluble fiber on indexes of colon-cancer risk in postpolypectomy and nonpolyp patients. Forty-five postpolypectomy and 49 nonpolyp volunteers completed 2-wk metabolic studies where half of the group received oat-bran supplements and the other half took wheat brain supplements. Colonic biopsies taken before and after the intervention showed no difference in the index of thymidine colonic-crypt-cell labeling, thymidine-labeling pattern, or nuclear aberrations. Nevertheless, fecal pH was significantly reduced by 0.23 +/- 0.07 pH units (P less than 0.002) as an index of increased colonic fermentation on oat bran. This was not associated with increased basal breath hydrogen concentrations; fecal butyrate concentrations were higher on wheat bran. We conclude that soluble fiber as oat brain appears to have no advantage over wheat bran in modifying putative risk factors for colonic cancer. PMID- 1312765 TI - Dietary changes in older Americans, 1977-1987. AB - This study compares dietary practices of persons aged greater than or equal to 65 y surveyed as part of the 1977-78 and 1987-88 Nationwide Food Consumption Surveys. Intakes of high-fat beef and pork, whole milk, and white bread decreased with increases in low-fat beef, pork, poultry and fish, low-fat milk, and whole grain breads. However, consumption of many important sources of calories and fat (high-fat desserts, butter, and margarine) and fiber (fruits, high-fiber cereals, and vegetables) changed little between 1977 and 1987. The food-consumption trends translated into modest changes in overall nutrient intake. Gender differences were small and contradict the prevailing feeling that women are changing their diets more rapidly than are men. The authors suggest that public health messages have focused too heavily on foods to avoid while not giving adequate guidance for how to plan and prepare meals that will enable older Americans to meet the current diet and health recommendations. PMID- 1312766 TI - Phosphate transport by plasma membranes of enterocytes during development: role of 1,25-dihydroxycholecalciferol. AB - The present studies were designed to investigate phosphate transport across the brush border and basolateral membranes of enterocytes and to determine the effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on these processes in suckling and adolescent rats. Vitamin D deficiency was induced in suckling rats by feeding pregnant dams a vitamin D-deficient diet 48 h after insemination; they were then kept in the dark. Vitamin D deficiency in the adolescent rats was induced by feeding the vitamin D-deficient diet to weanling rats for 4 wk. V max values for Na(+)-dependent phosphate uptake in the brush border membranes of vitamin D deficient and 1,25(OH)2D3-injected suckling rats was 0.7 +/- 0.1 and 1.5 +/- 0.2 nmol.mg protein-1.10 s-1 (P less than 0.01), respectively; V max values in adolescent rats were 0.2 +/- 0.05 and 0.36 +/- 0.04 nmol.mg protein-1.10 s-1 (P less than 0.05), respectively. Vmax values for Na(+)-dependent phosphate uptake in basolateral membranes of vitamin D-deficient and 1,25(OH)2D3-treated suckling rats were 0.006 +/- 0.001 and 0.047 +/- 0.006 nmol.mg protein-1.10 s-1 (P less than 0.01). PMID- 1312767 TI - A study of oral etoposide, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small-cell lung cancer. A Mid-Atlantic Oncology Program study. AB - A combination of oral etoposide, infusional cisplatin (24-hr) and infusional 5 fluorouracil (5-day) was used to treat 87 patients with non-small-cell lung cancer in a Phase II trial. Twenty-six patients were Stage IIIB, and 61 patients were Stage IV (new international classification). The regimen was well tolerated, with 49% grade 3 or 4 toxicities of all types. Response rates, partial and complete, were 40%, (95% confidence interval: 30%, 51%) for Stage IV patients and 20% (95% confidence interval: 10%, 32%), in Stage IIIB. An additional 68% of patients in Stage IIIB and 45% of patients in Stage IV achieved stable disease and had a median survival of 8.8 months, similar to that of patients in partial remission. Median survival was 5.6 months (95% confidence interval: 4.4 months, 10.8 months) for Stage IV patients and 11.0 months (95% confidence interval: 8.8 months, 12.4 months), for Stage IIIB. Of interest was the finding of a higher response rate in patients with a shorter duration of symptoms (less than 6 months versus greater than 6 months). PMID- 1312768 TI - Mitomycin C, vindesine, and cisplatin in advanced non-small-cell lung cancer. A phase II study. AB - Between August 1985 and June 1986, 49 previously untreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) were treated with the combination of cisplatin 80 mg/m2 i.v. on day 1, vindesine 3 mg/m2 i.v. on days 1 and 8, and mitomycin-C 8 mg/m2 i.v. on day 1 (MVP), repeating after an interval of 4 weeks, and thereafter every 6 weeks. The median age for all patients was 62 years, with a range of 21 to 77 years. All patients had a performance status of 0, 1, or 2 (ECOG scale) and measurable disease. Histologic types included squamous cell carcinoma (22 patients), adenocarcinoma (22 patients), and large cell carcinoma (6 patients). Forty-eight patients were evaluable for response. Out of 48 patients, one (2%) achieved a complete response and 24 patients (50%) achieved a partial response, resulting in an overall response rate of 52% (95% confidence interval, 38-68%). The response rates were 52% for squamous cell carcinoma, 45% for adenocarcinoma, and 80% for large-cell carcinoma, respectively. The median duration of response was 4.2 months and the median duration of survival for all patients was 10.6 months. The major toxicity was myelosuppression. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 85% and 33%, respectively. One patient died of sepsis associated with leukopenia. Other toxicities were manageable and reversible. In conclusion, the MVP regimen was active and tolerable in patients with advanced NSCLC. Prospective randomized study comparing the MVP regimen with the two-drug combination of vindesine and cisplatin is warranted. PMID- 1312769 TI - Non-small-cell lung cancer (NSCLC): chemotherapy in advanced disease. Our experience in ten years. AB - This is a review of the therapeutic schedules used in our service during the past 10 years for the therapy of advanced non-small-cell lung cancer. During the first years, nonrandomized trials were conducted and several combinations were tested: MACC (methotrexate, doxorubicin, cyclophosphamide, and CCNU), cisplatin etoposide, and cisplatin-vindesine. The results of these trials were invariably discouraging: objective responses hardly reached 30%, while the survival was around 15 months in the best case. On December 1985 a new randomized trial, based on the combination MIP (mytomicin, ifosfamide, cisplatin) was designed; 60.7% of objective responses were achieved, with 9 complete remissions (17.6%) and 22 partial remissions (43.1%). Median survival was 15 months. In order to reduce the toxicity of this combination, carboplatin was substituted for cisplatin. Unfortunately, results were very poor. No complete remission, and only 5 partial responses (20%) were achieved. At the present time, a new randomized trial is being conducted. In it, MIP combination is compared with VIP (vindesine, ifosfamide, cisplatin). Preliminary results have shown no differences between both arms in response, toxicity, or survival. New therapeutic approaches, as neoadjuvant therapy, are being explored. PMID- 1312770 TI - Intra-arterial and intravenous use of 4' epidoxorubicin combined with 5 fluorouracil in primary hepatocellular carcinoma. A randomized comparison. AB - Between October, 1986, and March, 1990, 20 consecutive untreated and noncirrhotic patients with measurable and histologically and/or cytologically confirmed unresectable primary liver cancer were randomly assigned to intravenous (10 patients) or intra-arterial (10 patients) therapy. Patients were treated every 4 weeks with a combination chemotherapy regimen containing 4' epidoxorubicin and 5 fluorouracil. A 3-min bolus injection of 4' epidoxorubicin was followed by 5 fluorouracil given in a 90-min infusion. The dose of 4' epidoxorubicin was escalated: the starting dose was 40 mg/m2, the second dose was 50 mg/m2, and thereafter 60 mg/m2 during subsequent cycles. The dose of 5-fluorouracil was always 800 mg/m2. Objective response rates (20%) were similar in both treatments; two patients had partial responses in the intra-arterially treated group and one complete and one partial response were recorded in the intravenously treated group. The median survival time was 15.2 months for the patients treated intra arterially and 13.8 months for the patients treated intravenously. Toxicity was mainly mild in both groups with less hematopoietic toxicity in the I.A.-treated group. 4' epidoxorubicin combined with 5-fluorouracil given intra-arterially is not superior to the intravenous therapy, but it may diminish systemic toxicity. PMID- 1312771 TI - A serosurvey of pathogens associated with shellfish: prevalence of antibodies to Vibrio species and Norwalk virus in the Chesapeake Bay region. AB - Recent concerns regarding the safety of shellfish consumption have focused on the risk posed by naturally occurring marine bacteria such as Vibrio species and by viruses such as Norwalk and related agents. Despite the widespread environmental presence of Vibrio species in the Chesapeake Bay, the rate of reported infections remains low; there have also been no reports of major Norwalk outbreaks associated with shellfish in this area. As infections with these agents may not always be recognized because of difficulties in making the diagnosis and/or their mild or subclinical presentation, a serosurvey was conducted among healthy volunteers living in the Chesapeake Bay region. Serum and questionnaire data were collected during the fall of 1987 from 267 persons with varying levels of exposure to shellfish: shellfish industry workers, persons attending a local seafood festival, and Seventh-day Adventists (who traditionally abstain from eating shellfish). In comparisons among groups, a significant association could not be demonstrated between shellfish consumption or contact and antibody response to Vibrio cholerae O1 or Norwalk virus. Rates of seropositivity were high for both agents (up to 22% seropositive with a V. cholerae O1 Inaba vibriocidal assay, 14% with an enzyme-linked immunosorbent assay for cholera toxin, and up to 70% seropositive with an enzyme-linked immunosorbent assay for antibodies to Norwalk virus); the basis for these responses in population-based studies remains to be determined. Shellfish industry workers did have a significantly elevated antibody response to the unencapsulated phase variant of Vibrio vulnificus as compared with the other groups studied. Infection with V. vulnificus may be relatively common among persons with high levels of exposure to shellfish. PMID- 1312772 TI - Epidemic poliomyelitis in The Gambia following the control of poliomyelitis as an endemic disease. I. Descriptive findings. AB - An epidemic of type 1 poliomyelitis involving 305 cases occurred in The Gambia (estimated 1986 population, 768,995) from May through November 1986, following a 6-year period when only five cases were reported. Cases were identified by physician reporting during the epidemic and by a national village-to-village search conducted after the epidemic. The national attack rate was 40 cases per 100,000 people. Cases lived in all parts of the country except the capital, Banjul. The peak month of the epidemic was August (139 cases). The highest attack rate by year of age was in 1-year-old children (394 cases per 100,000 persons), and 75% of cases were 3 years of age or less. A vaccination coverage survey showed that 64% (95% confidence interval 60-68) of 1- to 2-year-old children were vaccinated with at least three doses of trivalent oral polio vaccine at the beginning of the epidemic. Fifty-seven cases became paralyzed more than 2 weeks after a national mass campaign in which 95% of children 1-7 years old were reported to have received a dose of trivalent oral polio vaccine. Experience in The Gambia shows that a several-year period of excellent control of endemic poliomyelitis by a vaccination program can be followed by a major epidemic and that a mass vaccination campaign may be only partially successful in ending the epidemic. PMID- 1312773 TI - Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. AB - OBJECTIVE: We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia. STUDY DESIGN: A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis. RESULTS: The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection. CONCLUSION: Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease. PMID- 1312774 TI - Immunofluorescent staining and corneal sensitivity in patients suspected of having herpes simplex keratitis. AB - We examined immunofluorescent staining and corneal sensitivity in 25 control subjects (25 eyes) with normal corneas, six patients (eight eyes) with possible herpes simplex keratitis, and 44 patients (48 eyes) with corneal lesions (recurrent erosion, superficial punctate keratitis, marginal ulcer, and follicular keratoconjunctivitis) in whom herpes simplex keratitis was not suspected. On immunofluorescent staining, all 25 control subjects had negative reactions, all eight eyes suspected of having herpes simplex keratitis had positive reactions, and 11 (23%) of the 48 eyes not suspected of having herpes simplex keratitis had positive reactions; the remaining 37 eyes had negative reactions. Of the 11 eyes not suspected of having herpes simplex keratitis but that had positive reactions on immunofluorescent staining, nine had recurrent erosions and the remaining two eyes had superficial punctate keratitis. Of the eight eyes with possible herpes simplex keratitis, seven (88%) had decreased corneal sensitivity. Of the 11 eyes not suspected of having herpes simplex keratitis but that had positive reactions on immunofluorescent staining, eight (73%) had decreased corneal sensitivity. Of the 37 eyes not suspected of having herpes simplex keratitis that had negative reactions on immunofluorescent staining, 11 (30%) had decreased corneal sensitivity. PMID- 1312775 TI - Hypoxia-induced increased permeability of endothelial monolayers occurs through lowering of cellular cAMP levels. AB - Prolonged exposure to hypoxia, as at high altitude, results in increased vascular permeability that may be ameliorated by administration of glucocorticoids. To understand mechanisms underlying these observations, cultured bovine aortic and pulmonary artery endothelial cells (ECs) were subjected to hypoxia, and changes in monolayer permeability and adenosine 3',5'-cyclic monophosphate (cAMP) levels were assessed. Exposure of both types of cultured ECs to hypoxia (PO2 approximately 14 Torr) led to a time- and dose-dependent increase in monolayer permeability, as measured by diffusion of radiolabeled solutes, which was associated with a progressive decrease in EC cAMP levels from 60 to 15 pmol/mg protein, and a decrease in EC adenylate cyclase activity. The change in endothelial barrier function was prevented by addition of cAMP analogues. Pertussis toxin protected EC monolayers from hypoxia-mediated increase in permeability while maintaining cAMP levels and adenylate cyclase activity. Addition of dexamethasone to EC monolayers before or simultaneously with their incubation under hypoxic conditions blocked the hypoxia-mediated increase in monolayer permeability. Dexamethasone pretreatment also prevented the decline in cAMP and adenylate cyclase levels in oxygen-deprived cultures. These data indicate that hypoxia decreases EC barrier function by lowering adenylate cyclase activity and cellular cAMP levels. They suggest that dexamethasone may exert its protective effect, in part, by preventing the hypoxia-induced decline in adenylate cyclase activity, leading to an increase in cellular cAMP and maintenance of EC barrier function. PMID- 1312776 TI - Juxtaglomerular cells cultured on a reconstituted basement membrane. AB - Circulating renin levels are regulated by release from juxtaglomerular (JG) cells. Here, for the first time, we describe the primary culture of rat juxtaglomerular cells on a reconstituted basement membrane. In addition, primary cultures were transformed with a temperature-sensitive SV40 large T antigen gene to promote the development of a continuous JG cell line. Both primary cultures and transformed JG cells maintain a highly differentiated state and secrete active renin. These preparations now provide a system in which characterization of the cellular mechanisms of regulation of renin synthesis and release is possible. PMID- 1312777 TI - Distribution of actin filament lengths measured by fluorescence microscopy. AB - We analyzed the distribution of actin filament lengths by optical microscopy (OM). OM avoids possible alterations in the size or structure of actin filaments occurring during sample preparation for electron microscopy (EM). Images of F actin labeled with tetramethylrhodamine isothiocyanate (TRITC)-phalloidin were analyzed for both size distribution and flexibility. In the standard buffer [25 mM potassium acetate, 4 mM MgSO4, 25 mM tris(hydroxymethyl)aminomethane acetate, pH 7.5, 20 mM beta-mercaptoethanol] filaments did not aggregate into bundles and remained stable at nanomolar concentrations for at least 1 h. At the same concentration, actin labeled directly with rhodamine (no phalloidin) formed unstable filaments whose average length decreased with time. The number average length of TRITC-phalloidin labeled filaments (Ln) was 4.90 microns, the ratio (rho) of the weight average length to the number average length was 2.06, and the correlation length (1/lambda) was 8.33 microns. These parameters were in good agreement with the values determined by EM for filaments shorter than 8 microns. Passing G-actin through a Sephadex G-150 column before polymerization did not have a significant effect on the distribution of lengths but made filaments more stiff (1/lambda = 12.5 microns). Millimolar concentration of ATP increased the correlation length, and gelsolin had the expected fragmenting effect on filaments. These results show that OM can be used as a fast and reliable method to analyze the distribution and flexibility of actin filaments and suggest that, in spite of extensive manipulation of actin filaments during sample preparation, EM is a valid tool for determination of size parameters of actin filaments. PMID- 1312778 TI - Calcium channels and control of cytosolic calcium in rat and bovine zona glomerulosa cells. AB - Rat and bovine adrenal zona glomerulosa (ZG) cells possess a low-threshold, voltage-dependent Ca2+ current that was characterized using whole cell voltage clamp techniques. Activation of this current is observed at membrane potentials above -80 mV with maximal peak Ca2+ current elicited near -30 mV. Inactivation of the Ca2+ current was half-maximal between -74 and -58 mV, depending on the external Ca2+ concentration and was nearly complete at -40 mV. The voltage dependency of the current indicates that a calcium current could be sustained at membrane potentials between -80 and -40 mV and thereby elevates cytosolic calcium (Cai) levels. Under basal conditions, Cai is stable in single rat ZG cells, whereas more than half of the bovine ZG cells produce repeated Cai transients. These Cai transients, which are blocked by removal of external Ca2+ or addition of Ni2+, are likely due to repetitive electrical activity in bovine ZG cells. Cai responses can be elicited by small increases in external K+ concentration (5-10 mM) in both rat and bovine ZG cells, indicating the opening of low-threshold Ca2+ channels. However, these Cai changes remain robust at high external K+ concentrations (20-40 mM). In experiments combining Cai measurements and whole cell voltage clamp, a steep dependence of Cai on membrane potential was revealed beginning at depolarizing voltages near a holding membrane potential of -80 mV. A maximal increase in Cai occurred near -30 mV (equivalent to an external K+ concentration of 40 mM), a membrane voltage at which sustained current through low-threshold Ca2+ channels should be negligible. These data raise the possibility of additional voltage-dependent pathways for Ca2+ influx. PMID- 1312779 TI - P2 purinergic receptors and cellular calcium metabolism in A 431 human epidermoid carcinoma cells. AB - Stimulation of P2 purinergic receptors on A 431 human epidermoid cells with ATP rapidly mobilized intracellular calcium and increased cytosolic free Ca2+ ([Ca2+]i). Incorporation of 45Ca2+ was also stimulated by ATP at a rate less than that of [Ca2+]i elevation. Among a number of nucleosides, nucleotides, and their analogues examined, ATP, GTP, UTP, ADP, UDP, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), and 5'-adenylylimidodiphosphate (AMP-PNP) increased both [Ca2+]i and 45Ca2+ influx, whereas others did not; these latter two analogues (ATP gamma S and AMP-PNP) blocked the ATP-stimulated 45Ca2+ influx only very slightly, suggesting that they are not prominent antagonists but rather agonists. A high correlation between [Ca2+]i increase and 45Ca2+ influx, in terms of nucleotide specificity, suggests the involvement of [Ca2+]i in influx of 45Ca2+. It appeared that [Ca2+]i elevated by several nucleotides or nucleotide analogues opened a calcium gate, thus allowing the influx of 45Ca2+. P2 purinergic receptors on these cells had such a characteristic that they were rapidly desensitized. These nucleotides or analogues also affected epidermal growth factor (EGF) receptors by inhibiting the EGF binding. The differences of ligand or substrate specificities between P2 purinergic receptors and ecto-nucleotidases indicates that the two components are different molecules involved in different systems. PMID- 1312780 TI - Sarcolemmal Na(+)-K(+)-ATPase activity in congestive heart failure due to myocardial infarction. AB - Because the Na+ pump is considered to modulate the contractile force development by the cardiac muscle and depressed cardiac pump function is the hallmark of congestive heart failure, we characterized the sarcolemmal Na(+)-K(+)-ATPase activity in failing rat hearts after myocardial infarction. For this purpose, the left ventricular coronary artery was ligated, and hearts were examined 4, 8, and 16 wk later; sham-operated animals served as controls. Hemodynamic assessment revealed the presence of abnormal cardiac function at 4, 8, and 16 wk. Although accumulation of ascites in the abdominal cavity was present in experimental animals at 4 wk, other clinical signs of congestive heart failure in experimental rats including lung congestion and cardiac dilatation were evident 8 and 16 wk after induction of myocardial infarction. The depression in Na(+)-K(+)-ATPase activity in purified sarcolemmal membrane from the uninfarcted experimental left ventricle at 8 wk was associated with depressed Vmax without any changes in the affinities for Mg-ATP, Na+, and K+ or the pH optimum for the enzyme. The Kd values of both the high- and low-affinity binding sites for [3H]ouabain, which is believed to interact with Na(+)-K(+)-ATPase, were increased; however, no change in the density of either class of ouabain binding site was evident. The depression of Na(+)-K(+)-ATPase activity in failing hearts at 16 wk of myocardial infarction was not different from that observed at 8 wk but the enzyme activity was not altered at 4 wk of coronary occlusion. These data support the view that depression of Na(+)-K(+)-ATPase activity may serve as an adaptive mechanism during the development of congestive heart failure. PMID- 1312781 TI - Regulation of glucose transport and GLUT1 glucose transporter expression by O2 in muscle cells in culture. AB - The effect of varying cellular oxygenation on L6 muscle cell 2-deoxy-D-glucose transport, glucose utilization, lactate production, and expression of GLUT1 and GLUT4 transport proteins was investigated. Incubation of L6 myotubes in 3% O2 (mimicking a state of hypoxia) elevated glucose uptake by 6.5-fold over 48 h relative to cells incubated in 21% O2 (normoxia). Incubation of L6 cells in hyperoxic conditions (50% O2) significantly depressed glucose uptake by 0.4-fold. These effects were fully reversible. Incubation in 3% O2 also caused lactate accumulation and enhanced glucose consumption from the medium. Hypoxia elevated 2 deoxy-D-glucose transport even when the concentration of glucose in the medium was kept constant, suggesting that glucose deprivation alone was not responsible for increased cellular glucose uptake. Incubation in 3% O2 also elevated 3-O methylglucose uptake but not amino acid uptake. Cycloheximide prevented the hypoxia-induced increase in glucose uptake, indicating that de novo synthesis of glucose transport-related proteins was the major means by which cells increased glucose uptake. The content of GLUT1 glucose transporter was significantly elevated in total membranes of cells incubated in 3% O2 and depressed in membranes from cells incubated in hyperoxic conditions, whereas GLUT4 expression was not affected. These results indicate that hypoxia induces an adaptive response of increasing cellular glucose uptake through elevated expression of GLUT1 in an attempt to maintain supply of glucose for utilization by nonoxidative pathways. PMID- 1312782 TI - Regulation of calcium current by voltage and cytoplasmic calcium in canine gastric smooth muscle. AB - The regulation of Ca2+ current by intracellular Ca2+ was studied in isolated myocytes from the circular layer of canine gastric antrum. Ca2+ current was measured with the whole cell patch-clamp technique, and changes in cytoplasmic Ca2+ ([Ca2+]i) were simultaneously measured with indo-1 fluorescence. Ca2+ currents were activated by depolarization and inactivated despite maintained depolarization. Ca2+ current inactivation was fit with a double exponential function. Using Ba2+ or Na+ as charge carriers removed the fast component of inactivation, whereas enhanced intracellular buffering of Ca2+ did not remove the fast component. Ca2+ currents were associated with a rise in [Ca2+]i. The decrease in [Ca2+]i following repolarization was exponential, and during the relaxation of [Ca2+]i, Ca2+ current was inactivated. The inward current recovered with a similar time course as the decrease in [Ca2+]i, suggesting that [Ca2+]i regulates the basal availability of Ca2+ channels. These data support the hypothesis that, although [Ca2+]i may influence the resting level of inactivation, it is the "submembrane" compartment of [Ca2+]i that regulates the development of inactivation. PMID- 1312783 TI - Phylogenetic conservation of isoform-specific regions within alpha-subunit of Na(+)-K(+)-ATPase. AB - Site-directed polyclonal antibodies were generated against four oligopeptides derived from the rat alpha-isoforms of Na(+)-K(+)-adenosinetriphosphatase (i.e., Na(+)-K+ pump) and were used to assess the phylogenetic conservation of the target regions. The first antibody was directed against a region near the phosphorylation site that is conserved among alpha-subunits from numerous species. The remaining antibodies were specific for the isoforms of alpha and recognized a region near the fluorescein isothiocyanate-reactive lysine of the adenine binding site. Immunoblots of protein from a number of species probed with these antibodies revealed dramatic differences in the conservation of the target sequences. The region derived from alpha 1 was found in four of the six mammals screened. In contrast, the analogous region derived from alpha 2 was found in all the screened mammals. Most conserved was the region derived from alpha 3, which was found in all the screened mammals as well as in chickens, catfish, dogfish, and sea slugs. Conservation of the region from alpha 3 suggests functional significance and implies that strong selective pressures have discouraged mutational change. Results from the immunoblots further suggest that isoforms are present in all vertebrates. PMID- 1312784 TI - Regulated endocytosis in a chloride secretory epithelial cell line. AB - The colonic epithelial cell line T84 has been shown to be a good model to investigate the regulation of Cl- secretion by the adenosine 3',5'-cyclic monophosphate (cAMP)-mediated second messenger cascade. Regulated exocytic insertion and endocytic retrieval of transport proteins, or proteins that regulate transport proteins, is one mechanism proposed to regulate plasma membrane solute permeabilities. The aims of our studies were to characterize endocytic processes in T84 cells and to investigate their regulation by known activators of Cl- secretion that are mediated by the cAMP second messenger cascade. Forskolin, an activator of adenylate cyclase, caused a marked inhibition of endocytic uptake of the fluid-phase marker horseradish peroxidase (HRP) and the adsorptive marker wheat germ agglutinin conjugated to HRP. Similar inhibition was obtained with vasoactive intestinal peptide, a secretagogue whose receptor is coupled to adenylate cyclase, and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, a membrane-permeable cAMP analogue. 1,9-Dideoxy-forskolin, a forskolin analogue that fails to activate adenylate cyclase, was without effect on endocytosis. Our data show that the net rate of endocytosis, as measured by fluid-phase uptake, is decreased by a cAMP-mediated mechanism. Because the number of Cl- channels or associated regulatory proteins in the plasma membrane reflects a balance between their exocytic insertion and endocytic retrieval, we propose that the cAMP-mediated decrease in endocytosis could contribute to the concomitant increase in plasma membrane Cl- permeability. PMID- 1312785 TI - Recovery from exercise-induced desaturation in the quadriceps muscles of elite competitive rowers. AB - A simple muscle tissue spectrophotometer is adapted to measure the recovery time (TR) for hemoglobin/myoglobin (Hb/Mb) desaturation in the capillary bed of exercising muscle, termed a deoxygenation meter. The use of the instrument for measuring the extent of deoxygenation is presented, but the use of TR avoids difficulties of quantifying Hb/Mb saturation changes. The TR reflects the balance of oxygen delivery and oxygen demand in the localized muscles of the quadriceps following work near maximum voluntary contraction (MVC) in elite male and female rowers (a total of 22) on two occasions, 1 yr apart. TR ranged from 10 to 80 s and was interpreted as a measure of the time for repayment of oxygen and energy deficits accumulated during intense exercise by tissue respiration under ADP control. The Hb/Mb resaturation times provide a noninvasive localized indication of the degree of O2 delivery stress as evoked by rowing ergometry and may provide directions for localized muscle power output improvement for particular individuals in rowing competitions. PMID- 1312786 TI - Effects of D-beta-hydroxybutyrate and long- and medium-chain triglycerides on leucine metabolism in humans. AB - Ketone bodies and/or fatty acids might play a protein-sparing role during prolonged fasting or parenteral nutrition. To assess this problem, we studied whole body leucine metabolism, using L-[1-13C]leucine in normal postabsorptive volunteers who received either long-chain triglycerides (LCT, 0.15 g.kg-1.h-1, 6 subjects), a 50-50 mixture of medium-chain triglycerides (MCT) and LCT (0.15 g.kg 1.h-1, 6 subjects), D-beta-hydroxybutyrate (540 mumol.kg-1.h-1, 6 subjects), or saline (4 subjects). Leucine concentration decreased only with MCT-LCT. Leucine flux decreased by 10-20% from basal in all groups. Leucine oxidation, which was corrected for the contribution to 13CO2 of the 13C natural abundance of the infused substrates, decreased during LCT infusion (0.31 +/- 0.02 to 0.24 +/- 0.01 mumol.kg-1.min-1, P less than 0.01), but was unaffected by MCT-LCT (despite plasma free fatty acid levels similar to those obtained with LCT), D-beta hydroxybutyrate, or saline infusion. Therefore, 1) the effect of fatty acids on amino acid oxidation is not mediated by ketone bodies, 2) it depends on the fatty acid chain length, 3) long-chain fatty acids but not medium-chain fatty acids could play a protein-sparing role during parenteral nutrition. PMID- 1312787 TI - Upregulation of D-myo-inositol transport in diabetic rat glomerular cells. AB - In the streptozotocin (STZ)-treated diabetic rat, reduced glomerular arteriolar resistance leads to raised intraglomerular pressure. Because vasoconstrictor hormones, such as angiotensin II, stimulate arteriolar smooth muscle and mesangial cell contraction via the D-myo-inositol (MI)-dependent transmembrane signaling pathway, in diabetes extracellular D-glucose may inhibit MI transport causing MI depletion, reduced signaling, and hypocontractility. Therefore we studied the regulation of Na-dependent MI transport in the intact cells (mesangial and endothelial) of isolated glomeruli from STZ rats after 2 wk of diabetes, with and without insulin, compared with controls. Specific [3H]MI uptake per milligram glomerular protein (10-150 min, 37 degrees C) was observed in the presence of 0, 5.5, and 30 mM D-glucose using L-[14C]glucose as a marker of nonspecific uptake. D-Glucose competitively inhibited Na-dependent MI transport (maximum velocity) into diabetic and normal glomerular cells. At 5.5 mM D-glucose, MI uptake by diabetic non-insulin-treated glomeruli was increased to 191 +/- 14% (SE) above normal glomeruli. Insulin treatment resulted in less upregulation (116 +/- 11%) of normal MI transport. High glucose concentration did not alter the rate of [3H]MI efflux from preloaded glomerular cells. To determine whether diabetes alters available substrate for transmembrane signaling, after incubation for 120 min, the incorporation of [3H]MI into cellular membrane phosphoinositides and soluble D-myo-inositol phosphates of isolated diabetic and control glomerular cells was compared. Diabetic glomerular cells displayed a significant increase (P less than 0.005) in [3H]MI incorporation into these fractions compared with controls. PMID- 1312788 TI - Role of brain kallikrein-kinin system in regulation of adrenocorticotropin release. AB - We evaluated whether the brain kallikrein-kinin system plays a role in the regulation of adrenocorticotropin (ACTH) release in rats. Intracerebroventricular (icv) injection of bradykinin (0.24 nmol) increased plasma immunoreactive ACTH (irACTH) levels (from 93 +/- 4 to 200 +/- 12 pg/ml, P less than 0.01). This effect was prevented by icv kinin antagonist at 15.4 nmol/h (from 98 +/- 5 to 108 +/- 6 pg/ml; not significant). The antagonist did not alter the increase in plasma irACTH levels induced by icv corticotropin-releasing factor (CRF), arginine vasopressin, or prostaglandin E2. Melittin (7 nmol/h icv) increased plasma irACTH from 95 +/- 4 to 268 +/- 7 pg/ml (P less than 0.01). This effect was prevented by icv kinin antagonist (15.4 nmol/h), kallikrein antibodies (13 pmol/h), or indomethacin (0.28 mmol/h). ACTH response to melittin was not altered by antagonists of CRF or vasopressin. Intra-arterial injection of insulin (0.3 IU/kg body wt) reduced plasma glucose levels to a similar extent in rats given icv kinin antagonist or vehicle; the ACTH response to insulin-induced hypoglycemia was slightly less in rats given kinin antagonist than in those given vehicle (55 +/- 5 vs. 86 +/- 4 pg/ml, P less than 0.05). The brain kallikrein kinin system may play a role in the regulation of ACTH secretion in stimulated conditions. PMID- 1312789 TI - ACTH and cortisol responses to sequential CRF injections in fetal sheep. AB - To determine whether an initial ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to a second injection and to establish whether the effect changes throughout gestation, we studied chronically cannulated fetal lambs of 103-113 and 133-137 days gestation. Experimental groups underwent an injection (500 ng/kg iv) of oCRF, arterial blood sampling for 6 h, then a similar oCRF injection followed by sampling. In control studies, vehicle was the initial injection. After the first oCRF injection, plasma cortisol levels went from 1.7 +/- 0.4 to 9.5 +/- 5.2 (SE) ng/ml ("immature") and from 22.3 +/- 4.9 to 52.5 +/- 5.8 ng/ml ("mature"), remaining elevated for 6 h. In immature fetuses, the first oCRF injection did not alter the ACTH response to a second injection. Cortisol increases were reduced. In mature animals, ACTH and cortisol response to oCRF were eliminated by prior oCRF. Thus a large increase in cortisol after oCRF in mature fetuses is associated with inhibition of the ACTH response to a second oCRF injection, whereas in immature animals a small increase in cortisol after the first oCRF injection is not. PMID- 1312790 TI - ACTH and cortisol responses to hypotension in fetal sheep after a prior CRF injection. AB - To determine whether an ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to hypotension and whether the effect of any interactions between these stimuli changes across gestation, we studied chronically cannulated fetal lambs of 103-113 ("immature") and 133-139 days gestation ("mature"). Experimental groups received 500 ng/kg oCRF injections and 6 h later had arterial pressure reduced 20% for 10 min with nitroprusside. Blood samples were obtained before and after each manipulation. Controls received vehicle instead of oCRF. The oCRF increased plasma cortisol levels from 2.1 +/- 0.4 to 14.2 +/- 4.7 (SE) ng/ml in immature and 44.9 +/- 2.2 to 102.8 +/- 15 ng/ml in mature animals. In mature fetuses the oCRF did not alter plasma ACTH and cortisol increases due to hypotension. In immature animals ACTH increases were normal but cortisol increases were eliminated. This suggests that the CRF caused maximal stimulation of the adrenal gland. In older fetuses, it appears that the action of ACTH-releasing factors, secreted in response to arterial hypotension, can overcome the negative feedback effects of elevations in endogenous cortisol. PMID- 1312791 TI - Cl- fluxes related to fluid secretion by the rat parotid: involvement of Cl(-) HCO3- exchange. AB - Muscarinic-induced 36Cl- and 86Rb+ (K+ substitute) fluxes were studied in rat parotid acini. Stimulation resulted in a rapid [half time (t1/2) less than 30 s] decrease in both Cl- and Rb+ content (approximately 50 and 30%, respectively) followed by a slower partial recovery (t1/2 approximately 3-4 min) to approximately 80% of resting levels for both ions. Cl- loss was inhibited by the venom of Leiurus quinquestriatus, which contains the maxi-K+ channel blocker charybdotoxin. Cl- recovery was blunted in the presence of bumetanide, an inhibitor of Na(+)-K(+)-Cl- cotransport, or on HCO3- removal and was completely blocked in the presence of bumetanide and 4,4' diisothiocyanostilbene-2,2' disulfonic acid (DIDS), an inhibitor of Cl(-)-HCO3- exchange. In HCO3(-) containing medium a rapid (t1/2 less than 1 min), DIDS-inhibitable cytoplasmic alkalinization (approximately 0.4 pH unit) was observed in acini switched to a Cl(-)-free solution. This alkalinization was not seen in HCO3(-)-free medium but persisted in the absence of Na+, consistent with the presence of a potent Na(+) independent Cl(-)-HCO3- exchanger. Kinetic studies indicated that the half maximal effect of this exchanger for extracellular Cl- was approximately 18 mM. These results are consistent with the hypothesis that secretagogue-induced KCl loss by salivary acinar cells occurs via electrically coupled K+ and Cl- channels. In addition, they provide strong evidence that Cl- entry into, and thus fluid secretion by, these cells is mediated by both Cl(-)-HCO3- exchange and Na(+)-K(+)-Cl- cotransport. PMID- 1312792 TI - Effects of hypoxia on function and morphology of in vitro frog gastric mucosa. AB - The effects of gaseous hypoxia and reoxygenation on oxynticopeptic (OPC) and surface mucous cells (SMC) were examined in in vitro bullfrog gastric fundic mucosae mounted in Ussing chambers. Forskolin-stimulated H+ secretion, transmucosal potential difference (PD), and electrical resistance (R) were monitored in tissues incubated in HCO3(-)-free or HCO3(-)-containing buffer. At serosal pH (pHs) 7.2, 1 h of hypoxia with 100% N2 resulted in a decrease in PD, increase in R, and complete inhibition of H+ secretion. After 30 min of hypoxia, the morphology of OPC changed from the secretory to the nonsecretory state without recognizable cytopathology. Destructive changes in OPC increased progressively at pHs 7.2 as the hypoxic period was prolonged from 4 to 24 h. After 4 h of reoxygenation following 12-24 h of hypoxia, OPC remained necrotic and H+ secretion showed no recovery, whereas in some areas where SMC were exfoliated adjacent SMC showed epithelial restitution. The recovery of H+ secretion and PD during 2 h of reoxygenation after 4 h of hypoxia at pHs 6.0 and 6.8 was less than that at 7.2 and 8.0 and was greater in the presence of serosal HCO3- than its absence at pHs 7.2. These results suggest that, in in vitro frog gastric mucosa, 1) OPC are more vulnerable to hypoxia than SMC, 2) basolateral acidosis exaggerates hypoxic injury of OPC, and 3) serosal HCO3- protects OPC from hypoxic injury. PMID- 1312793 TI - Characterization of opioid receptors on smooth muscle cells from guinea pig stomach. AB - On the basis of opioid-stimulated contraction of dispersed gastric smooth muscle cells it has been suggested that these cells possess opioid receptors of three subtypes: kappa (kappa), mu (mu), and delta (delta). We have used selective peptidase-resistant radioligands, agonists and antagonists, to examine receptor subtypes on dispersed gastric smooth muscle cells from guinea pigs prepared by collagenase digestion. The kappa-agonist U-50488H, the mu-agonist [D-Ala2,N-Me Phe4,Gly5-ol]enkephalin (DAGO), and the delta-agonist [D-Pen2,Pen5]enkephalin (DPDPE) each caused muscle contraction. The concentrations required to caused half-maximal contraction were U50488H (6 pM) greater than DAGO (13 pM) greater than DPDPE (6 nM). The abilities of these agonists to inhibit binding of [3H]U 69593 (kappa-preferring) by 50% were U50488H (43 nM) greater than DAGO (43 microM) greater than DPDPE (200 microM). Their abilities to inhibit binding of [3H]naloxone (mu-preferring) by 50% were DAGO (0.2 microM) greater than U50488H (10 microM) greater than DPDPE (greater than 100 microM). No binding could be detected with the delta-selective ligand [3H]DPDPE. The kappa-preferring antagonist Mr2266 (10 nM) preferentially inhibited contraction stimulated by the kappa-agonist U50488H, and naltrexone (10 nM) (mu-selective antagonist) preferentially inhibited contraction stimulated by the mu-agonist DAGO. ICI 174864 (200 microM; delta-selective antagonist) had no effect on contraction stimulated by mu-, kappa-, or delta-agonists. Contraction stimulated by the delta agonist DPDPE was inhibited by both kappa- and mu-receptor antagonists. Studies on the effect of the antagonists on binding of [3H]naloxone and [3H]U69593 also provided evidence for kappa- and mu-sites but nor for delta-sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312794 TI - Neurotensin and neuromedin N stimulate mucin output from human goblet cells (Cl.16E) via neurotensin receptors. AB - The stably differentiated human intestinal goblet cell line Cl.16E was used to study the effects of two structurally related regulatory peptides, neurotensin (NT) and neuromedin N (NN), on mucus secretion. NT and NN stimulated rapid release of mucins from filter-grown Cl.16E cells, this effect being dose related with a mean effective dose of 36 nM for NT and 422 nM for NN. The order of potency of NT, three NT fragments corresponding to the NH2-terminal part [NT-(1 11)] or to the COOH-terminal part [NT-(8-13) and NT-(9-13)], and NN in promoting mucin release and in inhibiting 125I-labeled NT binding to Cl.16E cell membranes was identical with NT greater than or equal to NT-(8-13) greater than NN greater than NT-(9-13) much greater than NT-(1-11) supporting the hypothesis that NT and NN stimulate mucin output through interaction with a common NT-preferring receptor. Scatchard analysis of equilibrium binding data showed one population of NT binding sites in Cl.16E cell membranes with the following characteristics: binding capacity (Bmax) was 141 fmol/mg of protein and dissociation constant (Kd) was 1.00 nM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312795 TI - Action of alpha 2A-adrenergic receptors in circular smooth muscle of canine proximal colon. AB - Addition of the alpha 2-adrenergic receptor agonist clonidine (1 microM) to tetrodotoxin-treated strips of canine colonic circular smooth muscle resulted in a significant increase in contractile force that was blocked by addition of the alpha 2-antagonist yohimbine (0.1 microM). The alpha 2-receptor antagonist radioligand [3H]rauwolsine bound rapidly and reversibly to a single class of saturable sites (Bmax, 38.4 +/- 6.2 fmol/mg protein) in colonic circular smooth muscle membranes with an affinity (KD = 5.1 +/- 0.9 nM) characteristic of alpha 2 adrenergic receptors in smooth muscle. Studies in cells freshly isolated from circular muscle of canine proximal colon verified the smooth muscle origin of these receptors. Rank order of potency of alpha 2-adrenergic receptor antagonists in competition for [3H]rauwolsine binding was yohimbine greater than oxymetazoline much greater than prazosin. Affinity of alpha 2-receptors for yohimbine was indistinguishable from that of its optical isomer, rauwolsine, in both competition studies (KI = 3.4 nM) and in saturation-binding experiments employing [3H]yohimbine directly (KD = 4.2 nM). The alpha-receptor agonist epinephrine, in competition studies employing [3H]rauwolsine, revealed high affinity binding sites that were converted to low-affinity binding sites for agonist by addition of 100 microM GTP gamma S. Addition of the alpha 2 more selective agonist clonidine (100 microM) resulted in inhibition of adenylate cyclase activity that was abolished by pretreatment of tissue strips with pertussis toxin suggesting coupling of the alpha 2-receptor in colon to adenylate cyclase via the GTP-binding protein Gi. Our data demonstrate a physiological role for adenylate cyclase-coupled receptors of the alpha 2A-subtype in canine colon circular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312796 TI - Hormonal regulation of calcium current in freshly isolated airway smooth muscle cells. AB - Single freshly isolated smooth muscle cells of adult bovine trachea were voltage clamped, and the calcium inward current was separated from K+ currents by blocking the large outward currents with intra- and extracellular Cs+ and extracellular tetraethylammonium chloride. Isoproterenol stimulated peak calcium current (ICa) in a dose-dependent manner through the beta-adrenergic receptor. The isoproterenol effect was not mediated or caused by the stimulation of a K+ or Na+ current, a decrease in the intracellular concentrations of Ca2+ or H+, the stimulation of the Na(+)-H+ or the Na(+)-Ca2+ exchanger. Neither basal nor isoproterenol-stimulated ICa was affected by internal dialysis of the cell with adenosine 3',5'-cyclic monophosphate (cAMP), cAMP analogues, or the catalytic subunit of cAMP-kinase. Internal dialysis of the cells with guanosine 5'-O-(2 thiodiphosphate) (GDP beta S) blocked the stimulation of isoproterenol whereas dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) induced an isoproterenol-like maximal increase of ICa. These results show that the beta adrenergic receptor stimulates the L-type calcium current of isolated tracheal smooth muscle cells independent of cAMP and cAMP-kinase through a GTP/GDP regulated protein. PMID- 1312797 TI - The use of oral mexiletine for the treatment of pain after peripheral nerve injury. AB - Neuropathic pain is often a difficult condition to treat. Clinical and laboratory studies using intravenously administered local anesthetics or antiarrhythmic agents support the use of these drugs for the treatment of neuropathic pain. The availability of the oral antiarrhythmic medication, mexiletine, has made it possible to study the effects of an orally administered medication on chronic neuropathic pain. The study used a double-blind placebo-controlled design to examine 11 subjects in whom treatment with conventional pain medications had been unsuccessful. Subjects had a history of peripheral nerve injury or dysfunction, and all complained of symptoms consistent with neuropathic pain. After baseline pain measurements, mexiletine or placebo was given in gradually increasing doses to a maximum daily dose of 750 mg mexiletine. After 1 month at steady state, the subject received the alternative medication. Mexiletine was found to produce a statistically significant reduction in reported pain when compared to baseline or placebo. Pain scores were rated on a scale from 0 (no pain) to 10 (unbearable pain). Median pain scores prior to mexiletine were 7, after placebo treatment 7, and while receiving mexiletine (750 mg/day) 4. Side effects were mild and well tolerated. Mexiletine may be effective in reducing neuropathic pain for patients in whom alternative pain medications have been unsatisfactory. PMID- 1312798 TI - Halothane effects on human malignant hyperthermia skeletal muscle single calcium release channels in planar lipid bilayers. AB - Malignant hyperthermia (MH) may be life-threatening when genetically predisposed individuals are administered triggering anesthetic agents that are believed to produce intracellular calcium release. To test this theory, the effects of halothane on normal and MH human skeletal muscle calcium-release channels were studied. Single calcium-release channels were incorporated from isolated sarcoplasmic reticulum membrane vesicles into a planar lipid bilayer, and halothane effects on the conductance and gating properties were measured by electrophysiologic techniques. Among the subjects studied, seven were MH susceptible, and 13 channels were recorded from this group. Five subjects were negative for MH, and 10 channels were recorded from this group. Among the 13 channels recorded from the MH group, 7 were affected by halothane, which increased the probability of the channel to change from the inactive, closed state to an open state. This effect of halothane to increase open-state probability was associated with an overall increase in channel conductance. Thus, halothane affected the activation/inactivation process of the halothane-sensitive calcium-release channel from MH muscle as well as the gating properties of the MH calcium-release channel, as evidenced by the increased conductance. In 6 of the 13 channels recorded from MH muscle, halothane (2.2-17.6 microM) was without effect on these properties of the channel. Halothane (2.2-17.6 microM or 0.0057 0.0456 vol%) also had no measurable effect on the 10 channels from the negatively diagnosed subjects. Results of this study support a defect in the ryanodine sensitive calcium-release channel from MH human muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312799 TI - [Prevention of thromboembolism in digestive and abdominal surgery. New heparins]. PMID- 1312800 TI - Effects of overproduction of superoxide dismutases in Escherichia coli on inhibition of growth and on induction of glucose-6-phosphate dehydrogenase by paraquat. AB - Stationary phase inocula were more susceptible to the growth inhibitory effect of paraquat than were log phase inocula and this difference was exacerbated in strains overproducing superoxide dismutases (SOD). Glucose-6-phosphate dehydrogenase (G-6-PD), a member of the soxR regulon, was induced by paraquat promptly in the case of log phase cells; but only after a lag in stationary phase cells and this difference was also exaggerated in strains overproducing SOD. The negative consequences of overproduction of SOD on the adaptation of stationary phase cells to paraquat may be attributed to competition for cellular resources with an attendant delay in biosynthesis of other components of soxR. Since overproduction of SOD did not prevent log phase cells from inducing G-6-PD in response to paraquat, it appears likely that soxR can respond to aspects of redox status other than O2-. This conclusion is in accord with data which is already in the literature. PMID- 1312801 TI - Effects of adenosine administration on the function and membrane composition of liver mitochondria in carbon tetrachloride-induced cirrhosis. AB - The effect of chronic carbon tetrachloride (CCl4) administration on liver mitochondria function and the protective action of adenosine on CCl4-induced damage were assessed in rats made cirrhotic by long-term exposure to the hepatotoxin (8 weeks). The CCl4 treatment decreased the ADP-stimulated oxygen consumption, respiratory control, and ADP/O values, mainly for substrates oxidation of site I, in isolated mitochondria. This impaired mitochondrial capacity for substrate oxidation and ATP synthesis was accompanied by an important diminution (approximately 30 mV) of membrane electrical potential. Disturbances of the mitochondrial membrane, induced by CCl4 treatment, were also evidenced as increased mitochondria swelling and altered oscillatory states of mitochondrial volume, both energy-linked processes. The deleterious effects of CCl4 on mitochondrial function were also reflected as a deficient activity of the malate-aspartate shuttle that correlated with abnormal distribution of cholesterol and phospholipids in membranes obtained from submitochondrial particles. Adenosine treatment of CCl4-poisoned rats partially prevented the alterations in mitochondria membrane composition and prevented, almost completely, the impairment of mitochondria function induced by CCl4. Although the nature of the protective action of adenosine on CCl4-induced mitochondria injury remains to be elucidated, such action at this level might play an important role in the partial prevention of liver damage induced by the CCl4. PMID- 1312802 TI - Effect of lipophilic chelators on oxyradical-induced DNA strand breaks in human granulocytes: paradoxical effect of 1,10-phenanthroline. AB - Strand breaks can be produced in the DNA of intact granulocytes by a flux of oxyradicals (O2- and H2O2) generated by tetradecanoylphorbol acetate (TPA) or by a flux of H2O2 generated by glucose oxidase. The mechanism by which such breaks are induced is still uncertain. Lipophilic chelators such as dipyridyl and 1,10 phenanthroline (OP) strongly inhibit strand breaks induced by H2O2, presumably because of their ability to chelate intracellular iron. We now report that dipyridyl also partially inhibits strand breaks in TPA-stimulated granulocytes while a "copper-specific" lipophilic chelator, neocuproine, has no effect. As opposed to these effects, OP increases the number of strand breaks in TPA stimulated granulocytes. Superoxide dismutase (SOD) (but not catalase) partially blocks this increase. Both the cell-impermeable chelator, EDTA, and neocuproine strongly block the increase also. In fact, in the presence of EDTA, OP behaves like dipyridyl and inhibits strand breaks. Preformed OP2-copper(II) complex causes DNA breaks in TPA-stimulated granulocytes. The paradoxical effect of OP may be explained by assuming that OP may form two different metal complexes, a DNA-damaging complex with copper or an inhibitory complex with iron. If copper(II) and O2- are present, the first complex may form and the net effect may be an increase in strand breaks. If the formation of this complex is prevented by SOD, EDTA, or neocuproine, then OP may complex iron and the net effect may be (like dipyridyl) an inhibition of strand breaks. The source of the copper responsible for the formation of OP2-copper complex is unknown. PMID- 1312804 TI - Purification of Chlamydomonas 28-kDa ubiquitinated protein and its identification as ubiquitinated histone H2B. AB - One of the most predominantly ubiquitinated protein species in Chlamydomonas, of which the apparent molecular mass in SDS-PAGE was 28 kDa, was found to exist abundantly in nuclei. The 28-kDa ubiquitinated protein was purified to homogeneity from the isolated nuclei of Chlamydomonas, and its partial amino acid sequence was determined. The N-terminal peptide sequence was identical with that of ubiquitin. Sequences homologous to those Chlamydomonas ubiquitin [corrected] and wheat histone H2B, and paired sequences of both of them were found in arginylendopeptidase-digested or protease V8-digested polypeptide fragments of the 28-kDa ubiquitinated protein. Based on these results, it was concluded that Chlamydomonas 28-kDa ubiquitinated protein is monoubiquitinated histone H2B. PMID- 1312803 TI - Electrostatic modulation of the kinetics of electron transfer from cytochrome c to cobalt phenanthroline by binding to lipid bilayers: effects of ionic strength and extent of incorporation of various negatively charged lipids. AB - The effect of electrostatically binding ferrous cytochrome c to anionic liposomes, composed of dimyristoyl phosphatidylglycerol (DMPG-), dioleoyl phosphatidyl-glycerol (DOPG-), or cardiolipin (CL2-) mixed with varying amounts of egg phosphatidylcholine (PC), on the kinetics of cytochrome oxidation by the positively charged cobalt phenanthroline ion has been measured using stopped-flow spectrophotometry. The rate of electron transfer is enhanced as much as 3000-fold by increasing the number of negatively charged binding sites on the liposome surface, and by as much as 1000-fold by decreasing the ionic strength of the buffer. The sigmoidal shape of the curve of rate constant vs mole percent anionic lipid is consistent with a positively cooperative effect of the negative surface charge. The rate stimulation is greater for DOPG(-)- and CL2(-)-containing liposomes than for DMPG- vesicles; this is most likely due to structural differences in the respective liposomes. The results do not provide any support for a role of structural changes in the bound cytochrome in influencing oxidation kinetics, a possibility suggested by recent spectroscopic measurements, although relatively small conformational effects cannot be completely ruled out. PMID- 1312806 TI - A two-step mechanism of fluoride inhibition of rat liver inorganic pyrophosphatase. AB - Product formation curves for inorganic pyrophosphatase-catalyzed hydrolysis of pyrophosphate in the presence of fluoride were analyzed in order to get insight into the mechanism of its inhibitory action on this enzyme. The enzymatic reaction was monitored with a phosphate analyzer operating on the time scale of seconds. Inhibition patterns were virtually identical for cytosolic and mitochondrial pyrophosphatases. The effect of fluoride was biphasic: it caused a rapid (t 1/2 less than 1 s) decrease in the initial velocity of the reaction followed by slow (t 1/2 greater than or equal to 4 s) inactivation of the enzyme during catalysis. The slow phase resulted in trapping intact substrate at the active site, and the resulting complex could be isolated by gel filtration. Pyrophosphatase remained active when incubated with fluoride in the absence of pyrophosphate or in the presence of its bisphosphonate analogs, which are bound to but not hydrolyzed by this enzyme. These features of the inhibition are consistent with the mechanism in which rapid binding of the inhibitor to the enzyme.substrate complex is followed by its slow isomerization. Kinetic parameters obtained in this work indicate that appreciable inactivation of pyrophosphatase can occur at fluoride concentrations found in human plasma. This effect may therefore be one of the major factors contributing to fluoride toxicity. PMID- 1312805 TI - Detergents affect insulin binding, tyrosine kinase activity and oligomeric structure of partially purified insulin receptors. AB - Insulin receptor activities, i.e., insulin binding and tyrosine kinase activation depend on the lipid environment of the receptor. As detergent may disrupt or interfere with this environment, we investigated the effect of various common detergents on insulin receptor properties. Experiments were carried out (i) on solubilized and partially purified insulin receptor and (ii) on the receptor reconstituted into phosphatidylcholine vesicles. The detergents tested, Triton X 100, octyl-beta-D-glucopyranoside, octyl-beta-D-thioglucopyranoside, 3[(3 cholamidopropyl)dimethylammonio]propanesulfonic acid (Chaps), and Na deoxycholate affected the insulin receptor properties differently when compared with the control receptor in the absence of detergent. On the partially purified insulin receptor, Na deoxycholate inhibited both insulin receptor activities; octyl-beta D-glucopyranoside and octyl-beta-D-thioglucopyranoside decreased insulin binding and kinase activation as their concentration increased, particularly above their respective critical micellar concentration (CMC). Triton X-100 was the only detergent which allowed an increase of insulin binding and kinase activation throughout the whole range of concentrations assayed. Reconstitution of the receptor into phosphatidylcholine vesicles protected the receptor from the direct effects of the detergents, for both the stimulation observed with Triton X-100 and the inhibition produced by the other detergents. In order to determine the effect of detergents on the oligomeric forms of the soluble insulin receptor, we investigated a new rapid sucrose gradient centrifugation technique. Insulin receptors were detected on the gradient by 125I insulin binding. For low concentrations of detergent, i.e., near the CMC, octylglucoside, Chaps, and Triton X-100 favored the (alpha 2 beta 2)2 oligomeric form of the receptor. Higher concentrations of Triton X-100 did not modify the polymeric state of the receptor. In contrast, octylglucoside and Chaps induced an increase in the sedimentation coefficient of the receptor which appeared as (alpha 2 beta 2)3 and (alpha 2 beta 2)4 forms. These alterations in the oligomerization status of the insulin receptor may explain the deleterious effects observed with both Chaps and octylglucoside at higher concentrations. PMID- 1312807 TI - Expression and turnover of acylphosphatase (muscular isoenzyme) in L6 myoblasts during myogenesis. AB - Acylphosphatase (muscular isoenzyme) levels have been measured in L6J1 myoblasts either proliferating or differentiating into myotubes. Results indicated that the increase in enzyme levels during differentiation is very similar to that of creatine kinase, a specific muscular enzyme. The half-lives of acylphosphatase in myoblasts and myotubes were also determined; t1/2 values of 3 h 30 min (myoblasts), and 2 h 18 min (myotubes) were found. These results indicate that acylphosphatase could be considered a short-lived muscle-specific protein and that its increase in myotubes must be accompanied by an activation of its breakdown. PMID- 1312808 TI - Transferrin: a potential source of iron for oxygen free radical-mediated endothelial cell injury. AB - The ability of transferrin to potentiate oxygen free radical-mediated endothelial cell injury was assessed. 51Cr-labeled endothelial cells derived from rat pulmonary arteries (RPAECs) were incubated with hydrogen peroxide (H2O2) in the presence and absence of holosaturated human transferrin, and the effect of transferrin on H2O2-mediated endothelial cell toxicity was determined. Addition of holosaturated transferrin potentiated H2O2-mediated RPAEC cytotoxicity at concentrations of H2O2 greater than 10 microM, suggesting that transferrin may provide a source of iron for free radical-mediated endothelial cell injury. Free radical-mediated injury is dependent on non-protein-bound iron. The ability of RPAECs to facilitate the release of iron from transferrin was assessed. We determined that RPAECs facilitate the release of transferrin-derived iron by reduction of transferrin-bound ferric iron (Fe3+) to ferrous iron (Fe2+). The reduction and release of transferrin-derived Fe2+ were inhibited by apotransferrin and chloroquine, indicating a dependence on receptor-specific binding of transferrin to the RPAEC cell surface, with subsequent endocytosis, acidification, and reduction of transferrin-bound Fe3+ to Fe2+. The release of transferrin-derived Fe2+ was potentiated by diethyldithiocarbamate, an inhibitor of intracellular superoxide dismutase (SOD). In contrast, exogenous SOD did not alter iron release, suggesting that intracellular superoxide anion (O2-) may play an important role in mediating the reduction and release of transferrin-derived iron. Results of this study suggest that transferrin may provide a source of iron for oxygen free radical-mediated endothelial cell injury and identify a novel mechanism by which endothelial cells may mediate the reduction and release of transferrin-derived iron. PMID- 1312809 TI - Modulation of TNF-alpha-priming and stimulation-dependent superoxide generation in human neutrophils by protein kinase inhibitors. AB - Human peripheral blood polymorphonuclear leukocytes (HPPMN) from healthy individuals are not primed and, hence, weak stimulation-dependent responses are induced by certain stimuli which bind to membrane receptors. When HPPMN were exposed to recombinant human tumor necrosis factor alpha (rHuTNF-alpha) or recombinant human granulocyte colony stimulating factor (rG-CSF), they underwent priming and the rate of superoxide anion (O.-2) generation was increased by subsequent exposure to formyl-methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ). However, the degree of enhancement was very small upon exposure to phorbol myristate acetate (PMA) or dioctanoyl glycerol (DOG). The oxygen burst induced by FMLP or OZ was inhibited by genistein and alpha-cyano-3-ethoxy-4 hydroxy-5-phenylthiomethylcinnamamid (ST638), which are inhibitors of tyrosine kinase (TK), and was enhanced by 1-(5-isoquinoline-sulfonyl)-3-methyl-piperazine (H-7) and staurosporine, which are inhibitors of protein kinase C (PKC). Without priming, however, O.-2 generation from HPPMN by high concentrations of FMLP was not inhibited strongly by genistein or ST638. On the contrary, the oxygen burst induced by PMA or DOG was stimulated by genistein or ST638 and was inhibited by H 7 or staurosporine. Furthermore, O.-2 generation by guinea pig peritoneal neutrophils, which are already primed in vivo, was induced markedly by FMLP by a mechanism which was stimulated by a low concentration of genistein or ST638. Thus, FMLP-mediated O.-2-generation of HPPMN is coupled with rHuTNF-alpha- or rG CSF-priming and is inhibited by TK inhibitors, whereas PMA- or DOG-induced O.-2 generation is not coupled with TNF-alpha or G-CSF-priming and is inhibited by PKC inhibitors. These results suggest that both PKC and TK play critical roles in the regulatory mechanism of priming and NADPH-oxidase activation in neutrophils. PMID- 1312810 TI - Hydroxyl radical generation by red tide algae. AB - The unicellular marine phytoplankton Chattonella marina is known to have toxic effects against various living marine organisms, especially fishes. However, details of the mechanism of the toxicity of this plankton remain obscure. Here we demonstrate the generation of superoxide and hydroxyl radicals from a red tide unicellular organism, C. marina, by using ESR spectroscopy with the spin traps 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and N-t-butyl-alpha-phenylnitrone (PBN), and by using the luminol-enhanced chemiluminescence response. The spin-trapping assay revealed productions of spin adduct of superoxide anion (O2-) (DMPO-OOH) and that of hydroxyl radical (.OH) (DMPO-OH) in the algal suspension, which was not observed in the ultrasonic-ruptured suspension. The addition of superoxide dismutase (500 U/ml) almost completely inhibited the formation of both DMPO-OOH and DMPO-OH, and carbon-centered radicals were generated with the disappearance of DMPO-OH after addition of 5% dimethyl sulfoxide (Me2SO) and 5% ethanol. Furthermore, the generation of methyl and methoxyl radicals, which are thought to be produced by the reaction of hydroxyl radical and Me2SO under aerobic condition, was identified using spin trapping with a combination of PBN and Me2SO. Luminol-enhanced chemiluminescence assay also supported the above observations. These results clearly indicate that C. marina generates and releases the superoxide radical followed by the production of hydroxyl radical to the surrounding environment. The velocity of superoxide generation by C. marina was about 100 times faster than that by mammalian phagocytes per cell basis. The generation of oxygen radical is suggested to be a pathogenic principle in the toxication of red tide to susceptible aquaculture fishes and may be directly correlated with the coastal pollution by red tide. PMID- 1312811 TI - Bactericidal activity of alkyl peroxyl radicals generated by heme-iron-catalyzed decomposition of organic peroxides. AB - To clarify the nature of cytocidal molecular species among the radicals generated in the iron-catalyzed reactions of peroxides (ROOH), we examined the cytocidal effects of these radicals against gram-positive and gram-negative bacteria in the presence or absence of various radical scavengers. Three organic peroxides, t butyl hydroperoxide (t-BuOOH), methyl ethyl ketone peroxide (MEKOOH), and cumene hydroperoxide, were used. Each radical generated from these peroxides was identified and quantitated by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The major cytotoxic radical species generated in the mixtures of various peroxides and heme iron, especially methemoglobin, metmyoglobin, or hemin, was the alkyl peroxyl radical (ROO.). Strong bactericidal action against gram-positive bacteria was observed in the peroxide-heme iron system, especially in the case of t-BuOOH and MEKOOH. Killing curves for gram-positive bacteria showed an initial lag period, which may indicate the multihit/multitarget kinetics of cell killing. When the diethylenetriamine pentaacetic acid (DTPA)-Fe2+ complex was used as a catalyst for decomposition of various peroxides, alkyl, alkoxyl, and alkyl peroxyl radicals were identified by spin-trapping analysis. However, study of the time course of alkyl peroxyl radical production in the DTPA-Fe2+ complex system revealed that radical species generated in this system were very short lived: a maximal level was achieved within 1 min and then declined sharply, and no bactericidal activity was observed after 10 min. In contrast, the alkyl peroxyl radical level generated by the organic peroxide-heme iron system remained high for 30 min or longer. The generation of alkyl peroxyl radicals quantified by ESR correlated quite well with the bactericidal effect of the system of peroxide plus iron. In addition, bactericidal activity was completely inhibited by the addition of the spin trap DMPO, as well as of other various radical scavengers (alpha tocopherol and L-ascorbic acid), into the peroxide-heme iron system, but this effect was not observed with superoxide dismutase, beta-carotene, dimethyl sulfoxide, diphenylamine, or butylated hydroxyltoluene. In view of these results, it is assumed that alkyl peroxyl radicals are the potent molecular species that are cytotoxic against bacteria, whereas alkoxyl radicals (RO.) generated in this system do not affect bacterial viability. PMID- 1312812 TI - On the nature of leukotriene C4 synthase in human platelets. AB - Leukotriene C4 is considered to play a major role in several important pathophysiological conditions, e.g., allergy, asthma, and shock. The present investigation demonstrates the presence in human platelets of a membrane associated enzyme catalyzing the final step in the biosynthesis of leukotriene C4. This leukotriene C4 synthase was shown to be distinct from previously characterized "microsomal" and soluble glutathione transferases. The latter enzymes did not contribute significantly to the leukotriene A4 conjugating activity in platelets. As determined with leukotriene C4 synthase of a crude membrane fraction from human platelets, the Km value was 7 microM and the V value was 0.56 nmol x min-1 x mg-1 with leukotriene A4 as substrate. The enzyme was 20 fold more efficient with leukotriene A4 than with leukotriene A5 and 30-fold more efficient than with the unphysiological derivative leukotriene A4 methyl ester, as measured by the corresponding V/Km values; 14,15-leukotriene A4 was not a substrate. Platelets should be a useful source for the purification and further characterization of human leukotriene C4 synthase. PMID- 1312813 TI - The catecholic metal sequestering agent 1,2-dihydroxybenzene-3,5-disulfonate confers protection against oxidative cell damage. AB - Tiron (1,2-dihydroxybenzene-3,5-disulfonate), a nontoxic chelator of a variety of metals, is used to alleviate acute metal overload in animals. It is also oxidized to the EPR-detectable semiquinone radical by various biologically relevant oxidants, such as .OH, O2-., alkyl, and alkoxyl radicals. Since Tiron reacts with potentially toxic intracellular species and is also a metal chelator, we evaluated its protective effects in V79 cells subjected to various types of oxidative damage and attempted to distinguish the protection due to direct detoxification of intracellular radicals from that resulting from chelation of redox-active transition metals. We found that Tiron protects Chinese hamster V79 cells against both O2.(-)-induced (and H2O2 via dismutation of O2.-) and H2O2 induced cytotoxicity as measured by clonogenic assays. In experiments where Tiron was incubated with V79 cells and rinsed prior to exposure to HX/XO or H2O2, cytoprotection was observed, indicating that it protects against intracellular oxidative damage. On the other hand, Tiron did not protect V79 cells against the damage caused by ionizing radiation under aerobic conditions, which is predominantly mediated by H., .OH, and hydrated electrons in a metal-independent fashion. We demonstrate also that in in vitro studies, Tiron protects supercoiled DNA from metal-mediated superoxide-dependent strand breaks. We conclude that Tiron is a potentially useful protecting agent against the lethal effects of oxidative stress and suggest that it offers protection by chelating redox-active transition metal ions, in contrast to earlier reports where the protection by this compound in cellular systems subjected to oxidative damage has been interpreted as due to radical scavenging alone. PMID- 1312814 TI - Serum concentration and urinary excretion of "classical" estrogens, catecholestrogens and 2-methoxyestrogens in normal human pregnancy. AB - Catecholestrogens, 2-methoxyestrogens and "classical" estrogens (estrone, estradiol, estriol) were measured simultaneously in serum and urine samples of 220 pregnant women from the 8th week of pregnancy until to delivery. From these data we established the central 0.80 centile intervals as time specified reference intervals for each substance analyzed. Serum and urinary estradiol rise steadily during the progress of pregnancy, whereas estrone, catecholestrogens and 2-methoxyestrogens reach a plateau during the last trimester. These observations support the hypothesis, that the amount of the latter compounds may be regulated by separate mechanisms. The values of concentration and excretion of 2- and 4 substituted estrogens varied widely throughout pregnancy. Even very high or very low concentrations of these substances had no recognizable relation to the outcome of pregnancy. This supports the assumption that catecholestrogens and their methylethers are metabolites without any regulatory function in pregnancy. PMID- 1312815 TI - White blood cell activation in Raynaud's phenomenon of systemic sclerosis and vibration induced white finger syndrome. AB - Systemic sclerosis (SSc) and vibration induced white finger syndrome (VWF) are common causes of secondary Raynaud's phenomenon. Previous studies have suggested an increase in inflammation in patients with SSc. Vibration induced white finger syndrome occurs in workers exposed to vibration and is now a prescribed disease. In VWF, although it is recognised that vibration can cause direct damage to blood vessels, it does not explain why only some workers are affected. It is possible that an inflammatory process develops in these patients in the same way as is seen in SSc. Leukotriene B4, produced mainly by polymorphonuclear cells, is a potent mediator of inflammation. The plasma thiol concentration shows the degree of oxidation of plasma and a decreased concentration indicates the increased production of free radicals which are capable of oxidative damage. In this work, the white blood cell (WBC) production of leukotriene B4 and plasma thiol concentrations were measured in patients with SSc and VWF. Fifty nine patients were studied: 34 had SSc and 25 had VWF. The results were compared with 25 matched normal controls and are expressed as the median and range. After stimulation of the polymorphonuclear cells with calcium ionophore A23187 (1 microgram/ml), patients with SSc and VWF were found to have significantly increased leukotriene B4 production (23.5 (14.4-44.0) and 26 (14.4-39.4) ng/10(6) cells, respectively) compared with normal controls (17.2 (6.0-38.0) ng/10(6) cells). The plasma thiol concentration was shown to be significantly lower in patients with SSc and VWF (445 (375-475) and 450 (417-510) mumol/l, respectively) compared with normal controls (480 (418-555) mumol/l). Our results show increased leukotriene B4 production and increased free radical activity in patients with SSc and VWF. Although previous indirect evidence has suggested increased WBC activity in patients with SSc, this is reported directly here for the first time. In addition, the possibility of an inflammatory process occurring in patients with VWF, as shown here, has not previously been studied. This may be a further mechanism to explain the poor circulation in the fingers of these patients. PMID- 1312816 TI - Structure of the sugar-phosphate moiety of lipid A from lipooligosaccharide of Neisseria meningitidis group B, strain BC5S No. 125. Hydrolytic stability of phosphate and pyrophosphate substituents. AB - On the basis of chemical and NMR data the partial structure of lipid A from lipooligosaccharide (LOS) of Neisseria meningitidis group B, strain BC5S No 125 was established. Lipid A consisted of disaccharide 2-deoxy-6-O-[2-deoxy-2-(3 hydroxytetradecanoylamino)- beta-gluco-pyranosyl]-2-(3-hydroxytetradecanoylamino) alpha-glucopyranose carrying the beta-(2-aminoethyl)pyrophosphate residue at 0 4' and the pyrophosphate or phosphate residue at 0-1. On hydrolysis of the acidic form of LOS with 1% acetic acid the substituent at 0-1 was practically completely removed whereas that at 0-4' was stable. The analogous hydrolysis of the Mg-salt of LOS was accompanied by splitting off the pyrophosphate linkage in the substituent at 0-4'. Hydrolysis of LOS at pH 4.5 in the presence of SDS led mainly to a lipid A preparation retaining both pyrophosphate residues. PMID- 1312818 TI - Bile and the growth of intestinal polyps. PMID- 1312817 TI - Total vascular exclusion for hepatic resection in cirrhotic patients. Application of venovenous bypass. AB - Hepatic vascular exclusion with double venovenous bypass using a centrifugal force pump was used in major hepatic resections in eight patients with hepatocellular carcinoma combined with cirrhosis, and results were compared with those in four patients with hepatocellular carcinoma without cirrhosis and eight with metastatic tumors without cirrhosis among 521 patients undergoing liver resection. Concomitant resection of the retrohepatic inferior vena cava was performed in three of eight patients with cirrhosis and five of 12 patients without cirrhosis. All patients, except one with cirrhosis, tolerated major resection without any hemodynamic impairment, which is often observed in hepatic vascular exclusion without venovenous bypass. One patient, whose complete inflow occlusion period was 70 minutes, died of liver failure. In this patient, the recovery of the arterial ketone body ratio above 1.0 was delayed until 3 days after recirculation, whereas the ratio in the others recovered promptly. Postoperative complications such as increased bilirubin level, pleural effusion, and gastrointestinal tract bleeding were observed in seven of eight patients with cirrhosis compared with six of 12 without cirrhosis. Hepatic vascular exclusion is feasible even in cirrhotics as long as it is applied with venovenous bypass and is kept within the time limit of 60 minutes. PMID- 1312819 TI - Localization of herpes simplex virus type 1 in sebaceous glands of mice. AB - The distribution of HSV-1 during the development of zosteriform skin lesions in SCID mice was analyzed by immunofluorescence and electron microscopy. The virus initially appeared within certain keratinocytes, sometimes surrounded by keratinocytes whose surfaces were also positive for the antigens, in the lower epidermal layers including the hair follicles, and then extended upward to the entire epidermis and downward to the sebaceous glands 1-2 days later, when no macroscopic skin lesion was seen. The affected epidermal cells subsequently degenerated and lost their viral antigens within a day, when the zosteriform lesion then became evident. This was followed by a degeneration of the dermis. The sebaceous glands eventually degenerated in 10 days, but some glands in the necrotic skin areas preferentially retained HSV-1. The horizontal spread of the virus in the epidermis beyond the first invaded dermatome occurred much later. In mice passively immunized with specific immune serum, viral antigens were observed even 20 days after the infection in sebaceous glands in necrotized areas. Therefore, HSV-1 appears to spread first via the extracellular fluid among the keratinocytes after being shed from nerve endings, and then produces a successive degeneration of the affected keratinocytes which may prevent any further extension of horizontal viral spread. The pilosebaceous apparatus is possibly acting as a site not only for the replication of HSV-1 with a delayed cytopathic effect, but also as an area that is temporarily sheltered from host defense mechanisms. PMID- 1312820 TI - Correlation between gI, gII, gIII, and gp 50 antibodies and virus excretion in vaccinated pigs infected with pseudorabies virus. AB - Eleven groups of 8 pigs were vaccinated with different vaccinal strains of pseudorabies virus deleted or not for non-essential glycoproteins (gI, gX, gp 63), then were challenged 8-9 weeks later with a virulent strain. Antibodies against the major viral glycoproteins (gII, gIII, gp 50) were titrated at the day of challenge. Excretion of the challenge strain, growth performance of the pigs, and gI antibody responses from pigs vaccinated with a gI minus strain, were monitored after the challenge. The results demonstrated a strong association between gII and gIII antibody titres before the challenge, with the amount of the challenge strain excreted and clinical protection after the challenge. Furthermore, gI antibody titres after the challenge were negatively correlated with the level of gII and gIII antibodies at the day of challenge, the virus excretion and the clinical protection after the challenge. Implications of these results for vaccination of pigs and gI antibody screening for the infection are discussed. PMID- 1312821 TI - Infectious laryngotracheitis virus growth, DNA replication, and protein synthesis. AB - The polypeptides associated with infection of primary chicken kidney (CK) cells with infectious laryngotracheitis virus (ILTV) were examined by metabolic labelling with [35S]methionine and SDS-PAGE. Polypeptide synthesis was followed over the first 24 h post-infection (p.i.) as this was shown to be the period of viable virus production. A total of 16 ILTV encoded or induced polypeptides were identified using metabolic labelling. The use of inhibitors of protein and DNA synthesis in conjunction with metabolic labelling and viral DNA replication studies enabled a cascade pattern of gene expression, similar to that of herpes simplex virus type 1 (HSV-1), to be established for ILTV. Representatives of alpha, beta, gamma 1 and gamma 2 classes of genes were identified. In contrast to infection with HSV types 1 and 2, which leads to a rapid inhibition of total host cell polypeptide synthesis, ILTV infection of CK cells did not result in a complete inhibition of cellular protein synthesis, with only a small number of host cell polypeptides absent from infected cells. PMID- 1312822 TI - Herpes simplex virus type 1 (HSV-1) HSZP interferes also after antibody neutralization with early shutoff of host protein synthesis induced by HSV-1 KOS. AB - The HSZP strain of herpes simplex virus type 1 (HSV-1) is defective with respect to the early shutoff of host protein synthesis. However, in superinfection experiments using Vero cells, the HSZP strain was effective, even after neutralization by antibody, at interfering with the early shutoff function of the HSV-1 KOS strain. Evidence was given that the observed interference was not due to exclusion of the KOS by HSZP at the level of adsorption or penetration. The neutralized KOS strain failed to induce early shutoff of host protein synthesis. PMID- 1312824 TI - In vitro recognition of an orf virus early promoter in a vaccinia virus extract. AB - DNA fragments containing varying lengths of the 5' end of an orf virus early gene (ORF3) and its associated promoter were introduced into sodium deoxycholate solubilized vaccinia virus extracts capable of initiating transcription in vitro from vaccinia virus early promoters. After separation of the radiolabelled products of the reactions on a 5% polyacrylamide/7 M urea gel, discrete transcripts were detected the sizes of which were consistent with initiation of transcription from the orf virus early promoter. This is the first demonstration in a functional assay of the conservation of early transcriptional promoters between an orthopoxvirus and a parapoxvirus. PMID- 1312823 TI - Restriction endonuclease and genetic mapping studies indicate that the vegetative genome of the temperate, Salmonella-specific bacteriophage, epsilon 15, is circularly-permuted. AB - Data from physical and genetic mapping studies show that the vegetative genome of the temperate, Group E 1 Salmonella bacteriophage, epsilon 15, is circularly permuted. Preliminary evidence suggests that the circular permutation of the epsilon 15 genome is non-random. PMID- 1312825 TI - Molecular characterization and heterogeneity of feline immunodeficiency virus isolates. AB - We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone can not infect Crandell feline kidney cells which were permissive for FIV Petaluma. The amino acid sequence homologies, in gag, pol, and env genes between FIV TM2 and Petaluma were 90%, 87%, and 81%, respectively. On the other hand, comparative analysis of each gene between FIV Petaluma and PPR showed 96,95, and 85%, respectively. These results suggested that the genomic diversity was present among FIV strains isolated from geographically distant areas. Interestingly, tat- and rev-like short open reading frames contained inframe stop codons in the FIV Petaluma but not in the FIV TM2. PMID- 1312827 TI - Mesenteric fibromatosis preventing restorative proctectomy. AB - A case is reported illustrating the dilemma of encountering mesenteric fibromatosis during restorative proctectomy for familial adenomatous polyposis. PMID- 1312826 TI - The effects of beta-2-microglobulin on the infectivity of murine cytomegalovirus. AB - The role of beta-2-microglobulin (beta 2m) in murine cytomegalovirus (MCMV) infection of susceptible (H-2d) and resistant (H-2k) murine embryo fibroblasts (MEF) and peritoneal macrophages was evaluated using serum-free virus (SF-MCMV). The infectivity of SF-MCMV was significantly lower than virus propagated in serum, although the concentrations of virions were similar. Infection of cells with SF-MCMV was assessed by measuring the proportion of cells expressing viral antigens, the sizes of plaques formed in fibroblast monolayers and TCID50 titers. Infection of susceptible fibroblasts was significantly increased 1.6-4.7 fold by the addition of whole FCS, a less than 20 kDa FCS fraction, or purified human beta 2m. These supplements also significantly enhanced infection of susceptible macrophages and increased TCID50 titers by 3.5-10 fold in susceptible MEF. In relatively resistant H-2k cells, the TCID50 titer and the proportion of cells expressing viral antigens after infection with SF-MCMV were not affected by beta 2m or FCS, but plaque sizes were increased 2.5-3 fold in resistant BALB.K MEF. When human or murine beta 2m was added to infected cultures, immunogold electron microscopy revealed these proteins to be always associated extracellularly with the tegument material of disrupted multicapsid virions, but rarely with the envelope of intact virions. However, no murine beta 2m was found in association with the envelope or tegument of SF-MCMV. These relatively modest effects of beta 2m which were restricted to genetically susceptible cells, may be due to tegument bound beta 2m facilitating infection by capsids, or the stabilisation of the conformation of Class 1 molecules by exogenous beta 2m, promoting MCMV binding to the target cell. PMID- 1312828 TI - Rat lung possesses the mineralocorticoid receptor. AB - Lung cytosol from male, adrenalectomized rats was screened for the mineralocorticoid receptor (MCR) by a polyclonal antiserum raised in the rabbit against rat renal antigen. Western blot analysis revealed a single 98 kDa band, like the MCR purified biochemically. The MCR could also be photolabelled for the first time by 3H-R 5020 in this very 98 kDa region that was displaced by RU 26752 specific to MCR. Immune IgG was able to precipitate the MCR-3H-RU 26752 complex, and to displace the same to high molecular weight regions during gel permeation chromatography on Sephacryl columns. Thus, MCR mediated actions need to be redefined. Furthermore, the technique of photochemical labelling forms a novel tool to assess MCR specificity, and to dissect its structure and function. PMID- 1312829 TI - Expression and transforming activity of a variant of the heparin-binding fibroblast growth factor receptor (flg) gene resulting from splicing of the alpha exon at an alternate 3'-acceptor site. AB - Splicing at an alternate 3'-acceptor site results in deletion of a CCCAG in the 5'-sequence of the exon coding for the NH2-terminal immunoglobulin-like disulfide loop of the heparin-binding fibroblast growth factor receptor (flg) alpha isoform. The result is an in-frame stop codon 138 base pairs after the first flg consensus translational initiation site. The next more favorable site predicts the same two loop intracellular receptor isoform, gamma, which was predicted from two different human cDNAs that arise by alternate use of two exons at the same site. Although expressed in normal tissue, the gamma mRNA is increased in rat prostate tumors and confers ability of anchorage-dependent cells expressing non secreted heparin-binding fibroblast growth factors to grow in soft agar. PMID- 1312830 TI - Protamine kinase phosphorylates eukaryotic protein synthesis initiation factor 4E. AB - Up to 1 mol of phosphoryl groups was incorporated per mol of eukaryotic protein synthesis initiation factor (eIF) 4E following incubation of purified preparations of this factor with purified preparations of a protamine kinase from bovine kidney cytosol. By contrast, purified preparations of two forms of mitogen activated protein kinase, casein kinase II and two forms of a distinct autophosphorylation-activated protein kinase exhibited little activity, if any, with eIF-4E. Together with previous observations, the results indicate that the protamine kinase could contribute to the insulin-stimulated phosphorylation of eIF-4E. PMID- 1312831 TI - The reducing activity of S-aminoethylcysteine ketimine and similar sulfur containing ketimines. AB - S-aminoethylcysteine ketimine and other sulfur-containing similar ketimines reduce molecular oxygen and phospho-18-tungstate (Folin Marenzi reagent), although the sulfur atom is formally present in the non reducing thioether form. We have now found that 2,6-diclorophenolindophenol, some ferrihemoproteins and other reagents are also reduced by this group of ketimines. Ferricytochrome c is reduced faster than methemoglobin, metmyoglobin and free hematin, whereas horse radish peroxidase compound I is reduced at once. These results indicate a wider reducing activity of this type of ketimine. The oxidation of ketimines by ferric cytochrome c appears a relevant finding pointing to a new possible way of enzymatic modification of sulfur-ketimines in tissues. PMID- 1312832 TI - Plasma membrane calcium pump expression in human placenta and small intestine. AB - To identify the forms of the plasma membrane calcium pump present in tissues that transport calcium, cDNA from human placenta and proximal small intestine was amplified by the polymerase chain reaction using a pair of mixed primers based on all the known human and rat plasma membrane calcium pump sequences. Clones were identified from the two human forms HPMCA1 and HPMCA4, but no new sequences were found in either tissue. RNA blots probed with HPMCA1 showed two bands in both tissues; probing with HPMCA4 gave a single, larger species. In placenta, HPMCA4 was the more abundant form and similar expression was found in full-term and second-trimester placentas. In contrast, in the small intestine, HPMCA1 was more abundant, suggesting that calcium absorption is not associated with any one specific isoform in calcium transporting cells. PMID- 1312833 TI - Endothelin and structurally related analogs distinguish between endothelin receptor subtypes. AB - The endothelin (ET) analog ET-1[1,3,11,15-Ala] was compared with ET-1, ET-2, ET-3 and sarafotoxins (SRTX) S6b and S6c for receptor binding and function. All the peptides exhibited high affinity binding and contracted rabbit pulmonary artery with near equal potency. In rat aorta both ET-3 and ET-1 [1,3,11,15-Ala] bound with much lower affinity than ET-1 while ET-3 displayed weak contractile potency and ET-1 [1,3,11,15-Ala] and SRTX-c were inactive. In rat left atria, ET-1 [1,3,11,15-Ala] and SRTX-c were weak inhibitors of binding and were also functionally inactive, whereas ET-1, ET-2, ET-3, and SRTX-b were equipotent in producing contractile responses. The data support the idea of there being a predominance of ETA receptors in rat aorta and ETB receptors in rabbit pulmonary artery. In rat left atria, the ET receptor could not be readily classified into ETA or ETB and suggests the existence of a new receptor subtype. PMID- 1312834 TI - Identification of guanidino succinate as a putative endogenous source of the endothelium derived relaxing factor. AB - Using a specific HPLC analysis for guanidines, we find that rat aorta contains guanidino succinate (GS), guanidino acetate (GA), guanidino propionate (GP), guanidino butyrate (GB), methyl guanidine (MG) and guanidine. The concentration of L-arginine (0.05 nmol/mg tissue) is significantly lower than the other guanidines. GS is found to be the most potent vasodilator-guanidine in the rat aorta preparation and this vasodilation depends predominantly on the presence of the endothelium. This effect of GS is antagonized by NG-monomethyl L-arginine (L NMMA), NW-nitro L-arginine benzyl ester (L-NABA), hemoglobin and by methylene blue, all of which are known to block or attenuate endothelium dependent relaxation. Further, the relaxation mediated by GS is accompanied by the formation of cGMP in the rat aorta. From these results we suggest that GS may be a major endogenous source of EDRF. PMID- 1312836 TI - Is the osteoclast calcium "receptor" a receptor-operated calcium channel? AB - Elevated extracellular calcium levels ([Ca2+]e) inhibit osteoclast function by elevating cytosolic free calcium levels ([Ca2+]i), presumably via the activation of a surface Ca2+ "receptor". It is unclear whether or not Ca(2+)-induced [Ca2+]i elevation involves the direct gating, by the putative "receptor", of a divalent cation channel. The results show that [Ca2+]i elevation in response to elevated [Ca2+]e comprises a distinct component of Ca2+ influx, the magnitude of which can be decreased and increased, respectively, by depolarising (100 mM-[K+]) and hyperpolarising (1 microM-[valinomycin]) the osteoclast membrane. In addition, activation of the putative Ca2+ "receptor" by elevated [Ca2+]e causes influx of the related divalent cation, magnesium (Mg2+). We suggest that Ca2+ influx induced by Ca2+ "receptor" activation is a major component of the observed [Ca2+]i response. PMID- 1312835 TI - Protease inhibitors but not proteases inhibit the glucose-6-phosphatase of native rat liver microsomes. AB - Controlled proteolytic digestion by trypsin or bacterial proteases limited to the cytosolic side of the native microsomal membrane is not efficient to inhibit glucose-6-phosphate hydrolysis. Modification of the microsomes with deoxycholate prior to protease treatment is prerequisite to allow accessibility of the integral protein and inhibition of enzyme activity. Glucose-6-phosphatase of native microsomes, however, is rapidly inactivated by micromolar concentrations of TPCK as well as TLCK. In deoxycholate-modified microsomes both reagents do not affect glucose-6-phosphate hydrolysis. These results indicate that in the native, intact microsomal membrane glucose-6-phosphatase is not accessible to proteolytic attack from the cytoplasmic surface. The putative inhibitory effect of some trypsin or bacterial protease preparations on glucose-6-phosphatase of native microsomes observed most possibly is a result of contaminating agents as TPCK or TLCK. PMID- 1312837 TI - A Ca2+ calmodulin dependent kinase rather than protein kinase C is involved in up regulation of the LHRH receptor. AB - Stimulation of protein kinase C (PKC) by phorbol ester (PMA) was reported previously to increase total binding of the peptide in whole rat pituitary cells. The effect could be obtained in cells from intact, not from spayed animals, suggesting a different level of spontaneous phosphorylation in both conditions. In the present work, endogenous PKC was desensitized in pituitary cells sampled from intact or 3 weeks castrated male rats and maintained in primary culture. Desensitization was induced by overnight incubation with 1 microM PMA. The maximum number of plasma membrane LHRH receptors (Bmax) present on cells from in intact animals was higher (+ 98 +/- 9%) when binding was performed at 0.5 degrees C instead of 21 degrees C as already observed in non PKC-desensitized cells. PMA (100 nM) was ineffective to increase Bmax, suggesting effectiveness of enzyme desensitization. In contrast, ionomycin 1 microM increased Bmax (53 +/- 10%). This increment was inhibited by W7, a calmodulin inhibitor, with an IC50 = 1 +/- 0.35 10(-6) M. No temperature dependency of the Bmax was observed in cells from castrated rats as already shown in the absence of PKC desensitization. Under these conditions, a Bmax decrease of 34 +/- 6% and 36.5 +/- 7.5% respectively was observed in the presence of H7, a PKC inhibitor, or of W7 (IC50 = 1 +/- 0.5 10( 5) M and IC50 = 0.8 +/- 0.2 10(-6) M). We conclude that a Ca2+ calmodulin dependent protein kinase rather than PKC itself is responsible for unmasking LHRH receptors. PMID- 1312839 TI - Characterization of the promoter region of the murine fibroblast growth factor receptor 1 gene. AB - To obtain some clue for the regulatory mechanism by which fibroblast growth factor (FGF) receptor 1 (FGFR 1) gene is expressed, we have cloned the promoter region of this gene from genomic library of mouse FGF-responsive cell lines. The genomic clone isolated here includes the FGFR 1 gene from position -868 to +697 relative to transcription initiation site. Sequence analysis reveals the presence of various consensus sequences for the binding sites of transcriptional factors such as SP 1, GCF, Oct-I, AP 1 and AP 2, but the absence of TATA and CAAT sequence motif. The transfection of this promoter-CAT constructs into NIH 3T3 cells demonstrates its promoter activity which is at least located between base 106 and +104. PMID- 1312838 TI - Molecular cloning and characterization of a novel rat activin receptor. AB - We report the isolation of a full-length rat cDNA for a new activin receptor. The deduced amino acid sequence of this receptor shows 67 percent overall identity with that of a previously identified mouse activin receptor. As predicted for the mouse activin receptor, the amino acid sequence of the rat receptor is consistent with a polypeptide containing an extracellular ligand binding domain, a hydrophobic transmembrane domain, and a serine/threonine kinase intracellular domain. In an expression assay, this new receptor was found to bind I125 radiolabeled activin. PMID- 1312840 TI - Calmodulin-binding proteins of calcium-independent type in rat brain synaptosomal membranes: their localization and properties. AB - Some properties of calmodulin(CaM)-binding proteins (CaMBPs) of the Ca(2+) independent type were investigated in the synaptosomal membrane (SM) from rat brain using the [125I]CaM gel overlay method. When SM was prepared in the presence of Ca2+, Ca(2+)-independent CaM binding was decreased, whereas the Ca(2+)-dependent type was not altered. All Ca(2+)-independent-type CaMBPs were membrane-bound and scarcely present in the soluble fractions. When SM was heat denatured, the 24/22.5-kDa CaMBPs could no longer be detected by [125]CaM binding and a new component with higher molecular mass (greater than 200 kDa) was shown to bind CaM in a Ca(2+)-independent manner. A possible effect of cAMP- and Ca2+/CaM-dependent phosphorylation on CaM binding was also examined. PMID- 1312841 TI - Reactivation of denatured fungal glucose 6-phosphate dehydrogenase and E. coli alkaline phosphatase with E. coli ribosome. AB - Fungal glucose 6-phosphate dehydrogenase and E. coli alkaline phosphatase were denatured either by physical or by chemical means. In vitro reconstitution of these denatured enzymes was assisted by 70S E. coli ribosome, as shown by the recovery of their catalytic competence. Almost total recovery of the activities of completely inactivated enzymes was obtained when 70S ribosome was present at about equimolar concentration with the enzyme molecules at 37C and 50C, respectively. PMID- 1312842 TI - Whole rat electron paramagnetic resonance imaging of a nitroxide free radical by a radio frequency (280 MHz) spectrometer. AB - Low frequency (280 MHz) electron paramagnetic resonance spectroscopy has been used to follow uptake, distribution and reduction of the nitroxyl spin label PCA in the rat. No difference of half life was found in seven rats submitted to three administrations of PCA (11.3 +/- 0.4; 11.0 +/- 0.6 and 11.5 +/- 0.7 min). Transversal two-dimensional images of PCA distribution in the rat body were obtained over 6 min by means of field gradients. PCA was observed in three regions by projections along the longitudinal axis of the rat. PCA accumulation was found in the lower abdomen 12 min after the start of the PCA injection. PMID- 1312843 TI - Protein kinase C activity in neonatal cultured rat cardiomyocytes supplemented with docosahexaenoic acid. AB - In vitro studies have indicated that the 1-stearoyl, 2-arachidonyl diacylglycerol (DAG) is the most effective one for the activation of protein kinase C, although many other DAGs having a different fatty acid composition are active, but to a different extent. Using cultures of neonatal rat ventricular cells, grown in a medium enriched in docosahexaenoic acid (DHA), we previously obtained a cell population that, after alpha 1-adrenoceptor stimulation, produced a DHA enriched DAG. In this study, we have tested the "in vivo" ability of this modified DAG as protein kinase C activator, demonstrating a lower but more persistent translocation of the enzyme from cytosol to particulate fraction in the DHA treated cells. The differences in the PKC activation pattern could be explained by a different metabolism of the DHA enriched DAG by DAG kinase. PMID- 1312844 TI - Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor alpha on hepatitis B virus enhancer activity. AB - The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg. PMID- 1312846 TI - Cumulative trauma disorders--an overview. AB - 1. CTDs are a major problem in some industries. Evidence exists for an association between symptoms of CTDs and occupational risk factors such as forceful exertion, repetitiveness, vibration, cold, and extreme postures. 2. The efficacy of ergonomic interventions or programs in reducing CTDs must be evaluated using the same methods as those used to identify problems initially; user feedback regarding job or tool redesigns is essential. Implementing ergonomic interventions is an ongoing, iterative process. 3. The ability of the occupational health nurse to carry out basic nursing functions of health promotion and prevention of injury and illness will be enhanced through the application of the principles of ergonomics. PMID- 1312845 TI - Single vs. repeated microwave exposure: effects on benzodiazepine receptors in the brain of the rat. AB - We studied the effects of single (45 min) and repeated (ten daily 45-min sessions) microwave exposures (2450-MHz, 1 mW/cm2, average whole-body SAR of 0.6 W/kg, pulsed at 500 pps with pulse width of 2 microseconds) on the concentration and affinity of benzodiazepine receptors in the cerebral cortex, hippocampus, and cerebellum of the rat. We used a receptor-binding assay with 3H-flunitrazepam as ligand. Immediately after a single exposure, an increase in the concentration of receptor was observed in the cerebral cortex, but no significant effect was observed in the hippocampus or cerebellum. No significant change in binding affinity of the receptors was observed in any of the brain-regions studied. In rats subjected to repeated exposures, no significant change in receptor concentration was found in the cerebral cortex immediately after the last exposure, which may indicate an adaptation to repeated exposures. Our data also show that handling and exposure procedures in our experiments did not significantly affect benzodiazepine receptors in the brain. Because benzodiazepine receptors in the brain are responsive to anxiety and stress, our data support the hypothesis that low-intensity microwave irradiation can be a source of stress. PMID- 1312847 TI - Ethanol inhibition of the chemiluminescent response of stimulated macrophages. AB - The effect of ethanol on the luminol-dependent chemiluminescence and cAMP level in mice peritoneal macrophages was investigated. Ethanol was shown to inhibit the chemiluminescence of macrophages by acting both as a "trap" for active radicals and as a suppressor of the cellular functional activity. A short preincubation of macrophages with ethanol results in a dose-dependent decrease of the chemiluminescent response to the stimulatory agent (opsonized zymosan). Ethanol was also shown to induce a peakwise rise of the intracellular cAMP after a 2-min incubation. The observed effects are correlated both in time and concentration, which allows the presumption that inhibition of the functional activity of macrophages is mediated by the increase of the intracellular cAMP level. PMID- 1312848 TI - Differential G protein-mediated coupling of D2 dopamine receptors to K+ and Ca2+ currents in rat anterior pituitary cells. AB - In anterior pituitary cells, dopamine, acting on D2 dopamine receptors, concomitantly reduces calcium currents and increases potassium currents. These dopamine effects require the presence of intracellular GTP and are blocked by pretreatment of the cells with pertussis toxin, suggesting that one or more G protein is involved. To identify the G proteins involved in coupling D2 receptors to these currents, we performed patch-clamp recordings in the whole-cell configuration using pipettes containing affinity-purified polyclonal antibodies raised against either Go alpha, Gi3 alpha, or Gi1,2 alpha. Dialysis with Go alpha antiserum significantly reduced the inhibition of calcium currents induced by dopamine, while increase of potassium currents was markedly attenuated only by Gi3 alpha antiserum. We therefore conclude that in pituitary cells, two different G proteins are involved in the signal transduction mechanism that links D2 receptor activation to a specific modulation of the four types of ionic channels studied here. PMID- 1312849 TI - Exogenous synapsin I promotes functional maturation of developing neuromuscular synapses. AB - We have investigated the possible role of synapsin I, a nerve terminal-specific protein, in the maturation of neuromuscular synapses in Xenopus cell cultures. Purified synapsin I was loaded into embryonic spinal neurons by injection of the protein into one of the early blastomeres of a Xenopus embryo. At synapses made by synapsin I-loaded neurons, spontaneous synaptic currents occurred with higher frequency and amplitude, and the amplitude exhibited an earlier appearance of a bell-shaped distribution. These characteristics are indicative of more mature quantal secretion. Impulse-evoked synaptic currents also showed a significant increase in amplitude. Using cell manipulation techniques, enhanced transmitter release from synapsin I-loaded neurons was shown to occur at the onset of synaptogenesis, suggesting a presynaptic developmental action of synapsin I prior to synaptic contact. Taken together, these results suggest that endogenous synapsin I may participate in the functional maturation of synapses. PMID- 1312850 TI - Mechanisms of p185HER2 expression in human non-small cell lung cancer cell lines. AB - To identify mechanisms that allow p185HER2 expression in lung cancer, we performed Western, Southern, and Northern blot analyses of 14 cell lines derived from human non-small cell lung carcinomas and one cell line derived from a human mesothelioma. Human bronchiole epithelial cells and rat type II pneumocytes were found to express p185HER2 at low to undetectable levels by Western blot technique. In contrast, 13 lung cancer cell lines expressed p185HER2, and eight of these 13 expressed p185HER2 at levels at least 2-fold higher than that found in normal bronchiole epithelial cells or type II pneumocytes. Genomic Southern analysis showed that amplification of the HER2 gene was present in only one of the eight cell lines that expressed p185HER2 at these higher levels. Increased levels of steady-state HER2 mRNA occurred in the remaining seven cell lines. We conclude that in human non-small cell lung carcinoma cell lines the most common mechanism resulting in increased p185HER2 expression is due to mechanisms that increase HER2 mRNA levels, with HER2 gene amplification occurring less commonly. PMID- 1312851 TI - Enhanced generation of free radicals from phagocytes induced by mineral dusts. AB - Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an important factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, and nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-tert-butyl nitrone (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase-glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amosite, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface properties, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos induced cell injury. PMID- 1312852 TI - Alterations in eicosanoid production by rat alveolar type II cells isolated after silica-induced lung injury. AB - Although alveolar type II cells in primary culture have been shown to produce eicosanoids and exposure of type II cells to silica in vitro alters eicosanoid production, the production of eicosanoids by alveolar type II cells isolated after acute lung injury in vivo has not been evaluated. Therefore, we investigated the production of arachidonic acid (AA) metabolites by alveolar type II cells isolated after silica-induced lung injury. Alveolar type II cells were isolated from rats 14 days after intratracheal silica instillation and from untreated animals. Type II cells were separated into normotrophic and hypertrophic populations by centrifugal elutriation, and secreted eicosanoids were determined under basal and stimulated conditions by enzyme immunoassay on the day of isolation and after 1 day in culture. Under basal conditions, freshly isolated type II cells from silica-treated animals produced more prostaglandin (PG) E2 than 6-keto-PGF1 alpha or thromboxane B2 (TxB2). Production of all three prostanoids increased with increasing cell size. The calcium ionophore A23187 stimulated a less than 2-fold increase in PGE2 and 6-keto-PGF1 alpha production in all groups of cells. In contrast, this calcium ionophore greatly enhanced TxB2 and leukotriene C4 (LTC4) production by normotrophic type II cells from both untreated and silica-treated animals. Incubation with exogenous AA suggested that the increased capability of the hypertrophic cells to synthesize PGE2 and TxB2 was due primarily to an increase in arachidonate availability. The hypertrophic type II cells also appear to have increased prostacyclin synthase activity. There were no differences in the catabolism of PGE2 between the normotrophic and the hypertrophic type II cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312853 TI - The effect of saturation of ACE binding sites on the pharmacokinetics of enalaprilat in man. AB - 1. Eight healthy male volunteers received oral enalapril, 10 mg, in the presence and absence of pretreatment with captopril, 50 mg, twice daily for 5 days. 2. Enalaprilat pharmacokinetics were characterised after both doses of enalapril to investigate the effect of saturating ACE binding sites by pretreatment with captopril. 3. The pharmacokinetics of enalaprilat were best described by a one compartment model with zero order input incorporating saturable binding to plasma and tissue ACE. 4. Values of AUC (0.72 h) for enalaprilat were 419 +/- 97 and 450 +/- 87 ng ml-1 h in the presence and absence of captopril, respectively. The difference was not statistically significant nor were there any other differences in model parameters. 5. Induction of ACE by captopril resulting in an increase in the number of ACE binding sites, may have obscured any effect of captopril on the occupancy of ACE binding sites by enalapril. PMID- 1312855 TI - Itraconazole concentrations in airway fluid and tissue. PMID- 1312856 TI - Genital human papillomavirus infections in adolescents: implications for evaluation and management. AB - Genital infections caused by human papillomaviruses (HPV) have become the most prevalent sexually transmitted disease in the United States. Rates of infection with these agents are particularly high among adolescents. The most common clinical expression of genital HPV infection is condyloma acuminata, a condition that dermatologists are frequently called on to treat. The identification of external genital warts in a teenager raises questions that impact directly on the patient's evaluation and management. Issues of importance include the likelihood that occult infection exists at other sites in the genital tract, the risks associated with HPV infection, and the need, if any, for further diagnostic assessment, including that necessary to detect the presence of coexisting sexually transmitted infections. This article examines these and associated issues and provides information that will be of value to the dermatologist caring for adolescent patients with genital warts. PMID- 1312854 TI - Lisinopril and nifedipine administration inhibits the ex vivo uptake of [45Ca2+] by platelets from hypertensive diabetic patients. AB - 1. The effect of administration of the angiotensin converting enzyme inhibitor (ACEI), lisinopril (Carace; 10-40 mg twice daily) and the calcium channel blocker, nifedipine (Adalat Retard; 20-40 mg twice daily) on ex vivo [45Ca2+] uptake by platelets from hypertensive diabetic (type 1 and 2) patients was investigated. 2. At the end of at least 3 months treatment, blood was collected prior to the patient taking the morning dose of medication and washed platelets prepared. [45Ca2+] uptake was monitored following the addition of adrenaline, isoprenaline and dibutyryl cAMP (dbcAMP), as well as in unstimulated (zero) platelets. 3. Both nifedipine and lisinopril significantly inhibited the ex vivo uptake of [45Ca2+] by platelets when this process was stimulated by adrenaline, isoprenaline and dibutyryl cAMP. Basal uptake was also inhibited in both groups. 4. These data consolidate the hypothesis that ACE inhibitors may possess calcium channel/calcium mobilisation blocking properties. Apart from its hypertensive action, lisinopril may also reduce platelet activity via modulation of calcium dynamics, thereby reducing the incidence of vascular complications associated with diabetes mellitus. PMID- 1312857 TI - Prognostic value of flow cytometrically determined DNA-ploidy, intracellular pH and esterase activity of non-small cell lung carcinomas. AB - 30 surgical specimens of patients with non-small cell lung carcinomas (NSCLC) were investigated. Significant increases of intracellular pH values in epithelial and inflammatory cells, in the percentage of dead epithelial and inflammatory cells and in the cell volume of vital inflammatory cells in cancerous lung tissue were encountered. Furthermore, decreases of the esterase activity of vital epithelial cells and of the percentage of free cell nuclei were observed. The DNA aneuploidy in 36.6% of the tumours was frequently associated with non-squamous cell carcinomas and stage II, III, IV tumours. Patients with DNA aneuploid tumours had a significantly shorter survival rate than those with DNA euploid tumours. Within the different tumour stages a similar tendency was observed which was, however, only significant in stage III tumour patients. Stage III tumours constitute therefore a heterogeneous entity with a worse prognosis for DNA aneuploid tumour patients. The intracellular pH values and esterase activity as well as the cell volume, the percentage of free cell nuclei and dead inflammatory or epithelial cells contained no significant prognostic information. PMID- 1312858 TI - Characterization of the multiple EPR line shapes of iron-semiquinones in photosystem 2. AB - We have compared the temperature-dependence characteristics of the EPR signals of Qa and Qb iron-semiquinones from both purple bacterial and plant photosystems. The data obtained were analyzed and estimates of the splitting parameters of the non-heme Fe2+ spin sublevels obtained. The study confirms the similarities of the g = 1.8 Qa iron-semiquinone signal (D/k = 15.6 K, E/k = 3.3 K) formed in formate treated plant photosystem 2 to the signal found in purple bacteria. However, the g = 1.9 Qa iron-semiquinone signal (D/k = 7.1 K, E/k = much less than 1 K), formed in photosystem 2 when bicarbonate remains bound, has a unique temperature behavior. A series of spectral features associated with the iron-semiquinone in bicarbonate-bound photosystem 2 appear as the temperature is lowered, and the analysis of these data requires that some of these features be assigned to the higher spin states. The results are discussed in terms of the requirement for bicarbonate to be a ligand of the non-heme iron. PMID- 1312859 TI - Kinetic and spectroscopic analysis of the inactivating effects of nitric oxide on the individual components of Azotobacter vinelandii nitrogenase. AB - The effects of nitric oxide (NO) on the individual components of Azotobacter vinelandii nitrogenase have been examined by kinetic and spectroscopic methods. Incubation of the Fe protein (Av2) for 1 h with stoichiometries of 4- and 8-fold molar excesses of NO to Av2 dimer resulted in a complete loss of activity of Av2 in C2H2-reduction assays. The kinetics of inactivation indicated that the minimum stoichiometry of NO to Av2 required to fully inactivate Av2 lies between 1 and 2. The rate of inactivation of Av2 activity by NO was stimulated up to 2-fold by the presence of MgATP and MgADP but was unaffected by the presence of sodium dithionite. Unexpectedly, complete inactivation of Av2 by low ratios of NO to Av2 also resulted in a complete loss of its ability to bind MgATP and MgADP. UV visible spectroscopy indicated that the effect of NO on Av2 involves oxidation of the [4Fe-4S] center. EPR spectroscopy revealed that the loss of activity during inactivation of Av2 by NO correlated with the loss of the S = 1/2 and S = 3/2 signals. Appearance of the classical and intense iron-nitrosyl signal (g = 20.3) was only observed when Av2 was incubated with large molar excesses of NO and the appearance of this signal did not correlate with the loss of Av2 activity. The effects of NO on the MoFe protein (Av1) were more complex than for Av2. A time dependent inactivation of Av1 activity (C2H2 reduction) was observed which required considerably higher concentrations of NO than those required to inactivate Av2 (up to 10 kPa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312860 TI - Retroviral nucleocapsid protein specifically recognizes the base and the ribose of mononucleotides and mononucleotide components. AB - The interaction of the retroviral nucleocapsid protein (NC) with nucleic acids forms the basis of its varied roles in the replication cycle, which include binding and condensing the viral RNA within the virion, stimulation of the early steps in reverse transcription, and dissociation from RNA in the replication complex. As part of an investigation of the NC binding site and of the forces that drive its interaction with nucleic acids, the relative affinities of NC from avian myeloblastosis virus were determined for a series of mononucleotides and mononucleotide components using a competitive displacement assay utilizing the extrinsic fluorescent probe bis-ANS [Secnik, J., Wang, Q., Chang, C.-M., & Jentoft, J.E. (1990) Biochemistry 29, 7991-7997]. The estimated binding affinities were unexpectedly similar for nucleotides, nucleosides, and bases (Ka greater than 10(6) M-1). AMP, UMP, GMP, and CMP bound to NC with essentially equal affinity, indicating that NC does not discriminate between bases. This is consistent with its role in coating, condensing, and packaging the RNA within virions. Nucleosides, bases, riboses, and ribose phosphate bind to NC with 1000 fold higher affinity than inorganic phosphate, indicating that the NC binding site includes elements that recognize nucleotide base and ribose components in addition to phosphate ions. However, the binding affinities of components are not additive, i.e., the Kapp values for adenine and deoxyribose are very similar to that for deoxyadenosine, indicating that the interaction between the NC subsite and the base and the sugar components is complex. The stoichiometry of the complex between bis-ANS and NC was established to be NC.(bis-ANS)3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312861 TI - EPR evidence for nitric oxide production from guanidino nitrogens of L-arginine in animal tissues in vivo. AB - Administration of Fe(2+)-citrate complex (50 mg/kg of FeSO4 or FeCl2 plus 250 mg/kg of sodium citrate) subcutaneously in the thigh or Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) intraperitoneally, (i.p.) to mice induced NO formation in the livers in vivo at the rate of 0.2-0.3 micrograms/g wet tissue per 0.5 h. The NO synthesized was specifically trapped with Fe(2+) diethyldithiocarbamate complex (FeDETC2), formed from endogenous iron and diethyldithiocarbamate (DETC) administered i.p. 0.5 h before decapitation of the animals. NO bound with this trap resulted in the formation of a paramagnetic mononitrosyl iron complex with DETC (NO-FeDETC2), characterized by an EPR signal at g perpendicular = 2.035, g parallel = 2.02 with triplet hyperfine structure (HFS) at g perpendicular. This allowed quantification of the amount of NO formed in the livers. An inhibitor of enzymatic NO synthesis from L-arginine, NG-nitro-L arginine (NNLA, 50 mg/kg) attenuated the NO synthesis in vivo. L-Arginine (500 mg/kg) reversed this effect. Injection of L-[guanidineimino-15N2]arginine combined with Fe(2+)-citrate or LPS led to the formation of the EPR signal of NO FeDETC2 characterized by a doublet HFS at g perpendicular, demonstrating that the NO originates from the guanidino nitrogens of L-arginine in vivo. PMID- 1312862 TI - Voltage-dependent stimulation of Na+/K(+)-pump current by external cations: selectivity of different K+ congeners. AB - Currents generated by the endogenous Na+/K+ pump in the oocytes of Xenopus laevis were determined under voltage-clamp as currents activated by different K+ congeners. The voltage dependence of the pump current reflects voltage-dependent steps in the reaction cycle. The decrease of K(+)-activated pump current at positive potentials has been attributed to voltage-dependent stimulation by the external K+ (Rakowski, Vasilets, LaTona and Schwarz (1991) J. Membr. Biol. 121, 177-187). In Na(+)-free solution, activation of the pump by external cations seems to be the dominating voltage-dependent and rate-determining step in the reaction cycle. Under these conditions, the voltage dependence of apparent Km values for pump activation can be analyzed. The dependence suggests voltage dependent binding of extracellular cations assuming that an effective charge of about 0.4 of an elementary charge is moved in the electrical field during a step associated with the cation binding. The apparent Km values at 0 mV differ for various cations that stimulate pump activity. The values are in mM: 0.10 for Tl+, 0.63 for K+, 0.71 for Rb+, 9.3 for NH4+, and 12.9 for Cs+. The corresponding apparent affinities follow the same sequence as the cation permeability of the K(+)-selective delayed rectifier channel of nerve cells. The results are compatible with the interpretation that the cations have to pass an ion-selective access channel to reach their binding sites in the pump molecule. PMID- 1312864 TI - The role of Mg2+ and K+ in the phosphorylation of Na+,K(+)-ATPase by ATP in the presence of dimethylsulfoxide but in the absence of Na+. AB - We have previously demonstrated that Na+,K(+)-ATPase can be phosphorylated by 100 microM ATP and 5 mM Mg2+ and in the absence of Na+, provided that 40% dimethylsulfoxide (Me2SO) is present. Phosphorylation was stimulated by K+ up to a steady-state level of about 50% of Etot (Barrabin et al. (1990) Biochim. Biophys. Acta 1023, 266-273). Here we describe the time-course of phosphointermediate (EP) formation and of dephosphorylation of EP at concentrations of Mg2+ from 0.1 to 5000 microM and of K+ from 0.01 to 100 mM. The results were simulated by a simplified version of the commonly accepted Albers Post model, i.e. a 3-step reaction scheme with a phosphorylation, a dephosphorylation and an isomerization/deocclusion step. Furthermore it was necessary to include an a priori, Mg(2+)- and K(+)-independent, equilibration between two enzyme forms, only one of which (constituting 14% of Etot) reacted directly with ATP. The role of Mg(2+) was two-fold: At low Mg2+, phosphorylation was stimulated by Mg2+ due to formation of the substrate MgATP, whereas at higher concentrations it acted as an inhibitor at all three steps. The affinity for the inhibitory Mg(2+)-binding was increased several-fold, relative to that in aqueous media, by dimethylsulfoxide. K+ stimulated dephosphorylation at all Mg(2+) concentrations, but at high, inhibitory [Mg2+], K+ also stimulated the phosphorylation reaction, increasing both the rate coefficient and the steady state level of EP. Generally, the presence of Me2SO seems to inhibit the dephosphorylation step, the isomerization/deocclusion step, and to a lesser extent (if at all) the phosphorylation reaction, and we discuss whether this reflects that Me2SO stabilizes occluded conformations of the enzyme even in the absence of monovalent cations. The results confirm and elucidate the stimulating effect of K+ on EP formation from ATP in the absence of Na+, but they leave open the question of the molecular mechanism by which Me2SO, inhibitory Mg2+ and stimulating K+ interact with the Na+,K(+)-ATPase. PMID- 1312863 TI - Pyrophosphate-induced acidification of trans cisternal elements of rat liver Golgi apparatus. AB - Trans cisternal elements of the Golgi apparatus from rat liver, identified by thiamin pyrophosphatase cytochemistry, were isolated by preparative free-flow electrophoresis and were found to undergo acidification as measured by a spectral shift in the absorbance of acridine orange. Acidification was supported not only by adenosine triphosphate (ATP) but nearly to the same degree by inorganic pyrophosphate (PPi). The proton gradients generated by either ATP or PPi were collapsed by addition of a neutral H+/K+ exchanger, nigericin, or the protonophore, carbonyl cyanide m-chlorophenylhydrazone, both at 1.5 microM. Both ATP hydrolysis and ATP-driven proton translocation as well as pyrophosphate hydrolysis and pyrophosphate-driven acidification were stimulated by chloride ions. However, ATP-dependent activities were optimum at pH 6.6, whereas pyrophosphate-dependent activities were optimum at pH 7.6. The Mg2+ optima also were different, being 0.5 mM with ATP and 5 mM with pyrophosphate. With both ATPase and especially pyrophosphatase activity, both by cytochemistry and analysis of free-flow electrophoresis fractions, hydrolysis was more evenly distributed across the Golgi apparatus stack than was either ATP- or PPi-induced inward transport of protons. Proton transport colocalized more closely with thiamin pyrophosphatase activity than did either pyrophosphatase or ATPase activity. ATP- and pyrophosphatase-dependent acidification were maximal in different electrophoretic fractions consistent with the operation of two distinct proton translocation activities, one driven by ATP and one driven by pyrophosphate. PMID- 1312865 TI - Synthetic lipid-anchored receptors based on the binding site of a monoclonal antibody. AB - Highly specific ligand receptor interactions generally characterize molecular recognition at cell surfaces and other biological systems. In this study we simulate a membrane receptor by fusing a monoclonal antibody fragment to a phospholipid. A sulfhydryl group in the hinge region of a monoclonal antibody fragment, was covalently linked to derivatives of phosphatidylethanolamines and phosphatidylserine via three different hydrophilic spacer arms. We investigated and characterized these lipid-anchored Fab-fragments which we have named 'Fab lipids' in liposomal and monolayer systems. Methods for the monomolecular assembling of such films at the air/water interface and techniques used for their manipulation are outlined. We describe two possibilities for building a monomolecular receptor layer, consisting of two-dimensional pattern of oriented Fab-fragments with their artificial hydrophobic anchor embedded in a lipid matrix. In the first method a monomolecular film at the air/water interface was allowed to form from a vesicular suspension and driven into a phase separation, resulting in protein rich domains embedded in a protein depleted phase. This film was transferred onto a solid support in such a way that the established pattern was preserved. Alternatively, a recognition pattern was formed by directly cross linking the Fab-fragments to preformed planar membranes composed of the reactive spacer-lipids and an inert matrix lipid. Specificity as well as contrast of the binding activity of the receptor layers were qualified using micro-fluorimetry. PMID- 1312866 TI - Transport mechanisms in chloride channels. PMID- 1312867 TI - Transforming growth factors-beta as regulators of cellular growth and phenotype. AB - An increasing number of cDNAs and polypeptides have been ascribed to the transforming growth factor-beta (TGF-beta) superfamily. It has become evident that this evolutionally well-conserved gene family has representatives in many organisms, from invertebrates to mammalians. As new members are being identified, the knowledge of their biological significance is derived not only from studies of their effects in various in vitro models, but also of their organismal expression during different stages of embryogenesis and morphogenesis. The major described functions of the TGF-beta and like proteins seem to be the regulation of cell proliferation, phenotype, and differentiation. Part of these effects may be attributed to changes in the adhesive properties of the cells and integrity of their extracellular matrices modulated by TGF-beta. Identification of the new members of the TGF-beta family, their biological effects, cell-surface receptors, and cell or tissue-specific expression will be invaluable in trying to understand the purpose of many seemingly alike multiregulators. PMID- 1312868 TI - Antisense inhibition of oncogene expression. AB - To understand the role of individual genes in regulating biological processes, one must be able to interfere specifically with either their expression or function. While monoclonal antibodies have proven very useful in studying cell surface proteins, the specific inhibition of intracellular proteins in viable cells is a much more difficult problem. The goal of antisense technology is to develop small oligonucleotides, plasmids, or retroviral vectors which can be readily introduced into living cells in order to inhibit specific gene expression. In this review, we briefly describe the principles of antisense usage, including problems of cellular uptake and intracellular distribution, mechanism of antisense action, and the properties of various oligonucleotide derivatives. In addition we present several examples of the biological effects of antisense administration used to study the role of specific genes in the regulation of cell growth and differentiation. PMID- 1312870 TI - Characterization of TNF receptors. PMID- 1312869 TI - Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions. AB - Hepatocyte growth factor (HGF) is the most potent mitogen for mature hepatocytes and seems to act as a hepatotropic factor that has not been purified over the past 30 years. HGF was first purified from rat platelets in 1986. HGF is a hetrodimer molecule composed of 69-kDa alpha-subunit and 34-beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and primary structure of HGF was determined. HGF is derived from preproprecursor of of 728 amino acids, which is proteolytically processed to form mature HGF. The alpha-chain contains four kringle domains and it has 38% homology with plasmin. HGF mRNA and HGF activity increase markedly in the liver of rats after various liver injuries such as hepatitis, ischemia, physical crush, and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells and sinusoidal endothelial cells, but not in parenchymal hepatocytes. HGF mRNA is also markedly increased even in the intact lung, kidney, and spleen after injuries of the liver. Therefore, HGF may act as a trigger for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, HGF mRNA increases markedly in the kidney after various renal injuries, thus it suggests that HGF may act not only as a hepatotropic factor but also as a renotropic factor. HGF receptor with a Kd of 20 to 30 pM is widely distributed in various epithelial cells including hepatocytes. HGF receptor was recently identified as the product of c-met protooncogene, which encodes a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF has recently been shown to be a pleiotropic factor. HGF stimulates growth of various epithelial cells, including renal tubular cells (Mitogen). It is worth noting that HGF strongly enhances motility of epithelial cells (Motogen) and induces epithelial tubule formation (Morphogen), while it strongly inhibits growth of several tumor cells. All these findings indicate that HGF may have important roles in organogenesis, morphogenesis, carcinogenesis, as well as in organ regeneration. PMID- 1312871 TI - Purification and structural properties of two distinct TNF receptors on human cells. PMID- 1312873 TI - Natural inhibitors of TNF. PMID- 1312872 TI - TNF signal transduction and TNF-responsive genes. PMID- 1312874 TI - Antiproliferative and antitumor activity of TNF in vitro and in vivo. PMID- 1312875 TI - The parameter identification problem for the somatic shunt model. AB - The somatic shunt model, a generalized version of the Rall equivalent cylinder model, is used commonly to describe the passive electrotonic properties of neurons. Procedures for determining the parameters of the somatic shunt model that best describe a given neuron typically rely on the response of the cell to a small step of hyperpolarizing current injected by an intrasomatic recording electrode. In this study it is shown that the problem of estimating model parameters for the somatic shunt model using physiological data is ill-posed, in that very small errors in measured data can lead to large and unpredictable errors in parameter estimates. If the somatic shunt is assumed to be a real property of the intact neuron, the effects of these errors are not severe when predicting EPSP waveshapes resulting from synaptic input at a given location. However, if the somatic shunt is assumed to be a consequence of a leakage pathway around the recording electrode, and a correction for the shunt is applied, then the instability of the inverse problem can introduce large errors in estimates of EPSP waveshape as a function of synaptic location in the intact cell. Morphological constraints can be used to improve the accuracy of the inversion procedure in terms of both parameter estimates and predicted EPSP responses. PMID- 1312877 TI - Mediastinal germ cell tumors. AB - Mediastinal germ cell tumors are among the most common tumors in the anterior mediastinum. This tumor should be considered strongly in the differential diagnosis of anterior mediastinal masses. Benign teratomas are common in this site, and complete surgical resection results in cure of nearly all patients. Malignant mediastinal seminomas are highly curable and either radiotherapy (mediastinal disease) or cisplatin-based chemotherapy (metastatic disease) will result in long-term survival in 80% or more of patients. Mediastinal nonseminomatous germ cell malignancies represent a clinically and biologically distinct subset of mediastinal germ cell neoplasms. Relative to their testicular counterparts, these tumors carry a poor prognosis, but, with newer refinements in cisplatin-based chemotherapy, approximately half of these patients will survive their illness. The history of success with chemotherapy should prompt thorough pathologic and serologic evaluation of all patients with mediastinal malignancies in hopes of defining a curable process. In particular, poorly differentiated carcinomas at this site should be treated as germ cell tumors, and so long-term survival will be attainable. Mediastinal nonseminomatous germ cell tumors are associated with the development of nongerm cell malignancies such as embryonal rhabdomyosarcomas and hematologic malignancies such as acute megakaryocytic leukemia and malignant histiocytosis. The development of these associated malignancies is not related to therapy and represents a true biological link between these malignancies. It is likely that the development of these malignancies is an expression of the multipotential nature of primitive germ cells. Careful clinical and biologic investigations of these rare transformations may lead to greater understanding of the regulation of events in the malignant process. PMID- 1312876 TI - Mediastinal masses: diagnosis with noninvasive techniques. PMID- 1312878 TI - Mediastinal germ cell tumors: the role of surgery. PMID- 1312879 TI - [The diagnosis of lymphatic vascular dysplasia and lymphatic fistula formation]. AB - The importance of lymphangiography for diagnosing the formation of lymphatic fistulas and vascular dysplasias of the lymphatic vessels is on the increase within the scope of therapeutic invasiveness. Its importance and ranking in diagnosing lymphatic circular disorders is demonstrated and exemplified by case reports on three patients suffering from chylothorax of various origin, on one patient with chyluria, and one patient with lymphoedema in the soft parts of the neck. In two chylothorax patients, lymphangiography resulted in successful surgery. It is the decisive method in diagnosis and therapy planning in fistulas and dysplasias of the lymphatic vessel system. PMID- 1312882 TI - Advances in solid-phase red cell adherence methods and transfusion serology. PMID- 1312880 TI - cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. AB - To determine how the human cdc25 gene product acts to regulate p34cdc2 at the G2 to M transition, we have overproduced the full-length protein (cdc25Hs) as well as several deletion mutants in bacteria as glutathione-S-transferase fusion proteins. The wild-type cdc25Hs gene product was synthesized as an 80-kDa fusion protein (p80GST-cdc25) and was judged to be functional by several criteria: recombinant p80GST-cdc25 induced meiotic maturation of Xenopus oocytes in the presence of cycloheximide; p80GST-cdc25 activated histone H1 kinase activity upon addition to extracts prepared from Xenopus oocytes; p80GST-cdc25 activated p34cdc2/cyclin B complexes (prematuration promoting factor) in immune complex kinase assays performed in vitro; p80GST-cdc25 stimulated the tyrosine dephosphorylation of p34cdc2/cyclin complexes isolated from Xenopus oocyte extracts as well as from overproducing insect cells; and p80GST-cdc25 hydrolyzed p-nitrophenylphosphate. In addition, deletion analysis defined a functional domain residing within the carboxy-terminus of the cdc25Hs protein. Taken together, these results suggest that the cdc25Hs protein is itself a phosphatase and that it may function directly in the tyrosine dephosphorylation and activation of p34cdc2 at the G2 to M transition. PMID- 1312881 TI - Synthetic alpha-thrombin receptor peptides activate G protein-coupled signaling pathways but are unable to induce mitogenesis. AB - alpha-Thrombin (thrombin) stimulates phospholipase C and modulates the activity of adenylate cyclase in a number of cell types via G protein-coupled receptors. It is also a potent growth factor, notably for a line of hamster fibroblasts (CCL39 cells). Recently, predicted amino acid sequences for human and hamster thrombin receptors have been reported that display a putative thrombin cleavage site in the N-terminal extracellular domain. Synthetic peptides corresponding to 14 residues carboxyl to the presumed thrombin cleavage site of the human receptor have been shown to activate platelets as well as the thrombin receptor expressed in Xenopus oocytes. In the present study we have examined the effects of synthetic peptides corresponding to the same region of the hamster receptor (S-42 L-55) and shorter peptides (2-7 residues) on signal transducing systems in CCL39 cells. Our results indicate that hamster receptor peptides of greater than or equal to 5 residues effectively stimulate phospholipase C in CCL39 cells via the thrombin receptor and induce rapid desensitization of the response. The same peptides also inhibit adenylate cyclase in a pertussis toxin-sensitive manner. Although the peptides are potent agonists of serotonin release in platelets, unlike thrombin, by themselves they are not mitogenic. However, they potentiate DNA synthesis in cooperation with growth factors possessing tyrosine kinase receptors. Hence, we conclude that the potent mitogenic action of thrombin cannot be accounted for solely by the activation of the cloned receptor. We postulate the existence of an additional receptor activated by thrombin, which is required for its full mitogenic potential. PMID- 1312883 TI - Effect of dibutyryl cyclic adenosine 3',5'-monophosphate on morphological features and biological markers of human salivary myoepithelial cell line in culture. AB - We have found the emergence of myoepithelial cells (HSG-AZA1) in neoplastic human salivary intercalated duct cell line HSG in culture after treatment with 5 azacytidine. When HSG-ZAZ1 cells were cultured in the presence of N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dB-cAMP), they formed long cytoplasmic processes which were densely packed with ample microfibrils in addition to microtubule bundles. The expression of neuron-specific enolase, synaptophysin, and catecholamine as well as neurofilaments in the treated HSG-AZA1 cells was found by the immunofluorescence staining technique, immunoblotting, immunoelectron microscopy, or catecholamine fluorescence. Both the anchorage independent and anchorage-dependent growths of HSG-AZA1 cells were suppressed in the presence of dB-cAMP. After the removal of dB-cAMP from the culture, the treated cells returned rapidly to the phenotype and growth rate of the untreated cells. These findings indicate that reversible differentiation into the neuron like cells of HSG-AZA1 cells occurs in growth medium containing dB-cAMP. PMID- 1312884 TI - Feline leukemia virus: pathophysiology, prevention, and treatment. PMID- 1312885 TI - Intensive chemotherapy for extensive-stage small-cell lung cancer (SCLC) PMID- 1312886 TI - A pilot study of intensive weekly chemotherapy for extensive disease small-cell lung carcinoma. AB - An intensive weekly chemotherapeutic treatment for extensive disease small-cell lung cancer was piloted in 14 patients. The regimen consisted of 6 drugs. Two drugs were given each week for a total of 12 weeks of treatment. Modifications were required in the protocol to attempt to overcome excessive toxicity. Unexpected toxicity included anemia requiring transfusions in 8 of 10 patients completing treatment, sepsis in 8 of 14 with 3 related deaths, and prolonged grade III motor neurotoxicity in 2 patients. All 3 patients who died of sepsis had shown evidence of response, and 8 of the remaining 11 had 90% or greater tumor shrinkage. Two others had a partial response. Median survival time for all patients was 9.3 months. PMID- 1312887 TI - Potassium channel activators and bronchial asthma. AB - The cromakalim-like KCOs relax airways smooth muscle by an action that is associated with the opening of plasmalemmal K(+)-channels. The K(+)-channel involved may be analogous to the ATP-sensitive K(+)-channel identified in pancreatic beta-cells. It is unlikely to be open under normal circumstances and plays little role in determining the strong outward rectifying behaviour of the plasmalemma of the airways smooth muscle cell. K(+)-channel opening may cause relaxation of the airways smooth muscle cell by mechanisms additional to inhibition of Ca2+ influx through L-type VOCs. The cromakalim-like KCOs have bronchodilator activity in vivo and can depress NANC excitatory neuroeffector transmission in the lung at concentrations smaller than those required to relax airways smooth muscle. The mechanism of action of cromakalim in alleviating nocturnal asthma may not involve direct relaxation of airways smooth muscle. It is possible that cromakalim may instead act to inhibit the mechanisms underlying airway hyper-reactivity. PMID- 1312889 TI - Signet ring cell carcinoma of the stomach. AB - Between 1965 and 1985, 51 of 1500 patients (3.4%) with gastric cancer who had gastric resection had signet ring cell gastric cancer. Patients with this form of cancer tended to be younger and female; the tumors were smaller and involved the stomach body, serosal invasion was less prominent, and lymph node metastases were less likely to be present. Early mucosal and submucosal cancer was present in 54.9% of the patients with the signet ring cell and in 24.6% with other types of gastric cancer. In 15.7% of patients with signet ring cell cancer, a noncurative resection was performed. The 5-year survival rate was 74.5% for patients with signet ring cell cancer and 52.4% for those with other types of gastric cancer (P less than 0.01). In patients with signet ring cell gastric cancer, the lesion is less extensive; thus, these patients probably can expect a longer survival time. PMID- 1312888 TI - Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients. AB - Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects. PMID- 1312890 TI - Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (KMBC). AB - A new human extrahepatic bile duct carcinoma cell line (KMBC) was established from a serially transplanted tumor in nude mice that originated from a surgically resected tumor from a 73-year-old Japanese man; the cell line has been maintained for 5 five years. KMBC cells proliferate in a monolayered sheet with a population doubling time of 30 hours. Chromosome number was distributed in a range from 37 to 44, with modal numbers of 40 and 41. KMBC cells and the reconstituted tumor in a nude mouse showed moderately to poorly differentiated adenocarcinoma and possessed various functional characteristics of extrahepatic bile duct carcinoma. KMBC cells secreted carbohydrate antigen 19-9, tissue polypeptide antigen, carcinoembryonic antigen, ferritin, beta 2-microglobulin, fibronectin, and alpha 2-macroglobulin and produced glutamic oxaloacetic transaminase and alkaline phosphatase. KMBC is the second established cell line that originated from a human extrahepatic bile duct carcinoma in the world literature, and it will be applicable to various experiments. PMID- 1312891 TI - Superoxide anion-generating activity of polymorphonuclear leukocytes and monocytes in patients with lung cancer. AB - Superoxide anion (O2-) production by polymorphonuclear leukocytes (PMN) and monocytes (MN) was measured in the peripheral blood of 70 patients with lung cancer. The O2- production by these cells was decreased in many, but not all, patients. The incidence of patients with lower O2- production increased as the stage advanced. The correlation between O2- production by these cells and peripheral blood smears was evaluated in patients with cancer. Patients with 80% granulocytes and 40% monocytes or more in their peripheral blood had a significantly lower O2- production by PMN and MN compared with those with less than 80% granulocytes and 40% monocytes, respectively. These results indicate that an abnormally increased number of granulocytes and monocytes in the peripheral blood of patients with cancer may depress immunoregulatory function. In addition, decreased O2- production by these cells should be considered when assessing the defense mechanisms and susceptibility to infection of these patients. PMID- 1312892 TI - Argyrophilic nucleolar organizer regions in breast carcinoma. Correlation with DNA flow cytometry, histopathology, and lymph node status. AB - Argyrophilic nucleolar organizer regions (AgNOR) have been correlated with proliferative activity of neoplasms. Increased AgNOR may reflect increased proliferative activity of cells or ploidy. To explore this hypothesis, 41 breast carcinomas were processed for AgNOR silver staining and DNA flow cytometry. AgNOR counts were expressed as mean AgNOR/nucleus and percentage of tumor cells with more than five AgNOR/nucleus. The first count was designated mean AgNOR or mAgNOR, and the second count was designated AgNOR proliferative index or pAgNOR. Using Mantel-Haensel statistical analysis, carcinomas that exhibited mAgNOR of 2.4 or more had a high likelihood of aneuploidy (P less than 0.0001), an S-phase fraction of more than 5.8% (P less than 0.003), or a diameter greater than 2 cm (P less than 0.007). In addition, tumors with pAgNOR of 8% or more showed a statistically significant correlation with aneuploidy (P less than 0.004), tumor grade (P less than 0.04), and a more significant one with high S-phase fraction (P less than 0.0001). No significant correlation was obtained between pAgNOR and tumor size or lymph node status. These data indicate that AgNOR quantitation reflects changes in DNA ploidy and cell proliferation. They also suggest that the mean AgNOR counts correlate best with the DNA mass or ploidy and that the frequency of cells with higher AgNOR count best reflects proliferative activity or S-phase fraction. PMID- 1312893 TI - Two cell lines established from mixed mullerian tumors of the uterus. Morphologic, immunocytochemical, and cytogenetic analyses. AB - To clarify the cellular origin and characteristics of malignant mixed mullerian tumor (MMMT), the authors investigated two cell lines (designated as FU-MMT-1 and FU-MMT-2) established from two patients with heterologous MMMT of the uterus. Both cell lines propagated continuously for 83 and 55 serial passages over 1.5 years, respectively. Morphologically, FU-MMT-2 was a mixture of carcinoma cells and sarcoma cells with predominance of carcinoma cells; FU-MMT-1 only had a sarcomatous element with distinct rhabdomyoblastic differentiation. Immunocytochemically, the sarcoma cells of each cell line expressed, not only myogenic and mesenchymal antigens (desmin, myoglobin, and vimentin), but also epithelial antigens, including epithelial membrane antigen and keratin. The carcinoma cells in FU-MMT-2 were positive for the epithelial antigens and vimentin and negative for desmin and myoglobin. Both lines had abnormal karyotypes; the modal chromosome numbers of FU-MMT-1 and FU-MMT-2 were 47 and 80, respectively. In addition, FU-MMT-1 had trisomy 8, and FU-MMT-2 had complex structural abnormalities. When transplanted into nude mice, FU-MMT-1 reproduced and maintained the characteristics of the original tumor. These cell lines and xenografts appear to provide a useful system for studying the biologic behavior, cytogenetic features, and histogenesis of MMMT. In conclusion, the presence of epithelial antigens in the sarcomatous and carcinomatous elements seemed to support the hypothesis that both elements are derived from a common stem cell. PMID- 1312894 TI - Cytogenetic findings in three primary hepatocellular carcinomas. AB - Short-term cultures of three primary hepatocellular carcinomas were cytogenetically analyzed. Case 1 displayed a normal karyotype. Case 2 had, in addition to cells with a normal male chromosome complement, a clone with -Y. In case 3, two abnormal clones were found, one with -Y and one with a highly aberrant karyotype: [formula: see text] Our results, collated with the findings in one previously published primary hepatocellular carcinoma and in three cell lines, suggest that structural changes of chromosomes 1 and 6, leading to loss of 1p and 6q material, and loss of chromosome 16 are frequent events in hepatocellular carcinogenesis. PMID- 1312895 TI - Multidrug sensitivity phenotype of human lung cancer cells associated with topoisomerase II expression. AB - Patterns of drug sensitivities in relation to topoisomerase II gene expression and activity were studied in eight human lung cancer cell lines not selected in vitro for drug resistance. The cytotoxicities of doxorubicin, etoposide, teniposide, cisplatin, camptothecin, and 5-fluorouracil were measured and, remarkably, these unselected cell lines were shown to have a common pattern of multidrug sensitivity, i.e., a multidrug sensitivity phenotype. In fact, drug sensitivities were significantly correlated with each other in the studied cell lines, the correlation being best for the topoisomerase II-targeted agents and cisplatin, less strong with camptothecin, and weak with 5-fluorouracil. Almost 1 log range difference of topoisomerase II gene expression was found in these cell lines, and this was not explained by the cell-doubling time or cell cycle distribution. The level of topoisomerase II gene expression was positively and highly correlated with the cell sensitivity to epipodophyllotoxins, doxorubicin, and cisplatin in seven cell lines. Although weaker, an association was also observed between topoisomerase II gene expression and camptothecin cytotoxicity, while no association was observed with 5-fluorouracil. However, a non-small cell lung cancer cell line with neuroendocrine properties had very low levels of expression of the topoisomerase II gene, despite being highly sensitive to all drugs tested. The levels of topoisomerase I gene expression were not found to be correlated with the cytotoxicity of any drug tested. A specific enzymatic activity assay and a teniposide-stimulated DNA cleavage assay showed that the extent of active topoisomerase II present in nuclear extracts paralleled the level of topoisomerase II gene expression. Furthermore, in addition to the normal transcript, an abnormally sized topoisomerase II message and a rearrangement of the topoisomerase II gene were detected in a poorly sensitive small cell lung cancer cell line. Therefore, low levels of topoisomerase II gene expression, and possibly mutations, may predict a reduced sensitivity of unselected human lung cancer cell lines to several drugs, including agents with a cellular target other than topoisomerase II. It is hypothesized that topoisomerase II might be involved in a common pathway of cell death induced by drugs in tumor cell lines which present a multidrug sensitivity phenotype. PMID- 1312896 TI - p53 mutations in human lung tumors. AB - Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in the mutational hot spots (exons 4-8) of p53 in DNA samples from 40 lung cancers. Most (31 of 40) samples were preselected for LOH in the region of p53. We detected 23 p53 mutations within these exons in 22 lung cancers; no p53 mutations were found in normal tissue of the patients. One-half of the mutations were G to T transversions on the nontranscribed strand, consistent with mutagenesis by tobacco smoke. Mutations of C to A on the nontranscribed strand, which would result from G to T mutations on the transcribed strand, were detected only in one sample. Three of 23 mutations were nonsense mutations; to date, nonsense mutations of p53 have not been reported in lung cancer. Mutation of this p53 coding region was detected in 20 of 27 small cell lung cancer samples, representing a 70% occurrence. Mutation of the p53 gene is apparently very frequent in small cell lung cancers. When LOH in the p53 region could be determined, complete concordance occurred between a sample having both a p53 mutation and LOH in the region of p53 (18 of 18 samples). Twelve samples of lung cancer had LOH in the region of p53, but the samples had no detectable p53 mutations, suggesting either alterations outside the known mutational hot spots of p53 or alterations of another unidentified tumor suppressor gene in the region of p53. PMID- 1312897 TI - Establishment and characterization of an in vitro model of acquired resistance to cisplatin in a human testicular nonseminomatous germ cell line. AB - Clinically, human testicular nonseminomatous germ cell tumors exhibit remarkable sensitivity to platinum-based chemotherapy. To define better the mechanistic basis for this unusual sensitivity, the biochemical determinants of platinum induced cytotoxicity have been investigated in a human testicular tumor cell line (GCT27) established from a previously untreated patient and in an in vitro derived 5.6-fold cisplatin-resistant stable variant (GCT27cisR). Compared to 12 ovarian and 5 cervical human tumor cell lines, the parent GCT27 line was among the most sensitive to the cytotoxic effects of both cisplatin (dosage producing 50% inhibition, 0.2 microM) and carboplatin (dosage producing 50% inhibition, 2.9 microM), thus reflecting clinical data. A 4-day exposure sulforhodamine B staining assay was used to determine that GCT27cisR was cross-resistant to carboplatin and iproplatin and the classical bifunctional alkylating agents melphalan and chlorambucil. Partial cross-resistance was observed to tetraplatin, methotrexate, and mitomycin C. No cross-resistance was observed to Adriamycin, etoposide, vinblastine, bleomycin, 1-beta-D-arabinofuranosylcytosine, and 5 fluorouracil. Intracellular cisplatin accumulation across the dose range 2.5-100 microM (for 2 h) was 1.6 +/- 0.39-fold (mean +/- SD) greater for the parent line. There was no significant difference in glutathione levels between the two lines. The acquired resistance line was 1.9-fold more resistant than the parent line to the cytotoxic effects of cadmium chloride. There was no significant difference between the two lines, however, in the total amounts of platinum bound to DNA after cisplatin exposure (25, 50, or 100 microM for 2 h). The removal of total platinum adducts from DNA was significantly faster for GCT27cisR compared to the parent line (half-times of removal, 32 and 67 h, respectively). These data suggest that the abnormal sensitivity of the parent testicular tumor cell line to platinum-containing anticancer drugs may be due predominantly to an inherent defect in the ability of these cells to remove platinum from their DNA. This defect is apparently lost in the acquired resistance counterpart. Reduced intracellular accumulation and increased cytoplasmic concentrations of metallothionein may also contribute, in part, to the acquisition of cisplatin resistance in this model. PMID- 1312898 TI - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human lung and liver microsomes and cytochromes P-450 expressed in hepatoma cells. AB - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen in animals, has been linked to tobacco-related cancers in humans. The cytochrome(s) P-450 (P-450) responsible for the metabolic activation of NNK in humans has not been identified. The present work investigated the ability of human lung and liver microsomes and 12 forms of human P-450, expressed in Hep G2 (hepatoma) cells, to metabolize NNK. Of the 12 P-450 forms, P-450 1A2 had the highest activity in catalyzing the conversion of NNK to the keto alcohol, 4 hydroxy-1-(3-pyridyl)-1-butanone. P-450s 2A6, 2B7, 2E1, 2F1, and 3A5 also had measurable activities in the formation of keto alcohol. The apparent Km and Vmax for the formation of keto alcohol in the P-450 1A2-expressed Hep G2 cell lysate were 309 microM and 55 pmol/min/mg protein, respectively. 4-(Methylnitrosamino)-1 (3-pyridyl)-1-butanol, a reductive product, was the major metabolite formed, whereas the formation of keto alcohol and its aldehyde and acid derivatives (all alpha-hydroxylation products) constituted approximately 1% of the initial amount of NNK in P450-expressed Hep G2 cell lysate. A similar metabolite pattern was observed with human lung or liver microsomes. In human lung microsomes, the apparent Kms for the formation of 4-hydroxy-4-(3-pyridyl)butyric acid, 4-oxo-1-(3 pyridyl)-1-butanone, NNK-N-oxide, and 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanol were 526, 653, 531, and 573 microM, respectively; the formation of keto alcohol was not observed. For human lung microsomes, there was no sex-related difference in NNK metabolism. Carbon monoxide (90% atmosphere) significantly inhibited the metabolism of NNK in human lung and liver microsomes. 7,8 Benzoflavone, an inhibitor of P-450s 1A1 and 1A2, had no effect on NNK metabolism in human lung microsomes but decreased the formation of keto alcohol by 47% in human liver microsomes. Similarly, antibodies against human P-450s 1A2 and 2E1 decreased keto alcohol formation by 42% and 53%, respectively, in human liver microsomes but did not affect NNK metabolism in lung microsomes. Inhibitory antibodies against P-450s 2A1, 2C8, 2D1, or 3A4 had little or no effect on the metabolism of NNK in human liver or lung microsomes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1312899 TI - Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases. AB - Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases. PMID- 1312900 TI - The involvement of active DNA synthesis in camptothecin-induced G2 arrest: altered regulation of p34cdc2/cyclin B. AB - Cell cycle arrest in G2 phase is a common response to a variety of DNA-damaging agents. The coupling between DNA damage and G2 arrest was studied in synchronized HeLa cells using camptothecin, a highly specific inhibitor of topoisomerase I that damages DNA through the formation of reversible topoisomerase I-DNA cleavable complexes. Brief camptothecin treatment of early S-phase HeLa cells caused arrest at G2 phase and abolished the activation of p34cdc2 protein kinase. Both tyrosine dephosphorylation of p34cdc2 and cyclin B accumulation were altered. These cell cycle-dependent changes were not observed when DNA replication was inhibited by aphidicolin during the brief camptothecin treatment. Our results suggest that to produce G2 arrest, active DNA synthesis is required at the time of camptothecin treatment, as was previously shown for camptothecin induced cytotoxicity. Furthermore, our results suggest that the interaction of the replication fork with DNA damage may ultimately trigger altered regulation of p34cdc2/cyclin B, leading to cell cycle arrest at the G2 phase. PMID- 1312901 TI - Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the insulin like growth factor II autocrine growth loop. AB - Suramin is a polysulfonated naphthyl-urea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10(-4) and 9 x 10(-5) M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using 125I-IGF-I and found that suramin displaced 125I-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach. PMID- 1312902 TI - Topoisomerase I alteration in a camptothecin-resistant cell line derived from Chinese hamster DC3F cells in culture. AB - Camptothecin-resistant DC3F Chinese hamster lung fibroblast cell lines were obtained after mutagenic treatment with ethylmethanesulfonate and subsequent exposure to 1 microM camptothecin (CPT). The most resistant cell line, which was obtained after exposure to CPT for 10 days, was designated DC3F/C-10. Comparison of 50% inhibitory concentration values after 8-h CPT treatments showed that DC3F/C-10 cells were 134-fold resistant to CPT. Resistance was associated with marked reduction of CPT-induced DNA single-strand breaks and DNA-protein cross links. This reduction was not due to reduced amounts of immunoreactive DNA topoisomerase I protein, although nuclear extracts from DC3F/C-10 cells had less enzyme catalytic activity than those from DC3F cells. Also, fast protein liquid chromatography-purified DNA topoisomerase I from DC3F/C-10 had lower specific catalytic activity than that from DC3F cells. DNA topoisomerase I from DC3F/C-10 was resistant to inhibition of catalytic activity and induction of DNA cleavage by CPT. These results suggest that CPT resistance in DC3F/C-10 cells is due to qualitative alteration of DNA topoisomerase I. PMID- 1312903 TI - Inhibitors of polyamine biosynthesis block tumor necrosis factor-induced activation of macrophages. AB - The activation of polyamine biosynthesis, dependent on increased gene expression of ornithine decarboxylase, has been found to play an important role in the control of cell proliferation and differentiation. In this report it has been found that accumulation of ornithine decarboxylase mRNA also follows stimulation of human monocytes/macrophages by tumor necrosis factor. Human recombinant tumor necrosis factor (100 units/ml) also evoked an enhanced respiratory burst of macrophages. The respiratory burst response was inhibited in a dose-dependent manner with difluoromethylornithine, an inhibitor of ornithine decarboxylase, and methylglyoxal-bis(guanylhydrazone), an inhibitor of the formation of spermidine and spermine. The data presented in this paper suggest that polyamines may play a functional role in tumor necrosis factor-driven macrophage activation, and they are discussed in the context of their possible use as inhibitors of polyamine metabolism in tumor chemotherapy. PMID- 1312904 TI - Endocrine aspects of benign breast disease. AB - The purpose of this study was to determine the levels of dehydroepiandrosterone sulfate (DHAS) in the plasma of women with benign breast disease (BBD) and in normal subjects. Possible changes in DHAS plasma levels and in its adrenal secretion under adrenocorticotrophin hormone (ACTH) were also investigated in women with BBD before and after bromocriptine therapy. Our results demonstrate that plasma levels of DHAS in women with BBD overlap with those found in controls. Prolactin (PRL) suppression in women with BBD receiving bromocriptine treatment was associated with a significant (p less than 0.02) decrease of baseline DHAS plasma levels and of stimulated ACTH response curve (p less than 0.02). These data suggest a possible relationship between PRL and DHAS secretion in women with BBD. PMID- 1312905 TI - Human hepatocyte growth factor stimulates the growth of HUH-6 clone 5 human hepatoblastoma cells. AB - The effects of human hepatocyte growth factor (hHGF), a potent mitogen for rat and human hepatocytes in primary culture, on proliferation of human hepatoma and hepatoblastoma cells were examined. Out of five cell lines; HLE, HuH-6 clone 5, HuH-7, PLC/PRF/5, and Hep G2, only HuH-6 Clone 5 cells were stimulated by recombinant hHGF. Both native and recombinant hHGFs caused dose-dependent increases in cell number and DNA synthesis of cells. This stimulation was strongly inhibited by anti-hHGF monoclonal antibody. PMID- 1312906 TI - Penetration of etoposide into human malignant brain tumors after intravenous and oral administration. AB - Penetration of etoposide into the cerebrospinal fluid, brain tumor, and brain tissue after intravenous administration was investigated in patients presenting with malignant brain tumors. A relatively low dose (55-65 mg/m2) was used to compare intravenous with oral administration. High-performance liquid chromatography with fluorescence detection was used to evaluate drug levels. Plasma and cerebrospinal fluid levels of etoposide after oral administration (50 150 mg/day) were also studied so as to determine the adequate oral dose for the treatment of malignant brain tumors. The peak plasma concentration after intravenous administration ranged from 7.01 to 10.47 micrograms/ml, varying in proportion to the injected dose, whereas that after oral administration was lower, namely, 1.44-4.99 micrograms/ml, and was unstable when the oral dose was 150 mg daily. The peak cerebrospinal fluid level following either intravenous or oral administration was much lower than the plasma concentration and was influenced by the peak plasma level and the sampling site. The etoposide concentration in cerebrospinal fluid taken from the subarachnoid space and ventricle of patients displaying no tumor invasion and of those presenting with meningeal carcinomatosis and in cerebrospinal fluid taken from the dead space after tumor resection was 0.7% +/- 0.5%, 3.4% +/- 1.0%, and 7.2% +/- 8.5%, respectively, of the plasma concentration. Serial oral administration did not result in the accumulation of etoposide in cerebrospinal fluid. The tumor concentration (1.04-4.80 micrograms/g) was 14.0% +/- 2.9% of the plasma level after intravenous administration, was related to the injected dose, and was approximately twice the concentration detected in the brain tissue. Therefore, a relatively low dose of etoposide injected intravenously penetrates the brain tumor at an efficacious concentration. Our results indicate than an oral dose of 100 mg etoposide be given for malignant brain tumors, as limited penetration of the drug into the intracranial region was observed. PMID- 1312907 TI - Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin. AB - The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients. PMID- 1312908 TI - Treatment of inoperable hepatocellular carcinoma by intra-arterial lipiodol and 4'-epidoxorubicin. AB - A total of 30 patients presenting with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial Lipiodol (5 ml) and 4'-epidoxorubicin (90 mg/m2) once every 4 weeks. The treatment results included no complete response, 2 partial responses, 6 cases of static disease and 19 cases of progressive disease. The median survival was 18.9 weeks. All patients had died by the time of this writing, with survival duration ranging from 4.1 to 87.3 weeks. Toxicities were minimal and included anaemia and alopecia. As compared with a historic control group that had received the same dose of intravenous 4'-epidoxorubicin, the treatment group showed similar response rates but developed fewer toxicities. There was no significant survival benefit over the control group. We concluded that although this form of treatment had comparable activity and produced fewer side effects, it provided no survival benefit over intravenous treatment. The slight prolongation of survival achieved in the treatment group as compared with the control arm might have been due to case selection. PMID- 1312909 TI - Phase II study of ACNU as second-line treatment in small-cell lung cancer. EORTC Lung Cancer Cooperative Group. AB - A total of 24 patients presenting with small-cell lung cancer either resistant to or relapsing within 3 months after first-line treatment were entered in a phase II study of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU). ACNU was given i.v. at a dose of 75 mg/m2 every 6 weeks. We observed a partial response of 7 months' duration in one patient and one case of stable disease that lasted for 6 months; all other subjects exhibited progressive disease. Two patients developed brain metastases during treatment. The toxicity of ACNU consisted mainly of bone marrow suppression, especially thrombocytopenia. At this dose and on this schedule, ACNU shows minimal activity as second-line treatment in small-cell lung cancer. PMID- 1312910 TI - Beta-adrenergic receptors and catecholamines in the rat heart during tourniquet trauma. AB - Tourniquet trauma produced a decrease in the noradrenaline content in the heart of the rats through the period of tourniquet application (up to 4 hr). In the same period, the content of adrenaline was significantly increased. This relationship between noradrenaline and adrenaline remained the same in the posttraumatic period. Parallel to the observed changes in the catecholamine content of the heart, a significant decrease in the number of the beta-adrenergic receptors (Bmax) and an increase in their affinity (a decrease in KD) was also found in the hearts of rats exposed to tourniquet trauma. These changes remained throughout the posttraumatic period, with one exception: no change 30 min after trauma has been observed. Reapplication of tourniquet was associated with a restoration of the beta-adrenergic receptors and complete survival of the animals. The decrease in the beta-receptors density after trauma might be due to down-regulation produced by increased concentration of adrenaline, a beta receptor agonist. Meanwhile, some other factors, particularly ischaemia, might also contribute to the observed changes in the beta-adrenergic binding sites. PMID- 1312911 TI - Effect of alpha-adrenergic stimulation on activation of protein kinase C and phosphorylation of proteins in intact rabbit hearts. AB - The intracellular events and specifically the role of protein kinase C-mediated protein phosphorylation, after alpha-adrenergic receptor stimulation of the heart, are not well understood. We examined the phosphorylation of sarcolemmal, sarcoplasmic reticular, myofibrillar, and cytosolic proteins in perfused beating rabbit hearts on activation of protein kinase C by phenylephrine. Perfusion of rabbit hearts with phenylephrine was associated with a positive inotropic response, which was dose and time dependent. Maximal stimulation (1.54-fold increase in +dP/dt) was obtained with 10 microM phenylephrine at 4 minutes. Examination of the activity levels of protein kinase C in these hearts revealed a redistribution of this activity from the cytosolic to the membranous fraction, suggesting the activation of this enzyme in vivo. Prazosin, an alpha 1-adrenergic antagonist, prevented the increase in the inotropy and the redistribution of protein kinase C activity mediated by phenylephrine. Examination of the degree of phosphorylation of membranous, myofibrillar, and cytosolic proteins revealed that activation of protein kinase C in vivo was associated with increased phosphorylation of a 15-kd sarcolemmal protein and a 28-kd cytosolic protein. There were no increases in the degree of phosphorylation of phospholamban in the sarcoplasmic reticulum and of troponin I, troponin T, and C protein in the myofibrils, although these proteins were found to be substrates for protein kinase C in vitro. These findings provide evidence that protein kinase C is activated in response to alpha-adrenergic stimulation and that activation is associated with increased phosphorylation of a 15-kd sarcolemmal protein and a 28 kd cytosolic protein in the myocardium. PMID- 1312912 TI - Existence of both fast and slow channel activity during the early stages of ventricular fibrillation. AB - Although sodium channels have been reported to be inactive after 5-10 minutes of ventricular fibrillation (VF), their state during early VF is unknown. In 12 open chest dogs, a floating glass microelectrode was used to record intracellular action potentials from the right ventricle during pacing and during electrically induced VF. Before any drug was administered, an initial episode of VF was continuously recorded for at least 20 seconds followed by defibrillation. Recordings were made during VF episodes after superfusion for 15 minutes around the microelectrode site by low (2.8 x 10(-5) M) and high (10(-4) M) concentrations of tetrodotoxin (TTX) in five dogs, or by low (4 microM) and high (100 microM) concentrations of verapamil in another four dogs. In three dogs, VF was induced without drugs three times to determine if the effects observed in the previous dogs were caused by the drugs or by successive episodes of VF. Ten consecutive action potentials were analyzed at the onset and after 5, 10, 15, and 20 seconds of VF. Action potential amplitude and duration during paced rhythm or VF were not changed by the local perfusion of either TTX or verapamil. In the TTX group, the maximum upstroke rate of depolarization of an action potential (Vmax) during paced rhythm was 104 +/- 14 V/sec for control cycles before any drug was given, 86 +/- 15 V/sec for the low TTX concentration, and 55 +/- 14 V/sec for the high TTX concentration (p less than 0.05 versus other two). Vmax decreased from 55 +/- 32 V/sec at the beginning of VF to 37 +/- 27 V/sec after 20 seconds of VF for predrug VF, from 39 +/- 20 V/sec to 18 +/- 11 V/sec for low-dose TTX VF, and from 18 +/- 13 V/sec to 12 +/- 7 V/sec for high-dose TTX VF (p less than 0.05 among the three groups). In the dogs receiving verapamil, VF was still inducible with Vmax not significantly different from predrug VF at the onset and after 5 or 20 seconds of VF but with Vmax smaller (p less than 0.05) for verapamil than for predrug VF after 10 or 15 seconds of VF. In three dogs, Vmax was not significantly different during three successive episodes of VF when no drug was given between the episodes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1312913 TI - Beta-adrenergic modulation of fast inward sodium current in canine myocardium. Syncytial preparations versus isolated myocytes. AB - Reports have suggested that the fast inward sodium current (INa) in cardiac tissues may be modulated by beta-adrenergic stimulation and that such modulation may affect conduction in the setting of myocardial ischemia and infarction. However, many of these studies have used dissociated myocytes or broken cell preparations, whose responses need not necessarily reflect those of syncytial preparations. To investigate further the possibility that beta-adrenergic stimulation of INa may differ in various preparations, we compared the effects of the beta-agonist isoproterenol (ISO) on syncytial canine Purkinje fibers and ventricular muscle preparations, as well as isolated ventricular myocytes. Alterations of the maximum rate of rise of the action potential upstroke (Vmax) were used as an index of changes of INa. ISO (1 microM) had no effect on Vmax of upstrokes of normally polarized (fast responses) or partially depolarized (elevated [K+]o, depressed fast responses) syncytial ventricular muscle preparations or Purkinje fibers. In contrast, lower concentrations of ISO (0.5 1.0 microM) modulated Vmax of isolated ventricular myocytes, depending on the technique used to monitor transmembrane potential. When 2.7 M KCl-filled microelectrodes were used, ISO reduced Vmax of partially depolarized myocytes without affecting Vmax of normally polarized myocytes. However, when myocytes were dialyzed using patch pipettes, ISO reduced Vmax of partially depolarized myocytes and increased Vmax of normally polarized myocytes, effecting a hyperpolarized shift of the normalized inactivation curve relating Vmax to resting membrane potential. The different beta-adrenergic responses of syncytial preparations and nondialyzed and dialyzed myocytes suggest that differences in the ionic or metabolic condition of the preparations likely alter cAMP-dependent responses and channel phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312914 TI - Development of the main efferent cells of the olfactory bulb and of the bulbar component of the anterior commissure. AB - The development of the efferent cells of the main olfactory bulb and the development of the bulbar part of the anterior commissure were studied in the rat from E16 to P7. DiI was used in fixed tissues as a neuronal tracer. From E16 onwards cells located in the olfactory bulb anlage were stained in a Golgi-like appearance. The morphological changes of these cells were: from E16 to P4, re orientation from a tangential position to a radial position, elongation of the principal dendrite and spreading out of the secondary dendrites. From P4 onwards, there was a lack of migrating mitral cells in the inner part of the bulb. At E16 some fibers of the anterior commissure reached the midline, the number of fibers increased slowly until P0/P1. At P2 there was an explosive increase in the number of fibers crossing the midline and reaching the contralateral bulb. The development in two stages is hypothesized. PMID- 1312915 TI - Ontogenic development of the TTX-sensitive and TTX-insensitive Na+ channels in neurons of the rat dorsal root ganglia. AB - Developmental changes in the sensitivity of neurons to tetrodotoxin (TTX) were studied in relation to the cell size in rat dorsal root ganglia (DRG). Na+ currents were recorded from neurons of various stages of development. Two types of Na+ channels were identified on the basis of their sensitivity to TTX. One type was insensitive to a very high concentration (0.1 mM) of TTX, while the other type was blocked by a low concentration (1 nM) of TTX. These two types of Na+ channels were observed throughout the developmental stages examined from day 17 of gestation and adulthood. Thus, both types of Na+ channels are already established at the early stage of neuronal development and appear to be retained throughout the life-span of the DRG neuron. The concentration-response relationships for the block of TTX-sensitive Na+ current by TTX did not appreciably change during development. Although two types of Na+ channels had strikingly different kinetic properties, the kinetic properties of each channel type were basically similar throughout development. The TTX-sensitive Na+ channels were mainly concentrated in cells with large cell diameters throughout developmental stages examined. These large cells appear to correspond to the 'large-light' cells. On the contrary, the TTX-insensitive Na+ channels were found in smaller diameter cells which may correspond to the 'small-dark' cells. Thus, it is concluded that there are heterogeneous categories of neurons which have Na+ channels with different physiological and pharmacological properties. Since Na+ channels play a pivotal role in the action potential generation, these heterogeneity of DRG neurons appear to be instrumental in integrating the sensory signals. PMID- 1312916 TI - A rapid assay for the measurement of Na+,K(+)-ATPase inhibitors. AB - A rapid and automated assay for inhibitors of Na+, K(+)-ATPase was developed by determining the amount of inorganic phosphorus (Pi) released by Na+,K(+)-ATPase in a centrifugal analyzer. This method avoids long incubation, strong acids and centrifugation as in the conventional manual method. The coefficients of variation of intra- and inter-assay at ouabain concentration 0.5 mumol/L were 1.0 and 1.4%, respectively. The method is quick, reproducible and easy compared with current techniques. PMID- 1312918 TI - Cytomegalovirus detection in kidney transplants: results obtained from the polymerase chain reaction. AB - Kidneys from twelve renal transplant recipients were examined prior to and after graft failure and explantation. The investigations included conventional light and electron microscopy and the analysis of human cytomegalovirus-related viral proteins and viral DNA. Nucleic acid hybridization studies were conducted on kidney explants by an in situ method using DNA probes and by the polymerase chain reaction employing primers and probe for immediate early gene targets. In none of the cases did light and electron microscopy including immunohistochemistry for human cytomegalovirus reveal active infection in punch biopsies or explants. Interestingly, in situ hybridization also failed to detect human cytomegalovirus even in two cases with seroconversion, while the polymerase chain reaction was positive. The polymerase chain reaction disclosed only two additional positive cases within the residual group of explanted kidneys. In our hands, the polymerase chain reaction was the only potent direct detection method for cytomegalovirus in transplanted human kidneys. PMID- 1312917 TI - Diabetes mellitus induces red blood cell plasma membrane alterations possibly affecting the aging process. AB - Various alterations of red blood cell (RBC) plasma membrane appear both in diabetes mellitus and during the physiological aging process. Diabetes mellitus decreases RBC life-span; therefore, it may change the plasma membrane by acting through its effect on the aging process. In order to clarify the issue, RBCs from normal subjects and insulin-dependent diabetic patients were fractionated in five subpopulations of different mean age (fraction 1: early young RBC, fraction 5: mature RBC). Thereafter, plasma membranes were prepared and enzymatic activities, membrane fluidity and lipid peroxidation were evaluated. NA+, K(+)-ATPase activity decreased during aging and it was higher in all RBC subpopulations from normal subjects in comparison to diabetic patients. Next, lipid peroxidation and fluidity increased during aging in both the study groups; in this case, however, in all subpopulations, except for that from fraction 1, RBCs from diabetic patients showed higher membrane fluidity and lipid peroxidation in comparison to normal subjects. Data herein reported suggest that diabetes mellitus affects the plasma membrane independently of (lipid peroxidation and fluidity) or dependently on (Na+, K(+)-ATPase) its effect on aging. In the case of lipid peroxidation and fluidity diabetes mellitus seems to affect the membrane by decreasing RBC life span, whereas in the case of Na+K(+)-ATPase it seems to alter this enzymatic activity which in turn might affect RBC aging. Acetylcholinesterase activity decreased during aging in RBCs from normal subjects, but it increased in RBCs from diabetic patients; RBC subpopulation from fraction 1, on the other hand, showed similar values in normal subjects and diabetic patients. In this case the effect of diabetes mellitus appears only during aging. PMID- 1312919 TI - Anti-hepatitis C virus antibodies in primary Sjogren's syndrome: false positive results are related to hyper-gamma-globulinaemia. PMID- 1312920 TI - ASHP therapeutic guidelines for intravenous immune globulin. ASHP Commission on Therapeutics. PMID- 1312921 TI - Clarithromycin and azithromycin: new macrolide antibiotics. AB - The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described. Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin. Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis. Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii. Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms. Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis. The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing. Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures. Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis. Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome. The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain. Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA. Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation. PMID- 1312922 TI - Two macrolide antimicrobials approved for marketing. PMID- 1312923 TI - Three cases of posttransfusion hepatitis C treated with interferon-alpha. Confirmation of a carrier state by detection of hepatitis C virus RNA after interferon therapy. AB - Interferon therapy is useful for decreasing the serum ALT level and improving liver histology in patients with chronic non-A, non-B hepatitis. This study examined the effect of interferon therapy in acute cases of posttransfusion hepatitis C. We report on three cases in which interferon alpha was administered at 100-220.5 million units. HCV RNA became undetectable during interferon administration and the ALT level declined to the normal range. However, after the cessation of the therapy, the ALT level began to fluctuate and HCV RNA reappeared in two patients. We concluded that interferon therapy for the acute phase of posttransfusion hepatitis is useful for suppressing viral replication and quickly improving the ALT level, but it can not always prevent the development of chronic hepatitis. Furthermore, there was a close correlation between the profile of HCV RNA and that of the ALT level, indicating that the replication of HCV plays an important role in liver injury. PMID- 1312924 TI - Accuracy of bronchial aspiration cytology in typing operable (stage I-II) pulmonary carcinomas. AB - The accuracy of bronchial aspiration cytology in typing resectable (stage I-II) lung cancer has been investigated in 100 cases, comparing preoperative cytologic features with pulmonary tumor histology seen at surgery. The accuracy has been 100% for small-cell carcinoma (two cases), 98.8% for squamous-cell carcinoma (86 cases), and 91.6% for adenocarcinoma (12 cases). The overall accuracy rate has been 98%. No case of undifferentiated large-cell carcinoma has been identified. It is suggested that the high accuracy in cytologic typing of operable lung cancer is basically related to adequate preservation of differentiation features, thus allowing for correct identification of most non-small-cell carcinoma. Moreover, the absence in this study of any large-cell carcinoma, compared with its frequency in advanced stage series, would indicate that such a histotype reflects excessive dedifferentiation of an original squamous or glandular form. PMID- 1312925 TI - Cervicovaginal cytology in carcinosarcoma [malignant mixed mullerian (mesodermal) tumor] of the uterus. AB - We examined the cervicovaginal cytology (PAP) findings in a series of 21 endometrial and 2 cervical carcinosarcomas (CS) [malignant mixed mullerian (mesodermal) tumors] (MMMT). Initial cytology diagnosis was positive for cancer in 14 of 23 cases (sensitivity of 61%); however, CS was correctly identified only 2 times. The remaining 12 cancer diagnoses were carcinomas: 10 adenocarcinomas (4 endometrial, 1 cervical, and 5 adenocarcinomas not otherwise specified), 1 squamous carcinoma, and 1 poorly differentiated carcinoma. Seventeen smears were available for review, all 8 false negative, one unsatisfactory, and 8 of 14 true positive smears. One false negative smear showed rare clusters diagnostic of adenocarcinoma. The remaining 7 false negative smears showed 3 high grade squamous dysplasias (two with additional findings: one showed atypical spindle cells and the other showed endometrial stromal cells), 2 extensive repair changes, and 2 negatives. The unsatisfactory smear showed atypical spindle cells. Review of the 8 true positive smears confirmed malignant spindle cells in the two cases originally identified as CS by cytology and in 3 other cases originally identified as adenocarcinoma. Of 9 smears positive for cancer available for review, 4 showed only carcinoma cells. PAP positive for cancer was associated with high stage at presentation (P less than .025) and recurrent disease (P less than .001) (even among stage I or II patients, P less than .025). PAP positive for cancer showed no association with depth of myometrial invasion, size, grade, or histologic type of carcinosarcoma. The results of this study demonstrate the importance of consultative cytology reporting in which recommendations for appropriate biopsy are included in the report.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312926 TI - Comparison of immunocytochemistry and in situ hybridization in the cytodiagnosis of genital herpetic infection. AB - Over a 62-month period, 53 patients were found to have cervicovaginal smears that contained cells consistent with, or equivocal cells for, a herpes simplex virus (HSV) infection. The Papanicolaou-destained smears from these cases were restrained in situ hybridization (ISH) with a biotinylated cloned DNA probe and immunocytochemistry (ICC) assay and were compared for the detection of HSV in cervicovaginal smears by two methods. Cytological findings classified the 53 slides into two groups, i.e., cytologically herpes positive (33 patients) and equivocal cases (20 patients). Each group was subdivided into two groups: group A was confirmed by ICC, and group B was confirmed by ISH technique. Of the 33 cellular samples containing cells considered to be consistent with a herpes infection, 15 (88%) of 17 were positive by means of ICC technique (group A), 6 (43%) of 14 were positive by ISH technique (group B). Of the 20 smears showing equivocal cell changes thought unlikely to be caused by an HSV infection, 6 (60%) of 10 were positive by ICC (group A), 2 (29%) of 7 were positive by ISH (group B). With the ISH technique, five smears showed dislodged cells from glass slides due to enzyme treatment and denaturation. The results revealed that the ICC technique is a rapid and reliable procedure and thus recommended for routine diagnosis of HSV infection. Moreover, ICC is easier to perform and interpret and is less expensive than ISH. Therefore, the ICC may be preferable to ISH for detecting HSV in routine Papanicolaou diagnostic work. PMID- 1312927 TI - Neonatal herpes simplex virus infection diagnosed by cytology of tracheobronchial aspirates. PMID- 1312928 TI - The primary structure and gene organization of human substance P and neuromedin K receptors. AB - The gene organization and amino acid sequences of human substance P and neuromedin K receptors (SPR and NKR, respectively) are reported on the basis of molecular cloning and sequence determination of genomic DNA containing the respective receptor gene. The human SPR and NKR genes, unlike many other genes for G-protein-coupled receptors, (G protein, guanyl-nucleotide-binding-regulatory protein), contain introns which interrupt the protein-coding regions into 5 exons. The human SPR and NKR genes extend over 60 kb and 45 kb, respectively and are considerably larger than the human substance K receptor (SKR) gene consisting of 12 kb. All 4 introns, however, are located at equivalent positions of the three tachykinin receptor genes, suggesting that they evolved from a common ancestral gene. Human SPR and NKR consist of 407 and 465 amino acid residues, respectively, each possessing structural features characteristic of the members of G-protein-coupled receptors. The human and rat receptors show a common tendency of distinctly segmented sequence conservation and divergence among the three receptors, and the observed sequence conservation and divergence would contribute to the emergence of similar but distinct properties of the three receptors. Furthermore, the amino acid sequences and the gene sizes are more closely related between SPR and NKR than between SKR and NKR, suggesting that the SPR gene evolved from the primordial NKR gene after a gene duplication to form the NKR and SKR genes. PMID- 1312929 TI - Target size analysis of prostaglandin endoperoxide synthase. Radiation inactivation of both cyclooxygenase and peroxidase correlated with the monomer of 72 kDa. AB - To determine the size of the functional catalytic unit of prostaglandin endoperoxide (prostaglandin H) synthase, radiation inactivation experiments were performed. Both microsomes from ovine seminal vesicles and purified enzyme were irradiated with 10 MeV electrons. The enzymic activities of prostaglandin H synthase, cyclooxygenase and peroxidase, showed mono-exponential inactivation curves dependent on radiation dose, indicating molecular masses of approximately 72 kDa. The enzyme in microsomes, in its native environment, as well as in its purified state after solubilisation with nonionic detergent showed identical molecular masses. The results clearly demonstrate that the monomer of the enzyme with an apparent molecular mass of 72 kDa (SDS/PAGE) is the functional unit for catalysis of both activities. Hence the two active sites of cyclooxygenase and peroxidase reside on the same polypeptide chain. PMID- 1312930 TI - Effect of KCl on the interactions between NADPH:cytochrome P-450 reductase and either cytochrome c, cytochrome b5 or cytochrome P-450 in octyl glucoside micelles. AB - Significant dissociation of FMN from NADPH:cytochrome P-450 reductase resulted in loss of the activity for reduction of cytochrome b5 as well as cytochrome c and cytochrome P-450. However, the ability to reduce these electron acceptors was greatly restored upon incubation of FMN-depleted enzyme with added FMN. The reductions of cytochrome c and detergent-solubilized cytochrome b5 by NADPH:cytochrome P-450 reductase were greatly increased in the presence of high concentrations of KCl, although the stimulatory effect of the salt on cytochrome P-450 reduction was less significant. No apparent effect of superoxide dismutase could be seen on the rate or extent of cytochrome reduction in solutions containing high-salt concentrations. Complex formation of the flavoprotein with cytochrome c, which is known to be involved in the mechanism of non-physiological electron transfer, caused a perturbation in the absorption spectrum in the Soret band region of cytochrome c, and its magnitude was enhanced by addition of KCl. Similarly, an appreciable increase in ellipticity in the Soret band of cytochrome c was observed upon binding with the flavoprotein. However, only small changes were found in absorption and circular dichroism spectra for the complex of NADPH:cytochrome P-450 reductase with either cytochrome b5 or cytochrome P-450. It is suggested that the high-salt concentration allows closer contact between the heme and flavin prosthetic groups through hydrophobic-hydrophobic interactions rather than electrostatic-charge pairing between the flavoprotein and the cytochrome which causes a faster rate of electron transfer. Neither alterations in the chemical shift nor in the line width of the bound FMN and FAD phosphate resonances were observed upon complex formation of NADPH:cytochrome P 450 reductase with the cytochrome. PMID- 1312931 TI - Purification of bovine brain inositol-1,4,5-trisphosphate 5-phosphatase. AB - In bovine brain, two soluble inositol-1,4,5-trisphosphate (InsP3) 5-phosphatases, which catalyse the dephosphorylation of InsP3 to inositol 1,4-bisphosphate, have been separated by DEAE-Sephacel. Type I, i.e. the first eluted enzyme, is the main soluble form and is reminiscent of the membrane-bound enzyme by multiple criteria. Type I was purified to apparent homogeneity by a method involving chromatography on DEAE-Sephacel, Blue-Sepharose, Sephacryl S-200, phosphocellulose, and C18 HPLC. A single protein band of 42-43 kDa was identified by SDS/PAGE, corresponding to the peak of maximal activity. InsP3 5-phosphatase was purified to apparent homogeneity to a final yield of 45-50 micrograms protein. The minimal estimate value of the Vmax for InsP3 5-phosphatase was in the range 20-35 mumol.min-1.mg protein-1. PMID- 1312932 TI - Identification of a high-affinity binding protein for a hepta-beta-glucoside phytoalexin elicitor in soybean. AB - A putative receptor protein for a hepta-beta-glucoside phytoalexin elicitor was identified by photoaffinity labeling of detergent-solubilized proteins from soybean root membranes. Incubation of partially purified beta-glucan-binding proteins with a photolabile 125I-labeled 2-(4-azidophenyl)ethyl-amino conjugate of the heptaglucoside elicitor, followed by irradiation with ultraviolet light (366 nm) resulted in specific labeling of a 70-kDa band in SDS/PAGE. Half-maximal inhibition of the 125I-labeling of the protein band by underivatized hepta-beta glucoside was achieved by 15 nM heptaglucoside. Analysis of the affinity of radiolabel incorporation into the protein by ligand-saturation experiments, gave an apparent Kd value of 3 nM, in full agreement with the results from radioligand binding studies. Good correlation was also observed between the amount of radiolabel incorporated into the protein and the binding activity of the fractions obtained at different stages in the purification of heptaglucoside binding activity. Photoaffinity labeling of proteins purified by glucan-affinity chromatography showed the 70-kDa band as the main component along with weak 125I labeling of a 100-kDa band. The 70-kDa band was also the major protein visualized by silver staining after SDS/PAGE of this fraction, suggesting that it is the predominant form of the heptaglucoside-binding proteins in detergent-solubilized soybean membranes. PMID- 1312933 TI - NMR and EPR studies on a monoheme cytochrome c550 isolated from Bacillus halodenitrificans. AB - A c-type monoheme ferricytochrome c550 (9.6 kDa) was isolated from cells of Bacillus halodenitrificans sp.nov., grown anaerobically as a denitrifier. The visible absorption spectrum indicates the presence of a band at 695 nm characteristic of heme-methionine coordination. The midpoint redox potential was determined at several pH values by visible spectroscopy. The redox potential at pH 7.6 is 138 mV. When studied by 1H-NMR spectroscopy as a function of pH, the spectrum shows a pH dependence with pKa values of 6.0 and 11.0. According to these pKa values, three forms designated as I, II and III can be attributed to cytochrome c550. The first pKa is probably associated with protonation of the propionate groups. The second pKa value introduces a larger effect in the 1H-NMR spectrum and is probably due to the ionisation of the axial histidine. Studies of temperature variation of the 1H-NMR spectra for both the ferrous and ferri forms of the cytochrome were performed. Heme meso protons, the heme methyl groups, the thioether protons, two protons from a propionate and the methylene protons from the axial methionine were identified in the reduced form. The heme methyl resonances of the ferri form were also assigned. EPR spectroscopy was also used to probe the ferric heme environment. A signal at gmax approximately 3.5 at pH 7.5 was observed indicating an almost axial heme environment. At higher pH values the signal at gmax approximately 3.5 converts mainly to a signal at g approximately 2.96. The pKa associated with this change is around 11.3. The N terminal sequence of this cytochrome was determined and compared with known amino acid sequences of other cytochromes. PMID- 1312934 TI - Recombinant human retinoic acid receptor alpha. Binding of DNA and synthetic retinoids to the protein expressed in Escherichia coli. AB - The human retinoic acid receptor alpha was expressed in Escherichia coli. The recombinant protein was found to be very unstable in several E. coli strains, probably due to proteolysis. Conditions were established to obtain reasonable amounts of active protein for ligand and DNA binding studies. The recombinant receptor showed the expected DNA binding activities in gel-retardation assays. Ligand binding properties were measured in a charcoal absorption assay. The dissociation constant for highly specific bound retinoic acid was found to be 0.67 nM. The affinity of several synthetic retinoids to the recombinant protein was determined and compared to their biological activity. Some of the values presented here differ significantly from those published earlier for the receptor or its isolated hormone-binding domain. PMID- 1312935 TI - Inhibition of N-acetylglucosamine kinase and N-acetylmannosamine kinase by 3-O methyl-N-acetyl-D-glucosamine in vitro. AB - During the search for inhibitors of N-acetylneuraminic acid biosynthesis, it was shown that 3-O-methyl-N-acetylglucosamine competitively inhibits the N acetylglucosamine kinase of rat liver in vitro with a Ki value of 17 microM. N Acetylmannosamine kinase is inhibited non-competitively with a Ki value of 80 microM. In a human hepatoma cell line (HepG2), 3-O-methyl-N-acetyl-D-glucosamine (1 mM) inhibits the incorporation of 14C-N-acetylglucosamine and 14C-N acetylmannosamine into cellular glycoproteins by 88% and 70%, respectively. PMID- 1312936 TI - Subunit interactions of GTP-binding proteins. AB - Fluorescence energy transfer [cf. Forster, T. (1948) Ann. Phys. 6, 55-75] was tested for its suitability to study quantitative interactions of subunits of G0 with each other and these subunits or trimeric G0 with the beta 1-adrenoceptor in detergent micelles or after reconstitution into lipid vesicles [according to Feder, D., Im, M.-J., Klein, H. W., Hekman, M., Holzhofer, A, Dees, C., Levitzki, A., Helmreich, E. J. M. & Pfeuffer, T. (1986) EMBO J. 5, 1509-1514]. For this purpose, alpha 0- and beta gamma-subunits and trimeric G0 purified from bovine brain, the beta gamma-subunits from bovine rod outer segment membranes and the beta 1-adrenoceptor from the turkey erythrocyte were all labelled with either tetramethylrhodamine maleimide or fluorescein isothiocyanate under conditions which leave the labelled proteins functionally intact. In the case of alpha 0- and beta gamma-interactions, specific high-affinity binding interactions (Kd approximately 10 nM) and nonspecific low-affinity binding interactions (Kd approximately 1 microM) could be readily distinguished by comparing fluorescence energy transfer before and after dissociation with 10 microM guanosine 5'-O [gamma-thio]triphosphate and 10 mM MgCl2 where only low-affinity binding interactions remained. Interactions between alpha 0- and beta gamma-subunits from bovine brain or from bovine retinal transducin did not differ much. The beta gamma-subunits from bovine brain were found to bind with high transfer efficiency and comparable affinities to the hormone-activated and the nonactivated beta 1 receptor reconstituted in lipid vesicles: Kd = 100 +/- 20 and 120 +/- 20 nM, respectively; however, beta gamma-subunits from transducin appeared to bind more weakly to the beta 1-adrenoceptor than beta gamma-subunits from bovine brain. Separated purified homologous alpha 0- and beta gamma-subunits from bovine brain interfered mutually with each other in binding to the beta 1-adrenoceptor presumably because they had a greater affinity for each other than for the receptor. These findings attest to the suitability of fluorescence energy transfer for studying protein-protein interactions of G-proteins and G-protein linked receptors. Moreover, they supported the previous finding [Kurstjens, N. P., Frohlich, M., Dees, C., Cantrill, R. C., Hekman, M. & Helmreich, E. J. M. (1991) Eur. J. Biochem. 197, 167-176] that beta gamma-subunits can bind to the nonactivated beta 1-adrenoceptor. PMID- 1312937 TI - Tumor necrosis factor-mediated cell lysis in vitro: relationship to cAMP accumulation and guanine nucleotide-binding proteins. AB - We have investigated the modulation of tumor necrosis factor (TNF)-mediated tumor cell lysis by cAMP. Among a panel of human breast tumor cell lines, MCF7 and MDA MB 231 were shown to be, respectively, sensitive and resistant to TNF-mediated cell lysis in vitro. 125I-labeled TNF-binding experiments demonstrated that both cell lines bind TNF, indicating that the differential sensitivity to TNF was not related to TNF receptor expression. To study the relationship between TNF mediated cell lysis and cAMP accumulation, cAMP measurement was performed following TNF treatment. Our data show that TNF alone did not induce an enhancement of intracellular cAMP accumulation either in the TNF-sensitive or in the TNF-resistant cell line. Experiments in which cells were exposed to forskolin revealed that this cAMP elevating drug was efficient in enhancing the sensitivity to TNF of MCF7 cell line. This potentiating effect of forskolin was maximal for suboptimal concentrations of TNF (10 ng/ml), reaching up to 100% when forskolin was added at 100 microM. However, co-stimulating with forskolin of either MDA MB 231 or a TNF-resistant MCF7 clone (MCF7-R-A1) did not induce any reversal of resistance to TNF. We further assessed the interaction of TNF with transmembrane signalling and the possible involvement of guanine nucleotide-binding proteins (G proteins). Bacterial toxin-catalyzed ADP ribosylation of MCF7 and MDA MB 231 membranes was, therefore, performed. Using cholera toxin, we demonstrate that TNF treatment did not quantitatively alter the activity of stimulatory G-proteins either in MCF7 or MDA MB 231 cell line. In contrast, pertussis toxin-catalyzed ADP ribosylation experiments suggest a functional coupling of TNF receptors to a 40-kDa pertussis toxin-sensitive G-protein in the TNF-sensitive MCF78 cell line but not in the TNF-resistant MDA MB 231 cell line. Taken together, these data indicate that cAMP might play a role in TNF-mediated cell lysis and are in support of the involvement of a pertussis toxin-sensitive G-protein in TNF mediated MCF7 cells lysis. PMID- 1312938 TI - Forskolin effects on slow inward current and phasic tension of frog atrial fibres: modulation by adenosine and phosphodiesterase inhibitors. AB - The effects of forskolin, which is known as a direct activator of adenylate cyclase were studied on the slow inward calcium current (Isi) and phasic tension of frog atrial fibres. Forskolin induced a dose-dependent positive inotropic effect related to an increase in the slow inward calcium current. These effects, which were not reproduced by 1,9-dideoxyforskolin, seemed to result from an activation of adenylate cyclase. The action of forskolin was antagonized by adenosine and potentiated by phosphodiesterase inhibitors with the following order of potency: rolipram greater than theophylline greater than dipyridamole; M & B 22,948 was without influence. This study suggests that adenosine and rolipram might be suitable tools for studying the implication of cAMP in the modulation of contraction in frog atrium. PMID- 1312939 TI - Desensitization of histamine H1 receptor-mediated cyclic GMP production in guinea pig lung. AB - Histamine H1 receptor-mediated production of cGMP in guinea-pig lung tissue becomes rapidly desensitized after previous exposure to histamine. This desensitization is clearly concentration dependent and appears to be homologous. Responses to histamine are also inhibited by previous treatment with phorbol 12,13-dibutyrate. Yet, the time course of the inhibition is considerably slower and the maximal inhibition is significantly less compared to receptor desensitization. Moreover, the effects of the phorbol ester are not confined to H1 receptor responses. Since the effects of receptor desensitization are also not prevented by several protein kinase C inhibitors, the development of homologous H1 receptor desensitization is not dependent upon protein kinase C activation, but is caused by a yet unidentified mechanism. PMID- 1312940 TI - Neuropeptide modulation of muscarinic receptors and function in cerebral cortex of young and senescent rats. AB - The possible influence of several neuropeptides on muscarinic receptor binding and function in fronto-parietal cortex of young and senescent Fischer 344 rats was examined. Low concentrations (100 nM) of cholecystokinin, neurotensin and vasoactive intestinal polypeptide (VIP), added in vitro, enhanced carbachol stimulated phosphoinositide metabolism in cortical miniprisms from both young and senescent rats, while somatostatin was ineffective. Interestingly, the VIP receptor antagonist [d-parachloro-Phe6,Leu17[VIP shifted the dose-response curve for carbachol significantly to the right, indicating inhibition of phosphoinositide hydrolysis. No direct actions of neuropeptides on the number or affinity of [3H]l-quinuclidinyl benzilate binding sites nor on agonist conformation states of the muscarinic receptor were noted in cortex from young animals. The neuropeptide modulation of phosphoinositide metabolism was selective for muscarinic systems, as norepinephrine-stimulated phosphoinositide hydrolysis was not altered. Pretreatment with hemicholinium-3, an inhibitor of high-affinity choline uptake, did not prevent the neuropeptide effects, indicating the interaction was probably postsynaptic. It is possible that pharmacologic manipulation of peptidergic processes could improve cholinergic neurotransmission in brain. PMID- 1312941 TI - Polyamines allosterically modulate [3H]nitrendipine binding to the voltage sensitive calcium channel in rat brain. AB - The effects of polyamines on radioligand binding to the slow voltage-dependent Ca2+ channel were studied using membranes from the rat cerebral cortex. [3H]Diltiazem binding was inhibited by arcaine (IC50 = 55 microM) and, in decreasing order of potency, by agmatine, spermidine, spermine and putrescine. Under control conditions, only spermidine and spermine allosterically inhibited [3H]nitrendipine binding while arcaine, agmatine and putrescine were inactive. Nevertheless, putrescine antagonized the effect of spermine as well as the allosteric effects of diltiazem and verapamil on the binding of [3H]nitrendipine, in a manner analogous to that shown previously for Ca2+. Thus, polyamines may function as endogenous modulators of the voltage-dependent Ca2+ channel. PMID- 1312942 TI - Dose-dependent down-regulation of beta-adrenoceptors by isoproterenol in rat C6 glioma cells. AB - Nano- and micromolar isoproterenol concentrations were compared by studying cyclic AMP, beta-adrenoceptor density and beta 1-adrenoceptor mRNA in rat C6 glioma cells. 1 microM isoproterenol significantly changed all parameters at 15 30 min. The beta 1-antagonist metoprolol attenuated the response. No effects of nanomolar isoproterenol on these early changes were observed, although the density of beta-adrenoceptors was significantly reduced beginning at 12 h. The results indicate a different process for beta-adrenoceptor desensitization in C6 cells following physiologically low agonist concentrations. PMID- 1312943 TI - Demonstration of a neurokinin A receptor subtype in transfected fibroblasts. AB - In competitive radioligand binding assays, the NK2 receptor antagonists [Tyr5,D Trp6,8,9,Arg10]NKA(4-10) (MEN 10207) and [Tyr5,D-Trp6,8,9,Arg10]NKA(3-10) (MEN 10208) had high and low affinity, respectively, in bovine stomach membranes and SKLKB82#3 cells, a murine fibroblast cell line transfected with a cDNA encoding for the bovine NK2 receptor. These antagonists also had different affinities when inhibiting neurokinin A-induced polyphosphoinositide hydrolysis in SKLKB82#3 murine fibroblasts. Thus, the de novo protein expressed by the SKLKB82#3 murine fibroblasts may represent a distinct NK2 receptor subtype. PMID- 1312944 TI - An antipodean perception of the mode of action of glycoprotein hormones. AB - Continuance of vertebrate species and maintenance of metabolism have an absolute requirement for the glycoprotein hormones of the anterior pituitary gland. It is now firmly accepted that the N-glycans of these and the related placental hormone, chorionic gonadotropin, have essential if undefined roles in their mechanism of action. However, recent investigations by Weisshaar and his colleagues on the oligosaccharides of human luteinizing hormone and chorionic gonadotropin, do not support the generally accepted view of carbohydrates in hormone-receptor interactions and a further concept is proposed that invokes negative charges and changes in structured water. PMID- 1312945 TI - In vitro enzyme activation with calbindin-D28k, the vitamin D-dependent 28 kDa calcium binding protein. AB - Purified porcine erythrocyte membrane Ca(2+)-ATPase and 3':5'-cyclic nucleotide phosphodiesterase were stimulated in a dose-dependent, saturable manner with the vitamin D-dependent calcium binding protein from rat kidney, calbindin-D28k (CaBP D28k). The concentration of CaBP-D28k required for half-maximal activation (K0.5 act.) of the Ca(2+)-ATPase was 28 nM compared to 2.2 nM for calmodulin (CaM), with maximal activation equivalent upon addition of either excess CaM or CaBP D28k. 3':5'-Cyclic nucleotide phosphodiesterase (PDE) also showed equivalent maximum saturable activation by calbindin (K0.5 act. = 90 nM) or calmodulin (K0.5 act. = 1.2 nM). CaBP-D28k was shown to effectively compete with CaM-Sepharose for PDE binding. Immunoprecipitation with CaBP-D28k antiserum completely inhibited calbindin-mediated activation of PDE but had no effect on calmodulin's ability to activate PDE. While the physiological significance of these results remains to be established, they do suggest that CaBP-D28k can activate enzymes and may be a regulator of yet to be identified target enzymes in certain tissues. PMID- 1312946 TI - Activation of Na+/Mg2+ antiport in thymocytes by cAMP. AB - Mg2+ efflux from Mg(2+)-loaded rat thymocytes was stimulated by 0.1 mM dibutyryl cAMP (db cAMP). The activation of Mg2+ efflux by db cAMP was more expressed at lower Mg(2+)-loading. cAMP induced only a very small increase in the concentration of intracellular free Mg2+ which cannot explain the activation of Na+/Mg2+ antiport. From these results it was concluded that cAMP increases the affinity of the Na+/Mg2+ antiporter for intracellular Mg2+, probably by phosphorylation. PMID- 1312947 TI - Molecular cloning and primary structure of a protein phosphatase 2C isoform. AB - Complementary DNA encoding the isoform of protein phosphatase 2C, termed PP2C2, has been isolated. The cDNA predicts a protein of 390 amino acid residues with a molecular mass of 42,888 Da. The protein displays 76% identity to the PP2C1 isoform. PMID- 1312948 TI - Bestatin inhibits covalent coupling of [3H]LTA4 to human leukocyte LTA4 hydrolase. AB - The covalent coupling of [3H]LTA4 to human leukocyte LTA4 hydrolase is inhibited in a concentration-dependent fashion by pre-incubation with bestatin. This inhibition correlated with the concentration-dependent inhibition by bestatin of LTB4 and LTB5 synthesis by LTA4 hydrolase. Epibestatin, a diastereomer of bestatin, neither inhibited LTB4 or LTB5 production by LTA4 hydrolase nor prevented the covalent coupling of [3H]LTA4 to the enzyme. In contrast, captopril inhibited both LTB4 synthesis by LTA4 hydrolase and covalent coupling of [3H]LTA4 to the enzyme. PMID- 1312949 TI - Electrochemical titration of the cytochrome hemes in the Rhodopseudomonas viridis reaction center. Cyclic equilibrium titrations yield midpoint potentials without evidence for heme cooperativity. AB - The redox and spectral characteristics of the 4-heme cytochrome c unit of the photochemical reaction center from Rhodopseudomonas viridis were studied by a combination of protein electrochemistry and spectroscopy using an ultra thin layer spectroelectrochemical cell. Quantitative and reversible reduction of the high-potential and the low-potential hemes was performed in cyclic titrations to record the optical difference spectra in the alpha-band region. The titration of the absorbance from the high-potential hemes can be approximated with a sum of 2 Nernst functions with Em = 0.113 V and Em = 0.175 V. The corresponding titration of the absorbance from the low-potential hemes yielded Em = -0.257 V and Em = 0.175 V (all potentials quoted vs. Ag/AgC1/3 M KCl; add 0.208 V for potentials vs. standard hydrogen electrode). The high-potential hemes equilibrate rapidly and titrate identically for oxidative and reductive titrations. Under identical conditions, the low-potential hemes exhibit a hysteresis, thus indicating much slower equilibration with the applied potential. Cyclic titrations with increasing equilibration periods, however, indicate the disappearance of the hysteresis for equilibration periods approximately twice as long as for the high potential hemes. We take this as evidence for a slower internal equilibration, but against a cooperativity of the low-potential hemes as observed for other multi-heme cytochromes. PMID- 1312950 TI - Structural changes in profilin accompany its binding to phosphatidylinositol, 4,5 bisphosphate. AB - The effect on the structure of profilin of phosphatidylinositol 4,5-bisphosphate (PIP2) binding was probed by fluorescence and circular dichroism (CD) spectroscopy. Fluorescence of Trp3 and Trp31 of profilin at 292 nm showed a linear decrease in solution emission at 340 nm as PIP2/profilin was increased from 0 to 80:1, apparently due to a static quenching mechanism involving formation of a nonfluorescent PIP2/profilin complex. CD spectra revealed an increase of up to 3.3-fold in the molar ellpticity at 222 nm for profilin as it binds PIP2, as well as changes in the Cotton effect between 250 and 310 nm. These results are consistent with a possible increase in the alpha-helix content of profilin triggered by the binding of PIP2. PMID- 1312951 TI - Cytochrome oxidase-catalyzed superoxide generation from hydrogen peroxide. AB - Superoxide dismutase is shown to affect spectral changes observed upon cytochrome c oxidase reaction with H2O2, which indicates a possibility of O2- radicals being formed in the reaction. Using DMPO as a spin trap, generation of superoxide radicals from H2O2 in the presence of cytochrome oxidase is directly demonstrated. The process is inhibited by cyanide and is not observed with a heat denatured enzyme pointing to a specific reaction in the oxygen-reducing centre of cytochrome c oxidase. The data support a hypothesis on a catalase cycle catalyzed by cytochrome c oxidase in the presence of excess H2O2 (Vygodina and Konstantinov (1988) Ann. NY Acad. Sci., 550, 124-138): (formula: see text) PMID- 1312952 TI - Intracellular delivery of protein kinase C-alpha or -epsilon isoform-specific antibodies promotes acquisition of a morphologically differentiated phenotype in neuroblastoma cells. AB - The protein kinase C (PKC) family participates in a ubiquitous cell signalling system utilizing increased turnover of phosphoinositides. Because down-regulation of total PKC activity has been implicated in the acquisition of a morphologically differentiated phenotype in SH-SY5Y neuroblastoma cells, we aimed to identify the specific PKC isoforms in this process. Here we report that intracellular delivery of PKC-alpha and -epsilon, but not -beta, -gamma or -delta isoform-specific antibodies is sufficient to induce acquisition of a morphologically differentiated phenotype in SH-SY5Y neuroblastoma cells. PMID- 1312953 TI - The biochemistry of malignant hyperthermia: recent concepts. PMID- 1312954 TI - dUTP pyrophosphatase and uracil-DNA glycosylase in rat liver and hepatomas. AB - 1. The activity of dUTP pyrophosphatase (dUTPase) was similar in rat liver and hepatomas of slow or moderate growth rate but was increased several fold in three rapidly growing hepatomas. 2. There was an approx three-fold increase in the activity of uracil-DNA glycosylase in Morris hepatoma 7800 but there was little change in activity in other hepatomas that were examined. 3. The activities of dUTPase and uracil-DNA glycosylase were not significantly affected by two diets that may be promotional for hepatocarcinogenesis, a high orotate diet and an arginine-deficient diet. PMID- 1312955 TI - Influence of phospholipid environment on the phosphatidylethanolamine: ceramide phosphorylethanolamine transferase activity in rat liver plasma membranes. AB - 1. Plasma membranes were treated with phospholipase A2, phospholipase C or phospholipase D. The phosphatidylethanolamine:ceramide-phosphorylethanolamine transferase was deactivated by phospholipase C treatment, whereas phospholipase A2 and phospholipase D did not affect the enzyme. 2. Incorporation of phosphatidylethanolamine and phosphatidylglycerol into partially delipidated plasma membranes resulted in significant stimulation of the transferase, whereas inclusion of sphingomyelin and phosphatidylserine suppressed the enzyme activity. Our results suggest that phosphatidylserine is a regulator of sphingomyelin level in membranes. 3. The activity of phosphatidylethanolamine:ceramide phosphorylethanolamine transferase was not influenced by the fluidity of its lipid environment. PMID- 1312956 TI - Interaction of a nuclear factor 1-like protein with a cAMP response element binding protein in rat liver. AB - 1. The existence of both cAMP-responsive element binding factor and a nuclear factor 1-like (NF-1-like) protein in nuclear extracts from liver of cAMP-treated rat has been revealed. 2. Binding of these proteins to a DNA fragment containing both elements was cooperative, and 50% binding was achieved with considerably less protein than with a fragment bearing either element alone. 3. Cleavage of the fragment between the two elements abolished the apparent cooperative interaction. 4. Southwestern blot analysis showed that the NF-1-like protein has a molecular weight in the 28-30-kDa range. 5. The NF-1-like binding activity was very stable. PMID- 1312957 TI - Activin receptor mRNA expression in rat testicular cell types. AB - cDNA encoding the extracellular domain of the rat activin receptor was cloned using the polymerase chain reaction (PCR). This cDNA is highly homologous to cDNA encoding the extracellular domain of the mouse activin receptor, whereas at the protein level the extracellular domains of both receptors are identical. Employing this cDNA as a probe in Northern blot analysis, expression of two activin receptor mRNAs (6 kb and 4 kb) was observed, in testes of immature and mature rats. Between day 21 and 28 of postnatal development, a large increase in testicular expression of the 4 kb mRNA was found, suggesting expression of this activin receptor mRNA in germ cells. The 4 kb mRNA was indeed present in isolated pachytene spermatocytes and round spermatids, but was absent in elongating spermatids. Sertoli cells obtained from immature and mature rats expressed both the 6 kb and 4 kb mRNAs, whereas the expression of these mRNAs in Leydig cell preparations was very low. These results may imply that activin has multiple actions in the control of testicular function. PMID- 1312958 TI - Endozepine/diazepam binding inhibitor in adrenocortical and Leydig cell lines: absence of hormonal regulation. AB - One of the many effects which have been attributed to the peptide endozepine/diazepam binding inhibitor (Ep/DBI) is the stimulation of adrenocortical and testicular Leydig cell mitochondrial steroidogenesis. We have used two cell lines (Y-1 mouse adrenal cell tumour and MA-10 mouse Leydig cell tumour), both of which exhibit hormone stimulated steroid production, to investigate the role of Ep/DBI in acute hormone stimulated steroidogenesis. The time course of incorporation of 35S-translabel into Ep/DBI and its turnover rate when the isotope was removed were examined. Cell samples were extracted and separated on Sep-Pak C18 columns and analysed using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis followed by fluorography as well as by direct scintillation counting. This allowed us to estimate the in vivo half-life of Ep/DBI and also to investigate the hormonal dependence of the peptide. Data presented here suggest that (i) Ep/DBI levels are not regulated by trophic hormones in these steroidogenic cell lines, and (ii) that the peptide has a relatively long half-life (greater than 3 h), a finding incompatible with suggestions of it having a rapid turnover. Therefore, it seems unlikely that control of Ep/DBI steroidogenic effects is via hormonal modulation of the peptide levels. PMID- 1312959 TI - Effect of a tyrosine kinase inhibitor, genistein, on the actions of prolactin in cultured mouse mammary tissues. AB - Genistein, an inhibitor of tyrosine kinase, was used to determine the possible role of tyrosine kinase in the prolactin (PRL) stimulation of milk product formation and ornithine decarboxylase (ODC) activation in cultured mouse mammary gland tissue. Genistein (10-200 microM) inhibited in a dose-response fashion the PRL stimulation of casein, lipid and lactose synthesis as well as ODC activation. Genistein, however, did not inhibit the phospholipase C, phorbol myristate acetate or cAMP effects on ODC activation. These results suggest the possible involvement of tyrosine kinase in the mechanism by which PRL expresses its effects in mammary gland tissues. PMID- 1312961 TI - Differential screening of ovarian cDNA libraries detected the expression of the porcine collagenase inhibitor gene in functional corpora lutea. AB - cDNA libraries were constructed from porcine granulosa cells of antral follicles as well as functional corpus luteum, and clones encoding stage-specific genes have been isolated by differential screening. A clone specific to the functional stage of corpus luteum was found to encode the porcine collagenase inhibitor gene and the stage-specific expression in luteinizing tissue was confirmed by Northern blot analysis. The complete open reading frame of the porcine collagenase inhibitor was deduced from the nucleotide sequence, and the localization of the product was examined by immunohistochemical staining as well in pig ovary; the inhibitor was detected in the intercellular space of luteal cells and in the connective tissue around blood vessels in the functional corpus luteum. PMID- 1312960 TI - Platelet-derived growth factor is a potent inhibitor of angiotensin II-induced aldosterone synthesis. AB - Platelet-derived growth factor (PDGF) is a potent mitogen for several cell types. In addition, PDGF has vasoconstrictive action and shares some signal transduction mechanisms with angiotensin II (AII). In the present study, we have examined the effects of PDGF on basal and AII-induced aldosterone synthesis in freshly isolated rat adrenal glomerulosa cells. Recombinant human PDGF-BB caused a dose dependent inhibition of AII-induced aldosterone synthesis being effective at concentrations as low as 10(-12) M. We also investigated possible mechanisms of action of PDGF. We have previously reported that the 12-lipoxygenase (LO) pathway of arachidonic acid plays a key role in AII-induced aldosterone synthesis. We thus examined whether PDGF action is mediated by changes in 12-LO activation. PDGF, at the same doses that blocked AII-induced synthesis also significantly inhibited AII-induced increases in the 12-LO product, 12-hydroxyeicosatetraenoic acid (12-HETE) formation. Further, the addition of 12-HETE completely restored the stimulatory effect of AII during inhibition by PDGF. These results suggest that PDGF could act, at least in part, by inhibition of AII-induced 12-HETE formation. We also examined the role of diacylglycerol (DG) formation since we have previously reported that DG is the source of arachidonic acid for 12-HETE formation. We observed that both AII and PDGF stimulated [3H]arachidonic acid labeled DG formation. However, PDGF did not alter AII-induced DG formation suggesting that PDGF action is not mediated by affecting AII-induced increases in DG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312962 TI - Ca2+/calmodulin-dependent phosphorylation of the 100-kDa protein in chick embryonic muscle cells in culture. AB - The pattern of protein phosphorylation was found to change in differentiating chick embryonic myoblasts in culture. The extent of phosphorylation of 42-, 50-, and 100-kDa proteins increased while that of a 63-kDa protein declined in extracts of myoblasts that had been cultured for increasing periods. Of these, the increase in phosphorylation of the 100-kDa protein occurred most dramatically in extracts of myoblasts in an early stage of differentiation and was specifically inhibited by trifluoperazine (TFP) and other calmodulin (CaM) antagonists including chlorpromazine and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7). Treatment of increasing concentrations of TFP to culture medium also decreased the phosphorylation state of the 100-kDa protein and the degree of myoblast fusion in parallel. In addition, levels of both the kinase activity and the 100-kDa protein but not of CaM appeared to rise in the cells cultured for longer periods. These results suggest that (1) a Ca2+/CaM-dependent protein kinase is responsible for phosphorylation of the 100-kDa protein, (2) the TFP-mediated myoblast fusion block may be associated with the inhibitory effect of the drug against the kinase activity, and (3) the increase in phosphorylation state of the 100-kDa protein during myogenic differentiation is due to the rise in levels of the kinase and its substrate. PMID- 1312963 TI - V4, a gene required for the transition from growth to development in Dictyostelium discoideum. AB - The V4 gene of Dictyostelium discoideum is regulated in a nutrient-dependent manner and is deactivated immediately upon the onset of development. V4 is expressed only during growth, but its expression is not required for growth. We propose that the V4 gene product plays a role in the transition from growth to development. We have tested this hypothesis by antisense mutagenesis. Cells transformed with a V4 antisense construct contained no detectable endogenous V4 mRNA. These cells grew normally, but they failed to aggregate. Under conditions which normally promote development, V4 antisense transformants failed to deactivate vegetative-specific genes. These cells also were unable to induce the expression of the cAMP cell surface receptor, the cyclic nucleic phosphodiesterase, and contact sites A, all of which are normally induced under such conditions. Surprisingly, cells transformed with a V4 sense construct displayed a similar morphological and biochemical phenotype as the antisense cells, whereas cells transformed with the parental vector exhibited a normal biochemical and morphological phenotype. These results demonstrate that expression of the V4 gene during growth is required for the proper initiation of development. PMID- 1312965 TI - Tolbutamide inhibits cAMP-dependent phosphorylation of liver 6-phosphofructo-2 kinase/fructose-2,6-bisphosphatase. AB - The activity of a bifunctional enzyme, liver 6-phosphofructo-2-kinase (PFK 2)/fructose-2,6-bisphosphatase (F-2,6-Pase), which regulates the level of liver fructose-2,6-bisphosphate (F-2,6-P2), the most potent activator of PFK, is modulated by its phosphorylation rate mainly catalyzed by cAMP-dependent protein kinase A (PKA). To elucidate the action mechanism of sulfonylurea on liver F-2,6 P2 production, effects of tolbutamide on PKA-dependent phosphorylation of purified liver PFK-2/F-2,6-Phase protein and on kinase and phosphatase activities of the purified enzyme were examined in vitro. The purified enzyme was phosphorylated in the presence of the catalytic subunit of PKA, and tolbutamide inhibited the enzyme phosphorylation catalyzed by PKA in a dose-dependent manner. By adding the same dosages of tolbutamide used in the phosphorylation experiment, reduced activity of PFK-2 and increased activity of F-2,6-Pase in the presence of PKA were restored to the levels observed in the absence of PKA. On the other hand, carboxytolbutamide, an inactive metabolite of tolbutamide, had little effect on enzyme phosphorylation and activity. Our results indicate that tolbutamide inhibits a phosphorylation of the liver PFK-2/F-2,6-Pase catalyzed by PKA along with an activation of PFK-2 and an inactivation of F-2,6-Pase, leading to liver F-2,6-P2 production. PMID- 1312964 TI - Effect of free fatty acids on insulin receptor binding and tyrosine kinase activity in hepatocytes isolated from lean and obese rats. AB - We demonstrated previously that high physiological concentrations of free fatty acids (FFA) rapidly decrease insulin binding, degradation, and action in isolated rat hepatocytes. In this study, hepatocytes from lean and obese Sprague-Dawley rats (Alab, Stockholm) were preincubated with or without 0.4 mM oleic acid, and the effect on insulin binding and tyrosine kinase activity was measured. In the absence of exogenous FFA, insulin binding was reduced in hepatocytes from obese compared with lean rats (mean +/- SE reduction 44 +/- 7%, n = 8, P less than 0.01). Furthermore, the inhibitory effect of oleic acid added to hepatocytes from lean rats (n = 8; 40 +/- 9%, P less than 0.01) was not seen in cells from obese rats. Treating obese rats with Etomoxir, a carnitine palmitoyl transferase I inhibitor, increased insulin binding to isolated hepatocytes by 41 +/- 13% (n = 5, P less than 0.05). There was no difference in total binding to partially purified insulin receptors from solubilized hepatocytes from lean and obese rats, whether cells were or were not preincubated with oleic acid. Tyrosine kinase activity of partially purified receptors from basal or insulin-stimulated cells was not affected by either obesity, treatment with Etomoxir, or preincubating the cells with oleic acid. Thus, both obesity and elevated ambient FFA levels are associated with impaired insulin cell surface binding to isolated hepatocytes, possibly through an effect of lipid oxidation on the internalization/recycling of the insulin-receptor complex without any perturbation of the receptor tyrosine kinase activity. The data suggest that the reduced insulin binding to hepatocytes from obese rats is due to elevated ambient FFA levels. PMID- 1312966 TI - Lymphadenopathy in sclerosing cholangitis: pitfall in the diagnosis of malignant biliary obstruction. AB - We retrospectively reviewed abdominal computed tomographic (CT) studies from 20 patients with sclerosing cholangitis and found evidence of abdominal lymphadenopathy in 13 patients. Enlargement occurred primarily in areas draining the liver, such as the gastrohepatic ligament or celiac axis (N = 8), the porta hepatis (N = 7), and the pancreaticoduodenal region (N = 2). One patient had reactive adenopathy and retroperitoneal fibrosis. The presence of benign reactive lymphadenopathy in at least one intraabdominal location was confirmed by pathological examination of excised lymph nodes in seven patients. Malignancy was excluded by surgical exploration or clinical follow-up. We conclude that enlarged lymph nodes are a common finding by CT in patients with sclerosing cholangitis. Enlarged reactive lymph nodes in this condition should not be mistaken for evidence of periportal metastasis or cholangiocarcinoma. PMID- 1312967 TI - Parenchymal changes of the liver in cholangiocarcinoma: CT evaluation. AB - We evaluated parenchymal changes of the liver in 92 patients (41 peripheral types and 51 hilar types) with cholangiocarcinomas studied by bolus-enhanced computed tomography (CT). In 39% of patients with the peripheral type, a wedge-shaped increased enhancement of the liver was observed peripheral to the tumor on bolus enhanced CT. Tumor was observed in all cases. In 58.8% of patients with the hilar type, a segmental or lobar increased degree of enhancement of the liver was observed, but the tumor was demonstrated in only 58.8%. Atrophy was accompanied by areas of increased enhancement in 80% of hilar type and 25% of peripheral type. Areas of increased degree of enhancement corresponded to a wedged-shaped perfusion defect on CT during arterial portography. On magnetic resonance imaging (MRI), those lesions showed hyperintensity on T2-weighted images. Most of these changes were considered to be due to reversible hepatic parenchymal ischemia secondary to portal vein invasion by the tumor. PMID- 1312968 TI - Hepatic vascular and bile duct injury after ethanol injection therapy for hepatocellular carcinoma. AB - Three patients with serious hepatic vascular injury after percutaneous ethanol injection therapy for hepatocellular carcinoma (HCC) are described. In two cases, immediately after ethanol injection, liver function tests deteriorated and computed tomography (CT) showed a wedge-shaped low-density area due to liver infarction. In the other case, 1 year after ethanol injection, the intrahepatic bile duct in the right lobe was dilated and the right hepatic lobe atrophied. Endoscopic retrograde cholangiography showed stenosis of the main right hepatic duct. Since complications include both acute and delayed vascular injury after ethanol injection, patients should be followed for a long period after treatment. PMID- 1312969 TI - Ruptured hepatoma: detection with lipiodol angiography. AB - Hemorrhage from ruptured hepatoma is a serious complication. Transcatheter arterial embolization (TAE) is a choice of the treatment for control of hemorrhage. But conventional angiography may be useless for detection of bleeding site from ruptured hepatoma. We report two cases of ruptured hepatoma with detection of bleeding site by Lipiodol angiography. PMID- 1312970 TI - Characterization of insulinlike growth factor I receptors in human colon cancer. AB - A possible role of insulinlike growth factor I (IGF-I) and IGF-I receptors in the proliferation of human colon cancer has, to the best of the authors' knowledge, not been examined as yet. To determine a role of IGF-I in colon cancer, several human colon cancer cell lines and colon cancers were screened for specific binding to 125I-IGF-I. Almost all the human colon cancer cells examined were variably positive for specifically binding 125I-IGF-I. Almost half the colon cancer cell lines examined showed significant growth response to 6.6 nmol/L IGF I. Dose-dependent growth effects of exogenously added IGF-I (0.05-3.3 nmol/L) were shown in a representative human colon cancer cell line (Colo-205). To determine if IGF-I binding sites on colon cancer cells were similar or different from that described on other cells, the binding affinity, binding specificity, and molecular size of the IGF-I binding sites were characterized in representative human colon cancer cell lines (HCT-116 and Colo-205). The optimal binding assay conditions for measuring maximum number of 125I-IGF-I binding sites on the cells, in vitro, were determined and found to be similar to that described on other cells. Scatchard analysis of the specific binding data showed the presence of a single class of high-affinity binding sites [disassociation constant (Kd) = approximately 1.0-2.0 nmol/L], with a binding capacity of 1.0-2.0 x 10(5) sites per cell. The molecular weight of IGF-I receptors on cell membranes was determined by gel electrophoresis of the affinity cross-linked proteins, followed by autoradiography. A single band of binding proteins with a molecular mass of approximately 300 kilodaltons was evident under nonreducing conditions and separated out into two bands of approximately 240 and approximately 130 kilodaltons under reducing conditions. The 130-kilodalton band represents the alpha subunit of IGF-I receptors, and the 240-kilodalton band may represent aggregates of the receptor subunits that were not reduced completely. The widespread existence of high-affinity binding sites for IGF-I in established human colon cancer cell lines and freshly resected human colon cancers and the proliferative effect of IGF-I in several colon cancer cell lines, in vitro, reflect that IGF-I may be an important endocrine/paracrine/autocrine factor in the growth regulation of colon cancers in situ. PMID- 1312971 TI - Calcitonin gene-related peptide mediates the gastric hyperemic response to acid back-diffusion. AB - Disruption of the gastric mucosal barrier with resultant increased acid back diffusion leads to a marked increase in gastric mucosal blood flow (GMBF). This increase in GMBF is blocked by ablation of capsaicin-sensitive sensory neurons. The gastric arterioles are densely innervated by afferent neurons containing vasodilator peptides, calcitonin gene-related peptide (CGRP) being the most potent of these. We investigated (a) whether CGRP is the vasodilator mediator released by acid stimulation of capsaicin-sensitive sensory neurons and (b) whether the resultant hyperemia protects against the acid-induced mucosal injury. When the stomach was perfused with 0.15N HCl plus 15% ethanol, GMBF significantly increased by 70%. This hyperemic response was completely blocked by intra arterial infusion of human CGRP8-37 (500 pmol/min), a CGRP-receptor antagonist, close to the stomach. With the blockade of the hyperemic response to acid back diffusion, gross and histological mucosal damage were significantly aggravated. It is concluded that CGRP mediates the gastric hyperemic response to acid back diffusion and that this gastric hyperemic response is an important protective factor against acid-induced injury. PMID- 1312972 TI - Atriopeptins and Escherichia coli enterotoxin STa have different sites of action in mammalian intestine. AB - Studies with Escherichia coli-induced heat-stable enterotoxin (STa), an activator of intestinal particulate guanylate cyclase, have established an independent role for cyclic guanosine monophosphate (cGMP) as an intracellular mediator of intestinal salt and water secretion. The present study addressed whether atriopeptins (APs), known activators of particulate guanylate cyclase in other tissues, function as physiological agonists for cGMP-linked Cl- secretion in intestine. APs, in contrast to STa, caused no or only minor changes in cGMP levels in freshly isolated rat intestinal villus and crypt cells and in cultured human colon carcinoma cell lines (HT29glc-, CaCo-2, and T84). Conversely, APs, but not STa, induced a large increase in intracellular cGMP levels in the undifferentiated small intestinal cell lines IEC-6, IEC-18, and INT407. Addition of AP II (atrial natriuretic peptide fragment 5-27) to stripped mucosa of rat proximal colon in Ussing chambers caused a transient increase in the transepithelial potential difference (PD), which most likely represents an increase in Cl- secretion. In contrast, a sustained increase in PD was observed in response to STa or 8Br-cGMP. The AP II-provoked increase in PD was blocked by the neurotoxin tetrodotoxin. Immunohistochemical detection of cGMP in this tissue provided evidence for a different localization pattern of cells responding with an increase in cGMP levels to STa (colonocytes and goblet cells) or AP (specific cells in the submucosa) in rat proximal colon. This indicates that APs, unlike STa, do not directly stimulate the colonic epithelial cells but possibly provoke Cl- secretion by release of a neurotransmitter in the submucosa. PMID- 1312973 TI - Effect of colonic inflammation on mucin inhibition of Escherichia coli RDEC-1 binding in vitro. AB - Intestinal mucus protects the underlying epithelium against adhesion and invasion by microbial pathogens and their products. In inflamed colonic mucosa there are both histochemical and biochemical changes in the major organic constituent of mucus, goblet cell-derived mucin. To determine if these changes result in differences in functional properties of mucin, inhibition of adherence of piliated Escherichia coli, strain RDEC-1 (serotype O15:H-), by mucin purified from distal colons of normal rabbits was compared with inhibition by mucin from colons of rabbits with dinitrochlorobenzene-induced colitis. Histology from inflamed colons revealed evidence of chronicity with a chronic inflammatory cell infiltrate, depletion of mucous glands, and branching of crypts. Mucin was purified from crude mucus of distal colonic mucosa by sequential ultracentrifugation and characterized by gel electrophoresis and amino acid analysis. The rabbit enteropathogen RDEC-1 was grown to promote expression of adherence pili. A nonpiliated mutant, strain M34, was used as a negative control. A concentration-dependent inhibition of piliated RDEC-1 binding was shown using mucins derived from both inflamed and noninflamed colons. However, equivalent dry weights of mucin purified from inflamed colons showed less inhibition of bacterial binding (10.3% inhibition +/- 5.2%; mean +/- SD) compared with mucin from normal colons (47.6% +/- 10.8%; P less than 0.05). Mucin purified from additional animals with hapten-induced colitis but treated with the oral leukotriene B4-receptor antagonist SC-41930 showed intermediate inhibition of RDEC-1 binding (35.6% +/- 14.3%). It is concluded that mucin derived from inflamed distal colon of rabbits failed to inhibit in vitro binding of piliated RDEC-1, and by decreasing mucosal inflammation, this functional alteration of mucin was partially reversed. PMID- 1312974 TI - Verapamil alters eicosanoid synthesis and accelerates healing during experimental colitis in rats. AB - In inflammatory bowel disease, prostaglandins are mucosal protective whereas leukotrienes are proinflammatory. Recent evidence suggests that the formation and action of leukotrienes are calcium-dependent, whereas the formation and action of prostaglandins are not. To examine the possibility that, because of differential regulation of arachidonic acid metabolism, calcium channel blockade might alter mucosal eicosanoid synthesis and accelerate healing during inflammatory bowel disease, we treated a 4% acetic acid-induced colitis model with verapamil and/or misoprostol and determined the effects on colonic macroscopic injury, mucosal inflammation as measured by myeloperoxidase activity, in vivo intestinal fluid absorption, and mucosal prostaglandin E2 and leukotriene B4 (LTB4) levels as measured by in vivo rectal dialysis. In colitic animals, verapamil treatment significantly improved colonic fluid absorption and macroscopic ulceration. This mucosal-protective effect of verapamil occurred in the presence of a twofold reduction in mucosal LTB4 synthesis. In noncolitic animals, verapamil alone had no effect on in vivo fluid absorption, macroscopic ulceration, or myeloperoxidase activity but did induce a threefold reduction in LTB4 synthesis in addition to shifting arachidonic acid metabolism towards a sixfold stimulation of prostaglandin E2 synthesis. Our results show that, when administered before the experimental induction of colitis, the calcium channel blocker, verapamil, has a mucosal-protective effect that occurs as a consequence of reduced mucosal leukotriene synthesis and increased prostaglandin synthesis. This differential regulation of arachidonic acid metabolism may play an important role in the development of novel therapeutic agents for inflammatory bowel disease. PMID- 1312975 TI - Fecal and stomal bile acid composition after ileostomy or ileoanal anastomosis in patients with chronic ulcerative colitis and adenomatosis coli. AB - Fecal bile acids (FBA) were analyzed by gas-liquid chromatography in 29 patients [17 with ulcerative colitis (UC) and 12 with adenomatosis coli (AC)] and 5 healthy volunteers. Seven UC and 9 AC patients had undergone total colectomy and J-shaped ileal pouch-anal anastomosis (JAA). The mean daily FBA output was similar for JAA and terminal ileostomy patients (approximately 370 mg/day), and was about 1.5 times that of healthy Japanese volunteers (approximately 235 mg/day). The output of unconjugated bile acids, secondary bile acids, and 7 dehydroxylated bile acid was higher in JAA patients with UC than in terminal ileostomy patients, but there were no significant differences between the groups. The total fecal bacterial count in JAA patients was 10 times that in terminal ileostomy patients but was 1/10 of that in healthy volunteers. In patients with defunctioning high ileostomy, FBA output increased markedly (maximum, 3054 mg/day), and serum cholesterol levels were also significantly lower (P less than 0.05). These results suggest that after JAA the bile acid metabolism and fecal bacterial flora undergo more normalization than after terminal ileostomy. PMID- 1312976 TI - Absence of hepatitis C viral RNA from saliva and semen of patients with chronic hepatitis C. AB - Body fluids from 14 patients with chronic hepatitis C were analyzed for the presence of hepatitis C viral RNA using the polymerase chain reaction. Nucleic acids were extracted from serum, saliva, and semen in guanidinium thiocyanate, subjected to reverse transcription, and then amplified by a double polymerase chain reaction technique using "nested" primers from the highly conserved 5' non coding region of the hepatitis C virus genome. Hepatitis C viral RNA was found in the serum of all patients in titers ranging between 10(-1) and 10(-3). The hepatitis C viral genome was not detected in any saliva or semen sample. These findings suggest that body fluids of patients with chronic hepatitis C are rarely, if ever, contaminated with the hepatitis C virus. This may help to explain the infrequent transmission of this disease by sexual or close physical contact. PMID- 1312977 TI - Atrial natriuretic factor in experimental cirrhosis in rats. AB - Atrial natriuretic factor (ANF) is a cardiac hormone with potent natriuretic, diuretic, and vasorelaxant properties. Although abnormalities in ANF release, plasma level, and renal receptors have been described in humans and/or animals with cirrhosis and ascites, little is known about the ANF hormonal system in cirrhosis without ascites. The aim of this study was to examine the ANF hormonal system in an animal model of cirrhosis to determine whether compensated cirrhosis is associated with changes in the ANF hormonal system. Pair-fed rats were studied 5-7 weeks after either sham surgery or bile duct ligation. Bile duct-ligated (BDL) rats had elevated portal pressure and cirrhosis but did not have ascites. ANF messenger RNA levels were increased onefold in the atria of BDL rats. Sham operated and BDL rats had similar plasma ANF levels. Competitive binding inhibition studies of isolated glomeruli showed a single class of receptors in sham-operated and BDL rats. The equilibrium dissociation constant was similar in sham-operated (0.51 nmol/L) and BDL (0.63 nmol/L) rats. Glomerular ANF receptor density increased significantly in BDL rats. Cyclic guanosine monophosphate generation in isolated glomeruli in response to 100 nmol/L ANF decreased slightly but not significantly in BDL rats. It was concluded that the ANF hormonal system is altered in cirrhosis without ascites; atrial messenger RNA level and glomerular ANF receptor density are increased. PMID- 1312978 TI - Community-acquired hepatitis C virus infection. PMID- 1312979 TI - Sequence analysis of active mariner elements in natural populations of Drosophila simulans. AB - Active and inactive mariner elements from natural and laboratory populations of Drosophila simulans were isolated and sequenced in order to assess their nucleotide variability and to compare them with previously isolated mariner elements from the sibling species Drosophila mauritiana and Drosophila sechellia. The active elements of D. simulans are very similar among themselves (average 99.7% nucleotide identity), suggesting that the level of mariner expression in different natural populations is largely determined by position effects, dosage effects and perhaps other factors. Furthermore, the D. simulans elements exhibit nucleotide identities of 98% or greater when compared with mariner elements from the sibling species. Parsimony analysis of mariner elements places active elements from the three species into separate groups and suggests that D. simulans is the species from which mariner elements in D. mauritiana and D. sechellia are most likely derived. This result strongly suggests that the ancestral form of mariner among these species was an active element. The two inactive mariner elements sequenced from D. simulans are very similar to the inactive peach element from D. mauritiana. The similarity may result from introgression between D. simulans and D. mauritiana or from selective constraints imposed by regulatory effects of inactive elements. PMID- 1312980 TI - Dosage compensation of the copia retrotransposon in Drosophila melanogaster. AB - Dosage compensation in Drosophila has been studied at the steady state RNA level for several single-copy genes; however, an important point is addressed by analyzing a repetitive, transposable element for dosage compensation. The two issues of gene-specific cis control and genomic position can be studied by determining the extent of dosage compensation of a transposable element at different chromosomal locations. To determine whether the multicopy copia transposable element can dosage compensate, we used the X-linked white-apricot (wa) mutation in which a copia element is present. The extent of dosage compensation was determined for the white and copia promoters in larvae and adults in two different genomic locations of the wa allele. We conclude that copia is able to dosage compensate, and that the white promoter and the copia promoter are not coordinate in their dosage compensation abilities when assayed under these various conditions. Thus, two transcriptional units, one within the other, both of which are able to dosage compensate, do so differently in response to developmental stage and genomic position. PMID- 1312981 TI - Molecular analysis of Ac transposition and DNA replication. AB - Molecular events associated with transposition of the mobile element Activator (Ac) from the P locus of maize have been examined in daughter lineages of twinned sectors. Genetic and molecular analyses indicate that the donor Ac has excised from only one of the two daughter chromosomes in these lineages. Cloning and sequence analyses of target sites on daughter chromosomes indicate that Ac insertion can occur either before or after the completion of DNA replication. Transpositions from a replicated donor site to both unreplicated and replicated target sites imply that most transpositions of Ac occur during or shortly after the S phase of the cell cycle. PMID- 1312982 TI - The yeast SFL2 gene may be necessary for mating-type control. AB - We previously reported the isolation of the yeast suppressor gene for flocculation, SFL2 (TUP1). SFL2 gene disruption results in pleiotropic phenotypes; the sfl2 null mutation also causes a morphological change similar to shmoo in both the MAT alpha and MATa/alpha cells. The MAT alpha and MATa/alpha sfl2 null mutant cells incorporate chitin into the new growth zone in the same way as the alpha-factor-treated MATa cells. In order to clarify the molecular basis of this morphological change, we examined the effect of the sfl2 null mutation on the mRNA production of various genes involved in mating-type control. The transcripts of both the STE2 (an a-specific gene) and STE3 (an alpha specific gene) genes are detected in the MAT alpha and MATa/alpha cells carrying the sfl2 null mutation. In addition, mRNA of the GPA1 gene (haploid-cell-specific gene) is also detected in the MATa/alpha sfl2 cells. However, there is no significant difference in the levels of the MAT alpha 2 and MATa1 transcripts. These results suggest that the SFL2 gene product may be necessary for alpha 2 and a1-alpha 2 repression. PMID- 1312983 TI - Purification and N-terminal amino acid sequences of two polypeptides encoded by the mcrB gene from Escherichia coli K-12. AB - This report provides a purification method for the two proteins, 51 kDa and 33 kDa, both encoded by the same mcrB gene of the McrBC restriction system in Escherichia coli K-12. The two proteins were produced in large quantity using a T7 expression system and copurified to near homogeneity by DEAE-Sepharose and Affi-Gel blue column chromatography. The N-terminal amino acid sequences of these purified McrB proteins were the same as those predicted from the mcrB DNA sequence by Ross et al. [J. Bacteriol. 171 (1989b) 1974-1981]. The 33-kDa protein totally overlaps the C-terminal part of the 51-kDa protein. PMID- 1312984 TI - Hydroxypyridinium collagen cross-links in human liver fibrosis: study of alveolar echinococcosis. AB - Liver samples from patients with three different types of liver diseases, alveolar echinococcosis (a dense and irreversible fibrosis), hepatocellular carcinoma and alcoholic cirrhosis, were analyzed for their content in hydroxypyridinium cross-links found in mature collagen. We demonstrated the presence of small amounts of pyridinoline in control livers (0.27 +/- 0.06 pmol/pmol of collagen). Pyridinoline content was increased in fibrotic livers, with the highest values found in patients with alveolar echinococcosis (up to 1.33 pmol/pmol of collagen). The deoxy analogue of pyridinoline was not detected in either normal or fibrotic livers. Pyridinoline levels, expressed as picomoles per picomole of collagen, were similar in all patients with carcinoma (0.7 +/- 0.05 pmol/pmol of collagen). They were heterogeneous in patients with alveolar echinococcosis and were particularly high in patients with alcoholic cirrhosis (1.04 +/- 0.11 pmol/pmol of collagen). These results demonstrate for the first time the presence of an hydroxypyridinium cross-link in liver fibrosis and suggest that pyridinoline measurement might be an important criterion in assessing the irreversibility of human liver fibrosis. PMID- 1312985 TI - Survival and prognostic factors in 212 Italian patients with genetic hemochromatosis. AB - Two hundred twelve Italian patients with genetic hemochromatosis (181 men, mean age 50 +/- 11 yr; and 31 women, mean age 49 +/- 10 yr) were followed for a median period of 44 mo (range = 3 to 218 mo). Alcohol abuse was present in 31 subjects (15%), and chronic HBV and HCV infection were seen in 19 (9%) and 35 (24%) of 145 cases tested, respectively. Twenty-four patients (11%) had concomitant beta thalassemia trait. Liver biopsy revealed cirrhosis in 146 and a noncirrhotic pattern in the other 66. Perls' stain was degree III in 37 patients and IV in 171 patients. One hundred eighty-five patients underwent weekly venesection, and iron depletion was achieved in 122 cases after total iron removal of 3 to 41 gm. Death occurred in 44 patients after 3 to 198 mo and was due to hepatocellular carcinoma in 20 cases, liver failure in 10, extrahepatic cancer in six, heart failure in three and hemochromatosis unrelated causes in five. Cancer has developed in seven other patients still alive (hepatocellular in five and extrahepatic in two). No deaths were observed among noncirrhotic patients; cumulative survival rates in cirrhotic patients were 85%, 75%, 60% and 47% at 3, 5, 8 and 10 yr, respectively. Univariate analysis in the 146 cirrhotic patients showed that age greater than 60 yr, alcohol abuse, cardiomyopathy, skin pigmentation, portal hypertension, hypoalbuminemia, hypergammaglobulinemia and Child class B or C had significant negative prognostic value. At multivariate analysis, only alcohol abuse, gamma globulins greater than 2.0 gm/dl and Child class B or C maintained their negative prognostic values (p less than 0.01, hazard ratio 2.7; p less than 0.001, hazard ratio 2.8; and p less than 0.001, hazard ratio 4.3, respectively). PMID- 1312986 TI - A chromosome 17:7 translocation is associated with a hepatitis B virus DNA integration in human hepatocellular carcinoma DNA. AB - Chronic hepatitis B virus infection is often associated with major structural rearrangements of both the integrated viral DNA and the associated cellular sequences. We present here the structure of a single-copy hepatitis B virus insert cloned from human hepatocellular carcinoma DNA recently reported to encode a novel transcriptional trans-activator function. The hepatitis B virus portion of the clone consists of two colinear fragments covering the X gene with its promoter and enhancer (nucleotides 717 to 1796) and a 3' truncated pre-S/S gene (nucleotides 2703 to 423). The lack of the entire pre-C/C gene caused a fusion of the 3' end of the X gene with sequences upstream from the pre-S gene. The structure of the integrated viral DNA fragments suggests insertion of hepatitis B virus replication intermediates into cellular DNA and subsequent recombination between these primary integrations to generate the final structure of the clone. The 5' and 3' cellular flanking sequences mapped to the centromeric alpha satellite DNA of chromosome 17 and to the short arm of chromosome 7 (p14-pter), respectively, indicating that chromosomal translocation was associated with the hepatitis B virus DNA integration. Because this is the fourth case reported in which hepatitis B virus-associated rearrangements have affected chromosome 17, it is conceivable that a loss of important cellular genes (such as the p53 antioncogene on chromosome 17) may be a crucial step in hepatitis B virus-related hepatocarcinogenesis. PMID- 1312987 TI - Three different patterns of hepatitis C virus infection in chimpanzees. AB - The relationship between hepatitis C virus RNA and hepatitis C virus-associated antibodies (antibody against the putative capsid protein and C-100 antibody) was determined by nested polymerase chain reaction and enzyme-linked immunosorbent assay in serial serum samples obtained from eight chimpanzees experimentally infected with hepatitis C virus. Three different patterns emerged from the polymerase chain reaction data: the first (group 1) was acute resolving hepatitis with transient appearance of HCV RNA (two cases). The second (group 2) had chronic hepatitis with persistent hepatitis C virus RNA positivity (four cases) and the third (group 3) had chronic hepatitis with intermittent appearance of hepatitis C virus RNA (two cases). In four of eight animals, hepatitis C virus RNA was first detectable in serum 1 wk after inoculation. Although serum HCV RNA was detected in all infected chimpanzees, two were positive only for antibody against the putative capsid protein, whereas two were positive only for antibody to C-100 antigen. In four of eight cases, antibody against the putative capsid protein appeared earlier than did antibody to C-100 antigen, was detected just before or coincident with rising glutamate pyruvate transaminase values and remained positive for a long time even after recovery. Six of eight animals (75%) were still hepatitis C virus RNA positive 1 yr after inoculation, suggesting that the risk of development of the chronic carrier state is high in hepatitis C virus infection. Furthermore, there did not appear to be a good correlation between antibody titer in serum and hepatitis C virus infectivity titer. PMID- 1312988 TI - Atrial natriuretic peptide in portal vein-ligated rats: alterations in cardiac production, plasma level and glomerular receptor density and affinity. AB - The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/ 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1312989 TI - Genetic structure and heterogeneity of hepatitis C virus: a vaccine impediment? PMID- 1312991 TI - PCR-assisted localization of the human SRPR gene. AB - A polymerase chain reaction (PCR)-based assay has been designed that detects the presence of the human signal recognition particle receptor (SRPR) gene in inter species somatic cell hybrids. By using hybrids containing various fragments of chromosome 11q, SRPR has been mapped to a chromosomal region flanked by the 11q23 and 11q24 breakpoints associated with the constitutional and neuroepithelioma (11;22) translocations, respectively. PMID- 1312990 TI - Complementation of a DNA repair deficiency in six human tumor cell lines by chromosome 11. AB - Human tumor cells, after x-irradiation during the G2 phase of the cell cycle, show an abnormally high frequency of persistent chromatid breaks and gaps resulting from deficient DNA repair. Addition of a single human chromosome 11 from normal fibroblasts by micro-cell fusion to cell lines from six different tumors resulted in efficient repair of the radiation-induced damage to the level in normal cells. For one of the cell lines, addition of the long arm of chromosome 11 was sufficient to restore repair efficiency. In four of the six tumor lines, restoration of efficient DNA repair by chromosome 11 was associated with tumor suppression in nude mice. These results suggest that chromosome 11 carries a DNA repair gene or genes that complement the repair deficiency of tumor cells and that this gene for at least one tumor is localized to the long arm. PMID- 1312992 TI - PKU mutations R408Q and F299C in Norway: haplotype associations, geographic distributions and phenotype characteristics. AB - Details are given concerning the phenylketonuria (PKU) mutations R408Q and F299C. Both mutations were identified among 47 PKU patients, derived from the Norwegian PKU registry. A novel PKU mutation (R408Q) was identified, by single-strand conformation polymorphism analysis, on six out of eight mutant haplotype 12 chromosomes and on none of the other PKU chromosomes. The F299C mutation occurred exclusively on mutant haplotype 8, and was the only mutation associated with this haplotype (on six chromosomes). One patient homozygous for each mutation was found. The patient homozygous for F299C manifested severe PKU, whereas the R408Q homozygote exhibited a mild PKU variant. Pedigree analysis of these families has not, so far, revealed consanguinity. Information on the place of birth of the relevant grandparents of the PKU patients with these mutations suggests that each of these mutations in Norway has originated from a common gene source. PMID- 1312993 TI - Detection by DGGE of a new polymorphism closely linked to the adenomatous polyposis coli region. AB - The EF5.44 locus is in close proximity to the chromosome 5 region to which the genetic defect responsible for familial adenomatous polyposis has been mapped. We have devised two oligonucleotides that promote the specific polymerase chain reaction (PCR) amplification of a 365-bp sequence in this region. Analysis by denaturing gradient gel electrophoresis of the resulting fragment has unravelled individual differences that could be identified as a single base pair change in a MnlI restriction site. This PCR assayable polymorphism increases the informativeness at this locus, and should be useful in the presymptomatic diagnosis of familial adenomatous polyposis. PMID- 1312994 TI - Protein kinase C activation modulates tumour necrosis factor-alpha priming of human neutrophils for zymosan-induced leukotriene B4 release. AB - Neutrophil (PMN) activation by the yeast component zymosan involves the complement receptor type 3 (CD11b/CD18). Recombinant human tumour necrosis factor alpha (rhTNF-alpha) augmented the zymosan-stimulated leukotriene B4 (LTB4) release from PMN, reaching a fourfold increase at 10(-9) M. Co-incubation of PMN with 10(-9) M rhTNF-alpha and staurosporine resulted in a further dose-dependent increase, which became significantly greater than a purely additive effect at a staurosporine concentration of 10 nM. This synergy was maintained at all doses of staurosporine tested. In addition, doses of phorbol 12-myristate 13-acetate (PMA) that do not activate protein kinase C (PKC) (below 10(-9) M) also augmented the zymosan-stimulated release of LTB4. However, doses of PMA above 10(-9) M progressively inhibited the response to levels below that of zymosan alone. Staurosporine at 50 nM completely prevented, and 10(-9) M rhTNF-alpha partially but significantly (P less than 0.02 at 10(-8) M PMA, P less than 0.01 at 10(-7) M PMA) reversed, this high-dose PMA inhibition. PKC activation thus opposes the priming effect of rhTNF-alpha on neutrophils, while PKC inhibition may enhance the ability of rhTNF-alpha to prime PMN for zymosan activation. The combined effect of rhTNF-alpha and staurosporine suggests an intracellular synergy rather than simply a direct action due to increased zymosan receptor expression. Thus there appear to be mechanisms whereby the responses of neutrophils may be augmented without activating PKC. Indeed, kinase activation may even exert a degree of feedback control that is antagonized by rhTNF-alpha treatment. PMID- 1312995 TI - Cytokine-induced (interleukins-3, -6 and -8 and tumour necrosis factor-beta) activation and deactivation of human neutrophils. AB - The effect of various cytokines [interleukin-3(IL-3), IL-6, IL-8, tumour necrosis factor-beta (TNF-beta)] on human neutrophils (PMN) was analysed with regard to the generation of leukotrienes and the involvement of guanosine triphosphate (GTP)-binding proteins (G proteins). Incubation of cytochalasin B-pretreated PMN with cytokines alone did not lead to a generation of leukotrienes. However, the cytokines affected the formyl-methionyl-leucyl-phenylalanine-(FMLP)-induced formation of leukotrienes in a time-dependent manner. Preincubation of the cells with the different cytokines for short periods (15 seconds at 37 degrees) enhanced the subsequent FMLP-induced leukotriene generation, whereas preincubation for prolonged times resulted in a reduced formation of leukotrienes. These results correlated with the respective G protein-associated guanosine triphosphatase (GTPase) activities within isolated membrane fractions. The present study indicates a modulation of the FMLP-induced leukotriene formation by diverse cytokines via interaction with the GTP-binding proteins. PMID- 1312996 TI - Pedunculated hepatoma. PMID- 1312998 TI - Rhizobium leguminosarum CFN42 lipopolysaccharide antigenic changes induced by environmental conditions. AB - Four monoclonal antibodies were raised against the lipopolysaccharide of Rhizobium leguminosarum bv. phaseoli CFN42 grown in tryptone and yeast extract. Two of these antibodies reacted relatively weakly with the lipopolysaccharide of bacteroids of this strain isolated from bean nodules. Growth ex planta of strain CFN42 at low pH, high temperature, low phosphate, or low oxygen concentration also eliminated binding of one or both of these antibodies. Lipopolysaccharide mobility on gel electrophoresis and reaction with other monoclonal antibodies and polyclonal antiserum indicated that the antigenic changes detected by these two antibodies did not represent major changes in lipopolysaccharide structure. The antigenic changes at low pH were dependent on growth of the bacteria but were independent of nitrogen and carbon sources and the rich or minimal quality of the medium. The Sym plasmid of this strain was not required for the changes induced ex planta. Analysis of bacterial mutants inferred to have truncated O polysaccharides indicated that part, but not all, of the lipopolysaccharide O polysaccharide portion was required for binding of these two antibodies. In addition, this analysis suggested that O-polysaccharide structures more distal to lipid A than the epitopes themselves were required for the modifications at low pH that prevented antibody binding. Two mutants were antigenically abnormal, even though they had abundant lipopolysaccharides of apparently normal size. One of these two mutants was constitutively unreactive toward three of the antibodies but indistinguishable from the wild type in symbiotic behavior. The other, whose bacteroids retained an epitope normally greatly diminished in bacteroids, was somewhat impaired in nodulation frequency and nodule development. PMID- 1312997 TI - Genetic analysis of the Tn21 mer operator-promoter. AB - The mercury resistance operon, mer, of the transposon Tn21 is transcribed from two overlapping divergent promoters: PR for the regulatory gene, merR, and PTPCAD for the structural genes, merTPCAD. Transcription of merTPCAD is repressed in the absence of Hg(II) and activated in the presence of Hg(II) by the regulatory protein, MerR. In addition, MerR represses its own expression regardless of the presence of Hg(II). MerR binds as a dimer to a single region of dyad symmetry lying between the -35 and -10 hexamers of PTPCAD. Analysis of the expression of transcriptional fusions to hydroxylamine- and oligonucleotide-generated mutants of this divergent operator-promoter region identified key bases involved in MerR dependent repression of PTPCAD and of PR and in activation of PTPCAD. Six of the seven mutants affecting the palindromic region were altered in their ability to bind the MerR protein in vitro as measured by fragment retardation assays. These differences in in vitro MerR binding correlated well with the in vivo measurements of repression or of activation. Bases identified as functionally relevant by this genetic analysis coincide extensively with those previously identified as relevant via in vivo footprinting. Four major points emerge from this analysis: (i) transition and transversion mutations within the spacer between the -10 and -35 hexamers of PTPCAD generally have little effect on the MerR-independent (i.e., unregulated) expression of either promoter; (ii) alteration of certain bases in the MerR-binding dyad affects repression of PTPCAD differently than repression of PR; (iii) certain dyad changes can impair activation of PTPCAD more severely than repression of this promoter; and (iv) mutations in the -10 hexamer of PTPCAD which also effect PR expression define one of two potential -10 hexamers in PR as actually functional in vivo. PMID- 1312999 TI - A single regulatory gene integrates control of vitamin B12 synthesis and propanediol degradation. AB - The cob operon of Salmonella typhimurium encodes enzymes required for synthesis of adenosyl-cobalamin (vitamin B12). The pdu operon encodes enzymes needed for use of propanediol as a carbon source, including an adenosyl-cobalamin-dependent enzyme, propanediol dehydratase. These two operons both map near min 41 of the S. typhimurium linkage map and are transcribed divergently. Here we report that the cob and pdu operons form a single regulon. Transcription of this regulon is induced by either glycerol or propanediol. The metabolism of these compounds is not required for induction. Propanediol induces the regulon either aerobically or anaerobically during growth on poor carbon sources. Aerobically glycerol induces only if its metabolism is prevented by a mutational block such as a glpK mutation. Under anaerobic conditions, glycerol induces in both glpK+ and glpK mutant strains during growth on poor carbon sources. A new class of mutations, pocR, prevents induction of the cob/pdu regulon by either propanediol or glycerol and causes a Cob- Pdu- phenotype. The pocR gene is located between the cob and pdu operons and appears to encode a trans-acting protein that acts as a positive regulator of both operons. Transcription of the pocR regulatory gene is induced, even without the PocR protein, during aerobic growth on poor carbon sources and during anaerobic respiration. With the functional PocR protein, transcription of the pocR gene is autoinduced by propanediol but not by glycerol. The growth conditions that increase pocR gene expression correlate with growth conditions that allow high induction of the cob/pdu regulon. A model for control of this regulon suggests that the PocR protein is a transcriptional activator of both the cob and pdu operons and that both glycerol and propanediol can individually serve as effectors of the PocR protein. We suggest that global control mechanisms cause variation in the level of the PocR protein; an increased level of the PocR protein permits higher induction by propanediol or glycerol. PMID- 1313000 TI - The poc locus is required for 1,2-propanediol-dependent transcription of the cobalamin biosynthetic (cob) and propanediol utilization (pdu) genes of Salmonella typhimurium. AB - In this communication we present evidence that indicates that 1,2-propanediol (1,2-PDL) is a positive effector of the transcription of the cobalamin (vitamin B12) biosynthetic (cob) operon and of the 1,2-PDL utilization (pdu) genes. The stimulatory effects of 1,2-PDL were demonstrated using Mu d-lac transcriptional fusions to cob and pdu. Significantly increased levels of transcription of the cob and pdu operon fusions were measured in cultures grown under both anoxic and highly aerated conditions when 1,2-PDL was present in the culture medium. We have isolated mutants that carry lesions that render both pdu and cob transcription unresponsive to 1,2-PDL. These mutations were mapped to the region between cob and pdu (41 min), and they define the poc locus PDL and cobalamin). The poc locus is required for the positive regulatory effects of 1,2-PDL to be exerted. Complementation of Poc function was achieved in trans by an F' plasmid carrying the poc+ locus, suggesting that at least one diffusible product regulates the expression of cob and pdu in S. typhimurium. PMID- 1313001 TI - Interaction between DNA and alpha/beta-type small, acid-soluble spore proteins: a new class of DNA-binding protein. AB - DNA in spores of Bacillus and Clostridium species is associated with small, acid soluble proteins (SASP) of the alpha/beta type; the presence of these proteins is a major factor in causing spore resistance to UV light, alpha/beta-type SASP did not bind to single-stranded DNA, single- or double-stranded RNA, or DNA-RNA hybrids in vitro. However, these proteins bound a variety of double-stranded DNAs and conferred protection against DNase cleavage. The binding of alpha/beta-type SASP to DNA saturated at a protein/DNA ratio (wt/wt) of 4:1 to 5:1, which is approximately 1 SASP per 4 bp. alpha/beta-type SASP-DNA interaction did not require divalent cations, was independent of pH between 6 and 8, and, for some SASP-DNA pairs, was relatively insensitive to salt up to 0.3 M. The relative affinity of alpha/beta-type SASP for different DNAs was poly(dG).poly(dC) greater than poly(dG-dC).poly(dG-dC) greater than plasmid pUC19 greater than poly(dA dT).poly(dA-dT), with poly(dA).poly(dT) giving no detectable binding. This order in alpha/beta-type SASP-DNA affinities parallels the facility with which the DNAs adopt an A-like conformation, the conformation in alpha/beta-type SASP-DNA complexes. An oligo(dG).oligo(dC) of 12 bp was bound by alpha/beta-type SASP. While a 26-bp oligo(dG).oligo(dC) bound more tightly than the 12-mer, there was no significant increase in affinity for alpha/beta-type SASP with further increase in size of oligo(dG).oligo(dC). In contrast, binding of alpha/beta-type SASP to oligo(dA-dT).oligo(dA-dT) was minimal up to at least a 70-mer, and binding to poly(dA-dT).poly(dA-dT) was very cooperative. In addition to blocking DNase digestion, binding of alpha/beta-type SASP to DNA blocked (i) cleavage of the DNA backbone by hydroxyl radicals and orthophenanthroline-Cu2+, (ii) DNA cleavage by restriction enzymes, in particular those with specificity for GC-rich sequences; and (iii) in vitro transcription of some but not all genes. However, methylation of dG residues by dimethyl sulfate was not affected by alpha/beta type SASP binding. PMID- 1313002 TI - Genome maps of Campylobacter jejuni and Campylobacter coli. AB - Little information concerning the genome of either Campylobacter jejuni or Campylobacter coli is available. Therefore, we constructed genomic maps of C. jejuni UA580 and C. coli UA417 by using pulsed-field gel electrophoresis. The genome sizes of C. jejuni and C. coli strains are approximately 1.7 Mb, as determined by SalI and SmaI digestion (N. Chang and D. E. Taylor, J. Bacteriol. 172:5211-5217, 1990). The genomes of both species are represented by single circular DNA molecules, and maps were constructed by partial restriction digestion and hybridization of DNA fragments extracted from low-melting-point agarose gels. Homologous DNA probes, encoding the flaAB and 16S rRNA genes, as well as heterologous DNA probes from Escherichia coli, Bacillus subtilis, and Haemophilus influenzae, were used to identify the locations of particular genes. C. jejuni and C. coli contain three copies of the 16S and 23S rRNA genes. However, they are not located together within an operon but show a distinct split in at least two of their three copies. The positions of various housekeeping genes in both C. jejuni UA580 and C. coli UA417 have been determined, and there appears to be some conservation of gene arrangement between the two species. PMID- 1313004 TI - Identification of a missing link in glycosylphosphatidylinositol anchor biosynthesis in mammalian cells. AB - A large number of mammalian proteins are anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. Biosynthetic intermediates of the GPI anchor have been identified in mammalian cells. The early GPI precursors are sensitive to phosphatidylinositol (PI)-specific phospholipase C (PLC). However, all of the later GPI precursors, which contain 1 or more mannose residues, are PI PLC-resistant, suggesting that there is another unidentified precursor. Here, we report the identification of this missing link. This GPI precursor can only be labeled with glucosamine and inositol, and is resistant to PI-PLC but sensitive to GPI-phospholipase D. It accumulates in large quantity only in mutants which are defective in the addition of the first mannose residue to the elongating GPI core. Thus, fatty acylation of glucosaminylphosphatidylinositol, to render it PI PLC-resistant, is an obligatory step in the biosynthesis of mammalian GPI anchor precursors. PMID- 1313003 TI - Spectroscopic and genetic evidence for two heme-Cu-containing oxidases in Rhodobacter sphaeroides. AB - It has recently become evident that many bacterial respiratory oxidases are members of a superfamily that is related to the eukaryotic cytochrome c oxidase. These oxidases catalyze the reduction of oxygen to water at a heme-copper binuclear center. Fourier transform infrared (FTIR) spectroscopy has been used to examine the heme-copper-containing respiratory oxidases of Rhodobacter sphaeroides Ga. This technique monitors the stretching frequency of CO bound at the oxygen binding site and can be used to characterize the oxidases in situ with membrane preparations. Oxidases that have a heme-copper binuclear center are recognizable by FTIR spectroscopy because the bound CO moves from the heme iron to the nearby copper upon photolysis at low temperature, where it exhibits a diagnostic spectrum. The FTIR spectra indicate that the binuclear center of the R. sphaeroides aa3-type cytochrome c oxidase is remarkably similar to that of the bovine mitochondrial oxidase. Upon deletion of the ctaD gene, encoding subunit I of the aa3-type oxidase, substantial cytochrome c oxidase remains in the membranes of aerobically grown R. sphaeroides. This correlates with a second wild type R. sphaeroides is grown photosynthetically, the chromatophore membranes lack the aa3-type oxidase but have this second heme-copper oxidase. Subunit I of the heme-copper oxidase superfamily contains the binuclear center. Amino acid sequence alignments show that this subunit is structurally very highly conserved among both eukaryotic and prokaryotic species. The polymerase chain reaction was used to show that the chromosome of R. sphaeroides contains at least one other gene that is a homolog of ctaD, the gene encoding subunit I of the aa3-type cytochrome c oxidase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313005 TI - Characterization of the recombinant human receptor for Escherichia coli heat stable enterotoxin. AB - We report here the molecular characterization of a recombinant cell line (293 STaR) expressing the heat-stable enterotoxin receptor (STaR) from human intestine. We have compared the 293-STaR cell line with the human colonic cell line T84 that endogenously expresses STa binding sites. Scatchard analysis of displacement binding studies revealed a single STa binding site with an affinity (Ki) of 97 pM in 293-STaR compared with 55 pM in T84 cells. Saturation isotherms of STa binding gave a Kd of 94 pM for the cloned receptor expressed in 293 cells and 166 pM for the receptor present in T84 cells. Kinetic measurements of STa binding to 293-STaR gave an association rate constant, K1, of 2.4 x 10(8) M-1 min 1 and a dissociation rate constant, K2, of 0.016 min-1. The half-time of dissociation was 43 min, and the Kd calculated from the ratio of the kinetic constants was 67 pM. The pH profile of STa binding showed that the number of STa binding sites is increased 3-fold at pH 4.0 compared with pH 7.0, with no effect on binding affinity. A polyclonal antibody directed against the extracellular domain of STaR immunoprecipitated two proteins of approximately 140 and 160 kDa from both 293-STaR and T84 cells. Cross-linking of 125I-STa to 293-STaR cells resulted in the labeling of proteins with a molecular mass of approximately 153, 133, 81, 68, 56, and 49 kDa, the two smallest being the more abundant. Similar results have been reported for the STaR present on rat brush border membranes. These data suggest that the STaR-guanylyl cyclase identified by molecular cloning is the only receptor for STa present in T84 cells. PMID- 1313006 TI - Enhancement of phospholipase C delta 1 activity in the aortas of spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR), which develop hypertension approximately 10 weeks after birth, are considered to provide a good animal model for human essential hypertension. We report here that the abnormal activation of phospholipase C delta 1 (PLC-delta 1) may be one of the main causes of hypertension. Levels of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol are found to be higher in the aortas of 12-week-old SHR than in age-matched normotensive Wistar-Kyoto rats (WKY), although the levels in the aortas of 7-week-old SHR, which have normal blood pressure, are the same as in WKY. Moreover, PLC activity is also higher in the aortas of 12-week-old SHR. Judging from Western blot analysis and immunoabsorption of PLCs, this activation is found to be due to that of PLC-delta 1. PLC-delta 1 from rat aorta is expressed significantly from 7 to 12 weeks, which correlates with the development of hypertension in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is more markedly activated at low Ca2+ concentration than that of age-matched WKY. These results suggest that the abnormal enhancement of PLC-delta 1 activity is responsible for accumulation of inositol 1,4,5-trisphosphate and diacylglycerol, leading to continuous hypertonicity of vascular smooth muscle in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is significantly higher at low Ca2+ concentration than that of normotensive WKY. PMID- 1313007 TI - Effects of gelsolin on human platelet cytosolic phosphoinositide-phospholipase C isozymes. AB - The effective resolution of human platelet cytosolic phosphoinositide phospholipase C (PLC) revealed five distinct activity peaks by Q-Sepharose and heparin-Sepharose column chromatographies when assayed using phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2). The results of Western blotting analysis with various antibodies against PLC isozymes showed that peak Ia (PLC-delta type), peak-Ib (PLC-gamma 1 type), and peak-IIc (PLC-beta type) and two unidentified activity peaks (PLC-IIa and PLC-IIb) were present in human platelet cytosol. A protein with guanosine 5'-3-O-(thio)triphosphate-binding activity was coeluted with the PLC-IIa and was purified to homogeneity. It exhibited 86- and 42-kDa polypeptide bands upon sodium dodecyl sulfate polyacrylamide gel electrophoresis which were identified as gelsolin and actin by immunostaining, respectively. Large amounts of gelsolin/actin (1:1) complex "gelsolin complex" were detected in the PLC-delta and PLC-gamma 1 fractions. The PLC-gamma 1 and the gelsolin complex were co-immunoprecipitated by the antibody raised against PLC-gamma 1. Furthermore, the partially purified bovine brain PLC gamma 1 fraction also was found to be associated with the gelsolin complex and the association was released by the addition of 1% sodium cholate. This finding has prompted us to examine effects of the gelsolin complex and the free gelsolin on activities of the above PLC isoforms from platelet cytosol. The gelsolin complex did not affect the PIP2 hydrolyzing activities of all PLC isoforms. In contrast, the purified gelsolin inhibited distinctly PIP2 hydrolyses by PLC-Ia (delta), PLC-Ib (gamma 1), and PLC-IIa (unidentified), whereas the inhibitory effects for PLC-IIb (unidentified) and PLC-IIc (beta) were moderate. The inhibitory effect of gelsolin on PIP2-hydrolysis by PLC-gamma 1 was diminished by a large amount of PIP2 substrate. These results suggested that the inhibition of PLC by gelsolin is due to sequestration of substrate PIP2 by its competitive binding. PMID- 1313008 TI - A rabbit reticulocyte ubiquitin carrier protein that supports ubiquitin-dependent proteolysis (E214k) is homologous to the yeast DNA repair gene RAD6. AB - The two isoforms of the 14-kDa ubiquitin carrier protein (E2(14k)) are unique among rabbit E2s in efficiently supporting ubiquitin-protein ligase (E3)-mediated ubiquitination of proteins destined for degradation. To begin determining the structural basis for this property, we have isolated a cDNA encoding the predominant reticulocyte isoform of the E2 from a rabbit skeletal muscle library. The sequence predicts a protein of 152 amino acids with a molecular weight of 17,293. Expression of the cDNA in Escherichia coli and purification of the recombinant protein revealed an E2 with high affinity for E3 and ubiquitin activating enzyme (E1). The latter high affinity interaction appears to be between the ubiquitin charged form of E1 and the uncharged form of E2 and does not result in a stable complex between these two enzymes. The predicted sequence shows regions of strong homology with other sequenced E2s, suggesting that these regions may be involved in binding to E1 and/or in ubiquitin transfer from E1, functions common to all E2s. Surprisingly, the E2(14k)) sequence is markedly more similar to Saccharomyces cerevisiae RAD6 (69% identity) than to its proposed homologs UBC4/UBC5 (38% identity). The sequence is identical to that recently reported for a human 17-kDa E2 which can complement rad6 mutants thereby identifying rabbit E2(14k) as a RAD6 homologue. The biochemical properties of this previously uncharacterized human 17-kDa E2 are now defined and its misassignment as a homologue of rabbit E2(17k) is corrected. Our findings resolve current confusion regarding relationships among E2s and define yeast RAD6, rabbit E2(14k), and the human 17-kDa E2 as a subclass of E2s which biochemically support E3-mediated conjugation and ubiquitin-dependent proteolysis and physiologically play a role in DNA repair. PMID- 1313009 TI - Putative inositol 1,4,5-trisphosphate binding proteins in rat brain cytosol. AB - In previous works, we synthesized a series of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) analogs, with a substituent on the second carbon of the inositol ring. Using these analogs, the Ins(1,4,5)P3 affinity media were also synthesized (Hirata, M., Watanabe, Y., Ishimatsu, T., Yanaga, F., Koga, T., and Ozaki, S. (1990) Biochem. Biophys. Res. Commun. 168, 379-386). When the cytosol fraction from the rat brain was applied to an Ins(1,4,5)P3 affinity column, an eluate with a 2 M NaCl solution was found to have remarkable Ins(1,4,5)P3-binding activity. The active fraction was further fractionated with gel filtration chromatography, and two proteins with an apparent molecular mass of 130 or 85 kDa were found to be Ins(1,4,5)P3-binding proteins but with no Ins(1,4,5)P3 metabolizing activities. Partial amino acid sequences determined after proteolysis and reversed-phase chromatography revealed that the protein with an apparent molecular mass of 85 kDa is the delta-isozyme of phospholipase C and that of 130 kDa has no sequence the same as the Ins(1,4,5)P3-recognizing proteins hitherto examined. Ins(1,4,5)P3 at concentrations greater than 1 microM strongly inhibited 85-kDa phospholipase C delta activity, without changing its dependence on the concentrations of free Ca2+ and H+. Among inositol phosphates examined, Ins(3,4,5,6)P4 inhibited the binding of [3H]Ins(1,4,5)P3 to the 130-kDa protein at much the same concentrations as seen with Ins(1,4,5)P3. This report seems to be the first evidence for the presence of soluble Ins(1,4,5)P3-binding proteins in the rat brain, one of which is the delta isozyme of phospholipase C. PMID- 1313010 TI - Lysine 274 is essential for fructose 2,6-bisphosphate inhibition of fructose-1,6 bisphosphatase. AB - Lysine 274 is conserved in all known fructose-1,6-bisphosphatase sequences. It has been implicated in substrate binding and/or catalysis on the basis of reactivity with pyridoxal phosphate as well as by x-ray crystallographic analysis. Lys274 of rat liver fructose-1,6-bisphosphatase was mutated to alanine by the polymerase chain reaction, and the T7-RNA polymerase-transcribed construct containing the mutant sequence was expressed in Escherichia coli. The mutant and wild-type forms of the enzyme were purified to homogeneity, and their specific activity, substrate dependence, and inhibition by fructose 2,6-bisphosphate and AMP were compared. While the mutant exhibited no change in maximal velocity, its Km for fructose 1,6-bisphosphate was 20-fold higher than that of the wild-type, and its Ki for fructose 2,6-bisphosphate was increased 1000-fold. Consistent with the unaltered maximal velocity, there were no apparent difference between the secondary structure of the wild-type and mutant enzyme forms, as measured by circular dichroism and ultraviolet difference spectroscopy. The Ki for the allosteric inhibitor AMP was only slightly increased, indicating that Lys274 is not directly involved in AMP inhibition. Fructose 2,6-bisphosphate potentiated AMP inhibition of both forms, but 500-fold higher concentrations of fructose 2,6 bisphosphate were needed to reduce the Ki for AMP for the mutant compared to the wild-type. However, potentiation of AMP inhibition of the Lys274----Ala mutant was evident at fructose 2,6-bisphosphate concentrations (approximately 100 microM) well below those that inhibited the enzyme, which suggests that fructose 2,6-bisphosphate interacts either with the AMP site directly or with other residues involved in the active site-AMP synergy. The results also demonstrate that although Lys274 is an important binding site determinant for sugar bisphosphates, it plays a more significant role in binding fructose 2,6 bisphosphate than fructose 1,6-bisphosphate, probably because it binds the 2 phospho group of the former while other residues bind the 1-phospho group of the substrate. It is concluded that the enzyme utilizes Lys274 to discriminate between its substrate and fructose 2,6-bisphosphate. PMID- 1313011 TI - Isolation, characterization, and amino acid sequences of auracyanins, blue copper proteins from the green photosynthetic bacterium Chloroflexus aurantiacus. AB - Three small blue copper proteins designated auracyanin A, auracyanin B-1, and auracyanin B-2 have been isolated from the thermophilic green gliding photosynthetic bacterium Chloroflexus aurantiacus. All three auracyanins are peripheral membrane proteins. Auracyanin A was described previously (Trost, J. T., McManus, J. D., Freeman, J. C., Ramakrishna, B. L., and Blankenship, R. E. (1988) Biochemistry 27, 7858-7863) and is not glycosylated. The two B forms are glycoproteins and have almost identical properties to each other, but are distinct from the A form. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis apparent monomer molecular masses are 14 (A), 18 (B-2), and 22 (B 1) kDa. The amino acid sequences of the B forms are presented. All three proteins have similar absorbance, circular dichroism, and resonance Raman spectra, but the electron spin resonance signals are quite different. Laser flash photolysis kinetic analysis of the reactions of the three forms of auracyanin with lumiflavin and flavin mononucleotide semiquinones indicates that the site of electron transfer is negatively charged and has an accessibility similar to that found in other blue copper proteins. Copper analysis indicates that all three proteins contain 1 mol of copper per mol of protein. All three auracyanins exhibit a midpoint redox potential of +240 mV. Light-induced absorbance changes and electron spin resonance signals suggest that auracyanin A may play a role in photosynthetic electron transfer. Kinetic data indicate that all three proteins can donate electrons to cytochrome c-554, the electron donor to the photosynthetic reaction center. PMID- 1313012 TI - Glu327 is part of a catalytic triad in rat liver fructose-2,6-bisphosphatase. AB - The fructose-2,6-bisphosphatase domain of 6-phosphofructo-2-kinase/fructose-2,6 bisphosphatase has been shown to be structurally and functionally homologous to phosphoglycerate mutase. Both enzymes catalyze their reactions via phosphoenzyme intermediates which utilize an active site histidine as a nucleophilic phosphoacceptor and another histidine as a proton donor to the leaving group. Glu327 in the bisphosphatase domain of the rat liver bifunctional enzyme is conserved in all phosphoglycerate mutase structures and is postulated, by modelling studies, to be located in the active site. Glu327 was mutated to Ala, Gln, or Asp. The mutant and wild-type enzymes were expressed in Escherichia coli with a T-7 RNA polymerase-based expression system and purified to homogeneity by substrate elution from phosphocellulose. The Glu327 mutants had apparent molecular weights of 110,000 by gel filtration and had unaltered 6-phosphofructo 2-kinase activity. Circular dichroism showed that the secondary structure of the Glu327 mutant enzyme forms was the same as the wild-type enzyme. The maximal velocity of the fructose-2,6-bisphosphatase of the Glu327----Ala, Glu327----Gln, and Glu327----Asp mutants was 4, 2, and 20%, respectively, that of the wild-type enzyme, but the rate of phosphoenzyme formation of the mutants was reduced by at least a factor of 1000. In addition, the rate constants of phosphoenzyme hydrolysis for the Glu372----Ala and Glu327----Gln mutants were 2.7 and 1.3%, respectively, of the wild type, whereas the rate constant for the Glu327----Asp mutant was 60% of the wild-type value. Glu327 was not a substrate or product binding site determinant since the Km for fructose-2,6-bisphosphate and Ki for fructose-6-phosphate of the mutants were not appreciably changed. The results implicate Glu327 as part of a catalytic triad in fructose-2,6-bisphosphatase and suggest that it influences the protonation state of the active site histidine residues during phosphoenzyme formation and/or acts as a base catalyst to enhance the nucleophilic attack of water on the phosphoenzyme intermediate. PMID- 1313013 TI - Permissible amino acid substitutions within the putative nucleoside binding site of herpes simplex virus type 1 encoded thymidine kinase established by random sequence mutagenesis [corrected]. AB - We determined the essentiality of all amino acid replacements within an 11-codon sequence in the putative nucleoside-binding site of thymidine kinase encoded by herpes simplex virus type 1. This involved partial randomization of 11 codons in the gene to create a degenerate library, followed by genetic complementation using a tk- Escherichia coli strain and selection of unnatural active enzymes. We produced and tested 53,000 variants; of which 190 were found to be biologically active. Sequence analyses of functional variants revealed a high degree of flexibility in accommodating different types of amino acid substitutions in this region. However, no replacement was tolerated at proline-173, whereas tyrosine 172 could be replaced by only phenylalanine. To further define permissible substitutions at specified positions, we constructed a library with randomization at only four test codons. We produced and tested 600,000 variants; of which only 5 were active. Again proline-173 was conserved, and only tyrosine and phenylalanine were found at position 172. The identification of these conserved amino acids should provide important insights into the understanding of the structural basis of catalysis by this enzyme. PMID- 1313014 TI - The energy transduction mechanism is different among P-type ion-transporting ATPases. Acetyl phosphate causes uncoupling between hydrolysis and ion transport in H+,K(+)-ATPase. AB - H+,K(+)-ATPase, Na+,K(+)-ATPase, and Ca(2+)-ATPase belong to the P-type ATPase group. Their molecular mechanisms of energy transduction have been thought to be similar until now. Ca(2+)-ATPase and Na+,K(+)-ATPase are phosphorylated from both ATP and acetyl phosphate (ACP) and dephosphorylated, resulting in active ion transport. However, we found that H+,K(+)-ATPase did not transport proton nor K+ when ACP was used as a substrate, resulting in uncoupling between energy and ion transport. ACP bound competitively to the ATP-binding site of H+,K(+)-ATPase. The hydrolysis of ACP by H+,K(+)-ATPase was stimulated by cytosolic K+, the half maximal stimulating K+ concentration (K0.5) being 2.5 mM, whereas the hydrolysis of ATP was stimulated by luminal K+, the K0.5 being 0.2 mM. Furthermore, during the phosphorylation from ACP in the absence of K+, the fluorescence intensity of H+,K(+)-ATPase labeled with fluorescein isothiocyanate increased, but those of Na+,K(+)-ATPase and Ca(2+)-ATPase decreased. These results indicate that phosphorylated intermediates of H+,K(+)-ATPase formed from ACP are not rich in energy and that there is a striking difference(s) in the mechanism of energy transduction between H+,K(+)-ATPase and other cation-transporting ATPases. PMID- 1313015 TI - Low affinity superphosphorylation of the Na,K-ATPase by ATP. AB - Pre-steady-state phosphorylation of purified Na,K-ATPase from red outer medulla of pig kidney was studied at 25 degrees C and an ample range of [tau-32P]ATP concentrations. At 10 microM ATP phosphorylation followed simple exponential kinetics reaching after 40 ms a steady level of 0.76 +/- 0.04 nmol of P/mg of protein with kapp = 73.0 +/- 6.5 s-1. At 500 microM ATP the time course of phosphorylation changed drastically, since the phosphoenzyme reached a level two to four times higher at a much higher rate (kapp greater than or equal to 370 s 1) and in about 40 ms dropped to the same steady level as with 10 microM ATP. This superphosphorylation was not observed in Na,K-ATPase undergoing turnover in a medium with Mg2+, Na+, and ATP, suggesting that it required the enzyme to be at rest. Superphosphorylation depended on Mg2+ and Na+ and was fully inhibited by ouabain and FITC. After denaturation the phosphoenzyme made by superphosphorylation had the electrophoretic mobility of the alpha-subunit of the Na,K-ATPase, and its hydrolysis was accelerated by hydroxylamine. On a molar basis, the stoichiometry of phosphate per ouabain bound was 2.40 +/- 0.60 after phosphorylation with 1000 microM ATP. The results are consistent with the idea that under proper conditions every functional Na,K-ATPase unit can accept two, or more, phosphates of rapid turnover from ATP. PMID- 1313017 TI - Activated cGMP phosphodiesterase of retinal rods. A complex with transducin alpha subunit. AB - Purified G-protein (transducin) activated with the nonhydrolyzable analog guanosine 5'-O-(thiotriphosphate) (GTP gamma S) and cGMP phosphodiesterase (PDE) from retinal rods are added to protein-stripped disc membranes. Specific binding of the mainly soluble alpha subunit of G-protein with GTP gamma S bound (G alpha GTP gamma S, activator of the PDE) to the disc membrane in the presence of PDE is measured from gel scans or experiments with labeled G-protein alpha subunit (G alpha). Its variation as a function of G concentration matches the theoretical variation of G alpha involved in the activation of PDE calculated with previously estimated dissociation constants (Bennett, N., and Clerc, A. (1989) Biochemistry 28, 7418-7424), and the G alpha bound/PDE ratio at saturation is close to 2. No increase of G alpha binding to the membrane is observed when purified inhibitory subunit of PDE (PDE gamma) is added together with or instead of total PDE, and excess PDE gamma remains soluble. These results suggest that activated PDE is a complex with the activator G alpha GTP rather than PDE from which the inhibitory subunits have been removed. A method for purifying PDE gamma with a high yield of recovery and activity is described. PMID- 1313016 TI - Dual regulation of arachidonic acid release by P2U purinergic receptors in dibutyryl cyclic AMP-differentiated HL60 cells. AB - ATP promoted biphasic effects on both basal and fMLP-stimulated arachidonic acid (AA) release in neutrophil-like HL60 cells: stimulation in the micromolar range (EC50 = 3.2 +/- 0.9 microM) and inhibition at higher concentrations (EC50 = 90 +/ 11 microM). ATP also inhibited UTP- and platelet activating factor-stimulated AA release. Only stimulatory effects of ATP on basal or fMLP-stimulated phospholipase C were observed. The inhibitory effect of ATP on AA release was not due to reacylation of released AA, chelation of extracellular Ca2+, cell permeabilization, or changes in the rise of [Ca2+]i induced by agonist. The inhibition was rapid, being detected within 5-15 s. The inhibitory effect of ATP on fMLP-stimulated AA release could be desensitized by pretreatment of the cells with 2 mM ATP, but not 20 microM ATP, the concentration that resulted in maximal release of AA and inositol phosphates. The inhibition by ATP was neither dependent on generation of adenosine by ATP hydrolysis nor the result of direct interaction of ATP with P1 purinergic receptors. Among other nucleotides tested (CTP, GTP, ITP, TTP, XTP, adenosine 5'-(beta,gamma-methylene)triphosphate (AMP PCP), adenyl-5'-yl imidodiphosphate (AMP-P(NH)P), ADP, adenosine 5'-O-(3 thiotriphosphate) (ATP gamma S), and UTP), only UTP and ATP gamma S displayed biphasic effects with potencies and efficacies almost identical to those of ATP. The other nucleotides only exhibited stimulatory effects (EC50 = 60-300 microM). The results are consistent with a model of dual regulation of AA release by two distinct subtypes of P2U receptors in HL60 cells. PMID- 1313018 TI - Mapping the site(s) of MgATP and MgADP interaction with the nitrogenase of Azotobacter vinelandii. Lysine 15 of the iron protein plays a major role in MgATP interaction. AB - Nitrogenase binds and hydrolyzes 2MgATP yielding 2MgADP and 2Pi for each electron that is transferred from the iron protein to the MoFe protein. The iron protein alone binds but does not hydrolyze 2MgATP or 2MgADP and the binding of these nucleotides is competitive. Iron protein amino acid sequences all contain a putatitive mononucleotide-binding region similar to a region found in other mononucleotide-binding proteins. To examine the role of this region in MgATP interaction, we have substituted glutamine and proline for conserved lysine 15. The amino acid substitutions, K15Q and K15P, both yielded a non-N2-fixing phenotype when the genes coding for them were substituted into the Azotobacter vinelandii chromosome in place of the wild-type gene. The iron protein from the K15Q mutant was purified to homogeneity, whereas the protein from the K15P mutant could not be purified in its native form. Unlike wild-type iron protein, the purified K15Q iron protein showed no acetylene reduction, H2 evolution, or ATP hydrolysis activities when complemented with wild-type MoFe protein. The K15Q iron protein and the normal iron protein had a similar total iron content and both proteins showed the characteristic rhombic EPR signal resulting from the reduced state of the single 4Fe-4S cluster bridging the two subunits. Unlike the wild-type iron protein, addition of MgATP to the K15Q iron protein did not result in the perturbation necessary to change the EPR signal of its 4Fe-4S center from a rhombic to an axial line shape. Also unlike the wild-type iron protein, addition of MgATP to K15Q iron protein in the presence of the iron chelator, alpha,alpha'-dipyridyl, did not result in a time-dependent transfer of iron to the chelator. Thus, even though the K15Q iron protein contains a normal 4Fe-4S center, it does not respond to MgATP like the wild-type protein. Examination of the ability of the K15Q iron protein to bind MgADP showed no change from the wild type iron protein, but its ability to bind MgATP decreased to 35% of the wild type protein. Thus, in A. vinelandii iron protein, lysine 15 is not needed for interaction with MgADP but is involved in the binding of ATP, presumably through charge-charge interaction with the gamma-phosphate. Based on the above data, this lysine appears to be essential for the MgATP induced conformational change of wild-type iron protein that is required for activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1313020 TI - Hexadecylphosphocholine inhibits translocation of CTP:choline-phosphate cytidylyltransferase in Madin-Darby canine kidney cells. AB - The mechanism of the inhibition of phosphatidylcholine biosynthesis by the phospholipid analogue, hexadecylphosphocholine, was investigated in Madin-Darby canine kidney cells. In the presence of 50 mumol/liter hexadecylphosphocholine, there was a translocation of CTP:choline-phosphate cytidylyltransferase (EC 22.7.7.15) activity from the membranes to the cytosol of the cells. Since we recently demonstrated that hexadecylphosphocholine also inhibits protein kinase C in vitro, [methyl-3H]choline labeling experiments were repeated with phorbol ester-desensitized cells. In these cells the same inhibitory effect of hexadecylphosphocholine was measured. As a consequence of inhibition, the [methyl 3H]choline incorporation into the phosphocholine pool was increased time dependently. In addition, there was no evidence for a difference between the choline uptake of control and hexadecylphosphocholine-treated cells. Likewise, the amount of diacylglycerol, a known activator of the translocation process, was not reduced. Finally, we showed that the inhibitory effect of hexadecylphosphocholine on CTP:choline-phosphate cytidylyltransferase translocation cannot be explained by the detergent properties of this phospholipid analogue. Therefore, we suggest a direct inhibitory effect of hexadecylphosphocholine on the translocation of CTP:choline-phosphate cytidylyltransferase. PMID- 1313019 TI - [3H]ryanodine as a probe of changes in the functional state of the Ca(2+)-release channel in malignant hyperthermia. AB - The defect in malignant hyperthermia (MH) alters the binding of [3H]ryanodine to the Ca(2+)-release channel by increasing its apparent affinity for the binding site. In sarcoplasmic reticulum (SR) membranes from both normal and mutant pigs the apparent Kd is dependent on a number of parameters. Adenosine 5'-(beta,gamma methylene)triphosphate, ionic strength, and Ca2+ each increase the apparent affinity of the binding site for [3H]ryanodine. Equilibrium and kinetic evaluation of the binding of [3H]ryanodine to these membranes demonstrates that the MH defect in pigs increases the apparent affinity of the membranes for [3H]ryanodine by increasing the amount of high affinity relative to low affinity binding sites. Both the association and dissociation of [3H]ryanodine with all three types of membranes (normal, heterozygous MH, homozygous MH) are characterized by two or more components, with the relative ratios of these components altered by the MH defect. These findings suggest that the observed Kd is the weighted average of the binding of ryanodine to two or more interconvertible states of the channel. Dilution of [3H]ryanodine bound to normal membranes at high Ca2+ into low Ca2+ solutions enhances the rate of dissociation. This conversion occurs to a much lesser extent with MH membranes, suggesting that the MH defect may alter the rate at which the high affinity form of the protein converts to the low affinity form. PMID- 1313021 TI - Alanine scanning mutagenesis and functional analysis of the fibronectin-like collagen-binding domain from human 92-kDa type IV collagenase. AB - The human 72-kDa (CLG4A) and 92-kDa (CLG4B) type IV collagenases contain a domain consisting of three contiguous copies of the fibronectin (FN)-derived type II homology unit (T2HU), T2HU-1, T2HU-2, and T2HU-3. To investigate the functional role of this domain, we have constructed plasmids expressing beta-galactosidase fusion proteins with one or more of the CLG4B-derived T2HU. The gelatin binding assays demonstrate that a single copy of T2HU-2 renders beta-galactosidase capable of binding gelatin. The three repeats, however, differ dramatically in their capacity to bind gelatin, with T2HU-1 and T2HU-3 having significantly less binding activity than T2HU-2. Using alanine scanning mutagenesis we have defined the amino acid residues (Arg307, Asp309, Asn319, Tyr320, Asp323) that are critical for gelatin binding of T2HU-2. The low gelatin binding of T2HU-1 compared to T2HU-2 was traced to the non-conserved residues Ala228-Ala and Leu253 Pro. The results suggest that the gelatin binding of the type IV collagenase proenzyme is mediated by the FN-like domain, although the presence of another gelatin-binding site cannot be excluded. The FN domain-mediated binding, however, is not a rate-limiting step in the hydrolysis of gelatin by the enzyme. PMID- 1313022 TI - Synergistic interaction between the probucol phenoxyl radical and ascorbic acid in inhibiting the oxidation of low density lipoprotein. AB - Chain-breaking antioxidants such as butylated hydroxytoluene, alpha-tocopherol, and probucol have been shown to decrease markedly the oxidative modification of low density lipoprotein (LDL). Their mechanism of action appears to involve scavenging of LDL-lipid peroxyl radicals. The purpose of this study was to investigate the occurrence of radical reactions produced during oxidation of LDL and LDL-containing probucol initiated by lipoxygenase or copper. In addition, we have investigated the possibility of a synergistic interaction between ascorbate and probucol in inhibiting the oxidation of LDL. Incubation of LDL-containing probucol and lipoxygenase produced a composite electron spin resonance (ESR) spectrum due to the endogenous alpha-tocopheroxyl radical and probucol-derived phenoxyl radical. The spectral assignment was further verified by chemical oxidation of alpha-tocopherol and probucol. In the presence of ascorbic acid, these radicals in the LDL particle were reduced to their parent compounds with concomitant formation of the ascorbate radical. In both the peroxidation of linoleic acid and the copper-initiated peroxidation of LDL, the antioxidant activity of probucol was significantly increased by low (3-6 microM) concentrations of ascorbate. The probucol-dependent inhibition of LDL oxidation was enhanced in the presence of ascorbic acid. We conclude that the reaction between the phenoxyl radical of probucol and ascorbate results in a synergistic enhancement of the antioxidant capacity of these two compounds and speculate that such reactions could play a role in maintaining the antioxidant status of LDL during oxidative stress in vivo. PMID- 1313023 TI - Protein-DNA interactions at a dioxin-responsive enhancer. Mutational analysis of the DNA-binding site for the liganded Ah receptor. AB - The liganded Ah receptor activates transcription by binding to a specific DNA recognition motif within a dioxin-responsive enhancer upstream of the CYP1A1 gene. Analyses of mutant enhancers by gel retardation reveal that each base pair within the domain 5'CGTG(GCAC)3' is essential to the receptor-enhancer interaction. The three base pairs immediately flanking each end of the essential domain contribute less strongly to receptor binding. Analyses of enhancer function by transfection reveal that a mutation in the essential domain, which abolishes receptor-DNA binding, obliterates enhancer function. Mutations outside the essential domain, which diminish, but do not abolish, receptor-DNA binding, also obliterate enhancer function. Additionally, one mutation adjacent to the essential binding motif does not affect receptor-DNA binding, but destroys enhancer activity. These findings imply that transcriptional enhancement by the dioxin-responsive system cannot be predicted solely by the strength of the receptor-enhancer interaction. PMID- 1313024 TI - Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling. AB - Oxidation and redox cycling of the hydroxylated metabolites of the antimalarial drug primaquine (i.e. 5-hydroxyprimaquine, 5-hydroxydemethylprimaquine, and 5,6 dihydroxy-8-aminoquinoline) were studied. The three metabolites readily oxidized under physiological conditions, forming hydrogen peroxide and the corresponding quinone-imine derivatives as the main products. The latter compounds were characterized by visible, NMR, and infrared spectroscopy. Concomitant formation of drug-derived radicals and hydroxyl radicals was attested by direct and spin trapping EPR experiments, respectively. The use of the spin stabilization method indicated that the radicals derived from 5-hydroxydemethylprimaquine and 5,6 dihydroxy-8-aminoquinoline are of the o-semiquinone type. Tentative structures are proposed for the radicals based on product identification and computer simulation of the experimental EPR spectra. The quinone-imines obtained from the reduced metabolites did not react at appreciable rates with NADPH but underwent redox cycling upon addition of ferredoxin:NADP+ oxidoreductase, forming hydrogen peroxide and hydroxyl radicals. The effect of antioxidant enzymes on hydroxyl radical yield obtained during oxidation and redox cycling indicates that the main route for hydroxyl radical formation is the metal ion-catalyzed reaction between the drug-derived radicals and hydrogen peroxide. Taken together, the results indicate that hydrogen peroxide is the potential toxic product formed from the primaquine metabolites. PMID- 1313025 TI - Dioxin- and Ah receptor-dependent protein binding to xenobiotic responsive elements and G-rich DNA studied by in vivo footprinting. AB - DNA-protein interactions before and after transcriptional activation of the carcinogen- and dioxin-inducible enhancer of the murine CYP1A1 gene were detected in vivo by treatment with dimethyl sulfate followed by ligation-mediated, polymerase chain reaction-aided genomic sequencing. Following 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) treatment of mouse Hepa-1 hepatoma cells, evidence of protein binding was detected at the sequence 5' CACGCNA/T 3' within two previously defined xenobiotic response elements (XREs). The observed XRE footprint was similar to that previously identified by in vitro methylation protection footprints and attributed to the binding protein for 2,3,7,8 tetrachlorodibenzo-p-dioxin the Ah receptor. No XRE footprinting was observed in Hepa-1 mutant cells possessing a defective Ah receptor. Unexpectedly, evidence of protein binding was also detected at a G-rich DNA sequence immediately adjacent to one of the XREs. Footprinting of the G-rich sequence element, like that of XRE1 and XRE2, was dependent on the presence of a functional Ah receptor. The Ah receptor is therefore able to bind to its own DNA target sites in vivo and is also required for the binding of a second factor to the G-rich element. PMID- 1313026 TI - ATPase-deficient mutants of the Escherichia coli DNA replication protein PriA are capable of catalyzing the assembly of active primosomes. AB - The PriA replication protein of Escherichia coli (formerly replication factor Y or protein n') is multifunctional. It is a site-specific, single-stranded DNA dependent ATPase (dATPase), a 3'----5' DNA helicase, and guides the ordered assembly of the primosome, a mobile, multiprotein DNA replication priming/helicase complex. Although PriA is not absolutely required for viability, priA null mutant cells grow very slowly, have poor viability, and form extensive filaments. In order to assess which of the multiple activities of PriA are required for normal replication and growth, site-directed mutagenesis was employed to introduce single amino acid substitutions for the invariant lysine within the consensus nucleotide-binding motif found in PriA. Biochemical characterization of the representative purified mutant PriA proteins revealed them to be completely deficient in nucleotide hydrolysis, incapable of translocation along a single-stranded DNA binding protein-coated single-stranded DNA template, and unable to manifest the 3'----5' DNA helicase activity of wild type PriA. These mutant proteins were, however, capable of catalyzing the assembly of active primosomes in vitro. Furthermore, when supplied in trans to insertionally inactivated priA cells, plasmids containing a copy of these mutant priA genes restored the wild-type growth rate, viability, and cell morphology. Based on these results, a model for PriA function in vivo is discussed. PMID- 1313027 TI - Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin. AB - The carbohydrate binding specificity of Mr = 30,000 lectin (CBP30) from baby hamster kidney (BHK) cells has been studied by inhibition of binding of the radiolabeled lectin to asialofetuin-Sepharose using model oligosaccharides and glycopeptides. CBP30 binds type I or II Gal beta(1----3(4))GlcNAc chains but not Gal(beta 1----3)GalNAc. The inhibitory potency of straight chain polylactosamine structures or complex-type branched glycans is increased in proportion to the number of Gal(beta 1----3(4)) units present. Fucosylation or sialylation of terminal galactose residues or further substitution by (alpha 1----3)-linked galactose or N-acetylgalactosamine does not affect binding whereas substitution of the penultimate N-acetylglucosamine residue drastically reduces binding. Thus, blood group A, H type I or H type II structures, shows high affinity whereas Lex, Lea, and Leb structures bind poorly. CBP30 binds to murine Engelbreth-Holm-Swarm (EHS) tumor laminin and human amniotic fluid fibronectin but not human plasma fibronectin. Binding involves polylactosamine glycans as well as tri- and tetraantennary complex-type glycans present in EHS laminin and amniotic fluid fibronectin but absent in plasma fibronectin. Proteolytic fragments of EHS laminin (E1X/Nd, P1, E8, and E3) bind CBP30, but only fragment E8 supports attachment and spreading of BHK cells. BHK cell adhesion to EHS laminin or fragment E8 was not disturbed by CBP30-specific antibodies, but at relatively high concentrations (45 micrograms/ml) CBP30 inhibited spreading and partially attachment of cells on laminin. PMID- 1313028 TI - Phorbol esters inhibit the dioxin receptor-mediated transcriptional activation of the mouse Cyp1a-1 and Cyp1a-2 genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - Tetradecanoyl phorbol acetate (TPA) has been shown to inhibit 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-induced mouse P450IA1 benzo[a]pyrene hydroxylase activity (Raunio, H., and Pelkonen, O. (1983) Cancer Res. 43, 782 786). When we co-administered TPA and TCDD to C57BL/6 mice, the accumulation of TCDD-inducible liver P450IA1 and P450IA2 mRNA, as well as kidney P450IA1 mRNA, was greatly inhibited. When nuclear run-on assays were conducted, maximal levels of transcriptional activation were achieved for both liver Cyp1a-1 and Cyp1a-2 with 1 micrograms/kg (approximately equal to 3.0 nmol/kg) TCDD. TCDD elicited a dose-dependent increase in the rates of gene transcription, which paralleled the induction of P450IA1 and P450IA2 mRNA. Only Cyp1a-1 gene transcription was elevated in kidney. When these experiments were repeated following the co administration of TPA with TCDD, the levels of TCDD-mediated transcriptional increases in liver Cyp1a-1 and Cyp1a-2 and P450IA1 and P450IA2 mRNAs were dramatically inhibited. The reduction in Cyp1a gene transcription by TPA could be accounted for by reduced DNA binding of the dioxin receptor to the xenobiotic responsive element (XRE) sequences, as measured by gel-retardation analysis. Analysis of nuclear [3H]TCDD dioxin receptor by sucrose density gradients demonstrated that the inhibition of Cyp1a gene transcription and DNA binding by TPA resulted from a reduction in nuclear dioxin receptor concentration. PMID- 1313029 TI - Cyclic AMP acutely stimulates translocation of the major insulin-regulatable glucose transporter GLUT4. AB - Facilitated glucose transport across plasma membranes is mediated by a family of transporters (GLUT1-GLUT5) that have different tissue distributions and Km values for transport. It has been shown that insulin stimulates glucose transport in fat and muscle tissues by causing the redistribution of one of these proteins (GLUT4) from inside the cell to the plasma membrane. Previous studies have shown that agents that change cAMP levels are able to modulate glucose transport in fat cells. The aim of this study was to investigate the mechanisms responsible for modulation of glucose transport by cAMP. 2-Deoxyglucose transport and insulin regulatable glucose transporter (GLUT4) immunoreactivity in plasma and low density microsomal membranes were measured in adipocytes incubated for 30 min with insulin or dibutyryl-cAMP (Bt2cAMP). Low concentrations of Bt2cAMP (10 microM) increased 2-deoxyglucose uptake by translocating GLUT4 from low density microsomal membranes to the plasma membranes. Bt2cAMP at 1000 microM inhibited glucose transport below basal but further increased translocation of GLUT4. The effect of Bt2cAMP on translocation was additive to that of 7 nM insulin. We conclude that in rat adipocytes, Bt2cAMP acutely translocates GLUT4 but inhibits its activity to transport glucose. PMID- 1313030 TI - Autophosphorylation of inositol 1,4,5-trisphosphate receptors. AB - Inositol 1,4,5-trisphosphate (IP3) releases internal stores of calcium by binding to a specific membrane receptor which includes both the IP3 recognition site as well as the associated calcium channel. The IP3 receptor is regulated by ATP, calcium, and phosphorylation by protein kinase A, protein kinase C, and calcium/calmodulin-dependent protein kinase II. Its cDNA sequence predicts at least two consensus sequences where nucleotides might bind, and direct binding of ATP to the IP3 receptor has been demonstrated. In the present study, we demonstrate autophosphorylation of the purified and reconstituted IP3 receptor on serine and find serine protein kinase activity of the IP3 receptor toward a specific peptide substrate. Several independent purification procedures do not separate the IP3 receptor protein from the phosphorylating activity, and many different protein kinase activators and inhibitors do not identify protein kinases as contaminants. Also, renaturation experiments reveal autophosphorylation of the monomeric receptor on polyvinylidene difluoride membranes. PMID- 1313031 TI - Inhibition of tissue kallikrein by protein C inhibitor. Evidence for identity of protein C inhibitor with the kallikrein binding protein. AB - We studied the inhibition of tissue kallikrein by protein C inhibitor (PCI), a relatively unspecific heparin-dependent serine protease inhibitor present in plasma and urine. PCI inhibited the amidolytic activity (cleavage of H-D-valyl-L leucyl-arginine-p-nitroaniline) of urinary kallikrein with an apparent second order rate constant of 2.3 x 10(4) M-1 s-1 and formed stable complexes (85 kDa) with urinary kallikrein as judged from silver-stained sodium dodecyl sulfate polyacrylamide gels. Complex formation was time-dependent and was paralleled by a decrease in the intensity of the main PCI protein band (Mr = 57,000) and an increase in the intensity of the lower Mr (54,000) PCI form (cleaved inhibitor). Heparin interfered with the inhibition of tissue kallikrein by PCI and with the formation of tissue kallikrein-PCI complexes in a dose-dependent fashion and completely abolished PCI-tissue kallikrein interaction at 300 micrograms/ml. This is in contrast to findings on the interaction of PCI with all other target proteases studied so far (i.e. stimulation of inhibition by heparin) but is similar to the reaction pattern of 125I-labeled tissue kallikrein with so called kallikrein binding protein described in serum and other systems. To study a possible relationship between PCI and this kallikrein binding protein we incubated 125I-labeled urinary kallikrein in serum and in PCI-immunodepleted serum in the absence and presence of heparin and analyzed complex formation using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In normal serum, formed complexes co-migrated with complexes of purified PCI and 125I-kallikrein and were less intense in the presence of heparin. No complex formation at all was seen in PCI-depleted serum. Our data indicate that PCI may be a physiologically important endogenous inhibitor of tissue kallikrein and provide evidence that PCI may be identical to the previously described kallikrein binding protein. PMID- 1313032 TI - A novel intermediate in processing of murine leukemia virus envelope glycoproteins. Proteolytic cleavage in the late Golgi region. AB - The intracellular processing of the murine leukemia virus envelope glycoprotein precursor Pr85 to the mature products gp70 and p15e was analyzed in the mouse T lymphoma cell line W7MG1. Kinetic (pulse-chase) analysis of synthesis and processing, coupled with endoglycosidase (endo H) and neuraminidase digestions revealed the existence of a novel high molecular weight processing intermediate, gp95, containing endo H-resistant terminally glycosylated oligosaccharide chains. In contrast to previously published conclusions, our data indicate that proteolytic cleavage of the envelope precursor occurs after the acquisition of endo H-resistant chains and terminal glycosylation and thus after the mannosidase II step. In the same W7MG1 cell line, the type and order of murine leukemia virus envelope protein processing events was identical to that for the mouse mammary tumor virus envelope protein. Interestingly, complete mouse mammary tumor virus envelope protein processing requires the addition of glucocorticoid hormone, whereas murine leukemia virus envelope protein processing occurs constitutively in these W7MG1 cells. We propose that all retroviral envelope proteins share a common processing pathway in which proteolytic processing is a late event that follows acquisition of endo H resistance and terminal glycosylation. PMID- 1313033 TI - Ligand specificity of human thrombomodulin. Equilibrium binding of human thrombin, meizothrombin, and factor Xa to recombinant thrombomodulin. AB - Thrombomodulin is an endothelial glycoprotein that serves as a cofactor for protein C activation. To examine the ligand specificity of human thrombomodulin, we performed equilibrium binding assays with human thrombin, thrombin S205A (wherein the active site serine is replaced by alanine), meizothrombin S205A, and human factor Xa. In competition binding assays with CV-1(18A) cells expressing cell surface recombinant human thrombomodulin, recombinant wild type thrombin and thrombin S205A inhibited 125I-diisopropyl fluorophosphate-thrombin binding with similar affinity (Kd = 6.4 +/- 0.5 and 5.3 +/- 0.3 nM, respectively). However, no binding inhibition was detected for meizothrombin S205A or human factor Xa (Kd greater than 500 nM). In direct binding assays, 125I-labeled plasma thrombin and thrombin S205A bound to thrombomodulin with Kd values of 4.0 +/- 1.9 and 6.9 +/- 1.2 nM, respectively. 125I-Labeled meizothrombin S205A and human factor Xa did not bind to thrombomodulin (Kd greater than 500 nM). We also compared the ability of thrombin and factor Xa to activate human recombinant protein C. The activation of recombinant protein C by thrombin was greatly enhanced in the presence of thrombomodulin, whereas no significant activation by factor Xa was detected with or without thrombomodulin. Similar results were obtained with thrombin and factor Xa when human umbilical vein endothelial cells were used as the source of thrombomodulin. These results suggest that human meizothrombin and factor Xa are unlikely to be important thrombomodulin-dependent protein C activators and that thrombin is the physiological ligand for human endothelial cell thrombomodulin. PMID- 1313034 TI - Identification and partial characterization of two classes of receptors for human hepatocyte growth factor on adult rat hepatocytes in primary culture. AB - To characterize the receptor(s) for human hepatocyte growth factor (hHGF), a physiological hepatotrophic factor involved in liver regeneration following hepatic injury, recombinant hHGF (rhHGF) was radioiodinated. The labeled rhHGF retained its full biological activity on adult rat hepatocytes in primary culture. The specific binding of [125I]iodo-rhHGF to hepatocytes reached a plateau within 240 min at 4 degrees C. Scatchard plot analysis of the binding data suggested the presence of two classes of high affinity binding sites for [125I]iodo-rhHGF. One of the sites had a dissociation constant (Kd) of about 4.6 pM with 300 sites/cell and the other has a Kd of about 275 pM with 15,160 sites/cell. Unlabeled rhHGF displaced cell surface-bound [125I]iodo-rhHGF in a dose-dependent manner as did native hHGF purified from plasma of patients with fulminant hepatic failure. However, other growth factors to rat hepatocytes in primary culture such as insulin and human epidermal growth factor, and proteins which have high amino acid sequence-homology to hHGF such as plasminogen and prothrombin, did not compete with [125I]iodo-rhHGF in the binding, which suggests the binding was specific to hHGF. Covalent cross-linking experiment of [125I]iodo rhHGF to cell surface receptor(s) on hepatocytes showed there were two macromolecular species with apparent molecular weights of 330,000 and 230,000. Unlabeled rhHGF and native hHGF competed for the binding of [125I]iodo-rhHGF to the two macromolecular species, but insulin, human epidermal growth factor, plasminogen, and prothrombin did not. Based upon our estimated molecular weight of rhHGF = 84,000, these results suggest that hHGF specifically binds to two polypeptides of 246,000 and 146,000 daltons which are likely to represent the hHGF receptors of primary cultured rat hepatocytes. PMID- 1313035 TI - The effect of low density lipoproteins, cholesterol, and 25-hydroxycholesterol on apolipoprotein B gene expression in HepG2 cells. AB - The purpose of the present study was to examine the effects of exogenous cholesterol on the apolipoprotein (Apo) B gene expression in HepG2 cells. Pure cholesterol had no significant effect on either the cellular content of cholesteryl esters or the net accumulation of neutral lipids and ApoB in the culture medium. By contrast, addition of 25-hydroxycholesterol increased the net accumulation of cholesteryl esters in cells and medium by 2-3-fold and decreased that of unesterified cholesterol by 50% in both compartments. A 33% reduction in the cellular content of triglycerides was commensurate with a 40% increase in their accumulation in the medium. A significant 3-fold increase in the net accumulation of ApoB in the medium was predominantly due to enhanced secretion of newly synthesized ApoB as established by pulse-chase studies. The stimulation in ApoB secretion was accompanied by a 55% increase in cellular ApoB mRNA. Under these experimental conditions, the low density lipoprotein receptor activity was decreased by only 12-20%. Addition of progesterone prevented the effects of 25 hydroxycholesterol. The changes in the concentration of neutral lipids and ApoB were reflected in the composition of secreted "low-density" lipoproteins. These particles had increased percentage contents of cholesteryl esters and ApoB and a decreased percentage content of unesterified cholesterol in comparison with lipoproteins produced by control cells. The rate of ApoB production was not correlated with the triglyceride mass in the cells but was positively correlated with the cellular and secreted cholesteryl esters and secreted triglycerides. With the exception of unchanged cellular unesterified cholesterol and ApoB mRNA levels, plasma low density lipoprotein had similar, although less pronounced, effects on the production of neutral lipids and ApoB. These results demonstrate that in HepG2 cells the synthesis and secretion of ApoB and cholesteryl esters are tightly coupled and that 25-hydroxycholesterol increased the concentration of ApoB-containing lipoproteins primarily by stimulating their production rather than reducing their catabolism. PMID- 1313036 TI - Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) on ganglionic transmission. AB - 1. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) caused blockade of ganglionic transmission as evidenced by a marked decrease of the amplitude of evoked post-ganglionic compound action potential of the isolated superior cervical ganglion of rat. 2. This effect was not related to its dopaminergic neurotoxicity since pretreatment with pargyline did not prevent the ganglion-blocking action of MPTP. The effects of MPTP on ganglionic transmission were qualitatively similar to those of its narcotic analgesic analogue meperidine. The effects of both drugs were antagonized by the narcotic antagonist naloxone, indicating that the ganglion-blocking effect of MPTP also involved opiate receptors. 3. Like meperidine and morphine, the ganglion-blocking action of MPTP was reduced when the concentration of Ca2+ in the Locke solution was elevated. The blocking effect of methadone on transmission was not reduced by naloxone or elevated Ca2+. 4. The effect of MPTP on nerve action potential was minimal, indicating that the drug blocked synaptic transmission in the ganglion. 5. These results suggest that MPTP inhibits synaptic transmission in the isolated superior cervical ganglion of the rat, probably by interfering with Ca2+ function. PMID- 1313037 TI - A simplified method for the detection of maedi-visna virus RNA by in situ hybridization. AB - A simplified in situ hybridization method for the detection of maedi-visna virus (MVV) RNA in cultured cells using 35S-labelled DNA probes is described. The protocol currently used in this laboratory for the in situ detection of MVV RNA involves paraformaldehyde fixation followed by extensive cellular pretreatment prior to hybridization. It was found that substitution of paraformaldehyde fixation with brief acetone treatment and the removal of subsequent pretreatment steps gave a similar level of hybridization signal to that of our standard protocol. Acetone fixed, non-pretreated samples were used to develop a double labelling procedure in which immunocytochemistry and in situ hybridization were combined to allow the simultaneous detection of visna virus antigens and RNA within the same cell. PMID- 1313038 TI - Colchicine treatment in the preparation of varicella-zoster virus inocula. AB - Two methods, ultrasonic and colchicine treatment, for preparing varicella-zoster virus (VZV) inocula were compared. Ultrasonic treatment was unsuccessful in achieving the release of detectable, infectious, cell-free VZV from infected human foreskin fibroblast (SF) cells. Sonication of infected SF cells resulted in losses of virus infectivity in direct correlation with losses in cell viability (r = 0.82). In the second method of generating VZV inocula, VZV-infected SF cells were treated for 15 min with 15-20 ng of colchicine per cell. Colchicine treatment maintained short-term survival of virus infectivity, but resulted in a dramatic decrease in long-term cell viability. In addition, colchicine-treated cells could not support the replication of VZV. PMID- 1313039 TI - A monoclonal antibody capture enzyme-linked immunosorbent assay for detecting antibodies to infectious bursal disease virus. AB - A monoclonal antibody capture enzyme-linked immunosorbent assay (mAb-ELISA) for antibodies to infectious bursal disease virus (IBDV) in chicken sera was developed and compared with conventional ELISA. When sera from farm chickens were tested by the two ELISAs and serum neutralization (SN), the correlation rate between SN and mAb-ELISA was 100% (49/49), and that between SN and conventional ELISA was 81.6% (40/49). In mAb-ELISA, all of the sera that were antibody negative by SN had low absorbance values (below 0.05), and the absorbance values correlated closely with the SN titers. In the conventional ELISA, however, the sera antibody-negative by SN had various absorbance values ranging from 0.06 to 0.32. mAb-ELISA had much lower non-specific reactions than the conventional ELISA against sera from IBD-negative chickens. PMID- 1313040 TI - A simple and rapid method of high quantity DNA isolation from cervical scrapes for detection of human papillomavirus infection. AB - Infection with human papillomavirus (HPV) is an important etiological factor in the development of cervical cancer, and detection of the viral genome is of prognostic importance, particularly for preneoplastic lesions. We developed a simple, easy and efficient non-organic method of DNA extraction from cervical scrapes for reliable detection of HPV DNA sequences. The method involves incubation of cell nuclei in higher concentration of proteinase K at 65 degrees C for 2.5 h. Following prolonged incubation at higher temperature, the enzyme is autoinactivated and the DNA isolated can be used directly for analysis without further purification. The recovery of DNA is more than 95% and it can be easily cleaved by restriction enzymes and is suitable for amplification by the polymerase chain reaction (PCR). The whole procedure is carried out in a single Eppendorf tube and a large number of specimens can be processed at a time without any error of handling. DNA extracted from a single smear sample is sufficient to conduct as many as four different molecular biology tests. This provides an opportunity for verification of sensitivity, specificity and reliability of each test for diagnosis of HPV infection without resorting to biopsy. PMID- 1313041 TI - Tn9 CAT gene contains a promoter for vaccinia virus transcription: implications for reverse-genetic techniques. AB - Vaccinia virus-dependent CAT expression was observed in virus-infected cells cotransfected with a promoterless CAT gene. Restriction endonuclease resection of the CAT plasmid indicated that expression was due to recognition by vaccinia virus RNA polymerase of sequences within the CAT gene itself, probably located within the 5' untranslated region of the gene. This observation is relevant to the design of reverse-genetic systems which use CAT as a reporter gene to detect replication of negative-strand RNA virus pseudogenomes. PMID- 1313042 TI - Lupus anti-DNA antibodies bearing the 8.12 idiotype appear to be somatically mutated. AB - Anti-DNA antibodies in systemic lupus erythematosus (SLE) sera were analyzed using an antiidiotype designated 8.12 which recognizes a determinant on lambda light chains highly expressed in SLE sera. Eight of ten normal individuals had peripheral blood lymphocytes which produced high-titered 8.12-positive antibodies, following transformation with Epstein Barr virus, implying that the 8.12-reactive sequence originates in the germline gene (GLG). Of 58 SLE sera, 32 contained elevated titers of 8.12-reactive antibodies. Twenty-three of these sera had 8.12-reactive anti-DNA antibodies, suggesting a strong correlation between 8.12 idiotype and DNA binding. Moreover, 20 of 26 8.12-reactive IgG antibodies and only 4 of 10 8.12-reactive IgM antibodies bound DNA (P less than 0.05). These observations strengthen our previous findings in myeloma sera that DNA binding is associated with IgG isotype in the 8.12 idiotype system and suggest that the acquisition of anti-DNA reactivity in antibodies bearing the GLG idiotype 8.12 is achieved by somatic mutation, a feature of an antigen-driven response. PMID- 1313043 TI - Cefamandole-susceptible strains of Legionella pneumophila serogroup 1: implications for diagnosis and utility as an epidemiological marker. AB - The standard selective Legionella medium that contains cefamandole failed to grow legionella pneumophila serogroup 1, subtype Bellingham, from a sputum sample from a patient with nosocomial Legionnaires' disease; the isolate did grow on a similar selective medium that substitutes vancomycin for cefamandole. Two Bellingham isolates from this patient's hospital environment also failed to grow when tested on the cefamandole medium. We tested 106 additional L. pneumophila serogroup 1 isolates that belonged to nine different monoclonal antibody subtypes and demonstrated that susceptibility to cefamandole was rare (10%) and limited to the Bellingham subtype. The diagnosis of Legionnaires' disease may be missed unless the culture protocol includes both a nonselective medium and a selective medium that does not contain cefamandole. In vitro susceptibility to cefamandole also provided an epidemiologic marker that linked a water source for a patient to nosocomial Legionnaires' disease. PMID- 1313044 TI - Comparison of sensitivities of three commercial MRC-5 cell lines grown in shell vials to cytomegalovirus and responses to enhancing agents. AB - MRC-5 cells grown in shell vials from three suppliers (Whittaker Bioproducts, Bartels, and ViroMed) were evaluated for sensitivity to human cytomegalovirus. Previous studies done in our laboratory showed that treatment of the cells with dexamethasone (DEX) and dimethyl sulfoxide (DMSO) or these agents plus calcium improved the sensitivity of cells from Whittaker. In this study, we compared the response of the Whittaker cells with those of the cells from Bartels and ViroMed, both treated and untreated, when tested with strain AD169, a strain of wild-type virus, and 41 clinical specimens from various sources. A progressive improvement in sensitivity to AD169 and the wild-type virus was seen for all cell lines with DEX-DSMO and DEX-DMSO-calcium treatments, although even untreated, the Whittaker cells were much more sensitive. Detection of most of the positive clinical specimens was enhanced by both treatments with the Whittaker cells. DEX-DMSO had little or no effect on Bartels or ViroMed cells, while DEX-DMSO-calcium usually effected some increase in the number of inclusions. Six specimens were recovered only on Whittaker cells. Protein studies were done on all groups to determine the effect, if any, of the treatments on the metabolism of the cells. PMID- 1313045 TI - Rapid method for epidemiological evaluation of gram-positive cocci by field inversion gel electrophoresis. AB - We report a rapid method for the isolation of intact chromosomal DNA from gram positive cocci that is suitable for in situ restriction endonuclease digestion in agarose blocks. When combined with a rapid field inversion gel electrophoresis protocol, this approach allows the preparation and electrophoretic analysis of chromosomal restriction fragments produced by rare-cutting enzymes in a total time period of 2 days from start to finish. The utility of the method is demonstrated in the epidemiological evaluation of Staphylococcus epidermidis clusters from two hospitals as well as of additional representative staphylococci and enterococci. PMID- 1313046 TI - Monoclonal antibody solution hybridization assay for detection of mouse hepatitis virus infection. AB - A monoclonal antibody solution hybridization (MASH) assay was developed to detect fecal excretion of mouse hepatitis virus (MHV). The assay used a biotinylated cDNA probe to detect viral RNA target sequences by hybridization in solution, capture of hybrids on the solid phase with antibiotin antibody, and immunoassay with an enzyme-labelled monoclonal antibody specific for DNA-RNA hybrids. The MASH assay was used to monitor the time course of enterotropic MHV excretion after oronasal inoculation. Infectivity of the inoculated mice was simultaneously monitored with sentinel animals. The MASH assay detected MHV excretion in all inoculated mice, with the highest mean excretion levels occurring from day 3 through day 9 postinoculation. Mean excretion then decreased gradually to below detection limits by day 21 postinoculation. Sentinels became infected on exposure to inoculated mice up to but not after day 21 postinoculation. Infected sentinel mice showed a time course of virus excretion similar to that of inoculated mice. These results indicate that the MASH assay is useful for rapid, sensitive, and specific detection of MHV in clinical specimens from laboratory mice. PMID- 1313047 TI - Early detection of bovine leukemia virus by using an enzyme-linked assay for polymerase chain reaction-amplified proviral DNA in experimentally infected cattle. AB - Bovine leukemia virus is the causative agent of bovine leukosis and has been described in many countries throughout the world. We describe here a sensitive and readily applicable assay for the detection of bovine leukemia proviral DNA. Detection relies on initial amplification of proviral DNA by using polymerase chain reaction (PCR) followed by an enzyme-linked assay (PCR-ELA). Amplification is carried out by using one biotinylated primer and a second primer containing the GCN4 protein binding site. DNA is detected by a colorimetric assay after it is coupled to GCN4-coated plates and subsequently incubated with horseradish streptavidin peroxidase and the appropriate substrate to produce a chromogenic reaction. It was possible to detect proviral DNA for all of eight bovine leukemia virus-infected calves by 2 weeks postinfection. Use of the more conventional agar gel immunodiffusion assay failed to reveal the presence of the virus in any of the animals up to 4 weeks postinfection. The PCR-ELA detected as little as 0.1 to 0.2 ng of amplified DNA per well, which compares very favorably with ethidium bromide staining of gels, by which 1 to 2 ng per lane was detected. This method lends itself to mass screening, is carried out in a similar way to an enzyme linked immunosorbent assay, and does not require gel electrophoresis or the use of radioactive gene probes. PMID- 1313048 TI - Detection of cytomegalovirus in urine samples by an enzyme-linked immunosorbent assay using a monoclonal antibody against the viral 150-kilodalton protein. AB - McKeating et al. (J.A. McKeating, P.D. Griffiths, and J.E. Grundy, J. Gen. Virol. 68:785-792, 1987; J. A. McKeating, J. E. Grundy, Z. Varghese, and P. D. Griffiths, J. Med. Virol. 18:341-348, 1986; J. A. McKeating, S. Stagno, P. R. Stirk, and P. D. Griffiths, J. Med. Virol. 16:367-373, 1985) reported previously that beta 2 microglobulin inhibits the detection of human cytomegalovirus (CMV) in urine specimens by an enzyme-linked immunosorbent assay (ELISA) with a monoclonal antibody against the glycoprotein of CMV. They postulated that beta 2 microglobulin binds to the viral glycoproteins and masks the antigenic determinants. We developed here an ELISA method for the detection of CMV in urine by using a monoclonal antibody against the viral 150-kDa protein to capture the viral antigen. This assay detected CMV both in culture medium and in urine specifically at concentrations higher than 10(3) PFU/ml and quantitatively at concentrations higher than 10(4) PFU/ml. The sensitivity of the ELISA increased about 10-fold when peroxidase-labeled F(ab')2 from goat anti-human immunoglobulin G was used as a secondary detecting antibody in combination with concentration of the virus in urine samples by ultracentrifugation. The inhibition of ELISA by beta 2 microglobulin was not observed in this ELISA system. When 56 urine specimens from renal transplant recipients were examined for CMV antigens, the ELISA system had a sensitivity of 78% and a specificity of 97%. The positive and negative predictive values of the assay were 95 and 86%, respectively. Furthermore, CMV antigens in urine were quantitated by the assay during the course of typical CMV disease of renal transplant recipient. These results suggest strongly that the measurement of CMV antigens in urine by our rapid and quantitative ELISA system provides very useful data for the monitoring of CMV infections in renal transplant recipients and making decisions about therapy. PMID- 1313049 TI - Epidemiology of Yersinia pseudotuberculosis and Y. enterocolitica infections in sheep in Australia. AB - Infections with Yersinia pseudotuberculosis serotype III and Y. enterocolitica serotype O2,3 were found to be common in Australian sheep flocks. Transmission of Y. pseudotuberculosis occurred in late winter and early spring, while Y. enterocolitica transmission occurred from midwinter to early summer. Excretion of Y. pseudotuberculosis was limited to the winter and spring period and was particularly common in 1- and 2-year-old sheep. Infection persisted for up to 14 weeks. Y. pseudotuberculosis infection did not confer immunity to natural infection with Y. enterocolitica. Y. enterocolitica excretion occurred year round, with the greatest prevalence being in summer and autumn. Infection persisted for up to 29 weeks. Sheep less than 1 year old were most commonly infected with Y. enterocolitica. Infection with either Y. pseudotuberculosis or Y. enterocolitica was rare in aged sheep. Restriction endonuclease analysis of Y. pseudotuberculosis serotype III from sheep, cattle, deer, and pigs showed that the bacterial isolates were genetically indistinguishable. Similarly, Y. enterocolitica isolates from sheep were indistinguishable from those isolated from goats and cattle. PMID- 1313050 TI - Evaluation of a microtiter plate fluorescent-antibody assay for rapid detection of human cytomegalovirus infection. AB - The use of monoclonal antibody (MAb) p63-27, which is reactive with the major immediate-early human cytomegalovirus (HCMV) protein pp72, was explored for the rapid diagnosis of HCMV viruria. The rapid assay detected all but 1 of 19 specimens identified by standard virus isolation methods from 1,676 newborn urine specimens, achieving a sensitivity of 94.5% and a specificity of 100%. The monoclonal antibody recognized 260 randomly obtained clinical isolates of HCMV, indicating the suitability of this reagent for use in screening assays. The sensitivity of the microtiter plate method declined rapidly for specimen from older infants and children with congenital CMV infection and virus-infected children attending a day-care center and was judged to be unacceptable for screening populations in this age group. PMID- 1313051 TI - Use of polymerase chain reaction-amplified Helicobacter pylori urease structural genes for differentiation of isolates. AB - Helicobacter pylori has been demonstrated as an etiologic agent of human gastritis and peptic ulcer formation. However, there is no straightforward basis to distinguish different isolates. We used the polymerase chain reaction (PCR) to amplify the urease structural subunit genes, ureA and ureB, which, when digested with appropriate restriction endonucleases, allow the differentiation of patterns on agarose gels. PCR amplification was possible with DNA rapidly extracted from H. pylori by alkaline lysis and phenol-chloroform. The 2.4-kb PCR products amplified from 22 clinical isolates and subjected to HaeII restriction endonuclease digestion produced 10 distinct patterns on agarose gels, with two patterns being shared between five and six strains. PCR amplification of the urease genes may enable the differentiation of closely related H. pylori strains by restriction digest analysis of PCR-amplified ureA and ureB genes. PMID- 1313052 TI - Disk diffusion quality control guidelines for Haemophilus susceptibility tests using cefdinir, CI-960, fleroxacin, temafloxacin, and trospectomycin. AB - A multilaboratory study to determine disk diffusion quality control ranges for Haemophilus influenzae ATCC 49247 and five investigational drugs was performed. Multiple lots of Haemophilus Test Medium and antibiotic disks were used for replicate testing in conformance with the recommendations of the National Committee for Clinical Laboratory Standards. Quality control disk zone diameter ranges were proposed for cefdinir, CI-960, fleroxacin, temafloxacin, and trospectomycin. PMID- 1313053 TI - Effects of anticoagulants and storage of blood samples on efficacy of the polymerase chain reaction assay for hepatitis C virus. AB - Blood samples from 11 patients with posttransfusion hepatitis C virus infection were collected. Each sample was divided into three fractions to obtain sera, sodium-citrated plasma, and heparinized plasma and then tested for HCV RNA by a nested polymerase chain reaction (PCR). Of them, eight sodium-citrated plasma samples, seven serum samples, and no heparinized plasma samples were PCR positive. Eight PCR-positive sodium-citrated plasma samples were exposed to different physical conditions and semiquantified for HCV RNA after serial dilutions. Samples stored at -70 degrees C showed the best preservation of HCV RNA, and storage at the other conditions resulted in only minimal loss of the PCR signal. Therefore, serum or sodium-citrated plasma specimens are satisfactory for detecting HCV RNA by PCR, but heparinized blood specimens are not. PMID- 1313054 TI - Syndrome of inappropriate antidiuretic hormone secretion. PMID- 1313055 TI - Epithelioid cell histiocytoma. A clinicopathologic and immunohistochemical study of eight cases. AB - BACKGROUND: Epithelioid cell histiocytomas histologically resemble the intradermal form of Spitz nevus. OBJECTIVE: We have studied eight patients with epithelioid cell histiocytoma. METHODS: In addition to the routine stains, histologic sections were prepared by immunohistochemical techniques for S-100 protein, HMB-45, vimentin, alpha 1-antitrypsin, and common leukocyte antigen. RESULTS: Epithelioid cell histiocytoma is characterized by proliferation of angulated epithelioid cells with abundant eosinophilic cytoplasm. Immunostaining for S-100 protein and HMB-45 were negative. The majority of cells had positive reactions to staining for vimentin and alpha 1-antitrypsin. Approximately 20% to 25% of cells also gave positive reactions to common leukocyte antigen. CONCLUSION: Immunostainings are useful in the differential diagnosis of epithelioid cell histiocytoma from the intradermal form of Spitz nevus. PMID- 1313056 TI - Comparison of the nutrient intakes of blacks, Siouan Indians, and whites in Columbus County, North Carolina. PMID- 1313057 TI - GABA and epilepsy: their complex relationship and the evolution of our understanding. AB - Because of its abundance in the brain, its ability to produce hyperpolarizing inhibition of almost all neurons, its association with benzodiazepines, and the discovery that many convulsants inhibited its synthesis, gamma-aminobutyric acid (GABA) has often appeared to be the key to epilepsy. Many assumed that "primary" or "genetic" epilepsy must be a disorder of GABA synapses and that GABA agonists would be universal anticonvulsants if permeability and drug metabolism were controlled. The GABA synthetic gene was a logical "candidate gene" for epilepsy. However, the GABA-deficiency theory of epilepsy is less convincing today. GABA agonists were found to intensify seizures in some rodent and human cases. Absence and other generalized seizures in humans often worsened when treated with GABA transaminase inhibitors such as gamma-vinyl-GABA. Surprisingly, the GABA transaminase inhibitors appear to be more useful in partial than in generalized epilepsies. Neuronal GABA uptake blockers are proconvulsant. GABA agonists aggravate seizures in several mutants, ranging from the photosensitive baboon to the genetically epilepsy-prone rat. How can this be understood? Muscimol injections into the pedunculopontine nucleus increase seizures due to systematically administered convulsants, while the receptor blocker bicuculline suppresses seizures after injection into several brain regions, including the striatum. The result of inhibiting inhibitory circuits is excitation. Studies with GABA uptake blockers and the GABAB agonist baclofen are presented in which their combined administration provoked seizures in rats. Baclofen was shown also to increase the incidence of seizures evoked by pentylenetetrazole without increasing seizures due to local injections of excitatory amino acids. Baclofen antagonized the myoclonic effect of 5-hydroxytryptophan in rats with serotonin lesions. Baclofen augments some seizures and inhibits others. Selective inhibition of a particular tract, whether GABAergic or not, may have convulsant or anticonvulsant effects, depending on its connections and the state of the organism. GABAA receptor stimulation is usually but not always anticonvulsant. GABAB receptor stimulation may facilitate absence seizures and related primary generalized seizures. GABAB receptors may be abnormal in some forms of nonfocal epilepsy seen in childhood. It is likely that mutations of GABA transporter and GABAA receptor genes will be found in humans but they will probably not be patients with "pure epilepsy." PMID- 1313058 TI - A neurologist's approach to neuroblastoma. AB - Neuroblastoma is among the most common malignancies of childhood. Despite greatly improved therapy for some pediatric tumors, the prognosis for children with metastatic neuroblastoma has not changed significantly in the past 10 years. With conventional chemotherapy, radiation therapy, and surgery, children with metastatic neuroblastoma have a 20% long-term survival rate. We have pursued novel chemotherapeutic approaches to neuroblastoma that target the neurotransmitter receptors on the surface of these cells. Specificity for these neural crest tumor cells is effected by (1) selective protection of normal neuronal elements from toxicity, or (2) selective potentiation of toxicity for neural tumor cells. In the first instance, the oxygen radical-generating neurotransmitter analogue 6-hydroxydopamine is used as a neural crest-specific toxin. Normal neural crest cells are protected from this toxicity by oxygen radical-scavenging analogues of the compound WR2721, which is specifically taken up by nonneoplastic cells. In the second instance, neocarzinostatin, an antineoplastic natural product that must be activated by thiol groups to be toxic, is used in conjunction with 6-mercaptodopamine, a thiol-containing compound that gains specific entry into neural crest cells by virtue of its neurotransmitter-like structure. We have found that neocarzinostatin induces morphologic differentiation of neuroblastoma cells, and we are also currently characterizing the biochemical accompaniments of this morphologic change. PMID- 1313059 TI - Creatine kinase in epithelium of the inner ear. AB - Epithelium of the inner ear in the gerbil and mouse was examined immunocytochemically for presence of creatine kinase (CK). Marginal cells of the cochlear stria vascularis and dark cells and transitional cells of the vestibular system were found to contain an abundance of the MM isozyme (MM-CK). CK in these cells concurs with that which is coupled to Na,K-ATPase in other cells and is considered to supply ATP for the Na,K-ATPase that mediates the high KCl of endolymph. Inner hair cells revealed content of the BB isozyme and in this respect resembled the energy-transducing photoreceptor cells in retina. In addition, outer phalangeal (Deiters') cells stained for both MM- and BB-CK whereas inner phalangeal cells evidenced content of only the BB isozyme. Immunolocalization of CK appeared similar in mouse and gerbil inner ear. Specificity of the staining was affirmed by observations in agreement with those reported for CK in various cell types and by staining with antisera from more than one source. PMID- 1313060 TI - Distribution of 3-hydroxybutyrate dehydrogenase in primary lobules of rat liver. AB - In an attempt to establish the functional organization of the hepatic parenchymal unit, we used histo- and microchemical procedures to assess metabolic liver cell heterogeneity at the level of the primary lobule. Because of the close interrelation of glucogenesis and ketone body formation, and in view of the distinct regional differences of the in vivo activity of glucose-6-phosphatase (G6Pase), these techniques were used on livers from male rats to investigate the distribution of the ketogenic enzyme, 3-hydroxybutyrate dehydrogenase (3-HBDH), during the post-resorptive phase. A close reciprocity was found between the general increase in the activity of 3-HBDH and the decrease of the in vivo activity of G6Pase along the sinusoidal axis, and also with regard to enzyme gradients along sinusoids of different origin. The activity of the ketogenic enzyme was higher throughout septal than portal sinusoids, whereas the opposite applied to the glucogenic enzyme. Histo- and microchemical data support the concept of a lobular parenchymal unit composed of "primary lobules," and show also that hepatocyte function varies with cell location along the sinusoidal axis and with the origin of the sinusoids. PMID- 1313061 TI - Intracellular amplification of proviral DNA in tissue sections using the polymerase chain reaction. AB - We developed a new method to amplify cell DNA in situ using the polymerase chain reaction (PCR). Proviral sequences of mouse mammary tumor virus (MMTV) contained in cultured cells and tissue sections were amplified intracellularly using a thermal cycler. Two techniques were employed to maintain the localization of the amplified DNA. First, complementary tails at the 5' ends of the oligonucleotide primers resulted in the synthesis of high molecular weight concatamers containing the target sequences. Second, the PCR was carried out in a thin film of agarose solidified over the tissue sections. The specifically amplified and localized DNA was then detected by in situ hybridization (ISH). Our results demonstrate that (a) DNA in tissue sections can serve as the target for the polymerase chain reaction in situ, (b) cell morphology is maintained, and (c) a target of 167 BP can be specifically detected in individual cells. This technique should be generally applicable to amplifying cellular DNA targets in tissue sections for detection in situ. PMID- 1313062 TI - Double in situ hybridization for detection of Herpes simplex virus and cytomegalovirus DNA using non-radioactive probes. AB - We describe a double in situ hybridization assay for the simultaneous detection of Herpes simplex virus (HSV) and cytomegalovirus (CMV) DNA in infected cell cultures using non-radioactive-labeled probes. This work used a biotinylated HSV DNA probe, which can be revealed by an avidin-biotin-peroxidase complex and a digoxigenin-labeled CMV DNA probe, visualized by anti-digoxigenin F(ab) fragments conjugated with alkaline phosphatase. Light microscopy visualization was achieved by the contrasting colors of appropriate peroxidase and alkaline phosphatase reaction products (red and dark blue, respectively). The time required to perform the double hybridization assay was about 3 hr. This double hybridization assay proved to be sensitive, specific, and provided good resolving power. PMID- 1313063 TI - Simultaneous assessment of TGFB and cell cycle kinetics using IUdR/BrdU infusions in human neoplasms from plastic-embedded tissue. AB - We describe an immunohistochemical technique that makes use of two monoclonal antibodies (MAb), one to detect the transforming growth factor B (TGFB) and another that reacts with iodo- and bromodeoxyuridine. The purpose of this technique is to determine the relationship between TGFB expression and the S phase cells in human tumors. Since both can be distinctly identified in situ from tissue embedded in plastic, in assessment of the geographic orientation of S phase cells in relation to such factors as TGFB, contiguity to blood vessels, nerve fibers, and macrophages can also be achieved. PMID- 1313064 TI - Differential expression of the alpha 2 and beta messenger RNAs of Na,K-ATPase in developing brine shrimp as measured by in situ hybridization. AB - We used in situ hybridization histochemistry with synthetic oligonucleotide probes to localize the mRNAs encoding the alpha 2- and beta-mRNAs of Na,K-ATPase during development of the brine shrimp Artemia. The mRNAs of the alpha 2- and beta-subunit were of low abundance in the cysts; in addition, less mRNA of the beta-subunit was localized. During emergence (12 hr), there was an increase in alpha 2-subunit mRNA in the gut mucosa, but there was a burst in beta-subunit mRNA throughout. As development progressed, the mRNAs of both the alpha 2- and beta-subunits showed a distinct pattern of expression in which the mRNA in the salt gland was of greatest abundance, followed by epidermal cells and gut mucosa. After 36 hr the alpha 2-subunit mRNA began to decrease in all positive cells but still remained highest in the salt gland and the brain region, while the mRNA of the beta-subunit kept increasing in the gut mucosa. Finally, the greatest abundance of the beta-subunit mRNA shifted from the salt gland to the antenna gland and the epidermal cells in the tail region, but the alpha 2-subunit mRNA did not. The more widespread distribution of the beta-mRNA than alpha 2-mRNA at certain stages (e.g., there was no alpha 2-mRNA in the antenna gland at the adult stage) is in all likelihood due to the marked drop in the alpha 2-subunit and a rise in alpha 1-subunit previously seen by Peterson et al. on polyacrylamide gel electrophoresis, as development progresses. PMID- 1313065 TI - Retrograde tracing of zinc-containing neurons by selenide ions: a survey of seven selenium compounds. AB - The autometallographic retrograde tracing of zinc-containing neurons by intracerebral injection of sodium selenite (Na2SeO3), introduced by Danscher in 1982, has recently been described in more detail. Intracerebral injections of both sodium selenide (Na2Se) and sodium selenite (Na2SeO3) have been successfully used; however, sodium selenite had a rather toxic effect on the injected tissue. In the present study, we tested seven different selenium compounds to find the most suitable compound for retrograde tracing of zinc-positive pathways. Among the tested compounds, sodium selenide (Na2Se) caused insignificant necrosis within the injection site and was easily transported retrogradely when handled anaerobically. Sodium selenide is therefore recommended as the compound of choice. PMID- 1313066 TI - Peripheral blood mononuclear cells of the elderly contain varicella-zoster virus DNA. AB - Peripheral blood mononuclear cells (PBMC) from humans of different ages were analyzed for DNA sequences specific for varicella-zoster virus (VZV) genes 29 and 62 by polymerase chain reaction (PCR). Neither VZV gene was detected in DNA from umbilical cord blood PBMC of 10 infants or from blood PBMC of two 3-year-old children. In 22 humans less than 60 years old, gene 29 was not detected, and gene 62 was detected in only one subject. In 33 humans greater than 60 years old, including patients with postherpetic neuralgia, PBMC from 4 subjects contained gene 29, 4 contained gene 62, and 1 contained both genes. The presence of VZV DNA correlated significantly with age (P less than .05, chi 2 and logistic regression analysis), but not with gender or postherpetic neuralgia. PMID- 1313067 TI - Prevention of human rotavirus-induced diarrhea in gnotobiotic piglets using bovine antibody. AB - The efficacy of passively administered bovine antibody for preventing human rotavirus (HRV)-induced diarrhea was investigated using a gnotobiotic pig model. Cows were immunized with inactivated HRV serotypes 1 (Wa) and 2 (S2) and simian rotavirus serotype 3 (SA11), and immune colostrum and milk were collected. Antibody concentrates derived from these materials were fed to germ-free piglets that were subsequently inoculated with HRV Wa. Both viral shedding and diarrhea were effectively reduced or eliminated in a dose-dependent manner as a result of HRV immune antibody feeding. A quantitative virus-neutralizing (VN) antibody method permitted assessment of the functional antibody dose required to achieve a 50% reduction of disease (PD50). PD50 dose levels of 15.8 and 19.5 x 10(6) VN antibody units were determined for inhibition of diarrhea and viral shedding, respectively. Studies reported here provide new information on the quantitative relationship between protective antibody dose and diarrheal disease response. PMID- 1313068 TI - Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus. AB - Death due to Japanese encephalitis usually occurs in the first 5 days of hospitalization as a result of deepening coma with respiratory arrest. Death may result from edema-induced increases in intracranial pressure that might be reduced by the administration of steroids. Sixty-five patients presenting in Thailand to four hospitals with a diagnosis of acute Japanese encephalitis were randomized in a double-masked fashion and stratified by initial mental status into a placebo group (saline) or a treatment group (dexamethasone 0.6 mg/kg intravenously as a loading dose followed by 0.2 mg/kg every 6 h for 5 days). Fifty-five of the 65 had confirmed Japanese encephalitis as demonstrated by detection of virus or by Japanese encephalitis virus-specific IgM antibody. Important outcome measures included mortality (24%, treatment group; 27%, control group), days to alert mental status (3.9 vs. 6.2), and neurologic status 3 months after discharge (45% abnormal in each group). No statistically significant benefit of high-dose dexamethasone could be detected. PMID- 1313069 TI - High-level quinolone resistance in clinical isolates of Campylobacter jejuni. AB - During a recent clinical trial of ciprofloxacin in the therapy of acute diarrhea, two subjects infected with Campylobacter jejuni who received ciprofloxacin failed microbiologically and one also failed clinically. Although both pretreatment isolates were susceptible to ciprofloxacin, the posttreatment isolates were resistant to ciprofloxacin (MIC = 32 micrograms/ml) and to other quinolones. The posttreatment isolates remained susceptible to nonquinolone antimicrobials. DNA gyrase holoenzyme was isolated from one of the resistant posttreatment isolates and was 8- to 16-fold less sensitive to inhibition by ciprofloxacin than was the gyrase from the paired pretreatment susceptible isolate. Ciprofloxacin accumulation was diminished in the two resistant posttreatment isolates. These results show that mutation in C. jejuni can occur in vivo and is associated with clinically significant resistance to the newer quinolones. PMID- 1313070 TI - Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction. AB - Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates. PMID- 1313071 TI - Oral bioavailability and anti-simian varicella virus efficacy of 1-beta-D arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) in monkeys. AB - BV-araU (1-beta-D-arabinofuranosyl-E-5-[2-bromovinyl]uracil) has potent antiviral activity against varicella zoster virus in cell culture and is undergoing clinical evaluation. In the present study, pharmacokinetic parameters and the efficacy of BV-araU against infection with simian varicella virus (SVV) were evaluated in African green monkeys. Pharmacokinetic parameters were determined by analysis of the BV-araU content of sera obtained after oral and intravenous administration to normal monkeys. Peak serum concentrations showed dose proportionality, with the 0.1 mg/kg dose resulting in a peak serum concentration of 0.05 micrograms/ml, the approximately ED50 value for the SVV inoculum in cell culture. BV-araU administered orally twice daily at 0.1 mg/kg for 10 days starting 48 h after intratracheal SVV infection prevented vesicular rash development and suppressed viremia. Effective therapy could be initiated 96 h after infection. Taken together, these results indicate that BV-araU is effective oral therapy at doses that achieve peak serum levels equivalent to the ED50 for SVV in cell culture. PMID- 1313072 TI - A phorbol diester resistant monocytic leukemia cell line is PKC deficient. AB - MIA C51 is a rat monocytic leukemia cell line which exhibits undifferentiated monocytic phenotype in culture. The proliferation of MIA C51 cells was not inhibited by the addition of 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 1 microgram/ml) or phorbol 12, 13 dibutyrate (PDBu, 10 micrograms/ml). Comparison of MIA C51 cells to a phorbol diester-sensitive human monoblastoid U-937 cell line demonstrated that MIA C51 cells contained significantly lower number of PDBu receptors, protein kinase C (PKC) activity, and PKC protein level. Further experiments demonstrated that addition of TPA to MIA C51 cells did not induce the expression of c-fos proto-oncogene; whereas incubation of MIA C51 cells with N6, O2-dibutyryl cyclic adenosine 3',5' monophosphate (Bt2cAMP) resulted in a rapid increase of c-fos mRNA level. Thus, this cell line provides a new system for studying the signal transduction mechanisms in induced monocytic differentiation. PMID- 1313073 TI - Regulation of guinea pig plasma low density lipoprotein kinetics by dietary fat saturation. AB - Dietary fat saturation has been shown to affect hepatic apoB/E receptor expression and to modify low density lipoprotein (LDL) composition and density in guinea pigs. The current studies were designed to investigate the independent and interactive effects of dietary fat saturation alterations in apoB/E receptor expression and LDL composition on in vivo LDL turnover kinetics, both receptor mediated and receptor-independent. Guinea pigs were fed semi-purified diets containing 15% fat, either polyunsaturated corn oil (CO), monounsaturated olive oil (OL), or saturated lard, and injected with radioiodinated LDL isolated from animals fed the homologous diet. Blood samples were obtained over 33 h to determine apoLDL fractional catabolic rates (FCR) and flux rates. Compared to animals fed OL- or lard-based diets, intake of the CO-based diet resulted in a 50% decrease in LDL apoB pool size associated with a twofold increase in receptor mediated FCR (P less than 0.001) and a 28% decrease in flux rate (P less than 0.05). Maximal LDL binding capacity of hepatic apoB/E receptors, determined in vitro, was twofold higher for animals fed the CO-based diet compared to guinea pigs fed the OL- and lard-based diets (P less than 0.01). There was a significant correlation between hepatic apoB/E receptor number and in vivo receptor-mediated LDL FCR (r = 0.987). Significant differences in LDL turnover were related to the source of LDL. When injected into animals fed a nonpurified commercial diet, the smaller, cholesteryl ester-depleted LDL isolated from animals fed the CO-based diet had a twofold higher FCR compared to larger LDLs from guinea pigs fed the OL and lard-based diets, which had similar turnover rates. When LDL from animals fed the commercial diet was radiolabeled and injected into animals fed the three types of dietary fat, significant differences in LDL turnover were observed in the order CO greater than lard greater than OL, suggesting that intravascular processing and tissue uptake of the smaller LDL from animals fed the commercial diet varies depending on the dietary fat saturation fed to the recipient animals. These studies demonstrate that guinea pigs fed polyunsaturated fat diets lower plasma LDL levels in part by an increase in apoB/E receptor-mediated fractional LDL turnover and a decrease in apoLDL flux. In addition, fat saturation alters LDL composition and size which independently affect LDL turnover rates in vivo. PMID- 1313074 TI - The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor. AB - Insulin-like growth factor I (IGF-I)/somatomedin C is an important mediator of keratinocyte growth in vitro, and the expression of IGF-I receptors in the basal layer of normal epidermis suggests that this growth pathway may function in the regulation of keratinocyte growth in vivo as well. The pattern of IGF-I receptor expression in normal skin is distinct from that of the epidermal growth factor (EGF) receptor, suggesting that these receptors might be differentially regulated. The purpose of this study was to obtain a better understanding of IGF I receptor function in the skin by examining IGF-I receptor expression in psoriatic epidermis and in cultured human keratinocytes. Our findings indicate that IGF-I receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF-I receptor-specific monoclonal antibody. Unlike EGF receptor expression, which is also increased in psoriatic epidermis, the pattern of IGF-I receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis. Biochemical agents that diminish EGF receptor ligand binding (phorbol ester or calcium ionophore treatment) produce opposite effects on the IGF-I receptor. These results suggest that cellular expression and differential regulation of both growth factor receptor systems may control critical aspects of epidermal proliferation or function. PMID- 1313075 TI - CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation. AB - Activation of an immune response requires intercellular contact between T lymphocytes and antigen-presenting cells (APC). Interaction of the T cell antigen receptor (TCR) with antigen in the context of major histocompatibility molecules mediates signal transduction, but T cell activation appears to require the induction of a second costimulatory signal transduction pathway. Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal. To investigate the role of CD28 signal transduction during APC-dependent T cell activation, we have used Staphylococcal enterotoxins (SEs) presented by a B7-positive APC. We used anti-B7 monoclonal antibodies and a mutant interleukin 2 (IL-2) promoter construct, unresponsive to CD28-generated signals, in transient transfection assays to examine the contribution of the CD28 B7 interaction to IL-2 gene activation. These studies indicate that the CD28 regulated signal transduction pathway is activated during SE stimulation of T cells and plays an important role in SE induction of IL-2 gene expression through its influence upon the CD28-responsive element contained within the IL-2 gene promoter. This effect is particularly profound in the activation of the IL-2 gene in peripheral blood T cells. PMID- 1313076 TI - Adult adrenoleukodystrophy: the clinical spectrum in a large Dutch family. AB - A large family with adrenoleukodystrophy is described and the case histories of two clinically symptomatic and related male patients are presented. Clinical, biochemical and genetic screening of their family demonstrated two clinically affected males, one biochemically affected male and five carrier females. Two women were symptomatic; one suffered an acute exacerbation. One female was diagnosed as a carrier, based on genetic analysis and the family history only. Endocrinological screening was performed in the five affected males, demonstrating an elevated adrenocorticotrophic hormone level and a normal cortisol level in two, as evidence of compensated adrenocortical failure. PMID- 1313077 TI - Detection of varicella-zoster virus DNA by polymerase chain reaction in cerebrospinal fluid of patients with herpes zoster meningitis. AB - In three of five patients with herpes zoster meningitis, varicella-zoster virus (VZV) DNA was detected by the polymerase chain reaction (PCR) in the initial samples of cerebrospinal fluid. DNA fragments of group A or B, following classification of VZV strains by the size of the variable region IV of VZV genome, were found at the 7th, 10th and 24th illness day in the three positive cases: one of these cases did not have skin lesions. These results suggest that the detection of VZV DNA by PCR is useful for the diagnosis of herpes zoster meningitis, as well as for its molecular epidemiology. PMID- 1313079 TI - Multifocal peripheral neuropathy in eosinophilic fasciitis. AB - Polyneuropathy may complicate eosinophilia-associated connective tissue disease. We report a multi-focal neuropathy in a patient with eosinophilic fasciitis proven by demonstrating an eosinophilic cellular infiltrate in a fascial biopsy specimen from the forearm. Sural nerve biopsy revealed lymphocytic cuffing of epineural arterioles. Although described in the L-tryptophan-related eosinophilia myalgia syndrome, peripheral neuropathy with these features has not been previously noted in a patient with eosinophilic fasciitis who had not consumed L tryptophan. PMID- 1313078 TI - A double-blind placebo-controlled trial of L-threonine in amyotrophic lateral sclerosis. AB - Fifteen patients with the unequivocal diagnosis of amyotrophic lateral sclerosis (ALS) completed a 1-year randomized double-blind placebo-controlled trial of L threonine (2 g daily). During the study, patients in the placebo group showed a decline in functional status consistent with the natural history of ALS, which was not statistically different from outcome in the patients in the L-threonine group. PMID- 1313080 TI - Calcium-dependent potassium currents in neurons from cat sensorimotor cortex. AB - 1. Ca(2+)-dependent K+ currents were studied in large pyramidal neurons (Betz cells) from layer V of cat sensorimotor cortex by use of an in vitro brain slice and single microelectrode voltage clamp. The Ca(2+)-dependent outward current was taken as the difference current obtained before and after blockade of Ca2+ influx. During step depolarizations in the presence of tetrodotoxin (TTX), this current exhibited a fast onset of variable amplitude and a prominent slowly developing component. 2. The Ca(2+)-dependent outward current first appeared when membrane potential was stepped positive to -40 mV. Downsteps from a holding potential of -40 mV revealed little or no time-, voltage-, or Ca(2+)-dependent current. When membrane potential was stepped positive to -40 mV, a prolonged Ca(2+)-dependent outward tail current followed repolarization. The decay of this tail current at -40 mV was best described by a single exponential function having a time constant of 275 +/- 75 (SD) ms. The tail current reversed at 96 +/- 5 mV in 3 mM extracellular K+ concentration ([K+]o) and at more positive potentials when [K+]o was raised, suggesting that it was carried predominantly by K+. 3. The Ca(2+)-dependent K+ current consisted of two pharmacologically separable components. The slowly developing current was insensitive to 1 mM tetraethylammonium (TEA), but a substantial portion was reduced by 100 nM apamin. Most of the remaining current was blocked by the addition of isoproterenol (20-50 microM) or muscarine (10-20 microM). 4. The time courses of the apamin- and transmitter-sensitive components were similar when activated by step depolarizations in voltage clamp, but they were quite different when activated by a train of action potentials. Applying the voltage clamp at the end of a train of 90 spikes (evoked at 100-200 Hz) resulted in an Ca(2+)-dependent K+ current with a prominent rapidly decaying portion (time constant approximately 50 ms at -64 mV) and a smaller slowly decaying portion (time constant approximately 500 ms at 64 mV). The rapidly decaying portion was blocked by apamin (50-200 nM), and the slowly decaying portion was blocked by isoproterenol (20-50 microM). 5. When recorded with microelectrodes containing 2 mM dimethyl-bis-(o-aminophenoxy) N,N,N',N'-tetraacetic acid (dimethyl-BAPTA), which causes prolonged afterhyperpolarizations, the Ca(2+)-dependent K+ current evoked by step depolarizations had an extremely slow onset and decay. The current recorded after a train of evoked spikes had a similar slow decay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1313081 TI - Tertiary and quaternary local anesthetics protect CNS white matter from anoxic injury at concentrations that do not block excitability. AB - 1. Anoxic injury in CNS white matter was studied using the in vitro rat optic nerve preparation. Optic nerves were subjected to 60 min of anoxia, and functional recovery was assessed using the area under the compound action potential (CAP). In normal cerebrospinal fluid, CAP area recovered to 33.5 +/- 9.3% (SD) of control. 2. Lidocaine and procaine (0.1 or 1.0 mM), applied beginning 1 h before anoxia, significantly improved postanoxic recovery of CAP area. However, both agents also depressed the preanoxic CAP. Procaine generally allowed greater recovery with less depression compared with lidocaine. 3. The quaternary derivatives QX-314 (0.1-1.0 mM) and QX-222 (0.3-3.0 mM) resulted in more complete recovery of the CAP area from anoxia, with less depression of preanoxic excitability, compared with the tertiary compounds. At 0.3 mM, QX-314 reduced the preanoxic CAP very little (to 94.4 +/- 14% of control CAP area), yet allowed the postanoxic CAP area to recover to 99.6 +/- 19%. 4. We conclude that quaternary local anesthetics are more effective at protecting CNS white matter tracts from anoxia than tertiary compounds and that these agents can result in markedly improved recovery even at concentrations that do not block conduction. Moreover, given the relative specificity of QX-314 for noninactivating Na+ channels, we hypothesize that this channel subtype plays an important role in mediating anoxic injury in central myelinated axons. PMID- 1313082 TI - High myocardial accumulation of radioiodinated digoxin derivative: a possible Na,K-ATPase imaging agent. AB - In view of the high binding ability of cardiac glycosides to the myocardial Na,K ATPase, radioiodinated digoxin derivatives were surveyed as candidates for myocardial imaging, with particular emphasis on the noninvasive monitoring of cardiac glycoside therapy. Among the radioiodinated digoxin derivatives surveyed, 125I-digoxin-iodohistamine(bis(O-carboxymethyloxime)) showed the highest accumulation in the myocardium and similar binding ability to Na,K-ATPase as digoxin itself against ouabain displacement, as indicated by in vivo and in vitro studies. Based on these results, 123I labeling of digoxin-histamine(bis(O carboxymethyloxime)) and imaging in a dog demonstrated uptake in the myocardium. PMID- 1313083 TI - Effects of structured controversy on students' perceptions of their skills in discussing controversial issues. AB - The teaching strategy that educators use when addressing controversial issues can help students develop the skills they need to deal effectively with controversial issues. Structured controversy is designed to allow students to practice these skills. This study measured the change in students' perceptions of their skills in perspective-taking, logical arguing, and reaching consensus after using structured controversy on two controversial issues. Results of two-factor analyses of variance and comparison of means indicate significant positive changes in 51 senior nursing students' perceptions of their skills in perspective taking (less than .001), logical arguing (less than .01), and reaching consensus (less than .01). These results are consistent with findings of previous research studies on the effectiveness of structured controversy. PMID- 1313084 TI - Participation of nursing faculty in university governance. AB - It has been suggested that faculty participation in governance in American colleges is low, and that faculty in schools of nursing are particularly unlikely to be involved in governance activities. This study was designed to determine actual and ideal levels of nursing faculty participation in five areas of governance: academic, student, personnel, public, and financial affairs. A survey of nursing faculty suggested that they were involved substantially in academic affairs, but less involved in the other areas of governance. Generally, the faculty indicated satisfaction with their high level of participation in academic affairs, and with their lower level of participation in student affairs, personnel affairs, and public affairs; the faculty did indicate dissatisfaction with their low level of participation in financial affairs. PMID- 1313085 TI - Power and change in health care: challenge for nursing. AB - This article proposes the need for consideration of status and power issues in nursing research, in theory, and at all levels of nursing education. Including the concept of power in nursing curricula will better prepare nurses to participate in social and political decisions affecting health care. By recognizing the role nurses have played, often in the face of opposition, nursing students will gain a sense of the potential power and strength of nurses. Curricular reform and revision of nursing theories to emphasize the sociopolitical context of nursing may change the socialization of student nurses by stressing autonomy, independence, and confidence. These changes may have a positive impact on recruitment, retention, and on efforts to change the public's perception of nursing. PMID- 1313086 TI - Empowerment through teaching. AB - Empowerment through teaching is built on the feminist belief that successful and effective teaching is a cointentional process, emerging from meaningful connections between students and faculty. Empowerment results from teaching characterized by caring, commitment, creativity, interaction, and a recognition of the humanity of both teacher and students. Teaching is conceptualized as a directional process emerging from the energy of both student and teacher. There must be continued, intense, and frequent exchange of these energies. The tools that students and teacher must possess or acquire for empowerment include positive self-concept, creativity, resources, information, and support. This perspective permits a new understanding of teaching that results in empowerment of both parties involved in the process of learning. PMID- 1313087 TI - The professional self-concepts of nursing undergraduates and their perceptions of influential forces. AB - This article explores the professional self-concepts of senior nursing undergraduates and their perceptions of the most significant forces that influenced the process. The method was qualitative; a grounded theory approach was used. The sample included 23 senior baccalaureate nursing students in their final clinical rotation prior to graduation. Audiotaped interviews were analyzed through the constant comparative method. Informants overwhelmingly perceived themselves as caring. They valued professional competence and many identified a lack of confidence in their skills. Caring qualities, caring role models, and qualities of the role models are listed. PMID- 1313088 TI - Knowledge about aging and Alzheimer's disease among baccalaureate nursing students. AB - Alzheimer's disease (AD) is a debilitating disease that poses many physical, social, psychological, and management problems for family and professional caregivers. Nursing students' ability to meet this challenge was measured using Palmore's (1988) Facts on Aging Quiz, Version 2 (FAQ2) and the Alzheimer's Disease Knowledge (ADK) Test developed by Dieckmann, Zarit, Zarit, and Gatz (1988). No significant difference in ADK Test scores was found for students who had previous personal or educational experiences with AD. However, older students, seniors, and those who reported knowing more about AD had significantly better scores on the ADK Test. Knowledge about AD was not found to be related to knowledge of aging, and subjects as a group were found to exhibit a negative bias toward the elderly as measured by Palmore's FAQ2. PMID- 1313089 TI - The AIDS care dilemma: an exercise in critical thinking. PMID- 1313090 TI - Fear of persons with HIV infection: teaching strategies for helping students cope. PMID- 1313091 TI - Writing recommendations that get results. PMID- 1313092 TI - Create a tradition: teach nurses to share stories. PMID- 1313093 TI - The influence of dietary fiber on proliferation of intestinal mucosal cells in miniature swine may not be mediated primarily by fermentation. AB - Cannulated miniature pigs were used as a model for evaluating the effects of fiber-containing diets on proliferation of colonic epithelial cells. Biopsy specimens taken from the mucosa of the cecum and distal colon were incubated in [3H]thymidine and processed using autoradiography. Digesta from the cecum was analyzed for concentrations of short-chain fatty acids (SCFA), pH and volume. Cellular proliferation at both intestinal sites was influenced by the source or quantity of dietary fiber. These dietary variables also influenced SCFA concentrations and pH of cecal digesta and the volume of contents in the fermentation chamber. Cellular proliferation was not significantly correlated, however, with the quantity of water-soluble dietary fiber consumed, with SCFA concentrations or pH of the cecal digesta, or with the volume of the fermentation chamber. We suggest that the influence of dietary fiber on intestinal cell proliferation cannot be predicted from markers of the fermentation capacity of specific diets, because fiber likely influences intestinal proliferation through several interactive mechanisms, some of which include luminal factors. PMID- 1313094 TI - Occupationally-induced scleroderma. AB - Systemic sclerosis or scleroderma is an uncommon multisystem disease with a reported incidence of 2 to 12 cases per million people per year. The clinical and pathological features can be grouped into three main categories: those related to fibrosis, to vascular abnormalities, and to immunological abnormalities. Cutaneous features dominate the patients' appearance, and Raynaud's phenomenon is an early symptom. A possible association between scleroderma and workers exposed to hand-arm vibration and/or silica has been suggested by reports in the literature since the turn of the century. A further four patients with collagen disease are reported here. Three were occupationally exposed to both hand-arm vibration and silica, the fourth to hand-arm vibration alone. In conjunction with previously reported cases, this supports the hypothesis that collagen disease may be work attributable in hypersusceptible persons. PMID- 1313095 TI - Outbreaks of human enteric adenovirus types 40 and 41 in Houston day care centers. AB - OBJECTIVE: Human enteric adenovirus (EAd) types 40 and 41 cause diarrhea in young children, but little is known about their association with outbreaks of diarrhea in the child care setting. This study evaluated EAd as a cause of outbreaks of diarrhea among infants and toddlers in day care centers. DESIGN: Stool specimens were collected weekly regardless of symptoms during four periods from January 1986 to April 1991, from children 6 to 24 months of age enrolled in prospective studies of diarrhea in day care centers. All diarrhea stool specimens were tested for bacterial enteropathogens, rotavirus, and Giardia lamblia. A total of 131 outbreaks occurred during the study. No etiologic agent was identified in 77 outbreaks. Stool specimens from 75 of these 77 outbreaks and from another 21 outbreaks of diarrhea with a known cause were evaluated for EAd with a monoclonal antibody-based enzyme immunoassay. RESULTS: A total of 4402 stool specimens from 613 children from these 96 outbreaks was tested for EAd. The virus was detected in specimens collected during 10 outbreaks, 3 of which occurred in 1986, 3 in 1988, 1 in 1989, 1 in 1990, and 2 in 1991. Of 249 children, 94 (38%) in these 10 EAd outbreaks were infected with EAd. In 51 children (54%) the infection was symptomatic and in 43 (46%) it was asymptomatic. Outbreaks lasted 7 to 44 days (mean 24.5 days). Duration of EAd excretion ranged from 1 to 14 days (mean 3.9 days), with excretion occurring from 7 days (mean 2.6) before diarrhea began to 11 days (mean 5.3 days) after diarrhea stopped. CONCLUSION: Enteric adenovirus types 40 and 41 are an important cause of outbreaks of diarrhea among children attending day care centers, often involve children in more than one room, and frequently produce asymptomatic infection. PMID- 1313096 TI - A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D. AB - We evaluated the effects of the intravenous administration of anti-D, an immune globulin directed at the D antigen on erythrocytes that is purified from plasma from sensitized persons, on patients with idiopathic thrombocytopenic purpura. To determine the most effective dose, the duration of response, and the side effects of this therapy in children, we performed a multicenter cohort study of escalating doses of intravenously administered anti-D in children aged 1 to 18 years with chronic idiopathic thrombocytopenic purpura, defined as idiopathic thrombocytopenic purpura persisting for more than 6 months with a platelet count of less than 50 x 10(9) cells/L. Twenty-five Rh-positive children received increasing doses of anti-D as follows: day 1, 25 micrograms/kg; day 2, 25 micrograms/kg; day 7, 35 micrograms/kg; day 14, 45 micrograms/kg; and day 21, 55 micrograms/kg. Administration of anti-D was stopped after day 21 or when the platelet count rose to greater than 150 x 10(9) cells/L or the hemoglobin level was 100 gm/L. Platelet count was less than 50 x 10(9) cells/L in all children before treatment. A response was defined as an increase in the platelet count to more than 50 x 10(9)/L and a doubling of the pretreatment platelet count. Of 25 children, 23 (92%) had responses by day 7 of the initial treatment protocol. Eighteen children (72%) had platelet counts greater than 150 x 10(9) cells/L by day 7 after two doses of anti-D. Median duration of response was 5 weeks (range 1 to 24 weeks). Average drop in hemoglobin level was 13.7 gm/L; in one child (a nonresponder) hemoglobin value fell to less than 100 gm/L. No other untoward side effects were seen. Of the 23 children who responded, 21 were retreated with one dose of anti-D when platelet counts returned to baseline values of less than 50 x 10(9) cells/L; all but three of the children who underwent retreatment showed a response the second time. Sixteen children continued to receive intermittent anti D therapy after completion of the study, and all continued to have excellent responses. We conclude that anti-D is a safe, effective, and relatively inexpensive therapy for childhood chronic idiopathic thrombocytopenic purpura. PMID- 1313097 TI - Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2. AB - We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of illness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections. PMID- 1313098 TI - Acyclovir treatment of varicella in otherwise healthy adolescents. The Collaborative Acyclovir Varicella Study Group. AB - STUDY OBJECTIVE: To determine whether orally administered acyclovir is of therapeutic benefit for varicella in otherwise healthy adolescents, and to compare the severity of the disease in adolescents with that in younger children. DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial. SETTING: Patients' homes and university hospital clinics. PATIENTS: Sixty-eight adolescents between 13 and 18 years of age with varicella entered the study. Of the 62 adolescents with laboratory-confirmed varicella who were included in the final analysis, 31 received acyclovir and 31 received placebo. INTERVENTIONS: Placebo or an 800 mg acyclovir tablet was given orally four times daily for 5 days, beginning within 24 hours of onset of rash. MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients had significant reductions in times to cessation of new lesion formation (p less than 0.001), maximum number of lesions (p = 0.019), and defervescence (p = 0.045). Mean constitutional illness score was significantly reduced on day 4 (0.5 vs 1.5, p = 0.05), as was the mean number of residual hypopigmented lesions present on 28-day follow-up examination (22.7 vs 92.7, p = 0.018). Two complications, both bacterial superinfections, occurred in placebo recipients. Adverse experiences and varicella-zoster virus antibody titers measured 28 days after enrollment were similar in both treatment groups. Comparison of placebo recipients with children 2 to 12 years of age participating in a companion study indicated that varicella is more severe in adolescents: mean maximum total lesions (421 vs 347, p = 0.003), mean maximum constitutional illness score (3.1 vs 2.2, p = 0.032), and mean number of residual lesions (92.7 vs 33.2, p = 0.01) were all greater in the adolescent population. CONCLUSIONS: Oral acyclovir therapy is safe and effective for treatment of varicella in otherwise healthy adolescents; this may be an appropriate subgroup for treatment with antiviral drugs because the disease is more severe in them than in younger children. PMID- 1313099 TI - Wilm's tumor consisting entirely of a botryoid intrapelvic renal mass. PMID- 1313100 TI - Gingival crevicular fluid concentration and side effects of minocycline: a comparison of two dose regimens. AB - The purpose of this study was to conduct a direct comparison of two dose regimens of minocycline to determine 1) whether they achieved crevicular fluid concentrations in a therapeutic range; and 2) the frequency of side effects. In a double-blind design, 30 patients divided into 2 groups were given either 100 mg minocycline or 200 mg minocycline per day for an 8-day period. The concentration of minocycline in the gingival clevicular fluid (GCF) at 8 days was 4.77 micrograms/ml for the 100 mg a day group and 5.97 micrograms/ml for the 200 mg a day group and at 15 days was 4.30 micrograms/ml for the 100 mg a day group and 4.17 micrograms/ml for the 200 mg a day group. There was no significant difference in the antibiotic concentration in the gingival crevicular fluid between the 2 groups. Reported adverse experiences to the minocycline were greater in the 200 mg a day group. Short-term changes in periodontal health as measured by plaque index, gingival index, pocket depth, and bleeding upon probing showed improvements in all parameters over the 15 day period. There were no significant differences in these parameters between the 100 mg a day and 200 mg a day group. At 8 days reduced levels of Porphyromonas gingivalis and Prevotella intermedia were achieved but they were not eliminated from infected subgingival sites in either group. Achieving bacteriostatic concentrations of GCF, fewer side effects, and the potential for better compliance suggests that a single daily dose of 100 mg minocycline should now be investigated for its efficacy in managing periodontal infections manifesting as periodontitis. PMID- 1313101 TI - In vitro platelet serotonin secretion and inhibition on variously treated root surfaces. AB - Platelet degranulation can result in the release of a variety of factors which are chemotactic, mitogenic, and angiogenic, making platelets extremely important in the regulation of the repair process. This study examines how various types of root surfaces affect platelet deposition and the release of serotonin from dense granules. In addition, experiments were performed to evaluate the effects of the cyclo-oxygenase inhibitor, indomethacin, on platelet deposition and dense granule release. Roots from freshly extracted teeth from sites with periodontal disease (PD) and from healthy sites were sectioned and had the following surface conditions: 1) periodontal ligament present; 2) PD; 3) PD, root planed; 4) PD, root planed and demineralized; and 5) condition 4 treated with collagenase. In addition, rabbit calcaneal tendon collagen was used. All samples were incubated with platelets labeled with both 111Indium and 14C serotonin, with and without the addition of indomethacin. It was observed that the greatest number of platelets deposited on the tendon collagen. Furthermore, serotonin release occurred on all samples except PD and indomethacin partially inhibited platelet deposition on all samples except tendon collagen. Finally, indomethacin inhibited serotonin release on all surfaces. These results suggest that attachment of platelets to the root surface is facilitated by metabolism through the cyclo oxygenase pathway and that limited platelet deposition can occur in the absence of dense body release. PMID- 1313102 TI - Assessment of the relative cytotoxicity of Porphyromonas gingivalis cells, products, and components on human epithelial cell lines. AB - Established human cell lines derived from a transitional cell carcinoma (J82), a squamous carcinoma (SCaBER), and a normal urothelium (HCV-29) were used to assess the relative cytotoxicity and tissue specificity of putative virulence determinants of P. gingivalis W83. Intact cells of W83 had no effect on any of the cell lines, whereas disrupted cells caused extensive cytotoxicity particularly to monolayers of HCV-29 and J82. The purified cysteine proteinase, gingivain, caused marked disruption of the basement membrane of the SCaBER monolayers but had no cytotoxic effects. Use of the thiol-inhibitor, 2,2' dipyridyl disulphide revealed that the effects observed with the vesicles and the culture supernatant were due to the presence of the cysteine proteinase. The attachment of vesicles to the SCaBER cells was evident in electron micrographs. Short-chain volatile fatty acids added in concentrations equivalent to those present in the culture supernatant had no effect on any of the cell lines tested. Culture supernatants obtained from high speed centrifugation (150,000 x g) showed no cytotoxic effects. This was in marked contrast to the supernatant obtained by lower sedimentation (18,000 x g), which damaged all monolayers tested. These results suggest that these cell lines are potentially useful for assessing putative virulence determinants of P. gingivalis and other periodontal pathogens. PMID- 1313103 TI - Microbiological and clinical results of metronidazole plus amoxicillin therapy in Actinobacillus actinomycetemcomitans-associated periodontitis. AB - We report on the microbiological and clinical effects of mechanical debridement in combination with metronidazole plus amoxicillin therapy in 118 patients with Actinobacillus actinomycetemcomitans-associated periodontitis. Patients were categorized into 3 groups: 28 had localized periodontitis; 50 had generalized periodontitis, and 40 had refractory periodontitis. After initial treatment and metronidazole plus amoxicillin therapy 114 of 118 (96.6%) patients had no detectable A. actinomycetemcomitans. Significant reduction in pocket probing depth and gain of clinical attachment were achieved in almost all patients. Four patients were still positive for A. actinomycetemcomitans after therapy. Metronidazole resistance (MIC greater than 25 micrograms/ml) was observed in 2 of 4 strains from these patients. Patients still positive for A. actinomycetemcomitans or Porphyromonas gingivalis showed a significant higher bleeding tendency after therapy. It was concluded that mechanical periodontal treatment in combination with the metronidazole plus amoxicillin therapy is effective for subgingival suppression of A. actinomycetemcomitans in patients with severe periodontitis. PMID- 1313104 TI - Dentifrice abrasivity and cervical dentinal hypersensitivity. Results 12 weeks following cessation of 8 weeks' supervised use. AB - Following an 8-week controlled investigation of 2 strontium chloride hexahydrate dentifrices (SCH) of differing abrasivity, 2 groups of 20 subjects each, with cervical dentinal hypersensitivity, were re-examined at 20 weeks; that is, 12 weeks after the active period. The examination procedures were conducted in the same manner as in the main clinical trial. Sensitivity levels were assessed by 2 instrument methods: tactile (Yeaple probe), and cold air (dental air syringe), and by subjective perception of pain by means of a Visual Analogue Scale. The results from these methods of assessment demonstrated that 12 weeks following the cessation of 8 weeks' controlled use of standard and low abrasive SCH dentifrices, sensitivity levels reversed on slightly in both groups and, overall, sensitivity remained significantly lower than at baseline. The abrasivity of the dentifrice did not affect the desensitivity activity. PMID- 1313105 TI - Periodontal repair in dogs: effect of a composite graft protocol on healing in supraalveolar periodontal defects. AB - This study evaluated the effect of a composite graft as an adjunct to gingival flap surgery in induced chronic supraalveolar periodontal defects in the mandibular premolar region in beagle dogs. The vertical dimension of the defects, measured from the cemento-enamel junction to the alveolar bone, approximated 5 mm. Root surface treatment in quadrants receiving the graft protocol included conditioning with both critic acid and tetracycline. The composite graft (including: hydroxyapatite, freeze-dried decalcified bone, tetracycline, and fibronectin) was then fitted to the defects. Flaps were placed and sutured to cover most of the crowns of the teeth but the tips of the cusps. The root surfaces in contralateral jaw quadrants were conditioned with critic acid and the flaps similarly placed and sutured. Dogs were sacrificed 6 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histometric analysis. Connective tissue repair to the root surface in teeth treated with the graft protocol approximated 60% of the defect height. Connective tissue repair in teeth treated with citric acid only was significantly greater and averaged 98% of the defect height (P less than or equal to 0.01). Cementum formation was limited following both treatments (approximately 6% of the defect height). Bone regeneration was significantly smaller in grafted sites than in sites treated with citric acid only (approximately 2% and 10% of the defect height, respectively; P less than or equal to 0.05). Root resorption was observed in almost all teeth. Ankylosis was present in two citric acid-treated specimens, both from the same dog.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313106 TI - Humoral antibody responses in periodontal disease. AB - Several forms of periodontal disease are considered to be infectious diseases with associated specific bacteria. This study examined the humoral antibody levels as assayed by ELISA to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in adult periodontitis (AP), localized juvenile periodontitis (LJP), rapidly progressive periodontitis (RPP), and in periodontally healthy subjects (HS). Sixty-two of the 64 (96.9%) patients had significantly elevated antibody levels to at least one of the three organisms. Elevated levels of antibodies to P. gingivalis occurred in 82.8% of the RPP, LJP, and AP patients with all 3 disease groups showing greater responses than HS controls. Antibodies to A. actinomycetemcomitans were found in 59.4% of the RPP, LJP, and AP patients and were significantly higher in both LJP and RPP patients. Only 21.9% of the RPP, LJP, and AP patients showed elevated levels to P. intermedia with only significantly higher levels in the RPP and LJP groups. Antibodies to A. actinomycetemcomitans and P. intermedia were rarely found alone (only 5.1% and 2.6% of the patients respectively) but were usually accompanied by P. gingivalis. These results suggest that one or more combinations of these 3 bacteria may play a role in the pathogenesis of these forms of periodontal disease. PMID- 1313107 TI - Evaluation of oral bacteria as risk indicators for periodontitis in older adults. AB - The prevalence of people and sites with attachment loss, pocket depth, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis are described for a random sample of 366 black and 297 white community dwelling adults, aged 65 or over, residing in five counties in North Carolina. In addition, relationships between sites harboring these microorganisms and loss of attachment (LA) and pocket depth (PD) are presented in a manner that considers the lack of independence of sites within each person. Pocket depths and recession were measured on all teeth by trained examiners during household visits. Immunofluorescent assays for A. actinomycetecomitans, P. intermedia, and P. gingivalis were conducted on subgingival plaque samples obtained from the mesiobuccal aspect of the four first molar teeth using paper points. The prevalences of A. actinomycetemcomitans, P. intermedia, and P. gingivalis were greater in blacks than in whites. The most striking difference was seen for P. gingivalis, which was found in 38.8% of blacks and 9.4% of whites. Similar relationships were found when the percent of sites with these organisms were assessed. Blacks with P. gingivalis or P. intermedia had a higher prevalence of sites with LA greater than or equal to 7 mm as compared to blacks not infected with P. gingivalis or P. intermedia. The same was true for whites. Similar relationships between P. gingivalis or P. intermedia and PD greater than or equal to 6 mm were found for both blacks and whites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313108 TI - CoMFA analysis of the interactions of antipicornavirus compounds in the binding pocket of human rhinovirus-14. AB - A CoMFA analysis of eight compounds related to disoxaril whose X-ray structures bound to HRV-14 had been determined resulted in a strong positive correlation of activity with steric effects of the compounds, particularly toward the pore end of the compound binding site, and no correlation with electrostatic effects. These results confirm what had been previously found, that the activity of these compounds was highly dependent upon their hydrophobic nature as expressed by log p. The CoMFA study also confirmed the results from the comparison of a series of active and inactive compounds using volume maps which showed that bulk at the pore end of the molecule was conducive to high levels of antiviral activity while excessive bulk around the ring led to poor activity. PMID- 1313109 TI - Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors. AB - The alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic properties of the 2-(3,4 dihydroxyphenyl)morpholines 3 and 4 (2-DPMs), of the 3-(3,4-dihydroxyphenyl)-3 piperidinols 5 and 6 (3-DPPs), and of the trans-2-amino-5,6 dihydroxytetrahydronaphthalen-1-ols 7 and 8 and the trans-2-amino-6,7 dihydroxytetrahydronaphthalen-1-ols 9 and 10 (2-ADTNs) were evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations and compared with those of norepinephrine (NE, 1) and isoprenaline (ISO, 2). Through a comparison of the stereostructures of the compounds examined with their biopharmacological properties, it was possible to revise previously proposed molecular models for the direct activation of alpha- and beta-adrenergic receptors. The revised models (A-C) provided information about the conformational requirements of adrenergic drugs, which substantially fit in with the results of several published studies involving conformationally-restricted adrenoceptor agonists. The different position of the catecholic hydroxyl groups in model B, which refers to the alpha 2 receptors, and in model C, which refers to the beta receptors, confirms the importance of the rotameric position of the aromatic ring of catecholamines in the interaction with the alpha- and beta-adrenergic receptor. PMID- 1313110 TI - (H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate. AB - [(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies. PMID- 1313111 TI - Susceptibility of selected strains of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) to chikungunya virus. AB - The relative susceptibility of selected strains of Aedes aegypti (L.) and Aedes albopictus (Skuse) fed on a viremic monkey to infection with chikungunya virus was determined. Infection rates were consistently higher in 10 strains of Ae. albopictus tested than in 7 strains of Ae. aegypti tested, regardless of the geographic location from which the strains originated or the dose of virus ingested. Similarly, virus dissemination rates were higher in the Ae. albopictus strains compared with the Ae. aegypti strains. For nearly all (11 of 12) strains tested of both species, groups of mosquitoes with one or more females with a disseminated infection transmitted virus by bite to weanling mice. Based on these studies, Ae. albopictus appears to be a more competent laboratory vector of chikungunya virus than does Ae. aegypti. PMID- 1313112 TI - An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations. AB - We report familial adenomatous polyposis coli (FAPC) with epidermoid cysts, osteomata, and areas of congenital hypertrophy of the retinal pigment epithelium (CHRPEs) in a male patient and his maternal aunt, both of whom suffered a mild to moderate degree of mental handicap. Both had an interstitial deletion of the long arm of chromosome 5 (del(5)(q22q23.2)). Two other normal family members had the underlying direct insertion of chromosome 5(dir ins(5)(q31.3q22q23.2)). Molecular genetic and fluorescent hybridisation studies have shown that loci D5S37 and D5S98 are outside the deletion whereas loci detected by probes EF5.44 and YN5.48 are lost. As expected, the molecular analyses indicate loss of one allele at the MCC and APC loci. The APC gene is located within band 5q22. Familial direct insertions should be considered as a cause of recurrent microdeletion syndromes. PMID- 1313113 TI - Regulation of endogenous and expressed Na+/K+ pumps in Xenopus oocytes by membrane potential and stimulation of protein kinases. AB - Modulation of the current generated by the Na+/K+ pump by membrane potential and protein kinases was investigated in oocytes of Xenopus laevis. In addition to a positive slope region in the current-voltage (I-V) relationship of the Na+/K+ pump, a negative slope region has been described in these cells (Lafaire & Schwarz, 1986) and has been attributed to a voltage-dependent apparent Km value for pump stimulation by external [K+] (Rakowski et al., 1991). To study this feature in more detail, Xenopus oocytes were used for comparative analysis of the negative slope of the I-V relationship of the endogenous Na+/K+ pump and of the Na+/K+ pump of the electric organ of Torpedo californica expressed in the oocytes. The effects of stimulation of protein kinases A and C on the negative slope were also analyzed. To investigate the negative slope over a wide potential range, experiments were performed in Na(+)-free solution and in the presence of high concentrations of Ba2+ and tetraethylammonium, to block all nonpump related K(+)-sensitive currents. Pump currents and pump-mediated fluxes were determined as differences of currents or fluxes in solutions with and without extracellular K+. The voltage dependence of the Km value for stimulation of the Na+/K+ pump by external [K+] shows significant species differences. Over the entire voltage range from -140 to +20 mV, the Km value for the Na+/K+ pump of Torpedo electroplax is substantially higher than for the endogenous pump and exhibits more pronounced voltage dependence. For the Xenopus pump, the voltage dependence can be described by voltage-dependent stimulation by external [K+] and can be interpreted by voltage-dependent K+ binding, assuming that an effective charge between 0.37 and 0.56 of an elementary charge is moved in the electrical field. An analogous evaluation of the voltage dependence of the Torpedo pump requires the assumption of movement of two effective charges of 0.16 and 1.0 of an elementary charge. Application of 1,2-dioctanoyl-sn-glycerol (diC8, 10-50 microM), which is known to stimulate protein kinase C, reduces the maximum activity of the Xenopus pumps in the oocyte membrane by 40% and modulates the voltage dependence of K+ stimulation. For the endogenous Xenopus pump, the apparent effective charge increased from 0.37 to 0.51 of elementary charge and the apparent Km at 0 mV increased from 0.46 to 0.83 mM. For the Torpedo pump, one of the apparent effective charges increased from 1.0 to 2.5 of elementary charge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1313114 TI - Electrogenic proton secretion in the hindgut of the desert locust, Schistocerca gregaria. AB - The cellular mechanisms responsible for rectal acidification in the desert locust, Schistocerca gregaria, were investigated in isolated recta mounted as flat sheets in modified Ussing chambers. Previous studies conducted in the nominal absence of exogenous CO2 and HCO3- suggested that the acidification was due to a proton-secretory rather than bicarbonate-reabsorptive mechanism (Thomson, R.B., Speight, J.D., Phillips, J.E. 1988. J. Insect Physiol. 34:829 837). This conclusion was confirmed in the present study by demonstrating that metabolic CO2 could not contribute sufficient HCO3- to the lumen to account for the rates of rectal acidification observed under the nominally CO2/HCO3(-)-free conditions used in these investigations. Rates of luminal acidification (JH+) were completely unaffected by changes in contraluminal pH, but could be progressively reduced (and eventually abolished) by imposition of either transepithelial pH gradients (lumen acid) or transepithelial electrical gradients (lumen positive). Under short-circuit current conditions, the bulk of JH+ was not dependent on Na+, K+, Cl-, Mg2+, or Ca2+ and was due to a primary electrogenic proton translocating mechanism located on the apical membrane. A small component (10-16%) of JH+ measured under these conditions could be attributed to an apical amiloride-inhibitable Na+/H+ exchange mechanism. PMID- 1313115 TI - Serum independence of low K+ induction of Na,K-ATPase: possible role of c-fos. AB - Cultured ARL15 cells respond to abnormally low extracellular K+ concentrations by increasing the abundance of Na,K-ATPase (the Na/K pump). This response is preceded by significant increases in the mRNAs of the alpha 1 and beta 1 subunits of this enzyme, implying transcriptional or post-transcriptional regulation in the response. The present study concerned the possible participation of serum factors in low K+ induction of Na,K-ATPase. In normal K+ (4.5 mM) or low K+ (0.68 mM) the presence of 10% calf serum had no effect on Na,K-ATPase activity. The serum independence of the response to low K+ raised the possibility that low K+ may itself elicit a "growth" response. Accordingly, the effect of low K+ on mRNA abundances of four proto-oncogenes (c-fos, c-myc, c-jun and c-ski) was evaluated in the early phase of the response by quantitative Northern blot analysis. The mRNA for c-fos was transiently elevated by low K+, with a peak at 30 min. In contrast, low K+ had no measurable effect on the abundances of c-myc, c-jun and c ski, for up to 2 hr of exposure. The early elevation of c-fos mRNA makes it a candidate mediator in this signal-transduction pathway. Induction of c-fos mRNA by the phorbol ester, PMA, or by dioctanoyl glycerol, however, had no effect on Na,K-ATPase activity. These results indicate that an increase in c-fos mRNA alone is not sufficient to induce Na,K-ATPase. Whether induction of c-fos is necessary for the response to low K+ remains to be determined in future studies. PMID- 1313116 TI - Prevention of urinary tract infection and bacteremia following transurethral surgery: oral lomefloxacin compared to parenteral cefotaxime. AB - A multicenter, randomized, open label study compared the safety and efficacy of a single dose of oral lomefloxacin, a broad-spectrum antimicrobial agent of the quinolone class, to a single parenteral dose of cefotaxime, a third generation cephalosporin, for prophylaxis in transurethral surgery. Of the 230 patients initially recruited 182 were considered evaluable: 92 in the lomefloxacin group and 90 in the cefotaxime group. Both study groups were well balanced with respect to demographics and transurethral procedures. Efficacy and safety were evaluated with urine cultures, clinical laboratory evaluations and monitoring of adverse events. The success rate among the lomefloxacin patients was 98% versus 94% in the cefotaxime patients. The difference was not statistically significant. Adverse events, regardless of attributability, were reported by 16% of the lomefloxacin patients and 17% of the cefotaxime patients, respectively. Our results indicate efficacy and safety profiles of lomefloxacin equivalent to cefotaxime. Lomefloxacin has the economic advantage of an oral route of administration compared to the parenteral route of cefotaxime for prophylaxis in transurethral genitourinary procedures. PMID- 1313117 TI - Vaccine information pamphlets here, but some physicians react strongly. PMID- 1313118 TI - Aplastic anemia and viral hepatitis. Non-A, Non-B, Non-C? AB - OBJECTIVE: To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection. DESIGN: Case series. SETTING: Tertiary referral centers in the United States, Japan, Italy, and Germany. PATIENTS: Twenty-eight patients with onset of aplastic anemia within 90 days after seeking medical attention for jaundice, or having serum transaminase levels 150% or more of normal (hepatitis-associated aplasia patients) and three patients who developed aplastic anemia following liver transplantation for non-A, non-B hepatitis. OUTCOME MEASURES: Presence of hepatitis C in serum, bone marrow, and liver samples, detected by the polymerase chain reaction; antibody testing; and percentage of activated peripheral cytotoxic T lymphocytes determined by immunophenotyping. RESULTS: Hepatitis ribonucleic acid was present in the serum samples of 10 (36%) patients with hepatitis-associated aplasia. However, hepatitis C virus viremia was associated with transfusions received after the onset of aplasia: seven (58%) of 12 patients with hepatitis-associated aplasia who had received 21 or more units of blood products at the time of serum sampling were viremic, compared with only three (19%) of 16 patients with hepatitis-associated aplasia who had received 20 or less units of blood products (P less than .05). Hepatitis C virus was not found in blood and bone marrow samples of three National Institutes of Health case patients tested at the time of diagnosis. None of three livers from non-A, non-B hepatitis patients who developed aplastic anemia after liver transplantation contained hepatitis C virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three- to 20-fold early in the course of hepatitis-associated aplasia. CONCLUSIONS: Our results implicate a novel, non-A, non-B, and non-C agent in both hepatitis-associated aplasia and fulminant hepatitis. PMID- 1313119 TI - Enhanced myocardial adenylate cyclase activity in spontaneously hypertensive rats. AB - This study was designed to clarify the state of beta-adrenergic signal transduction and the disordered level of its transduction in hypertensive hearts, using myocardium from spontaneously hypertensive rats (SHR) as a generic model of essential hypertension. Beta-adrenergic receptor binding sites and dissociation constants in the extracted membranes of adult (70-100 days of age) SHR heart were not significantly different from those of Wistar-Kyoto (WKY) rats, the non hypertensive control. The adenylate cyclase activities stimulated by isoproterenol with GTP, NaF and forskolin were significantly higher in SHR compared to those in WKY. To determine whether differences in signal transduction are natural or are a result of hypertension, we evaluated chronotropic responses in cultured cells of fetal hearts which had not been exposed to hypertension. Fetal cardiac muscle cells of SHR were more sensitive than WKY to isoproterenol stimulation over a wide concentration range. However, there were no statistically significant differences between these two strains with respect to the density of binding sites. These results suggest that in the transduction of adrenergic signals, alterations distal to the beta-receptors are present in the adult hearts of hypertensive rats, and, that the adrenergic signal transduction is already exaggerated in the pre-hypertensive fetal stage. PMID- 1313120 TI - [Prostaglandin E1 infusion fails to inhibit the increase of serum granulocyte elastase and myeloperoxidase and the decrease of plasma angiotensin converting enzyme in patients undergoing open-heart surgery]. AB - We studied whether prostaglandin E1 (PGE1) could inhibit the increase of serum granulocyte elastase (GEL) and myeloperoxidase (MPO), and the decrease of plasma angiotensin converting enzyme (ACE) induced by oxygenator in 19 patients undergoing open-heart surgery. The patients were randomly allocated into 2 groups: one group (PGE1 group, n = 9) received a continuous infusion of PGE1 at a rate of 30 ng.kg-1.min-1 during cardiopulmonary bypass (CPB), and the other group (control group, n = 10) received saline infusion. GEL, MPO and ACE were measured serially at 8 points: before induction of anesthesia (as baseline), immediately before initiation of CPB, 10 min after initiation, 60 min after initiation, immediately after the end of CPB, 60 min after CPB, 120 min after CPB, and on the first postoperative day. Serum levels of GEL and MPO during 120 min after the end of CPB in both groups increased significantly compared with the baseline values. There was no significant difference between the two groups. Plasma levels of ACE in both groups decreased significantly immediately after the end of CPB compared with values taken 10 min after the initiation of CPB. There was no significant difference between the groups. We conclude that the infusion of PGE1 30 ng.kg 1.min-1 failed to inhibit the increase of GEL as well as MPO, and the decrease of ACE. PMID- 1313121 TI - Regulation of Na+ channels in the cortical collecting duct by AVP and mineralocorticoids. AB - A variety of experimental approaches have shown that AVP and mineralocorticoids stimulate Na+ transport through their effects on the number and kinetic properties of amiloride-sensitive Na+ channels in the apical membrane. The different mechanisms by which AVP and mineralocorticoid act on the Na+ channel provide a basis for synergism in their actions, perhaps by a scheme such as that proposed in Figure 5. However, the details of this interaction will require a better understanding of the molecular details involved in activating quiescent channels, increasing their open probability, and reorientating or inserting channels to an operational position in the apical membrane. Electrophysiological and biochemical approaches have gone a long way toward elucidating some of these molecular details. But the latter approach in particular has indicated that the Na+ channel may have multiple regulatory subunits and thus be a target for several intracellular second messengers and autacoids other than those involved in the actions of AVP and aldosterone. The challenges for future research in this area are multiple. It seems likely that the primary amino acid sequence of the channel subunits will soon become available from cloning and sequencing approaches, but the application of this knowledge to understanding how the subunits are integrated into the complete protein and mediate regulatory signals will be a formidable task. It will be important to determine the normal extracellular signals (other than aldosterone and AVP) and the associated intracellular second messengers that alter channel activity. It will also be important to understand how some species such as the rabbit may "turn off" the stimulatory effect of AVP on Na+ reabsorption in the CCD, and how this regulatory process is altered when these cells are cultured. At the whole animal level, it will also be important to investigate whether changes in one or more of the normal regulatory pathways that impinge on the Na+ channel might be involved in a diminished ability to excrete a salt load, as is observed in some models of hypertension. All of these issues need to be understood at the molecular level, and it seems likely they will provide exciting physiological insights at all levels. PMID- 1313122 TI - Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model. AB - Increasing evidence supports a role of glomerular cell proliferation in the development of focal or diffuse glomerulosclerosis. This study investigates the chronology and sequence of cellular events that precede glomerulosclerosis in 5/6 nephrectomized rats. Within three days of renal ablation, a phenotypic switch occurred in which some mesangial cells expressed alpha-smooth muscle actin. This was followed by proliferation of mesangial cells, and to a lesser degree endothelial cells from day 5 to week 4 as detected by immunostaining for the proliferating cell nuclear antigen (PCNA). Glomerular cell proliferation was accompanied by increased immunohistochemical expression of PDGF B-chain. In situ hybridization showed no glomerular PDGF B-chain mRNA expression at the induction of proliferation (day 5), and a marked increase between week 1 and 4 in operated rats. In parallel, increased expression of PDGF receptor beta-subunit protein and mRNA was demonstrated by immunohistochemistry and Northern analysis of total glomerular RNA. The onset of glomerular cell proliferation was also associated with mild glomerular platelet accumulation (as defined by 111In-labelled platelet studies) as well as with fibrinogen deposition. Proteinuria, glomerular sclerotic changes, and leukocyte infiltration all followed cell proliferation. The glomerular leukocyte infiltrate consisted of monocytes/macrophages and increased markedly at week 10 in rats with renal ablation. Thus, our results suggest that in the remnant kidney model: 1) proliferation of intrinsic glomerular cells precedes glomerulosclerosis; 2) proliferation may be initiated by degranulating platelets and sustained by PDGF released from intrinsic glomerular cells; and 3) glomerular monocyte/macrophage infiltration occurs after the proliferation, and may possibly contribute to the development of glomerular sclerotic changes. PMID- 1313123 TI - Regulation of endothelin-1 production in cultured rat mesangial cells. AB - We investigated the regulatory mechanisms of endothelin (ET)-1 production in cultured rat mesangial cells (MC), with a special focus on the roles of protein kinase A (PKA)- and protein kinase C (PKC)-mediated signaling systems. Vasoactive agents and growth promoting factors, including platelet-derived growth factor, vasopressin and thrombin, which act through receptors coupled to the phospholipase C-mediated signaling system, as well as phorbol ester and fetal calf serum stimulated ET-1 production. This effect was attenuated in PKC-depleted or H-7 (a PKC inhibitor) treated MC. On the other hand, an increase in intracellular cyclic AMP by forskolin or beta-adrenergic agonist, isoproterenol, which act as anti-mitogenic agents, inhibited serum-stimulated ET-1 production. In addition this effect was mimicked by the addition of 8-bromo-cyclic AMP to the medium. The effect of isoproterenol was abolished by propranolol. H-8, a PKA inhibitor, attenuated the inhibitory effect of forskolin. These findings suggest that ET-1 production in MC is regulated by interaction of both positive and negative signals mediated by PKC- and PKA-dependent mechanisms. PMID- 1313124 TI - Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells. AB - Anti-myeloperoxidase autoantibodies are found in association with idiopathic necrotizing glomerulonephritis and systemic vasculitis. It is not known if their presence is an epiphenomen or an integral part of the pathogenic process. To further delineate their hypothesized pathogenicity, we studied their ability to stimulate neutrophils to damage human umbilical vein endothelial cells in vitro. Anti-myeloperoxidase antibodies from human, rabbit and mouse sources were utilized. These antibodies stimulated neutrophils to damage endothelial cells as determined by 51Cr release. The effect was dependent on priming the neutrophils with tumor necrosis factor-alpha, and further enhanced with the addition of endotoxin. The amount of endothelial cell damage was dependent on the dose of anti-myeloperoxidase, the source of the neutrophils, the concentration of TNF, and the presence of endotoxin. Under identical conditions, control antibodies did not stimulate neutrophils to damage endothelial cells. The effect was confirmed by labeling the endothelial cells with 3H-adenine which yielded the same results. These results provide further in vitro evidence that anti-myeloperoxidase autoantibodies may play a significant role in the pathogenesis of idiopathic pauci-immune glomerulonephritis and vasculitis. PMID- 1313125 TI - A cytochemical procedure for determination of Na+,K(+)-ATPase activity in MDCK cells. PMID- 1313126 TI - Detection of Epstein-Barr virus genome in natural-killer-like cell line, YT. AB - YT cells, originally reported as a natural-killer-like (NK-like) lymphoid cell line, were investigated for Epstein-Barr virus (EBV) genome, gene rearrangement for T-cell receptor (TCR), phenotype and function. The YT cells of the original batch (YT-0) and two subclones (YT2C2 and YTC3) expressed EBV-associated nuclear antigen, and the BamHI-digested DNA showed the 3.4 kb hybridizing band with the BamHIW probe of EBV DNA in Southern blot analysis. When tested with latent infection membrane protein probe, an identical hybridizing band was shared, indicating that all three sources of YT cells were of monoclonal derivation in terms of the terminal repeat junctional structure of EBV DNA, and that the original YT cells had been infected with EBV before the isolation of the two subclones. The cell-surface antigen analysis revealed the expression of CD7, CD28, CD30, CD45R0, TLiSA and S6F1 antigen besides the originally recorded CD25, CD56 and HLA-DR antigen. Gene rearrangement analysis showed the germ-line genotype, including TCR gamma and delta as well as beta chain. The Northern blot study using the CD3 epsilon and CD3 delta chain gene probes revealed CD3 epsilon, but not CD3 delta RNA. The YT-0 cells exhibited NK and antibody-dependent cellular cytotoxicity activity, but the YT2C2 and YTC3 cells did not. It was not resolved whether the fresh neoplastic NK-like cells of the YT-cell donor carry EBV genome, but YT cells, the first lymphoid cell line found to have EBV genome and non-B lymphoid properties, are valuable for investigating the relationship between EBV and human non-B lymphoid hematopoietic cells. PMID- 1313127 TI - Establishment of a new human B-cell line (BONNA-12) with trisomy 9 and trisomy 12 chromosomal abnormality. PMID- 1313128 TI - [A multisecretory pancreatic tumor and associated hypouricemia]. PMID- 1313129 TI - [Acute hepatitis C. A clinical and epidemiological study]. AB - BACKGROUND: The discovery of the hepatitis C virus (HCV) and the possibility of determining anti-HCV serum antibodies has permitted greater etiological, clinical and epidemiological knowledge of non A non B hepatitis (NANB). METHODS: The clinical and epidemiological characteristics of 47 patients with acute hepatitis C were studied. Diagnosis was based on compatible clinical and analytical picture as well as positivity of the anti-HCV antibodies. RESULTS: Thirty-eight percent of the patients were intravenous drug abusers (IVDA). Thirty-four percent had transfusion antecedents and the remaining were sporadic forms of which 3 cases corresponded to health care workers. The study of other viral markers demonstrated that only in the IVDA collective did infections by hepatitis B and delta (HBV and HDV) and by the human immunodeficiency virus (HIV) coexist. Anti HCV antibodies were detected between 15 days and 8 months (mean 38 +/- 74 days) of clinic initiation; with no differences being found regarding the form of contagion. The incubation period of transfused patients was 50 +/- 15 days. In 2 cases the disease followed a biphasic course, in 4 patients a cholestatic profile was observed, and in 12 the hepatitis was anicteric. In 28% of the cases controlled over 6 months the disease autolimited itself and 72% developed active chronic hepatitis. CONCLUSIONS: Most cases of acute hepatitis C are of intravenous origin with a prolonged period of anti-HCV positivization. No differences exist in the clinical picture of the disease regarding the form of contagion and the great tendency to chronicity of hepatitis C is confirmed, regardless of the mechanisms of acquiring the disease. PMID- 1313130 TI - [Rapid increase in the incidence of respiratory aspergillosis. Improved diagnosis and more aggressive treatment for better prognosis]. PMID- 1313131 TI - Synthesis and binding characteristics of the highly delta-specific new tritiated opioid peptide, [3H]deltorphin II. AB - A radiolabelled form of deltorphin II was synthesized by catalytic tritiation using [p-IPhe3]-deltorphin II as a precursor. The ligand labels rat brain membranes with a Kd value of 1.9 nM, and the Bmax was found to be 92 fmol/mg protein. This new tritiated ligand exhibits high affinity for the delta opioid binding site, whereas its binding to the mu type is weak and extremely low for the kappa type. Mu/delta and kappa/delta selectivity ratios were about 900 and 10,000, respectively. The highly delta selective binding properties of this new radioligand suggest that it could serve as an excellent tool for investigating the delta opioid receptors in various species. PMID- 1313132 TI - Regulation of [3H]nitrendipine binding by phospholipases A2 and C through direct and GTP-sensitive mechanisms. AB - We compared the effects of Phospholipases A2, C, B and D on [3H]nitrendipine binding to hamster cardiac membranes, in the absence and presence of ATP or GTP. Phospholipase A2, competitively inhibited [3H]nitrendipine binding to hamster cardiac membranes unchanged by ATP or GTP (Ki = 5 ng/ml); as evidenced by complete and reversible displacement of [3H]nitrendipine binding and increase in KD on Scatchard analyses. Phospholipase C also completely inhibited [3H]nitrendipine binding to hamster cardiac membranes (Ki = 5 micrograms/ml) with a decrease in Bmax and no change in KD on Scatchard analyses. The addition of GTP alone inhibited the PLC effect in EGTA-treated membranes. The addition of GTP with either CaCl2 or ATP or both resulted in an equal and opposite enhancement of the PLC effect. Phospholipases B and D had no effect on [3H]nitrendipine binding. These data support: (1) Direct effect of PLA2 on dihydropyridine binding. (2) Indirect regulation of dihydropyridine binding by Phospholipase C through a GTP and ATP-sensitive mechanism. PMID- 1313133 TI - Characterization of [3H]naltrindole binding to delta opioid receptors in rat brain. AB - [3H]Naltrindole binding characteristics were determined using homogenized rat brain tissue. Saturation binding studies at 25 degrees C measured an equilibrium dissociation constant (Kd) value of 37.0 +/- 3.0 pM and a receptor density (Bmax) value of 63.4 +/- 2.0 fmol/mg protein. Association binding studies showed that equilibrium was reached within 90 min at a radioligand concentration of 30 pM. Naltrindole, as well as the ligands selective for delta (delta) opioid receptors, such as pCI-DPDPE and Deltorphin II inhibited [3H]naltrindole binding with nanomolar IC50 values. Ligands selective for mu (mu) and kappa (kappa) opioid receptors were only effective in inhibiting [3H]naltrindole binding at micromolar concentrations. From these data, we conclude that [3H]naltrindole is a high affinity, selective radioligand for delta opioid receptors. PMID- 1313134 TI - Sigma (sigma) antagonist BMY 14802 prevents methamphetamine-induced sensitization. AB - We have demonstrated for the first time that the sigma antagonist BMY 14802 prevents the development of behavioral sensitization induced by repeated administration of methamphetamine. Rats received an intraperitoneal injection of 15 or 30 mg/kg BMY 14802 followed by 2 mg/kg methamphetamine 30 min later. Unlike dopamine antagonists, BMY 14802 did not induce major changes in the acute motor effects of 2 mg/kg methamphetamine. Repeated administration of methamphetamine induced progressive augmentation of stereotyped behaviors and resulted in behavioral sensitization. However, repeated administration of methamphetamine in combination with BMY 14802 at either dose produced no increase in the intensity of stereotypy when compared with the first treatment. After a 7-day abstinence period, a challenge test with methamphetamine alone revealed supersensitivity of methamphetamine-sensitized rats to subsequent methamphetamine, whereas rats pretreated with repeated methamphetamine in combination with BMY 14802 exhibited no difference in the intensity of stereotypy from rats pretreated with repeated saline. These results suggest that sigma receptors play a crucial role in the induction of methamphetamine-induced sensitization. PMID- 1313135 TI - Chronic morphine treatment increases the number, but decreases the affinity of [3H]-U69,593 binding sites in the rat heart. AB - In the present study, the effects of chronic morphine treatment on the binding properties of tritiated U69,593, a specific kappa-ligand, in the rat heart were determined. Adult rats were given morphine through osmotic pumps at a rate of 80 micrograms/hour supplemented by daily injection of morphine at increasing doses for 9 days. The increase in colonic temperature to morphine, used as an indicator of development of tolerance in the rat, was measured daily. It was shown that, on day 7 following morphine treatment, the rats developed tolerance to morphine as indicated by an attenuated hyperthermic response to morphine. The [3H]-U69,593 specific binding properties were determined by direct receptor binding assay. The binding sites increased gradually and reached a significantly higher level at day 10. Scatchard analysis showed that both Bmax and Kd increased at day 10 following morphine treatment, indicating an increase in number of sites and a reduction in affinity to the kappa-ligand. Acute morphine injection at a dose of 10 mg/kg did not cause any significant alteration of [3H]-U69,593 binding sites. Two days after withdrawal of morphine, the [3H]-U69,593 binding sites returned to the original level. The finding of the present study indicates that there is an up regulation of number, but a reduction in affinity of kappa-binding sites following chronic morphine treatment. PMID- 1313136 TI - An opioid growth factor regulates the replication of microorganisms. AB - An opioid growth factor (OGF), [Met5]-enkephalin, interacts with the zeta (zeta) opioid receptor to modulate development of eukaryotes. We have found that [Met5] enkephalin, an endogenous opioid peptide serves to inhibit the growth of S. aureus. This effect on growth involves cell proliferative events and is under tonic control, since potent opioid antagonists accelerate cell replication. Both the OGF and zeta opioid receptor were associated with these microorganisms. Other opioid receptors (mu, delta and kappa) were not detected. OGF also controlled the growth of other bacteria: P. aeruginosa and S. marcesans. These results indicate that OGF and its receptor, known to be important in the regulation of mammalian development, also function in the growth of simple unicellular organisms. We suggest that the endogenous opioid system related to growth originated billions of years ago. PMID- 1313137 TI - Gestational modulation of myometrial proteins in the timed-pregnant Sprague Dawley rat. AB - These studies sought to test the hypothesis that the expression of myometrial proteins is modulated as the onset of parturition approaches. Myometrial proteins from timed-pregnant rats were analyzed utilizing sodium dodecylsulfate polyacrylamide gel and 2-dimensional electrophoresis, and Western blot techniques. SDS-PAGE gels demonstrated increased expression of at least 10 protein bands from 17 to 200+ KD. 2-dimensional gels confirmed the presence of at least five groups of gestationally modulated proteins. Western blots for phosphoinositide-specific phospholipase C demonstrated significant modulation of the expression of three isozymes. These studies have confirmed differential expression of myometrial proteins near term in the timed-pregnant rat; some of which play an important role in intracellular signal transduction in response to hormones and pharmacologic agents. PMID- 1313139 TI - SecB-binding does not maintain the translocation-competent state of prePhoE. AB - The role of SecB protein in the export of the precursor of outer membrane protein PhoE and mutant forms of this precursor was studied in vitro. When synthesized in the absence of SecB, translocation-competent prePhoE was observed post translationally, but addition of SecB was required for efficient translocation into inner membrane vesicles. The translocation competency of in vitro synthesized prePhoE diminished with a similar half-life during incubations in the presence or absence of SecB. The loss of translocation competency of prePhoE, synthesized in the presence of SecB, was not due to dissociation of prePhoE-SecB complexes as could be demonstrated in co-immunoprecipitation experiments with anti-SecB serum. Apparently, SecB does not maintain the translocation-competent conformation of prePhoE, but is mainly required for efficient targeting of this precursor to the export apparatus. PMID- 1313138 TI - Mitochondrial DNA phylogeny of the Old-World monkey tribe Papionini. AB - The evolution of the Old World monkey tribe Papionini, composed of macaques, baboons, mandrills, drills, and mangabeys, was examined using mitochondrial DNA (mtDNA) sequence data on the cytochrome oxidase subunit II gene. When analyzed cladistically, these data support a baboon clade of savannah (Papio) plus gelada (Theropithecus) baboons, as well as a clade containing drill (Mandrillus) plus mangabey (Cerocebus) genera. This result stands in opposition to most morphological phylogenies, which break up the baboon clade by placing Papio and Mandrillus as sister taxa and Theropithecus as a more distantly related lineage. Analyses of COII gene sequences also suggest that the papionin ancestral stock divided into two lineages, one leading to macaques and the other to the purely African genera. From a molecular evolutionary perspective, the papionin COII gene sequences reveal a pattern of amino acid replacements concentrated in the regions spanning the mitochondrial membrane. PMID- 1313140 TI - Cloning, sequencing and deletion from the chromosome of the gene encoding subunit I of the aa3-type cytochrome c oxidase of Rhodobacter sphaeroides. AB - The ctaD gene encoding subunit I of the aa3-type cytochrome c oxidase from Rhodobacter sphaeroides has been cloned. The gene encodes a polypeptide of 565 residues which is highly homologous to the sequences of subunit I from other prokaryotic and eukaryotic sources, e.g. 51% identity with that from bovine, and 75% identity with that from Paracoccus denitrificans. The ctaD gene was deleted from the chromosome of R. sphaeroides, resulting in a strain that spectroscopically lacks cytochrome a. This strain maintains about 50% of the cytochrome c oxidase activity of the wild-type strain owing to the presence of an alternate o-type cytochrome c oxidase. The aa3-type oxidase was restored by complementing the chromosomal deletion with a plasmid-borne copy of the ctaD gene. This system is well suited for site-directed mutagenesis probing of the structure and function of cytochrome c oxidase. PMID- 1313141 TI - [Clinical evaluation of the measurement of hepatosplenic volume ratio by computed tomography]. AB - The liver and spleen volume ratio (S/L ratio) was estimated with X-ray computed tomography. Clinical usefulness of S/L ratio was evaluated by comparison with other liver functions (retention rate of ICG, total bilirubin, serum albumin and cholinesterase activity) in 42 hepatocellular carcinoma patients with liver cirrhosis. The correlation between S/L ratio and retention rate of ICG, total bilirubin, serum albumin or cholinesterase activity was good (r = 0.870, r = 0.719, r = -0.691, or r = -0.606, respectively p less than 0.001). Positive correlation was observed between S/L ratio and retention rate of ICG or total bilirubin. Negative correlation was observed between S/L ratio and serum albumin or cholinesterase activity. In conclusion, the measurement of S/L ratio on computed tomography was considered to be useful as an evaluation for the degree of severity in liver cirrhosis by considering both effective hepatic blood flow and portal hypertension. PMID- 1313142 TI - The promoter region of the Escherichia coli pepD gene: deletion analysis and control by phosphate concentration. AB - A series of deletions removing progressively larger parts of the 5' flanking region of the Escherichia coli pepD gene was constructed. After fusing the resulting promoter fragments to the chromosomal malPQ operon, their activities were determined by assaying for amylomaltase, the product of the malQ gene. Transcription from the pepD promoter region in exponentially growing cells was estimated to be about 5 times less efficient than transcription from the induced lac promoter. Approximately 115 bp preceding the translation start site of the pepD gene are important for regular promoter functioning, whereas the more distal sequences could be deleted without any significant effects. In bacterial cultures containing limiting amounts of inorganic phosphate, the rate of de novo synthesis of peptidase D, simultaneously with the derepression of alkaline phosphatase, increased about fivefold as a consequence of phosphate starvation. This regulation was shown to occur at the transcriptional level by the use of chromosomal pepD promoter-malPQ fusions. The inducibility by phosphate limitation was conserved in all of the deletion clones in which the pepD promoter region was still functional. As demonstrated by the use of phoB, R, and M mutants, the modulation of pepD expression is independent of the genetic system controlling the pho regulon. PMID- 1313143 TI - Fot1, a new family of fungal transposable elements. AB - We report here the discovery of a family of transposable elements, which we refer to as Fot1 elements, in the fungal plant pathogen Fusarium oxysporum. The first element was identified as an insertion in the gene encoding nitrate reductase. It is 1928 bp long, has 44 bp inverted terminal repeats, contains a large open reading frame and is flanked by a 2 bp (TA) target site duplication. This element shares significant structural similarities with a class of transposons that includes Tc1 from Caenorhabditis elegans and therefore represents a new class of transposable elements in fungi. PMID- 1313144 TI - The pogo transposable element family of Drosophila melanogaster. AB - A 190 bp insertion is associated with the white-eosin mutation in Drosophila melanogaster. This insertion is a member of a family of transposable elements, pogo elements, which is of the same class as the P and hobo elements of D. melanogaster. Strains typically have many copies of a 190 bp element, 10-15 elements 1.1-1.5 kb in size and several copies of a 2.1 kb element. The smaller elements all appear to be derived from the largest by single internal deletions so that all elements share terminal sequences. They either always insert at the dinucleotide TA and have perfect 21 bp terminal inverse repeats, or have 22 bp inverse repeats and produce no duplication upon insertion. Analysis by DNA blotting of their distribution and occupancy of insertion sites in different strains suggests that they may be less mobile than P or hobo. The DNA sequence of the largest element has two long open reading frames on one strand which are joined by splicing as indicated by cDNA analysis. RNAs of this strand are made, whose sizes are similar to the major size classes of elements. A protein predicted by the DNA sequence has significant homology with a human centrosomal associated protein, CENP-B. Homologous sequences were not detected in other Drosophila species, suggesting that this transposable element family may be restricted to D. melanogaster. PMID- 1313145 TI - Tissue-specific position effects on alcohol dehydrogenase expression in Drosophila melanogaster. AB - Twenty transformed lines have been isolated as a result of the germ line insertion of a 3.2 kb alcohol dehydrogenase (Adh) gene fragment into an Adh negative strain of Drosophila melanogaster by P element-mediated transformation. More than half of these lines exhibited abnormal ADH expression. The level of ADH expression ranges from zero in some lines to near normal levels in others, and the pattern of ADH expression in the larval gut is also abnormal in many of these lines. Each of the abnormal tissue-specific patterns is stable and characterized by the absence or reduction of ADH expression in certain tissues. High levels of ectopic expression were not observed. In two of these lines, the pattern of ADH staining is highly restricted: it is limited to the medial midgut in line MM-50, and to the gastric caecae and the proventriculus in line GC-1. In heterozygotes between these two lines ADH is expressed in both of these tissues. To test the hypothesis that this abnormal expression is due to position effects, inserts were mobilized to new locations. The mobilized inserts exhibited new patterns of tissue-specific expression associated with new cytological insert locations, showing that the abnormal expression in lines MM-50 and GC-1 is due to tissue specific position effects and not to mutations. The results are discussed in the context of chromatin structure as a possible cause of these position effects. PMID- 1313146 TI - Sensitivity to plating of Escherichia coli cells expressing the cryA gene from Bacillus thuringiensis var. israelensis. AB - The gene (cytA) coding for the 27 kDa polypeptide of the Bacillus thuringiensis var. israelensis mosquito larvicidal delta-endotoxin, was cloned into a plasmid containing the T7 bacteriophage promoter. The plasmid was used to transform an Escherichia coli strain containing the T7 RNA polymerase gene 1, under the control of lacP. Loss of colony-forming ability without substantial lysis, associated with immediate inhibition of DNA synthesis, was observed after induction of transformed cells. The cytA gene product may kill E. coli cells by disrupting their chromosome replicating apparatus. PMID- 1313147 TI - Extra sequences found at P element excision sites in Drosophila melanogaster. AB - We have previously established a transgenic Drosophila line with a highly transposable P element insertion. Using this strain we analyzed transposition and excision of the P element at the molecular level. We examined sequences flanking the new insertion sites and those of the remnants after excision. Our results on mobilization of the P element demonstrate that target-site duplication at the original insertion site does not play a role in forward excision and transposition. After P element excision an 8 bp target-site duplication and part of the 31 bp terminal inverted repeat (5-18 bp) remained in all the strains examined. Moreover, in 11 out of 28 strains, extra sequences were found between the two remaining inverted repeats. The double-strand gap repair model does not explain the origin of these extra sequences. The mechanism creating them may be similar to the hairpin model proposed for the transposon Tam in Antirrhinum majus. PMID- 1313149 TI - FBI investigating NIH leaks. PMID- 1313148 TI - Reconstitution of an episomal mouse aprt gene as a consequence of recombination. AB - When a functional murine adenine phosphoribosyltransferase (aprt) gene linked to bovine papilloma virus (BPV) DNA is transfected into Aprt- L cells, the cells are rendered Aprt+ and the aprt gene persists as an episome. Cotransfection with two BPV vectors, one containing the 5' half of the aprt gene and the other the 3' half of the gene, that share about 300 bp of common sequence in intron 2, produces Aprt+ cells with functional aprt as an episome. Southern blot analysis of low molecular weight DNA derived from Hirt extracts revealed the regeneration of a diagnostic SmaI fragment, consistent with establishment of an episome with functional aprt that was reconstituted as a consequence of recombination. To establish cells with an episomal target for recombination, BPV vectors containing a G418 resistance marker and either the 5' half or 3' half of aprt were transfected into Aprt- L cells. Stably transfected cells, selected by their growth in G418, were in turn transfected with DNA containing the other half of the aprt gene. Following selection of Aprt+ cells, Southern blot and polymerase chain reaction (PCR) analysis of low molecular weight DNA confirmed the presence of a complete episomal aprt gene. The region of DNA shared by the episomal aprt fragment and the transfected aprt half was sequenced after PCR amplification of the reconstituted, episomal gene and was found to be wild type. The region of overlap that serves as the substrate for recombination lies entirely within an intron and can, therefore, tolerate nucleotide substitutions and deletions. The absence of such errors in the sequences examined is consistent with recombination events that are not error prone. PMID- 1313150 TI - Change in fraud review proposed. PMID- 1313151 TI - New mammalian chloride channel identified by expression cloning. AB - Ion channels selectively permeable to chloride ions regulate cell functions as diverse as excitability and control of cell volume. Using expression cloning techniques, a complementary DNA from an epithelial cell line has been isolated, sequenced and its putative structure examined by site-directed mutagenesis. This cDNA, encoding a 235-amino-acid protein, gave rise to a chloride-selective outward current when expressed in Xenopus oocytes. The expressed, outwardly rectifying chloride current was calcium-insensitive and was blocked by nucleotides applied to the cell surface. Mutation of a putative nucleotide binding site resulted in loss of nucleotide block but incurred dependence on extracellular calcium concentration. The unusual sequence of this putative channel protein suggests a new class of ion channels not related to other previously cloned chloride channels. PMID- 1313152 TI - Glycosyl-phosphatidylinositol linkage as a mechanism for cell-surface expression of immunoglobulin D. AB - The B-cell antigen receptor of the IgM and IgD class is a multimeric complex consisting of the membrane-bound form of the immunoglobulin molecule and two other proteins, Ig-alpha and Ig-beta. The Ig-alpha and Ig-beta proteins form a disulphide-linked alpha/beta heterodimer and are encoded by the mb-1 (ref 9, 10) and B29 genes, respectively. Surface expression of the membrane-bound IgM molecule requires assembly with the alpha/beta heterodimer. The IgD molecule, however, can be expressed on the cell surface in an alpha/beta-dependent and independent form. We show here that in the alpha/beta-independent form the IgD molecule is anchored in the plasma membrane through a glycosyl phosphatidylinositol linker. In the presence of the alpha/beta heterodimer, most of the otherwise glycosyl-phosphatidylinositol-linked IgD molecule is expressed on the cell surface as transmembrane proteins. PMID- 1313154 TI - Guidelines revised by NNA practice cabinet. PMID- 1313153 TI - Cardioviral internal ribosomal entry site is functional in a genetically engineered dicistronic poliovirus. AB - High mutation rates have driven RNA viruses to shorten their genomes to the minimum possible size. Mammalian (+)-strand RNA viruses and retroviruses have responded by reducing the number of cis-acting regulatory elements, a constraint that has led to the emergence of the polyprotein. Poliovirus is a (+)-stranded picornavirus whose polyprotein, encoded by an open reading frame spanning most of the viral RNA, is processed by virus-encoded proteinases. Despite their genetic austerity, picornaviruses have retained long 5' untranslated regions, which harbour cis-acting elements that promote initiation of translation independently of the uncapped 5' end of the viral messenger RNA. These elements are termed 'internal ribosomal entry sites' and are formed from highly structured RNA segments of at least 400 nucleotides. How these elements function is not known, but special RNA-binding proteins may be involved. The ribosome or its 40S subunit probably binds at or near a YnXmAUG motif (where Y is a pyrimidine and X is a purine) at the 3' border of the internal ribosomal entry site, which either provides the initiating codon or enables the ribosome to translocate to one downstream (E.W. et al., submitted). Initiation from most eukaryotic messenger RNAs usually occurs by ribosomal recognition of the 5' and subsequent scanning to the AUG codon. Here we describe a genetic strategy for the dissection of polyproteins which proves that an internal ribosomal entry site element can initiate translation independently of the 5' end. PMID- 1313155 TI - Hepatitis C virus in chronic hemodialysis patients with non-A, non-B hepatitis. AB - Sixteen of 110 hemodialysis (HD) patients fulfilling criteria of non-A, non B hepatitis (NANBH), i.e. alanine aminotransferase (ALT) greater than 50 U/ml in the absence of both serologic markers for acute HBV and HAV infections and clinical evidence of another cause of hepatitis, were tested for the presence of antibodies against hepatitis C virus (anti-HCV) by enzyme immunoassay (Ortho, Diagnostics). All (100%) were anti-HCV-positive. There were 5 patients with a monophasic (M) rise pattern (1 or 2 ALT rises), and 11 cases demonstrated a polyphasic (P) rise elevation pattern (more than 2). The mean ALT value of the M group was 202.3 +/- 209 U/ml and that of the P group was 116.6 +/- 39.1 U/ml. The patients received a mean of 19.1 +/- 16.2 units of packed red cells during the follow-up period (69.9 months). Only 1 patient received no blood transfusion. Six patients had a past HBV infection and 3 became HIV-infected in the course of this study. The high rate of infection of hemodialysis patients with hepatitis C virus in our setting points to the need for improved control measures. PMID- 1313156 TI - The effect of benzodiazepines on the binding of [3H]SCH 23390 in vivo. AB - The effect of flunitrazepam upon the binding of [3H]SCH 23390 in vivo was investigated. Acute treatment with flunitrazepam decreased the binding of [3H]SCH 23390 in the striatum in a dose-dependent manner. The time course of radioactivity in the striatum, cerebral cortex and cerebellum in controls and flunitrazepam (1 mg/kg)-treated mice was measured after intravenous injection of [3H]SCH 23390. The binding kinetics were calculated, using the cerebellum as a reference region for the estimation of the amount of free ligand in the brain. Flunitrazepam significantly decreased the input rate constant to the receptor compartment and the dissociation rate constant in vivo. An in vivo displacement study, using carrier SCH 23390, also showed significant reduction in the dissociation rate constant of [3H]SCH 23390 in vivo. The drug Ro 15-1788 reversed the effect of flunitrazepam, suggesting that this reduction in binding of [3H]SCH 23390 was mediated by benzodiazepine receptors. To evaluate the relationship between the reduction in binding of [3H]SCH 23390 in vivo and in vivo occupancy of benzodiazepine receptors, in vivo occupancy of benzodiazepine receptors was measured using [3H]Ro 15-1788. A non-linear relationship was found between the reduction in dopamine D1 receptor binding in vivo and the occupancy of benzodiazepine receptors in vivo, indicating that benzodiazepines exerted the maximum change in dopamine receptor binding at a low fractional occupancy of receptors. PMID- 1313157 TI - Down-regulation of central receptors for thyrotropin-releasing hormone in kappa opiate agonist-induced abstinence in the rat. AB - The effect of U-50,488H, a selective kappa opiate agonist, on tolerance dependence and abstinence on the TRH receptors of the spinal cord and discrete regions of the brain of male Sprague-Dawley rats was determined. Rats were injected intraperitoneally twice daily with 25 mg/kg of U-50,488H for 4 days. Rats serving as controls were injected with the vehicle. On day 5, rats which were labeled as tolerant to U-50,488H were injected with U-50,488H (25 mg/kg) and sacrificed 1 hr later, whereas those labeled as abstinent were sacrificed without any injection. The above procedure has been previously shown to produce a high degree of tolerance to the analgesic and hypothermic effects of U-50,488H. The spinal cord and regions of the brain (hippocampus, cortex, midbrain, hypothalamus, corpus striatum, pons and medulla, and amygdala) were isolated for binding studies. The ligand [3H]MeTRH was used for TRH receptors. The binding constants, Bmax and Kd values, of [3H]MeTRH to bind to membranes prepared from various regions of the brain and spinal cord of rats tolerant-dependent on U 50,488H were unaffected. However, in rats abstinent to U-50,488H, the binding of [3H]MeTRH to membranes of the hypothalamus, and pons and medulla, was decreased. The decreased binding of [3H]MeTRH to hypothalamic membranes was due to changes in Bmax value, while in pons and medulla it was due to an increase in the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313158 TI - Effects of prolonged administration of milnacipran, a new antidepressant, on receptors and monoamine uptake in the brain of the rat. AB - Most antidepressants produce changes in monoamine receptors in brain after chronic administration in animals. The most commonly described alterations are a decreased density and function of beta-adrenergic receptors and have been postulated to be the mechanisms by which antidepressants exert their therapeutic effect. Milnacipran (previous name midalcipran) is a new, clinically-effective antidepressant, which inhibits the uptake of both serotonin and noradrenaline but has no affinity for any pre- or postsynaptic receptor studied. When given either orally at 7.5 mg/kg twice daily for 3 days, at 30 mg/kg once daily for 3 weeks, by osmotic mini-pump at 30 mg/kg/day for 27 days, or in drinking water at approximately 15 mg/kg/day for 6 weeks and after a washout period of 24 hr, milnacipran produced no down-regulation of beta-adrenoceptors. In addition, there were no alterations of alpha 1- or alpha 2-adrenoceptors, 5-HT1, 5-HT2 receptors or benzodiazepine binding sites. Moreover, uptake and accumulation of serotonin and noradrenaline were unmodified. In addition, the potency for milnacipran to inhibit monoamine uptake in vitro in the cortex was not altered in treated rats, compared to control animals. Thus, in spite of its action on both the uptake of serotonin and noradrenaline, milnacipran appears to be without long-term action on beta-adrenoceptors or the other receptors studied, suggesting that, at least for this antidepressant, these modifications are not essential for clinical activity. PMID- 1313159 TI - Prior chronic exposure to cocaine inhibits the serotonergic stimulation of ACTH and secretion of corticosterone. AB - The effect of long-term pretreatment with cocaine on serotonergic regulation of ACTH (adrenocorticotropic hormone; corticotropin) and secretion of corticosterone in rats was investigated. The following observations were made: (1) Pretreatment with cocaine had no significant effect on basal levels of ACTH and corticosterone in plasma. However, cocaine caused a reduction in the ability of the 5-HT (5 hydroxytryptamine, serotonin) releaser p-chloroamphetamine (PCA) to increase corticosterone in plasma, 42 hr after the last injection of cocaine. (2) Exposure to cocaine for 7 days was sufficient to produce a maximal inhibition of the PCA induced increase in ACTH in plasma. (3) The inhibitory effect of cocaine on PCA induced release of ACTH was more marked than on corticosterone. (4) Conversely, the dose-dependent stimulatory effect of two 5-HT1 agonists, RU 24969 (5-methoxy 3-(1,2,3,4-tetrahydro-4-pyridinyl)-1H-indole) and m-CPP (m chlorophenylpiperazine), on ACTH and corticosterone was not reduced by 7 days of exposure to cocaine. Taken together, these findings indicate that pretreatment with cocaine reduced the function of serotonergic nerve-terminals but not postsynaptic receptors, that stimulate ACTH and secretion of corticosterone. PMID- 1313160 TI - Peripheral cerebral aneurysm associated with a glioma. AB - This 42-year-old man with acute subarachnoid, intraventricular and parenchymal hemorrhage from an angiographically and surgically confirmed successfully clipped, right splenial artery aneurysm, subsequently manifested a grade 3 astrocytoma at the site of the aneurysm. Intracranial aneurysms are recognized in association with metastases from cardiac myxoma and choriocarcinoma, but are rarely seen with primary brain tumors. In patients with nontraumatic peripheral aneurysms it would seem prudent to biopsy the aneurysm and/or surrounding necrotic tissue at the time of surgical clipping. PMID- 1313161 TI - Selective intra-arterial chemotherapy with BCNU in recurrent malignant gliomas. AB - Study of intra-arterial BCNU in 12 patients with recurrent glioblastoma multiforme and 5 patients with recurrent anaplastic astrocytoma already treated by surgery and radiotherapy indicates that the risk of BCNU toxicity can be reduced by the use of relatively low doses (160-180 mg/m2) of BCNU, the use of dextrose as solvent, selective injections of BCNU, and fast "bolus" injections of drug. No certain toxic effects of BCNU were observed in the 17 patients treated this way. Anaplastic astrocytomas, particularly in young patients, seem to respond relatively well to this treatment. PMID- 1313162 TI - [Prognostic implications of the proliferation index (H3-TdR-labeling index) and ploidy in neuroectodermal tumors (astrocytomas and glioblastomas)]. AB - Kinetic cellular methods were used in 53 cases of various sizes of astrocytomas and glioblastomas to obtain reliable prognostic information. Kinetic analysis revealed a wide variation of proliferative activity, with a gradual increase of the mean value from the most differentiated astrocytomas to glioblastomas. DNA content was significantly correlated with the degree of histological differentiation. Chromosomic patterns, which were detected in a few cases, were generally aspecific. The sole recurrent alteration in the karyotype was a small metacentric marker. The comparison of results obtained with the follow-up of patients showed that the labeling index offers a more accurate estimate of the proliferative potential of individual tumours, and thus of the probability of survival, than histological diagnosis and the evaluation of other biological parameters such as ploidy and karyotype. PMID- 1313163 TI - [Chronic use of glucomannan in the dietary treatment of severe obesity]. AB - Two groups of 25 severely obese patients underwent 3 months of hypocaloric diet therapy either alone or associated with a glucomannan-based fibrous diet supplement (approx. 4 g/die in 3 doses). The comparative analysis of the results obtained in both groups showed that the diet + glucomannan group had a more significant weight loss in relation to the fatty mass alone, an overall improvement in lipid status and carbohydrate tolerance, and a greater adherence to the diet in the absence of any relevant side effects. Due to the marked ability to satiate patients and the positive metabolic effects, glucomannan diet supplements have been found to be particularly efficacious and well tolerated even in the long-term treatment of severe obesity. PMID- 1313164 TI - Delta 9-tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication. AB - Studies of the discriminative stimulus effects of delta 9-THC are reviewed. The results of generalization studies in rats trained to discriminate delta 9-THC from nondrug provide evidence for the pharmacological specificity of the delta 9 THC stimulus. Only cannabinoid analogs of delta 9-THC substitute fully for delta 9-THC. The ability of cannabinoids to produce delta 9-THC-like discriminative stimulus effects appears to predict delta 9-THC- or marihuana-like effects in humans. Of the 11 cannabinoids tested in rats and humans, the results with 9 are in complete concordance, and results with the remaining two are inconclusive. This concordance provides evidence for the validity of delta 9-THC discrimination in rats as an animal model of cannabis intoxication. A number of natural and synthetic cannabinoids have delta 9-THC-like discriminative stimulus effects. They represent a 5,600-fold range of relative potencies. Micromolar potency estimates and relative potencies to delta 9-THC for these compounds are provided. Correlations between these values and potencies for cellular actions of cannabinoids can be used to establish the neural substrates of cannabis intoxication. PMID- 1313165 TI - Enoxaparin prophylaxis for deep vein thrombosis in orthopaedic surgery. AB - Seventeen patients undergoing elective total hip or knee joint replacement were given enoxaparin prophylaxis against deep vein thrombosis. Four patients developed clinical evidence of deep vein thrombosis, confirmed by venography. Two patients developed disseminated intravascular coagulation. PMID- 1313166 TI - CDC drops plan to restrict healthcare professionals with HIV from working. PMID- 1313168 TI - Cyclic AMP-dependent phosphorylation modifies the gating properties of L-type Ca2+ channels in bovine adrenal chromaffin cells. AB - We investigated the effects of cAMP-dependent phosphorylation on the voltage- and time-dependent gating properties of Ca2+ channel currents recorded from bovine adrenal chromaffin cells under whole-cell voltage clamp. Extracellular perfusion with the membrane-permeant activator of cAMP-dependent protein kinase, 8-bromo(8 Br)-cAMP (1 mM), caused a 49%, 29%, and 21% increase in Ca2+ current (ICa) amplitudes evoked by voltage steps to 0, +10, and +20 mV respectively (mean values from eight cells, p less than or equal to 0.05). Analysis of voltage dependent steady-state activation (m infinity) curves revealed a 0.70 +/- 0.27 charge increase in the activation-gate valency (zm) following 8-Br-cAMP perfusion. Similar responses were observed when Ba2+ was the charge carrier, where zm was increased by 1.33 +/- 0.34 charges (n = 8). The membrane potential for half activation (V1/2) was also significantly shifted 6 mV more negative for IBa (mean, n = 8). The time course for IBa (and ICa) activation was well described by second-order m2 kinetics. The derived time constant for activation (tau m) was voltage-dependent, and the tau m/V relation shifted negatively after 8-Br-cAMP treatment. Ca2+ channel gating rates were derived from the tau m and m infinity 2 values according to a Hodgkin-Huxley type m2 activation process. The forward rate (alpha m) for channel activation was increased by 8-Br-cAMP at membrane potentials greater than or equal to 0 mV, and the backward rate (beta m) decreased at potentials less than or equal to + 10 mV. Time-dependent inactivation of ICa consisted of a slowly decaying component (tau h approximately 300 ms) and a "non-inactivating" steady-state component. The currents contributed by the two inactivation processes displayed different voltage dependences, the effects of 8-Br-cAMP being exclusively on the slowly inactivating L-type component. PMID- 1313167 TI - Differential short-term desensitization to vasopressin, isoproterenol, glucagon, parathyroid hormone and calcitonin in the thick ascending limb of rat kidney. AB - Short-term desensitization to hormone-induced cAMP accumulation was investigated in the medullary (MTAL) and the cortical (CTAL) thick ascending limbs of Henle's loop isolated by microdissection from the rat kidney. The following agonists were studied: vasopressin, glucagon and human calcitonin in the MTAL, and vasopressin, glucagon, human calcitonin, parathyroid hormone (PTH) and the beta-adrenergic agonist isoproterenol in the CTAL. Isolated tubules were preincubated in vitro for 60 min in the presence or absence of a maximal concentration of one of the five agonists (vasopressin 10 nM, glucagon 10 nM, calcitonin 100 nM, PTH 10 nM, isoproterenol 1 microM). Desensitization induced by each agent to its own action was then quantified by measuring the amount of cAMP accumulating in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine and the same agonist concentration as that used during preincubation. In the MTAL, as previously reported, preincubation with vasopressin led to a marked (80%-85%) desensitization to this hormone. A significant hormone self-induced desensitization of about 45% was also obtained with glucagon, but not with calcitonin. In the CTAL, the following order of potency to elicit desensitization was observed: vasopressin (80%) greater than isoproterenol (50%) greater than glucagon (30%) greater than PTH (20%, NS) greater than calcitonin (10%, NS). Thus, the magnitude of desensitization varied greatly from one hormone to another, but for a given hormone, was of roughly similar extent in both MTAL and CTAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313169 TI - Inhibition of L-type calcium channels by internal GTP [gamma S] in mouse pancreatic beta cells. AB - Pretreatment of pancreatic beta cells with pertussis toxin resulted in a 30% increase in peak whole-cell Ca2+ currents recorded in the absence of exogenous intracellular guanine nucleotides. Intracellular application of 90 microM GTP[gamma S], by liberation from a caged precursor, resulted in 40% reduction of the peak Ca2+ current irrespective of whether the current was carried by Ca2+ or Ba2+. Effects on the delayed outward K+ current were small and restricted to a transient Ca(2+)-dependent K+ current component. Inhibition by GTP[gamma S] of the Ca2+ current was not mimicked by standard GTP and could not be prevented either by pretreatment with pertussis toxin or by inclusion of GDP[beta S] or cyclic AMP in the intracellular medium. The inhibitory effect of GTP[gamma S] could be counteracted by a prepulse to a large depolarizing voltage. A similar effect of a depolarizing prepulse was observed in control cells with no exogenous guanine nucleotides. These observations indicate that inhibition of beta cell Ca2+ current by G protein activation results from direct interaction with the channel and does not involve second-messenger systems. Our findings also suggest that the beta cell Ca2+ current is subject to resting inhibition by G proteins. PMID- 1313170 TI - Proton transport mechanism in the cell membrane of Xenopus laevis oocytes. AB - Mechanisms of H+ transport across the plasma cell membrane of prophase-arrested oocytes of Xenopus laevis were investigated by testing the effect of ion substitutions and inhibitors on cytoplasmic pH (pHi), membrane potential (Vm) and membrane resistance (Rm). During superfusion with control solution of pH = 7.4, pHi was 7.49 +/- 0.12 (n = 15), Vm was -61.9 +/- 7.8 mV (n = 34) (cytoplasm negative), and Rm was 2.9 +/- 1.5 M omega (n = 19). These data confirm that H+ ions are not distributed at electrochemical equilibrium. By following pHi during recovery of the oocytes from an acid load (20 mmol/l NH4Cl) in the presence and absence of extracellular Na+ or amiloride (1 mmol/l), a Na/H exchanger was identified. On the basis of the known Na+ gradient across the cell membrane, this transporter could suffice to generate the observed H+ disequilibrium distribution. Utilizing blockers or ion-concentration-step experiments no evidence was obtained for an ATP-driven H+ pump or for passive acid/base transporters such as H+ conductances or Na+ (HCO3-)3 cotransport. The membrane depolarization observed in response to extracellular acidification appeared to result from a pH-dependent, Ba(2+)-inhibitable K+ conductance. PMID- 1313171 TI - High-resolution measurements of gap-junctional conductance during perfusion with anti-connexin antibodies in pairs of cultured mammalian cells. AB - Antibodies against the main proteins in hepatic gap junctions--connexin-26 and connexin-32--have been used in conjunction with high-resolution patch-clamp techniques to investigate whether a relation exists between connexin type and conductance of single gap-junctional channels. Two different cell lines, BRL cells, derived from rat liver, and FL cells a human amniotic cell line exhibited the same single-channel conductances in double whole-cell recordings, but reacted differently upon dialysis with antibodies. Preliminary results indicate that both cell lines express mainly connexin-43. Thus, in spite of the inhibitory action of anti-cx26 and anti-cx32 antibodies observed, the data question the reliability of these antibodies for the functional characterization of gap-junction proteins in electrophysiological experiments. PMID- 1313173 TI - Pharmacokinetic evaluation of drug interactions with anti-human immunotrophic virus (HIV) Drugs. III. 2',3'-Dideoxycytidine (ddC) and zidovudine in monkeys. AB - A pharmacokinetic evaluation of a potential drug interaction between zidovudine (AZT) and dideoxycytidine (ddC) was conducted in monkeys. Each of six animals received 20 mg/kg of AZT intragastrically in the absence and presence of an intravenous steady-state dosage regimen of ddC. The regimen was designed to produce steady-state ddC plasma concentration of 1.77 micrograms/ml for 30 min. Plasma and urine samples were analyzed for AZT, its major glucuronide metabolite, GAZT, and ddC by HPLC techniques. Pharmacokinetic parameters for AZT and GAZT were calculated by non-compartmental methods. The mean apparent clearance of AZT was 1.40 and 1.78 L/hr/kg in the absence and presence of ddC, respectively. The mean AUC for GAZT was 36.39 micrograms-hr/ml in the absence of ddC and 28.81 micrograms-hr/ml in the presence of ddC. No statistical differences were found in these and other pharmacokinetic parameters in the absence and presence of ddC. The absence of an effect on AZT's pharmacokinetics by ddC is attributed to the primary metabolic and renal elimination pathways for AZT and ddC, respectively. The results of this study provide a rational basis to design combined AZT-ddC treatment regimens in AIDS patients. PMID- 1313172 TI - Effects of serotonin and cAMP on calcium currents in different neurones of Helix pomatia. AB - Effects of application of serotonin (5-HT) and intracellular administration of cyclic adenosine monophosphate (cAMP) on voltage-gated calcium current (ICa) were studied in isolated, intracellularly perfused Helix pomatia neurones. Two types of the effects of 5-HT (1-10 microM) were observed in different neurones: reversible inhibition (by about 20%) or reversible potentiation (up to 50%) of the current amplitude. Some cells did not respond to 5-HT application. In cells with the potentiating effect of 5-HT, ICa could also be increased by intracellular introduction of cAMP (100 microM), but not the guanosine analogue, cGMP (50-100 microM). These effects were not additive and could be potentiated by theophylline (5 mM) and 3-isobutyl-1-methylxanthine (IBMX, 100-500 microM); they could be mimicked by forskolin (10-50 microM) and abolished by tolbutamide (1-5 mM) or protein kinase inhibitor (500 micrograms/ml), indicating that cAMP dependent phosphorylation mediates the potentiating action of 5-HT on ICa. In neurones showing inhibitory effect of 5-HT, neither cAMP nor forskolin increased ICa. Methiothepin (10-50 microM), a 5-HT1,2 receptor antagonist, irreversibly inhibited the potentiating effect of 5-HT, while antagonists of 5-HT2 receptors cyproheptadine (10-50 microM) or ketanserine (10-60 microM) and of 5-HT3 receptors ISC 205-930 (10-50 microM) or cocaine (5-25 microM) had no effect on ICa and its enhancement by 5-HT. It is suggested that in certain snail neurones the possibility of cAMP-dependent up-regulation of ICa correlates with the presence of 5-HT1-like receptors in the neuronal membrane. PMID- 1313174 TI - Pancreatic exocrine carcinoma producing adrenocorticotropic hormone. AB - A rare case of pancreatic exocrine carcinoma with an endocrine component secreting adrenocorticotropic hormone (ACTH) is reported and discussed in relation to other cases previously published. The patient initially presented with a severe form of diabetes, which was treated accordingly. Persistence of hyperglycemia, along with other metabolic alterations and marked hypokalemia, led to the suggestion of abnormal ACTH secretion. In this patient, however, a florid Cushing's syndrome was not observed. The patient also developed hematological alterations, mainly leukopenia and thrombocytopenia, whose origins were unclear. At autopsy, a poorly-defined mass was discovered between the body and tail of the pancreas. Standard histology showed a moderately-differentiated adenocarcinoma. Immunohistochemical analysis of the tumor specimen demonstrated the presence of some neoplastic cells immunoreactive for chromogranin A, neuron-specific enolase and ACTH. These findings are consistent with the existence of an endocrine component within the exocrine carcinoma with ACTH differentiation. PMID- 1313175 TI - CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure. AB - A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza virus hemagglutinin and of proposing a number of potential new ligands to this protein. PMID- 1313176 TI - Metal ion stabilization of the conformation of a recombinant 19-kDa catalytic fragment of human fibroblast collagenase. AB - A recombinant 19-kDa human fibroblast collagenase catalytic fragment modeled on a naturally occurring proteolytic product was purified from E. coli inclusion bodies. Following renaturation in the presence of zinc and calcium, the fragment demonstrated catalytic activity with the same primary sequence specificity against small synthetic substrates as the full-length collagenase. Unlike the parent enzyme, it rapidly cleaved casein and gelatin but not native type I collagen. Intrinsic fluorescence of the three tryptophan residues was used to monitor the conformational state of the enzyme, which underwent a 24-nm red shift in emission upon denaturation accompanied by quenching of the fluorescence and loss of catalytic activity. Low concentrations of denaturant unfolded the fragment while the full-length enzyme displayed a shallow extended denaturation curve. Calcium remarkably stabilized the 19-kDa fragment, zinc less so, while together they were synergistically stabilizing. Among divalent cations, calcium was the most effective stabilizer, EC50 approximately 60 microM, and similar amounts were required for substrate hydrolysis. Catalytic activity was more sensitive to denaturation than was tryptophan fluorescence. Least sensitive was the polypeptide backbone secondary structure assessed by CD. These observations suggest that the folding of the 19-kDa collagenase fragment is a multistep process stabilized by calcium. PMID- 1313177 TI - [Low-molecular weight heparin. Chemical and pharmacologic characteristics of a new substance group for postoperative thrombosis prevention]. PMID- 1313178 TI - 3H-norepinephrine release in caudal artery of spontaneously hypertensive and Wistar-Kyoto rats: effects of altered salt diets. AB - The potassium-induced release of 3H-norepinephrine (3H-NE) was examined in the rat caudal artery. A simple and reliable method was developed to examine stimulated neurotransmitter release from this highly innervated resistance vessel. The potassium-induced release of 3H-NE was dose- and calcium-dependent. Stimulated 3H-NE release was elevated in the spontaneously hypertensive (SHR) compared to age-matched Wistar-Kyoto (WKY) animals (p less than 0.05). However, in animals at 5-6 weeks of age, where the blood pressure was not different between the SHR and WKY, the stimulation-induced release of 3H-NE was also not significantly different. Low salt diets for 7 days significantly decreased the potassium-induced release of 3H-NE from both 10- to 11-week-old SHR and WKY animals. High salt diets did not significantly effect 3H-NE release, even though the high salt diets for 7 days significantly increased the blood pressure in the SHR. The results suggest that the caudal artery is a good model to study stimulation-induced transmitter release and that elevated 3H-NE release plays a role in the development of hypertension in the SHR. Low salt diets, which did not lower blood pressure, were shown to decrease 3H-NE release. High salt diets elevated the blood pressure in the SHR but had no significant effect on stimulated 3H-NE release. PMID- 1313179 TI - Failure of adrenocorticotrophic hormone to release serum amyloid A in cattle. AB - The objective of this study was to determine whether adrenocorticotrophic hormone plays a direct role in the secretion of serum amyloid A (SAA) in cattle. Seven lactating Holstein-Friesian cows were given either saline or 25 iu adrenocorticotrophic hormone (ACTH) intravenously at 09.00 in a two factor crossover design. Plasma cortisol concentrations had increased significantly by one hour after the injection of ACTH, whereas the SAA level had not increased by 24 hours after injection. It is concluded that in cattle adrenocorticotrophic hormone has no direct influence on the release of SAA by the hepatocyte. PMID- 1313180 TI - Detection of TNF alpha receptors on ovine leucocytes by flow cytofluorimetry. AB - Tumour necrosis factor receptor activity was detected on sheep leucocytes using flow cytofluorimetry and commercially available fluorescent human tumour necrosis factor. The density of receptors per cell and the proportion of cells expressing TNF receptor activity was found to be in the following rank order: monocytes greater than granulocytes greater than lymphocytes. PMID- 1313181 TI - Dietary fibre in the diet of the growing pig: effects on apparent digestibility and resultant implications for its use in reducing the incidence of oesophagogastric parakeratosis. AB - The effects on apparent digestibility of increasing dietary fibre concentrations in barley-based diets by substituting for barley either bran, oatmeal by-product, guar gum or pectin were studied using 72 pigs. Increasing substitutions of bran up to a maximum of 300 g kg-1 gave progressive decreases in apparent digestibility of dry matter, ether extract and gross energy fractions and in digestible and metabolisable energy contents, progressive increases in apparent digestibility of modified acid detergent fibre but had no consistent effect on either nitrogen or extract free of nitrogen fractions. Increasing substitution of oatmeal by-product up to the same maximum gave significant linear decreases in apparent digestibility of dry matter, extract free of nitrogen and gross energy, significant depressions in apparent digestibility of modified acid detergent fibre and significant increases in ether extract. Guar gum and pectin, both substituted to a maximum of 50 g kg-1 had no significant effects on apparent digestibility. The results are discussed in the context of the concentrations of dietary fibre needed to reduce the incidence of oesophagogastric parakeratosis. PMID- 1313182 TI - Effects of vagotomy on ventilatory responses to CO2 in alligators. AB - Reptiles increase ventilation during hypercapnia at a constant temperature. In this study, the contributions of vagal vs non-vagal receptors to CO2 ventilatory responses were investigated in 16 sedated Alligator mississippiensis (25 mg/kg pentobarbital; 3 days prior to data collection). Four animals served as controls to assess the effects of time and/or anesthetic drift on ventilation and blood gases; significant ventilatory drift was not detected during the observation period. The effects of bilateral vagotomy on CO2 ventilatory responses were determined during spontaneous breathing (n = 6) and unidirectional ventilation (UDV; n = 6) at two body temperatures (Tb = 30 and 20 degrees C). Resting PaCO2, minute ventilation (VI), tidal volume (VT) and breathing frequency (f) were elevated at 30 degrees C relative to 20 degrees C in spontaneously breathing alligators. Increasing inspired CO2 to 5% increased PaCO2, f, VT and VI at both levels of Tb. Ventilatory sensitivity to CO2 (S = delta VI/delta PaCO2) was higher at 30 degrees C with a temperature coefficient (Q10) of 2.3. Vagotomy increased PaCO2 and VT, decreased f and had no effect on VI at either Tb. After vagotomy, hypercapnia had no effects on ventilation. When CO2 feedback loops were opened by UDV at a high flow rate (greater than 2 L/min), Tb had no effects on ventilatory efforts at constant PCO2, but hypercapnia significantly increased f, VT and VI. S was variable with a Q10 of 2.1. After vagotomy, a significant CO2 ventilatory response remained during UDV, but S was unaffected by Tb (Q10 = 0.8). The results indicate that non-vagal chemoreceptors contribute to CO2 ventilatory responses in alligators, although their contribution following vagotomy is evident only during unidirectional ventilation. Although tentative, the data also suggest that CO2-sensitive vagal receptors may be necessary for the temperature dependency of S. PMID- 1313183 TI - Primary liver cancer and occupational exposure. AB - In a dynamic population-based case-referent study on primary liver cancer and occupational exposure, the work histories of 344 cases and 861 referents, derived from the follow-up of the whole Finnish population in 1976-1978 and 1981, were analyzed by industry, occupation, and agent. After adjustment for alcohol consumption, elevated odds ratios were found for the categories other agricultural workers (mainly milkmaids), clerical workers, persons exposed to welding fumes and those exposed to other inorganic dusts (mainly silica). One possible explanation for the excess among milkmaids was exposure to dust from cattle feed contaminated with aflatoxins. The excess among clerical workers was probably due to nonoccupational factors or chance because occupational exposure was generally rare. The excesses for welding fumes and inorganic dusts, although compatible with occupational etiology, contradict the results of many previous studies carried out among workers exposed to silica dust and welders. PMID- 1313184 TI - Coverage of the "Gallo case". PMID- 1313185 TI - Fruit fly learning research mushrooms. PMID- 1313186 TI - Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes. AB - Mitogen-activated protein (MAP) kinases are activated in response to a variety of extracellular stimuli by phosphorylation on tyrosine and threonine residues. Xp42 is a Xenopus laevis MAP kinase that is activated during oocyte maturation. Modified forms of Xp42 that lacked enzymatic activity or either of the phosphorylation sites were expressed in Xenopus oocytes. When meiotic maturation was induced with progesterone, each mutant Xp42 was phosphorylated, indicating that at least one kinase was activated that can phosphorylate Xp42 on tyrosine and threonine. Phosphorylation of one residue is not strictly dependent on phosphorylation of the other. PMID- 1313187 TI - Intercellular communication and cell-cell adhesion. AB - In developmental biology, binary cell-cell interactions often determine the fate of one or both cell partners. The two cells must adhere to one another to allow chemical signals to be transmitted in one or both directions across the regions of cell-cell contact. The molecular mechanisms of cell-cell adhesion and intercellular communication, even if they are mediated by different cell surface components, may be functionally integrated in several different ways. Studies of helper T cells with antigen-presenting B cells in culture have illuminated such binary interactions. The possible application of similar mechanisms to other binary developmental systems is briefly explored. PMID- 1313188 TI - Cloning of a second type of activin receptor and functional characterization in Xenopus embryos. AB - A complementary DNA coding for a second type of activin receptor (ActRIIB) has been cloned from Xenopus laevis that fulfills the structural criteria of a transmembrane protein serine kinase. Ectodermal explants from embryos injected with activin receptor RNA show increased sensitivity to activin, as measured by the induction of muscle actin RNA. In addition, injected embryos display developmental defects characterized by inappropriate formation of dorsal mesodermal tissue. These results demonstrate that this receptor is involved in signal transduction and are consistent with the proposed role of activin in the induction and patterning of mesoderm in Xenopus embryos. PMID- 1313189 TI - Tumor necrosis factor-alpha activates the sphingomyelin signal transduction pathway in a cell-free system. AB - The mechanism of tumor necrosis factor (TNF)-alpha signaling is unknown. TNF alpha signaling may involve sphingomyelin hydrolysis to ceramide by a sphingomyelinase and stimulation of a ceramide-activated protein kinase. In a cell-free system, TNF-alpha induced a rapid reduction in membrane sphingomyelin content and a quantitative elevation in ceramide concentrations. Ceramide activated protein kinase activity also increased. Kinase activation was mimicked by addition of sphingomyelinase but not by phospholipases A2, C, or D. Reconstitution of this cascade in a cell-free system demonstrates tight coupling to the receptor, suggesting this is a signal transduction pathway for TNF-alpha. PMID- 1313190 TI - Extragonadal germ cell tumors and unrecognized germ cell tumors. PMID- 1313191 TI - Toxicity of treatment of germ cell tumors. AB - Great progress has been made in the management of testicular cancer in the past 15 years, with the attainment of the expectation of cure for most patients. In all of the efforts to reduce the toxicity of treatment, one governing principle should be retained: we must not reduce the chance of successful treatment in our attempts to avoid toxicity. Continued progress will only be achieved by the meticulous implementation of carefully structured trials with appropriate follow up schedules. If future studies are effected in an unstructured and uncontrolled fashion, physicians could become the most common cause of death of patients with testicular cancer. PMID- 1313192 TI - The genetic and biologic aspects of treatment response and resistance in male germ cell cancer. PMID- 1313193 TI - Mechanisms of tumor necrosis factor action. AB - Tumor necrosis factor (TNF) is able to induce a great diversity of cellular responses via modulating the expression of a number of different genes. The multitude of TNF activities may be explained by both structural and functional heterogeneity in TNF receptors as well as by a diversification of postreceptor signal transduction pathways. Purification of TNF receptors has revealed two major, distinct binding proteins (TR60 and TR80). TR60 seems to be an essential component for TNF signaling; the functional role of TR80 remains to be elucidated. The pathway of postreceptor signal transduction involves phospholipase A2, a phosphatidylcholine-specific phospholipase C, protein kinase C, and other serine/threonine and tyrosine-specific protein kinases with as yet unknown function. At the receiving end of TNF signaling, induction of gene expression is mediated through activation of nuclear transcription factors, such as NFkB, AP-1, IRF-1, and NF-GMa. PMID- 1313194 TI - The effect of 6-nitro-1,3,8-trichlorodibenzofuran as a partial estrogen in the female rat uterus. AB - Administration of 6-nitro-1,3,8-trichlorodibenzofuran (6-NCDF) caused a dose- and time-dependent increase in uterine wet weight and cytosolic and nuclear estrogen receptor (ER) and progesterone receptor (PR) levels in immature female Sprague Dawley rats. These estrogenic effects persisted for up to 96 or 144 hr after initial administration of 6-NCDF and could be observed at a dose as low as 2 mumol/kg. In contrast, 6-NCDF (25 mumol/kg) did not increase rat uterine peroxidase activity or epidermal growth factor (EGF) receptor binding activity. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), which exhibits a broad spectrum of antiestrogenic effects in the female rat uterus, inhibited the 17 beta-estradiol induced increase in uterine wet weights, cytosolic and nuclear ER and PR levels, peroxidase activity, and EGF receptor binding activity. In contrast, 2,3,7,8-TCDD inhibited the uterotropic effects caused by 6-NCDF but did not affect the 6-NCDF induced uterine ER and PR levels. 6-NCDF is a weak inducer of hepatic microsomal ethoxyresorufin O-deethylase activity and competitively binds to the aryl hydrocarbon (Ah) receptor but not the PR or ER. Thus both 6-NCDF and 2,3,7,8 TCDD, two ligands which bind to the Ah receptor, exhibit both partial estrogenic and antiestrogenic properties and serve as useful models for delineating the complex biochemical interactions between the ER and Ah receptor signal transduction pathways. PMID- 1313195 TI - [Nerve sparing retroperitoneal lymphadenectomy with intraoperative electrostimulation in patients with nonseminomatous testicular tumors]. AB - Thirteen patients with nonseminomatous testicular germ cell tumours underwent nerve-sparing retroperitoneal lymphadenectomy (RLA) with prospective isolation and preservation of postganglionic sympathetic nerve fibres. In all ten patients with pathological stage I in whom a unilateral nerve-sparing RLA was performed, ejaculation was preserved. In two of three patients with pathological stage IIa who underwent a bilateral RLA with a nerve-sparing technique on one side, ejaculation was also preserved. In nine patients intraoperative electrostimulation of isolated sympathetic nerve fibres was performed employing Brindley's stimulation device. The result was an immediate and reproducible ejaculation in seven patients. Thus electrostimulation of sympathetic nerves may be a useful intraoperative test for the identification of the nerve fibres that need to be protected for ejaculation. Nerve-sparing RLA seems to be superior to modified (unilateral) RLA with regard to preservation of ejaculation. PMID- 1313196 TI - A simple and rapid technique to process formalin-fixed, paraffin-embedded tissues for the detection of viruses by the polymerase chain reaction. AB - The use of chelating resin in a simple, rapid and efficient pre-treatment protocol to process formalin-fixed, paraffin-embedded specimens for the polymerase chain reaction (PCR) is described and compared to other pre-treatment techniques. With this modified PCR protocol, a variety of human autopsy and biopsy specimens were investigated for presence of DNA of human papilomaviruses, cytomegalovirus or Epstein-Barr virus. These viruses were detected in a productive or non-/low-productive state. Amplimers generated ranged from 88 to 450 base pairs length. Under the specified technical conditions, a considerable range of DNA molecules can be amplified from paraffin-embedded material, some older than 10 years. PMID- 1313197 TI - Immunohistochemical localization of platelet-derived growth factor receptors in the porcine uterus during the oestrous cycle and pregnancy. AB - The distribution of alpha- and beta-type receptors for PDGF was studied immunohistochemically in the uterus of cycling and pregnant pigs with well documented hormonal status in order to determine a possible steroid hormone dependence of its expression. Peroxidase-antiperoxidase (PAP) labelling at light microscopical level was done with rabbit polyclonal antisera recognizing either both alpha- and beta-type receptors (PDGFR-1), or selectively beta-type (PDGFR 3). Immunoreactivity to the PDGF-receptors of alpha- and beta-type (PDGFR-1) was present in all endometrial samples examined, being located principally on subepithelial stromal and endothelial cells, the wall of endometrial blood vessels and in the fetal placenta (trophoblast and adjoining blood capillaries). In the myometrium, the major reactive cells were the non-vascular smooth muscle cells, and to some extent, also those of the tunica media of major uterine vessels. No dramatic variations in the intensity of the reaction were noticed during the oestrous cycle. A very intense immunoreactivity was present at early pregnancy and at term, i.e. under major oestrogenic influence. The immunoreactivity to the PDGF-receptor antiserum R-3 (against beta-type) was similarly localized as that showed for R-1 antiserum, while of a weaker intensity. The results indicate the presence of PDGF receptors (alpha- and beta type) in the endo- and myometrium of cycling and pregnant pigs, and that their expression seems to be accentuated under oestrogenic influence. PMID- 1313198 TI - Synovial sarcoma in a dog. AB - Synovial sarcoma is an uncommon malignant tumour of mesenchymal origin, occurring mainly in the vicinity of a joint. Subsequent invasion of the joint and adjacent bones may occur. Less frequently the tumour may be localized in soft tissues remote from joints. Synovial sarcoma usually affects male middle-aged dogs of large breeds. The rate of tumour growth can vary from very slow to very rapid. The tumour is usually poorly defined and infiltrates the deeper structures. Metastasis and recurrence are common. Wide-field surgical excision of the tumour or amputation of the affected limb are the most frequently used forms of treatment. In the present case the dog, a 7-year-old male Alsatian, had a slowly growing tumour in the vicinity of the hip joint, bilaterally. There was no involvement of the bones surrounding the tumour. Surgical resection was performed and one year later the dog was reported to be normal. PMID- 1313199 TI - [Protective effect of dextromethorphan on the ischemic retinal damage in rabbit]. AB - To investigate the effect of dextromethorphan (DEX), N-methyl-D-aspartate (NMDA) receptor antagonist, on the retinal ischemia, 0.4%DEX hydrobromide was intravenously given to rabbits before, during and after retinal ischemia. Retinal function was monitored by electroretinogram (ERG). Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg for 90 or 120 min. Amplitudes of ERG.b-waves recorded after the 90 min ischemia recovered to 72.5 +/- 9.0% in the DEX group and 38.5 +/- 8.5% in the control group which was given normal saline. The maximal recovery rates of b-wave amplitudes after the 120 min ischemia were 44.0 +/- 7.9% in the DEX group and 21.0 +/- 1.3% in the control group. The recovery rates of the b-wave amplitudes in DEX group were significantly higher than in the control group (p less than 0.01). It was found that the effective dose of DEX was 0.1-0.4%. PMID- 1313200 TI - On the mechanism of action of antiarrhythmic agents. AB - Cardiac arrhythmias arise from disturbances in the functioning of the specific ion channels that normally control excitation or from the functional expression of previously latent channels. Antiarrhythmic agents act by blocking the membrane sodium, potassium, and calcium channels, but no agent has exclusive action on a given type of channel. Arrhythmias resulting from reentry form the largest group of clinically significant arrhythmias. Most arrhythmias result from depressed sodium channel function. The local anesthetic class of sodium channel blockers (class I agents) acts by slowing conduction and converting regions of unidirectional block to bidirectional block. Class III agents act by prolonging the action potential duration. Because potassium currents are normally responsible for repolarization of the cardiac action potentials, these agents are generally assumed to be potassium channel blockers. Class IV antiarrhythmics- calcium channel blockers--are used when a group of reentrant arrhythmias arises in regions in which conduction is primarily sustained by increases in permeability to calcium ions. The mechanisms of action of antiarrhythmic agents are discussed with respect to the basic cellular mechanisms of cardiac arrhythmias. PMID- 1313201 TI - Mechanisms of pharmacologic intervention at the level of the calcium channel. AB - Calcium channels are large, complex membrane proteins that mediate transmembrane calcium currents. At least 2 kinds of calcium channels are found in heart muscle- the transient type and the long-lasting type. Calcium currents are modulated by diverse endogenous and exogenous factors including hormones, catecholamines, and calcium antagonists. Calcium antagonists act preferentially on vascular smooth muscle and have relatively less effect on the calcium channels of heart muscle. Compared with heart muscle, vascular smooth muscle is relatively depolarized, suggesting that vascular smooth muscle cells have predominantly the long-lasting type of calcium currents. The differential binding to different types of calcium channels underlies the clinical efficacy of the calcium antagonists. A drug such as bepridil, which acts preferentially on the coronary vasculature rather than on the peripheral vasculature, dilates the coronary vessels without depressing cardiac contraction, a putative clinical advantage. PMID- 1313202 TI - Phase II trial of combination chemotherapy and irradiation in non-small-cell lung cancer, Radiation Therapy Oncology Group 88-04. AB - Encouraging results of several clinical trials utilizing combination chemotherapy and irradiation in unresectable non-small-cell lung cancer have been reported. A recent report from a cooperative group study suggested that preirradiation vinblastine and cisplatin improved survival over irradiation alone. In an attempt to enhance the possible effectiveness of combination chemotherapy and irradiation, the Radiation Therapy Oncology Group embarked on a Phase II trial utilizing preirradiation vinblastine (5 mg/m2 weekly x 5) and cisplatin (100 mg/m2) on days 1 and 29 prior to irradiation and on days 50, 71, and 92 during irradiation. The irradiation began on day 50 and consisted of 6300 cGy in 7 weeks. Between May 20, 1988 and May 1, 1989, 30 patients were entered on study. Seventy-two percent of patients had Karnofsky status greater than 90, and 76% had weight loss less than 5%. Forty-eight percent of the patients were younger than 60 years of age. Forty-five percent of the patients had Stage IIIA disease. Eighty-three percent of the patients received at least four courses of vinblastine, and 59% received at least four courses of cisplatin. Seventy-eight percent of the patients received at least 95% of the prescribed irradiation. The major toxicity was hematologic, and there were two fatal complications in the study group. The preliminary survival figures are encouraging. This combination of chemotherapy and irradiation appears to be tolerable and may merit further investigation. PMID- 1313203 TI - Adjuvant chemotherapy in high-risk breast cancer patients with ten or more positive lymph nodes. PMID- 1313204 TI - Fibrous histiocytoma of the parotid gland. AB - The light microscopic, electron microscopic, and immunocytochemical characteristics of a case of a fibrous histiocytoma arising in the parotid gland is presented. This neoplasm is very rare in this site and must be distinguished from other spindle cell tumors of the parotid gland, particularly those of epithelial and myoepithelial origins. Histologic characteristics similar to those displayed by dermatofibromas and dermatofibrosarcoma protuberans help to differentiate this tumor from other spindle cell tumors. The absence of cytochemical epithelial markers and the electron microscopic demonstration of fibroblasts and histiocytes are useful in establishing the diagnosis. This tumor, which was confined completely to the parotid gland, appears to have arisen from mesenchymal elements within the gland. PMID- 1313205 TI - A rapid, specific assay for superoxide release from phagocytes in small volumes of whole blood. AB - A rapid, specific assay was developed to measure the release of superoxide anion from stimulated phagocytic cells in small volumes of whole blood. The assay is based on the chemiluminescence that results when lucigenin (bis-N-methyl acridinium nitrate) is reduced by superoxide. Heparinized whole blood, at volumes from 0.2 mL to a single drop from a 20-gauge needle, was mixed with lucigenin and either a soluble or particulate stimulus (phorbol myristate acetate or opsonized zymosan particles, respectively) in a standard volume of 1 mL. The chemiluminescence was measured at 3-minute intervals for a 30-minute period in a luminometer capable of automated operation. Characteristic plots of chemiluminescence versus time were obtained. This assay is rapid and simple, obviates the need to isolate leukocytes from whole blood, is specific for superoxide, can be performed with both soluble and particulate stimuli, and is sensitive enough to detect characteristic responses with as little as a single drop of blood. Patients with chronic granulomatous disease were readily identified using this assay. The ability to use very small blood volumes makes the assay suitable for use in prenatal diagnosis. The main disadvantage of this assay compared to the often-employed slide nitroblue tetrazolium test, with respect to testing for chronic granulomatous disease, is that carriers of x linked chronic granulomatous disease are not readily detected with this chemiluminescence assay, as they are with the nitroblue tetrazolium test. PMID- 1313206 TI - Clinical significance of serum and urinary neopterin levels in patients with various liver diseases. AB - Serum and urinary neopterin levels were measured by radioimmunoassay in 120 healthy controls, 16 asymptomatic HBsAg carriers, 12 patients with acute hepatitis, 13 with chronic inactive hepatitis, 35 with chronic active hepatitis, 46 with liver cirrhosis, 18 with hepatocellular carcinoma, and 6 with alcoholic liver disease. Serum and urinary neopterin levels were significantly higher in almost all patients than in normal subjects. Neopterin levels were highest in acute hepatitis and correlated with the results of liver function tests, but did not show this correlation in chronic liver disease. In chronic liver disease, the levels of serum neopterin in non-A non-B viral patients was significantly increased, compared with those in B viral and alcoholic patients. The rate of abnormal urinary neopterin levels in chronic liver disease was higher than the rate of abnormal serum neopterin levels, but no difference was observed between the rates of abnormal serum and urinary levels in acute hepatitis and asymptomatic HBsAg carriers. These results indicate that serum and urinary neopterin levels may be useful markers for cell-mediated immunity in liver disease, and that the immune system response in chronic liver disease may be different for different pathogens. PMID- 1313207 TI - DNA methylation patterns of the gamma delta beta-globin genes in human fetal and adult erythroid tissues. AB - An investigation of the correlation between the gamma----beta-globin switch and DNA methylation was carried out. The restriction patterns obtained with methylation-sensitive and -insensitive enzymes indicated hypomethylation in the promoter region of the gamma-globin genes in fetal liver DNA but high methylation of the same region in all other samples (except in the presence of an elevated erythroblast count or leukemia). All samples appeared to be partially hypomethylated at the 5' end of the delta-globin gene and hypomethylated at the 3' region of the beta-globin gene. Although consistent with a role for DNA methylation in globin gene regulation, the results also suggest that other factors besides methylation may be required for regulation of the level of expression, and switching of the globin genes. PMID- 1313208 TI - Time-weighted averages, peaks, and other indices of exposure in occupational epidemiology. AB - Dose surrogates commonly used in occupational epidemiology are exposure intensity, exposure duration, and cumulative exposure. The appropriateness of any of these measures as dose indicators depends on the nature of the induction process for the disease under consideration. Peak exposure intensity is often associated with acute health outcomes, whereas cumulative exposure is generally more relevant for diseases with long induction times, i.e., "chronic" diseases. However, there may be situations where peak exposure is etiologically relevant in chronic disease induction, such as might occur with nonlinear rates of damage during brief intervals of very high exposure. An approach is described for evaluating the effect of peak exposures in which peaks may be defined on a relative basis for each worker, or with respect to an absolute value, such as the permissible occupational exposure limit. The analytic strategy is illustrated with data from a case-control study of silicosis in relation to quantitative estimates of silica exposure. In this example, relative peak exposures and average non-peak exposures appear to be better predictors of silicosis risk than cumulative exposure. PMID- 1313209 TI - Partial gonadal dysgenesis in a patient with a marker Y chromosome. AB - We evaluated a patient with partial gonadal dysgenesis including a right dysgenetic testis and a left streak gonad with rudimentary fallopian tube and uterus. She had ambiguous external genitalia and was raised female. Although her height is normal (25th centile at age 12 years), she has some findings of Ullrich Turner syndrome. Her karyotype was reported to be 46,X,+marker; subsequent molecular investigations showed the marker to be the short arm of the Y chromosome. Genomic DNA, isolated from leukocytes of the patient and her father, was digested with a variety of restriction endonucleases and subjected to Southern blot analysis. A positive hybridization signal was obtained with probes for the short arm of the Y chromosome (pRsY0.55, SRY, ZFY, 47Z, pY-190, and YC-2) in DNA from the patient, indicating the presence of most if not all of the short arm, while long arm probes (HinfA and pY3.4) indicated that at least 75% of the long arm of the Y chromosome was missing. The gene responsible for testicular determination (TDF) is on the distal portion of the short arm of the Y chromosome; Yq has no known influence on sex determination. Hence, the deletion of the long arm of the Y chromosome cannot explain the gonadal dysgenesis in this patient. One explanation for the gonadal dysgenesis and Ullrich-Turner phenotype in the patient could be undetected 45,X/46,X,+marY mosaicism but no such mosaicism was observed in peripheral lymphocytes. Several investigators have suggested the presence of an "anti-Turner" gene near TDF. Hence it is possible that the clinical phenotype in our patient results from a Y chromosomal defect in sequences flanking TDF, which reduces the function of both TDF and the "anti Turner" genes. PMID- 1313210 TI - Blunting of clonidine-stimulated growth hormone release in mania. PMID- 1313211 TI - Effects of halothane on electrophysiologic properties and cyclic adenosine 3',5' monophosphate content in isolated guinea pig hearts. AB - We studied the effects of halothane on the electrophysiologic and biochemical properties of both Langendorff perfused hearts and single ventricular myocytes isolated from guinea pigs. Isometric contractions of left ventricles in perfused hearts, elicited by atrial pacing, decreased to 14% of control after exposure to 2% halothane-equilibrated perfusate. Subsequently the slow inward Ca2+ current (ICa) was recorded in isolated myocytes with a whole cell voltage clamp technique. ICa, recorded in response to 100-ms depolarizations from -40 mV to 0 mV, was decreased by 2% halothane to 28.4% of control. Halothane-induced ICa depression did not exhibit use dependency. To define a possible site at which halothane acts, we measured the cyclic adenosine 3',5'-monophosphate (cAMP) content of single ventricular myocytes using a radioimmunoassay. Two percent halothane decreased myocardial cAMP content to 68.9% of control. Further addition of dibutyryl cAMP (10(-3) mol/L) partially reversed the depressed contractility during 2% halothane administration in perfused hearts. In conclusion, the present study demonstrated that the decrease of myocardial cAMP by halothane was due to a direct action, at least partly, and not to other factors such as catecholamines, and suggested that the decreases in contractility and ICa were induced possibly through the decrease in cellular cAMP. PMID- 1313212 TI - Guidelines for preventing tuberculosis transmission in health care settings: what's new? PMID- 1313213 TI - Commentary from the APIC Guidelines Committee on the Centers for Disease Control "Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Settings, with Special Focus on HIV-related Issues". PMID- 1313214 TI - Surfactant replacement therapy improves pulmonary mechanics in end-stage influenza A pneumonia in mice. AB - Surfactant replacement therapy may be a promising approach for treatment of respiratory failure caused by viral pneumonia. This study in mice demonstrates that during the development of lethal influenza A pneumonia, thorax-lung compliance (Ctl/kg) and lung volume at 5 cm H2O PEEP (V5/kg) significantly decrease (28 and 54%, respectively), whereas lung water content significantly increases (25%). Surfactant replacement therapy during the end stage of pneumonia significantly increases Ctl/kg (31%) and V5/kg (21%). Instillation of the vehicle for surfactant in control animals does not significantly affect Ctl/kg (5% decrease), but it significantly decreases V5/kg (25% decrease). Further, a new method for postmortem measurement of lung volumes in small laboratory animals based on Archimedes' principle is presented. PMID- 1313215 TI - Detection of Epstein-Barr virus in lymphocytic interstitial pneumonia by in situ hybridization. AB - The involvement of Epstein-Barr virus (EBV) in the pathogenesis of lymphocytic interstitial pneumonia (LIP) was investigated using an in situ hybridization technique. Archival lung tissue samples from 14 patients (six men and eight women with a mean age of 58 +/- 3 yr) in whom a diagnosis of LIP had been previously established were retrospectively examined and compared with samples from 10 patients (six men and four women with a mean age of 58 +/- 3 yr) with idiopathic pulmonary fibrosis (IPF) who served as control subjects. In patients with LIP, the immunophenotype of the lymphocytic infiltrate was determined by using monoclonal antibodies to both pan-B-cell and pan-T-cell markers. In situ hybridization studies were performed by using the BamHI-W region of the EBV genome as a probe and a colorimetric detection method. The immunophenotyping studies showed that the interstitial infiltrate in LIP was primarily made up of B lymphocytes, particularly within the lymphoid aggregates, whereas T-lymphocytes were sparsely distributed along the alveolar septa. The in situ hybridization studies showed the presence of cells bearing the EBV genome in nine cases of LIP and in two cases of IPF (p less than 0.05, Fisher's exact test). In LIP, the EBV positive cells were observed in both enlarged and normal septa and occasionally within the lymphoid aggregates. We conclude that EBV may promote the proliferation of B-lymphocytes in a substantial number of patients with LIP. PMID- 1313216 TI - Controversies in the nonsurgical treatment of stage III non-small cell lung cancer. PMID- 1313217 TI - [Endocrine component of exocrine pancreatic tumors. Apropos of 2 cases]. AB - Two cases of pancreatic exocrine tumors with endocrine component are reported. The first case concerned a microcystic cystadenoma including an endocrine tumor identified by Grimelius staining and positive immunostaining for neurone specific enolase and the second a tubular adenocarcinoma including cells with positive immunostaining for glucagon and neurone specific enolase. The malignant nature of the endocrine component of both tumors which was certain for the first one and probable for the second whose endocrine component was distinct from the hyperplastic endocrine reaction observed at the periphery of the tumor, seems to support the hypothesis of exocrine and endocrine differentiation from a common precursor cell. The precise value of such a sub-group of pancreatic tumors with double component need to be clarified. PMID- 1313218 TI - [Anal ulcerations caused by cytomegaloviruses in patients with AIDS. Apropos of 6 cases]. PMID- 1313219 TI - A combination of human cytomegalovirus (HCMV)-specific murine monoclonal antibodies exhibits synergistic antiviral activity in vitro. AB - A combination of HCMV-specific monoclonal antibodies (MAbs) reactive with glycoproteins in gcI complexes which exhibit synergistic antiviral activity in vitro is described. MAbs directed against different structural and biological properties of HCMV have been selected to increase the antiviral activity against all possible strains, and to reduce the likelihood that resistant strains will emerge with prolonged exposure. Furthermore, in vitro analysis demonstrates that certain of the MAbs in the combination augment the virus-neutralizing activity of other component antibodies, thereby decreasing the amount of total antibody protein required to inhibit HCMV infection. Certain MAbs have been selected to inactivate extracellular virus during the early phase of HCMV infection, whereas others have been selected to prevent its spread once cells have been infected. These data suggest that a MAb cocktail may be useful for prophylaxis and treatment of patients at risk of life-threatening HCMV infections. PMID- 1313220 TI - Deletion of the herpes simplex virus type 1 ribonucleotide reductase gene alters virulence and latency in vivo. AB - The role of herpes simplex virus type 1 (HSV-1)-encoded ribonucleotide reductase (RR) has been investigated in mice and guinea pigs using a mutant from which 90% of the large subunit of the enzyme was deleted. The RR mutant was extremely impaired in its ability to induce external vaginal lesions or to cause death in mice following intracerebral, intraperitoneal, or intravaginal inoculation, or in guinea pigs following intraperitoneal or intravaginal inoculation. The RR mutant replicated poorly in the vagina of mice and guinea pigs when compared with the parental virus. Neither infectious nor latent virus was recovered from the trigeminal ganglia of mice or from the dorsal root ganglia of mice and guinea pigs after inoculation with the RR mutant. Using the polymerase chain reaction, RR mutant DNA was, nevertheless, detected in the dorsal root ganglia of guinea pigs. These studies suggest that HSV-1 RR is essential for virulence and may also play a role in the recovery of reactivatable latent virus from ganglia in both mice and guinea pigs. PMID- 1313221 TI - Evaluation of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil in a rabbit model of herpetic keratitis. AB - The nucleoside analog 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5- ethyluracil (FEAU) was tested in a rabbit model of acute herpetic keratitis and its effectiveness compared with that of acyclovir (ACV). FEAU or ACV was applied topically 3 times daily, beginning 3 days post-HSV-1 inoculation and continued for a period of 7 days. FEAU at a concentration of 1% (w/v) or 3% ACV resulted in significant lessening of the severity of corneal lesions, conjunctivitis, iritis, and corneal clouding at 24 to 48 h after beginning chemotherapy. No toxic reaction was observed in any rabbit eyes treated with either FEAU or ACV. The duration of virus shedding into tear film and colonization of the trigeminal ganglia, however, were not reduced by either FEAU or ACV treatment begun 3 days post-inoculation. Fifty percent effective dose (ED50) of FEAU determinations performed on isolates from tear film and on the virus inoculum in secondary rabbit kidney cultures yielded a range of 4.6-7 microM, with two in vitro resistant isolates having ED50S of greater than or equal to 1500 microM of FEAU. Fifty percent cell growth inhibition for FEAU was 3000 microM at 72 h. PMID- 1313222 TI - Ribavirin mitigates wart growth in rabbits at early stages of infection with cottontail rabbit papillomavirus. AB - The challenge to develop antiviral agents effective against DNA viruses such as human papillomavirus (HPV) has been dependent on finding an animal model which mimics the human forms of the disease. We have used an existing model system for the purpose of measuring the effect of antiviral drugs on the inhibition of growth of these lesions. This was based upon domestic rabbits which efficiently grow cutaneous papillomas (warts) when infected with cottontail rabbit papillomavirus (CRPV). One agent which had shown significant success in achieving these goals was ribavirin. Ribavirin was administered intradermally shortly prior to infection at multiple sites with CRPV. Following daily injections of this drug for eight weeks, we have shown a dose-dependent response which had markedly reduced the number of warts, the time of first appearance of warts and reduced the tumor mass as compared to placebo-treated control animals. At the highest dose of ribavirin tested, 30 mg/kg/day, compared to controls, the average reduction in the number of warts was 52%, the average time of first appearance of warts was 49% longer, and the average mass of the warts was reduced by 98%. No detectable antibodies to CRPV were observed in any of the animals. The only side effects which were observed was focal alopecia, and a decrease in body growth upon prolonged treatment, both of which were completely reversible. Pharmacokinetic studies established the metabolism of ribavirin over a 24-h period of time. Ribavirin administered beginning 12 or 30 days post-infection, while not reducing the number of warts, slightly retarded the growth of warts as determined by date of first appearance of warts and mass of warts. PMID- 1313223 TI - Influence of cow manure and composts on the effects of chlorfenvinphos on field crops. AB - Cauliflower crops were grown in several regions and seasons (spring and summer). Five days after planting, the plants were treated against the root fly by pouring onto soil around the plant stem an emulsion of chlorfenvinphos [2-chloro-1-(2,4 dichlorophenyl) ethenyl diethyl phosphate] in water. The fields were divided into plots. Onto each plot, one of the organic fertilizers, city refuse compost, mushroom cultivation compost, or cow manure was applied at the rate of 100 tons/ha, 1 or 3.5 months before the insecticide treatment. There were also control plots which were not treated with any of the organic fertilizers. During the first 50 days crop period which followed the insecticide treatment, the chlorfenvinphos soil concentrations were always greater in the organic fertilizer treated plots, than in the untreated ones (controls). The intensity of the organic fertilizers effect as to the increase of chlorfenvinphos soil persistence was in the following increasing order: city refuse compost less than cow manure less than mushroom cultivation compost. The organic fertilizer effects were greater when they had been soil-incorporated 3.5 months--instead of 1 month- before the chlorfenvinphos soil treatment. The increase of the insecticide soil concentrations--due to the organic fertilizers treatments--should increase the plant protection efficiency during the period of the first 50 days, during which time the young plants are the most sensitive to insects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313225 TI - Poxvirus infection in two crocodiles. PMID- 1313224 TI - DNA content in correlation with postsurgical stage in non-small cell lung cancer. AB - The relationship between DNA content, TNM stage, tumor size, grade, histology, and disease-free survival was assessed in a retrospective study of patients with non-small cell lung cancer who had undergone resection and complete mediastinal lymph node dissection. Flow cytometric analysis was performed on paraffin embedded tissue of 90 consecutive patients. The patients were analyzed both as a group and by individual stage. Median follow-up was 11 months (range, 1 to 35 months). Aneuploid tumors were not significantly different from diploid tumors with regard to pathologic TNM stage (p = 0.34), size (p = 0.5), grade (p = 0.5), or histology (p = 0.34). Disease-free survival of patients with aneuploid tumors was not significantly different than that of patients whose tumors had normal DNA content (p = 0.69). DNA content did not correlate with established prognostic factors in patients with non-small cell lung cancer who underwent resection and complete mediastinal lymph node dissection. PMID- 1313226 TI - Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes. AB - We have examined the effect of leukotriene B4 (LTB4), a potent lipid proinflammatory mediator, on the expression of the proto-oncogenes c-jun and c fos. In addition, we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation. LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner. The c jun mRNA, which is constitutively expressed in human peripheral-blood monocytes at relatively high levels, was also slightly augmented by LTB4, although to a much lower extent than c-fos. The kinetics of expression of the two genes were also slightly different, with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min. Both messages rapidly declined thereafter. Stability of the c-fos and c-jun mRNA was not affected by LTB4, as assessed after actinomycin D treatment. Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold. Resting monocytes contained nuclear factors binding to the AP-1 element, but stimulation of monocytes with LTB4 induced greater AP-1-binding activity of nuclear proteins. These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1-binding proto-oncogene products. PMID- 1313227 TI - Zone-specific inducibility of cytochrome P450 2B1/2 is retained in isolated perivenous hepatocytes. AB - The expression and induction of the cytochrome P450 2B1/2 isoenzyme is heterogeneous, exhibiting a regional pattern in the intact liver and a varied response to phenobarbital in isolated cultured hepatocytes. We report that P450 2B1/2 immunostaining of hepatocytes isolated from the perivenous liver region and cultured in the presence of phenobarbital is much stronger than that of cells identically treated but isolated from the periportal region. P450 2B1 mRNA, quantified by a sensitive and specific RNAase protection assay, is also preferentially induced in perivenous hepatocytes, demonstrating that the difference in induced expression is at the pretranslational level. Our results suggest that perivenous and periportal hepatocytes are differentially imprinted to retain regiospecific factors governing their inducibility after isolation. PMID- 1313228 TI - Molybdate and tungstate act like vanadate on glucose metabolism in isolated hepatocytes. AB - In rat hepatocytes, molybdate and tungstate inactivate glycogen synthase by a mechanism independent of Ca2+ and activate glycogen phosphorylase by a Ca(2+) dependent mechanism. On the other hand, both molybdate and tungstate increase fructose 2,6-bisphosphate levels and counteract the decrease in this metabolite induced by glucagon. These effectors do not directly modify 6-phosphofructo-2 kinase activity, even though they partially counteract the inactivation of this enzyme induced by glucagon. These effects are related to an increase on the glycolytic flux, as indicated by the increase in L-lactate and CO2 production and the decrease in glucose 6-phosphate levels in the presence of glucose. All these effects are similar to those previously reported for vanadate, although molybdate and tungstate are less effective than vanadate. These results could indicate that molybdate, tungstate and vanadate act on glucose metabolism in isolated hepatocytes by a similar mechanism of action. PMID- 1313229 TI - Aldosterone antagonists destabilize the mineralocorticosteroid receptor. AB - To elucidate the mechanism of action of aldosterone antagonists, we studied the interaction of spironolactone with the chick mineralocorticosteroid receptor (MR). Intestinal cytosol contains specific spironolactone-binding sites (Kd approximately 3 nM; max. no. of binding sites approximately 100 fmol/mg of protein) that have been identified as MRs by competition experiments with steroid ligands and with the monoclonal anti-idiotypic antibody H10E that interacts with aldosterone-binding domain of the MR. Binding studies indicate that aldosterone and spironolactone bind to the MR through a common site that encompasses the epitope recognized by H10E. At 4 degrees C, spironolactone dissociates much more rapidly from the cytosol 8-9 S form of MR (t1/2 38 min) than does aldosterone (t1/2 3240 min). A high dissociation rate was also observed for progesterone, a natural aldosterone antagonist (t1/2 84 min). The covalent linkage of the 90 kDa heat shock protein (hsp90) to the ligand-binding subunit of MR with dimethyl pimelimidate did not notably modify the rate of dissociation of spironolactone from the receptor (t1/2 96 min), excluding the possibility that the rapid dissociation rate of the antagonist was related to hsp90 release. The effects of aldosterone and the two anti-mineralocorticosteroids on the 8-9 S heterooligomeric structure of the MR differed strikingly. Using low-salt density gradient centrifugation analysis, aldosterone-labelled receptors were recovered as 8-9S complexes, whereas 4 S entities were detected after spironolactone and progesterone binding. This indicated that, under the experimental conditions used, aldosterone antagonists facilitate hsp90 release and thus do not stabilize the non-DNA-binding 8-9S form of MR. We propose that the combination of rapid dissociation of the ligand and a weakened hsp90-receptor interaction is involved in the anti-mineralococorticosteroid activity of aldosterone antagonists. PMID- 1313230 TI - Calcium-sensitivity of inositol 1,4,5-trisphosphate metabolism in exocrine cells from the avian salt gland. AB - The generation of inositol phosphates upon muscarinic-receptor activation was studied in [3H]inositol-loaded exocrine cells from the nasal salt glands of the duck Anas platyrhynchos, and the metabolism of different inositol phosphates in vitro was studied in tissue homogenates, with particular reference to the possible interaction of changes in intracellular [Ca2+] ([Ca2+]i) with the metabolic processes. In intact cells, there was a rapid (within 15 s) generation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4, followed by an accumulation of their breakdown products, Ins(1,3,4)P3 and inositol bis- and monophosphates. Ca(2+) sensitivity of the Ins(1,4,5)P3 3-kinase was demonstrated in tissue homogenates, with the rate of phosphorylation increasing 2-fold at free Ca2+ concentrations greater than 1 microM. However, addition of calmodulin or the presence of the calmodulin inhibitor W-7 (up to 100 microM) had no effect. 3-Kinase activity increased proportionally with the initial Ins(1,4,5)P3 concentration up to 1 microM, but a 10-fold higher substrate concentration produced only a doubling in the phosphorylation rate. Ins(1,3,4,5)P4 was dephosphorylated to Ins(1,3,4)P3, which accumulated in the homogenate assays as well as in intact cells. Depending on its concentration, Ins(1,3,4)P3 was phosphorylated [in part to Ins(1,3,4,6)P4] or dephosphorylated. To investigate the Ca(2+)-sensitivity of the 3-kinase in intact cells, excess quin2 was used to buffer the receptor-mediated transient changes in [Ca2+]i in [3H]inositol-loaded cells. These experiments revealed that increasing [Ca2+]i from less than 100 to approx. 400 nM (i.e. within the physiological range) has no effect on the partitioning of Ins(1,4,5)P3 metabolism (phosphorylation versus dephosphorylation) and on the accumulation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4. This indicates that activation of the 3-kinase by physiologically relevant Ca2+ concentrations may not play a major role in the generation of Ins(1,3,4,5)P4 signals upon receptor activation in these cells. The latter are mainly achieved by the receptor-mediated increase in Ins(1,4,5)P3 in the cell and its phosphorylation by the 3-kinase in a substrate-concentration dependent manner. PMID- 1313231 TI - Cyclic AMP stimulates the synthesis and function of the low-density lipoprotein receptor in human vascular smooth-muscle cells and fibroblasts. AB - 1. Cyclic AMP-elevating agents stimulate low-density lipoprotein (LDL) receptor activity in human vascular smooth-muscle cells by increasing the rate of receptor protein synthesis. The stimulation is not secondary to the decrease in the regulatory pool of free cholesterol, since it is unaffected, or even enhanced, by inhibition of cholesterol synthesis and esterification, or inhibition of the conversion of cholesterol into its repressor metabolites. The cyclic AMP-mediated up-regulation of the receptor is maintained at low concentrations of inhibitory sterols, but is eventually over-ridden at high concentrations of these sterols. 2. Cyclic AMP-elevating agents also stimulate the hydrolysis of lysosomal cholesterol esters, thus increasing the cellular cholesterol pool and repressing the expression of the LDL receptor. This cholesterol-mediated repressive effect of cyclic AMP can be prevented by chloroquine, which inhibits lysosomal actions, or by ketoconazole, which inhibits conversion of free cholesterol into its repressor metabolite. Thus the cyclic AMP stimulation of the LDL receptor can be masked by the rapid mobilization of free cholesterol from existing cholesterol esters within cultured cells. 3. We have observed that elevated cyclic AMP concentrations will up-regulate the LDL receptor in cholesterol-depleted human vascular smooth-muscle cells, skin fibroblasts and foetal-lung fibroblasts. We propose that our results are evidence for a cyclic AMP-stimulated, sterol independent, control of LDL-receptor synthesis which is of widespread occurrence in human cells. PMID- 1313232 TI - Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives. AB - Four naturally occurring flavones (baicalein, quercetin, quercetagetin and myricetin) and two novel catechins [(-)-epicatechin gallate and (-) epigallocatechin gallate, from the tea plant Camellia sinensis], which are known inhibitors of reverse transcriptase, were shown to induce mammalian topoisomerase II-dependent DNA-cleavage in vitro. The flavones differed from the catechins in causing unwinding of duplex DNA, but both classes of compound induced enzymic DNA breakage at the same sites on DNA. Moreover, the cleavage specificity was the same as that for the known intercalator 4'-(acridin-9-ylamino)methanesulphon-m anisidide, suggesting that these agents trap the same cleavable complex. Analysis of some 30 flavonoid compounds allowed elucidation of the structure-function relationships for topoisomerase II-mediated DNA cleavage. For flavonoid inhibitors an unsaturated double bond between positions 2 and 3 of the pyrone ring and hydroxy groups at the 5, 7, 3' and 4' positions favoured efficient cleavage. Hydroxy substitutions could be tolerated at the 3, 6 and 5' positions. Indeed, the absence of substituents at the 3', 4' and 5' positions could be compensated by a hydroxy group at position 6 (baicalein). Similar requirements have been reported for flavonoid inhibitors of protein kinase C that act competitively with ATP, suggesting interaction with a conserved protein feature. Formation of the cleavable complex is a cytotoxic lesion that may contribute to the growth-inhibitory properties of flavones observed for three human tumour cell lines. These results are discussed in regard to the selectivity of antiviral agents. PMID- 1313233 TI - Regulation of inositol 1,4,5-trisphosphate metabolism by guanine nucleotides in membranes of cultured newborn rat cardiomyocytes. AB - Membranes of cultured newborn rat cardiomyocytes contain enzymatic activities that regulate the formation and the breakdown of inositol 1,4,5-trisphosphate (1,4,5-IP3). GTP gamma S increased the rate of exogenous [3H]phosphatidyl 4,5 bisphosphate ([3H]PIP2) hydrolysis (EC50: 40 microM). This effect was dependent on the presence of deoxycholate and maximal at 2 mM deoxycholate. GTP gamma S increased the efficacy of phospholipase C (PLC) (by 2.3-fold), but did not alter the apparent affinity of the enzyme for PIP2. Other nucleotides, GDP beta S and ATP gamma S, and pyrophosphate also stimulated PIP2 hydrolysis, while AlF4- was ineffective. The effect of GTP gamma S was not inhibited by GDP beta S. The agonists norepinephrine and thrombin, which by themselves had no effect, did not potentiate the response to GTP gamma S. In contrast, 1,4,5-IP3 hydrolysis was decreased by GTP gamma S (EC50: 100 microM) as well as by other nucleotides and by pyrophosphate, but not by AlF4-. GDP beta S did not antagonize the GTP gamma S induced inhibition of IP3 hydrolysis. These results suggest that GTP can stimulate the hydrolysis of exogenous PIP2 by an action on membrane-bound PLC at a site beyond the G protein activating PLC and inhibit the hydrolysis of 1,4,5 IP3 by a mechanism common to all nucleotides. Thus, GTP can regulate 1,4,5-IP3 metabolism by stimulating its formation and inhibiting its breakdown. PMID- 1313234 TI - Effects of the modulating agent WR2721 and its main metabolites on the formation and stability of cisplatin-DNA adducts in vitro in comparison to the effects of thiosulphate and diethyldithiocarbamate. AB - The influence of the modulating agent WR2721, its active thiol-metabolite WR1065 and the symmetrical disulphide WR33278 on the in vitro formation and stability of cis-diamminedichloroplatinum(II) (cisplatin, CDDP)-DNA adducts was investigated and compared with the effects of the highly nucleophilic modulating agents diethyldithiocarbamate (DDTC) and thiosulphate (TS). Salmon sperm DNA (0.5 mg/mL) was incubated with 25 micrograms/mL (83 microM) cisplatin for 1 hr in 50 mM phosphate buffer, pH 7.2 at 37 degrees in the absence or presence of modulating agent. DDTC and TS were potent inhibitors of the platination of the DNA (95 and 89%, respectively, with 4.2 mM of modulating agent). The WR-compounds were also remarkably active in the inhibition of DNA platination. Prevention of adduct formation in the presence of 4.2 mM WR-compound decreased in the order WR1065 (74%) greater than WR33278 (63%) greater than WR2721 (51%). The prevention of CDDP-DNA adduct formation by WR1065 was strongly concentration-dependent up to 4.2 mM but at higher concentrations this protection hardly increased at all. In the presence of the modulating agents, increased levels of CDDP monofunctionally bound to a guanine residue were observed with a simultaneous decrease in the relative abundance of bifunctional adducts. All modulators were also able to reverse part of the CDDP-DNA adducts formed. After a 2-hr incubation of already platinated salmon sperm DNA with 4.2 mM of modulating agent, the removal of Pt from DNA amounted to about 43% with DDTC, 28% with WR1065 and 13-14% with TS, WR2721 and WR33278. Even CDDP bifunctionally bound to two adjacent guanines in the same DNA strand, which is considered to be a very stable adduct, was partly reversed. Our observations suggest that WR2721, especially when administered prior to or concomitantly with CDDP, can be expected to protect those tissues from CDDP-induced damage to DNA that are able to efficiently dephosphorylate WR2721 followed by uptake of the thiol metabolite WR1065. This stresses the importance of a selective formation and uptake of WR1065 by non-tumour tissues for the successful use of WR2721 as a protective agent in combination with platinum-based cancer chemotherapy. PMID- 1313235 TI - Cyclosporine A inhibits ATP net uptake of rat kidney mitochondria. AB - The adenine nucleotide content of mitochondria varies at several physiological and pathological situations. Both net transport and intramitochondrial catabolism of adenine nucleotides has been suggested to be responsible for these changes. Here, the influence of cyclosporine A on the ATP net uptake of isolated rat kidney mitochondria was examined. The ATP net uptake of mitochondria depleted of matrix adenine nucleotides by pyrophosphate treatment was inhibited by cyclosporine A showing a I50 value of about 4 nmol/mg mitochondrial protein. Because intramitochondrial adenine nucleotide content is important for several mitochondrial functions such as oxidative phosphorylation, Ca2+ homoeostasis and mitochondrial biogenesis, it is concluded that the inhibition of adenine nucleotide net transport and a decrease of adenine nucleotide content may be involved in the immunosuppressive and nephrotoxic effects of cyclosporine A. PMID- 1313236 TI - Differential susceptibility of dihydroorotate dehydrogenase/oxidase to Brequinar Sodium (NSC 368 390) in vitro. AB - To verify the assumption of a specific and potent drug action on de novo pyrimidine biosynthesis, isolated dihydroorotate dehydrogenase (DHO-DH) (EC 1.3.3.1) was exposed to Brequinar Sodium (6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4 yl)-3-methyl-4-quinoline carboxylic acid sodium salt, NSC 368 390) (Brequinar). The membrane-bound DHO-DH was purified to apparent homogeneity (25,000-fold) from rat liver mitochondria in six steps via detergent extraction and subsequent chromatography using the dye ligand Matrex Gel Orange A. Using molecular mechanistic studies (MM2) this ligand was found to mimic closely the stereochemical conformation of Brequinar. SDS-PAGE revealed two protein bands for the purified enzyme with apparent molecular masses of 58 (major) and 68 kDa (minor). In vitro, two modes of action of the DHO-DH are possible: (i) acting as a dehydrogenase in the presence of ubiquinone as proximal electron acceptor and (ii) direct reaction with oxygen as oxidase. A novel assay for the measurement of the oxidase activity was adapted using leuco-dichlorofluorescein-diacetate. Inhibition experiments revealed a striking difference in the susceptibility of DHO-dehydrogenase/oxidase to Brequinar: apparent Ki = 6.09 +/- 0.05 (SD) nM (DHO; ubiquinone n = 10), but Ki = 3.10 +/- 0.09 (SD) mM (DHO; O2). Analyses of initial velocity experiments showed non-competitive inhibition of Brequinar with respect to the substrate dihydroorotic acid in both assays (dehydrogenase and oxidase). The inhibitory effect of the latter was compared to that of the competitive inhibitor 5-aza-dihydroorotate (apparent Ki = 15 +/- 0.25 (SD) microM). The present kinetic data on the action of the purified rodent DHO-DH with Brequinar and computer-aided analyses provide a better insight into the drug-enzyme interaction. PMID- 1313237 TI - Nitrofurantoin-induced pulmonary toxicity. In vivo evidence for oxidative stress mediated mechanisms. AB - The present study was carried out to examine whether nitrofurantoin-induced pulmonary toxicity in normal rats was mediated via oxidant stress mechanisms. The relative importance of the cellular antioxidant enzymes in nitrofurantoin toxicity was also assessed. For this, the pulmonary toxicity induced by nitrofurantoin in rats was evaluated at various time intervals after a single subcutaneous injection. Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity. A transient decrease in GSH concentrations with a concurrent increase in GSSG concentrations as well as an increase in lipid peroxidation levels (measured by the formation of diene conjugates and thiobarbituric acid reactants) were also evident in lungs of nitrofurantoin treated rats. In addition, nitrofurantoin did not alter the pulmonary superoxide dismutase and glutathione peroxidase activities, but it did produce transient decreases in catalase and glutathione reductase activities. These data indicate that impairment of the ability of the lung to detoxify reactive oxygen species may play an important role in the development of nitrofurantoin-induced pulmonary toxicity. The results of the present study suggest that nitrofurantoin can damage the lungs of rats, probably through oxidative stress-mediated mechanisms. Also, our data have provided in vivo evidence for substantiating lipid peroxidation as a possible cause of lung damage. PMID- 1313238 TI - [Virucidal effectiveness of some commercial products for chemothermal disinfection methods for temperature resistant viruses and bacteriophages- evaluation of a test model]. AB - In the laboratory assay of chemothermal virus disinfection procedures a test system is required which allows to differentiate between the physical effects of the temperature and the chemical effects by the disinfectant used. From the four test viruses recommended by the German Association for the Control of Virus Diseases (Deutsche Vereinigung zur Bekampfung der Viruskrankheiten) only SV 40 tumor virus showed a sufficient thermal stability at 55 degrees C to take it in consideration as test virus for chemothermal disinfection procedures. Bacteriophage Phi x 174 and lactococci phages P001, P008 and P109 are suggested for the evaluation of chemothermal disinfection procedures in food processing industries because of their thermal stability at 55 degrees C, for short exposition times even at 60 degrees C. For procedures which work at 60 degrees C, e.g. laundry disinfection, especially bovine parvovirus can be recommended as test virus. In case of a binary product consisting of two different compounds for mechanically cleaning and disinfection of surgical instruments we were able to evaluate the virucidal effectivity at 55 degrees C for both parts separately. Generally our results showed that products with insufficient virucidal activity against naked viruses even at 60 degrees C may not be assumed as sure virucidal disinfectants. PMID- 1313239 TI - Is the inhibition of protein phosphatase 1 and 2A activities a general mechanism of tumor promotion in human cancer development? PMID- 1313240 TI - Pairings of a drug or place conditioned stimulus with lithium chloride produce conditioned sickness, not antisickness. AB - In different experiments, pairings of a drug (pentobarbital or morphine) or place as the conditioned stimulus (CS) with lithium-induced sickness as the unconditioned stimulus (US) were given to rats to produce Pavlovian conditioning. Control rats received unpaired exposures. In the test, each rat was exposed to the CS, injected with lithium, and then offered food. If such pairings produce conditioning of antisickness (i.e., a compensatory response that opposes lithium sickness), then the experimental rats should eat more than the controls. The reverse occurred. Thus, pairings of a drug or place CS with a lithium US resulted in conditioned sickness rather than antisickness. PMID- 1313241 TI - Taste avoidance, but not aversion, learning in rats lacking gustatory cortex. AB - Control rats rapidly learned to avoid drinking either a sucrose solution (Experiment 1) or a NaCl solution (Experiment 2) when the taste was paired with illness. These rats also produced aversive reactivity to each of these solutions in a taste reactivity test. Rats that lacked gustatory cortex (GC) learned to avoid drinking sucrose and NaCl, albeit at a slower rate than control rats. GC rats failed to display aversive reactivity to these tastes. The GC rats did show normal aversive reactivity to a strong quinine HCl solution during additional tests. It is suggested that the avoidance developed by GC rats did not entail a palatability shift of the conditional stimulus as it did in control rats. This altered learning strategy may account for the consistent learning deficits found in GC rats trained to avoid tastes. PMID- 1313242 TI - Parabrachial gustatory lesions impair taste aversion learning in rats. AB - Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit. PMID- 1313243 TI - Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: comparison with novelty and locomotion. AB - Extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were examined concurrently, using in vivo microdialysis, in the nucleus accumbens and dorsal striatum of sexually active male rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually receptive female, and copulation. DA increased significantly in the nucleus accumbens when the males were presented with a sexually receptive female behind a screen and increased further during copulation. Although DA also increased significantly in the dorsal striatum during copulation, the magnitude of the effect was significantly lower than that observed in the nucleus accumbens. In contrast, forced locomotion on a rotating drum, exposure to a novel chamber, and exposure to sex odors did not increase DA significantly in either region, although both DOPAC and HVA increased significantly in both regions during the locomotion test. These results indicate that novelty or locomotor activity alone cannot account for the increased extracellular DA concentrations observed in the nucleus accumbens of male rats during the presentation of a sexually receptive female behind a screen, nor can they account for the increased DA concentrations observed in both the nucleus accumbens and dorsal striatum of male rats during copulation. The preferential increase in DA transmission in the nucleus accumbens, compared with that in the striatum, suggests that anticipatory and consummatory aspects of sexual activity may belong to a class of naturally occurring events with reward values that are mediated by DA release in the nucleus accumbens. PMID- 1313244 TI - Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. AB - Receptors for mineralocorticoids (MRs) and glucocorticoids (GRs) display a high concentration and distinct distribution in the hippocampus. The effects of corticosteroids on behavior mediated by central MRs and GRs were assessed in rats. Spatial navigation is considered to be a sensitive measure for hippocampal functioning. Removal of circulating corticosteroids (via adrenalectomy) impaired spatial learning. In intact rats, blockade of central MRs and GRs by intracerebroventricular injection of selective MR and GR antagonists influenced different aspects of spatial learning. The analysis of the behavioral pattern revealed that treatment with the MR antagonist altered search-escape strategies in the water maze. The injection of the GR antagonist after training resulted in increased latencies to find the platform, which reflects the disturbed consolidation of spatial information. Corticosteroids affect in a differential and coordinated manner behavioral strategies and storage of spatial information. PMID- 1313245 TI - Adenoid cystic carcinoma of the palate. AB - We reviewed the clinical records of 41 patients who received definitive treatment for adenoid cystic carcinoma arising from the palate. Tumors were divided into three categories depending on local extension and pattern of growth. Surgery, either alone or in combination with post-operative radiation therapy, yielded satisfactory local regional control of the cancer. Patients who had adenoid cystic carcinoma with diffuse microscopic spread into adjacent tissues had the highest propensity for the development of distant metastases. PMID- 1313246 TI - Juvenile nasopharyngeal angiofibroma tumor models. Failure of androgens to stimulate growth in nude mice and in vitro. AB - Juvenile nasopharyngeal angiofibroma is a tumor with a predilection for adolescent boys. It has been shown to contain cytosolic androgen receptors and to regress with estrogen therapy; however, the results have not been consistent. Extensive investigation has been unable to settle this issue in patients owing, in part, to the rarity of these tumors. We have attempted to establish a tumor model for juvenile nasopharyngeal angiofibroma by transplanting the tumor into the subdermal space of athymic mice and also by culturing it in vitro, to study the effect of hormonal manipulation. The tumor did survive in male and female athymic mice but has failed to grow. Androgen treatment of the mice of either sex did not alter its survival or growth behavior. The in vitro tissue culture grew fibroblastoid cells that were not stimulated by androgen supplementation. This study suggests that factors other than androgens are at least complementary, if not essential, in promoting the growth of juvenile nasopharyngeal angiofibroma in tumor models, and that androgens are not, in and of themselves, sufficient growth stimuli. PMID- 1313247 TI - Management of dysphagia in inclusion body myositis. AB - Inclusion body myositis is an inflammatory myopathy in which dysphagia has been considered a rare finding. However, recent literature finds dysphagia an increasingly common symptom as more cases of inclusion body myositis are identified. Unlike some inflammatory myopathic disorders, inclusion body myositis is resistant to treatment with corticosteroids, and therefore, the otolaryngologist may be consulted regarding surgical options for relief of dysphagia. A patient is described in whom severe progressive dysphagia associated with inclusion body myositis developed. Impaired pharyngeal wall motion and cricopharyngeal achalasia were demonstrated by videofluoroscopic evaluation, and the patient was successfully treated by cricopharyngeal myotomy. The pathophysiologic nature of inclusion body myositis and the mechanisms of cervical dysphagia in the inflammatory myopathies are reviewed. PMID- 1313248 TI - Factors influencing survival in ethmoid sinus cancer. AB - Nineteen patients with primary ethmoid sinus malignancies were treated at the Cleveland (Ohio) Clinic Foundation between 1976 and 1989. Pathologic diagnoses included adenocarcinoma (eight), sarcoma (four), squamous cell carcinoma (three), mucoepidermoid carcinoma (two), adenoid cystic carcinoma (one), and undifferentiated carcinoma (one). All patients underwent surgical resection: 13 had craniofacial resection, four had craniofacial resection/orbital exenteration, one had radical ethmoidectomy/maxillectomy/orbital exenteration, and one had transantral ethmoidectomy. Twelve patients had combined treatment with radiation therapy. Ten patients were alive with no evidence of disease. A trend toward improved prognosis is associated with negative surgical margins. Preservation of the globe was not associated with local recurrence at this site. A poor prognosis was noted with involvement of the dura, brain, nasopharynx, or sphenoid sinus. PMID- 1313249 TI - Facial paralysis due to benign parotid tumors. AB - On rare occasions, facial paralysis associated with a parotid tumor need not denote malignancy. We present two cases in which, contrary to appropriate conventional wisdom, facial paralysis resulted from benign mixed tumors. Each patient presented over 8 years following primary surgical excision. In neither patient was a mass palpable, and facial paralysis was the sole sign of recurrent disease. Each patient had been followed up for several months with a presumptive diagnosis of Bell's palsy prior to discovery of recurrent tumor by radiologic imaging. In each case, at operation the tumor was found to infiltrate the temporal bone via the stylomastoid foramen. Facial paralysis presumably resulted from extrinsic compression of the facial nerve. These two cases add to the few previous reports of facial paralysis due to benign parotid gland tumors. PMID- 1313250 TI - Severity of rotavirus infection in relation to serotype, monotype and electropherotype. AB - The aim of this study was to determine whether the severity of symptoms associated with rotavirus infection was related to the serotype of the infecting virus. Severity of clinical symptoms in 108 children admitted to hospital for treatment of rotavirus diarrhoea was retrospectively assessed using a scoring system for frequency and duration of vomiting and diarrhoea, degree of fever, acidosis and dehydration, and presence of electrolyte imbalance. Children were 6 30 months old and were fully weaned at onset of symptoms prior to admission to hospital. No other enteric pathogens were detected during the course of the illness. Serotypes and monotypes were identified using a panel of monoclonal antibodies. Gel electrophoresis of rotavirus RNA was performed to determine electropherotypes. Children surveyed were infected with serotype 1 (47), serotype 2 (15) or serotype 4 (46) rotaviruses. Comparisons of severity of clinical symptoms according to infecting serotype revealed no statistically significant differences between serotype 1, 2 or 4 infections. In addition, no differences were detected between different rotavirus strains within each serotype (as judged by electropherotype) including monotypes 1a or 1c. This study failed to reveal differences in virulence between rotavirus strains of different VP7 serotypes infecting young children. PMID- 1313251 TI - Cyclic AMP turnover in intact tissue. Role of cyclic nucleotide phosphodiesterases. PMID- 1313252 TI - 2',3'-Cyclic-nucleotide 3'-phosphodiesterase. Complementary DNA and gene cloning for mouse enzyme and in situ hybridization of the messenger RNA in mouse brain. PMID- 1313253 TI - Regional and developmental expression of calmodulin-dependent cyclic nucleotide phosphodiesterase in rat brain. PMID- 1313254 TI - Histo- and cytochemical demonstration of cyclic nucleotide phosphodiesterase activity in the rat outer retina. PMID- 1313256 TI - The GTP-binding protein-dependent activation and deactivation of cyclic GMP phosphodiesterase in rod photoreceptors. PMID- 1313255 TI - Use of the yeast low-Km cAMP-phosphodiesterase gene to control cyclic AMP levels in mammalian cells. PMID- 1313257 TI - Mechanisms for activation of the rat adipocyte particulate cyclic-GMP-inhibited cyclic AMP phosphodiesterase and its importance in the antilipolytic action of insulin. PMID- 1313258 TI - Regulatory mechanisms of particulate cyclic nucleotide phosphodiesterases. PMID- 1313259 TI - Demonstration of functional compartments of cyclic AMP in rat platelets by the use of phosphodiesterase inhibitors. PMID- 1313260 TI - Development of molecular probes for the research of calmodulin-dependent enzymes. PMID- 1313261 TI - Cyclic nucleotide phosphodiesterases in the circulatory system. Biochemical, pharmacological, and functional characteristics. PMID- 1313262 TI - Calcium-calmodulin-stimulated and cyclic-GMP-specific phosphodiesterases. Tissue distribution, drug sensitivity, and regulation of cyclic GMP levels. PMID- 1313263 TI - Catalytic and regulatory properties of calmodulin-stimulated phosphodiesterase isozymes. PMID- 1313264 TI - Tissue and species specificity of cardiac cAMP-phosphodiesterase inhibitors. PMID- 1313265 TI - Structural requirements for potent and selective inhibition of low-Km, cyclic-AMP specific phosphodiesterases. PMID- 1313266 TI - Comparative studies on cyclic nucleotide phosphodiesterases and inhibitors in experimental models of hypertension, congestive heart failure, and allergic asthma. PMID- 1313267 TI - Relaxant effects of various xanthine derivatives. Relationship to cyclic nucleotide phosphodiesterase inhibition. PMID- 1313268 TI - Cyclic AMP phosphodiesterase from human heart and drug action. PMID- 1313269 TI - Phosphodiesterase inhibitors as antiplatelet agents in vascular surgery. PMID- 1313270 TI - Clinical studies of phosphodiesterase inhibitors for cardiovascular disease. PMID- 1313271 TI - Partial mapping of cyclic nucleotide sites and studies of regulatory mechanisms of phosphodiesterases using cyclic nucleotide analogues. PMID- 1313272 TI - Sequence homology and structure--function studies of the bovine cyclic-GMP stimulated and retinal phosphodiesterases. PMID- 1313273 TI - Low-Km cyclic AMP phosphodiesterase from human platelets. Stimulation of activity by phosphorylation of the enzyme and affinity labeling of the active site. PMID- 1313274 TI - Structure and regulation of the rat high-affinity cyclic AMP phosphodiesterases. A family of closely related enzymes. PMID- 1313276 TI - Management of tumors of the trachea. AB - Experience in the management of primary tracheal tumors remains small because of their rarity. Adenoidcystic carcinoma (40%) and squamous cell carcinoma off%) are the most common histologies. They present with signs of airway obstruction or hemoptysis and are delineated by bronchoscopy, tomography, and CT scan. Two thirds of all tracheal tumors are resectable, followed by airway reconstruction. Postoperative irradiation appears to be indicated for malignant tumors. Surgical mortality in 147 resections was 5%, with most deaths following carinal reconstruction. Twenty of 41 patients with squamous cell carcinomas who underwent resection are alive without disease (some for more than 25 years) and 39 of 52 with adenoidcystic carcinoma (some for as long as 19 years). PMID- 1313275 TI - Beta endorphin release in patients after spontaneous and provoked acute myocardial ischaemia. AB - BACKGROUND: In animal models of circulatory shock and heart failure concentrations of the endogenous opioid peptide beta endorphin are raised and opioid receptor blockade improves haemodynamic variables and survival. This study was performed to identify whether acute myocardial ischaemia provokes the release of beta endorphin in humans. METHODS: Observational study in a university cardiology centre. Serial measurements of beta endorphin made by specific radioimmunoassay were correlated with other clinical and neuroendocrine variables that were measured prospectively. Fifty five patients with acute myocardial ischaemia and 26 patients undergoing elective coronary angioplasty of the left anterior descending coronary artery were studied. RESULTS: beta endorphin concentrations were raised above the upper limit of normal in 31/42 (74%) patients with confirmed myocardial infarction, 3/13 (23%) patients with unstable angina, and 10/24 (42%) patients after coronary angioplasty. There was no evidence of myocardial release of beta endorphin. There were significant positive correlations between beta endorphin and the concentrations of adrenocorticotrophic hormone, cortisol, and arginine vasopressin. In patients with acute myocardial ischaemia there was a significant positive correlation between the peak concentrations of creatine kinase and beta endorphin but no correlation with visual analogue scores of the intensity of chest pain. The highest beta endorphin concentrations were seen in patients whose clinical course was complicated by the development of heart failure. CONCLUSIONS: beta endorphin release is a component of the neuroendocrine activation associated with myocardial ischaemia/infarction. PMID- 1313277 TI - Increased calmodulin levels in fibroblasts from progressive systemic sclerosis. AB - Calmodulin levels in cultured skin fibroblasts from patients with progressive systemic sclerosis (PSS) and healthy controls were measured by their ability to activate cyclic AMP-phosphodiesterase. Calmodulin levels were significantly increased in PSS fibroblasts compared with normal control fibroblasts. The changes in calmodulin content of PSS fibroblasts were also assessed by a radioimmunoassay. These findings suggest that an elevated level of calmodulin may play a role in the pathogenesis of PSS. PMID- 1313278 TI - The role of iron in an acute model of skin inflammation induced by reactive oxygen species (ROS). AB - The effect of iron was studied in rats in a ROS-initiated model of acute skin inflammation. Iron dextran was administered i.v. 24 h before the induction of the inflammatory response by intradermal injection of glucose oxidase attached to polyethylene glycol (GOD-PEG). Iron exacerbated the response at 24 and 48 h (P greater than 0.001). Histologically, a similar picture was seen to that without iron except for an increase in tissue oedema and matrix destruction including the skin glands. Associated with iron loading was an increase in Perls stainable iron in the skin (P greater than 0.025) and liver (P greater than 0.001). However, skin inflammation without iron loading also increased skin iron levels (P greater than 0.025). Total serum iron was decreased in iron-loaded and GOD-PEG animals (P greater than 0.01) and the unbound iron binding capacity (UIBC) increased (P greater than 0.01). PMID- 1313279 TI - A case of skin hyperpigmentation due to alpha-MSH hypersecretion. AB - A case is presented of generalized skin hyperpigmentation due to alpha-MSH hypersecretion from the pituitary that was most marked in the light-exposed areas. The patient also had secondary adrenal dysfunction, peripheral lymphadenopathy, streptococcal glomerulonephritis and malabsorption. Analysis of this patient's alpha-MSH using high-pressure liquid chromatography (HPLC) showed a novel acetylation profile compared to normal individuals and to patients with Cushing's disease and Nelson's syndrome. Glucocorticoid replacement therapy resulted in suppression of alpha-MSH hypersecretion and complete resolution of the illness. PMID- 1313280 TI - What makes silica toxic? AB - Published data suggest that particle charge could be related to its toxicity. Respirable particles containing silica were therefore collected in foundries and their charge measured. These particles carried high levels of positive charge that were related to low humidity. Incubating these particles with pulmonary macrophages from mice produced detectable activities of collagenase, a precursor of silicosis. These experiments confirm that the toxicity of silica particles is likely to be because of the positive charge they carry. PMID- 1313282 TI - The association of germ cell tumours of the testis with sarcoid-like processes. AB - Sarcoid-type pulmonary lymphadenopathy associated with testicular cancer is a rare condition which has been previously reported in only 14 cases. Earlier case reports have failed to distinguish between generalized sarcoidosis as opposed to a local granulomatous reaction to tumour. We describe a further 8 cases of the association and provide strong supportive evidence for systemic sarcoidosis in 5 of our patients. In 3 of our patients with systemic sarcoidosis there was coexisting testicular cancer requiring additional treatment. We therefore advise caution in the interpretation of the clinical and histological findings in these patients, and recommend thorough investigation of all such cases. PMID- 1313281 TI - A nested case-control study of lung cancer among silica exposed workers in China. AB - In an attempt to assess whether silica induces lung cancer, a nested case-control study of 316 male lung cancer cases and 1352 controls was carried out among pottery workers and tungsten, copper-iron, and tin miners from five provinces in south central China. Exposure to dust and silica for each study subject was evaluated quantitatively by cumulative exposure measures based on historical industrial hygiene records. Measurements on confounders such as inorganic arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon were also collected from the worksites. Information on cigarette smoking was obtained by interviews of the subjects or their next of kin. A significant trend of increasing risk of lung cancer with exposure to silica was found for tin miners, but not for miners working in tungsten or copper-iron mines. Concomitant and highly correlated exposures to arsenic and PAHs among tin miners were also found. Risk of lung cancer among pottery workers was related to exposure to silica, although the dose response gradient was not significant. Risks of lung cancer were significantly increased among silicotic subjects in iron-copper and tin mines, but not in pottery factories or tungsten mines. The results of this study provide only limited support for an aetiological association between silica and lung cancer. PMID- 1313283 TI - Endothelins belong to the assortment of mast cell-derived and mast cell-bound cytokines. AB - Local accumulation of endothelins (ETs) as cytokine-like factors via autocrine/paracrine mechanisms seems to represent an important aspect of their pathophysiological action. This assumption prompted us to investigate mast cells as a possible source of these peptides. With the use of a combination of high performance liquid chromatography and a radioimmunoassay specific for endothelin 1 (ET-1), 3-week-old cultures of primary murine bone marrow mast cells (BMMC) as well as various mast cell lines were shown to contain and secrete immunoreactive ET-1. The amounts of this peptide were constitutively high in cellular extracts of BMMC, while there was considerable variation in the basal cellular content among mast cell lines, ranging from high (C57) to undetectable (RBL) levels. Treatment of the cells with the combination of phorbol myristate acetate (PMA) and A23187 for 5 h led to induction of ET-1 production in all cases tested. In contrast to the rapid stimulation by PMA/A23187 of histamine release from BMMC or C57 cells, however, no ET-1 secretory response was noted as early as 30 min after this combined treatment. Moreover, stimulation of mast cells with crosslinked IgE for 30 min or 5 h did not affect ET-1 secretion, suggesting that mast cell ET-1 release is not directly related to mast cell degranulation. After exposure of the cells to crosslinked IgE for 20 h, however, there was a distinct increase in immunoreactive ET-1 in the medium, to approximate 10 times the basal level. Polymerase chain reaction (PCR) analysis of mRNA expression in mast cells revealed that the amount of ET-1 PCR product, which is low or undetectable under nonstimulated conditions, is enhanceable by both PMA/A23187 and crosslinked IgE. The IgE-mediated induction kinetics for ET-1 mRNA parallel the kinetics obtained with PMA/A23187, albeit at somewhat lower levels. With the use of fluorescent ligand binding/flow cytometry as a screening method and a radioreceptor assay as the confirming method, mast cells were found to express a single class of high affinity ET receptors with distinct selectivity for ET-1 and a pharmacological profile resembling that of the ETA type ET receptor. Stimulation of mast cell ET 1 receptors did not provoke histamine release, nor did it result in a mitogenic response of BMMC. In conclusion, mast cells synthesize and secrete ET-1 and have ET receptors, suggesting that ET-1 may participate in mediating mast cell-related long-term changes in the microenvironment, e.g., in smooth muscle tone or the proliferation rate of fibroblasts. PMID- 1313284 TI - Atmospheric carbon dioxide: a plant fertilizer? PMID- 1313285 TI - WT1: a novel tumor suppressor gene inactivated in Wilms' tumor. AB - The development of Wilms' tumor, a pediatric kidney cancer, has been linked to the inactivation of a tumor suppressor gene both by epidemiologic studies and by genetic analyses. Like retinoblastoma, Wilms' tumors can occur bilaterally in individuals with apparent genetic susceptibility to this disease. This led Knudson and Strong to propose in 1972 that two genetic events were rate limiting in tumor development and that predisposed individuals had already inherited one mutation in the germline. The observation of karyotype abnormalities in predisposed children and studies of the molecular genetics of Wilms' tumor specimens enabled the identification of chromosome band 11p13 as one genetic locus inactivated in Wilms' tumor. The recent isolation of the WT1 gene, which is the specific target within that locus, offers new insight into the etiology of Wilms' tumor. This gene has properties distinct from those of other known tumor suppressor genes. WT1 encodes a zinc finger transcription factor that is alternatively spliced and has high sequence homology to the early growth response genes (EGR). Unlike the retinoblastoma (RB1) and p53 genes that are expressed ubiquitously, WT1 is expressed in specific cells of the kidney and only during a short period in development. Thus, disruption of a gene that is active during a critical period in the development of a specific organ can lead to neoplastic growth in that organ. Future studies are aimed at exploring the link between the role of the WT1 gene in normal development and in tumorigenesis of the kidney. PMID- 1313286 TI - Xanthine dehydrogenase from Drosophila melanogaster: purification and properties of the wild-type enzyme and of a variant lacking iron-sulfur centers. AB - Xanthine dehydrogenase has been purified to homogeneity by conventional procedures from the wild-type strain of the fruit fly Drosophila melanogaster, as well as from a rosy mutant strain (E89----K, ry5231) known to carry a point mutation in the iron-sulfur domain of the enzyme. The wild-type enzyme had all the specific properties that are peculiar to the molybdenum-containing hydroxylases. It had normal contents of molybdenum, the pterin molybdenum cofactor, FAD, and iron-sulfur centers. EPR studies showed its molybdenum center to be quite indistinguishable from that of milk xanthine oxidase. As isolated, only about 10% of the enzyme was present in the functional form, with most or all of the remainder as the inactive desulfo form. It is suggested that this may be present in vivo. Extensive proteolysis accompanied by the development of oxidase activity took place during isolation, but dehydrogenase activity was retained. EPR properties of the reduced iron-sulfur centers, Fe-SI and Fe-SII, in the enzyme are very similar to those of the corresponding centers in milk xanthine oxidase. The E89----K mutant enzyme variant was in all respects closely similar to the wild-type enzyme, with the exception that it lacked both of the iron sulfur centers. This was established both by its having the absorption spectrum of a simple flavoprotein and by the complete absence of EPR signals characteristic of iron-sulfur centers in the reduced enzyme. Despite the lack of iron-sulfur centers, the mutant enzyme had xanthine:NAD+ oxidoreductase activity indistinguishable from that of the wild-type enzyme. Stopped-flow measurements indicated that, as for the wild-type enzyme, reduction of the mutant enzyme was rate-limiting in turnover. Thus, the iron-sulfur centers appear irrelevant to the normal turnover of the wild-type enzyme with these substrates. However, activity to certain oxidizing substrates, particularly phenazine methosulfate, is abolished in the mutant enzyme variant. This is one of the first examples of deletion by genetic means of iron-sulfur centers from an iron-sulfur protein. The relevance of our findings both to the roles of iron-sulfur centers in other systems and to the nature of the oxidizing substrate for the Drosophila enzyme in vivo are briefly discussed. PMID- 1313287 TI - Cytochrome bc1 complex [2Fe-2S] cluster and its interaction with ubiquinone and ubihydroquinone at the Qo site: a double-occupancy Qo site model. AB - The ubiquinone complement of Rhodobacter capsulatus chromatophore membranes has been characterized by its isooctane solvent extractability and electrochemistry; we find that the main ubiquinone pool (Qpool) amounts to about 80% of the total ubiquinone and has an Em7 value close to 90 mV. To investigate the interactions of ubiquinone with the cyt bc1 complex, we have examined the distinctive EPR line shapes of the [2Fe-2S] cluster of the cyt bc1 complex when the Qpool-cyt bc1 complex interactions are modulated by changing the numbers of Q or QH2 present (by solvent extraction and reconstitution), by the exposure of the [2Fe-2S] to the Qpool in different redox states, by the presence of inhibitors specific for the Qo site (myxothiazol and stigmatellin) and Qi site (antimycin), and by site specific mutations of side chains of the cyt b polypeptide (mutants F144L and F144G) previously identified as important for Qo site structure. Evidence suggests that the Qo site can accommodate two ubiquinone molecules. One (designated Qos) is bound relatively strongly and is second only to the ubiquinone of the QA site of the reaction center in its resistance to solvent extraction. In this strong interaction, the Qo site binds Q and QH2 with approximately equal affinities. Their bound states are distinguished by their effects on the [2Fe-2S] cluster spectral feature at gx at 1.783 (Q) and gx at 1.777 (QH2); titration of the line-shape change reveals an Em7 value of approximately 95 mV. The other molecule (Qow) is bound more weakly, in the same range as the ubiquinone of the QB site of the reaction center. Again, the affinities of the Q form (gx at 1.800) and QH2 form (gx at 1.777) are nearly equal, and the Em7 value measured is approximately 80 mV. These results are discussed in terms of earlier EPR analyses of the cyt bc1 complexes of other systems. A Qo site double-occupancy model is considered that builds on the previous model based on Qo site mutants [Robertson, D. E., Daldal, F.,& Dutton, P. L. (1990) Biochemistry 29, 11249-11260] and includes the recent suggestion that two of the [2F3-2S] cluster ligands of the R. capsulatus cyt bc1 complex are histidines [Gurbiel, R. J. Ohnishi, T., Robertson, D. E. Daldal, F., & Hoffman, B. M. (1991) Biochemistry 30, 11579-11584]. We speculate that the cyt bc1 complex complexes a full enzymatic turnover without necessary exchange of ubiquinone with the Qpool. PMID- 1313288 TI - Binding of calcium by calmodulin: influence of the calmodulin binding domain of the plasma membrane calcium pump. AB - The interaction between calmodulin and synthetic peptides corresponding to the calmodulin binding domain of the plasma membrane Ca2+ pump has been studied by measuring Ca2+ binding to calmodulin. The largest peptide (C28W) corresponding to the complete 28 amino acid calmodulin binding domain enhanced the Ca2+ affinity of calmodulin by more than 100 times, implying that the binding of Ca2+ increased the affinity of calmodulin for the peptide by more than 10(8) times. Deletion of the 8 C-terminal residues from peptide C28W did not decrease the affinity of Ca2+ for the high-affinity sites of calmodulin, but it decreased that for the low affinity sites. A larger deletion (13 residues) decreased the affinity of Ca2+ for the high-affinity sites as well. The data suggest that the middle portion of peptide C28W interacts with the C-terminal half of calmodulin. Addition of the peptides to a mixture of tryptic fragments corresponding to the N- and C-terminal halves of calmodulin produced a biphasic Ca2+ binding curve, and the effect of peptides was different from that on calmodulin. The result shows that one molecule of peptide C28W binds both calmodulin fragments. Interaction of the two domains of calmodulin through the central helix is necessary for the high affinity binding of four Ca2+ molecules. PMID- 1313290 TI - Spin-label electron paramagnetic resonance and differential scanning calorimetry studies of the interaction between mitochondrial cytochrome c oxidase and adenosine triphosphate synthase complex. AB - The interaction between cytochrome c oxidase complex and adenosine triphosphate synthase (F1F0) complex in the purified, dispersed state and embedded in phospholipid vesicles was studied by differential scanning calorimetry and by spin-label electron paramagnetic resonance. The detergent-dispersed cytochrome oxidase and F1F0 complexes undergo endothermic thermodenaturation. However, when these complexes are embedded in phospholipid vesicles, they undergo exothermic thermodenaturation. The energy released is believed to result from the collapse of a strained interaction between unsaturated fatty acyl groups of phospholipids and an exposed area of the complex formed by the removal of interacting proteins. The exothermic enthalpy change of thermodenaturation of a protein-phospholipid exothermic enthalpy change of thermodenaturation of a protein-phospholipid vesicle containing both cytochrome oxidase complex and F1F0 was smaller than that of a mixture of protein-phospholipid vesicles formed from each individual electron transfer complex. This suggests specific interaction between cytochrome oxidase complex and F1F0 in the membrane. Further evidence for interaction between these two complexes is provided by saturation transfer EPR studies in which the rotational correlation time of spin-labeled cytochrome oxidase increases significantly when the complex is mixed with F1F0 prior to being embedded in phospholipid vesicles. From these results, it is concluded that at least a part of cytochrome oxidase and a part of F1F0 form a supermacromolecular complex in the inner mitochondrial membrane. No such supermacromolecular complex is detected between F1F0 and ubiquinol--cytochrome c reductase. PMID- 1313289 TI - Biochemical and spectroscopic characterization of the high molecular weight cytochrome c from Desulfovibrio vulgaris Hildenborough expressed in Desulfovibrio desulfuricans G200. AB - The gene of high molecular weight, multiheme cytochrome c (Hmc) from the sulfate reducing bacterium Desulfovibrio vulgaris Hildenborough has been overexpressed in Desulfovibrio desulfuricans G200. The recombinant protein has been purified. Its molecular weight (65,600), amino acid composition, and NH2-terminal sequence were found to be identical to those of the wild-type protein. The recombinant protein has been spectroscopically characterized (optical spectrum, EPR, circular dichroism) and compared to the wild-type protein. We have found 16 hemes per molecule by iron analysis and the pyridine hemochrome test. Both high- and low spin features were observed in the EPR spectrum. A detailed spin quantitation analysis indicates 1 or 2 high-spin hemes and 14 or 15 low-spin hemes per molecule. The redox potentials of the hemes determined by voltammetric techniques gave an average of three different values, 0, -100, and -250 mV (versus NHE), for the wild-type and the recombinant cytochrome. The low potential values are similar to the values observed for the bis(histidinyl) coordinated hemes of cytochrome c3. A comparison of the arrangement of heme binding sites and coordinated histidines in the amino acid sequences of cytochrome c3 and Hmc has shown that the latter contains four domains, three of which are complete c3-like domains, while the fourth represents an incomplete c3-like domain which may contain His-Met coordinated hemes. These data are in agreement with the detailed study of the number and types of hemes reported in this paper. PMID- 1313291 TI - The YF161D1 mutant of Synechocystis 6803 exhibits an EPR signal from a light induced photosystem II radical. AB - The currently accepted model for the location of the redox-active tyrosines, D and Z, in photosystem II suggests that they are symmetrically located on the D1 and D2 polypeptides, which are believed to form the heterodimer core of the reaction center. Z, the electron conduit from the manganese catalytic site to the primary chlorophyll donor, has been identified with tyrosine-161 of D1. The YF161D1 mutant of Synechocystis 6803 [Debus, R. J., Barry, B. A., Sithole, I., Babcock, G. T., & McIntosh, L. (1988b) Biochemistry 27, 9071-9074; Metz, J. G., Nixon, P. J., Rogner, M., Brudvig, G. W., & Diner, B. A. (1989) Biochemistry 28, 6960-6969], in which this tyrosine has been changed to a phenylalanine, should have no light-induced EPR (electron paramagnetic resonance) signal from a tyrosine radical. This negative result has indeed been obtained in analysis of one of two independently constructed mutants through the use of a non-oxygen evolving core preparation (Metz et al., 1989). Here, we present an analysis of a YF161D1 mutant through the use of a photosystem II purification procedure that gives oxygen-evolving particles from wild-type Synechocystis cultures. In our mutant preparation, a light-induced EPR signal from a photosystem II radical is observed under conditions in which, in a wild-type preparation, we can accumulate an EPR signal from Z+. This EPR signal has a different lineshape from that of the Z+ tyrosine radical, and spin quantitation shows that this radical can be produced in up to 60% of the mutant reaction centers. The EPR lineshape of this radical suggests that photosystem II reaction centers of the YF161D1 mutant contain a redox-active amino acid. PMID- 1313292 TI - Potential ligands to the [2Fe-2S] Rieske cluster of the cytochrome bc1 complex of Rhodobacter capsulatus probed by site-directed mutagenesis. AB - The Rieske protein of the ubiquinol-cytochrome c oxidoreductase (bc1 complex or b6f complex) contains a [2Fe-2S] cluster which is thought to be bound to the protein via two nitrogen and two sulfur ligands [Britt, R. D., Sauer, K., Klein, M. P., Knaff, D. B., Kriauciunas, A., Yu, C.-A., Yu, L., & Malkin, R. (1991) Biochemistry 30, 1892-1901; Gurbiel, R. J., Ohnishi, T., Robertson, D. E., Daldal, F., & Hoffman, B. M. (1991) Biochemistry 30, 11579-11584]. All available Rieske amino acid sequences have carboxyl termini featuring two conserved regions containing four cysteine (Cys) and two or three histidine (His) residues. Site directed mutagenesis was applied to the Rieske protein of the photosynthetic bacterium Rhodobacter capsulatus, and the mutants obtained were studied biochemically in order to identify which of these conserved residues are the ligands of the [2Fe-2S] cluster. It was found that His159 (in the R. capsulatus numbering) is not a ligand and that the presence of the Rieske protein in the intracytoplasmic membrane is greatly decreased by alteration of any of the remaining six His or Cys residues. Among these mutations, only the substitution Cys155 to Ser resulted in the synthesis of Rieske protein (in a small amount) which contained a [2Fe-2S] cluster with altered biophysical properties. This finding suggested that Cys155 is not a ligand to the cluster. A comparison of the conserved regions of the Rieske proteins with bacterial aromatic dioxygenases (which contain a spectrally and electrochemically similar [2Fe-2S] cluster) indicated that Cys133, His135, Cys153, and His156 are conserved in both groups of enzymes, possibly as ligands to their [2Fe-2S] clusters. These findings led to the proposal that Cys138 and Cys155, which are not conserved in bacterial dioxygenases, may form an internal disulfide bond which is important for the structure of the Rieske protein and the conformation of the quinol oxidation (Qo) site of the bc1 complex. PMID- 1313293 TI - Rhodobacter capsulatus mutants lacking the Rieske FeS protein form a stable cytochrome bc1 subcomplex with an intact quinone reduction site. AB - The ubiquinol-cytochrome c oxidoreductase (or bc1 complex) of Rhodobacter capsulatus consists of three subunits: cytochrome b, cytochrome c1, and the Rieske iron-sulfur protein, encoded by the fbcF, fbcB, and fbcC genes, respectively. In the preceding paper [Davidson, E., Ohnishi, T., Atta-Asafo Adjei, E., & Daldal, F. (1992) Biochemistry (preceding paper in this issue)], we have observed that the apoproteins for cytochromes b and c1 are fully present in the intracytoplasmic membrane of R. capsulatus mutants containing low amounts of, or no, Rieske apoprotein. Here we present evidence that the redox midpoint potentials of cytochromes b and c1, as well as their ability to bind antimycin and stabilize a semiquinone at the Qi site, are unaffected by the absence of the Rieske subunit. This is the first report describing a mutant containing a stable bc1 subcomplex with an intact Qi site in the chromatophore membranes, and provides further evidence that a functional quinone reduction site can be formed in the absence of a quinol oxidation (Qo) site. Additional mutants carrying fbc deletions expressing the remaining subunits of the cytochrome bc1 complex were constructed to investigate the relationship among these subunits for their stability in vivo. Western blot analysis of these mutants indicated that cytochromes b and c1 protect each other against degradation, suggesting that they form a two-protein subcomplex in the absence of the Rieske protein subunit. PMID- 1313294 TI - Expression and characterization of recombinant hepatitis A virus 3C proteinase. AB - The 3C proteinase from the hepatitis A virus (HAV) was cloned into a multicopy expression vector in Escherichia coli under control of the tac promoter. The resulting plasmid construction produced 3C proteinase as a soluble and active enzyme constituting approximately 10% of total cellular proteins. The enzyme was purified to apparent homogeneity as judged by SDS gel electrophoresis and HPLC reversed-phase and FPLC ion-exchange chromatography. A colorimetric assay was developed, and synthetic peptides derived from the predicted cleavage sites of the HAV polyprotein were tested for proteolysis of the enzyme. The peptide representing the 2B/2C cleavage site was cleaved most efficiently with a Km and kcat of 2.1 +/- 0.5 mM and 1.8 +/- 0.1 s-1, respectively. Site-directed mutagenesis was then used to identify the cysteine at position 172 as the active site nucleophile. Finally, the purified enzyme showed the expected endoproteinase activity on the P1 precursor protein generated by in vitro transcription/translation. PMID- 1313295 TI - Direct relationship between intracellular calcium mobilization and phospholipase D activation in prostaglandin E-stimulated human erythroleukemia cells. AB - The relationship between calcium mobilization and phospholipase D (PLD) activation in response to E-series prostaglandins (PGEs) was investigated in human erythroleukemia cells. Intracellular free Ca2+ concentration ([Ca2+]i) was increased by PGE1 and PGE2 over the same concentration range at which PLD activation was seen. Pretreatment of cells with pertussis toxin greatly inhibited the PGE-stimulated increase in [Ca2+]i, implying that a G protein participates in the PGE receptor signaling process. The peak level and also the plateau level of Ca2+ mobilization stimulated by these prostaglandins were markedly decreased in Ca(2+)-depleted medium, indicating that both extracellular and intracellular Ca2+ stores contribute to the changes in [Ca2+]i. Likewise, activation of PLD by PGE1 and PGE2 was abolished by pertussis toxin pretreatment or incubation in Ca(2+) depleted medium. U73122, a putative phospholipase C inhibitor, blocked both Ca2+ mobilization and PLD activation in PGE-stimulated cells. Furthermore, the intracellular loading of BAPTA, a Ca2+ chelator, inhibited both Ca2+ mobilization and PLD activation by PGE1 and PGE2 in a similar dose-dependent manner. Simultaneous measurement of [Ca2+]i and PLD activity in the same cell samples indicated that PLD activity increases as a function of [Ca2+]i in a similar fashion in cells stimulated either by PGEs or by the calcium ionophore ionomycin. Taken together, these findings suggest that a rise in [Ca2+]i is necessary for PGE-stimulated PLD activity in human erythroleukemia cells. PMID- 1313296 TI - Photoinduced electron transfer between cytochrome c peroxidase and horse cytochrome c labeled at specific lysines with (dicarboxybipyridine)(bisbipyridine)ruthenium(II) AB - The reactions of yeast cytochrome c peroxidase with horse cytochrome c derivatives labeled at specific lysine amino groups with (dicarboxybipyridine)(bisbipyridine)ruthenium(II) [Ru(II)] were studied by flash photolysis. All of the derivatives formed complexes with cytochrome c peroxidase compound I (CMPI) at low ionic strength (2 mM sodium phosphate, pH 7). Excitation of Ru(II) to Ru(II*) with a short laser flash resulted in electron transfer to the ferric heme group in cytochrome c, followed by electron transfer to the radical site in CMPI. This reaction was biphasic and the rate constants were independent of CMPI concentration, indicating that both phases represented intracomplex electron transfer from the cytochrome c heme to the radical site in CMPI. The rate constants of the fast phase were 5200, 19,000, 55,000, and 14,300 s-1 for the derivatives modified at lysines 13, 25, 27, and 72, respectively. The rate constants of the slow phase were 260, 520, 200, and 350 s-1 for the same derivatives. These results suggest that there are two binding orientations for cytochrome c on CMPI. The binding orientation responsible for the fast phase involves a geometry that supports rapid electron transfer, while that for the slow phase allows only slow electron transfer. Increasing the ionic strength up to 40 mM increased the rate constant of the slow phase and decreased that of the fast phase. A single intracomplex electron transfer phase with a rate constant of 2800 s-1 was observed for the lysine 72 derivative at this ionic strength. When a series of light flashes was used to titrate CMPI to CMPII, the reaction between the cytochrome c derivative and the Fe(IV) site in CMPII was observed. The rate constants for this reaction were 110, 250, 350, and 140 s-1 for the above derivatives measured in low ionic strength buffer. PMID- 1313297 TI - DNA base modifications induced in isolated human chromatin by NADH dehydrogenase catalyzed reduction of doxorubicin. AB - The antineoplastic benzanthroquinone drug doxorubicin can undergo flavoenzyme catalyzed one-electron reduction which, in an aerobic environment, leads to the generation of oxygen-derived species. We therefore sought to determine whether doxorubicin in the presence of NADH dehydrogenase and the transition metal ions Fe(III) or Cu(II) induces DNA base modifications in isolated human chromatin. NADH dehydrogenase-catalyzed reduction of doxorubicin (25-100 microM) caused hydroxyl radical production detected as methane generated from dimethyl sulfoxide; addition of isolated human chromatin to the system produced a concentration-dependent quenching of detectable hydroxyl radical formation. Doxorubicin (5-50 microM)-stimulated enzyme-catalyzed oxidation of NADH was also diminished, but still detectable, in the presence of chromatin. Doxorubicin induced DNA base modifications in chromatin were measured by gas chromatography/mass spectrometry with selected-ion monitoring. Production of modified bases required the addition of transition metal ion and was enhanced by the addition of active flavoenzyme. The non-redox cycling analogue 5 iminodaunorubicin induced significantly less base modification than did doxorubicin. In the presence of Fe(III), NADH dehydrogenase-catalyzed reduction of doxorubicin caused enhancement in the content of all modified bases over control levels. Substitution of Cu(II) for Fe(III) altered both the degree and the pattern of doxorubicin/NADH dehydrogenase-induced base modifications. The scavengers of hydroxyl radical mannitol and dimethyl sulfoxide or catalase did not significantly affect doxorubicin/NADH/NADH dehydrogenase/transition metal ion induced base modifications. Superoxide dismutase further enhanced production of all base modifications. The data demonstrate that flavoenzyme-catalyzed redox cycling of doxorubicin generates typical hydroxyl radical-induced base modifications in the DNA of isolated human chromatin, suggesting a possible mechanism for the mutagenicity of doxorubicin in vivo. PMID- 1313298 TI - Purification and characterization of delta helicase from fetal calf thymus. AB - A DNA helicase (delta helicase) which partially copurifies with DNA polymerase delta has been highly purified from fetal calf thymus. delta helicase differs in physical and enzymatic properties from other eukaryotic DNA helicases described thus far. The enzyme has an apparent mass of 57 kDa by gel filtration and is associated with polypeptides of 56 and 52 kDa by SDS-polyacrylamide gel electrophoresis. Photo-cross-linking of the purified enzyme with [alpha-32P]ATP resulted in labeling of a polypeptide of approximately 58 kDa, suggesting that the active site is present on the larger polypeptide. Unwinding of a partial duplex requires a nucleoside triphosphate which can be either ATP or dATP but not a nonhydrolyzable analogue of ATP. Other ribo- and deoxyribonucleoside triphosphates have little or no activity as cofactors. delta helicase also has DNA-dependent ATPase activity which has a relatively low Km for ATP (40 microM). delta helicase binds to single-stranded DNA but has little or no affinity for double-stranded DNA or single-stranded RNA. Similar to replicative DNA helicases from prokaryotes and the herpes simplex virus type 1 helicase-primase, delta helicase translocates in the 5'-3' direction along the strand to which it is bound and preferentially unwinds DNA substrates with a forklike structure. PMID- 1313299 TI - Generation of polyclonal antibodies against the mineralocorticoid receptor and analysis of mineralocortin in rat myocardium by immunophotochemistry. AB - Fawn, Burgundy rabbits were immunized with the mineralocorticoid receptor (MCR) purified biochemically from rat kidney by a simple, two step procedure. High anti MCR titers were observed in radioimmunoassays just 3 weeks after the initial injection and increased further with time. Western blot analysis revealed a single band of 94-98 kDa in renal and cardiac cytosol from the rat, like the antigen prepared biochemically. The two atria from beef heart exhibited far greater MCR-positivity compared to the two ventricles, suggesting physiological relevance. The receptor was also photolabelled for the first time with promegestone in this very 94-98 kDa region which could be displaced by the antagonist RU 26752 specific to MCR. The immune IgG precipitated 3H-aldosterone or 3H-RU 26752-MCR complexes from rat heart, and displaced the MCR-antagonist complex to high molecular weight regions during gel permeation chromatography on Sephacryl columns. Immunofluorescent labelling showed that MCR was widely distributed in the cytoplasm in rat myocardium with limited staining in what appeared to be the nuclear compartment. These open up the possibility of large scale purification of the endogenous mineralocorticoid binding protein, mineralocortin, for detailed physicochemical characterization. The technique of photoaffinity labelling presented here should also help delineate the nature of the steroid binding domain in the MCR. PMID- 1313300 TI - Association of alpha-phosphatidylinositol-specific phospholipase C with phospholipid vesicles. AB - The alpha isoform of phosphatidylinositol-specific phospholipase C (alpha-PI-PLC, Mr 62,000) was purified from bovine brain. Enzyme activity was dependent on calcium, sodium cholate and showed the anticipated specificity for the phosphatidylinositols. Calcium interaction with this protein, investigated by gel filtration chromatography, showed no detectable binding at calcium concentrations adequate to activate the enzyme. Association of alpha-PI-PLC with phospholipid vesicles was studied by light scattering, fluorescence energy transfer and gel filtration chromatography. The enzyme readily associated with vesicles of high charge density, with vesicles of crude acidic phospholipids and with PIP2. Interaction was characterized by a rapid association followed by slower addition of more protein to the phospholipid. Complexes containing 20-30 percent protein (by weight) were readily obtained. Calcium had only a small effect on this interaction. The protein-phospholipid complexes appeared to bind less calcium than a similar amount of phospholipid alone. Thus, alpha-PI-PLC did not appear to be a calcium-binding protein in either its free or membrane-associated states. Although alpha-PI-PLC showed the highest propensity to bind to phospholipids, a number of other proteins also associated with phospholipids under the conditions used. Thus, whether or not the observed interaction of alpha-PI-PLC with membranes was specific and biologically important or whether it was a process common to many proteins, was not known. Knowledge of this interaction may enhance our understanding of possible mechanisms for protein-membrane interactions in general. PMID- 1313301 TI - Identification of protein phosphatase activities in maize seedlings. AB - Three phosphatases active on phosphocasein (PhosphoCasein Phosphatases) termed PCP-I, PCP-II and PCP-III were isolated from maize seedlings by DEAE-cellulose chromatography and were shown to display a different specificity toward a variety of phosphorylated substrates including pNPP, phosphohistones, phosphorylase a and several phosphopeptides containing either phosphoserine or phosphothreonine. PCP I and PCP-II bind to heparin-Sepharose, retain a remarkable pNPP activity, are uncapable to dephosphorylate phosphorylase a, and display striking activity toward the acidic phosphopeptide AS[32P]EEEEE. They also by far prefer phosphoseryl peptide RRAS[32P]VA over its phosphothreonyl derivative and are unsensitive to okadaic acid up to 1 microM. These properties are not consistent with the belonging of PCP-I and -II to any of the known classes of protein phosphatases and suggest that they are acidic phosphatases. Conversely, PCP-III is essentially free of pNPP activity; it readily dephosphorylates phosphohistone H1 and phosphorylase a and it displays a striking preference toward the phosphothreonyl peptides (RRAT[32P]VA and RRREEET[32P]EEEAA), while the phosphoseryl peptides (RRAS[32P]VA and AS[32P]EEEEE) are very poor substrates of the enzyme. These properties together with the findings that PCP-III does not bind to heparin-Sepharose and is highly sensitive to okadaic acid (IC50 = 0.2 nM) allow to identify PCP-III with a protein phosphatase of the PP-2A class. PMID- 1313302 TI - Cytochrome P-450(17 alpha,lyase)-mediating pathway of androgen synthesis in bovine adrenocortical cultured cells. AB - Cytochrome P-450(17 alpha,lyase) mediating pathway of dehydroepiandrosterone (DHA) formation from pregnenolone was investigated in primary cultures of bovine adrenocortical fasciculata-reticularis cells. To determine whether DHA formation proceeds predominantly by successive monooxygenase reactions without 17 alpha hydroxypregnenolone leaving P-450(17 alpha,lyase) the cells were incubated with [14C]pregnenolone and 17 alpha-[3H]hydroxypregnenolone in the presence of Trilostane. Results of the double-substrate double-label experiments indicate that in the presence of high concentration of pregnenolone most of DHA was formed, directly from pregnenolone by the successive reactions. Since the concentration of pregnenolone usually exceeds that of 17 alpha hydroxypregnenolone in the adrenal glands, DHA is concluded to be formed predominantly by successive reactions from pregnenolone without 17 alpha hydroxypregnenolone leaving P-450(17 alpha,lyase) in vivo. By chronic ACTH treatment, the activities of 17 alpha-hydroxylation and DHA formation in adrenocortical cultured cells became higher concomitantly with the increase of P 450(17 alpha,lyase) content. Most of DHA was found to be formed by successive reactions from pregnenolone even under such conditions. PMID- 1313303 TI - Purification and properties of the cGMP-inhibited cAMP phosphodiesterase from bovine aortic smooth muscle. AB - Pure cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) in micrograms quantities was isolated from bovine aortic smooth muscle after more than 5000-fold purification using DEAE ion-exchange and affinity chromatography with a derivative of the specific cGI-PDE inhibitor cilostamide conjugated as a ligand to aminoethyl agarose (CIT-agarose). The cGI-PDE, which constituted about half of the high affinity cAMP-PDE activity of a tissue homogenate, was identified with a 105-kDa protein on SDS-PAGE through use of antibodies towards the human platelet, bovine cardiac and bovine adipose tissue cGI-PDE in Western blot and immunoprecipitation/immunoinactivation analysis. As observed during purification of the enzyme from other tissues the enzyme protein was exquisitely sensitive to proteolytic nicking during purification, resulting in several 30-77-kDa polypeptide fragments. Rapid immunoprecipitation from fresh tissue extracts was the only was found to partially prevent the proteolysis. The native enzyme had apparent molecular sizes of approx. 100,000 or, mainly approx. 220,000 by gel chromatography, presumably indicating the presence of monomeric and dimeric forms. The enzyme hydrolyzed cAMP and cGMP with normal Michaelis-Menten kinetics with Km of 0.16 and 0.09 microM, respectively, with Vmax for hydrolysis of cAMP of 0.3 compared to 3.1 mumol/min per mg protein for cAMP. The enzyme was potently and selectively inhibited by cGMP (IC50 approximately 0.25 microM) and the cardiotonic/vasodilatory drugs OPC-3911 (a cilostamide derivative), milrinone and CI-930 (IC50 approximately 0.05, 0.40 and 0.25 microM, respectively). The cGI-PDE was phosphorylated by cAMP-dependent protein kinase as has been reported for the analogous enzymes in heart, adipose tissue and platelets. The identification of a cGI-PDE in the aortic smooth muscle and its inhibitor specificity is consistent with the hypothesis that inhibition of this enzyme is important in the mechanism through which these drugs produce vasorelaxation. PMID- 1313304 TI - Stable expression of recombinant human alpha 2-adrenoceptor subtypes in two mammalian cell lines: characterization with [3H]rauwolscine binding, inhibition of adenylate cyclase and RNase protection assay. AB - Cloning of the genes encoding distinct subtypes of human alpha 2-adrenergic receptors (alpha 2-AR) allows the separate recombinant expression of each individual subtype in heterologous systems. We report here the transfection, selection and preliminary pharmacological characterization of two mammalian cell lines, adherent Shionogi S115 mouse mammary tumour cells and human B lymphoblastoid IBW4 cells growing in suspension, expressing the human alpha 2-AR subtypes alpha 2-C4 and alpha 2-C10 at densities of approx. 2 x 10(5) receptors/cell. Transfection of the subtype genes was verified using a specific RNase protection assay. Pharmacological characterization was carried out with [3H]rauwolscine binding, which was inhibited by oxymetazoline and prazosin in a subtype-selective manner. The sensitivity of (-)-noradrenaline binding to the GTP analogue 5'-guanylylimidodiphosphate suggested that the receptors are coupled to G-proteins. This was verified in S115 cells by efficient inhibition of forskolin stimulated cAMP production by the alpha 2-AR agonists, (-)-noradrenaline and clonidine. These cell lines thus appear to be suitable for pharmacological studies on receptor function and ligand binding. PMID- 1313305 TI - Fatal disease in nursing puppies associated with minute virus of canines. AB - Thirteen cases of a previously undescribed parvoviral infection affecting puppies ranging in age from 5 to 21 days is described. The cases were originally thought to represent an unusual pathologic manifestation of canine parvovirus-2 (CPV-2) infection. However, failure to confirm CPV-2 infection in any of the cases suggested a different parvovirus was involved. Minute virus of canines (MVC) was subsequently isolated from a case by using the Walter Reed Canine Cell Line, the only cell line which will support the growth of MVC. The pathologic and virologic findings for these 13 cases are described in this report. PMID- 1313306 TI - Oral papillomavirus infection in a pygmy chimpanzee (Pan paniscus). PMID- 1313307 TI - Interspecies polymorphism of double-stranded RNA extracted from reoviruses of turkeys and chickens. PMID- 1313308 TI - Detection of bluetongue virus using a cDNA probe derived from genome segment 4 of bluetongue virus serotype 2. AB - The double-stranded (ds) RNA genome segment 4 of bluetongue virus (BTV) serotype 2 was cloned and used as a serogroup-specific complementary (c) DNA probe for BTV diagnosis. A cDNA representing a 60% copy of genome segment 4 BTV-2 prototype was produced. The specificity of the cDNA probe was determined by hybridizing this probe to a northern blot of dsRNA (separated by polyacrylamide gel electrophoresis) of plaque-purified BTV-2 prototype. This cDNA probe was then used to hybridize to the RNA samples. Because the probe hybridized to all BTV samples but not to epizootic hemorrhagic disease virus samples, it appears to be a group-specific probe that could be used in BTV diagnosis. PMID- 1313309 TI - [Diarrhea and enteral nutrition]. AB - The present study is a review of what is understood by diarrhoea and the factors leading to its development in patients on enteral nutrition. An analysis is made of the factors related to the preparation, administration and the factors concerning the patient. It has been observed that there are important discrepancies in the evaluation of diarrhoea provoked by enteral diets. This is due to the different definitions of diarrhoea, the method used and exclusion criteria used by different authors. PMID- 1313310 TI - Diet and inflammatory bowel disease: a case-control study. AB - We conducted a population-based case-control study of inflammatory bowel disease and dietary habits in Stockholm during 1984-1987. We obtained retrospective information about food intake 5 years previously by a postal questionnaire for 152 cases with Crohn's disease, 145 cases with ulcerative colitis, and 305 controls. The relative risk of Crohn's disease was increased for subjects who had a high (55 gm or more per day) intake of sucrose (relative risk = 2.6, 95% confidence interval = 1.4-5.0) and was decreased for subjects who had a high (15 gm or more per day) intake of fiber (relative risk = 0.5, 95% confidence interval = 0.3-0.9). The most striking finding was an increased relative risk of both Crohn's disease and ulcerative colitis associated with consumption of fast foods: the relative risk associated with consumption of fast foods at least two times a week was estimated at 3.4 (95% confidence interval = 1.3-9.3) for Crohn's disease and 3.9 (95% confidence interval = 1.4-10.6) for ulcerative colitis. Although coffee seemed to provide a protective effect for both diseases, there are reasons to consider this finding an artifact. PMID- 1313311 TI - Gender and histologic type variations in smoking-related risk of lung cancer. AB - We conducted a registry-based case-control study to examine the relation between smoking and lung cancer by gender and histologic type. Our analyses were based on 14,596 cases and 36,438 age-matched controls. Relative risk associated with ever smoking, and level of smoking was consistently higher in females than males for all lung cancers combined (ever-smoking odds ratios: 12.7 for females and 9.1 for males) and for each histologic type except adenocarcinoma. Female-male differences in relative risk were larger in younger age groups. The largest estimates of the attributable fraction due to smoking were observed for small cell carcinoma (97% in females and 91% in males); conversely, the smallest value was noted for adenocarcinoma (86% in females). Although our study was unable to measure absolute risk, our findings, other recent studies, and contemporary female smoking patterns raise concerns that female smokers may assume a proportionally greater burden of lung cancer morbidity and mortality in the future. PMID- 1313312 TI - Biology of B virus in macaque and human hosts: a review. AB - B virus is a zoonotic alpha-herpesvirus enzootic in Asian monkeys of the genus Macaca. At least 25 cases of human disease caused by B virus have occurred to date, leading to death in 16 instances. Advances in the technology available for the diagnosis of B virus infection and in the agents for its treatment are improving the prognosis for cases in human beings. Efforts are under way at several institutions in the United States to establish B virus-free colonies of rhesus macaques for use in biomedical research. Unfortunately, the epidemiology of B virus in group-housed macaques is poorly understood. The elucidation of factors important in the transmission of B virus between monkeys will greatly enhance efforts to eradicate this virus and may help to minimize further human exposure to the agent. PMID- 1313313 TI - Cytomegalovirus infection in patients with AIDS. AB - Advances in the field of antiviral therapy are now occurring with increasing frequency and rapidity and often generate varying degrees of confusion among those of us whose practices are focused primarily on therapy with antibacterial agents. How to treat cytomegalovirus infections in patients infected with the human immunodeficiency virus constitutes one of the best examples of the quandaries engendered by these advances, and the topic is reviewed in this first AIDS Commentary update. Given the U.S. Food and Drug Administration's recent approval of foscarnet, this discussion is very timely; it is particularly relevant for clinicians to be made aware of current lines of thought regarding induction versus maintenance therapy, the benefits of efficacy versus adverse effects of drug-related toxicity, and the interactions between antiretroviral drugs and ganciclovir or foscarnet. Dr. W. Lawrence Drew's career in this area has been long-standing and productive, and he is one of the leading experts in the field. In this update he addresses these perplexing issues. PMID- 1313314 TI - Absence of antibody to human spumaretrovirus in patients with chronic fatigue syndrome. PMID- 1313315 TI - The effect of norepinephrine on the coronary microcirculation. AB - The role of the sympathetic nervous system in the regulation of large coronary artery tone has been well defined. Studies of adrenergic regulation of coronary resistance vessels have largely been limited to indirect inferences based on flow measurement obtained in vivo. The purpose of the present study was to determine the effects of norepinephrine (NE) on the coronary microcirculation using direct in vitro approaches. Porcine coronary microvessels (80-200 microns in diameter) were pressurized in isolated organ chambers. Diameters were measured using a Halpern microvessel imaging apparatus. After preconstriction with leukotriene D4, NE caused complete relaxation. Relaxations to NE were inhibited by propranolol. Relaxations to NE were also inhibited by LY83583 (which depletes cGMP) and hemoglobin (which binds endothelium-derived relaxing factor, EDRF). NE caused minimal or no constriction in both preconstricted and nonpreconstricted microvessels even in the presence of hemoglobin and propranolol. In conclusion, NE predominantly dilates porcine coronary microvessels, both by beta-adrenoceptor activation and by stimulating release of EDRF. There is minimal alpha adrenoceptor-mediated constriction of coronary microvessels. PMID- 1313316 TI - Heterogeneity of postjunctional alpha 1-adrenoceptors in mammalian aortae: subclassification based on chlorethylclonidine, WB 4101 and nifedipine. AB - The effects of chlorethylclonidine, WB 4101 and nifedipine on norepinephrine induced contractions of rat, guinea-pig, rabbit and dog aortae were investigated in order to characterize the alpha 1-adrenoceptor subtype(s) present in the aortae of these different species. The putative alpha 1A-adrenoceptor antagonist, WB 4101, was significantly more potent in the rat aorta compared to the rabbit, guinea-pig and dog aortae which were not significantly different from each other. The calcium channel antagonist, nifedipine (1 microM), had little or no effect on norepinephrine-induced contractions in aortic segments from the rabbit, guinea pig and dog; whereas in the rat aorta, nifedipine significantly inhibited the response to norepinephrine. Based on the studies with WB 4101 and nifedipine, alpha 1-adrenoceptors in rat aorta would be tentatively classified as alpha 1A adrenoceptors, whereas those in the guinea-pig, rabbit and dog aortae would be of the alpha 1B-adrenoceptor subtype. The putative irreversible alpha 1B adrenoceptor antagonist, chlorethylclonidine, inhibited the response to norepinephrine in aortae from all species, but to dramatically different degrees. The response to norepinephrine was inhibited by 500-fold and 450-fold by chlorethylclonidine in the rat and dog aortae, respectively, whereas in the guinea-pig and rabbit aortae, the potency of norepinephrine was reduced by only 3 and 20-fold, respectively. Thus, based on studies with chlorethylclonidine, alpha 1-adrenoceptors in the rat and dog aortae would be classified as alpha 1B adrenoceptors (i.e., chlorethylclonidine-sensitive), whereas alpha 1A adrenoceptors (chlorethylclonidine-insensitive) would predominate in the guinea pig aorta, and possibly both alpha 1A- and alpha 1B-adrenoceptors would coexist in the rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313317 TI - Nursing care of the adult client with AIDS and cytomegalovirus infection. AB - Cytomegalovirus (CMV) is a pathogen causing major disease in an HIV-infected individual. This AIDS-related opportunistic infection results in severe morbidity from chorioretinitis, pneumonitis, encephalitis, adrenalitis, esophagitis, cholangitis, and hepatitis. The author provides a comprehensive overview of CMV infection as seen in adults with HIV disease and related nursing care, and discusses issues related to concerns about occupational exposure among healthcare workers. PMID- 1313318 TI - Acetate free biofiltration. Effects on peripheral blood monocyte activation and cytokine release. AB - Acetate free biofiltration (AFB), a new hemodiafiltration (HDF) technique characterized by a buffer free dialysate and postdilution infusion of a sterile HCO3 solution, was recently proposed as an alternative to HDF performed with acetate or bicarbonate dialysate. To evaluate the effects of dialysate buffer on immune cell activation, release of interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) from peripheral blood monocytes was studied in 12 uremic patients before and after HDF with polyacrylonitrile membranes (Filtral 12, Hospal Laboratories, Bologna, Italy) and consecutive dialysis with acetate, bicarbonate, and AFB. Data were correlated with the monocyte cytoplasmic concentration of Ca++, an index of early cell activation. Levels of bacterial endotoxins in the acetate, bicarbonate, buffer free dialysate, and infusate for AFB were also determined. Results showed that release of IL-1, PGE2, and LTB4, was greater after HDF with acetate than with bicarbonate; after bicarbonate dialysis, however, TNF production was significantly higher. On the other hand, after AFB, minimal production of these cytokines was seen and TNF, in particular, was undetectable. There was a direct correlation between release of cytokines in the monocytes and cytoplasmic Ca++ content. In the bicarbonate dialysate, detectable levels of bacterial endotoxins were found, whereas the acetate, buffer free dialysate, and infusate were endotoxin free. It was concluded that acetate dialysis directly activates peripheral blood monocytes to produce IL-1, PGE2, and LTB4, whereas bicarbonate induced TNF activation occurs through endotoxins. In AFB, which uses a buffer free dialysate and sterile bicarbonate infusion, monocyte activation is negligible. PMID- 1313319 TI - Psychiatric disturbances associated with ganciclovir therapy. AB - OBJECTIVE: To report a case of possible ganciclovir-induced psychiatric disturbances. CASE SUMMARY: A patient with AIDS who had no known psychiatric history and mild renal dysfunction experienced exacerbation of cytomegalovirus retinitis and was treated with ganciclovir 5 mg/kg iv q12h. The patient complained of nightmares and developed visual hallucinations and severe agitation on day 15 of ganciclovir therapy. The problems resolved after haloperidol administration and ganciclovir withdrawal and reappeared when the same regimen was reinstituted. However, the patient was able to tolerate the maintenance dose of ganciclovir at 5 mg/kg/d along with haloperidol later without further episodes of visual hallucinations. DISCUSSION: Case reports in the literature on ganciclovir-or its analog, acyclovir-, induced psychiatric disturbances were reviewed and compared. The potential relationship between ganciclovir accumulation in patients with renal insufficiency and the observed central nervous system problems in our patient was postulated. CONCLUSIONS: It is likely that ganciclovir accumulation contributed to the acute psychotic episodes observed in our patient. Adjusting ganciclovir dosage based on the patient's renal function is probably the only approach required to prevent or reduce the incidence of these episodes. PMID- 1313320 TI - Enalapril to lisinopril: economic impact of a voluntary angiotensin-converting enzyme-inhibitor substitution program in a staff-model health maintenance organization. AB - OBJECTIVE: The cost-effectiveness of a voluntary program that switched enalapril to lisinopril therapy in patients with benign essential hypertension in a staff model health maintenance organization (HMO) was evaluated. DESIGN: The one-year nonrandomized, controlled trial was performed from November 1989 through October 1990. PARTICIPANTS: One hundred twenty-seven patients were entered into the study: 75 who converted from enalapril to lisinopril and 52 who remained on enalapril throughout the study period. Patients were excluded from analysis because of diagnosis (not benign essential hypertension) or insufficient data collection. INTERVENTIONS: Patients taking enalapril were asked by staff pharmacists if they were willing to consider switching from enalapril to lisinopril. To encourage patients, the HMO agreed to waive the drug rider copayment for three months. If patients were willing, their physicians were contacted and they established the lisinopril dosage. MAIN OUTCOME MEASURES: Total direct cost and savings resulting from converting patients from enalapril to lisinopril were measured and compared with costs of therapy for patients who remained on enalapril. RESULTS: The control and study groups were evenly matched according to demographics and concomitant drug therapy. Drug acquisition costs, costs associated with waiving drug rider copayment, pharmacy administrative costs, costs of managing adverse events, costs of visits to physicians, and laboratory test costs were assessed. Depending on the cost of capital assumed, net savings ranged from $85 to $110 per patient converted from enalapril to lisinopril. Monthly net savings that ranged from $2.04 to $2.61 per patient were required to result in overall net savings within the first two years. CONCLUSIONS: In a regular practice setting, a net savings is realized in less than 12 months when patients are converted from enalapril to lisinopril for treatment of benign essential hypertension. The voluntary therapeutic interchange program provided a good means for achieving cost controls for pharmacy expenses. PMID- 1313321 TI - Changes in criminal activity after entering methadone maintenance. AB - The impact of different approaches to methadone maintenance on the level of crime committed by heroin addicts was examined in a cohort of addicts entering methadone treatment. The cohort comprises three groups: 72 subjects (group 1) who were approved for treatment and referred to a long-term programme which tolerated continued illicit drug use in treatment; 159 subjects (group 2) who were referred to an abstinence orientated programme from which clients who continued to use heroin were expelled; and 84 subjects who were rejected as unsuitable or failed to complete the assessment process. Official records of convictions were used to calculate conviction rates in the pre- and post-assessment periods. Differences between groups in conviction rates for drug and property crimes were analysed using Poisson regression. Three variables--age, sex and age of first criminal conviction--were significant predictors of conviction rates and all analyses controlled for these variables. Most of the rejected subjects entered treatment during the study period and it was, therefore, not possible to interpret differences between treated and untreated subjects. Among those who entered treatment, property offence rates actually rose, due to a significant increase in conviction rates in group 2. Subjects in group 1 were retained significantly longer in treatment than those in group 2. Among those who remained in treatment less than 12 months, most offences occurred after leaving treatment. When conviction rates were adjusted for time spent in treatment, the differences between the clinics disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313322 TI - Signal transduction in glycosaminoglycan (GAG) synthesis by cultured chondrocytes and its inhibition by inflammatory cell-derived hydrogen peroxide. AB - Signal transduction in glycosaminoglycan (GAG) synthesis by chondrocytes has been studied. The activity of various subspecies of protein kinase C (PKC) in chondrocytes derived from rodent costal cartilage and bovine articular cartilage has been determined and the role of PKC in GAG synthesis as well as the possible interactions of PKC with calcium- or cyclic AMP (cAMP)-dependent systems in the synthesis of GAG. To investigate GAG synthesis in inflammatory conditions, the effects of hydrogen peroxide on PKC activity of the chondrocytes and PKC-mediated GAG synthesis have been studied. 12-O-Tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, increased GAG synthesis in a dose-dependent fashion. This suggests that PKC up-regulates the synthesis of GAG in cultured chondrocytes. This increase was not significantly affected by simultaneous addition of the calcium ionophore, ionomycin, or dibutyryl cAMP (db-cAMP), a cAMP analogue. Ionomycin and db-cAMP, when used alone, did not significantly alter GAG synthesis by chondrocytes. Thus there appears to be no interaction between PKC and calcium- or cAMP-mediated systems in GAG synthesis. The increase in GAG synthesis induced by TPA was significantly (P less than 0.01) reduced by simultaneous addition of hydrogen peroxide (10(-6) M), without affecting cell viability. The activity of PKC in chondrocytes pretreated with 10(-6) M hydrogen peroxide was also significantly inhibited. Thus hydrogen peroxide which is generated by inflammatory cells may be important in suppression of GAG synthesis in inflammatory conditions. PMID- 1313323 TI - Staphylococcal infection of hidradenitis excisions. PMID- 1313324 TI - Partial hepatic resection under intermittent hepatic inflow occlusion in patients with chronic liver disease. AB - A partial hepatic resection was performed in 13 patients with chronic liver disease using intermittent hepatic inflow occlusion. Eleven patients had liver cirrhosis and two had chronic hepatitis. Seven patients were classified as Child's grade A and six as Child's grade B before operation. Dissection of the hepatic parenchyma was performed during intermittent inflow occlusion. The time of clamping and declamping was 10-20 min and 5-8 min, respectively. Postoperative data on liver function showed recovery to preoperative levels by about 10 days after operation. There were no life-threatening complications. These results indicate that intermittent hepatic inflow occlusion can be achieved easily and safely to allow non-anatomical resection in patients with chronic liver disease. PMID- 1313325 TI - Lymph node metastasis from early gastric cancer: endoscopic resection of tumour. AB - The clinicopathological features of 748 solitary early gastric cancers were examined with regard to lymph node metastasis. Among several factors, only depth of invasion and tumour size correlated significantly with node involvement. Tumours which satisfy the following criteria may not metastasize to lymph nodes: (1) confined to the mucosa; (2) less than 1.5 cm in diameter; (3) macroscopically elevated; (4) macroscopically depressed, without intramural ulcers or ulcer scars (endoscopically, no fold convergence); and (5) histologically differentiated. With a recently developed endoscopic technique small gastric tumours can safely be resected. The cut margin and depth of tumour invasion can be verified histologically in the specimen. If an endoscopically removed tumour satisfies the above criteria, further surgical intervention may be optional as the outcome of endoscopic resection is comparable to that of radical surgery in the absence of node involvement. PMID- 1313327 TI - Benign lesions of the mandibular and maxillary region in children: characterization by CT and MRI. AB - The CT criteria for classifying lesions of the mandibular and maxillary regions in adults as benign or malignant are well recognized: irregular soft tissue margins and bone destruction. We reviewed the charts of 12 pediatric patients from 3 institutions to evaluate these criteria in children. These masses were evaluated by CT and/or MRI based solely on well-recognized and published criteria. The patients' ages ranged from 4 mo to 18 yr. The histological diagnoses were ameloblastoma (4), hemangioma (2), lymphangioma, desmoplastic fibroma, hemangiopericytoma, neurofibroma, fibrous dysplasia, and juvenile angiofibroma. All but one case was surgically proven. Among the 12 cases, 5 had bone destruction and 5 showed irregular soft tissue margins. Three cases satisfied both criteria. With well-recognized CT criteria (in adult patients), characterization of these processes led to an incorrect diagnosis of a malignant lesion in 8 of the 12 cases preoperatively. Therefore, CT and MR imaging should only be a guide to the planning and extent of surgical resection. Without clearly defined distal spread of the mass, the classification of these masses in children should be made with caution. PMID- 1313326 TI - Prevalence of bloodborne infective agents among people admitted to a Canadian hospital. AB - OBJECTIVE: To determine the prevalence rates of hepatitis B surface antigen (HBsAg) and antibodies to the human immunodeficiency virus (anti-HIV) and the hepatitis C virus (anti-HCV) among people admitted to an urban Canadian hospital. DESIGN: Anonymous unlinked serosurvey. SETTING: A 420-bed teaching hospital in Toronto. PARTICIPANTS: All 3000 patients admitted to the hospital on weekdays from January to June 1990. An attempt was made to exclude those who were readmitted during the study period. INTERVENTIONS: Serum samples from all the patients were tested for HBsAg and anti-HIV, and 1306 samples were also tested for anti-HCV by means of enzyme immunosorbent assays; reactions were confirmed by means of specific antibody neutralization or immunoblot assay. MAIN RESULTS: The prevalence rates of HBsAg, anti-HIV and anti-HCV were 2.1% (95% confidence interval [CI] 1.6% to 2.6%), 0.6% (95% CI 0.3% to 0.9%) and 0.5% (95% CI 0.1% to 0.9%) respectively. CONCLUSIONS: This is the first report defining rates of infection with these bloodborne agents among patients admitted to a Canadian hospital. The observed rates likely reflect the patient population served by our hospital and do not necessarily apply to other Canadian centres. The results support the use of universal precautions in health care settings. PMID- 1313328 TI - CT demonstration of pelvic wall spread in primary colonic linitis plastica. AB - Primary linitis plastica of the colon is a rare entity, and its radiographic and CT findings have been described in previously published literature. We present the CT demonstration of the pelvic wall spread in this unusual disease, and briefly review its radiologic and pathologic features. PMID- 1313329 TI - Cytogenetic analysis of 39 pediatric central nervous system tumors. AB - Consistent cytogenetic abnormalities have been described in many pediatric solid tumors, including Ewing's sarcoma, Wilms' tumor, and neuroblastoma. Similar analysis of pediatric central nervous system (CNS) tumors has been hampered by technical problems. We report chromosome results from 39 pediatric CNS tumors. Abnormalities of chromosome 17 were noted in 3 of 11 primitive neuroectodermal tumors (including i(17q) in 2 tumors), confirming data observed by other investigators. Cells from 2 of 11 primitive neuroectodermal tumors (PNET) exhibited loss or structural abnormalities involving chromosome 11. Loss or distal deletion of chromosome 7q was noted in cells from two PNETs. Because other investigators have shown loss of heterozygosity on 17p in about one-third of PNET, we propose that chromosome regions 7q and 11 are areas worthy of further study in pediatric PNET. Numerical abnormalities were noted in 6 of 21 astrocytomas. Hyperdiploidy was demonstrated in 1 of 4 pilocytic astrocytomas and pseudopolyploidy was demonstrated in 4 of 13 anaplastic astrocytomas. Structural chromosome abnormalities (translocations, deletions) were noted in 4 of 13 anaplastic astrocytomas. Complex structural anomalies were observed in one craniopharyngioma. A rhabdoid tumor of the brain exhibited multiple complex structural rearrangements but did not exhibit the monosomy 22 observed in some rhabdoid tumors. Hypodiploidy and loss of chromosome 22 were noted in a clinically aggressive meningioma, corroborating observations by other investigators. PMID- 1313330 TI - Cytogenetic findings in a malignant fibrous histiocytoma of the gallbladder. AB - We report the cytogenetic findings in a rare tumor, a malignant fibrous histiocytoma of the gallbladder. Four related clones, two near-diploid and two near-tetraploid, which appeared to have been formed by a doubling of the near diploid clones, were present. Numerous structural and numerical abnormalities characterized the tumor. Structural rearrangements included reciprocal translocations, translocations of unidentified material onto chromosomes, and deletions. Chromosomes involved in the rearrangements included 1, 3, 10, 12, 14, 16, and 19. Numerical changes included trisomy of chromosomes 2, 8, 10, and 20. Double minute chromatin bodies ranging in number from 5 to several were present in over a third of the cells. PMID- 1313331 TI - Frequent deletions in nine newly immortal human cell lines. AB - Nine newly immortal lines of human fibroblasts transfected with SV40 T antigen were examined for recurrent chromosome losses. In order of decreasing frequency, all nine lines had three or more of the following minimal deletions specifically associated with the immortalization event: del(6)(q21), del(3)(p24), del(1)(p34), del(4)(p25), del(5)(p14), del(11)(p11), del(11)(q14), del(12)(p12), and del(14)(p?). Many other chromosome changes were not clearly associated with immortalization, but were acquired during other stages of this multistep model of neoplastic transformation. We propose that these chromosome loci associated with immortalization are candidates for the location of genes involved in cellular senescence. PMID- 1313332 TI - HIV-1 infectivity of human carcinoma cell lines lacking CD4 receptors. AB - Human immunodeficiency virus type 1 (HIV-1) prototype, HIV1 LAV, and a Zairian virus HIV1 NDK, an isolate highly cytopathic for CD4+ lymphocytes, were used to infect eleven different CD4 negative non-lymphoid human cell lines. Eight of the lines were derived from carcinomas wherein human papillomavirus was thought to have been etiologic. All these cell lines lacked CD4 receptor and CD4 specific mRNA. After cocultivation with sensitive CEM cells, HIV-1 LAV was rescued from six infected cell lines and HIV-1 NDK from nine. Shedding of free virus into the culture medium was observed in three cell lines infected by HIV-1 NDK and in only one cell line infected by HIV-1 LAV. The infectibility of CD4 negative cell lines indicates that both HIV-1 strains were able to use a CD4 independent mechanism to infect the cells; however, HIV-1 NDK showed the higher efficiency of infection. This virus was also able to overcome the intracellular block of viral reproduction. These results suggest that a broader spectrum of cell types of non lymphoid origin lacking the CD4 receptor can serve as a viral reservoir. In some cases they are direct producers of infectious HIV-1 particles. This suggests, that in addition to immunosuppressive mechanisms, HIV-1 could play a more direct role in induction of neoplastic changes. PMID- 1313333 TI - Peroxidase oxidizes N-nitrosomethylaniline to ultimate carcinogens(s) binding to DNA and transfer RNA in vitro. AB - Carcinogenic N-nitrosomethylaniline is oxidized in vitro by horseradish peroxidase in the presence of H2O2 to ultimate carcinogens, which bind to DNA and transfer RNA (tRNA). tRNA is more accessible for modification by the activated carcinogen studied. The modification of nucleic acid by N-nitrosomethylaniline metabolite(s) formed by peroxidase is inhibited by some compounds of physiological importance (ascorbate, glutathine) and by radical trapping agents (nitrosobenzene, methyl viologen). 32P-postlabeling assay of DNA and tRNA modified by N-nitrosomethylaniline activated by peroxidase shows covalent adduct formation with nucleic acids. The role of peroxidases in the activation of N nitrosamines leading to organ and/or cell specificity of these carcinogens is discussed. PMID- 1313334 TI - Monoclonal antibody MON-114: detection of a marker for neuroendocrine differentiation in human lung cancer. AB - Mouse monoclonal antibody MON-114 was generated upon immunization with a human small cell lung carcinoma cell line GLC-19. Immunohistochemical analysis of normal tissues with MON-114 showed staining of the adrenal gland, brain and peripheral nerves. With respect to human lung carcinomas, 7 out of 8 small cell lung carcinomas were positively stained as well as 5 out of 5 carcinoid tumors, whereas only 4 out of 31 squamous cell carcinomas and 3 out of 19 adenocarcinomas were weakly stained. Furthermore, 1 large cell carcinoma was negative for MON-114 staining. Apparently, MON-114 stains cells of neuroendocrine differentiation. PMID- 1313335 TI - P element transposition in vitro proceeds by a cut-and-paste mechanism and uses GTP as a cofactor. AB - We have developed an in vitro reaction system for Drosophila P element transposition. Transposition products were recovered by selection in E. coli, and contained simple P element insertions flanked by 8 bp target site duplications as observed in vivo. Transposition required Mg+2 and partially purified P element transposase. Unlike other DNA rearrangement reactions, P element transposition in vitro used GTP as a cofactor; deoxyGTP, dideoxyGTP, or the nonhydrolyzable GTP analogs GMP-PNP or GMP-PCP were also used. Transposon DNA molecules cleaved at the P element termini were able to transpose, but those lacking 3'-hydroxyl groups were inactive. These biochemical data are consistent with genetic data suggesting that P element transposition occurs via a "cut-and-paste" mechanism. PMID- 1313336 TI - V(D)J recombination in mouse thymocytes: double-strand breaks near T cell receptor delta rearrangement signals. AB - In the murine T cell receptor delta locus, V(D)J recombination events frequently involve the D2 and J1 elements. Here we report the presence of double-strand breaks at recombination signals flanking D2 in approximately 2% of thymus DNA. An excised linear species containing the sequences between D2 and J1 and a circular product of the joining of D2 and J1 recombination signals were also found. Although broken molecules with signal ends were detected, no species with coding ends could be identified. Observation of these broken molecules in thymus, but not in liver or spleen, provides the first direct evidence for an association between specific cleavage of chromosomal DNA and recombination in mammalian cells, and supports a breakage-reunion model of V(D)J recombination. PMID- 1313337 TI - A transgene target for positional regulators marks early rostrocaudal specification of myogenic lineages. AB - In transgenic mice, muscle-specific regulatory elements from the myosin light chain (MLC) 1/3 locus drive graded expression of a linked CAT reporter gene in selected fast muscles along the anteroposterior axis of the adult animal. The gradient of MLC-CAT transcripts is established early in development, during the generation of somites from the paraxial mesoderm and the activation of myogenic factor gene expression, and is not reflected in the expression of the endogenous MLC1 gene. At later embryonic stages, the gradient of MLC-CAT transcripts persists in intercostal and intervertebral muscles, but is not maintained in other axial muscles. Profiles of CAT transgene activity reveal that the gradient is generated during the maturation of increasingly caudal somites, opposite to the direction of somite development, and is retained in dissociated somite cultures. We propose that coexpression of myogenic factors is necessary but not sufficient to regulate expression of the MLC-CAT transgene, which is responsive to additional positional cues in the embryo. PMID- 1313338 TI - Involvement of major histocompatibility complex class II antigen in Epstein-Barr virus-mediated B cell proliferation. AB - Five MHC class II monoclonal antibodies costimulated proliferation of cord blood leukocytes with Epstein-Barr virus. These agonistic antibodies were of different isotypes, but all of them were either specific for or cross-reacting with HLA-DR. The other MHC class II antibodies, including three that were specific for HLA-DQ and one that was specific for HLA-DP and also those that were specific for MHC class I or leukocyte common antigen, were not costimulatory. The agonistic effect of different MHC class II antibodies was additive, such that costimulation by different antibodies combined significantly exceeded that achieved by either of these antibodies alone. Spent culture media of B cell lines also costimulated B cell proliferation with the virus. Although MHC class II antibodies augmented the effects of suboptimal concentration of the conditioned media, their combined effects did not exceed the maximum costimulation achieved by either the antibodies or the spent culture media alone. These results raised the possibility that MHC class II antigen may contain distinct functional domains involved in the regulation of B cell progression. PMID- 1313339 TI - Expression and combinatorial diversity of germ line-encoded T cell receptor V genes in human peripheral blood T cells. AB - The potential diversity of the T cell receptor (TcR) is defined by the combinational expression of variable segments and by mechanisms that insert or delete nucleotides at the junctional regions. The available repertoire is strongly influenced by negative and positive selection events. To study whether the diversity of the human T cell receptor of peripheral T cells is further restricted by the interaction between the TcR alpha and beta chains, we compared the level of transcription of different V alpha elements in human T cell blasts expressing either restricted or unrestricted sets of V beta genes. Our data establish that in some individuals, but not in others, the transcription of a given V alpha element is independent from the presence of particular V beta transcripts. Furthermore, our data also suggest that, in contrast to mouse, major TcR V gene deletions are absent in humans. Taken collectively, these results indicate that the diversity of the peripheral human TcR repertoire can benefit from the combinatorial expression of all the V elements present in the genome. PMID- 1313340 TI - Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (Fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. A dose-ranging study. AB - BACKGROUND: We compared the efficacy and safety of different dosages of a low molecular-weight heparin, CY 216 D (Fraxiparine), in the treatment of submassive pulmonary embolism with unfractionated heparin in a prospective, randomized, dose finding study. METHODS AND RESULTS: The primary outcome was the evolution of pulmonary vascular obstruction. We enrolled 101 patients. Four patient groups were formed: standard heparin by continuous intravenous infusion (group 1) and Fraxiparine subcutaneously 400, 600, and 900 anti-Xa Institute Choay units/kg, respectively (groups 2, 3, and 4). Inclusions were stopped prematurely in groups 3 and 4 because of the incidence of major bleedings. At day 8, the improvement of the pulmonary vascular obstruction and the major bleedings were similar in groups 1 and 2. CONCLUSIONS: The Fraxiparine dosage of 400 anti-Xa Institute Choay units/kg is as effective and safe as unfractionated heparin in the treatment of submassive pulmonary embolism. PMID- 1313341 TI - Collagen loss in the stunned myocardium. AB - BACKGROUND: This study was performed to biochemically assess and quantify the previously observed ultrastructural alterations in the collagen matrix of stunned myocardium. METHODS AND RESULTS: The stunned myocardium was produced in 13 mongrel dogs by a series of 12 coronary artery occlusions of 5 minutes followed by 10-minute reperfusion periods, with a final reperfusion period of 90 minutes. Regional systolic function in the stunned myocardium was 17% of control. Relative end-diastolic length in the stunned region increased up to 8%. There was a nonuniform transmural loss of collagen. Hydroxyproline in the stunned endocardium was not different from control. The stunned midwall and epicardium demonstrated 12.5% (p less than 0.05) and 14.6% (p less than 0.005) decreases, respectively. All transmural layers in the stunned myocardium had significant increases in collagenase activity before procollagenase activation, averaging a 73.6% increase (p less than 0.025). Complete activation of all procollagenase forms with aminophenylmercuric acetate revealed no differences in fully activated collagenase between the stunned and normal regions. The lysosomal enzymes, elastase and cathepsin G, were not different between stunned and normal zone tissue. These results would tend to exclude exogenous sources of protease in the stunned myocardium at the 90-minute final reperfusion time frame. Collagen fibers were isolated from the stunned and normal zone tissue and underwent dansyl chloride reaction. Stunned collagen fibers had 9% greater dansyl labeling, suggesting greater numbers of exposed N-terminal amino acid residues on the fiber and compatible with greater enzymatic cleavage activity on the stunned collagen matrix. Tissue water content was consistently greater in the stunned region compared to the normal: a uniform transmural increase of approximately 1.7%. CONCLUSIONS: The stunned myocardium is characterized by both systolic dysfunction and diastolic expansion or dilatation. Endogenous procollagenase is activated by the ischemic process leading to degradation of the extracellular matrix. The underlying mechanisms may be relevant in ischemic enlargement of the heart and cardiomyopathy. PMID- 1313342 TI - Divergent kinetics of 201Tl and 99mTc-SESTAMIBI in cultured chick ventricular myocytes during ATP depletion. AB - BACKGROUND: Thallous chloride (201Tl) and hexakis(2-methoxyisobutyl isonitrile) technetium (I) (99mTc-SESTAMIBI) are myocardial perfusion imaging agents with biological properties that also reflect tissue viability. Initial myocellular uptake rates of 201Tl reflect activity of Na,K-ATPase, whereas those of 99mTc SESTAMIBI reflect mean plasma membrane potential. METHODS AND RESULTS: To better understand the mechanistic responses of these tracers to myocellular injury, cultured chick embryo cardiac myocytes were metabolically inhibited in iodoacetate (1 mM) and rotenone (10 microM) for up to 2 hours, and initial uptake rates of each agent were determined at successive intervals along with correlative cellular contents of ATP, sodium, and potassium and lactate dehydrogenase release. ATP content fell from 30.5 +/- 1.4 to 2.7 +/- 0.9 nmol.(mg protein)-1 within 2 minutes, whereas sodium and potassium contents ran down their thermodynamic gradients more slowly (t 1/2 approximately 60 minutes). Modestly severe cell injury was produced at 2 hours as estimated by lactate dehydrogenase release (18% of total). Initial uptake rates of 201Tl declined from 6.9 +/- 0.8 to 4.0 +/- 0.4 fmol.(mg protein)-1.(nMo)-1.(min)-1 by 20 minutes and remained depressed and ouabain (100 microM)-insensitive at 30 +/- 13% of control. Conversely, initial uptake rates of 99mTc-SESTAMIBI increased from 10.6 +/- 0.8 to 15.0 +/- 0.6 fmol.(mg protein)-1.(nMo)-1.(min)-1 within 10 minutes, remained elevated for 40-60 minutes, and later declined to low values. Injury-induced enhancement of initial uptake rates of 99mTc-SESTAMIBI were insensitive to ouabain (100 microM), carbonyl cyanide-m-chlorophenyl hydrazone (5 microM), and valinomycin (1 microgram/ml) but were significantly inhibited by 130 mM Ko buffer, Ba2+ (1 mM), glybenclamide (100 microM), and quinacrine (10 microM). CONCLUSIONS: Uptake rates of 201Tl monotonically decline, correlating with Na-K pump inhibition from ATP depletion. Conversely, uptake rates of 99mTc-SESTAMIBI at first increase above control for 40-60 minutes, indicating a mean plasma membrane hyperpolarization possibly resulting from opening of ATP-sensitive and arachidonic acid-activated potassium channels, before declining to low values with more severe cell injury. Correlative non-flow-dependent relations between 201Tl and 99mTc-SESTAMIBI contain information regarding the degree of myocellular injury. PMID- 1313343 TI - Inhibition of cellular proliferation after experimental balloon angioplasty by low-molecular-weight heparin. AB - BACKGROUND: The proliferative response induced by balloon angioplasty is known to be an important factor in the development of restenosis after successful coronary angioplasty. METHODS AND RESULTS: To study the effects of low-molecular-weight heparin (LMWH) on cellular proliferation after experimental balloon angioplasty, LMWH (3.9 kd, 400 anti-Xa units/kg/day) was given to 20 male New Zealand White rabbits. After an intimal fibromuscular plaque was induced by electrical stimulation in the right carotid artery, LMWH was applied during the 7 days after balloon dilatation. As the control group, 20 other rabbits underwent balloon angioplasty without application of LMWH. The vessels were excised 3, 7, 14, and 28 days after balloon treatment. During the final 18 hours before the rabbits were killed, bromodeoxyuridine was applied. Intimal wall thickness increased from 13 +/- 5 cell layers (preangioplasty control group) to 20 +/- 6 cell layers in the LMWH-treated group at 28 days (p less than 0.05). In contrast, histological examination of control animals 28 days after angioplasty revealed a significant increase to 35 +/- 15 cell layers (p less than 0.01). Immunohistological quantification showed a significant increase (p less than 0.001) of cells undergoing DNA synthesis at 3 (10.2 +/- 4.2%) and 7 (7.7 +/- 4.8%) days after balloon dilatation in control animals. In contrast, at 3 and 7 days after balloon treatment, the percentage of cells undergoing DNA synthesis in LMWH-treated rabbits was lower (3 days, 2.7 +/- 1.8%; 7 days, 1.9 +/- 0.3%) than the corresponding untreated controls but showed a significant increase (p less than 0.01) compared with the preangioplasty controls. The differences between the two groups were statistically significant, however (3 days, p less than 0.01; 7 days, p less than 0.05). As early as 14 days after angioplasty, the extent of cellular proliferation was normalized and was comparable to the preintervention levels in both groups. CONCLUSIONS: Our data indicate that the proliferative response after balloon angioplasty can be reduced in vivo by early treatment with LMWH and thus encourage further clinical investigations. PMID- 1313344 TI - Endogenous adenosine blunts beta-adrenoceptor-mediated inotropic response in hypoperfused canine myocardium. AB - BACKGROUND: Adenosine attenuates beta-adrenoceptor-mediated inotropic responses through GTP-binding protein in vitro. The goal of the present study was to test the hypothesis that endogenous adenosine released from the ischemic myocardium blunts the inotropic response to beta-adrenergic stimulation. METHODS AND RESULTS: In 45 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Coronary perfusion pressure was reduced so that coronary blood flow was decreased to 60% of the basal level by partial occlusion of the bypass tube, and the reduced coronary perfusion pressure was kept constant thereafter. Inotropic responses to isoproterenol were assessed by fractional shortening of the myocardium in the perfused area. After the onset of hypoperfusion, lactate extraction ratio (18.8 +/- 1.2%) and fractional shortening (20.7 +/- 1.1%) were significantly decreased to -8.4 +/- 8.0% and 5.9 +/- 1.5%, respectively, and coronary arteriovenous differences of adenosine were increased from 4.6 +/- 3.6 to 89.4 +/- 10.5 pmol/ml. In the untreated condition, an intravenous infusion of isoproterenol (150 ng/kg/min) augmented fractional shortening from 5.9 +/- 1.5% to 13.6 +/- 0.8%. When adenosine release was attenuated by administration of prazosin (4 micrograms/kg/min i.c.) during hypoperfusion, the response of fractional shortening to isoproterenol (from 5.3 +/- 1.2% to 20.5 +/- 1.4%) was much greater (p less than 0.05) than that in the untreated control condition. Exogenous administration of adenosine significantly attenuated the inotropic response to isoproterenol in the prazosin-treated hearts. In contrast, an adenosine receptor antagonist, 8-phenyltheophylline, also enhanced the inotropic response to isoproterenol. The attenuation of beta-adrenoceptor-mediated inotropic response by adenosine could not be attributed to the inhibition of norepinephrine release from the sympathetic nerve endings, because identical results were observed in the chemically denervated hearts. CONCLUSIONS: Endogenous adenosine released from the ischemic myocardium attenuates beta-adrenoceptor-mediated inotropic response in the ischemic heart. PMID- 1313345 TI - The urge to prevent restenosis after percutaneous transluminal coronary angioplasty. Scylla and Charybdis in disguise. PMID- 1313346 TI - Magnetic resonance behaviour of lipiodol. AB - Lipiodol is a frequently used contrast agent for lymphangiography and more recently has been used in the investigation of hepatoma. We describe the magnetic resonance characteristics of lipiodol using a Siemens 1.5 T Magnetom with reference to the appearance and behaviour of lipiodol in abdominal lymphadenopathy. The characteristics described differ from previously published reports. PMID- 1313347 TI - Developmental expression of defensive responses during exposure to conspecific adults in preweanling rats (Rattus norvegicus). AB - I examined preweanling rats' (Rattus norvegicus) expression of ultrasounds and secretion of ACTH when exposed to unfamiliar adult male rats or to their mothers. Pups at 7 days of age produced similar levels of ultrasonic vocalization near both unfamiliar males and mothers. However, these pups could discriminate familiar from unfamiliar adults because ACTH was significantly higher in pups near adult males than in those near mothers. At 14 days of age, pups avoided adult males but not their mothers; therefore, adult males represented a significant threat. Importantly, 14-day-old rats significantly reduced ultrasound production only when near adult males. Pups at 21 days of age no longer emitted ultrasounds when socially isolated or when near conspecific adults. In addition, 14- and 21-day-old rats produced similar elevated ACTH levels across stimulus conditions. Results show significant changes in preweanling rats' responses to conspecific adults. PMID- 1313348 TI - Long-term sequelae after recovery from cytomegalovirus pneumonia in allogeneic bone marrow transplant recipients. AB - The clinical course of cytomegalovirus (CMV) pneumonia in seven consecutive bone marrow transplant (BMT) recipients during a 24-month period was studied. Retrospective analysis of clinical data on the recipients with CMV pneumonia during the illness and prospective follow-up of those who recovered from the pneumonia was performed. Those who had CMV as the sole pathogen and with lymphocytosis in the BAL or the peripheral blood during the illness recovered from the pneumonia. On the contrary, those who had mixed bacterial or fungal infection with peripheral lymphopenia died. Persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, was observed in the survivors. Two subsequently developed restrictive lung disease and two had relapse of their primary malignancy. These data suggest that CMV pneumonia in BMT patients is associated with significant long-term sequelae. The phenomenon of persistent lymphocytosis in the BAL and the peripheral blood, in the absence of CMV infection, supports Grundy's hypothesis that CMV pneumonia in BMT recipients is an immunopathologic condition. PMID- 1313349 TI - The effect of surgical treatment on survival from early lung cancer. Implications for screening. AB - We assessed the effect of surgery on survival from stage I non-small-cell lung cancer based on data collected in these screening programs. The majority of patients diagnosed in each program were treated by surgical resection, but 5 percent of the Sloan-Kettering group, 21 percent of the Hopkins group and 11 percent of the Mayo group failed to receive surgical treatment. Approximately 70 percent of the stage I patients in each program who were treated surgically survived more than five years, but there were only two five-year survivors among those who did not have surgery. We conclude that patients with lung cancers detected in stage I by chest x-ray film and treated surgically have a good chance of remaining free of disease for many years. Those stage I lung cancers which are not resected progress and lead to death within five years. Therefore, every effort should be made to detect and treat lung cancer early in high-risk populations. PMID- 1313350 TI - Advances in treatment of loco-regionally advanced lung cancer and the ACCP. A common ground. PMID- 1313351 TI - Postoperative respiratory failure secondary to Pneumocystis carinii pneumonia. AB - Pneumocystis carinii pneumonia (PCP) occurs frequently in individuals infected with the HIV virus. Malignancy, immunosuppressive drugs, and congenital immune deficiency may be associated with PCP. We describe a patient with stage 1 testicular carcinoma who developed hypoxemic respiratory failure two days after retroperitoneal lymph node dissection. Pneumocystis carinii organisms were demonstrated by catheter lavage samples and confirmed on bronchoalveolar lavage. Testing for HIV antibody by ELISA and the Western blot test were negative; HIV viral culture and polymerase chain reaction were also negative. Pneumocystis carinii pneumonia is unusual in localized surgically cured malignancies without obvious immunodeficiency and, to our knowledge, has not been described as a cause of postoperative respiratory failure. PMID- 1313352 TI - Prolonged partial remission of malignant fibrous histiocytoma in posterior mediastinum by immunotherapy. AB - The case of a 16-year-old female patient with the giant cell type of malignant fibrous histiocytoma (MFH) in the left posterior mediastinum is reported. This is a very unusual site for MFH. Immunotherapy induced a prolonged partial remission lasting 15 months with a marked reduction in tumor size. The usefulness of immunotherapy for MFH needs to be evaluated. PMID- 1313353 TI - Influence of beta-adrenergic receptor function during terbutaline treatment on allergen sensitivity and bronchodilator response to terbutaline in asthmatic subjects. AB - Nine asthmatic patients with an allergy to birch or timothy underwent bronchial allergen provocations on three different trial days, with intervals of 2 to 5 wk. Two weeks prior to one of the provocations, no medication was allowed. Before the other two provocations the patients had been on continuous treatment with oral terbutaline (7.5-mg slow-release pill bid) for 2 wk, which was discontinued 12 or 48 h before the allergen provocation. After allergen challenges, terbutaline was inhaled in increasing doses (0.5 mg, 1.0 mg, and 2.0 mg), and pulmonary function was measured after each dose. Before each allergen provocation, blood samples were drawn for measurements of catecholamine and terbutaline concentrations and for in vitro measurements of beta-adrenergic receptor function on lymphocytes (isoproterenol-induced accumulation of cyclic AMP). Beta-adrenergic receptor function on blood lymphocytes was impaired after the two treatment periods, compared with the drug-free period, and was significantly more depressed at 12 h than 48 h after dosing. The bronchial responsiveness to allergen, defined as PC20PEF (median values), was 1,700 biologic units (BU) after the period of no treatment and 220 BU and 445 BU at 12 and 48 h after discontinuation of the terbutaline treatment (p less than 0.1 after 48 h). Five of the nine patients exhibited increased bronchial responsiveness 48 h after treatment, compared to results without treatment. The responsiveness was similar on all occasions in three patients. The bronchodilator response to inhaled terbutaline after allergen induced bronchoconstriction was attenuated (p less than 0.01) at both 12 and 48 h after terbutaline, compared to results without treatment, indicating desensitization also of the bronchial beta-adrenergic receptors. We conclude that the early bronchial responsiveness to allergen is increased following a period of continuous treatment with a beta-adrenergic receptor agonist in some asthmatic patients and that the capability of a beta-agonist to reverse allergen-induced bronchoconstriction is attenuated after beta-agonist treatment. PMID- 1313354 TI - Evaluation of motor unit firing rates by standard concentric needle electromyography. AB - Motor unit firing rates at slight voluntary contraction were studied by standard concentric needle electromyography. Employing digital signal analysis techniques firing rates of motor units (MU) could be evaluated as long as four or less different MUs were activated in the vicinity of the concentric needle electrode. The extension of the recording area is defined by the recording properties of the electrode and the upper limit of rise-time for all MUPs being evaluated. Distant MUs, generating volume conducted potentials with rise-times greater than 0.8 ms, were excluded. In biceps muscles of 15 healthy controls the firing rate of the MU activated first was evaluated at that moment, when a second MU was recruited and was found to be 12.1 +/- 2.1 Hz (mean +/- S.D., n = 40). The firing rate of the fastest MU out of 2, 3, or 4 simultaneously active MUs was 10.7 +/- 2.5 Hz, 10.9 +/- 2.5 Hz and 10.6 +/- 2.4 Hz respectively. Hence at low innervation level there is no increase of firing rate with rising number of activated MUs. The upper normal limit of MU firing rate (3 sigma interval) is calculated as 17 Hz, irrespective whether 1, 2, 3 or 4 MUs are active within the recording area. Fifteen patients with partially denervated biceps muscles were investigated. Maximal firing rates were increased in 10 patients, all showing moderate or severe paresis (grade 1-3). In 10 patients suffering from myopathies firing rates always were normal. The presented data may serve as an additional criterion in evaluating MU firing rates during standard clinical EMG. PMID- 1313355 TI - Diagnostic value of computer analysis of multipeaked EMG spikes. AB - Computer analysis of absolute number of peaks per second and the number of peaks in the multipeaked spikes/sec was carried out in the EMG interference recordings of 5 healthy, 6 myopathic and 8 neuropathic subjects. The purpose of the study was to detect diagnostically different patterns. A spike was considered multipeaked if it had 6 or more peaks. The amplitude of elimination (baseline) was examined at 1: 5, 1: 10 and 1: 15 of the average amplitude per second. Both the number of peaks and the number of peaks in multipeaked spikes in the neuropathic and myopathic muscles showed statistically significant differences when compared to healthy muscles. This technique could give an indication for the differential diagnosis of myopathic, neuropathic or healthy state of the muscle. PMID- 1313356 TI - The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. AB - EGF-R positivity was shown to be present in 2500 (48%) of 5232 breast tumors in 40 different series of patients. The mean of the percentages of EGF-R positivity in the individual series reported by these 40 different groups of investigators is 45% (range 14-91%). Overall there are generally no clear differences between results obtained by radioligand binding assays, immunological methods, autoradiography, and measurement of EGF-R transcripts although the mean percentage of EGF-R-positive tumors determined by immunological methods tends to be somewhat lower. Nearly all studies indicate a negative relationship between EGF-R and steroid receptor status (28 of 31 studies for ER, 12/19 for PR) showing that EGF-R positivity is twice as high in ER or PR- negative tumors compared to ER or PR- positive tumors (approximately 50-60% vs. 30%). With regard to other prognostic factors the majority of investigators (10/18) also reported a significant (positive) correlation with tumor grade, but only a minority found a significant relationship between EGF-R status and patient age (2/9), menopausal status (1/7), histological type (3/7), tumor size (2/17), nodal status (5-9/20), ploidy (1/7), or proliferation indices (3/9). No relationship was observed with tumor insulin-like growth factor I receptor, PRL receptor (PRL-R), and LHRH receptor (LHRH-R) status, but an inverse relationship between EGF-R and somatostatin receptor may be present. However, it has to be stressed that the series in which the relationship between EGF-R status and other prognostic factors were investigated, contained relatively few patients (mostly less than 100). Therefore, when larger groups of patients are investigated, more significant relationships may be observed, especially with respect to nodal status, tumor ploidy, and proliferation indices. In fact, we calculated the presence of EGF-R positivity overall in 35% of 253 aneuploid tumors vs. in only 15% of 114 diploid tumors (P less than 0.0001). In addition most studies observed a trend, if no significant correlation, between higher EGF-R levels in tumors with the highest percentages of S-phase or Ki-67 expression. With regard to relapse-free and overall survival, five of nine different groups of investigators showed significant prognostic value of EGF-R after short-term (1- to 4-yr) follow up, indicating that patients with EGF-R-positive tumors have a poor prognosis. However, three of five groups with a maximal follow-up of at least 6 yr found only a tendency for any relationship between EGF-R status and long-term outcome. PMID- 1313357 TI - An immunoperoxidase method applied to the diagnosis of equine herpesvirus abortion, using conventional and rapid microwave techniques. AB - An indirect immunoperoxidase (IMP) technique was applied to cryostat and paraffin sections of liver from ten aborted equine foetuses. Equid herpesvirus type 1 (EHV 1) had been isolated from seven of them and EHV-4 from one: the remaining two were virologically negative and were not used as controls. In the eight virus infected cases the immunostaining revealed foci of cells exhibiting a distinct brown cytoplasmic and inclusion body pigmentation. No specific signal was present in the non-infected controls. The method also was adapted for incubation in a microwave oven, which allowed the total length of the procedure to be reduced to a minimum of 35 mins for cryostat sections, without significant loss of signal. PMID- 1313358 TI - Pathological findings in horses dying during an outbreak of the paralytic form of Equid herpesvirus type 1 (EHV-1) infection. AB - In 1988 an outbreak of the paralytic form of Equid herpesvirus type 1 (EHV-1) infection occurred on a stud farm and several animals died. This provided an opportunity to perform detailed pathological investigations to gain insights into the pathogenesis of this spontaneous disease. Two paretic mares, three foals, an aborted foetus and its non-paretic dam were examined. The endotheliotropism of the virus was clearly demonstrated by the use of an indirect immunoperoxidase (IP) stain. At autopsy, evidence of viral infection was widespread in the foetus and foals, but limited or absent in the mares, probably reflecting differences in their immune status. Vascular lesions were present in the central nervous system (CNS) of the foals as well as the adults; they resulted in minimal neural lesions in the foals. Severe changes in the upper and lower respiratory tracts were a particular feature in the foals, two of which exhibited extensive vasculitis and thrombosis in the lungs. The IP technique was of great value in locating antigen containing cells in the CNS of one mare when virus isolation was negative. It also revealed the presence of virus in less well documented sites such as the pancreas, gut, thyroid, uveal tract and the skin of the nares. PMID- 1313359 TI - Equine herpesviruses: are new techniques the solution to a practical problem? PMID- 1313360 TI - Diagnosis of equid herpesviruses -1 and -4 by polymerase chain reaction. AB - The polymerase chain reaction (PCR) is a sensitive technique used to detect DNA of viral pathogens. We have applied the technique to the detection of Equid herpesviruses-1 and -4 (EHV-1 and EHV-4) DNA within nasopharyngeal swab samples from horses. Ninety-eight samples from suspected field cases and in-contact horses were analysed. The assays were conducted blind and later decoded and compared with virus isolation data. Our results indicate that PCR is a sensitive and rapid technique for the diagnosis of EHV-1 and EHV-4 infection. PMID- 1313361 TI - Characterization of a recombinant chimeric plasminogen activator composed of a fibrin fragment-D-dimer-specific humanized monoclonal antibody and a truncated single-chain urokinase. AB - A recombinant chimeric plasminogen activator, MA-15C5Hu/scu-PA-32k, composed of a humanized fibrin fragment-D-dimer-specific monoclonal antibody (MA-15C5Hu) and a recombinant low-molecular-mass single-chain urokinase-type plasminogen activator, comprising amino acids Leu144-Leu411 (scu-PA-32k), was produced by cotransfecting Chinese hamster ovary (CHO) cells with the cDNA encoding the MA-15C5Hu light chain sequence and the cDNA encoding the MA-15C5Hu heavy-chain sequence fused with the cDNA encoding scu-PA-32k. Purified MA-15C5Hu/scu-PA-32k migrated as a 215-kDa band on non-reducing SDS/PAGE, which is consistent with a molecule composed of one antibody and two scu-PA-32k moieties. However, the chimera was obtained as a mixture of single-chain u-PA-32k (37%) and amidolytically inactive (50%) and active (13%) two-chain u-PA-32k, the latter of which was removed by immunoadsorption on a monoclonal antibody specific for two-chain urokinase. The fragment-D-dimer affinity and enzymatic properties of MA-15CHu/scu-PA-32k were similar to those of MA-15C5Hu or of scu-PA-32k. In an in vitro system composed of a 125I-fibrin-labeled human plasma clot submerged in citrated human plasma, MA 15C5Hu/scu-PA-32k had a 12-fold higher fibrinolytic potency than scu-PA-32k: 50% lysis in 2 h required 0.43 +/- 0.12 micrograms u-PA-32k equivalent of the chimera/ml versus 5.4 +/- 0.3 micrograms/ml of scu-PA-32k (mean +/- SEM, n = 4). Addition of purified fibrin fragment-D dimer reduced the fibrinolytic potency of MA-15C5Hu/scu-PA-32k in a concentration-dependent way, indicating that the increased potency is the result of antibody targeting. Thus, a recombinant humanized antifibrin antibody/u-PA chimera has been obtained in which only the variable domains of the antibody moiety are of non-human origin. The chimera has intact antigen-binding capacity, u-PA enzymatic activity and a significantly increased fibrinolytic potency in a plasma medium in vitro. PMID- 1313362 TI - Effect of benzyl alcohol on phospholipid transverse mobility in human erythrocyte membrane. AB - The effect of benzyl alcohol on the transverse mobility and repartition of phospholipids in the human erythrocyte membrane was investigated using electron spin resonance and morphological modification of red blood cells. Transmembrane internalization rates and equilibrium distribution in red blood cells of short chain spin-labeled phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine were strongly modified by treatment with 10-70 mM benzyl alcohol. A dual effect was observed: (a) at 4 degrees C and 37 degrees C there was an N-ethylmaleimide-sensitive, long lasting and fully reversible increase in the spin-labeled phosphatidylserine and phosphatidylethanolamine internalization rate; (b) at 37 degrees C, an enhancement of N-ethylmaleimide-insensitive fluxes of all the labeled phospholipids through the membrane occurred. Both effects were dose-dependent. Erythrocytes submitted to benzyl alcohol incubation also showed dose-dependent shape changes: an immediate one from discocytes to echinocytes, followed by a slower N-ethylmaleimide- and ATP-dependent change to stomatocytes. Moreover, benzyl alcohol treatment was shown to lead to enhanced hydrolysis of intracellular ATP. All the effects of benzyl alcohol can be described as an accumulation of labeled phosphatidylethanolamine (and labeled phosphatidylcholine at 37 degrees C) in the inner leaflet. This can be interpreted as a perturbation of the erythrocyte membrane, leading to an energy-consuming specific increase in aminophospholipid translocase activity, in addition to a slow and passive bidirectional flux of all phospholipids at 37 degrees C. PMID- 1313363 TI - Kinetic modeling of Sendai virus fusion with PC-12 cells. Effect of pH and temperature on fusion and viral inactivation. AB - We have studied the fusion activity of Sendai virus, a lipid-enveloped paramyxovirus, towards a line of adherent cells designated PC-12. Fusion was monitored by the dequenching of octadecyl-rhodamine, a fluorescent non exchangeable probe. The results were analysed with a mass action kinetic model which could explain and predict the kinetics of virus-cell fusion. When the temperature was lowered from 37 degrees C to 25 degrees C, a sharp inhibition of the fusion process was observed, probably reflecting a constraint in the movement of viral glycoproteins at low temperatures. The rate constants of adhesion and fusion were reduced 3.5-fold and 7-fold, respectively, as the temperature was lowered from 37 degrees C to 25 degrees C. The fusion process seemed essentially pH-independent, unlike the case of liposomes and erythrocyte ghosts. Preincubation of the virus in the absence of target cell membranes at neutral and alkaline pH (37 degrees C, 30 min) did not affect the fusion process. However, a similar preincubation of the virus at pH = 5.0 resulted in marked, though slow, inhibition in fusion with the fusion rate constant being reduced 8-fold. Viral preincubation for 5 min in the same acidic conditions yielded a mild inhibition of fusogenic activity, while preincubation in the cold (4 degrees C, 30 min) did not alter viral fusion activity. These acid-induced inhibitory effects could not be fully reversed by further viral preincubation at pH = 7.4 (37 degrees C, 30 min). Changes in internal pH as well as endocytic activity of PC-12 cells had small effect on the fusion process, thus indicating that Sendai virus fuses primarily with the plasma membranes. PMID- 1313364 TI - Specificity of the polycation-stimulated (type-2A) and ATP,Mg-dependent (type-1) protein phosphatases toward substrates phosphorylated by P34cdc2 kinase. AB - p34cdc2 kinase, a critical regulator of the cell cycle, has been shown to recognize the consensus sequence S/TP in proteins such as histone H1, the retinoblastoma gene product RB and the carboxyl-terminal domain of eukaryotic RNA polymerase II. Using phosphorylated synthetic peptides, representing the p34cdc2 phosphorylation sites in these proteins and histone H1 protein as substrates, we investigated the substrate specificity of the different oligomeric forms of the polycation-stimulated (PCS/type-2A) protein phosphatase and the active catalytic subunit of the ATP,Mg-dependent (AMDc/type 1) protein phosphatase. The results show that the oligomeric structure of the PCS phosphatases is an important determinant for efficient dephosphorylation. The trimeric PCSH1 and PCSM phosphatases are about 10-20-fold-better histone H1 phosphatases than the dimeric PCSH2 and PCSL phosphatases and about 100-fold better than the catalytic subunit (PCSC), suggesting a regulatory role for the 72-kDa, 65-kDa and 55-kDa subunits. The RB peptide = INGS(P)PRT(P)PRRGQNR, is preferred over phosphorylase a (8-fold) by the PCSH1 phosphatase and is about a 40-fold and 95-fold-better substrate for the PCSH1 phosphatase than for the PCSM and PCSL phosphatases, respectively. The primary structure surrounding the S/T(P)P motif, by itself a strong negative determinant for dephosphorylation, can harbour positive features which relieve the constraint imposed by the carboxyl-terminal proline. Thus, the RB peptide INGS(P)PRT(P)PRRGQNR, in which the T(P)P configuration is preferred over the S(P)P sequence, is an extremely good and specific substrate for the PCSH1 phosphatase (Km = 10 microM, Vmax = 3882 nmol.min-1.mg-1). The AMDC phosphatase is a poor phosphatase for all the phosphopeptides tested, unless Mn2+ is added. Its histone H1 phosphatase activity is much less sensitive than its phosphorylase a and phosphopeptide phosphatase activity to inhibition by the modulator or inhibitor-1. The results strongly suggest a role for the trimeric PCSH1 phosphatase in reversing the p34cdc2 phosphorylations. PMID- 1313365 TI - Characterization of the endogenous ADP-ribosylation of wild-type and mutant elongation factor 2 in eukaryotic cells. AB - Anti-[ADP-ribosylated elongation factor 2 (EF-2)] antiserum has been used to immunoprecipitate the modified form of EF-2 from polyoma-virus-transformed baby hamster kidney (pyBHK) cells [Fendrick, J. L. & Iglewski, W. J. (1989) Proc. Natl Acad. Sci. USA 86, 554-557]. This antiserum also immunoprecipitates a 32P labelled protein of similar size to EF-2 from a variety of primary and continuous cell lines derived from many species of animals. One of these cell lines, chinese hamster ovary CHO-K1 cells was further characterized. The time course of labelling of ADP-ribosylated EF-2 with [32P]orthophosphate was similar in pyBHK cells and in CHO-K1 cells. The kinetics of labelling were more rapid for cells cultured in 2% serum than 10% serum, with incorporation of 32P reaching a maximum at 6 h and 10 h, respectively. EF-2 mutants of pyBHK and CHO-K1 cells resistant to diphtheria-toxin-catalyzed ADP-ribosylation of EF-2 remain sensitive to cellular ADP-ribosylation of EF-2. The 32P-labelled moiety of ADP-ribosylated EF 2 was digested by snake venom phosphodiesterase and the product was identified as AMP. The same 32P-labelled tryptic peptide was modified by toxin in wild-type EF 2 and by the cellular transferase in mutant EF-2. When purified EF-2 from pyBHK cells was incubated with [carbonyl-14C]nicotinamide and diphtheria toxin fragment A, under conditions for reversal of the ADP-ribosylation reaction, [14C]NAD was generated. The results suggest that cellular ADP-ribosylated EF-2 exists in a variety of cell types, and the ribosylated product is identical to that produced by toxin ADP-ribosylation of EF-2, except in diphthamide mutant cells. Studies with the mutant cell lines indicate that the toxin and the cellular transferase, however, recognize different determinants at the ADP-ribose acceptor site in EF 2. The cellular transferase does not require the diphthamide modification of the histidine ring in the amino acid sequence of EF-2 for the transfer of ADP-ribose to the ring. Therefore, we would expect the cellular transferase active site to be similar to, but not identical to, the critical amino acids demonstrated in the active site of diphtheria toxin and Pseudomonas exotoxin A. PMID- 1313366 TI - Cloning and sequencing of arg3 and arg11 genes of Schizosaccharomyces pombe on a 10-kb DNA fragment. Heterologous expression and mitochondrial targeting of their translation products. AB - The Schizosaccharomyces pombe arginine anabolic genes encoding ornithine carbamoyltransferase (arg3) and acetylglutamate kinase/acetylglutamyl-phosphate reductase (arg11) were cloned by functional complementation of S. pombe arg3 and arg11 mutant strains from S. pombe DNA genomic libraries. Restriction analysis and sequencing of the two clones showed that both genes are located on a common DNA fragment. The arg3 gene encodes a 327-amino-acid polypeptide presenting a strong identity to Saccharomyces cerevisiae and human ornithine carbamoyltransferases. The arg11 gene encodes a 884-amino-acid polypeptide. The acetylglutamate kinase and acetylglutamate-phosphate reductase domains have been defined by their identity with the S. cerevisiae ARG5,6 protein. The cloned arg11 gene from S. pombe does not complement an arg5,6 mutation in S. cerevisiae, nor does the ARG5,6 gene complement the S. pombe arg11- mutation. In contrast, both ornithine-carbamoyltransferase-encoding genes function in S. pombe. However, the S. pombe arg3 gene complements only weakly an arg3 S. cerevisiae strain, which is in agreement with the low level of expression of the S. pombe gene in S. cerevisiae. The subcellular localization of both ornithine carbamoyltransferases in the two yeasts indicates that, in contrast to the S. pombe enzyme, more than 95% of the S. cerevisiae enzyme remains in the S. pombe cytoplasm. The low expression of S. pombe ornithine carbamoyltransferases in S. cerevisiae did not allow its localization. The promoters of S. pombe arg3 and arg11 genes do not present striking similarities among themselves nor with the promoters of the equivalent genes of S. cerevisiae. PMID- 1313367 TI - Microdiversity of human-plasma-membrane calcium-pump isoform 2 generated by alternative RNA splicing in the N-terminal coding region. AB - cDNA species covering the entire coding sequence of the human homologue of the rat plasma membrane Ca(2+)-ATPase (PMCA) isoform 2 have been isolated and characterized. The deduced amino acid sequence shows 99% identity with that of the rat protein and can be aligned with the latter without gaps except for one 14 amino-acid-residue insert in the region immediately preceding the putative phospholipid-sensitive domain in the human pump. cDNA clones isolated by anchored polymerase-chain reaction revealed additional microheterogeneity in the same N terminal PMCA2-coding region. Alternative RNA splicing involving a region of 135 nucleotides generates three types of cDNA. One does not contain any of the 135 bp, and the other two contain 42 bp or the entire 135 bp of the optional sequence. Analysis of genomic DNA indicates that this sequence is encoded by three separate exons of 33, 60 and 42 bp. Although each of these exons could be inserted into the mRNA without changing the reading frame, polymerase-chain amplifications using cDNA libraries from several human tissues show that the 33 bp and the 60-bp exons are never independently used during splicing. The unequal distribution of the splice variants suggests tissue-specific regulation of the alternative-splicing pathways and indicates a functional specialization of the encoded isoform subtypes. PMID- 1313368 TI - Plant mitochondrial F0F1 ATP synthase. Identification of the individual subunits and properties of the purified spinach leaf mitochondrial ATP synthase. AB - Spinach leaf mitochondrial F0F1 ATPase has been purified and is shown to consist of twelve polypeptides. Five of the polypeptides constitute the F1 part of the enzyme. The remaining polypeptides, with molecular masses of 28 kDa, 23 kDa, 18.5 kDa, 15 kDa, 10.5 kDa, 9.5 kDa and 8.5 kDa, belong to the F0 part of the enzyme. This is the first report concerning identification of the subunits of the plant mitochondrial F0. The identification of the components is achieved on the basis of the N-terminal amino acid sequence analysis and Western blot technique using monospecific antibodies against proteins characterized in other sources. The 28 kDa protein crossreacts with antibodies against the subunit of bovine heart ATPase with N-terminal Pro-Val-Pro- which corresponds to subunit F0b of Escherichia coli F0F1. Sequence analysis of the N-terminal 32 amino acids of the 23-kDa protein reveals that this protein is similar to mammalian oligomycin sensitivity-conferring protein and corresponds to the F1 delta subunit of the chloroplast and E. coli ATPases. The 18.5-kDa protein crossreacts with antibodies against subunit 6 of the beef heart F0 and its N-terminal sequence of 14 amino acids shows a high degree of sequence similarity to the conserved regions at N terminus of the ATPase subunits 6 from different sources. ATPase subunit 6 corresponds to subunit F0a of the E. coli enzyme. The 15-kDa protein and the 10.5 kDa protein crossreact with antibodies against F6 and the endogenous ATPase inhibitor protein of beef heart F0F1-ATPase, respectively. The 9.5-kDa protein is an N,N'-dicyclohexylcarbodiimide-binding protein corresponding to subunit F0c of the E. coli enzyme. The 8.5-kDa protein is of unknown identity. The isolated spinach mitochondrial F0F1 ATPase catalyzes oligomycin-sensitive ATPase activity of 3.5 mumol.mg-1.min-1. The enzyme catalyzes also hydrolysis of GTP (7.5 mumol.mg-1.min-1) and ITP (4.4 mumol.mg-1.min-1). Hydrolysis of ATP was stimulated fivefold in the presence of amphiphilic detergents, however the hydrolysis of other nucleotides could not be stimulated by these agents. These results show that the plant mitochondrial F0F1 ATPase complex differs in composition from the other mitochondrial, chloroplast and bacterial ATPases. The enzyme is, however, more closely related to the yeast mitochondrial ATPase and to the animal mitochondrial ATPase than to the chloroplast enzyme. The plant mitochondrial enzyme, however, exhibits catalytic properties which are characteristic for the chloroplast enzyme. PMID- 1313369 TI - Haematological prognostic indices after myocardial infarction: evidence from the diet and reinfarction trial (DART). AB - Data from the Diet and Reinfarction Trial were examined to check the prognostic effects of plasma fibrinogen, plasma viscosity, white blood cell count, haemoglobin and mean platelet volume in 92 deaths among 1755 men who had recently recovered from acute myocardial infarction. All these variables were significantly associated with all-cause mortality over the following 18 months (haemoglobin negatively, the others positively). Those who gave up smoking following their infarct had a lower mortality than those who continued to smoke (4.1% and 7.9% respectively), and this effect appeared to be mediated by fibrinogen levels. Smoking habit accounted for only part of the prognostic effect of fibrinogen and white blood cell count. Haematological variables have an important prognostic significance after myocardial infarction. Cessation of smoking after myocardial infarction is worthwhile and has a favourable effect on plasma fibrinogen. PMID- 1313370 TI - Effect of diethyldithiocarbamate on the activity of nitric oxide-releasing vasodilators. AB - The effect of diethyldithiocarbamate (DETC, 10(-3) M) on the vasorelaxant activity of acetylcholine, nitric oxide (NO), nitrite, glyceryl trinitrate or dinitrosyl iron cysteine complexes was studied in isolated rat aortic rings contracted with norepinephrine. Pretreatment of these segments with DETC attenuated the vasorelaxation induced by vasodilators and prevented the subsequent restoration of vessel tone, whereas DETC added after the vasodilators induced a rapid restoration of tone. The inhibitory effect of DETC was due to the trapping of NO by a complex of DETC with Fe2+ formed in the tissue. PMID- 1313371 TI - Antinociceptive actions of different classes of excitatory amino acid receptor antagonists in mice. AB - Intrathecal (i.t.) injection of the competitive and selective N-methyl-D aspartate (NMDA) receptor antagonists DL-2-amino-5-phosphonopentanoic acid (AP5), D-2-amino-7-phosphonoheptanoic acid (AP7), beta-D-aspartylaminomethyl phosphonic acid (Asp-AMP), 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and gamma-D-glutamylaminomethyl phosphonic acid (Glu-AMP) produced dose-dependent and reversible analgesic effects in the mouse hot-plate and formalin tests of nociception. They were slightly more potent in the formalin test but had no or negligible effects in the tail-flick test. The non-selective or non-NMDA receptor antagonists 6-cyano-7-nitro-quinoxalinedione (CNQX), 6,7-dinitro-quinoxalinedione (DNQX), gamma-D-glutamylglycine (gamma DGG), gamma-glutamylaminomethyl sulphonic acid (GAMS), kynurenic acid, cis-2,3-piperidine dicarboxylic acid (cis-PDA; partial agonist) and p-bromobenzoyl piperazine dicarboxylic acid (pBB-PzDA) had the same efficacy in the mouse hot-plate, tail-flick and formalin tests (gamma DGG and pBB-PzDA were not tested in the formalin test). This heterogeneous group of antagonists was somewhat more potent in the tail-flick test and slightly less potent in the formalin test than in the hot-plate test. Of the two glycine site antagonists tested, 7-chlorokynurenic acid (7-Cl-Kyn) and (+/-)-3-amino-1-hydroxy 2-pyrrolidone (HA-966), the effect of the latter was compatible with selective action at the NMDA receptor complex while the action of the former was comparable to those of non-selective excitatory amino acid (EAA) receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313372 TI - Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats. AB - The mechanism of the inhibitory action of rebamipide, a new mucosal protective drug, was studied using rats with diethyldithiocarbamate-induced gastric antral ulcers. Rebamipide reduced ulcer formation and inhibited the elevation in lipid peroxide concentration in the gastric mucosa. Rebamipide inhibited both luminol- and lucigenin-dependent chemiluminescence of neutrophils activated by formyl methionyl-leucyl-phenylalanine. Rebamipide did not alter the reduction of cytochrome c induced by the xanthine-xanthine oxidase system or the NADPH dependent microsomal lipid peroxidation in the liver. These findings suggest that rebamipide prevents diethyldithiocarbamate-induced gastric ulcer formation by inhibiting neutrophil activation. PMID- 1313373 TI - Effect of endotoxin on circulating cyclic GMP in the rat. AB - The aim of this study was to investigate the possible use of plasmatic cyclic GMP as an index of L-arginine/nitric oxide (L-Arg/NO) pathway activation by E. coli endotoxin in vivo. Endotoxin (20 mg kg-1 i.p.) caused a time-dependent increase in plasmatic cyclic GMP in anaesthetised rats which corresponded with the time course of L-Arg/NO pathway activation in aortas from the same rats, but was not prevented by a specific inhibitor of this pathway, NG-nitro-L-arginine methyl ester (1 mg kg-1 or 20 mg kg-1 h-1 i.v.). Elevated plasmatic cyclic GMP was however also associated with an increased plasma concentration of atrial natriuretic peptide (ANP) in endotoxin-treated rats. We conclude that plasma cyclic GMP cannot be used as a direct marker of L-Arg/NO pathway activation by endotoxin but may instead be a reflection of an endotoxin-induced increase in plasma ANP activity. PMID- 1313374 TI - Solubilization of active GLP-1 (7-36)amide receptors from RINm5F plasma membranes. AB - Glucagon-like peptide-1 (7-36)amide (GLP-1 (7-36)amide) represents a physiologically important incretin in mammals including man. Receptors for GLP-1 (7-36)amide have been described in RINm5F cells. We have solubilized active GLP 1(7-36)amide receptors from RINm5F cell membranes utilizing the detergents octyl beta-glucoside and CHAPS; Triton X-100 and Lubrol PX were ineffective. Binding of radiolabeled GLP-1(7-36)amide to the solubilized receptor was inhibited concentration-dependently by addition of unlabeled peptide. Scatchard analysis of binding data revealed a single class of binding sites with Kd = 0.26 +/- 0.03 nM and Bmax = 65.4 +/- 21.24 fmol/mg of protein for the membrane-bound receptor and Kd = 22.54 +/- 4.42 microM and Bmax = 3.9 +/- 0.79 pmol/mg of protein for the solubilized receptor. The binding of the radiolabel to the solubilized receptor was dependent both on the concentrations of mono- and divalent cations and the protein/detergent ratio in the incubation buffer. The membrane bound receptor is sensitive to guanine-nucleotides, however neither GTP-gamma-S nor GDP-beta-S affected binding of labeled peptide to solubilized receptor. These data indicate that the solubilized receptor may have lost association with its G-protein. In conclusion, the here presented protocol allows solubilization of the GLP-1(7 36)amide receptor in a functional state, and opens up the possibility for further molecular characterization of the receptor protein. PMID- 1313375 TI - A large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor. AB - A new family of mosaic proteins is defined by sequence analysis. The family is characterized by a 260 residue domain common to proteins of apparently diverse function and tissue specificity: sperm receptors Zp2 and Zp3, betaglycan (also called TGF-beta type III receptor), uromodulin, as well as the major zymogen granule membrane protein (GP-2). The location of the common domain is similar with respect to putative transmembrane regions. The results lead to the hypothesis that this type of domain has a common tertiary structure and that there is a functional similarity in the recognition mechanism of the sperm receptor system and the TGF-beta receptor complex. PMID- 1313376 TI - The non-equivalence of binding sites of coenzyme quinone and rotenone in mitochondrial NADH-CoQ reductase. AB - The fluorescent probe erythrosine 5'-iodoacetamide (ER) binds to mitochondrial NADH-CoQ reductase (Complex-I) accompanied by an enhancement of the fluorescence intensity. The binding of the CoQ analogue, 2,3-dimethoxy-5-methyl-6-decyl-1,4 benzoquinone (DB), decreased the fluorescence intensity of the ER:Complex-I system. The 'site 1' inhibitor rotenone did not decrease the fluorescence intensity showing the non-identical nature of the binding sites of DB and rotenone. Also, the reduced form of DB did not decrease the fluorescence intensity. The decrease of the fluorescence intensity by DB was shown to be due to the removal of bound ER by DB. The rapid kinetics of ER binding was studied by temperature-jump relaxation. While DB caused complete elimination of the relaxation process in the ER:Complex-I system, rotenone caused only a decrease in the relaxation rate, suggesting conformational change. The relaxation rate showed a pH dependence with a maximum around pH 7.5. PMID- 1313377 TI - Preparation of oligozoospermic and/or asthenozoospermic semen for intrauterine insemination using the SpermPrep semen filtration column. AB - OBJECTIVE: To improve the quality of oligozoospermic and/or asthenozoospermic semen by the SpermPrep (Fertility Technologies Inc., Natick, MA) semen filtration column. DESIGN: The SpermPrep column was applied for semen manipulation in oligozoospermia and/or asthenozoospermia (sperm count less than 20 x 10(6)/mL, sperm motility less than 40%). After concentration of motile sperm using a 40% Percoll density gradient centrifugation, the sperm suspension was filtered through the SpermPrep column. The percentage yield of motile sperm by the SpermPrep method was compared with those by a two-layer Percoll density gradient (Pharmacia, Uppsala, Sweden) centrifugation and a swim-up method. Infertile couples with poor quality semen were treated with intrauterine insemination (IUI) with motile sperm by the three preparations through three cycles. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital. PATIENTS: Twenty-one couples with long-standing infertility because of poor quality semen. MAIN OUTCOME MEASURE: Recovery of motile sperm, sperm motility, and outcome of IUI were evaluated among three semen preparations. RESULTS: Motility was improved by the SpermPrep method in 32 of 33 cases of oligozoospermia and/or asthenozoospermia. Percentage yield of motile sperm by the SpermPrep method was significantly greater than those by the two-layer Percoll density gradient and swim-up methods (42.7 +/- 4.6 versus 22.1 +/- 3.1 and 13.8 +/- 3.5), but there is no significant difference in the sperm motility among three semen preparations. After one treatment cycle for each preparation, 2 of 21 women conceived after IUI with motile sperm separated in the SpermPrep method. CONCLUSIONS: The SpermPrep method is an improved semen manipulation method for oligozoospermia and/or asthenozoospermia. PMID- 1313378 TI - [The cyclic nucleotide content of the blood plasma in rabbits administered izadrin]. AB - The influence of cyclic nucleotides system on the rabbit resistance to injection of exogenic sympathomimetic was studied in this experiment. Absolute concentration value and ratio of cAMP to cGMP in animals with different resistance were determined. PMID- 1313379 TI - [New approaches to the system regulating the aggregate state of the blood]. AB - It is shown that in the organism there is an adrenoreactive system of the aggregate blood state regulation (ABSR) including alpha- and beta-adrenoreactive structures of hypothalamus, amygdalar complex and peripheral vessels. The ABSR system consists of two subsystems, each possessing specific action. Both subsystems interact in the reciprocal manner by the mechanism of feedbacks and can exert a modulating effect on each other. PMID- 1313380 TI - [The effect of regulatory peptides on water absorption in the large intestine of the frog]. AB - Preparation of isolated large intestine of the frog was filled with Ringer's solution diluted with distilled water (1:5) and was placed into the glass with normal Ringer's solution. The preparation was weighed within every 30 min and the osmotic permeability was determined for water of the mucous and serous layers of the intestine. Then one of the peptides was added to Ringer's solution and the experiment continued. It is stated that bombesin, neurotensin, encephalins, substance P, somatostatin, pituitrin are able to change liquid absorption from the large intestine cavity when the concentration of Ringer's solution in the cavity and from its serous surface is the same. Bombesin and neurotensin inhibited while encephalins stimulated liquid absorption and these effects depended on the transport of ions. Liquid absorption by the osmotic gradient decreased using bombesin, substance P and increased using somatostatin. More complex peptide-peptide relations are observed if using pituitrin and other peptides. cAMP is shown to participate in bombesin effects. PMID- 1313381 TI - [The characteristics of the alpha-adrenergic regulation of the cardiovascular system in middle-aged and elderly subjects]. AB - 97 practically healthy young adult, elderly and old people were examined to study the age-associated changes in alpha-adrenergic regulation of the cardiovascular system. The values of central and renal hemodynamics, systolic and diastolic cardiac functions, skin and bulbar microcirculation and arterial blood pressure were determined in dynamics after injection of the alpha-stimulator phenylephrine (0.15 mg/kg of body mass intramuscularly) or alpha-blocker prazosin (0.015 mg/kg of body mass orally). In old age alpha-adrenergic effects on the heart were found to decrease. In elderly and old people the changes of peripheric blood circulation prevail in the structure of hemodynamic shifts arising in stimulation and alpha-adrenergic receptors blockage. PMID- 1313382 TI - Hepatitis C: basic and clinical studies. AB - The HCV, a single stranded RNA virus belonging to the family of flavivirus, has been identified as the probable cause of the majority of cases of transfusion associated NANB hepatitis and community-acquired NANB hepatitis in Japan. The hepatitis virus is present in a least 2% of the blood donor population and is extremely common in high risk groups, such as hemophiliacs and hemodialysis patients. The contribution of HCV infection to sporadic, acute and chronic hepatitis, liver cirrhosis and primary liver cancer has been established. Furthermore anti-HCV in 20% of alcoholic patients with liver injury suggest that HCV may be etiologically associated with liver disease previously attributed to other causes. Therapy of acute and chronic liver disease associated with HCV infection is likely to be undertaken with recombinant IFN alpha in the future to prevent the progression of the disease from acute hepatitis to chronic hepatitis, and from chronic hepatitis to liver cirrhosis or primary liver cancer. However the prevention of HCV infection will be the goal, in addition to screening of donor blood and exclusion to a large degree of positive units likely to decrease the incidence of post-transfusion hepatitis. PMID- 1313384 TI - Clinical evaluation of tissue plasminogen activator (t-PA) levels in patients with liver diseases. AB - Tissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n = 30); fulminant hepatitis (FH, n = 36); chronic inactive hepatitis (CIH, n = 57); chronic active hepatitis (CAH, n = 39); compensated liver cirrhosis (cLC, n = 78); decompensated liver cirrhosis (dLC, n = 84); hepatocellular carcinoma (HCC, n = 64); advanced hepatocellular carcinoma (aHCC, n = 28); and compared with that of a control group (n = 106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin alpha 1-plasmin inhibitor complex (PIC), plasminogen (Plg), FDP, AT III and alpha 2-plasmin inhibitor (alpha 2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313383 TI - Changes in the markers related to collagen synthesis in the liver of chronically alcohol treated rats. AB - In order to clarify the roles of Ito cells in the development of alcoholic fibrosis, markers related to collagen synthesis in the liver were analyzed in chronically alcohol treated rats. The livers were obtained from rats fed a diet containing alcohol (alcohol group) and those fed a control diet (control group) for 4 weeks. Prolyl hydroxylase (PH) activity in the whole liver tissue did not differ in the alcohol and control groups. However, the activity in the isolated Ito cells was significantly higher in the alcohol group than in the control group. Immunoreactive PH beta-subunit contents in the liver and serum were significantly higher in the alcohol group than in the control group. Hydroxyproline contents in the liver did not differ in either groups. Immunohistochemically, type IV collagen and laminin were clearly stained along with the sinusoid in the livers of the alcohol group. However, the staining reactions were very weak in the control group. Staining reactions to types I and III collagen were very weak or almost absent in the livers of both groups. Desmin positive cells, along with the sinusoid, increased significantly in the alcohol group, especially at the centrilobular area, suggesting that the number of Ito cell increase in the centrilobular areas of the alcohol treated rats. These results suggest that type IV collagen and laminin synthesis increase in the Ito cells of chronically alcohol treated rats, although clear evidence of hepatic fibrosis was not obtained. This increase may be related to capillarization of the sinusoids and finally to the development of perisinusoidal fibrosis in alcoholics. PMID- 1313385 TI - Ultrasound study in the diagnosis of primary Budd-Chiari syndrome (obstruction of the inferior vena cava). AB - Primary Budd-Chiari syndrome, obstruction of the hepatic portion of the inferior vena cava (IVC), is a rare disorder, but relatively prevalent in the Far East, northern India and Africa. Ultrasound examination was carried out on 9 patients with primary Budd-Chiari syndrome. There were 5 men and 4 women aged 27-60 years. In all the 9 cases, the diagnosis was confirmed by cavography and liver histology. Moreover, 7 of the 9 subsequently underwent radical operation using a patch graft. Ultrasonic study showed several characteristic findings suggestive of the syndrome, and frequencies of the main findings were as follows: 1) an echogenic obstructing membrane; 22.2%, 2) segmental obstruction of the IVC; 77.8%, 3) occlusion of the major hepatic veins at the juxtacaval portion; 100%, 4) enlarged inferior right hepatic veins; 55.6%, 5) abnormal intrahepatic venous structures and collaterals; 88.9%. Of these findings, 5) was the most prominent and most characteristic in the diagnosis of the syndrome. It is necessary for early detection of this entity to evaluate carefully intrahepatic venous abnormalities and patency of either the IVC or major hepatic veins on ultrasonic examination. The careful examination for Budd-Chiari syndrome should be done in cases with cryptogenic liver cirrhosis, particularly in countries where the prevalence of the syndrome is high. PMID- 1313386 TI - The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase. AB - We describe the cloning of a multifunctional folic acid synthesis (fas) gene from Pneumocystis carinii. The nucleotide sequence contains an open reading frame interrupted by three introns, that encodes a protein of 740 amino acids with an Mr of 97,278. The predicted Fas protein has homology to two enzyme domains, dihydropteroate synthase and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, both of which are involved in folate synthesis, and at least one other region of unknown function. PMID- 1313387 TI - Measurement of hygromycin B phosphotransferase activity in crude mammalian cell extracts by a simple dot-blot assay. AB - Hygromycin B (Hy) resistance, encoded by the prokaryotic gene hph, is commonly used as a dominant selectable marker for gene transfer experiments in mammalian cells. We describe a simple, quantitative dot-blot assay for measuring the activity in crude mammalian cell extracts of Hy phosphotransferase, the product of the hph gene. The assay shows no cross interference with substrates for neomycin phosphotransferase II, the product of the commonly used marker gene neo; hph and neo may thus be useful as a set of two non-interfering selectable marker and reporter genes for gene transfer experiments in mammalian cells. PMID- 1313388 TI - A day hospital program for dual diagnosis patients in a VA Medical Center. AB - A day hospital program for patients with mental illness and substance abuse problems at a Veterans Affairs medical center uses nonconfrontational group therapy as the primary treatment modality. The goals of the six-to-eight-week program are to reduce substance abuse, improve medication compliance, and reduce the number of hospitalizations. Aftercare is available for patients who complete the program. The authors suggest that patients' ability to relate well to others in group therapy is the primary factor influencing successful outcome. During a 30-month period, 66 percent of the patients admitted to the day hospital program completed it. Three cases illustrating the variable outcomes of patients treated in the program are presented. PMID- 1313389 TI - A profile of problem drinkers in public mental health services. AB - Psychiatric patients with alcohol problems are generally considered more challenging to treat and more demanding of public psychiatric services than other patients. This study of new admissions to a county mental health system in California examined differences between problem drinkers and nonproblem drinkers in clinical and demographic characteristics and in the demands they placed on services. Problem drinkers experienced more severe emotional distress at intake; were more likely to have financial, legal, and employment problems; and were more likely to be involved with illicit drugs. They made greater demands on clinical resources and also required more social services, such as income supports, case management, and vocational services. The study indicates that to meet the varied needs of psychiatric patients with drinking problems, public mental health services should develop stronger ties not only with substance abuse services but also with social service and criminal justice agencies. PMID- 1313390 TI - Neuroendocrine differentiation in human prostatic carcinoma. AB - Endocrine-paracrine (APUD, neuroendocrine) cells are located in the prostatic ductal and acinar epithelium. These cells are of the open and closed type and have dendritic processes. There is a wide range of secretory granule morphology presumably indicating a variety of different cell "types." Secretory immunoreactive peptides include serotonin, calcitonin (and related peptides), somatostatin, bombesin-like, thyroid-stimulating hormone-like (beta chain), and alpha-glycoprotein chain-like. These cells may function by endocrine, paracrine, neurocrine, and lumencrine mechanisms and play an important regulatory role both during growth and differentiation of the prostate as well as in the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma is a frequent occurrence and manifests itself in several forms, including (1) small cell carcinoma, (2) carcinoid and carcinoid-like tumors, and (3) conventional adenocarcinoma with focal neuroendocrine differentiation. This latter pattern is the most common, and there is evidence that all or nearly all prostatic adenocarcinomas show at least some focal neuroendocrine differentiation. A review of the world's literature on this topic is included. Neuroendocrine differentiation generally portends a poorer prognosis but may also correlate directly with the grade. There is some evidence to suggest that neoplastic cells with neuroendocrine differentiation are resistant to hormonal therapy. Eutopic and ectopic hormone production may allow screening for prostatic carcinoma and/or monitoring for recurrence of prostatic carcinomas. Finally, the more basic implications of endocrine-paracrine cells and neuroendocrine differentiation are speculated on in reference to prostatic carcinogenesis and autocrine/paracrine tumor growth factor activity. PMID- 1313391 TI - Immunohistochemical demonstration of chromogranins A and B in neuroendocrine tumors of the lung. AB - Fifty neuroendocrine tumors of the lung (16 carcinoids, two atypical carcinoids/well-differentiated neuroendocrine carcinomas [WDNCs], 13 neuroendocrine carcinomas of intermediate cell type [SCNCs], and 19 neuroendocrine carcinomas of small cell type [SCNs]) were immunohistochemically investigated with antibodies against chromogranins A and B. All carcinoids and WDNCs were positive for both chromogranins A and B, whereas in cases of ICNC and SCNC both markers were only expressed in six and five cases, respectively. One ICNC was only positive for chromogranin A. In cases of SCNC five tumors were exclusively positive for chromogranin A and six were positive only for chromogranin B. Chromogranins are therefore excellent markers for the immunohistochemical demonstration of carcinoids and WDNCs. It may be speculated that expression of chromogranins in cases of ICNC and SCNC represents a higher degree of differentiation in these tumors. PMID- 1313392 TI - Na(+)-Ca2+ exchange, myoplasmic Ca2+ concentration, and contraction of arterial smooth muscle. AB - Na(+)-Ca2+ exchange is proposed to be an important regulator of myoplasmic intracellular Ca2+ concentration ([Ca2+]i) and contraction in vascular smooth muscle. We investigated the role of Na(+)-Ca2+ exchange in regulating [Ca2+]i in swine carotid arterial tissues that were loaded with aequorin to allow simultaneous measurement of [Ca2+]i and force. Reversal of Na(+)-Ca2+ exchange, by reduction of extracellular Na+ concentration ([Na+]o) to 1.2 mM, induced a large increase in aequorin-estimated [Ca2+]i and a low [Ca2+]i sensitivity. The contraction induced by 1.2 mM [Na+]o was partially caused by depolarization and opening of L-type Ca2+ channels because 10 microM diltiazem partially attenuated the 1.2 mM [Na+]o-induced increases in [Ca2+]i. High dose ouabain (10 microM), a putative endogenous Na+,K(+)-ATPase inhibitor, increased both [Ca2+]i and force. However, the increases in [Ca2+]i and force were mostly blocked by 10 microM phentolamine, suggesting the predominant effect of ouabain was to increase norepinephrine release from nerve terminals. In the presence of 10 microM phentolamine, 10 microM ouabain slightly accentuated 1 microM histamine-induced increases in [Ca2+]i and force. The ouabain dose necessary to induce contraction in the absence of phentolamine was significantly less than the ouabain dose necessary to accentuate histamine-induced contractions in the presence of phentolamine. These results suggest that Na(+)-Ca2+ exchange exists in swine arterial smooth muscle. These data also suggest that ouabain (which should increase [Na+]i and inhibit Na(+)-Ca2+ exchange) primarily enhances contractile function in the swine carotid artery by releasing catecholamines from nerve terminals; direct action of Na+,K(+)-ATPase inhibitors on smooth muscle appears to occur only with very high doses. PMID- 1313393 TI - C-type natriuretic peptide inhibits thrombin- and angiotensin II-stimulated endothelin release via cyclic guanosine 3',5'-monophosphate. AB - We examined the inhibitory effect of porcine C-type natriuretic peptide (CNP) on endothelin-1 secretion stimulated by thrombin and angiotensin II (Ang II) in cultured porcine endothelial cells. The results were compared with the effects of atrial (ANP) and brain (BNP) natriuretic peptides. Thrombin and Ang II produced a concentration-dependent stimulation of immunoreactive endothelin-1 secretion, and porcine CNP-22 potently inhibited this stimulated secretion in a concentration dependent manner. CNP-22 had a stronger inhibitory effect than either porcine ANP(1-28) or porcine BNP-26. In addition, CNP potently increased the cellular level of cyclic guanosine 3',5'-monophosphate (GMP), with the inhibition of immunoreactive endothelin-1 secretion in response to thrombin and Ang II being paralleled by the increase in the cyclic GMP level. The increase of cyclic GMP produced by CNP was also greater than that due to porcine ANP(1-28) or porcine BNP-26. The immunoreactive endothelin-1 in the culture medium had two components on high-performance liquid chromatography; the major one corresponded to endothelin-1 (1-21) and the minor one to big endothelin-1 (porcine 1-39). Treatment with CNP did not affect this profile. Our results suggest that CNP probably inhibits the endothelin-1 secretion stimulated by thrombin and Ang II through a cyclic GMP-dependent process. The increase of cyclic GMP levels and the inhibition of immunoreactive endothelin-1 secretion produced by CNP appear to be greater than those produced by ANP or BNP. PMID- 1313394 TI - Pressure natriuresis in rats during blockade of the L-arginine/nitric oxide pathway. AB - The natriuretic response was studied in anesthetized rats during the intravenous infusion of L-arginine analogues to inhibit the production of endothelium-derived nitric oxide. In an initial experimental series, rats were administered saline vehicle or vehicle containing 300 mumol/kg body wt N omega-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester, N omega-monomethyl-D-arginine, or L arginine. Infusion of the competitive inhibitors N omega-monomethyl-L-arginine and N omega-nitro-L-arginine methyl ester significantly increased mean arterial pressure to 155 +/- 3 and 145 +/- 5 mm Hg, respectively, compared with a mean arterial pressure of 118 +/- 3 mm Hg determined in the vehicle control group. Sodium excretion averaged 3.27 +/- 1.08 and 2.52 +/- 0.78 mu eq/min in the N omega-monomethyl-L-arginine- and N omega-nitro-L-arginine methyl ester-treated rats, respectively, and each was significantly higher than the basal sodium excretion of 0.20 +/- 0.05 mu eq/min in the vehicle-treated control animals. Plasma renin activity was significantly lower in the N omega-monomethyl-L arginine- and N omega-nitro-L-arginine methyl ester-treated groups than in the vehicle-treated group. Neither L-arginine nor N omega-monomethyl-D-arginine administration significantly altered any of the measured variables compared with vehicle alone. In a second experimental series, an adjustable snare was placed around the suprarenal aorta for the purpose of controlling renal perfusion pressure independently of increases in the systemic mean arterial pressure initiated by infusion of N omega-nitro-L-arginine methyl ester (75 mumol/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313395 TI - On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats. AB - We tested the hypothesis that a genetically determined increase in renal alpha adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor density with systolic blood pressure in 45 rats of an F2 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids but were unable to detect significant cosegregation between either receptor density or blood pressure. In a second study, we determined renal alpha 1- and alpha 2-adrenergic receptor density in Wistar-Kyoto and spontaneously hypertensive rat kidneys that were transplanted into an F1 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids. Although Wistar-Kyoto kidneys lowered blood pressure in these animals and spontaneously hypertensive rat kidneys increased blood pressure, renal alpha adrenergic receptor densities were similar in membranes from both types of kidneys. Since rat kidney coexpresses alpha 1A- and alpha 1B-adrenergic receptors, we also investigated whether differential regulation of these two subtypes might conceal ongoing alterations. The alpha 1A/alpha 1B-adrenergic receptor ratio, however, was similar in Wistar-Kyoto rats, spontaneously hypertensive rats, and F1 rats transplanted with a kidney from either strain. Taken together these data do not support the hypothesis that genetically determined alterations of renal alpha-adrenergic receptor numbers play an important role in the development of elevated blood pressure in the spontaneously hypertensive rat. PMID- 1313396 TI - Leukotriene release from neutrophils of patients on hemodialysis with cellulose membranes. AB - The role of cytokines in patients with chronic renal failure is currently under investigation. We therefore studied the release of leukotriene B4 (LTB4) from polymorphonuclear leukocytes (PMN) in stable dialysis patients treated with two different cellulose membranes, Cuprophan and Hemophan, a modified cellulose with less complement activation. Six patients were treated for four weeks with Cuprophan then switched to Hemophan for another four weeks. Before and after the last treatment of each period, PMN were separated from 20 ml heparinized blood by FICOLL density gradient centrifugation. Portions of 5 x 10(6) PMN were resuspended in Hanks' buffer and stimulated for 5 minutes with calcium ionophore A23187 (5 micrograms/ml). LTB4 in cell supernatants was determined by specific radioimmunoassay. PMN from dialysis patients before HD released significantly (p less than 0.01) more LTB4 than healthy donors. No significant difference between pre- and post-dialysis values was observed with Cuprophan or Hemophan dialyzers. Our data suggest that the acute effects of blood membrane interaction with either complement activating or non-activating dialyzers do not lead to changes in post dialysis leukotriene metabolism, but leukotriene production is enhanced chronically in dialysis patients. PMID- 1313397 TI - Cellular heterogeneity of DNA/total-protein content in human lung tumors, as determined by flow cytometry. AB - With the aim of distinguishing neoplastic cell sub-populations of different prognostic and diagnostic significance, dual-parameter measurements (DNA/protein) have been simultaneously determined in a (256, 256) channel matrix in lung samples derived from 110 patients affected by neoplastic and non-neoplastic lung diseases. Biparametric analysis demonstrated that cells with abnormally high red fluorescence (i.e., protein content), which is indicative of unbalanced growth, were often observed in malignant tumors as compared with normal lung samples. Furthermore, the dual-parameter analysis allowed recognition of additional aneuploid tumor-cell lines, indicating that the frequency of cytometrically determined diploid tumor is lower than that previously described by DNA monoparametric analysis. The recognition of aneuploid subpopulations by dual parameter analysis in clinically and histologically negative one-parameter flow cytometric "diploid" samples assumes important diagnostic value. The results have also shown the presence of multiple protein sub-populations in clones with the same ploidy value, indicating a higher level of cellular heterogeneity than demonstrated by DNA monoparametric measurements. PMID- 1313398 TI - Serum oncoproteins and growth factors in asbestosis and silicosis patients. AB - Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3 26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses. PMID- 1313399 TI - Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate). AB - Pathological effects of asbestos are probably dependent on the size and surface properties of the fibers. Surface-modified chrysotile fibers were injected into the pleural cavity of rats to investigate the potency of the fiber to induce mesothelioma. Chrysotile fibers were modified by a phosphorylation process, resulting in the presence of phosphorus at the fiber surface. Phosphorylated samples were characterized by enhanced durability and reduced affinity for biological macromolecules. Five samples were tested: 1 untreated and 4 phosphorylated. ChrP1, ChrP2 and ChrP3 corresponded to phosphorylated samples obtained by first, second and third passages through an Alpine classifier; Pm was defibrillated ChrP1. The number of fibers per microgram and the size distribution were determined by transmission electron microscopy and classified in 4 size groups. Groups of 35 rats were inoculated with 20 mg of fibers suspended in 0.9% NaCl solution. No mesothelioma was found in the saline controls. All fiber samples were proficient in producing mesothelioma; the percentages were different between groups and untreated chrysotile but not significantly so. The differences may be explained on the basis of the number of fibers injected which were greater than 8 microns in length and less than 0.25 microns in diameter. The findings of a proficiency of long fibers to produce mesothelioma, previously reported by others for glass fibers, could be applied to chrysotile. PMID- 1313400 TI - Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies. AB - Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 beta carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS-4 and effectively inhibited binding of HRS-4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH-coupled Ab2 beta 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH-coupled 14G9 and 9G10 exhibited a statistically significant (p less than 0.01) delayed-type hypersensitivity reaction against CD30 expressing Hodgkin-derived L540-cells. We conclude from these data that Ab2 beta 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30-specific T-cell- and B-cell-mediated immune response in mice and even across species barriers in rabbits. These CD30 anti-id antibodies may hold promise for use as vaccines against CD30-antigen expressing lymphomas. PMID- 1313401 TI - Differential expression of myogenic regulatory genes, MyoD1 and myogenin, in human rhabdomyosarcoma sublines. AB - A cell line (SCMC-MM-1) was established from a human abdominal tumor that was initially diagnosed as a malignant mesenchymoma by histological, immunohistochemical and clinical criteria. The cell line was composed of 2 morphologically and immunohistochemically distinct cell types, one with a small polygonal phenotype (P-type), characterized by the immunostaining of vimentin and the presence of a few electron-microscopically visible organelles, and the other with a giant tubular phenotype (T-type), characterized by the immunostaining of desmin, alpha-sarcomeric actin and skeletal-muscle myosin, and the presence of thick and thin myofilaments and Z-line materials. The parental cell line was cloned into 2 sublines, a P-type clone (SCMC-MM-1-19P) and a T-type clone (SCMC MM-1-1T), which shared both 2q37 and 11p15 translocations, the characteristic chromosomal aberrations for rhabdomyosarcoma, with the parental SCMC-MM-1 cell line. Northern-blot analyses of the myogenic regulatory genes, including MyoD1 and myogenin, demonstrated the expression of MyoD1 in both of these sublines. Myogenin was very weakly expressed in the SCMC-MM-1-19P subline, but strongly expressed in the SCMC-MM-1-1T subline. Chromosomal and myogenic-regulatory-gene analyses revealed that both of these sublines were rhabdomyosarcoma cell lines. Furthermore, the regulatory-gene analyses indicated that these 2 sublines represented 2 distinct differentiation stages of myoblasts, and that MyoD1 and myogenin could serve as the lineage marker and the differentiation marker, respectively, of human rhabdomyosarcoma. PMID- 1313402 TI - Non-A non-B hepatitis and hepatitis C virus. PMID- 1313403 TI - Regional hyperthermia combined with radiotherapy in the treatment of lung cancers. AB - Twenty locally advanced lung cancers were treated by hyperthermia in combination with radiotherapy between November 1980 and January 1990. All tumors selected had invaded or were in contact with the chest wall, so that transcutaneous insertion of thermal probes into the tumor was possible. Using an 8 or 13.56 MHZ RF capacitive heating device, hyperthermia was given once or twice a week after irradiation for 30-60 min per session (1-12 sessions in total). Radiotherapy was delivered at dose of 13.6-70 Gy. The thermal parameters analyzed were a) maximum, average, and minimum intratumor temperatures (Tmax, Tav, and Tmin), which were recorded at the termination of each treatment, and b) the percentages of the intratumor points that exceeded 41 C (%T greater than or equal to 41 C). The mean +/- SD for Tmax, Tav, Tmin, and %T greater than or equal to 41 C was 42.9 +/- 1.7 C, 41.6 +/- 1.2 C, 39.7 +/- 1.1 C, and 56.2 +/- 25.8, respectively. Larger tumors showed higher thermal parameters than the smaller tumors. Of the 12 tumors treated by definitive therapy, 2 (17%) achieved CR, 7 (58%) PR, and 3 (25%) NR. Four of 10 tumors that did not achieve CR showed large intratumor low density areas on post-treatment CT, reflecting massive coagulation necrosis. Higher thermal parameters were closely related to the appearance of low-density areas but not to changes in tumor size. Four tumors treated preoperatively were successfully resected 2 weeks after thermoradiotherapy, whereas four palliatively treated tumors showed no regression. The side effects associated with hyperthermia were pain in 12 patients (60%) and dyspnea in 3 (15%), all of which resolved after termination of treatment. A skin abscess and a pneumothorax attributed to thermal probe insertion were observed in one patient each. These results indicate that regional RF capacitive hyperthermia is clinically feasible for local treatment of selected lung cancers. PMID- 1313404 TI - Response to Choi's "Controversies in the role of postoperative radiotherapy in stages II and IIIA resected non-small cell lung carcinoma". PMID- 1313405 TI - Prognostic assessment of tumor regression after external irradiation for cervical cancer. AB - From February 1980 to December 1986, 428 cases of cervical cancer in Stage I through IVA were given curative radiation therapy at Chang Gung Memorial Hospital, Taipei. All of them received external irradiation and intracavitary brachytherapy. The degree of tumor regression was assessed immediately before the first intracavitary brachytherapy treatment. Patients were classified at this time as having (a) no gross residual tumor, or (b) gross residual tumor. Factors found to be associated with tumor regression by logistic regression analysis were stage, age and hemoglobin level. Patients with advanced cancer (Stage III, IVA), young age (less than 40 years), and low hemoglobin level (less than 10 g/dl) had a low incidence of no gross residual tumor. Five-year survival rate was 77% in patients with no gross residual tumor and 31% in patients with gross residual tumor (p less than 0.001). This significant difference held true even when one compared these two groups stage for stage; the difference was 77% versus 41% (p less than 0.001) in Stage II and 72% versus 28% (p less than 0.001) in Stage III. The local relapse rate was 59% in the gross residual tumor groups, significantly greater (p less than 0.001) than the 12% found in the no gross residual tumor group. It was concluded that patients whose tumors did not regress after external pelvic irradiation tended to recur after intracavitary brachytherapy, most often locally. This would justify a more aggressive treatment to improve local tumor control in this subset of high risk patients. PMID- 1313406 TI - Chemodectoma of the head and neck: results of treatment in 84 patients. AB - Eighty-four patients with chemodectoma of the head and neck presented to the Royal Marsden Hospital between 1949 and 1985. For tumors arising at the skull base (glomus jugulare and glomus tympanicum) 46 were treated with radiotherapy alone resulting in an actuarial local control rate of 73% at 25 years; 13 were treated with surgery plus radiotherapy with no recurrences during a median follow up of 9 years; 4 had surgery alone but all recurred by 7 years. For tumors of the soft tissues of the neck (carotid body and glomus vagale) 13 were treated with surgery alone with an actuarial control rate of 54% at 15 years; 4 were treated with radiotherapy which resulted in local control at 1, 2, 8 and 11 years; and one patient who received both surgery and radiotherapy remained controlled at 1 year. Although comparison between radiotherapy and surgery in terms of tumor control is not simple, the case is argued for more frequent use of radiotherapy at all sites. This case is strengthened by minimal morbidity from radiotherapy in doses which appear effective: in the range of 45-50 Gy in 25 daily fractions over 5 weeks. PMID- 1313407 TI - Radiotherapy for pleomorphic adenoma of the parotid gland. AB - A study was made of 187 patients with parotid pleomorphic adenoma treated by radiotherapy. This followed surgery but with incomplete removal or tumor spillage. In the early years of the study radiotherapy was given by radium needle implant done usually at the time of surgery, but from the late 1960s beam directed external radiotherapy with a head shell was used most commonly. A 3 field technique or wedge pair was the standard technique. The median age was 46 with nearly half the patients (87/187) aged between 40 and 60, and the ratio of women to men was 1.4:1 (110:77). Median follow-up for all patients was 14 years. One hundred fifteen patients had radiotherapy immediately after their first operation with a recurrence rate of 0.9% (1/115). Of the 115 there were 2 cases of radionecrosis (1 major, 1 minor), 1 case of permanent facial nerve palsy, 1 Frey Syndrome (post-gustatory sweating), and 1 salivary fistula. Seventy-two patients had radiotherapy delayed until one or more recurrences had been surgically treated. Nine (12.5%) of these developed yet further recurrence after radiotherapy. There were 2 cases of radionecrosis (1 major), 4 cases of facial nerve palsy (3 of which were complete), 16 cases (22.2%) of Frey Syndrome, and 1 case of malignant change in a parotid tumor. In addition one squamous cell carcinoma developed at the site of a needle implant 25 years later. Recurrences after radiotherapy continued beyond 20 years of follow-up. Patients having unsatisfactory surgery due to spill at operation or residual tumor left behind should have radiotherapy immediately and not delayed until local recurrence occurs because of the increased morbidity and the higher incidence of yet further recurrence. PMID- 1313408 TI - Detection of Epstein-Barr virus DNA in a Japanese case of lymphoepithelioma-like thymic carcinoma. AB - Epstein-Barr virus DNA was detected in a case of lymphoepithelioma-like thymic carcinoma. A homogeneous terminal structure of the viral DNA was demonstrated in this case, indicating the presence of the viral genome in clonally expanded tumor cells. Since all of 26 other thymic epithelial tumors (eight non-invasive, 13 invasive thymomas and four non-lymphoepithelioma-like thymic carcinomas) in Japanese were negative by polymerase chain reaction, it is suggested that lymphoepithelioma-like thymic carcinoma may represent a unique pathological entity distinct from Epstein-Barr virus-negative thymic epithelial tumors, which are in the majority in Japan. PMID- 1313409 TI - Quartromicin, a complex of novel antiviral antibiotics. I. Production, isolation, physico-chemical properties and antiviral activity. AB - A strain of Amycolatopsis orientalis No. Q427-8 (ATCC 53884) was found to produce a complex of new antiviral antibiotics, quartromicin which consisted of at least six components A1, A2, A3, D1, D2 and D3. Structural studies suggested that they are a novel type of molecules unrelated to any known antibiotics. Each component of quartromicin exhibited antiviral activity against herpes simplex virus type 1, influenza virus type A and human immunodeficiency virus. PMID- 1313410 TI - Protective effects of immunoactive peptide, FK565 against systemic and local infections with herpes simplex virus and murine cytomegalovirus and respiratory tract infection with influenza virus in mice. AB - The protective effects of FK565 against systemic infections with herpes simplex virus (HSV) and murine cytomegalovirus (MCMV), respiratory tract infection with influenza virus and zosteriform rash with HSV investigated in mice. FK565 showed excellent protective activities against systemic infections with both acyclovir (ACV)-sensitive and -resistant HSV at intravenous and subcutaneous doses of 0.1 and 1 mg/kg and oral dose of 1 mg/kg. FK565 showed superior protective activities at subcutaneous doses of 0.01 and 0.1 mg/kg compared to ACV at subcutaneous dose of 15 mg/kg against MCMV infection. In respiratory tract infection with influenza virus, FK565 showed potent protective effects at intravenous, subcutaneous and oral doses of 0.001 to 1 mg/kg. FK565 markedly inhibited zosteriform spread of HSV on the flank skin at an intravenous dose of 0.1 mg/kg and the mice given FK565 survived longer than the control mice. The peritoneal exudate cells from FK565-treated mice suppressed the growth of HSV in mouse embryo fibroblast more strongly than those from the control mice, although FK565 had no direct antiviral activity against HSV. These findings suggest that FK565 enhanced the host defense ability against viral infections by nonspecific activation of macrophages. PMID- 1313411 TI - Use of gene probes based on the insertion sequence IS986 to differentiate between BCG vaccine strains. AB - Gene probes derived from the insertion sequence IS986, which have previously been shown to differentiate isolates of Mycobacterium tuberculosis for epidemiological analysis, are also capable of distinguishing two groups of BCG vaccine strains. Most BCG strains have a single copy of IS986, at the same chromosomal site, while the Brazilian, Japanese and USSR strains have an additional copy at a different, common location. These results correlate with the results of previous antigenic analysis and may reflect a different clonal origin of the two groups of BCG strains. PMID- 1313412 TI - Cell density-dependent modulation of the Vibrio fischeri luminescence system in the absence of autoinducer and LuxR protein. AB - Expression of the Vibrio fischeri luminescence genes (luxR and luxICDABEG) in Escherichia coli requires autoinducer (N-3-oxohexanoyl homoserine lactone) and LuxR protein, which activate transcription of luxICDABEG (genes for autoinducer synthase and the luminescence enzymes), and cyclic AMP (cAMP) and cAMP receptor protein (CRP), which activate transcription of the divergently expressed luxR gene. In E. coli and in V. fischeri, the autoinducer-LuxR protein-dependent induction of luxICDABEG transcription (called autoinduction) is delayed by glucose, whereas it is promoted by iron restriction, but the mechanisms for these effects are not clear. To examine in V. fischeri control of lux gene expression by autoinducer, cAMP, glucose, and iron, lux::Mu dI(lacZ) and lux deletion mutants of V. fischeri were constructed by conjugation and gene replacement procedures. beta-Galactosidase synthesis in a luxC::lacZ mutant exhibited autoinduction. In a luxR::lacZ mutant, complementation by the luxR gene was necessary for luminescence, and addition of cAMP increased beta-galactosidase activity four- to sixfold. Furthermore, a luxI::lacZ mutant produced no detectable autoinducer but responded to its addition with induced synthesis of beta-galactosidase. These results confirm in V. fischeri key features of lux gene regulation derived from studies with E. coli. However, beta-galactosidase specific activity in the luxI::lacZ mutant, without added autoinducer, exhibited an eight- to tenfold decrease and rise back during growth, as did beta galactosidase and luciferase specific activities in the luxR::lacZ mutant and luciferase specific activity in a delta(luxR luxICD) mutant. The presence of glucose delayed the rise back in beta-galactosidase and luciferase specific activities in these strains, whereas iron restriction promoted it. Thus, in addition to transcriptional control by autoinducer and LuxR protein, the V. fischeri lux system exhibits a cell density-dependent modulation of expression that does not require autoinducer, LuxR protein, or known lux regulatory sites. The response of autoinducer-LuxR protein-independent modulation to glucose and iron may account for how these environmental factors control lux gene expressions. PMID- 1313413 TI - Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions. AB - Helicobacter pylori produces a potent urease that is believed to play a role in the pathogenesis of gastroduodenal diseases. Four genes (ureA, ureB, ureC, and ureD) were previously shown to be able to achieve a urease-positive phenotype when introduced into Campylobacter jejuni, whereas Escherichia coli cells harboring these genes did not express urease activity (A. Labigne, V. Cussac, and P. Courcoux, J. Bacteriol. 173:1920-1931, 1991). Results that demonstrate that H. pylori urease genes could be expressed in E. coli are presented in this article. This expression was found to be dependent on the presence of accessory urease genes hitherto undescribed. Subcloning of the recombinant cosmid pILL585, followed by restriction analyses, resulted in the cloning of an 11.2-kb fragment (pILL753) which allowed the detection of urease activity (0.83 +/- 0.39 mumol of urea hydrolyzed per min/mg of protein) in E. coli cells grown under nitrogen limiting conditions. Transposon mutagenesis of pILL753 with mini-Tn3-Km permitted the identification of a 3.3-kb DNA region that, in addition to the 4.2-kb region previously identified, was essential for urease activity in E. coli. Sequencing of the 3.3-kb DNA fragment revealed the presence of five open reading frames encoding polypeptides with predicted molecular weights of 20,701 (UreE), 28,530 (UreF), 21,744 (UreG), 29,650 (UreH), and 19,819 (UreI). Of the nine urease genes identified, ureA, ureB, ureF, ureG, and ureH were shown to be required for urease expression in E. coli, as mutations in each of these genes led to negative phenotypes. The ureC, ureD, and ureI genes are not essential for urease expression in E. coli, although they belong to the urease gene cluster. The predicted UreE and UreG polypeptides exhibit some degree of similarity with the respective polypeptides encoded by the accessory genes of the Klebsiella aerogenes urease operon (33 and 92% similarity, respectively, taking into account conservative amino acid changes), whereas this homology was restricted to a domain of the UreF polypeptide (44% similarity for the last 73 amino acids of the K. aerogenes UreF polypeptide). With the exception of the two UreA and UreB structural polypeptides of the enzyme, no role can as yet be assigned to the nine proteins encoded by the H. pylori urease gene cluster. PMID- 1313414 TI - Ty insertions upstream and downstream of native DUR1,2 promoter elements generate different patterns of DUR1,2 expression in Saccharomyces cerevisiae. AB - Expression of allantoin pathway genes is subject to induction and nitrogen catabolite repression. Two classes of cis-dominant mutations (DUR80 and DUR1,2 Oh) result in overproduction of DUR1,2 mRNA. In DUR80 mutants, DUR1,2 expression remained inducible, nitrogen catabolite repression sensitive, and unresponsive to cell ploidy, i.e., overproduction was superimposed on normal gene regulation. DUR1,2-Oh mutations, in contrast, generated a pattern of DUR1,2 expression similar to that often reported when a Ty element inserts upstream of a gene, the ROAM phenotype. We analyzed four independent DUR80 and DUR1,2-Oh alleles. The DUR1,2-Oh mutation was, as expected, a Ty insertion at -445 3' of the native DUR1,2 upstream activation sequences (UASs). All three DUR80 alleles were also Ty insertions between -644 and -653 immediately 5' of the native DUR1,2 USASs. We suggest that the difference in DUR1,2-Oh and DUR80 phenotypes depends on whether the native cis-acting elements and transcription factors associated with them can operate. If they can, enhancement of normally regulated DUR1,2 expression is observed. This is a novel phenotype for Ty insertions. If the native DUR1,2 cis acting elements are not present, the case when Ty insertion occurs 3' of them, a ROAM phenotype is generated. Nitrogen-regulated upstream activation sequence (UASNTR)-homologous sequences present in the Ty delta elements rather than cis acting elements required for Ty transcription are the most likely candidates to serve as the cis-acting elements mediating the DUR80 phenotype. PMID- 1313415 TI - Cloning and characterization of a gene required for the secretion of extracellular enzymes across the outer membrane by Xanthomonas campestris pv. campestris. AB - Nonpathogenic mutants of Xanthomonas campestris pv. campestris, generated from transposon mutagenesis, accumulated extracellular polygalacturonate lyase, alpha amylase, and endoglucanase in the periplasm. The transposon Tn5 was introduced by a mobilizable, suicidal plasmid, pSUP2021 or pEYDG1. Genomic banks of wild-type X. campestris pv. campestris, constructed on the broad-host-range, mobilizable cosmid pLAFR1 or pLAFR3, were conjugated with one of the mutants, designated XC1708. Recombinant plasmids isolated by their ability to complement XC1708 can be classified into two categories. One, represented by pLASC3, can complement some mutants, whereas the other, represented by a single plasmid, pLAHH2, can complement all of the other mutants. Restriction mapping showed that the two recombinant plasmids shared an EcoRI fragment of 8.9 kb. Results from subcloning, deletion mapping, and mini-Mu insertional mutation of the 8.9-kb EcoRI fragment suggested that a 4.2-kb fragment was sufficient to complement the mutant XC1708. Sequence analysis of this 4.2-kb fragment revealed three consecutive open reading frames (ORFs), ORF1, ORF2, and ORF3. Hybridization experiments showed that Tn5 in the genome of XC1708 and other mutants complemented by pLASC3 was located in ORF3, which could code for a protein of 83.5 kDa. A signal peptidase II processing site was identified at the N terminus of the predicted amino acid sequence. Sequence homology of 51% was observed between the amino acid sequences predicted from ORF3 and the pulD gene of Klebsiella species. PMID- 1313416 TI - Cyclic nucleotide-binding domains in proteins having diverse functions. PMID- 1313417 TI - Detection of lipid radicals by electron paramagnetic resonance spin trapping using intact cells enriched with polyunsaturated fatty acid. AB - Electron paramagnetic resonance (EPR) spin trapping was used to detect lipid derived free radicals generated by iron-induced oxidative stress in intact cells. Using the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), carbon centered radical adducts were detected. These lipid-derived free radicals were formed during incubation of ferrous iron with U937 cells that were enriched with docosahexaenoic acid (22:6n-3). The EPR spectra exhibited apparent hyperfine splittings characteristic of a POBN/alkyl radical, aN = 15.63 +/- 0.06 G and aH = 2.66 +/- 0.03 G, generated as a result of beta-scission of alkoxyl radicals. Spin adduct formation depended on the FeSO4 content of the incubation medium and the number of 22:6-enriched cells present; when the cells were enriched with oleic acid (18:1n-9), spin adducts were not detected. This is the first direct demonstration, using EPR, of a lipid-derived radical formed in intact cells in response to oxidant stress. PMID- 1313418 TI - Identification of cysteine-rich domains of the type 1 tumor necrosis factor receptor involved in ligand binding. AB - The extracellular portion of the type 1 (p55) and type 2 (p75) tumor necrosis factor (TNF) receptors contains a repetitive amino acid sequence pattern of four cysteine-rich domains (CRDs). This pattern is found also in several other cell surface proteins, including the p75 nerve growth factor receptor and the CD40, 4 1BB, OX40, Fas, and CD27 antigens. To investigate whether CRDs play a role in TNF binding, we have constructed soluble variants of the extracellular portion of human type 1 TNF receptor (sTNFR1), in which CRD1 (N-terminal) or CRD4 (C terminal) was deleted by mutagenesis. These variants or a wild type sTNFR1 were linked in their C terminus to the hinge and Fc portion of IgG1 heavy chain to create sTNFR1-IgG chimeras (immunoadhesins). Deletion of either CRD1 or -4 did not cause any major perturbations in the structure of the sTNFR1 variants, as evidenced by their efficient expression and secretion from transfected cells, and by their binding to conformation-dependent monoclonal antibodies that recognize diverse epitopes on sTNFR1. The wild type sTNFR1 immunoadhesin exhibited high affinity binding to TNF alpha (Kd = 65 pM) and TNF beta (Kd = 640 pM). Deletion of CRD4 resulted in about a 10-fold reduction in affinity for TNF alpha (Kd = 660 pM) and for TNF beta (Kd = 5.7 nM). In contrast, deletion of CRD1 resulted in a complete loss of binding to TNF alpha and to TNF beta. These results indicate that CRD4 is important but not necessary for TNF binding, while CRD1 is required. In addition, the results suggest some overlap between the TNFR1 binding sites for TNF alpha and TNF beta, despite low amino acid sequence homology between these cytokines. PMID- 1313420 TI - rab15, a novel low molecular weight GTP-binding protein specifically expressed in rat brain. AB - rab3A is a low molecular weight (LMW) GTP-binding protein specifically expressed in brain and localized to synaptic vesicles. rab3A has been proposed to play a role in neurotransmitter release by regulating membrane flow in the nerve terminal. In an attempt to define other LMW GTP-binding proteins that may regulate neurotransmitter release, seven cDNA clones encoding new members of the rab family of LMW GTP-binding proteins were isolated from a rat brain cDNA library. The rab proteins contain the four conserved structural domains essential for GTP binding in addition to domains required for membrane localization and effector protein interactions. One protein, rab16, is closely related to members of the rab3 subfamily, whereas two others are assigned as the rat homologs of canine rab8 and rab10. Four additional clones, rab12, rab13, rab14, and rab15, revealed unique sequences and are new members of the rab family of LMW GTP binding proteins. The patterns of expression of rab15 and rab3A closely overlap but differ from that observed for all other known LMW GTP-binding proteins. This data suggests that rab15 may act in concert with rab3A in regulating aspects of synaptic vesicle membrane flow within the nerve terminal. PMID- 1313421 TI - Examination of the functional roles of 5 highly conserved residues in the cytochrome b subunit of the bc1 complex of Rhodobacter sphaeroides. AB - The cytochrome b subunit of the bc1 complexes contains two cytochrome components (bL and bH) and is the locus of both a quinol-oxidizing site (Qo or Qz) and a quinone-reducing site (Qi or Qc). Sequence alignments of this subunit from over 20 eukaryotic and prokaryotic species have revealed a remarkable degree of conservation, including approximately 20 totally conserved residues. In this paper, site-directed mutagenesis has been used to examine the structural or functional roles of 5 of these highly conserved residues, Gly48, Gln58, Ser102, Phe104, and Pro202, all predicted to be within transmembrane alpha-helical segments. The mutants were made in the bc1 complex of Rhodobacter sphaeroides, a photosynthetic bacterium. The ability to use spectroscopic, electrochemical, and flash-induced kinetic methods allows the mutants to be analyzed for influences both on cytochrome spectra and thermodynamic properties and on the kinetics of specific electron transfer reactions. The results show that none of the 5 residues is absolutely essential. Substitution of aspartate or valine for Gly48 results in the loss of photosynthetic growth. The G48V mutant assembles a bc1 complex, but with modified cytochromes bH and bL, and a dysfunctional quinone reductase (Qc) site; an alanine is tolerated at this position. Possibly, a small residue is important here for heme packing. Gln58 and Ser102 are the only highly conserved polar residues predicted to be within the transmembrane spans, apart from the histidines which are heme axial ligands. Neither Gln58 nor Ser102 is essential for assembly or function of the bc1 complex, although substitution of other amino acids in these positions does cause subtle, but measurable changes. Phe104 lies midway between the axial ligands to cytochromes bL and bH and can be modeled to project in the space separating the two hemes. Replacement of this highly conserved aromatic residue by isoleucine has no measurable influence on the rate of electron transfer through the cytochrome b chain containing the two hemes. Finally, Pro202 is a totally conserved proline which is in the middle of transmembrane helix D, in between the 2 histidines which provide ligands to the hemes. No major inhibition of electron transfer resulted from replacing this proline by a leucine, although subtle changes in spectra of the b cytochromes and their electrochemical properties were noted. PMID- 1313422 TI - The effect of histidine modification on the activity of myo-inositol monophosphatase from bovine brain. AB - The pH dependence of myo-inositol monophosphatase may indicate a role for histidine residues in the catalytic mechanism (Ganzhorn, A. J., and Chanal, M.-C. (1990) Biochemistry 29, 6065-6071). This possibility was investigated by chemical modification. At pH 6.0 and 25 degrees C, the enzyme was inactivated by diethylpyrocarbonate in a pseudo-first order reaction with a bimolecular rate constant of 0.37 M-1 s-1. Two histidines were modified rapidly with no effect on enzyme activity, while 3 residues were modified at a slower rate corresponding to the rate of inactivation. No noticeable changes in the secondary structure of the enzyme were observed by comparison of circular dichroic spectra before and after modification. Treatment of myo-inositol monophosphatase with diethylpyrocarbonate in the presence of inositol 1-phosphate, Mg2+, and Li+ protected 2 residues from modification and decreased the inactivation rate by about 5-fold. Spectrophotometric analysis, the restoration of enzyme activity by hydroxylamine, and the lack of any inhibitory effect with alkylating agents suggest that inactivation is due solely to modification of histidine. We conclude that a histidine residue is essential for activity and may act as a base catalyst during hydrolysis of the substrate. PMID- 1313419 TI - Phospholipid base exchange activity in rat liver plasma membranes. Evidence for regulation by G-protein and P2y-purinergic receptor. AB - Phospholipid base exchange activity using choline as substrate was detected in plasma membranes (PM) and other subcellular fractions of rat liver, with microsomes (MS) showing the highest specific activity. In contrast, phospholipase D activity was only detected in PM. In PM, choline exchanged for phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), whereas ethanolamine exchanged for PE and PS, and serine exchanged for PS. Ca2+ (10 microM or higher) stimulated choline incorporation into PC in MS and PM, whereas Mg2+ (10 microM or higher) stimulated it only in PM. Ethanolamine and serine incorporation into PM phospholipids was also stimulated by Ca2+, and inositol incorporation by Mn2+. Phospholipase D activity was substantial in the presence of EGTA and was slightly stimulated by Ca2+ concentrations less than 500 microM. It was undetectable without Mg2+. Low concentrations of oleate (1 mM or less) stimulated phospholipase D activity. These concentrations inhibited choline base exchange activity, whereas higher concentrations (3-8 mM) were stimulatory. Comparison of the subcellular distribution and Ca2+, Mg2+, and oleate effects on choline base exchange and phospholipase D activities supports the view that they are catalyzed by different enzymes. The incorporation of choline, but not ethanolamine or serine, into the phospholipids of PM, but not MS, was stimulated by micromolar concentrations of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) and other slowly hydrolyzable analogues of GTP. GDP, GMP, and other nucleoside triphosphates and their analogues were ineffective. GTP gamma S stimulation of base exchange activity was dependent upon Mg2+ and was inhibited by high concentrations of guanosine 5'-O-2-(thio)diphosphate. In the presence of low concentrations of GTP gamma S, ATP and its slowly hydrolyzable analogues stimulated base exchange activity. Dose-response curves for these nucleotides revealed a potency order consistent with mediation by purinergic receptors of the P2Y type. Base exchange activity stimulated by ATP plus GTP gamma S or GTP gamma S alone was not altered by treatment with pertussis or cholera toxins. These results suggest that the choline base exchange activity of liver PM is regulated by a pertussis toxin-insensitive G-protein linked to P2Y purinergic receptors. PMID- 1313423 TI - Calcium-induced inhibition of phosphoserine phosphatase in insulin target cells is mediated by the phosphorylation and activation of inhibitor 1. AB - In this study, we examined the mechanism of inhibition of phosphoserine phosphatase (PSPase) activity by elevated [Ca2+]i in insulin target cells. In in vitro studies, isolated rat adipocytes were incubated with either 40 mM K+ or parathyroid hormone (PTH) (20 ng/ml) for 1 h. In in vivo studies, rats were injected with PTH (three hourly injections of 40 micrograms intraperitoneally) prior to isolation of either adipocytes or skeletal muscle. Under these conditions, intracellular [Ca2+]i changed from 100 +/- 8.7 to 263 +/- 10.5 nM. There was a concomitant 30% decrease in adipocyte PSPase activity and a 35% decrease in skeletal muscle PSPase activity, assayed using 32P-labeled phosphorylase "a" as a substrate. The inhibition of PSPase was accompanied by a 60% increase in adipocytes (p less than 0.05) and a 118% increase (p less than 0.01) in skeletal muscle inhibitor 1 (I1) activities, respectively. Since I1 is active only in the phosphorylated state, we studied the effect of [Ca2+]i on I1 phosphorylation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of heat treated extracts immunoprecipitated with I1 antibody revealed significant increase in 32P incorporation (45-60%, p less than 0.05) into I1 protein in cells with elevated [Ca2+]i. Nitrendipine, a calcium channel blocker, completely prevented increases in I1 phosphorylation and activity in cells exposed to K+ but was only partially effective in the PTH-treated cells. In contrast, a cyclic AMP antagonist, RpcAMP, prevented both the K(+)-and the PTH-induced increases in I1 phosphorylation and activity, even though it failed to block the elevations in [Ca2+]i in these cells. We conclude that [Ca2+]i-induced and cAMP-mediated phosphorylation and activation of I1 results in inhibition of PSPase activity in insulin target cells. The inhibition of PSPases may cause inappropriate serine dephosphorylation of substrates of insulin action resulting in insulin resistance. PMID- 1313424 TI - Salivary statherin. Dependence on sequence, charge, hydrogen bonding potency, and helical conformation for adsorption to hydroxyapatite and inhibition of mineralization. AB - The structural domains of salivary statherin that are partly responsible for the protection and recalcification of tooth enamel were examined with respect to charge, sequence, hydrophobicity, hydrogen bonding potential, and conformation. Several fragments of statherin, 1-15 (SN15), 5-15 (SN11), 15-29 (SM15), 29-43 (SC15), 19-43 (SC25), and analogs of the N-terminal 15-residue sequence, where phosphoserines at positions 2 and 3 have been replaced by Ser (SNS15) and Asp (SNA15), respectively, were synthesized. The abilities of these fragments to adsorb at hydroxyapatite (HAP) surfaces and to inhibit its mineralization in supersaturated solutions were determined and compared with those of the whole statherin molecule, reported previously. The conformational preferences of the fragments both in aqueous and nonaqueous solutions were examined by circular dichroism. The highly charged N-terminal SN15 fragment has the greatest adsorption to HAP as compared with statherin and all other fragments. Its mineralization inhibitory activity is significantly greater than those of other fragments and comparable with that of the whole molecule. The dephosphorylated N terminal fragment SNS15 shows a decreased tendency to adhere to and inhibit the formation of HAP, as compared with SN15. However, the substitution of Asp residues in place of phosphoserines (SNA15), restores the binding affinity and crystal growth inhibition properties, suggesting that the negative charge density at the N-terminal rather than any specific interaction of the phosphate group is important for HAP surface interactions. The C-terminal SC15 and SC25 fragments elicit a much higher affinity for HAP surface than that of the middle sequence (SM15), indicating that hydrogen bonding potential of the C-terminal sequence also contributes to the interaction of statherin with HAP. CD studies provide evidence that the N-terminal SN15 fragment has a strong tendency to adopt an ordered helical conformation, whereas the shorter N-terminal sequence, middle, and C-terminal fragments are structurally flexible and prefer to adopt scattered turn structures or unordered random conformations in organic and aqueous solutions. Collectively, the data indicate that the negative charge density, sequence (1-15), and helical conformation at the N-terminal region of statherin are important for its surface interaction with HAP. PMID- 1313425 TI - Peptide sequences from the hypervariable regions of two monoclonal anti-idiotypic antibodies against the thyrotropin (TSH) receptor are similar to TSH and inhibit TSH-increased cAMP production in FRTL-5 thyroid cells. AB - Monoclonal antibodies, D2 and 4G11, selected by the autoantiidiotypic approach following injection of thyrotropin (TSH) into mice, mimic TSH in binding to receptors on thyroid membranes. Based on TSH receptor transfection studies, D2 and 4G11 show unequivocal specificity for the TSH receptor. To see if the complementary determining regions (CDRs) of these antibodies share any primary sequence similarities to regions of TSH critical for receptor binding, we deduced the primary structure of the variable regions of D2 and 4G11 by sequencing the immunoglobulin mRNA. We found that CDR1 of 4G11K and CDR2 of D2 mu show sequence similarity to regions of TSH alpha and TSH beta that had been previously implicated in the interaction of the hormone with its receptor. We tested the inhibitory effects of synthetic peptides from D2 mu-CDR2 and 4G11K-CDR1 on the binding of the corresponding antibodies to rat thyroid FRTL-5 cells and found an EC50 of 0.1 and 1 microM, respectively. TSH-derived peptides with similarity to D2 mu-CDR2 and 4G11K-CDR1 showed a significant but lesser effect on the binding of 4G11 or D2 to thyroid cells. Additionally, we tested the effects of the CDR peptides and TSH-derived peptides on TSH-stimulated cAMP production in FRTL-5 cells and found that D2 mu-CDR2 and 4G11K-CDR1 inhibited this activity, D2 mu CDR2 most strongly (EC50 10 microM). Thus, linear sequences from the CDRs of these autoantiidiotypic antibodies with similarity to sequences from both subunits of TSH appear to interact with the TSH receptor. These data support previous studies indicating the complexity of the interaction between TSH and its receptor and advance earlier findings that such immunologic approaches are useful in dissecting receptor-ligand interactions. PMID- 1313427 TI - Four different DNA helicases from calf thymus. AB - Using a strand displacement assay we have followed DNA helicase activities during the simultaneous isolation of several enzymes from calf thymus such as DNA polymerases alpha, delta, and epsilon, proliferating cell nuclear antigen, and replication factor A. Thus we were able to discriminate and isolate four different DNA helicases called A, B, C, and D. DNA helicase A is identical with the enzyme described earlier (Thommes, P., and Hubscher, U. (1990) J. Biol. Chem. 265, 14347-14354). The four enzymes can be distinguished by (i) their putative molecular weights after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (ii) glycerol gradient sedimentation under low and high salt conditions, (iii) sensitivity to salt, (iv) binding to DNA, (v) nucleoside- and deoxynucleoside 5'-triphosphate requirements, and (vi) by their direction of movement. DNA helicase A unwinds in the 3'----5' direction on the DNA it was bound to, while DNA helicases B, C, and D do so in the 5'----3' direction. DNA helicase D, and to some extent DNA helicases B and C, are able to unwind long substrates of more than 400 nucleotides. Replication factor A, a single-stranded heterotrimeric DNA binding protein involved in cellular DNA replication and DNA repair stimulates the DNA helicases. The stimulatory effect is most pronounced on DNA helicase A, where replication factor A enables this helicase to unwind longer substrates. DNA helicases B, C, and D are also stimulated by replication factor A. The effect of replication factor A appears to be specific since corresponding single-stranded DNA binding proteins from Escherichia coli and bacteriophage T4 have no or even a negative effect on the four DNA helicases. Heterologous human replication factor A has no stimulatory effect on any of the four DNA helicases suggesting a species specificity of these interactions. Thus it appears that mammalian cells possess, as does E. coli, a variety of different enzymes that can transiently abolish the double helical DNA structure in the cell. PMID- 1313426 TI - Homologous desensitization of HEL cell thrombin receptors. Distinguishable roles for proteolysis and phosphorylation. AB - Loss of sensitivity to thrombin following an initial response is characteristic of a number of cell types, including platelets. It has recently been proposed that thrombin receptors resemble other G protein-coupled receptors, but that activation involves a novel mechanism in which thrombin cleaves the receptor, exposing a new N terminus that serves as the ligand for the receptor. Based upon this model, we have examined the mechanism of thrombin receptor desensitization by comparing the effects of thrombin with those of a peptide corresponding to the N-terminal sequence of the receptor following proteolysis by thrombin: SFLLRNPNDKYEPF or TRP42/55. Like thrombin, TRP42/55 stimulated pertussis toxin sensitive inositol 1,4,5-trisphosphate formation, raised cytosolic Ca2+, and inhibited cAMP formation in the megakaryoblastic HEL cell line. Exposure to either thrombin or TRP42/55 desensitized the cells to both, but not to a third agonist, neuropeptide Y. The rate of recovery after desensitization depended upon the order of agonist addition. Resensitization of the cell to thrombin following a brief exposure to thrombin required up to 24 h and could be inhibited with cycloheximide. Resensitization to TRP42/55 after exposure to thrombin, or to thrombin after exposure to TRP42/55, on the other hand, was detectable within 30 min and could be inhibited by serine/threonine phosphatase inhibitors, but not by cycloheximide. Loss of responsiveness to thrombin and TRP42/55 was also observed following addition of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). However, while the protein kinase inhibitor staurosporine completely prevented the desensitization caused by TPA, it had only a limited effect on the desensitization caused by TRP42/55. These results demonstrate that the G protein mediated effects of thrombin can be reproduced by a receptor-derived peptide and suggest that desensitization occurs by at least two mechanisms. The first, which is seen with thrombin, but not TRP42/55, involves proteolysis and requires protein synthesis for recovery. The second, which occurs with TRP42/55 and TPA, as well as with thrombin, involves phosphorylation, possibly of the receptor itself. Although protien kinase C is activated by thrombin and is presumably responsible for the desensitization caused by TPA, it does not appear to play a major role in receptor desensitization caused by thrombin and TRP42/55. This suggests that other kinases, such as those which inactivate adrenergic receptors and rhodopsin, are involved in the down-regulation of thrombin receptor function. PMID- 1313428 TI - Stimulation by growth hormone of MAP kinase activity in 3T3-F442A fibroblasts. AB - We have previously demonstrated that growth hormone (GH) promotes an increase in tyrosine kinase activity associated with the GH receptor. To gain insight into the role of GH-dependent tyrosine kinase activity in signaling by GH, we investigated the possibility that GH might stimulate MAP kinase, a serine/threonine/tyrosine kinase thought to be a common element in tyrosine kinase-initiated response cascades. Treatment of 3T3-F442A fibroblasts with 100 ng/ml GH results in a 3-6-fold increase in the ability of cell-free extracts to phosphorylate MAP-2 and myelin basic protein. GH-stimulated kinase activity is unaffected by heparin, H7, or cAMP-dependent protein kinase inhibitor peptide, partially reduced by staurosporin and inhibited by fluoride and calcium ions, indicating that the kinase is not protein kinase C or A, casein kinase, or a calcium/calmodulin-dependent protein kinase. Based on gel permeation chromatography, the molecular mass of the GH-stimulated MAP kinase is approximately kDa. Furthermore, anti-phosphotyrosine antibodies revealed the GH dependent appearance of two phosphotyrosine-containing proteins in cell-free lysates of GH-treated cells that co-migrate with proteins recognized by anti-MAP kinase antibodies. The GH-dependent increase in MAP kinase activity displays a biphasic time course and is dependent on the concentration of GH applied to the cells. GH-dependent MAP kinase activity, partially purified by Mono-Q chromatography, is inactivated by treatment with alkaline phosphatase. Addition of H7 to the cells prior to the addition of GH has no effect, whereas addition of H8 increases MAP kinase activity in control cells with no effect in GH-treated cells, indicating that protein kinase C is unlikely to be an intermediary in the GH-dependent stimulation of MAP kinase activity. These findings indicate that signaling by GH in 3T3-F443A cells may, at least in part, utilize a kinase cascade similar to those that have been proposed for other membrane receptors with associated tyrosine kinase activity. PMID- 1313429 TI - Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. AB - According to present models, thrombin activates platelets by cleaving its receptors after Arg41, creating a new N terminus which acts as a tethered ligand. In support of this model, a peptide (SFLLRNPNDKYEPF or TRP42/55) corresponding to residues 42-55 has been shown to activate the receptor. In the present studies, the structural basis for thrombin receptor activation was examined using fragments of this peptide, as well as variants of the peptide with selected amino acid substitutions. The results show that the features of SFLLRNPNDKYEPF required to mimic the effects of thrombin reside within the first 6 residues, SFLLRN. A hexapeptide comprised of these residues was approximately 5 times more potent than the parent peptide in assays of platelet aggregation and, in addition, caused tyrosine phosphorylation, inhibition of cAMP formation, and an increase in cytosolic Ca2+. Omission of either the Ser residue or the Arg and Asn residues greatly diminished peptide activity, as did the substitution of Ala for Phe or Arg. Substitution of Ala for Ser or the initial Leu, on the other hand, had little adverse effect. The inactive peptides SALLRN and NPNDKYEPF had no effect on platelet activation initiated by SFLLRN, but FLLRN inhibited platelet aggregation in response to both SFLLRN and thrombin. These results suggest that within SFLLRN the Phe and Arg residues are particularly important and that Phe must be preceded by another amino acid, the identity of which is not tightly constrained. This observation and comparisons with the homologous domains of proteins whose tertiary structure is known were used to predict the conformation of the SFLLR sequence. The model which emerged suggests that the SFLLR domain may be part of an extended beta structure in the intact receptor and that cleavage by thrombin causes it to contract and assume a modified helical configuration. In this predicted conformation the side chains of Phe and Arg point in the same direction, potentially into a pocket formed by the remainder of the receptor. PMID- 1313430 TI - Functional domains of membrane-bound human thrombomodulin. EGF-like domains four to six and the serine/threonine-rich domain are required for cofactor activity. AB - Thrombomodulin is an endothelial cell thrombin receptor that serves as a cofactor for thrombin-catalyzed activation of protein C. Structural requirements for thrombin binding and cofactor activity were studied by mutagenesis of recombinant human thrombomodulin expressed on COS-7 and CV-1 cells. Deletion of the fourth epidermal growth factor (EGF)-like domain abolished cofactor activity but did not affect thrombin binding. Deletion of either the fifth or the sixth EGF-like domain markedly reduced both thrombin binding affinity and cofactor activity. Thrombin binding sequences were also localized by assaying the ability of synthetic peptides derived from thrombomodulin to compete with diisopropyl fluorophosphate-inactivated 125I-thrombin binding to thrombomodulin. The two most active peptides corresponded to (a) the entire third loop of the fifth EGF-like domain (Kp = 85 +/- 6 microM) and (b) parts of the second and third loops of the sixth EGF-like domain (Kp = 117 +/- 9 microM). These data suggest that thrombin interacts with two discrete elements in thrombomodulin. Deletion of the Ser/Thr rich domain dramatically decreased both thrombin binding affinity and cofactor activity and also prevented the formation of a high molecular weight thrombomodulin species containing chondroitin sulfate. Substitutions of this domain with polypeptide segments of decreasing length and devoid of glycosylation sites progressively decreased both cofactor activity and thrombin binding affinity. This correlation suggests that increased proximity of the membrane surface to the thrombin binding site may hinder efficient thrombin binding and the subsequent activation of protein C. Membrane-bound thrombomodulin therefore requires the Ser/Thr-rich domain as an important spacer, in addition to EGF-like domains 4-6, for efficient protein C activation. PMID- 1313431 TI - Inhibition of membrane fusion in vitro via cyclin B but not cyclin A. AB - It is now clear that complexes of cdc2 kinase with "mitotic" cyclins regulate the transition between the G2 phase of the cell cycle and mitosis and that membrane traffic in mammalian cells is arrested during mitosis. Using a cell-free assay, we have previously reported that the fusion of early endosomes is, in fact, inhibited via the cdc2 kinase (Tuomikoski, T., Felix, M.-A., Doree, M., and Gruenberg, J. (1989) Nature 342, 942-945). In the present paper, we show that this in vitro inhibition occurs efficiently only when the kinase activity is specifically evoked by a cyclin of the B-type but not by cyclins of the A-type. In addition, high resolution two-dimensional gel analysis revealed that the kinases associated with A- and B-type cyclins exhibit different substrate preferences. These data suggest that the complexes of the cdc2 kinase with different cyclins may control specific events of the cell cycle. PMID- 1313432 TI - Demonstration of a specific clearance receptor for tissue-type plasminogen activator on rat Novikoff hepatoma cells. AB - The binding, internalization, and degradation of tissue-type plasminogen activator (t-PA) were studied in a rat hepatoma (Novikoff) cell line. Binding of t-PA to specific saturable high affinity binding sites (Kd = 12 nM, 54,000 sites/cell) was followed by internalization and degradation and did not require a functional active site. The catabolism of t-PA was not inhibited by an excess of urokinase-type plasminogen activator (u-PA), and t-PA bound to Novikoff membranes was not complexed to PAI-1, suggesting a mechanism independent of PAI-1. Additionally, a mannose receptor is not involved since t-PA binding was not influenced by an excess of mannose, galactose, ovalbumin, or EDTA. Furthermore, the degradation of t-PA was not influenced by 10 mM 6-aminohexanoic acid, a lysine analogue. The t-PA receptor binds to and can be eluted from wheat germ agglutinin-Sepharose. Cross-linking of t-PA with partially purified receptor and ligand blot analysis, suggest that t-PA binds to two proteins, a principal one of 55 kDa and a minor one of 43 kDa. Novikoff cells are able also to bind (Kd = 1.4 nM, 25,000 sites/cell) and degrade u-PA. The binding was inhibited by pro-u-PA and the amino-terminal fragment of u-PA, but not by an excess of t-PA. The u-PA receptor, but not the t-PA receptor, was removed by treatment with phosphatidylinositol-specific phospholipase C. Our results show that the clearance receptor for t-PA on Novikoff cells is different from the mannose receptor and the PAI-1-dependent receptor described in other cells. The rat hepatoma cells are thus a good model to study the PAI-1 independent hepatocyte specific clearance of t-PA. PMID- 1313433 TI - Study of the cytochrome c2-reaction center interaction by site-directed mutagenesis. AB - Photooxidation of Rhodobacter capsulatus cytochrome c2 and four site-directed mutants by detergent solubilized Rhodobacter sphaeroides reaction centers was studied as a function of ionic strength at pH 8.0. Mutants of cytochrome c2 included K12D (lysine 12 substituted by aspartate), K14E (lysine 14 substituted by glutamate), K32E (lysine 32 substituted by glutamate), and K14E/K32E (lysines 14 and 32 substituted by glutamates). With respect to the wild-type, the mutants exhibited decreased second-order rate constants, indicating perturbation of their electrostatic interaction with the reaction center. In the transient complex, the interaction domain charges of the reaction center and wild-type cytochrome c2 were estimated to be -4.8 and +4.8, respectively. In contrast, the interaction domain charges of mutants K12D, K14E, K32E, and K14E/K32E were estimated to be +2.8, +3.7, +3.6 and +1.3, respectively. At infinite ionic strength, the second order rate constant of the wild-type cytochrome c2 photooxidation (k infinity) was estimated to be 8.7 x 10(6) M-1 s-1. In the case of K32E, k infinity was not changed significantly (8.2 x 10(6) m-1 s-1), suggesting that the electrostatic perturbation of this mutant was largely overcome at high ionic strength. In contrast, the k infinity for K12D, K14E, and K14E/K32E were estimated to be decreased 2-7-fold. Consequently, mutations to R. capsulatus lysines 12 and 14 appear to perturb the distance and/or orientation of the cytochrome c2 relative to the reaction center in the reactive complex, as well as alter electrostatic interactions. Based upon the kinetic results presented here, the cytochrome c2 reaction center transient complex has been modeled. PMID- 1313434 TI - Ligand-induced polyubiquitination of the platelet-derived growth factor beta receptor. AB - We have analyzed the nature of ligand-induced shift to higher molecular weight forms of the beta-receptor for platelet-derived growth factor expressed in porcine aortic endothelial cells. The modification of the beta-receptor was found to be due to polyubiquitination, as judged by immunoblotting using an anti ubiquitin antiserum. A mutant beta-receptor made kinase negative by a point mutation (K634A mutant) did not undergo ubiquitination in response to ligand stimulation. A mutant in which carboxyl-terminal 98 amino acids were deleted (CT98 mutant) and which retained kinase activity was likewise not ubiquitinated. These data suggest that the kinase activity, as well as the carboxyl-terminal 98 amino acids, is required for ubiquitination of the beta-receptor. Ligand-induced degradation of the receptor-bound ligand, as well as of the receptor itself, was partially impaired in the CT98-receptor-expressing cells, suggesting that the ubiquitination is of importance for efficient degradation of the ligand-receptor complex. PMID- 1313435 TI - Effects of antagonists of protein phosphatases on superoxide release by neutrophils. AB - Neutrophils stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) release large quantities of superoxide (O2-) and exhibit phosphorylation of two proteins with molecular masses of 47(p47) and 49 kDa (p49). Addition of inhibitors of protein kinases (e.g. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7)) to these cells after stimulation with PMA results in the loss of 32P from these proteins and a rapid cessation of O2- release (e.g. Heyworth, P. G., and Badwey, J. A. (1990) Biochim. Biophys. Acta 1052, 299-305). In this paper we report that antagonists of type 1 and 2A protein phosphatases (okadaic acid, calyculin A) prevented both the loss of 32P from p47 and the termination of O2- release in stimulated neutrophils treated with H-7. Calyculin A also caused a remarkable hyperphosphorylation of a number of proteins in neutrophils and increased O2- release from these cells in response to a suboptimal amount of PMA. Enzymes present in both the soluble and particulate fractions of neutrophils catalyzed the near complete dephosphorylation of 32P-labeled p47 and p49 bound to Immobilon P membranes. Dephosphorylation of these blotted phosphoproteins occurred at physiological rates and was inhibited by okadaic acid and calyculin A. These data strongly suggest that p47 undergoes a continual cycle of phosphorylation and dephosphorylation throughout the period of O2- release when PMA is the stimulus. Moreover, we show that antagonists of type 1 and 2A protein phosphatases block dephosphorylation of p47 both in vivo and in vitro, indicating that these enzymes may modulate O2- release under certain circumstances. PMID- 1313436 TI - The Caenorhabditis elegans unc-93 gene encodes a putative transmembrane protein that regulates muscle contraction. AB - unc-93 is one of a set of five interacting genes involved in the regulation or coordination of muscle contraction in Caenorhabditis elegans. Rare altered function alleles of unc-93 result in sluggish movement and a characteristic "rubber band" uncoordinated phenotype. By contrast, null alleles cause no visibly abnormal phenotype, presumably as a consequence of the functional redundancy of unc-93. To understand better the role of unc-93 in regulating muscle contraction, we have cloned and molecularly characterized this gene. We isolated transposon insertion alleles and used them to identify the region of DNA encoding the unc-93 protein. Two unc-93 proteins differing at their NH2 termini are potentially encoded by transcripts that differ at their 5' ends. The putative unc-93 proteins are 700 and 705 amino acids in length and have two distinct regions: the NH2 terminal portion of 240 or 245 amino acids is extremely hydrophilic, whereas the rest of the protein has multiple potential membrane-spanning domains. The unc-93 transcripts are low in abundance and the unc-93 gene displays weak codon usage bias, suggesting that the unc-93 protein is relatively rare. The unc-93 protein has no sequence similarity to proteins listed in current data-bases. Thus, unc-93 is likely to encode a novel membrane-associated muscle protein. We discuss possible roles for the unc-93 protein either as a component of an ion transport system involved in excitation-contraction coupling in muscle or in coordinating muscle contraction between muscle cells by affecting the functioning of gap junctions. PMID- 1313437 TI - The signal sequence receptor, unlike the signal recognition particle receptor, is not essential for protein translocation. AB - Detergent extracts of canine pancreas rough microsomal membranes were depleted of either the signal recognition particle receptor (SR), which mediates the signal recognition particle (SRP)-dependent targeting of the ribosome/nascent chain complex to the membrane, or the signal sequence receptor (SSR), which has been proposed to function as a membrane bound receptor for the newly targeted nascent chain and/or as a component of a multi-protein translocation complex responsible for transfer of the nascent chain across the membrane. Depletion of the two components was performed by chromatography of detergent extracts on immunoaffinity supports. Detergent extracts lacking either SR or SSR were reconstituted and assayed for activity with respect to SR dependent elongation arrest release, nascent chain targeting, ribosome binding, secretory precursor translocation, and membrane protein integration. Depletion of SR resulted in the loss of elongation arrest release activity, nascent chain targeting, secretory protein translocation, and membrane protein integration, although ribosome binding was unaffected. Full activity was restored by addition of immunoaffinity purified SR before reconstitution of the detergent extract. Surprisingly, depletion of SSR was without effect on any of the assayed activities, indicating that SSR is either not required for translocation or is one of a family of functionally redundant components. PMID- 1313439 TI - Glycerol shock treatment facilitates purification of herpes simplex virus. AB - We describe an improved method for purification of herpes simplex virus. The primary improvement is the use of glycerol shock treatment to lyse infected cells. This is a rapid and simple technique that efficiently extracts the cytoplasm from the nucleus, while preserving nuclear integrity. Nearly 100% cell lysis is achieved by this method, and cytoplasmic virus yield is optimal. Other improvements to increase virus yield and purity and to economize on equipment are described. PMID- 1313438 TI - Low density lipoprotein receptor and cation-independent mannose 6-phosphate receptor are transported from the cell surface to the Golgi apparatus at equal rates in PC12 cells. AB - Efficient transport of cell surface glycoproteins to the Golgi apparatus has been previously demonstrated for a limited number of proteins, and has been proposed to require selective sorting in the endocytic pathway after internalization. We have studied the endocytic fate of several glycoproteins that accumulate in different organelles in a variant clone of PC12, a regulated secretory cell line. The cation-independent mannose 6-phosphate receptor and the low density lipoprotein receptor, both rapidly internalized from the cell surface, and the synaptic vesicle membrane protein synaptophysin, were transported to the Golgi apparatus with equivalent, nonlinear kinetics. Transport to the Golgi apparatus (t1/2 = 2.5-3.0 h) was several times faster than turnover of these proteins (t1/2 greater than or equal to 20 h), indicating that transport of these proteins to the Golgi apparatus occurred on average several times for each protein. In contrast, Thy-1, a protein anchored in the membrane by a glycosylphosphoinositide group, was internalized and transported to the Golgi apparatus more slowly than the three transmembrane proteins. Since each of the transmembrane proteins studied showed the same t1/2 for transport to the Golgi apparatus, we conclude that transport of these proteins from the cell surface to the Golgi apparatus does not require sorting information specific to any one of these proteins. These results suggest that one of the functions of late endosomes is constitutive recycling of cell surface receptors through the Golgi apparatus if they fail to recycle to the cell surface directly from early endosomes, and that the late endosome recycling pathway is followed frequently by many rapidly internalized proteins. PMID- 1313440 TI - Expression of myosin heavy and light chains and phosphorylation of the phosphorylatable myosin light chain in the heart ventricle of the European hamster during hibernation and in summer. AB - We investigated the expression of myosin subunits (myosin heavy chains) as well as light chains and the in vivo phosphorylation of the phosphorylatable myosin light chain in the heart ventricle of the adult male European hamster (Cricetus cricetus L.). Two myosin heavy chain isoenzymes could be detected under native and denaturing electrophoretic conditions having high (alpha-myosin heavy chain) and low (beta-myosin heavy chain) enzymatic activity. Enzymatic activity of alpha and beta-myosin heavy chain revealed a different temperature dependency. When temperature increased ATPase activity of the alpha-myosin heavy chain isoenzyme increased relatively more than ATPase activity of the beta-myosin heavy chain isoenzyme. Summer animals expressed predominantly the beta-myosin heavy chain (79% of total myosin) while during hibernation the alpha-myosin heavy chain expression increased to 53% of total myosin. Winter-active hamsters kept at 22 degrees C and 12 h day/night rhythm showed the same myosin heavy chain isoenzyme pattern as summer-active animals. Two myosin light chain forms were expressed in the ventricle of all animal groups. The in vivo phosphorylation level of the phosphorylatable myosin light chain decreased from 45% in summer-active hamster to 23% during hibernation. PMID- 1313442 TI - Relaxant effect of phalloidin on Triton-skinned microvascular and other smooth muscle preparations. AB - Guinea pig mesenteric microarteries (diameter 60-100 microns), the main branch of the mesenteric artery and taenia coli were skinned with 1% Triton X-100 for 4 h at 4 degrees C. Microarteries, mounted for circumferential force measurement, developed maximal active force in response to elevation of the free Ca2+ (pCa = 4.52, in EGTA buffer) in the presence of ATP (7.5 mM) and calmodulin (0.1-0.3 microM). In these preparations, addition of phalloidin (1-100 microM) slowly (greater than 1 h) relaxed submaximal contractions (pCa greater than 4.52) in a dose-dependent manner. Relaxation was irreversible as, after phalloidin wash-out, subsequent active force to pCa = 4.52 was also reduced. By contrast, phalloidin preincubation and wash-out under relaxed conditions (pCa greater than 8) only reduced subsequent force to pCa = 4.52 on prolonged stimulation. The extent of phalloidin-induced relaxation was not dependent on free Ca2+ between pCa 6.40 and 4.52. Phalloidin-induced relaxation did not occur during rigor contractions (i.e. absence of ATP and Ca2+). These mechanical effects of phalloidin were accompanied by a decreased leak of actin out of the skinned preparations and by the prevention of guanidine extraction of actin from these preparations. Phalloidin did not inhibit the myosin light chain kinase or phosphatase activity isolated from these preparations. In addition, the relaxant effects were also noted in taenia coli and the main branch of the mesenteric artery but not in skinned porcine ventricular heart muscle. These experiments suggest the possible participation of actin filament dynamics on the maintenance of active force in Triton-skinned smooth muscle. PMID- 1313441 TI - Ion conduction and discrimination in the sarcoplasmic reticulum ryanodine receptor/calcium-release channel. PMID- 1313443 TI - Isoform-specific regulation of platelet-derived growth factor activity and binding in osteoblast-enriched cultures from fetal rat bone. AB - In osteoblast-enriched cultures from fetal rat bone, the A-chain homodimer of platelet-derived growth factor (PDGF-AA) is less potent than the PDGF isoforms containing B chain subunits (PDGF-AB and PDGF-BB), but normal osteoblasts appear to synthesize only PDGF-A subunit mRNA and polypeptide. However, other agents may regulate PDGF-AA activity in skeletal tissue. Pretreatment of osteoblast-enriched cultures with interleukin 1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF-alpha) synergistically enhanced the mitogenic effect of PDGF-AA coincident with increased binding site occupancy, but neither factor augmented PDGF-BB activity or binding. Polyacrylamide gel analysis showed 125I-PDGF-AA binding complexes predominantly at greater than 200 kD and faint labeling at 185 kD. After IL-1 alpha or TNF-alpha pretreatment, PDGF-AA binding increased at both sites, but this effect was more striking at 185 kD, which co-migrated with 125I PDGF-BB-labeled complexes. PDGF-AA binding sites were rapidly lost by comparison to those for PDGF-BB in cycloheximide-treated cultures, but they remained relatively enhanced by IL-1 alpha and TNF-alpha pretreatment. These studies indicate that IL-alpha and TNF-alpha increase PDGF-AA binding and activity for osteoblasts by mechanisms that are at least in part independent of new receptor synthesis, and suggest regulatory events that could control how PDGF binding sites specifically recognize different ligands. PMID- 1313444 TI - Direct contact between sympathetic neurons and rat cardiac myocytes in vitro increases expression of functional calcium channels. AB - To test the hypothesis that direct contact between sympathetic neurons and myocytes regulates expression and function of cardiac Ca channels, we prepared cultures of neonatal rat ventricular myocytes with and without sympathetic ganglia. Contractile properties of myocytes were assessed by an optical-video system. Contractility-pCa curves showed a 60% greater increase in contractility for innervated myocytes compared with control cells at 6.3 mM [Ca]0 (n = 8, P less than 0.05). Cells grown in medium conditioned by growth of ganglia and myocytes were indistinguishable physiologically from control cells. [Bay K 8644] contractility curves revealed a 60 +/- 10% enhancement of the contractility response at 10(-6) M for innervated cells compared with control cells. The increased response to Bay K 8644 was not blocked by alpha- or beta-adrenergic antagonists. Moreover, increased efficacy of Bay K 8644 was maintained for at least 24 h after denervation produced by removal of ganglia from the culture. Dihydropyridine binding sites were assessed with the L channel-specific radioligand 3[H]PN200-110. PN200-110 binding sites were increased by innervation (51 +/- 5 to 108 +/- 20 fmol/mg protein, P less than 0.01), with no change in KD. Peak current-voltage curves were determined by whole-cell voltage clamp techniques for myocytes contacted by a neuron, control myocytes, and myocytes grown in conditioned medium. Current density of L-type Ca channels was significantly higher in innervated myocytes (10.5 +/- 0.4 pA/pF, n = 5) than in control myocytes (5.9 +/- 0.3 pA/pF, n = 8, P less than 0.01) or myocytes grown in conditioned medium (6.2 +/- 0.2 pA/pF, n = 10, P less than 0.01). Thus, physical contact between a sympathetic neuron and previously uninnervated neonatal rat ventricular myocytes increases expression of functional L-type calcium channels as judged by contractile responses to Ca0 and Bay K 8644, as well as by electrophysiological and radioligand binding properties. PMID- 1313445 TI - Intravascular filarial parasites inhibit platelet aggregation. Role of parasite derived prostanoids. AB - The nematode parasites that cause human lymphatic filariasis survive for long periods in their vascular habitats despite continual exposure to host cells. Platelets do not adhere to blood-borne microfilariae, and thrombo-occlusive phenomena are not observed in patients with circulating microfilariae. We studied the ability of microfilariae to inhibit human platelet aggregation in vitro. Brugia malayi microfilariae incubated with human platelets caused dose-dependent inhibition of agonist-induced platelet aggregation, thromboxane generation, and serotonin release. As few as one microfilaria per 10(4) platelets completely inhibited aggregation of platelets induced by thrombin, collagen, arachidonic acid, or ionophore A23187. Microfilariae also inhibited aggregation of platelets in platelet-rich plasma stimulated by ADP, compound U46619, or platelet activating factor. The inhibition required intimate proximity but not direct contact between parasites and platelets, and was mediated by parasite-derived soluble factors of low (less than 1,000 Mr) molecular weight that were labile in aqueous media and caused an elevation of platelet cAMP. Prior treatment of microfilariae with pharmacologic inhibitors of cyclooxygenase decreased both parasite release of prostacyclin and PGE2 and microfilarial inhibition of platelet aggregation. These results indicate that microfilariae inhibit platelet aggregation, via mechanisms that may include the elaboration of anti-aggregatory eicosanoids. PMID- 1313446 TI - Cyclic nucleotides attenuate thrombin-evoked alterations in parameters of platelet Na/H antiport. The role of cytosolic Ca. AB - In this work, we explored the role of cyclic nucleotides in modulating parameters of the Na/H antiport in human platelets. Sodium nitroprusside and iloprost, as well as cyclic nucleotide analogues, were used to raise cellular levels of cAMP and cGMP. Cyclic nucleotides reversed the thrombin-evoked alkaline shift in cytosolic pH set point and the activity of the Na/H antiport, concurrently with attenuation of thrombin-induced rise in cytosolic free Ca. No effect of cyclic nucleotides was observed in platelets not treated with thrombin, or platelets subjected to phorbol 12-myristate 13-acetate. cAMP did not reverse ionomycin induced changes in the parameters of the Na/H antiport. Collectively, these observations indicate that cyclic nucleotides modulate the Na/H antiporter in human platelets through their effect on thrombin-evoked changes in cytosolic free Ca. Presumably, this effect holds for other agonists which stimulate phospholipase C, raise cytosolic-free Ca, and activate the Na/H antiport through protein kinase C dependent and protein kinase C-independent mechanisms. PMID- 1313447 TI - Beta-adrenergic upregulation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells. AB - We used the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6') carboxyfluorescein to monitor the recovery of the intracellular pH (pHi) of rat parotid acini from an NH4(+)-induced alkaline load. This recovery was markedly inhibited by the loop diuretic bumetanide and by Cl- removal, indicating that it is largely due to NH4+ entry via the basolateral Na(+)-K(+)-2Cl- cotransporter. The rate of recovery of pHi was enhanced threefold by pretreatment (37.5 s) with isoproterenol (K1/2 = 21.5 nM) or norepinephrine (in the presence of phentolamine), and blocked by the beta 1-specific antagonist atenolol, indicating an upregulation of cotransport activity by beta 1-adrenergic stimulation. The effect of isoproterenol was prevented by protein kinase inhibitors and mimicked by cAMP analogues, and by maneuvers known to increase cytosolic cAMP levels in these cells, consistent with the involvement of protein kinase A. Physiologically, such an upregulation of the acinar Na(+)-K(+)-2Cl- cotransporter would lead to an increase in acinar chloride uptake across the basolateral membrane, and consequently, an increase in overall chloride and fluid secretion. Prevention of this upregulation by beta-blockers and possibly by other commonly used clinical agents may account for the dry mouth and dry eyes experienced by some patients taking these medications. PMID- 1313448 TI - cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. AB - Adenosine 3',5'-cyclic monophosphate stimulates chloride (Cl-) secretion across airway epithelia. To determine whether cAMP also stimulates HCO3- secretion, we studied cultured canine and human airway epithelial cells bathed in a HCO3-/CO2 buffered, Cl(-)-free solution. Addition of forskolin stimulated an increase in short-circuit current that was likely a result of bicarbonate secretion because it was inhibited by a HCO3(-)-free solution, by addition of the carbonic anhydrase inhibitor, acetazolamide, or by mucosal addition of the anion channel blocker, diphenylamine 2-carboxylate. The current was dependent on Na+ because it was inhibited by removal of Na+ from the submucosal bathing solution, by addition of the Na+ pump inhibitor, ouabain, or by addition of amiloride (1 mM) to the submucosal solution. An increase in cytosolic Ca2+ produced by addition of a Ca2+ ionophore also stimulated short-circuit current. These data suggest that cAMP and Ca2+ stimulate HCO3- secretion across airway epithelium, and suggest that HCO3- leaves the cell across the apical membrane via conductive pathways. These results may explain previous observations that the short-circuit current across airway epithelia was not entirely accounted for by the sum of Na+ absorption and Cl- secretion. The cAMP-induced secretory response was absent in cystic fibrosis (CF) airway epithelial cells, although Ca(2+)-stimulated secretion was intact. This result suggests that HCO3- exist at the apical membrane is through the Cl- channel that is defectively regulated in CF epithelia. These results suggest the possibility that a defect in HCO3- secretion may contribute to the pathophysiology of CF pulmonary disease. PMID- 1313450 TI - Autoantibodies to the ribosomal P proteins react with a plasma membrane-related target on human cells. AB - Autoantibodies to ribosomal P-proteins are present in 12-16% of patients with systemic lupus erythematosus and are associated with neuropsychiatric disease. As the ribosomal P proteins are located in the cytoplasm, the pathogenic effects of their cognate autoantibodies are unclear. In this study affinity-purified anti-P autoantibodies were used to explore the cell surface of several types of human and animal cells. Immunofluorescence as well as EM immunogold analysis demonstrated, on the surface of human hepatoma cells, the presence of an epitope that is antigenically related to the immunodominant carboxy terminus of P proteins. The presence of this epitope was also demonstrated on the surface of human neuroblastoma cells and, to a lesser extent, on human fibroblasts. Furthermore, the Western blot technique revealed in purified human and animal plasma membranes a 38-kD protein that is closely related or identical with ribosomal P0 protein. The availability of reactive P peptide on the surface of cells makes possible the direct effect of autoantibodies on the function and viability of cells that express this antigenic target. This delineates one of the possible impacts of anti-P antibodies in disease expression. PMID- 1313449 TI - Preferential mRNA expression of prostromelysin relative to procollagenase and in situ localization in human articular cartilage. AB - An imbalance between extracellular proteinases and their inhibitors is thought to underlie cartilage degradation. In cultures of adult cartilage, prostromelysin mRNA levels were much higher than those for procollagenase and this differential was increased in cultures stimulated with IL-1 beta. Analysis of mRNA prepared from freshly isolated chondrocytes showed abundant amounts of prostromelysin mRNA in normal adult cartilage but low levels in the neonate. Not all adult cartilage may possess such high levels of prostromelysin mRNA, as the message levels in the cartilage remaining on late-stage osteoarthritic joints were lower than those in normal adult cartilage. Relative to prostromelysin mRNA, little procollagenase and TIMP mRNA were found in the adult cartilage. In situ hybridization revealed that metalloproteinase mRNAs were localized in chondrocytes of the superficial zone in adult cartilage. However, upon IL-1 beta treatment, chondrocytes in all cartilage zones were observed to express prostromelysin mRNA. Relative to the neonate, the normal adult cartilage appears to have a high degradative potential, if one accepts that steady-state mRNA levels reflect prostromelysin production. As the adult cartilage is not apparently undergoing rapid turnover, it would appear that control of prostromelysin activation may be the major regulatory step in stromelysin-induced cartilage degradation. PMID- 1313452 TI - Cloned platelet thrombin receptor is necessary for thrombin-induced platelet activation. AB - Platelet activation by thrombin is critical for hemostasis and thrombosis. Structure-function studies with a recently cloned platelet thrombin receptor suggest that a hirudin-like domain in the receptor's extracellular amino terminal extension is a thrombin-binding determinant important for receptor activation. We now report that a peptide antiserum to this domain is a potent and specific antagonist of thrombin-induced platelet activation. This study demonstrates that the cloned platelet thrombin receptor is necessary for platelet activation by thrombin, and provides a strategy for developing blocking monoclonal antibodies of potential therapeutic value. PMID- 1313453 TI - Reinfection of liver graft by hepatitis C virus after liver transplantation. AB - We have investigated hepatitis C virus (HCV) viremia before and after orthotopic liver transplantation (OLT). 38 patients were examined; 16 were anti-HCV positive and 22 anti-HCV negative pre-OLT in a RIBA-2 test (Ortho Diagnostic Systems Inc., Westwood, MA). HCV-RNA was detected using a modified nested polymerase chain reaction in 14/38 and 10/38 patients before and after OLT, respectively. 7 of these 14 subjects who were HCV-RNA positive before OLT were also positive for serum hepatitis B surface antigen. After OLT, six patients became HCV-RNA positive, likely as a result of transfusions, while four developed a probable recurrence of HCV infection. Infection of the liver graft by the same strain of HCV was indeed demonstrated by sequence analysis of a hypervariable domain (in the envelope region) in two cases. This establishes the possibility of HCV recurrence and shows the usefulness of polymerase chain reaction as the only assay currently capable of identifying HCV infection after OLT. PMID- 1313451 TI - Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex. AB - Studies were undertaken in Munich-Wistar rats to assess the influence of changes in filtered bicarbonate (FLHCO3), induced by changes in GFR, on Na+/H+ exchange activity in renal brush border membrane vesicles (BBMV). Whole-kidney and micropuncture measurements of GFR, FLHCO3, and whole-kidney and proximal tubule HCO3 reabsorption (APRHCO3) were coupled with BBMV measurements of H+ gradient driven 22Na+ uptake in each animal studied. 22Na+ uptake was measured at three Na+ concentration gradients to allow calculation of Vmax and Km for Na+/H+ exchange. GFR was varied by studying animals under conditions of hydropenia, plasma repletion, and acute plasma expansion. The increase in GFR, FLHCO3, and APRHCO3 induced by plasma administration correlated directly with an increase in the Vmax for Na+/H+ exchange in BBMV. The Km for sodium was unaffected. In the plasma-expanded rats, the Vmax for Na+/H+ exchange was 22% greater than in the hydropenic rats (P less than 0.025) whereas APRHCO3 was 86% greater (P less than 0.001). These results indicate that increases in FLHCO3, induced by acute increases in GFR, stimulate Na+/H+ exchange activity in proximal tubular epithelium. This stimulation is a mechanism which can, in part, account for the delivery dependence of proximal bicarbonate reabsorption. PMID- 1313454 TI - Synchronous squamous and glandular neoplasia of the anal canal. AB - A 48 year old man presented with invasive adenocarcinoma in the wall of a non healing anal fistula. The subsequent abdomino-perineal resection specimen showed residual invasive carcinoma coexisting with in situ carcinoma of anal glands as well as in situ squamous carcinoma of the anal canal. The epithelium of the anal canal had koilocytotic features. DNA hybridisation studies by the dot blot technique showed weak positivity for human papillomavirus (HPV) subtypes 16, 18. This case illustrates a number of important points--namely, anal fistulas, particularly non-healing fistulas should be biopsied to exclude malignancy; some adenocarcinomas of the anal arise in anal glands; the coexistence of glandular and squamous carcinoma with evidence of HPV infection is highly reminiscent of similar synchronous lesions of the uterine cervix and suggests that HPV may have an aetiological role in both squamous and glandular carcinomas of the anal canal. PMID- 1313455 TI - Primary biphasic synovial sarcoma of the orbit. AB - Synovial sarcoma is one of the most common soft tissue malignancies of adolescents and young adults. Despite its name, it is no longer thought to be histogenetically derived from the synovium. What seems to be the first case of synovial sarcoma to arise in the orbit presented in a 21 year old woman as a slowly enlarging subconjunctival mass. Although this tumour was typically biphasic, the monophasic spindle cell variant arising at this site could easily be confused with less aggressive orbital connective tissue neoplasms. PMID- 1313456 TI - Chicken pox infection (varicella zoster virus) and acute monoarthritis: evidence against a direct viral mechanism. AB - A 9 year old boy developed acute monoarthritis of the left knee concurrent with the appearance of a varicella zoster virus (VZV) rash. Repeated VZV DNA hybridisation of the cells within the synovial fluid and synovial membrane failed to show any evidence of intracellular virus. Virus was isolated from synovial fluid 24 hours after the start of clinical infection but not later. These findings suggest that the mechanism of the arthritis is not due to viral replication inside the swollen joint. PMID- 1313457 TI - Epstein-Barr virus and Hodgkin's disease. PMID- 1313458 TI - Absence of human papillomavirus in cervical adenocarcinoma. PMID- 1313459 TI - Clinical efficacy of a low abrasive dentifrice for the relief of cervical dentinal hypersensitivity. AB - 2 strontium chloride hexahydrate-containing dentifrices (SCH), similar except for their respective abrasive systems, were compared in a 2-month randomised double blind parallel clinical study to evaluate their comparative effectiveness in terms of cervical dentinal hypersensitivity. 2 groups of 20 subjects, each with cervical dentinal hypersensitivity, were evaluated for tactile sensitivity by Yeaple probe, air sensitivity using a dental air syringe and subjective perception of pain by means of a visual analogue scale. There was no difference between the dentifrices as regards reduction of cervical dentinal hypersensitivity at each time point. The response to both dentifrices was evident within 4 weeks of use and the degree of improvement increased throughout the 8 week study period. The results support the conclusion that changing the abrasive component of SCH dentifrices did not significantly increase or decrease the (desensitizing) activity of the original product. PMID- 1313460 TI - Pathogenicity and antigen detection of the Nouzilly strain of transmissible gastroenteritis coronavirus, in 1-week-old piglets. AB - We compared the pathogenicity and the sites of multiplication of the attenuated Nouzilly strain, with the highly passaged Purdue-115 and the virulent Gep II strains of transmissible gastroenteritis (TGE) coronavirus, in 1-week-old weaned piglets. The immunohistochemical peroxidase technique, with an antiviral nucleoprotein monoclonal antibody, was used for the localization of the multiplication sites, in the intestine and other organs. The Gep II and the Purdue-115 strains, administered orally to piglets, caused clinical signs and lesions of TGE. These strains multiplied within the intestinal tract in the enterocytes of the jejunum and ileum, Peyer's patches and mesenteric lymph nodes. In view of the small numbers of infected cells in the tonsils, spleen, kidney, liver and lung, these tissues are not considered to be preferential multiplication sites. The attenuated Nouzilly strain multiplies only in the ileum and the mesenteric lymph nodes. The variation in the tropism for particular parts of the intestine (with the preferential localization of the virus in the ileum rather than the jejunum), could be related to the high degree of attenuation of the Nouzilly strain. PMID- 1313461 TI - Increased superoxide anion release by peritoneal macrophages in mice with a chronic infection of lactic dehydrogenase virus. AB - The function of macrophages in mice chronically infected by lactic dehydrogenase virus (LDV) was studied. Superoxide anion (O2-) release was examined by using peritoneal macrophages. O2- release increased markedly from 3 weeks to 12 months, but not at 1 week post infection. O2- release was 1.2 to 1.5 times greater than in uninfected mice. Increased O2- release from macrophages in LDV-infected mice may explain, at least in part, suppressive effects on tumour growth seen in the chronic phase of infection. PMID- 1313462 TI - A statistical approach to the ecology of Porphyromonas gingivalis. AB - Previous studies have suggested that infections with Porphyromonas gingivalis, associated with periodontal disease, may consist of one clonal type. It has also been shown that each individual patient carries a unique clonal type of P. gingivalis, as assessed by DNA fingerprinting. This issue was further examined by random collection of multiple isolates of P. gingivalis from multiple sites in several patients, and characterization of these isolates by DNA fingerprinting. Although most patients appeared to be infected exclusively by one clonal type of P. gingivalis, at least one patient was found to harbor two distinct clonal types. This indicates that the simultaneous presence of different clonal types of P. gingivalis can occur. A statistical method was developed for retrospective analysis of these data for estimation of whether the remainder of these patients were actually infected with single or multiple clonal types of P. gingivalis. With this statistical method, a confidence interval was calculated for estimation of the true proportion of a single observed clonal type in the potential population of P. gingivalis that might be recovered from an infected patient. Statistically, the sampling of small numbers of sites per patient or isolates per site leads to a wide confidence interval for the estimated true proportion of the observed clonal type in the infecting P. gingivalis population. For example, when five sites in an oral cavity yield indistinguishable P. gingivalis isolates, then the true proportion of this clonal type in the total P. gingivalis population in the infected oral cavity is estimated to be in the interval between 55% and 100% (at a 95% confidence level).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1313463 TI - Manifestations of intense noise stimulation on spontaneous otoacoustic emission and threshold microstructure: experiment and model. AB - Comparison between changes that occur simultaneously on spontaneous otoacoustic emissions (SOAEs) and on other cochlear origin phenomena can contribute to the understanding of cochlear micromechanical activity. The temporary changes that arise after short noise exposure are investigated in the following paper. The effects of noise exposure on the threshold microstructure near an SOAE and on the amplitude and frequency of the SOAE were measured. These experimental results indicate the following: (1) exposure to wideband noise for a short time causes a temporary reduction in the SOAE frequency and amplitude, and alters reversibly the threshold microstructure in the vicinity of the SOAE. The difference between the minimum and maximum in the threshold microstructure is reduced, and the frequency that yields the minimum threshold decreases; (2) the threshold at the SOAE frequency is most sensitive to noise exposure; (3) intense stimulation causes a relatively small increase, or even a decrease, in threshold at frequencies near the SOAE. The experimental results are interpreted in terms of a nonlinear transmission line model which includes nonlinear amplifiers. The effect of the noise exposure is modeled by reduction in the cochlear partition amplification term. Most of the experimental results are predicted by this model. PMID- 1313464 TI - Stabilization of perceived echo amplitudes in echolocating bats. I. Echo detection and automatic gain control in the big brown bat, Eptesicus fuscus, and the fishing bat, Noctilio leporinus. AB - Previous research on echo detection in bats has suggested that the effective threshold is a function of the acoustic clutter in the experimental environment, as might be expected given the low ambient noise levels typical of such psychophysical research. This paper demonstrates that theory of signal detectability (TSD) methodology is applicable to bats and uses it to show that an important element of clutter limiting in Eptesicus fuscus and Noctilio leporinus is backward masking of phantom targets by the real echo from the loudspeakers used to generate them. This information suggests that a previous estimate of the magnitude of automatic gain control (AGC) is too high, due to variable backward masking inherent in the experimental method used. A re-examination of gain control using a masking-free method shows that it reduces auditory sensitivity by 6 to 7 dB per halving of target range, rather than 11 dB as previously thought. PMID- 1313465 TI - Bayesian model selection and minimum description length estimation of auditory nerve discharge rates. AB - Auditory-nerve fiber discharges are modeled as self-exciting point processes with intensity given by the product of a stimulus-related function and a refractory related function. Previous methods of estimating these two functions, based on the maximum-likelihood principle, have the problem of estimating more parameters than the data can support. A new procedure, based on a Bayes criterion for choosing the complexity of the model in addition to estimating the parameters, solves the over-parametrization problem. This procedure is seen to relate asymptotically to Rissanen's minimum description length (MDL) criterion. A performance comparison of the MDL procedure with previous maximum-likelihood algorithms promotes the adoption of the MDL procedure for simultaneous estimation of the stimulus and recovery properties of auditory-nerve discharge. PMID- 1313466 TI - Nutrition and behavioral characteristics and determinants of plasma cholesterol levels in men and women. AB - The National Cholesterol Education Program advocates dietary interventions in persons with high and moderate blood cholesterol levels and in the general population as a preventive measure for coronary heart disease. For these efforts to be successful, it is necessary to understand consumer characteristics and behaviors, including nutrient intake and dietary patterns. We studied the relationship of plasma cholesterol levels to consumer characteristics and dietary behaviors by examining 127 men (aged 20 through 71 years) and 187 women (aged 18 through 67 years) as part of a cholesterol screening project in the administrative offices and academic departments of Boston University from March 1988 through June 1988. Our results showed that specific consumer characteristics and dietary behaviors significantly differentiated male and female groups with low, moderate, and high cholesterol levels. Factors that should be considered in planning dietary interventions aimed at cholesterol reduction in men include spouse involvement and support in lipid-lowering interventions; weight reduction; increase in exercise; reduction in beef intake; and increases in dietary fiber and carbohydrates, particularly fruits. For women, recommendations include weight reduction; possible interventions aimed at reducing blood pressure (ie, behavioral modification aimed at reducing stress, increasing exercise, and cooking low-salt meals); reduction in beef intake, dietary fat, and saturated fat; and increases in carbohydrates and dietary fiber. PMID- 1313467 TI - Oat bran lowers plasma cholesterol levels in mildly hypercholesterolemic men. AB - The effects of oat bran and wheat bran on plasma lipid concentrations were compared in a crossover study. Each bran (123 g oat bran or 54 g wheat bran) added nearly 18 g of nonstarch polysaccharide to a background diet containing about 10 g nonstarch polysaccharide. Twenty-three men (average plasma cholesterol level = 5.84 mmol/L, and low-density-lipoprotein (LDL) cholesterol level = 4.11 mmol/L) were randomly assigned to either the oat or wheat bran diet for 4 weeks and then changed to the alternate bran diet for a similar period. The oat bran diet produced significantly lower levels of plasma total cholesterol and LDL cholesterol: 5.65 +/- 0.16 and 3.88 +/- 0.15 mmol/L (mean +/- standard error) for oat bran vs 5.89 +/- 0.16 and 4.11 +/- 0.16 mmol/L for wheat bran. Food intake diaries showed that average consumption of total fat and saturated fat was identical during the two test periods, which excluded displacement of fat as an explanation for lowering of plasma cholesterol by oat bran. Our results indicate that in mildly hypercholesterolemic men, a diet high in soluble oat fiber can significantly lower plasma total cholesterol and LDL cholesterol and thus potentially lower the risk of coronary heart disease.